Overviewã The Trustee of the Wellcome Trust 1998Reviewed by: Dr A Ashworth, London School of Hygiene and Tropical Medicine,Dr R H Behrens, Hospital for Tropical Diseases, London, ProfessorI W Booth, Institute of Child Health, The University of Birmingham and Dr W A M Cutting, Department of Child Life and Health, The University of Edinburgh, UKPicture: Campylobacter jejuni, an important cause of watery and bloody diarrhoea.Copyright Image from Skirrow MB courtesy of Purdham DR.Image references ################ .\IMAGES\T45525a.jpg Contents Screen3Objectives 4 Introduction 5 Epidemiology 11 Assessment 12 Prevention and Control 18 Assessment 19 Principles of Case Management 25 Assessment 26 Acute Watery Diarrhoea 30 Assessment 31 Acute Bloody Diarrhoea 35 Assessment 36 Persistent Diarrhoea including Severe Malnutrition 41 Assessment 42 Defence Mechanisms 48 Assessment49Summary Click on the underlined text to jump tothat screen. Picture: A child before (left) and after (right) persistent diarrhoea. Underlined text is interactive. Click on underlined text to view extra information or to jump to another screen. Copyright Copyright Images from Behrens RH.Image references ################ .\IMAGES\T45345c.jpg ObjectivesAt the end of this tutorial you should be able to: 1. define diarrhoea, its clinical types, aetiology and global impact2. describe the risk factors associated with the transmission of diarrhoea 3. list the interventions that aim to prevent or control diarrhoea and how they work 4. review the principles of clinical assessment and treatment of a patient with diarrhoea 5. summarize the management of acute watery diarrhoea, dysentery and persistent diarrhoea, including severe malnutrition 6. outline gastrointestinal defence mechanisms and mucosal vaccines 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 gives an overview of diarrhoeal diseases in developing countries. Picture: Intravenous rehydration for severe dehydration due to diarrhoea. A needle is being inserted into this child’s scalp vein. Copyright Image from Cutting WAM. Diarrhoea morbidity and mortalityEach 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\T23740.jpg EpidemiologyEpidemiology Image references ################ Epidemiology - 1Clinical typeDefinition Acute wateryLoose or watery stools without visible blood diarrhoea Duration less than 14 days1 Acute bloodyLoose or watery stools with visible red blood2 diarrhoea Duration less than 14 days1PersistentLoose or watery stools with or without visible diarrhoea blood Duration 14 days or more 1.Most episodes of acute diarrhoea last less than 5 - 7 days. 2.A history of bloody stools reported by the mother is sufficient for a diagnosis. Clinical Types of Infectious Diarrhoea Definition of diarrhoea Diarrhoea is defined as the passage of stools that are both: 1. loose or watery2. frequent, ie. three or more stools in24 hours Who is not included in this definition? Infectious diarrhoea presents as three clinical syndromes (see table).Loose or watery stoolPicture: A watery stool from a patient with diarrhoea due to enterotoxigenic Escherichia coli. Image from Tubbs HR.A loose stool is defined as one that takes on the shape of the container into which it is passed.Not included in the definitionThe definition does not apply to babies in whom breast milk is a major component of their diet.These babies: · often pass more than three soft stools each day even when healthy · are defined as having diarrhoea when the mother notices that the stools are more frequent or watery Image references ################ .\IMAGES\T22792p.jpg Epidemiology - 2 Episodes DeathsDiarrhoea morbidity and mortality In developing countries, it is estimated that each year there are: · over 1 billion episodes of diarrhoea in children· an average of 2.6 diarrhoea episodes per child· 3.3 million deaths from diarrhoea, 80% occurring in the first 2 years of life Pie charts: Annual numbers of episodes of diarrhoea and deaths from diarrhoea worldwide. Data from WHO 1995 and Bern et al 1992. Click on each part of the lower pie chart for details. 200 million200 million1.4 billion1.2 million480,0001.6 millionAcute wateryAcute bloody Persistent Copyright Image from The Wellcome Trust modified from Bern C et al. Bull World Health Organ 1992;70:705-14 and World Health Organization. The World Health Report 1995. Geneva: WHO, 1995. Diarrhoea in childrenGraph: Morbidity for children under 5 years in developing countries. Image from The Wellcome Trust modified from Snyder JD, Merson MH. Bull World Health Organ 1982;60:605-13. Diarrhoea episodes/child/year 3210 The peak incidence occurs at around 6 - 12 months. This largely reflects the introduction of contaminated weaning foods. 0-56-11 12-23 24-35 36-47 48-59 Age (months) Deaths from diarrhoeaThe data shown probably underestimate the mortality due to persistent diarrhoea, which recent studies suggest causes 45% of all diarrhoea deaths.Diarrhoea episodesIn some highly contaminated environments, such as shanty towns, children can have up to 10 episodes of diarrhoea each year. Refer to the tutorial Diarrhoeal Diseases: Epidemiology.Acute bloody diarrhoeaAcute bloody diarrhoea (dysentery): · can cause extraintestinal complications (eg. haemolytic-uraemic syndrome) and malnutrition · is caused mainly by: - Shigella - Campylobacter jejuni - non-typhoid Salmonella - Entamoeba histolytica (in adults) Refer to the tutorial Diarrhoeal Diseases: Acute Bloody Diarrhoea.Acute watery diarrhoeaAcute watery diarrhoea: · can rapidly cause dehydration · is caused mainly by: - rotavirus - enterotoxigenic E. coli (ETEC) - Vibrio cholerae O1 Refer to the tutorial Diarrhoeal Diseases: Acute Watery Diarrhoea.Persistent diarrhoeaPersistent diarrhoea is: · very closely linked to malnutrition (persistent diarrhoea-malnutrition syndrome) · often associated with non-intestinal infections, eg. pneumonia · caused by pathogens similar to those of acute diarrhoea, but especially with: - enteroaggregative E. coli- Cryptosporidium - Shigella - Giardia lamblia Refer to the tutorial Diarrhoeal Diseases: Persistent Diarrhoea. Image references ################ .\IMAGES\Diapies.gif .\IMAGES\Diarincp.gif Epidemiology - 3 Food Drinking water Person to person Faecal-oral transmission Diarrhoea pathogens are generally spread by faecal-oral transmission (see picture) through: · contamination of food · faecal contamination of drinking water · direct person to person spread Are any other modes of transmissionseen? Picture: Modes of faecal-oral transmission. For related tutorials.Faecal contaminationof hands and clothes Contaminated with faeces Endogenous pathogens Contact, fingers putin mouth Not cooked thoroughly Copyright Image from The Wellcome Trust. Contamination of foodFood can come to contain pathogens through two main routes. These are: · contamination with faeces containing diarrhoea organisms · natural contamination by organisms infecting animals used as human food Contaminated food is important in the transmission of: · V. cholerae O1, eg. seafood, vegetables · C. jejuni, eg. chicken and pork · non-typhoid Salmonella, eg. poultry and eggs · enterohaemorrhagic E. coli, eg. beefburgersContamination of waterWater becomes contaminated with faeces containing diarrhoea organisms through: · defaecation into or near a water source, eg. a river · rainwater washing faeces into a water source, eg. an unprotected well · a dirty hand or utensil put into stored domestic water Contaminated water is important in the transmission of: · V. cholerae O1 · Cryptosporidium · Giardia lamblia Person to person spreadPerson to person contact involves faecal contamination of: · hands · clothes · fomites, eg. a towel Person to person contact is important in the transmission of: · Shigella · rotavirus · Entamoeba histolyticaRelated tutorials Refer to the tutorial Diarrhoeal Diseases: Epidemiology.Other modes of transmissionPicture: Rotavirus particles.Image from Centers for Disease Control and Prevention. There is now reasonably good evidence that rotavirus (see picture) can be transmitted from person to person via the aerosol route. Image references ################ .\IMAGES\Foraltsm.gif .\IMAGES\T33755p.jpg Epidemiology - 4Risk factors for diarrhoea Diarrhoea is associated with: · failure to breast feed · impaired immunity· malnutrition· lack of food hygiene· poor weaning practice· lack of sufficient clean water · inadequate sanitation · poor personal and domestic hygienePicture: A slum in Calcutta, India, where conditions favour the transmission of diarrhoea. Diarrhoea is often a disease of low socioeconomic status affecting mostly children in developing countries, poorer communities and low income households.Copyright Image from Tomkins AM. Failure to breast feedGraph: The effect of breast feeding on the incidence of diarrhoea. The relative risks compare no breast feeding with exclusive or partial breast feeding. Image from The Wellcome Trust modified from Feachem RG, Koblinsky M. Bull World Health Organ 1984;62: 271-91.Relative risk 3 2 10-33-56-99-11 Age (months) Failure to breast feed greatly increases the risk in infancy of: · morbidity due to diarrhoea (see graph) · severe diarrhoea · death due to diarrhoeaImpaired immunityFactors that predispose to diarrhoea by impairing defence mechanisms include: · measles · malnutrition, particularly severe malnutrition · micronutrient deficiency, eg. of vitamin A and zinc · concurrent infections, eg. pneumonia · human immunodeficiency virus (HIV) infectionMalnutrition Malnutrition, particularly severe malnutrition, predisposes to diarrhoea of increased: · duration · severity, ie. stool frequency or volume · case fatality rate Refer to the Diarrhoeal Diseases tutorials: · Epidemiology · The Role of Diet and Drugs Poor weaning practiceTransmission of diarrhoea is favoured by: · faecal contamination of weaning foods and liquids · introducing complementary foods too early (before4 months of age) or too late (after 6 months) · giving weaning foods of low energy and nutrient content · weaning abruptly Image references ################ .