Geographical variation in the response of visceral leishmaniasis to paromomycin in East Africa: a multicentre, open-label, randomized trial.
BACKGROUND
Visceral leishmaniasis (VL) is a major health problem in developing countries. The untreated disease is fatal, available treatment is expensive and often toxic, and drug resistance is increasing. Improved treatment options are needed. Paromomycin was shown to be an efficacious first-line treatment with low toxicity in India.


METHODS
This was a 3-arm multicentre, open-label, randomized, controlled clinical trial to compare three treatment regimens for VL in East Africa: paromomycin sulphate (PM) at 15 mg/kg/day for 21 days versus sodium stibogluconate (SSG) at 20 mg/kg/day for 30 days; and the combination of both dose regimens for 17 days. The primary efficacy endpoint was cure based on parasite-free tissue aspirates taken 6 months after treatment.


RESULTS
Overall, 135 patients per arm were enrolled at five centres in Sudan (2 sites), Kenya (1) and Ethiopia (2), when the PM arm had to be discontinued due to poor efficacy. The trial has continued with the higher dose of PM as well as the combination of PM and SSG arms. These results will be reported later. Baseline patient characteristics were similar among treatment arms. The overall cure with PM was significantly inferior to that with SSG (63.8% versus 92.2%; difference 28.5%, 95%CI 18.8% to 38.8%, p<0.001). The efficacy of PM varied among centres and was significantly lower in Sudan (14.3% and 46.7%) than in Kenya (80.0%) and Ethiopia (75.0% and 96.6%). No major safety issues with PM were identified.


CONCLUSIONS
The efficacy of PM at 15 mg/kg/day for 21 days was inadequate, particularly in Sudan. The efficacy of higher doses and the combination treatment warrant further studies.
Addis Ababa University, Addis Ababa, Ethiopia.
Asrat
A
Hailu
Ahmed
A
Musa
Monique
M
Wasunna
Manica
M
Balasegaram
Sisay
S
Yifru
Getahun
G
Mengistu
Zewdu
Z
Hurissa
Workagegnehu
W
Hailu
Teklu
T
Weldegebreal
Samson
S
Tesfaye
Eyasu
E
Makonnen
Eltahir
E
Khalil
Osama
O
Ahmed
Ahmed
A
Fadlalla
Ahmed
A
El-Hassan
Muzamil
M
Raheem
Marius
M
Mueller
Yousif
Y
Koummuki
Juma
J
Rashid
Jane
J
Mbui
Geoffrey
G
Mucee
Simon
S
Njoroge
Veronica
V
Manduku
Alice
A
Musibi
Geoffrey
G
Mutuma
Fredrick
F
Kirui
Hudson
H
Lodenyo
Dedan
D
Mutea
George
G
Kirigi
Tansy
T
Edwards
Peter
P
Smith
Lawrence
L
Muthami
Catherine
C
Royce
Sally
S
Ellis
Moses
M
Alobo
Raymond
R
Omollo
Josephine
J
Kesusu
Rhoda
R
Owiti
John
J
Kinuthia
D000293:Adolescent; D000328:Adult; D000351:Africa, Eastern; D000981:Antiprotozoal Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D005260:Female; D005843:Geography; D006801:Humans; D007893:Leishmania donovani / Q000302:isolation & purification*; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010303:Paromomycin / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D055815:Young Adult
D000981:Antiprotozoal Agents; D010303:Paromomycin