DIARRHEAL DISEASES

Global Burden of Diarrhea and Epidemiological Trends

Diarrheal illnesses in young children are among the leading causes of morbidity and mortality in developing countries. Diarrhea is an important cause of morbidity in developed countries as well. In developing countries, children younger than 5 years old suffer 3–10 episodes of diarrhea per year, whereas in developed countries young children have on average 1 or 2 diarrheal episodes per year. The advent of oral rehydration therapy (ORT) and its use in the past three decades have dramatically reduced the case fatality rate for diarrhea. However, globally the estimated 3 billion annual episodes of diarrhea account for approximately 2 million deaths in children younger than 5 years old. The majority of diarrhea-related mortality occurs in developing countries and the highest rates of diarrhea occur among infants with malnutrition. The case fatality rate is highest among children 6 months to 1 year old. The primary reason is that for most children this is the period when the immune system is not yet fully matured and the maternal antibodies are reduced. In addition, they may receive contaminated foods to complement breast-feeding, and they begin to crawl, potentially to areas where they may have direct contact with human or animal feces.

Although dehydration is the most direct effect of diarrhea, there are many adverse and potentially fatal nutritional consequences when proper nutritional management is not followed. This article provides an overview of the epidemiology of diarrheal diseases, including the interaction of diarrhea and malnutrition, and discusses the treatment of diarrhea, including fluid therapy and dietary management to minimize the nutritional cost of diarrhea.

Diarrhea–Malnutrition Interaction

Diarrheal illnesses are more common, last longer, are clinically more severe, and are more likely to have a fatal outcome for impoverished children in less developed countries because of a complex interaction between infection, protein-energy malnutrition, and micronutrient deficiencies. Diarrhea and malnutrition have a bidirectional relationship in which malnutrition increases the incidence and duration of diarrhea and, conversely, diarrhea exerts a negative effect on nutritional status. Malnourished children have defects in cell-mediated immune functions and a decrease in IgA-containing cells in the jejunal mucosa. Malnutrition produces morphological and functional changes in virtually all organs. Changes in the intestine include thinning of the gut epithelium, marked flattening and broadening of villi, extensive infiltration of the lamina propria, and diminished secretion of gastric acid. These changes lead to an increased risk of diarrhea. The risk of developing diarrhea may be predicted by a child's ability to respond to skin test antigens. This effect of impaired cellular immunity is independent of age and nutritional status. Studies have shown that patients with a variety of viral and bacterial infections, such as measles, influenza, tuberculosis, and streptococcal infections, develop impaired cell-mediated immunity (anergy). Anergy or reduced responsiveness may also be associated with single nutrient deficiency, such as deficiency of vitamin A, zinc, pyridoxine, folic acid, and iron. Therefore, it may be possible that in an otherwise healthy child, infection or micronutrient deficiencies induce immunodeficiency may increase susceptibility to diarrhea and other infections and lead to a vicious cycle of repeated infections, anergy, and deteriorating nutritional status.

Diarrheal diseases have generally been noted to have an adverse effect on growth of underprivileged children in developing countries. Community-based prospective studies in developing countries have consistently demonstrated a significant negative effect of diarrhea on short-term weight gain, but studies on the effect on short-term height gain are less consistent. On the contrary, some investigators have concluded that the effect of diarrhea on growth is transient and that efforts to control diarrhea are unlikely to improve children's nutritional status. One possible explanation for the discrepant findings is the heterogeneity of diarrheal illnesses. Most studies that have examined the effect of diarrhea on growth have considered diarrhea as a single entity. Studies that have examined the effect of diarrhea on growth by type of diarrheal illness have suggested that certain etiological (e.g., Shigella spp.) and clinical-type (dysentery) illnesses are associated with significant growth retardation. It has been estimated that diarrheal illnesses account for 10–80% of growth retardation in the first few years of life, with the magnitude of effect possibly modified by other factors, such as etiology and clinical type, the source and adequacy of dietary intake, treatment and feeding practices during and following illness, and the opportunity for catch-up growth after illness. A cohort study conducted in Bangladesh observed that dysentery had the most deleterious consequences on both ponderal and linear growth, although other types of diarrhea showed a similar but relatively less pronounced negative effect on growth. Losses of approximately 0.5 kg in annual weight gain and 1.25 cm in annual height gain were associated with dysentery in children < 5 years old in this population.

