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Risk of drug resistance in Plasmodium falciparum malaria therapy—a systematic review and meta-analysis

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Abstract

Plasmodium falciparum is responsible for the vast majority of the morbidity and mortality associated with malaria infection globally. Although a number of studies have reported the emergence of drug resistance in different therapies for P. falciparum infection, the degree of the drug resistance in different antimalarials is still unclear. This research investigated the risk of drug resistance in the therapies with different medications based on meta-analyses. Relevant original randomized control trials (RCTs) were searched in all available electronic databases. Pooled relative risks (RRs) with 95% confidence intervals (95% CIs) were used to evaluate the risk of drug resistance resulting from different treatments. Seventy-eight studies were included in the meta-analysis to compare drug resistance in the treatment of P. falciparum infections and yielded the following results: chloroquine (CQ) > sulfadoxine-pyrimethamine (SP) (RR = 3.67, p < 0.001 ), mefloquine (MQ) < SP (RR = 0.26, p < 0.001), artesunate + sulfadoxine-pyrimethamine (AS + SP) > artemether + lumefantrine (AL) (RR = 2.94, p < 0.001), dihydroartemisinin + piperaquine (DHA + PQ) < AL (RR = 0.7, p < 0.05), and non-artemisinin-based combination therapies (NACTs) > artemisinin-based combination therapies (ACTs) (RR = 1.93, p < 0.001); no significant difference was found in amodiaquine (AQ) vs. SP, AS + AQ vs. AS + SP, AS + AQ vs. AL, or AS + MQ vs. AL. These results presented a global view for the current status of antimalarial drug resistance and provided a guidance for choice of antimalarials for efficient treatment and prolonging the life span of the current effective antimalarial drugs.

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Acknowledgements

The authors are grateful to the participants in this study and the anonymous reviewers and editors for their comments and valuable inputs.

Authors’ contributions

LJZ searched literatures and extracted data, performed meta-analysis, and wrote and submitted the manuscript; JX and HXW suggested in data analysis and revision for the manuscript; XJL suggested in malaria therapy; HJP conceived the research and wrote the manuscript.

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Authors and Affiliations

  1. Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Disease Research, and Key Laboratory of Prevention and Control for Emerging Infectious Diseases of Guangdong Higher Institutes, School of Public Health, Southern Medical University, Guangzhou, Guangdong Province, 510515, China

    Li-Juan Zhou, Jing Xia, Hai-Xia Wei & Hong-Juan Peng

  2. Nanfang Hospital, Southern Medical University, #1838 North Guangzhou Avenue, Guangzhou, Guangdong, 510515, People’s Republic of China

    Xiao-Jun Liu

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  1. Li-Juan Zhou
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Correspondence to Hong-Juan Peng.

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Funding support

This work was supported by the funding of the National Natural Science Foundation of China (No. 81271866, 81572012), the Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (2014), the Guangdong Provincial Natural Science Foundation Key Project (2016A030311025),and the Guangzhou health and medical collaborative innovation major special project(201604020011) to HJP.

Electronic supplementary material

Fig. S1.

Forest plot of the RCTs on CQ versus SP for the comparison of the likelihood of drug resistance emergence (GIF 68 kb)

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Fig. S2.

Forest plot of the RCTs on MQ versus SP for the comparison of the likelihood of drug resistance emergence (GIF 28 kb)

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Fig. S3.

Forest plot of the RCTs on AQ versus SP for the comparison of the likelihood of drug resistance emergence (GIF 55 kb)

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Fig. S4.

Forest plot of the RCTs on NACTs versus ACTs for the comparison of the likelihood of drug resistance emergence (GIF 71 kb)

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Fig. S5.

Forest plot of the RCTs on AS+AQ versus AS+SP for the comparison of the likelihood of drug resistance emergence (GIF 38 kb)

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Fig. S6.

Forest plot of the RCTs on AS+AQ versus AL for the comparison of the likelihood of drug resistance emergence (GIF 79 kb)

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Fig. S7.

Forest plot of the RCTs on AS+SP versus AL for the comparison of the likelihood of drug resistance emergence (GIF 30 kb)

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Fig. S8.

Forest plot of the RCTs on DHA+PQ versus AL for the comparison of the likelihood of drug resistance emergence (GIF 42 kb)

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Fig. S9.

Forest plot of the RCTs on AS+MQ versus AL for the comparison of the likelihood of drug resistance emergence (GIF 36 kb)

High Resolution Image (TIFF 1327 kb)

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Zhou, LJ., Xia, J., Wei, HX. et al. Risk of drug resistance in Plasmodium falciparum malaria therapy—a systematic review and meta-analysis. Parasitol Res 116, 781–788 (2017). https://doi.org/10.1007/s00436-016-5353-2

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