Lecture 3- gastrointestinal infections Flashcards
what is Campylobacter jejuni?
Common, around 50,000 cases/year
Associated with poultry and animal faeces
Gram –ve curved rod
Kampylos – curved in greek
Encodes flagella
Required for motility, biofilm formation and host colonisation
what is Listeria monocytogenes?
Found in sliced meats/cheeses/raw milk
Less common
approx. 80 cases a year in England/Wales
Very severe in high risk populations
Old, young, pregnant
Initially, fever, vomiting and diarrhoea
Can lead to systemic listeriosis, including meningitis, pneumonia, myocarditis
where does food poisoning come from?
Usually, from poorly cooked or contaminated food
Self limiting
Common causes (in UK)-
Campylobacter (most common), E. coli, Salmonella, Listeria
what is Viral gastroenteritis?
Acute watery diarrhoea, vomiting, fever
Spread from person-to-person
Frequently self limiting (expect in young children)
Rotaviruses (Reoviridae)
Vaccine introduced in 2008, decreases risk of death by 37–96%
Human caliciviruses – norovirus, sapovirus (Caliciviridae)
Norovirus mRNA vaccine phase 3 trial launched 2024
Astroviruses (Astroviridae)
No vaccine/treatment
Group F adenoviruses (Adenoviridae)
Live vaccine used by US army in 70-90s, no longer used
what is Cryptosporidium?
Apicomplexan parasite (related to malaria)
Causes watery diarrhoea
Usually self limiting
Significant cause of diarrheal-mortality in under 5s
Often associated with outbreaks
Recently linked to swimming pool in Perth
Infection through consumption of environmentally resistant oocysts
what is cholera?
John snow - Start of the science of public health/ epidemiology
1854 – Broad St pump
Once pump handle removed, cases declined
Disease of epidemics and pandemics
7th pandemic
Started in 1961 in Indonesia
Spread through Asia to Africa on the 1970s
To Peru in 1991
Thought to have been introduced there in the ballast water of a Chinese cargo ship or from crew suffering from cholera and somehow got into the water supply.
It managed to gain a foothold there because of an earlier decision by the health authorities to stop chlorination of the water supply because they thought chlorination, fluoridation etc. was bad for public health.
Caused 1m cases and 12000 deaths in South and Central America
what are the 3 major gastrointestinal infections?
cholera, shigella and salmonella
what are the clinical features of cholera?
Incubation 2-3 days, duration up to 7 days
Treatment:
Intravenous or oral fluid and electrolyte replacement with a simple glucose and salts solution
Profuse watery diarrhoea (rice-water stools) up to 24 L/day
40-60% mortality if untreated
<1% if treated
No inflammation in gut
what is the pathogenesis of cholera?
Large infective dose required
109-1011 organisms
Rapidly killed by gastric acidity
Colonisation of small intestine depends on
motility
production of mucinase (protease)
TCP (toxin-co-regulated pilus) adhesin
Symptoms caused by cholera toxin
Encoded by CTXΦ phage
Toxin binds to receptors on cells in the small intestine
Triggers increase in cAMP
Leads to active secretion
how do people become immune to cholera?
to both cholera toxin and bacterial surface antigens is necessary to prevent infection
Killed whole-cell vaccines given by injection are poorly effective
no longer recommended by WHO
New oral vaccines
Better for stimulating mucosal immunity, IgA antibodies
Three currently recommended:
Dukoral – inactivated monovalent
Shanchol, Euvichol-Plus – inactivated divalent
Two doses are 58–76% effective
what are the types of shigella?
Shigella - non-motile Gram-negative rods
(closely related to E. coli )
Shigella sonnei usually mild
Sh. flexneri, Sh. boydii more severe
Sh. dysenteriae most severe
what is the epidemiology of shigella?
human pathogens
no animal or environmental reservoir
person to person spread via contaminated water
Little asymptomatic spread
Shigellosis is primarily a disease of children and the elderly
Sh. dysenteriae (serotype 1)
Causes Dysentery
mainly associated with epidemics in developing countries
affects all ages
high fatality rate in children
Low infective dose:
10-100 organisms
survives stomach acidity
Easily spread where personal hygiene and sanitation are poor
nurseries, day-care centres, nursing homes, psychiatric hospitals, refugee camps
what are the clinical features of shigella?
