1DB. FIND 11 2009

Malaria diagnosis

Removing the blindfoldDavid Bell

WHO – Global Malaria Programme

LSHTMApril 2010

DB. WHO/GMP Liu Bolin

DB. WHO/GMP

Magnitude of over-diagnosis /over-treatment

Before 2000 MEDIAN PR = 36%

From 2000-2005 MEDIAN PR = 19%

Systematic review: 24 studies conducted between 1989 and 2005

in 15 different African countriesincluding 15’331 patients

Proportion of malaria among fevers highly variable: 2% to 81%

MEDIAN PR = 26%

Courtesy of: V. D’Acremont, C. Lengeler, B. Genton, Philadelphia, November 2007

DB. WHO/GMP

Amexo M, Tolhurst R, Barnish G, Bates I. Malaria Misdiagnosis: effects on the poor and vulnerable. Lancet 2004; 364:1896-98

DB. WHO/GMP

The importance of distinguishing malaria from other causes of fever

Admissions for ‘malaria’ in 10 hospitals in NE Tanzania.High mortality for wrongly-diagnosed fever

Admissions for malaria n=17,313

Severe disease n=4670 (27%)

Readable slide results n=4474 (95%)

No criteria forsevere disease n=12,643 (73%)120 deaths (1%)

Expert microscopy negativen=2412 (54%)

Deadn=142 (7%)

Aliven=1920 (93%)

Deadn=292 (12%)

Aliven=2120 (88%)

Expert microscopy positiven=2062 (46%)

Reyburn H et al. BMJ 2004

DB. WHO/GMP

Diagnostic contrasts: Malaria and other diseases

• ? TB: Treat if disease is confirmed• ? HIV: Treat if disease is confirmed• ? Influenza: Treat if disease is confirmed• ? Pneumonia: Treat if disease is confirmed (signs)• ? Typhus: Treat if disease is confirmed• ? ………

• ? Malaria: Guess, treat, and hope ….

DB. WHO/GMP

Malaria Diagnosis, WHO, 2009• Prompt parasitological confirmation by microscopy or alternatively by RDTs

is recommended in all patients suspected of malaria before treatment is started.

• Treatment solely on the basis of clinical suspicion should only be considered when a parasitological diagnosis is not accessible.

Symptom-based

Micro-scopy RDT Symptom-

basedMicro-scopy RDT

Referral Hospitals

District Hospitals

Health Centers

Private Clinics

Aid Posts/Volunteers

Private Pharmacies

Households ?

DB. WHO/GMP

Conventional microscopy for malaria detection

DB. WHO/GMP

Malaria Rapid Diagnostic Tests (RDTs)

DB. WHO/GMP

Courtesy: Malaria Consortium

Accurate malaria diagnosis can now be accessible to all.

DB. WHO/GMP

(% of RDT use by month in 2007 - 2008)

Senegal RDT implementation

Courtesy Babacar Faye and Senegal MoH

Senegal malaria incidence among fever cases

0

10

20

30

40

50

2006 Dec-07 Dec-08

% o

f fev

er

Large-scale RDT introduction

DB. WHO/GMP

Weekly Malaria Lab. Tests, 2008, Kabale District: Uganda Saving costs by treating only lab confirmed case!

Uganda, RDT implementation

Courtesy Uganda MoH, Uganda WHO office

DB. WHO/GMP

0

2

4

6

8

10

12

2003 2004 2005 2006 2007

RDT useACT use

Scale up of RDTs and ACTs in India M

illio

ns o

f kits

/dos

es

Source: personal communication: NMCP India, 2008

DB. WHO/GMP

Reported malaria cases, Zambia Livingstone District, 2004 - 2008

0

2000

4000

6000

8000

10000

12000

14000

2004

Q 1

2004

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2004

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IRS

Introduction of RDTs

Bednet introduction

12 month health worker follow-up Zambia 2007-8Zambia NMCC, Mal Consortium, WHO, FIND, URC

ACT

DB. WHO/GMP

Challenges to ensuring access to accurate RDT-based diagnosis

• Sensitivity 20% to 99% in published studies

• Stability – Recommended storage temperature often inappropriate for rural

health clinic in tropics (e.g. <30°C)

