The Role of Diet and Drugsã The Trustee of the Wellcome Trust 1998Reviewed by: Dr A Ashworth, Public Health Nutrition Unit, London School of Hygiene and Tropical Medicine, Dr R H Behrens, Hospital for Tropical Diseases, London and Dr W A M Cutting, Department of Child Life and Health, The University of Edinburgh, UKPicture: Correct nutrition is central to the management of malnutrition and diarrhoea.Copyright Image from Medicins Sans Frontieres.Image references ################ .\IMAGES\T45866.jpg Contents Click on the underlined text to jump tothat screen. Screen3Objectives 4Introduction 5Diarrhoea and Malnutrition 12Assessment 13Nutrition in the Treatment of AcuteDiarrhoea 20 Assessment 21Treatment of Diarrhoea with SevereMalnutrition 28Assessments 30Drugs in the Treatment of Diarrhoea 32Antimicrobials in the Treatment ofDiarrhoea 37 Antidiarrhoeal Drugs in theTreatment of Diarrhoea 42Assessment 43 Tutorial Assessment44 Summary Underlined text is interactive. Click on underlined text to view extra information or to jump to another screen. Picture: Breast feeding in an oral rehydration clinic. Breast feeding reduces the severity and duration of diarrhoea. Copyright Copyright Image from Guidelines for Conducting Clinical Training Courses at Health Centres and Small Hospitals (Transparency Set). Programme for Control of Diarrhoeal Diseases, World Health Organization 1992.Image references ################ .\IMAGES\T45262c.jpg Objectives At the end of this tutorial you should be able to: 1. show how diarrhoea and malnutrition interact 2. describe the role of nutrition in the treatment of a child with acute diarrhoea 3. summarize the management of a child with diarrhoea and severe malnutrition 4. give the indications for the antimicrobial treatment of diarrhoea 5. discuss the role of antidiarrhoeal drugs in adults and children Image references ################ Introduction Diarrhoea Diarrhoea is: · an increase in the number, volume and water content of stools · a global cause of much illness and death· a major factor in childhood malnutrition This tutorial is about the role of nutrition in diarrhoea, and the role of drugs in the treatment of diarrhoea. Picture: A young Bangladeshi woman being treated for suspected cholera. She should receive rehydration with early feeding and an appropriate antibiotic.Copyright Image from Cutting WAM. Diarrhoea morbidity and mortality Each year there are: · approximately 3.3 million deaths due to diarrhoea, 80% in children under 2 years of age · over 1 billion episodes of diarrhoea, most in the developing world · 5 - 10 million travellers affected by diarrhoea Image references ################ .\IMAGES\T44898.jpg Diarrhoea and Malnutrition Diarrhoea and MalnutritionImage references ################ Diarrhoea and Malnutrition - 1Diarrhoea reduces nutritionalstatus Diarrhoea in children in developing countries causes nutritional decline through: · reduced dietary intake · increased metabolism · direct losses from the bowel · reduced digestion and absorption of nutrients The impact of diarrhoea on nutritional status is greatest for: · persistent diarrhoea· recurrent episodes of acute diarrhoea Picture: The nutritional impact of persistent diarrhoea. This is a Bangladeshi child before (left) and after (right) persistent diarrhoea. Note the severe malnutrition.Copyright Images from Behrens RH. Persistent diarrhoea Persistent diarrhoea is: · watery or bloody diarrhoea that lasts at least 14 days · so closely linked to malnutrition that the two are often considered as a persistent diarrhoea- malnutrition syndromeImage references ################ .\IMAGES\T45345b.jpg Diarrhoea and Malnutrition - 2Reduced dietary intake due to diarrhoea Diarrhoea causes reduced intake of food through: · anorexia (see picture) · dilution of the child’s usual food by the carer· withholding of food completely by the carer What is the impact of these onfood intake?Picture: The multifactorial origins of anorexia due to diarrhoea.Enteric infection Nausea and Dehydration vomiting Abdominal distension Acute Acidosisphase response Hypo- kalaemia Anorexia Copyright Image from The Wellcome Trust. Anorexia Anorexia (lack of appetite): · is particularly associated with shigellosis and persistent diarrhoea · improves within 1 - 2 days of treatment of the underlying infection in most children · lasts for weeks or longer in a few children, with severe effects on their nutritional statusDilution of usual food Food given to a child with diarrhoea is often diluted with water in the belief that a more liquid diet will be easier to eat and digest. This practice: · is widespread in many cultures · reduces the nutritional concentration of the food · has no benefits· is not recommended (see screens 17 - 18) Withholding of food It is common to withhold solid food completely during diarrhoea to ‘rest the bowel’. This practice: · is widespread in many cultures · has no benefits· is not recommended Food should be withheld only for the first 4 - 6 hours of oral rehydration, after which it should be restarted (‘early refeeding’ - see screens 17 - 18).Impact on food intake The nutritional (energy) intake of children in developing countries is often reduced by 20 - 40% during an episode of diarrhoea compared with healthy children in the same setting. In many cases this reduction is restricted to solid foods and the intake of breast milk is not affected. Image references ################ .\IMAGES\Anorexia.gif Diarrhoea and Malnutrition - 3 The acute phase response. Increased metabolism due to diarrhoea Diarrhoea causes an increase in metabolism through: · the acute phase response (see picture) · repair of damaged bowel mucosa What is the impact of these on the metabolic rate? Direct losses from the bowel The exudate of inflammatory diarrhoea causes direct loss of nutrients from the bowel. Acute infection Release of cytokines Brain: Liver: Skeletal· fever · uptake ofmuscle: · anorexia amino acids · breakdown · acute phase · release of proteins amino acids Copyright Image from The Wellcome Trust. Acute phase response The acute phase response: · is a metabolic reaction to acute infection (eg. diarrhoea, measles, malaria, otitis media), trauma or surgery · has evolved to defend the body, eg. against microbial proliferation Repair of damaged mucosa Protein synthesis must be increased to repair any damage to the mucosa. Damage to the bowel mucosa by enteric pathogens varies. For example: · V. cholerae O1 causes no histologically visible damage · rotavirus kills enterocytes and causes subtotal villous atrophy · Shigella kills colonocytes and causes gross inflammation of the mucosa, villous atrophy and a mucopurulent exudateDirect losses A protein-losing enteropathy is characteristic of shigellosis. If dysentery is recurrent or persistent, significant amounts of protein can be lost.Acute phase proteinsThese proteins: · increase host resistance to infection · minimize tissue injury · promote tissue repair They include: · C-reactive protein · protease inhibitors, eg. a1-antitrypsin · coagulation proteins, eg. fibrinogen · complement proteins · transport proteins, eg. haptoglobinRelease of cytokines The cytokines of the acute phase response: · are released by macrophages and monocytes in response to infection · include interleukin 1 (IL-1), IL-6 and tumour necrosis factor a · regulate the inflammatory reaction Refer to the tutorial Diarrhoeal Diseases: Defence Mechanisms.Impact on metabolic rateThe impact of fever alone on metabolic rate is significant. Every 1 oC rise in body temperature above normal increases the metabolic rate, and therefore the energy requirements, by 4%. Image references ################ .