Biomedical subjects
H M Coovadia
Publications and source records attributed to H M Coovadia.
Comparison of noninvasive methods for distinguishing steroid-sensitive nephrotic syndrome from focal glomerulosclerosis.
Although renal biopsy is the definitive investigation in kidney disorders and is particularly helpful in distinguishing steroid-responsive nephrotic syndrome (SRNS) from focal glomerulosclerosis (FGS), it is attended by a small risk to the patient. Accordingly, noninvasive tests have been used to predict the response to steroids and the underlying renal histologic diagnosis in nephrotic syndrome. The performance of these tests has, however, not been encouraging. We have therefore compared the reliability of the conventional selectivity index (SI) of serum and urinary transferrin and immunoglobulin G (IgG) against other tests of urinary proteins, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS PAGE), and isoelectric focusing (IEF). SI, SDS PAGE, and IEF were carried out in children with nephrotic syndrome within 2 months of clinical presentation. Thirty-one children who had SRNS were compared with 26 who had biopsy-proved FGS and who were steroid resistant. SDS PAGE and IEF revealed excretion of albumin and transferrin only, with homogeneous anionic charge, respectively, in SRNS but unrestricted excretion of additional proteins IgG, beta2-microglobulin, and lysozyme with heterogeneity of electrical charge in FGS. With SDS PAGE and IEF we were able to predict all children who had SRNS and FGS; the SI test predicted all steroid-resistant patients with FGS but was able to predict only 41.7% of the patients with SRNS. Therefore the negative predictive value for steroid response was 58.8% by SI and 100% by SDS PAGE and IEF; the positive predictive value was 100% by SI, SDS PAGE, and IEF. We illustrate the value of SDS PAGE in guiding management in a further seven children with FGS in whom there was either an initial discordance between renal biopsy results and steroid responsiveness or when biopsy was delayed. Accordingly, SDS PAGE and IEF of urinary proteins appear to be useful tests in the diagnosis and management of SRNS and FGS.
Paediatric HIV infection.
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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.
Direct and indirect tests of pore size and charge selectivity in nephrotic syndrome.
We studied direct and indirect methods of measuring membrane charge by detecting fixed anionic sites with polyethylenimine (PEI) on the glomerular basement membrane (GBM) and Alcian blue on red blood cell (RBC) membrane (ABRBC), respectively, in 40 children with nephrotic syndrome (NS). Size selectivity of the GBM was measured indirectly by fine analysis of urinary proteins with sodium dodecyl sulfate-polyacrylamide gel electrophoresis in 22 of these children. Correlation between ABRBC and PEI was strongest (r = 0.79; p = 0.0037) in 11 children with steroid-responsive NS (SRNS), moderate (r = 0.31) in 10 children with focal glomerulosclerosis (FGS), and absent in 14 children with hepatitis B antigen membranous nephropathy (MGN) and 5 with mesangioproliferative glomerulonephritis (MPGN). ABRBC and PEI were reduced in the group as a whole as compared with their controls (ABRBC: 44.53 +/- 9.81 vs 71.54 +/- 12.14, p < 0.05; PEI: 16.31 +/- 4.34 vs 33.3 +/- 1.09, p < 0.005). This reduction was greater in SRNS (26.35 +/- 7.15 p = 0.004) but was also detected in the remainder of the group taken together (52.31 +/- 26.07, p < 0.001). Excretion of glomerular proteins was restricted by size (< or = 80 kd) in SRNS but unrestricted (< or = 80 kd plus > 80 kd) in FGS, MGN, and MPGN. The main cause of proteinuria is likely to be depletion of negative charge on the GBM in SRNS, and distortion of capillary pore size in MGN and MPGN, with probable overlap of these mechanisms in each disease, especially in FGS. Basement membrane injury appears widespread in SRNS but confined to the kidney in MGN and MPGN.
Effects of the human immunodeficiency virus on tuberculosis in children.
