Browsing by Author "Eley, Brian"
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- ItemOpen AccessA retrospective description of primary immunodeficiency diseases at Red Cross War Memorial Children's Hospital, Cape Town, South Africa, 1975 – 2017(2020) Moodley, Sashmi; Eley, BrianBackground. The primary immunodeficiency diseases (PIDs) constitute a diverse and everexpanding group of inborn errors affecting a wide range of immune functions. They are not well documented in Sub-Saharan Africa. An important barrier to care is limited awareness of PIDs and their management among health care professionals. This fascinating spectrum of diseases is rapidly expanding worldwide, and not as rare as we think. Genetic characterization and newborn screening for primary Immunodeficiency diseases (PIDs) may be the gold standard in the first world setting but are neither practical nor feasible for our doctors. Yet, other low and middle income countries in the world have also established reasonable services and created registries for children with PIDs, including other African countries. Objective. To describe the spectrum of PIDs at a tertiary paediatric hospital. Methods. A retrospective descriptive study of PIDs diagnosed at Red Cross War Memorial Children's Hospital, Cape Town, South Africa between 1975 and 2017 was undertaken. Results. 252 children with PIDs were identified, spanning 8 of the 9 categories listed in the 2017 classification of the International Union of Immunological Societies. Predominantly antibody deficiencies, combined immunodeficiencies with associated syndromic features, and immunodeficiencies affecting cellular and humoral immunity accounted for 79% of all PIDs. The mean age (standard deviation) at diagnosis was 46 (50) months and the male to female ratio was 1.5:1. A history of parental consanguinity was present in 3 children (1.2%). Recurrent infection was the most prevalent presenting phenotype, manifesting in 70.2% of the patients. Genetic or chromosomal confirmation was obtained in 42/252 (16.7%) of the children. Common interventions used to prevent infection were antimicrobial prophylaxis and immunoglobulin replacement therapy, administered to 37.7% and 36.9% of the patients respectively. Six of seven children who underwent haematopoietic stem cell transplantation (HSCT) had successful outcomes. The 7th patient died 2 months post-HSCT from overwhelming infection. Although we could not account for the children lost to follow up during the study period, 53 (21.0%) deaths were confirmed. Conclusions. Several challenges exist in the recognition and treatment of children with PIDs in our setting. These include limited access to genetic diagnostics and HSCT. Sub-optimal treatment options contribute to the overall mortality of PIDs in South Africa. Greater awareness among clinicians treating children and more laboratory diagnostic capacity are needed to increase the recognition PIDs among children in South Africa. The treatment options that are available in South Africa are unevenly distributed. Hence, treatment capacity should be expanded throughout the country, especially advanced interventions such as HSCT. Ongoing reporting of registries such as ours and increased community awareness should strengthen the lobby for greater investment in rare diseases such as the PIDs.
- ItemOpen AccessA retrospective description of primary immunodeficiency diseases at Red Cross War Memorial Children's Hospital, Cape Town, South Africa, 1975 – 2017(2020) Moodley, Sashmi; Eley, BrianBackground. The primary immunodeficiency diseases (PIDs) constitute a diverse and everexpanding group of inborn errors affecting a wide range of immune functions. They are not well documented in Sub-Saharan Africa. An important barrier to care is limited awareness of PIDs and their management among health care professionals. This fascinating spectrum of diseases is rapidly expanding worldwide, and not as rare as we think. Genetic characterization and newborn screening for primary Immunodeficiency diseases (PIDs) may be the gold standard in the first world setting but are neither practical nor feasible for our doctors. Yet, other low and middle income countries in the world have also established reasonable services and created registries for children with PIDs, including other African countries. Objective. To describe the spectrum of PIDs at a tertiary paediatric hospital. Methods. A retrospective descriptive study of PIDs diagnosed at Red Cross War Memorial Children's Hospital, Cape Town, South Africa between 1975 and 2017 was undertaken. Results. 252 children with PIDs were identified, spanning 8 of the 9 categories listed in the 2017 classification of the International Union of Immunological Societies. Predominantly antibody deficiencies, combined immunodeficiencies with associated syndromic features, and immunodeficiencies affecting cellular and humoral immunity accounted for 79% of all PIDs. The mean age (standard deviation) at diagnosis was 46 (50) months and the male to female ratio was 1.5:1. A history of parental consanguinity was present in 3 children (1.2%). Recurrent infection was the most prevalent presenting phenotype, manifesting in 70.2% of the patients. Genetic or chromosomal confirmation was obtained in 42/252 (16.7%) of the children. Common interventions used to prevent infection were antimicrobial prophylaxis and immunoglobulin replacement therapy, administered to 37.7% and 36.9% of the patients respectively. Six of seven children who underwent haematopoietic stem cell transplantation (HSCT) had successful outcomes. The 7th patient died 2 months post-HSCT from overwhelming infection. Although we could not account for the children lost to follow up during the study period, 53 (21.0%) deaths were confirmed. Conclusions. Several challenges exist in the recognition and treatment of children with PIDs in our setting. These include limited access to genetic diagnostics and HSCT. Sub-optimal treatment options contribute to the overall mortality of PIDs in South Africa. Greater awareness among clinicians treating children and more laboratory diagnostic capacity are needed to increase the recognition PIDs among children in South Africa. The treatment options that are available in South Africa are unevenly distributed. Hence, treatment capacity should be expanded throughout the country, especially advanced interventions such as HSCT. Ongoing reporting of registries such as ours and increased community awareness should strengthen the lobby for greater investment in rare diseases such as the PIDs.
