INFECTIOUS DIARRHEA

EPIDEMIOLOGY

According to the World health organization (WHO), diarrheal diseases in children remain second leading cause of death in children under 5 year of age. An estimated 1.7 billion cases of diarrhea are reported per year in children. Among these reported cases 760,000 cases die per year.⁽¹⁾

In Pakistan 100-150 children die every day as a result of diarrhoeal-related illnesses.^(2,3) Between 60 and 75 million people are affected by diarrhoeal-related illnesses annually, and 60 per cent of under five deaths are due to water- and sanitation-related diseases.⁽³⁾

In Pakistan, every child on average suffers from 5-6 episodes of diarrhea per year. The reported prevalence of diarrhea in Punjab is found as 7.8%.⁽⁴⁾

PATHOPHYSIOLOGY:

Adequate fluid balance in humans depends on the secretion and reabsorption of fluid and electrolytes in the intestinal tract; diarrhea occurs when intestinal fluid output overwhelms the absorptive capacity of the gastrointestinal tract. The 2 primary mechanisms responsible for acute gastroenteritis are:

• Damage to the villous brush border of the intestine, causing malabsorption of intestinal contents and leading to an osmotic diarrhea, and
• The release of toxins that bind to specific enterocyte receptors and cause the release of chloride ions into the intestinal lumen, leading to secretory diarrhea.⁽⁵⁾

Even in severe diarrhea, however, various sodium-coupled solute co-transport mechanisms remain intact, allowing for the efficient reabsorption of salt and water. By providing a 1:1 proportion of sodium to glucose, classic oral rehydration solution (ORS) takes advantage of a specific sodium-glucose transporter (SGLT-1) to increase the reabsorption of sodium, which leads to the passive reabsorption of water. Rice and cereal-based ORS may also take advantage of sodium-amino acid transporters to increase reabsorption of fluid and electrolytes.⁽⁵⁾

Diarrhea can be subdivided based upon pathophysiology, although much overlap exists.⁽⁶⁾ Common categories include:

• Osmotic
• Secretory
• Motility-related
• Inflammatory

OSMOTIC: Osmotic diarrhea occurs when an absorbable solute, such as lactose, is not absorbed properly. This results in a higher than normal concentration of the solute in the gut lumen, altering the gradient of water absorption toward fluid retention in the intestinal lumen. Enteric infections that cause damage to intestinal epithelial cells leading to malabsorption may cause diarrhea with an osmotic component. Rotavirus and shigella are examples. Rotavirus selectively invades mature enterocytes causing a disruption of absorptive capacity. Shigella produces a "shiga" toxin,⁽⁷⁾ which can cause villous cell destruction leading to malabsorption.

SECRETORY: Secretory diarrhea occurs when there is active secretion of water into the gut lumen. A classic example is cholera, although there are many other infectious and non-infectious causes. Examples of the latter include those mediated by gastrointestinal peptides (such as vasoactive intestinal peptide and gastrin). Certain substances, such as bile acids, fatty acids, and laxatives, also can produce a secretory diarrhea, as can congenital problems (e.g. congenital chloride diarrhea).

Several bacterial infections of the gastrointestinal tract produce diarrhea secondary to preformed toxins. Examples include the enterotoxins produced by Clostridia perfringens and Clostridia difficile, and the Shiga-like toxins of Escherichia coli, Staphylococcus aureus, and Shigella species.^(8,9)

Viral enterotoxins also have been described. As an example, rotavirus produces a viral enterotoxin, the non-structural glycoprotein (NSP4). NSP4 causes calcium-dependent transepithelial chloride secretion from the crypt cells, with a resultant secretory diarrhea.

MOTILITY RELATED: Motility disorders are relatively uncommon causes of acute diarrhea. Changes in gastrointestinal motility can influence absorption. Hypomotility, or the severe impairment of intestinal peristalsis, results in stasis, with subsequent inflammation, bacterial overgrowth, and secondary bile acid deconjugation and malabsorption. In contrast, hypermotility, such as in irritable colon of infancy, can lead to diarrhea secondary to inadequate time for absorption.

INFLAMMATION: Diarrhea can be caused by intestinal inflammation. The inflammatory process causes destruction of villous cells and / or dysfunction of the transporters, leading to loss of fluids and electrolytes. The inflammatory process also can lead to exudation of mucus, protein, and blood into the gut lumen.

Some pathogens (e.g. vibrio cholera) cause primarily secretory diarrhea with minimal inflammatory component, whereas other pathogens (e.g. salmonella and clostridium difficile) cause primarily inflammatory responses, and others (e.g. shigella) typically have both components .

Intestinal inflammation can also be caused by chronic diseases, such as inflammatory bowel disease and celiac disease. Diarrhea in these disorders is multifactorial but is due in part to the mucosal inflammation, which leads to malabsorption. Malabsorbed substances produce an osmotic load in the gut lumen resulting in diarrhea.

TRANSMISSION⁽¹⁰⁾:

Practically all of the more common childhood diarrhoeal diseases caused by pathogenic bacteria and viruses are transmitted via the faecal-oral route. The pathogens discharged in the faeces of an infected person may enter the body of another susceptible person through the mouth. This may occur among children ingesting food or water contaminated with human excreta.

