evidence to recommendations table · the recommendation applies to specific contexts, in specific...
TRANSCRIPT
Page 1 of 29
Evidence to Recommendations Table
Question: Should the currently available whole cell, killed Oral cholera vaccines (OCVs) be recommended for use among persons ≥1 year old (Shanchol/Euvichol/mORCVax) or ≥ 2 years old (Dukoral), including pregnant women in different cholera endemic, epidemic/outbreak and humanitarian emergency settings? Population: Individuals in different cholera endemic, epidemic/outbreak and humanitarian emergency settings. Intervention: Killed, whole-cell oral cholera vaccines Comparison: Placebo/no vaccination/other prevention and control measures (e.g. WASH) Outcome: Cases of cholera Background: Cholera, an acute watery diarrheal disease, caused by toxigenic strains of the bacterium Vibrio cholerae O1 and O139, causes an estimated over 2.9 million cases and over 95,000 deaths annually in cholera endemic countries alone and frequent epidemics in other settings with poor water and sanitation infrastructure. Global estimates range from 1.4 –4.8 million cases and 28,000 – 142,000 deaths every year. The disease is characterized by acute onset watery diarrhea leading to rapid dehydration and death, if not promptly treated with fluid replacement and antibiotics for severe cases. Pregnant women are especially vulnerable from the dehydrating effects of cholera. OCVs have been available since the 1990s and have been recommended previously by WHO (most recent position statement of 2010). Since 2010, large scale epidemics and surges in endemic cholera have continued to occur and have been compounded by multiple humanitarian emergency situations. In 2013, a global oral cholera vaccine stockpile was established. Several additional studies and evaluations have been conducted of OCV use in different endemic, outbreak and humanitarian emergency settings. Additional data is now available to review evidence for recommendations. CRITERIA JUDGEMENTS RESEARCH EVIDENCE ADDITIONAL INFORMATION
PROB
LEM
Is the problem a priority?
No Probably No
Uncertain Probably Yes
Yes Varies
Cholera remains a significant public health problem globally. Global estimates range from 1.4 –4.8 million cases and 28,000 – 142,000
The global burden has significantly increased as a result of humanitarian emergencies (conflict situations, natural disasters and
Page 2 of 29
deaths every year. An estimated 2.9 million cases of cholera annually in 69 cholera endemic countries and 95,000 deaths during 2008–2012. Pregnant women are especially susceptible to adverse outcomes for themselves and the fetuses as a result of rapid dehydration. Cholera most often occurs among impoverished populations with limited access to health care resources.
environmental factors such as the El Nino phenomenon).
Are a large number of people affected?
No Probably No
Uncertain Probably Yes
Yes Varies
Global estimates range from 1.4 –4.8 million cases and 28,000 – 142,000 deaths every year. An estimated 2.9 million cases of cholera annually in 69 cholera endemic countries and 95,000 deaths during 2008–2012. In 2015, over 172,454 cases and 1,304 deaths were reported to the WHO by 42 countries with an overall case-fatality rate (CFR) of 0.8% (several countries reported high case fatality rates).
The reported numbers are largely underreported due to several factors – inadequate surveillance, fear of impact on trade and tourism etc.
BEN
EFIT
S &
HAR
MS
OF T
HE
OPTI
ONS
Are the desirable anticipated effects large?
No Probably No
Uncertain Probably Yes
Yes Varies
The vaccines have been shown to be efficacious and effective in multiple settings. Additional data showing herd protection effects is also available. However, data on the actual impact on disease transmission is limited.
The impact is dependent on factors such as vaccine coverage. Data on coverage in most settings show that vaccination campaigns have been feasible and acceptable.
Are the undesirable anticipated effects small?
No Probably No
Uncertain Probably Yes
Yes Varies
Safety of the vaccines has been demonstrated in several different settings.
Page 3 of 29
What is the overall certainty of this evidence?
No included studies Very low Low Moderate High
28
Moderate to high level of evidence. In addition to the 28 studies included in the systematic review, there are several other evaluations and observational studies that corroborate these findings.
VALU
ES
How certain is the relative importance of the desirable and undesirable outcomes?
Important uncertainty
or variability
Possibly important
uncertainty or
variability
Probably no
important uncertainty
or variability
No important
uncertainty or
variability
No known undesirable outcomes
Vaccines have been shown to be safe and effective in multiple settings. No major adverse events have been demonstrated.
Are the desirable effects large relative to undesirable effects?
No Probably No
Uncertain Probably Yes
Yes Varies
RESO
URCE
USE
Are the resources required small?
No Probably No
Uncertain Probably Yes
Yes Varies
A global OCV stockpile was established in 2013 and is financially supported by Gavi, the Vaccine Alliance. Gavi also provides funding for operational costs of vaccination campaigns. The resources required to conduct vaccination activities have varied based on the setting.
Vaccines are available through the Gavi-supported stockpile. Additionally, manufacturers are working to reduce the cost of vaccine to a more affordable pricing.
Is the incremental cost small relative to the net benefits?
No Probably No
Uncertain Probably Yes
Yes Varies
Several costing and cost-effectiveness studies have showed that cholera vaccination is cost-effective at the current vaccine pricing in high burden settings.
There is emphasis also on ensuring the OCVs are integrated into overall country and regional level cholera control plans.
Page 4 of 29
EQUI
TY
What would be the impact on health inequities?
Increased Probably increased
Uncertain Probably reduced
Reduced Varies
This disease affects mainly populations in poor-resource settings with limited clean water, sanitation and hygiene. The intervention would reduce health-inequities across populations.
ACCE
PTAB
ILIT
Y
Is the option acceptable to key stakeholders?
No Probably No
Uncertain Probably Yes
Yes Varies
Since the establishment of the OCV stockpile in 2013, over 7 million doses have been used in over 14 countries in multiple endemic, outbreak, and humanitarian emergency situations, and requests have been made by country-level stakeholders to the International Coordinating Group (ICG). Therefore, it is assumed that the option is acceptable to key stakeholders.
Which option is acceptable to target group? Intervention Comparison
Both Neither Unclear
Multiple evaluations of vaccine coverage and knowledge, attitudes and practices have been conducted which have shown that vaccination has been feasible and acceptable in multiple settings.
FEAS
IBIL
ITY
Is the option feasible to implement?
No Probably No
Uncertain Probably Yes
Yes Varies
The option will likely be feasible to implement in most settings, though limited access in the context of natural disasters or armed conflict may impede immediate implementation.
Balance of consequences
Undesirable consequences
clearly outweigh desirable consequences
in most settings
Undesirable consequences probably
outweigh desirable consequences
in most settings
The balance between desirable and undesirable
consequences is closely balanced or
uncertain
Desirable consequences probably outweigh
undesirable consequences
in most settings
Desirable consequences clearly outweigh
undesirable consequences in most settings
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Type of recommendation
We recommend against the option
We suggest considering the option
Only in the context of rigorous research
Only with targeted monitoring and evaluation
Only in specific contexts
We recommend the option
The recommendation applies to specific contexts, in specific (sub)
populations and in conjunction with other prevention and control
measures.
Recommendation
Given the current availability of prequalified whole-cell, killed, oral cholera vaccines (OCVs) and data on their safety, efficacy, field effectiveness, feasibility, impact and acceptability in cholera-affected populations, these vaccines should be used in areas with endemic cholera, in humanitarian crisis with high risk of cholera and during cholera outbreaks, in conjunction with other cholera prevention and control strategies such as appropriate case management, WaSH interventions, surveillance and community mobilization. Based on available evidence, there are considerable benefits and very few risks for including pregnant women in OCV vaccination campaigns.
Implementation considerations
Mass vaccination campaigns are usually the most practical option for delivering oral cholera vaccines. Schools, religious institutions and other community settings can be appropriate venues for vaccination campaigns using fixed sites. Outreach activities can also be organized. Incorporating cholera vaccination with other vaccination activities can be an alternative or complementary strategy to mass campaigns.
Planning for campaigns should be done in a timely manner so vaccines can be used as soon as they arrive in country. It’s beneficial to use vaccines as early as possible in outbreak situations.
Monitoring and evaluation Monitoring and evaluation activities should be conducted to document experiences and understanding vaccine impact.
These are also critical to be done if newer vaccines or newer delivery strategies are implemented.
Page 6 of 29
Research priorities It is important to perform systematic economic analyses to measure intervention cost, cost effectiveness and cost benefit in different settings where campaigns have been conducted.
Additional research is needed to better inform number of doses, optimal dosing interval (dose spacing) and issues related to duration of protection in different settings. More information is needed on the effectiveness in children 1—5 years old.
Further assessment of herd protection is needed.
There is a need to further work on methodologies to measure the impact of vaccination by better defining relevant and meaningful comparison groups and identify standardized indicators across geographies and settings.
Alternative delivery strategies such as self-administration, outside-the-cold-chain (CTC / ECTC), linking OCV with other health interventions should be further evaluated in a large variety of settings.
More information is needed on co-administration of OCV with other vaccines, especially with oral vaccines such as oral polio vaccine and rotavirus vaccine.
