Acute Bloody Diarrhoeaã The Trustee of the Wellcome Trust 1998Reviewed by: Professor B S Drašar, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine and Dr W A M Cutting, Department of Child Life and Health, The University of Edinburgh, UK Picture: A bloody stool from a patient with shigellosis.Copyright Image from Behrens RH.Image references ################ .\IMAGES\T25584.jpg Contents Click on the underlined text to jump tothat screen. Screen 3 Objectives 4Introduction 5Aetiology 11Assessment 12 Epidemiology 19Assessment 20 Pathophysiology25 Assessment 26 Clinical Features and LaboratoryDiagnosis 32 Assessment 33 Management 44 Assessment 45 Tutorial Assessment 46 Summary Underlined text is interactive. It indicates that further information is available. Click on the underlined text to view the information. Picture: A slum in Indonesia. Living conditions here favour the transmission of diarrhoeal diseases.Copyright Copyright Image from United Nations Children's Fund, India.Image references ################ .\IMAGES\T23718c.jpg Objectives At the end of this tutorial you should be able to: 1. name the main pathogens that cause acute bloody diarrhoea: · Shigella · Campylobacter jejuni· non-typhoid Salmonella· enteroinvasive E. coli · Entamoeba histolytica 2. describe the epidemiology of the key pathogens 3. summarize how the pathogens cause acute bloody diarrhoea 4. describe the clinical features of dysentery and the role of laboratory diagnosis5. review the management of a patient with acute bloody diarrhoeaImage 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 bloody diarrhoea.Picture: A stool from a patient with acute bloody diarrhoea. Copyright Image from Tubbs HR. 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\T22821.jpg AetiologyAetiology Image references ################ Aetiology - 1Impact of acute bloody diarrhoea Infectious diarrhoea presents as three clinical syndromes:· acute watery diarrhoea· dysentery or acute bloody diarrhoea· persistent diarrhoea In children under 5 years, acute bloody diarrhoea (see pie charts) causes: · 10% of all episodes of diarrhoea· 15% 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 Refer to the tutorial Diarrhoeal Diseases: Acute Watery Diarrhoea. 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 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 bloody diarrhoea The major causes of acute bloody diarrhoea in children (see pie chart) are: · Shigella · Campylobacter jejuni · non-typhoid SalmonellaLess · enteroinvasive Escherichia coliimportant · Entamoeba histolytica pathogens. (amoebic dysentery) Shigella C. jejuni Salmonella Enteroinvasive E. coli Entamoeba histolytica Pie chart: Causes of acute bloody diarrhoea in young children in developing countries. Data from Huilan et al 1991. Copyright Image from The Wellcome Trust modified from Huilan S, Zhen LG, Mathan MM. Bull World Health Organ 1991;69:549-55. Shigella Dysentery due to Shigella (bacillary dysentery or shigellosis) causes: · over 50% of all episodes of bloody diarrhoea · about 80% of all deaths from dysentery in children under 5C. jejuniData for C. jejuni probably include some cases of the related bacterium C. coli, as the two species are difficult to distinguish. Causes of dysenterySeveral of these pathogens can also cause acute watery diarrhoea.Image references ################ .\IMAGES\Abdaeto.gif Aetiology - 3ShigellaThe bacterium Shigella: · is a Gram-negative bacillus · is aerobic· is non-motile · has four pathogenic species: - S. dysenteriae Important in - S. flexnerideveloping countries. - S. boydii - S. sonnei Picture: A high power light micrograph taken from a culture of Shigella. Gram stain.Copyright Image from The Wellcome Trust. Species of Shigella Each of these species has up to 15 different serotypes. Image references ################ .\IMAGES\T3130.jpg Aetiology - 4Other causes of dysentery - 1 The bacterium C. jejuni (see picture) is: · a Gram-negative rod · S-shaped or spiral · thermotolerant · motile The bacterium non-typhoid Salmonella: · is a Gram-negative bacillus · is aerobic · is motile· has numerous serotypesPicture: C. jejuni (EM). The spiral bacterium has a flagellum at each end. Copyright Image from Skirrow MB, courtesy of Purdham DR. Non-typhoid SalmonellaThe nomenclature of the genus Salmonella is controversial. One classification scheme contains: · S. choleraesuis· S. typhimurium · S. enteritidis (numerousserotypes)· S. typhi - typhoid Salmonella Non-typhoid Salmonella.Image references ################ .\IMAGES\T45525.jpg Aetiology - 5Other causes of dysentery - 2 The bacterium enteroinvasive E. coli (EIEC) is: · a Gram-negative bacillus · non-motile · defined by its invasive pathogenesis The protozoan Entamoeba histolytica: · is a member of the phylum Sarcomastigophora · has a trophozoite and cyst as key stages in its life cycle (see pictures) · can cause: - invasive amoebiasis (amoebic dysentery) - asymptomatic luminal amoebiasis Pictures: A trophozoite and cyst of Entamoeba histolytica. Trophozoite Cyst Copyright Image from Liverpool School of Tropical Medicine photo by Stich A. Copyright Copyright holder unknown.Image from Rodhain F. In: Zaiman H. A Pictorial Presentation of Parasites 1986. Pathogenic E. coli There are five types of pathogenic E. coli, classified according to the mechanism by which they cause diarrhoea. The five types are: · enteroinvasive E. coli (EIEC) · enterohaemorrhagicE. coli (EHEC) · enterotoxigenic E. coli (ETEC)· enteropathogenic E. coli (EPEC) · enteroaggregative E. coli (EAggEC) Cause acute bloody diarrhoea.Image references ################ .