1. Post kala-azar dermal leishmaniasis treated with liposomal amphotericin B
MSF OCA, OCBA
Bangladesh, India
*Sakib Burza1,2, Margriet den Boer5, Raman Mahajan1, Temmy Sunyoto1, Marıa Angeles Lima3, Asish Kumar Das4, Patrick Almeida4, Gaurab Mitra1, A. Be-Nazir6, Pradeep Das7, Koert Ritjmeijer5
1Médecins Sans Frontières (MSF), New Delhi, India; 2Institute of Tropical Medicine, Antwerp, Belgium: 3MSF, Barcelona, Spain; 4MSF, Dhaka, Bangaldesh; 5MSF, Amsterdam, Holland: 6Communicable Disease Control, Ministry of Health and Family Welfare, Dhaka, Bangladesh, 7Rajendra Mamorial Research Institute, Patna, India

2. Post Kala Azar Dermal Leishmaniasis (PKDL)
Is a complication of visceral leishmaniasis
Common in areas endemic for VL caused by L.donovani
Characterised by a skin rash after an episode of VL
In contrast to VL:
Patients are typically not ill
PKDL is not fatal
Main issue is that of aesthetics
However, is a public health problem:
Based on existing evidence, PKDL is a major reservoir of L.donovani
In South Asia, PKDL does not self heal
Needs to be treated if transmission of disease is to be limited
Estimated 5-10% of VL cases go on to develop PKDL
Incidence 4.8/1000, interval 0-3 years post initial VL infection

3. A neglected disease within a neglected disease
Very poor evidence base and understanding of PKDL as a disease process
Limited evidence on pathogenesis or risk factors
Accurate diagnosis is difficult, needs experience and skilled HR
Serological diagnosis difficult to interpret
Very little evidence on management:
No evidence on ‘skin penetration’ of existing drugs
No evidence on ‘end point’ of treatment
Very limited evidence on treatments

4. Examples of PKDL morphologies:

5. Existing evidence for treatment of PKDL
In South Asia, only one RCT to date
Compared miltefosine (MF) 100mg/day 8 weeks vs 12 weeks
12 weeks recommended – 93% cure rate at 12 months (PP)
Based on 15 cases
No children, no macular PKDL, no safety data >4 weeks
Needs contraception >7 months in women of reproductive age
Adherence likely to be an issue – may lead to resistance
This regimen poses high direct and indirect costs for the patient and health care system

6. MSF treatment for PKDL in Bangladesh and India
Diagnosis:
Clinical symptoms + past VL + +ve rK39 test
Treatment:
AmBisome 30 mg/kg total dose (6 x 5 mg/kg 2/7, ambulatory)
Initially in Bangladesh, then started in India after WHO consultative meeting recommendations 2012
Subsequently AmBisome 15 mg/kg total dose (5 x 3 mg/kg 2/7, ambulatory) in Bangladesh
Ambulatory treatment over 3 weeks
End-points 12 months follow up, photograph assisted scoring
Safety monitored closely; particularly hypokalaemia

7. 30mg/kg AmBisome regimen for treatment of PKDL: Patient characteristics Bangladesh

8. 30mg/kg AmBisome regimen for treatment of PKDL: Patient characteristics India

9. Effectiveness and safety outcomes at 12 months
India: Of 50 patients completing 12 month follow up, 42 (84%) showed substantial or complete cure
Bangladesh: Of 63 patients completing 12 month follow up, 59 (93%) showed substantial or complete cure
Safety data (entire cohort):
Concerning incidence of hypokalaemia in Bangladesh
No rhabdomyolysis or other sequealae in either context
Treatment switched to 15mg/kg in Bangladesh
Hypokalaemia
India (n=113)
Bangladesh (n=110)
Number %
Mild ( mmol/L) 21
18.5% 53
49.1%
Moderate ( mmol/L) 8 7% 17
15.7%
Severe (<2.5 mmol/L) 1
0.9% 7
6.5%

10. 15mg/kg AmBisome regimen for treatment of PKDL in Bangladesh: A prospective observational study
Primary objective:
Evaluate effectiveness of AmBisome 15 mg/kg total dose at 12 months
3mg/kg given in 5 doses over 2-3 weeks
Secondary objective:
Evaluate safety of AmBisome 3mg/kg x 5 infusions (twice weekly)
Evaluate the occurrence of hypokalaemia
Evaluate at which point in time lesions start to respond to treatment.
Sample size: 275

11. PKDL lesion improvement during post-treatment follow up March 2015
73% substantial or complete improvement by 6 months
Excellent safety data – no SAE or severe hypokalaemia
12 month data collection has started

12. Limitations
Difficult to standardise assessment of improvement – very subjective
Irregular quality of photographs in 30mg/kg groups (improved in 15mg/kg)
Inclusion was clinical assessment based – negative parasitology did not preclude inclusion

13. Conclusions
30mg/kg AmBisome appears effective in the treatment of PKDL
Safety concerns of hypokalaemia in Bangladesh, although not seen in India
15mg/kg AmBisome appears safe, tolerable and showed good adherence in PKDL
Effectiveness appears to be similar to the higher dose – pending 12 month results becoming available
Urgent need for an alternative shorter course treatment exists for PKDL – AmBisome may be considered an appropriate option