Page
7 o
f 29
A
pp
en
dix
3:
Sum
mar
y o
f Ev
ide
nce
GR
AD
E Ta
ble
s
Safe
ty in
gen
eral
po
pu
lati
on
P
op
ula
tio
n: N
on-p
regn
ant a
dults
and
chi
ldre
n ≥
1 ye
ar o
ld (S
hanc
hol/E
uvic
hol/m
ORC
Vax)
or ≥
2 y
ears
old
(D
ukor
al)
Inte
rven
tio
n: 2
dos
es o
f the
cur
rent
ly a
vaila
ble
kille
d, w
hole
-cel
l ora
l cho
lera
vac
cine
s (O
CVs)
C
om
par
iso
n: P
lace
bo o
r no
vacc
ine/
oth
er p
reve
ntio
n an
d co
ntro
l mea
sure
s (e.
g. w
ater
, san
itatio
n an
d hy
gien
e (W
ASH)
) O
utc
om
e: S
erio
us A
dver
se E
vent
s Fol
low
ing
Imm
uniza
tion
Wha
t is t
he e
vide
nce
that
the
curr
ently
ava
ilabl
e ki
lled,
who
le-c
ell O
CVs a
re sa
fe a
mon
g no
n-pr
egna
nt
indi
vidu
als (
Duko
ral ≥
2 y
ears
old
, Sha
ncho
l/Eu
vich
ol/m
ORC
Vax
≥ 1
year
old
s)?
Ra
ting
Adju
stm
ent t
o Ra
ting
Qua
lity
of
Evid
ence
No.
of s
tudi
es/s
tart
ing
ratin
g 10
RCT
1 4
Fact
ors
decr
easin
g co
nfid
ence
Lim
itatio
n in
stud
y de
sign
No
serio
us
0 In
cons
isten
cy
No
serio
us
0 In
dire
ctne
ss
No
serio
us
0 Im
prec
ision
N
o se
rious
0
Publ
icat
ion
Bias
N
o se
rious
0
Fact
ors
Incr
easin
g Co
nfid
ence
Larg
e ef
fect
N
ot a
pplic
able
0
Dose
-res
pons
e N
ot a
pplic
able
0
Anta
goni
stic
bia
s and
co
nfou
ndin
g N
ot a
pplic
able
0
Fina
l num
eric
al ra
ting
of q
ualit
y of
evi
denc
e 4
Sum
mar
y of
Fin
ding
s
Stat
emen
t on
qual
ity o
f evi
denc
e
Evid
ence
supp
orts
a
high
leve
l of c
onfid
ence
th
at th
e tr
ue e
ffect
lies
cl
ose
to th
at
of th
e es
timat
e of
the
effe
ct o
n th
e he
alth
ou
tcom
e.
Conc
lusio
n
High
leve
l of s
cien
tific
ev
iden
ce th
at th
e ris
k of
se
rious
adv
erse
eve
nts
follo
win
g im
mun
izatio
n w
hen
usin
g th
e cu
rren
tly li
cens
ed O
CVs
is lo
w.
1 In a
dditi
on to
the
rand
omize
d co
ntro
lled
tria
ls, se
vera
l fie
ld st
udie
s (fie
ld e
ffect
iven
ess a
nd c
over
age
surv
eys)
hav
e ev
alua
ted
the
occu
rren
ce o
f adv
erse
eve
nts a
nd th
e fin
ding
s of t
hese
stud
ies s
uppo
rt th
e hi
gh le
vel o
f evi
denc
e fr
om th
e ra
ndom
ized
cont
rolle
d tr
ials
used
for g
radi
ng fo
r saf
ety
outc
omes
.
Page
8 o
f 29
R
efe
ren
ces
1.
Co
ncha
A e
t al.
Safe
ty a
nd im
mun
ogen
icity
of o
ral k
illed
who
le c
ell r
ecom
bina
nt B
subu
nit c
hole
ra
vacc
ine
in B
arra
nqui
lla, C
olom
bia.
Bul
l Pan
Am
Hea
lth O
rgan
199
5; 2
9(4)
:312
-321
. 2.
Tr
ach
DD e
t al.
Inve
stig
atio
ns in
to th
e sa
fety
and
imm
unog
enic
ity o
f a k
illed
ora
l cho
lera
vac
cine
de
velo
ped
in V
iet N
am. B
ull P
an A
m H
ealth
Org
an 2
002;
80(
1):2
-8.
3.
Anh
DD e
t al.
Safe
ty a
nd im
mun
ogen
icity
of a
refo
rmul
ated
Vie
tnam
ese
biva
lent
kill
ed, w
hole
-cel
l, or
al c
hole
ra v
acci
ne in
adu
lts. V
acci
ne 2
007;
25(
6):1
149-
1155
. 4.
M
ahan
abal
is D
et a
l. A
Rand
omize
d, P
lace
bo-C
ontr
olle
d Tr
ial o
f the
Biv
alen
t Kill
ed, W
hole
-Cel
l, O
ral
Chol
era
Vacc
ine
in A
dults
and
Chi
ldre
n in
a C
hole
ra E
ndem
ic A
rea
in K
olka
ta, I
ndia
Plo
sOne
200
8;
3(6)
: e23
23.
5.
Sur D
et a
l. Ef
ficac
y an
d sa
fety
of a
mod
ified
kill
ed-w
hole
-cel
l ora
l cho
lera
vac
cine
in In
dia:
an
inte
rim a
naly
sis o
f a c
lust
er-r
ando
mise
d, d
oubl
e-bl
ind,
pla
cebo
-con
trol
led
tria
l. La
ncet
200
9; 3
74:
1694
-170
2.
6.
Saha
A e
t al.
Safe
ty a
nd im
mun
ogen
icity
stud
y of
a k
illed
biv
alen
t (O
1 an
d O
139)
who
le-c
ell o
ral
chol
era
vacc
ine
Shan
chol
, in
Bang
lade
shi a
dults
and
chi
ldre
n as
you
ng a
s 1 y
ear o
f age
. Vac
cine
20
11; 2
9(46
): 82
85-8
295.
7.
Q
adri
F et
al.
Feas
ibili
ty a
nd e
ffect
iven
ess o
f ora
l cho
lera
vac
cine
in a
n ur
ban
ende
mic
sett
ing
in
Bang
lade
sh: a
clu
ster
rand
omise
d op
en-la
bel t
rial.
Lanc
et 2
015;
386
:136
2-13
71.
8.
Desa
i SN
.et a
l. A
Rand
omize
d, P
lace
bo-C
ontr
olle
d Tr
ial E
valu
atin
g Sa
fety
and
Imm
unog
enic
ity o
f th
e Ki
lled.
Biv
alen
t, W
hole
-Cel
l Ora
l Cho
lera
Vac
cine
in E
thio
pia.
Am
. J. T
rop.
Med
. Hyg
201
5, 9
3(3)
: 52
7–53
3 9.
Ba
ik Y
O e
t al.
A ra
ndom
ized,
non
-infe
riorit
y tr
ial c
ompa
ring
two
biva
lent
kill
ed, w
hole
cel
l, or
al
chol
era
vacc
ines
(Euv
icho
l vs S
hanc
hol)
in th
e Ph
ilipp
ines
. Vac
cine
201
5; 3
3(46
): 63
60-6
365.
10
. Qad
ri et
al.
Effic
acy
of a
Sin
gle-
Dose
, Ina
ctiv
ated
Ora
l Cho
lera
Vac
cine
in B
angl
ades
h. N
Eng
l J M
ed
2016
: 374
: 172
3-32
.
Page
9 o
f 29
Sa
fety
in p
regn
ant
wo
men
P
op
ula
tio
n: P
regn
ant w
omen
In
terv
enti
on
: 1-2
dos
es o
f the
cur
rent
ly a
vaila
ble
kille
d, w
hole
-cel
l ora
l cho
lera
vac
cine
s (O
CVs)
C
om
par
iso
n: P
lace
bo o
r no
vacc
ine/
oth
er p
reve
ntio
n an
d co
ntro
l mea
sure
s (e.
g. W
ASH)
O
utc
om
e: P
regn
ancy
-spe
cific
mat
erna
l/fet
al/n
eona
tal s
erio
us a
dver
se e
vent
s fol
low
ing
imm
uniza
tion
Wha
t is t
he e
vide
nce
that
the
curr
ently
ava
ilabl
e ki
lled,
who
le c
ell O
CVs a
re sa
fe in
pre
gnan
cy?
Ra
ting
Adju
stm
ent t
o Ra
ting
Qua
lity
of
Evid
ence
No.
of s
tudi
es/s
tart
ing
ratin
g 1
RCT/
3
Obs
erva
tiona
l 4
Fact
ors
decr
easin
g co
nfid
ence
Lim
itatio
n in
stud
y de
sign
Serio
us1
-2
In
cons
isten
cy
No
serio
us
0 In
dire
ctne
ss
No
serio
us
0 Im
prec
ision
N
o se
rious
0
Publ
icat
ion
Bias
N
o se
rious
0
Fact
ors
Incr
easin
g Co
nfid
ence
Larg
e ef
fect
N
ot a
pplic
able
0
Dose
-res
pons
e N
ot a
pplic
able
0
Anta
goni
stic
bia
s and
co
nfou
ndin
g N
ot a
pplic
able
0
Fina
l num
eric
al ra
ting
of q
ualit
y of
evi
denc
e 2
Sum
mar
y of
Fin
ding
s
Stat
emen
t on
qual
ity o
f evi
denc
e
Evid
ence
supp
orts
a
limite
d le
vel o
f co
nfid
ence
that
the
true
effe
ct li
es c
lose
to
that
of t
he e
stim
ate
of
the
effe
ct o
n th
e he
alth
ou
tcom
e.
Conc
lusio
n
Low
leve
l of s
cien
tific
ev
iden
ce th
at th
e cu
rren
tly li
cens
ed O
CVs
are
safe
for u
se d
urin
g pr
egna
ncy.
1 K
ahn
et a
l., th
e st
udy
was
nes
ted
in a
RCT
, but
not
pow
ered
to d
etec
t a p
rede
fined
a p
riori
risk
(no
spec
ific
sam
ple
size
calc
ulat
ion)
. The
con
trol
gro
up c
ompr
ised
preg
nant
wom
en e
xclu
ded
from
the
tria
l in
the
base
line
asse
ssm
ent
for b
eing
pre
gnan
t (i.e
. non
-ran
dom
ized
wom
en).
