Vector Competence for Dengue-2 Viruses Isolated from Patients with Different Disease Severity.

Dynamics of dengue serotype 2 virus isolated from patients with different disease severity, namely flu-like classic dengue fever (DF) and dengue shock syndrome (DSS) were studied in its mosquito vector Aedes aegypti. We compared isolate infectivity and vector competence (VC) among thirty two A. aegypti-viral isolate pairs. Mosquito populations from high dengue incidence area exhibited overall greater VC than those from low dengue incidence area at 58.1% and 52.5%, respectively. On the other hand, the overall infection rates for the isolates ThNR2/772 (DF, 62.3%) and ThNR2/391 (DSS, 60.9%), were significantly higher than those for isolates ThNR2/406 (DF, 55.2%) and ThNR2/479 (DSS, 54.8%). These results suggest that the efficacy of dengue virus circulation was likely to vary according to the combination between the virus strains and origin of the mosquito strains, and this may have epidemiologic implications toward the incidence of flu-like classic dengue fever (DF) and dengue shock syndrome (DSS).

The durability of long-lasting insecticidal nets distributed to the households between 2009 and 2013 in Nepal.

BACKGROUND: Understanding and improving the durability of long-lasting insecticidal nets (LLINs) in the field are critical for planning future implementation strategies including behavioral change for care and maintenance. LLIN distribution at high coverage is considered to be one of the adjunctive transmission reduction strategies in Nepal's Malaria Strategic Plan 2014-2025. The main objective of this study was to assess the durability through assessment of community usage, physical integrity, residual bio-efficacy, and chemical retention in LLINs: Interceptor®, Yorkool®, and PermaNet ®2.0 which were used in Nepal during 2009 through 2013. METHODS: Assessments were conducted on random samples (n = 440) of LLINs from the eleven districts representing four ecological zones: Terai plain region (Kailali and Kanchanpur districts), outer Terai fluvial ecosystem (Surkhet, Dang, and Rupandhei districts), inner Terai forest ecosystem (Mahhothari, Dhanusa, and Illam districts), and Hills and river valley (Kavrepalanchock and Sindhupalchok districts). For each LLIN, fabric integrity in terms of proportionate hole index (pHI) and residual bio-efficacy were assessed. However, for chemical retention, a representative sample of 44 nets (15 Yorkool®, 10 Permanet®2.0, and 19 Interceptor®) was evaluated. Data were analyzed using descriptive statistics stratified by LLINs brand, districts, and duration of exposure. RESULTS: On average, duration of use of LLINs was shortest for the Yorkool® samples, followed by PermaNet® 2.0 and Interceptor® with median ages of 8.9 (IQR = 0.4), 23.8 (IQR = 3.2), and 50.1 (IQR = 3.2) months, respectively. Over 80% of field distributed Yorkool® and PermaNet® 2.0 nets were in good condition (pHI< 25) compared to Interceptor® (66%). Bio-efficacy analysis showed that average mortality rates of Interceptor and Yorkool were below World Health Organization (WHO) optimal effectiveness of ≥ 80% compared to 2-year-old PermaNet 2.0 which attained 80%. Chemical retention analysis was consistent with bio-efficacy results. CONCLUSION: This study shows that distribution of LLINs is effective for malaria control; however, serviceable life of LLINs should be considered in terms of waning residual bio-efficacy that warrants replacement. As an adjunctive malaria control tool, National Malaria Control Program of Nepal can benefit by renewing the distribution of LLINs in an appropriate time frame in addition to utilizing durable and effective LLINs.

Characterising residual malaria transmission in forested areas with low coverage of core vector control in central Viet Nam.

