The GBS: pro screening

1

Pierrette Melin

Pierrette Melin

Medical

Medical microbiologymicrobiology University

University hospitalhospital of of LiegeLiege Belgian

Belgian referencereference laboratorylaboratory for GBSfor GBS

“

“

The GBS

_{The GBS}

”

_”

PRO

PRO

SCREENING

SCREENING

2

“

“EvidenceEvidence--basedbased””

Prevention of

Prevention of

perinatal

perinatal

Group B

Group B

streptococcal infections

streptococcal infections

Guidelines from Belgian Council of Hygiene

Guidelines from Belgian Council of Hygiene-- July 2003July 2003

Gynecologists

Gynecologists--obstetriciansobstetricians Pediatrician

Pediatrician--neonatologistsneonatologists Microbiologists

Microbiologists French/

French/ FlemishFlemish University

University//nonnon--universityuniversity

Foulon W. Foulon W. Hubinont Hubinont C.C. Lepage Lepage P.P. Levy Levy J.J. Mahieu Mahieu L.L. Alexander S. Alexander S. Beckstedde Beckstedde I.I. Claeys Claeys G.G. De Mol P. De Mol P. Donders Donders G.G. http:// http://www.health.fgov.bewww.health.fgov.be/CSH_HGR/CSH_HGR General Recommendations General Recommendations

& Specific suggestions & Specific suggestions

WORKING GROUP :

WORKING GROUP :

Secr

Secr.: Dubois JJ, CSH.: Dubois JJ, CSH

Melin Melin P.P. Naessens Naessens A.A. Potvliege Potvliege C.C. Temmerman Temmerman M.M. Tuerlinckx Tuerlinckx D.D. Van Eldere J. Van Eldere J.

3

Gyneco

Gyneco--ObstetriciansObstetricians

Laboratory Laboratory microbiologist microbiologist Pediatricians Pediatricians Labor

Labor//deliverydelivery WardWard

Intrapartum

Intrapartum

antimicrobial

antimicrobial

prophylaxis

prophylaxis

Universal

Universal

prenatal

_prenatal

screening

_screening

at

_at

35

₃₅

-

-37

37

weeks

weeks

gestation

gestation

Risk

Risk--basedbased approachapproach reservedreserved for for womenwomen withwith unknownunknown GBS

4

Why

Why

IAP ?

IAP ?

Why

Why

a

a

Screening

Screening

-

-

based

based

approach

approach

?

?

_Risks

_Risks

_{for GBS EOD}

_{for GBS EOD}

_Goals

_Goals

_of

_of

_IAP

_IAP

_{Effectiveness}

_{Effectiveness}

_Belgian

_Belgian

_choice

_choice

_Concerns

_Concerns

_{about use}

_{about use}

_of

_of

_prophylaxis

_prophylaxis

_Concerns

_Concerns

_about

_about

_number

_number

_of

_of

candidates for IAP

candidates for IAP

5

GBS VERTICAL TRANSMISSION

GBS VERTICAL TRANSMISSION

GBS VERTICAL TRANSMISSION

GBS

GBS colonizedcolonized mothersmothers

Non-colonized newborns Colonized newborns 40 40 -- 60 %60 % 2 2 -- 4 %4 % GBS EOD GBS EOD 60 60 -- 40 %40 % 96 96 -- 98 %98 % Asymptomatic Asymptomatic sepsis sepsis pneumonia pneumonia meningitis meningitis long

long termterm sequelae sequelae _CDC Risk Risk factors factors

6

GBS

GBS

maternal

_maternal

colonization

_colonization

Risk

Risk

factor

factor

for

for

early

early

-

-

onset

onset

disease

disease

(EOD)

(EOD)

:

:

vaginal GBS

vaginal GBS

colonization

colonization

at

at

delivery

delivery

_{GBS carriers GBS carriers}

_{10 10 -- 30 % of 30 % of womenwomen}

_{ClinicalClinical signssigns not not predictivepredictive}

_{DynamicDynamic conditioncondition}

_{PrenatalPrenatal cultures cultures latelate in in pregnancypregnancy cancan predictpredict}

delivery

7

Additional Risk Factors

for Early-Onset GBS Disease

Obstetric factors: Obstetric factors:



 Prolonged rupture of membranes, Prolonged rupture of membranes, 

 Preterm delivery, Preterm delivery, 

 IntrapartumIntrapartum feverfever



GBS GBS bacteriuriabacteriuria



Previous infant with GBS diseasePrevious infant with GBS disease



Immunologic: Immunologic:



 Low specific Low specific IgGIgG to GBS capsular to GBS capsular polysaccharide

polysaccharide

No difference in occurrence either in GBS

No difference in occurrence either in GBS

Positive or Negative women, except

Positive or Negative women, except

intrapartum

intrapartum feverfever

Lorquet S., Melin P. & al.

