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Published by Oxford University Press on behalf of the International Epidemiological Association. International Journal of Epidemiology 2010;39:i75–i87
ß The Author 2010; all rights reserved. doi:10.1093/ije/dyq025

The effect of oral rehydration solution and

recommended home fluids on diarrhoea
mortality
Melinda K. Munos, Christa L Fischer Walker and Robert E Black

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Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

Corresponding author. Department of International Health, Johns Hopkins Bloomberg School of Public Health,
615 North Wolfe St. Rm E5535, Baltimore, MD 21205, USA. E-mail: [email protected]

Background Most diarrhoeal deaths can be prevented through the prevention

and treatment of dehydration. Oral rehydration solution (ORS)
and recommended home fluids (RHFs) have been recommended
since 1970s and 1980s to prevent and treat diarrhoeal dehydration.
We sought to estimate the effects of these interventions on diar-
rhoea mortality in children aged <5 years.
Methods We conducted a systematic review to identify studies evaluating the
efficacy and effectiveness of ORS and RHFs and abstracted study
characteristics and outcome measures into standardized tables. We
categorized the evidence by intervention and outcome, conducted
meta-analyses for all outcomes with two or more data points and
graded the quality of the evidence supporting each outcome. The
CHERG Rules for Evidence Review were used to estimate the effec-
tiveness of ORS and RHFs against diarrhoea mortality.
Results We identified 205 papers for abstraction, of which 157 were
included in the meta-analyses of ORS outcomes and 12 were
included in the meta-analyses of RHF outcomes. We estimated
that ORS may prevent 93% of diarrhoea deaths.
Conclusions ORS is effective against diarrhoea mortality in home, community
and facility settings; however, there is insufficient evidence to esti-
mate the effectiveness of RHFs against diarrhoea mortality.
Keywords Oral rehydration solution, oral rehydration therapy, recommended
home fluids, diarrhoea, child, systematic review, meta-analysis

In 1960s and 1970s, physicians working in South

Background Asia developed a simple oral rehydration solution
Diarrhoeal diseases are a leading cause of mortality (ORS) containing glucose and electrolytes that could
in children aged <5 years, accounting for 1.7 million be used to prevent and treat dehydration due to diar-
deaths annually.1 Because the immediate cause of rhoea of any aetiology and in patients of all ages.2–8
death in most cases is dehydration, these deaths are At the time ORS was developed, placebo-controlled
almost entirely preventable if dehydration is pre- trials would have been unethical given the efficacy of
vented or treated. Until 1970s, intravenous (IV) infu- IV therapy, and to our knowledge none exists. The
sion of fluids and electrolytes was the treatment of randomized controlled trials (RCTs) of ORS conducted
choice for diarrhoeal dehydration, but was expensive to confirm its efficacy instead used a comparator such
and impractical to use in low-resource settings. as IV therapy or alternative formulations of ORS.

i75
i76 INTERNATIONAL JOURNAL OF EPIDEMIOLOGY

Similarly, studies conducted in community settings Methods

to assess the effectiveness of ORS did not actively
withhold ORS from the comparison area but instead Per CHERG Guidelines, we systematically reviewed
evaluated the effectiveness of promotional campaigns published literature from PubMed, the Cochrane
or alternative delivery systems compared with routine Libraries, and the WHO Regional Databases to identify
health system delivery. studies examining the effect of oral rehydration strate-
In 1970s, the World Health Organization (WHO) gies on diarrhoea morbidity and mortality in children
recommended that an ORS formulation with total aged <5 years. Search terms included combinations
osmolarity 311 mmol/l be used for prevention and of diarrhea, dysentery, rotavirus, fluid therapy, oral rehydra-
treatment of diarrhoeal dehydration. However, alter- tion solution, oral rehydration therapy, recommended home
native formulations continued to be investigated in fluid and sugar salt solution. We limited the search to
an attempt to develop an ORS formulation that studies that included children aged <5 years and
would decrease stool output or have other clinical studies in English, French, Spanish, Portuguese and

