Malar J. 2021 Dec 24;20(1):483. doi: 10.1186/s12936-021-04016-2.
In vivo efficacy of anti-malarial drugs against clinical Plasmodium vivax malaria in Ethiopia: a systematic review and meta-analysis.
Malaria journal
Tsige Ketema, Ketema Bacha, Kefelegn Getahun, Quique Bassat
Affiliations
Affiliations
- Department of Biology, College of Natural Sciences, Jimma University, Jimma, Ethiopia. [email protected].
- ISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, Spain. [email protected].
- Department of Biology, College of Natural Sciences, Jimma University, Jimma, Ethiopia.
- Department of Geography and Environmental Studies, College of Social Sciences and Humanity, Jimma University, Jimma, Ethiopia.
- ISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, Spain.
- Catalan Institution for Research and Advanced Studies, ICREA, Pg. Lluís Companys 23, 08010, Barcelona, Spain.
- Centro de Investigação Em Saúde de Manhiça (CISM), Maputo, Mozambique.
- Pediatrics Department, Hospital Sant Joan de Déu, Universitat de Barcelona, Esplugues, Barcelona, Spain.
- Consorcio de Investigación Biomédica en Red de Epidemiología Y Salud Pública (CIBERESP), Madrid, Spain.
PMID: 34952581
DOI: 10.1186/s12936-021-04016-2
Abstract
BACKGROUND: Ethiopia is one of the few countries in Africa where Plasmodium vivax commonly co-exists with Plasmodium falciparum, and which accounts for ~ 40% of the total number of malaria infections in the country. Regardless of the growing evidence over many decades of decreasing sensitivity of this parasite to different anti-malarial drugs, there has been no comprehensive attempt made to systematically review and meta-analyse the efficacy of different anti-malarial drugs against P. vivax in the country. However, outlining the efficacy of available anti-malarial drugs against this parasite is essential to guide recommendations for the optimal therapeutic strategy to use in clinical practice. The aim of this study was to synthesize evidence on the efficacy of anti-malarial drugs against clinical P. vivax malaria in Ethiopia.
METHODS: All potentially relevant, peer-reviewed articles accessible in PubMed, Scopus, Web of Science, and Clinical Trial.gov electronic databases were retrieved using a search strategy combining keywords and related database-specific subject terms. Randomized controlled trials (RCTs) and non-randomized trials aiming to investigate the efficacy of anti-malarial drugs against P. vivax were included in the review. Data were analysed using Review Manager Software. Cochrane Q (χ
RESULTS: Out of 1294 identified citations, 14 articles that presented data on 29 treatment options were included in the analysis. These studies enrolled 2144 clinical vivax malaria patients. The pooled estimate of in vivo efficacy of anti-malarial drugs against vivax malaria in Ethiopia was 97.91% (95% CI: 97.29-98.52%), with significant heterogeneity (I
CONCLUSION: The overall efficacy of anti-malarial drugs evaluated for the treatment of vivax malaria in Ethiopia was generally high, although there was wide-ranging degree of efficacy, which was affected by the treatment options, duration of follow-up, transmission intensity, and the confirmation procedures for recurrent parasitaemia. Regardless of evidence of sporadic efficacy reduction reported in the country, chloroquine (CQ), the first-line regimen in Ethiopia, remained highly efficacious, supporting its continuous utilization for confirmed P. vivax mono-infections. The addition of primaquine (PQ) to CQ is recommended, as this is the only approved way to provide radical cure, and thus ensure sustained efficacy and longer protection against P. vivax. Continuous surveillance of the efficacy of anti-malarial drugs and clinical trials to allow robust conclusions remains necessary to proactively act against possible emergence and spread of drug-resistant P. vivax in Ethiopia.
© 2021. The Author(s).
