Risk factors for persistent diarrhea

It is important to recognize the major risk factors for development of persistent diarrhea, as appropriate case management of acute diarrhea is key to the prevention of prolonged episodes.

Specific pathogens

The association of specific bacterial and viral infections with persistent diarrhea has been the subject of considerable debate.30,31 Evidence from

Risk factors for persistent diarrhea 195

Figure 12.2 Mechanisms and effects of enteropathy of malnutrition and prolonged diarrhea.

Risk Factors For Acute Diarrhea

Figure 12.2 Mechanisms and effects of enteropathy of malnutrition and prolonged diarrhea.

Bangladesh suggests that recurrent bouts of infection with pathogens such as Shigella lead to prolongation of the duration of successive diar-rheal episodes. Although several studies have identified an association between persistent diarrhea and enteroaggregative Escherichia coli in the small bowel, this is by no means pathognomonic,32 nor is there a particular pattern of small-bowel microbial colonization or overgrowth seen in most cases. In parts of Africa endemic for HIV an association of persistent diarrhea with cryptosporidio-sis and other pathogens19-21,33 is well recognized, but may represent a manifestation of immunodeficiency.


Persistent diarrhea is commonly seen in association with significant malnutrition, and the relationship may be bi-directional. It is widely recognized that diarrheal episodes, especially if invasive, may become prolonged in malnourished children. The recent evidence of micronutrient deficiencies, especially of zinc and vitamin A in malnourished children with persistent diarrhea, indicates impaired immunological mechanisms for clearing infections as well as ineffective mucosal repair mechanisms. From initial studies indicating the potential benefit of zinc supplementation on reducing the risk of prolonged diarrhea,34 the evidence of the benefit of zinc supplements in children with persistent diarrhea was equivocal.35,36 However, a recent meta-analysis of zinc supplementation in diarrheal illnesses indicated a significant reduction in duration and severity of diarrheal illnesses.37 Thus, zinc deficiency may significantly contribute to the prolongation of mucosal injury and delayed intestinal repair mechanisms.

Dietary risk factors

While many children with persistent diarrhea are lactose-intolerant, the role of specific dietary allergies in inducing and perpetuating enteropathy of malnutrition is unclear. Several studies have highlighted the high risk of prolonged diarrhea with lactation failure and early introduction of artificial feeds in developing countries. In particular, the administration of unmodified cow's or buffalo's milk is associated with prolongation of diarrhea, suggesting the potential underlying role of milk protein enteropathy.26,38

Inappropriate management of acute diarrhea

The association of prolongation of diarrhea with starvation and inappropriately prolonged administration of parenteral fluids has been recognized for over half a century. Continued breast feeding is important; unnecessary food withdrawal, and replacement of luminal nutrients, especially breast milk, with non-nutritive agents is a major factor in prolonging mucosal injury after diarrhea. In particular, blanket administration of antibiotics and anti-motility agents and semi-starvation diets should be avoided in cases of prolonged diarrhea.39,40 While parenteral nutrition has been occasionally life saving in selected cases in developing countries,41 it is clearly an impractical option for most of the developing world. There is now clear evidence supporting the enteral route for nutritional rehabilitation of malnourished children with persistent diarrhea.12 Starvation has been shown to have deleterious effects on the intestinal mucosa,42 with a reduction in the nutritive transporters for glutamine and arginine.43 It is therefore imperative that malnourished children with persistent diarrhea should receive enteral nutrition during their period of rehabilitation.

The aforementioned risk factors highlight the importance of recognizing that optimal management of diarrheal episodes is key to the prevention of persistent diarrhea. It is thus necessary that, given the close relationship between diarrheal disorders and malnutrition, persistent diarrhea be widely recognized as a nutritional disorder,44,45 and optimal nutritional rehabilitation be considered as the cornerstone of its management.12

the chronicity of the disorder, prolonged hospitalization may be problematic in developing countries and, whenever possible, ambulatory or home-based therapy must be supported.

The following represent the basic principles of management of persistent diarrhea. A suggested therapeutic approach is indicated in Figure 12.3.

Rapid resuscitation, antibiotic therapy and stabilization

Most children with persistent diarrhea and associated malnutrition are not severely dehydrated, and oral rehydration may be adequate. However, acute exacerbations and associated vomiting may require brief periods of intravenous rehydration with Ringer's lactate. Acute electrolyte imbalance such as hypokalemia and severe acidosis may require correction. More importantly, associated systemic infections (bacteremia, pneumonia and urinary tract infection) are well recognized in severely malnourished children with persistent diarrhea and a frequent cause of early mortality. Children must be screened for these at admission. Almost 30-50% of malnourished children with persistent diarrhea may have an associated systemic infection requiring resuscitation and antimicrobial therapy.46,47 In severely ill children requiring hospitalization, it may be best to cover with parenteral antibiotics at admission (usually ampicillin and gentamicin) while awaiting the results of cultures. It should be emphasized that there is little role for oral antibiotics in persistent diarrhea, as in most cases the original bacterial infection triggering the prolonged diarrhea has disappeared by the time the child presents. One possible exception may be adjunctive therapy for cryptosporidiosis in children with HIV and persistent diarrhea.48

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