Vacc
inat
ed a
nd n
on-v
acci
nate
d pr
egna
nt w
omen
diff
ered
in th
e ba
selin
e ris
k fo
r adv
erse
pre
gnan
cy o
utco
mes
. The
sam
ple
size
was
smal
l (69
exp
osed
and
69
non-
expo
sed
wom
en
incl
uded
in th
e an
alys
is). T
he a
sses
smen
t of t
he p
regn
ancy
out
com
es w
as d
one
retr
ospe
ctiv
ely
and
the
prim
ary
outc
ome
was
any
adv
erse
eve
nt (n
o ad
just
ed e
stim
ates
pro
vide
d fo
r spe
cific
adv
erse
pre
gnan
cy o
utco
mes
).
Page
10
of 2
9
Re
fere
nce
s
1.
Gr
out L
et a
l. Pr
egna
ncy
Out
com
es a
fter
a M
ass V
acci
natio
n Ca
mpa
ign
with
an
Ora
l Cho
lera
Va
ccin
e in
Gui
nea:
A R
etro
spec
tive
Coho
rt. P
LoS
Negl
Tro
p Di
s 201
5. 9
(12)
: e00
0427
4 2.
Ha
shim
R e
t al.
Safe
ty o
f the
reco
mbi
nant
cho
lera
toxi
n B
subu
nit,
kille
d w
hole
-cel
l (rB
S-W
C) o
ral
chol
era
vacc
ine
in p
regn
ancy
. PLo
S Ne
gl T
rop
Dis 2
012;
6(7
): e1
743.
3.
Al
i M e
t al.
Safe
ty o
f a k
illed
ora
l cho
lera
vac
cine
(Sha
ncho
l) in
pre
gnan
t wom
en in
Mal
awi:
an
obse
rvat
iona
l coh
ort s
tudy
. Lan
cet I
nfec
t Dis
2017
. 4.
Kh
an A
I et a
l. Sa
fety
of t
he o
ral c
hole
ra v
acci
ne in
pre
gnan
cy: R
etro
spec
tive
findi
ngs f
rom
a
subg
roup
follo
win
g m
ass v
acci
natio
n ca
mpa
ign
in D
haka
, Ban
glad
esh.
Vac
cine
201
7.
Page
11
of 2
9
Effi
cacy
an
d E
ffec
tive
ne
ss
Po
pu
lati
on
: Non
-pre
gnan
t adu
lts a
nd c
hild
ren
≥ 1
year
old
(Sha
ncho
l/Euv
icho
l/mO
RCVa
x) o
r ≥ 2
yea
rs o
ld
(Duk
oral
) In
terv
enti
on
: 2 d
oses
of t
he c
urre
ntly
ava
ilabl
e ki
lled,
who
le-c
ell o
ral c
hole
ra v
acci
nes (
OCV
s)
Co
mp
aris
on
: Pla
cebo
or n
o va
ccin
e/ o
ther
pre
vent
ion
and
cont
rol m
easu
res (
e.g.
WAS
H)
Ou
tco
me:
Cas
es o
f cho
lera
W
hat i
s the
evi
denc
e fo
r pro
tect
ive
effic
acy
and
effe
ctiv
enes
s aga
inst
cho
lera
(any
seve
rity)
of t
he
curr
ently
ava
ilabl
e ki
lled,
who
le c
ell O
CVs f
ollo
win
g im
mun
izat
ion
amon
g in
divi
dual
s ≥ 1
yea
r old
?
Ratin
g Ad
just
men
t to
Ratin
g
Qua
lity
of
Evid
ence
No.
of s
tudi
es/s
tart
ing
ratin
g 11
RCT
/ 7
obse
rvat
iona
l 4
Fact
ors
decr
easin
g co
nfid
ence
Lim
itatio
n in
stud
y de
sign
No
serio
us
0 In
cons
isten
cy
No
serio
us
0 In
dire
ctne
ss
No
serio
us
0 Im
prec
ision
N
o se
rious
0
Publ
icat
ion
Bias
N
o se
rious
0
Fact
ors
Incr
easin
g Co
nfid
ence
Larg
e ef
fect
N
ot a
pplic
able
0
Dose
-res
pons
e N
ot a
pplic
able
0
Anta
goni
stic
bia
s and
co
nfou
ndin
g N
ot a
pplic
able
0
Fina
l num
eric
al ra
ting
of q
ualit
y of
evi
denc
e 4
Sum
mar
y of
Fin
ding
s
Stat
emen
t on
qual
ity o
f evi
denc
e
Evid
ence
supp
orts
a
high
leve
l of c
onfid
ence
th
at th
e tr
ue e
ffect
lies
cl
ose
to th
at o
f the
he
alth
out
com
e.
Conc
lusio
n
High
leve
l of s
cien
tific
ev
iden
ce th
at th
e cu
rren
tly li
cens
ed o
ral
chol
era
vacc
ines
are
ef
ficac
ious
and
ef
fect
ive
agai
nst
chol
era.
R
efe
ren
ces:
1.
Clem
ens J
D et
al.
Fiel
d tr
ial o
f ora
l cho
lera
vac
cine
s in
Bang
lade
sh: r
esul
ts fr
om th
ree-
year
follo
w-
up e
t al.
Lanc
et 1
990;
335
(868
4): 2
70-2
73.
2.
Sanc
hez J
L et
al.
Prot
ectiv
e ef
ficac
y of
ora
l who
le-c
ell/r
ecom
bina
nt-B
-sub
unit
chol
era
vacc
ine
in
Peru
vian
mili
tary
recr
uits
. Lan
cet 1
994;
344
(893
2): 1
273-
1276
.
Page
12
of 2
9
3.
Tayl
or D
N e
t al.
Two-
year
stud
y of
the
prot
ectiv
e ef
ficac
y of
the
oral
who
le c
ell p
lus r
ecom
bina
nt B
su
buni
t cho
lera
vac
cine
in P
eru.
JID
2000
; 181
(5):
1667
-167
3.
4.
Trac
h DD
et a
l. Fi
eld
tria
l of a
loca
lly p
rodu
ced,
kill
ed, o
ral c
hole
ra v
acci
ne in
Vie
tnam
. Lan
cet 1
997;
34
9(90
47):
231-
235.
5.
Su
r D e
t al.
Effic
acy
and
safe
ty o
f a m
odifi
ed k
illed
-who
le-c
ell o
ral c
hole
ra v
acci
ne in
Indi
a: a
n in
terim
ana
lysis
of a
clu
ster
-ran
dom
ised,
dou
ble-
blin
d, p
lace
bo-c
ontr
olle
d tr
ial.
Lanc
et 2
009;
374
: 16
94-1
702.
6.
Bh
atta
char
ya S
K, e
t al.
5 ye
ar e
ffica
cy o
f a b
ival
ent k
illed
who
le-c
ell o
ral c
hole
ra v
acci
ne in
Kol
kata
, In
dia:
a c
lust
er-r
ando
mise
d, d
oubl
e-bl
ind,
pla
cebo
-con
trol
led
tria
l. La
ncet
201
3; 1
3(12
); 10
50-1
056.
7.
De
sai S
N e
t al.
A Ra
ndom
ized,
Pla
cebo
-Con
trol
led
Tria
l Eva
luat
ing
Safe
ty a
nd Im
mun
ogen
icity
of
the
Kille
d, B
ival
ent,
Who
le-C
ell O
ral C
hole
ra V
acci
ne in
Eth
iopi
a. A
m J
Trop
Med
Hyg
201
5; 9
3(3)
: 52
7-53
3.
8.
Qad
ri, F
et a
l. Ef
ficac
y of
a S
ingl
e-Do
se, I
nact
ivat
ed O
ral C
hole
ra V
acci
ne in
Ban
glad
esh.
NEJ
M 2
016;
37
4: 1
723-
1732
.
9.
Baik
YO
et a
l. A
rand
omize
d, n
on-in
ferio
rity
tria
l com
parin
g tw
o bi
vale
nt k
illed
, who
le c
ell,
oral
ch
oler
a va
ccin
es (E
uvic
hol v
s Sha
ncho
l) in
the
Phili
ppin
es. V
acci
ne 2
015;
33(
46):
6360
-636
5.
10. Q
adri
F et
al.
Feas
ibili
ty a
nd e
ffect
iven
ess o
f ora
l cho
lera
vac
cine
in a
n ur
ban
ende
mic
sett
ing
in
Bang
lade
sh: a
clu
ster
rand
omise
d op
en-la
bel t
rial.
Lanc
et 2
015;
386
:136
2-13
71.
11. v
an L
oon
FPL
et a
l. Fi
eld
tria
l of i
nact
ivat
ed o
ral c
hole
ra v
acci
nes i
n Ba
ngla
desh
: res
ults
from
5 y
ears
of
follo
w-u
p. V
acci
ne 1
996;
14(
2): 1
62-1
66.
12. L
ucas
MES
et a
l. Ef
fect
iven
ess o
f Mas
s Ora
l Cho
lera
Vac
cina
tion
in B
eira
, Moz
ambi
que.
NEJ
M 2
005;
35
2: 7
57-7
67.
13
. Kha
tib A
M e
t al.
Effe
ctiv
enes
s of a
n or
al c
hole
ra v
acci
ne in
Zan
zibar
: fin
ding
s fro
m a
mas
s va
ccin
atio
n ca
mpa
ign
and
obse
rvat
iona
l coh
ort s
tudy
. Lan
cet I
nf D
is 20
12; 1
2(11
): 83
7-84
4.
14. W
ierz
ba T
F et
al.
Effe
ctiv
enes
s of a
n or
al c
hole
ra v
acci
ne c
ampa
ign
to p
reve
nt c
linic
ally
-sig
nific
ant
chol
era
in O
dish
a St
ate,
Indi
a. V
acci
ne 2
015;
33(
21):
2463
-246
9.
