Zoonotic Diseases of Non-Human Primates

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Zoonotic Diseases of Non-Human Primates
Note The images in this presentation are for
non-profit, educational use only.
Neil Grove University of North Carolina Chapel
Hill Division of Laboratory Animal Medicine
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What is a zoonotic disease?

• A zoonotic disease is one that can be transmitted
  from animals to humans or from humans to animals.

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With each disease we will attempt to answer the
following questions

• What is it?
• How do I get it?
• What are the symptoms?
• What precautions can I take to avoid getting it?

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What is the goal of this training?

• The goal is to give you a general familiarization
  with the zoonotic diseases of primary concern in
  non-human primates.
• The content of this training does not begin to
  cover all of the issues and considerations
  surrounding safely working with animals that are
  possible carriers of these diseases.

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What is our goal for this training?

• Were you to work in a facility that housed
  non-human primates, you would be trained
  extensively on all hazards involving these
  diseases and the precautions taken to avoid their
  acquisition.
• For those working with non-human primates that
  may carry these diseases, proper PPE, heightened
  awareness and alertness while working the
  animals, and following procedures can literally
  be the difference between life and death.

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What diseases will we discuss?

• Herpes B
• Tuberculosis
• Shigellosis
• Measles
• Ebola Hemorrhagic Fever
• Marburg Hemorrhagic Fever
• Hepatitis

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Herpes B What is it?

• B virus (Cercopithecine herpesvirus 1) is a
  zoonotic agent that can cause fatal
  encephalomyelitis (concurrent inflammation of the
  brain and spinal cord) in humans.(1)

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Herpes B What is it?

• B virus is a naturally occuring infectious agent
  that is endemic (disease occurs continuously and
  with predictable regularity in a specific area or
  population) among macaque monkeys (including
  rhesus and pig-tailed macaques, cynomalgus
  monkeys, and other macaques). (1)

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photo from AALAS learning library
http//pin.primate.wisc.edu/factsheets/entry/pigta
il_macaque
pigtail macaque
cynomolgus monkey
photo from AALAS learning library
photo from AALAS learning library
stump-tail macaque
rhesus monkey
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How Can You Tell Which Monkeys Carry B virus and
are shedding it?

• You cant
• B virus infection generally is asymptomatic or
  mild in macaques. (1)
• B virus infects 70 of surveyed captive adult
  macaques. (2)

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How Can You Tell Which Monkeys Carry B virus and
are shedding it?

• Although virus shedding is more frequent during
  the mating season (roughly March to June) or when
  an animal is ill, under stress, or
  immunosuppressed, there are often no signs of
  shedding. Macaques should always be regarded as
  potentially infectious.

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How are people exposed to herpes B?

• Documented routes of exposure include
• bites
• scratches
• exposure to tissue culture material
• exposure to tissue obtained during monkey autopsy
• needle stick injuries
• cage scratches
• mucosal splash
• human to human transmission

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(No Transcript)
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Symptoms

• The incubation period between initial exposure
  and onset of clinical signs ranges from 2 days to
  one month, but the time at which symptoms arise
  after exposure can vary widely. (2)

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Symptoms

• After exposure by bite, scratch, or other local
  trauma, or contamination of vulnerable sites,
  humans might develop a herpetiform vesicle at the
  site of inoculation. (2)

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Symptoms

• Early clinical signs include myalgia, fever,
  headache, and fatigue and are followed by
  progressive neurological disease with numbness,
  hyperesthesia (sensitive skin), paresthesia
  (tingling), diplopia (seeing double), ataxia
  (unable to coordinate voluntary muscle
  movements), confusion, urinary retention,
  convulsions, dyshphagia (difficulty swallowing),
  and an ascending flaccid paralysis.(lacking in
  muscle tone and tendon reflexes) (2)

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Symptoms

• Among untreated humans, the mortality rate
  associated with B virus infection is estimated to
  be 80. The mortality rate has declined since
  the advent of antiviral therapy. (1)

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Prevention/Preparation

• Employers should conduct training and periodic
  assessments to ensure that worker protection
  programs are effective. In particular, all
  employees who come into contact with macaques or
  macaque tissues should be trained about the risks
  of B virus and other infections and the
  importance of preventive measures. (4)