\IMAGES\Acuteph.gif Diarrhoea and Malnutrition - 4Reduced digestion and absorption due to diarrhoea Diarrhoea causes reduced digestion and absorption of nutrients through: · damage to the bowel mucosa by enteric pathogens · reduced activity of disaccharidases, eg. lactase · reduced intestinal levels of conjugatedbile salts · more rapid transit of bowel contents What is the impact of these on absorption of nutrients? Picture: A typical stool from a patient with giardiasis. Giardia causes reduced absorption of nutrients, especially fats. This gives the stool a high fat content (steatorrhoea) and an oily appearance.Copyright Image from Tubbs HR. Lactase Lactase: · is a brush border enzyme in the microvilli of enterocytes · breaks down lactose into glucose and galactose Lactase deficiency: · is often due to an enteric pathogen damaging the microvilli · causes undigested lactose and fermented short chain fatty acids to build up in the lumen · results in clinically significant lactose intolerance in some children (see screen 16)Conjugated bile salts Enteric bacteria and some parasites (eg. Giardia) break down conjugated bile salts into free bile salts and acids. This deconjugation causes: · malabsorption of fats · inhibited active transport of sugars Bowel transit time More rapid transit of material through the gastrointestinal tract reduces the time for digestion and absorption of nutrients.Impact on nutrient absorptionDuring an episode of acute diarrhoea: · absorption of nutrients is reduced by about 30% · carbohydrate is absorbed better than fat or protein A reduction in nutrient absorption of 30% means that 70% of nutrients are still absorbed. This is why early feeding after initial rehydration is important. Image references ################ .\IMAGES\T22831.jpg Diarrhoea and Malnutrition - 5For picture legend. Malnutrition makes diarrhoea worse Malnutrition, especially severe malnutrition, predisposes to diarrhoea of increased: · duration · clinical severity· case fatality rate Does malnutrition increase the incidence of diarrhoea? Malnutrition predisposes to diarrhoea because it impairs defence mechanisms such as: · cell-mediated immunity · production of IgA · intestinal secretions · integrity of the bowel mucosa (see picture)Picture legend Pictures: Small bowel histology in the normal intestine (top) and persistent diarrhoea-malnutrition syndrome (bottom) in Gambian children. Severe malnutrition is associated with gross histological changes to the small bowel, including subtotal villous atrophy. Copyright Images from Behrens RH. Severity Severe diarrhoea is characterized by a high: · stool frequency, eg. 6 or more stools per 24 hours · stool volume · risk of rapid or severe dehydrationCase fatality rate Compared with well nourished children, those with pre-existing severe malnutrition are: · 20 - 60 times more likely to die during an episode of persistent diarrhoea · 4 - 10 times more likely to die during an episode of acute diarrhoea Intestinal secretions Severe malnutrition causes reduced secretion of: · gastric acid (hypochlorhydria) · mucus · bile · pancreatic juice For details refer to the tutorial Diarrhoeal Diseases: Defence Mechanisms. Small bowel mucosaSevere malnutrition is associated with characteristic histological changes to the small bowel mucosa. These include: · a thin mucosa, which favours enteric infection· subtotal villous atrophy · crypt hyperplasiaIncidence of diarrhoeaEpidemiological studies of the effect of pre-existing malnutrition on the incidence of diarrhoea: · are methodologically complex to perform and interpret · have not always given consistent results The current consensus is that pre-existing malnutrition: · may predispose to acute diarrhoea, although this is controversial · does predispose to persistent diarrhoea, because malnutrition is associated with increased duration of each diarrhoea episode Image references ################ .\IMAGES\T45340b.jpg Diarrhoea and Malnutrition - 6The vicious circle of diarrhoea and malnutrition The picture summarizes how diarrhoea and malnutrition interact to reinforce each other in a vicious circle. If this circle is not broken the child is likely to suffer:· recurrent episodes of acute diarrhoea · persistent diarrhoea · severe malnutrition · non-intestinal infections · death When is the risk of growth falteringgreatest? The route to diarrhoea, infection, severe malnutrition and death.DIARRHOEA Impaired defence mechanisms Malnutrition Measles Persistent diarrhoea- malnutrition Pneumonia DEATH Copyright Image from The Wellcome Trust. Diarrhoea and malnutritionThe link between diarrhoea and malnutrition is so close that diarrhoea can be considered as a ‘nutritional’ disease nearly as much as one of fluid and electrolyte loss.Death The immediate cause of death in a child weakened by diarrhoea and severe malnutrition is often a non-intestinal infection such as: · pneumonia · septicaemia · measles · malaria · tuberculosisGrowth falteringFaltering of growth due to the diarrhoea-malnutrition cycle is especially likely to begin at weaning. At this critical time, introducing complementary foods too: · early (before 4 months of age) increases the risk of diarrhoea · late (after 6 months of age) increases the risk of malnutrition The nutritional effects of poor weaning practice can extend for several years, well after the child is completely weaned. Image references ################ .\IMAGES\Diadeath.gif To return to the start of the section. How does diarrhoea cause malnutrition? Click your mouse on a box below. Hold the mouse down and drag the box to the correct column. Cause of malnutrition Reduced intakeIncreased Reduced absorption of food metabolism Direct lossesof nutrients Diarrhoea and Malnutrition: AssessmentWithholding of food Low levels ofconjugated bile salts Anorexia Inflammatory exudate Acute phase response Repair of damaged bowel Yes. That's right. Yes. That's right. Yes. That's right. Yes. That's right. Yes. That's right. Yes. That's right. No. That's wrong. Try again. Well done. You have nowfinished this assessment.Image references ################ Nutrition in the Treatment of Acute Diarrhoea Nutrition in the Treatment of Acute DiarrhoeaImage references ################ Nutrition in the Treatment of Acute Diarrhoea - 1Nutrition and diarrhoea Nutritional treatment is a central part of the management of diarrhoea. Diet is important: · during the diarrhoea episode · after the diarrhoea has ended During an episode of diarrhoea: · breast feeding should be continued · complementary foods should be restarted after initial oral rehydration therapy (ORT) Important notes. Summary of the treatment ofacute diarrhoea 1. Prevention or treatment of dehydration. 2. Appropriate nutritional management. 3. Antimicrobial treatment of specific enteric infections. 4. Treatment of associated infections or complications.Restarting food Children given ORT (WHO diarrhoea ‘treatment plan B’) should restart complementary feeding after 4 - 6 hours of oral rehydration. After this period of ORT many children will be fully rehydrated. Note that children with no signs of dehydration (‘treatment plan A’) should: · receive home available fluids to prevent dehydration · continue feeding throughout the diarrhoeaImportant notesThis section describes diets appropriate for during and after acute diarrhoea. It does not generally cover nutritional management of a child with: · persistent diarrhoea - defined diets are needed (refer to the tutorial Diarrhoeal Diseases: Persistent Diarrhoea) · diarrhoea and severe malnutrition - specialist inpatient management is essential (see screens 21 - 27) Image references ################ Nutrition in the Treatment of Acute Diarrhoea - 2Breast feeding during diarrhoea Breast feeding throughout an episode of acute diarrhoea reduces the: · stool volume (see graph) · stool frequency · volume of ORS solution needed for rehydration · duration of diarrhoea · risk of diarrhoea worsening the child’s nutritional status How does breast milk have these effects? Breast feeding should be continued throughout acute and persistent diarrhoea. Graph: Stool volumes in Burmese children aged6 - 24 months with acute diarrhoea given ORT alone or ORT with breast feeding. Volume (ml/kg/6 hours)24201612840 ORT alone ORT and breast 06121824303642Hours Continued breast feeding A child with diarrhoea should be: · allowed to breast feed as much as he or she wants · encouraged to breast feed more than usualCopyright Image from The Wellcome Trust modified from Khin-Maung-U, Nyunt-Nyunt-Wai, Myo-Khin, Mu-Mu-Khin, Tin-U, Thane-Toe. BMJ 1985;290:587-9.Stool volume The reduction in stool output means that the risk of dehydration is reduced.How does breast milk have these effects?The beneficial effects of breast milk on the severity and duration of diarrhoea may reflect: · increased clearance of the enteric infection· more rapid repair of the damaged bowel These could be due to the following factors in breast milk: · antibodies - secretory IgA and IgM · immune cells - macrophages, neutrophils and lymphocytes · growth factors and hormones · non-specific factors - lysozyme, lactoferrin and peroxidase Image references ################ .