Cost-Benefit Analysis of Pre-Entry Tuberculosis Screening Policy: Nepalese and Japanese Perspectives

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Methods: This study used data from the Nepal Demographic and Health Survey; and from Japan’s Legal Affairs Bureau and Tuberculosis Surveillance Center. We used cost-benefit analysis to examine the effect of the pre-entry TB screening policy. Total cost, total benefit and net benefit for both countries were compared for the policy scenarios “With” and “Without”, using net present value (NPV). In order to address parameter difference for uncertainty, we conducted sensitivity analysis using Monte Carlo simulation with secondary transmission rate. Results: Between 2014 and 2018 in Japan, NPV of Nepalese student increased from USD 1.9 million to USD 2.9 million; likewise, NPV of Nepalese workers grew from USD 1.1 million to USD 3.0 million. The increase in NPV was greater than zero, meaning that the implementation of the policy could produce a benefit for Japan regarding prevention of increase in number of new TB cases. In Nepal, the predicted number of foreign migrant applicants with newly diagnosed TB increased. Total NPV for Nepal was negative since total cost was greater than the benefit, suggesting added burden of direct TB cost. Conclusions: Implementation of pre-entry TB screening policy for foreign migrants arriving in Japan from Nepal with high TB burden would achieve efficient cost-saving through reduction of number of newly diagnosed TB cases including those with transmission risk. Figures Figure 1 Figure 2 Figure 3 Highlights Policy Implementation of pre-entry TB screening in Japan was assessed by social value using cost benefit analysis on both Nepalese and Japanese perspectives. The policy effectiveness was calculated the risks of TB incidence related to cost and benefit with transmission risks. The policy evaluation suggests that pre-entry TB screening would have prevented increase in number of new TB cases in Japan, and would in turn have reduced TB healthcare costs and productivity loss. 1. Introduction Respiratory infections are now a major health concern worldwide with the most serious recent lung infection coronavirus disease (COVID-19), declared by the World Health Organization (WHO) a public health emergency of international concern (PHEIC) in January 2020 [ 1 ]. Equally threatening, tuberculosis (TB), a respiratory tract infection [ 2 ], was declared a global health emergency in 1993 [ 3 ]. Up to 2019, TB remains the world’s biggest infectious killer, taking more than 1.5 million lives in 2018 [ 4 ]. Despite efforts to eliminate TB, countries with low incidence of TB experience high concentrations of cases in at-risk groups as a result of cross-border migration related to globalization [ 5 ]. High-income countries are now concerned about TB morbidity and mortality, mainly the result of the arrival of individuals born in low income countries with high TB burden [ 6 ]. The WHO TB framework End TB by 2035 has identified migration by individuals infected with TB as a priority target for action in low incidence countries [ 7 ]. In the past few decades, Japan has been receiving increased numbers of migrants, including visitors, students, and workers from overseas. In 2019, the total number of migrant workers from Nepal in Japan was 91,770, making Nepalese third largest migrant group an increase of 12.5% over the previous year [ 8 ]. In 2019, Nepal was designated the first country to sign an agreement with Japan for specific-skilled migrant workers, aimed at greater transparency under Japan’s immigration control and refugee recognition act [ 9 ]. Although good connections and friendship have been established through development projects for health, education, and tourism between Nepal and Japan [ 10 ], the number of migrant workers with TB has increased steadily in recent years [ 11 ]. In 2018, 1,667 foreign-born migrants with TB were reported in Japan, accounting for 10.2% of Nepalese migrant cases [ 12 ]. In fact, the yearly increase in number of Nepalese TB cases could increase the number of newly identified TB cases in the native Japanese population [ 13 ]. Studies indicate that to reduce the number of active TB cases among incoming migrants a pre-entry TB screening program is essential [ 14 ]. However, Japan has not implemented a mandatory pre-entry TB screening policy for applicant migrants as part of its visa application process, because a pre-entry screening requirement for all migrants would inflict an economic burden on migrants and their home countries, and could even damage the general population's health due to exposure. Nevertheless, due to the seriousness of the issue of migrants with TB, the Japanese government finally decided to introduce a TB pre-entry screening requirement for middle- to long-term applicants from countries with a high number of TB cases (China, Indonesia, Myanmar, Nepal, the Philippines, and Vietnam), effective 2020 [ 15 ]. However, that action is insufficient in light of the estimated economic impact of the pre-entry TB screening policy on social cost. This study examined the expected cost and benefit of pre-entry TB screening policy on both Japan and Nepal for the period 2014–2018. The aim of that assessment is to support confidence-building and achieve mutual value for the partner countries. 2. Method 2.1 Policy scenarios for analysis Due to the increased number of TB patients in Japan from high-risk TB incidence countries, Japanese government policy requires pre-entry TB screening to identify migrants with TB [ 15 ]. TB screening for migrants is implemented as a mandatory part of the visa application procedure targeting five high-burden TB incidence countries, including Nepal [ 16 ]. In Fig. 1, the left flow presents the with policy implementation scenario, where visa applicants should undergo TB screening in their country of origin. TB screening includes a general health check-up (health background check, physical examination, and chest radiography (CXR)), in line with the Japanese Pre-entry TB Screening (JPETS) procedure [ 17 ]. Mycobacterium tuberculosis analysis of three sputum smears and a culture examination are required if the results of the general health check-up suggest active TB. TB diagnosed applicants are not allowed entry into Japan until completion of TB treatment in line with WHO treatment guidelines, as well as the national TB protocol. Applicants are required to provide including appropriate certification that they are free of TB. The right flow in Fig. 1 presents the current without policy implementation scenario, where clinical TB screening of migrants is conducted within Japan. If the migrants present initial TB symptoms, they take a basic TB clinical examination as part of a general health check-up at clinic or hospital which ensure whether the patient has a suspected TB infection. The migrants must take a Mycobacterium tuberculosis examination of three sputum smears if TB infected. If the sputum test or Polymerase Chain Reaction (PCR) perform positive and the migrants is diagnosed with TB, the physician sends the resident to a TB-specific medical facility or hospital for TB treatment to completion as specified in Japan’s TB treatment protocol. 2.2 Analytical framework The expected impacts of pre-entry TB screening policy were assessed using cost-benefit analysis approach. The analytical period was set within one year of each of 2014 to 2018, when the pre-entry TB screening policy still had not been introduced. In this CBA, total cost, total benefit and net benefit for Japan and Nepal were measured and these values for “ with pre-screening policy ” scenario and “ without pre-screening policy ” scenario are compared. Cost is measured as the fees for TB screening testing of migrants and TB treatment of patients with TB. Benefit is measured as the avoidance of productivity loss of foreign migrants with TB through by means of incidence risk reduction. Sensitivity analysis is conducted by Monte Carlo simulation. From Japan’s perspective, costs are covered by Universal Health Coverage (UHC), which provides effective coverage performance for improving health outcomes and reducing patients cost via equitable health services for all [ 18 ] [ 19 ]. Japan publicly funded TB healthcare enables patients with independent residency and national health insurance status to access healthcare services, and the cost of TB-related healthcare services is fully subsidized [ 20 ] [ 21 ]. On the other hand, in Nepal, individuals have to pay the full cost of health services because of insufficient coverage UHC, with some exceptions [ 22 ]. 