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Published on: February 15, 2013
Diversity of Pneumocystis jirovecii Across Europe: A Multicentre Observational Study
Alexandre Alanio1, Maud Gits-Muselli2, Nicolas Guigue3
1Laboratoire de Parasitologie-Mycologie, AP-HP, Groupe Hospitalier Saint-Louis-Lariboisière-Fernand-Widal, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, Paris, France; Institut Pasteur, CNRS, Unité de Mycologie Moléculaire, Centre National de Référence Mycoses Invasives et Antifongiques, URA3012, Paris, France.
Abstract:
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.
Insights
Pneumocystis jirovecii shows significant genetic diversity across European hospitals, with specific genotypes linked to patient conditions like HIV and kidney transplants, suggesting varied disease progression.
Area of Science:
- Medical Mycology
- Infectious Diseases Epidemiology
- Molecular Diagnostics
Background:
- Pneumocystis jirovecii causes Pneumocystis pneumonia (PCP) in immunocompromised individuals.
- Limited understanding of P. jirovecii epidemiology due to lack of standardized culturing.
- Previous genotyping suggested low genetic diversity.
Purpose of the Study:
- To assess P. jirovecii genetic diversity across European hospitals.
- To analyze the association between P. jirovecii genotypes and patient clinical data.
Main Methods:
- Genotyping of 249 P. jirovecii samples from 16 European centers using six short tandem repeat (STR) markers.
- Analysis of STR marker mixtures and allele distribution.
- Correlation of identified genotypes with patient underlying diseases and geographical origin.
Main Results:
- Mixtures of STR markers were detected in 67.6% of samples, significantly associated with underlying disease (higher in HIV patients, lower in renal transplant recipients).
- Significant differences in allele distribution were observed across centers for three out of six markers.
- 137 distinct P. jirovecii genotypes were identified, with 116 being country-specific. Specific genotypes (Gt123, Gt16) showed significant geographical associations (France, Belgium).
- Genotype 123 was notably associated with renal transplant patients.
Conclusions:
- P. jirovecii exhibits wide population diversity across Europe, with evidence of local genotype clusters.
- A specific association exists between P. jirovecii genotype and the patient's underlying disease.
- Data suggest a different natural history of PCP in HIV patients compared to renal transplant recipients.
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