MPG 2014 03 20 Guarino jpgn-14-202 sdc1

ESPGHAN/ESPID Guidelines for the Management of AGE in Children in Europe
RISK FACTORS FOR SEVERE AND/OR PERSISTENT DISEASE
Table 1.1. Is there a relationship between severe or persistent diarrhea and etiology?
Reference Study Period of QoS Country In/Out Population Randomization Intervention Comparison FU n/N ITT Outcomes RCT n Effect Effect Comments
type observation Patients measures measure size
(95% CI)
Shai S, Surveillance Between + Germany Inpatients N= 130 — Survey on — — No No. of severe — Number 17/101 RV infection
2013 system April 2009 children hospital RV can have a life-
and March younger discharge gastroenteri threatening
2011 than 17 data tis (N° course
years with nosocomial)
very severe Incidence of Incidence 1.2/100,000/
RV very severe rates year
gastroenteri RV diarrhea ( 0.9–
tis (101 were in children 1.4/100,000)
verified) less than 5
years of age;
Valentini D, Prospective March 2010 + Italy Inpatients N=232 — Collection of Coinfections 232/275 No Max. no of — OR (95%CI) 8.79 Coinfection
2013 cohort study to April 2011 between 1 clinical data vs diarrhea (3.32;23.28) p with different
month and and stool Monoinfectio stools/24 h <0.001 pathogens is
16 years of samples ns (≥6) associated with
age Duration of 3.81 (1.47;9.86) a more severe
admitted for diarrhea p= 0.006 course of
AGE (days) (≥5) symptoms
Duration of 7.11
vomiting (2.74;18.42)
(days) (≥3) p<0.001
Fever (≥38°) 17.78
(2.32;136.17)
p=0.006
Severe 28.70
dehydration (3.04;270.6)
(%) p=0.003
Friesema Case-control May 2008 to + The Inpatients N=144 (+63 — Collection of Diarrhea vs 143/144 No Pathogens — Rates Virus: Importance of
IH, 2012 study November Netherlan controls) clinical data not diarrhea isolated from 50/51(98%) [RV viral pathogens,
2009 ds children 0 - and stool children (0- 65%, Adeno especially RV,
15 yr (73% samples 1yr) 31%, NV 23%]; in
being hospitalized Bacteria 12/51 hospitalizations
<2 yr), with (23%) of children with
admitted for gastroenteri [Campylobacter gastroenteritis.
severe AGE tis (N=51) 4%, EPEC 16%,
EAEC 4%];
Parasites 0%
Pathogens Rates Virus:

isolated from 21/23(91%) [RV
children (1- 70%, Adeno
2yr) 13%, NV 10%];
hospitalized Bacteria 7/23
with (30%)
gastroenteri [Salmonella
tis (N=23) 10%, EPEC
13%]; Parasites
10%
Pathogens Rates Virus: 7/16
isolated from (44%) [RV 31%,
children (2- Adeno 12%, NV
4yr) 7%]; Bacteria
hospitalized 8/16 (50%)
with [Salmonella
gastroenteri 31%]; Parasites
tis (N=16) 31%
Pathogens Rates Virus: 1/6 (17%)
isolated from [RV 17%];
children Bacteria 4/6
(>4yr) (67%)
hospitalized [Salmonella
with 50%]; Parasites
gastroenteri 20%
tis (N=6)
Consumption OR (95%CI) 4.25; (1.06–
of eggs 17.06) p<0.05
Consumption OR (95%CI) 0.08; (0.01–
of fish 0.97) p<0.05
Oldak E, Prospective July 2009 + Poland Inpatients N=242 — Collection of RV vs NV 242/242 Yes Isolation of — Rates RV 51/242 NV are a
2012 cohort study and June children clinical data infections pathogens (21.1%) vs NV relevant cause
2010 <5yr of age and stool 35/242 (14.5%) of acute,
admitted for samples Duration of Rates RV 11/51 community
AGE diarrhea (≥6 (21.6%) vs NV acquired
days) 4/35 (11.4%)p= gastroenteritis
0.17 in Polish
Severity Rates RV 22/51 (43%) children
score vs NV 5/35
(severe) (14.3%) p<0.01
Ogilvie I, Scoping review — — Western Inpatients 76 studies — — Community — — Patients with 2 (n=3734; Rates (%) 42.6% RV
2012 Europe from 16 acquired vs severe n=251) gastroenteritis
countries on Nosocomial nosocomial is a common
European diarrhea RVGE in disease
children <5 France, Italy, associated with
yr of age Spain and significant
with the UK morbidity and
community- Patients with Rates (%) 24.4%, 30.2% costs

acquired and severe and 40% across Western
nosocomial nosocomial Europe
diarrhea RVGE in
Austria,
Germany,
and
Switzerland
Severe 2 (Ireland Rates (%) 80% vs 55%
dehydration n=663; (Ireland) 10.8%
in children Sweden vs 0.8%
with n=984) (Sweden)
community-
acquired vs
nosocomial
gastroenteri
tis
Mortality 1(n=10,99 Incidence 0.74 per
due to 0) rates 100,000 vs 0.16
nosocomial per 100,000
RVGE (< vs >
12mo)
Lorrot M, Prospective November + France Inpatients N=457 — Collection of RV vs NV 457/457 Yes Isolation of — Rates RV 77 (43.5%) NV are the
2011 cohort study 2001 to May children 0- clinical data infections pathogens NV 15 (8.5%) second leading
2004 15 yr of age and stool (0-6mo) Bacteria 8 (4%) causative agent
admitted for samples N=177 of
severe AGE Isolation of Rates RV 63 (59.4%) gastroenteritis
(Patients pathogens NV 10 in hospitalized
with chronic (6-12mo) (9.4%)Bacteria young children
diarrhea >10 N=106 2 (2%) and such
days were Isolation of Rates RV 59 (57.8%) infections are
excluded) pathogens NV 8 (7.8%) less severe
(12-24mo) Bacteria 4 (4%) than those
N=102 caused by RV
Isolation of Rates RV 22 (44.9%)
pathogens NV 3 (6.1%)
(24-60mo) Bacteria 6 (12%)
N=49
Isolation of Rates RV 4 (17.4%) NV
pathogens 2 (8.7%)
(>60mo) Bacteria 5 (20%)
N=23
Length of Median ± SD 3.02 (1.54) 1.85
hospitalizatio (1.03) p<0.001
n (days) (RV
vs NV)
Severity Median ± SD 12.6 (2.92)
score 10.47 (2.83)
(Vesikari) RV p<0.001
vs NV
Intravenous Rates 172 (77.13%) 21

rehydration (55.26%)
(%) RV vs NV p=0.005
(N=261,
mixed
infections
excluded)
Mrukowicz Retrospectiv 1994-96 + Poland Inpatients N=953 — Hospital RV vs not RV — — Severe — Rates 94% (61.6% of RV is a leading
JZ, 1999* e cohort children discharge clinical cases younger aetiological
study hospitalized data conditions than five years) agent of severe
for AGE (Vesikari p<0.001 gastroenteritis
score >11) in in young
children with children in
RV Poland and that
associated the burden of
diarrhea this infection is
Duration of Median ± SD 9.5 d (+/-9.8 d) significant
hospitalizatio (1999)
n (days)
*Ogilvie 2011 (systematic review) cited this study and concluded that data on the burden of RVGE in terms of mortality, morbidity and economic burden is limited for Central and Eastern Europe.
Rimoldi SG, Prospective January + Italy Inpatients N=273 — Clinical data Different — — Severe — Median ± SD RV 2.9±2.8 vs The severity of
2011 cohort study 2008 to children, and stool viruses- clinical NV 3.1±3.5 AdV-associated
October suffering samples associated conditions Boca 11.5±4.5 infection was
2009 from acute diarrhea (Vesikari Adeno 0.2 lower than for
gastroenteri score) in (Adeno vs NoV, HRV and
tis, in the children 1- others p<0.001) HBoV.
age range 18mo with
from 0 to diarrhea
222 mo
Gimenez- Prospective January, + Spain Inpatients N=1192 — Clinical data RV (n = 584) — — Severe — Median ± SD 14.2 (3.8) vs RV is the
Sanchez F, cohort study February children and stool vs not RV (n = clinical 11.0 (4.2) primary causal
2010 and March <5yr of age samples 503) conditions p<0.001 agent of AGE in
of 2006 (Merck scale) children under
in children the age of 2
<5yr with years in Spain
diarrhea and that it
Severe Rates 30% vs 12% produces a
clinical p<0.001 more severe
conditions manifestation
(Merck scale)
in children
<5yr with
diarrhea
Severe Rates 51 (20.2%) 10
dehydration (11%) NS
(degree >6%)
Wiegering Retrospectiv April 1, 2005 + Germany Inpatients 650 charts of — — Comparisons — — Duration of — Mean 3.4±0.1 vs Children with
V, 2011 e cohort to May 31, children between all diarrhea (all number ±SD 6.1±0.4, viral infection
study 2008 with AGE. viral viral vs p<0.001 had
262 (43.8%) infections and Salmonella) significanlty
had RV, 188 Salmonella Diarrhea mean 3.8±0.1 vs more

(31.4%) NV, infection events (all number ±SD 10.4±0.5, respiratory
58 (9.7%) viral vs p<0.001 associated
AV, 47(7.9%) Salmonella) symptoms and
Salmonella. Vomiting mean 2.6±0.2 vs vomiting, but
events (all number ±SD 1±0.4, p<0.001 less episodes of
viral vs diarrhea and
Samonella) total duration
Airway mean 1.8±0.1 vs of diarrhea
inflammation number ±SD 0.6±0.3; when
score (all p<0.001 compared to
viral vs children with
Salmonella) Salmonella
Gastroenteri mean All viral infection.
tis score (all number ±SD 12.7±0.1 vs
viral vs Salmonella
Samonella 13.4±0.5, p=NS;
and RV vs AV RV 13.5± 0.2 vs
and NV) AV and NV
11.9± 0.2 and
11.5±0.4 ,
p<0.001
Muhsen K, MA 1970s ++ Developin Inpatients N=17030 — Detailed Acute vs — — Association 4 case- OR (95%CI) 3.18 (1.50-6.76) G. lamblia was
2009 through g and mostly <6yr clinical persistent between control, 1 p<0.0001 not associated
2009 countries Outpatien of age (1 history and diarrhea vs Giardia cohort with acute
ts case-control laboratory controls Lamblia and study diarrhea.
study 0-14 investigation PD However,
yr; 1 case- s Association OR (95%CI) 0.60 (0.38-0.94) limited data
control between p=0.03 suggest that
study all Giardia initialGiardia
ages); 13 Lamblia and infections in
case-control AD early infancy
studies and may be
2 cohort positively
studies associated with
diarrhea. Meta-
analysis of 5
persistent
diarrhea
studies showed
a positive link
with Giardia
Abba K, Systematic Search date: ++ Developin Inpatients N=3832 — Sample Persistent — — RV Weighted PD 5% vs no There is no
2009 review May 20, g and children stools Diarrhea vs mean diarrhea 3% evidence that
2008 (none countries Outpatien <6yr of age no diarrhea percentage any particular
after 2000) ts Enteric Weighted PD 5% vs no pathogen or
Adenovirus mean diarrhea 1% type of
percentage pathogen is
Campylobact Weighted PD 6% vs no associated with

er mean diarrhea 8% persistent
percentage diarrhea in
Shigella 7 (680 Weighted PD 4% vs no children under
cases and mean diarrhea 2% the age of six in
1021 percentage low and middle
controls) income
Salmonella 6 (510 Weighted PD 4% vs no countries.
cases and mean diarrhea 0% There is
857 percentage therefore no
controls) evidence to
Vibrio 3 (405 Weighted PD 0% vs no justify routine
Cholerae cases and mean diarrhea 1% antimicrobial
813 percentage use for children
controls) with persistent
EPEC 7 (550 Weighted PD 41% vs no diarrhea of
cases and mean diarrhea 30% unknown
604 percentage cause, in
controls) keeping with
EHEC 2 Weighted PD 0% vs no current
(143cases mean diarrhea 0% guidelines.
and 143 percentage
controls)
Giardia 8 Weighted PD 10% vs no
(688cases mean diarrhea 7%
and 1062 percentage
controls)
Cryptosporid 0
ium
Entamoeba 5 (688 Weighted PD 2% vs no
histolytica cases and mean diarrhea 3%
1063 percentage
controls)
Ochoa TJ, Prospective September- + Perù Outpatien N=1034 Controls were A field Diarrhea vs 992/103 No Duration of — Mean±SD 7.1 ± 6.1 Persistent
2009 cohort study 2006 and ts children selected worker not diarrhea 4 diarrhea in (children < diarrhea was
December- from 2 to 12 randomly* visited accordance 6mo) vs 4.9 ± more frequent
2007 months of control to age* 3.8 (children ≥ in infants <
age children at 6mo) 6mo of age. No
home to Persistent Rates 13.5% (children specific
collect stool diarrhea** < 6mo) vs 3.6% bacterial
samples. A (children ≥ species was
field worker 6mo) associated with
visited Isolation of Rates 14.1% (12/85) persistent
children EAEC in stool diarrhea
with coltures in
diarrhea at children with
home at persistent
least once a diarrhea
week until Isolation of Rates 7.9% (3/38)

the episode EPEC in stool
ended. coltures in
children with
persistent
diarrhea
Isolation of Rates 15% (3/20)
DAEC in stool
coltures in
children with
persistent
diarrhea
Isolation of Rates 18.8% (3/16)
ETEC in stool
coltures in
children with
persistent
diarrhea
Campylobact
er in stool
coltures in
children with
persistent
diarrhea
Roatvirus in
stool
coltures in
children with
persistent
diarrhea
mixed
pathogens in
children with
persistent
diarrhea
*not specified how
**diarrhea lasting > 14 days was considered persistent
Rivera FP, Prospective 26 months + Perù Outpatien N=1873 — Collection of Diarrhea vs NO No Clinical and — Rates Isolated ETEC The duration of
2010 cohort study (September ts (1129 cases stool not diarrhea epidemiologi strains in cases diarrhea caused
2006-July and 744 samples cal (60/1129; 5.3%) by ETEC-LT
2008) controls) characteristi and controls strains tended
children 2- cs of ETEC (32/744 ; 4.3%) to be longer
24 months diarrhea Persistent (up to 24 days).
of age diarrhea*
(single ETEC
strain, N=38):
11%
Persistent
diarrhea (all
ETEC isolates
N=60): 8%
Presence of Rates Persistent
ST (heat- diarrhea (ETEC-
stable toxin) LT strain,
and LT (heat- N=31): 6%
labile toxin) Persistent
diarrhea (ETEC-
ST isolates
N=15): 0%*
*diarrhea lasting > 14 days was considered persistent
Moore SR, Prospective 127 months ++ Brazil Outpatie N=414 — Nurses visit Diarrhea vs 414/414 Yes Isolation of — Rates 12/98 (12.2%) Shigella and
2010 cohort study (August nts children ≤ 5 home of not diarrhea Cryptosporid vs 15/289 Cryptosporidiu
1989-March years of age each ium species (5.2%) m are
2000) and newborn in stool significantly
newborns child 3 times coltures associated with
between a week for Isolation of Rates 7/132 (5.3%) vs prolonged
August 1989 the first 45 Ascaris 61/442 (13.8%) episodes* of
and March mo. Then species in diarrhea, and
2000 twice a stool both of them
week. coltures are related with
Children Isolation of Rates 16/132 (12.1%) growth
with bacteria in vs 8/442 (1.8%) faltering,
diarrhea stool especially in
were visited coltures (all tropical and
daily species) developing
Isolation of Rates 6/132 (4.5%) vs regions. Ascaris
Shigella 5/440 (1.1%) and multiple
species in pathogens
stool were found to
coltures be more
Fecal Rates 67/132 (50.8%) frequent in
Leukocytes vs 28/442 controls than in
(6.3%) children with
Lactoferrin Rates 27/35 (77.1%) persistent
vs 47/95 diarrhea**, due
(49.5%) to a possible
Multiple Rates 26/98 (26.5%) mitigating
pathogens vs 82/194 effect on the
(40.7%) duration of
intestinal
infections by
altering
immune
response.
*Prolonged diarrhea= 7-13th day
**Diarrhea lasting > 14 days was considered persistent
Allison GM, Case-control — + Banglades Inpatients N=92 — Detailed Positive for 50/92 No N° of — Rates 37% (18/47) vs In Bangladesh,
2011 study h children clinical Cryptosp. vs (33 persistent 0% (0/39) where
diarrhea (46 s Antibody Median 68 [28; 110] vs with persistent

controls (IgG) levels [25th-75th 4 [0; 10] diarrhea*.
with to percentiles] Although the
negative Cryptosporid dominant
stool ium parvum antibody
coltures for gp15 (Initial- response
Cryptosporid follow-up appears to be
ium; period) targeted to
subsequentl Antibody Median −29 [–97; 13] vs conserved
y 7 controls (IgM) levels [25th-75th 0 [–; 0] peptide
were founf to percentiles] epitopes of
positive for Cryptosporid g15, antibody
PCR and ium parvum responses to
were thus gp15 (Initial- polymorphic,
considered follow-up species- or
cases) period) subtype specific
Antibody Median 83 [19; 243] vs epitopes may
(IgA) levels [25th-75th 40 [3; 61] also occur.
to percentiles] These findings
Cryptosporid have
ium parvum implications for
gp15 (Initial- development of
follow-up gp15 as a
period) putative
Antibody Median 62 [19; 124] vs vaccine
(IgG) levels [25th-75th 0 [–7; 7] candidate
to percentiles]
Cryptosporid
ium hominis
gp15 (Initial-
follow-up
period)
Antibody Median 2 [–20; 20] vs 0
(IgM) levels [25th-75th [–7; –8]
to percentiles]
Cryptosporid
ium hominis
gp15 (Initial-
follow-up
period)
Antibody Median 50 [10; 138] vs
(IgA) levels [25th-75th 4 [–1; 24]
to percentiles]
Cryptosporid
ium hominis
gp15 (Initial-
follow-up
period)
*Diarrhea lasting > 14 days was considered persistent
AGE= Acute gastroenteritis; AV= Adenovirus; DAEC= diffusely adherent Escherichia coli; EAEC=Enteroaggregative Escherichia coli; EPEC=enteropathogenic
Escherichia coli; ETEC= Enterotoxigenic Escherichia coli; LT=heat-labile toxin; NV= Norovirus; OR=odd ratio; QoS=Quality of Study; RV=Rotavirus; RVGE=
Rotavirus gastroenteritis; SD=standard deviation; ST= heat-stable toxin.
1.2. Is there a relationship between host-related factors and risk of severe or persistent diarrhea?
Table 1.2.1. Risk factor: younger age
Reference Study type Period of Qo Country In/Out Population Intervention Comparison FU n/N ITT Outcomes measures Effect Effect size Comments
observation S Patients measure
Friesema IH, Case- May 2008 + The Inpatients N=144 (+63 Collection of Diarrhea vs 143/144 No Pathogens isolated Rates Virus: 50/51(98%) Importance of viral
2012 control to Netherland controls) children clinical data not diarrhea from children (0- [RV 65%, Adeno pathogens, especially
study November s 0 -15 yr (73% and stool 1yr) hospitalized 31%, NV 23%]; RV, in hospitalizated
2009 being <2 yr), samples with gastroenteritis Bacteria 12/51 children with
admitted for (N=51) (23%) gastroenteritis
severe AGE [Campylobacter
4%, EPEC 16%,
EAEC 4%];
Parasites 0%
Pathogens isolated Rates Virus: 21/23(91%)
from children (1- [RV 70%, Adeno
2yr) hospitalized 13%, NV 10%];
with gastroenteritis Bacteria 7/23
(N=23) (30%) [Salmonella
10%, EPEC 13%];
Parasites 10%
Pathogens isolated Rates Virus: 7/16 (44%)
from children (2- [RV 31%, Adeno
4yr) hospitalized 12%, NV 7%];
with gastroenteritis Bacteria 8/16
(N=16) (50%) [Salmonella
31%]; Parasites
31%
Pathogens isolated Rates Virus: 1/6 (17%)
from children (>4yr) [RV 17%];
hospitalized with Bacteria 4/6
gastroenteritis (N=6) (67%) [Salmonella
50%]; Parasites
20%
Lorrot M, 2011 Prospective November + France Inpatients N=457 children 0- Collection of Comparing 457/457 Yes Isolation of Rates RV 77 (43.5%) NV Main role of RV in
cohort 2001 to 15 yr of age clinical data children pathogens (0-6mo) 15 (8.5%) hospitalized
study May 2004 admitted for and stool basing on N=177 Bacteria 8 (4%) gastroenteritis among
severe AGE samples clinical Isolation of Rates RV 63 (59.4%) NV Frenchchildren less
(Patients with conditions pathogens (6-12mo) 10 (9.4%)Bacteria than 2 years of age
chronic diarrhea and age N=106 2 (2%)
>10 days were Isolation of Rates RV 59 (57.8%) NV

excluded) pathogens (12- 8 (7.8%) Bacteria
24mo) N=102 4 (4%)
Isolation of Rates RV 22 (44.9%) NV
pathogens (24- 3 (6.1%) Bacteria
60mo) N=49 6 (12%)
Isolation of Rates RV 4 (17.4%) NV 2
pathogens (>60mo) (8.7%) Bacteria 5
N=23 (20%)
Lenght of Median ± RV 3.26 (±1.84)
hospitalization SD NV 2.17 (±1.06)
(days) in children 0- p=0.0293
6 mo (RV vs NV)
(days) in children 6- p=0.0013
24 mo (RV vs NV)
(days) in children p=0.0078 3.02
>24mo (RV vs NV)
Lenght of Median ± 3.02 (1.54) 1.85
hospitalization SD (1.03) p<0.001
(days) (RV vs NV)
Severity score Median ± NS
(Vesikari) in children SD
0-6 mo (RV vs NV)
Severity score Median ± 13.48 (±2.54)
(Vesikari) in children SD 11.39 (±3.05)
6-24 mo (RV vs NV) p<0.002
Severity score Median ± 12.88 (±2.94) 8.8
(Vesikari) in children SD (±2.28) p=0.007
24 mo (RV vs NV)
Intravenous Rates NS
rehydration (%) in
children 0-6mo; RV
vs NV (N=261, mixed
infections excluded)
Intravenous Rates 107 (87.7%) 12
rehydration (%) in (66.67%) p=0.031
children 6-24mo; RV
vs NV (N=261, mixed
Intravenous Rates NS
rehydration (%) RV
vs NV (N=261, mixed
Moore SR, Prospective 127 months ++ Brazil Outpatient N=414 children ≤ Nurses visit Diarrhea vs 414/414 Yes Age-specific attack Rates Total, AD, and PD Infants with Prolonged
2010 cohort (August s 5 years of age and home of each not diarrhea rates all peaked at 6-12 diarrhea have a higher
study 1989-March newborns newborn child 3 months of age risk of developing PD in
2000) between August times a week (5.15, 4.22, and later childhood. *
1989 and March for the first 45 0.68 episodes per
2000 mo. Then twice child-year,
a week. respectively).
Children with Children with PD Rates 57/71 (80.3%);
diarrhea were who experienced 30/57 (52.6%)
visited daily also ProD episode;
children in the first
year of life
Risk to develop PD OR 2.2, 95% CI;
in children who [1.32-3.54],
experienced ProD in P=0.002
their first year of life
*Prolonged diarrhea= 7-13th day, diarrhea lasting > 14 days was considered persistent
Pathela P, 2006 Prospective 1993-1996 + Bangladesh Outpatient N= 252 children < Door-to-door Age groups 244/252 YE Risk to develop PD Incidence 0.4 (45); p < Significant differences
cohort s 5yr of age census S (n° episodes per Rates 0.001 between 0 /5-month
study conducted by child year) in age groups and all
community children 0-5 mo other age groups
health workers Risk to develop PD OR (95%CI) 0.59 (0.48 /0.73); When adjustment for
in children 18-23 mo p<0.001 other
covariates was done,
the relative odds of
diarrhea in the older
age groups were lower
compared to the
youngest age group.
Pereira AL, Case- Not + Brasil Inpatients N=261 (134 cases Collection of Acute vs — YE Detection of EAEC Rates CVD432+ : Acute The age-stratified
2007 control specified and 127 controls) stool samples persistent S virulance markers in (11.1%) analyses showed that
study ≤ 5 years of age; diarrhea vs fecal samples Persistent (23.9% different CVD432-
controls were controls %) Controls related genotypes were
defined as (9.7%) in children associated with
children who did < 12 mo of age vs persistent diarrhea in
not present with Acute (6.7%) the 2 groups studied.
diarrhea in the 4 Persistent CVD432+ strains were
weeks before (20.9%) Controls associated with
sample collection (12.7%) in persistent diarrhea in
children > 12 mo children <12 months of
of age age, whereas,
Detection of EAEC Rates CVD432+ : Acute inchildren >12 months

specific genotypes in (6.8%) Persistent of age, the genotype
fecal samples (15.2%%) associated with
Controls (3.8%) in protracteddiarrhea was
children < 12 mo CVD432+EAST1+
of age vs Acute
(3.8%) Persistent
(9.3%) Controls
(8.1%) in children
> 12 mo of age
Rates EAST1+ : diarrhea
(13%) and
controls (4%) in
children 6-12 mo
of age vs
diarrhea (8.2%)
and controls
(4.2%) in children
< 6 mo of age
Mukhopadhyay Case- 71 months + Nepal Inpatients N=508 < 5 years of Collection of Persistent — NO Rates of intestinal Rates 13.8%, 19.3%, In each age group, the
C, 2007 control (April 1998- age (253 children stool samples diarrhea vs protozoal infections 25.2%, and 33.2% rate of infection was
study March with persistent acute in age groups (6-11; significantly higher
2004) diarrhea, 155 with diarrhea vs 12-23; 24-35; 36-60) than the previous age
acute diarrhea controls* group.
and 100 controls)

