Gastroinestinal diseases

• gastroenteritis

• major disease burden

• infant death

• faecal - oral route

Viral diarrhoea

• non-enveloped double stranded RNA

• severe diarrhoea in infants and children

• capsid glycoprotein - VP7 and VP4 - immune targets

• G1 to G4, G9 most common

• very stable - viable for weeks or months

• facecal oral route transmission

Rotavirus

• replicates in small intestine epithelium

• viraemia - uncommon

• spread outside intestine

• isotonic diarrhoea

• recurrent infection - protective immunity but milder than first time

Rotavirus pathogenesis

• dehydrating gastroenteritis

• short incubation period - 2 days

• abrupt symtpms

• vomiting before diarrhoea

• asymptomatic to severe dehydrating diarrhoea - fever and vomiting

• hospitialisation

• GI symptoms resolve 3 to 7 days

Rotavirus clinical features

• effects children below the age of 5

• many required emergency department visits and many hospitalisation

• one death per year

• introduction of vaccine - decline in hospitalisation and emergency visits

• causing more issues than was realised

Rotavirus epidemiology

• two oral live attenuated vaccines

• Rotarix - GSK - one atteunated strain for rotarvirus G1P1A - protects against non-G1 serotypes

• RotaTeq - contains 5 human-bovin rotavirus re-assortants with human serotypes from G1-G4 and P1A8 and bovine serotypes g6 and p7

Rotavirus vaccination

• liver inflammation

• viral, bacterial or protozoal disease, toxins

• fever, GI issues, nausea and vomiting, jaundice and enlarged liver

• Jaundice - inability of the liver to eliminate bilirubin - deposited in the skin giving it a yellow hue

• all forms are genetically linked

• distinguished by serology - plasma analysis

• B,C,D - chronic hepatitis and cirrhosis and liver cancer - viral proteins may play a role in development of hepatocellular cancer

Hepatitis

• short incubation

• infectious

• picornavirus - small RNA

• single stranded RNA, no envelope

• one serotype

• heat and acid stable

• destroyed by autoclaving (high pressure sterilisation) UV, formalin or chloride

Hepatitis A

• mild in children or subclinical, uncommon jaundice, flu like symptoms, runny nose, lethargy, anorexia, diarrhoea

• adults - can have jaudince but less common, rarely give rise to fulminant hepatitis - massive liver tissue necrosis, post hepatits - weakness, lethargy, alcohol intolerance, prolonged jaudince

• no chronic liver disease

Hepatitis A clinical features

• faecal-oral route - contaminated food and water

• poor enviromental sanitation and hygiene - highly endemic

• Aboriginal community in NT

• universal infection early in life - most infections are asymptomatic

• infected by travel

Hepatitis A - transmission and epidemology

• inactivated virus

• virus grown from human cell cultures

• purified inactivated by formaldehyde and absorbed into aluminium hydroxide - adjuvant

• can be by itself or in combination

• recommended for Aboriginals and travellers who are going to endemic regions

• Vivaxim - combined with typhoid vaccine

Hepatitis A vaccine

• Hepadnavirus

• circular double stranded DNA

• enveloped

• many antigenic components

• humans are host

• infect for more than a week at room temp

• millions worldwide chronically infected

• cancer causing

Hepatitis B

• incubation for 120 days

• nonspecific prodromal (early warning signs) - malaise, fever, headache, myalgia

• infectious and asymptomatic half of the time

• complications - fulminant hepatiti, hospitalisation - weeks to months

• cirrhosis, hepatocellular carinoma, higher risk with early infection, asymptomatic but infectious

• adults - symptomatic acute hepatitis, chronically infected

• children - asymptomatic, infants can become chronic via mother and ages 1-5 years become chronically infected

• chronic adult and children hep b - die from cancer or cirrhosis, more children die

Hepatitis B clinical features

• measurement of several hepatitis B virus specific antigens and antibodies

• different serological markers or combination of markers are used to identify different HBV phases

• determines if they have acute, chronic or immune to it - due to vaccination or if they are susceptible

Hepatitis serology

• blood-borne transmission

• transmit 1-2 months before and after symptoms and people with acute or chronic infect with HBsAg present in the blood