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benefits. These efforts led, in 2004, WHO to recom- Italian.
mend low osmolarity ORS (with total osmolarity of
245 mmol/l and reduced levels of glucose and Inclusion/exclusion criteria and definitions
sodium), which was associated with reduced need For the purposes of this review, we defined and
for unscheduled IV therapy, decreased stool output reviewed three categories of oral rehydration strategies:
and less vomiting when compared with the original ORS, RHFs and ORT. We defined ORS as an electrolyte
formulation.9,10 solution containing sodium, chloride, potassium, bicar-
As countries launched diarrhoeal disease control bonate or citrate and glucose or another form of sugar or
programmes to roll out ORS, they faced difficulties starch. Formulations containing small amounts of other
in ensuring access and achieving high coverage minerals, such as magnesium, were included in this
levels, in part due to inadequate manufacturing category, but solutions containing amino acids such as
capacity. In an effort to improve provision of fluids glycine or alanine were excluded. We also excluded
in early diarrhoea episodes to prevent the develop- solutions containing zinc, because it was not possible
ment of dehydration, diarrhoeal disease control to separate the effects of ORS and zinc on diarrhoea
programmes promoted the use of additional fluids morbidity. Both reduced osmolarity ORS (total osmo-
and home-made solutions such as rice water and larity 4250 mmol/l, per Hahn10) and higher osmolarity
sugar salt solution [collectively referred to as recom- ORS (up to 370 mmol/l) were included in our review.
mended home fluids (RHFs)].11,12 RHFs were eventu- For RHFs, we included all possible home fluid alter-
ally incorporated into the WHO recommendations for natives in our review, including sugar–salt solution,
prevention of dehydration. Unfortunately, over the cereal–salt solution, rice–water solution and additional
years, programmes have combined ORS and RHFs fluids such as plain water, juice, tea or rice water. If the
into a general and poorly defined oral rehydration study intervention was promotion or provision of both
therapy (ORT) category in which the respective roles ORS and RHF in the same area and the effects and cov-
of ORS and RHFs are not well delineated. erage estimates of the two interventions could not be
Recent Cochrane reviews have estimated the efficacy separated, we categorized it as ORT. Such studies were
of ORS compared with IV therapy, and reduced osmo- generally large-scale programme evaluations.
We included quasi-experimental, pre/post, observa-
larity ORS compared with original ORS, against treat-
tional and randomized and cluster-randomized trials
ment failure.10,13 Additionally, in 1998, a Cochrane
reporting any of the following outcomes for children
review examined the effect of rice-based, compared aged <5 years: all-cause or diarrhoea-specific mortal-
with glucose-based, ORS on stool output and duration ity, diarrhoea hospitalizations, referrals to hospitals or
of diarrhea.14 However, these reviews focused on health centres for diarrhoea treatment, or treatment
RCTs of ORS conducted in hospitals or clinical settings failure. Studies in developed countries were excluded
and did not examine mortality as an outcome or the unless conducted in a low-resource setting, such as
broader category of RHFs as an intervention. To our native American reservations. Treatment failure was
knowledge, there are no systematic reviews or corre- generally defined as the need for unscheduled IV
sponding meta-analyses assessing the effect of ORS or therapy, but we accepted other definitions provided
RHFs on diarrhoea-specific mortality. We present that they reflected failure of the therapy to produce
evidence from systematic reviews and meta-analyses or maintain clinical improvement in the subjects’
drawing upon data from community- and dehydration state. Studies that defined treatment fail-
facility-based studies to estimate the effectiveness of ure in terms of stool volume or duration of diarrhoea
ORS, and, separately, RHFs on diarrhoea morbidity were excluded.
and mortality in children aged <5 years. We then cor-
relate the effectiveness estimates with achieved cover- Abstraction
age levels to generate an estimate of the effect of each We abstracted all studies meeting our acceptance cri-
intervention on cause-specific mortality. teria into standardized tables, categorized by outcome,
 EFFECT OF ORAL REHYDRATION SOLUTION AND HOME FLUIDS ON DIARRHOEA MORTALITY i77

study design and type of oral rehydration strategy. Hospitalization/referral

Abstracted variables included study identifiers and The clinical guidelines and processes for hospitaliza-
context, design and limitations, population, character- tion and referral in the studies we identified were
istics of the intervention and control and outcome variables and often not well described. Moreover,
measures. Based on these data, we graded each this outcome can be confounded by differences in
study according to the CHERG adaptation of the care-seeking or referral practices between study
GRADE technique.15 Scores were decreased by half a arms, particularly in quasi-experimental studies, and
grade for each design limitation; observational stu- the studies included in our review did not adequately
dies, including pre/post studies, received a very low address or adjust for this possibility. Given these con-
grade. siderations, a meta-analysis was not appropriate for
this outcome, and none was conducted.
Analysis

