EVALUATION OF EFFICACY AND SAFETY OF ARTEMISININ DERIVATIVES COMPARISON WITH QUININE IN PAEDIATRIC POPULATION FOR TREATMENT OF SEVERE MALARIA: A META-ANALYSIS APPROACH
Abstract
Artemisinin and its derivatives such as artesunate, arteether and artemether are the primary and effective treatment of choice as per WHO malaria treatment guideline for the treatment of severe malaria although various endemic countries are using quinine for the treatment of severe malaria. The objective of this meta-analysis was to evaluate the efficacy and safety of artemisinin and its derivatives compared with quinine as parenteral antimalarial therapy for treating severe malaria in children. From the year 1990 to the year 2015, studies were identified using database searches, citation searches of selected articles. The electronic databases searched engines: Pubmed, Web of Science, Global Health, Medline & Cochrane review of Journals up to April 2015. We selected published randomized controlled clinical trials (RCTs) information comparing artemisinin derivatives with quinine and route of administration was either intravenous or intramuscular for treatment of severe malaria in paediatric population as per WHO malaria treatment guideline, any gender, age group up to 15 years of children who were diagnosed with confirmed malaria by RDT or slide test. The primary outcome was efficacy in terms of parasite clearance time (PCT) and fever clearance time (FCT) in paediatrics population. The secondary outcome was the mortality, coma resolution time (CRT) and neurological sequelae at the time of discharge in the paediatric population. We assessed identified articles on the basis of clinical trial eligibility, the risk of bias and extracted data as per objective of this research for the desired outcomes. We measured 95% confidence interval by the using of REVMAN software version 5.3 for meta-analysis and summarized the collected data on the basis of characteristics of inclusion criteria of articles such as risk ratio (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes. We included total 17 RCTs, enrolling 7220 paediatric patients who were suffering from severe or complicated malaria and these trials were conducted in various countries in the world. Artemisinin derivatives showed mean PCT (MD -8.53 hours, 95% CI -9.44 to -7.62) and mean FCT (MD -9.42 hours, 95% CI -11.12 to -7.71) shorter and statistically significant (P<0.00001) as compared with quinine therapy. We evaluated secondary outcomes mortality, mean coma resolution time (CRT) and the risk of neurological sequelae at the time of discharge in paediatric malaria patients which was observed; (RR 0.82, 95% CI 0.72 to 0.93; 17 trials, 7220 participants, P=0.002), (MD -5.37 hours, 95% CI -7.70 to -3.05; nine trials, 591 participants, P<0.00001) and (RR 1.07, 95% CI 0.89 to 1.28; nine trials, 5939 participants, P=0.49), respectively. This meta-analysis of RCT addresses the evidence for various aspects in the treatment of severe malaria in the paediatric population although limitation of availability of published information in studies furthermore research on paediatric malaria population is required to overcome from challenges drug resistance, patient compliance and less adverse effect.
Keywords:
Artesunate, Arteether, Artemether, Antimalarial, Children, MalariaDOI
https://doi.org/10.25004/IJPSDR.2018.100206References
2. Krause PJ. Malaria (Plasmodium). In: Behrman RE, Kliegman RM, Jenson HB, editors. Nelson Textbook of Pediatrics. 18th ed. Philadelphia, PA: WB Saunders; 2007:1477–1485.
3. Sharma A, Khanduri U. How benign is benign tertian malaria? J Vector Borne Dis. 2009; 46(2):141–144.
4. Islam N, Qamruddin K. Unusual complications in benign tertian malaria. Trop Geogr Med. 1995; 47(3):141–143.
5. Dhingra N, Jha P, Sharma V P, Cohen A A, Jotkar R M et al. Adult and child malaria mortality in India: a nationally representative mortality survey: The Lancet.2010.
6. White NJ. The treatment of malaria. N Engl J Med. 1996; 335:800–806.
7. Yen LM, Dao LM, Day NP. Role of quinine in the high mortality of intramuscular injection tetanus. Lancet. 1994;344:786–877.
8. Pasvol G. The treatment of complicated and severe malaria. Br. Med. Bull. 2006;75-76:29–47.
9. Guidelines for the treatment of malaria. Third Edition. World Health Organization, 2015.
10. Guidelines for diagnosis and treatment of malaria in India.
11. Infectious Diseases Chapter, Indian Academy of Pediatrics. Management of malaria in children: Update 2008. Indian Pediatr 2008; 45: 731-735.
