Outbreak of Pneumocystis Pneumonia in Renal and Liver Transplant Patients Caused by Genotypically Distinct Strains of Pneumocystis jirovecii

Abstract

Background An outbreak of 29 cases of Pneumocystis jirovecii pneumonia (PCP) occurred among renal and liver transplant recipients (RTR and LTR) in the largest Danish transplantation centre between 2007 and 2010, when routine PCP prophylaxis was not used. Methods P. jirovecii isolates from 22 transplant-cases, 2 colonized RTRs and 19 Pneumocystis-control samples were genotyped by restriction fragment length polymorphism and multi-locus sequence typing analysis. Contact tracing were used to investigate transmission. Potential risk factors were compared between PCP cases and matched non-PCP transplant patients. Results Three unique Pneumocystis genotypes were shared among 19 of the RTRs, LTRs and a colonized RTR in 3 distinct clusters, two of which overlapped temporally. In contrast, Pneumocystis-control samples harbored a wide range of genotypes. Evidence of possible nosocomial transmission was observed. Among several potential risk factors, only CMV viremia was consistently associated with PCP (P = 0.03; P = 0.009). Mycophenolate mofetile was associated with PCP risk only in the RTR population (P = 0.04). Conclusion We identified three large groups infected with unique strains of Pneumocystis and provide evidence of an outbreak profile and nosocomial transmission. LTRs may be infected in PCP outbreaks simultaneously with RTRs and by the same strains, most likely by inter-human transmission. Patients are at risk several years after transplantation, but the risk is highest during the first 6 months post-transplantation. Since patients at risk cannot be identified clinically and outbreaks cannot be predicted, six months of PCP chemoprophylaxis should be considered for all renal and liver transplant recipients.

Epidemiological Outbreaks of Pneumocystis jirovecii Pneumonia Are Not Limited to Kidney Transplant Recipients: Genotyping Confirms Common Source of Transmission in a Liver Transplantation Unit

“…This conclusion seems robust because, as shown by the phylogenetic tree, data for the three loci combined were sufficient to discriminate between 24 unrelated P. jirovecii isolates (10). To our knowledge, this is the first genotypic demonstration of clustered PCP limited only to liver transplant patients (24), whereas numerous studies have reported similar findings for kidney recipients (6,10,18), especially in France (10). Thus, in accordance with recent works regarding SOT (26), our study suggests that the use of prophylaxis as widely practiced in most centers of kidney transplantation (22,26) should also be considered thoroughly for liver recipients.…”

“…It should be noted that our institution did not apply systemic anti-PCP chemoprophylaxis for liver transplant patients because the incidence of this opportunistic infection had always remained lower than 0.01 (two cases among 285 patients over 4 years). Indeed, although it has been shown that the risk of acquiring PCP may increase in SOT recipients not taking effective prophylaxis (6,23,24), routine prophylaxis is recommended only for centers with an incidence of PCP of at least 3 to 5% among transplant recipients (25). In such health care settings, trimethoprim-sulfamethoxazole remains the drug of choice (80 to 160/400 to 800 mg orally daily or three times weekly [grade I] for at least 6 to 12 months posttransplantation [grade III]) (26).…”

Anti-CD20 Antibody Therapy and Susceptibility to Pneumocystis Pneumonia

“…These data suggest that anti-CD20 inhibits T-cell priming against P. murina. (22). It is still not known why CD20 ϩ B cells specifically are required to prime CD4 ϩ cell responses to Pneumocystis.…”

“…have a dynamic extracellular proteome as a result of varying their major surface glycoproteins, which may be used to evade the host immune response (26,27). Reports of large genetic variability between Pneumocystis jirovecii isolates also suggest the possibility that patients are simply being exposed to new strains of Pneumocystis (22,28).…”

Genotyping of Pneumocystis jirovecii isolates from human immunodeficiency virus-negative patients in China

“…Molecular typing methods, such as restriction fragment length polymorphism (RFLP) analysis, multiple locus sequence typing, direct DNA sequencing, and variable number of tandem repeats (VNTRs), have been used to analyze the epidemiology of P. jirovecii. A number of independent genomic regions, including the mitochondrial large subunit rRNA (mtLSU rRNA), the rRNA internal transcribed spacer (ITS), the intron of the nuclear 26S rRNA (26S), thymidylate synthase (TS), the variable region of the mitochondrial 26S rRNA gene (mt26S), dihydropteroate synthase (DHPS), dihydrofolate reductase (DHFR), the region surrounding intron number 6 of the btubulin gene (b-tub), superoxide dismutase (SOD), cytochrome b (CYB), thioredoxin reductase (Trr1), 5-enolpyruvylshikimate-3-phosphate synthase (AROM), kexin-like serine protease (Kex1), and upstream conserved sequence (UCS) of the major surface glycoprotein (MSG) gene, have been used to analyze the genetic diversity of P. jirovecii (Esteves et al, 2009(Esteves et al, , 2010Gupta et al, 2013;Rabodonirina et al, 2013;Rostved et al, 2013;Wakefield, 1998). However, among these regions, the ITS, because of its high degree of genetic variation, might be the most discriminatory region for differentiating P. jirovecii isolates (Gupta et al, 2010;Le Gal et al, 2012).…”