Acute Watery Diarrhoeaã The Trustee of the Wellcome Trust 1998Reviewed by: Professor B S Drašar, Department of Infectious and Tropical Diseases, London School of Hygiene andTropical Medicine and Dr W A M Cutting, Department of Child Life and Health, The University of Edinburgh, UK Picture: Oral rehydration being given for diarrhoeal dehydration in Bangladesh. Copyright Image from Cutting WAM.Image references ################ .\IMAGES\T44893.jpg Contents Click on the underlined text to jump tothat screen. Screen 3 Objectives 4Introduction 5Aetiology 12 Assessment 13 Epidemiology 21 Assessment 22 Pathophysiology 26 Assessment 27 Clinical Features andLaboratory Diagnosis 35Assessment 36 Management45 Assessment 46Summary Picture: A slum in Bangladesh. Living conditions here favour the transmission of diarrhoeal diseases such as cholera. Underlined text is interactive. Click on underlined text to view extra information or to jump to another screen. Copyright Copyright Image from Tomkins AM.Image references ################ .\IMAGES\T25669c.jpg ObjectivesAt the end of this tutorial you should be able to: 1. name the three main pathogens that cause acute watery diarrhoea: · rotavirus · enterotoxigenic Escherichia coli · Vibrio cholerae O1 2. describe the epidemiology of the key pathogens 3. summarize how the pathogens cause acute watery diarrhoea 4. describe the clinical features of acute watery diarrhoea and the role of laboratory diagnosis 5. review the management of a patient with acute watery diarrhoea 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 acute watery diarrhoea. Picture: A boy in hospital with acute watery diarrhoea. He is lying on a cholera cot, which contains a hole above a bucket on the floor to collect the stool. Note the bottle of oral rehydration solution by the bed.Copyright Image from Bryceson ADM. 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\T39733.jpg AetiologyAetiology Image references ################ Aetiology - 1Impact of acute watery diarrhoea Infectious diarrhoea presents as three clinical syndromes:· acute watery diarrhoea· dysentery or acute bloody diarrhoea· persistent diarrhoea In children under 5 years, acute watery diarrhoea (see pie charts) causes: · over 75% of all episodes of diarrhoea· 50% of all deaths from diarrhoea Pie charts: Annual numbers of episodes of diarrhoea and deaths from diarrhoea worldwide. Data from WHO 1995 and Bern et al 1992. Episodes Deaths200 million200 million1.4 billion1.2 million480,0001.6 millionAcute wateryAcute bloody Persistent Copyright Image from The Wellcome Trust based on data from the World Health Organization and Bern C, Martines J, de Zoysa I, Glass RI. Bull World Health Organ 1992;70:705-14.Acute watery diarrhoeaAcute watery diarrhoea: · is loose or watery stools without visible blood · lasts less than 14 days, often less than 5 - 7 days Acute bloody diarrhoeaAcute bloody diarrhoea or dysentery: · is loose or watery stools with visible blood · lasts less than 14 days, often less than 5 - 7 days Refer to the tutorial Diarrhoeal Diseases: Acute Bloody Diarrhoea. Persistent diarrhoeaPersistent diarrhoea: · is loose or watery stools with or without visible blood · lasts at least 14 days, sometimes 3 weeks or longer Refer to the tutorial Diarrhoeal Diseases: Persistent Diarrhoea. Deaths from diarrhoeaThe data shown probably underestimate the mortality due to persistent diarrhoea. Recent studies suggest that persistent diarrhoea may cause 45% of all diarrhoea deaths. Image references ################ .\IMAGES\Diapies.gif Aetiology - 2Aetiological agents of acute watery diarrhoea Two pathogens cause more than half of all the episodes of acute watery diarrhoea in children worldwide. These are: · rotavirus · enterotoxigenic Escherichia coli (ETEC) What is the next most important pathogen?Many other less common pathogens also cause acute watery diarrhoea (see table). Causes of Acute Watery Diarrhoea Viruses Rotavirus Small round structuredviruses, eg. Norwalk agent Enteric adenovirusesBacteria Enterotoxigenic E. coli V. cholerae O1 and O139 Shigella1 Campylobacter jejuni1 Non-typhoid Salmonella1 Enteropathogenic E. coliProtozoa Cryptosporidium1. These bacteria can also cause dysentery. Refer to the tutorial Diarrhoeal Diseases: Acute Bloody Diarrhoea. RotavirusPicture: Particles of rotavirus seen on electron microscopy.Image from Centers for Disease Control and Prevention. Rotavirus is the most important global cause of severe watery diarrhoea in children aged 6 - 24 months.ETECETEC is the: · most common bacterial cause of acute watery diarrhoea · pathogen most frequently implicated in traveller’s diarrhoeaNext most important pathogenA third pathogen, Vibrio cholerae O1, causes fewer deaths than either rotavirus or ETEC but is important because it can: · rapidly lead to very large fluid losses and severe dehydration · occur in large epidemics Image references ################ .\IMAGES\T33755p.jpg Aetiology - 3 Rotavirus Rotavirus is one of six genera of the family Reoviridae. The virus has a: · 70 nm spherical capsid · double stranded RNA of 11 segments Rotaviruses are classified into: · six groups (A - G)· 11 serotypes For other causes of viral diarrhoea.Picture: Particles of rotavirus from the stool of a patient with acute watery diarrhoea (EM). Note the intact particles (P) and ‘wheels’ from which the central core has been lost (W). W P Copyright Image from Booth IW. GroupsMost human rotaviruses are in group A. Other groups that infect humans include: · B - also infect rats and pigs · CSerotypesMost human infections are due to serotypes 1 - 4. Other viral diarrhoeasPicture: An adenovirus particle. Image from Emmerson AM. Other viruses with clinically similar effects to rotavirus include: · small round structured viruses, eg. Norwalk agent · enteric adenoviruses (see picture) Image references ################ .