Malaria, malnutrition, and birthweight: A meta-analysis using individual participant data.

BACKGROUND: Four studies previously indicated that the effect of malaria infection during pregnancy on the risk of low birthweight (LBW; <2,500 g) may depend upon maternal nutritional status. We investigated this dependence further using a large, diverse study population. METHODS AND FINDINGS: We evaluated the interaction between maternal malaria infection and maternal anthropometric status on the risk of LBW using pooled data from 14,633 pregnancies from 13 studies (6 cohort studies and 7 randomized controlled trials) conducted in Africa and the Western Pacific from 1996-2015. Studies were identified by the Maternal Malaria and Malnutrition (M3) initiative using a convenience sampling approach and were eligible for pooling given adequate ethical approval and availability of essential variables. Study-specific adjusted effect estimates were calculated using inverse probability of treatment-weighted linear and log-binomial regression models and pooled using a random-effects model. The adjusted risk of delivering a baby with LBW was 8.8% among women with malaria infection at antenatal enrollment compared to 7.7% among uninfected women (adjusted risk ratio [aRR] 1.14 [95% confidence interval (CI): 0.91, 1.42]; N = 13,613), 10.5% among women with malaria infection at delivery compared to 7.9% among uninfected women (aRR 1.32 [95% CI: 1.08, 1.62]; N = 11,826), and 15.3% among women with low mid-upper arm circumference (MUAC <23 cm) at enrollment compared to 9.5% among women with MUAC ≥ 23 cm (aRR 1.60 [95% CI: 1.36, 1.87]; N = 9,008). The risk of delivering a baby with LBW was 17.8% among women with both malaria infection and low MUAC at enrollment compared to 8.4% among uninfected women with MUAC ≥ 23 cm (joint aRR 2.13 [95% CI: 1.21, 3.73]; N = 8,152). There was no evidence of synergism (i.e., excess risk due to interaction) between malaria infection and MUAC on the multiplicative (p = 0.5) or additive scale (p = 0.9). Results were similar using body mass index (BMI) as an anthropometric indicator of nutritional status. Meta-regression results indicated that there may be multiplicative interaction between malaria infection at enrollment and low MUAC within studies conducted in Africa; however, this finding was not consistent on the additive scale, when accounting for multiple comparisons, or when using other definitions of malaria and malnutrition. The major limitations of the study included availability of only 2 cross-sectional measurements of malaria and the limited availability of ultrasound-based pregnancy dating to assess impacts on preterm birth and fetal growth in all studies. CONCLUSIONS: Pregnant women with malnutrition and malaria infection are at increased risk of LBW compared to women with only 1 risk factor or none, but malaria and malnutrition do not act synergistically.

Fetal sex and risk of pregnancy-associated malaria in Plasmodium falciparum-endemic regions: a meta-analysis.

In areas of moderate to intense Plasmodium falciparum transmission, malaria in pregnancy remains a significant cause of low birth weight, stillbirth, and severe anaemia. Previously, fetal sex has been identified to modify the risks of maternal asthma, pre-eclampsia, and gestational diabetes. One study demonstrated increased risk of placental malaria in women carrying a female fetus. We investigated the association between fetal sex and malaria in pregnancy in 11 pregnancy studies conducted in sub-Saharan African countries and Papua New Guinea through meta-analysis using log binomial regression fitted to a random-effects model. Malaria infection during pregnancy and delivery was assessed using light microscopy, polymerase chain reaction, and histology. Five studies were observational studies and six were randomised controlled trials. Studies varied in terms of gravidity, gestational age at antenatal enrolment and bed net use. Presence of a female fetus was associated with malaria infection at enrolment by light microscopy (risk ratio 1.14 [95% confidence interval 1.04, 1.24]; P = 0.003; n = 11,729). Fetal sex did not associate with malaria infection when other time points or diagnostic methods were used. There is limited evidence that fetal sex influences the risk of malaria infection in pregnancy.

Temporal trends of sulphadoxine-pyrimethamine (SP) drug-resistance molecular markers in Plasmodium falciparum parasites from pregnant women in western Kenya.

