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Biomedical subjects

H M Coovadia

Publications and source records attributed to H M Coovadia.

At least 19 recordsLinked to original sources
PubMed2006

Failure of standard antimicrobial therapy in children aged 3-59 months with mild or asymptomatic HIV infection and severe pneumonia.

OBJECTIVE: To determine whether children aged 3-59 months with mild or non-symptomatic human immunodeficiency virus (HIV) infection and WHO-defined severe pneumonia have a higher failure rate than do HIV-uninfected children when treated with the standard WHO treatment of parenteral penicillin or oral amoxicillin. METHODS: This study was a planned sub-analysis of a randomized trial of 3-59-month-old children presenting with WHO-defined severe pneumonia (the APPIS study). We included two sites with high HIV prevalence in Durban, South Africa and Ndola, Zambia. Primary outcome measures were clinical treatment failure at day 2 and day 14. CLINICALTRIALS.GOV IDENTIFIER: CT00227331http://www.clinicaltrialsgov/show/NCT00227331). FINDINGS: Of the 523 children enrolled, HIV status was known for 464 participants; 106 (23%) of these were infected with HIV. By day 2, 57 (12.3%) children had failed treatment and 110 (23.7%) failed by day 14. Twenty (18.9%) HIV-infected children failed by day 2 compared with 37 (10.3%) uninfected children (adjusted odds ratio (OR) 2.07; 95% confidence interval (CI): 1.07-4.00). Thirty-four (32.1%) HIV-infected children failed treatment by day 14 compared with 76 (21.2%) uninfected children (adjusted OR 1.88; 95% CI: 1.11-3.17). Analysis stratified by age showed that the greatest differential in treatment failure at day 2 and day 14 occurred in the children aged 3-5 months. CONCLUSIONS: HIV-infected children with severe pneumonia fail WHO-standard treatment with parenteral penicillin or amoxicillin at day 2 and day 14 more often than do HIV-uninfected children, especially young infants. Standard case management of acute respiratory infection (ARI) using WHO treatment guidelines is inadequate in areas of high HIV prevalence and reappraisal of empiric antimicrobial therapy is urgently needed for severe pneumonia associated with HIV-1.

Amoxicillin↗
PubMed2005

Challenges in the provision of ICU services to HIV infected children in resource poor settings: a South African case study.

The HIV/AIDS epidemic has placed increasing demands on limited paediatric intensive care services in developing countries. The decision to admit HIV infected children with Pneumocystis carinii pneumonia (PCP) into the paediatric intensive care unit (PICU) has to be made on the best available evidence of outcome and the ethical principles guiding appropriate use of scarce resources. The difficulty in confirming the diagnosis of HIV infection and PCP in infancy, issues around HIV counselling, and the variance in the outcome of HIV infected children with PCP admitted to the PICU in African studies compound this process. Pragmatic decision making will require evaluation of at least three ethical questions: are there clinical and moral reasons for admitting HIV positive children with PCP to the PICU, should more resources be committed to caring for HIV children who require the PICU, and how can we morally choose candidates for the PICU? Those working in the PICU in HIV endemic regions need to make difficult personal decisions on effective triage of admissions of HIV infected children with PCP based on individual case presentation, availability of resources, and applicable ethical principles.

Child↗
PubMed2005

Routinely available cotrimoxazole prophylaxis and occurrence of respiratory and diarrhoeal morbidity in infants born to HIV-infected mothers in South Africa.

