The Effect of Decentralized Services on Multidrug-Resistant Tuberculosis Care in Sub- Saharan Africa: A Systematic Review

The Effect of Decentralized Services on Multidrug-Resistant Tuberculosis Care in Sub- Saharan Africa: A Systematic Review | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The Effect of Decentralized Services on Multidrug-Resistant Tuberculosis Care in Sub- Saharan Africa: A Systematic Review Meckie Achayo, Yaw-Awuku Larbi, Sumaya Mall, Latifat Ibisomi This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2077078/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Multidrug-resistant tuberculosis (MDR-TB), which is resistant to rifampicin and isoniazid, is a significant public health concern. MDR-TB care has transitioned from being centralized where inpatient care provided at specialized facilities to being decentralized, where the focus is on outpatient care provided at the community. This review aims to synthesize results of studies on the effect of decentralizing MDR- TB care on the accessibility of services and patient treatment outcomes in sub- Saharan Africa (SSA). Methods A systematic review which synthesized observational studies, interrupted time series and cost analyses from SSA, published between 2011 and 2021 was conducted. Five databases (PubMed, Cochrane library, Global health, Scopus and Global Index Medicus (WHO)) were searched to identify eligible studies. Quality assessment of included studies was conducted using the Effective Public Health Practice Project (EPHPP) tool for observational studies and the CHEERS checklist for cost evaluation studies. Results Twelve studies met the eligibility criteria for inclusion. In SSA, decentralization of MDR-TB care has been suggested to improve utilization and cost of MDR-TB services. The treatment cost has reduced and volume of patients utilizing both diagnostic and treatment services has increased in all countries represented by the studies. Increased successful treatment as well as reduction in patients who are lost to follow up have also been suggested to be outcomes of decentralizing MDR-TB treatment services within SSA. Conclusion In resource limited settings such as those in SSA, studies have suggested that decentralizing MDR-TB services is beneficial as it enables increased utilization of diagnostic and treatment services at lower service delivery costs. High retention into care and treatment success rates are also suggested to be better achieved and maintained when using decentralized approaches than centralized approaches. Multidrug-resistant tuberculosis Centralized MDR-TB care Decentralized MDR-TB care Access to MDR-TB services Figures Figure 1 Background Tuberculosis (TB), an airborne disease caused by Mycobacterium tuberculosis , has been a global health concern for many decades. 1 The World Health Organization (WHO)’s 2020 Global report on TB estimated 10 million new TB cases, and 1.2 million deaths. 2 Since the early 1990s, the emergence of multidrug-resistant strains of TB (MDR-TB) [1] , has challenged TB control programmes worldwide. 1,3–6 The estimated incidence of MDR-TB was reported to be 465,000 cases, which is a combined total of 3.3% of new TB cases and 18% of previously treated TB cases. 2 The African region ranked third in the incidence of MDR-TB in 2019 globally, with 17% of all reported cases. 2 Programmatic management of MDR-TB has transitioned from a centralized to a decentralized care model. A centralized model is one whereby, MDR-TB patients are treated as inpatients in designated, specialized DR-TB treatment facilities. 7 In this model, patients are usually treated by specialized provider(s) throughout the intensive phase of treatment or until negative diagnostic results (through culture or smear conversion). 7 While this approach allows easier monitoring of patients’ adherence to medication and adverse events, it is not without limitations. 8,9 Among the limitations of this approach are; delays in treatment initiation due to insufficient bed capacities, limited human resources to deliver care and increased socioeconomic costs associated with hospitalization. 10 Also, centralized facilities are sometimes located far from patients’ homes necessitating patients to travel long distances to access services. 11 The situation is more marked in resource limited settings such as those of SSA. 9,12 As a result, in 2011, the WHO recommended decentralized care for MDR-TB. 13 Contrary to centralized care, decentralized MDR-TB care, is defined as management (treatment and care) of MDR-TB provided at the community where the patient resides. 9 This approach mainly incorporates ambulatory modes of care which can be defined as care provided on an outpatient basis. 7 Ambulatory care can be clinic-based where patients attend a peripheral clinic, or community-based which utilizes local health care workers (HCWs), former patients, co-workers, neighbours or family members to directly observe treatment without frequent visits to a health care facility. 12,13 Community-based care is also referred to as home-based mode of care. 13 Decentralized care for MDR-TB has been reported to improve access to MDR-TB diagnostic and treatment services. 10 Service affordability is the ability to pay for services without facing financial hardship. 14 It is an integral component to achieving universal access to health services. 14 It accounts for direct costs (e.g. price of health services), indirect costs (e.g. transportation to health facilities) and opportunity costs (e.g. taking time off work) of health services, including MDR-TB services. 14 To our knowledge no review has examined these costs as experienced by MDR-TB service providers (health system) and recipients of MDR-TB services (patients) in sub-Saharan Africa. The present review, focuses on access to services in terms of affordability and utilization of services as these areas fall short of the target set in the End TB Strategy and at the United Nations (UN) high-level meeting on TB in 2018, respectively. 2,19 The End TB Strategy, adopted in 2014, targeted that no household affected by TB faces catastrophic costs [2] by 2020. 2,19 However, pooled estimates published in 2022 show that more than 78% of MDR-TB affected households still face catastrophic costs. 20 In the UN meeting, a global target of treating 1.5 million people by 2022 was set. 2 By 2019, only 333,000 people (22% of target) had received treatment for MDR-TB globally. 2 In previous systematic reviews which compared MDR-TB treatment outcomes between centralized and decentralized approaches, only a handful of SSA countries were represented and none focused specifically on SSA. 9,10,22 To our knowledge, there has also been no systematic evaluation of the effect of decentralization on the accessibility of MDR-TB services since its recommendation. This review, therefore, aims to examine the effect of decentralizing MDR-TB care on access (in terms of utilization and cost) to services and patient treatment outcomes in sub-Saharan Africa. Findings from this study will elucidate the effect of decentralized approaches in MDR-TB care within the SSA context. Consequently, this could inform decision making processes to the adoption of decentralized approaches across the SSA region. [1] Multidrug-resistant tuberculosis (MDR-TB) is tuberculosis caused by Mycobacterium tuberculosis strains that exhibit resistance to both rifampicin and isoniazid. 7 [2] Catastrophic costs are defined as total costs equivalent to >20% of annual household income. 2 methods Setting s Sub-Saharan African region spans from the southern border of the Saharan Desert to the southern tip of the African continent. It is home to over 1.1 billion people, 42.3% of which live in extreme poverty (% population below $1.90 a day). 23–25 Thus, poverty, together with weak health systems characterised by inadequate diagnostic services, medical supplies and human resource capacities pose hindrances to the deployment and sustainability of MDR-TB interventions. 26 Further, nearly half (47%) of the urban residents in sub-Saharan Africa live in unimproved houses - houses with poor sanitation, poor water supply, uncompleted buildings and/or crowded houses with more than three people living in a single room. 27,28 These conditions have been shown to influence MDR-TB transmission and consequently increase the disease burden. 29 Study design The present systematic review was conducted and reported following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The PRISMA is a 27-item guideline developed to guide the reporting of systematic reviews and meta-analyses. 30 Eligibility criteria Eligibility criteria for studies included in the review are presented in Table 1 below. Table 1 : Table showing eligibility criteria for study selection Criteria Description Location The study had to have been conducted in a country or in countries that are within the sub-Saharan African region. All studies conducted in countries outside SSA, including northern African countries (Egypt, Libya, Algeria, Morocco, Tunisia and Western Sahara) were excluded from the review. Study design Interrupted time series, observational studies (prospective and retrospective cohort studies, case control studies and cross-sectional studies) and cost evaluation studies were included in the review. Studies with a qualitative and experimental design (e.g RCTs) were excluded from the review. Comparison groups The study should be comparing patients receiving decentralized (ambulatory or community-based) mode of care and those receiving a centralized mode of care for MDR-TB treatment. Decentralized MDR-TB care was considered to be one which is purely provided on an outpatient basis, from treatment initiation to completion. Also, for diagnostic services (e.g. laboratory services), decentralized care was one where diagnosis is done at facilities other than the central laboratory. Centralized MDR-TB care was considered to be care which is provided on an in-patient basis at designated specialized facilities by specialized providers. Outcomes The study should have reported at least one treatment outcome as per WHO standards, including, cure, completion, success, death, failure, default/lost to follow-up. Studies reporting the number of patients utilizing MDR-TB services, and/or cost of MDR-TB services were also included. All studies solely reporting treatment outcomes and/or cost for RR-TB, pre-XDR and XDR-TB, and not for MDR-TB, were excluded from the review. Data source Studies published in peer reviewed journals. Year of publication Between 2011 and 2021. This time period was selected because 2011 was the year when WHO recommended the decentralized approach and 2021 the year the study was conducted. Language of published study English. No other languages were included as none of the reviewers were proficient in either French, Portuguese or Arabic. Also, there was limited time for translation services. Search strategy Studies conducted within sub-Saharan Africa focusing on decentralized and centralized treatment approaches for MDR-TB were sourced from five scientific databases: PubMed, Global health, Cochrane library, Scopus and Global Index Medicus. The last search was conducted on January 28, 2021. Keywords that were used for the literature search are: “mdr-tb AND decentralization”, “mdr-tb AND community-based”, “mdr-tb AND ambulatory“, “mdr-tb AND sub-Saharan Africa”, “(mdr-tb AND decentralization) AND sub-Saharan country name ”, “(mdr-tb AND community-based) AND sub-Saharan country name ”, “(mdr-tb AND ambulatory) AND sub-Saharan country name ” A manual search of literature was also conducted using the reference lists of studies that had been identified. Study selection and data extraction Retrieved studies from database and bibliographic searches were managed using Mendeley referencing manager software (version 1.19.8). The software (Mendeley) was used to screen and remove duplicates. Thereafter, titles and abstracts of retrieved studies were screened and those unrelated to the review topic were removed. The remaining studies were read full text and those not matching the eligibility criteria were excluded. Justification for study exclusion was documented (Figure 1). Two reviewers (MA and YL) worked independently during study selection and met to compare their inclusions. Differences on the inclusion/exclusion of studies between the two reviewers were resolved by consensus. Figure 1. Flow diagram presenting the selection of studies on centralized and decentralized management of MDR-TB Key information extracted from each study included; first author’s name, year of publication, study design, study setting, description of centralized and decentralized models of care and outcome(s) measured. Other information extracted from studies when available included; sample size of control and intervention groups, number of patients utilizing MDR-TB services, number of samples tested for MDR-TB, cost of MDR-TB services and prevalence estimates of MDR-TB treatment outcomes such as treatment success, loss to follow-up, death and treatment failure. Data were extracted by MA and re-checked YL. Quality assessment Observational studies and interrupted time series designs The Effective Public Health Practice Project (EPHPP) tool was modified and used to assess the quality of observational studies (n=5) and interrupted time series (n=2). The EPHPP tool can be found as an additional file. The tool assesses six domains to establish the quality of a study. 31 However, one domain (blinding) was removed because it is a feature of experimental studies (eg RCTs) which were excluded from this study. Five domains, therefore, were used to establish the quality of these studies. The domains are; participant selection bias, design of study, confounding, data collection methods and withdrawals/dropouts. Each domain received a rating of being either weak (1 point), moderate (2 points) or strong (3 points). Scores from the domains were then added to derive a total score for each study. From the total score, an average score was calculated to get the global rating for a study. The minimum and maximum attainable global rating score per study was 1.00 and 3.00, respectively. Individual studies were then classified into either weak, moderate or strong categories depending on their global rating scores. Weak studies had a global rating score ranging between 1.00 – 1.50, moderate studies scored between 1.51 – 2.50 and strong studies obtained a score between 2.51 – 3.00. 31 The quality of six studies included in the review was classified as moderate and one study was classified as strong. No study was classified as weak. Economic evaluation studies The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) guideline was used for five studies that fall into this category. CHEERS is a 24-item checklist aimed at optimizing the reporting of health economic evaluations. 32 The checklist can be found as an additional file. For each item of the checklist, the page number and line to which the item is reported in each study were documented. Items which were not reported by studies and those which were not applicable to studies were also documented. Generally, the quality of reporting was good with three of the studies reporting all items that were applicable, one study reported all applicable items except two and the last study reported all but one applicable item. Results Study characteristics Twelve studies were eligible and included in this review ( Figure 1 ). Five studies were from the southern African region (South Africa), 11,33–36 two from the west African region (Nigeria) 37,38 and five from the east African region (Ethiopia (n=2), 39,40 Tanzania (n=1), 41 Uganda (n=1) 42 and Kenya (n=1) 43 ). Four of the included studies were cohort studies, 11,33,36,41 5 were cost analyses, 34,35,37–39 2 were interrupted time series 40,42 and one was a cross sectional study 43 ( Table 2 ). For the centralized model; 10 studies reported MDR-TB diagnosis and treatment at centralized hospitals, one study reported specimen diagnosis at a central laboratory and one study reported limited access (35% access) to diagnostic services during a scale-up project. For the decentralized model, 9 studies reported on MDR-TB treatment. The studies involved various treatment models such as ambulatory clinic-based model, home-based treatment and community-based treatment by mobile healthcare providers. One study reported specimen diagnosis at regional laboratories, one reported expanded access (>90% access) to diagnostic services during a scale-up project and one reported expansion of diagnostic services to peripheral facilities (Table 2). Utilization of MDR-TB services was reported by four studies. 40–43 Two of these reported utilization of treatment services alone, 41,42 one reported utilization of diagnostic services 43 alone and one reported utilization of both diagnostic and treatment services. 40 Five studies reported costs for MDR-TB care. 34,35,37–39 Of the five studies that reported treatment outcomes, all but one reported on treatment success. Lost to follow up, death and treatment failure were reported by all five studies ( Table 2 ). Table 2. Table showing characteristics of studies on decentralized versus centralized care of MDR-TB in Sub-Saharan Africa Author and year of publication Country Study design Year of intervention Sample size for control/intervention Description of models of care Timing of intervention Outcome(s) measured Centralized (Control) Decentralized (Intervention) Loveday et al, 2015 South Africa Prospective cohort 2008 - 2010 813/736 Treatment at a specialized central hospital Treatment at a rural hospital followed by outpatient clinic or home-based care Concurrent Treatment outcomes (cure, completion, success, failure, default, death, unsuccessful, transferred out) Sharma et al, 2015 Kenya Cross-sectional 2012 - 2013 355/432 Hospitals referring specimens to a central laboratory Hospitals referring specimens to a regional laboratory Concurrent Number and proportion of retreatment cases tested; event time when testing retreatment cases in reference laboratory Loveday et al, 2012 South Africa Prospective cohort 2008 - 2009 441/419 Treatment at a centralized specialist hospital followed by outpatient visits at the same facility Treatment at district hospitals followed by outpatient follow-ups by healthcare workers Concurrent Proportion of patients who culture converted; time-to-conversion, treatment-initiation-delay, survival Molla et al, 2017 Ethiopia Interrupted time series 2012 - 2015 56/790 Hospital-based care Ambulatory-based care Consecutive Access to MDR-TB service (number of TICs established, number of MDR-TB patients enrolled to treatment); treatment outcomes (cured, completed, failed, lost to follow up, died) 662/14,361 Diagnosis at centralized MDR-TB diagnostic centres (two culture centres, no GeneXpert centre) Diagnosis at decentralized MDR-TB diagnrostic centres (5 culture and DST centres, 49 GeneXpert centres) Consecutive Access to MDR-TB service (number of samples tested) Kasozi et al, 2020 Uganda Interrupted time series 2013 - 2017 41/1311 Treatment at specialized facilities Treatment initiated at specialized facilities followed by long periods of ambulatory care Consecutive Number of treatment initiation sites; number of patients enrolled to treatment; treatment outcomes (cured, completed, lost to follow up, died, failed) Evans et al, 2018 South Africa Retrospective cohort 2011 - 2014 594/713 Early/limited access to Xpert MTB/RIF (i.e 35% decentralization of Xpert MTB/RIF) Expanded/full access to Xpert MTB/RIF (i.e >90% access to Xpert MTB/RIF) Consecutive Proportion of patients initiated on treatment; time to treatment initiation; treatment outcomes (cured, completed, failure, lost to follow up, death) Mollel et al, 2019 Tanzania Retrospective cohort 2009 - 2013 14/90 Diagnosis by Xpert MTB/RIF and treatment at a single specialized hospital Diagnosis by Xpert MTB/RIF at 10 peripheral health facilities Consecutive Number of patients initiated to treatment; time to treatment initiation; treatment outcomes (cured, completed, lost to follow up, failure, death) Ramma et al, 2015 South Africa Cost analysis 2013 82/52 Hospital-based care Ambulatory-based care Concurrent Patient costs Alemayehu et al, 2020 Ethiopia Cost-effectiveness analysis NR 128/115 Hospital-based care Ambulatory-based care NR Health system costs Loveday et al, 2018 South Africa Cost-effectiveness analysis 2008 - 2010 582/70 Treatment at a specialized central hospital Treatment at community-based clinic or by mobile healthcare provider team Concurrent Health system costs; treatment outcomes (cured, completed, success, died, failed, defaulted, transferred out) Bada et al, 2019 Nigeria Cost analysis 2013 - 2014 NR Hospital-based care Community-based DOT by trained provider Concurrent Health system costs Bada et al, 2020 Nigeria Cost analysis N/A N/A Hospitalization followed by outpatient visits for DOT Ambulatory-mode of care through home-based DOT or clinic-based DOT N/A Health system costs NR – Not reported N/A – Not applicable Access to MDR-TB services Utilization of MDR-TB diagnostic services Two studies which assessed the effect of decentralizing MDR-TB diagnostic services on their utilization, noted increases in the number of samples tested when diagnostic services were decentralized. 