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Excerpt
Current concepts regarding the fungal pathogen Pneumocystis carinii are reviewed. Despite a substantial decline in incidence, P. carinii pneumonia (PCP) remains the most common life-threatening opportunistic infection diagnosed in HIV-infected patients. Molecular and immunologic studies have demonstrated that there are multiple strains of P. carinii, each restricted to infecting a single host species. In addition target enzymes of some available therapeutic regimens have been cloned, sequenced and characterized, including the genes encoding dihydropteroate synthase (DHPS) and dihydrofolate reductase, targets of sulfamethoxazole and trimethoprim, respectively.
The development of a fluorescent antibody stain utilizing monoclonal antibodies to human P. carinii has proved to be both sensitive and specific, allowing detection of the organism within 2 h. However, the introduction of molecular based methods has provided detection assays that are more sensitive than traditional stains (i.e. Giemsa, Gomori methenamine silver, Gram-Wiegert or toluidine blue O) or immunofluorescent stains. PCR methods with the highest sensitivity use either a multicopy gene target (e.g. mitochondrial ribosomal RNA, major surface glycoprotein) or a nested PCR procedure requiring two amplification rounds.
Although drug resistance in P. carinii cannot be confirmed by the usual methods because culture of patient isolates is not possible, resistance may be determined indirectly by determining mutations in the P. carinii DHPS gene. Specific genetic polymorphisms identified are suggestive of evolutionary selective pressure to induce mutations, possibly as a result of drug exposure. There is widespread geographic variation in the prevalence of these mutations.
Comment: Chemoprophylaxis of PCP represents one of the major successes in the field of infectious diseases in the past 25 years. Adherence to well-established regimens during periods of immunologic susceptibility and appropriate patient education regarding the importance of prophylaxis are essential to PCP prevention. The prophylaxis failure rate related to sulfonamide resistance remains to be determined.
