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2.1 Dr. Miswar - Next Generation Diagnostic Multiplex & Syndrome Based Diagnostics Testing (MF, 13072019) - 1
2.1 Dr. Miswar - Next Generation Diagnostic Multiplex & Syndrome Based Diagnostics Testing (MF, 13072019) - 1
Current positio n
MaCPALM 2019
Makassar, July 13, 2019
Miswar Fattah
Specialty & Research Laboratory
Prodia Clinical Laboratory
miswar.fattah@prodia.co.id
miswarfattah@gmail.com
10 FUTURE LAB MED
• More Specialize & Unique Test
• More Simple Technology & Fast Results
• Shift from single to the multiplex & Syndrome based Test
• Increase of xPOCT
• Less Sample / mini sample
• High Personalize Test
• High IT utilization (Big Data, IoT & AI)
• Remove gap home care, Health care, research facility
• More Preventive test
• Increase DCT, test GO HOME
• •
•
•
TWEETPEE FROM PIXIE SCIENTIFIC
(A SMART DIAPER)
LESS SAMPLE & EASY PHLEBOTOMY
URINE TEST GO HOME
• 0
ANALOGY OF MULTI-LAYER GOOGLE MAPS AND PATIENT
INFORMATION GOES TO PRECISION MEDICINE
https://newsroom.fmcna.com/whitepapers/personalized-nephrology
100000 Healthy
50000
5000
NoSIRS
PS
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°'" c11..-Y1U1..
Bactenll In blood No
Temperature 38'1:
NoSIRS
PS
en suite tory
Healthy - - - Oesllnatlon path with optimal policy
•
SlmHar palieflt trajeaories
Current patient atate
- I
-
-50 SIRS
Respiratory Rate 20 SIRS -
-10000 Bact8f8ml8
WBC 12.9
Bacteremia . I
I
I . I
-12500 BPS BPS
-- --
4
SBP 91.8 I
-15000 PSS PSS
,,,... I
--
............... ....--....... SEPSIS
20 - ......... 72.3
�-
-40000 SEPSIS
I I I
-<0000
·100000 Oea1h
D--��
State diagram
-
ol...!:a:::::;::::::::;::::::::a;;==:::'..�'....:::;::!....::;;:::::'.....,,..c._L.:s���·'.'_ Ls�1:•�_J Sepllc-
Deatho
Belief
1 2 3 4 5 6 7
Day
6
Drug History
9 10 11 12 13 14
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Cetlriaxone
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Metronidazole, Ceftriaxone 500mg,2g
Septic Alternative Action
Shoe
ancom cm OOOm
Geographic Information System
of a Human Being
(Topol E, 2014)
TREND OF MULTIPLEX DRIVE BY TECHNOLOGY
xMAP
Qplex array
Biocode
Growing home-testing market to encourage further adoption of POC dev ces Competltion with centralized tabs and hospital stat
labs, reducing the rate of POCT adoption
CUA-waived status for lncreas ng the number of Infectious disease tests, enabling their usage by
healthcare providers in non·tradltlonat laboratory settings, Including physicians' offices
The lndustr(s continued push for a treatment paradigm shift to value·based and patient·
centered care
MULTIPLEX TESTING FOR RESEARCH
Sensitive Simple
Specific Rapid
Physician ch•cks
•
: In th• a bsenc• of
• Broad therapy RPSults a rrM
'
patH!nt for : t�t resuns physki.;in • ceounues wh,1• from lab. spec,flc
symptoms : his to administer waitinii for results th•rapy
: broad therapy from the lab commenc�s
Br�d-spectrum Br�d-spectrum Broad-spectrum
Specific lhe_r.ipy
Therapy Therapy Therapy
� � �
J.JI j.JI j.JI
� Gram /· F,nal 10 ess�
Cl
2-3 days
� I
I
I
lab techmcian
rece•= patient
l P•thoeens are 1nrttt1nii pathocen
sample, screened for Is Identified and ,ts
pathoeensare put morpholoilcal suscept1bthtY to
on overnight characterl<tks (ee antibt0t1cs is
Incubation Gram stalnlna) determined
INTRODUCTION
• Growing number of emerging pathogen makes it difficult for physicians to memorize the
actual list pathogen
• Change approach from testing most common agent first followed for rare agent to broad
syndrome-or disease base
• To date diagnostic kit have been developed for syndrome – or disease base kit : endocarditis,
pericarditis, diarrhoea, osteitis, meningitis, encepehalitis, uveitis, keratitis, sepsis, respiratory,
etc
• Rapid identification
(reduce mortality, Cost and
duration of hospitalization)
Bacteria
Parasite
Virus
ACUTE DIARRHEA
What is he actual prevalence
Virus
Bacteria
Parasite
Positive result = stop testing = save healthcare spending?