Lorquet S., Melin P. & al.

J

8

GBS EOD

GBS EOD

-

_-

Belgian data

Belgian data

_{IncidenceIncidence}

_{1985: 3/1000 live births1985: 3/1000 live births}

_{1990: 3 cases + 4 likely cases/1000 live births 1990: 3 cases + 4 likely cases/1000 live births}

_{1999, estimation : 2/1000 live births 1999, estimation : 2/1000 live births}

_{Meningitis : 10 %Meningitis : 10 %}

_{Mortality > 14 %Mortality > 14 %}

60 % EOD

_{60 % EOD}

: WITHOUT any

_{: WITHOUT any}

maternal/obstetric risk factor

maternal/obstetric risk factor

_{Prenatal screeningPrenatal screening}

_{RectoRecto--vaginal cultures : 13vaginal cultures : 13--25 % GBS Positive25 % GBS Positive} P. Melin, 2001

9

Prevention

Prevention

of

_of

perinatal

_perinatal

GBS EOD

_{GBS EOD}

_{IntrapartumIntrapartum antibioticsantibiotics}

_{HighlyHighly effective effective atat preventingpreventing EOD EOD in in womenwomen atat riskrisk}

of

of transmittingtransmitting GBSGBS to to theirtheir newbornsnewborns ( ( >> 4 h)4 h)

INTRAPARTUM ANTIMICROBIAL

INTRAPARTUM ANTIMICROBIAL

PROPHYLAXIS (

PROPHYLAXIS (

IAP

IAP

)

)

_{Main goal}

_{Main goal}

_{To To preventprevent 70 to 80 % 70 to 80 % ofof GBS EO casesGBS EO cases}

_{SecondarySecondary ::}

10

How best to

How best to

identify women

identify women

at risk ?

at risk ?

35--37 37 wkswks ScreeningScreening--basedbased strategystrategy Or

Or

Risk

11 0 0,5 1 1,5 2 2,5 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 Year Early-onset Late-onset

Impact of prevention practices

Impact of prevention practices

Rate of Early

Rate of Early

-

-

and Late

and Late

-

-

onset GBS

onset GBS

Disease in the 1990s, U.S.

Disease in the 1990s, U.S.

Consensus Consensus guidelines guidelines Group B Strep Group B Strep Association Association formed formed

1st ACOG & AAP

1st ACOG & AAP

statements statements CDC draft CDC draft guidelines published guidelines published S.

12

Screening

Screening

for GBS

for GBS

or

or

risk

risk

-

-

factors

factors

?

?

P.Melin

P.Melin, 40th ICAAC, 2000, 40th ICAAC, 2000 L.Mahieu

L.Mahieu, 2000, J , 2000, J ObstObst GynGyn;5:460;5:460--44

90 44 0 20 40 60 80 100 Screening-based % O b st e tr ic ia ns French C. Flemish C.

13

Effectiveness

Effectiveness

of

_of

both

_both

CDC 1996

_{CDC 1996}

approaches

approaches

Schrag

Schrag S. et alS. et al. N . N EnglEngl J J MedMed 2002; 347:2332002; 347:233--99

“

“

RF

RF

”

”

easier and cheaper than

easier and cheaper than

“

“

screening

screening

”

”

BUT

BUT

_{PopulationPopulation--based surveillance study, U.S. based surveillance study, U.S.}

_{312 GBS EOD ; > 600 000 live births 312 GBS EOD ; > 600 000 live births}

_{AUDIT AUDIT (5144 files)(5144 files): : «« IAP given when mandatoryIAP given when mandatory »»}

_{52 % 52 % ofof allall deliveriesdeliveries hadhad screeningscreening}

_{IAP IAP givengiven more more oftenoften if if «« GBS Positive GBS Positive screeningscreening »»}

than

than if if presencepresence of >= 1 RFof >= 1 RF

“

14

Why

Why

is

is

Screening

Screening

more

more

protective

protective

than

than

the

the

risk

risk

-

-

based

based

approach

approach

?

?

