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Abstract Background Malaria in Southeast Asia frequently clusters along international borders. For example, while most of Thailand is malaria free, the border region shared with Myanmar continues to have endemic malaria. This spatial pattern is the result of complex interactions between landscape, humans, mosquito vectors, and malaria parasites. An understanding of these complex ecological and socio-cultural interactions is important for designing and implementing malaria elimination efforts in the region. This article offers an ecological perspective on the malaria situation along the Thailand–Myanmar border. Discussion This border region is long (2000 km), mountainous, and the environment ranges from thick forests to growing urban settlements and wet-rice fields. It is also a biologically diverse region. All five species of malaria known to naturally infect humans are present. At least three mosquito vector species complexes, with widely varying behavioural characteristics, exist in the area. The region is also a hub for ethnic diversity, being home to over ten different ethnolinguistic groups, several of which have been engaged in conflict with the Myanmar government now for over half a century. Given the biological and ethnic diversity, as well as the complex socio-political context, malaria control and elimination in the region is challenging. Conclusion Despite these complexities, multipronged approaches including collaborations with multiple local organizations, quick access to diagnosis and treatment, prevention of mosquito bites, radical cure of parasites, and mass drug administration appear to be drastically decreasing Plasmodium falciparum infections. Such approaches remain crucial as the region moves toward elimination of P. falciparum and potentially Plasmodium vivax .

BackgroundMalaria in Southeast Asia frequently clusters along international borders. For example, while most of Thailand is malaria free, the border region shared with Myanmar continues to have endemic malaria. This spatial pattern is the result of complex interactions between landscape, humans, mosquito vectors, and malaria parasites. An understanding of these complex ecological and socio-cultural interactions is important for designing and implementing malaria elimination efforts in the region. This article offers an ecological perspective on the malaria situation along the Thailand-Myanmar border.DiscussionThis border region is long (2000 km), mountainous, and the environment ranges from thick forests to growing urban settlements and wet-rice fields. It is also a biologically diverse region. All five species of malaria known to naturally infect humans are present. At least three mosquito vector species complexes, with widely varying behavioural characteristics, exist in the area. The region is also a hub for ethnic diversity, being home to over ten different ethnolinguistic groups, several of which have been engaged in conflict with the Myanmar government now for over half a century. Given the biological and ethnic diversity, as well as the complex socio-political context, malaria control and elimination in the region is challenging.ConclusionDespite these complexities, multipronged approaches including collaborations with multiple local organizations, quick access to diagnosis and treatment, prevention of mosquito bites, radical cure of parasites, and mass drug administration appear to be drastically decreasing Plasmodium falciparum infections. Such approaches remain crucial as the region moves toward elimination of P. falciparum and potentially Plasmodium vivax.

Background: Attitudes and understanding of clinical trial participants regarding biobanking are not fully understood. This study explored the baseline understanding of biobanking amongst clinical trial participants in Thailand, to determine factors and attitudes which may affect an individuals' decision to consent to involvement in biobanking studies.Methods: Using qualitative research methodology, clinical trial participants (n=24) who were already enrolled in clinical research studies at the Hospital for Tropical Diseases were given an information sheet explaining biobanking. An in-depth interview was then conducted along with a demographic questionnaire. The results were analyzed using NVIVO 10 software.Results: Fifty four percent felt they had a clearer understanding of biobanking after reading the brochure. All the respondents were willing to donate a blood sample to a biobank, and 22/24 wer–e positive towards the concept of biobanking, citing an altruistic desire to help future medical research efforts, potential benefits for their family and prospect of learning more about their own health from future studies such as genetic projects. There was an inverse relationship between the level of education / income of participants and their desire to receive direct financial compensation for donating a sample. Sixty two percent agreed that their sample could be stored and used indefinitely even after their death. Interviewees wishing to have clear structures of consent, protection of confidentiality of personal information, and fifty four percent wished to be contacted to specifically consent for future studies using their sample. They felt governance structures should involve researchers, a specific biobank committee and Government organizations. Whilst most responses were positive, including the potential for Thai samples to be used by researchers in other countries, the level of agreement was markedly lower if samples might be used by commercial companies such as pharmaceutical industry (73% neutral or disagreed).Conclusions: Most respondents have a clearer understanding and positive attitude towards the concept of biobanking. This study suggests that researchers should provide both written and oral information during enrollment for biobanking studies, giving time for participants to better understand the purpose of biobanking studies prior to signing a consent form. They have implications for the planning and establishment of biobanking facilities in Thailand.

