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BMC Public Health. 2012; 12: 276.
Published online Apr 6, 2012. doi:  10.1186/1471-2458-12-276
PMCID: PMC3364857

Systematic review of diarrhea duration and severity in children and adults in low- and middle-income countries

Abstract

Background

Diarrhea is a leading cause of morbidity and mortality globally; yet the overall burden of diarrhea in terms of duration and severity has not been quantified. As improvements in treatment lead to decreases in diarrhea mortality, it is important to understand the substantial impact of diarrhea morbidity on disability among children and adults worldwide.

Methods

We conducted a systematic review to generate estimates of duration and severity outcomes for individuals 0-59 mos, 5-15 yrs, and ≥ 16 yrs, and for 3 severity indexes: mild, moderate, and severe.

Results

We estimate that among children under-five, 64.8% of diarrheal episodes are mild, 34.7% are moderate, and 0.5% are severe. On average, mild episodes last 4.3 days, and severe episodes last 8.4 days and cause dehydration in 84.6% of cases. We estimate that among older children and adults, 95% of episodes are mild; 4.95% are moderate; and 0.05% are severe. Among individuals ≥ 16 yrs, severe episodes typically last 2.6 days and cause dehydration in 92.8% of cases.

Conclusions

Moderate and severe episodes constitute a substantial portion of the total envelope of diarrhea among children under-five (35.2%; about 588 million episodes). Among older children and adults, moderate and severe episodes account for a much smaller proportion of the total envelope of diarrhea (5%), but the absolute number of such episodes is noteworthy (about 21.5 million episodes among individuals ≥ 16 yrs). Hence, the global burden of diarrhea consists of significant morbidity, extending beyond episodes progressing to death.

Background

Diarrhea is a leading cause of morbidity and mortality across all age groups and regions of the world. Among children 0-59 months of age, diarrhea is responsible for 1.236 million deaths annually and is the second leading cause of death in this age group [1]. Though mortality rates among older children, adolescents, and adults are lower than those observed in children under five, diarrhea still poses a substantial burden accounting for approximately 2.8 billion diarrhea episodes among older children, adolescents, and adults [2].

Given the importance of diarrhea as one of the foremost causes of global morbidity and mortality, it is essential to quantify factors, such as duration and severity, critical to quantifying the overall burden of disease attributable to diarrhea. Comprehensive estimates of diarrheal duration and severity will allow for the more accurate assignment of disability adjusted life years (DALYs) in terms of years lost to disability due to diarrheal illness. While various studies conducted throughout the world report on the duration and severity of diarrhea, comprehensive estimates do not exist in the literature. Furthermore, there is a lack of consistency in methods for defining severe, moderate, and mild diarrheal episodes despite the existence of severity scales, such as the Hjelt, Vesikari, and Clark scoring systems, which assign an overall degree of severity based on the sum presentation of symptoms [3-5]. We therefore conducted a systematic literature review with the goal of consolidating available data on the duration and severity of diarrhea and describing the overall burden of episodes among children and adults in low- and middle-income countries.

Methods

Search strategy and selection criteria

We systematically reviewed all literature published from 1990 to 2010 to identify studies reporting measures of diarrhea duration and severity in children and adults. From May 20-27, 2010, we searched in Pubmed using combinations of MeSH search terms: diarrhea, gastroenteritis, duration, persistence, severity, infant, child, teenage, and adult.

We initially screened all unique publications for eligibility based on the relevancy of title and abstract; we then screened the full manuscripts for inclusion and exclusion criteria. We included randomized controlled trials (RCTs), cohort, and observational studies published in any language and conducted in any country. Included studies contained data on diarrhea duration and/or severity in children and/or adults. We excluded studies with unclear methodology and diarrhea recall beyond 2 weeks. We accepted studies defining diarrhea as the passage of ≥ 3 watery stools in a 24-hour period; we also considered mother's report of a change in usual stool consistency or frequency for infants ≤ 11 mo of age, and the diagnosis of diarrhea by a physician or nurse as valid case definitions. We excluded studies describing diarrhea deaths alone since duration and severity outcomes of episodes resulting in death are not generalizable to all diarrhea episodes. We also excluded reports of nosocomial outbreaks, diarrhea due to known chronic or non-infectious illness, and studies that limited inclusion to one etiologic agent. For analytical purposes, we did not include studies that combined outcomes across child/adult age categories or inpatient/outpatient status. Furthermore, for duration outcomes, we included studies on the natural course of diarrhea episodes and excluded those reporting on acute or persistent episodes alone.

Data abstraction

We abstracted measures of diarrhea duration and severity for all ages; for presentation purposes we grouped these data into 3 distinct age categories: 0-59 mos, 5-15 yrs, and ≥ 16 years of age. For studies stratifying outcomes by treatment or HIV-status, we only abstracted data on placebo and HIV-negative individuals, respectively.

We abstracted three outcomes describing diarrhea duration: mean or median duration--reported as the number of days per episode of diarrhea, and the proportion of total diarrheal episodes that became persistent (≥ 14 or ≥ 15 days). If the proportion of persistent cases was skewed due to an intentional sampling bias or matching, we did not include the study for this outcome. To ensure capture of the full length of diarrheal episodes, we also excluded studies solely reporting the duration of diarrheal episodes at baseline.