BACKGROUND: Resistance to sulphadoxine-pyrimethamine (SP) in Plasmodium falciparum parasites is associated with mutations in the dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) genes and has spread worldwide. SP remains the recommended drug for intermittent preventive treatment for malaria in pregnancy (IPTp) and information on population prevalence of the SP resistance molecular markers in pregnant women is limited. METHODS: Temporal trends of SP resistance molecular markers were investigated in 489 parasite samples collected from pregnant women at delivery from three different observational studies between 1996 and 2009 in Kenya, where SP was adopted for both IPTp and case treatment policies in 1998. Using real-time polymerase chain reaction, pyrosequencing and direct sequencing, 10 single-nucleotide polymorphisms (SNPs) of SP resistance molecular markers were assayed. RESULTS: The prevalence of quintuple mutant (dhfr N51I/C59R/S108N and dhps A437G/K540E combined genotype) increased from 7% in the first study (1996-2000) to 88% in the third study (2008-2009). When further stratified by sample collection year and adoption of IPTp policy, the prevalence of the quintuple mutant increased from 2.4% in 1998 to 44.4% three years after IPTp policy adoption, seemingly in parallel with the increase in percentage of SP use in pregnancy. However, in the 1996-2000 study, more mutations in the combined dhfr/dhps genotype were associated with SP use during pregnancy only in univariable analysis and no associations were detected in the 2002-2008 and 2008-2009 studies. In addition, in the 2008-2009 study, 5.3% of the parasite samples carried the dhps triple mutant (A437G/K540E/A581G). There were no differences in the prevalence of SP mutant genotypes between the parasite samples from HIV + and HIV- women over time and between paired peripheral and placental samples. CONCLUSIONS: There was a significant increase in dhfr/dhps quintuple mutant and the emergence of new genotype containing dhps 581 in the parasites from pregnant women in western Kenya over 13 years. IPTp adoption and SP use in pregnancy only played a minor role in the increased drug-resistant parasites in the pregnant women over time. Most likely, other major factors, such as the high prevalence of resistant parasites selected by the use of SP for case management in large non-pregnant population, might have contributed to the temporally increased prevalence of SP resistant parasites in pregnant women. Further investigations are needed to determine the linkage between SP drug resistance markers and efficacy of IPTp-SP.

Geographical distribution of schistosomiasis and soil-transmitted helminths among school children in informal settlements in Kisumu City, Western Kenya.

This cross-sectional study determined the prevalence and distribution of schistosome and soil-transmitted helminth (STH) infections among 1,308 children aged 10-18 years in 34 primary schools in 8 informal urban settlements in Kisumu City, western Kenya. Stool samples were collected and examined for eggs of Schistosoma mansoni and STH (Hookworms, Ascaris lumbricoides and Trichuris trichiura) using the Kato-Katz technique. Haematuria was used as a proxy indicator of urinary schistosomiasis. Schools and water bodies were mapped using a geographical information system. Overall, 34% of children were infected with one or more helminth species whereas 16·2% of children were infected with one or more STH species. Schools in closest proximity to Lake Victoria and River Nyamasaria had the highest S. mansoni prevalence while schools with STH were more homogenously distributed. Mean school prevalence of S. mansoni infection was 21% (range=0-69·7%), S. haematobium 3·6% (range=0-12%), hookworms 6·1% (range=0-20%), A. lumbricoides 4·9% (range=0-18·4%), and T. trichiura 7·7% (range=0-18·6%). Helminth-related morbidities were not associated with infection. Our study demonstrates that schistosomiasis and STH are important health priorities among schools in informal settlements of Kisumu City, and highlights the need for routine deworming in similar settings.

Care seeking and attitudes towards treatment compliance by newly enrolled tuberculosis patients in the district treatment programme in rural western Kenya: a qualitative study.