\IMAGES\T44889.jpg .\IMAGES\T31496p.jpg Aetiology - 4Enterotoxigenic E. coli E. coli is a Gram-negative bacillus. This species includes: · non-pathogenic bowel flora · pathogens causing diarrhoea: - enterotoxigenic E. coli (ETEC)*- enteropathogenic E. coli (EPEC)* - enteroinvasive E. coli (EIEC) - enterohaemorrhagic E. coli (EHEC) - enteroaggregative E. coli (EAggEC) *Causes of acute watery diarrhoea. Each of these five types of E. coli has: · associated O antigens · specific pathogenicity genes that determine virulencePicture: Enterotoxigenic E. coli (EM). Note the fimbriae.Copyright Image from Knutton S. O antigensO antigens are present in the polysaccharide part of the lipopolysaccharide in the cell wall of Gram-negative bacteria.Pathogenicity genesIdentification of the pathogenicity genes or their products is necessary to determine the E. coli type. Image references ################ .\IMAGES\T45904.jpg Aetiology - 5V. cholerae O1 V. cholerae O1 is a Gram-negative bacterium that is: · aerobic · ‘comma’ shaped (see picture) · motile The V. cholerae O1 serotype is divided into two biotypes: · classical· El Tor Picture: The characteristic comma shape of the cholera bacterium V. cholerae O1. This is a high power view under an oil emulsion lens.Copyright Image from The Wellcome Trust. MotileV. cholerae O1: · has a single polar flagellum· moves with characteristic darting movementsClassical biotypeThe classical biotype: · was the dominant biotype in the late 19th and early 20th century · spreads more slowly than the El Tor biotype · is now restricted to southern Bangladesh Image references ################ .\IMAGES\T1368.jpg Aetiology - 6V. cholerae O139 V. cholerae O139 was isolated in 1992. It is: · the first non-O1 serotype known to cause cholera · responsible for a cholera epidemic in the Indian subcontinent and parts of Southeast Asia (see map) · related to the El Tor biotype of V. cholerae O1 Map: The spread of V. cholerae O139. The V. cholerae O139 epidemic appears to have declined for the present. The epidemic is thus limited in geographical spread and duration. Data from Albert 1996.October 1992 March 1993 April 1995Copyright Image from The Wellcome Trust modified from Albert MJ. Indian J Med Res 1996;104:14-27. Non-O1 serotypesOther non-O1 serotypes of V. cholerae cause diarrhoea of lesser severity than V. cholerae O1 or O139. Related to V. cholerae O1 V. cholerae O139 is: · similar to V. cholerae O1 in its clinical effects · different from V. cholerae O1 in its epidemiology Image references ################ .\IMAGES\Vcbengal.gif Aetiology: AssessmentAre the following statements about the aetiology of acute watery diarrhoea true or false?To return to the start of the section. Click on the True or False button for each statement. 1. The most important causes of childhood acute watery diarrhoea are all bacteria.2. The peak incidence of rotaviral diarrhoea is in children aged under 2 years.3. The major type of E. coli that causes acute watery diarrhoea is enteroinvasive E. coli. 4. Most cases of cholera are caused by V. cholerae O139.Correct Text explaining the answer (11-pt plain blue) Incorrect The three most important causes of acute watery diarrhoea in children worldwide are: · rotavirus - a virus · enterotoxigenic E. coli - a bacterium · V. cholerae O1 - a bacteriumIncorrect Text explaining the answer (11-pt plain blue) Correct The three most important causes of acute watery diarrhoea in children worldwide are: · rotavirus - a virus · enterotoxigenic E. coli - a bacterium · V. cholerae O1 - a bacteriumCorrect Rotavirus is the most important cause of severe watery diarrhoea in children aged 6 - 24 months.Incorrect Text explaining the answer (11-pt plain blue) Incorrect Rotavirus is the most important cause of severe watery diarrhoea in children aged 6 - 24 months.Correct Text explaining the answer (11-pt plain blue) Correct Incorrect The most important type of E. coli to cause acute watery diarrhoea is enterotoxigenic E. coli. (Enteroinvasive E. coli causes bloody diarrhoea.)Incorrect The most important type of E. coli to cause acute watery diarrhoea is enterotoxigenic E. coli. (Enteroinvasive E. coli causes bloody diarrhoea.)Correct The most important type of E. coli to cause acute watery diarrhoea is enterotoxigenic E. coli. (Enteroinvasive E. coli causes bloody diarrhoea.)Correct Incorrect V. cholerae O139 is only a relatively minor global cause of cholera. V. cholerae O1 causes most cases of cholera worldwide.Incorrect V. cholerae O139 is only a relatively minor global cause of cholera. V. cholerae O1 causes most cases of cholera worldwide.Correct V. cholerae O139 is only a relatively minor global cause of cholera. V. cholerae O1 causes most cases of cholera worldwide. Image references ################ Epidemiology EpidemiologyImage references ################ Epidemiology - 1Rotavirus Diarrhoea due to rotavirus: · is important in developed and developing countries· occurs as a ‘winter epidemic’ in temperate countries (see graph)· affects mainly children aged under2 years Graph: Annual variation in the number of cases of rotavirus in England and Wales. The data shown are the average incidence of rotavirus cases between 1992 and 1995. Data from PHLS, Communicable Disease Surveillance Centre. No. of cases3000 2000 1000 0 12345678910 11 1213 4 week period (January to December) Copyright Image from The Wellcome Trust based on data from Public Health Laboratory Service, Communicable Disease Surveillance Centre.Rotavirus seasonalityRotaviral diarrhoea in tropical countries: · shows much less seasonality · is endemic throughout the yearChildren under 2 yearsRotaviral infection of older children and adults: · does occur · is clinically much less severe, partly because of immunity acquired from earlier infections Image references ################ .