Development Of Pneumocystis Carinii Pneumonia Research Articles

Development of Pneumocystis carinii pneumonia in patients with immunobullous and connective tissue disease receiving immunosuppressive medications

Pneumocystis carinii pneumonia (PCP) causes morbidity and mortality in immunocompromised hosts. Data describing use of PCP prophylaxis in immunosuppressed dermatologic patients are lacking. We sought to describe the frequency of PCP among dermatologic patients receiving immunosuppression for immunobullous disease or connective tissue disease. We retrospectively reviewed the cases of patients with immunobullous and connective tissue disease at our department of dermatology between 1980 and 2006 who received immunosuppression and had subsequent development of pneumonia. We recorded patient characteristics, use of PCP prophylaxis, whether PCP developed, and if so, their morbidity and mortality. Of 334 patients identified, 7 (2.1%) were given the diagnosis of PCP during immunosuppressive treatment. Of these 7 patients, 3 (43%) died within 1 month of diagnosis, and none received PCP prophylaxis. Retrospective study design and limited patient group are limitations. PCP prophylaxis may improve outcomes for some patients with immunobullous or connective tissue disease receiving immunosuppressive therapy.

Pneumocystis carinii infection in non-AIDS patients

Infection with the opportunist fungus Pneumocystis carinii remains a significant cause of morbidity and mortality in non-HIV-infected individuals immunosuppressed by a wide range of malignancies, transplantation and inflammatory conditions. Glucocorticoid use appears to be an independent risk factor for the development of Pneumocystis carinii pneumonia. Transmission from infected to susceptible patients may occur, albeit infrequently. A diagnosis of Pneumocystis carinii pneumonia may be achieved in the majority of cases by DNA detection using polymerase chain reaction on oropharyngeal mouth washes.

Joint effects of HIV-1 RNA levels and CD4 lymphocyte cells on the risk of specific opportunistic infections.

To evaluate the predictive value of baseline plasma HIV-1 RNA levels and CD4 lymphocyte counts and early changes in these markers after initiating antiretroviral therapy on the risk of development of specific opportunistic infections (OIs). Patient data from four antiretroviral therapy studies were combined for a retrospective analysis. The analysis included 842 participants from the virology substudies of these trials who had baseline measurements for both HIV-1 RNA levels and CD4 cell counts. Cox proportional hazards models were used to assess the joint effects of baseline CD4 cell count and HIV-1 RNA level and early treatment-associated changes in these values on the risk of development of Pneumocystis carinii pneumonia (PCP), cytomegalovirus (CMV), or Mycobacterium avium complex (MAC). The effects of potential confounders such as prior prophylaxis and previous OIs were also addressed. Baseline CD4 cell counts and HIV-1 RNA measurements showed significant associations with the risk of PCP, CMV, and MAC. Patients with higher levels of HIV-1 RNA were estimated to have three to six times the risk of these OIs than those with lower levels. Reductions in viral load were linked to significantly reduced risks of PCP, CMV, and MAC. Early decreases in RNA were generally more predictive of risk than were early increases in CD4 cell counts. Baseline viral load and reductions in viral load during therapy appeared to influence the risk of these OIs independently of the CD4 cell count. Future guidelines for the initiation of prophylaxis for these OIs may be improved by incorporating information on viral load.

Effect of smoking on the clinical progression of HIV-1 infection.

Cigarette smoking as a risk factor in progression of HIV-1 disease was investigated in the Multicenter AIDS Cohort Study of homosexual men. Longitudinal data for T-cell subsets, HIV-related clinical symptoms, smoking behavior, and AIDS medication use were collected semiannually from 2,499 HIV-1-seropositive men for up to 9 years. Survival methods, including Kaplan-Meier analysis and multivariate Cox regression models, were used to assess the effect of cigarette smoking on development of Pneumocystis carinii pneumonia (PCP), AIDS, death, and self-reported oral thrush. After adjustment for CD4+ lymphocyte count and use of antiretroviral and anti-PCP medications, smoking was not significantly associated with progression to PCP, AIDS, or death in either the HIV-seroprevalent or-seroincident cohort members. Among men who had baseline CD4+ cell counts > 200/microliter, smoking was associated with a 40% increase in the hazard of oral thrush (p < or = 0.01). These data indicate that cigarette smoking does not have a major effect on the progression of HIV-1 infection to AIDS or death but may affect the incidence of oral thrush.

