leishmaniasis
Leishmaniasis is one of the neglected tropical, vector-borne diseases which is widely spread in tropical and certain subtropical areas[38], [39]. The poorest people with malnutrition, population displacement, weak immune system, poor housing, and lack of financial resources are affected more by this disease. According to the world health organization, around 700 000 to 1 million new cases occur annually. Leishmaniasis is caused by an intracellular flagellated Trypanosomatid protozoan parasite that belongs to the genusLeishmania [40], [41]. These parasites are transmitted by infected phlebotomine female sand fly bites[40]. Around 20 Leishmania species are identified as pathogenic to humans which are transmitted by around 30 species of phlebotomine sandflies[40], [41]. Leishmania parasites have a digenetic lifecycle where they spend the flagellated promastigote form inside the sand fly which is the vector, and the non-flagellated amastigote form inside the mammalian host[42], [43]. Inside the mammalian host, Leishmania mainly infects host macrophages[44]. Upon entering into macrophages, to ensure its stabilization and survival against macrophage’s defense responses such as immune activation, oxidative stress, and apoptosis, theLeishmania parasite modulates the host macrophage in such a way that it can overcome the host immune response against the infection[8], [13], [44].
Leishmaniasis is clinically classified into three forms, namely; cutaneous leishmaniasis (CL), visceral leishmaniasis (VL), and mucocutaneous leishmaniasis (MCL) which is caused by the replication of the infected parasite in macrophages in the dermis, reticuloendothelial system, dermis, and naso-oropharyngeal mucosa, respectively [40], [41], [45]. When the macrophage is full of parasites within its hold, the host cell bursts and releases the parasites that will go and infect the neighboring macrophages[40]. Untreated VL can cause life-threatening systemic infection while CL can cause chronic skin sores. Facial disfigurement and life-threatening destruction of nasopharyngeal mucosa can be caused by the MCL[46]. Multiple species of the genus Leishmania cause CL: L. tropica, L. major, L. aethiopica, L. infantum, and L. donovani in the old world (Africa, Asia, and Europe), and L. mexicana, L. amazonensis and L. braziliensis in the new world [41], [46]. Moreover, many intracellular pathogens like Leishmania can interact and hijack cellular organelles like endoplasmic reticulum (ER) for their survival and replication, triggering the ER stress and subsequently ER stress response [7], [8]