Persistent diarrhea (PD) is an episode of diarrhea of presumed infectious etiology, which starts acutely but lasts for more than 14 days, and excludes chronic or recurrent diarrheal disorders such as tropical sprue, gluten sensitive enteropathy or other hereditary disorders [1].

WHO estimates that while persistent diarrhea accounts for only 10 percent of diarrheal episodes, as much as 35 percent of deaths from diarrhea in children under 5 years of age occur from it. Community studies show that for every 100 children below 4 years, seven cases of persistent diarrhea occur every year [2] and that it is responsible for one-third to half of all diarrhea related mortality [3-5]. Twenty per cent of acute diarrheal episodes in malnourished children persist beyond two weeks. Sixty per cent of PD occurs before 6 months and 90% below 1 year of age [6].

The pathogenesis though not well understood, is believed to be multifactorial - persistent mucosal injury due to specific pathogens (E. coli, Shigella, Salmonella, Campylobacter), sequential infections with multiple pathogens, and host factors (macro, micronutrient deficiency and compromised immune system). In a recent study, 23% of children with shigellosis developed persistent diarrhea [7]. The risk of an acute diarrhea becoming persistent is many fold more in malnourished children and in those with secondary carbohydrate malabsorption [8]. Other risk factors include very young age, previous infections, recent introduction of animal milk, irrational usage of antibiotics, and lack of breast feeding [1]. In persistent diarrhea, chronic inflammation and defective intestinal repair result in abnormal mucosal morphology, leading to poor absorption of luminal nutrients and increased permeability of the bowel to abnormal dietary or microbial antigens [9]. The severity of these changes is greater in younger children due to delayed intestinal mucosal maturation.

Micronutrient deficiencies contribute to poor intestinal repair and zinc deficiency may result in prolongation of mucosal injury and delayed intestinal repair mechanisms [10]. The role of immune deficiency in persistent diarrhea is not well understood [11]. Micronutrient deficiency itself may cause transient immune deficiency which could be an important risk factor for persistent diarrhea [12]. Persistent diarrhea is being increasingly recognized as a manifestation of HIV infection and crypto-sporidiosis [13,14].

Intestinal mucosal damage and consequent problems with nutrient absorption are common features in all children with persistent diarrhea and therefore nutritional management is the cornerstone of treatment [15-17]. Since persistent diarrhea often requires management in community settings, diets which are inexpensive are currently being used. Milk cereal mixes containing modest amount of milk are as efficacious as milk free diet in the early stages, when diarrhea is not severe. Milk free diet with simple or complex carbohydrates is ideal for those with severe disease. Monosaccharide based diet is required only for those who do not respond to these measures. In a multi-centric study involving 560 children aged 4-36 months; the overall success rate with this regimen was 80% [18].

At admission, most patients have dehydration and electrolyte imbalance which will need correction. Evidence suggests that low osmolality ORS is efficacious in management of dehydration in persistent diarrhea [19,20].

The energy density of the feeds should be around 1 Cal/g and an intake of about 100 Cals/kg bodyweight should be aimed at. Micronutrients should be given for at least 2 wk; multivitamin (twice the RDA), folic acid (5 mg day 1, then 1 mg/day), zinc (2 mg/kg/day) and copper (0.3 mg/kg/day). Oral vitamin A (<6 months 50,000 IU, 6-12 months 100,000 IU) and a dose of parenteral Vitamin K should be given at admission. Severely malnourished infants require 50% magnesium sulphate 0.2 mL/kg/dose twice daily for 2 -3 days. After the infant has begun to improve and is gaining weight, 3 mg/kg/day of iron is added. Analysis of four large studies reported a beneficial effect of zinc in infants with persistent diarrhea [21].

Available evidence does not support the routine use of antibiotics directed against enteric pathogens. Published data is presently insufficient to recommend the use of probiotics. There is no role for racecadotril or steroids. Unusual enteropathogens, sucrase/isomaltase deficiency, severe glucose malabsorption, and severe systemic infection are reasons for failure to respond [22].

