mullany: saving lives with 4% chlorhexidine cleansing of the umbilical cord

7/28/2019 Mullany: Saving Lives With 4% Chlorhexidine Cleansing of the Umbilical Cord

1/27

S

av

ingl

iveswit

h4

.0%

chlorhex

idin

ec

leans

ingof

the

umb

ilica

lco

rd

Luke

C.

Mu

llany,

PhD

,MHS

Assoc

iateProf

essor,

Jo

hns

Hop

kinsU

nivers

ity

(lm

ullany

@jhsp

h.e

du

)

Joha

nnes

burg,

-Apri

l2013


2/27

Infect

ionrepres

entsasignificantca

use

ofneonatalmor

talityinlo

wresource

settin

gs

Exposuretopathogensis

highatbi

rth

andim

mediatepostpartum

Umbilicalcordvesselsareopenfor

24-

48ho

ursafterb

irth

Stumpisrapidlycolonized

Infec

tionan

dum

bilica

lcord


3/27

TopicalAntisepticsan

dtheCord

~50yearsago:n

earlyunive

rsaluseof

topica

lantisepticsinfacilitiesofhigh

incom

ecountries

~25-40yearsago

:MANYstudieson

topica

lantisepticstoexamine:

Topicalantisepticsreduceexposuretopathogens

Less

directeviden

ceforreductionininfection/

death

Bylat

e1990s,largeliterature,

butalmost

NONE

fromplaceswithhighinfection

risk


4/27

WHOGu

idelines

Recognizingalackofclea

revidence,

WHO

provided3keyrecommendations:

1.

Prom

otekeepingthecor

dclean/d

ry

2.

Topicalantisep

ticcouldbeused

whereinfection/exposureriskishigh

3.

Rese

archneed

edforopt

imal

guidelinesforhighrisks

ettings

*WHO.

Careoftheumbilicalcord.

WHO.

Genev

a,

1998.

WHO/RHT/MSM98

.4


5/27

Why

Ch

lorhexi

dine

?

Broad

spectrum

antisepticsolution

Readilyavailable,worldwide

Excellentsafety

record

Superiortoman

yotherch

oicesfor

reduc

ingcordp

athogens

WHO

ModelListofEssentialMedici

nes

forco

rdcleansing

Evide

nceforreductionof

mortality


6/27

O

verv

iew

an

dPoo

led

Ana

lysis

ofCHX

Tria

ls


7/27

SarlahiDistrict,

Nepal:2002-2006

Mullanyetal,Lancet2006

Sylhe

tDistrict,Banglades

h:2007-20

09

Arifeenetal,La

ncet2012

Sindh

Province,

Pakistan:2008-2009

Soo

fietal,Lancet2012

SAsiaCHXCord

Clean

sing

Tria

ls


8/27

Exclusion

No

tmet

within

10days

after

birt

h

No

tmet

within

7days

after

birt

h

No

tmet

within

3days

after

birth

Con.

an

oma

lies

Ove

rallDes

ignand

Contex

t

Instu

dyarea,

attimeo

fs

tudy

Nep

al

Bangla

des

h

Pak

istan

OverallNMR

32/1

000

36/1

000

30/

1000

%HomeBirths

92%

88%

80

%

No.

Clusters(av

gsize)

413(700)

133(4

000)

187(

1000)

Eligibility

Allliveb

irths

in

study

area

Allliveb

irths

in

study

area

Alllive

births

in

studyarea


9/27

In

terven

tion

Pro

vide

d

Bangla

des

h

Pak

istan

ComparisonGroup

InterventionGroups

CHXConcentra

tion

Nep

al

Dry

Cor

dCare

1.

Mu

ltip

leCHX

2.

Soap/

H2

O

4.0%

Dry

Cor

dCare

1.

Mu

ltip

leCHX

2.

Single

CHX

4.0

%

FreqofMultiple

App

1,2,3,4,

6,8,1

0

1,2,3,4

,5,6,7

InterventionPro

vider

Loca

lpro

jec

t

staff

Localp

rojec

t

sta

ff

Dry

Co

rdCare

1.

Multip

leCHX

2.

Hand

Was

hing

3.