BACKGROUND: The two issues mostly affecting the success of tuberculosis (TB) control programmes are delay in presentation and non-adherence to treatment. It is important to understand the factors that contribute to these issues, particularly in resource limited settings, where rates of tuberculosis are high. The objective of this study is to assess health-seeking behaviour and health care experiences among persons with pulmonary tuberculosis, and identify the reasons patients might not complete their treatment. METHODS: We performed qualitative one-on-one in-depth interviews with pulmonary tuberculosis patients in nine health facilities in rural western Kenya. Thirty-one patients, 18 women and 13 men, participated in the study. All reside in an area of western Kenya with a Health and Demographic Surveillance System (HDSS). They had attended treatment for up to 4 weeks on scheduled TB clinic days in September and October 2005.The nine sites all provide diagnostic and treatment services. Eight of the facilities were public (3 hospitals and 5 health centres) and one was a mission health centre. RESULTS: Most patients initially self-treated with herbal remedies or drugs purchased from kiosks or pharmacies before seeking professional care. The reported time from initial symptoms to TB diagnosis ranged from 3 weeks to 9 years. Misinterpretation of early symptoms and financial constraints were the most common reasons reported for the delay.We also explored potential reasons that patients might discontinue their treatment before completing it. Reasons included being unaware of the duration of TB treatment, stopping treatment once symptoms subsided, and lack of family support. CONCLUSIONS: This qualitative study highlighted important challenges to TB control in rural western Kenya, and provided useful information that was further validated in a quantitative study in the same area.

Antenatal and delivery care in rural western Kenya: the effect of training health care workers to provide "focused antenatal care".

BACKGROUND: Maternal mortality remains high in developing countries and data to monitor indicators of progress in maternal care is needed. We examined the status of maternal care before and after health care worker (HCW) training in WHO recommended Focused Antenatal Care. METHODS: An initial cross-sectional survey was conducted in 2002 in Asembo and Gem in western Kenya among a representative sample of women with a recent birth. HCW training was performed in 2003 in Asembo, and a repeat survey was conducted in 2005 in both areas. RESULTS: Antenatal clinic (ANC) attendance was similar in both areas (86%) in 2005 and not significantly different from 2002 (90%). There was no difference in place of delivery between the areas or over time. However, in 2005, more women in Asembo were delivered by a skilled assistant compared to Gem (30% vs.23%, P = 0.04), and this proportion increased compared to 2002 (17.6% and 16.1%, respectively). Provision of iron (82.4%), folic acid (72.0%), sulfadoxine-pyrimethamine (61.7%), and anthelminths (12.7%) had increased in Asembo compared to 2002 (2002: 53.3%, 52.8%, 20.3%, and 4.6%, respectively), and was significantly higher than in Gem in 2005 (Gem 2005: 69.7%, 47.8%, 19.8%, and 4.1%, respectively) (P < 0.05 for all). Offering of tests for sexually transmitted diseases and providing information related to maternal health was overall low (<20%) and did not differ by area. In 2005, more women rated the quality of the antenatal service in Asembo as very satisfactory compared to Gem (17% vs. 6.5%, P < 0.05). CONCLUSIONS: We observed improvements in some ANC services in the area where HCWs were trained. However, since our evaluation was carried out 2 years after three-day training, we consider any significant, sustained improvement to be remarkable.

Reproductive health issues in rural Western Kenya.

BACKGROUND: We describe reproductive health issues among pregnant women in a rural area of Kenya with a high coverage of insecticide treated nets (ITNs) and high prevalence of HIV (15%). METHODS: We conducted a community-based cross-sectional survey among rural pregnant women in western Kenya. A medical, obstetric and reproductive history was obtained. Blood was obtained for a malaria smear and haemoglobin level, and stool was examined for geohelminths. Height and weight were measured. RESULTS: Of 673 participants, 87% were multigravidae and 50% were in their third trimester; 41% had started antenatal clinic visits at the time of interview and 69% reported ITN-use. Malaria parasitemia and anaemia (haemoglobin < 11 g/dl) were detected among 36% and 53% of the women, respectively. Geohelminth infections were detected among 76% of the 390 women who gave a stool sample. Twenty percent of women were underweight, and sixteen percent reported symptoms of herpes zoster or oral thrush in the last two months. Nineteen percent of all women reported using a contraceptive method to delay or prevent pregnancy before the current pregnancy (injection 10%, pill 8%, condom 0.4%). Twenty-three percent of multigravidae conceived their current pregnancy within a year of the previous pregnancy. More than half of the multigravidae (55%) had ever lost a live born child and 21% had lost their last singleton live born child at the time of interview. CONCLUSION: In this rural area with a high HIV prevalence, the reported use of condoms before pregnancy was extremely low. Pregnancy health was not optimal with a high prevalence of malaria, geohelminth infections, anaemia and underweight. Chances of losing a child after birth were high. Multiple interventions are needed to improve reproductive health in this area.

Association of maternal KIR gene content polymorphisms with reduction in perinatal transmission of HIV-1.