15. Iv
ers L
C et
al.
Effe
ctiv
enes
s of r
eact
ive
oral
cho
lera
vac
cina
tion
in ru
ral H
aiti:
a c
ase-
cont
rol s
tudy
an
d bi
as-in
dica
tor a
naly
sis. L
ance
t Glo
bal H
ealth
201
5; 3
(3):
162-
168.
16
. Sev
ere
K et
al.
Effe
ctiv
enes
s of O
ral C
hole
ra V
acci
ne in
Hai
ti: 3
7-M
onth
Fol
low
-Up.
Am
J Tr
op M
ed
Hyg
2016
; 94(
5): 1
136-
1942
. 17
. Luq
uero
FJ e
t al.
Use
of V
ibrio
cho
lera
e va
ccin
e in
an
outb
reak
in G
uine
a. N
ew E
ngla
nd Jo
urna
l of
Med
icin
e 20
14; 3
70(2
2): 2
111-
20.
18. T
hiem
VD
et a
l. Lo
ng-t
erm
effe
ctiv
enes
s aga
inst
cho
lera
of o
ral k
illed
who
le-c
ell v
acci
ne p
rodu
ced
in V
ietn
am. V
acci
ne 2
006;
24(
20):
4297
-430
3.
Page
13
of 2
9
Effi
cacy
an
d E
ffec
tive
nes
s, s
ever
e ch
ole
ra
Po
pu
lati
on
: Non
-pre
gnan
t adu
lts a
nd c
hild
ren
≥ 1
year
old
(Sha
ncho
l/Euv
icho
l/mO
RCVa
x) o
r ≥ 2
yea
rs o
ld
(Duk
oral
) In
terv
enti
on
: 2 d
oses
of t
he c
urre
ntly
ava
ilabl
e ki
lled,
who
le-c
ell o
ral c
hole
ra v
acci
nes (
OCV
s)
Co
mp
aris
on
: Pla
cebo
or n
o va
ccin
e/ot
her p
reve
ntio
n an
d co
ntro
l mea
sure
s (e.
g. W
ASH)
O
utc
om
e: C
ases
of s
ever
e ch
oler
a
Wha
t is t
he e
vide
nce
for p
rote
ctiv
e ef
ficac
y an
d ef
fect
iven
ess a
gain
st se
vere
cho
lera
of t
he c
urre
ntly
av
aila
ble
kille
d, w
hole
cell
OCV
s am
ong
indi
vidu
als ≥
1 y
ear o
ld?
Ra
ting
Adju
stm
ent t
o Ra
ting
Qua
lity
of
Evid
ence
No.
of s
tudi
es/s
tart
ing
ratin
g 5
RCT/
1 ob
serv
atio
nal
4
Fact
ors
decr
easin
g co
nfid
ence
Lim
itatio
n in
stud
y de
sign
No
serio
us
0 In
cons
isten
cy
No
serio
us
0 In
dire
ctne
ss
No
serio
us
0 Im
prec
ision
N
o se
rious
0
Publ
icat
ion
Bias
N
o se
rious
0
Fact
ors
Incr
easin
g Co
nfid
ence
Larg
e ef
fect
N
ot a
pplic
able
0
Dose
-res
pons
e N
ot a
pplic
able
0
Anta
goni
stic
bia
s and
co
nfou
ndin
g N
ot a
pplic
able
0
Fina
l num
eric
al ra
ting
of q
ualit
y of
evi
denc
e 4
Sum
mar
y of
Fin
ding
s
Stat
emen
t on
qual
ity o
f evi
denc
e
Evid
ence
supp
orts
a
high
leve
l of c
onfid
ence
th
at th
e tr
ue e
ffect
lies
cl
ose
to th
e ef
fect
on
the
heal
th o
utco
me.
Conc
lusio
n
High
leve
l of s
cien
tific
ev
iden
ce th
at th
e cu
rren
tly li
cens
ed o
ral
chol
era
vacc
ines
are
ef
ficac
ious
and
ef
fect
ive
in p
rote
ctin
g ag
ains
t sev
ere
chol
era.
R
efe
ren
ces:
1.
Clem
ens J
D et
al.
Fiel
d tr
ial o
f ora
l cho
lera
vac
cine
s in
Bang
lade
sh: r
esul
ts fr
om th
ree-
year
follo
w-
up. L
ance
t 199
0; 3
35(8
684)
: 270
-273
. 2.
Ta
ylor
DN
et a
l. Tw
o-ye
ar st
udy
of th
e pr
otec
tive
effic
acy
of th
e or
al w
hole
cel
l plu
s rec
ombi
nant
B
subu
nit c
hole
ra v
acci
ne in
Per
u. JI
D 20
00; 1
81(5
): 16
67-1
673.
Page
14
of 2
9
3.
Trac
h DD
et a
l. Fi
eld
tria
l of a
loca
lly p
rodu
ced,
kill
ed, o
ral c
hole
ra v
acci
ne in
Vie
tnam
. Lan
cet
1997
; 349
(904
7): 2
31-2
35.
4.
Qad
ri F
et a
l. Ef
ficac
y of
a S
ingl
e-Do
se, I
nact
ivat
ed O
ral C
hole
ra V
acci
ne in
Ban
glad
esh.
NEJ
M
2016
; 374
: 172
3-17
32.
5.
Q
adri
F et
al.
Feas
ibili
ty a
nd e
ffect
iven
ess o
f ora
l cho
lera
vac
cine
in a
n ur
ban
ende
mic
sett
ing
in
Bang
lade
sh: a
clu
ster
rand
omise
d op
en-la
bel t
rial.
Lanc
et 2
015;
386
:136
2-13
71.
6.
Luca
s MES
et a
l. Ef
fect
iven
ess o
f Mas
s Ora
l Cho
lera
Vac
cina
tion
in B
eira
, Moz
ambi
que.
NEJ
M
2005
; 352
: 757
-767
.
Page
15
of 2
9
Effi
cacy
an
d E
ffec
tive
nes
s, <
5 ye
ars
old
, an
y ch
ole
ra
Po
pu
lati
on
: Chi
ldre
n <5
yea
rs o
f age
In
terv
enti
on
: 2 d
oses
of t
he c
urre
ntly
ava
ilabl
e ki
lled,
who
le-c
ell o
ral c
hole
ra v
acci
nes (
OCV
s)
Co
mp
aris
on
: Pla
cebo
or n
o va
ccin
e/ o
ther
pre
vent
ion
and
cont
rol m
easu
res (
e.g.
WAS
H)
Ou
tco
me:
Cas
es o
f cho
lera
(any
seve
rity)
W
hat i
s the
evi
denc
e fo
r pro
tect
ive
effic
acy
and
effe
ctiv
enes
s aga
inst
cho
lera
(any
seve
rity)
of t
he
curr
ently
ava
ilabl
e ki
lled,
who
le c
ell O
CVs a
mon
g in
divi
dual
s <5
year
s of a
ge?
Ra
ting
Adju
stm
ent t
o Ra
ting
Qua
lity
of
Evid
ence
No.
of s
tudi
es/s
tart
ing
ratin
g 9
RCT/
2 ob
serv
atio
nal
4
Fact
ors
decr
easin
g co
nfid
ence
Lim
itatio
n in
stud
y de
sign
No
serio
us
0 In
cons
isten
cy
No
serio
us
0 In
dire
ctne
ss
No
serio
us
0 Im
prec
ision
1 Se
rious
-1
Pu
blic
atio
n Bi
as
No
serio
us
0
Fact
ors
Incr
easin
g Co
nfid
ence
Larg
e ef
fect
N
ot a
pplic
able
0
Dose
-res
pons
e N
ot a
pplic
able
0
Anta
goni
stic
bia
s and
co
nfou
ndin
g N
ot a
pplic
able
0
Fina
l num
eric
al ra
ting
of q
ualit
y of
evi
denc
e 3
Sum
mar
y of
Fin
ding
s
Stat
emen
t on
qual
ity o
f evi
denc
e
Evid
ence
supp
orts
a
mod
erat
e le
vel o
f co
nfid
ence
that
the
true
ef
fect
lies
clo
se to
the
effe
ct o
f tha
t of t
he
estim
ate
of th
e ef
fect
on
the
heal
th o
utco
me.
Conc
lusio
n
Mod
erat
e le
vel o
f sc
ient
ific
evid
ence
that
the
curr
ently
lice
nsed
ora
l ch
oler
a va
ccin
es a
re
effic
acio
us a
nd e
ffect
ive
agai
nst c
hole
ra (a
ny
seve
rity)
. 1 M
ost o
f the
clin
ical
tria
ls w
ere
not p
ower
ed to
car
ryou
t sub
-gro
up a
naly
sis re
sulti
ng in
impr
ecise
poi
nt e
stim
ates
in
chi
ldre
n un
der-
five.
Page
16
of 2
9
Re
fere
nce
s:
1.
Cl
emen
s JD
et a
l. Fi
eld
tria
l of o
ral c
hole
ra v
acci
nes i
n Ba
ngla
desh
: res
ults
from
thre
e-ye
ar fo
llow
-up
et a
l. La
ncet
199
0; 3
35(8
684)
: 270
-273
. 2.
Ta
ylor
DN
et a
l. Tw
o-ye
ar st
udy
of th
e pr
otec
tive
effic
acy
of th
e or
al w
hole
cel
l plu
s rec
ombi
nant
B
subu
nit c
hole
ra v
acci
ne in
Per
u. JI
D 20
00; 1
81(5
): 16
67-1
673.
3.
Tr
ach
DD e
t al.
Fiel
d tr
ial o
f a lo
cally
pro
duce
d, k
illed
, ora
l cho
lera
vac
cine
in V
ietn
am. L
ance
t 199
7;
349(
9047
): 23
1-23
5.