Understanding the mechanisms of diarrhea-induced undernutrition and appropriate treatment of diarrhea is important for the immediate illness and also for the long-term well-being of children. Approximately 10% of diarrheal episodes result in persistent diarrhea lasting more than 2 weeks. These infants need specialized treatment in addition to rehydration therapy, such as antibiotics for concurrent infections, micronutrients, and careful dietary management. In many settings, up to 50% of diarrhea-associated deaths occur in children with malnutrition-associated persistent diarrhea.

Clinical Types and Etiology of Diarrhea

Since nutritional costs of diarrhea vary by etiology and clinical type, a discussion of different types of diarrhea is pertinent. Diarrheal episodes can be classified based on clinical presentation as inflammatory (dysentery) and noninflammatory (nondysentery) diarrhea. Therefore, the clinical presentation of diarrheal illnesses may suggest a causative diagnosis. Diarrheal episodes can also be classified based on duration as acute (< 14 days) and persistent (≥14 days) diarrhea. The diarrhea is generally due to either infectious or noninfectious causes. This article focuses on infectious diarrhea. Pathogens that cause infectious diarrhea include bacteria, viruses, and parasites (Table 1).

Table 1.

Infectious causes of diarrhea

Bacterial

Shigella species

Salmonella

Campylobacter jejuni

Enteroadherent Escherichia coli

Enteroinvasive Escherichia coli

Enterohemorrhagic Escherichia coli

Yersinia enterocolitica

Staphylococcus aureas

Bacillius cereus

Vibrio cholerae non-O group 1

Vibrio parahaemolyticus

Listeria monocytogenes

Aeromonas hydrophilia

Plesliomonas shigelloides

Viruses

Rotavirus

Norovirus

Enteric adenovirus

Calcivirus

Astrovirus

Coronavirus

Cytomegalovirus

Parasites

Giardia lamblia

Entamoeba histolytica

Cryptosporidium

Cyclospora

Isospora belli

Microsporidia

Strongyloides

Food poisoning

Staphylococcus aureus

Clostridium perfringens

Bacillus cereus

Drugs, especially antibiotic induced

Clostridium difficile

Most diarrheal episodes are acute. Occasionally, they become prolonged, leading to a vicious cycle of malabsorption, malnutrition, and failure to thrive. Noninfectious diarrhea tends to be persistent because it is often due to a chronic health problem. However, most persistent diarrhea is due to infection or is a sequeale of infection. Infections can lead to persistent diarrhea in the following situations: (i) Some pathogens cause chronic symptoms, usually parasites but sometimes bacteria; (ii) immunosuppressed individuals, such as those with human immunodeficiency virus (HIV) infection, cannot effectively clear pathogens and can develop persistent diarrhea; and (iii) at times the infection clears, but people develop chronic symptoms, such as irritable bowel syndrome, with diarrhea. If the diarrhea is persistent, it can cause dehydration, malnutrition, and systemic infections. Diarrhea in combination with a severe case of malnutrition (e.g., marasmus and kwashiorkor) is very dangerous and can lead to systematic infections and death. Although many different mechanisms may contribute to persistent diarrhea, the result is a similar pathophysiologic syndrome of mucosal atrophy, inflammation, and malabsoption. Therapeutic efforts should concentrate on nutritional rehabilitation.

Factors Influencing Nutritional Decline in Diarrhea

Factors that influence a nutritional decline during a period of diarrhea include reduced food intake, diminished nutrient absorption due to malabsorption of macro- and micronutrients and shorter intestinal transit time, direct loss of protein and other nutrients, and an increase in the body's demand for nutrients. In addition, diarrhea of infectious origins causes cytokine-induced malnutrition, which results from the action of proinflammatory cytokines such as tumor necrosis factor and interleukin-1, -6, and -8.