Direct transmission among persons in close contact is also possible. Such transmission could occur via unclean hands, or through contaminated objects such as bed linen, kitchen utensils, and tableware. Flies and cockroaches play a role as vectors of the infectious agents of faecal origin.

NATURAL HISTORY⁽¹¹⁾:

The natural history of intractable diarrhoea is related to the primary intestinal disease. Food intolerance generally resolve in few weeks or months, as does autoimmune enteropathy, when appropriate immunosuppression is started. Children with motility disorder show more severe, long lasting symptoms but a less severe course, whereas those with structural enterocyte defects never recover, undergo a more severe course, generally needing parenteral nutrition and often become candidates for intestinal transplant.

SIGN AND SYMPTOMS:

Diarrhea may be watery or contain blood. Stool may float which may indicate that there is increased fat present in the stool. Diarrhea may also be accompanied by:

• Urgency with bowel movements, which means that children feel that they have to get to the bathroom immediately
• Abdominal pain and / or bloating
• Rectal pain
• Nausea and / or vomiting
• Weight loss
• Fever

Individuals with diarrhea are at risk for dehydration, which occurs when someone is unable to take in sufficient fluid orally to meet their daily requirements and compensate for losses in their stools. Signs of dehydration include:

• decrease in urine output / wet diapers
• dry lips and mouth
• lack of tears when crying
• increased irritability and fussiness
• increased sleepiness / decreased energy level

DIAGNOSTIC TESTS:

CLINICAL ASSESSMENT: The assessment of the child with diarrhea can be divided into four components to guide clinical management:

• Classification of the type of diarrheal illness
• Assessment of hydration status
• Assessment of nutritional status
• Assessment of co-morbid conditions

CLASSIFICATION OF DIARRHEA: The assessment of a child with diarrhea should include a history of the duration, frequency, and character of the diarrhea, as well as an assessment of the stool. Patients can be classified as having:

• Acute watery diarrhea: loose or watery stools at least three times in a 24 hour period.
• Invasive diarrhea: (synonymous with dysentery) gross blood (by history or inspection) in the stool of <14 days duration, typically accompanied by fever. It is usually the result of exudative inflammation of the distal small bowel and colonic mucosa in response to bacterial invasion.
• Persistent diarrhea: loose, watery, or bloody stools of ≥14 days.

Other characteristics of the diarrhea and associated symptoms may be clues as to the etiology. As an example, the diagnosis of cholera is suggested by a short history (usually less than 24 hours) of vomiting and passage of voluminous watery diarrhea, which may have a characteristic rice-water appearance, associated with severe dehydration. It is important to distinguish cholera from other causes of acute watery diarrhea because patients with severe cholera may have more rapid fluid losses and typically benefit from antibiotic therapy.

HYDRATION STATUS: The degree of dehydration should be assessed at presentation based on physical signs and symptoms. Several studies have demonstrated that using a combination of three to four physical signs reliably predict dehydration of 3 to 5 percent or greater.^(12-14) The World Health Organization (WHO) has issued recommendations for assessing dehydration based on four clinical signs that have been associated with dehydration in several studies.^(12-14)

TABLE 1: WHO guidelines for assessment of dehydration

Clinical feature	Predicted degree of dehydration
	None (<5 percent)	Some dehydration (5-10 percent)	Severe dehydration (>10 percent)
General appearance	Well, alert	Restless, irritable	Lethargic or unconscious
Eyes	Normal	Sunken	Sunken
Thirst	Drinks normally, not thirsty	Thirsty, drinks eagerly	Drinks poorly or unable to drink
Skin pinch	Goes back quickly	Goes back slowly	Goes back very slowly
Estimated fluid deficit	<50 mL/kg	50-100 mL/kg	>100 mL/kg

Following the initial assessment, ongoing fluid losses should be estimated based on the volume of emesis and stool. These assessments are essential for determining the volume, route, and pace of rehydration therapy needed.

NUTRITIONAL STATUS: Recurrent diarrhea in childhood is associated with malnutrition, which contributes to delays or irreversible deficits in physical and cognitive development. Children with acute diarrhea and malnutrition are at increased risk for developing fluid overload and heart failure during rehydration. The risk of serious bacterial infection is also increased. As a result, such children require an individualized approach to rehydration, nutritional care, and antibiotics.

PHYSICAL EXAMINATION: Assessment of a child with acute diarrhea should include evaluation of the following:

• Temperature: Fever is common in the setting of diarrheal illness. The presence of fever or hypothermia in a patient with watery diarrhea should also raise clinical suspicion of a comorbid illness. Fever in areas where malaria is endemic should prompt appropriate diagnostic evaluation.
• Respiratory tract: Tachypnea can be a sign of pneumonia in the setting of cough or difficulty breathing; the WHO uses the following parameters: infants <2 months: >60 breaths / min; infants 2 to 12 months: >50 breaths / min; children 1 to 5 years: >40 breaths / min; children ≥5 years: >20 breaths / min.⁽¹⁵⁾ Children with dehydration should be reassessed for pneumonia following initial rehydration. In some cases, a chest radiograph may be required for diagnosis of pneumonia, particularly in severely malnourished and dehydrated patients.^(16-18)
• Abdomen: Abdominal pain out of proportion to typical gastroenteritis raises the possibility of a surgical emergency. Among patients with severe dysentery due to Shigella, intestinal obstruction was reported in 2.5 percent of hospitalized cases in one series.⁽¹⁹⁾ Intussusception may present with acute bloody diarrhea and severe intermittent abdominal pain; in some cases a cylindrical abdominal mass is palpable. In young children, appendicitis may also present with diarrhea and abdominal pain.
• Central nervous system: Moderate dehydration can lead to irritability; severe dehydration can lead to lethargy and coma. Encephalopathy and / or seizures can occur in the setting of severe disease due to Shigella, and less commonly in systemic Salmonella infection. The differential diagnosis of seizures in a child with diarrhea includes hypoglycemia, hyponatremia, hypernatremia, encephalopathy, meningitis, and febrile seizures. Meningeal signs may be absent in infants with meningitis; therefore any abnormal neurologic findings should raise suspicion for meningitis.