Multiple outcomes were reported as measures of severity. We abstracted the proportion of individuals suffering from diarrhea with mild, moderate, severe, or any dehydration; vomiting; and bloody stools. We classified necessitating ORS or intravenous fluids as any dehydration. For studies assessing dehydration by both physician perception and WHO classification for dehydration, we utilized the latter. Likewise, if possible, we abstracted outcomes assessed by physicians or trained health workers in place of those estimated by mothers or caregivers. Additional severity outcomes included the mean stool volume (g/kg/day) and mean stool frequency (stools/day). We also abstracted the proportion with low (< 40 g/kg/day), medium (40-70 g/kg/day), and high (> 70 g/kg/day) stool volume. For stool frequency, we abstracted the proportion low (1-5 stools/day), medium (6-9 stools/day), and high (≥ 10 stools/day), as well as the proportion with > 5 stools/day and > 3 stools/day.

We did not find any studies able to quantify the proportion of episodes that remain mild/moderate or that progress to severe. We therefore used care-seeking behavior among caregivers of children < 5 years of age as a proxy for diarrhea severity in this age group. We abstracted care-seeking behavior from the Demographic Health Surveys (DHS) [6]. The DHS reports the number of children ≤ 35 months of age with diarrhea in the two weeks preceding the survey for whom care was sought, as well as the number who were not taken to a health provider.

Data analysis

We used STATA 10.1 to generate combined estimates and 95% confidence intervals for all duration and severity outcomes [7]. To ensure that confidence intervals were lower bound by zero for all outcomes and upper bound by one for proportions, we fit a logistic regression model to data reported as proportions and a Poisson regression model to continuous outcomes. All outcomes were weighted by sample size, which consisted of the total number of episodes. For study designs assessing only one episode per individual, the number of children or adults with diarrhea was considered the total number of episodes. We used the reported diarrheal incidence (number of episodes per child-year) to estimate the sample size for studies evaluating multiple episodes per child without reporting the total number of episodes. We conducted separate analyses for each study type--community, hospital-based inpatient and hospital-based outpatient.

Using the DHS data, we calculated region-specific averages for diarrhea care-seeking. We also calculated the median global estimate of diarrhea care-seeking across regions. The global estimate was used to inform our model describing the total envelope of diarrhea among children under five. Mild cases were defined as those for which no care was sought, and moderate cases were defined as those for which care was sought through a health provider. We assumed that mild and moderate episodes were best described by the duration and severity outcomes derived from community-based studies and hospital outpatient studies, respectively. We used the proportion of outpatient cases presenting with severe dehydration to determine the percentage of moderate cases which progress to severe. Duration and severity outcomes derived from hospital inpatient studies were assumed to best describe severe cases. Table Table11 summarizes the algorithms used to determine the proportion of mild, moderate and severe cases occurring among children 0-59 mos of age; Table Table11 also lists the source of duration and severity outcomes assumed to best describe each diarrhea category.

Table 1
Algorithms used to determine the total envelope of childhood and adult diarrhea

We also designed a model to describe the total envelope of diarrhea among individuals ≥ 16 years of age. We assumed that mild cases were comprised of cases occurring in the community without dehydration, and moderate cases were comprised of the proportion of community cases with any dehydration. In keeping with the assumptions made for the model describing the total envelope of diarrhea among children under-five, we used the proportion of outpatient cases presenting with severe dehydration to determine the percentage of moderate cases progressing to severe. We also assumed that community, hospital outpatient, and hospital inpatient studies best described the duration and severity profiles of mild, moderate, and severe cases, respectively (See Table Table11).

Results

Systematic literature review

The systematic literature search yielded 5708 titles for children (Figure (Figure1),1), of which we identified 41 and 27 studies for inclusion in the analysis of duration [8-48] and severity [8,9,16,19,21,22,25,26,36,39,43,45,49-63], respectively. All included studies reported data on children 0-59 months of age. One duration study also reported outcomes on children 5-15 years of age [24]; no included studies reported data on severity outcomes among older children. Only one study was conducted in a high income country [48]. Of the 8049 titles identified for adults (Figure (Figure1),1), we included four in the duration analysis [24,64-66], and six in the severity analysis [53,64-68]. All but two studies reported data from low- and middle-income countries (LMICs) [65,66]. Across analyses, we included 61 unique studies with study locations spanning across six WHO geographic regions (Figure (Figure22).

Figure 1
Flow chart diagram of the systematic review process. 1Main reasons for exclusion: report of one etiologic agent (n = 30); inadequate definition of diarrhea (n = 15); overlapping age categories (n = 17); no outcome of interest (n = 12); diarrhea recall ...
Figure 2
Location of studies reporting diarrhea duration and severity outcomes for children and adults. Locations of 61 unique studies; one study represented at 3 different locations.

