Malaria diagnosis: Moving from a mess to an ordered programme to a tool for elimination The AllParty

1
Malaria diagnosis Moving from a mess to an
ordered programme to a tool for
eliminationThe All-Party Parliamentary Group
on Malaria and Neglected Tropical Diseases
(APPMG)

• David Bell
• FIND
• Nov 2009

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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.

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Confirmation of diagnosis

• confirmation of parasitaemia in suspected
  malaria cases

World Malaria Report 2008
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Magnitude of over-diagnosis /over-treatment
Systematic review 24 studies conducted
between 1989 and 2005 in 15 different African
countries including 15331 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. DAcremont, C. Lengeler, B.
Genton, Philadelphia, November 2007
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Changing case managementManagement of febrile
illness
Febrile patient
Anti-malarial medicine
RDT / microscopy
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80
Malaria
Non-malaria
Severe symptoms
Not severe
Anti-malarial medicine
Manage in community ? review ? Antibiotics ? Other
Refer
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Can we ignore non-malarial fever?
High mortality among patients admitted to
hospital and incorrectly treated for malaria, 10
hospitals, NE Tanzania
Reyburn H et al. BMJ 2006
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RDT impact, Zambia
ACT
Source NMCC, Zambia MoH
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Senegal RDT implementation ( of RDT use by month
in 2007 - 2008)
Courtesy Babacar Faye and Senegal MoH
9
Senegal Parasite prevalence of malaria-like fever
cases
RDT introduction
Courtesy Babacar Faye and Senegal MoH
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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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Scale up of RDTs and ACTs in India
Millions of kits/doses
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Challenges to implementing comprehensive
RDT-based diagnosis

• Sensitivity e.g. 20 to 99 in published studies
• Stability
• Recommended storage temperature often
  inappropriate for rural health clinic in tropics
  (e.g. lt35C)
• User safety
• Blood safety (gloves, sharps disposal, HIV risk)
• Programmatic
• Managing negative results (non-malaria fever
  patients)
• Logistics
• Monitoring

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Building a structured diagnostics programme
Should be integrated where possible with
laboratory services for other diseases
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Selecting RDTs for procurement.WHO Product
Testing Round 1 2008-9
ALL 60 Manufacturers 200 products
ISO134852003 35 Manufacturers 112 products
Evaluated 2008 21 Manufacturers 41 products
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Selecting RDTs for procurement WHO Product
Testing 2008-9 Performance against 200 para/µL
samples
www.wpro.who.int/sites/rdt
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WHO-FIND Laboratory network
Lot Testing
Collection and testing site
Specimen characterization
Global specimen bank
Regional lot-testing site
HTD
CDC
DMR
UCAD
UL
IPB
RITM
IPC
EHNRI
CIDEIM
KEMRI
IHRDC
IMT
IPM
AMI

• Why lot-test?
• Lot-lot variation noted in most products
• Ensure no damage during transport to country
• Need to convince clinicians / users / regulatory
  authorities that tests are working

2006 41 lots 2007 81 lots 2008 167 lots
(?15 of public sector procurement)
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Innovative planning, infrastructure and training
SMS-based disease and stock reporting
Productive collaborations
Programme management
Standardized job-aids and training
Logistics manuals
18
Courtesy Malaria Consortium
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Minimum standard for funding a programme?
Transport and storage
Training, drugs / supplies for non-malarial fever
Community education

• To have an impact, we need to
• Build programmes, not just fund procurement
• Develop sustainable methods and in-country
  capacity

Training and supervision
Monitoring accuracy in field
Lot-testing and laboratory monitoring
Procurement of gloves, sharps disposal containers
etc
Procurement of RDTs
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In the pipeline 2010-2011Country based
lot-testing, clinic-based QC testing

• Recombinant antigen-based testing panels for
  RDTs
• Moving control of quality control to national
  programmes, and health workers, in endemic
  countries
• Harmonizing standards and RDT detection
  thresholds between developers, manufacturers and
  users

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Towards elimination Detection of P. falciparum
reservoir
Parasite density
HRP2 concentration
Average field microscopy
Good RDT
Expert microscopy
PCR
fever
months
Sampling visibility
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LAMP Moving molecular diagnosis from London to
Livingstone
Population screening and LAMP
In areas with low-transmission, a large
proportion of patients with malaria are likely to
have less than the 100 p/ml detected by RDTs.
Development underway of Loop-mediated isothermal
DNA amplification (LAMP) that detects 1-6
parasites /?l with minimal sample processing that
requires no sophisticated equipment and can be
read with the naked eye (FIND, HTD London, Eiken).
Primers amplifying Plasmodium mitochondrial DNA
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Potential for high through-put LAMP-based
screening
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Accurate diagnosis at community level Effort
and outcomes
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Acknowledgements

• WHO
• FIND
• HTD, UK
• RITM, Philippines
• IP, Cambodia
• US CDC
• AMI, Australia
• MSF
• DMR, Myanmar
• IP, Madagascar
• IP, Central African Republic
• IHDRC, Tanzania
• KEMRI, Kenya
• EHNRI, Ethiopia
• Uni Lagos, Nigeria
• UCAD, Senegal
• CIDEIM, Colombia
• IMT, Peru
• Zambia NMCC

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Addressing microscopy performance
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Introduction of a slide validation programme
(MSF, Sudan)
Addressing microscopy performance
Courtesy MSF, Holland
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Addressing microscopy performance
Asian accreditation network (WHO-ACTMalaria-AMI)
Africa Similar programmes at KEMRI, under
development through IMaD, Uni Lagos, elsewhere