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Background: The East African highlands are fringe regions between stable and unstable malaria transmission. What factors contribute to the heterogeneity of malaria exposure on different spatial scales within larger foci has not been extensively studied. In a comprehensive, community-based cross-sectional survey an attempt was made to identify factors that drive the macro- and micro epidemiology of malaria in a fringe region using parasitological and serological outcomes. Methods: A large cross-sectional survey including 17,503 individuals was conducted across all age groups in a 100 km2 area in the Western Kenyan highlands of Rachuonyo South district. Households were geo-located and prevalence of malaria parasites and malaria-specific antibodies were determined by PCR and ELISA. Household and individual risk-factors were recorded. Geographical characteristics of the study area were digitally derived using high-resolution satellite images. Results: Malaria antibody prevalence strongly related to altitude (1350-1600 m, p < 0.001). A strong negative association with increasing altitude and PCR parasite prevalence was found. Parasite carriage was detected at all altitudes and in all age groups; 93.2 % (2481/2663) of malaria infections were apparently asymptomatic. Malaria parasite prevalence was associated with age, bed net use, house construction features, altitude and topographical wetness index. Antibody prevalence was associated with all these factors and distance to the nearest water body. Conclusion: Altitude was a major driver of malaria transmission in this study area, even across narrow altitude bands. The large proportion of asymptomatic parasite carriers at all altitudes and the age-dependent acquisition of malaria antibodies indicate stable malaria transmission; the strong correlation between current parasite carriage and serological markers of malaria exposure indicate temporal stability of spatially heterogeneous transmission. [ABSTRACT FROM AUTHOR]

Background: Monitoring and evaluation of malaria programmes may require a combination of approaches to detect any effects of control. This is particularly true at lower transmission levels where detecting both infection and exposure to infection will provide additional evidence of any change. This paper describes use of three transmission metrics to explore the malaria epidemiology in the highlands of western Kenya. Methods: A malariometric survey was conducted in June 2009 in two highland districts, Kisii and Rachuonyo South, Nyanza Province, Kenya using a cluster design. Enumeration areas were used to sample 46 clusters from which 12 compounds were randomly sampled. Individuals provided a finger-blood sample to assess malaria infection (rapid diagnostic test, PCR) and exposure (anti-Plasmodium falciparum MSP-1 antibodies) and a questionnaire was administered to record household factors and assess use of vector control interventions. Results: Malaria prevalence infection rates were 3.0 % (95 % CI 2.2–4.2 %) by rapid diagnostic test (RDT) and 8.5 % (95 % CI 7.0–10.4 %) by PCR and these ranged from 0–13.1 to 0–14.8 % between clusters for RDT and PCR, respectively. Seroprevalence was 36.8 % (95 % CI 33.9–39.8) ranging from 18.6 to 65.8 %. Both RDT and PCR prevalences were highest in children aged 5–10 years but the proportion of infections that were sub-patent was highest in those between 15 and 20 years of age (78.1 %, 95 % CI 63.0–93.3 %) and those greater than 20 years (73.3 %, 95 % CI 64.5– 81.9 %). Those reporting both indoor residual spraying (IRS) in their home and use of bed nets had lower exposure to malaria compared to those who reported using IRS or bed nets alone. Conclusions: In this highland site in western Kenya malaria transmission was low, but highly heterogeneous. To accurately characterize the true extent of malaria transmission, more sensitive and complementary metrics such as PCR or serology are required in addition to the standard microscopy and/or RDTs that are routinely used. This is likely to be the case in other low endemicity settings. [ABSTRACT FROM AUTHOR]

Background: Motivated by the success in malaria control that was documented over the last decade Ethiopia is aiming at malaria elimination by 2020 in selected districts. It is currently unknown if asymptomatic, submicroscopic malaria parasite carriage may form a hurdle to achieve elimination. The elimination effort may further be complicated by possible glucose-6 phosphate dehydrogenase (G6PD) deficiency which would hinder the use of 8-aminoquinolines in the elimination efforts. Method: In February 2014 a community-based cross-sectional survey was conducted in Malo, southwest Ethiopia. Finger-prick blood samples (n = 555) were tested for presence of Plasmodium falciparum and Plasmodium vivax with microscopy, rapid diagnostic test (RDT), and nested polymerase chain reaction (nPCR). Multiplicity of P. falciparum infections was determined based on genotyping the polymorphic merozoite surface protein-2 (MSP-2) gene. Individuals were also genotyped for mutations in the gene that produces G6PD. Results: All study participants were malaria infection negative by microscopy and RDT. Nested PCR revealed P. falciparum mono-infection in 5.2% (29/555), P. vivax mono-infection in 4.3% (24/555) and mixed infection in 0.2% (1/555) of individuals. All parasitemic individuals were afebrile (axillary temperature <37.5°C). None of the study participants carried mutations for the G6PD African A-(202GA) and Mediterranean (563CT) variants. All infections, except one, were single-clone infection by MSP-2 genotyping. Conclusion: The detection of a substantial number of subpatent malaria infections in an apparently asymptomatic population without evidence for malaria transmission by conventional diagnostics raises questions about the path to malaria elimination. It is currently unknown how important these infections are for sustaining malaria transmission in the study sites. The absence of G6PD deficiency indicates that 8-aminoquinolines may be safely deployed to accelerate elimination initiatives. [ABSTRACT FROM AUTHOR]

