Improving methods for epidemiological control of canine visceral leishmaniasis based on a mathematical model: impact on the incidence of the canine and human disease

O modelo matemático descrito por Dye (1996) condenava a campanha de controle do calazar canino por considerá-la ineficaz. Usando esse modelo, demonstramos matematicamente que a ineficácia somente ocorre com valores baixos de k (índice de remoção de cães infecciosos pela campanha de controle), que coincide com os valores de soropositividade detectados no campo, pelo método de imunofluorescência (IF) em eluatos. Aplicando valores maiores de k, o controle se tornaria eficaz: valores de k correspondentes a IF (k = 0.07) ou ELISA em soros (k = 0.25) diminuiriam o numero de cães infecciosos, levando o valor de Ro a 1 ou 0 respectivamente, impedindo com isso a transmissão e o avanço da epidemia. Demonstramos experimentalmente que a remoção de cães conforme os resultados de IF nos soros em lugar de eluatos diminuiu 57% dos casos caninos (p < 0.005) e de 87.5% dos casos humanos (p < 0.005). Os nossos resultados, demonstram que a campanha de controle se torna eficaz aumentando a sensibilidade do método diagnóstico.

The FML vaccine (fucose-mannose ligand) protects hamsters from experimental kala-azar

Visceral leishmaniais or kala-azar, is a chronic and frequently lethal disease, caused by Leishmania donovani. Clinical signs include malaise, hepatosplenomegaly, hypergammaglobulinemia, fever, cachexia and progressive suppresion of the cellular immune response. Only few studies on prophylactic immunization against this disease have been understaken, mostly with crude antigens, and no vaccine against kala-azar is yet available. In previous studies, we have isolated the Fucose-Mannose Ligand (FML) of L. donovani that strongly and specifically inhibits the in vitro infection of macrophages by promastigotes and amastigotes. The FML behaves as a pontent immunogen for rabbits and mice, and is specifically recognized by kala-azar patient sera. The protective pontential of FML on kala-azar was now analyzed in the CB-hamster model. We studied the efect of three intraperitoneal weekly doses of FML (100 mg) in saponin (100 mg), folowed by an intracardiac injection of 107 amastigotes. Saponin- and saline-treated controls were also included. Protection was highly significant regarding the enhancement of anti-FML antibodies titers, the splenocyte proliferative response, and the intradermal delayed hypersensitivity reaction to antigen, as well as the decrease of the parasite burden in spleen and of splenomegaly. Protection to kala-azar was due to specific FML antigenic properties, since the results obtained by saponin alone were significantly different. We conclude that the use of FML and saponin as a vaccine reduced the disease impact and retarded its onset.