DIAGNOSTIC STUDIES: Most children with acute diarrhea do not require laboratory testing, although in complex cases some laboratory studies may be useful. Patients with seizures or altered consciousness should have glucose and electrolyte assessment if possible. Children with suspected pneumonia, sepsis, meningitis, urinary tract infection, or HIV infection should have the relevant investigations. Imaging studies are warranted for patients with acute abdominal findings on physical examination.

Microscopy can be used for presumptive diagnosis of two important causes of gastroenteritis. Cholera may be diagnosed using dark field microscopy to detect motile Vibrios, which appear as "shooting stars". In the setting of acute bloody diarrhea, direct microscopic evidence of Entamoeba trophozoites containing red blood cells is a sufficient diagnostic finding warranting treatment for amoebic dysentery (rather than shigellosis).

Microbiology laboratory evaluation, when available, is warranted for patients with invasive diarrhea who do not respond to empiric antibiotic therapy. Other judicious uses of microbiology data include surveillance to detect epidemics and evaluation of antimicrobial susceptibility patterns of selected pathogens.

TREATMENT OPTIONS:

ACUTE WATERY DIARRHEA:

FLUID AND ELECTROLYTES: Fluid management consists of two phases: replacement and maintenance. The goal of replacement therapy is to replenish deficits in water and electrolytes lost. The replacement phase is continued until all signs and symptoms of diarrhea are absent and the patient has urinated; ideally this is achieved during the first four hours of therapy. Maintenance therapy counters ongoing losses of water and electrolytes; this phase is continued until all symptoms resolve.

Most children with acute diarrhea should be treated with Oral Rehydration Solution (ORS), a mixture of water, salts, and glucose, in both the replacement and maintenance phase. For children with severe dehydration, the replacement phase should begin with intravenous fluids (IVF).

Stool potassium losses commonly result in hypokalemia. This most often manifests with muscle weakness, though in more severe cases may be complicated by paralytic ileus and / or arrhythmia. Potassium losses are generally replaced using ORS, though some isotonic intravenous fluids contain higher amounts of potassium to replace these losses.

WORLD HEALTH ORGANIZATION (WHO) MANAGEMENT OF ACUTE DIARRHOEA (WITHOUT BLOOD)⁽²¹⁾:

The objectives of treatment are to:

• Prevent dehydration, if there are no signs of dehydration;
• Treat dehydration, when it is present;
• Prevent nutritional damage, by feeding during and after diarrhoea; and
• Reduce the duration and severity of diarrhoea, and the occurrence of future episodes, by giving supplemental zinc.

TREATMENT PLAN A: Home therapy to prevent dehydration and malnutrition children with no signs of dehydration need extra fluids and salt to replace their losses of water and electrolytes due to diarrhoea. If these are not given, signs of dehydration may develop.

Mothers should be taught how to prevent dehydration at home by giving the child more fluid than usual, how to prevent malnutrition by continuing to feed the child, and why these actions are important. These steps are summarized in the four rules of Treatment Plan A:

RULE 1: Give the child more fluids than usual, to prevent dehydration.

WHAT FLUIDS TO GIVE: Wherever possible, these should include at least one fluid that normally contains salt. Plain clean water should also be given.

SUITABLE FLUIDS: Most fluids that a child normally takes can be used. It is helpful to divide suitable fluids into two groups:

Fluids that normally contain salt, such as:

• ORS solution
• Salted drinks (e.g. salted rice water or a salted yoghurt drink)
• Vegetable or chicken soup with salt.

A home-made solution containing 3g / l of table salt (one level teaspoonful) and 18g / l of common sugar (sucrose) is effective but is not generally recommended because the recipe is often forgotten, the ingredients may not be available or too little may be given.

UNSUITABLE FLUIDS: A few fluids are potentially dangerous and should be avoided during diarrhoea. Especially important are drinks sweetened with sugar, which can cause osmotic diarrhoea and hypernatraemia. Some examples are:

• Commercial carbonated beverages
• Commercial fruit juices
• Sweetened tea.

Other fluids to avoid are those with stimulant, diuretic or purgative effects, for example:

• Coffee
• Some medicinal teas or infusions.

HOW MUCH FLUID TO GIVE: The general rule is: give as much fluid as the child or adult wants until diarrhoea stops. As a guide, after each loose stool, give:

• Children under 2 years of age: 50-100 ml (a quarter to half a large cup) of fluid;
• Children aged 2 up to 10 years: 100-200 ml (a half to one large cup);
• Older children and adults: as much fluid as they want.

