Diadier Diallo TEG symposium, 29 th March 2012
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Transcript of Diadier Diallo TEG symposium, 29 th March 2012
SEASONAL MALARIA CHEMOPREVENTION (SMC) FOR MALARIA CONTROL IN SUB-SAHARAN AFRICA: FROM
RESEARCH TO POLICY
Diadier Diallo TEG symposium, 29th March 2012
From IPT to SMC
Intermittent preventive treatment of malaria tried in older children (IPTc) (Cisse et al; 2006) 367;659-667
Intermittent preventive treatment
of malaria initially recommended for
prevention of malaria in
pregnancy (IPTp) and then in infants
(IPTi) using SP
IPTc renamed Seasonal Malaria Chemoprevention (SMC)
What is Seasonal Malaria Chemoprevention (SMC)?
Intermittent administration of full treatment courses of an antimalarial medicine during the malaria transmission season to prevent malarial illness with the objective of maintaining therapeutic antimalarial drug concentrations in the blood throughout the period of greatest malarial risk (WHO TEG, 2011)
Seasonal malaria chemoprevention
• Several studies using different drug regimens were carried out between 2002-2011
• A Task Force was set up in 2008 to gather evidence on – Efficacy, Safety, Delivery mechanisms of SMC
• The Task Force commissioned a review of SMC study results
Meta-Analysis endpoint definitions
• Clinical malaria with any parasitaemia• Severe malaria (WHO definition) • Moderate anaemia prevalence (Hb < 8g/dL or PCV<
25%)• Serious adverse events / adverse events• Parasite prevalence• Drug resistance including resistance to SP
14 studies identified and 8 met inclusion criteria
Impact of monthly SMC (any drug regimen) on clinical malaria during the intervention period
NOTE: Weights are from random effects analysis
D+L Overall (I-squared = 89.9%, p = 0.000)
ID
Kweku, 2008, AS+AQ
I-V Overall
Study
Zongo, unpub SPAQ
Konate, 2011, SP+AQ
Cisse, 2006, SP+AS
Bojang, 2010, DHA+PQ
Bojang, 2010, SP+PQ
Zongo, unpub DHAPQ
Sesay, 2011, SP+AQ
Dicko, 2011, SP+AQ
Bojang, 2010, SP+AQ
0.17 (0.13, 0.22)
Ratio (95% CI)
0.25 (0.18, 0.35)
0.20 (0.19, 0.22)
Rate
0.13 (0.10, 0.15)
0.29 (0.26, 0.33)
0.17 (0.14, 0.21)
0.13 (0.06, 0.29)
0.07 (0.03, 0.20)
0.15 (0.13, 0.18)
0.51 (0.05, 5.59)
0.17 (0.14, 0.20)
0.07 (0.03, 0.21)
100.00
(D+L)
12.32
Weight
13.76
14.49
13.58
6.72
4.98
13.88
1.25
14.03
4.98
%
1.02 .2 .5 1.5 6
Rate Ratio
Protective efficacy against uncomplicated clinical malaria = 83% (95% CI: 78% , 87%)
No protection
Impact of SMC on severe malaria, anaemia and all-cause mortality
Protective effectEndpoints PE (95%CI)
Severe malaria 76 % (46% to 89%)
Anaemia Hb,8g/dl or PCV < 25% 20% (- 5% to 38%)
All-cause mortality (all regimens) 18% (-69% to 61%)
All-cause mortality (SP+AQ only) 34% (- 73% to 75%)
LLIN + Placebo LLIN + SMCNo. of cases
Incidence rate (95% CI)
No. of cases
Incidence rate (95% CI)
PE(95%CI)
P value
Malaria (parasitaemia > 5000)
1656 2.38 (2.27-2.50) 458 0.61 (0.56-0.67) 75 (72-77)
<0.001
Severe malaria
220.002
(0.001 – 0.003) 40.0004
(0.0001 – 0.0011)82
(48–94) 0.002
All-cause hospital admissions
450.056
(0.042– 0.075) 270.033
(0.023 – 0.049)41
(5–63) 0.03
Efficacy of SMC in context of high ITN coverage
Konaté et al, 2011 and Dicko et al, 2011
Safety: Adverse Events (AEs)
• More than 900, 000 courses administered to more than 190, 000 children
