3. Electronic Theses and Dissertations (ETDs) - All submissions
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Item Role of molecular evolution in respiratory syncytial virus antigenic proteins during annual epidemics in South Africa(2004-05-28) Agenbach., Elizabeth.Respiratory syncytial virus (RSV) is a major cause of pneumonia in children worldwide and there is currently no vaccine available. Molecular analysis of annual RSV epidemics in Soweto (1997 to 2000), revealed co-circulation and displacement of dominant genotypes. However in 1999 to 2000, one genotype GA2, predominated. To further elucidate the molecular epidemiology of RSV in South Africa the 2001 RSV epidemic in Soweto was characterised. Phylogenetic analysis of the G-protein revealed subtype B dominance (89%). Sequences clustered in genotypes GA2, GA5, SAA1, GB3, SAB1 and SAB3. SAB3 dominanted (69%) followed by SAB1 (18%), thereby displacing GA2, which dominated the previous two seasons. Evidence of positive selection may account for the genetic variability observed and may contribute to the reestablishment of annual epidemics. To investigate if this influences evolution of other RSV antigenic proteins the F-protein of South African genotypes was characterised. Most amino acid differences identified within known neutralising and CTL epitopes were conserved within subtype A, and although this does not suggest immune selection these epitopes may not be recognised efficiently by antibodies or CTL specific to subtype B virusesItem The impact of haemophilus influenzae type b (hib) vaccine on pneumonia and meningitis among children under the age of 1 year in the Klerksdorp district of the North West Province(2000-11-07) Sebekedi ( Nee Mhele), Otsile, CalviniaThe purpose of this study was to determine the impact of Hib vaccine on pneumonia and meningitis in children under the age of 1 year in the Klerksdorp district of the North West Province.Item Patient characteristics and determinants of outcomes of children admitted with pneumonia to a Paediatric Intensive Care Unit (SLE) in a Tertiary Hospital in Johannesburg(2017) Keeling, Kathryn HelenBackground. Pneumonia is the leading infectious cause of death worldwide. HIV infected and exposed children are at greater risk for developing pneumonia. HIV exposed infants have been said to have a worse outcome than their HIV unexposed counterparts. Objectives. To describe the patient characteristics and determinants of the outcome of children admitted to the paediatric intensive care unit (PICU) with pneumonia. Methods. This was a retrospective review of patients admitted to a PICU between 1 January 2013 and 31 December 2014. Results. One hundred and seven patients were analyzed, of these 65.4% had a normal weight for age. Fifty percent of patients were HIV unexposed, 21.5% HIV infected and 26.2% HIV exposed but uninfected. The HIV infected group had a significantly longer length of stay (p= .011), duration of ventilation (p= .003) and higher mortality (p= .014) when compared to the HIV uninfected group. Likewise compared to HIV exposed but uninfected children, HIV infected had a longer length of stay (p=. 006), duration of ventilation (p= .003) and a greater mortality (p= .038). When the oxygenation index is ≥16, patients had a longer duration of ventilation (p= .037) and they had an increased risk of mortality (p< .001) Multiple regression showed that oxygenation index was the only significant predictor of death. Conclusion. HIV infected children had a significantly higher mortality than both HIV uninfected and HIV exposed but uninfected children. An oxygenation index of greater than 16 is a significant predictor for longer duration of mechanical ventilation and death.Item Microbial aetiology of community acquired pneumonia at a tertiary institution in Johannesburg, South Africa(2015-03-27) Meiday, ParastuIntroduction To determine the spectrum of aetiological agents in adult Community Acquired Pneumonia (CAP) admitted to an academic hospital in Johannesburg using a novel transport medium (PrimeStore™ MTM), in addition to traditional specimen processing. PrimeStore™ MTM preserves released nucleic acids, including labile RNA. Materials and Methods Forty-eight adult patients with radiologically confirmed CAP were prospectively studied over three months. Microbiological investigation included culture from blood and sputum, with pulmonary tuberculosis being excluded by sputum microscopy and culture. Nasopharyngeal swabs (PrimeStore™ MTM) were analysed using two commercial multiplex PCR assays for the detection of 6 major bacteria and 12 major respiratory viruses. The BinaxNOW Legionella urinary antigen test was also used. Results A probable microbial aetiology of CAP was established for 62.5% (30 of the 48 patients) when the PCR platform was added to the conventional methods with the use of the PrimeStore™ MTM swabs. In contrast, the definite bacterial aetiology was 16.7% (8 of 48 patients) when conventional culture methods were used; none had more than one bacterial species identified. Five patients had no aetiological pathogens determined. The urine Legionella pneumophila antigen was negative in all patients. Of the eight patients (16.7%) with a definite bacterial aetiology; Streptococcus pneumoniae was isolated from blood cultures of all eight patients.Item Cryptococcal antigenaemia in patients hospitalised with community acquired pneumonia at Chris Hani Baragwanath Academic Hospital(2014-08-27) Korb, AnneliBackground Cryptococcus is a life-threatening opportunistic infection; data is limited regarding early