Barriers and facilitators of integrated hepatitis B, C, and HIV screening among pregnant mothers and their newborns attending maternal and newborn clinics in Koboko District, Uganda: A qualitative inquiry of providers' perspective.

Background: HIV and HBV remain significant public health challenges characterized by high prevalence, morbidity, and mortality, especially among women of reproductive age in Uganda. However, both HIV and HBV patients are managed in separate clinics with separate staff even though they all receive ART. Patients with HBV do not receive routine counselling and education, and there are limited resources for laboratory investigation coupled with a high loss to follow-up. This study set out to "assess barriers and facilitators of integrated viral hepatitis B C and HIV care model to optimize screening uptake among mothers and newborns at health facilities in Koboko District, west Nile sub-region, Uganda". Methods: A cross-sectional grounded theory qualitative approach was employed in an institutional setting (HC IIIs). Data was audio recorded using a recording device during the key informant interviews and was transcribed after all interviews were conducted. Data was then analyzed using framework analysis. Results: The following facilitated integration: High prevalence, and therefore burden of hepatitis B infection in West Nile region, team spirit by the health workers, reduced long waiting time, availability of medical products such as HBV and HCV test kits, integration of HBV and HIV into HMIS2 form and availability of support from implementing partners such as Infectious Dease Institute which offered mentorship and training on integration and support supervision. Conclusion: Barriers to integration included; knowledge gap among health care workers, lack of transport for patients, language barriers during health education, inadequate human resources for health, stock-out of testing kits for HBV and HCV, lack of HMIS 2 column to capture HCV data, lack of funds to facilitate follow up of patients after referral for further investigation upon suspected cases of HBV and HCV. The study participants recommended; Promoting the integration of HBV, HCV, and HIV into routine health services; ensuring a constant supply of HBV, and HCV test kits to avoid stock-out; Engaging VHTs/Community health volunteers to support follow-up of patients and conducting health care workers performance reviews; addressing the issue of inadequate human resource; and finally dealing with misconceptions at community level about HBV and HCV diseases which hinder access to services.

The effects of HIV self-testing kits in increasing uptake of male partner testing among pregnant women attending antenatal clinics in Kenya: a randomized controlled trial.

INTRODUCTION: HIV self-testing could add a new approach to scaling up HIV testing with potential of being high impact, low cost, confidential, and empowering for users. METHODS: Pregnant women attending antenatal clinics (ANC) and their male partners were recruited in 14 clinics in the eastern and central regions of Kenya and randomly allocated to intervention or control arms at a ratio of 1:1:1. Arm 1 received the standard of care, which involved invitation of the male partner to the clinic through word of mouth, arm 2 received an improved invitation letter, and arm 3 received the same improved letter and, two self-testing kits. Analysis was done using adjusted odds ratios (aOR) at 95% confidence intervals (CI) to calculate and determine effects of HIV self-testing in increasing uptake of male partner testing. RESULTS: A total of 1410 women and 1033 men were recruited; 86% (1217) women and 79% (1107) couples were followed up. In arm 3, over 80% (327) of male partners took HIV test, compared to only 37% (133) in arm 2 and 28% (106) in arm one. There was a statistical significance between arm one and two (p-value=0.01) while arm three was statistically significant compared to arm two (p-value<0.001). Men in arm three were twelve times more likely to test compared to arm one (aOR 12.45 (95% CI 7.35, 21.08)). CONCLUSION: Giving ANC mothers test kits and improved male invitation letter increased the likelihood of male partner testing by twelve times. These results demonstrate that HIV self-test kits could complement routine HIV testing methods in the general population.

Social Networks and Decision Making for Clandestine Unsafe Abortions: Evidence from Kenya.

Little is known about the role of social networks in promoting clandestine abortions. This study investigated the role social networks play in decision making for and facilitation of clandestine abortions. It was a mixed method study in which 320 women treated for complications of unsafe abortions were interviewed in a cross sectional survey to determine their consultation with social networks and how this ended up in clandestine abortions. Information obtained was supplemented with information from focus group discussions, case studies and key informant interviews. It was found that 95% of women consulted their social networks as part of decision making before aborting clandestinely and unsafely. The man responsible for pregnancy, friend of same sex and woman's mother were the most consulted at 64%, 32% and 23% respectively. 92% of advice was for the woman to abort. The man responsible for pregnancy and the woman's mother were the most influential advisors (p < 0.05). Intermediaries linked the woman to clandestine and unsafe abortion and included agents and previous clients of clandestine abortion providers and the woman's friends and relatives. Decision making and seeking for clandestine abortion were therefore found to be shared responsibilities. It is recommended that programs for reducing unsafe abortions be designed with this fact in mind.

