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Salmonella Infections in Humans

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rod-shaped, non-spore-forming Gram-negative bacterium. belongs to the family ... Motile by peritrichous ... are chickens, turkeys, pigs, and cows ... – PowerPoint PPT presentation

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Title: Salmonella Infections in Humans


1
Salmonella Infections in Humans
  • Mark Pallen

2
Salmonella infections in humans
  • Enteric fever
  • typhoid and paratyphoid fevers
  • typhi, paratyphi A, B, C
  • systemic infection
  • infects only humans
  • GI symptoms may not be evident
  • Salmonella gastroenteritis
  • non-typhi serovars
  • zoonosis predominantly food-borne
  • can be complicated by septicaemia
  • more common with some serovars, e.g. S. dublin
    (15 mortality rate when septicemic in the
    elderly)
  • Metastatic disease, e.g. osteomyelitis

3
Overview
  • Bacteriology
  • Epidemiology
  • Clinical features
  • Diagnosis
  • Treatment
  • Prevention
  • Pathogenesis

4
Bacteriology
  • Salmonella enterica
  • one species, 2000 serovars
  • Non standard nomenclature common
  • S. enterica serovar Typhimurium
  • or S. typhimurium
  • rod-shaped, non-spore-forming Gram-negative
    bacterium
  • belongs to the family Enterobacteriaceae
  • close relative of E. coli
  • Motile by peritrichous flagella (H antigen).
  • nonmotile exceptions S. gallinarum and S.
    pullorum

5
Antigenic Structure
  • Kauffmann-White antigenic scheme
  • agglutination reactions with specific antisera
    against Salmonella antigens
  • O antigens
  • characteristic sequence of repeating
    polysaccharide units in LPS.
  • H antigens
  • flagellar antigens (protein) and may occur in one
    of two phase variations.
  • Vi antigen
  • a capsular polysaccharide homopolymer of N-acetyl
    galactosamineuronic acid

6
Epidemiology Enteric fever
  • person-to-person spread
  • no animal reservoir
  • contamination with human faeces
  • usual vehicle contaminated water.
  • occasionally, contaminated food (usually handled
    by an individual who harbours S. typhi)

7
Epidemiology Non-typhoidal serovars
  • zoonosis with enormous animal reservoir
  • common animal reservoirs are chickens, turkeys,
    pigs, and cows
  • contaminated food is major vehicle, usually
  • red and white meats, raw eggs, milk dairy
    products
  • many other possibilities, from spices or
    chocolate to cannabis
  • can follow direct contact with infected animals
    (e.g. farm trip, reptiles as pets)

8
Epidemiology Non-typhoidal serovars
  • outbreaks common
  • In Catering establishments
  • In Hospitals
  • Stanley Royd Hospital outbreak
  • now careful attention to hospital kitchen hygiene

9
Epidemiology Non-typhoidal serovars
  • Food-borne transmission by
  • contamination of cooked food by raw food
  • failing to achieve adequate cooking temperatures.
  • secondary cases by person to person spread are
    common in outbreaks
  • food handlers who practice good hygiene very
    rarely responsible for outbreaks

10
Salmonella in eggs
  • various Salmonella serovars isolated from the
    outside of egg shells
  • S. enteritidis PT4 present inside the egg, in the
    yolk
  • vertical transmission
  • deposition of the organism in the yolk by an
    infected layer hen prior to shell deposition.

11
Infectious dose
  • typically about 1,000,000 bacteria
  • much lower if the stomach pH is raised
  • much lower if the vehicle for infection is
    chocolate
  • protects the bacteria in their passage through
    the stomach
  • an infectious dose of about 100 bacteria

12
Epidemiology carrier states
  • carrier state may last from many weeks to years
    with faecal shedding
  • convalescent carrier
  • chronic carrier
  • 3 of persons infected with S. typhi
  • 0.1 of those infected with non-typhoidal
    salmonellae
  • potential for cross-contamination of foods by the
    infected handler
  • Typhoid Mary Mallone
  • but more common in textbooks than in real life

13
Laboratory Diagnosis
  • Isolated from stool, blood and urine in enteric
    fever (blood cultures need to be taken!)
  • Isolated from stool in gastroenteritis
  • Appears as a non-lactose fermenter
  • on MacConkey agar or similar selective agar

14
Laboratory Diagnosis
  • Biochemical tests and serological tests must be
    done in parallel
  • Some other bacteria, e.g. Citrobacter, may have
    similar serological profiles
  • Commercial kits commonly used, e.g. API20
  • Phage typing done for epidemiological purposes
  • E.g. to find source of outbreak
  • Certain phage types predominate nationally
  • S. typhimurium PT4
  • S. enteritidis DT109

15
Treatment
  • Gastroenteritis
  • replace fluid loss by oral and intravenous routes
  • antibiotics are not recommended for uncomplicated
    gastroenteritis
  • do not shorten illness
  • prolong excretion.
  • antibiotic therapy reserved for the septicaemic
    and metastatic disease
  • Typhoid fever and enteric fevers should be
    treated with antibiotics
  • usually ciprofloxacin
  • rise of resistance

