Malaria “hotspots” within a larger hotspot; what’s the role of behavioural factors in fine scale heterogeneity in western Kenya?

Background: Malaria remains a major public health problem in Kenya accounting for the highest morbidity and mortality especially among children. Previous reports indicate that infectious agents display heterogeneity in both space and time and malaria is no exception. Heterogeneity has been shown to reduce the effectiveness of interventions. Previous studies have implicated genetic (both human and parasite) and environmental factors as mainly responsible for variation in malaria risk. Human behaviour and its potential risk for contributing to variation in malaria risk has not been extensively explored.Objective: To determine if there were behavioural differences between the people living in hotspots (high malaria burden) and cold spots (low malaria burden) within a geographically homogeneous and high malaria transmission region.Design: A prospective closed cohort study.Setting: The study was conducted in the Health and Demographic Surveillance Site in Bungoma East sub-County.Subjects: A total of 400 people in randomly selected households in both the fever hotspots and cold spots were tested for malaria at quarterly intervals using malaria rapid diagnostic tests (RDTs).Results: Significant heterogeneity in malaria incidence and prevalence was observed between villages. Incidence of malaria was significantly higher in the hotspots (high malaria burden areas) compared to the cold spots (low malaria burden) (49 episodes per 1000 person months compared to 26/1000, t test p < 0.001). The incidence also varied significantly among the individual villages by season (P: 0.0071). Knowledge on malaria therapy was significantly  associated with whether one was in the cold spot or hotspot (P: 0.033). Behavioural practices relating to ITN use were significantly associated with region during particular seasons (P: 0.0001 and P: 0.0001 respectively).Conclusion: There is marked and significant variation in the incidence of malaria among the villages creating actual hotspots of malaria within the larger hotspot. There is a significant difference in malaria infections between the hotspots and cold spots. Knowledge on malaria therapy and behavioural factors such as ITN use may contribute to the observed differences during some seasons

Malaria “hotspots” within a larger hotspot; what’s the role of behavioural factors in fine scale heterogeneity in western Kenya?

Background: Malaria remains a major public health problem in Kenya accounting for the highest morbidity and mortality especially among children. Previous reports indicate that infectious agents display heterogeneity in both space and time and malaria is no exception. Heterogeneity has been shown to reduce the effectiveness of interventions. Previous studies have implicated genetic (both human and parasite) and environmental factors as mainly responsible for variation in malaria risk. Human behaviour and its potential risk for contributing to variation in malaria risk has not been extensively explored.Objective: To determine if there were behavioural differences between the people living in hotspots (high malaria burden) and coldspots (low malaria burden) within a geographically homogeneous and high malaria transmission region.Design: A prospective closed cohort study.Setting: The study was conducted in the Health and Demographic Surveillance Site in Bungoma East sub-County.Subjects: A total of 400 people in randomly selected households in both the fever hotspots and cold spots were tested for malaria at quarterly intervals using malaria rapid diagnostic tests (RDTs).Results: Significant heterogeneity in malaria incidence and prevalence was observed between villages. Incidence of malaria was significantly higher in the hotspots (high malaria burden areas) compared to the coldspots (low malaria burden) (49 episodes per 1000 person months compared to 26/1000, ttest p < 0.001). The incidence also varied significantly among the individual villages by season (P: 0.0071). Knowledge on malaria therapy was significantly associated with whether one was in the cold spot or hotspot (P: 0.033). Behavioural practices relating to ITN use were significantly associated with region during particular seasons (P: 0.0001 and P: 0.0001 respectively).Conclusion: There is marked and significant variation in the incidence of malaria among the villages creating actual hotspots of malaria within the larger hotspot. There is a significant difference in malaria infections between the hotspots and cold spots. Knowledge on malaria therapy and behavioural factors such as ITN use may contribute to the observed differences during some seasons

Prevalence, heterogeneity of asymptomatic malaria infections and associated factors in a high transmission region