\IMAGES\Rotaepi.gif Epidemiology - 2Enterotoxigenic E. coli Diarrhoea 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 · affects 5 - 10 million visitors to developing countries annually (see map)15% 4% 41% 21% 42% 30% 45% 26% 14% 40% 33% 15% 25% 28% 26% 34% Map: The risk of traveller’s diarrhoea in Swiss travellers over a 2 week visit. Three levels of risk are seen: low (4 - 8%, eg. North America); moderate (8 - 20%, eg. the Caribbean, Southern Europe); and high (20 - 55%, eg. developing countries). Data from Castelli and Carosi 1995. Copyright Image from The Wellcome Trust modified from Castelli F, Carosi G. Chemotherapy 1995;41(Suppl 1):20-32.Traveller’s diarrhoeaNote that traveller’s diarrhoea is: · caused by a range of pathogens, eg. ETEC,C. jejuni, Shigella, Salmonella, rotavirus · not restricted to acute watery diarrhoea - it can be bloody or persistent · generally not of life threatening severity Image references ################ .\IMAGES\Wrldmap3.gif Epidemiology - 3Countries reporting cholera to the World Health Organization (WHO) in 1996 ( ). Data from WHO 1997. Endemic cholera Diarrhoea due to endemic V. cholerae O1: · is important in many developing countries (see map) · peaks in the warm season · affects mainly children aged 2 - 5 years Copyright Image from The Wellcome Trust modified from World Health Organization. Weekly Epidemiol Record 1997;72:229-36.Warm seasonThe weather affects the population of the following species in estuaries, all of which are probable reservoirs of V. cholerae O1: · cyanobacteria - cholera epidemics are linked to algal blooms · plankton · algae · crustaceans · oysters · fish Image references ################ .\IMAGES\Endchol.gif Epidemiology - 4Epidemic cholera During a cholera epidemic: · children and adults are affected · population movements spread disease The seventh V. cholerae O1 pandemic (see map) is unusual because it: · was caused by the El Tor biotype· started in Sulawesi, Indonesia rather than the Indian subcontinent · spread cholera to South America for the first time since 1896 The spread of the seventh cholera pandemic.Data from Shears and Hart 1996.1960s 1970s 1980s 1990s Copyright Image from The Wellcome Trust modified from Shears P, Hart CA. Gastrointestinal bacteria. In: Cook GC, ed. Manson’s tropical diseases. 20th ed. London: WB Saunders, 1996:824-48.Cholera Pandemics in Modern Times Countries affected Indian Southeast Pandemic subcontinentAsiaMiddle EastEuropeAfricaAmerica First (1817-1823) +++ -+ - Second (1826-1837) +++ ++ + Third (1842-1862) +++ ++ + Fourth (1865-1875) +++ ++ + Fifth (1881-1896) +++ ++ + Sixth (1899-1923) +++ ++ - Seventh (1961- ) + ++ ++ + Children and adults affectedPicture: A young woman with cholera. Image from Cutting WAM. In the recent epidemic of V. cholerae O139 (see screen 11): · 70% of cases were in people aged over 15 years · immunity to endemic V. cholerae O1 offered no protection against V. cholerae O139 El Tor biotypeThe fifth and sixth pandemics were due to the classical biotype.Population movementsMovement of people may be due to: · pilgrimage · immigration · trade · warImage references ################ .\IMAGES\Wrldchlr.gif .\IMAGES\T44898a.jpg Epidemiology - 5Faecal-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 spreadWhich factors favour transmission of diarrhoea?Picture: Modes of faecal-oral transmission. Food Drinking water Person to person Faecal contaminationof hands and clothes Contaminated with faeces Endogenous pathogens Contact, fingers putin mouth Not cooked thoroughly Copyright Image from The Wellcome Trust.Transmission factorsTransmission of diarrhoea is favoured by: · crowded living conditions · unsafe or insufficient water supply · inadequate sanitation · poor personal hygiene, eg. not washing hands · poor food hygiene · failure to breast feed exclusively until age 4 - 6 months Refer to the tutorial Diarrhoeal Diseases: Epidemiology.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 Contamination 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 Person to person spreadPerson to person contact involves faecal contamination of: · hands · clothes · fomites, eg. a towel Image references ################ .\IMAGES\Foraltsm.gif Epidemiology - 6Transmission of rotavirus Transmission of rotavirus: · is primarily by direct person to person spread· also occurs through contaminated water (see picture) · probably also happens by an airborne route The infective dose is low, 102 - 104 virus particles. This favours person to person transmission.Picture: The water which these women are collecting for use in the home may be faecally contaminated and so transmit rotavirus.Copyright Copyright holder unknown. Image from Hartley J. In: Diarrhoea, a major public health problem. Save the Children Fund. Person to person spreadExamples of direct person to person spread are: · from carer to child in daycare centres, which are common sites of outbreaks in developed countries · transmission within the family, eg. from mother to child Airborne routeThe evidence for airborne transmission of rotavirus is that: · infections in developed countries are not linked to poor sanitation · the epidemiology (eg. winter peak in temperate countries) shows similarities with that of diseases caused by respiratory viruses · upper respiratory tract symptoms are often associated with rotaviral diarrhoea Image references ################ .