Twenty-six percent of new Trypanosoma cruzi infections occur through mother-to-child transmission, and as vector and blood donation control improve, the proportion attributable to congenital infection will grow. An estimated 8 million persons have lifelong T. cruzi infection in Latin America. Approximately 5% of T. cruzi infected women give birth to infected infants at risk of clinically manifest Chagas disease at birth, shortly after birth or later in life. Laboratory-based screening is essential to detect congenital infection, and early detection is important to the most effective treatment. In high-prevalence areas, one promising approach may be universal newborn screening, as is routine for some genetic and metabolic disorders. However, there is no sufficiently sensitive, specific and logistically feasible test to diagnose congenital T. cruzi infection early in life, and current Latin American programs have low completion rates. The current standard for congenital T. cruzi diagnosis throughout Latin America relies on microscopy of concentrated cord blood, followed by serology at 9 months. In our previous study in Bolivia, we found a transmission rate of 6.5% (10/154 infants of infected mothers). However, none of the infected infants were detected by microscopy in cord blood, and only 40% were detected by microscopy in any of the 3 additional specimens collected in the first 30 days (a much more intensive sampling schedule than routine programs can sustain). Because hospitals lack beds, women are often discharged within 12-18 hours of delivery, complicating follow-up efforts. Prenatal screening with current rapid tests had only 90% sensitivity, and mothers with false-negative results seldom brought infants back for follow- up. We found that PCR-positive women were significantly more likely to transmit T. cruzi than seropositive women with negative PCR, and mothers of infected infants had significantly higher parasite loads. PCR detected 89% of infected infants at birth and100% by 30 days. Despite intensive efforts, only 58% of at-risk infants completed 9-month follow-up. We estimate that current screening programs miss more than half of all infected infants.
The aim of this application is to develop and evaluate novel techniques (Loop Mediated Isothermal Amplification, antigen detections assays and enhanced IgM assay for antibodies to Shed Acute Phase Antigens), with the ultimate aim of developing a rapid, point-of-care format to test neonates. In addition we will assess the use of prenatal PCR and T. cruzi-specific immune responses to identify the women with the highest risk of transmission, in order to ensure more intensive follow-up of their infants.

Public Health Relevance

Chagas disease causes more deaths in the Americas than any other parasitic disease, and women infected with the parasite can pass it to their infants during pregnancy. Current methods of diagnosis are poor, and infants are often left undiagnosed and can become very ill. In this application, we propose to test different methods of diagnosing Chagas disease in mothers and their infants, in order to begin early and appropriate treatment.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI087776-04
Application #
8451275
Study Section
Clinical Research and Field Studies of Infectious Diseases Study Section (CRFS)
Program Officer
Rao, Malla R
Project Start
2010-03-15
Project End
2015-02-28
Budget Start
2013-03-01
Budget End
2014-02-28
Support Year
4
Fiscal Year
2013
Total Cost
$537,760
Indirect Cost
$94,490
Name
Johns Hopkins University
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Castro-Sesquen, Yagahira E; Gilman, Robert H; Galdos-Cardenas, Gerson et al. (2014) Use of a novel chagas urine nanoparticle test (chunap) for diagnosis of congenital chagas disease. PLoS Negl Trop Dis 8:e3211
Castro-Sesquen, Yagahira E; Gilman, Robert H; Yauri, Veronica et al. (2013) Detection of soluble antigen and DNA of Trypanosoma cruzi in urine is independent of renal injury in the guinea pig model. PLoS One 8:e58480
Castro-Sesquen, Yagahira E; Gilman, Robert H; Yauri, Veronica et al. (2011) Cavia porcellus as a model for experimental infection by Trypanosoma cruzi. Am J Pathol 179:281-8
Garcia, H H; Gonzalez, A E; Rodriguez, S et al. (2010) Neurocysticercosis: unraveling the nature of the single cysticercal granuloma. Neurology 75:654-8