keymicrobial gilliss pan

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Key Microbial Threats: 

Key Microbial Threats Debra Gilliss M.D., M.P.H. California Department of Health Services Erica Pan, MD, MPH San Francisco Department of Public Health

Scenario: 

Scenario Thurs AM – Santa Barbara unusual case, skin involvement Thurs PM – Kern county, Bakersfield R/O smallpox Fri AM – physician Santa Barbara unusual case respiratory symptoms, bronchopneumonia and rash ? T2 or SEB Fri AM – Santa Barbara- unusual number of cases with rash, also increase in influenza cases. Fri AM – Ventura > 30 pts fever, resp, pneumonias, one traveler to China. Request for assistance. Fri noon – Kern co. Bakersfield 2 more patients with R/O smallpox. Request for assistance. Fri PM Ventura > 500 pts in Ojai, Oxnard, Ventura cities with resp sx, pneumonia, pustular rash, gram neg bacteria.

Investigation: Questions: 

Investigation: Questions Is this a case? Of what? Is this an outbreak? Is it continuing? What is the source? What is the means of transmission? When did it start? Who is at risk? What are the risks? How can it be interrupted?

Is it Bioterrorism?: 

Is it Bioterrorism? Type of agent Differences from “natural” outbreaks Unusual route of transmission Unusual number of cases Unusual population, location Lack of typical risk factors Specific threat or other contextual clues

Information Needs: Agent: 

Information Needs: Agent Route of transmission Incubation period Clinical characteristics Mode of transmission Person to person? Infectivity / Toxicity ID50, LD50 Reservoirs, vehicles Persistence in environment

Information Needs: Host: 

Information Needs: Host Symptoms and clinical course Time of onset Association with others with similar symptoms Underlying susceptibility Risk factors Possible exposures, activities Potential contacts during period of infectivity

Slide7: 

Bioterrorism Category A Anthrax (Bacillus anthracis) Botulism (Clostridium botulinum toxin) Plague (Yersinia pestis Smallpox (variola major) Tularemia (Francisella tularensis Viral hemorrhagic fevers (filoviruses [e.g., Ebola, Marburg] and arenaviruses [e.g., Lassa, Machupo]) Diseases and Agents

Criteria for Category A : 

Criteria for Category A Can be easily disseminated or transmitted from person to person; Result in high mortality rates and have the potential for major public health impact; Might cause public panic and social disruption; and Require special action for public health preparedness Previous development for biological warfare

Category B: 

Category B Brucellosis (Brucella species) Epsilon toxin of Clostridium perfringens Food safety threats(e.g., Salmonella species, Escherichia coli O157:H7, Shigella) Glanders and Melioidosis (Burkholderia mallei and pseudomallei) Psittacosis (Chlamydia psittaci) Q fever (Coxiella burnetii) Ricin toxin from Ricinus communis (castor beans) Staphylococcal enterotoxin B Typhus fever (Rickettsia prowazekii) Viral encephalitis (alphaviruses [e.g., Venezuelan equine encephalitis, eastern equine encephalitis, western equine encephalitis]) Water safety threats (e.g., Vibrio cholerae

Threat and use of Biological weapons: 

Threat and use of Biological weapons Over a dozen countries believed to be developing biological weapons, as well as innumerable fringe groups Rapid diagnosis and differentiation from natural disease phenomena are critical

Botulism: 

Botulism C. botulinum is a gram positive spore forming bacillus. Caused by toxin from Clostridium botulinum toxin types A, B, E, most commonly associated with human disease most potent lethal substance known to man (lethal dose 1ng/kg) C. butyricum and C. baratii also produce toxins

Botulism- Transmission: 

Botulism- Transmission Ingestion of preformed toxin Inhalation of preformed toxin Local production of toxin by C botulinum organisms in the gastrointestinal tract Local production of toxin by C botulinum organisms in devitalized tissue at the site of a wound

Botulism: Transmission: 

Botulism: Transmission C. botulinum spores found in soil worldwide Approximately 100 reported cases/year in the U.S. infant most common (72%) Increasing incidence of wound botulism in CA Food-borne not common No person-to-person transmission

Botulism: Clinical Forms: 

Botulism: Clinical Forms Foodborne toxin produced anaerobically in improperly processed or canned, low-acid foods contaminated by spores Wound toxin produced by organisms contaminating wound

Botulism: Clinical Forms: 

Botulism: Clinical Forms Infant Toxin produced by organisms in intestinal tract Also found in immunocompromised or post surgical adults Inhalation botulism No natural occurrence, developed as weapon One laboratory accident reported, Some animal studies

Botulism: Clinical Presentation: 