2.3 Estimation of active TB population The target population of this study is foreign-born migrants who plan to acquire Foreign Resident status by first applying for a visa for middle- to long-term duration of stay in Japan [ 9 ]. The foreign residents with TB include those with permanent, study abroad, technical intern, migrant, accompanying family, Japanese spouse, and others Japanese residence status [ 12 ]. Data on foreign residents to Japan and on TB cases in Japan were collected from the Legal Affairs Bureau Japan and the Tuberculosis Surveillance Center Japan, respectively. TB Incidence data of Nepal are sourced from Nepal Demographic and Health Survey and Annual Report by Nepal’s Department of Health Service (DHS) [ 23 ]. The cumulative incidence of TB as an annual figure was calculated by dividing the total population by the number of TB patients predicted under policy implementation during the study period. For estimation of the active TB population in Japan under the policy of pre-entry TB pre-screening diagnostic tests, the screening test sensitivity rate is a key prediction value. TB diagnosis depends on the result of sputum smear microscopy test, which can detect either smear-positive or non-infectious [ 24 ]. We estimate the predicted active TB population with the test sensitivity rate. Kurumi et al. [ 25 ] found the sensitivity of sputum smear microscopy test in Nepal to be 62% in 2016. The sputum smear microscopy test is low cost and easy to perform, even in developing countries, while only a few PCR screening methods have been made available in Nepal’s health facilities since 2015 [ 26 ]. On the other hand, the sensitivity of smear microscopy performance in Japan is around 72% [ 27 ] while the positive predicted value (PPV) of PCR is over 95% [ 28 ]. Thus, we adopted PCR as the test for Japan. Detailed statistical formula is described in supplementary Method 1–1. 2.3.1 Present Condition In our calculations of the population under the without-policy scenario (i.e. testing conducted in Japan) we used number incidence of TB based on data provided by the Tuberculous Research Institute. In the Japan with-policy scenario, total possible active TB population equals the number of TB false-negative cases in screening tests in Nepal. The difference in predicted active TB cases between with-policy and without-policy can be estimated as the number of active TB cases prevented by implementation of the policy. Likewise, under the with-policy scenario (i.e. testing conducted in Nepal), 62% of TB patients in Nepal had a positive sensitivity test result and were denied entry to Japan, and 38% of the TB population were false negatives and were allowed entry to Japan. Our analysis predicts the total possible active TB population in Japan without policy by dividing the number of total TB cases detected in the screening tests by the sensitivity test rate to estimate the number of TB patients in the active TB population (including false negatives). From the Japanese perspective, the size of the active TB population is calculated as (Nepalese resident in Japan/ Sensitivity test rate) × transmission rate [150%] in the without-policy scenario; and (Nepalese resident in Japan × incidence rate in Nepal) ⁄ Sensitivity test rate [62%]-TB population × Incidence rate in Nepal) × transmission rate [150%] in the with-policy scenario. From the Nepalese perspective, there have been active Nepalese TB cases in Japan, and thus no direct benefit for Nepal in the without-policy scenario; the size of active TB population is calculated as (Nepalese resident in Japan × incidence rate in Nepal / Sensitivity test rate [62%]-False negative cases) × transmission rate in With-policy scenario. 2.4 Expected impact on the cost and benefit The expected impact of the different hypothetical policy scenarios can be measured by comparing cost and benefit of “with policy” and “without policy” for both Japan and Nepal (Fig. 2). There are two national perspectives, with-policy and without-policy. Thus, we have a prediction of the outcomes of the two scenarios, in terms of cost, benefit, and net benefit (benefit minus cost) monetized in local currency with consideration of inflation rate. 2.4.1 Cost of TB screening test The full cost is presented as local prices in US dollars with inflation and the exchange rate of each year, according to Financial Statistics of the International Monetary Fund (IMF) [ 29 ]. All costs were reported within each year from 2014 to 2018 as total social cost from each national perspective. The data for Japanese local cost including cost of TB screening and treatment is taken from National Database (NDB) [ 30 ]. TB test prices in Nepal are drawn from the guidance for TB testing by UK [ 31 ], and treatment cost is quoted from Gurung et al. [ 32 ]. Costs of TB testing and treatment reflect the different approaches to screening and treatment under WHO guidelines for treatment criteria and National TB methodology. The screening cost consists of general health check-up, examination of three sputum smears, PCR, chest radiography, and standardized basic clinical TB examination. Indirect costs of transportation, caregiver or health worker time, etc. are not within the scope of our analysis [ 33 ]. 2.4.2 Cost of TB treatment The cost of the TB treatment drug regimen is calculated as the total number of tablets required for six months’ treatment with the first-line drugs specified in both the WHO guideline and national TB methodology. The first-line drugs include Rifampicin (RFP), Pyrazinamide (PZA), Isoniazid (INH), and Rifabutin (RBT), as per the 2018 Japanese TB treatment guideline [ 34 ]. We calculated the cost of these drugs taken three times a day for six months; pre-treatment phase to the intensive period as the TB treatment in Nepal [ 32 ]. 2.4.3 The benefit by avoidance of productivity loss Cost of TB treatment includes medical cost and time loss resulting from undertaking TB treatment for a minimum of six months. The treatment requires that the patient be isolated, which would reduce the patient’s income [ 35 ]. In that light, the assumption of benefit considers the avoidance of productivity loss by both patient and nation through incidence risk reduction via policy implementation. We estimate wages in Japan using sectoral data from the Ministry of Health, Labour, and Welfare in Japan [ 36 ], and in Nepal using monthly GNI per capita obtained from IMF [ 37 ] (constant LCU: local currency unit for one year). Estimation of income of student dependents of foreign residents is based on that projected wage. Our primary estimation of the net present value (NPV) of implementation of the policy equals the difference between the present value of the social benefit (PVsb) and the present value of social cost (PVsc). From the Japanese perspective, NPV = 0-Total implement fee།Total productivity loss; while form the Nepalese perspective, NPV = 0།Incremental test fee།Total treatment fee།Total productivity loss. In that light, we need to estimate the impact of implementation of policy as an incremental net social benefit (NSB) = Net benefit in With-policy scenario །Net benefit in Without-policy scenario. We provide the statistical formula in more detail in supplementary Method 1–2. 2.5 Sensitivity analysis The NPV is likely uncertain due to changes in the value of key input parameters, uncontrollable factors of epidemics, such as the chance of infecting other people could affect the benefit and cost that would be anticipated by the proposed policy. In Monte Carlo simulation of TB transmission impact, the probability of distribution in the population is a key input parameter for all essential uncertain quantitative estimations. For instance, the interval of sensitivity analysis in Cyprus presented 0–10% and 10–25% [ 14 ]. Given the fact of large economic impacts such as inflation, deflation and unemployment rate in Nepal and Japan, WHO key facts suggest that people carrying TB bacteria have a 5–15% chance of falling ill with TB [ 38 ]. We thus calibrate the parameters of increase and/or decrease of the incidence of TB probability over the intervals 0–15 and 15–30%. 2.6 Conceptualization toward burden sharing The With-policy scenario requires Nepal to take on the additional costs of TB screening test of migrants to Japan. In high burden TB countries, out-of-pocket (OOP) expenditures have accounted for at least 45% of total health expenditures [ 39 ], and more than 50% in Nepal [ 40 ] due the absence of UHC [ 41 ]. They are suffering increased health-related financial difficulties in terms of OOP expenditure and access to healthcare. The catastrophic cost of healthcare (i.e. TB detection, care and treatment) in high TB burden countries called for affordable TB-specific interventions and sustainable mechanisms for financing those interventions, as well as progress under UHC [ 42 ]. Thus, it would be more equitable to develop a methodology of burden sharing so as to consider the net benefit of Japan and Nepal in calculations of appropriate share of investment transfer, so as to maximize Nepal’s incentive to develop public health infrastructure for TB screening tests, care and treatment for disease prevention and control. 