Lecture 23 Francisella Brucella

Lecture 23 Francisella Brucella - Francisella and Brucella...

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Unformatted text preview: Francisella and Brucella Francisella Francisella Francisella tularemia http://mercury.bio.uaf.edu/George Happ Classification Classification Family Genus Species Subspecies Francisellaceae Francisella F. tularensis F. tularensis subsp. tularensis * F. subsp F. tularensis subsp. holoarctica F. subsp F. tularensis subsp. novicida F. subsp F. tularensis subsp. mediasiatica F. subsp Francisella tularensis Francisella tularensis Agent of tularemia a highly infectious zoonotic disease found in rodents, hares, rabbits, biting flies ,ticks and even amoeba Isolated 1911 in ground squirrels in Tulare County, CA by Francis Tularemia Rabbit Fever Deer Fever Tick Fever Deer Fly Fever Morphology & Physiology F. tularensis F. tularensis Gram negative coccobacillus Non­motile Obligate aerobe Catalase negative Prefers low temperatures Fastidious growth; requires cysteine non­pigmented non­hemolytic small, 0.2 µm x 0.2 – 0.7 µm F. tularensis F. tularensis Strains F. tularensis tularensis (Type A) Jellison Type A (subspecies tularensis ) tick­borne isolate of rabbits major US type Antigenic structure F. tularensis F. tularensis Capsule; ill defined; polysaccharide, antiphagocytic Cell wall and envelope endotoxin activity (LPS) is reduced anti­LPS antibodies can be used for serology Clinical Infection F. tularensis F. tularensis Enzootic in all areas of US Rodents and rabbits are major reservoir Adult males mainly infected Type A (subsp. tularensis) Type B (subsp. holoarctica) Highly Virulent; Focus of Bioweapons 80% of human cases less virulent; some highly virulent associated with water­dwelling rodents Live Vaccine Strain (LVS) is this subspecies Clinical Infection F. tularensis F. tularensis Humans acquire: arthropod bite (>27 species) eating infected meat (rabbit) drinking contaminated water inhaling contaminated aerosols* Varied reservoirs, vectors and ecology; still all require very few organisms to infect (1­10 cfu) Tularemia Tularemia Epidemiology Rare disease by the natural route of infection: 100 ­ 200 cases per year Mortality can range from 1­30% Farmers and landscapers in endemic areas F. tularensis F. tularensis Pathogenesis As few as one organism can cause disease in highly susceptible person Less than 10 organisms needed to infect humans via aerosol route Thought to be obligate intracellular pathogen in humans (always inside cells); primarily macrophages. Intracellular Life Cycle F. tularensis F. tularensis Oyston et al. (2004) Nature Reviews 2:967 Clinical Manifestation ­ Tularemia F. tularensis F. tularensis Ulceroglandular ­Ulcer at bite site, spread to lymph node, leading Ulceroglandular Oculoglandular to pain and swelling Oculoglandular (<5%) Typhoidal (systemic) Symptoms Oropharyngeal and Gastrointestinal; ­ingestion of contaminated meat ­ Sore throat/mouth; diarrhea, vomiting headache, chills, high fever, confusion, NO rash, NO adenopathy Clinical Manifestation ­ Tularemia F. tularensis F. tularensis Pneumonic (Inhalation) inhalation of infectious aerosols; most serious associated with high morbidity and mortality likely form for biological weapons F. tularensis F. tularensis Immunity IgM and IgG types persist but offer little immunity Cellular immunity linked to activated macrophages important to resistance; Intracellular pathogen F. tularensis F. tularensis Lab Diagnosis Culture dangerous due to possibility of lab acquired disease fastidious and slow growing Serologic Fluorescent antibody to ID organisms in tissue or serum Agglutination test most common four­fold increase in titer Treatment/Prevention F. tularensis F. tularensis Treatment Prevention streptomycin gentamicin avoid infected animals bioterrorism? Immunization individuals; Type B strain; not approved by FDA attenuated live vaccine (LVS) for high risk Bio­Containment F. tularensis Biosafety Level 2 (BSL­2) Many bacterial pathogens; benchtop Biosafety Level 3 (BSL­3) Francisella, Brucella, B. anthracis, M. tuberculosis Negative pressure room; HEPA filtered air; Biosafety cabinet Powered Air Purifying Respirator (PAPR) for aerosols Select Agents: FBI clearance, high security Biosafety Level 4 (BSL­4) Smallpox, Ebola Highly infectious agents; Space suits BSL­4 BSL­3 Bioterrorism Agents F. tularensis Category A ‘Select’ Diseases/Agents (Francisella tularensis) CDC designation of agents with highest risk to national security ­ ­ ­ Easily desseminated or transmitted person to person High mortality rates; major impact Cause public panic; require special action for preparedness Category B Diseases/Agents (Brucella species) Moderately easy to disseminate Moderate Morbidity and Low Mortality Rates Require surveillance Category C Emerging pathogens Could be weaponized Bioterrorism Agents F. tularensis WHO modeled possible use Francisella tularensis 50 kg dried Type A strain over city with 5 million people 250,000 cases 1/3 people would flee city/ 1 million require antibiotics With antibiotic treatment 10% (25,000) would require hospitalization 1% (2,500) would die due to tularemia Brucella Brucella Classification Classification Family Brucellaceae Genus Species Brucella and 2 others B. abortus B. melitensis B. suis B. canis Classification Classification Morphology & Physiology Brucella Brucella small Gram­negative coccobacilli non motile, non­hemolytic non­encapsulated require complex media to isolate; strict aerobes non fermentative, oxidase and catalase positive Pathogenicity Determinants Brucella Brucella Survival and intracellular growth is key to virulence Smooth cell wall may contribute to survival within macrophages; O­antigen of LPS Rough strains bind antibody and are less likely to survive; O­antigen of LPS Group specific proteins Cell wall carbohydrates binds to B­cells Intracellular Life­Cycle Brucella Brucella Enter through lipid rafts on host cell Inhibit fusion to lysosome Multiply in specialized organelles associated with ER Epidemiology Brucella Brucella Worldwide via animal infections (Zoonotic disease) goats, cattle, swine, sheep, reindeer, dogs, buffalo, camel, caribou, horses Animals infected via gastrointestinal tract, skin, mucous membranes, conjunctivae or infected food sources Animals recover but excrete bacteria 90% of human cases via contact with infected material (occupational hazard) Epidemiology Brucella Brucella Clinical Manifestations Brucellosis Brucella Brucella Organisms enter → access the bloodstream, lymphatics and nodes Intracellular localization within Macrophages Infected tissue become granulomatous (abscess formation) Weakness, fatigue, chills, sweat, joint and muscle pains, nervousness & mental depression Complications: Clinical Manifestations Brucella Brucella lesions in organs joint or bone infection enlarged liver Brucella Brucella Immunity IgM and IgG antibodies produced Macrophages and Monocytes are key to microbe destruction and elimination of infection; but also its means of dissemination in the body Lab Diagnosis Brucella Brucella Samples from blood spinal fluid bone marrow tissues Isolation of Brucella definitive Lab Diagnosis Brucella Brucella Culture conditions: use solid medium serum­dextrose agar serum­potato­infusion agar blood agar incubate at 10% CO2 hold for 21 – 35 days before “negative” antibiotics included to inhibit overgrowth Lab Diagnosis Brucella Brucella Serological tests: sensitive and reproducible tube agglutination test card agglutination test ELISA Treatment/Prevention Brucella Brucella Treatment tetracycline for six weeks streptomycin­tetracycline combination Prevention Control animal disease Animal vaccine usage Avoid unpasteurized milk ...
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This note was uploaded on 01/24/2011 for the course BSCI 424 taught by Professor Staff during the Fall '08 term at Maryland.

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