Broader

Broader

coverage

coverage

of

of

«

«

at

at

-

-

risk

risk

»

»

population

population



 _{CapturesCaptures colonizedcolonized womenwomen withoutwithout} obstetric

obstetric RFRF 

 _{HighHigh levellevel of of compliancecompliance withwith} recommendations

recommendations 

 _{EnhancedEnhanced compliancecompliance withwith riskrisk--basedbased} approach

approach cannotcannot preventprevent as as manymany cases cases as

15

CDC

CDC

& RF reserved for & RF reserved for unknown GBS culture unknown GBS culture

results results

Endorsed

Endorsed by AAP by AAP and

and by ACOGby ACOG in 2002

16

Screening

Screening

-

-

based

based

strategy

strategy

for

for

prevention

prevention

of GBS

of GBS

perinatal

perinatal

disease

disease

Recto-vaginal GBS screening culture at 35-37 weeks of gestation For ALL pregnant women

Recto-vaginal GBS screening culture at 35-37 weeks of gestation

For ALL pregnant women

> 1 Risk factor: - Intrapartum fever > 38°C*** - ROM > 18 hrs > 1 Risk factor: - Intrapartum fever > 38°C*** - ROM > 18 hrs

Intrapartum prophylaxis NOT indicated

IN T R A P A R T U M A N T IB IO P R O P H Y L A X IS IN D IC A T E D Neg

Neg PosPos

if NO

if NO if YESif YES

Unless patient had a previous infant with GBS invasive disease or GBS bacteriuria during current pregnacy or delivery occurs < 37 weeks’ gestation *

GBS GBS NegNeg if YES if YES GBS POS GBS POS

Not done, incomplete or unknown GBS result

! Facultative !

! Facultative !

Intrapartum

17

Prenatal

Prenatal

GBS

_GBS

screening

_screening

:

_:

Laboratory

Laboratory

procedure

_procedure

35

35--37 wks37 wks V+RV+R

Selective enrichment broth (eg.LIM)

Overnight, 35

Overnight, 35--3737°°CC

Sub-culture onto “Granada” agar

Overnight, 35

Overnight, 35--3737°°C C anaerobicallyanaerobically

POSITIVE screening Negative screening

Presence Presence of orange of orange colonies colonies = GBS = GBS Absence of orange colonies Minimum Minimum::

18

What

What

to do in case of Positive

_{to do in case of Positive}

GBS

GBS

screening

screening

?

?

_Send

_Send

_results

_results

_to

_to

_requesting

_requesting

_doctor

_doctor

and

and

a copy to

a copy to

expected

expected

site for

site for

delivery

delivery

DO NOT

_{DO NOT}

treat

_treat

during

_during

pregnancy

_pregnancy

if

_if

asymptomatic

asymptomatic

( ! To _{( ! To} treat_treat if GBS _{if GBS} bacteriuria_bacteriuria ! )_{! )}

19

Feasibility

Feasibility

in Belgium

_{in Belgium}

_Screening

_Screening

_{FollowFollow--upup visitvisit alreadyalready scheduledscheduled aroundaround} 35

35--37 37 wkswks gestationgestation

_{AccessabilityAccessability to to laboratorieslaboratories}

_IAP

_IAP

20

Concerns

Concerns

about

_about

potential

_potential

adverse /

adverse /

unintended

unintended

consequences

consequences

of

_of

prophylaxis

_prophylaxis

_{Allergies Allergies}

_{AnaphylaxisAnaphylaxis occursoccurs but but rarelyrarely}

_{Changes in incidence or resistanceChanges in incidence or resistance of of otherother} pathogens

pathogens causingcausing EODEOD

_{Data are Data are complexcomplex ……}

_{BUT Most BUT Most studiesstudies: stable rates of : stable rates of «« otherother »»}

sepsis

sepsis

Changes in GBS _{Changes in GBS} antimicrobial_{antimicrobial} resistance_resistance profile

21

Concerns

Concerns

about

_about

potential

_potential

adverse /

adverse /

unintended

unintended

consequences

consequences

of

_of

prophylaxis

_prophylaxis

Management of

_{Management of}

neonates

_neonates

_{IncreaseIncrease of of unecessaryunecessary evaluationevaluation}

_{IncreaseIncrease of of unecessaryunecessary antimicrobialantimicrobial} treatments

22

Management of

Management of

neonates

_neonates

at

_at

risk

risk

for GBS EOD

for GBS EOD

Rem.

