Professor David Schellenberg, director of the ACT Consortium, presents at the European Congress on Tropical Medicine and International Health in Basel, Switzerland on 7 September 2015.

1. Improving malaria treatment and control through
enhanced diagnostic practice
9th European Congress in Tropical Medicine & International Health
Basel, Switzerland
Monday 7th
September 2015
David Schellenberg
Professor of Malaria & International Health
ACT Consortium Director
London School of Hygiene and Tropical Medicine
Answering key questions on malaria drug delivery 1

2. 2
Questions around ACT use
ACCESS: Poorest have worst access to malarial drugs
How can this be improved?
TARGETING: Many ACTs used by people without malaria.
Implications for ACT cost-effectiveness, drug resistance, non-malaria
case management
How can ACTs be used more efficiently?
SAFETY: Drugs may be licensed with data in ~6,000 people
Rare but important adverse events may not be detected pre-licensure
Need to consolidate safety profile eg repeat dosing, subgroups (eg HIV),
interactions (eg antiretrovirals)
QUALITY: Substandard and fake ACTs
Weak systems for assessment of drug quality in endemic countries
What is ACT?
•Artemisinin-based Combination Treatment
•The recommended treatment for uncomplicated malaria
caused by Plasmodium falciparum
What is ACT?
•Artemisinin-based Combination Treatment
•The recommended treatment for uncomplicated malaria
caused by Plasmodium falciparum

3. 3
Goal of the ACT Consortium
To develop and evaluate mechanisms to improve ACT delivery
25 projects in 10 countries, working on:
ACCESS
TARGETING
SAFETY
QUALITY
ACT Consortium 2007-2016

4. 4
Questions around ACT use
ACCESS: Poorest have worst access to malarial drugs
How can this be improved?
TARGETING: Many ACTs used by people without malaria.
Implications for ACT cost-effectiveness, drug resistance, non-malaria
case management
How can ACTs be used more efficiently?
SAFETY: Drugs may be licensed with data in ~6,000 people
Rare but important adverse events may not be detected pre-licensure
Need to consolidate safety profile eg repeat dosing, subgroups (eg HIV),
interactions (eg antiretrovirals)
QUALITY: Substandard and fake ACTs
Weak systems for assessment of drug quality in endemic countries
What is ACT?
•Artemisinin-based Combination Treatment
•The recommended treatment for uncomplicated malaria
caused by Plasmodium falciparum
What is ACT?
•Artemisinin-based Combination Treatment
•The recommended treatment for uncomplicated malaria
caused by Plasmodium falciparum
Drug Quality
11.45am - Wednesday 9th September
Singapore. Dr Harparkash Kaur

5. ACT Consortium and the broader malaria context
3 pillars:
1. Ensure universal access to malaria prevention, diagnosis and treatment.
2. Accelerate efforts towards elimination and attainment of malaria-free status.
3. Transform malaria surveillance into a core intervention.
WHO Global Technical Strategy for Malaria 2016-2030
Endorsed by 2015 World Health Assembly
Action and Investment to defeat Malaria 2016-2030 (AIM) – for a malaria-free world
Approved by Roll Back Malaria Partnership board
Concrete targets to accelerate progress towards a malaria-free world
Encourages the development of tailored country programmes

6. 6
Access to Treatment
African children <5 yr with confirmed malaria
WHO World Malaria Report 2014

7. 7
Getting ACTs to people
Every country has its own set of malaria drug delivery challenges

8. 8
The Private Sector
Formal & informal
Hospitals & clinics; (licensed) drug shops; street vendors
Most malaria treatments obtained from the private sector in
some countries
E.g. DRC 85%, Nigeria 95%
Nigeria + DRC generated 1/3 of African malaria cases in 2006

9. 9
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

10. 10
The need for targeting ACTs:
Tanzanian Health Facilities
Low prevalence (Mbeya)
Medium prevalence (Mwanza)
No diagnostic testing
Medium prevalence (Mtwara)

11. 11
A Balancing Act
ACCESS
TARGETING
Drug subsidies – e.g. Affordable Medicines
Facility for malaria (AMFm) – effectively
enhance access in private retail sector

12. 12
Getting ACT to people who need it
Appropriate diagnostic strategies are needed wherever patients
seek care

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. • 3 outpatient clinics in Tanzania.
• Patients randomly assigned blood
slide or Paracheck RDT
(Reyburn et al, BMJ January 2007)
A Role for Rapid
Diagnostic Tests?