• Most common AEs was vomiting, associated with SP+PQ, DHA+PQ and SP+AQ
• No drug-related serious adverse events identified– No evidence of severe skin reactions or blood
dyscrasias
Effect of SMC on clinical malaria in the high transmission season post intervention
Pooled analyses from 7 studies
IRRs = 1.08 (95%CI: 1.03 – 1.12)
In the context of high coverage with ITNs
IRRs = 1.10 (95%CI: 1.03 – 1.17)
No increase in severe malaria, all-cause hospital admissions or deaths
Delivery of SMC, Basse, The Gambia Delivery methods
Village health workers
RCH trekking teams
% Coverage all courses 74% 48%% adherence days 2 & 3 of AQ
98% 98%
Clinical malaria attacks/child months
1.2 2.8
Cost per cases $ 1.6 $ 3.5
(Bojang et al. PloS Med 2011)8:e1000408)
Coverage - large scale SMC study in Senegal
12
2008 (N=1018)
2009 (N=3226)
2010 (N=909)
No. of treatment
courses
Coverage % (95%CI)
Coverage % (95%CI)
Coverage % (95%CI)
02.3
(1.2, 3.5)5.3
(4.2 , 6.5)3.3
(1.7, 4.9)
10.8
(0.2, 1.4)1.5
(1.0 , 2.0)1.5
(-0.1, 0.5)
23.0
(1.2, 4.7)3.0
(1.8 , 4.2)0.5
(0.1, 1.0)
392.4
(90.2, 94.6)84.3
(81.8 , 86.8)89.7
(82.4, 97.0)
Missing1.5
(0.7, 2.4)5.9
(4.4 , 7.3)6.2
(-1.1, 13.6)
Breakdown excluding research incentives
Drug administration (CHWs)
Supervision
SMC DrugsResearch participation incentives
Total financial cost in 2010, in Senegal•Total Financial Cost: US$ 233,713
•Courses of treatment administered: 471,282•Children under 10: 175,000 •Coverage: >90%•Cost per course $0.5
13
(Greenwood et al., Trends Parasitol 2011, 27, 477-480)
Studies in The Gambia and Ghana
15
Areas potentially suitable for SMC
Low SP resistance
High SP resistanceAlternative drugs needed
Sahel 25millions children under 5
East/Southern Africa 14 millions children under 5
Potential impact of SMC on the burden of malaria
Sahel and sub-Sahel S & E Africa
Cases averted (millions) Malaria deaths averted (1000s)
Policy process
• Meeting in Dakar in October 2008
• Meeting with the WHO policy group in July 2010
• Presentation SMC data to the WHO Technical Expert Group (TEG) in May 2011.
• Further information needed, but this should delay implementation
• TEG recommended implementation of SMC
Policy process
• The WHO MPAC reviewed recommendation in Feb 2012
• WHO likely to formulate policy recommendation on SMC
• A working group meeting convened to review and finalise implementation field guide
• Countries are preparing implementation plan, anticipating a policy recommendation
Conclusions
• Substantial protective effect against clinical malaria• SMC is safe and generally well tolerated• SMC delivery is feasible with high coverage• SMC likely to be cost effective in areas where it is suited• Millions of episodes can be averted a year • Strong evidence to support the adoption of SMC for
malaria control in areas of seasonal malaria transmission
WHO is likely to recommend SMC for areas of seasonal malaria transmission
Bill & Melinda Gates Foundation
LSHTM Brian Greenwood Paul MilliganAnne WilsonDaniel ChandramohanSimon CousensGeoff TargettMatt CairnsAzra GhaniAmit Bhasin
All the investigators The SMC working group
IPTc TaskforceOumar Gaye (Chair)Kalifa Bojang Badara Cissé Lesong ContehDiadier Diallo (Secretary)Ogobara DoumboMalang FofanaBocar KouyatéLaurent MoyengaSeth Owusu-AgyeiKlénon Traore
Acknowledgements