Infants less than six months of age continue to remain an area of concern, since most of the foods recommended cannot be used in them. They need extensively hydrolyzed 100% bovine casein infant formulas and elemental amino acid formulas which are currently not available in India. Another major problem is the inability to manage unresponsive children in most health care settings. Regional centers equipped to manage them are urgently needed. Current nutritional management requires prolonged hospital stay and facilities to prepare special diets, which is a problem for many health-care settings. Diet regimens in general have poor acceptability among parents of the upper strata of society. Parent education and uniform protocols of management to be followed by all pediatricians in India may be a possible solution.

Improvements in nutritional status of infants and children as well as prevention and rational management of acute diarrhea are keys to prevention of PD. Cost effective interventions in the community include promotion of exclusive breastfeeding, safe complementary feeding practices, promotion of safe drinking water, low osmolality ORS, zinc supplementation, avoiding unnecessary antibiotics and continued feeding during diarrhea [23].

Diarrhea which lasts for more than 14 days, is usually non infectious and associated with malabsorption is labeled as chronic diarrhea.

The true incidence of chronic diarrhea in India is not known. There are many causes for chronic diarrhea and with better facilities these are being increasingly diagnosed in India [6,24]. In a study on 137 children with chronic diarrhea, celiac disease was documented in 26%, parasitic infections in 9% and tuberculosis in 5% of children [25].

Infants with chronic diarrhea require a two stage evaluation. The first involves assessing the type of diarrhea, and the second to determine the specific etiology. Table I illustrates the basic tests required for the first stage and the current scenario in India.

Table I



Basic Tests in the Diagnosis of Chronic Diarrhea

There is limited capability of most settings to investigate children with chronic diarrhea primarily due to the poor availability of diagnostic tests in India. Some of the more common causes and the basis of their diagnosis in India are:

CMPA, celiac disease, giardiasis and lactose intolerance are easily treatable. CMPA is now being increasingly recognized in India [27]. These children need extensively hydrolyzed 100% bovine casein infant formulas or elemental amino acid formulae that are currently not available in India. Soy formulations are not recommended, particularly in those below 6 months of age. Gluten free diet for celiac disease is successfully being practiced in many centers, but the food industry needs to be sensitized to this disease. Patient support groups are currently being formed in some cities. Lactose free formula for secondary lactose intolerance is freely available, but they are probably being over-used. Elemental formulae are essential in the management of intractable diarrhea of infancy. Response to steroids or immuno-suppression confirms autoimmune enteropathies. Small intestinal transplantation is currently not available in India.

Parenteral nutrition has a major role to play in management of chronic diarrhea. However it involves considerable cost, expertise and infrastructure and cannot therefore be suggested as a viable treatment option

There is very little awareness about CMPA, Celiac disease and immunodeficiency associated diarrhea among pediatricians. The practice of giving a trial of gluten free diet without duodenal biopsy and serological tests is becoming widespread. Creating awareness among primary care physicians is the only solution for these problems. The lack of availability of many specific diagnostic tests and their prohibitive cost in most parts of the country is also a problem. Regional laboratories need to be urgently established to overcome this limitation.

Writing Committee: John Matthai (Coimbatore), Bhaskar Raju (Chennai), and Ashish Bavdekar(Pune).

Funding: None.

Competing interests: None stated.

1. Memorandum from a WHO meeting. Persistent diarrhea in children in developing countries. Bull WHO. 1988;66:709-17.

2. Bhan M K, Bhandari N, Sazawal S, Clemens J, Raj P, Levine MM, et al. Longitudinal study of diarrhoeal disease among young children in rural north India. Bull WHO. 1989;67:281-8.

3. Schorling JB, Wanke CA, Schorlling SK, McAullife JF, de Souza MA, Guerrat RL. A prospective study of persistent diarrhea among children in an urban Brazilian slum: patterns of occurrence and etiologic agents. Am J Epidemiol. 1990;132:144–56.

4. Fauveau V, Henry FJ, Briend A, Yunus M, Chakraborty J. Persistent diarrhea as a cause of childhood mortality in rural Bangladesh. Acta Paediatr Suppl. 1992;381:12–4.