\IMAGES\T23778.jpg Epidemiology - 7Transmission of ETEC and V. cholerae O1 Transmission of these bacteria is primarily through faecally contaminated: · water · food (see picture) Does person to person spread occur? Infective doses are relatively high:· 106 - 1010bacteria for ETEC · 108 - 109bacteria for V. cholerae O1 Picture: Seafood, a common source of cholera, on sale at a market in a slum area of Jakarta, Indonesia. Many seafood organisms concentrate pathogens by filtering large amounts of water.Copyright Image from Bryceson ADM. Person to person spread Transmission by person to person spread: · is documented for ETEC · may possibly occur with V. cholerae O1Faecally contaminated foodContamination of food with V. cholerae O1 includes: · seafood and shellfish contaminated from the environment · food contaminated in storage or preparation · ‘freshening’ of vegetables with contaminated water Infective dosesThe infective dose is estimated by giving a known number of pathogens to a volunteer, who is usually: · an adult · well nourished · from a non-endemic area The infective doses cannot reliably be extrapolated to children: · from an endemic area · in a highly contaminated environment · with malnutrition and impaired immunity Image references ################ .\IMAGES\T39751.jpg Epidemiology: AssessmentThe table summarizes the epidemiology of acute watery diarrhoea caused by some of the common pathogens. Think about what text should be in each gap, then click on the gaps to reveal the answers. Pathogen Ages most affected Major modes of transmission RotavirusPerson to person, contaminatedwater, probably airborne ETEC Children and adults Endemic 2 - 5 yearscholera Epidemic cholera To return to the start of the section. 6 - 24 months Contaminated foodand water Children and adultsImage references ################ Pathophysiology PathophysiologyImage references ################ Pathophysiology - 1The three basic mechanisms of diarrhoea Diarrhoea reflects: · increased secretion by the intestineand/or · decreased absorption by the intestine Mechanisms of acute diarrhoea can be divided into three basic types (see picture): · secretory diarrhoea· invasive diarrhoea· osmotic diarrhoea Acute watery diarrhoea is generally of a secretory or non-inflammatory invasive aetiology.Picture: The basic mechanisms of diarrhoea.Secretory diarrhoea Na+ Cl- Toxin H2O Blood Invasive diarrhoea Exudate Pus Cell death Na+ Cl- InflammatoryNon-inflammatory H2O Na+ Cl- H2O Osmotic diarrhoea Osmoticpull H2O Copyright Image from The Wellcome Trust. Secretory diarrhoeaIn secretory diarrhoea: · excess secretion of fluid and electrolytes is caused by an enterotoxin · the pathogen does not invade enterocytes This type of diarrhoea (eg. cholera, ETEC) is watery. Invasive diarrhoeaIn invasive diarrhoea, reduced absorption is caused by the pathogen invading and damaging enterocytes and colonocytes. Invasive diarrhoea can be: · inflammatory (eg. Shigella) - causing bloody diarrhoea · non-inflammatory (eg. rotavirus) - causing watery diarrhoeaOsmotic diarrhoeaIn osmotic diarrhoea, reduced absorption is caused by an osmotically active non-absorbed substance (eg. lactose) in the bowel lumen. This type of diarrhoea is watery. Image references ################ .\IMAGES\Diarmech.gif Pathophysiology - 2Mechanism of non-inflammatory invasive diarrhoea due to rotavirus. Pathophysiology of rotaviral diarrhoea In rotaviral diarrhoea: 1. virus invades mature enterocytes in the proximal small bowel 2. viral multiplication damages enterocytes, causing increased enterocyte shedding and proliferation ( ) 3. reduced absorption is due to the: - low absorptive capacity of repopulatingcrypt like enterocytes*- smaller surface area of stunted villi* - fall in disaccharidase activity of damaged microvilli *Non-inflammatory invasive diarrhoea Shed enterocytes 1. 2. 3. Crypt hyperplasia Rotavirus Villous atrophy Villus Crypt Picture: The mechanism of rotaviral diarrhoea.Copyright Image from The Wellcome Trust. Crypt like enterocytesIn healthy bowel epithelium, enterocytes: · arise continuously from stem cells in the crypt region· migrate toward the villus apex · differentiate as they migrate from crypt to apex · are shed from the apex into the bowel lumen In epithelium infected with rotavirus, the increased rate of enterocyte shedding and proliferation means that the cells at the tips of villi are still of an immature secretory type.Disaccharidase activityThe fall in activity of disaccharidases (eg. lactase) causes an osmotic diarrhoea. For details refer to the tutorial Diarrhoeal Diseases: Organisms and Pathophysiology. Image references ################ .\IMAGES\Invadiar.gif Pathophysiology - 3Pathophysiology of ETEC and V. cholerae O1 diarrhoea These bacteria cause a secretory diarrhoea in which: 1. a soluble bacterial enterotoxin is taken up by the enterocyte 2. a G protein is modified and locked in the active state3. adenylate cyclase is activated, causing intracellular cAMP levels to rise 2. Gs-a Adenylate cyclase cAMP Gs 3. 1. Toxin Protein kinases 4. Cl- channels are opened and Na+-Cl- cotransporters are inhibited5. massive secretion of electrolytes and water follows Cl- 4. 5. Na+ Cl- Picture: The mechanism of diarrhoea due to cholera toxin.Copyright Image from The Wellcome Trust modified from Booth IW, McNeish AS. Baillieres Clin Gastroenterol 1993;7:215-42. EnterotoxinThe major enterotoxins produced are: · cholera toxin (CT) by V. cholerae O1 · heat labile toxin (LT) by ETEC Refer to the tutorial Diarrhoeal Diseases: Organisms and Pathophysiology.Modification of the G proteinIntracellular enterotoxin catalyses irreversible modification (ADP-ribosylation) of the a subunit of the G protein. This causes the G protein to: 1. be locked in its GTP-binding state 2. activate adenylate cyclase in the absence of appropriate stimuli Image references ################ .