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A thesis submitted to the Faculty of Health Sciences, University of the Witwatersrand, in fulfilment of the requirements for the degree of Doctor of Philosophy / Background Silicosis rates in gold miners in South Africa are very high but there have been no analyses of long term trends. While much research has been conducted on occupational respiratory disease in gold, asbestos and coal miners, little is known about the respiratory health of miners of other commodities, such as diamonds and platinum, two of the most important minerals in South Africa. The ore bodies from which minerals are mined often contain other „incidental‟ minerals and compounds that may cause disease. Aims The aims of this thesis were to conduct the first ever analysis of silicosis trends in black and white gold miners over a 33-year period; to discuss the role of oscillating migration in the high rates of silicosis; and to explore the potential for workers in the diamond and platinum mining sectors to develop occupational respiratory diseases. Methods Gold, diamond and platinum mine workers were identified from the PATHAUT autopsy database at the National Institute for Occupational Health. Trends in silicosis from 1975 to 2007 were calculated separately for black and white gold miners because of differences in exposure, patterns of employment and autopsy referral patterns. The role of oscillating migration in the silicosis epidemic was explored. Diamond mine workers with asbestos-related diseases at autopsy and platinum mine workers with silicosis and/or fibrotic nodules in the lymph nodes were identified. Supplementary data from other sources were reviewed to viii exclude all those who might have been exposed to asbestos or silica, respectively, outside of the mining sector in which they worked. Asbestos lung burdens were calculated for the case series of diamond miners and mine tailings and soil samples were examined for asbestos fibres, using scanning electron microscopy. Findings The proportion of white miners with silicosis increased by 17% (from 18% to 22%) over the 33-year study period. That of black miners increased 10-fold (from 3% to 32%), primarily due to the aging workforce and increasing periods of employment. Adjusted odds ratios for silicosis increased with year of autopsy for black miners. Oscillating migration has also played a major role in the silicosis epidemic. Evidence indicates that diamond mine workers are at risk for developing asbestosrelated diseases and that platinum mine workers are at risk for developing silicosis. Conclusion The gold mines have failed to control silica dust levels adequately and prevent disease in mine workers. The sparsity of available dust measurements and poorly documented work histories are major obstacles to conducting occupational health research in South Africa; attention and legislation needs to be focused urgently on these areas. The PATHAUT database is the only occupational respiratory disease database in South Africa that can be used for disease surveillance, trend analyses and research in all mining sectors.

Background: Lower respiratory tract infections (LRTI) are a leading cause of morbidity and mortality in young children. A number of new viruses associated with LRTI in young children have recently been discovered. These include Human Bocavirus (HBoV), Human Polyomavirus strains WU (WUPyV) and KI (KIPyV) and Human Coronavirus strains NL63 (HCoV-NL63) and HKU-1 (HCoV-HKU-1). There is, however, limited data on the epidemiology of these newly discovered respiratory viruses in industrializing country settings, including South Africa. Objective: To determine the clinical epidemiology of HBoV, HCoV-NL63, HCoVHKU1, HCoV-OC43, HCoV strain 229E (HCoV- 229E), WUPyV, KIPyV and human rhinovirus (HRV) in young children. Methods: Nasopharyngeal aspirates where taken from children who were hospitalized at Chris Hani Baragwanath Hospital between February 2000 and January 2002 with severe LRTI. These children had been enrolled in a double-blind, randomized, placebo-controlled trial of a 9-valent pneumococcal conjugate vaccine (PCV). Nucleic acid extraction was undertaken from archived nasopharyngeal aspirate samples and the respiratory viruses identified using real time duplex PCR. The study was limited to examining samples from HIV uninfected children with LRTI who were less than 24 months of age. Results: Overall, samples were available for 895 of 1565 nasopharyngeal aspirates, from children hospitalized with LRTI, collected from February 2000 to January 2002. A comparison between those LRTI episodes for which samples were unavailable compared to those for which samples were available indicated that children in whom samples were unavailable were younger than children with available samples (9.9±6.4 vs. 11.8±6.5 months; p<0.0001). In addition there was a higher frequency of wheezing episodes in children for whom samples were unavailable (60.4 vs. 54.6%; p=0.022). The overall prevalence of the viruses in children with any LRTI were 33.2% for HRV, 21.2% for HBoV, 16.1% for WUPyV, 10.1% for HCoV-OC43, 7.0% for KIPyV, 3.2% for HCoVNL63, 2.6% for HCoV-HKU-1, and 0.6% for HCoV-229E. There was a higher probability of detecting a selected virus in LRTI episodes among PCV-compared to placebo-recipients for HBoV (24.2% vs. 18.2%, respectively; p=0.028) and HRV (36.7% vs. 29.5%, respectively; p=0.023). Conversely, viruses identified more frequently in LRTI episodes among children who received placebo compared to PCV-recipients included WUPyV (20.2% vs. 12.1%, respectively; p=0.001), KIPyV (10% vs. 4.2%, respectively; p=0.001), HCoV-OC43 (14.1% vs. 6.2%, respectively; p≤0.0001) and HCoV-HKU1 (4.5% vs. 0.1%, respectively; p≤0.0001). Overall, the prevalence of the studied-viruses in the subgroup of children categorized as having bronchiolitis was 33.8% for HRV, 33.4% for WUPyV, 22.3% for HBoV, 11.1% for HCoVOC43, 5.3% for KIPyV, 2.3% for HCoV-NL63, 1.9% for HCoV-HKU1 and 0.4% for HCoV-229E. Viruses more commonly identified in placebocompared to PCV-recipients among children hospitalized with bronchiolitis included WUPyV (20.0% vs. 12.3%, respectively; p=0.029), HCoV-OC43 (15.9% vs. 7.2%, respectively; p=0.004) and HCoV-HKU1 (3.6% vs. 0.5%, respectively; p=0.015). The prevalence of the newly studied viruses in the subgroup of children categorized as having clinical pneumonia was 30.8% for HRV, 20.3% for HBoV, 16.4% for WUPyV, 9.1% for HCoVOC43, 8.6% for KIPyV, 4.1% for HCoV-NL63, 3.2% for HCoV-HKU1 and 0.6% for HCoV-229E. Viruses identified more frequently among placebo- compared to PCV-recipients, in those with clinical pneumonia, included WUPyV (20.4% vs. 11.9%, respectively; p=0.013),HCoV-HKU1 (5.3% vs. 0.9%, respectively; p=0.008). Conversely, HCoV-OC43 was identified more frequently in children with clinical pneumonia among PCV- (5.0%) compared to placebo-recipients (2.7%, p=0.004). There were seasonal peaks, during autumnwinter months (April to June), in the detection of HRV, WUPyV, HCoV-OC43, HCov-NL63 and HCoV-HKU1, whereas KIPyV, HBoV and HCoV- 229E were identified perennially. Conclusion: Prevalence of respiratory viruses is high in industrializing countries and the presence of these viruses is frequently associated with co-infections of more than one etiological agent. In industrializing countries such as in South Africa, the recently identified respiratory viruses play a role in development of pneumonia. KIPyV (12.7% vs. 4.1%, respectively; p=0.001),