In about 5% of acute diarrhea cases in the community, illness may last for more than 2 weeks or 3 weeks, because of persistent colonization of upper small intestines by microbes, dietary allergies (especially in very young infants), and carbohydrate intolerance (because of intestinal damage resulting in low levels of disaccharidases).
Infants and children with decreased host immunity, such as after an attack of measles, or delayed repair of intestinal damage because of associated protein–energy malnutrition (PEM) are more prone to protracted diarrhea. Younger infants who are weaned very early develop intolerance to food proteins such as cow’s milk or even soya milk. Poor personal hygiene and environmental or food contamination may lead to recurrent intestinal infections before the infant recovers from a previous episode. Protozoal infections with Giardia lamblia or Entamoeba histolytica and inadequate treatment of acute diarrhea are other important causes.
Epidemiologically, around 10% of all acute diarrheal episodes tend to persist beyond 14 days. However, majority of these episodes represent only a normal variation in natural history of different etiological agents. A study has shown that 10% of even rotavirus diarrhea may last for as long as 21 days but may have no other clinical problems. The frequency and consistency of stools following
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Shigella infection very often last for several days following acute illness. Hence, mere prolongation of diarrheal episode should not become a cause of worry. Attempt should be made to focus on those episodes, which are associated with weight loss, as these are the cases, which are likely to have a bad outcome.
In these children, attention should be focused on adequate nutrition intake and selective judicious use of antimicrobials. Low lactose diets may help when there is carbohydrate intolerance. If the child is given half-diluted milk for a few days with a phased increase in the concentration of milk given in the next week, most cases of protracted diarrhea improve. Prevention and management of protracted diarrhea primarily involves encouragement of breastfeeding and good nutritional management of acute diarrhea.
PERSISTENT DIARRHEA
This has been defined by World Health Organization (WHO) as a diarrhea starting acutely and lasting for more than 14 days. This is seen largely in infants, with more than 60% of episodes occurring within 6 months of age and 90% before 1 year of age. About 10% of acute diarrheal episodes tend to become persistent. The term “protracted”
means a drawn out prolongation of illness. However, for practical purposes, persistent diarrhea episodes, which are associated with failure to thrive, have been labeled as protracted diarrhea. About 10% of persistent diarrhea cases develop the problem of weight loss or inadequate weight gain.
The exact cause of persistent/protracted diarrhea is not known.
A variety of risk factors have been thought of. These include malnutrition, younger age group, impaired cell-mediated immunity, recent introduction of animal milk, enteroadherent Escherichia coli, enteropathogenic E. coli (EPEC), Shigella and inappropriate use of
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antibiotics. It is also thought that the early introduction of top milk introduces them to pathogenic bacteria as well as foreign protein, which causes occurrence of recurrent gut infection and sensitization of the infants to the foreign proteins. Malnutrition leads to delay in replenishment of damaged gut mucosa causing an increased duration of diarrhea.
Apart from the possible role of enteropathogens, a large number of specific conditions may be responsible for causation of persistent diarrhea. Majority of these cases have some underlying factors:
systemic infections, persistent gut infection, lactose intolerance, cow’s milk protein intolerance (CMPI), mucosal damage, malnutrition (PEM/vitamin A/zinc deficiency), and colitis/antibiotic colitis.
Systemic infection: These infections tend to be recurring and children need to be carefully screened to detect and manage these infections. This means complete blood count, urine examination and culture, X-ray of chest, Mantoux, and blood culture. In areas where human immunodeficiency virus (HIV) is highly prevalent, relevant investigations should be carried out.
Persistent gut infection: Salmonella typhimurium is an important enteropathogen in persistent diarrhea. Enteroadhesive and entero- aggregative Escherichia coli are the two other important causes.
Lactose intolerance: It is due to lactase enzyme which is present in the most superficial layers of jejunal mucosa and hence most vulnerable to damage. Lactose intolerance appearing after 5–7 days of diarrheal episode warrants active management. Suggestive clinical history of watery, explosive, frequent tools with red perianal area and buttocks coupled with demonstration of reducing substances and a reduced pH of less than 5.5 in freshly passed stools, i.e., within 15–30 minutes is usually enough to establish diagnosis of lactose intolerance.
