School of Clinical Medicine

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Is IMCI an effective mechanism for delivery of child survival interventions in a high HIV prevalence setting? : a study to determine the effectiveness of the Intergrated Management of Childhood Illness (IMCI) strategy in management of sick children in routine practise in primary health care clinics in South Africa
(2012) Horwood, Christiane.; Rollins, Nigel C.; Adhikari, Miriam.
Introduction: Integrated management of childhood illness (IMCI) is a child survival strategy that has been adopted in South Africa (SA) as the standard of care for managing sick children in the primary health care setting. IMCI includes guidelines for management of paediatric HIV. This study aimed to investigate effectiveness of IMCI as a vehicle to deliver essential child survival interventions, particularly HIV interventions, in routine practise in a high HIV prevalence setting, and to investigate barriers and enabling factors for IMCI implementation. Methods: The study was conducted in Limpopo and KwaZulu-Natal provinces, SA. In the qualitative component, focus group discussions were conducted with IMCI trained health workers and carers of children under 5 years, to explore experiences of IMCI implementation, particularly the HIV component, from the perspective of both target groups. A comparative survey was then conducted. Randomly selected IMCI trained nurses were observed for up to 20 consultations with sick children presenting consecutively to the facility, and their findings compared to those of an IMCI expert who subsequently assessed the child. Observed children were tested for HIV. Results: IMCI trained nurses found IMCI training informative and empowering, and there was agreement among nurses that their skills in managing sick children improved after training. Barriers to IMCI implementation included increased time required for IMCI consultations and lack of support from colleagues. IMCI trained nurses expressed reluctance to implement the HIV component of IMCI, believing it to be unnecessary, unacceptable to mothers and that they lacked the skills to implement HIV care. In total, 77 IMCI trained nurses were observed for a total of 1357 consultations between May 2006 and January 2007; nurses were observed for a mean of 17.7 consultations. Components of the IMCI assessment were frequently omitted; 14/77(18%) nurses asked about all main symptoms in every child. IMCI classifications were often incorrect; 52/112 (46.4%) children with a general danger sign were correctly classified. The HIV component was poorly implemented, 342/1357 (25.2%) children were correctly classified for HIV, although the HIV algorithm performed well when implemented by IMCI experts. Conclusion: IMCI implementation is fragmented and incomplete. Interventions are urgently needed to achieve and maintain high quality health worker performance in implementing IMCI.
Nephrotic syndrome in African and Indian children in South Africa.
(1981) Adhikari, Miriam.
There are comprehensive accounts of the nephrotic syndrome in childhood in temperate countries. Many of the important features of this disease have been known for close on to two decades. The causal link between malaria and nephrosis in tropical Africa has also been recognised and documented for a similar length of time. Very little was known of the nephrotic syndrome in the sub-tropical zones of Africa where malaria is not endemic. Anecdotal evidence in South Africa suggested that African children with this disease appeared to have steroid resistant nephrosis and a more protracted clinical course than expected from prevailing accounts in the literature and that Indian South African children generally responded to steroids. This thesis is the result of detailed investigations in to this disease in African and Indian children in Durban, South Africa. 2. Preliminary Study A preliminary study was undertaken in which 53 (12 African and 41 Indian) children with the nephrotic syndrome defined by clinical and biochemical criteria 1 ii were studied. Renal biopsies were not available on these patients. The results revealed that two thirds of the African children were over 5 years of age and 50% were males. Of the Indian children 50% were under 5 years of age and 50% were males. Nine African children were treated with steroids and 8 did not respond whereas 31 of the 39 Indian children treated clearly responded to steroid therapy. In addition 5 Indian patients were treated with cyclophosphamide and 3 responded. On follow-up 7 of the African children had persistent proteinuria, 2 experienced remissions and 3 were lost to follow-up. All the Indian patients experienced remissions. The differences between the 2 groups of nephrotic patients were quite striking and therefore a more detailed prospective study of this problem was undertaken. 3. Prospective Study of Primary Nephrotic Syndrome One hundred and seventy children of whom 104 were African and 66 Indian with primary nephrotic syndrome were studied. In both racial groups the male sex dominated, Indian children tended to present iii at a younger age group whereas African children presented at two peak ages, 5 years and between 5 - 10 years. 3.1 Histological Differences The histological types found on light microscopic examination of renal tissue were distinctly different between the African and the Indian children. The majority (85.6%) of the African children had 'obvious' glomerular lesions, the commonest being extramembranous nephropathy (29.8%). Although the proliferative group was the single largest group (40%) none of the subgroups exceeded the extramembranous type in their number. Minimal change accounted for only 14.4% of the African children with nephrotic syndrome. The majority of Indian children (72.7%) had minimal change on light microscopy, 9.1% focal glomerulosclerosis and 12.1% had proliferative changes. 3.2 Immunofluorescence Immunofluorescent studies also indicated differences between the two groups of patients. Generally, heavier deposits of immunoglobulins iv and complement components were identified on renal biopsy specimens of African children. This occurred even in MCNS where most African children had heavy IgG, light IgM, IgA and complement components whereas only a few of the Indian children had light IgM deposits. Similar differences were observed in diffuse mesangial proliferative glomerulonephritis and focal glomerulosclerosis where the numbers of patients were comparable. 