\IMAGES\Burmabf.gif Nutrition in the Treatment of Acute Diarrhoea - 3Non-breast milk during diarrhoea Feeding with animal milk or formula milk has been the subject of over 20 clinical trials.These show that in acute diarrhoea: · non-breast milk is rarely associated with lactose intolerance· lactose free formula milk is rarely necessary What are the recommendations for persistent diarrhoea? The vast majority of children with acute diarrhoea can be given undiluted non-breast milk after 4 - 6 hours of ORT.Picture: Non-breast milk should be given by cup and not from a bottle. Copyright Image from The Wellcome Trust. Lactose intoleranceMilk given to a child with clinically significant lactose intolerance causes: · an increase in stool frequency · recurrence or worsening of dehydration · weight loss Clinically significant lactose intolerance is unusual in children with acute diarrhoea.Non-breast milk in persistent diarrhoeaLactose intolerance is more common in persistent than in acute diarrhoea. Lactose intake in non-breast fed children with persistent diarrhoea may need to be reduced by giving: 1. yogurt, which contains less lactose than animal or formula milk 2. lactose free formula milk For details refer to the tutorial Diarrhoeal Diseases: Persistent Diarrhoea.Lactose free formula milk Lactose free formula milk: · has no benefits over animal milk or standard formula milk in most children with acute diarrhoea · is expensive and not widely available Image references ################ .\IMAGES\Kidsage2.jpg Nutrition in the Treatment of Acute Diarrhoea - 4Feeding solid food during acute diarrhoea Numerous clinical trials show that restarting complementary feeding after initial rehydration causes: · absorption of significant amounts of nutrients · a reduction in nutritional decline* · more rapid recovery of intestinal function* *Compared with diluting or withholding food. Does early feeding have an impact on diarrhoea? Early feeding with complementary foods should be restarted after 4 - 6 hours of ORT.Picture: Feeding is important in the management of diarrhoea. This is a child taking solid foods after initial rehydration for acute diarrhoea.Copyright Image from United Nations Children's Fund, India. Intestinal functionWithholding of food for more than 4 - 6 hours of initial rehydration can cause: · reduced secretion of digestive enzymes · slow enterocyte multiplication and differentiation, causing structural changes to the small bowel These can mark the start of nutritional decline due to diarrhoea.Early feeding after 4 - 6 hours of ORTDelaying the reintroduction of solid food for a few hours helps to avoid possible consequences of malabsorption of the food. These consequences include: · acidosis · increased fluid loss, worsening the diarrhoea · electrolyte imbalance · possible uptake of intact proteins by damaged bowel, leading to protein sensitivity Impact on diarrhoea Early reintroduction of complementary foods: · has no significant impact on the severity of diarrhoea; stool volume may even be increased · reduced the duration of diarrhoea in some studies The main justification for early feeding is to prevent nutritional decline. Image references ################ .\IMAGES\T45967.jpg Nutrition in the Treatment of Acute Diarrhoea - 5Complementary foods during acute diarrhoea A child with acute diarrhoea should be given food that: · is culturally acceptable · is readily available · is high in energy content · provides adequate essential micronutrients · is well cooked · is mashed or ground· contains added vegetable oil Non-breast milk should be given undiluted and mixed with cereal. How often should food be given? Picture: Foods suitable for giving to a child with acute diarrhoea include cereals and vegetables. These must be prepared properly for feeding to small children. Which other foods can be given? Copyright Image from Chitrabani Society. Other foodsDepending on availability, the following foods should also be given: · meat· fish Sources of animal protein. · egg · bananas · green coconutwater · fresh fruit juice Good sources of potassium. Frequency of feedingThe aim is to encourage the child to take as much nutritious food as possible. A child is more likely to take meals given little and often: · in small amounts · every 3 or 4 hours (at least 6 times a day)Acute diarrhoeaThe foods described and pictured are suitable for a child with acute diarrhoea but not for children with: · persistent diarrhoea and moderate or severe malnutrition · acute diarrhoea with severe malnutrition These children should be treated in hospital.Mashed or ground This makes the food easier for young children to swallow.Added vegetable oil Picture: Adding vegetable oil to food for a child with diarrhoea. Image from United Nations Children's Fund, India. A small amount of vegetable oil (5 - 10 ml): · should be added to each serving of cereal · increases the energy content of the food because oil (fat) contains a lot of energy (Alternatives to vegetable oil are margarine, butter and ghee.)Mixing milk with cerealMixing non-breast milk with cereal: · improves absorption of lactose by the intestine · reduces the risk of lactose intolerance Image references ################ .\IMAGES\T25662.jpg .\IMAGES\T45966p.jpg Nutrition in the Treatment of Acute Diarrhoea - 6Feeding after diarrhoea Infections such as diarrhoea cause an acute fall in nutritional status, after which catch-up growth (see graph) is needed to return the child’s growth curve to a healthy level. Catch-up growth: · can be very rapid· requires a diet (as described on screen 18) that contains: - a high energy content - an appropriate amount of protein- a range of micronutrients Remember.An extra meal a day should be given for at least 2 weeks after an episode of acute or persistent diarrhoea.Weight (kg) Catch-up growth Diarrhoea Time (months) Picture:A growth chart showing a fall in nutritional status due to repeated episodes of acute diarrhoea, followed by a period of catch-up growth.Copyright Image from The Wellcome Trust. Rapid growth During catch-up growth, weight gain can be up to 20 times faster than in a healthy child of the same age. Remember Children recovering from diarrhoea with severe malnutrition need a special diet during their catch-up growth (see screen 27).Image references ################ .\IMAGES\Growth1.gif Nutrition in the Treatment of Acute Diarrhoea: AssessmentAre the following statements about nutrition during diarrhoea true or false? Click on the True or False button for each statement. To return to the start of the section. During an episode of acute diarrhoea: 1. breast feeding reduces the severity and duration of diarrhoea2. lactose free formula milk must be given to non-breast fed infants3. complementary foods should be withheld for 24 hours4. specialist diets are needed for most childrenCorrect Breast feeding during an episode of diarrhoea reduces the: · severity of diarrhoea · duration of diarrhoea Breast feeding throughout the episode should be encouraged.Incorrect Text 11 pt Arial dark blue goes here Incorrect Breast feeding during an episode of diarrhoea reduces the: · severity of diarrhoea · duration of diarrhoea Breast feeding throughout the episode should be encouraged.Correct Text 11 pt Arial dark blue goes here Correct Text 11 pt Arial dark blue goes here Incorrect During an episode of acute diarrhoea, children who are not breast fed: · rarely need lactose free formula milk - clinically significant lactose intolerance is uncommon · should be fed their normal cow’s milk or formula milk undiluted, after initial rehydrationIncorrect Text 11 pt Arial dark blue goes here Correct During an episode of acute diarrhoea, children who are not breast fed: · rarely need lactose free formula milk - clinically significant lactose intolerance is uncommon · should be fed their normal cow’s milk or formula milk undiluted, after initial rehydrationCorrect Text 11 pt Arial dark blue goes here Incorrect Complementary feeding should be restarted after initial rehydration because this causes: · a reduction in any nutritional decline due to diarrhoea · more rapid recovery of intestinal function ‘Resting the bowel’ for more than 4 - 6 hours of ORT is nutritionally harmful and not recommended.Incorrect