Genotyping of Pneumocystis jiroveci pneumonia in Italian AIDS patients. Clinical outcome is influenced by dihydropteroate synthase and not by internal transcribed spacer genotype
| Autor: | Antonietta Cargnel, Elisa Tronconi, Piergiorgio Duca, Francesca Mazza, Antonella Valerio, Giovanna Fantoni, Chiara Atzori, Federica Tartarone |
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| Rok vydání: | 2007 |
| Předmět: |
Adult
Male Genes Viral DHPS Biology Pneumocystis carinii Polymerase Chain Reaction chemistry.chemical_compound Viral Proteins Species Specificity Lactate dehydrogenase parasitic diseases Genotype Trimethoprim Sulfamethoxazole Drug Combination medicine Humans Pharmacology (medical) Typing Genotyping Aged Dihydropteroate Synthase Polymorphism Genetic AIDS-Related Opportunistic Infections Pneumonia Pneumocystis HIV Middle Aged Virology Trimethoprim Infectious Diseases Treatment Outcome chemistry Italy Mutation Disease Progression DNA Intergenic Female Restriction fragment length polymorphism Dihydropteroate synthase medicine.drug |
| Zdroj: | Journal of acquired immune deficiency syndromes (1999). 45(5) |
| ISSN: | 1525-4135 |
| Popis: | Background Two Pneumocystis jiroveci independent genomic regions, internal transcribed spacer (ITS) 1 and ITS2, and dihydropteroate synthase (DHPS) gene have been used for typing a cohort of HIV-infected Italian patients with P jiroveci pneumonia (PcP). Methods Bronchoalveolar lavage samples isolated from 207 HIV-infected adults were ITS and DHPS genotyped by DNA sequencing and by restriction fragment length polymorphism analysis, respectively. Mutant DHPS samples were cloned and ITS typed. Data on severity, treatment, and outcome of PcP were obtained by chart review. Results High diversity with 46 different ITS genotypes was observed. At the DHPS locus, 9.1% of samples analyzed were found to be mutated. A correlation was observed between DHPS mutants and greater severity of PcP, as defined by higher lactate dehydrogenase (P = 0.015) and need for intubation (P = 0.002), and worse outcomes, as defined by failure of sulfa treatment (P = 0.04), death, and/or relapse of PcP (P = 0.008). There was a significant difference in ITS genotype patterns between DHPS wild-type and mutants (P = 0.028). Conclusions The present data suggest the absence of a correlation between P jiroveci ITS types and specific clinical characteristics. DHPS mutations correlate with possible failure of anti-P jiroveci sulfa therapy, and a trend of association is shown between DHPS mutations and some clinical PcP features. |
| Databáze: | OpenAIRE |
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