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BACKGROUND: Artemisinin resistance in Plasmodium falciparum threatens global malaria elimination efforts. To contain and then eliminate artemisinin resistance in Eastern Myanmar a network of community-based malaria posts was instituted and targeted mass drug administration (MDA) with dihydroartemisinin-piperaquine (three rounds at monthly intervals) was conducted. The prevalence of artemisinin resistance during the elimination campaign (2013-2019) was characterized. METHODS: Throughout the six-year campaign Plasmodium falciparum positive blood samples from symptomatic patients and from cross-sectional surveys were genotyped for mutations in kelch-13-a molecular marker of artemisinin resistance. RESULT: The program resulted in near elimination of falciparum malaria. Of 5162 P. falciparum positive blood samples genotyped, 3281 (63.6%) had K13 mutations. The prevalence of K13 mutations was 73.9% in 2013 and 64.4% in 2019. Overall, there was a small but significant decline in the proportion of K13 mutants (p

BackgroundDespite notable progress in the control and prevention of malaria in the Horn of Africa, the disease continues to cause significant morbidity and mortality in various regions of Ethiopia, and elsewhere in the region. The transmission of malaria is affected by genetic, sociocultural, and ecological factors. Lare is an Ethiopian district adjacent to the Ethio-South Sudan border, in Gambella region. The region currently has the highest prevalence of malaria in Ethiopia. This study assesses the burden and spatiotemporal patterns of disease transmission, including the effect of climatic factors on the occurrence of malaria, across an international border crossing. This understanding can assist in crafting informed programmatic and policy decisions for interventions.MethodsThis study was conducted in Lare district, Southwest Ethiopia, a temperate zone. A retrospective descriptive analysis was conducted using clinical service data collected between 2011 and 2021 from the 9 health facilities of the district. Both clinically diagnosed patients and those identified using microscopy and rapid diagnostic testing (RDT) were included in the study. Additionally, climate data was incorporated into analyses. Examples of analyses include malaria burden, positivity rate, incidence, species frequency, and an ANOVA to assess inter-annual case number and meteorological factor variation.ResultsBetween 2011 and 2021, a total of 96,616 suspected malaria cases were tested by microscopy or RDT, and 39,428 (40.8%) of these cases were reported as positive. There were 1276 patients admitted with 22 deaths recorded. There were further more significant fluctuations in positivity rates across years, the highest being 74.5% in 2021. Incidence varied from 18.0% in 2011 to 151.6% in 2016. The malaria parasite species most detected was Plasmodium falciparum, followed by a smaller proportion of Plasmodium vivax. The greatest proportions of P. falciparum cases were observed in 2018 and 2019, at 97.4% and 97.0% prevalence, respectively. There was significant seasonal variation in case number, the highest observed in July through September of each year. Climatic conditions of annual rainfall, temperature and humidity favored the increment of malaria cases from June until October.ConclusionThe study shows that the burden, i.e. morbidity and mortality (with fluctuating patterns) of malaria are still significant public health problems and can pose serious consequences in the district. This has implication for cross-border malaria transmission risk due to considerable border crossings. The predominant cause of the disease is P. falciparum, which causes severe complications in patients. The district has to prepare to deal with such complications for better patient care and outcomes.