\IMAGES\T25658.jpg .\IMAGES\Brstfedp.gif Epidemiology - 5Diarrhoea and malnutrition Diarrhoea causes nutritional decline through: · reduced dietary intake· increased metabolic rate · direct losses from the bowel · reduced digestion and absorption of nutrients Pre-existing malnutrition increases the: · duration, severity and case fatality rate of diarrhoea · incidence of persistent diarrhoea and possibly of acute diarrhoea Diarrhoea Impaired defence mechanisms Reduced intake and absorption of nutrients Malnutrition Picture: The vicious circle of diarrhoea and malnutrition. Diarrhoea causes malnutrition and malnutrition predisposes to diarrhoea. Copyright Image from The Wellcome Trust. Vicious circleThe link between diarrhoea and malnutrition is so close that diarrhoea can be considered as a ‘nutritional’ disease as much as one of fluid and electrolyte loss.Diarrhoea causes malnutritionPicture: ABangladeshi child with persistent diarrhoea-malnutrition syndrome. Image from Behrens RH.The impact of diarrhoea on nutritional status is greatest for: · persistent diarrhoea (see picture) · recurrent episodes of acute diarrhoeaReduced dietary intakeDiarrhoea causes reduced intake of food through: · anorexia · dilution of the child’s usual food by the carer · withholding of solid food completely by the carer Refer to the tutorial Diarrhoeal Diseases: The Role of Diet and Drugs.Increased diarrhoea incidence Malnutrition predisposes to diarrhoea because it impairs defence mechanisms such as: · cell-mediated immunity · production of IgA (see screen 44) · intestinal secretions, eg. gastric acid · integrity of the bowel mucosa Image references ################ .\IMAGES\Circdia2.gif .\IMAGES\T45355p.jpg For each of the pictures shown, think of three or four factors that are often associated with the transmission of diarrhoea.Click on each picture for our answers. To return to the start of the section. Epidemiology: AssessmentSlum Nigerian childCopyright Image from United Nations Children's Fund, India. Copyright Image from WHO Photo Library courtesy of Lejneu A. Answer: Slum environmentFactors associated with diarrhoea in this setting include: · lack of sufficient clean water · inadequate sanitation causing environmental contamination with faeces · lack of food hygiene· poor domestic hygiene · overcrowdingAnswer: Nigerian child Factors associated with diarrhoea in children include: · failure to breast feed · impaired immunity, eg. due to measles or HIV infection · malnutrition and micronutrient deficiency · poor weaning practice · poor personal hygiene Image references ################ .\IMAGES\T23718s.jpg .\IMAGES\T34919s.jpg Prevention and ControlPrevention and Control Image references ################ Prevention and Control - 1 Interventions for the Prevention and Control of Diarrhoea Maternal and child health 1. Promotion of breast feeding 2. Improvement of weaning practices 3. Vitamin A supplementation Immunization 4. Vaccination against rotavirus, cholera and measlesInterrupting transmission 5. Improvement of water supply and sanitation 6. Promotion of personal and domestic hygiene Case management 7. Improvement of the treatment of diarrhoeaInterventions Interventions to reduce diarrhoea morbidity and mortality (see table) have been selected for their: · effectiveness · feasibility · cost-effectiveness What is the role of health promotion in diarrhoea preventionand control?EffectivenessThe effectiveness of an intervention is the extent to which it reduces diarrhoea: · incidence · severity · mortality Refer to the tutorial Diarrhoeal Diseases: Prevention and Control.Cost-effectivenessThe cost-effectiveness of an intervention is the cost of averting each: · episode of diarrhoea · death due to diarrhoeaHealth promotionWhere implementing an intervention requires behavioural changes, this is facilitated by health promotion. Methods include: · face to face communication · distribution of leaflets and posters· broadcasts by radio and other mass media Messages can be promoted at: · antenatal and postnatal clinics · growth monitoring visits · oral rehydration or nutrition clinics Image references ################ Prevention and Control - 2For picture legend. Maternal and child health Exclusive breast feeding is promoted through: · breast feeding counsellors · changing hospital practice Which advantages of breast feeding should be promoted? Weaning practices that should be promoted are improved: · food hygiene · nutrition Prophylactic vitamin A supplementation: · reduces diarrhoea mortality in young children by 30% · has no significant impact on diarrhoea incidenceCopyright Image from J Ebrahim Memorial Trust. Picture legend Picture. Breast feeding in hospital after delivery. WHO policy is to promote exclusive breast feeding for the first 4 - 6 months of life, then breast feeding with complementary feeding up to age at least 2 years.Breast feeding counsellorsBreast feeding counsellors provide mothers with information and support at: · antenatal and postnatal clinics · delivery · home visits Other means of promoting breast feeding include: · leaflets and posters · mass media campaigns · the International Code of Marketing of Breast-milk Substitutes Improved weaning food hygienePractices that should be promoted include: · washing hands before preparing or giving food · using boiling water to prepare formula milk · not leaving cooked food for a long time at room temperature · feeding gruels using a clean cup and spoon Improved weaning nutritionPicture: A young Indian girl (arrow) with severe malnutrition who was weaned abruptly when the mother became pregnant again. The younger child is being breast fed and is healthy. Image from Cutting WAM. Practices that should be promoted include: · introducing complementary foods between 4 and 6 months of age · giving food of high energy and nutrient concentration · completing weaning gradually not abruptly (see picture)Changing hospital practiceHospital practice can be changed through the Baby Friendly Hospital Initiative. Key aspects include: · informing all mothers about the benefits of breast feeding · helping mothers to start breast feeding soon after delivery (see picture) · practising rooming in, ie. mothers sleeping in the same room as their babies · encouraging breast feeding on demand · discouraging the use of pacifiers For more details refer to the tutorial Diarrhoeal Diseases: Prevention and Control.Advantages of breast feedingBreast feeding can be promoted to mothers because it: · helps the child to grow and stay healthy · protects from diarrhoea and other infections · provides the ideal complete food for the baby’s first 4 - 6 months · is convenient and cheap · helps with birth spacing · encourages emotional bonding between mother and baby Image references ################ .\IMAGES\T37730.jpg .\IMAGES\T23661p.jpg Prevention and Control - 3Immunization Vaccines that reduce diarrhoea morbidity or mortality are targeted at: · rotavirus · cholera · measles (see picture) Picture: Vaccination for measles in Rwanda. Under the EPI, measles immunization in developing countries is given as a single dose at the age of9 months. Why is measles so important indiarrhoea control? Copyright Copyright holder unknown. Image supplied by MERLIN picture library. Measles vaccine Immunization with a live attenuated measles vaccine: · is an integral part of the WHO Expanded Programme on Immunization (EPI) · has an efficacy of over 85% against measles transmission and mortality · significantly reduces the: - incidence of diarrhoea - diarrhoea mortality rate Measles vaccination Note that the recommended site for intramuscular injection of the vaccine is the lateral thigh. Rotavirus vaccineThe most advanced of the current oral rotavirus vaccines under development: · has an efficacy against rotaviral diarrhoea of approximately: - 45% for any episode - 70% for severe dehydrating diarrhoea · offers no protection against infection with rotavirus · may soon be incorporated into existing immunization programmes Cholera vaccinesTwo types of oral vaccine against V. cholerae O1 have been licensed (see screen 46). Versions of the killed whole cell vaccine: · have an efficacy against endemic cholera of approximately: - 45% in children - 65% in adults · are unlikely to be incorporated into existing immunization programmes because of their low cost-effectivenessImportance of measlesPicture: A child with severe measles receiving nasogastric fluids for dehydration due to diarrhoea. Image from Rolfe M.Measles is: · often accompanied by diarrhoea · a risk factor for subsequent severe or persistent diarrhoea · a major cause of death and disability in its own right Image references ################ .\IMAGES\T45823.jpg .