3. Results The predicted numbers of active TB cases and NSB for workers/students (2014 to 2018) in Japan and Nepal are shown in Table 1. For Japan, the predicted number of active TB cases increased for both with- and without-policy. Still, the percentage of active TB cases among students is higher than that among workers. Significantly, the outcome of fewer cases of active TB in the With-policy case constitutes reduction of active TB incidence risk. In addition, increased worker NPV under the TB screening policy in 2014 was estimated at JPY 118.4 million (USD 1.1 million) and increased to JPY 332.1 million (USD 3.0 million) in 2018. In turn, the result of the increase of student NPV was a positive, JPY 203.4 million (USD 1.9 million) in 2014, and grew substantially to JPY 320.9 million (USD 2.9 million) in 2018. The increase in NPV was greater than zero, which implies that the implementation of the TB screening policy in Japanese society could produce a significant benefit in terms of prevention of increased number of cases of active TB. For Nepal, the predicted number of Nepalese with active TB increased, with student incidence greater than that for workers. Student NPV decreased from -NPR 384.4 million (USD − 3.9 million) in 2014 to -NPR 887.0 million (USD-8.1 million) in 2018, where pre-entry TB screening policy was implemented. Total NPV for Nepal was negative due to the total cost being higher than the benefit (productivity loss), which indicates the imposition of the burden of direct cost, including testing and treatment costs, on Nepalese society. We applied 0–15 and 15–30% sensitivity analysis in a Monte Carlo simulation as the secondary transmission rate on incremental NPV for both perspectives in order to address parameter difference uncertainty. The NPV for Japan increased depending on the TB incidence rate in each interval on the transmission scale. When a high 15% increase in TB transmission rate might indicate a high risk of becoming infected, the output would increase student NPV from JPY219.0 million (USD 2.1 million) to JPY345.4 million (USD 3.1 million) for 2018 (Table 2). In contrast, the negative value of NPV distribution among Nepalese students increased to minus 1 billion NPR (USD 8.7 million) in 2018 (Table 3)—very costly when the risk of transmission rates increased by more than 30%. We provide Fig. 1 in more detail in Supplementary Result 2 − 1 and Fig. 2 in Supplementary Result 2–2. The scenario results show that the implementation of pre-entry TB screening for applicants for Japanese visas could involve significant cost for Nepal (Fig. 3). We provide Table 1 in more detail in supplementary Result 2–3. As shown above, Nepal bears a much heavier burden than Japan. Significantly, the difference in NPV is counterbalanced by the burden of cost allocation, which is accentuated by the huge economic gap between two countries. Level of fiscal burden should be taken into consideration under a fair sharing mechanism between collaborating countries. Although, methods for determining burden-sharing rate for global health aid projects have not yet been developed, our net benefit scenario results could be considered as a net benefit contributing to health equality. 4. Discussion 4.1 Policy implications Assessment of Nepal's and Japan's expected costs and benefits of resulting from Japan’s pre-entry TB screening policy implementation for prospective Nepalese residents of Japan should be conducted with consideration of social value in terms of monetization. Our multi-dimensional evaluation simulates empirically scenarios reflecting both perspectives, so as to examine the potential outcome of implementation of the new policy design in Japan. Specifically, our approach measures the social values of pre-entry TB screening strategy. The simulation suggests that pre-entry TB screening would have prevented about 181 active TB cases in Japan for 2018, and would in turn have reduced TB screening costs and worker productivity loss—welcome outcomes from the Japanese perspective. This encores that the appropriate pre-entry TB screening policy for that group has been discussed [ 43 ], would contribute to the prevention, and eventually elimination, of TB in Japan. Overseas LTBI screening and treatment for refugees and foreign-born residents in the US could serve as a model for the reduction of active TB by domestic health prevention management [ 44 ]. Current TB cross-border management issues are inadequate for TB incidence risk reduction, infection control, collaboration, and the sharing of global data [ 45 ]. The reduction of risk of TB incidence is recommended as a policy-based practice within public health emergency management at every level. National health prevention and disease control could serve as health emergency management instruments in neighboring countries vis -à- vis trans-border migration. Due to weak public and global health emergency management and the increasing number of foreign residents with TB worldwide, cross-border infectious disease transmission is now a major human security concern, even threatening international peace and security [ 46 ]. Human security is now recognized in Japan as a central concern; Japan must promote social resilience through international health cooperation [ 47 ]. Our scenario results estimate that pre-entry TB screening testing within Nepal could have been identified 137 TB cases among 42,346 visa applicants from Nepal in 2018; those individuals could have undergone TB treatment in Nepal until issued TB-free certificates. Although pre-entry TB screening strategy could contribute to the establishment of aggressive TB screening and treatment in Nepal, it could have a negative impact on TB-related expenditure for households with insufficient healthcare coverage [ 48 ]. WHO's End of TB strategy identified reduction of TB-affected household expenditures as a priority means of preventing catastrophic economic costs of TB in low income countries [ 49 ]. The implementation of TB screening pre-entry to Japan would reduce TB incidence risk, and early TB diagnosis prior to entry to Japan would ensure elimination of a substantial proportion of detected TB cases. In Japan, there remains little evidence of sufficient awareness within the target population (Nepal) of TB control, prevention and treatment. The target population diagnosed with TB could be subjected to considerable disease-related burden, including loss of income, discretionary time for TB care, and treatment cost difficulties related to lack of health coverage. Fair sharing of net benefits as public goods is likely to improve health equity, assuming cooperation by developing countries [ 50 ]. According to some empirical studies, the burden-sharing required to achieve the global health target will call for large efforts by multi-stakeholders [ 51 ]. The outbreak of the Covid-19 global pandemic has confirmed that policy implementation reflecting migrant home and destination is indispensable for a resilient public health system and infrastructure for financing holistic health diplomacy development [ 52 ]. 4.2 Limitations and future perspective TB has been designated an infectious disease by law in Japan, with provision of full coverage of treatment costs. In the absence of such system for Nepal, measures of willingness to pay and shadow price to estimate the value of a statistical life (VSL) are not applied in this study. Nevertheless, this study clarifies the relationship between economic impact and Japanese pre-entry TB screening policy aimed at the elimination of TB. The empirical estimates elucidate the spillover effect from health system reinforcement through international collaboration, while technology application is expected to enhance the interpretation of the change from the value chain in the both countries. Regarding the public health impact of infectious disease exacerbated by cross-border issues, implementation of the policy would enhance the effect of TB incidence risk reduction and cost-saving by foreign born residents of Japan. Migrant nations subject to the implementation of the policy, especially low-income countries, would bear the cost of TB testing and treatment. Hence, establishing a burden-sharing mechanism would generate a spillover effect on population health and reduce vulnerability to financing shock for the migrant county, in turn deepening the interdependence between Nepal and Japan in terms of inclusive development for the elimination of TB. 5. Conclusions This study estimated the expected policy implementation costs and benefits of pre-entry TB screening testing and treatment targeting Nepalese born residents of Japan, a high TB burden country. In order to give consideration to the different perspectives on the policy implementation scenarios, we calculated the risks of TB incidence related to cost and benefit with transmission risks, as measures of policy effectiveness in each country. We reason that effective TB infection control could help reduce the output value of productivity loss, which would in turn lead to cost-saving the implementation of pre-entry TB screening policy in Japan. By identifying an optimal combination of expected cost and benefit, it possible to give stakeholders various options for TB countermeasures both nationally and internationally. Policy makers understand that it is vital to provide information and guidance regarding the recognized impacts, considering different perspectives, of this policy setting process. It should be noted that the simulation framework could also be applied to the design of Covid-19 countermeasures. Declarations Acknowledgements: We sincerely express our gratitude to the former Director General of the Bureau of International Health Cooperation at the National Center for Global Health and Medicine (NCGM), Japan, for his invaluable support and guidance throughout this research. Funding Statement : This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Consent to Publish declaration: Not applicable. Ethics and Consent to Participate declarations: Not applicable. Ethical and conflict of interest statement We used secondary health data from the Nepal Demographic and Health Survey and the Nepal Department of Health Services (DHS) Annual Report [23]; and from Japan’s Legal Affairs Bureau and Tuberculosis Surveillance Center. It is not possible to identify individual health information of participants from the data, so this study did not require ethical approval or conflict of interest statements. References World Health Organization. Statement on the second meeting of the International Health Regulations (2005) Emergency Committee regarding the outbreak of novel coronavirus (2019-nCoV)’. Newsroom detail, 30 January 2020. Available from https://www.who.int/news-room/detail/30-01-2020-statement-on-the-second-meeting-of-the-international-health-regulations-(2005)-emergency-committee-regarding-the-outbreak-of-novel-coronavirus-(2019-ncov). [Accessed January 28 2021]. 