蒿甲醚对血吸虫超微结构的影响

蒿甲醚是青蒿素的一个衍生物,不仅是有效的抗疟药,而且对血吸虫特别是血吸虫童虫亦有效,并已在20世纪末被发展为预防血吸虫病的药物.为了了解蒿甲醚的抗血吸虫作用,除观察其对血吸虫生化代谢的影响外,还用扫描电镜和透射电镜观察了蒿甲醚对感染人体的主要3种血吸虫,即日本血吸虫、曼氏血吸虫和埃及血吸虫超微结构的影响,结果表明蒿甲醚不仅损害血吸虫的皮层、感觉器和皮层结节,而且对虫的肌层、实质组织、肠上皮细胞和卵黄细胞等亦引起广泛的损害.该文综述了蒿甲醚对这3种血吸虫超微结构损害的观察结果,并进行了讨论.     

Histopathological changes in juvenile Schistosoma haematobium harboured in hamsters treated with artemether

Histopathological changes in juvenile Schistosoma haematobium, caused by artemether administered to the infected hamsters, were studied. Hamsters were infected with S. haematobium cercariae, and after 28 days, a single dose of artemether (300 mg/kg) was administered intragastrically. After 24 h, 72 h and 7 days, groups of two hamsters were sacrificed, and livers were removed, fixed and processed routinely, and examined by light microscopy. After 24 h, 93% of the schistosomulae examined showed degeneration, which included swelling of the tegument, adherence of inflammatory cells to the damaged tegument, collapsed and damaged intestine, and infiltration of inflammatory cells, predominantly lymphocytes. After 72 h, the intensity of damage increased, including severe swelling of the tegument, loss of definition in the internal structures, collapse of intestine accompanied by release of pigment particles to the parenchymal tissues, and emergence of dead schistosomulae. Seven days after treatment, the number of dead schistosomulae increased, and most of them developed to an early- or late stage of dead worm granuloma. Meanwhile, 12% of the schistosomulae showed a normal appearance, which suggested that those schistosomulae that had survived the treatment were recovered to normal. The results demonstrated that artemether effectively acts against the juvenile stages of S. haematobium and confirms earlier results with S. japonicum and S. mansoni.     

蒿甲醚对感染小鼠体内埃及血吸虫超微结构的影响

目的 观察蒿甲醚对小鼠体内埃及血吸虫成虫超微结构的损害。 方法 8只小鼠于感染埃及血吸虫尾蚴后81 d用单剂蒿甲醚400 mg/kg口服治疗。治后24 h、3 d、7 d和14 d各剖杀2只小鼠，用灌注法收集血吸虫，并按常规方法固定和处置虫体，作透射电镜观察。从另2只未治疗的感染小鼠体内取虫作对照。 结果 蒿甲醚对血吸虫皮层超微结构的损害主要是皮层基质的肿胀、溶解和空泡变化，基底膜消失和部份受损皮层破裂；在感觉器和皮层结节中，常见其内部结构广泛溶解。在肌层、实质组织、合体细胞和肠管上皮细胞中，查见局灶性或广泛的溶解、粗面内质网减少及线粒体空泡变化和变性。雌虫卵黄细胞的严重变化是空泡变化、粗面内质网减少、卵黄球融合以及受损卵黄细胞破溃等。上述雌、雄虫变化于感染小鼠用蒿甲醚治疗后24 h即可见到，并逐渐加重，3~7 d后最重。治后14 d，部分雌、雄虫仍示有超微结构的损害，但同时亦观察到受损虫组织的恢复。 结论 蒿甲醚对埃及血吸虫成虫的皮层和皮层下组织具有广泛和严重的超微结构损害。     

Tegumental changes in 21-day-old Schistosoma mansoni harboured in mice treated with artemether

Alterations in the tegument of 21-day-old Schistosoma mansoni, caused by artemether administered to the infected mice, were studied using scanning electron microscopy (SEM). Mice were infected with S. mansoni cercariae, and after 21 days a single dose of artemether (400 mg/kg) was administered intragastrically. After 24, 72 h and 7 days groups of three mice were killed and the schistosomules collected by perfusion, fixed and processed routinely, and examined by SEM. After 24 h, all male and female worms examined showed alterations in the tegument, characterised by swelling, vesiculation and fusion of tegumental ridges; peeling, erosion and collapse of damaged tegumental surface, and also destruction of the oral sucker and acetabulum. After 72 h, severe damage to the tegument was seen, usually including extensive peeling, swelling and vesiculation, and host leukocytes were adhered to the damaged surface. Some worms were surrounded by clusters of host leukocytes or had even disintegrated. Seven days after treatment, some schistosomules still showed severe tegumental damage, but in some cases the damage was less than at earlier times, which suggested that those schistosomules that had survived were beginning to recover. The ability of artemether to cause severe damage to the tegument correlates with its high efficacy in killing 21-day-old schistosomules.     