OBJECTIVES: To examine the influence of cotrimoxazole (CTM) prophylaxis on incidence of lower respiratory tract infections (LRTIs) and diarrhoea. DESIGN: A prospective observational cohort study. Morbidity and feeding data on infants born to HIV-infected mothers were collected routinely at clinic visits at 1 week, 6 weeks and 3 months, and 3-monthly thereafter, with blood drawn for determining HIV status. SETTING: Two hospitals in Durban, South Africa. In one hospital (King Edward VIII Hospital), infants born to HIV infected mothers received CTM prophylaxis and in the other (McCord Hospital) infants did not receive CTM prophylaxis. SUBJECTS: Infants born to HIV-infected mothers. Outcome measures. Incidence of LRTI and diarrhoea. RESULTS: In multivariate analysis controlling for breast-feeding status, number of clinic visits and HIV infection status, HIV infected infants with access to CTM prophylaxis had a significantly lower incidence of LRTI (82%) than those without access to prophylaxis. However in HIV-uninfected infants, this was not the case. CTM prophylaxis was associated with a non-significant increased risk for diarrhea in both infected (odds ratio (OR) 1.58, p = 0.45) and uninfected infants (OR 1.52, p = 0.10). CONCLUSIONS: This observational study confirms current thinking that CTM prophylaxis is protective against LRTIs in HIV-infected children. However, because of a possible association between CTM prophylaxis and an increased risk of diarrhoea, HIV status of infants should be determined as early as possible in order to prevent unnecessary exposure of uninfected infants to CTM prophylaxis, while further studies to quantify both beneficial and adverse effects of CTM prophylaxis are undertaken.

AIDS-Related Opportunistic Infections↗
PubMed2004

Colloquium report: improving the health of school age children in an era of HIV/AIDS in Durban, South Africa.

Increased morbidity and mortality due to the HIV/AIDS epidemic in South Africa necessitates the examination of policies for the protection and support of school age children. At a colloquium held in Durban participants from government and non-government health and education sectors briefed delegates on key policies and programmes for promoting the health and mental health of school age children. Researchers gave evaluative accounts of the impacts of these measures and presented an overview of South African children's health and mental health needs. In the discussions that followed four critical issues emerged: intersectoral collaboration, accountability, retraining middle management, and a more comprehensive strategy to support pupils and teachers infected and affected by HIV/AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed2004

Vertical transmission of Mycobacterium tuberculosis in KwaZulu Natal: impact of HIV-1 co-infection.

BACKGROUND: Increases in perinatal TB have paralleled the exacerbation of the TB epidemic in KwaZulu Natal. The exact risks for vertical transfer of Mycobacterium tuberculosis (VTRTB) to the baby are unknown, as is the impact of HIV-1 co-infection, which frequently accompanies maternal TB disease in the region. DESIGN: Prospective case series study of 82 HIV-1-infected and 25 non-infected pregnant mothers, King Edward VIII Hospital, KwaZulu Natal, South Africa. RESULTS: Perinatal mortality in HIV-1/TB diseased mothers was 85/1000 and associated with maternal anaemia (P = 0.02); 46% of newborns were premature, 66% low birth weight and 49% intrauterine growth restricted. These were significantly higher than overall hospital rates (P < 0.01, OR 4.8, 95%CI 3.2-7.0). Sites of detection of maternal TB, distribution of bacteriologically-proven TB, obstetric comorbidity and perinatal morbidity were similar in HIV-1-infected and non-infected mothers. VTRTB was detected in 16 newborns (16%), occurring similarly in bacteriologically-proven and suspected maternal TB disease, with no difference between HIV-1-infected and non-infected mothers. Eleven newborns with VTRTB were HIV-1 exposed; 64% acquired HIV-1 and died from rapidly progressive disease by 10 months of age. HIV-1-infected mothers and their exposed newborns had significantly lower CD4 counts. No association between perinatal maternal viral load, CD4 count or VTRTB was detected. CONCLUSION: Mothers with TB disease in pregnancy are at risk for significant perinatal morbidity, mortality and VTRTB.

AIDS-Related Opportunistic Infections↗
PubMed2003

Safety of the intradermal Copenhagen 1331 BCG vaccine in neonates in Durban, South Africa.

OBJECTIVE: To evaluate the safety of the intradermal Copenhagen BCG vaccine in neonates at different levels of delivery and neonatal units of the Durban Functional Region and surrounding regions. METHODS: A prospective study was carried out over a two-year period between July 1997 and June 1999. All neonates who had been vaccinated with the intradermal vaccine were evaluated at immunization clinics six weeks after immunization, or earlier if adverse effects occurred. FINDINGS: In total, 9763 neonates were examined: in 95.4% the vaccination scar had healed and 1.5% had no visible scar. Adverse events occurred in 3.1%. The proportion of neonates with no visible vaccination scars decreased over the study period, as did the number with adverse events. The lowest rate of adverse events and the highest rates of healed vaccination scars were seen in the tertiary hospital and regional and district hospitals that were in close proximity to the academic centre involved in this study. CONCLUSIONS: In the study sites, the transition from the percutaneous to intradermal route of administration of BCG vaccine was successful and took place without incurring unacceptably high rates of adverse events. To minimize adverse events, however, it is essential to continue training health personnel involved in implementing intradermal BCG vaccination programmes.

