Efficacy and Safety outcomes: Liposomal Amphotericin B Ambisome treatment for Visceral Leishmaniasis VL under routine pr

1. Efficacy and Safety outcomes: Liposomal Amphotericin B (Ambisome) treatment for Visceral Leishmaniasis (VL) under routine programme conditions in Bihar, India. Jitendra Gupta MSF- Spain

2. Facts about VL A major neglected disease. Worldwide around 500,000 new cases/ year. Only 5 countries have more than 90% of cases (India, Bangladesh, Nepal, Sudan and Brazil). Leishmania donovani, Kala-Azar in Indian subcontinent. Fever, weight loss and enlarged spleen. If untreated, anemia and wasting, fatal illnesses in 95% of cases.

4. Bihar background Second poorest state of the country. Around 60 � 75% VL cases of India are in Bihar alone.

5. Available Treatment Options Sodium Stibogluconate (SSG) Pentamidine Isethionate Paromomysin (also called Aminosidine) Miltefosine Amphotericin B Liposomal Amphotericin B

6. Liposomal Amphotericin B (Ambisome) Safest available drug for VL treatment. First line treatment for VL in resource rich settings. Phase II studies showed: High efficacy (89-100%). Low safety risk. No phase III or IV study data available. High cost of the drug. Treatment cost: 50 mg vial cost 20 USD. 40 kg patient need 20 vials (40x 20= 800/50 = 16 vials) 16x20= 320 USDTreatment cost: 50 mg vial cost 20 USD. 40 kg patient need 20 vials (40x 20= 800/50 = 16 vials) 16x20= 320 USD

7. MSF-Spain VL project in Bihar

8. Objectives To evaluate effectiveness of first line AmBisome, at a total dose of 20mg/kg body weight. To evaluate tolerability and safety of first line AmBisome treatment, at above dosage, under routine programme conditions.

9. Methodology Prospectively monitored and evaluated a cohort of VL patients. Ambisome 20 mg/kg body weight on day 0, 1, 4 & 9 (WHO recommended, 2005). Inclusion: The first 250 patients diagnosed with primary VL. Clinically & Rk 39 dipsticks positive. Exclusion: Patients previously treated with Ambisome. Patients with relapse, <2 years, HIV or TB co-infected.

10. Continued� Safety monitoring: Clinical assessment Hemoglobin, Weight End points: At the end of treatment (day 10). 3-months after the treatment. Final cure at 6-months. Clinically well If clinically suspected, parasitological clearance

11. Characteristics on Admission: ? 15 years N (%) = 128 (51%), Secondary infections Total: 92 (37%) ? 15 years N (%) = 128 (51%), Secondary infections Total: 92 (37%)

12. Main Adverse Events

13. Outcomes

14. Clinical Markers for Improvement

15. Odds Ratio (Intention to Treat)

16. Conclusion Ambisome (20 mg/kg bw) shows high effectiveness (96%), under routine programme conditions. Extremely safe: only 0.23 adverse event per treatment. High tolerability.

17. Key Issues & Recommendations High drug cost. New implementation programmes with Ambisome 15 mg and closely monitored under field conditions should be undertaken. Further combination studies with Ambisome as the main drug, to be combined with other drugs, should be urgently explored. *Some phase II studies with low dosage (15mg/kg bw), showed good efficacy and safety profile. *Some phase II studies with low dosage (15mg/kg bw), showed good efficacy and safety profile.

18. Acknowledgements Thank you!! MSF Spain MSF Spain, India, Hajipur RMRI, Patna Manica Balasgaram