Keywords: Anti-malarial drug; Artemether-lumefantrine; Chloroquine; Efficacy; Ethiopia; In vivo; Plasmodium vivax; Primaquine
References
- Battle KE, Lucas TCD, Nguyen M, Howes RE, Nandi AK, Twohig KA, et al. Mapping the global endemicity and clinical burden of Plasmodium vivax, 2000–17: a spatial and temporal modelling study. Lancet. 2019;394:332–43. - PubMed
- Howes RE, Battle KE, Mendis KN, Smith DL, Cibulskis RE, Baird JK, et al. Global epidemiology of Plasmodium vivax. Am J Trop Med Hyg. 2016;95(Suppl 6):15–34. - PubMed
- WHO. World Malaria Report 2019. Geneva, World Health Organization; 2019. https://www.who.int/publications/i/item/world-malaria-report-2019 - PubMed
- Culleton R, Ndounga M, Zeyrek FY, Coban C, Casimiro PN, Takeo S, et al. Evidence for the transmission of Plasmodium vivax in the Republic of the Congo. West Central Africa J Infect Dis. 2009;200:1465–9. - PubMed
- Ménard D, Barnadas C, Bouchier C, Henry-Halldin C, Gray LR, Ratsimbasoa A, et al. Plasmodium vivax clinical malaria is commonly observed in Duffy-negative Malagasy people. Proc Natl Acad Sci USA. 2010;107:5967–71. - PubMed
- WHO. New opportunities to prevent P. vivax malaria relapse. Geneva, World Health Organization; 2019. https://www.who.int/malaria/news/2019/new-opportunities-to-prevent-vivax-malaria-relapse/en/ - PubMed
- Alonso P, Noor AM. The global fight against malaria is at crossroads. Lancet. 2017;390:2532–4. - PubMed
- Bhatt S, Weiss DJ, Cameron E, Bisanzio D, Mappin B, Dalrymple U, et al. The effect of malaria control on Plasmodium falciparum in Africa between 2000 & 2015. Nature. 2015;526:207–11. - PubMed
- Tulu AN, Webber RH, Schellenberg JA, Bradley DJ. Failure of chloroquine treatment for malaria in the highlands of Ethiopia. Trans R Soc Trop Med Hyg. 1996;90:556–7. - PubMed
- Federal Ministry of Health of Ethiopia. Malaria Diagnosis and Treatment Guidelines for Health Workers. Addis Ababa, Ethiopia; 2004. - PubMed
- Price RN, Seidlein LV, Valecha N, Nosten F, Baird JK, White NJ. Global extent of chloroquine-resistant Plasmodium vivax: a systematic review and meta-analysis. Lancet Infect Dis. 2014;14:982–91. - PubMed
- Anstey NM, Douglas NM, Poespoprodjo JR, Price RN. Plasmodium vivax: clinical spectrum, risk factors and pathogenesis. Adv Parasitol. 2012;80:151–201. - PubMed
- Markus MB. Malaria: origin of the term “hypnozoite.” J Hist Biol. 2011;44:781–6. - PubMed
- Commons RJ, Simpson JA, Watson J, White NJ, Price RN. Estimating the proportion of Plasmodium vivax recurrences caused by relapse: a systematic review and meta-analysis. Am J Trop Med Hyg. 2020;103:1094–9. - PubMed
- Engel, N., Ghergu, C., Matin, M.A. Kibria MG, Thriemer K, Price RN, et al. Implementing radical cure diagnostics for malaria: user perspectives on G6PD testing in Bangladesh. Malar J. 2021;20:217 - PubMed
- Baird JK. Primaquine toxicity forestalls effective therapeutic management of the endemic malarias. Int J Parasitol. 2012;42:1049–54. - PubMed
- Baird JK. Tafenoquine for travelers' malaria: evidence, rationale and recommendations. J Travel Med. 2018; 25:tay110 - PubMed
- Baro B, Deroost K, Raiol T, Brito M, Almeida ACG, de Menezes-Neto A, et al. Plasmodium vivax gametocytes in the bone marrow of an acute malaria patient and changes in the erythroid miRNA profile. PLoS Negl Trop Dis. 2017;11:e0005365. - PubMed
- Elizalde-Torrent A, Val F, Azevedo ICC, Ferreira LCL, Fernández-Becerra C, Del Portillo HA, et al. Sudden spleen rupture in a Plasmodium vivax-infected patient undergoing malaria treatment. Malar J. 2018;17:79. - PubMed
- WHO. Control and elimination of Plasmodium vivax malaria: a technical brief. Geneva. World Health Organization, 2015. - PubMed
- Markus MB. Malaria eradication and the hidden parasite reservoir. Trends Parasitol. 2017;33:492–5. - PubMed