BCG Vaccine↗
PubMed2003

Molecular characteristics of human immunodeficiency virus type 1 subtype C viruses from KwaZulu-Natal, South Africa: implications for vaccine and antiretroviral control strategies.

The KwaZulu-Natal region of South Africa is experiencing an explosive outbreak of human immunodeficiency virus type 1 (HIV-1) subtype C infections. Understanding the genetic diversity of C viruses and the biological consequences of this diversity is important for the design of effective control strategies. We analyzed the protease gene, the first 935 nucleotides of reverse transcriptase, and the C2V5 envelope region of a representative set of 72 treatment-naïve patients from KwaZulu-Natal and correlated the results with amino acid signature and resistance patterns. Phylogenetic analysis revealed multiple clusters or "lineages" of HIV-1 subtype C that segregated with other C viruses from southern Africa. The same pattern was observed for both black and Indian subgroups and for retrospective specimens collected prior to 1990, indicating that multiple sublineages of HIV-1 C have been present in KwaZulu-Natal since the early stages of the epidemic. With the exception of three nonnucleoside reverse transcriptase inhibitor mutations, no primary resistance mutations were identified. Numerous accessory polymorphisms were present in the protease, but none were located at drug-binding or active sites of the enzyme. One frequent polymorphism, I93L, was located near the protease/reverse transcriptase cleavage site. In the envelope, disruption of the glycosylation motif at the beginning of V3 was associated with the presence of an extra protein kinase C phosphorylation site at codon 11. Many polymorphisms were embedded within cytotoxic T lymphocyte or overlapping cytotoxic T-lymphocyte/T-helper epitopes, as defined for subtype B. This work forms a baseline for future studies aimed at understanding the impact of genetic diversity on vaccine efficacy and on natural susceptibility to antiretroviral drugs.

AIDS Vaccines↗
PubMed2003

Maternal recall of exclusive breast feeding duration.

BACKGROUND: Both the pattern and duration of breast feeding are important determinants of health outcomes. In vertical HIV transmission research, reliable documentation of early breast feeding practices is important in order to correctly attribute postnatal transmission to feeding pattern. AIMS: To validate methods of collecting data on the duration of exclusive breast feeding (EBF) in an area of South Africa with a high HIV prevalence rate. METHODS: A total of 130 mothers were interviewed weekly, postnatally. At every interview a 48 hour and a seven day recall breast feeding history were taken. A subset of 70 mothers also received two intermediate visits per week during which additional 48 hour, non-overlapping, recall interviews were conducted. Ninety three infants were revisited at 6-9 months of age when mothers' recall of EBF duration from birth was documented. The different methods of recalling EBF status were compared against an a priori "best comparison" in each case. RESULTS: Reported breast feeding practices over the previous 48 hours did not reflect EBF practices since birth (specificity 65-89%; positive predictive value 31-48%). Six month EBF duration recall was equally poor (sensitivity at 2 weeks 79%; specificity 40%). Seven day recall accurately reflected EBF practices compared with thrice weekly recall over the same time period (sensitivity 96%, specificity 94%). CONCLUSIONS: 48 hour EBF status does not accurately reflect feeding practices since birth. Long term recall data on EBF are even more inaccurate. We recommend that data on duration of EBF be collected prospectively at intervals of no longer than one week.

Adult↗
PubMed2003

Risk factors for admission and the role of respiratory syncytial virus-specific cytotoxic T-lymphocyte responses in children with acute bronchiolitis.