- ItemOpen AccessA ten-year review of ESBL and non-ESBL Escherichia Coli Bloodstream infections among children at a tertiary referral hospital in South Africa(2019) Malande, Oliver Ombeva; Eley, Brian; Nuttall, JamesIntroduction: Bloodstream infection (BSI) is an important cause of morbidity and mortality in children (1). There are few descriptions of Escherichia coli (E. coli) BSI in children, particularly in Africa, yet E. coli is increasing in importance as a cause of antibiotic-resistant infection in paediatric settings. Methods: In this retrospective, descriptive study aspects of E. coli BSI epidemiology are described over a 10-year period including incidence risk, risk factors for extended spectrum β-lactamase (ESBL)- producing E. coli BSI, antibiotic susceptibility of the bacterial isolates and outcome including risk factors for severe disease. Results: There were 583 new E. coli BSI episodes among 217,483 admissions, an overall incidence risk of 2.7 events/1,000 hospital admissions. Of 455 of these E. coli BSI episodes that were analysed, 136 (29.9%) were caused by ESBL-producing isolates. Risk factors for ESBL-producing E. coli BSI included hospitalization in the 28-day period preceding E. coli BSI episodes and having an underlying chronic illness other than HIV infection at the time of the E. coli BSI. None of the E. coli isolates were resistant to carbapenems or colistin. The mortality rate was 5.9% and admission to the intensive care unit was required in 12.3% of BSI episodes. Predictors of severe disease included age less than 1 month, hospitalization in the 28-day period preceding E. coli BSI and BSI without a definable focus. Conclusions: These findings extend our understanding of E. coli BSI in a sub-Saharan African setting, provide useful information that can guide empiric treatment choices for community- and hospitalacquired BSI and help inform prevention strategies.
- ItemOpen AccessAdherence to antiretroviral therapy in young children in Cape Town, South Africa, measured by medication return and caregiver self-report : a prospective cohort study(2010) Davies, Mary-Ann; Boulle, Andrew; Eley, BrianExcellent adherence to antiretroviral therapy (ART) is necessary if HIV-infected children are to experience the dramatically improved outcomes that this treatment affords. However, there is very limited data on adherence to antiretroviral therapy in Africa, with few studies that examine the predictive value of low technology measures of adherence in terms of viral and immune outcomes. In addition there are no long terms studies of adherence in young children in Africa.