Botulism: Clinical Presentation Incubation: Ingestion 18 to 36 hours (dose dependent) Inhalation up to 72 hours Afebrile, alert, oriented; normal sensory exam Early nausea, vomiting, diarrhea Cranial Nerve symptoms Ptosis, blurry/double vision, difficulty swallowing/talking, decreased salivation

Botulism: Clinical Presentation : 

Botulism: Clinical Presentation Motor symptoms (progressive) Bilateral descending flaccid paralysis --> respiratory paralysis Death 60% if untreated; <5% if treated

Botulism: Differential Diagnoses: 

Botulism: Differential Diagnoses Neuromuscular disorders Stroke syndrome Myasthenia gravis Guillain-Barre syndrome (Miller-Fisher variant) Tick paralysis Atropine poisoning Paralytic shellfish/puffer fish poisoning Diagnosis based on clinical presentation with subsequent laboratory confirmation

Botulism: Laboratory: 

Botulism: Laboratory Serum or blood > 30 ml for mouse assay Stool, gastric contents Suspect foods Stool or wound culture for Clostridium Testing done in state lab or CDC only

Botulism: Treatment/Prophylaxis: 

Botulism: Treatment/Prophylaxis Ventilatory assistance and supportive care Botulinum antitoxin (equine) Most effective if given early Will not reverse symptoms, will prevent progression May result in serum sickness, anaphylaxis Antibiotics and drainage of wounds Infant botulism- contact CDHS

Botulinum Toxin as a Bioweapon: 

Botulinum Toxin as a Bioweapon Aum Shinrikyo 1990, 1993, 1995 Japan WW II US bioweapons program Soviet testing, gene splicing Iraq 19,000 liters weaponized ? Iran, North Korea, Syria, South Africa Source: Monterey Institute of International Studies 2002 http://cns.miis.edu/research/cbw/possess.htm

Botulinum as a Bioweapon: 

Botulinum as a Bioweapon Aerosol dispersion Food or beverage contamination Drinking water unlikely – inactivated by standard drinking water treatments Therapeutic botulinum toxin contains about 0.3% of the estimated lethal human inhalational dose and only 0.005% of the estimated lethal human oral dose; therefore, this form of toxin is not likely to be used as a bioterrorist weapon

Plague(Yersinia pestis) : 

Plague(Yersinia pestis) Gm Neg bacillus Natural vector - rodent flea Mammalian hosts rats, squirrels, chipmunks, rabbits, and carnivores Enzootic or Epizootic CDC: Wayson’s Stain of Y. pestis showing bipolar staining

Plague: Overview : 

Plague: Overview Bubonic, Pneumonic, Septicemic About 10-15 total cases/year in U.S. Mainly SW states Bubonic most common form Only 1-2 cases/yr. of pneumonic form

Plague: Bubonic: 

USAMRICD: Inguinal/femoral buboes Plague: Bubonic Incubation: 2-6 days Sudden onset headache, malaise, myalgia, fever, tender lymph nodes Clinical findings: Regional lymphadenitis(Buboes) possible papule, vesicle, or pustule at inoculation site 80% can become bacteremic 60% mortality if untreated

Plague: Pneumonic: 

Plague: Pneumonic Pneumonic From aerosol or septicemic spread to lungs Person-to-person transmission by respiratory droplet 100% mortality untreated

Plague: Pneumonic: 

USAMRICD: Pneumonic infiltrate of pneumonic plague Plague: Pneumonic Incubation: 1-3 days Sudden onset headache, malaise, fever, myalgia, cough Pneumonia progresses rapidly to dyspnea, cyanosis, hemoptysis Death from respiratory collapse/sepsis

Plague: Septicemic: 

Plague: Septicemic Primary or secondary Secondary from bubonic or pneumonic forms 100% mortality if untreated Severe endotoxemia Systemic inflammatory response syndrome Shock, Disseminated intravascular coagulopathy (DIC) Adult Respiratory Distress Syndrome (ARDS)

Plague: Differential Diagnosis: 

Plague: Differential Diagnosis Bubonic Staph/streptococcal adenitis Glandular tularemia Cat scratch disease Septicemic Other gram-negative sepsis Meningococcemia Rocky Mountain Spotted Fever (RMSF) Thrombotic Thrombocytopenic Purpura (TTP) Pneumonic Other bioterrorism threats Anthrax Tularemia Glanders, Melioidosis Other pneumonias (CAP, influenza, HPS) Hemorrhagic leptospirosis

Plague: Laboratory: 

Plague: Laboratory Sputum, blood, bubo aspirate Gram stain, culture PCR

Plague: Medical Management: 

Plague: Medical Management Supportive therapy Antibiotics Antibiotic resistant strains have been documented Isolation with droplet precautions for pneumonic plague until sputum cultures negative

