Acute Diarrhea in Children Definition Three or more liquid or watery stools in a 24-hour period are considered as diarrhea. Diarrhea may also be bloody, called dysentery. An episode of diarrhea lasting for less than 14 days is defined as acute diarrhea. Persistent diarrhea is defined as an episode of diarrhea that begins acutely and lasts for at least 14 days. Etiology Intestinal infection is the most common cause of acute diarrhea worldwide. The etiologic pathogen may be virus, bacteria, protozoa, or helminth (Table 1). In spite of the numerous diarrhea-causing organisms, recent studies have shown that the majority of cases in virtually all setting are caused by five organisms: rotavirus, E. coli,Shigella, C. jejuni, and C. parvum. Salmonella and V. cholerae are also important causes of acute diarrhea in some developing countries. Table 1. Enteropathogen responsible for diarrhea. Enteropathogen Bacteria V.cholerae , other Vibrio ETEC EIEC EHEC Shigella, Salmonella spp C. jejuni, Y. enterocolitica Clostridium difficile M. tuberculosis Viruses Rotavirus Adenovirus (type 40,41) Small bowel structured virus Cytomegalovirus Protozoa Giardia lamblia Cryptosporidium parvum Microsporidium spp. Isospora belli Cyclospora cayetanensis Entamoeba histolytica Helminths Strongyloides stercoralis Schistosoma spp. C.philippinensis Trichuris trichiura

Acute watery Dysentery

Persistent

+ + + + + + + -

+ + + + + +

+ + + + +

+ + + +

-

-

+ + + + + +

+

+ + + + + +

+ -

+ +

+ + + +

Epidemiology Acute diarrhea is the second most common illness in children under 5 years of age in the developing world. The attack rate may be up to 3-8 episodes/child/year in developing countries. It is responsible for the death of 3-4 million individuals each year. The morbidity is highest in the age group 6-11 months and the mortality is greatest in infants less than 1 year of age. Most etiologic agents are transmitted from person to person by direct contact through hands contaminated with feces, a common occurrence among children. Light clothing or nakedness and limited water availability are factors favoring this type of transmission in tropical areas. Feces disposed on the ground are a source of contamination of foods and surface water, and of spreading by flies. Pathogenic Enterobacteriaceae, Campylobacter, Yersinia, and Cryptosporidium in human hosts have a zoonotic counterpart. Pathogenesis The pathogenesis of diarrhea can be considered to be due either to (i) increased intestinal secretion and (ii) decreased intestinal absorption. Increased intestinal secretion (secretory diarrhea) Intestinal secretory processes in infective diarrhea are generally activated by secretory enterotoxin. This often occurs in the absence of macroscopic or microscopic intestinal injury. The stool is characteristically watery with a sodium content of about 80 mmol/l. Cholera toxin (CT) is the prototype enterotoxin. This toxin activates adenylate cyclase and results in an increase in intracellular cyclic AMP, which promotes the active secretion of fluid and electrolyte, resulting in watery diarrhea There are other important bacterial enterotoxins, particularly those produced by E. coli. E. coli heat-labile toxins (LT1 and LT2) are a group of proteins that are closely related structurally, functionally and immunologically to CT. Other bacterial enteropathogens that produce LT-like toxins include C. jejuni, S. typhimurium, S. enteritidis, Aeromonas sp., andPlesiomonas sp. E. coli also produces a group of low molecular weight enterotoxins that are heat-stable (ST). ST differs from LT and CT in that it activates guanylate cyclase with an associated increase in intracellular cyclic GMP. Heat stable toxins are also produced by Y. enterocolitica, V. cholerae non-01, and enteroaggregative E. coli. It is now evident that secretory diarrhea may be enhanced by a variety of endogenous secretagogues including prostaglandins, 5-hydroxytryptamine (5-HT) and substance P. Immunological mechanisms may also be important, particularly IgE-mediated hypersensitivity reactions such as local anaphylaxis in the gut. Mast cell products and neurotransmitters are also involved, particularly histamine, 5-HT, prostaglandins, leukotrienes, platelet activating factor and substance P. Decreased intestinal absorption Impaired intestinal absorption is a major mechanism for diarrhea caused by infective enteropathogens and is generally accompanied by macroscopic or microscopic injury to the intestine. Diarrhea due to impaired absorption can be related to impaired fluid, electrolyte and nutrient absorption in the small intestine; osmotic diarrhea due to appearance of incompletely absorbed nutrients in the colon; impaired water and sodium retrieval by the colon due to direct involvement of the colonic absorptive process; or decrease in gut transit times. The stool characteristically contains lower sodium content than in secretory diarrhea (about 30 mmol/l). In dysentery, there are severe inflammatory responses to invasive pathogens like Shigella sp., Salmonella sp., or E. histolytica; the stool may be mucous bloody or contain numerous red and white blood cells. Common enteropathogens Rotavirus. Four serotypes of rotavirus are epidemiologically important. Rotavirus causes patchy damage to the epithelium of the small intestine, resulting in the blunting of the villi.