Law and pediatric HIV testing: realizing the right to health in Kenya.

Realization of the right to health occurs along a continuum including national ratification of international treaties such as the Convention on the Rights of the Child, passage of domestic laws and policies that may specify modes of implementation and enforcement such as Kenya's Constitution and HIV and AIDS Prevention and Control Act, and actual implementation of domestic laws and policies such as through the regulation and delivery of health services. The stages heuristic theoretical framework describes the public policy continuum as consisting of marked stages: agenda setting, policy formulation, policy implementation, and evaluation. This case study illustrates the continuum in Kenya with regard to pediatric HIV testing. Kenya has made progress applying law, policy, and science to reduce vertical transmission of HIV and increase HIV testing of infants, although several challenges remain. Progress in policy implementation may reduce mother-to-child transmission and increase pediatric HIV testing.

Law and pediatric HIV testing: realizing the right to health in Kenya.

Realization of the right to health occurs along a continuum including national ratification of international treaties such as the Convention on the Rights of the Child, passage of domestic laws and policies that may specify modes of implementation and enforcement such as Kenya's Constitution and HIV and AIDS Prevention and Control Act, and actual implementation of domestic laws and policies such as through the regulation and delivery of health services. The stages heuristic theoretical framework describes the public policy continuum as consisting of marked stages: agenda setting, policy formulation, policy implementation, and evaluation. This case study illustrates the continuum in Kenya with regard to pediatric HIV testing. Kenya has made progress applying law, policy, and science to reduce vertical transmission of HIV and increase HIV testing of infants, although several challenges remain. Progress in policy implementation may reduce mother-to-child transmission and increase pediatric HIV testing.

Evaluating the effects of community-based organization engagement on HIV and AIDS-related risk behavior in Kenya.

International donors have increasingly shifted AIDS funding directly to community-based organizations (CBOs) with the assumption that responding to the epidemic is best achieved at the community level. The World Bank, ICF Macro, and the National Council for Population and Development in Kenya, conducted a study to evaluate the community response in Kenya. The study used a quasi-experimental design comparing seven study communities and seven comparison communities in Nyanza Province and Western Province. We examined the impact of CBO activity on individual and community-level outcomes, including HIV knowledge, awareness and perceptions, sexual risk behavior, and social transformation (gender ideology and social capital). The study consisted of two components: a household survey conducted in all 14 communities, and qualitative data collected in a subset of communities. Individuals in communities with higher CBO engagement were significantly more likely to have reported consistent condom use. Higher CBO engagement was associated with some measures of social capital, including participation in local and national elections, and participation in electoral campaigns. CBOs provide added value in addressing the HIV and AIDS epidemic in very targeted and specific ways that are closely tied to the services they provide (e.g., prevention education); thus, increasing CBO engagement can be an effective measure in scaling up prevention efforts in those areas.

Correlates of HIV Infection Among Sexually Active Adults in Kenya: A National Population-Based Survey.

OBJECTIVE: To identify factors associated with prevalent HIV in a national HIV survey in Kenya. METHODS: The Kenya AIDS Indicator Survey was a nationally representative population-based sero-survey that examined demographic and behavioral factors and serologic testing for HIV, HSV-2 and syphilis in adults aged 15-64 years. We analyzed questionnaire and blood testing data to identify significant correlates of HIV infection among sexually active adults. RESULTS: Of 10,957 eligible women and 8,883 men, we interviewed 10,239 (93%) women and 7,731 (87%) men. We collected blood specimens from 9,049 women and 6,804 men of which 6,447 women and 5,112 men were sexually active during the 12 months prior to the survey. HIV prevalence among sexually active adults was 7.4%. Factors independently associated with HIV among women were region (Nyanza vs Nairobi: adjusted OR [AOR] 1.6, 95%CI 1.1-2.3), number of lifetime sex partners (6-9 vs 0-1 partners: AOR 3.0, 95%CI 1.6-5.9), HSV-2 (AOR 6.5, 95%CI 4.9-8.8), marital status (widowed vs never married: AOR 2.7, 95%CI 1.5-4.8) and consistent condom use with last sex partner (AOR 2.3, 95%CI 1.6-3.4). Among men, correlates of HIV infection were 30-to-39-year-old age group (AOR 5.2, 95%CI 2.6-10.5), number of lifetime sex partners (10+ vs 0-1 partners, AOR 3.5, 95%CI 1.4-9.0), HSV-2 (AOR 4.7, 95%CI 3.2-6.8), syphilis (AOR 2.4, 95%CI 1.4-4.0), consistent condom use with last sex partner (AOR 2.1, 95% CI 1.5-3.1) and lack of circumcision (AOR 4.0, 95%CI 2.8 - 5.5). CONCLUSION: Kenya's heterogeneous epidemic will require regional and gender-specific prevention approaches.