4.
Sur D
et a
l. Ef
ficac
y an
d sa
fety
of a
mod
ified
kill
ed-w
hole
-cel
l ora
l cho
lera
vac
cine
in In
dia:
an
inte
rim a
naly
sis o
f a c
lust
er-r
ando
mise
d, d
oubl
e-bl
ind,
pla
cebo
-con
trol
led
tria
l. La
ncet
200
9; 3
74:
1694
-170
2.
5.
Bhat
tach
arya
SK
et a
l. 5
year
effi
cacy
of a
biv
alen
t kill
ed w
hole
-cel
l ora
l cho
lera
vac
cine
in K
olka
ta,
Indi
a: a
clu
ster
-ran
dom
ised,
dou
ble-
blin
d, p
lace
bo-c
ontr
olle
d tr
ial.
Lanc
et 2
013;
13(
12);
1050
-105
6.
6.
Saha
A e
t al.
Safe
ty a
nd im
mun
ogen
icity
stud
y of
a k
illed
biv
alen
t (O
1 an
d O
139)
who
le-c
ell o
ral
chol
era
vacc
ine
Shan
chol
, in
Bang
lade
shi a
dults
and
chi
ldre
n as
you
ng a
s 1 y
ear o
f age
. Vac
cine
20
11; 2
9(46
): 82
85-8
295.
7.
De
sai S
N e
t al.
A Ra
ndom
ized,
Pla
cebo
-Con
trol
led
Tria
l Eva
luat
ing
Safe
ty a
nd Im
mun
ogen
icity
of t
he
Kille
d, B
ival
ent,
Who
le-C
ell O
ral C
hole
ra V
acci
ne in
Eth
iopi
a. A
m J
Trop
Med
Hyg
201
5; 9
3(3)
: 527
-53
3.
8.
Qad
ri, F
et a
l. Ef
ficac
y of
a S
ingl
e-Do
se, I
nact
ivat
ed O
ral C
hole
ra V
acci
ne in
Ban
glad
esh.
NEJ
M 2
016;
37
4: 1
723-
1732
.
9.
Bhat
tach
arya
SK
et a
l. 5
year
effi
cacy
of a
biv
alen
t kill
ed w
hole
-cel
l ora
l cho
lera
vac
cine
in K
olka
ta,
Indi
a: a
clu
ster
-ran
dom
ised,
dou
ble-
blin
d, p
lace
bo-c
ontr
olle
d tr
ial.
Lanc
et 2
013;
13(
12);
1050
-105
6.
10. L
ucas
MES
et a
l. Ef
fect
iven
ess o
f Mas
s Ora
l Cho
lera
Vac
cina
tion
in B
eira
, Moz
ambi
que.
NEJ
M 2
005;
35
2: 7
57-7
67.
11
. Iver
s LC
et a
l. Ef
fect
iven
ess o
f rea
ctiv
e or
al c
hole
ra v
acci
natio
n in
rura
l Hai
ti: a
cas
e-co
ntro
l stu
dy
and
bias
-indi
cato
r ana
lysis
. Lan
cet G
loba
l Hea
lth 2
015;
3(3
): 16
2-16
8.
Page
17
of 2
9
Effi
cacy
an
d E
ffec
tive
nes
s, <
5 ye
ars
old
, sev
ere
cho
lera
P
op
ula
tio
n: C
hild
ren
<5 y
ears
of a
ge
Inte
rven
tio
n: 2
dos
es o
f the
cur
rent
ly a
vaila
ble
kille
d, w
hole
-cel
l ora
l cho
lera
vac
cine
s (O
CVs)
C
om
par
iso
n: P
lace
bo o
r no
vacc
ine/
othe
r pre
vent
ion
and
cont
rol m
easu
res (
e.g.
WAS
H)
Ou
tco
me:
Cas
es o
f sev
ere
chol
era
W
hat i
s the
evi
denc
e fo
r pro
tect
ive
effic
acy
and
effe
ctiv
enes
s aga
inst
seve
re c
hole
ra o
f the
cur
rent
ly
avai
labl
e ki
lled,
who
le ce
ll O
CVs a
mon
g in
divi
dual
s <5
yea
rs o
f age
?
Ratin
g Ad
just
men
t to
Ratin
g
Qua
lity
of
Evid
ence
No.
of s
tudi
es/s
tart
ing
ratin
g 2
RCT
4
Fact
ors
decr
easin
g co
nfid
ence
Lim
itatio
n in
stud
y de
sign
No
serio
us
0 In
cons
isten
cy
No
serio
us
0 In
dire
ctne
ss
No
serio
us
0 Im
prec
ision
1 N
o se
rious
-1
Pu
blic
atio
n Bi
as
No
serio
us
0
Fact
ors
Incr
easin
g Co
nfid
ence
Larg
e ef
fect
N
ot a
pplic
able
0
Dose
-res
pons
e N
ot a
pplic
able
0
Anta
goni
stic
bia
s and
co
nfou
ndin
g N
ot a
pplic
able
0
Fina
l num
eric
al ra
ting
of q
ualit
y of
evi
denc
e 3
Sum
mar
y of
Fin
ding
s
Stat
emen
t on
qual
ity o
f evi
denc
e
Evid
ence
supp
orts
a
mod
erat
e le
vel o
f co
nfid
ence
that
the
true
ef
fect
lies
clo
se to
that
of
the
estim
ate
of th
e ef
fect
on
the
heal
th o
utco
me.
Conc
lusio
n
Mod
erat
e le
vel o
f sci
entif
ic
evid
ence
that
the
curr
ently
lic
ense
d or
al c
hole
ra
vacc
ines
are
effi
caci
ous
and
effe
ctiv
e ag
ains
t se
vere
cho
lera
in c
hild
ren
unde
r 5.
1 Mos
t of t
he c
linic
al tr
ials
wer
e no
t pow
ered
to c
arry
out s
ub-g
roup
ana
lysis
resu
lting
in im
prec
ise p
oint
est
imat
es in
ch
ildre
n un
der-
five.
Re
fere
nce
s:
1.
Qad
ri F
et a
l. Ef
ficac
y of
a S
ingl
e-Do
se, I
nact
ivat
ed O
ral C
hole
ra V
acci
ne in
Ban
glad
esh.
NEJ
M 2
016;
37
4: 1
723-
1732
.
2.
Qad
ri F
et a
l. Fe
asib
ility
and
effe
ctiv
enes
s of o
ral c
hole
ra v
acci
ne in
an
urba
n en
dem
ic se
ttin
g in
Ba
ngla
desh
: a c
lust
er ra
ndom
ised
open
-labe
l tria
l. La
ncet
201
5; 3
86:1
362-
1371
.
Page
18
of 2
9
Effi
cacy
an
d E
ffec
tive
nes
s, 5
-14
year
s o
ld, a
ny
cho
lera
P
op
ula
tio
n: C
hild
ren
and
adol
esce
nts 5
-14
year
s of a
ge
Inte
rven
tio
n: 2
dos
es o
f the
cur
rent
ly a
vaila
ble
kille
d, w
hole
-cel
l ora
l cho
lera
vac
cine
s (O
CVs)
C
om
par
iso
n: P
lace
bo o
r no
vacc
ine/
othe
r pre
vent
ion
and
cont
rol m
easu
res (
e.g.
WAS
H)
Ou
tco
me:
Cas
es o
f cho
lera
(any
seve
rity)
W
hat i
s the
evi
denc
e fo
r pro
tect
ive
effic
acy
and
effe
ctiv
enes
s aga
inst
cho
lera
(any
seve
rity)
of t
he
curr
ently
ava
ilabl
e ki
lled,
who
le c
ell O
CVs a
mon
g in
divi
dual
s 5-1
4 ye
ars o
f age
old
?
Ratin
g Ad
just
men
t to
Ratin
g
Qua
lity
of
Evid
ence
No.
of s
tudi
es/s
tart
ing
ratin
g 7
RCT
4
Fact
ors
decr
easin
g co
nfid
ence
Lim
itatio
n in
stud
y de
sign
No
serio
us
0 In
cons
isten
cy
No
serio
us
0 In
dire
ctne
ss
No
serio
us
0 Im
prec
ision
N
o se
rious
0
Publ
icat
ion
Bias
N
o se
rious
0
Fact
ors
Incr
easin
g Co
nfid
ence
Larg
e ef
fect
N
ot a
pplic
able
0
Dose
-res
pons
e N
ot a
pplic
able
0
Anta
goni
stic
bia
s and
co
nfou
ndin
g N
ot a
pplic
able
0
Fina
l num
eric
al ra
ting
of q
ualit
y of
evi
denc
e 4
Sum
mar
y of
Fin
ding
s
Stat
emen
t on
qual
ity o
f evi
denc
e
Evid
ence
supp
orts
a
high
leve
l of c
onfid
ence
th
at th
e tr
ue e
ffect
lies
cl
ose
to th
at o
f the
es
timat
e on
the
effe
ct
of th
e he
alth
out
com
e.
Conc
lusio
n
High
leve
l of s
cien
tific
ev
iden
ce th
at th
e cu
rren
tly li
cens
ed o
ral
chol
era
vacc
ines
are
ef
ficac
ious
and
effe
ctiv
e ag
ains
t cho
lera
of a
ny
seve
rity
in in
divi
dual
s 5-
14 y
ears
of a
ge.
Page
19
of 2
9
Re
fere
nce
s:
1.
Ta
ylor
DN
et a
l. Tw
o-ye
ar st
udy
of th
e pr
otec
tive
effic
acy
of th
e or
al w
hole
cel
l plu
s rec
ombi
nant
B
subu
nit c
hole
ra v
acci
ne in
Per
u. JI
D 20
00; 1
81(5
): 16
67-1
673.
