Transmission of Pneumocystis species among renal transplant recipients.

Investigation of the transmission and epidemiology of Pneumocystis species in humans is hampered by several confounding variables imposed by both the organism and the host. The disease, a highly fatal pneumonitis, occurs almost exclusively in the severely immunocompromised host, who is also at high risk for other oppor-tunistic infections of the lungs, with and without Pneumocystis jiroveci (also called Pneumocystis carinii) pneumonia (PCP). Furthermore, asymptomatic Pneumocystis infection occurs to the extent of serocon-version with detectable antibody in 175% of healthy individuals by 4 years of age, rendering serologic analysis useless as an epidemiological tool. The organism may reside as a latent form in the lungs for long periods of time. A conclusive diagnosis of PCP for research purposes requires the demonstration of pneumonitis by radiography, plus the identification of Pneumocystis species in pulmonary paren-chyma by examination of bronchoalveolar lavage fluid or biopsy specimens. Microscopic examination of stained specimens is the standard method for identification of the organism. In recent years, the use of molecular techniques, such as PCR with DNA-based methods, have been utilized in epidemiological investigations. In human studies, the method used most often has been nested PCR that uses primers targeting the mitochondrial large subunit r RNA (mtLSU) of Pneumocystis species. A point to be made here—and one often not appreciated in some clinical studies— is that the histologic and molecular methods identify different entities: an infectious agent as a whole intact organism (cyst and trophozoite) with the former method and a molecular fraction of the organism with the latter method. Thus, PCR does not distinguish between intact Pneumocystis species and fragments of disrupted organisms. Chemoprophylaxis for PCP in immu-nocompromised hosts is highly effective. As a standard of medical practice, pro-phylaxis has profoundly reduced the incidence and prevalence of PCP to the extent that an adequate number of subjects (even those with AIDS) is difficult to accrue for statistically sound studies. In addition , circumstances in which some of the subjects receive prophylaxis and some do not may complicate the experimental design. Clearly, the incidence of PCP is directly related to the type and intensity of immunosuppressive therapy that affects cell-mediated immunity. It is noteworthy that the extent of immunosuppression may vary among patients under the same protocol for immunosuppressive treatment , as shown by pharmacogenetic and comparative studies. The study by de Boer et al. [1] illustrates the difficulties investigators face with the aforementioned factors in clinical …