A double-blind field trial on the effects of artemether on Schistosoma japonicum infection in a highly endemic focus in southern 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.
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Study area and population
The study was carried out in Xigang village located in the Poyang Lake region of Yugan county, Jiangxi province, which is hyper-endemic for S. japonicum. The prevalence of infection among humans living here has been estimated between 10 and 20% in the period 2000–2004 with part-time fishing as the main source of exposure. A previously developed and validated questionnaire was used to collect information on relevant baseline data of all individuals aged 6–60 years (Ross et al., 1998). This
Water exposure
During the transmission season, water exposure was assessed once every 2 weeks. In the artemether group, a total of 4389 person-time was interviewed, and 90.5% of the participants reported water contact. In the placebo group, 4180 person-time were interviewed with 92.0% of the subjects reporting water contact. There was no significant difference in reported water exposure between the two groups (P > 0.05).
Compliance with regard to treatment
Fig. 1 shows the trial profile. Of the 857 originally selected subjects, 74 (8.6%) withdrew
Discussion
The effect of artemisinin against S. japonicum infection was first reported in 1980 by a group of Chinese scientists (Chen et al., 1980). In fact, the drug, administered to various animals species experimentally infected with S. japonicum, resulted in marked reductions in worm burdens, as compared with untreated control animals. In 1982, antischistosomal properties were also reported for artemether (a methyl ether derivative of dihydroartemisinin). Mice or dogs infected with S. japonicum and
Acknowledgements
This investigation received financial support from the UNICEF/UNDP/World Bank Special Programme for Research and Training in Tropical Diseases (TDR), Wellcome Trust and NHMRC, Australia. We are grateful to the doctors and nurses at the related local antischistosomiasis hospitals for their kind support.
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