2.
Su
r D e
t al.
Effic
acy
and
safe
ty o
f a m
odifi
ed k
illed
-who
le-c
ell o
ral c
hole
ra v
acci
ne in
Indi
a: a
n in
terim
an
alys
is of
a c
lust
er-r
ando
mise
d, d
oubl
e-bl
ind,
pla
cebo
-con
trol
led
tria
l. La
ncet
200
9; 3
74: 1
694-
1702
. 3.
Bh
atta
char
ya S
K et
al.
5 ye
ar e
ffica
cy o
f a b
ival
ent k
illed
who
le-c
ell o
ral c
hole
ra v
acci
ne in
Kol
kata
, In
dia:
a c
lust
er-r
ando
mise
d, d
oubl
e-bl
ind,
pla
cebo
-con
trol
led
tria
l. La
ncet
201
3; 1
3(12
); 10
50-1
056.
4.
Sa
ha A
et a
l. Sa
fety
and
imm
unog
enic
ity st
udy
of a
kill
ed b
ival
ent (
O1
and
O13
9) w
hole
-cel
l ora
l ch
oler
a va
ccin
e Sh
anch
ol, i
n Ba
ngla
desh
i adu
lts a
nd c
hild
ren
as y
oung
as 1
yea
r of a
ge. V
acci
ne 2
011;
29
(46)
: 828
5-82
95.
5.
Desa
i SN
et a
l. A
Rand
omize
d, P
lace
bo-C
ontr
olle
d Tr
ial E
valu
atin
g Sa
fety
and
Imm
unog
enic
ity o
f the
Ki
lled,
Biv
alen
t, W
hole
-Cel
l Ora
l Cho
lera
Vac
cine
in E
thio
pia.
Am
J Tr
op M
ed H
yg 2
015;
93(
3): 5
27-
533.
6.
Q
adri
F et
al.
Effic
acy
of a
Sin
gle-
Dose
, Ina
ctiv
ated
Ora
l Cho
lera
Vac
cine
in B
angl
ades
h. N
EJM
201
6;
374:
172
3-17
32.
7.
Bh
atta
char
ya S
K et
al.
5 ye
ar e
ffica
cy o
f a b
ival
ent k
illed
who
le-c
ell o
ral c
hole
ra v
acci
ne in
Kol
kata
, In
dia:
a c
lust
er-r
ando
mise
d, d
oubl
e-bl
ind,
pla
cebo
-con
trol
led
tria
l. La
ncet
201
3; 1
3(12
); 10
50-1
056.
Page
20
of 2
9
Effi
cacy
an
d E
ffec
tive
nes
s, 5
-14
year
s o
ld, s
ever
e ch
ole
ra
Po
pu
lati
on
: Chi
ldre
n an
d ad
oles
cent
s 5-1
4 ye
ars o
f age
In
terv
enti
on
: 2 d
oses
of t
he c
urre
ntly
ava
ilabl
e ki
lled,
who
le-c
ell o
ral c
hole
ra v
acci
nes (
OCV
s)
Co
mp
aris
on
: Pla
cebo
or n
o va
ccin
e/ot
her p
reve
ntio
n an
d co
ntro
l mea
sure
s (e.
g. W
ASH)
O
utc
om
e: C
ases
of s
ever
e ch
oler
a
Wha
t is t
he e
vide
nce
for p
rote
ctiv
e ef
ficac
y an
d ef
fect
iven
ess a
gain
st se
vere
cho
lera
of t
he c
urre
ntly
av
aila
ble
kille
d, w
hole
cell
OCV
s am
ong
indi
vidu
als 5
-14
year
s of a
ge?
Ra
ting
Adju
stm
ent t
o Ra
ting
Qua
lity
of
Evid
ence
No.
of s
tudi
es/s
tart
ing
ratin
g 2
RCT
4
Fact
ors
decr
easin
g co
nfid
ence
Lim
itatio
n in
stud
y de
sign
No
serio
us
0 In
cons
isten
cy
No
serio
us
0 In
dire
ctne
ss
No
serio
us
0 Im
prec
ision
N
o se
rious
0
Publ
icat
ion
Bias
N
o se
rious
0
Fact
ors
Incr
easin
g Co
nfid
ence
Larg
e ef
fect
N
ot a
pplic
able
0
Dose
-res
pons
e N
ot a
pplic
able
0
Anta
goni
stic
bia
s and
co
nfou
ndin
g N
ot a
pplic
able
0
Fina
l num
eric
al ra
ting
of q
ualit
y of
evi
denc
e 4
Sum
mar
y of
Fin
ding
s
Stat
emen
t on
qual
ity o
f evi
denc
e
Evid
ence
supp
orts
a
high
leve
l of c
onfid
ence
th
at th
e tr
ue e
ffect
lies
cl
ose
to th
e es
timat
e of
th
e ef
fect
on
the
heal
th
outc
ome.
Conc
lusio
n
High
leve
l of s
cien
tific
ev
iden
ce th
at th
e cu
rren
tly li
cens
ed o
ral
chol
era
vacc
ines
are
ef
ficac
ious
and
effe
ctiv
e in
chi
ldre
n an
d ad
oles
cent
s 5-1
4 ye
ars
agai
nst s
ever
e ch
oler
a.
Re
fere
nce
s:
1.
Q
adri
F et
al.
Effic
acy
of a
Sin
gle-
Dose
, Ina
ctiv
ated
Ora
l Cho
lera
Vac
cine
in B
angl
ades
h. N
EJM
201
6;
374:
172
3-17
32.
2.
Q
adri
F et
al.
Feas
ibili
ty a
nd e
ffect
iven
ess o
f ora
l cho
lera
vac
cine
in a
n ur
ban
ende
mic
sett
ing
in
Bang
lade
sh: a
clu
ster
rand
omise
d op
en-la
bel t
rial.
Lanc
et 2
015;
386
:136
2-13
71.
Page
21
of 2
9
Effi
cacy
an
d E
ffec
tive
nes
s, >
14 y
ears
old
, an
y ch
ole
ra
Po
pu
lati
on
: Ado
lesc
ents
and
adu
lts >
14 y
ears
of a
ge
Inte
rven
tio
n: 2
dos
es o
f the
cur
rent
ly a
vaila
ble
kille
d, w
hole
-cel
l ora
l cho
lera
vac
cine
s (O
CVs)
C
om
par
iso
n: P
lace
bo o
r no
vacc
ine/
othe
r pre
vent
ion
and
cont
rol m
easu
res (
e.g.
WAS
H)
Ou
tco
me:
Cas
es o
f cho
lera
W
hat i
s the
evi
denc
e fo
r pro
tect
ive
effic
acy
and
effe
ctiv
enes
s aga
inst
cho
lera
(any
seve
rity)
of t
he
curr
ently
ava
ilabl
e ki
lled,
who
le c
ell O
CVs a
mon
g in
divi
dual
s ≥ 1
4 ye
ars o
f age
?
Ratin
g Ad
just
men
t to
Ratin
g
Qua
lity
of
Evid
ence
No.
of s
tudi
es/s
tart
ing
ratin
g 9
RCT/
2 O
bser
vatio
nal
4
Fact
ors
decr
easin
g co
nfid
ence
Lim
itatio
n in
stud
y de
sign
No
serio
us
0 In
cons
isten
cy
No
serio
us
0 In
dire
ctne
ss
No
serio
us
0 Im
prec
ision
N
o se
rious
0
Publ
icat
ion
Bias
N
o se
rious
0
Fact
ors
Incr
easin
g Co
nfid
ence
Larg
e ef
fect
N
ot a
pplic
able
0
Dose
-res
pons
e N
ot a
pplic
able
0
Anta
goni
stic
bia
s and
co
nfou
ndin
g N
ot a
pplic
able
0
Fina
l num
eric
al ra
ting
of q
ualit
y of
evi
denc
e 4
Sum
mar
y of
Fin
ding
s
Stat
emen
t on
qual
ity o
f evi
denc
e
Evid
ence
supp
orts
a
high
leve
l of c
onfid
ence
th
at th
e tr
ue e
ffect
lies
cl
ose
to th
e es
timat
e of
th
e ef
fect
on
the
heal
th
outc
ome.
Conc
lusio
n
High
leve
l of s
cien
tific
ev
iden
ce th
at th
e cu
rren
tly li
cens
ed o
ral
chol
era
vacc
ines
are
ef
ficac
ious
and
ef
fect
ive
in in
divi
dual
s >1
4 ye
ars o
f age
ag
ains
t cho
lera
.
Page
22
of 2
9
Re
fere
nce
s:
1.
Cl
emen
s JD
et a
l. Fi
eld
tria
l of o
ral c
hole
ra v
acci
nes i
n Ba
ngla
desh
: res
ults
from
thre
e-ye
ar fo
llow
-up
et a
l. La
ncet
199
0; 3
35(8
684)
: 270
-273
. 2.
Ta
ylor
DN
et a
l. Tw
o-ye
ar st
udy
of th
e pr
otec
tive
effic
acy
of th
e or
al w
hole
cel
l plu
s rec
ombi
nant
B
subu
nit c
hole
ra v
acci
ne in
Per
u. JI
D 20
00; 1
81(5
): 16
67-1
673.
3.
Tr
ach
DD e
t al.
Fiel
d tr
ial o
f a lo
cally
pro
duce
d, k
illed
, ora
l cho
lera
vac
cine
in V
ietn
am. L
ance
t 199
7;
349(
9047
): 23
1-23
5.
4.
Sur D
et a
l. Ef
ficac
y an
d sa
fety
of a
mod
ified
kill
ed-w
hole
-cel
l ora
l cho
lera
vac
cine
in In
dia:
an
inte
rim a
naly
sis o
f a c
lust
er-r
ando
mise
d, d
oubl
e-bl
ind,
pla
cebo
-con
trol
led
tria
l. La
ncet
200
9; 3
74:
1694
-170
2.
