Biomedical subjects

John M Vulule

Publications and source records attributed to John M Vulule.

At least 19 recordsLinked to original sources

PubMed2006

Evaluating genetic differentiation of Anopheles arabiensis in relation to larval habitats in Kenya.

Anopheles arabiensis, an important vector of malaria in sub-Saharan Africa shows great versatility in utilizing a broad range of larval habitats. Most studies on the population genetic structure of this species have focused on adult mosquitoes collected mainly indoors and have found populations within relatively short distances to be panmictic. Various authors suggested that the incipient speciation between the chromosomal forms of Anopheles gambiae s.s. in West Africa involved adaptation to different habitats of larvae. To investigate if similar process occurs in An. arabiensis, we analyzed samples from four different larval habitats alongside a sample of adult mosquitoes collected indoors at eight microsatellite loci. We tested the hypothesis that An. arabiensis is subdivided into populations that are adapted to exploit different larval habitats. Overall, the level of genetic differentiation among the larval subpopulations was low with the mean pairwise Fst estimate based on information from all the loci being 0.0232 (P=0.1691) although differentiation was only significant for comparisons between certain larval samples and the adult samples. In addition, there was strong evidence against subdivision among larvae when multilocus simultaneous assignment tests were used. These results do not provide sufficient support for the hypothesis that An. arabiensis is subdivided into subpopulations that specialize to exploit different larval habitats.

Animals↗

PubMed2006

Amodiaquine combined with sulfadoxine/pyrimethamine versus artemisinin-based combinations for the treatment of uncomplicated falciparum malaria in Africa: a meta-analysis.

Drug resistance in Plasmodium falciparum is a major obstacle to malaria control. Artemisinin-based combination therapy (ACT) is being advocated to improve treatment efficacy and to delay development of resistance. Here we summarise the available data on the efficacy of amodiaquine plus sulfadoxine/pyrimethamine (AQ+SP) versus ACTs in the treatment of uncomplicated malaria in sub-Saharan Africa. We searched for randomised trials in which patients with uncomplicated malaria treated with AQ+SP were compared with those treated with either amodiaquine plus artesunate (AQ+AS), artesunate plus sulfadoxine/pyrimethamine (AS+SP) or artemether/lumefantrine (AL). Medline, EMBASE, Cochrane Central Register of Controlled Trials and reference lists up to July 2005 were searched. Two reviewers independently extracted the data. The primary outcome measure was treatment failure by Day 28. Outcome measures were combined using a random effects model. Seven randomised trials of 4472 children were included. Trial quality was generally high. Treatment failure of AQ+SP was significantly reduced compared with AS+SP (relative risk (RR)=0.56, 95% CI 0.42-0.75), but increased compared with AL (RR=2.80, 95% CI 2.32-3.39). The overall failure rate of AQ+SP was similar compared with AQ+AS (RR=1.12, 95% CI 0.81-1.54), but there was significant heterogeneity of results across the studies. All the treatment regimens were safe and well tolerated. AQ+SP should be considered in some settings before the full implementation of an ACT.

Africa↗

PubMed2006

Use of insecticide-treated clothes for personal protection against malaria: a community trial.

BACKGROUND: The study sought to determine the effect of using insecticide-treated clothes (ITCs) on personal protection against malaria infection. The specific objectives were to determine the effect of using ITCs on the rate of infection with malaria parasites and the effect on indoor mosquito density. METHODS: This study was done in Dadaab refugee camps, North Eastern Province Kenya between April and August 2002, and involved a total of 198 participants, all refugees of Somali origin. The participants were selected through multi-stage cluster sampling. Half of the participants (treatment group) had their personal clothes worn on a daily basis (Diras, Saris, Jalbaabs, Ma'awis and shirts) and their bedding (sheets and blankets) treated with insecticide (permethrin). The other half (comparison group) had their clothes treated with placebo (plain water). Indoor mosquito density was determined from twelve households belonging to the participants; six in the treatment block and six in the comparison block. During pre-test and post-test, laboratory analysis of blood samples was done, indoor mosquito density determined and questionnaires administered. Using STATA statistical package, tests for significant difference between the two groups were conducted. RESULTS: Use of ITCs reduced both malaria infection rates and indoor mosquito density significantly. The odds of malaria infection in the intervention group were reduced by about 70 percent. The idea of using ITCs for malaria infection control was easily accepted among the refugees and they considered it beneficial. No side effects related to use of the ITCs were observed from the participants. CONCLUSION: The use of ITCs reduces malaria infection rate and has potential as an appropriate method of malaria control. It is recommended, therefore, that this strategy be considered for use among poor communities like slum dwellers and other underprivileged communities, such as street children and refugees, especially during an influx to malaria-prone regions. Further research on cost-effectiveness and sustainability of this strategy is worthwhile.

