Background HIV-1 surveys in defined populations identify underlying risks and trends useful to mount interventions. Goal The goal of the study was to determine HIV-1 prevalence and risk factors among men working at a Malawian sugar estate. Study Design Three independent surveys were conducted in 1994, 1997, and 1998. Procedures included obtaining informed consent, interviewing, and drawing blood for HIV and syphilis testing. Analyses determined prevalence of HIV and associated risk factors. Results HIV prevalence was 24.3% in 1994 (n = 1691), 22.8% in 1997 (n = 615), and 20.9% in 1998 (n = 1354;P < 0.03). From 1994 to 1998, the percentage of subjects with a history of sexually transmitted disease (STD) decreased from 43.6% to 29.5% (P < 0.0001), accompanied by a substantial rise in STDs confirmed by physical examination (from 7.5% to 16.8%;P < 0.0001) and by laboratory testing for syphilis (from 6.5% to 10.4%;P < 0.0001). The percentage with multiple sex partners declined (from 62.0% to 35.2%;P < 0.0001), and condom use rose (from 10.9% to 18.9%;P < 0.0001). STDs were significantly associated with prevalent HIV infection each year. Conclusions The prevalence of HIV has remained relatively stable and high in this cohort.

Abstract: Introduction: Although studies suggest that vitamin A or its metabolites influence the synthesis of erythropoietin in vitro and in animal models, it is unclear whether vitamin A supplementation increases plasma erythropoietin concentrations in humans. Objective: To determine whether daily vitamin A supplementation increases plasma erythropoietin concentrations in pregnant women with a high prevalence of anaemia. Methods: A randomized, double‐blind, controlled clinical trial was conducted to examine the effect of daily vitamin A (3000 µg retinol equivalent), iron (30 mg), and folate (400 µg) versus iron (30 mg) and folate (400 µg) (control) on haemoglobin and plasma erythropoietin concentrations in 203 pregnant women in Malawi, Africa. Results: Mean gestational age at enrollment was 23 wk, at which time 50% of the women were anaemic (haemoglobin <110 g/L). Mean (±SEM) change in haemoglobin from enrollment to 38 wk was 4.7±1.6 g/L (p=0.003) and 7.3±2.3 g/L (p=0.003) in the vitamin A and control groups, respectively. Mean change in plasma erythropoietin concentrations from enrollment to 38 wk was 2.39±5.00 (p=0.63) and −2.87±3.92 IU/L (p=0.46) in the vitamin A and controls groups, respectively. There were no significant differences between vitamin A and control groups in the slope of the regression line between log10 erythropoietin and haemoglobin at enrollment or 38 wk, and between enrollment and follow‐up within either group. Conclusions: Vitamin A supplementation does not appear to increase haemoglobin and plasma erythropoietin concentrations among pregnant women with a high prevalence of anaemia in Malawi.

Becker, Stephen*; Fisher, Alvan†; Flexner, Charles‡; Gerber, John G.§; Haubrich, Richard∥; Kashuba, Angela D. M.¶; Luber, Andrew D.#; Piscitelli, Stephen C.** Author Information

The relationships among hemoglobin, ferritin, and transferrin receptor levels and 2 markers of human immunodeficiency virus (HIV) disease severity--HIV load and CD4(+) lymphocyte count--were characterized among 483 pregnant women in Malawi, Africa. The only significant correlation was an inverse correlation between hemoglobin level and plasma HIV load (r=-.104; P<.03). The prevalence of iron deficiency anemia was not significantly different across quartiles of HIV load or CD4(+) lymphocyte count. In contrast to previous studies, these data suggest that iron status is not related to markers of HIV disease severity in pregnant women in Africa.

