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.

Does umbilical cord blood polymerase chain reaction positivity indicate in utero (pre-labor) HIV infection?

OBJECTIVE: To compare risk factors for infants whose cord blood was positive for HIV DNA with those who were cord blood-negative but found to be HIV DNA-positive in early infancy. METHODS: In 1994, infants born to HIV-infected women were enrolled in a study in Blantyre, Malawi. Birth weight and transmission risk factors from cord blood-positive infants were compared with cord blood-negative/HIV-positive infants on their first postnatal visit (4-7 weeks of age). Testing for HIV DNA on cord and peripheral blood was performed by polymerase chain reaction. RESULTS: Of 249 HIV-infected infants (overall transmission rate, 26%), 83 (33%) were cord blood-positive and 166 were initially cord blood-negative. The mean birth weight was 2.1% (59 g) lighter in cord blood-positive infants than initially cord blood-negative infants; initially cord blood-negative infants were 2.8% (80 g) lighter than uninfected infants born to HIV-infected women. There were no significant differences in the risk factors for infection between HIV-infected cord blood-positive and -negative infants; when transmission was increased, both HIV-infected cord blood-positive and -negative infants contributed to the increase in a similar proportion. INTERPRETATION: It was concluded that umbilical cord blood positivity for HIV DNA did not identity a subset of in utero HIV-infected infants and suggested that HIV-infected cord blood-positive and -negative infants have similar timing and routes of 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.

PIP: An exploratory study was conducted in Malawi to determine whether a correlation exists between human immunodeficiency virus (HIV) and traditional practices involving the intravaginal application of substances such as herbs and pulverized stone. Included in the survey were 6603 consecutive consenting volunteers who presented at the prenatal clinic of an urban hospital from October 1989-October 1990. The median age of study participants was 24 years. Although only 11% reported having had a sexually transmitted disease (STD) in the three years preceding the interview, laboratory analysis revealed the presence of such an infection in 46%. HIV infection was found in 1502 (23%). A total of 2953 (45%) of these pregnant women reported use of vaginal agents or vaginal incision, either for the treatment of discharge or itching or for the enhancement of sexual pleasure through vaginal tightening. Concerns have been raised that the placement of desiccants, irritants, and astringents in the vagina can induce certain physiological changes that increase the risk of HIV infection. Demonstrated in this survey was a slight association between HIV seropositivity and the use of vaginal agents for self-medication but not for vaginal tightening. In the univariate analysis, this finding persisted only for pregnant women without past or current STD infection. In the multivariate analysis, users of vaginal agents for treatment had a small increased risk of HIV in addition to--and independently of--the risk conferred by an STD history. It is possible, however, that the use of vaginal agents for self-medication is a marker for the presence of genital tract inflammation--a co-factor for HIV transmission. Given the extent of this traditional practice and its potential risk, more research is urged on the type of vaginal agents used and their effects on vaginal tissue.

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.

PIP: To determine the frequency of reported condom use and validate the reliability of self-reporting among urban women in Malawi, 6561 women in 1989 and 2460 women in 1993 answered survey 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, gonorrhea, and Trichomonas vaginalis infections every six months. The study populations consisted of consecutive women presenting for their first antenatal visit to Queen Elizabeth Hospital in Blantyre, Malawi. Intermittent condom use increased from 6% to 15% between the two cross-sectional studies, with no difference according to HIV infection; consistent condom use was reported by less than 1%. In the prospective study, women reported higher condom use at any visit than either group assessed cross-sectionally. Consistent condom use peaked at 62% in the first six months, but declined to as low as 8% during the second year of follow-up. Condom use at each visit, either intermittent or consistent, was higher among HIV-seropositive than HIV-seronegative women. Overall, the incidence of syphilis, gonorrhea, and trichomoniasis did not decline in women reporting consistent condom use. This incidence of new sexually transmitted diseases suggests that the studied population either overreports condom use or underreports sexual activity, or both.

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.

