Prevention of the Recurrence of Anaemia in Gambian Children Following Discharge from Hospital

Abstract

BackgroundIn malaria endemic countries, children who have experienced an episode of severe anaemia are at increased risk of a recurrence of anaemia. There is a need to find ways of protecting these at risk children from malaria and chemoprevention offers a potential way of achieving this objective.MethodsDuring the 2003 and 2004 malaria transmission seasons, 1200 Gambian children with moderate or severe anaemia (Hb concentration <7 g/dL) were randomised to receive either monthly sulfadoxine-pyrimethamine (SP) or placebo until the end of the malaria transmission season in which they were enrolled, in a double-blind trial. All study subjects were treated with oral iron for 28 days and morbidity was monitored through surveillance at health centres. The primary endpoint was the proportion of children with moderate or severe anaemia at the end of the transmission season. Secondary endpoints included the incidence of clinical episodes of malaria during the surveillance period, outpatient attendances, the prevalence of parasitaemia and splenomegaly, nutritional status at the end of the malaria transmission season and compliance with the treatment regimen.ResultsThe proportions of children with a Hb concentration of <7 g/dL at the end of the malaria transmission season were similar in the two study groups, 14/464 (3.0%) in children who received at least one dose of SP and 16/471 (3.4%) in those who received placebo, prevalence ratio 0.89 (0.44,1.8) P = 0.742. The protective efficacy of SP against episodes of clinical malaria was 53% (95% CI 37%, 65%). Treatment with SP was safe and well tolerated; no serious adverse events related to SP administration were observed. Mortality following discharge from hospital was low among children who received SP or placebo (6 in the SP group and 9 in the placebo group respectively).ConclusionsIntermittent treatment with SP did not reduce the proportion of previously anaemic children with moderate or severe anaemia at the end of the malaria season, although it prevented malaria. The combination of appropriate antimalarial treatment plus one month of iron supplementation and good access to healthcare during follow-up proved effective in restoring haemoglobin to an acceptable level in the Gambian setting.Trial RegistrationClinicalTrials.gov NCT00131716

Intermittent preventive antimalarial treatment for children with anaemia

“…All included trials were conducted in malaria‐endemic areas. Three trials were conducted in low endemicity areas: two in The Gambia ( Bojang 2010 GMB ; Cox 2013 GMB ) and one in eastern Kenya ( Verhoef 2002 KEN ). Three trials were conducted in high endemicity areas: one in western Kenya ( Desai 2003 KEN ), one in southern Malawi ( Phiri 2012 MWI ) and one in western Tanzania ( Tomashek 2001 TNZ ).…”

“…The remaining trial enrolled children with Hb levels less than 7 g/dL ( Bojang 2010 GMB ). In one trial, children had severe malaria ( Phiri 2012 MWI ), two trials included children with uncomplicated malaria ( Cox 2013 GMB ; Desai 2003 KEN ), for two trials malaria was not part of the inclusion criteria ( Bojang 2010 GMB ; Tomashek 2001 TNZ ) and one trial excluded children with clinical malaria ( Verhoef 2002 KEN ). Three trials ( Bojang 2010 GMB ; Phiri 2012 MWI ; Tomashek 2001 TNZ ) recruited children that attended outpatient clinics or were admitted to hospital, while three trials recruited children from the community ( Cox 2013 GMB ; Desai 2003 KEN ; Verhoef 2002 KEN ).…”

“…In Bojang 2010 GMB only children with malaria were treated with quinine and SP or CQ and SP. Verhoef 2002 KEN was the only trial where no baseline treatment was given to children.…”

“…A small effect was seen although this disappears when we removed trials at high risk of bias from the analysis. 9 Downgraded by 1 for serious risk of bias: High risk for attrition bias for Bojang 2010 GMB and Desai 2003 KEN . 10 No serious indirectness: Three trials gave IPT (SP) monthly and one trial gave CQ weekly to anaemic children attending hospital, outpatient clinics or recruited in the community.…”

Implications of inconsistent anaemia policies for children and adolescents in Africa

“…Other trials have demonstrated increased adverse effects (27) , including increased hospital admissions (23) . Other useful measures assessed for reducing anaemia included malaria control (20,28,29) , anthelmintics (30) especially albendazole-praziquantel combinations (16) , daily micronutrients (5,31) and delayed cord clamping (32) . Food fortification with micronised Fe improved children's Fe stores but did not increase Hb levels (2,33) .…”