Progress and barriers for the control of diarrhoeal disease

Review

Progress and barriers for the control of diarrhoeal disease

Mathuram Santosham, Aruna Chandran, Sean Fitzwater, Christa Fischer-Walker, Abdullah H Baqui, Robert Black

Discovery of intestinal sodium-glucose transport was the basis for development of oral rehydration solution, and was Lancet 2010; 376: 63–67
hailed as potentially the most important medical advance of the 20th century. Before widespread use of oral rehydration
solution, treatment for diarrhoea was restricted to intravenous fluid replacement, for which patients had to go to a Department of International
health-care facility to access appropriate equipment. These facilities were usually neither available nor reasonable to Health, Johns Hopkins
use in the resource-poor settings most affected by diarrhoea. Use of oral rehydration solution has stagnated, despite Bloomberg School of Public
being effective, inexpensive, and widely available. Thus, diarrhoea continues to be a leading cause of child death with Health, Baltimore, MD, USA
consistent mortality rates during the past 5 years. New methods for prevention, management, and treatment of (Prof M Santosham MD,
diarrhoea—including an improved oral rehydration formulation, zinc supplementation, and rotavirus vaccines— A Chandran MD, S Fitzwater MHS,
make now the time to revitalise efforts to reduce diarrhoea mortality worldwide. C Fischer-Walker PhD,
Prof A H Baqui DrPH,
Introduction diarrhoea-control programmes every year.9 By 1988, more Prof R Black MD)
than 100 countries had established national programmes
Diarrhoea causes 1·3 million deaths in children younger for control of diarrhoeal disease on the basis of WHO Correspondence to:
than 5 years every year.1 Some countries in south Asia recommendations.10 Prof Mathuram Santosham,
and Africa have especially high diarrhoea mortality rates Department of International
(figure 1).1 Reduction of this mortality burden is crucial to Activities in diarrhoea-control programmes varied Health, Johns Hopkins
achieve the UN’s Millennium Development Goal 4 to widely,9 and included changes to medical-school curricula, Bloomberg School of Public
decrease the child mortality rate by two-thirds between training of partly skilled health workers, participation of Health, 615 North Wolfe Street,
1990 and 2015. religious leaders, educational campaigns in schools, and Baltimore, MD 21205, USA
modifications to use of oral rehydration formulations to [email protected]
The cause of infectious diarrhoea varies worldwide. In fit local traditions and beliefs. Mass media campaigns
low-income and middle-income countries, where were set up around the world, and many political leaders
pathogen transmission occurs mainly through and celebrities endorsed the use of oral rehydration
contaminated food or drinking water, bacterial and viral solution. Outpatient oral rehydration centres—where
pathogens are responsible for most disease.2 Children mothers were taught to treat their children with the
younger than 5 years in developing countries have a solution and continue feeding—replaced hospital wards
median of three episodes of diarrhoea every year.3 Fluid where children with diarrhoea from all causes had been
loss and dehydration is the cause of death in nearly all treated with intravenous fluids. Production of powder for
patients with diarrhoea. reconstitution increased from 51 million packets in 1979
to 800 million in 1992—most of which were produced in
Over 3 decades ago, the discovery of intestinal sodium- developing countries.11 Because of the benefits of oral
glucose transport, which was the basis for the formulation, its use spread to developed countries; a rare
development of oral rehydration solution, was hailed as example of a health intervention pioneered in developing
the most important medical advance of the 20th century.4 countries being transferred to developed ones.12
Although use of rehydration solution does not lessen
diarrhoea incidence, more than 90% of dehydration from Diarrhoea-control programmes have proved highly
diarrhoea can be remedied with its use—leading WHO effective.13 Investigators for Egypt’s national control of
to make it the mainstay of diarrhoea treatment.5 Antibiotic diarrhoeal diseases project showed a substantial increase
therapy in addition to oral rehydration solution is in awareness and use of oral rehydration in the country
indicated only for cases of bloody diarrhoea or cholera.5,6 between 1981 and 1990, and a fall in the infant diarrhoeal
Evidence that zinc therapy reduces the duration and death rate from 35·7 to 9·3 per 1000 livebirths—a
severity of diarrhoeal episodes and recurrence of such 74% reduction with no concomitant decrease in diarrhoea
illness led WHO and UNICEF to recommend that zinc incidence. Non-diarrhoeal mortality also fell in this
be provided with oral rehydration solution for all episodes decade, but only by 28%.14 Similarly, results from a large
of childhood diarrhoea.7 diarrhoea-control programme15 in Brazil showed a 67%
reduction in the proportion of registered deaths due to
Oral rehydration solution was initially assessed for diarrhoea in infants from 1980 to 1989, whereas non-
cholera treatment, and then shown to be effective diarrhoeal mortality dropped by only 32%.
irrespective of cause of diarrhoea or age of the patient.
The WHO programme for the control of diarrhoeal By 1988, an estimated 60% of children in developing
disease began in 1978, and placed the main emphasis on countries younger than 5 years lived in areas with access
management of clinical diarrhoeal illness with this to oral rehydration solution, compared with 5% in 1982.5
solution (table) or home mixtures of sugar and salt, with The percentage of cases of diarrhoea treated with this
continued feeding to prevent a diarrhoea–malnutrition solution or appropriate home fluids increased from 12%
cycle.9 International funding for diarrhoea control in 1984 to 37% in 1992.11 Results from 15 hospitals in
expanded greatly during the subsequent decade, with 11 countries showed that hospital admissions for
tens of millions of dollars going to research and

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Death rate per
100 000 children

≥500
100–<500
50–<100
10–<50
<10
No data

Figure 1: Deaths due to diarrhoea per 100 000 children younger than 5 years
Data from reference 1..