There is some reduction in the activity of lactase and other disaccharidases, resulting in reduced absorption of carbohydrates, but this is usually of no clinical significance. Intestinal morphology and absorptive capacity return to normal within 2-3 weeks. Enterotoxigenic E.coli (ETEC). Two important virulence factors of ETEC are 1) colonization factors that allow ETEC to adhere to enterocytes of the small bowel, and 2) enterotoxins. ETEC produce heat-labile (LT) and/or heat-stable (ST) enterotoxins which cause secretion of fluid and electrolytes, resulting in watery diarrhea. ETEC do not destroy the brush border or invade the mucosa. Enteropathogenic E.coli (EPEC). The mechanism of EPEC diarrhea is not yet clear. However, it is found that the attachment process of EPEC to the intestinal epithelium causes discrete damage to the microvillous membrane and thus interferes with absorptive surface and disaccharidase activity. Enteroaggregative E.coli (EAggEC). EAggEC adheres tightly to the small intestinal mucosa and produce typical morphological changes; the mechanism by which they cause diarrhea is not clear but a cytotoxin may play a role. Enteroinvasive E.coli (EIEC). EIEC is similar to Shigella both biochemically and serologically. Like Shigella, it penetrates and multiplies within the colonic epithelial cells. Enterohemorrhagic E.coli (EHEC). EHEC produces verocytotoxin (VT) 1 and 2 which are shiga-like toxins and may be responsible for edema and diffuse bleeding in the colon, as well as the hemolytic-uremic syndrome that sometimes develops in children. Shigella spp.Shigella invades and multiplies within colonic epithelial cells, causing cell death and mucosal ulcers. Shigellaseldom invade the bloodstream. The virulence factors include: a smooth lipopolysaccharide cell-wall antigen that may contribute to invasiveness and endotoxic activity and a toxin (Shiga toxin and Shiga-like toxin) which is cytotoxic, neurotoxic, and perhaps also causes watery diarrhea. Campylobacter jejuni (Helicobacter jejuni ). Humans are infected through direct contact with infected animals (poultry, dogs, cats, sheep, and pigs) or their feces, by consumption of contaminated food (esp. chicken) and water, and, occasionally, direct person-to-person spread. C.jejuni probably produces diarrhea by invasion of the ileum and the large intestine. Two types of toxin are produced: a cytotoxin and a heat-labile enterotoxin. The histological changes resemble those of ulcerative colitis. Vibrio cholerae O1 and V. cholerae O139. Both contaminated water and food can transmit cholera; person-to-person spread is much less common. V. cholerae adheres to and multiplies on the mucosa of the small intestine where it produces an enterotoxin which causes the diarrhea. Cholera toxin is closely related to the heat-labile toxin (LT) of ETEC. More recently other enterotoxins have been characterized, including accessory cholera enterotoxin (ACE) and zonular occludens toxin (ZOT), both of which cause fluid secretion into the intestinal lumen. Salmonella (non-typhoid).Salmonella could invade the ileal epithelium. An enterotoxin causes watery diarrhea. When mucosal damage occurs, diarrhea may be bloody. Giardia lamblia.G.lamblia infects the small bowel; the pathogenetic mechanism is unclear but is believed to interfere with absorption and bile acid metabolism. Entameba histolytica.E. histolytica invades the mucosa of the large intestine, where it is thought to elaborate neurohumoral substances that cause intestinal secretion and damage, resulting in an inflammatory type of diarrhea Cryptosporidium. Cryptosporidia are transmitted by the fecal-oral route. Cryptosporidia attach to the microvillous surface of enterocytes where they cause malabsorption owing to the resulting mucosal damage. Clinical Manifestations • Rotavirus. Rotavirus is responsible for up to 25% of diarrhea episodes in children aged 6-24 months visiting treatment facilities, but for only 5-10% of cases in the same age group in the community; prevalent worldwide. Rotavirus is spread by fecal/oral transmission or possibly by airborne droplets. Peak incidence of disease is in cold or dry

