Severity and outcome of HIV-associated Pneumocystis pneumonia containing Pneumocystis jirovecii dihydropteroate synthase gene mutations.

BACKGROUND: The impact of Pneumocystis jirovecii (formerly P. carinii) dihydropteroate synthase (DHPS) gene mutations on morbidity and mortality of Pneumocystis pneumonia (PCP) in HIV-positive patients is unclear. OBJECTIVE: To determine whether severity and outcome of HIV-associated PCP differs according to DHPS genotype. SETTING: A prospective, observational study in a university-affiliated county hospital. PATIENTS: The study included 197 patients with 215 microscopically confirmed PCP episodes and successfully sequenced DHPS genotypes; 175 (81%) episodes displayed mutant genotypes. MAIN OUTCOME MEASURE: All-cause mortality within 60 days. RESULTS: The majority of patients (86%) with PCP containing Pneumocystis DHPS mutations survived. Although severity of PCP was comparable, there was a trend for more patients with mutant genotypes than patients with wild-type to require mechanical ventilation (14.3% versus 2.5%; P = 0.056) and to die (14.3% versus 7.5%, P = 0.31). Independent predictors of mortality at baseline were low serum albumin levels [odds ratio (OR), 4.62; 95% confidence interval (CI), 1.63-13.1; P = 0.004] and requiring intensive care within 72 h of hospitalization (OR, 5.06; 95% CI, 1.43-18.0; P = 0.012). CONCLUSION: The majority of HIV-infected patients with PCP containing mutant Pneumocystis DHPS genotypes survived. Mortality was related primarily to the underlying severity of illness. However, a trend towards increased mortality in episodes of PCP containing mutant DHPS genotypes was observed and this warrants further study.

Prevalence and clinical predictors of Pneumocystis colonization among HIV-infected men.

BACKGROUND: The epidemiology and transmission of Pneumocystis are poorly understood. The incidence of colonization, or detection of organisms without signs of disease, has been debated, and risk factors for colonization are largely unknown. OBJECTIVE: To determine the rate of Pneumocystis colonization among HIV-infected patients at autopsy and analyze associated clinical variables. METHODS: Subjects were selected from the Multicenter AIDS Cohort Study. Subjects who died from causes other than Pneumocystis pneumonia and consented to autopsy were included in analysis. DNA was extracted from lung tissue, and nested PCR was performed to detect the presence of Pneumocystis. Clinical data were obtained from the Multicenter AIDS Cohort database. Univariate and multivariate analyses were performed to determine predictors of Pneumocystis colonization. RESULTS: Pneumocystis DNA was detected in 42 of 91 (46%) subjects by nested PCR. Clinical variables such as CD4 cell count, use of Pneumocystis prophylaxis or antiretroviral drugs, and history of previous Pneumocystis pneumonia were not related to risk of colonization. Multivariate analysis demonstrated that cigarette smoking was related to an increased risk of colonization [odds ratio (OR), 4.5; 95% confidence interval (CI), 1.27-15.6; P = 0.02] and risk also varied by city of residence (OR, 0.12; 95% CI, 0.03-0.45; P = 0.002 for living in Los Angeles). CONCLUSIONS: This study found a high rate of Pneumocystis colonization among HIV-infected patients. We also identified cigarette smoking and city of residence as novel, independent risk factors for colonization. The role of subclinical colonization in disease transmission and the effects of Pneumocystis colonization on the lung require further study.

Analysis of variation in tandem repeats in the intron of the major surface glycoprotein expression site of the human form of Pneumocystis carinii.

Variation in the tandem repeats in the expression site of the human-derived Pneumocystis carinii major surface glycoprotein gene was characterized by denaturing gel electrophoresis. The number of repeats in 147 isolates ranged from 2 to 6, with 2, 3, and 4 repeats being the most common. Sequence analysis identified 3 types of repeat units that differed by 1 nucleotide, which suggests a hierarchy of evolution of human-derived P. carinii. Examination of sequential samples obtained from 6 patients at an interval of 10-90 days showed an identical repeat pattern in each patient. However, in 2 of 4 patients with 2-3 different samples obtained within 4 days, different repeat patterns were observed among the samples. Quantifying the number of repeats by denaturing gel electrophoresis is a simple and rapid-typing method that can be used alone or in combination with other methods to study the epidemiology of P. carinii.