- ItemOpen AccessAdherence to antiretroviral therapy in young children in Cape Town, South Africa, measured by medication return and caregiver self-report: a prospective cohort study(BioMed Central Ltd, 2008) Davies, Mary-Ann; Boulle, Andrew; Fakir, Tanzeem; Nuttall, James; Eley, BrianBACKGROUND:Antiretroviral therapy (ART) dramatically improves outcomes for children in Africa; however excellent adherence is required for treatment success. This study describes the utility of different measures of adherence in detecting lapses in infants and young children in Cape Town, South Africa. METHODS: In a prospective cohort of 122 HIV-infected children commenced on ART, adherence was measured monthly during the first year of treatment by medication return (MR) for both syrups and tablets/capsules. A questionnaire was administered to caregivers after 3 months of treatment to assess experience with giving medication and self-reported adherence. Viral and immune response to treatment were assessed at the end of one year and associations with measured adherence determined. RESULTS: Medication was returned for 115/122 (94%) children with median age (IQR) of 37 (16 - 61) months. Ninety-one (79%) children achieved annual average MR adherence [greater than or equal to] 90%. This was an important covariate associated with viral suppression after adjustment for disease severity (OR = 5.5 [95%CI: 0.8-35.6], p = 0.075), however was not associated with immunological response to ART. By 3 months on ART, 13 (10%) children had deceased and 11 (10%) were lost to follow-up. Questionnaires were completed by 87/98 (90%) of caregivers of those who remained in care. Sensitivity of poor reported adherence (missing [greater than or equal to] 1 dose in the previous 3 days) for MR adherence <90% was only 31.8% (95% CI: 10.7% - 53.0%). Caregivers of 33/87 (38.4%) children reported difficulties with giving medication, most commonly poor palatability (21.8%). Independent socio-demographic predictors of MR adherence [greater than or equal to] 90% were secondary education of caregivers (OR = 4.49; 95%CI: 1.10 - 18.24) and access to water and electricity (OR = 2.65; 95%CI: 0.93 - 7.55). Taking ritonavir was negatively associated with MR adherence [greater than or equal to] 90% (OR = 0.37; 95%CI: 0.13 - 1.02). CONCLUSION: Excellent adherence to ART is possible in African infants and young children and the relatively simple low technology measure of adherence by MR strongly predicts viral response. Better socio-economic status and more palatable regimens are associated with better adherence.
- ItemOpen AccessAntiretroviral treatment for children(Health and Medical Publishing Group, 2006) Eley, Brian; Davies, Mary-Ann; Apolles, Patti; Cowburn, Carol; Buys, Heloise; Zampoli, Marco; Finlayson, Heather; King, Spasina; Nuttall, JamesObjective: To describe the response of children during their first year on highly active antiretroviral therapy (HAART). Design: Retrospective, descriptive. Setting. Tertiary, referral hospital. Subjects: All HIV-infected children commenced on HAART from 1 August 2002 until 31 December 2004. Outcome measures: Children were retrospectively restaged using the WHO 4-stage clinical classification and CDC immunological staging system. After commencing HAART, patients were assessed at monthly intervals for the first 6 months and thereafter mostly 3-monthly. Baseline and 6- monthly CD4 counts and viral loads were performed. Results. Of 409 children commenced on HAART, 50.6% were < 2 years old, 62.7% had severe clinical disease and 76.6% had severe immune suppression. After 1 year, 65.8% were alive and continued HAART at the hospital, 11.2% had been transferred to another antiretroviral site, 15.4% had died, 4.6% were lost to follow-up and treatment had been discontinued in 2.9%. Kaplan-Meier survival estimate for 407 children at 1 year was 84% (95% confidence interval (CI) 80 - 87%). On multivariate analysis, survival was adversely affected in children with WHO stage 4 v. stage 2 and 3 disease (adjusted hazard ratio (HR): 5.26 (95% CI 2.25 - 12.32), p = 0.000), age < 12 months (adjusted HR: 2.46 (95% CI 1.48 - 4.09), p = 0.001) and CD4 absolute count (per 100 cell increase) (adjusted HR: 0.93 (95% CI 0.88 - 0.98), p = 0.013). In a separate multivariate model including only children with an initial viral load (N = 367), viral load r 1 million copies/ml (adjusted HR: 1.84 (95% CI 1.03 - 3.29)) and taking a protease inhibitor (PI)-based regimen (adjusted HR: 2.25 (95% CI 1.10 - 4.61)) were additionally independently associated with poorer survival; however, young age was not a significant predictor of mortality, after adjusting for viral load (p = 0.119). After 1 year of HAART 184/264 (69.7%) of children had a viral load < 400 copies/ml. Comparative analysis showed significant improvements in growth, immunological status and virological control. Conclusion: HAART can improve the health of many HIVinfected children with advanced disease, including those aged less than 2 years in resource-limited settings.
