High Inoculum Doses of <i>Leishmania mexicana</i> Induce Severe Diffuse Cutaneous Leishmaniasis in Susceptible Mice

<i><b>Background:</b> Leishmania mexicana</i> was identified as the causal agent of localized as well as diffuse cutaneous leishmaniasis (DCL) in Mexico. <b><i>Methods:</i></b> To clarify the roles of the inoculum size and host sex, three different doses of the <i>L. mexicana</i> reference strain MNYC/BZ/62/M379 were inoculated into susceptible BALB/c mice. <b><i>Results:</i></b> A low dose (25 × 10⁰) did not produce lesions, a medium dose (25 × 10³) produced localized lesions, and a high dose (25 × 10⁶) 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 <i>L. mexicana</i> isolates obtained from patients with either localized or diffuse forms of the disease. <b><i>Conclusion:</i></b> We concluded that DCL caused by <i>L. mexicana</i> is a severe form of tegumentary leishmaniasis caused by a high parasite inoculum dose in susceptible hosts, with increased susceptibility in males.