Plague: Prophylaxis : 

Plague: Prophylaxis Pneumonic contacts or mass exposure Doxycycline, tetracyclines, sulfonamides, fluoroquinolones Consider antibiotic resistance Vaccine not currently available Respiratory droplet precautions

Human plague in California, 1900 - 1999: 

Human plague in California, 1900 - 1999

Slide34: 

Los Angeles, 1924

Slide35: 

October 19, 1924: woman who ran boarding house in Macy Street district, Los Angeles, died following 4 days of illness October 22: woman’s husband and nurse died October 24: several residents of Macy St. district identified ill with fever, chest & back pain, profuse bloody sputum By October 28: 18 friends and relatives of Patient #1 died of severe pneumonia October 31: pneumonic plague diagnosed from smears of lung tissue November 3: strict quarantine and rodent control measures enacted Pneumonic plague outbreak, Los Angeles 1924

The last gasp of pneumonic plague: 

November 10: total of 32 pneumonic plague cases diagnosed, 30 deaths 10 lived in Patient #1’s residence 16 were friends and relatives that visited Patient #1 Others: nurse, ambulance attendant, priest who administered last rites Index case believed to be 55 yo M with inquinal bubo on October 1 who lived two houses down from Patient #1 Total of 7 bubonic plague cases eventually identified Moribund plague-positive rat found one block away from Index and Patient #1’s residences Evidence that a rat epizootic preceded human cases: 157 of over 100,000 rats found plague-positive The last gasp of pneumonic plague

Human plague in California, 1927 - 1999: 

Human plague in California, 1927 - 1999 58 cases of plague in California residents 22 (38%) deaths prior to 1927, case-fatality = 69% Form of plague Bubonic = 39 Pneumonic (1o or 2o) = 7 Septicemic = 2 not recorded = 16

Slide38: 

Flea bite, CA ground squirrel Flea bite, chipmunk Flea bite, other rodent Domestic cat Unknown Human plague in California, 1927-1998 Exposure source

Human plague in California, 1927-1999: 

Human plague in California, 1927-1999 Exposure Season

Slide41: 

Recovered Fatal N= 58 Human plague in California, 1927-1999 Location: Plague patients were exposed in 26 California counties

Plague in domestic felids: 

Plague in domestic felids Cats are highly susceptible to plague Transmission bite from infected rodent flea contact with infected rodent (e.g., hunting) Clinical illness bubonic: fever, lethargy, anorexia, lymphadenopathy + abscessation ("buboes") septicemic: fever, shock, bleeding diathesis pneumonic: sneeze, cough, nasal discharge Fatality in untreated cats bubonic = 50-80% septic/pneumonic = ~100%

Plague and domestic felids Public health implications: 

Plague and domestic felids Public health implications Humans can be exposed to Y. pestis from plague-infected cats via inhalation of respiratory droplets contact with infectious secretions bite or scratch mechanical transportation of biting fleas

Slide44: 

Plague as a Bioweapon Japan WW II Fleas Rats General Ishii Shiro Plague outbreak Harbin, China 135 deaths in 1946

Plague (Yersinia pestis) : 

Plague (Yersinia pestis) Slides on Plague in California are courtesy of Curtis Fritz, CDHS Vectorborne disease Section

Anthrax (Bacillus anthracis): 

Anthrax (Bacillus anthracis) Bacillus anthracis –gram positive, spore forming, non-motile Produce toxins that cause tissue damage Bacteria form spores when nutrients depleted Spores can persist in soil for decades

Anthrax: 

Anthrax Transmission – direct, aerosol Reservoir – soil, infected animals LD/50 2500-55,000 spores, 1-3 spores may be sufficient for infection to occur No person to person spread

Anthrax – Cutaneous : 

Anthrax – Cutaneous Direct contact with spores Itchy papule progresses to painless black ulcer May be associated with enlarged lymph nodes Incubation period 0.5 to 12 days Case fatality low, antibiotics prevent systemic spread Differential dx – tularemia, rat bite fever, spider bite, scrub typhus

Anthrax - Inhalational: 

Anthrax - Inhalational Spores are 2-6 microns Natural spores sticky, clump Incubation 1- 43 days Spores transported by macrophage to lymph nodes Flu-like – fever, mylgia, headache Widened mediastinum, effusions Rapid deterioration, shock

Slide50: 

Anthrax: Clinical picture

Anthrax - Gastrointestinal: 

Anthrax - Gastrointestinal Ingestion of contaminated meat Incubation 1-6 days Nausea, vomiting, diarrhea, progressing to bloody diarrhea “Acute abdomen”

Anthrax- other : 

