Is leishmaniasis ever cured?

The persistence of parasites in mice cured of Leishmania mexicana infection was investigated by using immunosuppressive drugs and checking for the reappearance of lesions. BALB/c (susceptible) and C57BL/6 (partially resistant) mice infected with 10(4) amastigotes were treated with either thermotherapy or meglumine antimonate and subsequently immunosuppressed with either cyclophosphamide or hydrocortisone. Immunosuppression by either method caused lesions to reappear in both strains of mice regardless of the treatment used to produce clinical cure. In both strains of mice the proportion of animals developing lesions after immunosuppression was greater in the mice cured by the drug. The relevance of these findings to human therapy is discussed.

Cardiac parasympathetic innervation in Chagas' heart disease.

Trypanosoma cruzi is thought to selectively destroy the postganglionic cardiac vagal neurons of chagasic cardiac patients. This theory is based on morphologic and functional evidences obtained from chagasic individuals who were in very advanced stages of the disease. We have studied chagasic patients who were in both the early and late stages of the disease. Our findings and the review of the available literature suggest that myocardial damage and mild left ventricular dilatation precede the cardiac parasympathetic abnormalities. Furthermore, we have found a strong correlation between the degree of left ventricular dilatation and the extent of cardiac parasympathetic impairment. Consequently, we propose that the cardiac parasympathetic abnormalities arise as a compensating mechanism for the progressive left ventricular dilatation.

Cardiac autonomic control mechanisms in Chagas' heart disease. Therapeutic implications.

According to the neurogenic theory of Chagas' heart disease, the cardiac parasympathetic abnormalities of chagasic cardiac patients are due to a selective destruction of the cardiac parasympathetic neurons. Trypanosoma cruzi would selectively destroy the cardiac vagal neurons, during the acute stage of the disease. However, these cardiac parasympathetic abnormalities are found mainly in chagasic patients who are in very advanced stages of the disease. Furthermore, the extent of cardiac parasympathetic involvement correlates with the degree of left ventricular dilation. Cardiac parasympathetic abnormalities, and a reciprocal sympathetic hyperactivity are also present in non-chagasic cardiac patients. Modern medical treatment, with sympatholytic drugs, prevents ventricular dilatation and prolongs life in these non-chagasic cardiac patients. Consequently, if chagasic cardiac patients have ventricular dilatation-related parasympathetic abnormalities; it is of the utmost importance to ask: first, do they also have a progressive activation of their neurohumoral systems?; and second, would they benefit from sympatholytic drugs?.

Thermotherapy v. antimonials: what happens after the healing of cutaneous leishmaniasis lesions?

The long-term effects of meglumine antimoniate (chemotherapy) or exposure to an environmental temperature of 37 degrees C (thermotherapy) on the evolution of Leishmania mexicana infections and on the response to challenge infections six months after treatment were compared in susceptible (BALB/c) and partially resistant (C57BL/6) mice. Thermotherapy was better than chemotherapy in that it healed lesions quicker and prevented relapses in the partially resistant mice during the observation period. However, both treatments appeared equally effective in terms of clinical cure. Neither treatment cleared all parasites from the hosts and both impaired the hosts' immune response to a challenge infection. The results indicate that specific immunity fades with time post-infection and that the persistence of the parasite in a clinically cured host does not maintain protective immunity against challenge infections.

Intralesional isotype profiles in human localized cutaneous leishmaniasis lesions.

This immunocytochemical study evaluates the presence of IgG1-4, IgA and IgE immunoglobulins in active lesions of 25 localized cutaneous leishmaniasis patients from three bioclimatic areas (Awa, Afa and Bsha) in Mérida State, Venezuela. All immunoglobulin isotypes except IgE were detected, with variable intensity, in one or more of the epidermal or dermal components of skin lesions. IgG1 and IgG2 were detected significantly more frequently than IgG3, IgG4 and IgA. The ranking of the isotypes according to frequency of detection was the same in all areas: IgG1 = IgG2 > IgG3 = IgG4 = IgA, but considered as whole, all isotypes were detected significantly more frequently in patients from the Awa area than in those from the Bsha area. The predominant expression of isotypes IgG1 and IgG2 suggests a preferential Th1 like immune response. Anti-Leishmania immunoserum stained only parasites and their debris, suggesting that most of the immunostaining was nonspecific.