Editor – Sweis and colleagues showed discrepancies between histology and serology in the diagnosis of coeliac disease (CD) (Clin Med August 2009 pp 346–8),
Our understanding of the clinical features and impor- tance of coeliac disease (CD) has been completely transformed in the last decade, thanks to three key
serology is superior in comparison with other diagnostic methods because it is simple, inexpensive, between serology and histopathology is important for
The histology is characterized by a granulomatous response composed of histiocytes, giant cells, and lymphocytes associated with fibroblastic activity16,24,26,
histological identification of H pylori or- ganisms are superior to two established culture, serology, and histology) compare the methods Results
of the small portal bile ducts; in the early stages true Serological and histological diagnosis ofprimary biliary cirrhosis copyright
11 nov 2013 · authors aimed to make a comparison between serology and histology for detection of Helicobacter (H ) pylori infection Among the 50 study
authors aimed to make a comparison between serology and histology for detection of Helicobacter (H ) pylori infection Among the 50 study subjects, 30 ( 60 )
the difference in time involved makes for a significant serology in the diagnosis of coeliac disease (CD) (Clin sensitivity of histology is largely dependent
Different invasive and non-invasive diagnostic tests are available for the diagnosis histology and culture are important in the assessment of H pylori status
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Microbiological and serological diagnostic
test s fo r Helicobacter pylori: a n overvie w Your i Glupczynsk i
Service
de Biologie Clinique, Cliniques Universitaires UCL de Mont-Godinne, Yvoir, Belgium
Differen
t invasiv e an d non-invasiv e diagnosti c test s ar e availabl e fo r th e diagnosi s o f H. pylori i n th e individua l patient . I n practice , endoscopi c test s ar e bes t fo r a primar y diagnosi s o f H. pylori infectio n becaus e endoscop y allow s assessmen t o f treatmen t indications . Th e ne w rapi d ureas e test s ma y hel p th e clinicia n i n treatmen t decision-making . Cultur e i s currentl y no t recommende d fo r routin e evaluation , bu t i t i s becomin g increasingl y importan t i n certai n population s wit h highe r prevalenc e o f dru g resistance , sinc e i t allow s testin g fo r susceptibilit y t o antibiotics . Serologica l testin g ha s bee n recommende d fo r initial pre-endoscop y o r pre-treatmen t screenin g i n dyspepti c patients . However , severa l curren t 'in-office ' test s appea r insufficientl y accurat e o r woul d nee d further validatio n befor e bein g recommende d fo r us e i n clinica l managemen t strategie s a t a primar y car e level . Th e ure a breat h test s ar e bes t suite d t o confir m eradicatio n earl y afte r treatment , whil e laborator y serolog y test s ar e o f limite d use , sinc e 6 month s ar e require d befor e a resul t ca n b e obtained . Th e serologica l offic e test s canno t b e use d fo r post-treatmen t assessmen t o f H. pylori status .
Correspondence
to: Dr Y.
Glupczynski,
Service de
Biologie
Clinique,
Cliniques
Universitaires UCL de Mont-Godinne, 1 Av. Dr G . Therasse,
B-5530
Yvoir, BelgiumThe recognition that H. pylori plays a pivotal role in the pathogenesis of severa l gastroduodena l pathologie s make s it s diagnosi s necessar y i n man y differen t circumstances . Sinc e th e origina l descriptio n o f th e organis m b y
Marshal
l an d Warre n i n 1982
1 , numerou s reliabl e invasiv e an d non - invasiv e diagnosti c test s hav e bee n developed . Eac h ha s advantage s an d disadvantage s whic h wil l mak e i t mor e o r les s appropriat e dependin g o n th e clinica l situation . Th e invasiv e biopsy-base d test s whic h includ e rapid ureas e test , histolog y an d cultur e ar e importan t i n th e assessmen t o f H. pylori statu s pre-treatment , a s endoscop y allow s assessmen t o f treatmen t indication s suc h a s ulce r disease 2 . Th e non-invasiv e test s obviat e th e nee d fo r endoscop y an d compris e serolog y an d th e ure a breat h test , usin g eithe r 13 C o r 14 C . I n vie w o f th e patch y distributio n o f H. pylori, al l biopsy-base d test s ma y theoreticall y fai l t o diagnos e th e infection . Th e inheren t ris k o f samplin g erro r can , however , b e virtuall y eliminate d b y obtainin g severa l biops y sample s fro m th e gastri c corpu s a s wel l a s th e fro m th e antrum 3 . I n contras t t o
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Helicobacter infection
biopsy-base d methods , non-invasiv e test s asses s th e globa l presenc e o f H. pylori i n th e stomac h eve n whe n th e bacteri a ar e irregularl y dis - tribute d o n th e gastri c mucosa . No n endoscopi c tests , particularl y serology , ar e cheape r an d mor e convenient , an d thu s shoul d b e preferre d i n situation s wher e th e additiona l informatio n yielde d b y a n endoscop y i s not needed . Th e ai m o f thi s pape r i s t o revie w curren t microbiologica l diagnosti c modalitie s fo r H. pylori an d t o emphasis e thei r preferentia l indication s takin g int o accoun t th e particula r setting s i n whic h a diagnosi s i s t o b e mad e (pre-treatmen t screenin g o r follow-u p afte r treatment) . I t als o give s a brie f overvie w o f th e deficiencie s o f curren t test s an d o f expecte d futur e developments .
