Lecture: Tularemia

Introduction

 Is an uncommon potentially severe, bacterial zoonosis caused by Francisella tularensis

 Natural cycle of causative organism = maintaining of infection in wide diversity of animal host and in
certain ticks
 Transmission to human occur by sev modes
 Bites by infected ticks or other arthropods
 Direct inoculation thru skin, mucous membrane
 Handling contaminated or infected materials
 Ingestion of contaminated food or water
 Inhalation of contaminated aerosol or dust
 Agent of tularemia is widely distributed in temperate and subarctic region of North America and
Eurasia

Etiology

 F. tularensis
 Small, facultative, intracellular, Gram negative coccobacillus
 The organism = lipid envelope and able to survive under favorable conditions for sev weeks in water,
moist soils, and decaying animal carcasses
 F. tularensis strain is divided accord. to virulence testing, biochemical reaction and epidemiological
features

Type A:
 Restricted to north America
 >virulent type
 Same strain was found in Central Asia

Type B
 Found thru out Europe and N. America
 Considered to be potential agent of bioterrism because it can be ? as an aerosol and could result in
large number of ?? and because it requires special actions on medical and public health prepareness

Life cycle

 Widespread in nature
 Have been recovered from 100 sp of wild animals, 9 spp of domestic animals, numerous spp of birds
and fish and >50 spp of arthropods
 Principle natural cycle of agent involve the maintenance of infection inside wild mammalian hosts 
rodents, voles, mice, aquatic rodents (water rat)
 Certain spp of hard tick = are able to maintain infection fr 1 developmental stage to another
 Transmission among animal = accomplished:
  By the bites of blood-feeding arthropod or
 by direct exposure to contaminated materials in environment
 Human become infected:
 when they introduce into arthropod-borne cycle and r bitten by ticks or by blood-feeding fleas
or mosquitoes that had contaminated mouth part
 By handling or ingesting infected animals tissue or fluids
 By ingestion of contaminated water or food
 By inhalation of infected aerosols and dust
 The agent is ly infectious
 Require only 10 to 15 organisms to cause infection in human

Geographical distribution
 North America
 Russia
 Central Asia
 Mongolia
 Areas of near east and middle east

Population affected
 Tularemia= rural disease
 Affect person of all ages and both sexes
 Groups of highest risk:
 Hunters and travelers
 Butchers and animals skinners
 Farmers
 Person exposed with enzootic area, to bites of certain hard tick, mosquitoes

Seasonality
 Mosquito-borne transmission in rural, peaks in summer months
 The principle of pathologic changes in localized disease occur in
 Cutaneous site of inoculation
 Regional LN draining the site
 When dis = disseminated – liver, lung, skin, spleen, and LN  r most often involved
 The primary skin lesion begins as papule sev days following inoculation
 The papule rapidly progresses  vesicles that erodes and dev into ulcer which typically 2 to 3 cm
 Base of the lesion = necrotic and frequently covers w thick dark scab
 Affected LN show haem. necrosis and may suppurate
 F. tularensis response to infection – have prominent component of cell-mediated immunopatho
 The fundamental lesion – devlpmnt of granuloma
Life cycle of Francisella tularensis

Deer flies Mosquito

Lagomorphs Voles
(Rabbit)

Ticks
Ticks Water Water /
/ soil soil

Lagomorphs Voles
(Rabbit)

 Outbreak of tularemia – near Moscow (300cases) which occurs 3 y and 5y ago

 vector was mosquitoes during summer

Clinical forms of tularemia

Primary forms of tularemia includes:

1. Ulcer-glandular tularemia (45-85%)

2. Glandular tularemia (10-25%)
3. Ocular-glandular (<5%)
4. Typhoidal/septic tularemia (<5%)
5. Oropharyngeal tularemia (<5%)
6. Pneumonic tularemia (<5%)
7. Abdominal form

 incubation period 2 – 5days

 onset – sudden
 patient has
 fever (38-40°C)  myalgia
 chills  weakness
 headache  cough
 nausea  chest pain
 Types of fever in tularemia
 permanent
 remittent
 intermittent
 undular
 atypical
 without treatment = non-specific symptoms persists for sev weeks
 sweat, chill, progress weakness  characterized the continous illness
 other forms(2° form)maybe complicated by bact spread lead to secondary sepsis, tularemic
pneumonia, meningitis and other metastatic infection

Ulcer-glandular tularemia (Bubonic tularemia)

 A local papule appears at the site of inoculation the time or shortly after the appearance of fever
 can see several enlarges LN – near the site of bites
 Enlarges LN – moderately painful (<than in plague)
 During plague, √ of periadenitis
 In tularemia, no periadenitis

Ocular-glandular tularemia
 Follows the contamination of conjuctival sac
 Ulceration may occur only on the conjunctiva and regional LN =usually enlarged

Glandular tularemia
 Does not have the local cutaneous ulceration

Typhoidal tularemia
 Acute illness without localized sign
 Sepsis may occur
 SIRS  may erode

Orongpharyngeal tularemia (Anginose tularemia)

 Acquired by ingesting contaminated water or food
 Pt develop painful exudative pharyngistis sometimes with ulceration and tenderness of cervical
lymphadenopathy
 Often 1 gland affected
 The gland
 Is enlarged
 Can observes white coated gland
 Usually mistaken w diphtheria
 necessary to do bact analysis
 Diphtheria = edema of neck
 Tularemia = enlarged gland and cervical LN

Pneumonic tularemia
 Common secondary complication of other forms of tularemia
 In addition to gen. symptoms, √ pulmonary manifestation which includes:
  Cough w minimal sputum production
 Chest discomfort
 Dyspnea
 Tachypnea

Abdominal form
 Mesenteric lymphadenitis
 Pain in right epigastric
 Nausea and vomiting
 √ all symptoms of mesenteric lymphadenitis which includes :
o Padalka’s symp
o Scheternberg sympt
o Mark-federick sympt
 Other syndromes:
o Hepatolienal
o Intoxication

Diagnosis

 Clinical diagnosis – confirmed by cultural idolation of F. tularensis and diagnostic rises in serologic
titer
 1:160 or > = diagnostic for F. tularensis infection
 During tularemia = √ of enlarged LN (involved several groups) and lymphatic elements near the site
of inoculation
 In normal condition, we can’t palpate this LN
 Allergic skin testusing Tularin = diagnostic if lesion is >5mm in diameter(positive result)
 In brucellosis using Brucolin = diagnostic if lesion is >5cm in diameter (positive result) =Bjurne test

Treatment
1. Streptomycin – DOC
 Given to adults
 IM
 0.5-1.0g q12h
 For 10 days
2. Gentomycin
 Parenteral
 3-5mg/kg
 10 days
3. Tetracycline /doxycycline
4. Ciprofloxacin
 In standard dose
 For 10 days
 Combination therapy – genta +doxycycline
 Also need to use detox treatment
 Of LN is suppurative, pt needs to be refered to surgical dept for drainage