Environmental Factors Linked to Reporting of Active Malaria Foci in Thailand.

Thailand has made substantial progress towards malaria elimination, with 46 of the country's 77 provinces declared malaria-free as part of the subnational verification program. Nonetheless, these areas remain vulnerable to the reintroduction of malaria parasites and the reestablishment of indigenous transmission. As such, prevention of reestablishment (POR) planning is of increasing concern to ensure timely response to increasing cases. A thorough understanding of both the risk of parasite importation and receptivity for transmission is essential for successful POR planning. Routine geolocated case- and foci-level epidemiological and case-level demographic data were extracted from Thailand's national malaria information system for all active foci from October 2012 to September 2020. A spatial analysis examined environmental and climate factors associated with the remaining active foci. A logistic regression model collated surveillance data with remote sensing data to investigate associations with the probability of having reported an indigenous case within the previous year. Active foci are highly concentrated along international borders, particularly Thailand's western border with Myanmar. Although there is heterogeneity in the habitats surrounding active foci, land covered by tropical forest and plantation was significantly higher for active foci than other foci. The regression results showed that tropical forest, plantations, forest disturbance, distance from international borders, historical foci classification, percentage of males, and percentage of short-term residents were associated with the high probability of reporting indigenous cases. These results confirm that Thailand's emphasis on border areas and forest-going populations is well placed. The results suggest that environmental factors alone are not driving malaria transmission in Thailand; rather, other factors, including demographics and behaviors that intersect with exophagic vectors, may also be contributors. However, these factors are syndemic, so human activities in areas covered by tropical forests and plantations may result in malaria importation and, potentially, local transmission, in foci that had previously been cleared. These factors should be addressed in POR planning.

Leveraging geo-referenced malaria information to increase domestic financial support for malaria elimination in Thailand.

Thailand's National Malaria Elimination Strategy 2017-2026 seeks to increase domestic support and financing for malaria elimination. During 2018-2020, through a series of training sessions, public health officials in Thailand utilized foci-level malaria data to engage subdistrict-level government units known as Local Administrative Organizations (LAOs) with the aim of increasing their understanding of their local malaria situation, collaboration with public health networks, and advocacy for financial support of targeted interventions in villages within their jurisdictions. As a result of these efforts, total LAO funding support for malaria nearly doubled from the 2017 baseline to 2020. In 2021, a novel "LAO collaboration" feature was added to Thailand's national malaria information system that enables tracking and visualization of LAO financial support of malaria in areas with transmission, by year, down to the subdistrict level. This case study describes Thailand's experience implementing the LAO engagement strategy, quantifying and monitoring the financial support mobilized from LAOs, and results from a qualitative study in five high-performance provinces examining factors and approaches that foster successful local collaboration between LAOs, public health networks, and communities for malaria prevention and response. Results from the study showed that significant malaria endemicity or local outbreaks helped spur collaboration in multiple provinces. Increases in LAO support and involvement were attributable to four approaches employed by public health officials: (a) strengthening malaria literacy and response capacity of LAOs, (b) organizational leadership in response to outbreaks, (c) utilization of structural incentives, and (d) multisectoral involvement in malaria response. In two provinces, capacity building of LAOs in malaria vector control, following a precedent set by Thailand's dengue programme, enabled LAO personnel to play both funding and implementation roles in local malaria response. Wider replication of the LAO engagement strategy across Thailand may sustain gains and yield efficiencies in the fight against malaria as the vector-borne disease workforce declines. Lessons from Thailand's experience may be useful for malaria programmes in other geographies to support the goals and sustainability of elimination and prevention of re-establishment by improving financing through local collaboration between the health system and elected officials.

Civilian-military malaria outbreak response in Thailand: an example of multi-stakeholder engagement for malaria elimination.

