Diversity of Pneumocystis jirovecii Across Europe: A Multicentre Observational Study

• Published in: EBioMedicine Vol. 22; no. C; pp. 155 - 163
• Main Authors: Alanio, Alexandre, Gits-Muselli, Maud, Guigue, Nicolas, Desnos-Ollivier, Marie, Calderon, Enrique J., Di Cave, David, Dupont, Damien, Hamprecht, Axel, Hauser, Philippe M., Helweg-Larsen, Jannik, Kicia, Marta, Lagrou, Katrien, Lengerova, Martina, Matos, Olga, Melchers, Willem J.G., Morio, Florent, Nevez, Gilles, Totet, Anne, White, Lewis P., Bretagne, Stéphane
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-08-2017; Elsevier
• Subjects: Adult; Aged; DNA, Fungal; DNA, Fungal - genetics; Europe; Female; Genetic Variation; Genotyping; Genotyping Techniques; Genotyping Techniques - methods; Humans; Life Sciences; Male; Microbiology and Parasitology; Microsatellite Repeats; Microsatellites; Middle Aged; Mixed infection; MLS typing; Mycology; Phylogeny; Phylogeography; Pneumocystis carinii; Pneumocystis carinii - classification; Pneumocystis carinii - genetics; Pneumocystis carinii - isolation & purification; Pneumocystis jirovecii; Pneumonia, Pneumocystis; Pneumonia, Pneumocystis - microbiology; Research Paper; Transmission; Europe; Mixed infection; MLS typing; Microsatellites; Genotyping; Europe; Transmission; Pneumocystis jirovecii
• ISSN: 2352-3964; 2352-3964
• DOI: 10.1016/j.ebiom.2017.06.027

Pneumocystis jirovecii is an airborne human-specific ascomycetous fungus responsible for Pneumocystis pneumonia (PCP) in immunocompromised patients, affecting >500,000 patients per year (www.gaffi.org). The understanding of its epidemiology is limited by the lack of standardised culture. Recent genotyping data suggests a limited genetic diversity of P. jirovecii. The objective of the study was to assess the diversity of P. jirovecii across European hospitals and analyse P. jirovecii diversity in respect to clinical data obtained from the patients.
Genotyping was performed using six already validated short tandem repeat (STR) markers on 249 samples (median: 17 per centre interquartile range [11−20]) from PCP patients of 16 European centres.
Mixtures of STR markers (i.e., ≥2 alleles for ≥1 locus) were detected in 67.6% (interquartile range [61.4; 76.5]) of the samples. Mixture was significantly associated with the underlying disease of the patient, with an increased proportion in HIV patients (78.3%) and a decreased proportion in renal transplant recipients (33.3%) (p<0.001). The distribution of the alleles was significantly different (p<0.001) according to the centres in three out of six markers. In analysable samples, 201 combinations were observed corresponding to 137 genotypes: 116 genotypes were country-specific; 12 in two; six in three; and two in four and one in five countries. Nine genotypes were recorded more than once in a given country. Genotype 123 (Gt123) was significantly associated with France (14/15, p<0.001) and Gt16 with Belgium (5/5, p<0.001). More specifically, Gt123 was observed mainly in France (14/15/16 patients) and in renal transplant patient (13/15).
Our study showed the wide population diversity across Europe, with evidence of local clusters of patients harbouring a given genotype. These data suggest a specific association between genotype and underlying disease, with evidence of a different natural history of PCP in HIV patients and renal transplant recipients.
•Limited number of P. jirovecii genetic complexes across Europe but high number of genotypes uncovered.•Association between mixture of genotype and HIV patients.•Specific relationship between renal transplant recipients and specific P. jirovecii genotypes with the description of multiple local transmissions.•Potential geographical and temporal dissemination of a given genotype within an area of 600km.
Pneumocystis jirovecii is an airborne opportunistic fungal organism. As it is not culturable, genotyping and population genetics is difficult. We implemented recently a method allowing us to genotype the largest cohort of P. jirovecii isolates (n=249) across Europe. We evidenced that HIV patients were more prone to harbour mixtures of genotypes compared to other underlying diseases, that local transmission of a given genotype was frequent in renal transplant recipients with potential dissemination within a timescale of several years and an area of 600km. This work advances our understanding of the population structure and the transmission of P. jirovecii in humans.