Yaw Afrane

Insecticide-treated net (ITN) ownership, usage, and malaria transmission in the highlands of western Kenya

BackgroundInsecticide-treated bed nets (ITNs) are known to be highly effective in reducing malaria morbidity and mortality. However, usage varies among households, and such variations in actual usage may seriously limit the potential impact of nets and cause spatial heterogeneity on malaria transmission. This study examined ITN ownership and underlying factors for among-household variation in use, and malaria transmission in two highland regions of western Kenya.MethodsCross-sectional surveys were conducted on ITN ownership (possession), compliance (actual usage among those who own ITNs), and malaria infections in occupants of randomly sampled houses in the dry and the rainy seasons of 2009.ResultsDespite ITN ownership reaching more than 71%, compliance was low at 56.3%. The compliance rate was significantly higher during the rainy season compared with the dry season (62% vs. 49.6%). Both malaria parasite prevalence (11.8% vs. 5.1%) and vector densities (1.0 vs.0.4 female/house/night) were significantly higher during the rainy season than during the dry season. Other important factors affecting the use of ITNs include: a household education level of at least primary school level, significantly high numbers of nuisance mosquitoes, and low indoor temperatures. Malaria prevalence in the rainy season was about 30% lower in ITN users than in non-ITN users, but this percentage was not significantly different during the dry season.ConclusionIn malaria hypo-mesoendemic highland regions of western Kenya, the gap between ITNownership and usage is generally high with greater usage recorded during the high transmission season. Because of the low compliance among those who own ITNs, there is a need to sensitize households on sustained use of ITNs in order to optimize their role as a malaria control tool.

Changing Patterns of Malaria Epidemiology between 2002 and 2010 in Western Kenya: The Fall and Rise of Malaria

Background The impact of insecticide treated nets (ITNs) on reducing malaria incidence is shown mainly through data collection from health facilities. Routine evaluation of long-term epidemiological and entomological dynamics is currently unavailable. In Kenya, new policies supporting the provision of free ITNs were implemented nationwide in June 2006. To evaluate the impacts of ITNs on malaria transmission, we conducted monthly surveys in three sentinel sites with different transmission intensities in western Kenya from 2002 to 2010. Methods and Findings Longitudinal samplings of malaria parasite prevalence in asymptomatic school children and vector abundance in randomly selected houses were undertaken monthly from February 2002. ITN ownership and usage surveys were conducted annually from 2004 to 2010. Asymptomatic malaria parasite prevalence and vector abundances gradually decreased in all three sites from 2002 to 2006, and parasite prevalence reached its lowest level from late 2006 to early 2007. The abundance of the major malaria vectors, Anopheles funestus and An. gambiae, increased about 5–10 folds in all study sites after 2007. However, the resurgence of vectors was highly variable between sites and species. By 2010, asymptomatic parasite prevalence in Kombewa had resurged to levels recorded in 2004/2005, but the resurgence was smaller in magnitude in the other sites. Household ITN ownership was at 50–70% in 2009, but the functional and effective bed net coverage in the population was estimated at 40.3%, 49.4% and 28.2% in 2010 in Iguhu, Kombewa, and Marani, respectively. Conclusion The resurgence in parasite prevalence and malaria vectors has been observed in two out of three sentinel sites in western Kenya despite a high ownership of ITNs. The likely factors contributing to malaria resurgence include reduced efficacy of ITNs, insecticide resistance in mosquitoes and lack of proper use of ITNs. These factors should be targeted to avoid further resurgence of malaria transmission.

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. METHODS Monthly parasitological surveys were undertaken for a cohort of 246 schoolchildren over 12 months. The prevalence of P. falciparum infection among 2,611 blood samples was analyzed by both microscopy and polymerase chain reaction, and infection durations were determined. RESULTS Infection prevalence and duration (range, 1-12 months) decreased with age and altitude. The prevalence was high among pooled blood samples recovered from children aged 5-9 years (34.4%) and from those aged 10-14 years (34.1%) but was significantly lower among blood samples obtained from older children (9.1%). The prevalence decreased from 52.4% among pooled blood samples from children living at an altitude of approximately 1,430 m to 23.3% among pooled samples from children living at an altitude of 1,580 m. CONCLUSIONS The prevalence of asymptomatic P. falciparum infection was high, with polymerase chain reaction analysis detecting a significantly greater number of infections, compared with microscopy. Our results are consistent with gradual acquisition of immunity with increasing age upon repeated infection, and they also show that the risk of malaria transmission is highly heterogeneous in the highland area. The results provide strong support for targeted malaria-control interventions.

Deforestation and Vectorial Capacity of Anopheles gambiae Giles Mosquitoes in Malaria Transmission, Kenya

One-sentence summary for table of contents: Land use changes are affecting malaria transmission in this region.