PIP: Prevalence rates of HIV-1 and other sexually transmitted diseases (STDs) among pregnant and postpartum women were investigated in sequential, cross-sectional studies (1990, 1993, and 1994-95) conducted at Queen Elizabeth Central Hospital in Blantyre, Malawi. Annual anonymous, unlinked testing revealed a linear increase in HIV-1 prevalence among antenatal patients from 2.0% in 1985 to 32.8% in 1996. Analysis of demographic attributes of women enrolled in the 1990 and 1993 surveys of consecutive, first-visit antenatal women (n = 6603 and 2161, respectively) and the 1994-95 study of all women giving birth at the hospital during a 6-month period (n = 6964) indicated that HIV-infected women were most likely to be young, with fewer pregnancies, and be more educated. The highest age-specific HIV prevalence shifted from 20-24 years in 1990 to 30-34 years in 1996, indicating an aging cohort of women who became infected at a younger age. Reported lifetime use of condoms increased from 5.6% in 1990 to 17.5% in 1993, then declined to 4.9% in 1995; condom use was consistently higher among HIV-positive than HIV-negative women. The prevalence of all STDs (syphilis, trichomoniasis, gonorrhea, and genital warts and ulcers) declined significantly during 1990-96, with the most consistent decreases recorded among HIV-positive women. In a follow-up study of 1173 HIV-seronegative, postpartum women evaluated for 2302 person-years (average duration, 30.9 months), 97 seroconverted (4.21/100 person-years). The seroconversion rate declined steadily from 21.26/100 person-years in 1990 to 1.11/100 person-years in 1994-95. These findings are consistent with those from other sub-Saharan African countries, indicating a rapid increase in HIV prevalence followed by stabilization within about 10 years of the onset of the epidemic. The large decline in STD prevalence in the antenatal population suggests that Malawi's national AIDS prevention program is having an impact, either through improved STD diagnosis and treatment or reduced risk behaviors.

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.

Association of HIV-1 load and CD4 lymphocyte count with mortality among untreated African children over one year of age.

OBJECTIVE: To examine the association of viral load and CD4 lymphocyte count with mortality among HIV-infected children over one year of age. DESIGN: A 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). METHODS: Morbidity 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. RESULTS: Of 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 (> or = 250,000 copies/ml median value) had the worst survival; children with high CD4 cell counts (> or = 15%) and low viral loads (< 250,000 copies/ml) had the best survival. CONCLUSION: As 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.

V3 loops of HIV-1 specimens from pregnant women in Malawi uniformly lack a potential N-linked glycosylation site.

PIP: The HIV-1 env gene was amplified from the peripheral blood mononuclear cells of 14 infected pregnant women in Malawi. Nested polymerase chain reaction (PCR) and DNA sequencing were performed. The PCR product was purified and the C2-V3 region sequenced. Using the similarity function of the multiple aligned sequence editor, 13 of the nucleotide sequences were compared. The interperson variation, based on single base substitutions, ranged from 7.3 to 22.2% (mean 13.6%). All of the sequences showed the tetrapeptide motif at the crown of the V3 loop which is commonly seen among HIV-1 subtypes A, C, D, and E. The C2-V3 coding sequences clustered with the subtype C sequence reported from South Africa. In addition, all of these sequences lacked a potential N-linked glycosylation site found in all HIV-1 sequences except subtype C. In these specimens, the predominant replacement was valine. The role of this site in HIV-1 transmission is controversial.^ieng

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.

A retrospective study of childhood mortality and spontaneous abortion in HIV-1 infected women in urban Malawi.

HIV infection in pregnant women has been shown to have an adverse effect on the fetus and newborn. We undertook this study to examine the adverse effect of maternal HIV-1 infection on two outcomes of the previous pregnancy, as reported by the women: childhood mortality under the age of 3 years and spontaneous abortion. Some 6605 consecutive women who presented to a large urban hospital in Malawi for antenatal care were interviewed and tested for HIV-1 antibody. Of these 4229 (64%) were multiparous and 833 (19.7%) were seropositive for HIV-1. A history of under-3 mortality of the previous pregnancy was more common in HIV-1 seropositive than HIV-1 seronegative women (35% versus 15%, P less than 0.001). In the previous pregnancy, death of infants and children under 3 years was 77 and 119 per 1000 respectively for HIV-1 seronegative mothers, but increased to 171 and 292 per 1000 in infants and children under 3 years for HIV-1 seropositive mothers. History of child mortality was independently associated with positive HIV-1 serology, positive syphilis serology, low socioeconomic status, young age and not having married. There was no correlation between history of child mortality and reported symptoms of HIV/AIDS by infected mothers, except for history of tuberculosis which was reported more often by mothers whose child had died (4% versus 1%, P less than 0.036).(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of human immunodeficiency virus infection on birthweight, and infant and child mortality in urban Malawi.

