Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Persistent diarrhea in children in resource-limited countries

Sean R Moore, MD, MS
Section Editor
Deputy Editor
Alison G Hoppin, MD


The great majority of diarrhea episodes last less than one week, however when diarrhea persists for 14 days or longer, it is called persistent diarrhea. In general, infectious disease and pediatric gastroenterology texts use the World Health Organization (WHO) cutoff of ≥2 weeks to delineate persistent from acute episodes [1-3]. Some authors use the term "chronic" for diarrheal illnesses lasting 30 days or longer [3]. Persistent diarrhea may be associated with a chronic enteropathy, with impaired mucosal healing and diminished digestive and absorptive capacity [4], resulting in malabsorption or maldigestion [5]. In resource-limited ("developing") countries, persistent diarrhea is most common in children younger than two years of age, especially in children under one year [6], but can also occur in older children. Although less common than acute diarrhea in resource-limited settings, these prolonged episodes are important not only because of the unpleasantness of having diarrhea but because of their association with overall diarrheal burdens, including malnutrition and increased risk of death [7,8].

The major causes and the prevalence of persistent diarrhea differ between resource-limited and resource-rich countries. In resource-limited settings, persistent diarrhea usually follows an acute episode and typically is associated with serial enteric infections without sufficient time to recover between episodes. Children are at risk of malnutrition and often have other intercurrent illnesses, such as respiratory infections.

In resource-rich countries, children are less likely to be exposed to serial enteric infections and ensuing malnutrition. In these populations, chronic diarrhea is more likely to be caused by underlying disease, such as celiac disease or other autoimmune inflammatory bowel disease. However, enteric infections (particularly in immunocompromised patients), malnutrition, food allergy, and other dietary factors (eg, excessive consumption of juice or withholding feeding during diarrhea and delaying in returning to normal feeding), can play a role in some cases.

The difference in pathophysiology underlying most cases of persistent diarrhea in resource-limited countries as compared with those in resource-rich countries calls for different approaches to diagnosis and management in the two settings.

The pathophysiology and management of persistent diarrhea in resource-limited countries will be reviewed here. Approaches to diagnosis and treatment of diarrheal diseases in resource-rich countries are discussed separately. (See "Approach to the diagnosis of chronic diarrhea in children in resource-rich countries" and "Overview of the causes of chronic diarrhea in children in resource-rich countries".)

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: Oct 24, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Steiner TS, Guerrant RL. Principles and syndromes of enteric infections. In: Principles and practice of infectious diseases, 7th ed, Mandell GL, Bennett JE, Dolin R (Eds), Churchill Livingstone, Philadelphia 2009. Vol 1.
  2. Guarino A, de Marco G. Persistent diarrhea. In: Pediatric gastrointestinal disease, 5th ed, Kleinman RE, Goulet OJ, Mieli-Vergani G (Eds), Decker, Inc, Hamilton, BC 2008. Vol 1.
  3. Shane AL, Mody RK, Crump JA, et al. 2017 Infectious Diseases Society of America Clinical Practice Guidelines for the Diagnosis and Management of Infectious Diarrhea. Clin Infect Dis 2017; 65:e45.
  4. Bhutta ZA, Ghishan F, Lindley K, et al. Persistent and chronic diarrhea and malabsorption: Working Group report of the second World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr 2004; 39 Suppl 2:S711.
  5. Binder HJ. Causes of chronic diarrhea. N Engl J Med 2006; 355:236.
  6. Moore SR, Lima NL, Soares AM, et al. Prolonged episodes of acute diarrhea reduce growth and increase risk of persistent diarrhea in children. Gastroenterology 2010; 139:1156.
  7. Gibbons T, Fuchs GJ. Chronic enteropathy: clinical aspects. Nestle Nutr Workshop Ser Pediatr Program 2007; 59:89.
  8. Mbori-Ngacha DA, Otieno JA, Njeru EK, Onyango FE. Prevalence of persistent diarrhoea in children aged 3-36 months at the Kenyatta National Hospital, Nairobi, Kenya. East Afr Med J 1995; 72:711.
