Project: Recognition of the primary infection by pneumosystis in infants: A silent threat to public health

Increasing evidence suggests that the most common respiratory infection affecting infants is the mild and stealth, primary infection by the microfungal organism Pneumocystis. This infection goes currently unrecognized and has been neglected as a subclinical irrelevant infection by contrast with the severe Pneumocystis pneumonia affecting the immunocompromised host. However, compelling new evidence suggests that this infection may be pathogenic to certain infant age groups and that microbiomehost interactions in early life may condition the development of altered immune responses in older infants or adults. They underscore the importance of understanding this highly prevalent subclinical Pneumocystis primary infection. This infection is acquired close to birth, develops over a period of few weeks, and peaks between the ages of 2 to 5 months. Furthermore, this age interval period coincides with the peak of infant respiratory morbidity and postneonatal mortality, raising the hypothesis that a pathogenic role of Pneumocystis in infants is possible provided the nearuniversal prevalence of this infection at that particular age window. This hypothesis is strengthened by the recent demonstration of pathology consisting of increased mucus associated to Pneumocystis in infant lungs in line with observations in animal models from us and other research groups that show Pneumocystisassociated transient respiratory impairment and airway remodelling. Importantly, Pneumocystis h a s b e e n detected in lung of aborted fetuses, wich may suggest vertical transmission and an eventual cofactor role in abortion and in newborn respiratory distress due to the demonstrated abiility of Pneumocystis to decrease pulmonary surfactant. Therefore this proposal aims to recognize the epidemiology of this silent infection in preterm and term otherwise healthy newborns and small infants in different countries, to recommend a preferred method for diagnosis by comparing senstivity of available methods of known specificity, to characterize the pulmonary mycomicrobiome using metagenomic analyses, and additionally, to understand the Pneumocystisairway epithelium interaction using transcriptomic studies to identify the hostactivated gene responses associated to this unique fungal pathogen in infant lung specimens. The proposal will importantly explore Pneumocystisassociated breathprints using noninvasive detection of volatile organic compounds (VOC) in exhaled air that may prove as an ideal method to recognize stealth infections especially in prematures and small infants. Recognition of the wide distribution of Pneumocystis epidemiology will be in itself a measure of success of this proposal and, furthermore, understanding this early life infant-microbial interaction may lead to prevent infant and, additionally, older age respiratory morbidity. Therefore results of this proposal will contribute to prevent infectiousrelated morbidity and promote well-being, by increasing our recognition and understanding of this early-life and highly frequent Pneumocystis primary infection.

Acronym	CAPRI (Reference Number: ELAC2014/HID-0254)
Duration	01/01/2015 - 01/01/2018
Project Topic	Prevention infectious diseases & wellbeing
Project Results (after finalisation)	not yet available
Network	ERANet-LAC
Call	ERANet-LAC 1st Joint Call on Research and Innovation between the EU Member States and Associated Countries and the Community of Latin American and Caribbean States (CELAC)

Project partner

Number	Name	Role	Country
1	Universidad de Chile	Coordinator	Chile
2	B&S Analytik GmbH	Partner	Germany
3	Valencian Region Foundation for the Promotion of Health and Biomedical Research	Partner	Spain
4	Instituto de Biomedicina de Sevilla	Partner	Spain
5	University of Brest and University Hospital of Brest	Partner	France