5.
Bhat
tach
arya
SK
et a
l. 5
year
effi
cacy
of a
biv
alen
t kill
ed w
hole
-cel
l ora
l cho
lera
vac
cine
in K
olka
ta,
Indi
a: a
clu
ster
-ran
dom
ised,
dou
ble-
blin
d, p
lace
bo-c
ontr
olle
d tr
ial.
Lanc
et 2
013;
13(
12);
1050
-105
6.
6.
Saha
A e
t al.
Safe
ty a
nd im
mun
ogen
icity
stud
y of
a k
illed
biv
alen
t (O
1 an
d O
139)
who
le-c
ell o
ral
chol
era
vacc
ine
Shan
chol
, in
Bang
lade
shi a
dults
and
chi
ldre
n as
you
ng a
s 1 y
ear o
f age
. Vac
cine
20
11; 2
9(46
): 82
85-8
295.
7.
De
sai S
N e
t al.
A Ra
ndom
ized,
Pla
cebo
-Con
trol
led
Tria
l Eva
luat
ing
Safe
ty a
nd Im
mun
ogen
icity
of t
he
Kille
d, B
ival
ent,
Who
le-C
ell O
ral C
hole
ra V
acci
ne in
Eth
iopi
a. A
m J
Trop
Med
Hyg
201
5; 9
3(3)
: 527
-53
3.
8.
Qad
ri F
et a
l. Ef
ficac
y of
a S
ingl
e-Do
se, I
nact
ivat
ed O
ral C
hole
ra V
acci
ne in
Ban
glad
esh.
NEJ
M 2
016;
37
4: 1
723-
1732
.
9.
van
Loon
FPL
et a
l. Fi
eld
tria
l of i
nact
ivat
ed o
ral c
hole
ra v
acci
nes i
n Ba
ngla
desh
: res
ults
from
5 y
ears
of
follo
w-u
p. V
acci
ne 1
996;
14(
2): 1
62-1
66.
10. L
ucas
MES
et a
l. Ef
fect
iven
ess o
f Mas
s Ora
l Cho
lera
Vac
cina
tion
in B
eira
, Moz
ambi
que.
NEJ
M 2
005;
35
2: 7
57-7
67.
11
. Iver
s LC
et a
l. Ef
fect
iven
ess o
f rea
ctiv
e or
al c
hole
ra v
acci
natio
n in
rura
l Hai
ti: a
cas
e-co
ntro
l stu
dy
and
bias
-indi
cato
r ana
lysis
. Lan
cet G
loba
l Hea
lth 2
015;
3(3
): 16
2-16
8.
Page
23
of 2
9
Effi
cacy
an
d E
ffec
tive
nes
s, >
14 y
ears
old
, sev
ere
cho
lera
P
op
ula
tio
n: A
dole
scen
ts a
nd a
dults
>14
yea
rs o
f age
In
terv
enti
on
: 2 d
oses
of t
he c
urre
ntly
ava
ilabl
e ki
lled,
who
le-c
ell o
ral c
hole
ra v
acci
nes (
OCV
s)
Co
mp
aris
on
: Pla
cebo
or n
o va
ccin
e/ot
her p
reve
ntio
n an
d co
ntro
l mea
sure
s (e.
g. W
ASH)
O
utc
om
e: C
ases
of s
ever
e ch
oler
a
Wha
t is t
he e
vide
nce
for p
rote
ctiv
e ef
ficac
y an
d ef
fect
iven
ess a
gain
st se
vere
cho
lera
of t
he c
urre
ntly
av
aila
ble
kille
d, w
hole
cell
OCV
s am
ong
indi
vidu
als ≥
14
year
s of a
ge?
Ra
ting
Adju
stm
ent t
o Ra
ting
Qua
lity
of
Evid
ence
No.
of s
tudi
es/s
tart
ing
ratin
g 2
RCT
4
Fact
ors
decr
easin
g co
nfid
ence
Lim
itatio
n in
stud
y de
sign
No
serio
us
0 In
cons
isten
cy
No
serio
us
0 In
dire
ctne
ss
No
serio
us
0 Im
prec
ision
N
o se
rious
0
Publ
icat
ion
Bias
N
o se
rious
0
Fact
ors
Incr
easin
g Co
nfid
ence
Larg
e ef
fect
N
ot a
pplic
able
0
Dose
-res
pons
e N
ot a
pplic
able
0
Anta
goni
stic
bia
s and
co
nfou
ndin
g N
ot a
pplic
able
0
Fina
l num
eric
al ra
ting
of q
ualit
y of
evi
denc
e 4
Sum
mar
y of
Fin
ding
s
Stat
emen
t on
qual
ity o
f evi
denc
e
Evid
ence
supp
orts
a
high
leve
l of c
onfid
ence
th
at th
e tr
ue e
ffect
lies
cl
ose
to th
e es
timat
e of
th
e ef
fect
on
the
heal
th
outc
ome.
Conc
lusio
n
High
leve
l of s
cien
tific
ev
iden
ce th
at th
e cu
rren
tly li
cens
ed o
ral
chol
era
vacc
ines
are
ef
ficac
ious
and
effe
ctiv
e ag
ains
t sev
ere
chol
era
in in
divi
dual
s ove
r 14
year
s of a
ge.
Re
fere
nce
s:
1.
Q
adri,
F e
t al.
Effic
acy
of a
Sin
gle-
Dose
, Ina
ctiv
ated
Ora
l Cho
lera
Vac
cine
in B
angl
ades
h. N
EJM
201
6;
374:
172
3-17
32.
2.
Q
adri
F et
al.
Feas
ibili
ty a
nd e
ffect
iven
ess o
f ora
l cho
lera
vac
cine
in a
n ur
ban
ende
mic
sett
ing
in
Bang
lade
sh: a
clu
ster
rand
omise
d op
en-la
bel t
rial.
Lanc
et 2
015;
386
:136
2-13
71.
Page
24
of 2
9
Effi
cacy
an
d E
ffec
tive
nes
s o
f a
sin
gle
do
se
Po
pu
lati
on
: Non
-pre
gnan
t adu
lts a
nd c
hild
ren
≥ 1
year
old
(Sha
ncho
l/Euv
icho
l/mO
RCVa
x) o
r ≥ 2
yea
rs o
ld
(Duk
oral
) In
terv
enti
on
: Sin
gle
dose
of t
he c
urre
ntly
ava
ilabl
e ki
lled,
who
le-c
ell o
ral c
hole
ra v
acci
nes (
OCV
s)
Co
mp
aris
on
: Pla
cebo
or n
o va
ccin
e/ot
her p
reve
ntio
n an
d co
ntro
l mea
sure
s (e.
g. W
ASH)
O
utc
om
e: C
ases
of c
hole
ra
Wha
t is t
he e
vide
nce
for p
rote
ctiv
e ef
ficac
y an
d ef
fect
iven
ess o
f a si
ngle
dos
e o
f the
cur
rent
ly a
vaila
ble
kille
d, w
hole
cel
l OCV
s am
ong
indi
vidu
als ≥
1 y
ear o
ld?
Ra
ting
Adju
stm
ent t
o Ra
ting
Qua
lity
of
Evid
ence
No.
of s
tudi
es/s
tart
ing
ratin
g 1
RCT/
3
Obs
erva
tiona
l 4
Fact
ors
decr
easin
g co
nfid
ence
Lim
itatio
n in
stud
y de
sign
No
serio
us
0 In
cons
isten
cy
No
serio
us
0 In
dire
ctne
ss
No
serio
us
0 Im
prec
ision
N
o se
rious
0
Publ
icat
ion
Bias
N
o se
rious
0
Fact
ors
Incr
easin
g Co
nfid
ence
Larg
e ef
fect
N
ot a
pplic
able
0
Dose
-res
pons
e N
ot a
pplic
able
0
Anta
goni
stic
bia
s and
co
nfou
ndin
g N
ot a
pplic
able
0
Fina
l num
eric
al ra
ting
of q
ualit
y of
evi
denc
e 4
Sum
mar
y of
Fin
ding
s
Stat
emen
t on
qual
ity o
f evi
denc
e
Evid
ence
supp
orts
a
high
leve
l of c
onfid
ence
th
at th
e tr
ue e
ffect
lies
cl
ose
to th
e es
timat
e of
th
e ef
fect
on
the
heal
th
outc
ome.
Conc
lusio
n
High
leve
l of s
cien
tific
ev
iden
ce th
at th
e cu
rren
tly li
cens
ed o
ral
chol
era
vacc
ines
are
ef
ficac
ious
for a
t lea
st 6
m
onth
s usin
g a
singl
e do
se.
Page
25
of 2
9
Re
fere
nce
s:
1.
Q
adri
F et
al.
Effic
acy
of a
Sin
gle-
Dose
, Ina
ctiv
ated
Ora
l Cho
lera
Vac
cine
in B
angl
ades
h. N
EJM
201
6;
374:
172
3-17
32.
2.
Kh
atib
AM
et a
l. Ef
fect
iven
ess o
f an
oral
cho
lera
vac
cine
in Z
anzib
ar: f
indi
ngs f
rom
a m
ass
vacc
inat
ion
cam
paig
n an
d ob
serv
atio
nal c
ohor
t stu
dy. L
ance
t Inf
Dis
2012
; 12(
11):
837-
844.
3.
W
ierz
ba T
F et
al.
Effe
ctiv
enes
s of a
n or
al c
hole
ra v
acci
ne c
ampa
ign
to p
reve
nt c
linic
ally
-sig
nific
ant
chol
era
in O
dish
a St
ate,
Indi
a. V
acci
ne 2
015;
33(
21):
2463
-246
9.
