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Biomedical subjects

D Moodley

Publications and source records attributed to D Moodley.

At least 37 records · Page 2Linked to original sources
PubMed1999

Mortality in a cohort of children born to HIV-1 infected women from Durban, South Africa.

OBJECTIVES: To describe mortality in a cohort of infants with vertically transmitted HIV-1 infection. PATIENTS AND METHODS: Children of HIV-1 infected women were followed up from birth and a record was made at each visit of growth, development and all illnesses. Details surrounding death were obtained from hospital records. RESULTS: The final cohort comprised 48 infected and 93 uninfected children; there were 25 deaths, 17 of which (35%) were regarded as being HIV-related. The mean age at death of HIV-related cases was 10.1 months (range 1-48 months), with 83% of HIV-related deaths occurring before the age of 10 months. The commonest diagnoses at the time of death were diarrhoea, pneumonia, failure to thrive and severe thrush. These findings, together with neurological abnormalities, often presaged rapid deterioration and death. CONCLUSIONS: Mortality among children with vertically acquired HIV infection is high in the first year of life. Death in these subjects was due to the common causes of morbidity and mortality among all children in developing countries. A combination of diarrhoea, pneumonia, failure to thrive, and neurological abnormalities should alert one to the possibility of rapidly progressive disease and death.

AIDS-Related Opportunistic Infections↗
PubMed1998

The early natural history of vertically transmitted HIV-1 infection in African children from Durban, South Africa.

Forty-eight children with vertically transmitted HIV-1 infection and 93 uninfected infants were followed up at regular intervals from birth for a mean of 26 months. They were examined physically, growth and development were assessed and illnesses recorded. Seventy per cent of infected infants were symptomatic by 6 months. Relative risks in the infected infants were highest for lymphadenopathy (4.56; CI 2.7-7.7), failure to thrive (4.48; 2.57-7.81), and neurological abnormalities (3.32; 1.9-5.58). The most frequent findings were diarrhoea (78%), pneumonia (76%) and lymphadenopathy (70%). Thrush and pneumonia occurred early but declined over time, whereas diarrhoea and neurological abnormalities occurred later and increased in frequency. A diagnosis of AIDS was made in 44% of infected infants by 12 months of age. Mortality in infected infants was 35.4%, and 76% of deaths occurred within the 1st year. About two-thirds of HIV-infected infants survived into early childhood. In South African children with vertically acquired HIV-1 infection the onset of disease is early and deterioration to AIDS and death are rapid. Infected infants can be easily recognized clinically, the majority by 6 months of age.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Pharmacokinetics and antiretroviral activity of lamivudine alone or when coadministered with zidovudine in human immunodeficiency virus type 1-infected pregnant women and their offspring.

The safety, pharmacokinetics, and antiretroviral activity of lamivudine alone and in combination with zidovudine was studied in pregnant women infected with human immunodeficiency virus type 1 (HIV-1) and their neonates. Women received the drugs orally from week 38 of pregnancy to 1 week after delivery. Neonate therapy began 12 h after delivery and continued for 1 week. Both treatment regimens were well-tolerated in women and newborns. Lamivudine and zidovudine pharmacokinetics in pregnant women were similar to those in nonpregnant adults. Lamivudine and zidovudine freely crossed the placenta and were secreted in breast milk. Neonatal lamivudine clearance was about half that in pediatric patients; zidovudine clearance was consistent with previous reports. HIV-1 RNA could be quantified in 17 of the 20 women. At the onset of labor/delivery, mean virus load had decreased by approximately 1.5 log10 copies/mL in both treatment cohorts. Although not definitive for HIV-1 infection status, all neonates had HIV-1 RNA levels below the limit of quantification at birth and at ages 1 and 2 weeks.

Administration, Oral↗
PubMed1997

Age-related pattern of immunoglobulins G, A and M in children born to HIV-seropositive women.

