HIV-associated Pneumocystis pneumonia.
ABSTRACT During the past 30 years, major advances have been made in our understanding of HIV/AIDS and Pneumocystis pneumonia (PCP), but significant gaps remain. Pneumocystis is classified as a fungus and is host-species specific, but an understanding of its reservoir, mode of transmission, and pathogenesis is incomplete. PCP remains a frequent AIDS-defining diagnosis and is a frequent opportunistic pneumonia in the United States and in Europe, but comparable epidemiologic data from other areas of the world that are burdened with HIV/AIDS are limited. Pneumocystis cannot be cultured, and bronchoscopy with bronchoalveolar lavage is the gold standard procedure to diagnose PCP, but noninvasive diagnostic tests and biomarkers show promise that must be validated. Trimethoprim-sulfamethoxazole is the recommended first-line treatment and prophylaxis regimen, but putative trimethoprim-sulfamethoxazole drug resistance is an emerging concern. The International HIV-associated Opportunistic Pneumonias (IHOP) study was established to address these knowledge gaps. This review describes recent advances in the pathogenesis, epidemiology, diagnosis, and management of HIV-associated PCP and ongoing areas of clinical and translational research that are part of the IHOP study and the Longitudinal Studies of HIV-associated Lung Infections and Complications (Lung HIV).
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ABSTRACT: DNA from phylogenetically diverse microbes is routinely recovered from healthy human lungs and used to define the lung microbiome. The proportion of this DNA originating from microbes adapted to the lungs, as opposed to microbes dispersing to the lungs from other body sites and the atmosphere, is not known. We use a neutral model of community ecology to distinguish members of the lung microbiome whose presence is consistent with dispersal from other body sites and those that deviate from the model, suggesting a competitive advantage to these microbes in the lungs. We find that the composition of the healthy lung microbiome is consistent with predictions of the neutral model, reflecting the overriding role of dispersal of microbes from the oral cavity in shaping the microbial community in healthy lungs. In contrast, the microbiome of diseased lungs was readily distinguished as being under active selection. We also assessed the viability of microbes from lung samples by cultivation with a variety of media and incubation conditions. Bacteria recovered by cultivation from healthy lungs represented species that comprised 61% of the 16S rRNA-encoding gene sequences derived from bronchoalveolar lavage samples. IMPORTANCE : Neutral distribution of microbes is a distinguishing feature of the microbiome in healthy lungs, wherein constant dispersal of bacteria from the oral cavity overrides differential growth of bacteria. No bacterial species consistently deviated from the model predictions in healthy lungs, although representatives of many of the dispersed species were readily cultivated. In contrast, bacterial populations in diseased lungs were identified as being under active selection. Quantification of the relative importance of selection and neutral processes such as dispersal in shaping the healthy lung microbiome is a first step toward understanding its impacts on host health. Copyright © 2015 Venkataraman et al.mBio 01/2015; 6(1). DOI:10.1128/mBio.02284-14 · 6.88 Impact Factor
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ABSTRACT: The diagnosis of patients with pulmonary infiltrates and human immunodeficiency virus (HIV) infection remains a challenge. In current clinical practice the gold standard for Pneumocystis jirovecii pneumonia (PCP) diagnosis remains the identification of the organism in broncoalveolar lavage (BAL) using microscopy (e.g., silver stain). (1->3)-β -D-glucan (BG) is a polysaccharide that is present within the cell wall of Pneumocystis and other fungi. We analyzed serum and BAL lavage fluid from a cohort of 119 patients that did have HIV, a diagnosis of pneumonia and underwent bronchoscopy (FOB) for diagnosis of PCP. The discriminative power of serum BG for the diagnosis of PCP in this group of patients was very high. Using a cutoff of 300 pg/mL, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 91%, 92%, 89% and 93% respectively. A model for ROC with just serum BG (N = 108) had an AUC of 0.95. Serum procalcitonin (PCT) and BAL BG were not as accurate for the diagnosis of PCP. For BAL BG using a cutoff of 783 pg/mL, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 72%, 79%, 72% and 79% respectively. The differences between the medians for serum PCT between the group with a without PCP did not reach statistical significance (p=0.6137). The measurement of serum BG should be incorporated in the diagnostic work up of HIV positive patients with dyspnea and infiltrates on chest X ray. Our study confirms the diagnostic value of serum BG previously reported by others but we add a cutoff value that we believe is more accurate for patients with AIDS and suspicion of PCP.Respiratory Medicine 10/2014; 108(11). DOI:10.1016/j.rmed.2014.09.017 · 2.92 Impact Factor
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ABSTRACT: Pneumocystis jirovecii is a common opportunistic infection in the HIV-positive population and is re-emerging as a growing clinical concern in the HIV-negative immunosuppressed population. Newer targeted immunosuppressive therapies and the discovery of rare genetic mutations have furthered our understanding of the immunity required to clear Pneumocystis infection. The immune system can also mount a pathologic response against Pneumocystis following removal of immunosuppression and result in severe damage to the host lung. The current review will examine the most recent epidemiologic studies about the incidence of Pneumocystis in the HIV-positive and HIV-negative populations in the developing and developed world and will detail methods of diagnosis for Pneumocystis pneumonia. Finally, this review aims to summarize the known mediators of immunity to Pneumocystis and detail the pathologic immune response leading to Pneumocystis-related immune reconstitution inflammatory syndrome.Seminars in Immunopathology 11/2014; 37(2). DOI:10.1007/s00281-014-0459-z · 6.48 Impact Factor