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Tuberculosis Ruth McNerney Department of Pathogen Molecular Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine. STATE OF THE ART MALARIA, TYPHOID, DENGUE DIAGNOSTICS Rosanna W Peeling Olivia Varsaneux London School of Hygiene and Tropical Medicine United Kingdom
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STATE OF THE ART Tuberculosis MALARIA, TYPHOID, · PDF file•TUBEX® and Typhidot

Feb 21, 2018

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Page 1: STATE OF THE ART Tuberculosis MALARIA, TYPHOID,  · PDF file•TUBEX® and Typhidot

Tuberculosis

Ruth McNerney

Department of Pathogen Molecular Biology,

Faculty of Infectious and Tropical Diseases,

London School of Hygiene & Tropical Medicine.

STATE OF THE ART

MALARIA, TYPHOID, DENGUE

DIAGNOSTICS

Rosanna W Peeling

Olivia Varsaneux

London School of Hygiene and Tropical Medicine

United Kingdom

Page 2: STATE OF THE ART Tuberculosis MALARIA, TYPHOID,  · PDF file•TUBEX® and Typhidot

State of the Art Diagnostics for Malaria

Page 3: STATE OF THE ART Tuberculosis MALARIA, TYPHOID,  · PDF file•TUBEX® and Typhidot

Improving health worldwide

Product name Column1 Manufacturer

CareStart™

Malaria HRP2 (Pf)

Access Bio, Inc

Malaria HRP2/pLDH (Pf)

Malaria pLDH (PAN)

Malaria HRP2/pLDH (Pf/Pv) COMBO

Malaria HRP2/pLDH (Pf/PAN) COMBO

First Response™ Malaria Ag P. falciparum (HRP2) Card Test

Premier Medical Corporation

2015 WHO List of Pre-

Qualified Malaria RDTs

WHO/TDR/FIND Evaluation of Malaria RDTs

Total recommended:

• 25 Pf only tests

• 18 Pf/pan tests

Page 4: STATE OF THE ART Tuberculosis MALARIA, TYPHOID,  · PDF file•TUBEX® and Typhidot

Slide title here

Positive Control Wells

Assuring the Quality of Malaria RDTs

Field Tested at the Lao Oxford Mahosot Wellcome Trust Research Unit (LOMWRU)

and by the Malaria Consortium

Page 5: STATE OF THE ART Tuberculosis MALARIA, TYPHOID,  · PDF file•TUBEX® and Typhidot

CareStart™ G6PD RDT

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the

most widespread enzyme defect that can result in red cell breakdown when

exposed to some medicines, including antimalarials

Dennis Adu-Gyasi et al. PloS one. 2015:

Reference Assay Sensitivity Specificity

Trinity Qualitative 100% 72.1%

Trinity Quantitative 98.9% 96.2%

Detecting G6PD Deficiency

Page 6: STATE OF THE ART Tuberculosis MALARIA, TYPHOID,  · PDF file•TUBEX® and Typhidot

State of the Art Diagnostics

and Unmet need for Typhoid

Page 7: STATE OF THE ART Tuberculosis MALARIA, TYPHOID,  · PDF file•TUBEX® and Typhidot

Assay Sensitivity (95% CI) Specificity (95% CI)

Cromotest O: single tube Widal 87%(76.5-94.4) 7%(0.8-22.8)

Cromotest H: single tube Widal 95%(86.5) 14%(3.9-3.17)

TUBEX 73%(60.3-83.4) 69%% ( 49.2–84.7)

Typhoid IgM 75%(61.1-86.0) 61%(40.6-78.5)

Typhoid IgG 69%(54.9-81.3) 70%(49.8-86.2)

Performance of Typhoid Tests • semiquantitative slide agglutination and single-tube Widal tests performed

poorly.

• TUBEX® and Typhidot® may be suitable when pretest probability is high

and blood cultures are unavailable

• Performance of RDTs does not justify deployment in routine care settings in

Africa

Keddy et al. WHO Bull. 2011

Parry et al. 2015

Ref: blood culture and/or PCR+

N = 304, Bangladesh

Page 8: STATE OF THE ART Tuberculosis MALARIA, TYPHOID,  · PDF file•TUBEX® and Typhidot

State of the Art Diagnostics

and Unmet Needs for Dengue

Page 9: STATE OF THE ART Tuberculosis MALARIA, TYPHOID,  · PDF file•TUBEX® and Typhidot

NS1

0 4 6 14

IgM

IgG

days

An

tib

od

ies q

uan

tifi

ed

by E

LIS

A

viremia

RT

-PC

R

21 50

Acute illness

NS1

0 4 6 14

IgM

IgG

days

An

tib

od

ies q

uan

tifi

ed

by E

LIS

A

viremia

RT

-PC

R

21 50

Acute illness

Timing affects the Sensitivity of Dengue Case Detection

Days after onset of fever

Page 10: STATE OF THE ART Tuberculosis MALARIA, TYPHOID,  · PDF file•TUBEX® and Typhidot

Patient Management:

confirm clinical diagnosis

• Confirmed diagnosis:

– Virus isolation

– Nucleic acid detection

– (Antigen detection)

– Seroconversion for IgM

– 4-fold rise in IgG titres

• Highly suggestive:

– IgM positive

Surveillance/measure

impact of interventions:

- IgM positivity

- virus isolation/nucleic acid detection

Outbreak investigations:

- IgM positivity

- virus isolation/nucleic acid

detection and to identify genotype

Vaccine/drug trials:

- Best/most feasible diagnostic

methods to define a dengue

infected patient (and to identify the genotype)