In a cohort of 56 children born to HIV-seropositive African women, 19 met the criteria for HIV-infected children and 37 remained antibody-negative at 18 months of age. Blood samples taken at birth and 3-monthly until 18 months of age were processed and analysed by laser nephelometry for serum immunoglobulin (IgG, IgA and IgM) levels. In the infected group of children. higher levels of IgG were observed during their 1st 18 months of life reaching statistical significance at 3, 6, 15 and 18 months. Higher levels of IgA at 3 months and at 15 and 18 months, and higher levels of IgM at 3 months and 18 months later were statistically significant. All four infected children who died before the age of 6 months showed signs of hypergammaglobulinaemia (IgG and IgA) by 3 months of age. In this study the earliest and most common immunological abnormality was hypergammaglobulinaemia and infected infants with higher morbidity and mortality had more evident immunoglobulin abnormalities than infected children who survived. However, the immunological abnormalities in this small cohort did not precede the onset of severe symptoms and cannot therefore be used to predict clinical outcome.

Age Factors↗
PubMed1997

The relationship between maternal-infant antibody levels and vertical transmission of HIV-1 infection.

This study assesses the predictive value of the ratio of HIV-1 antibodies in the newborn at birth to that in the mother for perinatally transmitted infection confirmed subsequently by age 18 months. The ratio of HIV-1 (EIA) antibody levels in the baby at birth to that in the seropositive mother after the first trimester (sequenstration index SI) was available in 114 of a perinatal cohort of 137 infants. We related this ratio to the HIV infection status of the children by 18 months, HIV-1 DNA PCR and HIV-specific IgA antibody detection at birth, between 3 and 6 months, and morbidity and mortality. Thirty-five of the 137 (26 per cent) children were diagnosed as infected by 18 months. The mean (SD) HIV SI was 1.57 (0.88) in 29 infected and 0.83 (0.42) in 85 uninfected infants (P < 0.0001). Sensitivity and specificity of a threshold SI of 1.27 (mean +/- 2 SD of uninfected group) for the prediction of perinatal HIV-1 infection were 41 and 98 per cent, respectively. The reason for the higher SI in the infected babies is the combination of lower antibody titres in the transmitting mothers with raised levels in the infected babies. A similar analysis of antibody ratios showed no statistical differences for measles and tetanus (P > 0.1) between HIV infected and uninfected groups. There was a tendency to increased morbidity (Pearson's correlation coefficient r = 0.31) and more severe disease in those with higher HIV-1 SI. Three of 17 (18 per cent) peripheral blood samples from infected children at birth were PCR positive; all had SI's above the threshold. Overall sensitivity and specificity of PCR were 85 per cent each. Eleven of the 29 infected children were HIV-1 specific IgA positive at birth; six (64 per cent) of these had an SI > 1.27. This simple SI of HIV-1 EIA antibodies at birth is comparable to elaborate techniques in its power to predict perinatally acquired infection. It may be a cheap, reliable and rapid screening test for vertically transmitted HIV-1 infection.

Adolescent↗
PubMed1997

HIV-1 specific immunoglobulin A antibodies as an effective marker of perinatal infection in developing countries.

HIV-1 specific IgA antibody testing using commercially available reagents was evaluated at birth to 15 months in a group of infants born to HIV-seropositive South African women. Following IgG depletion of serum samples, 33/35 (94 per cent) of the infected infants and 3/99 (3 per cent) of the uninfected infants showed positive IgA reactivity. Sensitivity at birth was 24 per cent and improved with age; 82 per cent at 3 months, 87 per cent at 6 months and 94 per cent at 12 months. The overall positive and negative predictive values were 92 and 98 per cent, respectively. An evaluation of IgA and PCR in a subsample of infants indicated a better sensitivity of PCR within 3 months of birth, but IgA detection offered a higher overall sensitivity (87 v. 83 per cent) and specificity (91 v. 85 per cent). No significant difference in IgA level was observed between transmitting mothers and non-transmitting mothers. A moderate correlation existed between IgA level in the infant and the cumulative morbidity score, however a stronger association was observed between high IgA levels in the infected infant and rapid disease progression. The viral specific IgA assay is a simple, reliable and cost-effective diagnostic and prognostic test for perinatal HIV infection in developing countries.

Biomarkers↗
PubMed1997

Breastfeeding by HIV-1-infected women and outcome in their infants: a cohort study from Durban, South Africa.