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Available from: https://www.who.int/news-room/fact-sheets/detail/tuberculosis. [Accessed January 28 2021]. WHO 2017, Global Tuberculosis Report 2017, Available from: https://www.who.int/tb/publications/global_report/gtbr2017_main_text.pdf?ua=1. [Accessed January 28 2021]. Mahato P, Paudel G. Access to free health-care services for the poor in tertiary hospitals of western Nepal: a descriptive study. WHO South East Asia J Public Health. 2015;4(2):167-175. Swe K, Rahman M, Rahman M, Saito E, Abe S, Gilmour S, Shibuya K. Cost and economic burden of illness over 15 years in Nepal: A comparative analysis. PLoS ONE 2018;13(4): e0194564. Floyd K, Glaziou P, Zumla A, Raviglione M. The global tuberculosis epidemic and progress in care, prevention, and research: an overview in year 3 of the End TB era. Lancet Respir Med 2018;6(4):299-314. Kawatsu L, Uchimura K, Ohkado A, Kato S. Pulmonary tuberculosis and non-recent immigrants in Japan - some issues for post-entry interventions. Western Pacific surveillance and response journal: WPSAR. 2017; 8 (4),13-19. Wingate L, Coleman M, de la Motte C, Semple M, Zhou W, Cetron M, Painter J. 2015, A cost-benefit analysis of a proposed overseas refugee latent tuberculosis infection screening and treatment program. BMC Public Health. 2015;15:1201-1215. Dara M, Sulis G, Centis R, D’Ambrosio L, de Veries G, Douglas P, Garcia D, Jansen N, Zuroweste E, Migliori GB. Cross-border collaboration for improved tuberculosis prevention and care: policies, tools and experiences. The International Journal of Tuberculosis and Lung Disease : the Official Journal of the International Union Against Tuberculosis and Lung Disease. 2017;21(7):727-736. United Nations 1945, Charter of the United Nations. Available from: https://www.un.org/en/sections/un-charter/introductory-note/index.html. [Accessed January 28 2021]. Nomura S, Sakamot H, Sugai M, Nakamura H, Sakurai K, Lee S, Ishizuka A, Shibuya K. Tracking Japan’s development assistance for health, 2012–2016. BMC Global Health 2020;16, 32 (2020). . Dixit K, Rai B, Prasad T, Mishra G, de Siqueira-Filha N, Paudel P, Levy J, Rest J, Gurung S, Djotal R, Biermann O, Vinet K, Lonnroth K, Squire S, Caws M, Wingfield T. Research protocol for a mixed-methods study to characterise and address the socioeconomic impact of accessing TB diagnosis and care in Nepal [version 2; peer review: 2 approved with reservations]. Wellcome Open Res 2020; 5 :19. WHO 2015. Global Tuberculosis report 2015. Global strategy and targets for tuberculosis prevention, care and control after 2015 a , The official text approved by sixty seventh World Health Assembly, 14 March 2014. Available from: https://www.who.int/tb/strategy/End_TB_Strategy.pdf?ua=1. [Accessed January 28 2021]. Kaul I, Faust M. Global public goods and health: taking the agenda forward, Bulletin of the World Health Organization 2001;79:869-874. Shekar M, Kakietek J, D'Alimonte M, Rogers H, Eberwein J, Akuoku J, Pereira A, Soe-Lin S, Hecht R. Reaching the global target to reduce stunting: an investment framework, Health Policy Plan 2017;32(5):657-668. Shimizu K, Kondo T, Tokuda Y, Shibuya K. An open letter to Japan’s new Prime Minister. Lancet, 2020; 396:e57. Tables Tables 1 to 3 are available in the Supplementary Files section Additional Declarations No competing interests reported. Supplementary Files CBATables.xlsx 20210209TBCBAAppendices.docx 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. 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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-5766264","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":399954266,"identity":"e6ec740a-3811-47f1-bf45-bbeed15702b7","order_by":0,"name":"Yoko Iwaki","email":"","orcid":"","institution":"Osaka International Cancer Institute","correspondingAuthor":false,"prefix":"","firstName":"Yoko","middleName":"","lastName":"Iwaki","suffix":""},{"id":399954268,"identity":"1008d71f-74d6-4ba6-b14f-441fa3af30ed","order_by":1,"name":"Takayuki Hayashi","email":"","orcid":"","institution":"National Graduate Institute for Policy Studies","correspondingAuthor":false,"prefix":"","firstName":"Takayuki","middleName":"","lastName":"Hayashi","suffix":""},{"id":399954270,"identity":"635467f3-4c95-4a59-98dc-8a873030978f","order_by":2,"name":"Shuhei Nomura","email":"","orcid":"","institution":"Keio University Global Research Institute","correspondingAuthor":false,"prefix":"","firstName":"Shuhei","middleName":"","lastName":"Nomura","suffix":""},{"id":399954271,"identity":"84f2dd81-74cd-4153-aeff-59259c9cb67c","order_by":3,"name":"Shoko Shimamura","email":"","orcid":"","institution":"Juntendo University","correspondingAuthor":false,"prefix":"","firstName":"Shoko","middleName":"","lastName":"Shimamura","suffix":""},{"id":399954272,"identity":"b9437985-19ee-4bf7-9d82-33b0f16ecba4","order_by":4,"name":"Rohita Gauchan","email":"","orcid":"","institution":"Trithunga Tours and Travels","correspondingAuthor":false,"prefix":"","firstName":"Rohita","middleName":"","lastName":"Gauchan","suffix":""},{"id":399954273,"identity":"cec7589b-fec3-4357-afbe-de720c6e2ee3","order_by":5,"name":"Michael C. Huang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/UlEQVRIiWNgGAWjYDACZgY2IGnBYADmVTAwsDeAGDwEtUhAtZwBKj5ASAsDshbGNpgWPEC3nfnZgx8VEgzmEsnPHn6dV5fHw8B87AODzB2cWswOs5kb9pyRYLCckWZuLLvtcDEPA1vyDAaeZ3i08LBJ8LZJ1G+4kWAmLbntQOJ+Bh5joPMO49Ui+fcf0C830r9JS86pS+whRos0bwNIS46Z5McGZmK0sJlJyxwDajnzpkya4RjQL8xsyQwJ+Pxy/vAzyTc1NgwGx9O3Sf6oAYYYe/Nhho89uEMMBTADIzABGLkMDIk9B4jTwvgDpAUMfhCpZRSMglEwCkYCAADvP0vV7W8tQwAAAABJRU5ErkJggg==","orcid":"","institution":"Ocean Policy Research Institute (OPRI) of the Sasakawa Peace Foundation","correspondingAuthor":true,"prefix":"","firstName":"Michael","middleName":"C.","lastName":"Huang","suffix":""}],"badges":[],"createdAt":"2025-01-05 06:08:07","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5766264/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5766264/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":73702377,"identity":"81b97676-4f91-4d1d-b8e9-8ef00d77b4ec","added_by":"auto","created_at":"2025-01-13 17:33:52","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":395319,"visible":true,"origin":"","legend":"\u003cp\u003ePolicy scenario: TB screening procedure in Nepal and Japan\u003c/p\u003e","description":"","filename":"CBAFigure1.png","url":"https://assets-eu.researchsquare.com/files/rs-5766264/v1/98627e9acbf85167a8008b84.png"},{"id":73702384,"identity":"7c1bff81-8c7b-4dff-893b-afdc17dfd7fe","added_by":"auto","created_at":"2025-01-13 17:33:53","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":203348,"visible":true,"origin":"","legend":"\u003cp\u003ePolicy scenario: Policy simulation algorithm\u003c/p\u003e","description":"","filename":"CBAFigure2.png","url":"https://assets-eu.researchsquare.com/files/rs-5766264/v1/8269c9c85884c4c59b2f34e7.png"},{"id":73702387,"identity":"6b833f3e-83f5-44bd-a421-0a29e7e390e4","added_by":"auto","created_at":"2025-01-13 17:33:53","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":66486,"visible":true,"origin":"","legend":"\u003cp\u003eNet present value for Nepalese workers and students in Nepal and Japan\u003c/p\u003e","description":"","filename":"CBAFigure3.png","url":"https://assets-eu.researchsquare.com/files/rs-5766264/v1/1ae07ec3fc371eb4dbe43881.png"},{"id":74254427,"identity":"5190a7f6-a358-478c-8452-32559789acfd","added_by":"auto","created_at":"2025-01-20 11:08:44","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1241693,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5766264/v1/c549c30f-272d-4f4b-bfe7-0033ba0ea563.pdf"},{"id":73703613,"identity":"b584c29e-1ad4-4cbe-ae73-6413b77289cc","added_by":"auto","created_at":"2025-01-13 17:41:53","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":17476,"visible":true,"origin":"","legend":"","description":"","filename":"CBATables.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-5766264/v1/a7d0192f2e670fc2c57d003c.xlsx"},{"id":73702379,"identity":"e7c2ca15-68f9-471f-be7c-cd8ebf105e95","added_by":"auto","created_at":"2025-01-13 17:33:53","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":102872,"visible":true,"origin":"","legend":"","description":"","filename":"20210209TBCBAAppendices.docx","url":"https://assets-eu.researchsquare.com/files/rs-5766264/v1/5762c797d650816427dcaf38.