BackgroundMass drug administration (MDA) with primaquine (PQ) is being considered for accelerating Plasmodium vivax elimination in remaining active foci. This study aimed to determine the acceptability of MDA with PQ in malaria endemic villages in a malarious setting in the South of Thailand undergoing MDA with PQ.MethodsA cross-sectional mixed-methods approach was conducted in seven malaria endemic villages where MDA with PQ was implemented. The data were collected from community villagers and health workers using structured questionnaires, in-depth interviews, and focus group discussions. Descriptive statistics and logistic regression models were used for quantitative data analysis. Thematic analysis was applied for qualitative data.ResultsAmong a total of 469 participants from the MDA villages, 293 participants were eligible for MDA with PQ and 79.86% (234) completed 14-days of PQ. The logistic regressions indicated that males (adjusted odds ratio: 2.52 [95% confidence interval: 1.33-4.81]) and those who are farmers (2.57 [1.12-5.90]) were most likely to participate in the MDA. Among 293 participants in the post-MDA study, 74.06% had originally agreed to participate in the MDA with PQ while 25.94% had originally reported not wanting to participate in the MDA. Of those who originally reported being willing to participate in the MDA, 71.23% followed through with participation in the first or second round. Conversely, 93.24% of those who originally reported not being willing to participate in the MDA did in fact participate in the MDA. Factors contributing to higher odds of agreeing to participate and following through with participation included being male (1.98 [1.06-3.69]) and correctly responding that malaria is preventable (2.32 [1.01-5.35]) with some differences by village. Five key themes emerged from the qualitative analyses: concern about side effects from taking PQ; disbelief that malaria could be eliminated in this setting; low overall concern about malaria infections; misunderstandings about malaria; and a general need to tailor public health efforts for this unique context.ConclusionWhile the reported likelihood of participating in MDA was high in this setting, actual follow-through was relatively moderate, partially because of eligibility (roughly 71% of those in the follow-up survey who originally agreed to participate actually followed through with participation). One of the largest concerns among study participants was PQ-related side effects-and these concerns likely heavily influenced participant adherence to the MDA. The results of this study can be used to tailor future MDAs, or other public health interventions, in this and potentially other similar settings.

BackgroundThe collection and utilization of surveillance data is essential in monitoring progress towards achieving malaria elimination, in the timely response to increases in malaria case numbers and in the assessment of programme functioning. This paper describes the surveillance activities used by the malaria elimination task force (METF) programme which operates in eastern Myanmar, and provides an analysis of data collected from weekly surveillance, case investigations, and monitoring and evaluation of programme performance.MethodsThis retrospective analysis was conducted using data collected from a network of 1250 malaria posts operational between 2014 and 2021. To investigate changes in data completeness, malaria post performance, malaria case numbers, and the demographic details of malaria cases, summary statistics were used to compare data collected over space and time.ResultsIn the first 3 years of the METF programme, improvements in data transmission routes resulted in a 18.9% reduction in late reporting, allowing for near real-time analysis of data collected at the malaria posts. In 2020, travel restrictions were in place across Karen State in response to COVID-19, and from February 2021 the military coup in Myanmar resulted in widescale population displacement. However, over that period there has been no decline in malaria post attendance, and the majority of consultations continue to occur within 48 h of fever onset. Case investigations found that 43.8% of cases travelled away from their resident village in the 3 weeks prior to diagnosis and 36.3% reported never using a bed net whilst sleeping in their resident village, which increased to 72.2% when sleeping away from their resident village. Malaria post assessments performed in 82.3% of the METF malaria posts found malaria posts generally performed to a high standard.ConclusionsSurveillance data collected by the METF programme demonstrate that despite significant changes in the context in which the programme operates, malaria posts have remained accessible and continue to provide early diagnosis and treatment contributing to an 89.3% decrease in Plasmodium falciparum incidence between 2014 and 2021.

BackgroundHuman mobility behaviour modelling plays an essential role in the understanding and control of the spread of contagious diseases by limiting the contact among individuals, predicting the spatio-temporal evolution of an epidemic and inferring migration patterns. It informs programmatic and policy decisions for effective and efficient intervention. The objective of this research is to assess the human mobility pattern and analyse its implication for malaria disease epidemiology.MethodsIn this study, human mobility patterns in Benishangul-Gumuz and Gambella regions in Western Ethiopia were explored based on a cellular network mobility parameter (e.g., handover rate) via real world data. Anonymized data were retrieved for mobile active users with mobility related information. The data came from anonymous traffic records collected from all the study areas. For each cell, the necessary mobility parameter data per hour, week and month were collected. A scale factor was computed to change the mobility parameter value to the human mobility pattern. Finally, the relative human mobility probability for each scenario was estimated. MapInfo and Matlab softwares were used for visualization and analysis purposes. Hourly travel patterns in the study settings were compared with hourly malaria mosquito vector feeding behaviour.ResultsHeterogeneous human movement patterns were observed in the two regions with some areas showing typically high human mobility. Furthermore, the number of people entering into the two study regions was high during the highest malaria transmission season. Two peaks of hourly human movement, 8:00 to 9:00 and 16:00 to 18:00, emerged in Benishangul-Gumuz region while 8:00 to 10:00 and 16:00 to 18:00 were the peak hourly human mobility time periods in Gambella region. The high human movement in the night especially before midnight in the two regions may increase the risk of getting mosquito bite particularly by early biters depending on malaria linked human behaviour of the population.ConclusionsHigh human mobility was observed both within and outside the two regions. The population influx and efflux in these two regions is considerably high. This may specifically challenge the transition from malaria control to elimination. The daily mobility pattern is worth considering in the context of malaria transmission. In line with this malaria related behavioural patterns of humans need to be properly addressed.

