Epidemiology and clinical relevanceof<i>Pneumocystis jirovecii</i>Frenkel, 1976 dihydropteroate synthase gene mutations

Matos, Olga; Esteves, Francisco

doi:10.1051/parasite/2010173219

Cited by 33 publications

(21 citation statements)

References 20 publications

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“…These data support the hypothesis on the existence of geographical variations in the prevalence of P. jirovecii DHPS gene mutations because of intrinsic epidemiological factors in each location that influence the circulation and transmission of different genotypes and that also may reflect and contribute to the differences in the use and effects of sulfonamides for PcP prophylaxis and treatment of bacterial diseases (9,35,45,46). However, the effects of mutant strains on clinical illness and outcomes of PcP have not been clearly defined.…”

Section: Discussionsupporting

confidence: 64%

“…The DHPS gene is involved in the essential biosynthesis of folic acid and has been used as a marker for changes in levels of susceptibility to sulfa and sulfone drugs, as well as for P jirovecii characterization (9). Variations in this gene have been associated with previous sulfa drug exposition (9,41). In the present study, 16/48 specimens (33.3%) were genotyped by PCR-RFLP analysis of the DHPS locus.…”

Section: Discussionmentioning

confidence: 99%

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Prevalence and Genotype Distribution of Pneumocystis jirovecii in Cuban Infants and Toddlers with Whooping Cough

et al. 2014

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e This study describes the prevalence and genotype distribution of Pneumocystis jirovecii obtained from nasopharyngeal (NP) swabs from immunocompetent Cuban infants and toddlers with whooping cough (WC). A total of 163 NP swabs from 163 young Cuban children with WC who were admitted to the respiratory care units at two pediatric centers were studied. The prevalence of the organism was determined by a quantitative PCR (qPCR) assay targeting the P. jirovecii mitochondrial large subunit (mtLSU) rRNA gene. Genotypes were identified by direct sequencing of mtLSU ribosomal DNA (rDNA) and restriction fragment length polymorphism (RFLP) analysis of the dihydropteroate synthase (DHPS) gene amplicons. qPCR detected P. jirovecii DNA in 48/163 (29.4%) samples. mtLSU rDNA sequence analysis revealed the presence of three different genotypes in the population. Genotype 2 was most common (48%), followed in prevalence by genotypes 1 (23%) and 3 (19%); mixed-genotype infections were seen in 10% of the cases. RFLP analysis of DHPS PCR products revealed four genotypes, 18% of which were associated with resistance to sulfa drugs. Only contact with coughers (prevalence ratio [PR], 3.51 [95% confidence interval {CI}, 1.79 to 6.87]; P ‫؍‬ 0.000) and exposure to tobacco smoke (PR, 1.82 [95% CI, 1.14 to 2.92]; P ‫؍‬ 0.009) were statistically associated with being colonized by P. jirovecii. The prevalence of P. jirovecii in infants and toddlers with WC and the genotyping results provide evidence that this population represents a potential reservoir and transmission source of P. jirovecii.

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Section: Discussionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Prevalence and Genotype Distribution of Pneumocystis jirovecii in Cuban Infants and Toddlers with Whooping Cough

et al. 2014

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“…These variations may be important molecular shifts influencing the pathogenesis of the organism and the clinical outcome of the PcP cases (5,7,14,15,24,25). Typing P. jirovecii SNPs should meet certain specific selection criteria, which include their frequency, location, and type of change (10,19).…”

Section: Discussionmentioning

confidence: 99%

“…Pneumocystis jirovecii is an opportunistic pathogen capable of causing fatal pneumonia (PcP), which is frequently the first serious illness encountered by human immunodeficiency virus (HIV)-infected persons (1,25,29). One major problem in P. jirovecii research is the absence of an in vitro culture system.…”

mentioning

confidence: 99%

Clinical Relevance of Multiple Single-Nucleotide Polymorphisms in Pneumocystis jirovecii Pneumonia: Development of a Multiplex PCR-Single-Base-Extension Methodology

et al. 2011

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Pneumocystis jirovecii pneumonia (PcP) is a major cause of respiratory illness in patients with AIDS. The identification of multiple single-nucleotide polymorphisms (SNPs) at three distinct P. jirovecii loci encoding dihydrofolate reductase (DHFR), mitochondrial large-subunit rRNA (mtLSU rRNA), and superoxide dismutase (SOD) was achieved using multiplex-PCR (MPCR) followed by direct sequencing and two single-base extension (SBE) techniques. Four SNPs (DHFR312, mt85, SOD215, and SOD110), correlated previously with parameters of disease, were amplified and genotyped simultaneously. The concordance of results between the standard sequencing technique (direct sequencing) and SBE analysis was 96.9% for the acrylamide gel electrophoresis and 98.4% for the capillary electrophoresis. The cross-genetic analysis established several statistical associations among the SNPs studied: mt85C-SOD110T, SOD110T-SOD215C, and SOD110C-SOD215T. These results were confirmed by cluster analysis. Data showed that among the isolates with low to moderate parasite burden, the highest percentages of DHFR312C, mt85C, SOD110T, and SOD215C were detected, whereas for high parasite burden cases the highest frequencies were observed among isolates with DHFR312T, mt85T, SOD110C, and SOD215T. The polymorphisms studied were shown to be suitable genetic targets potentially correlated with PcP clinical data that can be used as predictors of outcome in further studies to help clinical decision-making in the management of PcP. The MPCR/SBE protocol described for the first time in the present study was shown to be a rapid, highly accurate method for genotyping P. jirovecii SNPs encoded by different loci that could be used for epidemiological studies and as an additional procedure for the prognostic classification and diagnosis of PcP.

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“…In the United States and Europe, the prevalence of two of the most common dhps mutations (those at codons 55 and 57) in patients with PCP has been reported between 23-81% (in the USA) and 7-57% (in Europe). [6] Estimates of the independent effect of P. jirovecii mutants upon clinical outcomes have been conflicting: some studies report their association with increased mortality or antifolate-based treatment failure, [7][8][9][10] while others have not [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Low Prevalence Of Pneumocystis Pneumonia (PCP) But High Prevalence Of Pneumocystis Dihydropteroate Synthase (DHPS) Gene Mutations In HIV-Infected Persons In Uganda

Huang

Taylor

Worodria

et al. 2010

C104. Hiv Associated Lung Disease Including Pneumocystis

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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.

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Epidemiology and clinical relevanceofPneumocystis jiroveciiFrenkel, 1976 dihydropteroate synthase gene mutations

Cited by 33 publications

References 20 publications

Prevalence and Genotype Distribution of Pneumocystis jirovecii in Cuban Infants and Toddlers with Whooping Cough

Prevalence and Genotype Distribution of Pneumocystis jirovecii in Cuban Infants and Toddlers with Whooping Cough

Clinical Relevance of Multiple Single-Nucleotide Polymorphisms in Pneumocystis jirovecii Pneumonia: Development of a Multiplex PCR-Single-Base-Extension Methodology

Low Prevalence Of Pneumocystis Pneumonia (PCP) But High Prevalence Of Pneumocystis Dihydropteroate Synthase (DHPS) Gene Mutations In HIV-Infected Persons In Uganda

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