Salmonella

Background:

• Over 2000 antigenic types
• Salmonella enterica subspecies enterica serotype Enteritidis = S. Enteritidis.
• They can cause a mild self limiting GI illness ranging to life threatening systemic disease.
• Relative fall in incidence in the UK, although this is still the highest cause of community-associated diahorrea in the developing world.
• Characteristics:
  • Facultatively anaerobic
  • Gm(-) bacilli
  • Grow on a wide range of simple media
  • Highly motile
• Antigens:
  • 'O' antigen: somatic heat stable LPS, anchored on the outer membrane. There is genetic conservation of the lipid A/LPS core region. These are usually just numbers.
  • 'H' antigen: these are the flagellar protein subunits, and in some microbes two distinct flagellar structures are expressed (Phase I & Phase II genes). These are lower case letters (Phase I) & lower case letters with numbers (Phase II).
  • 'V_i' antigen: the virulence factor is expressed in certain serotypes. This protein may encompass the whole bacterium, making detection of 'O' antigens difficult.
  • Designantion by Kauffmann-White: ['O' Ag] [Phase I 'H'] [Phase II 'H'], e.g. S. Typhi (9, 12, [Vi]: d-). Here only one flagellar phase is expressed.
  • Differentiation by phage typing and AB_x sensitivity (e.g. S. Typhimurium is very resistant).

Pathogenicity:

• Infects all vertebrates
• Wide range of clinical syndromes
• S. Typhi & S. Paratyphi are essentially human pathogens
• Incubation period = 10-14 days, followed by enteric fever (septicaemic illness).
• Some Salmonellae infect animals
• S. Typhimurium Type 104 = bovine zoonosis
• Infections in the developing world occur from a relatively small number of serotypes.
• Ingested innoculum → colonisation of gut → overgrowth and owerpowering of host defences → infection
• Infective dose: 10⁶ - 10⁹ for S. Typhi (10³ suggested for some outbreaks).
• Virulence factors:
  • vary amongst strains & serotypes
  • depends on the vehicle in ingestion (bacteria can be protected from stomach acid if hiding in food particles)
  • Relative increased incidence in <1 yr olds may be due to more aggressive I_x.
  • Characteristics:
    • ability to tolerate bile
    • S. Typhimurium (ST) expresses Type 1 fimbriae → adhere to α-mannose containing molecules on the surface of ileal microvilli
    • S. Enteriditis (SE) express three types of fimbriae (e.g. SEF 14), the expression of which appear to be influenced by environmental conditions
    • SE & ST also have non-fimbrial adherence molecules; multiple types expressed in pathogenicity islands (n. DNA sequences that encode several pathogenic mechanisms):
      • Bacterial adhesins
      • Adhesin receptors translocated into the host intestine (i.e. they insert their own binding sites into the cells of the gut epithelium)
  • Bacterial adhesion leads to degeneration of microvilli and entry into the intestinal epithelia.

Clinical Syndromes: 1) Enteric Fever:

• S. Typhi or S. Paratyphi A, B or C
• More severe for S. Typhi
• Penetration of the ileal mucosa allows access to the mesenteric nodes via the lymphatics. After multiplication they drain into the SVC via the thoracic duct.
• 1^o bacteraemic phase in the first 7-10 days of the incubation period allows infection of the liver, kidneys & bone marrow.
• Multiplication in these organs allows a second phase of heavy bacteraemia leading to fever and clinical illness.
• From the GB, further invasion of the Peyer's patches leads to gut mucosal infiltration, necrosis and typhoid ulcers.

• Incubation time can vary from 3 - 50 days (usually 14 days)
• Insidious onset: dry cough, dull headache, tender abdomen. Diahorrea uncommon early, and patients mybe constipated.
• Step-wise increase in fever, remains high for 7-10 days.
• Relative bradycardia despite fever, hepato-splenomegaly, rose spots (REM no scar):

• Relapse occurs in 5-10% of untreated cases, with 2^o illness being mild.
• Severe intestinal haemorrhage & rupture can occur at any time of the disease.
• Classic typhoid had a mortality of 20%.
• Chronic bacteraemia may occur in endemic areas where schistomiasis co-exsists.
• Some serotypes present as diahorrea.

2) Gastro-enteritis & Food Poisoning:

• Diahorrea, nausea, headache, malaise. Vomiting is rare.
• 8-48 hr incubation.
• Abrupt onset, short course, self-limiting.
• 2-3 loose stools → loads of green watery stools, prostration, hypotension, dehydration, ARF.
• Severe infection at the extremes of age and those who are immunocompromised.

3) Bacteraemia & Metastatic Disease:

• Transient bacteraemia occurs in up to 4% of cases of acute gastroenteritis.
• Localized foci (abscesses)may occur in tissues (salmonellae can survive in macrophages) with pre-exsisting damage:
  • Atherosclerotic plaques
  • Joint prostheses
  • Other implants
  • Bony disease (e.g. osteomyelitis & sickle cell disease)
  • Suppurative osteomyelitis may occur as part of 2o or 1o infection.
• May cause meningitis in neonates and children.
• Long term survival in the liver, billiary tree, kidneys & bone marrow results in a carrier state.

4) Prolonged carrier state:

• Organism excreted in the stool for days or weeks after resolution of clinical disease. This ususally leads to complete clearance.
• Chronic carriers excrete salmonella for a year or more - up to 5% of convalscents from typhoid/paratyphoid. GNBs present in the billiary tree and to a lesser extent the urine.
  • <1% <20yrs become carriers
  • >10% >50yrs.
  • Female:male = 2:1.

Laboratory Diagnosis:

• Desoxycholate-citrate agar or xylose-lysine desoxycholate agar (XLD) can be used to isolate salmonellae from stool.
• Tetrathionate or selenite broth can be used to detect small amounts from environmental samples.
• Suspicious colonies: check with O & H antigens, biochemical API testing.
• Negative report after 48 hrs in enrichment cultures.
• Enteric Fever:
  • Salmonellae are recovered from the blood in the first 7-10 days and during relapses.
  • Can be recovered from clotted blood samples too → digest clot with strep then incubate in broth.
  • Stool & urine culture: positive results here may mean the patient is a carrier.
    • Typhoid fever: stool +ve from week 2, urine +ve from week 3.
  • Paratyphoid B: much shorter clinical course: earlier diarrhoea, stool cultures positive in 1^st week.
• Serology:
  • ELISA
  • IgG difficult to interpret if past infection
  • Further confusion with cross reaction of Igs
• Food poisoning:
  • Enteriditis/Typhimurium ID'd by: phage typing, AB_x resistance, PFGE & plasmid.

Treatment:

• Here
• Remember Typhoid Mary.
• Chronical asymptomatic carriers:
  • If billiary disease: cholecystectomy AND AB_x (amoxicillin, ampicillin, septrin, cipro - prolonged courses).
  • Adequate sanitat.ion.
  • Hand hygiene
• Vaccination:
  • Heat-killed phenol-preserved whole-cell vaccines contain a mixture of cultures of Typhi, Paratyphi A & B (TAB) has been used in endemic countries.
  • Now capsular (V_i) polysaccharide or oral live-attenuated vaccines are used.
  • Recommended for travellers to Eastern Europe.
• Salmonella Food Poisoning:
  • May occur when septicaemic animals are slaughtered.
  • Abattoir cross-contamination.
  • Poultry - all of our UK eggs are safe (!)
  • Cook food well.
  • Beware of foods containing raw eggs.
  • For prevention all the usual stuff.

AMH.