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• Acute zoonotic illness caused by Francisella tularensis.

• F. tularensis Gram-negative bacillus, aerobic.


• Non-spore forming & non-motile.
• Considered a potential agent in bioterrorism by CDC.
• Important to maintain clinical suspicion as symptoms
can vary depending on the route of infection.
HISTORY
 Tularemia infections reported throughout the northern
hemisphere.
 Infection occurs most often during warmer summer months
and early fall via tick or fly bite or handling of infected animal
tissue.
 In the United States, infection is reported most frequently in
the south central states of Arkansas, Missouri, and Oklahoma.
 Tularemia is most commonly reported in children, with an
increased rate of infection in males, particularly in adolescence
and adulthood.
STATISTICS
The number of reported cases of tularemia in US (2001-2010):
• Direct Contact
• Vectors
• Ingestion
• Inhalation
Transmission
 Vector-borne
 Ticks
○ Transovarial transmission
○ 14 species
 Dermacentor andersonii
 Dermacentor variabilis
 Amblyomma americanum

 Mosquitoes, flies
○ Infrequent
 Chrysops discalis (deer fly)
Transmission
 Direct
 Contact with tissues of rabbits or other infected
mammals
○ Skinning, necropsy
○ Handling contaminated skins, paws
Ingestion
Undercooked meat
Contaminated water
Transmission
 Aerosol
 Contaminated dust
(hay, grain, soil)
○ Farmers
 Laboratory testing
○ Accidental exposures

 Not person-to-person
Transmission
 Infectious dose
 Small for inoculation or inhalation (10-50
organisms)
 Large for oral (108 organisms)
Human Disease
 Incubation
 3 to 15 days
 Six disease forms in humans
 All forms start with:
 Sudden fever
 Chills
 Headache
 Myalgia
Human Disease
 Ulceroglandular
 Most common
 Ulcer and regional lymphadenopathy
○ Ulcer 1 week-months

 Glandular
 Regional lymphadenopathy, no ulcer
 Second most common
 75-85% of all cases
Human Disease
 Oculoglandular
 Conjunctiva infected
○ By contaminated fingers
○ Contaminated material splashed into eye
 Conjunctivitis
 Regional lymphadenopathy
 Severe form
○ Ulceration of conjunctiva
○ Ocular discharge
Human Disease
 Oropharyngeal
 Ingestion
○ Hand-to-mouth
○ Consumption of undercooked meat or water
 Pharyngitis, diarrhea, abdominal pain,
vomiting, GI bleeding, nausea
Human Disease
 Typhoidal
 Acute
 Septicemia
○ Without lymphadenopathy or ulcer

 Pulmonary
 Inhalation of aerosol
 Spread through bloodstream
 Complications from other forms
 Case-fatality (untreated): 30-60%
Wildlife Disease
 Usually found dead
 Rabbits and hares
 Weakness, fever, ulcers, abscesses,
lymphadenopathy
 Behave strangely
○ Easily captured because they run slowly
○ Rub their noses and feet on the ground
○ Muscle twitches
○ Other: anorexia, diarrhea, dyspnea
Large Animal Disease
 Sheep
 Outbreaks in enzootic areas
○ Following severe winter
○ Heavy tick infestations
 Fever, weight loss,
lymphadenopathy, dyspnea,
diarrhea, isolate from flock,
rigid gait
 Death in young
Large Animal Disease
 Equine
 Fever, depression,
dyspnea, ataxia,
stiffness, limb edema
 Swine
 Latent infection in adults
 Clinical signs in young
○ Fever, dyspnea, depression

 Bovine
 Appear to be resistant
Companion Animal Disease
 Cats
 Fever, depression, anorexia
 Listlessness, apathy
 Ulcerated tongue and palate
 Dogs
 Fever, anorexia, myalgia
 Ocular and nasal discharge
 Abscess at site of infection
Pathogenesis:
 F. tularensis is a facultative intracellular bacteria,
which is able to infect numerous cell types such as
dendritic cells, neutrophils, hepatocytes, alveolar
macrophages, endothelial cells, and fibroblasts.
However, it replicates in vivo mainly in macrophages.
 F. tularensis is captured by macrophages whose
membrane forms large loops or pseudopodia
 This mechanism is also dependent on actin
polymerization.
Efficient uptake of F. tularensis by human
macrophages is dependent on the presence of
serum
Center for Food Security and Public Health, Iowa
State University, 2011
Epidemiology
 Northern hemisphere only
 North America
 Europe
 Russia
 China
 Japan

Center for Food Security and Public Health, Iowa


State University, 2011
Tularemia in the U.S.