Pneumocystis carinii Pneumonia in Patients Without Acquired Immunodeficiency Syndrome: Associated Illnesses and Prior Corticosteroid Therapy

To determine the clinical spectrum of immunosuppressive conditions and systemic corticosteroid therapy associated with the development of Pneumocystis carinii pneumonia in a consecutive series of patients without acquired immunodeficiency syndrome (AIDS). We retrospectively analyzed a consecutive series of 116 patients without AIDS who were assessed at Mayo Medical Center for a first episode of P. carinii pneumonia between 1985 and 1991. Medical records were examined to determine underlying immunosuppressive disorders, premorbid corticosteroid dosage and duration of therapy, associated infections, and subsequent respiratory failure and in-hospital mortality. Conditions associated with a first episode of P. carinii pneumonia were hematologic malignant disorders (30.2%), organ transplantation (25.0%), inflammatory disorders (22.4%), solid tumors (12.9%), and miscellaneous conditions (9.5%). Regardless of the associated underlying disease, corticosteroids had been administered systemically in 105 patients (90.5%) within 1 month before the diagnosis of P. carinii pneumonia. The median daily corticosteroid dose was equivalent to 30 mg of prednisone; however, 25% of patients had received as little as 16 mg of prednisone daily. The median duration of corticosteroid therapy was 12 weeks before the development of pneumonia; however, P. carinii pneumonia developed after 8 weeks or less of corticosteroid therapy in 25% of these patients. Respiratory failure occurred in 43%, and in-hospital mortality was 34% for patients with P. carinii pneumonia in conditions other than AIDS. Although these results do not suggest that premorbid administration of corticosteroids is the only factor that contributes to the development of P. carinii pneumonia in these patients, they show that, in this large consecutive series, systemic corticosteroid therapy, even in moderate doses, was administered to most patients during the month preceding the onset of P. carinii pneumonia. Consideration should be given to instituting P. carinii prophylaxis (when not contra-indicated) in patients for whom prolonged systemic corticosteroid therapy is prescribed.

Factors Associated with the Development of Pneumocystis carinii Pneumonia in 5,025 European Patients with AIDS

This study examined the factors associated with the development of a first episode of Pneumocystis carinii pneumonia (PCP) in 5,025 patients with AIDS, including 1,976 patients with primary PCP at the time of AIDS diagnosis and 635 with primary PCP occurring subsequently. Compared with untreated patients, patients treated with zidovudine were at similar risk of developing PCP during the first year of therapy but were at greater risk after longer intervals of treatment. The following factors were associated with an increased risk of PCP (either at the time of AIDS diagnosis or thereafter): lack of primary PCP prophylaxis, male homosexuality/bisexuality, diagnosis of AIDS in northern Europe, and CD4 cell count below 200 x 10(6)/L at the time of AIDS diagnosis. Patients with severe weight loss had a 60% higher risk of developing PCP during follow-up than those without such weight loss. Thus, the occurrence of PCP depended on geographic location, mode of acquisition of human immunodeficiency virus and AIDS, degree of immunodeficiency, and use of various treatment regimens.

Albendazole inhibits Pneumocystis carinii proliferation in inoculated immunosuppressed mice

Albendazole, a benzimidazole derivative widely used for treating helminth infections, was successfully used to treat and prevent development of Pneumocystis carinii pneumonia in transtracheally inoculated immunosuppressed mice. For treatment, 3 weeks postinoculation, albendazole at 300 and 600 mg/kg of body weight per day was administered in food for 3 weeks. For prophylaxis, albendazole was begun on the same day as inoculation at 300 mg/kg/day for 7 days, and then the dose was reduced to 150 mg/kg/day for 35 additional days. With these regimens, albendazole was effective both for treatment and prophylaxis. Both dexamethasone-immunosuppressed and L3T4+ monoclonal antibody-immunosuppressed mouse models were used, and albendazole inhibited P. carinii infection in both.

