New Insights Into Transmission, Diagnosis, and Drug Treatment of <EMPH TYPE="ITAL">Pneumocystis carinii</EMPH> Pneumonia

Abstract

Pneumocystis carinii has been recognized as a human pathogen for nearly 50 years. We present a case of P carinii infection that typifies clinical presentation in the era of the acquired immunodeficiency syndrome epidemic. The high incidence of P carinii pneumonia in persons infected with human immunodeficiency virus (HIV) has served to focus laboratory and clinical research efforts on better understanding the biology of the organism and on improving diagnosis, treatment, and prevention of this disease. Although inability to culture P carinii has hampered research efforts, molecular and immunologic approaches have led to the recognition that the organism represents a family of fungi with a very restricted host range and have allowed characterization of clinically relevant antigens and enzymes. Molecular epidemiologic studies have identified more than 50 strains of human-derived P carinii and have suggested that recently acquired infection, as opposed to reactivation of latent infection, may account for many cases of clinical disease. Diagnosis has been improved by the development of organism-specific monoclonal antibodies and, more recently, by polymerase chain reaction using multicopy gene targets, together with induced sputum or oral wash samples. Chemotherapeutic prophylaxis is very effective in preventing P carinii pneumonia; the combination of trimethoprim-sulfamethoxazole remains the first-line agent for both therapy and prophylaxis. Prophylaxis needs to be administered only during periods of high risk; in HIV-infected patients responding to effective antiretroviral therapies, prophylaxis no longer needs to be lifelong. Molecular studies have identified mutations in the target of sulfa drugs that appear to represent emerging resistance in P carinii. Resistance to atovaquone, a second-line agent, may also be developing.

Immunocompromised Group Differences in the Presentation of Intestinal Strongyloidiasis

“…A number of studies have validated these presenting symptoms as being the most common in HIV patients without other coexisting illnesses (9), although Chakravarty et al (10) and Vajpayee et al (11) also classified diarrhea as an opportunistic infection, along with tuberculosis and oral candidiasis. To complicate matters further, HIV patients with Pneumocystis jirovecii pneumonia also present fever and a productive cough (12), a finding that is similar to our results. Patients with strongyloidiasis alone without HIV or opportunistic infections also present fever, abdominal pain and diarrhea (13).…”

A Molecular Window into the Biology and Epidemiology of Pneumocystis spp

“…In agreement with the hypothesis of low pressure on dhfr, in vitro inhibition assays using recombinant enzymes (557) and yeast complementation (558) demonstrated that TMP as well as, to a lesser extent, pyrimethamine is a relatively poor inhibitor of wild-type P. jirovecii Dhfr. These findings support the concept that TMP contributes little to the effectiveness of TMP-SMX against P. jirovecii, which may in fact function as sulfa monotherapy (26,54).…”

Ab initiocalcineurin inhibitor-based monotherapy immunosuppression after liver transplantation reduces the risk forPneumocystis jiroveciipneumonia

“…Our data suggest that IS monotherapy after LT may nullify the risk for PCP even in the absence of any specific prophylaxis. Given that the net state of IS determines the development of PCP (1–4, 11), it is reasonable to ascribe these findings to the minimal impairment of the immune system induced in our patients. At our center, monotherapy IS has been the standard treatment since January 2001 (18) and the concept of minimal IS has been strictly adhered to: target trough levels are low, steroids and induction IS are not administered (14), stable patients are regularly weaned off IS (19–22), and only severe cases of acute rejection are treated with additional IS (15).…”