seasons. Rotavirus causes watery yellow-colored stools, significant vomiting and mild to moderate fever. Illness ranges from asymptomatic infection (mainly in neonates and adults) to acute dehydrating diarrhea that may lead to death. In Bangladesh, dehydration was observed to be more frequent with rotavirus than with enterotoxigenic E. coliinfections. Respiratory symptoms, suggestive of upper respiratory catarrh, occur in 3035 percent of cases. • Escherichia coli.E.coli cause up to one quarter of all diarrhea in developing countries. Transmission usually occurs through contaminated food (especially weaning foods) and water. Five groups of E. coli are recognized: enterotoxigenic, enteropathogenic, enteroaggregative, enteroinvasive, and enterohemorrhagic. Enterotoxigenic E.coli (ETEC). ETEC is a major cause of watery dehydrating diarrhea in children and adults in developing countries, especially during the warm, wet season. ETEC is the most common cause of diarrhea in travellers from developed to developing countries. The common clinical manifestations include watery diarrhea, anorexia, vomiting and abdominal cramp. The diarrhea is self-limited. Diarrhea produced by heat labile ETEC resembles that due to V. cholerae. Enteropathogenic E.coli (EPEC). In some urban areas, up to 30% of acute diarrhea cases in young infants are attributed to EPEC. EPEC diarrhea occurs predominantly below one year of age. The disease is usually mild self-limited with passage of semi-solid stools but tends to be prolonged and can result in persistent diarrhea, particularly in bottle-fed infants under 6 months of age. Enteroaggregative E.coli (EAggEC). EAggEC has been found in a number of countries. Some strains belong to EPEC serotypes. EAggEC causes fever, vomiting and watery diarrhea in young children, which may become persistent. Some patients may have overt blood in stools. Enteroinvasive E.coli (EIEC). EIEC causes sporadic food- borne cases and outbreaks of diarrhea in all ages worldwide. Polymorphonuclear leukocytes usually present in stools. EIEC causes symptoms which are similar to those of dysentery due to Shigella with frank blood and mucus in the stool. These organisms may also cause septicemic illness. Enterohemorrhagic E.coli (EHEC). EHEC causes sporadic hemorrhagic colitis in North America, Japan and some other areas. Improperly cooked meat serves as a vehicle of transmission; occasionally, direct person to person transmission may occur. EHEC is probably not an important pathogen in developing countries. Illness is characterized by acute onset of cramps, absent or low-grade fever, nausea, vomiting and watery diarrhea that may rapidly become bloody. Hemolytic-uremic syndrome sometimes develops in children. • Salmonella (non-typhoid).Salmonella is not an uncommon cause of gastroenteritis in young children in most of developing countries. In transitional economies, 10% or more of diarrhea in children in urban areas can be due to salmonella infection. Infection most commonly results from the ingestion of contaminated animal products, especially poultry, meat, eggs, and milk. There are over 2,000 serotypes, about 6-10 of which account for most episodes of salmonella gastroenteritis in man.Salmonella usually causes acute watery diarrhea with nausea, cramps, and fever. Salmonella may also cause an exudative diarrhea with leukocytes in the stool, and occasionally dysentery. Many reports of outbreaks of salmonellosis in hospitals and communities were associated with serious morbidity and mortality, especially among the very young. Many salmonella infections are asymptomatic and carriers pose difficult problems in the control of the infections in communities. Strains resistant to ampicillin, chloramphenicol, and cotrimoxazole are now found worldwide. These have added a serious dimension to the problem of management and control of salmonella infections. • Shigella spp.Shigella cause 10-15% of acute diarrhea in children under 5 years and are the most common cause of dysentery in children. Spread is often by person-toperson contact since the infectious dose is low (10 to 100 organisms). Food borne and