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We summarized the evidence for ORS and RHFs by Overall effectiveness estimate
outcome in a separate table and graded the quality of Applying the CHERG Rules for Evidence Review,15 for
evidence for each outcome, decreasing the score for each outcome, we considered the quality of the evi-
observational study designs, heterogeneity of study dence, number of events and generalizability of the
outcomes or lack of generalizability of the study pop- study population and outcome to diarrhoea-specific
ulations or interventions. We did not produce a sum- mortality to estimate the effects of ORS and RHFs
mary table for ORT because our goal was to generate on diarrhoea mortality in children aged <5 years.
estimates of the individual rather than joint effective-
ness of ORS and RHFs, as each has different roles in
diarrhoea management. For each outcome with more
than one study, we conducted both fixed and random
Results
effects meta-analyses. Our searches identified 2397 titles; after screening
titles and abstracts, we reviewed 404 papers for our
Mortality inclusion/exclusion criteria and outcomes of interest
For diarrhoea-specific mortality, we included rando- (Figure 1). We abstracted 205 papers into our final
mized, cluster-randomized and quasi-experimental database: 184 reporting data on ORS, 23 on RHFs
studies in the meta-analysis. Observational studies and 18 on ORT as defined above. For the outcomes
(other than quasi-experimental studies) that did not of diarrhoea and all-cause mortality, we excluded
control for confounding were excluded, as were case– many papers in our final database from the meta-
control studies and those that did not provide an ade- analysis because they used observational study
quate estimate of coverage in the intervention arm. designs and did not control for confounding, did not
We defined coverage as the proportion of diarrhoea report an adequate coverage indicator, had no relevant
episodes in children aged <5 years for which the comparison group or used a case–control design. These
child received ORS or RHFs. We excluded studies in studies are shown in Supplementary tables 1 and 2,
which a comparator or alternative delivery system was but were not included in the meta-analyses or
used in the comparison arm, because the resulting summary tables (Supplementary tables 1 and 2).
relative risk did not provide meaningful information
on the effect of ORS or RHFs on diarrhoea morbidity ORS
or mortality. For ORS and, separately, RHFs, we We identified 21 papers reporting diarrhoea-specific
reported the pooled relative reduction in diarrhoea- mortality, 3 reporting all-cause mortality, 20 reporting
specific mortality and 95% confidence interval (CI). hospitalization/referral and 155 reporting treatment
In the case of heterogeneity, we reported the failure that met our inclusion/exclusion criteria
DerSimonian–Laird pooled relative reduction and (Supplementary table 1). Of these, three papers
95% CI. reporting diarrhoea mortality and 153 reporting treat-
ment failure were included in the meta-analyses.
Treatment failure Table 1 presents the summary characteristics of
Observational studies and RCTs of ORS or RHFs these studies and meta-analysis results by outcome.
assessing treatment failure, including those that For the outcomes of diarrhoea mortality and treat-
used a comparator, were included in the meta- ment failure, there was evidence to support the effec-
analysis. For included studies, instead of a relative tiveness of ORS. A fixed effect meta-analysis showed
risk, we analysed the absolute treatment failure rate a 69% (95% CI: 51–80%) pooled relative reduction in
for each therapy that met our inclusion criteria. We diarrhoea mortality in communities in which ORS
conducted separate and combined meta-analyses for was promoted compared with comparison areas,
RCTs and observational studies and reported the with no indication of heterogeneity (Table 1). A
Mantel–Haenszel pooled failure rate and 95% CI, or random effects meta-analysis similarly showed a
the DerSimonian–Laird pooled failure rate and 95% CI very low-pooled treatment failure rate (0.2%; 95%
if there was evidence of heterogeneity for each. CI: 0.1–0.2%) for ORS. Studies reporting treatment
i78 INTERNATIONAL JOURNAL OF EPIDEMIOLOGY

109 studies identified in 3 Cochrane reviews

166 studies obtained from

subject area experts

PubMed, Cochrane Library and

WHO Global Health Library
searches identifying 2122 studies

2397 titles and abstracts screened for eligibility

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Titles and abstracts screened

404 papers reviewed for eligibility

199 papers excluded because

No relevant outcomes/insufficient data on outcomes (n=57);
Data not reported by age/treatment group (n=36);
Did not include the population of interest (n=30);
Review, comment, or treatment guideline (n=27);
Methods not sufficiently described (n=22);
Reported same data as other included papers (n=6); or
Did not use ORS/RHFs or co-interventions made it
impossible to isolate effect of ORS/RHFs (n=5)