Anthrax- other Oropharyngeal Meningitis Septicemic

Anthrax – Natural occurrence: 

Anthrax – Natural occurrence Zoonotic disease of herbivores (cattle, sheep, goats, horses) exposed to spore in soil Humans - ingestion of contaminated meat, skin or respiratory exposure to contaminated materials. Rural areas worldwide Only 18 inhalation cases in U.S. between 1900- 1980 1980 Colorado rendering plant worker (cutaneous) 2000 North Dakota farmer (cutaneous) California animal cases Santa Clara October 2001 Contra Costa 1991 28 cattle infected San Luis Obispo 1984 43 cattle, 135 sheep No human cases in CA in over 20 years

Anthrax Bioterrorism: 

Anthrax Bioterrorism Sverdlovsk, Russia 1979- Initially reported as gastrointestinal form from contaminated meat. (? 250 cases, 100 deaths) Accidental release from bioweapons factory Aum Shinrikyo headquarters Tokyo 1993 (Sterne 34F2 -vaccine strain) Japan WW II - feathers

Slide55: 

Officials: Florida anthrax case 'isolated' October 5, 2001 Posted: 10:42 AM EDT (1442 GMT) WASHINGTON (CNN) -- A Florida man diagnosed with anthrax is an "isolated case," the top United States health official said Thursday, and his illness is not linked to any threats of bioterrorism.

Slide56: 

Epidemiologic Curve

Slide57: 

Environmental Information

Glanders (Burkholderia mallei): 

Glanders (Burkholderia mallei) (Farcy, Equinia, Malleus,Droes)

The Organism: 

The Organism Burkholderia mallei Gram negative bacillus Exists primarily in infected host Not found in water, soil, or plants Withstands drying for 2-3 weeks Killed by sunlight and high temp Related to Burkholderia pseudomallei Cause of meliodiosis

Host Range: 

Host Range Affects solipeds Donkeys and mules Acute form Horses Chronic form Carnivores, humans and goats susceptible Swine and cattle resistant

Transmission: Humans: 

Transmission: Humans Direct contact with infected animals Abraded skin Mucous membranes Inhalation laboratory incidents Person-to-person possible via infected secretions Incubation period 10-14 days

Who Is At Risk?: 

Who Is At Risk? Veterinarians Groomers Horsemen Butchers Lab workers

Glanders: Epidemiology: 

Glanders: Epidemiology Endemic Parts of Africa, the Middle East, and Asia Sporadic cases South and Central America Possible occurrence Balkan states and former Soviet republics Once widespread, has been eradicated in many countries

Glanders : 

Glanders 1934 Eliminated from animals the U.S. 1945 Six lab acquired cases at Camp Detrick 2000 Human case in laboratory worker at USAMRIID

Glanders: Clinical syndromes : 

Glanders: Clinical syndromes Four forms of infection Localized cutaneous Pulmonary Septicemia Chronic form Generalized symptoms Fever, malaise, muscle aches, chest pain Case-fatality rate: 95% (untreated)

Clinical Signs: Cutaneous: 

Clinical Signs: Cutaneous Incubation period: 1-5 days Erythema and ulceration of skin Lymphadenopathy Nodules Along lymph vessels Highly infectious exudate May occur through intact skin Case fatality rate: 20% treated

Clinical Signs: Septicemia: 

Clinical Signs: Septicemia Incubation period: 7-10 days Any site of infection can lead to sepsis Fever, chills, myalgia, chest pain, rash (pustular eruption) Tachycardia, jaundice, photophobia, lacrimation Rapidly fatal

Clinical Signs: Pulmonary: 

Clinical Signs: Pulmonary Inhalation of aerosolized bacteria Hematogenous spread to lungs Pneumonia, pulmonary abscesses, pleural effusion, miliary nodules

Clinical Signs: Chronic : 

Clinical Signs: Chronic “Farcy” Multiple abscesses Muscles, joints, spleen, liver Case-fatality rate: 60% Relapses common

Differential Diagnosis: 

Differential Diagnosis “The exanthematous eruption, the appearance of which is most likely a precursor of death has been mistaken for smallpox, varicella, impetigo, herpes zoster and anthrax. The general febrile state has been mistaken for typhoid, influenza, pyemia or septicemia acute rheumatism and pneumonia” Bernstein and Carling. Observations on Human Glanders, The British Medical Journal, Feb 6, 1909

Diagnosis: Humans: 

Diagnosis: Humans Culture and gram stain Sputum, urine, skin lesions, abcesses, blood Gram negative bacilli Safety pin appearance Agglutination tests May be positive after 7-10 days High background titer in normal sera makes interpretation difficult PCR

Treatment: 

Treatment Limited information on treatment Long term antibiotic treatment may be necessary No proven pre- or post-exposure prophylaxis No vaccine

Glanders as a Bioweapon: 

Glanders as a Bioweapon World War I Suspected use by Germans as biological agent to infect Russian horses and mules Affected troops and supply convoys Large number of human cases in Russia during and after WWI World War II Japanese infected horses, civilians and POW’s U.S. and Soviet Union investigated use as biological weapon. Soviet production alleged to be 2,000 metric tons/yr.

