Ivermectin Accelerates Circulating Nonstructural Protein 1 (NS1) Clearance in Adult Dengue Patients: A Combined Phase 2/3 Randomized Double-blinded Placebo Controlled Trial.

BACKGROUND: Dengue is the most significant mosquito-borne viral disease; there are no specific therapeutics. The antiparasitic drug ivermectin efficiently inhibits the replication of all 4 dengue virus serotypes in vitro. METHODS: We conducted 2 consecutive randomized, double-blind, placebo-controlled trials in adult dengue patients to evaluate safety and virological and clinical efficacies of ivermectin. After a phase 2 trial with 2 or 3 days of 1 daily dose of 400 µg/kg ivermectin, we continued with a phase 3, placebo-controlled trial with 3 days of 400 µg/kg ivermectin. RESULTS: The phase 2 trial showed a trend in reduction of plasma nonstructural protein 1 (NS1) clearance time in the 3-day ivermectin group compared with placebo. Combining phase 2 and 3 trials, 203 patients were included in the intention to treat analysis (100 and 103 patients receiving ivermectin and placebo, respectively). Dengue hemorrhagic fever occurred in 24 (24.0%) of ivermectin-treated patients and 32 (31.1%) patients receiving placebo (P = .260). The median (95% confidence interval [CI]) clearance time of NS1 antigenemia was shorter in the ivermectin group (71.5 [95% CI 59.9-84.0] hours vs 95.8 [95% CI 83.9-120.0] hours, P = .014). At discharge, 72.0% and 47.6% of patients in the ivermectin and placebo groups, respectively had undetectable plasma NS1 (P = .001). There were no differences in the viremia clearance time and incidence of adverse events between the 2 groups. CONCLUSIONS: A 3-day 1 daily dose of 400 µg/kg oral ivermectin was safe and accelerated NS1 antigenemia clearance in dengue patients. However, clinical efficacy of ivermectin was not observed at this dosage regimen.

Immunome and immune complex-forming components of Brugia malayi identified by microfilaremic human sera.

Adult Brugia malayi proteins with high potential as epidemiological markers, diagnostic and therapeutic targets, and/or vaccine candidates were revealed by using microfilaremic human sera and an immunoproteomic approach. They were HSP70, cytoplasmic intermediate filament protein, independent phosphoglycerate mutase, and enolase. Brugia malayi microfilaria-specific proteins that formed circulating immune complexes (ICs) were investigated. The IC-forming proteins were orthologues of hypothetical protein Bm1_12480, Pao retrotransposon peptidase family protein, uncoordinated protein 44, NAD-binding domain containing protein of the UDP-glucose/GDP-mannose dehydrogenase family which contained ankyrin repeat region, ZU5 domain with C-terminal death domain, C2 domain containing protein, and FLJ90013 protein of the eukaryotic membrane protein family. Antibodies to these proteins were not free in the microfilaremic sera, raising the possible role of the IC-forming proteins in an immune evasion mechanism of the circulating microfilariae to avoid antibody-mediated-host immunity. Moreover, detection of these ICs should be able to replace the inconvenient night blood sampling for microfilaria in an evaluation of efficacy of anti-microfilarial agents.

First study of topical selamectin efficacy for treating cats naturally infected with Brugia malayi and Brugia pahangi under field conditions.

Lymphatic filariae are important human and animal parasites. Infection by these parasites could lead to severe morbidity and has significant socioeconomic impacts. Topical selamectin is a semi-synthetic macrocyclic lactone that is widely used to prevent heartworm infection. Up until now, there were no studies that investigated the efficacy of selamectin in lymphatic filariae. Therefore, we aimed to study the chemotherapeutic and chemoprophylactic efficacies of selamectin use for cats in brugian filariasis-endemic areas in Southern Thailand. To assess chemotherapeutic efficacy of topical selamectin, eight Brugia malayi and six Brugia pahangi microfilaremic cats were treated with a single administration of topical selamectin. For chemoprophylactic efficacy assessment, a single application of topical selamectin was administrated to 9 healthy, uninfected cats. The cats in both groups were subjected to a monthly blood testing for microfilariae and filarial DNA for 1 year. Topical selamectin treatment in B. malayi and B. pahangi microfilaremic cats showed 100% effectivity in eradicating microfilaremia but only 78.5% effectivity in eliminating filarial DNA. In the chemoprophylactic group, selamectin demonstrated 66.7% efficacy in preventing B. malayi infection. Our findings suggest that a single administration of 6 mg/kg topical selamectin given every two months could effectively prevent B. malayi infection. Application of topical selamectin twice a year could block circulating microfilariae. Since there are no treatment guidelines currently available for lymphatic filarial infection in cats, the data obtained from this study could be used to guide the management of brugian lymphatic filarial infection in reservoir cats.

