Barriers and Facilitators to the Adoption of Multiple First-Line Therapies for Management of Uncomplicated Malaria in Tanzania: A Multi-Method Qualitative Study

Barriers and Facilitators to the Adoption of Multiple First-Line Therapies for Management of Uncomplicated Malaria in Tanzania: A Multi-Method Qualitative Study | 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 Barriers and Facilitators to the Adoption of Multiple First-Line Therapies for Management of Uncomplicated Malaria in Tanzania: A Multi-Method Qualitative Study Hafidhi Hussein Ntissi, Annabel Itaeli, Raphael Z. Sangeda, George Msema Bwire This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7711744/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 04 Dec, 2025 Read the published version in Malaria Journal → Version 1 posted 12 You are reading this latest preprint version Abstract Background: Malaria remains a major public health burden in Tanzania, where Plasmodium falciparum accounts for 96% of infections and children under five years experience the highest mortality. The emergence of kelch13 mutations and partial resistance to artemisinin derivatives poses a threat to the sustainability of artemisinin-based combination therapies (ACTs). Reliance on artemether–lumefantrine (ALU) as the dominant first-line treatment increases selective pressure. The World Health Organization recommends multiple first-line therapies (MFT) to slow the development of resistance. This study examined the barriers, facilitators, and potential strategies for adopting MFT for uncomplicated malaria in Tanzania. Methods: A multi-method qualitative study was conducted. A desk review of national malaria data (2020–2024) was conducted to examine trends in incidence, mortality, and treatment outcomes. Data on importation from the national medicine regulatory authority (2021–2025) were analyzed to assess the ACT importation pattern. The desk review provided epidemiological and pharmaceutical context for qualitative enquiry. Semi-structured interviews were conducted with purposively selected participants, including policymakers, regulators, supply chain managers, and frontline healthcare providers. Interviews were transcribed and thematically analyzed using Braun and Clarke's framework with NVivo software. Results: Between 2020 and 2024, malaria cases declined from approximately 8.9 million to 7.2 million before resurging to 8.1 million in 2023; deaths followed a similar trend. Children under five consistently bore a higher burden, representing 34% of all cases and 46% of deaths. While case incidence in this age group declined significantly (p=0.011), mortality showed no improvement (p=0.802). Importation data revealed ALU comprised 73.5% of all antimalarial imports, compared to 12% for artesunate, 6% for artemether, and only 2.6% for dihydroartemisinin–piperaquine, highlighting limited diversification. Qualitative findings identified barriers, including the high cost of alternative artemisinin-based combination therapies (ACTs), limited provider training, and weak supply chains. Facilitators, on the other hand, demonstrated a strong political commitment, engaged in capacity-building initiatives, and relied on therapeutic efficacy and pharmacovigilance data to inform their approach. Conclusion: MFT presents a promising strategy for prolonging ACT efficacy and enhancing malaria case management in Tanzania. However, financial constraints, import dependence on ALU, and inadequate provider preparedness limit implementation. Successful adoption will require diversification of ACT imports, strengthening supply chains, sustained capacity-building, and embedding surveillance and regulatory data into policy decision-making. Malaria Antimalarials Multiple-fist line treatment Tanzania Figures Figure 1 Figure 2 Background Malaria is one of the diseases that has the highest number of cases and deaths globally. It accounts for 3% of cases and 4.1% of global deaths in 2020. In Tanzania, Plasmodium falciparum is the primary causative agent of malaria, accounting for 96% of cases, while the remaining 4% are attributed to Plasmodium vivax and Plasmodium ovale . 93% of the Tanzanian population is at risk of malaria transmission, with children under the age of five years being the most affected group ( 1 ). The prevalence of malaria in children under five years differed across various regions, ranging from less than 1% in areas such as Zanzibar, Kilimanjaro, and Arusha to 20% in Mtwara and 23% in Tabora ( 2 ). The emergence of partial resistance of artemisinin derivatives and ACT partner drugs such as lumefantrine and piperaquine has recently emerged, especially in South East Asia, in countries like Cambodia ( 3 ). In Africa, partial resistance has been observed in Rwanda and Uganda, characterized by delayed parasite clearance and an increase in treatment failure. A molecular surveillance study conducted in Tanzania revealed the presence of the artemisinin resistance marker kelch13 (k13), specifically therg561His mutation, in the Kagera region ( 4 ). Parasites harboring this mutation have an advantage under the current regimen due to their high transmissibility and improved parasite fitness ( 5 ). Due to the risk of artemisinin resistance spreading to sub-Saharan Africa, malaria control strategies must be adjusted by optimizing current ACT therapy. The simultaneous use of multiple artemisinin-based malaria combinations has been suggested ( 6 ). For example, in the year 1990, mefloquine resistance, a drug co-formulated with ACT, was observed in Thailand and Myanmar, which manifested as slow parasite clearance ( 7 ). Many countries' national policies recommend the use of a single first-line therapy for most clinical cases in the management of uncomplicated malaria, despite the availability of many drugs to manage malaria. This "wait and switch" process tends to overwhelm public healthcare systems, leading to increased morbidity and mortality 8). For example, the Tanzania standard treatment guideline recommends the use of artemether-lumefantrine (ALU) as the first-line treatment and dihydroartemisinin-piperaquine (DHP) in cases where ALU isn't effective or contraindicated. No other drug is listed in the guidelines apart from these two that can be used in the management of uncomplicated malaria in Tanzania. With the possibility of developing alternative drugs being unlikely for ACTs in the short term, it is essential to preserve the therapeutic lifespan of available ACTs. The WHO Global Technical Strategy for Malaria 2016–2030 recommends formulating strategies that take into account the epidemiology and heterogeneity of malaria in the country ( 9 ). This can be achieved by dividing the country into different strata and implementing targeted interventions within those stratified groups. For example, a particular region could employ a specific ACT combination, while another region uses a different combination. Multiple first-line treatment (MFT) is defined as a drug policy in which several therapies are made available for clinicians to choose by clinicians to manage uncomplicated malaria in a society. This strategy can be implemented in various ways, including segmentation and rotation. The segmentation approach aims to stratify the ACT market into distinct age groups, including pediatrics, pregnant women, and adults, by geographical regions. The rotation approach seeks to switch the ACT regimen after a specific period by monitoring the efficacy of the currently available medications. The drugs are made available in both private and public health facilities. In various studies, it has been demonstrated that employing multiple first-line strategies offers several benefits, including slowing down the evolution of resistance by increasing the variability of drugs in the parasite's environment and a reduction in overall selection pressure for resistance to that particular drug ( 8 ). Offering multiple first-line therapies not only allows for flexibility in treating patients with specific needs or drug sensitivities but also helps distribute selective pressure across different drugs, thereby slowing the development of resistance. Moreover, having a range of effective first-line options strengthens healthcare systems by providing more adaptable, regionally tailored responses to malaria, which is crucial for sustainable control and eradication efforts. Adopting multiple treatments thus ensures more resilient, accessible, and effective malaria care, particularly in resource-limited settings that face high disease burdens. However, only ALU is widely used as a first-line treatment in many endemic areas, limiting insights into the practical application of alternative regimens. Therefore, this study aimed to examine the barriers to adopting a broader range of first-line treatments, as well as the facilitators that could enable their integration into case management of uncomplicated malaria in Tanzania. Study design, period and population A multi-method qualitative study was undertaken between April and June 2025 to explore the barriers, facilitators, and strategies for adopting MFT for uncomplicated malaria in Tanzania. The study combined a desk review of epidemiological and pharmaceutical data with key informant and in-depth interviews. This design allowed for the integration of documentary evidence with stakeholder perspectives to ensure contextual relevance. The desk review was conducted to provide epidemiological and pharmaceutical context for the qualitative enquiry. National Malaria Control Programme (NMCP) data, covering the period from January 2020 to December 2024, were analyzed to assess malaria trends, including annual cases, deaths, and the under-five burden. These data were disaggregated by age group (< 5 years versus ≥ 5 years) and analysed using descriptive statistics and simple trend tests to identify temporal patterns. Additionally, secondary data on antimalarial imports between January 2021 and July 2025 were obtained from the Tanzania Medicines and Medical Devices Authority (TMDA). The desk review served two purposes: (i) to provide a descriptive overview of the malaria burden and treatment landscape in Tanzania, and (ii) to guide the design and interpretation of the qualitative interviews by highlighting priority gaps and contextual drivers. Semi-structured interviews were conducted with purposively selected participants from the domains of malaria policy, regulation, supply chain, and healthcare delivery. Eligibility criteria included a minimum of 12 months' experience in malaria case management, health policy, or pharmaceutical logistics. Participants were drawn from both the public and private sectors, including policymakers, regulatory officials, supply chain managers, and frontline healthcare providers (doctors, nurses, and pharmacists). Sample size and sampling techniques The study planned 10 key informant interviews (KIIs) with stakeholders, including policymakers and implementers, and five in-depth interviews (IDIs) with healthcare workers (doctors, pharmacists, and nurses) from hospitals in Dar es Salaam and Dodoma. Participants were purposively selected based on expertise in malaria case management. KIIs were chosen to capture diverse institutional perspectives on MFT, while IDIs provided insights from frontline healthcare workers. Interviews continued until data saturation was reached, ensuring credibility and completeness. Data collection procedures Semi-structured interview guides were developed in English and translated into Kiswahili to ensure clarity, inclusivity, and ease of expression for participants. Kiswahili, being the national language, allowed respondents to communicate freely and provide richer, more detailed insights without language barriers. The guides contained open-ended questions to explore barriers, facilitators, and strategies for adopting a multi-first-line treatment strategy for malaria in Tanzania. They were developed deductively from study objectives, literature ( 10 – 13 ), desk review, and expert input, and refined as new issues emerged. KIIs and IDIs were conducted in informants' offices at convenient times. Each interview lasted 30–60 minutes and was facilitated by a researcher with support from a co-researcher who took notes and audio recordings. Verbal and non-verbal responses were captured, and debriefings were held after each session to ensure quality and identify emerging issues. Data analysis Descriptive statistics were used to summarize malaria cases, deaths, and patterns of antimalarial importation. Annual malaria case counts and deaths were disaggregated by age group (< 5 years vs. ≥5 years) and presented both as absolute numbers and proportions of the national burden. Trends from 2020 to 2024 were visualized using line and bar graphs. Comparisons of malaria burden between children under five years and individuals aged five years and above were assessed using the Chi-square test for independence. Temporal trends in the proportion of cases and deaths attributed to