Improving malaria treatment and control through enhanced diagnostic practice9th European Congress in Tropical Medicine & International HealthBasel, SwitzerlandMonday 7th September 2015

David SchellenbergProfessor of Malaria & International HealthACT Consortium DirectorLondon School of Hygiene and Tropical Medicine

Answering key questions on malaria drug delivery 1

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Questions around ACT useACCESS: Poorest have worst access to malarial drugsHow can this be improved?

TARGETING: Many ACTs used by people without malaria. Implications for ACT cost-effectiveness, drug resistance, non-malaria case managementHow 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-licensureNeed to consolidate safety profile eg repeat dosing, subgroups (eg HIV), interactions (eg antiretrovirals)

QUALITY: Substandard and fake ACTsWeak 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

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Goal of the ACT ConsortiumTo develop and evaluate mechanisms to improve ACT delivery

25 projects in 10 countries, working on:

ACCESS

TARGETING

SAFETY

QUALITY

ACT Consortium 2007-2016

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Questions around ACT useACCESS: Poorest have worst access to malarial drugsHow can this be improved?

TARGETING: Many ACTs used by people without malaria. Implications for ACT cost-effectiveness, drug resistance, non-malaria case managementHow 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-licensureNeed to consolidate safety profile eg repeat dosing, subgroups (eg HIV), interactions (eg antiretrovirals)

QUALITY: Substandard and fake ACTsWeak 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

Drug Quality

11.45am - Wednesday 9th September

Singapore. Dr Harparkash Kaur

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 worldApproved by Roll Back Malaria Partnership board

Concrete targets to accelerate progress towards a malaria-free worldEncourages the development of tailored country programmes

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Access to Treatment African children <5 yr with confirmed malaria

WHO World Malaria Report 2014

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Getting ACTs to people

Every country has its own set of malaria drug delivery challenges

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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

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Targeting of ACTs

Private retail sector, TanzaniaBriggs 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

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The need for targeting ACTs: Tanzanian Health Facilities

Low prevalence (Mbeya)

Medium prevalence (Mwanza)

No diagnostic testing

Medium prevalence (Mtwara)

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A Balancing Act

ACCESS

TARGETING

Drug subsidies – e.g. Affordable Medicines Facility for malaria (AMFm) – effectively enhance access in private retail sector

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Getting ACT to people who need it

Appropriate diagnostic strategies are needed wherever patients seek care

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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 cureLDH – negative ~2 days after cure

• 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?

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

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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 only2) RDT training, messages from senior staff, and monthly

supervision sessions3) 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.

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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

Use of malaria RDTs to improve malaria

treatment in the

community in Uganda

www.actconsortium.org/RDThomemanagement

Community-based programs:

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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.

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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.

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Ugandan community health workers, RDTs & ACT

Control group: symptomatic diagnosis

Intervention group: RDT-guided treatment

High Transmission

Low Transmission

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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.

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

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

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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)

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Mapping the causes of non-malaria fever

www.wwarn.org/surveyor/NMFI

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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

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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 12.10pm: Modelling cost effectiveness of RDTs in the private for profit sector

Tomorrow – Tuesday 8th September -

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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 ACTHow to balance reduced wastage of ACTs against missed treatments?

No evidence that RDTs improve individual health outcomesIntroducing RDTs does not appear to be harmful

Introducing RDTs increases the use of anti-bacterials

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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?

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

District-specific malaria riskTanzania 2000 and 2010

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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!

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ACCESS

TARGETING

SAFETY

QUALITY

25 projects in 10 countries

Centres 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 MedicineFunded by the Bill and Melinda Gates Foundation

Answering key questions on malaria drug delivery