- Teka H, Petros B, Yamuah L, Tesfaye G, Elhassan I, Muchohi S, et al. Chloroquine-resistant Plasmodium vivax malaria in Debre Zeit. Ethiopia Malar J. 2008;7:220. - PubMed
- Ketema T, Getahun K, Bacha K. Therapeutic efficacy of chloroquine for treatment of Plasmodium vivax malaria cases in Halaba district. South Ethiopia Parasit Vectors. 2011;4:46. - PubMed
- Beyene HB, Beyene MB, Ebstie YA, Desalegn Z. Efficacy of chloroquine for the treatment of vivax malaria in Northwest Ethiopia. PLoS One. 2016;11:e0161483. - PubMed
- Hwang J, Alemayehu BH, Reithinger R, Tekleyohannes SG, Takele Teshi, Birhanu SG, et al. In vivo efficacy of artemether-lumefantrine and chloroquine against Plasmodium vivax: a randomized open label trial in central Ethiopia. PLoS One. 2013;8:e63433. - PubMed
- Assefa M, Eshetu T, Biruksew A. Therapeutic efficacy of chloroquine for the treatment of Plasmodium vivax malaria among outpatients at Hossana Health Care Centre, southern Ethiopia. Malar J. 2015;14:458. - PubMed
- Shumbej T, Jemal A, Worku A, Bekele F, Weldesenbet H. Therapeutic efficacy of chloroquine for treatment of Plasmodium vivax malaria cases in Guragae zone southern Central Ethiopia. BMC Infect Dis. 2019;19:413. - PubMed
- Yeshiwondim AK, Tekle AH, Dengela DO, Yohannes AM, Teklehaimanot A. Therapeutic efficacy of chloroquine and chloroquine plus primaquine for the treatment of Plasmodium vivax in Ethiopia. Acta Trop. 2010;113:105–13. - PubMed
- Yohannes AM, Teklehaimanot A, Bergqvist Y, Ringwald P. Confirmed vivax resistance to chloroquine and effectiveness of artemether-lumefantrine for the treatment of vivax malaria in Ethiopia. Am J Trop Med Hyg. 2011;84:137–40. - PubMed
- Abreha T, Hwang J, Thriemer K, Tadesse Y, Girma S, Melaku Z, et al. Comparison of artemether-lumefantrine and chloroquine with and without primaquine for the treatment of Plasmodium vivax infection in Ethiopia: a randomized controlled trial. PLoS Med. 2017;14:e1002299. - PubMed
- Ketema T, Bacha K, Del Portillo H A, Bassat Q. Plasmodium vivax epidemiology and in vivo antimalarial efficacy studies in Ethiopia: a systematic review and meta-analysis. PROSPERO 2020 CRD42020201761. Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020201761 - PubMed
- Leonardo R. PICO: model for clinical questions. Evid Based Med Pract. 2018;3:115. - PubMed
- WHO. Methods for surveillance of antimalarial drug efficacy. Geneva. World Health Organization, 2009. Available from: https://www.who.int/malaria/publications/atoz/9789241597531/en/ . - PubMed
- Baird JK. Chloroquine resistance in Plasmodium vivax. Antimicrob Agents Chemother. 2004;48:4075–83. - PubMed
- Federal Ministry of Health of Ethiopia. Ethiopia Malaria Elimination Strategic Plan: 2021–2025: towards a malaria-free Ethiopia. Addis Ababa, Ethiopia, 2021. - PubMed
- Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al. (Eds). Cochrane Handbook for Systematic Reviews of Interventions version 6.2. Cochrane, 2021. Available from www.training.cochrane.org/handbook . - PubMed
- Ketema T, Bacha K, Birhanu T, Petros B. Chloroquine-resistant Plasmodium vivax malaria in Serbo town, Jimma zone, south-west Ethiopia. Malar J. 2009;8:177. - PubMed
- Getachew S, Thriemer K, Auburn S, Abera A, Gadisa E, Aseffa A, et al. Chloroquine efficacy for Plasmodium vivax malaria treatment in southern Ethiopia. Malar J. 2015;140:525. - PubMed
- Kanche ZZ, Sulaiman S, Woldie M, Yesuf EA. Therapeutic efficacy of chloroquine in Plasmodium vivax at health centers in Jimma Town. South-West Ethiopia J Health Med Nursing. 2016;23:13–9. - PubMed
- Seifu S, Zeynudin A, Zemene E, Suleman S, Biruksew A. Therapeutic efficacy of chloroquine for the treatment of Plasmodium vivax malaria among outpatients at Shawa Robit Health Care Centre. North-East Ethiopia Acta Trop. 2017;171:44–51. - PubMed