under-fives between 2020 and 2024 were examined using Pearson's correlation as an approximation of a trend test. To evaluate the change in under-five mortality between 2022 and 2023, a two-proportion z-test was applied. Statistical significance was set at p < 0.05. All quantitative analyses were conducted using R software. Qualitative data from KIIs and IDIs were analyzed using inductive thematic analysis guided by Braun and Clarke's framework (2006) ( 14 ). This approach enabled themes to emerge directly from the data, while addressing the study objectives of identifying barriers, facilitators, and strategies for adopting MFT for malaria treatment. All interviews were conducted via Zoom due to logistical constraints, audio-recorded with participants' consent, and transcribed verbatim in Kiswahili to ensure clarity, openness, and cultural relevance. Field notes were incorporated to enrich contextual detail. Coding and theme development were performed in Kiswahili to preserve meaning, and only representative quotes and final themes were translated into English for reporting. Using NVivo software (version 15), coding was undertaken independently by two researchers, followed by the development of a shared codebook in which categories were consolidated into overarching themes and subthemes. Data collection and analysis were conducted concurrently until thematic saturation was achieved. Rigor was maintained through triangulation, peer debriefing, and reflexive discussions ( 16 ). Credibility was strengthened through purposive sampling and the use of Kiswahili, which allowed for the capture of richer narratives. Dependability was achieved by adhering to standardized guides, while confirmability was supported through detailed documentation and reflexivity. Transferability was ensured by providing comprehensive descriptions of the study setting, participants, and procedures. Results Desk Review Findings Antimalarials Importation in Tanzania (January 2021 - July 2025) ALU dominated the market, accounting for 73.5% of all imports, followed by artesunate (12%), artemether (6%), and SP (4.9%). Smaller shares were recorded for DHP (2.6%) and Quinine (0.9%), while other medicines (primaquine, atovaquone + proguanil, and hydroxychloroquine) together accounted for less than 0.5% (Fig. 1). Malaria Cases and Deaths in Tanzania (January 2020 – December 2024) Between 2020 and 2024, under-five children consistently bore a disproportionate malaria burden compared to older age groups, with differences in both cases and deaths highly significant (p < 0.001). Analysis of temporal trends showed that the proportion of cases among under-fives declined significantly over time (p = 0.011), while the proportion of deaths in this age group showed no significant change (p = 0.802). Although the number of under-five malaria deaths increased between 2022 and 2023, this rise was not statistically significant (p = 0.159)(Fig. 2 ). Qualitative Findings Description of data collection activities A total of 12 qualitative interviews were conducted with various stakeholders between April and June. These consisted of six key informant interviews and six in-depth interviews. The interviews consisted of a diverse group of stakeholders, including healthcare providers, regulatory officials, policy formulators, and supply chain personnel. The KIIs involved interviewing key personnel from the NMCP, the President's Office - Regional Administration and Local Government (PO-RALG), and the Medical Stores Department (MSD). The in-depth interviews (IDIs) involved interviewing healthcare workers, including medical doctors, pharmacists, and nurses. The average duration of the IDIs was 23 minutes, with the shortest one lasting 15 minutes and the longest one lasting 39 minutes. The KII's duration ranged from 24 to 37 minutes, resulting in an average of 31 minutes. These interviews took longer due to individual expertise and the vast amount of information they provided during the interviews. Interviewed participants' characteristics The study involved twelve ( 12 ) participants recruited from a broad spectrum of health institutions across Tanzania, including regional referral hospitals and prominent government agencies such as the NMCP and the MSD. Participants' ages ranged from 29 to 54 years, with a median age of 38 years. The gender distribution was relatively balanced, with a slight predominance of female participants. The participants represented diverse professional backgrounds, including medical doctors, nurses, pharmacists, policy analysts, and supply chain specialists. This professional heterogeneity facilitated the inclusion of multiple stakeholder perspectives pertinent to malaria case management. On average, participants had six ( 6 ) years of professional experience, indicating substantial exposure to health service delivery systems. Respondents were drawn from both public and private healthcare settings, including institutions such as Bugando and Singida Regional Referral Hospitals, the Aga Khan Hospital, and key government offices. This institutional diversity enabled the study to capture insights from both clinical and policy implementation contexts. The educational level of participants was evenly distributed between those with bachelor's degrees (n = 6) and master's degrees (n = 6), reflecting a high level of technical expertise and academic engagement. The variation in educational backgrounds contributed to the analytical richness and credibility of the study's findings, particularly regarding the feasibility and adoption of multiple first-line therapies for malaria management in Tanzania ( Table 1 ). Emerging themes from qualitative analysis Table 1 Themes and sub-themes emerged from qualitative interviews Themes Sub-themes Cost and financial barriers • High cost of alternative therapies • Inadequate NHIF coverage • Donor dependency and financial instability Knowledge and training gaps • Familiarity and preference for ALU • Social misconceptions about alternatives • Weak STG implementation at lower levels • Poor adherence and understanding at the patient level Supply chain and logistics barriers • Unreliable drug supply and logistics • Inadequate data for decision-making • Unavailability of medicines Government and stakeholders' commitment • Existence of national guidelines and TWGs • Political will and institutional commitment • Technical studies supporting MFT • Stakeholder engagement and coordination • Phased rollout and implementation • There's a transition guideline that shows clearly the steps to adopt new therapies. Training and capacity building • Training and capacity building • Social behavior changes communication (SBCC) Data-driven decision making • Data-driven policy and procurement • Engagement of research institutions Barriers to MFT adoption Cost and financial barriers The cost of alternative ACTs, other than ALU, has been identified as a significant barrier to implementing MFT strategies for the management of uncomplicated malaria in Tanzania, both at the individual and national levels. At the individual level, ACTs such as DHP are considerably more expensive, with costs ranging from three to four times that of ALU. At the national level, ALU benefits from government subsidies, whereas alternative therapies do not. Compounding the challenge, several key donors—most notably the President's Malaria Initiative (PMI)—have begun withdrawing support for malaria programs. This shift highlights the potential financial constraints Tanzania may face if it adopts an MFT approach. Representative quotes: "A single dose of Dihydroartemisinin-piperaquine is approximately four times the unit cost of Artemether-Lumefantrine". __Male, 54 years, Program Manager "Funders like the President's Malaria Initiative have pulled back, and we're not sure if the Global Fund will continue supporting us. These setbacks have slowed down progress toward adopting Multiple First-line Treatment." __Female, 45 years, Supply chain officer "We rely on the Global Fund to procure Artemether Lumefantrine – without it, sustainability is a concern." __Female, 47 years, Malaria Unit Head Knowledge and training gaps It was observed that many healthcare workers possessed limited knowledge and had received minimal training on ACTs other than ALU and DHP, which are the most commonly used and recommended in the Standard Treatment Guidelines and National Essential Medicines List (STG-NEMLIT). This knowledge gap presents a major obstacle to the successful adoption of MFT strategies. When healthcare providers are unfamiliar with alternative therapies, they are unlikely to prescribe or procure them for use in their facilities. At the patient level, limited awareness and understanding of proper adherence to antimalarial medications—particularly after discharge—further compounds the challenge. Without sufficient patient education, the introduction of new therapies may lead to poor adherence, ultimately undermining the effectiveness of MFT implementation. Representative quotes: "Most of us have never handled Artesunate Amodiaquine or Dihydroartemisinin Piperaquine. We only know Artemether Lumefantrine, so exposure and proper instruction are critical." __Male, 32 years, Medical Doctor "Sometimes patients don't return or don't understand the importance of completing the dose, and that compromises adherence." __Female, 51 years, Nurse "When healthcare providers are only trained on a single treatment regimen like Artemether Lumefantrine, they tend to hesitate or feel unsure about using other available Artemisinin Combination Therapies. Without proper training on alternatives, it becomes difficult to adopt new treatment strategies." __Male, 34 years, Monitoring & Evaluation Officer Supply chain and logistics barriers Supply chain and logistical challenges were widely cited as significant barriers to implementing MFT for uncomplicated malaria in Tanzania. Government health facilities depend heavily on the MSD for drug supply, yet MSD often distributes only one type of ACT, which is ALU. This practice not only limits treatment options but also contradicts the principle of MFT, which requires the simultaneous availability of multiple therapies. Additionally, delays in drug distribution, limited forecasting capacity, and poor coordination among stakeholders also contribute to the logistical complexity. Inadequate infrastructure, transportation issues, and the absence of robust systems for post-marketing surveillance further exacerbate these barriers. Representative quotes: "We distribute based on quantified demand – switching drugs means recalibrating logistics." __Female, 31 years, Supply chain officer "We rely on the Medical Stores Department for drug supplies. Sometimes, they stock one drug type for months, and then it runs out. That defeats the purpose of having options." __Male, 35 years, Hospital Pharmacist "The biggest issue is the supply and logistics system—it relies heavily on a single supplier." — Male, 32 years, Medical Doctor "We are not directly involved in procurement processes. We rely on the Medical Stores Department and the central level to ensure availability." __Female, 47 years, Malaria Unit Head Facilitators and Strategies to MFT adoption Government and stakeholders' commitment The Government of Tanzania has demonstrated strong political commitment toward malaria eradication, as evidenced by its active engagement with a wide range of stakeholders involved in malaria control and prevention. Through the Ministry of Health and the NMCP, the government has established strategic collaborations with both research institutions and implementation partners, reflecting a sustained interest in advancing malaria control efforts through policy support and coordinated resource mobilization. Additionally, parliamentary committees such as the Tanzania Parliamentary Alliance Against Malaria (TAPAMA) have played a critical advocacy role, particularly at the municipal level. Their efforts have significantly contributed to maintaining malaria as a national health priority and fostering accountability and action across various levels of governance. Representative quotes: "There is what we call political will. The government considers malaria as something that is being addressed specially, and we have a National Malaria Control Program that is fully functional, and we are collaborating with other stakeholders like the National Institute of Medical Research and donors." — Male, 52, Malaria Program Manager "Medical Stores Department is sitting annually with the Ministry of Health, National Malaria Control Program (NMCP) and Non-Governmental Organizations to make a supply plan… government support is visible in how the National Malaria Control Program (NMCP) is embedded within the Ministry of Health." — Male, 47, Monitoring & Evaluation Officer "We also have a program under the National Institute of Medical Research in collaboration with Medicines for Malaria Venture to support the implementation of Multiple First-line treatment in Pwani… This