Review of pharmacological options for the treatment of Chagas disease

Abstract

Introduction: Chagas disease (CD) is a worldwide problem, with over 8 million people infected in both rural and urban areas. CD was first described over a century ago, but only two drugs are currently available for CD treatment, benznidazole (BZN) and nifurtimox (NF). Treating CD infected patients, especially children and women of reproductive age, is vital in order to prevent long term sequelae, such as heart and gastrointestinal dysfunction, but this aim is still far from being accomplished. Currently, the strongest data to support benefit-risk considerations come from trials in children. Finally, treatment response biomarkers need further development as serology is being questioned as the best method to assess treatment response.Areas covered: This article is a narrative review on the pharmacology of drugs for CD, particularly BZN and NF. Data on drug biopharmaceutical characteristics, safety and efficacy of both drugs are summarized from a clinical perspective. Current data on alternative compounds under evaluation for CD treatment, and new possible treatment response biomarkers are also discussed. Conclusion:Early diagnosis and treatment of CD, especially in pediatric patients, is vital for an effective and safe use of the available drugs (i.e. BZN and NF). New biomarkers for CD are urgently needed for the diagnosis and evaluation of treatment efficacy, and to guide efforts from academia and pharmaceutical companies to accelerate the process of new drugs development.

Aspirin-triggered resolvin D1 reduces parasitic cardiac load by decreasing inflammation in a murine model of early chronic Chagas disease

“…However, adherence to treatment with these drugs may be compromised by adverse events that can force the discontinuation of the therapy [ 10 , 11 ]. Therefore, new approaches for treating this disease or improving the action of current antiparasitic drugs are needed [ 12 ].…”

Diagnostic Accuracy of Two Molecular Tools for Diagnosis of Congenital Chagas Disease

“…In fact, this should be considered by healthcare teams to eliminate the belief that people with Chagas disease are only those migrating from rural or historically endemic areas. Additionally, this reinforces the need to accomplish the guidelines of universal active screening for Chagas disease in pregnant women and their infants as well as to implement the treatment of women of a fertile age to prevent CCD transmission [3,28,29].…”

Recent Progress in the Development of Indole-Based Compounds Active against Malaria, Trypanosomiasis and Leishmaniasis

“…Despite AT having been discovered 112 years ago, AT treatment remains quite limited [ 16 ]. To date, there are only two available drugs, benznidazole ( 1 ) and nifurtimox ( 2 ) ( Figure 1 ), approved for clinical use more than 50 years ago [ 17 ]. Since then, little progress has been made in this area.…”

“…They are nearly 100% effective in curing or reducing parasitic burden in acute or early phases, in congenital cases and in reactivation in immunosuppressed patients [ 18 ]. However, their effectiveness is very restricted in chronic CD, and their advantages of use in these patients are still debatable [ 17 ]. These medications are also contraindicated during pregnancy or for people with renal or liver failure [ 17 ].…”

“…However, their effectiveness is very restricted in chronic CD, and their advantages of use in these patients are still debatable [ 17 ]. These medications are also contraindicated during pregnancy or for people with renal or liver failure [ 17 ]. Furthermore, these drugs offer other inconveniences for chronic AT management such as requirement of high dosage and prolonged period of treatment to achieve therapeutic efficacy, resulting in a wide range of side effects and consequent therapy discontinuation [ 19 , 20 ].…”