OBJECTIVE:To assess patterns of morbidity and associated factors in late infancy and early childhood among human immunodeficiency virus (HIV)-infected and -uninfected African children.DESIGN:Prospective study.SETTING:The Queen Elizabeth Central Hospital, Blantyre, Malawi.PARTICIPANTS:Children with known HIV status from an earlier perinatal intervention trial were enrolled during the first year of life and followed to approximately 36 months of age.OUTCOME MEASURES:Morbidity and mortality information was collected every 3 months by a questionnaire. A physical examination was conducted every 6 months. Blood to determine CD4(+) values was also collected. Age-adjusted and Kaplan-Meier analyses were performed to compare rates of morbidity and mortality among infected and uninfected children.RESULTS:Overall, 808 children (190 HIV-infected, 499 HIV-uninfected but born to infected mothers, and 119 born to HIV-uninfected mothers) were included in this study. Of these, 109 died during a median follow-up of 18 months. Rates of childhood immunizations were high among all children (eg, lowest was measles vaccination [87%] among HIV-infected children). Age-adjusted morbidity rates were significantly higher among HIV-infected than among HIV-uninfected children. HIV-infected children were more immunosuppressed than were uninfected children. By 3 years of age, 89% of the infected children died, 10% were in HIV disease category B or C, and only approximately 1% were without HIV symptoms. Among HIV-infected children, median survival after the first occurrence of acquired immunodeficiency syndrome-related conditions, such as splenomegaly, oral thrush, and developmental delay, was <10 months. These same conditions, in addition to frequent bouts of fever, were the main morbidity predictors of mortality.CONCLUSIONS:The frequency of diseases was high, and progression from asymptomatic or symptomatic HIV disease to death was rapid. Management strategies that effectively reduce morbidity for HIV-infected children are needed.

ObjectiveTo examine the association of viral load and CD4 lymphocyte count with mortality among HIV-infected children over one year of age. DesignA prospective study. HIV-infected children were enrolled during the first year of life and followed for more than 2 years at the Queen Elizabeth Central Hospital in Blantyre, Malawi (southeast Africa). MethodsMorbidity and mortality information was collected every 3 months, and physical examination and blood testing (for viral level and CD4 cell percentage) were performed every 6 months. Kaplan–Meier analyses and proportional hazards models were used to estimate survival and to examine the association of primary predictors with mortality. ResultsOf 155 HIV-infected children originally enrolled, 115 (74%) had viral load testing and 82 (53%) had both viral load and CD4 cell percentage testing after their first year. Among children over one year of age, significant associations were found between mortality and the log10 viral load and CD4 cell percentage in both univariate and multivariate models. Independent of the CD4 cell value, a one unit log10 increase in HIV RNA level increased the hazard of child mortality by more than twofold. Children with low CD4 cell counts (< 15%) and high viral loads (⩾ 250 000 copies/ml median value) had the worst survival; children with high CD4 cell counts (⩾ 15%) and low viral loads (< 250 000 copies/ml) had the best survival. ConclusionAs in developed countries, viral load and CD4 cell count are the main predictors of mortality among African children. Making these tests available adds to the challenges to be considered if antiviral therapies were to be adopted in these countries.

Breast milk vitamin A is not well characterized as an indicator of vitamin A status in women with infections. A controlled trial of vitamin A, 3 mg retinol equivalent/day, was conducted among 697 pregnant women with human immunodeficiency virus (HIV) infection in Malawi which allowed comparison of plasma versus breast milk vitamin A as indicators of vitamin A status. Retinol concentrations were measured in plasma at baseline (18-28 weeks) and 38 weeks gestation and breast milk at 6 weeks post-partum. Plasma alpha 1-acid glycoprotein (AGP) and C-reactive protein (CRP) were measured at baseline. Plasma retinol (geometric mean, SD) at 38 weeks was 0.72 (0.44, 1.18) and 0.61 (0.38, 0.98) mumol/L (P < 0.0002) and breast milk retinol was 1.32 (0.71, 2.43) and 0.95 (0.49, 1.82) mumol/L (P < 0.0001) in vitamin A and placebo groups, respectively. Women with elevated acute phase protein (AGP > 1 gm/L and/or CRP > 5 mg/L) at baseline who received vitamin A had significantly higher plasma and breast milk vitamin A at follow-up compared with placebo. Elevated acute phase proteins did not distinguish women with low body stores of vitamin A. Breast milk retinol appears to be a better indicator of vitamin A status than plasma retinol in women with infections.

