REVIEW URRENT C OPINION
Global burden of childhood diarrhea and interventions Jai K. Das a, Rehana A. Salam a, and Zulfiqar A. Bhutta a,b
Purpose of review Diarrhea is a leading cause of morbidity and mortality among children under 5 years in low-income and middle-income countries. Over the past 2 decades under-five mortality has decreased substantially, but reductions have been uneven and unsatisfactory in resource-poor regions. Recent findings There are known interventions which can prevent diarrhea or manage children who suffer from it. Interventions with proven effectiveness at the prevention level include water, sanitation, and hygiene interventions, breastfeeding, complementary feeding, vitamin A and zinc supplementation, and vaccines for diarrhea (rotavirus and cholera). Oral rehydration solution, zinc treatment, continued feeding, and antibiotic treatment for certain strains of diarrhea (cholera, Shigella, and cryptosporidiosis) are effective strategies for treatment of diarrhea. The recent Lancet series using the ’Lives Saved’ tool suggested that if these identified interventions were scaled up to a global coverage to at least 80%, and immunizations to at least 90%; almost all deaths due to diarrhea could be averted. Summary The current childhood mortality burden highlights the need of a focused global diarrhea action plan. The findings suggest that with proper packaging of interventions and delivery platforms, the burden of childhood diarrhea can be reduced to a greater extent. All that is required is greater attention and steps toward right direction. Keywords child mortality, children, diarrhea, global action plan for diarrhea and pneumonia
BACKGROUND
DIARRHEA BURDEN
Child health has been attracting the desired attention for a long time now, and there has been a great deal of progress in terms of bringing collaborations among relevant stakeholders, finding solutions, and setting priorities and targets. Recent international initiatives, such as ‘Every Woman Every Child’, the ‘United Nations Commission on Life-Saving Commodities for Women and Children’, and ‘A Promise Renewed’, have also reinvigorated the child survival agenda. But the job is still far from complete and progress on the ground has been off target generally. Time trends hide the real tragedy because, even in the year 2012, 6.6 million children under the age of 5 years died mostly from preventable causes [1]. Despite the fact that there are known solutions to prevent a majority of these deaths, we have not been able to curtail these deaths. Accelerating the reduction in child deaths will require targeting the leading causes of mortality, which include neonatal and infectious causes [2]; and diarrhea accounts for a tenth of all under five child deaths [1].
In the year 2011, 700 000 children under the age of 5 years did not survive because of complications related to diarrhea. A high proportion of these diarrhea-related deaths occur in the first 2 years of life (72%), highlighting the significance of intervening in this period. Diarrhea incidence peaks at age 6–11 months and then decreases with age; proportionate mortality is highest for age 0–11 months, the ages at which the risk of disease and severe
a Division of Woman and Child Health, Aga Khan University, Karachi, Pakistan and bProgram for Global Pediatric Research, Hospital for Sick Children, Toronto, Ontario, Canada
Correspondence to Zulfiqar A. Bhutta, Founding Director, Center of Excellence in Women and Child Health, Aga Khan University, Karachi 74800, Pakistan and Robert Harding Chair in Global Child Health and Policy, Centre for Global Child Health, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada. Tel: +92 213 493 0051 x4782; fax: +92 213 493 2095; e-mail: [email protected] Curr Opin Infect Dis 2014, 27:451–458 DOI:10.1097/QCO.0000000000000096
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KEY POINTS The risk factors for diarrhea include poverty, undernutrition, poor hygiene, and underprivileged household conditions and poor access to appropriate care. There are known proven interventions which if implemented at scale can go a long way in reducing morbidity and mortality due to diarrhea. Some of these interventions are specific and work either at preventing or treating it, whereas there are generic interventions which work at either improving the environment that the child lives in or improving the child’s nutrition status. There is a need to identify, target, and reach the poorest and hardest-to-reach communities and provide them with better and accessible healthcare. There is a need to build a workforce of front-line health workers who are better trained and supported to deliver quality services to communities, including the prevention and management of diarrhea in the home and community. Future efforts should be directed to strengthen partnerships between public and private actors and continue to lobby governments and other stakeholders to ensure improved and accessible services.
population-based burden of pediatric diarrheal disease in sub-Saharan Africa and south Asia concluded that interventions targeting five pathogens (rotavirus, Shigella, enterotoxigenic Escherichia coli (ETEC), Cryptosporidium, and typical enteropathogenic E coli) can substantially reduce the burden of moderate-tosevere diarrhea in these regions [7]. Multiple episodes per child per year which occur especially in low and middle income countries also lead to nutritional deficits and long-term consequences; an analysis showed that the odds of stunting increase by 1.13 (95% confidence interval (CI): 1.07, 1.19) for every five episodes of diarrhea in children at 2 years of age and these odds were higher for children before 2 years of age [8]. These repeated episodes can also lead to cognitive impairment through stunting [9]. Many of these available data are not nationally representative and do not come from the highest mortality stratum, and so they might underestimate the true national burden of disease [10]. But still, the available figures impose the need to accelerate the progress toward preventing and treating diarrhea and save children, especially those who are underprivileged, undernourished, and living in remote areas.
RISK FACTORS disease also peak [3]. There have been reductions in childhood mortality over the past two decades, but the incidence of diarrhea has shown far less than desired trends. Incidence of diarrhea has decreased from 3.4 episodes per child-year in 1990 to 2.9 episodes per child-year in 2010; and it still remains one of the most common reasons of hospital admission, with an estimated 1731 million episodes of childhood diarrhea reported in 2011 of which 2% progressed to severe disease [1,4 ,5 ]. There is less disparity between regions of the world for the incidence of diarrhea but severity and case-fatality ratios are much higher in low-income than in middleincome and high-income countries. The overall burden of morbidity and mortality of childhood diarrhea is unevenly spread across the world and south-east Asia and Africa share the maximum brunt and nearly three-quarters of diarrhea mortality is concentrated in just 15 high-burden countries (Table 1) [1,4 ,5 ]. Several organisms have been implicated as important causes of these deaths. In a recent review on estimates of pathogen-specific diarrhea mortality among children under the age of 5 years, rotavirus, calicivirus, and enteropathogenic and enterotoxigenic Escherichia coli were found to cause more than half of all diarrheal deaths in children under 5 years of age [6]. The Global Enteric Multicenter Study to identify the cause and &
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The risk factors for diarrhea include poverty, undernutrition, poor hygiene, and underprivileged household conditions which make children more prone to acquire and succumb to diarrhea. These risk factors, which are more prevalent in underprivileged settings, and together with the global uneven distribution of healthcare, make children living in these settings more susceptible [5 ]. Nutrition and infection especially diarrhea are interlinked and either one can lead to other and form a viscous circle; hence, the importance of improving childhood nutrition cannot be underscored. Nutrition risk factors include not exclusively breastfeeding infants younger than 6 months, inappropriate complementary feeding till 2 years of age, and vitamin A and zinc deficiency [11]. Vitamin A deficiency increases the risk of severe diarrhea and thus diarrhea mortality (relative risk (RR): 1.5, 95% CI: 1.3, 1.8) [5 ]. Lack of breastfeeding is associated with a 165% (RR: 2.65, 95% CI: 1.72, 4.07) increase in diarrhea incidence in infants aged 0–5 months and a 32% (RR: 1.32, 95% CI: 1.06, 1.63) increase in infants aged 6–11 months. Lack of breastfeeding is also associated with a 47% (RR: 1.47, 95% CI: 0.67, 3.25) increase in diarrhea-related mortality among infants aged 6–11 months and a 157% (RR: 2.57, 95% CI: 1.10–6.01) increase in infants aged 12–23 months [12]. Risk relations between specific unwashed hands and poor water quality and diarrhea morbidity and mortality have been proven but &&
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Global burden of childhood diarrhea and interventions Das et al. Table 1. 15 High burden countries for childhood diarrhea incidence, severity, and mortality Country
Population 0–4 years (2010)
Incidence (episodes/ child-year)
Total number of episodes (106)
Total number of severe episodes (106)
Total number of deaths (103)
India
127 960 004
2.44 (1.54–3.32)
312.22 (196.67–424.83)
6.74 (4.96–7.90)
205.6 (168.1–266.6)
Nigeria
26 568 927
3.89 (2.67–6.36)
103.35 (70.90–169.02)
2.23 (1.64–2.61)
80.8 (38.4–149.4)
DR Congo
11 848 026
3.47 (2.28–5.38)
41.11 (27.03–63.73)
0.89 (0.65–1.04)
59.9 (30.9–107.9)
Pakistan
21 418 111
3.21 (1.76–4.66)
68.75 (37.79–99.88)
1.48 (1.09–1.74)
37.1 (23.1–57.1)
5 545 968
3.85 (2.24–5.86)
21.35 (12.44–32.48)
0.46 (0.34–0.54)
18.7 (11.4–27.9)
Ethiopia
11 931 668
3.04 (1.84–4.53)
China
81 595 595
2.23 (1.26–2.56)
Afghanistan
Angola
36.27 (22.00–54.10) 181.96 (102.77–208.50)
0.78 (0.58–0.92)
23.7 (12.4–36.4)
3.93 (2.89–4.60)
7.7 (0.7–15.7) 18.0 (9.4–33.6)
3 377 576
3.53 (2.33–5.51)
11.92 (7.88–18.59)
0.26 (0.19–0.30)
21 578 876
2.17 (1.24–3.12)
46.82 (26.66–67.26)
1.01 (0.74–1.18)
6.8 (4.7–10.1)
Kenya
6 664 323
2.80 (1.60–4.10)
18.66 (10.68–27.31)
0.40 (0.30–0.47)
9.5 (5.3–15.0)
Burkina Faso
2 955 148
3.51 (2.32–5.47)
10.37 (6.86–16.15)
0.22 (0.16–0.26)
11.6 (6.9–19.4)
Indonesia
Uganda
6 465 275
3.26 (2.06–4.93)
21.08 (13.30–31.88)
0.46 (0.34–0.53)
12.2 (7.2–17.6)
Niger
3 084 517
3.96 (2.74–6.55)
12.21 (8.44–20.20)
0.26 (0.19–0.31)
12.4 (6.6–20.3)
Mali
2 911 668
3.96 (2.74–6.55)
11.53 (7.97–19.08)
0.25 (0.18–0.29)
17.2 (8.4–33 0.7)
Tanzania
8 009 544
3.01 (1.81–4.47)
24.10 (14.49–35.79)
0.52 (0.38–0.61)
9.9 (6.2–13.8)
Reproduced from [5
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there is not enough evidence on in appropriate excreta disposal [13].
