Letter to the editors.
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Bedding and Linens↗
Biomedical subjects
John E Gimnig
Publications and source records attributed to John E Gimnig.
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.
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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.
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Severe cutaneous reactions to sulfadoxine-pyrimethamine and trimethoprim-sulfamethoxazole in Blantyre District, Malawi.
We estimated the frequency of clinically diagnosed Stevens-Johnson syndrome and toxic epidermal necrolysis associated with sulfadoxine-pyrimethamine (SP) and trimethoprim-sulfamethoxazole (CTX) in Blantyre District, Malawi. Cases were detected by passive surveillance at 22 health centers from March 2001 through September 2002. Denominators were estimated from the Malawi national census for Blantyre District and the frequency of SP and CTX use reported in five household surveys. Crude rates of adverse reactions were estimated to be 1.2 per 100,000 exposures for SP and 1.5 per 100,000 exposures for CTX. Rates were higher in adults (1.7 cases per 100,000 SP exposures and 2.6 cases per 100,000 CTX exposures) and in persons positive for human immunodeficiency virus (4.9 cases per 100,000 SP exposures and 8.4 cases per 100,000 CTX exposures). Infrequent treatment doses with SP are associated with a low risk of an adverse cutaneous reaction, and SP can be recommended for treatment of malaria in areas where P. falciparum is susceptible.
Adolescent↗
Larval development of the molecular forms of Anopheles gambiae (Diptera: Culicidae) in different habitats: a transplantation experiment.
We compared the development of the molecular forms of Anopheles gambiae s.s. in different larval habitats. First stage larvae (L1s) of wild-caught females were placed into cages in natural habitats of the M form (rice fields) or the S form (puddles/ quarries). Each cage was covered with cloth, allowing exchange of water, solutes, and small particles, including microorganisms, and was seeded with 100 L1s of a single form (M or S) or by a mixture of 50:50 of M and S forms. Emergence success of both forms in puddles and quarries was three-fold higher than in the rice fields. The emergence rate of the S form was higher than that of the M form in both habitats, but the form x habitat interaction was not significant. In temporary larval sites such as puddles, emergence success of the M form was lower in mixed cages than in single form cages, whereas the reverse was true for the S form, suggesting competition between the forms. The median developmental time was not significantly different between forms. Although these findings demonstrate differences between forms, they do not suggest that their spatial segregation is determined by differences in their exploitation of the physical and chemical conditions in these environments. These results should be regarded with caution because small numbers of first stage larvae could pass through the cloth of the cages.
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Laboratory wash resistance of long-lasting insecticidal nets.
Long-lasting insecticidal nets (LLINs) may eliminate the need for retreatment of mosquito nets used for the control of malaria and other vector-borne diseases. The efficacy of LLINs after repeated washing under laboratory conditions has been used to predict long-lasting efficacy under field conditions. We evaluated under laboratory conditions the wash resistance of two LLINs (PermaNet 1.0, Vestergaard-Frandsen, Denmark; Olyset, Sumitomo Chemical Co., Japan), two candidate LLINs (Dawa, Siamdutch Mosquito Netting Co., Thailand; Insector, Athanor, France) and a net treated with a process designed to increase its wash resistance and compared them with conventionally treated nets (deltamethrin, 25 mg/m(2)). Nets of all six types were washed using a standard protocol and tested weekly using WHO cone bioassays with Anopheles gambiae (Kisumu strain). The PermaNet 1.0 was the most wash resistant with >50% mosquito mortality in WHO cone bioassays after as many as 20 washes. The Dawa net also retained some activity after repeated washing but exhibited wide variation in insecticide retention and biological activity. The remaining nets lost >90% of their biological activity after six washes as measured by 24-h mortality of A. gambiae in WHO cone tests. After 20 washes, all nets lost >50% of their initial insecticide concentrations except for the Olyset net. After 20 washes, nets were heated for 4 h at 60 degrees C to determine whether biological activity could be restored by heat-assisted regeneration. Only the Olyset net was regenerated by heating, with average mosquito mortality and knockdown in WHO cone tests rising to >90% after heating for 4 h at 60 degrees C. However, regeneration of the biological activity of Olyset nets that had been washed three times did not occur at 30 degrees C or 35 degrees C after 12 weeks. The wash resistance of these LLINs corresponded well to their retention of biological activity observed in a field trial, suggesting that wash resistance may be a good predictor of the longevity of insecticidal activity of LLINs under field conditions.
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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.
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Sustainability of reductions in malaria transmission and infant mortality in western Kenya with use of insecticide-treated bednets: 4 to 6 years of follow-up.