Glucose Original oral Low osmolarity there was a reduction in stool output, vomiting, and
Sodium rehydration oral rehydration unscheduled intravenous treatment in patients who
Chloride solution8 solution7 received low osmolarity solution compared with those
Potassium given original solution. On the basis of an expert panel’s
Citrate 111 75 recommendations, WHO changed its guidance in 2002,
Total osmolarity (mOsm/L) 90 75 for treatment of children and adults with diarrhoea, to
80 65 use of low osmolarity solution (table).7,8
20 20
30 10 Zinc recommendations for diarrhoea
331 245
Zinc decreases the duration and severity of diarrhoeal
Data are mmol/L unless otherwise stated. episodes when given with oral rehydration solution
(panel). Another meta-analysis18 showed that treatment
Table: Composition of original and low-osmolarity WHO oral with zinc noticeably decreased the duration of acute and
rehydration solution persistent diarrhoea. Furthermore, a 10–14 day course of
zinc during and after diarrhoea decreases the recurrence
diarrhoea were reduced by a median of 61% after the of diarrhoea in the next 2–3 months.19
introduction of oral rehydration programmes.16
Worldwide distribution of oral solution helped to reduce Introduction of zinc to community programmes
the estimated number of child deaths due to diarrhoea resulted in increased use of oral rehydration solution,
from more than 4·6 million in 1980 to 3·3 million in decreased use of unnecessary antibiotics, and a reduced
1990, to 1·8 million in 2004, and to 1·3 million in 2008.1–3 need for medical visits for acute diarrhoea.21 Two large-
scale effectiveness studies20,21 compared communities
Updated oral rehydration solution given zinc and oral rehydration for acute diarrhoea
recommendations episodes with those given oral rehydration solution alone;
addition of zinc led to a fall in hospital admissions for
Concerns that the sodium concentration in original WHO diarrhoea. In India, Bhandari and colleagues21 reported a
oral rehydration solution could lead to hypernatraemia— reduction in all-cause diarrhoea (odds ratio [OR] 0·56,
especially in patients with non-cholera diarrhoea in which 95% CI 0·41–0·75), and diarrhoea-related hospital
salt loss is reduced—led to new formulations being admissions (0·69, 0·50–0·95). In Bangladesh, Baqui and
developed that contained reduced glucose and sodium colleagues20 reported a 24% reduction in diarrhoea-related
concentrations (table). A meta-analysis17 showed that

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Panel: Strategies for management of acute diarrhoea in Children (%)100
developing countries 90
80 1985 1990 1995 2000 2005 2010
Original oral rehydration solution5 70 Year
• Effective for treatment of 90% of diarrhoea cases 60
50
Reduced osmolarity oral rehydration solution17 40
• Same effectiveness as original oral rehydration solution 30
• Improved safety 20
10
• 20% decrease in stool output
• 30% reduction in vomiting 0
• 40% reduction in the need for unscheduled 1980

intravenous treatment Figure 2: Global percentage of children younger than 5 years with diarrhoea
who received oral rehydration solution
Zinc Data from Olivier Fontaine, WHO, Geneva, Switzerland.
• 12 h mean reduction in duration of acute diarrhoea
Additionally, community programming efforts were
episodes18 confused by inconsistent messages about home-based
• 16 h mean reduction in duration of persistent diarrhoea oral rehydration. Promotion of the original oral solution
became weakened by the suggestion that alternative
episodes18 fluids could be used to prevent dehydration, which led to
• 29% lower relative risk of diarrhoea continuation to the the false assumption that any water-containing liquid
could effectively prevent or treat dehydration. By
7th day18 categorising oral rehydration solution and home fluids as
• 34% decreased frequency of diarrhoea in 2–3 months appropriate treatment, programme monitoring agencies
have given countries a false sense of accomplishment,
after treatment19 because this classification assumes all children receiving
• 51% decrease in overall mortality20 home fluids—irrespective of type of fluid or diarrhoeal
severity—were being properly managed.
hospitalisation rate (95% CI 0·59–0·96). Additionally,
zinc treatment for diarrhoea resulted in an overall UNICEF reports23 that the percentage of children
decrease in mortality (risk ratio 0·49, 95% CI 0·25–0·94). younger than 5 years who received oral solution for
On the basis of the proven safety and effectiveness of diarrhoea from 2005 to 2008 was 29% in Africa, 32% in
zinc supplementation as an adjunct to diarrhoea north Africa and the Middle East, 33% in south Asia, and
treatment, WHO recommends oral zinc for 10–14 days at 38% in east Asia and the Pacific (figure 3). Furthermore,
20 mg per day in children older than 6 months and 10 mg rates often differ within a country: generally being lower
per day in those younger than 6 months for acute in rural and poor populations, where diarrhoea mortality
diarrhoea episodes in developing countries.7 rates are highest, than they are in urban areas.26

