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.

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.

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.

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.

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.

Risk factors for inadequate TB case finding in Rural Western Kenya: a comparison of actively and passively identified TB patients.

BACKGROUND: The findings of a prevalence survey conducted in western Kenya, in a population with 14.9% HIV prevalence suggested inadequate case finding. We found a high burden of infectious and largely undiagnosed pulmonary tuberculosis (PTB), that a quarter of the prevalent cases had not yet sought care, and a low case detection rate. OBJECTIVE AND METHODS: We aimed to identify factors associated with inadequate case finding among adults with PTB in this population by comparing characteristics of 194 PTB patients diagnosed in a health facility after self-report, i.e., through passive case detection, with 88 patients identified through active case detection during the prevalence survey. We examined associations between method of case detection and patient characteristics, including HIV-status, socio-demographic variables and disease severity in univariable and multivariable logistic regression analyses. FINDINGS: HIV-infection was associated with faster passive case detection in univariable analysis (crude OR 3.5, 95% confidence interval (CI) 2.0-5.9), but in multivariable logistic regression this was largely explained by the presence of cough, illness and clinically diagnosed smear-negative TB (adjusted OR (aOR) HIV 1.8, 95% CI 0.85-3.7). Among the HIV-uninfected passive case detection was less successful in older patients aOR 0.76, 95%CI 0.60-0.97 per 10 years increase), and women (aOR 0.27, 95%CI 0.10-0.73). Reported current or past alcohol use reduced passive case detection in both groups (0.42, 95% CI 0.23-0.79). Among smear-positive patients median durations of cough were 4.0 and 6.9 months in HIV-infected and uninfected patients, respectively. CONCLUSION: HIV-uninfected patients with infectious TB who were older, female, relatively less ill, or had a cough of a shorter duration were less likely found through passive case detection. In addition to intensified case finding in HIV-infected persons, increasing the suspicion of TB among HIV-uninfected women and the elderly are needed to improve TB case detection in Kenya.

Integrated community-directed intervention for schistosomiasis and soil transmitted helminths in western Kenya - a pilot study.

BACKGROUND: Schistosome and soil-transmitted helminth (STH) infections are recognized as major global public health problems, causing severe and subtle morbidity, including significant educational and nutritional effects in children. Although effective and safe drugs are available, ensuring access to these drugs by all those at risk of schistosomiasis and STHs is still a challenge. Community-directed intervention (CDI) has been used successfully for mass distribution of drugs for other diseases such as onchocerciasis and lymphatic filariasis. A national control programme is yet to be instituted in Kenya and evidence for cost-effective strategies for reaching most affected communities is needed. This study evaluated the effectiveness and feasibility of the CDI strategy in the control of schistosomiasis and STHs, in East Uyoma location, Rarieda district, a community of western Kenya that is highly endemic for both infections. RESULTS: Pre-treatment prevalence of S. mansoni averaged 17.4% (range 5-43%) in the entire location. Treatment coverage in different villages ranged from 54.19 to 96.6% by community drug distributor (CDD) records. Assessment from a household survey showed coverage of 52.3 -91.9% while the proportion of homesteads (home compounds) covered ranged from 54.9-98.5%. Six months after one round of drug distribution, the prevalence levels of S. mansoni, hookworm and Trichuris trichura infections were reduced by 33.2%, 69.4% and 42.6% respectively. CONCLUSIONS: This study shows that CDI is an accepted and effective strategy in the mass treatment of schistosomiasis and STH infections in resource constrained communities in Kenya and may be useful in similar communities elsewhere. A controlled trial comparing CDI and school based mass drug administration to demonstrate their relative advantages is ongoing.

Diarrhea in children less than two years of age with known HIV status in Kisumu, Kenya.