waterborne transmission also occurs. Peak incidence is in the warmer seasons. Shigella are subdivided into 4 serogroups: S. flexneri, the most common serogroup in developing countries; S. sonnei, the most common in developed countries; S. dysenteriae type 1, which causes epidemics of severe disease with high mortality; S. boydii is less common. The incubation period is usually 2-3 days and rarely longer than 1 week. S. sonnei causes mild diarrhea, dysentery. S. flexneri or S. dysenteriae produce severe infections i.e. high fever, marked toxemia, severe abdominal pain, persistent urge to defecate, and stools that consist mainly of watery mucus, pus and blood. Fever, abdominal pain and vomiting may precede the onset of diarrhoea by many hours and may suggest the diagnosis of appendicitis. In young children, early symptoms must be differentiated from intussusception. In the tropics, bacillary dysentery may sometimes strike with catastrophic severity and lead to prostration and circulatory collapse, disseminated intravascular coagulation, acute renal failure and hemolytic-uremic syndrome which can lead to death. Shigellosis is particularly severe in malnourished, non-breast-fed infants, old people, and debilitated persons. Antibiotic resistance is frequent. • Campylobacter jejuni (Helicobacter jejuni) . C. jejuni causes 5-15% of diarrhea in infants worldwide. It is spread feco-orally from man to man or animal to man. In developing countries the peak incidence occurs below the age of 12 months. Diarrhea may be watery but in one-third of cases dysenteric stools with blood and mucus appear after a day or two. Vomiting is not common and fever is usually low. It may cause disseminated infection in malnourished infants or patients with hepatic dysfunction, malignancy, diabetes mellitus, renal failure, or immunosuppression. • Vibrio cholerae O1 and O139. Cholera is endemic in many countries of Africa and Asia. In endemic areas, it may account for 5-10% of hospitalized patients with diarrhea in all age groups. However, it occurs most often in children 2-9 years of age, and many cases are severe. In newly-affected areas, young adults are most often infected. V. cholerae has two biotypes (El Tor and classical) and two serotypes (Ogawa, Inaba). Biotyping and serotyping are not important for treatment and control. During the last few years, outbreaks due to tetracycline-resistant strains of V. cholera have occurred in a few countries. Diarrhea may be mild or very severe with profuse watery stools. Dehydration, shock, and death can occur in a few hours in fulminant cases. • Giardia lamblia. G.lamblia has a worldwide distribution, the prevalence of infection in young children approaching 100% in some areas. Children aged 1-5 years are most commonly infected. Giardia infections are food- borne, water- borne, or spread by the fecal-oral route; the latter occurs particularly in children living in crowded circumstances or attending day-care centers. Host parasite interaction varies with age, nutritional status, endemicity and immune status. Patients with agammaglobulinemia are particularly prone to infection. Flattening of the intestinal epithelium is seen in severe cases. In areas of high endemicity, giardiasis may present as asymptomatic infection or as chronic, persistent diarrhea with or without evidence of malabsorption. In areas of low endemicity, giardiasis may occur in epidemic outbreaks with symptoms arising within 5-8 days after exposure and presenting as acute diarrhea associated with nausea, epigastric discomfort and anorexia. It can cause acute or persistent diarrhea, sometimes malabsorption, with fatty stools and often abdominal pain and bloating. However, the vast majority of infections are asymptomatic. This makes it very difficult to determine whether Giardia is actually the cause of a diarrheal episode. • Entameba histolytica . Prevalent rates of E. histolytica infection vary widely but its distribution is worldwide. The incidence of disease increases with age; most episodes are in adult males. About 90% of infections are asymptomatic and are caused by strains