40,41,43 The Kenyan study conducted by Sharma et al between 2012 and 2013, found that a higher number of patients (n = 238) registered in hospitals referring to the regional laboratory underwent Drug Susceptibility Testing [3] (DST) compared to those registered in hospitals referring to the central laboratory (n = 88) ( Table 3 ). 43 Similarly, an increase in number of patients tested for MDR-TB was noted by Molla and colleagues between 2012 and 2015 in Ethiopia. 40 At baseline, in 2012, only two centres which could perform culture for MDR-TB existed and no GeneXpert machines (machines used to diagnose TB and detect drug-resistance) were available. 40 At the end of the program, 2015, five laboratories were equipped for liquid culture and DST and 49 GeneXpert centres existed. 40 This led to an increase in the number of samples tested per year, from 662 in 2012 to 14,361 in 2015 ( Table 3 ). 40 Utilization of MDR-TB treatment services Two out of three studies that examined the effect of decentralizing MDR-TB treatment services reported an increase in the number of enrolled patients after decentralization. 40,42 Kasozi and colleagues noted that only three sites were able to initiate MDR-TB treatment in 2012, prior to expanding treatment initiating facilities and allowing outpatient DOT. 42 At the end of the intervention, in 2017, treatment could be initiated at 15 sites. 42 This increased the number of patients enrolled into care from 41 at baseline (2012) to over 200 patients every year, amounting to a cumulative total of 1311 patients enrolled into care in 2017 ( Table 3 ). 42 In the Ethiopian study, 56 patients were enrolled for treatment in the only available MDR-TB treatment initiating facility at baseline (2012). 40 At the end of the program in 2015, a cumulative total of 790 patients were enrolled for MDR-TB treatment from 23 established facilities with, 155, 254 and 325 patients enrolled in the years 2013, 2014 and 2015 respectively. 40 A study conducted in Tanzania by Mollel et al , 2019, reported an increase in the number of patients enrolled into care from 14 to 90 when diagnostic services (Xpert MTB/RIF machines) were decentralized to 10 peripheral facilities in 2013 (Table 3). 41 Prior to decentralization, patient enrolment into care relied on DST results from the Central Tuberculosis Reference Laboratory. 41 Table 3: Table showing MDR-TB service utilization in centralized and decentralized models Study Study design Country Utilization of services Centralized (n) Decentralized (n) Utilization of diagnostic services (number of samples tested for MDR-TB) Sharma et al, 2015 Cross-sectional Kenya 88 238 Molla et al, 2017 Interrupted time series Ethiopia 662 14361 Utilization of treatment services (number of patients enrolled into MDR-TB care) Kasozi et al, 2020 Interrupted time series Uganda 41 1311 Mollel et al, 2019 Retrospective cohort Tanzania 14 90 Molla et al, 2017 Interrupted time series Ethiopia 56 790 n = number of samples tested for MDR-TB or number of patients enrolled into MDR-TB care Cost of MDR-TB care Studies suggested that lower treatment costs were related to decentralized services than centralized services. Three studies, from Ethiopia, Nigeria and South Africa, noted that treatment costs per patient was lower by 24.9%, 48.8% and 54.6% in the three countries, respectively, when ambulatory care was compared to hospital-based care ( Table 4 ). 34,37,39 The same was noted by two studies comparing treatment costs between hospital-based and community-based approaches. These studies noted that 77.7% and 49.1% less cost was incurred when treatment was offered using community-based models than using centralized models in South Africa and Nigeria, respectively ( Table 4 ). 35,38 The study from Ethiopia also compared the cost-effectiveness between hospital-based and ambulatory-based models of care. Alemayehu and colleagues, 2020, reported that the average cost per DALY averted was $671 for an ambulatory treatment approach while for a hospital-based approach it was $1,417 per DALY averted. 39 Table 4: Table showing costs for MDR-TB care in decentralized and centralized models Study Study design Country Centralized care Decentralized care Difference in cost per-patient (centralized vs decentralized care) * Description Cost (US$/patient) Description Cost (US$/patient) Ramma et al, 2015 Cost analysis from a patient's perspective South Africa Hospital-based care 269.2 Ambulatory-based care 122.1 -54.6% Alemayehu et al, 2020 Cost-effectiveness analysis from a provider's perspective Ethiopia Hospital-based care (HIV positive) 1922 Ambulatory-based care (HIV positive) 1443 -24.9% Hospital-based care (HIV negative) 1798 Ambulatory-based care (HIV negative) 1391 -22.6% Loveday et al, 2018 Cost-effectiveness analysis from a provider's perspective South Africa Treatment at a specialized central hospital 30185 Treatment at community-based clinic 6739 -77.7% Treatment at community-by mobile healthcare provider team 9394 -68.9% Bada et al, 2019 Cost analysis from a provider's perspective Nigeria Hospital-based care 18528 Community-based DOT by trained provider 9424 -49.1% Bada et al, 2020 Cost analysis from a provider's perspective Nigeria 8month hospitalization followed by 12 months of outpatient care 14781 A fully ambulatory model for 20 months 7572 -48.8% 4months hospitalization followed by 5 - 8 months of outpatient care 7705 A fully ambulatory model for 9 - 12 months 4334 -43.8% * - Difference = (Cost in decentralized – Cost in centralized model) / Cost in centralized model MDR-TB treatment outcomes Table 5 summarizes prevalence estimates for each treatment outcome for the centralized and decentralized models. Treatment success Two prospective cohort studies conducted by Loveday and colleagues in KwaZulu-Natal (KZN), South Africa in 2015 and 2018 reported higher treatment success estimates for the decentralized model of care than the centralized model. 11,35 In these studies, treatment success for the centralized model were estimated to be 54% and 54.1%, respectively. 11,35 Treatment success for the decentralized model were estimated to be 58% in 2015 and 64.3% in 2018. 11,35 Two studies, however, found reduced treatment success estimates with decentralized models compared to a centralized model. Evans et al , 2018, noted 32.9% of those treated by a centralized model were successfully treated while 29.6% of those treated by a decentralized model were successfully treated. 33 Kasozi et al , 2020, reported that 78% of patients were successfully treated at baseline (2012) while the overall treatment success estimate reduced to 72.6% during the decentralization program in 2015. 42 However, proportions from the Ugandan study are from a population of 41 patients at baseline and 649 patients enrolled to treatment during decentralization (2013 – 2015). 42 In the three years of decentralization, the program consistently noted high success rates (73.9%, 2013; 74.1%, 2014; and 70.1%, 2015) even with increasing population sizes. 42 Lost to follow-up (LTFU) Three studies by Loveday et al , in 2012, 2015 and 2018 reported reduced estimates of LTFU for decentralized treatment approaches compared to a centralized approach. 11,35,36 In two of the studies, LTFU estimates of patients treated in decentralized facilities were nearly half of those treated in a centralized hospital (14.5% vs 28.3%, 2015 and 12.9% vs 24.9%, 2018). 11,35 In the 2012 study, 18.9% of patients treated in decentralized facilities were lost to follow-up while those treated in a centralized hospital and were lost to follow-up was 30.2%. 36 Kasozi et al and Evans et al , reported similar estimates of LTFU for the two approaches. Kasozi et al , reported that 9.8% and 10.9% of patients were LTFU before decentralization and after three years of decentralizing MDR-TB services, respectively. 42 Evans et al , reported that 55.3% of patients utilizing the centralized model were LTFU while 55.9% of patients under the decentralized model were LTFU. 33 Death Loveday et al , in 2012, reported that 6.8% of patients under centralized care died while 16% of patients under decentralized care died. 36 Kasozi et al , 2020, noted that 5% of patients receiving treatment under the centralized model died while 15% of those receiving treatment using the decentralized model died. 42 While Loveday et al, 2015 and Evans et al, 2020 also reported higher death estimates among patients treated using a decentralized model, these differences were not shown to be statistically significant. 11,33 According to Loveday et al in 2015, 14% of patients using the centralized model died while 18% of those using the decentralized model died. 11 Also, 12% of patients receiving centralized care died while 14% of those receiving decentralized care died, as reported in 2020 by Evans et al. 33 Being HIV positive with MDR-TB and not on antiretroviral therapy (ART) was associated with these high death estimates. 11,33 Treatment failure Similar treatment failure estimates between the two treatment models were reported by Evans et al and Kasozi et al. Both studies reported no treatment failure before decentralization and 0.3% and 1.1% failure estimates after decentralization, respectively. 33,42 Three studies by Loveday et al reported increased treatment failure estimates for the decentralized model compared to centralized model. In 2012, the authors noted no patient (0.0%) failing treatment in the centralized group while 15 (3.6%) patients failed treatment in the decentralized group. 36 Also, in 2015, the authors noted that 3.6% of patients failed treatment in the centralized group while 6.7% of patients in the decentralized group failed treatment. 11 Although, increased estimates of failing treatment were also reported in 2018 by Loveday et al (3.3% in centralized group vs 7.1% in decentralized group), the sample size of the two groups differed significantly (582 vs 70 respectively). 35 Table 5. Table showing prevalence estimates of treatment outcomes for patients treated using decentralized and centralized approaches Study Centralized care Decentralized care Total patients Number of patients (%) Total patients Number of patients (%) Treatment success Lost to follow up Death Treatment failure Others Treatment success Lost to follow up Death Treatment failure Others Loveday et al, 2015 813 439 (54) 230 (28.3) 113 (13.9) 29 (3.6) 2 (0.2) a 736 427 (58.0) 107 (14.5) 133 (18.1) 49 (6.7) 20 (2.7) a Loveday et al, 2012 441 ONA 133 (30.2) 30 (6.8) 0 (0.0) 278 (63.0) b 419 ONA 79 (18.9) 67 (16) 15 (3.6) 258 (61.6) b Kasozi et al, 2020* 41 32 (78.0) 4 (9.8) 2 (4.9) 0 (0.0) 3 (7.3) c 649 471 (72.6) 71 (10.9) 100 (15.4) 7 (1.1) 0 (0.0) c Evans et al, 2018 161 53 (32.9) 89 (55.3) 19 (11.8) 0 (0.0) 365 108 (29.6) 204 (55.9) 52 (14.2) 1 (0.3) Loveday et al, 2018 582 315 (54.1) 145 (24.9) 101 (17.4) 19 (3.3) 2 (0.3) a 70 45 (64.3) 9 (12.9) 8 (11.4) 5 (7.1) 3 (4.3) a a – Transferred out b – Still on treatment c – Not evaluated * - Outcomes up until 2015 only, study ended in 2017 ONA - Outcome Not Assessed [3] Drug-susceptibility testing refers to in-vitro testing using either phenotypic methods to determine susceptibility or molecular techniques to detect resistance-conferring mutations to a medicine. 7 Discussion This review aimed to examine the effect of decentralizing MDR-TB services on the accessibility of services and patient treatment outcomes in sub-Saharan Africa. Findings from this study suggest that decentralizing MDR-TB care in SSA has improved access to services through increased utilization of MDR-TB services and reduction of MDR-TB treatment cost. Findings also suggest that decentralizing MDR-TB services has contributed to increased successful treatment and retention of patients to care. Access to MDR-TB services Utilization of diagnostic and treatment services All studies included in this review reported higher numbers of patients accessing and utilizing decentralized MDR-TB diagnostic and treatment services than centralized services. 40–43 Similar findings are reported by studies conducted in other low- and middle-income countries (LMICs) such as Peru, Bangladesh and Myanmar. 44–46 This enriches the evidence of the vital importance of decentralized approaches in ensuring MDR-TB patient’s access to services in resource limited settings such as those of SSA. Widespread availability of MDR-TB diagnostic and treatment services after decentralization is reason for the higher numbers accessing and utilizing services. 40,42,43 Cost of MDR-TB treatment All cost studies included in this review suggested that MDR-TB care using decentralized approaches is less costly than using centralized approaches. 34,35,37–39 Alemayehu et al , 2020, the only study which reported cost-effectiveness using economic models, also suggested that decentralized care is more cost-effective than centralized care. 39 These findings are consistent with other systematic reviews conducted by Fitzpatrick C. and Floyd K, and Ho et al. 9,47 Findings from the current review, therefore, imply that decentralization of MDR-TB services can be operationalized at affordable costs in the sub-Saharan setting. However, most cost-analyses included in this review did not capture MDR-TB patient’s costs. 35,37–39 The only study to do so noted that, even patients using ambulatory approaches can face catastrophic costs and calls for socio-economic support systems to be in place. 34 While the major cost driver for centralized care was hospitalization, for decentralized care was outpatient consultation and supervision. 34,38 Using decentralized care, however, has an added benefit of preserving patient’s social support structure and earlier treatment initiation. 38 MDR-TB treatment outcomes Treatment success Success rates in some studies were found to be higher for decentralized model of care than for the centralized model. 11,35,40 A critical step in ensuring this achievement was noted to be early detection and management through strengthening technical and infrastructure capacity. 40 Similar results were reported by previous studies assessing treatment outcomes for decentralized models. 48,49 While support from external organizations (e.g. international donors) contributed to the success rate in these studies by offering comprehensive treatment packages, some studies included in this review reported no external support for the decentralization program. 11,48,49 This implies that decentralization of MDR-TB services can successfully be implemented in resource limited settings such as those of SSA to achieve MDR-TB treatment success. In contrast, Kasozi and colleagues reported, in their interrupted time series, a reduction in overall treatment success estimates during a decentralization program. 42 Despite this reduction, the program was able to maintain high levels of treatment success amidst the large expansion in patient volumes. 42 This suggests that governments within sub-Saharan Africa can maintain high treatment success rates even with increased patient numbers. This can be achieved by implementing continuous quality improvement strategies such as peer-to-peer mentorships and holding learning sessions as applied in Uganda. 42 Lost to follow up Decentralized MDR-TB care was related to lower estimates of LTFU in most studies conducted in South Africa. 11,35,36 Contrastingly, a study in Uganda reported similar estimates of LTFU between the two approaches. 42 This difference could be attributed to low capacity and lack of experience in MDR-TB management of selected sites during decentralization in Uganda. 42 Similar LTFU estimates between the two treatment approaches were also reported by Evans et al in South Africa. 33 In agreement with these findings are systematic reviews and meta-analyses conducted by Bassili et al and Ho et al . 9,22 Therefore, decentralization of MDR-TB in SSA, has potential to reduce estimates of LTFU when treatment sites are adequately capacitated. Death While most studies in this review reported higher death estimates among patients in decentralized sites than in centralized site, 11,36,42 only one study reported a statistically significant difference. 36 The difference noted in this study is reported to have been probably due to missing data in registers from which data was extracted at centralized sites. 36 This may have led to underestimation of death estimates at the centralized site. Despite the observation in the Ugandan study, there was a large difference between the sample sizes of the two arms (centralized arm; 41 patients vs decentralized arm; 649 patients), from which estimates were calculated. 42 Consequently, the noted difference in death estimates seems to be insignificant, as with findings from some studies included in this review and other systematic reviews. 9,11,22,33 Treatment failure Consistent with findings from other studies, estimates of MDR-TB treatment failure for decentralized and centralized care were found to be similar in some studies included in this review. 9,33,42,50 However, other studies included in this review reported higher estimates of treatment failure in decentralized settings than in centralized settings. 11,36 Even with these observed differences, reported estimates did not exceed the global treatment failure estimate. 2 Study strengths and limitations Strengths of this review include, a comprehensive literature search from scientific databases and using strict eligibility criteria to limit the review to studies with patients receiving a decentralized and centralized care. This allowed studies to be selected without bias and comparisons be made from same population groups in similar settings. This review also had several limitations. Grey literature was not included in the review as it focused only on literature published in scientific journals. This restricted synthesis of evidence from reports documented by governments and TB fighting NGOs within the region. Literature search was limited to studies published in English, preventing identification of studies published in French, Portuguese and Arabic which are official languages used by several SSA countries. Therefore, findings from these countries were not examined. Despite searching for literature using country names of sub-Saharan Africa, numerous countries within the region had no studies published on the subject. This limited the analysis to some regions within SSA and prompts cautious use of findings from this review. While none of the included studies received a weak rating on the EPHPP tool, most studies were of moderate quality because they were observational studies. This limits generalizability of findings from this systematic review and underpins the importance of further research on the effects of decentralization of MDR-TB care in various settings within sub-Saharan Africa. Conclusion In conclusion, included studies have suggested that decentralizing MDR-TB services in SSA has increased access to MDR-TB services. More patients have been tested, diagnosed and enrolled into MDR-TB care in the region. Managing MDR-TB using decentralized models is also suggested to be less costly and more cost-effective than using centralized models. This is pertinent to SSA due to resource-constraints in many countries within the region. Also, through decentralizing MDR-TB services, countries in SSA are suggested to achieve and maintain high treatment success rates as well as retain more patients into care. Sub-Saharan African countries are, therefore, recommended to manage MDR-TB using more decentralized approaches than centralized approaches. Decentralized facilities should be well capacitated to ensure quality care is provided to MDR-TB patients. Efficient data recording systems should also be established at decentralized facilities as well as central facilities. This will enable effective monitoring and evaluation of various components of MDR-TB management such as patient treatment outcomes. More robust study designs such as randomized studies, e.g. stepped-wedge cluster randomized studies, are recommended as well as meta-analyses to estimate pooled estimates of treatment outcomes for the two treatment approaches in sub-Saharan Africa. Abbreviations ART Antiretroviral Therapy DALY Disability Adjusted Life Years DOT Direct Observed Therapy DR-TB Drug-resistant tuberculosis DST Drug susceptibility testing KZN KwaZulu Natal LMIC Low- and Middle-Income Countries LTFU Lost to follow up MDR Multidrug-resistance MDR-TB Multidrug-resistant tuberculosis NGO Non-Governmental Organization RR-TB Rifampicin-resistant tuberculosis SSA Sub-Saharan Africa WHO World Health Organization XDR-TB Extensive drug-resistant tuberculosis Declarations Ethics approval and consent to participate Approval to conduct this study was granted by the University of Witwatersrand ethics committee (Medical), reference number, W–CBP–210219-01. A copy of the waiver from ethics certificate is attached as additional file. Consent for publication Not applicable Availability of data and materials All data generated or analysed during this study are included in this published article [and its supplementary information files]. Competing interests The authors declare that they have no competing interests. Funding The research project was supported by a postgraduate training Scholarship from the TDR, the UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases - hosted at the World Health Organization in Geneva, Switzerland. TDR grant number: B40299. First author ORCID ID: 0000-0001-6298-3549 TDR played no role in the study. Author’s contributions MA designed the study, searched for published studies in databases, selected the studies for inclusion, assessed the quality of included studies, extracted, analysed and interpreted the data from studies, and was a major contributor in writing the manuscript. YL participated in study selection, quality assessment of included studies, re-checking information extracted from studies, reading and reviewing the manuscript. SM participated in the design of the study as well as reading and reviewing the manuscript. LI participated in the design of the study as well as reading and reviewing the manuscript. Acknowledgements The authors thank Godwin Kalu for proofreading the manuscript. References 1. Barberis I, Bragazzi NL, Galluzzo L, Martini M. The history of tuberculosis: From the first historical records to the isolation of Koch’s bacillus. J Prev Med Hyg. 2017;58(1):E9–12. 