Infectious Diseases in the Mediterranean and the Middle East

TULAREMIA

Aynur KARADENİZLİ, Kocaeli University, TURKEY © by author ESCMID Online Lecture Library Tularemia in the Mediterranean and the Middle East: Historical Background

Medical Hypotheses (2007) 69, 1371–1374 Tularemia: Epidemiology

 Tularemia is endemic in many parts of the world. .  It is distributed throughout Europe, North America and Mediterranean.  It has been reported also from China, Japan, Korea,© byRussia, author Iran, Israel and Turkey. ESCMID Online Lecture Library Tularemia: Global distribution

 A large outbreak of 585 people occurred associated with exposure to infected hares (1997).  Nineteen ulceroglandular cases of tularemia occurred in Spain (Crayfish- induced injuries)© by author (2000). ESCMID Online Lecture Library

Eiros Bouza and Rodriguez-Torres, 1998 Anda et al., 2001

Tularemia in Spain

 Tularemia outbreaks affected >1,000 persons.

 Number of the cases: ◦ 144 (2007-2008) ◦ 51 (2011)  The most significant risk exposures were ◦ Skinning or consumption of a contaminated hare © by author ◦ Tick bites, ESCMID◦ Specific Online environmental Lecture exposures Library Tularemia in Turkey

 Large outbreaks in Turkey

Akalin et al., 2009 Tularemia in the Mediterranean: Turkey

 Increases in cases in Bosnia and Kosovo during conflict suggest that social disruption can be a risk factor for this disease.

 The first human case of tularemia was reported in 1980 and there have been no subsequent case reports of tularemia in this country.  The highest seroprevalence was found in hunters (18%) and the lowest in health care workers© by (12%). author The seroprevalence of tularemia in people exposed to foxes ESCMID(hunting Online or eating Lecture the meat) Library (25%) was significantly higher than in others Tularemia in the Nothern Africa

 Some reports on tularemia in rabbits in 1938 (Tunisia)  A case reported from Tunusia in 2001.

 No more information on prevalence of tularemia ©in humansby author in this area!

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Anderson, J: Bull. Off. internat. Hyg. publ. 30, 2224 (1938) Tularemia: Epidemiology

 Human cases of tularemia predominate in late summer and fall, associated with arthropod inoculation and rabbits (arthropod-borne).

 In some countries,© by author tularemia is common in the winter when associated with exposure ESCMIDto infected Online rabbits Lecture and water Library (food- and water-borne). Tularemia

 Routes of infection: ◦ Bite of arthropods -ticks and mosquitoes ◦ Direct contact with infected animals or materials ◦ Ingestion of contaminated food or water ◦ Inhalation© of by contaminated author dust or aerosols. ESCMID Online Lecture Library F. tularensis in nature

 F. tularensis has the ability to spread and survive in widely differing natural environments.

 Category A agent of bioterrorism  It 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.© by author ESCMID Online Lecture Library Francisella tularensis

 γ-subgroup of proteobacteria  Members of the Francisellacae family  F. tularensis  F. novicida,  F. noatunensis  F. philomiragia  Subspecies of F. tularensis  Subsp. tularensis© by author  Subsp. holarctica ESCMID Subsp. Online novicida Lecture Library  Subsp. mediasiatica

Clinically important entities of tularemia

 The highly virulent F. tularensis subsp. tularensis (type A)

 The less virulent F. tularensis subsp. holarctica (type B) © by author

ESCMID Online Lecture Library Francisella tularensis Historical Background

Mc Coy isolated F. tularensis from infected squirrels in 1911. Dr. Edward Francis is one of the premier researchers in this field.

 Gram-negative coccobacili  Non-motile  Thin capsule

 Tularemia in humans occurs in several forms, depending on the route of infection.

 Ulceroglandular tularemia is the most common form in many countries (75 to 85% of reported cases).  Pulmonary tularemia caused by inhalation of aerosolized bacteria  Typhoidal tularemia (Mortality rates can range from© 40by to author 60% )  Oropharyngeal tularemia (77% in Turkey) ESCMID Oculoglandular Online Lecturetularemia results Library from contamination of the conjunctiva. Tularemia or Tuberculosis Granulamatous inflammation and cervical lymph node enlargement are common findings in both tuberculous lymphadenitis and oropharyngeal tularemia.

 Oropharyngeal tularemia misdiagnosed as tuberculosis.© by author

ESCMID Online Lecture Library Karabay O et al. Clin Microbiol Infect. 2013 Feb;19(2):E113-7.

Diagnosis of tularemia

 Recovery of F. tularensis from culture  Antigen detection  Molecular detection  Serology

 According to the clinical forms ◦ pharyngeal swab, ◦ fine needle lymph node biopsy, ◦ ulcer scrapings, ◦ sputum, ◦ blood and© conjunctival by author swab ESCMIDcan be usedOnline for culturing Lecture and Library PCR.

Figure 1: (a) Appearance of cervical painful lymphadenopathy (b) Appeareance of aspiration material from lympadenopathy due to tularemia

a © by author

ESCMIDTularemia: a rare cause Online of cervical lymphadenopathy. Lecture Karabay O, Karadenizli Library A, Durmaz Y, Ozturk G. Indian J Pathol Microbiol. 2011;54(3):642-3 Environmental samples: Water, carcasses, mud….

 Laboratory stuff handling the cultures of F. tularensis are at considerable risk of infection and need to take appropriate measures.

 F. tularensis is a fastidious organism due to its requirement of cysteine or cystine for enhanced growth. ◦ Francis medium, CHAB medium .

 2-10 days at 37°C in 5% CO2.  Confluent, mucoid, greenish-white colonies sometimes with an opalescent sheen or metallic sheen

 Aminoglycosides,  Tetracyclines,  Chloramphenicol  Quinolones are recommended by CLSI

◦ Broth microdilution using cation-adjusted MHB with a 2% IsoVitaleks can be used for susceptibility testing.

 The E-test method has also been utilized for this aim.

 Because of the difficulty in culturing F. tularensis, most cases of tularemia are diagnosed with serology.

 Antibody response to F. tularensis occurs about 2 weeks after the onset of the disease.  The detection of serum antibodies is most frequently achieved by agglutination or ELISA.© by author

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Other Methods for the Diagnosis of Tularemia

 A range of PCR-based assays have been used for the detection of F. tularensis. ◦ ISFtu2 ◦ Tul 4 ◦ Fop A © by author ESCMID Online Lecture Library Tularemia: Treatment

 There is no natural resistance in F. tularensis to antibiotics used for clinical therapy (aminoglycosides, tetracyclines, chloramphenicol, and quinolones).  Natural resistance to beta-lactams

◦ Erythromycin© by is notauthor used for treatment ◦ Erythromycin resistance is used as an ESCMIDepidemiological Online Lecturemarker. Library Important notes..

 Physicians and health care workers should be informed about F. tularensis.  Early warning system for epidemics is needed.  F. tularensis is still circulating in the Mediterranean© by and author the Middle East.  Studies on domestic and wild animals will ESCMIDclarify Onlinethe epidemiology Lecture of Librarytularemia in these regions.

……We need more and more information on tularemia in the Mediterranean and the Middle East countries.