Invasiv
e test s
Urease
tests Th e ureas e test s provid e a simple , rapi d an d cost-effectiv e metho d fo r th e detectio n o f H. pylori. However , th e practica l valu e o f thes e test s depend s no t onl y o n thei r sensitivit y an d specificity , bu t als o o n thei r speed , henc e makin g the m a practica l too l fo r th e endoscopis t i n decision-makin g a s t o whethe r o r no t therap y shoul d b e prescribed . Amon g th e variou s rapi d ureas e test s whic h hav e bee n describe d i n th e literature , severa l wer e foun d t o lac k sensitivit y whe n earl y readin g wa s performe d (withi n 1 h) .
Differen
t method s hav e bee n propose d t o speed-u p colou r change , suc h a s pre-heatin g o f th e ki t o r incubatio n at37° C o r higher . Yousf i et al 4 foun d tha t th e diagnosti c yiel d fo r detectin g H. pylori b y th e rapid ureas e tes t wa s no t adversel y affecte d b y th e siz e o f th e biops y forceps , whil e Lain e et al 5 showe d tha t increasin g th e amoun t o f tissu e i n CLO-test s di d significantl y haste n th e developmen t o f positiv e tests . I n anothe r study , Wo o et al 6 investigate d th e bes t gastri c sit e fo r obtainin g a positiv e rapi d ureas e test . The y foun d tha t biopsie s fro m th e gastri c angulu s ha d th e highes t sensitivit y fo r th e detectio n o f H. pylori a s compare d t o th e prepylori c an d corpu s sites . Interestingly , th e media n tim e t o positivit y was simila r wit h th e angulu s an d prepylori c sites , but i t wa s significantl y shorte r tha n fo r th e biopsie s fro m th e corpu s (6 0 versu s 18 0 min , respectively) . Malfertheine r et aV evaluate d com - parativel y tw o commercia l rapi d ureas e tests , th e HUT-tes t an d th e
CLO-test
. Bot h test s displaye d comparabl e sensitivitie s an d specificitie s (93 % an d 100
% fo r th e HUT-test ; 88
% an d 100
% fo r th e CLO-test ) despit e th e fac t tha t tw o biops y sample s (antru m an d dista l gastri c body ) ha d bee n obtaine d fo r th e HUT-tes t whil e onl y on e antra l specime n wa s 17 6 British Medical Bulletin 1998;5
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Practical diagnosis of H. pylori
sample d i n th e CLO-test . The y conclude d tha t th e samplin g o f on e additiona l gastri c biops y di d no t improv e significantl y th e diagnosti c efficac y i n untreate d patients , but tha t i t coul d b e require d followin g treatmen t wit h proto n pum p inhibitors , sinc e i n thi s case , H. pylori i s mor e likel y t o b e foun d onl y i n th e bod y mucos a an d not i n th e antrum . I n recen t years , newe r generation s o f commercia l test s hav e bee n introduce d o n th e market . On e o f suc h stri p test , th e Pyloritek ® i s designe d t o giv e a 1 h reading , withou t requirin g specia l incubatio n temperature s whil e allowin g severa l biopsie s t o b e teste d a t th e sam e time .
Severa
l studie s hav e show n tha t th e Pyloritek ® provide s a sensitivit y (90-99% ) an d a specificit y (95-100% ) a t leas t equivalen t t o thos e achieve d b y th e CLO-tes t o r othe r agar-base d test s afte r 12-2 4 h 8 " 10 .
However
, th e averag e tim e require d t o achiev e a positiv e resul t wa s onl y 20-3 0 mi n wit h th e Pyloritek ® versu s 120-15
0 mi n wit h th e agar-base d tests , an d th e forme r tes t wa s foun d t o b e significantl y mor e sensitiv e a t 1 h tha n al l othe r ureas e test s withou t compromisin g specificity .
Culture
Cultur
e undoubtedl y constitute s th e mos t specifi c wa y t o establis h th e diagnosi s o f H. pylori infection , bu t it s sensitivit y ha s bee n foun d t o var y greatl y betwee n centres . Th e difference s i n performance s observe d betwee n laboratorie s probabl y reflec t difference s i n expertis e wit h cultur e techniques .
Althoug
h i t i s stil l generall y considere d a s a tediou s procedure , cultur e ca n nowaday s b e performe d wit h minima l difficultie s i n almos t ever y genera l hospita l wit h a standar d microbiolog y laboratory . Cultur e is , however , no t necessar y fo r th e routin e diagnosi s o f H. pylori infectio n becaus e othe r invasiv e test s wil l detec t th e organism s i n mos t patients . On e o f th e majo r advantage s o f cultur e i s tha t i t allow s sensitivit y testin g o f H. pylori t o th e agent s use d i n th e treatment . Thi s i s particularl y importan t fo r th e clinicia n wh o mus t manag e patient s i n who m antibiotic - resistan t isolate s ar e suspecte d (e.g. i n area s wit h hig h rate s o f resistanc e t o antimicrobia l drugs ) o r thos e wh o hav e faile d wit h antimicrobia l dru g regimen s know n t o selec t fo r th e developmen t o f resistance 3 .
Althoug
h th e ris k o f samplin g erro r i s probabl y lowe r tha n generall y supposed , i t i s advisabl e t o tak e tw o biops y sample s fo r culture . Cultur e fro m eithe r th e antru m o r th e corpu s ha s a n excellen t diagnosti c yiel d i n untreate d patients , bu t samplin g o f bot h gastri c site s i s recommende d followin g treatmen t i n orde r t o optimiz e th e detectio n o f H. pylori 11 ' 12 .
Anothe
r facto r tha t ma y influenc e th e succes s rat e o f cultur e involve s th e transpor t condition s fro m th e endoscop y roo m t o th e laboratory .