INTERVENTIONS There are known proven interventions which if implemented at scale can go a long way in reducing
morbidity and mortality due to diarrhea. Some of these interventions are specific and work either at preventing or treating it, whereas there are generic interventions which work at either improving the environment that the child lives in or improving the child’s nutrition status (Fig. 1) The new era of vaccines also offers great hope as nearly a third
Environmental Water, sanitation, hygiene, hand washing, overcrowding
Increased susceptibility
Nutrition
Delivery platforms
Breastfeeding, complementary feeding, preventive vitaminA/ zinc supplementation
Vaccines
Community-based health and behavior change promotion
Exposure
Rotavirus, cholera
Financial incentives to promote care seeking Integrated community case management
Treatment ORS , continued feeding, zinc, probiotics, antibiotics for dysentery
Diarrhea
Survival
Facility-based integrated management of childhood illnesses
Death
FIGURE 1. Interventions for prevention and treatment of diarrhea. Modified with permission from [40 ]. &&
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of episodes of severe diarrhea are preventable by vaccination (i.e., against rotavirus and cholera) [5 ]. These vaccines together with the provision of essential commodities [oral rehydration solution (ORS), zinc] can greatly impact child survival. Described below and in Table 2 are these effective interventions.
soap, improved water quality, and excreta disposal, respectively [13].
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Water provision or use, sanitation, and hygiene A review evaluated the effectiveness of water, sanitation, and hygiene interventions and concluded that water quality interventions (protection or treatment of water at source or point of use) were more effective than interventions to improve water supply (improved source of water and/or improved distribution) [14]. Water quality interventions are associated with a 42% relative reduction in child diarrhea morbidity. Overall sanitation and hygiene interventions lead to an estimated 37 and 31% reduction in child diarrhea morbidity, respectively. A recent review estimated risk reductions for diarrhea of 48, 17, and 36%, with hand washing with
Breastfeeding Initiation of breastfeeding within 1 h of birth, exclusive breastfeeding of infants till 6 months of age, and continued breastfeeding till 2 years of age or longer are recommended [15]. Improved breastfeeding rates are related to reduced diarrhea morbidity and mortality. Breastfeeding initiation within 24 h of birth is associated with a 44–45% reduction in allcause and infection-related neonatal mortality [16], and is thought to mainly operate through the effects of exclusive breastfeeding. Breastfeeding educational and promotional interventions lead to an improvement in exclusive breastfeeding rates (by 43% at 1 day, 30% for 0–1 month, and 90% for 1–6 months age). Correspondingly, rates of ‘not breastfeeding’ also decrease significantly by 32% at 1 day, 30% for 0–1 month, and 18% for 1–6 months [17 ]. Beyond 6 months, educational interventions lead to increase rates of partial breastfeeding by 19%. These findings call for strategies to promote and scale up &
Table 2. Interventions and impacts (with 95% confidence interval) Intervention
Effect estimate
Water, sanitation, and hygiene
48, 17, and 36% risk reductions for diarrhea with hand washing with soap, improved water quality, and excreta disposal, respectively.
Breast feeding education
Educational or counseling interventions increased exclusive breastfeeding rates by 43% (95% CI: 9%-87%) at day 1, by 30% (19–42%) till 1 month, and by 90% (54%, 134%) from 1–6 months. Significant reductions in rates of ‘no breastfeeding’ were also observed; 32% (13%, 46%) at day 1, 30% (20%, 38%) 0–1 month, and 18% (11%, 23%) for 1–6 months.
Preventive zinc supplementation
Diarrhea incidence reduces by 13% (6%, 19%), but no significant impact on mortality.
Vaccines for rotavirus
74% (35–90%) effective against very severe rotavirus infection, 61% (38–75%) against severe rotavirus infection, and hospitalization reduced by 47% (22–64%).
Vaccines for cholera
52% (36%, 65%) effective against cholera infection. Vibriocidal antibodies increased by 124% (32%, 280%).
ORS and RHF
Use of ORS reduced diarrhea-specific mortality by 69% (51–80%) and treatment failure to 0.2% (0.1–0.2%). Limited evidence for the benefit of recommended home fluids.
Dietary management of diarrhea
Lactose-free diets reduce the duration of diarrhea treatment failure significantly by 47% (30%, 60%) and reduce the duration of diarrhea.
Therapeutic zinc supplementation
Reduces all-cause mortality by 46% (12%, 68%) and diarrhea hospitalization by 23% (15%, 31%) but has nonsignificant reduction in diarrhea-specific mortality.
Antibiotics for cholera
63% (29%, 81%) reduction in clinical failure rates and 75% (47%, 88%) reduction in bacteriological failure rates.
Antibiotics for Shigella
Clinical failure rates reduced by 82% (67%, 90%) and bacteriological failure by 96% (88%, 99%).
Antibiotics for cryptosporidiosis
There was a 52% (25%, 70%) reduction in clinical failure rates, and 38% (17%, 54%) reduction in parasitological rates.
Community-based interventions
Community-based interventions are associated with a significant increase in the use of ORS by 160% (60%, 327%) and 80% increase in the use of zinc in diarrhea (67). There was 9% (6%, 11%) increase in care seeking for diarrhea and a 75% (49%, 88%) decline in inappropriate use of antibiotics for diarrhea.
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Global burden of childhood diarrhea and interventions Das et al.
breastfeeding, but there is limited evidence to address the issues of barriers around work environments and supportive strategies such as the provision of maternity leave.
Preventive zinc and vitamin A supplementation About 17.3% of the world’s population is zinc deficient and this is most prevalent in children under 5 years of age in developing countries [18]. Preventive zinc supplementation has no impact on all-cause or diarrhea-specific mortality but leads to a 13% reduction (RR: 0.87; 95% CI: 0.81, 0.94) in the incidence of diarrhea [19]. Vitamin A supplementation is associated with a 28% reduction (RR: 0.72; 95% CI: 0.57, 0.91) in diarrhea-specific mortality and 15% (RR: 0.85; 95% CI: 0.82, 0.87) reduced incidence of diarrhea [20].
Vaccines Rotavirus is the most common cause of severe dehydrating diarrhea in young children globally [5 ]. Newer rotavirus vaccines are associated with reduction in very severe and severe rotavirus infections by 74 (95% CI: 35,90) and 61% (95% CI: 38,75), respectively and rotavirus-related hospitalization among young children by 47% (95% CI: 22, 64), although there are geographic variations observed in vaccine effectiveness [21]. Another important vaccine is for cholera. Although case management with ORS has substantially improved cholera case fatality rates, the disease can still kill rapidly, especially in outbreak settings [22]. Oral cholera vaccine reduces the risk of cholera infection in children under 5 years of age by 52% (RR: 0.48; 95% CI: 0.35, 0.64) [23 ]. This evidence for the effectiveness of oral cholera vaccine makes them a good candidate for the control of cholera in endemic areas and recent research indicates that because of herd protection, even moderate coverage levels of targeted populations with oral vaccine have the potential to lead to almost complete control of cholera [24–26], although this would not prevent outbreaks in other populations. Findings from a recent review on the economic value of diarrheal vaccines suggest that there is an evidence of the economic benefits of rotavirus and cholera vaccines in specific contexts [27]. There are newer vaccines available for Shigella and ETEC although they are not currently recommended. Limited evidence does suggest efficacy of Shigella vaccine against S. flexneri infection at 28% and for S. Sonnei at 53% [23 ]. Despite these initial promising data, there are no vaccines currently available and none &&
&
&
in the pipeline for Shigella and ETEC in the near future.