Distribution of pfmdr1 polymorphisms in Plasmodium falciparum isolated from Southern Thailand.

BACKGROUND: Drug resistance in Plasmodium falciparum is a major problem in malaria control especially along the Thai-Myanmar and Thai-Cambodia borders. To date, a few molecular markers have been identified for anti-malarial resistance in P. falciparum, including the P. falciparum chloroquine resistance transporter (pfcrt) and the P. falciparum multidrug resistance 1 (pfmdr1). However no information is available regarding the distribution pattern of these gene polymorphisms in the parasites from the Thai-Malaysia border. This study was conducted to compare the distribution pattern of the pfcrt and pfmdr1 polymorphisms in the parasites from the lower southern provinces, Thai-Malaysia border and the upper southern provinces, Thai-Myanmar border. In addition, in vitro sensitivities of anti-malarial drugs including chloroquine, mefloquine, quinine, and artesunate were determined. METHODS: In all, 492 P. falciparum-positive blood samples were collected from the lower southern provinces: Songkhla, Yala and Narathiwas. From the upper southern part of Thailand, Ranong and Chumphon, 66 samples were also collected. Polymorphisms of the pfcrt and the pfmdr1 gene were determined using PCR techniques. In vitro sensitivities of anti-malarial drugs were determined using radioisotopic method. RESULTS: All parasites from both areas contained the pfcrt 76 T allele. The pfmdr1 86Y allele was significantly more common in the parasites isolated from the lower southern areas. In contrast, the pfmdr1 184F allele was predominant among the parasites from the upper southern areas especially Ranong. In addition, the parasites from Ranong contained higher copy numbers than the parasites from other provinces. All adapted parasite isolates exhibited CQ-resistant phenotype. Neither QN nor MQ resistance was detected in these isolates. CONCLUSION: The parasites from Thai-Malaysia border exhibited different resistant patterns compared to other areas along the international border of Thailand. This information will be useful for anti-malarial drug policy in Thailand.

Animal reservoirs and potential vectors of Leishmania siamensis in southern Thailand.

Leishmania siamensis is newly described as the causative pathogen of autochthonous leishmaniasis in Thailand. Potential vectors and animal reservoirs of L. siamensis are not thoroughly studied. An environmental survey was carried out in the affected area in two provinces in southern Thailand: Songkhla and Nakhon Si Thammarat. Ninety-nine villagers, 378 sandflies, and potential animal reservoirs were examined. Leishmania DNA amplicon was identified in two species of female sandflies, Sergentomyia (Neophlebotomus) and Sergentomyia (Parrotomyia) barraudi. The DNA amplicon was also identified in black rats (Rattus rattus). A phylogenetic tree of confirmed patients, sandflies and black rats fell into a single clade and separate from other Leishmania species. This study showed the potential involvement of R. rattus and Sergentomyia (Neophlebotomus and Parrotomyia) sandflies in transmission of L. siamensis.

Effectiveness, Safety, and Acceptability of Primaquine Mass Drug Administration in Low-Endemicity Areas in Southern Thailand: Proof-of-Concept Study.