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Cow’s milk protein intolerance: It presents clinically just like lactose intolerance, although more difficult to diagnose and both may coexist. A useful pointer to distinguish between the two is that while in milk protein intolerance, the child gets diarrhea even on small amount of milk of milk products; in lactose intolerance, the child is able to tolerate reduced amount of milk, especially in milk-based diets. If a child on reduced milk content does not respond, then it is advisable to completely withdraw the milk and milk products.
Mucosal damage: This damage leads to multiple absorptive defects leading to persistence of diarrhea and worsening of nutritional status. It also leads to hypersensitivity to cow’s milk as the ingested milk proteins cause an immune-mediated injury.
Colitis: This is seen in quite a large number of cases and some of these may also be because of unwarranted use of antibiotics (antibiotic colitis).
Malnutrition: While malnutrition prolongs the duration of diarrhea, diarrheal illness itself helps to worsen the nutritional status and thus sets in vicious malnutrition–diarrhea–malnutrition cycle. These children also have multiple vitamin and mineral deficiencies, especially of zinc. It is because of this reason that addition of zinc in therapeutic regimes has helped in the management and prevention of diarrhea.
Occasionally, one might see persistent/chronic diarrhea in early infancy in breastfed babies due to what is known as “allergic proctocolitis”. These babies may be allergic to cow’s milk protein, which may be getting passed on to them through the breast milk of their mother, who is consuming cow’s milk and which may be even in the form of milk in tea. The condition gets further aggravated by multiple courses of antibiotics, which concomitantly causes
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vitamin K deficiency. In these babies excluding cow’s milk in all forms in the mother’s died leads to relief.
RECURRENT DIARRHEA
Some children between 6 months to 5 years of age suffer from recurrent but distinct episodes of acute diarrhea. It is defined as occurrence of six or more episodes per year or more than three episodes in 6 months or more than two episodes in 3 months. Most of the cases are because of poor environmental conditions of these patients and their malnutrition because of which they tend to fall sick repeatedly. Each of these recurrent episodes may need to be dealt with as a fresh episode of acute diarrhea.
Yet another entity is the “Toddlers diarrhea” seen in children of affluent families. These children have frequent stools which become watery by the evening. Fluid diet (milk, fruit juices) seems to aggravate the problem. Putting them on semisolid/solid diet containing some fiber helps. Withdrawing fruit juices, in particular, is quite beneficial.
CHRONIC DIARRHEA
In this condition, the onset of diarrhea is more insidious and usually less watery in nature. The stools are about four to five times per day and usually semisolid. This type of condition is seen more often in children above 3 years of age. Occasionally, the stools may be bulky (even fatty and foul smelling) and in some cases may seem to suggest malabsorption.
The condition of chronic diarrheas is rare. In India, giardiases and tropical enteropathy (due to deprived environmental conditions) have often been seen as the most common causes, although they are more likely to present as recurrent or persistent diarrheas. Now
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reports from different parts of the country indicate higher incidence of celiac disease.
In children aged 6 months to 2 years, the common causes may be giardiasis, cow’s milk allergy, celiac disease. In children above 2 years, the causes may be celiac disease, irritable bowel syndrome, functional causes, and lactose intolerance. Pancreatic insufficiency and cystic diseases are also no longer infrequent causes.
Management
Parents get quite worried when the diarrhea persists beyond 3–5 days and pester the physician for action. As stated above, even in natural history of acute diarrhea, many episodes may last beyond 7 days and hence would not require management on the lines of persistent diarrhea.
Persistent diarrheal episodes, especially those associated with failure to thrive, are the ones which will cause worry to the treating doctor. The difficulty in managing these children arises from the fact that in most cases of persistent diarrhea, a single etiological factor may not be responsible for the particular episode. In fact in majority of the episodes, multiple factors may be operative. Moreover, most of these children are quite moribund requiring urgent therapeutic intervention, even while the diagnostic workup is underway.