CONTEXT: Insecticide-treated bednets reduce malaria transmission and child morbidity and mortality in short-term trials, but this impact may not be sustainable. Previous investigators have suggested that bednet use might paradoxically increase mortality in older children through delayed acquisition of immunity to malaria. OBJECTIVES: To determine whether adherence to and public health benefits of insecticide-treated bednets can be sustained over time and whether bednet use during infancy increases all-cause mortality rates in older children in an area of intense perennial malaria transmission. DESIGN AND SETTING: A community randomized controlled trial in western Kenya (phase 1: January 1997 to February 2000) followed by continued surveillance of adherence, entomologic parameters, morbidity indicators, and all-cause mortality (phase 2: April 1999 to February 2002), and extended demographic monitoring (January to December 2002). PARTICIPANTS: A total of 130,000 residents of 221 villages in Asembo and Gem were randomized to receive insecticide-treated bednets at the start of phase 1 (111 villages) or phase 2 (110 villages). MAIN OUTCOME MEASURES: Proportion of children younger than 5 years using insecticide-treated bednets, mean number of Anopheles mosquitoes per house, and all-cause mortality rates. RESULTS: Adherence to bednet use in children younger than 5 years increased from 65.9% in phase 1 to 82.5% in phase 2 (P<.001). After 3 to 4 years of bednet use, the mean number of Anopheles mosquitoes per house in the study area was 77% lower than in a neighboring area without bednets (risk ratio, 0.23; 95% confidence interval [CI], 0.15-0.35). All-cause mortality rates in infants aged 1 to 11 months were significantly reduced in intervention villages during phase 1 (hazard ratio [HR], 0.78; 95% CI, 0.67-0.90); low rates were maintained during phase 2. Mortality rates did not differ during 2002 (after up to 6 years of bednet use) between children from former intervention and former control households born during phase 1 (HR, 1.01; 95% CI, 0.86-1.19). CONCLUSIONS: The public health benefits of insecticide-treated bednets were sustained for up to 6 years. There is no evidence that bednet use from birth increases all-cause mortality in older children in an area of intense perennial transmission of malaria.
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Spatial and temporal variation in kinship among Anopheles gambiae (Diptera: Culicidae) mosquitoes.
Genetic relatedness (kinship) among Anopheles gambiae Giles female mosquitoes was assessed using microsatellite loci in five locations across Africa and in nine samples taken between 1994 and 1999 in western Kenya. We assessed variation among samples in kinship as well as the effect of distance on kinship. Relatedness within populations was low, and differences among samples taken at various times from one locale and from different locales were minimal. Mosquitoes collected from the same compound were slightly more closely related than those collected from different compounds. Our results suggest that newly emerged female siblings move relatively short distances into a few nearby compounds for blood feeding, but that they lay eggs in a more distant location. Kinship decreased nonlinearly with increasing distance. The strongest relationship between kinship and distance was observed for mosquitoes collected 0-3 km apart (-0.014/km, P < 0.001). The effect of distance decreased with increasing distance between mosquitoes; at 7 km or more, the kinship/distance slope approached zero and the intercept became negative, suggesting that beyond this range kinship does not decline with distance. This distance may thus represent the upper limit of the diameter of the basic reproductive unit. Nevertheless, the effect of distance on kinship is weak, reflecting extensive dispersal. Because females mate within days after emergence from larval habitats, where the likelihood of mating with a sibling is presumably highest, we propose a slight inbreeding effect.
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The efficacy of permethrin-treated bed nets on child mortality and morbidity in western Kenya I. Development of infrastructure and description of study site.
Randomized controlled trials in sub-Saharan Africa have shown that permethrin-treated bed nets and curtains reduce all-cause child mortality by 15-33% in areas with low or high but seasonal malaria transmission. This report describes the study site for a community-based, group-randomized, controlled trial in an area of high and year-round malaria transmission in western Kenya. We outline the development of the human and physical infrastructure required to conduct this trial and discuss some of the difficulties encountered and lessons learned in conducting it.
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The efficacy of permethrin-treated bed nets on child mortality and morbidity in western Kenya II. Study design and methods.
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.
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Impact of permethrin-treated bed nets on entomologic indices in an area of intense year-round malaria transmission.
The effect of permethrin-treated bed nets (ITNs) on malaria vectors was studied as part of a large-scale, randomized, controlled trial in western Kenya. Indoor resting densities of fed Anopheles gambiae s.l. and An. funestus in intervention houses were 58.5% (P = 0.010) and 94.5% (P = 0.001) lower, respectively, compared with control houses. The sporozoite infection rate in An. gambiae s.l. was 0.8% in intervention areas compared with 3.4% (P = 0.026) in control areas, while the sporozoite infection rates in An. funestus were not significantly different between the two areas. We estimated the overall transmission of Plasmodium falciparum in intervention areas to be 90% lower than in control areas. Permethrin resistance was not detected during the study period. As measured by densities of An. gambiae s.l., the efficacy of bed nets decreased if one or more residents did not sleep under a net or if bed nets had not been re-treated within six months. These results indicate that ITNs are optimally effective if used every night and if permethrin is reapplied at least biannually.