BACKGROUND: Despite great success in significantly reducing the malaria burden in Viet Nam over recent years, the ongoing presence of malaria vectors and Plasmodium infection in remote forest areas and among marginalised groups presents a challenge to reaching elimination and a threat to re-emergence of transmission. Often transmission persists in a population despite high reported coverage of long-lasting insecticidal nets (LLINs), the mainstay control method for malaria. To investigate what factors may contribute to this, a mixed-methods study was conducted in Son Thai commune, a community in south-central Viet Nam that has ongoing malaria cases despite universal LLIN coverage. A cross-sectional behavioural and net-coverage survey was conducted along with observations of net use and entomological collections in the village, farm huts and forest sites used by members of the community. RESULTS: Most community members owned a farm hut plot and 71.9% of adults aged 18+ years sometimes slept overnight in the farm hut, while one-third slept overnight in the forest. Ownership and use of nets in the village households was high but in the farm huts and forest was much lower; only 44.4% reported regularly using a bednet in the farm and 12.1% in the forest. No primary anopheline species were captured in the village, but Anopheles dirus (s.l.) (n = 271) and An. maculatus (s.l.) (n = 14) were captured as far as 4.5 km away in farm huts and forest. A high proportion of biting was conducted in the early evening before people were under nets. Entomological inoculation rates (EIR) of An. dirus (s.l.) were 17.8 and 25.3 infectious bites per person per year in the outdoor farm hut sites and forest, respectively, for Plasmodium falciparum and 25.3 in the forest sites for P. vivax. CONCLUSIONS: Despite high net coverage in the village, gaps in coverage and access appear in the farm huts and forest where risk of anopheline biting and parasite transmission is much greater. Since subsistence farming and forest activities are integral to these communities, new personal protection methods need to be explored for use in these areas that can ideally engage with the community, be durable, portable and require minimal behavioural change.

Correction to: Transmission risk beyond the village: entomological and human factors contributing to residual malaria transmission in an area approaching malaria elimination on the Thailand-Myanmar border.

Following publication of the original article [1], the authors advised of two errors present in the article: one concerning two author names and the other missing funding details.

Transmission risk beyond the village: entomological and human factors contributing to residual malaria transmission in an area approaching malaria elimination on the Thailand-Myanmar border.

BACKGROUND: A mixed methods study was conducted to look at the magnitude of residual malaria transmission (RMT) and factors contributing to low (< 1% prevalence), but sustained transmission in rural communities on the Thai-Myanmar border. METHODS: A cross-sectional behaviour and net survey, observational surveys and entomological collections in both villages and forested farm huts frequented by community members for subsistence farming practices were conducted. RESULTS: Community members frequently stayed overnight at subsistence farm huts or in the forest. Entomological collections showed higher biting rates of primary vectors in forested farm hut sites and in a more forested village setting compared to a village with clustered housing and better infrastructure. Despite high levels of outdoor biting, biting exposure occurred predominantly indoors, particularly for non-users of long-lasting insecticidal nets (LLINs). Risk of biting exposure was exacerbated by sub-optimal coverage of LLINs, particularly in subsistence farm huts and in the forest. Furthermore, early waking hours when people had left the safety of their nets coincided with peaks in biting in later morning hours. CONCLUSIONS: Entomological and epidemiological findings suggest drivers and modulators of sustained infection prevalence in the area to be: higher mosquito abundance in forested areas where LLINs were used less frequently or could not be used; late sleeping and waking times coinciding with peak biting hours; feeding preferences of Anopheles taking them away from contact with LLIN and indoor residual spraying (IRS), e.g. exophagy and zoophagy; non-use of LLIN and use of damaged/torn LLIN; high population movement across the border and into forested areas thereby increasing risk of exposure, decreasing use of protection and limiting access to healthcare; and, Plasmodium vivax predominance resulting in relapse(s) of previous infection. The findings highlight gaps in current intervention coverage beyond the village setting.

Molecular Identification of Enteroviruses from Cattle and Goat Feces and Environment in Thailand.