\IMAGES\T25124c.jpg Aetiology: AssessmentAre the following statements about X true or false ? Click this button to return to the start of this section. Click on the True or False button for each statement. 1. The first statement, which can be true or false. T (11-pt bold yellow) 2. The second statement, which can be true or false.F 3.The third statement, which can be true or false.T Correct Text explaining the answer (11-pt plain blue) Incorrect Text explaining the answer (11-pt plain blue) Incorrect Text explaining the answer (11-pt plain blue) Correct Correct Incorrect Incorrect Correct Correct Incorrect Incorrect Correct Are the following statements about the aetiology of acute bloody diarrhoea true or false? To return to the start of the section. Click on the True or False button for each statement. 1. Acute bloody diarrhoea causes fewer episodes and deaths than acute watery diarrhoea worldwide.2. Acute bloody diarrhoea is most frequently caused by bacteria of the genus Shigella. 3. Dysentery can be caused by Campylobacter jejuni, non-typhoid Salmonella and enteroinvasive E. coli. 4. Entamoeba histolytica accounts for around 15% of all cases of childhood dysentery in developing countries. Correct Acute bloody diarrhoea causes fewer deaths than acute watery diarrhoea from dehydration. However, dysentery is a more significant factor in causing malnutrition. Incorrect Text 11 pt Arial dark blue goes here Incorrect Acute bloody diarrhoea causes fewer deaths than acute watery diarrhoea from dehydration. However, dysentery is a more significant factor in causing malnutrition. Correct Text 11 pt Arial dark blue goes here Correct Shigella causes: · over 50% of episodes of acute bloody diarrhoea · about 80% of deaths from dysentery in children under 5 years Incorrect Incorrect Shigella causes: · over 50% of episodes of acute bloody diarrhoea · about 80% of deaths from dysentery in children under 5 years Correct Correct These pathogens are less important globally than Shigella. Incorrect Incorrect These pathogens are less important globally than Shigella. Correct Correct Incorrect Entamoeba histolytica causes about 2% of cases of dysentery in children. Incorrect Correct Entamoeba histolytica causes about 2% of cases of dysentery in children. Image references ################ Epidemiology EpidemiologyImage references ################ Epidemiology - 1Endemic shigellosis Most of the deaths from shigellosis worldwide are from endemic disease. Diarrhoea due to endemic Shigella: · is important in many developing countries · occurs all year round · peaks in the hot season · affects mainly children aged6 months to 3 years No. isolated per1000 Shigella sp. S. dysenteriae S. flexneri WinterHot summer Monsoon Winter Graph: The seasonal pattern of endemic shigellosis in Bangladesh. Data from Stoll et al 1982. 1980 Copyright Image from The Wellcome Trust modified from Stoll BJ, Glass RI, Huq MI, Khan MU, Banu H, Holt J. J Infect Dis 1982;146:177-83. Endemic shigellosisEndemic shigellosis in developing countries is caused: · prinicipally by S. flexneri· less commonly by S. dysenteriae · by a wide range of serotypes in each endemic area Peak in the hot seasonEndemic shigellosis in Bangladesh (see graph) shows a second peak in the cooler winter months. Age affected This peak in young children largely reflects: · the introduction of faecally contaminated solid food and liquids at weaning · greater exposure to pathogens through: - crawling and walking - putting objects in the mouth · poorly developed defence mechanisms Image references ################ .\IMAGES\Shigendi.gif Epidemiology - 2 Epidemic shigellosisEpidemics due to Shigella: · are usually caused by S. dysenteriae type 1 · affect children and adults · are a risk for most developing countries · generally cause a peak number of cases in the hot season Picture: Emergency supplies of water being brought to Rwandan refugees in Zaire. Refugees are at high risk of diarrhoeal diseases such as shigellosis.Copyright Copyright holder unknown. Image supplied by MERLIN picture library. S. dysenteriae type 1S. dysenteriae type 1 is the only pathogen that causes large scale epidemics of dysentery. Peak in the hot season This seasonal peak is less pronounced in Africa.Children and adults affected Refugees may be particularly susceptible. In Goma, Zaire, in July 1994: · there was an epidemic of S. dysenteriae type 1· an estimated 30,000 Rwandan refugees died from shigellosis Image references ################ .\IMAGES\T45822.jpg Epidemiology - 3 Peak age Major endemicPathogen of infection areas Bacteria C. jejuni1 Children aged Worldwide1 - 2 years Non-typhoid Children Worldwide Salmonella EIEC Children Uncommon in developed andand adults developing countries Protozoa EntamoebaAdults2 Central and South America,histolyticasub-Saharan Africa, South AsiaOther Causes of Dysentery 1. Cases of C. jejuni probably include C. coli. 2. Amoebic dysentery is uncommon in children under 3 years.Image references ################ Food Drinking water Person to person Faecal contaminationof hands and clothes Contaminated with faeces Endogenous pathogens Contact, fingers putin mouth Not cooked thoroughly Epidemiology - 4 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 Which factors favour transmission of diarrhoea? Picture: Modes of faecal-oral transmission. 