Zinc sulphate in the treatment of cutaneous leishmaniasis: an in vitro and animal study.

This study was designed to evaluate the effectiveness of zinc sulphate both in vitro and in an animal model against both strains of old world cutaneous leishmaniasis. The in vitro sensitivities of promastigotes and axenic amastigotes of both Leishmania major and L. tropica to zinc sulphate was determined, the LD50 calculated and compared to the standard treatment for cutaneous leishmaniasis pentavalent antimony compounds. The results show that the two forms of both strains were sensitive to zinc sulphate and their respective LD50 were lower compared to the pentavalent antimony compound. Furthermore the sensitivities of the forms of both strains were tested using a simple slide method and compared to results of the standard method. To confirm this result, zinc sulphate was administered orally to mice infected with cutaneous leishmaniasis both therapeutically and prophylactically. Results showed that oral zinc sulphate was effective in both treatment and prophylaxis for cutaneous leishmaniasis. These results encourage the use of oral zinc sulphate in the treatment of cutaneous leishmaniasis clinically.

[Metacyclics of Leishmania mexicana in the hypopharynx of Lutzomyia youngi experimentally infected]. / Metaciclicos de Leishmania mexicana en la hipofaringe de Lutzomyia youngi experimentalmente infectada.

Although it has been postulated that the natural transmission of leishmaniasis occurs by regurgitation of the parasites from contaminated proboscis of phlebotomine vector recent experimental results seems to oppose this thesis. Wild-caught and laboratory-reared females of Lutzomyia youngi, vector of Leishmania mexicana in the Venezuelan Andes, were infected on tarsal lesion of hamsters, inoculated 6 weeks previously s.c. with 2 x 10(4) amastigotes of L. mexicana s.l., isolated from Venezuelan case of diffuse leishmaniasis. The insects were kept at 23 degrees C and 80% R.H., on a 50% (v:v) solution of "unrefined" cane sugar. The parasites developed through 3 stages: i) differentiation of the amastigotes and exponential growth in the number of promastigotes, ending between 60 and 108 hrs, with a massive fecal elimination of large promastigotes; ii) a stationary phase in growth with flagellar adhesion to the cuticle of the stomodeum and synthesis of a gel that formed a plug between 60 and 120 hrs; iii) differentiation of metacyclics, which invade the hypopharyngeal duct in 7% of the insects, from the 5th day post-infection, and most frequently between the 6th and 9th day. The metacyclics measured 4.2/microns in body length, 1.07/microns in maximum with and the flagellum was 8.8/microns long. The parasites swam freely in the saliva of the hypopharyngeal duct (lumen 6/microns in diameter), from the apex to union with the salivary duct, without invading the latter. Similar results has been obtained in the same vector experimentally infected with other two strains of L. mexicana isolated respectively from wild Lu. flaviscutellata and from another case of diffuse leishmaniasis.(ABSTRACT TRUNCATED AT 250 WORDS)

Biochemical characteristics of the metacyclic forms of Leishmania major and L. mexicana mexicana.

Metacyclic forms of Leishmania major and putative metacyclics of L. mexicana mexicana were found to occur in abundance in stationary phase cultures. These forms have been compared in several ways with promastigotes from mid-log phase cultures and, in the case of L. m. mexicana, amastigotes. Metacyclics are smaller, contain less protein and appear more active than other promastigotes. Both forms of promastigote respire at a high rate in the absence of exogenous substrate. The free amino-acid contents of the various forms of the two species have been analysed. They differ in detail but alanine was the major amino acid in all cases. The isoenzyme content of the different forms differed significantly. That of the putative metacyclics of L. m. mexicana was in several respects more similar to amastigotes than promastigotes, suggesting that the form is pre-adapted for life in a mammal. Metacyclics of L. major apparently did not divide in culture but transformed back over a period of 48 h to mid-log phase cells. The results provide further detail of the molecular differences between mid-log phase and metacyclic promastigotes and confirm that metacyclics are a distinct form in the life-cycle.

Sex differences and cross-immunity in DBA/2 mice infected with L. mexicana and L. major.

Female DBA/2 mice were found to be highly resistant to Leishmania mexicana and rarely developed lesions even when inoculated subcutaneously with high numbers (5 x 10(6] of amastigotes. Male DBA/2 mice, on the other hand, were much more susceptible to this parasite and often developed non-healing lesions even when inoculated subcutaneously with comparatively few (5 X 10(4] amastigotes. Conversely, although both male and female DBA/2 mice developed ulcerating lesions when inoculated subcutaneously with L. major amastigotes, lesions invariably healed in males but did not heal in females. Male DBA/2 mice recovered from L. major infection subsequently were found to be resistant to subcutaneous challenge with L. mexicana. Conversely female DBA/2 mice that had failed to develop lesions when infected with L. mexicana developed lesions which healed following subcutaneous challenge with L. major. Thus there is bilateral cross-immunity between L. mexicana and L. major in DBA/2 mice which overrides differences in sex-determined susceptibility to both organisms.