Moyo SJ, 2007 Prospective December + Tanzania Inpatients N=218 children Detailed clinical Age groups — YE Detection of EAEC Rates EAEC: 0-6mo EAEC and EPEC were
cross- 2005 to <5yr of age, history and S strains in children 27.5%; 7-12mo significantly more
sectional February admitted for laboratory with 15.6%; 13-24 6%; prevalent among the
study 2006. acute/persistent investigations acute/persistent 25-60mo 7.4% age group 0–6 months
diarrhea diarrhea
Detection of EPEC Rates EPEC: 0-6mo
strains in children 13.7%; 7-12mo
with 3%; 13-24 3%; 25-
acute/persistent 60mo 0%
diarrhea
Ochoa TJ, 2009 Prospective September- + Perù Outpatient N=1034 children A field worker Diarrhea vs 992/1034 NO Duration of diarrhea Mean±SD 7.1 ± 6.1 (children Persistent diarrhea was
cohort 2006 to s from 2 to 12 visited control not diarrhea in accordance to age < 6mo) vs 4.9 ± more frequent in
study December- months of age children at 3.8 (children ≥ infants < 6mo of age.**
2007 home to collect 6mo); p< 0.0001
stool samples. Persistent diarrhea Rates 13.5% (children <
A field worker 6mo) vs 3.6%
visited children (children ≥ 6mo);
with diarrhea at p< 0.0001
home at least Passive surveillance Incidence 1.26 (children < 6

once a week diarrhea incidence, Rates mo) vs 0.85
until the episodes/child/year (children ≥ 6mo);
episode ended. p=0.0018
Isolation of RV in Rates 24/434 (5.9%) vs
children with 137/530 (28.1%)
persistent diarrhea
<6mo and ≥ 6mo of
age
*not specified how
**diarrhea lasting > 14 days was considered persistent
Rivera FP, 2010 Prospective 26 months + Perù Outpatient N=1873 (1129 Collection of Diarrhea vs — NO Clinical and Rates Isolated ETEC The incidence of ETEC
cohort (September s cases and 744 stool samples not diarrhea epidemiological strains in cases diarrhea in our sample
study 2006-July controls) children characteristics of (3.4%) and was significantly more
2008) 2-24 months of ETEC diarrhea controls 1.2%) < frequent in children >
age 12 mo of age vs 12 months of age than
cases (14.5%) and in younger children*
controls (8.4%) >
12 mo of age
Umamaheswar Case- 17 mo, + India Inpatients N=120 children Detailed clinical Persistent vs 55/120 - YE Children with PD Rates PD 30/60(50%) vs Persistent diarrhea was
i B, 2010 control November from 1 mo. to 10 history and acute 3 months S and AD < 1yr AD 37/60 (61.7%) more frequent in
study 2000-April yr. of age with laboratory diarrhea Children with PD Rates PD 29/60(48.4%) infants <5yr of age*
2002 persistent* or investigations and AD 1-5yr vs AD 22/60
acute diarrhea (36.7%)
Children with PD Rates PD 1/60(1.6%) vs
and AD >5yr AD 1/60 (1.6%)
Children with PD Rates 5/60 (8.3%)
who died (all <5yr of
age)
Sutra S, 2012 Cross- 2011 + Thailand Inpatients Children < 5yr of The authors — — Yes Persistent diarrhea N° of 202 episodes (1.6 age, sepsis, anemia,
sectional age investigated the episodes per 1,000 chronic diseases,
study number of OPD and rates admissions) malnutrition and HIV
visits (756,552; Risk factors related Multivariate age, sepsis, are related to
1:5 ), IPD to PD analysis anemia, chronic persistent diarrhea
(124,403 diseases,
admissions; malnutrition and
1:30) HIV.
Strand TA, Prospective June 1998 + Nepal Outpatient N=335 children 6- Study — 334/335 — Risk of persistent OR (95%CI) 17.0 (3.5, 83.1) The odds of prolonged
2012 cohort to s 35 mo of age physicians diarrhea in children illness was 9.3-fold
study September undertook the 6-11 mo of age higher if a child was not
2000 initial interview Risk of persistent OR (95%CI) 9.3 (2.4, 35.7) breastfed, this effect
and clinical diarrhea in not was not modified by
examination, breast fed children age. This is an
while trained argument for
field workers recommending
visited the breastfeeding, also
homes for beyond infancy in
follow-up every populations where
fifth day until childhood diarrhea is
recovery common.
AD= Acute diarrhea; AGE= Acute gastroenteritis; EAEC=Enteroaggregative Escherichia coli; EPEC=enteropathogenic Escherichia coli; ETEC= Enterotoxigenic
Escherichia coli; NV= Norovirus; PD= Persistent diarrhea; ProD= Prolonged diarrhea; QoS=Quality of Study; RV=Rotavirus; SD=standard deviation.
Table 1.2.2. Risk factor: Feeding practice

Reference Study type Period of Qo Country In/Out Population Intervention Comparison FU n/N ITT Outcomes Effect Effect size Comments
observation S Patients measures measure
Morales Population- 2 years + Spain Outpatient 580 children (131 Active No Incidence of AGE OR (95%CI) Risk of AGE 4- Risk of gastroenteritis
E, 2012 based s never breastfed, 75 surveillance and from birth to 6 6m = 0.34 in other age ranges
cohort brestfed for less 2 m, evaluation of months and 7-14 (0.18-0.64) Risk seems to be not
97 for 2-4m, 215 for risk of months and of recurrency significantly reduced by
4-6 m, 62 for more Wheezing, PRTIs, incidence or 4-6m= 0.37 brestfeeding.
than 6 m) atopic eczema recurrent AGE (0.17-0.77)
and
gastroenteritis
Moore Prospective 127 months ++ Brazil Outpatient N=414 children ≤ 5 Nurses visit Diarrhea vs not 414/414 Ye Age at weaning Linear positive early weaning was
SR, 2010 cohort (August s years of age and home of each diarrhea s from exclusive correlation correlation associated with earlier
study 1989-March newborns between newborn child 3 breastfeeding with age at first onset of Prolonged
2000) August 1989 and times a week for ProD episode diarrhea*
March 2000 the first 45 mo. (Spearman's
Then twice a ρ=0.309;
week. Children P=0.005)
with diarrhea
were visited
daily
*Prolonged diarrhea= 7-13th day
Morrow Prospective 1988–1991 + US Outpatient N=93 children up to Mother–infant Groups (low, 93/93 Ye Consumption of Poisson p= 0.004 Breast-feeding conveys
AL, 2005 cohort s 2yr of age and their pairs were intermediate, s high levels of 2 -FL regression natural anti-infective
study mothers followed from high) of specific as a percentage of compounds tothe child
birth up to 2 y and total 1,2- milk and is the most
postpartum with linked milk oligosaccharide effective intervention
weekly oligosaccharides (protection against currentlyknown for
collection of (mmol/L) Campylobacter) preventing morbidity
infant stool and Consumption of Poisson p= 0.012 and mortality, caused

infant high levels of regression byinfectious disease in
feedingand LDFH-I as a young children
illness data percentage of milk
oligosaccharide
(protection against
Calicivirus)
Consumption of Poisson p<0.0001
high levels of total regression
2-linked
oligosaccharide as
a percentage of
milk
oligosaccharide
(protection against
severe diarrhea)
Content of 2- Means±SD Children with
linked diarrhea and
oligosaccharides in ST-coli
children infection: 3.9 ±
whocontracted ST- 0.7 SE (n = 4);
associated children
diarrhea while without
breast-feeding diarrhea
infected by ST-
coli (7.6 ± 1.0,
n= 43);
uninfected
controls (7.5 ±
1.0,n = 46) (P
<0.01)
Manger Prospective February + India Outpatient N=2296 children 6- Detailed clinical — 2296/2296 Ye Risk for PD in OR (95%CI) 0.56 (0.37, Breast feeding is
MS, 2011 cohort 1998- s 30 mo of age history and s breast-fed children 0.83) p= 0.004 protective against PD
study September laboratory
2000 investigations
Allison Case- — + Banglades Inpatients N=92 children from Detailed clinical Positive for 50/92 (33 No N° of persistent Rates 37% (18/47) vs In Bangladesh, where
GM, 2011 control h 15 days to 60 mo of history and Cryptosp. vs cases) - 3 diarrhea* (Cases 0% (0/39) cryptosporidiosis is
study age with diarrhea (46 laboratory Negative for weeks vs controls) endemic, it is
controls with investigations Cryptosp. Antibody (IgG) Median 68 [28; 110] vs associated with
negative stool levels to [25th-75th 4 [0; 10] persistent diarrhea.
coltures for Cryptosporidium percentiles] Although the dominant
Cryptosporidium; parvum gp15 antibody response
subsequently 7 (Initial-follow-up appears to be targeted
controls were found period) to conserved peptide
positive for PCR and Antibody (IgM) Median −29 [–97; 13] epitopes of g15,
were thus levels to [25th-75th vs 0 [–; 0] antibody responses to
considered cases) Cryptosporidium percentiles] polymorphic, species-
parvum gp15 or subtype specific
(Initial-follow-up epitopes may also
period) occur. These findings
Antibody (IgA) Median 83 [19; 243] vs have implications for

levels to [25th-75th 40 [3; 61] development of gp15 as
Cryptosporidium percentiles] a putative vaccine
parvum gp15 candidate*
(Initial-follow-up
period)
Antibody (IgG) Median 62 [19; 124] vs
levels to [25th-75th 0 [–7; 7]
Cryptosporidium percentiles]
hominis gp15
(Initial-follow-up
period)
Antibody (IgM) Median 2 [–20; 20] vs 0
levels to [25th-75th [–7; –8]
hominis gp15
(Initial-follow-up
period)
Antibody (IgA) Median 50 [10; 138] vs
levels to [25th-75th 4 [–1; 24]
hominis gp15
(Initial-follow-up
period)
AGE= acute gastroenteritis; PD= Persistent diarrhea; ProD= Prolonged diarrhea; QoS=Quality of Study.
Table 1.2.3. Chronic diseases and Immune deficits

Reference Study type Period of QoS Country In/Out Population Intervention Comparison FU ITT Outcomes RCT n Effect Effect size Comments
observation Patients n/N measures measure
Sugata K, Prospective Between +/- Japan Inpatients N= 62 Collection of HSCT — No Levels of RV — mean 0.22 ± 0.19 vs Although the duration
2012 cohort September pediatric recorded recipients vs antigenemia number ±SD 0.49 ± 0.18, P of antigenemia was
study 2004 and recipients at clinical data immunocomp = 0.0011 clearly longer in HSCT
February the time of and serum etent RV patients than in
2007 HSCT, weekly samples gastroenteritis immunocompetent RV
for 3 or 4 patients gastroenteritis patients,
months post HLA mismatch HLA matching OR (95%CI) 9.44 (1.09– the levels of viral
transplant vs matched 82.11) p=0.024 antigen were not as
high.
Pascarella F, Retrospectiv between +/- Italy Inpatients N= 193 Collection of IBD vs no IBD — No Positive C difficile — Rates 20 (24.7) vs 10 The present study has
2009 e, single- January 2005 patients aged recorded stool test results, n (8.9) p=0.004 demonstrated a higher
center, and 18 months to clinical data (%) prevalence of C difficile
observation December 18 years (81 and stool infection in a pediatric
al, 2007 affected by samples population with IBD
case-control IBD or with an compared with
study history of one without IBD.
diarrhea and
abdominal
pain and 112
controls) who
were admitted
Nylund CM, Retrospectiv Years 1997, + US Inpatients N= 10474454 Collection of Comorbidity vs — No Inflammatory — OR (95%CI) 11.42 (10.16- Clostridium difficile is
2011 e cohort 2000, 2003, children hospital no bowel disease 12.83) emerging as a major
study and 2006 hospitalized discharge comorbidity Solid organ 4.53 (3.92- agent of severe
(0.2% cases of data from transplant 5.24) diarrhea in children
clostridium national HIV infection 1.36 (1.04- with chronic conditions
infection) database 1.79)
Hematopoietic 3.31 (2.87-
stem cell 3.82)
transplantation
Neoplastic disease 3.10 (2.89-
3.31)
Fungal infection 2.71 (2.39-
3.07)
Cystic fibrosis 2.65 (2.22-
3.17)
Pancreatitis 2.86 (2.41-
3.39)
Hematologic 2.50 (2.34-
disorders 2.66)
Gastrostomy 2.00 (1.67-
2.39)
Liver disease 2.04 (1.80-
2.32)
Malnutrition 2.39 (2.14-

2.67)
Renal disease 2.09 (1.99-
Systemic lupus 2.19)
erythematosus 2.06 (1.58-
2.68)
Bandin F, Retrospectiv January 2006 - France Inpatients N=199 Collection of (1) infectious — No Etiologic group of — Rates Infectious Need to have a high
2009 e case series to December children who recorded diarrhea , (2) reported diarrheal 38/64 (59%), index of suspicion for
study 2008 received renal clinical data secondary to episodes (N=64) Immuno 14/64 cryptosporidiosis in
transplantatio and stool immunosuppr (22%), Not pediatric renal
n samples essant classified transplant patients who
treatment (3) 12/64 (19%) present with diarrhea.
unclassified Cryptosporidium in Rates 7/38 (18%) The routine stool
diarrhea. infectious diarrheal evaluations for
episodes parasites may not
identify
Cryptosporidium.
Henke- Retrospectiv 1 January + Germany Inpatients N=75 patients Collection of Comparing — Yes Immunosoppressio — OR (95%CI) 9.19 (2.86– Highly
Gendo C, e cohort 2005 to 30 of all ages recorded levels of NV n as a risk factor 29.47) immunosuppressed
2009 study June 2008 receiving high- clinical data excretions p<0.0001 patients as well as
level and stool Transplant OR (95%CI) 7.49 (2.06– young children fail to
immunosuppr samples recipient as a risk 28.32) p<0.001 eliminate NV infection
essive drug factor and shed the virus at
therapy with Age < 3yr as a risk OR (95%CI) 4.36 (1.23– high loads for a long
calcineurin factor 15.85) p<0.008 period of time.
inhibitors
Bok K, 2012 Review 2012 + High and Inpatients Immunocomp — — — — — — — — NVs are increasingly
low romised recognized as an
income patients (all important cause of
countries ages) with chronic gastroenteritis
persistent in
diarrhea immunocompromised
patients, as reflected by
the growing number of
clinical case reports
Kaiser P, Retrospectiv 1 October ++ Germany Inpatients 6884 children — — — — Underlying Cardiac — Number (%) 32 (1.5%) vs 89 The higher proportion
2012 e study 2002 to 31 < 5 years, disease(RV pos vs (3.2%), of cardiac patients in
May 2008 4880 RV RV neg) p<0.001 the RV− group is due to
positive and Underlying Number (%) 37 (1.7%) vs 79 multiple Clostridium
2118 RV Neurologic disease (2.9%), infections in the cardiac
negative. (RV pos vs RV neg) p=0.013 wards in Giessen,
Underlying Number (%) 21 (1%) vs 46 where 56 of the 62
Metabolic disease (1.7%), p=0.47 Clostridium infections
(RV pos vs RV neg) (partially mixed
infections) in the entire
study group were
observed (90.3%)
Bhutta ZA, Systematic + Low- Inpatients Hospitalized — — — — Increase of risf for Black, OR (95%CI) 4% with each It is not possible to
2008 review income and and not malnutrition at Lancet diarrheal determine the
countries Outpatien hospitalized 24mo of age with 2008 episode population-attributable
ts children ≤ 5 each diarrheal (cross- OR 1.04 (1.0– fraction
years of age episode sectional 1.08; p < 0.03) of stunting and
with diarrhea study in 3 undernutrition that
(Perù, Brasil, World may be related to PD
USA, region -
Bangladesh, Asia,
Haiti, England) Africa and
Latin
America)
— Lebenthal, Prolonged small
New York intestinal mucosa
Raven injuries has been
Press; named as a central
1984 mechanism in the
pathophysiology of PD,
but we must
discriminatebetween
persisting infective
colonization with
enteropathyand a
postinfective
enteropathy that fails
to heal or heals slowly
Mor SM, Prospective from + Uganda Inpatients N=243 Collection of Microsporidios 224/2 No Microsporidiosis in — OR (95%CI) 78.3 (30.8– microsporidian fungus
2009 cohort November children ≤ yr recorded is in children 43 children with 199.1) p < Enterocytozoonbieneus
study 2002 of age with clinical data with and concurrent 0.0001 i is associated with
through May Persistent and stool without cryptosporidiosis lower rates of weight
2003 diarrhea samples concurrent Microsporidiosis in OR (95%CI) 41.8 (18.3– gainin children in
cryptosporidio children with 95.4) p<0.001 Uganda with persistent
sis and HIV concurrent HIV diarrhea. This
Microsporidiosis in OR (95%CI) 153.0 (43.1– relationshipremained
children with 543.5) p<0.001 after controlling for HIV
concurrent HIV and concurrent
and cryptosporidiosis.
cryptosporidiosis
Microsporidiosis in OR (95%CI) 2.1 (1.2–3.7)
wasted children p= 0.013
Microsporidiosis in OR (95%CI) 1.2 (0.7–
underweight 2.2)p= 0.525
children
Microsporidiosis in OR (95%CI) 1.2 (0.7–
stunted children 2.2)p= 0.508
Idris NS, 2010 Prospective April 2008 to + Indonesia Inpatients N=42 children Collection of Comparing 38/42 Yes Immunocompromi — Rates HIV 16/42 The prevalence of
cross- February aged 6mo.-18 recorded rates of sed state and (42%); intestinal parasitic
sectional 2009 yrs , with clinical data intestinal presence of Malignancy infection among
study persistent and stool parasites parasites infection 4/42 (9%); immunocompromised
and/or samples infections Severe children with persistent
recurrent between malnutrition and/or recurrent
diarrhea and groups (NO HIV) 3/42 diarrhea was
had at least (7%); moderately high. The
one of the Immunosuppr main groups affected
following essive therapy were toddlers and
conditions: 1/42 (2%) preschoolers as well as
HIV infection, those children infected
malignancy, with HIV who were not
severe on antiretroviral
malnutrition, therapy or with low
on CD4 counts.
immunosuppr
essive therapy
for a minimum
of four weeks,
or primary
immunodefici
ency.
Umamahesw Case-control 17 mo, + India Inpatients N=120 Detailed Persistent vs 55/12 YES Children with PD — Rates 43/60 (72.2%) Protein energy
ari B, 2010 study November children from clinical acute diarrhea 0-3 and prior antibiotic OR (95%CI) 5.28 (2.01– malnutrition, vitamin A
2000-April 1 mo. to 10 yr. history and mont use 13.74) p = deficiency and prior
2002 of age with laboratory hs 0.0003 antibiotic use were the
persistent or investigation Children with PD Rates 8/60 (13.3%) risk factors for PD.*
acute diarrhea s and steroid use OR (95%CI) 4.46 (0.82-
31.9) p = 0.048
Children with PD Rates 48/60 (80%)
and anemia OR (95%CI) 3.74 (1.55-
9.15) p = 0.002
Children with PD Rates 24/60 (40%)
and vitamin A OR (95%CI) 4.28 (1.29–
deficiency 14.09) p =
0.012
Children with PD Rates 35/60 (58.3%)
and Z-score WFH OR (95%CI) 1.66 (1.0–2.77)
<-2 p = 0.04
Al Jarousha Case-control February + Palestine Inpatients N= 465 Detailed Diarrhea vs — Yes Risk for PD in OR (95%CI) 8.57 (3.98– Malnutrition is a risk
AM, 2011 study 2006-January children aged clinical not diarrhea malnourished 18.44)p <0.001 factor for PD
2007 up to 12 yrs history and children
(165 controls) laboratory
investigation
s
Das SK, 2012 Case-control 1991-2010 ++ Banglades Inpatients N= 3776 Detailed Persistent vs — Yes Children with PD — OR (95%CI) (36/294) OR Malnutrition remains a
study h children < 5yr clinical acute diarrhea who had wasting 1.62 (1.18, risk factor for PD
of age with PD history and syndrome 2.21) p<0.01
(944) and AD laboratory
(2832) investigation
s
Sutra S, 2012 Cross- 2011 + Thailand Inpatients Children < 5yr The authors — — Yes Persistent diarrhea — N° of 202 episodes age, sepsis, anemia,
sectional of age investigated episodes (1.6 per 1,000 chronic diseases,
study the number and rates admissions) malnutrition and HIV
of OPD visits Risk factors related Multivariate age, sepsis, are related to
(756,552; to PD analysis anemia, persistent diarrhea
1:5 ), IPD chronic
(124,403 diseases,
admissions; malnutrition
1:30) and HIV.
Manger MS, Prospective February + India Outpatien N=2296 Detailed — 2296/ Yes Risk for PD in — OR (95%CI) 1.77 (1.14, Poor folate status was
2011 cohort 1998- ts children 6-30 clinical 2296 children with 2.75) p = 0.01 an independent
study September mo of age history and folate plasma predictor of persistent
2000 laboratory concentrations < diarrhea in this
investigation 25th percentile population
s
HSCT=haemopoietic stem cell transplantation; IBD=Inflammatory bowel disease; NV= Norovirus; PD=Persistent diarrhea; QoS=Quality of Study;
RV=Rotavirus.
Table 1.3. Is there a relationship between the child’s clinical conditions and risk of severe or persistent diarrhea?
Reference Study type Period of QoS Country In/Out Population Randomization Intervention Comparison FU n/N ITT Outcomes Effect Effect size Comments
observation Patients measures measure (95% CI)
Verrotti A, Systematic 1993-2007 + Japan, Inpatients N=368 _ _ _ _ _ Incidence of Rates (%) 2.1–6.4% Benign afebrile
2009 Review UK, children <5 yr afebrile seizures, not related
Taiwan of age with seizures to severe
mild RV following RV dehydration or
gastroenteriti gastroenteritis electrolyte
s imbalance, have
been associated with
RV gastroenteritis
Chan CM, Retrospecti + Hong- Inpatients N=405 _ _ RV vs NV _ _ Maximun Mean ± SD 38.56 ± 1.01 Children with RV
2011 ve study Kong children infection body vs 37.65 ± infection had higher
between temperature 0.78; temperature and
1mo. and 6yr (RV vs NV) p<0.001 more diarrhea
of age with Presence of Rates (%) 96% vs 84%; episodes, while more
acute diarrhea p<0.001 blood-stained stools
gastroenteriti Presence of Rates (%) 1% vs and afebrile seizures
s (232 with RV bloody 5%;p=0.035 were noted in the NV
infection and diarrhea group
173 with NV C-reactive Mean ± SD 11.04 ±
infection) protein mg/L 18.18 vs
8.83 ±
16.96; p=
0.002
Sodium Mean ± SD 138.31 ±
mmol/L 3.20 vs
139.38 ±
2.92;
p<0.001
Length of stay Mean ± SD 3.89 ± 1.83
(days) vs 3.60 ±
1.67;
p=0.049
Presence of Rates (%) 1% vs 9%;
afebrile p<0.001
seizure
Fasheh Case-series _ Isolation of RV Number (%) 11/28 (39) Afebrile convulsion
Youssef W, during mild
2011 gastroenteritis is a
Isolation of 1/28 (4)
banal symptom with
Salmonella
good prognosis
Day TG, Case-series _ _ _ _ First reported cluster

2012 of children
presenting with
neurological
symptoms and stool
virology positive for
RV
Shai S, 2013 Surveillanc Between Cases of Number 26/84 Although the
e system April 2009 severe incidence is relatively
and March hypernatremi low compared
2011 a (>155mEq/L) with all RV cases,
between significant RV
community- morbidity could be
acquired identified
gastroenteritis
Cases of 10/84
severe
hyponatremia
(<125mEq/L)
between
community-
acquired
gastroenteritis
Cases of 58/84
encephalopat
hy between
community-
acquired
gastroenteritis
Cases of 3/84
deaths
between
community-
acquired
gastroenteritis
Shkalim V, Retrospecti — +/- Israel Inpatients 17 otherwise — — Cases were — — Toxic frequency 4(24%) vs Toxic appearence
2012 ve healthy compared to appearence (%) 1(6%), and convulsions on
comparativ children aged 17 age- (cases vs p=0.002 admission were
e study 2-36 months matched controls) more common
with non- children with Convulsions frequency 3(19%) vs 0, among children with
typhoid non-typhoid (cases vs (%) p=0.002 non-typhoid
Salmonella salmonella controls) Salmonella and
and gastroenteriti bacteremia if
bacteremia s compared to those
with Salmonella AGE.
Payne DC, Surveillanc January 1, + USA Inpatients, 516 children — — RV positive — — Frequency of frequency 95% vs 79%, Children with RV
2008 e system 2006 to June ED patients (181 and RV vomiting (RV p<0.001 infection presented
30, 2006 and inpatients, negative pos vs RV neg) more frequently with
outpatients 201 ED and patients Fever (RV pos frequency 78% vs 63%, vomiting, fever and
134 vs RV neg) p=0.001 lethargy compared
outpatients). Lethargy (RV frequency 53% vs 27%, to children with non

