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. 2018 Dec 12;18(1):650.
doi: 10.1186/s12879-018-3556-0.

Safety and effectiveness of antimalarial therapy in sickle cell disease: a systematic review and network meta-analysis

Augustina Frimpong  1   2   3 , Laty Gaye Thiam  1 , Benjamin Arko-Boham  4 , Ewurama Dedea Ampadu Owusu  4   5 , George O Adjei  6   7
Affiliations

Safety and effectiveness of antimalarial therapy in sickle cell disease: a systematic review and network meta-analysis

Augustina Frimpong et al. BMC Infect Dis. .

Abstract

Background: About 80% of all reported sickle cell disease (SCD) cases in children anually are recorded in Africa. Although malaria is considered a major cause of death in SCD children, there is limited data on the safety and effectiveness of the available antimalarial drugs used for prophylaxis. Also, previous systematic reviews have not provided quantitative measures of preventive effectiveness. The purpose of this research was to conduct a systematic review and meta-analysis of the available literature to determine the safety and effectiveness of antimalarial chemoprophylaxis used in SCD patients.

Methods: We searched in PubMed, Medline, CINAHL, POPLine and Cochrane library, for the period spanning January 1990 to April 2018. We considered randomized or quasi-randomized controlled trials comparing any antimalarial chemoprophylaxis to, 1) other antimalarial chemoprophylaxis, 2) placebo or 3) no intervention, in SCD patients. Studies comparing at least two treatment arms, for a minimum duration of three months, with no restriction on the number of patients per arm were reviewed. The data were extracted and expressed as odds ratios. Direct pairwise comparisons were performed using fixed effect models and the heterogeneity assessed using the I-square.

Results: Six qualified studies that highlighted the importance of antimalarial chemoprophylaxis in SCD children were identified. In total, seven different interventions (Chloroquine, Mefloquine, Mefloquine artesunate, Proguanil, Pyrimethamine, Sulfadoxine-pyrimethamine, Sulfadoxine-pyrimethamine amodiaquine) were evaluated in 912 children with SCD. Overall, the meta-analysis showed that antimalarial chemoprophylaxis provided protection against parasitemia and clinical malaria episodes in children with SCD. Nevertheless, the risk of hospitalization (OR = 0.72, 95% CI = 0.267-1.959; I2 = 0.0%), blood transfusion (OR = 0.83, 95% CI = 0.542-1.280; I2 = 29.733%), vaso-occlusive crisis (OR = 19, 95% CI = 1.713-2.792; I2 = 93.637%), and mortality (OR = 0.511, 95% CI = 0.189-1.384; I2 = 0.0%) did not differ between the intervention and placebo groups.

Conclusion: The data shows that antimalarial prophylaxis reduces the incidence of clinical malaria in children with SCD. However, there was no difference between the occurrence of adverse events in children who received placebo and those who received prophylaxis. This creates an urgent need to assess the efficacy of new antimalarial drug regimens as potential prophylactic agents in SCD patients.

Systematic review registration: PROSPERO (CRD42016052514).

Keywords: Adverse events; Chemoprophylaxis; Effectiveness; Malaria; Safety; Sickle cell disease.

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Conflict of interest statement

Authors’ information

AF and LGT are supported by a Ph.D. fellowship from a World Bank African Centres of Excellence Grant (ACE02-WACCBIP: Awandare); AF is also supported by the International Development Research Center grant from the African Institute for Mathematical Sciences, Ghana, a recipient of the L’Oreal-UNESCO for Women in Science Grant, the Carnegie Corporation of New York and the University of Ghana BanGA Ph.D. Grant.

Ethics approval and consent to participate

Not applicable.

Consent for publication

The authors have read and agreed to the content of this manuscript and its publication upon acceptance.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
PRISMA flow chart for the systematic review of antimalarial drugs used for preventing malaria in sickle cell disease (SCD) patients
Fig. 2
Fig. 2
Network diagram of interventions included in the analysis. A network of eligible comparisons for the efficacy of the various treatments. Lines represent the presence of direct comparison trials. The width of the lines represent the number of participants included in the intervention groups
Fig. 3
Fig. 3
Summary plot showing the effectiveness of the chemoprophylaxis with placebo as a reference. Antimalarial drugs were compared to placebo with the risk of developing malaria. Each single drug was represented as a square. The square area denotes the contribution of the drug to the meta-analysis. Horizontal line denotes the odds ratio and the confidence interval. The diamond represents the combined odds ratio with confidence interval. Odds ratios lower than 1 favour interventions and 95% CI values (Lower limit and Upper limit) comprised between 0 and 1 is associated with a significant difference
Fig. 4
Fig. 4
Forest plots showing the commonly reported adverse-events related to the antimalaria chemoprophylaxis in SCD patients. Results are shown for (a) hospitalization, (b) blood transfusion, (c) vaso-occlusive crisis and (d) mortality with placebo as a reference. The square area denotes the contribution of the drug to the meta-analysis. Horizontal line denotes the odds ratio together with the confidence intervals. The diamond represents the combined odds ratio with its confidence interval. Odd Ratios lower than 1 favour interventions and 95% CI values (Lower limit and Upper limit) comprised between 0 and 1 is associated with a significant difference
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