Background: Although anemia is highly prevalent during pregnancy and is common during human immunodeficiency virus (HIV) infection, anemia and iron status have not been well characterized in HIV-infected pregnant women. Objective: To gain insight into iron status in HIV-infected pregnant women using plasma transferrin receptor and related indicators of anemia. Study design: Plasma transferrin receptor, ferritin, α1-acid glycoprotein, C-reactive protein and hemoglobin concentrations were measured in pregnant women, gestational age 18–28 weeks, seen in an urban antenatal clinic in Blantyre, Malawi. Results: The prevalence of anemia among 662 HIV-positive and 190 HIV-negative pregnant women was 73.1% and 50.0%, respectively (P<0.0001). Among HIV-positive and HIV-negative women, median plasma transferrin receptor concentrations were 24.4 and 24.1 nmol/l (P=0.5), respectively, and median plasma ferritin concentrations were 17.8 and 20.8 µg/l (P<0.05), respectively. There was a large overlap in plasma transferrin receptor concentrations among women with and without anemia. Using the combination of hemoglobin and ferritin as a standard, the sensitivity and specificity of plasma transferrin receptor in diagnosing iron deficiency anemia was estimated at 45.9% and 68.1%, respectively. Conclusion: The use of plasma transferrin receptor concentrations as an indicator of iron deficiency anemia may be limited in pregnant women with chronic inflammation and infection. Sponsorship: The National Institutes of Health (HD32247, HD30042, HIVNET contract N01-AI-35173-117), the Fogarty International Center, and the United States Agency for International Development (Cooperative Agreement HRN-A-00-97-00015-00). European Journal of Clinical Nutrition (2000) 54, 872–877

Background. HIV-infected and uninfected children who survived their first year of life were prospectively followed in Malawi to assess levels of mortality and related risk factors during the second and third years of life. Methods. Children with known HIV status from an earlier perinatal intervention trial were enrolled. These children [HIV-infected (Group A); HIV-uninfected but born to HIV-seropositive mothers (Group B); and children born to HIV-seronegative mothers (Group C)] were followed every 3 months until age 36 months. Mortality data were collected at each visit. Immunologic data (CD4+ percent) were collected at or immediately after enrollment. Results. Overall 702 children were enrolled and 83 children died during follow-up. The mortality rate per 1000 person years of observation was 339.3 among Group A children, 46.3 among Group B children and 35.7 among Group C children. Among HIV-infected children the cumulative proportion surviving to age 24 months was 70% and those surviving to age 36 months was 55%. By age 32 months none of the severely immunosuppressed (CD4% <15%) children had survived. The mortality differentials between HIV-infected and uninfected children persisted after adjusting for several risk factors. The major causes of death among infected children (n = 52) were wasting and respiratory conditions. Conclusions. Although all HIV-infected children had received childhood immunizations, mortality was high. Management of these children should include aggressive antimicrobial treatment, and evaluation of prophylactic regimens should be considered.