BACKGROUND: Women in developing countries have the difficult choice of balancing the risk of transmitting HIV through breast milk against the substantial benefits of breastfeeding. It is not known, however, whether the benefits of breastfeeding are the same when the mother is HIV-infected. Therefore, we examined the impact of breastfeeding on infections, growth and mortality in the infants of HIV-1-infected women. METHODS: Infants of HIV-1-positive women were followed from birth and at each visit they were examined, growth parameters were recorded and notes were made of feeding method, and of current and interim illnesses. RESULTS: Of the 43 HIV-infected and 90 non-infected infants for whom feeding data were available, 36 infants (27%) were exclusively breastfed, 76 (57%) received mixed feeding, and 21 (16%) received formula only. The HIV transmission rate was 39% in those exclusively breastfed, 24% in those fed exclusively on formula and 32% in those receiving mixed feeding [relative risk (RR), 7.39; 95% confidence interval (CI), 1.67-32.6 between the exclusive breast and formula only groups]. There was a stepwise increase in the transmission rate with duration of exclusive breastfeeding of 1, 2 and 3 months (45%, 64%, and 75%, respectively). Of the infected infants, seven (50%) exclusively breastfed, 13 (51%) of those on mixed feeds and none on formula only developed AIDS; exclusively breastfed infants had a slower rate of progression to AIDS (mean age, 7.5 months versus 5.0 months, P = 0.2242) than those on mixed feeds. Mortality (which occurred in the infected infants only) was 19% in the exclusively breastfed infants; 13% in those on mixed feeds and 0% in those exclusively formula-fed. The frequency of failure to thrive and episodes of diarrhoea and pneumonia were not significantly different between the three groups in both the infected and non-infected infants. CONCLUSIONS: Exclusive breastfeeding by HIV-infected women does not appear to protect their infants against common childhood illnesses and failure to thrive, nor does it significantly delay progression to AIDS. The implication of the trend towards differential mortality rates according to feeding groups is uncertain and requires further investigation.

Breast Feeding↗
PubMed1997

Lymphocyte subset changes between 3 and 15 months of age in infants born to HIV-seropositive women in South Africa.

The evolution of T-lymphocyte subsets during infancy in perinatally HIV-infected African babies has not been previously described. In a hospital-based cohort study, T-lymphocyte subset changes were investigated in 72 South African black children born to HIV seropositive mothers. Sixteen (22.2%; children were classified as infected and 56 (77.8%) as uninfected by 18 months of age. Four (25%) of the infected infants died before the age of 9 months from HIV-related disease. The CD4 and CD8 T-lymphocyte subsets, expressed in absolute numbers, as percentages, percentiles or as ratios, were clear indicators of HIV infection at all ages between 3 and 15 months. The most marked changes were a decreased percentage of CD4 cells and an increase in percentage of CD8 cells in the infected group. In the 4 infected infants who died, CD8 count and CD4:CD8 ratio clearly predicted poor clinical outcome at 3 months. Taken together, both CD4:CD8 ratio and CD4 percentage are reliable markers of HIV infection in an African paediatric population; however, a raised CD8 lymphocyte count rather than a CD4 count is a more specific prognostic marker of disease progression in HIV infected children.

Age Factors↗
PubMed1996

Cesarean deliveries and maternal-infant HIV transmission: results from a prospective study in South Africa.

Data from a prospective study undertaken at an urban hospital in Durban, South Africa, were used to investigate associations between maternal-infant HIV transmission, mode of delivery, and specific circumstances of cesarean deliveries. A total of 141 children of HIV-infected women were followed until the children were 15 months of age to determine their HIV status. supplementary data were collected from obstetric records, masked to the HIV status of the children. In this African and predominantly breast-fed population, infants delivered vaginally were more likely to be infected (39.8% infected) than were infants delivered by cesarean section [22.9% infected; odds ratio (OR), 0.45; 95% confidence interval (CI), 0.20-0.99]. There were no significant differences between cesarean deliveries undertaken following prior rupture of membranes and those undertaken with membranes intact, but numbers for this comparison were small. Singleton cesarean deliveries without concurrent obstetric complications had lower rates of transmission than did vaginal deliveries (OR, 0.20; 95% CI, 0.04-0.94). These results suggest that certain intrapartum events may modify the risk of HIV transmission and highlight the importance of collecting more detailed intrapartum information in order to clarify the route by which mode of delivery may be associated with maternal-infant HIV transmission.

