Malaria Stratification Mapping in Thailand to Support Prevention of Reestablishment.

Thailand aims to eliminate malaria by 2026, with 46 of the country's 77 provinces already verified as malaria free. However, these provinces remain susceptible to the reestablishment of indigenous transmission that would threaten the national goal. Thus, the country is prioritizing national and subnational prevention of reestablishment (POR) planning while considering the spatial heterogeneity of the remaining malaria caseload. To support POR efforts, a novel nonmodeling method produced a malaria stratification map at the tambon (subdistrict) level, incorporating malaria case data, demographic data, and environmental factors. The stratification analysis categorized 7,425 tambons into the following four risk strata: Local Transmission (2.9%), At Risk for Transmission (3.1%), High Risk for Reintroduction (2.9%), and Low Risk for Reintroduction (91.1%). The stratification map will support the national program to target malaria interventions in remaining hotspots and mitigate the risk of transmission in malaria-free areas.

The contribution of active case detection to malaria elimination in Thailand.

INTRODUCTION: Thailand's malaria surveillance system complements passive case detection with active case detection (ACD), comprising proactive ACD (PACD) methods and reactive ACD (RACD) methods that target community members near index cases. However, it is unclear if these resource-intensive surveillance strategies continue to provide useful yield. This study aimed to document the evolution of the ACD programme and to assess the potential to optimise PACD and RACD. METHODS: This study used routine data from all 6 292 302 patients tested for malaria from fiscal year 2015 (FY15) to FY21. To assess trends over time and geography, ACD yield was defined as the proportion of cases detected among total screenings. To investigate geographical variation in yield from FY17 to FY21, we used intercept-only generalised linear regression models (binomial distribution), allowing random intercepts at different geographical levels. A costing analysis gathered the incremental financial costs for one instance of ACD per focus. RESULTS: Test positivity for ACD was low (0.08%) and declined over time (from 0.14% to 0.03%), compared with 3.81% for passive case detection (5.62%-1.93%). Whereas PACD and RACD contributed nearly equal proportions of confirmed cases in FY15, by FY21 PACD represented just 32.37% of ACD cases, with 0.01% test positivity. Each geography showed different yields. We provide a calculator for PACD costs, which vary widely. RACD costs an expected US$226 per case investigation survey (US$1.62 per person tested) or US$461 per mass blood survey (US$1.10 per person tested). CONCLUSION: ACD yield, particularly for PACD, is waning alongside incidence, offering an opportunity to optimise. PACD may remain useful only in specific microcontexts with sharper targeting and implementation. RACD could be narrowed by defining demographic-based screening criteria rather than geographical based. Ultimately, ACD can continue to contribute to Thailand's malaria elimination programme but with more deliberate targeting to balance operational costs.

Assessing the acceptability and feasibility of reactive drug administration for malaria elimination in a Plasmodium vivax predominant setting: a qualitative study in two provinces in Thailand.

BACKGROUND: Reactive case detection (RACD) or testing and treatment of close contacts of recent malaria cases, is commonly practiced in settings approaching malaria elimination, but standard diagnostics have limited sensitivity to detect low level infections. Reactive drug administration (RDA), or presumptive treatment without testing, is an alternative approach, but better understanding regarding community acceptability and operational feasibility are needed. METHODS: A qualitative study was conducted as part of a two-arm cluster randomized-controlled trial evaluating the effectiveness of RDA targeting high-risk villages and forest workers for reducing Plasmodium vivax and P. falciparum malaria in Thailand. Key informant interviews (KIIs) and focus group discussions (FGDs) were conducted virtually among key public health staff, village health volunteers (VHVs), and household members that implemented or received RDA activities. Transcriptions were reviewed, coded, and managed manually using Dedoose qualitative data analysis software, then underwent qualitative content analysis to identify key themes. RESULTS: RDA was well accepted by household members and public health staff that implemented it. RDA participation was driven by fear of contracting malaria, eagerness to receive protection provided by malaria medicines, and the increased access to health care. Concerns were raised about the safety of taking malaria medicines without having an illness, particularly if underlying health conditions existed. Health promotion hospital (HPH) staff implementing RDA noted its operational feasibility, but highlighted difficulty in traveling to remote areas, and requested additional travel resources and hiring more VHVs. Other challenges were highlighted including the need for additional training for VHVs on malaria activities and the inability of HPH staff to conduct RDA due to other health priorities (e.g., Covid-19). More training and practice for VHVs were noted as ways to improve implementation of RDA. CONCLUSIONS: To maximize uptake of RDA, regular education and sensitization campaigns in collaboration with village leaders on the purpose and rationale of RDA will be critical. To alleviate safety concerns and increase participant safety, a rigorous pharmacovigilance program will be important. To accelerate uptake of RDA, trust between HPH staff and VHVs and the communities they serve must continue to be strengthened to ensure acceptance of the intervention. TRIAL REGISTRATION: This study was approved by the Committee on Human Research at the University of California San Francisco (19-28,060) and the local Ethics Committee for Research in Human Subjects at Tak Provincial Health office (009/63) and Kanchanaburi Provincial health office (Kor Chor 0032.002/2185). Local authorities and health officers in the provinces, districts, and villages agreed upon and coordinated the implementation of the study. All methods in this study were carried out in accordance with relevant guidelines and regulations.

