Chagas disease: Present status of pathogenic mechanisms and chemotherapy

Abstract

There are approximately 7.8 million people in Latin America, including Chile, who suffer from Chagas disease and another 28 million who are at risk of contracting it. Chagas is caused by the flagellate protozoan Trypanosoma cruzi. It is a chronic disease, where 20%-30% of infected individuals develop severe cardiopathy, with heart failure and potentially fatal arrhythmias. Currently, Chagas disease treatment is more effective in the acute phase, but does not always produce complete parasite eradication during indeterminate and chronic phases. At present, only nifurtimox or benznidazole have been proven to be superior to new drugs being tested. Therefore, it is necessary to find alternative approaches to treatment of chronic Chagas. The current treatment may be rendered more effective by increasing the activity of anti-Chagasic drugs or by modifying the host's immune response. We have previously shown that glutathione synthesis inhibition increases nifurtimox and benznidazole activity. In addition, there is increasing evidence that cyclooxygenase inhibitors present an important effect on T. cruzi infection. Therefore, we found that aspirin reduced the intracellular infection in RAW 264.7 cells and, decreased myocarditis extension and mortality rates in mice. However, the long-term benefit of prostaglandin inhibition for Chagasic patients is still unknown.

Curcumin Enhances the Anti-Trypanosoma cruzi Activity of Benznidazole-Based Chemotherapy in Acute Experimental Chagas Disease

“…This finding is consistent with the antiparasitic activity of this combination, since it is natural that a reduction in parasitemia and the parasite load is accompanied by a reduction in IFN-␥ levels, as the inflammatory process associated with the infection undergoes resolution (46,47). In contrast, IL-4 levels were higher in all the treatment groups.…”

Concomitant Benznidazole and Suramin Chemotherapy in Mice Infected with a Virulent Strain of Trypanosoma cruzi

“…Since research and development of new specific medicines have been neglected for too many years, Bz remains the reference drug against T. cruzi infection. Strong evidence indicates that during Bz enzymatic processing by the NADPH-cytochrome P-450 system (5,(31)(32)(33), the production of highly reactive electrophilic metabolites overcomes the redox balance of T. cruzi, based on the enzyme dihydrotrypanothione T(SH) 2 , disrupting parasite metabolism and viability (29,33). The role of Sur in T. cruzi metab- Cardiac samples were collected 24 h after the last treatment.…”

“…Although chemotherapy with Bz is not always successful, no drugs with therapeutic efficiency superior to that of Bz are available (5)(6)(7). Clinical studies have also reported marked side effects of Bz associated with low specificity and systemic toxicity (1,5). These limitations have highlighted the need for more effective and suitable strategies for Chagas disease control (1,7).…”

“…Since the 1960s, the compound N-benzyl-2-nitroimidazole acetamide (benznidazole [Bz]) has been the first-line drug against T. cruzi infection. Although chemotherapy with Bz is not always successful, no drugs with therapeutic efficiency superior to that of Bz are available (5)(6)(7). Clinical studies have also reported marked side effects of Bz associated with low specificity and systemic toxicity (1,5).…”

Eficacia de nifurtimox para el tratamiento de pacientes con enfermedad de Chagas crónica

“…En la actualidad sólo existen dos fármacos específi cos para el tratamiento de esta enfermedad, los cuales fueron desarrollados hace más de 30 años, uno de ellos es nifurtimox 5 . Este fármaco, un análogo de nitrofuranos, actúa como tripanocida contra todas las formas de T. cruzi 6,7 . El tratamiento de la enfermedad de Chagas se recomienda durante todas sus fases, como también en pacientes con SIDA, trasplante de órganos o que reciben fármacos inmunosupresores, los cuales presentan mayor…”