Use of Diagnostic Tests for Dengue

Page 11: STATE OF THE ART Tuberculosis MALARIA, TYPHOID,  · PDF file•TUBEX® and Typhidot

Liz Hunsperger Sutee Yoksan

S. Vazquez

“Pedro

Kouri”

Institute of

Tropical

Medicine,

Cuba

D. Enria

Instituto

Nacional de

Enfermedade

s Virales

Humanas,

Argentina

P. Vasconcelos

Instituto

Evandro

Chagas, Belem,

Brazil

S. Devi

University

of Malaya,

Malaysia

V. C. Nguyen

Hospital for

Trop. Diseases,

Ho Chi

Minh City ,

Vietnam

P. Buchy

Pasteur

Institute,

Phnom

Penh,

Cambodia

Reference Centre for Americas

CDC Dengue Laboratory

San Juan, Puerto Rico

Evaluation

Laboratory 4

Evaluation

Laboratory 3

Evaluation

Laboratory 2

Evaluation

Laboratory 1 Evaluation

Laboratory 5

Evaluation

Laboratory 6

Reference Centre for Asia

Mahidol University

Bangkok Thailand

PDVI-WHO/TDR Laboratory Network

Page 12: STATE OF THE ART Tuberculosis MALARIA, TYPHOID,  · PDF file•TUBEX® and Typhidot

Performance of Dengue IgM ELISAs

40

50

60

70

80

90

100

Th

aila

nd

Ca

mb

od

ia

Ma

laysia

Vie

tna

m

Pu

ert

o

Ric

o

Arg

en

tin

a

Cu

ba

Sen

sit

ivit

y (

%)

Focus (98.0)

Omega M (60.3)

Omega M Capture

(60.6)

PanBio (98.8)

Standard (96.3)

Hunsperger et al Emerg Infect Dis.

15:436-40, 2009; www.who.int/tdr

40

50

60

70

80

90

100

Th

aila

nd

Ca

mb

od

ia

Ma

laysia

Vie

tna

m

Pu

ert

o

Ric

o

Arg

en

tin

a

Cu

ba

Sp

ecif

icit

y (

%)

Focus (81.7)

Omega M (84.6)

Omega M Capture

(97.8)

PanBio (86.6)

Standard (87.8)

Page 13: STATE OF THE ART Tuberculosis MALARIA, TYPHOID,  · PDF file•TUBEX® and Typhidot

Performance of Dengue IgM Rapid Tests

0

10

20

30

40

50

60

70

80

90

100

Thailand

Cam

bodia

Mala

ysia

Vie

tnam

Puert

o R

ico

Arg

entina

Cuba

Sen

sit

ivit

y (

%)

PanBio (76.5)

Pentax (97.1)

Standard (59.9)

Zephyr (20.1)

Hunsperger et al Emerg Infect

Dis. 15:436-40, 2009;

www.who.int/tdr

40

50

60

70

80

90

100

Thaila

nd

Cam

bodia

Mala

ysia

Vie

tnam

Puert

o

Ric

o

Arg

entina

Cuba

Sp

ecif

icit

y (

%)

PanBio (91.3)

Pentax (78.2)

Standard (90.4)

Zephyr (86.5)

Page 14: STATE OF THE ART Tuberculosis MALARIA, TYPHOID,  · PDF file•TUBEX® and Typhidot

Dengue IgM ELISAs: False Positive Results

Page 15: STATE OF THE ART Tuberculosis MALARIA, TYPHOID,  · PDF file•TUBEX® and Typhidot

Rapid Dengue IgM Tests: False Positive Results

Page 16: STATE OF THE ART Tuberculosis MALARIA, TYPHOID,  · PDF file•TUBEX® and Typhidot

NS1 Tests

Page 17: STATE OF THE ART Tuberculosis MALARIA, TYPHOID,  · PDF file•TUBEX® and Typhidot

Sensitivity of NS1 Tests Varies by #Days

Post Onset of Fever

NS1 TESTS Days 0-5 Day 6-14

Company Sensitivity* 95% CI Sensitivity** 95% CI

ELISA Bio-Rad 60% (46–75) 29% (19–39)

Panbio 75% (67–83) 19% (11–27)

SD 70% (62–79) 31% (21–40)

RDT

Bio-Rad

52%

(45–59)

19%

(13–25)

CTK 40% (31–49) 19% (13–35)

Panbio 60% (54–67) 12% (7–17)

SD duo IgM/NS1

59% (52–66) 59% (51–66)

*Comparison to RT-PCR DENV positive samples

**Comparison to IgM seroconversion Number of samples tested differed to total number due to either duplicates for RDTs

invalid or equivocal result

Hunsperger et al PLoS One 8:e3171 2014

Page 18: STATE OF THE ART Tuberculosis MALARIA, TYPHOID,  · PDF file•TUBEX® and Typhidot

Tests for Detecting Active Dengue Infection

• IgM Tests

– A few dengue IgM ELISAs evaluated showed performance of >95%

sensitivity and >80% specificity, and gave consistent results across sites

– The sensitivity of dengue IgM rapid tests need improvement, with

significant variability from site to site

• NS1:

– NS1 ELISAs showed sensitivities of 60-75% and specificities of 71-80%.

– NS1 RDTs showed sensitivities of 40-60% and specificity 76- 80%

– NS1 tests are not recommended for use in patients 5 days post onset of

fever

• Dual NS1-IgM rapid tests show promise in detecting active

infection

Page 19: STATE OF THE ART Tuberculosis MALARIA, TYPHOID,  · PDF file•TUBEX® and Typhidot

Thank you