Transcript Slide 1

Salmonella Infections
Hossam Al-Tatari, MD
What are we going to talk about ?
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Microbiology
Epidemiology
Pathogenesis
Salmonellosis Syndromes
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Diagnostic Tests
Treatment and control measures
Vaccines
Some more interesting stuff in between
– Extra emphasis on Typhoid fever
Microbiology
• Gram-negative flagellated, facultatively
anaerobic bacilli
• Enterobacteriaceae family
• Most serotypes that cause human disease are in
sero- groups A through E
• Salmonella typhi is classified in serogroup D
Microbiology
• It has three major antigens:
– H or flagellar antigen
– O or somatic antigen
– Vi antigen (possessed by only a few types: namely
Typhi, Paratyphi C and Dublin )
• The cell envelope contains a complex
lipopolysaccharide (LPS) structure which may
function as an endotoxin
Microbiology
• The most frequently reported human isolates in
US:
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typhimurium (serogroup B)
heidelberg (B)
enteritidis (D)
newport (C2)
infantis (C1)
agona (B)
thompson (C1)
montevideo (C1)
Epidemiology
• The principal reservoirs for nontyphoidal
Salmonella organisms are animals,
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Poultry
Livestock
Reptiles
Pets
• S. typhi is found only in humans.
Epidemiology
• The major vehicles of transmission are foods of
animal origin,
– Poultry products and red meat
– Eggs: Unlike egg borne salmonellosis of past
decades, the current epidemic is due to intact and
disinfected grade A eggs
– Unpasteurized milk
Epidemiology
• Other modes of transmission:
– Foods, such as fruits, vegetables, alfalfa sprouts,
and rice
– Contaminated water
– Contact with infected reptiles (eg, pet turtles,
iguanas, and others)
– Contact with contaminated medications, dyes, and
medical instruments
Epidemiology- S.Non-typhi
• In US
– 1.4 million human infections due to S. non-typhi
– 16,000 hospitalizations
– 580 deaths
• 1972—2000: 58 raw milk--associated outbreaks
were reported to CDC
SALMONELLOSIS
Reported cases per 100,000 population, by year,
United States, 1972-2002
TYPHOID FEVER
Reported cases, by year,
United States, 1972-2002
Epidemiology- S. Non-typhi
• Most reported cases are sporadic
• Outbreaks in and outside institutions exist
throughout the world
• Multistate outbreak of Salmonella
Typhimurium infections associated with
drinking unpaseurized milk. Illinois, Indiana,
Ohio, and Tennessee, 2002-2003.
MMWR Vol 52, No 26;613 07/04/2003
Epidemiology- S. typhi
• Approximately 400 cases per year of typhoid
fever are reported in US.
• Cases of S. typhi in US usually are acquired
during foreign travel.
• Typhoid infects 16 million people worldwide
each year and kills 600,000.
Endemic Areas
The Big News in 2001
Salmonella bacteria
sequenced
Bugs behind typhoid and food poisoning
give up genetic secrets.
Nature, 25 October 2001
• Genomes of two strains (typhi and typhimurium) have
been sequenced
• The genome data should improve diagnostic tools
• "If we could block S. typhi transmission in humans, we
could eradicate it altogether - it's got nowhere else to
go," says Julian Parkhill the leader of the Typhi genome
project
• Typhimurium's sequence reveals 50 previously unknown
genes that code for proteins on its surface. These are
potential vaccine or drug targets
Back to Epidemiology
• Attack rates. Two peaks:
– Persons younger than 5 years mainly during the first
year of life
– Older than 70 years
• Highest morbidity and mortality:
– Infants
– Elderly persons
– Persons with an underlying disease:
hemoglobinopathies, malignant neoplasm, AIDS, and
other immunosuppressive conditions
Back to Epidemiology
• Organism excretion:
– 45% of those < 5 years of age continue to excrete it
by 12 wk post infection
– 5% of older children and adults continue to excrete
it by 12 wk post infection
– Antimicrobial therapy can prolong excretion.
– Approximately 1% continue to excrete it for > 1 year
Back to Epidemiology
• The incubation period
– For gastroenteritis is 3 hours to 3 days
– For enteric fever, the incubation period is 3
days to 3 moths but typically is 1 to 2 weeks
Pathogenesis
• In healthy human volunteers, a median dose of
at least 10,000 organisms was necessary to
produce symptoms
• Patients with low stomach acidity (e.g.: on
proton pump inhibitor) may have disease with
smaller inoculums
• It produces two types of toxins:
– Enterotoxins: Heat Labile enterotoxin
– Verotoxins or Shiga-like toxins
Pathogenesis
• Invades the epithelium multiply
intracellularly  spread to mesenteric lymph
nodes  the systemic circulation they are
taken up by the reticuloendothelial cells
organism confined and controlled.
• Depending on the serotype and the
effectiveness of the host defenses against
that serotype, some organisms may infect the
liver, spleen, gallbladder, bones, meninges, and
other organs
Salmonellosis Syndromes
• Any serotype can produce any of the syndromes
• Enteric fever S. typhi, S. paratyphi-A, and S.
schottmuelleri
• Septicemia or focal infections S. choleraesuis
• GastroenteritisS. typhimurium and S.
enteritidis
Typhoid Fever, History
• Often asymptomatic during incubation period,
except for diarrhea in 10-20%.