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Prevention/Preparation

• All macaque monkeys not known to be free of B
  virus infection should be regarded as infected
  because viral shedding is intermittent and can
  occur in the absence of visible lesions. (3)

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Prevention/Precautions

• So that baseline serum levels are available for
  comparison in the event of an exposure, the
  occupational health care provider should consider
  collecting and then storing serum samples
  obtained from primate workers at the time of
  employment.(1)

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Precautions/Prevention

• Materials including supplies used for first aid
  and specimen collection, copies of written
  instructional materials, and treatment protocols
  for exposures should be available in areas where
  exposure can occur. (1)

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Precautions/Prevention

• Workers need to be aware that any episode of
  prolonged fever (for gt48h), flulike symptoms, or
  symptoms compatible with B virus infection, even
  in the absence of a known exposure, needs to be
  reported to their supervisor and to occupational
  health care personnel. (1)

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Precautions/Prevention

• Primate workers should be given a card to carry
  in their wallet that indicates the symptoms of B
  virus infection and contact information for a
  local health care provider who is knowledgeable
  about B virus. (1)

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PPE

• Monkey handlers should wear
• leather gloves
• long sleeved garments for hand and arm protection
  (2)

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PPE

• Goggles or glasses and a mask or a chin- length
  wraparound face shield is recommended to protect
  the mucous membranes of workers in areas where
  captive macaques are located.
• Face shields or glasses with side shields must be
  able to prevent splashes to the head from running
  down into the eyes. (1)

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Case Report

• On October 29, 1997, a 22-year-old researcher at
  a primate-center field station was assisting with
  a routine group capture of rhesus macaques
  (Macaca mulatta) in a free-ranging corral.
  Personnel conducting the capture wore uniforms,
  disposable latex gloves, and surgical masks. Eye
  protection was not worn. During the transfer of
  an unidentified macaque into a squeeze cage,
  undetermined liquid from the animal entered the
  researchers eye.

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Case Report

• The worker wiped her eye at the time of exposure.
  Approximately 45 minutes later she flushed her
  eye with tap water for 23 minutes. There was no
  medical treatment or consultation at the time of
  the exposure. The researcher subsequently
  developed a Cercopithecine herpesvirus 1 (B
  virus) infection despite intensive antiviral
  therapy, she died on December 10, 1997. This
  incident is the first documented case of a B
  virus infection resulting from an ocular exposure
  to macaque secretions.

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Review Questions

• What does it mean when we say that B virus is
  endemic in macaques and that they are
  asymptomatic carriers.

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Answer

• Basically, it means that it can be assumed that B
  virus is always present among macaques, and if
  they were carrying it there is no way that you
  would know it just by looking at them.

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Question

• Under what circumstances is B virus shedding more
  frequent among infected macaques? If you were
  working with macaques, would this be the only
  time that you would worry about contracting it?

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Answer

• Virus shedding is more frequent during the mating
  season, if an animal is immunosuppressed, or
  stressed.
• You can still contract B virus at any time, these
  are simply times when virus shedding is more
  frequent.

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Question

• Why would safety glasses not be adequate eye
  protection when working with macaques?

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Answer

• Safety glasses do not fully protect the eyes from
  a splash from the side or from anything that
  could run down the head into the eyes.

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Tuberculosis

• What is it?
• Tuberculosis of animals and humans is caused by
  acid-fast bacilli of the genus mycobacterium.
• Lab animals are potential reservoirs of several
  mycobacterial species including M. tuberculosis,
  M. avium-intracellulare, M. bovis, and M.
  marinum. (2)

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Tuberculosis

• In addition to cattle, birds, and humans that
  serve as the main reservoir for these
  mycobacteria, many lab animals including
  nonhuman primates, swine, sheep, goats, rabbits,
  cats, dogs, and ferrets are susceptible to
  infection and contribute to the spread of the
  disease. (2)

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Tuberculosis

• However, nonhuman primates are of primary
  importance in the consideration of these diseases
  in the laboratory-animal environment. (2)

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Tuberculosis

• Nonhuman primates generally develop tuberculosis
  from humans during capture and exportation from
  parts of the world where the prevalence of the
  disease in humans and animals is high. (2)

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TB How do I get it?

