Abstract
BackgroundAbout 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.MethodsWe 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.ResultsSix 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.ConclusionThe 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 registrationPROSPERO (CRD42016052514).
Highlights
Sickle cell disease (SCD) is a group of autosomal recessive inherited disorders caused by a single nucleotide substitution (T > A) in the β-globin gene
A linkage exists between the presence of sickle haemoglobin (HbS) and protection from malaria in the heterozygous state [4], malaria is a frequent cause of hospitalization and poor outcome among children with sickle cell disease (SCD) in endemic areas [5, 6], and malaria is associated with a higher mortality in hospitalized SCD patients compared to hospitalized non-SCD patients [7,8,9]
A total of 912 SCD patients were included in the six studies, and the following seven chemoprophylactic regimens [(a) Proguanil (PG); (b) Sulphadoxine-Pyrimethamine (SP); (c) Mefloquine (MQ); (d) Chloroquine (CQ); (e) Pyrimethamine (PM); (f) Mefloquine-Artesunate (MQAS); and (g) Sulphadoxine-Pyrimethamine-Amodiaquine (SPAQ)] were evaluated in the meta-analysis
Summary
Sickle cell disease (SCD) is a group of autosomal recessive inherited disorders caused by a single nucleotide substitution (T > A) in the β-globin gene. SCD accounts for 5–19% mortality in children in sub-Saharan Africa, where the highest frequency of homozygous SCD occurs [2]. SCD-related mortality occurs mostly in undiagnosed infants in sub-Saharan Africa, and is predominantly attributed to infections, including malaria [3]. Prophylaxis against malaria is important in SCD patients, as antimalarial chemoprophylaxis has been shown to be beneficial in SCD patients, reducing parasitaemia and anaemia, and the requirement for blood transfusion [10,11,12]. 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. 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
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