Pathogenesis and Symptoms

T. cruzi is primarily transmitted to humans and other mammals by Triatomine insect vectors, also known as "kissing bugs." The parasite infects cells and tissues including muscle and nervous tissue. In the acute phase shortly after transmission, symptoms may include swelling of the eyelids, fever, headaches, and enlargement of the liver and spleen. However, most acute infections are asymptomatic or mild.

Years or decades later, approximately 30% of chronically infected individuals will develop potentially life-threatening cardiac or gastrointestinal clinical manifestations. Cardiac problems include heart dilatation and congestive heart failure. Gastrointestinal manifestations involve swelling of the esophagus or colon. Without treatment, Chagas disease can be lifelong and life-threatening.

Available Treatment Options

Currently there are two drugs approved for Chagas Disease Treatment - benznidazole and nifurtimox. Both are nitroheterocyclic compounds that have activity against the parasite by disrupting its metabolism. Benznidazole is the preferred first-line treatment due to its slightly better tolerability profile. The standard treatment duration is 60 days.

Treatment during the acute and early chronic phases is highly effective, curing over 60-90% of cases. However, efficacy declines significantly in the later chronic indeterminate and symptomatic stages. Adverse drug reactions including rashes, peripheral neuropathy and gastrointestinal upset are common with both benznidazole and nifurtimox. Close medical monitoring during treatment is important.

Research on New Treatments

Given the limitations of benznidazole and nifurtimox, new treatment options are desperately needed. Research efforts have explored candidates such as posaconazole, a drug already approved for fungal infections. Early clinical trials showed promising safety and efficacy against chronic Chagas infection. Larger phase 3 studies are still ongoing.

Other investigation has focused on repurposing existing drugs either alone or in combination. Anti-retroviral drugs and antibiotics such as itraconazole have shown varying degrees of activity against T. cruzi in vitro and animal models. Combination therapy may offer advantages of reduced toxicity and resistance. Early clinical data on fosravuconazole and benznidazole showed similar cure rates to benznidazole alone.

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