4.
Iver
s LC
et a
l. Ef
fect
iven
ess o
f rea
ctiv
e or
al c
hole
ra v
acci
natio
n in
rura
l Hai
ti: a
cas
e-co
ntro
l stu
dy
and
bias
-indi
cato
r ana
lysis
. Lan
cet G
loba
l Hea
lth 2
015;
3(3
): 16
2-16
8.
5.
Azm
an A
S et
al.
Effe
ctiv
enes
s of o
ne d
ose
of o
ral c
hole
ra v
acci
ne in
resp
onse
to a
n ou
tbre
ak: a
cas
e-co
hort
stud
y. L
ance
t Glo
b He
alth
. 201
6 N
ov;4
(11)
:e85
6-e8
63.
Page
26
of 2
9
Du
rati
on
of
pro
tect
ion
fo
r at
leas
t 3
year
s
Po
pu
lati
on
: Non
-pre
gnan
t adu
lts a
nd c
hild
ren
≥ 1
year
old
(Sha
ncho
l/Euv
icho
l/mO
RCVa
x) o
r ≥ 2
yea
rs o
ld
(Duk
oral
) In
terv
enti
on
: 2 d
oses
of t
he c
urre
ntly
ava
ilabl
e ki
lled,
who
le-c
ell o
ral c
hole
ra v
acci
nes (
OCV
s)
Co
mp
aris
on
: Pla
cebo
or n
o va
ccin
e/ o
ther
pre
vent
ion
and
cont
rol m
easu
res (
e.g.
WAS
H)
Ou
tco
me:
Cas
es o
f cho
lera
W
hat i
s the
evi
denc
e fo
r pro
tect
ive
effic
acy,
eff
ectiv
enes
s, a
nd d
urat
ion
of th
e cu
rren
tly a
vaila
ble
kille
d,
who
le c
ell O
CVs d
urin
g th
e fir
st 3
yea
rs fo
llow
ing
imm
uniz
atio
n am
ong
indi
vidu
als ≥
1 y
ear o
ld?
Ra
ting
Adju
stm
ent t
o Ra
ting
Qua
lity
of
Evid
ence
No.
of s
tudi
es/s
tart
ing
ratin
g 3
RCT/
2
Obs
erva
tiona
l 4
Fact
ors
decr
easin
g co
nfid
ence
Lim
itatio
n in
stud
y de
sign
No
serio
us
0 In
cons
isten
cy
No
serio
us
0 In
dire
ctne
ss
No
serio
us
0 Im
prec
ision
N
o se
rious
0
Publ
icat
ion
Bias
N
o se
rious
0
Fact
ors
Incr
easin
g Co
nfid
ence
Larg
e ef
fect
2 N
ot a
pplic
able
0
Dose
-res
pons
e N
ot a
pplic
able
0
Anta
goni
stic
bia
s and
co
nfou
ndin
g N
ot a
pplic
able
0
Fina
l num
eric
al ra
ting
of q
ualit
y of
evi
denc
e 4
Sum
mar
y of
Fin
ding
s
Stat
emen
t on
qual
ity o
f evi
denc
e
Evid
ence
supp
orts
a
high
leve
l of c
onfid
ence
th
at th
e tr
ue e
ffect
lies
cl
ose
to th
e es
timat
e of
th
e ef
fect
on
the
heal
th
outc
ome
Conc
lusio
n
High
leve
l of e
vide
nce
that
the
curr
ently
av
aila
ble
oral
cho
lera
va
ccin
es w
ith a
2-d
ose
sche
dule
are
effi
caci
ous
and
effe
ctiv
e fo
r at
leas
t 3 y
ears
am
ong
adul
ts, b
ut n
ot a
mon
g yo
ung
child
ren
1 –
5 ye
ars o
ld.
Page
27
of 2
9
Re
fere
nce
s:
1.
Cl
emen
s JD,
Sac
k DA
, Har
ris JR
et a
l. Fi
eld
tria
l of o
ral c
hole
ra v
acci
nes i
n Ba
ngla
desh
: res
ults
from
th
ree-
year
follo
w-u
p et
al.
Lanc
et 1
990;
335
(868
4): 2
70-2
73.
2.
Bhat
tach
arya
SK,
Sur
D, A
li M
et a
l. 5
year
effi
cacy
of a
biv
alen
t kill
ed w
hole
-cel
l ora
l cho
lera
vac
cine
in
Kol
kata
, Ind
ia: a
clu
ster
-ran
dom
ised,
dou
ble-
blin
d, p
lace
bo-c
ontr
olle
d tr
ial.
Lanc
et 2
013;
13(
12);
1050
-105
6.
3. v
an L
oon
FPL,
Cle
men
s JD,
Cha
krab
orty
MR
et a
l. Fi
eld
tria
l of i
nact
ivat
ed o
ral c
hole
ra v
acci
nes i
n Ba
ngla
desh
: res
ults
from
5 y
ears
of f
ollo
w-u
p. V
acci
ne 1
996;
14(
2): 1
62-1
66.
4.
Seve
re K
, Rou
zier V
, Ang
lade
SB
et a
l. Ef
fect
iven
ess o
f Ora
l Cho
lera
Vac
cine
in H
aiti:
37-
Mon
th
Follo
w-U
p. A
m J
Trop
Med
Hyg
201
6; 9
4(5)
: 113
6-19
42.
5.
Thie
m V
D, D
een
JL, v
on S
eidl
ein
L et
al.
Long
-ter
m e
ffect
iven
ess a
gain
st c
hole
ra o
f ora
l kill
ed w
hole
-ce
ll va
ccin
e pr
oduc
ed in
Vie
tnam
. Vac
cine
2006
; 24(
20):
4297
-430
3.
Page
28
of 2
9
Du
rati
on
of
pro
tect
ion
fo
r at
leas
t 5
year
s
Po
pu
lati
on
: Non
-pre
gnan
t adu
lts a
nd c
hild
ren
≥ 1
year
old
(Sha
ncho
l/Euv
icho
l/mO
RCVa
x) o
r ≥ 2
yea
rs o
ld
(Duk
oral
) In
terv
enti
on
: 2 d
oses
of t
he c
urre
ntly
ava
ilabl
e ki
lled,
who
le-c
ell o
ral c
hole
ra v
acci
nes (
OCV
s)
Co
mp
aris
on
: Pla
cebo
or n
o va
ccin
e/ o
ther
pre
vent
ion
and
cont
rol m
easu
res (
e.g.
WAS
H)
Ou
tco
me:
Cas
es o
f cho
lera
W
hat i
s the
evi
denc
e fo
r pro
tect
ive
effic
acy,
eff
ectiv
enes
s, a
nd d
urat
ion
of th
e cu
rren
tly a
vaila
ble
kille
d,
who
le c
ell O
CVs d
urin
g th
e fir
st 5
yea
rs fo
llow
ing
imm
uniz
atio
n am
ong
indi
vidu
als ≥
1 y
ear o
ld?
Ra
ting
Adju
stm
ent t
o Ra
ting
Qua
lity
of
Evid
ence
No.
of s
tudi
es/s
tart
ing
ratin
g 1
RCT/
1
Obs
erva
tiona
l 4
Fact
ors
decr
easin
g co
nfid
ence
Lim
itatio
n in
stud
y de
sign
Serio
us1
-1
Inco
nsist
ency
N
o se
rious
0
Indi
rect
ness
N
o se
rious
0
Impr
ecisi
on
Serio
us2
-1
Publ
icat
ion
Bias
N
o se
rious
0
Fact
ors
Incr
easin
g Co
nfid
ence
Larg
e ef
fect
2 N
ot a
pplic
able
0
Dose
-res
pons
e N
ot a
pplic
able
0
Anta
goni
stic
bia
s and
co
nfou
ndin
g N
ot a
pplic
able
0
Fina
l num
eric
al ra
ting
of q
ualit
y of
evi
denc
e 2
Sum
mar
y of
Fin
ding
s
Stat
emen
t on
qual
ity o
f evi
denc
e
Evid
ence
supp
orts
a
limite
d le
vel o
f co
nfid
ence
that
the
true
effe
ct li
es c
lose
to
the
estim
ate
of th
e ef
fect
on
the
heal
th
outc
ome
Conc
lusio
n
Low
leve
l of e
vide
nce
that
the
curr
ently
av
aila
ble
oral
cho
lera
va
ccin
es w
ith a
2-d
ose
sche
dule
are
effi
caci
ous
and
effe
ctiv
e fo
r at
leas
t 5 y
ears
. 1
High
rate
of l
oss t
o fo
llow
-up.
2Do
wng
rade
d as
ther
e w
ere
smal
l sam
ple
sizes
incl
uded
in th
e st
udie
s to
asse
ss th
e ou
tcom
e of
dur
atio
n of
pro
tect
ion.
Page
29
of 2
9
Re
fere
nce
s:
1.
Bh
atta
char
ya S
K, S
ur D
, Ali
M e
t al.
5 ye
ar e
ffica
cy o
f a b
ival
ent k
illed
who
le-c
ell o
ral c
hole
ra v
acci
ne
in K
olka
ta, I
ndia
: a c
lust
er-r
ando
mise
d, d
oubl
e-bl
ind,
pla
cebo
-con
trol
led
tria
l. La
ncet
201
3; 1
3(12
); 10
50-1
056.
2.
van
Loo
n FP
L, C
lem
ens J
D, C
hakr
abor
ty M
R et
al.
Fiel
d tr
ial o
f ina
ctiv
ated
ora
l cho
lera
vac
cine
s in
Bang
lade
sh: r
esul
ts fr
om 5
yea
rs o
f fol
low
-up.
Vac
cine
199
6; 1
4(2)
: 162
-166
.