BackgroundWith the goal for malaria elimination in Thailand set for 2024, increased coverage and utilization of bed net, especially insecticide-treated net (ITN) or long-lasting insecticidal net (LLIN) is a key strategy. This study aims to provide the necessary information about bed net ownership and utilization among the population at risk of malaria living along the Thai-Myanmar border in Tak province.MethodsA cross-sectional study was conducted using a mixed-method approach in 331 households from 5 hamlets in the villages of the Thai-Myanmar border. The research tools included a questionnaire, bed net inspection, and semi-structured interviews. Logistic regression was used to explore the sociodemographic factors associated with bed net utilization. The qualitative analysis employed a thematic analysis approach.ResultsThis survey found that 98.5% of households had at least one bed net per household, and 74.3% had at least one ITN/LLIN. However, only 30.8% of households reached the standard policy set by the Minister of Public Health of one ITN/LLINs per two persons. Most residents used bed net (92.1% used in the previous night and 80.9% used every day). For those using bed nets, however, 61.9% used ITNs or LLINs the night before and 53.1% used them every day. Nonetheless, the usage rates of bed nets (any type) in the previous night among children and pregnant women were high, reaching 95.3% and 90.0%, respectively. Seven explanatory variables showed statistically significant associations with bed net use every day, including: "not staying overnight in the forest or the field", "sleeping pattern based on gender", "sufficient numbers of bed nets to cover all sleeping spaces", "preference for free bed nets", "age", "gender", and "SES score" showed statistically significant association with bed net use every day. The major reasons for the regular use of bed nets in both household and the forest were to prevent mosquito biting. The reasons for not using bednets in the household were discomfort feelings from heat, perception of unnecessity due to low mosquito density, whereas the reason for not using bed nets in the forest was inconvenience.ConclusionDespite that overall coverage and usage of bed nets was high, only one third reached the standard level specified by the policy. Overnight in the forest, the dissatisfaction with the quality of free bed nets, insufficient number of bed nets, sleeping alone, male gender, age more than 10 years, low socioeconomic status, discomfort from heat, perception of no benefits of bed nets due to low mosquito density, and inconvenience were factors influencing bed net use. Maintaining high coverage and utility rate of bed nets should be a priority for the malaria high-risk population.

BackgroundMalaria reactive case detection is the testing and, if positive, treatment of close contacts of index cases. It is included in national malaria control programmes of countries in the Greater Mekong Subregion to accelerate malaria elimination. Yet the value of reactive case detection in the control and elimination of malaria remains controversial because of the low yield, limited evidence for impact, and high demands on resources.MethodsData from the epidemiological assessments of large mass drug administration (MDA) studies in Myanmar, Vietnam, Cambodia and Laos were analysed to explore malaria infection clustering in households. The proportion of malaria positive cases among contacts screened in a hypothetical reactive case detection programme was then determined. The parasite density thresholds for rapid diagnostic test (RDT) detection was assumed to be > 50/µL (50,000/mL), for dried-blood-spot (DBS) based PCR > 5/µL (5000/mL), and for ultrasensitive PCR (uPCR) with a validated limit of detection at 0.0022/µL (22/mL).ResultsAt baseline, before MDA, 1223 Plasmodium infections were detected by uPCR in 693 households. There was clustering of Plasmodium infections. In 637 households with asymptomatic infections 44% (278/637) had more than one member with Plasmodium infections. In the 132 households with symptomatic infections, 65% (86/132) had more than one member with Plasmodium infections. At baseline 4% of households had more than one Plasmodium falciparum infection, but three months after MDA no household had more than one P. falciparum infected member. Reactive case detection using DBS PCR would have detected ten additional cases in six households, and an RDT screen would have detected five additional cases in three households among the 169 households with at least one RDT positive case. This translates to 19 and 9 additional cases identified per 1000 people screened, respectively. Overall, assuming all febrile RDT positive patients would seek treatment and provoke reactive case detection using RDTs, then 1047 of 1052 (99.5%) Plasmodium infections in these communities would have remained undetected.ConclusionReactive case detection in the Greater Mekong subregion is predicted to have a negligible impact on the malaria burden, but it has substantial costs in terms of human and financial resources.