SETTING: Human immunodeficiency virus (HIV) infection has altered the epidemiological and clinical profile of tuberculosis (TB) worldwide. In children however, unlike in adults, very little has been documented about the interaction between the two diseases. OBJECTIVE: To examine the clinical features and response to TB treatment in children with TB and HIV, and compare them with those with TB alone. DESIGN: A prospectively enrolled case study with systematically selected controls was conducted between 1992 and 1994 at King George V tuberculosis hospital, in Durban. Forty children with TB and HIV (Group A) were compared with 40 children with TB alone (Group B). The diagnosis of TB was made in accordance with established criteria. Measures of comparison between the groups included: history of contact with a TB case, clinical presentation on admission, presence of bacille Calmette-Guérin (BCG) scar, reaction to tuberculin test, clinical response to anti-tuberculosis treatment (mean weight gain per month, improved appetite, resolution of chest signs, decreasing size of visceromegaly), radiological response to treatment (assessed according to an objective score on admission, at 6 months and on discharge), other associated diseases, nosocomial infections and survival. RESULTS: The mean age of the children in Group A was 25 months and in Group B 31 months. The clearest differences between the groups on admission were clinical features and response to tuberculin testing. Group A were more frequently anergic to tuberculin testing (P < 0.0001) and more often had symptoms and signs suggestive of TB (P = 0.002). Clinical response to treatment on discharge was worse in Group A than in Group B (P = 0.005). Radiological response to treatment at six months and on discharge was poorer in Group A than in Group B (P = 0.46; P = 0.006, respectively). Six children in group A and none in group B died (P = 0.012). The mean duration of treatment (and therefore period until discharge) was 8.9 months in Group B and 8.5 months in Group A for those who survived. History of contact, evidence of BCG inoculation and nosocomial infections were similar in both groups. CONCLUSION: HIV infection adversely affects the outcome of TB in children as assessed by response to treatment and survival.
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%).
Bacteriuria in children attending a primary health care clinic: a prospective study of catheter stream urine samples.
Urinary tract infection (UTI) in infancy and childhood has received scant attention at primary health care (PHC) level, rarely featuring as one of the common diseases. In a prospective study conducted at a PHC clinic, 16 of 94 children (17%) from whom urine was collected by strict aseptic catheterization had bacteriuria (BU). Twelve of these had associated leucocyturia (> 5 WBC/HPF). The median age of those with BU was 9 months (range 1-30 months). BU rarely occurred in isolation (6%), but was most often detected in association with acute respiratory infection (43%) and acute diarrhoea (19%). No association of BU with mild malnutrition was detected in the 50% of children who were underweight for age. Gram-negative pathogens accounted for 14 cases (87.5%). These pathogens were resistant to commonly recommended antibiotics for UTI. Only five cases of BU returned for follow-up at 3 months; no abnormalities were detected on repeat catheter urine samples, urinary tract ultrasonography, voiding cystourethrogram and DMSA studies in them. From these and other findings we conclude that BU is probably often present in young children with common diseases attending PHC centres in developing countries. Further studies are required to establish exactly the role these pathogens play in the pathogenesis of UTI.
Pneumocystis carinii and cytomegalovirus infections in severely ill, HIV-infected African infants.
Unlike in the industrialized world, in which Pneumocystis carinii and cytomegalovirus (CMV) are major respiratory opportunistic organisms, the causes of severe pneumonia, which accounts for much of the mortality in HIV-infected infants in developing countries, are not known, although tuberculosis has been associated with HIV in adults. We report on post-mortem lung and liver biopsies obtained soon after death from 36 HIV-infected infants and 36 HIV-uninfected matched controls who had been admitted with severe pneumonia to an ICU. Nineteen of the HIV-infected infants were classified by WHO criteria as having AIDS and 17 'symptomatic HIV'. P. carinii and CMV were detected significantly more frequently in lung tissue from the AIDS patients (14 of 18 samples tested, p < 0.01; 14 of 18 samples tested, p < 0.01, respectively) as compared with matched controls. P. carinii was detected in two of 13 lung biopsies from symptomatic HIV infants, but in none of the controls. Lung tissue obtained from AIDS patients had P. carinii and CMV more frequently (p < 0.01, p < 0.01, respectively) than that from symptomatic HIV patients. CMV was also detected in excess in liver tissue from AIDS infants (five of 18 samples) as compared with that from symptomatic HIV (0 of 16; p = 0.03) and matched controls (two of 34; p = 0.04). Ante-mortem investigations revealed more CMV infections in AIDS patients (four of 19) than in matched controls (0 of 36; p < 0.01). Tuberculosis was detected in post-mortem lung tissue from only one patient with symptomatic HIV infection. The finding that pathogens (P. carinii, CMV) most frequently detected in seriously ill African infants with HIV/AIDS are similar to those in their counterparts from industrialized countries has implications for improved management in the former.
