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- Title
Geographical Variation in the Response of Visceral Leishmaniasis to Paromomycin in East Africa: A Multicentre, Open-Label, Randomized Trial.
- Authors
Hailu, Asrat; Musa, Ahmed; Wasunna, Monique; Balasegaram, Manica; Yifru, Sisay; Mengistu, Getahun; Hurissa, Zewdu; Hailu, Workagegnehu; Weldegebreal, Teklu; Tesfaye, Samson; Makonnen, Eyasu; Khalil, Eltahir; Ahmed, Osama; Fadlalla, Ahmed; El-Hassan, Ahmed; Raheem, Muzamil; Mueller, Marius; Koummuki, Yousif; Rashid, Juma; Mbui, Jane
- Abstract
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. Findings: 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. Conclusion: 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. Author Summary: Visceral leishmaniasis (VL) is a fatal parasitic disease with 500,000 new cases each year according to WHO estimates. New and better treatment options are urgently needed in disease endemic areas due to the long courses, toxicity and development of resistance to current treatments. Recently, the antibiotic paromomycin was tested and registered in India to treat this disease. The current study describes a clinical trial to test the effectiveness of injectable paromomycin, either alone or in combination with the standard drug sodium stibogluconate in three East African countries—Sudan, Kenya and Ethiopia. The study showed that at the same paromomycin dose that was successfully used and registered in India, a far poorer outcome was obtained, particularly in Sudan, suggesting that there are either differences in the patients ability to respond to the drug or in the susceptibility of parasites in East Africa compared with those in India. However, no major safety concerns were noted with the treatment. Further research was initiated to see if a higher dose of paromomycin would perform better, especially in Sudan. The results of this and the performance of the combination arm will be reported later. Our study highlights the importance of considering geographical differences to treatment responses.
- Subjects
SUDAN; EAST Africa; ETHIOPIA; VISCERAL leishmaniasis; PARASITIC diseases; ENDEMIC diseases; DRUG resistance; DEVELOPING countries; AGGLUTINATION tests
- Publication
PLoS Neglected Tropical Diseases, 2010, Vol 4, Issue 10, p1
- ISSN
1935-2727
- Publication type
Article
- DOI
10.1371/journal.pntd.0000709