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Cost-Benefit Analysis of Pre-Entry Tuberculosis Screening Policy: Nepalese and Japanese Perspectives","fulltext":[{"header":"Highlights","content":"\u003cul\u003e\n \u003cli\u003ePolicy Implementation of pre-entry TB screening in Japan was assessed by social value using cost benefit analysis on both Nepalese and Japanese perspectives.\u003c/li\u003e\n \u003cli\u003eThe policy effectiveness was calculated the risks of TB incidence related to cost and benefit with transmission risks.\u003c/li\u003e\n \u003cli\u003eThe policy evaluation suggests that pre-entry TB screening would have prevented increase in number of new TB cases in Japan, and would in turn have reduced TB healthcare costs and productivity loss.\u0026nbsp;\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"1. Introduction","content":"\u003cp\u003eRespiratory infections are now a major health concern worldwide with the most serious recent lung infection coronavirus disease (COVID-19), declared by the World Health Organization (WHO) a public health emergency of international concern (PHEIC) in January 2020 [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Equally threatening, tuberculosis (TB), a respiratory tract infection [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e], was declared a global health emergency in 1993 [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Up to 2019, TB remains the world\u0026rsquo;s biggest infectious killer, taking more than 1.5\u0026nbsp;million lives in 2018 [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Despite efforts to eliminate TB, countries with low incidence of TB experience high concentrations of cases in at-risk groups as a result of cross-border migration related to globalization [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. High-income countries are now concerned about TB morbidity and mortality, mainly the result of the arrival of individuals born in low income countries with high TB burden [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. The WHO TB framework End TB by 2035 has identified migration by individuals infected with TB as a priority target for action in low incidence countries [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn the past few decades, Japan has been receiving increased numbers of migrants, including visitors, students, and workers from overseas. In 2019, the total number of migrant workers from Nepal in Japan was 91,770, making Nepalese third largest migrant group an increase of 12.5% over the previous year [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. In 2019, Nepal was designated the first country to sign an agreement with Japan for specific-skilled migrant workers, aimed at greater transparency under Japan\u0026rsquo;s immigration control and refugee recognition act [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Although good connections and friendship have been established through development projects for health, education, and tourism between Nepal and Japan [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], the number of migrant workers with TB has increased steadily in recent years [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. In 2018, 1,667 foreign-born migrants with TB were reported in Japan, accounting for 10.2% of Nepalese migrant cases [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. In fact, the yearly increase in number of Nepalese TB cases could increase the number of newly identified TB cases in the native Japanese population [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eStudies indicate that to reduce the number of active TB cases among incoming migrants a pre-entry TB screening program is essential [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. However, Japan has not implemented a mandatory pre-entry TB screening policy for applicant migrants as part of its visa application process, because a pre-entry screening requirement for all migrants would inflict an economic burden on migrants and their home countries, and could even damage the general population's health due to exposure. Nevertheless, due to the seriousness of the issue of migrants with TB, the Japanese government finally decided to introduce a TB pre-entry screening requirement for middle- to long-term applicants from countries with a high number of TB cases (China, Indonesia, Myanmar, Nepal, the Philippines, and Vietnam), effective 2020 [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. However, that action is insufficient in light of the estimated economic impact of the pre-entry TB screening policy on social cost. This study examined the expected cost and benefit of pre-entry TB screening policy on both Japan and Nepal for the period 2014\u0026ndash;2018. The aim of that assessment is to support confidence-building and achieve mutual value for the partner countries.\u003c/p\u003e"},{"header":"2. Method","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Policy scenarios for analysis\u003c/h2\u003e \u003cp\u003eDue to the increased number of TB patients in Japan from high-risk TB incidence countries, Japanese government policy requires pre-entry TB screening to identify migrants with TB [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. TB screening for migrants is implemented as a mandatory part of the visa application procedure targeting five high-burden TB incidence countries, including Nepal [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. In Fig.\u0026nbsp;1, the left flow presents the with policy implementation scenario, where visa applicants should undergo TB screening in their country of origin. TB screening includes a general health check-up (health background check, physical examination, and chest radiography (CXR)), in line with the Japanese Pre-entry TB Screening (JPETS) procedure [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Mycobacterium tuberculosis analysis of three sputum smears and a culture examination are required if the results of the general health check-up suggest active TB. TB diagnosed applicants are not allowed entry into Japan until completion of TB treatment in line with WHO treatment guidelines, as well as the national TB protocol. Applicants are required to provide including appropriate certification that they are free of TB.\u003c/p\u003e \u003cp\u003eThe right flow in Fig.\u0026nbsp;1 presents the current without policy implementation scenario, where clinical TB screening of migrants is conducted within Japan. If the migrants present initial TB symptoms, they take a basic TB clinical examination as part of a general health check-up at clinic or hospital which ensure whether the patient has a suspected TB infection. The migrants must take a Mycobacterium tuberculosis examination of three sputum smears if TB infected. If the sputum test or Polymerase Chain Reaction (PCR) perform positive and the migrants is diagnosed with TB, the physician sends the resident to a TB-specific medical facility or hospital for TB treatment to completion as specified in Japan\u0026rsquo;s TB treatment protocol.\u003c/p\u003e \u003cp\u003e\u0026lt;Figure 1 Policy scenario: TB screening procedure in Nepal and Japan \u0026gt;\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Analytical framework\u003c/h2\u003e \u003cp\u003eThe expected impacts of pre-entry TB screening policy were assessed using cost-benefit analysis approach. The analytical period was set within one year of each of 2014 to 2018, when the pre-entry TB screening policy still had not been introduced. In this CBA, total cost, total benefit and net benefit for Japan and Nepal were measured and these values for \u0026ldquo;\u003cem\u003ewith pre-screening policy\u003c/em\u003e\u0026rdquo; scenario and \u0026ldquo;\u003cem\u003ewithout pre-screening policy\u003c/em\u003e\u0026rdquo; scenario are compared. Cost is measured as the fees for TB screening testing of migrants and TB treatment of patients with TB. Benefit is measured as the avoidance of productivity loss of foreign migrants with TB through by means of incidence risk reduction. Sensitivity analysis is conducted by Monte Carlo simulation. From Japan\u0026rsquo;s perspective, costs are covered by Universal Health Coverage (UHC), which provides effective coverage performance for improving health outcomes and reducing patients cost via equitable health services for all [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Japan publicly funded TB healthcare enables patients with independent residency and national health insurance status to access healthcare services, and the cost of TB-related healthcare services is fully subsidized [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. On the other hand, in Nepal, individuals have to pay the full cost of health services because of insufficient coverage UHC, with some exceptions [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Estimation of active TB population\u003c/h2\u003e \u003cp\u003eThe target population of this study is foreign-born migrants who plan to acquire Foreign Resident status by first applying for a visa for middle- to long-term duration of stay in Japan [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. The foreign residents with TB include those with permanent, study abroad, technical intern, migrant, accompanying family, Japanese spouse, and others Japanese residence status [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Data on foreign residents to Japan and on TB cases in Japan were collected from the Legal Affairs Bureau Japan and the Tuberculosis Surveillance Center Japan, respectively. TB Incidence data of Nepal are sourced from Nepal Demographic and Health Survey and Annual Report by Nepal\u0026rsquo;s Department of Health Service (DHS) [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. The cumulative incidence of TB as an annual figure was calculated by dividing the total population by the number of TB patients predicted under policy implementation during the study period.