Treatment and resistance in humans
There are various treatment methods depending on the host immune system effectiveness and the type of Leishmania effecting the host as well as the way parasite is transmitted. Host factors such as genetics or immune response or factors related to treatment such as dosage, duration, and completion of the therapy and finally factors related to the parasite, such as intrinsic sensitivity of the species and lack of resistance to the medication are important determinants regarding to treatment of the disease.
Long incubation period of Leishmania parasite makes it a challenge in detection and early treatment methods. If applicable early treatment should be applied in order to further prevent the spreading of the parasite. Having no effective human vaccines puts the disease at a critical point.Pentavalent antimonials, sodium stibogluconate and N-methylglucamine, liposomal amphotericin B, miltefosine, and paramycin are some of the widely used drugs in routine treatment [6, 48]. Compared to liposomal amphotericin B which is a less toxic form, conventional amphotericin B has complicated application procedure and harmful side effects making liposomal amphotericin B a better choice in treatment of both CL and VL which is also an antifungal agent. Still in some underdeveloped or developing countries that cannot afford liposomal amphotericin B treatment, pentavalent antimonials are used. Despite their toxic effects on the liver and kidneys, pentavalent antimonials are still highly effective [49]. On the other hand, emerging resistance limits the therapy frequently. Miltefosine is another drug with known effect of inducing parasite resistance if not used properly.
Global antibiotic resistance problem has emerged in the treatment of leishmaniasis too, and a number of papers reporting treatment failures are increasing [50]. Anthroponotic transmission is the main cause of drug resistance in Leishmania species. Humans being the anthroponotic host, various effects can lead to drug resistance for parasite once treatment starts. Ignoring the recommended consuming amount and frequency of the drug, reduced concentration of the drug effecting the parasite, inhibition of drug activation, inactivation of active drug, and alterations in host gene amplifications are some important example mechanisms for parasites gaining drug resistance. Although, the mechanisms of drug resistance in Leishmania species are not well elucidated in detail, but the involvement of P-glycoprotein (Pgp)-like ABC transporters and ldmdr1 gene has been detected in hard-to-treat parasites [51-54]. In addition, high amount of thiol levels was found to play a role in developing resistance as they prevent reduction of pentavalent antimonials to trivalent antimonials [55].
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