|Year : 2014 | Volume
| Issue : 3 | Page : 333-336
Outbreak of Pneumocystis jirovecii pneumonia in renal transplant recipients on prophylaxis: Our observation and experience
P Chandola1, M Lall1, S Sen1, R Bharadwaj2
1 Department of Microbiology, Army Hospital Research and Referral, New Delhi, India
2 Department of Pathology and Molecular Medicine, Army Hospital Research and Referral, New Delhi, India
|Date of Submission||27-Jul-2013|
|Date of Acceptance||17-Oct-2013|
|Date of Web Publication||10-Jul-2014|
Department of Microbiology, Army Hospital Research and Referral, New Delhi
Source of Support: None, Conflict of Interest: None
Pneumocystis jirovecii is a life-threatening opportunistic pathogen affecting immunocompromised hosts, especially renal transplant recipients. This study reports an outbreak of seven such cases, both inpatients and outpatients, occurring in our hospital over a period of 4 months (January-April 2013). All patients were male with a median age of 38 years (range, 28-58 years); the median period between transplantation and diagnosis was 39.5 months (range, 11-123 months). One patient succumbed to the infection. Two were breakthrough cases, developing the infection while on prophylaxis, highlighting the need to view prophylaxis in light of the immunosuppression and clinical picture of such patients.
Keywords: Pneumocystis jirovecii, prophylaxis, renal transplant recipients
|How to cite this article:|
Chandola P, Lall M, Sen S, Bharadwaj R. Outbreak of Pneumocystis jirovecii pneumonia in renal transplant recipients on prophylaxis: Our observation and experience. Indian J Med Microbiol 2014;32:333-6
|How to cite this URL:|
Chandola P, Lall M, Sen S, Bharadwaj R. Outbreak of Pneumocystis jirovecii pneumonia in renal transplant recipients on prophylaxis: Our observation and experience. Indian J Med Microbiol [serial online] 2014 [cited 2020 Aug 9];32:333-6. Available from: http://www.ijmm.org/text.asp?2014/32/3/333/136594
| ~ Introduction|| |
Pneumocystis jirovecii formerly known as Pneumocystis carinii f. sp. hominis is a common opportunistic fungal pathogen causing severe pneumonia known as Pneumocystis jirovecii pneumonia (PJP) in immunocompromised patients. PJP is not only the most commonly occurring acquired immunodeficiency syndrome (AIDS)-defining illness in human immunodeficiency virus (HIV)-infected patients in developed countries, but is also becoming increasingly frequent in non-HIV-infected patients who receive immunosuppressive therapy particularly for organ transplantation.  This unicellular fungus, found ubiquitously in the environment is a feared opportunistic pathogen in the renal transplant population, with a mortality of 90-100% in untreated cases.  The earlier school of thought advocating PJP as occurring from reactivation of latent forms of P. jirovecii present in the lungs has now been replaced. Presently, PJP is considered to result from de novo acquisition of the fungus. 
In renal transplant recipients (RTRs) on heavy immunosuppression, an occurrence of 2-24% of PJP has been seen in patients who did not receive any prophylaxis. The mortality rate in this group of patients has been as high as 49%.  Such data reveals the enormity of PJP as a major public health issue and highlights the importance of preventive prophylaxis in immunocompromised individuals. Most transplant centres now routinely prescribe PJP prophylaxis such as oral trimethoprim-sulfamethoxazole (TMP-SMX), dapsone, atovaquone, pyrimethamine and aerosolised pentamidine. Current European Best Practice Guidelines,  The European Renal Association and the American Society of Transplantation , recommend at least 4 months of PJP prophylaxis post-renal transplantation. Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend 3-6 months.  In the event of acute rejection, an additional prophylaxis during and following the treatment of acute rejection , is also advocated. The actual prophylaxis regime followed is subject to wide variation as per local approach to the disease.
Pneumocystis jirovecii poses various epidemiological complexities. PJP is considered as an anthroponosis, owing to the host specificity of the organisms infecting various mammalian species and the inability to find a plausible animal reservoir for the fungus. Hence, infected cases represent the potential sources of human infection.
The spectrum of clinical manifestations of the infection is diverse and ranges from mild infection or harmless colonisation in most cases to less common but severe, life-threatening pneumonia, especially in the immunocompromised.
Furthermore, despite numerous studies, a clear definition of individual risk factors for the occurrence of PJP in RTRs still eludes the researcher. The risk is regarded to be increased by the overall load of immunosuppression. Not many studies have put forth data regarding the PJP risk of specific immunosuppressants. Age of the donor and co-morbidities of the recipient are other poorly understood factors affecting the patient's risk of developing PJP.