15. Training to improve targeting of ACTs:
www.actconsortium.org/TACT
TACT trial:
Health
worker and
community
interventions
to improve
adherence to
Tanzania’s
national
guidelines
for ACT use

16. 16
TACT: Health worker and community
interventions to improve adherence to
Tanzania’s national guidelines for ACT use
Study methods:
● Randomized study to improve management of malaria
cases, and treatment of other fever cases.
● Conducted in 36 health facilities, in 3 groups:
1) RDTs and basic training only
2) RDT training, messages from senior staff, and monthly
supervision sessions
3) Same as group 2, plus community-based intervention to
modify patients’ expectations.
● Related study looked at safety of using RDTs to diagnose
and treat young children.

17. 17
Study conclusions:
● Training health workers for 2 days decreased the number of
ACT prescriptions by approximately 75%.
ACT use in RDT negative patients may reduce over time.
● Training and motivational SMS can improve prescribing
practices.
Information for patients can improve prescriber’s use of
RDTs.
● In 965 children age 3-59 months, use of RDTs did not lead to
any missed diagnoses of malaria.
TACT: Health worker and community
interventions to improve adherence to Tanzania’s
national guidelines for ACT use

18. Use of
malaria
RDTs to
improve
malaria
treatment
in the
community
in Uganda
www.actconsortium.org/RDThomemanagement
Community-based programs:

19. 19
Use of malaria RDTs to improve malaria
treatment in the community in Uganda
Study methods:
● Randomised study compared CHWs using RDT-based
diagnosis, vs symptom-based diagnosis.
● 379 CHWs in 120 communities participated. High & low
transmission settings.
● MoH researchers trained CHWs in RDT use, malaria case
management, and referral
● Community meetings to raise awareness about RDTs.

20. 20
Use of malaria RDTs to improve malaria
treatment in the community in Uganda
Study results:
● CHWs adhered to RDT results. Appropriate ACT use was
higher in villages where CHWs used RDTs, versus
symptom-based treatment:
• High transmission: 79% vs 31% (p<0.001)
• Lower transmission: 90% vs 8% (p<0.001)
● CHWs who used RDTs referred more patients to health
facilities.

21. 21
Ugandan community health workers, RDTs & ACT
Control group:
symptomatic diagnosis
Intervention group:
RDT-guided treatment
High
Transmission
Low
Transmission

22. 22
Use of malaria RDTs to improve malaria
treatment in the community in Uganda
Study conclusions:
● CHW use of RDTs can improve malaria diagnosis and help
ensure that patients receive appropriate malaria treatment.
● Community members understand that not all fever is
caused by malaria, and can accept RDT testing.
● As a result, the number of ACT treatments given can
reduce dramatically.

23. A D V E R T I S E M E N T
Poster Speed Talks
Kairo 1
1.55pm: Health facility caseload changes during the
introduction of community case management of malaria in
south-western Uganda
2.40pm: Referral from community health workers
Tomorrow – Tuesday 8th
September

24. RDTs in
drug shops
to improve
the targeting
of malaria
treatment in
Uganda
www.actconsortium.org/RDTdrugshops
Private health care sector:
Upcoming Talk – 2.15pm –
Dr Sian Clark

25. 25
Diagnostics in the Private Sector
Is it possible to incentivise the use of RDTs for patients &
shopkeepers?
Approximate prices:
●RDT $ 0.65
●ACT $ 4.00 (without subsidy)
●ACT $ 0.25 (with subsidy)
Opportunity (& challenge) to capture data
Challenge of management of RDT negative patients
Pilot implementation
projects ongoing
(UNITAID support)

