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Arthropod-Borne Diseases. Lyme Disease (Lyme Borreliosis). Borrelia burgdorferi. Lyme disease (LD, Lyme borreliosis) - Borrelia burgdorferi, B. garinii and B. afzelii New syndrome – 1975 Cluster of arthritis cases in Lyme, Connecticut area Plasmid-encoded virulence factors
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Lyme Disease (Lyme Borreliosis) • Borrelia burgdorferi
Lyme disease (LD, Lyme borreliosis) - Borrelia burgdorferi, B. garinii and B. afzelii • New syndrome – 1975 • Cluster of arthritis cases in Lyme, Connecticut area • Plasmid-encoded virulence factors • Tick-borne, with deer, mice, or the woodrat as the natural reservoir • Tick must be attached for ~48 hours • Tick larvae (nymph) is small – may be hard to detect • Ixodes dammini in N.E. U.S.A.
Symptoms include localized rash, flu-like symptoms • Three stages • 1. Skin lesion • Erythema chronicum migrans • Skin rash, fever, stiff neck, malaise and lymphadenopathy • 2. Weeks to months later: • Cardiovascular manifestations • Neurologic changes (memory loss, mood changes, insomnia, hearing loss) • Migratory musculoskeletal pain • 3. Later Intermittent arthritis • Over a period of years or chronic • 8% develop cardiac symptoms, 15% develop neurologic symptoms and 60% develop joint disorders (autoimmune reactions)
Years later, it can cause symptoms resembling Alzheimer’s disease and multiple sclerosis with behavioral changes as well • Laboratory diagnosis • Isolation of the spirochete • PCR to detect DNA in the urine • Serological testing (ELISA or Western Blot) • Treatment with penicillin or tetracycline is effective if administered early
Plague • Yersinia pestis • Ring a ring of rosies • Pocket full of posies • Achoo, Achoo • All fall down
History • Old Testament – 1325 B.C. • Earliest documented evidence: 430 B.C. – Peloponnesian wars (1/3 -2/3 died) • Athenian Empire destroyed • 100 million killed in an epidemic in the 6th century • ~25% of European population in 14th century • 70,000 in London plague in 1665 • Hong Kong India epidemic in 1893 killed 10 million over a 20 year period • Eventually reached San Francisco in 1900 • Now established in SW USA (prarie dogs, ground squirrels, wood rats, chipmunks and mice)
Plague - Yersinia pestis • Flea-borne, from rodents • Small, Gram negative, non-motile, coccobacillus, bipolar staining • Sporadic in the U.S. (about 25 cases per year) • Bacteria survive and proliferate inside phagocytic cells • Symptoms include subcutaneous hemorrhages, fever, and enlarged lymph nodes (buboes)
Mortality rate is 50 to 70% if untreated • High fatality rate associated with septic shock (bacteremia – endotoxin – TNF-alpha and IL-1) • Virulence factors • Fraction I capsule – capsular antigen • Fibrinolysin dissemination of deeper tissue
Outer membrane proteins (YOPS) • YOP E, H, K, L and M • Encoded on a low calcium-response plasmid (LCR) • E = actin degradation • H = Trytophan phosphatase • K/L = Inhibition of phagocytosis • K/L = Inhibition of cell=mediated immune responses • M = Inhibition of platelet aggretation • V/W antigens • Suppress granuloma formation • Decrease in gamma interferon and tumor necrosis factor alpha cytokines
Lab • Grown from aspirates of buboes (bubonic plague) • Grown from sputum (pneumonic plague) • Treatment - streptomycin or tetracycline • If untreated it may invade lungs (pneumonic plague), resulting in 100% mortality if unrecognized within 12 to 24 hours • A vaccine is available for people at high risk • Short term protection • Ab production
Film: The Coming Plague – Part II • 26:14-36:00
Anthrax Bacillus anthracis
Anthrax - Bacillus anthracis • Facultative anaerobic rod, Gram positive, spore-forming • Mainly a disease of sheep, goats and cattle • Once established in an area, bacterial endospores from infected or dead animals contaminate the soil in the pasteur area for many years • Enter the animal through oral or intestinal abrasions enter bloodsteam replicate death in 2-3 days
Humans acquire skin infection by: • Handling hides: cutaneous form (Wool sorters disease - malignant pustule) • Inhaling spores: pulmonary form • Ingestion: gastrointestinal form • Causes ulcerated skin lesions or influenza-like symptoms; headache, fever, and nausea are major symptoms
Diagnosis • Gram stain: Gram positive • The cells have characteristic squared ends. • The endospores are ellipsoidal shaped and located centrally in the non-swollen sporangium. • The spores are highly refractile to light and resistant to staining.
