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Biomedical subjects

H M Coovadia

Publications and source records attributed to H M Coovadia.

At least 37 records · Page 2Linked to original sources
PubMed2001

Variation in breastmilk HIV-1 viral load in left and right breasts during the first 3 months of lactation.

The mechanism and risk factors associated with mother-to-child transmission of HIV-1 through breastfeeding remain unclear; breastmilk viral load may be an important determinant of transmission. Analysis of breastmilk cell-free viral load in samples taken from each breast at 1, 6 and 14 weeks postpartum showed that HIV-1 is shed intermittently and load may differ considerably between breasts of an individual woman at any given time. Breastmilk HIV-1 load was undetectable in approximately one-third of samples.

Breast↗
PubMed2001

Method of feeding and transmission of HIV-1 from mothers to children by 15 months of age: prospective cohort study from Durban, South Africa.

OBJECTIVE: To determine the risk of HIV transmission by infant feeding modality. DESIGN AND SETTING: A prospective study in two hospitals in Durban, South Africa. PARTICIPANTS: A total of 551 HIV-infected pregnant women enrolled in a randomized trial of vitamin A. INTERVENTIONS: Women self-selected to breastfeed or formula feed after being counselled. Breastfeeders were encouraged to practice exclusive breastfeeding for 3-6 months. MAIN OUTCOME MEASURES: Cumulative probabilities of detecting HIV over time were estimated using Kaplan-Meier methods and were compared in three groups: 157 formula-fed (never breastfed); 118 exclusively breastfed for 3 months or more; and 276 mixed breastfed. RESULTS: The three feeding groups did not differ in any risk factors for transmission, and the probability of detecting HIV at birth was similar. Cumulative probabilities of HIV detection remained similar among never and exclusive breastfeeders up to 6 months: 0.194 (95% CI 0.136-0.260) and 0.194 (95% CI 0.125-0.274), respectively, whereas the probabilities among mixed breastfeeders soon surpassed both groups reaching 0.261 (95% CI 0.205-0.319) by 6 months. By 15 months, the cumulative probability of HIV infection remained lower among those who exclusively breastfed for 3 months or more than among other breastfeeders (0.247 versus 0.359). CONCLUSION: Infants exclusively breastfed for 3 months or more had no excess risk of HIV infection over 6 months than those never breastfed. These findings, if confirmed elsewhere, can influence public health policies on feeding choices available to HIV-infected mothers in developing countries.

Breast Feeding↗
PubMed2001

Secretory leukocyte protease inhibitor in vaginal fluids and perinatal human immunodeficiency virus type 1 transmission.

The presence of both viral particles and antiviral mucosal proteins may represent critical determinants of perinatal human immunodeficiency virus type 1 (HIV-1) transmission. In 60 HIV-1-infected women, concentrations of the innate mucosal protein, secretory leukocyte protease inhibitor (SLPI), were lower in vaginal fluid samples from 17 women whose babies became infected than in samples from nontransmitting women (mean+/-SE, 57+/-11 vs. 557+/-177 ng/mL, respectively; P=.01). Rates of transmission among women with higher SLPI concentrations (>100 ng/mL) were lower than those among women with lower concentrations (<100 ng/mL; 8.7% vs. 40.5%, respectively; P=.01). Concentrations of other putative HIV-1-inhibitory innate immune factors were similar in both groups. Concentrations of vaginal HIV-1 tended to be higher in transmitting than in nontransmitting women (407 vs. 174 virions/mL; P=.09). Increased concentrations of selected innate mucosal immune factors, such as SLPI, seem to be associated with reduced rates of perinatal HIV-1 transmission and may contribute to natural antiretroviral defense.

CD4 Lymphocyte Count↗
PubMed2001

T-helper cell responses to HIV envelope peptides in cord blood: protection against intrapartum and breast-feeding transmission.

