Four different study designs to evaluate vaccine safety were equally validated with contrasting limitations.

Objective: We conducted a simulation study to empirically compare four study designs [cohort, case-control, risk-interval, self-controlled case series (SCCS)] used to assess vaccine safety.

Study Design And Methods: Using Vaccine Safety Datalink data (a Centers for Disease Control and Prevention-funded project), we simulated 250 case sets of an acute illness within a cohort of vaccinated and unvaccinated children. We constructed the other three study designs from the cohort at three different incident rate ratios (IRRs, 2.

Maternal malaria and perinatal HIV transmission, western Kenya.

To determine whether maternal placental malaria is associated with an increased risk for perinatal mother-to-child HIV transmission (MTCT), we studied HIV-positive women in western Kenya. We enrolled 512 mother-infant pairs; 128 (25.0%) women had placental malaria, and 102 (19.

Sulfadoxine-pyrimethamine in treatment of malaria in Western Kenya: increasing resistance and underdosing.

Between 1993 and 1999, we monitored the efficacy of sulfadoxine-pyrimethamine in 1175 children aged <24 months receiving 2789 treatments for falciparum malaria in western Kenya using a widely deployed age-based dose regimen: infants, 125 plus 6.25 mg (sulfadoxine plus pyrimethamine); children aged 12 to 23 months; 250 plus 12.5 mg.

The effects of varying exposure to malaria transmission on development of antimalarial antibody responses in preschool children. XVI. Asembo Bay Cohort Project.

In areas of intense malaria transmission, malaria morbidity and mortality is highest in children 3-18 months old. Interventions that reduce malaria exposure early in life reduce morbidity but may also delay development of clinical immunity. We assessed the relationship between intensity of malaria exposure and development of antibody responses.

Implications of the western Kenya permethrin-treated bed net study for policy, program implementation, and future research.

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 household-level economics of using permethrin-treated bed nets to prevent malaria in children less than five years of age.

We measured the two-week household-level economic impact of insecticide (permethrin)-treated bed nets (ITNs) used to prevent malaria among children less than five years of age in Asembo, Kenya. The ITNs induced a two-week reduction of 15 Kenyan shillings (KSH) (0.25 U.

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.

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.

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.

Effects of permethrin-treated bed nets on immunity to malaria in western Kenya II. Antibody responses in young children in an area of intense malaria transmission.

As part of a large community-based trial on the impact of insecticide (permethrin)-treated bed nets (ITNs) on childhood morbidity and mortality in an area of intense perennial malaria transmission in western Kenya, we assessed the effects of ITNs on malaria-specific humoral responses in young children. The IgG responses to Plasmodium falciparum pre-erythrocytic antigens circumsporozoite protein (CSP) and liver stage antigen-1 (LSA-1) and the blood stage antigen merozoite surface protein-1 (MSP-1(19) kD) in children less than three years old were investigated during a series of cross-sectional surveys. At 14 and 22 months after the introduction of ITNs, the frequencies and levels of IgG to CSP and LSA-1 were significantly lower in children from ITN villages than in children from control villages (P < 0.

Impact of permethrin-treated bed nets on malaria and all-cause morbidity in young children in an area of intense perennial malaria transmission in western Kenya: cross-sectional survey.

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] = 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.

Impact of permethrin-treated bed nets on growth, nutritional status, and body composition of primary school children in western Kenya.

Insecticide-treated bed nets (ITNs) have been demonstrated to reduce morbidity and mortality in children less than five years of age. They have also been shown to improve the nutritional status of these children, but little is known about their impact on the nutritional status of school-age children. We evaluated the impact of ITNs on growth, nutritional status, and body composition of primary schoolchildren less than 13 years of age living in an area of intense perennial malaria transmission in western Kenya.

Impact of permethrin-treated bed nets on malaria, anemia, and growth in infants in an area of intense perennial malaria transmission in western Kenya.