Therapeutic interventions Interventions for the treatment of diarrhea include ORS, continued feeding, zinc, and antibiotics in some cases. Because the immediate cause of death in most cases of diarrhea is dehydration, the majority of diarrhea deaths can be prevented if dehydration is managed appropriately. ORS and recommended home fluids reduce diarrhea-specific mortality by 69% (95% CI: 51,80%) [28]. Since 2004, zinc is recommended for the treatment of diarrhea and it is associated with a significant reduction in all-cause mortality by 46% (RR 0.54; 95% CI: 0.32, 0.88) and diarrhea-related hospitalizations by 23% (RR: 0.77; 95% CI: 0.69, 0.85) [29]. Current guidelines on the management and treatment of diarrhea in children strongly recommend continued feeding alongside the administration of ORS and zinc therapy. However, there is some debate regarding the optimal diet or dietary ingredients for hastening recovery and maintaining nutritional status in children with diarrhea. An extensive review of feeding strategies and food-based interventions found that the illness duration was shorter and treatment failure risk lower among children with acute diarrheaconsuming lactose-free rather than lactose-containing liquid feeds, no effect of lactose avoidance was shown for stool output or weight gain [30]. It further suggested that locally available ingredients can be used to manage childhood diarrhea as effectively as commercial preparations or specialized ingredients [30]. Antibiotics are also used to treat some forms of bacterial diarrhea especially dysentery. A review [31] evaluated the effectiveness of WHO recommended antibiotics – ciprofloxacin, ceftriaxone, and pivmecillinam for the treatment of dysentery and concluded that antibiotics are effective in reducing the clinical and bacteriological signs and symptoms of dysentery and thus can be expected to decrease diarrhea mortality attributable to dysentery by more than 99%. A review evaluated the effectiveness of antibiotics in diarrhea due to cholera, Shigella, and Cryptosporidium infections [32 ]. The mainstay of therapy in cholera is rehydration, although antibiotics are recommended for severe cases and evidence suggests that antibiotic resulted in a 63% reduction (RR 0.37; 95% CI: 0.19, 0.71) in clinical failure rates whereas bacteriological failure rates were reduced by 75% (RR: 0.25; 95% CI: 0.12, 0.53) [32 ]. Antibiotic management of Shigella results in 82% reduction (RR 0.18; 95% CI: 0.10, 0.33) in clinical failure and a 96% reduction (RR 0.04; 95% CI: 0.01, 0.12) in bacteriological failure
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rates [32 ]. Cryptosporidium may cause life-threatening disease particularly in people who are immunecompromised and contributes significantly to morbidity among children. Evidence shows that antibiotics for the treatment of cryptosporidiosis in immuno-competent patients reduce clinical failure rates by 52% (RR 0.48; 95% CI: 0.30, 0.75), whereas parasitological failure rates are reduced by 38% (RR 0.62; 95% CI: 0.46, 0.83) [32 ]. Other newer and potential interventions to manage diarrhea include probiotics and antiemetics. Probiotics are becoming increasingly popular treatments for diarrhea in some countries. A review undertaken to evaluate the effectiveness of probiotics estimated a 14% reduction in diarrhea duration [33 ]. Despite being a subject of controversy, a number of anti-emetic agents are now commonly administered worldwide in an attempt to reduce vomiting in the proportion of children presenting with acute gastroenteritis and vomiting. A review found that administration of ondansetron reduces the incidence of vomiting and hospitalization by 54% and the requirement for intravenous infusions by 60%. Antiemetics may be of potential benefit in the subset of cases of acute diarrhea with associated severe vomiting precluding oral rehydration. &
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IMPROVING ACCESS Despite knowing what to do to prevent deaths in children due to diarrhea, we are still lagging behind because most of these interventions have low coverage globally and more in low- and middle-income countries (Fig. 2) [34]. There is little consensus
about the strategies to safeguard delivery of these interventions to reduce disparities and provide equitable access to marginalized populations. Increasing access to high-quality treatment is a priority to reduce deaths. The Integrated Management of Childhood Illnesses [35] approach in health facilities has improved the quality of clinical care. Integrated community case management [36] of pneumonia, diarrhea, and malaria improves access to care, and community health workers can safely and effectively treat diarrhea. Community-based interventions through home visits and community-based sessions for education and promotion of care seeking are effective and cost-effective and can play a major role in improving the coverage of essential interventions. The role of community health workers has been evaluated in various settings in large-scale programs and demonstrated to improve immunization uptake and care seeking for childhood illnesses [37]. A review evaluated the effect of community-based delivery strategies on the coverage and uptake of essential commodities for diarrhea [38 ]. It estimated that these strategies are associated with a 160% (RR: 2.60; 95% CI: 1.59, 4.27) increase in the use of ORS and an 80% increase in the use of zinc in diarrhea [38 ]. There was also a 9% (RR: 1.09; 95% CI: 1.06, 1.11) increase in care seeking and a 75% (RR: 0.25; 95% CI: 0.12, 0.51) decline in the inappropriate use of antibiotics for diarrhea. Financial incentives are also becoming widely used policy strategies to alleviate poverty, promote care seeking, and improve the health of populations. Apart from improving the coverage of the interventions, efforts should also be directed toward improving the quality of clinicbased and community-based care, and new &
&
100.00 90.00
Coverage (%)
80.00 70.00 60.00 50.00 40.00 30.00 20.00 10.00 Use of improved water source
Vitamin A supplementation
Hygienic disposal of children's stools
Improved excreta disposal
ORS
Antibiotics for dysentery
Water connection at home
Hand washing with soap
Exclusive breastfeeding (1-6 month)
Zinc for diarrhrea treatment
Rotavirus vaccine
0.00
FIGURE 2. Coverage of interventions for 75 countdown countries (median with interquartile range). Reproduced from [40 ]. &&
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Global burden of childhood diarrhea and interventions Das et al.
approaches to enhance quality and accessibility of care should continue to be assessed [39].
DISCUSSION The recent Lancet series using the ‘Lives Saved’ tool suggested that if these identified interventions were scaled up to a global coverage to at least 80%, and immunizations to at least 90%; almost all diarrhea deaths could be eliminated [40 ]. Yet, the rate of adoption of these interventions is highly variable and often slow, especially in settings with the greatest need. But global and national attention to childhood diarrhea has been sorely lacking despite the need for it to assume a more prominent position on the child survival agenda given its substantial contribution to child mortality [34], although, recently, there have been efforts to bring it on the radar of national governments and international agencies. The Global Action Plan for Diarrhea and Pneumonia (GAPPD) was launched in April 2013, with an aim to end all preventable deaths, fewer than three deaths per 1000 live births from pneumonia and less than one death per 1000 live births from diarrhea by the year 2025 [41 ]. These targets are plausible especially when we know what works and how. What is required foremost is greater political will and long-term commitment to ensure all children have access to essential treatments such as ORS and zinc for diarrhea, on-time infant vaccination, breastfeeding and high-quality early childhood nutrition with improvement in rates of care-seeking and appropriate case management. In parallel, attention on management, human resources, commodities, programming monitoring and data feedback are required, as well as resources commensurate with the magnitude of the challenge. There is a need to develop clear a country-level strategy and work plan, with key responsibilities assigned. There is also a need for inter-sectoral action transparency and good governance for the effective implementation of the adopted policies. Should we choose to do so, morbidity and mortality due to diarrhea can be alleviated. The role of academia and research cannot be undermined and will continue to play a central role in the development of new vaccines, finding solutions to antibiotic resistance, threats posed by climate change and also to finding ways to improve access to care and improve quality of care and creating demand and supply.
extent. The new integrated GAPPD will guide international efforts to prevent children dying from diarrhea. The efforts will require strong national political backing, the setting of clear priorities, and long-term financial investment. The results we can achieve will repay the effort and beyond. Acknowledgements None.
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CONCLUSION The findings suggest that with proper packaging of interventions and delivery platforms; the burden of childhood diarrhea can be reduced to a greater
Conflicts of interest There are no conflicts of interest.
REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest && of outstanding interest 1. UNICEF: Levels & Trends in Child Mortality, Estimates Developed by the UN Inter-agency Group for Child Mortality Estimation. New York, NY: UNICEF; 2013. Available at http://www.childinfo.org/files/Child_Mortality_Report_ 2013.pdf 2. Liu L, Johnson HL, Cousens S, et al., Child Health Epidemiology Reference Group of WHO and UNICEF. Global, regional, and national causes of child mortality: an updated systematic analysis for 2010 with time trends since 2000. Lancet 2012; 379:2151–2161. 3. Fischer-Walker CL, Perin J, Aryee MJ, et al. Diarrhea incidence in low- and middle-income countries in 1990 and 2010: a systematic review. BMC Public Health 2012; 12:220. 4. Black RE, Victora CG, Walker SP, et al. Maternal and child undernutrition and & overweight in low-income and middle-income countries. Lancet 2013; 382:427–451. A recent study highlighting the current burden, trends, and risk factors of undernutrition globally. 5. Walker CL, Rudan I, Liu L, et al. Global burden of childhood pneumonia and && diarrhoea. Lancet 2013; 381:1405–1416. A thorough review of the current burden, distribution, and risk factors of diarrhea and pneumonia in children globally. 6. Lanata CF, Fischer-Walker CL, Olascoaga AC, et al. Global causes of diarrheal disease mortality in children < 5 years of age: a systematic review. PLoS One 2013; 8:e72788. 7. Kotloff KL, Nataro JP, Blackwelder WC, et al. Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study. Lancet 2013; 382:209–222. 8. Checkley W, Buckley G, Gilman RH, et al. Multicountry analysis of the effects of diarrhoea on childhood stunting. Int J Epidemiol 2008; 37:816–830. 9. Fischer-Walker CL, Lamberti L, Adair L, et al. Does childhood diarrhea influence cognition beyond the diarrhea-stunting pathway. PLoS One 2012; 7:e47908. 10. Rudan I, El Arifeen S, Black RE, Campbell H. Childhood pneumonia and diarrhoea: setting our priorities right. Lancet Infect Dis 2007; 7:56–61. 11. Bhutta ZA, Das JK. Global burden of childhood diarrhea and pneumonia: what can and should be done? Pediatrics 2013; 131:634–636. 12. Lamberti L, Walker CF, Noiman A, et al. Breastfeeding and the risk for diarrhea morbidity and mortality. BMC Public Health 2011; 11 (Suppl 3):S15. 13. Cairncross S, Hunt C, Boisson S, et al. Water, sanitation and hygiene for the prevention of diarrhoea. Int J Epidemiol 2010; 39 (Suppl 1):i193–i205. 14. Waddington H, Snilstveit B, White H, Fewtrell L. Water, sanitation and hygiene interventions to combat childhood diarrhoea in developing countries. International Initiative for Impact Evaluation New Delhi 2009. 15. World Health Organization. The optimal duration of exclusive breastfeeding: report of an expert consultation. Geneva, Switzerland; 28–30 March 2001 Available from: http://www.who.int/nutrition/publications/infantfeeding/WHO_ NHD_01.09/en/index.html. [Accessed 28 March 2014] 16. Debes AK, Kohli A, Walker N, et al. Time to initiation of breastfeeding and neonatal mortality and morbidity: a systematic review. BMC Public Health 2013; 13 (Suppl 3):S19. 17. Haroon S, Das JK, Salam RA, et al. Breastfeeding promotion interventions and & breastfeeding practices: a systematic review. BMC Public Health 2013; 13 (Suppl 3):S20. A thorough review of the strategies which could augment the breastfeeding practices.
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Gastrointestinal infections 18. Das JK, Kumar R, Salam RA, Bhutta ZA. Systematic review of zinc fortification trials. Ann Nutr Metab 2013; 62 (Suppl 1):44–56. 19. Yakoob MY, Theodoratou E, Jabeen A, et al. Preventive zinc supplementation in developing countries: impact on mortality and morbidity due to diarrhea, pneumonia and malaria. BMC Public Health 2011; 11 (Suppl 3):S23. 20. Imdad A, Herzer K, Mayo-Wilson E, et al. Vitamin A supplementation for preventing morbidity and mortality in children from 6 months to 5 years of age. Cochrane Database Syst Rev 2010; Issue 12. Art. No.: CD008524. 21. Munos MK, Walker CLF, Black RE. The effect of rotavirus vaccine on diarrhoea mortality. Int J Epidemiol 2010; 39 (Suppl 1):i56–i62. 22. Piarroux R, Barrais R, Faucher B, et al. Understanding the cholera epidemic, Haiti. Emerg Infect Dis 2011; 17:1161–1168. 23. Das JK, Tripathi A, Ali A, et al. Vaccines for the prevention of diarrhea due & to cholera, Shigella, ETEC and rotavirus. BMC Public Health 2013; 13 (Suppl 3):S11. A timely review for prevention of diarrhea through vaccines – both established vaccines and emerging ones. 24. Ali M, Emch M, von Seidlein L, et al. Herd immunity conferred by killed oral cholera vaccines in Bangladesh: a reanalysis. Lancet 2005; 366:44–49. 25. Longini IM Jr, Nizam A, Ali M, et al. Controlling endemic cholera with oral vaccines. PLoS Med 2007; 4:e336. 26. Luquero FJ, Grout L, Ciglenecki I, et al. Use of vibrio cholerae vaccine in an outbreak in Guinea. N Engl J Med 2014; 370:2111–2120. 27. Rheingans R, Amaya M, Anderson JD, et al. Systematic review of the economic value of diarrheal vaccines. Hum Vaccin Immunother 2014; 10: [Epub ahead of print]. 28. Munos MK, Walker CL, Black RE. The effect of oral rehydration solution and recommended home fluids on diarrhoea mortality. Int J Epidemiol 2010; 39 (Suppl 1):i75–87. 29. Walker CLF, Black RE. Zinc for the treatment of diarrhoea: effect on diarrhoea morbidity, mortality and incidence of future episodes. Int J Epidemiol 2010; 39 (Suppl 1):i63–i69. 30. Gaffey MF, Wazny K, Bassani DG, Bhutta ZA. Dietary management of childhood diarrhea in low- and middle-income countries: a systematic review. BMC Public Health 2013; 13 (Suppl 3):S17. 31. Traa BS, Walker CL, Munos M, Black RE. Antibiotics for the treatment of dysentery in children. Int J Epidemiol 2010; 39 (Suppl 1):i70–i74. 32. Das JK, Ali A, Salam RA, Bhutta ZA. Antibiotics for the treatment of cholera, & Shigella and Cryptosporidium in children. BMC Public Health 2013; 13 (Suppl 3):S10. A current quantitative review for the effect of antibiotics for treatment of three important causes of diarrhea.
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33. Applegate JA, Walker CLF, Ambikapathi R, Black RE. Systematic review of probiotics for the treatment of community-acquired acute diarrhea in children. BMC Public Health 2013; 13 (Suppl 3):S16. A timely systematic review of an emerging intervention for managing diarrhea. 34. UNICEF 2012. Pneumonia and diarrhoea. Tackling the deadliest diseases for the world’s poorest children. United Nations Children’s Fund. New York Available at http://www.childinfo.org/files/Pneumonia_Diarrhoea_2012.pdf [Accessed March 2014] 35. WHO. Integrated Management of Childhood Illness (IMCI). http://www.who. int/maternal_child_adolescent/topics/child/imci/en/index.html [Accessed 27 March 2014] 36. Young M, Wolfheim C, Marsh DR, Hammamy D. World Health Organization/ United Nations Children’s Fund joint statement on integrated community case management: an equity-focused strategy to improve access to essential treatment services for children. Am J Trop Med Hyg 2012; 87 (Suppl 5): 6–10. 37. Bhutta ZA, Lassi ZS, Pariyo G. Global experience of community health workers for delivery of health related Millennium Development Goals: a systematic review, country case studies, and recommendations for integration into national health systems. Geneva, WHO/Global Health Workforce Alliance 2010. 38. Das JK, Lassi ZS, Salam RA, Bhutta ZA. Effect of community based & interventions on childhood diarrhea and pneumonia: uptake of treatment modalities and impact on mortality. BMC Public Health 2013; 13 (Suppl 3):S29. A systematic review of the community based interventions which could improve the coverage of essential interventions especially in under resourced settings. 39. Gill CJ, Young M, Schroder K, et al. Bottlenecks, barriers, and solutions: results from multicountry consultations focused on reduction of childhood pneumonia and diarrhoea deaths. Lancet 2013; 381:1487–1498. 40. Bhutta ZA, Das JK, Walker N, et al. Interventions to address deaths from && childhood pneumonia and diarrhoea equitably: what works and at what cost? Lancet 2013; 381:1417–1429. A comprehensive review of existing interventions and delivery platforms with the potential impact of scale up in high burden countries. 41. WHO. Ending Preventable Child Deaths from Pneumonia and Diarrhoea by && 2025 The integrated Global Action Plan for Pneumonia and Diarrhoea (GAPPD). World Health Organization/The United Nations Children’s Fund (UNICEF) 2013. http://apps.who.int/iris/bitstream/10665/79200/1/ 9789241505239_eng.pdf. [Accessed 10 March 2014] A global action plan which apart from bringing in the desired attention also gives the direction to tackle childhood diarrhea. &
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Global burden of childhood diarrhea and interventions Jai K. Das a, Rehana A. Salam a, and Zulfiqar A. Bhutta a,b
Purpose of review Diarrhea is a leading cause of morbidity and mortality among children under 5 years in low-income and middle-income countries. Over the past 2 decades under-five mortality has decreased substantially, but reductions have been uneven and unsatisfactory in resource-poor regions. Recent findings There are known interventions which can prevent diarrhea or manage children who suffer from it. Interventions with proven effectiveness at the prevention level include water, sanitation, and hygiene interventions, breastfeeding, complementary feeding, vitamin A and zinc supplementation, and vaccines for diarrhea (rotavirus and cholera). Oral rehydration solution, zinc treatment, continued feeding, and antibiotic treatment for certain strains of diarrhea (cholera, Shigella, and cryptosporidiosis) are effective strategies for treatment of diarrhea. The recent Lancet series using the ’Lives Saved’ tool suggested that if these identified interventions were scaled up to a global coverage to at least 80%, and immunizations to at least 90%; almost all deaths due to diarrhea could be averted. Summary The current childhood mortality burden highlights the need of a focused global diarrhea action plan. The findings suggest that with proper packaging of interventions and delivery platforms, the burden of childhood diarrhea can be reduced to a greater extent. All that is required is greater attention and steps toward right direction. Keywords child mortality, children, diarrhea, global action plan for diarrhea and pneumonia
BACKGROUND
DIARRHEA BURDEN
Child health has been attracting the desired attention for a long time now, and there has been a great deal of progress in terms of bringing collaborations among relevant stakeholders, finding solutions, and setting priorities and targets. Recent international initiatives, such as ‘Every Woman Every Child’, the ‘United Nations Commission on Life-Saving Commodities for Women and Children’, and ‘A Promise Renewed’, have also reinvigorated the child survival agenda. But the job is still far from complete and progress on the ground has been off target generally. Time trends hide the real tragedy because, even in the year 2012, 6.6 million children under the age of 5 years died mostly from preventable causes [1]. Despite the fact that there are known solutions to prevent a majority of these deaths, we have not been able to curtail these deaths. Accelerating the reduction in child deaths will require targeting the leading causes of mortality, which include neonatal and infectious causes [2]; and diarrhea accounts for a tenth of all under five child deaths [1].