Text 11 pt Arial dark blue goes here Correct Complementary feeding should be restarted after initial rehydration because this causes: · a reduction in any nutritional decline due to diarrhoea · more rapid recovery of intestinal function ‘Resting the bowel’ for more than 4 - 6 hours of ORT is nutritionally harmful and not recommended.Correct Incorrect Children with acute diarrhoea should be given food that is: · culturally acceptable · readily available · nutritious· appetizing More specialist diets are needed for children treated in hospital with: · persistent diarrhoea and moderate or severe malnutrition · acute diarrhoea and severe malnutritionIncorrect Text explaining the answer (11-pt plain blue) Correct Children with acute diarrhoea should be given food that is: · culturally acceptable · readily available · nutritious· appetizing More specialist diets are needed for children treated in hospital with: · persistent diarrhoea and moderate or severe malnutrition · acute diarrhoea and severe malnutrition Image references ################ Treatment of Diarrhoea with Severe Malnutrition Treatment of Diarrhoea with Severe MalnutritionImage references ################ Treatment of Diarrhoea with Severe Malnutrition - 1Clinical effects of severe malnutrition Severe malnutrition affects every organ in the body. Complications include: · hypoglycaemia and hypothermia · dehydration due to diarrhoea (see picture) · loss of homeostasis· electrolyte imbalance· infections, eg. pneumonia These complications need management in hospital in addition to treating the underlying deficits of energy, protein and micronutrients. How serious is severe malnutrition? Picture: A Jamaican child with diarrhoea and severe malnutrition being rehydrated by nasogastric tube. Intravenous rehydration of a child with severe malnutrition can precipitate congestive heart failure. How is severe malnutrition defined? Copyright Image from Golden M. Hypoglycaemia and hypothermiaIn a child with severe malnutrition: · hypoglycaemia is defined as a blood glucose level of less than 3 mmol/l · hypothermia is defined as an axillary temperature of less than 35OC or a rectal temperature of less than 35.5OC Hypoglycaemia and hypothermia in severe malnutrition usually: · occur together · are associated with infection · are prevented by frequent feedingDiarrhoea in severe malnutrition Many children with severe malnutrition pass frequent, small, loose or poorly formed stools. These are not considered to be diarrhoea. Diarrhoea is diagnosed only if the stools are: · profuse or watery, carrying a risk of dehydration · bloody, requiring antibiotic treatment for dysenteryLoss of homeostasisChildren with severe malnutrition lose homeostatic control over their metabolism. Initial treatment must therefore be cautious, such as: · limiting nutritional intake during the early phase of treatment · avoiding intravenous rehydration except for hypovolaemic shockElectrolyte imbalanceChildren with severe malnutrition generally have: · high body levels of sodium (Na+) · low body levels of potassium (K+) These electrolyte imbalances: · put the child at high risk of death from heart failure - this is important for rehydration and feeding · require specific treatment· can take 2 weeks or longer to correctHow serious is severe malnutrition?Case fatality rates for treatment in hospital or nutrition rehabilitation units vary widely, ranging from: · over 20% - unacceptably high · 11 - 20% - poor · 5 - 10% - moderate · under 5% - good The case fatality rate is often slightly higher for kwashiorkor than for marasmus.Definition of severe malnutrition Severe malnutrition is defined for the purposes of treatment as severe wasting (less than 70% weight for height) and/or oedema. Severe malnutrition, also called ‘protein-energy malnutrition’, classically presents as two extreme syndromes: · marasmus - characterized by severe wasting · kwashiorkor - characterized by oedema Children with marasmus, kwashiorkor and the intermediate marasmic kwashiorkor are not differentiated for purposes of management. All have ‘severe malnutrition’ and are treated in a similar way. Image references ################ .\IMAGES\T27811b.jpg Treatment of Diarrhoea with Severe Malnutrition - 2 Phase Stabilization Rehabilitation DayDays Weeks1 - 22- 7+ 2 - 6 1. Management ofhypoglycaemia 2. Management ofhypothermia 3. Management of dehydration 4. Correction of electrolyte imbalance 5. Prevention or treatmentof infection 6. Correction of micronutrientdeficiency7. Cautious feeding 8. Facilitation of catch-up growth 9. Sensory stimulation 10. Preparation for follow-up Steps in the treatment of severe malnutrition Inpatient management of a child with severe malnutrition follows ten steps (see picture). These steps cover two phases: 1. stabilization2. rehabilitation When is the change to rehabilitation made?Picture: Steps in the management of a child with severe malnutrition. This tutorial gives a summary of steps 3 - 8. With iron No iron Stabilization phaseDuring the stabilization phase, the acute medical conditions are managed. For example: · dehydration · infection Feeding during this period is cautious, because too much fluid and food can cause death from: · metabolic stress · heart failureRehabilitation phasePicture: Encouraging a child with severe malnutrition to eat. Image from MERLIN courtesy of Lorie J. During the rehabilitation phase, catch-up growth is promoted with a diet high in: · energy· protein · micronutrientsChange to rehabilitationThe best indicator for starting the catch-up diet is return of the child’s appetite. This usually occurs about 1 week after the start of treatment. Image references ################ .\IMAGES\Tenstep2.gif .\IMAGES\T45818p.jpg Treatment of Diarrhoea with Severe Malnutrition - 3 Oral Rehydration Solution for Children with Severe Malnutrition1 Rehydration Incorrect rehydration of a severely malnourished child can cause heart failure due to: · sodium overload or potassium deficiency · overhydration These children should be given: · modified ORS solution (see table) if they have watery diarrhoea· intravenous rehydration only for hypovolaemic shockRemember. Correction of electrolyte imbalance A combined electrolyte and mineral solution should be added to: · modified ORS solution (see table) · starter and catch-up feeds Ingredient Amount for 2 litresStandard ORS solution A 1 litre sachet Sucrose 50 g Electrolyte and mineral 40 ml of stock solution solution (see below) 1. This rehydration solution (‘ReSoMal’) is prepared by making half strength standard ORS solution, then adding sucrose and electrolyte-mineral solution as shown. How does this solution differ from standard ORS solution? Modified ORS solution versus standard ORSCompared with standard ORS solution, this modified ORS solution contains: · less Na+ (45 versus 90 mmol/l) · more K+ (40 versus 20 mmol/l) · added sucrose (25 g/l) - in addition to the glucose in standard ORS solution · added minerals: - magnesium (Mg2+ at 3 mmol/l) - zinc (Zn2+ at 300 mmol/l) - copper (Cu2+at 45 mmol/l)Rehydration treatment Severe malnutrition makes assessment of dehydration difficult. For details refer to the tutorial Diarrhoeal Diseases: Clinical Assessment. Oral rehydration with modified ORS solution should therefore be given to a severely malnourished child with: · any signs of dehydration · watery diarrhoea, because of the risk of dehydration developingOverhydrationIt is important to be aware of the signs of overhydration, such as: · increased respiration rate · increased pulse rate · puffy eyelids · increased oedema If a child develops signs of overhydration: 1. rehydration should be stopped 2. the patient should be reassessed after 1 hourOral rehydration in severe malnutritionModified ORS solution should be given by mouth or nasogastric tube at the rate of: 1. 5 ml/kg every 30 minutes for the first 2 hours 2. 