BACKGROUND: A challenge in achieving the malaria-elimination target in the Greater Mekong Subregion, including Thailand, is the predominance of Plasmodium vivax malaria, which has shown extreme resilience to control measures. OBJECTIVE: This proof-of-concept study aimed to provide evidence for implementing primaquine mass drug administration (pMDA) as a strategy for P. vivax elimination in low-endemicity settings. METHODS: The study employed a mixed-methods trial to thoroughly evaluate the effectiveness, safety, acceptability, and community engagement of pMDA. The quantitative part was designed as a 2-period cluster-crossover randomized controlled trial. The intervention was pMDA augmented to the national prevention and control standards with directly observed treatment (DOT) by village health volunteers. The qualitative part employed in-depth interviews and brainstorming discussions. The study involved 7 clusters in 2 districts of 2 southern provinces in Thailand with persistently low P. vivax transmission. In the quantitative part, 5 cross-sectional blood surveys were conducted in both the pMDA and control groups before and 3 months after pMDA. The effectiveness of pMDA was determined by comparing the proportions of P. vivax infections per 1000 population between the 2 groups, with a multilevel zero-inflated negative binomial model adjusted for cluster and time as covariates and the interaction. The safety data comprised adverse events after drug administration. Thematic content analysis was used to assess the acceptability and engagement of stakeholders. RESULTS: In the pre-pMDA period, the proportions of P. vivax infections in the pMDA (n=1536) and control (n=1577) groups were 13.0 (95% CI 8.2-20.4) and 12.0 (95% CI 7.5-19.1), respectively. At month 3 post-pMDA, these proportions in the pMDA (n=1430) and control (n=1420) groups were 8.4 (95% CI 4.6-15.1) and 5.6 (95% CI 2.6-11.5), respectively. No statistically significant differences were found between the groups. The number of malaria cases reduced in all clusters in both groups, and thus, the impact of pMDA was inconclusive. There were no major safety concerns. Acceptance among the study participants and public health care providers at local and national levels was high, and they believed that pMDA had boosted awareness in the community. CONCLUSIONS: pMDA was associated with high adherence, safety, and tolerability, but it may not significantly impact P. vivax transmission. As this was a proof-of-concept study, we decided not to scale up the intervention with larger clusters and samples. An alternative approach involving a targeted primaquine treatment strategy with primaquine and DOT is currently being implemented. We experienced success regarding effective health care workforces at point-of-care centers, effective collaborations in the community, and commitment from authorities at local and national levels. Our efforts boosted the acceptability of the malaria-elimination initiative. Community engagement is recommended to achieve elimination targets. TRIAL REGISTRATION: Thai Clinical Trials Registry TCTR20190806004; https://www.thaiclinicaltrials.org/show/TCTR20190806004.

Feasibility of ultra-low-volume indoor space spraying for dengue control in Southern Thailand.

OBJECTIVES: To assess the feasibility of conducting standard indoor space spraying using ultra-low-volume (SID-ULV) in terms of willingness to pay (WTP) and ability to pay (ATP) and ability to conduct space spraying by local administrative organisations (LAO) in lower Southern Thailand. METHODS: Cross-sectional study. The executive leaders of each LAO were asked to state their WTP and ATP for SID-ULV. Willingness to pay was measured by the payment card and open-ended question methods. Ability to pay was calculated using the budget allocation for space spraying and estimated expenditure for SID-ULV. Ability to conduct the SID-ULV was assessed by interviewing the spraymen. Average WTP and ATP were calculated and uncertainties were estimated using a bootstrapping technique. RESULTS: Ninty-three percent of executive leaders were willing to pay for SID-ULV. The average WTP per case was USD 259 (95% confidence interval [CI] 217-303). Thirty-eight percent of all LAO had actual ATP and 60% had ideal ATP. The average annual budget allocated for space spraying was USD 2327 (95% CI: 1654-3138). The amount of money LAO were willing to pay did not vary significantly between their different types, but ATP did. Thirty-two percent of spraymen could not complete all nine procedures of SID-ULV. CONCLUSIONS: Although WTP for SID-ULV space spraying was high, ATP was low, which revealed the flexibility of budget allocation for SID-ULV in each LAO. The spraymen require training in SID-ULV space spraying.

Underrecognized mildly symptomatic viremic dengue virus infections in rural Thai schools and villages.

