strongyloidiasis a review of diagnosis

8/12/2019 Strongyloidiasis a Review of Diagnosis

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Strongyloides

A Neglected Tropical Disease

A Review of Diagnosis

Dr Harsha Sheorey Clinical Microbiologist

St Vincent’s Hospital, Melbourne



Clinical presentations

Asymptomatic carriers (maority! – Reactivation wit" immunosuppression

Acute infection – Cutaneous # larva currens – Ab$ominal # %& symptoms (uncommon!

C"ronic infection wit" vague ab$osymptomsHyperinfection'ife t"reatening % sepsis)meningitis



When is diagnosis/screeningindicated

Acute)recent infection – 'arva currens or une*plaine$ eosinop"ilia, urticarial or

serpiginous s+in lesions – Diarr"oea)%& symptoms)ulmonary symptoms in people

from en$emic areas – -ne*pecte$)une*plaine$ invasive % sepsis)meningitis

C"ronic infection – Refugees)migrants)resi$ents. of en$emic areas

– o/, past e*posure in en$emic areas, sanitation wor+ers &mmunosuppresse$)H0'V12)un$ergoing

immunosuppression)transplant)c"emot"erapy3ollow up of treatment

* Including Indigenous Australians



Acute infection

C " r

o n i c

i n f e c t i o

n



What’s available fordiagnosis

4osinop"ilia Microscopy (faeces, ot"er! Culture (faeces, ot"er!

Histology 4n$oscopy Ra$iology Serology Intradermal skin tests Copro-antigen Molecular diagnosis

otroutinelyavailable

Requenq-Mendez et al !"#S $%D &an '()+ , ). e'(



What are the issues indiagnosis

Most met"o$s are insensitive – Variable e*cretion – 4ggs not present in faeces – &ne*perience – 3res" specimen usually not

available-se of Serology is not well

5stan$ar$ise$’Many ot"er met"o$s are non1



Eosinophilia (or IgElevels)

on1specific # ot"er parasites 0ransient # only in migratory p"ase

'ow V for intestinal parasites intravellers from en$emic areas (6278!an$ 69:8 in pe$iatric refugees

&f positive, coul$ be a potential mar+er of

Strongyloi$iasis in t"e rig"t groups



Eosinophiliaarasites that cause Eosinophilia

!vervie" – 4osinop"ilia is a reaction to

tissue invasive stages of"elmint" (worm! infection;

– 0wo proto<oans, Cystisospora,an$ Sarcocystis, rarely cause amil$ eosinop"ilia;

– 0"e following "elmint" infectionscause eosinop"ilia, in travelersor ot"erwise;

#pecific Infections – $re%uent and !ften

Intense (=7,::: eos)>'!?

● Strongyloides (absentin compromise$ "osts!

● 'ymp"atic filariasis(especially tropicalpulmonary

eosinop"ilia!● %o/ocara (visceral

&oderate During 'arval &igrationAbsent or &ild During Chronic Infections – Ascaris

– Hoo+worm – 0asciola

– Clonorchus

– !aragonimus

–

#pisthorchis !ccurs at *arious #tages of infection

– Schistosoma – Cysticercosis – 1chinococcus (especially if cyst rupture occurs! – %richuris – Angiostrongylus – #nchocerca – "oa – 2nathastoma – Capillaria – 0asciolopsis – %richostrongylus – 3aylisascaris – @t"er "uman an$ non1"uman filarias (Diro4ilaria5

Mansonella! – Anisakis



#peci+en for D, ofStrongyloidis

3aeces – 3res" (not refrigerate$!

– Several (sensitivity increases wit"numbers!

Respiratory spec? sputum, A'Duo$enal aspirate? 4ntero1string

test, en$oscopyCS3 1 rare



&icroscop-

'oo+ for rab$itiform larvaeB eggs note*crete$

Hig"ly specific ($)$ from Hoo+wormlarvae!'ow sensitivity

– intermittent s"e$$ing – tec"nical e*perience

4asier if motile – fres" specimen, not refrigerate$ – wit"out preservative



/et rep of $uo$enalcontents

Rha6diti4orm lar7ae

/et rep of plate culture orin "yperinfection syn$rome

0ilari4orm lar7ae



Culture (concentration)

3res" specimen reuire$Various tec"niues

–

aermann’s – Hara$a1Mori’s – Agar plate – /ater emergence met"o$ – C"arcoal culture

ot $oneroutinely



.aer+ann’s techni%ue

Most sensitive(cf AC!

'abourintensivemessyEC"ances of

lab infection



3ilter paper

3aeces specimen

'arvae migrate

towar$s water

/ater

3alcon tube

arada0&ori culture

Close$system

Relativelyeasy to setup

'ess

sensitiveSuperse$e$

by AC



Agar plate culture (AC)no" the preferred techni%ue



Endoscop-

Any segment of %& involve$on1specific unless larvae)a$ult seen

-lceration (apt"oi$, eryt"ematous,serpigenous!, blee$ing, pustule li+elesions (F larvae burying!

mucosal oe$ema, $uo$enal spasms,t"ic+ene$ fol$s, brown $iscoloration,yellowis" no$ules



istolog-

Hig"ly specificSections of larvae or a$ults

(occasionally eggs!Mainly in $uo$enum or gastric

crypts4osinop"ilic infiltrates in lamina

propia # $irectly relate$ tointensity



Histology (HG4!



1adiolog-

on1specific fin$ingsHig"ly variable

– ormal appearance of %&0 – Mil$ e$ema wit" t"ic+ene$ fol$s o"

mucosa

– Significant $ilatation – Stricture (best seen wit" arium

Swallow!