Rule 2: Give supplemental zinc (10 - 20 mg) to the child, every day for 10 to 14 days

Zinc can be given as a syrup or as dispersible tablets, whichever formulation is available and affordable. By giving zinc as soon as diarrhoea starts, the duration and severity of the episode as well as the risk of dehydration will be reduced. By continuing zinc supplementation for 10 to 14 days, the zinc lost during diarrhoea is fully replaced and the risk of the child having new episodes of diarrhoea in the following 2 to 3 months is reduced.

Rule 3: Continue to feed the child, to prevent malnutrition

The infant usual diet should be continued during diarrhoea and increased afterwards. Food should never be withheld and the child's usual foods should not be diluted. Breastfeeding should always be continued.

When food is given, sufficient nutrients are usually absorbed to support continued growth and weight gain. Continued feeding also speeds the recovery of normal intestinal function, including the ability to digest and absorb various nutrients. In contrast, children whose food is restricted or diluted lose weight, have diarrhoea of longer duration, and recover intestinal function more slowly.

WHAT FOODS TO GIVE: Specific recommendations are given below.

Milk:

• Infants of any age who are breastfed should be allowed to breastfeed as often and as long as they want. Infants will often breastfeed more than usual; this should be encouraged.
• Infants who are not breastfed should be given their usual milk feed (or formula) at least every three hours, if possible by cup.
• Infants below 6 months of age who take breastmilk and other foods should receive increased breastfeeding. As the child recovers and the supply of breastmilk increases, other foods should be decreased. (If fluids other than breastmilk are given, use a cup, not a bottle.) This usually takes about one week.

Other foods

If the child is at least 6 months old or is already taking soft foods, he or she should be given cereals, vegetables and other foods, in addition to milk. If the child is over 6 months and such foods are not yet being given, they should be started during the diarrhoea episode or soon after it stops.

Recommended foods should be culturally acceptable, readily available, have a high content of energy and provide adequate amounts of essential micronutrients. They should be well cooked, and mashed or ground to make them easy to digest; fermented foods are also easy to digest. Milk should be mixed with a cereal. If possible, 5-10 ml of vegetable oil should be added to each serving of cereal. Meat, fish or egg should be given, if available. Foods rich in potassium, such as bananas, green coconut water and fresh fruit juice are beneficial.

How much food and how often: Offer the child food every three or four hours (six times a day). Frequent, small feedings are tolerated better than less frequent, large ones.

After the diarrhoea stops, continue giving the same energy-rich foods and provide one more meal than usual each day for at least two weeks. If the child is malnourished, extra meals should be given until the child has regained normal weight-for-height.

RULE 4: Take the child to a health worker if there are signs of dehydration or other problems

The mother should take her child to a health worker if the child:

• starts to pass many watery stools;
• has repeated vomiting;
• becomes very thirsty;
• is eating or drinking poorly;
• develops a fever;
• has blood in the stool; or
• the child does not get better in three days.

TREATMENT PLAN B: oral rehydration therapy for children with some dehydration

Children with some dehydration should receive oral rehydration therapy (ORT) with ORS solution in a health facility following Treatment Plan B, as described below. Children with some dehydration should also receive zinc supplementation as described above.

HOW MUCH ORS SOLUTION IS NEEDED? Use Table 2 to estimate the amount of ORS solution needed for rehydration. If the child's weight is known, this should be used to determine the approximate amount of solution needed. The amount may also be estimated by multiplying the child's weight in kg times 75 ml. If the child's weight is not known, select the approximate amount according to the child's age.

Table 2: Guidelines for treating children and adults with some dehydration
Approximate amount of ORS solution to give in the first 4 hours
Agea	Less than 4 months	4 – 11 months	12 – 23 months	2 – 4 years	5 – 14 years	15 years or older
Weight	Less than 5 kg	5–7.9 kg	8-10.9 kg	11-15.9kg	16-29.9kg	30 kg or more
In ml	200-400	400-600	600-800	800-1200	1200-2200	2200-4000
a. Use the patient's age only when you do not know the weight. The approximate amount of ORS required (in ml) can also be calculated by multiplying the patient's weight in kg by 75. If the patient wants more ORS than shown, give more. Encourage the mother to continue breastfeeding her child. For infants under 6 months who are not breastfed, if using the old WHO ORS solution containing 90 mmol/L of sodium, also give 100-200ml clean water during this period. However, if using the new reduced (low) osmolarity ORS solution containing 75mmol/L of sodium, this is not necessary. NOTE: During the initial stages of therapy, while still dehydrated, adults can consume up to 750 ml per hour, if necessary, and children up to 20 ml per kg body weight per hour.

HOW TO GIVE ORS SOLUTION: A family member should be taught to prepare and give ORS solution. The solution should be given to infants and young children using a clean spoon or cup. Feeding bottles should not be used. For babies, a dropper or syringe (without the needle) can be used to put small amounts of solution into the mouth. Children under 2 years of age should be offered a teaspoonful every 1-2 minutes; older children (and adults) may take frequent sips directly from the cup.

Vomiting often occurs during the first hour or two of treatment, especially when children drink the solution too quickly, but this rarely prevents successful oral rehydration since most of the fluid is absorbed. After this time vomiting usually stops. If the child vomits, wait 5-10 minutes and then start giving ORS solution again, but more slowly (e.g. a spoonful every 2-3 minutes).

