A Silenced Disease

Published by on March 11, 2022

Chagas disease is referred to as a silenced disease as it typically affects low-income communities, leading to a lack of motivation to find effective treatments (Alonso-Vega, et al., 2019). As a result, many people suffering with Chagas disease are driven into the cycle of poverty. This condition affects approximately 7 million people, mainly in Latin American countries; however, migration has led to the spread of this disease worldwide (Alonso-Vega, et al., 2019). It is caused by the protozoan parasite Trypanosoma cruzi (T. cruzi). It can be transmitted through vertical transmission between a mother and fetus, or through the feces/urine of the parasite’s intermediate host, the reduviid bug (Nguyen and Waseem, 2022). 

Chagas disease can occur as an acute or chronic infection. The acute phase is diagnosed through parasite detection in blood smears and immunoglobulin antibody tests (Teixeira, et al., 2006). Approximately 95% of patients with the acute phase are asymptomatic. The remaining 5% of symptomatic patients experience fever, malaise, muscle and joint pains, and respiratory disturbances (Teixeira, et al., 2006). The chronic phase is diagnosed through haemoculture and immunological assays. Chagas disease induces heart complications in approximately 94.5% of individuals diagnosed within the chronic phase, which can lead to further serious heart conditions such as arrhythmia (Teixeira, et al., 2006).

The lifecycle of the T. cruzi consists of four stages (Figure 1). In the first two stages, the parasite is replicative, and in the last two stages, it is infectious (Sales Junior, et al., 2017). During its infectious metacyclic trypomastigotes stage, it penetrates a wound inflicted by the reduviid bug or a mucous membrane, and then converts into amastigotes. Amastigotes convert into bloodstream trypomastigotes after many cycles of binary division in the gastrointestinal tract’s myocardium or myenteric plexus (Bonney, et al., 2019; Nguyen and Waseem, 2022). Bloodstream trypomastigotes then infect other cells, and the infection is spread through the blood (Sales Junior, et al., 2017). The body is able to control parasitic levels of T. cruzi by triggering innate and acquired immune responses during early stages of the infection. These responses require the use of macrophages, natural killer cells, natural killer T cells, and T and B lymphocytes to mediate the replication of T. cruzi (Machado et al., 2012). The infection also results in the production of two antibodies: diagnostic antibodies and lytic antibodies. Diagnostic antibodies help to identify the presence of the infection, while lytic antibodies result in the lysis of infective forms of T. cruzi to mediate replication (Machado, et al., 2012). 

Figure 1: The four stages of the T. cruzi lifecycle within vector (reduviid bug) and host (human). During its epimastigote stage, it remains in the gut of the insect. When it differentiates into its metacyclic trypomastigote stage, it becomes infectious and penetrates a wound to enter the body. It then converts into amastigotes. After many binary division cycles, it converts into trypomastigotes in the bloodstream and the infection is spread in the body through the blood (Onyekwelu, 2019).

While there are no vaccines for Chagas disease, two anti‐trypanosome drugs called nifurtimox and benznidazole are administered as treatment (Rajão, et al., 2014). These drugs are nitroheterocyclic compounds. Enzymatic nitroreduction results in the production of free radicals and electrophilic metabolites and these products react with nucleic acids to produce DNA lesions (Rajão, et al., 2014). The efficacy of these drugs is 50–80% in patients with acute infection, and 8–20% in patients with chronic infection (Sales Junior, et al., 2017). The adverse effects associated with the drugs include anorexia, paresthesia, gastrointestinal symptoms, and peripheral neuropathy.

Though prevalent, Chagas disease is characterized as a Neglected Tropical Disease by the World Health Organization (World Health Organization, 2019). It mainly affects populations in poor rural areas, leading to a lack of investment for an effective treatment. Our immune system does a great job to fight off the infection during its early stages, and present day technology allows us to test and identify the presence of the infection, whether it is in the acute stage or chronic stage. While there are drugs that exist to treat the disease, the numerous side effects and low efficacy during the chronic stage of the infection make them not ideal. This should encourage us to discover other candidates.

Bibliography:

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