Tularemia (Francisella tularensis)
Purpose
To recommend procedures for handling potential
biological threats of Tularemia exposure.
Description of Agent/Syndrome
1. Francisella
tularensis, the organism that causes tularemia, is one of the most
infectious pathogenic bacteria known, requiring inoculation or inhalation of as
few as ten (10) organisms to cause disease.
2. Francisella
tularensis is considered to be a dangerous potential biological weapon
because of its extreme infectivity, ease of dissemination and substantial
capacity to cause illness and death.
3.
Francisella
tularensis is a hardy non-spore forming organism that is capable
of surviving for weeks at:
a) low temperatures in water
b) moist soil
c) hay
d) straw or
e) decaying animal carcasses
4.
F.
tularensis has been divided into two subspecies:
a) F. tularensis biovar
tularensis (Type A), which is the
most common biovar isolated in North America and may be highly virulent in
humans and animals.
b) F. tularensis biovar palaearctica (Type B) which
is relatively avirulent and thought to be the cause of all human tularemia in
Europe and Asia.
5. Human-to-human transmission has NOT been documented.
6. The United States studied use of this organism as a
weapon in the 1950s and 1960s.
7.
During World War II, the potential of F. tularensis as a biological weapon was studied by the Japanese and
by the U.S. and allies.
8.
Tularemia was one of several biological weapons that were
stockpiled by the US Military in the late 1960s. All which were destroyed by
1973. The Soviet Union continued weapons production of antibiotic and vaccine
resistant strains into the early 1990s.
Transmission
1. Naturally acquired
Natural reservoirs include
small mammals such as voles, mice, water rats, squirrels, rabbits and hares.
Naturally acquired human infection occurs through a variety of mechanisms such
as:
a) bites of infected arthropods
b) handling infectious animal tissues or fluids
c) direct contact or ingestion of contaminated
water, food, or soil
d) inhalation of infective aerosols
NOTE: F. tularensis is so infective
that examining an open culture plate can cause infection.
2.
Inhalation
Dissemination
3. Intentional (possible terrorist
action)
1. Illness
beginning three (3) to five (5) days after exposure
2. Incubation Range: One (1) to
fourteen (14) days
Signs and Symptoms
1. In the natural setting, tularemia is
noted to be a predominately rural disease.
2. Clinical presentations include:
fever, chills, headache, malaise and presents in various
forms:
a) ulceroglandular
b) glandular
c) oculogandular
d) oropharyngeal
e) pneumonic-pleuropneumonitis develops in a
significant portion of cases over days and weeks
f) typhoidal
g) septic forms-without antibiotic treatment
the clinical course could progress to respiratory failure, shock, death
Diagnosis
Rapid diagnosis relies mainly on clinical suspicion.
Culture is the only definitive diagnostic test.
1. Inform
Lab personnel of suspected Tularemia.
2. Physicians who suspect inhalational tularemia should promptly collect specimens of respiratory secretions and blood and alert the laboratory of the need for special diagnostic and safety procedures.
3. Francisella tularensis grows best in cysteine-enriched broth and thioglycollate broth and on cysteine heart blood agar, buffered charcoal-yeast agar, and chocolate agar.
4. If suspected, Lab should hold
culture for 10 days.