Duration of diarrheal episodes

Among children 0-59 months of age, the weighted mean duration was 4.3 days among cases assessed in the community and 8.4 days among hospital inpatients in LMICs (Table (Table2).2). The mean and median duration reported by the included study conducted in a high-income country were 2.2 days and 1 day, respectively.

Table 2
Estimates of diarrhea duration by age and country income-status

The sole study conducted among children 5-15 years of age reported a mean duration of 2.7 days for episodes assessed in the community (Table (Table2).2). The reported mean duration of episodes among adults ≥ 16 years of age was 3 days in the community and 2.6 days among hospital outpatients in LMICs (Table (Table2);2); in high-income countries, the mean duration of diarrhea was 2.6 days in the community and 4.6 days among outpatients.

Severity of diarrheal illness

Any dehydration was the outcome most frequently cited as a measure of diarrhea severity among children under five. The weighted mean proportion of episodes categorized with any dehydration was 7.3% for episodes assessed in the community, 84.6% among hospital inpatients and 51.4% among hospital outpatients (Table (Table3).3). Any dehydration was also the most frequently reported measure of diarrhea severity among individuals ≥ 16 years of age (Table (Table4).4). The weighted mean proportion of episodes presenting with any dehydration was 92.8% for hospital inpatient studies, 30.1% for hospital outpatient studies, and 5.0% for community studies.

Table 3
Measures of severity of diarrhea among children 0-59 mos of age by study type
Table 4
Measures of severity of diarrhea among individuals ≥ 16 yrs of age by country income-status

Diarrhea care-seeking practices

The DHS-based regional average and global median proportions of care-seeking for diarrhea among children under three years are presented in Table Table5.5. Care-seeking for diarrhea was highest in North Africa/West Asia/Europe (41.0%) and lowest in South/Southeast Asia (31.0%) and West/Middle Africa (26.9%). The median global estimate of care-seeking for diarrhea among children under-five was 35.2%

Table 5
Global care-seeking practices for diarrhea episodes among children ≤ 36 mos of age in low- and middle-income countries

Estimating the total envelope of diarrhea

Figure Figure33 describes the total envelope of diarrhea morbidity among children 0-59 mos of age. Using care-seeking as a proxy for quantifying the proportion of diarrhea episodes which might be considered "mild", we estimate that 64.8% of episodes are mild and the remaining 35.2% of cases are moderate. Of these moderate cases, 1.4% will become severe (i.e. 0.5% of all cases). Using the data from community-based studies we estimate that mild cases last for 4.3 days. We estimate that 15.4% of moderate cases become persistent and 51.4% involve some dehydration. For severe cases, we applied the estimates derived from inpatient studies and thus assumed that severe cases endure 8.4 days with 84.6% resulting in dehydration. Since included outpatient studies did not report mean duration, we estimated the mean duration of moderate cases by averaging that of mild and severe cases; thus, moderate cases last approximately 6.4 days.

Figure 3
Model of the duration and severity of diarrhea among children 0-59 mos of age.

Figure Figure44 describes the total envelope of diarrhea burden among individuals ≥ 16 years of age. Since severe dehydration was not reported by any of the outpatient studies included in this review, we determined the proportion of moderate cases progressing to severe among individuals ≥ 16 years of age by rounding down the proportion derived for children (1.4%); thus, of the 5% of cases characterized as moderate, 1% (i.e. 0.05% of all cases) evolve into severe episodes. Approximately 5% of mild, 30.1% of moderate and 92.8% of severe cases result in dehydration. Although we aimed to characterize the duration of mild, moderate, and severe cases using the averages reported by community, hospital inpatient, and hospital outpatient studies, respectively, mean duration was only reported by one included community study (3.0 days) and one included hospital inpatient study (2.6 days). We therefore averaged the duration reported by the two studies and applied this figure (2.8 days) to the duration of mild, moderate, and severe cases.

Figure 4
Model of the duration and severity of diarrhea among individuals ≥ 16 yrs of age.

Discussion

This systematic review is the first to describe the overall duration and severity of diarrhea among children and adults. To estimate the annual number of diarrhea episodes among children under-five by region, we applied the regional age-adjusted incidences of diarrhea among children 0-59 mos of age to the regional populations of children in that age group. The total number of diarrhea episodes, as well as the breakdown of mild, moderate, and severe episodes in each region, is presented in Table Table6.6. By aggregating the regional numbers, we estimate that among the 1.67 billion diarrhea episodes occurring among children under-five globally per year 1.08 billion (64.8%) are mild; 580 million are moderate (34.7%); and 8 million (0.5%) are severe. By region, the burden of diarrhea is greatest in Africa and Asia; still, Table Table77 illustrates that episodes occurring in Africa tend to be more serious in duration and severity outcomes.

Table 6
Regional breakdown of diarrhea episodes
Table 7
Comparison of outcomes across Africa and Asia

The total envelope of diarrhea cases among individuals ≥ 16 years of age is comprised of approximately 430 million annual episodes of diarrhea [2]. We estimate that approximately 408.5 million episodes are mild (95%); 21.3 million are moderate (4.95%); and 0.2 million are severe (0.05%).