205 papers identified for abstraction

Papers abstracted

184 papers with data 23 papers with 18 papers with

on ORS data on RHF data on ORT

Figure 1 Search process for ORS and RHFs

failure were almost universally conducted in hospital 47–57% relative decrease in hospitalization and
or clinic settings. 29–89% relative decreases in referrals to health
For the outcome of hospitalization/referral, 6 of 20 centres in the intervention areas.
studies included a relevant comparison arm: five We applied the CHERG Rules for Evidence Review15
quasi-experimental studies and one pre/post study. to the evidence presented in Table 1. We used the
Of the five quasi-experimental studies, two did not pooled effect size for diarrhoea mortality, as it
clearly report the coverage achieved, one provided was more conservative than the effect size for
regular home visits by nurses and a health education severe morbidity (treatment failure). The mean and
component in the intervention but not comparison median coverage levels in the intervention arms
arms and none discussed care-seeking practices in of the diarrhoea mortality studies were 74%; assum-
intervention and control areas. The outcomes of ing a linear relationship between coverage and mor-
these studies were mixed, with two studies reporting tality reduction, at 100% coverage a 93% relative
increases in hospitalization in the intervention relative reduction in diarrhoea mortality would be expected
to the control area, whereas the other studies reported (Figure 2).
Table 1 Quality assessment of trials of ORS

Quality assessmenta Summary of findings

Directness No. of events Effect
Generalizability Relative
No. of Generalizability to to intervention reduction
studies Design Limitations Consistency population of interest of interest Intervention Control (95% CI) Comments
Diarrhoea mortality rate: low outcome-specific quality
Three18–20 Quasi No adjustment for Consistent benefit India, Bangladesh and No studies used 27/11696 41/5295 69% (51–80%) Fixed effect
experimental confounding variables from all studies Burma ( 0.5) reduced osmolarity child-years child meta-analysis
( 1) ( 0.5); ORS used in ORS years
control arms in most
cases, but at a lower
rate than in interven-
tion arms

Treatment failure: moderate outcome-specific quality


153 total RCTs and No true control arm; Heterogeneity from South/Southeast Asia, About 26 used low 1283/18 084 NA 0.2% (0.1–0.2%) Pooled failure rate
observational most studies are hospi- meta-analysis Eastern Mediterranean, osmolarity ORS About episodes Random effects
tal based; many obser- ( 0.5) Latin America, North/ 26 used rice- or meta-analysis
vational ( 0.5) South/East/West Africa, cereal-based ORS
Eastern Europe and
Apache reservations in
USA
124 
10421 RCTs No true control arm; Heterogeneity from South/Southeast Asia, About 22 used low 734/9449 NA 0.2% (0.1–0.2%) Pooled failure rate
most studies hospital meta-analysis Eastern Mediterranean, osmolarity ORS (total episodes Random effects
based ( 0.5) Latin America and osmolarity meta-analysis
North/West/East Africa 4 250 mmol/L);
approximately 26 used
rice- or cereal-based
ORS

49125–172 Observational No adjustment for Heterogeneity from Latin America, South/ About four studies used 549/8635 NA 0.3% (0.2–0.4%) Pooled failure rate
(DEC Ashley confounding meta-analysis Southeast Asia, Eastern low-osmolarity ORS episodes Random effects
et al., ( 0.5) Mediterranean, North/ meta-analysis
Unpublished, South/East/ West
1980.) Africa, Eastern Europe
and Apache reserva-
tions in USA
a
See Walker et al.15 for a description of the quality assessment and grading methods.
EFFECT OF ORAL REHYDRATION SOLUTION AND HOME FLUIDS ON DIARRHOEA MORTALITY
i79

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i80 INTERNATIONAL JOURNAL OF EPIDEMIOLOGY

meta-analysis
Random effects
Pooled failure
Possible Outcome Application of
Standard Rulesa

Comments
Measures
Rules 1 & 2: Do not apply

rate
Diarrhea Mortality (n=3; 68 events) Very low quality evidence for cause-
ORS reduces mortality by 69% (95% CI: 51-80%) specific mortality
given mean coverage of 74% (range 52-96%)
Rule 3: APPLY


(93% reduction with 100% coverage)

0 ( 0.1, 0.1%)
Treatment Failure (n=153; 1283 events)
ORS fails to improve or maintain hydration in 0.2% of
treated episodes (0.1-0.2%)
reduction
Intervention Control (95% CI)
Summary of findings

