Background: Control of the Anopheline mosquito vectors of malaria by use of insecticides has been... more 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.
The growth and development of Anopheles gambiae Giles larvae were studied in artiÞcial habitats i... more The growth and development of Anopheles gambiae Giles larvae were studied in artiÞcial habitats in western Kenya. Larvae responded to increasing densities by extending their development time and by emerging as smaller adults, although survival was not signiÞcantly affected. Addition of nutrients in the form of cow dung collected near the study site had no impact on larval growth and development. Regression analysis showed that female development time increased by 0.020 d and female dry mass decreased by 0.74 g with each additional larva. By Þtting the data to the pupation window model, the estimated minimum dry mass to achieve pupation was 0.130 mg and the estimated minimum time to pupation was 5 d. The most likely food source for An. gambiae larvae was algal growth, which was signiÞcantly reduced by the presence of larvae. Bacterial densities were not signiÞcantly affected by the presence of larvae although total bacteria counts were lower at the higher densities indicating they may provide a secondary food source when algal resources are depleted. Similarly, the levels of nitrogen and phosphorus in the habitats were not signiÞcantly affected by the presence of larvae although there was evidence of decreasing nitrogen levels occurring with increasing larval densities suggesting that nitrogen may be a limiting resource in the larval environment. The data indicate that competition within the larval environment may indirectly regulate An. gambiae populations by reducing adult body size, which may in turn reduce adult survivorship and fecundity. The potential impact of density-dependent interactions among An. gambiae larvae on the transmission of Plasmodium falciparum is discussed.
The American Journal of Tropical Medicine and Hygiene, Apr 1, 2003
Spatial analyses of the effect of insecticide (permethrin)-treated bed nets (ITNs) on nearby hous... more Spatial analyses of the effect of insecticide (permethrin)-treated bed nets (ITNs) on nearby households both with and without ITNs was performed in the context of a large-scale, group-randomized, controlled mortality trial in Asembo, western Kenya. Results illustrate a protective effect of ITNs on compounds lacking ITNs located within 300 meters of compounds with ITNs for child mortality, moderate anemia, high-density parasitemia, and hemoglobin levels. This community effect on nearby compounds without nets is approximately as strong as the effect observed within villages with ITNs. This implies that in areas with intense malaria transmission with high ITN coverage, the primary effect of insecticide-treated nets is via area-wide effects on the mosquito population and not, as commonly supposed, by simple imposition of a physical barrier protecting individuals from biting. The strength of the community effect depended upon the proportion of nearby compounds with treated nets. To maximize their public health impact, high coverage with treated nets is essential.
The American Journal of Tropical Medicine and Hygiene, Apr 1, 2003
A group-randomized controlled trial of insecticide (permethrin)-treated bed nets (ITNs) was condu... more A group-randomized controlled trial of insecticide (permethrin)-treated bed nets (ITNs) was conducted in an area of high perennial malaria transmission in western Kenya to test the effect of ITNs on all-cause mortality in children 1-59 months of age. Child deaths were monitored over a two-year period by biannual household census in deaths occurred in children 1-59 months followed for 35,932 child-years. Crude mortality rates/1,000 child-years were 51.9 versus 43.9 in control and ITN villages in children 1-59 months old. The protective efficacy (PE) (95% confidence interval) adjusted for age, study year, study site, and season was 16% (6-25%). Corresponding figures in 1-11-and 12-59-month-old children in control and ITN villages were 133.3 versus 102.3, PE ס 23% (11-34%) and 31.1 versus 28.7, PE ס 7% (-6-19%). The numbers of lives saved/1,000 child-years were 8, 31, and 2 for the groups 1-59, 1-11, and 12-59 months old, respectively. Stratified analysis by time to insecticide re-treatment showed that the PE of ITNs re-treated per study protocol (every six months) was 20% (10-29%), overall and 26% (12-37%) and 14% (−1-26%) in 1-11-and 12-59-month-old children, respectively. ITNs prevent approximately one in four infant deaths in areas of intense perennial malaria transmission, but their efficacy is compromised if re-treatment is delayed beyond six months.
