Características clínicas, diagnósticas y pronosticas de pacientes con neumonía por Pneumocystis jiroveci en individuos infectados por virus de inmunodeficiencia humana e individuos inmunocomprometidos por otra etiología: comparative study of cases in HIV-infected patients and immunocompromised non-HIV-infected patients

Cerón, Inés; Rabagliati, Ricardo; Langhaus, Javiera; Silva, Felipe; Guzmán, Ana María; Lagos, Marcela

doi:10.4067/s0716-10182014000400007

Cited by 13 publications

(13 citation statements)

References 22 publications

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“…In our study, the failure to use qPCR would have led to misdiagnosis of 22 cases of probable PCP in HIV-negative patients. Similarly, Cerón et al found that the diagnosis of PCP in 45 HIV-negative patients was based on qPCR in 93% of the cases (26). Another example is the study of Mühlethaler et al, which would have missed 16.6% of patients with probable PCP if they had not used qPCR (16).…”

Section: Discussionmentioning

confidence: 99%

Impact of HIV Infection Status on Interpretation of Quantitative PCR for Detection of Pneumocystis jirovecii

et al. 2015

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Quantitative PCR (qPCR) is now a key diagnostic tool forPneumocystispneumonia. However, cutoffs to distinguish between infected and colonized patients according to their HIV status have not yet been determined. According to clinical, radiological, and biological data, we retrospectively classified bronchoalveolar lavage (BAL) samples subjected to qPCR over a 3-year period into four categories, i.e., definite PCP, probable PCP,Pneumocystiscolonization, and no infection. Fungal burden was then analyzed according to the HIV status of the patients. Among 1,212 episodes of pneumonia screened in immunocompromised patients, 52 and 27 HIV-positive patients were diagnosed with a definite and probable PCP, whereas 4 and 22 HIV-negative patients had definite and probable PCP, respectively. Among patients with definite or a probable PCP, HIV-negative patients had a significantly lower burden than HIV-positive patients (P< 10−4). In both groups, the median fungal burden was significantly higher in patients with definite PCP than in colonized patients. A single cutoff at 1.5 × 104copies/ml allowed to differentiate colonized and infected HIV-positive patients with 100% sensitivity and specificity. In HIV-negative patients, cutoff values of 2.87 × 104and 3.39 × 103copies/ml resulted in 100% specificity and sensitivity, respectively. Using cutoffs determined for the whole population would have led us to set aside the diagnosis of PCP in 9 HIV-negative patients with definite or probable PCP. qPCR appeared to be the most sensitive test to detectPneumocystisin BAL samples. However, because of lower inocula in HIV-negative patients, different cutoffs must be used according to the HIV status to differentiate between colonized and infected patients.

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Section: Discussionmentioning

confidence: 99%

Impact of HIV Infection Status on Interpretation of Quantitative PCR for Detection of Pneumocystis jirovecii

et al. 2015

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“…In addition, patients with chronic inflammatory conditions are also showing increased infections due to concomitant corticosteroid therapy and other immunomodulators (8). Patients in these non-HIV-positive categories fare worse than those with HIV (9–11). The mainstay of PCP treatment and prophylaxis has long been trimethoprim-sulfamethoxazole (TMP-SMX).…”

Section: Introductionmentioning

confidence: 95%

Functional Characterization of Pneumocystis carinii Inositol Transporter 1

Cushion

Collins

Sesterhenn

et al. 2016

mBio

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Fungi in the genus Pneumocystis live in the lungs of mammals, where they can cause a fatal pneumonia (PCP [Pneumocystis pneumonia]) in hosts with compromised immune systems. The absence of a continuous in vitro culture system for any species of Pneumocystis has led to limited understanding of these fungi, especially for the discovery of new therapies. We recently reported that Pneumocystis carinii, Pneumocystis murina, and most significantly, Pneumocystis jirovecii lack both enzymes necessary for myo-inositol biosynthesis but contain genes with homologies to fungal myo-inositol transporters. Since myo-inositol is essential for eukaryotic viability, the primary transporter, ITR1, was functionally and structurally characterized in P. carinii. The predicted structure of P. carinii ITR1 (PcITR1) contained 12 transmembrane alpha-helices with intracellular C and N termini, consistent with other inositol transporters. The apparent Km was 0.94 ± 0.08 (mean ± standard deviation), suggesting that myo-inositol transport in P. carinii is likely through a low-affinity, highly selective transport system, as no other sugars or inositol stereoisomers were significant competitive inhibitors. Glucose transport was shown to use a different transport system. The myo-inositol transport was distinct from mammalian transporters, as it was not sodium dependent and was cytochalasin B resistant. Inositol transport in these fungi offers an attractive new drug target because of the reliance of the fungi on its transport, clear differences between the mammalian and fungal transporters, and the ability of the host to both synthesize and transport this critical nutrient, predicting low toxicity of potential inhibitors to the fungal transporter.

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“…La presentación clínica de la neumonía por P. jiroveci difiere en sus características entre individuos con infección por VIH de aquellos inmunocomprometidos por otras causas 3 . En pacientes sin infección por VIH el diagnóstico es más difícil y con una mortalidad cercana a 40%, muy superior al 10% descrito en pacientes con infección por VIH 9 . El cuadro clínico más común de la neumonía por P. jiroveci en pacientes con infección por VIH es el inicio subagudo de disnea, fiebre, tos y malestar general, que empeora con los días o semanas.…”

Section: Discussionunclassified

“…Se ha descrito compromiso de pabellón auricular, coroides, retina, tiroides, paratiroides, hígado, bazo, páncreas, riñón, uréteres, glándulas adrenales, corazón, tráquea, ganglios linfáticos, pleura, líquido ascítico, orina, médula ósea, músculos, hipófisis, meninges, corteza cerebral, tracto gastrointestinal, incluyendo un caso de perforación de intestino delgado 17 . El sitio más frecuente de compromiso extrapulmonar corresponde a los ganglios linfáticos [6][7][8][9][10][11][12][13][14][15][16] . La vía de diseminación puede ser hematógena, linfática, y también por contigüidad como en casos descritos de neumonía por P. jiroveci con derrame pleural concomitante [6][7][8][9][10][11][12][13][14][15][16] .…”

Section: Discussionunclassified

“…El sitio más frecuente de compromiso extrapulmonar corresponde a los ganglios linfáticos [6][7][8][9][10][11][12][13][14][15][16] . La vía de diseminación puede ser hematógena, linfática, y también por contigüidad como en casos descritos de neumonía por P. jiroveci con derrame pleural concomitante [6][7][8][9][10][11][12][13][14][15][16] . El diagnóstico de neumocistosis extrapulmonar no es difícil una vez que es considerado como diagnóstico diferencial, sin embargo, rara vez es sospechado por su baja frecuencia, presentación clínica no específica que puede ser atribuido a una amplia variedad de otras infecciones o enfermedades oportunistas que ocurren en pacientes con VIH e inmunocompromiso grave 6,20,21 .…”

Section: Discussionunclassified

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