44% with RV pos vs RV neg) p<0.001 RV infection.
diarrhea.
Kaiser P, Retrospecti 1 October +/- Germany Inpatients 6884 children — — — — — Respiratory Number (%) 648 (30.6%) Hypernatremia is a
2012 ve study 2002 to 3 < 5 years, Infections vs 1,112 specifc complication
May 2008 4880 RV Rate (RV pos (40.2%), of RV positive AGE
positive and vs RV neg) p<0.001
2118 RV Abdominal Number (%) 23 (1.1%) vs
negative. symptoms (RV 118 (4.2%),
pos vs RV neg) p<0.001
Neurological Number (%) 50 (2.4%) vs
symptoms (RV 138 (5%),
Metabolic Number (%) 85 (4%) vs
disorders (RV 56 (2%),
Hypertonic Number (%) 49 (2.3%) vs
dehydration 15 (0.5%),
p<0.001
Ansaldi F, Prospective April 2005– +/- Italy Outpatients 3611 children — — RV positive — — Fever (RV pos frequency 56.2% vs Children with RV
2008 Cohort April 2006 < 5 years and RV vs RV neg) 31.8%, infection had
study surveyed by negative p<0.01 significantly more
10 primary patients Dehydration frequency 18.7% vs fever and
pediatricians; (RV pos vs RV 9.7%, dehydration than RV
684 with AGE neg) p<0.01 negative patients. No
Risk of RV AGE OR(95% CI) 2.6 (1.8- difference in number
in patients 3.7), p<0.01 of stools, blood in
with fever stools andabdominal
Risk of RV AGE OR(95% CI) 1.8 (1.1-3), pain.
in patients p=0.02
with
dehydration
Chisti MJ, Prospective September- +/- Banglade Inpatients 258 children — — Children who — — Absent OR(95% CI) 10.9 (2.1- the absence of
2011 Cohort December sh <5yr of age died vs peripheral 56.8), p < peripheral pulses
study 2007 admitted for children who pulse even 0.01 even after full
severe survived after rehydration, severe
diarrhea complete malnutrition,
rehydration hypoxaemia, lobar
Severe OR(95% CI) 7.9 (1.8- pneumonia and
malnutrition 34.8), p < hypernatraemia are
0.01 independent
Hypoxaemia OR(95% CI) 8.5 (1.0- predictors of death
75.0), p =
0.05
Radiological OR(95% CI) 17.8 (3.7-
lobar 84.5), p <
pneumonia 0.01
Hypernatraem OR(95% CI) 15.8 (3.0-
ia 81.8), p <
0.01
AGE=Acute gastroenteritis; NV= Norovirus; OR=odds ratio; QoS=Quality of Study; RV=Rotavirus.
1.4. Is there a relationship between setting or socio-economic factors and risk of severe or persistent diarrhea?
Table 1.4.1. Hospitalization
Reference Study type Period of Qo Country In/Out Population Randomization Intervention Comparison FU ITT Outcomes RCT n Effect Effect size Comments
observation S Patients n/N measures measure (95% CI)
Waisbourd- Prospective Between +/- Israel Inpatients N= 2287 — Weekly Community — — Percentage of — Correlation P <.0001 Nosocomial
Zinman O, Cohort study 2003 and children RV surveillance acquired vs nosocomial RV cases can be
2011 2006 AGE (1931 of the nosocomial AGE in children easily
community microbiologic treated in full prevented by
acquired 356 laboratory for compliance with adherence to
Nosocomial) hospitalized hand hygiene hand hygiene
children measures
with positive
fecal RV
antigen
Waisbourd- Prospective From +/- Israel Inpatients N=356 children — Collection of — — — Children with — Number (%) 320/356 The risk of
Zinman O, Cohort study January 1, with clinical data Nosocomial-RV (90%) nosocomial
2009 2003 to Nosocomial-RV AGE ≤ 2 years diarrhea is
December AGE related to
31, young age
2006
Wildi- Retrospective January +/- Switzerland Inpatients N=590 children — — Community — — Persistent — OR (95%CI) 1.3 (0.6– Nosocomial
Runge S, cohort study 2002 to <3yr of age acquired vs Diarrhea 3.0), p=0.46 cases tended
2009 March 2006 hospitalized Nosocomial (>5days) to be less
for RV acute diarrhea Community severe than
gastroenteritis (23.6%) vs those acquired
Nosocomial in the
(18%) community
Vomiting events OR (95%CI) 5.3 (2.6–
(>2/day) 10.8), p<
Community 0.001
(78%) vs
Nosocomial
(35%)
Dehydration OR (95%CI) 11.3 (5.7–
(>5% of weight 22.4), p
loss) Community <0.001
(85%) vs
Nosocomial
(35%)
Wiegering Retrospective April 1, + Germany Inpatients 650 charts of — — Community — — Gastroenteritis — mean 1.5±0.2 vs The underlying
V, 2011 cohort study 2005 to children with acquired vs score number ±SD 3.6±0.3, disease which
May 31, AGE. 262 Nosocomial (Community p<0.001 led to
2008 (43.8%) had diarrhea acquired vs admission,
RV, 188 Nosocomial predominantly
(31.4%) NV, 58 infections): airway
(9.7%) pulmonary infections,
Adenovirus, symptoms explains the
47(7.9%) Gastroenteritis mean 13±0.1 vs high
Salmonella. score number ±SD 9.8±0.2 , respiratory
(Community p<0.001 symptoms
acquired vs score
Nosocomial
infections):
gastrointestinal
symptoms
Garcia- Cross- 2003-2008 + Spain Inpatients N=3265 — — Community — — Nosocomial RV- — Rates (%) 892/3265 Children under
Basteiro sectional children < 5 acquired vs AGE (27%) 12 months old
AL, 2011 study years of age Nosocomial Annual incidence Mean 2.5 cases per appear to be at
admitted for diarrhea of Incidence 1,000 (2.0 to higher
RV-AGE presumed rate (95%CI) 2.8) risk of
nosocomial RV- acquiring
AGE per 1000 nosocomial RV
hospitalizations gastroenteritis
Age of Mean ±SD 5.08±9.4 vs than older
hospitalized 7.6±10.1 children
children with
RV-AGE
(nosocomial vs
community
acquired) (mo)
Gleizes O, Review — + France, Inpatients Children with a — — Community — — Nosocomial/ — Ratio France:
2006 Germany, diagnosis of acquired vs Community 0.61 ;
Italy, Nosocomial Nosocomial acquired RV in Germany
Poland, RV-AGE diarrhea children <5yr of 1.04; Poland:
Spain and age 0.64; Spain:
the United 0.96; UK:
Kingdom 0.76
Asymptomatic Rates (%) 18-39%
manifestations of
Nosocomial RV
infection in
children <3mo of
age
RV-infected Rates (%) 76–78% The main

health-care vectors of
workers taking transmission
care of children are
with community- contaminated
acquired RV-AGE (mostly
uninfected)
health care
workers
Duration of Mean France: +5d; The rate of NV
hospital stay difference Italy: +1.7d; infection can
(days) Poland: +5.9; rise to 70% if
Nosocomial vs Spain: +1.8; patients stay
Community- UK +4 hospitalized
acquired AGE for 6 days
Age of Rates (%) 48% vs 20%
hospitalized
children with
RV-AGE
(nosocomial vs
community
acquired) (0-5
mo)
hospitalized
children with
RV-AGE
(nosocomial vs
community
acquired) (6-11
mo)
hospitalized
children with
RV-AGE
(nosocomial vs
community
acquired) (12-23
mo)
hospitalized
children with
RV-AGE
(nosocomial vs
community
acquired) (24-59
mo)
Nosocomial Rates (%) 2 and 13%

diarrhea
requiring
rehospitalization
Ogilvie I, Scoping — — Western Inpatients 76 studies — — Community — — Patients with 2 (n=3734; Rates (%) 42.6% RV
2012 review Europe from 16 acquired vs severe n=251) gastroenteritis
countries on Nosocomial nosocomial is a common
European diarrhea RVGE in France, disease
children <5 yr Italy, Spain and associated
of age with the UK with significant
community- Patients with Rates (%) 24.4%, morbidity and
acquired and severe 30.2% and costs
nosocomial nosocomial 40% across Western
diarrhea RVGE in Austria, Europe
Germany, and
Switzerland
Severe 2 (Ireland Rates (%) 80% vs 55%
dehydration in n=663; (Ireland)
children with Sweden 10.8% vs
community- n=984) 0.8%
acquired vs (Sweden)
nosocomial
gastroenteritis
Mortality due to 1(n=10,99 Incidence 0.74 per
nosocomial 0) rates 100,000 vs
RVGE (< vs > 0.16 per
12mo) 100,000
AGE= acute gastroenteritis; NV= Norovirus; OR=odds ratio; QoS=Quality of Study; RV=Rotavirus; RVGE= Rotavirus gastroenteritis.
Table 1.4.2. Socioeconomic factors
Reference Study type Period of QoS Country In/OutPatients Population Randomization Intervention Comparison FU ITT Outcomes Effect Effect size Comments
observation n/N measures measure (95% CI)
Pockett Retrospective 1st April 2009 +/- UK Inpatients N=1334 children — — Correlation — — Variation of Rates from 0.346 Hospital admissions
RD, 2011 cohort study and 31st ≤5 yr of age with with hospital to 0.287 per increased as deprivation
March 2010 RV-AGE deprivation admissions' rates in 10,000 (p < increased*
rank relation to the 0.001)
decrease of a
deprivation ranking
*Index of Multiple Deprivation (IMD) 2007 for England
Kyle RG, Retrospective — + UK Inpatients (ED) 24,481 children — — — — — Index of Multiple Sperman 0.31, p=0.09 There were no
2011 study under 15 years Deprivation rho statistically significant
admitted to ED for overcrowding Sperman 0.21, relationships between
breathing rho p=0.267 the ED admission rate of
difficulty, fever or houses in poor Sperman 0.11, children admitted for
diarrhoea during condition rho p=0.543 diarrhoea and the Index
2007/2008. air quality Sperman 0.16, multiple derivation and
rho p=0.387 its single indicators.
homelessness Sperman 0.14,
rho p=0.439
AGE= acute gastroenteritis; ED=emergency department; QoS=Quality of Study; RV=Rotavirus.
Table 1.4.3. Day care attendance
Reference Study Period of QoS Country In/Out Population Randomization Intervention Comparison FU n/N ITT Outcomes measures RCT Effect Effect size Comments
type observation Patients n measure
Sandora TJ, RCT — + USA Outpatients N= 292 Computered Supply of Controls 281/292 Yes Gastrointestinal- — IRR 0.41 (0.19–0.90) This intervention
2005 families with permuted-blocks alcohol-based Illness transmission (95% CI) p=.03 significantly
children aged design with hand sanitizer (treated vs controls) reduced the
< 5yr random block to use at home transmission of
sizes GI illnesses in the
homes of families
with children
who were
enrolled in out-
of-home child
care.
Kotch JB, RCT September + USA Outpatients N=388 infants Appropriate Installation of Controls 388/388 No Child Diarrhea — Incident 0.90 vs 1.58 High-quality
2007 2002 to and toddlers diaper- Frequency per 100 rates (p<0.001) equipment is
January attending changing, Child-Days (treated associated with
2003 child-care hand-washing, vs controls) significantly
centers (23 and food- % of Days Child Ill per Incident 4.0 vs 5.0 fewer episodes
matched- preparation 100 Child-Days rates (p<0.001) of diarrhea
paired centers) equipment (treated vs controls) among children
% of Days Caregiver Incident 0.77 vs 1.73 and fewer sick
Absent because of rates (p<0.001) days among staff.
Illness (treated vs
controls)
Grimprel E, Surveil December + France Outpatients N=371 children — — — — No Cases of RVGE per — Incidence 46.7 (26.7-75.8) RV can easily
2010 lance 2006 and aged <3yr 100,000 person-days rate spread in a day
study May 2007 attending (95%CI) care setting
child-care Age-distribution of Rates (%) 0-11 mo: 50%; 12-
centers children with RV- 23mo: 37%;
AGE >24mo: 13%
AGE= Acute gastroenteritis; GI=Gastrointestinal; QoS=Quality of Study; RV=Rotavirus; RVGE=Rotavirus gastroenteritis.
CLINICAL EVALUATION AND DISEASE SEVERITY
Table 2.1. What are the indications for a medical visit?
Reference Study type Period of QoS Country In/Out Population Randomization Intervention Comparison FU ITT Outcomes measures GL Effect Effect Comments
observation Patients n/N n measure size
(95% CI)
Williams Retrospective May 1, 2004 + US Outpatients N= 19731 — Vanderbilt Postlicensure — — AGE-related Call — IRR (95% CI) 0.72 A telephone
DJ, 2012 surveillance to April 30, AGE- Telephone Triage period (2007– Proportions After RV (0.67– consultation
system 2007 related Program 2010)) vs Vaccine Licensure (RV 0.78) can be
May 1, 2007 calls Prevaccine Season) appropriate in
to April 30, period (2004– the
2010 2007 management
of
uncomplicated
cases of AGE
van den Systematic 2011 ++ Europe, Outpatients N=8 — Assess the quality — — — Indication to medical n=4 Consensus (n/N) 3/4; Y Not
Berg J, review USA, guidelines of international visit: Young age and Consistency recommended
2011 Canada CPG for the (Y/N) of the by ESPGHAN,
management of recommendation to be included*
acute diarrhea in Indication to medical Consensus (n/N) 4/4; Y
children in high visit: High Output --> 6 and Consistency
income countries diarrheal stool in 24 h, (Y/N) of the
with the Appraisal or > 3 vomits in 24 h or recommendation
of Guidelines, watery diarrhea > 6
Research and times a day > 3 days (<2
Evaluation years: > 1 day)
(AGREE) Indication to medical Consensus (n/N) 3/4; Y
instrument visit: Persistent and Consistency
vomiting or >2 (Y/N) of the
vomits/24h recommendation
Indication to medical Consensus (n/N) 3/4; Y*
visit: Reported signs of and Consistency
severe dehydration* (Y/N) of the
recommendation
Indication to medical Consensus (n/N) 4/4; Y
visit: Signs of severe and Consistency
cause for (Y/N) of the
diarrhea/underlying recommendation
disease
*Consistency of recommendations: If more than 50% of these guidelines made an identical recommendation, it was considered consistent
AGE= acute gastroenteritis; CPG=Clinical practice guidelines; ESPGHAN= European Society for Paediatric Gastroenterology, Hepatology, and Nutrition;
QoS=Quality of Study; RV=Rotavirus.
2.2. Is there any clinical feature that may suggest a bacterial versus viral etiology of diarrhea?
Table 2.2.1. Bacterial versus viral
Reference Study type QoS Country In/Out Population Randomization Intervention Comparison FU ITT Outcomes Effect Effect size (95% CI) Comments
Patients measures measure
Wiegering V, Retrospective + Germany Inpatients 650 charts of _ _ Comparisons _ _ Respiratory mean 1.8±0.1 vs 0.6±0.3, p<0.001 Children with viral infection
2011 cohort study children with AGE between all symptoms score score (0- had significantly more
reviewed viral (all viral vs 6)±SD respiratory associated
between 2005 infections and Salmonella) symptoms and vomiting, but
and 2008. 262 Salmonella Duration of mean 3.4±0.1 vs 6.1±0.4, p<0.001 less episodes of diarrhea
(43.8%) had RV, infection diarrhea (all viral number and total duration of
188 (31.4%) NV, vs Salmonella) ±SD diarrhea when compared to
58 (9.7%) Diarrhea events mean 3.8±0.1 vs 10.4±0.5, children with Salmonella
Adenovirus, (all viral vs number p<0.001 infection.
47(7.9%) Salmonella) ±SD
Salmonella. Vomiting events mean 2.6±0.2 vs 1±0.4, p<0.001
(all viral vs number
Samonella) ±SD
Comparisons _ _ Duration of mean 4.1±0.2 vs 2.7±0.2 vs Children with RV infection
between viral diarrhea (RV vs number 3.4±0.3, p<0.001 had significantly higher
infections: RV NV vs AV) ±SD severity scores, more
vs NV vs Diarrhea events mean 4.4±0.2 vs 3.2±0.2 vs diarrheal events and long-
Adenovirus (RV vs NV vs AV) number 3.4±0.4, p<0.001 lasting diarrhea. In contrast
±SD NV infection had more
Vomiting events mean 2.4±0.2 vs 3.2±0.2 vs vomiting events.
(RV vs NV vs AV) number 1.6±0.3, p=0.05
±SD
Gastroenteritis mean 13.5±0.2 vs 11.9±0.2 vs
score (RV vs NV score (0- 11.5±0.4, p<0.001
vs AV) 15)±SD
Payne DC, Surveillance + USA Inpatients, 516 children (181 _ _ RV positive _ _ Fever (RV pos vs frequency 78% vs 63%, p=0.001 Children with RV infection
2008 system ED patients inpatients, 201 ED and RV RV neg) presented more frequently
and and 134 negative Lethargy (RV pos frequency 53% vs 27%, p<0.001 with vomiting, fever and
outpatients outpatients). 44% patients vs RV neg) lethargy compared to
with RV diarrhea. children with non RV
infection.
Narkeviciute Retrospective +/- Lithuania Inpatients Random Random _ RV vs NV _ _ High grade fever frequency 81% vs 48%, p<0.0001 RV infection presents more
I, 2008 study retrospective selection of infection (BT> 38°C) (RV vs likely with fever, usually
selection of 140 charts; no NV) high grade (>38°) and
charts of children allocation to Frequency of frequency 97% vs 66%, p<0.0001 frequent diarrheal episodes
< 3y with NV (70) any fever (RV vs NV) (>7/d). NV AGE is commonly
and RV (70) intervention Diarrhea >7 frequency 42% vs 12%, p<0.0001 characterized by the
infection. episodes/d (RV presence of vomiting (71%
vs NV) more than 4episodes/d) and
Vomiting > 4/d frequency 49% vs 71%, p=0.01 in 1/5 of cases without
(RV vs NV) diarrhea
Children without frequency 4% vs 19%, p=0.01

diarrhea (RV vs
NV)
Ansaldi F, Prospective +/- Italy Outpatients 3611 children < 5 _ _ RV positive _ _ Fever (RV pos vs frequency 56.2% vs 31.8%, p<0.01 Children with RV infection
2008 Cohort study years surveyed by and RV RV neg) had significantly more fever
10 primary negative Dehydration (RV frequency 18.7% vs 9.7%, p<0.01 and dehydration than RV
pediatricians; 684 patients pos vs RV neg) negative patients. No
with AGE Risk of RV AGE in OR(95% 2.6 (1.8-3.7), p<0.01 difference in number of
patients with CI) stools, blood in stools and
fever abdominal pain.
Risk of RV AGE in OR(95% 1.8 (1.1-3), p=0.02
patients with CI)
dehydration
Ghorashi Z, Case-control +/- Iran Inpatients 49 cases with _ _ _ _ _ Frequency of frequency 8 vs 2, p=0.014 The frequency of Shigellosis
2010 study convulsion due to Shigellosis (cases in the case group was
AGE (in absence vs controls) significantly higher than in
of electrolyte the control group.
imbalance) and 51
controls with AGE
but without
convulsions
Chen SM, Prospective + Taiwan Inpatients 168 children (1.2 - _ _ _ _ _ Maximum Median RV 6(4-9.5) vs NV 4 (3-6.25) Children with Salmonellosis
2012 Cohort study 4.7 years) number of (IQR) vs SA 8(6-10), p<0.001 demonstrated higher fever,
admitted for AGE. diarrheal bloody diarrhea and more
30 with RV, 25 episodes/d (RV vs diarrheal episodes when
NV, 26 Salmonella NV vs SA) compared to RV and NV
(SA). Maxiumun Median RV 4 (2-7) vs NV 2.5 (1-5.2) positive patients.
number of (IQR) vs SA 1 (1-2), p<0.001
vomiting
episodes/d (RV vs
NV vs SA)
Fever > 38°C (RV Frequency RV 36 (87.8%) vs NV 13
vs NV vs SA) (%) (38.2%) vs SA 29 (100%),
p<0.001
Maximun body Median RV 38.8 (38.4 -39) vs NV
temperature (RV (IQR) 37.9 (37.2-38.7) vs SA 39.1
vs NV vs SA) (38.9-39.6), p<0.001
Stool occult blood Frequency RV 16 (39%) vs NV 8
(%) (23.5%) vs SA 18 (62.1%),
p<0.001
Kaiser P, Retrospective Germany Inpatients 6884 children < 5 _ _ _ _ _ Respiratory Number 648 (30.6%) vs 1,112 Hypernatremia is a specific
2012 study years, 4880 RV Infections Rate (%) (40.2%), p<0.001 complication of RV positive
positive and 2118 (RV pos vs RV AGE
RV negative. neg)
Abdominal Number 23 (1.1%) vs 118 (4.2%),
symptoms (RV (%) p<0.001
pos vs RV neg)
Neurological Number 50 (2.4%) vs 138 (5%),
symptoms (RV (%) p<0.001
pos vs RV neg)
Metabolic Number 85 (4%) vs 56 (2%), p<0.001

disorders (RV pos (%)
vs RV neg)
Hypertonic Number 49 (2.3%) vs 15 (0.5%),
dehydration (%) p<0.001
AGE= acute gastroenteritis; NV=Norovirus; QoS=Quality of Study; RV=Rotavirus.
Table 2.2.2. Systemic Involvement
Reference Study type Qo Country In/Out Population Randomization Intervention Comparison F ITT Outcomes Effect Effect size Comments
S Patients U measures measure (95% CI)
Shkalim V, Retrospective +/- Israel Inpatients 17 otherwise healthy _ _ Cases were compared to _ _ Toxic frequency 4(24%) vs Toxic appearence and convulsions
2012 comparative children aged 2-36 17 age-matched children appearence (%) 1(6%), on admission were more common
study months with non- with non-typhoid (cases vs p=0.002 among children with non-typhoid
typhoid Salmonella salmonella gastroenteritis controls) Salmonella and bacteremia if
and bacteremia Convulsions frequency 3(19%) vs compared to those with
(cases vs (%) 0, p=0.002 Salmonella AGE.
controls)
AGE=acute gastroenteritis; QoS=Quality of Study.
2.3 How is dehydration assessed?
Table 2.3.1. Clinical dehydration scale
Reference Study design Country Aim Setting N Age range Inclusion Outcome measures Results/conclusions
criteria
Friedman Prospective Canada To develop a clinical ED 137 1-36 mo (median: 18 GE Urine output; general appearance; ‘Clinicians and researchers may consider this four-
JN, 2004 cohort study dehydration scale for use in mo) eyes; mucous membranes (tongue); item, 8-point rating scale, developed using formal
children <3 y of age. tears; respiratory rates; heart rate. measurement methodology, as an alternative to
scales developed ad hoc.’
Goldman Prospective Canada To validate the CDS with a new Tertiary 205 1 mo -5 y (22.4 ± Symptoms of Length of stay, proportion of The CDS was valuable in predicting a longer length
RD, 2008 cohort study cohort of patients with AGE. care ED 14.9 mo) AGE children receiving intravenous of stay and the need for intravenous rehydration
rehydration; proportion of children in children with symptoms of AGE.
with abnormal serum pH values or
bicarbonate levels.
Bailey B, Prospective Canada To validate the CDS for Tertiary 150 1 mo – 5 y Vomiting Primary: the association between The CDS is a good predictor of (1) length of stay in
2010 cohort study children with gastroenteritis in care ED and/or diarrhea the CDS for children and the length the ED after being seen by a physician; (2)
a different ED from where it of stay in ED after being seen by the perceived need for IV rehydration; (3) utilization of
was initially derived and attending physician. laboratory blood tests.
validated.
Gravel J, Prospective Switzerland, To validate the association ED 219 1 mo -5 y (mean age: Vomiting Primary: the percentage of ‘CDS categories correlate well with markers of
2010 cohort study Canada between the CDS and markers 22 ± 14 mo; and/or diarrhea dehydration calculated by the dehydration four young children complaining of
of dehydration in children aged range 4 mo to 4 y) difference in weight at first vomiting and/or diarrhea in the ED.’
1 mo to 5 y visiting ED for evaluation and after recovery.
vomiting and/or diarrhea.
Secondary: proportion of blood test
measurements, intravenous use,
hospitalization, and inter-rater
agreement.
Kinlin LM, Prospective Canada To evaluate the reliability and Tertiary 226 ≥3 mo GE and Reliablity (by comparing the scores ‘In children administered intravenous rehydration,
2012 cohort study validity of the CDS in a cohort ED dehydration assigned independently by a trained the CDS was characterized by moderate
of children with gastroenteritis requiring research nurse and a physician). interobserver reliability and weak associations
and evidence of dehydration. intravenous Validity (by using parameters with objective measures of disease severity. These
rehydration reflective of disease severity: weight data do not support its use as a tool to dictate the
gain; baseline laboratory results; need for intravenous rehydration or to predict
willingness of the physician to clinical course.’
discharge the patient;
hospitalization; length of stay).
Pringle K, Prospective Rwanda To determine whether the Hospital 49 <15 y (but analysis Diarrhea and/or Sensitivity; specificity. ‘In this sample of children, the WHO scale,
2011 cohort study WHO scale, the Gorelick scale limited to children vomiting Gorelick scale, and CDS did not provide an
and the CDS scales can fitting within the accurate assessment of dehydration status when
accurately assess dehydration predefined age used by GP and nurses in a developing world
status in children when ranges for each of setting’.
performed by nurses or GP in a the scales)
low-income country.
Pruvost I, Prospective France To estimate the value of post- Tertiary 293 1 to 24 months of Acute diarrhea, Pearson correlation between post- The correlation between post-illness and
2013 cohort study illness weight gain ED age and daily illness and theoretical weight theoretical weight was excellent (0.978), but
prospectively as a gold weight bootstrapped linear regression analysis showed
standard for acute weight loss surveillance for that post-illness weight underestimated
in a larger population. 7 days following theoretical weight by 0.48 kg. These data suggest
the ED visit, that post-illness weight is of little value as a gold
were included standard to determine the true level of
dehydration
CDS=clinical dehydration scale; ED=emergency department; WHO=World Health Organization.
Table 2.3.2. Severity scores
Reference Study design Country Aim Setting N Age range Inclusion criteria Outcome measures Results/conclusions
Schnadower D, Prospective US To evaluate the reliability, construct ED 28 Between 91 days and 48 AGE Reliability, construct validity, ‘The Modified Vesikari Score effectively
2013 cohort study validity, and generalizability 2 months of age) and generalizability measures global severity of disease and
of the Modified Vesikari Score by of the Modified Vesikari performs similarly in varying
studying its characteristics in a Score populations within the US health care
network of pediatric system. Its characteristics support its
EDs in the United States use in multisite outpatient clinical
trials.’
Ruuska T, 1990 Prospective Finland To assess the use of the classical Hospita 33 24-32 months of age AGE Severity of symptoms Using this system, the mean severity
cohort study Vesikari score for clinical severity of l 6 between RV e non-RV AGE score for the 65 episodes of RV
diarrhoeal episodes diarrhoea was 11.0 +/- 3.7 as compared
to 5.6 +/- 3.2 for the 183 episodes of
non-RV diarrhoea (p<0.001).
AGE= acute gastroenteritis; ED=emergency department; RV=Rotavirus.
Table 2.3.3. Clinical and laboratory assessment