of E. histolytica that are non-pathogenic (E. dispar). The diagnosis of invasive disease usually requires identification of hematophagous trophozoites in feces or colonic ulcers. Symptomatic amebiasis ranges from persistent mild diarrhea to fulminant dysentery to liver abscess. In more serious infections, diarrhea is more overt and persistent. The stools characteristically contain an excess of clear mucus with variable amounts of blood. Fever and constitution disturbance may not be very evident. The most severe form of the disease may have an acute onset and simulate bacillary dysentery. • Cryptosporidium . In developing countries, cryptosporidia may account for 5-15% of childhood diarrhea. The infection is usually symptomatic in infants but asymptomatic in older children and adults. Illness is characterized by acute watery diarrhea which is nonsevere and self-limited except in immunodeficient patients. Cryptosporidia are a common cause of watery diarrhea in immunosuppressed patients, particularly those with acquired immune deficiency syndrome (AIDS). Types of Fluid for Rehydration Therapy Oral rehydration therapy (ORT) is now recognized as a major scientific advance of practical importance, a powerful tool for the replacement of dehydration and decrease in mortality due to acute diarrhea, an invaluable public health weapon, an essential component of primary care and a useful entry point for other child survival interventions. • Oral rehydration salt solution (ORS). The ORS recommended by WHO and UNICEF contains glucose 20 g, sodium chloride 3.5 g, sodium bicarbonate 2.5 g or more recently trisodium citrate 2.9 g, and potassium chloride 1.5 g to be mixed in one litre of water. Oral rehydration therapy (ORT), administered at home with the onset of diarrhea, has been shown not only to decrease mortality, but also to minimize the adverse nutritional effects of diarrhea, possibly due to indirect benefit from hydration. However, careful blinded studies have shown that the present glucose-based ORS formulation neither reduces the magnitude of diarrhea in terms of volume and frequency of stools nor the duration of illness. This causes a necessity to search for other formulations of oral rehydration solution. Amino acids including glycine, L-alanine, L-glutamine and dipeptides of neutral amino acids were studied for their enhancing properties in sodium and chloride absorption. Unfortunately, it was discovered that these amino acid-based ORS did not offer clinical advantage over WHO-ORS for acute non-cholera diarrhea. • Cereal-based ORS. Recent research findings testify that replacing glucose or sucrose by rice or other cereals (30 - 50 g) in ORS results in a diminished volume of diarrhea, and the duration of illness is also reduced. A meta-analysis showed that ricebased ORS was more effective than WHO-ORS in reducing stool output during the first 24 hours of treatment in adults and children with cholera. Rice-based ORS, however, did not exert significant reduction in stool output comparing to WHO-ORS in non-cholera diarrheic patients. Field studies have shown that the nutritional effects of diarrheal episodes are lessened when cereal-based ORS is used with the onset of diarrhea. Recently, ricepowder salt solution (RPSS) containing rice-powder 30 g/l and salt 3.5 g/l was evaluated in infants and young children. It was found that RPSS was also more effective than ORS in terms of reduced stool frequency, lower volume of stool output and shorter duration of diarrhea. Treatment of Acute Diarrhea Treatment of acute diarrhea consists of 1) water and salt replacement, 2) nutritional management, and 3) antimicrobial agents. 1. Water and salt replacement 95% of acute watery diarrhea can be successfully and optimally treated using only oral

rehydration therapy (ORT) and continued feeding. The best and easiest way to replace the water and salt that is lost from the body during diarrhea is by mouth. The mixture for this is a solution made from ORS or cereal-based ORS. In a very small number of cases when the dehydration is severe or the patient vomits very frequently, ORS solution will be not enough; these cases need intravenous (IV) fluids. Criteria for assessment of dehydration are shown in Table 2. Table 2. Assessment of dehydration* DIARRHEA

Less than 4 liquid 4-10 liquid stools stools per day per day

VOMITING THIRST URINE

None Normal Normal

CONDITION

Well, alert

EYES

Normal

MOUTHand TONGUE BREATHING

Wet

SKIN

Pinch goes back quickly Normal NO DEHYDRATION

FONTANELLE Decide

Treat

Normal

Use plan A

More than 10 liquid stools per day Some Very frequent More than normal Unable to drink Small amount, dark No urine for 6 hours Unwell, sleepy or Very sleepy, irritable floppy, unconscious, having fits or seizures Sunken Very dry and sunken Dry Very dry Faster than normal Very fast and deep Pinch goes back Pinch goes back slowly very slowly Sunken Very sunken Two or more of Two or more of these signs, there these SIGNS, isDEHYDRATION there isSEVERE DEHYDRATION Use plan B Use plan C

* Adapted from WHO/CDD/SER 80.2 Rev 2, 1990. Plan A. Use plan A for diarrhea with no or mild dehydration where treatment could be done at home. The aims of this plan are 1) to prevent dehydration, and 2) to continue feeding. Give mother enough ORS packets to last 3 more days and tell the mother: 1) To increase fluids and continue feeding the child, give : 50-100 ml for child 210 years-adults

of rehydration solution after every diarrheic stool until there are less than 4 loose stools per day. Give more than normal amounts of breast milk or bottle milk and other liquids. If the child is >4 months old give other foods also.

2) To watch for the signs of dehydration and other problems: Explain to the mother that she should take her child to a health worker if the child does not get better in 3 days or develops one of the following. : Many watery stools : Eating or drinking poorly : Repeated vomiting : Fever : Marked thirst : Blood in stool Plan B. Use plan B for diarrhea with some dehydration. The aims of treatment are 1) to treat the dehydration, 2) to prevent dehydration from coming back, and 3) to continue feeding. 1. Assess degree of dehydration (Table 2) and determine how much ORS solution is needed (Table 3) to treat the dehydration in the first 4-6 hours. 2. After 4-6 hours: determine signs of dehydration. 3. After the signs of dehydration have gone. : Give maintenance ORS solution to prevent dehydration from coming back. : Give the needed amount of ORS solution after every diarrheic stool until there are less than 4 loose stools per day. : Feed the child and give other fluids. Feed frequently (5-7 times a day) during diarrhea until normal stool, then give one extra meal each day for a week. 4. On home discharge, give enough ORS packets to last 3 more days and ask the mother to come back then if the diarrhea has not stopped. Table 3. Plan B, How much ORS to give. (All volumes in ml)*