\IMAGES\Secrdiar.gif To return to the start of the section. How do bacterial secretory diarrhoea and rotaviral diarrhoea differ? Click your mouse on a box below.Hold the mouse down and drag the box to the correct column. Rotaviral diarrhoea Secretory bacterial diarrhoea Pathophysiology: Assessment Pathogen invades enterocytes Toxin taken up by enterocytes Secretion due to raised cAMP Secretion due to crypt like enterocytes at villus tip Villi appear stunted Villi appear histologically normal 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 now finished this assessment.Image references ################ Clinical Features and Laboratory Diagnosis Clinical Features and Laboratory DiagnosisImage references ################ Clinical Features and Laboratory Diagnosis - 1Effects of acute watery diarrhoea The clinical effects of acute watery diarrhoea reflect loss of: · water in stools, leading to dehydration · electrolytes in stools, leading to depletion of: - Na+ and Cl-- K+- HCO3- · water and electrolytes in vomit · water due to febrile sweating Why is the impact of diarrhoea greatest in youngchildren? Video: Acute watery diarrhoea in an Indian child. The large stool output means that the risk of dehydration developing is high. To run the video.Copyright Image and video from United Nations Children's Fund, India. K+ Loss of K+ (potassium) causes muscle cramping.HCO3-Loss of HCO3- (bicarbonate - a base) causes metabolic acidosis with deep breathing.Young children Children are more susceptible to dehydration than adults because their: · fluid and electrolyte exchanges are proportionately greater · renal function is less well developed· surface area (and hence losses through the skin) is relatively high · immunity to infection is less developed These differences do not mean that children are the only group at risk from diarrhoea. For example, epidemic cholera kills many adults. Image references ################ .\IMAGES\Diarrh1.jpg Clinical Features and Laboratory Diagnosis - 2Clinical features of rotaviral diarrhoea Rotavirus can cause: · watery or loose, pale stools with a milky smell· vomiting* · low grade fever* · mild abdominal cramps *These signs usually precede diarrhoea by several hours. How long do symptoms last? Picture: An Egyptian child with severe dehydration due to acute watery diarrhoea.Copyright Copyright holder unknown. Image supplied by Cutting WAM. Duration of symptomsRotaviral diarrhoea typically: · has an incubation period of 1 - 3 days · lasts 3 - 9 days, when it is not fatal StoolsDiarrhoea is more severe if the child: · is malnourished · has had measles in the past 6 weeks Image references ################ .\IMAGES\T22303.jpg Clinical Features and Laboratory Diagnosis - 3Clinical features of ETEC diarrhoea ETEC can cause: · watery or loose stools (see picture) · nausea · vomiting · abdominal cramps · fever in some cases How long do symptoms last? Picture: A watery stool from a patient with ETEC infection.Copyright Image from Tubbs HR. Duration of symptomsDiarrhoea due to ETEC typically: · has an incubation period of 1 - 2 days · lasts 1 - 5 days, when it is not fatal Image references ################ .\IMAGES\T22792.jpg Clinical Features and Laboratory Diagnosis - 4Clinical features of cholera V. cholerae O1 and O139 can cause: · painless frequent ‘rice water’ stools (see picture) of very high volume· effortless vomiting · abdominal cramps · fever in some cases · hypoglycaemia How long do symptoms last? Fluid losses through diarrhoea and vomiting can lead to circulatory collapse and death within hours. Picture: A stool from a patient with cholera. The characteristic ‘rice water’ stool contains flecks of mucus, is pale grey in colour and smells fishy. Copyright Image from Behrens RH. Duration of symptomsCholera typically: · has an incubation period of 2 - 3 days · if untreated lasts 1 - 5 days, when it is not fatalStool volumeStool volume can be: · more than 20 litres/day in adults · 8 - 10 ml/kg/hour in small childrenHypoglycaemiaHypoglycaemia can cause: · convulsions · coma Image references ################ .\IMAGES\T45352.jpg Clinical Features and Laboratory Diagnosis - 5Clinical features of traveller’s diarrhoea Traveller’s diarrhoea is: · diarrhoea which occurs during or shortly after travel · most common in people from developed areas visiting developing countries · acute watery diarrhoea in over 70% of cases · most commonly caused by ETEC, C. jejuni, Shigella and Salmonella (see pie chart)Causes of traveller’s diarrhoea.Data from Hart 1996.Giardia Entamoeba histolytica No pathogen isolated Rotavirus Campylo- bacter ETEC Salmonella Shigella Copyright Image from The Wellcome Trust modified from Hart CA. Introduction to acute infective diarrhoea. In: Cook GC, ed. Manson's tropical diseases. 20th ed. London: WB Saunders, 1996:817-23. Acute watery diarrhoeaAcute watery traveller’s diarrhoea is usually mild and rarely causes: · more than 6 stools per day · severe dehydration Traveller’s diarrhoea presents as: · acute bloody diarrhoea in about 20% of cases · persistent diarrhoea in 1 - 3% of cases Image references ################ .\IMAGES\Tdagents.gif Clinical Features and Laboratory Diagnosis - 6Viral versus Bacterial Diarrhoea Differential diagnoses of acute watery diarrhoea It is not generally possible to identify the pathogen causing acute watery diarrhoea from clinical features. It may be possible to make a provisional diagnosis (see table) between:· viral diarrhoea · bacterial diarrhoea This still leaves a wide range of potential pathogens of each type. Viral diarrhoea Bacterial diarrhoea Peak age of infection 6 - 24 months About 2 - 5 years in endemic areas Vomiting and feverPrecede diarrhoea Often do not precede diarrhoea Peak prevalence Cooler months Warmer months (seasonality) (temperate areas) Common pathogens Rotavirus, small ETEC,round structuredV. cholerae O1*, viruses Shigella, (eg. Norwalk agent) C. jejuni, Salmonella, EPEC*Diagnosis of severe cholera on clinical grounds is usually possible, especially if there is an epidemic in the area.Identification of the pathogenDefinitive identification of the pathogen requires a laboratory diagnosis.Image references ################ Clinical Features and Laboratory Diagnosis - 7 Laboratory Techniques to Identify Specific PathogensLaboratory diagnosis Laboratory identification of the pathogen causing