• TB is transmitted via aerosols from infected
  animals or tissues.
• Lab animal personnel involved in the care, use,
  or necropsy of infected animals are especially at
  risk for TB. (2)

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TB How do I get it?

• Humans can contract the disease in the lab
  through exposure to infectious aerosols generated
  by the handling of dirty bedding, the use of
  high-pressure water sanitizers, or the coughing
  of animals with respiratory involvement. (2)

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TB How do I get it?

• Other potential sources of exposure include fecal
  shedding by animals with enteric infection and
  skin exudates resulting from scofuloderma or
  suppurative fistulated lymph nodes.
  Mycobacterial disease can also be spread by entry
  of bacilli into the body by ingestion or wound
  contamination. (2)

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Symptoms of TB

• Most commonly reflects involvement of pulmonary
  system.
• Characterized by cough, sputum production, and
  eventually hemoptysis (expectoration of blood
  from respiratory tract).
• Incubation period for development of demonstrable
  primary lesion or a substantial secondary skin
  reaction is 4-12 wks. (2)

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Symptoms of TB

• After that, the risk of progressive pulmonary or
  extrapulmonary disease remains highest during the
  next 1-2 yrs, but recrudescence of a latent
  infection persist for the rest of the persons
  life. (2)

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Symptoms of TB

• Extrapulmonary forms of the disease can involve
  any tissue or organ system and include
  disseminated infections of multiple organs.
• General symptoms as the disease progresses
  include weight loss, fatigue, fever, chills, and
  cachexia (general physical wasting). (2)

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Precautions/Prevention

• Facilities housing primates perform TB tests on
  all primates at least twice yearly. The test
  involves injection of a small amount of
  tuberculin (killed TB bacteria) injected
  intradermally into the eyelid of the monkey. Any
  redness or swelling at the injection site may
  indicate that the animal is infected with
  tuberculosis. (5)

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Prevention/Precautions

• Personnel education
• Periodic surveillance for infection in nonhuman
  primates and their handlers (human TB test also
  done intradermally)
• Isolation and quarantine of any suspect animals

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Prevention/Precautions

• Prompt euthanasia of infected animals
• Necropsy and microbiological and
  histopathological analysis of animals confirmed
  positive.

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Prevention/Precautions

• Personnel who convert to a positive tuberculin
  skin reaction should be evaluated further.
  Institutions should recognize the risk that such
  personnel pose for nonhuman primate populations
  it might warrant their reassignment to work with
  other animals. (2)

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Review Questions

• How do NHP generally develop TB?

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Answer

• Nonhuman primates generally develop tuberculosis
  from humans during capture and exportation from
  parts of the world where the prevalence of the
  disease in humans and animals is high

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Question

• How is a TB test administered in NHPs?

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Answer

• The test involves injection of a small amount of
  tuberculin (killed TB bacteria) injected
  intradermally into the eyelid of the monkey. Any
  redness or swelling at the injection site may
  indicate that the animal is infected with
  tuberculosis. The eyelid is used because the
  results are easily observed.

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Shigellosis

• What is it?
• Shigellosis is an infectious disease caused by a
  group of bacteria called Shigella.
• The Shigella germ is actually a family of
  bacteria that can cause diarrhea in humans.

Shigella flexneri
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Shigellosis What is it?

• There are several different kinds of Shigella
  bacteria Shigella sonnei, also known as "Group
  D" Shigella, accounts for over two-thirds of the
  shigellosis in the United States.
• A second type, Shigella flexneri, or "group B"
  Shigella, accounts for almost all of the rest.
• Other types of Shigella are rare in this country,
  though they continue to be important causes of
  disease in the developing world. One type found
  in the developing world, Shigella dysenteriae
  type 1, causes deadly epidemics there. (6)

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How do I get shigellosis?

• Nonhuman primates can harbor all three of the
  common types of shigella bacteria (S. flexneri,
  S. sonnei, and S. dysenteriae) previously listed.
  
• Nonhuman primates are the only important
  reservoir for shigellosis in the animal
  facilities, although zoonotic transmission of the
  organism from guinea pigs, other rodents, and
  dogs has been recorded under unique
  circumstances. (2)

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How do I get shigellosis?