Schistosoma japonicum and S. mansoni: ultrastructural damage in the tegument and reproductive organs after treatment with levo- and dextro-praziquantel

Ultrastructural observations were made of changes in the tegument and reproductive organs of Schistosoma japonicum and S. mansoni from ICR mice after treatment with praziquantel (PZQ), levo-PZQ, and dextro-PZQ at a single oral dose of 500 mg/kg body weight. No marked difference in types and extent of lesions of the tegument of S. japonicum was found between the compounds regardless of the time of worm recovery after treatment. This was equally true of S. mansoni. Degeneration of the testis, ovary, and vitelline gland of S. japonicum was more prominent in worms administered PZQ and levo-PZQ than in those receiving dextro-PZQ. In S. mansoni, extensive regression of the reproductive organs was observed in male and female worms treated with PZQ and dextro-PZQ, while no serious damage was seen in worms treated with levo-PZQ.     

Effect of combined treatment with praziquantel and artemether on Schistosoma japonicum and Schistosoma mansoni in experimentally infected animals

Praziquantel and artemether are safe and efficacious antischistosomal drugs that act against different developmental stages of the parasite: praziquantel against adult worms and artemether against schistosomula. A combined treatment has been suggested as a strategy for transmission control. Recent laboratory experiments with rabbits with a mixed infection of Schistosoma japonicum parasites of different ages confirmed the effectiveness of a combination therapy. In the present work, we assessed the effect of a combined treatment on adult worms of S. japonicum and found significantly higher worm reduction rates than with a single dose of praziquantel. In a next step, we extended the study of the combined treatment to Schistosoma mansoni. A combined treatment with 75 mg/kg praziquantel and 150 mg/kg artemether was administered to hamsters infected with juvenile and adult S. mansoni. The two drugs, administered simultaneously or spaced by 6 h, 1, 3 or 7 days, resulted in significantly higher worm reduction rates than a single treatment with praziquantel. A combination therapy with increased doses of 100 mg/kg praziquantel and 300 mg/kg artemether showed very high worm reduction rates of 90% and above, however, some hamsters died in five different combined treatment experiments, suggesting that these drug concentrations were too high. We conclude that a combined treatment with praziquantel and artemether at the lower doses is safe and more effective than praziquantel alone, which forms a foundation for designing respective clinical trials in humans.     

蒿甲醚对感染小鼠体内埃及血吸虫皮层的损害

目的 评价蒿甲醚对小鼠体内埃及血吸虫皮层的损害作用。 方法 8只小鼠于感染埃及血吸虫尾蚴后81 d，用单剂蒿甲醚400 mg/kg口服治疗。治疗后1、3、7和14 d各剖杀2只小鼠，用灌注法收集血吸虫，并按常规方法固定和处置虫体，作扫描电镜观察。从另2只未作治疗的感染小鼠取虫作对照。 结果 用蒿甲醚治疗后24 h，雄虫的皮层结节肿大、破溃或从皮层上剥落; 在雄虫和雌虫的体表可查见有局灶性或广泛的皮层肿胀、融合、空泡变化、糜烂和剥落，以及感觉结构的破坏。治疗后3 d，雌、雄虫的皮层损害加重，最严重的损害为口吸盘肿胀和破溃，并查见皮层褶嵴有广泛和严重的肿胀、糜烂和剥落，以及雌虫盘状感觉结构的破坏。治疗后7至14 d，有些虫仍示有中或重度皮层损害，而有些仍存活的虫则示其大部分皮层已有明显恢复。 结论 蒿甲醚对埃及血吸虫的皮层具有广泛和严重的损害作用。     

Ultrastructural studies of the killing of schistosomula of Schistosoma mansoni by activated macrophages in vitro