shows the level of commitment stakeholders are putting into this." — Female, 45, Supply chain officer Training and Capacity Building A recurring concern from healthcare workers was the lack of exposure and training on alternative ACTs beyond ALU. Many participants pointed out that health personnel, particularly in rural or lower-level facilities, were unfamiliar with drugs like ASAQ and DPQ. This training gap, if not addressed, could hinder both prescribing behavior and patient education under MFT. Participants emphasized that continuous professional development and structured capacity-building programs are essential, particularly for frontline workers in both the public and private sectors. These programs should focus on proper diagnosis, understanding drug efficacy, pharmacovigilance, and patient counseling to ensure effective use of alternative ACTs. Representative quote: "The institution is always ready to receive, learn, and implement if it's going to benefit the patient. Pharmaceutical people are always in and out of the institutions giving information on new drugs, but formal training is still needed." __Female, 32 years, Medical Doctor "Training would help us. If I understand why this drug works better in some areas, I will confidently explain it to my patients and also prescribe it without fear." — Female, 54 years, Nurse Data-Driven Decision Making Data-driven decision-making is a cornerstone for the effective adoption of MFT for malaria treatment in Tanzania. Stakeholders emphasized that decisions to introduce alternative ACTs must be guided by robust evidence, including therapeutic efficacy studies, drug resistance surveillance, and treatment adherence data. These data sources help identify regional variations in resistance patterns and ensure that new therapies are deployed where they are most needed and will be most effective. Utilizing local and global research findings enhances policy formulation, strengthens accountability, and fosters stakeholder confidence. Institutions such as NMCP and NIMR play a critical role in analyzing and disseminating this evidence to inform strategic planning. By grounding decisions in real-world data, MFT implementation becomes more targeted, cost-effective, and sustainable across varying malaria transmission zones. Representative quotes: "You cannot just adopt based on conjecture. We must do extensive research to provide convincing evidence. That's why the government is conducting studies with partners like the National Institute of Medical Research, and the findings will guide our direction on which modality to use." — Male, 54 years, Program Manager "Policy change will follow research findings. Once we have concrete results from therapeutic efficacy studies, that's when we can begin implementing. It must be an evidence-based shift." — Female, 45 years, Supply chain officer "We'd better make changes depending on the research findings. Institutions like the National Institute of Medical Research and the Ifakara Health Institute will guide us on the best strategy. This is how we've always worked when it comes to malaria control." — Male, 47 years, Monitoring & Evaluation Officer Discussion To inform the design of this qualitative study, a desk review was conducted to assess the current landscape of malaria treatment and prevention strategies in Tanzania, particularly in the context of emerging artemisinin resistance. Data from the NMCP indicate notable progress in malaria control, with reductions in cases, mortality, and incidence across all age groups between 2020 and 2022. However, from 2022 to 2024, this decline plateaued, suggesting that existing strategies, primarily reliant on artemether-lumefantrine, may be insufficient to address the growing challenge of artemisinin resistance. This concern is particularly evident in regions like Kagera, where markers of resistance have been identified [7]. These findings highlight the need for innovative approaches, such as multiple first-line ACT therapies, to sustain malaria control efforts. Building on this context, the present study aimed to explore the barriers, facilitators, and strategies for adopting MFT for the management of uncomplicated malaria in Tanzania. Through in-depth interviews with key informants and healthcare providers, we aimed to elucidate the factors influencing the implementation of MFT in the Tanzanian context. The discussion is structured around three primary objectives: identifying barriers to MFT adoption, highlighting facilitators, and proposing actionable strategies to guide effective implementation. Our qualitative study explored the perspectives of various stakeholders involved in malaria prevention and control in Tanzania, shedding light on the opportunities and challenges associated with adopting MFT for uncomplicated malaria. We uncovered significant barriers—financial constraints, knowledge gaps, and logistical hurdles—facilitators such as robust government support and evidence-based decision-making, and strategies—driven decision-making and training, and capacity building. These findings illuminate the complex balance between MFT's potential to curb artemisinin resistance and the practical realities of implementation in resource-constrained settings. Here, we contextualize these results within the broader literature and propose actionable strategies to promote the adoption of MFT. Barriers to adopting MFT A major barrier to MFT adoption is the elevated cost of alternative ACTs, such as artesunate-amodiaquine (ASAQ) and DHP, compared to the widely used ALU. Uncertain funding from key donors, including the President's Malaria Initiative and the Global Fund, heightens concerns about MFT's financial viability [17]. This challenge echoes a modeling study that highlighted MFT's potential to delay resistance but underscored the upfront costs in low-resource settings [1]. Equally concerning are the limited knowledge and training among healthcare providers regarding alternative ACTs. Without adequate exposure or formal training, providers struggle to prescribe these therapies confidently or counsel patients effectively, which undermines treatment adherence and clinical outcomes [14]. These findings align with prior research in malaria-endemic regions, where insufficient training has consistently hindered the uptake of new treatment strategies [15]. Logistical and supply chain challenges further complicate the implementation of MFT. Tanzania's reliance on the MSD for ACT distribution, combined with bottlenecks in logistics and inadequate post-marketing surveillance, restricts the consistent availability of diverse ACTs. The centralized supply system and predominance of ALU in public health facilities run counter to MFT's foundational goal of ensuring multiple therapies to combat resistance [13]. Facilitators for adopting MFT On a more positive note, strong government commitment and stakeholder collaboration emerged as key facilitators. National treatment guidelines, Technical Working Groups (TWGs), and partnerships among the NMCP, MSD, National Institute for Medical Research (NIMR), and international allies demonstrate significant institutional resolve. Advocacy efforts, such as those led by the Tanzania Alliance for Patient Access to Medicines and Aids (TAPAMA), have elevated malaria control as a national priority, fostering a supportive policy environment for MFT [16]. Training and capacity building also stood out as vital facilitators. Stakeholders expressed enthusiasm for adopting MFT, provided they receive structured training on the efficacy, safety, and use of alternative ACTs, particularly for healthcare workers in peripheral facilities [14]. Moreover, data-driven decision-making, bolstered by NMCP and NIMR's therapeutic efficacy studies and resistance monitoring, ensures policies are grounded in robust evidence [7]. Strategies for effective MFT adoption To overcome these barriers, our study identified several effective strategies for implementing MFT. First, strengthening supply chains is critical. Improved forecasting, decentralized procurement, and better coordination between central and regional levels would ensure the availability of multiple ACTs across public and private sectors [13]. Second, a segmentation approach—tailoring ACTs to specific demographic or geographic groups—shows promise, particularly in areas with distinct resistance patterns, aligning with World Health Organization recommendations and modeling studies [18]. Third, sustained stakeholder engagement through awareness campaigns and inclusive planning can build ownership and drive behavioral change. Embedding MFT training within existing health programs could further institutionalize this approach [14]. Finally, strategic financial planning is essential. Cost-effectiveness analyses and innovative financing models could demonstrate MFT's long-term value, encouraging sustained donor commitment [17]. Study Limitations and Mitigation Strategies This study had several limitations. First, observer bias may have influenced the interpretation of the data. To minimize this, multiple researchers participated in coding and theme development, and member checking was performed during interviews to validate findings. Secondly, patients were not included as stakeholders in this study; therefore, other studies can explore patient perspectives towards adopting MFT in the management of uncomplicated malaria in Tanzania. Lastly, the study lacked a quantitative economic analysis of the strategy; therefore, cost-effectiveness analysis studies should be explored by other researchers. Conclusion This study shows that while Tanzania has reduced malaria cases in recent years, children under five remain disproportionately affected, with mortality showing slight improvement. The desk review highlighted fluctuations in malaria trends between 2020 and 2024, reflecting the fragility of current gains. Importation data revealed a heavy reliance on artemether–lumefantrine, which accounted for nearly three-quarters of imports from 2021 to 2025. In contrast, alternatives such as DHP were minimally available, indicating limited diversification. Qualitative findings identified systemic barriers to adopting MFT, including high costs, supply chain weaknesses, and limited provider training. At the same time, political commitment, growing use of surveillance and pharmacovigilance data, and provider willingness to adapt were important facilitators. MFT could help sustain ACT effectiveness and safeguard malaria outcomes, but requires deliberate policy action. Priorities include diversifying procurement, strengthening supply chains, securing sustainable financing, and building provider capacity. Future research should assess health system readiness, economic feasibility, and patient acceptability of MFT, with pilot implementation in high-burden regions to generate real-world evidence for national scale-up. Abbreviations ACT Artemisinin-based Combination Therapy ALU Artemether–Lumefantrine ASAQ Artesunate–Amodiaquine ATP Artesunate–Pyronaridine DHP Dihydroartemisinin–Piperaquine IRB Institutional Review Board KII Key Informant Interview MFT Multiple First-line Therapies MSD Medical Stores Department MUHAS Muhimbili University of Health and Allied Sciences NMCP National Malaria Control Programme PO-RALG President's Office – Regional Administration and Local Government RDT Rapid Diagnostic Test SP Sulfadoxine–Pyrimethamine SSA Sub-Saharan Africa TMDA Tanzania Medicines and Medical Devices Authority WHO World Health Organization. Declarations Ethical approval and consent to participate As the study involved human participants, ethical approval was obtained from the Institutional Ethical Review Board of the Muhimbili University of Health and Allied Sciences (MUHAS) (Ref: MUHAS-REC-03-2025-2739). Additionally, official permission was obtained to conduct interviews with personnel from the National Malaria Control Programme (NMCP), Medical Stores Department (MSD), President's Office – Regional Administration and Local Government (PO-RALG), and selected health facilities, in accordance with institutional requirements. The study was conducted in compliance with the Declaration of Helsinki on research involving human subjects, ensuring respect for participants' rights, protection of welfare, and maintenance of confidentiality. Informed consent was obtained electronically prior to participation. Participants were provided with detailed information about the study's purpose, procedures, potential risks, and benefits via email and Zoom briefing. Consent was documented verbally at the start of each recorded Zoom session. Participation was voluntary, and participants were reminded of their right to withdraw at any time without penalty or consequence. Confidentiality and anonymity were assured throughout the study. Authors Contributions HHN participated in conception, research design, data collection, data analysis and interpretation and drafting of the manuscript, GMB participated in conception, data analysis and interpretation, and revising the manuscript, RZS participated in designing the study and data analysis. AI participated in data analysis and manuscript writing. All authors read and approved the final version of this manuscript. Competing interests The authors declare that there are no competing interests. Consent to Publish Not Applicable Availability of Data Raw data analysed in this study are available from the corresponding author on reasonable request. Funding This study was funded by Muhimbili University of Health and Allied Sciences (MUHAS) and the Royal Society of Tropical Medicine and Hygiene (RSTMH). The funders had no role in the study design, data collection, data analysis, decision to publish or preparation of the manuscript. Acknowledgements The authors thank all participants who contributed their time and insights to this study. We are also grateful for the support received during data collection and analysis. References Malaria in Tanzania. Statistics & Facts | Severe Malaria Observatory [Internet]. [cited 2023 Apr 20]. Available from: https://www.severemalaria.org/countries/tanzania Ministry of Health (MoH) [Tanzania Mainland], Ministry of Health (MoH) [Zanzibar], National Bureau of Statistics (NBS), Office of the Chief Government Statistician (OCGS), and ICFMinistry of Health (MoH) [Tanzania Mainland], Ministry of Health (MoH) [Zanz and I. Tanzania Demographic and Health Survey and Malaria Indicator Survey 2022 Key Indicators Report. 