The American Journal of Tropical Medicine and Hygiene, Apr 1, 2003
The effect of insecticide (permethrin)-treated bed nets (ITNs) on the spatial distribution of mal... more The effect of insecticide (permethrin)-treated bed nets (ITNs) on the spatial distribution of malaria vectors in neighboring villages lacking ITNs was studied during a randomized controlled trial of ITNs in western Kenya. There was a trend of decreased abundance of Anopheles gambiae with decreasing distance from intervention villages both before (P ס 0.027) and after (P ס 0.002) introduction of ITNs, but this trend was significantly stronger after ITNs were introduced (P ס 0.05). For An. funestus, no pre-intervention trend was observed (P ס 0.373), but after the intervention, a trend of decreased abundance with closer proximity to intervention compounds developed (P ס 0.027). Reduction in mosquito populations in villages lacking ITNs was most apparent in compounds located within 600 meters of intervention villages. Sporozoite infection rates decreased in control areas following the introduction of ITNs (P < 0.001 for both species), but no spatial association was detected between sporozoite rates and distance to nearest intervention village. We conclude that high coverage of ITNs is associated with a community-wide suppression of mosquito populations that is detectable in neighboring villages lacking ITNs, thereby affording individuals residing in these villages some protection against malaria.
The American Journal of Tropical Medicine and Hygiene, Apr 1, 2003
This paper describes the study design and methods used in a large community-based, group-randomiz... more This paper describes the study design and methods used in a large community-based, group-randomized, controlled trial of permethrin-treated bed nets (ITNs) in an area with intense, perennial malaria transmission in western Kenya conducted between 1996 and 1999. A multi-disciplinary framework was used to explore the efficacy of ITNs in the reduction of all-cause mortality in children less than five years old, the clinical, entomologic, immunologic, and economic impact of ITNs, the social and behavioral determinants of ITN use, and the use of a geographic information system to allow for spatial analyses of these outcomes. Methodologic difficulties encountered in such large-scale field trials are discussed.
The American Journal of Tropical Medicine and Hygiene, Apr 1, 2003
The fifth, and probably last, large-scale, group-randomized, controlled trial of insecticide (per... more The fifth, and probably last, large-scale, group-randomized, controlled trial of insecticide (permethrin)treated bed nets (ITNs) showed that ITNs are efficacious in reducing all-cause post-neonatal mortality in an area of intense, perennial malaria transmission. The trial helped to define pregnant women and infants as target groups for this intervention in high transmission settings. High population coverage with ITNs in both target and non-target groups may be critical to enhance health and survival in pregnant women and infants. The proportion of households with ITNs (coverage), the proportion of individuals properly deploying ITNs each night (adherence), and the proportion of nets properly treated with insecticide (treatment) are the three key determinants of effectiveness of large-scale ITN programs. These three simple outcomes should serve as the basis for program objectives and monitoring and evaluation efforts. Coverage effects and economic analysis support the proposition that ITNs may be viewed as a public good, worthy of public support. Research should continue to improve the intervention tools (the net, the insecticide, and methods for durable treatment and re-treatment) and their deployment.
The American Journal of Tropical Medicine and Hygiene, Aug 1, 2007
The merozoite surface protein-1 (MSP-1) is a blood stage antigen currently being tested as a vacc... more The merozoite surface protein-1 (MSP-1) is a blood stage antigen currently being tested as a vaccine against Plasmodium falciparum malaria. Determining the MSP-1 19 haplotype(s) present during infection is essential for assessments of MSP-1 vaccine efficacy and studies of protective immunity in human populations. The C-terminal fragment (MSP-1 19 ) has four predominant haplotypes based on point mutations resulting in non-synonymous amino acid changes: E-TSR (PNG-MAD20 type), E-KNG (Uganda-PA type), Q-KNG (Wellcome type), and Q-TSR (Indo type). Current techniques using direct DNA sequencing are laborious and expensive. We present an MSP-1 19 allele-specific polymerase chain reaction (PCR)/ligase detection reaction-fluorescent microsphere assay (LDR-FMA) that allows simultaneous detection of the four predominant MSP-1 19 haplotypes with a sensitivity and specificity comparable with other molecular methods and a semi-quantitative determination of haplotype contribution in mixed infections. Application of this method is an inexpensive, accurate, and high-throughput alternative to distinguish the predominant MSP-1 19 haplotypes in epidemiologic studies.
