Liposomal amphotericin B for complicated

Kala-azar in Eastern Sudan

How effective is current treatment?

Niven. A. Salih,1 Johan van Griensven,2 Annick Antierens,3 Francois Chappuis,4 Ann Mumina,1

Omar Hammam,1 Philippa Boule,3 Emilie Allirol,4 Mubarak Alnour,5 MousabSiddig Elhag,6

Marcel Manzi,7 Walter kizito,7 Rony Zachariah7

1 Medecins Sans Frontieres-Switzerland, North Sudan mission 2 Institute of Tropical Medicine,

Antwerp, Belgium 3 Medecins Sans Frontieres-Geneva – Operations/Medical Department,

Switzerland 4 Geneva University Hospital, Geneva, Switserland 5 Ministry of Health, Gedaref State,

Gedaref, Sudan 6 Federal Ministry of Health, Khartoum, Sudan 7 Medecins Sans Frontieres-

Luxembourg, Luxembourg

Kala-azar – “Visceral

leishmaniasis” Caused by a protozoan

parasite “Leishmania

donovani”

Transmitted by tiny

blood-sucking insects

“sand-fly”

Second largest global

parasitic killer – after

Malaria

Kala-azar

Hepatosplenomegaly + Pancytopenia Fever & Cachexia

Parasite migrates to:

• Liver

• Spleen

• Bone Marrow

VISCERAL

DEATH

Operational Challenges

Treatment: Since decades

= Sodium stibogluconate

Injections for 30 days

Unpredictable toxicity

High mortality

Growing resistance (India)

Vector: No effective

measures to eradicate the

sand-fly

KALA-AZAR

A NEGLECTED DISEASE

Liposomal Amphotericin B

(AmBisomeTM)

New safer drug

High efficacy / Low toxicity

Shorter duration – 10 days

First choice in high income countries

BUT

Evidence on efficacy in East Africa is limited

Gedaref state, East Sudan (2010)

MSF started a program

for diagnosing and

treating Kala-azar

(Tabarak Allah)

Vertical program

KA and coinfections

Hospital-based diagnosis

and treatment

MSF KA treatment program AmBisome is given only for complicated cases

High cost (400$/patient)

Limited availability

Study objectives

Among Kala-azar patients treated with

AmBisome, in Gedaref state, to report on:

Effectiveness and safety

Proportion of relapse

Methods

Study Design: Cohort study

Study site: MSF Tabarak

Allah treatment centre

Study population: KA

patients treated with

AmBisome (March 2010-

June 2012)

Kala-Azar - Diagnosis Parasitological - Gold standard - Bone marrow/Lymph nodes

Serological:

rK39 / DAT

Kala- Azar (KA) - Primary & Relapse

Primary KA: Newly

diagnosed cases

Relapses: Previously

treated cases presenting

again with the disease

AmBisome Complicated cases only

Severely ill / relapse / HIV / Pregnancy / ≤ 2 yrs or

≥ 45 yrs

Dose: 3mg/kg/day iv for 10 consecutive days

Initial cure:

Clinical improvement (after 10 days)

Parasitological “test of cure” (aspiration)

Definitive cure: No relapse in 6 months

Results (Jan 2010- June 2012)

Total cases 1823

Received AmBisome 380 (21%)

Primary cases 283 (75%)

Children < 2 yrs 98 (35%)

Advanced disease 88 (31%)

> 45 years 56 (20%)

Pregnancy 24 (9%)

SSG contraindicated 10 (4%)

HIV 7 (3%)

Relapses 97 (25%)

Results – Treatment outcomes

Primary cases Total 283

Initial cure 260 (93%) Slow responders 4 (1%)

Deaths 21 (7%) HIV – highest case fatality – 43%

Transfer out 2 (1%)

6 months outcome

Relapse 24 (8%)

Lost to follow up 101 (36%)

Results – Treatment outcomes

Relapse cases Total 97

Initial cure 93 (96%) Slow responders 8 (8%)

Deaths 3 (3%)

Transfer out 1 (1%)

6 months outcome

Relapse 10 (10%)

Lost to follow up 37 (38%)

Results - Safety

Side effects: mild and temporary

Eg. Shivering

No discontinuation of AmBisome due to

toxicity

No AmBisome related deaths

Conclusion

In a rural area of Gedaref state, Sudan:

AmBisome treatment appears effective

High initial cure rates

But relapses are a concern

The treatment is well tolerated and safe

Advocacy to reduce high costs (400 $/patient) and increase access is urgently needed

Recommendations

Recommendations

Relapses

Suggests a need for higher drug dosing or combination therapy ?

Lost to follow up is high

There is a need to investigate possible reasons (further research)

Acknowledgments

Patients and Staff of the

MSF programme

MSF-Union operational

research courses for

supporting this study