In the year 2011, 700 000 children under the age of 5 years did not survive because of complications related to diarrhea. A high proportion of these diarrhea-related deaths occur in the first 2 years of life (72%), highlighting the significance of intervening in this period. Diarrhea incidence peaks at age 6–11 months and then decreases with age; proportionate mortality is highest for age 0–11 months, the ages at which the risk of disease and severe
a Division of Woman and Child Health, Aga Khan University, Karachi, Pakistan and bProgram for Global Pediatric Research, Hospital for Sick Children, Toronto, Ontario, Canada
Correspondence to Zulfiqar A. Bhutta, Founding Director, Center of Excellence in Women and Child Health, Aga Khan University, Karachi 74800, Pakistan and Robert Harding Chair in Global Child Health and Policy, Centre for Global Child Health, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada. Tel: +92 213 493 0051 x4782; fax: +92 213 493 2095; e-mail: [email protected] Curr Opin Infect Dis 2014, 27:451–458 DOI:10.1097/QCO.0000000000000096
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KEY POINTS The risk factors for diarrhea include poverty, undernutrition, poor hygiene, and underprivileged household conditions and poor access to appropriate care. There are known proven interventions which if implemented at scale can go a long way in reducing morbidity and mortality due to diarrhea. Some of these interventions are specific and work either at preventing or treating it, whereas there are generic interventions which work at either improving the environment that the child lives in or improving the child’s nutrition status. There is a need to identify, target, and reach the poorest and hardest-to-reach communities and provide them with better and accessible healthcare. There is a need to build a workforce of front-line health workers who are better trained and supported to deliver quality services to communities, including the prevention and management of diarrhea in the home and community. Future efforts should be directed to strengthen partnerships between public and private actors and continue to lobby governments and other stakeholders to ensure improved and accessible services.
population-based burden of pediatric diarrheal disease in sub-Saharan Africa and south Asia concluded that interventions targeting five pathogens (rotavirus, Shigella, enterotoxigenic Escherichia coli (ETEC), Cryptosporidium, and typical enteropathogenic E coli) can substantially reduce the burden of moderate-tosevere diarrhea in these regions [7]. Multiple episodes per child per year which occur especially in low and middle income countries also lead to nutritional deficits and long-term consequences; an analysis showed that the odds of stunting increase by 1.13 (95% confidence interval (CI): 1.07, 1.19) for every five episodes of diarrhea in children at 2 years of age and these odds were higher for children before 2 years of age [8]. These repeated episodes can also lead to cognitive impairment through stunting [9]. Many of these available data are not nationally representative and do not come from the highest mortality stratum, and so they might underestimate the true national burden of disease [10]. But still, the available figures impose the need to accelerate the progress toward preventing and treating diarrhea and save children, especially those who are underprivileged, undernourished, and living in remote areas.
RISK FACTORS disease also peak [3]. There have been reductions in childhood mortality over the past two decades, but the incidence of diarrhea has shown far less than desired trends. Incidence of diarrhea has decreased from 3.4 episodes per child-year in 1990 to 2.9 episodes per child-year in 2010; and it still remains one of the most common reasons of hospital admission, with an estimated 1731 million episodes of childhood diarrhea reported in 2011 of which 2% progressed to severe disease [1,4 ,5 ]. There is less disparity between regions of the world for the incidence of diarrhea but severity and case-fatality ratios are much higher in low-income than in middleincome and high-income countries. The overall burden of morbidity and mortality of childhood diarrhea is unevenly spread across the world and south-east Asia and Africa share the maximum brunt and nearly three-quarters of diarrhea mortality is concentrated in just 15 high-burden countries (Table 1) [1,4 ,5 ]. Several organisms have been implicated as important causes of these deaths. In a recent review on estimates of pathogen-specific diarrhea mortality among children under the age of 5 years, rotavirus, calicivirus, and enteropathogenic and enterotoxigenic Escherichia coli were found to cause more than half of all diarrheal deaths in children under 5 years of age [6]. The Global Enteric Multicenter Study to identify the cause and &
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The risk factors for diarrhea include poverty, undernutrition, poor hygiene, and underprivileged household conditions which make children more prone to acquire and succumb to diarrhea. These risk factors, which are more prevalent in underprivileged settings, and together with the global uneven distribution of healthcare, make children living in these settings more susceptible [5 ]. Nutrition and infection especially diarrhea are interlinked and either one can lead to other and form a viscous circle; hence, the importance of improving childhood nutrition cannot be underscored. Nutrition risk factors include not exclusively breastfeeding infants younger than 6 months, inappropriate complementary feeding till 2 years of age, and vitamin A and zinc deficiency [11]. Vitamin A deficiency increases the risk of severe diarrhea and thus diarrhea mortality (relative risk (RR): 1.5, 95% CI: 1.3, 1.8) [5 ]. Lack of breastfeeding is associated with a 165% (RR: 2.65, 95% CI: 1.72, 4.07) increase in diarrhea incidence in infants aged 0–5 months and a 32% (RR: 1.32, 95% CI: 1.06, 1.63) increase in infants aged 6–11 months. Lack of breastfeeding is also associated with a 47% (RR: 1.47, 95% CI: 0.67, 3.25) increase in diarrhea-related mortality among infants aged 6–11 months and a 157% (RR: 2.57, 95% CI: 1.10–6.01) increase in infants aged 12–23 months [12]. Risk relations between specific unwashed hands and poor water quality and diarrhea morbidity and mortality have been proven but &&
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Global burden of childhood diarrhea and interventions Das et al. Table 1. 15 High burden countries for childhood diarrhea incidence, severity, and mortality Country
Population 0–4 years (2010)
Incidence (episodes/ child-year)
Total number of episodes (106)
Total number of severe episodes (106)
Total number of deaths (103)
India
127 960 004
2.44 (1.54–3.32)
312.22 (196.67–424.83)
6.74 (4.96–7.90)
205.6 (168.1–266.6)
Nigeria
26 568 927
3.89 (2.67–6.36)
103.35 (70.90–169.02)
2.23 (1.64–2.61)
80.8 (38.4–149.4)
DR Congo
11 848 026
3.47 (2.28–5.38)
41.11 (27.03–63.73)
0.89 (0.65–1.04)
59.9 (30.9–107.9)
Pakistan
21 418 111
3.21 (1.76–4.66)
68.75 (37.79–99.88)
1.48 (1.09–1.74)
37.1 (23.1–57.1)
5 545 968
3.85 (2.24–5.86)
21.35 (12.44–32.48)
0.46 (0.34–0.54)
18.7 (11.4–27.9)
Ethiopia
11 931 668
3.04 (1.84–4.53)
China
81 595 595
2.23 (1.26–2.56)
Afghanistan
Angola
36.27 (22.00–54.10) 181.96 (102.77–208.50)
0.78 (0.58–0.92)
23.7 (12.4–36.4)
3.93 (2.89–4.60)
7.7 (0.7–15.7) 18.0 (9.4–33.6)
3 377 576
3.53 (2.33–5.51)
11.92 (7.88–18.59)
0.26 (0.19–0.30)
21 578 876
2.17 (1.24–3.12)
46.82 (26.66–67.26)
1.01 (0.74–1.18)
6.8 (4.7–10.1)
Kenya
6 664 323
2.80 (1.60–4.10)
18.66 (10.68–27.31)
0.40 (0.30–0.47)
9.5 (5.3–15.0)
Burkina Faso
2 955 148
3.51 (2.32–5.47)
10.37 (6.86–16.15)
0.22 (0.16–0.26)
11.6 (6.9–19.4)
Indonesia
Uganda
6 465 275
3.26 (2.06–4.93)
21.08 (13.30–31.88)
0.46 (0.34–0.53)
12.2 (7.2–17.6)
Niger
3 084 517
3.96 (2.74–6.55)
12.21 (8.44–20.20)
0.26 (0.19–0.31)
12.4 (6.6–20.3)
Mali
2 911 668
3.96 (2.74–6.55)
11.53 (7.97–19.08)
0.25 (0.18–0.29)
17.2 (8.4–33 0.7)
Tanzania
8 009 544
3.01 (1.81–4.47)
24.10 (14.49–35.79)
0.52 (0.38–0.61)
9.9 (6.2–13.8)
Reproduced from [5
&&
].