MONITORING THE PROGRESS OF ORAL REHYDRATION THERAPY: Check the child from time to time during rehydration to ensure that ORS solution is being taken satisfactorily and that signs of dehydration are not worsening. If at any time the child develops signs of severe dehydration, shift to Treatment Plan C.

After four hours, reassess the child fully. Then decide what treatment to give next:

• If signs of severe dehydration have appeared, intravenous (IV) therapy should be started following Treatment Plan C. This is very unusual, however, occurring only in children who drink ORS solution poorly and pass large watery stools frequently during the rehydration period.
• If the child still has signs indicating some dehydration, continue oral rehydration therapy by repeating Treatment Plan B. At the same time start to offer food, milk and other fluids, as described in Treatment Plan A, and continue to reassess the child frequently.
• If there are no signs of dehydration, the child should be considered fully rehydrated. When rehydration is complete:
• the skin pinch is normal;
• thirst has subsided;
• urine is passed;
• the child becomes quiet, is no longer irritable and often falls asleep.

MEETING NORMAL FLUID NEEDS: While treatment to replace the existing water and electrolyte deficit is in progress the child's normal daily fluid requirements must also be met. This can be done as follows:

• Breastfed infants: Continue to breastfeed as often and as long as the infant wants, even during oral rehydration.
• Non breastfed infants under 6 months of age: If using the old WHO ORS solution containing 90 mmol / L of sodium, also give 100-200ml clean water during this period. However, if using the new reduced (low) osmolarity ORS solution containing 75mmol / L of sodium, this is not necessary. After completing rehydration, resume full strength milk (or formula) feeds. Give water and other fluids usually taken by the infant.
• Older children and adults: Throughout rehydration and maintenance therapy, offer as much plain water to drink as they wish, in addition to ORS solution.

IF ORAL REHYDRATION THERAPY MUST BE INTERRUPTED: If the mother and child must leave before rehydration with ORS solution is completed:

• show the mother how much ORS solution to give to finish the four-hour treatment at home;
• give her enough ORS packets to complete the four hour treatment and to continue oral rehydration for two more days, as shown in Treatment Plan A;
• show her how to prepare ORS solution;
• teach her the four rules in Treatment Plan A for treating her child at home.

WHEN ORAL REHYDRATION FAILS: With the previous ORS, signs of dehydration would persist or reappear during ORT in about 5% of children. With the new reduced (low) osmolarity ORS, it is estimated that such treatment “failures” will be reduced to 3%, or less. The usual causes for these “failures” are:

• continuing rapid stool loss (more than 15-20 ml / kg / hour), as occurs in some children with cholera;
• insufficient intake of ORS solution owing to fatigue or lethargy;
• frequent, severe vomiting.

Such children should be given ORS solution by nasogastric (NG) tube or Ringer's Lactate Solution intravenously (IV) (75 ml / kg in four hours), usually in hospital. After confirming that the signs of dehydration have improved, it is usually possible to resume ORT successfully.

Rarely, ORT should not be given. This is true for children with:

• abdominal distension with paralytic ileus, which may be caused by opiate drugs (e.g. codeine, loperamide) and hypokalaemia;
• glucose malabsorption, indicated by a marked increase in stool output when ORS solution is given, failure of the signs of dehydration to improve and a large amount of glucose in the stool when ORS solution is given.

In these situations, rehydration should be given IV until diarrhoea subsides; NG therapy should not be used.

GIVING ZINC: Begin to give supplemental zinc, as in Treatment Plan A, as soon the child is able to eat following the initial four-hour rehydration period.

GIVING FOOD: Except for breastmilk, food should not be given during the initial four-hour rehydration period. However, children continued on Treatment Plan B longer than four hours should be given some food every 3-4 hours as described in Treatment Plan A. All children older than 6 months should be given some food before being sent home. This helps to emphasize to mothers the importance of continued feeding during diarrhoea.

TREATMENT PLAN C: for patients with severe dehydration.

GUIDELINES FOR INTRAVENOUS REHYDRATION: The preferred treatment for children with severe dehydration is rapid intravenous rehydration, following Treatment Plan C. If possible, the child should be admitted to hospital. Guidelines for intravenous rehydration are given in Table 3.

Children who can drink, even poorly, should be given ORS solution by mouth until the IV drip is running. In addition, all children should start to receive some ORS solution (about 5 ml / kg / h) when they can drink without difficulty, which is usually within 3-4 hours (for infants) or 1-2 hours (for older patients). This provides additional base and potassium, which may not be adequately supplied by the IV fluid.

Table 3: Guidelines for intravenous treatment of children and adults with severe dehydration Start IV fluids immediately. If the patient can drink, give ORS by mouth until the drip is set up. Give 100 ml / kg Ringer's Lactate Solutiona divided as follows:
Age	First give 30 ml/kg in:	Then give 70 ml/kg in:
Infants (under 12 months)	1 hourb	5 hours
Older	30 minutesb	2½ hours
Reassess the patient every 1-2 hours. If hydration is not improving, give the IV drip more rapidly. After six hours (infants) or three hours (older patients), evaluate the patient using the assessment chart. Then choose the appropriate Treatment Plan (A, B or C) to continue treatment. a If Ringer's Lactate Solution is not available, normal saline may be used. b Repeat once if radial pulse is still very weak or not detectable.