BACKGROUND: Risk factors for admission of children with acute bronchiolitis have remained controversial. Technological advances in the measurements of cytotoxic T-lymphocyte (CTL) activity, enable respiratory syncytial virus (RSV)-specific CTL activity to be studied in infants with bronchiolitis for the first time. We evaluated risk factors for admission of children with acute bronchiolitis and determined the role of CTL responses in those infected with RSV. METHOD: Children between 3 and 24 months of age presenting with bronchiolitis to the paediatric outpatient department at King Edward VIII Hospital, Durban, over a 1-year period were enrolled. Management included clinical evaluation, nasopharyngeal aspiration, standard treatment and hospitalisation if indicated. Secretions were tested with monoclonal antibodies for RSV and pooled respiratory viruses; shell vial cultures were also established. Permission was requested from parents of RSV-infected subjects for blood draws for specific cytotoxic T-cell assays and CD4/CD8 cells on admission and repeat CTL on day 7. RESULTS: Viruses were identified in 55 of the 114 subjects studied (48.2%). RSV was seen in 41 cases (74.5%). Twenty-three infants (20.2%) required admission. Risk factors associated with inpatient admissions on univariate analysis included younger mean age (7.6 months v. 10.1 months), overcrowding (p < 0.01) and indoor exposure to products of combustion of cooking fuels (p = 0.05). Only the former two were significant on multivariate analysis. RSV-specific CTL responses were obtained in 21 children (51.2%). Responses were either very weak (N = 7) or negative (N = 14) on day 0 and did not alter significantly on day 7. The mean CD4/CD8 ratios in this group were 2.27:1. The highest frequency of CTL was directed against the proteins M4/5/6', with counts ranging from 100 to 400 spot forming cells (sfc)/million. CONCLUSION: Measures to address risk factors identified in this study may decrease the need for hospitalisation from bronchiolitis. The lack of RSV-specific CTL responses in peripheral blood of immunocompetent RSV-infected children suggest an alternative method of induction of immunity or compartmentalisation of immune cells.

Acute Disease↗
PubMed2003

Morbidity in children born to women infected with human immunodeficiency virus in South Africa: does mode of feeding matter?

AIM: To examine infant morbidity risks associated with refraining from breastfeeding where it is used in an attempt to prevent mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV). METHODS: The population consisted of infants born to HIV-infected women in South Africa who were participating in a vitamin A intervention trial to prevent MTCT of HIV. Women chose to breastfeed or formula feed their infants according to UNAIDS guidelines. Actual feeding practices and morbidity were recorded at clinic follow-up visits at I wk, 6 wk, 3 mo and every 3 mo thereafter until 15 mo of age or cessation of breastfeeding. The infant's HIV status was assessed according to a predetermined algorithm. RESULTS: HIV-infected infants who were never breastfed had a poorer outcome than those who were breastfed; 9 (60%) of those who were never breastfed had 3 or more morbidity episodes compared with 15 (32%) of breastfed children [odds ratio (OR) 4.05, 95% confidence interval (95% CI) 0.91-20.63, p = 0.05]. During the first 2 mo of life, never-breastfed infants (regardless of HIV status) were nearly twice as likely to have had an illness episode than breastfed infants (OR 1.91, 95% CI 1. 17-3.13, p = 0.006). CONCLUSION: The significant extra morbidity experienced in the first few months by all never-breastfed infants and at all times by HIV-infected infants who are not breastfed needs to be considered in all decisions by mothers, health workers and policy makers so as not to offset any gains achieved by decreasing HIV transmission through avoiding breastfeeding.

Adult↗
PubMed2003

HIV-exposed infants with acute respiratory failure secondary to acute lower respiratory infections managed with and without mechanical ventilation.