OBJECTIVE:To characterise the major plasma carotenoids in pregnant women with and without HIV infection attending antenatal clinic in Blantyre, Malawi.DESIGN:A cross sectional study.SETTING:Antenatal clinic of Queen Elizabeth Central Hospital, Blantyre, Malawi.SUBJECTS:Nine hundred women (697 HIV-positive and 203 HIV-negative women) in their second trimester of pregnancy.MAIN OUTCOME MEASURES:Plasma carotenoid levels as related to HIV status and level of disease progression.RESULTS:There were no significant differences in plasma carotenoid levels between HIV-positive and HIV-negative women. Median (25th, 75th percentiles) plasma levels of carotenoids for all women in the study were alpha-carotene, 0.040 (0.23, 0.071) mumol/L; beta-carotene, 0.350 (0.192, 0.595) mumol/L; beta-cryptoxanthin, 0.050 (0.029, 0.091) mumol/L; lutein/zeaxanthin 0.646 (0.426, 0.976) mumol/L; lycopene, 0.088 (0.055, 0.138) mumol/L, and total carotenoids 1.321 (0.884, 1.874) mumol/L. Mothers had higher mean plasma concentrations of alpha-carotene (p < 0.04), beta-carotene (p < 0.0001), lutein/zeaxanthin (p < 0.0001), and total carotenoids (p < 0.0001) in the wet season than the dry season. No seasonality was observed for beta-cryptoxanthin, lycopene, or retinol.CONCLUSION:This study suggests that pregnant women with and without HIV infection in Blantyre, Malawi have relatively low plasma carotenoid levels and poor dietary intake of provitamin A carotenoids.

Understanding the risk of human immunodeficiency virus (HIV) transmission through breastfeeding is essential for advising HIV-infected mothers and formulating public health policy recommendations.To measure the frequency, timing, and risk factors of HIV transmission through breast milk.Prospective cohort study conducted between 1994 and 1997, with follow-up of infants through 24 months of age.Postnatal clinic of tertiary care hospital, Blantyre, Malawi.A total of 672 infants (HIV-negative at birth) born to HIV-infected women who had not received antiretroviral drugs during or after pregnancy.Incidence of HIV in breastfed infants by age and maternal and infant risk factors for HIV transmission, using proportional hazard models to derive risk ratios (RRs) and 95% confidence intervals (CIs).Forty-seven children became HIV-infected while breastfeeding but none after breastfeeding had stopped. The cumulative infection rate while breastfeeding, from month 1 to the end of months 5, 11,17, and 23, was 3.5%, 7.0%, 8.9%, and 10.3%, respectively. Incidence per month was 0.7% during age 1 to 5 months, 0.6% during age 6 to 11 months, and 0.3% during age 12 to 17 months (P = .01 for trend). The only factors significantly associated with low risk of postnatal HIV transmission in a multivariate model were high maternal parity (RR, 0.23; 95% CI, 0.09-0.56) and older maternal age (RR, 0.44; 95% CI, 0.23-0.84).Our data suggest that the risk of HIV infection is highest in the early months of breastfeeding, which should be considered in formulating breastfeeding policy recommendations.

ABSTRACTAlthough an elevated sodium concentration in human milk is suggested to be an indicator of mastitis, it is unclear whether elevated sodium concentrations are associated with immunological and inflammatory mediators in human milk. We conducted a cross-sectional study to evaluate the relationships between elevated breast milk sodium concentrations and levels of lactoferrin, lysozyme, secretory leukocyte protease inhibitor (SLPI), interleukin-8 (IL-8), and RANTES (regulated on activation normal T cell expressed and secreted) in human milk at 6 weeks postpartum in 96 lactating women in Blantyre, Malawi. Mastitis, as indicated by an elevated breast milk sodium concentration, was present in 15.6% of the women. Women with and without mastitis had respective median levels of other factors as follows: lactoferrin, 1,230 versus 565 mg/liter (P< 0.0007); lysozyme, 266 versus 274 mg/liter (P= 0.55); SLPI, 76 versus 15 μg/liter, (P< 0.0002); IL-8, 339 versus 25 ng/liter (P< 0.0001); and RANTES, 82 versus 3 ng/liter (P< 0.0001). Elevated sodium concentrations in breast milk are associated with an increase in levels of some immunological and inflammatory factors in breast milk.