Domiciliary Management
It is important to maintain nutritional and hydration status during this period and to avoid drugs (unless absolutely warranted) during this stage. Some children may have clinical and laboratory evidence of lactose intolerance even at such an early stage of diarrheal disease, but as pointed out above, this usually warrants no energetic management. Unless red alert signals are present, these children can be managed at home. Foods like curd, banana, mashed potatoes,
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khichdi, dalia, etc. should be given in large amounts to meet the increased caloric demands during this time together with continued breastfeeding. Low lactose foods like milk-based cereal diets (suji ki kheer, dudh ka dalia, etc.) can help to decrease the lactose load while continuing to provide adequate calories. Addition of oils in the cereal diet can increase the calorie density of food and help in maintaining nutritional balance. Top milk may be required to be restricted (30–50 mL/kg/day) but should not be replaced by soya milk preparation at this age. In fact, the incidence of soya protein intolerance following acute diarrhea is almost 15 times more than that of CMPI. Hence, in no case should soya milk be introduced in the diet of a child with diarrheal episode of less than 14 days duration.
Multivitamins and Minerals Supplement
All children with persistent diarrhea should receive daily supple- mentary multivitamins and minerals for 2 weeks. These supplements should be given in the dose of two recommended dietary allowances (RDAs) every day. For example, a 1-year-old child should be given folate 50 mg, zinc 10 mg, vitamin A 400 mg, iron 10 mg, copper 1 mg and magnesium 80 mg.
Hospital Management
Any child, who presents with a prolonged diarrheal episode along with weight loss, should be hospitalized. These children can have an unpredictable course and may become serious at any time.
Moreover, they would require repeated investigations, which may not be possible in an outpatient situation.
After admission, a detailed history should be taken regarding the onset, duration, character of stools at the onset, and any subsequent change, associated features like anorexia, fever, cough, urine
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frequency, etc. and the management received (drugs, diet, etc.) till then. Physical examination of the child should include assessment of nutritional and hydration status and careful screening for any associated infections [chronic suppurative otitis media (CSOM), pneumonia, and even meningitis].
Preliminary investigations should include stool examination for pus cells, ova, cysts, and red cells and for pH and reducing substances.
A total and differential leukocyte counts, including band counts and blood culture should also be obtained. A urine examination and culture (if required) and an X-ray of chest should be obtained in all cases. Stool cultures have little value as organisms grown in routine culture of stool may not necessarily be enteropathogens and hence their antibiotic sensitivity also has no implication in choosing antibiotics. If available, stool osmolality and electrolytes may be obtained. A stool osmotic gap (total osmolarity = 2 × sodium content) of less than 50 is suggestive of secretory diarrhea, which may require treatment for sepsis and prolonged parenteral nutrition
The stepwise investigation protocol is as suggested below:
Phase I: Clinical history, including specific amounts of fluids ingested per day, physical examination, including nutritional assessment, stool examination (pH reducing substances, smear for white blood cell count, fat, ova, and parasites), stool cultures, stool for Clostridium difficile toxin, and blood studies (complete blood cell count, erythrocyte sedimentation rate, electrolytes, blood urea nitrogen, creatinine). In areas where HIV is highly prevalent, appropriate investigations, including stool examination for isospora should also be carried out.
Phase II: Sweat chloride 72-hour stool collection for fat determination of stool for phenolphthalein, magnesium sulfates, phosphate, and hydrogen (H2) breath tests.
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Phase III: Endoscopic studies, small bowel biopsy, sigmoidoscopy, or colonoscopy with biopsies and barium studies.
In large majority of cases of protracted diarrhea, no single etiological diagnosis is possible. These children are often moribund with fluid, electrolyte, and nutritional imbalance, and their management must be started immediately while the results of investigations are being awaited.