Reference Study design Country Aim Setting N Age Inclusion Outcome measures Results/conclusions
range criteria
Parkin PC, Data were Canada To evaluate clinical and laboratory ED 93 1-36 mo AGE For a clinical score of 0, the LR+ 2.2 Clinicians may find it useful to incorporate the Clinical
2010 collected assessment (serum bicarbonate (0.9-5.3); Dehydration Scale and laboratory measures into clinical
prospectively; and venous pH) of dehydration For a clinical score of 1 to 4, the LR+ decision-making algorithms to assess dehydration severity
however the severity in children. was 1.3 (0.90-1.74); in children with acute gastroenteritis.
analysis was For a clinical score of 5 to 8, the LR+
post hoc. was 5.2 (2.2-12.8);
For a venous pH <7.32, the LR+ was
7.2 (2.4-21.9);
For serum bicarbonate <18 mmol/L,
the LR+ was 11.6 (3.5-38.0).
AGE= acute gastroenteritis; ED=emergency department; LR=likelihood ratio.
Table 2.3.4. Standardized Scoring System
Roland D, 2010 Prospective Australia To determine if scoring system ED 100 1 mo-12 y GE Estimated percentage The clinical scoring system used did not
observational based on standardized clinical (median 24 mo) dehydration. Agreement reduce the variability of assessment of
study signs would reduce the variability between raters. dehydration
between doctors’ assessment of
dehydration.
ED=emergency department; GE=gastroenteritis.
Table 2.3.5. Ultrasound
Chen L, 2007 Prospective US To compare the IVC and Ao diameters ED 72 6 mo-16 y Subjects with IVC/Ao ratio The ratio of inferior vena cava diameter is lower
observational ratio of dehydrated children with evidence of in children with clinical dehydration. It increases
study controls and to compare the IVC/Ao ratio dehydration plus with administration of IV fluid boluses.
before and after IV rehydration in matched controls
children with dehydration.
Chen L, 2010 Prospective US To validate the use of bedside ultrasound ED 112 6 mo-18 y GE Sensitivity, specificity, IVC to Ao diameter was a marginally accurate
observational measurement of IVC/Ao diameter by likelihood ratios, area measurement of acute weight loss in children
study investigating whether IVC/Ao ratio under the receiver with dehydration from gastroenteritis
correlated with dehydration in children operator characteristic
with AGE. curves.
To investigate the inter-rater variability
of the IVC/Ao measurements.
Levine AC, Prospective Rwanda To determine the test characteristics for ED 73 1 mo-10 y Diarrhea and/or Sensitivity, specificity, Ao to IVC and IVC inspiratory collaps. Ultrasound
2010 cohort study two different ultrasound measures of vomiting likelihood ratios, area if the aorta/IVC ratio can be used to identify
severe dehydration in children (Ao to IVC) under the receiver severe dehydration in children presenting with
ratio and IVC inspiratory collapse and the operator characteristic acute diarrhea.
WHO dehydration scale. curves.
AGE= acute gastroenteritis; Ao=aorta; ED=emergency department. IVC=inferior vena cava; WHO=World Health Organization.
Table 2.3.6. Hand-held bladder ultrasound
Reference Study design Countr Aim Setting N Age range Inclusion criteria Outcome measures Results/conclusions
y
Enright K, 2010 Prospective UK To evaluate the utility of a hand-held Tertiary ED 45 4 mo – 10 y Possible Primary: the ability to document the Serial bladder ultrasound scanning using a
observationa bladder ultrasound scanner in dehydration hourly rate of urine production for hand-held device is a convenient non-
l study monitoring urine production in each child, using the hand-held invasive and objective adjunct in the
children attending the emergency bladder scanner. management of suspected dehydration in
department with suspected Secondary: the relationship between ED.
dehydration. the measured urine production and
clinical features of dehydration,
patient disposal and rehydration
therapy.
ED=emergency department;
Table 2.3.7. Digital videography to measure capillary refill time
Shavit I, Prospective Canada To determine whether digitally Tertiary 83 1 mo – 5 y Gastroenteritis judged to be at Sensitivity, specificity, Digitally measured capillary-refill time
2006 cohort study measured capillary-refill time assesses ED least mildly dehydrated. likelihood ratios, area more accurately predicts significant
the presence of significant dehydration under the receiver dehydration (≥5%) in young children with
(≥5%) in young children with GE more operator characteristic GE than overall clinical assessment.
accurately than conventional capillary curves.
refill and overall clinical assessment.
ED=emergency department; GE=gastroenteritis.
Table 2.3.8. Bioelectric impedance
Dunkelmann L, Case series Switzerland To compare a bioimpedance device to 26 0.5 to 10 y AGE The subgroup of children with mild Possible usefulness of bioelectric
2012 the validated clinical score for the dehydration (n=14) had significantly lower impedance for the assessment of
determination of the degree of Ω50 compared to the subgroup of children dehydration.
dehydration in children with AGE. with moderate/severe dehydration
(n=12), p=0.003.
AGE= acute gastroenteritis;
Table 2.3.9. Plasma water
Plaisier A, 2010 Prospective The To evaluate plasma water as a ED 101 Up to 12 y AGE and Plasma water did not There is insufficient evidence to justify
cohort study Netherland diagnostic tool in the assessment dehydration correlate with the the use of plasma water as a diagnostic
s of dehydration in children with percentage of weight loss. tool in the assessment of dehydration
AGE admitted to hospital with in children with AGE.
moderate to severe dehydration.
AGE=acute gastroenteritis; ED=emergency department; GE=gastroenteritis.
DIAGNOSTIC WORKUP
Table 3.1. Is There Any Reliable Hematological Marker of Bacterial Diarrhea?
Reference Type of Study Country Inpatient Follow- Population Intervention Comparison Outcome measures Results /Effect size Risk Source of Conclusions and Comments
Outpatient up n/N of Funding
Bias
Wiegering Retrospective Germany Inpatient Not 650/1157 NA Clinical score to Etiology Etiology: NA None RV was the commonest cause of
V, 2011 Apr 2005 to reported children with differentiate Duration of diarrhea 84.9% viral viral AGE and Salmonella the
May 2008 pathogen between Laboratory and 7.9% Salmonella commonest cause of bacterial
proven AGE different other hematologic 7.2% multiple agents AGE
Age etiologies markers Duration of diarrhea: Children with bacterial AGE were
22d-17.9y All viral 3.4±0.1 days older, had a more severe clinical
(mean 2.4y) Salmonella 6.1±0.4 days course, significantly longer
(p<0.001) duration and significantly more
CRP elevated inflammatory markers
Viral AGE 1.2±0.1 These parameters may make
Salmonella AGE 6.9±0.4 possible to differentiate between
(p<0.001) viral and bacterial AGE
ESR
Viral AGE 15±0.8
Salmonella AGE 27±2.2
(p<0.001)
Marcus N, Prospective Israel Outpatient 7-12 days 75 children NA Bacterial vs Validity and QR-CRP (mg/L), NA QR-CRP assay CRP levels of 95mg/L or more
2007 Convenient ER (med 2.4) AGE Viral AGE feasibility of QR-CRP mean±SD kit was within 48 hours of presentation
sample Age 4d - 17y in diagnosis of Bacterial 22.3.8±150.3 provided by had a high sensitivity and
Aug 2002 to 44 children bacterial vs viral Viral 30±50 Orion specificity for predicting culture-
Feb 2003 included AGE (P<0.001) DiagnosFinland confirmed bacterial AGE
Bacterial QR-CRP ≥ 24.5 mg/L
8/44 (18%) OR 1.49 (95%CI 1.13-1.90
Viral AGE PPV 70%, NPV 97%
36/44 (82%) QR-CRP ≥ 95 mg/L
OR 1.49 (95%CI 1.13-1.90
PPV 91.7%, NPV 87%
Chen SM, Prospective Taiwan Inpatients NA 168 children NA Bacterial vs Diagnostic RV vs Salmonella NA Chung Shan IL-10 exhibited a significant high
2012 March 2008 AGE Viral AGE performance ANC, mm3 Hospital level in the acute phase of RV
to Age 4m- 14y IL-6, IL-10, 8075 (4225-13407) vs (CSH 97A-03) and NV AGE in children and
Jan 2009 ANC, CRP 4444 (3118-5867) showed a significant
Pathogens RV vs P= 0.004 discriminating ability between
identified in NV CRP, mg/dl the two most common viral
123/168 0.62 (0.3-1.59) vs pathogens
82 viral AGE Viral vs bacterial 6.42 (3.06-12.25)
36 bacterial AGE P≤ 0.001
AGE IL-6, IL-10 (p<0.001)
IL-6, IL-10 RV vs NV
assayed: AUC±SE (95% CI)
55 viral AGE IL-6
26 Salmonel 0.663±0.075(0.515±0.81)
11 healthy P=0.039
controls IL-10
0.710±0.69 (0.574-0.84)
P= 0.008
Korczowski Prospective Poland Inpatients NA 129 children NA Different Performance of PCT PCT> 5ng/ml NA None declared In this study PCT was a more
B, 2004 diarrhea etiologies of compared to CRP 100% systemic infections reliable marker than CRP of
37 systemic diarrhea 61% bacterial AGE systemic bacterial infection in
infections 7% RV AGE children with diarrhea. PCT was
36 bacterial 23% IBD more specific but less sensitive in
AGE CRP> 2mg/dl the differentiation of bacterial
43 RV AGE 89% systemic infections and non-bacterial etiology of
13 IBD 61% bacterial AGE inflammation.
19% RV AGE
46% IBD
AGE= acute gastroenteritis; ANC=absolute neutrophil count; AUC=area under the curve; IL-6=interleukin 6; IL-10=interleukin 10; CI=confidence interval;
CRP=C-reactive protein; NPV=negative predictive value; NV=norovirus; OR=odds ratio; PCT=procalcitonin; PPV=positive predictive value; QR-CRP=quick-read
C-reactive protein; RV= rotavirus; SE=sensitivity; SP=specificity.
Table 3.2. Stool markers for identification of bacterial diarrhea
Referenc Type of Country Inpatient Follow- Population Intervention Comparison Outcome Results /Effect size Risk of Source of Conclusions and Comments
e Study Outpatient up n/N measures Bias Funding
Sykora J, Prospective Czech Inpatients NA 66 children NA BGA Reference fCP in fCP NA None fCP is a valuable, non-invasive and esily
2010 Republic and AGE vs healthy children BGA 219.9µg/g (119- declared measured laboratory test
Outpatient Age 1-36m VGE 350) fCP is variable and is age dependent in
Performance of P<0.001 vs VGE/ children <3 years
34 bacterial fCP in bacterial vs control fCP was superior to clinical symptoms (fever,
32 viral viral AGE VGE 49.3µg/g (8.8- stool frequency and vomiting ) and
25 131.1) laboratory (CRP, WBC) in the diagnosis of
unknown Controls 26.5µg/g bacterial AGE.
(14.9-55)
41 healthy
controls fCP≥103.9 µg/g
AUC 0.95 (CI 0.89-
0.98)
CRP≥16.9mg/ml
AUC 0.87 (0.83-0.96)
WBC≥9.5X103
AUC 0.77 (0.69-0.82)
ESR≥15MM/H
AUC 0.84 (0.79-0.89)
AUC fCP vs CRP,

p<0.05
AUC fCP vs WBC,
p<0.001
AUC fCP vs ESR,
p<0.01
AUC fCP vs IL-6,
p<0.001
Opintan Prospective Ghana Outpatient NA Children<5y NA Well nourish Etiology of Bacterial agents NA Ghana EAEC and cryptosporidium were the most
JA, 2010 Cross- 170 AGE vs bacterial AGE isolated University common agents isolated in children with and
sectional 104 Malnurished 161/170 AGE and without diarrhea in this study in children < 5
Aug 2007 controls Fecal lactoferrin 80/104 controls Pfizer- years from Ghana
to May without in AGE vs controls EAEC isolated funds Fecal lactoferrin was significantly elevated in
2008 diarrhea 145/170 diarrhea Virginia children with diarrhea
79/84 controls University
without diarrhea US
f-Lactoferrin, µg/ml
Children with
diarrhea, n=143
1658.9±204.2
Control without
diarrhea, n=84
935.5±194.4
P=0.019
Chen CC, Prospective Taiwan Inpatient NA 117 NA Clinical Fecal lactoferrin AGE etiology NA Chung Fecal lactoferrin is a non-invasive marker
2011 Cross- children severity of as marker of 41/117 RV Shan able to predict bacterial vs viral infection,
sectional Age 3.23y infectious severity of AGE 28/41 NV Hospital and the relative values may be associated
Sept 2008 (3m-10y) diarrhea 31/117 Salmonella Grants with the severity of AGE, corresponding to
to May (Vesikari and 17/117 Vesikari and Clark scores
2010 Clark scores) Campylobacter
f-Lactoferrin, µg/g
RV 2.82±1.27
NV 3.16±1.18
Salmonells 11.17±2.73
(p<0.05 vs viral)
Campylobacter
10.32±2.9
(p<0.05 vs viral)
f-Lactoferrin, µg/g
Severe AGE
11.32±3.29
P<0.05 vs moderate
AGE
P<0.05 vs mild AGE
Moderate 3.77±2.08
Mild 1.51±1.36
AGE=acute gastroenteritis; AUC=area under the curve; BGA=bacterial acute gastroenteritis; CRP=C-reactive protein; EAEC=enteroaggregative E coli; fCP=fecal
calprotectin; NV=norovirus; RV=rotavirus; VGE= viral acute gastroenteritis.
Table 3.3. Does Any Biochemical Test Change the Approach to the Child With Gastroenteritis? (Biochemistry)
Reference Type of Study Countr Inpatient Follow- Population Intervention Comparison Outcome measures Results /Effect size Risk Source of Conclusions and Comments
y Outpatient up of Funding
n/N Bias
Hayajneh Prospective Jordan Inpatient NA 251 children NA Dehydration Clinical and Severe vs mild NA None Historical and clinical characteristics in
WA, 2010 Cross- AGE severity laboratory dehydration: declared this cohort did not correlate with the
sectional Dehydration associations with More hyperNa degree of dehydration
Jan 2007 to Severe 9% severity of 52% vs 3%, p<0.001 Serum urea, creatinine, sodium,
May 2007 Mild 91% dehydration More hyperK potassium and glucose were
17% vs 3%, p<0.001 independently correlated with the
Less isoNa degree of dehydration.
39% vs 95%, p<0.001 Serum urea performed best
Mean urea,mmol/L The results from this study are in conflict
16.2 vs 5.5, p<0.001 with the results from previous studies
Mean and AAP and ESPGHAN guidelines
creatinine,µmol/L
69 vs 38, p<0.001
Mean glucose, mmol/L
5.9 vs 4.7, p<0.001
AUC urea
0.991 (95%CI 0.98-
1.001)
P<0.001
AUC Natrium
0.862 (95% CI 0.74-
0.97)
P<0.001
AUC creatinine
0.850 (95%CI 0.75-
0.94)
P<0.001
AUC Kalium
0.69 (CI 95% 0.55-0.82)
P<0.006
AUC glucose
0.684 (CI 95% 0.57-
0.79)
P<0.007
Steiner MJ, Prospective USA Outpatient Variable 74/79 NA Presence of Urine specific Urine specific gravity NA None Elevated urine specific gravity and urine
2007 cohort study ER Children dehydration gravity, urine correlation with % declared ketones , low urine output were not
Convenience AGE ketones and output dehydration useful diagnostic tests for the
sample Age 17.3m during rehydration r=-0.06, p=0.64 identification of dehydration during the
(3-36m) Urine ketone levels initial assessment of children with AGE
correlation with %
dehydration
r=0.08, p=0.52
Urine output during
rehydration
correlation with %
dehydration
r=0.01, p=0.96
AAP=American Academy of Pediatrics; AGE=acute gastroenteritis; AUC=area under the curve; CI=confidence interval; ER=Emergency room; ESPGHAN=
European Society for Paediatric Gastroenterology, Hepatology, and Nutrition.
HOSPITAL MANAGEMENT
Table 4.1. What are the indications for hospitalization?
Reference Study type QoS Country In/Out Population Randomization Intervention Comparison FU ITT Outcomes Effect Effect size Comments
Patients measures measure (95% CI)
Pockett RD, Retrospectiv +/- UK Inpatients N=1334 children — — Correlation — — Variation of hospital Rates from 0.346 to Hospital admissions
2011 e cohort ≤5 yr of age with with admissions' rates in 0.287 per 10,000 increased as deprivation
study RV-AGE deprivation relation to the (p < 0.001) increased*
rank decrease of a
deprivation
ranking*
*Index of Multiple Deprivation (IMD) 2007 for England
Kyle RG, Retrospectiv + UK Inpatients 24,481 children No No No _ _ Index of Multiple Sperman rho 0.31, p=0.09 There were no
2011 e study (ED) under 15 years Deprivation statistically significant
admitted to ED overcrowding Sperman rho 0.21, p=0.267 relationships between
for breathing the ED admission rate of
houses in poor Sperman rho 0.11, p=0.543
difficulty, fever children admitted for
condition
or diarrhoea diarrhoea and the Index
air quality Sperman rho 0.16, p=0.387
during multiple derivation and
2007/2008. homelessness Sperman rho 0.14, p=0.439 its single indicators.
Freedman Prospective + Canada Inpatients 647 children 3- No No No _ proportion of number and 149/647 (23%, The use of IV rehydration
SB, 2011 cohort study (ED) 48 months 398/4 children treated % range 6-66%) varied dramatically
admitted to 11 46 with IV rehydration among different
different ED. (89%) risk of readmission rate 20% vs 9%, institutions. IV
Exclusion: after IV therapy in p=0.002 rehydration at the index
children already target visit vs no IV visit was significantly
enrolled in other therapy associated with the
studies or Volume of IV fluids range and 15-87 ml/kg, institution providing care
families that variation p=0.003 and was not associated
were Predictors of IV rehydration: with a reduction in the
unavailable/una need for follow-up care
ble to complete institution location OR (95%CI) 3.0 (1.8 –5.0)
telephone vomiting bile or OR (95%CI) 2.6 (1.2–5.5)
follow-up blood
previous physician OR (95%CI) 1.7 (1.0–2.7)
visit
n° vomiting in 24 OR (95%CI) 1.1 (1.0 –1.1) per
hours additional episode
AGE=acute gastroenteritis; ED=Emergency department; OR=odds ratio; QoS=Quality of Study; RV=rotavirus.
Table 4.2. What hygiene and isolation precautions are indicated for a child with AGE?
Reference Study QoS Country In/Out Population Randomization Intervention Comparison FU ITT Outcomes measures Effect Effect size (95% CI) Comments
type Patients measure
Valentini D, 2013 Prospe + Italy Inpatien N=232 — Collection of Coinfections vs 232 — Max. no of diarrhea OR 8.79 (3.32;23.28) p Coinfection with different
ctive ts between 1 clinical data Monoinfections /27 stools/24 h (≥6) (95%CI) <0.001 pathogens is associated with
cohort month and and stool 5 Duration of diarrhea 3.81 (1.47;9.86) p= a more severe course of
study 16 years of samples (days) (≥5) 0.006 symptoms
age Duration of vomiting 7.11 (2.74;18.42)
admitted (days) (≥3) p<0.001
for AGE Fever (≥38°) 17.78 (2.32;136.17)
p=0.006
Severe dehydration 28.70 (3.04;270.6)
(%) p=0.003
AGE=acute gastroenteritis; OR=odds ratio.
Table 4.3. What are the indications for nasogastric rehydration?
Reference Study type QoS Country In/Out Population Randomizatio Intervention Comparison FU ITT Outcomes measures RCT n Effect Effect size Comments
Patients n measure (95% CI)
Freedman Prospectiv + Canada Inpatients N=434 children — Phase1: IV — — Caregivers who did Rates 77% vs 59% Most health
SB, 2012 e cross- (ED) aged 3-48 caregivers rehydration not believe that (p<0.001) care providers
sectional months with were asked to IV/NG insertion is are unfamiliar
study AGE; N=113 complete a easy (NG group vs IV with the use of
health care survey on group) NG
providers nasogastric Caregivers who did Rates 11% vs 3% rehydration
rehydration not believe that (p<0.001) and this
(vs IV). Phase IV/NG rehydration treatment
2: data will replenish fluids choice is in
recorded. (NG group vs IV keeping with
Phase 3: group) caregivers
health-care Estimated pain with Interquartile 80(60-100) vs desires
providers IV/NG insertion s 70(50-90);
completed a according to p<0.001
survey caregivers
‘perception (0=no
pain 100= worst
possible pain) (NG
group vs IV group)
Estimated pain with Median±SD 64±18 vs

NG insertion 52±25 vs
according to health- 50±16;
care providers (0=no p=0.007
pain 100= worst
possible pain)
(Nurses vs Medical
staff vs Fellows)
Estimated Median±SD 24±19 vs
percentage of 11±11 vs
vomiting in children 22±20;
rehydrated with NG p=0.001
according to health-
care providers
(Nurses vs Medical
staff vs Fellows)
Estimated Rates 38% vs 56%
percentage of vs 75%;
shorter ED stay in p<0.001
children rehydrated
with NG according to
health-care
providers (Nurses vs
Medical staff vs
Fellows)
MA (17 ++ High income Inpatients N=1811 (most — ORT orally or IV therapy — — Failure to rehydrate 18(1811) Weighted 0.04 (0.01 to see GL
RCTs) (USA, and trials included via NGT (40- mean 0.07)
Australia, Outpatients children from 50 ml/kg difference
Finland) and 3mo to 5y) administered (95%CI)
low income in 3-6 h) Weight gain (g) at 6 (369) Weighted -26 (-207 to
(Puerto Rico, discharge mean 154) NS
Egypt, difference
Mexico, Iran, (95%CI)
Afghanistan, Percent weight gain 5 (767) Weighted -0.26 (-1.56
Colombia, (g) at discharge mean to 1.05) NS
Peru) difference
(95%CI)
Length of hospital 6 (526) Weighted -1.2 (-2.38 to
stay mean -0.02) ↓
difference
(95%CI)
Incidence of 2 (248) NS
hyponatremia
Incidence of 10 Weighted 0.0 (-0.01 to
hypernatremia (1062) mean 0.01) NS
difference
(95%CI)
Duration of diarrhea 8 (960) Weighted -5.9 (-12.7 to

(h) mean -0.89) ↓
difference
(95%CI)
Total fluid intake 8 (985) Weighted 32.1 (-26.7 to
(ml/kg) at 6h mean 90.9) NS
difference
(95%CI)
Total fluid intake 7 (835) Weighted 73.45 (-31.8
(ml/kg) at 24h mean to 178.7) NS
difference
(95%CI)
Phlebytis More often
with IVT
Paralytic ileus More often
with ORS but
NS
Varavithya RCT - Thailand Inpatients N= 22, 4–17 NO Nasogastric IV 22/22 Yes Weight gain — Similar
W, 1978 months of age, Rehydration rehydration Stool loss weight gain,
moderate (150 with 5% Oral intake oral intake,
dehydration mL/kg/day - dextrose 0.3% Blood Sodium and
10–20 Na+ (150 Osmolarity improvement
mL/kg/h for 2 mL/kg/day - Serum specific in laboratory
h, then a 10-20 gravity test results
costant rate mL/kg/h for between
over 22 h) 2h, then a groups;
costant rate sodium and
over 22h) osmolarity
returned to
normal
without
complications
in both
groups**
Hidayat S, RCT - Indonesia Inpatients N=75 , 1–59 NO Nasogastric IV 75/75 Yes Weight gain — Rates No
1988 months of age, rehydration rehydration: difference**
severe (WHO lactated Hourly assessment of Rates No
dehydration standard Ringer's degree of difference**
(WHO) ORS) 40 solution (40 dehydration
ml/kg in the mL/kg X 1h, 4-h assessment of Rates No
first hour, 30 then 30 degree of difference**
ml/kg in the mL/kg X 1h, dehydration
second, 20 then 20 Mean hospital stay Mean No
ml/kg in the mL/kg X 2h) difference difference**
third and Duration of vomiting Mean No
fourth hours difference difference**
Pignatelli S, Prospectiv + Burkina Faso Inpatients N=4131 < 5y of — Nasogastric — — Yes Increased weight at — Rates 3717/4131 Safe and
2000 e cohort age with acute rehydration 4-5 h (%) (90%); p<.001 effective in the
study diarrhea and (50-100 Longer period of Rates 413/4131 treatment and
severe mL/kg/day infusion (%) (10%) prevention of
dehydration for the first dehydration in
10 kg of developing
weight and countries
25 to 50
mL/kg per
day for the
remaining)
Powell CV, Non- + Australia Inpatients N=254 , 6-72 Appropriate Rapid Standard 207/25 NO Additional loss of Rates 2.6% (-5.3% No differences
2011 inferiority (ED) months of age, Nasogastric Nasogastric 4 >2% compared with Difference to 10.5%); between
RCT moderate Rehydration Rehydration admission weight (95%CI) p=0.524 groups (Rapid
degree of (100 ml/kg (according to in 4h vs 24
dehydration ORS in 4 h) the % of hours) in
(Gorelick) weight loss) terms of
Inability to tolerate Rates 0.8% (0-2.4)
efficacy and
the insertion of NGT (95%CI) vs 1.8% (0-
safety.
4.4); p=0.51
However, even
Persistent vomiting Rates 5%(1.0-9.0) if RNR
(95%CI) vs 2.8%V(0- administered
5.9%); p=0.38 in ED could
Commencement of Rates 5.9% (2.9- reduce the
IV rehydration (95%CI) 11.7) vs 4.9% need of
(2.0-10.3); hospitalization
p=0.66 , discharge
Continued signs of Rates 18.4%v(11.4- failed in about
moderate (95%CI) 25.4) vs one fourth of
dehydration (>3 28.4% (19.6- patients.
clinical signs) 37.2) p=0.08 Limits: ITT is
Need for NGT fluids Rates 9.2% (3.7- missing;
beyond 24 hours (95%CI) 14.7) 21/254
(SNR only) patients were
lost at FU and
no reason
provided;
single-blinding
**Rouhani
AGE=acute gastroenteritis; ED=emergency department; IV=Intravenous; NG=Nasogastric; NGT=Nasogastric tube; NS= Not significant; ORS= Oral Rehydration
Solution; QoS=Quality of Study; RNR=rapid nasogastric rehydration; SNR=standard nasogastric rehydration.
4.4. What are the indications for intravenous rehydration?