Assessing Thailand's 1-3-7 surveillance strategy in accelerating malaria elimination.

BACKGROUND: Thailand's strong malaria elimination programme relies on effective implementation of its 1-3-7 surveillance strategy, which was endorsed and implemented nationwide in 2016. For each confirmed malaria patient, the Ministry of Public Health's Division of Vector Borne Diseases (DVBD) ensures completion of case notification within 1 day, case investigation within 3 days, and foci investigation within 7 days. To date, there has not been a comprehensive assessment of the performance and achievements of the 1-3-7 surveillance strategy although such results could help Thailand's future malaria elimination strategic planning. METHODS: This study examined adherence to the 1-3-7 protocols, tracked progress against set targets, and examined geographic variations in implementation of the 1-3-7 strategy in the programme's initial 5 years. An auto-regressive integrated moving average (ARIMA) time series analysis with seasonal decomposition assessed the plausible implementation effect of the 1-3-7 strategy on malaria incidence in the programme's initial 5 years. The quantitative analysis included all confirmed malaria cases from public health and non-governmental community facilities from October 2014 to September 2021 (fiscal year [FY] 2015 to FY 2021) (n = 77,405). The spatial analysis included active foci with known geocoordinates that reported more than five cases from FY 2018 to FY 2021. RESULTS: From FY 2017 to FY 2021, on-time case notification improved from 24.4% to 89.3%, case investigations from 58.0% to 96.5%, and foci investigations from 37.9% to 87.2%. Adherence to timeliness protocols did not show statistically significant variation by area risk classification. However, adherence to 1-3-7 protocols showed a marked spatial heterogeneity among active foci, and the ARIMA model showed a statistically significant acceleration in the reduction of malaria incidence. The 1-3-7 strategy national indicators and targets in Thailand have shown progressive success, and most targets were achieved for FY 2021. CONCLUSION: The results of Thailand's 1-3-7 surveillance strategy are associated with a decreased incidence in the period following the adoption of the strategy although there is notable geographic variation. The DVBD will continue to implement and adapt the 1-3-7 strategy to accelerate progress toward malaria elimination. This assessment may be useful for domestic strategic planning and to other countries considering more intensive case and foci investigation and response strategies.

Progress and challenges of integrated drug efficacy surveillance for uncomplicated malaria in Thailand.

BACKGROUND: Integrated drug efficacy surveillance (iDES) was formally introduced nationally across Thailand in fiscal year 2018 (FY2018), building on a history of drug efficacy monitoring and interventions. According to the National Malaria Elimination Strategy for Thailand 2017-2026, diagnosis is microscopically confirmed, treatment is prescribed, and patients are followed up four times to ensure cure. METHODS: Routine patient data were extracted from the malaria information system for FY2018-FY2020. Treatment failure of first-line therapy was defined as confirmed parasite reappearance within 42 days for Plasmodium falciparum and 28 days for Plasmodium vivax. The primary outcome was the crude drug efficacy rate, estimated using Kaplan-Meier methods, at day 42 for P. falciparum treated with dihydroartemisinin-piperaquine plus primaquine, and day 28 for P. vivax treated with chloroquine plus primaquine; day 60 and day 90 efficacy were secondary outcomes for P. vivax. RESULTS: The proportion of patients with outcomes recorded at day 42 for P. falciparum malaria and at day 28 for P. vivax malaria has been increasing, with FY2020 follow-up rates of 61.5% and 57.2%, respectively. For P. falciparum malaria, day 42 efficacy in FY2018 was 92.4% (n = 249), in FY2019 93.3% (n = 379), and in FY2020 98.0% (n = 167). Plasmodium falciparum recurrences occurred disproportionally in Sisaket Province, with day 42 efficacy rates of 75.9% in FY2018 (n = 59) and 49.4% in FY2019 (n = 49), leading to an update in first-line therapy to pyronaridine-artesunate at the provincial level, rolled out in FY2020. For P. vivax malaria, day 28 efficacy (chloroquine efficacy) was 98.5% in FY2018 (n = 2048), 99.1% in FY2019 (n = 2206), and 99.9% in FY2020 (n = 2448), and day 90 efficacy (primaquine efficacy) was 94.8%, 96.3%, and 97.1%, respectively. CONCLUSIONS: In Thailand, iDES provided operationally relevant data on drug efficacy, enabling the rapid amendment of treatment guidelines to improve patient outcomes and reduce the potential for the spread of drug-resistant parasites. A strong case-based surveillance system, integration with other health system processes, supporting biomarker collection and molecular analyses, and cross-border collaboration may maximize the potential of iDES in countries moving towards elimination.

