收稿日期: 2023-11-03
修回日期: 2024-01-27
网络出版日期: 2024-04-24
Therapeutic effect of once and twice doses of albendazole for soil-transmitted helminth infection
Received date: 2023-11-03
Revised date: 2024-01-27
Online published: 2024-04-24
目的 观察单次和双次阿苯达唑治疗人体土源性线虫感染的疗效。方法 2015年10月—2016年1月,选择云南省西双版纳州勐海县布朗山乡5所小学2~6年级的小学生进行基线调查,连续2 d收集粪样,每人每天1份,每份粪样采用Kato-Katz法制作3张加藤片镜检,结果为阳性(蛔虫、钩虫、鞭虫单一或混合感染)的学生接受阿苯达唑治疗(一次口服400 mg)。服药后3 d连续2 d收集粪样并镜检。4周后同一批学生再次服用阿苯达唑片剂400 mg,3 d后连续2 d收集粪样并镜检。2次服药后均同时开展问卷调查,统计不良反应情况。经2次服药后仍然阳性的学生再服用阿苯达唑片剂治疗1次。将5所小学按行政村归纳,统计不同行政村鞭虫感染治疗疗效。率的比较采用卡方检验。结果 5所学校共调查438人,土源性线虫感染率82.19%(360/438)。男生感染率为79.19%(175/221),女生为85.25%(185/217),差异无统计学意义(χ2 = 2.754,P > 0.05);布朗族、拉祜族、哈尼族、其他民族学生土源性线虫感染率分别为89.79%(299/333)、90.57%(48/53)、21.43%(9/42)、4/10(χ2 = 133.781,P < 0.05);2~6年级学生土源性线虫感染率分别为73.97%(54/73)、90.38%(94/104)、73.56%(64/87)、87.50%(28/32)、84.51%(120/142)(χ2 = 13.700,P < 0.05)。蛔虫、钩虫、鞭虫感染率分别为52.51%(230/438)、35.39%(155/438)、73.29%(321/438),其中第1次服药后蛔虫、钩虫、鞭虫感染治愈率分别为94.24%(180/191)、63.64%(77/121)、2.64%(7/265),第2次服药后蛔虫、钩虫、鞭虫感染治愈率分别为98.77%(161/163)、91%(91/100)、6.33%(14/221)。蛔虫、钩虫、鞭虫感染者服用1、2次阿苯达唑治愈率差异均有统计学意义(χ2 = 5.107、22.487、3.976,P < 0.05)。蛔虫、钩虫、鞭虫轻、中、重度感染者两次服药后治愈率差异均无统计学意义(第一次服药χ2 = 3.218、3.930、4.050,P > 0.05;第二次服药χ2 = 1.745、1.902、0.329,P > 0.05)。第1次服药后觉得吞药片困难、头晕、恶心、腹泻、呕吐等不良反应的发生率依次为11.47%(39/340)、10.88%(37/340)、16.76%(57/340)、7.65%(26/340)、1.47%(5/340)。第2次服药不良反应发生率接近第1次,两次服药各项不良反应发生率差异均无统计学意义。按照学校所在行政村分析,第2次服药后吉良小学感染鞭虫的学生治愈率为12.68%(9/71),高于曼囡小学(3.60%,4/111)(χ2 = 5.374,P < 0.05)。结论 阿苯达唑单次疗法对蛔虫感染有较好疗效;双次疗法对蛔虫和钩虫的驱虫效果均更好,且不增加不良反应的发生率。用阿苯达唑治疗中、重度的蛔虫、钩虫感染者无需增加剂量。阿苯达唑对鞭虫治疗效果较差,不宜单独使用阿苯达唑治疗鞭虫感染者。
严信留 , 杜尊伟 , 杨亚明 , 汪丽波 , 吴方伟 , 李奔福 , 李鸿斌 , 陈然 , 字金荣 , 彭佳 , 蔡璇 , 保雪莹 , 唐小英 , 杨恒林 . 单次和双次阿苯达唑治疗土源性线虫感染的疗效观察[J]. 中国寄生虫学与寄生虫病杂志, 2024 , 42(2) : 204 -210 . DOI: 10.12140/j.issn.1000-7423.2024.02.011
Objective To evaluate the efficacy of once and twice doses of albendazole in treating human soil-transmitted helminth infections. Methods From October 2015 to January 2016, school students of grades 2-6 in 5 primary schools were selected to participate baseline survey (in Blang Mountain Township, Menghai County, Xishuangbanna Prefecture, Yunnan Province. Fecal samples were collected for two consecutive days (one sample per day), each of which was used to prepare three slides and examined using Kato-Katz method by microscopy. Students with fecal egg-positive finding (Ascaris, hookworm, Trichuris single or mixed infections) are treated with albendazole (400 mg single dose). Three days after treatment, fecal samples were collected in consecutive 2 days. After 4 weeks, the same group of students received additional single dose of 400 mg albendazole and their fecal samples were collected 3 days after dosing and examined. A questionnaire survey was conducted at the same time of two medications to assess the adverse reactions. Students who were still egg-positive after twice dosing were treated with albendazole once