# Unraveling the cytokine profile in acute Chagas disease in the Brazilian Amazon: Insights before and after treatment

## TL;DR

This study examines immune responses in acute Chagas disease patients in the Brazilian Amazon before and after treatment, finding significant cytokine changes and improved immune profiles post-treatment.

## Contribution

The study provides new insights into cytokine dynamics and treatment efficacy in acute Chagas disease, particularly in the context of oral transmission outbreaks.

## Key findings

- Elevated cytokine levels in acute-phase patients before treatment indicate immune activation.
- Post-treatment cytokine profiles resembled healthy controls, suggesting effective immune modulation.
- Certain cytokines correlated with cardiac fibrosis markers, emphasizing the need for long-term monitoring.

## Abstract

Chagas disease (CD) is a neglected anthropozoonosis caused by Trypanosoma cruzi, with the oral route standing out as the primary cause for the increase in acute cases in the Brazilian Amazon and a key factor in the increase of acute cases. Despite this, the immune response in affected individuals remains minimally explored in humans. This longitudinal study aimed to characterize the serum cytokine profile in patients with acute CD before and after treatment. Participants were recruited from several municipalities in the state of Amazonas, and individuals with chronic inflammatory diseases were excluded. The cytokines IL-1α, IL-2, IL-4, IL-5, IL-6, IL-10, IL-17α, TNF-α, and IFN-γ were analyzed. From 2017 to 2022, 35 patients and 14 controls were included (mean age 46.3 ± 17.8 years; 57.1% male; 74.3% from oral transmission outbreaks). Twenty-five patients (71.4%) were successfully followed up, despite logistical challenges. Elevated levels of all cytokines were found in acute-phase patients before treatment, indicating an effective immune activation. After an average of 12 months post-treatment, significant reductions were observed in IL-6 (p < 0.001), TNF-α (p = 0.011), IFN-γ (p < 0.001), and IL-10 (p = 0.015). IL-2 showed strong correlations with IL-1α and IL-17α in the acute phase (r = 0.91 and 0.95). Post-treatment cytokine profiles resembled those of the control group, suggesting treatment efficacy in modulating inflammation. IL-17α, IL-10, and IL-2 maintained an interesting pattern after treatment. Cardiac MRI revealed myocardial injury by late gadolinium enhancement (LGE) in 27.3% of pre-treatment and 33.3% of post-treatment patients. IL-1α, IL-17α, and IL-4 had moderate negative correlations (r = –0.36 to –0.67) with LGE. These results highlight the importance of monitoring the inflammatory response in the long term, as well as the observed cytokine modulation, which reinforces the hypothesis of not only a favorable acute immune response but also a sustained long-term clinical improvement following treatment.

Chagas disease is caused by Trypanosoma cruzi and remains a neglected tropical disease with increasing reports of acute cases in the Brazilian Amazon, largely due to oral transmission. Although the clinical aspects of acute CD are well described, the immune response during and after treatment is still poorly described in human studies. In this longitudinal study, we analyzed the serum cytokine profiles of patients diagnosed with acute CD in Amazonas, Brazil, before and after benznidazole treatment. Our results show that cytokine levels—particularly IL-6, TNF-α, IFN-γ, and IL-10—were significantly elevated during the acute phase and decreased after treatment, suggesting effective immune modulation. Interestingly, IL-2 strongly correlated with IL-1α and IL-17α during the acute phase, and the post-treatment cytokine profile resembled that of healthy controls. Cardiac MRI revealed myocardial injury by LGE in a subset of patients before and after treatment, highlighting the need for long-term follow-up. Certain cytokines, such as IL-1α, IL-17α, and IL-4, also showed negative correlations with cardiac fibrosis markers. This study emphasizes the value of monitoring immune responses beyond the acute phase; these findings also offer insights into the disease progression and support the hypothesis that early treatment not only controls infection but may also promote sustained clinical and immunological recovery.