The levels of CD16/Fc gamma receptor IIIA on CD14+ CD16+ monocytes are higher in children with severe Plasmodium falciparum anemia than in children with cerebral or uncomplicated malaria.

Fc gamma receptor IIIA (CD16/Fc gamma RIIIA) on monocytes/macrophages may play an important role in the pathogenesis of severe malarial anemia (SMA) by promoting phagocytosis of IgG-coated uninfected red cells and by allowing the production of tumor necrosis factor alpha (TNF-alpha) upon cross-linking by immune complexes (ICs). However, not much is known about the differential expression of this receptor on monocytes of children with severe malaria and uncomplicated malaria. Therefore, we investigated the expression of CD16/Fc gamma RIIIA on monocytes of children with SMA, cerebral malaria (CM), and their age-matched uncomplicated malaria controls by flow cytometry. Since CD14 low (CD14(+)) monocytes are considered more mature and macrophage-like than CD14 high (CD14(++)) monocytes, we also compared the level of expression of CD16/Fc gamma RIIIA according to the CD14 level and studied the relationship between CD16/Fc gamma RIIIA expression and intracellular TNF-alpha production upon stimulation by ICs. CD16/Fc gamma RIIIA expression was the highest overall on CD14(+) CD16(+) monocytes of children with SMA at enrollment. At convalescence, SMA children were the only ones to show a significant decline in the same parameter. In contrast, there were no significant differences among groups in the expression of CD16/Fc gamma RIIIA on CD14(++) CD16(+) monocytes. A greater percentage of CD14(+) CD16(+) monocytes produced TNF-alpha upon stimulation than any other monocyte subset, and the amount of intracellular TNF-alpha correlated positively with CD16/Fc gamma RIIIA expression. Furthermore, there was an inverse correlation between hemoglobin levels and CD16/Fc gamma RIIIA expression in children with SMA and their controls. These data suggest that monocytes of children with SMA respond differently to Plasmodium falciparum infection by overexpressing CD16/Fc gamma RIIIA as they mature, which could enhance erythrophagocytosis and TNF-alpha production.

Naturally acquired hemozoin by monocytes promotes suppression of RANTES in children with malarial anemia through an IL-10-dependent mechanism.

Regulated upon activation, normal T-cell expressed, and secreted (RANTES, CCL-5) is an important immunoregulatory mediator that is suppressed in children with malarial anemia (MA). Although pro-inflammatory (e.g., TNF-alpha, IL-1beta and IFN-gamma) and anti-inflammatory (e.g., IL-4, IL-10 and IL-13) cytokines regulate RANTES production, their effect on RANTES in children with MA has not been determined. Since intraleukocytic malarial pigment, hemozoin (Hz), causes dysregulation in chemokine and cytokine production, the impact of naturally acquired Hz (pfHz) on RANTES and RANTES-regulatory cytokines (TNF-alpha, IFN-gamma, IL-1beta, IL-4, IL-10, and IL-13) was examined. Circulating RANTES levels progressively declined with increasing levels of pigment-containing monocytes (PCM) (P=0.035). Additional experiments in cultured peripheral blood mononuclear cells (PBMC) showed that monocytic acquisition of pfHz (in vivo) was associated with suppression of RANTES under baseline (P=0.001) and stimulated conditions (P=0.072). Although high PCM levels were associated with decreased circulating IFN-gamma (P=0.003) and IL-10 (P=0.010), multivariate modeling revealed that only PCM (P=0.048, beta=-0.171) and IL-10 (P<0.0001, beta=-0.476) were independently associated with RANTES production. Subsequent in vitro experiments revealed that blockade of endogenous IL-10 significantly increased RANTES production (P=0.028) in PBMC from children with naturally acquired Hz. Results here demonstrate that monocytic acquisition of Hz suppresses RANTES production in children with MA through an IL-10-dependent mechanism.