The role of killer cell immunoglobulin-like receptors (KIRs) in the transmission of HIV-1 has not been extensively studied. Here, we investigated the association of KIR gene content polymorphisms with perinatal HIV-1 transmission. The KIR gene family comprising 16 genes was genotyped in 313 HIV-1 positive Kenyan mothers paired with their infants. Gene content polymorphisms were presented as presence of individual KIR genes, haplotypes, genotypes and KIR gene concordance. The genetic data were analyzed for associations with perinatal transmission of HIV. There was no association of infant KIR genes with perinatal HIV-1 transmission. After adjustment for gravidity, viral load, and CD4 cell count, there was evidence of an association between reduction in perinatal HIV-1 transmission and the maternal individual KIR genes KIR2DL2 (adjusted OR = 0.50; 95% CI: 0.24-1.02, P = 0.06), KIR2DL5 (adjusted OR = 0.47; 95% CI: 0.23-0.95, P = 0.04) and KIR2DS5 (adjusted OR = 0.39; 95% CI: 0.18-0.80, P = 0.01). Furthermore, these maternal KIR genes were only significantly associated with reduction in perinatal HIV transmission in women with CD4 cell count ≥ 350 cells/ µl and viral load <10000 copies/ml. Concordance analysis showed that when both mother and child had KIR2DS2, there was less likelihood of perinatal HIV-1 transmission (adjusted OR = 0.44; 95% CI: 0.20-0.96, P = 0.039). In conclusion, the maternal KIR genes KIR2DL2, KIR2DL5, KIR2DS5, and KIR2DS2 were associated with reduction of HIV-1 transmission from mother to child. Furthermore, maternal immune status is an important factor in the association of KIR with perinatal HIV transmission.

HIV impairs opsonic phagocytic clearance of pregnancy-associated malaria parasites.

BACKGROUND: Primigravid (PG) women are at risk for pregnancy-associated malaria (PAM). Multigravid (MG) women acquire protection against PAM; however, HIV infection impairs this protective response. Protection against PAM is associated with the production of IgG specific for variant surface antigens (VSA-PAM) expressed by chondroitin sulfate A (CSA)-adhering parasitized erythrocytes (PEs). We hypothesized that VSA-PAM-specific IgG confers protection by promoting opsonic phagocytosis of PAM isolates and that HIV infection impairs this response. METHODS AND FINDINGS: We assessed the ability of VSA-PAM-specific IgG to promote opsonic phagocytosis of CSA-adhering PEs and the impact of HIV infection on this process. Opsonic phagocytosis assays were performed using the CSA-adherent parasite line CS2 and human and murine macrophages. CS2 PEs were opsonized with plasma or purified IgG subclasses from HIV-negative or HIV-infected PG and MG Kenyan women or sympatric men. Levels of IgG subclasses specific for VSA-PAM were compared in HIV-negative and HIV-infected women by flow cytometry. Plasma from HIV-negative MG women, but not PG women or men, promoted the opsonic phagocytosis of CSA-binding PEs (p < 0.001). This function depended on VSA-PAM-specific plasma IgG1 and IgG3. HIV-infected MG women had significantly lower plasma opsonizing activity (median phagocytic index 46 [interquartile range (IQR) 18-195] versus 251 [IQR 93-397], p = 0.006) and levels of VSA-PAM-specific IgG1 (mean fluorescence intensity [MFI] 13 [IQR 11-20] versus 30 [IQR 23-41], p < 0.001) and IgG3 (MFI 17 [IQR 14-23] versus 28 [IQR 23-37], p < 0.001) than their HIV-negative MG counterparts. CONCLUSIONS: Opsonic phagocytosis may represent a novel correlate of protection against PAM. HIV infection may increase the susceptibility of multigravid women to PAM by impairing this clearance mechanism.

Malaria and anaemia among pregnant women at first antenatal clinic visit in Kisumu, western Kenya.