• lowest carrier in USA, europe and Australia, middle carrier, china, africa, south america, highest carriers in aboriginal communties and central africa

• vaccine controlled disease

Hepatitis B epidemology

• recombinat DNA technology

• hard to grow in lab

• purified HBsAg protein aborbed into aluminium hydroxide and phosphate and small amount of yeast

• dose at birth and 3 doses after

• may be given by itself or with combination - infrarix hexa vaccine

Hepatitis B vaccination

• Flavivirdae, hepacivirus

• single stranded RNA

• enveloped

• different genotypes - genomic diversity - mutates easily

• antigenic drift - chronic infections

• a person can have multiple variants at a time

Hepatitis C

• mild

• limited to moderate elevation of liver enzymes

• hospitalisation - rare

• many cases progress to chronic liver disease some develop chronic active hepatitis and cirrhosis

• asymptomatic until late progression

• leads to hepatocellular carcinoma (HCC)

Hepatitis C clinical features

• blood borne contact - by needle sharing, haemophiliacs - blood clotting, haemodialysis patients

• routine screening in australia

• healthcare workers and sexual practises at high risk

• can be from mother to child but low risk

• small population of world is impacted, some people in australia are chronically infected

Hepatitis C

• no vaccine

• 6 major types with many subtypes

• geographical variation

• no good animal models to study

• limited culture

• hard to catch and prevent

• treatment - interferon alpha and anti-viral drugs

Hepatitis C treatment

• screening and testing blood, plasma, organ, tissue and semen donors and virus inactivation of plasma derived products

• counselling of persons with high risk drug or sexual practices

• infection control in health care workers and other high risk settings

• professional and public education

Hepatitis C prevention and control

• live in GI, some are pathogenic

• billions of people worldwide

• life cycle - trophozoite (feeding) cyst stages, (infective)

• transmission - faecal oral route

• Different life cycle stages, cysts more stable in environment

• pass into faeces already infective or soon to be

• Cyst appearance can be used to distinguish between pathogenic and non-pathogenic species.

Protozoa

• tropical and sub tropical countries

• trophozite - lives on mucosa of large intestine

• cyst pass out in faeces and is infective

• mild diarrhoea - small localised ulcers

• deep ulcerations of mucosa: blood and mucus in diarrhoea - amoebic dysentery

• treatment - Metronidazole/tinidazole act as antiamoebics that attack the trophozoite stage to eradicate the infection.

Entamoeba histolytica

• first intestine microbe seen in microscrope

• Traveller’s diarrhoea

• flagellate trophozoite, cyst - life cycle

• Trophozoite attach to mucosa of upper small intestine, large numbers can cover mucosa

• transmitted - contaminated drinking water, transmitted sexually

• Asymptomatic – self-limiting, 7-10 days, Chronic – can become serious, through inflammatory response - especially immunocompromised

• Treatment: metronidazole/ tinidazole,

Giardia intestinalis

• Cryptosporidium hominis

• complex life cycle - sexual and asexual phases in host

• oocysts shed in faeces, only after microbe sexual reproduction

• transmitted by contaminated water

• watery diarrhoea, moderate through to severe in immunocompetent individuals - may be chronic and life threatening

• diagnosis by faecal examination, concentration technique, special stain

• treatment for immuncompromised only

Cryptosporidium infections

• GI major portal of entry

• underdeveloped - enteric diseases - morbidity and mortality

• developed - mild and self limiting - severe in young and elderly and immunocompromised

General features of GI infections

• microbes are swallowed

• body defence are effective kill, remove and inactivate

• microbes rarely manage to survive in number to cause damage

• stomach acid, peristalsis

GI defences

• remain localised in the gut

• invade beyond gut and infect other sites

• transmission - pathogens need to be excreted in large numbers into environment to survive to infect new host

• contaminated food and water

GI infections

• gastroenteritis - nausea, vomiting, diarrhoea, abdominal discomfort

• diarrhoea - frequent or fluid stool - due small intestine effects - enterotoxin producing organisms 3 days

• dysentery - blood and pus in faeces, - pain, fever, abdominal cramps - invasive toxin producing organisms 7 days

• enteric fever - invasive organisms produce bacteraemia - systemic or fatal more than 1 week