Probable association between urinary tract infections (UTI) and common diseases of infancy and childhood: a hospital-based study of UTI in Durban, South Africa.
In a retrospective study of UTI among 54 pediatric patients in a tertiary hospital, a striking finding was that UTI seldom existed as a single condition. In 86 per cent of cases, UTI was part of other common diseases: gastroenteritis (in 35 per cent of UTI patients), protein energy malnutrition (in 43 per cent) and acute respiratory infection (24 per cent). Presenting symptoms were similar in children with or without UTI. Other features included infrequency of urinary tract signs (13 per cent), resistance of infecting organisms to first line antibiotics and urinary tract structural abnormalities in only two patients of 36 investigated by ultrasonograms; both the latter patients had easily diagnosable underlying diseases (TB spine, posterior urethral valves). These findings require confirmation by prospective studies as they may have implications for management of UTI in hospitals in developing countries.
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.
Prospective, controlled study of the outcome of human immunodeficiency virus-1 antibody-positive children admitted to an intensive care unit.
OBJECTIVE: Intensive care resources are both scarce and costly in South Africa. We set out to ascertain whether human immunodeficiency virus (HIV) status affects the spectrum of disease and the prognosis in children treated in pediatric intensive care units (ICUs). DESIGN: A prospective, case-controlled study. SETTING: The pediatric ICU at Kind Edward VIII Hospital, Durban, South Africa. PATIENTS: HIV-positive cases were classified as "acquired immunodeficiency syndrome," "symptomatic HIV," and "HIV-unrelated diseases." Controls were matched for age, race, gender, severity of disease, and admitting diagnosis. MEASUREMENTS AND MAIN RESULTS: THe clinician was blinded to the serostatus of patients. Informed consent and Ethics Committee approval were obtained for HIV testing and the study. Outcome measures were the duration of intermittent positive-pressure ventilation and ICU stay, maximum ventilatory requirements, infectious complications, and mortality. There were 11 cases of acquired immune deficiency (AIDS), 24 cases of symptomatic HIV, and 13 cases of HIV-unrelated diseases. Mortality rates for the three groups were as follows: 100% in patients with AIDS compared with 55% in their controls (p<.01); 38% in patients with symptomatic HIV and 46% in controls. Cytomegalovirus and Pneumocystis carinii infections were significantly increased (p<.01, p<.002, respectively) in patients with AIDS as compared with controls. Outcome measures were similar in those patients with symptomatic HIV and those patients with HIV-unrelated diseases, as compared with their respective controls. CONCLUSIONS: Outcome in children with AIDS admitted to the pediatric ICU was significantly worse than the outcome in HIV-uninfected children. However, the number of AIDS patients studied was small. HIV antibody-positive children without AIDS do as well as uninfected controls. Ethics committees in resource-constrained countries may be assisted by such data when making difficult decisions on the admissions of HIV-infected patients to pediatric ICU facilities.
The winter 1996 mass immunisation campaign--is it the best strategy for South Africa at this time?
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A prospective study of bacteriuria and pyuria in catheter specimens from hospitalized children, Durban, South Africa.
In a prospective study of 180 children admitted consecutively to King Edward VIII Hospital, bacteriuria (BU) was detected in 47 (26%), associated with pyuria in 35. BU occurred in association with other common childhood diseases in all but one child: acute lower respiratory tract infection (LRTI) in 43%, gastro-enteritis (GE) in 34% and protein energy malnutrition (PEM) in 26%. Conversely, BU was detected in 24% of children with LRTI, 33% with GE and 38% with PEM. Children with or without BU thus presented with similar symptoms and signs, except for vomiting and dehydration which were more frequent in those with BU. The male:female ratio was higher in BU under 2 years of age. Localizing urinary tract symptoms and signs were infrequent. Only one of the 35 children in whom ultrasonography was performed showed structural defects. The organisms detected (mainly Escherichia coli) were resistant to commonly used antibacterial drugs. There was a high specificity for dipstix testing, but low sensitivity, possibly because of sampling by catheter. There were seven deaths, three with and four without BU. Other illnesses contributed to death in all cases. Our findings have implications for the management of children who are hospitalized for common diseases in developing countries. It is not clear whether pyuria and BU were transient or indicative of serious disease of the kidney and urinary tract.