Comparative Transcriptome Analyses of Deltamethrin-Resistant and -Susceptible Anopheles gambiae Mosquitoes from Kenya by RNA-Seq

Malaria causes more than 300 million clinical cases and 665,000 deaths each year, and the majority of the mortality and morbidity occurs in sub-Saharan Africa. Due to the lack of effective vaccines and wide-spread resistance to antimalarial drugs, mosquito control is the primary method of malaria prevention and control. Currently, malaria vector control relies on the use of insecticides, primarily pyrethroids. The extensive use of insecticides has imposed strong selection pressures for resistance in the mosquito populations. Consequently, resistance to pyrethroids in Anopheles gambiae, the main malaria vector in sub-Saharan Africa, has become a major obstacle for malaria control. A key element of resistance management is the identification of resistance mechanisms and subsequent development of reliable resistance monitoring tools. Field-derived An. gambiae from Western Kenya were phenotyped as deltamethrin-resistant or -susceptible by the standard WHO tube test, and their expression profile compared by RNA-seq. Based on the current annotation of the An. gambiae genome, a total of 1,093 transcripts were detected as significantly differentially accumulated between deltamethrin-resistant and -susceptible mosquitoes. These transcripts are distributed over the entire genome, with a large number mapping in QTLs previously linked to pyrethorid resistance, and correspond to heat-shock proteins, metabolic and transport functions, signal transduction activities, cytoskeleton and others. The detected differences in transcript accumulation levels between resistant and susceptible mosquitoes reflect transcripts directly or indirectly correlated with pyrethroid resistance. RNA-seq data also were used to perform a de-novo Cufflinks assembly of the An. gambiae genome.

Genetic structure of Plasmodium falciparum populations between lowland and highland sites and antimalarial drug resistance in Western Kenya

Human travel to malaria endemic lowlands from epidemic highlands has been shown to increase the risk of malaria infections in the highlands. In order to gain insight on the impact of human travel, we examined prevalence, genetic variability and population genetic structure of Plasmodium falciparum in asymptomatic children from one highland site and three surrounding malaria endemic lowland sites in Western Kenya, using multilocus microsatellite genotyping. We further analyzed the frequencies of mutations at the genes conferring resistance to chloroquine and sulfadoxine-pyrimethamine. We found a significant decrease in malaria prevalence in the highland site from 2006 to 2007, 1 year after the introduction of the artemisinin-based combination therapy as first-line treatment for uncomplicated malaria and the scale-up of insecticide-treated bed nets. Population genetic diversity, measured by the number of observed and effective microsatellite alleles and Neis unbiased genetic diversity, was high and comparable for both highland and lowland populations. Analysis of molecular variance did not detect a significant genetic structure across highland and lowland regions. Similarly, mutations at key antimalarial-resistance codons of the pfcrt, pfmdr1, pfdhfr and pfdhps genes were found at comparable high frequencies in all four sites. High level of gene flow and lack of significant genetic structure in malaria parasites between highland and lowland areas suggest the importance of human travel in shaping parasite population structure.

Alternative splicing of the Anopheles gambiae Dscam gene in diverse Plasmodium falciparum infections

BackgroundIn insects, including Anopheles mosquitoes, Dscam (Down syndrome cell adhesion molecule) appears to be involved in phagocytosis of pathogens, and shows pathogen-specific splice-form expression between divergent pathogen (or parasite) types (e.g. between bacteria and Plasmodium or between Plasmodium berghei and Plasmodium falciparum). Here, data are presented from the first study of Dscam expression in response to genetic diversity within a parasite species.MethodsIn independent field and laboratory studies, a measure of Dscam splice-form diversity was compared between mosquitoes fed on blood that was free of P. falciparum to mosquitoes exposed to either single or mixed genotype infections of P. falciparum.ResultsSignificant increases in Anopheles gambiae Dscam (AgDscam) receptor diversity were observed in parasite-exposed mosquitoes, but only weak evidence that AgDscam diversity rises further upon exposure to mixed genotype parasite infections was found. Finally, a cluster of AgDscam exon 4 variants that become especially common during Plasmodium invasion was identified.ConclusionsWhile the data clearly indicate that AgDscam diversity increases with P. falciparum exposure, they do not suggest that AgDscam diversity rises further in response to increased parasite diversity.

Molecular epidemiology of drug-resistant malaria in western Kenya highlands

BackgroundSince 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.MethodsUsing 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).ResultsWe found that >70% of samples harbored 76T pfcrt mutations and over 80% of samples harbored quintuple mutations (51I/59R/108N pfdhfr and 437G/540E pfdhps) in both highland and lowland samples. Further, we did not detect significant difference in the frequencies of these mutations between symptomatic and asymptomatic malaria volunteers, and between highland and lowland samples.ConclusionThese findings suggest that drug resistance of malaria parasites in the highlands could be contributed by the mutations and their high frequencies as found in the lowland. The results are discussed in terms of the role of drug resistance as a driving force for malaria outbreaks in the highlands.