Severa
l liqui d o r semi-soli d transpor t medi a hav e bee n recommended , bu t
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Helicobacter infection
i t i s no t clea r whethe r a specifi c mediu m compositio n i s superio r fo r thi s purpose . Roosendaa l et at 13 di d no t fin d qualitativ e difference s betwee n fiv e differen t media , althoug h quantitativ e dat a wer e no t shown . I n severa l o f th e abov e mentione d studies 11 - 13 , th e recover y rate s o f H. pylori fro m gastri c biopsie s wer e no t adversel y affecte d b y a dela y o f cultur e u p t o 2 4 h whe n transpor t medi a wer e hel d a t roo m temperature . Fo r trans - portatio n o r storag e longe r tha n 2 4 h a lowe r temperatur e might , however , b e a n importan t facto r fo r survival . Ha n et at 14 foun d a 100
% cultur e recover y fro m 1 6 gastri c biopsie s o f H. pylori-positive patient s store d i n a cystein e + 2 % glycero l transpor t mediu m store d a t -20° C fo r 4 week s versu s onl y 57
% afte r 1 2 week s storage . Recover y figure s whe n storag e wa s a t +4° C wer e 81
% an d 19% .
Differen
t cultur e medi a hav e bee n propose d fo r growt h o f H. pylori. I n on e recen t study , i n whic h severa l conventiona l medi a wer e compared , brai n hear t infusio n (BHI ) aga r supplemente d wit h 7 % lyse d hors e bloo d yielde d th e highes t isolatio n rat e an d th e highes t numbe r o f H. pylori colonies 15 . I t i s probable , however , tha t th e us e o f freshl y prepare d medi a rathe r tha n th e mediu m itsel f accounte d fo r th e succes s o f BH I aga r i n thi s study . T o suppres s th e growt h o f endogenou s o r exogenou s contaminatin g bacteria , selectiv e medi a ar e require d t o improv e th e isolatio n o f H. pylori fro m biops y samples 3 ' 1112
. Severa l selectiv e cultur e medi a hav e bee n develope d fo r optima l isolatio n o f H. pylori. I n a larg e comparativ e study , BH I aga r supplemente d wit h 10 % shee p blood , polymyxi n B , vanco - mycin , trimethopri m an d amphoterici n B yielde d th e highes t isolatio n rat e (99%) an d wa s foun d t o b e superio r t o Skirrow' s selectiv e mediu m (71 % isolatio n rate ) fo r primar y isolatio n o f H. pylori fro m gastri c biops y specimens 16 . However , combinatio n o f a t leas t on e selectiv e an d on e non - selectiv e cultur e mediu m i s generall y advocated , sinc e n o singl e cultur e mediu m allow s a 100
% recover y rat e o f H. pylori an d becaus e cultur e contaminatio n occur s i n abou t 25
% o f th e cases 11 - 12 . Th e patient' s oropharyngea l flor a ca n als o markedl y reduc e th e isolatio n rate s an d th e colon y number s o f H. pylori. I n on e study 17 , rinsin g o f th e biopsie s i n steril e salin e wa s show n t o improv e th e recover y o f H. pylori i n nearl y 40
% o f th e culture s processed .
Finally
, failur e t o detec t H. pylori b y cultur e ma y b e du e t o insufficien t duratio n o f incubation . Incubatio n period s o f u p t o 1 0 day s ar e usuall y recommende d i n orde r t o optimis e th e cultur e isolatio n rates , especiall y i n a post-treatmen t setting 11 ' 12 .
Polymerase
chain reaction (PCR) PC R i s regarde d a s th e mos t sensitiv e techniqu e fo r th e detectio n o f micro-organisms . Th e detectio n o f H. pylori i n gastri c biops y sample s o r 17 8 British Medical Bulletin 1998;5
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Practical diagnosis of H. pylori
i n gastri c juic e aspirate s b y PC R ha s bee n evaluate d b y severa l investigator s an d wa s foun d t o perfor m well , wit h sensitivit y an d specificit y usuall y ove r 95%
a s compare d t o othe r invasiv e methods 18 " 21
. Give n th e usua l hig h sensitivit y o f PCR , thi s tes t ca n b e particularl y usefu l fo r th e post-treatmen t diagnosi s o f H. pylori, whe n th e bacteria l loa d ma y b e ver y low . However , i n severa l comparativ e studies , th e PC R tes t faile d t o detec t significantl y mor e treatmen t failure s tha n cultur e o r a combinatio n o f othe r conventiona l methods 3 - 22
. Owin g t o it s hig h sensitivity , PC R unfortunatel y carrie s a ris k o f fals e positiv e result s whic h ma y resul t eithe r fro m residua l H. pylori DN A o n th e fiberopti c endoscope s followin g inadequat e cleanin g an d disinfectio n o r fro m cross-contaminatio n durin g processin g o f specimen s i n th e laboratory 23
. A t present , PC R i s stil l technicall y demandin g an d no t generall y availabl e a s a routin e diagnosti c tool . Recently , however , methodo - logica l protocol s hav e bee n simplifie d an d improve d b y usin g hybrid - izatio n an d colorimetr y t o detec t th e amplificatio n products 24
. I t ca n b e anticipate d tha t PC R wil l b e use d mor e readil y i n routin e clinica l setting s onc e bein g full y automate d an d whe n commercia l kit s becom e available . I t i s als o likel y that , i n th e nea r future , PC R o r closel y relate d molecula r amplificatio n technique s wil l b e use d i n rapid tes t format s t o detec t antimicrobia l resistanc e (i.e. resistanc e t o macrolides ) t o H. pylori an d possibl y als o i n faece s t o contro l eradication .