MONITORING THE PROGRESS OF INTRAVENOUS REHYDRATION: Patients should be reassessed every 15-30 minutes until a strong radial pulse is present. Thereafter, they should be reassessed at least every hour to confirm that hydration is improving. If it is not, the IV drip should be given more rapidly.

Look and feel for all the signs of dehydration:

• If signs of severe dehydration are still present, repeat the IV fluid infusion as outlined in Treatment Plan C. This is very unusual, however, occurring only in children who pass large watery stools frequently during the rehydration period.
• If the child is improving (able to drink) but still shows signs of some dehydration, discontinue the IV infusion and give ORS solution for four hours, as specified in Treatment Plan B.
• If there are no signs of dehydration, follow Treatment Plan A. If possible, observe the child for at least six hours before discharge while the mother gives the child ORS solution, to confirm that she is able to maintain the child's hydration. Remember that the child will require therapy with ORS solution until diarrhoea stops.

WHAT TO DO IF INTRAVENOUS THERAPY IS NOT AVAILABLE: If IV therapy is not available at the facility, but can be given nearby (i.e. within 30 minutes), send the child immediately for IV treatment. If the child can drink, give the mother some ORS solution and show her how to give it to her child during the journey.

If IV therapy is not available nearby, health workers who have been trained can give ORS solution by NG tube, at a rate of 20 ml / kg body weight per hour for six hours (total of 120 ml / kg body weight). If the abdomen becomes swollen, ORS solution should be given more slowly until it becomes less distended.

If NG treatment is not possible but the child can drink, ORS solution should be given by mouth at a rate of 20 ml / kg body weight per hour for six hours (total of 120 ml / kg body weight). If this rate is too fast, the child may vomit repeatedly. In that case, give ORS solution more slowly until vomiting subsides.

Children receiving NG or oral therapy should be reassessed at least every hour. If the signs of dehydration do not improve after three hours, the child must be taken immediately to the nearest facility where IV therapy is available. Otherwise, if rehydration is progressing satisfactorily, the child should be reassessed after six hours and a decision on further treatment made as described above for those given IV therapy.

MALNOURISHED CHILDREN: Intravenous fluids should be used only in patients with overt shock, and a specialized approach to the composition and administration of ORS is required.^(20,21) The WHO recommends the use of reduced osmolality ORS in malnourished children. All patients with severe malnutrition and diarrhea should be started on empiric broad spectrum antibiotics immediately, as well as appropriate nutritional therapy.^(20,21)

NUTRITION: The goal of nutritional management for patients without malnutrition is to encourage sufficient feeding both during and after the diarrheal illness episode to prevent development of malnutrition and chronic enteropathy.

Infants with diarrhea should be encouraged to breastfeed as much as possible.⁽²¹⁾ Infants that are not breastfed should be encouraged to continue to take undiluted formula at least every three hours, in addition to ORS. For infants with dehydration, this should start once rehydration is completed.

Children with diarrhea should be encouraged to take solid foods immediately after initial dehydration is corrected; delaying the initiation of a nutrient rich diet may increase the risk of malnutrition.

As long as diarrhea persists, foods high in energy content and micronutrients should be offered at frequent intervals (at least six meals a day). After diarrhea resolves, at least one extra meal per day should be continued for a minimum of two weeks, or until the patient regains normal weight-for-height.⁽²¹⁾

VITAMINS AND MINERALS:

ZINC: Several studies have demonstrated that zinc supplementation reduces the severity and duration of diarrhea and reduces the incidence of subsequent episodes of diarrhea for several months.^(22-24) Based on these studies, the WHO recommends zinc for children under 5 years of age with diarrhea (10 mg / day for children under 6 months and 20 mg / day for children 6 months to 5 years, each for 10 days).

VITAMIN A: Children with diarrhea in resource-limited countries are at high risk of vitamin A deficiency and should receive high dose supplementation with vitamin A. Patients with signs of xerophthalmia, severe malnutrition, or a history of measles should receive a three dose series of repeated treatments for vitamin A deficiency.⁽¹⁵⁾

ANTIBIOTICS:

Antibiotics are not indicated for most children with acute watery diarrhea; suspected cholera is an important exception in which antibiotic therapy is useful.

OTHER THERAPIES: The mainstays of treatment for children with diarrhea in resource-limited countries are correction of fluid and electrolyte losses, appropriate nutritional care, and treatment of associated comorbid conditions. No additional therapies have well established benefits and some are potentially harmful. Children with acute diarrhea should NOT receive antimotility agents or antiemetics. Antimotility agents (loperamide, diphenoxylate-atropine, and tincture of opium) prolong some bacterial infections and may cause fatal paralytic ileus in children.⁽²⁵⁾ Antiemetics (chlorpromazine, prochlorperazine, promethazine, and metoclopramide) have sedating effects that can interfere with rehydration and may cause extrapyramidal reactions and respiratory depression.⁽²¹⁾

INVASIVE DIARRHEA:

Treatment consists of invasive diarrhea requires correction of fluid and electrolyte losses, appropriate nutritional care, and treatment of the underlying cause of illness. The management of fluids and nutrition is as described in the preceding sections.