2. WHO. Global tuberculosis report 2020. Geneva: World Health Organization; 2020. [Internet]. 2020. Available from: http://apps.who.int/iris. 3. Anon. Nosocomial Transmission of Multidrug-Resistat Tuberculosis in Florida and New York, 1988 - 1991. Mmwr. 1991;40(34):585–91. 4. Rullán J V., Herrera D, Cano R, Moreno V, Godoy P, Peiró EF, et al. Nosocomial Transmission of Multidrug-Resistant Mycobacterium tuberculosis in Spain. Emerg Infect Dis. 1996;2(2):125–9. 5. Frieden TR, Sterling T, Pablos-Mendez A, Kilburn JO, Cauthen GM, Dooley SW. The Emergence of Drug-resistant Tuberculosis in New York City. 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PLoS One [Internet]. 2020;15(12 December):1–14. Available from: http://dx.doi.org/10.1371/journal.pone.0241065 38. Bada FO, Okpokoro E, Blok N, Meribole E, Dutt S, Dakum P, et al. Cost of three models of care for drug-resistant tuberculosis patients in Nigeria. BMC Infect Dis. 2019 Jan;19(1):41. 39. Alemayehu S, Yigezu A, Hailemariam D, Hailu A. Cost-effectiveness of treating multidrug-resistant tuberculosis in treatment initiative centers and treatment follow-up centers in Ethiopia. PLoS One. 2020;15(7):e0235820. 40. Molla Y, Jerene D, Jemal I, Nigussie G, Kebede T, Kassie Y, et al. The experience of scaling up a decentralized, ambulatory model of care for management of multidrug-resistant tuberculosis in two regions of Ethiopia. J Clin Tuberc Other Mycobact Dis [Internet]. 2017;7:28–33. Available from: http://dx.doi.org/10.1016/j.jctube.2017.03.001 41. Mollel E, Lekule I, Lynen L, Decroo T. Effect of reliance on Xpert MTB/RIF on time to treatment and multidrug-resistant tuberculosis treatment outcomes in Tanzania: a retrospective cohort study. Int Health. 2019 Nov;11(6):520–7. 42. Kasozi S, Kirirabwa NS, Kimuli D, Luwaga H, Kizito E, Turyahabwe S, et al. Addressing the drug-resistant tuberculosis challenge through implementing a mixed model of care in Uganda. PLoS One. 2020;15(12):e0244451. 43. Sharma A, Musau S, Heilig CM, Okumu AO, Opiyo EO, Basiye FL, et al. Assessing the effect of decentralisation of laboratory diagnosis for drug-resistant tuberculosis in Kenya. Int J Tuberc Lung Dis. 2015 Feb;19(11):1348–53. 44. Daru P, Matji R, Almossawi J, Chakraborty K. Decentralized, Community-Based Treatment for Drug- Resistant Tuberculosis: Bangladesh Program Experience. Glob Heal Sci Pract [Internet]. 2018;6(3):594–603. Available from: https://doi.org/10.9745/GHSP-D-17-00345 45. Thu MK, Kumar AMV, Soe KT, Saw S, Thein S, Mynit Z, et al. High treatment success rate among multidrug-resistant tuberculosis patients in Myanmar, 2012-2014: A retrospective cohort study. Trans R Soc Trop Med Hyg. 2017;111(9):410–7. 46. Shin SS, Yagui M, Ascencios L, Yale G, Suarez C, Quispe N, et al. Scale-up of Multidrug-Resistant Tuberculosis Laboratory Services, Peru. Emerg Infect Dis. 2008;14(5):701–8. 47. Fitzpatrick C, Floyd K. A Systematic Review of the Cost and Cost Effectiveness of Treatment for Multidrug-Resistant Tuberculosis. Pharmacoeconomics [Internet]. 2012;30(1):63–80. Available from: https://doi.org/10.2165/11595340-000000000-00000 48. Morris L, Hiasihri S, Chan G, Honjepari A, Tugo O, Taune M, et al. The emergency response to multidrug-resistant tuberculosis in Daru, Western Province, Papua New Guinea, 2014-2017. Public Heal Action [Internet]. 2019 Sep 21;9(Suppl 1):S4–11. Available from: http://dx.doi.org/10.5588/pha.18.0074 49. Mitnick C, Bayona J, Palacios E, Shin S, Furin J, Alcántara F, et al. Community-Based Therapy for Multidrug-Resistant Tuberculosis in Lima, Peru. N Engl J Med. 2003;348(2):119–28. 50. Sam S, Shapiro AE, Sok T, Khann S, So R, Khem S, et al. Initiation, scale-up and outcomes of the Cambodian National MDR-TB programme 2006-2016: hospital and community-based treatment through an NGO-NTP partnership. BMJ open Respir Res. 2018;5(1):e000256. Additional Declarations No competing interests reported. Supplementary Files AdditionalFile1EPHPPTool.docx File name: Additional file 1 (EPHPP Tool) File format: Word document (.doc) Title: The Effective Public Health Practice Project tool Description: Quality assessment tool for observational studies AdditionalFile2CHEERSChecklist.docx File name: Additional file 2 (CHEERS Checklist) File format: Word document (.doc) Title: The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist Description: Quality assessment tool for cost analysis studies. AdditionalFile3EthicsWaiverCertificate.pdf File name: Additional file 3 (Ethics Waiver Certificate) File format: Portable document format (.pdf) Title: Ethics Waiver Certificate Description: A certificate waiving the requirement of ethics clearance from the Human Research Ethics Committee (HREC) of the University of the Witwatersrand. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-2077078","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":138728212,"identity":"aeb6408d-25ab-4ab5-8679-8ad15189668f","order_by":0,"name":"Meckie 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Witwatersrand.\u003c/p\u003e","description":"","filename":"AdditionalFile3EthicsWaiverCertificate.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2077078/v1/a804be008b0020f731287868.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"The Effect of Decentralized Services on Multidrug-Resistant Tuberculosis Care in Sub- Saharan Africa: A Systematic Review","fulltext":[{"header":"Background","content":"\u003cp\u003eTuberculosis (TB), an airborne disease caused by \u003cem\u003eMycobacterium tuberculosis\u003c/em\u003e, has been a global health concern for many decades.\u003csup\u003e1\u003c/sup\u003e The World Health Organization (WHO)\u0026rsquo;s 2020 Global report on TB estimated 10 million new TB cases, and 1.2 million deaths.\u003csup\u003e2\u003c/sup\u003e Since the early 1990s, the emergence of multidrug-resistant strains of TB (MDR-TB)\u003ca href=\"#_ftn1\" name=\"_ftnref1\" title=\"\"\u003e[1]\u003c/a\u003e, has challenged TB control programmes worldwide.\u003csup\u003e1,3\u0026ndash;6\u003c/sup\u003e The estimated incidence of MDR-TB was reported to be 465,000 cases, which is a combined total of 3.3% of new TB cases and 18% of previously treated TB cases.\u003csup\u003e2\u003c/sup\u003e The African region ranked third in the incidence of MDR-TB in 2019 globally, with 17% of all reported cases.\u003csup\u003e2\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eProgrammatic management of MDR-TB has transitioned from a centralized to a decentralized care model. A centralized model is one whereby, MDR-TB patients are treated as inpatients in designated, specialized DR-TB treatment facilities.\u003csup\u003e7\u003c/sup\u003e In this model, patients are usually treated by specialized provider(s) throughout the intensive phase of treatment or until negative diagnostic results (through culture or smear conversion).\u003csup\u003e7\u003c/sup\u003e While this approach allows easier monitoring of patients\u0026rsquo; adherence to medication and adverse events, it is not without limitations.\u003csup\u003e8,9\u003c/sup\u003e Among the limitations of this approach are; delays in treatment initiation due to insufficient bed capacities, limited human resources to deliver care and increased socioeconomic costs associated with hospitalization.\u003csup\u003e10\u003c/sup\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003eAlso, centralized facilities are sometimes located far from patients\u0026rsquo; homes necessitating patients to travel long distances to access services.\u003csup\u003e11\u003c/sup\u003e The situation is more marked in resource limited settings such as those of SSA.\u003csup\u003e9,12\u003c/sup\u003e As a result, in 2011, the WHO recommended decentralized care for MDR-TB.\u003csup\u003e13\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eContrary to centralized care, decentralized MDR-TB care, is defined as management (treatment and care) of MDR-TB provided at the community where the patient resides.\u003csup\u003e9\u003c/sup\u003e This approach mainly incorporates ambulatory modes of care which can be defined as care provided on an outpatient basis.\u003csup\u003e7\u003c/sup\u003e Ambulatory care can be clinic-based where patients attend a peripheral clinic, or community-based which utilizes local health care workers (HCWs), former patients, co-workers, neighbours or family members to directly observe treatment without frequent visits to a health care facility.\u003csup\u003e12,13\u003c/sup\u003e Community-based care is also referred to as home-based mode of care.\u003csup\u003e13\u003c/sup\u003e Decentralized care for MDR-TB has been reported to improve access to MDR-TB diagnostic and treatment services.\u003csup\u003e10\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eService affordability is the ability to pay for services without facing financial hardship.\u003csup\u003e14\u003c/sup\u003e It is an integral component to achieving universal access to health services.\u003csup\u003e14\u003c/sup\u003e It accounts for direct costs (e.g. price of health services), indirect costs (e.g. transportation to health facilities) and opportunity costs (e.g. taking time off work) of health services, including MDR-TB services.\u003csup\u003e14\u003c/sup\u003e\u0026nbsp; To our knowledge no review has \u0026nbsp;examined these costs as experienced by MDR-TB service providers (health system) and recipients of MDR-TB services (patients) in sub-Saharan Africa.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe present review, focuses on access to services in terms of affordability and utilization of services as these areas fall short of the target set in the End TB Strategy and at the United Nations (UN) high-level meeting on TB in 2018, respectively.\u003csup\u003e2,19\u003c/sup\u003e The End TB Strategy, adopted in 2014, targeted that no household affected by TB faces catastrophic costs\u003ca href=\"#_ftn2\" name=\"_ftnref2\" title=\"\"\u003e[2]\u003c/a\u003e by 2020.\u003csup\u003e2,19\u003c/sup\u003e However, pooled estimates published in 2022 show that more than 78% of MDR-TB affected households still face catastrophic costs.\u003csup\u003e20\u003c/sup\u003e In the UN meeting, a global target of treating 1.5 million people by 2022 was set.\u003csup\u003e2\u003c/sup\u003e By 2019, only 333,000 people (22% of target) had received treatment for MDR-TB globally.\u003csup\u003e2\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn previous systematic reviews which compared MDR-TB treatment outcomes between centralized and decentralized approaches, only a handful of SSA countries were represented and none focused specifically on SSA.\u003csup\u003e9,10,22\u003c/sup\u003e To our knowledge, there has also been no systematic evaluation of the effect of decentralization on the accessibility of MDR-TB services since its recommendation. This review, therefore, aims to examine the effect of decentralizing MDR-TB care on access (in terms of utilization and cost) to services and patient treatment outcomes in sub-Saharan Africa. Findings from this study will elucidate the effect of decentralized approaches in MDR-TB care within the SSA context. Consequently, this could inform decision making processes to the adoption of decentralized approaches across the SSA region.\u003c/p\u003e\n\u003cdiv id=\"ftn1\"\u003e\n \u003cp\u003e\u003ca href=\"#_ftnref1\" name=\"_ftn1\" title=\"\"\u003e[1]\u003c/a\u003e Multidrug-resistant tuberculosis (MDR-TB) is tuberculosis caused by \u003cem\u003eMycobacterium tuberculosis\u003c/em\u003e strains that exhibit resistance to both rifampicin and isoniazid.\u003csup\u003e7\u003c/sup\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"ftn2\"\u003e\n \u003cp\u003e\u003ca href=\"#_ftnref2\" name=\"_ftn2\" title=\"\"\u003e[2]\u003c/a\u003e Catastrophic costs are defined as total costs equivalent to \u0026gt;20% of annual household income.\u003csup\u003e2\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/div\u003e"},{"header":"methods","content":"\u003ch2\u003e\u003cstrong\u003eSetting\u003c/strong\u003e\u003cstrong\u003es\u0026nbsp;\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003eSub-Saharan African region spans from the southern border of the Saharan Desert to the southern tip of the African continent. It is home to over 1.1 billion people, 42.3% of which live in extreme poverty (% population below $1.90 a day).\u003csup\u003e23\u0026ndash;25\u003c/sup\u003e Thus, poverty, together with weak health systems characterised by inadequate diagnostic services, medical supplies and human resource capacities pose hindrances to the deployment and sustainability of MDR-TB interventions.\u003csup\u003e26\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFurther, nearly half (47%) of the urban residents in sub-Saharan Africa live in unimproved houses - houses with poor sanitation, poor water supply, uncompleted buildings and/or crowded houses with more than three people living in a single room.\u003csup\u003e27,28\u003c/sup\u003e These conditions have been shown to influence MDR-TB transmission and consequently increase the disease burden.\u003csup\u003e29\u003c/sup\u003e\u003c/p\u003e\n\u003ch2\u003eStudy design\u003c/h2\u003e\n\u003cp\u003eThe present systematic review was conducted and reported following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The PRISMA is a 27-item guideline developed to guide the reporting of systematic reviews and meta-analyses.\u003csup\u003e30\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003e\u003cstrong\u003eEligibility criteria\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003eEligibility criteria for studies included in the review are presented in Table 1 below.\u003c/p\u003e\n\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:12px;font-family:\"Times New Roman\",serif;color:#44546A;font-style:italic;line-height:200%;'\u003e\u003cstrong\u003e\u003cspan style=\"font-size:16px;line-height:200%;color:black;font-style:normal;\"\u003eTable\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan style=\"font-size:16px;line-height:200%;color:black;font-style:normal;\"\u003e1\u003c/span\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan style=\"font-size:16px;line-height:200%;color:black;font-style:normal;\"\u003e: Table showing eligibility criteria for study selection\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003ctable style=\"width:531.6pt;border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 106.35pt;border: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003e\u003cstrong\u003e\u003cspan style=\"line-height:150%;\"\u003eCriteria\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 425.25pt;border-top: 1pt solid windowtext;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-image: initial;border-left: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003e\u003cstrong\u003e\u003cspan style=\"line-height:150%;\"\u003eDescription\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 106.35pt;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-left: 1pt solid windowtext;border-image: initial;border-top: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003e\u003cspan style=\"line-height:150%;\"\u003eLocation\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 425.25pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003e\u003cspan style=\"line-height:150%;\"\u003eThe study had to have been conducted in a country or in countries that are within the sub-Saharan African region.\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003e\u003cspan style=\"line-height:150%;\"\u003eAll studies conducted in countries outside SSA, including northern African countries (Egypt, Libya, Algeria, Morocco, Tunisia and Western Sahara) were excluded from the review. \u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 106.35pt;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-left: 1pt solid windowtext;border-image: initial;border-top: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003e\u003cspan style=\"line-height:150%;\"\u003eStudy design\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 425.25pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003e\u003cspan style=\"line-height:150%;\"\u003eInterrupted time series, observational studies (prospective and retrospective cohort studies, case control studies and cross-sectional studies) and cost evaluation studies were included in the review. Studies with a qualitative\u0026nbsp;\u003c/span\u003e\u003cspan style=\"font-size:15px;line-height:150%;\"\u003eand experimental\u0026nbsp;\u003c/span\u003e\u003cspan style=\"line-height:150%;\"\u003edesign\u0026nbsp;\u003c/span\u003e\u003cspan style=\"font-size:15px;line-height:150%;\"\u003e(e.g RCTs)\u0026nbsp;\u003c/span\u003e\u003cspan style=\"line-height:150%;\"\u003ewere excluded from the review. \u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 106.35pt;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-left: 1pt solid windowtext;border-image: initial;border-top: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003e\u003cspan style=\"line-height:150%;\"\u003eComparison groups\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 425.25pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003e\u003cspan style=\"line-height:150%;\"\u003eThe study should be comparing patients receiving \u003cstrong\u003edecentralized\u003c/strong\u003e (ambulatory or community-based) mode of care and those receiving a \u003cstrong\u003ecentralized\u003c/strong\u003e mode of care for MDR-TB treatment.\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003e\u003cem\u003e\u003cspan style=\"line-height:150%;\"\u003eDecentralized MDR-TB care was considered to be one which is purely provided on an outpatient basis, from treatment initiation to completion. Also, for diagnostic services (e.g. laboratory services), decentralized care was one where diagnosis is done at facilities other than the central laboratory.\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003e\u003cem\u003e\u003cspan style=\"line-height:150%;\"\u003eCentralized MDR-TB care was considered to be care which is provided on an in-patient basis at designated specialized facilities by specialized providers.