The World Health Organisation defines a disease outbreak as the occurrence of cases of disease in excess of what would normally be expected in a defined community, geographical area or season.
By this definition, we herein report an outbreak of Pneumocystis infection in RTRs, which occurred at our hospital from January through April 2013.
| ~ Case Report|| |
Our renal transplant unit comprises a 20-bedded renal transplant ward, with 3 isolated beds functioning as a renal transplant intensive care unit (ICU) for immediate post-transplant patients and the remaining distributed among three rooms. The renal transplant outpatient department (OPD) is situated about 100 m away on the same floor. This caters to an average of about 500 RTRs on follow-up. There is no common area except for a specialised blood collection counter only for such patients where inpatients and those attending the OPD may come in contact.
The PJP diagnosis was established by microscopic examination of sputum samples received in the laboratory and stained with Gomorri methanamine silver (Grocott) stain [Figure 1]. This was a retrospective study over a period of 4 months, from January to April 2013. On positive PJP microscopy, the case details of the patient were followed up and tabulated as shown in [Table 1].
|Figure 1: Cluster of Pneumocystis jirovecii cysts on Grocott stain Technique - Grocott stain Magnification if any - 100× Salient features - Differential staining of cell wall of cysts (arrows), giving 'cup-in-saucer' appearance|
Click here to view
| ~ Results|| |
Seven RTRs were detected to be harbouring PJP. All were male, with a median age of 38 years (range, 28-58 years); the median post-transplantation period was 39.5 months (range, 11-123 months). Two out of the six patients were on PJP prophylaxis in the form of oral Cotrimoxazole, while the rest were started on treatment once the diagnosis of PJP was confirmed microbiologically.
Our study revealed some interesting facts. First, all seven cases occurred in a short time-span of 4 months, against an earlier incidence of only three cases in 2012 in this hospital, thus qualifying as an outbreak. The first case presented in January 2013 with complaints of fever and cough. However, four of the remaining six were admitted for varied complaints not necessarily respiratory in nature such as dysuria, histoplasmosis, military tuberculosis (TB) and graft rejection. These constituted nosocomially acquired PJP (57%).
Second, all the patients in the study developed PJP more than one year after the transplant, with one patient contracting the infection 11 years later. This lies in contrast with the usual incidence of PJP being highest in the immediate post-transplantation period, which forms the basis of various guidelines on PJP prophylaxis in transplant recipients. ,
Finally, two out of the six RTRs were breakthrough cases, developing PJP in spite of being on oral sulphonamide prophylaxis.
| ~ Discussion|| |
Defects in T-cell immunity predispose to numerous infections, including PJP, the risk being greatest in patients with HIV and transplant recipients, namely lung transplantation and stem cell transplant. The current guidelines for prophylactic therapy in RTRs have largely been extrapolated from data from these groups.  The occurrence of PJP in RTRs was first documented by Lufft et al.  Earlier considered a harmless commensal causing opportunistic infection in setting of immunocompromise, nosocomial outbreaks with colonised patients as reservoirs and human-to-human transmission have been demonstrated by genotype sequencing and other DNA-based studies. , An incidence of 6% is cited in RTRs not receiving any prophylaxis. 
Various risk factors have been implicated in acquisition of PJP. These include number and type of acute rejections, co-infection with cytomegalovirus and other immunomodulating co-infections like TB and hepatitis C. Immunosuppressive regimes play a pivotal role as does PJP prophylaxis.  Presently, a minimum of 3 months (average 3-6 months) PJP prophylaxis is recommended in the early post-transplant period when the immunosuppressive load and consequently, the risk of PJP is highest. Another school of thought recommends that the duration of prophylaxis in susceptible individuals should not be limited to 6 months, but continued until such a time that the immunosuppressive burden can be reduced.  However, breakthrough cases on prophylaxis have been reported with increasing incidence, especially with heavy immunosuppression. ,
Majority of patients in our study presumably contracted the infection during hospital stay, while the index case and two others were admitted with pertinent respiratory complaints. The outbreak was controlled with cotrimoxazole administration to all in-patients. Co-habitation thus emerges as an important contributory factor, supporting the hypothesis of a nosocomial acquisition. Moreover, contact with out-patients, as has been already stated, was minimal. Also, the median time from post-transplantation to infection in our patients varied widely from 11 to 123 months, further pointing towards a possible nosocomial outbreak. Mortality was 14% (one out of seven cases) against about 50% as cited by other studies. , This can be attributed to a high index of suspicion in face of varied clinical presentations, early diagnosis and timely treatment.