- Yeshanew S, Dagne A, Taye B. Efficacy study of chloroquine to Plasmodium vivax malaria in Darimu and Bure Districts. Southwest Ethiopia Infect Drug Resist. 2021;14:795–803. - PubMed
- Karunajeewa HA, Mueller I, Senn M, Lin E, Law I, Gomorrai PS, et al. A trial of combination antimalarial therapies in children from Papua New Guinea. N Engl J Med. 2008;359:2545–57. - PubMed
- Chu CS, White NJ. Management of relapsing Plasmodium vivax malaria. Expert Rev Anti Infect Ther. 2016;4:885–900. - PubMed
- Howes RE, Battle KE, Mendis KN, Smith DL, Cibulskis RE, Baird JK, et al. Global epidemiology of Plasmodium vivax. Am J Trop Med Hyg. 2016;95(6 Suppl):15–34. - PubMed
- File T, Dinka H, Golassa L. A retrospective analysis on the transmission of Plasmodium falciparum and Plasmodium vivax: the case of Adama City, East Shoa Zone, Oromia. Ethiopia Malar J. 2019;18:193. - PubMed
- Abossie A, Yohanes T, Nedu A, Tafesse W, Damitie M. Prevalence of malaria and associated risk factors among febrile children under five years: a cross-sectional study in Arba Minch Zuria District. South Ethiopia Infect Drug Resist. 2020;13:363–72. - PubMed
- Hassen J, Dinka H. Retrospective analysis of urban malaria cases due to Plasmodium falciparum and Plasmodium vivax: the case of Batu town, Oromia, Ethiopia. Heliyon, 2020;6:e03616. - PubMed
- Hastings I. Malaria control and the evolution of drug resistance: an intriguing link. Trends in Parasitol. 2003;19:70–3. - PubMed
- Hastings I, Watkins W. Intensity of malaria transmission and the evolution of drug resistance. Acta Trop. 2005;94:218–29. - PubMed
- Lefèvre G, Thomsen MS. Clinical pharmacokinetics of artemether and lumefantrine (Riamet®). Clin Drug Investig. 1999;18:467–80. - PubMed
- Mekonnen SK, Aseffa A, Berhe N, Teklehaymanot T, Clouse RM, Gebru T, et al. Return of chloroquine-sensitive Plasmodium falciparum parasites and emergence of chloroquine-resistant Plasmodium vivax in Ethiopia. Malar J. 2014;13:244. - PubMed
- Golassa, L., Erko, B., Baliraine, F.N. Aseffa A, Swedberg G. Polymorphisms in chloroquine resistance-associated genes in Plasmodium vivax in Ethiopia. Malar J. 2015;14:164. - PubMed
- Heuchert A, Abduselam N, Zeynudin A, Eshetu T, Löscher T, Wieser A, et al. Molecular markers of anti-malarial drug resistance in southwest Ethiopia over time: regional surveillance from 2006 to 2013. Malar J. 2015;14:208. - PubMed
- Lo E, Hemming-Schroeder E, Yewhalaw D, Nguyen J, Kebede E, Zemene E, et al. Transmission dynamics of co-endemic Plasmodium vivax and P. falciparum in Ethiopia and prevalence of antimalarial resistant genotypes. PLoS Negl Trop Dis. 2017;11:e0005806. - PubMed
- Auburn S, Getachew S, Pearson RD, Amato R, Miotto O, Trimarsanto H, et al. Genomic analysis of Plasmodium vivax in Southern Ethiopia reveals selective pressures in multiple parasite mechanisms. J Infect Dis. 2019;220:1738–49. - PubMed
- Mueller I, Galinski MR, Baird JK, Carlton JM, Kochar DK, Alonso PL, et al. Key gaps in the knowledge of Plasmodium vivax, a neglected human malaria parasite. Lancet Infect Dis. 2009;9:555–66. - PubMed
- Fernando D, Rodrigo C, Rajapakse S. Primaquine in vivax malaria: an update and review on management issues. Malar J. 2011;10:351. - PubMed
- John GK, Douglas NM, von Seidlein L, Nosten F, Baird JK, White WJ, et al. Primaquine radical cure of Plasmodium vivax: a critical review of the literature. Malar J. 2012;11:280. - PubMed
- Cotter C, Sturrock HJW, Hsiang MS, Liu J, Phillips AA, Hwang J, et al. The changing epidemiology of malaria elimination: new strategies for new challenges. Lancet. 2013;382:900–11. - PubMed
- White NJ. Determinants of relapse periodicity in Plasmodium vivax malaria. Malar J. 2011;10:297. - PubMed
- Juliano JJ, Taylor SM, Meshnick SR. Polymerase chain reaction adjustment in antimalarial trials: molecular malarkey? J Infect Dis. 2009;200:5–7. - PubMed
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