16
Prevention
  • Remove source
  • Salmonella free life-stock
  • Vaccinate chicks
  • Interrupt transmission
  • Good food hygiene
  • Cook food properly
  • Keep raw and cooked foods apart
  • Public Health clean water
  • Strengthen host
  • vaccination

17
Salmonella vaccines
  • Vaccination of travellers against typhoid
    recommended, but does not remove need for good
    hygiene
  • Three licensed vaccines
  • Traditional heat-killed
  • very reactogenic
  • Vi subunit vaccine
  • live oral vaccine, S. typhi Ty21A
  • Salmonellas can act as live attenuated carriers
    for other antigens
  • So far only experimental
  • No vaccines for gastroenteritis

18
Clinical Features Enteric Fever
  • incubation period 10 to 14 days
  • septicaemic illness
  • myalgia and headache
  • fever
  • splenomegaly
  • leukopenia
  • abdominal pain
  • Rose spots (macular rash on abdomen)
  • 10 fatal
  • positive blood, urine, and stool cultures
  • Sequelae intestinal haemorrhage and perforation

19
Clinical features Gastroenteritis
  • incubation period depends on dose
  • symptoms usually begin within 6 to 48 hours
  • Nausea and Vomiting
  • Diarrhoea
  • Abdominal pain
  • Myalgia and headache
  • Fever
  • duration varies, usually 2 to 7 days
  • seldom fatal, except in elderly or
    immunocompromised

20
Pathogenesis Gastroenteritis
  • Pathogenic salmonellae ingested in food survive
    passage through the gastric acid barrier
  • invade intestinal mucosa
  • invasion of epithelial cells stimulates the
    release of proinflammatory cytokines
  • induces an inflammatory reaction
  • causes diarrhoea and may lead to ulceration and
    destruction of the mucosa

21
Pathogenesis Enteric Fever
  • Bacteria invade mucosa or Peyer's patches of
    small intestine (?M cells), pass into mesenteric
    lymph nodes where they multiply and then enter
    the blood stream via the thoracic duct
  • Primary bacteraemia cleared by RES, bacteria
    multiply in RES cells and destroy them
  • Facultative intracellular parasites

22
Pathogenesis Enteric fever
  • Secondary bacteraemia occurs and results in
    spread to other organs.
  • Infection of the biliary tract.
  • Multiplication in biliary tract leads to seeding
    the intestine with large numbers of bacteria.
  • Involvement of intestinal lymphoid tissue may
    lead to necrosis and ulceration.
  • In untreated nonfatal cases, temperature drops in
    3 to 4 weeks (onset on immunity?)

23
S. typhimurium in the mouse
  • S. typhimurium
  • causes gastroenteritis in humans
  • causes typhoid-like disease in mice
  • infection can be established orally or
    systemically
  • used as model of typhoid
  • primary mechanisms of pathogenesis
  • invasion of the intestine
  • survival and growth in macrophages

24
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25
Invasion
  • membrane ruffling
  • depends on Spi1 Type III secretion system
  • Spi1 effectors
  • SopE affects actin cytoskeleton
  • SipA binds to actin, inhibits depolymerization
  • SopB inositol phosphate phosphatase
  • SptP PTPase, disrupts the actin cytoskeleton

26
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27
Invasion
  • Salmonella enters host cells by inducing host
    cell membrane ruffling
  • membrane ruffles non-specifically wrap around the
    bacteria and pull them into the cell
  • Salmonella end up in membrane-bound vesicles
    called Salmonella-containing vacuoles (SCV). 
  • SCVs are unique environments within the cell
    defined by the bacteria within them
  • As they mature, SCVs do not follow the defined
    routes of cellular trafficking of vesicles and
    differ in their composition from normal phagosomes

28
Survival in cells
  • Spi2 Type III secretion system
  • expressed in cells
  • activated by acidic pH in phagosome
  • mutants severely attenuated in mice
  • currently under intense investigation
  • PhoP/PhoQ
  • Pags
  • Prgs

29
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30
Salmonella can also trigger apoptosis through Spi1
31
Salmonella cellular subversion
32
Salmonella cellular subversion
From Nature 412, 701
33
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34
Salmonella-induced filaments labelled with
antibodies against lysosomal glycoprotein
35
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36
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37
http//www.hhmi.org/lectures/1999/index.htm
38
Salmonella Genome Sequencing Projects
  • Completed
  • S. typhiumurium LT2 at WashU
  • Multi-resistant S. typhi from Vietnam at Sanger
    Centre
  • Ongoing
  • Salmonella five-pack at Sanger

39
Online bibliography
  • http//www.hhmi.org/lectures/1999/index.htm
  • http//www.sanger.ac.uk/Projects/
  • http//genome.wustl.edu/gsc/bacterial/salmonella.s
    html
  • http//www.salmonella.org/
  • http//www.who.int/inf-fs/en/fact149.html
  • http//www.bmj.com/cgi/content/full/313/7065/1094
  • http//vm.cfsan.fda.gov/mow/chap1.html
  • http//129.109.112.248/microbook/ch021.htm
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