BACKGROUND: In April 2017, the Thai Ministry of Public Health (MoPH) was alerted to a potential malaria outbreak among civilians and military personnel in Sisaket Province, a highly forested area bordering Cambodia. The objective of this study was to present findings from the joint civilian-military outbreak response. METHODS: A mixed-methods approach was used to assess risk factors among cases reported during the 2017 Sisaket malaria outbreak. Routine malaria surveillance data from January 2013 to March 2018 obtained from public and military medical reporting systems and key informant interviews (KIIs) (n = 72) were used to develop hypotheses about potential factors contributing to the outbreak. Joint civilian-military response activities included entomological surveys, mass screen and treat (MSAT) and vector control campaigns, and scale-up of the "1-3-7" reactive case detection approach among civilians alongside a pilot "1-3-7" study conducted by the Royal Thai Army (RTA). RESULTS: Between May-July 2017, the monthly number of MoPH-reported cases surpassed the epidemic threshold. Outbreak cases detected through the MoPH mainly consisted of Thai males (87%), working as rubber tappers (62%) or military/border police (15%), and Plasmodium vivax infections (73%). Compared to cases from the previous year (May-July 2016), outbreak cases were more likely to be rubber tappers (OR = 14.89 [95% CI: 5.79-38.29]; p < 0.001) and infected with P. vivax (OR=2.32 [1.27-4.22]; p = 0.006). Themes from KIIs were congruent with findings from routine surveillance data. Though limited risk factor information was available from military cases, findings from RTA's "1-3-7" study indicated transmission was likely occurring outside military bases. Data from entomological surveys and MSAT campaigns support this hypothesis, as vectors were mostly exophagic and parasite prevalence from MSAT campaigns was very low (range: 0-0.7% by PCR/microscopy). CONCLUSIONS: In 2017, an outbreak of mainly P. vivax occurred in Sisaket Province, affecting mainly military and rubber tappers. Vector control use was limited to the home/military barracks, indicating that additional interventions were needed during high-risk forest travel periods. Importantly, this outbreak catalyzed joint civilian-military collaborations and integration of the RTA into the national malaria elimination strategy (NMES). The Sisaket outbreak response serves as an example of how civilian and military public health systems can collaborate to advance national malaria elimination goals in Southeast Asia and beyond.

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.

Incorporating human mobility data improves forecasts of Dengue fever in Thailand.

Over 390 million people worldwide are infected with dengue fever each year. In the absence of an effective vaccine for general use, national control programs must rely on hospital readiness and targeted vector control to prepare for epidemics, so accurate forecasting remains an important goal. Many dengue forecasting approaches have used environmental data linked to mosquito ecology to predict when epidemics will occur, but these have had mixed results. Conversely, human mobility, an important driver in the spatial spread of infection, is often ignored. Here we compare time-series forecasts of dengue fever in Thailand, integrating epidemiological data with mobility models generated from mobile phone data. We show that geographically-distant provinces strongly connected by human travel have more highly correlated dengue incidence than weakly connected provinces of the same distance, and that incorporating mobility data improves traditional time-series forecasting approaches. Notably, no single model or class of model always outperformed others. We propose an adaptive, mosaic forecasting approach for early warning systems.

Molecular characterization of Plasmodium falciparum antifolate resistance markers in Thailand between 2008 and 2016.