• As bacteremia develops, fever begins, which
typically increases in a step-wise fashion over
2-3 days.
• Most have headaches, malaise, constipation and
mild nonproductive cough.
Typhoid Fever, Physical
• 1st week:
– Temperature start rising
– Vague symptoms of fatigue and malaise
– Diarrhea or constepation
Typhoid Fever, Physical
• Rose spots:
– Crops of 2-4 mm diameter pink papules on the upper
abdomen and lower chest. Appear in clusters of 5-15.
– Between the seventh and twelfth days.
– Caused by bacterial embolization
– Culture of skin snips of the spots is usually positive.
– Relative bradycardia and a dicrotic pulse are also
common at this time.
Typhoid Fever, Physical
• 2nd week:
– toxic, apathetic with sustained pyrexia.
– Abdominal distension starts
– hepatosplenomegaly is common
Typhoid Fever, Physical
• 3rd week
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toxicity increases and pyrexia persists
delirious state (typhoid state) emerges.
Pronounced abdominal distension develops
liquid, foul, green-yellow diarrhea (pea soup
diarrhea) is common.
– Death may occur at this stage from overwhelming
toxemia, myocarditis, intestinal hemorrhage, or
perforation.
Typhoid Fever, Physical
• 4th week
– fever, mental state, and abdominal distension slowly
improve
– intestinal complications may still occur
– most relapses occur at this stage
Typhoid Fever,
Ocular Manifestations
• rare and occur in association with systemic
illness
• lid abscesses
• corneal ulcers
• uveitis
• vitreous hemorrhage
• retinal hemorrhage or detachment
• optic neuritis
• extraocular muscle palsies
• orbital thromboses and abscesses
Typhoid Fever, Diagnostic Tests
• Most patients have one or more of the
followings
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anemia, thrombocytopenia, and relative lymphopenia
elevated erythrocyte sedimentation rate
slightly elevated PT & PTT,
decreased fibrinogen levels
ALT/AST and serum bilirubin elevated to twice the
reference range
– mild hyponatremia and hypokalemia.
Typhoid Fever, Diagnostic Tests
• Definitive diagnosis requires isolation of the organism
• Most sensitive method of isolating S typhi is obtaining
a bone marrow aspirate (BMA) culture.
• S typhi can be isolated from BMA even if patients have
been taking antibiotics for several days.
• Blood and stool culture are usually positive in 85-90%
during the first week, declining to 20-30% thereafter.
Typhoid Fever, Diagnostic Tests
• Cultures from skin snips of rose spots is positive in
65%.
• A single rectal swab culture at hospital admission is
positive in 30-40%
• S typhi has been isolated from the cerebrospinal fluid,
peritoneal fluid, mesenteric lymph nodes, resected
intestine, pharynx, tonsils, abscess, bone, and urine,
among others.
Typhoid Fever, Diagnostic Tests
• The Widal test measures agglutinating antibodies
against flagellar (H) and somatic (O) antigens of S
typhi.
• In acute infection, O antibody appears first, rising
progressively, later falling, and often disappearing
within a few months.
• H antibody appears slightly later but persists longer.
• Sensitivity, specificity, and predictive values of this
test vary dramatically among laboratories
Typhoid Fever, Diagnostic Tests
• Several other serology tests are available. But
non proved to be clinically helpful.
• PCR:
– A new PCR detected 11 of 12 culture-confirmed and
4 culture-negative clinically suggestive typhoid cases
– Not commercially available yet.
Treatment
Treatment
• Antimicrobials are needed in severe diseases (such as
typhoid, non–S typhi bacteremia, or osteomyelitis)
• Indications for antimicrobial therapy of salmonella
gastroenteritis:
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Infants younger than 3 months of age
malignant neoplasms
hemoglobinopathies
HIV infection or other immunosuppressive illnesses or
therapy
– chronic gastrointestinal tract disease
– severe colitis
Treatment
• Ampicillin, amoxicillin, trimethoprimsulfamethoxazole (TMP-SMX), cefotaxime,
ceftriaxone or fluorquinolones
• Strains acquired in developing countries often
exhibit resistance to many antimicrobial agents
but usually are susceptible to ceftriaxone or
cefotaxime and to fluoroquinolones (eg,
ciprofloxacin or ofloxacin)
Treatment
• Domestically acquired S typhimurium infections
are increasingly drug-resistant
• Approximately one third of all S typhimurium
isolates are resistant to ampicillin,
chloramphenicol, streptomycin, sulfonamides,
and tetracycline
Treatment
• Length of treatment
– 7- to 10-day course of ceftriaxone
– 5- to 7-day course of ofloxacin or ciprofloxacin.
– For Salmonella meningitis, ceftriaxone or
cefotaxime is recommended, often for 4 weeks or
longer
– 4 to 6 weeks of therapy to prevent relapse
• localized infection (such as osteomyelitis or abscess)
• HIV patients with bacteremia
Treatment…Be careful….!!!