Treatment & Prophylaxis
|
Recommendations for treatment of Patient With
Tularemia in a Contained Casualty Setting* |
|
Contained Casualty Recommended Therapy |
|
|
Adults –
preferred choices Streptomycin,
1 g lM twice daily Gentamicin,
5 mg/kg IM or IV once daily † |
Alternative
choices Doxycycline,
100mg IV twice daily Chloramphericol,
15 mg/kg IV 4 times daily † Ciprofloxacin,
400 mg IV twice daily † |
|
Children
– preferred choices Streptomycin,
15 mg/kg IM twice daily (should not exceed 2g/d) Gentamicin,
2.5 mg/kg IM or IV 3 times daily † |
Alternative choices Chloramphericol,
15 mg/kg IV 4 times daily † Ciprofloxacin,
15 mg/kg IV twice daily † ▲ |
Pregnant
Women – preferred choices
Gentamicin,
5 mg/kg IM or IV once daily † Streptomycin,
lg lM twice daily |
Alternative choices Ciprofloxacin, 400 mg IV twice daily † |
|
Recommendations for treatment of Patient With
Tularemia in a Mass Casualty Setting and for post exposure** |
|
Mass Casualty Recommended Therapy |
|
|
Adults –
preferred choices Doxycycline,
100 mg orally twice daily Ciprofloxacin,
500 mg orally twice daily † |
Alternative choices
|
Children – preferred choices
Doxycycline
if> 45 kg, give 100 mg orally twice daily; if <45 kg, give 2.2 mg/kg
orally twice daily Ciprofloxacin,
15 mg/kg IV orally twice daily † ▲ |
Alternative
choices |
|
Pregnant Women – preferred choices Ciprofloxacin,
500 mg orally twice daily † Doxycycline,
100 mg orally twice daily |
Alternative
choices |
|
* Treatment with streptomycin, gentamicin, or ciprofloxacin
should be continued for 10 days, treatment with doxycycline or
chloramphericol should be continued for 14-21 days. Persons beginning
treatment with intramuscular (IM) or intravenous (IV) doxycycline,
ciprofloxacin, or chloramphericol can switch to oral antibiotic
administration when clinically indicated. |
|
|
† Not a US Food and Drug
Administration-approved use. |
|
|
▲Ciprofloxacin
dosage should not exceed 1 g/d in children. |
|
|
** One antibiotic,
appropriate for patient age, should be chosen from among alternatives. The duration of all recommended therapies
in second half of table is 14 days. |
|
Vaccination is NOT recommended as
post-exposure prophylaxis.
In the U.S. a live-attenuated vaccine derived from
the avirulent Live Vaccine Strain (LVS) has been used to protect laboratory
personnel routinely working with F.
tularensis.
Control Measures and Decontamination
1. Person to person transmission has
not been documented
2. Standard Precautions for patient
care and patient care equipment
3. Routine hospital disinfectants can
be used for environmental cleaning.
4. For laboratory spills, spray the surface with 10% bleach solution (1 part household bleach and 9 parts water). After 10 minutes, clean with 70% alcohol.
5. Persons with direct exposure to
powder or liquid aerosols should shower and launder clothing.
Notification
Internal: At hospital
notify______________________________
External: All suspected cases of suspected Tularemia
exposure are Class A3 Reportable and should be reported immediately to the
Local Health Department who will then contact the State Health Department
and/or CDC.
Lab:
Due to potential risks associated with handling infectious
materials, laboratory testing should be the minimum necessary for diagnostic
evaluation and patient care. Laboratory specimens should be placed in plastic
bags that are sealed, and then transported in clearly labeled, durable,
leak-proof containers directly to the specimen handling area of the laboratory.
Care should be taken not to contaminate the external surfaces of the container.
Lab personnel should be notified of what they are handling.
|
TULAREMIA
(Francisella tularensis) |
Blood
Cultures: two separate sets from different sites (one set is 2 bottles – 10
ml each bottle) |
2 red-top
or gold-top tubes (for
serology) |
Sputum |
CSF (if
meningeal signs present) |
Lymph
Node Biopsy or Aspirate (send in anaerobic transport vial) |
ID
Consult |
Note on
requisition |
|
Possible F. tularensis exposure in an
asymptomatic patient |
No |
No |
No |
No |
No |
No |
Not
applicable |
|
Tularemia |
Yes |
Yes |
Yes |
Yes |
Yes |
Yes |
R/O
Tularemia |
References
Center For Civilian Biodefense Studies: http://www.hopkinsbiodefense.org/pages/center/approach.html
Biodefense Quarterly, December 2000/January
2001-Volume 2, Number 3.