BACKGROUND: Acquired HIV-specific cell-mediated immune responses have been observed in exposed-uninfected individuals, and it has been inferred, but not demonstrated, that these responses constitute a part of natural protective immunity to HIV. This inference was tested prospectively in the natural exposure setting of maternal-infant HIV transmission in a predominantly breast-fed population. METHODS: Cord blood from infants of HIV-seropositive women in Durban, South Africa, were tested for in vitro reactivity to a cocktail of HIV envelope peptides (Env) using a bioassay measuring interleukin-2 production in a murine cell line. Infants were followed with repeat HIV RNA tests up to 18 months of age to establish which ones acquired HIV-infection. RESULTS: T-helper cell responses to Env were detected in 33 out of 86 (38%) cord blood samples from infants of HIV-seropositive women and in none of nine samples from seronegative women (P = 0.02). Among infants of HIV-seropositive mothers, three out of 33 with T-helper responses to Env were already infected before delivery (HIV RNA positive on the day of birth), two were lost to follow-up, and none of the others (out of 28) were found to be HIV infected on subsequent tests. In comparison, six out of 53 infants unresponsive to Env were infected before delivery, and eight out of 47 (17%) of the others were found to have acquired HIV infection intrapartum or post-partum through breast-feeding (P = 0.02). CONCLUSIONS: T-helper cell responses to HIV envelope peptides were detected in more than one-third of newborns of HIV-infected women; no new infections were acquired by these infants at the time of delivery or post-natally through breast-feeding if these T-helper cell responses were detected in cord blood.

Animals↗
PubMed2001

Characterization of proteinuria in asymptomatic family members and household contacts of children with hepatitis B virus-associated membranous nephropathy.

The biosocial background in which the hepatitis B virus (HBV) carrier state with membranous nephropathy (MN) develops was studied by evaluating HBV carriage and proteinuria among 195 family members and household contacts of 31 index HBV carrier children with MN. Unrelated individuals from the communities of these index cases who were negative for HBV served as controls (n = 123). HBV was determined by using third-generation enzyme-linked immunosorbent assay, slot-blot hybridization, and nested polymerase chain reaction. Patterns of proteinuria were determined by using sodium dodecyl sulfate-polyacrylamide gel electrophoresis; immunoglobulin G and haptoglobulin were suggestive of MN. Seventy-two members (36.9%) of the study group (n = 195) were HBV carriers; 21 of these carriers (29.2%) had proteinuria. Twenty-eight members (41.2%) of the study group who were HBV negative (n = 68) and 26.8% of the controls showed proteinuria. This lack of association between HBV carriage and proteinuria remained when controlled for sex and family relationship. HBV was not protective against the development of proteinuria. Proteinuria suggestive of MN was strongly associated with an abnormal protein-creatinine ratio (P: = 0.001), but was not significantly different between subjects and controls (8.7% versus 6.5%; P: = 0.5). Genetic influences or environmental exposures in these subjects may be responsible for the proteinuria, suggesting underlying glomerular basement membrane damage. Discordance between the HBV carrier state and patterns of proteinuria in the study group suggest that HBV and MN may not be causally related or may reflect exceptional interaction between specifically vulnerable individuals and HBV.

Adolescent↗
PubMed2001

Epidemiology of helminth infections: implications for parasite control programmes, a South African perspective.

OBJECTIVES: To determine the epidemiology of helminthic infections and the efficacy of parasite treatment among rural South African primary school children in the province of KwaZulu-Natal. To assess the South African government's parasite control policy. METHODS: The study recruited 268 school children, aged 8 to 10, and randomly allocated them into treatment and placebo groups (treatment consisted of a single dose of albendazole (400 mg) and praziquantel (40 mg/kg)). Anthropometric measurements and the prevalence and intensity of helminth infections were taken at baseline (prior to treatment) and 16 weeks post treatment. Two weeks after treatment prevalence and intensity were again measured for an approximate 50% sub-sample of the children to investigate efficacy of treatment. An analysis of the South African government's policies concerning parasite control is assessed in the light of these epidemiological findings. RESULTS: Low levels of both stunting and wasting were observed throughout the study (approximately 10% and 1%, respectively), but did not vary significantly across either treatment group or time period (P >0.50). At baseline the observed prevalences for the three main helminths found in this study among the treated children were Ascaris lumbricoides 29.5%, Trichuris trichiura 51.9% and Schistosoma haematobium 22.3%. These prevalences declined significantly to 4.7% (P <0.0005), 38.0% (P < 0.03), and 3.3% (P < 0.0002), respectively, 16 weeks post treatment. The majority of infections observed at baseline were of light intensity, namely A. lumbricoides (50%), T. trichiura (80%) and S. haematobium (100%), and following treatment these levels were reduced significantly (P <0.0001, P< 0.05 and P < 0.005, respectively). The levels of both prevalence and intensity in the untreated group remained constant. The cure rates over the first two weeks of the study were found to be 94.4% for A. lumbricoides, 40% for T. trichiura and 72.2% for S. haematobium. CONCLUSION: The benefits of targeted, school-based treatment in reducing the prevalence and intensity of infection supports the South African government's focus of using school-based interventions as part of an integrated parasite control programme. These strategies and programmes are consistent with recommendations of the World Health Organization (WHO) and The United Nations Children's Fund (UNICEF).

