[Show abstract][Hide abstract] ABSTRACT: Background:
The extensive use of pyrethroids for control of malaria vectors, driven by their cost, efficacy and safety, has led to widespread resistance. To favor their sustainable use, the World Health Organization (WHO) formulated an insecticide resistance management plan, which includes the identification of the mechanisms of resistance and resistance surveillance. Recognized physiological mechanisms of resistance include target site mutations in the para voltage-gated sodium channel, metabolic detoxification and penetration resistance. Such understanding of resistance mechanisms has allowed the development of resistance monitoring tools, including genotyping of the kdr mutation L1014F/S in the para gene.
The sequence-based technique RNA-seq was applied to study changes in the transcriptome of deltamethrin-resistant and -susceptible Anopheles gambiae mosquitoes from the Western Province of Kenya. The resulting gene expression profiles were compared to data in the most recent literature to derive a list of candidate resistance genes. RNA-seq data were analyzed also to identify sequence polymorphisms linked to resistance.
A total of five candidate-resistance genes (AGAP04177, AGAP004572, AGAP008840, AGAP007530 and AGAP013036) were identified with altered expression between resistant and susceptible mosquitoes from West and East Africa. A change from G to C at position 36043997 of chromosome 3R resulting in A101G of the sulfotransferase gene AGAP009551 was significantly associated with the resistance phenotype (odds ratio: 5.10). The kdr L1014S mutation was detected at similar frequencies in both phenotypically resistant and susceptible mosquitoes, suggesting it is no longer fully predictive of the resistant phenotype.
Overall, these results support the conclusion that resistance to pyrethroids is a complex and evolving phenotype, dependent on multiple gene functions including, but not limited to, metabolic detoxification. Functional convergence among metabolic detoxification genes may exist, with the role of each gene being modulated by the life history and selection pressure on mosquito populations. As a consequence, biochemical assays that quantify overall enzyme activity may be a more suitable method for predicting metabolic resistance than gene-based assays.
[Show abstract][Hide abstract] ABSTRACT: Asymptomatic malaria infections represent a major challenge in malaria control and elimination in Africa. They are reservoirs of malaria parasite that can contribute to disease transmission. Therefore, identification and control of asymptomatic infections are important to make malaria elimination feasible. In this study, we investigated the extent and distribution of asymptomatic malaria in Western Kenya and examined how varying parasitemia affects performance of diagnostic methods including microscopy, conventional PCR, and quantitative PCR. In addition, we compared parasite prevalence rates and parasitemia levels with respect to topography and age in order to explore factors that influence malaria infection. Over 11,000 asymptomatic blood samples from children and adolescents up to 18 years old representing broad areas of Western Kenya were included. Quantitative PCR revealed the highest parasite positive rate among all methods and malaria prevalence in western Kenya varied widely from less than 1% to over 50%. A significantly lower parasitemia was detected in highland than in lowland samples and this contrast was also observed primarily among submicroscopic samples. Although we found no correlation between parasitemia level and age, individuals of younger age group (aged <14) showed significantly higher parasite prevalence. In the lowlands, individuals of aged 5-14 showed significantly higher prevalence than those under age 5. Our findings highlight the need for a more sensitive and time-efficient assay for asymptomatic malaria detection particularly in areas of low-transmission. Combining QPCR with microscopy can enhance the capacity of detecting submicroscopic asymptomatic malaria infections.
[Show abstract][Hide abstract] ABSTRACT: Background
Epidemiological characteristics of clinical malaria may differ from asymptomatic infections, thus both cross-sectional parasite screening and longitudinal clinical case surveillance are necessary for malaria transmission monitoring and control.Methods
In order to monitor malaria transmission, surveillance of clinical malaria from two years of active case surveillance in three cohorts of 6,750 individuals, asymptomatic parasitaemia cases of 5,300 individuals and clinical cases in three study areas were carried out in the western Kenyan highlands in 2009 and 2010. Age distribution, seasonality and spatial clustering were analysed.ResultsThe results revealed a significant difference in the age distribution of clinical cases between passive and active case surveillance, and between clinical case rate and asymptomatic parasite rate. The number of reported cases from health facilities significantly underestimated clinical malaria incidence. The increase in asymptomatic parasite prevalence from low to high transmission seasons was significantly higher for infants (<two years) and adults (¿15 years) (500% increase) than that for children (two to 14 years, 65%), but the increase in clinical incidence rates was significantly higher for children (700%) than that for adults (300%). Hotspot of asymptomatic infections remained unchanged over time, whereas new clusters of clinical malaria cases emerged in the uphill areas during the peak season.Conclusions
Different surveillance methods revealed different characteristics of malaria infections. The new transmission hotspots identified during the peak season with only active case surveillance is an important observation with clear implications in the context of malaria elimination. Both mass parasite screening and active case surveillance are essential for malaria transmission monitoring and control.