more. The examinees of the five primary schools were summarized according to administrative villages to evaluste the therapeutic effect on Trichuris infection in different villages. The comparison of rates is conducted using χ2 test. Results A total of 438 people from 5 schools were investigated, and the infection rate of soil-derived nematodes was 82.19% (360/438). The infection rate was 79.19% (175/221) in boys and 85.25% (185/217) in girls, with no significant difference (χ2 = 2.754, P > 0.05). The infection rates of soil-transmitted helminth were 89.79% (299/333), 90.57% (48/53), 21.43% (9/42), 4/10 (χ2 = 133.781, P < 0.05) among the Blang, Lahu, Hani and other ethnological populations, respectively. The infection rates were 73.97% (54/73), 90.38% (94/104), 73.56% (64/87), 87.50% (28/32), 84.51% (120/142), respectively (χ2 = 13.700, P < 0.05). The infection rates of Ascaris, hookworm and Trichuris were 52.51% (230/438), 35.39% (155/438) and 73.29% (321/438), respectively. The cure rates of Ascaris, hookworm and Trichuris infection after the first dose were 94.24% (180/191), 63.64% (77/121) and 2.64% (7/265), respectively. The cure rates of Ascaris, hookworm and Trichuris infection after the second dose were 98.77% (161/163), 91% (91/100) and 6.33% (14/221), respectively. There was a significant difference in the cure rates of patients with Ascaris, hookworm and Trichuris who took albendazole once and twice (χ2 = 5.107, 22.487, 3.976, P < 0.05). There was no significant difference in the cure rates of mild, moderate and severe patients with Ascaris, hookworm and Trichuris after two doses (the first treatment χ2 = 3.218, 3.930, 4.050, P > 0.05; the second treatment χ2 = 1.745, 1.902, 0.329, P > 0.05). The incidence of adverse reactions such as difficulty swallowing pills, dizziness, nausea, diarrhea and vomiting after the first dose was 11.47% (39/340), 10.88% (37/340), 16.76% (57/340), 7.65% (26/340) and 1.47% (5/340), respectively. The incidence of adverse reactions in the second dose was close to that in the first dose, and there was no statistical significance in the incidence of adverse reactions between the two doses. According to the analysis of the village where the school was located, the cure rate of the students infected with Trichuris was 12.68% (9/71) in Kira Primary School after the second dose, which was higher than that in Mannian Primary School (3.60%, 4/111) (χ2 = 5.374, P < 0.05). Conclusion Albendazole single therapy showed good effect on Ascaris infection, while double therapy presented a better deworming effect on Ascaris and hookworm infection without increasing the frequency of adverse reactions. It is unnecessary to increase the dosage of albendazole for treating moderate and severe Ascaris and hookworm infections. Albendazole is not effective for treating Trichuris, thus it is not advisable to use albendazole alone for treatment of Trichuris infection.