Background: Informing and evaluating malaria control efforts relies on knowledge of local transmission dynamics. Serological and molecular tools have demonstrated great sensitivity to quantify transmission intensity in low endemic settings where the sensitivity of traditional methods is limited. Filter paper blood spots are commonly used a source of both DNA and antibodies. To enhance the operational practicability of malaria surveys, a method is presented for combined DNA extraction and antibody elution. Methods: Filter paper blood spots were collected as part of a large cross-sectional survey in the Kenyan highlands. DNA was extracted using a saponin/chelex method. The eluate of the first wash during the DNA extraction process was used for antibody detection and compared with previously validated antibody elution procedures. Antibody elution efficiency was assessed by total IgG ELISA for malaria antigens apical membrane antigen-1 (AMA-1) and merozoite-surface protein-1 (MSP-142). The sensitivity of nested 18S rRNA and cytochrome b PCR assays and the impact of doubling filter paper material for PCR sensitivity were determined. The distribution of cell material and antibodies throughout filter paper blood spots were examined using luminescent and fluorescent reporter assays. Results: Antibody levels measured after the combined antibody/DNA extraction technique were strongly correlated to those measured after standard antibody elution (p < 0.0001). Antibody levels for both AMA-1 and MSP-142 were generally slightly lower (11.3-21.4%) but age-seroprevalence patterns were indistinguishable. The proportion of parasite positive samples ranged from 12.9% to 19.2% in the different PCR assays. Despite strong agreement between outcomes of different PCR assays, none of the assays detected all parasite-positive individuals. For all assays doubling filter paper material for DNA extraction increased sensitivity. The concentration of cell and antibody material was not homogenously distributed throughout blood spots. Conclusion: Combined DNA extraction and antibody elution is an operationally attractive approach for high throughput assessment of cumulative malaria exposure and current infection prevalence in endemic settings. Estimates of antibody prevalence are unaffected by the combined extraction and elution procedure. The choice of target gene and the amount and source of filter paper material for DNA extraction can have a marked impact on PCR sensitivity. [ABSTRACT FROM AUTHOR]

Background: Malaria transmission is highly heterogeneous in most settings, resulting in the formation of recognizable malaria hotspots. Targeting these hotspots might represent a highly efficacious way of controlling or eliminating malaria if the hotspots fuel malaria transmission to the wider community. Methods/design: Hotspots of malaria will be determined based on spatial patterns in age-adjusted prevalence and density of antibodies against malaria antigens apical membrane antigen-1 and merozoite surface protein-1. The community effect of interventions targeted at these hotspots will be determined. The intervention will comprise larviciding, focal screening and treatment of the human population, distribution of long-lasting insecticide-treated nets and indoor residual spraying. The impact of the intervention will be determined inside and up to 500 m outside the targeted hotspots by PCR-based parasite prevalence in cross-sectional surveys, malaria morbidity by passive case detection in selected facilities and entomological monitoring of larval and adult Anopheles populations. Discussion: This study aims to provide direct evidence for a community effect of hotspot-targeted interventions. The trial is powered to detect large effects on malaria transmission in the context of ongoing malaria interventions. Follow-up studies will be needed to determine the effect of individual components of the interventions and the cost-effectiveness of a hotspot-targeted approach, where savings made by reducing the number of compounds that need to receive interventions should outweigh the costs of hotspot-detection. [ABSTRACT FROM AUTHOR]

An abstract of the article "Extended malaria parasite clearance time in African children following artemisinincombination therapy enhances transmission to Anopheles mosquitoes," by Khalid B. Beshir, Patrick Sawa, Chris J. Drakeley, Amrish Y. Baidjoe and colleagues is presented.

Background: It is controversial to what degree α(+)-thalassaemia protects against episodes of uncomplicated malaria and febrile disease due to infections other than Plasmodium., Methods: In Tanzania, in children aged 6-60 months and height-for-age z-score < -1.5 SD (n = 612), rates of fevers due to malaria and other causes were compared between those with heterozygous or homozygotes α(+)-thalassaemia and those with a normal genotype, using Cox regression models that accounted for multiple events per child., Results: The overall incidence of malaria was 3.0/child-year (1, 572/526 child-years); no differences were found in malaria rates between genotypes (hazard ratios, 95% CI: 0.93, 0.82-1.06 and 0.91, 0.73-1.14 for heterozygotes and homozygotes respectively, adjusted for baseline factors that were predictive for outcome). However, this association strongly depended on age: among children aged 6-17 months, those with α(+)-thalassaemia experienced episodes more frequently than those with a normal genotype (1.30, 1.02-1.65 and 1.15, 0.80-1.65 for heterozygotes and homozygotes respectively), whereas among their peers aged 18-60 months, α(+)-thalassaemia protected against malaria (0.80, 0.68-0.95 and 0.78, 0.60-1.03; p-value for interaction 0.001 and 0.10 for hetero- and homozygotes respectively). No effect was observed on non-malarial febrile episodes., Conclusions: In this population, the association between α(+)-thalassaemia and malaria depends on age. Our data suggest that protection by α(+)-thalassaemia is conferred by more efficient acquisition of malaria-specific immunity.