A stepwise treatment approach is as below:
Step 1: If the clinical examination and preliminary investigations do not reveal any evidence of infection then all antibiotics should be stopped. Oral feedings should also be stopped for 24–48 hours and the child should be put on intravenous fluids. By these measures alone, it is quite likely that diarrhea may stop. However, if it does not stop, one may think in terms of persistent gut infection, or a systemic infection, and therefore, systemic antibiotics may be needed.
The antibiotics, which may be helpful in systemic infections, may be a combination of first- or third-generation cephalosporins with aminoglycoside. Occasionally, a fluoroquinolone group of anti biotics may also need to be added. Metronidazole is not indicated in protracted diarrhea in children (contrary to the practice in adults). It can be given (7.5 mg/kg, three times a day orally for 5 days) when the microscopic examination of fresh feces reveals trophozoites of Entamoeba histolytica within red cells or two different antibiotics, which are usually effective for Shigella locally, have been given without clinical improvement.
For giardiasis, metronidazole is given in the dose of 5 mg/kg, three times a day for 5 days if cysts or trophozoites of Giardia lamblia are seen in the feces.
Step 2: If the diarrhea recurs on reintroduction of milk, secondary lactose intolerance may also be considered as a possibility besides
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the systemic infection. The child should be put on a low lactose diet for at least 3–5 days. If the child improves, then the amount of milk and other foods can be increased gradually in the diet.
Figure 1 Chronic diarrhea: management algorithm.
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Prolongation of diarrheal episodes associated with failure to thrive need to be addressed
Persistent colonization of upper small intestine, dietary allergies, decreased host immunity, malnutrition, poor hygiene, food conta
mina tion, and protozoal infections are some common causes of pro trac ted/recurrent/chronic diarrhea
Treatment focuses on providing adequate calories, low lactose load, antibiotics in case of gut or systemic infections, multivitamins, and mineral supplements
When unresponsive, it might be necessary to rule out lactose into
lerance, CMPI, and celiac disease.
kEy mEssAgEs
Step 3: If the child fails to tolerate even “low lactose” feeds, then it is prudent to stop the milk completely because it might also be because of CMPI. The child may then be put on a rice dal, khichdi, soya milk type of diet. If this child improves, then it is recommended that this diet should be given for at least 4–6 weeks, and milk should be reintroduced in their diets in a very careful manner later on. Most of the children might require a milk-free diet for at least 8–12 months.
Step 4: If the child does not respond to any of the above steps, then it may have to be put on intravenous (parenteral alimentation).
Most of these children have multiple vitamin and mineral deficiency besides the PEM. Zinc deficiency is particularly more marked in protracted/chronic diarrhea. It is believed to be a major factor in prolongation of diarrheal episode. Therefore, these children should receive multivitamins and zinc in therapeutic regimes (Figure 1).
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This is due to gluten (gliadin part) induced enteropathy. It is an autoimmune type of chronic inflammatory condition. It is being more frequently diagnosed in India due to wheat becoming a major part of the food menu. It usually manifests in children beyond infancy as the introduction of gluten-containing foods occurs in such children.
The manifestations are chronic diarrhea, failure to thrive, pallor, and short stature as the common features. Various other defects in absorption may also become clinically manifest like iron and B12 deficiency. Sometimes it may present as a case with profuse diarrhea leading to dehydration, acidosis, and shock (celiac crisis).
Provisional diagnosis is by getting positive immunoglobulin A (IgA) isotype serological markers, serum antigliadin (AGA), tissue transglutaminase antibody (tTG), or anti-endomysial antibody (EMA). The AGA is not the preferred test, but in 25% cases, tTG may be negative, and it is in these cases where the AGA may help.
The confirmation is by endoscopy and jejunal biopsy, which show subtotal villous atrophy. This investigation is mandatory.
The management is by complete withdrawal of wheat and other sources of gluten (e.g., rye, barley) for the whole life. Initial relief may tempt to reintroduce wheat in the diet. This can be self-defeating and increases the risk of non-Hodgkin's intestinal lymphomas and