Table 4.4.1 Composition
Reference Study QoS Country In/Out Population Randomization Intervention Comparison FU ITT Outcome Effect Effect size Comments
type Patients measures measure (95% CI)
Neville KA, 2006 RCT + Australi Inpatients 124 children with Not clearly IV rehydration IV 102/12 Not clear Change in [Na] mean (SD) 0.4 (1.7) vs Hypotonic saline
a (ED) AGE (62 per described with 0.45% rehydration 4 mmol/L in 2.4 (2.0), solutions
group). Exclusion saline in 2.5% with 0.9% hyponatremic p=0.003 exacerbate the
criteria: Renal or dextrose (N/2) saline in patients (N/2 vs tendency to
pulmonary 2.5% NS) develop dilutional
disease, dextrose Change in [Na] mean (SD) -2.3 (2.2) vs hyponatremia
abnormal ADH (NS) mmol/L in +0.8 (2.4), while isotonic
secretion, ADH normonatremic p<0.001 solutions are
active drugs, patients (N/2 vs protective. The
pituitary/hypotal NS) maximum
amic disease. [Na] decrease > 2 prevalence 13% vs 0% decrease in [Na]
mmol/L in was of 6mmol/L
hyponatremic in the 2 patients
patients (N/2 vs treated with
NS) rapid hypotonic
[Na] decrease > 2 prevalence 51% vs 13% rehydration
mmol/L in
normonatremic
patients (N/2 vs
NS)
Hanna M, 2010 Retrosp +/- USA Inpatients 141 records of _ 10-40 ml/kg _ _ _ Development of prevalence 18/97 18,5% developed
ective patients fluids hyponatremia (18,5%) a mild
study admitted for AGE containing 5% hyponatremia
having at least dextrose in 0.2, (Na 133,4±0,9
two registration 0.3 or 0.45 % mEq/L)
of serum saline.
electrolytes.
Han JJ, 2009 RCT +/- Korea Inpatients 33 neonates Not clearly 10 ml/kg of 5% 10 ml/kg of 33/33 Not Weight gain mean % of 5.08±6.33 vs No differences
with acidosis described Albumin 0.9% normal reported (Albumin vs weight 5.67±5.73, either in the pH,
secondary to saline normal saline) gain±SD p=NS BE and HCO3
AGE (Ph<7.25 or Length of stay mean 8.13±3.23 vs levels, in the
BE-15). In (Albumin vs days±SD 9.36±4.16, body weight and
addition to normal saline) p=NS weight gain 4
interventions, all Persistence of rate 80% vs days after

patients received acidosis after 3 h 61.1%, p=NS treatment or in
maintenance rehydration the length of
with 5% hospital stay.
dexstrose and
NaCl 20 mEq/L,
correction of
acidosis and
potassium
supplementation
.
Levy JA, 2007 Case- +/- USA Inpatients 56 cases and 112 _ _ _ _ _ Risk of return visit OR [95%CI] 3.9 [1.8 to children who
control (ED) controls arriving with admission 8.7] received more IV
study at the ED for for children dextrose
dehydration due receiving no independently
to AGE. Cases dextrose- from fluid
were those containing fluids amount, were
children Risk of return visit OR [95%CI] <500 less likely to have
requiring return with admission mg/kg=3.0 a return visit
visit with for children [1.6 to 5.8] requiring
admission receiving no <750 admission.
dextrose- mg/kg=3.7
containing fluids, [1.7 to 8.1]
according to fluid <1000
amounts mg/kg= 5
[1.7 to 14.9]
Hoorn EJ, 2004 Observa Canada Inpatients 40 children who _ _ _ _ _ Electrolyte free 2±2 vs 1±1, Cases received 3-
tional had a hospital- water received p=0.001 fold more
study acquired (cases vs controls) elecrolyte free
hyponatremia water than
(Na<136 controls and had
mmol/L) a greater positive
compared with fluid balance than
non- the control group
hyponatremic (P=0.02). No
patients who had significant
at least 2 [Na] differences
evaluation related to the
during their stay underlying
(1:3 ratio) disease.
Saba TG, 2011 RCT + Canada Inpatients 59 children (34 Adequate IV rehydration IV 12/25 not Rate of change in median [IQR] 0.20[0.03 to The absolute
surgical and 25 with 0.9% rehydration medica performe [Na] 0.4] vs 0.08[- change in [Na]
medical, NO Saline in 5% with 0.45% l and d 0.15 to 0.16] was greater for
AGE) aged 3 dextrose saline in 5% 25/34 Number of number (%) 3 (19%) vs 5 0.9% saline group
months to 18 (Isotonic) dextrose surgical patients with (24%) compared with
years admitted (Hypotonic) patient decrease in [Na] the 0.45% group
to ED for medical s Hyponatremia number (%) 1(6%) vs 1 (+3mmol/L vs +1
or surgical [Na<136] (5%) mmol/L), but not
problems. Hypernatemia statistically

Exclusion [Na>145] significant
criteria:
electhrolyte
alterations,
neurological,
cardiac or renal
illness, edema
and diuretic
drugs use.
Yung M, 2009 4 arms +/- Australi Inpatients 50 children Adequate Rehydration Rehydration 50/50 not Overall [Na] fall mean mmol/L 2.3 (+ 4.0) The change in
RCT a (PICU) admitted to PICU with 0.9% with 4% performe [Na] fall difference 3.0 (0.8– [Na] was
for different saline dextrose d difference (95%CI) in 5.1), significantly
reasons (37 (Isotonic). and 0.18% (hypotonic vs mmol/L p=0.006 affected by fluid
surgery, 15 of Subdivision in saline isotonic) type (P = 0.0063)
them ventilated). two groups 1. (hyposmolar). [Na] fall difference 1.6 (-0.7, but not fluid rate
NO AGE full Subdivision in difference full (95%CI) in 3.9), p=NS (P = 0.12). Among
maintenance two groups 1. (maintenance vs mmol/L surgical patients,
regimen and 2. full restricted) there were
restricted maintenance significantly
fluids regimen and 2. greater falls in
restricted fluids mean [Na] for
hyposmolar
compared with
isosmolar fluids:
4.4 (1.9, 6.8)
mmol/L, P =
0.0009
Akech SO, 2010 Phase II + Africa Inpatients children with Isotonic fluids
RCT severe were associated
malnutrition and with modest
shock, septic improvement
shock BUT Not when compared
DUE TO AGE . to half-strength
Darrow's in 5%
dextrose
ADH=Antidiuretic hormone; AGE=acute gastroenteritis; ED=emergency department; IV= intravenous; QoS=Quality of Study SD=standard deviation.
Table 4.4.2. Regimen

Reference Study type QoS Country In/Out Population Randomization Intervention Comparison FU ITT Outcomes Outcome Effect size Comments
Patients measure (95% CI)
Freedman SB, Overview of ++ High and In and 95 unique All studies Oral IV - - Length of stay (6 Mean −1.20 (−2.38 to
2013 4 systematic middle outpatient randomized included in the rehydration rehydration trials = 526 difference −0.02)
reviews of income s controlled trials review were patients)
RCTs (3 (N=12478) RCTs
cochrane 87 randomized
Complication Risk −0.02 (−0.04 to
reviews) controlled trials
(phlebitis) difference −0.01)
included subjects
< 18 years (N =
10 954)
Freedman SB, RCT + Canada Inpatients 224 children Adequate IV rehydration IV Yes Change in Mean±SD 1.6±2.4 vs Large volume IV fluids does
2013 (ED) (114 intervention with 60 ml/kg rehydration sodium levels 0.9±2.2 not promote the
group vs 110 0.9% saline with 20 (mEq/L) (p=0.04) development oh
control group) solution in 1 h ml/kg 0.9% (60mL/Kg vs 20 hyponatraemia
aged 3 months- followed by 5% saline mL/Kg)
11 years with dextrose in solution in 1 Sodium decrease Rates 8/112 (7%) vs
dehydration 0.9% saline at h followed ≥2 mEq/L from 17/105 (16%);
(CDS>3) due to a maintenance by 5% 0-4 h (p=0.04)
AGE and no rate. dextrose in
response to ORT. 0.9% saline
Exclusion at a Sodium increase Rates 59/112 (53%)
criteria: maintenance ≥2 mEq/L from vs 39/105
underlying rate. 0-4 h (37%);
chronic diseases. (p=0.02)
Freedman SB, RCT + Canada Inpatients 226 children Adequate IV rehydration IV Yes Rehydration absolute 6.5% (CI 5.7% Children were moderately
2011 (ED) (114 intervention with 60 ml/kg rehydration (CDS<1) within 2 difference to 18.7%, dehydrated. No difference
group vs 112 0.9% saline with 20 hours after (95%CI), p=0.32) in major outcomes between
control group) solution in 1 h ml/kg 0.9% treatment NNT NNT=15 the two treatment arms
aged 3 months- followed by 5% saline Prolonged IV absolute 8.9% (CI 21% was found. No relevant
11 years with dextrose in solution in 1 treatment difference to -5%, p=0.19) benefit of the rapid
dehydration 0.9% saline at h followed (95%CI) rehydration regimen.
(CDS>3) due to a maintenance by 5% Clinical rate p=0.96 Time to discharge was
AGE and no rate. dextrose in dehydration slightly higher in rapid
response to ORT. 0.9% saline scores dehydration group although
Exclusion at a Time to mean time 6.3 h vs 5 h it did not achieve
criteria: maintenance discharge (h) (p=0.03) significance settled at 0.01
underlying rate. Physician 5 point 61(54) vs 74 (6.3 h vs 5 h, p=0.03)
chronic dieases. comfort to Likert scale (66), p=0.06
discharge within
4 hours (Rapid vs
standard group)
Nager AL, RCT + USA Inpatients 88 children aged Adequate IV rehydration IV 88/ No mean weight (g) Mean (%) 474 (4.2%) vs Early discharge for cases (2
2010 (ED) 3-36 months with 50 ml/kg rehydration 88 gain (% of 408 (3.8%), h vs 4 h). No difference
with moderate 0.9% saline in with 50 weight), rapid vs p=0.34 between the two groups for
dehydration due 1h ml/kg 0.9% standard group all the outcomes.
to AGE. saline in 3 h Return visits Frequency 15.6%(6.5 to

Exclusion (95%CI) 29.5) rapid vs
criteria: 14% (5.3 to
electrolyte 28), p=0.99
alteration, Electrolyte single values NS difference
severe alteration
dehydration/sho
ck, surgical
conditions.
Freedman SB, Prospective + Canada Inpatients 647 children 3- No No No _ proportion of number and 149/647 (23%, The use of IV rehydration
2011 cohort study (ED) 48 months 398 children treated % range 6-66%) varied dramatically among
admitted to 11 /44 with IV different institutions. The
different EDs. 6 rehydration volume of IV fluids
Exclusion (89 Frequency of rate 20% vs 9%, administered also varied
criteria: children %) readmission in p=0.002 according to site (P .003),
already enrolled patients with a range between 15
in other studies undergoing IV and 87 ml/kg).
or families that therapy vs no IV
were therapy
unavailable/unab Volume of IV range and 15 -87 ml/kg,
le to complete fluids variation p=0.003
telephone Predictors of IV rehydration:
follow-up institution OR (95%CI) 3.0 (1.8 –5.0)
location
bilious or bloody OR (95%CI) 2.6 (1.2–5.5)
vomiting
previous OR (95%CI) 1.7 (1.0–2.7)
physician visit
n° vomiting in 24 OR (95%CI) 1.1 (1.0 –1.1)
h per additional
episode
Moineau G, Prospective - Canada Inpatients 17 children with No 30 ml/kg 3.3% _ 17/ no No patients required
1990 Cohort study (ED) isonatremic dextrose + 17 hospitalization. Only one
mild-to- 0.3% saline patient required a new
moderate over 3 h course of rapid IV
dehydration due rehydration.
to AGE, aged 1-6
years
Success of percentage ORT 55.6% vs Initiating treatment with
treatment at 4 of IV 56.8%, RD= - ORT was quicker than with
hours (defined as responders 1.2% [95%CI - IVT. ORT gained less weight
resolution of and risk 24% to 21.6%] than IVT
dehydration, difference
weight gain,
correction of
urine output,
absence of
severe emesis)
Spandorfer RCT + USA Inpatients 73 children (ORT Adequate Oral IV 67/ yes Time to initiate time and ORT 15 min vs
PR, 2005 (ED) 36 vs IV 37) aged rehydration rehydration 73 therapy difference IV 36 min, RD
< 3 years (mean with 50 ml/Kg with 2 bolus (3 [95%CI] 21.2 [CI 10.3 to
age 15 m) with (for of 20ml/Kg ORT 32.1]
moderate dehydration saline ,3 Improvement of % of ORT 78.8% vs
dehydration score 3,4,5) or solution in 1 IVT) dehydration responders IV 80%, RD -
(Gorelick score) 75 ml/Kg (for h. Then oral after 2 h and 1.2% [95%CI -
secondary to score >6) rehydration difference 20.5% to 18%]
AGE. Exclusion hyposmolar for 3 h Hospitalization rate ORT 30.1% vs
criteria: ORS rate IV 48.7%, RD -
hypotention, 18.1% [-40.1%
diarrhea > 5 d, to 4%]
chronic illnesses,
malnutrition
Phin SJ, 2003 Prospective +/- Australia Inpatients 145 children _ Pathway Hystoric _ _ discharge in 8 h rate 61.3% vs rapid rehydration in
study with (ED) aged 6 months including oral pathway, IV (mild 72.7%, p=NS children moderately
historical to 16 years, with administration rehydration dehydration) dehydrated is effective in
controls AGE < 48h of fluids in 1 h over 24 h discharge in 8 h rate 44.2% vs 3.7%, reducing admission rate and
prospectively followed by 20 and NGT (moderate p<0.001 lengths of stay in ED
enrolled, 170 ml/kg/h of rarely used. dehydration)
historic controls. 0.45% + 2.5% admission rate rate 26.9% vs
Exclusion dextrose or (mild 25.9%, p=NS
criteria: bloody Gastrolyte per dehydration)
stools, bilious NGT. admission rate rate 55.8% vs
vomiting, chronic (moderate 96.3%,
medical dehydration) p<0.001
conditions. procedure rate rate 62.4% vs
(mild 23.9%,
dehydration) p<0.001
procedure rate rate 94.2% vs
(moderate 88.9%, p=NS
dehydration)
Reid SR, 1996 Prospective USA Inpatients 58 patients aged _ 20-30 ml/kg _ _ _ All patients demonstrated
cohort study (ED) 6 months to 13 isotonic improvement of hydration
years (median cristalloid degree. 28% did not
age 22 months) solution IV in tolerate ORT and were
with moderate 1-2 h followed admitted to continue IVT.
dehydration by 30-90 ml of No complications were
ORT registered during IVT.
AGE=acute gastroenteritis; ED=emergency department; IVT=Intravenous therapy; NGT=Nasogastric tube; ORS= Oral Rehydration Solution; ORT=Oral
rehydration therapy; QoS=Quality of Study.
Table 4.4.3. Treatment of hypernatremia
Reference Study type QoS Country In/Out Population Randomization Intervention Comparison FU ITT Outcomes Effect Effect size Comments
Patients measures measure (95% CI)
El- Retrospective + Egypt Inpatients 48 children (mean _ No Intervention. _ _ _ risk of mortality OR (95%CI) 3.3 (1.5 to Serum Na should be lowered
Bayoumi study (PICU) age 21.8 m) with AGE Rehydration regimen: in children 7.2) slowly with rate of 0.5mEq/L/h.
MA, 2012 and hypernatremic Fluid bolus of 20ml/kg receiving > 40 No difference in [Na] between
dehydration 0.9% saline in 20 min ml/kg initial fluid children who presented seizures
[Na]>150 (mean 163 followed by 48h infusion bolus and not.
mmol/L). Exclusion of 25-50 ml/kg/day of risk of seizures rate 6.3%
criteria: renal failure 0.9% saline in 5% Hourly delta of mean delta 0.58
and diseases dextrose. Velocity was 4 Na 0-6 h (mEq/L/h) seizures vs
ml/kg/h first 10 Kg, 2 0.52 not
ml/kg/h 10-20 kg and (p=0.08)
1ml/kg/h above 20 kg. Hourly delta of mean delta 0.65
Na 0-24 h (mEq/L/h) seizures vs
0.51 not
(p=0.02)
Hourly delta of mean delta 0.63
Na 6-24 h (mEq/L/h) seizures vs
0.51 not
(p=0.037)
Robertson Retrospective South Inpatients 57 children with _ No intervention: _ _ _ Median rate of velocity 0.6 The majority of children in this
G, 2007 study Africa (PICU) hypernatremia Maintenance according Na fall mmol/L/h study received a hypotonic IV
(Na>145, meadian to Holliday-Segar + 50 Incidence of p=0.43 infusion containing 61 mmol/L
165 mmol/L) ml/kg/day for seizures (fall <0.6 sodium. Although univariate
moderately dehydrated group vs >0.6 analysis demonstrated a non-
children and 100 mmol/L/h group) significant trend towards a
ml/kg/day for severely Incidence of p=0.31 more rapid fall in serum sodium
dehydrated with half adverse event in children who received
Darrow's Dexstrose (5% (fall <0.6 group solutions containing <61
dexstrose and 61 mEq/L vs >0.6 mmol/L/h mmol/L of sodium, this was not
Na) group) associated with a difference in
Mortality Percentage 7% outcome.
Sharifi J, RCT +/- Iran Inpatients 470 children aged 1- Not NGT rehydration 40 IV 20-30 No Seizures in rate (%) 2/34 (6%) ORT through NGT is successful
1985 (PICU) 18 months admitted appropriately ml/kg/h (max 400 ml/h) ml/Kg/h Ringer hypernatremic vs 6/24 in treating severe dehydration
for severe AGE described ORS for 6 h followed by Solution patients treated (25%), due to AGE and superior to IV
maintenance per os or followed by with NGT vs IV p=0.05 therapy in reducing the
NGT with hypotonic ORS maintenance rehydration complications associated with
fluids for 48 h the treatment of
hypernatremia. Methodological
limitations: protocol,
randomization and allocation
concealment not described.
AGE=acute gastroenteritis; NGT=Nasogastric tube; ORS=oral rehydration solution; QoS=Quality of Study.
Table 4.5. When to discharge a child admitted because of gastroenteritis
Reference Study type QoS Country In/OutPatients Population Randomization Intervention Comparison FU ITT Outcomes Effect measure Effect size Comments
measures (95% CI)
Patel B, 2009 Intervention +/- US ED Patients aged No Written Standard _ No Recall of 7 warning Mean (95%CI) 3.5 (3.26- Verbal reinforcement
study 3 months to 18 discharge discharge signs and symptoms 3.78) vs 4.1 of written discharge
years with instructions group vs assessed 24 to 48 (3.83-4.43) instructions by a
reinforced interventio hours after the ED bilingual DF improves
verbally by the n group visit (English parental recall of
bilingual speakers) discharge instructions
discharge Recall of 7 warning Mean (95%CI) 3 (2.67- for gastroenteritis.
facilitator signs and symptoms 3.36) vs 4.5
assessed 24 to 48 (4.18-4.88)
hours after the ED
visit (Spanish
speakers)
Callery P, 2010 Retrospectiv + UK Inpatients (ED) All children No No No No No Rate of readmission after same day discharge The total number of
e under 15 years Overall Kendall's tau 0,61, admissions to
of age p=0,007 hospital in the year
discharged Respiratory illnesses Kendall's tau 0,83, was associated with
following p<0,001 its readmission rate
emergency Feverish illnesses Kendall's tau 0,50, (Kendall's
admission for p=0,023 tau(b)=0.71,
breathing Acute diarrhea Kendall's tau 0,37, p=0.002). Variations
difficulty, p=0,098 between hospitals
feverish illness suggest that other
and/or factors can also affect
diarrhea readmission rates.
during
2005/2006
(n=20,354) or
2006/2007
(n=23,018)
DF= discharge facilitator; ED=emergency department; QoS=Quality of Study.
Table 4.6. Can any therapeutic intervention reduce the length of hospital stay?
Reference Study QoS Country In/OutPatients Population Randomization Intervention Comparison FU ITT Outcomes RCT Effect Effect size Comments
type measures (n/N) measure (95% CI)
Dupont C, 2009 RCT + Peru and Outpatients and N=602 (1-36 DB Smectite (6-12 Placebo. - Yes Duration of - - - Peru: lower 72-hour
Malaysia Inpatients mo) g) diarrhea (hours) cumulative stool output
(P=0.032); shorter
duration of diarrhea
(P=0.001).
Malaysia: lower 72-hour
stool output (P=0.007);
shorter duration of
diarrhea (P=0.001).
Mujawar QM, RCT +/- India ED N=117 (2-5 y) Single blinded Diosmectite no - - Duration of - - - Shorter time for
2012 with AGE. (4.5 g/d for 5 intervention diarrhea resolution of diarrhea
d) (P<0.001).
Lehert P, 2011 MA ++ high- or Outpatients and (9 RCTs, Heterogeneous Racecadotril placebo or - - Patients with 9 HR (95%CI) 2.04 (1.85 to Proven effective in
middle- Inpatients n=1384, 1 (typically 1.5 equivalent (in recovery defined as 2.32)P<0.001 reducing the duration of
income mo- 15 y) mg/kg TID) particular, patients with a symptoms in children
countries kaolin-pectin) diarrhea duration with AGE
of less than 2 days
Macgillivray S, MA ++ high- or Inpatients (1 N= 2973 Heterogeneous Lactose-free Lactose- - Yes Duration of 16/29 Mean -17.77(25.32 In young children with
2013 middle- outpatient) children aged milk, milk containing diarrhea (hours) difference to 10.21) vs acute diarrhea who are
income two months products, or milk, milk (range) (28.8 to 230) not predominantly
countries to 59 foodstuffs products, or Treatment failure 18/29 Relative 0.52 breast-fed, change to a
Months (29 foodstuffs effect (0.39 to lactose-free diet may
RCT) (95% CI) 0.68) result in earlier
Need for 1/29 Relative 0.79 resolution
hospitalization effect (0.09 to of acute diarrhea and
(95% CI) 6.65) reduce treatment
failure. Diluting lactose-
containing formulas may
also have some benefits
but further trials are
required to have
confidence in this
finding. However data
were different in
outpatients setting.
Szajewska H, MA ++ High In and N= 2963 5 unclear Daily Placebo (10) _ Yes Duration of 12/15 Mean –1.11 [–1.91, LGG reduces the
2013 income outpatients patients doses of LGG diarrhea in days. (95%CI) –0.31] and – duration of diarrhea
(Europe) (1603 in the ranging from (High dose and low 0.90 [–2.50, either in terms of days
and low experimental 1.2 x 108 CFU dose). 0.69] and hospitalization
income group and to 2 x 1012 CFU Duration of 11/15 Mean –1.27 [–2.04,
1360 in in addition diarrhea in days. (95%CI) –0.49]
the control to rehydration Setting (Europe and
group)  15 therapy and –0.87 [–
non-Europe).
studies 1.81, 0.08]
Hospitalization in 4/15 Mean –1.42 [–3.05,
days. (95%CI) 0.21]
Dinleyici EC, MA ++ high- or Inpatients 13 RCTs Heterogeneous S boulardii Placebo or no Yes Yes Duration of n=449 Mean -0.84 (-1.14 administration of this
2012 middle- intervention hospitalization difference to -0.54) probiotic strain may
income (95%CI) reduce the duration of
countries hospitalization in
inpatient children
Freedman SB, Overview ++ High and In and 95 unique All studies Probiotics Oral - - Length of stay 10 trials Mean −1.12 (−1.16
2013 of 4 middle outpatients randomized included in the rehydration = 1932 difference to −0.38)
systemati income controlled review were patients
c reviews trials RCTs
of RCTs (N=12478)
(3 87
cochrane randomized
reviews) controlled
trials included
subjects < 18
years (N = 10
954)
Piescik-Lech M, RCT + LGG (6 x 109) LGG plus 81/ Yes Duration of - Median 1 (0–1) vs 1 LGG plus smectite and
2013 plus scmectite Placebo 87 intravenous (range) (0–3) p=0.02 LGG alone are equally
therapy after effective for treating
randomization, young children
days with AGE. Combined use
Duration of No of the two interventions
hospitalization difference is not
after justified.
randomization,
days
Vomiting, number No
difference
Need for Number (%) No
hospitalization difference
Rautenberg TA, cost + UK Outpatients 10 individual - Racecadotril + ORS - - Total incremental Probabilistic +0.0008 Considering the best
2012 utility studies, 2 SR ORS QALY gain sensitivity available evidence,
analysis and 2 MA analysis racecadotril is cost
Drug cost Cost results £12.17 vs effective in the
£3.03 treatment of AGE in
Primary care £51.12 vs children
£62.64
Secondary care £40.20 vs
£416.82
Adverse events £0.35 vs
£0.46
Total mean cost £103.84 vs
per patient £482.95
AGE=acute gastroenteritis; LGG= Lactobacillus rhamnosus GG; ORS=Oral rehydration solution; QALY=quality adjusted life year.
TREATMENT
Table 5.1. Rehydration
Reference Intervention Randomization Allocation concealment Blinding ITT analysis Population Main results
(experimental group vs. control group)
Santucci KA, Frozen solution (FS) (Revital-ICE, PTS Prospective controlled crossover trial. N=91 (6 months to Children with mild or moderate dehydration are
1998 Labs, Deerfield, Ill) vs conventional 13 years of age) more likely to tolerate FS than CS. Conventional
glucose electrolyte solution (CS) children with AGE solution failures crossed over to FS had a greater
seen in pediatric ED tolerance rate than the reverse.
Freedman SB, ORS with 2 sucralose- Adequate Adequate DB + N=66 (5-10 y), Sucralose-sweetened ORSs significantly more
2012 improved sweetened ORSs vs. healthy children palatable (P<0.001).
taste rice syrup solid ORS
Diez-Gandia 4 ORSs (cola, Adequate No Single-blinded Yes N=116 (6-9 y), Preference for cola (rated as good or really good by
A, 2010 strawberry, fruit, healthy children 87.9%) and strawberry flavor (62.1%).
neutral)
Piescik-Lech Apple taste ORS vs. Adequate Adequate DB No (ACA) N=130 (4-48 mo) Similar resolution of signs of dehydration (P=0.28),
M, 2012 regular taste ORS children with AGE adequate weight gain (P=0.48), urine production at
24 h (P=0.95).
Wadhwa N, ORS with zinc ORS with vs. ORS Adequate Adequate DB Yes N=500 (boys, 1-35 Similar stool output (P=0.25); no difference or
2011 without zinc (40 mo) reduction in recovery time (HR 1.06, 95%CI 0.88 to
mg/L) 1.27).
Passariello A, ORS with zinc ORS with zinc (1 Adequate Adequate SB Yes N=119 (3-36 mo) Higher resolution of diarrhea at 72 h (P=0.01);
2011 and mmol/L) & reduced number of daily outputs at 24 h (P=0.002).
prebiotics prebiotics vs.
standard ORS
Gregorio GV, ORS with Polymer-based ORS Of the 34 trials, the methods used to generate the allocation sequence were adequate MA (34 RCTs, Fewer unscheduled intravenous infusions in the
2009 polymers vs. glucose-based (computer-generated or random-numbers table) in 24 trials and unclear in the remaining 10 n=4214; 27 RCTs in polymer-based ORS group compared with glucose-
ORS trials. Less than half of the trials (12) used an adequate method to conceal allocation. The children) based ORS (ORS ≥ 310 and ≤ 270 groups combined)
method was unclear in the other 22 trials. (RR 0.75, 95% CI 0.59 to 0.95; 2235 participants, 19
Blinding of the participants, providers, and assessors was only done in three trials. Blinding was trials).
difficult or impossible in most trials because of the difference in the appearance of the ORS
formulation after reconstitution. Wheat-based ORS resulted in lower total stool
All but two trials included an adequate (> 90%) number of randomized participants in the output in the first 24 hours compared with ORS ≤
analysis. The number was assessed as inadequate in two trials. 270 (MD -119.85 g/kg, SD -114.73 to -124.97; 129
participants, 2 trials). Adverse effects were similar
for polymer-based ORS and glucose-based ORS.
Alam NH, ORS with L- ORS with vs. ORS Adequate Adequate DB Yes N=50 (boys, 6-36 Reduced stool output on day 3 (P=0.03); smaller
2011 isoleucine without L-isoleucine mo) ORS intake on day 1 (P=0.04); similar duration of
(2 g/L) diarrhea (P=0.96).
Abdulrhman ORS with ORS with vs. ORS N=100 (aged approx. Reduction in vomiting (P<0.001) and diarrhea
et al. 2010 * honey without honey 1.3 y) frequency (P<0.05).
*Article not entirely accessed
Esteban Gelatin Gelatin tannate + No – observational study - - No 239 children aged 3 Stool decrease index ORS
Carretero J, tannate + ORS ORS vs ORS alone months to 12 years -0.1894 vs ORS + gelatin tannate -0.6023
2009 with AGE (mean age (p<0.0001). The two groups of treatment differ at
2.3 y) baseline with controls having more stools per day.
AGE=acute gastroenteritis; ORS=Oral rehydration solution.
Table 5.2. Nutritional management
Reference Type of Country In/Out FU n/N Population Intervention Comparison Outcome Results Risk of Bias Source of Conclusions and
Study Patients measures /Effect size Randomization Allocation Blinding ITT Funding Comments
Concealment
Gregorio Systematic 16 10 trials Variable 12 trials, Early Efficacy Primary: Early vs Late All studies were Yes – 2 No – 11 Yes, Different The present
GV, 2011 review countri Inpatient 1226 refeeding and Duration of Refeeding RCT studies studies Yes for sources: meta-analysis
es 2 trials children < 12h vs Adverse diarrhea (7 Duration of Unclear -10 – 1 study, all Industry did not provide
Europe, Outpatien AGE 0-5 Late effects Secondary: diarrhea studies single outc Academi evidence that
USA, t years 724 refeeding Stool 7/12 trials, blinding ome c WHO early refeeding
Africa, early 502 >12h output 685 particip s–5 increases
Asia late Different Weight MD -6.90 h,CI trials unscheduled
refeeding feedings gain IV -18.70 to Yes, use of IV fluids,
fluids 4.91 for episodes of
Vomiting Unscheduled som vomiting, and
IV fluids e development of
6/12 trials, outc persistent
813 particip ome diarrhea. The
RR 0.87, CI s–7 results support
0.48 to -1.59 trials existing practice
Stool output of early
24-48h 3/12 refeeding during
trials No or after start of
difference rehydration of
Weight gain patients. No
after 24h conclusion could
3/12 trials No be made
difference regarding the
Vomiting duration of
5/12, 456 diarrhea.
participants
RR 1.16, CI
0.72 to 1.86
Saneian H, Prospective Iran Outpatient 7 days 71 Children Refeeding Advantages Time to Diarrhea No NA NA Not Isfahan Early
2012 controlled AGE Mean with of relief from relief, days repo Universit administration
trial Jan age Lactose- refeeding diarrhea Lactose-free rted y Grant of lactose-free
2009 to Aug 7.1±3.7m free vs lactose- vs lactose formula for
2009 1-24 Lactose free 1.7±0.7 vs formula fed
months containing formula 2.6±0.7 children
Formula formula 95%CI 1.5 to presenting with
fed 3.9, p<0.001 AGE can result
P<0.001 in a more rapid
relief of
diarrhea
However there
were baseline
differences
between the
groups (more
days with
diarrhea in the
intervention
group,p=0.047,
more severe
dehydration in
the control,
p=0.015)
Rabbani DB-RCT Banglad Inpatient 73 Children Cooked Effect on Success Effect of GB Yes- computer Yes- Yes- Not None GB diet
GH, 2009 Sept 2004 esh Shigella AGE 6- green diarrhea rate on stools: generated Investigators Investigato repo declared improved
to May 60mAll addition of severity Reduction of random and patients rs and rted clinical severity
2005 treated banana volume number patients of childhood
Ciprofloxacin (GB) Reduction of Shigellosis and
250g/L numbers/d can use as a
in children Clearance of simple and
with blood, mucus useful adjunct
Shigellosis Reduction of for dietary
fever management of
Reduction of AGE Shigellosis
ORS volume
GB vs control
Clinical
success
85.3% vs
66.7%,
p=0.001
Clinical
failure 14.7%
vs 33.6%, p=
0.05
Macgillivr MA ++ high-or Inpatient N= 2973 Lactose- Lactose- Duration of Mean Yes Heterogeneo Heterogen Yes Universit In young
ay S, 2013 middle- s (1 children free milk, containing diarrhea difference us eous y of children with
income outpatie aged two milk milk, milk (hours) (range): - Dundee, acute diarrhea
countries nt) months to products, products, 17.77 (25.32 UK. Hull who are not
59 Months or or to 10.21) vs York predominantly
(29 RCT) foodstuffs foodstuffs (28.8 to 230) Medical breast-fed,
Treatment Relative School change to a
failure effect and NIHR lactose-free diet
(95% CI) 0.52 Centre may result in
(0.39 to 0.68) for earlier
Needfor Relative Reviews resolution of
hospitalization effect and acute diarrhea
(95% CI) 0.79 Dissemin and reduce
(0.09 to 6.65) ation, treatment
Universit failure. Diluting
y of York, lactose-
UK. containing
Tenovus formulas may
Scotland, also have some
UK. benefits but
further trials are
required to have
confidence in
this finding.
However data
were different in
outpatients
setting.
AGE=acute gastroenteritis; NIHR=National Institute for Health Research; ORS=Oral rehydration solution.
Table 5.3. Pharmacological Therapy
Reference Intervention Randomization Allocation Blinding ITT analysis Population Main results
concealment (experimental group vs. control group)
Freedman SB, Antiemetics Ondansetron vs. placebo. All studies included in the review were RCTs 95 unique Rate of admission to hospital (during ED stay) 
2013 randomized Relative Risk and NNT: 0.40 (0.19 to 0.83),
controlled trials NNT= 17 (13-60).
(N=12478) Rate of IV rehydration (during ED stay)  Relative
87 randomized Risk and NNT: 0.41 (0.29 to 0.59),
controlled trials NNT= 5 (4-8).
included subjects < Revisit rate  ewlative risk: 0.09 (0.66 to 1.79)
18 years (N = 10 954)
DeCamp LR, Ondansetron (oral: 2-8 mg; 1.6-4 Validity assessment was undertaken using two scales and a summary score was MA (6 RCTs, n=745, Reduced risk of persistent vomiting (RR 0.45, 95% CI
2008 mg; IV: 0.15-0.3 mg/kg) vs. calculated. The two scales used were the Downs and Black checklist (maximum 1 mo-12 y with 0.33 to 0.62; NNT 5); reduced need for IV therapy (RR
placebo. score 31) and the Delphi List (maximum score 9). Validity assessment was vomiting and AGE) 0.41, 95% CI 0.28 to 0.62, NNT 5); and reduced risk of
undertaken by two independent reviewers. immediate hospital admission (RR 0.52, 95% CI 0.27
to 0.95, NNT 14). Increased diarrheal episodes (3
RCTs, data not pooled). No effect on return to care
(RR 1.34, 95% CI 0.77 to 2.35).
Carter B, Ondansetron (oral: 2-8 mg; IV: Quality of the evidence (GRADE) as assessed by the authors – low to moderate MA (7 RCTs, n=760, Increased cessation of vomiting: (oral administration:
2012 0.15-0.3 mg/kg) vs. placebo (depending on the outcome) due to design limitation (risk of bias) and/or <18 y with vomiting 4 RCTs, RR 1.44, 95% CI 1.29 to 1.61; IV
inconsistency due to possible change of effect of intervention over time and and AGE) administration: 3 RCTs, RR 2.01, 95% CI 1.49 to 2.71;
inconsistent follow up. NNT 3). Reduced need for IV therapy: (oral
administration, 4 RCTs, RR 0.41, 95% CI 0.29 to 0.59;
NNT 5). Increased number of episodes of diarrhea
(P<0.05).
Gouin S, 2012 Dimenhydrinate (oral: dosage of 1 Adequate Adequate DB No N=152 (76 cases and The prescription of oral dimenhydrinate did not
mg/kg per dose every 6 hours for 76 controls) significantly decrease the frequency of vomiting in
4 doses, with a maximum dose of children with acute gastroenteritis compared with
200 mg/day) vs placebo placebo.
Kita F, 2012 Domperidone plus ORS vs ORS Adequate N=56 (24controls) It appears that domperidone in combination with
alone ORT in the treatment of acute gastroenteritis does
not reduce vomiting in the early period.
Lehert P, Racecadotril Racecadotril (typically 1.5 mg/kg The methodological quality of each study was assessed using MA (9 RCTs, n=1384, Higher proportion of patients with recovery defined
2011 TID) vs. placebo or equivalent (in Chalmers scale (including sequence generation, allocation concealment, 1 mo- 15 y) as patients with a diarrhea duration of less than 2
particular, kaolin-pectin) adequacy of blinding and handling of incomplete outcome data). Included days (HR 2.04, 95%CI 1.85 to 2.32; P<0.001).
studies were of various methodological quality. Reduced mean stool output in inpatients (HR 0.59,
95%CI 0.51 to 0.74; P<0.001).
Reduced mean number of diarrheal stools in
outpatients (HR 0.63, 95%CI 0.51 to 0.74; P<0.001).
Dupont C, Smectite Smectite (6-12 g) vs. placebo. Adequate Unclear DB Per protocol N=602 (1-36 mo) Peru: lower 72-hour cumulative stool output
2009 analysis (P=0.032); shorter duration of diarrhea (P=0.001).
Malaysia: lower 72-hour stool output (P=0.007);
shorter duration of diarrhea (P=0.001).
Mujawar QM, Diosmectite (4.5 g/d for 5 d) Adequate Unclear Single ? N=117 (2-5 y) with Shorter time for resolution of diarrhea (P<0.001).
2012 vs. no intervention blinded AGE.
Patro B, 2008 Zinc Zinc vs. placebo or zinc in other Key criteria assessed included the adequacy of allocation concealment, blinding MA (18 RCTs, Reduced duration of diarrhea (13 RCTs, n=5643, MD -
dose or no intervention (investigators, participants, outcome assessors and data analysts), ITT analysis n=11,180 with AGE, 0.7 day; 95% CI -0.97 to -0.40).
and completeness of follow‐up. Study quality was reported to be high. <5y) Reduced the risk of diarrhea lasting >7days (8 RCTs,
n=5769, RR 0.71; 95% CI 0.53–0.96).
Increased chance of vomiting (5 RCTs, n=3156, RR
1.2; 95% CI 1.05–1.4).
Patel A, 2010 Zinc vs. placebo or no No report of the formal assessment of the risk of bias in included trials. MA (26 RCTs, Shorter duration of diarrhea (19 RCTs; n=8957;
intervention n=20,480) shortened by 19.7%; 95% CI 11.9% to 27.4%).
Increased chance of vomiting (10 RCTs; n=6779; OR
2.13; 95%CI 1.37-3.31).
No effect on stool frequency and stool output.
Lazzerini M, Zinc vs. placebo Quality of the evidence (GRADE) as assessed by the authors – very low (death; MA (24 RCTs, Reduced duration of diarrhea in children > 6 mo (MD
2012 hospitalization); low (duration of diarrhea all trials); moderate (diarrhea on day n=9128, age 1 mo- 5 -10 h; 95%CI -21.12 to 0.25).
7); high (duration of diarrhea in trials limited to children with signs of moderate y) Reduced duration of diarrhea in malnourished
malnutrition; adverse events). children (MD -27 h; 95%CI -14.7 to -39).
Allen SJ, 2010 Probiotics Probiotics vs. placebo or no The methodological quality (i.e. generation of allocation sequence, allocation MA (63 RCTs, Reduced duration of diarrhea (35 RCTs, n=4555; MD -
(as a group) intervention. concealment, blinding, and loss to follow) varied considerably. Twenty-three n=8014) 25 h; 95% CI 16 to 34); reduced risk of diarrhea
studies were considered adequate lasting ≥4 days (29 RCTs, n=2853, RR 0.41, 95% CI
for generation of the allocation sequence, 15 for concealment of allocation, 35 0.32 to 0.53).
for blinding and 45 for loss to follow up. Ten studies were adequate for all of
the four methodological quality assessment
parameters and five studies were inadequate for all four parameters.
Allen SJ, 2010 Lactobacillus GG Lactobacillus GG vs. placebo or no See above MA, 11 RCTs, Reduced duration of diarrhea (MD -26.69; 95%CI -
intervention n=2072 40.5 to -12.88), mean stool frequency on day 2 (6
RCTs, n=1335; MD -0.76, 95%CI -1.32 to -0.2), and
the risk of diarrhea lasting ≥4 days (4 RCTs, n=572; RR
0.59, 95%CI 0.40 to 0.87).
Szajewska H, Lactobacillus GG Daily doses of LGG ranging from The methodological quality of the studies (generation of randomization, MA, N= 2963 Lactobacillus GG reduces the duration of diarrhea
2013 1.2 x 108 CFU to 2 x 1012 CFU in allocation concealment, blinding, ITT analysis, and completness to follow-up) patients (1603 in the either in terms of days and hospitalization
addition to rehydration therapy vs varied. experimental group
Placebo and 1360 in
the control group)
 15 studies
Allen SJ, 2010 Saccharomyces S boulardii vs. placebo or no See above MA (10 RCTs, n=860) Reduced risk of diarrhea lasting ≥4 d (6 RCTs, n=606,
boulardii intervention RR 0.37; 95% CI 0.21 to 0.65; NNT 3, 95% CI 2-3).
Szajewska H, S boulardii vs. placebo or no The methodological quality of the trials varied. MA (9 RCTs, n=1117) Reduced duration of diarrhea (7 RCTs, n=944, MD
2009 intervention 1.08 d, 95%CI -1.64 to -0.53
Dinleyici EC, S boulardii vs. placebo or no All included trials had a number of methodological limitations; however, >80% MA (13 RCTs) Reduced duration of diarrhea (11 RCTs, n=1306; MD -
2012 intervention of the studies have follow-up and ITT analysis. Small sample sizes in some of 0.99 d (-1.4 to -0.58).
the trials. Diarrhea on day 3 (9 RCTs, n= 1128; RR 0.52; 95% CI
0.42 to 0.65)
Duration of hospitalization (n=449; MD -0.84 d (-1.14
to -0.54)
Riaz M, 2012 S boulardii vs. placebo Unclear Unclear DB No (ACA) N=108 (3-59 mo) Reduced duration of diarrhea (P=0.03)
Shorter time of appearance of first semi- formed
stool (P=0.008).
Correa NB, S boulardii vs. placebo Adequate Unclear DB No N=176 (6-48 mo) Reduced frequency of diarrhea at day 2 (P<0.01).
2011 (ACA) Reduced frequency of diarrhea at day 3 (P<0.01).
Chmielewska L. reuteri ATCC L. reuteri ATCC 5573 vs. placebo The methodological quality of the studies (generation of randomization, MA (2 RCTs, n=106) Reduced duration of diarrhea (MD -25 h; 95%CI-39.4
A, 2008 5573 allocation concealment, blinding, ITT analysis, and completeness to follow-up) to -10.9).
varied. Reduced risk of diarrhea on day 1 (RR 0.88; 95%CI 0.8
to 0.99), on day 2 (RR 0.6; 95%CI 0.4 to 0.8), on day 3
(RR 0.45; 95%CI 0.3 to 0.8), and on day 4 (RR 0.36;
95%CI 0.1 to 0.7).
Francavilla R, L. reuteri DSM L. reuteri DSM 17938 vs. placebo Adequate Unclear DB Yes N=74 (6-36 mo) Reduced duration of watery diarrhea (P<0.03).
2012 17938 Smaller number of patients with persistent diarrhea
on day 2 (P<0.01) and on day 3 (P<0.03).
Lower relapse rate (P<0.03).
Piescik-Lech LGG (6 x 109) LGG (6 x 109) plus scmectite vs Adequate Adequate DB Yes N=88 children (44 LGG plus smectite and
M, 2013 plus scmectite LGG plus Placebo treated and 44 LGG alone are equally effective for treating young
controls) aged 4 to children
60 months with AGE. Combined use of the two interventions is
not
justified.
Vandenplas Y, Synbiotics 5 probiotic strains & Adequate Adequate DB Yes N=111 (1-186 mo) Reduced duration of diarrhea [3 days (IQR 2-4) vs. 4
2011 fructooligosaccharides vs. placebo days (IQR 4-5); P<0.005].
Passariello A, L. paracasei B21060 plus Adequate Adequate DB Yes N=107 (3-36 mo) Higher rate of resolution of diarrhea at 72 hours
2012 arabinogalactan and (P=0.005).
xilooligosaccharides vs. placebo Reduced duration of diarrhea (P=0.04).
Reduced number of daily stool outputs from 48 to 72
hours after treatment (P=0.005).
Teran CG, Nitazoxanide Nitazoxanide 15 mg/kg/d for 3 Adequate Unclear SB No (ACA) N=75 (1-24 mo) Reduced duration of diarrhea (52.9±27.7 vs.
2009 days vs. placebo 74.6±26.6 h; MD -21.7 h, 95% CI -34.74 to -8.66).
Reduced duration of hospitalization (81.8±30.8 vs.
100.9±27.3; MD -19.1 h; 95% CI -33.27 to -4.93).
AGE=acute gastroenteritis; ACA=available-case-analysis; CI=confidence interval; ED=Emergency department; HR=hazard ratio; IV=intravenous; LGG=
Lactobacillus rhamnosus GG; MA=meta-analysis; MD=mean difference; OR=odds ratio; ORS=oral rehydration solution; ORT=oral rehydration treatment;
RR=risk ratio; TID= three times a day.
5.4. Anti-infective therapy

