A cohort study of Plasmodium falciparum infection dynamics in Western Kenya Highlands.

Background: The Kenyan highlands were malaria-free before the 1910s, but a series of malaria epidemics have occurred in the highlands of western Kenya since the 1980s. Longitudinal studies of the genetic structure, complexity, infection dynamics, and duration of naturally acquired Plasmodium falciparum infections are needed to facilitate a comprehensive understanding of malaria epidemiology in the complex Kenyan highland eco-epidemiological systems where malaria recently expanded, as well as the evaluation of control measures.

Methods: We followed a cohort of 246 children residing in 3 villages at altitudes 1430 - 1580 m in western Kenya.

Possible interruption of malaria transmission, highland Kenya, 2007-2008.

Highland areas where malaria transmission is unstable are targets for malaria elimination because transmission decreases to low levels during the dry season. In highland areas of Kipsamoite and Kapsisiywa, Kenya (population approximately 7,400 persons), annual household indoor residual spraying with a synthetic pyrethroid was performed starting in 2005, and artemether/lumefantrine was implemented as first-line malaria treatment in October 2006. During April 2007-March 2008, no microscopy-confirmed cases of malaria occurred at the sites.

High prevalence of asymptomatic plasmodium falciparum infections in a highland area of western Kenya: a cohort study.

Background: Transmission of malaria in an area of hypoendemicity in the highlands of western Kenya is not expected to lead to rapid acquisition of immunity to malaria. However, the subpopulation of individuals with asymptomatic Plasmodium falciparum infection may play a significant role as an infection reservoir and should be considered in malaria-control programs. Determination of the spatiotemporal dynamics of asymptomatic subpopulations provides an opportunity to estimate the epidemiological importance of this group to malaria transmission.

Microscopy underestimates the frequency of Plasmodium falciparum infection in symptomatic individuals in a low transmission highland area.

In an area with unstable malaria transmission, detection of Plasmodium falciparum infection in 379 symptomatic individuals was assessed by microscopy and three polymerase chain reaction (PCR) methodologies. P. falciparum infection was detected in 25% of patients by microscopy, 37% by nested PCR, 41% by merozoite surface protein-2 (MSP-2) PCR, and 45% by a ligase detection reaction-fluorescent microsphere assay (LDR-FMA).

Molecular epidemiology of drug-resistant malaria in western Kenya highlands.

Background: Since the late 1980s a series of malaria epidemics has occurred in western Kenya highlands. Among the possible factors that may contribute to the highland malaria epidemics, parasite resistance to antimalarials has not been well investigated.

Methods: Using parasites from highland and lowland areas of western Kenya, we examined key mutations associated with Plasmodium falciparum resistance to sulfadoxine - pyrimethamine and chloroquine, including dihydrofolate reductase (pfdhfr) and dihydropteroate synthetase (pfdhps), chloroquine resistance transporter gene (pfcrt), and multi-drug resistance gene 1 (pfmdr1).

Plasmodium falciparum genetic diversity in western Kenya highlands.

The present study examined the genetic diversity and population structure of Plasmodium falciparum in western Kenya by analyzing the polymorphism of 12 microsatellite loci and two antigen loci. Malaria in highland areas is unstable and epidemic whereas malaria in lowland areas is endemic. Transmission intensity and malaria prevalence are substantially lower in the highlands than in the lowlands.

Amplified fragment length polymorphism mapping of quantitative trait loci for malaria parasite susceptibility in the yellow fever mosquito Aedes aegypti.

The yellow fever mosquito Aedes aegypti has been the subject of extensive genetic research due to its medical importance and the ease with which it can be manipulated in the laboratory. A molecular genetic linkage map was constructed using 148 amplified fragment length polymorphism (AFLP) and six single-strand conformation polymorphism (SSCP) markers. Eighteen AFLP primer combinations were used to genotype two reciprocal F2 segregating populations.

Quantitative trait loci controlling refractoriness to Plasmodium falciparum in natural Anopheles gambiae mosquitoes from a malaria-endemic region in western Kenya.

Natural anopheline populations exhibit much variation in ability to support malaria parasite development, but the genetic mechanisms underlying this variation are not clear. Previous studies in Mali, West Africa, identified two quantitative trait loci (QTL) in Anopheles gambiae mosquitoes that confer refractoriness (failure of oocyst development in mosquito midguts) to natural Plasmodium falciparum parasites. We hypothesize that new QTL may be involved in mosquito refractoriness to malaria parasites and that the frequency of natural refractoriness genotypes may be higher in the basin region of Lake Victoria, East Africa, where malaria transmission intensity and parasite genetic diversity are among the highest in the world.

Fitness consequences of Anopheles gambiae population hybridization.

Background: The use of transgenic mosquitoes with parasite inhibiting genes has been proposed as an integral strategy to control malaria transmission. However, release of exotic transgenic mosquitoes will bring in novel alleles along with parasite-inhibiting genes that may have unknown effects on native populations. Thus it is necessary to study the effects and dynamics of fitness traits in native mosquito populations in response to the introduction of novel genes.

Mapping of chromosomal regions influencing immunological responses to gastrointestinal nematode infections in mice.

This paper reports the results of a genome-wide search for quantitative trait loci (QTL) influencing immunological responses to infection with the gastro-intestinal nematode parasite Heligmosomoides polygyrus in an F2 population created by crossing the resistant SWR and the susceptible CBA inbred mouse strains. Following infections, intestinal granuloma score at post mortem, mucosal mast cell protease 1, and IgE and IgG1 titres were recorded. The susceptible CBA mice had significantly higher IgG1, but significantly lower IgE, mucosal mast cell protease 1 and granuloma scores than SWR mice.

Chromosomal regions controlling resistance to gastro-intestinal nematode infections in mice.

Quantitative trait loci (QTL) associated with resistance to an intestinal worm in a well-defined murine model are described. These have been identified in an F(2) population derived from resistant (SWR) and susceptible (CBA) parental mouse strains infected with the gastro-intestinal nematode parasite Heligmosomoides polygyrus. Seven QTL located on six chromosomes are described, associated with components of the complex host response and the differential regulation of parasite survival and reproduction.