Chagas' Disease: Treatment, drugs

There are several problems. The drugs have an unsatisfactory cure rate. The chronic lesions may be caused by auto-immune mechanisms and might not be improved by eradicating parasites. [Nevertheless the role of auto-immune mechanisms should not be exaggerated: the disease worsens during immune suppression as in transplantation and in HIV]. The drugs should be given long term. Results vary from country to country, possibly due to a difference in sensitivity of the parasites. Side effects occur, more often in adults than in children. It is best to avoid steroids and possibly tetracyclines, since these may exacerbate the infection.

• Nifurtimox (Lampit®) 5 mg/kg/day orally, slowly increased to 15 mg/kg/day (divided over 3 doses) for 2 to 4 months. The drug is no longer produced. Side effects: neurotoxicity (insomnia, tremor, polyneuritis), nausea, leukopaenia, thrombocytopaenia or hypersensitivity. May cause haemolysis in G6PD deficiency [glucose-6-phosphate dehydrogenase]. In the acute phase the parasites disappear from the blood in 80 % to almost 100 % of cases. The actual cure rate is 50-60%.

• Benznidazole (syn. benzonidazole: Radanil®, Ragonil®, Rochagan®), 5-10 mg/kg/day orally for 1 to 2 months. Administration (generally 100 mg tablets) is twice daily. The same side effects as nifurtimox, but less frequent and less pronounced, although skin rash occurs relatively frequently (up to 30% of patients), sometimes accompanied by swollen lymph nodes. The pharmaceutical company Roche has donated all commercial rights and the technology to manufacture benznidazole to the Brazilian government.

• Allopurinol (Zyloric®): 600 mg/day orally for 2 months (adult dose). The place of this therapy has not yet been determined, but it is currently used following flare-ups after heart transplantation.

• Experimental: D0870 (a bis-triazole derivative), posaconazole, squalene oxidase inhibitors such as terbinafine, proteasome inhibitors, trans-sialidase inhibitors.

• T. cruzi is auxotrophic for polyamine biosynthesis, since it does not have ornithine decarboxylase, and is thus naturally refractory to the effects of eflornithine.

  
  

In the chronic phase the usefulness of these drugs is doubtful, but the tendency is more and more towards treatment. Symptomatic therapy is indicated: oesophageal sphincter dilation, extramucosal cardiotomy (Heller’s operation), colon surgery. An experimental treatment is the endoscopic injection of botulin toxin into the distal oesophageal sphincter (e.g. 20 U into each quadrant).

In heart failure, diuretics, ACE-inhibitors and antiarrhythmic drugs may be beneficial. Beta-blockers are best avoided in view of the AV-conduction problems and bradyarrhythmias. Anticoagulants are indicated for patients with atrial fibrillation, previous embolic phenomena and apical aneurysms. Amiodarone (Cordarone®) is effective in more than 50% of patients who develop ventricular extrasystoles or ventricular tachycardia. A bifascicular or trifascicular conduction block, also a second or third degree AV-block are contra-indications. Amiodarone is an iodine-containing Vaughan-Williams class III antiarrhythmic drug. It may cause thyroid problems (either hypothyroidism or hyperthyroidism). Reversible deposits in the cornea, pulmonary toxicity, neuropathy, photosensitivity and grey discoloration of the skin may occur. The elimination half-life varies greatly from individual to individual (20 to 100 days). A high incidence of "torsades de pointes" has been observed during use of quinidine, disopyramide and other class I antiarrhythmic drugs. Patients with cardiac problems are generally very sensitive to digitalis (lower dose necessary). Pacemakers and cardiac surgery are reserved in practice for those with financial means and these persons have an inherently low risk of infection. Pacemakers can be used in cases of severe bradyarrhythmia. Implantation of an automatic defibrillator is indicated for patients with recurrent ventricular tachycardia or a history of cardiac arrest.

Category: Medicine Notes