Table 5.4.1. Pathogen-based approach: Shigella gastroenteritis
Reference Study type Population Intervention Comparison Outcome

Vinh H, 2011 RCT, open-label 494 hospitalized children with Gatifloxacin 10mg/kg/d (single Ciprofloxacin 30mg/kg/d (bid), Similar duration of symptoms (95 vs 93 hs) and clinical failure rates
Allocation concealment dysentery (107 with confirmed dose), for 3 days for 3 days
shigellosis)
Christopher PR, 2010 Meta-analysis 1748 children and adults with 16 controlled trials of Placebo or comparative Appropriate antimicrobial therapy shotened the duration of Shigella
Shigella dysentery antibiotics for Shigella antibiotics dysentery
dysentery Insufficient evidence to support superior efficacy of any class of
antibiotics
Boumghar-Bourtchai L, Case series 50 children, mostly hospitalized, Identification of plasmid- Macrolide-resistant S. Sonnei in France
2008 with shigellosis, during an mediated macrolide resistance -
outbreak
Centers for Disease Report of an outbreak 43 cases of suspected shigellosis, Clinical and laboratory Plasmid-mediated azithronycin resistance (MIC>16 mcg/ml),
Control and 14 confirmed S. sonnei investigation - Single clone by PFGE
Prevention (CDC),
2012
Centers for Disease Case series 2 hospitalized children and an Descriptive antibiotic Reprt from the US of S.flexneri 2a resistant to cefriaxone and
Control and adult with clinical shigellosis resistance - ciprofloxacin
Prevention (CDC),
2010
Vrints M, 2009 Descriptive 7307 Shigella isolates (children Descriptive antibiotic Very high resistance to ampicillin and TMP-SMX
and adults) in Belgium resistance - Resistance to nalidixic acid (12.8%); no resistance to ciprofloxacin
During 1990-2007
Shiferaw B, 2012 Descriptive 1376 Shigella isolates (children Descriptive antibiotic High resistance to ampicillin and TMP-SMX
and adults) in the US resistance - Low resistance to nalidixic acid (2%) and ciprofloxacin (0.5%)
During 2000-2010
Haltalin KC, 1967 Double-blind 52 children hospitalized Ampicllin vs sulfadiazine vs Length of symptoms and Ampicillin (vs placebo) shortened the duratin of diarrhea by 45%
RCT With Shigella GE placebo Fecal excretion (3.3 d vs 6), of fever by 50% (1.3 vs 2.6) and excretion by 60% (2 vs %)
Allocation concealment
Basualdo W, 2003 Open-label 182 children with bloody Azithromycin (12 and then 6 Length of symptoms and Azithro vs cefixime: clinical success 93% vs 78%, clinical failure 2 vs 7
RCT diarrhea of whom 75 had mg/d) vs cefixime (8mg/d), Fecal excretion, clinical and children, legth of diarrhea 2.5 vs 3.9 d, bacterial eradication 93% vs
Allocation concealment shigellosis, mostly S. flexneri both for 5 d bacteriologic relapse during 59% (p<0.01, 95% CO 1.7-69.7), clinical relapse 1 child in azithro group,
1w after end of therapy bacteriologic relapse 1 vs 2 patients
Ashkenazi S, 1993 Double-blind 102 children with inflammatory Cefixime (8 mg/kg/d, bid vs T-S, Length of symptoms and Better clinical and bacteriological efficacy of cefixime, mainly because
RCT diarrhea, of whom 79 had 5d Fecal excretion 32/39 treated with T-S were resistant to it. Bacteriologic eradication by
Allocation concealment shigellosis, mostly S. sonnei cefixime was 78% (sub-optimal )
Miron D, 2004 Non-randomized 29 children with S. sonnei Azithromycin 10mg/kg for 3 d Length of symptoms and Better efficacy of azithromycin: clinical response 100% vs 65%, p<0.01,
controlled study during vs nalidixic acid 55mg/kg/d qid Fecal excretion bacterilogic response 100% vs 72%, p=0/012
outbreak for 5 d
Varsano I, 1991 Open 49 children with severe Ceftriaxone 50mg/kg/d, IV then Length of symptoms and Better efficacy of ceftriaxone: diarrhea 2.5 vs 6.8 d (p<0.005), bacterial
RCT dysentery, of whom 40 had IM vs ampicillin 100mg/kg/d, IV Fecal excretion, relapse rates eradication 100% vs 60% (p<0.001), bacteriologic relapse 0 vs 40%
shigellosis, mostly S. sonnei then PO, both for 5d (p<0.001)
Eidlitz-Marcus T, 1993 Open 40 children with shigellosis, Ceftriaxone 50mg/kg/d, IV then Length of symptoms and No difference between 2 and 5 days
RCT mostly S. sonnei IM 5d vs 2d Fecal excretion
Salam MA, 1988 Double-blind 9o children with dysentery, of Nalidixic acid 55 mg/kg/d vs Length of symptoms and Nalidixic acid and Ampicillin effective, when the isolate susceptible to
RCT whom 74 had shigellosis, mostly ampicillin 100 mg/kg/d, both Fecal excretion Ampicillin. Clinical response 81% vs 77%, Bacteriologic response 100%
S. dysenteriae and S. sonnei for 5d for both groups on d 3, but the response after 1d was better (38% vs
12%)
Bennish ML, 2006 Review of 7 studies and 378 patients with S. dysenteriae, Appropriate antibiotic therapy Rate of the HUS complication, Low risk of developing HUS with therapy( 0.0026), early antibiotics
follow up of 20 children 250 children, 128 adults fecal Stx level reduces fecal Stx levels
prospectively
Leibovitz E, 2000 Double-blind RCT 221 children with invasive Ciprofloxacin PO 20mg/kg/d Length of symptoms and No differences in the clinical or bacteriologic response. No joint
diarrhea, 73 with shigellosis bid vs IM ceftriaxone Fecal excretion problems related to cipro treatmet for 3 d
50/mg/kg, both 3d
Prado D, 1992 RCT 93 children with dysentery, of Ceftibuten 9 mg/kg/d vs T-S 10- Length of symptoms and Similar clinical and bacteriologic responses unless the pathogen was
whom 22 had shigellosis or EIEC 50mg/kg/d Fecal excretion resistant to T-S
Both bid, for 5d
DuPont HL, 2001 Double-blind 187 adults with traveler’s Rifaximin 400 mgX2/d vs Length of symptoms and Similar clinical and bacterial efficay. But: only 9 Shigella, 64 ETEC; no
RCT diarrhea, 9 with Shigella, no Ciprofloxacin 500 mgX2/d, both Fecal excretion studies in children
studt in children for 3 d
AGE=acute gastroenteritis; ED=Emergency department; EIEC=enteroinvasive E. coli; ETEC=enterotoxigenic E. coli; HUS=hemolytic-uremic syndrome;
IM=intramuscular; IV=Intravenous; LGG=Lactobacillus rhamnosus GG; ORS=Oral rehydration solution; ORT=Oral rehydration treatment; PO=Oral; Stx=Shiga
toxin; TID= three times a day; T-S=trimethoprim-sulfamethoxazole.
Table 5.4.2. Pathogen-based approach: Salmonella (non-typhoidal) gastroenteritis

Onwuezobe Systematic 12 trials identified Antibiotics vs placebo or no Clinical and bacteriologic No significant differences in length of diarrhea or fever between any antibiotic regimen and
IA, 2012 Review Including 767 patients with antibiotics responses, relapse, placebo. Antibiotics result in more negative cultures during the 1st week of treatment, but more
of RCTs Salmonella gastroenteritis, of adverse effects cases of positive cultures after 3 weeks. Relapse more frequent in those receiving antibiotics.
1980-8/2012 whom 258 were children Adverse effects more common with antibiotics
Shkalim V, Descriptive 17 children with non-typoidal Salmonella bacteremia was associated with toxic appearance and convulsions (17%) and occurred
2012 study Salmonella bacteremia during - - in children older than 3 months
1995-2010
Chiu CH, 1999 Open-label RCT 42 children with Salmonella GE Azithromycin 10mg/kg/d vs Clinical and bacteriologic Duration of diarrhea or fever not affected by antibiotics. No effects of antibiotics on fecal
Allocation cefixime 10mg/kg/d bid, both responses eradication
concealment for 5 days vs no antibiotics
Sirinavin S, Open-label RCT 265 asymptomatic carriers of Norfloxacin 400 mgx2/d vs Fecal eradication: stool Antibiotic regimens had no significant effect vs placebo on fecal eradication, and was associated
2003 Salmonella Azithromycin 500 mg/d, both cultures on days 7, 30, with development of antibiotic resistance
for 5 days, vs placebo 60, 90.
Table 5.4.3. Pathogen-based approach: Campylobacter gastroenteritis

Vukelic D, 2010 RCT 120 children (<12 y) with Single dose (20 or 30 1. Erythromycin for 5 1. Erythromycin was not better than no antibiotics
Assessor-blind Campylobacter enterocolitis mg/kg) azithromycin days 2. A single dose of azithromycin, 30 mg/kg, was superior to no antibiotics and
Allocation 2. No antibiotics to erythromycin
concealment 3. All antibiotic regimens had 100% bacteriologic cure
Ternhag A, 2007 Meta-analysis 11 double-blind RCTs Antibiotics vs no Clinical and bacteriologic Antibiotics reduced the duration of intestinal symptoms by a mean of 1.3 days
treatment or placebo outcome
Salazar-Lindo E, Double-blind 170 children 3-60 mo with Erythromycin Clinical and bacteriologic Treatment failure clinically 0% vs 42% (p<0.01), diarrhea after 2d 0% vs 64% (p<0.05),
1986 RCT acute dysentery, of whom 50mg/kg/d qid for 5 responses normal stools after 5 d 7% vs 50% (p<0.02), shorter excretion of the pathogen. Clinical
Allocation 30 had Campylobacter jejuni days vs placebo and bacteriologic efficacy documented with the early treatment, for dysenteric Campy
concealment Treatment started within 5 GE and with a dose of 50mg/kg/d
days of diarrhea
Williams MD, 1989 Open-label 20 children (>6m) and 23 Erythromycin Clinical and bacteriologic In those with Campy GE: eryhromycin was bacterilogical efficacious – fecal eradication
RCT adults with acute (<72h) 50mg/kg/d tid vs TMP- responses on d3 was 100% vs 10% (p<0.002) and on d5 100% vs 20% (p<0.001). Clinically, no
Allocation inflammatory diarrhea were SMX, both for 5 days significant effect on mean days of diarrhea, mean stools per day and mean symptom
concealment enrolled. score
21 were C. Jejuni positive
Pai CH, 1983 Open-label 27 children with confirmed Erythromycin Clinical and bacteriologic Duration of diarrhea (3.2 vs 3.8) or fever
RCT Campy GE 40mg/kg/d qid for 7 responses Bacterial shedding: 2 vs 16.8 d (p<0.05)
days vs no treatment relapse Relapse: 6.7% vs 25%
Nean diarrhea before
treatment: 5.5 vs
6.4d!!!
Ashkenazi S, 1987 Intervention Ongoing outbreak of Campy GE Erythromycin Fecal eradication, outbreak The ongoing outbreak stopped
during a DCC in a DCC, 50mg/kg/d qid course.
outbreak 22 children For 7 days
DCC=day-care center; D=day; GE=gastroenteritis.
Table 5.4.4. Pathogen-based approach: E. coli, cholera, others gastroenteritis