Effect of different netting fabrics impregnated with varying doses of a stabilized natural pyreth... more Effect of different netting fabrics impregnated with varying doses of a stabilized natural pyrethinsemulsifiable concentrate formulation on bio-efficacy against Anopheles gambiae s.l. was investigated. Three-day-old female An. gambiae s.l. mosquitoes were exposed for three minutes on netting fabrics of nylon, polyester and cotton impregnated with the pyrethrins-formulation at 100mg/m 2 , 250mg/m 2 , 500mg/m 2 or 1000mg/m 2 . Results demonstrated that, there was an overall mosquito knockdown of 45.6% and mortality of 14.0% on cotton as compared to 78.3% knockdown and 61.3% mortality on polyester and 90.4% on both knockdown and mortality on nylon fabric at 60 minutes and 24 hours post-treatment, respectively. There was a corresponding increase in knockdown and mortality with increasing dosage, though the magnitude depended on the impregnated fabric. The dosage of the pyrethrins-formulation required to achieve 80% mortality on mosquitoes when applied on a nylon net was 200mg/m 2 relative to polyester fabric that needed 375mg/m 2 . It was, however, not possible to achieve the 80% mortality level with the impregnated cotton fabric at the test doses. These results demonstrate the significance of the intrinsic fabric properties and dosage level of the insecticide used for impregnation on the bio-efficay of natural pyrethrins in insecticide-treated nets (ITNs). Findings further show that the pyrethrins formulation was most suitable for treatment of nylon and polyester fabrics with a rather poor performance on cotton nets. These results are considered encouraging especially for efficient use of natural pyrethrins-formulation in ITNs.
Background: Following the development of resistance to anti-malarial mono-therapies, malaria ende... more Background: Following the development of resistance to anti-malarial mono-therapies, malaria endemic countries in Africa now use artemisinin-based combination therapy (ACT) as recommended first-line treatment for uncomplicated malaria. Patients' adherence to ACT is an important factor to ensure treatment efficacy, as well as to reduce the likelihood of parasite resistance to these drugs. This study reports adherence to a specific ACT, artemether-lumefantrine (AL), under conditions of routine clinical practice in Kenya. Method: The study was undertaken in Garissa and Bunyala districts among outpatients of five government health facilities. Patients treated with AL were visited at home four days after having been prescribed the drug. Respondents (patients ≥ 15 years and caregivers of patients < 15 years) were interviewed using a standardized questionnaire, AL blister packs were physically inspected and the adherence status of patients was then recorded. Multivariate logistic regression modelling was used to determine predictors of adherence. Results: Of the 918 patients included in the study, 588 (64.1%) were 'probably adherent', 291 (31.7%) were 'definitely non-adherent' and 39 (4.2%) were 'probably non-adherent'. Six factors were found to be significant predictors of adherence: patient knowledge of the ACT dosing regimen (odds ratio (OR) = 1.76; 95% CI = 1.32-2.35), patient age (OR = 1.65; 95% CI = 1.02-1.85), respondent age (OR = 1.37; 95% CI = 1.10-2.48), whether a respondent had seen AL before (OR = 1.46; 95% CI = 1.08-1.98), whether a patient had reported dislikes to AL (OR = 0.62 95% CI = 0.47-0.82) and whether a respondent had waited more than 24 hours to seek treatment (OR = 0.73; 95% CI = 0.54-0.99). Conclusion: Overall, adherence to AL was found to be low in both Garissa and Bunyala districts, with patient knowledge of the AL dosing regimen found to be the strongest predictor of adherence. Interventions aimed at increasing community awareness of the AL dosing regimen, use of child friendly formulations and improving health workers' prescribing practices are likely to ensure higher adherence to AL and eventual treatment success.
Background: Operational vector sampling methods lack standardization, making quantitative compari... more Background: Operational vector sampling methods lack standardization, making quantitative comparisons of malaria transmission across different settings difficult. Human landing catch (HLC) is considered the research gold standard for measuring human-mosquito contact, but is unsuitable for large-scale sampling. This study assessed mosquito catch rates of CDC light trap (CDC-LT), Ifakara tent trap (ITT), window exit trap (WET), pot resting trap (PRT), and box resting trap (BRT) relative to HLC in western Kenya to 1) identify appropriate methods for operational sampling in this region, and 2) contribute to a larger, overarching project comparing standardized evaluations of vector trapping methods across multiple countries. Methods: Mosquitoes were collected from June to July 2009 in four districts: Rarieda, Kisumu West, Nyando, and Rachuonyo. In each district, all trapping methods were rotated 10 times through three houses in a 3 × 3 Latin Square design. Anophelines were identified by morphology and females classified as fed or non-fed. Anopheles gambiae s.l. were further identified as Anopheles gambiae s.s. or Anopheles arabiensis by PCR. Relative catch rates were estimated by negative binomial regression.