- ItemOpen AccessAspect of tuberculosis case management at Red Cross Children's Hospital(2010) Moore, David Paul; Eley, BrianAim: To describe the spectrum of tuberculosis in children <15 years of age attending Red Cross War Memorial Children's Hospital between January 2006 and December 2008. Methods: A retrospective review of a paper-based Notifications Register and a database of culture-confirmed tuberculosis were undertaken. Laboratory and clinical data were analysed. Results: 1,314 episodes of tuberculosis were identified amongst 1,300 children. 433 (33%) of all cases were culture-confirmed; however, 120 (27.7%) of all culture-confirmed cases were not recorded in the paper-based Notifications Register. Conclusions: To improve the clinical service, detection of HIV co-infection in children undergoing evaluation for tuberculosis should be enhanced and strategies adopted to ensure that all children with culture- confirmed disease are notified and access antituberculosis therapy.
- ItemOpen AccessBlood stream infections in oncology patients at Red Cross War Memorial Children's Hospital, Cape Town(2017) Mvalo, Tisungane Knox Titus; Davidson, Alan; Eley, BrianBackground: Infections cause significant morbidity and mortality in children with cancer, which may be related to the cancer or treatment received. There is paucity of data on the epidemiology of bloodstream infection (BSI) in sub-Saharan Africa. To address this knowledge gap, the present study was conducted at Red Cross War Memorial Children's Hospital (RCWMCH) in Cape Town, South Africa. Methods: Structured literature review: From 1 April 2016 to 31 May 2016 a PubMed search was undertaken on BSI in Paediatric Oncology. The search string used was (bacteraemia OR blood stream infection) AND (paediatric OR pediatric) AND (oncology). Studies that did not describe infection patterns, risk factors for infection, morbidity/mortality, articles not in English and those exclusively describing neonatal or ICU patients were excluded from full review. Retrospective cohort study: A retrospective cohort study was conducted at the haematology-oncology unit of RCWMCH. All positive blood cultures from RCWMCH oncology patients taken between 1 January 2012 and 31 December 2014 were retrieved to identify patients who had BSI. Results: Structured literature review: 508 abstracts / articles were initially retrieved and screened. 478 studies were excluded as per the literature review exclusion criteria. Thus, 30 articles were included in full analysis, 17 retrospective studies, 4 prospective multicentre studies, 6 prospective single centre studies, 2 systematic reviews and 1 case report. All were observational studies. This literature review showed that BSI is a frequent and important cause of morbidity and mortality in paediatric oncology. Gram-positive bacteria was noted to be the leading type of pathogen causing BSI. Increased risk of BSI may be from the cancer itself, chemotherapy, hospitalisation, central venous catheter insertion, and oncology patients were at risk of multi-drug resistant infection. Research gaps noted included paucity of studies from Sub-Saharan Africa, limited analysis of the antimicrobial susceptibility of causative microorganisms and limited description of fungal BSI in oncology patients. Retrospective cohort study: From 436 positive blood culture results, 150 BSI episodes were identified amongst 89 patients; 49.1% of the culture isolates were Gram-positive bacteria, 41.6 were Gram-negative bacteria and 9.3% were fungal. Coagulase Negative Staphylococcus and Viridans Group Streptococcus were the most common Gram-positive isolates, and Escherichia coli and Klebsiella species the commonest Gram-negative isolates. The majority of BSI episodes occurred in patients with haematological malignancies (74%), in the presence of severe neutropaenia (76.4%) and whilst on or following chemotherapy (88%). Complications occurred in 14% of the BSI episodes. Fungal infections had the highest prevalence of complications (21.4%). Three children died during BSI as a result of multidrug resistant isolates, giving a case-fatality rate of 2%. Conclusion: The findings of our cohort study show that BSI are mainly caused by Gram-positive bacteria and associated with a low case-fatality rate. The results of this study are consistent with worldwide experience of BSI in paediatric oncology patients. This study provides an understanding of the spectrum of organisms causing BSI and the outcome of BSI in a sub-Saharan African context.