\u003c/p\u003e \u003cp\u003eFor estimation of the active TB population in Japan under the policy of pre-entry TB pre-screening diagnostic tests, the screening test sensitivity rate is a key prediction value. TB diagnosis depends on the result of sputum smear microscopy test, which can detect either smear-positive or non-infectious [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. We estimate the predicted active TB population with the test sensitivity rate. Kurumi et al. [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] found the sensitivity of sputum smear microscopy test in Nepal to be 62% in 2016. The sputum smear microscopy test is low cost and easy to perform, even in developing countries, while only a few PCR screening methods have been made available in Nepal\u0026rsquo;s health facilities since 2015 [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. On the other hand, the sensitivity of smear microscopy performance in Japan is around 72% [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e] while the positive predicted value (PPV) of PCR is over 95% [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Thus, we adopted PCR as the test for Japan. Detailed statistical formula is described in supplementary Method 1\u0026ndash;1.\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section3\"\u003e \u003ch2\u003e2.3.1 Present Condition\u003c/h2\u003e \u003cp\u003eIn our calculations of the population under the without-policy scenario (i.e. testing conducted in Japan) we used number incidence of TB based on data provided by the Tuberculous Research Institute. In the Japan with-policy scenario, total possible active TB population equals the number of TB false-negative cases in screening tests in Nepal. The difference in predicted active TB cases between with-policy and without-policy can be estimated as the number of active TB cases prevented by implementation of the policy.\u003c/p\u003e \u003cp\u003eLikewise, under the with-policy scenario (i.e. testing conducted in Nepal), 62% of TB patients in Nepal had a positive sensitivity test result and were denied entry to Japan, and 38% of the TB population were false negatives and were allowed entry to Japan. Our analysis predicts the total possible active TB population in Japan without policy by dividing the number of total TB cases detected in the screening tests by the sensitivity test rate to estimate the number of TB patients in the active TB population (including false negatives).\u003c/p\u003e \u003cp\u003eFrom the Japanese perspective, the size of the active TB population is calculated as (Nepalese resident in Japan/ Sensitivity test rate) \u0026times; transmission rate [150%] in the without-policy scenario; and (Nepalese resident in Japan \u0026times; incidence rate in Nepal) \u0026frasl; Sensitivity test rate [62%]-TB population \u0026times; Incidence rate in Nepal) \u0026times; transmission rate [150%] in the with-policy scenario.\u003c/p\u003e \u003cp\u003eFrom the Nepalese perspective, there have been active Nepalese TB cases in Japan, and thus no direct benefit for Nepal in the without-policy scenario; the size of active TB population is calculated as (Nepalese resident in Japan \u0026times; incidence rate in Nepal / Sensitivity test rate [62%]-False negative cases) \u0026times; transmission rate in With-policy scenario.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Expected impact on the cost and benefit\u003c/h2\u003e \u003cp\u003eThe expected impact of the different hypothetical policy scenarios can be measured by comparing cost and benefit of \u0026ldquo;with policy\u0026rdquo; and \u0026ldquo;without policy\u0026rdquo; for both Japan and Nepal (Fig.\u0026nbsp;2). There are two national perspectives, with-policy and without-policy. Thus, we have a prediction of the outcomes of the two scenarios, in terms of cost, benefit, and net benefit (benefit minus cost) monetized in local currency with consideration of inflation rate.\u003c/p\u003e \u003cp\u003e\u0026lt;Figure 2 Policy scenario: Policy simulation algorithm \u0026gt;\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section3\"\u003e \u003ch2\u003e2.4.1 Cost of TB screening test\u003c/h2\u003e \u003cp\u003eThe full cost is presented as local prices in US dollars with inflation and the exchange rate of each year, according to Financial Statistics of the International Monetary Fund (IMF) [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. All costs were reported within each year from 2014 to 2018 as total social cost from each national perspective. The data for Japanese local cost including cost of TB screening and treatment is taken from National Database (NDB) [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. TB test prices in Nepal are drawn from the guidance for TB testing by UK [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e], and treatment cost is quoted from Gurung et al. [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Costs of TB testing and treatment reflect the different approaches to screening and treatment under WHO guidelines for treatment criteria and National TB methodology. The screening cost consists of general health check-up, examination of three sputum smears, PCR, chest radiography, and standardized basic clinical TB examination. Indirect costs of transportation, caregiver or health worker time, etc. are not within the scope of our analysis [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section3\"\u003e \u003ch2\u003e2.4.2 Cost of TB treatment\u003c/h2\u003e \u003cp\u003eThe cost of the TB treatment drug regimen is calculated as the total number of tablets required for six months\u0026rsquo; treatment with the first-line drugs specified in both the WHO guideline and national TB methodology. The first-line drugs include Rifampicin (RFP), Pyrazinamide (PZA), Isoniazid (INH), and Rifabutin (RBT), as per the 2018 Japanese TB treatment guideline [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. We calculated the cost of these drugs taken three times a day for six months; pre-treatment phase to the intensive period as the TB treatment in Nepal [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section3\"\u003e \u003ch2\u003e2.4.3 The benefit by avoidance of productivity loss\u003c/h2\u003e \u003cp\u003eCost of TB treatment includes medical cost and time loss resulting from undertaking TB treatment for a minimum of six months. The treatment requires that the patient be isolated, which would reduce the patient\u0026rsquo;s income [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. In that light, the assumption of benefit considers the avoidance of productivity loss by both patient and nation through incidence risk reduction via policy implementation. We estimate wages in Japan using sectoral data from the Ministry of Health, Labour, and Welfare in Japan [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e], and in Nepal using monthly GNI per capita obtained from IMF [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e] (constant LCU: local currency unit for one year). Estimation of income of student dependents of foreign residents is based on that projected wage.\u003c/p\u003e \u003cp\u003eOur primary estimation of the net present value (NPV) of implementation of the policy equals the difference between the present value of the social benefit (PVsb) and the present value of social cost (PVsc). From the Japanese perspective, NPV\u0026thinsp;=\u0026thinsp;0-Total implement fee།Total productivity loss; while form the Nepalese perspective, NPV\u0026thinsp;=\u0026thinsp;0།Incremental test fee།Total treatment fee།Total productivity loss. In that light, we need to estimate the impact of implementation of policy as an incremental net social benefit (NSB)\u0026thinsp;=\u0026thinsp;Net benefit in With-policy scenario །Net benefit in Without-policy scenario. We provide the statistical formula in more detail in supplementary Method 1\u0026ndash;2.