The status of resistance was investigated in Anopheles gambiae sensu lato and An. funestus (Dipte... more The status of resistance was investigated in Anopheles gambiae sensu lato and An. funestus (Diptera: Culicidae) mosquitoes from western Kenya to four classes of insecticides approved by World Health Organization for indoor residual spraying. The prevalence of the knockdown-resistance (kdr) mutation associated with resistance to pyrethroids and DDT was determined in An. gambiae s.l.. Standard World Health Organization diagnostic bioassay kits for DDT (an organochlorine), fenitrothion (an organophosphate), bendiocarb (a carbamate), and the pyrethoirds, lambdacyhalothrin and permethrin, were used. Knockdown every 10 min and mortality 24 h after exposure were noted. Controls not treated with insecticides and with the susceptible An. gambiae KISUMU strain were included in the bioassays. The presence of the kdr gene was determined using a standard diagnostic polymerase chain reaction assay. Over 98% mortality was observed for tests with all insecticides for both An. gambiae s.l. and An. funestus. Knockdown rates were not significantly different between An. gambiae s.l. and the KISUMU strain control. 50% and 95% knockdown times were either slightly lower than those for the KISUMU strain or higher by factors of less than 1.6. The mean frequency of the East African kdr mutation was 24.7% in An. gambiae sensu strictu. Based on conventional criteria where susceptibility is defined by mortality rates >98% 24 h after exposure, no evidence for resistance was found, implying that vector control measures employing any of the insecticides tested would be unhampered by resistance. The observed frequencies of the kdr mutation do not appear to compromise the effectiveness of the insecticides. The need for continuous monitoring of the status of insecticide resistance and of the impact of any observed resistance on the efficacy of vector control programs employing insecticides is apparent.
More focus is given to mosquito larval control due to the necessity to use several control techni... more 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.
We determined the nutritional status of children less than five years of age in an area in rural ... more We determined the nutritional status of children less than five years of age in an area in rural western Kenya with intense malaria transmission, a high prevalence of severe anemia and human immunodeficiency virus, and high infant and under-five mortality (176/1,000 and 259/1,000). No information is available on the prevalence of malnutrition in this area. Three cross-sectional surveys were conducted between 1996 and 1998 to monitor the effect of insecticide-treated bed nets on child morbidity. Anthropometric indices are presented for 2,103 children collected prior to and during intervention (controls only). The prevalence of stunting (Z-scores for height-for-age [HAZ] <−2), wasting (Z-scores for weight-for-height [WHZ] <−2) and being underweight (Z-scores for weight-for-age [WAZ] <−2) was 30%, 4%, and 20%, respectively. This was severe (Z-score <−3) in 12% (stunting), 1% (wasting), and 5% (underweight) of the children. Few children less than three months of age were malnourished (<2%), but height-for-age and weight-forage deficits increased rapidly in children 3−18 months of age, and were greatest in children 18−23 months old (44% stunted and 34% underweight). While the mean HAZ and WAZ stabilized from 24 months of age onwards, they still remained substantially below the reference median with no evidence of catch-up growth. Malnutrition is likely to interact with infectious diseases, placing children 3−24 months of age at high risk of premature death in this area.
Information on the impact of insecticide (permethrin)-treated bed nets (ITNs) from randomized con... more Information on the impact of insecticide (permethrin)-treated bed nets (ITNs) from randomized controlled trials in areas of intense perennial malaria transmission is limited. As part of a large-scale, community-based, group-randomized controlled trial of the effect of ITNs on childhood mortality in a holoendemic area in western Kenya, we conducted three cross-sectional surveys in 60 villages to assess the impact of ITNs on morbidity in 1,890 children less than three years old. Children in ITN and control villages were comparable pre-intervention, but after the introduction of ITNs, children in intervention villages were less likely to have recently experienced illness requiring treatment (protective efficacy [95% confidence intervals] ס 15% [1−26%]), have an enlarged spleen (32% [20−43%]), be parasitemic (19% [11−27%]), have clinical malaria (44% [6−66%]), have moderately severe anemia (hemoglobin level < 7.0 g/dL; 39% [18−54%]), or have a pruritic body rash, presumably from reduced nuisance insect bites (38% [24−50%]). Use of ITNs was also associated with significantly higher mean weight-for-age Z-scores and mid-upper arm circumferences. There was no evidence, however, that ITNs reduced the risk of helminth infections, diarrhea, or upper or lower respiratory tract infections. The ITNs substantially reduced malaria-associated morbidity and improved weight gain in young children in this area of intense perennial malaria transmission.