BackgroundMany public health interventions lead to disruption or decrease of transmission, providing a beneficial effect for people in the population regardless of whether or not they individually participate in the intervention. This protective benefit has been referred to as a herd or community effect and is dependent on sufficient population participation. In practice, public health interventions are implemented at different spatial scales (i.e., at the village, district, or provincial level). Populations, however defined (i.e., neighbourhoods, villages, districts) are frequently connected to other populations through human movement or travel, and this connectedness can influence potential herd effects.MethodsThe impact of a public health intervention (mass drug administration for malaria) was modelled, for different levels of connectedness between populations that have similar disease epidemiology (e.g., two nearby villages which have similar baseline malaria incidences and similar malaria intervention measures), or between populations of varying disease epidemiology (e.g., two nearby villages which have different baseline malaria incidences and/or malaria intervention measures).ResultsThe overall impact of the interventions deployed could be influenced either positively (adding value to the intervention) or negatively (reducing the impact of the intervention) by how much the intervention units are connected with each other (e.g., how frequent people go to the other village or town) and how different the disease intensity between them are. This phenomenon is termed the "assembly effect", and it is a meta-population version of the more commonly understood "herd effect".ConclusionsThe connectedness of intervention units or populations is an important factor to be considered to achieve success in public health interventions that could provide herd effects. Appreciating the assembly effect can improve the cost-effective strategies for global disease elimination projects.

BackgroundMalaria is heterogeneously distributed across landscapes. Human population movement (HPM) could link sub-regions with varying levels of transmission, leading to the persistence of disease even in very low transmission settings. Malaria along the Thai-Myanmar border has been decreasing, but remains heterogeneous. This study aimed to measure HPM, associated predictors of travel, and HPM correlates of self-reported malaria among people living within malaria hotspots.Methods526 individuals from 279 households in two malaria hotspot areas were included in a prospective observational study. A baseline cross-sectional study was conducted at the beginning, recording both individual- and household-level characteristics. Individual movement and travel patterns were repeatedly observed over one dry season month (March) and one wet season month (May). Descriptive statistics, random effects logistic regressions, and logistic regressions were used to describe and determine associations between HPM patterns, individual-, household-factors, and self-reported malaria.ResultsTrips were more common in the dry season. Malaria risk was related to the number of days doing outdoor activities in the dry season, especially trips to Myanmar, to forest areas, and overnight trips. Trips to visit forest areas were more common among participants aged 20-39, males, individuals with low income, low education, and especially among individuals with forest-related occupations. Overnight trips were more common among males, and individual with forest-related occupations. Forty-five participants reported having confirmed malaria infection within the last year. The main place of malaria blood examination and treatment was malaria post and malaria clinic, with participants usually waiting for 2-3 days from onset fever to seeking diagnosis. Individuals using bed nets, living in houses with elevated floors, and houses that received indoor residual spraying in the last year were less likely to report malaria infection.ConclusionAn understanding of HPM and concurrent malaria dynamics is important for consideration of targeted public health interventions. Furthermore, diagnosis and treatment centres must be capable of quickly diagnosing and treating infections regardless of HPM. Coverage of diagnosis and treatment centres should be broad, maintained in areas bordering malaria hotspots, and available to all febrile individuals.