Acute bloody diarrhoea
Incubation 1-4d, duration 5-7d
Diarrhoea with blood and mucus, abdominal cramps, fever
Dehydration may be severe
Frequent complication: kidney damage in S. dysenteriae infections (Shiga/Vero toxin)
Treatment
Oral rehydration therapy
Antibiotics only given in severe cases
Antibiotic resistance is common and plasmid-mediated
what is salmonella?
Motile, non-sporing Gram-negative rods
Facultative anaerobes
Two species:
enterica – infects mammals
bongori – infects reptiles
Salmonella enterica >2000 serotypes
S. enterica Typhi
human , systemic infection (typhoid fever)
no animal source
bloodstream and reticuloendothelial system infection
S. enteritidis, Typhimurium
Food poisoning salmonellae from animal source
fever, diarrhoea, vomiting, abdominal pain
what is S. Typhimurium?
Inflammatory response gives rise to disease symptoms
Patients may continue to excrete the organism for weeks/months after recovery
Watery or bloody diarrhoea
Usually self limiting (mortality <1%)
Treatment to restore lost fluids
what is typhoid and enteric fever?
Mary Mallon (1869 -1938), known as Typhoid Mary - first person in the US identified as an asymptomatic carrier of the pathogen associated with typhoid fever (Salmonella typhi)
An invasive disease restricted to humans
Associated with lack of public health services/contaminated food/water
Caused by
Salmonella Typhi
Salmonella Paratyphi A, B, C
Symptoms:
Fever, abdominal pain, headaches, weakness, confusion, mild diarrhoea and vomiting, skin rash (rose spots)
Lasts for weeks-months (untreated)
Systemic growth of bacteria in intestine, gall bladder, bone marrow and blood
Mortality rate 10-30% if untreated
Treatment : Antibiotics, fluids
Expresses Vi antigen
-Prevents phagocytosis by immune cells
what is the role of the normal flora in resistance to infection?
Oral infection of mice with Salmonella typhimurium
Oral LD50 (dose that kills 50% of animals infected)
conventional mice: 1 x 106 bacteria (CFU)
germ free mice: 3 - 5 CFU
No difference in LD50 if S.typhimurium given to mice by injection to bypass the gut (I/V or I/P)
how are pathogens spread?
Some of these pathogens may be transmitted by food and other means e.g. Salmonella sp. including S.typhi , and polio virus, whereas V. cholerae is transmitted mainly via water. However, the water route is very important e.g. typhoid fever has been virtually eliminated in many parts of the world as a result of effective water treatment methods. Also, when there is a breakdown in the supply of clean water due to natural disasters such as floods and earthquakes or in wars, and the water becomes contaminated, epidemics e.g. of, cholera, dysentery, typhoid often follow.
what is the microbiome?
Highly diverse communities of bacteria that live in the gut
300-1000 species/person
Very variable between people,
Generally, an individual’s population is fairly stable after age of 2
what are the zoonotic salmonella sources? and what is the pathogenesis?
Live in food animals GI tract (Salmonella food poisoning serotypes)
In man, large numbers (105-6) for infective dose
usually only localized gastroenteritis, not systemic infection
S. Enteritidis PT4 - vertical transmission in poultry
from infected adult -> egg -> chick ->infected adult
Cross-contamination - spread from raw meat and poultry to cooked food
Inadequate cooking and storage at a temp suitable for growth
Toxins not clearly demonstrated
Localised invasion of intestinal mucosa - facultative intracellular parasites
Type III secretion systems essential for virulence
Bacteria pass through M cells, taken up by macrophages, multiply and lyse macrophages
what barriers must be overcome to cause disease?
Antibiotics
kill normal flora
Diet
E.g. high iron diet can support pathogen growth
Pathogen adaptations
Adherence
Survival in acid stress
Toxin production
how do diseases spread from cell to cell?
Spreads between cells on actin comets
Like Vc, they are human (and some primates) pathogens, no animal reservoir, but not generally found in environment and so person to person spread is most important, although water is also important. Asymptomatic carriers occur but not as often as in cholera
Shigellosis is primarily a disease of children and the elderly
Sf and Ss are the most common species in developed countries.
Sh. dysenteriae (serotype 1) is mainly associated with epidemics in developing countries, affects all ages but has a high fatality rate in children.