5 - 10 ml/kg every 60 minutes for the next 4 - 10 hours These rates are slower than ORT in children without severe malnutrition. Breast feeding should be continued. Intravenous rehydration in severe malnutritionA child with signs of hypovolaemic shock (eg. cool extremities, rapid weak pulse, reduced consciousness or lethargy) and a history of watery diarrhoea should be given intravenous rehydration: · at 15 ml/kg over the first hour, with frequent monitoring of the response · with one of these solutions, in order or preference: 1. Ringer’s lactate with 5% dextrose 2. half-normal saline with 5% dextrose3. Ringer’s lactate Severely malnourished children with severe dehydration should: · respond to initial intravenous rehydration, eg. by a fall in respiration and pulse rates · be given a further 15 ml/kg intravenously over the next hour before switching to oral rehydrationElectrolyte and Mineral SolutionIngredient Amount (g/2.5 litres) Final concentration (mmol/l)1 Potassium chloride224 24 Tripotassium citrate81 2 Magnesium chloride 76 3 Zinc acetate 8.2 0.3 Copper sulphate 1.4 0.0451. The final concentration after dilution of the stock 50-fold in modified ORS solution, or in starter or catch-up feed. Image references ################ Treatment of Diarrhoea with Severe Malnutrition - 4An egg of Ascaris lumbricoides in a faecal specimen. This finding is an indication for treatment with mebendazole.Prevention or treatment of infection Severely malnourished children usually have one or more infections but fail to show signs, eg. fever. All should be given: · broad spectrum antibiotics· measles vaccination Appropriate treatment for specific diagnosed infections should also be given, such as: · shigellosis· cholera· giardiasis· parasitic worms· tuberculosis Note. Copyright Image from Liverpool School of Tropical Medicine photo by Stich A. Broad Spectrum Antibiotics in Severe Malnutrition (WHO 1998)Clinical conditionAntibiotics Regimen No complicationsTrimethoprim1 40 mg twice daily for 5 days plus Sulphamethoxazole1 200 mg twice daily for 5 days Severely ill orAmpicillin2 50 mg/kg every 6 hours for 2 days complications3 then Amoxycillin1 15 mg/kg every 8 hours for 5 days plus Gentamicin2 7.5 mg/kg once daily for 7 days 1. Oral. 2. Intramuscular or intravenous. 3. A severely ill child will be apathetic or lethargic. If the child fails to improve within 48 hours, intramuscular or intravenous chloramphenicol (25 mg/kg every 6 hours for 5 days) should be added.Measles vaccinationMeasles vaccine should be given to a child who: · is aged above 6 months · has not already been immunized against measlesTreatment for giardiasisMetronidazole should be given to a child with both: 1. diarrhoea persisting beyond the first week of hospital treatment 2. microscopic diagnosis of Giardia lamblia cysts or trophozoites in the stool For doses see screen 33.Treatment for parasitic worms Infection with parasitic worms (eg. Trichuris, Ascaris - see picture) is diagnosed by finding eggs on stool microscopy. Treatment is with mebendazole given: · orally· at a dose of 100 mg twice daily · for 3 days NoteMany children with severe malnutrition have bacterial overgrowth of the intestinal tract. For this reason many doctors routinely give metronidazole at 7.5 mg/kg three times a day for7 days. Image references ################ .\IMAGES\T42366.jpg Treatment of Diarrhoea with Severe Malnutrition - 5Hours (day and night) 121086420 Micronutrients and cautious feeding For details of micronutrient feeding. During stabilization the child should be fed cautiously with: · small frequent feeds of a milk based starter formula (F-75) · oral or nasogastric feeding· 130 ml/kg/day (see picture) of F-75, providing: - 100 kcal/kg/day - 1 - 1.5 g protein/kg/day · continued breast feeding How is the child’s progress monitored? Picture: A typical feeding schedule during the stabilization phase. This schedule is repeated day and night, starting with 12 feeds in 24 hours. 22 ml/kg 16 ml/kg 11 ml/kg Day 1 -2Days 3 - 5Days 6 - 7+ Copyright Image from The Wellcome Trust. Cautious feedingThe aim in the stabilization phase is to: · start feeding as soon as possible, eg. after 6 hours of oral rehydration (ORT may continue for longer) · provide just enough protein and energy to maintain basic physiological processes During this phase: · the child’s physiology is fragile and has poor homeostasis · too rapid feeding can cause metabolic stress, heart failure and death Recipe for Starter Formula (F-75)1Ingredient Amount per litre Dried skimmed milk2 25 g Sucrose3 100 g Vegetable oil 30 g Electrolyte and mineral 20 ml stock solution 1. This formula has a low osmolarity and a low lactose concentration. Each 100 ml provides 75 kcal (hence ‘F-75’) and 0.9 g protein.2. Other types of milk, eg. fresh cow’s milk, can be used instead. 3. Cereal flour can be used to replace some of the sucrose.Oral or nasogastric feedingChildren should be encouraged to feed from a cup if possible. Those who are very weak can be fed using a: · spoon · dropper · syringe - with the needle removed · nasogastric tube - to ‘top up’ if intake by the above routes is less than 80 kcal/kg/day 130 ml/kg/dayIn children with severe oedema: · ‘true’ body weight is lower than the measured body weight ·the volume of F-75 is reduced from 130 to 100 ml/kg/dayBreast feeding If the child is breast feeding, this should: · continue during treatment · be done after the child has been given the starter formulaCorrection of micronutrient deficienciesMicronutrient deficiencies are corrected by giving: · multivitamin supplements - at least twice the recommended daily allowance · folic acid - 5 mg on day 1, then 1 mg on each following day · zinc - 2 mg/kg/day*· copper - 0.2 mg/kg/day* · vitamin A - a large single dose on day 1 (in addition to that in the multivitamin supplement) * From the electrolyte and mineral solution added to the starter feed. Even in a child with anaemia, iron should be given: 1. only when there is a return of appetite and gain in weight - iron can make infections worse and increase the risk of death 2. at a dose of 3 mg/kg/dayMonitoring progressThe following should be monitored during the stabilization phase: · amounts of food offered and left over · vomiting · stool frequency and consistency - diarrhoea should gradually diminish · daily body weight - children with oedema should lose weight as the oedema resolves Image references ################ .\IMAGES\Smfeed.gif Treatment of Diarrhoea with Severe Malnutrition - 6 Feeding during catch-upgrowth During catch-up growth the child should be fed: · frequent feeds (every 4 hours) of a milk based catch-up formula (F-100) · about 200 ml/kg/day of F-100, providing: - 150 - 220 kcal/kg/day - 4 - 6 g protein/kg/day · continued breast feeding How is the child’s progress monitored?Picture: Feeding during catch-up growth. How is the transition from starter to catch-up formula made?Copyright Image from MERLIN courtesy of Lorie J. Transition to catch-up diet A gradual transition from cautious feeding to catch-up diet is made by: 1. replacing starter formula (F-75) with an equal volume of catch-up formula (F-100) for 2 days 2. progressively increasing the amount of each feed by 10 ml until the child will eat no more, often at about 30 ml/kg/feedCatch-up growth The aim in this phase is to: · give a very high intake of energy and nutrients · promote rapid catch-up growth, up to 20 times faster than in a healthy child of the same age. Remember: Readiness to enter this phase is indicated by the return of the child’s appetite, usually after 1 week of treatment.Monitoring of progress Progress during the catch-up phase is assessed by the rate of weight gain. This is monitored by: 1. weighing the child each morning before a feed 2. plotting the weight on a chart 3. calculating and recording the weight gain each week - most children gain 10 - 15 g/kg/day Image references ################ .\IMAGES\T45819.jpg Treatment of Diarrhoea with Severe Malnutrition: Assessment - 1A 9-month-old boy presents with watery diarrhoea and severe malnutrition. You decide to give oral rehydration.What are the main problems with rehydration? For the answer. How are these problems solved? For the answer. When would intravenous rehydration be indicated? For the answer. To return to the start of the section. Answer: Problems with rehydrationProblems with rehydration in a severly malnourished child include: · difficulty in assessing the degree of dehydration · the risk of precipitating heart failure through: - sodium overload and potassium deficiency - overhydrationAnswer: Overcoming the problems of rehydrationProblem How problem is solved Assessing the degree Giving ORT to a child with any signs of dehydrationof dehydration or with watery diarrhoea Sodium overload and Modified ORS solution with less Na+ and more K+ potassium deficiency than standard ORS solution Overhydration Slower ORT than in a well nourished child Stricter indications for intravenous rehydration Clinical assessment for signs of overhydration Answer: Intravenous rehydrationIntravenous rehydration in a child with severe malnutrition is indicated only for hypovolaemic shock. The signs are: · cool and moist hands or feet · rapid weak pulse · reduced consciousness or lethargy · slow capillary refilling of nailbeds (longer than 2 seconds) Image references ################ Phase Stabilization Rehabilitation DayDays Weeks1 - 22- 7+ 2 - 6 1. Management ofhypoglycaemia 2. Management ofhypothermia 3.4. Correction of electrolyte imbalance 5. 