JAMA, June 6 2001-Vol 285, No.21
Tularemia Bibliography
1. American Public Health
Association. 2000. Tularemia. IN: Chin J, ed. Control of Communicable Diseases Manual. Washington,
DC: American Public Health Association; 532-535.
2. Boyce, JM. 1975. Recent trends
in the epidemiology of tularemia in the United States. Journal of Infectious
Diseases. 131: 197-199.
3. Burke, DS. 1977. Immunization
against tularemia: Analysis of the effectiveness
of live Francisella tularensis vaccine in prevention of laboratory acquired
tularemia. Journal of Infectious
Diseases. 135:55-60.
4. Christenson, B. 1984. An outbreak of
tularemia in the northern part of central Swenden. Scandinavian Journal of Infectious Diseases.
16-285-290.
5. Dennis, DT. 1998. Tularemia. In: Wallace, RB.ed. Maxcy-Rosenau-Last
Public Health and Preventive Medicine. 14th Edition. Stamford: Appleton
& Lange; 354-
357.
6. Evans, ME, Gregory, DW, Schaffner,
W, McGee, ZA. 1985. Tularemia: A 30-year
experience with 88 cases. Medicine. 64:251-269.
7. Francis, E. 1937. Sources of infection and seasonal incidence
of tularemia in man. Public Health Reports.52:103-1
13.
8. Higgins, JA, Hubalek, Z, Halouzka,
J, et al. 2000. Detection of Francisella tularensis in infected mammals and
vectors using a proble-based polymerase chain reaction. The American Journal of
Tropical Medicine and Hygiene. 62:310-318.
9. Lillite, RD, Francis, El .1937. The
pathology of tularaemia in man (Homosapiens). In: The Pathology of Tularaemia. National Institute of Health Bulletin
No. 167. Washington, DC: United States Government Printing Office: 1-81.
10. Mignani, E, Palmieri, F, Fontana, M,
Mango, S. 1988. Italian epidemic of waterborne tularaemia. Lancet.ii:1423.
11. Overholdt, EL, Tigertt, WD, KadulI,
PJ, et al. 1961. An analysis of
forty-two cases of laboratory-acquired tularemia. American Journal of Medicine. 30:785-806.
12. Pollitzer, R. 1967. History and incidence of tularemia in the
Soviet Union-A review. Institute for
Contemporary Russian Studies. Bronx, New York: Fordham University; 1-103.
13. Pullen, RL, Stuart, BM. 1945. Tularemia:
Analysis of 225 cases. Journal of the
American Medical Association. 129:495-500.
14. Russell, P, Eley, SM, Fulop, MJ,
Bell, DL, Titball, RW. 1998. The efficacy of ciprofloxacin and doxycycline against tularemia. Journal of Antimicrobial Chemotherapy. 41:461-465.
15. Saslaw, 5, Eigelsbach, HT, Prior, J,
Wilson, HE, Carhart, S. 1961. Tularemia vaccine study.lI. Respiratory challege. Archives of Internal Medicine. 107:134-146.
16. Saslaw, S, Eigelsbach, HT, Wilson,
HE, Prior, JA, Carhart, S.1961. Tularemia vaccine study.l.Intracutaneous
challenge. Archives of Internal medicine.
107:121-133.
17. Sawyer, WD, Dangerfield, HG, Hogge,
AL, Crozier, D. 1966. Antibiotic
prophylaxis and therapy of airborne tularemia. Bacteriological Reviews.
30:542-548.
18. Syrjala, H, Sutinen, S. Jokinen, K,
Nieminen, P, Tuuponen, T, Salminen, A. 1986. Bronchial changes in airborne
tularemia. The Journal of Laryngology
Otology. 100:1169-1176.
Note: These are guidelines that have been
developed with data available as of 5/9/02.
Initially Prepared by
The Akron Regional Hospital
Association
Emergency Preparedness
Subcommittee
August 20, 2002