Seasonal Malaria Chemoprevention: “Rebound” Implementation Workshop on Seasonal Malaria Chemoprevention 13-15 February 2017, Ouagadougou, Burkina Faso Dr. Peter OLUMESE, Global Malaria Programme WHO, Geneva, Switzerland.

DEFINITION OF ‘REBOUND’ IN RELATION TO MALARIA CONTROL An increase in the incidence of malaria in the period after a period of effective malaria control has been achieved (by any means) above that which would have occurred if the intervention had not taken place. Malaria INTERVENTION Intervention group Control group x Rebound

Definition SMC is the intermittent administration of full treatment courses of an antimalarial medicine during the malaria season to prevent malaria illness and deaths objective is to maintain therapeutic drug concentrations in the blood throughout the period of greatest malaria risk. Children aged 3 - 59 months, Amodiaquine plus sulfadoxine- pyrimethamine (AQ+SP) Monthly administration  Given from the start of the transmission season Maximum of four doses per season

Evidence (Expected benefits)* Prevents approximately 75% of all malaria episodes Prevents approximately 75% of severe malaria episodes May result in a decrease in child mortality (1 fewer per 1000) Probably reduces the incidence of moderately severe anaemia (19 fewer per 1000) Does not result in an increase in clinical malaria in the following malaria transmission season after one year of administration Serious adverse events have not been reported and are probably rare *Based on results from 7 studies on SMC conducted in areas of highly seasonal transmission of malaria using AQ+SP monthly for up to 4 months during the transmission season in children less than 5 years of age

REBOUND AFTER ONE YEAR OF SMC Burkina Faso 3.84 [3,67,4.02] 3.45 [3.29;3.62] 0.064 [0.046,0.089] 0.068 [0.050.0.094] IRR 1.12 [1.04-1.20] IRR 0.94 [0.60.1.47] Incidence of clinical malaria Incidence of hospital admissions Previous SMC Previous control Previous SMC Previous control Mali 1.87 [1.76,1.99] 1.73 [1.62,1.85] 0.014 [0.00p,0.022] 0.009 [0.005,0.016] IRR 1.09 [0.99,1.21] IRR 1.54 [1.77.3.11] (Konate et al. Plos One 2011;6:e23391. Dicko et al. PloS One 2011;6:e23390)

Status of on-going SMC Implementation Sub-national implementation rather than full country Fully sensitive parasites assumed clinical parasitological failure rate (28 days): Adherence and system compliance Coverage Programmatic implementation – districts, other interventions delivered at same time

Rebound – “Caveats” When considering ‘rebound ‘ it is important to differentiate between malaria of different severities and between different types of severe malaria. It is important to compare numbers of cases in intervention and ‘rebound’ periods, and not just percentage changes in incidence, as incidence may have changed during the period of the intervention, for example decreasing with increasing age.

SEASONAL CHEMOPROPHYLAXIS IN GAMBIAN CHILDREN Percentage reduction Overall deaths Malaria deaths Malaria episodes Parasit- aemia Spleno- megaly (Greenwood et al., Lancet 1988; i:1121; Menon et al. TRSTMH 1990;84:768)

INCIDENCE OF CLINICAL MALARIA IN CHILDREN AGED 5-6 YEARS AFTER RECEIPT OF SEASONAL CHEMOPROPHYLAXIS FOR A VARIABLE NUMBER OF YEARS P<0.001 ns ns ns 2 3 4 5 YEARS OF PROPHYLAXIS (Greenwood et al. TRSTMH 1995; 89:629-33)

MORTALITY IN GAMBIAN CHILDREN AFTER PROPHYLAXIS Prophylaxis stopped (Greenwood et al. TRSTHM 1995; 89: 629-33)

REBOUND AFTER CHEMOPROPHYLAXIS IN TANZANIAN CHILDREN Control Clinical malaria Weekly prophylaxis with Daraprim 2-12 months Severe malaria Severe anaemia (Aponte et al. Plos Med 2007; 4:e242)

REBOUND AFTER CHEMOPROPHYLAXIS IN TANZANIAN CHILDREN Clinical malaria Control Chemoprophylaxis Severe malaria Weekly prophylaxis with Daraprim 2-12 months Severe anaemia (Aponte et al. Plos Med 2007; 4:e242)

CONCLUSIONS Rebound is inevitable after a period of effective malaria control that is terminated unless the transmission intensity has fallen in a sustained way during the follow-up period. In nearly all circumstances the benefit from the period of effective intervention will outweigh the deleterious impact of rebound. The potential for rebound to occur needs to be recognised and managed with steps taken to alleviate its impact, for example by ensuring enhanced use of other control measures during the at risk period such as LLIN.

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