Workshops on Opportunistic Protists

Twenty years have passed since the first startling cases of Pnewnocystis carinii pneumonia were reported in gay men. During the intervening time, an explosion of knowledge occurred that focused on clinical diagnosis, therapy, and prophylaxis is HIV-infected individuals and in other immunosuppressed individuals. Concurrently, major advances were made in understanding the cellular and molecular biology of the organism, and in understanding the lung's responses to it. To focus on the current state of knowledge in this field, and to present new experimental data, the International Workshops on Opportunistic Protists were initiated in Bristol, England in 1988 111. These workshops have been reconvened every few years since that h e , and this summary focuses on the 7& International Workshop on Opportunistic Protists, held from June 14-16,2001 in Cincinnati, Ohio. In the last 10 years, much of the conventional scientific and clinical howledge about Pneumocystis has been challenged (Table 1). Using molecular approaches, Pneumocystis was reclassified from protozoan to fungus. While in the pre-1990 era, infections with P. carinii were very common in HIV-infected individuals, these infections are now less common in developed nations, as a result of the use of highly active antiretroviral therapy directed against HIV. However, these potent antiretroviral therapies remain unavailable to millions of HIV-infected individuals in the developing world. Previously, most clinical infections with P. carinii were thought to represent reactivation of latent infections. With molecular biologic approaches, it has now become clear that most cases represent a new acquisition, although the source remains uncertain. Environmental reservoirs seem unlikely, and the bulk of recent evidence implicates person-to-person transmission. Reviously, diagnosis depended on morphologic identification of the organism in respiratory specimens, but detection of DNA by modem methods is supplanting this approach. Therapy and prophylaxis have also undergone striking changes in the last 10 years. Sulfa remains the therapy of choice for infections, despite the high incidence of side effects in HIV-infected individuals. However, the use of adjunctive corticosteroids for patients with moderate to severe disease has decreased morbidity and mortality, probably by blocking the host's inflammatory responses directed against the organism. While aerosolized pentamidine had been a mainstay of prophylaxis, unacceptable rates of failure led to a return to sulfa use. More recently, modem antiretroviral therapy has led to recommendations to discontinue primary and secondary prophylaxis in those individuals who respond to the antiretrovirals with significant immunologic reconstitution. While the prognosis for HIV-infected individuals with respiratory failure has improved, partially because of corticosteroids, the prognosis for other immunosuppressed individuals remains poor. Finally, 10 years ago questions about drug susceptibility and treatment failure were unanswerable. More recently, studies of mutations in the Pnewnocystis genes that serve as drug targets, have produced provocative new information. While it is becoming clear that long-term exposure to sulfa results in increased frequencies of mutant organisms, conclusive proof that these mutations change clinical outcomes remains elusive. All of these aspects were areas of active discussion and debate at the workshop. In the previous Workshop held in 1999, about 70 abstracts were presented dealing with basic and clinical aspects of the Pnewnocystis