Kaushik JS, 2010 RCT 180 hospitalized children with confirmed Azithromycin, single 20/mg/kg Ciprofloxacin, single Azithromycin superior: clinical efficacy 95% vs 71%, bacteriologic efficacy 100% vs
Allocation cholera diarrhea dose 20mg/kg dose 96%, duration of diarrhea 55 vs 72 h and vibrio excretion 35 vs 52 h and less IV fluid
concealment needed (3491 vs 4705 ml.
Wong CS, 2012 Case-control 259 children with O157:H7 diarrhea Antibiotics No antibiotics HUS rate: 36% with antibiotics vs 12% without (p=0.001)
study
Geerdes-Fenge Case-control 24 patients with EHEC (O104:H4) diarrhea Ciprofloxacin Other or no antibiotics HUS rate: 40% with ciprofloxacin vs 89% without ciprofloxacin (p=0.043)
HF, 2013 study
Trehan I, 2009 RCT 144 ambulatory children aged 3-5 years with PO rifaximin for 7 days Placebo No beneficial effect of rifaximin, "suggesting that small-bowel bacterial over growth
Double-blind tropical enteropathy in not an important etiology in this condition
Allocation
concealment
Hu Y, 2012 Meta-analysis 4 RCTs including 502 participants PO rifaximin Placebo Rifaximin reduced significantly the rate of non-invasive E. coli (mainly ETEC) diarrhea
Safdar N, 2002 Meta-analysis 26 publications were identified; 9 fulfilled Antibiotic therapy of E. Coli Risk of developing HUS A total of 1121 patients with E. coli O157:H7 enteritis were analyzed, of whom 175
O157:H7 and the criteria for inclusion in the analysis O157:H7 and the risk of HUS developed HUS.
HUS Only one randomized, the others prospective Various antibiotics were used
cohort or retrospective case-control studies The odds ratio was 1.15 (95% CI 0.79-1/68)
Recommended a prospective large RCT
Proulx F, 1992 Open-label 47 children with E. coli O157:H7 enteritis T-S for 5 d vs no antibiotics Length of symptoms Antibiotics (vs no treatment) did not affect the resolution of clinical symptoms or
RCT Randomization 7.4 days after the onset of and bacterial eradication. The risk of HUS was 9% vs 16%
diarrhea Fecal excretion, risk of
developing HUS
Oberhelman RA, Double-blind 141 children with acute diarrhea, of whom TMP-SMX for 5 d vs placebo Length of symptoms IN children with ETEC: significant (p<0.01) improvement in the clinical symptoms with
1987 RCT 31 had enterotoxigenic E. coli and antibiotics and in bacteriological efficacy
fecal excretion
Ericsson CD, Double-blind 191 adults with travelers diarrhea were Ciprofloxacin or T-S or placebo Length of symptoms Clinical efficacy of both antibiotics: average h of diarrhea were 33, 26, and 84
1987 RCT enrolled, of whom 73 had ETEC for 5 days and (p<0.001). Bacteriologic efficacy also documented: fecal eradication rates were 100%,
Fecal excretion, relapse 100% and 71%
Adachi JA, 2003 Double-blind 217 adults with traveler’s diarrhea, of whom Azithromycin 100 mg vs Length of symptoms Similar clinical efficacy of azithromycin and levofloxacin: duration of diarrhea 22.3 vs
RCT 110 had ETEC levofloxacin 500 mgd and 21.5 h. Bacteriologic eradication 55% vs 61%
Fecal excretion
Infante RM, Double-blind Adults with traveler’s diarrhea caused by PO rifaximin vs placebo Length of symptoms Shorter duration of diarrhea with rifaximin: 22 vs 72 hours, (p=0.03)
2004 RCT EaggEC
Thoren A, 1980 Open-label 49 infants with EPEC diarrhea Mecillinam vs T-S vs placebo Length of symptoms Better clinical response with both antimicrobial agents: 79% vs 73% vs 7% (p<o.001).
RCT and Bacteriologic response: 53% for both antibiotic groups vs 0% (p<o.001).
Allocation Fecal excretion
concealment
EPEC=enteropathogenic Escherichia coli; ETEC= Enterotoxigenic Escherichia coli; HUS=hemolytic-uremic syndrome; T-S=trimethoprim-sulfamethoxazole.
Table 5.4.5. Antimicrobial therapy of parasite-induced gastroenteritis

Vandenberg O, Prospective cohort 130 children (3mo-3yr) attending a Collection of stool samples over - Our study underscores the need to rule out Cryptosporidium etiology in a
2012 study day-care center in Brussels diarrheal outbreak in a DCC. Rapid implementation of infection control
measures can most likely halt the spread of infection
Granados CE, MA (19 RCTs) 1817 patients (1441 children) with Albendazole (400 mg once daily metronidazole (250 mg to 500 Studies were generally small, with poor methods reporting. Albendazole may be
2012 giardiasis infection for five to 10 days) mg three times daily for five to of similar effectiveness to metronidazole, may have fewer side effects, and has
10 days) the advantage of a simplified regimen.
Escobedo AA, Controlled trial 166 children infected with G. tinidazole, given as a single dose nitazoxanide, given at a dose of Cure rate: G. lamblia not found in both post-treatment samples: 90.5%
2008 lamblia, with those of of 50 mg/kg. (63 completed the 7.5 mg/kg twice a day for 3 days. Tinidazole vs 78.4% Nitazoxanide (P<0.05)
study) (74 completed the study)
Canete R, Double-blind, 150 Adults patients had a Albendazole, 400 mg/daily for 5 Metronidazole 250 x3/die for 5 Cure rate: 82,6% vs 85,3 %, p>0.05 . Side effects : bitter taste, headache,
2012 randomized, confirmed symptomatic G. days (75 pts) days (75 pts) vomiting and dizziness significantly higher in the Mentronidazole group.
controlled trial duodenalis mono-infection Abdominal pain significantly higher in Albendazole group
DCC=day-care center.
Table 5.4.6 Antiviral treatment
Reference Study QoS Country In/Out Population Randomization Blinding Allocation Intervention Comparison FU ITT Outcomes Effect Effect size Comments
type Patients concealment measures measure (95% CI)
Guarino A, RCT + Italy Inpatien N=98 Appropriate Double- Not clear Single oral d Placebo 98/ Yes Mean Number 76 vs 131 Consistent evidence demonstrated
1994 ts children blinded ose of 300 98 duration of (p<0.01) that oral administration of
with acute mg/kg body diarrhea (h) immunoglobulin (300 mg/kg) may
gastroenter weight of Viral Number 114 vs 180 be beneficial for rotaviral infection
itis human excretion (h) (p<0.01) and is associated with a faster
serum Hospital stay - *reduced in recovery from acute diarrhea
immunoglob (h) treated
ulin chilren
Sarker SA, RCT + Banglad Inpatien N=85 male Appropriate Double- Appropriate Immunoglob Placebo 80/ No Stool rate Mean±SD Day 1 (P =
1998 esh ts infants and blinded ulin from 85 (grams/kg/d 0.006), Day 2
children immunized ay) (0.006) and
aged 4 to bovine Day 3 (0.02)
24 months colostrum Intake of Mean±SD 281±30 vs

with a (10 g in 20ml ORS 410±39;
history of of water in 4 (ml/kg/day) p<0.001
acute divided Stool Number 29 vs 42;
watery doses for 4 frequency p=0.007
diarrhea days) (number/da
ys 1-4)
Number of Mean±SD 1.5 vs. 2.9, P <
days 0.001
required for
RV ELISA-
negative
stool (days)
Duration of Mean±SD 72.6±38.9 vs
diarrhea 96.4±46.7;
after p=0.0016
initiation of
therapy (h)
Rahman S, RCT + Myanm Inpatien N=54 Appropriate Double- Appropriate Rotamix IgY Placebo 52/ Yes Intake of Mean±SD 699.3±111.1 Oral administration of IgY could
2012 ar ts infants and blinded four times 54 ORS (ml) vs. improve clinical outcomes (ORS
children daily for 8 919.1±171.31 intake, and duration of IV
aged consecutive , p=0.004 administration, of diarrhea, and of
between 2 days in Mean Mean 5 vs 8; p=0.03 RV clearance), even for patients
and addition to duration of with mixed (RV and non-RV)
36months rehydration intravenous enteric infections, and is a
with acute therapy fluid potentially useful adjunct to
watery administrati general supportive therapy in
diarrhea on (days) pediatric patients
and No. of Mean±SD 6.7±4.3 vs
dehydratio stools/day 10.2±8.8
n (day 2) (p=0.03)
Total Mean±SD 135.3±42.0 vs
duration of 185.5±41.7;
diarrhea p=0.01
from day of
admission
(h)
Florescu Case- + USA Inpatien N=24 - - - 25 mg/kg of Controls - - Resolution OR 65.3; p=0.008 Oral immunoglobulin treatment
DF, 2011 contr ts immunoco oral human of diarrhea has been proposed for NV
ol mpromised immunoglob Stool output Mean -22.15 vs - enteritis. Resolution of diarrhea
study patients (16 ulin seven days 10.20; and decreased stool output were
children) administere after p=0.009 observed at 7 days, but no benefit
diagnosed d every six h treatment was found for length of hospital
with NV for a total of (mL/kg/day) stay or hospital cost
gastroenter eight doses
itis in adjunct to
standard
therapy
NV=Norovirus; OR=odds ratio; ORS=Oral rehydration solution; QoS=Quality of Study; RV=Rotavirus.
Table 5.4. Nitazoxanide
Reference Intervention Randomization Allocation Blinding ITT Population Main results