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 - 5Transmission of Shigella Transmission of shigellosis is by: · direct person to person contact · faecally contaminated food and water · fomites, eg. dirty towels Shigellosis is particularly associated (see picture) with: · crowded living conditions · insufficient safe water · poor sanitation Picture: A slum in Calcutta, India. Overcrowding, poor sanitation and preparation of food in a dirty environment all favour the transmission of shigellosis here. Copyright Image from Tomkins AM. Person to person spreadDirect person to person transmission: · occurs through faecal contamination of hands · is often within a family, eg. from mother to child · is favoured by the low infective dose of Shigella - fewer than 100 bacteria Image references ################ .\IMAGES\T25658.jpg Epidemiology - 6Transmission of Other Causes of Dysentery Pathogen Major modes of transmission C. jejuni1 Person to person Contaminated food, eg. chicken, milk From animal reservoirs, eg. poultry Non-typhoid Contaminated food (meat, poultry or Salmonella eggs), unpasteurized milk From animal reservoirs, eg. poultry EIEC Contaminated food, eg. cheeses Entamoeba histolytica Person to person Food and water contaminated with cysts 1. Probably includes C. coli, which is transmitted through contaminated pork. Image references ################ Epidemiology: AssessmentThe table summarizes the epidemiology of acute bloody 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 affectedMajor modes of transmission EndemicChildren of 6 - 36 monthsShigellaPerson to person Faecally contaminated food Epidemic Fomites Shigella C. jejuni Children of 1 - 2 years Entamoebahistolytica Person to person Faecally contaminated food and water To return to the start of the section. Children and adults Person to person Contaminated food AdultsImage references ################ PathophysiologyPathophysiology Image references ################ Pathophysiology - 1 The 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 bloody diarrhoea is generally of an 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) is watery. In 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 diarrhoea Invasive diarrhoea Osmotic 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. Acute bloody diarrhoea The bacteria that cause dysentery (eg. Shigella, C. jejuni) can also produce watery diarrhoea. These bacteria cause: · acute bloody diarrhoea by an inflammatory invasive mechanism · acute watery diarrhoea by a secretory mechanism Image references ################ .\IMAGES\Diarmech.gif Pathophysiology - 2Pathophysiology of inflammatory invasive diarrhoea 1. Invasive bacteria infect epithelial cells of the distal small bowel and colon. 2. Bacteria multiply within mucosal cells and spread between cells, killing them. 3. Extensive inflammatory damage is caused to the mucosa. An acute bloody diarrhoea results, caused by: · reduced absorption of the damaged mucosa · exudation of fluid from the mucosa Picture: Shigella invading cultured cells (TEM). Copyright Image from Sansonetti PJ. Killing of mucosal cellsCell death is generally caused by cytotoxins. Image references ################ .\IMAGES\T45955.jpg Pathophysiology - 3Gross mucosal damage due to invasive bacteria Invasive bacteria typically cause extensive damage to the bowel. This includes: · mucosal inflammation and erosion (see picture) · mucosal ulceration· formation of microabscesses· production of exudate containing blood, mucus and pus These histological changes occur to varying degrees in infection by: · Shigella· C. jejuni · non-typhoid Salmonella · EIEC Picture: Haemorrhagic colitis due to Shigella in the Rhesus monkey.What happens in invasive amoebiasis? Copyright Image from Centers for Disease Control and Prevention. Exudate This inflammatory exudate causes the characteristic bloody mucoid stool. Non-typhoid SalmonellaPicture: Salmonella typhimurium (S) inside a vacuole of an infected intestinal cell. Note the local disruption (D) of microvilli.Image from Finlay B. D S Non-typhoid Salmonella: · causes only mild changes to the epithelium · invades and inflames the lamina propria · can enter the blood and spread systemically Invasive amoebiasisPicture: The colonic mucosa of a patient with amoebic dysentery. Note the ulceration through the muscularis mucosa. Image from The Wellcome Trust courtesy of Wenyon CM. The protozoan Entamoeba histolytica is not strictly invasive. It: 1. adheres to cells of the colon 2. produces cytotoxins to kill colonocytes 3. phagocytoses colonocytes and red blood cells 4. leads to flask-shaped ulceration of the colonic mucosa (see picture) Image references ################ .\IMAGES\T33790.jpg .\IMAGES\T45846p.jpg .\IMAGES\T3612p.jpg Pathophysiology - 4 Toxins produced by invasive bacteria Invasive bacteria secrete a wide range of toxins, which can: · contribute to diarrhoea · cause extraintestinal complications The most important extraintestinal complication is haemolytic-uraemic syndrome (HUS). This syndrome: · consists of acute renal failure, haemolytic anaemia and thrombocytopenia · is restricted to S. dysenteriae type 1 (Shiga toxin) and EHEC (Shiga like toxins or SLTs)Picture: Urine from a patient with diarrhoea complicated by haemolytic-uraemic syndrome. The red colour indicates haemoglobin from haemolysis.Copyright Image from Tubbs HR. Toxins in diarrhoeaToxins contribute to diarrhoea in two main ways. 1. Cytotoxins kill enterocytes and colonocytes, causing bloody diarrhoea. 