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