Albendazole↗
PubMed2001

A randomized controlled trial of the effect of antihelminthic treatment and micronutrient fortification on health status and school performance of rural primary school children.

Single interventions for helminthic infections and micronutrient deficiencies are effective, but it is not clear whether combined interventions will provide equal, additive or synergistic effects to improve children's health. The study objective was to determine the impact of single and combined interventions on nutritional status and scholastic and cognitive performance of school children. A double-blind, randomized, placebo-controlled trial in 11 rural South African primary school randomly allocated 579 children aged between 8 and 10 years into six study groups, half of whom received antihelminthic treatment at baseline. The de-wormed and non-de-wormed arms were further divided into three groups and given biscuits, either unfortified or fortified with vitamin A and iron or with vitamin A only, given daily for 16 weeks. The outcome measures were anthropometric, micronutrient and parasite status, and scholastic and cognitive test scores. There was a significant treatment effect of vitamin A on serum retinol (p < 0.01), and the suggestion of an additive effect between vitamin A fortification and de-worming. Fortified biscuits improved micronutrient status in rural primary school children; vitamin A with de-worming had a greater impact on micronutrient status than vitamin A fortification alone and antihelminthic treatment significantly reduced the overall prevalence of parasite infection. The burden of micronutrient deficiency (anaemia, iron and vitamin A) and stunting in this study population was low and, coupled with the restricted duration of the intervention (16 weeks), might have limited the impact of the interventions.

Analysis of Variance↗
PubMed2001

Severe, rapidly progressive human immunodeficiency virus type 1 disease in newborns with coinfections.

AIM: To describe a severe form of rapidly progressive HIV-1 infection manifesting in the neonatal period. METHOD: Prospective cohort study, King Edward VIII Hospital, Durban, South Africa. HIV-1-exposed neonates with hepatosplenomegaly, lymphadenopathy or persistent pneumonia within the first 28 days of life were investigated for perinatal infections. Confirmation of neonatal HIV-1 infection, HIV-1 subtype and clinical outcomes were studied. RESULTS: Twenty-three (72%) of 32 symptomatic HIV-1-exposed neonates recruited at a mean of 15.2 days were HIV-1-infected. HIV-1 infection was detected in 5 patients who were tested within 48 h of birth, confirming congenital infection. Congenital infection was not excluded in any case. Median neonatal viral load at recruitment was 471,932 copies/ml and median CD4 was 777 cells/mm3. The predominant clinical presentation was growth retardation and prematurity. Perinatal infections detected included: tuberculosis (8), syphilis (6) and cytomegalovirus (10). All of the neonates with perinatal tuberculosis were HIV-1-coinfected. Maternal and neonatal viral load and CD4 at recruitment were not statistically different between the groups with tuberculosis vs. other coinfections. Gag gene sequence analysis confirmed closely aligned HIV-1 subtype C in mothers and neonates. Nineteen (83%) died by 9 months, with a mean age at death of 3.5 months. CONCLUSIONS: A distinct group of HIV-1-infected babies may clinically manifest in the neonatal period with perinatal coinfections, subsequent rapidly progressive HIV-1 and early death.

AIDS-Related Opportunistic Infections↗
PubMed2001

Rapid definition of five novel HLA-A*3002-restricted human immunodeficiency virus-specific cytotoxic T-lymphocyte epitopes by elispot and intracellular cytokine staining assays.