* These are guidelines only. If the patient wants more ORS solution, give more. If the eyelids become puffy, stop giving ORS solution and continue giving other liquids; start ORS solution again when puffiness is gone and if diarrhea continues. Adapted from WHO/CDD/SER 80.2 Rev 2, 1990.

Plan C. Use plan C for diarrhea with severe dehydration. The aims of treatment are 1) to start treating the dehydration, 2) to refer the child immediately for additional treatment, and 3) to continue feeding. Severe dehydration needs special treatment including IV fluid quickly. If you can not give IV fluid and the child can drink, start ORS solution as in plan B. Give the mother some prepared ORS solution and tell her to continue giving it on the way to the health care center, as long as the child can drink. If you can give IV, use guidelines for rehydration therapy (Table 4)and maintenance therapy. (Table 5) Table 4. Guidelines for rehydration therapy* Age group

Type of fluid I.V. Ringer's Lactate FOLLOWED BY:

Infants

Older children and adults

Volume of fluid Time of (per kg body weight) administration 30 ml/kg Within 1 hour

I.V. Ringer's Lactate FOLLOWED BY:

40 ml/kg

Within next 2 hours

ORS Solution

40 ml/kg

Within next 3 hours

I.V. Ringer's Lactate

110 ml/kg

Within 4 hours initially as fast as possible until radial pulse is palpable

* Adapted from WHO/CDD/SER 80.2 Rev 2, 1990. Table 5. Guidelines for maintenance therapy* Amount of diarrhea Type of fluid

Administration

Mild diarrhea (not ORS By mouth at home more than one stool every 2 hours or longer, or less than 5 ml stool per kg per hour) Severe ORS By mouth at diarrhea (more than treatment facility one stool every 2 hours, or more than 5 ml of stool per kg per hour) Severe diarrhea with Treat as for Severe Dehydration recurrence of signs of dehydration * Adapted from WHO/CDD/SER 80.2 Rev 2, 1990.

Amount of fluid 100 ml/kg body weight per day until diarrhea stops1

Replace stool losses volume for volume; if not measurable give 10-15 ml/kg body weight per hour

2. Nutritional management Nutritional management for the child with diarrhea is more or less similar to that for the normal child (Table 6). Many studies confirmed that continued feeding, including breastfeeding, during diarrhea, reduced the adverse effects of the disease on nutritional status. In addition, there was no need, in the majority of cases, to dilute milk feeds or to use lactose-free formula during acute diarrhea. Table 6. Nutritional management* Child's age

Breast feeding

Other foods

Birth 4 months

Start at birth. Feed whenever the baby wants Continue

6 months

Continue

One year and older

Continue up to at least 2 years of age

None, unless not enough breast milk Add other soft, mashed foods two times a day Add other foods** four times a day All foods four to six times a day

* Adapted from "Guidelines for Nutrition Training of Primary Health Care Workers and Other Community Workers", WHO unpublished document NUT/80.2, 1980. ** These foods should be "energy rich". Most staple foods (e.g., cereals, roots, tubers, stems) do not contain enough energy per unit weight for infants and young children. Where possible, some oils, fats or sugars should be added. The diet should be varied with addition of legumes, animal foods, and fresh fruits and leafy green vegetables. 3. Antimicrobial agents for diarrhea In general, it is recommended that antibiotics are indicated for the more severe dysenteric illnesses. In acute watery diarrhea, use of antibiotics should be restricted to severe cases of cholera. Other situations in which antibiotic therapy may prove useful are shown in table 7. With dysentery, it is reasonable to treat it as suspected shigellosis, because it is the most common cause of dysentery. Antibiotics are also required in salmonella diarrhea in very young children or seriously debilitated or malnourished individuals who manifest evidence of invasive salmonellosis. The quinolones, particularly the fluoroquinolones, have been shown to be effective in travellers' diarrhea. However, there is some controversy about the ethics of using these drugs in travellers' diarrhea because of the risk of contributing to antibiotic resistance and the risk of suffering from a serious side effect of antibiotics which have been given for a mild and self-limiting disease.