National Malaria Control Programmes (NMCPs) currently make limited use of parasite genetic data. We have developed GenRe-Mekong, a platform for genetic surveillance of malaria in the Greater Mekong Subregion (GMS) that enables NMCPs to implement large-scale surveillance projects by integrating simple sample collection procedures in routine public health procedures. Samples from symptomatic patients are processed by SpotMalaria, a high-throughput system that produces a comprehensive set of genotypes comprising several drug resistance markers, species markers and a genomic barcode. GenRe-Mekong delivers Genetic Report Cards, a compendium of genotypes and phenotype predictions used to map prevalence of resistance to multiple drugs. GenRe-Mekong has worked with NMCPs and research projects in eight countries, processing 9623 samples from clinical cases. Monitoring resistance markers has been valuable for tracking the rapid spread of parasites resistant to the dihydroartemisinin-piperaquine combination therapy. In Vietnam and Laos, GenRe-Mekong data have provided novel knowledge about the spread of these resistant strains into previously unaffected provinces, informing decision-making by NMCPs. GenRe-Mekong provides detailed knowledge about drug resistance at a local level, and facilitates data sharing at a regional level, enabling cross-border resistance monitoring and providing the public health community with valuable insights. The project provides a rich open data resource to benefit the entire malaria community. The GenRe-Mekong project is funded by the Bill and Melinda Gates Foundation (OPP11188166, OPP1204268). Genotyping and sequencing were funded by the Wellcome Trust (098051, 206194, 203141, 090770, 204911, 106698/B/14/Z) and Medical Research Council (G0600718). A proportion of samples were collected with the support of the UK Department for International Development (201900, M006212), and Intramural Research Program of the National Institute of Allergy and Infectious Diseases.

International audience ; BACKGROUND:The emergence and spread of multidrug-resistant Plasmodium falciparum in the Greater Mekong Subregion (GMS) threatens global malaria elimination efforts. Mass drug administration (MDA), the presumptive antimalarial treatment of an entire population to clear the subclinical parasite reservoir, is a strategy to accelerate malaria elimination. We report a cluster randomised trial to assess the effectiveness of dihydroartemisinin-piperaquine (DP) MDA in reducing falciparum malaria incidence and prevalence in 16 remote village populations in Myanmar, Vietnam, Cambodia, and the Lao People's Democratic Republic, where artemisinin resistance is prevalent.METHODS AND FINDINGS:After establishing vector control and community-based case management and following intensive community engagement, we used restricted randomisation within village pairs to select 8 villages to receive early DP MDA and 8 villages as controls for 12 months, after which the control villages received deferred DP MDA. The MDA comprised 3 monthly rounds of 3 daily doses of DP and, except in Cambodia, a single low dose of primaquine. We conducted exhaustive cross-sectional surveys of the entire population of each village at quarterly intervals using ultrasensitive quantitative PCR to detect Plasmodium infections. The study was conducted between May 2013 and July 2017. The investigators randomised 16 villages that had a total of 8,445 residents at the start of the study. Of these 8,445 residents, 4,135 (49%) residents living in 8 villages, plus an additional 288 newcomers to the villages, were randomised to receive early MDA; 3,790 out of the 4,423 (86%) participated in at least 1 MDA round, and 2,520 out of the 4,423 (57%) participated in all 3 rounds. The primary outcome, P. falciparum prevalence by month 3 (M3), fell by 92% (from 5.1% [171/3,340] to 0.4% [12/2,828]) in early MDA villages and by 29% (from 7.2% [246/3,405] to 5.1% [155/3,057]) in control villages. Over the following 9 months, the P. falciparum prevalence increased to 3.3% (96/2,881) in early MDA villages and to 6.1% (128/2,101) in control villages (adjusted incidence rate ratio 0.41 [95% CI 0.20 to 0.84]; p = 0.015). Individual protection was proportional to the number of completed MDA rounds. Of 221 participants with subclinical P. falciparum infections who participated in MDA and could be followed up, 207 (94%) cleared