Non-invasiv
e test s
Serology
H. pylori infectio n provoke s bot h loca l an d systemi c antibod y responses . Th e systemi c respons e typicall y comprise s a transien t ris e i n IgM , followe d b y a ris e i n specifi c Ig A an d Ig G maintaine d throughou t infection . A larg e numbe r o f kit s whic h detec t thes e antibodie s b y enzyme-linke d immunosorben t assa y (ELISA ) o r late x agglutinatio n hav e bee n develope d an d mos t clinica l laboratorie s ar e experience d i n performin g serologica l tests . Suc h test s mos t commonl y us e serum , althoug h detectio n o f Ig G i n urin e ha s als o prove d accurate 25
. Severa l commercia l o r in-hous e test s hav e bee n adapte d fo r us e o n saliva , but th e detectio n o f salivar y Ig A o r Ig G antibodie s ha s prove d overal l les s sensitiv e tha n serum-base d tests 26
- 27
. Th e performanc e o f differen t laborator y serologica l test s ha s bee n foun d t o var y appreciably . I n a larg e meta-analysis , severa l commercia l ELIS A kit s appeare d t o perfor m wel l wit h sensitivit y an d specificit y value s averagin g 90-95
% an d 80-90%
, respectivel y (Tabl e 1) . Th e
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Helicobacter infection
Tabl e 1 Comparativ e performanc e value s o f variou s H. Tes t Coba s Core *
Hellco-G
*
Malakit
*
GAPHgG
* Pylor i Stat * HM-CA P
Premie
r H. pylori
Pyloriset
* EI A G
Pyloriset
* EI A G *Brand name Roch e
Porton-Cambridg
e Biola b
Bio-Ra
d
Bio-Whlttake
r
Enteri
c Product s Os i Orio n (old ) Orio n (new )No. patient s 153
8 101
3 30
8 107
7 96
3 57
5 20 9 38
1 25
6No. scrie s 6 1 2 3 9 8 2 3 3
2pylori ELISA commercial kits
Sensitivit
y (% ) (average ) 93-9
9 (95 ) 71-9
6 (82 ) 87-9
6 (90 )
77-100(90
) 90-9
9 (96 ) 95-9
8 (97 ) 87-9
3 (89 ) 76-9
6 (91 ) 93-10
0 (97 )Specificity (%) (average ) 77-9
7 (88 ) 45-9
0 (70 ) 79-9
6 (86 ) 26-9
1 (63 ) 70-9
8 (90 ) 92-9
8 (93 ) 81-9
6 (88 ) 84-9
6 (86 ) 79-8
5 (83 ) - *Th e ne w versio n wa s introduce d i n 1995
. lowe r specificit y o f serologica l test s observe d i n certai n studie s ma y hav e largel y bee n explaine d b y th e inclusio n o f patient s previousl y treate d fo r H. pylori infectio n o r havin g receive d antibiotic s fo r th e treatmen t o f variou s intercurren t infections 21
. A combinatio n o f reliabl e referenc e method s need s t o b e applie d fo r evaluatio n o f test s an d difference s i n th e gol d standar d use d ma y als o hav e accounte d fo r som e o f th e difference s tha t hav e bee n observe d betwee n studies . Furthermore , difference s i n tes t accurac y ca n b e explaine d b y th e us e o f variou s antige n preparation s o r b y difference s i n infectin g strain s tha t resul t i n differen t immun e responses . Thi s ha s le d t o th e genera l recommendatio n tha t an y serologica l tes t fo r H. pylori shoul d b e validate d an d standardise d locall y befor e use . I n man y instances , thi s wil l impl y th e adjustmen t o f th e cut-of f value s recommende d b y th e manufacturer .
Numerou
s studie s hav e evaluate d th e performanc e o f a wid e rang e o f commercia l tests 2 ** 31
. I n mos t o f thes e reports , th e differen t test s per - forme d equall y well . Feldma n et aP l recentl y reporte d a multi-laborator y compariso n o f eigh t commerciall y availabl e H. pylori serolog y kits . A s show n i n Tabl e 2 , som e o f th e kit s produce d excellen t results . A numbe r o f rapi d serologica l offic e test s hav e recentl y bee n develope d fo r th e serodiagnosi s o f H. pylori infection 32
"* 0 . The y ar e base d o n a solid - phas e ELISA 32
- 3 3 o r o n late x agglutination 34
. On e majo r advantag e o f thes e test s ove r laborator y tests , i s tha t the y ca n b e applie d ver y easil y i n th e offic e o n whol e bloo d obtaine d b y fingerprick . Result s ar e availabl e o n sit e withi n 5-1 0 min , usuall y b y a simpl e colou r change , an d ther e i s n o nee d fo r an y specifi c equipment . I n a larg e meta-analysi s o f studie s publishe d i n th e literature , th e rapi d offic e test s overal l appeare d t o b e les s accurat e tha n th e laborator y tests , wit h sensitivit y an d specificit y value s averagin g 80-85
% an d 75-80%
, respectivel y (Tabl e 3) . I n som e studie s comparin g th e rapi d test s wit h onl y on e standard , th e sensitivit y result s wer e usuall y substantiall y better 32
. I n othe r reports 39
, th e 'office ' test s showe d poo r specificit y i n certai n populatio n ag e group s 18
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Practical diagnosis of H. pylori
Tabl e 2 Sensitivit y an d specificit y o f eigh t commercia l kit s teste d i n 1 7 laboratorie s o n identica l seru m sample s fro m 5 9 patient s (Optica l densit y value s i n th e gre y zon e wer e considere d negative ) Tes t Amra d Biola b
Bio-Ra
d Orio n Porto n Radi m Roch e
Whittake
rNo of laboratorie s 1 7 1 5 1 7 1 7 1 7 1 3 1 7 1
6Mean sensitivity
(SD ) 89.
4 (7.7 ) 79.
9 (9.1 ) 94.
9 (6.8 ) 95.
8 (3.9 ) 92.
3 (6.1 )
81.6(7.0
)
99.3(1.3
) 92.
9 (4.9 )Mean specificity (SD ) 93.