OBJECTIVE: To compare the frequency and etiology of diarrhea in children aged less than 2 years with known HIV status. METHODS: This was a nested cohort study, whereby children were followed during monthly routine and unscheduled visits. The HIV status of children was determined with PCR. A stool culture was obtained from children with diarrhea. A subset of stool samples was examined for parasites and tested for rotavirus. RESULTS: Between 1997 and 2001, 682 children (51.0% male) contributed observation periods with a mean of 47 weeks. Overall there were 198 episodes of diarrhea per 100 child-years of observation (CYO); diarrhea was more common among HIV-positive children than among HIV-negative children (321 vs. 183 episodes/100 CYO, respectively, p<0.01) and was not statistically different for HIV-negative children born to HIV-positive compared with HIV-negative mothers (182 vs. 187 episodes/100 CYO, respectively, p=0.36). For 66.5% of the acute episodes a stool culture was obtained; 27.8% of stool cultures yielded a bacterial pathogen. A positive stool culture was less likely among HIV-positive children compared to children of HIV-negative mothers (20.5% vs. 34.3%, p=0.01). Susceptibility of Salmonella and Shigella to commonly used antibiotics was low. Rotavirus was detected in 13.9% of 202 examined stool samples, and a stool parasite in 3.8% of 394 samples. Diarrhea was associated with 37.8% of child deaths. CONCLUSIONS: Diarrhea was more common among HIV-infected children, but was not associated with specific bacterial pathogens. Measures that reduce diarrhea will benefit all children, but may benefit HIV-infected children in particular.

Geohelminth Infections among pregnant women in rural western Kenya; a cross-sectional study.

BACKGROUND: Geohelminth infections are common in rural western Kenya, but risk factors and effects among pregnant women are not clear. METHODOLOGY: During a community-based cross-sectional survey, pregnant women were interviewed and asked to provide a blood sample and a single fecal sample. Hemoglobin was measured and a blood slide examined for malaria. Geohelminth infections were identified using the concentration and Kato-Katz method. RESULTS: Among 390 participants who provided a stool sample, 76.2% were infected with at least one geohelminth: 52.3% with Ascaris lumbricoides, 39.5% with hookworm, and 29.0% with Trichuris trichiura. Infection with at least one geohelminth species was associated with the use of an unprotected water source (adjusted odds ratio [AOR] 1.8, 95% confidence interval [CI] 1.1-3.0) and the lack of treatment of drinking water (AOR 1.8, 95% CI 1.1-3.1). Geohelminth infections were not associated with clinical symptoms, or low body mass index. A hookworm infection was associated with a lower mid upper arm circumference (adjusted mean decrease 0.7 cm, 95% CI 0.3-1.2 cm). Hookworm infections with an egg count > or =1000/gram feces (11 women) were associated with lower hemoglobin (adjusted mean decrease 1.5 g/dl, 95% CI 0.3-2.7). Among gravidae 2 and 3, women with A. lumbricoides were less likely to have malaria parasitemia (OR 0.4, 95% CI 0.2-0.8) compared to women without A. lumbricoides, unlike other gravidity groups. CONCLUSION: Geohelminth infections are common in this pregnant population; however, there were few observed detrimental effects. Routine provision of antihelminth treatment during an antenatal clinic visit is recommended, but in this area an evaluation of the impact on pregnancy, malaria, and birth outcome is useful.

Plasma folate level and high-dose folate supplementation predict sulfadoxine-pyrimethamine treatment failure in pregnant women in Western kenya who have uncomplicated malaria.

UNLABELLED: Sulfadoxine-pyrimethamine (SP) inhibits folate metabolism by the malaria parasite. We investigated the association between folate levels and SP failure in pregnant women. Data from a trial to assess the effect that folate supplementation has on SP failure in 467 pregnant women were analyzed. Plasma folate levels were determined at enrollment and at day 7. High baseline folate levels, high parasite densities, and age <20 years were risk factors for SP failure. High-dose (5 mg daily) folate supplementation or high folate levels at day 7 were independent risk factors. Therefore, pregnant women receiving SP should receive low-/moderate-dose folate supplementation. TRIAL REGISTRATION: http://www.clinicaltrials.gov identifier: NCT00130065.

Effect of placental malaria and HIV infection on the antibody responses to Plasmodium falciparum in infants.

BACKGROUND: Placental malaria (PM) and maternal infection with human immunodeficiency virus (HIV) type 1 have been shown to affect infant morbidity and immune responses to Plasmodium falciparum. We studied the effects of PM and HIV infection on the antimalarial antibody responses and morbidity outcomes of infants throughout the first year of life. METHODS: A total of 411 Kenyan infants who were born to mothers who were singly or dually infected with PM and/or HIV had their levels of immunoglobulin G antibody to 6 P. falciparum antigens/epitopes (apical membrane antigen-1, erythrocyte-binding antigen-175; liver-stage antigen-1 [LSA-1], circumsporozoite protein [CSP], merozoite surface protein-2, and rhoptry-associated protein-1 [RAP-1]) and to tetanus toxoid (TT) tested using enzyme-linked immunosorbent assay. RESULTS: PM had little effect on the antibody responses of infants, whereas maternal HIV infection resulted in decreased levels of antibody to LSA-1, CSP, and RAP-1 epitopes at birth, compared with the absence of PM and maternal HIV infection (P = .0063). Levels of antibodies to TT were significantly reduced in infants born to mothers coinfected with HIV and PM, compared with the levels noted in infants born to HIV-negative mothers (P = .0003). In HIV-infected infants, levels of antibody to TT were reduced, but levels of antibody to malarial antigens were not. Antimalarial antibody levels were positively associated with malaria-related morbidity outcomes. CONCLUSION: Infant HIV infection and maternal coinfection with HIV and PM negatively influence antibody responses to TT, but not those to malarial antigens, in infants. Antimalarial antibodies rarely showed protective associations with morbidity in infants and were more often a marker for malaria exposure and risk of infection.