BACKGROUND: Resistance to anti-malarials is a major threat to the control and elimination of malaria. Sulfadoxine-pyrimethamine (SP) anti-malarial treatment was used as a national policy for treatment of uncomplicated falciparum malaria in Thailand from 1973 to 1990. In order to determine whether withdrawal of this antifolate drug has led to restoration of SP sensitivity, the prevalence of genetic markers of SP resistance was assessed in historical Thai samples. METHODS: Plasmodium falciparum DNA was collected from the Thailand-Myanmar, Thailand-Malaysia and Thailand-Cambodia borders during 2008-2016 (N = 233). Semi-nested PCR and nucleotide sequencing were used to assess mutations in Plasmodium falciparum dihydrofolate reductase (pfdhfr), P. falciparum dihydropteroate synthase (pfdhps). Gene amplification of Plasmodium falcipaurm GTP cyclohydrolase-1 (pfgch1) was assessed by quantitative real-time PCR. The association between pfdhfr/pfdhps mutations and pfgch1 copy numbers were evaluated. RESULTS: Mutations in pfdhfr/pfdhsp and pfgch1 copy number fluctuated overtime through the study period. Altogether, 14 unique pfdhfr-pdfhps haplotypes collectively containing quadruple to octuple mutations were identified. High variation in pfdhfr-pfdhps haplotypes and a high proportion of pfgch1 multiple copy number (51% (73/146)) were observed on the Thailand-Myanmar border compared to other parts of Thailand. Overall, the prevalence of septuple mutations was observed for pfdhfr-pfdhps haplotypes. In particular, the prevalence of pfdhfr-pfdhps, septuple mutation was observed in the Thailand-Myanmar (50%, 73/146) and Thailand-Cambodia (65%, 26/40) border. In Thailand-Malaysia border, majority of the pfdhfr-pfdhps haplotypes transaction from quadruple (90%, 9/10) to quintuple (65%, 24/37) during 2008-2016. Within the pfdhfr-pfdhps haplotypes, during 2008-2013 the pfdhps A/S436F mutation was observed only in Thailand-Myanmar border (9%, 10/107), while it was not identified later. In general, significant correlation was observed between the prevalence of pfdhfr I164L (ϕ = 0.213, p-value = 0.001) or pfdhps K540E/N (ϕ = 0.399, p-value ≤ 0.001) mutations and pfgch1 gene amplification. CONCLUSIONS: Despite withdrawal of SP as anti-malarial treatment for 17 years, the border regions of Thailand continue to display high prevalence of antifolate and anti-sulfonamide resistance markers in falciparum malaria. Significant association between pfgch1 amplification and pfdhfr (I164L) or pfdhps (K540E) resistance markers were observed, suggesting a compensatory mutation.

Correction to: How Thailand eliminated lymphatic filariasis as a public health problem.

After publication of this article [1], it was brought to our attention that figure 2 did not display correctly. The correct figure 2 is as below.

How Thailand eliminated lymphatic filariasis as a public health problem.

BACKGROUND: Lymphatic filariasis is endemic in nine of the eleven Member States of the World Health Organization South East Asia Region. This article describes the intensive interventions with the National Programme for Elimination of Lymphatic Filariasis in Thailand since its launch in 2001 till the validation of its elimination in 2017. METHODS: A baseline epidemiological survey was initiated in 2001 to identify both brugian and bancroftian filarial areas and delineate its endemicity. Mass drug administration (MDA) with diethylcarbamazine citrate (DEC) and albendazole (ALB) was implemented in a total of 357 implementation units (IUs) in 11 lymphatic filariasis (LF) endemic provinces. The implementing unit (IU) was a sub-village. Stop-MDA surveys were conducted in 2006 in the 11 LF endemic provinces among population over 6 years of age and children of ≤6 years using immunochromatographic test (ICT) for Wuchereria bancrofti antigen and microfilariae (mf) detection for Brugia malayi. In Narathiwat province, Stop-MDA surveys were done in 2011 using ELISA. Transmission assessment surveys (TAS) were conducted in 2012-2013, 2015 and 2016-2017 among school students in the 6-7-year age-group. Surveillance of migrant populations through the national migrant health checkup were intensified in seven provinces over 2002-2017 for LF antigenaemia using ICT test cards. In four B. malayi endemic provinces, annual surveys to detect LF reservoir in domestic cats commenced in 1994. A 2001 survey of the chronic disease burden for LF established a register of the cumulative number of people with lymphedema/elephantiasis. RESULTS: A total of five rounds of MDA annually were implemented over 2002-2006 in all IUs. Additional annual rounds of MDA were required in 87 IUs of Narathiwat province from 2007 to 2011 due to persistent infection. The annual national drug coverage with MDA over 2002-2012 was in the range of 68.0 to 95.4%. Stop-MDA surveys in 2006 in the 11 LF endemic provinces found nine mf positive cases in seven IUs in Narathiwat province with the highest prevalence of 0.8% (range: 0.1-0.8%). In Narathiwat TAS-1, TAS-2 and TAS-3 detected below transmission threshold rates for B. malayi mf among antibody positive children (0.3, 0.2 and 0.7% respectively). Contact tracing both all mf cases in all three TAS yielded no positive cases. Through the migrant health checkup, a total of 23 477 persons were tested, showing a positive rate of 0.7% (range: 0.1-2.7%) over years 2002-2017. In Narathiwat province, annual ivermectin treatment among cats commenced in 2003 resulting in a decline of mf prevalence among cats from 8.0% in 1995 to 0.8% in 2015. As of April 2017, a total of 99 lymphoedema/elephantiasis patients were registered and followed-up under 34 health facilities. CONCLUSIONS: Thailand over the years 2002 to 2011 conducted extensive MDA with high coverage rates. Through periodic and regular monitoring surveys it delineated LF transmission areas at sub-village level and demonstrated through its evaluation surveys - the Stop-MDA surveys and TAS, below transmission threshold rates that enabled its validation of LF elimination. In September 2017, World Health Organization acknowledged the Ministry of Health Thailand had eliminated lymphatic filariasis as a public health problem.

