Clinical and translational research inPneumocystisandPneumocystis pneumonia

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Abstract

Pneumocystis pneumonia (PcP) remains a significant cause of morbidity and mortality in immunocompromised persons, especially those with human immunodeficiency virus (HIV) infection. Pneumocystis colonization is described increasingly in a wide range of immunocompromised and immunocompetent populations and associations between Pneumocystis colonization and significant pulmonary diseases such as chronic obstructive pulmonary disease (COPD) have emerged. This mini-review summarizes recent advances in our clinical understanding of Pneumocystis and PcP, describes ongoing areas of clinical and translational research, and offers recommendations for future clinical research from researchers participating in the “First centenary of the Pneumocystis discovery”.

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Most cited references 37

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Early Antiretroviral Therapy Reduces AIDS Progression/Death in Individuals with Acute Opportunistic Infections: A Multicenter Randomized Strategy Trial

Andrew Zolopa, Janet Andersen, Lauren Komarow … (2009)

Background Optimal timing of ART initiation for individuals presenting with AIDS-related OIs has not been defined. Methods and Findings A5164 was a randomized strategy trial of “early ART” - given within 14 days of starting acute OI treatment versus “deferred ART” - given after acute OI treatment is completed. Randomization was stratified by presenting OI and entry CD4 count. The primary week 48 endpoint was 3-level ordered categorical variable: 1. Death/AIDS progression; 2. No progression with incomplete viral suppression (ie HIV viral load (VL) ≥50 copies/ml); 3. No progression with optimal viral suppression (ie HIV VL <50 copies/ml). Secondary endpoints included: AIDS progression/death; plasma HIV RNA and CD4 responses and safety parameters including IRIS. 282 subjects were evaluable; 141 per arm. Entry OIs included Pneumocytis jirovecii pneumonia 63%, cryptococcal meningitis 12%, and bacterial infections 12%. The early and deferred arms started ART a median of 12 and 45 days after start of OI treatment, respectively. The difference in the primary endpoint did not reach statistical significance: AIDS progression/death was seen in 20 (14%) vs. 34 (24%); whereas no progression but with incomplete viral suppression was seen in 54 (38%) vs. 44 (31%); and no progression with optimal viral suppression in 67 (48%) vs 63 (45%) in the early vs. deferred arm, respectively (p = 0.22). However, the early ART arm had fewer AIDS progression/deaths (OR = 0.51; 95% CI = 0.27–0.94) and a longer time to AIDS progression/death (stratified HR = 0.53; 95% CI = 0.30–0.92). The early ART had shorter time to achieving a CD4 count above 50 cells/mL (p<0.001) and no increase in adverse events. Conclusions Early ART resulted in less AIDS progression/death with no increase in adverse events or loss of virologic response compared to deferred ART. These results support the early initiation of ART in patients presenting with acute AIDS-related OIs, absent major contraindications. Trial Registration ClinicalTrials.gov NCT00055120

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Pneumocystis carinii pneumonia. Differences in lung parasite number and inflammation in patients with and without AIDS.

K Offord, James Smith, J. C. Juan … (1989)

Pneumocystis carinii pneumonia has emerged as a significant cause of morbidity and mortality in immunocompromised patients with and without AIDS. To determine differences in P. carinii pneumonia in patients with and without AIDS, the P. carinii parasite numbers, lung inflammatory cell populations, gas exchange, and survival were assessed in a series of 75 consecutive patients with P. carinii pneumonia. Bronchoalveolar lavage was used to quantify the parasite and inflammatory cell numbers in these patients. The data from this study indicate: (1) patients with P. carinii pneumonia and AIDS have significantly greater numbers of P. carinii per ml of lavage compared to other immunocompromised patients with P. carinii pneumonia (p less than 0.0001); (2) patients with P. carinii pneumonia and AIDS also have significantly fewer neutrophils recovered in the lavage compared to other immunocompromised patients with P. carinii pneumonia (p = 0.0001); (3) patients with AIDS and P. carinii pneumonia have higher arterial oxygen tensions than those patients with P. carinii pneumonia in conditions other than AIDS (p = 0.008); and (4) increased lavage neutrophils (rather than parasite number) correlate with poorer oxygenation and poorer patient survival (p = 0.01). This investigation demonstrates substantial differences in lung inflammation and parasite number during P. carinii pneumonia in patients with and without AIDS. The data further suggest that lung inflammation contributes substantially to respiratory impairment in patients with P. carinii pneumonia.

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Early predictors of mortality from Pneumocystis jirovecii pneumonia in HIV-infected patients: 1985-2006.

Simon Edwards, Alison D. Grant, Jeff Miller … (2008)

Pneumocystis jirovecii pneumonia (PCP) remains the leading cause of opportunistic infection among human immunodeficiency virus (HIV)-infected persons. Previous studies of PCP that identified case-fatality risk factors involved small numbers of patients, were performed over few years, and often focused on patients who were admitted to the intensive care unit. The objective of this study was to identify case-fatality risk factors present at or soon after hospitalization among adult HIV-infected patients admitted to University College London Hospitals (London, United Kingdom) from June 1985 through June 2006. We performed a review of case notes for 494 consecutive patients with 547 episodes of laboratory-confirmed PCP. Overall mortality was 13.5%. Mortality was 10.1% for the period from 1985 through 1989, 16.9% for the period from 1990 through June 1996, and 9.7% for the period from July 1996 through 2006 (P = .142). Multivariate analysis identified factors associated with risk of death, including increasing patient age (adjusted odds ratio [AOR], 1.54; 95% confidence interval [CI], 1.11-2.23; P = .011), subsequent episode of PCP (AOR, 2.27; 95% CI, 1.14-4.52; P = .019), low hemoglobin level at hospital admission (AOR, 0.70; 95% CI, 0.60-0.83; P < .001), low partial pressure of oxygen breathing room air at hospital admission (AOR, 0.70; 95% CI, 0.60-0.81; P < .001), presence of medical comorbidity (AOR, 3.93; 95% CI, 1.77-8.72; P = .001), and pulmonary Kaposi sarcoma (AOR, 6.95; 95% CI, 2.26-21.37; P = .001). Patients with a first episode of PCP were sicker (mean partial pressure of oxygen at admission +/- standard deviation, 9.3+/-2.0 kPa) than those with a second or third episode of PCP (mean partial pressure of oxygen at admission +/- standard deviation, 9.9+/-1.9 kPa; P = .008), but mortality among patients with a first episode of PCP (12.5%) was lower than mortality among patients with subsequent episodes of PCP (22.5%) (P = .019). No patient was receiving highly active antiretroviral therapy before presentation with PCP, and none began highly active antiretroviral therapy during treatment of PCP. Mortality risk factors for PCP were identifiable at or soon after hospitalization. The trend towards improved outcome after June 1996 occurred in the absence of highly active antiretroviral therapy.

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Journal

Title: Parasite

Abbreviated Title: Parasite

Publisher: EDP Sciences

ISSN (Print): 1252-607X

ISSN (Electronic): 1776-1042

Publication date Created: February 2011

Publication date (Print): February 2011

Volume: 18

Issue: 1

Pages: 3-11

Article

DOI: 10.1051/parasite/2011181003

SO-VID: 0c39767a-cd55-4197-99f7-d45baacf44d2

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This work is licensed under a Creative Commons Attribution 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

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ScienceOpen disciplines: Parasitology,Life sciences

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ScienceOpen disciplines: Parasitology, Life sciences

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