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Efficacy of permethrin-treated bed nets in the prevention of mortality in young children in an area of high perennial malaria transmission in western Kenya.
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 Asembo (1997-1998) and in Gem (1998-1999). Overall, 1,722 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 = 23% (11-34%) and 31.1 versus 28.7, PE = 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.
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Comparison of government statistics and demographic surveillance to monitor mortality in children less than five years old in rural western Kenya.
Estimates of mortality in children less than five years old using government civil registration statistics (passive surveillance) were compared against statistics generated by active demographic surveillance during a randomized controlled trial of permethrin-treated bed nets (ITNs) in western Kenya. Mortality rates were two-fold lower when estimated through civil registration compared with active prospective surveillance (rate ratio [RR] = 0.51, 95% confidence interval [CI] = 0.44-0.59). While civil registration underestimated deaths, particularly in the neonatal period, the age distribution of deaths in children 1-59 months of age was the same as with active surveillance. Seasonal mortality trends were also similar. There was no agreement between cause of death recorded by active and passive surveillance. Verbal autopsy estimated that half of all deaths were associated with malaria and pneumonia, but civil registration markedly under-reported these illnesses; incidence RR (95% CI) = 0.18 (0.14-0.24), and 0.05 (0.03-0.08), respectively, while over-reporting deaths due to measles (RR = 15.5 [95% CI = 7.3-33.2]). Government statistics under-represent mortality, particularly neonatal mortality, in children less than five years of age in rural areas of Kenya. They can provide accurate information on the age-distribution of deaths among children 1-59 months old, and on seasonal trends, but not on disease-specific mortality.
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Impact of permethrin-treated bed nets on the incidence of sick child visits to peripheral health facilities.
During a randomized controlled trial of insecticide (permethrin)-treated bed nets (ITNs) in an area with intense malaria transmission in western Kenya, we monitored 20,915 sick child visits (SCVs) by children less than five years of age visiting seven peripheral health facilities. The SCVs were monitored over a four-year period both before (1995-1996) and during the intervention (1997-1998). Results are used to estimate the effect of ITNs on the burden of malaria in this community and to evaluate the potential role of these facilities in assessment of the impact of large-scale public health interventions. Compared with baseline, a 27% greater reduction in the incidence of SCVs was seen in ITN villages than in control villages (37% versus 10%; P = 0.049). A similar reduction was observed in SCVs diagnosed as malaria (35% reduction in ITN villages versus 5% reduction in controls; P = 0.04). Two-hundred sixteen SCVs per 1,000 child-years were prevented; three-fourths of these were in children less than 24 months old. As a consequence of lack of laboratory facilities, severe anemia was rarely (< 2%) diagnosed, regardless of intervention status. No effect of ITNs on the incidence of respiratory tract infections, diarrhea, and other commonly diagnosed childhood illnesses was observed. The ITNs reduced the number of SCVs due to malaria, but had no effect on other illnesses. Routine statistics from these facilities provided useful information on trends in malaria incidence, but underestimated the burden of severe anemia.
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Effect of permethrin-treated bed nets on the spatial distribution of malaria vectors in western Kenya.
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 = 0.027) and after (P = 0.002) introduction of ITNs, but this trend was significantly stronger after ITNs were introduced (P = 0.05). For An. funestus, no pre-intervention trend was observed (P = 0.373), but after the intervention, a trend of decreased abundance with closer proximity to intervention compounds developed (P = 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.
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Community-wide effects of permethrin-treated bed nets on child mortality and malaria morbidity in western Kenya.
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.
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Factors affecting use of permethrin-treated bed nets during a randomized controlled trial in western Kenya.
Adherence with permethrin-treated bed net (ITN) use and their proper deployment was directly observed in 2,178 individuals (784 households) participating in a large-scale trial of ITNs on child mortality in western Kenya. The ITNs were distributed free of charge to ensure high coverage, resulting in a ratio of 1.46 persons per ITN. Approximately 30% of ITNs present were unused. The overall percentage adherence was 72.3%. The probability of adherence by individuals depended strongly on age (relative risk [RR] = 0.86, 95% confidence limit [CL] = 0.78-0.94), in which children less than five years of age were less likely to use ITNs than older individuals, and temperature, in which ITNs were more likely to be used in periods of cooler weather. A marginally significant diminution in adherence during the second year of the project was also observed (RR = 0.83, 95% CL = 0.68-1.01). Mosquito numbers, relative wealth, number of house occupants, and the educational level of the head of the household had no effect on adherence. In unstructured questioning of house residents, excessive heat was often cited as a reason for not deploying the child's ITN. The most important reason for non-adherence was disruption of sleeping arrangements, indicating that ITNs were not readily redeployed in the face of shifting sleeping patterns due to visitors, funerals, house construction, and other events. Challenges faced by health education programs to maximize adherence with ITN use are discussed.
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