OBJECTIVES: The decision to provide mechanical ventilation (intermittent positive pressure ventilation (IPPV)) to HIV-exposed infants in resource-poor settings has remained difficult owing to problems in confirming HIV infection and the lack of data on outcome. We evaluated the predictive value of the HIV antibody test in confirming infection in infants requiring mechanical ventilation for acute lower respiratory infections (ALRIs), and compared the outcome for children denied access with the outcome for similar subjects who were ventilated. SETTING AND DESIGN: This investigative study was conducted over a 12-month period at the paediatric intensive care unit (PICU) at King Edward VIII Hospital (KEH) in Durban, and at Ngwelezana Hospital in northern KwaZulu-Natal. SUBJECTS: HIV-exposed patients with acute respiratory failure (ARF) secondary to ALRI entering the PICU at KEH were enrolled into the IPPV arm, while similar children who were refused such care at Ngwelezana Hospital were admitted into the non-IPPV arm. Standardised protocols for entry and management of enrolled subjects were utilised. OUTCOME MEASURES: HIV DNA polymerase chain reaction (PCR) testing was performed to establish HIV status. Clinical and laboratory parameters were correlated with HIV status to determine predictors of infection and outcome (survival to discharge). RESULTS: One hundred and sixteen HIV-exposed infants were enrolled, 49 into the IPPV arm and 67 into the non-IPPV arm. The median age of both groups was 3.0 months (0.5-11 months), and the male/female ratio and proportion of infants under 3 months of age were similar in both groups. The predictive values of the HIV antibody test in determining HIV infection in the IPPV and non-IPPV arms were 87.8% and 85.0% respectively. Splenomegaly and a serum globulin of > 35 g/l increased the likelihood of being HIV PCR-positive (p = 0.006 and p = 0.04 respectively). Survival to discharge rates for HIV-infected children in the IPPV and non-IPPV arms were 41.9% and 24.6% respectively (p = 0.08). Age less than 3 months (p = 0.04) and very severe pneumonia (p = 0.007) were the only indicators of poor outcome. CONCLUSION: Mechanical ventilation provided little benefit in HIV-infected children with ARF from ALRI. An HIV antibody test in infants with ALRI and ARF is highly suggestive of HIV infection. Splenomegaly and a serum globulin of greater than 35 g/l were the only useful markers in identifying HIV infection.

Acute Disease↗
PubMed2002

Prevalence, incidence, and mother-to-child transmission of HIV-1 in rural South Africa.

Simple, robust approaches are needed to monitor prevalence, incidence, and mother-to-child transmission of HIV-1 in rural Africa. We have designed a method that uses antibody and viral RNA testing of dried blood spots obtained from mother-infant pairs attending routine immunisation clinics. In our study, prevalence and incidence of HIV-1 was highest in young women in their late teens and early twenties. In children born to infected mothers, prevalence increased from 14% in infants younger than 6 weeks of age to 24% at 3-6 months. The blood-spot approach is an effective method for surveillance of HIV-1 in women and children, and for early identification of incidence of this infection in women of child-bearing age.

Adolescent↗
PubMed2002

Breastfeeding practices in an area of high HIV prevalence in rural South Africa.

UNLABELLED: Exclusive breastfeeding (EBF) from 0 to 6 mo of age is recommended by the World Health Organization as the optimal feeding method for infants, including infants of human immunodeficiency virus (HIV)-infected women from developing countries who choose to breastfeed. EBF may be associated with less risk of postnatal HIV transmission than mixed feeding, but is still uncommonly practised for reasons that are poorly understood. This study aimed to assess EBF rates and the impediments to EBF in a South African rural area of high HIV prevalence where most mothers are unaware of their status. In a longitudinal study, 130 women attending 3 clinics, chosen for their disparate socioeconomic characteristics, were interviewed at weekly postnatal intervals. Follow-up to 16 wk was completed on 119 infants. In an additional cross-sectional survey mothers of 445 infants, aged 0-12 mo, attending immunization clinics were interviewed. In the longitudinal study 46% of infants received non-breast-milk fluids or feeds within 48 h of birth; only 10% were exclusively breastfed for 6 wk and 6% for 16 wk. Supplements, most commonly formula milk, were introduced for perceived milk insufficiency. Feeding choices were mainly self-determined (43% of women), but health staff (22%) and grandmothers (16%) were cited as sources of advice. In the cross-sectional survey caregivers reported that 47% of infants aged 2 wk, 40% aged 6 wk and 33% aged 12 wk had been exclusively breastfed since birth. CONCLUSION: EBF is uncommon in this area in spite of a baby-friendly hospital initiative in the district. Strategies to promote exclusive breastfeeding in developing countries where HIV and infant feeding policies are being formulated must strongly address local perceptions on the need for supplements and sources of feeding advice.

Breast Feeding↗
PubMed2002

Free formula milk for infants of HIV-infected women: blessing or curse?