5. Alam S, Admed SH, Lamba LMS. Clinical profile of persistent diarrhea in a DTTU. Indian Pediatr. 1997;34:631-5.

6. Mittal SK. Chronic Diarrhea in tropics. Indian J Pediatr. 1999;66:S4-S15.

7. Ahmed F, Ansaruzzaman M, Haque E, Rao MR, Clemens JD. Epidemiology of post shigellosis persistent diarrhea in young children. Pediatr Infect Dis J. 2001;20:525-30.

8. Fauveau V, Henry FJ, Briend A, Yunus M, Chakraborty J. Persistent diarrhea as a cause of childhood mortality in rural Bangladesh. Acta Paediatr. 1992;381:S 12–4.

9. Sullivan PB. Studies of the small intestine in persistent diarrhea and malnutrition: the Gambian experience. J Pediatr Gastroenterol Nutr. 2002;34:S11-3.

10. Sazawal S, Black RE, Bhan MK, Bhandari N, Sinha A, Jalla S. Zinc supplementation in young children with acute diarrhea in India. N Engl J Med. 1995;333:839-44.

11. Baqui AH, Black RE, Sack RB, Chowdhury HR, Yunus M, Siddique AK. Malnutrition, cell-mediated immune deficiency and diarrhea: a community-based longitudinal study in rural Bangladeshi children. Am J Epidemiol. 1993;137:355-65.

12. Taniguchi K, Rikimaru T, Yartey JE, Akpedonu, P, Armar-Klemesu MA, Nkrumah FK, et al. Immunological background in children with persistent diarrhea in Ghana. Pediatr Int. 1999;4:162-7.

13. Adejuyigbe EA, Oyelami O, Onayemi O, Durosinmi MA. Paediatric HIV/AIDS in Ile-Ife, Nigeria. Cent Afr J Med. 2003;49:74-8.

14. Amadi B, Kelly P, Mwiya M, Mulwazi E, Sianongo S, Changwe F, et al. Intestinal and systemic infection, HIV, and mortality in Zambian children with persistent diarrhea and malnutrition. J Pediatr Gastroenterol Nutr. 2001;32:550-4.

15. Bhutta ZA, Hendricks KH. Nutritional management of persistent diarrhea in childhood: a perspective from the developing world. J Pediatr Gastroenterol Nutr. 1996;22:17-37.

16. Bhan MK, Bhandari N, Bhatnagar S, Bahl R. Epidemiology and management of persistent diarrhoea in children of developing countries. Indian J Med Res. 1996;104:103-14.

17. International Working Group on Persistent Diarrhoea. Evaluation of an algorithm for the treatment of persistent diarrhoea: a multicentre study. Bull World Health Organ. 1996;74:479-89.

18. Bhandari N, Bahl R, Saxena M, Taneja S, Bhan MK. Prognostic factors for persistent diarrhea managed in a community setting. Indian J Pediatr. 2000;67: 739-45.

19. Sarker SA, Mahalanabis D, Alam NH, Sharmin S, Khan AM, Fuchs GJ. Reduced osmolarity oral rehydration solution for persistent diarrhea in infants: a randomized controlled clinical trial. J Pediatr. 2001;138:532-8.

20. Dutta P, Mitra U, Dutta S, Manna B, Chatterjee MK, De A, et al. Hypo-osmolar oral rehydration salts solution in dehydrating persistent diarrhoea in children: double-blind, randomized, controlled clinical trial. Acta Paediatr. 2000;89:411-6.

21. Bhutta ZA, Bird SM, Black RE, Brown KH, Gardner JM, Hidayat A, 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;72:1516-22.

22. Bhatanagar S, Bhan MK, Singh KD, Srivastav R. Prognostic factors in hospitalized children with persistent diarrhea: Implications for diet therapy. J Pediatr Gastroenterol Nutr. 1996;23:151-8.

23. Sheth M, Obrah M. Diarrhea prevention through food safety education. Indian J Pediatr. 2004;71:879-82.

24. Ganesh R, Suresh N, Sathiasekharan M. Celiac disease, still an uncommon problem in Tamilians? Indian J Gastroenterol. 2009;28:189.

25. Yachha SK, Misra S, Malik A K, Nagi B, Mehta S. Spectrum of malabsorption in North Indian children. Indian J Gastroenterol. 1993;12:120-5.

26. Yachha SK, Poddar U. Celiac disease in India. Indian J Gastroenterol. 2007;26:230-7.