| [1] | Vaz Nery S, Qi J, Llewellyn S, et al. Use of quantitative PCR to assess the efficacy of albendazole against Necator americanus and Ascaris spp. in Manufahi District, Timor-Leste[J]. Parasit Vectors, 2018, 11(1): 373. |
| [2] | World Health Organization. Neglected tropical diseases: global impact and response[M]. Beijing: People’s Medical Publishing House, 2011. (in Chinese) |
| (世界卫生组织. 被忽视的热带病: 全球影响与防治对策[M]. 北京: 人民卫生出版社, 2011.) | |
| [3] | World Health Organization. Soil-transmitted helminthiases: number of children treated in 2014[J]. Wkly Epidemiol Rec, 2015, 90(51/52): 705-711. |
| [4] | Pullan RL, Smith JL, Jasrasaria R, et al. Global numbers of infection and disease burden of soil transmitted helminth infections in 2010[J]. Parasit Vectors, 2014, 7: 37. |
| [5] | Wu ZX, Yang LD. Chemotherapy for geoheminthiasis[J]. J Public Health Prev Med, 2006, 17(1): 75-77. (in Chinese) |
| (吴中兴, 杨连第. 土源性蠕虫病的化学药物治疗[J]. 公共卫生与预防医学, 2006, 17(1): 75-77.) | |
| [6] | Wu ZX, Xu SE, Jin LQ. Curative effect of ivermectin on hookworm infection and observation on the ultrastructure of the worm[J]. Endem Dis Bull, 2003(1): 9-11, 97, 98. (in Chinese) |
| (吴中兴, 许世锷, 金立群. 伊维菌素对钩虫感染的疗效及对虫体超微结构的影响[J]. 地方病通报, 2003(1): 9-11, 97, 98.) | |
| [7] | Chen JY, Sun FH, Qian YX, et al. Clinical observation of Ivermectin in the treatment of intestinal nematode infections[J]. Chin J Zoonoses, 2000(3): 117-118. (in Chinese) |
| (陈锦英, 孙凤华, 钱益新, 等. 伊维菌素治疗肠道线虫感染的临床观察[J]. 中国人兽共患病杂志, 2000(3): 117-118.) | |
| [8] | Fang YY, Liang WJ, ZHANG QM, et al. Observation on the efficacy of ivermectin for treatment of intestinal nematode infections[J]. Chin J Parasit Dis Con, 2001, 14(3): 194-196. (in Chinese) |
| (方悦怡, 梁文佳, 张启明, 等. 伊维菌素治疗肠道线虫病的临床观察[J]. 中国寄生虫病防治杂志, 2001, 14(3): 194-196.) | |
| [9] | Du ZW, Jiang JY, Zhou H, et al. Efficacy of different doses of albendazole and mebendazole against common soil-transmitted helminths and Taenia spp.: a randomized controlled trial[J]. J Pathog Biol, 2012, 7(5): 360-362, 366. (in Chinese) |
| (杜尊伟, 姜进勇, 周卉, 等. 不同剂量阿苯达唑和甲苯咪唑对土源性线虫感染疗效的随机对照试验[J]. 中国病原生物学杂志, 2012, 7(5): 360-362, 366.) | |
| [10] | Wu ZX, Fang YY, Liu YS. Effect of a novel drug: enteric coated tribendimidine in the treatment of intestinal nematode infections[J]. Chin J Parasitol Parasit Dis, 2006, 24(1): 23-26. (in Chinese) |
| (吴中兴, 方悦怡, 刘宜升. 新药三苯双脒肠溶片治疗肠道线虫感染的效果观察[J]. 中国寄生虫学与寄生虫病杂志, 2006, 24(1): 23-26.) | |
| [11] | Wu ZX, Qian YX. Therapeutic effect of tribendimidine combined with ivermectin against human intestinal nematode infection[J]. Parasitoses Infect Dis, 2003, 1(2): 59-61. (in Chinese) |
| (吴中兴, 钱益新. 三苯双脒和伊维菌素伍用驱治肠道线虫感染的疗效观察[J]. 寄生虫病与感染性疾病, 2003, 1(2): 59-61.) | |
| [12] | Ministry of Health of the People’s Republic of China. Handbook of control of intestinal parasitic diseases[M]. Fuzhou: Fujian Education Press, 1996: 254-255. (in Chinese) |
| (中华人民共和国卫生部. 肠道寄生虫病防制手册[M]. 福州: 福建教育出版社, 1996: 254-255.) | |
| [13] | World Health Organization. Guideline: preventive chemotherapy to control soil-transmitted helminths infections in at risk population groups[R]. Geneva: World Health Organization, 2017. |
| [14] | World Health Organization. Preventive chemotherapy for helminth diseases: progress report, 2014[J]. Wkly Epidemiol Rec, 2016, 91(8): 93-103. |
| [15] | Speich B, Ame SM, Ali SM, et al. Efficacy and safety of nitazoxanide, albendazole, and nitazoxanide-albendazole against Trichuris trichiura infection: a randomized controlled trial[J]. PLoS Negl Trop Dis, 2012, 6(6): e1685. |