• User safety – Blood safety (gloves, sharps disposal, HIV risk)

• Programmatic– Managing negative results (non-malaria fever patients)

– Logistics

– Monitoring

– Treatment ignoring diagnostic results

DB. WHO/GMP WHO, FIND, TDR, US CDC

Product Testing

Rnd 1 (2008) 41 productsRnd 2 (2009) 27 productsRnd 3 (2010): 47 products

DB. WHO/GMP

HTD

CDC

UL IPB RITMIPC

AMI

IHRDC

Collection and testing siteSpecimen characterization

IPM

DMR

CIDEIM

IMT

KEMRIEHNRI

UCAD

Regional lot-testing site

2006: 41 lots

2007: 81 lots

2008: 167 lots 2009: 196 lots (?15% of public sector procurement)

2010: +++

Lot Testing

DB. WHO/GMP

Community-level monitoring of RDT quality

Now: Compare routinely with microscopy (often difficult)

Future: Positive Control Wells• Under development by FIND, WHO, and partners

• Field implementation trials planned

Dried antigen

Water addedContents placed on

RDT

1 2 3 4 5 6 7 8 9 10

Antigen concentration

Antigen typesFuture lot-testing panels

DB. WHO/GMP

Taking heath-worker training seriously - Zambia

Zambia MoH, URC, WHO, TDR, FIND, Malaria Consortium www.wpro.who.int/sites/rdt,

Suite of products:Job-aidTraining manualPhotographic result guideProficiency tests

61%

72%

81%86%

90%96%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Test prep RDT reading

Package directions Job aid only Job aid + training

DB. WHO/GMP

Managing fever, not malaria

Febrile patient

RDT / microscopy

Manage in community? review? Antibiotics? Other

Non-malaria

Anti-malarial medicine

Malaria

Severe symptoms

Refer

Not severe

Anti-malarial medicine

~20% ~80%

Can of worms…

DB. WHO/GMP

Procurement of RDTs

Training, drugs / supplies for non-malarial fever

Community educationTraining and supervisionMonitoring accuracy in fieldLot-testing and laboratory monitoringProcurement of gloves, sharps disposal containers etc

Transport and storage

Minimum standard for funding a diagnostic programme?

Need to build programmes, not just fund procurement

DB. WHO/GMP

Where do we go after we are successful?… a larger can of worms…

Reported malaria cases, Zambia Livingstone District, 2004 - 2008

0

2000

4000

6000

8000

10000

12000

14000

2004

Q 1

2004

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2004

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2004

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2005

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2005

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2007

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2008

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2008

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2008

Q 4

IRS

Introduction of RDTs

Bednet introduction

Successful intervention10 cases per month.

Malaria now down from 1st to 16th district health priority….other disease priorities are more urgent

But the mosquitoes and the people are still there…

We have the tools to identify and manage malaria as a common disease

We need new tools and strategies to manage malaria as a rare disease

DB. WHO/GMP

New diagnostic strategies to achieve and maintain elimination

Finding and eliminating hidden parasite reservoirs

Malaria LAMP

Detects 1 parasite/µL

Potential for district / clinic level use

Find and treat malaria ‘carriers’

Serology

Screen large populations for signs of recent malaria transmission

DB. WHO/GMP

Current maps of malaria incidence

www.map.ox.ac.uk2009

WHO 2009

DB. WHO/GMP

Polio case numbers

1988: 350,0001999: 7,1412000: 2,9792001: 483

Possible future for malaria??

DB. WHO/GMP

Summary: Parasite-based diagnosis and ACT

If no parasite-based diagnosis:– Most recipients of ACT will not have malaria – Patients with non-malarial febrile illness will receive wrong or late

treatment – Malaria incidence rates will be unavailable

• (Poor resource allocation, poor planning, no elimination)

However, delaying ACT raises malaria mortality:– Improving access to ACT is essential, should not be delayed

Diagnosis needs to catch up to treatment.

DB. WHO/GMP

Thank you

Are we victims of a history?If malaria arose for the first time today…. would we consider routinely sending children home with 3 days of anti-malarial drugs when we know they probably have another, potentially fatal, illness?