Research

Researcher: Prof Refiloe Masekela

Designation: HOD: Department of Paediatrics and Child Health

Study: Severe pneumonia in HIV-infected and exposed infants in a paediatric ICU

Summary: Background. Pneumocystis jiroveci pneumonia is still a common cause of severe disease in HIV-infected infants <5 months of age. Despite attention to the prevention of mother-to-child transmission programme in South Africa (SA), HIV testing remains incomplete and infants are still at risk. The management of Pneumocystis pneumonia requires ventilation strategies and combination antibiotics. Methods. A prospective but open intervention was performed on all HIV-exposed patients admitted with severe pneumonia to the paediatric intensive care unit (PICU) at Steve Biko Academic Hospital, SA, during a 3-year period from January 2009 to December 2011. All patients were treated with ampicillin, amikacin, co-trimoxazole, prednisone and intravenous gancilovir. Highly active antiretroviral therapy (HAART) was initiated in the PICU as soon as tuberculosis was excluded and HIV status confirmed with an HIV viral load (VL). Routine blood and tracheal specimens were cultured for bacteria and tested by direct fluorescent antigen testing for P. jiroveci. Cytomegalovirus (CMV) VL was tested. All infants were ventilated in a standard fashion and none were oscillated. Results. A total of 87 patients were admitted during the 3-year period. Of these, 29 patients were excluded from the study because they were HIV-unexposed. Ten patients died during the 3-year period. In a multivariate analysis of the presence or absence of P. jiroveci, HIV VL, CD4 count, timing of HAART initiation and CMV VL, no single factor was documented to influence mortality. Conclusion. Mortality from Pneumocystis pneumonia continues to decrease in this PICU. No single factor is responsible and yet all therapeutic strategies contribute to survival. A national policy and guideline is urgently required. © 2015, Health and Medical Publishing Group. All rights Reserved.

 

Researcher: Prof Refiloe Masekela

Designation: HOD: Department of Paediatrics and Child Health

Study: Lung function decline is accelerated in South Africans with cystic fibrosis

Summary: Background: Poor nutritional status has been shown to be associated with a significant decline in lung function in patients with cystic fibrosis. There are few data published on the lung function decline and the effects of nutritional status in cystic fibrosis (CF) in South Africa.

Aim: To assess anthropometric parameters (weight, height, body mass index Z-score) in relation to lung function parameters in CF patients.

Methodology: A retrospective chart review of clinical records of participants over the age of five years attending the CF clinic at Steve Biko Academic Hospital from 2005 to 2010.

Results:  Twenty  files  were  reviewed  for  lung  function,  anthropometric  measurements,  gender  and  CF-causing  mutations.  For  anthropometric measurements the average changes were –0.8, –0.5 and 2.0 for weight, BMI and height Z-scores, respectively. A decline in FEV1 of –25.3 (95% CI 39.4; –13.3) over the five-year period was noted, with an average decline of 5.3% per year. For FEF25-75, the average change was –22.4 (95% CI-34.6; –10.2) with a decline of 4.5% per year. Using multivariate analysis, the FEV1was found to be significantly influenced by: age –3.96 (95% CI –7.4; –0.5); p = 0.03, weight 1.8 (95% CI –3.4; –0.9); p = 0.04, BMI Z-score 4.3 (95% CI 5.3; 23.3); p = 0.02 and gender (p = 0.02). The FEF25-75 was significantly influenced by BMI Z-score and gender.

Conclusion: The average lung function decline per year for FEV1 was higher than that seen in developed countries. The decline in FEV1 was related to gender, age, weight and BMI. The decline in FEF25-75 was affected only by BMI Z-score and gender.

 

Lung function decline is accelerated in South Africans with cystic fibrosis. Available from: https://www.researchgate.net/publication/281332821_Lung_function_decline_is_accelerated_in_South_Africans_with_cystic_fibrosis [accessed Nov 6, 2015].

