Zoonotic cutaneous leishmaniasis (ZCL), caused by Leishmania major, is a neglected tropical disease affecting impoverished populations. Current treatments are limited by cost, resistance, and side effects, highlighting the need for affordable, sustainable interventions. Lucilia sericata larvae, used in maggot therapy, effectively treat chronic wounds through debridement, antimicrobial activity, and healing promotion. This study explores how L. sericata processes L. major and proposes its potential application in ZCL treatment. The life cycles of L. sericata and L. major were maintained in laboratory conditions. Larval-parasite interactions were tested across substrates [hen liver, rat spleen, Roswell Park Memorial Institute (RPMI) 1640 cell culture medium] and time intervals (30-240 minutes). Extracorporeal effects were evaluated using trypan blue exclusion and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays; intracorporeal interactions via microscopy and nested-PCR targeting L. major rRNA genes. L. sericata excretion/secretion products and microbiota exhibited strong anti-leishmanial activity. Promastigotes were deformed within 1 hour post-exposure (hpe), fully inactivated at 4 hpe, and lysed by 6 hpe. In RPMI medium, the treatment group (L. sericata + L. major) showed significant reductions in active parasites and viable cells compared to controls after 4 hours. Microscopy revealed no parasites in larval guts, but PCR detected L. major DNA in all specimens, suggesting partial digestion. This study demonstrates that L. sericata can eliminate L. major through intra- and extra-oral digestion, supporting its potential as a biotherapeutic agent for ZCL-associated wounds. These findings offer a foundation for developing larval therapy protocols in dermatology. Further studies in animal models and clinical trials are required to validate this approach for managing ZCL.
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