Transcript LSHTM

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 initially
recommended for
prevention of
malaria in
pregnancy (IPTp)
and then in infants
(IPTi) using SP
Intermittent preventive
treatment of malaria tried in
older children (IPTc) (Cisse et
al; 2006) 367;659-667
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
No protection
%
Study
Rate
Weight
ID
Ratio (95% CI)
(D+L)
Kweku, 2008, AS+AQ
0.25 (0.18, 0.35)
12.32
Cisse, 2006, SP+AS
0.17 (0.14, 0.21)
13.58
Bojang, 2010, DHA+PQ
0.13 (0.06, 0.29)
6.72
Bojang, 2010, SP+PQ
0.07 (0.03, 0.20)
4.98
Bojang, 2010, SP+AQ
0.07 (0.03, 0.21)
4.98
Dicko, 2011, SP+AQ
0.17 (0.14, 0.20)
14.03
Konate, 2011, SP+AQ
0.29 (0.26, 0.33)
14.49
Sesay, 2011, SP+AQ
0.51 (0.05, 5.59)
1.25
Zongo, unpub SPAQ
0.13 (0.10, 0.15)
13.76
Zongo, unpub DHAPQ
0.15 (0.13, 0.18)
13.88
D+L Overall (I-squared = 89.9%, p = 0.000)
0.17 (0.13, 0.22)
100.00
I-V Overall
0.20 (0.19, 0.22)
NOTE: Weights are from random effects analysis
.02
.2
.5
Rate Ratio
1
1.5
6
Protective efficacy against uncomplicated clinical malaria
= 83% (95% CI: 78% , 87%)
Impact of SMC on severe malaria,
anaemia and all-cause mortality
Protective effect
Endpoints
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%)
Efficacy of SMC in context of high ITN
coverage
LLIN + Placebo
No. of Incidence rate
cases
(95% CI)
Malaria
1656
(parasitaemia
> 5000)
Severe
malaria
All-cause
hospital
admissions
2.38 (2.27-2.50)
22
0.002
(0.001 – 0.003)
45
0.056
(0.042– 0.075)
LLIN + SMC
No. of Incidence rate
cases
(95% CI)
PE
(95%CI)
P value
<0.001
458
0.61 (0.56-0.67)
75
(72-77)
4
0.0004
(0.0001 – 0.0011)
82
(48–94)
0.002
27
0.033
(0.023 – 0.049)
41
(5–63)
0.03
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
% Coverage all courses
% adherence days 2 & 3
of AQ
Clinical malaria
attacks/child months
Cost per cases
Village health
workers
RCH trekking
teams
74%
98%
48%
98%
1.2
2.8
$ 1.6
$ 3.5
(Bojang et al. PloS Med 2011)8:e1000408)
Coverage - large scale SMC study
in Senegal
No. of
treatment
courses
0
1
2
3
Missing
2008
(N=1018)
Coverage
% (95%CI)
2009
(N=3226)
Coverage
% (95%CI)
2010
(N=909)
Coverage
% (95%CI)
2.3
(1.2, 3.5)
0.8
(0.2, 1.4)
3.0
(1.2, 4.7)
92.4
(90.2, 94.6)
1.5
(0.7, 2.4)
5.3
(4.2 , 6.5)
1.5
(1.0 , 2.0)
3.0
(1.8 , 4.2)
84.3
(81.8 , 86.8)
5.9
(4.4 , 7.3)
3.3
(1.7, 4.9)
1.5
(-0.1, 0.5)
0.5
(0.1, 1.0)
89.7
(82.4, 97.0)
6.2
(-1.1, 13.6)
12
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
0.8%
Breakdown excluding
research incentives
1.0%
3.1%
0.7%
0.5%
0.4%
Drug ddministration
(CHWs)
Research participation
incentives
Cost IPTc Drugs (SP+AQ)
Supervision
Supplies
6.3%
Training of CHWs
12%
Supervision
Drug
administration
(CHWs) 34%
SMC Drugs
Research
19%
participation
incentives
22%
Meetings - evaluation &
planning
Training of ICPs
Sensitisation
Drugs for side effects
Drug transport/supply
13
chain
Studies in The Gambia
and Ghana
(Greenwood et al., Trends Parasitol
2011, 27, 477-480)
Areas potentially suitable for SMC
Sahel 25millions
children under 5
Low SP resistance
East/Southern Africa 14
millions children under 5
High SP resistance
Alternative drugs needed
15
Potential impact of SMC on the
burden of malaria
Cases averted (millions)
Malaria deaths averted (1000s)
80
All endemic areas
Malaria cases averted (millions)
9
Incidence > 0.1
8
Incidence > 0.2
7
6
5
4
3
2
1
0
Malaria deaths averted (thousands)
10
All endemic areas
70
Incidence > 0.1
60
Incidence > 0.2
50
40
30
20
10
0
Sahel & sub-Sahel
S & E Africa
Fixed CFR
Rowe et al
Sahel and sub-Sahel
Fixed CFR
Rowe et al
S & E Africa
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
Acknowledgements
IPTc Taskforce
LSHTM
Oumar Gaye (Chair)
Kalifa Bojang
Badara Cissé
Lesong Conteh
Diadier Diallo (Secretary)
Ogobara Doumbo
Malang Fofana
Bocar Kouyaté
Laurent Moyenga
Seth Owusu-Agyei
Klénon Traore
Brian Greenwood
Paul Milligan
Anne Wilson
Daniel Chandramohan
Simon Cousens
Geoff Targett
Matt Cairns
Azra Ghani
Amit Bhasin
All the investigators
The SMC working group
Bill & Melinda Gates Foundation