BackgroundArtemisinin resistance, linked to polymorphisms in the Kelch gene on chromosome 13 of Plasmodium falciparum (k13), has outpaced containment efforts in South East Asia. For national malaria control programmes in the region, it is important to establish a surveillance system which includes monitoring for k13 polymorphisms associated with the clinical phenotype.MethodsBetween February and December 2013, parasite clearance was assessed in 35 patients with uncomplicated P. falciparum treated with artesunate monotherapy followed by 3-day ACT in an isolated area on the Myanmar-Thai border with relatively low artemisinin drug pressure. Molecular testing for k13 mutations was performed on dry blood spots collected on admission.ResultsThe proportion of k13 mutations in these patients was 41.7%, and only 5 alleles were detected: C580Y, I205T, M476I, R561H, and F446I. Of these, F446I was the most common, and was associated with a longer parasite clearance half-life (median) 4.1 (min-max 2.3-6.7) hours compared to 2.5 (min-max 1.6-8.7) in wildtype (p = 0·01). The prevalence of k13 mutant parasites was much lower than the proportion of k13 mutants detected 200 km south in a much less remote setting where the prevalence of k13 mutants was 84% with 15 distinct alleles in 2013 of which C580Y predominated.ConclusionsThis study provides evidence of artemisinin resistance in a remote part of eastern Myanmar. The prevalence of k13 mutations as well as allele diversity varies considerably across short distances, presumably because of historical patterns of artemisinin use and population movements.

BACKGROUND:The number of Plasmodium falciparum malaria cases around the world has decreased substantially over the last 15 years, but with the spread of resistance against anti-malarial drugs and insecticides, this decline may not continue. There is an urgent need to consider alternative, accelerated strategies to eliminate malaria in countries like Lao PDR, where there are a few remaining endemic areas. A deterministic compartmental modelling tool was used to develop an integrated strategy for P. falciparum elimination in the Savannakhet province of Lao PDR. The model was designed to include key aspects of malaria transmission and integrated control measures, along with a user-friendly interface. RESULTS:Universal coverage was the foundation of the integrated strategy, which took the form of the deployment of community health workers who provided universal access to early diagnosis, treatment and long-lasting insecticidal nets. Acceleration was included as the deployment of three monthly rounds of mass drug administration targeted towards high prevalence villages, with the addition of three monthly doses of the RTS,S vaccine delivered en masse to the same high prevalence sub-population. A booster dose of vaccine was added 1 year later. The surveillance-as-intervention component of the package involved the screening and treatment of individuals entering the simulated population. CONCLUSIONS:In this modelling approach, the sequential introduction of a series of five available interventions in an integrated strategy was predicted to be sufficient to stop malaria transmission within a 3-year period. These interventions comprised universal access to early diagnosis and adequate treatment, improved access to long-lasting insecticidal nets, three monthly rounds of mass drug administration together with RTS,S vaccination followed by a booster dose of vaccine, and screening and treatment of imported cases.

BackgroundReactive case detection is an approach that has been proposed as a tool for malaria elimination in low-transmission settings. It is an intuitively justified approach based on the concept of space-time clustering of malaria cases. When an index malaria clinical case is detected, it triggers reactive screening and treatment in the index house and neighbouring houses. However, the efficacy of this approach at varying screening radii and malaria prevalence remains ill defined.MethodsData were obtained from a detailed demographic and geographic surveillance study in four villages on the Myanmar-Thailand border. Clinical cases were recorded at village malaria clinics and were linked back to patients' residencies. These data were used to simulate the efficacy of reactive case detection for clinical cases using rapid diagnostic tests (RDT). Simulations took clinical cases in a given month and tabulated the number of cases that would have been detected in the following month at varying screening radii around the index houses. Simulations were run independently for both falciparum and vivax malaria. Each simulation of a reactive case detection effort was run in comparison with a strategy using random selection of houses for screening.ResultsIn approximately half of the screenings for falciparum and 10% for vivax it would have been impossible to detect any malaria cases regardless of the screening strategy because the screening would have occurred during times when there were no cases. When geographically linked cases were present in the simulation, reactive case detection would have only been successful at detecting most malaria cases using larger screening radii (150-m radius and above). At this screening radius and above, reactive case detection does not perform better than random screening of an equal number of houses in the village. Screening within very small radii detects only a very small proportion of cases, but despite this low performance is better than random screening with the same sample size.ConclusionsThe results of these simulations indicate that reactive case detection for clinical cases using RDTs has limited ability in halting transmission in regions of low and unstable transmission. This is linked to high spatial heterogeneity of cases, acquisition of malaria infections outside the village, as well missing asymptomatic infections. When cases are few and sporadic, reactive case detection would result in major time and budgetary losses.