9 (9.7 ) 98.
6 (2.6 )
91.3(13.2
) 95.
5 (4.8 ) 87.
1 (12.6 )
90.7(17.6
) 86.
5 (5.2 )
89.4(11.1
) S D = standar d deviation : Adapte d from Feldma n et aP\ Tabl e 3 Performanc e value s o f variou s commercia l H. pylori rapi d test s ('office-base d tests' ) Tes t
Pylorise
t Dry *
Pylorise
t latex * Late x
FlexSure
*
Helisal
*
Immunocard
* Quic k Vue * CLOse rBrand nam e Orio n Diagnostic a Orio n Diagnostic a Oxoi d
SmithKlin
e Diagnostic s
Cortec
s
Meridia
n Diagnostic s Qulde l
Medica
l Instrument sNo patient s 34
8 93
2 20 2 116
9 78
8 7 8 72
7 8 6No serie s 3 8 1 5 5 1 3
1Sensitivity (%)
(average ) 80-9
7 (89 ) 60-9
2 (75 ) 8 6 74-9
5 (86 ) 82-9
2 (84 ) 9 2 82-9
9 (91 ) 9
5Specificity (S)
(average ) 77-8
5 (81 ) 50-7
6 (63 ) 7 5 69-8
9 (81 ) 56-9
1 (73 ) 9 8 52-9
2 (79 ) 7 2 (patient s ove r 4 5 year s o f age ) a s wel l a s i n som e ethni c group s (e.g. Sout h
Asians
) whil e the y performe d bette r i n som e othe r populatio n subgroup s (e.g. patient s les s tha n 4 5 year s o f ag e an d Europea n natives) . Moreover , problem s o f poo r readabilit y o f result s an d inter-observe r variation s i n interpretatio n o f result s wer e reporte d i n a notabl e proportio n o f case s (u p t o 10 % o f al l results ) i n som e studies 38
- 39
, whic h ma y limi t th e valu e o f certai n kits . Abov e all , i t i s importan t t o stres s tha t mos t reporte d evaluation s o f th e rapid office-base d serologica l test s hav e bee n undertake n i n a secondar y car e settin g an d i n patient s referre d fo r endoscopy . Ther e are , a t present , fe w report s o f th e evaluatio n o f thes e test s i n th e environmen t fo r whic h the y wer e designe d an d i t wil l b e particularl y importan t t o examin e th e result s obtaine d b y genera l practitioner s wh o wil l b e th e clinician s mos t likel y t o us e suc h screenin g devices . I n addition , i t wil l als o b e ver y importan t t o evaluat e th e short - an d long-ter m impac t tha t th e offic e serologica l test s ma y hav e o n th e clinica l managemen t o f patient s i n th e primar y car e setting .
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Immunoblo
t technique s als o sho w promise . Heterogeneit y ha s bee n observe d i n th e immun e response , bu t th e predictiv e valu e o f a give n ban d o r patter n fo r a specifi c patholog y i s stil l uncertai n an d it s useful - nes s i n patien t follow-u p ha s ye t t o b e determined 40
. However , som e studie s hav e show n tha t th e us e o f recombinan t antige n fo r cagA ma y b e valuabl e fo r predictin g th e presenc e o f pepti c ulce r diseas e i n a patient 41
. A s wit h th e ne w serologica l tests , furthe r wor k i s neede d t o establis h th e utilit y o f serologica l testin g fo r selectiv e pathogeni c strain s (e.g. cag A serology) , bu t i t ma y b e usefu l i n strategie s aime d a t narrowin g th e grou p o f patient s fo r who m H. pylori treatmen t shoul d b e considered . Urea breath tests Th e [ 13
C]-ure
a breat h tes t i s highl y sensitiv e an d specifi c fo r th e detectio n o f H. pylori infection . I n contras t t o serolog y whic h canno t alway s distinguis h betwee n pas t an d presen t infection , th e ure a breat h tes t i s a measur e o f curren t H. pylori infection . I t i s particularl y wel l suite d a s a follow-u p tes t i n th e earl y post-treatmen t perio d (4- 6 week s afte r en d o f therapy ) sinc e i t ha s a goo d predictiv e valu e fo r th e eradicatio n o f th e bacterium . I t i s a non-invasive , globa l tes t whic h i s eas y t o perfor m an d i s independen t o f transpor t condition s o r th e experienc e o f th e tester . Despit e thes e advantages , however , thi s tes t i s not ye t widel y availabl e an d i t i s stil l no t approve d i n man y Europea n countries . A comprehensiv e revie w o f th e ure a breat h test s i s presente d elsewher e i n thi s issue . Ke y point s fo r clinica l practic e • Wit h th e continuou s improvemen t o f diagnosti c techniques , th e availabilit y o f ne w diagnosti c test s an d th e efficac y o f moder n treatmen t regimen s i t i s t o b e expecte d tha t th e deman d fo r H. pylori testin g an d treatmen t initiate d a t a primar y car e leve l wil l als o increase . Severa l large-scal e comparativ e studie s hav e show n tha t invasiv e an d non - invasiv e test s performe d equall y well , wit h a sensitivit y an d specificity , i n th e rang e o f 90%
21>43
. I n practice , th e choic e o f a particula r tes t shoul d b e influence d b y loca l availabilit y an d expertise , a s wel l a s b y clinica l circumstances . • Th e hig h ureas e activit y o f H. pylori ca n b e use d a s a screenin g marke r o f infectio n i n patient s wh o presen t t o endoscop y wit h uppe r gastrointestina l symptoms . Th e newe r rapid ureas e stri p tests , whic h hav e bee n considerabl y improve d i n compariso n t o th e initia l ureas e 18 2 British Medical Bulletin 1998;5
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tests , ma y certainl y hel p th e endoscopis t i n decision-makin g a s t o whethe r o r no t therap y shoul d b e prescribed . Du e t o thei r lo w cost , thes e test s ar e th e endoscopi c test s o f choic e fo r initia l evaluation .
