Tackling Drug Resistance and Other Causes of Treatment Failure in Leishmaniasis

Abstract

Leishmaniasis is a tropical infectious disease caused by the protozoan Leishmania parasite. The disease is transmitted by female sand flies and, depending on the infecting parasite species, causes either cutaneous (stigmatizing skin lesions), mucocutaneous (destruction of mucous membranes of nose, mouth and throat) or visceral disease (a potentially fatal infection of liver, spleen and bone marrow). Although more than 1 million new cases occur annually, chemotherapeutic options are limited and their efficacy is jeopardized by increasing treatment failure rates and growing drug resistance. To delay the emergence of resistance to existing and new drugs, elucidating the currently unknown causes of variable drug efficacy (related to parasite susceptibility, host immunity and drug pharmacokinetics) and improved use of genotypic and phenotypic tools to define, measure and monitor resistance in the field are critical. This review highlights recent progress in our understanding of drug action and resistance in Leishmania, ongoing challenges (including setbacks related to the COVID-19 pandemic) and provides an overview of possible strategies to tackle this public health challenge.

Host, parasite and drug determinants of clinical outcomes following treatment of visceral leishmaniasis: a protocol for individual participant data meta-analysis

“…Similarly, the exploration of parasitic factors is limited to parasite gradation and the nature of the infection (primary vs previously treated cases). Other important parasite factors such as in vitro status of drug susceptibility, their virulence and the underlying genomic plasticity allowing parasites to undergo mutation under drug pressure49 50 are not routinely collected in clinical trials and hence remains beyond the scope of this IPD-MA.…”

Neglected Zoonotic Diseases: Advances in the Development of Cell-Penetrating and Antimicrobial Peptides against Leishmaniosis and Chagas

“…Nowadays, there is global alarm concerning the development of multidrug resistance by microorganisms, and this has also been identified in Leishmania [72] and Chagas disease infections [73]. AMPs and CPPs have multiple mechanisms of action, making it difficult for pathogens to develop resistance [74].…”

Synthesis and Evaluation of (Bis)benzyltetrahydroisoquinoline Alkaloids as Antiparasitic Agents

“…The fatality of the disease is attributed to the parasite spreading to and irreversibly damaging vital organs such as the liver, spleen, and bone marrow . First line treatments are limited to pentavalent antimonials, liposomal amphotericin B, and miltefosine. − However, all drugs currently in use suffer from drawbacks such as long and expensive treatment courses and associated toxicity. , The related protozoan Trypanosoma cruzi causes Chagas disease, which affects over 8 million people, predominantly in South America . Similarly to leishmaniasis, this disease can be difficult to diagnose due to asymptomatic patients that become chronically infected in the absence of treatment .…”