2023;1–23. Moïse J, Kabor T, Siribi M, Hien D, Soulama I, Barry N et al. Feasibility and Acceptability of a Strategy Deploying Multiple First-Line Artemisinin-Based Combination Therapies for Uncomplicated Malaria in the Health District of Kaya, Burkina Faso. 2023. Ishengoma DS, Mandara CI, Bakari C, Fola AA, Madebe RA, Seth MD et al. Evidence of artemisinin partial resistance in northwestern Tanzania: clinical and molecular markers of resistance. Lancet Infect Dis. 2024. W.H.O. Strategy to respond to antimalarial drug resistance in Africa. Geneva: World Health Organization. 2022;102. Kaboré JMT, Siribié M, Hien D, Soulama I, Barry N, Nombré Y, et al. Attitudes, practices, and determinants of community care-seeking behaviours for fever/malaria episodes in the context of the implementation of multiple first-line therapies for uncomplicated malaria in the health district of Kaya, Burkina Faso. Malar J. 2022;21(1):1–14. Boni MF, White NJ, Baird JK. The Community As the Patient in Malaria-Endemic Areas: Preempting Drug Resistance with Multiple First-Line Therapies. PLoS Med. 2016;13(3):1–7. Boni MF, Smith DL, Laxminarayan R. Benefits of using multiple first-line therapies against malaria. Proc Natl Acad Sci U S A. 2008;105(37):14216–21. Global technical strategy for malaria, 2016–2030 [Internet]. Global Malaria Programme, World Health Organization., 2015 [cited 2024 Oct 7]. 29 p. Available from: https://www.who.int/docs/default-source/documents/global-technical-strategy-for-malaria-2016-2030.pdf#:~:text=Adopted%20by%20the%20World%20Health%20Assembly%20in%20May%202015,%20the Balikagala B, Fukuda N, Ikeda M, Katuro OT, Tachibana SI, Yamauchi M, et al. Evidence of Artemisinin-Resistant Malaria in Africa. N Engl J Med. 2021;385(13):1163–71. Uwimana A, Legrand E, Stokes BH, Ndikumana JLM, Warsame M, Umulisa N, et al. Emergence and clonal expansion of in vitro artemisinin-resistant Plasmodium falciparum kelch13 R561H mutant parasites in Rwanda. Nat Med. 2020;26(10):1602–8. Multiple first-line therapies. as part of the response to antimalarial drug resistance [Internet]. 2024 [cited 2025 Aug 23]. Available from: https://www.who.int/publications/i/item/9789240103603?utm Tanzania National Malaria Control Program. Malaria Diagnosis, Treatment and Preventive Therapies Guideline 2020 [Internet]. [cited 2024 Jan 28]. Available from: https://www.nmcp.go.tz/publication Braun V, Clarke V, Braun V, Clarke V. Using thematic analysis in psychology Using thematic analysis in psychology. Qualitative Research in Psychology ISSN: 2008;0887(2006). Edwards-Jones A. Qualitative data analysis with NVIVO. J Educ Teach. 2014;40(2):193–5. Turner SF, Cardinal LB, Burton RM. Research Design for Mixed Methods: A Triangulation-based Framework and Roadmap. Organ Res Methods. 2017;20(2):243–67. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 04 Dec, 2025 Read the published version in Malaria Journal → Version 1 posted Editorial decision: Revision requested 30 Oct, 2025 Reviews received at journal 29 Oct, 2025 Reviews received at journal 27 Oct, 2025 Reviews received at journal 18 Oct, 2025 Reviewers agreed at journal 14 Oct, 2025 Reviewers agreed at journal 14 Oct, 2025 Reviewers agreed at journal 13 Oct, 2025 Reviewers agreed at journal 12 Oct, 2025 Reviewers invited by journal 12 Oct, 2025 Editor assigned by journal 27 Sep, 2025 Submission checks completed at journal 27 Sep, 2025 First submitted to journal 25 Sep, 2025 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. 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10:49:13","extension":"xml","order_by":7,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":74635,"visible":true,"origin":"","legend":"","description":"","filename":"d850c651f458444091cf38fe54905a501structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7711744/v1/5e7ffe2628cb32e64b25ed36.xml"},{"id":92252128,"identity":"31e9ff92-5dc6-49d6-b867-a318885f048d","added_by":"auto","created_at":"2025-09-26 10:49:13","extension":"html","order_by":8,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":85842,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7711744/v1/d9291a723e7f642f10256fa9.html"},{"id":92252117,"identity":"fe73e952-8d64-46b5-b829-5764f2fcc055","added_by":"auto","created_at":"2025-09-26 10:49:13","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":46395,"visible":true,"origin":"","legend":"\u003cp\u003eProportions of imported antimalarial medicines in Tanzania, January 2021–July 2025\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7711744/v1/adb9674b2b80c78293b2ecbe.png"},{"id":92252119,"identity":"4d990102-ae31-49ad-874e-ad9a310ae08d","added_by":"auto","created_at":"2025-09-26 10:49:13","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":87544,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMalaria cases and deaths in Tanzania (2020–2024), disaggregated by all ages and children under five years.\u003c/strong\u003e The upper panel shows annual malaria cases, while the lower panel shows malaria deaths.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7711744/v1/995e2b8c11af87542d4ea341.png"},{"id":97724047,"identity":"dcb8870b-9f6d-4fd7-822d-b69e5a90a968","added_by":"auto","created_at":"2025-12-08 16:11:20","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1435821,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7711744/v1/0ab408fe-a2ac-47e9-a908-b014f0160b80.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Barriers and Facilitators to the Adoption of Multiple First-Line Therapies for Management of Uncomplicated Malaria in Tanzania: A Multi-Method Qualitative Study","fulltext":[{"header":"Background","content":"\u003cp\u003eMalaria is one of the diseases that has the highest number of cases and deaths globally. It accounts for 3% of cases and 4.1% of global deaths in 2020. In Tanzania, \u003cem\u003ePlasmodium falciparum\u003c/em\u003e is the primary causative agent of malaria, accounting for 96% of cases, while the remaining 4% are attributed to \u003cem\u003ePlasmodium vivax\u003c/em\u003e and \u003cem\u003ePlasmodium ovale\u003c/em\u003e. 93% of the Tanzanian population is at risk of malaria transmission, with children under the age of five years being the most affected group (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). The prevalence of malaria in children under five years differed across various regions, ranging from less than 1% in areas such as Zanzibar, Kilimanjaro, and Arusha to 20% in Mtwara and 23% in Tabora (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThe emergence of partial resistance of artemisinin derivatives and ACT partner drugs such as lumefantrine and piperaquine has recently emerged, especially in South East Asia, in countries like Cambodia (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). In Africa, partial resistance has been observed in Rwanda and Uganda, characterized by delayed parasite clearance and an increase in treatment failure. A molecular surveillance study conducted in Tanzania revealed the presence of the artemisinin resistance marker kelch13 (k13), specifically therg561His mutation, in the Kagera region (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Parasites harboring this mutation have an advantage under the current regimen due to their high transmissibility and improved parasite fitness (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eDue to the risk of artemisinin resistance spreading to sub-Saharan Africa, malaria control strategies must be adjusted by optimizing current ACT therapy. The simultaneous use of multiple artemisinin-based malaria combinations has been suggested (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). For example, in the year 1990, mefloquine resistance, a drug co-formulated with ACT, was observed in Thailand and Myanmar, which manifested as slow parasite clearance (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eMany countries' national policies recommend the use of a single first-line therapy for most clinical cases in the management of uncomplicated malaria, despite the availability of many drugs to manage malaria. This \"wait and switch\" process tends to overwhelm public healthcare systems, leading to increased morbidity and mortality 8). For example, the Tanzania standard treatment guideline recommends the use of artemether-lumefantrine (ALU) as the first-line treatment and dihydroartemisinin-piperaquine (DHP) in cases where ALU isn't effective or contraindicated. No other drug is listed in the guidelines apart from these two that can be used in the management of uncomplicated malaria in Tanzania. With the possibility of developing alternative drugs being unlikely for ACTs in the short term, it is essential to preserve the therapeutic lifespan of available ACTs.\u003c/p\u003e\u003cp\u003eThe WHO Global Technical Strategy for Malaria 2016\u0026ndash;2030 recommends formulating strategies that take into account the epidemiology and heterogeneity of malaria in the country (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). This can be achieved by dividing the country into different strata and implementing targeted interventions within those stratified groups. For example, a particular region could employ a specific ACT combination, while another region uses a different combination.\u003c/p\u003e\u003cp\u003eMultiple first-line treatment (MFT) is defined as a drug policy in which several therapies are made available for clinicians to choose by clinicians to manage uncomplicated malaria in a society. This strategy can be implemented in various ways, including segmentation and rotation. The segmentation approach aims to stratify the ACT market into distinct age groups, including pediatrics, pregnant women, and adults, by geographical regions. The rotation approach seeks to switch the ACT regimen after a specific period by monitoring the efficacy of the currently available medications. The drugs are made available in both private and public health facilities.\u003c/p\u003e\u003cp\u003eIn various studies, it has been demonstrated that employing multiple first-line strategies offers several benefits, including slowing down the evolution of resistance by increasing the variability of drugs in the parasite's environment and a reduction in overall selection pressure for resistance to that particular drug (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Offering multiple first-line therapies not only allows for flexibility in treating patients with specific needs or drug sensitivities but also helps distribute selective pressure across different drugs, thereby slowing the development of resistance. Moreover, having a range of effective first-line options strengthens healthcare systems by providing more adaptable, regionally tailored responses to malaria, which is crucial for sustainable control and eradication efforts. Adopting multiple treatments thus ensures more resilient, accessible, and effective malaria care, particularly in resource-limited settings that face high disease burdens. However, only ALU is widely used as a first-line treatment in many endemic areas, limiting insights into the practical application of alternative regimens.\u003c/p\u003e\u003cp\u003eTherefore, this study aimed to examine the barriers to adopting a broader range of first-line treatments, as well as the facilitators that could enable their integration into case management of uncomplicated malaria in Tanzania.