Colonización por Pneumocystis Jirovecii en embarazadas y su posible implicación en la prematuridad y el aborto espontáneo

Antecedentes: Pneumocystis jirovecii es un hongo atípico, ubicuo, con tropismo pulmonar y gran estenoxenismo cuya principal vía de transmisión es aérea. Se considera un patógeno oportunista que causa neumonía grave en pacientes inmunodeprimidos, habiendo sido ampliamente investigado en el contexto de la infección por VIH. La utilización de herramientas de diagnóstico molecular ha permitido demostrar la presencia de Pneumocystis en sujetos que no presentan manifestaciones clínicas ni radiológicas de neumonía, situación conocida como colonización. Un estudio previo ha puesto de manifiesto la presencia de este microorganismo en las mujeres embarazadas como un grupo susceptible a la colonización. Existen evidencias que llevan a pensar que la colonización por Pneumocystis podría jugar un papel importante en la fisiopatología de diversas enfermedades por su capacidad, demostrada en modelos animales, de inducir en fases muy tempranas de la infección activación de macrófagos alveolares con elevación de interleuquinas proinflamatorias. La demostración por parte de nuestro grupo en pacientes con EPOC colonizados de un aumento en la respuesta inflamatoria sistémica, junto con la reciente evidencia de la capacidad de transmitirse verticalmente y la elevada tasa de infección documentada en abortos espontáneos obligan a plantear el posible papel que P. jirovecii puede desempeñar a través de estos mecanismos en la alteración del desarrollo normal del embarazo. Población y métodos: Para abordar esta cuestión se ha desarrollado un estudio clínico observacional donde se han incluido 82 gestantes, con sus respectivos recién nacidos, de los que se obtuvieron datos clínicos y muestras biológicas respiratorias y sanguíneas después de obtener el correspondiente consentimiento informado. Como grupo control se incluyeron 36 mujeres en edad fértil no embarazadas. Además se incluyeron en el estudio 26 muestras de tejido placentario procedentes de partos a término y 20 muestras de placentas procedentes de abortos espontáneos con el correspondiente tejido fetal. La detección de la presencia de colonización por Pneumocystis se realizó utilizando técnicas moleculares específicas en los diferentes tipos de muestras. Se completó el estudio utilizando técnicas de metagenómica para identificar la micobiota presente en mayo el tejido placentario y se realizaron los correspondientes estudios histológicos utilizando técnicas de tinción convencionales. Resultados: Los datos obtenidos revelan una tasa de colonización significativamente mayor en mujeres embarazadas en el momento del parto de un 39% (46,9% en el caso de parto prematuro; 27,3% en parto a término) frente a un 13,9% en mujeres no gestantes en edad fértil. En los recién nacidos también encontramos tasas de colonización elevadas, del 33,3% en prematuros y del 23,1% en recién nacidos a término, observándose concordancia entre la presencia de colonización en la madres y sus recién nacidos. La tasa de colonización en los recién nacidos al aumentar las semanas de gestación sigue una distribución decreciente, similar a la de la madre. En este estudio también se identificó ADN de Pneumocystis en el 50% de las placentas a término, en el 55 % de las placentas procedentes de abortos y en un 70 % de fetos. La identificación de otras especies de hongos mediante técnicas de metagenómica pone de manifiesto la existencia de una microbiota fúngica en la placenta donde predomina P. jirovecci y pueden estar presentes otros hongos como Cladosporium spp. Conclusiones: Este estudio muestra una elevada tasa de colonización por Pneumocystis jirovecii en gestantes en el momento del parto identificando el embarazo como un factor de riesgo para la colonización. Se observa una elevada concordancia en la colonización por Pneumocystis entre las madres y sus recién nacidos, sugiriendo una transmisión vertical desde las gestantes a sus hijos. Además se demuestra una asociación significativa entre la presencia de colonización por Pneumocystis en las gestantes y una reducción en la duración del embarazo, asociación que se mantiene al evaluar en un análisis multivariante otras circunstancias como la edad de las madres o la presencia de diabetes o hipertensión, lo que sugiere que la colonización por Pneumocystis durante el embarazo podría representar un factor de riesgo de prematuridad, y probablemente de aborto, ignorado hasta ahora que abre una nueva línea de investigación que podría contribuir a mejorar la salud tanto de las gestantes como de sus recién nacidos