3.3 Presenting Features Clinical features at presentation in the two groups were different, as expected from the nature of the histological findings in each group. In the African children (all histological groups) haematuria occurred in 35.5%, hypertension 16.3% and renal failure in 2.9%. The clinical features in the Indian children were not too different from MCNS elsewhere. Haematuria occurred in a small percentage (3%) of MCNS but was more frequent (10.7%) in other groups. Hypertension and renal failure occurred infrequently in histological categories other than MCNS where they did not occur at all. 3.4 Course and Outcome In view of the above it was not unexpected to find that the clinical course and outcome in the two groups were quite dissimilar. African patients in certain of the histological groups fared reasonably well, but none of the groups had the excellent prognosis of Indian MCNS. 3.4.1 Minimal Change One third of the African MCNS patients remitted and this was unrelated to steroids. The remainder who were followed for a reasonable duration of time remained proteinuric. None developed signs of serious renal impairment (azotaemia, hypertension). Indian MCNS experienced an excellent prognosis with 97.8% achieving remission and 81.6% being steroid sensitive. One third of these patients had a single episode of nephrosis while frequent relapses occurred in 28.2%. 3.4.2 Extramembranous Nephropathy Patients with extramembranous nephropathy, the largest group in the African patients, experienced hypertension more often (20%) vi and remission less often (30%) than do children in temperate climates. The clinical presentation, course and outcome in the majority of these patients were similar to adults with extramembranous nephropathy. 3.4.3 Proliferative Glomerulonephritis The patients in the proliferative group had a variable outcome depending on the subgroup to which they belonged. In diffuse mesangial proliferation, African patients had a higher incidence of hypertension and fewer remissions and fared less well than Indian patients. The diffuse endocapillary glomerulonephritis, membranoproliferative and focal proliferative nephritis groups of patients suffered severe disease with a failure to remit and progression to death. In the diffuse exudative group, remissions occurred or proteinuria persisted but severe relapse and death did not occur. The worst prognosis was in the focal proliferative group with the highest incidence of persistent relapse. 3.4.4 Focal Glomerular Sclerosis Focal glomerular sclerosis was an unusual vii histological diagnosis in the African child (3.9%) with a poorer prognosis (persistent proteinuria or death) when compared to Indian children in whom one third remitted and the rest had persistent proteinuria. 3.4.5 Tropical Nephropathies It is difficult to comment on the course of the tropical nephropathy (not related to malaria) and tropical extramembranous groups as the numbers are small. However, in tropical extramembranous, none remitted (all African children) and in tropical nephropathy one Indian child remitted but one of 2 African children died and the other had persistent proteinuria. 3.5 Response to Therapy Perhaps the most important practical aspect of the nephrotic syndrome in the African child was the response to steroid therapy. Thirty two African children were given steroid therapy. Thirty (93.7%) did not respond. Five children deteriorated or died during steroid therapy. Very few patients (4) were given cyclophosphamide and none responded. viii Generally intravenous albumen, diuretics and a high protein diet were not very effective in those patients with severe, clinical disease but were of benefit in milder disease. Indian children taken as a whole, responded well to steroid therapy. Seventy-eight percent of the whole group responded to steroids and 21.4% developed cushingoid features. Of the 19 Indian children (all MCNS) treated with cyclophosphamide 63.2% responded of whom about a quarter got toxic side effects (alopecia, darkened nails and leucopenia). Chlorambucil therapy in 4 children (all MCNS) was successful in all. 3.6 Complications Serious infections (septicaemia, peritonitis, urinary tract infection, meningitis, arthritis, osteitis, measles, chicken pox) occurred in 8.7% of the African patients. Eighteen percent had less severe infections. Just over a quarter of the Indian children suffered severe infections. The majority of these patients were MCNS and about 50% were on steroids or cyclophosphamide at the ix time of their infection. Renal biopsy complications were minor, these being abdominal pain and tenderness or transient haematuria. A few patients developed renal haematomas which were detected or monitored by ultrasonography. The single serious complication was the development of a renal abscess at the biopsy site requiring partial nephrectomy. 3.7 Mortality The overall mortality was 5.8%. Seven of the 10 deaths were African children in the Proliferative Group and 3 of the 10 deaths were Indian children. 4. Secondary Nephrotic Syndrome The secondary nephrotics formed an interesting group of patients. Of the 22 patients classified as secondary nephrotics 11 (50%) were related to streptococcal infection either as rapidly progressive glomerulonephritis or transient NS following APSGN. HBsAg was detected in the blood of 8.6% of the African patients. However the HB sAg carrier rate in this age group is 7.4%.The incidence in these patients probably reflects the high incidence in this population group. Collagen vascular disease occurred in 2 patients, both Indian. 5. Conclusions and Recommendations The results of this study demonstrates the strikingly different incidences of the various histological categories in the two race groups studied with a less favourable prognosis and fewer remission rates being achieved in African children. Indian children had more serious infections more often than African children. Steroid and immunosuppressive agents were of no value and probably hazardous in the African child. Some patients deteriorated on these drugs. Indian children who had an excellent response to these drugs were however at significant risk of developing serious infections. Why African children in Durban develop obvious glomerular lesions has not been established. Known or possible aetiological agents such as malaria, schistosomiasis, streptococcal infections and collagen diseases have been excluded. The answer to the above question may in fact lie in genetic predisposition,host factors and environmental influences, either singly or in combination, predisposing to the development of obvious x i glomerular lesions. These require more intensive investigation and judging from the yield of similar studies in other areas of the world expectations have to be guarded.