The identification and characterization of viruses of the genus Enterovirus in healthy and infected livestock, including cattle and goats, have been increasing. Enterovirus E (EV-E) and Enterovirus F (EV-F) are commonly found in cattle, whereas Enterovirus G (EV-G) is found in goats. In this study, molecular and phylogenetic analyses were performed to determine the prevalence of EVs in cattle and goat feces from Kanchanaburi Province, Thailand. The presence of EVs in water samples and the feces of other animals collected from the areas surrounding cattle and goat farms was also investigated. By use of 5'-untranslated region (5' UTR) real-time reverse transcription-PCR (RT-PCR), EVs were detected in 39.5% of cattle samples, 47% of goat samples, 35.3% of water samples, and one pool of chicken feces. Phylogenetic analysis revealed the presence of EV-E and EV-F in cattle, EV-E and EV-G in goats, and EV-F in water samples and chicken feces. Analysis of enteroviral VP1 sequences from cattle revealed that the EV-E genotypes circulating in the study region were EV-E1, with a possible new genotype that is closely related to EV-E2. Analysis of enteroviral VP1 sequences from goats suggested the circulation of EV-G5 and a possible new genotype that is closely related to EV-G20. Sequence analyses also suggested that although the VP1 sequences from goats were closely related to those of EV-G, which were considered porcine enterovirus sequences, their 5' UTRs form a separated cluster with sequences of sheep and goat origin, suggesting a new classification of the ovine/caprine-specific enterovirus group.IMPORTANCE Possible new EV-E and EV-G genotypes were identified for EVs detected in this study. The EV-E viruses were also successfully isolated from MDBK cells. The goat EV sequence analysis suggested the presence of an ovine/caprine-specific EV group that is different from EV-G of porcine origin. The significance of our research is that it identifies and characterizes possible novel EVs, thereby indicating that enteroviruses in animals are continually evolving. The facts that enteroviruses can persist in the environment, contaminate it for long periods, and be transmitted between animals raise serious concerns regarding this group of viruses as emerging livestock pathogens.

Evaluation of the GeneXpert MTB/RIF in patients with presumptive tuberculous meningitis.

BACKGROUND: Meningitis caused by Mycobacterium tuberculosis is a major cause of morbidity and mortality worldwide. We evaluated the performance of cerebrospinal fluid (CSF) testing with the GeneXpert MTB/RIF assay versus traditional approaches for diagnosing tuberculosis meningitis (TBM). METHODS: Patients were adults (n = 37) presenting with suspected TBM to the Hospital Nacional Dos de Mayo, Lima, Peru, during 12 months until 1st January 2015. Each participant had a single CSF specimen that was divided into aliquots that were concurrently tested for M. tuberculosis using GeneXpert, Ziehl-Neelsen smear and culture on solid and liquid media. Drug susceptibility testing used Mycobacteria Growth Indicator Tube (MGIT 960) and the proportions method. RESULTS: 81% (30/37) of patients received a final clinical diagnosis of TBM, of whom 63% (19/30, 95% confidence intervals, CI: 44-80%) were HIV-positive. 22% (8/37, 95%CI: 9.8-38%), of patients had definite TBM. Because definite TBM was defined by positivity in any laboratory test, all laboratory tests had 100% specificity. Considering the 30 patients who had a clinical diagnosis of TBM: diagnostic sensitivity was 23% (7/30, 95%CI: 9.9-42%) for GeneXpert and was the same for all culture results combined; considerably greater than 7% (2/30, 95%CI: 0.82-22%) for microscopy; whereas all laboratory tests had poor negative predictive values (20-23%). Considering only the 8 patients with definite TBM: diagnostic sensitivity was 88% (7/8, 95%CI: 47-100%) for GeneXpert; 75% (6/8, 95%CI: 35-97%) for MGIT culture or LJ culture; 50% (4/8, 95%CI 16-84) for Ogawa culture and 25% (2/8, 95%CI: 3.2-65%) for microscopy. GeneXpert and microscopy provided same-day results, whereas culture took 20-56 days. GeneXpert provided same-day rifampicin-susceptibility results, whereas culture-based testing took 32-71 days. 38% (3/8, 95%CI: 8.5-76%) of patients with definite TBM with data had evidence of drug-resistant TB, but 73% (22/30) of all clinically diagnosed TBM (definite, probable, and possible TBM) had no drug-susceptibility results available. CONCLUSIONS: Compared with traditional culture-based methods of CSF testing, GeneXpert had similar yield and faster results for both the detection of M. tuberculosis and drug-susceptibility testing. Including use of the GeneXpert has the capacity to improve the diagnosis of TBM cases.

Genetic variations in regions of bovine and bovine-like enteroviral 5'UTR from cattle, Indian bison and goat feces.