Breast Feeding↗
PubMed1996

beta 2-Microglobulin and CD4/CD8 ratio as HIV-1 markers of maternal transmissibility, neonatal infection and disease progression.

A hospital-based cohort study assessing the function of surrogate markers (beta 2-microglobulin and CD4/CD8 ratio) in predicting maternal HIV transmissibility and disease progression in infants was conducted in 110 seropositive black South African mother-infant pairs. There were no differences in beta 2-microglobulin (beta 2-M) levels between the 27 transmitting and 83 non-transmitting mothers (P = 36). beta 2-M levels were higher in the infected that in the uninfected infants, but were significantly higher at 1 month (P = 0.04) and again at 12 months (0.03). A CD4/CD8 ratio < 1 was increasingly reported in the infected infants from 3 months (60.9%) to 15 months (93.8%) of age, and in three (5.4%) uninfected infants. Of the eight infected infants who rapidly progressed to death by 9 months, increased beta 2-M levels at birth and 1 month and inverted CD4/CD8 ratios at 3 months were strongly associated with the objective morbidity score. However, the CD4/CD8 ratio (positive predictive value 82.4%, negative predictive value 82.8%) at 3 months or later remained a better indicator of disease progression than beta 2-M (positive predictive value 33.3%, negative predictive value 74.4%).

Adolescent↗
PubMed1996

Use of HIV-1 specific immunoglobulin G3 as a serological marker of vertical transmission.

The objective of the study was to indicate HIV infection in infants. The patients were part of a longitudinal cohort of 43 infants born to HIV seropositive mothers. A modified Genelavia EIA primarily directed against HIV envelope proteins was used. An alkaline phosphatase labelled IgG3 conjugate was substituted in place of the kit conjugate. HIV specific IgG3 clearance was optimal at 6 months, whilst HIV total antibody was reliable only from age 12 months onwards. At 6 months no detectable IgG3 were found in 91 per cent of uninfected infants where more of these infants had reduced their total HIV antibody titres at the same period. We confirm that HIV specific IgG3 measurement is a reliable and cost effective means of identifying HIV infected infants from 6 months of age onwards.

Biomarkers↗
PubMed1996

Determinants of mother-to-child transmission of human immunodeficiency virus type 1 infection in a cohort from Durban, South Africa.

OBJECTIVES: To determine the vertical transmission rate of HIV-1 infection and to assess the influence of maternal risk factors on transmission in infants born to HIV-1-infected black women in Durban. DESIGN: A prospective, hospital-based cohort study conducted at King Edward VIII hospital, Durban. HIV-1-seropositive women were enrolled into the study, and their infants were followed up at regular intervals from birth to early childhood. The infection status of the children was classified and the transmission rate was computed according to the recommendations of the workshop held in Ghent, Belgium (1992). RESULTS: The final cohort of 181 infants were classified as 48 infected, 93 not infected and 40 indeterminate. Clearance of maternal antibodies was achieved by 12 months of age in virtually all infants who became seronegative. The intermediate transmission rate was 34% (95% confidence interval, 26 to 42). Deliveries by cesarean section had significantly lower transmission (relative risk, 0.46; 95% confidence interval 0.23 to 0.91). Women with lower hemoglobin concentrations during pregnancy (< 10 g/dl) had an increased risk of transmission (relative risk, 1.99; 95% confidence interval, 1.18 to 3.34). Advanced maternal age, multiparity, positive syphilis serology, duration of ruptured membranes, preterm delivery and breast-feeding were not associated with an increased risk of transmission. CONCLUSIONS: This study, the first from South Africa, has confirmed that the rate of vertical transmission of HIV-1 is as high as that reported from most African cohorts. Cesarean sections were protective against transmission, whereas low hemoglobin values values were associated with an increased risk of transmission. Twelve months could be used as the cutoff age for teh diagnosis of vertical infection using antibody tests.

Age of Onset↗