Serum vitamin A (retinol) concentrations and association with respiratory disease in premature infants.
Vitamin A has been shown to be important in immunity and in differentiation of epithelial tissues. Serum concentrations of vitamin A (retinol) were measured at birth, in 54 preterm and 24 full term infants. Vitamin A concentrations were significantly lower in the preterm compared to the full term infants (9.81 +/- 0.58 micrograms/dl v. 15.58 +/- 1.00 micrograms/dl, P = 0.0001). Serum retinol and birth weight were positively correlated (r = 0.39, P = 0.0004); however, there was no correlation between maternal and infant vitamin A concentrations. The initially reduced vitamin A levels in the preterm infants were not associated with respiratory distress syndrome or pneumonia.
Epidemic Shigella dysenteriae type 1 in Natal.
Since its first isolation in South Africa in 1994, Shigella dysenteriae type 1 has now spread to cause an epidemic outbreak in Natal Kwazulu, resulting in a steep rise in admissions for dysentery and the haemolytic uraemic syndrome in children. We report on the epidemic as it has evolved so far. A large outbreak is to be expected in South Africa in view of large scale poverty, lack of housing, and adequate water and sanitation, unless urgent public health measures are taken.
Predicting perinatal human immunodeficiency virus infection by antibody patterns.
The evolution of human immunodeficiency virus type 1 (HIV-1) antibody titers determined by enzyme-linked immunosorbent assay between birth and 18 months of age was investigated in 118 babies born to HIV-1-seropositive South African mothers. By 18 months 41 (34.7%) children were diagnosed as HIV-1-infected by standard criteria. All 77 uninfected babies cleared maternal antibodies by 15 months; 94.5% of these babies seroreverted by 12 months. By 9 months of age a significant difference (P < 0.05) was noted between antibody decay rates in infected and uninfected children. Of the children subsequently shown to be uninfected, 95.8% demonstrated > or = 50% decay in antibody titers between 6 and 9 months; only 1 in the infected group showed a similar pattern (sensitivity, 97.8%; specificity, 93.8%). The approach of assessing the progression of antibody decay in infected and uninfected babies makes it a feasible and useful tool for estimating vertical transmission rates and diagnosis of perinatal HIV-1 infection earlier than standard practice.
The effects of vitamin A supplementation on the morbidity of children born to HIV-infected women.
OBJECTIVE: The effects of vitamin A supplementation on morbidity of children born to human immunodeficiency virus (HIV)-infected women were evaluated in a population where vitamin A deficiency is not endemic. METHODS: A randomized, placebo-controlled trial of vitamin A supplementation was carried out in 118 offspring of HIV-infected women in Durban, South Africa. Those assigned to receive a supplement were given 50,000 IU of vitamin A at 1 and 3 months of age; 100,000 IU at 6 and 9 months; and 200,000 IU at 12 and 15 months. Morbidity in the past month was then recalled at each follow-up visit. Analysis was based on 806 child-months. RESULTS: Among all children, the supplemented group had lower overall morbidity than the placebo group (OR = 0.69; 95% confidence interval [CI] = 0.48, 0.99). Among the 85 children of known HIV status (28 infected, 57 uninfected), morbidity associated with diarrhea was significantly reduced in the supplemented infected children (OR = 0.51; 95% CI = 0.27, 0.99), whereas no effect of supplementation on diarrheal morbidity was noted among the uninfected children. CONCLUSION: In a population not generally vitamin A deficient, vitamin A supplementation for children of HIV-infected women appeared to be beneficial, reducing morbidity. The benefit was observed particularly for diarrhea among HIV-infected children.