However
, the y shoul d b e use d i n additio n t o othe r invasiv e o r non - invasiv e test s (e.g. serology ) a s som e infecte d patient s ma y stil l b e misse d o n a n initia l screening . • Cultur e canno t b e recommende d fo r routin e evaluatio n o f H. pylori becaus e o f th e restricte d availabilit y o f goo d laborator y facilitie s an d th e man y potentia l error s involve d leadin g t o false-negativ e results .
However
, i t shoul d b e considere d whe n treatin g th e infectio n wit h a regime n tha t contain s drug s t o whic h H. pylori i s possibl y resistant .
Likewise
, cultur e shoul d b e favoure d afte r documente d treatmen t failur e o r i n patient s fro m a geographi c are a o r o f a n ethni c origi n wit h highe r likelihoo d o f antimicrobia l dru g resistance . PC R i s presentl y no t indicate d fo r us e i n th e routin e clinica l setting . However , th e rapid technologica l improvement s an d th e availabilit y o f commercia l kit s ma y rende r thi s techniqu e mor e readil y availabl e i n th e nea r future . • Th e ure a breat h test s ar e ver y accurat e fo r assessin g th e H. pylori statu s post-treatment . However , the y ar e stil l no t ye t widel y available .
Serolog
y ha s onl y limite d indicatio n fo r th e follow-u p afte r treatment .
Antibod
y titre s t o H. pylori var y markedl y betwee n infecte d individual s and , followin g successfu l treatment , tak e on e o r mor e year s t o retur n t o th e uninfecte d range , th e exac t tim e bein g dependen t o n th e hos t respons e an d o n th e tes t used . Rapi d offic e test s ar e no t quantitativ e an d ar e no t suitabl e fo r us e i n treatmen t follow-up . Whe n usin g quantitativ e ELISA , a 50
% decreas e i n Ig G titre s a t 6 month s ca n accuratel y predic t treatmen t success 43
. However , matche d pre - an d 6 mont h post-treatmen t seru m sample s ar e needed , an d preferabl y shoul d b e ru n togethe r t o avoi d inter-batc h variation . Thi s seem s difficul t t o appl y routinel y becaus e collectin g an d storin g pre-treatmen t specimen s ma y b e problemati c i n clinica l practic e an d als o becaus e 6 month s i s a lon g tim e t o wai t fo r results . • O n th e othe r hand , serologica l H. pylori screenin g appear s particularl y attractiv e a s a pre-endoscop y o r a s a pre-treatmen t screenin g i n youn g dyspepti c patient s (age d les s tha n 4 5 years ) withou t alar m symptoms . Suc h recommendation s ar e supporte d b y a recen t
Europea
n consensu s repor t o n curren t concept s o n th e managemen t o f H. pylori infection 44
. However , th e feasibilit y o f algorithm s base d o n serologica l H. pylori statu s an d ag e wil l greatl y depen d o n th e incidenc e o f specifi c gastroduodena l pathologie s i n differen t population s a s wel l a s o n th e performance s o f th e screenin g tests . Screenin g test s wit h optima l
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sensitivit y woul d absolutel y b e require d i f use d t o selec t suitabl e group s o f patient s fo r endoscop y withou t missin g significan t disease . • Conversely , test s yieldin g a hig h specificit y woul d b e necessar y i n orde r t o avoi d givin g unnecessar y eradicatio n therap y t o non-infecte d patients . Som e o f th e ne w offic e serologica l test s currentl y availabl e ma y not appea r sufficientl y accurat e t o fulfi l thes e requirements . Furthe r researc h i s clearl y neede d i n orde r t o delineat e th e plac e tha t rapi d H. pylori serologica l test s ma y hav e i n a primar y car e environment . Th e cost-effectivenes s an d clinica l consequence s o f differen t serology-base d strategie s shoul d als o b e establishe d an d ma y b e foun d t o diffe r betwee n countrie s wit h differen t healthcar e system s an d differen t economi c constraints .
