Transcript Slide 1

Assessment of three new parasite lactate
dehydrogenase (pan-pLDH) tests for
diagnosis of uncomplicated malaria
Fogg CL1, Nabasumba C1, Twesigye R1, Batwala V2, Piola P1,
Kiguli J1, Mutebi F1, Hook C3, Guillerm M4, Moody A4,
Guthmann J-P1
1Epicentre, 2Mbarara
University of Science and Technology,
3MSF - Malaria Working Group, 4MSF – Access Campaign
Background
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Microscopy = recommended method for malaria
diagnosis:
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Trained staff
Quality equipment
Supervision
Rapid diagnostic tests (RDT) are useful for
malaria diagnosis where high standard
microscopy is not available:
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Easy to use
Simple to interpret
Study rationale
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Most common RDT detect Histidine Rich
Protein 2 (HRP2), i.e. Paracheck®
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HRP2 tests have 2 major drawbacks:
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New RDTs detect parasite Lactate
DeHydrogenase (pLDH):
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Only detect P. falciparum
Remain positive for weeks after treatment
Identify all plasmodium species
Become negative quickly after treatment
The study assessed 3 new pLDH tests
Objectives
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Primary objective
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Measure validity of 3 pLDH tests and that of
Paracheck ®
Secondary objectives
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Measure % of positive tests after effective
treatment
Ease of use
Measure inter-reader reliability
Methods I: Inclusion
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Screening at OPD of Mbarara hospital
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Inclusion:
 symptoms of simple malaria
 signed informed consent
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Two age groups: “under 5” and “5 and above”
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Sample size: 400 patients (200 blood smear [+] and 200
blood smear [-])
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All tests were double read, blinded and compared to
microscopy
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Reading of blood smears controlled in Thailand
Methods II: Tests performed
1
2
3
4
Methods III: Follow-Up
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Patients:
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Positive BS on D0
OR At least 1 positive RDT on D0
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Positive BS on D0 treated with Coartem®
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Pregnant women were excluded
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Procedures on D3 & D14:
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Clinical examination
Blood smear
All tested RDTs
Methods IV: Outcomes
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Validity:
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Sensitivity: % of true positives
Specificity: % of true negatives
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Percentage of RDTs remaining positive at D3 &
D14
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Inter-reader reliability: kappa coefficient (above
0.80 was considered « Good Agreement»)
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Ease of use determined by a score
Results (I): Validity
Sensitivity
(N=248)
94%
Specificity
(N=212)
87.3%
[90.2 - 96.6]
[82.0 – 91.4]
Vistapan®
91.9%
89.6%
[87.8 – 95]
[84.7 – 93.4]
Carestart®
95.6%
[92.2 – 97.8]
84.7 %
91.5%
[79.6 – 88.9]
[90.3 – 97.0]
Paracheck®
Parabank®
[86.9 – 94.9]
94.3%
Results (II): Sensitivity by group
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Parasite density:
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Sensitivity decreased with parasitemia
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Parasitaemia <100 parasites/µL (from 41.9%
[Parabank] to 67.7% [Carestart])
Age group:
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Sensitivity increased in under 5’s
From 95.3% [Parabank] to 97.7% [Vistapan/Carestart])
Results (III): Positive tests after
treatment
pLDH
HRP2
Day 3
Day 14
Parabank ®
17.8%
[12.5 – 23.1]
4.6%
[1.7 – 7.5]
Vistapan ®
36.1%
[29.7 – 42.5]
8.9%
[5.1 – 12.7]
Carestart ®
42.5%
[36.1 – 48.9]
9.5%
[5.6 – 13.4]
Paracheck ®
86.2%
[81.7 – 90.7]
69.7%
[63.1 – 75.7]
Results (IV): Reliability
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Kappa above 0.9 for inter-reader
reliability for all tests
Results (V): Ease of use
CHARACTERISTIC
Paracheck
Vistapan
Carestart
Parabank
I Performance
21
30
18
21
II Safety
7.5
7.5
15
7.5
III Result stability
5
5
5
5
IV Interpretation
30
21
21
30
V Storage
20
20
20
12
83.5
83.5
79
75.5
TOTAL (/100)
Conclusions
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Carestart and Vistapan best tests:
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Parabank (poorly sensitive)
Paracheck (high % of positives at D14)
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Carestart and Vistapan could replace
Paracheck for malaria diagnosis in subSaharan Africa
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However, pLDH tests have slightly higher
costs ($0.6 to $0.7 vs $0.45 for Paracheck)
Acknowledgements
Thanks to:
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Mbarara University of Science & Technology
Study team and patients in Mbarara.
Malaria Working Group, MSF.
Access to Essential Medicines Campaign, MSF.
The test manufacturers.
Shoklo Malaria Research Unit.
Validity details
PARACHECK
VISTAPAN
CARESTART
PARABANK
Sensitivity
(N=248)
94% (n=233)
[90.2 - 96.6]
Specificity
(N=212)
87.3% (n=185)
[82.0 – 91.4]
91.9% (n=228)
[87.8 – 95]
95.6% (n=237)
[92.2 – 97.8]
89.6%(n=190)
[84.7 – 93.4]
91.5% (n=184)
[86.9 – 94.9]
84.7 % (n=210)
[79.6 – 88.9]
94.3% (n=200)
[90.3 – 97.0]
Positive Tests D3/D14 details
Day 3
Day 14
Parabank
17.8%
[12.5 – 23.1]
(36/202)
4.6%
[1.7 – 7.5]
(9/196)
Vistapan
36.1%
[29.7 – 42.5]
(79/219)
8.9%
[5.1 – 12.7]
(19/213)
Carestart
42.5%
[36.1 – 48.9]
(97/228)
9.5%
[5.6 – 13.4]
(21/221)
Paracheck
86.2%
[81.7 – 90.7]
(193/224)
69.7%
[63.1 – 75.7]
(152/218)
pLDH
HRP2
PPV & NPV
PARACHECK
Sensitivity
Specificity
PPV
NPV
VISTAPAN
CARESTART
PARABANK
91.9%*
95.6%*
84.7 %
[90.2 - 96.6]
[87.8 – 95]
[92.2 – 97.8]
[79.6 – 88.9]
87.3%
89.6%
91.5%*
94.3%*
[82.0 – 91.4]
[84.7 – 93.4]
[86.9 – 94.9]
[90.3 – 97.0]
89.6%
91.2%*
92.9%*
94.6%*
[85.3 – 93]
[87 – 94.4]
[89.1 – 95.8]
[90.7 – 97.2]
92.5%*
90.5%*
94.6%*
84.0%
[87.9 – 95.7]
[85.7 – 94.1]
[90.6 – 97.3]
[78.7 – 88.4]
94%*
Methods V: External Quality
Control
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External quality control performed at
Shoklo Malaria Research Unit, Thailand
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Randomly selected 145 positive slides and
145 negative Day 0 slides.
Results (VI): Quality control of
slides
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Number of discordances: 7 out of 145 (<5%)