Update on Dihydropteroate Synthase (DHPS) Mutations in Pneumocystis jirovecii

A Pneumocystis jirovecii is one of the most important microorganisms that cause pneumonia in immunosupressed individuals. The guideline for treatment and prophylaxis of Pneumocystis pneumonia (PcP) is the use of a combination of sulfa drug-containing trimethroprim and sulfamethoxazole. In the absence of a reliable method to culture Pneumocystis, molecular techniques have been developed to detect mutations in the dihydropteroate synthase gene, the target of sulfa drugs, where mutations are related to sulfa resistance in other microorganisms. The presence of dihydropteroate synthase (DHPS) mutations has been described at codon 55 and 57 and found almost around the world. In the current work, we analyzed the most common methods to identify these mutations, their geographical distribution around the world, and their clinical implications. In addition, we describe new emerging DHPS mutations. Other aspects, such as the possibility of transmitting Pneumocystis mutated organisms between susceptible patients is also described, as well as a brief summary of approaches to study these mutations in a heterologous expression system

Multilocus Genotyping of Pneumocystis jirovecii from Deceased Cuban AIDS Patients Using Formalin-Fixed and Paraffin-Embedded Tissues

The results of the genotypic characterization of Pneumocystis jirovecii are described in lung tissue samples from 41 Cubans who died of AIDS with pneumocystosis between 1995 and 2008. Histological sections of the lung preserved as formalin-fixed and paraffin-embedded tissue were examined. PCR amplification and nucleotide sequencing of the two mitochondrial genes (large and small) of the pathogen allowed verification of a predominance of genotype 3 (85T/248C) of the large mitochondrial gene and genotype 3 (160A/196T) of the small mitochondrial gene over a period of 14 years (1995–2008). These results suggest that the 85T/248C//160A/196T genotype circulates with the highest frequency (81.3%) among AIDS patients in Cuba. Multilocus analysis indicates a limited circulation of pathogen genotypes on the island with the existence of a clonal genotype with an epidemic structure. Furthermore, it appears that circulating strains of P. jirovecii have not developed mutations related to sulfonamide resistance. Taken together, the data in this study revealed important elements about pneumocystosis in Cuban patients dying of AIDS and the usefulness of formalin-fixed and paraffin-embedded samples to carry out molecular epidemiology studies of P. jirovecii

High prevalence of Pneumocystis jirovecii pneumonia among Mozambican children < 5 years of age admitted to hospital with clinical severe pneumonia

We aimed to describe Pneumocystis jirovecii pneumonia (PCP) prevalence and features in children from sub-Saharan Africa, and to investigate PCP-associated risk factors. During 2006-2007 we used molecular methods to test children younger than 5 years old admitted with severe pneumonia to a hospital in Southern Mozambique for Pneumocystis infection. We recruited 834 children. PCP prevalence was 6.8% and HIV prevalence was 25.7%. The in-hospital and delayed mortality were significantly higher among children with PCP (20.8% vs. 10.2 %, p=0.021, and 11.5% vs. 3.6%, p=0.044, respectively). Clinical features were mostly overlapping between the two groups. Independent risk factors for PCP were age less than a year (OR 6.34, 95%CI 1.86-21.65), HIV infection (OR 2.99, 95%CI 1.16-7.70), grunting (OR 2.64, 95%CI 1.04-6.73), and digital clubbing (OR 10.75, 95%CI 1.21-95.56). PCP is a common and life-threatening cause of severe pneumonia in Mozambican children. Mother-to-child HIV transmission prevention should be strengthened. Better diagnostic tools are needed

Hypothetical Pneumocystis jirovecii Transmission from Immunocompetent Carriers to Infant

