Target product profile for a test for the early assessment of treatment efficacy in chagas disease patients: An expert consensus

Abstract

The absence of a test for the early assessment of treatment efficacy, often called atest of cure (ToC), is a major obstacle to Chagas disease control. Accurately monitoring treatment response would undoubtedly improve patient management and support the conduct of clinical trials. Although treatment efficacy and treatment response may be conceptually different, we are using these terms synonymously for the purpose of the current target product profile(TPP).Unfortunately, there is no gold-standard test for the early determination of whether someone who has been treated for chronic Chagas disease has been cured or not. Current methods used for monitoring Chagas disease treatment efficacy are suboptimal due to the fact that: (1) clinical progression of the disease is silent and associated with complex and mostly unknown host?pathogen interactions; (2) once in the chronic stage, infected subjects remain seropositive for years, with very low and intermittent parasitemia counts; and (3) as a consequence, in the chronic phase, parasitological detection methods have very low sensitivity, whereas molecular detection can only be done in reference laboratories. Besides, clinical evaluation may not be specific to Chagas disease and cannot be used in cases where some structural tissue damagealready exists. In addition, measuring seroconversion by conventional tests is not viable as it may take years or decades for a patient with chronic disease to revert serologically. Finally, the posttreatment detection of circulating parasites (through their DNA) by molecular amplification techniques, such as quantitative polymerase chain reaction (qPCR), may be useful for determining treatment failure, but a negative qPCR result cannot be considered a surrogate of cure.Development of a test that can determine in a timely manner if a patient treated for Chagas disease has successfully responded to treatment has therefore been identified as a priority.As mentioned above, such a test could be used in two different scenarios or use cases: (1) the daily clinical management (DCM) of Chagas disease patients posttreatment to decide if and/or when a patient should be followed up after treatment completion and (2) in the context of clinical trials (CT), where the test would be used as the endpoint measurement for the evaluation of new anti?T. cruzi treatments.The development of this test (or tests) should be guided by a TPP. TPPs for a test to assess treatment response in Chagas disease patients have been suggested previously. Building on them, we now present a TPP specifically describing the required technical and performance characteristics of a test to determine if a Chagas disease patient has been cured posttreatment. We have considered two use scenarios: day-to-day healthcare provision and clinical evaluation of new anti?T. cruzi drugs or alternative regimens of the drugs currently available.