Empiric antibiotic therapy for acute bloody diarrhea should be targeted against Shigella species. Antimicrobial treatment of Shigella gastroenteritis reduces the duration of fever and diarrhea, decreases the duration of bacterial shedding, and may reduce the risk of life threatening complications of infection such as bacteremia.⁽²⁶⁾

For children with bloody diarrhea that does not remit within two days of starting empiric antibiotics for shigellosis, antibiotic-resistant infection or an alternative infectious etiology should be considered. Amebic dysentery due to the intestinal parasite E. histolytica may be clinically indistinguishable from shigellosis and does not respond to anti-Shigella therapy. Direct stool microscopy can be used for presumptive diagnosis. Metronidazole (35 to 50 mg / kg per day in three divided doses for 7 to 10 days in children to a maximum of 750 mg PO three times daily) is a standard treatment regimen with a cure rate of approximately 90 percent.⁽²⁷⁾

PROBIOTICS:

Recently, some strains of probiotics (defined as live microorganisms that when ingested in adequate doses, provide a benefit to the host) have been found to be effective as an adjunct when treating children with acute diarrhea. Multiple systematic reviews have demonstrated a modest reduction in the duration of infectious diarrhea with the use of probiotics, although there was heterogeneity among studies.^(28-34)

Data to support the specific type, dose, or duration of probiotic, and the mechanism of protection from specific etiologic agents are limited. It is also unclear whether probiotics reduce important complications of diarrheal illness such as dehydration and malnutrition.

IMMUNIZATIONS:

The WHO Strategic Advisory Group of Experts has recommended that rotavirus vaccine for infants be included in all national immunization programs, and strongly recommended the introduction of this vaccine in countries where diarrheal deaths account for ≥10 percent of mortality among children aged <5 years.⁽³⁵⁾

The WHO recommends the inclusion of oral cholera vaccines in endemic areas, and oral cholera vaccines are increasingly being utilized, through the global cholera vaccine stockpile, as part of an integrated control program in areas experiencing or at risk for cholera outbreaks.

GOAL OF THERAPY:

The goals of therapy are to reduce subsequent episodes of diarrhea, malnutrition, and delays in physical and mental development.

GUIDELINES:

To view, “American family physician - Gastroenteritis and Diarrhea in Children” guidelines, please click on below link:

http://www.aafp.org/afp/topicModules/viewTopicModule.htm?topicModuleId=9#0

To view, “European Society for Pediatric Gastroenterology, Hepatology, and Nutrition / European Society for Pediatric Infectious Diseases Evidence-Based Guidelines for the Management of Acute Gastroenteritis in Children in Europe: Update 2014”, please click on below link:

http://www.espghan.org/fileadmin/user_upload/guidelines_pdf/Guidelines_2404/European_Society_for_Pediatric_Gastroenterology_.26.pdf

To view, World Gastroenterology Organisation Global Guidelines, Acute Diarrhea in Adults and Children: A Global Perspective”, please click on below link:

http://www.worldgastroenterology.org/guidelines/global-guidelines/acute-diarrhea/acute-diarrhea-english

To view, “Diarrhoea and vomiting caused by gastroenteritis in under 5s: diagnosis and management – National Institure for Health and Care Excellence (NICE)”, please click on below link:

https://www.nice.org.uk/guidance/CG84?UNLID=51453916120171280358

To view, “The treatment of diarrhoea - A manual for physicians and other senior health workers from World Health Organization (WHO), please click on below link:

http://www.who.int/maternal_child_adolescent/documents/9241593180/en/

CONSULTATION AND COUNCELLING:

Following consultation should be carried out with the patient / patient’s relative.

Most diarrhea cases clear up on their own within a few days. To help you cope with your signs and symptoms until the diarrhea goes away, try to:

• Drink plenty of clear liquids,including water, broths and juices. Avoid caffeine and alcohol.
• Add semisolid and low-fiber foods graduallyas your bowel movements return to normal. Try toast, eggs, rice or chicken.
• Avoid certain foodssuch as dairy products, fatty foods, high-fiber foods or highly seasoned foods for a few days.

PREVENTION

• Exclusive breastfeeding until age six months, and continued breastfeeding with complementary foods until two years of age. Complementary feeding may be considered in younger infants if growth is inadequate.
• The consumption of safe food and water. If available, water brought to a rolling boil for at least five minutes is optimal for preparing food and drinks for young children.
• Handwashing after defecating, disposing of a child's stool, and before preparing meals.
• The use of latrines; these should be located more than 10 meters and downhill from drinking water sources.

REFERENCES:

