Zoonotic cutaneous leishmaniasis caused by Leishmania major: Do humans play a role in amplifying transmission?

Zoonotic cutaneous leishmaniasis (ZCL) caused by Leishmania (L.) major is the most widespread form of CL worldwide, with hundreds of thousands of cases annually. It is associated with significant morbidity and economic burden, particularly in North Africa and the Middle East. For over a century, the zoonotic transmission of ZCL, involving wild gerbils (Muridae: Gerbillinae) as the reservoir and Phlebotomus (Ph.) papatasi as the vector, has been considered an established fact, with no contradictory debate. However, the pronounced endophilic and anthropophilic behaviors of Ph. papatasi, the exposure of multiple and large lesions, although with relatively limited persistence, to sandflies during their seasonal activity, and the simultaneous detection of human and L. major DNA within the vector, suggest a contribution of humans to the parasite cycle. Conversely, the high incidence of the disease in anthropized foci and the high prevalence of family cases highlight the role of humans in amplifying transmission. The experiments carried out by Adler and Theodor in the 1920s in Palestine and the more recent studies done by Fatemi et al. (2018) in Iran that identified L. major infectious metacyclic forms in Ph. papatasi fed on ZCL lesions reinforce this hypothesis. Additional xenodiagnoses-based approaches could provide definitive answers and lead to better management and control of ZCL, leading to a recommendation of updated preventive measures at the household level. This review aims to report on what is currently known about the zoonotic transmission of L. major, and to develop arguments supporting the hypothesis that humans play a potential role as "reservoir host" of the parasite, albeit a complementary one.