Home Economics American Trypanosomiasis Chagas Disease, Second Edition: One Hundred Years of Research
Diffuse chagasic meningoencephalitis should be included in the differential diagnosis of other opportunistic infections that can cause CNS encephalitis in AIDS patients. This syndrome may be caused by various opportunistic pathogens including Cryptococcus neoformans, Mycobacterium tuberculosis, neuroherpesvirus, and Treponema pallidum.
The focal neurological disease or chagomas should be included in the differential diagnosis of toxoplasmosis, CNS primary lymphoma, tuberculomas, piogenic abscesses due to Nocardia species and Mycobacterium tuberculosis, and finally the progressive multifocal leukoencephalopathy.
Differential diagnosis of myocarditis includes HIV, Toxoplasma gondii, cytomegalovirus, and other herpesvirus.
At this moment, there are only two effective drugs for the treatment of Chagas’ disease: nifurtimox and benznidazole. These two drugs are particularly useful in the acute and early phase of the infection and in the reactivation observed in immunocompromised patients.16,67 Nifurtimox and benznidazole have a greatly limited use related to their frequent and occasionally severe side effects and the necessary long-term treatment.
Other drugs such as allopurinol, ketoconazole, fluconazole, and itraconazole have been used for the reactivation treatment by some authors with apparent success but they are not recommended as first-line therapy.68,69
In consequence, drugs usually used for the therapy of Chagas’ disease in AIDS patients are identical to those that we use in immunocompetent patients. Nifurtimox and benznidazole are the only two drugs effective in killing this parasite in blood and tissues. In the majority of South American countries these drugs are not commercially available for patients in pharmacies. Nifurtimox is unavailable in Argentina and the distribution of Benznidazole depends on the Health Ministry.
The majority of the patients with CNS reactivation of Chagas’ disease associated with AIDS have a poor prognosis and a high mortality related with a delay in the diagnosis and specific therapy. However, the mortality rate diminishes to approximate 20% in patients with at least 30 days of specific treatment.70 Both drugs induce significant side effects and some strains of T. cruzi are resistant to treatment.70
Nifurtimox is a nitrofuran derivate that is used at the dose of 8—10mg/kg per day divided into 2 or 3 doses daily, orally, for 60—90 days. The mechanism of action of nifurtimox involves the production of nitro-anion radicals which, in the presence of oxygen, leave T. cruzi incapable of detoxifying free radicals.71
In countries where nifurtimox is commercialized, the drug has a similar efficacy as benznidazole.
The most frequent adverse side effects observed include anorexia, weight loss, psychological and psychiatric changes (excitability, muscle tremors, somnolence, and hallucinations), and digestive manifestations, such as nausea, vomiting, abdominal pain, and diarrhea. The side effects can be controlled by administrating diazepam, metoclopramide, antihistamines, and other symptomatic medications.
Benznidazole is a nitroimidazole derivate that is administrated orally at the dose of 5 mg/kg per day in two doses for a period of 60 days. The action of benznidazole is related to the introduction of components of the DNA and kDNA of T. cruzi and the lipids and proteins of the parasite.72 Side effects of benznidazole generally occur in the first days of therapy and include cutaneous eruption (including dermatitis, generalized angioedema, and Stevens Johnson syndrome), peripheral neuropathy, and bone marrow depletion (granulocytopenia, thrombocytopenia with purpura). The side effects can be controlled with antihistamines, corticosteroids, and, in severe cases, with the necessary suspension of the treatment (Fig. 30.9).3
After remission of the clinical manifestations, a second prophylaxis is recommended, because further reactivations can occur later. In this aspect, an expert committee recommended the use of benznidazole at the dose of 5 mg/kg per day three times a week up to immune reconstitution associated to antiretroviral therapy (Fig. 30.10).
Highly active antiretroviral therapy should be systematically indicated to these patients in order to achieve the immune reconstitution.66
Primary prophylaxis in chagasic patients infected with HIV is not recommended.
PCR is more sensitive than parasitological tests and could provide earlier evidence of therapeutic failure. Therapeutic efficacy was checked with periodic PCR, hemoculture, and conventional serology.73
Figure 30.9 Therapeutic alternatives for reactivation of Chagas’ disease.
Figure 30.10 Primary and secondary prophylaxis in patients with AIDS and T. cruzi infection.
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