Progress in the diagnosis and treatment of childhood malaria

doi:10.3760/cma.j.issn.1007-1245.2022.12.015

Abstract

Abstract: Malaria is an infectious disease caused by plasmodium parasites, which is prevalent all over the world. According to the latest report, there were an estimated 241 million cases and 627 000 deaths globally in 2020, the African region accounted for 95% of cases and 96% of deaths; children under the age of 5 years old accounted for about 80% of all malaria deaths in the region. Microscopic examination is the gold standard for the diagnosis of malaria, and rapid antigen diagnosis can also be used as a diagnostic method. Artemisinin-based combination therapies (ACTs) are recommended by the World Health Organization as the preferred treatment for malaria. In severe malaria, efficient and rapid injection of artesunate or artemether is preferred for rescue. After the disease is improved and the patients can take food, the 3-day oral regimen of ACTs is continued. Although the malaria parasite becomes less sensitive to artemisinin in some areas, most patients can be cured by prolonged drug treatment. The global fight against malaria still has a long way to go.

Key words: Malaria, Diagnosis, Treatment, Prevention, Children

摘要： 疟疾是由人类疟原虫感染引起的传染病，在全世界普遍流行，2020年，全世界估计发生2.41亿例病例，疟疾死亡人数估计为62.7万人。非洲区域占总病例人数95%和死亡人数96%。5岁以下儿童占该地区疟疾总死亡人数约80%。镜检是疟疾诊断的金标准，抗原快速诊断方法也可作为诊断方法。以青蒿素为基础的联合治疗方法被世界卫生组织推荐为治疗疟疾的首选用药。重症疟疾首选高效快速的青蒿琥酯或蒿甲醚注射剂型进行抢救，病情好转且能进食后，续用以青蒿素为基础的联合治疗方法（artemisinin combination therapies，ACTs）口服3天方案。尽管一些地区的疟原虫对青蒿素的敏感性下降，但大多数患者通过延长药物治疗时间仍可治愈。全球防控疟疾仍任重而道远。

关键词: , 疟疾, 诊断, 治疗, 预防, 儿童

Luo Qingming, Lin Chaofeng. Progress in the diagnosis and treatment of childhood malaria[J]. International Medicine and Health Guidance News, 2022, 28(12): 1693-1699.

骆庆明, 林朝凤. 儿童疟疾诊治进展[J]. 国际医药卫生导报, 2022, 28(12): 1693-1699.

References

[1] 江载芳,申昆玲,沈颖. 诸福棠实用儿科学[M].8版.北京:人民卫生出版社,2015:1119-1124,1709.

[2] World Health Organization. World malaria report 2021[EB/OL]. https://www.who.int/publications/i/item/9789240040496.

[3] 汪天平,李石柱.热带病诊疗及防护手册[M]. 北京:人民卫生出版社,2018.

[4] World Health Organization. From 30 million to zero: China creates a malaria-free future 2019[EB/OL]. https://www.who.int/news-room/feature-stories/detail/from- 30-millionto-zero-china-creates-a-malaria-free-future.

[5] 中华人民共和国国家统计局.中国统计年鉴-2019[EB/OL]. http://www.stats.gov.cn/tjsj/ndsj/2019/indexch.htm.

[6] 蒙日朗,黄亚铭.东南亚国家疟疾流行及防治概况[J].中国热带医学,2010,10(2):244-246. DOI:10.13604/j.cnki. 46- 1064/r.2010.02.029.

[7] 黄斌,谢银彩,李景.赤道几内亚儿童疟疾的防治现状[J].临床合理用药杂志,2021,14(15):179-181. DOI:10.15887/j.cnki.13-1389/r.2021.15.065.

[8] Romay-Barja M, Jarrin I, Ncogo P, et al. Rural-urban differences in household treatment-seeking behaviour for suspected malaria in children at Bata district, Equatorial Guinea[J]. PLoS One, 2015, 10(8):e0135887. DOI: 10.1371/journal.pone.0135887.

[9] 唐克香,杨恒林.疟疾病原学检测研究进展[J].中国病原生物学杂志,2011,6(9):694-696. DOI:10.13350/j.cjpb.2011. 09.023.

[10] 营雅茹,李卫东,张滔,等.快速检测试剂条、镜检和PCR在疟疾诊断中的应用研究[J].中华疾病控制杂志,2014,18(2):163-165.