26. 26
Mapping the causes of non-malaria fever
www.wwarn.org/surveyor/NMFI

27. 27
Cross-consortium analyses
Harmonised approaches, facilitated by a consortium data
repository, enable cross project, sector & country analyses:
- Explaining variation in RDT uptake and compliance with results
- Understanding RDT impact on patient care including subsequent
treatment-seeking, household costs and health outcomes
- Modelling cost-effectiveness of RDT introduction in private sector
- RDTs and malaria care in the peripheries of the Ugandan health
system - comparison of RDT introduction in public, private and
community health care settings
Upcoming Talk – 2pm –
Dr Katia Bruxvoort

28. 28
Impact of RDTs on subsequent treatment-seeking, costs & health
outcomes. Poster speed talk - 11.25am today
Mapping fever aetiologies. Poster 1.021
Explaining variation in RDT uptake & adherence to results. Poster 1.022
Kairo 1
2.10pm: Modelling cost effectiveness of RDTs in the
private for profit sector
Tomorrow – Tuesday 8th
September -

29. 29
Emerging broad findings
RDTs improve the targeting of ACTs
In all settings, fewer patients without malaria received an ACT
Wide variation in the level of improvement across settings – analyses
ongoing
Not all patients with a positive RDT receive an ACT
How to balance reduced wastage of ACTs against missed treatments?
No evidence that RDTs improve individual health outcomes
Introducing RDTs does not appear to be harmful
Introducing RDTs increases the use of anti-bacterials

30. 30
RDTs – Some considerations to
maximise impact
How to balance untreated infections with reduced ACT wastage
How to manage patients with a negative RDT?
How to assure appropriate patient referral, especially from
private retail and community sectors?
Where should RDTs be rolled out in the private retail sector?
How to incentivise appropriate behaviour of provider & client?
How to capture data from the private retail sector?
How to strengthen information systems & decision-making to
capitalise on increasingly available parasitological data?

31. Malaria prevalence in Tanzania
1980-2012
Loess regression line of 2193 survey data points assembled between 1980 and 2012
Source: Epidemiological profile of malaria and its control 2013

32. District-specific malaria risk
Tanzania 2000 and 2010

33. 33
Conclusions
RDTs can reduce ACT wastage across the health system
Need to join the dots in each country – community health workers,
private retail outlets, public health facilities – into a coherent malaria
diagnostic strategy across the health system
Rational management of non-malaria fevers: How to identify
patients who need referral for further assessment and treatment?
Communicating with Communities: need to raise awareness of
CURRENT malaria risk & create demand for appropriate treatment
Use the information generated by RDTs to inform control
Capture data, from all sectors. Target efforts where risk is highest.
Tailor control to suit the setting!

34. 34
ACCESS
TARGETING
SAFETY
QUALITY
25 projects in 10 countriesCentres for Disease Control and Prevention, USA
College of Medicine, University of Malawi, Malawi
College of Medicine, University of Nigeria, Nigeria
Dangme West District Health Directorate, Ghana
Georgia Institute of Technology, Georgia, USA
Heath Protection and Research Organisation, Afghanistan
Ifakara Health Institute, Tanzania
Infectious Disease Research Collaboration, Uganda
Karolinska Institutet, Sweden
Kilimanjaro Christian Medical Centre, (KCMC), Tanzania
Kintampo Health Research Centre, Ghana
Liverpool School of Tropical Medicine, UK
London School of Hygiene and Tropical Medicine, UK
National Institute for Medical Research, Tanzania
University of Cape Town, South Africa
University of Copenhagen, Denmark
University of Yaoundé, Cameroon
www.ACTconsortium.org
Coordinated by the London School of Hygiene and Tropical Medicine
Funded by the Bill and Melinda Gates Foundation
Answering key questions on malaria drug delivery