3. Electronic Theses and Dissertations (ETDs) - All submissions
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Item Epidemiology of childhood pneumonia in the era of antiretroviral therapy and bacterial conjugate vaccines(2018) Moore, David PaulBackground, Pneumonia is the leading non-neonatal cause of under-5 death globally, and in South Africa. Human immunodeficiency type 1 (HIV)-infection and -exposure are risk factors for pneumonia in children. Aim We appraised the aetiology of under-5 pneumonia in the era of access to bacterial conjug ate vaccines targeting Haemophilus influenzae type b and Streptococcus pneumoniae and well functioning prevention of mother-to-child transmission and antiretroviral treatment (ART) programmes to prevent and treat paediatric HIV infection. Methods, This research was conducted within the framework of the Pneumonia Etiology Research for Child Health (PERCH) study, at the South African PERCH site (Chris Hani Baragwanath Academic Hospital, Soweto, Gauteng Province). Cases, aged 1-59 months hospitalised with World Health Organization-defined severe or very severe pneumonia (according to pre-2012 definitions) from mid-August 2011 through end-August 2013 were compared to age-frequency, HIV-status matched controls. The aetiologic fraction of pneumonia attributed to each potential pathogen was calculated through comparison of nasopharyngeal-oropharyngeal (NP/OP) swab and whole blood PCR results, using conditional logistic regression. Results' Pneumonia incidence (per 100 000 children) was 1 755.00 (95% CI, 1 701.8 to 1 809.5) overall, highest in younger children, HIV-infected and HIV-exposed, uninfected (HEU) children. Respiratory viruses contributed 0.59 (95% CI, 0.47-0.62) of the ‘fraction of association’ (FA) with radiologically-confirmed pneumonia, whereas bacteria were associated with 0.29 (95% CI, 0.18-0.35) in the cohort. Respiratory viruses predominated in HEU (FA 0.53; 95% CI, 0.39-0.58) and HIV-unexposed children (FA 0.57; 95% CI, 0.43-0.61). Opportunistic pathogens (human cytomegalovirus (CMV) and Pneumocystis jirovecii) were the predominant organisms in HIV-infected children (FA 0.58; 95% CI, 0.38-0.65). Respiratory syncytial virus (RSV) was the most important organism associated with case-status in HIV-uninfected children (FA 0.31; 95% CI, 0.30-0.32) and HIV-infected children on ART (FA 0.21; 95% CI, 0.16-0.21). CMV, P. jirovecii and Klebsiella spp. were identified as being the pathogens most frequently associated with death in children that underwent lung biopsy. Conclusion, Strategies to shorten antibiotic therapy in HIV-uninfected children hospitalised with pneumonia may enhance antibiotic stewardship at the study site. Continued efforts at expediting initiation onto ART in HIV-infected children would likely impact favourably on the burden of opportunistic infection-associated pneumonia and its attendant mortality. Research into vaccination against RSV and CMV is a priority.Item Defining the burden of pulmonary tuberculosis and probing the prevalence of pneumococcal bacterial co-infections among children hospitalised with pulmonary tuberculosis that were enrolled in a pneumococcal vaccine trial(2010-01-29T10:32:57Z) Moore, David PaulBackground In settings with a high burden of tuberculosis, children with unrecognised culture-confirmed pulmonary tuberculosis (PTB) may be discharged from hospital before mycobacterial culture results are available; in these cases clinical improvement may have been due to successful treatment of an intercurrent viral or bacterial co-infection. Aim To estimate the burden of tuberculosis in children who were enrolled in a double-blind, placebo-controlled pneumococcal conjugate vaccine (PCV) trial, and to probe for the presence of pneumococcal co-infection in trial participants who had a hospital-based diagnosis of PTB. Methods A retrospective case-finding strategy was adopted in order to define the tuberculosis case load amongst 39 836 children that had been enrolled in a PCV efficacy trial in Soweto, Gauteng Province. The trial follow-up period was 5.3 years. Children with a hospital-based diagnosis of tuberculosis were categorised by strength of evidence for the disease, HIV status and PCV vaccination status. Incidence rates and risk ratio assessments were conducted using standard statistical methods. Results Four-hundred and ninety-two episodes of tuberculosis arose amongst 425 of the 39 836 PCV Study participants. Tuberculosis incidence was 1067 per 100 000 children (95% Confidence Interval [CI], 968 – 1173), with the greatest burden observed amongst HIV-infected children (10 633 per 100 000 children [95% CI, 9411 – 11 969]; Risk Ratio [RR] 27.5 [95% CI, 22.6 – 33.5], P<0.001). The burden of PTB in the cohort was 982 cases per 100 000 children (95% CI, 887 – 1084): 9895 per 100 000 (95% CI, 8718 – 11 187) in the HIV-infected children and 352 per 100 000 (95% CI 294 – 417) in the HIV-uninfected children (RR 28.1; 95% CI, 22.9 – 34.6), P<0.001. PCV recipients exhibited a 44 percent (95% CI, 11 – 65), P=0.010, reduction in incident culture-confirmed PTB compared to placebo recipients; this apparent reduction was demonstrated chiefly in PCV-vaccinated HIV-infected children (RR 0.53; 95% CI, 0.31 – 0.90) compared to HIV-infected placebo recipients, P=0.017. Conclusions A high burden of tuberculosis is carried by children under 5.3 years in the study setting, with HIV-infected children bearing the brunt of the morbidity. Pneumococcal co-infections are common in the context of hospitalised PTB in the study setting.