title: Low prevalence of Pneumocystis pneumonia (PCP) but high prevalence of pneumocystis dihydropteroate synthase (dhps) gene mutations in HIV-infected persons in Uganda.
abstract: 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 newly-diagnosed 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.
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, United States of America. taylo115@email.unc.edu
authors.forename: Steve M
authors.initials: SM
authors.lastname: Taylor
authors.forename: Steven R
authors.initials: SR
authors.lastname: Meshnick
authors.forename: William
authors.initials: W
authors.lastname: Worodria
authors.forename: Alfred
authors.initials: A
authors.lastname: Andama
authors.forename: Adithya
authors.initials: A
authors.lastname: Cattamanchi
authors.forename: J Lucian
authors.initials: JL
authors.lastname: Davis
authors.forename: Samuel D
authors.initials: SD
authors.lastname: Yoo
authors.forename: Patrick
authors.initials: P
authors.lastname: Byanyima
authors.forename: Sylvia
authors.initials: S
authors.lastname: Kaswabuli
authors.forename: Carol D
authors.initials: CD
authors.lastname: Goodman
authors.forename: Laurence
authors.initials: L
authors.lastname: Huang
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000453:epidemiology / Q000235:genetics*; D001399:Azure Stains; D001483:Base Sequence; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology; D004094:Dihydropteroate Synthase / Q000235:genetics*; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics; D045363:Pneumocystis carinii / Q000201:enzymology*; D011020:Pneumonia, Pneumocystis / Q000453:epidemiology*; D016133:Polymerase Chain Reaction; D015995:Prevalence; D017422:Sequence Analysis, DNA; D018709:Statistics, Nonparametric; D014454:Uganda / Q000453:epidemiology
chemical_list: D001399:Azure Stains; D004094:Dihydropteroate Synthase