6. 7. Cautious feeding 8.9. Sensory stimulation 10. Preparation for follow-up Complete the diagram, which summarizes the management of a child with diarrhoea and severe malnutrition. Click your mouse on a box below. Hold the mouse down and drag the box to the correct place within the diagram. To return to the start of the section.With iron No iron Treatment of Diarrhoea with Severe Malnutrition: Assessment - 2Facilitation of catch-up growth Correction of micronutrient deficiency Prevention or treatmentof infection Management of dehydration Yes. That's right. Yes. That's right. Yes. That's right. Yes. That's right. No. That's wrong. Try again. Well done. You have now finished this assessment.Image references ################ .\IMAGES\Tenstep2.gif Drugs in the Treatment of Diarrhoea Drugs in the Treatment of DiarrhoeaImage references ################ Drugs in the Treatment of Diarrhoea - 1Drugs and diarrhoea A wide range of drugs are used - and misused - in the management of diarrhoea. Antidiarrhoeal drugs Antidiarrhoeal drugs vary in efficacy (see screens 37 - 41) and are not generally recommended, especially not in children. They include: · antimotility drugs, eg. loperamide· adsorbents, eg. kaolin · antisecretory drugs· other agents, eg. bismuth subsalicylate Antimicrobials Antimicrobials are indicated for specific enteric infections (see screen 35). They are not an alternative to rehydration. They include:· antibiotics · antiparasitic agentsHow important are drugs in the treatment of diarrhoea?Antimicrobials An effective antimicrobial given promptly: · cures the enteric infection causing the diarrhoea · reduces the duration and severity of diarrhoea · is not an alternative to rehydration and early feeding Antidiarrhoeal drugsThese drugs aim to improve the symptoms of diarrhoea by: · reducing stool frequency · reducing stool volume · improving stool consistency Antidiarrhoeal drugs: · do not cure the underlying enteric infection · are not a replacement for rehydration and appropriate antibiotic therapyHow important are drugs?Antimicrobials are indicated for some patients with diarrhoea (eg. those with cholera and shigellosis) and not in others (eg. those with viral diarrhoea). However, all patients with diarrhoea should receive: · prevention or treatment of dehydration · appropriate nutritional management Image references ################ Antimicrobials in the Treatment of Diarrhoea Antimicrobials in the Treatment of DiarrhoeaImage references ################ Antimicrobials in the Treatment of Diarrhoea - 1The role of antimicrobials Antimicrobials should not be routinely given to patients with diarrhoea. The only enteric infections for which antimicrobial treatment is indicated (WHO 1995) are: · shigellosis · cholera (see picture) · amoebic dysentery · persistent diarrhoea due to Giardia What are the indications for treatment in each case?Picture: Rehydration of a 2-year-old Bangladeshi child with cholera. Antibiotics for cholera reduce the duration and severity of diarrhoea, but are not a substitute for rehydration and early feeding.Copyright Image from Cutting WAM. ShigellosisAntibiotics for the treatment of shigellosis include: · ampicillin · trimethoprim-sulphamethoxazole · nalidixic acid · pivmecillinam · fluoroquinolones (see screen 35) For details of doses refer to the tutorial Diarrhoeal Diseases: Acute Bloody Diarrhoea. The choice of antibiotic depends on the: · resistance of local strains (see screen 34) · availability · cost Cheapest Most expensive CholeraAntibiotics for the treatment of cholera include: · doxycycline - in patients over12 years of age · tetracycline· trimethoprim-sulphamethoxazole · erythromycin · furazolidone For details of doses refer to the tutorial Diarrhoeal Diseases: Acute Watery Diarrhoea.Preferred Alternatives Oral Treatments for Amoebic Dysentery (WHO 1994) DrugDose Regimen Children Metronidazole10 mg/kg 3 times a day for 5 days1 Adults Metronidazole750 mg 3 times a day for 5 days1 1. The duration of treatment is 10 days for severe disease.Oral Treatments for Giardiasis (WHO 1995)Drug Dose Regimen Children Metronidazole5 mg/kg 3 times a day for 5 days Adults Metronidazole250 mg 3 times a day for 5 days Children Tinidazole 50 mg/kg1 Single dose and adults 1. The maximum dose to be given is 2 g.Indications for Antimicrobials (WHO 1995)DiagnosisIndication Shigellosis Loose or watery stools that contain visible red blood1 Cholera Severe dehydration due to acute watery diarrhoea in apatient aged over 5 years1 or Acute watery diarrhoea in a patient aged over 2 yearsduring a cholera outbreak1 Amoebic dysentery Microscopic detection in the stool of Entamoeba histolyticatrophozoites containing red blood cells GiardiasisMicroscopic detection in the stool of Giardia lamblia cystsor trophozoites in a patient with persistent diarrhoea 1. These are the criteria for a presumptive clinical diagnosis where laboratory facilities are not available. Shigellosis can also be diagnosed from a history of bloody stools reported by the child’s mother. Ameobic dysentery can also be diagnosed if two different antibiotics normally effective against Shigella have failed. Image references ################ .\IMAGES\T44896a.jpg Antimicrobials in the Treatment of Diarrhoea - 2Antimicrobial resistance in Shigella Resistance of Shigella, especially S. dysenteriae, to antibiotics: · is a growing problem in many developing countries (see map) · can spread rapidly between strains via plasmids· is favoured by the indiscriminate use of antibiotics · now includes multiply resistant strains· drives the search for new antibiotics suchas fluoroquinolones What are the effects of worsening antibiotic resistance? Map: Resistance of S. dystenteriae to antibiotics in selected African countries.Ethiopia Burundi Zaire Zambia Resistance to: AmpicillinTMP-SMXNalidixic acid Copyright Image from The Wellcome Trust based on data from Shears P. Ann Trop Med Parasitol 1996;90:105-14. Rapid spread of resistance In Bangladesh, for example, nalidixic acid was: · introduced for the treatment of shigellosis in 1986 · ineffective against over half of all S. dysenteriae type 1 isolates at one centre by 199 Multiply resistant strains S. dysenteriae type 1 in some countries is resistant to all of: · ampicillin · trimethoprim-sulphamethoxazole · nalidixic acid The only options for treatment of such strains at present are the very expensive antibiotics: · pivmecillinam · fluoroquinolones - currently not licensed for use in children (see screen 35) Effects of resistance Worsening antibiotic resistance causes treatment failures. This increases the risk of: · complications and death (higher case fatality rate) for the individual · epidemic spread of shigellosis for the community Resistance also increases the cost of treatment as more expensive antibiotics (eg. pivmecillinam and fluoroquinolones) must be used. Image references ################ .