Presentation by David Schellenberg Director, ACT Consortium Professor of Malaria & International Health at London School of Hygiene & Tropical Medicine

1. Prof David Schellenberg
London School of Hygiene & Tropical Medicine

2. Prof David Schellenberg
London School of Hygiene & Tropical Medicine

3. Prof David Schellenberg
London School of Hygiene & Tropical Medicine

4. The ACT Consortium
Goal: Develop and evaluate mechanisms to improve ACT delivery
ACCESS
TARGETING
SAFETY
QUALITY
Formative research, cluster
randomised trials, cohort and
descriptive studies, impact
evaluations, economic and
anthropological studiesACT Consortium 2007-2016
25 projects
10 countries
20+ institutions
What is ACT?
•Artemisinin-based Combination Treatment
•The recommended treatment for uncomplicated malaria
caused by Plasmodium falciparum

5. ACT now for a malaria-free world
https://vimeo.com/109480993

6. 6
Access to ACT
among African children <5 years with confirmed malaria
WHO World Malaria Report 2014

7. Getting ACTs to people who need them
Appropriate diagnostic strategies are needed
wherever patients seek care

8. The Private Sector
Pharmacies, shops, mobile street vendors
Most malaria treatments are obtained from the
private sector in some countries
• Eg DRC 85%, Nigeria 95%
• Nigeria + DRC had 1/3 of all African malaria cases in
2006
Subsidies for ACTs can enhance access
• E.g. novel financing mechanisms such as the
Affordable Medicines Facility for malaria (AMFm)

9. A Balancing Act
ACCESS
TARGETING

10. 10
Targeting of ACTs
Private retail sector, Tanzania
Briggs M et al (2014) PLoS ONE 9(4): e94074.
Fever patients attending private retail outlets in Tanzania
• 70% of those infected did not get ACTs
• 80% of those receiving ACTs were not infected

11. 11
The need for targeting ACTs:
Tanzanian Health Facilities
Low prevalence (Mbeya)
Medium prevalence (Mwanza)
No diagnostic testing
Medium prevalence (Mtwara)

12. 12
The Goal
www.actconsortium.org/VennGeneratorTool

13. 13
Rapid Diagnostic Tests (RDTs)
Point of care diagnostic
No laboratory or electricity
needed, minimum training
Based on antigen capture:
2 main types
• HRP-2 – persists (weeks)
after cure
• LDH – negative ~2 days
after cure

14. Access & Targeting Studies
1. UGANDA
Public health facilities
(part of HF ‘enhancement’ trial)
2.+3. UGANDA
HBMF
Drug shops
(comparing with no RDT)
4. TANZANIA
Public health facilities
(Observing MoH scale-up)
7. ZANZIBAR
Public health facilities
(observational)
6. AFGHANISTAN
Public health facilities
(IRT & cluster trials of RDT
vs standard care)
9. TANZANIA
Public health facilities
(+peer group training;
patient intervention)
8. GHANA
Public health facilities
(observational safety &
health outcomes)
15. GHANA
Public health facilities
(IRT RDT vs standard)
5a. CAMEROON
Public health facilities
(enhanced training)
5b. NIGERIA
Public & Private
(enhanced training;
community intervention)
IRT = Individually Randomised Trial

15. Ugandan community health workers,
RDTs & ACTs
Control group:
Symptom-based diagnosis
Intervention group:
RDT-guided treatment
High
Transmission
Low
Transmission
no ACT

16. 16
Antibiotic prescription by RDT result
RDTs available
Positive Negative Not tested
*
*
*
0
10
20
30
40
50
60
70
80
90
100
Percentage
RDT arms
Positive
0
10
20
30
40
50
60
70
80
90
100
Percentage
RDT arms
Negative
0
10
20
30
40
50
60
70
80
90
100
Percentage
RDT arms
Not tested