their infections, including 9 of 10 with artemisinin- and piperaquine-resistant infections. The DP MDAs were well tolerated; 6 severe adverse events were detected during the follow-up period, but none was attributable to the intervention.CONCLUSIONS:Added to community-based basic malaria control measures, 3 monthly rounds of DP MDA reduced the incidence and prevalence of falciparum malaria over a 1-year period in areas affected by artemisinin resistance. P. falciparum infections returned during the follow-up period as the remaining infections spread and malaria was reintroduced from surrounding areas. Limitations of this study include a relatively small sample of villages, heterogeneity between villages, and mobility of villagers that may have limited the impact of the intervention. These results suggest that, if used as part of a comprehensive, well-organised, and well-resourced elimination programme, DP MDA can be a useful additional tool to accelerate malaria elimination.

BACKGROUND:The emergence and spread of multidrug-resistant Plasmodium falciparum in the Greater Mekong Subregion (GMS) threatens global malaria elimination efforts. Mass drug administration (MDA), the presumptive antimalarial treatment of an entire population to clear the subclinical parasite reservoir, is a strategy to accelerate malaria elimination. We report a cluster randomised trial to assess the effectiveness of dihydroartemisinin-piperaquine (DP) MDA in reducing falciparum malaria incidence and prevalence in 16 remote village populations in Myanmar, Vietnam, Cambodia, and the Lao People's Democratic Republic, where artemisinin resistance is prevalent. METHODS AND FINDINGS:After establishing vector control and community-based case management and following intensive community engagement, we used restricted randomisation within village pairs to select 8 villages to receive early DP MDA and 8 villages as controls for 12 months, after which the control villages received deferred DP MDA. The MDA comprised 3 monthly rounds of 3 daily doses of DP and, except in Cambodia, a single low dose of primaquine. We conducted exhaustive cross-sectional surveys of the entire population of each village at quarterly intervals using ultrasensitive quantitative PCR to detect Plasmodium infections. The study was conducted between May 2013 and July 2017. The investigators randomised 16 villages that had a total of 8,445 residents at the start of the study. Of these 8,445 residents, 4,135 (49%) residents living in 8 villages, plus an additional 288 newcomers to the villages, were randomised to receive early MDA; 3,790 out of the 4,423 (86%) participated in at least 1 MDA round, and 2,520 out of the 4,423 (57%) participated in all 3 rounds. The primary outcome, P. falciparum prevalence by month 3 (M3), fell by 92% (from 5.1% [171/3,340] to 0.4% [12/2,828]) in early MDA villages and by 29% (from 7.2% [246/3,405] to 5.1% [155/3,057]) in control villages. Over the following 9 months, the P. falciparum prevalence increased to 3.3% (96/2,881) in early MDA villages and to 6.1% (128/2,101) in control villages (adjusted incidence rate ratio 0.41 [95% CI 0.20 to 0.84]; p = 0.015). Individual protection was proportional to the number of completed MDA rounds. Of 221 participants with subclinical P. falciparum infections who participated in MDA and could be followed up, 207 (94%) cleared their infections, including 9 of 10 with artemisinin- and piperaquine-resistant infections. The DP MDAs were well tolerated; 6 severe adverse events were detected during the follow-up period, but none was attributable to the intervention. CONCLUSIONS:Added to community-based basic malaria control measures, 3 monthly rounds of DP MDA reduced the incidence and prevalence of falciparum malaria over a 1-year period in areas affected by artemisinin resistance. P. falciparum infections returned during the follow-up period as the remaining infections spread and malaria was reintroduced from surrounding areas. Limitations of this study include a relatively small sample of villages, heterogeneity between villages, and mobility of villagers that may have limited the impact of the intervention. These results suggest that, if used as part of a comprehensive, well-organised, and well-resourced elimination programme, DP MDA can be a useful additional tool to accelerate malaria elimination. TRIAL REGISTRATION:ClinicalTrials.gov NCT01872702.