Immunologically activated murine macrophages have been shown elsewhere to kill skin stage schistosomula of Schistosoma mansoni in vitro, in a manner analogous to the extracellular killing of tumour cell targets. In this study, the kinetics of the interaction between activated macrophages and larval targets and the resultant ultrastructural changes in parasite morphology that culminated in death have been analysed in detail. Unlike granulocyte-mediated schistosomular killing, macrophage-mediated cytotoxicity did not appear to be directed against the surface tissues of the parasite. Macrophages adhered only transiently following initiation of the cultures, yet changes in the subtegumental mitochondria and muscle cells of the larva were detected within the first hour of incubation. Progressive internal disorganisation followed rapidly, but the tegument and tegumental outer membrane remained intact, to form a 'shell' that maintained the general shape of the parasite. Such changes were recognised irrespective of whether the effector cell population comprised peritoneal macrophages activated by lymphokine treatment in vitro, or by infection with Mycobacterium bovis (strain BCG), or S. mansoni in vivo. That macrophages rather than contaminating granulocytes or lymphocytes, had mediated the observed damage was demonstrated by the use of a lymphokine treated macrophage cell line, IC-21. The observation that macrophage cytotoxicity is directed against internal organelles rather than the tegumental outer membrane of this multicellular target, may help to elucidate the general mechanism of extracellular killing by these cells.     

Schistosoma japonicum myosin: cloning, expression and vaccination studies with the homologue of the S. mansoni myosin fragment IrV-5

The Schistosoma japonicum homologue of the 62 kDa fragment of S. mansoni myosin (SmIrV-5), which has proved highly protective against S. mansoni infection in mice and rats, has been cloned and expressed as the full length 62 kDa equivalent, Sj62, and a truncated 44 kDa version, Sj44. DNA sequencing showed the Sj62 sequence to be 88.4% identical at the nucleic acid level and 96% identical in deduced amino acid sequence to that of SmIrV-5. The recombinant proteins (rSj44 and rSj62) were strongly recognized in Western blotting by sera from mice multiply vaccinated with UV-irradiated S. japonicum cercariae and weakly recognized by S. japonicum chronic infection mouse sera. Unlike SmIrV-5, mouse antisera against the recombinant S. japonicum proteins did not give positive recognition in immunofluorescence assay with the surface of newly transformed schistosomula of the homologous species, S. japonicum, nor did they react with S. mansoni schistosomula. However, the anti-rSj62 sera clearly localized the native antigen to the subtegumental muscle layers in male adult worm sections by immunoelectron microscopy. Vaccination of several groups of mice and/or rats with rSj44 and rSj62 incorporated into different adjuvants induced high titres of specific IgG but in only one experimental group was there a significant reduction in worm burden (27%, P < 0.05). The possible reasons for the disparity between the vaccination results presented here and those demonstrated in experiments using rSm62 (IrV-5) are discussed .     

Ultrastructure of cultured cells from Schistosoma japonicum

Ultrastructures and their dynamic changes of the cultured cells from Schistosoma japonicum were observed in the present experiments. Several types-including polygonal, round granular, deltaic fan-shaped and flagellated cells-were found in the cultures. The polygonal cells took a major ratio in the cultures from adult S. japonicum, while the majority from schistosomula was round granular cells. The ultrastuctures on the cell surface were different between the cells from adults and schistosomula. Some papilla-like tubercula, microvilli and pinocytotic vesicles were observed on the surface of adult cells, but none were found on schistosomula cells. However, more or less mitochondria, endoplasmic reticula, ribosomes and glycogen were observed in the cytoplasm of the cultured cells from both adults and schistosomula. Golgi complexes were rarely found. The nucleus was round, with round nucleolus inside and clear pores on the unit membrane. There was much lumpish heterochromatin located near to the nuclear membrane. Cells from different worm tissues had their own organelles. The germ cells, vitelline cells, flame cells, multinucleate subtegumental cells and nerve cells could be observed in the cultures from adults. The vitelline cells were the greatest in number and nerve cells were the least in number among them. Similarly, there were germ cells, sustentacular cells, flame cells, nerve cells, mast cells, muscle cells, multinucleate subtegumental cells, interstitial cells and penetration gland cells in the cultures from the schistomomula. In addition, a few division cells were also found. It indicated that the schistosomula cells had greater potential ability to proliferate than the adult cells in in vitro culture. Along with the prolongation of the culture time, degeneration of schistosomal cell occurred more and more. Generally, the electron density of cultures gradually got lower, the cristae of mitochondria blurred and disappeared and the mitochondria themselves swelled and finally vacuoled completely. Vitelline cells were most sensitive to the changes of the in vitro condition in all cultures. Their degeneration showed the following characteristics: (1) vitelline globules fused each other, the space between vitelline globules and the membrane surrounding them broadened gradually and vitelline globules were released and uncovered; (2) rough-surfaced endoplasmic reticula enlarged, vacuolated and the ribosomes dropped; and (3) the number and volume of lipid increased. The ultrastructural changes of most of the cultures from schistosomula had the following trends: (1) heterochromatin increased and euchromatin decreased gradually; and (2) endoplasmic reticula changed into short tubes and vacuoles and disappeared finally. The degenerative process of the cultures from S. japonicum consisted of necrosis according to the ultrastructural changes of the mitochondria, vitelline globules, chromatin and endoplasmic reticula within the cells. The changes of the above structures could be used to estimate whether the culture conditions were appropriate.     