\IMAGES\T18168p.jpg Prevention and Control - 4 Air currents Flies Interrupting transmission The transmission of diarrhoea is often reduced by improvements in: · water supply · sanitation (see picture)· personal and domestic hygiene How effective are such measures? How do these improvements impact on diseases other than diarrhoea?Screen Air currents Vent Pit Flies Faeces Picture: The structure of a ventilated improved pit latrine.Copyright Image from The Wellcome Trust. Improvements in water supplyPicture: A child being taught to wash her hands. Copyright holder unknown.Image from World Neighbours.In: Diarrhoea, a major public health problem.Save the Children Fund.Improved water supply (eg. a communal tap, or clean water piped into the home) reduces diarrhoea incidence and mortality by: · reducing the ingestion of contaminated drinking water · facilitating personal and domestic hygiene (see picture)Improvements in sanitationPicture: A pit latrine in Zimbabwe. Image from Furu P.Improved sanitation (eg. a pit latrine or flush toilet) reduces diarrhoea incidence and mortality by permitting hygienic disposal of faeces. This reduces contamination of: · sources of drinking water · the domestic and general environmentImprovements in personal and domestic hygieneHealth promotion programmes aim to encourage: · hand washing · sanitary disposal of faeces · maintaining drinking water free from faecal contamination For more details refer to the tutorial Diarrhoeal Diseases: Prevention and Control.EffectivenessThe impact of water supply or sanitation on diarrhoea varies greatly. Effectiveness depends on the: · level of water supply or sanitation present before the intervention · type of facility being installed · patterns of breast feeding and infant nutrition · patterns of hygiene behaviour · aetiology of diarrhoeaImpact on other diseasesImprovements in water supply and sanitation may also reduce the incidence of diseases other than diarrhoea. For example: · ascariasis · dracunculiasis · ancylostomiasis · schistosomiasis · trachoma Image references ################ .\IMAGES\Viplatr.gif .\IMAGES\T23793p.jpg .\IMAGES\T28486p.jpg Prevention and Control - 5Use of ORS solution and drugs, including antibiotics and antidiarrhoeal agents, in children under 5 with acute diarrhoea. Case management Effective diarrhoea case management requires promotion of: · treatment of dehydration, eg. oral rehydration therapy (ORT) · appropriate nutritional management (see screen 23) · rational use of antibiotics and other drugs · treatment of associated infections or complications For related tutorials. % 60 50 40 30 20 10 0 Data from WHO 1989. ORT use Drug use AfricaSouthSoutheastEasternWestern AmericaAsia Med. Pacific Copyright Image from The Wellcome Trust modified from World Health Organization. CDD Programme. Geneva: WHO, 1989. Promotion of ORTORT: · has been proven to reduce deaths from diarrhoeal dehydration · has no impact on the stool output or duration of diarrhoea · is often not used at all, or used in insufficient volume More widespread and effective rehydration requires that: · ORT is promoted at all levels of healthcare · oral rehydration salts (ORS) are subject to social marketing · health workers reinforce correct practice Rational use of drugsPoor case management in developing countries includes the widespread prescription (see graph) of: · antibiotics - these are indicated only for specific enteric infections · antidiarrhoeal drugs - these should never be given to a child with diarrhoea More rational drug use is promoted by: · training doctors, health workers and pharmacists · increasing public understanding that not all diarrhoea requires drugs · legislation to withdraw inappropriate preparations from the marketplace Related tutorialsRefer to the Diarrhoeal Diseases tutorials: · Prevention and Control · Rehydration and Early Feeding · The Role of Diet and Drugs Antidiarrhoeal agentsThe most widely misused antidiarrhoeal agent is the antimotility drug loperamide (see screen 24). In young children, loperamide has: · no proven efficacy · a range of dangerous adverse effects Image references ################ .\IMAGES\Druguse.gif To return to the start of the section. How do interventions to prevent diarrhoea work?Click your mouse on an intervention.Hold the mouse down and drag the box to match the correct mechanism. Increased resistance to diarrhoea and reducedexposure to diarrhoea pathogens Increased resistance to diarrhoea Reduced exposure to diarrhoea pathogens Prevention and Control: AssessmentRotavirus vaccination Improved water supply and sanitation Breast feeding 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 ################ Principles of Case ManagementPrinciples of Case Management Image references ################ Principles of Case Management - 1 Clinical assessment Examination of a child with diarrhoea aims to determine: · the degree of dehydration· the clinical type of diarrhoea (see screen 6) · nutritional status and feeding practices· whether the child has any concurrent illness · immunization status, especially with regard to measles How important arelaboratory investigations?Video: A skin pinch being performed to assess the degree of dehydration. The very slow return of the skin pinch indicates severe dehydration.How else is the degree of dehydration assessed? To run the video. Copyright Image and video from United Nations Children's Fund, India. Assessment of dehydrationThe degree of dehydration is assessed by physical examination using a standardized WHO chart of clinical signs. Examination is made of the patient’s: · skin turgor (see video) · general condition and behaviour · eyes · tears · mouth and tongue · thirst Role of laboratory investigationsLaboratory diagnosis of the causative enteric pathogen: · is not usually necessary for treatment · may take several days, whereas treatment must be started immediately · often requires resources that are not available Where available, techniques to support the clinical assessment include: · stool microscopy for parasites, eg. Entamoeba histolytica and Giardia lamblia · stool culture for bacterial pathogens, eg. Shigella and V. cholerae O1 · immunological and nucleic acid based methods Degree of dehydrationClinical assessment should establish the degree of water and electrolyte loss as: · no signs of dehydration - treat with home available fluids· some dehydration - treat with ORT · severe dehydration - treat with urgent intravenous rehydration Refer to the tutorial Diarrhoeal Diseases: Clinical Assessment. Nutritional statusKey aspects of the assessment of nutritional status are: ·diagnosis of severe malnutrition and vitamin deficiency, eg. vitamin A · anthropometry (eg. weight for height) and use of growth curvesConcurrent illnessesCommon illnesses in children with diarrhoea are: · acute respiratory infection, eg. pneumonia · malnutrition· malaria· measles· septicaemia · urinary tract infection · otitis media Image references ################ .\IMAGES\Diarrh4.jpg Principles of Case Management - 2Overview of treatment In a child with diarrhoea of any type, the key steps in treatment are: · prevention or treatment of dehydration · appropriate nutritional management· giving antimicrobials for specific enteric infections (see screen 24) · treatment of associated infections or complications Are these measures always equally important?Picture: Breast feeding in an oral rehydration clinic. Breast feeding should be continued throughout diarrhoea because it reduces the severity and duration of the episode. 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. Nutritional management Appropriate nutrition during the episode includes: · continuing breast feeding (see picture) · early restarting of complementary food · defined diets and micronutrient supplementation for persistent diarrhoea Importance of treatment measuresAll the measures listed must be addressed in all patients with diarrhoea, although the relative importance of each measure will vary. For example: · rehydration is often the priority in a patient with acute watery diarrhoea · antibiotic treatment is particularly important in a patient with dysentery · nutritional management is central to the treatment of persistent diarrhoea Image references ################ .\IMAGES\T45262.jpg Principles of Case Management - 3Prevention or treatment of dehydration Treatment differs for children with: · no signs of dehydration · some dehydration (see picture) · severe dehydration Picture: A mother giving her child ORS solution by cup and spoon. Older children and adults should take frequent sips from a cup. What is the basis for ORT? Copyright Image from Cutting WAM. No signs of dehydrationThese children need home therapy to prevent dehydration and malnutrition. Mothers should be taught to follow three rules. 1. Give the child more home available fluids than usual, including salted and unsalted drinks, to prevent dehydration. 2. Continue to feed the child as normal, including breast feeding, to prevent malnutrition. 