Salmonella Infections in Humans

Mark Pallen

Salmonella infections in humans
• Enteric fever
– – – – – typhoid and paratyphoid fevers S. 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

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

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

• Vi antigen – a capsular polysaccharide homopolymer of N-acetyl galactosamineuronic acid .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.

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

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

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

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

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. .

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 .000.Infectious dose • typically about 1.

typhi – ~0.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.1% of those infected with nontyphoidal salmonellae • potential for cross-contamination of foods by the infected handler – “Typhoid Mary” Mallone – but more common in textbooks than in real life .

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. and stool cultures • Sequelae: intestinal haemorrhage and perforation . urine.

usually 2 to 7 days • seldom fatal.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. except in elderly or immunocompromised .

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 .

bacteria multiply in RES cells and destroy them • Facultative intracellular parasites .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.

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

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 .

inhibits depolymerization – SopB inositol phosphate phosphatase. disrupts the actin cytoskeleton • Invasome – Bacterial surface appendage expressed when in contact with host cells . – SptP: PTPase.Invasion • membrane ruffling • depends on Spi1 Type III secretion system • effectors of invasion – SopE affects actin cytoskeleton – SipA binds to actin.

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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 • Induction of apoptosis – Spi1-dependent – SipB-mediated .

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 .

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

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

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 .

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 .Salmonella vaccines • Vaccination of travellers against typhoid recommended.

Salmonella Genome Sequencing Projects • S. typhiumurium LT2 at WashU • Multi-resistant S. typhi from Vietnam at Sanger Centre • Will allow delineation of how Salmonella became a pathogen .

cfsan.sanger.html http://www.fda.org/ http://www.ac.109.gov/~mow/chap1.112.uk/Projects/S_typhi/ http://genome.com/cgi/content/full/313/7065/1094 http://vm.wustl.edu/gsc/bacterial/salmonella.shtml http://www.salmonella.248/microbook/ch021.Online bibliography • • • • • • http://www.htm .who.html • http://129.int/inf-fs/en/fact149.bmj.

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