• Shigellosis is transmitted by a direct or
  indirect fecal-oral route. Shigella spp. are
  very infectious, requiring only 10-100 organisms
  to produce infections. (2)

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How do I get shigellosis?

• Shigellosis can be transmitted from human to
  human.
• Shigella are present in the diarrheal stools of
  infected persons while they are sick and for a
  week or two afterwards.

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How do I get shigellosis?

• Most Shigella infections are the result of the
  bacterium passing from stools or soiled fingers
  of one person to the mouth of another person.
• This happens when basic hygiene and hand washing
  habits are inadequate. It is particularly likely
  to occur among toddlers who are not fully
  toilet-trained. Family members and playmates of
  such children are at high risk of becoming
  infected. (6)

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How do I get shigellosis?

• Food may become contaminated by infected food
  handlers who forget to wash their hands with soap
  after using the bathroom.
• Vegetables can become contaminated if they are
  harvested from a field with sewage in it.
• Flies can breed in infected feces and then
  contaminate food.
• Shigella infections can also be acquired by
  drinking or swimming in contaminated water. Water
  may become contaminated if sewage runs into it,
  or if someone with shigellosis swims in it. (6)

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Prevalence?

• Every year, about 18,000 cases of shigellosis are
  reported in the United States. Because many
  milder cases are not diagnosed or reported, the
  actual number of infections may be twenty times
  greater. (6)

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Prevalence?

• Shigellosis is particularly common and causes
  recurrent problems in settings where hygiene is
  poor and can sometimes sweep through entire
  communities. (6)

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Prevalence

• Shigellosis is more common in summer than winter.
  
• Children, especially toddlers aged 2 to 4, are
  the most likely to get shigellosis. Many cases
  are related to the spread of illness in
  child-care settings, and many more are the result
  of the spread of the illness in families with
  small children.
• In the developing world, shigellosis is far more
  common and is present in most communities most of
  the time.

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Symptoms

• Most who are infected with Shigella develop
  diarrhea, fever, and stomach cramps starting a
  day or two after they are exposed to the
  bacterium. The diarrhea is often bloody.
• Shigellosis usually resolves in 5 to 7 days. In
  some persons, especially young children and the
  elderly, the diarrhea can be so severe that the
  patient needs to be hospitalized. A severe
  infection with high fever may also be associated
  with seizures in children less than 2 years old.
  Some persons who are infected may have no
  symptoms at all, but may still pass the Shigella
  bacteria to others. (6)

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Precautions/Prevention

• Prevention of shigellosis in a laboratory-animal
  facility should be based on identification and
  treatment of the carrier state or disease in a
  NHP reservoir.
• Personnel should also rely on the use of
  protective clothing, personal hygiene, and
  sanitation measures to prevent the transmission
  of the disease. (6)

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Precautions/Prevention

• Some tips for preventing the spread of
  shigellosis
• Wash hands with soap carefully and frequently,
  especially after going to the bathroom, after
  changing diapers, and before preparing foods or
  beverages 
• Dispose of soiled diapers properly  
• Disinfect diaper changing areas after using them
    

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Precautions/Prevention

• Keep children with diarrhea out of child care
  settings  
• Supervise handwashing of toddlers and small
  children after they use the toilet  
• Persons with diarrheal illness should not prepare
  food for others  
• If you are traveling to the developing world,
  "boil it, cook it, peel it, or forget it
• Wash hands after removing PPE when working with
  NHPs or their caging.

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Review Questions

• How is shigellosis transmitted?

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Answer

• Shigellosis is transmitted by a direct or
  indirect fecal-oral route.

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Question

• What population of people are most likely to get
  shigellosis?
• Why?

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Answer

• Children, especially toddlers aged 2 to 4, are
  the most likely to get shigellosis.

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Measles

• What is it?
• Its a viral disease.
• Humans are the reservoir for measles. Nonhuman
  primates become infected through contact with
  human populations with endemic measles.
• Old and New World NHPs are susceptible
• Spreads rapidly through infected NHP colonies (2)

Measles virion seen through a microscope
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How do I get it?