2. Enterotoxins disturb electrolyte flux, causing watery diarrhoea. Shiga toxin Shiga toxin and SLTs are: · cytotoxic, enterotoxic and neurotoxic · inhibitors of protein synthesis EHECEHEC includes E. coli O157:H7. Image references ################ .\IMAGES\T22918.jpg Pathophysiology: AssessmentThe picture shows inflammatory damage to the small bowel caused by an invasive pathogen. Note the deep crypts and loss of villi. This pathogen: · is the second most common cause of dysentery worldwide · can cause watery or bloody diarrhoea · does not usually cause extraintestinal complications What is the pathogen? Type your answer and then press Enter To return to the start of the section.Copyright Image from Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto courtesy of Luk SC. Correct Yes. That’s right. The correct answer is Campylobacter jejuni.The answer is ....................... Explanation..... Wrong again. The answer is ................ Explanation .................... You may want to revise this section (click Revise button). Incorrect No. That’s not right. The correct answer is Campylobacter jejuni. Image references ################ .\IMAGES\T14925.jpg Clinical Features and Laboratory Diagnosis Clinical Features and Laboratory DiagnosisImage references ################ Clinical Features and Laboratory Diagnosis - 1 Diarrhoea due to Shigella Infection Species Typical clinical effectsS. dysenteriae1 Likely to cause severe dysentery S. flexneri1 Can cause severe dysentery S. boydii Cause relatively mild waterydiarrhoea or (less often) S. sonnei bloody diarrhoea 1. These are the most important species in developing countries. Shigella infection The clinical effects of Shigella infection vary (see table) from: · mild self-limited watery diarrhoea to · severe bloody diarrhoea (bacillary dysentery) causing death in a few days Watery diarrhoea: · is seen in up to 50% of patients · can develop into bacillary dysentery after 1 - 2 daysImage references ################ Clinical Features and Laboratory Diagnosis - 2Clinical features of bacillary dysentery Bacillary dysentery can cause: · frequent stools with visible blood and mucus (see picture) · fever · rectal pain on defaecation · abdominal cramps · anorexia · dehydration · febrile convulsions · intestinal and extraintestinal complications How long do symptoms last? Picture: A stool from a patient with shigellosis.Copyright Image from Bennish M. Frequent stoolsStools can be: · of small volume · passed 30 - 100 times per day Rectal painPain on defaecation or attempted defaecation is called tenesmus.Duration of symptomsBacillary dysentery typically: · has an incubation period of1 - 5 days· if untreated lasts 2 - 10 days, when it is not fatal Image references ################ .\IMAGES\T45899.jpg Clinical Features and Laboratory Diagnosis - 3 Complications of Bacillary Dysentery Intestinal and nutritional Extraintestinal complications complicationsWeight loss and falling Bacteraemia nutritional status HyponatraemiaRectal prolapse Hypoglycaemia Intestinal perforation Haemolytic-uraemic syndromeToxic megacolon Secondary infection, eg. pneumoniaWho is at risk of complications? Weight loss and malnutritionThese reflect: · anorexia · increased catabolism · reduced digestion and absorption · protein losing enteropathyHUSHUS: · is restricted to S. dysenteriae type 1 · can develop 7 - 10 days after the onset of diarrhoea Who is at risk?Complications of shigellosis are most common in children:· under 12 months of age· with severe malnutrition · who have had measles in the past 6 weeks Also at risk of complications are: · children with severe dysentery · patients with dehydration · patients not given antibiotics promptly · adults aged over 50 years Hypoglycaemia and hyponatraemiaPicture: A child withS. dysenteriae type 1 infection undergoing a convulsion due to hypoglycaemia. Image from Bennish M. Hypoglycaemia (low blood glucose) and hyponatraemia (low blood sodium) are restricted to: · S. dysenteriae · S. flexneri Rectal prolapse Image from International Centre for DiarrhoealDisease Research, Bangladesh. The picture shows a Bangladeshi child with rectal prolapse secondary to infection with S. dysenteriae type 1. Toxic megacolon Picture: The abdomen of a Bangladeshi child with toxic megacolon. Image from Bennish M. The child pictured was infected with S. dysenteriae type 1. Note the outlines of distended loops of colon.Image references ################ .\IMAGES\T45901p.jpg .\IMAGES\T45897p.jpg .