Intra0der+al s2in test

-sing somatic an$ 4S antigensCross reactions wit" ot"er

nemato$esersists after successful

treatment'ower sensitivity in H0'V12 an$

ot"er immunosuppressionDifficult to perform an$ rea$



#erolog-

Various met"o$s use$? &3A0, &HA, %A0, 4&A, /,

'&S – 4&A? An optic $ensity (@;D;! I :;J is consi$ere$

negative, w"ile @;D K :;7 is consi$ere$ positiveB

interme$iate values are recor$e$ as in$eterminate

Various antigens use$ # variable sensitivity an$

specificity –

Cross reacts wit" ot"er nemato$es Hig"ly variable response

– 4*act time of sero1conversion not clearly $efine$

– Varies wit" stage)severity of infection # wi$e variation

– %enerally "ig"er in pts from en$emic areas #

EIA



Table 34 Characteristics of the +ain serological tests for strong-loidiasis4

Reuena1MLn$e< A, C"io$ini , isoffi , uonfrate D, et al; (J:2N! 0"e 'aboratory Diagnosis an$ 3ollow -p ofStrongyloi$iasis? A Systematic Review; 'oS egl 0rop Dis O(2!? eJ::J; $oi?2:;2NO2)ournal;pnt$;:::J::J"ttp?))www;plosnt$;org)article)info?$oi)2:;2NO2)ournal;pnt$;:::J::J

http://www.plosntd.org/article/info:doi/10.1371/journal.pntd.0002002

http://www.plosntd.org/article/info:doi/10.1371/journal.pntd.0002002



'uciferase I++uno0recipitation #-ste+ 'I#

'&S assay was $evelope$ base$ on immunoglobulin &g %antibo$y to a N2+D recombinant Strongyloides antigen(&4! an$ was compare$ wit" an &4 en<yme1lin+e$immunosorbent assay (4'&SA!; A secon$ antigen, Sstercoralis immunoreactive antigen (Ss&R!, was teste$

alone an$ in combination wit" &4; purifie$ easily an$ pro$uce$ in large amounts '&S involves fusion of a protein antigen to t"e en<yme

reporter Renilla luciferase (Ruc!, e*pression of t"e Ruc1antigen fusion in mammalian C@S cells, immobili<ation of

t"e Ruc1antigen fusion on protein bea$s, an$ uantitationof antigen1specific antibo$y by t"e a$$ition of acoelentera<ine substrate an$ t"e measurement of lig"tpro$uction

generates values wit" substantial separation between

negative an$ positive antibo$y responses P'&S (uic+)rapi$! "as been $esigne$



Copro0antigen

4'&SA on faeces'ittle cross reaction

4asy an$ ine*pensiveetter wit" formalin1treate$

faeces

More "uman stu$ies reuire$



&olecular diagnosis

Several R01CRs $esigne$ 0argets # 2Qs rRA an$ JQs rRA

Directly on faecesSpecificity an$ sensitivity $epen$s onnumber of larvae (severity ofinfection! (cf AC! – 62::8 in en$emic areas – Role in low inci$ence countries unclear

Multiple* (up to O parasites! $esigne$



$ollo" up of treat+ent

3aeces micro not reliable – negative $oes not cure – e*crete$ intermittently

AC better # multiple over one yearSerology most suitable currently

– Abs fall ta+es between 21J years (mini m!?$epen$s on initial titre (en$emic = non1en$emic!

– S"oul$ be $one in same lab wit" same met"o$,preferably in parallel

– o uniform international criteria)o reliable cut1off – Ratio T:; ($ivi$e postR* titre by preR* titre!



Current #creening 5Issues

Serology (Ueosinop"ilia! – o stan$ar$isation (antigen, +its! – ot" @0 sensitive)specific enoug"

– 4&A "as no titre an$ very narrow range3res" faeces for AC

– 3res" specimen $ifficult to get ($istances! – Multiple reuire$

● 9 6Q:8 sensitivity● O 62::8 sensitivity

Combination # i$eal

4/AR4



&nterme$iate)in$eterminate may be an

issue

'oa G Cs"oul$ berule$ out

'oa G Cs"oul$ berule$ out

3res"Multiple

samples maybe necessary

3res"Multiple

samples maybe necessary

4/AR4 may

ta+e 2Jmt"s

4/AR4

Variable

4/AR4Variable

(4&A?@D!

4*pect$efinite$rop

F AC *9



(

4nglWM

e$J:2

NBNSQ?e27

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yper1infection Syn$rome in a Vietnamese man on steroi$s for %iant cell arteriti

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http://www.nejm.org/toc/nejm/368/12/

http://www.nejm.org/toc/nejm/368/12/



D R A

3 0 efore immunosuppression

3rom)been in en$emicarea or $oubtful

"istory

3rom non1en$emicarea or no "istory of

e*posure

Serology U AC*9 Serology

ot"NE6ATI*

E

4it"er!#ITI*

E

Continue "ith i++unosuppression

!#ITI*E

NE6ATI*E

%reat 8ith

I7ermectin

AC*9

!#ITI*E

NE6ATI*E

4P-&V@CA'

AC Agar late Culture on fres" faec

1ule out Loaloa7 and

pregnanc-

. "oa "oa en$emic in /estern an$ Central Africa

6et +orehistor-

4veryone

V X

Repeat testing after immunosuppression? Fever N mt"s

ibl



ossible $uture#creening/tests

'&S wit" &4 (in place of 4&A! – More sensitive)specific t"an 4&A)&3A0)&HA

CR (possibly uantitative! – Multiple*e$ wit" ot"er parasites

Copro1antigen in faeces (in place ofAC! – Can be $one on preserve$ faeces

Combination 1 i$eal



TAN8 9!:;

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strongyloidiasis a review of diagnosis

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