Glanders as a Biological Weapon: 

Glanders as a Biological Weapon History Very few organisms required to cause disease Easily produced Pulmonary form has high mortality Limited experience with disease can slow diagnosis and treatment

Acknowledgments: 

Acknowledgments Development of this presentation was funded by a grant from the Centers for Disease Control and Prevention to the Center for Food Security and Public Health at Iowa State University. Authors: Jamie Snow, DVM, MPH; Katie Steneroden, DVM, MPH, Radford Davis DVM, MPH

Q Fever: 

Q Fever Coxiella burnetii Rickettsial agent Stable and resistant Killed by pasteurization 1935 1st described in Queensland, Australia Found in ticks in Montana

Transmission: 

Transmission Aerosol Parturient fluids 109 bacteria per gram of placenta Urine, feces, milk Wind-borne Direct contact Fomites Ingestion Arthropods (ticks)

Transmission: 

Transmission Person-to-person (rare) Transplacental (congenital) Blood transfusions Bone marrow transplants Intradermal inoculation Possibly sexually transmitted

Epidemiology: 

Epidemiology Worldwide Except New Zealand Reservoirs Domestic animals Sheep, cattle, goats Dogs, cats Birds Reptiles Wildlife

Epidemiology: 

Epidemiology Occupational and environmental hazards Farmers, producers Veterinarians and technicians Meat processors, abattoir Laboratory workers

Q Fever in the U.S.: 2002: 

Q Fever in the U.S.: 2002 MMWR

Q Fever: Human Disease: 

Q Fever: Human Disease Incubation: 2-5 weeks One organism may cause disease Disease Asymptomatic (50%) Acute Chronic

Acute Infection: 

Acute Infection Flu-like, self limiting Atypical pneumonia (30-50%) Non-productive cough, chest pain Acute respiratory distress possible Hepatitis Skin rash (10%) Other signs (< 1%) Myocarditis, pericarditis, meningoencephalitis Death: 1-2%

Q Fever: Chronic Disease: 

Q Fever: Chronic Disease 1-5% of those infected Prior heart disease, pregnant women, immunocompromised Endocarditis Other Osteomyelitis Granulomatous hepatitis Cirrhosis 50% relapse rate after antibiotic therapy

Risk to Pregnant Women: 

Risk to Pregnant Women Most asymptomatic Transplacental transmission Reported complications In-utero death Premature birth Low birth weight Placentitis Thrombocytopenia

Prognosis: 

Prognosis Overall case-fatality rate <1 - 2.4% 50% cases self-limiting Only 2% develop severe disease Active chronic disease Usually fatal if left untreated Fatality for endocarditis: 35-55% 50-60% need valve replacement

Diagnosis: 

Diagnosis Serology (rise in titer) IFA, CF, ELISA, microagglutination DNA detection methods PCR Isolation of organism Risk to laboratory personnel Rarely done

Treatment: 

Treatment Treatment Doxycycline Chronic disease – long course 2-3 years of medication Immunity Long lasting (possibly lifelong)

Small Animal Case: 

Small Animal Case 1985, Nova Scotia, Canada 33 cases of Q fever 25 were exposed to cat 17 developed cough 14 developed pneumonia Most common symptoms Fever, sweats, chills, fatigue, myalgia, headache Cat tested positive for C. burnetii 1:152 to phase I antigen 1:1024 to phase II antigen

Prevention and Control: 

Prevention and Control Education Sources of infection Good husbandry Disposal of birth products (incinerate) Lamb indoors in separate facilities Disinfection 0.05% chlorine 1:100 Lysol Isolate new animals

Q Fever as a Biological Weapon: 

Q Fever as a Biological Weapon Accessibility Low infectious dose Stable in the environment Aerosol transmission WHO estimate 5 kg agent released on 5 million persons 125,000 ill - 150 deaths Could travel downwind for over 20 km Low mortality

Acknowledgments: 

Acknowledgments Development of this presentation was funded by a grant from the Centers for Disease Control and Prevention to the Center for Food Security and Public Health at Iowa State University. Authors: Radford Davis, DVM, MPH, Glenda Dvorak, DVM, MS, MPH, Ann Peters, DVM, MPH

Tularemia: 