| [16] | Keller L, Palmeirim MS, Ame SM, et al. Efficacy and safety of ascending dosages of moxidectin and moxidectin-albendazole against trichuris trichiura in adolescents: A randomized controlled trial[J]. Clin Infect Dis. 2020, 70(6): 1193-1201. |
| [17] | Wang LD. Investigation on the status of major human parasitic diseases in China[M]. Beijing: People’s Medical Publishing House, 2008: 10-11. (in Chinese) |
| (王陇德. 全国人体重要寄生虫病现状调查[M]. 北京: 人民卫生出版社, 2008: 10-11.) | |
| [18] | Vercruysse J, Behnke JM, Albonico M, et al. Assessment of the anthelmintic efficacy of albendazole in school children in seven countries where soil-transmitted helminths are endemic[J]. PLoS Negl Trop Dis, 2011, 5(3): e948. |
| [19] | Nikolay B, Brooker SJ, Pullan RL. Sensitivity of diagnostic tests for human soil-transmitted helminth infections: a meta-analysis in the absence of a true gold standard[J]. Int J Parasitol, 2014, 44(11): 765-774. |
| [20] | Barda B, Zepherine H, Rinaldi L, et al. Mini-FLOTAC and Kato-Katz: helminth eggs watching on the shore of Lake Victoria[J]. Parasit Vectors, 2013, 6(1): 220. |
| [21] | Montresor A. Cure rate is not a valid indicator for assessing drug efficacy and impact of preventive chemotherapy interventions against schistosomiasis and soil-transmitted helminthiasis[J]. Trans R Soc Trop Med Hyg, 2011, 105(7): 361. |
| [22] | Levecke B, Mekonnen Z, Albonico M, et al. The impact of baseline faecal egg counts on the efficacy of single-dose albendazole against Trichuris trichiura[J]. Trans R Soc Trop Med Hyg, 2012, 106(2): 128-130. |
| [23] | Khurana S, Sethi S. Laboratory diagnosis of soil transmitted helminthiasis[J]. Trop Parasitol, 2017, 7(2): 86-91. |
| [24] | Lamberton PHL, Jourdan PM. Human ascariasis: diagnostics update[J]. Curr Trop Med Rep, 2015, 2(4): 189-200. |
| [25] | Knopp S, Rinaldi L, Khamis IS, et al. A single FLOTAC is more sensitive than triplicate Kato-Katz for the diagnosis of low-intensity soil-transmitted helminth infections[J]. Trans R Soc Trop Med Hyg, 2009, 103(4): 347-354. |
| [26] | Cools P. Diagnostic performance of a single and duplicate Kato-Katz, Mini-FLOTAC, FECPAKG2 and qPCR for the detection and quantification of soil transmitted helminths in three endemic countries. Hotez P. Measuring neglect[J]. PLoS Negl Trop Dis, 2007, 1(2): e118. |
| [27] | Moser W, Schindler C, Keiser J. Efficacy of recommended drugs against soil transmitted helminths: systematic review and network meta-analysis[J]. BMJ. 2017(358): j4307. |
| [28] | Kwa MS, Veenstra JG, Roos MH. Benzimidazole resistance in Haemonchus contortus is correlated with a conserved mutation at amino acid 200 in beta-tubulin isotype 1[J]. Mol Biochem Parasitol, 1994, 63(2): 299-303. |
| [29] | de Lourdes Mottier M, Prichard RK. Genetic analysis of a relationship between macrocyclic lactone and benzimidazole anthelmintic selection on Haemonchus contortus[J]. Pharmacogenet Genomics, 2008, 18(2): 129-140. |
| [30] | Silvestre A, Cabaret J. Mutation in position 167 of isotype 1 beta-tubulin gene of Trichostrongylid nematodes: role in benzimidazole resistance?[J]. Mol Biochem Parasitol, 2002, 120(2): 297-300. |
| [31] | World Health Organization. Assessing the efficacy of anthelminthic drugs against schistosomiasis and soil-transmitted helminthiases[R]. Geneva: World Health Organization, 2013::1-16. |
| [32] | National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention. Report on the national survey of important human parasitic diseases in China (2015)[M]. Beijing: People’s Medical Publishing House, 2018: 1-109. (in Chinese) |
| (中国疾病预防控制中心寄生虫病预防控制所. 2015年全国人体重点寄生虫病现状调查报告[M]. 北京: 人民卫生出版社, 2018: 1-109.) |
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