acute watery diarrhoea is: · not necessary for treatment (and may take too long anyway) · required for epidemiological surveillance and determination of antibiotic sensitivity · often dependent on highly sophisticated techniques and equipment Pathogen Technique Rotavirus Antibody based methods to detectvirus particles Electrophoresis of viral RNA onpolyacrylamide gel Electron microscopy and immuneelectron microscopy ETECCulture from a stool sample or rectalswab Detection of pathogenicity genes byhybridization Detection of pathogenic gene productsby antibody methods V. cholerae O1Culture from a stool sample or rectalswab Dark field microscopy to see commas orrods with characteristic motilityAntibody based methodsPicture: A commercial enzyme immunoassay showing a positive result for rotavirus.Image from Bufton A, ABBOTT Laboratories Ltd.In the assay shown: 1. a faecal sample is placed in the well 2. rotaviral antigen binds to specific antibody 3. a chemical reaction causes the grey cross to appear CulturePicture: A culture of V. cholerae. Image from Ridgway GL.The culture plate shows colonies of V. cholerae growing on thiosulphate-citrate-bile salts-sucrose (TCBS) agar. Vibrios appear as medium sized, smooth, opaque, thin edged, yellow colonies. Image references ################ .\IMAGES\T45388p.jpg .\IMAGES\T33962p.jpg Clinical Features and Laboratory Diagnosis: AssessmentAre the following statements about acute watery diarrhoea true or false? To return to the start of the section. Click on the True or False button for each statement. 1. The most important acute clinical effects of watery diarrhoea are due to loss of water and electrolytes.2. Cholera can always be distinguished from diarrhoea due to rotavirus and ETEC by its clinical features.3. Acute watery diarrhoea of viral origin is more common in very young children than acute watery diarrhoea due to bacteria.4. Laboratory identification of the pathogen is necessary before treatment for diarrhoea can be given.Correct Water and electrolytes are lost in: · stools · vomit · sweat (fever)Incorrect Text 11 pt Arial dark blue goes here Incorrect Water and electrolytes are lost in: · stools · vomit · sweat (fever)Correct Text 11 pt Arial dark blue goes here Correct Text 11 pt Arial dark blue goes here Incorrect Severe cholera is usually possible to diagnose clinically but less severe cholera is not. (This also depends on whether there is an epidemic of cholera in the area.)Incorrect Text 11 pt Arial dark blue goes here Correct Severe cholera is usually possible to diagnose clinically but less severe cholera is not. (This also depends on whether there is an epidemic of cholera in the area.)Correct However, the age ranges of viral and bacterial diarrhoea overlap and so this information is not very helpful in making a diagnosis.Incorrect Text explaining the answer (11-pt plain blue) Incorrect However, the age ranges of viral and bacterial diarrhoea overlap and so this information is not very helpful in making a diagnosis.Correct Text explaining the answer (11-pt plain blue) Correct Incorrect Identification of the enteric pathogen is in general not necessary for treatment.Incorrect Text explaining the answer (11-pt plain blue) Correct Identification of the enteric pathogen is in general not necessary for treatment. Image references ################ ManagementManagement Image references ################ Management - 1Assessing a child with diarrhoea Clinical examination (see picture) and a brief history should follow these steps. 1. Assess the degree of dehydration. 2. Establish whether diarrhoea is watery or bloody. 3. Ask about the duration of diarrhoea. 4. Look for severe malnutrition and evaluate feeding practices. 5. Determine any concurrent illness and immunization history. Picture: A Nigerian child with diarrhoea being assessed. The child is also malnourished.Copyright Image from WHO Photo Library courtesy of Lejneu A. Immunization historyEvery opportunity to check immunization status should be taken. In particular, measles is: · preventable by vaccination · often accompanied by diarrhoea · a risk factor for subsequent severe and persistent diarrhoea · a major cause of death and disability in its own right Duration This is to distinguish between: · acute diarrhoea - duration less than 14 days (usually less than 5 - 7 days) · persistent diarrhoea - duration at least 14 daysImage references ################ .\IMAGES\T34919.jpg Management - 2 Assessment of dehydration Clinical assessment should establish the degree of water and electrolyte loss as one of: · no signs of dehydration · some dehydration · severe dehydration Treatment is different in each case.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. 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 (eg. fever, bloody stool) appear. Some dehydrationThese children need oral rehydration therapy (ORT) with oral rehydration salts (ORS) solution (see screen 41).Severe dehydration The degree of dehydration is assessed by physical examination using a standardized WHO chart. Examination is made of the patient’s: · skin turgor (see video) · general condition and behaviour · eyes · tears · mouth and tongue · thirst Refer to the tutorial Diarrhoeal Diseases: Clinical Assessment.Severe dehydrationThese children need urgent intravenous rehydration (see screen 42). Refer to the tutorial Diarrhoeal Diseases: Rehydration and Early Feeding. Image references ################ .