Tularemia aka: Rabbit fever, Deerfly fever, Ohara’s disease, Francis disease Source Bacterium: Francisella tularensis Main Subspecies: tularensis (type A), holarctica (type B) Gram neg. coccobacillus 1st discovered in Tulare, CA in 1911-2 Reservoirs: rabbits, rodents and less commonly type B in beavers, muskrats, and voles Vector-borne: ticks - Dermacentor variabilis, D. andersonii, Amblyomma americanum deer flies - Chrysops discalis (less common)

Slide95: 

http://www.ent.iastate.edu/imagegal/ticks/aamer/aamerfanddvarf.html

Tularemia - transmission: 

Tularemia - transmission Transmission by several routes: Direct contact Inhalation Ingestion Biologic or mechanical transmission by arthropods No person-person transmission Large dose (up to 108) needed orally As few as 10 organisms needed by inoculation or inhalation May survive for 3-4 mos in water, mud, or dead animals Resistant to freezing

Tularemia Epidemiology: 

Tularemia Epidemiology > 50% of cases in the U.S. in Arkansas, Oklahoma, & Missouri ~150-300 cases/yr in the U.S. From 1980-1999, an average of 4 cases/yr (range 0-11 cases) in CA 18 cases in last 10 yrs Often occurs in cases in occupations working with animals CDBrief Wk30 (7/28/04): 2 pediatric cases in SF Bay Area in June-July Contra Costa & Alameda County residents One camped in S. Mateo Both with cervical lymphadenitis Both found ticks on face or head 3d prior to onset

Tularemia – Clinical : 

Tularemia – Clinical Syndromes: Ulceroglandular (75-85%) Glandular Oropharyngeal Pneumonic Typhoidal (5-15%) Oculoglandular Incubation period: 3-15 days Mortality: <10% treated, 20-30% untreated

Tularemia-Dx: 

Tularemia-Dx Differential diagnoses: Plague Anthrax Cat scratch disease Q fever Laboratory Diagnosis: Gram stain/culture of blood, sputum, gastric aspirates, and/or node Serology 4-fold increase Fluorescent Ab (FA) Culture                                                                           Dennis et al, JAMA consensus statement 2001

Tularemia – Tx & Prophylaxis: 

Tularemia – Tx & Prophylaxis Antibiotics Streptomycin* x 10 days Gentamicin Doxycycline, chloramphenicol, cipro Prophylaxis of potentially exposed: Rx with doxy or ciprofloxacin x 14 days (Or fever watch if some exposed already ill) Vaccination for high risk groups (laboratory workers)- IND under FDA review *Treatment of choice Dennis DT, Inglesby TV, Henderson DA, et al. JAMA 2001

Tularemia and BT: 

Tularemia and BT Incorporated into US biological warfare program in 1950s-60s Stockpile destroyed with others in 1972 Other countries are also suspected to have weaponized Studied by Japanese 1930s-40s ? Of intentional release during WWII Soviet Union thought to continue research into 1990s Could theoretically be stabilized and delivered in “wet” or “dry” form WHO estimate: If 50 Kg of F. tularensis particles aerosolized over a city of 5 million 250,000 ill 19,000 deaths

Tularemia & BT: 

Tularemia & BT Aerosol release would likely result in: Abrupt onset of large #s of acute, febrile, Flu-like illness ~3-5 days post release Significant proportion would develop pleuropneumonitis CDC estimates $5.4 billion/100,000 persons exposed

Brucellosis: 

Brucellosis Aka: Undulant Fever, Malta Fever, Mediterranean Fever, Rock Fever of Gibraltar, Gastric Fever Source Bacterium: Brucella melitensis, B. suis, B. abortus, B. canis, and others Gram neg. coccobacillus 1st described by Hippocrates in 450 BC 1st described by Sir David Bruce in 1887 Environmental persistence Temp, pH, humidity Frozen and aborted materials Center for Food Security & Public Health Iowa State University 2004

Brucella - Epidemiology: 

Brucella - Epidemiology Occupational exposure: Cattle ranchers/ dairy farmers Veterinarians Abattoir workers Meat inspectors Lab workers Hunters Travelers ~ 100 cases/yr reported in US <0.5 cases/100K people Most cases from California, Florida, Texas, & Virginia ~20-40 cases/yr in CA Classically associated with consumption of unpasteurized dairy products Many cases associated with consumption of foreign cheese

Brucella-Transmission: 

Brucella-Transmission Conjunctiva or broken skin contacting infected tissues Blood, urine, vaginal discharges, aborted fetuses, placentas Ingestion Raw milk & unpasteurized dairy products Rarely through undercooked meat Inhalation of infectious aerosols Pens, stables, slaughter houses Inoculation with vaccines Conjunctival splashes, injection Person-to-person transmission is very rare Center for Food Security & Public Health Iowa State University 2004