\u0026nbsp;\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 106.35pt;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-left: 1pt solid windowtext;border-image: initial;border-top: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003e\u003cspan style=\"line-height:150%;\"\u003eOutcomes\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 425.25pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003e\u003cspan style=\"line-height:150%;\"\u003eThe study should have reported at least one treatment outcome as per WHO standards, including, cure, completion, success, death, failure, default/lost to follow-up. Studies reporting the number of patients utilizing MDR-TB services, and/or cost of MDR-TB services were also included. All studies \u003cstrong\u003esolely\u003c/strong\u003e reporting treatment outcomes and/or cost for RR-TB, pre-XDR and XDR-TB, and not for MDR-TB, were excluded from the review.\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 106.35pt;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-left: 1pt solid windowtext;border-image: initial;border-top: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003e\u003cspan style=\"line-height:150%;\"\u003eData source\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 425.25pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003e\u003cspan style=\"line-height:150%;\"\u003eStudies published in peer reviewed journals.\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 106.35pt;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-left: 1pt solid windowtext;border-image: initial;border-top: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003e\u003cspan style=\"line-height:150%;\"\u003eYear of publication\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 425.25pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003e\u003cspan style=\"line-height:150%;\"\u003eBetween 2011 and 2021. This time period was selected because 2011 was the year when WHO recommended the decentralized approach and 2021 the year the study was conducted.\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 106.35pt;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-left: 1pt solid windowtext;border-image: initial;border-top: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003e\u003cspan style=\"line-height:150%;\"\u003eLanguage of published study\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 425.25pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003e\u003cspan style=\"line-height:150%;\"\u003eEnglish. No other languages were included as none of the reviewers were proficient in either French, Portuguese or Arabic. Also, there was limited time for translation services.\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003e\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003e\u003cstrong\u003eSearch strategy\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003eStudies conducted within sub-Saharan Africa focusing on decentralized and centralized treatment approaches for MDR-TB were sourced from five scientific databases: PubMed, Global health, Cochrane library, Scopus and Global Index Medicus. \u0026nbsp;The last search was conducted on January 28, 2021. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eKeywords that were used for the literature search are: \u0026ldquo;mdr-tb AND decentralization\u0026rdquo;, \u0026ldquo;mdr-tb AND community-based\u0026rdquo;, \u0026ldquo;mdr-tb AND ambulatory\u0026ldquo;, \u0026ldquo;mdr-tb AND sub-Saharan Africa\u0026rdquo;, \u0026ldquo;(mdr-tb AND decentralization) AND \u003cem\u003esub-Saharan country name\u003c/em\u003e\u0026rdquo;, \u0026ldquo;(mdr-tb AND community-based) AND \u003cem\u003esub-Saharan country name\u003c/em\u003e\u0026rdquo;, \u0026ldquo;(mdr-tb AND ambulatory) AND \u003cem\u003esub-Saharan country name\u003c/em\u003e\u0026rdquo;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eA manual search of literature was also conducted using the reference lists of studies that had been identified.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003e\u003cstrong\u003eStudy selection\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;and data extraction\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003eRetrieved studies from database and bibliographic searches were managed using Mendeley referencing manager software (version 1.19.8). The software (Mendeley) was used to screen and remove duplicates. Thereafter, titles and abstracts of retrieved studies were screened and those unrelated to the review topic were removed. The remaining studies were read full text and those not matching the eligibility criteria were excluded. Justification for study exclusion was documented (Figure 1). Two reviewers (MA and YL) worked independently during study selection and met to compare their inclusions. Differences on the inclusion/exclusion of studies between the two reviewers were resolved by consensus.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFigure 1. Flow diagram presenting the selection of studies on centralized and decentralized management of MDR-TB\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eKey information extracted from each study included; first author\u0026rsquo;s name, year of publication, study design, study setting, description of centralized and decentralized models of care and outcome(s) measured. Other information extracted from studies when available included; sample size of control and intervention groups, number of patients utilizing MDR-TB services, number of samples tested for MDR-TB, cost of MDR-TB services and prevalence estimates of MDR-TB treatment outcomes such as treatment success, loss to follow-up, death and treatment failure. Data were extracted by MA and re-checked YL.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003e\u003cstrong\u003eQuality assessment\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/h2\u003e\n\u003ch3\u003e\u003cem\u003eObservational studies and interrupted time series designs\u003c/em\u003e\u003c/h3\u003e\n\u003cp\u003eThe Effective Public Health Practice Project (EPHPP) tool was modified and used to assess the quality of observational studies (n=5) and interrupted time series (n=2). The EPHPP tool can be found as an additional file. The tool assesses six domains to establish the quality of a study.\u003csup\u003e31\u003c/sup\u003e However, one domain (blinding) was removed because it is a feature of experimental studies (eg RCTs) which were excluded from this study. Five domains, therefore, were used to establish the quality of these studies. The domains are; participant selection bias, design of study, confounding, data collection methods and withdrawals/dropouts.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eEach domain received a rating of being either weak (1 point), moderate (2 points) or strong (3 points). Scores from the domains were then added to derive a total score for each study. From the total score, an average score was calculated to get the global rating for a study. The minimum and maximum attainable global rating score per study was 1.00 and 3.00, respectively.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIndividual studies were then classified into either weak, moderate or strong categories depending on their global rating scores. Weak studies had a global rating score ranging between 1.00 \u0026ndash; 1.50, moderate studies scored between 1.51 \u0026ndash; 2.50 and strong studies obtained a score between 2.51 \u0026ndash; 3.00.\u003csup\u003e31\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe quality of six studies included in the review was classified as moderate and one study was classified as strong. No study was classified as weak.\u0026nbsp;\u003c/p\u003e\n\u003ch3\u003e\u003cem\u003eEconomic evaluation studies\u0026nbsp;\u003c/em\u003e\u003c/h3\u003e\n\u003cp\u003eThe Consolidated Health Economic Evaluation Reporting Standards (CHEERS) guideline was used for five studies that fall into this category. CHEERS is a 24-item checklist aimed at optimizing the reporting of health economic evaluations.\u003csup\u003e32\u003c/sup\u003e The checklist can be found as an additional file.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFor each item of the checklist, the page number and line to which the item is reported in each study were documented. Items which were not reported by studies and those which were not applicable to studies were also documented. Generally, the quality of reporting was good with three of the studies reporting all items that were applicable, one study reported all applicable items except two and the last study reported all but one applicable item.\u0026nbsp;\u003c/p\u003e"},{"header":"Results","content":"\u003ch2\u003e\u003cstrong\u003eStudy characteristics\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003eTwelve studies were eligible and included in this review (\u003ca href=\"#Study_selection_flow_diagram\"\u003eFigure 1\u003c/a\u003e). Five studies were from the southern African region (South Africa),\u003csup\u003e11,33\u0026ndash;36\u003c/sup\u003e two from the west African region (Nigeria)\u003csup\u003e37,38\u003c/sup\u003e and five from the east African region (Ethiopia (n=2),\u003csup\u003e39,40\u003c/sup\u003e Tanzania (n=1),\u003csup\u003e41\u003c/sup\u003e Uganda (n=1)\u003csup\u003e42\u003c/sup\u003e and Kenya (n=1)\u003csup\u003e43\u003c/sup\u003e). Four of the included studies were cohort studies,\u003csup\u003e11,33,36,41\u003c/sup\u003e 5 were cost analyses,\u003csup\u003e34,35,37\u0026ndash;39\u003c/sup\u003e 2 were interrupted time series\u003csup\u003e40,42\u003c/sup\u003e and one was a cross sectional study\u003csup\u003e43\u003c/sup\u003e (\u003ca href=\"#Study_characteristics\"\u003eTable 2\u003c/a\u003e).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFor the centralized model; 10 studies reported MDR-TB diagnosis and treatment at centralized hospitals, one study reported specimen diagnosis at a central laboratory and one study reported limited access (35% access) to diagnostic services during a scale-up project. For the decentralized model, 9 studies reported on MDR-TB treatment. The studies involved various treatment models such as ambulatory clinic-based model, home-based treatment and community-based treatment by mobile healthcare providers. One study reported specimen diagnosis at regional laboratories, one reported expanded access (\u0026gt;90% access) to diagnostic services during a scale-up project and one reported expansion of diagnostic services to peripheral facilities (Table 2).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eUtilization of MDR-TB services was reported by four studies.\u003csup\u003e40\u0026ndash;43\u003c/sup\u003e Two of these reported utilization of treatment services alone,\u003csup\u003e41,42\u003c/sup\u003e one reported utilization of diagnostic services\u003csup\u003e43\u003c/sup\u003e alone and one reported utilization of both diagnostic and treatment services.\u003csup\u003e40\u003c/sup\u003e Five studies reported costs for MDR-TB care.\u003csup\u003e34,35,37\u0026ndash;39\u003c/sup\u003e Of the five studies that reported treatment outcomes, all but one reported on treatment success. Lost to follow up, death and treatment failure were reported by all five studies (\u003ca href=\"#Study_characteristics\"\u003eTable 2\u003c/a\u003e). \u0026nbsp;\u003c/p\u003e\n\u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cstrong\u003eTable 2.\u003c/strong\u003e \u003cstrong\u003e\u003cspan style=\"color:black;\"\u003eTable showing characteristics of studies on decentralized versus centralized care of MDR-TB in Sub-Saharan Africa\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003ctable style=\"border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 86.6pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;height: 33.15pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003e\u003cstrong\u003eAuthor and year of publication\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 78.7pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;height: 33.15pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e\u003cstrong\u003eCountry\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 94.25pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;height: 33.15pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e\u003cstrong\u003eStudy design\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 95.7pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;height: 33.15pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e\u003cstrong\u003eYear of intervention\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 136.6pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;height: 33.15pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e\u003cstrong\u003eSample size for control/intervention\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 256.65pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;height: 33.15pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e\u003cstrong\u003eDescription of models of care\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 92pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;height: 33.15pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e\u003cstrong\u003eTiming of intervention\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 206.5pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;height: 33.15pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003e\u003cstrong\u003eOutcome(s) measured\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 121.15pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 32.45pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003e\u003cstrong\u003eCentralized\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003e\u003cstrong\u003e(Control)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135.5pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 32.45pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003e\u003cstrong\u003eDecentralized\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003e\u003cstrong\u003e(Intervention)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 86.6pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 73.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003eLoveday et al, 2015\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78.7pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 73.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003eSouth Africa\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94.25pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 73.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003eProspective cohort\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95.7pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 73.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e2008 - 2010\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 136.6pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 73.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e813/736\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121.15pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 73.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003eTreatment at a specialized central hospital\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135.5pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 73.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003eTreatment at a rural hospital followed by outpatient clinic or home-based care\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 73.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003eConcurrent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 206.5pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 73.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003eTreatment outcomes (cure, completion, success, failure, default, death, unsuccessful, transferred out)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 86.6pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 56.7pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003eSharma et al, 2015\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78.7pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 56.7pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003eKenya\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94.25pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 56.7pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003eCross-sectional\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95.7pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 56.7pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e2012 - 2013\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 136.6pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 56.7pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e355/432\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121.15pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 56.7pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003eHospitals referring specimens to a central laboratory\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135.5pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 56.7pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003eHospitals referring specimens to a regional laboratory\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 56.7pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003eConcurrent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 206.5pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 56.7pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003eNumber and proportion of retreatment cases tested; event time when testing retreatment cases in reference laboratory\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 86.6pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 84.15pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003eLoveday et al, 2012\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78.7pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 84.15pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003eSouth Africa\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94.25pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 84.15pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003eProspective cohort\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95.7pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 84.15pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e2008 - 2009\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 136.6pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 84.15pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e441/419\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121.15pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 84.15pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003eTreatment at a centralized specialist hospital followed by outpatient visits at the same facility\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135.5pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 84.15pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003eTreatment at district hospitals followed by outpatient follow-ups by healthcare workers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 84.15pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003eConcurrent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 206.5pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 84.15pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003eProportion of patients who culture converted; time-to-conversion, treatment-initiation-delay, survival\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 86.6pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 84.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003eMolla et al, 2017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 78.7pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 84.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003eEthiopia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 94.25pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 84.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003eInterrupted time series\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 95.7pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 84.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e2012 - 2015\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 136.6pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 84.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e56/790\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121.15pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 84.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003eHospital-based care \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135.5pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 84.