3. Take the child to a health worker if signs of dehydration or other complications appear, eg. fever or bloody stool. Some dehydrationThese children need ORT with ORS solution. Health workers should be able to: · prepare ORS solution from a sachet · show the mother how to give ORT · monitor the child’s rehydration · instruct the mother about continuing treatment at home Standard ORS solution does not reduce the stool output or duration of diarrhoea. Two modifications of the standard solution partly overcome these problems: · cereal based ORS solution · reduced osmolarity glucose based ORS solutionSevere dehydrationThese children need urgent intravenous rehydration in a hospital or health centre with: · Ringer’s lactate, with or without 5% dextrose · normal (0.9%) saline It is important to: · use sterile technique and equipment · record the volume of fluid given · monitor progress, eg. pulse rate Refer to the tutorial Diarrhoeal Diseases: Rehydration and Early Feeding. Basis for ORTORS solution is effective in replacing water and electrolyte losses due to diarrhoea. It works because: · coupled uptake of Na+ and glucose favours the uptake of water and other electrolytes · the Na+, K+ and Cl- content replace losses of these electrolytes in the stool · citrate helps correct acidosis Refer to the tutorial Diarrhoeal Diseases: Organisms and Pathophysiology. Image references ################ .\IMAGES\T44894.jpg Principles of Case Management - 4Feeding in acute diarrhoea During an episode of diarrhoea: · breast feeding should be continued · non-breast milk and complementary foods should be restarted after initial ORT How often should food be given? After an episode of diarrhoea, an extra meal should be given daily for at least 2 weeks to promote catch-up growth. Picture: Foods suitable for a child with acute diarrhoea include cereals and vegetables. These must be prepared properly for feeding to small children. Copyright Image from Chitrabani Society. Breast feeding during diarrhoeaClinical trials show that breast feeding throughout acute or persistent diarrhoea reduces the: · stool volume · stool frequency · duration of diarrhoea Refer to the tutorial Diarrhoeal Diseases: The Role of Diet and Drugs.Non-breast milk during diarrhoeaClinical trials in children with acute diarrhoea show that: · animal milk or formula milk is rarely associated with lactose intolerance · lactose free formula milk is rarely necessary More children with persistent diarrhoea than acute diarrhoea have lactose intolerance. They may need: 1. yogurt, which contains less lactose than animal or formula milk 2. lactose free formula milkComplementary foods during diarrhoeaPicture: Feeding after initial rehydration for acute diarrhoea.Image from United Nations Children's Fund, India. Clinical trials show that restarting complementary feeding after 4 - 6 hours of ORT causes: · absorption of significant amounts of nutrients · a reduction in nutritional decline · more rapid recovery of intestinal function 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 Refer to the tutorial Diarrhoeal Diseases: Rehydration and Early Feeding. Image references ################ .\IMAGES\T25662.jpg .\IMAGES\T45964p.jpg Principles of Case Management - 5Antimicrobial treatment Antimicrobials against enteric pathogens should be given only for:· shigellosis · cholera · amoebic dysentery · persistent diarrhoea due to Giardia (see picture) What are the indications for treatment in each case? Antidiarrhoeal agents These should never be given to a child with diarrhoea.Picture: A Giardia lamblia cyst in a stool specimen. In a patient with persistent diarrhoea, this finding is an indication for giving treatment with metronidazole.Copyright Image from Centers for Disease Control and Prevention. AntimicrobialsAn effective antimicrobial given promptly: · cures the enteric infection causing the diarrhoea · reduces the duration and severity of diarrhoea · is not an alternative to rehydration with early feedingAntidiarrhoeal agents in childrenAntidiarrhoeal agents include: · antimotility drugs, eg. loperamide· adsorbents, eg. kaolin · antisecretory drugs· miscellaneous agents, eg. bismuth subsalicylate These agents: · vary in efficacy - most have no proven value · can be dangerous or even fatal in children Refer to the tutorial Diarrhoeal Diseases: The Role of Diet and Drugs.Indications for Antimicrobials (WHO 1995)DiagnosisIndicationShigellosis 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 Entamoebahistolytica trophozoites containing red blood cells Giardiasis Microscopic detection in the stool of Giardia lamblia cysts or trophozoites in a patient with persistent diarrhoea1. These are the criteria for a 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. Amoebic dysentery can also be diagnosed if two different antibiotics normally effective against Shigella have failed. Image references ################ .\IMAGES\T33312.jpg Principles of Case Management: AssessmentAre the following statements about the management of a child with diarrhoea true or false?To return to the start of the section. Click on the True or False button for each statement. 1. Treatment is based on the clinical type of diarrhoea without the need for laboratory diagnosis.2. The degree of dehydration should be assessed as mild, moderate or severe.3. Breast feeding should be continued throughout the diarrhoea episode.4. All children with diarrhoea should be given antibiotics.Correct Treatment follows from the clinical diagnosis of: · acute watery diarrhoea · acute bloody diarrhoea · persistent diarrhoea Laboratory diagnosis of the causative pathogen has only a limited role in treatment.Incorrect Text 11 pt Arial dark blue goes here Incorrect Treatment follows from the clinical diagnosis of: · acute watery diarrhoea · acute bloody diarrhoea · persistent diarrhoea Laboratory diagnosis of the causative pathogen has only a limited role in treatment.Correct Text 11 pt Arial dark blue goes here Correct Text 11 pt Arial dark blue goes here Incorrect Clinical assessment should establish the degree of dehydration as one of: · no signs of dehydration· some dehydration · severe dehydrationThese categories replace the previous system of classifying dehydration.Incorrect Text 11 pt Arial dark blue goes here Correct Clinical assessment should establish the degree of dehydration as one of: · no signs of dehydration· some dehydration · severe dehydrationThese categories replace the previous system of classifying dehydration.Correct Breast feeding reduces the duration and severity of diarrhoea. Feeding with complementary foods should begin after 4 - 6 hours of ORT.Incorrect Text explaining the answer (11-pt plain blue) Incorrect Breast feeding reduces the duration and severity of diarrhoea. Feeding with complementary foods should begin after 4 - 6 hours of ORT.Correct Text explaining the answer (11-pt plain blue) Correct Incorrect Appropriate antimicrobials should be given only for: · shigellosis · cholera · amoebic dysentery · persistent diarrhoea due to GiardiaIncorrect Text explaining the answer (11-pt plain blue) Correct Appropriate antimicrobials should be given only for: · shigellosis · cholera · amoebic dysentery · persistent diarrhoea due to Giardia Image references ################ Acute Watery DiarrhoeaAcute Watery Diarrhoea Image references ################ Acute Watery Diarrhoea - 1Rotavirus V. cholerae O1 Aetiology The most important causes of acute watery diarrhoea worldwide are: · rotavirus* · enterotoxigenic E. coli (ETEC)* · Vibrio cholerae O1 *These pathogens cause more than half of all the episodes of acute watery diarrhoea in children. Picture: Click on each pathogen for a summary of how it causes diarrhoea. Which other pathogens cause acutewatery diarrhoea? Copyright Image from Centers for Disease Control and Prevention. Copyright Image from The Wellcome Trust. Rotavirus Rotaviral diarrhoea: · is the most important form of severe watery diarrhoea in children under 2 years of age · is important in developed and developing countries · occurs as a ‘winter epidemic’ in temperate countries ETECDiarrhoea due to ETEC: · is important mainly in children, but also in adults, in developing countries· peaks in the warm season · causes more deaths worldwide than cholera · is the most common cause of traveller’s diarrhoeaV. cholerae O1Endemic cholera ( )Image from WHO. WeeklyEpidemiol Record 1997;72:229-36.Endemic cholera: · is important in many developing countries (see map) · peaks in the warm season · affects mainly children aged 2 - 5 years Epidemic cholera: · affects adults and children · can spread rapidly.Pathophysiology of choleraV. cholerae O1 causes acute watery diarrhoea by the following mechanism. 1. The bacterium secretes cholera toxin, which is taken up by the enterocyte. 2. The toxin causes activation of adenylate cyclase, increasing intracellular cAMP levels. 3. Massive secretion of electrolytes and water results. The pathophysiology of ETEC is very similar. It secretes heat labile enterotoxin instead of cholera toxin. Refer to the tutorial Diarrhoeal Diseases: Organisms and Pathophysiology. Pathophysiology of rotaviral diarrhoeaRotavirus causes acute watery diarrhoea by the following mechanism. 1. The virus invades and damages enterocytes in the small bowel. 2. Viral multiplication causes increased enterocyte shedding and proliferation. 3. Reduced absorption is due to repopulating crypt-like enterocytes and stunted villi. Refer to the tutorial Diarrhoeal Diseases: Organisms and Pathophysiology.Other causes of acute watery diarrhoeaOther causes of acute watery diarrhoea include: · viruses: - small round structured viruses, eg. Norwalk agent- enteric adenoviruses· bacteria: - Shigella* - Campylobacter jejuni*- non-typhoid Salmonella*- enteropathogenic E. coli· protozoa: Cryptosporidium *These bacteria can also cause acute bloody diarrhoea. Image references ################ .\IMAGES\1368c.jpg .