Molecular Demonstration of a Pneumocystis Outbreak in Stem Cell Transplant Patients: Evidence for Transmission in the Daycare Center

Abstract

Pneumocystis jirovecii pneumonia (PCP) is a life-threatening infection in hematology. Although occasionally reported, the role of interhuman transmission of P. jirovecii in PCP, compared to that of reactivation, remains an unresolved question; the recommendation to isolate PCP patients in the hematology ward are not well evidence-based. Following an unexpected increase in the number of febrile pneumonia patients with P. jirovecii DNA detected in respiratory samples in our hematology ward, we explored 12 consecutive patients from November 2015 to May 2016. Genotyping of P jirovecii was performed using microsatellite markers. The frequency of simultaneous occupancy of these 12 patients in the same unit on the same day from 4 months prior to the first diagnosis was recorded. In three patients, the P. jirovecii genotype could not be determined because DNA was insufficient. One rare single genotype (Gt2) was found in four of the other nine, all allogeneic stem cell transplant recipients. The transmission map showed that these 4 patients had multiple opportunities to meet on the same day (median, 6.5; range, 4–10) at the daycare center. It was much less among the eight non-Gt2 patients (median, 1; range, 0–9; P = 0.048). This study, based on modern molecular technics, strongly suggests that interhuman transmission of P. jirovecii between allogeneic stem cell transplant recipients is possible. P. jirovecii DNA detected in respiratory specimens supports that isolation and respiratory precautions be recommended in such cases in the hematology ward.

Genotyping Pneumocystis jirovecii: Impacting Our Understanding of Interhuman Transmission

“…Outbreaks or clustered cases of PCPs have been reported in different settings, including kidney transplant units, liver transplant units, pediatric oncology wards, hematology wards, and wards of other medical specialties [66,[96][97][98][99]. These outbreaks confirmed the currently accepted hypothesis of airborne transmission between humans, with the ascus (previously called the cyst) as the most probable infecting agent [100,101].…”

“…Immunocompromised patients without full-blown PCP can also serve as a transmitter. The recent study of Robin et al In stem cell transplant patients using STRs evidenced transmission in daycare centers between patients without clinical signs of PCP that harbored low fungal loads in their respiratory samples [98]. This underlies the need of prophylaxis in different clinical situations of immunosuppression using co-trimoxazole [9,108].…”

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“…One of the more frequent mtDNA deletions is the "common deletion" of 4977 base pairs, almost a third of the whole mtDNA genome. This deletion was shown to have a high prevalence in unfertilized oocytes and oocytes from older patients [98,99] as well as in aged cows [100]. Interestingly, work in invertebrates had shown maternal germ cells and oocytes to harbour a much higher rate of mtDNA deletions in comparison to somatic cells [101].…”

Healthcare related transmission of Pneumocystis pneumonia: From key insights toward comprehensive prevention

“…Despite accumulating knowledge of P. jirovecii and PCP, comprehensive infection control recommendations for handling inpatient or outpatient immunocompromised children or adults with proven or suspected PCP have not been issued. Articles reporting outbreaks or clusters of PCP continue to appear in the medical literature, affecting diverse immunosuppressed populations and raising the concern about this issue among infection control teams and a wide spectrum of clinical specialists . Even more worrisome is the high mortality still associated with PCP, which is variably reported between 10% and 40% .…”

“…specialists. [21][22][23] Even more worrisome is the high mortality still associated with PCP, which is variably reported between 10% and 40%. 24 The management of a PCP-case with regard to prevention of transmission encompasses multiple considerations and respective actions that will be reviewed here.…”