BACKGROUND: Bovine enteroviruses (BEV) are members of the genus Enterovirus in the family Picornaviridae. They are predominantly isolated from cattle feces, but also are detected in feces of other animals, including goats and deer. These viruses are found in apparently healthy animals, as well as in animals with clinical signs and several studies reported recently suggest a potential role of BEV in causing disease in animals. In this study, we surveyed the presence of BEV in domestic and wild animals in Thailand, and assessed their genetic variability. METHODS: Viral RNA was extracted from fecal samples of cattle, domestic goats, Indian bison (gaurs), and deer. The 5' untranslated region (5'UTR) was amplified by nested reverse transcription-polymerase chain reaction (RT-PCR) with primers specific to BEV 5'UTR. PCR products were sequenced and analyzed phylogenetically using the neighbor-joining algorithm to observe genetic variations in regions of the bovine and bovine-like enteroviral 5'UTR found in this study. RESULTS: BEV and BEV-like sequences were detected in the fecal samples of cattle (40/60, 67 %), gaurs (3/30, 10 %), and goats (11/46, 24 %). Phylogenetic analyses of the partial 5'UTR sequences indicated that different BEV variants (both EV-E and EV-F species) co-circulated in the domestic cattle, whereas the sequences from gaurs and goats clustered according to the animal species, suggesting that these viruses are host species-specific. CONCLUSIONS: Varieties of BEV and BEV-like 5'UTR sequences were detected in fecal samples from both domestic and wild animals. To our knowledge, this is the first report of the genetic variability of BEV in Thailand.

Distribution of selected healthcare resources for influenza pandemic response in Cambodia.

INTRODUCTION: Human influenza infection poses a serious public health threat in Cambodia, a country at risk for the emergence and spread of novel influenza viruses with pandemic potential. Prior pandemics demonstrated the adverse impact of influenza on poor communities in developing countries. Investigation of healthcare resource distribution can inform decisions regarding resource mobilization and investment for pandemic mitigation. METHODS: A health facility survey performed across Cambodia obtained data on availability of healthcare resources important for pandemic influenza response. Focusing on five key resources considered most necessary for treating severe influenza (inpatient beds, doctors, nurses, oseltamivir, and ventilators), resource distributions were analyzed at the Operational District (OD) and Province levels, refining data analysis from earlier studies. Resources were stratified by respondent type (hospital vs. District Health Office [DHO]). A summary index of distribution inequality was calculated using the Gini coefficient. Indices for local spatial autocorrelation were measured at the OD level using geographical information system (GIS) analysis. Finally, a potential link between socioeconomic status and resource distribution was explored by mapping resource densities against poverty rates. RESULTS: Gini coefficient calculation revealed variable inequality in distribution of the five key resources at the Province and OD levels. A greater percentage of the population resides in areas of relative under-supply (28.5%) than over-supply (21.3%). Areas with more resources per capita showed significant clustering in central Cambodia while areas with fewer resources clustered in the northern and western provinces. Hospital-based inpatient beds, doctors, and nurses were most heavily concentrated in areas of the country with the lowest poverty rates; however, beds and nurses in Non-Hospital Medical Facilities (NHMF) showed increasing concentrations at higher levels of poverty. CONCLUSIONS: There is considerable heterogeneity in healthcare resource distribution across Cambodia. Distribution mapping at the local level can inform policy decisions on where to stockpile resources in advance of and for reallocation in the event of a pandemic. These findings will be useful in determining future health resource investment, both for pandemic preparedness and for general health system strengthening, and provide a foundation for future analyses of equity in health services provision for pandemic mitigation planning in Cambodia.

Malaria situation in the Greater Mekong Subregion.