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003eAmbulatory-based care\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 84.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003eConsecutive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 206.5pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 84.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003eAccess to MDR-TB service (number of TICs established, number of MDR-TB patients enrolled to treatment); treatment outcomes (cured, completed, failed, lost to follow up, died)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 136.6pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 84.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e662/14,361\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121.15pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 84.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003eDiagnosis at centralized MDR-TB diagnostic centres (two culture centres, no GeneXpert centre)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135.5pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 84.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003eDiagnosis at decentralized MDR-TB diagnrostic centres (5 culture and DST centres, 49 GeneXpert centres)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 84.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003eConsecutive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 206.5pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 84.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003eAccess to MDR-TB service (number of samples tested)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 86.6pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 84.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003eKasozi et al, 2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78.7pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 84.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003eUganda\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94.25pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 84.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003eInterrupted time series\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95.7pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 84.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e2013 - 2017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 136.6pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 84.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e41/1311\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121.15pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 84.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003eTreatment at specialized facilities\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135.5pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 84.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003eTreatment initiated at specialized facilities followed by long periods of ambulatory care\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 84.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003eConsecutive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 206.5pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 84.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003eNumber of treatment initiation sites; number of patients enrolled to treatment; treatment outcomes (cured, completed, lost to follow up, died, failed)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 86.6pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 84.45pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003eEvans et al, 2018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78.7pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 84.45pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003eSouth Africa\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94.25pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 84.45pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003eRetrospective cohort\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95.7pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 84.45pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e2011 - 2014\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 136.6pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 84.45pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e594/713\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121.15pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 84.45pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003eEarly/limited access to Xpert MTB/RIF (i.e 35% decentralization of Xpert MTB/RIF)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135.5pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 84.45pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003eExpanded/full access to Xpert MTB/RIF (i.e \u0026gt;90% access to Xpert MTB/RIF)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 84.45pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003eConsecutive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 206.5pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 84.45pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003eProportion of patients initiated on treatment; time to treatment initiation; treatment outcomes (cured, completed, failure, lost to follow up, death)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 86.6pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 70.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003eMollel et al, 2019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78.7pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 70.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003eTanzania\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94.25pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 70.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003eRetrospective cohort\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95.7pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 70.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e2009 - 2013\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 136.6pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 70.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e14/90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121.15pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 70.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003eDiagnosis by Xpert MTB/RIF and treatment at a single specialized hospital\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135.5pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 70.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003eDiagnosis by Xpert MTB/RIF at 10 peripheral health facilities\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 70.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003eConsecutive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 206.5pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 70.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003eNumber of patients initiated to treatment; time to treatment initiation; treatment outcomes (cured, completed, lost to follow up, failure, death)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 86.6pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 56.7pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003eRamma et al, 2015\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78.7pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 56.7pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003eSouth Africa\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94.25pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 56.7pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003eCost analysis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95.7pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 56.7pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e2013\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 136.6pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 56.7pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e82/52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121.15pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 56.7pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003eHospital-based care \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135.5pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 56.7pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003eAmbulatory-based care\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 56.7pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003eConcurrent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 206.5pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 56.7pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003ePatient costs\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 86.6pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 56.7pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003eAlemayehu et al, 2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78.7pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 56.7pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003eEthiopia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94.25pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 56.7pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003eCost-effectiveness analysis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95.7pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 56.7pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 136.6pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 56.7pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e128/115\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121.15pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 56.7pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003eHospital-based care \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135.5pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 56.7pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003eAmbulatory-based care\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 56.7pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 206.5pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 56.7pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003eHealth system costs\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 86.6pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 77.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003eLoveday et al, 2018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78.7pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 77.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003eSouth Africa\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94.25pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 77.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003eCost-effectiveness analysis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95.7pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 77.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e2008 - 2010\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 136.6pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 77.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e582/70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121.15pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 77.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003eTreatment at a specialized central hospital\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135.5pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 77.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003eTreatment at community-based clinic or by mobile healthcare provider team\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 77.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003eConcurrent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 206.5pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 77.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003eHealth system costs; treatment outcomes (cured, completed, success, died, failed, defaulted, transferred out)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 86.6pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 56.7pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003eBada et al, 2019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78.7pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 56.7pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003eNigeria\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94.25pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 56.7pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003eCost analysis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95.7pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 56.7pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e2013 - 2014\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 136.6pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 56.7pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121.15pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 56.7pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003eHospital-based care \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135.5pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 56.7pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003eCommunity-based DOT by trained provider\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 56.7pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003eConcurrent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 206.5pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 56.7pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003eHealth system costs\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 86.6pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 70.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003eBada et al, 2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78.7pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 70.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003eNigeria\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94.25pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 70.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003eCost analysis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95.7pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 70.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 136.6pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 70.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121.15pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 70.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003eHospitalization followed by outpatient visits for DOT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135.5pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 70.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003eAmbulatory-mode of care through home-based DOT or clinic-based DOT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 70.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 206.5pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 70.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003eHealth system costs\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;'\u003eNR \u0026ndash; Not reported \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n\u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003eN/A \u0026ndash; Not applicable\u003c/p\u003e\n\u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003e\u003cbr\u003e\u003c/p\u003e\n\u003ch2\u003e\u003cstrong\u003eAccess to MDR-TB services\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/h2\u003e\n\u003ch3\u003e\u003cem\u003eUtilization of MDR-TB diagnostic services\u0026nbsp;\u003c/em\u003e\u003c/h3\u003e\n\u003cp\u003eTwo studies which assessed the effect of decentralizing MDR-TB diagnostic services on their utilization, noted increases in the number of samples tested when diagnostic services were decentralized.\u003csup\u003e40,41,43\u003c/sup\u003e The Kenyan study conducted by Sharma \u003cem\u003eet al\u003c/em\u003e between 2012 and 2013, found that a higher number of patients (n = 238) registered in hospitals referring to the regional laboratory underwent Drug Susceptibility Testing\u003ca href=\"#_ftn1\" name=\"_ftnref1\" title=\"\"\u003e[3]\u003c/a\u003e (DST) compared to those registered in hospitals referring to the central laboratory (n = 88) (\u003ca href=\"#Utilization_of_MDRTB_services\"\u003eTable 3\u003c/a\u003e).\u003csup\u003e43\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSimilarly, an increase in number of patients tested for MDR-TB was noted by Molla and colleagues between 2012 and 2015 in Ethiopia.\u003csup\u003e40\u003c/sup\u003e At baseline, in 2012, only two centres which could perform culture for MDR-TB existed and no GeneXpert machines (machines used to diagnose TB and detect drug-resistance) were available.\u003csup\u003e40\u003c/sup\u003e At the end of the program, 2015, five laboratories were equipped for liquid culture and DST and 49 GeneXpert centres existed.\u003csup\u003e40\u003c/sup\u003e This led to an increase in the number of samples tested per year, from 662 in 2012 to 14,361 in 2015 (\u003ca href=\"#Utilization_of_MDRTB_services\"\u003eTable 3\u003c/a\u003e).\u003csup\u003e40\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003ch3\u003e\u003cem\u003eUtilization of MDR-TB treatment services\u0026nbsp;\u003c/em\u003e\u003c/h3\u003e\n\u003cp\u003eTwo out of three studies that examined the effect of decentralizing MDR-TB treatment services reported an increase in the number of enrolled patients after decentralization.\u003csup\u003e40,42\u003c/sup\u003e Kasozi and colleagues noted that only three sites were able to initiate MDR-TB treatment in 2012, prior to expanding treatment initiating facilities and allowing outpatient DOT.\u003csup\u003e42\u003c/sup\u003e At the end of the intervention, in 2017, treatment could be initiated at 15 sites.\u003csup\u003e42\u003c/sup\u003e This increased the number of patients enrolled into care from 41 at baseline (2012) to over 200 patients every year, amounting to a cumulative total of 1311 patients enrolled into care in 2017 (\u003ca href=\"#Utilization_of_MDRTB_services\"\u003eTable 3\u003c/a\u003e).\u003csup\u003e42\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn the Ethiopian study, 56 patients were enrolled for treatment in the only available MDR-TB treatment initiating facility at baseline (2012).\u003csup\u003e40\u003c/sup\u003e At the end of the program in 2015, a cumulative total of 790 patients were enrolled for MDR-TB treatment from 23 established facilities with, 155, 254 and 325 patients enrolled in the years 2013, 2014 and 2015 respectively.\u003csup\u003e40\u003c/sup\u003e A study conducted in Tanzania by Mollel \u003cem\u003eet al\u003c/em\u003e, 2019, reported an increase in the number of patients enrolled into care from 14 to 90 when diagnostic services (Xpert MTB/RIF machines) were decentralized to 10 peripheral facilities in 2013 (Table 3).\u003csup\u003e41\u003c/sup\u003e Prior to decentralization, patient enrolment into care relied on DST results from the Central Tuberculosis Reference Laboratory.