\IMAGES\Endchol.gif Acute Watery Diarrhoea - 2 Clinical features Clinical features of acute watery diarrhoea include: · watery stools - from loose to extremely high volume· dehydration - severe in some cases (see picture) · vomiting · abdominal cramps · fever in some cases How is a clinical diagnosis of cholera made? Picture: An Egyptian child with severe dehydration due to acute watery diarrhoea.Copyright Copyright holder unknown. Image supplied by Cutting WAM. Watery stoolsPicture: The characteristic ‘rice water’ cholera stool contains flecks of mucus, is pale grey in colour and smells slightly fishy.Image from Behrens RH. In patients with cholera: · stools have a characteristic ‘rice water’ appearance (see picture) · fluid losses from diarrhoea and vomiting can rapidly lead to severe dehydration and deathClinical diagnosis of choleraPicture: An adult with severe dehydration due to cholera. Note the sunken eyes. Image from Bryceson ADM.It is important to diagnose cholera so that antibiotic treatment can be given. Cholera is diagnosed clinically when: · a child aged over 5 years or an adult with acute watery diarrhoea develops severe dehydration· anyone aged over 2 years develops acute watery diarrhoea during a cholera outbreak Image references ################ .\IMAGES\T22303.jpg .\IMAGES\T45352p.jpg .\IMAGES\T39750p.jpg Acute Watery Diarrhoea - 3Treatment The key aspects of treatment of acute watery diarrhoea are: · prevention or treatment of dehydration (see picture) · continued breast feeding and early refeeding of solid food (see screen 23) · giving oral antibiotics for suspected choleraPicture: Intravenous rehydration into the forearm. Patients with severe dehydration need rapid infusion of fluids.Copyright Image from Bryceson ADM. Antibiotics for choleraPreferred antibiotics are: · doxycycline - licensed only for children over 12 years of age · tetracycline · trimethoprim-sulphamethoxazole Alternative antibiotics are: · erythromycin · furazolidone - the antibiotic of choice in pregnancy For details of doses refer to the tutorial Diarrhoeal Diseases: Acute Watery Diarrhoea. Image references ################ .\IMAGES\T39734.jpg Acute Watery Diarrhoea: AssessmentA young woman presents with high volume acute watery diarrhoea and vomiting. She is lethargic with deeply sunken eyes. A skin pinch test returns only very slowly. What is your assessment of her condition? For the answer. What is your immediate priority for treatment? For the answer. Would you give antibiotics, and if so which? For the answer. To return to the start of the section. Answer: Assessment of her conditionThe woman has the following signs of severe dehydration: · lethargy · very sunken eyes · very poor skin turgor Severe dehydration in an adult with acute watery diarrhoea suggests cholera. The vomiting is consistent with this diagnosis.Answer: Priority for treatmentThe immediate risk is death from severe dehydration. The first priority is therefore intravenous rehydration.Answer: AntibioticsAntibiotics are indicated for cholera. The preferred drugs are: · doxycycline · tetracycline · trimethoprim-sulphamethoxazole The choice will reflect the availability of drugs and local patterns of antibiotic resistance. Image references ################ Acute Bloody DiarrhoeaAcute Bloody Diarrhoea Image references ################ Acute Bloody Diarrhoea - 1Aetiology The most important causes of acute bloody diarrhoea worldwide are: · Shigella· Campylobacter jejuni· non-typhoid Salmonella*· enteroinvasive E. coli* · Entamoeba histolytica* *These are much less important pathogens. For details of the pathology of dysentery.Picture: The colon of a Rhesus monkey with shigellosis. Invasive bacteria such as Shigella cause extensive damage to the bowel with mucosal inflammation and ulceration, and production of a mucopurulent exudate.Copyright Image from Centers for Disease Control and Prevention. ShigellaEndemic shigellosis: · is most often due to S. flexneri · is important in many developing countries · causes over 50% of all episodes of bloody diarrhoea · affects mainly children aged 6 months to 3 years · peaks in the warm season Epidemic shigellosis: · is usually due to S. dysenteriae type 1 · affects adults and children · can spread rapidlyEntamoeba histolyticaPicture: The colonic mucosa of a patient with amoebic dysentery.Image from The Wellcome Trust courtesy of Wenyon CM. Amoebic dysentery, caused by the protozoan Entamoeba histolytica: · affects mainly adults · is uncommon in children under 3 years of age · does not occur in large scale epidemics Pathophysiology of acute bloody diarrhoeaIn dysentery due to invasive bacteria (eg. Shigella, Campylobacter): 1. the bacteria infect the epithelial cells of the distal ileum and colon 2. bacteria multiply within the mucosal cells and spread between cells, killing them 3. extensive inflammatory damage is caused to the mucosa (see picture) S. dysenteriae type 1 also produces a toxin that causes haemolytic-uraemic syndrome (see screen 33). Image references ################ .\IMAGES\T33790.jpg .\IMAGES\T3612p.jpg Acute Bloody Diarrhoea - 2Clinical features Clinical features of shigellosis (bacillary dysentery) include: · frequent stools with blood and mucus (see picture)· fever and febrile convulsions · abdominal cramps · tenesmus · anorexia · dehydration - not usually severe · intestinal and extraintestinal complications How is a clinical diagnosis of shigellosis made?Picture: A stool from a patient with shigellosis. Copyright Image from Bennish M. Frequent stools Stools in a patient with shigellosis can be: · of small volume · passed 30 - 100 times per dayComplicationsThe most important complications of bacillary dysentery are: · haemolytic-uraemic syndrome in S. dysenteriae type 1 only (characterized by acute renal failure, haemolytic anaemia, thrombocytopenia) · hypoglycaemia · hyponatraemia · bacteraemia · rectal prolapse · toxic megacolon · intestinal perforation Clinical diagnosis of shigellosisPicture: A bloody mucoid stool from a patient with bacillary dysentery.Image from Behrens RH. It is important to diagnose shigellosis so that antibiotic treatment can be given. Bacillary dysentery is diagnosed clinically by: · loose or watery stools that contain visible red bloodor · a history of bloody stools reported by the child’s mother Image references ################ .\IMAGES\T45899.jpg .\IMAGES\T25584p.jpg Acute Bloody Diarrhoea - 3Treatment The key aspects of treatment of acute bloody diarrhoea are: · giving oral antibiotics for suspected shigellosis· giving oral antiparasitic drugs for diagnosed amoebic dysentery· prevention or treatment of dehydration, usually orally · continued breast feeding and early refeeding of solid food Map: The resistance of S. dysenteriae to antibiotics in selected African countries. The spread of multidrug resistant Shigella is rapid and ongoing. Ethiopia Burundi Zaire Zambia Resistance to: AmpicillinTMP-SMXNalidixic acid Copyright Image from The Wellcome Trust modified from Shears P. Ann Trop Med Parasitol 1996;90:105-14. Antibiotics for shigellosisPreferred antibiotics are: · ampicillin · trimethoprim-sulphamethoxazole · nalidixic acid · pivmecillinam · fluoroquinolones - licensed only for children over 15 yearsof age For details of doses refer to the tutorial Diarrhoeal Diseases: Acute Bloody Diarrhoea. Cheapest Most expensive Antiparasitic drugs for amoebic dysenteryPicture: Microscopic diagnosis of amoebic dysentery. This is a trophozoite of Entamoeba histolytica which has ingested red blood cells. Image from London School of Hygiene and Tropical Medicine. Indications for metronidazole treatment of amoebic dysentery are: · detection of Entamoeba histolytica trophozoites, containing red blood cells, in a fresh stool sampleor · clinical failure of two different antibiotics normally effective against Shigella Image references ################ .\IMAGES\Sdafr.gif .\IMAGES\T22836p.jpg Acute Bloody Diarrhoea: AssessmentA 3-year-old girl presents with a history of frequent bloody stools for 2 days, fever and abdominal cramps. She has signs of some dehydration. What is your clinical diagnosis? For the answer. What is your initial treatment? For the answer. If the drug treatment fails, what would you do next? For the answer.To return to the start of the section. Answer: Clinical diagnosisThe girl has acute bloody diarrhoea so the clinical diagnosis is shigellosis. The fever and abdominal cramps support this diagnosis.Answer: Initial treatmentInitial treatment includes: · ORT with early refeeding for the dehydration · an appropriate antibiotic against Shigella, eg. ampicillin, trimethoprim- sulphamethoxazole or nalidixic acidAnswer: If drug treatment failsTreatment failure could be because: · the strain of Shigella is resistant to the antibiotic used - a different drug should be given · the dysentery is not shigellosis - metronidazole for amoebic dysentery should be given if indicated by microscopy Image references ################ Persistent Diarrhoea including Severe MalnutritionPersistent Diarrhoea including Severe Malnutrition Image references ################ Persistent Diarrhoea including Severe Malnutrition - 1Aetiology of persistent diarrhoea Persistent diarrhoea is multifactorial in origin. It is associated with: · enteric infection · malnutrition · micronutrient deficiency · impaired immunity · a history of measles · lactose intolerance Picture: Diagnosis of enteroaggregative E.coli, which is associated with some cases of persistent diarrhoea. This form of E. coli has a characteristic aggregative pattern of adherence to a monolayer of cultured HEp-2 cells.Copyright Image from Knutton S. Multifactorial originMost of the factors listed probably favour persistent diarrhoea through: · increased susceptibility to enteric infections · delayed or ineffective repair of the damaged intestinal epitheliumEnteric infectionPersistent diarrhoea is associated with most of the same pathogens as acute diarrhoea, especially: · enteroaggregative E. coli (see picture) · Cryptosporidium - notably in HIV positive patients· Shigella · Giardia lamblia MalnutritionPictures: Bowel histology in normal small bowel (top) and persistent diarrhoea-malnutrition syndrome (bottom) in Gambian children.Images from Behrens RH. Persistent diarrhoea-malnutrition syndrome is characterized by the following histological changes to the small bowel: · a thin mucosa · blunt microvilli · subtotal villous atrophy and crypt hyperplasia Micronutrient deficiencyPicture: Severe vitamin A deficiency shown by xerophthalmia.Image from Sommer A. A Fieldguide to the Detection and Control of Xerophthalmia. Geneva: WHO, 1978. Persistent diarrhoea is particularly associated with deficiencies of: · vitamin A (see picture) · zinc Image references ################ .