A. xTAG GPP
nI • •l+* •
B. Verigene EP
-�
-• - -
. .
.
--.::v
C. FilmArray GI
SEPSIS TEST
Blood from hospital
patient with Bacterial Viral
suspected infection 30-Day Mortality
Infection Infection
Not likely
viral
0.5
:,,
..
:r.
'
.
Example test report
··•••·-· ·-·
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'•.IL:�L..L::..:..:::....:.:.:.._.:....!...:..:..::L:...�
• 11 In ICW lmlcticW'I ( ) badll'III « W'II?
• Oilll)ltllntl'ECl,'ICU, kllk.dlb,11 �II
--
RESULTS – ANTIMICROBIAL STEWARDS
MALDI TOF
Complexity
LCMSMS
PCR, ELISA - Flowcytometry
Kim, H., Chung, D.-R. & Kang, M. Analyst 144, 2460–2466 (2019).
EXAMPLE XPOCT
Two-color LFAs for the m.ultlplex lgG/lgM detect(on or Dengue virus (lgG/lg_M)
s.eve_rat febrile lllnesses Chfkungunya virus (tgG/lgM)
Antibodies against HIV-1 arid -2.
Multiplex detection of humeral Immune r-esponses. to
Myoboa�rium cub�rcu/osls, and HepaUtls C
lnfec.t.lous disease paLhogens
Virus In plasma
TJ·u·ee-colored mult.lplexed lateral flow POC sensor for Dengue virus NS1 protein. Ye.now F-f!!!Vet Virus
the simultaneous dLagnos.ls of severe acute f�brlle NS1 protein, and Ebola virus, Zaire strain
Multlpte.xlng on
fllnesses gtycoi><otein GP
a sl n,gle strl p
Fast dlagnos,s of Scrub typhus in many endemk.
lgG and 1gM antibodies to 0. t:sutsugarnushl
regions
Stable multiplex LFA using AMP for the simultaneous
detection and identification of Ship toxln-produclng STEC 01.57, 026, and 0111
Esch�lchJo coll {STEC) serog_roup
Multl-plex diagnosis of HIV and HCV to Identify tlle co• Antl.. HIV tgG, Antl-HCV tgG, Anti-HAV lgG and
Infected Individuals lgM
Both detect.Ion and dlfferentLatlon of Influenza A and
Influenza A and 8 vin..,ses antigen
B type viruses In respiratory samples
Multiplex lmmuno-dlsc sensor fa< bacterial lnfe.ct:fon P�udornonos oerug;noso, Stophyloc.occ.u.s
Multlple.Jtlng with caused cystic fibrosis oureus
a mult.lple strip E. coll 015 7:H7. S. porotyphl A. S. porotyphl a.
Rapid, sl.multaneo-us detection of 10 epidemic
S. porotyphl C. S. typhl,, S. �nt�rltldis. S.
foodbome pathogens for food safety and Iow•
cho/eroe:sul-s� V. cho/tro 01, V. cholera 0139,.
occurrence of foodbome disease
and v, porohoemolytlcus
Integration of lateral fi<>'IN and Mala'1a antigen Plosrnodlurn folciporum
Mosqullo-control me.asunl!s In many endemic areas
h1s.tldlne-rlc.h protein 2
MULTIPLEXING LATERAL FLOW IMMUNOASSAY FOR
SIMULTANEOUS DETECTION OF AG/AB
(B)
i
Ta�et
lgG
;:�:i'."::t.
�t�· w �
Ta,gel
lgM
I Test region
1:
' Ill .i.l.i
(C) (D)
MULTIPLEX TESTING PANEL FOR DISEASE /
CLINICAL CONDITION
Sepsis panel
Multiplex
Multiplex PCR – Technology
ESI Mass pathogen
spectrometry panel* Multiplex PCR
- Microarray
S. il!;lill.!Ctiile E. f.1ec.1lis
S.pyogene.s E g;;illln;;irurn
- Adenovirus (AdV) - Chlamydia tree homatls (CD (CEO O 8 6) S. pneumoniae E f;;iecium
- Influenza A virus (FluA) - Neissena gononhoeae (NG)
- Influenza B virus (FluB) V 3 . St.ileJI¥ W O -C'l:I ll1J 9IJP..