Relative
Effect

Very low quality evidence for diarrhea mortality reduction and

moderate quality evidence for improvement in serious morbidity:
Plausible

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Figure 2 Application of standardized rules for choice of
NA

final outcome to estimate effect of ORS on the reduction

of diarrhoea mortality. aSee Walker et al.15 for a description
No of events

episodes

of the CHERG Rules for Evidence Review

31/784

RHFs
sugar–salt solution;

solution; two did

We identified and abstracted five studies reporting

not define RHF
one used sugar
Nine used cereal/

diarrhoea mortality, one reporting all-cause mortality,

Generalizability
to intervention

five reporting hospitalization or referral and 14 report-

ing treatment failure for RHFs (Supplementary
of interest

( 0.5)

table 2). For the outcomes of diarrhoea and all-cause

mortality, no studies met the required study quality
criteria for inclusion in the meta-analyses.
We included 12 studies in the meta-analysis of
North/West/East Africa

treatment failure and found a pooled failure rate of

See Walker et al.15 for a description of the quality assessment and grading methods.
Studies clinic- or Heterogeneity South/Southeast Asia,

and Latin America.

RHFs not tested in

0% (95% CI: 0.1 to 0.1%) (Table 2). However, each

of these studies included dehydrated patients and was
the home ( 1)

conducted in a hospital or clinic setting. Studies

Generalizability
Quality assessment and summary outcomes of trials of RHFs

Quality assessmenta

to population

assessed sugar solution and sugar- or cereal–salt solu-

of interest
Directness

tions; none assessed other RHFs such as plain water

or rice water. Due to the low quality of evidence
(i.e. no community-based studies) for serious morbid-
ity and the lack of well-designed studies assessing the
effect of RHFs on mortality, we did not estimate an
Treatment failure: low/very low outcome-specific quality

from meta-
Consistency

effect of RHFs on diarrhoea mortality (Figure 3).

analysis
( 0.5)

ORT
We found 14 studies reporting diarrhoea mortality,
( 0.5); no true

one reporting all-cause mortality and five reporting

hospital based

dehydration or treatment failure for ORT that met

control arm

our inclusion/exclusion criteria (Supplementary

Design Limitations

table 3). The studies abstracted are suggestive of an

effect of joint promotion of ORS and/or RHF on diar-
rhoea mortality. Of the studies reporting mortality
data with comparison groups (including historical
comparison groups), all reported a decline in diar-
RCTs

rhoea or all-cause mortality, although the magnitude

of the declines, time periods over which they occurred
118,123,173

and the associated coverage levels varied greatly.

1227,29,39,
40,53,67,
73,87,98,

These studies primarily used pre/post designs and in

Table 2

most cases did not adjust for confounding; thus, it is

studies
No of

not possible to determine whether the declines were

causally associated with the use of ORS and RHFs, or
a
 EFFECT OF ORAL REHYDRATION SOLUTION AND HOME FLUIDS ON DIARRHOEA MORTALITY i81

Possible Outcome Application of intended to be used for home-based fluid manage-

Measures Standard Rulesa ment to prevent dehydration, with possible indirect
effects on mortality. However, the only well-
Rules 1 & 2: Do not apply
No evidence for cause-specific mortality controlled studies of RHFs were conducted in hospital
settings and included only sugar–salt solution and
cereal–salt solution. Whereas we included these stu-
Treatment Failure (n=12; 31 events) Rules 3 & 5: Do not apply
RHFs fail to improve or maintain hydration in Very low quality evidence for serious dies in our meta-analysis of RHF treatment failure,
hospital/clinic settings in 0% of treated episodes morbidity
(−0.1 - 0.1%) the results cannot be generalized to the administra-
tion of RHFs by a caregiver in the home and cannot
Rules 4, 6 & 7: Do not apply be assumed to be representative of all current RHFs.
No evidence for mild or moderate
morbidity
Community-based studies of RHFs, which are not
only inherently less controlled but also more relevant
than hospital-based studies, have been conducted and