Background: Control of the Anopheline mosquito vectors of malaria by use of insecticides has been... more 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.
The growth and development of Anopheles gambiae Giles larvae were studied in artiÞcial habitats i... more The growth and development of Anopheles gambiae Giles larvae were studied in artiÞcial habitats in western Kenya. Larvae responded to increasing densities by extending their development time and by emerging as smaller adults, although survival was not signiÞcantly affected. Addition of nutrients in the form of cow dung collected near the study site had no impact on larval growth and development. Regression analysis showed that female development time increased by 0.020 d and female dry mass decreased by 0.74 g with each additional larva. By Þtting the data to the pupation window model, the estimated minimum dry mass to achieve pupation was 0.130 mg and the estimated minimum time to pupation was 5 d. The most likely food source for An. gambiae larvae was algal growth, which was signiÞcantly reduced by the presence of larvae. Bacterial densities were not signiÞcantly affected by the presence of larvae although total bacteria counts were lower at the higher densities indicating they may provide a secondary food source when algal resources are depleted. Similarly, the levels of nitrogen and phosphorus in the habitats were not signiÞcantly affected by the presence of larvae although there was evidence of decreasing nitrogen levels occurring with increasing larval densities suggesting that nitrogen may be a limiting resource in the larval environment. The data indicate that competition within the larval environment may indirectly regulate An. gambiae populations by reducing adult body size, which may in turn reduce adult survivorship and fecundity. The potential impact of density-dependent interactions among An. gambiae larvae on the transmission of Plasmodium falciparum is discussed.
The American Journal of Tropical Medicine and Hygiene, Apr 1, 2003
Spatial analyses of the effect of insecticide (permethrin)-treated bed nets (ITNs) on nearby hous... more Spatial analyses of the effect of insecticide (permethrin)-treated bed nets (ITNs) on nearby households both with and without ITNs was performed in the context of a large-scale, group-randomized, controlled mortality trial in Asembo, western Kenya. Results illustrate a protective effect of ITNs on compounds lacking ITNs located within 300 meters of compounds with ITNs for child mortality, moderate anemia, high-density parasitemia, and hemoglobin levels. This community effect on nearby compounds without nets is approximately as strong as the effect observed within villages with ITNs. This implies that in areas with intense malaria transmission with high ITN coverage, the primary effect of insecticide-treated nets is via area-wide effects on the mosquito population and not, as commonly supposed, by simple imposition of a physical barrier protecting individuals from biting. The strength of the community effect depended upon the proportion of nearby compounds with treated nets. To maximize their public health impact, high coverage with treated nets is essential.
The American Journal of Tropical Medicine and Hygiene, Apr 1, 2003
A group-randomized controlled trial of insecticide (permethrin)-treated bed nets (ITNs) was condu... more A group-randomized controlled trial of insecticide (permethrin)-treated bed nets (ITNs) was conducted in an area of high perennial malaria transmission in western Kenya to test the effect of ITNs on all-cause mortality in children 1-59 months of age. Child deaths were monitored over a two-year period by biannual household census in deaths occurred in children 1-59 months followed for 35,932 child-years. Crude mortality rates/1,000 child-years were 51.9 versus 43.9 in control and ITN villages in children 1-59 months old. The protective efficacy (PE) (95% confidence interval) adjusted for age, study year, study site, and season was 16% (6-25%). Corresponding figures in 1-11-and 12-59-month-old children in control and ITN villages were 133.3 versus 102.3, PE ס 23% (11-34%) and 31.1 versus 28.7, PE ס 7% (-6-19%). The numbers of lives saved/1,000 child-years were 8, 31, and 2 for the groups 1-59, 1-11, and 12-59 months old, respectively. Stratified analysis by time to insecticide re-treatment showed that the PE of ITNs re-treated per study protocol (every six months) was 20% (10-29%), overall and 26% (12-37%) and 14% (−1-26%) in 1-11-and 12-59-month-old children, respectively. ITNs prevent approximately one in four infant deaths in areas of intense perennial malaria transmission, but their efficacy is compromised if re-treatment is delayed beyond six months.