\IMAGES\Sdafr.gif Antimicrobials in the Treatment of Diarrhoea - 3Fluoroquinolones for the treatment of shigellosis Use of the fluoroquinolone antibiotics:· reduces the severity and duration of shigellosis · has so far not selected for resistant strains More widespread use of these drugs is limited by the: · high cost· possible adverse effects in children· risk of selecting for resistance Fluoroquinolones are not currently licensed for use in children under 15 years of age.Picture: A bloody stool. This finding is an indication for giving antibiotics against shigellosis.Copyright Image from Bennish M. FluoroquinolonesThis group of antibiotics are closely related to the quinolone drug nalidixic acid. Fluoroquinolones include: · ciprofloxacin · norfloxacin · enoxacinResistance Resistance of Shigella to fluoroquinolones: · is so far very limited · is mediated by genes on the chromosome rather than on a plasmid · may spread less rapidly than resistance to other antibiotics High cost A course of treatment with a fluoroquinolone costs 4 - 8 times as much as a course of nalidixic acid.Adverse effects in childrenConcerns about safety in children are based on experiments in juvenile dogs and mice, in which high doses of fluoroquinolones caused cartilage damage. However, nalidixic acid (which is licensed for use in children): · causes similar effects to fluoroquinolones in experimental animals · has been widely used in children without reports of major adverse effects Failure to license fluoroquinolones for use in children, especially as resistance of Shigella to other antibiotics rises, may thus be over-cautious. Image references ################ .\IMAGES\T45899.jpg Antimicrobials in the Treatment of Diarrhoea - 4Antibiotics for Laboratory Diagnosed Diarrhoea Cultured bacterium Commonly used antibiotics Shigella1 Ampicillin Trimethoprim-sulphamethoxazole Nalidixic acid Ciprofloxacin2 Vibrio cholerae1Doxycycline2 Tetracycline Trimethoprim-sulphamethoxazole Erythromycin Furazolidone Salmonella Ciprofloxacin2(uncomplicated disease)Campylobacter Erythromycin Ciprofloxacin2 Clostridum difficile Vancomycin Metronidazole Other antibiotics Treatment with the antibiotics shown in the table can be given when: · facilities exist for laboratory diagnosis· the results of culture are available in time· the drugs shown are available and can be afforded In practice these conditions are least likely to be met in developing countries. For table footnotes.Results available in timePicture: A culture of V. cholerae O1. Image from Centers for Disease Control and Prevention. Culture of bacterial pathogens from a stool sample: · generally takes 2 - 3 days · may not provide results in time because: - treatment based on a presumptive clinical diagnosis has already been started - the diarrhoea has already improved (self-limiting)Situation in developing countriesLimitations and low availability of laboratory diagnosis are partly behind the rationale for the recommendation (WHO 1995) for treatment of shigellosis and cholera from presumptive diagnoses. Both of these diseases can: · cause complications and death if not treated · be cured by early appropriate antibiotic therapyTable footnotes 1. Treatment should also be given for presumptive clinical diagnoses according to the criteria on screen 33. 2. These antibiotics are not licensed for use in children under the age of 15 years.Image references ################ .\IMAGES\T33962p.jpg Antidiarrhoeal Drugs in the Treatment of Diarrhoea Antidiarrhoeal Drugs in the Treatment of DiarrhoeaImage references ################ Antidiarrhoeal Drugs in the Treatment of Diarrhoea - 1Antimotility drugs in adults How do these drugs work? In adults with acute watery diarrhoea receiving ORT, loperamide causes a significant reduction in:· stool frequency · duration of diarrhoea As an adjunct to rehydration, antimotility drugs may have a limited role in the symptomatic treatment of acute watery diarrhoea in adults. What are the main concerns aboutthese drugs? Picture: Adverse effects of loperamide in adults. These are relatively rare, occurring in less than 1% of patients.Headaches Dizziness Skin reactions, eg. urticariaBloating Abdominal cramps Paralytic ileus Constipation Copyright Image from The Wellcome Trust. How do antimotility drugs work?The common antimotility drugs - loperamide, diphenoxylate-atropine and codeine: · are all opioids · slow down intestinal transit by reducing the release of acetylcholine by enteric nerves - this may reduce fluid losses in the stool · may also have an antisecretory effect on some types of diarrhoeaLoperamide A typical regimen of loperamide hydrochloride in an adult is: 1. 4 mg initially 2. 2 mg after each loose stool for up to 5 days The total dose should not exceed 8 mg/day. Limited role The role of antimotility drugs is limited to adult patients who: · have acute watery diarrhoea · are not seriously ill · are inconvenienced by their diarrhoea, eg. in traveller’s diarrhoeaAcute watery diarrhoeaAntimotility drugs are restricted to acute watery diarrhoea in adults and should never be given to a patient with: · fever · dysentery In invasive diarrhoea (eg. shigellosis), loperamide: · prolongs the fever · increases the time to clear the infection, so prolonging the carriage of pathogens · increases the contact time between bacteria and bowel, so increasing the severity of invasion Concerns about useWHO does not recommend the use of loperamide, even restricted to adults with acute watery diarrhoea. This reflects concerns about: · diverting attention and scarce resources from ORT or appropriate antibiotics · adverse effects (see picture) · possible risks of not eliminating (‘flushing out’) the enteric pathogen Remember that antimotility drugs are contraindicated in: · patients with fever or dysentery · children under 4 years (see screen 39) Image references ################ .\IMAGES\Adult.gif Antidiarrhoeal Drugs in the Treatment of Diarrhoea - 2Antimotility drugs in children In young children with acute watery diarrhoea receiving ORT, antimotility drugs cause: · no significant improvement in the symptoms of diarrhoea · serious adverse effects in some cases (see picture) Antimotility drugs should never be given to a child under 4 years of age.Picture: Adverse effects of antimotility drugs in children. These are relatively common, occurring in up to 20% of patients.Diphenoxylate- atropine Anorexia,nausea,vomitingAbdominal distension, paralytic ileus Loperamide Abdominal distension Enterocolitis,paralytic ileus Skin reactions CNS effects (eg. depressed respiration, convulsions, coma) CNS effects (eg. drowsiness) Copyright Image from The Wellcome Trust.Image references ################ .\IMAGES\Toddler4.gif Antidiarrhoeal Drugs in the Treatment of Diarrhoea - 3Bismuth subsalicylate How does this agent work? In patients with acute watery diarrhoea receiving ORT, bismuth subsalicylate causes a 20 - 30% reduction in the: · total stool output · duration of diarrhoea Bismuth subsalicylate has only a modest impact on acute watery diarrhoea and is not recommended. What are the main concerns aboutthis agent? Picture: Possible modes of action of bismuth subsalicylate. Bismuthsubsalicylate Bismuth oxide Salicylate Antibacterial Inactivation of toxins Anti- secretory effects Copyright Image from The Wellcome Trust. How does bismuth subsalicylate work?Bismuth subsalicylate reacts with hydrochloric acid in the stomach (see picture) to form: · bismuth oxychloride - this is converted to bismuth oxide in the gastrointestinal tract and is not absorbed · salicylate - this is absorbed into the circulation Bismuth subsalicylate is thought to: · have antibacterial effects due to bismuth · reduce attachment of pathogens to the bowel mucosa · inactivate enterotoxins · have antisecretory effects due to salicylate Concerns about useWHO does not recommend the use of bismuth subsalicylate. This reflects concerns about: · diverting attention and scarce resources from ORT or appropriate antibiotics · inconvenience of the treatment regimen - the agent must be taken in large amounts and causes the stools to go black · possible adverse effects, eg: - encephalopathy due to bismuth - Reye’s syndrome in children due to salicylate · uproven efficacy Image references ################ .