Adolescent↗

PubMed2006

Surveillance for bacterial diarrhea and antimicrobial resistance in rural western Kenya, 1997-2003.

BACKGROUND: Diarrhea is a major cause of preventable illness in sub-Saharan Africa. Although most cases of bacterial gastroenteritis do not require antimicrobial treatment, antimicrobial use is widespread. We examined the bacterial causes of diarrhea and monitored antimicrobial susceptibilities of isolates through clinic-based surveillance in a rural Kenyan community. METHODS: From May 1997 through April 2003, diarrheal stool samples from persons presenting to 4 sentinel health centers were cultured by standard techniques for routine bacterial enteric pathogens, for which antimicrobial susceptibilities were determined. A random subset of specimens was also evaluated for diarrheagenic Escherichia coli. RESULTS: Among stool specimens from 3445 persons, 1092 (32%) yielded at least 1 bacterial pathogen. Shigella species was most commonly isolated (responsible for 16% of all illnesses; 54% of isolates were Shigella flexneri). Campylobacter species and diarrheagenic E. coli predominated among children aged <5 years and were progressively replaced by Shigella species with increasing age. With the exception of Campylobacter species, susceptibility to the antimicrobials used most widely in the community was low: <40% for all isolates tested and <25% for Shigella species. Most persons were treated with an antimicrobial to which their isolate was resistant. Susceptibility to specific antimicrobials was inversely proportional to the frequency with which they were prescribed. CONCLUSIONS: The utility of available antimicrobials for treating bacterial diarrhea in rural western Kenya is substantially limited by reduced susceptibility. More judicious use of appropriate antimicrobials is warranted. Efforts to prevent illness through provision of clean water, improved hygiene, and vaccine development should be strengthened.

Drug Resistance, Multiple, Bacterial↗

PubMed2006

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 KDT50 and KDT95 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.

Agriculture↗

PubMed2006

Increased severe anemia in HIV-1-exposed and HIV-1-positive infants and children during acute malaria.

OBJECTIVE: Since the primary hematological complication in both pediatric HIV-1 and malaria is anemia, co-infection with these pathogens may promote life-threatening severe malarial anemia (SMA). The primary objective of the study was to determine if HIV-1 exposure [HIV-1(exp)] and/or HIV-1 infection [HIV-1(+)] increased the prevalence of SMA in children with acute malaria. DESIGN: The effect of HIV-1 exposure and HIV-1 infection on the prevalence of SMA (hemoglobin < 6.0 g/dl), parasitemia (parasites/microl), and high-density parasitemia (HDP, >or= 10 000 parasites/mul) was investigated in children <or= 2 years of age presenting at hospital with acute Plasmodium falciparum malaria in a rural holoendemic malaria transmission area of western Kenya. METHODS: Upon enrollment, a complete hematological and clinical evaluation was performed on all children. Malaria parasitemia was determined and children with acute P. falciparum malaria were evaluated for HIV-1 exposure and infection by two rapid serological antibody tests and HIV-1 DNA PCR, respectively. RESULTS: Relative to HIV-1(-) group (n = 194), the HIV-1(exp) (n = 100) and HIV-1(+) (n = 23) groups had lower hemoglobin concentrations (P < 0.001 and P < 0.001, respectively), while parasitemia and HDP were equivalent between the three groups. Multivariate analyses demonstrated that the risk of SMA was elevated in HIV-1(exp) children (odds ratio, 2.17; 95% confidence interval, 1.25-3.78; P < 0.01) and HIV-1(+) children (odds ratio, 8.71; 95% confidence interval, 3.37-22.51; P < 0.0001). The multivariate model further revealed that HIV-1 exposure or infection were not significantly associated with HDP. CONCLUSIONS: Results presented here demonstrate that both HIV-1 exposure and HIV-1 infection are associated with increased prevalence of SMA during acute P. falciparum infection, independent of parasite density.