The American Journal of Tropical Medicine and Hygiene, Apr 1, 2003
The effect of insecticide (permethrin)-treated bed nets (ITNs) on the spatial distribution of mal... more The effect of insecticide (permethrin)-treated bed nets (ITNs) on the spatial distribution of malaria vectors in neighboring villages lacking ITNs was studied during a randomized controlled trial of ITNs in western Kenya. There was a trend of decreased abundance of Anopheles gambiae with decreasing distance from intervention villages both before (P ס 0.027) and after (P ס 0.002) introduction of ITNs, but this trend was significantly stronger after ITNs were introduced (P ס 0.05). For An. funestus, no pre-intervention trend was observed (P ס 0.373), but after the intervention, a trend of decreased abundance with closer proximity to intervention compounds developed (P ס 0.027). Reduction in mosquito populations in villages lacking ITNs was most apparent in compounds located within 600 meters of intervention villages. Sporozoite infection rates decreased in control areas following the introduction of ITNs (P < 0.001 for both species), but no spatial association was detected between sporozoite rates and distance to nearest intervention village. We conclude that high coverage of ITNs is associated with a community-wide suppression of mosquito populations that is detectable in neighboring villages lacking ITNs, thereby affording individuals residing in these villages some protection against malaria.
The American Journal of Tropical Medicine and Hygiene, Apr 1, 2003
This paper describes the study design and methods used in a large community-based, group-randomiz... more This paper describes the study design and methods used in a large community-based, group-randomized, controlled trial of permethrin-treated bed nets (ITNs) in an area with intense, perennial malaria transmission in western Kenya conducted between 1996 and 1999. A multi-disciplinary framework was used to explore the efficacy of ITNs in the reduction of all-cause mortality in children less than five years old, the clinical, entomologic, immunologic, and economic impact of ITNs, the social and behavioral determinants of ITN use, and the use of a geographic information system to allow for spatial analyses of these outcomes. Methodologic difficulties encountered in such large-scale field trials are discussed.
The American Journal of Tropical Medicine and Hygiene, Apr 1, 2003
The fifth, and probably last, large-scale, group-randomized, controlled trial of insecticide (per... more The fifth, and probably last, large-scale, group-randomized, controlled trial of insecticide (permethrin)treated bed nets (ITNs) showed that ITNs are efficacious in reducing all-cause post-neonatal mortality in an area of intense, perennial malaria transmission. The trial helped to define pregnant women and infants as target groups for this intervention in high transmission settings. High population coverage with ITNs in both target and non-target groups may be critical to enhance health and survival in pregnant women and infants. The proportion of households with ITNs (coverage), the proportion of individuals properly deploying ITNs each night (adherence), and the proportion of nets properly treated with insecticide (treatment) are the three key determinants of effectiveness of large-scale ITN programs. These three simple outcomes should serve as the basis for program objectives and monitoring and evaluation efforts. Coverage effects and economic analysis support the proposition that ITNs may be viewed as a public good, worthy of public support. Research should continue to improve the intervention tools (the net, the insecticide, and methods for durable treatment and re-treatment) and their deployment.
The American Journal of Tropical Medicine and Hygiene, Aug 1, 2007
The merozoite surface protein-1 (MSP-1) is a blood stage antigen currently being tested as a vacc... more The merozoite surface protein-1 (MSP-1) is a blood stage antigen currently being tested as a vaccine against Plasmodium falciparum malaria. Determining the MSP-1 19 haplotype(s) present during infection is essential for assessments of MSP-1 vaccine efficacy and studies of protective immunity in human populations. The C-terminal fragment (MSP-1 19 ) has four predominant haplotypes based on point mutations resulting in non-synonymous amino acid changes: E-TSR (PNG-MAD20 type), E-KNG (Uganda-PA type), Q-KNG (Wellcome type), and Q-TSR (Indo type). Current techniques using direct DNA sequencing are laborious and expensive. We present an MSP-1 19 allele-specific polymerase chain reaction (PCR)/ligase detection reaction-fluorescent microsphere assay (LDR-FMA) that allows simultaneous detection of the four predominant MSP-1 19 haplotypes with a sensitivity and specificity comparable with other molecular methods and a semi-quantitative determination of haplotype contribution in mixed infections. Application of this method is an inexpensive, accurate, and high-throughput alternative to distinguish the predominant MSP-1 19 haplotypes in epidemiologic studies.
