Title Low Prevalence of Pneumocystis pneumonia ( PCP ) but High Prevalence of Pneumocystis dihydropteroate synthase ( dhps ) Gene Mutations in HIV-Infected Persons in Uganda Permalink

Pneumocystis jirovecii pneumonia (PCP) is an important opportunistic infection in patients infected with HIV, but its burden is incompletely characterized in those areas of sub-Saharan Africa where HIV is prevalent. We explored the prevalence of both PCP in HIV-infected adults admitted with pneumonia to a tertiary-care hospital in Uganda and of putative P. jirovecii drug resistance by mutations in fungal dihydropteroate synthase (dhps) and dihydrofolate reductase (dhfr). In 129 consecutive patients with sputum smears negative for mycobacteria, 5 (3.9%) were diagnosed with PCP by microscopic examination of Giemsa-stained bronchoalveolar lavage fluid. Concordance was 100% between Giemsa stain and PCR (dhps and dhfr). PCP was more prevalent in patients newly-diagnosed with HIV (11.4%) than in patients with known HIV (1.1%; p = 0.007). Mortality at 2 months after discharge was 29% overall: 28% among PCP-negative patients, and 60% (3 of 5) among PCP-positive patients. In these 5 fungal isolates and an additional 8 from consecutive cases of PCP, all strains harbored mutant dhps haplotypes; all 13 isolates harbored the P57S mutation in dhps, and 3 (23%) also harbored the T55A mutation. No non-synonymous dhfr mutations were detected. PCP is an important cause of pneumonia in patients newlydiagnosed with HIV in Uganda, is associated with high mortality, and putative molecular evidence of drug resistance is prevalent. Given the reliability of field diagnosis in our cohort, future studies in sub-Saharan Africa can investigate the clinical impact of these genotypes. Citation: Taylor SM, Meshnick SR, Worodria W, Andama A, Cattamanchi A, et al. (2012) Low Prevalence of Pneumocystis pneumonia (PCP) but High Prevalence of Pneumocystis dihydropteroate synthase (dhps) Gene Mutations in HIV-Infected Persons in Uganda. PLoS ONE 7(11): e49991. doi:10.1371/journal.pone.0049991 Editor: Ana Paula Arez, Instituto de Higiene e Medicina Tropical, Portugal Received May 15, 2012; Accepted October 19, 2012; Published November 16, 2012 Copyright: 2012 Taylor et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by the National Heart, Lung, and Blood Institute [K24 HL087713 and R01 HL090355 to L.H.] and by the National Institute of Allergy and Infectious Diseases [K23 AI080147 to JLD]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: taylo115@email.unc.edu " Membership of the International HIV-associated Opportunistic Pneumonias (IHOP) Study is provided in the Acknowledgments.