Leishmaniasis is a Neglected Tropical Disease caused by protozoan parasites from the genus Leishmania. It is transmitted by the bite of infected female sand flies. There are three main forms of leishmaniasis- visceral leishmaniasis (VL), also known as kala-azar, cutaneous leishmaniasis (CL) and mucocutaneous leishmaniasis (MCL). Leishmaniasis affects some of the world’s poorest people and is present in 98 countries across the world. An estimated 700,000 to 1 million new cases occur annually. If left untreated, leishmaniasis can develop into a chronic disease and cause severe damage to internal organs and eventual death.
Types of Leishmaniasis
Visceral Leishmaniasis is the most severe form that affects internal organs like the spleen, liver, and bone marrow. Some common symptoms of VL include fever, weight loss, swelling of the spleen and liver, and anemia. It is usually fatal if left untreated. Cutaneous leishmaniasis causes sores or ulcers on exposed parts of the body like the hands, legs and face. Mucocutaneous leishmaniasis is the most serious form which can destroy skin and mucosal tissues of the nose, mouth and throat. Untreated MCL may ultimately lead to destruction of mucosa and cause gross disfigurement of face.
Drugs for Visceral Leishmaniasis Treatment
The first line treatment recommended by the World Health Organization for VL is a combination of sodium stibogluconate (SSG) and paromomycin given intramuscularly. SSG requires painful daily injections over a period of 20-30 days. Paromomycin needs to be given for 15-21 days. This combination gives cure rates over 95%. However, both drugs cause significant side effects like pain at the injection site and fever. For patients not responding to the first line treatment, Amphotericin B liposomal is given which has fewer side effects. Other second line drugs include miltefosine and combination therapies using molecules like liposomal amphotericin.
Treatment for Cutaneous Leishmaniasis
Most cases of CL can be treated with topical agents applied directly onto the skin lesions. Options include paromomycin, methylbenzethonium chloride and thermotherapy using heat. Oral medications like Pentostam, miltefosine and fluconazole are also effective against CL. Relatively uncomplicated CL cases usually heal with scarring within 2–3 months of treatment. However treatment may need to be continued for 4–6 weeks or longer for extensive, recurrent or non-responsive lesions. Severe or non-responsive CL may require systemic drugs like pentamidine, amphotericin B or miltefosine given parenterally or orally.
Drug Resistance in Leishmania
Emergence of drug resistance in Leishmania parasites is a growing public health problem. Resistance to standard anti-leishmanial drugs has been reported from many endemic countries. The factors responsible for development of resistance include sub-therapeutic drug levels due to suboptimal dosing regimen, irregular supplies of medications, genetic diversity in different Leishmania species and strains. Multi-drug resistance has been observed to both pentavalent antimonials (the first line treatment since 1930s) as well as pentamidine, amphotericin B and paromomycin. This has led to increasing treatment failure rates and failures of both first and second line drugs. Monitoring drug resistance is crucial for timely implementation of alternative treatment options.
Newer Treatment Approaches
Various new anti-leishmanial molecules are being evaluated for safety, efficacy and as alternatives to existing drugs to which resistance has emerged. These include oral agents like sitamaquine, azoles, oxaboroles and aminoglycosides conjugates, as well as formulations like liposomal amphotericin. Monoclonal antibody therapies are also being explored against leishmaniasis. Vaccines are being developed and tested to offer protective immunity. Novel drug delivery systems using nanotechnology and implants/patches are being developed for targeted and prolonged drug release. Combination therapies, rational drug combinations as well as chemosensitizers hold promise to improve treatment outcomes and check development of resistance. Immunotherapy along with chemotherapy also shows good potential.
Leishmaniasis remains a Neglected Tropical Disease profoundly affecting poor communities worldwide. Though several treatment options exist in principle, availability, access and emergence of resistance to drugs underline an urgent need for newer, affordable and effective anti-leishmanial therapies. Addressing drug resistance and introducing alternative strategies will be central to achieving treatment success sustainably. Increasing investments in research on Leishmania biology and pathogenesis, drug discovery and accelerated clinical trials has potential to combat this debilitating yet curable disease. Public health interventions for vector control coupled with medical interventions can help eliminate leishmaniasis in near future.