| ~ Conclusion|| |
The clustering of PJP cases in a renal transplant centre should always serve as an alert towards a possible nosocomial transmission, irrespective of the actual clinical presentation. A high index of suspicion supported by timely microbiological diagnosis and early treatment undoubtedly improves the mortality. Such outbreaks can be halted by cotrimoxazole administration to all co-habitants, as shown in our study. More importantly, simple but effective measures of controlling spread of the infection among the affected patient population such as hand hygiene in the hospital, wearing of face masks by the patients and preferably, separate rooms for patients symptomatic with respiratory complaints would be prudent components of the overall management.
| ~ References|| |
|1.||Gordon SM, LaRosa SP, Kalmadi S, Arroliga AC, Avery RK, Truesdell-LaRosa L, et al. Should prophylaxis for Pneumocystis carinii pneumonia in solid organ transplant recipients ever be discontinued? Clin Infect Dis 1999;28:240-6. |
|2.||Hughes WT, Feldman S, Sanyal SK. Treatment of Pneumocystis carinii pneumonitis with trimethoprim-sulfamethoxazole. Can Med Assoc J 1975;112:47-50. |
|3.||Keely SP, Stringer JR. Sequences of Pneumocystis carinii f. sp. hominis strains associated with recurrent pneumonia vary at multiple loci. J Clin Microbiol 1997;35:2745-7. |
|4.||EBPG Expert Group on Renal Transplantation. European best practice guidelines for renal transplantation. Section IV: Long-term management of the transplant recipient. IV.7.1 Late infections. Pneumocystis carinii pneumonia. Nephrol Dial Transplant 2002;17:36-9. |
|5.||Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group. KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant 2009;9:S1-155. |
|6.||Di Cocco P, Orlando G, Bonanni L, D'Angelo M, Clemente K, Greco S, et al. A systematic review of two different trimethoprim-sulfamethoxazole regimens used to prevent Pneumocystis jirovecii and no prophylaxis at all in transplant recipients: Appraising the evidence. Transplant Proc 2009;41:1201-3. |
|7.||Lufft V, Kliem V, Behrend M, Pichlmayr R, Koch KM, Brunkhorst R, et al. Incidence of Pneumocystis carinii pneumonia after renal transplantation. Impact of immunosuppression. Transplantation 1996;62:421-3. |
|8.||Le Gal S, Damiani C, Rouillé A, Grall A, Tréguer L, Virmaux M, et al. A cluster of Pneumocystis infections among renal transplant recipients: Molecular evidence of colonized patients as potential infectious sources of Pneumocystis jirovecii. Clin Infect Dis 2012;54:e62-71. |
|9.||Fritzsche C, Riebold D, Fuehrer A, Mitzner A, Klammt S, Mueller-Hilke B, et al. Pneumocystis jirovecii colonization among renal transplant recipients. Nephrology (Carlton) 2013;18:382-7. |
|10.||Gerrard JG. Pneumocystis carinii pneumonia in HIV-negative immunocompromised adults. Med J Aust 1995;162:233-5. |
|11.||Radisic M, Lattes R, Chapman JF, del Carmen Rial M, Guardia O, Seu F, et al. Risk factors for Pneumocystis carinii pneumonia in kidney transplant recipients: A case-control study. Transpl Infect Dis 2003;5:84-93. |
|12.||Fox BC, Sollinger HW, Belzer FO, Maki DG, Maki DG. A prospective, randomized, double-blind study of trimethoprim-sulfamethoxazole for prophylaxis of infection in renal transplantation: Clinical efficacy, absorption of trimethoprim-sulfamethoxazole, effects on the microflora, and the cost-benefit of prophylaxis. Am J Med 1990;89:255-74. |
|13.||Maini R, Henderson KL, Sheridan EA, Lamagni T, Nichols G, Delpech V, et al. Increasing Pneumocystis pneumonia, England, UK, 2000-2010. Emerg Infect Dis 2013;19:386-92. |
|14.||Date A, Krishnaswami H, John GT, Mathai E, Jacob CK, Shastry JC. The emergence of Pneumocystis carinii pneumonia in renal transplant patients in a south Indian hospital. Trans R Soc Trop Med Hyg 1995;89:285. |
|15.||Arend SM, Westendorp RG, Kroon FP, van't Wout JW, Vandenbroucke JP, van Es LA, et al. Rejection treatment and cytomegalovirus infection as risk factors for Pneumocystis carinii pneumonia in renal transplant recipients. Clin Infect Dis 1996;22:920-5. |
|16.||Ellinder CG, Andersson J, Bolinder G, Tyden G. Effectiveness of low-dose cotrimoxazole prophylaxis against Pneumocystis carinii pneumonia after renal and/or pancreas transplantation. Transplant Int 1992;5:81-4. |
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