HW+

CHX

4.0%

Da

ily

for

14days

TBAtocare

taker


10/27

Co-int

erven

tion

s,

Ou

tco

mes,

SS,

FU

Nep

al

Bangla

des

h

Pak

istan

PrimaryOutcom

es

Morta

lity

Ompha

litis

Morta

lity

Omph

alitis

Mor

tality

Omp

ha

litis

SampleSizeTotal

15,1

23

29,7

60

9,741

SampleSizePe

rGroup

~5050

~9,9

00

~4,8

50

FollowUpDays

1,2,3,4,6,

8,1

0,1

2,

14

,21

,28

1,3,6,9,1

5,2

8

1,3,5,

7,1

4,2

8

Basicinterventionsto

allbabies/moth

ers

CDK

,Fe/FA

,TT

,

promot

iono

f

ANC/E

NC

,

CDK,F

eFA

promotio

no

fTT

,

ANC,

ENC

Bas

icco

mpo

f

ENCaspromo

ted

by

MoH


11/27

Impac

ton

All-Cause

Morta

lity

Nepal

24%lowermortalitya

t28days(mu

ltipleCHX)

34%lowermortalityifinitiatedwithin24hours

NoimpactofSoap/H2

Ocleansing

Banglade

sh

20%lowermortalitya

t28days(sin

gleCHX)

6%lowermortalityat

28days(multipleCHX,

NS)

Strongevidenceofim

pactamongp

retermbabies

Pakistan

38%lowermortalitya

t28days(CH

Xgroups)


12/27

Prel

iminary

Poo

led

Ana

lys

is

M

ORTALITY:

AnyCHXvs

.NoCHX

Study

Overa

ll

0.7

7(0

.63

,0.94)

RR(95%

CI)

RR(95%

CI)

1

.5

.75

1.2

Nepal

0.7

6(0.5

8,1.

00)

Bangladesh

0.8

8(0.7

4,1.

04)

Pakistan

0.6

2(0.4

5,0.

85)

M

ORTALITY:AnyCHXv

s.

NoCHX

23%re

duction

inmortalityamong

thosereceivinginte

rvention


13/27

Impac

ton

Cord

In

fec

tion

Inallst

udies

Multiple

CHXreducedcordin

fection

Nepal:

33%75

%reduction

Bangladesh:

15%45

%reduction

Pakistan:

40%50

%reduction


14/27

Poole

dAnalysisCordInfection

SevereInfectio

n:AnyCHX

vs.

NoCHX

Pakistan

Study

Nepal

Banglades

h

0.5

1(0.1

8,

1.45

)

RR(95%CI)

0.2

5(0.1

3,

0.51

)

0.5

5(0.3

0,

1.01

)

0.5

1(0.1

8,

1.45

)

RR(95%CI)

0.2

5(0.1

3,

0.51

)

0.5

5(0.3

0,

1.01

)

1

.1

.25

.5

1

1.5

C

ordInfectio

n:AnyCHX

vs.

NoCHX

0.4

1(0.2

4,

0.69

)

Overall

59%

reductio

ninser

iouscor

d

infect

ionamo

ngthosereceiving

chlo

rhexidin

e


15/27

Exposur

eo

fthecords

tum

p

Loca

ls

ignso

f

infec

tion

No

loca

ls

igns

ofinfe

ction

Dea

th

B

loo

ds

tream

infec

tion

No

bloo

ds

tream

infec

tion

Surv

iva

l

Surv

iva

l

Mu

llanye

ta

l,PIDJ

,2009

Corde

xposure

an

dcaus

alpa

thw

ays


16/27

Sum

maryo

fMo

de

ofActio

n

0

D

ay

7

14

Preventcontinu

ed

exposurew

ith

repeatapplicatio

ns

Co

lon

iza

tion

ofthepa

ten

t

vesse

ls

Seps

is

Dea

th

Visible

infec

tion

Sepsis

Dea

th

Earlyapplications

protectduring

patentperiod

CHXApp

lica

tion

Mortality

Risk

HIGH

MEDIUM

LOWER

Primary

benefitof

earlyCHX

clea

nsings

Additionalbenefit

ofm

ultiple

cleansing

Segre

J,S

ep

tem

ber

2011


17/27

CommonQuestions/Though

ts

Ischlo

rhexidine

safe?

Yes,chxhasbeenincommo

nusefor60

years,andhase

xcellentsafe

tyrecord.No

repo

rtedadverseeventswhe

nusedon

umb

ilicalcord

Ischlo

rhexidine

readilyav

ailable?

