Parasitol Res (2012) 110:1563–1564 DOI 10.1007/s00436-011-2641-8
SHORT COMMUNICATION
The sensitivity of artesunate against Schistosoma japonicum decreased after 10 years of use in China? Rong Liu & Hui-Fen Dong & Ming-Sen Jiang
Received: 23 August 2011 / Accepted: 2 September 2011 / Published online: 13 September 2011 # Springer-Verlag 2011
Abstract Artesuante (AS) is a good chemoprophylactic drug for preventing against schistosome infection, but Hua et al. recently reported that the sensitivity of AS against Schistosoma japonicum decreased after 10 years of use in China. There are at least three problems, to our knowledge, making the finding suspicious or inconclusive in that report. In consideration of it as the first report about the emergence of potential artemisinin derivative-resistant S. japonicum to date and the possible severe influences of the emergence of AS-resistant S. japonicum on the future choice of chemoprophylactic drugs for preventing against S. japonicum infections in China, we write this comment and call for some more rigorous and convincing trials to confirm this finding further.
Hua et al. (2010, issue 107) reported a decreased sensitivity of artesunate (AS) against Schistosoma japonicum after 10 years of use in China, based on the result of a randomized, double-blind, placebo-controlled study to evaluate the efficacy of “a combination of AS and praziquantel (PZQ)” for the prevention of S. japonicum infection (Hua et al. 2010). There are at least three problems, to our knowledge, which make the finding suspicious or inconclusive in this report. The first problem
R. Liu (*) : H.-F. Dong : M.-S. Jiang (*) Department of Medical Parasitology, School of Basic Medical Science, Wuhan University, Wuhan 430071, China e-mail:
[email protected] e-mail:
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is that the randomization method is not the best — they roughly divided randomly three sub-villages, namely, Dongxie, Xixie, and Chuankuijia, affiliated to Zhaoyang village, Nanji Township, Xinjian County, Jiangxi Province, into three groups: Administration I group, Administration II group and Placebo group, and then selected the participants, ignoring the condition that the baseline infection levels among the included participants of the three groups differed obviously, i.e., 26.2%, 14.9% and 17.2%, respectively. If the authors took P=0.17 of the χ2 test of the three infection levels as their reason, which is only our speculation, then it is unreasonable as they may have ignored an important fact, that is, the baseline infection levels were the exact values of the included participants of each group — but not estimations of the overall of each group. Thus, the differences of baseline infection levels among the three groups should not be ignored, as the remaining schistosome in participants after a single oral dose of PZQ treatment are likely to influence the subsequent prevention efficacy evaluation, in the fact that a single dose of PZQ cannot completely eliminate the schistosome. The best randomization method, we believe, is to allocate each participant who met the inclusion criteria from the above three villages completely randomly by generating random codes or drawing lots into three groups. The second problem is the contradictory statements between the study design “a randomized, double-blind, placebo-controlled study to evaluate the efficacy of a combination of AS and PZQ for the prevention of S. japonicum infection” and the drug administration. The study was aimed to evaluate the efficacy of a combination of AS and PZQ for the prevention of S. japonicum infection, but in fact, a single oral dose of PZQ at 40 mg/kg received by each subject (including the
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participants in the placebo group of course) was to eliminate any possible infections before enrollment, and only AS was received by the administration groups in the subsequent trial. Thus, it is obviously not an AS + PZQ vs. placebo-controlled trial (Inyang-Etoh et al 2009; Xia et al 2000). The third problem is, if this study was aimed to evaluate the efficacy of AS (or AS + PZQ) for the prevention of S. japonicum infection, any possible previous infections should be eliminated and then confirmed by examination (unnecessary for the persons without previous exposure to infected water), and any subject with egg-positive result must be excluded before entering into the next step. This is an essential task, but is not conducted in this study. In addition, there is a minor typing error on “June 31, 2007” in the “Method of drug administration” part of the article, which was a day that does not exist in the calendar. These problems, we believe, can introduce doubts on the credibility of the result. In consideration of it as the first report about the emergence of a potential artemisinin-derivate-resistance S. japonicum to date, and
Parasitol Res (2012) 110:1563–1564
the possible severe influences of the emergence of ASresistance S. japonicum on the future choice of chemoprophylactic drugs for preventing S. japonicum infections in China (Xiao 2005), more rigorous and convincing trials are needed to confirm this finding further.
References Hua HY, Liang YS, Zhang Y, Wei JF, Guo HX (2010) The sensitivity of artesunate against Schistosoma japonicum decreased after 10 years of use in China. Parasitol Res 107:873–878 Inyang-Etoh PC, Ejezie GC, Useh MF, Inyang-Etoh EC (2009) Efficacy of a combination of praziquantel and artesunate in the treatment of urinary schistosomiasis in Nigeria. Trans R Soc Trop Med Hyg 103:38–44 Xia CS, Zhao XY, Liu YF, Jiang ZH, Li NP (2000) Observation of the efficacy on schistosomiasis prevention with artesunate and praziquantel. J Prev Med Chin PLA 18:120–121 (in Chinese) Xiao SH (2005) Development of antischistosomal drugs in China, with particular consideration to praziquantel and the artemisinins. Acta Trop 96:153–167
