Malaria diagnosis Removing the blindfold
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Transcript of Malaria diagnosis Removing the blindfold
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
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Amexo M, Tolhurst R, Barnish G, Bates I. Malaria Misdiagnosis: effects on the poor and vulnerable. Lancet 2004; 364:1896-98
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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
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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 ….
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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 ?
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Conventional microscopy for malaria detection
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Malaria Rapid Diagnostic Tests (RDTs)
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Courtesy: Malaria Consortium
Accurate malaria diagnosis can now be accessible to all.
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(% of RDT use by month in 2007 - 2008)
Senegal RDT implementation
Courtesy Babacar Faye and Senegal MoH
Senegal malaria incidence among fever cases
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2006 Dec-07 Dec-08
% o
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Large-scale RDT introduction
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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
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RDT useACT use
Scale up of RDTs and ACTs in India M
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Source: personal communication: NMCP India, 2008
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Reported malaria cases, Zambia Livingstone District, 2004 - 2008
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Introduction of RDTs
Bednet introduction
12 month health worker follow-up Zambia 2007-8Zambia NMCC, Mal Consortium, WHO, FIND, URC
ACT
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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
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Product Testing
Rnd 1 (2008) 41 productsRnd 2 (2009) 27 productsRnd 3 (2010): 47 products
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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
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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
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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%
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20%
30%
40%
50%
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70%
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90%
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Test prep RDT reading
Package directions Job aid only Job aid + training
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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…
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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
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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
Q 4
2005
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2005
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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
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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
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Current maps of malaria incidence
www.map.ox.ac.uk2009
WHO 2009
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Polio case numbers
1988: 350,0001999: 7,1412000: 2,9792001: 483
Possible future for malaria??
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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.
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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?