\u003c/p\u003e"},{"header":"Study design, period and population","content":"\u003cp\u003eA multi-method qualitative study was undertaken between April and June 2025 to explore the barriers, facilitators, and strategies for adopting MFT for uncomplicated malaria in Tanzania. The study combined a desk review of epidemiological and pharmaceutical data with key informant and in-depth interviews. This design allowed for the integration of documentary evidence with stakeholder perspectives to ensure contextual relevance.\u003c/p\u003e\u003cp\u003eThe desk review was conducted to provide epidemiological and pharmaceutical context for the qualitative enquiry. National Malaria Control Programme (NMCP) data, covering the period from January 2020 to December 2024, were analyzed to assess malaria trends, including annual cases, deaths, and the under-five burden. These data were disaggregated by age group (\u0026lt;\u0026thinsp;5 years versus \u0026ge;\u0026thinsp;5 years) and analysed using descriptive statistics and simple trend tests to identify temporal patterns. Additionally, secondary data on antimalarial imports between January 2021 and July 2025 were obtained from the Tanzania Medicines and Medical Devices Authority (TMDA). The desk review served two purposes: (i) to provide a descriptive overview of the malaria burden and treatment landscape in Tanzania, and (ii) to guide the design and interpretation of the qualitative interviews by highlighting priority gaps and contextual drivers.\u003c/p\u003e\u003cp\u003eSemi-structured interviews were conducted with purposively selected participants from the domains of malaria policy, regulation, supply chain, and healthcare delivery. Eligibility criteria included a minimum of 12 months' experience in malaria case management, health policy, or pharmaceutical logistics. Participants were drawn from both the public and private sectors, including policymakers, regulatory officials, supply chain managers, and frontline healthcare providers (doctors, nurses, and pharmacists).\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eSample size and sampling techniques\u003c/h2\u003e\u003cp\u003eThe study planned 10 key informant interviews (KIIs) with stakeholders, including policymakers and implementers, and five in-depth interviews (IDIs) with healthcare workers (doctors, pharmacists, and nurses) from hospitals in Dar es Salaam and Dodoma. Participants were purposively selected based on expertise in malaria case management. KIIs were chosen to capture diverse institutional perspectives on MFT, while IDIs provided insights from frontline healthcare workers. Interviews continued until data saturation was reached, ensuring credibility and completeness.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eData collection procedures\u003c/h3\u003e\n\u003cp\u003eSemi-structured interview guides were developed in English and translated into Kiswahili to ensure clarity, inclusivity, and ease of expression for participants. Kiswahili, being the national language, allowed respondents to communicate freely and provide richer, more detailed insights without language barriers. The guides contained open-ended questions to explore barriers, facilitators, and strategies for adopting a multi-first-line treatment strategy for malaria in Tanzania. They were developed deductively from study objectives, literature (\u003cspan additionalcitationids=\"CR11 CR12\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e), desk review, and expert input, and refined as new issues emerged. KIIs and IDIs were conducted in informants' offices at convenient times. Each interview lasted 30\u0026ndash;60 minutes and was facilitated by a researcher with support from a co-researcher who took notes and audio recordings. Verbal and non-verbal responses were captured, and debriefings were held after each session to ensure quality and identify emerging issues.\u003c/p\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003eData analysis\u003c/h2\u003e\u003cp\u003eDescriptive statistics were used to summarize malaria cases, deaths, and patterns of antimalarial importation. Annual malaria case counts and deaths were disaggregated by age group (\u0026lt;\u0026thinsp;5 years vs. \u0026ge;5 years) and presented both as absolute numbers and proportions of the national burden. Trends from 2020 to 2024 were visualized using line and bar graphs. Comparisons of malaria burden between children under five years and individuals aged five years and above were assessed using the Chi-square test for independence. Temporal trends in the proportion of cases and deaths attributed to under-fives between 2020 and 2024 were examined using Pearson's correlation as an approximation of a trend test. To evaluate the change in under-five mortality between 2022 and 2023, a two-proportion z-test was applied. Statistical significance was set at \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05. All quantitative analyses were conducted using R software.\u003c/p\u003e\u003cp\u003eQualitative data from KIIs and IDIs were analyzed using inductive thematic analysis guided by Braun and Clarke's framework (2006) (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). This approach enabled themes to emerge directly from the data, while addressing the study objectives of identifying barriers, facilitators, and strategies for adopting MFT for malaria treatment.\u003c/p\u003e\u003cp\u003e All interviews were conducted via Zoom due to logistical constraints, audio-recorded with participants' consent, and transcribed verbatim in Kiswahili to ensure clarity, openness, and cultural relevance. Field notes were incorporated to enrich contextual detail. Coding and theme development were performed in Kiswahili to preserve meaning, and only representative quotes and final themes were translated into English for reporting. Using NVivo software (version 15), coding was undertaken independently by two researchers, followed by the development of a shared codebook in which categories were consolidated into overarching themes and subthemes.\u003c/p\u003e\u003cp\u003eData collection and analysis were conducted concurrently until thematic saturation was achieved. Rigor was maintained through triangulation, peer debriefing, and reflexive discussions (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). Credibility was strengthened through purposive sampling and the use of Kiswahili, which allowed for the capture of richer narratives. Dependability was achieved by adhering to standardized guides, while confirmability was supported through detailed documentation and reflexivity. Transferability was ensured by providing comprehensive descriptions of the study setting, participants, and procedures.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003eDesk Review Findings\u003c/h2\u003e\u003cdiv id=\"Sec8\" class=\"Section3\"\u003e\u003ch2\u003eAntimalarials Importation in Tanzania (January 2021 - July 2025)\u003c/h2\u003e\u003cp\u003eALU dominated the market, accounting for 73.5% of all imports, followed by artesunate (12%), artemether (6%), and SP (4.9%). Smaller shares were recorded for DHP (2.6%) and Quinine (0.9%), while other medicines (primaquine, atovaquone\u0026thinsp;+\u0026thinsp;proguanil, and hydroxychloroquine) together accounted for less than 0.5% (Fig.\u0026nbsp;1).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\n\u003ch3\u003eMalaria Cases and Deaths in Tanzania (January 2020 – December 2024)\u003c/h3\u003e\n\u003cp\u003eBetween 2020 and 2024, under-five children consistently bore a disproportionate malaria burden compared to older age groups, with differences in both cases and deaths highly significant (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Analysis of temporal trends showed that the proportion of cases among under-fives declined significantly over time (p\u0026thinsp;=\u0026thinsp;0.011), while the proportion of deaths in this age group showed no significant change (p\u0026thinsp;=\u0026thinsp;0.802). Although the number of under-five malaria deaths increased between 2022 and 2023, this rise was not statistically significant (p\u0026thinsp;=\u0026thinsp;0.159)(Fig.\u0026nbsp;2\u003cb\u003e).\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\n\u003ch3\u003eQualitative Findings\u003c/h3\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eDescription of data collection activities\u003c/h2\u003e\u003cp\u003eA total of 12 qualitative interviews were conducted with various stakeholders between April and June. These consisted of six key informant interviews and six in-depth interviews. The interviews consisted of a diverse group of stakeholders, including healthcare providers, regulatory officials, policy formulators, and supply chain personnel. The KIIs involved interviewing key personnel from the NMCP, the President's Office - Regional Administration and Local Government (PO-RALG), and the Medical Stores Department (MSD). The in-depth interviews (IDIs) involved interviewing healthcare workers, including medical doctors, pharmacists, and nurses. The average duration of the IDIs was 23 minutes, with the shortest one lasting 15 minutes and the longest one lasting 39 minutes. The KII's duration ranged from 24 to 37 minutes, resulting in an average of 31 minutes. These interviews took longer due to individual expertise and the vast amount of information they provided during the interviews.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003eInterviewed participants' characteristics\u003c/h2\u003e\u003cp\u003eThe study involved twelve (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e) participants recruited from a broad spectrum of health institutions across Tanzania, including regional referral hospitals and prominent government agencies such as the NMCP and the MSD. Participants' ages ranged from 29 to 54 years, with a median age of 38 years. The gender distribution was relatively balanced, with a slight predominance of female participants.\u003c/p\u003e\u003cp\u003eThe participants represented diverse professional backgrounds, including medical doctors, nurses, pharmacists, policy analysts, and supply chain specialists. This professional heterogeneity facilitated the inclusion of multiple stakeholder perspectives pertinent to malaria case management. On average, participants had six (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) years of professional experience, indicating substantial exposure to health service delivery systems. Respondents were drawn from both public and private healthcare settings, including institutions such as Bugando and Singida Regional Referral Hospitals, the Aga Khan Hospital, and key government offices. This institutional diversity enabled the study to capture insights from both clinical and policy implementation contexts.\u003c/p\u003e\u003cp\u003eThe educational level of participants was evenly distributed between those with bachelor's degrees (n\u0026thinsp;=\u0026thinsp;6) and master's degrees (n\u0026thinsp;=\u0026thinsp;6), reflecting a high level of technical expertise and academic engagement. The variation in educational backgrounds contributed to the analytical richness and credibility of the study's findings, particularly regarding the feasibility and adoption of multiple first-line therapies for malaria management in Tanzania (\u003cb\u003eTable\u0026nbsp;1\u003c/b\u003e).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003eEmerging themes from qualitative analysis\u003c/h2\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eThemes and sub-themes emerged from qualitative interviews\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eThemes\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSub-themes\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCost and financial barriers\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026bull; High cost of alternative therapies\u003c/p\u003e\u003cp\u003e\u0026bull; Inadequate NHIF coverage\u003c/p\u003e\u003cp\u003e\u0026bull; Donor dependency and financial instability\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eKnowledge and training gaps\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026bull; Familiarity and preference for ALU\u003c/p\u003e\u003cp\u003e\u0026bull; Social misconceptions about alternatives\u003c/p\u003e\u003cp\u003e\u0026bull; Weak STG implementation at lower levels\u003c/p\u003e\u003cp\u003e\u0026bull; Poor adherence and understanding at the patient level\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSupply chain and logistics barriers\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026bull; Unreliable drug supply and logistics\u003c/p\u003e\u003cp\u003e\u0026bull; Inadequate data for decision-making\u003c/p\u003e\u003cp\u003e\u0026bull; Unavailability of medicines\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGovernment and stakeholders' commitment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026bull; Existence of national guidelines and TWGs\u003c/p\u003e\u003cp\u003e\u0026bull; Political will and institutional commitment\u003c/p\u003e\u003cp\u003e\u0026bull; Technical studies supporting MFT\u003c/p\u003e\u003cp\u003e\u0026bull; Stakeholder engagement and coordination\u003c/p\u003e\u003cp\u003e\u0026bull; Phased rollout and implementation\u003c/p\u003e\u003cp\u003e\u0026bull; There's a transition guideline that shows clearly the steps to adopt new therapies.