concealment analysis (experimental group vs. control group)
Teran CG, Nitazoxanide 15 mg/kg/d for 3 days vs. Adequate Unclear SB No (ACA) N=75 (1-24 Reduced duration of diarrhea (52.9±27.7 vs. 74.6±26.6 h; MD -21.7 h, 95% CI -34.74
2009 placebo mo) to -8.66).
Reduced duration of hospitalization (81.8±30.8 vs. 100.9±27.3; MD -19.1 h; 95% CI -
33.27 to -4.93).
ACA=available case analysis; CI=confidence interval; MD=Median duration.
Bibliography
Abba K, Sinfield R, Hart CA, et al. Antimicrobial drugs for persistent diarrhoea of unknown or non-specific cause in children under six in low and middle
income countries: systematic review of randomized controlled trials. BMC Infect Dis 2009;9:24.
Adachi JA, Ericsson CD, Jiang ZD, et al. Azithromycin found to be comparable to levofloxacin for the treatment of US travelers with acute diarrhea acquired in
Mexico. Clin Infect Dis 2003;37:1165-71.
Akech SO, Karisa J, Nakamya P, et al. Phase II trial of isotonic fluid resuscitation in Kenyan children with severe malnutrition and hypovolaemia. BMC
Pediatr 2010;10:71.
Al Jarousha AM, El Jarou MA and El Qouqa IA. Bacterial enteropathogens and risk factors associated with childhood diarrhea. Indian J Pediatr 2011;78:165-
70.
Alam NH, Raqib R, Ashraf H, et al. L-isoleucine-supplemented oral rehydration solution in the treatment of acute diarrhoea in children: a randomized
controlled trial. J Health Popul Nutr 2011;29:183-90.
Allen SJ, Martinez EG, Gregorio GV, et al. Probiotics for treating acute infectious diarrhoea. Cochrane Database Syst Rev 2010;CD003048.
Allison GM, Rogers KA, Borad A, et al. Antibody responses to the immunodominant Cryptosporidium gp15 antigen and gp15 polymorphisms in a case-control
study of cryptosporidiosis in children in Bangladesh. Am J Trop Med Hyg 2011;85:97-104.
Ansaldi F, Lai P, Valle L, et al. Burden of rotavirus-associated and non-rotavirus-associated diarrhea among nonhospitalized individuals in central Italy: a 1-
year sentinel-based epidemiological and virological surveillance. Clin Infect Dis 2008;46:e51-5.
Ashkenazi S, Danziger Y, Varsano Y, et al. Treatment of Campylobacter gastroenteritis. Arch Dis Child 1987;62:84-5.
Ashkenazi S, Amir J, Waisman Y, et al. A randomized, double-blind study comparing cefixime and trimethoprim-sulfamethoxazole in the treatment of
childhood shigellosis. J Pediatr 1993;123:817-21.
Bailey B, Gravel J, Goldman RD, et al. External validation of the clinical dehydration scale for children with acute gastroenteritis. Acad Emerg Med
2010;17:583-8.
Bandin F, Kwon T, Linas MD, et al. Cryptosporidiosis in paediatric renal transplantation. Pediatr Nephrol 2009;24:2245-55.
Basualdo W and Arbo A. Randomized comparison of azithromycin versus cefixime for treatment of shigellosis in children. Pediatr Infect Dis J 2003;22:374-7.
Bennish ML, Khan WA, Begum M, et al. Low risk of hemolytic uremic syndrome after early effective antimicrobial therapy for Shigella dysenteriae type 1
infection in Bangladesh. Clin Infect Dis 2006;42:356-62.
Bhutta ZA, Nelson EA, Lee WS, et al. Recent advances and evidence gaps in persistent diarrhea. J Pediatr Gastroenterol Nutr 2008;47:260-5.
Bok K and Green KY. Norovirus gastroenteritis in immunocompromised patients. N Engl J Med 2012;367:2126-32.
Boumghar-Bourtchai L, Mariani-Kurkdjian P, Bingen E, et al. Macrolide-resistant Shigella sonnei. Emerg Infect Dis 2008;14:1297-9.
Callery P, Kyle RG, Campbell M, et al. Readmission in children's emergency care: an analysis of hospital episode statistics. Arch Dis Child 2010;95:341-6.
Canete R, Rodriguez P, Mesa L, et al. Albendazole versus metronidazole in the treatment of adult giardiasis: a randomized, double-blind, clinical trial. Curr
Med Res Opin 2012;28:149-54.
Carter B and Fedorowicz Z. Antiemetic treatment for acute gastroenteritis in children: an updated Cochrane systematic review with meta-analysis and mixed
treatment comparison in a Bayesian framework. BMJ Open 2012;2:
Centers for Disease Control and Prevention (CDC). Notes from the field: emergence of Shigella flexneri 2a resistant to ceftriaxone and ciprofloxacin --- South
Carolina. MMWR Morb Mortal Wkly Rep 2010;59:1619.
Centers for Disease Control and Prevention (CDC). Notes from the field: Outbreak of infections caused by Shigella sonnei with decreased susceptibility to
azithromycin--Los Angeles, California. MMWR Morb Mortal Wkly Rep 2012;62:171.
Chan CM, Chan CW, Ma CK, et al. Norovirus as cause of benign convulsion associated with gastro-enteritis. J Paediatr Child Health 2011;47:373-7.
Chen CC, Chang CJ, Lin TY, et al. Usefulness of fecal lactoferrin in predicting and monitoring the clinical severity of infectious diarrhea. World J
Gastroenterol 2011;17:4218-24.
Chen L, Kim Y and Santucci KA. Use of ultrasound measurement of the inferior vena cava diameter as an objective tool in the assessment of children with
clinical dehydration. Acad Emerg Med 2007;14:841-5.
Chen L, Hsiao A, Langhan M, et al. Use of bedside ultrasound to assess degree of dehydration in children with gastroenteritis. Acad Emerg Med 2010;17:1042-
7.
Chen SM, Ku MS, Lee MY, et al. Diagnostic performance of serum interleukin-6 and interleukin-10 levels and clinical predictors in children with rotavirus and
norovirus gastroenteritis. Cytokine 2012;59:299-304.
Chisti MJ, Pietroni MA, Smith JH, et al. Predictors of death in under-five children with diarrhoea admitted to a critical care ward in an urban hospital in
Bangladesh. Acta Paediatr 2011;100:e275-9.
Chiu CH, Lin TY and Ou JT. A clinical trial comparing oral azithromycin, cefixime and no antibiotics in the treatment of acute uncomplicated Salmonella
enteritis in children. J Paediatr Child Health 1999;35:372-4.
Chmielewska A, Ruszczyński M and Szajewska H. Lactobacillus reuteri strain ATCC 55730 for the treatment of acute infectious diarrhoea in children: a meta-
analysis of randomized controlled trials. Pediatria Współczesna. Gastroenterologia, Hepatologia i Żywienie Dziecka 2008;10:33-7.
Christopher PR, David KV, John SM, et al. Antibiotic therapy for Shigella dysentery. Cochrane Database Syst Rev 2010;CD006784.
Correa NB, Penna FJ, Lima FM, et al. Treatment of acute diarrhea with Saccharomyces boulardii in infants. J Pediatr Gastroenterol Nutr 2011;53:497-501.
Das SK, Faruque AS, Chisti MJ, et al. Changing trend of persistent diarrhoea in young children over two decades: observations from a large diarrhoeal disease
hospital in Bangladesh. Acta Paediatr 2012;101:e452-7.
Day TG, Jackson C and Bryant PA. Cluster of neurological manifestations of rotavirus infection in children. BMJ Case Rep 2012;2012:20.
DeCamp LR, Byerley JS, Doshi N, et al. Use of antiemetic agents in acute gastroenteritis: a systematic review and meta-analysis. Arch Pediatr Adolesc Med
2008;162:858-65.
Diez-Gandia A, Ajenjo MA, Navalon AB, et al. [Palatability of oral rehydration solutions (ORS) in healthy 6 to 9 year-old children. A multicentre, randomised
single blind clinical trial]. An Pediatr (Barc) 2010;72:111-5.
Dinleyici EC, Eren M, Ozen M, et al. Effectiveness and safety of Saccharomyces boulardii for acute infectious diarrhea. Expert Opin Biol Ther 2012;12:395-
410.
Dunkelmann L, Bucher BS, Tschumi S, et al. Estimation of dehydration using bioelectric impedance in children with gastroenteritis. Acta Paediatr
2012;101:e479-81.
Dupont C, Foo JL, Garnier P, et al. Oral diosmectite reduces stool output and diarrhea duration in children with acute watery diarrhea. Clin Gastroenterol
Hepatol 2009;7:456-62.
Dupont C and Vernisse B. Anti-diarrheal effects of diosmectite in the treatment of acute diarrhea in children: a review. Paediatr Drugs 2009;11:89-99.
DuPont HL, Jiang ZD, Ericsson CD, et al. Rifaximin versus ciprofloxacin for the treatment of traveler's diarrhea: a randomized, double-blind clinical trial. Clin
Infect Dis 2001;33:1807-15.
Eidlitz-Marcus T, Cohen YH, Nussinovitch M, et al. Comparative efficacy of two- and five-day courses of ceftriaxone for treatment of severe shigellosis in
children. J Pediatr 1993;123:822-4.
El-Bayoumi MA, Abdelkader AM, El-Assmy MM, et al. Normal saline is a safe initial rehydration fluid in children with diarrhea-related hypernatremia. Eur J
Pediatr 2012;171:383-8.
Enright K, Beattie T and Taheri S. Use of a hand-held bladder ultrasound scanner in the assessment of dehydration and monitoring response to treatment in a
paediatric emergency department. Emerg Med J 2010;27:731-3.
Ericsson CD, Johnson PC, Dupont HL, et al. Ciprofloxacin or trimethoprim-sulfamethoxazole as initial therapy for travelers' diarrhea. A placebo-controlled,
randomized trial. Ann Intern Med 1987;106:216-20.
Escobedo AA, Alvarez G, Gonzalez ME, et al. The treatment of giardiasis in children: single-dose tinidazole compared with 3 days of nitazoxanide. Ann Trop
Med Parasitol 2008;102:199-207.
Esteban Carretero J, Durban Reguera F, Lopez-Argueta Alvarez S, et al. A comparative analysis of response to vs. ORS + gelatin tannate pediatric patients with
acute diarrhea. Rev Esp Enferm Dig 2009;101:41-8.
Fasheh Youssef W, Pino Ramirez R, Campistol Plana J, et al. Benign afebrile convulsions in the course of mild acute gastroenteritis: a study of 28 patients and
a literature review. Pediatr Emerg Care 2011;27:1062-4.
Florescu DF, Hermsen ED, Kwon JY, et al. Is there a role for oral human immunoglobulin in the treatment for norovirus enteritis in immunocompromised
patients? Pediatr Transplant 2011;15:718-21.
Francavilla R, Lionetti E, Castellaneta S, et al. Randomised clinical trial: Lactobacillus reuteri DSM 17938 vs. placebo in children with acute diarrhoea--a
double-blind study. Aliment Pharmacol Ther 2012;36:363-9.
Freedman SB, Gouin S, Bhatt M, et al. Prospective assessment of practice pattern variations in the treatment of pediatric gastroenteritis. Pediatrics
2011;127:e287-95.
Freedman SB, Parkin PC, Willan AR, et al. Rapid versus standard intravenous rehydration in paediatric gastroenteritis: pragmatic blinded randomised clinical
trial. BMJ 2011;343:d6976.
Freedman SB, Keating LE, Rumatir M, et al. Health care provider and caregiver preferences regarding nasogastric and intravenous rehydration. Pediatrics
2012;130:e1504-11.
Freedman SB, Ali S, Oleszczuk M, et al. Treatment of acute gastroenteritis in children: an overview of systematic reviews of interventions commonly used in
developed countries. Evid Based Child Health 2013;8:1123-37.
Freedman SB and Geary DF. Bolus fluid therapy and sodium homeostasis in paediatric gastroenteritis. J Paediatr Child Health 2013;49:215-22.
Friedman JN, Goldman RD, Srivastava R, et al. Development of a clinical dehydration scale for use in children between 1 and 36 months of age. J Pediatr
2004;145:201-7.
Friesema IH, de Boer RF, Duizer E, et al. Etiology of acute gastroenteritis in children requiring hospitalization in the Netherlands. Eur J Clin Microbiol Infect
Dis 2012;31:405-15.
Garcia-Basteiro AL, Bosch A, Sicuri E, et al. Hospitalizations due to rotavirus gastroenteritis in Catalonia, Spain, 2003-2008. BMC Res Notes 2011;4:429.
Geerdes-Fenge HF, Lobermann M, Nurnberg M, et al. Ciprofloxacin reduces the risk of hemolytic uremic syndrome in patients with Escherichia coli O104:H4-
associated diarrhea. Infection 2013;41:669-73.
Ghorashi Z, Nezami N, Soltani-Ahari H, et al. Convulsion following gastroenteritis in children without severe electrolyte imbalance. Turk J Pediatr
2010;52:301-5.
Gimenez-Sanchez F, Delgado-Rubio A, Martinon-Torres F, et al. Multicenter prospective study analysing the role of rotavirus on acute gastroenteritis in Spain.
Acta Paediatr 2010;99:738-42.
Gleizes O, Desselberger U, Tatochenko V, et al. Nosocomial rotavirus infection in European countries: a review of the epidemiology, severity and economic
burden of hospital-acquired rotavirus disease. Pediatr Infect Dis J 2006;25:S12-21.
Goldman RD, Friedman JN and Parkin PC. Validation of the clinical dehydration scale for children with acute gastroenteritis. Pediatrics 2008;122:545-9.
Gouin S, Vo TT, Roy M, et al. Oral dimenhydrinate versus placebo in children with gastroenteritis: a randomized controlled trial. Pediatrics 2012;129:1050-5.
Granados CE, Reveiz L, Uribe LG, et al. Drugs for treating giardiasis. Cochrane Database Syst Rev 2012;12:CD007787.
Gravel J, Manzano S, Guimont C, et al. [Multicenter validation of the clinical dehydration scale for children]. Arch Pediatr 2010;17:1645-51.
Gregorio GV, Gonzales ML, Dans LF, et al. Polymer-based oral rehydration solution for treating acute watery diarrhoea. Cochrane Database Syst Rev
2009;CD006519.
Gregorio GV, Dans LF and Silvestre MA. Early versus Delayed Refeeding for Children with Acute Diarrhoea. Cochrane Database Syst Rev 2011;CD007296.
Grimprel E, Garbarg-Chenon A, Pircon JY, et al. Surveillance to estimate the burden of rotavirus gastroenteritis in children aged less than 3 years attending day
care centers in Paris, France. Hum Vaccin 2010;6:399-406.
Guarino A, Canani RB, Russo S, et al. Oral immunoglobulins for treatment of acute rotaviral gastroenteritis. Pediatrics 1994;93:12-6.
Haltalin KC, Nelson JD, Ring R, 3rd, et al. Double-blind treatment study of shigellosis comparing ampicillin, sulfadiazine, and placebo. J Pediatr 1967;70:970-
81.
Han JJ, Yim HE, Lee JH, et al. Albumin versus normal saline for dehydrated term infants with metabolic acidosis due to acute diarrhea. J Perinatol
2009;29:444-7.
Hanna M and Saberi MS. Incidence of hyponatremia in children with gastroenteritis treated with hypotonic intravenous fluids. Pediatr Nephrol 2010;25:1471-
5.
Hayajneh WA, Jdaitawi H, Al Shurman A, et al. Comparison of clinical associations and laboratory abnormalities in children with moderate and severe
dehydration. J Pediatr Gastroenterol Nutr 2010;50:290-4.
Henke-Gendo C, Harste G, Juergens-Saathoff B, et al. New real-time PCR detects prolonged norovirus excretion in highly immunosuppressed patients and
children. J Clin Microbiol 2009;47:2855-62.
Hidayat S, Srie Enggar KD, Pardede N, et al. Nasogastric drip rehydration therapy in acute diarrhea with severe dehydration. Paediatr Indones 1988;28:79-84.
Hoorn EJ, Geary D, Robb M, et al. Acute hyponatremia related to intravenous fluid administration in hospitalized children: an observational study. Pediatrics
2004;113:1279-84.
Hu Y, Ren J, Zhan M, et al. Efficacy of rifaximin in prevention of travelers' diarrhea: a meta-analysis of randomized, double-blind, placebo-controlled trials. J
Travel Med 2012;19:352-6.
Idris NS, Dwipoerwantoro PG, Kurniawan A, et al. Intestinal parasitic infection of immunocompromised children with diarrhoea: clinical profile and
therapeutic response. J Infect Dev Ctries 2010;4:309-17.
Infante RM, Ericsson CD, Jiang ZD, et al. Enteroaggregative Escherichia coli diarrhea in travelers: response to rifaximin therapy. Clin Gastroenterol Hepatol
2004;2:135-8.
Kaiser P, Borte M, Zimmer KP, et al. Complications in hospitalized children with acute gastroenteritis caused by rotavirus: a retrospective analysis. Eur J
Pediatr 2012;171:337-45.
Kaushik JS, Gupta P, Faridi MM, et al. Single dose azithromycin versus ciprofloxacin for cholera in children: a randomized controlled trial. Indian Pediatr
2010;47:309-15.
Kinlin LM and Freedman SB. Evaluation of a clinical dehydration scale in children requiring intravenous rehydration. Pediatrics 2012;129:e1211-9.
Kita F, Hinotsu S, Yorifuji T, et al. Domperidone With ORT in the Treatment of Pediatric Acute Gastroenteritis in Japan: A Multicenter, Randomized
Controlled Trial. Asia Pac J Public Health 2012;
Korczowski B and Szybist W. Serum procalcitonin and C-reactive protein in children with diarrhoea of various aetiologies. Acta Paediatr 2004;93:169-73.
Kotch JB, Isbell P, Weber DJ, et al. Hand-washing and diapering equipment reduces disease among children in out-of-home child care centers. Pediatrics
2007;120:e29-36.
Kyle RG, Kukanova M, Campbell M, et al. Childhood disadvantage and emergency admission rates for common presentations in London: an exploratory
analysis. Arch Dis Child 2011;96:221-6.
Lazzerini M and Ronfani L. Oral zinc for treating diarrhoea in children. Cochrane Database Syst Rev 2012;6:CD005436.
Lehert P, Cheron G, Calatayud GA, et al. Racecadotril for childhood gastroenteritis: an individual patient data meta-analysis. Dig Liver Dis 2011;43:707-13.
Leibovitz E, Janco J, Piglansky L, et al. Oral ciprofloxacin vs. intramuscular ceftriaxone as empiric treatment of acute invasive diarrhea in children. Pediatr
Infect Dis J 2000;19:1060-7.
Levine AC, Shah SP, Umulisa I, et al. Ultrasound assessment of severe dehydration in children with diarrhea and vomiting. Acad Emerg Med 2010;17:1035-41.
Levy JA and Bachur RG. Intravenous dextrose during outpatient rehydration in pediatric gastroenteritis. Acad Emerg Med 2007;14:324-30.
Lorrot M, Bon F, El Hajje MJ, et al. Epidemiology and clinical features of gastroenteritis in hospitalised children: prospective survey during a 2-year period in
a Parisian hospital, France. Eur J Clin Microbiol Infect Dis 2011;30:361-8.
Macgillivray S, Fahey T and McGuire W. Lactose avoidance for young children with acute diarrhoea. Cochrane Database Syst Rev 2013;10:CD005433.
Manger MS, Taneja S, Strand TA, et al. Poor folate status predicts persistent diarrhea in 6- to 30-month-old north Indian children. J Nutr 2011;141:2226-32.
Marcus N, Mor M, Amir L, et al. The quick-read C-reactive protein test for the prediction of bacterial gastroenteritis in the pediatric emergency department.
Pediatr Emerg Care 2007;23:634-7.
Miron D, Torem M, Merom R, et al. Azithromycin as an alternative to nalidixic acid in the therapy of childhood shigellosis. Pediatr Infect Dis J 2004;23:367-8.
Moineau G and Newman J. Rapid intravenous rehydration in the pediatric emergency department. Pediatr Emerg Care 1990;6:186-8.
Moore SR, Lima NL, Soares AM, et al. Prolonged episodes of acute diarrhea reduce growth and increase risk of persistent diarrhea in children.
Gastroenterology 2010;139:1156-64.
Mor SM, Tumwine JK, Naumova EN, et al. Microsporidiosis and malnutrition in children with persistent diarrhea, Uganda. Emerg Infect Dis 2009;15:49-52.
Morales E, Garcia-Esteban R, Guxens M, et al. Effects of prolonged breastfeeding and colostrum fatty acids on allergic manifestations and infections in
infancy. Clin Exp Allergy 2012;42:918-28.
Morrow AL, Ruiz-Palacios GM, Jiang X, et al. Human-milk glycans that inhibit pathogen binding protect breast-feeding infants against infectious diarrhea. J
Nutr 2005;135:1304-7.
Moyo SJ, Maselle SY, Matee MI, et al. Identification of diarrheagenic Escherichia coli isolated from infants and children in Dar es Salaam, Tanzania. BMC
Infect Dis 2007;7:92.
Mrukowicz JZ, Krobicka B, Duplaga M, et al. Epidemiology and impact of rotavirus diarrhoea in Poland. Acta Paediatr Suppl 1999;88:53-60.
Muhsen K, Shulman L, Rubinstein U, et al. Incidence, characteristics, and economic burden of rotavirus gastroenteritis associated with hospitalization of israeli
children <5 years of age, 2007-2008. J Infect Dis 2009;200 Suppl 1:S254-63.
Mujawar QM, Naganoor R, Ali MD, et al. Efficacy of dioctahedral smectite in acute watery diarrhea in Indian children: a randomized clinical trial. J Trop
Pediatr 2012;58:63-7.
Mukhopadhyay C, Wilson G, Pradhan D, et al. Intestinal protozoal infestation profile in persistent diarrhea in children below age 5 years in western Nepal.
Southeast Asian J Trop Med Public Health 2007;38:13-9.
Nager AL and Wang VJ. Comparison of ultrarapid and rapid intravenous hydration in pediatric patients with dehydration. Am J Emerg Med 2010;28:123-9.
Narkeviciute I and Tamusauskaite I. Peculiarities of norovirus and rotavirus infections in hospitalised young children. J Pediatr Gastroenterol Nutr
2008;46:289-92.
Neville KA, Verge CF, Rosenberg AR, et al. Isotonic is better than hypotonic saline for intravenous rehydration of children with gastroenteritis: a prospective
randomised study. Arch Dis Child 2006;91:226-32.
Nylund CM, Goudie A, Garza JM, et al. Clostridium difficile infection in hospitalized children in the United States. Arch Pediatr Adolesc Med 2011;165:451-7.
Oberhelman RA, Javier de la Cabada F, Vasquez Garibay E, et al. Efficacy of trimethoprim-sulfamethoxazole in treatment of acute diarrhea in a Mexican
pediatric population. J Pediatr 1987;110:960-5.
Ochoa TJ, Ecker L, Barletta F, et al. Age-related susceptibility to infection with diarrheagenic Escherichia coli among infants from Periurban areas in Lima,
Peru. Clin Infect Dis 2009;49:1694-702.
Ogilvie I, Khoury H, Goetghebeur MM, et al. Burden of community-acquired and nosocomial rotavirus gastroenteritis in the pediatric population of Western
Europe: a scoping review. BMC Infect Dis 2012;12:62.
Oldak E, Sulik A, Rozkiewicz D, et al. Norovirus infections in children under 5 years of age hospitalized due to the acute viral gastroenteritis in northeastern
Poland. Eur J Clin Microbiol Infect Dis 2012;31:417-22.
Onwuezobe IA, Oshun PO and Odigwe CC. Antimicrobials for treating symptomatic non-typhoidal Salmonella infection. Cochrane Database Syst Rev
2012;11:CD001167.
Opintan JA, Newman MJ, Ayeh-Kumi PF, et al. Pediatric diarrhea in southern Ghana: etiology and association with intestinal inflammation and malnutrition.
Am J Trop Med Hyg 2010;83:936-43.
Pai CH, Gillis F, Tuomanen E, et al. Erythromycin in treatment of Campylobacter enteritis in children. Am J Dis Child 1983;137:286-8.
Parkin PC, Macarthur C, Khambalia A, et al. Clinical and laboratory assessment of dehydration severity in children with acute gastroenteritis. Clin Pediatr
(Phila) 2010;49:235-9.
Pascarella F, Martinelli M, Miele E, et al. Impact of Clostridium difficile infection on pediatric inflammatory bowel disease. J Pediatr 2009;154:854-8.
Passariello A, Terrin G, De Marco G, et al. Efficacy of a new hypotonic oral rehydration solution containing zinc and prebiotics in the treatment of childhood
acute diarrhea: a randomized controlled trial. J Pediatr 2011;158:288-92 e1.
Passariello A, Terrin G, Cecere G, et al. Randomised clinical trial: efficacy of a new synbiotic formulation containing Lactobacillus paracasei B21060 plus
arabinogalactan and xilooligosaccharides in children with acute diarrhoea. Aliment Pharmacol Ther 2012;35:782-8.
Patel A, Mamtani M, Dibley MJ, et al. Therapeutic value of zinc supplementation in acute and persistent diarrhea: a systematic review. PLoS One
2010;5:e10386.
Patel B, Kennebeck SS, Caviness AC, et al. Use of a discharge facilitator improves recall of emergency department discharge instructions for acute
gastroenteritis. Pediatr Emerg Care 2009;25:558-64.
Pathela P, Zahid Hasan K, Roy E, et al. Diarrheal illness in a cohort of children 0-2 years of age in rural Bangladesh: I. Incidence and risk factors. Acta
Paediatr 2006;95:430-7.
Patro B, Golicki D and Szajewska H. Meta-analysis: zinc supplementation for acute gastroenteritis in children. Aliment Pharmacol Ther 2008;28:713-23.
Payne DC, Staat MA, Edwards KM, et al. Active, population-based surveillance for severe rotavirus gastroenteritis in children in the United States. Pediatrics
2008;122:1235-43.
Pereira AL, Ferraz LR, Silva RS, et al. Enteroaggregative Escherichia coli virulence markers: positive association with distinct clinical characteristics and
segregation into 3 enteropathogenic E. coli serogroups. J Infect Dis 2007;195:366-74.
Phin SJ, McCaskill ME, Browne GJ, et al. Clinical pathway using rapid rehydration for children with gastroenteritis. J Paediatr Child Health 2003;39:343-8.
Piescik-Lech M, Szymanski H and Szajewska H. Efficacy and safety of a new apple-flavoured oral rehydration solution in children with acute gastroenteritis: a
double-blind randomized controlled trial. Acta Paediatr 2012;101:e458-64.
Piescik-Lech M, Urbanska M and Szajewska H. Lactobacillus GG (LGG) and smectite versus LGG alone for acute gastroenteritis: a double-blind, randomized
controlled trial. Eur J Pediatr 2013;172:247-53.
Pignatelli S, Simpore J, Ruggieri M, et al. Effectiveness of forced rehydration and early re-feeding in the treatment of acute diarrhoea in a tropical area.
Minerva Pediatr 2000;52:357-66.
Plaisier A, Maingay-de Groof F, Mast-Harwig R, et al. Plasma water as a diagnostic tool in the assessment of dehydration in children with acute gastroenteritis.
Eur J Pediatr 2010;169:883-6.
Pockett RD, Adlard N, Carroll S, et al. Paediatric hospital admissions for rotavirus gastroenteritis and infectious gastroenteritis of all causes in England: an
analysis of correlation with deprivation. Curr Med Res Opin 2011;27:777-84.
Powell CV, Priestley SJ, Young S, et al. Randomized clinical trial of rapid versus 24-hour rehydration for children with acute gastroenteritis. Pediatrics
2011;128:e771-8.
Prado D, Lopez E, Liu H, et al. Ceftibuten and trimethoprim-sulfamethoxazole for treatment of Shigella and enteroinvasive Escherichia coli disease. Pediatr
Infect Dis J 1992;11:644-7.
Pringle K, Shah SP, Umulisa I, et al. Comparing the accuracy of the three popular clinical dehydration scales in children with diarrhea. Int J Emerg Med
2011;4:58.
Proulx F, Turgeon JP, Delage G, et al. Randomized, controlled trial of antibiotic therapy for Escherichia coli O157:H7 enteritis. J Pediatr 1992;121:299-303.
Pruvost I, Dubos F, Chazard E, et al. The value of body weight measurement to assess dehydration in children. PLoS One 2013;8:e55063.
Rabbani GH, Ahmed S, Hossain I, et al. Green banana reduces clinical severity of childhood shigellosis: a double-blind, randomized, controlled clinical trial.
Pediatr Infect Dis J 2009;28:420-5.
Rahman S, Higo-Moriguchi K, Htun KW, et al. Randomized placebo-controlled clinical trial of immunoglobulin Y as adjunct to standard supportive therapy
for rotavirus-associated diarrhea among pediatric patients. Vaccine 2012;30:4661-9.
Rautenberg TA, Zerwes U, Foerster D, et al. Evaluating the cost utility of racecadotril for the treatment of acute watery diarrhea in children: the RAWD model.
Clinicoecon Outcomes Res 2012;4:109-16.
Reid SR and Bonadio WA. Outpatient rapid intravenous rehydration to correct dehydration and resolve vomiting in children with acute gastroenteritis. Ann
Emerg Med 1996;28:318-23.
Riaz M, Alam S, Malik A, et al. Efficacy and safety of Saccharomyces boulardii in acute childhood diarrhea: a double blind randomised controlled trial. Indian
J Pediatr 2012;79:478-82.
Rimoldi SG, Stefani F, Pagani C, et al. Epidemiological and clinical characteristics of pediatric gastroenteritis associated with new viral agents. Arch Virol
2011;156:1583-9.
Rivera FP, Ochoa TJ, Maves RC, et al. Genotypic and phenotypic characterization of enterotoxigenic Escherichia coli strains isolated from Peruvian children. J
Clin Microbiol 2010;48:3198-203.
Robertson G, Carrihill M, Hatherill M, et al. Relationship between fluid management, changes in serum sodium and outcome in hypernatraemia associated with
gastroenteritis. J Paediatr Child Health 2007;43:291-6.
Roland D, Clarke C, Borland ML, et al. Does a standardised scoring system of clinical signs reduce variability between doctors' assessments of the potentially
dehydrated child? J Paediatr Child Health 2010;46:103-7.
Ruuska T and Vesikari T. Rotavirus disease in Finnish children: use of numerical scores for clinical severity of diarrhoeal episodes. Scand J Infect Dis
1990;22:259-67.
Saba TG, Fairbairn J, Houghton F, et al. A randomized controlled trial of isotonic versus hypotonic maintenance intravenous fluids in hospitalized children.
BMC Pediatr 2011;11:82.
Safdar N, Said A, Gangnon RE, et al. Risk of hemolytic uremic syndrome after antibiotic treatment of Escherichia coli O157:H7 enteritis: a meta-analysis.
Jama 2002;288:996-1001.
Salam MA and Bennish ML. Therapy for shigellosis. I. Randomized, double-blind trial of nalidixic acid in childhood shigellosis. J Pediatr 1988;113:901-7.
Salazar-Lindo E, Sack RB, Chea-Woo E, et al. Early treatment with erythromycin of Campylobacter jejuni-associated dysentery in children. J Pediatr
1986;109:355-60.
Sandora TJ, Taveras EM, Shih MC, et al. A randomized, controlled trial of a multifaceted intervention including alcohol-based hand sanitizer and hand-hygiene
education to reduce illness transmission in the home. Pediatrics 2005;116:587-94.
Saneian H, Yaghini O, Modaresi M, et al. Lactose-free compared with lactose-containing formula in dietary management of acute childhood diarrhea. Iran J
Pediatr 2012;22:82-6.
Santucci KA, Anderson AC, Lewander WJ, et al. Frozen oral hydration as an alternative to conventional enteral fluids. Arch Pediatr Adolesc Med
1998;152:142-6.
Sarker SA, Casswall TH, Mahalanabis D, et al. Successful treatment of rotavirus diarrhea in children with immunoglobulin from immunized bovine colostrum.
Pediatr Infect Dis J 1998;17:1149-54.
Schnadower D, Tarr PI, Gorelick MH, et al. Validation of the Modified Vesikari Score in Children with Gastroenteritis in 5 U.S. Emergency Departments. J
Pediatr Gastroenterol Nutr 2013;57:514-9.
Shai S, Perez-Becker R, von Konig CH, et al. Rotavirus disease in Germany--a prospective survey of very severe cases. Pediatr Infect Dis J 2013;32:e62-7.
Sharifi J, Ghavami F, Nowrouzi Z, et al. Oral versus intravenous rehydration therapy in severe gastroenteritis. Arch Dis Child 1985;60:856-60.
Shavit I, Brant R, Nijssen-Jordan C, et al. A novel imaging technique to measure capillary-refill time: improving diagnostic accuracy for dehydration in young
children with gastroenteritis. Pediatrics 2006;118:2402-8.
Shiferaw B, Solghan S, Palmer A, et al. Antimicrobial susceptibility patterns of Shigella isolates in Foodborne Diseases Active Surveillance Network
(FoodNet) sites, 2000-2010. Clin Infect Dis 2012;54 Suppl 5:S458-63.
Shkalim V, Amir A, Samra Z, et al. Characteristics of non-typhi Salmonella gastroenteritis associated with bacteremia in infants and young children. Infection
2012;40:285-9.
Sirinavin S, Thavornnunth J, Sakchainanont B, et al. Norfloxacin and azithromycin for treatment of nontyphoidal salmonella carriers. Clin Infect Dis
2003;37:685-91.
Spandorfer PR, Alessandrini EA, Joffe MD, et al. Oral versus intravenous rehydration of moderately dehydrated children: a randomized, controlled trial.
Pediatrics 2005;115:295-301.
Steiner MJ, Nager AL and Wang VJ. Urine specific gravity and other urinary indices: inaccurate tests for dehydration. Pediatr Emerg Care 2007;23:298-303.
Strand TA, Sharma PR, Gjessing HK, et al. Risk factors for extended duration of acute diarrhea in young children. PLoS One 2012;7:e36436.
Sugata K, Taniguchi K, Yui A, et al. Analysis of rotavirus antigenemia in hematopoietic stem cell transplant recipients. Transpl Infect Dis 2012;14:49-56.
Sutra S, Kosuwon P, Chirawatkul A, et al. Burden of acute, persistent and chronic diarrhea, Thailand, 2010. J Med Assoc Thai 2012;95 Suppl 7:S97-107.
Sykora J, Siala K, Huml M, et al. Evaluation of faecal calprotectin as a valuable non-invasive marker in distinguishing gut pathogens in young children with
acute gastroenteritis. Acta Paediatr 2010;99:1389-95.
Szajewska H and Skorka A. Saccharomyces boulardii for treating acute gastroenteritis in children: updated meta-analysis of randomized controlled trials.
Aliment Pharmacol Ther 2009;30:960-1.
Szajewska H, Skorka A, Ruszczynski M, et al. Meta-analysis: Lactobacillus GG for treating acute gastroenteritis in children--updated analysis of randomised
controlled trials. Aliment Pharmacol Ther 2013;38:467-76.
Teran CG, Teran-Escalera CN and Villarroel P. Nitazoxanide vs. probiotics for the treatment of acute rotavirus diarrhea in children: a randomized, single-blind,
controlled trial in Bolivian children. Int J Infect Dis 2009;13:518-23.
Ternhag A, Asikainen T, Giesecke J, et al. A meta-analysis on the effects of antibiotic treatment on duration of symptoms caused by infection with
Campylobacter species. Clin Infect Dis 2007;44:696-700.
Thoren A, Wolde-Mariam T, Stintzing G, et al. Antibiotics in the treatment of gastroenteritis caused by enteropathogenic Escherichia coli. J Infect Dis
1980;141:27-31.
Trehan I, Shulman RJ, Ou CN, et al. A randomized, double-blind, placebo-controlled trial of rifaximin, a nonabsorbable antibiotic, in the treatment of tropical
enteropathy. Am J Gastroenterol 2009;104:2326-33.
Umamaheswari B, Biswal N, Adhisivam B, et al. Persistent diarrhea: risk factors and outcome. Indian J Pediatr 2010;77:885-8.
Valentini D, Vittucci AC, Grandin A, et al. Coinfection in acute gastroenteritis predicts a more severe clinical course in children. Eur J Clin Microbiol Infect
Dis 2013;32:909-15.
van den Berg J and Berger MY. Guidelines on acute gastroenteritis in children: a critical appraisal of their quality and applicability in primary care. BMC Fam
Pract 2011;12:134.
Vandenberg O, Robberecht F, Dauby N, et al. Management of a Cryptosporidium hominis outbreak in a day-care center. Pediatr Infect Dis J 2012;31:10-5.
Vandenplas Y and De Hert SG. Randomised clinical trial: the synbiotic food supplement Probiotical vs. placebo for acute gastroenteritis in children. Aliment
Pharmacol Ther 2011;34:862-7.
Varavithya W, Posayanond P, Tontisirin K, et al. Oral hydration in infantile diarrhoea. Southeast Asian J Trop Med Public Health 1978;9:414-9.
Varsano I, Eidlitz-Marcus T, Nussinovitch M, et al. Comparative efficacy of ceftriaxone and ampicillin for treatment of severe shigellosis in children. J Pediatr
1991;118:627-32.
Verrotti A, Tocco AM, Coppola GG, et al. Afebrile benign convulsions with mild gastroenteritis: a new entity? Acta Neurol Scand 2009;120:73-9.
Vinh H, Anh VT, Anh ND, et al. A multi-center randomized trial to assess the efficacy of gatifloxacin versus ciprofloxacin for the treatment of shigellosis in
Vietnamese children. PLoS Negl Trop Dis 2011;5:e1264.
Vrints M, Mairiaux E, Van Meervenne E, et al. Surveillance of antibiotic susceptibility patterns among Shigella sonnei strains isolated in Belgium during the
18-year period 1990 to 2007. J Clin Microbiol 2009;47:1379-85.
Vukelic D, Trkulja V and Salkovic-Petrisic M. Single oral dose of azithromycin versus 5 days of oral erythromycin or no antibiotic in treatment of
campylobacter enterocolitis in children: a prospective randomized assessor-blind study. J Pediatr Gastroenterol Nutr 2010;50:404-10.
Wadhwa N, Natchu UC, Sommerfelt H, et al. ORS containing zinc does not reduce duration or stool volume of acute diarrhea in hospitalized children. J
Pediatr Gastroenterol Nutr 2011;53:161-7.
Waisbourd-Zinman O, Ben-Ziony S, Solter E, et al. Hospitalizations for nosocomial rotavirus gastroenteritis in a tertiary pediatric center: a 4-year prospective
study. Am J Infect Control 2009;37:465-9.
Waisbourd-Zinman O, Ben-Ziony S, Solter E, et al. The percentage of nosocomial-related out of total hospitalizations for rotavirus gastroenteritis and its
association with hand hygiene compliance. Am J Infect Control 2011;39:166-8.
Wiegering V, Kaiser J, Tappe D, et al. Gastroenteritis in childhood: a retrospective study of 650 hospitalized pediatric patients. Int J Infect Dis 2011;15:e401-7.
Wildi-Runge S, Allemann S, Schaad UB, et al. A 4-year study on clinical characteristics of children hospitalized with rotavirus gastroenteritis. Eur J Pediatr
2009;168:1343-8.
Williams DJ, Edwards KM, Payne DC, et al. Decline in gastroenteritis-related triage calls after rotavirus vaccine licensure. Pediatrics 2012;130:e872-8.
Williams MD, Schorling JB, Barrett LJ, et al. Early treatment of Campylobacter jejuni enteritis. Antimicrob Agents Chemother 1989;33:248-50.
Wong CS, Mooney JC, Brandt JR, et al. Risk factors for the hemolytic uremic syndrome in children infected with Escherichia coli O157:H7: a multivariable
analysis. Clin Infect Dis 2012;55:33-41.
Yung M and Keeley S. Randomised controlled trial of intravenous maintenance fluids. J Paediatr Child Health 2009;45:9-14.

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ESPGHAN/ESPID Guidelines for the Management of AGE in Children in Europe

RISK FACTORS FOR SEVERE AND/OR PERSISTENT DISEASE

Pathogens Rates Virus:

community- Patients with Rates (%) 24.4%, 30.2% costs

Intravenous Rates 172 (77.13%) 21

had RV, 188 Salmonella Diarrhea mean 3.8±0.1 vs more

Campylobact Weighted PD 6% vs no associated with

week until Isolation of Rates 7.9% (3/38)

diarrhea (46 s Antibody Median 68 [28; 110] vs with persistent

Table 1.2.1. Risk factor: younger age

>10 days were Isolation of Rates RV 59 (57.8%) NV

Detection of EAEC Rates CVD432+ : Acute inchildren >12 months

*diarrhea lasting > 14 days was considered persistent

home at least Passive surveillance Incidence 1.26 (children < 6

Table 1.2.2. Risk factor: Feeding practice

infant stool and Consumption of Poisson p= 0.012 and mortality, caused

Antibody (IgA) Median 83 [19; 243] vs have implications for

Table 1.2.3. Chronic diseases and Immune deficits

Malnutrition 2.39 (2.14-

Day TG, Case-series _ _ _ _ First reported cluster

outpatients). Lethargy (RV frequency 53% vs 27%, to children with non

AGE=Acute gastroenteritis; NV= Norovirus; OR=odds ratio; QoS=Quality of Study; RV=Rotavirus.

Table 1.4.1. Hospitalization

RV-infected Rates (%) 76–78% The main

Nosocomial Rates (%) 2 and 13%

Table 1.4.2. Socioeconomic factors

Table 1.4.3. Day care attendance

CLINICAL EVALUATION AND DISEASE SEVERITY

Table 2.1. What are the indications for a medical visit?

Table 2.2.1. Bacterial versus viral

Children without frequency 4% vs 19%, p=0.01

Metabolic Number 85 (4%) vs 56 (2%), p<0.001

Table 2.2.2. Systemic Involvement

2.3 How is dehydration assessed?

Table 2.3.1. Clinical dehydration scale

Table 2.3.2. Severity scores

Table 2.3.3. Clinical and laboratory assessment

Table 2.3.4. Standardized Scoring System

Table 2.3.5. Ultrasound

Table 2.3.6. Hand-held bladder ultrasound

Table 2.3.7. Digital videography to measure capillary refill time

Table 2.3.8. Bioelectric impedance

Table 2.3.9. Plasma water

Table 3.1. Is There Any Reliable Hematological Marker of Bacterial Diarrhea?

Table 3.2. Stool markers for identification of bacterial diarrhea

AUC fCP vs CRP,

Table 4.1. What are the indications for hospitalization?

Table 4.3. What are the indications for nasogastric rehydration?

Estimated pain with Median±SD 64±18 vs

Duration of diarrhea 8 (960) Weighted -5.9 (-12.7 to

4.4. What are the indications for intravenous rehydration?

interventions, all Persistence of rate 80% vs days after

problems. Hypernatemia statistically

Table 4.4.2. Regimen

to AGE. saline in 3 h Return visits Frequency 15.6%(6.5 to

Table 4.4.3. Treatment of hypernatremia

Table 4.5. When to discharge a child admitted because of gastroenteritis

Table 5.1. Rehydration

Table 5.2. Nutritional management

Table 5.3. Pharmacological Therapy

5.4. Anti-infective therapy

Reference Study type Population Intervention Comparison Outcome