References
1 Marshal l BJ , Warre n JR . Unidentifie d curve d bacill i i n th e stomac h o f patient s wit h gastriti s an d pepti c ulceration . Lancet 1994
; i : 1311-
5 2 NI H Consensu s Developmen t Panel . Helicobacter pylon i n pepti c ulce r disease . JAMA 1994
; 272
: 65-
9 3 va n Zwe t AA , Thij s JC , Roosendaa l R , Kuiper s EJ , Pen a S , d e Graaf f J . Practica l diagnosi s o f
Helicobacter
pylori infection . Eur J Gastrocnterol Hepatol 1996
; 8 : 501-
7 4 Yousf i MM , El-Zimait y HM , Col e RA , Gent a RM , Graha m DY . Detectio n o f Helicobacter pylon b y rapi d ureas e tests : i s biops y siz e a critica l variable ? Gastromtest Endosc 1996
; 43
: 222 -
4 5 Lain e L , Chu n D , Stei n C , El-Beblaw i I , Sharm a V , Chandrasom a P . Th e influenc e o f siz e o r numbe r o f biopsie s o n rapi d ureas e tes t results : a prospectiv e evaluation . Gastrointest Endosc 1996
; 43
: 49-5
3 6 Wo o JS , El-Zimait y HMT , Gent a RM , Yousf i MM , Graha m DY . Th e bes t gastri c sit e fo r obtainin g a positiv e rapi d ureas e test . Helicobacter 1996
; 4 : 256-
9 7 Malfertheine r P , Dominguez-Muno z J , Heckenmulle r H , Neubran d M , Fische r HP , Sauerbruc h T . Modifie d rapi d ureas e tes t fo r detectio n o f Helicobacter pylori infection . Eur J Gastroenterol
Hepatol
1996
; 8 : 53-
6 8 Lain e L , Lewi n D , Naritok u W , Estrad a R , Cohe n H . Prospectiv e compariso n o f commerciall y availabl e rapi d ureas e test s fo r th e diagnosi s o f Helicobacter pylori. Gastrointest Endosc 1996
; 44
: 523-
6 9 Puet z T , Vaki l N , Phadin s S , Dun n B , Robinso n J . Th e Pylorite k an d th e CL O test : accurac y an d incrementa l cos t analysis . Am ] Gastroenterol 1997
; 92
: 254 -
7 1 0 Yousf i MM , El-Zimait y HM , Gent a RM , Graha m DY . Evaluatio n o f a ne w reagen t stri p rapi d ureas e tes t fo r detectio n o f Helicobacter pylori infection . Gastrointest Endosc 1996
; 44
: 519-2
2 1 1 Megrau d F . Diagnosti c bacteriologiqu e standar d d e l'infectio n a H. pylori. In : Megrau d F ,
Lamouliatt
e H . (eds ) Helicobacter pylori, Vol 1: Epidemiologie patbogenie, diagnostic. Paris :
Elsevier
, 1996
; 250-6
6 1 2 Glupczynsk i Y . Cultur e o f Helicobacter pylori fro m gastri c biopsie s an d antimicrobia l susceptibilit y testing . In : Le e A , Megrau d F . (eds ) Helicobacter pylori: Techniques for Clinical
Diagnosis
and Basic Research. London : W B Saunders , 1996
; 17-3 2 1 3 Roosendaa l R , Kuiper s EJ , Pen a AS , d e Graaf f J . Recover y o f Helicobacter pylori fro m gastri c biops y specimen s i s not dependen t o n th e transpor t mediu m used . / Clm Microbiol 1995
; 33
:
2798-80
0 1 4 Ha n SW , Flam m R , Hache m C Y et al. Transpor t an d storag e o f Helicobacter pylori fro m gastri c mucosa l biopsie s an d clinica l isolates . Eur J Clm Microbiol Infect Dis 1995
; 14 : 349-5
2 1 5 Hache m CY , Clarridg e JE , Evan s DG , Graha m DY . Compariso n o f aga r base d medi a fo r primar y isolatio n o f Helicobacter pylori. J Clin Pathol 1995
; 48
: 714-
6 18 4 British Medical Bulletin 1998,5
4 (No . 1 )Downloaded from https://academic.oup.com/bmb/article/54/1/175/265759 by guest on 27 July 2023
Practical diagnosis of H. pylori
16 . Fresnadill o Martine z MJ , Rodrigue z Rinco n M , Blazque z d e Castr o A M et al. Comparativ e evaluatio n o f selectiv e an d non-selectiv e medi a fo r primar y isolatio n o f Hclicobacter pylori fro m gastri c biopsies . Helicobacter 1997
; 2 : 36 -
9 1 7 Jonker s D , Stobbering h E , Stockbrugge r R . Influenc e o f oropharyngea l flor a an d specime n pre - treatmen t o n th e recover y o f Helicobacter pylori. Eur ] Clin Microbiol Infect Dis 1996
; 15 : 378-8
2 1 8 Lag e AP , Godfroi d E , Fauconnie r A et al. Diagnosi s o f Helicobacter pylori infectio n b y PCR : compariso n wit h othe r invasiv e technique s an d detectio n o f cagA gen e i n gastri c biops y specimens . / Clin Microbiol 1995
; 33
: 2752-
6 1 9 Bass o D , Navagli a F , Cassar o M et al. Gastri c juic e polymeras e chai n reaction : a n alternativ e t o histolog y i n th e diagnosi s o f Helicobacter pylori infection . Helicobacter 1996
; 1 : 159-6
4 2 0 Li n SY , Jen g YS , Wan g C K et al. Polymeras e chai n reactio n diagnosi s o f Helicobacter pylori i n gastroduodena l diseases : compariso n wit h cultur e an d histopathologica l examinations . /
Gastroenterol
Hepatol 1996
; 11 : 286-
9 2 1 Thij s JC , va n Zwe t AA , Thij s W J et al. Diagnosti c test s fo r Helicobacter pylori: a prospectiv e evaluatio n o f thei r accuracy , withou t selectin g a singl e tes t a s th e gol d standard . Am ]
Gastroenterol
1996
; 91
: 2125-
9 2 2 Godfroi d E , Mans y F , Fauconnie r A et al. Post-treatmen t diagnosi s o f H. pylori infectio n b y PCR : a compariso n wit h othe r invasiv e technique s [abstract] . Gut 1996
; 3 9 (Suppl . 2) : A11 3 2 3 Roosendaa l R , Kuiper s EJ , va n de n Brul e A J et al. Importanc e o f th e fiberopti c endoscop e cleanin g procedur e fo r detectio n o f Helicobacter pylori i n gastri c biops y specimen s b y PCR . / Clin Microbiol 1994
