What is Chagas disease?
Chagas disease, also known as American trypanosomiasis, is a parasitic infection caused by the protozoan Trypanosoma cruzi. The parasite is primarily transmitted by triatomine bugs, known commonly as “kissing bugs”, with additional modes of transmission through blood transfusions, organ transplants, and from mother to child during pregnancy or childbirth.
Symptoms of Chagas disease
Initial symptoms of Chagas disease usually appear within 8–10 weeks after infection and can include swelling around the site of infection, fever, body aches, headache, rash, loss of appetite, diarrhea, and vomiting. However, most people do not experience any symptoms at this acute stage. In later stages, symptoms can develop in 10-30% of infected individuals and involve the heart, esophagus, or colon. Heart symptoms may include cardiac enlargement and heart failure. Digestive system symptoms usually involve an enlarged esophagus or colon.
Available treatment options
There are currently two drugs available for Chagas Disease Treatment – benznidazole and nifurtimox. Both drugs were developed in the 1970s but have significant side effects and are only effective in curing the infection if given during the acute and early chronic phases of the disease.
Benznidazole
Benznidazole is currently the first-line treatment recommended by the World Health Organization (WHO) for Chagas disease. It is available as tablets that are taken twice daily for 60 days for adults and children weighing more than 20 kg. The major side effects include rash, gastrointestinal symptoms (nausea, vomiting, diarrhea), and neurological symptoms like peripheral neuropathy. Side effects generally diminish after treatment is completed. Benznidazole works by interfering with the parasite’s DNA and RNA. Studies have shown it can cure the infection in 60-85% of cases if given shortly after infection in the acute stage and 40-60% if given during the early chronic phase.
Nifurtimox
Nifurtimox is an alternative drug used to treat Chagas disease that is available as tablets to be taken three times daily for 90-120 days. Common side effects include gastrointestinal symptoms, neurological effects, and skin rashes. It works by releasing harmful nitroanion metabolites that damage the parasite’s cell membranes. Nifurtimox has similar cure rates to benznidazole during the acute stage but may be more effective in certain regions of South America. It remains an acceptable second-line treatment option.
Limitations of current treatment options
While benznidazole and nifurtimox can successfully cure Chagas disease if given early, they have limited efficacy in chronically infected individuals. Success rates drop to less than 50% in chronic cases over many years’ duration. This is partly due to the parasites developing resistance to the drugs and formation of tissue stages that are not as readily targeted by available medicines. Other drawbacks include the lengthy treatment durations, potential serious side effects, and lack of pediatric formulations. As a result, most infected individuals remain untested and untreated. New drugs are urgently needed to address these limitations.
Promising new treatment candidates
A new drug pipeline for Chagas disease has emerged in recent decades with several potential candidates in clinical development. Some of the most promising include:
– E1224: Currently in Phase II trials, E1224 is a nitroheterocyclic compound similar to nifurtimox but may have higher cure rates and fewer side effects.
– Fexinidazole: This oral nitroimidazole completed Phase III trials with high cure rates against both acute and chronically infected patients. It has received regulatory approval in several countries and WHO prequalification.
– SCYX-7158: This orally bioavailable compound acts by inhibiting the parasite’s sterol 14α-demethylase, showing safety and strong efficacy in preclinical studies. Phase I trials are underway.
– Acoziborole: This first-in-class benzoxaborole acts on the parasite’s prohibitin proteins and successfully cured mice in preclinical research. Phase I studies have started.
With several candidates in human clinical trials, new safer and more effective drugs for chronic Chagas disease may become available in the next 5-10 years. This would significantly improve treatment outcomes for the millions currently infected globally.
*Note:
1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it
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