OBJECTIVE: To determine the prevalence of malaria and anaemia among urban and peri-urban women attending their first antenatal clinic (ANC) in an area of perennial malaria transmission. METHODS: Between November 2003 and May 2004 we screened first ANC attenders for malaria and anaemia in a large urban hospital in Kisumu (western Kenya) and interviewed them to obtain demographic and medical information. RESULTS: Among the 685 study participants, prevalence of malaria parasitaemia was 18.0%, prevalence of any anaemia (haemoglobin < 11 g/dl) was 69.1% and prevalence of moderate anaemia was (haemoglobin < 8 g/dl) 11.8%. Sixteen women were hospitalized during pregnancy, eight because of malaria. In multivariate analysis, young age, living in a house with mud walls, a visit to rural area, peri-urban residence, second trimester of pregnancy and Luo ethnicity were significant risk factors for malaria parasitaemia. Malaria was an important risk factor for any and moderate anaemia; use of an insecticide-treated net (ITN) was a protective factor for any anaemia. Married women with a higher level of education, better-quality housing and full-time employment were more likely to use an ITN. CONCLUSION: Malaria and anaemia are established problems by the time of the first ANC visit. Mechanisms to deliver ITNs to women of child-bearing age before they become pregnant need to be explored. Early ANC visits are warranted in order for women to benefit from policies aimed at reducing the burden of malaria and anaemia.

Topography and malaria transmission heterogeneity in western Kenya highlands: prospects for focal vector control.

BACKGROUND: Recent resurgence of malaria in the highlands of Western Kenya has called for a more comprehensive understanding of the previously neglected complex highland vector ecology. Besides other drivers of malaria epidemiology, topography is likely to have a major effect on spatial vector and parasite distribution. The aim of this study was to determine the effects of topography on malaria spatial vector distribution and parasite prevalence. METHODOLOGY: Indoor resting adult malaria vectors and blood parasites were collected in three villages along a 4 km transect originating from the valley bottom and ending at the hilltop for 13 months. Members of the Anopheles gambiae complex were identified by PCR. Blood parasites were collected from children 6-13 years old and densities categorized by site of home location and age of the children. RESULTS: Ninety eight percent (98%) of An. gambiae s.s. and (99%) Anopheles funestus were collected in houses located at the edge of the valley bottom, whereas 1% of An. gambiae s.s. were collected at mid hill and at the hilltop respectively. No An. funestus were collected at the hilltop. Malaria prevalence was 68% at the valley bottom, 40.2% at mid hill and 26.7% at the hilltop. Children aged six years and living at the edge of the valley bottom had an annual geometric mean number of 66.1 trophozoites for every 200 white blood cells, while those living at mid-hill had a mean of 84.8, and those living at hilltop had 199.5 trophozoites. CONCLUSION: Malaria transmission in this area is mainly confined to the valley bottom. Effective vector control could be targeted at the foci. However, the few vectors observed at mid-hill maintained a relatively high prevalence rate. The higher variability in blood parasite densities and their low correlation with age in children living at the hilltop suggests a lower stability of transmission than at the mid-hill and valley bottom.

Use of antenatal services and delivery care among women in rural western Kenya: a community based survey.

BACKGROUND: Improving maternal health is one of the UN Millennium Development Goals. We assessed provision and use of antenatal services and delivery care among women in rural Kenya to determine whether women were receiving appropriate care. METHODS: Population-based cross-sectional survey among women who had recently delivered. RESULTS: Of 635 participants, 90% visited the antenatal clinic (ANC) at least once during their last pregnancy (median number of visits 4). Most women (64%) first visited the ANC in the third trimester; a perceived lack of quality in the ANC was associated with a late first ANC visit (Odds ratio [OR] 1.5, 95% confidence interval [CI] 1.0-2.4). Women who did not visit an ANC were more likely to have < 8 years of education (adjusted OR [AOR] 3.0, 95% CI 1.5-6.0), and a low socio-economic status (SES) (AOR 2.8, 95% CI 1.5-5.3). The ANC provision of abdominal palpation, tetanus vaccination and weight measurement were high (>90%), but provision of other services was low, e.g. malaria prevention (21%), iron (53%) and folate (44%) supplementation, syphilis testing (19.4%) and health talks (14.4%). Eighty percent of women delivered outside a health facility; among these, traditional birth attendants assisted 42%, laypersons assisted 36%, while 22% received no assistance. Factors significantly associated with giving birth outside a health facility included: age >or= 30 years, parity >or= 5, low SES, < 8 years of education, and > 1 hour walking distance from the health facility. Women who delivered unassisted were more likely to be of parity >or= 5 (AOR 5.7, 95% CI 2.8-11.6). CONCLUSION: In this rural area, usage of the ANC was high, but this opportunity to deliver important health services was not fully utilized. Use of professional delivery services was low, and almost 1 out of 5 women delivered unassisted. There is an urgent need to improve this dangerous situation.