Human immunodeficiency virus (HIV)-specific cytotoxic T lymphocytes (CTL) play a major role in control of viral replication. To understand the contribution of this antiviral response, an initial step is to fully define the specific epitopes targeted by CTL. These studies focused on CTL responses restricted by HLA-A*3002, one of the HLA-A molecules most prominent in African populations. To avoid the time-consuming effort and expense involved in culturing CTL prior to defining epitopes and restricting alleles, we developed a method combining Elispot assays with intracellular gamma interferon staining of peripheral blood mononuclear cells to first map the optimal epitopes targeted and then define the HLA restriction of novel epitopes. In two A*3002-positive subjects whose CTL responses were characterized in detail, the strongest response in both cases was to an epitope in p17 Gag, RSLYNTVATLY (residues 76 to 86). Using this method, CTL epitopes for which there were no motif predictions were optimized and the HLA restriction was established within 48 to 72 h of receipt of blood. This simple and convenient approach should prove useful especially in the characterization of CTL responses specific to HIV and other viruses, particularly in localities where performing cytotoxicity assays would be problematic.

Amino Acid Sequence↗
PubMed2001

Impact of HIV-1 infection in South Africa.

In a prospective study, 60% of admissions to an academic hospital were infected with HIV. HIV infected children were younger, less likely to have been referred, more likely to have pneumonia and candidiasis, and had more health service attendances. This impact may be alleviated by appropriate primary and secondary level health care.

AIDS-Related Opportunistic Infections↗
PubMed2001

Interferon-gamma and interleukin-10 production among HIV-1-infected and uninfected infants of HIV-1-infected mothers.

Immunologic consequences of exposure to HIV-1 in utero are still poorly understood. This study investigates relationships between type-1 [interferon-gamma (IFN-gamma)] and type-2 (IL-10) cytokine production and maternal-infant HIV-1 transmission. Cord blood leukocytes from deliveries of 71 HIV-1-infected and 11 uninfected mothers were tested for in vitro IFN-gamma and IL-10 production after phytohemagglutinin (PHA) stimulation. The infants of these HIV-1-infected mothers were followed prospectively after birth to determine HIV vertical transmission, and IFN-gamma and IL-10 production was measured again at 6 mo. Median PHA-stimulated IFN-gamma production was 210 pg/mL in cord blood cells from infected and 73 pg/mL from uninfected mothers (p = 0.12), and median PHA-stimulated IL-10 production was 491 pg/mL in cord blood cells from infected and 161 pg/mL from uninfected mothers (p = 0.004). PHA-stimulated IFN-gamma and IL-10 production alone were not significantly associated with transmission, but relationships between the two cytokines differed among infected and uninfected infants of HIV-1-infected mothers. PHA-stimulated IFN-gamma and IL-10 production was positively correlated among infected (r = 0.7, p = 0.12 in cord blood and r = 0.66, p = 0.03 at 6 mo) but not uninfected infants, and stronger relative production of IFN-gamma to IL-10 was observed among exposed uninfected than among infected infants (p = 0.04). Exposure in utero to HIV-1 may augment production of IL-10 detectable in fetal cord blood. Stronger relative production of IFN-gamma to IL-10 in cord blood cells from infants of HIV-1-infected mothers may be associated with protection against perinatal HIV infection.

Female↗
PubMed2001

Focal segmental glomerulosclerosis in children from KwaZulu/Natal, South Africa.

AIM: The aim of this paper was to describe the clinical course, histological grading, response to therapies and complications of nephrotic children with focal segmental glomerulosclerosis (FSGS) in Durban, South Africa. METHODS: The demographic data, response to drug therapy, complications, renal function and disease status at the last hospital visit were recorded in children diagnosed as FSGS on histology. Biopsies were graded according to the degree of glomerulosclerosis and interstitial involvement. RESULTS: Seventy-five children, 32 Indian and 43 Black were studied. FSGS as a proportion of all children seen with nephrotic syndrome, has risen between 1970 to 1995 from 1.8% to 20% in Indian children and 5% to 28% in Black children. Of those children followed for two years or more, the two racial groups were similar with respect to age at presentation, gender, histological grading, hypertension, renal outcome and response to therapies except for cushingoid features (p < 0.7), alopecia (p < 0.003) and respiratory tract infections (p < 0.001) which occurred more frequently in Indian children. Forty-three children were followed for between 2-16 years: 14 (10 Indian and 4 Black (p < 0.5)) (29%) had grade 1 changes, 24(13 Indian, 11 Black (p < 0.98)) (56%) had grade 2 changes, 3 (Indian (p < 0.26)) (7%) had grade 3 changes and 2 (Black (p < 0.17)) grade 4 changes. Over this period 27 (63%) had normal renal function, 6 (14%) died, 4 (9%) developed impaired renal function, 6 (14%) chronic renal insufficiency and 6 (14%) end-stage renal disease. Three of the latter were transplanted. At the last hospital visit, Indian children had remitted more often (p < 0.6) and Black children suffered relapse more frequently (p < 0.03). Two children had spontaneous disease remission, and 5 had sustained remission following a course of prednisolone and/or cyclophosphamide. CONCLUSION: This, one of the largest studies of FSGS in children, shows a marked rise in this condition and some differences between Indian and Black children. The outcome in Black children was not as poor as anticipated.