Acute Disease↗

PubMed2006

Acquisition of hemozoin by monocytes down-regulates interleukin-12 p40 (IL-12p40) transcripts and circulating IL-12p70 through an IL-10-dependent mechanism: in vivo and in vitro findings in severe malarial anemia.

Severe malarial anemia (SMA) is a primary cause of morbidity and mortality in immune-naïve infants and young children residing in areas of holoendemic Plasmodium falciparum transmission. Although the immunopathogenesis of SMA is largely undefined, we have previously shown that systemic interleukin-12 (IL-12) production is suppressed during childhood blood-stage malaria. Since IL-10 and tumor necrosis factor alpha (TNF-alpha) are known to decrease IL-12 synthesis in a number of infectious diseases, altered transcriptional regulation of these inflammatory mediators was investigated as a potential mechanism for IL-12 down-regulation. Ingestion of naturally acquired malarial pigment (hemozoin [PfHz]) by monocytes promoted the overproduction of IL-10 and TNF-alpha relative to the production of IL-12, which correlated with an enhanced severity of malarial anemia. Experiments with cultured peripheral blood mononuclear cells (PBMC) and CD14(+) cells from malaria-naïve donors revealed that physiological concentrations of PfHz suppressed IL-12 and augmented IL-10 and TNF-alpha by altering the transcriptional kinetics of IL-12p40, IL-10, and TNF-alpha, respectively. IL-10 neutralizing antibodies, but not TNF-alpha antibodies, restored PfHz-induced suppression of IL-12. Blockade of IL-10 and the addition of recombinant IL-10 to cultured PBMC from children with SMA confirmed that IL-10 was responsible for malaria-induced suppression of IL-12. Taken together, these results demonstrate that PfHz-induced up-regulation of IL-10 is responsible for the suppression of IL-12 during malaria.

Anemia↗

PubMed2006

Anopheles gambiae (Diptera: Culicidae) oviposition in response to agarose media and cultured bacterial volatiles.

Anopheles gambiae s.s. Giles accepted a range of agarose gels, varying from 0.5 to 8% (wt:vol), for oviposition; laid more eggs on 0.5% agarose gels than on moist filter paper or on drier agarose; and laid equal numbers of eggs on 0.5% agarose gels and distilled water. Larvae hatched on agarose gel substrates and crawled onto the surface of moist agarose gels, but they tended only to burst the egg cap and remain within the egg case on drier gels. A mixture of cultured bacteria, originating from a natural larval habitat of An. gambaiae s.s. in western Kenya, was classified by 16S rDNA sequence analysis, and then this mixture or individual colonies from it was used as odor sources in ovipositional experiments with agarose substrates. Of 61 sequences from a mixed clone sequence library, most (78%) were Pseudomonas strains, whereas the remainder were Stenotrophomonas, Enterobacter, Pantoea, Klebsiella, Acinetobacter, Aeromonas, and Bacillus. Oviposition was significantly reduced when mixtures of bacterial colonies of these strains, or a lawn of colonies of a field isolate of S. maltophilia, was presented. Oviposition was neither reduced nor enhanced when field isolates of Pseudomonas putida or Pseudomonas alcaligenes colonies were presented. These results suggest that gravid An. gambiae females are sensitive to bacterial-derived odors emanating from cultured bacteria from natural larval habitats and that some bacterial odors may be repellent.