infection. Treatment of cryptococcal antigenaemia may impact on disease progression. Screening those most at risk for cryptococcal antigenaemia is necessary to be cost effective. The prevalence of cryptococcal antigenaemia in patients hospitalised with community acquired pneumonia (CAP) at Chris Hani Baragwanath Academic Hospital (CHBAH) was evaluated. Methods 200 patients admitted to CHBAH with presumed CAP were enrolled. Clinical and laboratory data were collected and a Cryptococcal Lateral Flow Immunoassay was done on whole blood. Results Of the 200 patients, 185 (92.5%) were HIV-infected. Amongst the HIV-infected group, the median CD4 cell count was 47 cells/mm3 and 111 subjects (60%) had a CD4 cell count < 100 cells/mm3. The prevalence of cryptococcal antigenaemia was 0.5% (CI 0.01-2.75). Conclusion The prevalence of cryptococcal antigenaemia amongst inpatients with CAP was low. Routine screening of this group would not be cost-effective.Item Resolution of mixed dihydropteroate synthase (DHPS) genotypes in respiratory specimens from patients with Pneumocystis jirovecci pneumonia from Gauteng, South Africa(2012-06-20) Poonsamy, BhavaniPneumocystis pneumonia (PCP) is one of the most prevalent diseases in HIV-positive and other immunosuppressed patients. It is caused by the opportunistic fungal pathogen Pneumocystis jirovecii. Dihydropteroate synthase (DHPS) mutations in P. jirovecii have been linked to resistance to trimethoprim-sulphamethoxazole (cotrimoxazole), the main treatment and prophylaxis used for PCP. DHPS mutations have been identified globally, predominantly in developed countries. This study investigated the P. jirovecii DHPS genotypes in PCP-positive patients from Chris Hani Baragwanath Hospital in Gauteng Province, South Africa. During the period March 2005 through June 2009, 266 patients were enrolled in the study and 306 specimens were collected. P. jirovecii was identified in 67% (205/306) of these specimens with quantitative real-time PCR (qPCR). The qPCR had a sensitivity of 98% and a specificity of 70%, compared with the immunofluorescence assay (IFA). Using sequencing and cloning techniques, 64% (110/173) of the nested PCR-positive specimens contained P. jirovecii with mutant DHPS genotypes. There was no association between patients harbouring P. jirovecii with mutant DHPS genotypes and in-hospital patient outcome (p-value = 0.19). As part of this project the Roche MagNA Pure Compact (RMPC) instrument and technology was validated for use as a new DNA extraction method. The RMPC was quick and easy to use compared to the Qiagen manual extraction method. The specificity of the qPCR was compromised by the high number of apparent false positive results obtained by the assay. However, as the IFA is an imperfect gold standard, these are probably true cases of infection or colonisation. This study found a higher proportion of P. jirovecii with DHPS mutant genotypes than wild type in PCP patients, which is unusual. The most probable reason for this is the widespread use of sulfa drugs, which are thought to select for these mutations. While this study did not find an association between DHPS mutations and adverse patient outcome, there have been contradictory findings. If further investigations reveal that DHPS mutations affect patient treatment or outcome, it will have major implications for the management of PCP in the country.Item The use of the CRB-65 severity of illness score to determine the need for admission of patients with community-acquired pneumonia presenting to an emergency department(2012-01-17) Kabundji, Dalton MulombeIntroduction: The decision as to the most appropriate site of care of a patient with community-acquired pneumonia (CAP), especially whether hospitalisation is warranted or not, is one of the most important decisions in the overall emergency department management of such patients. It has consequences both with regard to the level of treatment received by the patient as well as the overall costs of treatment. Several tools have been developed to predict mortality and/or determine which patients could be sent home and treated safely with good clinical outcomes. The CRB-65 score is one of the validated severity of illness scoring tools recommended. This scoring system may be of particular benefit in resourceconstrained areas, as it is easier to use. Study’s aim: To determine whether it would be useful to introduce the CRB-65 severity of illness score in the routine evaluation of patients with CAP in the Helen Joseph Hospital Emergency Department (HJH ED). Study’s objectives: To determine what criteria HJH ED doctors use in their decision to admit or discharge CAP patients; to determine the frequency with which the CRB-65 severity of illness score is used in current practice by the HJH ED doctors for admitting or discharging CAP patients; and to determine the potential performance of the CRB-65 severity of illness score in the management of patients with CAP in the HJH ED. Design: Prospective, observational, hospital-based study.Patients and methods: All patients 18 years of age and older with the diagnosis of CAP constituted our study population. Data from 152 patients seen between February 2011 and April 2011 was collected and analysed. Outcome measures included hospital admission or discharge, time to clinical stability, length of hospital stay, and mortality. Results: Overall, 152 patients (79 females and 73 males) were included in the analysis. The median age was 36.5 years, with a range from 20 to 87 years. The chest radiograph was the commonest criterion (41%) used by