Maternal Malaria and Malnutrition (M3) initiative, a pooled birth cohort of 13 pregnancy studies in Africa and the Western Pacific.

PURPOSE: The Maternal Malaria and Malnutrition (M3) initiative has pooled together 13 studies with the hope of improving understanding of malaria-nutrition interactions during pregnancy and to foster collaboration between nutritionists and malariologists. PARTICIPANTS: Data were pooled on 14 635 singleton, live birth pregnancies from women who had participated in 1 of 13 pregnancy studies. The 13 studies cover 8 countries in Africa and Papua New Guinea in the Western Pacific conducted from 1996 to 2015. FINDINGS TO DATE: Data are available at the time of antenatal enrolment of women into their respective parent study and at delivery. The data set comprises essential data such as malaria infection status, anthropometric assessments of maternal nutritional status, presence of anaemia and birth weight, as well as additional variables such gestational age at delivery for a subset of women. Participating studies are described in detail with regard to setting and primary outcome measures, and summarised data are available from each contributing cohort. FUTURE PLANS: This pooled birth cohort is the largest pregnancy data set to date to permit a more definite evaluation of the impact of plausible interactions between poor nutritional status and malaria infection in pregnant women on fetal growth and gestational length. Given the current comparative lack of large pregnancy cohorts in malaria-endemic settings, compilation of suitable pregnancy cohorts is likely to provide adequate statistical power to assess malaria-nutrition interactions, and could point towards settings where such interactions are most relevant. The M3 cohort may thus help to identify pregnant women at high risk of adverse outcomes who may benefit from tailored intensive antenatal care including nutritional supplements and alternative or intensified malaria prevention regimens, and the settings in which these interventions would be most effective.

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. The maternal HIV seroprevalence was 24.3%, and at delivery 22.0% of the women had evidence of malaria. Low birthweight, preterm delivery (PTD), intrauterine growth retardation (IUGR) and maternal anaemia (haemoglobin < 8 g/dl) occurred in 4.6, 6.7, 9.8 and 13.8% of deliveries, respectively. Maternal HIV, in the absence of malaria, was associated with a 99 g (95% CI 52-145) reduction in mean birthweight among all gravidae. Malaria was associated with both IUGR and PTD, resulting in a reduction in mean birthweight of 145 g (95% CI 82-209) among HIV-seronegative and 206 g (95% CI 115-298) among HIV-seropositive primigravidae, but not among multigravidae. Both HIV and malaria were significant risk factors for postpartum maternal anaemia, and HIV-seropositive women with malaria were twice as likely to have anaemia than HIV-seronegative women with or without malaria. CONCLUSION: Women with dual infection are at particular risk of adverse birth outcomes. In areas with a moderate or high prevalence of HIV and malaria, all pregnant women should be the focus of malaria and anaemia control efforts to improve birth outcomes.

HIV increases the risk of malaria in women of all gravidities in Kisumu, Kenya.

OBJECTIVE: To study the importance of HIV infection for malaria in pregnancy in Kisumu, Kenya. SUBJECTS AND METHODS: Healthy women with an uncomplicated pregnancy of 32 weeks or more attending the prenatal clinic in the Provincial Hospital between June 1996 and March 1999 were tested for HIV and malaria after consent had been obtained. For participating women who delivered in the same hospital, a blood smear of the mother and the placenta were obtained. RESULTS: In the third trimester, 5093 women consented to testing: the prevalence of malaria and HIV was 20.1 and 24.9%, respectively. Among the 2502 screened women who delivered in the hospital, the prevalence of HIV, peripheral parasitaemia and placental malaria was 24.5, 15.2, and 19.0%, respectively. Compared with HIV-seronegative women, HIV-seropositive women were more likely to be parasitaemic, to have higher parasite densities, and to be febrile when parasitaemic. Placental infections in HIV-seropositive women were more likely to be chronic, as indicated by the presence of moderate to heavy pigment depositions. When adjusted by age, the typical gravidity-specific pattern of malaria in pregnancy disappeared in HIV-seropositive women; HIV-seropositive primigravidae had a similar risk of malaria as HIV-seropositive multigravidae. The excess malaria attributable to HIV in the third trimester increased from 34.6% among HIV-seropositive primigravidae, to 41.5% among HIV-seropositive secundigravidae, and 50.7% among HIV-seropositive gravidae with three or more pregnancies. CONCLUSION: HIV infection alters patterns of malaria in pregnant women; in areas with both infections, all pregnant women should use malaria prevention.

