Field effectiveness of new visceral leishmaniasis regimens after 1 year following treatment within public health facilities in Bihar, India

Background An earlier open label, prospective, non-randomized, non-comparative, multi-centric study conducted within public health facilities in Bihar, India (CTRI/2012/08/002891) measured the field effectiveness of three new treatment regimens for visceral leishmaniasis (VL): single dose AmBisome (SDA), and combination therapies of AmBisome and miltefosine (AmB+Milt) and miltefosine and paromomycin (Milt+PM) up to 6 months follow-up. The National Vector Borne Disease Control Program (NVBDCP) recommended an extended follow up at 12 months post-treatment of the original study cohort to quantify late relapses. Methods The 1,761 patients enrolled in the original study with the three new regimens were contacted and traced between 10 and 36 months following completion of treatment to determine their health status and any occurrence of VL relapse. Results Of 1,761 patients enrolled in the original study, 1,368 were traced at the extended follow-up visit: 711 (80.5%), 295 (83.2%) and 362 (71.5%) patients treated with SDA, AmB+Milt and Milt+PM respectively. Of those traced, a total of 75 patients were reported to have relapsed by the extended follow-up; 45 (6.3%) in the SDA, 25 (8.5%) in the AmB+Milt and 5 (1.4%) in the Milt+PM arms. Of the 75 relapse cases, 55 had already been identified in the 6-months follow-up and 20 were identified as new cases of relapse at extended follow-up; 7 in the SDA, 10 in the AmB+Milt and 3 in the Milt+PM arms. Conclusion Extending follow-up beyond the standard 6 months identified additional relapses, suggesting that 12-month sentinel follow-up may be useful as a programmatic tool to better identify and quantify relapses. With limited drug options, there remains an urgent need to develop effective new chemical entities (NCEs) for VL.
Author summary In 2010, the WHO Expert Committee recommended liposomal amphotericin B (in single or multiple doses) along with three short combination treatment regimens containing liposomal amphotericin B (LAmB), miltefosine (Milt) and/or paromomycin (PM) as preferred options to replace the existing miltefosine monotherapy for kala-azar treatment in South Asia. The Drugs for Neglected Diseases initiative (DNDi) in partnership with Rajendra Memorial Research Institute of Medical Science (RMRI-Regional ICMR institute), State Health Society Bihar, and Médecins Sans Frontières (MSF) conducted a phase 4 field effectiveness study to determine the effectiveness and to assess the safety and feasibility of using single dose LAmB, and the combination therapies of LAmB+Milt and Milt+PM for the treatment of VL at public healthcare facility settings in India. Based on the provisional results of this effectiveness study at 6 months follow-up, the Indian government revised the national policy in August 2014, introducing SDA as first option and Milt+PM as second option to replace miltefosine monotherapy in the kala-azar elimination initiative. National Vector Borne Disease Control Programme (NVBDCP) expert committee recommended to follow up this large cohort of patients for one year to identify relapses yielding further evidence on new treatment regimens.