[11] 王加志,李希尚,尹授钦,等.镜检、抗原检测和核酸检测方法在疟疾诊断中的应用比较[J].热带病与寄生虫学,2020,18(1):46-48,58. DOI:10.3969/j.issn.1672-2302.2020. 01.011.

[12] Fung MS, Xiao N, Wang S, et al. Field evaluation of a PCR test for Schistosoma japonicum egg detection in low-prevalence regions of China[J]. Am J Trop Med Hyg, 2012, 87(6):1053-1058. DOI: 10.4269/ajtmh.2012.12- 0177.

[13] Mens PF, de Bes HM, Sondo P, et al. Direct blood PCR in combination with nucleic acid lateral flow immunoassay for detection of Plasmodium species in settings where malaria is endemic[J]. J Clin Microbiol, 2012, 50(11):3520-3525. DOI: 10.1128/JCM.01426-12.

[14] 顾亚萍,周华云,曾俊,等.复式PCR检测间日疟原虫和恶性疟原虫的现场应用[J].中国血吸虫病防治杂志,2012,24(3):298-302. DOI:10.3969/j.issn.1005-6661.2012.03.012.

[15] Lima NF, Bastos MS, Ferreira MU. Plasmodium vivax: reverse transcriptase real-time PCR for gametocyte detection and quantitation in clinical samples[J]. Exp Parasitol, 2012, 132(3):348-354. DOI: 10.1016/j.exppara. 2012.08.010.

[16] 青蒿的药理研究[J].新医药学杂志,1979 8(01):23-33. DOI:10.13288/j.11-2166/r.1979.01.022.

[17] 靳永刚,滕翕和,孙存普.自由基与青蒿琥酯毒性机理[J].中国药理学与毒理学杂志,1989 3(2):138-143.

[18] Ye ZG, Van Dyke K, Wimmer M. Effect of artemisinin (qinghaosu) and chloroquine on drug-sensitive and drug-resistant strains of Plasmodium falciparum malaria: use of [2,8-3H]adenosine as an alternative to [G-3H]hypoxanthine in the assessment of in vitro antimalarial activity[J]. Exp Parasitol, 1987, 64(3):418-423. DOI: 10.1016/0014-4894(87)90055-5.

[19] Gu HM, Warhurst DC, Peters W. Rapid action of Qinghaosu and related drugs on incorporation of [3H]isoleucine by Plasmodium falciparum in vitro[J]. Biochem Pharmacol, 1983, 32(17):2463-2466. DOI: 10.1016/0006-2952(83)90002-3.

[20] Li Y, Wu YL. A golden phoenix arising from the herbal nest-a review and reflection on the study of antimalarial drug Qinghaosu[J]. Front Chem China, 2010, 5(4):357-422.

[21] 汤雨晴,郑维义.抗疟疾药物的研究现状与发展[J].中国新药杂志,2019,28(8):961-966.

[22] 李雪平,杨亚明.恶性疟原虫对青蒿素类药物抗药性的研究进展[J].中国热带医学,2008,8(12):2250-2253. DOI:10.3969/j.issn.1009-9727.2008.12.107.

[23] Dondorp AM, Nosten F, Yi P, et al. Artemisinin resistance in Plasmodium falciparum malaria[J]. N Engl J Med, 2009, 361(5):455-467. DOI: 10.1056/NEJMoa0808859.

[24] Charman SA, Arbe-Barnes S, Bathurst IC, et al. Synthetic ozonide drug candidate OZ439 offers new hope for a single-dose cure of uncomplicated malaria[J]. Proc Natl Acad Sci U S A, 2011, 108(11):4400-4405. DOI: 10.1073/pnas.1015762108.

[25] Teuscher F, Gatton ML, Chen N, et al. Artemisinin‐induced dormancy in plasmodium falciparum: duration, recovery rates, and implications in treatment failure[J]. J Infect Dis, 2010, 202(9):1362-1368. DOI: 10.1086/656476.

[26] WHO Guidelines for malaria - 31 March 2022[EB/OL]. https://www.who.int/teams/global-malaria-programme/guidelines-for-malaria.

[27] 葛彬,徐闫,丁俊威,等.抗疟疾新药研发的各种策略[J].国外医药(抗生素分册),2018,39(1):1-13. DOI:10.3969/j.issn.1001-8751.2018.01.001.

[28] von Seidlein L, Dondorp A. Fighting fire with fire: mass antimalarial drug administrations in an era of antimalarial resistance[J]. Expert Rev Anti Infect Ther, 2015, 13(6):715-730. DOI: 10.1586/14787210.2015. 1031744.

