التولاريميا

Tularaemia is a zoonosis - an infection which can be spread from animals to humans to cause an acute, febrile, granulomatous infection. It is caused by the bacterium Francisella tularensis which can infect many animals, especially small rodents, rabbits and hares¹. F. tularensis is very infectious and requires as few as ten organisms to initiate human infection².

Attempts have been made to develop tularaemia for biological warfare and these have focused on the airborne dispersal route³.

علم الأوبئة⁴

• F. tularensis is distributed across the Northern Hemisphere.

• There are two types of the bacterium, both of which can infect humans¹:
  

  • Type A infections occur naturally only in North America. Type A infects animals and ticks and can be fatal in humans.

  • Type B causes milder symptoms than type A and does not cause fatal infections. Type B occurs in animals throughout the northern hemisphere, including North America.

• In Europe, the number of human cases is approximately 1,200 each year.

• Countries with the highest incidence rates in Europe include Finland, Sweden, Hungary, the Slovak Republic, Serbia, Montenegro, the Czech Republic and Bulgaria.

• In Europe, tularaemia has not occurred in Iceland, Ireland or Great Britain. There are some countries where the disease has not been reported, although probably does occur, including Albania, Greece, Romania, Belgium, Luxembourg and Portugal.

نقل الحركة⁵

• Tularaemia is primarily a disease of a wide variety of wild mammals and birds. Humans become infected mainly:
  

  • Through the bite of arthropods, particularly ticks and mosquitoes.

  • Through the skin, conjunctival sac or oropharyngeal mucosa, by direct contact with infected animals or animal materials.

  • By ingestion of contaminated food or water or inhalation of contaminated dust or aerosols.

• F. tularensis is easily transmitted by aerosols and inhalation of only a few organisms is likely to cause infection. Person-to-person transmission has not been documented.

عرض⁶

There are six well-recognised clinical forms:

Ulceroglandular tularaemia

• Approximately 80% of cases.

• Infection is usually via a scratch or abrasion which causes an ulcerated skin lesion at the site of entry and is associated with painful regional lymphadenopathy.

Glandular tularaemia
Similar to the ulceroglandular form except for the absence of the characteristic skin lesion.

Oculoglandular tularaemia

• Accounts for 1-2% of patients.

• The organism enters via the conjunctivae, causing a unilateral, painful, purulent conjunctivitis with submandibular, preauricular, and cervical lymphadenopathy.

Oropharyngeal tularaemia

• This is a rare form; infection occurs from eating poorly cooked meat of an infected rabbit.

• It usually presents with a sore throat (pharyngotonsillitis with regional adenopathy), abdominal pain (mesenteric lymphadenopathy), nausea, vomiting, diarrhoea and occasionally frank gastrointestinal bleeding from intestinal ulcerations.

Pneumonic tularaemia

• Primary lung infection is rarely acquired naturally but may develop in laboratory workers.

• However, pneumonia may develop after haematogenous spread in 10-15% of patients with ulceroglandular tularaemia and in 30-80% of those with typhoidal tularaemia.

• It usually presents with a dry cough, dyspnoea and pleuritic chest pain.

• Chest examination may be normal.

• Lobar pneumonia and/or adult respiratory distress syndrome may develop.

Typhoidal (septicaemic) tularaemia

• This accounts for 10-15% of tularaemia cases.

• It is more severe and patients present with fever, chills, myalgia, malaise and weight loss.

• Those affected often have pneumonia. Ulcers and lymphadenopathy are usually absent.

Other possible manifestations
These include acute kidney injury, abnormal LFTs, and rhabdomyolysis.

Rare manifestations
These include osteomyelitis, pericarditis, peritonitis, endocarditis, and meningitis.

الأعراض

Symptoms usually develop 2-5 days after infection but the incubation period can be as short as one day or as long as three weeks. Natural infection can result in a variety of symptoms:

• Ulcers: these are common and occur either at the site of an infected insect bite, or sometimes on the surface of the eye following exposure to airborne bacteria. The ulcers may be accompanied by swollen lymph nodes, general aches and fevers.

• Sore throat, pharyngitis or tonsillitis: after consumption of contaminated food or water.

• Less commonly, acute flu-like illness, often with diarrhoea and vomiting, can occur following inhalation or ingestion of bacteria.

• Pneumonia and blood poisoning: these are the most serious (and least common) natural forms of the disease (but the most likely to occur following deliberate airborne release). Symptoms would include sudden onset of high fever, chills, muscle aches, dry cough and weakness.

علامات

• Rash: as many as 20% of patients may have a blotchy, macular, maculopapular, or pustular rash.

• Patients have fever and possibly tender hepatosplenomegaly.

• Otherwise, physical findings vary with the clinical form of disease presentation.

التشخيص التفريقي

• الببغائية.

• Similar bioterrorism agents such as plague, pulmonary anthrax or Q fever.

• Diphtheria.

• Tick-borne diseases - eg, حمى القراد في كولورادو.

• Systemic fungal infections.

التحقيقات

• Blood tests show abnormal LFTs in approximately half of all patients⁷.

• Diagnosis is usually based on serology: detection by polymerase chain reaction allows early diagnosis⁸. Tularaemia serology tests may cross-react with السالمونيلا, Brucella, يرسينيا و Legionella species.

• F. tularensis can be isolated from blood, biopsy samples, or other bodily fluids and tissues. A specific culture medium is required to grow this organism in the laboratory⁷.

• F. tularensis is highly infectious to laboratory staff, so infection control precautions are required⁷.

• Skin testing may detect a cellular immune response and is both sensitive and specific (but skin test antigens are not commercially available).

الإدارة

• Symptomatic and supportive care for accompanying conditions (eg, osteomyelitis, pericarditis, peritonitis) as clinically indicated.

• Antibiotic eradication: recommended treatment for tularaemia is either a ten-day course of streptomycin (drug of choice) or gentamicin².

• Other antibiotics used to treat tularaemia include doxycycline, and ciprofloxacin ⁹.

المضاعفات

• الالتهاب الرئوي

• خراج الرئة

• فشل الجهاز التنفسي

• انحلال الربيدات

• إصابة الكلى الحادة

• نفث الدم

• التهاب السحايا

• التهاب الشغاف

التكهن⁷

• Type B generally causes a milder illness, which can occasionally be symptom-free.

• Type A causes more severe disease, causing death in 5-7% of untreated patients.

• Although symptoms may last for several weeks, most patients who receive appropriate treatment recover completely.

الوقاية

• Prevention of naturally occurring disease depends largely on:
  

  • Avoiding tick bites: wear trousers and long-sleeved shirts; use tick repellents and frequent inspection for evidence of ticks. Remove ticks promptly but take care not to squeeze the body because tick secretions may be infectious.

  • Wear gloves when exposure to dead or wild animals is necessary (eg, skinning or eviscerating a rabbit carcass).

  • Wild animal meats must be cooked thoroughly before consumption.

  • Frequent and thorough hand washing is also advised.

• Streptomycin, gentamicin, doxycycline or ciprofloxacin are recommended for post-exposure prophylaxis and must be taken for at least 14 days².

• A vaccine could be the most efficient way to prevent infection in the event of bioterrorism but an officially approved vaccine with both efficacy and safety has not yet been developed¹⁰.