BACKGROUND: The understanding of dengue virus (DENV) transmission dynamics and the clinical spectrum of infection are critical to informing surveillance and control measures. Geographic cluster studies can elucidate these features in greater detail than cohort studies alone. METHODS: A 4-year longitudinal cohort and geographic cluster study was undertaken in rural Thailand. Cohort children underwent pre-/postseason serology and active school absence-based surveillance to detect inapparent and symptomatic dengue. Cluster investigations were triggered by cohort dengue and non-dengue febrile illnesses (positive and negative clusters, respectively). RESULTS: The annual cohort incidence of symptomatic dengue ranged from 1.3% to 4.4%. DENV-4 predominated in the first 2 years, DENV-1 in the second 2 years. The inapparent-to-symptomatic infection ratio ranged from 1.1:1 to 2.9:1. Positive clusters had a 16.0% infection rate, negative clusters 1.1%. Of 119 infections in positive clusters, 59.7% were febrile, 20.2% were afebrile with other symptoms, and 20.2% were asymptomatic. Of 16 febrile children detected during cluster investigations who continued to attend school, 9 had detectable viremia. CONCLUSIONS: Dengue transmission risk was high near viremic children in both high- and low-incidence years. Inapparent infections in the cohort overestimated the rate of asymptomatic infections. Ambulatory children with mild febrile viremic infections could represent an important component of dengue transmission.

Cost of standard indoor ultra-low-volume space spraying as a method to control adult dengue vectors.

OBJECTIVES: To access the costs of standard indoor ultra-low-volume (SID-ULV) space spraying for controlling dengue vectors in Thailand. METHODS: Resources related to SID-ULV space spraying as a method to control dengue vectors between July and December 2009 were identified, measured and valued taking a societal perspective into consideration. Information on costs was collected from direct observations, interviews and bookkeeping records. Uncertainty of unit costs was investigated using a bootstrap technique. RESULTS: Costs of SID-ULV were calculated from 18 new dengue cases that covered 1492 surrounding houses. The average coverage of the SID-ULV was 64.4%. In the first round of spraying, 53% of target houses were sprayed and 44.6% in the second round, of which 69.2% and 54.7% received entire indoor space spraying. Unit costs per case, per 10 houses and per 100 m(2) were USD 705 (95% Confidence Interval CI, 539-888), 180 (95% CI, 150-212) and USD 23 (95% CI, 17-30). The majority of SID-ULV unit cost per case was attributed to productivity loss (83.9%) and recurrent costs (15.2%). The unit cost of the SID-ULV per case and per house in rural was 2.8 and 1.6 times lower than municipal area. The estimated annual cost of SID-ULV space spraying from 2005 to 2009 using healthcare perspective ranged from USD 5.3 to 10.3 million. CONCLUSIONS: The majority of the cost of SID-ULV space spraying was attributed to productivity loss. Potential productivity loss influences the achievement of high coverage, so well-planned SID-ULV space spraying strategies are needed to reduce costs.

Identification of dengue virus in Aedes mosquitoes and patients' sera from Si Sa Ket Province, Thailand.

Dengue fever (DF), dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) are the re-emerging infectious diseases caused by dengue (DEN) virus, transmitted by Aedes mosquito. There are more than 100,000 cases of dengue infection and more than 100 deaths annually in Thailand. Virological surveillance for DEN viruses is used as an early warning system to predict outbreaks. The seroprevalence of infection and serotypes of DEN virus in 116 pediatric patients at Si Sa Ket Province, Thailand were analyzed during June to September 2004. At the same period, Aedes mosquitoes were caught from patients' and their neighbors' houses, from control houses, located in villages with no report of dengue infection during the previous 3 years. The majority of DHF cases were secondary infections of DEN-2 and DEN-4 serotypes. Of the 1,652 Aedes mosquitoes collected 1,583 were Ae. aegypti and 69 Ae. albopictus. Ten mosquitoes from each house were pooled and dengue viruses were determined using RT-PCR assay; only 1 positive pooled was found. Although the dengue infection rate in the field caught mosquitoes was low, the existing dengue virus control program in transmission areas by aerial spraying to destroy the larva breeding sites should be continued.

The serotype-independent but concentration-dependent enhancing antibodies among Thai dengue patients.