\IMAGES\T45926.jpg .\IMAGES\T45340bp.jpg .\IMAGES\T14050p.jpg Persistent Diarrhoea including Severe Malnutrition - 2Clinical features of persistent diarrhoea Clinical features of persistent diarrhoea include: · watery or bloody diarrhoea lasting at least 14 days · malnutrition (see picture)· micronutrient deficiency · associated non-intestinal infections· lactose intolerance in some cases · dehydration - not usually severe What is the role of laboratory investigations in persistent diarrhoea?Picture: A Bangladeshi child before (left) and after (right) persistent diarrhoea. Note the severe malnutrition.For more details.Copyright Images from Behrens RH. MalnutritionAssessment of nutritional status in a child with persistent diarrhoea is particularly important because: · persistent diarrhoea and malnutrition are closely linked · children with persistent diarrhoea and malnutrition need treatment in hospital Non-intestinal infectionsNon-intestinal infections are common causes of death in children with persistent diarrhoea and malnutrition. The most important infections are: · acute respiratory infection, eg. pneumonia · septicaemia · urinary tract infection · otitis mediaDehydrationDehydration in children with persistent diarrhoea: · is less common than in those with acute watery diarrhoea · carries a high risk of death when it does occur Remember that the degree of dehydration is difficult to assess in a child with severe malnutrition. Persistent diarrhoea and malnutritonPersistent diarrhoea is: · a major cause of malnutrition in developing countries · more common, and much more likely to be fatal, in children with pre-existing malnutritionThe role of laboratory investigationsPicture: Trophozoites of G. lamblia shown by light microscopy of a stool sample.Image from Centers for Disease Control and Prevention. Where available, techniques to support the clinical assessment include: · stool microscopy for parasites, eg. Giardia lamblia · stool culture for bacterial pathogens, eg. Shigella · immunological and nucleic acid based methods · tests of stool chemistry to help diagnose carbohydrate malabsorption Image references ################ .\IMAGES\T45345b.jpg .\IMAGES\T33307p.jpg Persistent Diarrhoea including Severe Malnutrition - 3Treatment of persistent diarrhoea The key aspects of treatment of persistent diarrhoea are: · appropriate dietary management · giving oral antibiotics for diagnosed: - enteric infections, eg. Shigella, Giardia - non-intestinal infections, eg. pneumonia· giving micronutrient supplementation · prevention or treatment of dehydration Children with persistent diarrhoea and severe malnutrition need specialist management (see screen 40). Picture: Making up food for giving to a child with persistent diarrhoea. Dietary management is central to the treatment of persistent diarrhoea. What are the objectives of feeding?Copyright Image from Behrens RH. Objectives of feedingManagement of a child with persistent diarrhoea aims to restore: · weight gain · normal intestinal function Because lactose intolerance is a factor in some children with persistent diarrhoea, lactose intake is progressively reduced by: · restricting the intake of animal or formula milk · replacing animal or formula milk with yogurt, which contains less lactose · feeding a diet that is completely free from lactose Breast feeding is not often associated with lactose intolerance and is encouraged.Summary of Diets for Children with Persistent Diarrhoea1Age At home In hospital Infants up to Breast milk Breast milk 4 - 6 months Yogurt Yogurt Animal orLactose free formula milk2 formula milkOlder childrenMilk as above Breast milk Cereals, vegetables, 1. Cereal-milk3- vegetable oil; sucrose-vegetable oil meat, fish, eggs 2. Cereal-egg/chicken- and fruit as available glucose-vegetable oil1. The diet should provide at least 110 kcal (0.46 MJ)/kg body weight daily. 2. Limited to less than 50 ml/kg body weight daily. 3. Lactose limited to less than 3.7 g/kg body weight daily (about 60 ml cow’s milk/kg).Less preferred options Less preferred options PneumoniaChildren with persistent diarrhoea and serious non-intestinal infection such as pneumonia should be treated in hospital. Other indications for hospital treatment are: · moderate or severe malnutrition · signs of dehydration DehydrationDehydration in children with persistent diarrhoea: · can be treated with oral fluids in the majority of patients · is rarely severe, but dehydration of any degree is a serious sign · should always be managed in hospital Image references ################ .\IMAGES\T45361.jpg Persistent Diarrhoea including Severe Malnutrition - 4 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 Treatment of diarrhoea with severe malnutrition Note. Children with diarrhoea and severe malnutrition should be treated as inpatients. The ten steps of treatment (see picture) cover two phases: 1. stabilization 2. rehabilitation Picture: Steps in the management of a child with severe malnutrition.With iron No iron Rehabilitation 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 · micronutrientsManagement of dehydrationRehydration of children with severe malnutrition is different from that of well nourished children. Oral rehydration is carried out: · with a modified ORS solution that reduces the risk of precipitating heart failure · cautiously to avoid overhydration Intravenous rehydration, restricted to children with severe malnutrition and hypovolaemic shock, should be given:· with extreme caution because of the risk of overhydration · using Ringer’s lactate with 5% dextrose, or half-normal saline with 5% dextrosePrevention/treatment of infectionSeverely malnourished children usually have one or more infections but fail to show signs, eg. fever. They should be given: · broad spectrum antibiotics for5- 7 days · measles vaccination if aged above 6 months · treatment for diagnosed infections, eg. shigellosis or tuberculosis Cautious feedingDuring stabilization the child should be fed cautiously with: · a milk based starter formula (‘F-75’) · oral or nasogastric feeding · 100 kcal/kg/day · 1 - 1.5 g protein/kg/day · continued breast feeding The aim is to provide just enough protein and energy to maintain basic physiological processes. Feeding for catch-up growthDuring catch-up growth the child should be fed: · a milk based catch-up formula (‘F-100’) · 150 - 220 kcal/kg/day · 4 - 6 g protein/kg/day · continued breast feeding Readiness to enter this phase is indicated by the return of the child’s appetite, usually after 1 week of treatment. 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 - a child with severe malnutrition has poor homeostasis · heart failureNoteTreatment of severe malnutrition is included with persistent diarrhoea in this tutorial for convenience, because severe malnutrition is often associated with persistent diarrhoea. However, severe malnutrition can also occur in a child with: · acute diarrhoea, particularly after recurrent episodes of acute diarrhoea · no history of diarrhoea Image references ################ .\IMAGES\Tenstep2.gif .