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A Study of Pneumocystis Pneumonia in South Africa
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A Study of Pneumocystis Pneumonia in South Africa
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Dissertation
A Study of Pneumocystis Pneumonia in South Africa
2011
Overview
An increased prevalence of Pneumocystis jirovecii with point mutations in the fas gene, coding for dihydropteroate synthase (DHPS), has been associated with sulfonamide use. The purpose of this research was to investigate the prevalence of P. jirovecii strains containing DHPS polymorphisms in South Africa, and to ascertain their clinical relevance in HIV-positive patients with Pneumocystis pneumonia (PCP). A pilot study confirmed the presence of DHPS polymorphisms in 42% of specimens. A subsequent prevalence study confirmed the high prevalence (56%) of mutant P. jirovecii in adult patients. A prospective clinical study found that 61% of PCP patients were infected with mutant P. jirovecii. The overall in-hospital mortality was 21%. Significantly more patients died in hospital of mutant P. jirovecii than those infected with wild-type strains (P= 0.04). Mortality at three months among the discharged patients was associated with the wild-type genotype. However, cause of death was unknown. There were no significant associations in patients infected with P. jirovecii containing single DHPS mutations versus those infected with the M3 genotype. There was an insignificant trend for patients infected with M3 strains to have lower median CD4+cell counts versus patients harbouring single mutant strains (P= 0.06). Few patients were exposed to sulfonamides and 58% of patients diagnosed with HIV on admission harboured mutant P. jirovecii. P. jirovecii strains, in a subset of clinical study patients, were characterized by ITS typing. Eleven bona fide ITS haplotypes, six ITS1 and nine ITS2 types, were found. Almost half of the patients harboured more than one P. jirovecii strain. Eg occurred at a high frequency of 85%, and the presence of the local South African haplotype Eu was confirmed. Other ITS haplotypes detected were: Em, Ec, Eb, Bi, Gg, Ep, Fu4, Ne and Ai. Two novel ITS1 sequences SA1 and SA2 were detected. There were no obvious associations between ITS haplotype and a particular clinical characteristic or outcome. Eg haplotypes were more often associated with a wild-type DHPS genotype. Inter-human transmission of P. jirovecii carrying mutant DHPS genotypes could, at least in part, explain the high prevalence of DHPS mutations in adult HIV-positive South Africans.
Publisher
ProQuest Dissertations & Theses
Subject
ISBN
9798302104694