The epidemiology of malaria in the Greater Mekong Subregion is complex and rapidly evolving. Malaria control and elimination efforts face a daunting array of challenges including multidrug-resistant parasites. This review presents secondary data collected by the national malaria control programs in the six countries between 1998 and 2010 and examines trends over the last decade. This data has a number of limitations: it is derived exclusively from public sector health facilities; falciparum-specific and then pan-specific rapid diagnostic tests were introduced during the period under review; and, recently there has been a massive increase in case detection capability as a result of increased funding. It therefore requires cautious interpretation. A series of maps are presented showing trends in incidence, mortality and proportion of cases caused by Plasmodium falciparum over the last decade. A brief overview of institutional and implementation arrangements, historical background, demographics and key issues affecting malaria epidemiology is provided for each country. National malaria statistics for 2010 are presented and their robustness discussed in terms of the public sector's share of cases and other influencing factors such as inter-country variations in risk stratification, changes in diagnostic approach and immigration. Targets are presented for malaria control and where appropriate for elimination. Each country's artemisinin resistance status is described. The epidemiological trends presented reflect the improvement in the malaria situation, however the true malaria burden is as yet unknown. There is a need for continuing strengthening and updating of surveillance and response systems.

A randomized comparison of dihydroartemisinin-piperaquine and artesunate-amodiaquine combined with primaquine for radical treatment of vivax malaria in Sumatera, Indonesia.

BACKGROUND: A high prevalence of chloroquine-resistant Plasmodium vivax in Indonesia has shifted first-line treatment to artemisinin-based combination therapies, combined with primaquine (PQ) for radical cure. Which combination is most effective and safe remains to be established. METHODS: We conducted a prospective open-label randomized comparison of 14 days of PQ (0.25 mg base/kg) plus either artesunate-amodiaquine (AAQ + PQ) or dihydroartemisinin-piperaquine (DHP + PQ) for the treatment of uncomplicated monoinfection P. vivax malaria in North Sumatera, Indonesia. Patients were randomized and treatments were given without prior testing for G6PD status. The primary outcome was parasitological failure at day 42. Patients were followed up to 1 year. RESULTS: Between December 2010 and April 2012, 331 patients were included. After treatment with AAQ + PQ, recurrent infection occurred in 0 of 167 patients within 42 days and in 15 of 130 (11.5%; 95% confidence interval [CI], 6.6%-18.3%) within a year. With DHP + PQ, this was 1 of 164 (0.6%; 95% CI, 0.01%-3.4%) and 13 of 143 (9.1%; 95% CI, 4.9%-15.0%), respectively (P > .2). Intravascular hemolysis occurred in 5 patients, of which 3 males were hemizygous for the G6PD-Mahidol mutation. Minor adverse events were more frequent with AAQ + PQ. CONCLUSIONS: In North Sumatera, Indonesia, AAQ and DHP, both combined with PQ, were effective for blood-stage parasite clearance of uncomplicated P. vivax malaria. Both treatments were safe, but DHP + PQ was better tolerated. CLINICAL TRIALS REGISTRATION: NCT01288820.

An analysis of health system resources in relation to pandemic response capacity in the Greater Mekong Subregion.

BACKGROUND: There is increasing perception that countries cannot work in isolation to militate against the threat of pandemic influenza. In the Greater Mekong Subregion (GMS) of Asia, high socio-economic diversity and fertile conditions for the emergence and spread of infectious diseases underscore the importance of transnational cooperation. Investigation of healthcare resource distribution and inequalities can help determine the need for, and inform decisions regarding, resource sharing and mobilisation. METHODS: We collected data on healthcare resources deemed important for responding to pandemic influenza through surveys of hospitals and district health offices across four countries of the GMS (Cambodia, Lao PDR, Thailand, Vietnam). Focusing on four key resource types (oseltamivir, hospital beds, ventilators, and health workers), we mapped and analysed resource distributions at province level to identify relative shortages, mismatches, and clustering of resources. We analysed inequalities in resource distribution using the Gini coefficient and Theil index. RESULTS: Three quarters of the Cambodian population and two thirds of the Laotian population live in relatively underserved provinces (those with resource densities in the lowest quintile across the region) in relation to health workers, ventilators, and hospital beds. More than a quarter of the Thai population is relatively underserved for health workers and oseltamivir. Approximately one fifth of the Vietnamese population is underserved for beds and ventilators. All Cambodian provinces are underserved for at least one resource. In Lao PDR, 11 percent of the population is underserved by all four resource items. Of the four resources, ventilators and oseltamivir were most unequally distributed. Cambodia generally showed higher levels of inequalities in resource distribution compared to other countries. Decomposition of the Theil index suggests that inequalities result principally from differences within, rather than between, countries. CONCLUSIONS: There is considerable heterogeneity in healthcare resource distribution within and across countries of the GMS. Most inequalities result from within countries. Given the inequalities, mismatches, and clustering of resources observed here, resource sharing and mobilization in a pandemic scenario could be crucial for more effective and equitable use of the resources that are available in the GMS.

