John D. Chiphangwi

Bacterial vaginosis and disturbances of vaginal flora : association with increased acquisition of HIV

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.

Maternal vitamin A deficiency and mother-to-child transmission of HIV-1

Studies show that around 10-40% HIV-positive women will give birth to children who are also infected. However, the risk factors for transmission from mother to child are not well understood and the effects of maternal nutritional status are unknown. We conducted a study of vitamin A status in pregnant women as a risk factor for mother-to-child transmission of HIV in Malawi. Serum vitamin A, height, weight, CD4 T-cell counts, and duration of breastfeeding were measured in 338 HIV-positive mothers whose infants HIV serostatus was known. Mother-to-child transmission of HIV was 21.9% among mothers whose infants survived to 12 months of age. Mean vitamin A concentration in 74 mothers who transmitted HIV to their infants was lower than that in 264 mothers who did not transmit HIV to their infants (0.86 [0.03] vs 1.07 [0.02], p < 0.0001). We divided HIV positive mothers to 4 groups, those with vitamin A concentrations of less than 0.70, between 0.70 and 1.05, between 1.05 and 1.40, and greater than or equal to 1.40 mumol/L. The mother-to-child transmission rates for each group were 32.4%, 26.2%, 16.0%, and 7.2%, respectively (p < 0.0001). Maternal CD4 cell counts, CD4%, and CD4/CD8 ratio were also associated with increased mother-to-child transmission of HIV. Maternal age, body-mass index, and breastfeeding practices were not significantly associated with higher mother-to-child transmission. Our study suggests that maternal vitamin A deficiency contributes to mother-to-child transmission of HIV.

Human Immunodeficiency Virus Load in Breast Milk, Mastitis, and Mother-to-Child Transmission of Human Immunodeficiency Virus Type 1

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.

Trends of HIV-1 and Sexually Transmitted Diseases Among Pregnant and Postpartum Women in Urban Malawi

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.

Effect of cleansing the birth canal with antiseptic solution on maternal and newborn morbidity and mortality in Malawi: clinical trial.

Abstract Objective: To determine if cleansing the birth canal with an antiseptic at delivery reduces infections in mothers and babies postnatally. Design: Clinical trial; two months of no intervention were followed by three months of intervention and a final month of no intervention. Setting: Queen Elizabeth Central Hospital (tertiary care urban hospital), Blantyre, Malawi. Subjects: A total of 6965 women giving birth in a six month period and their 7160 babies. Intervention: Manual wipe of the maternal birth canal with a 0.25% chlorhexidine solution at every vaginal examination before delivery. Babies born during the intervention were also wiped with chlorhexidine. Main outcome measures: Effects of the intervention on neonatal and maternal morbidity and mortality. Results: 3635 women giving birth to 3743 babies were enrolled in the intervention phase and 3330 women giving birth to 3417 babies were enrolled in the non-intervention phase. There were no adverse reactions related to the intervention among the mothers or their children. Among infants born in the intervention phase, overall neonatal admissions were reduced (634/3743 (16.9%) v 661/3417 (19.3%), P<0.01), as were admissions for neonatal sepsis (7.8 v 17.9 per 1000 live births, P<0.0002), overall neonatal mortality (28.6 v 36.9 per 1000 live births, P<0.06), and mortality due to infectious causes (2.4 v 7.3 per 1000 live births, P<0.005). Among mothers receiving the intervention, admissions related to delivery were reduced (29.4 v 40.2 per 1000 deliveries, P<0.02), as were admissions due to postpartum infections (1.7 v 5.1 per 1000 deliveries, P=0.02) and duration of hospitalisation (Wilcoxon P=0.008). Conclusions: Cleansing the birth canal with chlorhexidine reduced early neonatal and maternal postpartum infectious problems. The safety, simplicity, and low cost of the procedure suggest that it should be considered as standard care to lower infant and maternal morbidity and mortality.

HIV infection and disturbances of vaginal flora during pregnancy

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.

Traditional vaginal agents: use and association with HIV infection in Malawian women.