The isolation of a 22 kDa band after SDS-PAGE of Schistosoma mansoni adult worms and its use to demonstrate that IgE responses against the antigen(s) it contains are associated with human resistance to reinfection

In schistosomiasis endemic areas, intensities of reinfection after treatment are greater amongst young children than amongst adults, and high levels of parasite-specific IgE are associated with resistance to reinfection in an age-dependent manner. Previously we have reported that, in Western blots, a 22 kDa band was recognized by human IgE and that the incidence and intensity of S. mansoni reinfection were significantly lower amongst individuals who had IgE against this band, compared with those who did not (Dunne et al. 1992). Here we report the isolation of a 22 kDa SDS-PAGE band, its incorporation into ELISA and the demonstration that levels of human anti-22 kDa IgE had a significant negative correlation with intensities of subsequent reinfection. Rabbit anti-22 kDa band serum recognized the outer tegument, gut tegument, and the collecting ducts and flame cells of adult worms. The 22 kDa band antigen(s) was also present in 'lung'- and 'post-lung' schistosomula stages of S. mansoni , and in S. haematobium , S. bovis and S. japonicum adult worms. Metabolic labelling of schistosomula and worms demonstrated the in vitro synthesis and release of 22 kDa antigens.     

用电穿孔法将绿色荧光蛋白基因导入日本血吸虫童虫并表达

目的探讨增强型绿色荧光蛋白(EGFP)基因在日本血吸虫童虫体内异源表达,以及电穿孔技术在血吸虫基因转化中应用的可能性。方法应用电穿孔技术将质粒pEGFP-C1导入机械转化的日本血吸虫童虫体内,提取分离体外培养48h童虫的基因组DNA、总RNA和全虫蛋白,分别用PCR、逆转录-聚合酶链反应(RT-PCR)和蛋白质印迹法(Western blotting)验证转基因在童虫体内的存在、转录和翻译。同时,使用激光共聚焦扫描显微镜对EGFP在童虫体内进行定位。结果PCR和RT-PCR分别成功扩增出760 bp和276 bp的预期大小的片段,Western blotting证实了EGFP基因在童虫体内的表达;激光共聚焦显微镜观察表明EGFP主要定位在童虫的皮层和副皮层,虫体前端尤为明显。结论电穿孔技术成功地将异源基因引入日本血吸虫童虫体内并获得表达。     

Cellular responses elicited by challenged schistosomula of Schistosoma japonicum in the skin of naive and chronically infected mice

Naive and chronically infected C57BL/6 mice were challenged percutaneously over the ear pinna with Schistosoma japonicum cercariae. After 15 hours, the number of EOS increased significantly in the skin of chronically infected mice. Inflammatory cells aggregated in the vicinity of schistosomula or entrapped intact and disintegrated schistosomula, forming granulocytic micro-abscesses in both groups. Ultrastructure studies revealed that flattened EOS tightly attached to the schistosomulum surface and degranulated. Local tegument damage occurred in the area of attachment. NEU adherence did not seem to be as intimate as EOS, and degranulation was not seen. The tegument of the attached schistosomulum remained normal. The result suggested that EOS appeared to be the efficient killer cell against skin phase schistosomula of S. japonicum.     

环孢素A体外抗AF18标记的曼氏血吸虫童虫的研究

目的　探讨环孢素A体外抗AF18标记的曼氏血吸虫童虫的作用以及虫体表膜流动性。　方法　制备童虫,环孢素A体外作用,AF18标记,荧光显微镜观察。　结果　童虫损伤或死亡,虫体逐渐从绿色变成黄色,虫体表面损伤。　结论　环孢素A增加童虫AF18的含量,减低童虫表膜流动性。     

环孢素A体外抗AF18标记的曼氏血吸虫童虫的研究

目的探讨环孢素A体外抗AF18标记的曼氏血吸虫童虫的作用以及虫体表膜流动性。方法制备童虫，环孢素A体外作用，AF18标记，荧光显微镜观察。结果童虫损伤或死亡，虫体逐渐从绿色变成黄色，虫体表面损伤。结论环孢素A增加童虫AF18的含量，减低童虫表膜流动性?     

