A double-blind field trial on the effects of artemether on Schistosoma japonicum infection in a highly endemic focus in southern China

Abstract

To further strengthen the evidence-base of artemether for the control of schistosomiasis japonica, a randomised controlled trial was carried out in the Poyang Lake region, a highly endemic area in southern China. A total of 783 individuals, aged 6–60 years, were enrolled. They were first given a single oral dose of praziquantel (50 mg/kg). Then, they were randomly assigned oral artemether (6 mg/kg) or placebo, administered once every 2 weeks for 9–11 doses, covering the entire transmission season for Schistosoma japonicum in 2004. Stool examination 1 month after the final dosing revealed eggs of S. japonicum in 3/373 (0.8%) of the artemether recipients and 56/361 (15.0%) in placebo recipients (χ² = 53.69, P < 0.001). Compared to the baseline, the geometric mean intensity of S. japonicum infection had decreased by 96.1% in the artemether group, and increased by 50.8% in the placebo group. No acute cases of schistosomiasis japonica were observed in the artemether group, whereas three such cases were reported from the placebo group. Compliance with regard to multi-doses of artemether and placebo was 84.9, and 77.9%, respectively. This study confirms that repeated oral artemether produces no drug-related adverse effects, significantly reduces incidence and intensity of patent S. japonicum infection and results in high compliance. Hence it can be used as an additional tool for the control of schistosomiasis japonica in the lake regions of China.

Introduction

One of the most important parasitic infections, both from the public health and clinical perspective, is schistosomiasis (Hotez et al., 1997). Schistosomiasis japonica is a serious disease, typified by long-term chronicity, with more than 40 million Chinese at risk of acquiring an infection (Chen and Feng, 1999). The clinical features include fever, headache and lethargy, and in advanced cases involvement of serious fibro-obstructive pathology leading to portal hypertension, ascites and hepatosplenomegaly is observed that can cause premature death (Ross et al., 2002). Infection remains of considerable public health significance despite 50 years of extraordinary and intensive efforts to control the disease. At present, it is estimated that approximately 850,000 people and several hundred thousand livestock, including 100,250 bovines, are infected (Ross et al., 2001, Zhou et al., 2005). There are over 30,000 cases of advanced disease with 8000 new cases reported annually (Jiang et al., 2002). The major of endemic foci are located in the marshland and lake regions of Southern China that cover a vast area of five provinces, i.e. Anhui, Hubei, Hunan, Jiangsu and Jiangxi. In addition, schistosome infection debilitates domestic livestock that are used for food and as farm animals in Southern China.

If provided regularly, praziquantel is highly effective in decreasing morbidity due to schistosomiasis, but this drug fails to prevent re-infection (Li et al., 2002). In addition, praziquantel cannot be used for prevention as it is effective only against adult worms and the very young developmental stage of the parasite, i.e. the schistosomulum (Xiao et al., 1987). Furthermore, decreased susceptibility to praziquantel has been observed in laboratory investigations after repeated passages of subcurative doses and in field studies carried out in Egypt and Senegal (Doenhoff et al., 2002). Hence, there is considerable discussion whether tolerance or resistance of the parasite to this drug has already been developed or might do so. Despite no clear-cut evidence to support these claims, it is apparent that further research and development of novel, orally active, broad spectrum and inexpensive drugs is a pressing need given that virtually no viable alternatives to praziquantel exist.

Derivatives of artemisinin (e.g. artemether and artesunate) have been used extensively for the treatment and control of malaria (Woodrow et al., 2005). The artemisinins are also active against S. japonicum and other human schistosome species, especially on 5–21-day-old juvenile worms (Xiao et al., 2002). To date several randomised controlled trials have been carried out with artemether against S. japonicum in different epidemiological settings and the key findings have been reviewed (Utzinger et al., 2001a, Xiao et al., 2002, Utzinger and Keiser, 2004). The aim of this study was to assess the efficacy of repeated administration of artemether in the control of S. japonicum infection and infection intensity during the transmission season in the lake region of China.