Central nervous system commitment in Chagas disease

Abstract

The involvement of the central nervous system (CNS) during human acute and chronic Chagas disease (CD) has been largely reported. Meningoencephalitis is a frequent finding during the acute infection, while during chronic phase the CNS involvement is often accompanied by behavioral and cognitive impairments. In the same vein, several studies have shown that rodents infected with Trypanosoma cruzi (T. cruzi) display behavior abnormalities, accompanied by brain inflammation, in situ production of pro-inflammatory cytokines and parasitism in diverse cerebral areas, with involvement of microglia, macrophages, astrocytes, and neurons. However, the mechanisms used by the parasite to reach the brain remain now largely unknown. Herein we discuss the evidence unravelling the CNS involvement and complexity of neuroimmune interactions that take place in acute and chronic CD. Also, we provide some clues to hypothesize brain infections routes in human and experimental acute CD following oral infection by T. cruzi, an infection route that became a major CD related public health issue in Brazil.

Outcomes of patients in Chagas disease of the central nervous system: a systematic review

“…The parasite shows an apparent affinity for supratentorial structures in the anterior/middle cranial fossa, such as the frontal and parietal lobes, which is associated with inflammation leading to tissue damage. This inflammation could affect the pyramidal tract which is responsible for motor function, potentially resulting in hemiparesis or hemiplegia (Useche et al ., 2022).…”

“…In this context, it's worth noting that they may exhibit neurological symptoms such as seizures. This can make challenging, in some cases, to conclusively attribute reported clinical manifestations solely to T. cruzi infection without considering the potential influence of HIV-related effects (Zaporojan et al, 2018).…”

“…Approximately 20–40% of infected individuals progress to a symptomatic chronic phase, primarily characterized by organ involvement, with cardiomyopathy being the most common, followed by the development of megavisceral manifestations, such as megaoesophagus and megacolon (Bern, 2015; Pérez-Molina and Molina, 2018). One of the complications of Chagas disease is the presence of the parasite in the central nervous system (CNS) in the acute phase or due to reactivation during chronic disease (Useche et al ., 2022). This reactivation is particularly prevalent in immunocompromised patients (Cordova et al ., 2008; Clark and Bern, 2021; Useche et al ., 2022).…”

“…One of the complications of Chagas disease is the presence of the parasite in the central nervous system (CNS) in the acute phase or due to reactivation during chronic disease (Useche et al ., 2022). This reactivation is particularly prevalent in immunocompromised patients (Cordova et al ., 2008; Clark and Bern, 2021; Useche et al ., 2022). CNS Chagas disease exhibits varying mortality rates depending on the disease phase, with mortality near 10% in the acute disease and 79–100% during reactivation (Pittella, 2009; Pérez-Molina et al ., 2011).…”

“…Common clinical signs and symptoms observed in patients with cerebral Chagas include confusion, headache, hypertonia, convulsions, meningismus, focal neurological deficits, fever and altered mental status (Pittella, 1993; Córdova et al ., 2013). The diagnosis of cerebral Chagas disease is challenging, typically involves direct observation of parasitic forms in the cerebrospinal fluid (CSF), blood or tissue biopsies (Córdova et al ., 2013; Useche et al ., 2022). Chagas disease reactivation in the CNS can manifest as acute diffuse meningoencephalitis or as a mass-occupying abscess-like lesion (chagoma) in 75–90% of the patients (Cordova et al ., 2008; Córdova et al ., 2013).…”