Animals↗

PubMed2006

Importance of algal biomass to growth and development of Anopheles gambiae larvae.

We conducted experiments to investigate the importance of algal food resources for larval growth and adult emergence of Anopheles gambiae Giles s.s. in simulated larval habitats in Kenya, and in greenhouse and laboratory microcosms in the United States. In the first experiment, we used shading to reduce algal biomass, and because algal production and larval development might be a function of underlying soil nutrients, we crossed sun-shade treatments with soils of two distinct types collected near larval habitats. Shading reduced pupation rates and total adult biomass of An. gambiae by approximately 50%. Soil type had no significant effect on mosquito production, but it did significantly affect concentrations of phosphorus and chlorophyll a in the surface microlayer. In a subsequent experiment conducted in the greenhouse to reduce temperature differences found between the shaded and sunlit treatments, <1% of larvae in the shaded treatments reached the pupal stage. There was a marked reduction of chlorophyll a levels as a function of shading and larval density. In a third experiment, larvae receiving material harvested from sunlit surface microlayers performed as well as those receiving liver powder, whereas those receiving surface microlayer from shaded habitats suffered >90% mortality and failed to pupate. In a fourth experiment, glucose was added to shaded microcosms to stimulate bacterial activity in the absence of algae. Bacterial growth rates were 2 to 3 times higher, and larval development was enhanced in glucose-amended treatments. However, pupation rates and adult weights in glucose-amended shaded microcosms were still poor compared with those in nonamended sunlit microcosms. Overall, these results demonstrate the importance of algal biomass in the surface microlayers of larval habitats to development and adult production of An. gambiae.

Animal Feed↗

PubMed2006

Evaluation of potential role of Anopheles ziemanni in malaria transmission in western Kenya.

Observations of considerable numbers of Anopheles ziemanni Grunberg resting inside human dwellings in Ahero, western Kenya, raised the question of its status in malaria transmission. To address this question, samples of this species were tested for Plasmodium falciparum infection rates and blood-feeding pattern, and data were compared with those of known vectors in the area. Although no An. ziemanni mosquitoes were infected with P. falciparum sporozoites, the proportions of this mosquito species among all anophelines captured and its human blood index compared well with those of other vectors, suggesting a possible role in the transmission of malaria. Additional studies, including both indoor- and outdoor-resting mosquito populations as well as incorporating laboratory-based parasite susceptibility tests should clarify the situation.

Animals↗

PubMed2006

Distribution, description, and local knowledge of larval habitats of Anopheles gambiae s.l. in a village in western Kenya.

A sampling census revealed 104 aquatic habitats of 6 types for Anopheles gambiae s.l. larvae in a village in western Kenya, namely burrow pits, drainage channels, livestock hoof prints, rain pools, tire tracks, and pools in streambeds. Most habitats were created by human activity and were highly clustered in dispersion pattern within the village landscape. Landscape analysis revealed that six of forty-seven 0.09 km(2) cells superimposed over the village harbored 65% of all habitats. Focus group discussions and in-depth interviews with villagers revealed the extent of knowledge of the village residents of larval habitats, mosquito sources in the local environment, and what might be done to prevent mosquito breeding. Participants did not associate specific habitats with anopheline larvae, expressed reluctance to eliminate habitats because they were sources of domestic water supply, but indicated willingness to participate in a source reduction program if support were available.

Animals↗

PubMed2006

Pupal habitat productivity of Anopheles gambiae complex mosquitoes in a rural village in western Kenya.

The productivity of larval habitats of the malaria vector Anopheles gambiae for pupae (the stage preceding adult metamorphosis) is poorly known, yet adult emergence from habitats is the primary determinant of vector density. To assess it, we used absolute sampling methods in four studies involving daily sampling for 25 days in 6 habitat types in a village in western Kenya. Anopheles gambiae s.s. comprised 82.5% of emergent adults and Anopheles arabiensis the remainder. Pupal production occurred from a subset of habitats, primarily soil burrow pits, and was discontinuous in time, even when larvae occupied all habitats continuously. Habitat stability was positively associated with pupal productivity. In a dry season, pupal productivity was distributed between burrow pits and pools in streambeds. Overall, these data support the notion that source reduction measures against recognizably productive habitats would be a useful component of an integrated management program for An. gambiae in villages.