Food Intake during Diarrhea

Food intake during diarrhea is often reduced due to poor appetite (anorexia), vomiting, deliberate withholding of food, and inappropriate dietary supplementation with diluted food items. Diarrhea can also be associated with fever. Both fever and anorexia have clear effects on the nutritional status of the host. An increase in body temperature of 1 °C causes an increase in the basal metabolic rate of 12–23%. Although the reason for anorexia is not clear, its effect can be important. In a controlled study in Bangladesh, 41 hospitalized children with acute diarrhea consumed only about half of the total calories consumed by healthy children despite an educational intervention.

Malabsorption of Nutrients

Malabsorption in diarrheal illness may result from the epithelial destruction by the pathogen. Diminished nutrient absorption often begins during acute diarrhea. At this time, the body is less able to absorb needed macronutrients, including fats and proteins, as well as some carbohydrates. This is most severe in undernourished children who suffer from persistent diarrhea due to damage to the gut epithelium. When the gut is damaged, food is not properly digested or absorbed. The causes of insufficient nutrient absorption include diminished concentration of bile acids, which are used for fat absorption; damaged epithelial cells, which provide the absorptive surface on the bowel; and a deficiency of disaccharides due to damaged microvilli, which normally produce the needed enzymes. In symptomatic rotavirus infection, the most common cause of acute severe diarheal illness worldwide, there is a 42% decrease in the absorption of nitrogen and fat, a 48% decrease in absorption of carbohydrates, and a 55% decrease in the total carbohydrate absorption. Malabsoption is more severe in both ETEC and shigella diarrhea. In shigellosis, loss of protein and vitamin A is sizeable. Giardiasis leads to malabsorption of vitamin A. A large amount of zinc is lost in diarrhea, usually resulting in a negative net zinc balance during the illness.

Increased Demand for Nutrients

During episodes of diarrhea, the body requires more nutrients than normal. This is due to the need to repair the damage to the gut epithelium, the increased metabolic demand on the body made by a fever, and, during dysentery, the need to replace serum protein lost by exudation through the damaged intestinal mucosa.

Management of Diarrhea

An invariable accompaniment of diarrhea, particularly persistent diarrhea, is protein-energy malnutrition. However, dehydration is the most immediate complication of diarrhea. Clinical management of acute diarrhea includes four major components: (i) replacement of fluid and electrolyte losses, (ii) zinc therapy, (iii) antimicrobial therapy when indicated, and (iv) continued feeding to supply a sufficient quantity of nutrients to meet both the patient's usual maintenance requirement and the increased needs imposed by infection and malabsoption.

Fluid Therapy

The majority of the diarrhea-associated deaths result from dehydration. Parents should be encouraged to increase fluid intake as soon as diarrhea begins and to give oral rehydration solution if available. Children presenting with diarrhea should be assessed for dehydration. Thirst is an early sign of dehydration in a child. Other signs are mucosal dryness (e.g., dry mouth), sunken eyes, and loss of skin turgor. The coexistence of fever or vomiting exacerbates dehydration. The World Health Organization (WHO) guidelines classify dehydration into two categories—some dehydration and severe dehydration. Weight loss is the main clinical index of degree of dehydration. A vast majority of children with diarrhea present with some dehydration or no clinical signs of dehydration. The cornerstone of treatment for these children is oral rehydration solution (ORS) containing glucose or sucrose and electrolytes. ORS is effective but it must start as soon as diarrhea starts. In children with some dehydration, approximately 100 ml/kg of body weight of ORS should be given within 4 h. Ongoing stool losses should be replaced with ORS. Rehydration and maintenance of hydration in a vomiting child is feasible using ORS by giving small amounts frequently. Severe dehydration is a medical emergency that requires immediate intravenous fluid replacement, and children should preferably be hospitalized. Patients presenting with severe dehydration should receive 40 ml/kg body weight of Ringers lactate or similar intravenous solutions over a 4-h period. ORS should be given as soon as the child is able to drink.