\IMAGES\T45818p.jpg Persistent Diarrhoea including Severe Malnutrition: AssessmentA 9-month-old boy presents with a history of bloody stools for 16 days. He has moderate malnutrition and no signs of dehydration. Where should the boy be treated? For the answer. What dietary management do you recommend? For the answer. Are antibiotics indicated? For the answer.To return to the start of the section. Answer: Where the boy is treatedThe boy should be treated as an inpatient because he has moderate malnutrition. Other indications for hospital admission would be: · any degree of dehydration · any serious non-intestinal infectionAnswer: Dietary managementThe key aspects of dietary management are: · continued breast feeding · a first line diet of cereal, animal milk or yogurt, sucrose and vegetable oil to provide 110 kcal/kg/day · at least twice the recommended daily allowance of vitamins and mineralsAnswer: AntibioticsAntibiotics should be given for: · suspected shigellosis · diagnosed non-intestinal infections, eg. tuberculosis Broad spectrum antibiotics should not be given as the child does not have severe malnutrition. Image references ################ Defence MechanismsDefence Mechanisms Image references ################ Defence Mechanisms - 1Gastrointestinal (GI) defence What is the role of the GI tract indefence? Intestinal defence mechanisms can be classified as: · non-immunological protective factors (see picture)· immunological mechanisms: - innate immunity, eg. in inflammation - humoral immunity- cell-mediated immunity Where are the immunological responses generated?Saliva Mucus Peristalsis Gastric acid Proteolytic enzymes Bile Cryptdins Epithelial turnover Commensalbacteria Picture: Non-immunological factors in the GI tract. Copyright Image from The Wellcome Trust. Gastric acidThe acidic environment of the stomach (pH of 2 - 3): · degrades toxins · kills many bacterial pathogens, eg. V. cholerae O1 · does not kill the cysts of parasites, eg. Entamoeba histolytica Reduced secretion of gastric acid (hypochlorhydria) causes an increased risk of infection. It is commonly due to: · malnutrition · old age · infection · gastrectomy · treatment with H2 receptor antagonistsCommensal bacteriaThe healthy bowel contains a characteristic distribution of commensal bacteria, the ‘bowel flora’. These bacteria: · compete with enteric pathogens for nutrients and sites of adhesion · help to maintain normal bowel structure · secrete antimicrobial factors, eg. colicins and short chain fatty acidsRole of the GI tract in defenceTo maintain health the GI tract has to: · defend the body against ingested pathogens and their toxins · tolerate a massive antigenic load from: - commensal bacteria in the healthy bowel - ingested food Maintaining a balance between defence and tolerance requires tight regulation.Generation of immune responsesPicture: Structure of the villus in the small bowel showing the epithelium (E) and lamina propria (LP). Image from The Wellcome Trust. E The immunological responses are produced by an interaction between the: · mucosal immune system in the intestinal lamina propria and epithelium · systemic immune system in the circulating bloodLP Protective factorsA range of non-specific protective factors have evolved to maintain the integrity of the GI mucosa. They: · physically limit contact between the pathogen and host epithelium · chemically inactivate pathogens or their productsHumoral immunityHumoral (antibody dependent) immunity, especially secretory IgA, is the major mechanism of defence against pathogens in the bowel lumen. Humoral immunity: · developed later in evolution than innate immunity · is highly specific, due to binding between antibody and antigen · is adaptive - a stronger response develops after repeat exposure to the antigen, ie. immunological ‘memory’ Image references ################ .\IMAGES\Gitract4.gif .\IMAGES\Gvillus3.jpg Defence Mechanisms - 2Effector mechanisms4. Humoral immunity: secretory immunoglobulin A (sIgA) The main mucosal humoral response due to sIgA can be divided into four steps: 1. immunological induction 2. lymphocyte migration 3. antibody secretion 4. effector mechanisms Are there any other humoral immune responses in the bowel?Picture: The mucosal humoral immune response. Click on the numbers in the picture for details. Antibody secretion 3. Antigen 1. B and T cells B and T cells 2. Thoracic duct Lymph nodes Copyright Image from The Wellcome Trust. 3. Secretion of IgADuring the secretion of IgA in the bowel lumen: 1. plasma cells in the lamina propria produce dimeric IgA 2. IgA binds to a receptor on the basolateral surface of enterocytes 3. receptor-IgA is taken up and transported across the cell 4. secretory IgA is released into the bowel lumen1. InductionInduction of B and T lymphocytes in response to antigen happens at specific sites in the gut associated lymphoid tissue (GALT). These are: · Peyer’s patches, aggregations of lymphoid follicles in the small bowel · solitary lymphoid follicles in the large bowel 2. Lymphocyte migrationLymphocytes primed at Peyer’s patches and the solitary lymphoid follicles migrate around the body to the: 1. lymphatic system 2. mesenteric lymph nodes 3. thoracic duct 4. systemic circulation 5. intestinal lamina propria and other mucosal sites, eg. breast and lung The migration of primed lymphocytes to multiple mucosal sites means that there is a common mucosal immune system. sIgAPicture: The structure of sIgA. Image from The Wellcome Trust.Secretory component The structure of sIgA (see picture) is: · different from that of ‘standard’ serum antibodies such as IgG · a dimer of two IgA molecules joined by smaller protein chains · important for the function and stability of sIgA in the bowel lumen J chain 4. Effector mechanismssIgA in the bowel lumen prevents pathogens and toxins from invading the epithelium. The main mechanisms are: · agglutination of pathogens in the lumen · formation of immune complexes with luminal antigens · neutralization of toxins, viruses and bacteria sIgA does not activate complement and so the mucosal humoral response is not primarily inflammatory. Humoral Immune Responses in the Bowel Mucosal (bowel) Systemic (blood) immune systemimmune system sIgA sIgM IgGIgE2 1. IgG and IgE are important in inflammatory reactions to invasive pathogens such as Shigella and Salmonella. Some IgG also leaks into the bowel lumen. 2. IgE is also important in the response to intestinal helminths. Secreted into lumen Smaller amounts Active in lamina propria1Image references ################ .\IMAGES\Mucusumm.gif .\IMAGES\Siga2.gif Defence Mechanisms - 3For picture legend. Inflammation and the innate response Invasive pathogens (eg. Shigella) cause an acute inflammatory reaction. The immunological effector mechanisms include: · activation of complement · phagocytic and cytotoxic macrophages, polymorphonuclear neutrophils (PMNs) and natural killer (NK) cells · infiltration of inflammatory cells into the lamina propria · degranulation of mast cells and eosinophils For more details of regulation. How does this innate response interact with humoral immunity? Infected epithelial cell IL-8 Chemotaxis PMN or macro-phage Mast cell LTB4 MCP-1 Histamine IL-1 Infected macrophage Vascular permeability Extravasation Copyright Image from The Wellcome Trust. Picture legend Picture: Mediators of the inflammatory reaction. The picture shows examples of cells that produce inflammatory mediators (a macrophage, mast cell and intestinal epithelial cell) and examples of immune effector cells (a macrophage and PMN). The scheme is simplified and shows only selected interactions.Acute inflammatory reactionAt a gross physiological level the acute inflammatory reaction is defined by:· increased blood supply· increased permeability of capillaries and venules · extravasation of immune cells from venules into the lamina propria These inflammatory processes: · are triggered by the proinflammatory cytokines: interleukins 1 and 6, and tumour necrosis factor a · concentrate the products of the immune system at the site of infection · involve the mucosal and systemic immune systemsInflammatory cellsExtravasated inflammatory cells: · include PMNs and macrophages in the lamina propria · are attracted to the site of infection (chemotaxis) by soluble mediators · may cross the intestinal epithelium, enter the bowel lumen and be detectable by microscopy of a stool sampleDetails of regulation of acute inflammation Increased vascular permeability is due to vasoactive mediators such as: · interleukin 1 from activated macrophages · histamine from mast cells and eosinophils Chemotaxis of immune cells to the site of infection is regulated by molecules such as: · interleukin 8 from infected intestinal epithelial cells · monocyte chemoattractant protein 1 from infected intestinal epithelial cells · leukotriene B4 from mast cells · C5a from the complement cascade Interaction of innate and adaptive responsesMost invasive pathogens evoke both innate and adaptive immune responses. Innate responses interact with products of the adaptive immune system to become: · amplified · highly specific These products of the adaptive system include: · cytokines, eg. from T cells, macrophages and intestinal epithelial cells · antibodies, eg. serum derived IgG Image references ################ .\IMAGES\Airncks.gif Defence Mechanisms - 4Mucosal vaccines Mucosal vaccines: · aim to avoid the limitations of parenteral immunization · are introduced by a diverse range oforal delivery systems · induce mucosal (eg. sIgA) and systemic (eg. serum IgG) immune responses Picture: Cholera is one of several diarrhoeal diseases for which mucosal vaccines are been developed. Which other diarrhoeal diseases are being targeted?Copyright Image from Centers for Disease Control and Prevention. LimitationsParenteral immunization: · is expensive · requires attendance by a health worker · can cause adverse effects of injection, eg. abscess · carries a risk of transmitting HIV and hepatitisOral delivery systemsThe range of antigen delivery systems includes:· coadministration of antigen with immunogenic toxins, eg. cholera toxin B subunit · killed whole cells · live attenuated organisms · particulate carriers, eg. microspheres · recombinant ‘edible vaccines’, eg. transgenic plants Vaccines for diarrhoeal diseasesDiarrhoeal diseases for which vaccines are being developed include: · cholera· rotavirus · shigellosis · enterotoxigenic E. coli · salmonellosis Image references ################ .