Effect of different netting fabrics impregnated with varying doses of a stabilized natural pyreth... more Effect of different netting fabrics impregnated with varying doses of a stabilized natural pyrethinsemulsifiable concentrate formulation on bio-efficacy against Anopheles gambiae s.l. was investigated. Three-day-old female An. gambiae s.l. mosquitoes were exposed for three minutes on netting fabrics of nylon, polyester and cotton impregnated with the pyrethrins-formulation at 100mg/m 2 , 250mg/m 2 , 500mg/m 2 or 1000mg/m 2 . Results demonstrated that, there was an overall mosquito knockdown of 45.6% and mortality of 14.0% on cotton as compared to 78.3% knockdown and 61.3% mortality on polyester and 90.4% on both knockdown and mortality on nylon fabric at 60 minutes and 24 hours post-treatment, respectively. There was a corresponding increase in knockdown and mortality with increasing dosage, though the magnitude depended on the impregnated fabric. The dosage of the pyrethrins-formulation required to achieve 80% mortality on mosquitoes when applied on a nylon net was 200mg/m 2 relative to polyester fabric that needed 375mg/m 2 . It was, however, not possible to achieve the 80% mortality level with the impregnated cotton fabric at the test doses. These results demonstrate the significance of the intrinsic fabric properties and dosage level of the insecticide used for impregnation on the bio-efficay of natural pyrethrins in insecticide-treated nets (ITNs). Findings further show that the pyrethrins formulation was most suitable for treatment of nylon and polyester fabrics with a rather poor performance on cotton nets. These results are considered encouraging especially for efficient use of natural pyrethrins-formulation in ITNs.
Background: Following the development of resistance to anti-malarial mono-therapies, malaria ende... more Background: Following the development of resistance to anti-malarial mono-therapies, malaria endemic countries in Africa now use artemisinin-based combination therapy (ACT) as recommended first-line treatment for uncomplicated malaria. Patients' adherence to ACT is an important factor to ensure treatment efficacy, as well as to reduce the likelihood of parasite resistance to these drugs. This study reports adherence to a specific ACT, artemether-lumefantrine (AL), under conditions of routine clinical practice in Kenya. Method: The study was undertaken in Garissa and Bunyala districts among outpatients of five government health facilities. Patients treated with AL were visited at home four days after having been prescribed the drug. Respondents (patients ≥ 15 years and caregivers of patients < 15 years) were interviewed using a standardized questionnaire, AL blister packs were physically inspected and the adherence status of patients was then recorded. Multivariate logistic regression modelling was used to determine predictors of adherence. Results: Of the 918 patients included in the study, 588 (64.1%) were 'probably adherent', 291 (31.7%) were 'definitely non-adherent' and 39 (4.2%) were 'probably non-adherent'. Six factors were found to be significant predictors of adherence: patient knowledge of the ACT dosing regimen (odds ratio (OR) = 1.76; 95% CI = 1.32-2.35), patient age (OR = 1.65; 95% CI = 1.02-1.85), respondent age (OR = 1.37; 95% CI = 1.10-2.48), whether a respondent had seen AL before (OR = 1.46; 95% CI = 1.08-1.98), whether a patient had reported dislikes to AL (OR = 0.62 95% CI = 0.47-0.82) and whether a respondent had waited more than 24 hours to seek treatment (OR = 0.73; 95% CI = 0.54-0.99). Conclusion: Overall, adherence to AL was found to be low in both Garissa and Bunyala districts, with patient knowledge of the AL dosing regimen found to be the strongest predictor of adherence. Interventions aimed at increasing community awareness of the AL dosing regimen, use of child friendly formulations and improving health workers' prescribing practices are likely to ensure higher adherence to AL and eventual treatment success.
Background: Operational vector sampling methods lack standardization, making quantitative compari... more Background: Operational vector sampling methods lack standardization, making quantitative comparisons of malaria transmission across different settings difficult. Human landing catch (HLC) is considered the research gold standard for measuring human-mosquito contact, but is unsuitable for large-scale sampling. This study assessed mosquito catch rates of CDC light trap (CDC-LT), Ifakara tent trap (ITT), window exit trap (WET), pot resting trap (PRT), and box resting trap (BRT) relative to HLC in western Kenya to 1) identify appropriate methods for operational sampling in this region, and 2) contribute to a larger, overarching project comparing standardized evaluations of vector trapping methods across multiple countries. Methods: Mosquitoes were collected from June to July 2009 in four districts: Rarieda, Kisumu West, Nyando, and Rachuonyo. In each district, all trapping methods were rotated 10 times through three houses in a 3 × 3 Latin Square design. Anophelines were identified by morphology and females classified as fed or non-fed. Anopheles gambiae s.l. were further identified as Anopheles gambiae s.s. or Anopheles arabiensis by PCR. Relative catch rates were estimated by negative binomial regression.