Human immunodeficiency virus (HIV) type 1 load in breast milk and mastitis were examined as risk factors for vertical transmission of HIV-1. Six weeks after delivery, HIV-1 load and sodium (an indicator of mastitis) were measured in breast milk from 334 HIV-1-infected women in Malawi. Median breast milk HIV-1 load was 700 copies/mL among women with HIV-1-infected infants versus undetectable (<200 copies/mL) among those with uninfected infants, respectively (P<. 0001). Elevated breast milk sodium levels consistent with mastitis occurred in 16.4% of HIV-1-infected women and were associated with increased vertical transmission of HIV-1 (P<.0001). Median breast milk HIV-1 load was 920 copies/mL among women with versus undetectable among those without elevated breast milk sodium levels, respectively (P<.0001). Mastitis and breast milk HIV-1 load may increase the risk of vertical transmission of HIV-1 through breast-feeding.

CONTEXT:Understanding the risk of human immunodeficiency virus (HIV) transmission through breastfeeding is essential for advising HIV-infected mothers and formulating public health policy recommendations. OBJECTIVE:To measure the frequency, timing, and risk factors of HIV transmission through breast milk. DESIGN:Prospective cohort study conducted between 1994 and 1997, with follow-up of infants through 24 months of age. SETTING:Postnatal clinic of tertiary care hospital, Blantyre, Malawi. PARTICIPANTS:A total of 672 infants (HIV-negative at birth) born to HIV-infected women who had not received antiretroviral drugs during or after pregnancy. MAIN OUTCOME MEASURE:Incidence of HIV in breastfed infants by age and maternal and infant risk factors for HIV transmission, using proportional hazard models to derive risk ratios (RRs) and 95% confidence intervals (CIs). RESULTS:Forty-seven children became HIV-infected while breastfeeding but none after breastfeeding had stopped. The cumulative infection rate while breastfeeding, from month 1 to the end of months 5, 11,17, and 23, was 3.5%, 7.0%, 8.9%, and 10.3%, respectively. Incidence per month was 0.7% during age 1 to 5 months, 0.6% during age 6 to 11 months, and 0.3% during age 12 to 17 months (P = .01 for trend). The only factors significantly associated with low risk of postnatal HIV transmission in a multivariate model were high maternal parity (RR, 0.23; 95% CI, 0.09-0.56) and older maternal age (RR, 0.44; 95% CI, 0.23-0.84). CONCLUSIONS:Our data suggest that the risk of HIV infection is highest in the early months of breastfeeding, which should be considered in formulating breastfeeding policy recommendations.

Disturbances of vaginal flora are common among women of reproductive age. In areas of sub-Saharan Africa where the prevalence of HIV is high, the frequency of bacterial vaginosis (BV) is also high. In this study, we assessed the association of BV and other disturbances of vaginal flora with prevalent HIV infection in two cross-sectional studies among pregnant women in urban Malawi. The prevalence of HIV-1 was 23% in 1990 and 30% in 1993. Overall, 30% of the women had BV, 59% had mild or moderate disturbance of vaginal flora, and only 11% had normal vaginal flora. Increasing prevalence of HIV was significantly associated with increasing severity of disturbance of vaginal flora (p < .00001, chi2 trend test). This trend of increased prevalence persisted after controlling for concurrent sexually transmitted diseases (STDs), sexual activity, and socioeconomic factors. After multivariate adjustment for potential confounders, the odds ratio for the association of BV with prevalent HIV infection was 3.0 (95% confidence interval [CI], 2.4-3.8), that of moderate vaginal disturbance with HIV infection was 2.2 (95% CI, 1.7-2.8), and that of mild vaginal disturbance with HIV infection was 1.6 (95% CI, 1.3-2.1). Among women with BV, HIV infection was higher among younger women than older, implying more recent infection. Although these studies were cross-sectional, our data suggest that BV could be associated with increased susceptibility to HIV infection.

Human milk contains important immunological factors that protect the breast from infection and are thought to protect infants from infection, including human immunodeficiency virus (HIV) infection. Human milk immunological factors have not been well characterized in HIV-infected lactating women. Lysozyme, secretory leukocyte protease inhibitor (SLPI), sodium (an indicator of mastitis), and HIV were measured in breast milk of 334 HIV-infected women at 6 weeks postpartum. Women with mastitis, as indicated by elevated breast milk sodium concentrations, had higher median levels lysozyme (290 vs 221 mg/L, p < 0.04), SLPI (38 vs 19 mg/L, p < 0.0001) and HIV (920 copies/mL vs undetectable, p < 0.0001) compared with women without mastitis. Lower total plasma carotenoid levels (p < 0.02) and higher maternal HIV load (p < 0.006) by quartile were risk factors for mastitis. Mastitis, as indicated by elevated breast milk sodium levels, is associated with high concentrations of immunological factors and higher HIV load in breast milk.