Implementation and success factors from Thailand's 1-3-7 surveillance strategy for malaria elimination.

Thailand's National Malaria Elimination Strategy 2017-2026 introduced the 1-3-7 strategy as a robust surveillance and response approach for elimination that would prioritize timely, evidence-based action. Under this strategy, cases are reported within 1 day, cases are investigated within 3 days, and foci are investigated and responded to within 7 days, building on Thailand's long history of conducting case investigation since the 1980s. However, the hallmark of the 1-3-7 strategy is timeliness, with strict deadlines for reporting and response to accelerate elimination. This paper outlines Thailand's experience adapting and implementing the 1-3-7 strategy, including success factors such as a cross-sectoral Steering Committee, participation in a collaborative regional partnership, and flexible local budgets. The programme continues to evolve to ensure prompt and high-quality case management, capacity maintenance, and adequate supply of lifesaving commodities based on surveillance data. Results from implementation suggest the 1-3-7 strategy has contributed to Thailand's decline in malaria burden; this experience may be useful for other countries aiming to eliminate malaria.

A foci cohort analysis to monitor successful and persistent foci under Thailand's Malaria Elimination Strategy.

BACKGROUND: Thailand's success in reducing malaria burden is built on the efficient "1-3-7" strategy applied to the surveillance system. The strategy is based on rapid case notification within 1 day, case investigation within 3 days, and targeted foci response to reduce the spread of Plasmodium spp. within 7 days. Autochthonous transmission is still occurring in the country, threatening the goal of reaching malaria-free status by 2024. This study aimed to assess the effectiveness of the 1-3-7 strategy and identify factors associated with presence of active foci. METHODS: Data from the national malaria information system were extracted from fiscal years 2013 to 2019; after data cleaning, the final dataset included 81,012 foci. A Cox's proportional hazards model was built to investigate factors linked with the probability of becoming an active focus from 2015 to 2019 among foci that changed status from non-active to active focus during the study period. We performed a model selection technique based on the Akaike Information Criteria (AIC). RESULTS: The number of yearly active foci decreased from 2227 to 2013 to 700 in 2019 (68.5 %), and the number of autochthonous cases declined from 17,553 to 3,787 (78.4 %). The best Cox's hazard model showed that foci in which vector control interventions were required were 18 % more likely to become an active focus. Increasing compliance with the 1-3-7 strategy had a protective effect, with a 22 % risk reduction among foci with over 80 % adherence to 1-3-7 timeliness protocols. Other factors associated with likelihood to become or remain an active focus include previous classification as an active focus, presence of Plasmodium falciparum infections, level of forest disturbance, and location in border provinces. CONCLUSIONS: These results identified factors that favored regression of non-active foci to active foci during the study period. The model and relative risk map align with the national malaria program's district stratification and shows strong spatial heterogeneity, with high probability to record active foci in border provinces. The results of the study may be useful for honing Thailand's program to eliminate malaria and for other countries aiming to accelerate malaria elimination.

The Evolution of the Malaria Clinic: The Cornerstone of Malaria Elimination in Thailand.

Background: Malaria Clinics (MCs) have served communities in Thailand since 1965 and are still playing a critical role in providing early diagnosis and effective treatment of malaria. Methods: We reviewed six decades of published manuscripts, articles, strategies, and plans regarding MC operations in Thailand;,and analyzed national program surveillance data in both malaria control and malaria elimination phases. Results: MCs accounted for 39.8% of malaria tests and 54.8% of positive cases by the end of the 1980s. The highest number of MCs established was 544 in 1997. MCs contributed to 6.7% of all tests and 30% of all positive cases over the 2015-2017 period. Between 2017 and June 2019, during the malaria elimination phase, MCs continued to test an average of 67% of all persons tested for malaria, and confirmed 38.3% of all positive cases detected in the country. Conclusions: Testing and positive rates of MCs are on a gradual decline as the overall burden of malaria declines annually, which may reflect decreasing transmission intensity. Although the number of MCs in the last three years has been stable (n = 240), the attrition of MC staff poses a real challenge to the longevity of MCs in the absence of a human resource plan to support the elimination phase. It is necessary to identify and support capacity gaps and needs as MCs are absorbed into an integrated and decentralized program, while ensuring that the Division of Vector Borne Diseases (DVBD) maintains its necessary technical and advisory role.