Polymorphism of Fc receptor IIa for IgG in infants is associated with susceptibility to perinatal HIV-1 infection.

OBJECTIVE: To evaluate the effect of polymorphism of the Fc gamma receptor IIa, which is associated with differential human IgG subclass binding, on perinatal HIV-1 transmission. METHODS: Fc gamma RIIa genotype was tested in 448 HIV-seropositive mothers and their infants from a cohort study designed to assess the effect of placental malaria on HIV vertical transmission conducted from 1996 to 2001 in western Kenya. Fc gamma RIIa polymorphism was analyzed for associations with susceptibility to perinatal HIV infection and all-cause child mortality in HIV-positive children. RESULTS: Overall, 20% of infants were perinatally infected with HIV. There was no statistically significant association between maternal genotype and perinatal HIV-1 transmission. However, frequency of the infant Fc gamma RIIa His/His131 genotype was higher in HIV-positive compared with HIV-negative infants (35% and 21%, respectively), whereas the distribution was reversed (15% and 28%, respectively) for infants with the Fc gamma RIIa Arg/Arg131 genotype. Multivariate logistic regression controlling for maternal and infant confounding factors demonstrated that the odds of perinatal HIV infection in infants with the Fc gamma RIIa His/His131 versus Fc gamma RIIa His/Arg131 genotypes were significantly higher (adjusted odds ratio, 2.22; 95% confidence interval, 1.23-4.02; P = 0.009). There was no evidence for an association between HIV-positive child all-cause mortality and Fc gamma RIIa genotype. CONCLUSIONS: This study provides the first evidence that the infant Fc gamma RIIa His/His131 genotype is associated with susceptibility to perinatal HIV-1 transmission and further suggests that there is a dose-response relationship for the effect of the Fc gamma RIIa His131 gene on transmission.

Genetic diversity of HIV-1 in western Kenya: subtype-specific differences in mother-to-child transmission.

BACKGROUND: Little is known about the impact of HIV-1 group M subtypes on mother-to-child transmission (MTCT) of HIV-1 in African settings where multiple HIV-1 group M subtypes are co-circulating. OBJECTIVE: To assess the role of subtype variation on MTCT. METHODS: HIV-1-infected women attending an antenatal clinic in western Kenya were enrolled for a prospective study (1996-2000) of MTCT. HIV-1 subtype analysis of p24gag and gp41env identified potential recombinants, and their role in MTCT was determined. RESULTS: Among 414 women for whom HIV-1 subtype and HIV transmission status were available, MTCT occurred in 80 (19.3%). MTCT rates were higher among women with subtype D compared with subtype A in either the gp41 region [31.6 versus 16.1%, relative risk (RR) 2.0, P=0.002] or p24 region (29.9 versus 18.0%, RR 1.7, P=0.02). Discordant subtype combinations were identified in 103 of the women (25.9%), and were associated with higher rates of MTCT (28.2 versus 17.0%, RR 1.7, P=0.01). In multivariate analysis, women with subtype combinations D/D, D/A, and A/D had an increased risk of MTCT (adjusted odds ratios 3.5, 2.5, 6.2; P=0.005, 0.05, and 0.0003, respectively) compared with A/A women after adjustment for maternal HIV viral load, placental malaria infection, episiotomy or perineal tear, and low birthweight. CONCLUSION: MTCT appears to be more common among mothers infected with subtype D compared with subtype A. Such differences in MTCT frequency may be caused by altered cellular tropism for placental cell types.

Genetic diversity and high proportion of intersubtype recombinants among HIV type 1-infected pregnant women in Kisumu, western Kenya.