• enterocolitis - inflammation of small and large intestine

descriptions of GI infection

• enterotoxin

Toxigenic

• enterotoxin damages epithelium

• or goes into blood. - bacteremia

Invasive

• gram negative rods

• part of normal flora

• produce exotoxins

• cell wall contains LPS - endotoxin - systemic infections - fever

Enterobacteriaceae

• used to used to identify different strains in a species through antibodies → serogroup

• for specific bacterial antigens

• distinguish between different strains within a species

• use for controlling epidemics

Serotyping

• Aerobic/facultative anaerobe

• Gram-negative, pleomorphic rod

• in large intestine

• indicator for faeceal contamination

• Coliforms– used to detect faecal contamination in food/water or products, not necessarily pathogenic

• Indicate that there may be other, pathogenic microbes

  present that are harder to detect

• classified according to O - cell wall, K capsule and H flagella antigens

• many use pili to attach to host

E.coli

• non pathogenic

• may be opportunistic

• virulence factors

• uti, primary pneumonia, neonatal meningitis, wound infections sepsis

• specific strains have specific symptom combination

• treated - antibiotic therapy and fluid replacement

E.coli infection

• Attaches with various adhesins and disrupts microvilli structure

• watery diarrhoea, fever, vomiting

• No exotoxin production

• irregular outbreaks in children and babies

Enteropathogenic E coli (EPEC)

• Plasmid-associated enterotoxin production

• profuse watery diarrhoea

• acute dehydration in infants

• traveller diarrhoea

• effects resource poor places

Enterotoxigenic E coli (ETEC)

• highly invasive - attach and enter by endocytosis

• Invade adjacent cells and destroys large intestine epithelium

• Ulceration results in diarrhoea with blood and mucus

• cause of diarrhoea in areas of poor hygiene

Enteroinvasive E coli (EIEC)

• Shiga toxin

• Food and unpasteurized milk - spread

• haemorrhagic colitis (bloody diarrhoea) and can cause haemolytic Uraemic Syndrome (rare) in children

• Toxin lyses RBC cause block kidney capillaries and causes kidney

  damage

Enterohaemorrhagic E coli (EHEC)

• Gram-negative bacillus

• classified into two species

• Salmonella enterica - warm blooded animals, including human

• Salmonella bongori– restricted to cold-blooded animals

• transmission between wild animals, humans, human food and sewerage

Salmonella

• many serotypes

• most do not cause disease but some are significant pathogens

• O (cell wall) and H (flagella) antigens

• don’t produce exotoxins

• cause systemic disease

Salmonella enterica

• Gastroenteritis– localised to the gut

• Bacteraemia - Acute gastroenteritis and spread to other sites - less common (only a few strains

• Enteric fever – bacteria spread and involve multiple organs - Can last for weeks if untreated

• Typhoid fever – more severe form of enteric fever - Caused by Salmonella typhi

Salmonella infections

• adhere to and induce host cells to internalize them

• Survive and multiply within endocytic vacuoles

• cross the epithelial layer and then into sub-epithelial tissue

• quite resistant to phagocytosis

• Diarrhoea - local inflammatory response causing fluid secretion

• nausea, vomiting, non-bloody diarrhoea, fever

• for typhimurium, enteritidis

Salmonella pathogenesis for gastroenteritis

• survive in macrophages and dendritic cells and infect the local lymphatic system then travel systemically

• Transported in infected cells to the liver, spleen, and bone marrow

• bacteraemia can occur

• Sustained fever - LPS

• Colonise gall bladder from liver

• Reinfect the GI tract - bile

Salmonella pathogenesis for enteric fever

• more severe form of enteric fever

• Salmonella enterica serovar Typhi (Salmonella typhi

• severe and may be lethal

• carrier and may persist in gall bladder

• shedding

Salmonella pathogenesis - typhoid fever

• Replacement of fluids and electrolytes

• antibiotics for fever but not for gastroenteritis

• Vivotif Oral - oral live attenuated typhoid vaccine

• Typherix or Typhim Vi – parenteral capsular polysaccharide vaccines, injected

• Vivaxim– combined capsular polysaccharide with Hepatitis A, injected

Salmonella treatment

• no H antigen - flagella

• Gram-negative rods

• Invasive and toxigenic infection - mucosal ulcerations

• Shigella sonnei– most common in developed countries,

  milder disease

• Shigella flexneri and Shigella boydii– most common in

  underdeveloped countries; causes more severe disease

• Shigella dysenteriae– most severe disease

Shigellosis

• stages - Initial non-invasive colonisation and toxin production - Watery diarrhoea due to enterotoxic activity of Shiga toxin