 

Researcher: Ms Yolandie Kriel

Designation: Public Health PhD Student

Study: Continuous Access to the Antiretroviral Treatment (ART) Programme: Understanding Barriers to Retention in Care from the Patients’ Perspectives

Summary: The study examined access to the ART programme in the public health care system and what barriers could result when people left the programme. Theb study  highlighted that factors such as poor administration, loss of files, monthly visits, long waiting times, and poor quality of service from staff in the health care setting could lead to patients leaving the ART programme.

All of these factors result in an increase in the amount of people in facilities which further compounds bottlenecks in the system, compromising patients’ satisfaction.  The perspective of the patients provided unique insight into the everyday lived experiences within the public ART programme.

Numerous factors were highlighted in the study that could result in people disengaging form the programme. She explored four major barriers: physical, organisational, socio-cultural, and economic barriers.

Researcher: Professor Rajendra Bhimma

Designation: Paediatric Nephrologist

Study: Steroid Sensitive Nephrotic Syndrome in Children

Summary: Nephrotic Syndrome (NS) is one of the most frequent glomerular diseases seen in children. Children who go into complete remissin following treatment with corticosteroids are classified as having “steroid sensitive” NS.

In developed countries over 80% of children with idiopathic NS have steroid sensitive disease although response to steroids is somewhat tempered in developing countries, especially in black children, the majority of whom have steroid resistant disease.

The exact pathogenesis of this condition remains elusive. Podocyte injury and proteinuria are the two main issues in the pathogenesis. Recent studies suggest alterations in both innate and adaptive immune responses. There is release of cytokines by T-cells as well as a strong contribution of B-cell immunity. Genetic studies have reported human leucocyte antigen (HLA) class II antigens DR and DQ associations linked to steroid sensitive NS and in small case studies, single gene mutations e.g. PLCE1 although to date no homozygous mutations in NPHS1 or NPHS2 and WT-1 genes have been reported.

Most children with steroid sensitive NS have multiple relapses and a significant percentage also develop steroid dependent NS. These children receive multiples courses of steroids and are at high risk of developing steroid toxicity.

Patient with frequent relapses who develop steroid dependency thus require alternative treatment. Steroids sparing agents used include levamisole, cyclophosphamide, mycophenolate mofetil (MMF), calcineurin inhibitors (cyclosporine and tacrolimus), rituximab and vincristine. The steroid-sparing effects of these agents have greatly reduced the adverse effects seen with long-term use of steroids.

Despite the wide arsenal of agents available, therapy needs to be individualised to achieve optimal care of each child. More randomised controlled trials are required to evaluate the therapeutic and economic efficacy of this agent, define criteria for selection of patients for use of particular agents and to determine the safety profile of these drugs in children.

This article reviews the epidemiology, pathogenesis, clinical presentation, diagnosis, complications, management and long term outcome of children with steroid sensitive NS.

 

Researcher: Professor Rajendra Bhimma

Designation: Paediatric Nephrologist

Study: Mycophenolate mofetil therapy in children with idiopathic membranous nephropathy

Summary: Background: Idiopathic membranous nephropathy (IMN) is a rare form of childhood nephropathy. To date there are no standardized protocols of management for this condition in children. The aim of this study is to report on 4 children with IMN who were treated with mycophenolate mofetil (MMF).

Methods: MMF was given in combination with low dose steroids and angiotensin converting enzyme antagonists in a dose of 1,200 mg/m2 body surface area in two divided doses for a minimum of 6 months.

Results: All children had histopathological findings in keeping with Stage III membranous nephropathy. At the last hospital visit, 3 children had achieved a > 50% reduction of proteinuria with preservation of renal function. One patient who failed to respond progressed to Stage III chronic kidney disease. None of the children who were treated with MMF experienced any major side effects of the drug.

Conclusions: MMF, administered over a limited period, served as a safe and effective immunosuppressive agent in the treatment of this condition, in conjunction with low dose steroids and angiotensin converting enzyme inhibitors. Large multicenter randomized studies of children with IMN are necessary to assess the efficacy and long term safety of MMF.


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