\IMAGES\T33079n.jpg Defence Mechanisms - 5The basis of protection from diarrhoea in breast fed infants. For a summary.Development of mucosal immunity Important aspects of the development of GI defence mechanisms are: · transfer of maternal IgG acrossthe placenta · transfer of maternal factors(eg. sIgA) in breast milk · development of the bowel flora Why does the incidence of diarrhoea peak in young infants? Antigen 1. 3. Other sites Passive immunity. Maternal bowel 4. Infant bowel Migration 2. Lymph nodes Thoracic duct Copyright Image from The Wellcome Trust modified from Brandtzaeg P. Development of the mucosal immune system in humans. In: Bindels JG, Goedhart AC, Visser HKA, eds. Recent developments in infant nutrition. London: Kluwer Academic, 1996:349-76.Breast milkBreast feeding protects against diarrhoea (see screen 14) because breast milk contains: · large quantities of sIgA, about 12 g/l in colostrum · lesser amounts of sIgM · immune cells, eg. macrophages, PMNs and T cells · non-specific protective factors, eg. lysozyme and lactoferrin · bifidus factor Passive immunityThese are examples of passive immunity because the fetus or baby receives functional antibodies or immune cells from the mother, instead of producing its own.Protection by breast feedingSteps in the transfer of immunity through breast feeding are: 1. induction of a humoral response in the mother’s bowel 2. migration of lymphocytes from GALT to the breast 3. secretion of sIgA and sIgM in the lactating mammary gland 4. ingestion of antibodies by the breast feeding infant The antibodies transferred are specific to antigens that the mother has previously encountered. Peak in young infantsThe peak incidence of diarrhoea in developing countries is in children aged 6 - 12 months. This peak reflects: · introduction of contaminated weaning foods and liquids · increased exposure to faeces in the environment · poorly developed defence mechanisms such as: - limited production of gastric acid - a leaky mucosa - immunological immaturity Image references ################ .\IMAGES\Entomamm.gif Defence Mechanisms: AssessmentAre the following statements about defence mechanisms against diarrhoea true or false? To return to the start of the section. Click on the True or False button for each statement. 1. Non-immunological protective factors in the GI tract act as a first line of defence against pathogens. 2. The major part of the mucosal humoral response is due to secretory IgM.3. Invasive pathogens evoke an inflammatory and IgG response in the lamina propria.4. Breast feeding transfers specific and non-specific factors to the infant.Correct These non-specific chemical and physical factors include: · saliva· mucus· gastric acid · peristalsis · normal bowel floraIncorrect Text 11 pt Arial dark blue goes here Incorrect These non-specific chemical and physical factors include: · saliva· mucus· gastric acid · peristalsis · normal bowel floraCorrect Text 11 pt Arial dark blue goes here Correct Text 11 pt Arial dark blue goes here Incorrect The dominant product of the mucosal humoral response is secretory IgA. sIgM is produced in significant but much smaller amounts.Incorrect Text 11 pt Arial dark blue goes here Correct The dominant product of the mucosal humoral response is secretory IgA. sIgM is produced in significant but much smaller amounts.Correct Invasive pathogens such as Shigella evoke: · an acute inflammatory response · mucosal (sIgA) and systemic (IgG) humoral responsesIncorrect Text explaining the answer (11-pt plain blue) Incorrect Invasive pathogens such as Shigella evoke: · an acute inflammatory response · mucosal (sIgA) and systemic (IgG) humoral responsesCorrect Text explaining the answer (11-pt plain blue) Correct Immunologically specific factors in breast milk include: · sIgA and sIgM · macrophages, PMNs and T cells Immunologically non-specific factors in breast milk include: · lysozyme and lactoferrin · bifidus factorIncorrect Text 11 pt Arial dark blue goes here Incorrect Immunologically specific factors in breast milk include: · sIgA and sIgM · macrophages, PMNs and T cells Immunologically non-specific factors in breast milk include: · lysozyme and lactoferrin · bifidus factorCorrect Text 11 pt Arial dark blue goes hereImage references ################ Summary Click on the buttons below for summary information. This child playing near a sewage outflow is at high risk of diarrhoeal disease.EpidemiologyPrevention and Control Principles of Case Management Acute Watery DiarrhoeaAcute Bloody Diarrhoea Persistent Diarrhoea includingSevere MalnutritionDefence Mechanisms Copyright Image from Cutting WAM. EpidemiologyDiarrhoea pathogens are spread by faecal-oral transmission through: · contamination of food · faecal contamination of drinking water · direct person to person spread Diarrhoea is associated with: · failure to breast feed · impaired immunity, eg. measles, HIV · malnutrition: the diarrhoea-malnutrition ‘vicious circle’ · poor weaning practice · poor food, domestic or personal hygiene · lack of clean water or sanitationPrevention and ControlMaternal and child health 1. Promotion of breast feeding. 2. Improvement of weaning practices. 3. Vitamin A supplementation. Immunization 4. Vaccination against rotavirus, cholera and measles. Interrupting transmission 5. Improvement of water supply and sanitation. 6. Promotion of personal and domestic hygiene. Case management 7. Improvement of the treatment of diarrhoea.Principles of Case ManagementIn a child with diarrhoea of any type, the key steps in treatment are: · prevention or treatment of dehydration: - extra fluids for no signs of dehydration - ORT for some dehydration - intravenous fluids for severe dehydration · appropriate nutritional management: - continuing breast feeding - refeeding solids after 4 - 6 hours of ORT · antimicrobials for specific enteric infections · treatment of associated infections or complicationsAcute Watery DiarrhoeaThe most important causes of acute watery diarrhoea are· rotavirus · enterotoxigenic E. coli· Vibrio cholerae O1 Clinical features include: · watery stools· vomiting · dehydration The key aspects of treatment are: · prevention or treatment of dehydration · continued breast feeding and early refeeding of solids · antibiotics for suspected choleraAcute Bloody DiarrhoeaThe most important causes of dysentery are Shigella and Campylobacter. Clinical features of shigellosis include: · frequent stools with blood and mucus · fever and febrile convulsions · anorexia · dehydration· intestinal and extraintestinal complications, eg. haemolytic-uraemic syndrome The key aspects of treatment are: · antimicrobials for suspected shigellosis or diagnosed amoebic dysentery · prevention or treatment of dehydration · continued breast feeding and early refeeding of solidsPersistent Diarrhoea-Severe MalnutritionPersistent diarrhoea is associated with enteric infection, malnutrition and impaired immunity. Clinical features include: · watery or bloody diarrhoea · malnutrition and micronutrient deficiency · non-intestinal infections · lactose intolerance in some cases · dehydration The key aspects of treatment are: · dietary management · oral antimicrobials for enteric and non-intestinal infections · prevention or treatment of dehydration Children with persistent diarrhoea and severe malnutrition need specialist management.Defence MechanismsA range of non-immunological protective factors in the GI tract includes: · gastric acid · commensal bacteria Immunological mechanisms include: · humoral responses to pathogens, eg. sIgA from the mucosal immune system, serum IgG from the systemic immune system · innate immune responses to invasive pathogens - an acute inflammatory reactionSection 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\T23720.jpg You have now finished the tutorial Overviewã The Trustee of the Wellcome Trust, 1998 Further reading Further activities Restart tutorial Picture: ORT in a young Bangladeshi woman.Copyright Image from Cutting WAM. Further reading Ashworth A. Nutrition interventions to reduce diarrhoea morbidity and mortality. Proc Nutrition Soc 1998;57:167-74. Bern C, Martines J, de Zoysa I, Glass RI. The magnitude of the global problem of diarrhoeal disease: a ten-year update. Bull World Health Organ 1992;70:705-14. Black RE. Persistent diarrhoea in children of developing countries. Pediatr Infect Dis J 1993;12:751-61. Booth IW, McNeish AS. Mechanisms of diarrhoea. Baillieres Clin Gastroenterol 1993;7:215-42. Brown KH. Dietary management of acute diarrheal disease: contemporary scientific issues. J Nutr 1994;124:1455-60S. Desjeux J-F, Briend A, Butzner JD. Oral rehydration solution in the year 2000: pathophysiology, efficacy and effectiveness. Baillieres Clin Gastroenterol 1997;11:509-27. Huttly SRA, Morris SS, Pisani V. Prevention of diarrhoea in young children in developing countries. Bull World Health Organ 1997;75:163-74. 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 management of bloody diarrhoea in young children. WHO/CDD/94.49. Geneva: WHO, 1994. Toy LS, Mayer L. Basic and clinical overview of the mucosal immune system. Semin Gastrointest Dis 1996;7:2-11.Further activities To look at pictures related to this tutorial, search the image collection using the following keywords: · epidemiology · prevention/control · treatment · clinical features - type of diarrhoea - acute watery diarrhoea · clinical features - type of diarrhoea - bloody diarrhoea · clinical features - type of diarrhoea - persistent diarrhoea · disease name - other diseases - severe malnutrition Image references ################ .\IMAGES\T44898.jpg