12. Dondorp AM, Fanello CI, Hendriksen L, Gomes E, Seni A, Chhaganlal K, et al. Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial. Lancet 2010; 376: 1647–57.
13. Mohanty AK, Rath BK, Mohanty R, Samal AK, Mishra K. Randomized control trial of quinine and artesunate in complicated malaria. Indian J Pediatr 2004; 71: 291-295.
14. Phuong CXT, Bethell DB, Phuong PT, Mai TTT, Thuy TTN, Ha NTT, et al. Comparison of artemisinin suppositories, intramuscular artesunate and intravenous quinine for the treatment of severe childhood malaria. Trans R Soc Trop Med Hyg 1997; 91: 335-342.
15. Adam I, Idris HM, Mohamed-Ali AA, Aelbasit, Elbashir MI. Comparison of intramuscular artemether and intravenous quinine in the treatment of Sudanese children with severe falciparum malaria. East African Medical Journal 2002;79 (12):621–5.
16. Aguwa CN, Ukwe CV, Adibe MO. A comparative study of quinine and artemether in the treatment of severe malaria in Nigerian children. Tropical Journal of Pharmaceutical Research 2010;9(1):11–7.
17. Huda SN, Shahab T, Ali SM, Afzal K, Khan HM. A comparative clinical trial of artemether and quinine in children with severe malaria. Indian Pediatr 2003; 40: 939-945.
18. Minta D, Sissoko M, Sidibe I, Dolo A, Poudiougou B, Dembele M, et al. Efficacy and safety of artemether in the treatment of severe and complicated malaria in Mali. Mali Médical 2005; 20(1-2):28–32.
19. Murphy S, English M, Waruriu C, Mwangi I, Amoukoye E, Crawley J, et al. An open randomised trial of artemether versus quinine in the treatment of cerebral malaria in African children. Trans R Soc Trop Med Hyg 1996; 90: 298-301.
20. Ojuawo A, Adegboye AR, Oyewalw O. Clinical response and parasite clearance in childhood cerebral malaria: A comparison between intramuscular artemether and intravenous quinine. East Afr Med J 1998; 75: 450-452.
21. Olumese PE, Bjorkman A, Gbadegesin RA, Adeyemo AA, Walker O. Comparative efficacy of intramuscular artemether and intravenous quinine in Nigerian children with cerebral malaria. Acta Tropica 1999; 73: 231-236.
22. Osonuga OA, Osonuga AA, Osonuga IO, Osonuga A. Comparison of Coma Resolution Time in the Course of Treating Children with Severe Falciparum Malaria with Quinine and Artemether. World Journal of Medical Sciences 2011;6(2):42–45.
23. Satti GM, Elhassan SH, Ibrahim SA. The efficacy of artemether versus quinine in the treatment of cerebral malaria. Journal of the Egyptian Society of Parasitology 2002; 32(2):611–23.
24. Taylor TE, Wills BA, Courval JM, Molyneux ME. Intramuscular artemether vs intravenous quinine: An open, randomized trial in Malawian children with cerebral malaria. Trop Med Int Health 1998; 3: 3–8.
25. Van Hensbroek MB, Onyiorah E, Jaffar S. A trial of artemether or quinine in children with cerebral malaria. N Engl JMed 1996; 335: 69-75.
26. Walker O, Salako LA, Omukhodion SI, Sowunmi A. An open randomized comparative study of intramuscular artemether and intravenous quinine in cerebral malaria in children. Transactions of the Royal Society of Tropical Medicine and Hygiene 1993;87(5):564–6.
27. Moyou-Somo R, Tietche F, Ondoa M, Kouemeni LE, Ekoe T, Mbonda E, et al. Clinical trial of beta arteether versus quinine for the treatment of cerebral malaria in children in Yaounde, Cameroon. Am J Trop Med Hyg 2001; 64: 229-232.
28. Thuma PE, Bhat GJ, Mabeza GF, Osborne C, Biemba G, Shakankale GM, et al. A randomized controlled trial of artemotil (beta-arteether) in Zambian children with cerebral malaria. Am J Trop Med Hyg 2000; 62: 524-529.
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