\IMAGES\T45898p.jpg Clinical Features and Laboratory Diagnosis - 4Clinical features of other types of dysentery The other pathogens (see table) cause dysentery similar to shigellosis but the: · symptoms are generally milder · complications seen in shigellosis are rarer How helpful are these differences fordiagnosis? Clinical Features of Dysentery not due to Shigella Pathogen Differences from bacillary dysenteryC. jejuni1 Acute watery diarrhoea in two-thirds ofcases EIEC1 Watery diarrhoea more common thandysentery Non-typhoid Watery diarrhoea more common than Salmonella1 dysentery Entamoeba histolytica Gradual onset over 2 - 3 weeks Fever in under 50% of cases Can spread to cause liver abscesses 1. Most bacterial episodes resolve in 2 - 5 days.Clinical featuresThe exception to both of these generalizations is enterohaemorrhagic E. coli O157:H7, which has caused important outbreaks. How helpful are differences? The clinical features shown are not sufficient to: ·identify the specific pathogen·distinguish shigellosis from other forms of dysenteryImage references ################ Clinical Features and Laboratory Diagnosis - 5Laboratory diagnosis Laboratory methods to support clinical diagnosis include: · microscopic examination of the stool for: - polymorphonuclear neutrophils (PMNs) - Entamoeba histolytica trophozoites · culture of bacteria from a stool sample (see picture)When is determination of the specific pathogen necessary? Picture: Growth of Shigella on selective culture medium.Copyright Image from Ridgway GL. PMNsA finding of numerous PMNs in the stool: · confirms that there is colonic inflammation · does not identify the pathogen · provides little information that cannot be obtained clinically Culture of a stool sample This is the definitive technique to identify bacterial pathogens, but: · can take 2 - 3 days, too long to delay treatment · requires a fresh stool sample Entamoeba trophozoitesMicroscopic diagnosis of invasive amoebiasis relies on finding trophozoites that contain ingested red blood cells.Aetiological diagnosisIdentification of the pathogen causing dysentery is: · generally not possible from clinical features · required: - for epidemiological surveillance - to determine antibiotic sensitivity Identification for surveillance and antibiotic resistance testing is carried out at a reference laboratory. Image references ################ .\IMAGES\T45566.jpg Clinical Features and Laboratory Diagnosis: AssessmentAre the following statements about X true or false ? Click this button to return to the start of this section. Click on the True or False button for each statement. 1. The first statement, which can be true or false. T (11-pt bold yellow) 2. The second statement, which can be true or false.F 3.The third statement, which can be true or false.T Correct Text explaining the answer (11-pt plain blue) Incorrect Text explaining the answer (11-pt plain blue) Incorrect Text explaining the answer (11-pt plain blue) Correct Correct Incorrect Incorrect Correct Correct Incorrect Incorrect Correct Are the following statements about shigellosis true or false?Click on the True or False button for each statement. The clinical features of bacillary dysentery generally include: To return to the start of the section. 1. a foul smelling stool2. fever3. anorexia4. gradual onset over 2 - 3 weeksCorrect Text explaining the answer (11-pt plain blue) Incorrect A foul smelling stool is not a feature of shigellosis.Incorrect Correct A foul smelling stool is not a feature of shigellosis.Correct Most patients with shigellosis are febrile.Incorrect Incorrect Most patients with shigellosis are febrile.Correct Correct Anorexia is common in patients with shigellosis.Incorrect Incorrect Anorexia is common in patients with shigellosis.Correct Correct Incorrect Bacillary dysentery has a rapid onset over a few days. Onset over 2 - 3 weeks is more typical of amoebic dysentery.Incorrect Correct Bacillary dysentery has a rapid onset over a few days. Onset over 2 - 3 weeks is more typical of amoebic dysentery. Image references ################ Management Management Image references ################ Management - 1Assessing a child with diarrhoea Clinical examination and a brief history should follow these steps. 1. Assess the degree of dehydration. 2. Establish whether diarrhoea is watery or bloody (see picture). 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 bedpan containing a semiformed stool with blood and mucus. This stool is from a patient with amoebic dysentery. Copyright Image from Tubbs HR. Immunization historyEvery opportunity to check immunization status should be taken. In particular, measles is: · 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 days Image references ################ .\IMAGES\T22834.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 For related tutorials. In contrast to acute watery diarrhoea, acute bloody diarrhoea does not often lead to severe dehydration. Picture: Assessment of the degree of dehydration by a skin pinch test. The skin pinch in this child returned slowly but not very slowly, indicating some but not severe dehydration.Copyright Image from United Nations Children's Fund, India. Related tutorialsRefer to the tutorial Diarrhoeal Diseases: Clinical Assessment. Dehydration in dysenteryAlthough severe dehydration is uncommon in acute bloody diarrhoea, patients with any degree of dehydration and dysentery are at increased risk of complications and death. Image references ################ .