The dearth of studies reporting outcomes for children 5-15 years of age inhibits our ability to directly estimate the burden of diarrhea on this age group. However, a comparison of the mean duration of community-based cases seems to suggest that diarrhea outcomes among children aged 5-15 yrs are more similar to individuals ≥ 16 than to children under-five (Table (Table2).2). Accordingly, we applied the breakdown of mild, moderate, and severe cases estimated for individuals ≥ 16 to the total number of incident cases among children 5-15 years of age. We estimate that of the 200 million diarrheal episodes that occur per year among children 5-15 years of age [2], 190 million are mild (95%); 9.9 million are moderate (4.95%); and 0.1 million are severe (0.05%).

Our review is limited in that we cannot extrapolate our findings onto the duration and severity of diarrhea episodes occurring among HIV-infected individuals. Research comparing diarrhea morbidity and mortality between individuals of discrepant HIV status has shown that HIV increases susceptibility to infectious diseases, including diarrhea. Of the studies we identified, one excluded study observed that in addition to increased diarrhea incidence, HIV-infected children suffered higher duration and a larger proportion of persistent episodes as compared to uninfected children [69]. Moreover, the same study reported increased diarrhea-related mortality among HIV-infected children.

The proportion of moderate/severe episodes among children under-five, which was estimated using the proportion of episodes for which care was sought, is likely underestimated since appropriate care is sought in less than 30-50% of cases in resource poor settings [70]. Given that facility care is under-utilized, moderate/severe episodes among children under-five are also assessed in the community; thus, the duration and severity outcomes derived from community-based studies may not accurately describe mild episodes that do not require facility level care. However, the increasing gravity of duration and severity outcomes across community-based, hospital-inpatient, and hospital-outpatient studies, respectively, suggests that these estimates are plausible and although biased, they represent the best summary of available data.

Conclusions

In this review we classified the total envelope of diarrheal episodes among individuals 0-59 mos, 5-15 years, and ≥ 16 years of age according to diarrhea duration and severity. This information is essential to accurately calculate the age-specific burden of disease and the appropriate allocation of DALYs. Given that the global burden of diarrhea consists of large numbers of episodes beyond those progressing to death, the estimated breakdown of mild, moderate, and severe episodes is increasingly important for informing policy decisions on global health. As programs increasingly scale-up and improve diarrhea treatment, especially among children under-five, estimates of diarrhea morbidity should be used to determine the most effective distribution of funds for interventions focused on diarrhea.

Competing interests

The authors declare that they have no competing interests.

Authors' contributions

LML conducted the systematic review, analysis and led the initial manuscript preparation. CLFW assisted with the analysis and the manuscript preparation. REB provided technical leadership and assisted with the interpretation of the analysis and the final manuscript preparation. All authors read and approved the final manuscript.

Pre-publication history

The pre-publication history for this paper can be accessed here:

http://www.biomedcentral.com/1471-2458/12/276/prepub

Acknowledgements

We would like to thank Jamie Perin for guidance in the statistical analysis. The study was supported by grants from the Bill and Melinda Gates Foundation to the US Fund for UNICEF for CHERG and to the University of Washington for the Global Burden of Disease Project. No funding bodies played any role in the design, writing or decision to publish this manuscript.