Biopsy↗
PubMed2001

Re-evaluating criteria for peritoneal dialysis in "classical" (D+) hemolytic uremic syndrome.

BACKGROUND: Indications for peritoneal dialysis in children with post-dysenteric hemolytic uremic syndrome (D+ HUS) have not been thoroughly evaluated. Although early institution of dialysis may reduce mortality, the procedure has attendant complications. AIM: To determine whether the use of more stringent criteria for instituting dialysis had a better outcome to that of using conventional criteria. METHOD: Following an outbreak of Shigella dysenteriae type 1 D+ HUS in KwaZulu/Natal during June 1994 to October 1995, we compared the renal outcome and mortality between two periods: before May 1995 (69 children) when conventional criteria for dialysis were employed and after May 1995 (70 children) when more stringent criteria for dialysis were applied. RESULTS: The mean age of presentation was 35 months, 79 (56.8%) were males. Both groups were comparable except for gut perforation, which was more frequent before May 1995, and hypertension and severe disease, which were more frequent after May 1995. Seventy patients underwent dialysis, 36 (52.2%) before May 1995. There were no significant differences in renal outcome or death following discharge from hospital in both groups. Overall mortality was 20.1%, 15 (53.6%) of the 28 children that demised presented before May 1995. OUTCOME: Accordingly, although children with more severe disease and a higher frequency of hypertension presented after May 1995, there were no significant differences in morbidity or mortality in those using stringent criteria for dialysis, compared to those in whom conventional criteria were used. CONCLUSION: We showed that several children, who would previously have been dialyzed, may be managed conservatively, without an increase in mortality or morbidity.

Analysis of Variance↗
PubMed2001

A health and nutritional profile of rural school children in KwaZulu-Natal, South Africa.

A community-based cross-sectional study was undertaken to measure anthropometric indices, micronutrient status and prevalence of parasite infections in 579 rural South African primary school children. Eleven schools were selected randomly from a Magisterial District in southern KwaZulu-Natal (KZN). In each school, all pupils aged between 8 and 10 years were selected. The following outcome measures were obtained: anthropometric--height for age, weight for age and body mass index; micronutrient status--anaemia, serum ferritin and vitamin A; and prevalence of parasite infections--Ascaris lumbricoides, Trichuris trichiura and Schistosoma haematobium. The observed prevalences were: stunting 7.3%, underweight for age 0.7%, and obesity 3.1%; anaemia 16.5% (Hb < 12 g/dl), vitamin A deficiency 34.7% (serum retinol < 20 micrograms/dl) and 28.1% with reduced serum ferritin (< 12 ng/ml); Trichuris trichiura 53.9%, Ascaris lumbricoides 27.3% and Schistosoma haematobium 24.5%. We conclude that micronutrient deficiency, parasitic infestations and stunting remain significant problems among school-aged children in South Africa. Micronutrient supplementation and de-worming provide opportunities for school-based health promotion and primary health care interventions, and might produce significant health and educational benefits.

Anemia↗
PubMed2001

A new combined DTP-HBV-Hib vaccine--strategy for incorporation of Hib vaccination into childhood immunisation programmes.