The role of parenteral phenobarbitone in the treatment of neonatal hyperbilirubinaemia.
(1993) Adam, Omar Farouk.; Adhikari, Miriam.
Abstract available in PDF.
Studies on the mechanisms of proteinuria in kidney diseases of childhood.
(1994) Ramjee, Gita.; Adhikari, Miriam.; Coovadia, Hoosen Mahomed.
Abstract available in PDF.
Transmission rates of HIV-1 and the mortality rate in high risk infants exposed to HIV, in the PMTCT programme, at the Neonatal Unit, of King Edward VIII Hospital , Durban, South Africa.
(2012) Nair, Nadia.; Adhikari, Miriam.
Introduction. Previous studies have established that infants born to mothers with advanced HIV disease and co-infections are smaller, premature and have rapidly progressive HIV disease and an early death. King Edward VIIIth Hospital, in Durban, admits many sick mothers and manages a large proportion of low birth weight and ill newborns. On discharge and follow-up, the mortality and morbidity of these infants are known to be high and are related to the prematurity. How much is related to being HIV exposed is still uncertain. Aim. To determine the perinatal transmission rate of HIV-1 and mortality at 12 months in HIV exposed infants that were admitted to and discharged from the Neonatal Unit, in Durban, South Africa. Methods. In this observational study, data from the outpatient charts of HIV exposed infants that required specialised neonatal care and subsequent follow up, between the period November 2007 and December 2009, were collected. Perinatal transmission rates and mortality of these infants were compared with maternal and infant risk factors. Results. Data on 463 HIV exposed, predominantly low birth weight infants are presented. The median maternal CD4 count was 309cells/mm3 with 16.8% of mothers commenced on HAART. Maternal co-infection with TB was found in 19.2% of the cohort. Early HIV transmission occurred in 11.5% of infants and was influenced by the type of ARV exposure (None, 20%; single dose NVP, 14.3%; dual therapy, 10.6%; maternal HAART, 8.5%). The dual therapy regimen for 7 days was more protective than that for 28 days (p=0.045). HIV infection was associated with higher risk of neonatal sepsis (RR 1.6; 95% CI, 1.1-2.3; p=0.015). The mortality for the cohort at 12 months was 10%. Maternal HAART was associated with a lower mortality: 2.95% vs.10.2% (RR 3.0; 95% CI, 0.4-20.5). There was a higher mortality rate in those that were low birth weight (RR 4.2; 95% CI, 1.02-18.8; p=0.037); those that were HIV infected (RR 4.8; 95% CI, 1.9-11.6; p=0.002) and those that were breastfeeding compared to formula feeding (RR 2.7; 95% CI, 1.1-6.8; p=0.038). Discussion. Rates of HIV transmission within the PMTCT programme were similar to that reported by the Department of Health. Early maternal ARVs for PMTCT prophylaxis, prevents HIV transmission. The coverage of maternal HAART was sub-optimal. Breastfeeding was associated with a higher HIV transmission rate and was most likely associated with non-exclusive breastfeeding during neonatal admission. Recommendations. Maternal HAART or ARV prophylaxis should be commenced early in the pregnancy for the best benefits. Meticulous attention should be paid to the feeding practices of high risk HIV exposed infants admitted for specialised neonatal care.
Validation of bioimpedance against isotope methods for the determination of body composition in HIV infected South African children.
(2010) Sewnath, Alesha.; Chhagan, Meera Kurson.; Adhikari, Miriam.
Abstract available in PDF.

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