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTraining and capacity building\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026bull; Training and capacity building\u003c/p\u003e\u003cp\u003e\u0026bull; Social behavior changes communication (SBCC)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eData-driven decision making\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026bull; Data-driven policy and procurement\u003c/p\u003e\u003cp\u003e\u0026bull; Engagement of research institutions\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\u003ch2\u003eBarriers to MFT adoption\u003c/h2\u003e\u003cdiv id=\"Sec15\" class=\"Section3\"\u003e\u003ch2\u003eCost and financial barriers\u003c/h2\u003e\u003cp\u003eThe cost of alternative ACTs, other than ALU, has been identified as a significant barrier to implementing MFT strategies for the management of uncomplicated malaria in Tanzania, both at the individual and national levels.\u003c/p\u003e\u003cp\u003eAt the individual level, ACTs such as DHP are considerably more expensive, with costs ranging from three to four times that of ALU.\u003c/p\u003e\u003cp\u003eAt the national level, ALU benefits from government subsidies, whereas alternative therapies do not. Compounding the challenge, several key donors\u0026mdash;most notably the President's Malaria Initiative (PMI)\u0026mdash;have begun withdrawing support for malaria programs. This shift highlights the potential financial constraints Tanzania may face if it adopts an MFT approach.\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv id=\"Sec16\" class=\"Section2\"\u003e\u003ch2\u003eRepresentative quotes:\u003c/h2\u003e\u003cp\u003e\u003cem\u003e\"A single dose of Dihydroartemisinin-piperaquine is approximately four times the unit cost of Artemether-Lumefantrine\".\u003c/em\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec17\" class=\"Section2\"\u003e\u003ch2\u003e__Male, 54 years, Program Manager\u003c/h2\u003e\u003cp\u003e\u003cem\u003e\"Funders like the President's Malaria Initiative have pulled back, and we're not sure if the Global Fund will continue supporting us. These setbacks have slowed down progress toward adopting Multiple First-line Treatment.\"\u003c/em\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec18\" class=\"Section2\"\u003e\u003ch2\u003e__Female, 45 years, Supply chain officer\u003c/h2\u003e\u003cp\u003e\u003cem\u003e\"We rely on the Global Fund to procure Artemether Lumefantrine \u0026ndash; without it, sustainability is a concern.\"\u003c/em\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec19\" class=\"Section2\"\u003e\u003ch2\u003e__Female, 47 years, Malaria Unit Head\u003c/h2\u003e\u003cdiv id=\"Sec20\" class=\"Section3\"\u003e\u003ch2\u003eKnowledge and training gaps\u003c/h2\u003e\u003cp\u003e It was observed that many healthcare workers possessed limited knowledge and had received minimal training on ACTs other than ALU and DHP, which are the most commonly used and recommended in the Standard Treatment Guidelines and National Essential Medicines List (STG-NEMLIT). This knowledge gap presents a major obstacle to the successful adoption of MFT strategies. When healthcare providers are unfamiliar with alternative therapies, they are unlikely to prescribe or procure them for use in their facilities.\u003c/p\u003e\u003cp\u003eAt the patient level, limited awareness and understanding of proper adherence to antimalarial medications\u0026mdash;particularly after discharge\u0026mdash;further compounds the challenge. Without sufficient patient education, the introduction of new therapies may lead to poor adherence, ultimately undermining the effectiveness of MFT implementation.\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv id=\"Sec21\" class=\"Section2\"\u003e\u003ch2\u003eRepresentative quotes:\u003c/h2\u003e\u003cp\u003e\u003cem\u003e\"Most of us have never handled Artesunate Amodiaquine or Dihydroartemisinin Piperaquine. We only know Artemether Lumefantrine, so exposure and proper instruction are critical.\"\u003c/em\u003e\u003c/p\u003e\u003cdiv id=\"Sec22\" class=\"Section3\"\u003e\u003ch2\u003e__Male, 32 years, Medical Doctor\u003c/h2\u003e\u003cp\u003e\u003cem\u003e\"Sometimes patients don't return or don't understand the importance of completing the dose, and that compromises adherence.\"\u003c/em\u003e\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv id=\"Sec23\" class=\"Section2\"\u003e\u003ch2\u003e__Female, 51 years, Nurse\u003c/h2\u003e\u003cp\u003e\u003cem\u003e\"When healthcare providers are only trained on a single treatment regimen like Artemether Lumefantrine, they tend to hesitate or feel unsure about using other available Artemisinin Combination Therapies. Without proper training on alternatives, it becomes difficult to adopt new treatment strategies.\"\u003c/em\u003e\u003c/p\u003e\u003cdiv id=\"Sec24\" class=\"Section3\"\u003e\u003ch2\u003e__Male, 34 years, Monitoring \u0026amp; Evaluation Officer\u003c/h2\u003e\u003cdiv id=\"Sec25\" class=\"Section4\"\u003e\u003ch2\u003eSupply chain and logistics barriers\u003c/h2\u003e\u003cp\u003eSupply chain and logistical challenges were widely cited as significant barriers to implementing MFT for uncomplicated malaria in Tanzania. Government health facilities depend heavily on the MSD for drug supply, yet MSD often distributes only one type of ACT, which is ALU. This practice not only limits treatment options but also contradicts the principle of MFT, which requires the simultaneous availability of multiple therapies.\u003c/p\u003e\u003cp\u003eAdditionally, delays in drug distribution, limited forecasting capacity, and poor coordination among stakeholders also contribute to the logistical complexity. Inadequate infrastructure, transportation issues, and the absence of robust systems for post-marketing surveillance further exacerbate these barriers.\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv id=\"Sec26\" class=\"Section3\"\u003e\u003ch2\u003eRepresentative quotes:\u003c/h2\u003e\u003cp\u003e\u003cem\u003e\"We distribute based on quantified demand \u0026ndash; switching drugs means recalibrating logistics.\"\u003c/em\u003e\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv id=\"Sec27\" class=\"Section2\"\u003e\u003ch2\u003e__Female, 31 years, Supply chain officer\u003c/h2\u003e\u003cp\u003e\u003cem\u003e\"We rely on the Medical Stores Department for drug supplies. Sometimes, they stock one drug type for months, and then it runs out. That defeats the purpose of having options.\"\u003c/em\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec28\" class=\"Section2\"\u003e\u003ch2\u003e__Male, 35 years, Hospital Pharmacist\u003c/h2\u003e\u003cp\u003e\u003cem\u003e\"The biggest issue is the supply and logistics system\u0026mdash;it relies heavily on a single supplier.\"\u003c/em\u003e\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003e— Male, 32 years, Medical Doctor\u003c/h3\u003e\n\u003cp\u003e\u003cem\u003e\"We are not directly involved in procurement processes. We rely on the Medical Stores Department and the central level to ensure availability.\"\u003c/em\u003e\u003c/p\u003e\u003cdiv id=\"Sec30\" class=\"Section2\"\u003e\u003ch2\u003e__Female, 47 years, Malaria Unit Head\u003c/h2\u003e\u003cdiv id=\"Sec31\" class=\"Section3\"\u003e\u003ch2\u003eFacilitators and Strategies to MFT adoption\u003c/h2\u003e\u003cdiv id=\"Sec32\" class=\"Section4\"\u003e\u003ch2\u003eGovernment and stakeholders' commitment\u003c/h2\u003e\u003cp\u003eThe Government of Tanzania has demonstrated strong political commitment toward malaria eradication, as evidenced by its active engagement with a wide range of stakeholders involved in malaria control and prevention. Through the Ministry of Health and the NMCP, the government has established strategic collaborations with both research institutions and implementation partners, reflecting a sustained interest in advancing malaria control efforts through policy support and coordinated resource mobilization.\u003c/p\u003e\u003cp\u003eAdditionally, parliamentary committees such as the Tanzania Parliamentary Alliance Against Malaria (TAPAMA) have played a critical advocacy role, particularly at the municipal level. Their efforts have significantly contributed to maintaining malaria as a national health priority and fostering accountability and action across various levels of governance.\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv id=\"Sec33\" class=\"Section3\"\u003e\u003ch2\u003eRepresentative quotes:\u003c/h2\u003e\u003cp\u003e\u003cem\u003e\"There is what we call political will. The government considers malaria as something that is being addressed specially, and we have a National Malaria Control Program that is fully functional, and we are collaborating with other stakeholders like the National Institute of Medical Research and donors.\"\u003c/em\u003e\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\n\u003ch3\u003e— Male, 52, Malaria Program Manager\u003c/h3\u003e\n\u003cp\u003e\u003cem\u003e\"Medical Stores Department is sitting annually with the Ministry of Health, National Malaria Control Program (NMCP) and Non-Governmental Organizations to make a supply plan\u0026hellip; government support is visible in how the National Malaria Control Program (NMCP) is embedded within the Ministry of Health.\"\u003c/em\u003e\u003c/p\u003e\n\u003ch3\u003e— Male, 47, Monitoring \u0026 Evaluation Officer\u003c/h3\u003e\n\u003cp\u003e\u003cem\u003e\"We also have a program under the National Institute of Medical Research in collaboration with Medicines for Malaria Venture to support the implementation of Multiple First-line treatment in Pwani\u0026hellip; This shows the level of commitment stakeholders are putting into this.\"\u003c/em\u003e\u003c/p\u003e\u003cdiv id=\"Sec36\" class=\"Section2\"\u003e\u003ch2\u003e\u0026mdash; Female, 45, Supply chain officer\u003c/h2\u003e\u003cdiv id=\"Sec37\" class=\"Section3\"\u003e\u003ch2\u003eTraining and Capacity Building\u003c/h2\u003e\u003cp\u003eA recurring concern from healthcare workers was the lack of exposure and training on alternative ACTs beyond ALU. Many participants pointed out that health personnel, particularly in rural or lower-level facilities, were unfamiliar with drugs like ASAQ and DPQ. This training gap, if not addressed, could hinder both prescribing behavior and patient education under MFT.\u003c/p\u003e\u003cp\u003eParticipants emphasized that continuous professional development and structured capacity-building programs are essential, particularly for frontline workers in both the public and private sectors. These programs should focus on proper diagnosis, understanding drug efficacy, pharmacovigilance, and patient counseling to ensure effective use of alternative ACTs.\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv id=\"Sec38\" class=\"Section2\"\u003e\u003ch2\u003eRepresentative quote:\u003c/h2\u003e\u003cp\u003e\u003cem\u003e\"The institution is always ready to receive, learn, and implement if it's going to benefit the patient. Pharmaceutical people are always in and out of the institutions giving information on new drugs, but formal training is still needed.\"\u003c/em\u003e\u003c/p\u003e\u003cdiv id=\"Sec39\" class=\"Section3\"\u003e\u003ch2\u003e__Female, 32 years, Medical Doctor\u003c/h2\u003e\u003cp\u003e\u003cem\u003e\"Training would help us. If I understand why this drug works better in some areas, I will confidently explain it to my patients and also prescribe it without fear.\"\u003c/em\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e\u0026mdash; Female, 54 years, Nurse\u003c/b\u003e\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\n\u003ch3\u003eData-Driven Decision Making\u003c/h3\u003e\n\u003cp\u003eData-driven decision-making is a cornerstone for the effective adoption of MFT for malaria treatment in Tanzania. Stakeholders emphasized that decisions to introduce alternative ACTs must be guided by robust evidence, including therapeutic efficacy studies, drug resistance surveillance, and treatment adherence data. These data sources help identify regional variations in resistance patterns and ensure that new therapies are deployed where they are most needed and will be most effective.\u003c/p\u003e\u003cp\u003eUtilizing local and global research findings enhances policy formulation, strengthens accountability, and fosters stakeholder confidence. Institutions such as NMCP and NIMR play a critical role in analyzing and disseminating this evidence to inform strategic planning. By grounding decisions in real-world data, MFT implementation becomes more targeted, cost-effective, and sustainable across varying malaria transmission zones.