Home management of diarrhea among underfives in a rural community in Kenya: household perceptions and practices.

INTRODUCTION: Diarrheal disease is a major cause of morbidity and mortality among under-fives especially in rural and peri-urban communities in developing countries. Home management of diarrhea is one of the key household practices targeted for enhancement in the Community Integrated Management of Childhood Illness (C-IMCI) strategy. OBJECTIVE: The aim of this study was to determine the perceptions of mothers/caregivers regarding the causes of diarrhea among under-fives and how it was managed in the home before seeking help from Community Health Workers or health facilities. DESIGN: A household longitudinal study was conducted in Nyando district, Kenya in 2004-2006 adopting both qualitative and quantitative approaches. SUBJECTS: A total of 927 mothers/caregivers of under-fives participated in the study. MAIN OUTCOME MEASURES: Perceived causes of childhood diarrhoea, action taken during diarrhea, fluid intake, recognition of signs of dehydration, feeding during convalescence, adherence to treatment and advice. RESULTS: Majority of the respondents 807 (87.1%) reported that their children had suffered from diarrhea within the last 2 weeks before commencement of the study. Diarrhea was found to contribute to 48% of child mortality in the study area. Perceived causes of diarrhea were: unclean water 524 (55.6%), contaminated food 508 (54.9%), bad eye 464 (50.0%), false teeth 423 (45.6%) and breast milk 331 (35.8%). More than 70% of mothers decreased fluid intake during diarrhea episodes. The mothers perceived wheat flour, rice water and selected herbs as anti-diarrheal agents. During illness, 239 (27.8%) of the children were reported not to have drunk any fluids at all, 487 (52.5%) drunk much less and only 93 (10.0%) were reported to have drunk more than usual. A significant 831 (89.6%) withheld milk including breast milk with the notion that it enhanced diarrhea. CONCLUSION: Based on these findings, there is need to develop and implement interactive communication strategies for the health workers and mothers to address perceptions and misconceptions and facilitate positive change in the household practice on management of diarrhea among under-fives.

Combining evidence of natural selection with association analysis increases power to detect malaria-resistance variants.

Statistical power to detect disease variants can be increased by weighting candidates by their evidence of natural selection. To demonstrate that this theoretical idea works in practice, we performed an association study of 10 putative resistance variants in 471 severe malaria cases and 474 controls from the Luo in Kenya. We replicated associations at HBB (P=.0008) and CD36 (P=.03) but also showed that the same variants are unusually differentiated in frequency between the Luo and Yoruba (who historically have been exposed to malaria) and the Masai and Kikuyu (who have not been exposed). This empirically demonstrates that combining association analysis with evidence of natural selection can increase power to detect risk variants by orders of magnitude--up to P=.000018 for HBB and P=.00043 for CD36.

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.

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.

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.

Immune complex levels in children with severe Plasmodium falciparum malaria.

Malaria infection leads to the formation of circulating immune complexes. However, it is unclear whether these complexes play a role in the pathogenesis of complicated Plasmodium falciparum malaria. This study aimed at determining if there are differences in the levels of immune complexes between children with severe malaria-associated anemia and cerebral malaria and between each of these two groups and their respective uncomplicated symptomatic malaria or healthy asymptomatic controls. Children with severe malaria-associated anemia and cerebral malaria had significantly higher immune complex levels than their respective controls, but there were no significant differences in the levels between the two severe malaria groups. In addition, there was an inverse relationship between the hemoglobin levels and immune complex levels in the severe anemia controls, suggesting that immune complexes may contribute to erythrocyte destruction in these children. These results suggest that immune complex levels alone cannot account for the differences in the distinct clinical presentation between severe malaria-associated anemia and cerebral malaria.

Measurement of antibody levels against region II of the erythrocyte-binding antigen 175 of Plasmodium falciparum in an area of malaria holoendemicity in western Kenya.