Center for Food Security and Public Health, Iowa


State University, 2011
Tularemia in the U.S.
 Sources of infection
 Endemic areas
○ Ticks, rabbits
 Western U.S.
○ Biting flies, ticks

 Texas, 2011
 Serological evidence of infection identified in
feral swine

Center for Food Security and Public Health, Iowa


State University, 2011
 Case Incidence

 The highest incidence of cases was in 1939, when 2,291 cases


were reported
 The number remained high throughout the 1940’s
 Declined in 1950’s to the relatively constant number of cases it
is now—less than 200 per year
 Most cases occur in rural environments; rarely do they occur in
urban settings
 During the 1930s, 2000 or more cases were reported annually
 During the 1990s, mean number of cases is 124. This number
does not reflect actual incidence, since many cases are either
not reported or not accurately diagnosed. Also, some strains
have a benign nature.
 Between 1985 and 1992, 1409 cases and 20 deaths were
reported in the US, for a mean of 171 cases per year, and a
case fatality of 1.4%

Center for Food Security and Public Health, Iowa


State University, 2011
DIAGNOSIS
 Tularemia can be difficult to diagnose Because,
 It is a rare disease
 Its symptoms can be mistaken for others more common ,illness.
 For this reason it is important to share with your health care provider any
likely exposure such as tick and deer fly bite,or contact with sick or dead
animal
 Culture and isolation
 Definitive diagnosis
 Biological safety level III
 Serology
 ELISA, microagglutination
 Cross-reactions possible
 PCR
 Immunofluorescent staining
 Tissue samples
 Blood
MEDIA
 F.tularensis can grow on choclate agar or
buffered charcol yeast extract agar ,Media
supplemented with cystine.
 . Cross–reactions can occur with Brucella
spp., Legionella sp., Proteus OX19, and
Yersinia spp at low titer.
Tularemia chest X.ray
 May show hilar lymphadenopathy or pleural
effusion.
 Can have TB like milliary infiltrate
 Sometimes caseating granulomas or necrosis
found on lung biopsy
RADIOGRAPHICAL
PRESENTATION
 Chest X.ray PA view showing hillar
adenopathy(enlargement of pulmonary
lymph node at hilum region ) in case of
tuleremia..
 Hilum region:. a wedge-shaped depression on the
mediastinal surface of each lung, where the bronchus,
blood vessels, nerves, and lymphatics enter or leave the
viscus.
 Radio opaque area is showing:
Milliary TB
Miliary TB is a potentially fatal form of TB that results from
massive lymphohematogenous dissemination of
Mycobacterium tuberculosis bacilli.
Pleural infusion
 Water in lungs.
Treatment
 Blood tests and cultures can help confirm the
diagnosis. Antibiotics used to treat tularemia
include streptomycin
 gentamicin
 doxycycline
 ciprofloxacin
 Treatment usually lasts 10 to 21 days depending
on the stage of illness and the medication used
prognosis

Prognosis is a medical term for predicting the likely or


expected development of a disease,
 Untreated
○ <8% mortality overall (all cases)
○ Treated
○ <1% mortality overall (all cases)
Treatment for animals
 Remove ticks as soon as possible
 Proper removal technique
 Wash hands after removal
 Apply antiseptic to bite wound
 Streptomycin
 Antibiotic of choice
Prevention and control
 Education
 Personal protection (masks, gloves)
 Vector avoidance or protection
○ Ticks, flies, and mosquitoes
○ Rodents
 Thoroughly cook meat
Live attenuated vaccine
 Live virus strain (LVS)
 Pros :only effective vaccine available for
toleremia
 Cons:Does not provide 100% immunity
 Possibility of spontaneous return to
virulence
Tularemia as a
Biological Weapon
 History
 WHO estimate
 50 kg virulent F. tularensis particles aerosolized
 City of 5 million people
○ 250,000 people ill
○ 19,000 deaths

 Francisella tularensis has long been considered a


potential biological weapon. It was one of a number of
agents studied at Japanese germ warfare research
units in Manchuria between 1932-1945. It may have
been intentionally used on Soviet and German soldiers
during World War II. The U.S. military developed
weapons to disseminate F. tularensis aerosols in the
1950-60s.

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