Treatment - penicillin, usually in combination with streptomycin; other treatment possibilities are erythromycin or tetracycline; cephalosporins or chloramphenicol; ciprofloxacin • Vaccine - available for animals and persons with high occupational risk (e.g. military personnel, veterinarians)
October, 2001 –Anthrax-Tainted Letters: A Bioterrorist Attack from Within?
The Philadelphia Inquirer • Anthrax Case Heightens Alert • NBC news worker in N.Y. is fourth case(10/13/01) • Anthrax Worries Strike Deeper • Letter sent to Daschle; N.Y. baby infected(10/16/01) • New Clues on Anthrax Emerge- Mailings bear similar writing • Germ strain in Senate case called very potent(10/17/01) • Anthrax threat leads U.S. House to adjourn • In D.C., calm now a challenge(10/18/01) • N.J. Anthrax Case Offers Lead • $1 million reward is announced(10/19/01)
FBI digs up mailboxes in N.J. anthrax probe • Officials: Anthrax found in 3 cities is same strain(10/20/01) • Postal staff in region gets antibiotics • Hundreds received medicine in N.J. as FBI agents questioned residents of West Trenton for clues to an anthrax mystery(10/21/01) • Anthrax Likely in Two Deaths • Four cases suspected at a D.C. post office (10/23/01) • Anthrax taints White House mail site; inhalation form suspected in N.J. case • Mail handler near Trenton in stable condition • Traces are found at a base serving executive offices • CDC comes under fire for response to anthrax (10/24/01)
U.S. Tries to Ease Mail Fears • Public is told to be alert; masks; gloves for handlers (10/25/01) • Anthrax Found at More Federal Sites • Number to receive antibiotics increases • Bush signs law to help authorities halt terrorism (10/27/01) • Traces of anthrax are found at more federal sites in D.C. • New Mystery: N.J. victim has no postal or media ties (10/30/01) • Anthrax Reported in South Jersey • Mail facility is closed after positive test • Latest anthrax cases confusing investigators (11/1/01) • Anthrax Confirmed at Bellmawr • Spores found, mail center is closed again(11/4/01) • Postal worker heads home, sharing her spirit of survival • Anthrax search at federal sites widens (11/6/01)
The Emerging Threat of Bioterrorism • The systematic use of terror to: • Demoralize • Intimidate • Subjugate • Intentional or threatened use of viruses, bacteria, fungi or toxins from living organisms to produce death or disease in humans, animals or plants.
Agents of Bioterrorism and Biological Warfare • Anthrax (Bacillus antracis) • Plague (Yersinia pestis) • Smallpox (Variola virus) • Tularemia (Francisella tularensis) • Brucellosis (Brucella spp.) • Botulinum toxin (Clostridium botulinum) • Cholera (Vibrio cholerae) • Marburg virus
World War II Marks the Modern Era of Biological Weapons • Japanese facility – Unit 731: Scientists developing biological weapons including anthrax, cholera, plague
Gruinard Island: A Monument to the Effects of Biological Warfare • British forces test their own biological weapons • 1942: Bomb disperses anthrax spores overhead • 1971: Spores still viable • 1986: Decontamination of Gruinard Island
United States Develops Biological Weapons • 1943 – Anthrax weapons developed • 1950-60s – U.S. biological warfare program continues after WWII at Fort Detrick, Maryland • 1969 – President Nixon ends U.S. offensive biological weapons program. Defense work continues.