Region II of the 175-kDa erythrocyte-binding antigen (EBA-175RII) of Plasmodium falciparum is functionally important in sialic acid-dependent erythrocyte invasion and is considered a prime target for an invasion-blocking vaccine. The objectives of this study were to (i) determine the prevalence of anti-EBA-175RII antibodies in a naturally exposed population, (ii) determine whether naturally acquired antibodies have a functional role by inhibiting binding of EBA-175RII to erythrocytes, and (iii) determine whether antibodies against EBA-175RII correlate with immunity to clinical malaria. We treated 301 lifelong residents of an area of malaria holoendemicity in western Kenya for malaria, monitored them during a high-transmission season, and identified 33 individuals who were asymptomatic despite parasitemia (clinically immune). We also identified 50 clinically susceptible individuals to serve as controls. These 83 individuals were treated and monitored again during the subsequent low-transmission season. Anti-EBA-175RII antibodies were present in 98.7% of the individuals studied. The antibody levels were relatively stable between the beginning and end of the high-transmission season and correlated with the plasma EBA-175RII erythrocyte-binding-inhibitory activity. There was no difference in anti-EBA-175RII levels or plasma EBA-175RII erythrocyte-binding-inhibitory activity between clinically immune and clinically susceptible groups. However, these parameters were higher in nonparasitemic than in parasitemic individuals at enrollment. These results suggest that although antibodies against EBA-175RII may be effective in suppressing some of the wild parasite strains, EBA-175RII is unlikely to be effective as a monovalent vaccine against malaria, perhaps due to allelic heterogeneity and/or presence of sialic acid-independent strains.

Short report: Evaluation of hepatic fibrosis in persons co-infected with Schistosoma mansoni and human immunodeficiency virus 1.

To investigate whether infection with human immunodeficiency virus 1 (HIV-1) affects fibrosis development in patients infected with Schistosoma mansoni, we evaluated schistosomiasis-induced pathology in the livers of Kenyan patients co-infected with HIV-1. Compared with persons with schistosomiasis alone (n = 58), there were no significant differences in distribution of ultrasound-detectable pathology in persons with HIV-1 co-infection (n = 23). Similarly, serum aspartate aminotransferase levels were not significantly different in HIV-1+ individuals. Hepatic fibrosis was associated with significantly decreased CD4+ T cell counts, even in the absence of HIV-1 infection. These data suggest that HIV-1 co-infection does not significantly alter the proportion of patients experiencing schistosomiasis-induced fibrosis, but pathology associated with S. mansoni infections leads to CD4+ T cell reductions and thereby may exacerbate the effects of HIV-1 in co-infected individuals.

Association of interferon-gamma responses to pre-erythrocytic stage vaccine candidate antigens of Plasmodium falciparum in young Kenyan children with improved hemoglobin levels: XV. Asembo Bay Cohort Project.

Previous studies in animal models have revealed an association between interferon-gamma (IFN-gamma), produced by CD8+ T cells and irradiated sporozoite-induced sterile immunity. To determine whether IFN-gamma can serve as a marker of pre-erythrocytic protective immunity in individuals naturally exposed to malaria, we characterized IFN-gamma and lymphocyte proliferative responses to previously defined CD8+ cytotoxic T lymphocyte (CTL) epitopes from six pre-erythrocytic stage antigens in 107 children six months to two years old from a community-based birth cohort in western Kenya. We found that IFN-gamma positive responders had higher hemoglobin (Hb) levels and significantly reduced prevalence of severe malarial anemia one month after the test compared with IFN-gamma non-responders, suggesting that IFN-gamma immune responses to these pre-erythrocytic antigens were associated with protection against malarial anemia. Children who responded by lymphocyte proliferation had a significantly longer time to first documented malaria parasitemia after birth; however, there was no correlation between the presence of lymphocyte proliferative response and higher Hb levels. We propose that IFN-gamma production could be used as a potential marker of protective immunity against malaria associated anemia in young children living in malaria holoendemic areas.

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.

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. Our results suggest that the use of ITNs decreases antibody responses to LSA-1 and MSP-1 antigens in pregnant women with associated reductions in levels of the same antibodies in cord blood. In contrast, ITN use was found to be associated with increased antibody responses to CSP in pregnant women, but had no effect on antibody levels to CSP in cord blood.