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Biosecurity & Bioterrorism: Containing and Preventing Biological Threats
Chapter 5
Category C Diseases and Agents
Learning Objectives
Discuss the importance of HHS Category C agents.
List the most important pathogens currently found on the HHS Category C list.
Discuss the recent history of Nipah virus, hantavirus, West Nile fever virus, and the coronaviruses that are the causes of SARS and MERS.
Discuss clinical symptoms, diagnostics and treatments for Nipah virus fever, hantavirus, West Nile fever, SARS, and MERS.
Understand the challenges that public health officials and emergency management practitioners might face when an intentional release of a Category C agent occurs in their community.
Key Terminology
Emerging disease
Nipah virus fever
Hantavirus
West Nile fever
SARS
MERS
HHS Category C - Criteria
Emerging or re-emerging pathogens
High morbidity and mortality
Novel, therefore difficult to recognize, diagnose and treat
May be exploited by an adversary
A great deal of attention in the media – a new disease!
Category C Agents & Diseases
Nipah Virus
Hantavirus – HFRS & HPS
West Nile virus – West Nile Fever
Severe Acute Respiratory Syndrome (SARS)
Image courtesy CDC PHIL
Importance of Microscopy
Often no existing test
Microbiologist need to visualize the pathogen in diseased tissues
CDC plays an important role
Image courtesy CDC PHIL
Nipah Virus
Image courtesy CDC PHIL
7
Agent
Genus Henipavirus
Newly discovered virus
Related to Hendra virus
Severe, rapidly progressive encephalitis in humans
High mortality rate
Close contact with infected pigs
Severe, respiratory disease in pigs
8
History
1998-1999: Peninsular Malaysia
Human febrile encephalitis with high mortality
Cases similar to Japanese encephalitis
Discovered new virus similar to Hendra
1999: Singapore
Outbreak in abattoir workers
Pigs imported from Malaysia
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Reservoir
Flying foxes (fruit bats)
Carry the virus
Are not affected
Virus found in
Urine
Partially eaten fruit
Migratory
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Transmission
Pigs
Direct contact
Contact with body fluids
Aerosolization of respiratory or urinary secretions
No person-to-person transmission
No bat-to-human transmission
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Epidemiology
1998-1999: Malaysia
265 persons hospitalized
Many required mechanical ventilation
105 deaths (40%)
Mostly adult males - pig farmers
1.1 million pigs culled
Pig population prior to outbreak was 2.4 million
Great economic loss
Surveillance and testing
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Epidemiology
1999: Singapore
22 infected persons
Mean age 37 years old
10 asymptomatic
12 symptomatic
Encephalitis, pneumonia or both
1 death
13
Epidemiology
2004: Bangladesh
Mid-March
Faridpur District of Bangladesh
34 human cases
26 deaths
Transmission
Close contact
Exposure to common source
Image courtesy CDC PHIL
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Epidemiology
2005: Bangladesh
Tangail District
13 people lost consciousness
Contaminated palm fruit juice
One confirmed case per CDC
44 total cases, 12 deaths
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Human Illness
Incubation period: 3-14 days
Fever and headache
Encephalitis
Dizziness, drowsiness, vomiting
Seizures
Progresses to coma in 24-48 hours
Respiratory difficulty
Hypertension, tachycardia
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Human Illness
Complications
Septicemia (24%)
GI bleeding (5%)
Renal impairment (4%)
Asymptomatic
Relapse or late-onset encephalitis
Residual neurological deficits
Treatment: Supportive, ribavirin
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Disease in Animals
Pigs
Highly contagious
May be asymptomatic
Acute fever (>104°F)
Severe respiratory disease
Characteristic cough – harsh, “barking”
Neurological changes
Head pressing, agitation, aggression
Low mortality
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Diagnosis
Differentials for swine
Classical swine fever, PRRS, pseudorabies, swine enzootic pneumoniae, porcine pleuropneumonia
Diagnostic tests
ELISA
Immunohistochemistry
PCR
Virus isolation
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Nipah as a Biological Weapon