\u003csup\u003e41\u003c/sup\u003e\u003c/p\u003e\n\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:12px;font-family:\"Times New Roman\",serif;color:#44546A;font-style:italic;line-height:200%;'\u003e\u003cstrong\u003e\u003cspan style=\"font-size:16px;line-height:200%;color:black;font-style:normal;\"\u003eTable 3: Table showing MDR-TB service utilization in centralized and decentralized models\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003ctable style=\"width:538.85pt;border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108.6pt;border-right: none;border-bottom: none;border-left: none;border-image: initial;border-top: 1pt solid windowtext;padding: 0in 5.4pt;height: 33.15pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003e\u003cstrong\u003e\u003cspan style=\"font-size:15px;line-height:150%;\"\u003eStudy\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78.3pt;border-right: none;border-bottom: none;border-left: none;border-image: initial;border-top: 1pt solid windowtext;padding: 0in 5.4pt;height: 33.15pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e\u003cstrong\u003e\u003cspan style=\"font-size:15px;line-height:150%;\"\u003eStudy design\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62pt;border-right: none;border-bottom: none;border-left: none;border-image: initial;border-top: 1pt solid windowtext;padding: 0in 5.4pt;height: 33.15pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e\u003cstrong\u003e\u003cspan style=\"font-size:15px;line-height:150%;\"\u003eCountry\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 145.8pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;height: 33.15pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e\u003cstrong\u003e\u003cspan style=\"font-size:15px;line-height:150%;\"\u003eUtilization of services\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108.6pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 30pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003e\u003cstrong\u003e\u003cspan style=\"font-size:15px;line-height:150%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78.3pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 30pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e\u003cspan style=\"font-size:15px;line-height:150%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 30pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e\u003cspan style=\"font-size:15px;line-height:150%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.25pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 30pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e\u003cstrong\u003e\u003cspan style=\"font-size:15px;line-height:150%;\"\u003eCentralized (n)\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75.55pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;height: 30pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e\u003cstrong\u003e\u003cspan style=\"font-size:15px;line-height:150%;\"\u003eDecentralized (n)\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" style=\"width: 394.7pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 30pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e\u003cstrong\u003e\u003cspan style=\"font-size:15px;line-height:150%;\"\u003eUtilization of diagnostic services (number of samples tested for MDR-TB)\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108.6pt;border: none;padding: 0in 5.4pt;height: 30pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003e\u003cspan style=\"font-size:15px;line-height:150%;\"\u003eSharma et al, 2015\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78.3pt;border: none;padding: 0in 5.4pt;height: 30pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e\u003cspan style=\"font-size:15px;line-height:150%;\"\u003eCross-sectional\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62pt;border: none;padding: 0in 5.4pt;height: 30pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e\u003cspan style=\"font-size:15px;line-height:150%;\"\u003eKenya\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.25pt;border: none;padding: 0in 5.4pt;height: 30pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e\u003cspan style=\"font-size:15px;line-height:150%;\"\u003e88\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75.55pt;border: none;padding: 0in 5.4pt;height: 30pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e\u003cspan style=\"font-size:15px;line-height:150%;\"\u003e238\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108.6pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 30pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003e\u003cspan style=\"font-size:15px;line-height:150%;\"\u003eMolla et al, 2017\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78.3pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 30pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e\u003cspan style=\"font-size:15px;line-height:150%;\"\u003eInterrupted time series\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 30pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e\u003cspan style=\"font-size:15px;line-height:150%;\"\u003eEthiopia\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.25pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 30pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e\u003cspan style=\"font-size:15px;line-height:150%;\"\u003e662\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75.55pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 30pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e\u003cspan style=\"font-size:15px;line-height:150%;\"\u003e14361\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" style=\"width: 394.7pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 30pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e\u003cstrong\u003e\u003cspan style=\"font-size:15px;line-height:150%;\"\u003eUtilization of treatment services (number of patients enrolled into MDR-TB care)\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108.6pt;border: none;padding: 0in 5.4pt;height: 30pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003e\u003cspan style=\"font-size:15px;line-height:150%;\"\u003eKasozi et al, 2020\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78.3pt;border: none;padding: 0in 5.4pt;height: 30pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e\u003cspan style=\"font-size:15px;line-height:150%;\"\u003eInterrupted time series\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62pt;border: none;padding: 0in 5.4pt;height: 30pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e\u003cspan style=\"font-size:15px;line-height:150%;\"\u003eUganda\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.25pt;border: none;padding: 0in 5.4pt;height: 30pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e\u003cspan style=\"font-size:15px;line-height:150%;\"\u003e41\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75.55pt;border: none;padding: 0in 5.4pt;height: 30pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e\u003cspan style=\"font-size:15px;line-height:150%;\"\u003e1311\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108.6pt;border: none;padding: 0in 5.4pt;height: 30pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003e\u003cspan style=\"font-size:15px;line-height:150%;\"\u003eMollel et al, 2019\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78.3pt;border: none;padding: 0in 5.4pt;height: 30pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e\u003cspan style=\"font-size:15px;line-height:150%;\"\u003eRetrospective cohort\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62pt;border: none;padding: 0in 5.4pt;height: 30pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e\u003cspan style=\"font-size:15px;line-height:150%;\"\u003eTanzania\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.25pt;border: none;padding: 0in 5.4pt;height: 30pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e\u003cspan style=\"font-size:15px;line-height:150%;\"\u003e14\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75.55pt;border: none;padding: 0in 5.4pt;height: 30pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e\u003cspan style=\"font-size:15px;line-height:150%;\"\u003e90\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108.6pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 30pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:150%;'\u003e\u003cspan style=\"font-size:15px;line-height:150%;\"\u003eMolla et al, 2017\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78.3pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 30pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e\u003cspan style=\"font-size:15px;line-height:150%;\"\u003eInterrupted time series\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 30pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e\u003cspan style=\"font-size:15px;line-height:150%;\"\u003eEthiopia\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.25pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 30pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e\u003cspan style=\"font-size:15px;line-height:150%;\"\u003e56\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75.55pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 30pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;line-height:150%;'\u003e\u003cspan style=\"font-size:15px;line-height:150%;\"\u003e790\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003e\u003cspan style=\"font-size:13px;line-height:200%;\"\u003en = number of samples tested for MDR-TB or number of patients enrolled into MDR-TB care\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003e\u003cbr\u003e\u003c/p\u003e\n\u003ch3\u003e\u003cem\u003eCost of MDR-TB care\u003c/em\u003e\u003c/h3\u003e\n\u003cp\u003eStudies suggested that lower treatment costs were related to decentralized services than centralized services. Three studies, from Ethiopia, Nigeria and South Africa, noted that treatment costs per patient was lower by 24.9%, 48.8% and 54.6% in the three countries, respectively, when ambulatory care was compared to hospital-based care (\u003ca href=\"#Cost_of_MDRTB_services\"\u003eTable 4\u003c/a\u003e).\u003csup\u003e34,37,39\u003c/sup\u003e The same was noted by two studies comparing treatment costs between hospital-based and community-based approaches. These studies noted that 77.7% and 49.1% less cost was incurred when treatment was offered using community-based models than using centralized models in South Africa and Nigeria, respectively (\u003ca href=\"#Cost_of_MDRTB_services\"\u003eTable 4\u003c/a\u003e).\u003csup\u003e35,38\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe study from Ethiopia also compared the cost-effectiveness between hospital-based and ambulatory-based models of care. Alemayehu and colleagues, 2020, reported that the average cost per DALY averted was $671 for an ambulatory treatment approach while for a hospital-based approach it was $1,417 per DALY averted.\u003csup\u003e39\u003c/sup\u003e\u003c/p\u003e\n\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:12px;font-family:\"Times New Roman\",serif;color:#44546A;font-style:italic;'\u003e\u003cstrong\u003e\u003cspan style=\"font-size:16px;color:black;font-style:normal;\"\u003eTable 4: Table showing costs for MDR-TB care in decentralized and centralized models\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003ctable style=\"width: 5.7e+2pt;border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 61.6pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cstrong\u003e\u003cspan style=\"font-size:15px;\"\u003eStudy\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 68.25pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cstrong\u003e\u003cspan style=\"font-size:15px;\"\u003eStudy design\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 50.55pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cstrong\u003e\u003cspan style=\"font-size:15px;\"\u003eCountry\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 161.2pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;'\u003e\u003cstrong\u003e\u003cspan style=\"font-size:15px;\"\u003eCentralized care\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;'\u003e\u003cspan style=\"font-size:15px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 147.4pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;'\u003e\u003cstrong\u003e\u003cspan style=\"font-size:15px;\"\u003eDecentralized care\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 78pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;'\u003e\u003cstrong\u003e\u003cspan style=\"font-size:15px;\"\u003eDifference in cost per-patient (centralized vs decentralized care)\u003c/span\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan style=\"font-size:15px;font-family:Symbol;\"\u003e*\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 87.45pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;'\u003e\u003cstrong\u003e\u003cspan style=\"font-size:15px;\"\u003eDescription\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73.75pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;'\u003e\u003cstrong\u003e\u003cspan style=\"font-size:15px;\"\u003eCost (US$/patient)\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73.65pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cstrong\u003e\u003cspan style=\"font-size:15px;\"\u003eDescription\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73.75pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;'\u003e\u003cstrong\u003e\u003cspan style=\"font-size:15px;\"\u003eCost (US$/patient)\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 61.6pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"font-size:15px;\"\u003eRamma et al, 2015\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68.25pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"font-size:15px;\"\u003eCost analysis from a patient\u0026apos;s perspective\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 50.55pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"font-size:15px;\"\u003eSouth Africa\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 87.45pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;'\u003e\u003cspan style=\"font-size:15px;\"\u003eHospital-based care\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73.75pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;'\u003e\u003cspan style=\"font-size:15px;\"\u003e269.2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73.65pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"font-size:15px;\"\u003eAmbulatory-based care\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73.75pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;'\u003e\u003cspan style=\"font-size:15px;\"\u003e122.1\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;'\u003e\u003cspan style=\"font-size:15px;color:black;\"\u003e-54.6%\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;'\u003e\u003cspan style=\"font-size:15px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 61.6pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"font-size:15px;\"\u003eAlemayehu et al, 2020\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 68.25pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"font-size:15px;\"\u003eCost-effectiveness analysis from a provider\u0026apos;s perspective\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 50.55pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"font-size:15px;\"\u003eEthiopia\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 87.45pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;'\u003e\u003cspan style=\"font-size:15px;\"\u003eHospital-based care (HIV positive)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73.75pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;'\u003e\u003cspan style=\"font-size:15px;\"\u003e1922\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73.65pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"font-size:15px;\"\u003eAmbulatory-based care (HIV positive)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73.75pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;'\u003e\u003cspan style=\"font-size:15px;\"\u003e1443\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;'\u003e\u003cspan style=\"font-size:15px;color:black;\"\u003e-24.9%\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;'\u003e\u003cspan style=\"font-size:15px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 87.45pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;'\u003e\u003cspan style=\"font-size:15px;\"\u003eHospital-based care (HIV negative)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73.75pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;'\u003e\u003cspan style=\"font-size:15px;\"\u003e1798\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73.65pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"font-size:15px;\"\u003eAmbulatory-based care (HIV negative)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73.75pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;'\u003e\u003cspan style=\"font-size:15px;\"\u003e1391\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;'\u003e\u003cspan style=\"font-size:15px;color:black;\"\u003e-22.6%\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;'\u003e\u003cspan style=\"font-size:15px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 61.6pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"font-size:15px;\"\u003eLoveday et al, 2018\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 68.25pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"font-size:15px;\"\u003eCost-effectiveness analysis from a provider\u0026apos;s perspective\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 50.55pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"font-size:15px;\"\u003eSouth Africa\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 87.45pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;'\u003e\u003cspan style=\"font-size:15px;\"\u003eTreatment at a specialized central hospital\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 73.75pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;'\u003e\u003cspan style=\"font-size:15px;\"\u003e30185\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73.65pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"font-size:15px;\"\u003eTreatment at community-based clinic\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73.75pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;'\u003e\u003cspan style=\"font-size:15px;\"\u003e6739\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;'\u003e\u003cspan style=\"font-size:15px;color:black;\"\u003e-77.7%\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;'\u003e\u003cspan style=\"font-size:15px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73.65pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"font-size:15px;\"\u003eTreatment at community-by mobile healthcare provider team\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73.75pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;'\u003e\u003cspan style=\"font-size:15px;\"\u003e9394\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;'\u003e\u003cspan style=\"font-size:15px;color:black;\"\u003e-68.9%\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;'\u003e\u003cspan style=\"font-size:15px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 61.6pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"font-size:15px;\"\u003eBada et al, 2019\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68.25pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"font-size:15px;\"\u003eCost analysis from a provider\u0026apos;s perspective\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 50.55pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"font-size:15px;\"\u003eNigeria\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 87.45pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;'\u003e\u003cspan style=\"font-size:15px;\"\u003eHospital-based care\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73.75pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;'\u003e\u003cspan style=\"font-size:15px;\"\u003e18528\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73.65pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"font-size:15px;\"\u003eCommunity-based DOT by trained provider\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73.75pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;'\u003e\u003cspan style=\"font-size:15px;\"\u003e9424\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;'\u003e\u003cspan style=\"font-size:15px;color:black;\"\u003e-49.1%\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;'\u003e\u003cspan style=\"font-size:15px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 61.6pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"font-size:15px;\"\u003eBada et al, 2020\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 68.25pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"font-size:15px;\"\u003eCost analysis from a provider\u0026apos;s perspective\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 50.55pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"font-size:15px;\"\u003eNigeria\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 87.45pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;'\u003e\u003cspan style=\"font-size:15px;\"\u003e8month hospitalization followed by 12 months of outpatient care\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73.75pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;'\u003e\u003cspan style=\"font-size:15px;\"\u003e14781\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73.65pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"font-size:15px;\"\u003eA fully ambulatory model for 20 months\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73.75pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;'\u003e\u003cspan style=\"font-size:15px;\"\u003e7572\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;'\u003e\u003cspan style=\"font-size:15px;color:black;\"\u003e-48.8%\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;'\u003e\u003cspan style=\"font-size:15px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 87.45pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;'\u003e\u003cspan style=\"font-size:15px;\"\u003e4months hospitalization followed by 5 - 8 months of outpatient care\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73.75pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;'\u003e\u003cspan style=\"font-size:15px;\"\u003e7705\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73.65pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"font-size:15px;\"\u003eA fully ambulatory model for 9 - 12 months\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73.75pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;'\u003e\u003cspan style=\"font-size:15px;\"\u003e4334\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;'\u003e\u003cspan style=\"font-size:15px;color:black;\"\u003e-43.8%\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;text-align:center;'\u003e\u003cspan style=\"font-size:15px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cspan style=\"font-size:13px;font-family:Symbol;\"\u003e*\u003c/span\u003e\u003cspan style='font-size:13px;font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;- Difference = (Cost in decentralized \u0026ndash; Cost in centralized model) / Cost in centralized model\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003ch2\u003e\u003cstrong\u003eMDR-TB treatment outcomes\u0026nbsp;\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003e\u003ca href=\"#Treatment_outcomes\"\u003eTable 5\u003c/a\u003e summarizes prevalence estimates for each treatment outcome for the centralized and decentralized models.