Regardless of etiology, watery diarrhea requires fluid and electrolyte replacement. For more than three decades, an ORS containing 90 mmol/l of sodium and 111 mmol/l of glucose was used throughout the world. This solution has been credited with saving millions of lives. WHO and UNICEF have recommended the use of a new reduced osmolarity ORS formulation consisting of 75 mmol/l of sodium and 75 mmol/l of glucose and total osmolarity of 245 mOSm/l. This recommendation was made on the basis of studies that have demonstrated that the reduced osmolarity ORS was at least as efficacious as the standard ORS containing 90 mmol/l of sodium and an osmolarity of 311/l. In addition, in a meta-analysis, the reduced osmolarity ORS was shown to decrease the need for unscheduled intravenous therapy by 33%, the stool output was reduced by 20%, and the incidence of vomiting was reduced by 30%. However, there is concern that this low osmolar ORS may lead to asymptomatic and symptomatic hyponatremia in adults with severe diarrhea. This issue needs to be evaluated in large-scale effectiveness trials. Despite the proven efficacy of ORS, only approximately 20% of children receive appropriate ORS therapy during diarrheal episodes. The barriers to use of ORS include lack of knowledge of the importance of rehydration therapy, lack of access to ORS, and the perception that ORS is not a medicine since it does not stop the diarrhea.

The management of a child with persistent diarrhea is often difficult due to other related heath issues. These children are more likely to be severely undernourished due to micronutrient and protein-energy malnutrition as well as more prone to systematic infections. Due to the systematic infections, appropriate antibiotic therapy is needed.

Dietary Management of Diarrhea, Including Persistent Diarrhea

Data suggest that continued feeding during diarrhea is generally well tolerated and it minimizes the nutritional cost associated with diarrhea. A child should receive the same type of food during an episode of diarrhea as when the child is healthy. Feeding is usually tolerated, with the occasional exception of lactose intolerance. A small subgroup of children exclusively receiving nonhuman milk may have a higher rate of complications. These children should be closely supervised and provided with alternatives if needed. Full feedings will help to minimize growth faltering and a decline in nutritional status. Growth faltering may still occur, especially in severely undernourished children, due to poor nutrient absorption.

Importance of Continued Breast Feeding

Breast feeding should be continued for as long as the child can tolerate it during episodes of acute diarrhea as well as during persistent diarrhea. It is normally well tolerated during such episodes and has been shown to reduce stool output and decrease the duration of the illness compared to those of non-breast-fed children.

Milk Intolerance: Lactose Intolerance

The majority of children can tolerate lactose during a diarrheal episode. A small proportion of children with diarrhea may not be able to digest lactose and are therefore not tolerant of milk- and lactose-containing formulas. This is more likely to occur among young children who only receive animal milk or formula in their diet and who have persistent diarrhea, and it rarely occurs in children on a diet of breast milk. In a lactose-intolerant child, milk- and lactose-containing formulas result in a significant increase in stool output. Stool output reduces dramatically when the milk- or lactose-containing formula is stopped. The warning signs of lactose intolerance include deterioration of the child's clinical condition, signs of dehydration, and an increase in the stool volume when milk feedings are given. However, only when the child is not gaining weight, eating less, and not fully alert is this a real cause for concern. This condition can be managed by continuing breast feeding. If the child is not yet in the weaning period but takes animal milk, yogurt or diluted milk (equal water and milk) or soy milk can be used as a substitute given in small feedings. The child should be taken to a health care provider if the condition does not improve in 2 days.

If the child eats soft or solid foods, the lactose in the diet should be substituted in the same manner as for the infant (with diluted milk or soy milk) but mixed with cooked cereals and vegetables. If this does not improve the condition of the child, all animal milk should be excluded from the diet, and protein- and energy-rich foods such as finely ground chicken should be given. The treatment should be continued for a few days after the cessation of the diarrhea, when the milk is slowly replaced in the diet.