Emergence and Spread of kelch13 Mutations Associated with Artemisinin Resistance in Plasmodium falciparum Parasites in 12 Thai Provinces from 2007 to 2016.

Artemisinin-based combination therapy (ACT) is the most effective and widely used treatment for uncomplicated Plasmodium falciparum malaria and is a cornerstone for malaria control and prevention globally. Resistance to artemisinin derivatives has been confirmed in the Greater Mekong Subregion (GMS) and manifests as slow parasite clearance in patients and reduced ring stage susceptibility to artemisinins in survival assays. The P. falciparumkelch13 gene mutations associated with artemisinin-resistant parasites are now widespread in the GMS. We genotyped 277 samples collected during an observational study from 2012 to 2016 from eight provinces in Thailand to identify P. falciparum kelch13 mutations. The results were combined with previously reported genotyping results from Thailand to construct a map illustrating the evolution of P. falciparum kelch13 mutations from 2007 to 2016 in that country. Different mutant alleles were found in strains with different geographical origins. The artemisinin resistance-conferring Y493H and R539T mutations were detected mainly in eastern Thailand (bordering Cambodia), while P574L was found only in western Thailand and R561H only in northwestern Thailand. The C580Y mutation was found across the entire country and was nearing fixation along the Thai-Cambodia border. Overall, the prevalence of artemisinin resistance mutations increased over the last 10 years across Thailand, especially along the Thai-Cambodia border. Molecular surveillance and therapeutic efficacy monitoring should be intensified in the region to further assess the extent and spread of artemisinin resistance.

The sources of treatment of sexually transmissible infections in a rural community in central Thailand.

BACKGROUND: Sexually transmissible infection (STI) rates in Thailand declined from 1986 to 1994, but levelled off until 2002. This study documents the distribution of STI cases attending major treatment venues and the quality of treatment in a rural area. METHODS: A cross sectional study was conducted in January and June 2001 in all 42 health-care facilities in the study district, including the hospital STI and outpatient clinics, private clinics, local health centres and pharmacies. Quality of care was assessed by documenting appropriate syndromic treatment according to the World Health Organization Syndromic Case Management Guidelines. RESULTS: Over half of STI patients (60%) sought treatment from pharmacies (35%) and health centres (25%), the facilities least capable of accurately diagnosing and treating STI. Only 0-59% were adequately treated. CONCLUSIONS: The quality of services needs to be improved and innovative strategies developed and implemented to address the problems of acceptability, stigmatisation, access and quality of STI services in Thailand.