[R01] An integrated approach to understand and diagnose congenital Chagas disease
Ente: National Institute of Allergy and Infectious Diseases
Scadenza: 2027-05-31
Importo max: 119.448 EUR
Paese: US
Descrizione
PROJECT SUMMARY/ABSTRACT
6-7 million people worldwide are infected with the parasite Trypanosoma cruzi, the agent of Chagas disease, including almost 300,000 in the United States (US). In recent years, Chagas disease has been increasingly recognized as an endemic problem, with about 10,000 Americans living with locally-acquired infection. Vertical transmission accounts for 22% of all new infections worldwide, and it is estimated that 22-108 infants are born with Chagas disease in the US every year. 5-10% of T. cruzi-infected women will transmit the infection to their newborns, causing a spectrum of disease in the infant: most infected infants are asymptomatic but up to 40% have involvement of the heart, brain, or liver. Congenital infection can also result in premature birth or perinatal death. Nearly a third of surviving infants will develop chronic cardiac and gastrointestinal problems later in life. Unfortunately, up to 75% of affected infants do not receive timely diagnosis or treatment; in the US, almost none are diagnosed at birth because of a lack of clinician awareness and guidelines for prenatal screening. Because treatment is safer and more effective during infancy than in later life, early diagnosis is critical. Our long-term goal is to accelerate the elimination of congenital Chagas disease globally and in the US by developing tools to predict and diagnose T. cruzi infections in infants. We propose to (1) identify clinical and epidemiological risk factors for vertical transmission; (2) investigate the pathogenesis of vertical transmission through the placenta using human and parasite genotyping transcriptomics; and (3) optimize and validate a new test for congenital T. cruzi infection using recombinase polymerase amplification (RPA), a DNA detection method that can be performed without advanced laboratory equipment or expertise and is adaptable to point-of-care platforms. To accomplish these goals, we propose a cohort study of pregnant women and their infants in Santa Cruz, Bolivia, where about 20% of pregnant women have Chagas disease; this is one on the only places in the world where it is possible to amass a sufficiently large cohort of infected mothers and infants in a single site. We hypothesize that by combining traditional epidemiological analyses with cutting-edge genomic techniques, we can better predict which infants born to T. cruzi-infected women are at highest risk of congenital infection. We also hypothesize that a new RPA assay will allow us to diagnose these infants more frequently and earlier than current standard diagnostics. In Aim 1, we will identify risk factors for vertical transmission in a cohort of T. cruzi-infected women to better identify high-risk infants. In Aim 2, we will characterize parasite genetic factors associated with vertical transmission of T. cruzi using genotyping and transcriptomics. Finally, in Aim 3, we will optimize our RPA assay and test it in the clinical setting to evaluate its ability
Istituzione: UNIV OF NORTH CAROLINA CHAPEL HILL
PI: Natalie McCarter Bowman
Progetto: 3R01AI151295-05S1
Settori: National Institute of Allergy and Infectious Diseases
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