title: Interhuman transmission as a potential key parameter for geographical variation in the prevalence of Pneumocystis jirovecii dihydropteroate synthase mutations.
abstract: BACKGROUND
  Pneumocystis jirovecii dihydropteroate synthase (DHPS) mutations are associated with failure of prophylaxis with sulfa drugs. This retrospective study sought to better understand the geographical variation in the prevalence of these mutations.
  
  
  METHODS
  DHPS polymorphisms in 394 clinical specimens from immunosuppressed patients who received a diagnosis of P. jirovecii pneumonia and who were hospitalized in 3 European cities were examined using polymerase chain reaction (PCR) single-strand conformation polymorphism. Demographic and clinical characteristics were obtained from patients' medical charts.
  
  
  RESULTS
  Of the 394 patients, 79 (20%) were infected with a P. jirovecii strain harboring one or both of the previously reported DHPS mutations. The prevalence of DHPS mutations was significantly higher in Lyon than in Switzerland (33.0% vs 7.5%; P < .001). The proportion of patients with no evidence of sulfa exposure who harbored a mutant P. jirovecii DHPS genotype was significantly higher in Lyon than in Switzerland (29.7% vs 3.0%; P < .001). During the study period in Lyon, in contrast to the Swiss hospitals, measures to prevent dissemination of P. jirovecii from patients with P. jirovecii pneumonia were generally not implemented, and most patients received suboptimal prophylaxis, the failure of which was strictly associated with mutated P. jirovecii. Thus, nosocomial interhuman transmission of mutated strains directly or indirectly from other individuals in whom selection of mutants occurred may explain the high proportion of mutations without sulfa exposure in Lyon.
  
  
  CONCLUSIONS
  Interhuman transmission of P. jirovecii, rather than selection pressure by sulfa prophylaxis, may play a predominant role in the geographical variation in the prevalence in the P. jirovecii DHPS mutations.
authors.affiliation: Institute of Microbiology, Swiss HIV Cohort Study, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
authors.forename: Philippe M
authors.initials: PM
authors.lastname: Hauser
authors.forename: Aimable
authors.initials: A
authors.lastname: Nahimana
authors.forename: Patrick
authors.initials: P
authors.lastname: Taffe
authors.forename: Rainer
authors.initials: R
authors.lastname: Weber
authors.forename: Patrick
authors.initials: P
authors.lastname: Francioli
authors.forename: Jacques
authors.initials: J
authors.lastname: Bille
authors.forename: Meja
authors.initials: M
authors.lastname: Rabodonirina
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000935:Antifungal Agents / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004271:DNA, Fungal / Q000235:genetics; D004094:Dihydropteroate Synthase / Q000235:genetics*; D025141:Drug Resistance, Fungal; D005060:Europe; D005260:Female; D005656:Fungal Proteins / Q000235:genetics*; D005787:Gene Frequency; D005843:Geography; D006801:Humans; D008297:Male; D008875:Middle Aged; D045363:Pneumocystis carinii / Q000201:enzymology* / Q000235:genetics / Q000302:isolation & purification; D011020:Pneumonia, Pneumocystis / Q000382:microbiology* / Q000635:transmission*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012641:Selection, Genetic; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D004271:DNA, Fungal; D005656:Fungal Proteins; D004094:Dihydropteroate Synthase