Combination therapy for visceral leishmaniasis

Abstract

Drugs for visceral leishmaniasis (also known as kala-azar) have several drawbacks, such as long regimen duration, parenteral administration, toxic effects, or high costs. 1 Alvar J Croft S Olliaro P Chemotherapy in the treatment and control of leishmaniasis. Adv Parasitol. 2006; 61: 223-274 Crossref PubMed Scopus (204) Google Scholar Furthermore, drug resistance against antimonials is widespread in India, and could also emerge in new drugs. 2 Bryceson A A policy for leishmaniasis with respect to the prevention and control of drug resistance. Trop Med Int Health. 2001; 6: 928-934 Crossref PubMed Scopus (146) Google Scholar , 3 Croft SL Sundar S Fairlamb AH Drug resistance in leishmaniasis. Clin Microbiol Rev. 2006; 19: 111-126 Crossref PubMed Scopus (1274) Google Scholar Combination therapy could be the way forward: a shorter regimen might be more affordable, easier to administer, and better adhered to than are current, longer regimens, and might protect the lifespan of the individual drugs. 4 Van Griensven J Balasegaram M Meheus F Alvar J Lynen L Boelaert M Combination therapy for visceral leishmaniasis. Lancet Infect Dis. 2010; 10: 184-194 Summary Full Text Full Text PDF PubMed Scopus (242) Google Scholar In The Lancet, Shyam Sundar and colleagues 5 Sundar S Sinha PK Rai M et al. Comparison of short-course multidrug treatment with standard therapy for visceral leishmaniasis in India: an open-label, non-inferiority, randomised controlled trial. Lancet. 2011; (published online Jan 20.)https://doi.org/10.1016/S0140-6736(10)62050-8 Summary Full Text Full Text PDF Scopus (253) Google Scholar report a phase 3 non-inferiority trial in India, in which they compared three drug combinations (10 days each of paromomycin and miltefosine; single-dose liposomal amphotericin B and 10-day paromomycin; and single-dose liposomal amphotericin B and 7-day miltefosine) with the standard treatment for visceral leishmaniasis (conventional amphotericin B). All three combinations were efficacious and well tolerated with 6-month definitive cure rates of at least 97%. Regimen duration ranged from 8 to 11 days—shorter than the 21–28 days for current monotherapies. These data are very encouraging and further support the rationale of combination therapy for visceral leishmaniasis because they provide several safe and efficacious options. However, several issues still need to be addressed. Comparison of short-course multidrug treatment with standard therapy for visceral leishmaniasis in India: an open-label, non-inferiority, randomised controlled trialCombination treatments for visceral leishmaniasis are efficacious and safe, and decrease the duration of therapy, thereby encouraging adherence and reducing emergence of drug-resistant parasites. Full-Text PDF