OBJECTIVES: To evaluate the immunogenicity and reactogenicity of a pentavalent vaccine prepared by extemporaneously mixing diphtheria-tetanus pertussis-hepatitis B vaccine (DTP-HBV) and lyophilised Haemophilus influenzae type B (Hib)-tetanus conjugate vaccines in the same syringe, compared with the same vaccines given as separate, concomitant administrations. DESIGN: Open, randomised comparative study. SETTING: Durban, South Africa. SUBJECTS: A total of 120 healthy male and female infants were enrolled in the trial and randomised into two groups; group 1 received the combined administration (DTP-HBV-Hib), and group 2 received separate administrations of DTP-HBV and Hib vaccines. Vaccines were given as a three-dose primary vaccination course at 2, 4 and 6 months [corrected] of age. OUTCOME MEASURES: Antibody levels were measured using standard techniques and local and general solicited symptoms were recorded using diary cards. RESULTS: All subjects had seroprotective titres against diphtheria and tetanus; and antipolyribose-ribitol phosphate (PRP) titres > or = 0.15 microgram/ml 1 month after the final dose. A vaccine response (defined as post-vaccination titres > or = 15 ELISA (EL).U/ml in initially seronegative subjects; and as post-vaccination titres > or = pre-vaccination titres in initially seropositive subjects) against the pertussis component was seen in 83% and 85% of subjects in the groups receiving combined and separate administration. No differences were seen in any of the geometric mean titres (GMTs) between the two administrations either 2 months after the second dose or 1 month after the final dose. There was no observed increase in reactogenicity in the group receiving the mixed administration. CONCLUSIONS: The results demonstrate that combined DTP-HBV-Hib vaccine is well tolerated and immunogenic.

Antibodies, Bacterial↗
PubMed2001

The increasing burden of tuberculosis in pregnant women, newborns and infants under 6 months of age in Durban, KwaZulu-Natal.

OBJECTIVES: In spite of the global epidemic of tuberculosis (TB) which has been exacerbated by HIV, the impact of these co-infections on maternal and perinatal health has been limited. We document new evidence from Durban, KwaZulu-Natal, on the increasing effects of TB in pregnant women, neonates and infants. METHOD: Women with TB were prospectively studied at the antenatal clinics and obstetric and labour wards at King Edward VIII Hospital, Durban, between 1996 and 1998. The incidence of TB was calculated, and the population-attributable fraction of TB due to HIV infection in pregnancy was estimated. Concurrently, culture-confirmed cases of Mycobacterium tuberculosis in neonates and infants under 6 months of age at the hospital were documented. RESULTS: One hundred and forty-six cases of maternal TB were detected. TB occurred in 0.1% and 0.6% of maternities in 1996 and 1998 respectively. Overall, TB rates for HIV non-infected maternities was 72.9/10(5), and for HIV-infected maternities, 774.5/10(5). The attributable fraction of TB related to HIV in pregnancy was 71.7%; 10.3% of these mothers died. There was a 2.2-fold increase in the caseload of culture-confirmed TB in neonates and young infants at the hospital. CONCLUSION: In regions where TB and HIV prevalence is high, efforts to improve maternal and perinatal health must include the detection of TB in pregnancy.

Age Factors↗
PubMed2000

Cell-free virus in breast milk of HIV-1-seropositive women.

To examine the prevalence, quantification, and factors that influence HIV in the cell-free compartment of breast milk, we performed reverse transcription polymerase chain reaction (RT-PCR) on samples obtained from HIV-1-infected study subjects. Virus was detected in 86 of 136 samples (63.2%) from 79 study subjects. HIV RNA quantity ranged from undetectable to 227,586 copies/ml. Prevalence and mean viral load were not affected by postnatal ages or maternal vitamin A supplementation. Among study subjects with multiple samples, breast milk viral load did not change at different postnatal ages. Breast milk viral load correlated positively with plasma viral load (r = 0.47; p =.005) and negatively with maternal CD4 count at entry to the study (r = -0.26; p =.02). Mothers of HIV-infected children had a higher proportion of detectable HIV RNA in their breast milk than mothers of uninfected children (p =.03) and higher mean log10 HIV RNA quantities (p =.04). In a multivariate logistic regression model, log10 HIV RNA quantity in breast milk was significantly associated with the risk of mother-child transmission (odds ratio [OR], 2.82; 95% confidence interval [CI], 1.22-6.51). Thus, prevention and treatment of opportunistic infections and of mastitis and early weaning may be important elements of a public health policy that is relevant to women in developing countries with HIV infection. Where available, antiretrovirals may also have an impact on opportunistic infections and mastitis.

Adult↗