17. Mapping causes of non-malaria febrile illness
in malaria-endemic areas
www.wwarn.org/surveyor/NMFI
A collaboration with WWARN/Oxford and several other partners

18. 18
ACT Consortium research:
Our 25 studies in 10 countries address ACT:
Access
Targeting
Safety
Quality

19. Drug Safety
Individual trials are often insufficiently powered to detect
rare side effects
With widespread programmatic
implementation of ACTs,
need to consolidate safety profiles
ACT Consortium studies
sought to address questions on:
•High-risk groups including children subjected to repeat dosing
•Safety in people with HIV, including those on anti-retrovirals

20. Data Capture Tools
• Formative research to develop a range of
tools
– Non-clinician & clinicians
– Active follow-up & spontaneous reports
– Adults & children

21. Data flow in drug safety repository
Signal Detection
(Data Mining
Tool)
Centralised Safety
Database
ADR repository
Additional Participant
data
I
D
SAEs/AEs
Data
Entry
Additional
denominator
data
Liverpool SG/CSP
DSR
Liverpool
Send electronically or by
fax on continuous basis
Descriptive
analysis & signal
investigation/
confirmation
Batch Data Upload at
pre-defined intervals
ACT
Ex
Com
m
Assessment for
causality,
severity, coding
(MedDRA, WHO)
Research
sites (direct
or via PV co-
ordinator)
Conversion of
trial files to
compatible file
format
Data output
(emerging
signals)
DSMB
s PIs
Reports
Dissemination
DSMB/
Sponsor
No new safety concerns have been identified
Safety repository is available for wider use
www.actconsortium.org/drugsafetydatabase

22. Future work on drug safety
Online resource for pharmacovigilance work in collaboration with
The Global Health Network (TGHN)
•Link to safety reports and tools from ACT Consortium and other sites
with open-access material relevant for global community
•Invite experts for interviews, topical discussions
•Survey membership to inform
further resources
Website launch planned for May 2016
• Review training opportunities
& identify eLearning needs,
for collaborative
development

23. 23
ACT Consortium research:
Our 25 studies in 10 countries address ACT:
Access
Targeting
Safety
Quality

24. Fake antimalarials?
Can health professionals and patients assume that the medicines that
they are prescribing and taking are of good quality?

25. 10,000 packets of ACTs
3 independent laboratories
6 endemic countries
RESULTS
Country (date of sampling) Brands Falsified Substandard
Rwanda (2008) 1 0 found 6.2%
Cambodia (2010) 21 0 found 31.3%
Ghana-Kintampo (2011) 31 0 found 37.0%
Tanzania (2010) 37 0 found 12.0%
Tanzania (2011) 46 0 found 2.2%
Nigeria-Enugu Metropolis (2013) 131 1.2% 6.6%
Nigeria-Ilorin city (2013) 77 0.8% 7.7%
Equatorial Guinea-Bioko Island (2014) 142 7.4% 1.6%

26. Distribution of Active Pharmaceutical
Ingredients (APIs) in ACTs in Tanzania
Compared with stated amount,
one or more APIs outside
85-115% for 12.1% samples
(30.6% outside 90-110%)
%ofantimalarials
Active Pharmaceutical Ingredient (%)
Am J Trop Med Hyg 2015: doi:10.4269/ajtmh.14-0544

28. Process Evaluations in Operational Research
If a strategy
doesn’t work,
make sure the
evaluation can
show where it
broke down.
If it does work,
identify
components
critical to
success!
A
B L A C K
B O X

29. 29
RESOURCES
●Resources in English, French and Portuguese
www.actconsortium.org

30. 30
Please send
questions & comments to
#actdiagnosis
@ACTconsortium
debora.miranda@lshtm.ac.uk

31. Our multidisciplinary teams developed, piloted, delivered &
evaluated training resources…
…now available to those responsible for developing health
communication & training about malaria diagnosis & treatment

32. Listening to Your Audience:
Qualitative Research
in Malaria Interventions
Dr Clare Chandler