There is vigorous controversy around whether HIV-infected women in developing countries should choose formula or breastfeeding for their infants. Formula eliminates HIV transmission but incurs risk of increased mortality, whereas breastfeeding has multiple benefits but entails risk of HIV transmission. International guidelines are available but need to be strengthened. This commentary summarizes data on the scale and rate of mother-to-child transmission (MTCT) of HIV through breastfeeding, and the hazards and benefits of breast- and formula-feeding. The case against providing free or subsidized formula to HIV-infected mothers is based on the following: it exacerbates disadvantages of formula feeding; compromises free choice; targets beneficiaries erroneously; creates a false perception of endorsement by health workers; compromises breastfeeding; results in disclosure of HIV status; ignores hidden costs of preparation of formula; increases mixed breastfeeding, which is an unsatisfactory method for all women; requires organization and management of programmes that are complicated and costly; and finally increases the 'spill-over' effect into the normal breastfeeding population. Recommendations to minimize these drawbacks include use of affordable antiretrovirals to reduce MTCT; investments in high-quality, widely available HIV counselling; support for choice of feeding; and exclusive breastfeeding for those who choose to breastfeed.

Acquired Immunodeficiency Syndrome↗
PubMed2002

The impact of human immunodeficency virus 1 on largyngeal airway obstruction in children.

Children with laryngeal airway obstruction (LAO) require admission to the intensive care unit (ICU). The unresolved ethical dilemma of ICU access for HIV infected children in resource poor settings requires further scientific data to help guide triaging. Of 38 children with LAO, 19 had HIV infection. The mortality, need for supportive management, duration of intubation, intermittent positive pressure ventilation, and ICU and hospitalisation stay were similar in the HIV infected group compared to the HIV uninfected group. Episodes of laryngotracheobronchitis were equally distributed between both groups (31.6% v 31.3%), while oropharyngeal/laryngeal candidiasis (26.3%), tuberculosis (15.8%), and benign lymphoid hyperplasia (15.8%) were commonly seen in the HIV infected group.

AIDS-Related Opportunistic Infections↗
PubMed2002

Impact of HIV-1 co-infection on presentation and hospital-related mortality in children with culture proven pulmonary tuberculosis in Durban, South Africa.

BACKGROUND: Diagnosis of tuberculosis (TB) in childhood is difficult and is compounded by HIV-1, as both diseases often co-exist and have many similar features. Most studies from developing countries have included subjects in whom the diagnosis of TB is suspected but not proven. We therefore compare the findings in HIV-infected and non-HIV-infected children with culture-proven TB. METHODS: Records were obtained from the laboratory at King Edward VIII Hospital, Durban, South Africa, between January 1998 and December 1999. Children aged 0-12 years with proven pulmonary tuberculosis (sputum, gastric washing or endotracheal aspirate culture for Mycobacterium tuberculosis) from the paediatric medical wards and intensive care unit were included in the study. A retrospective chart review of demographic data, clinical presentation, diagnostic modalities for TB, HIV-1 result, management and outcome were evaluated. RESULTS: Of 138 culture-proven cases of TB identified during the study period, the medical records of 118 (86%) could be traced. Of these, 57 (48%) were HIV-1 infected, 44 (37%) non-HIV-1-infected, and in 17 (14%) HIV-1 status was not determined. In contrast to previous studies, this study has shown that TB-HIV co-infection in children is common (48% of all culture-proven cases), the presentation of tuberculosis may be acute (43%), and supportive tests are individually only reliable in confirming a diagnosis in a third of cases. All culture evaluations for M. tuberculosis were positive by 8 weeks. Where other diseases often co-exist with TB and HIV infection and the pressure for hospital in-patient admissions are excessive, the diagnosis of tuberculosis could easily be missed (21.2%). Clubbing and age over 2 years were the most reliable indicators of underlying HIV-1 disease in a child with tuberculosis, while clinical features, radiology and supportive tests were found to be similar between HIV-infected and non-HIV-infected TB cases. Hospital-related mortality, all causes, was higher (17.5%) in the HIV-1-infected than the non-infected group (11.4%). CONCLUSION: The changing pattern of presentation of childhood tuberculosis and the high prevalence of TB in HIV endemic areas has made it imperative to maintain a high index of suspicion, with culture evaluation being an important part of clinical practice.

AIDS-Related Opportunistic Infections↗