1. http://www.who.int/mediacentre/factsheets/fs330/en/ Accessed on 9-Mar-2017
2. Pakistan Strategic Country Environment Assessment – World Bank 2006
3. UNICEF_Annual_Report_2013_-_Version_11.1 (https://www.unicef.org/pakistan/FINAL_UNICEF_Annual_Report_2013_-_Version_11.1.pdf Accessed on 9-Mar-17)
4. http://floods2010.pakresponse.info/Nutrition/surveys/MICS_Punjab_2007- 08.pdf Accessed on 9-Mar-17
5. King CK, Glass R, Bresee JS, Duggan C,. Managing acute gastroenteritis among children: oral rehydration, maintenance, and nutritional therapy.MMWR Recomm Rep. 2003 Nov 21. 52(RR-16):1-16
6. Field M. Intestinal ion transport and the pathophysiology of diarrhea. J Clin Invest 2003; 111:931.
7. Acheson DWK, Keusch GT. Shigella and enteroinvasive Escherichia coli. In: Infections of the Gastrointestinal Tract, Blaser MJ, Smith PD, Ravdin JI, et al (Eds), Raven, New York 1995. p.763.
8. Belongia EA, Osterholm MT, Soler JT, et al. Transmission of Escherichia coli O157:H7 infection in Minnesota child day-care facilities. JAMA 1993; 269:883.
9. Kaper JB, Nataro JP, Mobley HL. Pathogenic Escherichia coli. Nat Rev Microbiol 2004; 2:123.
10. http://almashriq.hiof.no/lebanon/600/610/614/solar-water/unesco/06-07.html
11. Guarino A, De Marco G, for the Italian National Network for Pediatric Intestinal Failure. Natural history of intestinal failure, investigated through a national network-based approach. J Pediatr Gastroenterol Nutr. 2003 Aug;37(2):136-41.
12. Gorelick MH, Shaw KN, Murphy KO. Validity and reliability of clinical signs in the diagnosis of dehydration in children. Pediatrics 1997; 99:E6.
13. Duggan C, Refat M, Hashem M, et al. How valid are clinical signs of dehydration in infants? J Pediatr Gastroenterol Nutr 1996; 22:56.
14. Steiner MJ, DeWalt DA, Byerley JS. Is this child dehydrated? JAMA 2004; 291:2746.
15. World Health Organization. The management of acute respiratory infections in children. In: Practical guidelines for outpatient care. World Health Organization, Geneva, 1995.
16. Chisti MJ, Ahmed T, Faruque AS, Abdus Salam M. Clinical and laboratory features of radiologic pneumonia in severely malnourished infants attending an urban diarrhea treatment center in Bangladesh. Pediatr Infect Dis J 2010; 29:174.
17. Chisti MJ, Tebruegge M, La Vincente S, et al. Pneumonia in severely malnourished children in developing countries - mortality risk, aetiology and validity of WHO clinical signs: a systematic review. Trop Med Int Health 2009; 14:1173.
18. Chisti MJ, Huq S, Das SK, et al. Predictors of severe illness in children under age five with concomitant infection with pneumonia and diarrhea at a large hospital in Dhaka, Bangladesh. Southeast Asian J Trop Med Public Health 2008; 39:719.
19. Bennish ML, Azad AK, Yousefzadeh D. Intestinal obstruction during shigellosis: incidence, clinical features, risk factors, and outcome. Gastroenterology 1991; 101:626.
20. Management of severe malnutrition: a manual for physicians and other senior health workers, WHO, Geneva 1999 www.who.int/nutrition/publications/malnutrition/en/index.html
21. World Health Organization. The treatment of diarrhoea, a manual for physicians and other senior health workers. -- 4th revision. WHO/FCH/CAH/05.1. Geneva: World Health Organization, 2005. http://whqlibdoc.who.int/publications/2005/9241593180.pdf
22. Lazzerini M, Ronfani L. Oral zinc for treating diarrhoea in children. Cochrane Database Syst Rev 2012; :CD005436.
23. 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.
24. Bhandari N, Mazumder S, Taneja S, et al. Effectiveness of zinc supplementation plus oral rehydration salts compared with oral rehydration salts alone as a treatment for acute diarrhea in a primary care setting: a cluster randomized trial. Pediatrics 2008; 121:e1279.
25. Li ST, Grossman DC, Cummings P. Loperamide therapy for acute diarrhea in children: systematic review and meta-analysis. PLoS Med 2007; 4:e98.
26. Christopher PR, David KV, John SM, Sankarapandian V. Antibiotic therapy for Shigella dysentery. Cochrane Database Syst Rev 2009; :CD006784.
27. Bercu TE, Petri WA, Behm JW. Amebic colitis: new insights into pathogenesis and treatment. Curr Gastroenterol Rep 2007; 9:429.
28. Van Niel CW, Feudtner C, Garrison MM, Christakis DA. Lactobacillus therapy for acute infectious diarrhea in children: a meta-analysis. Pediatrics 2002; 109:678.
29. McFarland LV. Meta-analysis of probiotics for the prevention of traveler's diarrhea. Travel Med Infect Dis 2007; 5:97.
30. Szajewska H, Skórka A, Ruszczyński M, Gieruszczak-Białek D. Meta-analysis: Lactobacillus GG for treating acute diarrhoea in children. Aliment Pharmacol Ther 2007; 25:871.
31. Britton RA, Versalovic J. Probiotics and gastrointestinal infections. Interdiscip Perspect Infect Dis 2008; 2008:290769.
32. Szajewska H, Skórka A. Saccharomyces boulardii for treating acute gastroenteritis in children: updated meta-analysis of randomized controlled trials. Aliment Pharmacol Ther 2009; 30:960.
33. Allen SJ, Martinez EG, Gregorio GV, Dans LF. Probiotics for treating acute infectious diarrhoea. Cochrane Database Syst Rev 2010; :CD003048.
34. Bernaola Aponte G, Bada Mancilla CA, Carreazo NY, Rojas Galarza RA. Probiotics for treating persistent diarrhoea in children. Cochrane Database Syst Rev 2013; :CD007401.
35. Meeting of the immunization Strategic Advisory Group of Experts, April 2009--conclusions and recommendations. Wkly Epidemiol Rec 2009; 84:220.