  9. Vanderhoof JA. Chronic diarrhea. Pediatr Rev 1998; 19:418.
  10. Baqui AH, Black RE, Yunus M, et al. Methodological issues in diarrhoeal diseases epidemiology: definition of diarrhoeal episodes. Int J Epidemiol 1991; 20:1057.
  11. Johnston BC, Shamseer L, da Costa BR, et al. Measurement issues in trials of pediatric acute diarrheal diseases: a systematic review. Pediatrics 2010; 126:e222.
  12. Karim AS, Akhter S, Rahman MA, Nazir MF. Risk factors of persistent diarrhea in children below five years of age. Indian J Gastroenterol 2001; 20:59.
  13. Bhandari N, Bhan MK, Sazawal S, et al. Association of antecedent malnutrition with persistent diarrhoea: a case-control study. BMJ 1989; 298:1284.
  14. Manger MS, Taneja S, Strand TA, et al. Poor folate status predicts persistent diarrhea in 6- to 30-month-old north Indian children. J Nutr 2011; 141:2226.
  15. Andrade JA, Fagundes-Neto U. Persistent diarrhea: still an important challenge for the pediatrician. J Pediatr (Rio J) 2011; 87:199.
  16. Mathai J, Raju B, Bavdekar A, Pediatric Gastroenterology Chapter, Indian Academy of Pediatrics. Chronic and persistent diarrhea in infants and young children: status statement. Indian Pediatr 2011; 48:37.
  17. Fine KD, Schiller LR. AGA technical review on the evaluation and management of chronic diarrhea. Gastroenterology 1999; 116:1464.
  18. Das SK, Faruque AS, Chisti MJ, et al. Changing trend of persistent diarrhoea in young children over two decades: observations from a large diarrhoeal disease hospital in Bangladesh. Acta Paediatr 2012; 101:e452.
  19. Fischer Walker CL, Friberg IK, Binkin N, et al. Scaling up diarrhea prevention and treatment interventions: a Lives Saved Tool analysis. PLoS Med 2011; 8:e1000428.
  20. Ochoa TJ, Salazar-Lindo E, Cleary TG. Management of children with infection-associated persistent diarrhea. Semin Pediatr Infect Dis 2004; 15:229.
  21. Black RE. Persistent diarrhea in children of developing countries. Pediatr Infect Dis J 1993; 12:751.
  22. Claeson M, Merson MH. Global progress in the control of diarrheal diseases. Pediatr Infect Dis J 1990; 9:345.
  23. Schiller LR. Chronic diarrhea. Gastroenterology 2004; 127:287.
  24. Islam D, Bandholtz L, Nilsson J, et al. Downregulation of bactericidal peptides in enteric infections: a novel immune escape mechanism with bacterial DNA as a potential regulator. Nat Med 2001; 7:180.
  25. Klish WJ, Udall JN, Rodriguez JT, et al. Intestinal surface area in infants with acquired monosaccharide intolerance. J Pediatr 1978; 92:566.
  26. Klish WJ, Udall JN, Calvin RT, Nichols BL. The effect of intestinal solute load on water secretion in infants with acquired monosaccharide intolerance. Pediatr Res 1980; 14:1343.
  27. Mondal D, Minak J, Alam M, et al. Contribution of enteric infection, altered intestinal barrier function, and maternal malnutrition to infant malnutrition in Bangladesh. Clin Infect Dis 2012; 54:185.
  28. Owino V, Ahmed T, Freemark M, et al. Environmental Enteric Dysfunction and Growth Failure/Stunting in Global Child Health. Pediatrics 2016; 138.
  29. Sullivan PB, Marsh MN. Small intestinal mucosal histology in the syndrome of persistent diarrhoea and malnutrition: a review. Acta Paediatr Suppl 1992; 381:72.