The development of Pneumocystis carinii pneumonia in germ-free rats requires immunosuppression and exposure to the Pneumocystis carinii organism

Adult germ-free rats treated with dexamethasone and exposed to a non-sterile environment did not harbor or develop Pneumocystis carinii cysts or trophozoites after 10 weeks of immunosuppression. Only when they were exposed to infected, conventional rats and treated with dexamethasone for 8 weeks or longer, did adult germ-free rats develop P. carinii infection.

Dysfunction of natural killer cells in human immunodeficiency virus-infected children with or without Pneumocystis carinii pneumonia

The development of Pneumocystis carinii pneumonia (PCP) in human immunodeficiency virus (HIV)-infected children with normal T-cell numbers is contrary to previous experience with HIV-infected adults, in whom low CD4+ T-cell numbers predict susceptibility to PCP. To determine whether PCP in HIV-infected children reflects a qualitative T-cell or other immune defect, we studied four HIV-infected children who also had PCP and 10 others without PCP for T-cell and natural killer (NK) cell function. Most of the HIV-infected children had normal T-cell numbers for age, and all had CD4+ T-cell numbers greater than those predictive of PCP in HIV-infected adults. All HIV-infected children had normal T-cell function in vitro. The HIV-infected children as a whole had deficient NK cell cytolysis. We obtained a significant interactive effect of age by health status for NK cell function between patients and age-matched control subjects. All HIV-infected children with defective NK cell function failed to enhance their NK cell cytolysis when their mononuclear cells were stimulated with recombinant interferon alfa (r-IFN-alpha). This NK cell defect in HIV-infected children may facilitate the development of secondary infection.

Racial and ethnic differences in outcome in zidovudine-treated patients with advanced HIV disease. Zidovudine Epidemiology Study Group

OBJECTIVES--To determine if racial-ethnic differences exist in survival, disease progression, and development of myelosuppression in zidovudine-treated patients with advanced human immunodeficiency virus (HIV) disease. DESIGN--Prospective observational study. -Hospital and private clinics in 12 metropolitan centers. -The study included 754 non-Hispanic white, 165 black, and 106 Hispanic patients with the acquired immunodeficiency syndrome (AIDS) or advanced AIDS-related complex (ARC) who received up to 2 years of zidovudine therapy. OUTCOME MEASURES--Survival, development of Pneumocystis carinii pneumonia (PCP), other opportunistic infections, and myelosuppression. RESULTS--At initiation of zidovudine therapy, Hispanic and particularly black patients had more advanced HIV disease than white patients, as indicated by lower baseline CD4+ counts, hematocrits, and AIDS-defining diagnoses. Black patients with AIDS also had a worse prognosis compared with white and Hispanic patients with AIDS. The product-limit survival rates at 2 years for white, black, and Hispanic patients with AIDS were 40%, 27%, and 39%, respectively (black vs white, P = .01; Hispanic vs white, P = .32, by the log-rank test). The respective proportions of patients who developed PCP at 2 years were 46%, 66%, and 44% (black vs white, P = .0001; Hispanic vs white, P = .86) and for other opportunistic infections the proportions were 56%, 63%, and 63%, respectively (black vs white, P = .03; Hispanic vs white, P = .09). There were no significant racial-ethnic differences in survival or in the development of opportunistic infections for patients with ARC, and there were no differences in the incidence of myelosuppression or dose reduction or suspension for patients with either ARC or AIDS. After adjusting for more advanced HIV disease (mainly low CD4+ counts and hematocrits), black race was no longer a significant independent predictor of survival. Adjustment for racial differences in the use of PCP prophylaxis accounted for most of the excess risk for the development of PCP in black patients compared with white patients with AIDS. CONCLUSIONS--Racial differences in survival and the development of opportunistic infections are mainly due to the more advanced HIV disease in black patients when zidovudine therapy is started and to their less frequent use of PCP prophylaxis. Innovative approaches are needed to ensure more widespread use of and earlier access to zidovudine therapy and PCP prophylaxis.