Brucella - Clinical: 

Brucella - Clinical Incubation varies 7-21 days to several months Acute <8 weeks from onset “flu-like” symptoms Undulant <1 yr from onset undulant fevers, arthritis, and epididymo-orchitis in males 2-5% with neurologic sxs Chronic > 1 yr from onset chronic fatigue syndrome, depression, and arthritis Most have cyclical fever Any organ system can be infected Osteoarticular Hepatomegaly GI, GU involvement Neurological

Brucella - Diagnosis & Rx: 

Brucella - Diagnosis & Rx Culture of blood, BM, or other tissue Keep for 8 weeks Serology 4X increase in titer from convalescent to acute Immunofluorescent stains Treatment: Combination Rx Doxycycline and: Rifampin x 6 weeks OR Streptomycin for 2-3 weeks Endocarditis and CNS Rx 6-9 mos Prophylaxis Vaccines for livestock Post inadvertent inoculation with vaccine strain -> Doxy x 21 days

Brucella & BT: 

Brucella & BT 1954, Brucella suis first weaponized by the United States, stockpile destroyed in 1969 Inhalation of 10 to 100 bacteria is sufficient to cause disease Large aerosol doses may shorten the incubation period and increase the clinical attack rate 2-5% mortality untreated USAMRIID

Aersolized Brucella Scenario: 

Aersolized Brucella Scenario Aerosolized B. melitensis City of 100,000 people Inhale 1,000 cells (2% decay per min) Case-fatality rate of 0.5% 50% hospitalized for 7 days Outpatients required 14 visits 5% relapsed Results 82,500 cases requiring extended therapy 413 deaths $477.7 million in economic impact Center for Food Security & Public Health Iowa State University 2004

Slide112: 

Ebola Marburg

Viral Hemorrhagic Fevers: 

Viral Hemorrhagic Fevers Severe multisystem involvement Damage to vascular system Symptoms are often accompanied by hemorrhage including petechiae, conjunctivitis, and ecchymosis

Viral Hemorrhagic Fevers: 

Viral Hemorrhagic Fevers 4 Virus families: Arenaviruses Filoviruses Flaviviruses Bunyaviruses All RNA viruses lipid envelope

Slide115: 

Classification of VHF Center for Food Security & Public Health Iowa State University 2004

Slide116: 

                                                                                                       Borio, et al JAMA consensus statement 2002

VHF Transmission: 

VHF Transmission Flavivirus Arthropods Bunyavirus Dependent on virus Aerosol Contact with infected animal tissues Mosquitoes and ticks Filovirus Unknown source in nature Direct person-to-person contact Nosocomial Aerosol Not thought to occur

VHF Transmission (cont): 

VHF Transmission (cont) Arenavirus Contact with infected rodent species Excretions Secretions Contact with secretions in laboratories

VHF Epi: 

VHF Epi Geographically restricted to areas where host species live Humans not the natural reservoir Arthropods or animals are natural host Person-to-person transmission can occur

VHF Clinical: 

VHF Clinical Incubation period: 4-35 days Symptoms vary by virus: marked fever fatigue dizziness muscle aches loss of strength exhaustion/prostration Severe: subcutaneous bleeding: petechiae hemorrhage DIC Most severe: shock CNS: coma, delirium, & seizures HFRS associated with kidney failure

Slide121: 

Borio, et al JAMA consensus statement 2002 Maculopapular Rash in Marburg Disease Ocular Manifestations in Bolivian Hemorrhagic Fever

Slide122: 

Mortality Rates Arenaviridae Argentine and Bolivian 10-30% Lassa 30-40% Bunyaviridae Rift Valley fever 1% Congo-Crimean 13-50% Flaviviridae Yellow fever less than 1% Filoviridae Marburg 23-25% Ebola 25-100% (88% in 2003 OB)

VHF Diagnosis: 

VHF Diagnosis Primarily clinical Lab: Serology PCR IHC Viral isolation Electron microscopy Only CDC or U.S. Army Medical Research Institute of Infectious Disease (USAMRIID) Notify local lab for processing check CDC Special Pathogens Branch website for specimen submission instructions http://www.cdc.gov/ncidod/dvrd/spb/mnpages/specimen.htm

VHS Tx & Infection Control: 

VHS Tx & Infection Control Supportive Tx avoid unnecessary procedures, IVs Isolation Strict contact isolation Strict respiratory isolation Strict bodily fluid isolation Decontamination: hypochorite bleach or phenolic disinfect. Ribavirin Not approved by FDA Effective in some individuals Arenaviridae and Bunyaviridae only Convalescent-phase plasma Argentine HF, Bolivian HF and Ebola

VHF Prophylaxis: 

VHF Prophylaxis Only licensed VHF vaccine - yellow fever Prophylactic ribavirin may be effective for: Lassa fever Rift Valley fever CCHF possibly HFRS (only under IND protocol).