Development of a resource modelling tool to support decision makers in pandemic influenza preparedness: The AsiaFluCap Simulator.

BACKGROUND: Health care planning for pandemic influenza is a challenging task which requires predictive models by which the impact of different response strategies can be evaluated. However, current preparedness plans and simulations exercises, as well as freely available simulation models previously made for policy makers, do not explicitly address the availability of health care resources or determine the impact of shortages on public health. Nevertheless, the feasibility of health systems to implement response measures or interventions described in plans and trained in exercises depends on the available resource capacity. As part of the AsiaFluCap project, we developed a comprehensive and flexible resource modelling tool to support public health officials in understanding and preparing for surges in resource demand during future pandemics. RESULTS: The AsiaFluCap Simulator is a combination of a resource model containing 28 health care resources and an epidemiological model. The tool was built in MS Excel© and contains a user-friendly interface which allows users to select mild or severe pandemic scenarios, change resource parameters and run simulations for one or multiple regions. Besides epidemiological estimations, the simulator provides indications on resource gaps or surpluses, and the impact of shortages on public health for each selected region. It allows for a comparative analysis of the effects of resource availability and consequences of different strategies of resource use, which can provide guidance on resource prioritising and/or mobilisation. Simulation results are displayed in various tables and graphs, and can also be easily exported to GIS software to create maps for geographical analysis of the distribution of resources. CONCLUSIONS: The AsiaFluCap Simulator is freely available software (http://www.cdprg.org) which can be used by policy makers, policy advisors, donors and other stakeholders involved in preparedness for providing evidence based and illustrative information on health care resource capacities during future pandemics. The tool can inform both preparedness plans and simulation exercises and can help increase the general understanding of dynamics in resource capacities during a pandemic. The combination of a mathematical model with multiple resources and the linkage to GIS for creating maps makes the tool unique compared to other available software.

Health system resource gaps and associated mortality from pandemic influenza across six Asian territories.

BACKGROUND: Southeast Asia has been the focus of considerable investment in pandemic influenza preparedness. Given the wide variation in socio-economic conditions, health system capacity across the region is likely to impact to varying degrees on pandemic mitigation operations. We aimed to estimate and compare the resource gaps, and potential mortalities associated with those gaps, for responding to pandemic influenza within and between six territories in Asia. METHODS AND FINDINGS: We collected health system resource data from Cambodia, Indonesia (Jakarta and Bali), Lao PDR, Taiwan, Thailand and Vietnam. We applied a mathematical transmission model to simulate a "mild-to-moderate" pandemic influenza scenario to estimate resource needs, gaps, and attributable mortalities at province level within each territory. The results show that wide variations exist in resource capacities between and within the six territories, with substantial mortalities predicted as a result of resource gaps (referred to here as "avoidable" mortalities), particularly in poorer areas. Severe nationwide shortages of mechanical ventilators were estimated to be a major cause of avoidable mortalities in all territories except Taiwan. Other resources (oseltamivir, hospital beds and human resources) are inequitably distributed within countries. Estimates of resource gaps and avoidable mortalities were highly sensitive to model parameters defining the transmissibility and clinical severity of the pandemic scenario. However, geographic patterns observed within and across territories remained similar for the range of parameter values explored. CONCLUSIONS: The findings have important implications for where (both geographically and in terms of which resource types) investment is most needed, and the potential impact of resource mobilization for mitigating the disease burden of an influenza pandemic. Effective mobilization of resources across administrative boundaries could go some way towards minimizing avoidable deaths.

Directly observed therapy with primaquine to reduce the recurrence rate of plasmodium vivax infection along the Thai-Myanmar border.