Falciparum malaria persists in hard-to-reach areas or demographic groups that are missed by conventional healthcare systems but could be reached by trained community members in a malaria post (MP). The main focus of a MP is to provide uninterrupted and rapid access to rapid diagnostic tests (RDTs) and artemisinin-based combination therapy (ACT) too all inhabitants of a village. RDTs allow trained community members to perform malaria diagnosis accurately and prescribe appropriate treatment, reducing as much as possible any delay between the onset of fever and treatment. Early treatment with ACT and with a low-dose of primaquine prevents further transmission from human to mosquito. A functioning MP represents an essential component of any malaria elimination strategy. Implementing large-scale, high-coverage, community-based early diagnosis and treatment through MPs requires few technological innovations but relies on a very well structured organization able to train, supervise and supply MPs, to monitor activity and to perform strict malaria surveillance.

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.

BackgroundEndemic malaria in Thailand continues to only exist along international borders. This pattern is frequently attributed to importation of malaria from surrounding nations. A microgeographical approach was used to investigate malaria cases in a study village along the Thailand-Myanmar border.MethodsThree mass blood surveys were conducted during the study period (July and December 2011, and May 2012) and were matched to a cohort-based demographic surveillance system. Blood slides and filter papers were taken from each participant. Slides were cross-verified by an expert microscopist and filter papers were analysed using nested PCR. Cases were then mapped to households and analysed using spatial statistics. A risk factor analysis was done using mixed effects logistic regression.ResultsIn total, 55 Plasmodium vivax and 20 Plasmodium falciparum cases (out of 547 participants) were detected through PCR, compared to six and two (respectively) cases detected by field microscopy. The single largest risk factor for infection was citizenship. Many study participants were ethnic Karen people with no citizenship in either Thailand or Myanmar. This subpopulation had over eight times the odds of malaria infection when compared to Thai citizens. Cases also appeared to cluster near a major drainage system and year-round water source within the study village.ConclusionThis research indicates that many cases of malaria remain undiagnosed in the region. The spatial and demographic clustering of cases in a sub-group of the population indicates either transmission within the Thai village or shared exposure to malaria vectors outside of the village. While it is possible that malaria is imported to Thailand from Myanmar, the existence of undetected infections, coupled with an ecological setting that is conducive to malaria transmission, means that indigenous transmission could also occur on the Thai side of the border. Improved, timely, and active case detection is warranted.

Abstract Background Malaria within the Greater Mekong sub-region is extremely heterogeneous. While China and Thailand have been relatively successful in controlling malaria, Myanmar continues to see high prevalence. Coupled with the recent emergence of artemisinin-resistant malaria along the Thai-Myanmar border, this makes Myanmar an important focus of malaria within the overall region. However, accurate epidemiological data from Myanmar have been lacking, in part because of ongoing and emerging conflicts between the government and various ethnic groups. Here the results are reported from a risk analysis of malaria slide positivity in a conflict zone along the China-Myanmar border. Methods Surveys were conducted in 13 clinics and hospitals around Laiza City, Myanmar between April 2011 and October 2012. Demographic, occupational and educational information, as well as malaria infection history, were collected. Logistic models were used to assess risk factors for slide positivity. Results Age patterns in Plasmodium vivax infections were younger than those with Plasmodium falciparum. Furthermore, males were more likely than females to have falciparum infections. Patients who reported having been infected with malaria during the previous year were much more likely to have a current vivax infection. During the second year of the study, falciparum infections among soldiers increased signficiantly. Conclusions These results fill some knowledge gaps with regard to risk factors associated with malaria slide positivity in this conflict region of north-eastern Myanmar. Since epidemiological studies in this region have been rare or non-existent, studies such as the current are crucial for understanding the dynamic nature of malaria in this extremely heterogeneous epidemiological landscape.