Pharmacokinetics of sulfadoxine-pyrimethamine in HIV-infected and uninfected pregnant women in Western Kenya.

BACKGROUND: Sulfadoxine-pyrimethamine (SP) is among the most commonly used antimalarial drugs during pregnancy, yet the pharmacokinetics of SP are unknown in pregnant women. HIV-infected (HIV(+)) women require more frequent doses of intermittent preventive therapy with SP than do HIV-uninfected (HIV(-)) women. We investigated whether this reflects their impaired immunity or an HIV-associated alteration in the disposition of SP. METHODS: Seventeen pregnant HIV(-) women and 16 pregnant HIV(+) women received a dose of 1500 mg of sulfadoxine and 75 mg of pyrimethamine. Five HIV(-) and 6 HIV(+) postpartum women returned 2-3 months after delivery for another dose. The pharmacokinetics of sulfadoxine and pyrimethamine were compared between these groups. RESULTS: HIV status did not affect the area under the curve (AUC(0-->infinity)) or the half-lives of sulfadoxine or pyrimethamine in prepartum or postpartum women, although partum status did have a significant affect on sulfadoxine pharmacokinetics. Among prepartum women, the median half-life for sulfadoxine was significantly shorter than that observed in postpartum women (148 vs 256 h; P<.001), and the median AUC(0-->infinity) was ~40% lower (22,816 vs 40,106 microg/mL/h, P<.001). HIV status and partum status did not show any significant influence on pyrimethamine pharmacokinetics. CONCLUSION: Pregnancy significantly modifies the disposition of SP, whereas HIV status has little influence on pharmacokinetic parameters in pregnant women.

HIV, malaria, and infant anemia as risk factors for postneonatal infant mortality among HIV-seropositive women in Kisumu, Kenya.

BACKGROUND: HIV and malaria in sub-Saharan Africa are associated with poor pregnancy outcome and infant survival. We studied the association of placental malaria, infant malaria and anemia, and infant HIV status with postneonatal infant mortality (PNIM) among infants of HIV-seropositive women. METHODS: During 1996-2001, infants born to 570 HIV-seropositive mothers in Kisumu, Kenya were monitored monthly for malaria (parasitemia or clinical malaria) and anemia (hemoglobin level <8 g/dL) and vital status. RESULTS: Thirty-nine deaths occurred among 112 HIV-positive infants (420/1000 live births [LBs] [95% confidence interval {CI}, 318-522 LBs]), and 36 occurred among 458 HIV-negative infants (99/1000 LBs [95% CI, 68-130 LBs]) (P<.001). In multivariate Cox regression analysis among HIV-negative infants, PNIM was associated with infant anemia (adjusted hazard ratio [AHR], 5.03 [95% CI, 1.97-12.81]) but not with placental malaria (AHR, 1.22 [95% CI, 0.50-2.95]) or infant malaria (AHR, 0.35 [95% CI, 0.10-1.21]). Among HIV-positive infants, neither placental malaria (AHR, 0.34 [95% CI, 0.10-1.10]) nor infant malaria (AHR, 0.31 [95% CI, 0.07-1.33]) or anemia (AHR, 1.07 [95% CI, 0.32-3.61]) was significantly associated with PNIM. CONCLUSION: In this study population, placental malaria and infant parasitemia were not risk factors for PNIM among infants of HIV-seropositive women. The prevention of infant anemia may decrease PNIM among HIV-negative infants of HIV-seropositive women.

Effect of haematinic supplementation and malaria prevention on maternal anaemia and malaria in western Kenya.