• Measles is a highly communicable disease.
• Measles is transmitted via infectious aerosols,
  contact with nasal or throat secretions, or
  contact with fomites freshly contaminated with
  infectious secretions. (2)

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What are the symptoms?

• Clinical signs similar in NHP and humans
• In humans, fever develops after an incubation
  period of about 10d and is followed by
  conjunctivitis, coryza, cough, and Kopliks spots
  inside the mouth.

Kopliks spots
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What are the symptoms?

• Later, a characteristic exanthematous rash
  develops, beginning on the face, becoming
  generalized over the body, and ending sometimes
  in flaky desquamation.(2)

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What are the symptoms?

• Complications of viral replication or secondary
  bacterial infection can result in pneumonia,
  otitis media, diarrhea, or, rarely, encephalitis.
  (2)

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Prevention/Precautions

• As always, PPE, PPE, PPE
• Vaccination of all NHP handlers against measles
  should be ensured, and vaccination of NHP
  populations should be considered.

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Review Question

• Are New World monkeys susceptible to measles?

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Answer

• Yes both Old and New World Monkeys are
  susceptible to measles.

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Question

• True or false
• Clinical signs of measles are dramatically
  different in monkeys than in humans.

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Answer

• False - Clinical signs are similar in NHP and
  humans.

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Ebola Hemorrhagic Fever

• What is Ebola hemorrhagic fever?
• Ebola hemorrhagic fever (Ebola HF) is a severe,
  often-fatal disease in humans and nonhuman
  primates (monkeys, gorillas, and chimpanzees)
  that has appeared sporadically since its initial
  recognition in 1976. (7)

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What is it?

• The disease is caused by infection with Ebola
  virus, named after a river in the Democratic
  Republic of the Congo (formerly Zaire) in Africa,
  where it was first recognized. The virus is one
  of two members of a family of RNA viruses called
  the Filoviridae. (7)

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What is it?

• There are four identified subtypes of Ebola
  virus. Three of the four have caused disease in
  humans Ebola-Zaire, Ebola-Sudan, and Ebola-Ivory
  Coast. The fourth, Ebola-Reston, has caused
  disease in nonhuman primates, but not in
  humans.(7)

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What is it?

• The exact origin, locations, and natural habitat
  (known as the "natural reservoir") of Ebola virus
  remain unknown. However, on the basis of
  available evidence and the nature of similar
  viruses, researchers believe that the virus is
  zoonotic and is normally maintained in an animal
  host that is native to the African continent. (7)

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What is it?

• A similar host is probably associated with
  Ebola-Reston which was isolated from infected
  cynomolgus monkeys that were imported to the
  United States and Italy from the Philippines. The
  virus is not known to be native to other
  continents, such as North America. (7)

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Where is it?

• Cases of Ebola HF have been reported in the
  Democratic Republic of the Congo, Gabon, Sudan,
  the Ivory Coast, Uganda, and the Republic of the
  Congo. No case of the disease in humans has ever
  been reported in the United States. (7)

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Where is it?

• Ebola-Reston virus caused severe illness and
  death in monkeys imported to research facilities
  in the United States and Italy from the
  Philippines during these outbreaks, several
  research workers became infected with the virus,
  but did not become ill.(7)

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Where is it? Most recent case.

• Ebola hemorrhagic fever in the Republic of the
  Congo - 16 June 2005
• From 25 April to 16 June 2005, a total of 12
  cases (1 laboratory-confirmed and 11
  epidemiologically linked) including 9 deaths has
  been reported in Etoumbi and Mbomo in Cuvette
  Ouest Region. The last reported death occurred on
  26 May. (8)

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How is it contracted?

• Because the natural reservoir of the virus is
  unknown, the manner in which the virus first
  appears in a human at the start of an outbreak
  has not been determined.
• Researchers have hypothesized that the first
  patient becomes infected through contact with an
  infected animal. (7)
•  

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How is it contracted?

• After the first case-patient in an outbreak
  setting is infected, the virus can be transmitted
  in several ways
• Direct contact with the blood and/or secretions
  of an infected person.
• Contact with objects, such as needles, that have
  been contaminated with infected secretions.
• Thus, the virus is often spread through families
  and friends because they come in close contact
  with such secretions when caring for infected
  persons. (7)

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How is it contracted?