\u003c/p\u003e\n\u003ch3\u003eRepresentative quotes:\u003c/h3\u003e\n\u003cp\u003e\u003cem\u003e\"You cannot just adopt based on conjecture. We must do extensive research to provide convincing evidence. That's why the government is conducting studies with partners like the National Institute of Medical Research, and the findings will guide our direction on which modality to use.\"\u003c/em\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e\u0026mdash; Male, 54 years, Program Manager\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003e\"Policy change will follow research findings. Once we have concrete results from therapeutic efficacy studies, that's when we can begin implementing. It must be an evidence-based shift.\"\u003c/em\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e\u0026mdash; Female, 45 years, Supply chain officer\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003e\"We'd better make changes depending on the research findings. Institutions like the National Institute of Medical Research and the Ifakara Health Institute will guide us on the best strategy. This is how we've always worked when it comes to malaria control.\"\u003c/em\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e\u0026mdash; Male, 47 years, Monitoring \u0026amp; Evaluation Officer\u003c/b\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eTo inform the design of this qualitative study, a desk review was conducted to assess the current landscape of malaria treatment and prevention strategies in Tanzania, particularly in the context of emerging artemisinin resistance. Data from the NMCP indicate notable progress in malaria control, with reductions in cases, mortality, and incidence across all age groups between 2020 and 2022. However, from 2022 to 2024, this decline plateaued, suggesting that existing strategies, primarily reliant on artemether-lumefantrine, may be insufficient to address the growing challenge of artemisinin resistance. This concern is particularly evident in regions like Kagera, where markers of resistance have been identified [7]. These findings highlight the need for innovative approaches, such as multiple first-line ACT therapies, to sustain malaria control efforts.\u003c/p\u003e\u003cp\u003eBuilding on this context, the present study aimed to explore the barriers, facilitators, and strategies for adopting MFT for the management of uncomplicated malaria in Tanzania. Through in-depth interviews with key informants and healthcare providers, we aimed to elucidate the factors influencing the implementation of MFT in the Tanzanian context. The discussion is structured around three primary objectives: identifying barriers to MFT adoption, highlighting facilitators, and proposing actionable strategies to guide effective implementation.\u003c/p\u003e\u003cp\u003eOur qualitative study explored the perspectives of various stakeholders involved in malaria prevention and control in Tanzania, shedding light on the opportunities and challenges associated with adopting MFT for uncomplicated malaria. We uncovered significant barriers\u0026mdash;financial constraints, knowledge gaps, and logistical hurdles\u0026mdash;facilitators such as robust government support and evidence-based decision-making, and strategies\u0026mdash;driven decision-making and training, and capacity building. These findings illuminate the complex balance between MFT's potential to curb artemisinin resistance and the practical realities of implementation in resource-constrained settings. Here, we contextualize these results within the broader literature and propose actionable strategies to promote the adoption of MFT.\u003c/p\u003e\n\u003ch3\u003eBarriers to adopting MFT\u003c/h3\u003e\n\u003cp\u003eA major barrier to MFT adoption is the elevated cost of alternative ACTs, such as artesunate-amodiaquine (ASAQ) and DHP, compared to the widely used ALU. Uncertain funding from key donors, including the President's Malaria Initiative and the Global Fund, heightens concerns about MFT's financial viability [17]. This challenge echoes a modeling study that highlighted MFT's potential to delay resistance but underscored the upfront costs in low-resource settings [1]. Equally concerning are the limited knowledge and training among healthcare providers regarding alternative ACTs. Without adequate exposure or formal training, providers struggle to prescribe these therapies confidently or counsel patients effectively, which undermines treatment adherence and clinical outcomes [14]. These findings align with prior research in malaria-endemic regions, where insufficient training has consistently hindered the uptake of new treatment strategies [15].\u003c/p\u003e\u003cp\u003eLogistical and supply chain challenges further complicate the implementation of MFT. Tanzania's reliance on the MSD for ACT distribution, combined with bottlenecks in logistics and inadequate post-marketing surveillance, restricts the consistent availability of diverse ACTs. The centralized supply system and predominance of ALU in public health facilities run counter to MFT's foundational goal of ensuring multiple therapies to combat resistance [13].\u003c/p\u003e\n\u003ch3\u003eFacilitators for adopting MFT\u003c/h3\u003e\n\u003cp\u003eOn a more positive note, strong government commitment and stakeholder collaboration emerged as key facilitators. National treatment guidelines, Technical Working Groups (TWGs), and partnerships among the NMCP, MSD, National Institute for Medical Research (NIMR), and international allies demonstrate significant institutional resolve. Advocacy efforts, such as those led by the Tanzania Alliance for Patient Access to Medicines and Aids (TAPAMA), have elevated malaria control as a national priority, fostering a supportive policy environment for MFT [16]. Training and capacity building also stood out as vital facilitators. Stakeholders expressed enthusiasm for adopting MFT, provided they receive structured training on the efficacy, safety, and use of alternative ACTs, particularly for healthcare workers in peripheral facilities [14]. Moreover, data-driven decision-making, bolstered by NMCP and NIMR's therapeutic efficacy studies and resistance monitoring, ensures policies are grounded in robust evidence [7].\u003c/p\u003e\n\u003ch3\u003eStrategies for effective MFT adoption\u003c/h3\u003e\n\u003cp\u003eTo overcome these barriers, our study identified several effective strategies for implementing MFT. First, strengthening supply chains is critical. Improved forecasting, decentralized procurement, and better coordination between central and regional levels would ensure the availability of multiple ACTs across public and private sectors [13]. Second, a segmentation approach\u0026mdash;tailoring ACTs to specific demographic or geographic groups\u0026mdash;shows promise, particularly in areas with distinct resistance patterns, aligning with World Health Organization recommendations and modeling studies [18]. Third, sustained stakeholder engagement through awareness campaigns and inclusive planning can build ownership and drive behavioral change. Embedding MFT training within existing health programs could further institutionalize this approach [14]. Finally, strategic financial planning is essential. Cost-effectiveness analyses and innovative financing models could demonstrate MFT's long-term value, encouraging sustained donor commitment [17].\u003c/p\u003e\n\u003ch3\u003eStudy Limitations and Mitigation Strategies\u003c/h3\u003e\n\u003cp\u003eThis study had several limitations. First, observer bias may have influenced the interpretation of the data. To minimize this, multiple researchers participated in coding and theme development, and member checking was performed during interviews to validate findings.\u003c/p\u003e\u003cp\u003eSecondly, patients were not included as stakeholders in this study; therefore, other studies can explore patient perspectives towards adopting MFT in the management of uncomplicated malaria in Tanzania.\u003c/p\u003e\u003cp\u003eLastly, the study lacked a quantitative economic analysis of the strategy; therefore, cost-effectiveness analysis studies should be explored by other researchers.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study shows that while Tanzania has reduced malaria cases in recent years, children under five remain disproportionately affected, with mortality showing slight improvement. The desk review highlighted fluctuations in malaria trends between 2020 and 2024, reflecting the fragility of current gains. Importation data revealed a heavy reliance on artemether\u0026ndash;lumefantrine, which accounted for nearly three-quarters of imports from 2021 to 2025. In contrast, alternatives such as DHP were minimally available, indicating limited diversification. Qualitative findings identified systemic barriers to adopting MFT, including high costs, supply chain weaknesses, and limited provider training. At the same time, political commitment, growing use of surveillance and pharmacovigilance data, and provider willingness to adapt were important facilitators. MFT could help sustain ACT effectiveness and safeguard malaria outcomes, but requires deliberate policy action. Priorities include diversifying procurement, strengthening supply chains, securing sustainable financing, and building provider capacity. Future research should assess health system readiness, economic feasibility, and patient acceptability of MFT, with pilot implementation in high-burden regions to generate real-world evidence for national scale-up.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003e\u003cb\u003eACT\u003c/b\u003e\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eArtemisinin-based Combination Therapy\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003e\u003cb\u003eALU\u003c/b\u003e\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eArtemether\u0026ndash;Lumefantrine\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003e\u003cb\u003eASAQ\u003c/b\u003e\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eArtesunate\u0026ndash;Amodiaquine\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003e\u003cb\u003eATP\u003c/b\u003e\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eArtesunate\u0026ndash;Pyronaridine\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003e\u003cb\u003eDHP\u003c/b\u003e\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eDihydroartemisinin\u0026ndash;Piperaquine\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003e\u003cb\u003eIRB\u003c/b\u003e\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eInstitutional Review Board\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003e\u003cb\u003eKII\u003c/b\u003e\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eKey Informant Interview\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003e\u003cb\u003eMFT\u003c/b\u003e\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eMultiple First-line Therapies\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003e\u003cb\u003eMSD\u003c/b\u003e\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eMedical Stores Department\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003e\u003cb\u003eMUHAS\u003c/b\u003e\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eMuhimbili University of Health and Allied Sciences\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003e\u003cb\u003eNMCP\u003c/b\u003e\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eNational Malaria Control Programme\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003e\u003cb\u003ePO-RALG\u003c/b\u003e\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ePresident's Office \u0026ndash; Regional Administration and Local Government\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003e\u003cb\u003eRDT\u003c/b\u003e\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eRapid Diagnostic Test\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003e\u003cb\u003eSP\u003c/b\u003e\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eSulfadoxine\u0026ndash;Pyrimethamine\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003e\u003cb\u003eSSA\u003c/b\u003e\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eSub-Saharan Africa\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003e\u003cb\u003eTMDA\u003c/b\u003e\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eTanzania Medicines and Medical Devices Authority\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003e\u003cb\u003eWHO\u003c/b\u003e\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eWorld Health Organization.