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e2.5 Sensitivity analysis\u003c/h2\u003e \u003cp\u003eThe NPV is likely uncertain due to changes in the value of key input parameters, uncontrollable factors of epidemics, such as the chance of infecting other people could affect the benefit and cost that would be anticipated by the proposed policy. In Monte Carlo simulation of TB transmission impact, the probability of distribution in the population is a key input parameter for all essential uncertain quantitative estimations. For instance, the interval of sensitivity analysis in Cyprus presented 0\u0026ndash;10% and 10\u0026ndash;25% [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Given the fact of large economic impacts such as inflation, deflation and unemployment rate in Nepal and Japan, WHO key facts suggest that people carrying TB bacteria have a 5\u0026ndash;15% chance of falling ill with TB [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. We thus calibrate the parameters of increase and/or decrease of the incidence of TB probability over the intervals 0\u0026ndash;15 and 15\u0026ndash;30%.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003e2.6 Conceptualization toward burden sharing\u003c/h2\u003e \u003cp\u003eThe With-policy scenario requires Nepal to take on the additional costs of TB screening test of migrants to Japan. In high burden TB countries, out-of-pocket (OOP) expenditures have accounted for at least 45% of total health expenditures [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e], and more than 50% in Nepal [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e] due the absence of UHC [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. They are suffering increased health-related financial difficulties in terms of OOP expenditure and access to healthcare. The catastrophic cost of healthcare (i.e. TB detection, care and treatment) in high TB burden countries called for affordable TB-specific interventions and sustainable mechanisms for financing those interventions, as well as progress under UHC [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. Thus, it would be more equitable to develop a methodology of burden sharing so as to consider the net benefit of Japan and Nepal in calculations of appropriate share of investment transfer, so as to maximize Nepal\u0026rsquo;s incentive to develop public health infrastructure for TB screening tests, care and treatment for disease prevention and control.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cp\u003eThe predicted numbers of active TB cases and NSB for workers/students (2014 to 2018) in Japan and Nepal are shown in Table\u0026nbsp;1. For Japan, the predicted number of active TB cases increased for both with- and without-policy. Still, the percentage of active TB cases among students is higher than that among workers. Significantly, the outcome of fewer cases of active TB in the With-policy case constitutes reduction of active TB incidence risk. In addition, increased worker NPV under the TB screening policy in 2014 was estimated at JPY 118.4\u0026nbsp;million (USD 1.1\u0026nbsp;million) and increased to JPY 332.1\u0026nbsp;million (USD 3.0\u0026nbsp;million) in 2018. In turn, the result of the increase of student NPV was a positive, JPY 203.4\u0026nbsp;million (USD 1.9\u0026nbsp;million) in 2014, and grew substantially to JPY 320.9\u0026nbsp;million (USD 2.9\u0026nbsp;million) in 2018. The increase in NPV was greater than zero, which implies that the implementation of the TB screening policy in Japanese society could produce a significant benefit in terms of prevention of increased number of cases of active TB. For Nepal, the predicted number of Nepalese with active TB increased, with student incidence greater than that for workers. Student NPV decreased from -NPR 384.4\u0026nbsp;million (USD \u0026minus;\u0026thinsp;3.9\u0026nbsp;million) in 2014 to -NPR 887.0\u0026nbsp;million (USD-8.1\u0026nbsp;million) in 2018, where pre-entry TB screening policy was implemented. Total NPV for Nepal was negative due to the total cost being higher than the benefit (productivity loss), which indicates the imposition of the burden of direct cost, including testing and treatment costs, on Nepalese society.\u003c/p\u003e \u003cp\u003e\u0026lt;Table\u0026nbsp;1 Number of predicted active TB cases and net social benefit for workers/students in Japan and Nepal\u0026gt;\u003c/p\u003e \u003cp\u003eWe applied 0\u0026ndash;15 and 15\u0026ndash;30% sensitivity analysis in a Monte Carlo simulation as the secondary transmission rate on incremental NPV for both perspectives in order to address parameter difference uncertainty. The NPV for Japan increased depending on the TB incidence rate in each interval on the transmission scale. When a high 15% increase in TB transmission rate might indicate a high risk of becoming infected, the output would increase student NPV from JPY219.0\u0026nbsp;million (USD 2.1\u0026nbsp;million) to JPY345.4\u0026nbsp;million (USD 3.1\u0026nbsp;million) for 2018 (Table\u0026nbsp;2). In contrast, the negative value of NPV distribution among Nepalese students increased to minus 1\u0026nbsp;billion NPR (USD 8.7\u0026nbsp;million) in 2018 (Table\u0026nbsp;3)\u0026mdash;very costly when the risk of transmission rates increased by more than 30%. We provide Fig.\u0026nbsp;1 in more detail in Supplementary Result 2\u0026thinsp;\u0026minus;\u0026thinsp;1 and Fig.\u0026nbsp;2 in Supplementary Result 2\u0026ndash;2.\u003c/p\u003e \u003cp\u003e\u0026lt;Table\u0026nbsp;2 Sensitivity analysis of net present value in Japan \u0026gt;\u003c/p\u003e \u003cp\u003e\u0026lt;Table\u0026nbsp;3 Sensitivity analysis of net present value in Nepal \u0026gt;\u003c/p\u003e \u003cp\u003eThe scenario results show that the implementation of pre-entry TB screening for applicants for Japanese visas could involve significant cost for Nepal (Fig.\u0026nbsp;3). We provide Table\u0026nbsp;1 in more detail in supplementary Result 2\u0026ndash;3.\u003c/p\u003e \u003cp\u003e\u0026lt;Figure 3 Net present value for Nepalese workers and students in Nepal and Japan \u0026gt;\u003c/p\u003e \u003cp\u003eAs shown above, Nepal bears a much heavier burden than Japan. Significantly, the difference in NPV is counterbalanced by the burden of cost allocation, which is accentuated by the huge economic gap between two countries. Level of fiscal burden should be taken into consideration under a fair sharing mechanism between collaborating countries. Although, methods for determining burden-sharing rate for global health aid projects have not yet been developed, our net benefit scenario results could be considered as a net benefit contributing to health equality.\u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003e4.1 Policy implications\u003c/h2\u003e \u003cp\u003eAssessment of Nepal's and Japan's expected costs and benefits of resulting from Japan\u0026rsquo;s pre-entry TB screening policy implementation for prospective Nepalese residents of Japan should be conducted with consideration of social value in terms of monetization. Our multi-dimensional evaluation simulates empirically scenarios reflecting both perspectives, so as to examine the potential outcome of implementation of the new policy design in Japan. Specifically, our approach measures the social values of pre-entry TB screening strategy. The simulation suggests that pre-entry TB screening would have prevented about 181 active TB cases in Japan for 2018, and would in turn have reduced TB screening costs and worker productivity loss\u0026mdash;welcome outcomes from the Japanese perspective. This encores that the appropriate pre-entry TB screening policy for that group has been discussed [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e], would contribute to the prevention, and eventually elimination, of TB in Japan.\u003c/p\u003e \u003cp\u003eOverseas LTBI screening and treatment for refugees and foreign-born residents in the US could serve as a model for the reduction of active TB by domestic health prevention management [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]. Current TB cross-border management issues are inadequate for TB incidence risk reduction, infection control, collaboration, and the sharing of global data [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]. The reduction of risk of TB incidence is recommended as a policy-based practice within public health emergency management at every level. National health prevention and disease control could serve as health emergency management instruments in neighboring countries \u003cem\u003evis\u003c/em\u003e-\u0026agrave;-\u003cem\u003evis\u003c/em\u003e trans-border migration.\u003c/p\u003e \u003cp\u003eDue to weak public and global health emergency management and the increasing number of foreign residents with TB worldwide, cross-border infectious disease transmission is now a major human security concern, even threatening international peace and security [\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e]. Human security is now recognized in Japan as a central concern; Japan must promote social resilience through international health cooperation [\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e]. Our scenario results estimate that pre-entry TB screening testing within Nepal could have been identified 137 TB cases among 42,346 visa applicants from Nepal in 2018; those individuals could have undergone TB treatment in Nepal until issued TB-free certificates.