; 32
: 1123-
6 2 4 Lag e AP , Fauconnie r A , Burett e A et al. Rapi d colorimetri c hybridizatio n assa y fo r detectin g amplifie d Helicobacter pylori DN A i n gastri c biops y specimens . / Clin Microbiol 1996
; 34
: 530-
3 2 5 Alemohamma d MM , Fole y TJ , Cohe n H . Detectio n o f immunoglobuli n G antibodie s t o
Helicobacter
pylori i n urin e b y a n enzym e immunoassa y method . / Clin Microbiol 1993
; 31
: 2174-
7 2 6 Luzz a F , Malett a M , Imene o M et al. Salivary-specifi c immunoglobuli n G i n th e diagnosi s o f
Helicobacter
pylori infectio n i n dyspepti c patients . Am J Gastroenterol 1995
; 90
: 1820-
3 2 7 Fallon e CA , Elizo v M , Clelan d P et al. Detectio n o f Helicobacter pylori infectio n b y saliv a Ig G testing . Am] Gastroenterol 1996
; 91
: 1145-
9 2 8 va n d e Wou w BA , d e Boe r WA , Jans z AR , Royman s RT , Staal s AP . Compariso n o f thre e commerciall y availabl e enzyme-linke d immunosorben t assay s an d biopsy-dependen t diagnosi s fo r detectin g Helicobacter pylori infection . / Clin Microbiol 1996
; 34
: 94-
7 2 9 Meije r BC , Thij s JC , Kleibeuke r JH , va n Zwe t AA , Berrelkam p RJ . Evaluatio n o f eigh t enzym e immunoassay s fo r detectio n o f immunoglobuli n G agains t Helicobacter pylori. J Clin Microbiol 1997
; 35
: 292-
4 3 0 Marchildo n PA , Ciot a LM , Zamaniya n FZ , Peacoc k JS , Graha m DY . Evaluatio n o f thre e commercia l enzym e immunoassay s compare d wit h th e I3 C ure a breat h tes t fo r detectio n o f
Helicobacter
pylori infection . / Clin Microbiol 1996
; 34
: 1147-5
2 3 1 Feldma n RA , Deck s JJ , Evan s SJ . Multi-laborator y compariso n o f eigh t commerciall y availabl e
Helicobacter
pylori serolog y kits . Helicobacter pylori serolog y Stud y Group . Eur } Clin
Microbiol
Infect Dis 1995
; 14 : 428-3
3 3 2 Graha m DY , Evan s J r DJ , Peacoc k J , Bake r JT , Schrie r WH . Compariso n o f rapi d serologica l test s (FlexSur e H P an d QuickVue ) wit h conventiona l ELJS A fo r detectio n o f Helicobacter pylori infection . Am] Gastroenterol 1996
; 91
: 942-
8 3 3 Moayyed i P , Carte r AM , Catt o A , Heppe l RM, Gran t PJ , Axo n ATR . Validatio n o f a rapi d whol e bloo d testin g fo r diagnosin g Helicobacter pylori infection . BMJ 1997
; 314
: 11 9 3 4 Lozniewsk i A , D e Korwi n JD , Conro y MC , Plena t F , Webe r M . Evaluatio n o f Pylorise t Dry , a ne w rapi d agglutinatio n tes t fo r Helicobacter pylori antibod y detection . / Clin Microbiol 1996
; 34
: 1773-
5 3 5 Jone s R , Phillip s I , Feli x G , Tai t C . A n evaluatio n o f near-patien t testin g fo r Helicobacter pylori i n genera l practice . Aliment Pharmacol Ther 1997
; 11 : 101-
5 3 6 Reill y TG , Poxo n V , Sander s DS , Elliot t TS , Wal t RP . Compariso n o f serum , salivary , an d rapi d whol e bloo d diagnosti c test s fo r Helicobacter pylon an d thei r validatio n agains t endoscop y base d tests . Gut 1997
; 40
: 454-
8
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Medical Bulletin 1998;5
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3 7 Sadowsk i D , Cohe n H , Lain e L et al. Evaluatio n o f th e Flexsur e H P fingerstic k bloo d tes t fo r th e detectio n o f Helicobacter pylori infectio n [abstract] . Gastroenterology 1996;
110
: A24 6 3 8 Ston e MA , Mayberr y JF , Wick s AC B et al. Nea r patien t testin g fo r Helicobacter pylori: a detaile d evaluatio n o f th e Cortec s Helisa l rapi d bloo d test . Eur J Gastroenterol Hepatol 1997
; 9 : 257-6
0 3 9 Che n TS , Chan g FY , Le e SD . Serodiagnosi s o f Helicobacter pylori infection : compariso n an d correlatio n betwee n enzyme-linke d iramunosorben t assa y an d rapi d serologica l tes t results . / Clin Microbiol 1997
; 35
: 184-
6 4 0 Nilsso n I , Ljung h A , AJeljun g P , Wadstro m T . Immunoblo t assa y fo r serodiagnosi s o f
Helicobacter
pylori infections . / Clin Microbiol 1997
; 35
: 427-3
2 4 1 Cove r TL , Glupczynsk i Y , Lag e A P et al. Serologi c detectio n o f infectio n wit h cagA *
Helicobacter
pylori strains . / Clm Microbiol 1995
; 33
: 1496-50
0 4 2 Cutle r AF , Havsta d S , M a CK , Blase r MJ , Perez-Pere z GI , Schuber t TT . Accurac y o f invasiv e an d noninvasiv e test s t o diagnos e Helicobacter pylori infection . Gastroenterology 1995
; 109
: 136-4
1 4 3 Hirsch l AM , Brandstatte r G , Dragosic s B et al. Kinetic s o f specifi c Ig G antibodie s fo r monitorin g th e effec t o f anti-Hehcobacter pylori chemotherapy . / Infect Dis 1993
; 168
: 763 -
6 4 4 Malfertheine r P , Megrau d F , O'Morai n C et al. [Europea n Helicobacter pylori Stud y Grou p (EHPSG)] . Curren t Europea n concept s i n th e managemen t o f Helicobacter pylori infectio n - Th e Maastrich t Consensu s Repor t (Review) . Gut 1997
; 41
: 8-1 3 18 6 British Medical Bulletin 1998;5
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