- ItemOpen AccessBloodstream infections at a tertiary level paediatric hospital in South Africa(BioMed Central, 2017-12-06) Lochan, Harsha; Pillay, Vashini; Bamford, Colleen; Nuttall, James; Eley, BrianBackground: Bloodstream infection (BSI) in children causes significant morbidity and mortality. There are few studies describing the epidemiology of BSI in South African children. Methods: A retrospective descriptive cohort study was conducted at a paediatric referral hospital in Cape Town, South Africa. The National Health Laboratory Service (NHLS) microbiology database was accessed to identify positive blood culture specimens during the period 2011–2012. Demographic and clinical details, antimicrobial management and patient outcome information were extracted from medical and laboratory records. Antibiotic susceptibility results of identified organisms were obtained from the NHLS database. Results: Of the 693 unique bacterial and fungal BSI episodes identified during the study period, 248 (35.8%) were community-acquired (CA), 371 (53.5%) hospital-acquired (HA) and 74 (10.7%) healthcare-associated (HCA). The overall risk was 6.7 BSI episodes per 1000 admissions. Escherichia coli, Staphylococcus aureus and Streptococcus pneumoniae were the most frequent causes of CA-BSI and Klebsiella pneumoniae, Acinetobacter baumanii and S. aureus were most commonly isolated in HA-BSI. On multivariable analysis, severe underweight, severe anaemia at the time of BSI, admission in the ICU at the time of BSI, and requiring ICU admission after BSI was diagnosed were significantly associated with 14-day mortality. Conclusion: This study adds to the limited literature describing BSI in children in Africa. Further studies are required to understand the impact that BSI has on the paediatric population in sub-Saharan Africa.
- ItemOpen AccessCandida bloodstream infection among children hospitalized in three public sector hospitals in the Metro West region of Cape Town, South Africa(2022) Gebremicael, Mulugeta Naizgi; Eley, Brian; Nuttall, JamesIntroduction Candida bloodstream infection (BSI) causes appreciable mortality in children. There are few studies describing the epidemiology of Candida BSI in children living in the Western Cape province of South Africa. Methods A retrospective descriptive study was conducted at three public sector hospitals in Cape Town from January 2015 to December 2019. Demographic, clinical, antifungal management and patient outcome data were obtained by medical record review. Candida species and antifungal susceptibility results were extracted from the National Health Laboratory Service microbiology database Results Of the 97 Candida BSI episodes identified during the study period, 48/97 (49.5%) were C. albicans, 49/97 (50.5%) non-C. albicans species. The overall incidence risk was 0.84 Candida BSI episodes per 1000 admissions at Red Cross War Memorial Children's Hospital. Of the 77 Candida BSI episodes with available clinical information, median age (interquartile range) at the time of BSI was 6.8 (1.3-24.7) months, 46.8% were associated with moderate or severe underweight-for-age and vasopressor therapy was administered to 22 (28.6%) participants. Fluconazole resistance was documented among 25% and 0% of non-C. albicans and C. albicans isolates respectively. All Candida isolates tested were susceptible to amphotericin B and the echinocandins. The mortality rate within 30 days of BSI diagnosis was 17.3% (13/75). On multivariable analysis, concomitant bacterial infection during Candida BSI was associated with 30-day mortality, adjusted OR 5.7, 95% confidence interval: 1.4-24.0. Conclusion The study adds to the limited number of studies describing paediatric Candida BSI in sub Saharan Africa. Concomitant bacterial infection was associated with 30-day mortality.
- ItemOpen AccessCCL3L1 copy number, CCR5 genotype and susceptibility to tuberculosis(2014-01-09) Carpenter, Danielle; Taype, Carmen; Goulding, Jon; Levin, Mike; Eley, Brian; Anderson, Suzanne; Shaw, Marie-Anne; Armour, John AAbstract Background Tuberculosis is a major infectious disease and functional studies have provided evidence that both the chemokine MIP-1α and its receptor CCR5 play a role in susceptibility to TB. Thus by measuring copy number variation of CCL3L1, one of the genes that encode MIP-1α, and genotyping a functional promoter polymorphism -2459A > G in CCR5 (rs1799987) we investigate the influence of MIP-1α and CCR5, independently and combined, in susceptibility to clinically active TB in three populations, a Peruvian population (n = 1132), a !Xhosa population (n = 605) and a South African Coloured population (n = 221). The three populations include patients with clinically diagnosed pulmonary TB, as well as other, less prevalent forms of extrapulmonary TB. Methods and results Copy number of CCL3L1 was measured using the paralogue ratio test and exhibited ranges between 0–6 copies per diploid genome (pdg) in Peru, between 0–12 pdg in !Xhosa samples and between 0–10 pdg in South African Coloured samples. The CCR5 promoter polymorphism was observed to differ significantly in allele frequency between populations (*A; Peru f = 0.67, !Xhosa f = 0.38, Coloured f = 0.48). Conclusions The case–control association studies performed however find, surprisingly, no evidence for an influence of variation in genes coding for MIP-1α or CCR5 individually or together in susceptibility to clinically active TB in these populations.