the HJH ED doctors to determine the need for admission of the patients with CAP, while the haemodynamic parameters were the commonest criteria used (25.9%) for discharge decisions. On only three occasions was the CRB-65 score utilised out of the 193 criteria documented (1.55%). There was a significantly shorter time to clinical stability (p = 0.0069), but no tendency to a shorter length of hospital stay in patients with a lower CRB-65 score (p = 0.5694). Patients with a higher CRB-65 score were at significantly higher risk of death compared to patients with a lower CRB-65 score (p < 0.001). There were no deaths from outpatients, but there were a total of five deaths observed from the inhospital patients of which 3/5 patients (60%) would potentially have been classified as intermediate mortality risk and the remaining 2/5 patients (40%) as high mortality risk if the CRB-65 score had been the only criterion used as the standard for site of care decisions by the HJH ED doctors. Conclusion: The chest radiograph was the commonest criterion used by the HJH ED doctors to determine the need for admission of the patients with CAP, while the haemodynamic parameters were the commonest criteria used for discharge decision. The CRB-65 score is not frequently being used in current practice by the HJH ED doctors for admitting or discharging CAP patients. This study demonstrates the ability of the CRB-65 severity of illness score to accurately predict both the time to clinical stability for patients hospitalised with CAP and the risk of death associated. In addition, this study documents that the CRB-65 severity of illness score performed well in its ability to determine the initial site of care for patients with CAP. Setting: Emergency Department of the Helen Joseph Hospital.Item Molecular epidemiology and clinical characteristics of the human metapneumovirus in South Africa(2008-03-19T10:17:51Z) Ludewick, Herbert PatrickIV. ABSTRACT The human metapneumovirus is a novel paramyxovirus associated with acute respiratory infections in children, adults, elderly and immunocompromised individuals. It has a worldwide distribution and the prevalence range between 1.5% to 25% in individuals with respiratory infections. Based on phylogenetic analysis 2 distinct genetic groups (A and B) that are sub-divided into four subgroups (A1, A2, B1 and B2) have been shown to circulate. Until recently, there was no information on the molecular epidemiology and the clinical characteristics of the hMPV in Africa, including South Africa, a region with a high prevalence of paediatric human immunodeficiency virus type-1 (HIV) infection. The molecular epidemiology and clinical characteristics of the hMPV in South Africa was investigated over a three period (2000-2002) in children hospitalized with lower respiratory tract infection. The children were part of a cohort participating in a phase 3 clinical trial investigating the efficacy of a 9-valent-pneumocococcal protein-polysaccharide conjugate vaccine (PCV). The objectives of the study were: i. to investigate the molecular epidemiology of hMPV in South Africa; ii. characterize the burden of hMPV disease and determine the clinical features of hMPV-LRTI in children infected and not infected by HIV; iii. probe the role of Streptococcus pneumoniae in the pathogenesis of hMPV-LRTI. The overall prevalence of hMPV in children hospitalized with lower respiratory tract infections (LRTI) was 7.4%. The mean age of children with hMPV associated LRTI (hMPV-LRTI) in South Africa was 13.3 months (range 1.4-49.2 months), with HIV infected children being older than children not infected with HIV (mean [range] 17.6 [4.5-44.3] vs. 12.3 [1.4-49.2] months; P=0.007). The incidence of hMPV-LRTI was 5.0 (95%C.I.3.3-7.5) fold greater in HIV infected children (incidence rate: 2 504 [95%C.I. 1 683-3 577] per 100 000) than in HIV uninfected children (incidence rate: 505 [95%C.I. 409-618] per 100 000, P<0.0001). Human metapneumovirus was identified less frequently than RSV but more commonly than other studied respiratory viruses. The double-blind PCV-9 vs. placebo controlled trial was used to probe the role of pneumococcal co-infections contributing to the pathogenesis of severe hMPV-LRTI. The incidence of hospitalization for hMPV-LRTI was reduced by 46% (95%, CI, 25-63; P=0.0002) in PCV-9 vaccinees compared to placebo recipients. This inferred that coinfection with Streptococcus pneumoniae was integral to the pathogenesis of hMPV-LRTI requiring hospitalization. Both groups of the hMPV circulated during the three year period including concurrent circulation of multiple subtypes of the virus. There was a transition from group B to group A subtype virus as the dominant circulating virus over sequential years. Sequence analysis of the two attachment glycoproteins (F and G), showed the F gene protein to be highly conserved, in contrast the attachment protein gene (G protein) was highly variable particularly in the extracellular domain between lineages. Repeat hMPV-LRTI by either homologous or heterologous strains within 3 months of each other suggested that natural infection did not confer complete immunity to hMPV. The present study demonstrated that hMPV is a leading pathogen associated with LRTI among children in Africa and indicated that occult pneumococcal co-infections’ were integral in the pathogenesis of hMPV-LRTI requiring hospitalization. Additionally, this is the first study to have characterized the molecular epidemiology of hMPV in Africa and provides insight as to issues that may exist regarding the design of an hMPV vaccine.