  30. Schneider RE, Viteri FE. Morphological aspects of the duodenojejunal mucosa in protein--calorie malnourished children and during recovery. Am J Clin Nutr 1972; 25:1092.
  31. Penny ME, Paredes P, Brown KH, et al. Lack of a role of the duodenal microflora in pathogenesis of persistent diarrhea and diarrhea-related malabsorption in Peruvian children. Pediatr Infect Dis J 1990; 9:479.
  32. Rana SV, Bhardwaj SB. Small intestinal bacterial overgrowth. Scand J Gastroenterol 2008; 43:1030.
  33. Smith MI, Yatsunenko T, Manary MJ, et al. Gut microbiomes of Malawian twin pairs discordant for kwashiorkor. Science 2013; 339:548.
  34. Abba K, Sinfield R, Hart CA, Garner P. Pathogens associated with persistent diarrhoea in children in low and middle income countries: systematic review. BMC Infect Dis 2009; 9:88.
  35. Ochoa TJ, Barletta F, Contreras C, Mercado E. New insights into the epidemiology of enteropathogenic Escherichia coli infection. Trans R Soc Trop Med Hyg 2008; 102:852.
  36. Becker SL, Vogt J, Knopp S, et al. Persistent digestive disorders in the tropics: causative infectious pathogens and reference diagnostic tests. BMC Infect Dis 2013; 13:37.
  37. Ngan PK, Khanh NG, Tuong CV, et al. Persistent diarrhea in Vietnamese children: a preliminary report. Acta Paediatr 1992; 81 Suppl 381:124.
  38. Fagundes-Neto U, Scaletsky IC. The gut at war: the consequences of enteropathogenic Escherichia coli infection as a factor of diarrhea and malnutrition. Sao Paulo Med J 2000; 118:21.
  39. Ahmed F, Ansaruzzaman M, Haque E, et al. Epidemiology of postshigellosis persistent diarrhea in young children. Pediatr Infect Dis J 2001; 20:525.
  40. Liu J, Platts-Mills JA, Juma J, et al. Use of quantitative molecular diagnostic methods to identify causes of diarrhoea in children: a reanalysis of the GEMS case-control study. Lancet 2016; 388:1291.
  41. Schilling KA, Omore R, Derado G, et al. Factors Associated with the Duration of Moderate-to-Severe Diarrhea among Children in Rural Western Kenya Enrolled in the Global Enteric Multicenter Study, 2008-2012. Am J Trop Med Hyg 2017; 97:248.
  42. Baqui AH, Sack RB, Black RE, et al. Enteropathogens associated with acute and persistent diarrhea in Bangladeshi children less than 5 years of age. J Infect Dis 1992; 166:792.
  43. Lanata CF, Black RE, Maúrtua D, et al. Etiologic agents in acute vs persistent diarrhea in children under three years of age in peri-urban Lima, Perú. Acta Paediatr Suppl 1992; 381:32.
  44. Ramakrishna BS, Venkataraman S, Mukhopadhya A. Tropical malabsorption. Postgrad Med J 2006; 82:779.
  45. Khoshoo V, Bhan MK, Jayashree S, et al. Rotavirus infection and persistent diarrhoea in young children. Lancet 1990; 336:1314.
  46. Shimizu M, Ohta K, Wada H, et al. Cytomegalovirus-associated protracted diarrhoea in an immunocompetent boy. J Paediatr Child Health 2006; 42:259.
  47. Sood M, Booth IW. Is prolonged rotavirus infection a common cause of protracted diarrhoea? Arch Dis Child 1999; 80:309.
  48. Guarino A, Guandalini S, Albano F, et al. Enteral immunoglobulins for treatment of protracted rotaviral diarrhea. Pediatr Infect Dis J 1991; 10:612.