Antibody-dependent enhancement of infection (ADE) is central to explaining the development of severe disease at the end of post-dengue virus infection. Non-neutralizing anti-dengue antibodies bound to the dengue virion enhances the virus entrance into the target cells via the Fc receptor. The titer of enhancing antibodies in dengue patients is not determined during dengue virus infection. Sensitive flow cytometry detecting dengue virus-infected K562 cells was used to quantitate enhancing activity among Thai DF and DHF patients against four serotypes and the patient's dengue isolate. The titer was defined as the reciprocal of the final dilution that loses enhancing activity. The serum of Thai patients confirmed to have dengue infection were found to have high titers of enhancing antibodies and increased gradually through the convalescent phase of infection. The enhancing antibody titers were not different among the four serotypes or from the infecting isolate. The anti-dengue antibodies from dengue patients can enhance dengue virus infections in a concentration-dependent, serotype-independent manner.

Malaria Research for Tailored Control and Elimination Strategies in the Greater Mekong Subregion.

The malaria landscape in the Greater Mekong Subregion has experienced drastic changes with the ramp-up of the control efforts, revealing formidable challenges that slowed down the progress toward malaria elimination. Problems such as border malaria and cross-border malaria introduction, multidrug resistance in Plasmodium falciparum, the persistence of Plasmodium vivax, the asymptomatic parasite reservoirs, and insecticide resistance in primary vectors require integrated strategies tailored for individual nations in the region. In recognition of these challenges and the need for research, the Southeast Asian International Center of Excellence for Malaria Research has established a network of researchers and stakeholders and conducted basic and translational research to identify existing and emerging problems and develop new countermeasures. The installation of a comprehensive disease and vector surveillance system at sentinel sites in border areas with the implementation of passive/active case detection and cross-sectional surveys allowed timely detection and management of malaria cases, provided updated knowledge for effective vector control measures, and facilitated the efficacy studies of antimalarials. Incorporating sensitive molecular diagnosis to expose the significance of asymptomatic parasite reservoirs for sustaining transmission helped establish the necessary evidence to guide targeted control to eliminate residual transmission. In addition, this program has developed point-of-care diagnostics to monitor the quality of artemisinin combination therapies, delivering the needed information to the drug regulatory authorities to take measures against falsified and substandard antimalarials. To accelerate malaria elimination, this program has actively engaged with stakeholders of all levels, fostered vertical and horizontal collaborations, and enabled the effective dissemination of research findings.

The Potential Container Habitats of Chikungunya Vector in Outbreak Area of Southern Thailand.

Chikungunya virus (CHIKV) is primarily transmitted by Aedes mosquitoes and is responsible for reemerging disease internationally. Container habitats of immature Aedes mosquitoes are often found around residential areas, thus water-holding container investigation is an important vector control strategy. This study aimed to survey mosquito species in container inhabiting stages and water-holding containers associated with the CHIKV outbreak in urban areas within the 4 villages of Hat Yai district in Songkhla province during 2019. The results indicated that of the 75 houses surveyed, 34 had water-holding containers; 78 out of 438 containers were positive for mosquitoes; and 34 were positive for mosquito stages. The house index (HI), Breteau index (BI), container index (CI), and pupal index (PI) were 46.87, 93.75, 14.92, and 271.88 for case houses, respectively. Specific container index (SCI) showed discarded containers such as bottles, cans, and tires. The findings suggest that Aedes aegypti was predominant in the surveyed urban area and might be the vector responsible for CHIKV transmission in Songkhla province.

Chikungunya Fever in Southern Thailand, 2018.

Infection by the mosquito-borne chikungunya virus (CHIKV) causes acute febrile illness and debilitating arthralgia. Outbreaks are sometimes not recognized because of its clinical resemblance to the more common dengue fever ubiquitous in tropical countries. An upsurge of dengue-like illness was reported in Satun province located in southern Thailand during the rainy season in 2018. We investigated probable outbreak of CHIKV disease. We collected serum samples from 127 patients and tested for CHIKV infection based on nucleic acid and serological tests. CHIKV RNA amplified by real-time reverse-transcription polymerase chain reaction (RT-PCR) and IgM antibody against CHIKV were determined by immunochromatographic rapid test. Mosquitoes in the community were also trapped and tested for CHIKV. Conventional RT-PCR on initially positive samples was performed to obtain nucleotide sequences for subsequent phylogenetic analysis. In all, 39% (50/127) of the samples tested positive for CHIKV RNA, IgM, or both. Of these, CHIKV RNA was identified in 17% (21/127) of the samples. Fourteen percent (18/127) of the samples were simultaneously positive for both IgM and IgG, which suggest recent infection. One sample tested positive for both CHIKV IgM and RNA. Several samples from Aedes aegypti and Aedes albopictus mosquitoes were also CHIKV RNA-positive. Sequence analysis revealed that the Satun CHIKV belonged to the Indian Ocean lineage within the East/Central/South African (ECSA) clade with residues K211E and A226 in the E1 gene, and G205S and V264A in the E2 gene. The ECSA strain of CHIKV continues to evolve and possesses virulent potential despite causing prior outbreaks in the region.