[29] 郭瑞霞,李力更,付炎,等.天然药物化学史话:奎宁的发现、化学结构以及全合成[J].中草药,2014,45(19):2737-2741. DOI:10.7501/j.issn.0253-2670.2014.19.001.

[30] 中华人民共和国国家卫生和计划生育委员会. 中华人民共和国卫生行业标准:抗疟药使用规范(WS/T485-2016)[S]. 2016.

[31] Camarda G, Jirawatcharadech P, Priestley RS, et al. Antimalarial activity of primaquine operates via a two-step biochemical relay[J]. Nat Commun, 2019, 10(1):3226. DOI: 10.1038/s41467-019-11239-0.

[32] Okoromah CA, Afolabi BB. Mannitol and other osmotic diuretics as adjuncts for treating cerebral malaria[J]. Cochrane Database Syst Rev, 2004(4):CD004615. DOI: 10.1002/14651858.CD004615.pub2.

[33] Okoromah CA, Afolabi BB, Wall EC. Mannitol and other osmotic diuretics as adjuncts for treating cerebral malaria[J]. Cochrane Database Syst Rev, 2011, 2011(4):CD004615. DOI: 10.1002/14651858.CD004615.pub3.

[34] Dexamethasone in cerebral malaria[J]. N Engl J Med, 1982, 307(5):317-319. DOI: 10.1056/nejm198207293070518.

[35] Wyler DJ. Steroids are out in the treatment of cerebral malaria: what's next?[J]. J Infect Dis, 1988, 158(2):320-324. DOI: 10.1093/infdis/158.2.320.

[36] Iwagami M, Nakatsu M, Khattignavong P, et al. Heterogeneous distribution of k13 mutations in Plasmodium falciparum in Laos[J]. Malar J, 2018, 17(1):483. DOI: 10.1186/s12936-018-2625-6.

[37] Nyunt MH, Soe MT, Myint HW, et al. Clinical and molecular surveillance of artemisinin resistant falciparum malaria in Myanmar (2009-2013)[J]. Malar J, 2017, 16(1):333. DOI: 10.1186/s12936-017-1983-9.

[38] Das S, Saha B, Hati AK, et al. Evidence of artemisinin-resistant plasmodium falciparum malaria in eastern India[J]. N Engl J Med, 2018, 379(20):1962-1964. DOI: 10.1056/NEJMc1713777.

[39] Lu F, Culleton R, Zhang M, et al. Emergence of indigenous artemisinin-resistant plasmodium falciparum in Africa[J]. N Engl J Med, 2017, 376(10):991-993. DOI: 10.1056/NEJMc1612765.

[40] Amaratunga C, Lim P, Suon S, et al. Dihydroartemisinin-piperaquine resistance in Plasmodium falciparum malaria in Cambodia: a multisite prospective cohort study[J]. Lancet Infect Dis, 2016, 16(3):357-365. DOI: 10.1016/S1473-3099(15)00487-9.

[41] 罗丹,刘伟光,杨亚明.青蒿素类抗疟药的作用机制及耐药机制研究进展[J].中国医学创新,2014,11(9):131-133,134. DOI:10.3969/j.issn.1674-4985.2014.09.052.

[42] Basco LK, Ringwald P. Molecular epidemiology of malaria in Cameroon. X. Evaluation of PFMDR1 mutations as genetic markers for resistance to amino alcohols and artemisinin derivatives[J]. Am J Trop Med Hyg, 2002, 66(6):667-671. DOI: 10.4269/ajtmh.2002.66.667.

[43] Mohammed A, Ndaro A, Kalinga A, et al. Trends in chloroquine resistance marker, Pfcrt-K76T mutation ten years after chloroquine withdrawal in Tanzania[J]. Malar J, 2013, 12:415. DOI: 10.1186/1475-2875-12-415.

[44] 孙艾明,王剑,董莹,等.云南省疟疾报告病例恶性疟原虫PfKelch13基因突变与青蒿素耐药性的关联性分析[J].生物学杂志,2018,35(1):21-25. DOI:10.3969/j.issn.2095-1736. 2018.01.021.

[45] World Health Organization. Artemisinin resistance and artemisinin-based combination therapy efficacy[EB/OL]. https://www.who.int/docs/default-source/documents/publications/gmp/who-cds-gmp-2019-17-eng.pdf.

[46] World Health Organization. Malaria vaccine: WHO position paper - March 2022 [EB/OL]. https://www.who.int/publications/i/item/WER9709.