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Efficacy and safety of artemether in the treatment of chronic fascioliasis in Egypt: exploratory phase-2 trials
- Source :
- PLoS Neglected Tropical Diseases, PLoS Neglected Tropical Diseases, Vol 5, Iss 9, p e1285 (2011), PLoS neglected tropical diseases
- Publication Year :
- 2011
-
Abstract
- Background Fascioliasis is an emerging zoonotic disease of considerable veterinary and public health importance. Triclabendazole is the only available drug for treatment. Laboratory studies have documented promising fasciocidal properties of the artemisinins (e.g., artemether). Methodology We carried out two exploratory phase-2 trials to assess the efficacy and safety of oral artemether administered at (i) 6×80 mg over 3 consecutive days, and (ii) 3×200 mg within 24 h in 36 Fasciola-infected individuals in Egypt. Efficacy was determined by cure rate (CR) and egg reduction rate (ERR) based on multiple Kato-Katz thick smears before and after drug administration. Patients who remained Fasciola-positive following artemether dosing were treated with single 10 mg/kg oral triclabendazole. In case of treatment failure, triclabendazole was re-administered at 20 mg/kg in two divided doses. Principal Findings CRs achieved with 6×80 mg and 3×200 mg artemether were 35% and 6%, respectively. The corresponding ERRs were 63% and nil, respectively. Artemether was well tolerated. A high efficacy was observed with triclabendazole administered at 10 mg/kg (16 patients; CR: 67%, ERR: 94%) and 20 mg/kg (4 patients; CR: 75%, ERR: 96%). Conclusions/Significance Artemether, administered at malaria treatment regimens, shows no or only little effect against fascioliasis, and hence does not represent an alternative to triclabendazole. The role of artemether and other artemisinin derivatives as partner drug in combination chemotherapy remains to be elucidated.<br />Author Summary Fasciola hepatica and F. gigantica are two liver flukes that parasitize herbivorous large size mammals (e.g., sheep and cattle), as well as humans. A single drug is available to treat infections with Fasciola flukes, namely, triclabendazole. Recently, laboratory studies and clinical trials in sheep and humans suffering from acute fascioliasis have shown that artesunate and artemether (drugs that are widely used against malaria) also show activity against fascioliasis. Hence, we were motivated to assess the efficacy and safety of oral artemether in patients with chronic Fasciola infections. The study was carried out in Egypt and artemether administered according to two different malaria treatment regimens. Cure rates observed with 6×80 mg and 3×200 mg artemether were 35% and 6%, respectively. In addition, high efficacy was observed when triclabendazole, the current drug of choice against human fascioliasis, was administered to patients remaining Fasciola positive following artemether treatment. Concluding, monotherapy with artemether does not represent an alternative to triclabendazole against fascioliasis, but its role in combination chemotherapy regimen remains to be investigated.
- Subjects :
- Male
Administration, Oral
Pilot Projects
Pharmacology
Gastroenterology
Feces
0302 clinical medicine
Artemether
Artemisinin
Child
Anthelmintics
0303 health sciences
lcsh:Public aspects of medicine
Combination chemotherapy
Middle Aged
Artemisinins
3. Good health
Triclabendazole
Treatment Outcome
Infectious Diseases
Child, Preschool
Medicine
Egypt
Female
medicine.drug
Research Article
Neglected Tropical Diseases
Adult
Veterinary Medicine
medicine.medical_specialty
Fascioliasis
Drugs and Devices
lcsh:Arctic medicine. Tropical medicine
Adolescent
lcsh:RC955-962
030231 tropical medicine
610 Medicine & health
03 medical and health sciences
Young Adult
Pharmacotherapy
Internal medicine
parasitic diseases
medicine
Animals
Humans
Dosing
Adverse effect
Parasite Egg Count
Aged
030306 microbiology
business.industry
Public Health, Environmental and Occupational Health
lcsh:RA1-1270
10060 Epidemiology, Biostatistics and Prevention Institute (EBPI)
2739 Public Health, Environmental and Occupational Health
2725 Infectious Diseases
Fasciola
Clinical trial
Veterinary Science
business
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- PLoS Neglected Tropical Diseases, PLoS Neglected Tropical Diseases, Vol 5, Iss 9, p e1285 (2011), PLoS neglected tropical diseases
- Accession number :
- edsair.doi.dedup.....50bb2e63561dcafeee542f1c19b1e187
- Full Text :
- https://doi.org/10.5167/uzh-54269