BACKGROUND: Low birthweight, prematurity and intra-uterine growth retardation (IUGR) are major determinants of child survival. Therefore, it is important to assess excess mortality due to human immunodeficiency virus (HIV) infection in populations where low birthweight is common. METHODS: A prospective study was conducted on 1385 children born to seropositive and seronegative women in urban Malawi. Children were regularly examined and tested for HIV. RESULTS: The mortality rate of children of HIV seropositive mothers was substantially higher (223/1000 at 12 months, 317/1000 at 24 months and 360/1000 at 30 months) than that of children of seronegative mothers (68/1000 at 12 months, 106/1000 at 24 months and 118/1000 at 30 months). The incidence of prematurity and IUGR was also higher in infants of HIV seropositive mothers than in infants of seronegative mothers (12.7% versus 3.8%, P < 0.001 for premature and 7.7% versus 4.4%, P = 0.02 for IUGR infants). The mother-to-infant HIV-1 transmission rate was 35.1%. After 12 months of age, HIV infected children showed the highest mortality; however, uninfected children of HIV seropositive and children of HIV seronegative mothers had similar mortality. The mean birthweight of HIV infected and uninfected children was not significantly different. In HIV infected children the most frequent causes of death were diarrhoea, pneumonia and failure to thrive. Less common risk factors for child mortality included active maternal syphilis and cervicitis/vaginitis. CONCLUSION: The substantial difference in survival among children of HIV infected and uninfected mothers suggests that mortality could be reduced if HIV infection were not a risk factor. To decrease childhood mortality, a combination of interventions such as treatment of sexually transmitted infections during pregnancy and measures to reduce mother-to-infant transmission should be adopted.

PIP: Low birth weight, prematurity, and intra-uterine growth retardation (IUGR) are major determinants of child survival. Therefore, it is important to assess excess mortality due to human immunodeficiency virus (HIV) infection in populations where low birth weight is common. A prospective study was conducted on a total of 1385 children born to 679 HIV-seropositive and 687 seronegative women in urban Malawi. Children were regularly examined and tested for HIV. The mortality rate of children of HIV-seropositive mothers was substantiality higher (223/1000 at 12 months, 317/1000 at 24 months, and 360/1000 at 30 months, p 0.0001) than that of children of seronegative mothers (68/1000 at 12 months, 106/1000 at 24 months, and 118/1000 at 30 months). The incidence of prematurity and IUGR was also higher in infants of HIV-seropositive mothers than in infants of seronegative mothers (12.5% versus 3.8%, p 0.001 for premature and 7.7% versus 4.4%, p = 0.02 for IUGR infants). The mother-to-infant HIV-1 transmission rate was 35.1%. The overall incidence of low birth weight was 14.1%, but the incidence was 20.1% among children of seropositive mothers and 8.3% among those of seronegative mothers (p 0.001). After 12 months of age, HIV-infected children showed the highest mortality; however, uninfected children of HIV-seropositive and children of HIV-seronegative mothers had similar mortality. The mean birth weight of HIV-infected and uninfected children was not significantly different. In HIV-infected children the most frequent causes of death were diarrhea, pneumonia, and failure to thrive. Less common risk factors for child mortality included active maternal syphilis and cervicitis/vaginitis. A possible enrolment bias could have resulted in lower mortality estimates among babies of HIV-seronegative mothers. To decrease childhood mortality, a combination of interventions such as treatment of sexually transmitted infections during pregnancy and measures to reduce mother-to-infant transmission should be adopted.

Childhood malaria parasitaemia and human immunodeficiency virus infection in Malawi.