there is not enough evidence on in appropriate excreta disposal [13].
INTERVENTIONS There are known proven interventions which if implemented at scale can go a long way in reducing
morbidity and mortality due to diarrhea. Some of these interventions are specific and work either at preventing or treating it, whereas there are generic interventions which work at either improving the environment that the child lives in or improving the child’s nutrition status (Fig. 1) The new era of vaccines also offers great hope as nearly a third
Environmental Water, sanitation, hygiene, hand washing, overcrowding
Increased susceptibility
Nutrition
Delivery platforms
Breastfeeding, complementary feeding, preventive vitaminA/ zinc supplementation
Vaccines
Community-based health and behavior change promotion
Exposure
Rotavirus, cholera
Financial incentives to promote care seeking Integrated community case management
Treatment ORS , continued feeding, zinc, probiotics, antibiotics for dysentery
Diarrhea
Survival
Facility-based integrated management of childhood illnesses
Death
FIGURE 1. Interventions for prevention and treatment of diarrhea. Modified with permission from [40 ]. &&
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of episodes of severe diarrhea are preventable by vaccination (i.e., against rotavirus and cholera) [5 ]. These vaccines together with the provision of essential commodities [oral rehydration solution (ORS), zinc] can greatly impact child survival. Described below and in Table 2 are these effective interventions.
soap, improved water quality, and excreta disposal, respectively [13].
&&
Water provision or use, sanitation, and hygiene A review evaluated the effectiveness of water, sanitation, and hygiene interventions and concluded that water quality interventions (protection or treatment of water at source or point of use) were more effective than interventions to improve water supply (improved source of water and/or improved distribution) [14]. Water quality interventions are associated with a 42% relative reduction in child diarrhea morbidity. Overall sanitation and hygiene interventions lead to an estimated 37 and 31% reduction in child diarrhea morbidity, respectively. A recent review estimated risk reductions for diarrhea of 48, 17, and 36%, with hand washing with
Breastfeeding Initiation of breastfeeding within 1 h of birth, exclusive breastfeeding of infants till 6 months of age, and continued breastfeeding till 2 years of age or longer are recommended [15]. Improved breastfeeding rates are related to reduced diarrhea morbidity and mortality. Breastfeeding initiation within 24 h of birth is associated with a 44–45% reduction in allcause and infection-related neonatal mortality [16], and is thought to mainly operate through the effects of exclusive breastfeeding. Breastfeeding educational and promotional interventions lead to an improvement in exclusive breastfeeding rates (by 43% at 1 day, 30% for 0–1 month, and 90% for 1–6 months age). Correspondingly, rates of ‘not breastfeeding’ also decrease significantly by 32% at 1 day, 30% for 0–1 month, and 18% for 1–6 months [17 ]. Beyond 6 months, educational interventions lead to increase rates of partial breastfeeding by 19%. These findings call for strategies to promote and scale up &
Table 2. Interventions and impacts (with 95% confidence interval) Intervention
Effect estimate
Water, sanitation, and hygiene
48, 17, and 36% risk reductions for diarrhea with hand washing with soap, improved water quality, and excreta disposal, respectively.
Breast feeding education
Educational or counseling interventions increased exclusive breastfeeding rates by 43% (95% CI: 9%-87%) at day 1, by 30% (19–42%) till 1 month, and by 90% (54%, 134%) from 1–6 months. Significant reductions in rates of ‘no breastfeeding’ were also observed; 32% (13%, 46%) at day 1, 30% (20%, 38%) 0–1 month, and 18% (11%, 23%) for 1–6 months.
Preventive zinc supplementation
Diarrhea incidence reduces by 13% (6%, 19%), but no significant impact on mortality.
Vaccines for rotavirus
74% (35–90%) effective against very severe rotavirus infection, 61% (38–75%) against severe rotavirus infection, and hospitalization reduced by 47% (22–64%).
Vaccines for cholera
52% (36%, 65%) effective against cholera infection. Vibriocidal antibodies increased by 124% (32%, 280%).
ORS and RHF
Use of ORS reduced diarrhea-specific mortality by 69% (51–80%) and treatment failure to 0.2% (0.1–0.2%). Limited evidence for the benefit of recommended home fluids.
Dietary management of diarrhea
Lactose-free diets reduce the duration of diarrhea treatment failure significantly by 47% (30%, 60%) and reduce the duration of diarrhea.
Therapeutic zinc supplementation
Reduces all-cause mortality by 46% (12%, 68%) and diarrhea hospitalization by 23% (15%, 31%) but has nonsignificant reduction in diarrhea-specific mortality.
Antibiotics for cholera
63% (29%, 81%) reduction in clinical failure rates and 75% (47%, 88%) reduction in bacteriological failure rates.
Antibiotics for Shigella
Clinical failure rates reduced by 82% (67%, 90%) and bacteriological failure by 96% (88%, 99%).
Antibiotics for cryptosporidiosis
There was a 52% (25%, 70%) reduction in clinical failure rates, and 38% (17%, 54%) reduction in parasitological rates.
Community-based interventions
Community-based interventions are associated with a significant increase in the use of ORS by 160% (60%, 327%) and 80% increase in the use of zinc in diarrhea (67). There was 9% (6%, 11%) increase in care seeking for diarrhea and a 75% (49%, 88%) decline in inappropriate use of antibiotics for diarrhea.
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Global burden of childhood diarrhea and interventions Das et al.
breastfeeding, but there is limited evidence to address the issues of barriers around work environments and supportive strategies such as the provision of maternity leave.
Preventive zinc and vitamin A supplementation About 17.3% of the world’s population is zinc deficient and this is most prevalent in children under 5 years of age in developing countries [18]. Preventive zinc supplementation has no impact on all-cause or diarrhea-specific mortality but leads to a 13% reduction (RR: 0.87; 95% CI: 0.81, 0.94) in the incidence of diarrhea [19]. Vitamin A supplementation is associated with a 28% reduction (RR: 0.72; 95% CI: 0.57, 0.91) in diarrhea-specific mortality and 15% (RR: 0.85; 95% CI: 0.82, 0.87) reduced incidence of diarrhea [20].
Vaccines Rotavirus is the most common cause of severe dehydrating diarrhea in young children globally [5 ]. Newer rotavirus vaccines are associated with reduction in very severe and severe rotavirus infections by 74 (95% CI: 35,90) and 61% (95% CI: 38,75), respectively and rotavirus-related hospitalization among young children by 47% (95% CI: 22, 64), although there are geographic variations observed in vaccine effectiveness [21]. Another important vaccine is for cholera. Although case management with ORS has substantially improved cholera case fatality rates, the disease can still kill rapidly, especially in outbreak settings [22]. Oral cholera vaccine reduces the risk of cholera infection in children under 5 years of age by 52% (RR: 0.48; 95% CI: 0.35, 0.64) [23 ]. This evidence for the effectiveness of oral cholera vaccine makes them a good candidate for the control of cholera in endemic areas and recent research indicates that because of herd protection, even moderate coverage levels of targeted populations with oral vaccine have the potential to lead to almost complete control of cholera [24–26], although this would not prevent outbreaks in other populations. Findings from a recent review on the economic value of diarrheal vaccines suggest that there is an evidence of the economic benefits of rotavirus and cholera vaccines in specific contexts [27]. There are newer vaccines available for Shigella and ETEC although they are not currently recommended. Limited evidence does suggest efficacy of Shigella vaccine against S. flexneri infection at 28% and for S. Sonnei at 53% [23 ]. Despite these initial promising data, there are no vaccines currently available and none &&
&
&
in the pipeline for Shigella and ETEC in the near future.