Yes,oneofthemostcommo

nlyusedtopical

antisepticsinthe

world


18/27

Puttingchlorhex

idineonthecordmight

delayseparationtime

TRU

Eanyactionthatkeep

sthecord

clea

ner,willd

ela

ycordseparationtime

This

isimportantfromaprog

rammatic

experienceandforshapinga

cceptance

Wha

tismoreimportant?

savinglivesand

reducinginfec

tionOR

Havecordfalloffonday5inst

eadofday6?


ts


19/27

Doesn

tcleanan

ddrycord

carework

justas

well?

Allthreeoftheb

igtrialstellu

stheopposite

Therearenocommunity-bas

edrandomiz

ed

trialsofpromotionofdryandcleancord

prac

ticesshowingimpacton

mortality

Why

not?Becausekeeping

cordcleana

nd

avoidingpathogensisveryd

ifficult(~80%

-

90%

ofcordscolonizedimmediately)


ts


20/27

Wewo

ntbenefitfromchlo

rhexidine

becaus

eharmful

practicesarenolonger

commo

n

Not

necessarilytrue.

Thecordstumpisstill

exposedtopathogensthroug

hroutineho

me

and

facilitypract

ices

Amo

ngbabiesw

herecaretakersfollowed

suggestedcleanedcordpra

ctices,

chlo

rhexidinestillreducedinfectionand

mortality


ts


21/27

Thisint

erven

tionwou

ldon

lyhe

lpba

bies

bo

rn

athome

Nottrue.

Facilitybo

rnbabiesinth

eBangladesh

and

Nepaltrialshad:

Lo

wermortalityifth

eygotchlorhexid

ine

Lo

werriskofcordinfection

Reducedcolonizationofthecord

andsamerelatio

nshipbetweencordseparationtim

eand

co

rdcare,asseen

inhomebirths

facilitiesalsostruggletoachievehygienicpractices

babiesaredischargedintosameenvironmentas

home-bornbabies


ts


22/27

Com

monQ

ues

tion

s/Po

int

s

Cantwejustusealcohol,

gentianviolet,

oriodin

e?

Alco

holnotgood

forpreterm

skin

Gen

tianvioletno

tsufficiently

bacteriocida

l

Iodinetooeasily

absorbedth

roughskin

Allh

ighqualitye

videncefrom

community-

settingsisbased

onchlorhex

idine


23/27

ThepriorWHOre

commenda

tionwas

clean/drycordcare!

Whe

nmakingthe

recommenda

tion,

WHO

reco

gnizedthat:

Evidencefromhig

her-riskpopulationswasnotav

ailable

M

oreresearchwa

sneededtodefineoptimalcordcare

Topicalantiseptic

suchaschlorhexidinecouldbe

used

ifexposuretothe

cordwaslikely

Asp

ublichealthp

rofessionalsweareobligatedto

updaterecommen

dationsandpoliciesifevid

ence

eme

rgesthatwarrantschange


ts


24/27

Promo

tionofchlorhexidineconflicts

withou

rprevious

messages..

Mes

sagescanb

eshapedto

fitconsistently

with

promotiono

fcleancord

care

Topicalchlorhex

idinecanbe

promotedasa

tooltohelpcare

takersachie

veacleanc

ord

Eve

nifconflict,

thisisNOT

avalidrea

son

forINACTION,iftheeviden

ceexists.


ts


25/27

Final

Thoug

hts

CHXissafe,acceptable

CHXcanhavev

ariousformulations,

packa

ging,

distributionm

odels

Clean

singshou

ldbeginasearlyas

possi

bleafterb

irth

CHXcordclean

singcans

avehundr

eds

oftho

usandsoflives,atv

erylowco

st


26/27

P

artners

an

dSu

pport

Nepal:

NNIPS,

JHU,

IOM-TribhuvanUnive

rsity,

NICHD,

Bill&

Melinda

GatesFound

ation,

USAID,

Proctorand

Gamble

,MoHP,

NepalFamilyHealthProject

Banglade

sh:

MoHFW

,ICDDR,B,J

HU,

Shimantik,

DSH,

SNL/S

ave

TheCh

ildren(USA),USAID,

ThrasherResearch

Fund

Pakistan:

AgaKh

anUniversity,

JohnSnowIn

c,

PakistanM

oH


27/27

CHXre

duc

escolo

niza

tion

Largereduc

tionsin

colonization

duringthe

periodofop

en,patent

bloodvesse

ls

Multipleclea

nsing

sustainsthe

reduction

throughfirst

weekoflife

mullany: saving lives with 4% chlorhexidine cleansing of the umbilical cord

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