\IMAGES\T23157.jpg Management - 3Clinical diagnosis of acute bloody diarrhoea Acute bloody diarrhoea (dysentery) is diagnosed clinically by: · loose or watery stools that contain visible red blood or · a history of bloody stools reported by the child’s mother In either case the presumptive diagnosis is shigellosis. Why is this the diagnosis? Picture: A bloody mucoid stool from a patient with bacillary dysentery.Copyright Image from Behrens RH. Visible red bloodThis diagnosis excludes: · streaks of blood on the surface of a formed stool · blood detected only microscopically or biochemically · black stools containing digested blood (melaena) Mucus and pus may be present but are not necessary for a diagnosis. Presumptive diagnosisA presumptive diagnosis is necessary because clinical features do not identify the pathogen. Shigellosis is the presumptive diagnosis because it: ·is the most common cause of acute bloody diarrhoea (see screen 7) · can cause complications and death if not treated · can be cured by early appropriate antibiotic therapy Image references ################ .\IMAGES\T25584.jpg Management - 4Treatment of a child with acute bloody diarrhoea In a child with acute bloody diarrhoea, the key steps in treatment are: 1. refer patients at high risk to hospital 2. treat dehydration, usually by oral rehydration 3. give an oral antibiotic effective against Shigella for 5 days 4. feed frequently, including continued breast feeding 5. follow the patient up after 2 days 6. do not give antidiarrhoeal drugs, eg. loperamide What are the common errors made in management?High-risk children Children to refer are those with: · severe malnutrition · severe dehydration· age under 12 months· measles in the past 6 weeks Antibiotics against Shigella Antibiotic treatment: · follows from the presumptive diagnosis of shigellosis · must be started promptly ErrorsThe treatment of patients with bloody diarrhoea is often poor. Common errors include: · prescribing medications that are ineffective or dangerous · giving drugs in doses that are too low and regimens that are too short· failing to give adequate oral rehydration therapy · wrongly reducing or withholding food Image references ################ Management - 5 Management of Dehydration (WHO 1995) Degree of dehydration Treatment No signs of dehydration1 Extra oral fluids athome to preventdehydration andmalnutrition Some dehydration2Oral rehydrationtreatment with ORS solution in ahealth facility Severe dehydrationIntravenousrehydration in hospitalPrevention and treatment of dehydration Treatment should reflect the degree of dehydration (see table). For related tutorials. 1. Feeding, including breast feeding, should be continued throughout the diarrhoea episode. 2. Breast feeding should be given during rehydration, and solid food restarted after 4 - 6hours of oral rehydration. Extra home fluids More fluids than normal should be given, including: · salted drinks · vegetable or chicken soup with saltORS solution Oral rehydration salts (ORS) solution: · is a solution of salts and glucose of a defined composition · contains electrolytes in concentrations similar to those in a watery stool Related tutorials For details refer to the Diarrhoeal Diseases tutorials: · Clinical Assessment · Rehydration and Early Feeding Image references ################ Management - 6Antibiotics for the Treatment of Shigellosis (WHO 1994) Drug Resistance1 Comments Ampicillin Most S. dysenteriae type 1; Cheap and widely available many other Shigella species Trimethoprim- Many S. dysenteriae type 1; Cheap and widely available sulphamethoxazole variable among other Shigella species Nalidixic acid Increasing among S. dysenteriaeCheap but of variable availability type 1; uncommon among other Shigella species Pivmecillinam Rare among all Shigella species Expensive and of limited availability Fluoroquinolones2 Rare among all Shigella species Expensive and of variable availability Ceftriaxone Rare among all Shigella species Expensive and of limited availability 1. Shigella is usually also resistant to metronidazole, streptomycin, tetracyclines, chloramphenicol and sulphonamides. Shigellosis is not usually effectively treated with any of these antibiotics. 2. These drugs (ciprofloxacin, norfloxacin and enoxacin) are not approved for use in children under 15 years. Choice of antibioticFactors that affect the drug used to treat shigellosis include: · resistance of local strains to antibiotics. This is: - a growing problem - most common in S. dysenteriae type 1 - often transmitted by plasmids · availability · cost · age of the patient Image references ################ Management - 7Antibiotic Regimens for the Treatment of Shigellosis (WHO 1994)1 Children Adults Drug DoseFrequencyDoseFrequency Ampicillin25 mg/kg4 times a day 1 g4 times a day Trimethoprim- TMP: 5 mg/kg Twice160 mg Twicesulphamethoxazole SMX: 25 mg/kga day 800 mga day (TMP-SMX) Nalidixic acid 15 mg/kg 4 times a day 1 g4 times a day Pivmecillinam 20 mg/kg 4 times a day 400 mg4 times a day FluoroquinolonesNot licensed for use2 Vary with different drugs Ceftriaxone320 mg/kgTwice a day 1 g Once a day 1.The duration of treatment in all cases is 5 days. 2. Fluoroquinolones are not yet approved as they cause arthropathy in young experimental animals. 