Animals↗

PubMed2006

Parasitemia, anemia, and malarial anemia in infants and young children in a rural holoendemic Plasmodium falciparum transmission area.

Malarial anemia (MA) is a multifactorial disease for which the complex etiological basis is only partially defined. The association of clinical, nutritional, demographic, and socioeconomic factors with parasitemia, anemia, and MA was determined for children presenting at a hospital in a holoendemic area of Plasmodium falciparum transmission in western Kenya. Parasitemia was not associated with malaria disease severity. In univariate logistic regression, fever was significantly associated with parasitemia, and wasting was associated with increased presentation of MA. Caretaker's level of education and occupation were significantly correlated with parasitemia, anemia, and MA. Housing structure was also significantly associated with parasitemia and anemia. Bed net use was protective against parasitemia but not anemia or MA. Multivariate logistic regression models demonstrated that fever, mother's occupation, and bed net use were associated with parasitemia. In the current study, none of the factors were associated with anemia or MA in the multivariate models.

Anemia↗

PubMed2006

Association of FCgamma receptor IIA (CD32) polymorphism with malarial anemia and high-density parasitemia in infants and young children.

Protective immunity against Plasmodium falciparum is partially mediated through binding of malaria-specific IgG antibodies to Fcgamma receptors. Polymorphic variability in Fcgamma RIIa (H/R-131) is associated with differential binding of IgG subtypes and malaria disease outcomes. However, the role of Fcgamma RIIa-131 variability in conditioning susceptibility to severe malarial anemia, the primary manifestation of severe malaria in holoendemic P. falciparum transmission areas, is largely undefined. Thus, Fcgamma RIIa-H131R polymorphism was investigated in 493 children who came to a hospital with acute malaria. Variation in Fcgamma RIIa-131 was not significantly associated with severe malarial anemia (hemoglobin [Hb] < 6.0 g/dL) or malaria anemia (Hb < 8.0 g/dL). However, relative to the heterozygous genotype, homozygotes for the R131 alleles were protected against high-density parasitemia (>or= 10,000 parasites/microL; odds ratio [OR] = 0.58, 95% confidence interval [CI] = 0.37-0.92, P = 0.02), while homozygotes for the H131 alleles were mildly protective (OR = 0.71, 95% CI = 0.45-1.13, P = 0.14). Additional multivariate analyses showed that infection with human immunodeficiency virus type 1 did not influence the associations between FcgammaRIIa-H131R polymorphism and malaria disease outcomes. Genotypic results presented here parallel data illustrating that parasite density is unrelated to the severity of anemia in children with acute malaria. Thus, although homozygosity for the R131 allele protects against high-density parasitemia, FcgammaRIIa-131 polymorphism does not protect against malaria anemia.

Anemia↗

PubMed2006

Suppression of RANTES in children with Plasmodium falciparum malaria.

Severe malarial anemia (MA) is the primary manifestation of severe malaria among children in areas of holoendemic Plasmodium falciparum transmission. Although overproduction of inflammatory-derived cytokines are implicated in the immunopathogenesis of severe MA, chemokines such as regulated on activation, normal T-cell expressed and secreted (RANTES, CCL5) are largely unexplored in childhood malaria. We found that RANTES is decreased during severe MA (p<0.01), and associated with suppression of erythropoiesis (p<0.05) and malaria-induced thrombocytopenia (p<0.05). These findings suggest that thrombocytopenia may be a source of reduced RANTES which may contribute, at least in part, to suppression of erythropoiesis in children with malarial anemia.

Animals↗

PubMed2005

Household based treatment of drinking water with flocculant-disinfectant for preventing diarrhoea in areas with turbid source water in rural western Kenya: cluster randomised controlled trial.