日本血吸虫童虫表膜结合多肽的亲和筛选与初步鉴定

目的筛选噬菌体十二肽库中与日本血吸虫(Schistosoma japonicum)童虫表膜特异性结合的多肽并鉴定。方法利用噬菌体十二肽库与日本血吸虫活童虫靶分子之间的亲和力结合,经3轮吸附-洗脱-扩增,从末次回收的结合噬菌体中随机挑取20个克隆进行测序。根据测序结果 ,选取出现次数最多的噬菌体克隆作为目标噬菌体,免疫组化检测目的噬菌体,并回输到已感染日本血吸虫的小鼠体内,2.5h后处死小鼠,回收肝脏和日本血吸虫童虫,分别洗脱与肝脏和童虫结合的噬菌体,进行统计学分析。结果经3轮筛选后,噬菌体回收率从第1轮的0.77×10-8到第3轮的0.75×10-5,说明噬菌体得到了有效富集。DNA测序结果表明,20个噬菌体克隆中的15个克隆呈现QHPRIRKOOOOO序列。免疫组化结果显示,表达该序列的噬菌体能与童虫表膜有效结合;体内回输试验证实,该噬菌体能有效地靶向结合于体内日本血吸虫童虫表膜。结论筛选获得的短肽QHPRIRKOOOOO能有效地靶向结合日本血吸虫童虫表膜。     

蒿甲醚对曼氏血吸虫的作用:剂量与效应的关系和虫的形态学和组织病理学的变化

目的　应用感染曼氏血吸虫 (利比里亚株 )的小鼠观察蒿甲醚单剂量与效应的关系,虫体肝移及蒿甲醚所引起的虫的形态学和组织病理学变化。　方法　感染21d童虫的小鼠一次口服蒿甲醚12.5mg/kg至600mg/kg不同剂量 ,治后28d剖检观察各组虫数。感染46d或70d成虫的小鼠一次口服蒿甲醚40 0mg/kg后8～14d ,观察虫体肝移及其形态和组织病理学变化。　结果　蒿甲醚对21d童虫的最低有效剂量为200mg/kg ,减虫率为 81%。用蒿甲醚治疗后8h成虫开始肝移,3～7d全部肝移,14d有31%的虫返回肠系膜静脉。成虫虫体萎缩,咽部扩大,肠管膨胀及其色素减少。雌虫局部体表受损,白细胞附着,卵巢及卵黄腺变性退化,以及雄虫睾丸萎缩等。在肝内的虫体被嗜酸粒细胞为主的炎细胞包围和浸润。　结论　蒿甲醚对小鼠曼氏血吸虫21d童虫的最低有效剂量为200mg/kg ,可引起曼氏血吸虫成虫萎缩、退化或死亡。在肝内受损的虫体主要是被嗜酸粒细胞包围和侵袭所致。     

环孢素A体外抗曼氏血吸虫雄虫的时间生物学研究

目的：探讨环孢素Ａ体外抗曼氏血吸虫的作用。方法：ＭＦ１小鼠实验感染曼氏血吸虫６ｗｋ后，经主动脉和门静脉灌注收虫。将雄虫放入含有１μｇ／ｍｌ、１０μｇ／ｍｌ、１５μｇ／ｍｌ、２０μｇ／ｍｌ和２５μｇ／ｍｌ环孢素Ａ的１９９培养液中体外培养。用扫描电镜对药物所致的虫体皮层损害作时间生物学观察。结果：在体外，雄虫经１μｇ／ｍｌ环孢素Ａ作用后，体嵴的结构疏松；经１０μｇ／ｍｌ环孢素Ａ作用２４ｈ后，雄虫皮层肿胀；雄虫经１５μｇ／ｍｌ环孢素Ａ作用８ｈ－２４ｈ后，虫体皮层破溃；虫体经２０μｇ／ｍｌ药物作用２４ｈ后，雄虫皮层明显破溃；雄虫经２５μｇ／ｍｌ环孢素Ａ作用８ｈ后，皮层褶嵴受损；作用１６ｈ后，皮层肿胀；作用２４ｈ后，皮层极度破溃，皮棘脱落。药物所致的虫体皮层损害与剂量和时间呈依赖关系。结论：环孢素Ａ具有直接杀曼氏血吸虫的作用。     