The Investment Case for Malaria Elimination in Thailand: A Cost-Benefit Analysis.

After a dramatic decline in the annual malaria incidence in Thailand since 2000, the Thai government developed a National Malaria Elimination Strategy (NMES) to end local malaria transmission by 2024. This study examines the expected costs and benefits of funding the NMES (elimination scenario) versus not funding malaria elimination programming (resurgence scenario) from 2017 to 2036. Two case projection approaches were used to measure the number of malaria cases over the study period, combined with a set of Thailand-specific economic assumptions, to evaluate the cost of a malaria case and to quantify the cost-benefit ratio of elimination. Model A projects cases based on national historical case data using a log-normal regression and change-point analysis model. Model B projects cases based on periodic Yala Province-level outbreak cycles and incorporating NMES political and programmatic goals. In the base case, both models predict that elimination would prevent 1.86-3.11 million malaria cases from 2017 to 2036, with full NMES implementation proving to be cost-saving in all models, perspectives, and scenarios, except for the health system-only perspective in the Model A base case and all perspectives in the Model A worst case. From the societal perspective, every 1 US dollars (US$) spent on the NMES would-depending on case projections used-potentially result in a considerable return on investment, ranging from US$ 2 to US$ 15. Although the two case projection approaches resulted in different cost-benefit ratios, both models showed cost savings and suggest that ending local malaria transmission in Thailand would yield a positive return on investment.

Implementation of G6PD testing and primaquine for P. vivax radical cure: Operational perspectives from Thailand and Cambodia.

Following progressive success in reducing the burden of malaria over the past two decades, countries of the Asia Pacific are now aiming for elimination of malaria by 2030. Plasmodium falciparum and Plasmodium vivax are the two main malaria species that are endemic in the region. P. vivax is generally perceived to be less severe but will be harder to eliminate, owing partly to its dormant liver stage (known as a hypnozoite) that can cause multiple relapses following an initial clinical episode caused by a mosquito-borne infection. Primaquine is the only anti-hypnozoite drug against P. vivax relapse currently available, with tafenoquine in the pipeline. However, both drugs may cause severe haemolysis in individuals with deficiency of the enzyme glucose-6-phosphate dehydrogenase (G6PD), a hereditary defect. The overall incidence of malaria has significantly declined in both Thailand and Cambodia over the last 15 years. However, P. vivax has replaced P. falciparum as the dominant species in large parts of both countries. This paper presents the experience of the national malaria control programmes of the two countries, in their efforts to implement safe primaquine therapy for the radical cure, i.e. relapse prevention, of P. vivax malaria by introducing a rapid, point-of-care test to screen for G6PD deficiency.

Challenges for achieving safe and effective radical cure of Plasmodium vivax: a round table discussion of the APMEN Vivax Working Group.

The delivery of safe and effective radical cure for Plasmodium vivax is one of the greatest challenges for achieving malaria elimination from the Asia-Pacific by 2030. During the annual meeting of the Asia Pacific Malaria Elimination Network Vivax Working Group in October 2016, a round table discussion was held to discuss the programmatic issues hindering the widespread use of primaquine (PQ) radical cure. Participants included 73 representatives from 16 partner countries and 33 institutional partners and other research institutes. In this meeting report, the key discussion points are presented and grouped into five themes: (i) current barriers for glucose-6-phosphate deficiency (G6PD) testing prior to PQ radical cure, (ii) necessary properties of G6PD tests for wide scale deployment, (iii) the promotion of G6PD testing, (iv) improving adherence to PQ regimens and (v) the challenges for future tafenoquine (TQ) roll out. Robust point of care (PoC) G6PD tests are needed, which are suitable and cost-effective for clinical settings with limited infrastructure. An affordable and competitive test price is needed, accompanied by sustainable funding for the product with appropriate training of healthcare staff, and robust quality control and assurance processes. In the absence of quantitative PoC G6PD tests, G6PD status can be gauged with qualitative diagnostics, however none of the available tests is currently sensitive enough to guide TQ treatment. TQ introduction will require overcoming additional challenges including the management of severely and intermediately G6PD deficient individuals. Robust strategies are needed to ensure that effective treatment practices can be deployed widely, and these should ensure that the caveats are outweighed by  the benefits of radical cure for both the patients and the community. Widespread access to quality controlled G6PD testing will be critical.

Active case detection with pooled real-time PCR to eliminate malaria in Trat province, Thailand.

We conducted contact tracing and high-risk group screening using pooled real-time polymerase chain reaction (PCR) to support malaria elimination in Thailand. PCR detected more Plasmodium infections than the local and expert microscopists. High-throughput pooling technique reduced costs and allowed prompt reporting of results.