Comparing in vivo bioluminescence imaging and the Multi-Cruzi immunoassay platform to develop improved Chagas disease diagnostic procedures and biomarkers for monitoring parasitological cure
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Published:2022-10-03
Issue:10
Volume:16
Page:e0010827
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ISSN:1935-2735
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Container-title:PLOS Neglected Tropical Diseases
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language:en
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Short-container-title:PLoS Negl Trop Dis
Author:
Francisco Amanda Fortes,
Saade Ursula,
Jayawardhana Shiromani,
Pottel Hans,
Scandale Ivan,
Chatelain Eric,
Liehl Peter,
Kelly John M.ORCID,
Zrein Maan
Abstract
Background
Chagas disease is caused by the protozoan parasite Trypanosoma cruzi and is a serious public health problem throughout Latin America. With 6 million people infected, there is a major international effort to develop new drugs. In the chronic phase of the disease, the parasite burden is extremely low, infections are highly focal at a tissue/organ level, and bloodstream parasites are only intermittently detectable. As a result, clinical trials are constrained by difficulties associated with determining parasitological cure. Even highly sensitive PCR methodologies can be unreliable, with a tendency to produce “false-cure” readouts. Improved diagnostic techniques and biomarkers for cure are therefore an important medical need.
Methodology/Principal findings
Using an experimental mouse model, we have combined a multiplex assay system and highly sensitive bioluminescence imaging to evaluate serological procedures for diagnosis of T. cruzi infections and confirmation of parasitological cure. We identified a set of three antigens that in the context of the multiplex serology system, provide a rapid, reactive and highly accurate read-out of both acute and chronic T. cruzi infection. In addition, we describe specific antibody responses where down-regulation can be correlated with benznidazole-mediated parasite reduction and others where upregulation is associated with persistent infection. One specific antibody (IBAG39) highly correlated with the bioluminescence flux and represents a promising therapy monitoring biomarker in mice.
Conclusions/Significance
Robust, high-throughput methodologies for monitoring the efficacy of anti-T. cruzi drug treatment are urgently required. Using our experimental systems, we have identified markers of infection or parasite reduction that merit assessing in a clinical setting for the longitudinal monitoring of drug-treated patients.
Funder
Drugs for Neglected Diseases initiative
UK Aid, UK
Directorate-General for International Cooperation (DGIS), The Netherlands
Swiss Agency for Development and Cooperation, Switzerland
Médecins Sans Frontières (Doctors Without Borders), International.
Publisher
Public Library of Science (PLoS)
Subject
Infectious Diseases,Public Health, Environmental and Occupational Health
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