Therapeutic interventions Interventions for the treatment of diarrhea include ORS, continued feeding, zinc, and antibiotics in some cases. Because the immediate cause of death in most cases of diarrhea is dehydration, the majority of diarrhea deaths can be prevented if dehydration is managed appropriately. ORS and recommended home fluids reduce diarrhea-specific mortality by 69% (95% CI: 51,80%) [28]. Since 2004, zinc is recommended for the treatment of diarrhea and it is associated with a significant reduction in all-cause mortality by 46% (RR 0.54; 95% CI: 0.32, 0.88) and diarrhea-related hospitalizations by 23% (RR: 0.77; 95% CI: 0.69, 0.85) [29]. Current guidelines on the management and treatment of diarrhea in children strongly recommend continued feeding alongside the administration of ORS and zinc therapy. However, there is some debate regarding the optimal diet or dietary ingredients for hastening recovery and maintaining nutritional status in children with diarrhea. An extensive review of feeding strategies and food-based interventions found that the illness duration was shorter and treatment failure risk lower among children with acute diarrheaconsuming lactose-free rather than lactose-containing liquid feeds, no effect of lactose avoidance was shown for stool output or weight gain [30]. It further suggested that locally available ingredients can be used to manage childhood diarrhea as effectively as commercial preparations or specialized ingredients [30]. Antibiotics are also used to treat some forms of bacterial diarrhea especially dysentery. A review [31] evaluated the effectiveness of WHO recommended antibiotics – ciprofloxacin, ceftriaxone, and pivmecillinam for the treatment of dysentery and concluded that antibiotics are effective in reducing the clinical and bacteriological signs and symptoms of dysentery and thus can be expected to decrease diarrhea mortality attributable to dysentery by more than 99%. A review evaluated the effectiveness of antibiotics in diarrhea due to cholera, Shigella, and Cryptosporidium infections [32 ]. The mainstay of therapy in cholera is rehydration, although antibiotics are recommended for severe cases and evidence suggests that antibiotic resulted in a 63% reduction (RR 0.37; 95% CI: 0.19, 0.71) in clinical failure rates whereas bacteriological failure rates were reduced by 75% (RR: 0.25; 95% CI: 0.12, 0.53) [32 ]. Antibiotic management of Shigella results in 82% reduction (RR 0.18; 95% CI: 0.10, 0.33) in clinical failure and a 96% reduction (RR 0.04; 95% CI: 0.01, 0.12) in bacteriological failure
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Gastrointestinal infections &
rates [32 ]. Cryptosporidium may cause life-threatening disease particularly in people who are immunecompromised and contributes significantly to morbidity among children. Evidence shows that antibiotics for the treatment of cryptosporidiosis in immuno-competent patients reduce clinical failure rates by 52% (RR 0.48; 95% CI: 0.30, 0.75), whereas parasitological failure rates are reduced by 38% (RR 0.62; 95% CI: 0.46, 0.83) [32 ]. Other newer and potential interventions to manage diarrhea include probiotics and antiemetics. Probiotics are becoming increasingly popular treatments for diarrhea in some countries. A review undertaken to evaluate the effectiveness of probiotics estimated a 14% reduction in diarrhea duration [33 ]. Despite being a subject of controversy, a number of anti-emetic agents are now commonly administered worldwide in an attempt to reduce vomiting in the proportion of children presenting with acute gastroenteritis and vomiting. A review found that administration of ondansetron reduces the incidence of vomiting and hospitalization by 54% and the requirement for intravenous infusions by 60%. Antiemetics may be of potential benefit in the subset of cases of acute diarrhea with associated severe vomiting precluding oral rehydration. &
&
IMPROVING ACCESS Despite knowing what to do to prevent deaths in children due to diarrhea, we are still lagging behind because most of these interventions have low coverage globally and more in low- and middle-income countries (Fig. 2) [34]. There is little consensus
about the strategies to safeguard delivery of these interventions to reduce disparities and provide equitable access to marginalized populations. Increasing access to high-quality treatment is a priority to reduce deaths. The Integrated Management of Childhood Illnesses [35] approach in health facilities has improved the quality of clinical care. Integrated community case management [36] of pneumonia, diarrhea, and malaria improves access to care, and community health workers can safely and effectively treat diarrhea. Community-based interventions through home visits and community-based sessions for education and promotion of care seeking are effective and cost-effective and can play a major role in improving the coverage of essential interventions. The role of community health workers has been evaluated in various settings in large-scale programs and demonstrated to improve immunization uptake and care seeking for childhood illnesses [37]. A review evaluated the effect of community-based delivery strategies on the coverage and uptake of essential commodities for diarrhea [38 ]. It estimated that these strategies are associated with a 160% (RR: 2.60; 95% CI: 1.59, 4.27) increase in the use of ORS and an 80% increase in the use of zinc in diarrhea [38 ]. There was also a 9% (RR: 1.09; 95% CI: 1.06, 1.11) increase in care seeking and a 75% (RR: 0.25; 95% CI: 0.12, 0.51) decline in the inappropriate use of antibiotics for diarrhea. Financial incentives are also becoming widely used policy strategies to alleviate poverty, promote care seeking, and improve the health of populations. Apart from improving the coverage of the interventions, efforts should also be directed toward improving the quality of clinicbased and community-based care, and new &
&
100.00 90.00
Coverage (%)
80.00 70.00 60.00 50.00 40.00 30.00 20.00 10.00 Use of improved water source
Vitamin A supplementation
Hygienic disposal of children's stools
Improved excreta disposal
ORS
Antibiotics for dysentery
Water connection at home
Hand washing with soap
Exclusive breastfeeding (1-6 month)
Zinc for diarrhrea treatment
Rotavirus vaccine
0.00
FIGURE 2. Coverage of interventions for 75 countdown countries (median with interquartile range). Reproduced from [40 ]. &&
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Global burden of childhood diarrhea and interventions Das et al.
approaches to enhance quality and accessibility of care should continue to be assessed [39].
DISCUSSION The recent Lancet series using the ‘Lives Saved’ tool suggested that if these identified interventions were scaled up to a global coverage to at least 80%, and immunizations to at least 90%; almost all diarrhea deaths could be eliminated [40 ]. Yet, the rate of adoption of these interventions is highly variable and often slow, especially in settings with the greatest need. But global and national attention to childhood diarrhea has been sorely lacking despite the need for it to assume a more prominent position on the child survival agenda given its substantial contribution to child mortality [34], although, recently, there have been efforts to bring it on the radar of national governments and international agencies. The Global Action Plan for Diarrhea and Pneumonia (GAPPD) was launched in April 2013, with an aim to end all preventable deaths, fewer than three deaths per 1000 live births from pneumonia and less than one death per 1000 live births from diarrhea by the year 2025 [41 ]. These targets are plausible especially when we know what works and how. What is required foremost is greater political will and long-term commitment to ensure all children have access to essential treatments such as ORS and zinc for diarrhea, on-time infant vaccination, breastfeeding and high-quality early childhood nutrition with improvement in rates of care-seeking and appropriate case management. In parallel, attention on management, human resources, commodities, programming monitoring and data feedback are required, as well as resources commensurate with the magnitude of the challenge. There is a need to develop clear a country-level strategy and work plan, with key responsibilities assigned. There is also a need for inter-sectoral action transparency and good governance for the effective implementation of the adopted policies. Should we choose to do so, morbidity and mortality due to diarrhea can be alleviated. The role of academia and research cannot be undermined and will continue to play a central role in the development of new vaccines, finding solutions to antibiotic resistance, threats posed by climate change and also to finding ways to improve access to care and improve quality of care and creating demand and supply.
extent. The new integrated GAPPD will guide international efforts to prevent children dying from diarrhea. The efforts will require strong national political backing, the setting of clear priorities, and long-term financial investment. The results we can achieve will repay the effort and beyond. Acknowledgements None.
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CONCLUSION The findings suggest that with proper packaging of interventions and delivery platforms; the burden of childhood diarrhea can be reduced to a greater
Conflicts of interest There are no conflicts of interest.
REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest && of outstanding interest 1. UNICEF: Levels & Trends in Child Mortality, Estimates Developed by the UN Inter-agency Group for Child Mortality Estimation. New York, NY: UNICEF; 2013. Available at http://www.childinfo.org/files/Child_Mortality_Report_ 2013.pdf 2. Liu L, Johnson HL, Cousens S, et al., Child Health Epidemiology Reference Group of WHO and UNICEF. Global, regional, and national causes of child mortality: an updated systematic analysis for 2010 with time trends since 2000. Lancet 2012; 379:2151–2161. 3. Fischer-Walker CL, Perin J, Aryee MJ, et al. Diarrhea incidence in low- and middle-income countries in 1990 and 2010: a systematic review. BMC Public Health 2012; 12:220. 4. Black RE, Victora CG, Walker SP, et al. Maternal and child undernutrition and & overweight in low-income and middle-income countries. Lancet 2013; 382:427–451. A recent study highlighting the current burden, trends, and risk factors of undernutrition globally. 5. Walker CL, Rudan I, Liu L, et al. Global burden of childhood pneumonia and && diarrhoea. Lancet 2013; 381:1405–1416. A thorough review of the current burden, distribution, and risk factors of diarrhea and pneumonia in children globally. 6. Lanata CF, Fischer-Walker CL, Olascoaga AC, et al. Global causes of diarrheal disease mortality in children < 5 years of age: a systematic review. PLoS One 2013; 8:e72788. 7. Kotloff KL, Nataro JP, Blackwelder WC, et al. Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study. Lancet 2013; 382:209–222. 8. Checkley W, Buckley G, Gilman RH, et al. Multicountry analysis of the effects of diarrhoea on childhood stunting. Int J Epidemiol 2008; 37:816–830. 9. Fischer-Walker CL, Lamberti L, Adair L, et al. Does childhood diarrhea influence cognition beyond the diarrhea-stunting pathway. PLoS One 2012; 7:e47908. 10. Rudan I, El Arifeen S, Black RE, Campbell H. Childhood pneumonia and diarrhoea: setting our priorities right. Lancet Infect Dis 2007; 7:56–61. 11. Bhutta ZA, Das JK. Global burden of childhood diarrhea and pneumonia: what can and should be done? Pediatrics 2013; 131:634–636. 12. Lamberti L, Walker CF, Noiman A, et al. Breastfeeding and the risk for diarrhea morbidity and mortality. BMC Public Health 2011; 11 (Suppl 3):S15. 13. Cairncross S, Hunt C, Boisson S, et al. Water, sanitation and hygiene for the prevention of diarrhoea. Int J Epidemiol 2010; 39 (Suppl 1):i193–i205. 14. Waddington H, Snilstveit B, White H, Fewtrell L. Water, sanitation and hygiene interventions to combat childhood diarrhoea in developing countries. International Initiative for Impact Evaluation New Delhi 2009. 15. World Health Organization. The optimal duration of exclusive breastfeeding: report of an expert consultation. Geneva, Switzerland; 28–30 March 2001 Available from: http://www.who.int/nutrition/publications/infantfeeding/WHO_ NHD_01.09/en/index.html. [Accessed 28 March 2014] 16. Debes AK, Kohli A, Walker N, et al. Time to initiation of breastfeeding and neonatal mortality and morbidity: a systematic review. BMC Public Health 2013; 13 (Suppl 3):S19. 17. Haroon S, Das JK, Salam RA, et al. Breastfeeding promotion interventions and & breastfeeding practices: a systematic review. BMC Public Health 2013; 13 (Suppl 3):S20. A thorough review of the strategies which could augment the breastfeeding practices.
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Gastrointestinal infections 18. Das JK, Kumar R, Salam RA, Bhutta ZA. Systematic review of zinc fortification trials. Ann Nutr Metab 2013; 62 (Suppl 1):44–56. 19. Yakoob MY, Theodoratou E, Jabeen A, et al. Preventive zinc supplementation in developing countries: impact on mortality and morbidity due to diarrhea, pneumonia and malaria. BMC Public Health 2011; 11 (Suppl 3):S23. 20. Imdad A, Herzer K, Mayo-Wilson E, et al. Vitamin A supplementation for preventing morbidity and mortality in children from 6 months to 5 years of age. Cochrane Database Syst Rev 2010; Issue 12. Art. No.: CD008524. 21. Munos MK, Walker CLF, Black RE. The effect of rotavirus vaccine on diarrhoea mortality. Int J Epidemiol 2010; 39 (Suppl 1):i56–i62. 22. Piarroux R, Barrais R, Faucher B, et al. Understanding the cholera epidemic, Haiti. Emerg Infect Dis 2011; 17:1161–1168. 23. Das JK, Tripathi A, Ali A, et al. Vaccines for the prevention of diarrhea due & to cholera, Shigella, ETEC and rotavirus. BMC Public Health 2013; 13 (Suppl 3):S11. A timely review for prevention of diarrhea through vaccines – both established vaccines and emerging ones. 24. Ali M, Emch M, von Seidlein L, et al. Herd immunity conferred by killed oral cholera vaccines in Bangladesh: a reanalysis. Lancet 2005; 366:44–49. 25. Longini IM Jr, Nizam A, Ali M, et al. Controlling endemic cholera with oral vaccines. PLoS Med 2007; 4:e336. 26. Luquero FJ, Grout L, Ciglenecki I, et al. Use of vibrio cholerae vaccine in an outbreak in Guinea. N Engl J Med 2014; 370:2111–2120. 27. Rheingans R, Amaya M, Anderson JD, et al. Systematic review of the economic value of diarrheal vaccines. Hum Vaccin Immunother 2014; 10: [Epub ahead of print]. 28. Munos MK, Walker CL, Black RE. The effect of oral rehydration solution and recommended home fluids on diarrhoea mortality. Int J Epidemiol 2010; 39 (Suppl 1):i75–87. 29. Walker CLF, Black RE. Zinc for the treatment of diarrhoea: effect on diarrhoea morbidity, mortality and incidence of future episodes. Int J Epidemiol 2010; 39 (Suppl 1):i63–i69. 30. Gaffey MF, Wazny K, Bassani DG, Bhutta ZA. Dietary management of childhood diarrhea in low- and middle-income countries: a systematic review. BMC Public Health 2013; 13 (Suppl 3):S17. 31. Traa BS, Walker CL, Munos M, Black RE. Antibiotics for the treatment of dysentery in children. Int J Epidemiol 2010; 39 (Suppl 1):i70–i74. 32. Das JK, Ali A, Salam RA, Bhutta ZA. Antibiotics for the treatment of cholera, & Shigella and Cryptosporidium in children. BMC Public Health 2013; 13 (Suppl 3):S10. A current quantitative review for the effect of antibiotics for treatment of three important causes of diarrhea.
458
www.co-infectiousdiseases.com
33. Applegate JA, Walker CLF, Ambikapathi R, Black RE. Systematic review of probiotics for the treatment of community-acquired acute diarrhea in children. BMC Public Health 2013; 13 (Suppl 3):S16. A timely systematic review of an emerging intervention for managing diarrhea. 34. UNICEF 2012. Pneumonia and diarrhoea. Tackling the deadliest diseases for the world’s poorest children. United Nations Children’s Fund. New York Available at http://www.childinfo.org/files/Pneumonia_Diarrhoea_2012.pdf [Accessed March 2014] 35. WHO. Integrated Management of Childhood Illness (IMCI). http://www.who. int/maternal_child_adolescent/topics/child/imci/en/index.html [Accessed 27 March 2014] 36. Young M, Wolfheim C, Marsh DR, Hammamy D. World Health Organization/ United Nations Children’s Fund joint statement on integrated community case management: an equity-focused strategy to improve access to essential treatment services for children. Am J Trop Med Hyg 2012; 87 (Suppl 5): 6–10. 37. Bhutta ZA, Lassi ZS, Pariyo G. Global experience of community health workers for delivery of health related Millennium Development Goals: a systematic review, country case studies, and recommendations for integration into national health systems. Geneva, WHO/Global Health Workforce Alliance 2010. 38. Das JK, Lassi ZS, Salam RA, Bhutta ZA. Effect of community based & interventions on childhood diarrhea and pneumonia: uptake of treatment modalities and impact on mortality. BMC Public Health 2013; 13 (Suppl 3):S29. A systematic review of the community based interventions which could improve the coverage of essential interventions especially in under resourced settings. 39. Gill CJ, Young M, Schroder K, et al. Bottlenecks, barriers, and solutions: results from multicountry consultations focused on reduction of childhood pneumonia and diarrhoea deaths. Lancet 2013; 381:1487–1498. 40. Bhutta ZA, Das JK, Walker N, et al. Interventions to address deaths from && childhood pneumonia and diarrhoea equitably: what works and at what cost? Lancet 2013; 381:1417–1429. A comprehensive review of existing interventions and delivery platforms with the potential impact of scale up in high burden countries. 41. WHO. Ending Preventable Child Deaths from Pneumonia and Diarrhoea by && 2025 The integrated Global Action Plan for Pneumonia and Diarrhoea (GAPPD). World Health Organization/The United Nations Children’s Fund (UNICEF) 2013. http://apps.who.int/iris/bitstream/10665/79200/1/ 9789241505239_eng.pdf. [Accessed 10 March 2014] A global action plan which apart from bringing in the desired attention also gives the direction to tackle childhood diarrhea. &
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