  49. Unicomb LE, Banu NN, Azim T, et al. Astrovirus infection in association with acute, persistent and nosocomial diarrhea in Bangladesh. Pediatr Infect Dis J 1998; 17:611.
  50. Koopmans MP, Goosen ES, Lima AA, et al. Association of torovirus with acute and persistent diarrhea in children. Pediatr Infect Dis J 1997; 16:504.
  51. Feachem RG, Koblinsky MA. Interventions for the control of diarrhoeal diseases among young children: measles immunization. Bull World Health Organ 1983; 61:641.
  52. Amadi B, Kelly P, Mwiya M, et al. Intestinal and systemic infection, HIV, and mortality in Zambian children with persistent diarrhea and malnutrition. J Pediatr Gastroenterol Nutr 2001; 32:550.
  53. Thomas PD, Pollok RC, Gazzard BG. Enteric viral infections as a cause of diarrhoea in the acquired immunodeficiency syndrome. HIV Med 1999; 1:19.
  54. Flores J, Okhuysen PC. Genetics of susceptibility to infection with enteric pathogens. Curr Opin Infect Dis 2009; 22:471.
  55. Cunningham-Rundles S, McNeeley DF, Moon A. Mechanisms of nutrient modulation of the immune response. J Allergy Clin Immunol 2005; 115:1119.
  56. Usha N, Sankaranarayanan A, Walia BN, Ganguly NK. Assessment of preclinical vitamin A deficiency in children with persistent diarrhea. J Pediatr Gastroenterol Nutr 1991; 13:168.
  57. Bhan MK, Bhandari N. The role of zinc and vitamin A in persistent diarrhea among infants and young children. J Pediatr Gastroenterol Nutr 1998; 26:446.
  58. Rahman MM, Vermund SH, Wahed MA, et al. Simultaneous zinc and vitamin A supplementation in Bangladeshi children: randomised double blind controlled trial. BMJ 2001; 323:314.
  59. Lazzerini M, Ronfani L. Oral zinc for treating diarrhoea in children. Cochrane Database Syst Rev 2012; :CD005436.
  60. WHO/CAH Diarrhoea treatment guidelines including new recommendations for the use of ORS and zinc supplementation for clinic-based healthcare workers. UNICEF, MOST, USAID, Geneva, 2005. Available at: www.mostproject.org (Accessed on January 08, 2008).
  61. Bhutta ZA, Bird SM, Black RE, et al. Therapeutic effects of oral zinc in acute and persistent diarrhea in children in developing countries: pooled analysis of randomized controlled trials. Am J Clin Nutr 2000; 72:1516.
  62. Lukacik M, Thomas RL, Aranda JV. A meta-analysis of the effects of oral zinc in the treatment of acute and persistent diarrhea. Pediatrics 2008; 121:326.
  63. Feachem RG, Koblinsky MA. Interventions for the control of diarrhoeal diseases among young children: promotion of breast-feeding. Bull World Health Organ 1984; 62:271.
  64. Sazawal S, Bhan MK, Bhandari N. Type of milk feeding during acute diarrhoea and the risk of persistent diarrhoea: a case control study. Acta Paediatr Suppl 1992; 381:93.
  65. Tovo PA, de Martino M, Gabiano C, et al. Prognostic factors and survival in children with perinatal HIV-1 infection. The Italian Register for HIV Infections in Children. Lancet 1992; 339:1249.
  66. Guarino A, Tarallo L, Guandalini S, et al. Impaired intestinal function in symptomatic HIV infection. J Pediatr Gastroenterol Nutr 1991; 12:453.
  67. Castaldo A, Tarallo L, Palomba E, et al. Iron deficiency and intestinal malabsorption in HIV disease. J Pediatr Gastroenterol Nutr 1996; 22:359.
  68. Canani RB, Cirillo P, Mallardo G, et al. Effects of HIV-1 Tat protein on ion secretion and on cell proliferation in human intestinal epithelial cells. Gastroenterology 2003; 124:368.