References

  • WHO. Causes of death 2008 summary tables. http://www.who.int/entity/gho/mortality_burden_disease/global_burden_disease_DTH6_2008.xls
  • Fischer-Walker CL, Black RE. Diarrhoea morbidity and mortality in older children, adolescents, and adults. Epidemiol Infect. 2010;138(9):1215–1226. doi: 10.1017/S0950268810000592. [PubMed] [Cross Ref]
  • Hjelt K, Grauballe PC, Andersen L, Schiotz PO, Howitz P, Krasilnikoff PA. Antibody response in serum and intestine in children up to six months after a naturally acquired rotavirus gastroenteritis. J Pediatr Gastroenterol Nutr. 1986;5(1):74–80. doi: 10.1097/00005176-198601000-00014. [PubMed] [Cross Ref]
  • Ruuska T, Vesikari T. Rotavirus disease in Finnish children: use of numerical scores for clinical severity of diarrhoeal episodes. Scand J Infect Dis. 1990;22(3):259–267. doi: 10.3109/00365549009027046. [PubMed] [Cross Ref]
  • Clark HF, Borian FE, Bell LM, Modesto K, Gouvea V, Plotkin SA. Protective effect of WC3 vaccine against rotavirus diarrhea in infants during a predominantly serotype 1 rotavirus season. J Infect Dis. 1988;158(3):570–587. doi: 10.1093/infdis/158.3.570. [PubMed] [Cross Ref]
  • ORC Macro, editor. MEASURE DHS. DHS Comparative Reports: Child Morbidity and Treatment Patterns. Calverton, Maryland, USA; 2004.
  • Stata Corp. Statistical Software: Release 10.1. College Station, TX: Stata Corporation; 2008.
  • Ahmed FU, Karim E. Children at risk of developing dehydration from diarrhoea: a case-control study. J Trop Pediatr. 2002;48(5):259–263. doi: 10.1093/tropej/48.5.259. [PubMed] [Cross Ref]
  • Bahl R, Bhandari N, Saksena M, Strand T, Kumar GT, Bhan MK, Sommerfelt H. Efficacy of zinc-fortified oral rehydration solution in 6- to 35-month-old children with acute diarrhea. J Pediatr. 2002;141(5):677–682. doi: 10.1067/mpd.2002.128543. [PubMed] [Cross Ref]
  • Baqui AH, Black RE. El Arifeen S, Yunus M, Chakraborty J, Ahmed S, Vaughan JP: Effect of zinc supplementation started during diarrhoea on morbidity and mortality in Bangladeshi children: community randomised trial. BMJ. 2002;325(7372):1059. doi: 10.1136/bmj.325.7372.1059. [PMC free article] [PubMed] [Cross Ref]
  • Bhandari N, Bhan MK, Sazawal S. Mortality associated with acute watery diarrhea, dysentery and persistent diarrhea in rural north India. Acta Paediatr Suppl. 1992;381:3–6. [PubMed]
  • Biswas R, Biswas AB, Manna B, Bhattacharya SK, Dey R, Sarkar S. Effect of vitamin A supplementation on diarrhoea and acute respiratory tract infection in children. A double blind placebo controlled trial in a Calcutta slum community. Eur J Epidemiol. 1994;10(1):57–61. doi: 10.1007/BF01717453. [PubMed] [Cross Ref]
  • Brunser O, Espinoza J, Araya M, Pacheco I, Cruchet S. Chronic iron intake and diarrhoeal disease in infants. A field study in a less-developed country. Eur J Clin Nutr. 1993;47(5):317–326. [PubMed]
  • Castro MX, Soares AM, Fonseca W, Rey LC, Guerrant RL, Lima AA. Common infectious diseases and skin test anergy in children from an urban slum in northeast Brazil. Braz J Infect Dis. 2003;7(6):387–394. doi: 10.1590/S1413-86702003000600006. [PubMed] [Cross Ref]
  • Checkley W, Gilman RH, Black RE, Lescano AG, Cabrera L, Taylor DN, Moulton LH. Effects of nutritional status on diarrhea in Peruvian children. J Pediatr. 2002;140(2):210–218. doi: 10.1067/mpd.2002.121820. [PubMed] [Cross Ref]
  • Chow CM, Choi K, Nelson EA, Chan PK, Mast TC, DiStefano D, Tam JS, Bresee JS. Use of intravenous fluids in Hong Kong children hospitalised for diarrhoea and relationship to severity and aetiology. Vaccine. 2009;27(Suppl 5):F55–F60. [PubMed]
  • Melo MC, Taddei JA, Diniz-Santos DR, Vieira C, Carneiro NB, Melo RF, Silva LR. Incidence of diarrhea in children living in urban slums in Salvador, Brazil. Braz J Infect Dis. 2008;12(1):89–93. doi: 10.1590/S1413-86702008000100019. [PubMed] [Cross Ref]
  • Dibley MJ, Sadjimin T, Kjolhede CL, Moulton LH. Vitamin A supplementation fails to reduce incidence of acute respiratory illness and diarrhea in preschool-age Indonesian children. J Nutr. 1996;126(2):434–442. [PubMed]
  • Dutta P, Lahiri M, Sen D, Pal SC. Prospective hospital based study on persistent diarrhoea. Gut. 1991;32(7):787–790. doi: 10.1136/gut.32.7.787. [PMC free article] [PubMed] [Cross Ref]