OBJECTIVES:To examine rates of HIV-1 and sexually transmitted disease (STD) among pregnant and postpartum women in urban Malawi, Africa. DESIGN:Serial cross-sectional surveys and a prospective study. METHODS:Three major surveys were conducted in 1990, 1993 and 1994/1995. Consecutive first-visit antenatal women and women giving birth at the Queen Elizabeth Central Hospital were tested for HIV and STD after counseling and obtaining informed consent. Unlinked, anonymous HIV testing was also conducted on smaller samples of antenatal women in the same hospital to provide annual prevalence data. HIV-seronegative postpartum women from the 1990 and 1993 surveys were enrolled in a prospective study to determine HIV incidence. RESULTS:HIV seroprevalence rose from 2.0% in 1985 to 32.8% in 1996, a 16-fold increase. The highest age-specific HIV prevalence was in the following age-groups: 20-24 years during 1990, 25-29 years during 1993, and 30-34 years during 1996. Among 1173 women followed for a median of 30.9 months, HIV incidence was 5.98 per 100 person-years in women aged < 20 years and declined steadily in older women. The prevalence of STD significantly declined among both HIV-positive and negative women. This decline in STD prevalence, however, was not accompanied by increased condom use over time. CONCLUSIONS:Among urban childbearing women in Malawi, incidence of HIV is highest among young women while, currently, prevalence is highest among older women. Recent declines in STD prevalence suggest that HIV prevention programs are having an impact either through improved STD diagnosis and treatment or reduced risk behaviors. Sequential cross-sectional STD prevalence measures may be useful in monitoring effectiveness of STD and HIV prevention activities.

Background:Cross-sectional studies suggest an association between bacterial vaginosis (BV) and HIV-1 infection. However, an assessment of a temporal effect was not possible. Objectives:To determine the association of BV and other disturbances of vaginal flora with HIV seroconversion among pregnant and postnatal women in Malawi, Africa. Design:Longitudinal follow-up of pregnant and postpartum women. Methods:Women attending their first antenatal care visit were screened for HIV after counselling and obtaining informed consent. HIV-seronegative women were enrolled and followed during pregnancy and after delivery. These women were again tested for HIV at delivery and at 6-monthly visits postnatally. Clinical examinations and collection of laboratory specimens (for BV and sexually transmitted diseases) were conducted at screening and at the postnatal 6-monthly visits. The diagnosis of BV was based on clinical criteria. Associations of BV and other risk factors with HIV seroconversion, were examined using contingency tables and multiple logistic regression analyses on antenatal data, and Kaplan–Meier proportional hazards analyses on postnatal data. Results:Among 1196 HIV-seronegative women who were followed antenatally for a median of 3.4 months, 27 women seroconverted by time of delivery. Postnatally, 97 seroconversions occurred among 1169 seronegative women who were followed for a median of 2.5 years. Bacterial vaginosis was significantly associated with antenatal HIV seroconversion (adjusted odds ratio = 3.7) and postnatal HIV seroconversion (adjusted rate ratio = 2.3). There was a significant trend of increased risk of HIV seroconversion with increasing severity of vaginal disturbance among both antenatal and postnatal women. The approximate attributable risk of BV alone was 23% for antenatal HIV seroconversions and 14% for postnatal seroconversions. Conclusions:This prospective study suggests that progressively greater disturbances of vaginal flora, increase HIV acquisition during pregnancy and postnatally. The screening and treating of women with BV could restore normal flora and reduce their susceptibility to HIV.