Racial and Ethnic Differences in Outcome in Zidovudine-Treated Patients With Advanced HIV Disease

OBJECTIVES--To determine if racial-ethnic differences exist in survival, disease progression, and development of myelosuppression in zidovudine-treated patients with advanced human immunodeficiency virus (HIV) disease. DESIGN--Prospective observational study.-Hospital and private clinics in 12 metropolitan centers.-The study included 754 non-Hispanic white, 165 black, and 106 Hispanic patients with the acquired immunodeficiency syndrome (AIDS) or advanced AIDS-related complex (ARC) who received up to 2 years of zidovudine therapy. OUTCOME MEASURES--Survival, development of Pneumocystis carinii pneumonia (PCP), other opportunistic infections, and myelosuppression. RESULTS--At initiation of zidovudine therapy, Hispanic and particularly black patients had more advanced HIV disease than white patients, as indicated by lower baseline CD4+ counts, hematocrits, and AIDS-defining diagnoses. Black patients with AIDS also had a worse prognosis compared with white and Hispanic patients with AIDS. The product-limit survival rates at 2 years for white, black, and Hispanic patients with AIDS were 40%, 27%, and 39%, respectively (black vs white, P = .01; Hispanic vs white, P = .32, by the log-rank test). The respective proportions of patients who developed PCP at 2 years were 46%, 66%, and 44% (black vs white, P = .0001; Hispanic vs white, P = .86) and for other opportunistic infections the proportions were 56%, 63%, and 63%, respectively (black vs white, P = .03; Hispanic vs white, P = .09). There were no significant racial-ethnic differences in survival or in the development of opportunistic infections for patients with ARC, and there were no differences in the incidence of myelosuppression or dose reduction or suspension for patients with either ARC or AIDS. After adjusting for more advanced HIV disease (mainly low CD4+ counts and hematocrits), black race was no longer a significant independent predictor of survival. Adjustment for racial differences in the use of PCP prophylaxis accounted for most of the excess risk for the development of PCP in black patients compared with white patients with AIDS. CONCLUSIONS--Racial differences in survival and the development of opportunistic infections are mainly due to the more advanced HIV disease in black patients when zidovudine therapy is started and to their less frequent use of PCP prophylaxis. Innovative approaches are needed to ensure more widespread use of and earlier access to zidovudine therapy and PCP prophylaxis.

Interaction of Cytokines and Alveolar Cells with Pneumocystis carinii In Vitro

Although deficient cellular immune function is a major predisposing factor in the development of Pneumocystis carinii pneumonia, the mechanisms involved in cellular immune surveillance against P. carinii have not been defined. When P. carinii were separated from rat cells by a semipermeable membrane, alveolar macrophages secreted substances lethal to P. carinii only when the macrophages were activated by interferon-gamma; normal macrophages were ineffective. Type II alveolar epithelial cells caused death of P. carinii whether or not interferon-gamma was present. The effects of soluble mediators also were tested; recombinant human tumor necrosis factor-alpha (TNF) but not recombinant rat interferon-gamma or endotoxin was directly lethal to P. carinii. These lethal effects were prevented when antiserum to TNF or antioxidants (catalase and superoxide dismutase) were included. These data suggest that TNF may be a major mediator involved in the killing activity of activated macrophages against P. carinii and that TNF's activity against P. carinii is related to induction of oxidative stresses.

Immunosuppression in a homosexual man with Kaposi's sarcoma

The occurrence of Kaposi's sarcoma in young homosexual men is a recently reported condition. The same individuals are at risk for the development of Pneumocystis carinii pneumonia and other unusual infections. These associations suggest these persons are somehow immunocompromised. Evidence of current or prior cytomegalovirus (CMV) infection is seen in a high percentage of these and other homosexual men. CMV infections are known to induce alterations in the immunoregulatory suppressor and helper T lymphocyte populations. The CMV infection is suspect as the cause of immunosuppression in these individuals. We present a case of Kaposi's sarcoma in a homosexual men with CMV cultured from his urine and semen. He showed a marked increase in his suppressor/cytotoxic cell (OKT8-positive) population, as well as a marked decrease in his helper cell (OKT4-positive) population. Mitogen and antigen studies demonstrated absent or markedly diminished response both in vitro and in vivo. Pokeweed mitogen (PWM)-induced IgG synthesis appeared normal. This patient, as well as the majority of other reported patients with this disease, manifested the HLA-Dr5 phenotype. The immunosuppression in this patient and possibly other similar men appears to be mediated by abnormalities in the immunoregulatory T lymphocytes.