[Show abstract][Hide abstract] ABSTRACT: Background
Models for malaria transmission are usually compared based on the quantities tracked, the form taken by each term in the equations, and the qualitative properties of the systems at equilibrium. Here five models are compared in detail in order to develop a set of performance measures that further illuminate the differences among models.
Five models of malaria transmission are compared. Parameters are adjusted to correspond to similar biological quantities across models. Nine choices of parameter sets/initial conditions are tested for all five models. The relationship between malaria incidence in humans and (1) malaria incidence in vectors, (2) man-biting rate, and (3) entomological inoculation rate (EIR) at equilibrium is tested for all models. A sensitivity analysis for all models is conducted at all parameter sets. Overall sensitivities are ranked for each of the five models. A set of simple control interventions is tested on two of the models.
Four of these models behave consistently over a set of nine choices of parameters and initial conditions, with one behaving significantly differently. Two of the models do not match reported entomological inoculation rate data well. The sensitivity profiles, although consistently having similar top parameters, vary not only between models but among choices of parameters and initial conditions. A numerical experiment on two of the models illustrates the effect of these differences on control strategies, showing significant differences between models in predicting which of the control measures are more effective.
A set of benchmark tests based on performance measures are developed to be used on any proposed malaria transmission model to test its overall behaviour in comparison to both other models and data sets.
[Show abstract][Hide abstract] ABSTRACT: Background & objectives:
Malaria is the major cause of morbidity and mortality in sub-Saharan Africa. A child below five years dies after every 30 min. Highland areas under land use change impact on malaria transmission by altering the microclimate of the immature stages and adult mosquitoes. Adult vector population dynamics is important because it is an indicator of transmission risk of the disease. This study was to investigate the effects of microclimatic changes on the mosquito indoor-resting behavior.
The study was conducted at a highland site of Marani and at a lowland site of Kombewa where 30 houses were randomly selected at either site. Outdoor and indoor weather conditions were monitored throughout the study period. Indoor mosquitoes were collected using the pyrethrum spray catch method, gonotrophic stage of the females determined and species identified to species level using rDNA polymerase chain reaction method. ELISA was carried out to determine the Plasmodium sporozoites in mosquitoes.
Anopheles gambiae s.s. was more abundant at the highland site whereas An. funestus at the lowland site. Indoor densities were highest in June 2003 at both the sites: An. gambiae at the highland site and An. funestus at the lowland site. There was an association between An. gambiae s.s. abundance and relative humidity at the highland site. Combined entomological inoculation rate (EIR) for both the vector species was 0.4 infected bite per year (ib/yr) at the highland site and 31.1 ib/yr at the lowland site. Prolonged indoor spraying with insecticide decreased vector indoor abundance.
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: The main objective was to investigate malaria transmission dynamics in three different sites, two highland villages (Fort Ternan and Lunyerere) and a lowland peri-urban area (Nyalenda) of Kisumu city. Adult mosquitoes were collected using PSC and CDC light trap while malaria parasite incidence data was collected from a cohort of children on monthly basis. Rainfall, humidity and temperature data were collected by automated weather stations. Negative binomial and Poisson generalized additive models were used to examine the risk of being infected, as well as the association with the weather variables. Anopheles gambiae s.s. was most abundant in Lunyerere, An. arabiensis in Nyalenda and An. funestus in Fort Ternan. The CDC light traps caught a higher proportion of mosquitoes (52.3%) than PSC (47.7%), although not significantly different (P = 0.689). The EIR's were 0, 61.79 and 6.91 bites/person/year for Fort Ternan, Lunyerere and Nyalenda. Site, month and core body temperature were all associated with the risk of having malaria parasites (P < 0.0001). Rainfall was found to be significantly associated with the occurrence of P. falciparum malaria parasites, but not relative humidity and air temperature. The presence of malaria parasite-infected children in all the study sites provides evidence of local malaria transmission.