OBJECTIVE: To compare the effect on prevalence of diarrhoea and mortality of household based treatment of drinking water with flocculant-disinfectant, sodium hypochlorite, and standard practices in areas with turbid water source in Africa. DESIGN: Cluster randomised controlled trial over 20 weeks. SETTING: Family compounds, each containing several houses, in rural western Kenya. PARTICIPANTS: 6650 people in 605 family compounds. INTERVENTION: Water treatment: flocculant-disinfectant, sodium hypochlorite, and usual practice (control). MAIN OUTCOME MEASURES: Prevalence of diarrhoea and all cause mortality. Escherichia coli concentration, free residual chlorine concentration, and turbidity in household drinking water as surrogates for effectiveness of water treatment. RESULTS: In children < 2 years old, compared with those in the control compounds, the absolute difference in prevalence of diarrhoea was -25% in the flocculant-disinfectant arm (95% confidence interval -40 to -5) and -17% in the sodium hypochlorite arm (-34 to 4). In all age groups compared with control, the absolute difference in prevalence was -19% in the flocculant-disinfectant arm (-34 to -2) and -26% in the sodium hypochlorite arm (-39 to -9). There were significantly fewer deaths in the intervention compounds than in the control compounds (relative risk of death 0.58, P = 0.036). Fourteen per cent of water samples from control compounds had E coli concentrations < 1 CFU/100 ml compared with 82% in flocculant-disinfectant and 78% in sodium hypochlorite compounds. The mean turbidity of drinking water was 8 nephelometric turbidity units (NTU) in flocculant-disinfectant households, compared with 55 NTU in the two other compounds (P < 0.001). CONCLUSIONS: In areas of turbid water, flocculant-disinfectant was associated with a significant reduction in diarrhoea among children < 2 years. This health benefit, combined with a significant reduction in turbidity, suggests that the flocculant-disinfectant is well suited to areas with highly contaminated and turbid water.

Adolescent↗

PubMed2005

Effect of sustained insecticide-treated bed net use on all-cause child mortality in an area of intense perennial malaria transmission in western Kenya.

We present results from a study conducted in western Kenya where all-cause child mortality was assessed among a population with high levels of sustained insecticide-treated bed net (ITN) use for up to six years. Although ITNs were associated with significant reductions in all-cause mortality among infants 1-11 months old, there was no difference in the rate of all-cause mortality among children 12-59 months old with ITNs for 2-4 years, compared historically with children from villages without ITNs, after controlling for seasonality and underlying child mortality across calendar years (adjusted hazard ratio [AHR] = 0.91, 95% confidence interval [CI] = 0.77-1.07). There was no increase in the proportion of child deaths at older ages (12-59 months old) of all child deaths within villages with ITNs for 5-6 years (48.1%) compared historically with villages without ITNs (47.9%), after controlling for seasonality (AHR = 1.03, P = 0.834). We find no evidence that sustained ITN use increased the risk of mortality in older children in this area of intense perennial malaria transmission.

Animals↗

PubMed2005

Health and demographic surveillance in rural western Kenya: a platform for evaluating interventions to reduce morbidity and mortality from infectious diseases.

We established a health and demographic surveillance system in a rural area of western Kenya to measure the burden of infectious diseases and evaluate public health interventions. After a baseline census, all 33,990 households were visited every four months. We collected data on educational attainment, socioeconomic status, pediatric outpatient visits, causes of death in children, and malaria transmission. The life expectancy at birth was 38 years, the infant mortality rate was 125 per 1000 live births, and the under-five mortality rate was 227 per 1,000 live births. The increased mortality rate in younger men and women suggests high human immunodeficiency virus/acquired immunodeficiency syndrome-related mortality in the population. Of 5,879 sick child visits, the most frequent diagnosis was malaria (71.5%). Verbal autopsy results for 661 child deaths (1 month to <12 years) implicated malaria (28.9%) and anemia (19.8%) as the most common causes of death in children. These data will provide a basis for generating further research questions, developing targeted interventions, and evaluating their impact.

Adolescent↗