Twelve Months Outcome In Kala-Azar Patients Treated With 3 Novel Regimens, At Public Health Care Facilities In Bihar

Background: Kala-azar elimination initiative launched in 2005 in South Asia aims to reach the target by 2017. Early diagnosis and effective treatment is one of the key strategies for control along with integrated vector management. Single dose Ambisome (SDA) and combination regimens are the recommended treatments in South Asia. Our objective was to assess feasibility of using these treatments within the public health facilities and document 12 month outcome. Methods & Materials: This was an open label, prospective, non-randomised, non-comparative, multicentric trial conducted at public health facilities. The study was conducted from Aug 2012 to Sep 2015 at 02 districts (Vaishali and Saran) in Bihar and at kala-azar referral hospital (Rajendra Memorial Research Institute of Medical Sciences) in Patna. In Vaishali district, patients were treated with SDA (10mg/kg) at the District hospital and A+M (single dose Ambisome 5mg/kg + miltefosine 7 days) at 5 primary healthcare centres (PHC). In Saran District, M+P (Miltefosine and Paromomycin) for 10 days at district hospital and 3 PHC. All patients were followed up to document outcome at 6 months and cohort of them were followed for 12 months. Results: 1761 patients were treated in the study, achieved cure rate of > 99% at initial outcome (Day 10) in each treatment arm. The cure rates at 6 months were 90.9% (95% CI 89.0-92.8) for SDA (n=892), 88.8% (CI 85.5-92.1) for A+M (n=357) and 97.0% (CI 95.6-98.5) for M+P arm (n=512). During 12 month FU (n=1386) there were 11 additional relapses, 2 in SDA (n=706) and 6 in A+M (n=294) and 3 in M+P (n=386). 12 patients developed PKDL in M+P arm, 1 in A+M arm and 2 in SDA. Five SAE occurred in SDA arm, 2 considered related and 3 non-related to Ambisome, all of them resolved. Conclusion: The new treatment regimens showed excellent outcome and safety profile to be used within the programme settings. On the basis of these results, Indian national program have revised the treatment policy in Sep 2014 where SDA has been recommended as the 1st option and M+P as the 2nd option. Extension of FU beyond the standard 6 months yielded additional relapses and PKDL cases.