青蒿琥酯抗日本血吸虫童虫和成虫作用的研究

目的 观察青蒿琥酯对不同阶段日本血吸虫的损害作用,揭示青蒿琥酯的杀虫机制.方法小鼠感染尾蚴18 d时给予青蒿琥酯300 mg/kg,24 h后灌注法收集童虫,并用紫外吸收法和Bradford标准曲线法测定青蒿琥酯对日本血吸虫18 d童虫DNA和蛋白质含量的影响;分别将10条虫体在含有3H胸腺嘧啶核苷的培养基中培养24 h后,用滤膜法和匀浆法测定青蒿琥酯对标记核苷掺入童虫DNA的影响;感染血吸虫尾蚴21 d的小鼠一次性灌服青蒿琥酯300 mg/kg,给药后21 d,灌注法收集成虫,观察青蒿琥酯对日本血吸虫成虫生殖器官大小及生殖细胞发育的影响;小鼠感染血吸虫33 d时给予同样的青蒿琥酯进行治疗,24 h和48 h后处死小鼠,将肝脏制作组织切片,在光镜下观察同等剂量青蒿琥酯引起的成虫肝移和形态学变化的影响.结果 青蒿琥酯体内作用18 d的虫体,24 h后,童虫的DNA和蛋白质含量均较对照组明显减少,减少率分别为23.0%和33.6%(P＜0.01);在含有3H胸腺嘧啶核苷的培养基中培养24 h后,童虫摄入标记的核苷及核苷掺入童虫DNA的量较对照组也明显减少,减少率分别为61.1%和40.8%(P＜0.01);21 d给药组小鼠体内雌虫卵巢的成熟、发育受到了抑制;药物作用于虫体33 d后能明显引起虫体形态的变化,特别是虫体体表.结论 青蒿琥酯能减少日本血吸虫童虫蛋白质和DNA的含量,能明显抑制虫体对标记核苷的摄入以及标记核苷掺入虫体DNA的量,能引起虫体体表明显的组织形态学变化,并且能抑制雌虫卵巢的发育,降低或抑制雌虫的产卵,能有效减轻血吸虫病的病情和控制传播.     

Randomized,double-blind,placebo-controlled trial of oral artemether for the prevention of patent Schistosoma haematobium infections

Artemether is an efficacious antimalarial drug that also displays antischistosomal properties. Laboratory studies have found that artemether curtails the development of adult worms of Schistosoma japonicum, S. mansoni and S. haematobium, and thus prevents morbidity. These findings have been confirmed in clinical trials for the former two parasites; administered orally once every 2-3 weeks, artemether significantly reduced the incidence and intensity of patent infections. Here, we present the first randomized, double-blind, placebo-controlled trial of artemether against S. haematobium, done in a highly endemic area of C?te d'Ivoire. Urine specimens from 440 schoolchildren were examined over 4 consecutive days, followed by two systematic praziquantel treatments 4 weeks apart. S. haematobium-negative children were randomized to receive 6 mg/kg artemether (N = 161) or placebo (N = 161). Medication was administered orally for a total of six doses once every 4 weeks. Adverse events were assessed 72 hours after medication, and perceived illness episodes were monitored throughout the study period. Incidence and intensity of S. haematobium infections, and microhematuria and macrohematuria were assessed 3 weeks after the final dosing. We also monitored malaria parasitemia and treated positive cases with sulfadoxine-pyrimethamine (SP). Oral artemether was well tolerated. The incidence of patent S. haematobium infections in artemether recipients was significantly lower than in placebo recipients (49% versus 65%, protective efficacy: 0.25, 95% CI: 0.08-0.38, P = 0.007). The geometric mean infection intensity in the artemether group was less than half that of the placebo recipients (3.4 versus 7.4 eggs/10 mL urine, P < 0.001). Heavy S. haematobium infections, microhematuria and macrohematuria, and the incidence of malaria parasitemia were all significantly lower in artemether recipients. In conclusion, previous findings of efficacy of artemether against S. japonicum and S. mansoni were confirmed for S. haematobium, although the protective efficacy was considerably lower. These findings enlarge the scope and potential of artemether and further contribute to discussions of its role as an additional tool for integrated schistosomiasis control.