Introduction
Leishmaniasis is an infectious disease caused by several different species of protozoan parasites of the genus Leishmania. Current strategies to control this disease are mainly based on chemotherapy. Leishmanial chemotherapy has lack of efficiency, since its route of administration is difficult and it can cause serious side effects, which results in the emergence of resistant cases. The medical-scientific community is facing difficulties to overcome these problems with new suitable and efficient drugs, as well as the identification of new drug targets.
Recently, few alternative drugs have emerged for the treatment of leishmaniasis. None of the available drugs can be considered ideal due to their high toxicity, long duration of treatment, and severe adverse reactions, which lead to treatment abandonment. In addition, the most commonly used drugs do not eliminate the parasites completely from all infected individuals.
Pentavalent antimonials
The most frequently used drugs for the treatment of leishmaniasis, despite their variable effectiveness for both visceral and cutaneous leishmaniasis.
Side Effects
Due to accumulation in the tissues, antimonials can cause serious adverse effects, such as vomiting, nausea, anorexia, myalgia, abdominal pain, headache, arthralgia, and lethargy and can rarely cause the severe reaction of fatal cardiac arrhythmia.
Amphotericin B
Despite its high toxicity, amphotericin B is one of the first-line drugs for leishmaniasis treatment. Its intravenous administration frequently causes rigor, chills and fever, associated with myocarditis and nephrotoxicity. Amphotericin B formulations (the lipid complex, colloidal form, and the liposomal form) were developed to reduce adverse effects and improve pharmacokinetics and bioavailability.
Pentamidine
This is another drug currently used for treatment of leishmaniasis. It is highly toxic and triggers important adverse effects, such as diabetes mellitus, severe hypoglycemia, hypotension, myocarditis, and renal toxicity and can ultimately cause death. This drug is currently used infrequently due to the appearance of resistance cases, its high toxicity, and low efficacy. Currently, pentamidine is mainly recommended when used in combined therapeutic protocols.
Adults and children doses for leishmaniasis are 2 – 3 mg/kg IN or IV once a day or every second day for 4 – 7 doses.
Paromomycin
This is an alternative drug for leishmaniasis treatment. However, parenteral formulations can cause serious adverse reactions, including nephrotoxicity and ototoxicity and more rarely hepatotoxicity.
Mitelfosine
Mitelfosine is an alternative antileishmanial drug which has the advantage of oral administration. However, its use is limited for pregnant women, since the most severe side effects of this drug are the induction of teratogenesis and the occurrence of a high index of treatment failure.
Regarding selective antileishmanial activity, pentavalent antimonials can act against different species of Leishmania, whereas pentamidine has limited activity against specific Leishmania species. Paromomycin can be used topically to treat localized leishmaniasis caused by L. braziliensis, but not for that caused by other species of Leishmania. Miltefosine, which is effective for the treatment of visceral leishmaniasis caused by L. donovani, seems to be ineffective in the treatment of infection by L. major and L. braziliensis.
Rational combination of drugs, have favorably reduced individual doses, treatment duration, and adverse effects there by reducing costs, the frequency of treatment failure, and the occurrence of drug resistance.