OBJECTIVE: To evaluate the effect of routine antenatal haematinic supplementation programmes and intermittent preventive treatment (IPT) with sulphadoxine-pyrimethamine (SP) in Kenya. METHODS: Anaemia [haemoglobin (Hb) <11 g/dl), severe anaemia (Hb <8 g/dl) and placental malaria were compared among women with known HIV status who delivered at a provincial hospital after study enrolment in the third trimester during three consecutive periods: period 1, no routine intervention (reference); period 2, routine haematinic supplementation (60 mg elementary iron three times/day, folic acid 5 mg once daily) and period 3, haematinics and IPT with SP. RESULTS: Among 3108 participants, prevalence of placental malaria, anaemia and severe anaemia postpartum was 16.7%, 53.6% and 12.7%, respectively. Compared with period 1, women in period 2 were less anaemic [adjusted odds ratio (AOR), 95% confidence interval anaemia: 0.56, 0.47-0.67; severe anaemia 0.37, 0.28-0.49] and shared a similar prevalence of placental malaria (AOR 1.07, 0.86-1.32). Women in period 3 were also less anaemic (AOR anaemia: 0.43, 0.35-0.53 and severe anaemia: 0.43, 0.31-0.59), and had less placental malaria (AOR 0.56, 0.42-0.73). The effect of intervention did not differ significantly by HIV status. CONCLUSION: The haematinic supplementation programme was associated with significant reductions in anaemia in HIV-seropositive and HIV-seronegative women. The subsequent introduction of IPT was associated with halving of malaria, but no additional haematological benefit over haematinics.

A randomized controlled trial of folate supplementation when treating malaria in pregnancy with sulfadoxine-pyrimethamine.

OBJECTIVES: Sulfadoxine-pyrimethamine (SP) is an antimalarial drug that acts on the folate metabolism of the malaria parasite. We investigated whether folate (FA) supplementation in a high or a low dose affects the efficacy of SP for the treatment of uncomplicated malaria in pregnant women. DESIGN: This was a randomized, placebo-controlled, double-blind trial. SETTING: The trial was carried out at three hospitals in western Kenya. PARTICIPANTS: The participants were 488 pregnant women presenting at their first antenatal visit with uncomplicated malaria parasitaemia (density of >or= 500 parasites/microl), a haemoglobin level higher than 7 g/dl, a gestational age between 17 and 34 weeks, and no history of antimalarial or FA use, or sulfa allergy. A total of 415 women completed the study. INTERVENTIONS: All participants received SP and iron supplementation. They were randomized to the following arms: FA 5 mg, FA 0.4 mg, or FA placebo. After 14 days, all participants continued with FA 5 mg daily as per national guidelines. Participants were followed at days 2, 3, 7, 14, 21, and 28 or until treatment failure. OUTCOME MEASURES: The outcomes were SP failure rate and change in haemoglobin at day 14. RESULTS: The proportion of treatment failure at day 14 was 13.9% (19/137) in the placebo group, 14.5% (20/138) in the FA 0.4 mg arm (adjusted hazard ratio [AHR], 1.07; 98.7% confidence interval [CI], 0.48 to 2.37; p = 0.8), and 27.1% (38/140) in the FA 5 mg arm (AHR, 2.19; 98.7% CI, 1.09 to 4.40; p = 0.005). The haemoglobin levels at day 14 were not different relative to placebo (mean difference for FA 5 mg, 0.17 g/dl; 98.7% CI, -0.19 to 0.52; and for FA 0.4 mg, 0.14 g/dl; 98.7% CI, -0.21 to 0.49). CONCLUSIONS: Concomitant use of 5 mg FA supplementation compromises the efficacy of SP for the treatment of uncomplicated malaria in pregnant women. Countries that use SP for treatment or prevention of malaria in pregnancy need to evaluate their antenatal policy on timing or dose of FA supplementation.

Placental malaria diminishes development of antibody responses to Plasmodium falciparum epitopes in infants residing in an area of western Kenya where P. falciparum is endemic.

To determine the effect of placental malaria (PM) infection on the development of antibody responses to malaria in infants, we measured immunoglobulin G levels to seven different Plasmodium falciparum epitopes by using plasma samples collected at monthly intervals from infants born to mothers with and without PM. Overall, PM was associated with diminished antibody levels to all of the epitopes tested, especially with infants aged >or=4 to 12 months, and the difference was statistically significant for four of the seven epitopes (P<0.0035). These findings suggest that PM can negatively influence the development of immune responses to malaria in infants.