• Relapse is common after completion of therapy;
retreatment is indicated
• Strain susceptibility should be interpreted with
caution; clinical failure has been reported in
patients with typhoid fever treated with
cephalexin, aminoglycosides, and secondgeneration cephalosporins despite in vitro
susceptibility
Treatment
• How should we treat chronic carriers (>1y)
– In children: high-dose IV ampicillin or high-dose PO
amoxicillin combined with probenecid or
cholecystectomy.
– In adults: Ciprofloxacin is the drug of choice
• What is the rule of steroids in severe disease
– may be beneficial to patients with severe enteric
fever, which is characterized by delirium, obtundation,
stupor, coma, or shock.
– The usual regimen is high-dose dexamethasone given
intravenously at an initial dose of 3 mg/kg, followed by
1 mg/kg every 6 hours for a total course of 48 hours
Treatment
• What about pro-biotics?
– Flora Balance contains bacillus laterosporus BOD
which was discovered in Iceland in the 1980's
– Although there have been sporadic reports of
success with these agents, these products have not
been evaluated by the FDA
Control Measures
• Do these patients need isolation?
– Standard precautions
– Contact precautions should be used for diapered and
incontinent children for the duration of illness
– In children with typhoid fever, precautions should
be continued until cultures of 3 consecutive stool
specimens obtained at least 48 hours after
cessation of antimicrobial therapy are negative for
S typhi
Control Measures
• Proper sanitation methods for food processing and
preparation
• Sanitary water supplies
• Proper hand washing
• Sanitary sewage disposal
• Exclusion of infected persons from handling food
• Prohibiting the sale of reptiles for pets
• Reporting cases to appropriate health authorities, and
investigating outbreaks
• Eggs and other foods of animal origin should be cooked
thoroughly
• Raw eggs and food containing raw eggs should not be
eaten
Control Measures
• Are there any special instructions for Day care
centers?
– When S typhi disease is identified in a symptomatic
child care attendee or staff member, stool
specimens from other attendees and staff members
should be cultured, and all infected persons should
be excluded until 3 consecutive stool cultures are
negative for S typhi
– This doesn’t apply to non-typhi salmonella
– Antimicrobial therapy is not recommended for
persons with asymptomatic infection or
uncomplicated diarrhea or who have been exposed to
an infected person.
Typhoid Vaccine, Indications
• Travelers to areas where a risk of exposure to
S typhi is recognized.
• Persons with intimate exposure to a
documented typhoid fever carrier
• Laboratory workers with frequent contact with
S typhi
• Persons living in typhoid-endemic areas outside
the United States
Typhoid Vaccine
• The degree of protection is limited and can be
overcome by ingestion of a large bacterial inoculum
• Two typhoid vaccines are available for civilian use
in USA. An older one is still available in third world
countries
• A fourth is available only to the military
• The demonstrated efficacy of the 3 licensed
vaccines ranges from 17% to 66%
• Selection of vaccine is based on the age of the
child, and possible contraindications and reactions
Typhoid Vaccine,
Oral Ty21a vaccine
• Children (6 years of age and older) and adults should
take 1 enteric-coated capsule every 2 days for a total
of 4 capsules
• Each capsule should be taken with cool liquid, no
warmer than 37°C (98°F), approximately 1 hour before
meals
• The capsules must be kept refrigerated
• The manufacturer recommends reimmunization with
the entire 4-dose series every 5 years
• Adverse Events: minimal, if any. Include abdominal
discomfort, nausea, vomiting, fever, headache, and rash
or urticaria
Typhoid Vaccine,
Vi capsular polysaccharide vaccine
• Can be used for persons 2 years of age and
older
• One 0.5 mL (25 µg) dose administered
intramuscularly
• The manufacturer recommends a booster dose
every 2 years
• Adverse events: Minimal. Include fever (1%),
headache (1.5% to 3%), and local reaction of
erythema or induration of 1 cm or greater (7%)
Typhoid Vaccine,
Parenteral inactivated vaccine
• Not available in USA any more
• Only in children younger than 2 years of age who are at
high risk of exposure
• Immunization consists of 2 doses (0.25 mL each) given
subcutaneously at a minimum interval of 4 weeks
• Booster doses should be administered every 3 years if
continued or renewed exposure is expected
• High rate of adverse events: fever (24%), headache
(10%), and severe local pain and swelling (up to 35%)
• More severe reactions have been reported sporadically,
including hypotension, chest pain, and shock
Typhoid Vaccine
• Can we use one of these vaccines as a booster
for an other? No data have been reported
Typhoid Vaccine,
Contraindications and Precautions
• The only contraindication is a history of severe local or
systemic reactions after a previous dose
• Can we use it in pregnant women? No data
• Since the oral vaccine is a live-attenuated vaccine, it
should not be administered to immunocompromised
persons, including those known to be infected with HIV
• Immunization with Ty21a vaccine should be delayed for
at least 24 hours before or after a dose of any
antibiotic because antibiotics can inhibit the growth of
the live Ty21a strain in vitro
Thank You