Objectives: To assess the prevalence of traditional vaginal agent use in Malawian women and its association with HIV infection. Methods: Consenting, consecutive antenatal women were administered a questionnaire and screened for sexually transmitted diseases (STD) including HIV. Results: Of the 6603 consenting women, 886 (13%) reported using intravaginal agents for tightening and 2222 (34%) for self‐treatment of vaginal discharge and itching. A higher proportion of HIV‐infected than uninfected women (17% versus 14%) reported use of intravaginal agents for treatment (odds ratio, 1.29; 95% confidence interval, 1.05‐1.57), but no difference in HIV status was found when these agents were used for tightening. In multivariate analysis, vaginal agent use for treatment was independently associated with HIV seropositivity. Conclusions: The association of HIV infection with vaginal agents for self‐treatment, but not for tightening, suggests that STD may play a role or that vaginal agents are used differently for the two purposes. In addition to a small increased risk of HIV infection associated with vaginal agent use, these agents may interfere with condom effectiveness or acceptability of vaginal microbicides.

HIV-1 and pregnant women : Associated factors, prevalence, estimate of incidence and role in fetal wastage in Central Africa

The major goals of this study were to measure the current prevalence and estimate the annual incidence of HIV-1 infection in young pregnant women from urban Malawi, to identify factors that were associated with HIV-1 infection, and to examine adverse pregnancy outcomes. Four hundred and sixty-one consecutive pregnant women were studied when they presented for prenatal care. The overall seroprevalence for HIV-1 infection in these urban populations was 17.6% (81 out of 461) during early 1989. Based on previous seroprevalence in similar unselected pregnant women, the estimated annual incidence of HIV-1 seroconversion in urban pregnant women ranged from 3 to 4% per annum between 1985 and 1987 and from 7 to 13% between 1987 and 1989. HIV-1 infection was significantly associated with reactive syphilis serology. Reported history of sexually transmitted disease was also correlated with HIV-1 infection but was not statistically significant. Other variables, such as history of transfusion, history of tuberculosis, parity or occupation were not associated with HIV-1 infection. History of spontaneous abortion was significantly associated with reactive syphilis serology, HIV-1 infection and history of sexually transmitted disease. In logistic regression analysis, HIV-1 infection remained the only significant variable that was correlated with spontaneous abortion. This study suggests that HIV-1 infection may play a role in fetal wastage.

Mortality after the first year of life among human immunodeficiency virus type 1-infected and uninfected children

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.

Reported condom use is not associated with incidence of sexually transmitted diseases in Malawi.

Objectives:To establish frequency of reported condom use and validate reliability of self-reporting among urban women in Malawi. Design:Cross-sectional survey in antenatal women in 1989 and 1993. Prospective study in cohort first surveyed in 1989. Methods:A total of 6561 women in 1989 and 2460 women in 1993 answered questions about condom use and sexual activity, had a physical examination and were screened for HIV. A subset of women from the 1989 screening were administered a questionnaire and tested for syphilis, Neisseria gonorrhoeae and Trichomonas vaginalis infections every 6 months. Results:Although between the two cross-sectional studies intermittent condom use increased from 6 to 15% (P<0.001) with no difference according to HIV infection, consistent use was reported by less than 1%. In the prospective study, women reported a higher condom use at any visit than either group assessed cross-sectionally. Consistent condom use peaked at 62% in the first 6 months, but declined to as low as 8% in the second year of follow-up. Condom use at each visit, either intermittent or consistent, was higher in HIV-seropositive than HIV-seronegative women. Overall, the incidence of gonorrhea, trichomoniasis and syphilis did not decline in women reporting consistent condom use. Conclusions:In prospectively followed women reports of consistent condom use was substantially higher than in cross-sectional surveys, but rapidly decreased over time, irrespective of HIV status. The presence of new sexually transmitted diseases suggests that this population of urban women overreports condom use or underreports sexual activity, or both. Intensive and sustained education is needed to achieve consistent condom use. Biologic markers of sexual activity are useful in interpreting reported condom use.