Full-text · Article · Sep 2012 · Journal of Tropical Medicine
[Show abstract][Hide abstract] ABSTRACT: Malaria resurgence in highland regions of East Africa has been on increase. The spatio-temporal distribution of larval habitats of malaria vectors determines the distribution of adult vectors, hence, disease transmission. Vector's ecology is necessary for strategic vector control through effective plan for source reduction. Mapping of the larval habitats is necessary for targeted control measures. The purpose of this study is to assess and compare the spatial and seasonal variations in anopheline larval habitats in Western Kenya.
A comparative study was conducted on spatial distribution of GPS geo-located anopheline larval habitats in relation to highland and lowland environments. Land use types were categorized and all potential aquatic habitats of malaria vectors were examined in February, May, August and November 2004. Data analyses were performed using SAS JMP software.
Results showed a higher percentage of Anopheles gambiae s.s. (70.9%) than An. funestus (29.1%) in highland. In the lowland, An. gambiae s.l. comprised 60.1% while An. funestus represented 39.9%. The distribution of larval breeding is confined to the valley bottom in the highland while it was dispersed in the lowland. Land use type influenced the occurrence of positive breeding habitats in the highland. In the lowland, distribution was due to seasonality. We found high proportion of potential and positive breeding sites in cultivated swamps and farmlands at the highland site. These results suggest that swamp cultivation increases the availability and suitability of larval breeding habitats of malaria vectors, thus malaria transmission in the Western Kenya highlands environment.
Full-text · Article · Jun 2012 · Journal of vector borne diseases
[Show abstract][Hide abstract] ABSTRACT: Assessment of malaria endemicity at different altitudes and transmission intensities, in the era of dwindling vector densities in the highlands, will provide valuable information for malaria control and surveillance. Measurement of serum anti-malarial antibodies is a useful marker of malaria exposure that indicates long-term transmission potential. We studied the serologic evidence of malaria endemicity at two highland sites along a transmission intensity cline. An improved understanding of the micro-geographic variation in malaria exposure in the highland ecosystems will be relevant in planning effective malaria control.
Total IgG levels to Plasmodium falciparum MSP-119 were measured in an age-stratified cohort (< 5, 5-14 and ≥ 15 years) in 795 participants from an uphill and valley bottom residents during low and high malaria transmission seasons. Antibody prevalence and level was compared between different localities. Regression analysis was performed to examine the association between antibody prevalence and parasite prevalence. Age-specific MSP-119 seroprevalence data was fitted to a simple reversible catalytic model to investigate the relationship between parasite exposure and age.
Higher MSP-119 seroprevalence and density were observed in the valley residents than in the uphill dwellers. Adults (> 15 years) recorded high and stable immune response in spite of changing seasons. Lower responses were observed in children (≤ 15 years), which, fluctuated with changing seasons particularly in the valley residents. In the uphill population, annual seroconversion rate (SCR) was 8.3% and reversion rate was 3.0%, with seroprevalence reaching a plateau of 73.3% by age of 20. Contrary, in the valley bottom population, the annual SCR was 35.8% and the annual seroreversion rate was 3.5%, and seroprevalence in the population had reached 91.2% by age 10.
The study reveals the micro-geographic variation in malaria endemicity in the highland eco-system; this validates the usefulness of sero-epidemiological tools in assessing malaria endemicity in the era of decreasing sensitivity of conventional tools.
Full-text · Article · Mar 2012 · BMC Infectious Diseases
[Show abstract][Hide abstract] ABSTRACT: Following severe malaria epidemics in the western Kenya highlands after the late 1980s it became imperative to undertake eco-epidemiological assessments of the disease and determine its drivers, spatial-temporal distribution and control strategies. Extensive research has indicated that the major biophysical drivers of the disease are climate change and variability, terrain, topography, hydrology and immunity. Vector distribution is focalized at valley bottoms and abundance is closely related with drainage efficiency, habitat availability, stability and productivity of the ecosystems. Early epidemic prediction models have been developed and they can be used to assess climate risks that warrant extra interventions with a lead time of 2-4 months. Targeted integrated vector management strategies can significantly reduce the cost on the indoor residual spraying by targeting the foci of transmission in transmission hotspots. Malaria control in the highlands has reduced vector population by 90%, infections by 50-90% in humans and in some cases transmission has been interrupted. Insecticide resistance is increasing and as transmission decreases so will immunity. Active surveillance will be required to monitor and contain emerging threats. More studies on eco-stratification of the disease, based on its major drivers, are required so that interventions are tailored for specific ecosystems. New and innovative control interventions such as house modification with a one-application strategy may reduce the threat from insecticide resistance and low compliance associated with the use of ITNs.