Emerging pathogen
Potentially high morbidity and mortality
Major health impact
Aerosolization potential
Economic impact
Social disruption (fear, panic)
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Hantavirus
Image courtesy CDC PHIL
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Hantaviruses
Family Bunyaviridae
RNA virus
Genus Hantavirus
Only genus not arthropod-borne
Transmitted by murid rodents
More than 25 hantavirus species
Image courtesy CDC PHIL
22
Hantaviruses
Lipid envelope
Deactivated by ordinary disinfectants
A “viral hemorrhagic fever”
Hantavirus Pulmonary Syndrome (HPS)
Hemorrhagic Fever with Renal Syndrome (HFRS)
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Hantaviruses in Our Past
American Civil War
World Wars I and II
1913, 1932
Russia reported cases
1934
Sweden - Nephropathia Endemica
1950’s
Reports of Korean Hemorrhagic Fever
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Hemorrhagic Fever with Renal Syndrome (HFRS)
1951-1954: Korean War
3,200 U.N. troops develop disease
Hantaan River separated N. & S. Korea
1977
Hantaan agent isolated and characterized
1990: 94% of serum samples from soldiers in 1950’s had antibodies
1979
Seoul virus found in Japan and Europe
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The Four Corners Outbreak
May 1993
First clinical case
Abrupt fever, myalgia, pulmonary edema
June 1993
12 fatalities
Unexplained Adult Respiratory Distress Syndrome (ARDS)
Sera cross-reacted with Hantaan, Seoul, Puumala virus
Rodents trapped - deer mouse main reservoir
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The Four Corners Outbreak
Winter and spring 1993
Drought for several years followed by snow and rain
Vegetation blossomed and rodent population grew tenfold
Virus isolated and named
Sin Nombre Virus (SNV)
Newly emerging virus has been present since 1959
38 year old Utah man
Image courtesy CDC PHIL
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Image courtesy CDC PHIL
Common Rodent Reservoirs
United States, except the Southeast
Deer mouse (Peromyscus maniculatus)
Southeast United States
Cotton rat (Sigmodon hispidus)
Rice rat (Oryzomys palustris)
Eastern
White-footed mouse (Peromyscus leucopus)
House mouse not a carrier!
Images courtesy CDC PHIL
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Transmission of Hantaviruses
Non-rodent animals may test positive
Do not excrete viral particles
Some species may introduce rodents into domestic setting
Person-to-person transmission rare
Not through blood transfusion or vectors
Southern Argentina case
Lab acquired (several cases)
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Diagnosis
Serology
ELISA used by CDC
IgM, IgG
Immunohistochemistry
Detects viral antigen in tissues
Virus isolation
Various others
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HPS Treatment
Early, aggressive intensive care
Avoidance of hypoxia
Assisted ventilation
Electrolyte balance
Maintaining normal blood pressure
Ribavirin has questionable efficacy
Careful monitoring
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Disease in Animals
Rodents
Reservoir
Asymptomatic carriers
Antigen present in virtually all organs
Infectious for life
Other mammals seronegative
33
West Nile Virus
Image courtesy CDC PHIL
34
West Nile Virus (WNV)
Flaviviridae
Flavivirus
Single stranded RNA
Related to SLE, JE, Murray Valley, Kunjin
Infects humans, birds, mosquitoes, horses and other mammals
Image courtesy CDC PHIL
35
History
1937: West Nile District, Uganda
1950
Egypt
Ecology studied
Disease varies
Israel
1951-54
1957
Meningoencephalitis in elderly
36
History
1962, 2000: France
1973-74: South Africa
1996: Romania
First outbreak in industrialized urban area
1998: Italy
1999
Russia
United States, New York
First occurrence in the western hemisphere
37
United States - 1999
New York City
62 cases
7 deaths
Zoo birds, crows, horses
St. Louis Encephalitis virus first suspected
Similar to virus strain found in Israel
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Possible Modes of Introduction of West Nile Virus into the U.S.
Infected human host
Human-transported vertebrate host
Legal
Illegal
Human-transported vector(s)
Storm-transported vertebrate host (bird)
Intentional introduction – very unlikely
39
Ecology & Transmission
Primary vector is Culex sp.