\IMAGES\Diarrh4.jpg Management - 3Clinical diagnosis of cholera Cholera is diagnosed clinically when: · a child aged over 5 years or an adult (see picture) with acute watery diarrhoea develops severe dehydration · anyone aged over 2 years develops acute watery diarrhoea during a cholera outbreak Why is a diagnosis of choleraimportant? Picture: An adult with severe dehydration due to cholera. Note the sunken eyes.Copyright Image from Bryceson ADM. Clinical diagnosis of choleraA presumptive clinical diagnosis of cholera is important because it is the most rapidly dehydrating diarrhoea and requires: · early and effective rehydration· antibiotic treatment An effective antibiotic given promptly reduces the: · duration of diarrhoea · severity of diarrhoea · risk of severe dehydrationAged over 5 years Endemic cholera does affect younger children. However, acute watery diarrhoea in this age group is more often due to other causes (eg. rotavirus) and so a clinical diagnosis of cholera cannot be reliably made. Image references ################ .\IMAGES\T39750.jpg Management - 4Treatment of a child with acute watery diarrhoea In a child with acute watery diarrhoea, the key steps in treatment are: · prevent dehydration if there are no signs of dehydration · treat dehydration when it is present· breast feed throughout the diarrhoea episode · restart solid food after initial oral rehydration · give antibiotics if cholera is suspected· do not give antidiarrhoeal drugs, eg. loperamide For related tutorials. Picture: ORT being given to a 9-month-old Bangladeshi girl with acute watery diarrhoea. Copyright Image from Cutting WAM. Related tutorials Refer to the Diarrhoeal Diseases tutorials: · Rehydration and Early Feeding · The Role of Diet and Drugs RehydrationThe aim of rehydration is to replace lost: · water· electrolytes Image references ################ .\IMAGES\T44894.jpg Management - 5Oral rehydration therapy (ORT) Patients with some dehydration need ORT. Health workers should be able to: · prepare ORS solution from a sachet· estimate how much ORS solution to give in the first 4 hours · show the mother how to give ORT · monitor the child’s rehydration · instruct about continuing treatment at home · identify patients who cannot be treated by ORT Picture: A mother giving her 4-month-old child ORT. Infants should be given frequent small volumes of ORS solution by cup and spoon. What is the basis for ORT? Copyright Image from Cutting WAM. Frequent small amountsFluids should be given: · with a teaspoon every 1 - 2 minutes to children under 2 years (feeding bottles should not be used) · as frequent sips from a cup for older children and adults ORT requires patience and perseverance on the part of the carer.ORS solutionORS solution: · is a solution of salts and glucose of a defined composition · contains electrolytes in concentrations similar to those in a watery stool Refer to the tutorial Diarrhoeal Diseases: Rehydration and Early Feeding.Patients who cannot take ORTPicture: A Jamaican child with diarrhoea being rehydrated by nasogastric tube. . Image from Golden M.Rehydration in children who cannot take ORT is by: · nasogastric tube · intravenous infusion Refer to the tutorial Diarrhoeal Diseases: Rehydration and Early Feeding. Treatment at homeORT should ideally be: · started under supervision in a health clinic · finished at home under the mother’s care 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 · Na+, K+ and Cl- replace losses of these electrolytes in the stool · citrate helps correct acidosis However, rehydration with standard ORS solution does not reduce the: · stool output· duration of diarrhoea Image references ################ .\IMAGES\T44892.jpg .\IMAGES\T27811p.jpg Management - 6Intravenous rehydration Clinical assessment should identify children with: · severe dehydration· shock or circulatory collapse These children are at immediate risk of death and need urgent intravenous rehydration. Intravenous rehydration should also be considered in a child: · who has not improved after 2 - 4 hours of adequate ORT· in whom ORT greatly increases stool volume · with abdominal distension Picture: Setting up an infusion into the scalp vein of an infant with severe dehydration. Very rapid infusion may be necessary in a patient with cholera. For more details. Copyright Image from Cutting WAM. Scalp veinPreferred veins are in the: · back of the hand · forearm · side of the scalp in infants (see picture) · front of the elbow in older children and adults Adults with severe circulatory collapse may initially need two intravenous lines at once. Shock or circulatory collapseSigns of shock or circulatory collapse are: · rapid weak (or absent) radial pulse · unrecordable blood pressure· reduced consciousness or lethargy · cool and moist hands or feet · slow capillary refilling of nailbeds (more than 2 seconds) Intravenous rehydrationIntravenous rehydration should be performed by trained staff 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. Image references ################ .\IMAGES\T23740a.jpg Management - 7Nutrition in acute watery diarrhoea Diarrhoea is a major contributor to poor nutritional status. To prevent the development of malnutrition and promote repair of the bowel, good feeding practice is needed during the diarrhoea episode. 1. Breast feeding should be continued throughout (see picture). 2. Older children should be given solid food after 4 - 6 hours of oral rehydration. 3. An extra daily meal should be given for at least 2 weeks after treatment. Picture: Breast feeding in an oral rehydration clinic.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. Diarrhoea and malnutritionDiarrhoea causes nutritional decline through: · reduced dietary intake · increased metabolic rate · direct losses · reduced digestion and absorption of nutrients Refer to the tutorial Diarrhoeal Diseases: The Role of Diet and Drugs. Breast feedingBreast feeding throughout an episode of diarrhoea reduces the: · severity of diarrhoea · duration of diarrhoea · volume of ORS solution needed · risk of diarrhoea worsening nutritional status Feeding older childrenChildren may have a poor appetite after antibiotic treatment, but this usually improves after 1 - 2 days. Children should be fed: · frequent small meals (‘little and often’) · their usual foods, which should not be diluted Image references ################ .