Distribution of Phlebotomine Sandflies in the Cave Area of Satun Province, Thailand.

Leishmaniasis, a sandfly-transmitted protozoan infection, is a neglected health threat in Thailand and the information on its vector is scarce. This study aimed to identify sandfly distribution, abundance, and environmental conditions of natural breeding sites in the cave areas of Satun Province, where previous cases of leishmaniasis were reported. Sandflies were collected during a six-month period using CDC light traps and modified emergence traps. Species distribution, relative abundance, and environmental conditions of potential breeding sites were determined. Our survey of 12,790 sandflies found the highest female abundance in April-May. We identified six known species, the most prevalent being Sergentomyia anodontis. We also found S. barraudi, a potential Leishmania spp. vector, distributing in this area. Most male sandflies had partially rotated genitalia, indicating the breeding site proximity to our trap locations. Potential resting/breeding sites were discovered outside the cave during February-March, and inside during May-June. The environmental parameters showed warm climate, moderate humidity, moderately alkaline pH, moderate-to-high macronutrients, and low-to-high organic matters. In summary, our study provided the spatiotemporal distribution and environmental condition of sandfly potential breeding sites in the cave areas of Satun Province. This data may contribute to more effective vector surveillance programs in the future.

Pharmacokinetics of ivermectin in cats receiving a single subcutaneous dose.

Ivermectin is effective against ecto- and endoparasites. It is included in a plan of the Filariasis Division, Thailand for filariasis control and prevention by interrupting transmission of Brugia malayi-microfilariae from cat reservoirs to humans via mosquitoes. The pharmacokinetics of ivermectin in eight healthy cats receiving a single subcutaneous dose of 0.2mg/kg was investigated. Jugular blood samples were collected periodically for up to 30days after dosing. The serum ivermectin concentrations were measured by high performance liquid chromatography with fluorescence detection. The pharmacokinetic parameters (mean+/-S.D.) derived from one-compartment model analysis were as follows: T(max) 1.22+/-0.49day, C(max) 16.75+/-4.04ng/mL, k(ab) 2.62+/-1.86day(-1), t(1/2)(ab) 0.27+/-0.25day, k(el) 0.27+/-0.14day(-1), t(1/2)(el) 2.53+/-2.24day, V(d)/F 9.81+/-5.41L/kg, Cl/F 2.21+/-0.69L/kg/day and AUC(0-->infinity) 98.31+/-30.52ngday/mL. In conclusion, the pharmacokinetics of ivermectin in cats receiving a single dose of 0.2mg/kg by subcutaneous injection revealed a rapid absorption, high distribution, slow elimination and high possibility for the elimination of B. malayi-microfilariae from currently endemic regions.

Outbreak of chikungunya fever in Thailand and virus detection in field population of vector mosquitoes, Aedes aegypti (L.) and Aedes albopictus Skuse (Diptera: Culicidae).

We investigated chikungunya fever outbreak in the southern part of Thailand. Human plasma specimens obtained from suspected patients and adult wild-caught mosquitoes were detected for chikungunya virus employing reverse transcriptase-polymerase chain reaction technique. Chikungunya virus was detected in about half of the blood specimens whereas a range of 5.5 to 100% relative infection rate was found in both sexes of the vector mosquitoes, Aedes aegypti (L.) and Ae. albopictus Skuse. The infection rate in Ae. albopictus was higher than in Ae. aegypti, with relative infection rate in male of both species being higher than in female. The appearance of chikungunya virus in adult male mosquitoes of both species reveals a role of transovarial transmission of the virus in field population of the mosquito vectors. These findings have provided further understanding of the relationship among mosquito vectors, chikungunya virus and epidemiology of chikungunya fever in Thailand.

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.