• Often transmitted in the health care setting.
• It includes both types of transmission described
  above.
• In African health-care facilities, patients are
  often cared for without the use of a mask, gown,
  or gloves. This has led to exposure of health
  care workers(7)

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How is it contracted?

• When needles or syringes are used, they may not
  be of the disposable type, or may not have been
  sterilized, but only rinsed before reinsertion
  into multi-use vials of medicine.
• If needles or syringes become contaminated with
  virus and are then reused, numerous people can
  become infected. (7)

92
How is it contracted?

• Ebola-Reston appeared in a primate research
  facility in Virginia, where it may have been
  transmitted from monkey to monkey through the
  air.
• While all Ebola virus species have displayed the
  ability to be spread through airborne particles
  (aerosols) under research conditions, this type
  of spread has not been documented among humans in
  a real-world setting, such as a hospital or
  household. (7)

93
What are the symptoms

• The incubation period ranges from 2 to 21 days.
• The onset of illness is abrupt.
• Characterized by fever, headache, joint and
  muscle aches, sore throat, and weakness, followed
  by diarrhea, vomiting, and stomach pain. A rash,
  red eyes, hiccups and internal and external
  bleeding may be seen in some patients. (7)

94
Circumstances and location of some outbreaks
between 1996 and 2002.

• Researchers do not understand why some people are
  able to recover from Ebola HF and others are not.
  However, it is known that patients who die
  usually have not developed a significant immune
  response to the virus at the time of death.(7)

95
Prevention/Precautions

• Because the identity and location of the natural
  reservoir of Ebola virus are unknown, there are
  few established primary prevention measures.
• Health-care providers must be able to recognize a
  case of Ebola HF should one appear. (7)

96
Prevention/Precautions

• Wearing of protective clothing, such as masks,
  gloves, gowns, and goggles is essential.
• Use infection-control measures, including
  complete equipment sterilization and the
  isolation of Ebola HF patients from contact with
  unprotected persons. (7)

97
Prevention/Precautions

• The aim of all of these techniques is to avoid
  any persons contact with the blood or secretions
  of any patient.
• If a patient with Ebola HF dies, it is equally
  important that direct contact with the body of
  the deceased patient be prevented. (7)

98
Prevention/Precautions

• Lab animal workers must always wear appropriate
  PPE.
• The fact that Ebola Reston was found in the US
  should heighten lab animal workers awareness
  that caution should always be exercised when
  working with animals you never know what they
  may be carrying.

99
Review Question

• Which animal is the reservoir for the Ebola Virus?

100
Answer

• The natural reservoir is not known

101
True or False

• Because all types of Ebola are limited to
  continental Africa, lab animal workers have no
  reason to worry about coming in contact with it
  in the United States.

102
Answer

• False the Reston subtype, though not yet known
  to be harmful to humans, has been found in the
  U.S.
• Additionally, African rodents may also be a
  reservoir and enter the US through the pet trade.
  This practice was stopped recently after the
  monkey pox outbreak caused by Gambian giant rats
  and dormice.

103
Marburg Virus Hemorrhagic Fever
Negative stain image of an isolate of Marburg
virus

• What is it?
• Marburg hemorrhagic fever is a rare, severe type
  of hemorrhagic fever which affects both humans
  and non-human primates, and is often fatal.
  Caused by a genetically unique zoonotic RNA virus
  of the filovirus family, its recognition led to
  the creation of this virus family. The four
  species of Ebola virus are the only other known
  members of the filovirus family. (9)

104
What is it?

• Marburg virus was first recognized in 1967, when
  outbreaks of hemorrhagic fever occurred
  simultaneously in laboratories in Marburg and
  Frankfurt, Germany and in Belgrade, Yugoslavia
  (now Serbia). (9)

105
What is it?

• A total of 32 people became ill they included
  laboratory workers as well as several medical
  personnel and family members who had cared for
  them. The first people infected had been exposed
  to African green monkeys or their tissues. In
  Marburg, the monkeys had been imported for
  research and to prepare polio vaccine. (9)

106
Where is it now?

• Recent occurrences have been limited to countries
  in sub-Saharan Africa.
• The current outbreak in Angola is the first
  report of Marburg virus disease since 1998-2000,
  when the then largest known outbreak, (154 cases,
  resulting in 128 deaths) occurred in the
  Democratic Republic of Congo. (9)

107
Outbreaks of Marburg HF.
As of 23 August 2005, the Ministry of Health in
Angola reported a total of 374 cases, including
329 deaths (CFR 88) reported countrywide. Last
confirmed case of Marburg died on 21 July 2005 in
Songo municipality, Uige Province. There have
been no laboratory confirmed cases since
then.(10) Update on this outbreak ?
108
How is it contracted?