Background: Although current reports have shown a reduction in malaria cases, the disease still remains a major public health problem in Kenya. In most endemic regions, the majority of infections are asymptomatic which means those infected may not even know and yet they remain infectious to the mosquitoes. Asymptomatic infections are a major threat to malaria control programs since they act as silent reservoirs for the malaria parasites.Objective: The study sought to determine the prevalence of asymptomatic malaria infections, whether they show heterogeneity spatially, across age groups and across time as well as their determinants in a high transmission region.Study Design: This was part of a larger prospective cohort study on malaria indices in the HDSS.Study Setting: The study was conducted in the Webuye Health and Demographic Surveillance Site in Bungoma East Sub-County.Study Subjects: Quarterly parasitological surveys were conducted for a cohort of 400 participants from randomly selected households located in known fever “hotspots” and “coldspots”. Follow-up of all the participants continued for a period of one year. Generalized estimating equations were used to model risk factors associated with asymptomatic parasitemia.Results: Of the total 321 malaria infections detected during the five cross-sectional surveys conducted over the period of one year, almost half (46.3%) of these were asymptomatic. Overall, most of the asymptomatic cases (67%) were in households within known fever “hotspots”. The proportion of infections that were asymptomatic in the coldspots were 73.1%, 31.8%, 13.3%, 55.6% and 48.2% during the first, second, third, fourth and fifth visits respectively. In the known fever “hotspots”, the proportion of infections without symptoms was 47.7%, 48.5%, 35%, 41.3% and 47.5% during the first, second, third, fourth and fifth visits respectively. Factors associated with asymptomatic malaria include; the village one lives: people living in village M were twice likely to be asymptomatic (A.O.R: 2.141, C.I: 0.03 - 1.488), age: children aged between 6 to 15 years were more than twice likely to be asymptomatic (A.O.R: 2.67, C.I. 0.434 - 1.533) and the season: infections during the dry season (January) were less likely to be asymptomatic (A.O.R: 0.26, C.I: -2.289 - 0.400).Conclusion: The prevalence of asymptomatic infections in this region is still very high. The highest proportion of asymptomatic infections was registered in a fever coldpspot village which may explain why the village is a fever coldspot in the first place. There is a need for active surveillance to detect the asymptomatic cases as well as treat them in-order to reduce the reservoir. Targeting interventions to the asymptomatic individuals will further reduce the transmission within this region

Effects of a botanical larvicide derived from Azadirachta indica (the neem tree) on oviposition behaviour in Anopheles gambiae s.s. mosquitoes

More focus is given to mosquito larval control due to the necessity to use several control techniques together in integrated vector management programmes. Botanical products are thought to be able to provide effective, sustainable and cheap mosquito larval control tools. However, bio-larvicides like Azadirachta indica (neem) could repel adult mosquitoes from laying their eggs in the treated larval habitats. In this study the response of Anopheles gambiae s.s. mosquitoes towards varying doses of crude aqueous neem extracts was examined. Non-choice oviposition tests were used to measure the proportion of mosquitoes laying on the first or second night, or not laying at all, when compared to the control. For each individual mosquito, the number of eggs laid and/or retained in the ovary was counted to determine the relationship between wing length and egg production. Larger female mosquitoes produced larger egg batches. The results show that at a dose of 0.1 g/l, a concentration previously found to be effective at controlling mosquito larvae, the oviposition behaviour of adult female mosquitoes was not significantly affected. The results indicate that the mosquitoes would expose progeny to this neem control tool, making the use of these simple neem wood extracts effective and potentially sustainable

Longevity of Genotype-Specific Immune Responses to Plasmodium falciparum Merozoite Surface Protein 1 in Kenyan Children from Regions of Different Malaria Transmission Intensity

Naturally acquired immunity to Plasmodium falciparum presents a changing landscape as malaria control programs and vaccine initiatives are implemented. Determining which immunologic indicators remain surrogates of past infection, as opposed to mediators of protection, led us to compare stability of immune responses across regions with divergent malaria transmission intensities. A repeat cross-sectional study of Kenyan children from a malaria-holoendemic area and an epidemic-prone area was used to examine longitudinal antibody and interferon-gamma (IFN-gamma) responses to the 3D7 and FVO variants of merozoite surface protein 1 (MSP1). Antibodies to MSP1 were common in both study populations and did not significantly wane over a 21-month time period. IFN-gamma responses were less frequent and rapidly disappeared in children after a prolonged period of no malaria transmission. Antibody and IFN-gamma responses rarely correlated with each other; however, MSP1-specific IFN-gamma response correlated with lack of concurrent P. falciparum parasitemia of the same genotype, though only statistically significantly in the malaria-holoendemic region (odds ratio = 0.31, 95% confidence interval = 0.12-0.84). This study affirms that antimalarial antibodies are informative for evaluation of history of malaria exposure within individuals, whereas cell-mediated immunity, though short lived under natural exposure conditions, might provide an assessment of recent infection and protection from parasitemia