[Show abstract][Hide abstract] ABSTRACT: A large proportion of mosquito larval habitats in urban and rural communities in sub-Saharan Africa are man-made. Therefore, community-based larval source management (LSM) could make a significant contribution to malaria control in an integrated vector management approach. Here we implemented an exploratory study to assess malaria prevalence and people's knowledge, attitudes and practices on malaria transmission, its control and the importance of man-made aquatic habitats for the development of disease vectors in one peri-urban lowland and two rural highland communities in western Kenya. We implemented monthly cross-sectional malaria surveys and administered a semi-structured questionnaire in 90 households, i.e. 30 households in each locality. Malaria prevalence was moderate (3.2-6.5%) in all sites. Nevertheless, residents perceived malaria as their major health risk. Thirty-two percent (29/90) of all respondents did not know that mosquitoes are responsible for the transmission of malaria. Over two-thirds (69/90) of the respondents said that mosquito breeding site could be found close to their homes but correct knowledge of habitat characteristics was poor. Over one-third (26/67) believed that immature mosquitoes develop in vegetation. Man-made pools, drainage channels and burrow pits were rarely mentioned. After explaining where mosquito larvae develop, 56% (50/90) felt that these sites were important for their livelihood. Peri-urban residents knew more about mosquitoes' role in malaria transmission, could more frequently describe the larval stages and their breeding habitats, and were more likely to use bed nets even though malaria prevalence was only half of what was found in the rural highland sites (p<0.05). This was independent of their education level or socio-economic status. Hence rural communities are more vulnerable to malaria infection, thus calling for additional methods to complement personal protection measures for vector control. Larval source management was the most frequently mentioned (30%) tool for malaria control but was only practiced by 2 out of 90 respondents. Targeting the larval stages of malaria vectors is an underutilized malaria prevention measure. Sustainable elimination or rendering of such habitats unsuitable for larval development needs horizontally organized, community-based programs that take people's needs into account. Innovative, community-based training programs need to be developed to increase people's awareness of man-made vector breeding sites and acceptable control methods need to be designed in collaboration with the communities.
[Show abstract][Hide abstract] ABSTRACT: Spatial and temporal variations in the distribution of anopheline larval habitats and land use and land cover (LULC) changes can influence malaria transmission intensity. This information is important for understanding the environmental determinants of malaria transmission heterogeneity, and it is critical to the study of the effects of environmental changes on malaria transmission. In this study, we investigated the spatial and temporal variations in the distribution of anopheline larval habitats and LULC changes in western Kenya highlands over a 4-year period. Anopheles gambiae complex larvae were mainly confined to valley bottoms during both the dry and wet seasons. Although An. gambiae larvae were located in man-made habitats where riparian forests and natural swamps had been cleared, Anopheles funestus larvae were mainly found in permanent habitats in pastures. The association between land cover type and occurrence of anopheline larvae was statistically significant. The distribution of anopheline positive habitats varied significantly between months, during the survey. In 2004, the mean density of An. gambiae was significantly higher during the month of May, whereas the density of An. funestus peaked significantly in February. Over the study period, major LULC changes occurred mostly in the valley bottoms. Overall, farmland increased by 3.9%, whereas both pastures and natural swamps decreased by 8.9% and 20.9%, respectively. The area under forest cover was decreased by 5.8%. Land-use changes in the study area are favorable to An. gambiae larval development, thereby risking a more widespread distribution of malaria vector habitats and potentially increasing malaria transmission in western Kenya highlands.
Full-text · Article · Dec 2009 · The American journal of tropical medicine and hygiene
[Show abstract][Hide abstract] ABSTRACT: To assess the contributions of both microbial larvicides and insecticide-treated nets (ITNs) in terms of reducing malaria incidence in an integrated vector management programme in an area moderately endemic for malaria in the western Kenyan highlands.
A pre-post, control group design was used. Larval and adult vector populations were surveyed weekly in six separate valley communities. The incidence of Plasmodium infections in children 6 months to 13 years of age was measured during the long and short rainy seasons each year. Baseline data were collected for 17 months, after which Bacillus-based larvicides were applied weekly to aquatic habitats in three of the valleys for another 19 months. At around the same time the larviciding was initiated, ITNs were introduced gradually into all study communities by the National Malaria Control Programme. The effect of larviciding, ITNs and other determinants of malaria risk was assessed by means of generalized estimating equations.
The risk of acquiring new parasite infections in children was substantially and independently reduced by ITN use (odds ratio, OR: 0.69; 95% confidence interval, CI: 0.48-0.99) and larvicide application (OR: 0.44; 95% CI: 0.23-0.82), after adjusting for confounders.
