Diversity of Pneumocystis jirovecii Across Europe: A Multicentre Observational Study
Alexandre Alanio,
Maud Gits-Muselli,
Nicolas Guigue,
Marie Desnos-Ollivier,
Enrique J. Calderon,
David Di Cave,
Damien Dupont,
Axel Hamprecht,
Philippe M. Hauser,
Jannik Helweg-Larsen,
Marta Kicia,
Katrien Lagrou,
Martina Lengerova,
Olga Matos,
Willem J.G. Melchers,
Florent Morio,
Gilles Nevez,
Anne Totet,
Lewis P. White,
Stéphane Bretagne
Affiliations
Alexandre Alanio
Laboratoire de Parasitologie-Mycologie, AP-HP, Groupe Hospitalier Saint-Louis-Lariboisière-Fernand-Widal, Paris, France
Maud Gits-Muselli
Laboratoire de Parasitologie-Mycologie, AP-HP, Groupe Hospitalier Saint-Louis-Lariboisière-Fernand-Widal, Paris, France
Nicolas Guigue
Laboratoire de Parasitologie-Mycologie, AP-HP, Groupe Hospitalier Saint-Louis-Lariboisière-Fernand-Widal, Paris, France
Marie Desnos-Ollivier
Institut Pasteur, CNRS, Unité de Mycologie Moléculaire, Centre National de Référence Mycoses Invasives et Antifongiques, URA3012, Paris, France
Enrique J. Calderon
CIBER de Epidemiología y Salud Pública, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío, CSIC, Universidad de Sevilla, Spain
David Di Cave
Department of Clinical Sciences and Translational Medicine, University of Rome “Tor Vergata”, Italy
Damien Dupont
Hospices Civils de Lyon, Institut des Agents Infectieux, Parasitologie Mycologie, Hôpital de la Croix-Rousse, Integrative Physiology of the Brain Arousal Systems, Centre de Recherche en Neurosciences de Lyon, INSERM U1028-CNRS UMR 5292, Faculté de Médecine, Université Claude Bernard Lyon 1, Lyon F-69000, France
Axel Hamprecht
Institute for Medical Microbiology, Immunology and Hygiene, University Hospital Cologne, Germany
Philippe M. Hauser
Institute of Microbiology, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland
Jannik Helweg-Larsen
Department of Infectious Diseases, Rigshospitalet-Copenhagen University Hospital, Copenhagen, Denmark
Marta Kicia
Department of Biology & Medical Parasitology, Wroclaw Medical University, Wroclaw, Poland
Katrien Lagrou
Department of Microbiology and Immunology, Catholic University Leuven, Leuven, Belgium and National Reference Centre for Mycosis, Department of Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium
Martina Lengerova
Department of Internal Medicine - Hematology and Oncology, University Hospital Brno, Brno, Czech Republic
Olga Matos
TB, HIV and Opportunistic Diseases and Pathogens, Global Health and Tropical Medicine, Lisboa, Portugal
Willem J.G. Melchers
Department of medical microbiology, Radboud University Medical Centre, Nijmegen, The Netherlands
Florent Morio
Parasitology and Mycology laboratory, Nantes University Hospital, Nantes, France
Gilles Nevez
University of Brest, GEIHP EA 3142, Laboratory of Parasitology and Mycology, Brest University Hospital, Brest, France
Anne Totet
University of Picardy-Jules Verne, EA 4285 UMR-I 01 INERIS, Department of Parasitology and Mycology, Amiens University Hospital, Amiens, France
Lewis P. White
Public Health Wales, Microbiology Cardiff, UHW, Heath Park, Cardiff, UK
Stéphane Bretagne
Laboratoire de Parasitologie-Mycologie, AP-HP, Groupe Hospitalier Saint-Louis-Lariboisière-Fernand-Widal, Paris, France
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.