Evaluation of Polyethylene-Based Long Lasting Treated Bed Net Netprotect on Anopheles

We studied the effect on malaria incidence, mosquito abundance, net efficacy, net use rate, chemical analysis, and holes of a long lasting insecticide treated bed net (Netprotect) in western Kenya, 2007–2010. Nets were hung in 150 households 6 months before they were hung in a second, 2 km away. Indoor resting densities were monitored by pyrethrum spray catch and malaria cases by passive detection using clinical manifestations and rapid diagnostic test. The probability of finding An. arabiensis in the control area was 2.6 times higher than that in intervention area during the first 6 months. Human blood feeding index of Anopheles funestus declined 17%. After bed nets were hung in the second area, malaria incidence declined 25% down to the level in the first area. Incidence remained at this low level for 2 years. 90% of collected nets were efficacious after 3-year use. Deltamethrin dosage declined from 1.9 to 0.5 g/kg over 3 years. Attrition rate after 3 years was 21%. WHO hole index changed from 333 to 114 to 381 over the three years. This index summarizes the numbers of holes in size categories and multiplies with the mean hole area per category. It is very sensitive to the impact of big holes in a few nets

Status of insecticide susceptibility in Anopheles arabiensis from Mwea rice irrigation scheme, Central Kenya

BACKGROUND: Control of the Anopheline mosquito vectors of malaria by use of insecticides has been shown to impact on both morbidity and mortality due to this disease. Evidence of insecticide resistance in different settings necessitates surveillance studies to allow prompt detection of resistance should it arise and thus enable its management. Possible resistance by Anopheles arabiensis mosquitoes from Mwea rice irrigation scheme in Central Kenya to insecticides in the four classes of insecticides approved by WHO for indoor residual spraying was investigated. METHODS: Susceptibility to DDT (an organochlorine), fenitrothion (an organophosphate), bendiocarb (a carbamate), lambdacyhalothrin and permethrin (both pyrethroids) was tested using standard WHO diagnostic bioassay kits. Bioassays were performed on non-blood fed mosquitoes one- to three-day old. Knockdown was recorded every 10 min and mortality 24 h post-exposure was noted. RESULTS: Mortality 24 h post-exposure was 100% for all insecticides except for lambdacyhalothrin, which averaged 99.46%. Knockdown rates at 10 min intervals were not significantly different between the Mwea population and the susceptible KISUMU strain of Anopheles gambiae sensu stricto control. The KDT(50 )and KDT(95 )values for the Mwea population were either lower than those for the control or higher by factors of no more than 2 for most comparisons and compared well with those of An. gambiae sensu lato categorized as susceptible in other studies. CONCLUSION: These results suggest that the Mwea population of An. arabiensis is susceptible to all the insecticides tested. This implies that vector control measures employing any of these insecticides would not be hampered by resistance

Intermittent Preventive Treatment in Infants for the Prevention of Malaria in Rural Western Kenya: A Randomized, Double-Blind Placebo-Controlled Trial

