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      Clinical and translational research in Pneumocystis and Pneumocystis pneumonia* Translated title: La recherche clinique sur le Pneumocystis et la Pneumocystose pulmonaire

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          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”.

          Translated abstract

          La pneumocystose pulmonaire (PcP) est responsable d’une importante morbidité et mortalité chez les personnes immunodéprimées, particulièrement celles qui sont porteuses du virus de l’immunodéficience humaine (VIH). L’infection par le Pneumocystis s’observe de plus en plus, tant dans des populations immunodéprimées qu’immunocompétentes, et notamment chez des personnes atteintes de broncho-pneumopathies chroniques obstructives (BPCO). Cette mise au point recense les données récentes qui concernent la clinique de l’infection par le Pneumocystis, notamment la PcP, et les recommandations et les recherches en cours dans le domaine, telles qu’elles ont été présentées lors de la conférence commémorant le premier centenaire de la découverte de Pneumocystis.

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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

          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.

            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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              Epidemiology and clinical significance of pneumocystis colonization.

              Pneumocystis pneumonia has long been recognized as a cause of morbidity and mortality in immunocompromised populations, particularly those with HIV infection. Pneumocystis colonization-that is, detection of the organism or its DNA, without signs or symptoms of pneumonia-has recently been described, and accumulating evidence suggests that it may be an important clinical phenomenon. Sensitive molecular techniques such as polymerase chain reaction are frequently used to identify Pneumocystis colonization. Low levels of Pneumocystis in the lungs may stimulate pulmonary inflammation and may play a role in the development of lung diseases such as chronic obstructive pulmonary disease. In this review, we discuss evidence for the occurrence of Pneumocystis colonization in animals as well as the epidemiology and risk factors for Pneumocystis colonization in various human populations. We also evaluate the clinical significance of Pneumocystis colonization and its relationship to lung disease.

                Author and article information

                Parasite : journal de la Société Française de Parasitologie
                EDP Sciences
                February 2011
                15 February 2011
                : 18
                : 1 ( publisher-idID: parasite/2011/01 )
                : 3-11
                [1 ] Division of Pulmonary and Critical Care Medicine and HIV/AIDS Division, Department of Medicine, San Francisco General Hospital, University of California San Francisco USA
                Author notes
                [** ]Correspondence: Laurence Huang, M.D., HIV/AIDS Division, Ward 84, San Francisco General Hospital, 995 Potrero Avenue, San Francisco, CA 94110, USA Tel.: (415) 476-4082, extension 406 – Fax: (415) 476-6953 E-mail: lhuang@ 123456php.ucsf.edu
                parasite2011181p3 10.1051/parasite/2011181003
                © PRINCEPS Editions, Paris, 2011
                Page count
                Figures: 1, Tables: 1, Equations: 0, References: 52, Pages: 9


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