The drug tribendimidine seems to be as safe and effective as the drug of choice, praziquantel, against infection with the Southeast Asian liver fluke (Opisthorchis viverrini), providing almost complete egg elimination and a cure rate of 70%. By contrast, antimalarial drugs are ineffective and should not be recommended as treatment against O. viverrini infections. These are conclusions of the first study to assess the potential of these drugs against this neglected tropical disease, published Online First in The Lancet Infectious Diseases.
Opisthorchis is a neglected tropical disease caused by the human liver fluke O. viverrini. An estimated 67 million people are at risk, and 9 million are infected in Cambodia, Laos, and the northeastern parts of Thailand and Vietnam. Infection with O. viverrini causes a variety of conditions including bile duct cancers. Currently, praziquantel is the only drug treatment available and concerns are growing about the emergence of resistance.
The antimalarials artemether, artesunate, mefloquine, and the drug tribendimidine (used in China to treat hookworm) have shown potential against the infection in-vivo.
In this study, Jennifer Keiser from the Swiss Tropical and Public Health Institute, Basel, Switzerland and colleagues conducted a phase 2 trial to assess the safety and efficacy of these drugs compared with the standard drug treatment (praziquantel) in school children from Attapeu province in Laos, where prevalence of O. viverrini infection is higher than 50%.
125 children with parasitologically confirmed infection were randomly assigned to one of five treatment groups—mefloquine (25), artesunate (24), mefloquine-artesunate fixed drug combination (24), tribendimidine (27), and praziquantel (25). Efficacy was measured by cure rate and egg reduction rate 21 days after treatment.
The highest cure rate was seen in patients treated with tribendimidine (70%), followed by praziquantel (56%). By contrast, just 4% of patients taking mefloquine- artesunate were cured, compared with 4% taking artesunate, and no child receiving mefloquine was cured.
Additionally, the praziquantel and tribendimidine regimens were significantly more effective than the antimalarials at egg clearance.
All the treatments were generally well tolerated, and most side-effects were mild or moderate. Serious adverse events were only experienced by patients taking mefloquine or the mefloquine-artesunate combination and included vertigo, nausea, vomiting, and anxiety.
The authors conclude: "Tribendimidine shows promising activity against O. viverrini infection. Once preclinical studies have been completed, and if the drug is registered outside China, large scale clinical studies should be done in O. viverrini endemic settings."
Professor Jennifer Keiser, Swiss Tropical and Public Health Institute, Basel, Switzerland. T) +41 (61) 284 8218 E) Jennifer.keiser@unibas.ch
For full Article, see: http://press.thelancet.com/tlidliverfluke.pdf
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The Lancet Infectious Diseases