High Inoculum Doses of Leishmania mexicana Induce Severe Diffuse Cutaneous Leishmaniasis in Susceptible Mice

Background: Leishmania mexicana was identified as the causal agent of localized as well as diffuse cutaneous leishmaniasis (DCL) in Mexico. Methods: To clarify the roles of the inoculum size and host sex, three different doses of the L. mexicana reference strain MNYC/BZ/62/M379 were inoculated into susceptible BALB/c mice. Results: A low dose (25 × 10 0 ) did not produce lesions, a medium dose (25 × 10 3 ) produced localized lesions, and a high dose (25 × 10 6 ) produced diffuse leishmaniasis. Male mice became infected with the reference strain M379 at a dose 1000 times lower than that required to produce the same type of infection in female mice. Male mice developed lesions 2 or 3 months earlier than female. The dose-dependent severity of lesions was confirmed in 22 previously frozen L. mexicana isolates obtained from patients with either localized or diffuse forms of the disease. Conclusion: We concluded that DCL caused by L. mexicana is a severe form of tegumentary leishmaniasis caused by a high parasite inoculum dose in susceptible hosts, with increased susceptibility in males.