- ItemOpen AccessThe clinical and molecular spectrum of galactosemia in patients from the Cape Town region of South Africa(BioMed Central Ltd, 2002) Henderson, Howard; Leisegang, Felicity; Brown, Ruth; Eley, BrianBACKGROUND:The objective of this study was to document the clinical, laboratory and genetic features of galactosemia in patients from the Cape Town metropolitan region. METHODS: Diagnoses were based on thin layer chromatography for galactosuria/galactosemia and assays of erythrocyte galactose-1-phosphate uridyltransferase (GALT) and galactokinase activities. Patients were screened for the common S135L and Q188R transferase gene mutations, using PCR-based assays. Screening for the S135L mutation in black newborns was used to estimate the carrier rate for galactosemia in black South Africans. RESULTS: A positive diagnosis of galactosemia was made in 17 patients between the years 1980 to 2001. All had very low or absent galactose-1-phosphate uridyltransferase (GALT) activity, and normal galactokinase levels. The mean age at diagnosis was 5.1 months (range 4 days to 6.5 months). A review of 9 patients showed that hepatomegaly (9/9), and splenomegaly, failure to thrive, developmental delay, bilateral cataracts (6/9) were the most frequent features at diagnosis. Six had conjugated hyperbilirubinemia. Four experienced invasive E. coli infection before diagnosis. Ten patients were submitted to DNA analysis. All 4 black patients and 2 of mixed extraction were homozygous for the S135L allele, while all 3 white patients were homozygous for the Q188R allele. The remaining patient of mixed extraction was heterozygous for the Q188R allele. The estimated carrier frequency of the S135L mutation in 725 healthy black newborns was 1/60. CONCLUSIONS: In the absence of newborn screening the delay in diagnosis is most often unacceptably long. Also, carrier frequency data predict a galactosemia incidence of approximately 1/14 400 for black newborns in the Cape Metropole, which is much higher than the current detection rate. It is thus likely that many patients go undetected.
- ItemOpen AccessColonisation with extended spectrum beta-lactamase producing and carbapenem-resistant enterobacterales in children admitted to a paediatric referral hospital in South Africa(2020) Ogunbosi, Babatunde Oluwatosin; Eley, Brian; Nuttall, JamesIntroduction: There are few studies describing colonisation with extended spectrum beta-lactamase-producing Enterobacterales (ESBL-PE) and carbapenem-resistant Enterobacterales (CRE) among children in subSaharan Africa. Colonisation often precedes infection and multi-drug-resistant Enterobacterales are important causes of invasive infection. Methods: In this prospective cross-sectional study, conducted between April and June 2017, 200 children in a tertiary academic hospital were screened by rectal swab for EBSL-PE and CRE. The resistance-conferring genes were identified using polymerase chain reaction technology. Risk factors for colonisation were also evaluated. Results: Overall, 48% (96/200) of the children were colonised with at least one ESBL-PE, 8 of these with 2 ESBLPE, and one with a CRE (0.5%, 1/200). Common colonising ESBL-PE were Klebsiella pneumoniae (62.5%, 65/104) and Escherichia coli (34.6%, 36/104). The most frequent ESBL-conferring gene was blaCTX-M in 95% (76/80) of the isolates. No resistance- conferring gene was identified in the CRE isolate (Enterobacter cloacae). Most of the Klebsiella pneumoniae isolates were susceptible to piperacillin/tazobactam (86.2%) and amikacin (63.9%). Similarly, 94.4% and 97.2% of the Escherichia coli isolates were susceptible to piperacillin/tazobactam and amikacin, respectively. Hospitalisation for more than 7 days before study enrolment was associated with ESBL-PE colonisation. Conclusion: Approximately half of hospitalised children in this study were colonised with ESBL-PE. This highlights the need for improved infection prevention and control practices to limit the dissemination of these microorganisms.