BackgroundThe emergence and spread of multidrug-resistant Plasmodium falciparum in the Greater Mekong Subregion (GMS) threatens global malaria elimination efforts. Mass drug administration (MDA), the presumptive antimalarial treatment of an entire population to clear the subclinical parasite reservoir, is a strategy to accelerate malaria elimination. We report a cluster randomised trial to assess the effectiveness of dihydroartemisinin-piperaquine (DP) MDA in reducing falciparum malaria incidence and prevalence in 16 remote village populations in Myanmar, Vietnam, Cambodia, and the Lao People's Democratic Republic, where artemisinin resistance is prevalent.Methods and findingsAfter establishing vector control and community-based case management and following intensive community engagement, we used restricted randomisation within village pairs to select 8 villages to receive early DP MDA and 8 villages as controls for 12 months, after which the control villages received deferred DP MDA. The MDA comprised 3 monthly rounds of 3 daily doses of DP and, except in Cambodia, a single low dose of primaquine. We conducted exhaustive cross-sectional surveys of the entire population of each village at quarterly intervals using ultrasensitive quantitative PCR to detect Plasmodium infections. The study was conducted between May 2013 and July 2017. The investigators randomised 16 villages that had a total of 8,445 residents at the start of the study. Of these 8,445 residents, 4,135 (49%) residents living in 8 villages, plus an additional 288 newcomers to the villages, were randomised to receive early MDA; 3,790 out of the 4,423 (86%) participated in at least 1 MDA round, and 2,520 out of the 4,423 (57%) participated in all 3 rounds. The primary outcome, P. falciparum prevalence by month 3 (M3), fell by 92% (from 5.1% [171/3,340] to 0.4% [12/2,828]) in early MDA villages and by 29% (from 7.2% [246/3,405] to 5.1% [155/3,057]) in control villages. Over the following 9 months, the P. falciparum prevalence increased to 3.3% (96/2,881) in early MDA villages and to 6.1% (128/2,101) in control villages (adjusted incidence rate ratio 0.41 [95% CI 0.20 to 0.84]; p = 0.015). Individual protection was proportional to the number of completed MDA rounds. Of 221 participants with subclinical P. falciparum infections who participated in MDA and could be followed up, 207 (94%) cleared their infections, including 9 of 10 with artemisinin- and piperaquine-resistant infections. The DP MDAs were well tolerated; 6 severe adverse events were detected during the follow-up period, but none was attributable to the intervention.ConclusionsAdded to community-based basic malaria control measures, 3 monthly rounds of DP MDA reduced the incidence and prevalence of falciparum malaria over a 1-year period in areas affected by artemisinin resistance. P. falciparum infections returned during the follow-up period as the remaining infections spread and malaria was reintroduced from surrounding areas. Limitations of this study include a relatively small sample of villages, heterogeneity between villages, and mobility of villagers that may have limited the impact of the intervention. These results suggest that, if used as part of a comprehensive, well-organised, and well-resourced elimination programme, DP MDA can be a useful additional tool to accelerate malaria elimination.Trial registrationClinicalTrials.gov NCT01872702.