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Treatment of Chagas disease

W Apt

University of Chile, Santiago, Chile

Chapter Outline

Introduction 751

Drugs which inhibit protein or purine synthesis 752 Inhibitors of ergoesterol 753 Ofloxacine 755

Inhibitors of trypanothione metabolism 756 Inhibitors of cysteine protease (CPI) 758 Inhibitors of phospholipids 758 Inhibitors of pyrophosphate metabolism 758 Natural drugs 759 Other drugs 760

Treatment of human infection 760

Current drug therapy 760 Acute cases 762 Congenital infection 762 Accidental Chagas disease 764 Organ transplants 764

Reactivations of chronic Chagas disease and treatment of Chagas disease in immunosuppressed patients 764

Evaluation and follow-up of specific therapy 765 Resistance of T. cruzi to drugs 765 Critical comments 766 Glossary 767 References 767

Introduction

Chagas disease has existed for at least 9000 years. Of the desiccated human mummies from coastal valley sites in northern Chile and Peru, 41% were found to be positive by polymerase chain reaction (PCR) and hybridization probes for kDNA of Trypanosoma cruzi. These tissue extracts correspond to the cultural groups that lived from 7000 BC to 1500 AD. These findings confirm that the sylvatic animal cycle of Chagas disease was well established by that time.1

American Trypanosomiasis Chagas Disease. DOI: http://dx.doi.org/10.1016/B978-0-12-801029-7.00032-0

Copyright © 2017 Elsevier Inc. All rights reserved.

Table 31.1 Drugs administered from 1940 to 1975 to laboratory animals and Chagas disease patients which produced a reduction of the parasitemia but not a parasitological cure

8 Aminoquinolines (Primaquine)

Bisquinaldines (Bayer 7602)

Arsenebenzenes (Spirotrypan)

Fenantridines (Cardibium)

Emetine and derivatives

Nitrofurans and derivates

Nitroimidazole and derivatives

Piperazine and derivatives

Triphenylmethane

Triaminoquinazolines

2-Acetamide-5-nitrodiazole

Source: Adapted from Brener Z. Terapeutica experimental na doenca de Chagas. En: Brener Z, Andrade Z,

Barral-Neto M, editors. Trypanosoma cruzi e Doenca de Chagas. Rio de Janeiro, Brazil: Guanabara Koogan; 2000.

p. 379-88.

Although Chagas disease is an old zoonosis, its treatment is recent. The present human treatment with nifurtimox (NF) and benznidazole (BZN) dates from the 1970s and is based on an empirical therapy.2-4

There are several drugs which act in vitro on Trypanosma cruzi, in cultures of epimastigotes and trypomastigotes, tissue cultures of amastigote forms, and in vivo in different species of infected animals with diverse strains (subpopulations) of the parasite. It is important to point out that the drugs used in Chagas disease therapy must have an effect on the intracellular amastigote forms, which are the reproductive forms in the vertebrate host. The epimastigote and trypomastigote forms of these hosts derive from the amastigotes, and for this reason their response to different drugs has less importance.5,6 In Table 31.1 several drugs are described that were empirically applied to T. cruzi in experiments on animals and humans between 1940 and 1975. With the majority of these drugs a decrease of the parasitemia and lethality may be obtained, but not a parasitological cure.7

 
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