Soft or Solid Food, Energy Density of Diet, and Protein and Energy Requirements

A child's diet during the period of diarrhea should not be drastically different from his or her normal healthy diet. Therefore, for children who are currently breast-feeding, they should continue to do so, and for children who are in the weaning period and have a mixed diet, they should continue to have a mixed diet of soft or solid food. If the child on a mixed diet is dehydrated, his or her soft and solid foods should be temporarily stopped for a period of approximately 4 h when he or she rehydrates. However, it should then be resumed. For children who are in the weaning stages, WHO recommends small, frequent feedings (six or more times a day) to increase nutrient absorption. The type of food should be energy rich, low in bulk, locally available, and nutritious. The diet should contain complementary protein sources and easily digestible fats, and complex carbohydrates should be avoided. All the foods should be well cooked. Easily digestible staple foods that can be easily mashed include rice, corn, potatoes, and noodles. These staple foods should be mixed with vegetables as well as sources of protein if possible. It is also important to ensure adequate rehydration. In addition, the consumption of fresh fruit juices and mashed bananas is highly encouraged because they provide a good source of potassium.

Feeding during the Convalescent Period

The convalescent period is the recovery period for the body during which the child's diarrhea has stopped but the body has not yet fully recovered to its initial condition. During the first few weeks, the child's appetite will be returning and the child may consume up to twice as much as usual. This is a necessary part of the process because even if the child was fully fed during diarrhea, he or she most likely did not absorb sufficient nutrients. During this time, the child's nutritional state should return to at least the level before the child became ill. The desired energy intake ranges from 100 to 160 J/kg per day, which is achieved with a high-energy, low-bulk, and low-viscosity diet. This is needed for a catch-up growth period and rapid nutritional recovery.

Supplementation with Micronutrients

ORT reduces mortality from dehydrating diarrhea, but it does not decrease the duration of episodes or their consequences, such as malnutrition. In addition, adherence to recommendations regarding ORT in children is poor because caregivers want to reduce the duration of illness. This often leads to use of antibiotics and other treatment of no proven value. In addition, there are indications that knowledge and use of appropriate home therapies, including ORT, to manage diarrhea successfully may be declining in some countries. The limitations of ORT and continued high diarrhoeal morbidity, mortality, and associated malnutrition led to a search for adjunct therapies. Zinc and vitamin A are essential to repair the intestinal mucosa and boost immunological responses. These supplements should be given during periods of diarrhea.

Zinc

Based on the results of a large number of randomized controlled trials that have demonstrated the therapeutic benefits of zinc supplementation during diarrhea, WHO and UNICEF have recommended the use of zinc supplementation at a dose of approximately 2 RDAs per day (10–20 mg) for 10–14 days. This strategy has the advantage of having a good delivery mechanism (i.e., during the delivery of ORS packets). The effectiveness of different delivery strategies is being evaluated in large-scale trials.

A study from India evaluated the efficacy of zinc-fortified ORS and reported that zinc–ORS was moderately efficacious in reducing the severity of acute diarrhea. If these results are confirmed by other studies, this strategy has the advantage of reducing the need to deliver the zinc supplementation separate from the ORS packets. However, it will probably result in increased cost of ORS production and not all countries will be able to rapidly scale up the production of zinc–ORS in the near future. Additional potential disadvantages of this strategy are that coverage with ORS is low, ORS is usually needed only for 2 or 3 days, and the volume of ORS taken is generally low. Therefore, it will be difficult to ensure adequate zinc intake.

Vitamin A

The body's ability to absorb vitamin A during diarrhea is reduced, which may lead to acute vitamin A deficiency. Repeated episodes may lead to blindness and signs of xerophthalmia. If these are recognized, 200 000 units of vitamin A should be orally administered to children (100 000 units for infants). There should be two subsequent doses, one the following day and another in 4 weeks. In areas where vitamin A deficiency is a problem, any foods that are rich in carotene should be administered (including dark leafy vegetables and yellow or orange fruits and vegetables). Vitamin A deficiency is most common among severely undernourished children and among children who have recently recovered from the measles.

Medications

Antimicrobials and antiparasitics should not be regularly used. Most episodes do not benefit from these treatments, with the following exceptions: in suspect cases of cholera, in cases of persistent diarrhea when cysts or trophozoites of Giardia are identified in the feces, and antibiotics that are effective for Shigella are only used for cases of dysentery (blood in the stool).