The status of resistance was investigated in Anopheles gambiae sensu lato and An. funestus (Dipte... more The status of resistance was investigated in Anopheles gambiae sensu lato and An. funestus (Diptera: Culicidae) mosquitoes from western Kenya to four classes of insecticides approved by World Health Organization for indoor residual spraying. The prevalence of the knockdown-resistance (kdr) mutation associated with resistance to pyrethroids and DDT was determined in An. gambiae s.l.. Standard World Health Organization diagnostic bioassay kits for DDT (an organochlorine), fenitrothion (an organophosphate), bendiocarb (a carbamate), and the pyrethoirds, lambdacyhalothrin and permethrin, were used. Knockdown every 10 min and mortality 24 h after exposure were noted. Controls not treated with insecticides and with the susceptible An. gambiae KISUMU strain were included in the bioassays. The presence of the kdr gene was determined using a standard diagnostic polymerase chain reaction assay. Over 98% mortality was observed for tests with all insecticides for both An. gambiae s.l. and An. funestus. Knockdown rates were not significantly different between An. gambiae s.l. and the KISUMU strain control. 50% and 95% knockdown times were either slightly lower than those for the KISUMU strain or higher by factors of less than 1.6. The mean frequency of the East African kdr mutation was 24.7% in An. gambiae sensu strictu. Based on conventional criteria where susceptibility is defined by mortality rates >98% 24 h after exposure, no evidence for resistance was found, implying that vector control measures employing any of the insecticides tested would be unhampered by resistance. The observed frequencies of the kdr mutation do not appear to compromise the effectiveness of the insecticides. The need for continuous monitoring of the status of insecticide resistance and of the impact of any observed resistance on the efficacy of vector control programs employing insecticides is apparent.
More focus is given to mosquito larval control due to the necessity to use several control techni... more 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.
We determined the nutritional status of children less than five years of age in an area in rural ... more We determined the nutritional status of children less than five years of age in an area in rural western Kenya with intense malaria transmission, a high prevalence of severe anemia and human immunodeficiency virus, and high infant and under-five mortality (176/1,000 and 259/1,000). No information is available on the prevalence of malnutrition in this area. Three cross-sectional surveys were conducted between 1996 and 1998 to monitor the effect of insecticide-treated bed nets on child morbidity. Anthropometric indices are presented for 2,103 children collected prior to and during intervention (controls only). The prevalence of stunting (Z-scores for height-for-age [HAZ] <−2), wasting (Z-scores for weight-for-height [WHZ] <−2) and being underweight (Z-scores for weight-for-age [WAZ] <−2) was 30%, 4%, and 20%, respectively. This was severe (Z-score <−3) in 12% (stunting), 1% (wasting), and 5% (underweight) of the children. Few children less than three months of age were malnourished (<2%), but height-for-age and weight-forage deficits increased rapidly in children 3−18 months of age, and were greatest in children 18−23 months old (44% stunted and 34% underweight). While the mean HAZ and WAZ stabilized from 24 months of age onwards, they still remained substantially below the reference median with no evidence of catch-up growth. Malnutrition is likely to interact with infectious diseases, placing children 3−24 months of age at high risk of premature death in this area.
Information on the impact of insecticide (permethrin)-treated bed nets (ITNs) from randomized con... more Information on the impact of insecticide (permethrin)-treated bed nets (ITNs) from randomized controlled trials in areas of intense perennial malaria transmission is limited. As part of a large-scale, community-based, group-randomized controlled trial of the effect of ITNs on childhood mortality in a holoendemic area in western Kenya, we conducted three cross-sectional surveys in 60 villages to assess the impact of ITNs on morbidity in 1,890 children less than three years old. Children in ITN and control villages were comparable pre-intervention, but after the introduction of ITNs, children in intervention villages were less likely to have recently experienced illness requiring treatment (protective efficacy [95% confidence intervals] ס 15% [1−26%]), have an enlarged spleen (32% [20−43%]), be parasitemic (19% [11−27%]), have clinical malaria (44% [6−66%]), have moderately severe anemia (hemoglobin level < 7.0 g/dL; 39% [18−54%]), or have a pruritic body rash, presumably from reduced nuisance insect bites (38% [24−50%]). Use of ITNs was also associated with significantly higher mean weight-for-age Z-scores and mid-upper arm circumferences. There was no evidence, however, that ITNs reduced the risk of helminth infections, diarrhea, or upper or lower respiratory tract infections. The ITNs substantially reduced malaria-associated morbidity and improved weight gain in young children in this area of intense perennial malaria transmission.
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Papers by John Vulule