- ItemOpen AccessCulture-confirmed childhood tuberculosis in Cape Town, South Africa: a review of 596 cases(Biomed Central Ltd, 2007) Schaaf, H Simon; Marais, Ben; Whitelaw, Andrew; Hesseling, Anneke; Eley, Brian; Hussey, Gregory; Donald, PeterBACKGROUND:The clinical, radiological and microbiological features of culture-confirmed childhood tuberculosis diagnosed at two referral hospitals are described. METHODS: Cultures of Mycobacterium tuberculosis from children less than 13 years of age at Tygerberg and Red Cross Children's Hospitals, Cape Town, South Africa, were collected from March 2003 through February 2005. Folder review and chest radiography were performed and drug susceptibility tests done. RESULTS: Of 596 children (median age 31 months), 330 (55.4%) were males. Of all children, 281 (47.1%) were HIV-uninfected, 133 (22.3%) HIV-infected and 182 (30.5%) not tested. Contact with infectious tuberculosis adults was recorded in 295 (49.5%) children. Missed opportunities for chemoprophylaxis were present in 117/182 (64.3%) children less than 5 years of age.Extrathoracic TB was less common in HIV-infected than in HIV-uninfected children (49/133 vs. 156/281; odds ratio 0.50, 95% confidence interval 0.32-0.78). Alveolar opacification (84/126 vs. 128/274; OR 1.85, 95%CI 1.08-3.19) and cavitation (33/126 vs. 44/274; OR 2.28, 95%CI 1.44-3.63) were more common in HIV-infected than in HIV-uninfected children. Microscopy for acid-fast bacilli on gastric aspirates and sputum was positive in 29/142 (20.4%) and 40/125 (32.0%) children, respectively. Sixty-seven of 592 (11.3%) children's isolates showed resistance to isoniazid and/or rifampicin; 43 (7.3%) were isoniazid-monoresistant, 2 (0.3%) rifampicin-monoresistant and 22 (3.7%) multidrug-resistant. Death in 41 children (6.9%) was more common in HIV-infected children and very young infants. CONCLUSION: HIV infection and missed opportunities for chemoprophylaxis were common in children with culture-confirmed TB. With cavitating disease and sputum or gastric aspirates positive for acid-fast bacilli, children may be infectious. Transmission of drug-resistant TB is high in this setting.
- ItemOpen AccessEpidemiology of Staphylococcus aureus bacteraemia at a tertiary children's hospital in Cape Town, South Africa(Public Library of Science, 2013) Naidoo, Reené; Nuttall, James; Whitelaw, Andrew; Eley, BrianBACKGROUND: Staphylococcus aureus is an important pathogen in paediatric patients with bloodstream infections. The epidemiology of S. aureus bacteraemia, however, has not been well documented in children in South Africa. METHODS: A retrospective study was conducted at a children's hospital in Cape Town, South Africa, to investigate the epidemiology of S. aureus bacteraemia from 2007-2011. The incidence, clinical presentation, risk factors, management and outcomes of methicillin sensitive S. aureus (MSSA) and methicillin resistant S. aureus (MRSA) bacteraemia were compared. RESULTS: Over the five year study period, 365 episodes of S. aureus bacteraemia were identified. The annual incidence was 3.28 cases per 1000 hospital admissions. MRSA was responsible for 26% of S. aureus bacteraemia and 72% of nosocomial infections. Only six possible cases of community-acquired MRSA infections were described. MSSA bacteraemia was more likely to present as pulmonary and bone or joint infections, while bacteraemia without a source was the most common presentation with MRSA. Infants, children with malnutrition, and residents of long-term care facilities were at highest risk for MRSA bacteraemia. The overall case fatality rate for S. aureus bacteraemia was 8.8% over five years, with MRSA being the only significant risk factor for mortality. CONCLUSION: The incidence of S. aureus bacteraemia and MRSA bacteraemia in children has remained stable over the past five years. MRSA is a predominantly nosocomial pathogen in children with S. aureus bacteraemia in Cape Town, South Africa.
- ItemOpen AccessEpidemiology of Staphylococcus aureus bacteraemia at a tertiary children's hospital in Cape Town, South Africa(2012) Naidoo, Reené; Eley, Brian; Nuttall, JamesIncludes abstract. Includes bibliographical references.
- ItemOpen AccessGrowth of luciferase-transfected BCG in whole blood : use of a novel assay to study immune responses to mycobacteria in children(2003) Tena, Nontobeko Gwendoline; Henderson, Howard; Eley, Brian; Kampmann, BeateThe existing Bacille Calmette-Guerin (BCG) vaccine offers some protection against TB, but its efficacy varies for unknown reasons. In order to develop an effective vaccine, a comprehensive understanding of protective immunity in adults and children is needed. Studies involving host-pathogen interactions are complex and have been hampered by the slow growth of mycobacterial organisms.