Table 7. Type of diarrhea in which antibiotics may prove useful Type of diarrhea Dysenteric shigellosis Amebiasis Typhoid Cholera Giardiasis Enterotoxigenic E. coli Campylobacter/Yersinia spp. Cyclospora/Microsporidium Non-bacteremic salmonellosis Aeromonas/Plesiomonas spp. Cryptosporidiosis Enterohemorrhagic E. coli

Role of antibiotics Required Required Required Useful Useful Useful Useful Useful Controversial Controversial Controversial May be harmful

4. Others Vitamin A. Studies have shown that diarrhea morbidity and mortality recurred significantly more often in children with xerophthalmia. Vitamin A supplementation (8333 IU or 8.7 m mol weekly) to preschool children who had vitamin A deficiency can reduce mortality associated with diarrhea. Young children with measles complicated with pneumonia and diarrhea who received vitamin A 200,000 IU (60 mg)/day for 2 consecutive days (orally) recovered significantly more rapidly from both pneumonia and diarrhea than those without vitamin A. Vitamin A also reduces measles mortality. Zinc. A study in India showed that giving zinc to patients with acute diarrhea could reduce stool frequency by around 30% in children older than 6 months. It is, however, unclear whether such therapy will benefit only undernourished or also well nourished children. Anti-diarrheal drugs and anti-emetics. These agents, though commonly used, have no practical benefit and areNEVER indicated for the treatment of acute diarrhea in children. Their use wastes family resources and may delay appropriate treatment with fluids and food. Products in this category include: kaolin-pectin, diphenoxylate, loperamide, bismuth subsalicylate, chlorpromazine. Smectite was shown to have a modest impact on duration of diarrhea but no effect on total stool output and is not recommended for the routine management of diarrhea in children. Recent research has been focused on racecadotril which is an enkephalinase inhibitor with an antisecretory activity. However, its role in acute watery diarrhea in children is still unclear and needs further investigation. Prevention Effective preventive measures aim to reduce morbidity and mortality of diarrhea as shown in Table 8. Rotavirus vaccine development is still in progress since the tetravalent rhesushuman reassortant rotavirus vaccine (RRV-TV) was withdrawn after licensing because it may cause intussusception in infants. Shigella vaccine is also under development as well as some available vaccine, such as cholera vaccine, to improve their efficacy and tolerability.

Table 8. Outcome of interventions to prevent diarrhea Outcome High effectiveness and feasibility

Uncertain effectiveness, feasibility or cost

Ineffective, limited feasibility or high cost

Interventions Promotion of breastfeeding Improving weaning practices Improving water supply and sanitation Promoting personal and domestic hygiene Rotavirus immunization Cholera immunization (in some circumstances) Measles immunization Preventing low-weight births Using growth charts Increasing child spacing Vitamin A supplementation Improving food hygiene Endemic control Control of zoonotic reservoirs Enhancing lactation Supplementary feeding programmes Chemoprophylaxis Fly contol

Summary Four million individuals die from diarrhea each year, the majority of whom are children under 5 years. Oral rehydration therapy is the major tool for the replacement of dehydration and decrease in mortality due to acute diarrhea. Cereal-based ORS and ricepowder salt solutions have been shown to be more effective than WHO-ORS, in terms of lesser stool frequency, lesser stool output, and shorter duration of diarrhea. Antibiotics should be used only in patients with bloody diarrhea or suspected cholera. Other antidiarrheal drugs and anti-emetics are never indicated for the treatment of acute diarrhea in children. Morbidity and mortality from acute diarrhea are effectively reduced by breastfeeding, measles immunization and hand-washing practices. References • Black RE, Lopez de Romana G, Brown KH, et al. Incidence and etiologic of infantile diarrhea and major routes of transmission in Huacar, Peru. Am J Epidemiol 1989;129:785-99. • Black RE, Merson MH, Rahman ASMM, et al. A two-year study of bacterial, viral, and parasitic agents associated with diarrhea in rural Bangladesh. J Infect 1980;142:6604. • Carpenter CC, Greenough WB, Pierce NF. Oral-rehydration therapy-the role of polymeric substrates. N Engl J Med1988;319:1346-8. • Clemens JD, Stanton BF, Chakraborty J, et al. Measles vaccination and childhood mortality in rural Bangladesh. Am J Epidemiol 1988;128:1330-9. • Elliott K, Attawell K, Wilson R, Hirschhorn N, Greenough III WB, Khin-Maung-U, eds. Cereal based oral rehydration therapy for diarrhoea. London: Pegasus Press; 1990. • Farthing MJ. Novel targets for the pharmacotherapy of diarrhoea: a view for the millennium. JGastroenterol Hepatol2000;15 Suppl:38-45. • Figueroa G, Araya M, Ibanez S, et al. Enteropathogens associated with acute diarrhea in hospitalized infants. J Pediatr Gastroenterol Nutr 1986;5:226-31. • Gore SM, Fontaine O, Pierce NF. Efficacy of rice-based oral rehydration. Lancet 1996;348:193-4.