  • Ferreccio C, Prado V, Ojeda A, Cayyazo M, Abrego P, Guers L, Levine MM. Epidemiologic patterns of acute diarrhea and endemic Shigella infections in children in a poor periurban setting in Santiago, Chile. Am J Epidemiol. 1991;134(6):614–627. [PubMed]
  • Fischer Walker CL, Bhutta ZA, Bhandari N, Teka T, Shahid F, Taneja S, Black RE. Zinc supplementation for the treatment of diarrhea in infants in Pakistan, India and Ethiopia. J Pediatr Gastroenterol Nutr. 2006;43(3):357–363. doi: 10.1097/01.mpg.0000232018.40907.00. [PubMed] [Cross Ref]
  • Gupta DN, Sircar BK, Sengupta PG, Ghosh S, Banu MK, Mondal SK, Saha DR, De SP, Sikdar SN, Manna B. et al. Epidemiological and clinical profiles of acute invasive diarrhoea with special reference to mucoid episodes: a rural community-based longitudinal study. Trans R Soc Trop Med Hyg. 1996;90(5):544–547. doi: 10.1016/S0035-9203(96)90315-6. [PubMed] [Cross Ref]
  • Haque R, Mondal D, Kirkpatrick BD, Akther S, Farr BM, Sack RB, Petri WA Jr. Epidemiologic and clinical characteristics of acute diarrhea with emphasis on Entamoeba histolytica infections in preschool children in an urban slum of Dhaka, Bangladesh. Am J Trop Med Hyg. 2003;69(4):398–405. [PubMed]
  • Herbst S, Fayzieva D, Kistemann T. Risk factor analysis of diarrhoeal diseases in the Aral Sea area (Khorezm, Uzbekistan) Int J Environ Health Res. 2008;18(5):305–321. doi: 10.1080/09603120701834507. [PubMed] [Cross Ref]
  • Kolstad PR, Burnham G, Kalter HD, Kenya-Mugisha N, Black RE. The integrated management of childhood illness in western Uganda. Bull World Health Organ. 1997;75(Suppl 1):77–85. [PubMed]
  • Lanata CF, Black RE, Gilman RH, Lazo F, Del Aguila R. Epidemiologic, clinical, and laboratory characteristics of acute vs. persistent diarrhea in periurban Lima, Peru. J Pediatr Gastroenterol Nutr. 1991;12(1):82–88. doi: 10.1097/00005176-199101000-00017. [PubMed] [Cross Ref]
  • Lanata CF, Black RE, Maurtua D, Gil A, Gabilondo A, Yi A, Miranda E, Gilman RH, Leon-Barua R, Sack RB. Etiologic agents in acute vs persistent diarrhea in children under three years of age in peri-urban Lima, Peru. Acta Paediatr Suppl. 1992;381:32–38. [PubMed]
  • Lima AA, Moore SR, Barboza MS Jr, Soares AM, Schleupner MA, Newman RD, Sears CL, Nataro JP, Fedorko DP, Wuhib T. et al. Persistent diarrhea signals a critical period of increased diarrhea burdens and nutritional shortfalls: a prospective cohort study among children in northeastern Brazil. J Infect Dis. 2000;181(5):1643–1651. doi: 10.1086/315423. [PubMed] [Cross Ref]
  • Manun'ebo MN, Haggerty PA, Kalengaie M, Ashworth A, Kirkwood BR. Influence of demographic, socioeconomic and environmental variables on childhood diarrhoea in a rural area of Zaire. J Trop Med Hyg. 1994;97(1):31–38. [PubMed]
  • Mirza NM, Caulfield LE, Black RE, Macharia WM. Risk factors for diarrheal duration. Am J Epidemiol. 1997;146(9):776–785. [PubMed]
  • Mitra AK, Akramuzzaman SM, Fuchs GJ, Rahman MM, Mahalanabis D. Long-term oral supplementation with iron is not harmful for young children in a poor community of Bangladesh. J Nutr. 1997;127(8):1451–1455. [PubMed]
  • Moore SR, Lima AA, Schorling JB, Barboza MS Jr. Soares AM, Guerrant RL: Changes over time in the epidemiology of diarrhea and malnutrition among children in an urban Brazilian shantytown, 1989 to 1996. Int J Infect Dis. 2000;4(4):179–186. doi: 10.1016/S1201-9712(00)90106-1. [PubMed] [Cross Ref]
  • Newman RD, Sears CL, Moore SR, Nataro JP, Wuhib T, Agnew DA, Guerrant RL, Lima AA. Longitudinal study of Cryptosporidium infection in children in northeastern Brazil. J Infect Dis. 1999;180(1):167–175. doi: 10.1086/314820. [PubMed] [Cross Ref]
  • Oberhelman RA, Gilman RH, Sheen P, Taylor DN, Black RE, Cabrera L, Lescano AG, Meza R, Madico G. A placebo-controlled trial of Lactobacillus GG to prevent diarrhea in undernourished Peruvian children. J Pediatr. 1999;134(1):15–20. doi: 10.1016/S0022-3476(99)70366-5. [PubMed] [Cross Ref]
  • Oni GA, Schumann DA, Oke EA. Diarrhoeal disease morbidity, risk factors and treatments in a low socioeconomic area of Ilorin, Kwara State, Nigeria. J Diarrhoeal Dis Res. 1991;9(3):250–257. [PubMed]
  • Pathela P, Zahid Hasan K, Roy E, Huq F, Kasem Siddique A, Bradley Sack R. Diarrheal illness in a cohort of children 0-2 years of age in rural Bangladesh: I. Incidence and risk factors. Acta Paediatr. 2006;95(4):430–437. [PubMed]