Abstract Background Drug and multidrug-resistant Plasmodium falciparum malaria has existed in Thailand for several decades. Furthermore, Thailand serves as a sentinel for drug-resistant malaria within the Greater Mekong sub-region. However, the drug resistance situation is highly dynamic, changing quickly over time. Here parasite in vitro drug sensitivity is reported for artemisinin derivatives, mefloquine, chloroquine and quinine, across Thailand. Methods Blood was drawn from patients infected with P. falciparum in seven sentinel provinces along Thai international borders with Cambodia, Myanmar, Laos, and Malaysia. In vitro parasite sensitivity was tested using the World Health Organization’s microtest (mark III) (between 1994 and 2002) and the histidine-rich protein-2 (HRP2)-based enzyme-linked immunosorbent assay (in 2010). Following World Health Organization protocol, at least 30 isolates were collected for each province and year represented in this study. Where possible, t-tests were used to test for significant differences. Results There appears to be little variation across study sites with regard to parasite sensitivity to chloroquine. Quinine resistance appears to have been rising prior to 1997, but has subsequently decreased. Mefloquine sensitivity appears high across the provinces, especially along the north-western border with Myanmar and the eastern border with Cambodia. Finally, the data suggest that parasite sensitivity to artemisinin and its derivatives is significantly higher in provinces along the north-western border with Myanmar. Conclusions Parasite sensitivity to anti-malarials in Thailand is highly variable over time and largely mirrors official drug use policy. The findings with regard to reduced sensitivity to artemisinin derivatives are supported by recent reports of reduced parasite clearance associated with artemisinin. This trend is alarming since artemisinin is considered the last defence against malaria. Continued surveillance in Thailand, along with increased collaboration and surveillance across the entire Greater Mekong sub-region, is clearly warranted.

Abstract Background Drug and multidrug-resistant Plasmodium falciparum malaria has existed in Thailand for several decades. Furthermore, Thailand serves as a sentinel for drug-resistant malaria within the Greater Mekong sub-region. However, the drug resistance situation is highly dynamic, changing quickly over time. Here parasite in vitro drug sensitivity is reported for artemisinin derivatives, mefloquine, chloroquine and quinine, across Thailand. Methods Blood was drawn from patients infected with P. falciparum in seven sentinel provinces along Thai international borders with Cambodia, Myanmar, Laos, and Malaysia. In vitro parasite sensitivity was tested using the World Health Organization’s microtest (mark III) (between 1994 and 2002) and the histidine-rich protein-2 (HRP2)-based enzyme-linked immunosorbent assay (in 2010). Following World Health Organization protocol, at least 30 isolates were collected for each province and year represented in this study. Where possible, t-tests were used to test for significant differences. Results There appears to be little variation across study sites with regard to parasite sensitivity to chloroquine. Quinine resistance appears to have been rising prior to 1997, but has subsequently decreased. Mefloquine sensitivity appears high across the provinces, especially along the north-western border with Myanmar and the eastern border with Cambodia. Finally, the data suggest that parasite sensitivity to artemisinin and its derivatives is significantly higher in provinces along the north-western border with Myanmar. Conclusions Parasite sensitivity to anti-malarials in Thailand is highly variable over time and largely mirrors official drug use policy. The findings with regard to reduced sensitivity to artemisinin derivatives are supported by recent reports of reduced parasite clearance associated with artemisinin. This trend is alarming since artemisinin is considered the last defence against malaria. Continued surveillance in Thailand, along with increased collaboration and surveillance across the entire Greater Mekong sub-region, is clearly warranted.