- Trlchomonas var;;lnalls (TV)
- Parainfluenza virus1 (PIV1 ) - Mycoplasma norrnrno (M H) S ep,derrnld,.s
S. haernolyticu.s
- Parainfluenza virus2 (PIV2) - Mycoplasma r;;enltallum (MG) S. .1ureus
- Parainfluenza virus3 (PIV3) - U reaplasma urealytic um (U U)
- Parainfluenza virus4 (PIV 4) - U reeoteame oervurn (UP) V 4.Grarn (-) bactel"ia-A V 5. Gram(-) l>aclet'ia-A
- Rhinovirus A/B/C (HRV) - Internal control P. .1eruginos.1 S. rno1rcescens
- Internal control (IC) A. baumann1i B. fr;;igilis
S maltophll1a s typhi
06.Grarn(-)�B V 7. Gram(-) 1-aeria- B
PanelB
JC pneumon1ae E coll
«. oxytoca E csoeo ee
- Respiratory syncytial virus A (RSV A) P. miro1bilis E. .1erogenes
- Respiratory syncytial virus B (RSV B)
- Bocavirus 1 f2t314 (HBoV) V8.Fl.9,gi V 9 • Fungi
- Coronavirus 229E (CoV 229E) C. albican.s C. glabrata
- Coronavirus NL63 (CoV NL63) C. tropic.1Jis C. Xrus-ei
C par;;ip.s,Jo.s,s A fum,g;;itu.s
- Coronavirus OC43 (CoV OC43)
- Metapneumovirus (MPV)
- Enterovirus (HEV)
- Internal control (IC)
XTAG PATHOGEN PANELS
• Respiratory panel : AdV; influenza virus A (H1, H3); influenza virus B; MPV; PIV1, -2, -3;
RSV (A/B); RhV/EV
• Gastrointestinal Panel :
Benefit : time required for results fast 5-6 hours, degree of multiplex >15
Throughput moderate/high, available for quantitative,
Limitation : not full integrated, cannot for near patient facility, moderate carryover contamination risk, high complexity
INFINITI PANELS
Benefit : time required for results fast 6 -10 hours, degree of multiplex >15
Throughput moderate/high,
Limitation : not full integrated, cannot for near patient facility, moderate carryover contamination risk, high
complexity, cannot quantification
FILM ARRAY PANEL
Respiratory panel BLOOD CULTURE IDENTIFICATION (BCID) PANEL GASTROINTESTINAL PANEL
I . Ii tlH,
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:\i I.Iii i:-ol O
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gr°''" o �.J 110 1 I I I I
911 I I I I I I
1111111 I
0•1-• Ao"r•<
"'mi,hfied D'- .-.. PCR-ESI )TOF M<; hydroly'$is
Urine '5a-"Tnfl4r" J
POCT MULTIPLEX TESTING
F@Ver In returnilng
trilve.Uer.1
Pla-.modium 'PP•
Dengue y,ru!t
f'neumunl.a JnflV<l!"nLa C.s.troent.eritls
vrecoes A:e�1ra1ocy Rorwonrus
s)'ncyt.lal vlrus Adenc>Vlr�1oi�
Mycop(asmo pn1::umonloe crosrr1d1um dlffrtilc
8ordeteUa pertll.li1'i Ht'!llc:obucr1""r pyf'11f"i
�tophy1ucoccus au, l!us
Ptt.NI mocystJ<. Jlf"Ovl"¥:"U S1nl ONA 1!1\.1'ctctor
Lt"gloffltlra 11rlno,f") 4!ntlgl:'n
Pn�vmococcol urinary
.U.Ligt,n
Con"'-'1,u,·
•
Heq><:!'� ,iMpkx .... i,u-,. pneurnon;oe
Slr't'PIOCVCl"US
�.
HIV Pneumococcol urinary
Chfom)d'io 1rachomatu, anfj:g,("n
Cryp1ococcu.s neaformaru
CONCLUSIONS
• Increase number emerging technology possible for multiplex testing in Clinical
Microbiology
• Clinical microbiology testing move to test syndrome- and disease base panels
• More studies need to fully elucidate characteristic performance for each technology