Rem.: 95 % : 95 % ofof GBS EOD are GBS EOD are symptomaticsymptomatic < 24 h < 24 h ofof livelive

Neonates

Neonates

born

born

to

to

women

women

who

who

received

received

IAP

IAP

Symptomatic

Symptomatic NN NN

/

/

At

At lowlow//atat highhigh riskrisk .

To

To minimizeminimize unnecessaryunnecessary evaluationevaluation andand antimicrobial

23

Concerns

Concerns

about

_about

the

_the

number

_number

of

_of

women

women

who

_who

are

_are

given

_given

IAP

_IAP

Prevalence

Prevalence ofof factorsfactors inducinginducing thethe decisiondecision ofof IAP IAP (CHR

(CHR LiegeLiege, 2002, 1350 , 2002, 1350 consecutiveconsecutive deliveriesdeliveries))

/ 19 % 1.6 % 15-25 % / / GBS Positive ROM >= 18 h T° >= 38°C 17 % 1.2 % Prematurity GBS bacteriuria « RISK FACTORS » OPTION « SREENING » OPTION FACTORS Lorquet,

24

Perinatal

Perinatal

GBS

GBS

disease

disease

burden

burden

_Neonatal

_Neonatal

_illness

_illness

_/

_/

_death

_death

_,

_,

_Long

_Long

_-

_-

_term

_term

_disability

_disability

_Maternal

_Maternal

_morbidity

_morbidity

Neonatal

25 +/ +/-- 250250 << 50 % << 50 % 166 166 / / N N €€ x 166x 166 +/ +/-- 3,300 3,300 €€ n not ot estimatedestimated** +/ +/-- 250250 75 % 75 % 111 111 2,200 2,200 €€ N N €€ x 111x 111 +/ +/-- 3,300 3,300 €€ not

not estimatedestimated**

Patients

Patients treatedtreated/1000/1000 birthsbirths GBS cases

GBS cases preventedprevented (%)(%)

Patients

Patients treatedtreated//preventedprevented case

case

Lab

Lab costcost //preventedprevented casecase IAP

IAP costcost //preventedprevented casecase Min.cost

Min.cost /case /case (8 d, ICU/NN)(8 d, ICU/NN)

Indirect

Indirect costcost, , sequelaesequelae, , etcetc

PRM >= 18 h, PRM >= 18 h, T T°°>=38>=38°°CC GBS + GBS + Criteria

Criteria for IAPfor IAP

RF options

RF options

Screening

Screening optionoption

Hypothesis

Hypothesis: GBS : GBS prevalenceprevalence in in womenwomen: 20% ; : 20% ; NaturalNaturalincidence incidence ofofGBS EOD: 3/1000 ; GBS EOD: 3/1000 ; prevalence

prevalence ofof RF as in RF as in ourourstudystudy in in LiegeLiegein 2002in 2002

* If

* If additionaladditional costcost/case > 4500 /case > 4500 €€, , ScreeningScreening isis costcost effective versus RFeffective versus RF

Rough

26 0 10 20 30 40 50 60 1999 2000 2001 2002 2003 2004 N o s tr a in s EOD LOD Belgian consensus CDC CSH Surveys & feed-back Strains

Strains isolatedisolated fromfrom neonatalneonatal EOD or LOD EOD or LOD andand sent to

27

Conclusions & perspectives

Conclusions & perspectives

Prevention

Prevention

of GBS

of GBS

perinatal

perinatal

Diseases

Diseases

PRO

PRO

-

-

SCREENING

SCREENING

Currently

Currently

the

the

best choice

best

choice

but

but

NOT

NOT

the

the

ideal

ideal

strategy

strategy

Temporary

Temporary, , waitingwaiting for vaccines, for vaccines, otherother approachapproach

_{To To implementimplement in in thethe dailydaily practicepractice}

_{V+R V+R ScreeningScreening methodmethod}

28

Key GBS Resources

Key GBS

Key GBS

Resources

_Resources

_{MMWR : MMWR : August 16, 2002 / 51(RR11); 1August 16, 2002 / 51(RR11); 1--2222}

_{ACOG ACOG CommComm OpinOpin 2002, N2002, N°°279279}

_{ObstetObstet GynecolGynecol, 2002;100:1405, 2002;100:1405--1212}

_{CDCCDC ’’s GBS Internet pages GBS Internet page}

_{http://http://www.cdc.govwww.cdc.gov//groupBstrepgroupBstrep//}

_{Conseil supConseil supéérieur drieur d’’hygihygièène ne (brochure (brochure strepstrep B)B)}