This study was carried out from April 2005 to June 2006 to evaluate the recurrence of P. vivax malaria infection in relation to drug compliance along the Thai-Myanmar border in Ratchaburi, Thailand. Ninety-two patients with vivax malaria were sequentially assigned to 2 groups. Both groups received a standard dose of chloroquine (total dose = 2.5 g) for 3 days and primaquine (total dose = 210 mg) for 14 days. The experimental group received a full course of treatment using daily directly observed therapy (DOT) while subjects in the control group were given the medication with necessary instructions to take as self-administered therapy (SAT). Patients were followed up for 3 months on Days 14, 21, 28, 60 and 90. Five of 46 patients from the SAT group had recurrence of malaria on Days 21, 44, 60, 72 and 87. Recurrence was not observed among patients in the DOT group. Survival analysis also showed significant differences between the SAT and DOT groups (p <0.05). The study suggests patient compliance with the 14-day primaquine treatment with DOT improve the outcome of .vivax malaria treatment.

The impact of human reservoir of malaria at a community-level on individual malaria occurrence in a low malaria transmission setting along the Thai-Myanmar border.

BACKGROUND: The probability of contracting malaria in a given individual is determined not only by the individual's characteristics, but also the ecological factors that characterize the level of human-vector contact in the population. Examination of the relationship between "individual" and "supra-individual" variables over time is important for understanding the local malaria epidemiology. This is essential for planning effective intervention strategies specifically for each location. METHODS: A retrospective cohort study was conducted, which followed a community-cohort of about 3,500 residents in seven hamlets along the Thai-Myanmar border between 1999 and 2006. Potential malaria determinants measured at different levels (temporal variables, individual variables, and hamlet variables) were incorporated into multilevel models to estimate their effects on an individual's risk of malaria attack. RESULTS: The monthly minimum temperature was significantly associated with the seasonal variation of malaria risk. An individual risk of malaria attack decreased by about 50% during the period that active surveillance was conducted; an additional 15% and 25% reduction of Plasmodium falciparum and Plasmodium vivax incidence, respectively, was observed after the use of artesunate-mefloquine combination therapy (ACT) for treatment of P. falciparum. Male children (age < 16 years old) were at highest risk of both P. falciparum and P. vivax attack. An increase in the hamlet's incidence of P. falciparum and P. vivax by 1 per 100 persons in a previous month resulted in 1.14 and 1.34 times increase in the risk of P. falciparum and P. vivax, respectively, among individuals in a particular hamlet. CONCLUSION: In a small area with low malaria transmission intensity, the variation in mosquito abundance is relatively similar across the residential areas; incidence of malaria between hamlets, which reflects the community level of human infectious reservoirs, is an important predictor for the malaria risk among individuals within these hamlets. Therefore, local malaria control strategies should focus on interventions that aim to reduce the gametocyte carriage in the population, such as early detection and treatment programmes and the use of ACT for P. falciparum.

Longitudinal study of Plasmodium falciparum and Plasmodium vivax in a Karen population in Thailand.

BACKGROUND: Clinical case treatment of malaria infections where Plasmodium falciparum and Plasmodium vivax are sympatric has achieved effective reductions in P. falciparum prevalence and incidence rates, but has been less successful for P. vivax. The high transmissibility of P. vivax and its capacity to relapse have been suggested to make it a harder parasite species to control. METHODS: A clinical malaria case treatment programme was carried out over a decade in a Karen community composed of seven hamlets on the Thai-Myanmar border. RESULTS: From 1994 to 2004, prevalence rates of both P. falciparum and P. vivax decreased by 70-90% in six of the seven study hamlets, but were unchanged in one hamlet. Overall, incidence rates decreased by 72% and 76% for P. falciparum and P. vivax respectively over the period 1999-2004. The age-incidence and prevalence curves suggested that P. vivax was more transmissible than P. falciparum despite a greater overall burden of infection with P. falciparum. Male gender was associated with increased risk of clinical presentation with either parasite species. Children (< 15 years old) had an increased risk of presenting with P. vivax but not P. falciparum. CONCLUSION: There was a considerable reduction in incidence rates of both P. vivax and P. falciparum over a decade following implementation of a case treatment programme. The concern that intervention methods would inadvertently favour one species over another, or even lead to an increase in one parasite species, does not appear to be fulfilled in this case.