\IMAGES\Bsubact.gif Antidiarrhoeal Drugs in the Treatment of Diarrhoea - 4Adsorbents How do these agents work? In general these agents cause: · no significant improvement in: - stool output- duration of diarrhoea · minor improvements in stool consistency Adsorbents have no clinically significant impact on diarrhoea and are not recommended. What are the main concerns about these agents? Adsorbents Used in the Treatment of Diarrhoea · Clays Kaolin - with or without pectin Attapulgite Smectite · Activated charcoal · CholestyramineHow do adsorbents work?Adsorbents (see table): · adsorb bacterial toxins (and antibiotics given within 3 hours of the adsorbent) · may coat the bowel mucosa - with unknown effects · may absorb some waterConcerns about useWHO does not recommend the use of adsorbents. This reflects concern about: · diverting attention and scarce resources from ORT or appropriate antibiotics · possible adsorption and inactivation of antibiotics · unproven efficacy Image references ################ What is the role of the following treatments in a patient with acute diarrhoea? Click your mouse on a treatment box below. Hold the mouse down and drag the box to match the correct description of its role.To return to the start of the section. Role in acute diarrhoea Treatment Essential in all patients Indicated for specific enteric infections Limited role in symptomatic treatment of watery diarrhoea Not recommended due to lowefficacy Not recommended due toserious adverse effects Drugs in the Treatment of Diarrhoea: AssessmentAntimicrobials in adults and children Antidiarrhoeal drugs in children Bismuth subsalicylate and adsorbents Prevention or treatmentof dehydration Antimotility drugsin adults Yes. That's right. Yes. That's right. Yes. That's right. Yes. That's right. Yes. That's right. No. That's wrong. Try again. Well done. You have now finished this assessment.Image references ################ Tutorial AssessmentAre the following statements true or false? To return to the start of the tutorial. Click on the True or False button for each statement. 1. Persistent diarrhoea has a particularly large impact on nutritional status.2. All children with diarrhoea and severe malnutrition need intravenous rehydration.3. A patient with a bloody stool should receive prompt treatment for amoebic dysentery.4. Antidiarrhoeal drugs should never be used in children.Correct Although all episodes of diarrhoea can worsen nutritional status, the greatest impact is in a child with: · persistent diarrhoea · recurrent episodes of acute diarrhoeaIncorrect Text 11 pt Arial dark blue goes here Incorrect Although all episodes of diarrhoea can worsen nutritional status, the greatest impact is in a child with: · persistent diarrhoea · recurrent episodes of acute diarrhoeaCorrect Text 11 pt Arial dark blue goes here Correct Text 11 pt Arial dark blue goes here Incorrect In a severely malnourished child, intravenous rehydration is: · potentially dangerous - oral rehydration is much safer · indicated only for hypovolaemic shockIncorrect Text 11 pt Arial dark blue goes here Correct In a severely malnourished child, intravenous rehydration is: · potentially dangerous - oral rehydration is much safer · indicated only for hypovolaemic shockCorrect Text 11 pt Arial dark blue goes here Incorrect Dysentery is an indication for antibiotics against Shigella. Drugs to treat amoebic dysentery are indicated only for: · microscopic detection in the stool of Entamoeba histolytica trophozoites containing red blood cells · failure of two different antibiotics normally effective against ShigellaIncorrect Text 11 pt Arial dark blue goes here Correct Dysentery is an indication for antibiotics against Shigella. Drugs to treat amoebic dysentery are indicated only for: · microscopic detection in the stool of Entamoeba histolytica trophozoites containing red blood cells · failure of two different antibiotics normally effective against ShigellaCorrect Antidiarrhoeal drugs in children with diarrhoea: · have no clinically proven value · are potentially dangerous · divert attention and resources from rehydration and appropriate antibioticsIncorrect Text 11 pt Arial dark blue goes here Incorrect Antidiarrhoeal drugs in children with diarrhoea: · have no clinically proven value · are potentially dangerous · divert attention and resources from rehydration and appropriate antibioticsCorrect Text 11 pt Arial dark blue goes hereImage references ################ Summary Click on the buttons below for summary information. Picture: Assessment of malnutrition in a refugee camp by measuring mid-upper arm circumference.Diarrhoea and Malnutrition Nutrition in the Treatment of Acute Diarrhoea Treatment of Diarrhoea with Severe Malnutrition Antimicrobials in the Treatment of Diarrhoea Antidiarrhoeal Drugs in the Treatment of Diarrhoea Copyright Image from Medicins Sans Frontieres. Diarrhoea and Malnutrition Diarrhoea causes nutritional decline through: · reduced dietary intake · increased metabolism · direct losses · reduced digestion and absorption of nutrients Malnutrition predisposes to diarrhoea of increased: · duration · clinical severity · case fatality rateNutrition in the Treatment of Acute Diarrhoea Breast feeding throughout an episode of acute diarrhoea reduces the: · severity of diarrhoea · duration of diarrhoea In non-breast fed infants with acute diarrhoea: · non-breast milk is rarely associated with lactose intolerance · lactose free formula milk is rarely necessary Restarting complementary feeding after initial rehydration causes: · absorption of significant amounts of nutrients · a reduction in nutritional decline · more rapid recovery of intestinal functionTreatment of Diarrhoea with Severe Malnutrition 1. Management of hypoglycaemia 2. Management of hypothermia 3. Management of dehydration 4. Correction of electrolyte imbalance 5. Prevention or treatment of infection6. Correction of micronutrient deficiency7. Cautious feeding 8. Facilitation of catch-up growth 9. Sensory stimulation 10. Preparation for follow-upAntimicrobials in the Treatment of Diarrhoea The only enteric infections for which antimicrobial treatment is indicated are: · shigellosis· cholera · amoebic dysentery · persistent diarrhoea due to Giardia The choice of antibiotic depends on: · resistance of local strains · availability · costAntidiarrhoeal Drugs in the Treatment of Diarrhoea Antidiarrhoeal drugs: · vary in efficacy - most have little proven benefit · are not generally recommended, especially not in children Antidiarrhoeal drugs include: · antimotility drugs, eg. loperamide· adsorbents, eg. kaolin · antisecretory drugs· other agents, eg. bismuth subsalicylateSection 1 Section 2 Section 3 Section 4 jpg image goes here Copyright Copyright Image from ....... (copyright info) (10 point Arial, blue) Section 1 Pop-up text is in blue with a yellow title in 10 pt bold left aligned.The pop up is a display icon within the library, and if the text is too long then a scroll bar should be used, pop-up boxes can be larger. Section 2 Pop-up text is in blue with a yellow title in 10 pt bold left aligned.The pop up is a display icon within the library, and if the text is too long then a scroll bar should be used, pop-up boxes can be larger. Section 3 Pop-up text is in blue with a yellow title in 10 pt bold left aligned.The pop up is a display icon within the library, and if the text is too long then a scroll bar should be used, pop-up boxes can be larger. Section 4 Pop-up text is in blue with a yellow title in 10 pt bold left aligned.The pop up is a display icon within the library, and if the text is too long then a scroll bar should be used, pop-up boxes can be larger.Image references ################ .\IMAGES\T45861.jpg You have now finished the tutorial The Role of Diet and Drugs ã The Trustee of the Wellcome Trust, 1998 Further reading Further activities Restart tutorial Picture: Trophozoites of G. lamblia shown by light microscopy of a stool sample. Copyright Image from Centers for Disease Control and Prevention. Further reading Brown KH. Dietary management of acute diarrheal disease: contemporary scientific issues. J Nutr 1994;124:1455S-1460S. Golden MHN. Severe malnutrition. In: Weatherall DJ, Ledingham JGG, Warrell DA, eds. Oxford textbook of medicine. Vol. 1. 3rd ed. Oxford, 1995:1278-96. Mata L. Diarrhoeal disease as a cause of malnutrition. Am J Trop Med Hyg 1992(Suppl):16-27. Patwari AK. Multidrug resistant Shigella infections in children. J Diarrhoeal Dis Res 1994;12:182-6. Schiller LR. Anti-diarrhoeal pharmacology and therapeutics. Aliment Pharmacol Ther 1995;9:87-106. World Health Organization. Management of severe malnutrition. A manual for physicians and other senior health workers. WHO: Geneva, 1998. World Health Organization. The treatment of diarrhoea - a manual for physicians and other senior health workers. WHO/CDR/95.3. Geneva: WHO, 1995. World Health Organization. The rational use of drugs in the management of acute diarrhoea in children. Geneva: WHO, 1990.Further activities To look at pictures related to this tutorial, search the image collection using the following keywords: · disease name - other diseases - severe malnutrition · treatment Image references ################ .\IMAGES\T33307.jpg