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No evidence for mortality and referral and poor generalizability of the intervention for
treatment failure: Insufficient data to estimate an effect of RHFs on mortality
were abstracted into Supplementary table 2, but
either did not include a relevant comparison arm or
Figure 3 Application of standardized rules for choice of failed to adequately document the coverage achieved,
final outcome to estimate effect of RHFs on the reduction making it difficult to interpret their results. Moreover,
of diarrhoea mortality (aSee Walker et al.15 for a description we were unable to find studies meeting our inclusion
of the CHERG Rules for Evidence Review.) criteria that assessed other RHFs such as water and
rice water. Thus, our findings may not be representa-
tive of the full range of RHFs.
ORS is a simple, proven intervention that can be
with other interventions and changes occurring in the used at the community and facility level to prevent
community during the same time period. and treat diarrhoeal dehydration and decrease diar-
rhoea mortality. Whereas ORS is highly effective, cov-
erage levels remain low in most countries. It is
Discussion essential that ORS coverage be increased to achieve
reductions in diarrhoea mortality; to do so, operations
We found a large body of evidence evaluating the effi- and implementation research is needed to better
cacy and effectiveness of ORS, and a more limited understand how to deliver ORS effectively and pro-
number of studies assessing RHFs. Based on this evi- mote its use at home and facility level as part of
dence, we estimated that ORS may reduce diarrhoea appropriate case management of diarrhoea.
mortality by up to 93%, but were unable to estimate In contrast to ORS, RHFs were designed and recom-
the effectiveness of RHFs against diarrhoea mortality mended as a home-based intervention to prevent
because no studies were conducted outside hospital set- diarrhoeal dehydration, but this message has
ting, which is inconsistent with the definition of ‘home become confused as diarrhoea control programmes
fluids’ (Figures 2 and 3). Whereas the overall quality of have evolved. Moreover, for RHFs to be used appro-
evidence supporting the effectiveness of ORS against priately at home, caregivers must be able to assess
diarrhoea mortality was low as a result of non- whether a child is dehydrated and correctly determine
randomized study designs, our conclusions are whether to provide RHFs or ORS. Thus, whereas there
strengthened by the consistency of the effect size and is evidence suggesting that RHFs may be effective in
direction among the studies included and those preventing dehydration, its correct implementation
excluded from the meta-analysis. Moreover, the biolog- and the associated behaviour change communication
ical basis for ORS, co-transport of glucose and sodium messages are complex. From a programmatic perspec-
across the epithelial layer in the small intestine is well tive, promoting the use of ORS for all diarrhoea
established and supports a protective effect of ORS episodes might, therefore, be both simpler and more
against fluid losses and electrolyte imbalances.16,17 effective than promoting ORS and RHFs as a pack-
We correlated ORS effectiveness with coverage, age and teaching caregivers when and how to use
using the absolute coverage levels reported for the each.
intervention arms. However, in most community-
based studies, ORS was also available and used at a
low level in the comparison arms. The effective cov-
erage level (difference in coverage between the inter- Supplementary data
vention and comparison arms) was thus lower than Supplementary data are available at IJE online.
the absolute coverage level used in our calculations.
For this reason, our approach is conservative and
likely overestimates the coverage needed to achieve
a particular mortality reduction. Funding
RHFs were not designed as an intervention to US Fund for UNICEF from the Bill & Melinda Gates
directly decrease diarrhoea mortality, but were instead Foundation (grant 43386 to ‘Promote evidence-based
i82 INTERNATIONAL JOURNAL OF EPIDEMIOLOGY

14
decision making in designing maternal, neonatal and Fontaine O, Gore SM, Pierce NF. Rice-based oral rehydra-
child health interventions in low- and middle-income tion solution for treating diarrhoea. Cochrane Database Syst
countries’). MKM is supported by a training grant Rev 2000;(2):CD001264.
15
from the U.S. National Institutes of Health (grant Walker N, Fischer Walker CL, Bahl R et al. The CHERG
T32HD046405 for ‘International Maternal and Child methods and procedures for estimating effectiveness of
Health’). interventions on cause-specific mortality. Int J Epidemiol
2010;39(Suppl 1):i21–31.
16
Schedl HP, Clifton JA. Solute and water absorption by the
human small intestine. Nature 1963;199:1264–67.
17
Schultz SG, Zalusky R. Ion transport in isolated rabbit
Acknowledgement ileum. Ii. The interaction between active sodium and
We thank our colleagues at WHO and UNICEF for active sugar transport. J Gen Physiol 1964;47:1043–59.
their review of the manuscript and valuable feedback. 18
Kumar V, Kumar R, Datta N. Oral rehydration therapy

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Conflict of interest: none declared. J Diarrhoeal Dis Res 1987;5:159–64.
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