  • Rahmathullah L, Underwood BA, Thulasiraj RD, Milton RC. Diarrhea, respiratory infections, and growth are not affected by a weekly low-dose vitamin A supplement: a masked, controlled field trial in children in southern India. Am J Clin Nutr. 1991;54(3):568–577. [PubMed]
  • Ramakrishnan U, Latham MC, Abel R, Frongillo EA Jr. Vitamin A supplementation and morbidity among preschool children in south India. Am J Clin Nutr. 1995;61(6):1295–1303. [PubMed]
  • Sachdev HP, Kumar S, Singh KK, Satyanarayana L, Puri RK. Risk factors for fatal diarrhea in hospitalized children in India. J Pediatr Gastroenterol Nutr. 1991;12(1):76–81. doi: 10.1097/00005176-199101000-00016. [PubMed] [Cross Ref]
  • Sempertegui F, Estrella B, Egas J, Carrion P, Yerovi L, Diaz S, Lascano M, Aranha R, Ortiz W, Zabala A. et al. Risk of diarrheal disease in Ecuadorian day-care centers. Pediatr Infect Dis J. 1995;14(7):606–612. doi: 10.1097/00006454-199507000-00011. [PubMed] [Cross Ref]
  • Strina A, Cairncross S, Prado MS, Teles CA, Barreto ML. Childhood diarrhoea symptoms, management and duration: observations from a longitudinal community study. Trans R Soc Trop Med Hyg. 2005;99(6):407–416. doi: 10.1016/j.trstmh.2004.07.007. [PubMed] [Cross Ref]
  • Sutra S, Srisontrisuk S, Panpurk W, Sutra P, Chirawatkul A, Snongchart N, Kusowon P. The pattern of diarrhea in children in Khon Kaen, northeastern Thailand: I. The incidence and seasonal variation of diarrhea. Southeast Asian J Trop Med Public Health. 1990;21(4):586–593. [PubMed]
  • Teka T, Faruque AS, Fuchs GJ. Risk factors for deaths in under-age-five children attending a diarrhoea treatment centre. Acta Paediatr. 1996;85(9):1070–1075. doi: 10.1111/j.1651-2227.1996.tb14219.x. [PubMed] [Cross Ref]
  • Tielsch JM, Khatry SK, Stoltzfus RJ, Katz J, LeClerq SC, Adhikari R, Mullany LC, Shresta S, Black RE. Effect of routine prophylactic supplementation with iron and folic acid on preschool child mortality in southern Nepal: community-based, cluster-randomised, placebo-controlled trial. Lancet. 2006;367(9505):144–152. doi: 10.1016/S0140-6736(06)67963-4. [PMC free article] [PubMed] [Cross Ref]
  • Valois S, Costa-Ribeiro H Jr. Mattos A, Ribeiro TC, Mendes CM, Lifshitz F: Controlled, double-blind, randomized clinical trial to evaluate the impact of fruit juice consumption on the evolution of infants with acute diarrhea. Nutr J. 2005;4:23. doi: 10.1186/1475-2891-4-23. [PMC free article] [PubMed] [Cross Ref]
  • van der Hoek W, Feenstra SG, Konradsen F. Availability of irrigation water for domestic use in Pakistan: its impact on prevalence of diarrhoea and nutritional status of children. J Health Popul Nutr. 2002;20(1):77–84. [PubMed]
  • Yassin K. Morbidity and risk factors of diarrheal diseases among under-five children in rural Upper Egypt. J Trop Pediatr. 2000;46(5):282–287. doi: 10.1093/tropej/46.5.282. [PubMed] [Cross Ref]
  • Santosham M, Sack RB, Reid R, Black R, Croll J, Yolken R, Aurelian L, Wolff M, Chan E, Garrett S. et al. Diarrhoeal diseases in the White Mountain Apaches: epidemiologic studies. J Diarrhoeal Dis Res. 1995;13(1):18–28. [PubMed]
  • Abu-Elyazeed RR, Wierzba TF, Frenck RW, Putnam SD, Rao MR, Savarino SJ, Kamal KA, Peruski LF Jr, Abd-El Messih IA, El-Alkamy SA. et al. Epidemiology of Shigella-associated diarrhea in rural Egyptian children. Am J Trop Med Hyg. 2004;71(3):367–372. [PubMed]
  • Bahl R, Bhandari N, Hambidge KM, Bhan MK. Plasma zinc as a predictor of diarrheal and respiratory morbidity in children in an urban slum setting. Am J Clin Nutr. 1998;68(2 Suppl):414S–417S. [PubMed]
  • Baqui AH, Zaman K, Persson LA. El Arifeen S, Yunus M, Begum N, Black RE: Simultaneous weekly supplementation of iron and zinc is associated with lower morbidity due to diarrhea and acute lower respiratory infection in Bangladeshi infants. J Nutr. 2003;133(12):4150–4157. [PubMed]
  • Barreto ML, Milroy CA, Strina A, Prado MS, Leite JP, Ramos EA, Ribeiro H, Alcantara-Neves NM, Teixeira Mda G, Rodrigues LC. et al. Community-based monitoring of diarrhea in urban Brazilian children: incidence and associated pathogens. Trans R Soc Trop Med Hyg. 2006;100(3):234–242. doi: 10.1016/j.trstmh.2005.03.010. [PubMed] [Cross Ref]
  • Basak S, Chakraborty PS, Chandy J, Bhattacharya MK, Rasaily R, Ramamurthy T, Sen M. Aetiological studies on hospital inpatients with secretory diarrhoea in Calcutta. J Indian Med Assoc. 1992;90(1):14–15. 16. [PubMed]