The high genetic diversity of HIV-1 continues to complicate effective vaccine development. To better understand the extent of genetic diversity, intersubtype recombinants and their relative contribution to the HIV epidemic in Kenya, we undertook a detailed molecular epidemiological investigation on HIV-1-infected women attending an antenatal clinic in Kisumu, Kenya. Analysis of gag-p24 region from 460 specimens indicated that 310 (67.4%) were A, 94 (20.4%) were D, 28 (6.1%) were C, 9 (2.0%) were A2, 8 (1.7%) were G, and 11 (2.4%) were unclassifiable. Analysis of the env -gp41 region revealed that 326 (70.9%) were A, 85 (18.5%) D, 26 (5.7%) C, 9 (2.0%) each of A2 and G, 4(0.9%) unclassifiable, and 1 (0.2%) CRF02_AG. Parallel analyses of the gag-p24 and env-gp41 regions indicated that 344 (74.8%) were concordant subtypes, while the remaining 116 (25.2%) were discordant subtypes. The most common discordant subtypes were D/A (40, 8.7%), A/D (27, 5.9%), C/A (11, 2.4%), and A/C (8, 1.7%). Further analysis of a 2.1-kb fragment spanning the gag-pol region from 38 selected specimens revealed that 19 were intersubtype recombinants and majority of them were unique recombinant forms. Distribution of concordant and discordant subtypes remained fairly stable over the 4-year period (1996-2000) studied. Comparison of amino acid sequences of gag-p24 and env-gp41 regions with the subtype A consensus sequence or Kenyan candidate vaccine antigen (HIVA) revealed minor variations in the immunodominant epitopes. These data provide further evidence of high genetic diversity, with subtype A as the predominant subtype and a high proportion of intersubtype recombinants in Kenya.

Malaria and human immunodeficiency virus infection as risk factors for anemia in infants in Kisumu, western Kenya.

The role of maternal and pediatric infection with human immunodeficiency virus type 1 (HIV-1) and malaria as risk factors for anemia was determined in a birth cohort of infants born to mothers participating in a study of the interaction between placental malaria and HIV infection, in Kisumu, Kenya. Between June 1996 and April 2000, 661 infants born to 467 HIV-seropositive and 194 HIV-seronegative mothers were monitored monthly from birth. At each visit a questionnaire was completed and a blood sample was collected for the determination of hemoglobin levels and detection of malaria and HIV. Anemia was common and increased from 13.6% at one month to 75% at six months and remained high throughout the second half of infancy. Placental malaria, infant malaria, and HIV infection of the infant were all associated with infant anemia in a multivariate model, adjusting for other co-variates found to be associated with infant anemia. The HIV-infected infants with malaria parasitemia had lower mean hemoglobin levels compared with HIV-uninfected infants, or HIV-infected infants without malaria, suggesting that HIV-infected infants are particularly vulnerable to the adverse consequences of malaria at this age. Early detection and prompt treatment of infant malaria and treatment of anemia as part of the study protocol failed to prevent most of the infants from becoming anemic. Although not proven effective in this study, micronutrient supplementation should be prospectively assessed in HIV-infected infants as a means of preventing anemia.

Risk factors for malaria in pregnancy in an urban and peri-urban population in western Kenya.

To assess risk factors for malaria in pregnancy in Kisumu, western Kenya, we studied healthy women with an uncomplicated pregnancy of > or = 32 weeks attending the antenatal clinic in the Provincial Hospital. Between June 1996 and March 1999, malaria and human immunodeficiency virus (HIV) infection were examined in 5093 pregnant women: 20.1% of the women were parasitaemic and 24.9% were HIV-seropositive. 2502 women delivered in the hospital and a smear was obtained: the prevalence of placental malaria, maternal peripheral parasitaemia, and HIV infection was respectively 19.0%, 15.2% and 24.5%. HIV infection (risk ratio [RR] 1.58, 95% confidence interval [95% CI] 1.32-1.89), young age (< 21 years: RR 1.51, 95% CI 1.19-1.91), being a primigravidae (RR 1.41, 95% CI 1.05-1.88), a peri-urban residence (RR 1.50, 95% CI 1.21-1.88), and Luo ethnicity (RR 1.74, 95% CI 1.35-2.24) were risk factors for malaria at delivery. Use of sulfadoxine-pyrimethamine (SP), reported by 2.1% of the women, was a protective factor (RR 0.44, 95% CI 0.18-1.06). Results were similar in the third trimester. In this urban/peri-urban setting, preventing HIV infection, delaying the first pregnancy until after adolescence, and applying an effective antimalarial strategy such as intermittent therapy with SP will reduce the prevalence of malaria in pregnancy.