PIP: Malaria and human immunodeficiency virus (HIV) infection are major health problems in many areas in Sub-Saharan Africa. An interaction between malaria and HIV infection has been postulated, since both produce similar cellular immune responses, with a lowering of the CD4/CD8 lymphocyte ratio. The frequency of malaria parasitemia was examined in children born to HIV-seropositive and seronegative mothers attending regular postnatal visits. A prospective study on mother-to-infant transmission of HIV had been underway since 1989 in Queen Elizabeth Central Hospital, Blantyre, a major hospital in urban Malawi. Standard HIV serology was performed on pregnant women, after obtaining consent. To reduce the effect of selection bias and seasonality, HIV seropositive (case) and seronegative (control) mothers and their infants were enrolled at delivery. Children included in the study were 503 born to 494 HIV-seropositive mothers and 540 born to 536 HIV-seronegative mothers. At each 3-monthly postpartum visit a Giemsa-stained thick blood film from the child was examined for malaria parasites. Children born to HIV-seropositive mothers were tested for HIV antibodies at 12 and 18 months of age. Of the 353 children born to HIV-seropositive mothers, 82 children (23.2%) were found to be HIV seropositive by enzyme-linked immunosorbent assay and Western blotting at 12 and 18 months. No statistically significant difference was found in frequency of malaria parasitemia by maternal or infant HIV serostatus after controlling for child's age. There was, however, a significant trend of increase in high parasitemia with age, irrespective of the HIV serostatus of the mother or the child. The frequency of parasitemia was higher in the wet season than in the dry season. This study suggests that maternal or infant HIV infection does not alter susceptibility to, or the clinical course of, malaria in infants.^ieng

Assessment of iron status using plasma transferrin receptor in pregnant women with and without human immunodeficiency virus infection in Malawi.

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, alpha1-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 microg/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.

Plasma and breast milk vitamin A as indicators of vitamin A status in pregnant women.

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.

Mastitis and immunological factors in breast milk of human immunodeficiency virus-infected women.

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.

Carotenoid status of pregnant women with and without HIV infection in Malawi.

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.

An intervention to reduce the risk of mother-to-infant HIV transmission: results of a pilot toxicity study.

Although unproven, vaginal cleansing with antiseptics during labour could be a practical approach to reducing the rate of transmission of HIV infection from mother to infant. Before initiating a large scale clinical trial of the antiseptic chlorhexidine, we conducted a study to assess possible toxic effects as well as beneficial outcomes in 160 women volunteers: 40 non-pregnant chlorhexidine washed, 40 pregnant not washed, 40 pregnant saline washed, and 40 pregnant chlorhexidine washed. The wash was easily administered by the nurse-midwives. The participants generally felt better after the procedure, and had no complaints or adverse reactions in the subsequent 24 hours. Bacteriologically, the procedures lowered the carriage of Group B streptococcus and Staphylococcus aureus, but did not affect the frequency of T. vaginalis detection. No clinical problems were seen, and therefore the larger clinical trial of efficacy will proceed. Results of this trial are expected in late 1995.

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

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.

PIP: A clinical trial of the effects of cleansing both the birth canal and the newborn with an antiseptic indicates that this simple procedure substantially reduces early neonatal and maternal postpartum infection. The antiseptic used, a 0.25% chlorhexidene solution, has been shown to reduce neonatal morbidity due to group B streptococcus and can neutralize HIV. Enrolled in the study were 6965 women giving birth to 7160 infants at Queen Elizabeth Central Hospital in Blantyre, Malawi, in a 6-month period in 1994. 2 months of no intervention were followed by 3 months of intervention and a final month of no intervention. Significant differences were recorded between the 3743 infants delivered during the intervention phase and the 3417 controls in terms of overall neonatal admissions (16.9 vs. 19.3/1000 live births), admissions for neonatal sepsis (7.8 vs. 17.9/1000 live births), overall neonatal mortality (28.6 vs. 36.9/1000 live births), and mortality due to infectious causes (2.4 vs. 7.3/1000 live births). Significant differences also were found between the 3635 mothers in the intervention group and the 3330 controls in delivery-related admissions (29.4 vs. 40.2/1000 deliveries), admissions due to postpartum infection (1.7 vs. 5.1/1000 deliveries), and the average duration of hospitalization (48.7 vs. 50.2 hours). The cleansing procedure was easily administered, required almost no extra staff time, and cost less than US $0.10 per patient, making it appropriate for standard care.