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Gore SM, Fontaine O, Pierce NF. Impact of rice based oral rehydration solution on stool output and duration of diarrhoea: meta-analysis of 13 clinical trials. BMJ 1992;304:287-91. Leksomboon U, Echeverria P, Suvongse C, Duangmani C. Viruses and bacteria in pediatric diarrhea in Thailand: a study of multiple antibiotic-resistant enteric pathogens. Am J Trop Med Hyg 1981;30:1281-90. Hussey GD, Klein M. A randomized controlled trial of vitamin A in children with severe measles. New Engl J Med1990;323:160-4. Molla AM, Ahmed SM and Greenough WB III. Rice based oral rehydration solution decreases stool volume in acute diarrhoea. Bull WHO 1985;63:751 -6. Molla AM, Molla A, Rohde J, Greenough III WB. Turning off the diarrhoea: the role of food and ORS. J Pediatr Gastroenterol Nutr 1989;8:81-4. Martinez H, Shekar M, Latham M. Vitamin A supplementation and child mortality. Lancet 1986;2:451. Murphy TV, Gargiullo PM, Massoudi MS, et al. Intussusception among infants given an oral rotavirus vaccine. N Eng J Med 2001;344:564-72. Nalin DR , Russel R. Vitamin A, xerophthalmia, and diarrhoea. Lancet 1980;1:1411. Pierce N, Fontaine O. Does smectite have antidiarrheal activity? J Pediatr Gastroenterol Nutr 1994;18:505-6. Rahmathullah L, Underwood BA, Thulasiraj RD, et al. Reduced mortality among children in southern India receiving a small weekly dose of vitamin A. New Engl J Med 1990; 323:929-35. Sabchareon A, Chongsuphajaisiddhi T, Kittikoon P, Chanthavanich P. Rice-powder salt solution in the treatment of acute diarrhea in young children. Southeast Asian J Trop Med Public Health 1992;23:427-31. Sazwal S, Black RE, Bhan MK, Bhandari N, Sinha A, Jalla S. Zinc supplementation in young children with acute diarrhea in India. N Eng J Med 1995;333:839-44. Snyder JD, Merson MH. The magnitude of the global problem of acute diarrhoeal disease: a review of active surveillance data. Bull World Health Organ. 1982;60:60513. Sommer A, West KP. Vitamin A supplementation and child mortality. Lancet 1986;2:451-2. Vijayaraghavan K, Radhaiah G, Prakasam BS, et al. Effect of massive dose vitamin A on morbidity and mortality in Indian children. Lancet 1990;336:1342-5. WHO Child and Adolescent Development. The evolution of diarrhoeal and acute respiratory disease control at WHO, achievements 1980-1995 in research, development, and implementation. WHO/CHS/CAH/99.12,1999. WHO Control of Diarrhoeal Diseases Programme. A manual for the treatment of diarrhoea for use by physicians and other senior health workers. WHO/CDD/SER 80.2 Rev.2, 1990. WHO Diarrhoeal Diseases Control Programme. Guidelines for the trainers of community health workers on the treatment and prevention of acute diarrhoea. WHO/CDD/SER/80.1, 1980. WHO Diarrhoeal Diseases Control Programme. Recent advances in the development of non-antimicrobial antidiarrhoeal agents. In: Report of the Second Meeting of the Scientific Working Group on drug development and management of acute diarrhea. WHO/CDD/DDM/82.3, 1982. WHO Diarrhoeal Diseases Control Programme. The invasive diarrhea: a review of diarrhea due to Shigella species, Campylobacter jejuni, and enteroinvasive Escherichia coli. In: Report of the second meeting of the Scientific Working Group on Bacterial enteric infections: microbiology, epidemiology, immunology, and vaccine development. WHO/CDD/BEI/82.4, 1982. WHO Diarrhoeal Diseases Control Programme. The treatment and prevention of acute diarrhoea practical guidelines. 2nd ed. Geneva : WHO; 1989.