Background: The number of Plasmodium falciparum malaria cases around the world has decreased substantially over the last 15 years, but with the spread of resistance against anti-malarial drugs and insecticides, this decline may not continue. There is an urgent need to consider alternative, accelerated strategies to eliminate malaria in countries like Lao PDR, where there are a few remaining endemic areas. A deterministic compartmental modelling tool was used to develop an integrated strategy for P. falciparum elimination in the Savannakhet province of Lao PDR. The model was designed to include key aspects of malaria transmission and integrated control measures, along with a user-friendly interface. Results: Universal coverage was the foundation of the integrated strategy, which took the form of the deployment of community health workers who provided universal access to early diagnosis, treatment and long-lasting insecticidal nets. Acceleration was included as the deployment of three monthly rounds of mass drug administration targeted towards high prevalence villages, with the addition of three monthly doses of the RTS,S vaccine delivered en masse to the same high prevalence sub-population. A booster dose of vaccine was added 1 year later. The surveillance-asintervention component of the package involved the screening and treatment of individuals entering the simulated population. Conclusions: In this modelling approach, the sequential introduction of a series of five available interventions in an integrated strategy was predicted to be sufficient to stop malaria transmission within a 3-year period. These interventions comprised universal access to early diagnosis and adequate treatment, improved access to long-lasting insecticidal nets, three monthly rounds of mass drug administration together with RTS,S vaccination followed by a booster dose of vaccine, and screening and treatment of imported cases. [ABSTRACT FROM AUTHOR]

Background Nested PCR is considered a sensitive and specific method for detecting malaria parasites and is especially useful in epidemiological surveys. However, the preparation of DNA templates for PCR is often time-consuming and costly. Methods A simplified PCR method was developed to directly use a small blood filter paper square (2 × 2 mm) as the DNA template after treatment with saponin. This filter paper-based nested PCR method (FP-PCR) was compared to microscopy and standard nested PCR with DNA extracted by using a Qiagen DNA mini kit from filter paper blood spots of 204 febrile cases. The FP-PCR technique was further applied to evaluate malaria infections in 1,708 participants from cross-sectional epidemiological surveys conducted in Myanmar and Thailand. Results The FP-PCR method had a detection limit of ~0.2 parasites/μl blood, estimated using cultured Plasmodium falciparum parasites. With 204 field samples, the sensitivity of the FP-PCR method was comparable to that of the standard nested PCR method, which was significantly higher than that of microscopy. Application of the FP-PCR method in large cross-sectional studies conducted in Myanmar and Thailand detected 1.9% (12/638) and 6.2% (66/1,070) asymptomatic Plasmodium infections, respectively, as compared to the detection rates of 1.3% (8/638) and 0.04% (4/1,070) by microscopy. Conclusion This FP-PCR method was much more sensitive than microscopy in detecting Plasmodium infections. It drastically increased the detection sensitivity of asymptomatic infections in cross-sectional surveys conducted in Thailand and Myanmar, suggesting that this FP-PCR method has a potential for future applications in malaria epidemiology studies. [ABSTRACT FROM AUTHOR]

Background Malaria within the Greater Mekong sub-region is extremely heterogeneous. While China and Thailand have been relatively successful in controlling malaria, Myanmar continues to see high prevalence. Coupled with the recent emergence of artemisinin-resistant malaria along the Thai-Myanmar border, this makes Myanmar an important focus of malaria within the overall region. However, accurate epidemiological data from Myanmar have been lacking, in part because of ongoing and emerging conflicts between the government and various ethnic groups. Here the results are reported from a risk analysis of malaria slide positivity in a conflict zone along the China-Myanmar border. Methods Surveys were conducted in 13 clinics and hospitals around Laiza City, Myanmar between April 2011 and October 2012. Demographic, occupational and educational information, as well as malaria infection history, were collected. Logistic models were used to assess risk factors for slide positivity. Results Age patterns in Plasmodium vivax infections were younger than those with Plasmodium falciparum. Furthermore, males were more likely than females to have falciparum infections. Patients who reported having been infected with malaria during the previous year were much more likely to have a current vivax infection. During the second year of the study, falciparum infections among soldiers increased signficiantlyConclusions These results fill some knowledge gaps with regard to risk factors associated with malaria slide positivity in this conflict region of north-eastern Myanmar. Since epidemiological studies in this region have been rare or non-existent, studies such as the current are crucial for understanding the dynamic nature of malaria in this extremely heterogeneous epidemiological landscape. [ABSTRACT FROM AUTHOR]