  69. Feasey NA, Healey P, Gordon MA. Review article: the aetiology, investigation and management of diarrhoea in the HIV-positive patient. Aliment Pharmacol Ther 2011; 34:587.
  70. Dutta P, Mitra U, Dutta S, et al. Hypo-osmolar oral rehydration salts solution in dehydrating persistent diarrhoea in children: double-blind, randomized, controlled clinical trial. Acta Paediatr 2000; 89:411.
  71. Huilan S, Zhen LG, Mathan MM, et al. Etiology of acute diarrhoea among children in developing countries: a multicentre study in five countries. Bull World Health Organ 1991; 69:549.
  72. World Health Organization. The treatment of diarrhoea, a manual for physicians and other senior health workers. WHO/FCH/CAH/03.7. Geneva: World Health Organization, 2005. Available at: http://www.who.int/child_adolescent_health/documents/9241593180/en/index.html (Accessed on November 18, 2009).
  73. Guarino A, Albano F, Working Group on Intestinal Infections of the Italian Society of Paediatric Gastroenterology and Hepatology. Guidelines for the approach to outpatient children with acute diarrhoea. Acta Paediatr 2001; 90:1087.
  74. World Health Organization. Expert Consultation on Oral Rehydration Salts (ORS) Formulation. WHO/FCH/CAH/01.22 (updated 4/2014). Available at: http://rehydrate.org/ors/expert-consultation.html (Accessed on May 25, 2016).
  75. Evaluation of an algorithm for the treatment of persistent diarrhoea: a multicentre study. International Working Group on Persistent Diarrhoea. Bull World Health Organ 1996; 74:479.
  76. de Mattos AP, Ribeiro TC, Mendes PS, et al. Comparison of yogurt, soybean, casein, and amino acid-based diets in children with persistent diarrhea. Nutr Res 2009; 29:462.
  77. Bhan MK, Bhandari N, Bahl R. Management of the severely malnourished child: perspective from developing countries. BMJ 2003; 326:146.
  78. WHO/UNICEF Joint statement: Clinical management of acute diarrhea. WHO/FCH/CAH/04.7. Geneva, 2004. Available at: http://www.emro.who.int/cah/pdf/who_unicef_statement.pdf (Accessed on October 19, 2010).
  79. Bhutta ZA, Black RE, Brown KH, et al. Prevention of diarrhea and pneumonia by zinc supplementation in children in developing countries: pooled analysis of randomized controlled trials. Zinc Investigators' Collaborative Group. J Pediatr 1999; 135:689.
  80. Farthing MJ. Diarrhoea: a significant worldwide problem. Int J Antimicrob Agents 2000; 14:65.
  81. World Health Organization. The management of bloody diarrhea in young children. WHO/CDD/94.49. Geneva: World Health Organization, 1994.
  82. Traa BS, Walker CL, Munos M, Black RE. Antibiotics for the treatment of dysentery in children. Int J Epidemiol 2010; 39 Suppl 1:i70.
  83. Ahmed FU, Karim E. Children at risk of developing dehydration from diarrhoea: a case-control study. J Trop Pediatr 2002; 48:259.
  84. Bhatnagar S, Bhan MK, Singh KD, Shrivastav R. Prognostic factors in hospitalized children with persistent diarrhea: implications for diet therapy. J Pediatr Gastroenterol Nutr 1996; 23:151.
  85. Bernaola Aponte G, Bada Mancilla CA, Carreazo NY, Rojas Galarza RA. Probiotics for treating persistent diarrhoea in children. Cochrane Database Syst Rev 2013; :CD007401.
  86. Grenov B, Namusoke H, Lanyero B, et al. Effect of Probiotics on Diarrhea in Children With Severe Acute Malnutrition: A Randomized Controlled Study in Uganda. J Pediatr Gastroenterol Nutr 2017; 64:396.