3. Intravenous therapy. All the other drugs shown are given orally. Image references ################ Management - 8Follow-up after antibiotic treatment for shigellosis An effective antibiotic produces marked clinical improvement within 2 days. If there is no definite improvement after this time, the child should be given a different antibiotic against Shigella. If this second antibiotic does not work after 2 days the child should be: · referred to hospital or · treated for amoebiasis (see screen 42) Loose bloody stools Refer to hospital Severe malnutrition? YesYesYesYes NoNo NoNo Antibiotic against Shigella Complete 5 days of treatment Better in 2 days? Initially dehydrated, age < 1yearor measles in past 6 weeks? Refer to hospital Different antibiotic against Shigella Complete 5 days of treatment Better in 2 days? Refer to hospital or treat Flow chart: Outpatient management of acute bloody diarrhoea in children under 5 years.for amoebiasis Copyright Image from The Wellcome Trust modified from World Health Organization. The treatment of diarrhoea - a manual for physicians and other senior health workers. WHO/CDR/95.3. Geneva: WHO, 1995.Clinical improvementWithin 48 hours there should be improvement in: · fever · stool frequency · blood in the stool · abdominal pain· appetite Children who are improving must still complete the5 day course of antibiotics. Referral to hospitalHospitalization allows: · more specialist treatment · identification of the pathogen, depending on laboratory facilities available Image references ################ .\IMAGES\Abdflow.gif Management - 9 Antimicrobial Therapy for Amoebic Dysentery (WHO 1994)1 Drug Dose Regimen Children Metronidazole 10 mg/kg 3 times a day for 5 daysAdults Metronidazole 750 mg3 times a day for 5 days1. The duration of treatment is 10 days for severe disease. Antiparasitic drugs for amoebic dysentery Indications for drug treatment for amoebic dysentery (see table) are the: · detection of Entamoeba histolytica trophozoites, containing red blood cells, in a fresh stool sampleor · clinical failure of two different antibiotics against Shigella Entamoeba histolytica is the only dysentery pathogen, other than Shigella, for which antimicrobialsare indicated. Entamoeba histolytica trophozoitesPicture: A trophozoite of Entamoeba histolytica.Image from London School of Hygiene and Tropical Medicine. The trophozoite shown has ingested red blood cells. This finding is an indication for giving drugs against invasive amoebiasis. Failure of two antibiotics The two antibiotics must be known to be effective against local strains of Shigella, so that drug resistant Shigella can be ruled out as a cause of treatment failure. Image references ################ .\IMAGES\T22836p.jpg Management - 10 Nutrition in acute bloody diarrhoea Dysentery 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. 2. Older children should be given solid food after 4 - 6 hours of oral rehydration (see picture). 3. An extra daily meal should be given for at least 2 weeks after treatment. Picture: A child eating solid food after initial rehydration for acute diarrhoea.Copyright Image from United Nations Children's Fund, India. Diarrhoea and malnutritionDysentery contributes to falling nutritional status through: · anorexia· increased catabolism · reduced digestion and absorption · protein losing enteropathy 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 · shortens the duration of the episodeFeeding 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\T45965.jpg You are a health worker in Cameroon. Which drugs would you use to treat the children described below? Click your mouse on the correct drug tablet.Hold the mouse down and drag the tablet to the child. To return to the start of the section. Patient 1 drugs Patient 2 drugs · Patient 1 - has had a bloody mucoid stool for 5 days. · Patient 2 - who has had a microscopic diagnosis of amoebic dysentery.Management: AssessmentAmpicillin Chloramphenicol Nalidixic acid Metronidazole TMP-SMX Ampicillin Chloramphenicol Nalidixic acid Metronidazole TMP-SMX {feedback_var} Ampicillin Chloramphenicol Nalidixic acid Metronidazole TMP-SMX Ampicillin Chloramphenicol Nalidixic acid Metronidazole TMP-SMXImage references ################ .\IMAGES\Toddler1.gif .\IMAGES\Toddler2.gif .\IMAGES\pill1.gif .\IMAGES\pill2.gif .\IMAGES\pill3.gif .\IMAGES\pill4.gif .\IMAGES\pill5.gif .\IMAGES\pill1.gif .\IMAGES\pill2.gif .\IMAGES\pill3.gif .\IMAGES\pill4.gif .\IMAGES\pill5.gif Tutorial AssessmentAre the following statements about X true or false ? Click this button to return to the start of this section. Click on the True or False button for each statement. 1. The first statement, which can be true or false. T (11-pt bold yellow) 2. The second statement, which can be true or false.F 3.The third statement, which can be true or false.T Correct Text explaining the answer (11-pt plain blue) Incorrect Text explaining the answer (11-pt plain blue) Incorrect Text explaining the answer (11-pt plain blue) Correct Correct Incorrect Incorrect Correct Correct Incorrect Incorrect Correct Are the following statements true or false?Click on the True or False button for each statement. To return to the start of the tutorial. S. dysenteriae:1. is the only species of Shigella that causes acute bloody diarrhoea2. is not a significant cause of large scale dysentery epidemics3. can cause frequent bloody mucoid stools, fever, convulsions and dehydration4. must be managed by prompt effective antibiotic therapy and good feeding practiceCorrect Text explaining the answer (11-pt plain blue) Incorrect Shigellosis is caused by four species of Shigella: · S. dysenteriae* · S. flexneri* · S. boydii · S. sonnei *These species most commonly cause acute bloody diarrhoea. Incorrect Correct Shigellosis is caused by four species of