Vector control with microbial larvicides enhanced the malaria control achieved with ITNs alone. Anti-larval measures are a promising complement to ITN distribution in the economically important highland areas and similar transmission settings in Africa.
Full-text · Article · Sep 2009 · Bulletin of the World Health Organisation
[Show abstract][Hide abstract] ABSTRACT: Simple modifications of typical rural house design can be an effective and relatively inexpensive method of reducing indoor mosquito vector densities and consequently decreasing malaria transmission. Public health scientists have shown the potential for house design to protect people against malaria, yet this type of intervention remains virtually ignored. A randomized-controlled study was, therefore, undertaken to determine the effects of this method of vector control on the density of indoor resting malaria vectors in a rice irrigation scheme area in lowlands of western Kenya.
Ten treatment houses were modified with ceilings of papyrus mats and insecticide-treated netting (ITN) and tested against ten control houses without papyrus ceilings. To determine densities of mosquitoes resting in homes, the pyrethrum spray method was used to simultaneously collect indoor resting malaria vectors in intervention and control houses. Each house was sampled a total of eight times over a period of four months, resulting in a total of 80 sampling efforts for each treatment. Community response to such intervention was investigated by discussions with residents.
Papyrus mats ceiling modification reduced house entry by Anopheles gambiae s.l and Anopheles funestus densities by between 78-80% and 86% respectively compared to unmodified houses. Geometric mean density of Anopheles gambiae s.l. and Anopheles funestus in modified houses were significantly lower (t(18) = 7.174, P < 0.0001 and t(18) = 2.52, P = 0.02, respectively) compared to controls. Unmodified houses were associated with relatively higher densities of malaria vectors. There was a 84% (OR 0.16, 95% CI 0.07-0.39, P < 0.0001) and 87% (OR 0.13, 95% CI 0.03-0.5, P = 0.0004) reduction in the odds of Anopheles gambiae s.l. and Anopheles funestus presence in modified houses, respectively, compared with unmodified houses. Residents responded favourably to this mode of vector control.
House modifications involving insect screen ceilings made from locally available materials and small ITN incorporated in house construction have the potential to reduce human exposure to malaria vectors, and thus parasite infection, in a rice irrigation scheme area of western Kenya. Ceiling modification is likely to be acceptable and is expected to be of greatest benefit when used in combination with other malaria control strategies.
[Show abstract][Hide abstract] ABSTRACT: Endemic malaria in most of the hot and humid African climates is the leading cause of morbidity and mortality. In the last
twenty or so years the incidence of malaria has been aggravated by the resurgence of highland malaria epidemics which hitherto
had been rare. A close association between malaria epidemics and climate variability has been reported but not universally
accepted. Similarly, the relationship between climate variability, intensity of disease mortality and morbidity coupled with
socio-economic factors has been mooted. Analyses of past climate (temperature and precipitation), hydrological and health
data (1961–2001), and socio-economics status of communities from the East African highlands confirm the link between climate
variability and the incidence and severity of malaria epidemics. The communities in the highlands that have had less exposure
to malaria are more vulnerable than their counterparts in the lowlands due to lack of clinical immunity. However, the vulnerability
of human health to climate variability is influenced by the coping and adaptive capacities of an individual or community.
Surveys conducted among three communities in the East African highlands reveal that the interplay of poverty and other socio-economic
variables have intensified the vulnerability of these communities to the impacts of malaria.
[Show abstract][Hide abstract] ABSTRACT: Water temperature is an important determinant in many aquatic biological processes, including the growth and development of malaria mosquito (Anopheles arabiensis and A. gambiae) immatures. Water turbidity affects water temperature, as suspended particles in a water column absorb and scatter sunlight and hence determine the extinction of solar radiation. To get a better understanding of the relationship between water turbidity and water temperature, a series of semi-natural larval habitats (diameter 0.32 m, water depth 0.16 m) with increasing water turbidity was created. Here we show that at midday (1300 hours) the upper water layer (thickness of 10 mm) of the water pool with the highest turbidity was on average 2.8 degrees C warmer than the same layer of the clearest water pool. Suspended soil particles increase the water temperature and furthermore change the temperature dynamics of small water collections during daytime, exposing malaria mosquito larvae, which live in the top water layer, longer to higher temperatures.
Full-text · Article · Nov 2008 · International Journal of Biometeorology
[Show abstract][Hide abstract] ABSTRACT: 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.
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).
We 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.
These 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.