\u003c/p\u003e \u003cp\u003eAlthough pre-entry TB screening strategy could contribute to the establishment of aggressive TB screening and treatment in Nepal, it could have a negative impact on TB-related expenditure for households with insufficient healthcare coverage [\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e]. WHO's End of TB strategy identified reduction of TB-affected household expenditures as a priority means of preventing catastrophic economic costs of TB in low income countries [\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e]. The implementation of TB screening pre-entry to Japan would reduce TB incidence risk, and early TB diagnosis prior to entry to Japan would ensure elimination of a substantial proportion of detected TB cases.\u003c/p\u003e \u003cp\u003eIn Japan, there remains little evidence of sufficient awareness within the target population (Nepal) of TB control, prevention and treatment. The target population diagnosed with TB could be subjected to considerable disease-related burden, including loss of income, discretionary time for TB care, and treatment cost difficulties related to lack of health coverage. Fair sharing of net benefits as public goods is likely to improve health equity, assuming cooperation by developing countries [\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e]. According to some empirical studies, the burden-sharing required to achieve the global health target will call for large efforts by multi-stakeholders [\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e]. The outbreak of the Covid-19 global pandemic has confirmed that policy implementation reflecting migrant home and destination is indispensable for a resilient public health system and infrastructure for financing holistic health diplomacy development [\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003e4.2 Limitations and future perspective\u003c/h2\u003e \u003cp\u003eTB has been designated an infectious disease by law in Japan, with provision of full coverage of treatment costs. In the absence of such system for Nepal, measures of willingness to pay and shadow price to estimate the value of a statistical life (VSL) are not applied in this study. Nevertheless, this study clarifies the relationship between economic impact and Japanese pre-entry TB screening policy aimed at the elimination of TB. The empirical estimates elucidate the spillover effect from health system reinforcement through international collaboration, while technology application is expected to enhance the interpretation of the change from the value chain in the both countries.\u003c/p\u003e \u003cp\u003eRegarding the public health impact of infectious disease exacerbated by cross-border issues, implementation of the policy would enhance the effect of TB incidence risk reduction and cost-saving by foreign born residents of Japan. Migrant nations subject to the implementation of the policy, especially low-income countries, would bear the cost of TB testing and treatment. Hence, establishing a burden-sharing mechanism would generate a spillover effect on population health and reduce vulnerability to financing shock for the migrant county, in turn deepening the interdependence between Nepal and Japan in terms of inclusive development for the elimination of TB.\u003c/p\u003e \u003c/div\u003e"},{"header":"5. Conclusions","content":"\u003cp\u003eThis study estimated the expected policy implementation costs and benefits of pre-entry TB screening testing and treatment targeting Nepalese born residents of Japan, a high TB burden country. In order to give consideration to the different perspectives on the policy implementation scenarios, we calculated the risks of TB incidence related to cost and benefit with transmission risks, as measures of policy effectiveness in each country. We reason that effective TB infection control could help reduce the output value of productivity loss, which would in turn lead to cost-saving the implementation of pre-entry TB screening policy in Japan.\u003c/p\u003e\n\u003cp\u003eBy identifying an optimal combination of expected cost and benefit, it possible to give stakeholders various options for TB countermeasures both nationally and internationally. Policy makers understand that it is vital to provide information and guidance regarding the recognized impacts, considering different perspectives, of this policy setting process. It should be noted that the simulation framework could also be applied to the design of Covid-19 countermeasures. \u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe sincerely express our gratitude to the former Director General of the Bureau of International Health Cooperation at the National Center for Global Health and Medicine (NCGM), Japan, for his invaluable support and guidance throughout this research.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding Statement\u003c/strong\u003e\u003cstrong\u003e:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Publish declaration:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics and Consent to Participate declarations:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical and conflict of interest statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe used secondary health data from the Nepal Demographic and Health Survey and the Nepal Department of Health Services (DHS) Annual Report [23]; and from Japan\u0026rsquo;s Legal Affairs Bureau and Tuberculosis Surveillance Center. It is not possible to identify individual health information of participants from the data, so this study did not require ethical approval or conflict of interest statements.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eWorld Health Organization. Statement on the second meeting of the International Health Regulations (2005) Emergency Committee regarding the outbreak of novel coronavirus (2019-nCoV)\u0026rsquo;. Newsroom detail, 30 January 2020. Available from https://www.who.int/news-room/detail/30-01-2020-statement-on-the-second-meeting-of-the-international-health-regulations-(2005)-emergency-committee-regarding-the-outbreak-of-novel-coronavirus-(2019-ncov). [Accessed January 28 2021].\u003c/li\u003e\n \u003cli\u003eBrown JS, Lipman MC, Zar HJ. What\u0026rsquo;s new in respiratory infections and tuberculosis 2008-2010. Thorax, 2012;67:350-354.\u003c/li\u003e\n \u003cli\u003eWHO Global Tuberculosis Programme\u0026lrm;. 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Lancet, 2020; 396:e57.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 to 3 are available in the Supplementary Files section\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"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":"","lastPublishedDoi":"10.21203/rs.3.rs-5766264/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5766264/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjectives:\u003c/strong\u003eThis study examined the cost and benefit impact of the introduction of pre-entry tuberculosis (TB) screening policy, including testing and treatment for Japan and Nepal from 2014 to 2018.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003eThis study used data from the Nepal Demographic and Health Survey; and from Japan’s Legal Affairs Bureau and Tuberculosis Surveillance Center. We used cost-benefit analysis to examine the effect of the pre-entry TB screening policy. Total cost, total benefit and net benefit for both countries were compared for the policy scenarios “With” and “Without”, using net present value (NPV). In order to address parameter difference for uncertainty, we conducted sensitivity analysis using Monte Carlo simulation with secondary transmission rate.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eBetween 2014 and 2018 in Japan, NPV of Nepalese student increased from USD 1.9 million to USD 2.9 million; likewise, NPV of Nepalese workers grew from USD 1.1 million to USD 3.0 million. The increase in NPV was greater than zero, meaning that the implementation of the policy could produce a benefit for Japan regarding prevention of increase in number of new TB cases. In Nepal, the predicted number of foreign migrant applicants with newly diagnosed TB increased. Total NPV for Nepal was negative since total cost was greater than the benefit, suggesting added burden of direct TB cost.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e Implementation of pre-entry TB screening policy for foreign migrants arriving in Japan from Nepal with high TB burden would achieve efficient cost-saving through reduction of number of newly diagnosed TB cases including those with transmission risk.\u003c/p\u003e","manuscriptTitle":"Cost-Benefit Analysis of Pre-Entry Tuberculosis Screening Policy: Nepalese and Japanese Perspectives","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-01-13 17:33:47","doi":"10.21203/rs.3.rs-5766264/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":"14fe1f75-1a9b-4658-b62e-ae879fdb480f","owner":[],"postedDate":"January 13th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-01-20T11:08:16+00:00","versionOfRecord":[],"versionCreatedAt":"2025-01-13 17:33:47","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5766264","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5766264","identity":"rs-5766264","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}