As part of a community-based, group-randomized, controlled trial of insecticide-treated bed nets (ITNs) in an area with intense malaria transmission in western Kenya, a birth cohort (n = 833) was followed monthly until the age of 24 months to determine the potential beneficial and adverse effects of reduced malaria exposure during pregnancy and infancy. Malaria transmission and morbidity were comparable pre-intervention. The ITNs reduced malaria attack rates (force of infection) in infancy by 74%, and delayed the median time-to-first parasitemia (4.

Effects of permethrin-treated bed nets on immunity to malaria in western Kenya I. Antibody responses in pregnant women and cord blood in an area of intense malaria transmission.

As part of a community-based group-randomized trial on the impact of permethrin-treated bed nets (ITNs) on malaria in pregnancy in a holoendemic area of western Kenya, we assessed their effects on antibody responses to Plasmodium falciparum pre-erythrocytic antigens (recombinant circumsporozoite protein [CSP] and peptides complimentary to the repeat region of the liver stage antigen-1 [LSA-1]) and blood stage antigen (recombinant C-terminal domain of the merozoite surface protein-1 [MSP-1(19) kD]) in paired maternal/cord plasma samples obtained from 296 deliveries (157 from ITN villages and 139 control villages). Levels of total IgG and IgG subclasses 1-3 to LSA-1 and total IgG and IgG3 to MSP-1 were lower, whereas those of total IgG to CSP were significantly higher in women from ITN villages than those from control villages. In cord plasma, levels of total IgG and IgG2 to LSA-1 and IgG3 to MSP-1 were lower in ITN villages than in control villages, but antibody responses to CSP were similar.

Reduction of malaria during pregnancy by permethrin-treated bed nets in an area of intense perennial malaria transmission in western Kenya.

The impact of insecticide (permethrin)-treated bed nets (ITNs) on malaria in pregnancy was studied in a rural area in western Kenya with intense perennial malaria transmission. All households in 40 of 79 villages were randomized to receive ITNs by January 1997. The ITNs were distributed in control villages two years later.

Diagnostic and prescribing practices in peripheral health facilities in rural western Kenya.

Health facility ledgers of 11 rural health facilities in western Kenya were reviewed to evaluate diagnostic and prescribing practices. Clinics lacked laboratory facilities. Of 14,267 sick child visits (SCVs), 76% were diagnosed with malaria and/or upper respiratory infections.

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.

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.

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.

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.

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.

The effect of dual infection with HIV and malaria on pregnancy outcome in western Kenya.

Objective: To determine the effect of dual infection with HIV and malaria on birth outcomes and maternal anaemia among women delivering at a large public hospital in Kisumu, western Kenya.

Subjects And Methods: Data on obstetric and neonatal characteristics, maternal and placental parasitaemia, and postpartum haemoglobin levels were collected from women enrolled in a cohort study of the interaction between malaria and HIV during pregnancy.

Results: Between 1996 and 1999, data were available from 2466 singleton deliveries.

Treatment history and treatment dose are important determinants of sulfadoxine-pyrimethamine efficacy in children with uncomplicated malaria in Western Kenya.

This study retrospectively studied amendable determinants of sulfadoxine-pyrimethamine (SP) efficacy involving 2869 treatments among 1072 Kenyan children <5 years old who had uncomplicated malaria. The dose was based on age: one-quarter tablet was given to infants <1 year old, one-half tablet was given to 1-3-year-old children, and a full tablet was given to 4-year-old children. Only 23.

Increased efficacy of sulfadoxine-pyrimethamine in the treatment of uncomplicated falciparum malaria among children with sickle cell trait in Western Kenya.

The role of the sickle cell hemoglobin type as a determinant of treatment outcome with sulfadoxine-pyrimethamine was retrospectively studied in young children with uncomplicated falciparum malaria who lived in an area with intense perennial malaria transmission. Between 1993 and 1997, 2795 treatments involving 813 children were monitored. Sickle cell trait (HbAS) was present in 17.