Management of Diarrhea in Children with Severe Malnutrition

Children who are severely undernourished and have diarrhea often have other infections. Infections can cause hypothermia as opposed to fever. An appropriate antibiotic should be give if an infection is identified.

Assessment of Dehydration in a Severely Malnourished Child

Children who are severely undernourished have different, unreliable signs and symptoms to assess the status of their hydration. For example, children with marasmus have poor skin elasticity even though they are not dehydrated, and sunken eyes are also not a reliable sign. Irritability in these children may be a sign of systemic infection rather than dehydration. The skin of children with kwashiorkor, on the other hand, may appear to be normal even if they are dehydrated. These children generally have apathetic attitudes. Undernourished children do not readily cry, so determining the absence of tears is also a challenge. Signs that prove to be more indicative to the status of a child's level of hydration include cool and clammy extremities, eagerness to drink, dry mouth and tongue, and a weak radial pulse.

Rehydration

Severely undernourished children should be hospitalized. ORS should be started as soon as possible. A standard ORS treatment with additional potassium should be given orally (preferred method) or using a nasogastric tube. An intravenous solution should be avoided since fluid overload may potentially cause heart failure and increase the risk of septicemia. By dissolving 7.5 g of potassium chloride in 100 ml of water, it is possible to prepare 1 mmol of potassium per milliliter of solution. Every 24 h, 4 ml/kg body weight should be given, mixed with food, for 14 days.

Feeding

Children with marasmus must limit their food intake to approximately 110 kcal/kg/day for the first week. On the other hand, children with kwashiorkor must begin a slow feeding treatment starting as low as 50 kcal/kg/day and work their way up to approximately 110 kcal/kg/day after approximately 1 week. This can be a difficult task since these children are often apathetic and have severe anorexia. The initial diets of all severely undernourished children must be given in small, frequent (every 2 h day and night), semiliquid doses. An example of an initial diet packet is 8 g skim milk powder, 6 g vegetable oil, 5 g sugar, and 100 ml water to make a high-energy (100 kcal/100 ml) meal with additional minerals, including 60 mg iron, 100 mg folic acid, and 200 000 units of vitamin A and vitamins B (complex), C, and D.

Conclusion

Diarrhea, a disease of fluid and electrolyte imbalance, is an important worldwide cause of morbidity and mortality among infants and children, especially in developing countries. However, it is also very much a nutritional disease. This is primarily because during periods of diarrhea, nutrient intake and absorption are dramatically decreased, which results in undernutrition even when sufficient food is available. The losses of nutrients affect growth rates, and where diarrhea occurs frequently the child may not grow properly. This is a cyclical pattern in that undernourishment in children makes them more prone to diarrhea. Their immune systems are less robust and the episodes affect them more than well-nourished children. Undernourishment and diarrhea can be a fatal combination that can result in a vicious cycle. This cycle requires intervention, sometimes at a treatment center if the case is severe enough. Therefore, is a matter of not only replacing the fluids and electrolytes but also of managing good feeding practices at all times before, during, and after the illness.

Sixty percent of the 10 million deaths among children younger than 5 years old are associated with malnutrition. Approximately 2 million of the deaths are due to diarrhea. Repeated episodes of diarrhea result in malnutrition, which in turn puts the child at an increased risk of recurrent infections, including diarrhea. To break this cycle, diarrheal episodes should be managed with appropriate fluid and nutritional therapy.

See also

COLON | Disorders; COLON | Nutritional Management of Disorders; LACTOSE INTOLERANCE; MALNUTRITION | Primary, Causes Epidemiology and Prevention; MALNUTRITION | Secondary, Diagnosis and Management; UNITED NATIONS CHILDREN'S FUND; VITAMIN A | Biochemistry and Physiological Role; WORLD HEALTH ORGANIZATION; ZINC | Deficiency in Developing Countries, Intervention Studies

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The previous version of this article (DIARRHOEAL (DIARRHEAL) DISEASES | Nutritional Factors) can be found online at doi:10.1016/B0-12-226694-3/00084-3.

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DIARRHOEAL (DIARRHEAL) DISEASES | Nutritional Factors

© 2005 Academic Press

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Updated October 2005.