\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAs the study involved human participants, ethical approval was obtained from the Institutional Ethical Review Board of the Muhimbili University of Health and Allied Sciences (MUHAS) (Ref: MUHAS-REC-03-2025-2739). Additionally, official permission was obtained to conduct interviews with personnel from the National Malaria Control Programme (NMCP), Medical Stores Department (MSD), President\u0026apos;s Office \u0026ndash; Regional Administration and Local Government (PO-RALG), and selected health facilities, in accordance with institutional requirements. The study was conducted in compliance with the Declaration of Helsinki on research involving human subjects, ensuring respect for participants\u0026apos; rights, protection of welfare, and maintenance of confidentiality. Informed consent was obtained electronically prior to participation. Participants were provided with detailed information about the study\u0026apos;s purpose, procedures, potential risks, and benefits via email and Zoom briefing. Consent was documented verbally at the start of each recorded Zoom session. Participation was voluntary, and participants were reminded of their right to withdraw at any time without penalty or consequence. Confidentiality and anonymity were assured throughout the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHHN participated in conception, research design, data collection, data analysis and interpretation and drafting of the manuscript, GMB participated in conception, data analysis and interpretation, and revising the manuscript, RZS participated in designing the study and data analysis. AI participated in data analysis and manuscript writing. All authors read and approved the final version of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that there are no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Publish\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot Applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of Data\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRaw data analysed in this study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was funded by Muhimbili University of Health and Allied Sciences (MUHAS) and the Royal Society of Tropical Medicine and Hygiene (RSTMH). The funders had no role in the study design, data collection, data analysis, decision to publish or preparation of the manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank all participants who contributed their time and insights to this study. We are also grateful for the support received during data collection and analysis.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMalaria in Tanzania. Statistics \u0026amp; Facts | Severe Malaria Observatory [Internet]. [cited 2023 Apr 20]. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.severemalaria.org/countries/tanzania\u003c/span\u003e\u003cspan address=\"https://www.severemalaria.org/countries/tanzania\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMinistry of Health (MoH) [Tanzania Mainland], Ministry of Health (MoH) [Zanzibar], National Bureau of Statistics (NBS), Office of the Chief Government Statistician (OCGS), and ICFMinistry of Health (MoH) [Tanzania Mainland], Ministry of Health (MoH) [Zanz and I. Tanzania Demographic and Health Survey and Malaria Indicator Survey 2022 Key Indicators Report. 2023;1\u0026ndash;23.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMo\u0026iuml;se J, Kabor T, Siribi M, Hien D, Soulama I, Barry N et al. Feasibility and Acceptability of a Strategy Deploying Multiple First-Line Artemisinin-Based Combination Therapies for Uncomplicated Malaria in the Health District of Kaya, Burkina Faso. 2023.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eIshengoma DS, Mandara CI, Bakari C, Fola AA, Madebe RA, Seth MD et al. Evidence of artemisinin partial resistance in northwestern Tanzania: clinical and molecular markers of resistance. Lancet Infect Dis. 2024.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eW.H.O. Strategy to respond to antimalarial drug resistance in Africa. Geneva: World Health Organization. 2022;102.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKabor\u0026eacute; JMT, Siribi\u0026eacute; M, Hien D, Soulama I, Barry N, Nombr\u0026eacute; Y, et al. Attitudes, practices, and determinants of community care-seeking behaviours for fever/malaria episodes in the context of the implementation of multiple first-line therapies for uncomplicated malaria in the health district of Kaya, Burkina Faso. Malar J. 2022;21(1):1\u0026ndash;14.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBoni MF, White NJ, Baird JK. The Community As the Patient in Malaria-Endemic Areas: Preempting Drug Resistance with Multiple First-Line Therapies. PLoS Med. 2016;13(3):1\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBoni MF, Smith DL, Laxminarayan R. Benefits of using multiple first-line therapies against malaria. Proc Natl Acad Sci U S A. 2008;105(37):14216\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGlobal technical strategy for malaria, 2016\u0026ndash;2030 [Internet]. Global Malaria Programme, World Health Organization., 2015 [cited 2024 Oct 7]. 29 p. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.who.int/docs/default-source/documents/global-technical-strategy-for-malaria-2016-2030.pdf#:~:text=Adopted%20by%20the%20World%20Health%20Assembly%20in%20May%202015,%20the\u003c/span\u003e\u003cspan address=\"https://www.who.int/docs/default-source/documents/global-technical-strategy-for-malaria-2016-2030.pdf#:~:text=Adopted%20by%20the%20World%20Health%20Assembly%20in%20May%202015,%20the\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBalikagala B, Fukuda N, Ikeda M, Katuro OT, Tachibana SI, Yamauchi M, et al. Evidence of Artemisinin-Resistant Malaria in Africa. N Engl J Med. 2021;385(13):1163\u0026ndash;71.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eUwimana A, Legrand E, Stokes BH, Ndikumana JLM, Warsame M, Umulisa N, et al. Emergence and clonal expansion of in vitro artemisinin-resistant Plasmodium falciparum kelch13 R561H mutant parasites in Rwanda. Nat Med. 2020;26(10):1602\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMultiple first-line therapies. as part of the response to antimalarial drug resistance [Internet]. 2024 [cited 2025 Aug 23]. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.who.int/publications/i/item/9789240103603?utm\u003c/span\u003e\u003cspan address=\"https://www.who.int/publications/i/item/9789240103603?utm\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTanzania National Malaria Control Program. Malaria Diagnosis, Treatment and Preventive Therapies Guideline 2020 [Internet]. [cited 2024 Jan 28]. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.nmcp.go.tz/publication\u003c/span\u003e\u003cspan address=\"https://www.nmcp.go.tz/publication\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBraun V, Clarke V, Braun V, Clarke V. Using thematic analysis in psychology Using thematic analysis in psychology. Qualitative Research in Psychology ISSN: 2008;0887(2006).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eEdwards-Jones A. Qualitative data analysis with NVIVO. J Educ Teach. 2014;40(2):193\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTurner SF, Cardinal LB, Burton RM. Research Design for Mixed Methods: A Triangulation-based Framework and Roadmap. Organ Res Methods. 2017;20(2):243\u0026ndash;67.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"malaria-journal","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"malj","sideBox":"Learn more about [Malaria Journal](http://malariajournal.biomedcentral.com/)","snPcode":"12936","submissionUrl":"https://submission.nature.com/new-submission/12936/3","title":"Malaria Journal","twitterHandle":"@malariajournal","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Malaria, Antimalarials, Multiple-fist line treatment, Tanzania","lastPublishedDoi":"10.21203/rs.3.rs-7711744/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7711744/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eMalaria remains a major public health burden in Tanzania, where \u003cem\u003ePlasmodium falciparum\u003c/em\u003e accounts for 96% of infections and children under five years experience the highest mortality. The emergence of \u003cem\u003ekelch13\u003c/em\u003e mutations and partial resistance to artemisinin derivatives poses a threat to the sustainability of artemisinin-based combination therapies (ACTs). Reliance on artemether–lumefantrine (ALU) as the dominant first-line treatment increases selective pressure. The World Health Organization recommends multiple first-line therapies (MFT) to slow the development of resistance. This study examined the barriers, facilitators, and potential strategies for adopting MFT for uncomplicated malaria in Tanzania.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eA multi-method qualitative study was conducted. A desk review of national malaria data (2020–2024) was conducted to examine trends in incidence, mortality, and treatment outcomes. Data on importation from the national medicine regulatory authority (2021–2025) were analyzed to assess the ACT importation pattern. The desk review provided epidemiological and pharmaceutical context for qualitative enquiry. Semi-structured interviews were conducted with purposively selected participants, including policymakers, regulators, supply chain managers, and frontline healthcare providers. Interviews were transcribed and thematically analyzed using Braun and Clarke's framework with NVivo software.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eBetween 2020 and 2024, malaria cases declined from approximately 8.9 million to 7.2 million before resurging to 8.1 million in 2023; deaths followed a similar trend. Children under five consistently bore a higher burden, representing 34% of all cases and 46% of deaths. While case incidence in this age group declined significantly (p=0.011), mortality showed no improvement (p=0.802). Importation data revealed ALU comprised 73.5% of all antimalarial imports, compared to 12% for artesunate, 6% for artemether, and only 2.6% for dihydroartemisinin–piperaquine, highlighting limited diversification. Qualitative findings identified barriers, including the high cost of alternative artemisinin-based combination therapies (ACTs), limited provider training, and weak supply chains. Facilitators, on the other hand, demonstrated a strong political commitment, engaged in capacity-building initiatives, and relied on therapeutic efficacy and pharmacovigilance data to inform their approach.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eMFT presents a promising strategy for prolonging ACT efficacy and enhancing malaria case management in Tanzania. However, financial constraints, import dependence on ALU, and inadequate provider preparedness limit implementation. Successful adoption will require diversification of ACT imports, strengthening supply chains, sustained capacity-building, and embedding surveillance and regulatory data into policy decision-making.\u003c/p\u003e","manuscriptTitle":"Barriers and Facilitators to the Adoption of Multiple First-Line Therapies for Management of Uncomplicated Malaria in Tanzania: A Multi-Method Qualitative Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-26 10:49:08","doi":"10.21203/rs.3.rs-7711744/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-10-30T09:20:52+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-29T14:32:40+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-28T03:13:16+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-18T18:40:47+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"70099938517774317523103737199740464903","date":"2025-10-14T15:32:37+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"209395359434151665043138882376483152734","date":"2025-10-14T09:56:31+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"134870898576982932422832789964133527912","date":"2025-10-13T05:57:12+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"90002769379916380673054250107161923359","date":"2025-10-12T09:51:09+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-10-12T08:51:13+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-09-27T18:18:51+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-09-27T18:17:58+00:00","index":"","fulltext":""},{"type":"submitted","content":"Malaria Journal","date":"2025-09-25T10:12:52+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"malaria-journal","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"malj","sideBox":"Learn more about [Malaria Journal](http://malariajournal.biomedcentral.com/)","snPcode":"12936","submissionUrl":"https://submission.nature.com/new-submission/12936/3","title":"Malaria Journal","twitterHandle":"@malariajournal","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"0fca2bbf-5a77-4fee-9626-e162899e60db","owner":[],"postedDate":"September 26th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-12-08T16:05:59+00:00","versionOfRecord":{"articleIdentity":"rs-7711744","link":"https://doi.org/10.1186/s12936-025-05710-1","journal":{"identity":"malaria-journal","isVorOnly":false,"title":"Malaria Journal"},"publishedOn":"2025-12-04 15:57:13","publishedOnDateReadable":"December 4th, 2025"},"versionCreatedAt":"2025-09-26 10:49:08","video":"","vorDoi":"10.1186/s12936-025-05710-1","vorDoiUrl":"https://doi.org/10.1186/s12936-025-05710-1","workflowStages":[]},"version":"v1","identity":"rs-7711744","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7711744","identity":"rs-7711744","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}