\u0026nbsp;\u003c/p\u003e\n\u003ch3\u003e\u003cem\u003eTreatment success\u0026nbsp;\u003c/em\u003e\u003c/h3\u003e\n\u003cp\u003eTwo prospective cohort studies conducted by Loveday and colleagues in KwaZulu-Natal (KZN), South Africa in 2015 and 2018 reported higher treatment success estimates for the decentralized model of care than the centralized model.\u003csup\u003e11,35\u003c/sup\u003e In these studies, treatment success for the centralized model were estimated to be 54% and 54.1%, respectively.\u003csup\u003e11,35\u003c/sup\u003e Treatment success for the decentralized model were estimated to be 58% in 2015 and 64.3% in 2018.\u003csup\u003e11,35\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTwo studies, however, found reduced treatment success estimates with decentralized models compared to a centralized model. Evans \u003cem\u003eet al\u003c/em\u003e, 2018, noted 32.9% of those treated by a centralized model were successfully treated while 29.6% of those treated by a decentralized model were successfully treated.\u003csup\u003e33\u003c/sup\u003e Kasozi \u003cem\u003eet al\u003c/em\u003e, 2020, reported that 78% of patients were successfully treated at baseline (2012) while the overall treatment success estimate reduced to 72.6% during the decentralization program in 2015.\u003csup\u003e42\u003c/sup\u003e However, proportions from the Ugandan study are from a population of 41 patients at baseline and 649 patients enrolled to treatment during decentralization (2013 \u0026ndash; 2015).\u003csup\u003e42\u003c/sup\u003e In the three years of decentralization, the program consistently noted high success rates (73.9%, 2013; 74.1%, 2014; and 70.1%, 2015) even with increasing population sizes.\u003csup\u003e42\u003c/sup\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003ch3\u003e\u003cem\u003eLost to follow-up (LTFU)\u003c/em\u003e\u003c/h3\u003e\n\u003cp\u003eThree studies by Loveday \u003cem\u003eet al\u003c/em\u003e, in 2012, 2015 and 2018 reported reduced estimates of LTFU for decentralized treatment approaches compared to a centralized approach.\u003csup\u003e11,35,36\u003c/sup\u003e In two of the studies, LTFU estimates of patients treated in decentralized facilities were nearly half of those treated in a centralized hospital (14.5% vs 28.3%, 2015 and 12.9% vs 24.9%, 2018).\u003csup\u003e11,35\u003c/sup\u003e In the 2012 study, 18.9% of patients treated in decentralized facilities were lost to follow-up while those treated in a centralized hospital and were lost to follow-up was 30.2%.\u003csup\u003e36\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eKasozi \u003cem\u003eet al\u003c/em\u003e and Evans \u003cem\u003eet al\u003c/em\u003e, reported similar estimates of LTFU for the two approaches. Kasozi \u003cem\u003eet al\u003c/em\u003e, reported that 9.8% and 10.9% of patients were LTFU before decentralization and after three years of decentralizing MDR-TB services, respectively.\u003csup\u003e42\u003c/sup\u003e Evans \u003cem\u003eet al\u003c/em\u003e, reported that 55.3% of patients utilizing the centralized model were LTFU while 55.9% of patients under the decentralized model were LTFU.\u003csup\u003e33\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003ch3\u003e\u003cem\u003eDeath\u0026nbsp;\u003c/em\u003e\u003c/h3\u003e\n\u003cp\u003eLoveday \u003cem\u003eet al\u003c/em\u003e, in 2012, reported that 6.8% of patients under centralized care died while 16% of patients under decentralized care died.\u003csup\u003e36\u003c/sup\u003e Kasozi \u003cem\u003eet al\u003c/em\u003e, 2020, noted that 5% of patients receiving treatment under the centralized model died while 15% of those receiving treatment using the decentralized model died.\u003csup\u003e42\u003c/sup\u003e While Loveday \u003cem\u003eet al,\u0026nbsp;\u003c/em\u003e2015 and Evans \u003cem\u003eet al,\u0026nbsp;\u003c/em\u003e2020 also reported higher death estimates among patients treated using a decentralized model, these differences were not shown to be statistically significant.\u003csup\u003e11,33\u003c/sup\u003e According to Loveday \u003cem\u003eet al\u003c/em\u003e in 2015, 14% of patients using the centralized model died while 18% of those using the decentralized model died.\u003csup\u003e11\u003c/sup\u003e Also, 12% of patients receiving centralized care died while 14% of those receiving decentralized care died, as reported in 2020 by Evans \u003cem\u003eet al.\u003c/em\u003e\u003csup\u003e33\u003c/sup\u003e Being HIV positive with MDR-TB and not on antiretroviral therapy (ART) was associated with these high death estimates.\u003csup\u003e11,33\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003ch3\u003e\u003cem\u003eTreatment failure\u0026nbsp;\u003c/em\u003e\u003c/h3\u003e\n\u003cp\u003eSimilar treatment failure estimates between the two treatment models were reported by Evans \u003cem\u003eet al\u003c/em\u003e and Kasozi \u003cem\u003eet al.\u0026nbsp;\u003c/em\u003eBoth studies reported no treatment failure before decentralization and 0.3% and 1.1% failure estimates after decentralization, respectively.\u003csup\u003e33,42\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThree studies by Loveday \u003cem\u003eet al\u003c/em\u003e reported increased treatment failure estimates for the decentralized model compared to centralized model. In 2012, the authors noted no patient (0.0%) failing treatment in the centralized group while 15 (3.6%) patients failed treatment in the decentralized group.\u003csup\u003e36\u003c/sup\u003e Also, in 2015, the authors noted that 3.6% of patients failed treatment in the centralized group while 6.7% of patients in the decentralized group failed treatment.\u003csup\u003e11\u003c/sup\u003e Although, increased estimates of failing treatment were also reported in 2018 by Loveday \u003cem\u003eet al\u003c/em\u003e (3.3% in centralized group vs 7.1% in decentralized group), the sample size of the two groups differed significantly (582 vs 70 respectively).\u003csup\u003e35\u003c/sup\u003e\u003c/p\u003e\n\u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;'\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eTable 5.\u003c/span\u003e\u003c/strong\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003cstrong\u003eTable showing\u003c/strong\u003e \u003cstrong\u003eprevalence estimates of treatment outcomes for patients treated using decentralized and centralized approaches\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"width: 9.1e+2pt;border: none;border-collapse:collapse;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width: 70.9pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eStudy\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" style=\"width: 368.55pt;border-right: none;border-bottom: none;border-left: none;border-image: initial;border-top: 1pt solid windowtext;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cstrong\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003eCentralized care\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.85pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cstrong\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" style=\"width: 326.05pt;border-right: none;border-bottom: none;border-left: none;border-image: initial;border-top: 1pt solid windowtext;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cstrong\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003eDecentralized care\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.85pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cstrong\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 56.7pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cstrong\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003eTotal patients\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 311.85pt;border-right: none;border-bottom: none;border-left: none;border-image: initial;border-top: 1pt solid windowtext;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cstrong\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003eNumber of patients (%)\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.85pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cstrong\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 56.7pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cstrong\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003eTotal patients\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 269.35pt;border: none;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cstrong\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003eNumber of patients (%)\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.85pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cstrong\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 1.15in;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cstrong\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003eTreatment success\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80.2pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cstrong\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003eLost to follow up\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.9pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cstrong\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003eDeath\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cstrong\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003eTreatment failure\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.85pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cstrong\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003eOthers\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.9pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cstrong\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003eTreatment success\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cstrong\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003eLost to follow up\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.75pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cstrong\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003eDeath\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.9pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cstrong\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003eTreatment failure\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.85pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cstrong\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003eOthers\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 70.9pt;border: none;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eLoveday et al, 2015\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border: none;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003e813\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 1.15in;border: none;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003e439 (54)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80.2pt;border: none;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003e230 (28.3)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.9pt;border: none;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003e113 (13.9)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;border: none;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003e29 (3.6)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.85pt;border: none;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003e2 (0.2)\u003csup\u003ea\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border: none;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003e736\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.9pt;border: none;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003e427 (58.0)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;border: none;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003e107 (14.5)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.75pt;border: none;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003e133 (18.1)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.9pt;border: none;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003e49 (6.7)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.85pt;border: none;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003e20 (2.7)\u003csup\u003ea\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 70.9pt;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eLoveday et al, 2012\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003e441\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 1.15in;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003eONA\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80.2pt;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003e133 (30.2)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.9pt;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003e30 (6.8)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003e0 (0.0)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.85pt;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003e278 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style='font-family: \"Times New Roman\",serif;'\u003e258 (61.6)\u003csup\u003eb\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 70.9pt;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eKasozi et al, 2020*\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003e41\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 1.15in;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003e32 (78.0)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80.2pt;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003e4 (9.8)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.9pt;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003e2 (4.9)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n 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50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003e471 (72.6)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003e71 (10.9)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.75pt;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003e100 (15.4)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.9pt;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003e7 (1.1)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.85pt;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003e0 (0.0)\u003csup\u003ec\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 70.9pt;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eEvans et al, 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style='font-family: \"Times New Roman\",serif;'\u003e204 (55.9)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.75pt;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003e52 (14.2)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.9pt;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003e1 (0.3)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.85pt;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 70.9pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eLoveday et al, 2018\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003e582\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 1.15in;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003e315 (54.1)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80.2pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003e145 (24.9)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.9pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003e101 (17.4)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003e19 (3.3)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.85pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003e2 (0.3)\u003csup\u003ea\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003e70\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.9pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003e45 (64.3)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003e9 (12.9)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.75pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003e8 (11.4)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.9pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003e5 (7.1)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.85pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 50pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:150%;'\u003e\u003cspan style='font-family: \"Times New Roman\",serif;'\u003e3 (4.3)\u003csup\u003ea\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;'\u003e\u003csup\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ea\u003c/span\u003e\u003c/sup\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u0026ndash; Transferred out\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;'\u003e\u003csup\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eb\u003c/span\u003e\u003c/sup\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u0026ndash; Still on treatment\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;'\u003e\u003csup\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ec\u003c/span\u003e\u003c/sup\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u0026ndash; Not evaluated\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e* - Outcomes up until 2015 only, study ended in 2017 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003eONA - Outcome Not Assessed\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cdiv id=\"ftn1\"\u003e\n \u003cp\u003e\u003ca href=\"#_ftnref1\" name=\"_ftn1\" title=\"\"\u003e[3]\u003c/a\u003e Drug-susceptibility testing refers to in-vitro testing using either phenotypic methods to determine susceptibility or molecular techniques to detect resistance-conferring mutations to a medicine.\u003csup\u003e7\u003c/sup\u003e\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis review aimed to examine the effect of decentralizing MDR-TB services on the accessibility of services and patient treatment outcomes in sub-Saharan Africa. Findings from this study suggest that decentralizing MDR-TB care in SSA has improved access to services through increased utilization of MDR-TB services and reduction of MDR-TB treatment cost. Findings also suggest that decentralizing MDR-TB services has contributed to increased successful treatment and retention of patients to care.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003e\u003cstrong\u003eAccess to MDR-TB services \u0026nbsp;\u0026nbsp;\u003c/strong\u003e\u003c/h2\u003e\n\u003ch3\u003e\u003cem\u003eUtilization of diagnostic and treatment services\u003c/em\u003e\u003c/h3\u003e\n\u003cp\u003eAll studies included in this review reported higher numbers of patients accessing and utilizing decentralized MDR-TB diagnostic and treatment services than centralized services.\u003csup\u003e40\u0026ndash;43\u003c/sup\u003e\u0026nbsp; \u0026nbsp;Similar findings are reported by studies conducted in other low- and middle-income countries (LMICs) such as Peru, Bangladesh and Myanmar.\u003csup\u003e44\u0026ndash;46\u003c/sup\u003e This enriches the evidence of the vital importance of decentralized approaches in ensuring MDR-TB patient\u0026rsquo;s access to services in resource limited settings such as those of SSA. \u0026nbsp;Widespread availability of MDR-TB diagnostic and treatment services after decentralization is reason for the higher numbers accessing and utilizing services.