Barriers to effective policy implementation Only 31% of doctors prescribed oral rehydration
solution for diarrhoea in a study in India,27 whereas
Since 1995, use of oral rehydration solution has antibiotics or other unnecessary drugs were prescribed to
stagnated in most countries (figure 2). Funding for 79% of patients. Doctors might prescribe medication
diarrhoea-control programmes lessened in the 1990s because the original oral solution did not shorten the
and treatment was incorporated into the integrated duration of illness or reduce the stool output from
management of childhood illness approach promoted diarrhoea, and thus would not be seen as an effective
by WHO and UNICEF. This incorporation led to an treatment. As a result, parents demand additional
immediate reduction in diarrhoea-control activities medications, especially from private practitioners.28
from full country programmes to implementation in Additionally, drugs cost more than oral rehydration
small areas. The approach was initially undertaken in solution does, resulting in increased profit for physicians
only a few districts (and in many countries is still used and pharmacists. Further efforts are needed to improve
in a small proportion of the population).22 As emphasis the education of health-care providers about this
shifted to the integrated management of childhood treatment, ensure a reliable supply for no or low cost
illness approach, training focused on health-facility through the public sector, or make the sale of oral solution
workers, and the community component did not put sufficiently profitable through new financing mechanisms
sufficient emphasis on diarrhoea treatment. Advocacy so that the private sector will promote its use.
groups for other diseases, such as malaria and AIDS
(which result in fewer deaths than does diarrhoea in The promotion of a combination of oral solution with
children younger than 5 years), promoted disease- zinc, which provides effective treatment without un-
specific programmes, resulting in diarrhoeal diseases necessary antibiotics or drug use, could lead to increased
being pushed further down the priority list for national acceptability among caregivers and physicians. With zinc
and international policy makers.22

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≥60%
45–60%
30–45%
15–30%
<15%
No data

Figure 3: Percentage of children with diarrhoea in the previous 2 weeks who received oral rehydration solution
For the latest Demographic and Health Survey and Multiple Indicator Cluster Survey data see references 24 and 25.

and low osmolarity rehydration solution, caregivers can would be even more successful than earlier efforts.21,29
shorten the duration of diarrhoea and prevent future Unfortunately, diarrhoea treatment in many countries is
episodes. Data from a community randomised not a priority. Therefore, we cannot assume that
investigation21 in India comparing oral rehydration diarrhoea treatment will improve simply through
solution and zinc with oral rehydration solution alone introduction of zinc and low osmolarity oral rehydration
showed that communities who were given zinc had solutions to these health systems. National governments
reduced unwarranted care-seeking by 34% (OR 0·66, and donors should recognise the urgent need for new
95% CI 0·43–0·99), oral antibiotic use by 88% (0·12, resources to strengthen health systems for delivery of
0·05–0·32), intravenous fluid use by 50% (0·50, oral rehydration solution and zinc while maintaining an
0·22–1·14), and prescription rates of oral rehydration adequate supply chain and training health workers.
solution increased more than 12-fold (12·46, 8·95–17·35).
Similarly, investigators from a six-site multi-country Diarrhoea mortality rates dropped by 75% from 1980
study29 who gave zinc for diarrhoea treatment noted to 2008,1,9 but remain unacceptably high. New
reductions in antibiotic use in intervention clinics. interventions for treatment (low osmolarity oral
rehydration solution and zinc) and rotavirus vaccines
Although initial introduction of zinc was limited by low for prevention of diarrhoea have provided an opportunity
availability, it is now available through UNICEF and to revitalise diarrhoea-control programmes around the
manufactured in several developing countries. Despite world.31 International agencies, donor communities,
this progress, most countries do not include zinc as part and host countries should put renewed emphasis on
of routine public drug procurement. Additionally, the prevention of unnecessary deaths from this neglected
benefits of zinc are not widely known among doctors, disease that claims the lives of nearly 1·5 million
health-care workers, or pharmacists and, as a result, zinc children every year.
is not given for most cases of diarrhoea.30
Contributors
Intense promotion of oral rehydration solution use at All authors participated in the development, writing, and editing of this
the community level and proper training of health care report.
workers was successful in the 1980s;9,11 there is no reason
that a similar strategy with dual zinc and solution therapy Conflicts of interest
would not be as beneficial now with proper planning, We declare that we have no conflicts of interest.
funding, and coordination with other child survival
strategies. Indeed, evidence suggests that dual promotion Acknowledgments
We thank Olivier Fontaine (WHO, Geneva, Switzerland) for his
contribution of data and valuable insights.

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