\IMAGES\T45262.jpg Management - 8 Oral Antibiotics for the Treatment of Cholera1 (WHO 1995)Antibiotic Regimen Children Adults Preferred Doxycycline2 Single dose Not licensed 300 mg TetracyclineFour times per day 12.5 mg/kg 500 mg for 3 daysTrimethoprim (TMP)-Twice a day for TMP: 5 mg/kg 160 mg sulphamethoxazole 3 days SMX: 25 mg/kg 800 mg (SMX) Alternatives Erythromycin Four times per day12.5 mg/kg 250 mg for 3 days Furazolidone3 Four times per day1.25 mg/kg100 mg for 3 days 1. Oral antibiotics should be given when vomiting has subsided, usually after initial ORT. 2. Doxycycline is suitable only for children over 12 years.3. Furazolidone is the antibiotic of choice in pregnancy.Which factors affect the choice of antibiotic? Choice of antibioticFactors that affect the drug used to treat cholera include: · resistance of local strains to antibiotics · availability of antibiotics· cost of antibiotics · age of the patient · whether the patient is pregnant Image references ################ To return to the start of the section. A child aged 18 months presents with acute watery diarrhoea. He has some dehydration but this is not severe. What treatment would you choose? Click your mouse on a box below.Hold the mouse down and drag the box to the Treatment column.Treatment Management: AssessmentIntravenous rehydration Oral rehydration Breast feeding throughout diarrhoea Breast feeding after initial rehydration Antimicrobials againstV. cholerae O1 No antimicrobial drugs Loperamide to stop the diarrhoea No antidiarrhoeal drugs 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 ################ Summary Click on the buttons below for summary information. Picture: Intravenous rehydration for cholera.Aetiology Epidemiology PathophysiologyClinical Features andLaboratory Diagnosis Management Copyright Image from Centers for Disease Control and Prevention. Aetiology Acute watery diarrhoea worldwide each year causes: ·1.4 billion episodes - over 75% of all episodes of diarrhoea ·1.6 million deaths - 50% of all deaths from diarrhoea The major causes of acute watery diarrhoea in developing countries are: · rotavirus · enterotoxigenic E. coli · V. cholerae O1 Other causes include small round structured viruses, enteropathogenic E. coli, Campylobacter and non-typhoid Salmonella, and Cryptosporidium.Epidemiology Pathogen Geographical Seasonal Ages Main mode ofdistribution peak affected transmissionRotavirus Developed and Winter < 2 years Person todeveloping (in temperate (peak 6 - 12 person countries countries) months) ETEC Developing Warm Children and Contaminated countries,months adults water and food travellers EndemicDevelopingWarm 2 - 5 years Contaminated V. cholerae O1 countrieswater and food EpidemicDeveloping Children andContaminated V. cholerae O1 countriesadultswater and food PathophysiologyRotavirus causes acute watery diarrhoea by: 1. virus invading and damaging enterocytes in the small bowel 2. viral multiplication causing increased enterocyte shedding and proliferation 3. reduced absorption due to repopulating crypt like enterocytes, stunted villi and fall in disaccharidase activity ETEC and V. cholerae O1 cause acute watery diarrhoea by: 1. secretion of a soluble toxin taken up by the enterocyte 2. activation of adenylate cyclase, increasing intracellular cAMP levels 3. massive secretion of electrolytes and waterClinical Features and Laboratory Diagnosis Clinical features of acute watery diarrhoea include: · watery stools ranging from loose to extremely high volume · dehydration ranging from mild to severe · vomiting · abdominal cramps · fever in some cases Identification of the specific pathogen: · is not possible from clinical features - except for severe cholera · is not necessary for treatment · requires laboratory facilitiesManagement The key steps in treatment are: · prevent dehydration if there are no signs of dehydration · treat dehydration when it is present: - ORT for some dehydration - intravenous fluids for severe dehydration· breast feed throughout the diarrhoea episode · restart solid food after initial oral rehydration · give antibiotics if cholera is suspectedSection 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\T33079s.jpg You have now finished the tutorial Acute Watery Diarrhoeaã The Trustee of the Wellcome Trust, 1998 Further reading Further activities Restart tutorial Picture: Oocysts of Cryptosporidium, an important cause of watery diarrhoea in HIV-positive patients.Copyright Image from Centers for Disease Control and Prevention. Further reading Haffejee IE. The epidemiology of rotavirus infections: a global perspective. J Pediatr Gastroenterol Nutr 1995;20:275-86. Hart CA. Diarrhoea caused by viruses. In: Cook GC, ed. Manson’s tropical diseases. 20th ed. London: WB Saunders, 1996:730-5. Ingram CW, Wilson KH. Bacterial diarrheas. In: Rustgi VK, ed. Gastrointestinal infections in the tropics. Basel: Karger, 1990:206-23. Kaper JB, Morris JG Jr, Levine MM. Cholera. Clin Microbiol Rev 1995;8:48-86. Rolston DDK. The treatment of acute watery infectious diarrhea in the tropics. In: Rustgi VK, ed. Gastrointestinal infections in the tropics. Basel: Karger, 1990:224-41. Shears P. Cholera. Ann Trop Med Parasitol 1994;88:109-22. World Health Organization. The treatment of diarrhoea - a manual for physicians and other senior health workers. WHO/CDR/95.3. Geneva: WHO, 1995. Further activities To look at pictures related to this tutorial, search the image collection using the following keywords: · clinical features - type of diarrhoea - acute watery diarrhoea · disease name - bacterial diseases - cholera · disease name - viral diseases - human rotavirus infection · disease name - bacterial diseases - E. coli infection · diagnosis · treatment Image references ################ .\IMAGES\T39435s.jpg