\u003csup\u003e40,42,43\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003ch3\u003e\u003cem\u003eCost of MDR-TB treatment\u003c/em\u003e\u003c/h3\u003e\n\u003cp\u003eAll cost studies included in this review suggested that MDR-TB care using decentralized approaches is less costly than using centralized approaches.\u003csup\u003e34,35,37\u0026ndash;39\u003c/sup\u003e Alemayehu \u003cem\u003eet al\u003c/em\u003e, 2020, the only study which reported cost-effectiveness using economic models, also suggested that decentralized care is more cost-effective than centralized care.\u003csup\u003e39\u003c/sup\u003e These findings are consistent with other systematic reviews conducted by Fitzpatrick C. and Floyd K, and Ho \u003cem\u003eet al.\u003c/em\u003e\u003csup\u003e9,47\u003c/sup\u003e Findings from the current review, therefore, imply that decentralization of MDR-TB services can be operationalized at affordable costs in the sub-Saharan setting. However, most cost-analyses included in this review did not capture MDR-TB patient\u0026rsquo;s costs.\u003csup\u003e35,37\u0026ndash;39\u003c/sup\u003e The only study to do so noted that, even patients using ambulatory approaches can face catastrophic costs and calls for socio-economic support systems to be in place.\u003csup\u003e34\u003c/sup\u003e While the major cost driver for centralized care was hospitalization, for decentralized care was outpatient consultation and supervision.\u003csup\u003e34,38\u003c/sup\u003e Using decentralized care, however, has an added benefit of preserving patient\u0026rsquo;s social support structure and earlier treatment initiation.\u003csup\u003e38\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003e\u003cstrong\u003eMDR-TB treatment outcomes\u0026nbsp;\u003c/strong\u003e\u003c/h2\u003e\n\u003ch3\u003e\u003cem\u003eTreatment success\u0026nbsp;\u003c/em\u003e\u003c/h3\u003e\n\u003cp\u003eSuccess rates in some studies were found to be higher for decentralized model of care than for the centralized model.\u003csup\u003e11,35,40\u003c/sup\u003e A critical step in ensuring this achievement was noted to be early detection and management through strengthening technical and infrastructure capacity.\u003csup\u003e40\u003c/sup\u003e Similar results were reported by previous studies assessing treatment outcomes for decentralized models.\u003csup\u003e48,49\u003c/sup\u003e While support from external organizations (e.g. international donors) contributed to the success rate in these studies by offering comprehensive treatment packages, some studies included in this review reported no external support for the decentralization program.\u003csup\u003e11,48,49\u003c/sup\u003e This implies that decentralization of MDR-TB services can successfully be implemented in resource limited settings such as those of SSA to achieve MDR-TB treatment success.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn contrast, Kasozi and colleagues reported, in their interrupted time series, a reduction in overall treatment success estimates during a decentralization program.\u003csup\u003e42\u003c/sup\u003e Despite this reduction, the program was able to maintain high levels of treatment success amidst the large expansion in patient volumes.\u003csup\u003e42\u003c/sup\u003e This suggests that governments within sub-Saharan Africa can maintain high treatment success rates even with increased patient numbers. This can be achieved by implementing continuous quality improvement strategies such as peer-to-peer mentorships and holding learning sessions as applied in Uganda.\u003csup\u003e42\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003ch3\u003e\u003cem\u003eLost to follow up\u0026nbsp;\u003c/em\u003e\u003c/h3\u003e\n\u003cp\u003eDecentralized MDR-TB care was related to lower estimates of LTFU in most studies conducted in South Africa.\u003csup\u003e11,35,36\u003c/sup\u003e Contrastingly, a study in Uganda reported similar estimates of LTFU between the two approaches.\u003csup\u003e42\u003c/sup\u003e This difference could be attributed to low capacity and lack of experience in MDR-TB management of selected sites during decentralization in Uganda.\u003csup\u003e42\u003c/sup\u003e Similar LTFU estimates between the two treatment approaches were also reported by Evans \u003cem\u003eet al\u003c/em\u003e in South Africa.\u003csup\u003e33\u003c/sup\u003e In agreement with these findings are systematic reviews and meta-analyses conducted by Bassili \u003cem\u003eet al\u003c/em\u003e and Ho \u003cem\u003eet al\u003c/em\u003e.\u003csup\u003e9,22\u003c/sup\u003e Therefore, decentralization of MDR-TB in SSA, has potential to reduce estimates of LTFU when treatment sites are adequately capacitated. \u0026nbsp;\u003c/p\u003e\n\u003ch3\u003e\u003cem\u003eDeath\u003c/em\u003e\u003c/h3\u003e\n\u003cp\u003eWhile most studies in this review reported higher death estimates among patients in decentralized sites than in centralized site,\u003csup\u003e11,36,42\u003c/sup\u003e only one study reported a statistically significant difference.\u003csup\u003e36\u003c/sup\u003e The difference noted in this study is reported to have been probably due to missing data in registers from which data was extracted at centralized sites.\u003csup\u003e36\u003c/sup\u003e This may have led to underestimation of death estimates at the centralized site. Despite the observation in the Ugandan study, there was a large difference between the sample sizes of the two arms (centralized arm; 41 patients vs decentralized arm; 649 patients), from which estimates were calculated.\u003csup\u003e42\u003c/sup\u003e Consequently, the noted difference in death estimates seems to be insignificant, as with findings from some studies included in this review and other systematic reviews.\u003csup\u003e9,11,22,33\u003c/sup\u003e\u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003ch3\u003e\u003cem\u003eTreatment failure\u0026nbsp;\u003c/em\u003e\u003c/h3\u003e\n\u003cp\u003eConsistent with findings from other studies, estimates of MDR-TB treatment failure for decentralized and centralized care were found to be similar in some studies included in this review.\u003csup\u003e9,33,42,50\u003c/sup\u003e However, other studies included in this review reported higher estimates of treatment failure in decentralized settings than in centralized settings.\u003csup\u003e11,36\u003c/sup\u003e Even with these observed differences, reported estimates did not exceed the global treatment failure estimate.\u003csup\u003e2\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003e\u003cstrong\u003eStudy strengths and limitations\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003eStrengths of this review include, a comprehensive literature search from scientific databases and using strict eligibility criteria to limit the review to studies with patients receiving a decentralized and centralized care. This allowed studies to be selected without bias and comparisons be made from same population groups in similar settings.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis review also had several limitations. Grey literature was not included in the review as it focused only on literature published in scientific journals. This restricted synthesis of evidence from reports documented by governments and TB fighting NGOs within the region. Literature search was limited to studies published in English, preventing identification of studies published in French, Portuguese and Arabic which are official languages used by several SSA countries. Therefore, findings from these countries were not examined. Despite searching for literature using country names of sub-Saharan Africa, numerous countries within the region had no studies published on the subject. This limited the analysis to some regions within SSA and prompts cautious use of findings from this review. While none of the included studies received a weak rating on the EPHPP tool, most studies were of moderate quality because they were observational studies. This limits generalizability of findings from this systematic review and underpins the importance of further research on the effects of decentralization of MDR-TB care in various settings within sub-Saharan Africa.\u0026nbsp;\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, included studies have suggested that decentralizing MDR-TB services in SSA has increased access to MDR-TB services. More patients have been tested, diagnosed and enrolled into MDR-TB care in the region. Managing MDR-TB using decentralized models is also suggested to be less costly and more cost-effective than using centralized models. This is pertinent to SSA due to resource-constraints in many countries within the region. Also, through decentralizing MDR-TB services, countries in SSA are suggested to achieve and maintain high treatment success rates as well as retain more patients into care.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSub-Saharan African countries are, therefore, recommended to manage MDR-TB using more decentralized approaches than centralized approaches. Decentralized facilities should be well capacitated to ensure quality care is provided to MDR-TB patients. Efficient data recording systems should also be established at decentralized facilities as well as central facilities. This will enable effective monitoring and evaluation of various components of MDR-TB management such as patient treatment outcomes. More robust study designs such as randomized studies, e.g. stepped-wedge cluster randomized studies, are recommended as well as meta-analyses to estimate pooled estimates of treatment outcomes for the two treatment approaches in sub-Saharan Africa.\u0026nbsp;\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003ctable style=\"border: none;border-collapse:collapse;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 225.4pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003e\u003cstrong\u003eART\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 225.4pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003eAntiretroviral Therapy\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 225.4pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003e\u003cstrong\u003eDALY\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 225.4pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003eDisability Adjusted Life Years\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 225.4pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003e\u003cstrong\u003eDOT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 225.4pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003eDirect Observed Therapy\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 225.4pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003e\u003cstrong\u003eDR-TB\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 225.4pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003eDrug-resistant tuberculosis\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 225.4pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003e\u003cstrong\u003eDST\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 225.4pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003eDrug susceptibility testing\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 225.4pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003e\u003cstrong\u003eKZN\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 225.4pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003eKwaZulu Natal\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 225.4pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003e\u003cstrong\u003eLMIC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 225.4pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003eLow- and Middle-Income Countries\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 225.4pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003e\u003cstrong\u003eLTFU\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 225.4pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003eLost to follow up\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 225.4pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003e\u003cstrong\u003eMDR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 225.4pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003eMultidrug-resistance\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 225.4pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003e\u003cstrong\u003eMDR-TB\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 225.4pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003eMultidrug-resistant tuberculosis\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 225.4pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003e\u003cstrong\u003eNGO\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 225.4pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003eNon-Governmental Organization\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 225.4pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003e\u003cstrong\u003eRR-TB\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 225.4pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003eRifampicin-resistant tuberculosis\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 225.4pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003e\u003cstrong\u003eSSA\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 225.4pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003eSub-Saharan Africa\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 225.4pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003e\u003cstrong\u003eWHO\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 225.4pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003eWorld Health Organization\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 225.4pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003e\u003cstrong\u003eXDR-TB\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 225.4pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003eExtensive drug-resistant tuberculosis\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eApproval to conduct this study was granted by the University of Witwatersrand ethics committee (Medical), reference number, W\u0026ndash;CBP\u0026ndash;210219-01. A copy of the waiver from ethics certificate is attached as additional file.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analysed during this study are included in this published article [and its supplementary information files].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe research project was supported by a postgraduate training Scholarship from the\u0026nbsp;TDR, the UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases - hosted at the World Health Organization in Geneva, Switzerland. TDR grant number: B40299. First author ORCID ID:\u0026nbsp;0000-0001-6298-3549\u003c/p\u003e\n\u003cp\u003eTDR played no role in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor\u0026rsquo;s contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMA designed the study, searched for published studies in databases, selected the studies for inclusion, assessed the quality of included studies, extracted, analysed and interpreted the data from studies, and was a major contributor in writing the manuscript.\u003c/p\u003e\n\u003cp\u003eYL participated in study selection, quality assessment of included studies, re-checking information extracted from studies, reading and reviewing the manuscript.\u003c/p\u003e\n\u003cp\u003eSM participated in the design of the study as well as reading and reviewing the manuscript.\u003c/p\u003e\n\u003cp\u003eLI participated in the design of the study as well as reading and reviewing the manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank Godwin Kalu for proofreading the manuscript.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003cp\u003e1. \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Barberis I, Bragazzi NL, Galluzzo L, Martini M. 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Emerg Infect Dis. 2008;14(5):701\u0026ndash;8.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e47. \u0026nbsp; \u0026nbsp; \u0026nbsp;Fitzpatrick C, Floyd K. A Systematic Review of the Cost and Cost Effectiveness of Treatment for Multidrug-Resistant Tuberculosis. Pharmacoeconomics [Internet]. 2012;30(1):63\u0026ndash;80. Available from: https://doi.org/10.2165/11595340-000000000-00000\u003c/p\u003e\n\u003cp\u003e48. \u0026nbsp; \u0026nbsp; \u0026nbsp;Morris L, Hiasihri S, Chan G, Honjepari A, Tugo O, Taune M, et al. The emergency response to multidrug-resistant tuberculosis in Daru, Western Province, Papua New Guinea, 2014-2017. Public Heal Action [Internet]. 2019 Sep 21;9(Suppl 1):S4\u0026ndash;11. Available from: http://dx.doi.org/10.5588/pha.18.0074\u003c/p\u003e\n\u003cp\u003e49. \u0026nbsp; \u0026nbsp; \u0026nbsp;Mitnick C, Bayona J, Palacios E, Shin S, Furin J, Alc\u0026aacute;ntara F, et al. Community-Based Therapy for Multidrug-Resistant Tuberculosis in Lima, Peru. N Engl J Med. 2003;348(2):119\u0026ndash;28.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e50. \u0026nbsp; \u0026nbsp; \u0026nbsp; Sam S, Shapiro AE, Sok T, Khann S, So R, Khem S, et al. Initiation, scale-up and outcomes of the Cambodian National MDR-TB programme \u0026nbsp;2006-2016: hospital and community-based treatment through an NGO-NTP partnership. BMJ open Respir Res. 2018;5(1):e000256.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Multidrug-resistant tuberculosis, Centralized MDR-TB care, Decentralized MDR-TB care, Access to MDR-TB services ","lastPublishedDoi":"10.21203/rs.3.rs-2077078/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2077078/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMultidrug-resistant tuberculosis (MDR-TB), which is resistant to rifampicin and isoniazid, is a significant public health concern. MDR-TB care has transitioned from being centralized where inpatient care provided at specialized facilities to being decentralized, where the focus is on outpatient care provided at the community. This review aims to synthesize results of studies on the effect of decentralizing MDR- TB care on the accessibility of services and patient treatment outcomes in sub- Saharan Africa (SSA).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA systematic review which synthesized observational studies, interrupted time series and cost analyses from SSA, published between 2011 and 2021 was conducted. Five databases (PubMed, Cochrane library, Global health, Scopus and Global Index Medicus (WHO)) were searched to identify eligible studies. Quality assessment of included studies was conducted using the Effective Public Health Practice Project (EPHPP) tool for observational studies and the CHEERS checklist for cost evaluation studies.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTwelve studies met the eligibility criteria for inclusion. In SSA, decentralization of MDR-TB care has been suggested to improve utilization and cost of MDR-TB services. The treatment cost has reduced and volume of patients utilizing both diagnostic and treatment services has increased in all countries represented by the studies. Increased successful treatment as well as reduction in patients who are lost to follow up have also been suggested to be outcomes of decentralizing MDR-TB treatment services within SSA.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn resource limited settings such as those in SSA, studies have suggested that decentralizing MDR-TB services is beneficial as it enables increased utilization of diagnostic and treatment services at lower service delivery costs. High retention into care and treatment success rates are also suggested to be better achieved and maintained when using decentralized approaches than centralized approaches.\u003c/p\u003e","manuscriptTitle":"The Effect of Decentralized Services on Multidrug-Resistant Tuberculosis Care in Sub- Saharan Africa: A Systematic Review","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-09-23 18:40:21","doi":"10.21203/rs.3.rs-2077078/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"4ef6d514-efca-442b-87ed-aaedd8c43820","owner":[],"postedDate":"September 23rd, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2022-11-02T07:59:28+00:00","versionOfRecord":[],"versionCreatedAt":"2022-09-23 18:40:21","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-2077078","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2077078","identity":"rs-2077078","version":["v1"]},"buildId":"rHA-KDH7Qsr4HCuvH75dn","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}