VHF as Bioweapons: 

VHF as Bioweapons Weaponized by: former Soviet Union +/-Russia Marburg, Ebola, Lassa, & Arenaviruses until ’92 Quantified aerosol infectivity of Marburg US Yellow fever, Rift Valley fever N. Korea may have weaponized Yellow fever Aum Shinrikyo (Japanese cult) unsuccessfully attempted to obtain Ebola Borio, et al JAMA consensus statement 2002

VHF & BT: 

VHF & BT Outbreak of undifferentiated febrile illness 2-21 days following attack Could include Rash, hemorrhagic diathesis and shock Diagnosis could be delayed Unfamiliarity Lack of diagnostic tests Treatment with ribavirin may be beneficial Center for Food Security & Public Health Iowa State University 2004

VHF & BT: 

VHF & BT Most VHFs are not stable in dry form Most have uncertain stability and effectiveness in aerosol form Arenaviruses, Ebola, Marburg, and Lassa have tested effectiveness in aerosol form Marburg and Ebola high case fatality rate Rift Valley most stable VHF in liquid or frozen state VHFs do pose a threat as aerosolized agents Center for Food Security & Public Health Iowa State University 2004

BT Threat Agents Endemic to California: 

BT Threat Agents Endemic to California

Scenario: 

Scenario Major convention, large city Warnings about unusual influenza strain Outbreak respiratory illness, deaths All laboratory cultures negative Media attention critical to public health

Legionnaires disease, 1976: 

Legionnaires disease, 1976 They had tried putting samples from the Legionnaires blood and tissues in petri dishes filled with standard fluid media used to grow hundreds of other bacterial varieties – nothing happened. “At that point we figured we were dealing with a virus, McDade explained so we tried to culture it in medium with antibiotics.” it wasn’t until they injected samples into eggs not treated with antibiotics…that they saw clear evidence that living organisms inhabited the bodies of the deceased human beings. Laurie Garret, The Coming plague 1994

“Super bugs” bioengineering: 

“Super bugs” bioengineering Multiple- antibiotic resistance strains Francisella tularensis, Bacillus anthracis Burkholderia mallei, Yersinia pestis Vaccine resistant – B. anthracis Bacteria with toxins Myelin toxin attached to Yersinia pseudotuberculosis, Yersinia pestis, Legionella Virus carriers- Vaccinia with VEE and Ebola Ken Alibek, Biohazard, 1999

Slide136: 

San Francisco Serratia marcescans outbreak Eleven cases onset Sept 29, 1950- February 21, 1951 Special report No. 142 Biological Warfare Trials at San Francisco, California, 20-27 September, 1950. “the ships carrying the aerosol generating equipment moved from north to south during the release period, establishing a line source 2 or more miles offshore…” Agents were S. marcescans and B. globigii. Cole, 1988 Clouds of Secrecy

“Threats”: 

“Threats” Naturally occuring outbreaks – pandemic influenza New encounters – WNV, Legionella, Monkeypox New organisms – SARS, Nipah virus Small intentional outbreaks Inadvertant outbreaks – research, labs Large scale attack

Approach to Unknown or Novel agent: 

Approach to Unknown or Novel agent Use epidemiology! Ask the right questions Gather the right information Compare with known syndromes Use laboratories Be aware of veterinary, vector issues Remain open-minded

Slide139: 

We look on this period and think, 'Please, can we get back to the good old days,' " she said. "My message today is: The good old days are gone. This is the new normal." Julie Gerberding CDC Fourth International Conference on Emerging Infectious Diseases in Atlanta, March 1, 2004

Slide140: 

Hang in there….we’re almost done...

Scenario (This is a drill): 

Scenario (This is a drill) Thurs AM – Santa Barbara unusual case, skin involvement Thurs PM – Kern county, Bakersfield R/O smallpox Fri AM – physician Santa Barbara unusual case respiratory symptoms, bronchopneumonia and rash ? T2 or SEB Fri AM – Santa Barbara- unusual number of cases with rash, also increase in influenza cases. Fri AM – Ventura > 30 pts fever, resp, pneumonias, one traveler to China. Request for assistance. Fri noon – Kern co. Bakersfield 2 more patients with R/O smallpox. Request for assistance. Fri PM Ventura > 500 pts in Ojai, Oxnard, Ventura cities with resp sx, pneumonia, pustular rash, gram neg bacteria.

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