Chagas disease in immunocompromised patients

Abstract

SUMMARYAs Chagas disease remains prevalent in the Americas, it is important that healthcare professionals and researchers are aware of the screening, diagnosis, monitoring, and treatment recommendations for the populations of patients they care for and study. Management of Trypanosoma cruzi infection in immunocompromised hosts is challenging, particularly because, regardless of antitrypanosomal treatment status, immunocompromised patients with Chagas disease are at risk for T. cruzi reactivation, which can be lethal. Evidence-based practices to prevent and manage T. cruzi reactivation vary depending on the type of immunocompromise. Here, we review available data describing Chagas disease epidemiology, testing, and management practices for various populations of immunocompromised individuals, including people with HIV and patients undergoing solid organ and hematopoietic stem cell transplantation.

Keywords: Chagas disease; Trypanosoma cruzi; bone marrow transplantation; human immunodeficiency virus; immunocompromised hosts; organ transplantation.

Fig 1

The natural history of Chagas disease and impact of HIV-induced or iatrogenic immunosuppression. (Left) After a 1- to 2-week incubation period, the Trypanosoma cruzi-infected host enters the acute phase of Chagas disease, characterized by high parasitemia levels detectable by light microscopy. Symptoms are usually mild and nonspecific, and fewer than 1% of infections are recognized in the acute phase. (Center) Within 2–3 months, an effective immune response controls parasite replication and the patient passes into the chronic phase. Parasitemia becomes undetectable by microscopy and acute symptoms resolve. Subsequently, 70%–80% of individuals remain asymptomatic, whereas 20%–30% develop chronic end-organ disease, most frequently involving the heart. (Right) If a patient with chronic T. cruzi infection becomes immunosuppressed, impaired control of the parasite can lead to rising peripheral and tissue parasite loads, initially detectable by quantitative PCR in blood, later by microscopy, and culminating in symptomatic reactivation disease in the heart, skin, central nervous system, or other sites. Pre-emptive treatment prior to the onset of symptomatic reactivation is associated with favorable outcomes, while symptomatic reactivation can be rapidly lethal. Red line indicates T. cruzi parasitemia trend.

Fig 2

Simplified systemic cellular immune response to T. cruzi parasitemia. Naive CD8⁺ T cells engage MHC I molecules on antigen-presenting cells (APCs), activating the cytotoxic CD8 T cell response and INF-γ production against circulating T. cruzi trypomastigotes and host cells containing T. cruzi amastigotes. Naive CD4⁺ T cells engage MHC II molecules on APCs and become activated, leading to B cell activation and antibody response. Clones of the activated helper T cell, in turn, activate B cells and CD8⁺ T cells. If CD4 populations are impaired (e.g., in people with poorly controlled HIV), B-cell activation and antibody production may also be impaired, leading to inaccurate serologic testing results.