• Just how the animal host first transmits Marburg
  virus to humans is unknown.
• Humans who become ill with Marburg hemorrhagic
  fever may spread the virus to other people.
• Persons who have handled infected monkeys and
  have come in direct contact with their fluids or
  cell cultures, have become infected. (9)

109
How is it contracted?

• Spread of the virus between humans has occurred
  in a setting of close contact, often in a
  hospital.
• Droplets of body fluids, or direct contact with
  persons, equipment, or other objects contaminated
  with infectious blood or tissues are all highly
  suspect as sources of disease.(9)

110
What are the symptoms?

• After an incubation period of 5-10 days, the
  onset of the disease is sudden and is marked by
  fever, chills, headache, and myalgia.
• Around the fifth day after the onset of
  symptoms, a maculopapular rash, most prominent on
  the trunk (chest, back, stomach), may occur. (9)

111
What are the symptoms?

• Nausea, vomiting, chest pain, a sore throat,
  abdominal pain, and diarrhea then may appear.
• Symptoms become increasingly severe and may
  include jaundice, inflammation of the pancreas,
  severe weight loss, delirium, shock, liver
  failure, and multi-organ dysfunction.(9)

112
What are the symptoms?

• Because many of the signs and symptoms of Marburg
  hemorrhagic fever are similar to those of other
  infectious diseases, such as malaria or typhoid
  fever, diagnosis of the disease can be difficult,
  especially if only a single case is involved.(9)

113
Precautions/Prevention

• Due to our limited knowledge of the disease,
  preventive measures against transmission from the
  original animal host have not yet been
  established. (9)

114
Precautions/Prevention

• Measures for prevention of secondary transmission
  are similar to those used for other hemorrhagic
  (Ebola) fevers
• Wearing of protective gowns, gloves, and masks
• Placing the infected individual in strict
  isolation
• Sterilization or proper disposal of needles,
  equipment, and patient excretions.(9)

115
Precautions/Prevention

• Viruses causing hemorrhagic fever exist in many
  places around the world, and modern travel
  patterns raise the possibility of importing an
  infectious disease to the United States or to
  other countries where the disease has not been
  previously reported.
• However, if Marburg virus infection were to reach
  the United States, health officials here have the
  ability to effectively isolate infected
  individuals and stop the spread of disease.(11)

116
Review Questions True or False

• Marburg Hemorrhagic Fever symptoms are very
  unique, which is why it is so easy to identify
  when it appears.

117
Answer

• False the symptoms are non-specific, making it
  difficult to identify.

118
True or False

• As with most other MHF outbreaks, the recent
  Angolan outbreak case fatality rate was well
  below fifty percent.

119
Answer

• False The most recent outbreak had a case
  fatality rate of 88. Most previous outbreaks
  were also above 50.

120
Hepatitis A

• What is it?
• Hepatitis A is a liver disease caused by the
  hepatitis A virus.

121
How is it transmitted?

• Humans are the primary reservoir for Hepatitis A
  virus.
• Non-human primate infections result from contact
  with infected humans.
• More than 200 cases of Hepatitis A virus
  infection in humans have been associated with
  nonhuman primates. (2)

122
How is it transmitted?

• Many nonhuman primate species are susceptible
• Chimpanzees and other great apes
• marmosets
• owl mokeys
• cynomolgus monkeys
• patas monkeys (2)

123
Chimpanzee
Owl Monkey
Patas Monkey
124
How is it transmitted?

• Hepatitis A virus is transmitted via the
  fecal-oral route, and some outbreaks can be
  related to contaminated feed and water.(2)