Habitat stability and occurrences of malaria vector larvae in western Kenya highlands

BackgroundAlthough the occurrence of malaria vector larvae in the valleys of western Kenya highlands is well documented, knowledge of larval habitats in the uphill sites is lacking. Given that most inhabitants of the highlands actually dwell in the uphill regions, it is important to develop understanding of mosquito breeding habitat stability in these sites in order to determine their potential for larval control.MethodsA total of 128 potential larval habitats were identified in hilltops and along the seasonal streams in the Sigalagala area of Kakamega district, western Kenya. Water availability in the habitats was followed up daily from August 3, 2006 to February 23, 2007. A habitat is defined as stable when it remains aquatic continuously for at least 12 d. Mosquito larvae were observed weekly. Frequencies of aquatic, stable and larvae positive habitats were compared between the hilltop and seasonal stream area using χ2-test. Factors affecting the presence/absence of Anopheles gambiae larvae in the highlands were determined using multiple logistic regression analysis.ResultsTopography significantly affected habitat availability and stability. The occurrence of aquatic habitats in the hilltop was more sporadic than in the stream area. The percentage of habitat occurrences that were classified as stable during the rainy season is 48.76% and 80.79% respectively for the hilltop and stream area. Corresponding frequencies of larvae positive habitats were 0% in the hilltop and 5.91% in the stream area. After the rainy season, only 23.42% of habitat occurrences were stable and 0.01% larvae positive habitats were found in the hilltops, whereas 89.75% of occurrences remained stable in the stream area resulting in a frequency of 12.21% larvae positive habitats. The logistic regression analysis confirmed the association between habitat stability and larval occurrence and indicated that habitat surface area was negatively affecting the occurrence of An. gambiae larvae. While An. gambiae and An. funestus larvae occurred throughout the study period along the streams, a total of only 15 An. gambiae larvae were counted in the hilltops, and no An. funestus were found. Moreover, no larvae managed to develop into adults in the hilltops, and the density of adult An. gambiae was consistently low, averaging at 0.06 females per house per survey.ConclusionThe occurrence of malaria vector larvae in the hilltop area was uncommon as a result of the low availability and high instability of habitats. To optimize the cost-effectiveness of malaria interventions in the western Kenya highlands, larval control should be focused primarily along the streams, as these are likely the only productive habitats at high altitude.

Effects of co-habitation between Anopheles gambiae s.s. and Culex quinquefasciatus aquatic stages on life history traits

BackgroundThe effective measures for the control of malaria and filariasis vectors can be achieved by targeting immature stages of anopheline and culicine mosquitoes in productive habitat. To design this strategy, the mechanisms (like biotic interactions with conspecifc and heterospecific larvae) regulating mosquito aquatic stages survivorship, development time and the size of emerging adults should be understood. This study explored the effect of co-habitation between An. gambiae s.s. and Cx. quinquefasciatus on different life history traits of both species under different densities and constant food supply in the habitats of the same size under semi-natural conditions.MethodsExperiments were set up with three combinations; Cx. quinquefasciatus alone (single species treatment), An. gambiae s.s. alone (single species treatment); and An. gambiae s.s. with Cx. quiquefasciatus (co-habitation treatment) in different densities in semi field situation.ResultsThe effect of co-habitation of An. gambiae s.s. and Cx. quinquefasciatus was found to principally affect three parameters. The wing-lengths (a proxy measure of body size) of An. gambiae s.s. in co-habitation treatments were significantly shorter in both females and males than in An. gambiae s.s single species treatments. In Cx. quinquefasciatus, no significant differences in wing-length were observed between the single species and co-habitation treatments. Daily survival rates were not significantly different between co-habitation and single species treatments for both An. gambiae s.s. and Cx. quinquefasciatus. Developmental time was found to be significantly different with single species treatments developing better than co-habitation treatments. Sex ratio was found to be significantly different from the proportion of 0.5 among single and co-habitation treatments species at different densities. Single species treatments had more males than females emerging while in co-habitation treatments more females emerged than males. In this study, there was no significant competitive survival advantage in co-habitation.ConclusionThese results suggest that co-habitation of An. gambiae s.s. and Cx. quinquefasciatus in semi-natural conditions affect mostly An. gambiae s.s. body size. Hence, more has to be understood on the effects of co-habitation of An. gambiae s.s. and Cx. quinquefasciatus in a natural ecology and its possible consequences in malaria and filariasis epidemiology.