1972 - Biological Weapons Convention on the Prohibition and Stockpiling of Bacteriological and Toxin Weapons and their Destruction • Treaty outlaws development or stockpiling of biological weapons • Soviet Union and U.S.A. sign this treaty
1979 - Compound 19 Sverdlovsk (Ekaterinburg), Soviet Union: Aerosolized anthrax spores released accidentally, killing 68 people
Biopreparat: The Biological Weapons Empire of the former Soviet Union • Yeltsin admits the former Soviet Union had manufactured arsenals of deadly germs and diseases in violation of the Biological Weapons Convention at Obolensk and Koltsovo
“What we know about the effect of nuclear weapons is largely from studying what happened to human populations in Hiroshima and Nagasaki. What we know about anthrax is largely what we can tell from what happened in Sverdlovsk.” Richard Preston
Why Anthrax? • Robert Koch (1843-1910) • Develops Koch’s Postulates • Proves that Bacillus anthracis is the causative agent of anthrax (1876)
Anthrax Life Cycle • Entry • Clumps of dormant spores enter the animal’s body • Reproduction • Spores germinate into vegetative forms in nutrient-rich environment • Assassination • Millions of bacteria produce and secrete toxins that destroy cells • Hibernation • Deprived of nutrients by the decaying body, the bacteria sporulate and reform spores • Ambush • As the body decomposes, the spores drop into the soil and wait for an animal to inhale them – Cycle repeats itself
Virulence Factors of Bacillus anthracis:Why is B. anthracis pathogenic? • Endospores • Resistant to heat, disinfectants, UV, desiccation • Can remain dormant and survive for decades
Capsule • Layer of poly-D-glutamic acid • Protection from phagocytosis by host macrophages
Exotoxins • Protective antigen (vaccines) • Lethal toxin • Edema factor
Fear of Anthrax Attack Boosts Sales of Antibiotics • What is cipro? • Ciprofloxacin is a fluoroquinolone antibiotic • Inhibition of bacterial DNA gyrase (required for DNA replication and gene transcription) • More side effects than penicillin or doxycycline
Human Vaccine made by Bioport in Lansing, Michigan • Cell free vaccine (Anthrax Vaccine Absorbed) • Contains purified Protective Antigen from attenuated B. anthracis strains • Available only to medical personnel and those at high risk
Military Receive Anthrax Vaccine • 1991 – U.S. troops vaccinated for anthrax in preparation for Gulf War • 1995 – Iraq admits it produced 8,500 liters of concentrated anthrax as part of biological weapons program • 1998- U.S. Secretary of Defense William Cohen approves/mandates anthrax vaccination plan for all military service members • 2001 – Are supplies adequate for civilian populations?
Preparedness • Surveillance • CDC • Epidemiology • Diagnostics • Electronic communication links for hospitals, public health departments and laboratories • Some remote hospitals lack internet or FAX • Real time • Link information efficiently • Natl. Electronic Disease Surveillance System (NEDSS) underway • Medical and Public Health Response • Early warning bioterrorism systems • Faster detection methods required • Mayo clinic reports 1 hour detection test (11/5/01)
Preparedness • Stockpile drugs, vaccines and supplies • Research and Development • Genomics – ID • Vaccines • Antibiotics • Monoclonal antibodies • Anti-toxin antibodies • Anti-cytokine antibodies
Medical and Public Health Officials • “First responders” – Front lines of defense • Identify syndromes • Laboratory diagnoses • Communication • Supplies • Antibiotics • Antitoxins • Vaccines • Initiate PROACTIVE strategies and appropriate countermeasures
Collaboration at all levels • Local • State • Federal • Global
Weapons of Mass Destruction? ………….or Distraction? • The purpose of bioterrorism it to bring society to its knees by shutting down government, media, commerce and industry. • We must continually assess the evolving threat from biological weapons – the threat will change with time. • Proactive medical countermeasures may be effective deterrents.
Direct Contact Diseases • continued
Bacterial Vaginosis • Disease is sexually transmitted with polymicrobic etiology • Gardnerella vaginalis (image, previous slide) • Mobiluncus spp. • Mycoplasma hominis • Other anaerobic bacteria • Autoinfection in women from the rectum, which is inhabited by these organisms • Disease is mild but is a risk factor for obstetric infections, various adverse outcomes of pregnancy, and pelvic inflammatory disease
Diagnosis is based on fishy odor and microscopic observation of clue cells (sloughed-off vaginal epithelial cells covered with bacteria) in the discharge • Treatment is with metronidazole to kill the anaerobes necessary for continuation of the disease