125
Symptoms - NHP

• The disease in NHP is much less severe than in
  humans and is often subclinical.
• Some species of NHP develop
• malaise
• vomiting
• jaundice
• increased serum concentrations of hepatic
  enzymes. (2)

126
Symptoms - Humans

• Varies from mild illness lasting 1-2 weeks to a
  severely debilitating illness lasting several
  months. After an incubation period of about a
  month, patients experience an abrupt onset of
• fever
• malaise
• anorexia
• nausea
• abdominal discomfort followed in a few days by
  jaundice (2)

127
Precautions/Prevention

• As with any other zoonotic disease, the use
  protective clothing, good personal hygiene, and
  appropriate practices of sanitation of equipment
  and facilities are essential. (2)

128
Hepatitis B,C,D,E

• As with Hepatitis A, humans are the natural host
  for Hepatitis B,C,D,E.
• Various NHP, particularly chimpanzees, can be
  infected experimentally, but only one case of
  natural infection has been reported.(2)

129
Hepatitis B,C,D,E

• Although natural infections of NHP with Hepatitis
  B,C,D,E viruses are extremely rare, personnel
  should adhere to appropriate precautions when
  handling NHPs.
• Hepatitis B vaccines are available and highly
  recommended for personnel involved with hepatitis
  B virus.(2)
• Many counties in North Carolina offer Hepatitis B
  vaccinations to middle schoolers.

130
Review Questions

• How is Hepatitis A transmitted?

131
Answer

• Fecal-oral route

132
Question True or False

• In NHPs, hepatitis A is much more serious with
  obvious clinical signs.

133
Answer

• False - The disease in NHPs is much less severe
  than in humans and is often subclinical.

134
In Closing

• Education and understanding are essential
• Wearing appropriate PPE and exercising caution
  when working with animals, whether it be rodents
  or NHPs, whether it be in Africa or in the US, is
  of utmost importance a new outbreak is always a
  possibility.
• Good personal hygiene is essential for disease
  prevention

135
References

• 1. Cohen, Davenport, Stewart, Deithcman,
  Hilliard, Chapman, and the B Virus Working Group.
  Reccomendations for Prevention of and Therapy
  for Exposure to B Virus. Clinical Infectious
  Diseases. 2002351191-203
• 2. National Research Council. Occupational
  Health and Safety in the Care and Use of Research
  Animals. Page 67. 1997.
• 3. CDC. Guidleines for Prevention of
  Herpesvirus Simiae (B virus) Infection in Monkey
  Handlers. Morbidity and Mortality Weekly Report.
  October 23, 1987.
• 4. NIOSH. Cercopithecine herpesvirus 1 (B
  Virus) Infection Resulting from Ocular Exposure.
  1999.
• 5. AALAS. ALAT Training Manual. 2001.
• 6. CDC. Shigellosis. http//www.cdc.gov/ncidod/d
  bmd/diseaseinfo/shigellosis_g.htm
• 7. CDC. Ebola Hemorrhagic Fever.
  http//www.cdc.gov/ncidod/dvrd/spb/mnpages/dispage
  s/ebola.htm
• 8. World Health Organization. Ebola
  Haemorrhagic Fever in the Republic of the Congo
  Update 2.
• http//www.who.int/csr/don/2005_06_16/en/index.htm
  l
• 9. CDC. Questions and Answers about Marburg
  Hemorrhagic Fever. http//www.cdc.gov/ncidod/dvrd/
  spb/mnpages/dispages/marburg/qa.htm
• 10. World Health Organization. Marburg
  Haemorrhagic fever in Angola Update 25.
  http//www.who.int/csr/don/2005_08_24/en/index.htm
  l
• 11. CDC. CDC Assists in Public Health Response
  to Marburg Hemorrhagic Fever Outbreak in Angola.
  May, 24, 2005. http//www.cdc.gov/ncidod/dvrd/spb/
  mnpages/dispages/marburg/cdcrole.htm

136
Disclaimer

• This presentation was completed while I was
  employed by Priority One Services (POS) at the
  National Institute of Environmental Health
  Sciences. Thus, both organizations deserve
  credit for supporting the work.
• However, the views expressed in this presentation
  are mine, and do not necessarily reflect those of
  POS, NIEHS, or UNC DlAM.