  • Daniels DL, Cousens SN, Makoae LN, Feachem RG. A case-control study of the impact of improved sanitation on diarrhoea morbidity in Lesotho. Bull World Health Organ. 1990;68(4):455–463. [PubMed]
  • Hori H, Akpedonu P, Armah G, Aryeetey M, Yartey J, Kamiya H, Sakurai M. Enteric pathogens in severe forms of acute gastroenteritis in Ghanaian children. Acta Paediatr Jpn. 1996;38(6):672–676. doi: 10.1111/j.1442-200X.1996.tb03729.x. [PubMed] [Cross Ref]
  • Lulseged S. Predictors of moderate to severe dehydration in acute diarrhoeal disease: a case-control study. Ethiop Med J. 1992;30(2):69–78. [PubMed]
  • Nguyen TV, Le Van P, Le Huy C, Weintraub A. Diarrhea caused by rotavirus in children less than 5 years of age in Hanoi, Vietnam. J Clin Microbiol. 2004;42(12):5745–5750. doi: 10.1128/JCM.42.12.5745-5750.2004. [PMC free article] [PubMed] [Cross Ref]
  • Patel A, Dibley MJ, Mamtani M, Badhoniya N, Kulkarni H. Zinc and copper supplementation in acute diarrhea in children: a double-blind randomized controlled trial. BMC Med. 2009;7:22. doi: 10.1186/1741-7015-7-22. [PMC free article] [PubMed] [Cross Ref]
  • Penny ME, Peerson JM, Marin RM, Duran A, Lanata CF, Lonnerdal B, Black RE, Brown KH. Randomized, community-based trial of the effect of zinc supplementation, with and without other micronutrients, on the duration of persistent childhood diarrhea in Lima, Peru. J Pediatr. 1999;135(2 Pt 1):208–217. [PubMed]
  • Qazi R, Sultana S, Sundar S, Warraich H. un-Nisa T, Rais A, Zaidi AK: Population-based surveillance for severe rotavirus gastroenteritis in children in Karachi, Pakistan. Vaccine. 2009;27(Suppl 5):F25–F30. [PubMed]
  • Sodemann M, Jakobsen MS, Molbak K, Martins C, Aaby P. Maternal perception of cause, signs and severity of diarrhoea in a suburban west African community. Acta Paediatr. 1996;85(9):1062–1069. doi: 10.1111/j.1651-2227.1996.tb14218.x. [PubMed] [Cross Ref]
  • Aloun DS, Nyambat B, Phetsouvanh R, Douangboupha V, Keonakhone P, Xoumphonhphakdy B, Vongsouvath M, Kirkwood C, Bogdanovic-Sakran N, Kilgore PE. Rotavirus diarrhoea among children aged less than 5 years at Mahosot Hospital, Vientiane, Lao PDR. Vaccine. 2009;27(Suppl 5):F85–F88. [PubMed]
  • Zodpey SP, Deshpande SG, Ughade SN, Hinge AV, Shirikhande SN. Risk factors for development of dehydration in children aged under five who have acute watery diarrhoea: a case-control study. Public Health. 1998;112(4):233–236. [PubMed]
  • Chan SS, Ng KC, Lam PK, Lyon DJ, Cheung WL, Rainer TH. Predictors of positive stool culture in adult patients with acute infectious diarrhea. J Emerg Med. 2002;23(2):125–130. doi: 10.1016/S0736-4679(02)00500-0. [PubMed] [Cross Ref]
  • Dryden MS, Gabb RJ, Wright SK. Empirical treatment of severe acute community-acquired gastroenteritis with ciprofloxacin. Clin Infect Dis. 1996;22(6):1019–1025. doi: 10.1093/clinids/22.6.1019. [PubMed] [Cross Ref]
  • Pereg D, Kimhi O, Tirosh A, Orr N, Kayouf R, Lishner M. The effect of fermented yogurt on the prevention of diarrhea in a healthy adult population. Am J Infect Control. 2005;33(2):122–125. doi: 10.1016/j.ajic.2004.11.001. [PubMed] [Cross Ref]
  • Seas C, Alarcon M, Aragon JC, Beneit S, Quinonez M, Guerra H, Gotuzzo E. Surveillance of bacterial pathogens associated with acute diarrhea in Lima, Peru. Int J Infect Dis. 2000;4(2):96–99. doi: 10.1016/S1201-9712(00)90101-2. [PubMed] [Cross Ref]
  • Weil AA, Khan AI, Chowdhury F, Larocque RC, Faruque AS, Ryan ET, Calderwood SB, Qadri F, Harris JB. Clinical outcomes in household contacts of patients with cholera in Bangladesh. Clin Infect Dis. 2009;49(10):1473–1479. doi: 10.1086/644779. [PMC free article] [PubMed] [Cross Ref]
  • Nte AR, Eneh AU. HIV infection and persistent diarrhoea: a comparative study of HIV positive and HIV negative children. Afr J Med Med Sci. 2008;37(2):149–155. [PubMed]
  • Boschi-Pinto C, Lanata C, RE B. In: Maternal and Child Health: Global Challenges, Problems, and Policies. JE, editor. Washington, D.C.: Springer Publishers; 2009. The global burden of childhood diarrhoea. edn.
  • Fischer Walker CL, Perin J, Aryee M, CB-P, Black RE. Diarrhea incidence in low- and middle-income countries in 1990 and 2010: a systematic review. BMC Public Health. 2012. pp. 12–220. [PMC free article] [PubMed]

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