- ItemOpen AccessGuidelines for the management of HIV-infected children (National Department of Health, South Africa, 2005): A summary of antiretroviral treatment guidelines(2005) Meyers, Tammy; Eley, BrianNational guidelines for the management of HIV-infected children in South Africa have been developed as a consensus document by practising HIV clinicians around the country. Guidelines for antiretroviral (ARV) management of children appear in a booklet distributed by the National Department of Health (DoH) since mid-2004 (National Antiretroviral Treatment Programme Guideline for Carers, National Department of Health, South Africa, 2004). A comprehensive booklet on management of HIV-infected children has also been produced for the DoH which includes recommendations on management with antiretroviral (ARV) therapy. The South African national paediatric guidelines are based on the recommendations provided by the World Health Organization (WHO) (Scaling up antiretroviral therapy in resource limited settings; treatment guidelines for a public health approach WHO 2003). It is important to note that WHO are updating their recommendations. Based on this some amendments, e.g. the staging system, have already been incorporated into the final version of the South African national guidelines. Other recommendations are more recent and have yet to undergo broader review. These have therefore not formed part of the printed version of the South African guidelines. It is anticipated that a process of updating the guidelines needs to be put in place urgently. The national guidelines are available on the government website (www.health.gov.za), and clinicians are advised to update themselves regularly at this website for any amendments that may be made to the guidelines.
- ItemOpen AccessHIV Encephalopathy: pediatric case series description and insights from the clinic coalface(BioMed Central, 2015-01-17) Donald, Kirsten A; Walker, Kathleen G; Kilborn, Tracy; Carrara, Henri; Langerak, Nelleke G; Eley, Brian; Wilmshurst, Jo MBackground: The Human Immune Deficiency Virus (HIV) can manifest neurologically in both adults and children. Early invasion of the central nervous system by the virus, affecting the developing brain, is believed to result in the most common primary HIV-related neurological complication, HIV Encephalopathy (HIVE). In countries such as South Africa where many children have not been initiated on antiretroviral treatment early, HIVE remains a significant clinical problem. Methods: Children were selected from a clinic for children with neurologic complications of HIV, located at the Red Cross War Memorial Children’s Hospital, South Africa 2008–2012. Eligible subjects fulfilled the following inclusion criteria: aged 6 months-13 years; positive diagnosis of HIV infection, vertically infected and HIVE as defined by CDC criteria. Each participant was prospectively assessed by a Pediatric Neurologist using a standardized proforma which collated relevant details of background, clinical and immunological status. Results: The median age of the 87 children was 64 months (interquartile range 27–95 months). All except one child were on antiretroviral treatment, 45% had commenced treatment <12 months of age. Delayed early motor milestones were reported in 80% and delayed early speech in 75% of children in whom we had the information. Twenty percent had a history of one or more seizures and 41% had a history of behavior problems. Forty-eight percent had microcephaly and 63% a spastic diplegia. CD4 percentages followed a normal distribution with mean of 30.3% (SD 8.69). Viral loads were undetectable (
- ItemOpen AccessHIV-infected infants born to women who tested HIV-negative during pregnancy(2004) Nuttall, James; Eley, Brian; Honikman, SimoneThe prevention of mother-to-child transmission (PMTCT) programme in the Western Cape is said to have achieved 100% coverage.1 This implies that all pregnant women who attend an antenatal health care facility in the public sector are offered voluntary counselling and testing (VCT). Uptake varies but has been reported to be as high as 90% in the Guguletu district.1 Currently, women who test HIV-positive qualify for the nevirapine-based PMTCT programme. Transmission rates below 10% have been achieved in some health districts (Médecins sans Frontières — unpublished research). Mothers of several perinatally infected infants recently diagnosed in our institution have indicated that they tested HIV-negative during their pregnancy. In some cases we have verified their statements with clinical and laboratory documentation. There is a need to determine the frequency of this phenonomen. Pregnant women are encouraged to book at their nearest antenatal clinic before 5 months’ gestation, although this frequently does not occur. We are concerned about women who do book early and test HIV-negative. Some may be in the ‘window period’ of the infection or become infected from a sexual partner during the latter stages of pregnancy. At present, there is no provision within the PMTCT programme for repeat HIV testing during pregnancy. Some women may, therefore, be denied the benefits of prevention measures including counselling on infant feeding options.
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