Shigella: · S. dysenteriae* · S. flexneri* · S. boydii · S. sonnei *These species most commonly cause acute bloody diarrhoea. Correct Text 11 pt Arial dark blue goes here Incorrect S. dysenteriae type 1 is the only pathogen that causes epidemics of bloody diarrhoea on a wide scale. Incorrect Text 11 pt Arial dark blue goes here Correct S. dysenteriae type 1 is the only pathogen that causes epidemics of bloody diarrhoea on a wide scale. Correct Bacillary dysentery: · can have all of these clinical features · can also be complicated, eg. by HUS · is most often due to S. dysenteriae or S. flexneri Incorrect Incorrect Bacillary dysentery: · can have all of these clinical features · can also be complicated, eg. by HUS · is most often due to S. dysenteriae or S. flexneri Correct Correct Management of shigellosis is based on: 1. rehydration, eg. with ORS solution 2. antibiotic therapy, eg. with nalidixic acid 3. appropriate nutritional management 4. avoiding antidiarrhoeal drugs, eg. loperamide Incorrect Text 11 pt Arial dark blue goes here Incorrect Management of shigellosis is based on: 1. rehydration, eg. with ORS solution 2. antibiotic therapy, eg. with nalidixic acid 3. appropriate nutritional management 4. avoiding antidiarrhoeal drugs, eg. loperamide Correct Text 11 pt Arial dark blue goes hereImage references ################ Summary Click on the buttons below for summary information. Picture: A child with hypoglycaemia due to shigellosis. Aetiology Epidemiology Pathophysiology Clinical Features andLaboratory Diagnosis ManagementCopyright Image from Bennish M. Aetiology Acute bloody diarrhoea (dysentery) worldwide each year causes: ·200 million episodes - 10% of all episodes of diarrhoea ·480,000 deaths - 15% of all deaths from diarrhoea The major causes of acute bloody diarrhoea in developing countries are: · Shigella - causing shigellosis (bacillary dysentery) · Campylobacter jejuni · non-typhoid Salmonella · enteroinvasive Escherichia coli · Entamoeba histolytica - causing amoebic dysenteryEpidemiologyPathogen DistributionAgesTransmission Shigella Endemic Developing 6 - 36 months Person to personcountriesFaecally contaminated food EpidemicDeveloping Children and Fomitescountries adults C. jejuni Worldwide 1-2 years Person to personContaminated food (‘food poisoning’) Non-typhoidWorldwide ChildrenContaminatedSalmonellafood (‘food poisoning’) EIEC UncommonChildren and Contaminatedadults food (‘food poisoning’) Entamoeba Developing Adults Person to person histolytica countries Faecally contaminated food and waterPathophysiologyAcute bloody diarrhoea is caused by: 1. invasion of enterocytes and colonocytes by the pathogen2. multiplication of the pathogen within the mucosa 3. killing of mucosal cells by cytotoxins Histological damage includes: · mucosal inflammation, erosion and ulceration · formation of microabscesses· exudate containing blood, mucus and pus in the diarrhoea stools Toxins from invasive bacteria: · contribute to diarrhoea · cause extraintestinal complications Clinical Features and Laboratory DiagnosisClinical features of shigellosis (bacillary dysentery) are: · frequent small bloody mucoid stool · fever· abdominal cramps and tenesmus· anorexia and dehydration · complications, eg. HUS In other types of dysentery: · symptoms are milder and complications rarer than in shigellosis · onset is more gradual in amoebic dysentery Laboratory diagnosis of a stool sample includes: · microscopy for PMNs and Entamoeba histolytica trophozoites · culture of the pathogen ManagementBloody diarrhoea is: · diagnosed from visible red blood in the stool · most often due to shigellosis To treat shigellosis: 1. refer patients at high risk2. treat dehydration 3. give appropriate antibiotics for 5 days 4. maintain feeding 5. follow up after 2 days To treat amoebic dysentery give metronidazole for 5 days if: · the stool contains E. histolytica trophozoites with ingested red cells or · two different antibiotics for Shigella have failed Section 6 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 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\T45901.jpg You have now finished the tutorial Acute Bloody Diarrhoeaã The Trustee of the Wellcome Trust, 1998 Further reading Further activities Restart tutorial Picture: Preparing raw chicken next to food which is not cooked before eating can transmit Campylobacter and Salmonella. Copyright Image from Skirrow MB. Further reading Keusch GT, Bennish ML. Shigellosis: recent progress, persisting problems and research issues. Pediatr Infect Dis J 1989;8:713-9. Shears P. Shigella infections. Ann Trop Med Parasitol 1996;90:105-14. Stoll BJ, Glass RI, Huq MI, Khan MU, Banu H, Holt J. Epidemiologic and clinical features of patients infected with Shigella who attended a diarrhoeal diseases hospital in Bangladesh. J Infect Dis 1982;146:177-83. World Health Organization. The management of bloody diarrhoea in young children. WHO/CDD/94.49. Geneva: WHO, 1994.Further activities To look at pictures related to this tutorial, search the image collection using the following keywords: · clinical features - type of diarrhoea - bloody diarrhoea · disease name - parasitic diseases - amoebiasis · disease name - bacterial diseases - Campylobacter infection · disease name - bacterial diseases - shigellosis · diagnosis · treatment Image references ################ .\IMAGES\T45532.jpg