43 species
Infected mosquitoes overwinter
Transovarial transmission
Birds
Contact transmission
Migratory transport
Image courtesy CDC
40
Human Transmission
Laboratory acquired
Laceration during necropsy on blue jay
Needle stick
Blood transfusions
23 cases in 2002
Implemented screening in 2003
737 presumptive West Nile viremic donors
2 transfusion associated cases
41
Human Transmission
Organ transplantation
4 documented cases from 1 organ donor
Organ donor received blood from viremic blood donor
Transplacental transmission
WNV 27th week gestation
Breast feeding
Mother received contaminated blood
Infant WNV positive
42
Human Disease
Incubation: 3-14 days
80% asymptomatic or mild flu-like illness
20% develop sudden fever, weakness, headache, myalgia, nausea, vomiting
Symptoms last 3-6 days
Fine maculopapular rash
More frequent in children
Recent epidemics: menigoencephalitis
43
Human Disease
Less than 1% (1:150) infected
Develop severe illness
With neurological component
Encephalitis (meningoencephalitis)
Fever, confusion, disorientation, seizures, ataxia, tremors, neck stiffness, ± coma
Muscle weakness to flaccid paralysis of extremities
44
Human Disease
Severe illness
Case-fatality rate: 3-15%
Highest among elderly
Those over 50 yrs at greatest risk
Overall death rate: 0.1%
1:1,000 infections
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Diagnosis in Humans
Antibody detection
Serum or CSF
IgM capture ELISA (MAC-ELISA)
Within 8 days
Fourfold or greater rise in titer
Acute/convalescent – 3 weeks apart
Strong evidence of infection
IgM in CSF strongly suggests CNS infection
Cross reaction to other viruses
Image courtesy CDC PHIL
46
Diagnosis in Humans
Plaque reduction neutralization test
To differentiate cross-reaction
CDC test for state’s initial case
Negative tests
Collected within 14 days of illness
Reconfirm
Duration of immunity
Unknown
IgM may last 6 months or more in blood
Up to 16 months in CSF
47
Treatment in Humans
No specific therapy
Supportive care
Ribavirin - experimental
Interferon alpha-2b?
Vaccine in clinical trials
48
Critical Thinking
West Nile fever burned like a slow-moving wildfire across the United States from New York City to the California coastline in approximately four years. Clinicians, public health officials, mosquito control specialists, and animal health professionals all had to come together to mitigate the impact of this emerging disease in the United States. Although much has been done, this serious disease appears to have a foothold on U.S. soil, and cases have increased dramatically from 2006–2007. When the outbreak was first realized in 1999, some government officials were left to wonder how the pathogen made entry into the United States. Could it have been due to an intentional act?
SARS
Image courtesy CDC PHIL
50
Caused by: a new coronavirus
Origin: Guangdong Province, Hong Kong
First Appeared: November 2002
Number of Cases: 8202 (May 2003)
Fatalities: 734
Rate: 8.9%
Last Case: May 2003
Severe Acute Respiratory Syndrome (SARS)
Image courtesy CDC PHIL
51
Symptoms of SARS
Cough
High fever
Severe pneumonia
Difficult to distinguish from other respiratory diseases in early stages
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Severe Acute Respiratory Syndrome: Transmission
Spreads primarily to close contacts by direct contact
Respiratory droplets and secretions
Other infectious body fluids, secretions, and substances
Indirect contact: contaminated objects/environment
Hand hygiene and attention to contact transmission is critical
Possible airborne transmission
To date, no evidence to suggest that SARS is transmitted from asymptomatic individuals
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SARS Mysteries
Origin of SARS – animal reservoirs?
Is coronavirus the etiologic agent?
Cases without antibody
Non-cases with antibody
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SARS Mysteries (continued)
What proportion of exposed persons
develop clinical disease and death?
Proportion of exposed, infected and asymptomatic
Are there asymptomatic carriers?
Reports of cases without known source of exposure
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SARS Mysteries (continued)
What causes “superspreaders”?
Host characteristics; e.g., age
Agent characteristics – “virulent strain”
Is pathology caused by the virus or the
response to the virus?
AIDS patients appear to be resistant to SARS
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Will SARS Re-emerge?
Potential sources of re-emergence
Animal reservoir
Humans with persistent infection
Unrecognized transmission in humans
Laboratory exposure
SARS most likely to recur outside U.S.
Well-established global surveillance is important to recognition of first case
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Chapter 5 Summary
Emerging and re-emerging diseases get a lot of attention
Seemingly, they come at us “out of the blue”
New diagnostics will continue to show us the causes for “fevers of unknown origin”
May be exploited by our adversaries
Need to muster a rapid response when they arise!