Marwan M Azar1, Elizabeth Cohen2, Liang Ma3, Ousmane H Cissé3, Geliang Gan4, Yanhong Deng4, Kristen Belfield5, William Asch2,5, Matthew Grant1, Shana Gleeson1, Alan Koff6, David C Gaston7, Jeffrey Topal1, Shelly Curran3, Sanjay Kulkarni2,8, Joseph A Kovacs3, Maricar Malinis1,8. 1. Department of Internal Medicine, Section of Infectious Diseases, Yale School of Medicine, New Haven, Connecticut,USA. 2. Kidney Transplantation Program, Yale-New Haven Hospital, New Haven, Connecticut, USA. 3. Critical Care Medicine Department, NIH Clinical Center, Bethesda, Maryland, USA. 4. Yale Center for Analytical Sciences, Yale School of Public Health, New Haven, Connecticut, USA. 5. Department of Internal Medicine, Section of Nephrology, Yale School of Medicine, New Haven, Connecticut, USA. 6. Department of Internal Medicine, Section of Infectious Diseases, UC Davis School of Medicine, Sacramento, California, USA. 7. Department of Pathology, Division of Medical Microbiology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA. 8. Department of Surgery, Yale School of Medicine, New Haven, Connecticut, USA.
Abstract
BACKGROUND: Pneumocystis jirovecii is an opportunistic fungus that causes Pneumocystis pneumonia (PCP) in immunocompromised hosts. Over an 11-month period, we observed a rise in cases of PCP among kidney-transplant recipients (KTR), prompting an outbreak investigation. METHODS: Clinical and epidemiologic data were collected for KTR diagnosed with PCP between July 2019 and May 2020. Pneumocystis strain typing was performed using restriction fragment length polymorphism analyses and multilocus sequence typing in combination with next-generation sequencing. A transmission map was drawn, and a case-control analysis was performed to determine risk factors associated with PCP. RESULTS: Nineteen cases of PCP in KTR were diagnosed at a median of 79 months post-transplantation; 8 received monthly belatacept infusions. Baseline characteristics were similar for KTR on belatacept versus other regimens; the number of clinic visits was numerically higher for the belatacept group during the study period (median 7.5 vs 3). Molecular typing of respiratory specimens from 9 patients revealed coinfection with up to 7 P. jirovecii strains per patient. A transmission map suggested multiple clusters of interhuman transmission. In a case-control univariate analysis, belatacept, lower absolute lymphocyte count, non-White race, and more transplant clinic visits were associated with an increased risk of PCP. In multivariate and prediction power estimate analyses, frequent clinic visits was the strongest risk factor for PCP. CONCLUSIONS: Increased clinic exposure appeared to facilitate multiple clusters of nosocomial PCP transmission among KTR. Belatacept was a risk factor for PCP, possibly by increasing clinic exposure through the need for frequent visits for monthly infusions.
BACKGROUND: Pneumocystis jirovecii is an opportunistic fungus that causes Pneumocystis pneumonia (PCP) in immunocompromised hosts. Over an 11-month period, we observed a rise in cases of PCP among kidney-transplant recipients (KTR), prompting an outbreak investigation. METHODS: Clinical and epidemiologic data were collected for KTR diagnosed with PCP between July 2019 and May 2020. Pneumocystis strain typing was performed using restriction fragment length polymorphism analyses and multilocus sequence typing in combination with next-generation sequencing. A transmission map was drawn, and a case-control analysis was performed to determine risk factors associated with PCP. RESULTS: Nineteen cases of PCP in KTR were diagnosed at a median of 79 months post-transplantation; 8 received monthly belatacept infusions. Baseline characteristics were similar for KTR on belatacept versus other regimens; the number of clinic visits was numerically higher for the belatacept group during the study period (median 7.5 vs 3). Molecular typing of respiratory specimens from 9 patients revealed coinfection with up to 7 P. jirovecii strains per patient. A transmission map suggested multiple clusters of interhuman transmission. In a case-control univariate analysis, belatacept, lower absolute lymphocyte count, non-White race, and more transplant clinic visits were associated with an increased risk of PCP. In multivariate and prediction power estimate analyses, frequent clinic visits was the strongest risk factor for PCP. CONCLUSIONS: Increased clinic exposure appeared to facilitate multiple clusters of nosocomial PCP transmission among KTR. Belatacept was a risk factor for PCP, possibly by increasing clinic exposure through the need for frequent visits for monthly infusions.
Authors: Christina D Mejia; Gregory E Malat; Suzanne M Boyle; Karthik Ranganna; Dong Heun Lee Journal: Transpl Infect Dis Date: 2020-12-02 Impact factor: 2.228
Authors: A Dumoulin; E Mazars; N Seguy; D Gargallo-Viola; S Vargas; J C Cailliez; E M Aliouat; A E Wakefield; E Dei-Cas Journal: Eur J Clin Microbiol Infect Dis Date: 2000-09 Impact factor: 3.267
Authors: Andreas A Rostved; Monica Sassi; Jørgen A L Kurtzhals; Søren Schwartz Sørensen; Allan Rasmussen; Christian Ross; Emile Gogineni; Charles Huber; Geetha Kutty; Joseph A Kovacs; Jannik Helweg-Larsen Journal: Transplantation Date: 2013-11-15 Impact factor: 4.939
Authors: Solène Le Gal; Laurence Pougnet; Céline Damiani; Emilie Fréalle; Paul Guéguen; Michèle Virmaux; Séverine Ansart; Sylvain Jaffuel; Francis Couturaud; Aurélien Delluc; Jean-Marie Tonnelier; Philippe Castellant; Yann Le Meur; Gaétan Le Floch; Anne Totet; Jean Menotti; Gilles Nevez Journal: Diagn Microbiol Infect Dis Date: 2015-01-15 Impact factor: 2.803