Background Intermittent preventive treatment in infants (IPTi) with sulphadoxine-pyrimethamine (SP) for the prevention of malaria has shown promising results in six trials. However, resistance to SP is rising and alternative drug combinations need to be evaluated to better understand the role of treatment versus prophylactic effects. Methods Between March 2004 and March 2008, in an area of western Kenya with year round malaria transmission with high seasonal intensity and high usage of insecticide-treated nets, we conducted a randomized, double-blind placebo-controlled trial with SP plus 3 days of artesunate (SP-AS3), 3 days of amodiaquine-artesunate (AQ3-AS3), or 3 days of short-acting chlorproguanil-dapsone (CD3) administered at routine expanded programme of immunization visits (10 weeks, 14 weeks and 9 months). Principal Findings 1,365 subjects were included in the analysis. The incidence of first or only episode of clinical malaria during the first year of life (primary endpoint) was 0.98 episodes/person-year in the placebo group, 0.74 in the SP-AS3 group, 0.76 in the AQ3-AS3 group, and 0.82 in the CD3 group. The protective efficacy (PE) and 95% confidence intervals against the primary endpoint were: 25.7% (6.3, 41.1); 25.9% (6.8, 41.0); and 16.3% (−5.2, 33.5) in the SP-AS3, AQ3-AS3, and CD3 groups, respectively. The PEs for moderate-to-severe anaemia were: 27.5% (−6.9, 50.8); 23.1% (−11.9, 47.2); and 11.4% (−28.6, 39.0). The duration of the protective effect remained significant for up to 5 to 8 weeks for SP-AS3 and AQ3-AS3. There was no evidence for a sustained beneficial or rebound effect in the second year of life. All regimens were well tolerated. Conclusions These results support the view that IPTi with long-acting regimens provide protection against clinical malaria for up to 8 weeks even in the presence of high ITN coverage, and that the prophylactic rather than the treatment effect of IPTi appears central to its protective efficacy

Sporadic paediatric diarrhoeal illness in urban and rural sites in Nyanza province, Kenya

Objective: Investigate differences in the infectious aetiology, health seeking behaviour, and provider practices with regard to diarrhoeal illness among children presenting to urban versus rural clinics in Western Kenya.Design: Laboratory-based, passive surveillance.Setting: The urban portion of the study was conducted at the paediatric outpatient clinic of Nyanza Provincial Hospital in Kisumu. The rural portion of the study was conducted at four outpatient clinics in the Asembo Bay community approximately 20 kilometers west of Kisumu.Subjects: Children aged less than five years presenting to medical facilities for the treatment of diarrhoea from October 2001-October 2003 at the urban site and May 1997-April 2003 for the rural sites.Results: Among the 1303 urban and 1247 rural specimens collected, 24% of specimens yielded a bacterial pathogen (24% urban, 25% rural). Campylobacter was the predominant bacterial pathogen (17% urban, 15% rural), followed by Shigella and nontyphoidal Salmonella (both 4% urban and 5% rural). In both communities, susceptibilities of these pathogens to the most commonly prescribed antibiotics was low

Broadly reactive antibodies specific for Plasmodium falciparum MSP-119 are associated with the protection of naturally exposed children against infection

BACKGROUND: The 19 kDa C-terminal region of Plasmodium falciparum Merozoite Surface Protein-1 is a known target of naturally acquired humoral immunity and a malaria vaccine candidate. MSP- 119 has four predominant haplotypes resulting in amino acid changes labelled EKNG, QKNG, QTSR and ETSR. IgG antibodies directed against all four variants have been detected, but it is not known if these variant specific antibodies are associated with haplotype-specific protection from infection. METHODS: Blood samples from 201 healthy Kenyan adults and children who participated in a 12-week treatment time-to-infection study were evaluated. Venous blood drawn at baseline (week 0) was examined for functional and serologic antibodies to MSP-119 and MSP-142 variants. MSP-119 haplotypes were detected by a multiplex PCR assay at baseline and weekly throughout the study. Generalized linear models controlling for age, baseline MSP-119 haplotype and parasite density were used to determine the relationship between infecting P. falciparum MSP-119 haplotype and variant-specific antibodies. RESULTS: A total of 964 infections resulting in 1,533 MSP-119 haplotypes detected were examined. The most common haplotypes were EKNG and QKNG, followed by ETSR and QTSR. Children had higher parasite densities, greater complexity of infection (\u3e1 haplotype), and more frequent changes in haplotypes over time compared to adults. Infecting MSP-119 haplotype at baseline (week 0) had no influence on haplotypes detected over the subsequent 11 weeks among children or adults. Children but not adults with MSP-119 and some MSP-142 variant antibodies detected by serology at baseline had delayed time-to-infection. There was no significant association of variant-specific serology or functional antibodies at baseline with infecting haplotype at baseline or during 11 weeks of follow up among children or adults. CONCLUSIONS: Variant transcending IgG antibodies to MSP-119 are associated with protection from infection in children, but not adults. These data suggest that inclusion of more than one MSP-119 variant may not be required in a malaria blood stage vaccine