• Second stage invasion/damage of large intestine epithelium - Severity enhanced by cytotoxic activity of Shiga toxin

• dysentery with frequent small stools with blood and mucus, cramps, fever

Shigellosis

• neurotoxic, cytotoxic and enterotoxic

• enterotoxic - Binds to intestinal epithelial receptors and blocks absorption (uptake) of electrolytes, glucose, and amino acids

• Cytotoxic effect - inhibits protein synthesis causing cell death damage to microvasculature of the intestine leads to haemorrhage - blood and faecal leukocytes in stool

• Neurotoxic effect – Fever and abdominal cramping

Shigella toxin

• Vibrio cholerae

• Comma-shaped, motile, Gram-negative rod

• Salt tolerant (halotolerant) or halophilic

• fresh and salt water and seafood, free-living

• potent enterotoxin

• faecal-oral route - contaminated water and food, seafood

• 1-4 days incubation

• watery diarrhoea - rice water

• Dehydration, electrolyte imbalance, acidosis, circulatory collapse and possible eventual death

• most asymptomatic but carriers

• fluid replacement therapy but tetracycline can be used

Cholera

• different structures of O antigen

• V. cholerae - harmless

• subtype - o variation

• O1 and O139 cause disease

• vary in disease severity

Cholera identification

• colonises the intestine but does not invade

• strains produce a heat-labile exotoxin

• Enterotoxin (choleragin)

• 5 B sub-units target the toxin to the ciliated epithelial cell in the gut and causes the A subunit to enter cell

• In the cell the A sub-unit causes unregulated activation of adenylate cyclase and cAMP

• hypersecretion of chloride, bicarbonate and water from the cells, causing copious water diarrhoea and dehydration

Cholera pathogenesis

• not recommended

• Dukoral’ Oral Inactivated Vaccine - Contains: inactivated whole cell V. cholerae O1 in a mixture of serotype/biotype strains with recombinant protein cholera toxin B subunit

• not effective against the O139 strain

Cholera vaccine

• Campylobacter pylori

• normal colonises the stomach

• chronic, low level inflammation of gastric epithelia

• duodenal ulcers and gastric ulcers 

• able to survive acid ph and neutralise ph - non-pathogenic

Helicobacter pylori

• urease enzyme which helps neutralise pH and

• strains may be benefits

how Helicobacter pylori survives in the stomach

• Small, curved, s-shaped or spiral rods

• Gram-negative

• Motile, sometimes microaerophilic.

• c.jejuni and C. coli cause mild to severe diarrhoeal disease

• foodborne illness causing acute bacterial enteritis worldwide

• Poultry source

• commensal - live naturally inside the bodies of certain animals without causing them any harm, disease, or illness.

Campylobacter

• diarrhoea and also associated abdominal pain

• invasive bacteria which lead to colitis

• invade by endocytosis and produce a cytotoxin

• antibiotics

• rarely cause systemic dieases

Pathogenesis of Campylobacter

• Gram-positive rod

• diarrhoea and colitis after antibiotic therapy

• controlled by the normal flora of gut

• Antibiotics kill the normal flora and C. difficile is able to thrive causing it to toxins which damage epithelium

• hospital acquired infection

• Normal microbiota convert primary bile salts into secondary bile salts that then inhibit the growth of the vegetative form of C. difficile.

Clostridium difficile

• contaminate food and produce toxins

• S. aureus - Many strains produce an enterotoxin which is quite stable Cooking may kill bacteria but not inactivate toxin Acts on CNS to trigger severe vomiting (no diarrhoea)

• Botulism – Clostridium botulinum - environmental organism rare disease but toxin causes serious consequences as they block neurotransmission – paralysis of muscle due to inadequate cooking or food storage

Food poisioning