Malaria diagnosis
Removing the blindfold
David Bell
WHO – Global Malaria Programme
LSHTM
April 2010
1
DB. FIND 11 2009
DB. WHO/GMP
Liu Bolin
Magnitude of over-diagnosis /over-treatment
Systematic review: 24 studies
conducted between 1989 and 2005
in 15 different African countries
including 15’331 patients
Proportion of malaria among fevers highly variable:
2% to 81%
MEDIAN PR = 26%
Before 2000
MEDIAN PR = 36%
From 2000-2005
MEDIAN PR = 19%
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
No criteria for
severe disease
n=12,643 (73%)
120 deaths (1%)
Severe disease n=4670 (27%)
Readable slide results n=4474 (95%)
Expert microscopy positive
n=2062 (46%)
Dead
n=142 (7%)
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Alive
n=1920 (93%)
Expert microscopy negative
n=2412 (54%)
Dead
n=292 (12%)
Alive
n=2120 (88%)
Reyburn H et al. BMJ 2004
Diagnostic contrasts: Malaria and other diseases
• ? TB:
• ? HIV:
• ? Influenza:
• ? Pneumonia:
• ? Typhus:
• ? ………
• ? Malaria:
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Treat if disease is confirmed
Treat if disease is confirmed
Treat if disease is confirmed
Treat if disease is confirmed (signs)
Treat if disease is confirmed
Guess, treat, and hope ….
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
Microscopy
RDT
Symptombased
Microscopy
RDT
Referral Hospitals
District Hospitals
Health Centers
Private Clinics
Aid Posts/Volunteers
Private Pharmacies
Households
DB. WHO/GMP
?
Conventional microscopy for malaria detection
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Malaria Rapid Diagnostic Tests (RDTs)
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Accurate malaria diagnosis can
now be accessible to all.
Courtesy: Malaria Consortium
DB. WHO/GMP
Senegal RDT implementation
(% of RDT use by month in 2007 - 2008)
Senegal malaria incidence among fever cases
50
% of fever
40
Large-scale RDT
introduction
30
20
10
0
2006
DB. WHO/GMP
Dec-07
Dec-08
Courtesy Babacar Faye and Senegal MoH
Uganda, RDT implementation
Weekly Malaria Lab. Tests, 2008, Kabale District: Uganda Saving costs by treating only lab confirmed case!
1200
1000
VALUES
800
600
400
200
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
0
2008
WEEKS
DB. WHO/GMP
Tested
Positive
Positivity (%)
Courtesy Uganda MoH,
Uganda WHO office
Scale up of RDTs and ACTs in India
12
Millions of kits/doses
10
8
6
RDT use
ACT use
4
2
0
2003
2004
2005
2006
2007
Source: personal communication: NMCP India, 2008
DB. WHO/GMP
12 month health worker follow-up Zambia 2007-8
Zambia NMCC, Mal Consortium, WHO, FIND, URC
Reported malaria cases, Zambia Livingstone
District, 2004 - 2008
14000
Introduction of RDTs
12000
10000
ACT
8000
6000
4000
IRS
Bednet introduction
2000
20
04
20 Q 1
04
20 Q 2
04
20 Q 3
04
20 Q
05 4
20 Q 1
05
20 Q 2
05
20 Q 3
05
20 Q
06 4
20 Q 1
06
20 Q 2
06
20 Q 3
06
20 Q 4
07
20 Q 1
07
20 Q 2
07
20 Q 3
07
20 Q
08 4
20 Q 1
08
20 Q 2
08
20 Q 3
08
Q
4
0
DB. WHO/GMP
Challenges to ensuring access to accurate RDTbased 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 products
Rnd 2 (2009) 27 products
Rnd 3 (2010): 47 products
WHO, FIND, TDR, US CDC
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Lot Testing
Collection and testing site
Specimen characterization
Regional lot-testing site
HTD
CDC
DMR
UCAD
UL
CIDEIM
IPB
EHNRI
IPC
RITM
KEMRI
IMT
IHRDC
IPM
AMI
2006: 41 lots
2007: 81 lots
2008: 167 lots
2009: 196 lots (?15% of
public sector procurement)
DB. WHO/GMP
2010: +++
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
Water added
Dried
antigen
Contents
placed on
RDT
Future lot-testing panels
1
2
Antigen types
3 4 5 6 7
8
9 10
Antigen
concentration
DB. WHO/GMP
Taking heath-worker training seriously - Zambia
Suite of products:
Job-aid
Training manual
Photographic result guide
Proficiency tests
100%
96%
90%
90%
86%
81%
80%
72%
70%
61%
60%
50%
40%
30%
20%
10%
0%
Test prep
Package directions
DB. WHO/GMP
RDT reading
Job aid only
Zambia MoH, URC, WHO, TDR, FIND, Malaria Consortium
Job aid + training
www.wpro.who.int/sites/rdt,
Managing fever, not malaria
Febrile patient
Anti-malarial medicine
Can of
worms…
RDT / microscopy
~20%
Malaria
Anti-malarial medicine
~80%
Non-malaria
Severe symptoms
Refer
DB. WHO/GMP
Not severe
Manage in community
? review
? Antibiotics
? Other
Minimum standard for funding a diagnostic programme?
Transport and storage
Training, drugs / supplies for non-malarial fever
Community education
Training and supervision
Monitoring accuracy in field
Lot-testing and laboratory monitoring
Procurement of gloves, sharps disposal containers etc
Procurement of RDTs
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
14000
Introduction of RDTs
Successful intervention
10 cases per month.
12000
10000
8000
6000
4000
IRS
Bednet introduction
Malaria now down from 1st to 16th district
health priority….other disease priorities
are more urgent
2000
20
04
20 Q 1
04
20 Q 2
04
20 Q 3
04
20 Q
05 4
20 Q 1
05
20 Q 2
05
20 Q 3
05
20 Q
06 4
20 Q 1
06
20 Q 2
06
20 Q 3
06
20 Q 4
07
20 Q 1
07
20 Q 2
07
20 Q 3
07
20 Q
08 4
20 Q 1
08
20 Q 2
08
20 Q 3
08
Q
4
0
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
Serology
Screen large
populations for signs
of recent malaria
transmission
Malaria LAMP
Detects 1 parasite/µL
Potential for district /
clinic level use
Find and treat malaria
‘carriers’
DB. WHO/GMP
Current maps of malaria incidence
WHO 2009
www.map.ox.ac.uk
2009
DB. WHO/GMP
Possible future for malaria??
Polio case numbers
1988: 350,000
1999: 7,141
2000: 2,979
2001: 483
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
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?
Thank you
DB. WHO/GMP