Revue en accès libre via : http://www.cdc.gov/ncidod/eid/index.htmInternational audienc

Congenital cytomegalovirus, parvovirus and enterovirus infection in Mozambican newborns at birth: A cross-sectional survey

BACKGROUND: Congenital cytomegalovirus (cCMV) infection is the most prevalent congenital infection acquired worldwide, with higher incidence in developing countries and among HIV-exposed children. Less is known regarding vertical transmission of parvovirus B19 (B19V) and enterovirus (EV). We aimed to assess the prevalence of CMV, B19V and EV vertical transmission and compare results of screening of congenital CMV obtained from two different specimens in a semirural Mozambican maternity. METHODS: A cross sectional study was conducted among pregnant mothers attending Manhica District Hospital upon delivery. Information on maternal risk factors was ascertained. Dried umbilical cord (DUC) samples were collected in filter paper for CMV, B19V and EV detection by real-time polymerase chain reaction (RT-PCR), and nasopharyngeal aspirates (NPA) to test for CMV by RT-PCR. Maternal blood samples and placental biopsy samples were also obtained to investigate CMV maternal serology, HIV status and immunopathology. RESULTS: From September 2014 to January 2015, 118 mothers/newborn pairs were recruited. Prevalence of maternal HIV infection was 31.4% (37/118). CMV RT-PCR was positive in 3/115 (2.6%) of DUC samples and in 3/96 (6.3%) of NPA samples obtained from neonates. The concordance of the RT-PCR assay through DUC with their correspondent NPA sample was moderate (Kappa = 0.42 and p<0.001. No differences on cCMV prevalence were found among HIV-exposed and unexposed. All (100%) mothers were seropositive for CMV IgG. RT-PCR of EV and B19V in DUC were both negative in all screened cases. No histological specific findings were found in placental tissues. No risk factors associated to vertical transmission of these viral infections were found. CONCLUSIONS: This study indicates the significant occurrence of vertical transmission of CMV in southern Mozambique. Larger studies are needed to evaluate the true burden, clinical relevance and consequences of congenital infections with such pathogens in resource-constrained settings

Pneumocystis jirovecii Transmission from Immunocompetent Carriers to Infant

We report a case of Pneumocystis jirovecii transmission from colonized grandparents to their infant granddaughter. Genotyping of P. jirovecii showed the same genotypes in samples from the infant and her grandparents. These findings support P. jirovecii transmission from immunocompetent carrier adults to a susceptible child

High prevalence of Pneumocystis jirovecii pneumonia among Mozambican children <5 years of age admitted to hospital with clinical severe pneumonia

We aimed to describe Pneumocystis jirovecii pneumonia (PCP) prevalence and features in children from sub-Saharan Africa and to investigate PCP-associated risk factors. During 2006–2007 we used molecular methods to test children younger than 5 years old admitted with severe pneumonia to a hospital in southern Mozambique for Pneumocystis infection. We recruited 834 children. PCP prevalence was 6.8% and HIV prevalence was 25.7%. The in-hospital and delayed mortality were significantly higher among children with PCP (20.8% vs. 10.2%, p 0.021, and 11.5% vs. 3.6%, p 0.044, respectively). Clinical features were mostly overlapping between the two groups. Independent risk factors for PCP were age less than a year (odds ratio (OR) 6.34, 95% confidence interval (CI) 1.86–21.65), HIV infection (OR 2.99, 95% CI 1.16–7.70), grunting (OR 2.64, 95% CI 1.04–6.73) and digital clubbing (OR 10.75, 95% CI 1.21–95.56). PCP is a common and life-threatening cause of severe pneumonia in Mozambican children. Mother-to-child HIV transmission prevention should be strengthened. Better diagnostic tools are needed.This work was supported by the World Health Organization (WHO-C6-181-489). QB has a fellowship from the program Miguel Servet of the ISCIII (Plan Nacional de I+D+I 2008–2011, grant CP11/00269). LM has a fellowship from the program Río Hortega of the ISCIII (CM13/00260).Peer reviewe