M20: Disease Transmission III: Zoonoses

Question 1

Zoonotic Infection:

• Zoonotic Infectious Diseases are transmitted from _ to _
• Reservoir = _
• Vector = generally refers to the _
• Xenozoonosis = A term in infectious diseases referring to _

Answer 1

animals to humans

animal where etiologic agent resides

medium (insect or other) transferring the etiologic agent between the animal reservoir and the human host.

transmission of infectious diseases from animal tissue transplantation.

Question 2

Factors Influencing Zoonoses

• Host:

• _ (travel, displacement, homelessness, occupational)
• new _ (finding more)

• Pathogen:

• transfer of _ or _
• expanded _, e.g. global warming

Answer 2

exposure
diagnostics

vector or reservoir
vector range

Question 3

Patterns of Zoonotic Infection

• Modes of Entry: (5)
• Humans are typically ‘_’, accidental intruders in an _ chain and _ (e.g., Lyme disease, Rocky Mountain Spotted Fever, Hantavirus, Rabies virus, anthrax).
• Humans acquire the infectious agent from _ and can pass it to other _ and/or _ directly or by _ (e.g. plague, influenza).

Answer 3

direct through skin, bite of animal, inhalation, ingestion, vector

dead-end hosts
animal-to-animal
cannot transmit the agent further

animals
humans ‘human-to-human transmission’
animals
animal or insect vectors

Question 4

Characteristics of Zoonotic Diseases

• Control is often difficult due to existence of a _.
• Often transmitted via (3); all efficient strategies for breaching the protective barriers of the host.
• Usually cause relatively (benign / malignant), (high / low)-grade infection in animal reservoir and are easily _ in this population.

Answer 4

mobile animal reservoir

ingestion, animal bites, or arthropod vectors

benign
low
spread

Question 5

Control of Zoonosis

Must use a multidisciplinary, common sense approach depending on the disease/vector/animal reservoir.

Approaches include: (5)

Answer 5

• Veterinary medicine
• Sanitary engineering
• Entomologic management
• Wildlife management
• Behavioral changes (humans)

Question 6

Hantavirus:

Biological Characteristics

• Hantaviruses comprise one of the five genera of the family, _.
• Spherical virus particles possessing a _ containing three distinct RNA molecules, each having (positive / negative) polarity. Bound to each of the virion RNAs are a viral-specific _ and multiple copies of a viral-encoded _.
• The envelope of the virus particle is derived from _ (buds from the _) and is associated with two virally derived _.

Answer 6

Bunyaviruses

nucleocapsid
negative
transcriptase
RNA-binding protein

intracytoplasmic membranes
Golgi
envelope glycoproteins

Question 7

Hantavirus:

Reservoir and Transmission

• Persistently infect a variety of _ species, often causing _ infections. Most commonly associated with _.
• Infectious virus found in (3) of infected rodents.
• Transmission occurs by _.

Virulence Factors

• The two _ determine the host range of hantavirions.
• Capacity to aggressively _ in the infected host, to be _, and to _ contributes to the pathogenesis of these viruses.

Answer 7

rodent
inapparent
deer mouse

urine, saliva and the feces

breathing in aerosols containing infectious material

envelope glycoproteins

multiply
excreted
survive dehydration

Question 8

Hantavirus:

Pathogenesis

• Most infected humans experience a(n) (symptomatic / asymptomatic) infection with (short / long)-lasting immunity.
• Three distinct disease may arise from infection by different hantavirus strains: (3)
• The virus appears to invade the animal or human being via the _ route where it replicates and then spreads via the _ to other organs, including the (5).

Initial symptoms include _ and any or all of the following:

• (7)
• _ disease complicated by _ shutdown adds to the severity of the disease and further complicates the maintenance of blood volume and electrolyte balance.
• HPS patient will often present with mild (3).

Answer 8

asymptomatic
long

• Hemorrhagic Fever (HF)
• Hemorrhagic Fever with Renal Syndrome (HFRS)
• Hantavirus Pulmonary Syndrome (HPS)

respiratory
blood
heart, gut, liver, kidney and central nervous system

fever

headache, malaise, myalgia and gastrointestinal distress, including vomiting, diarrhea, and/or cramping.

Hemorrhagic
renal

neutrophilic leukocytosis, hemoconcentration, and thrombocytopenia

Question 9

Hantavirus:

Diagnosis

• Made on clinical history, particularly with history of exposure to areas where _ reservoir may live, and symptoms confirmed by demonstration of _ by _ or by _.

Treatment and Prevention

• Treatment requires careful administration of intravenous transfusions of _, including _, and implementing _ if renal failure occurs.
• Prevention involves _ at risk populations to avoid vacant shelters and areas in which rodent infestation is apparent or likely.

Answer 9

rodent
viral RNA
reverse transcriptase–PCR or by serologic testing

fluid
electrolytes
kidney dialysis

educating

Question 10

Rabies virus:

Biological Characteristics

• Rabies virus is the most medically important member of the _ family that possesses one ((ss/ds)(DNA/RNA) molecule as their genome, enclosed within a _ capsid.
• Nucleocapsid is enclosed in an envelope containing trimers of a single viral _.
• RNA genome has a (positive / negative) polarity and covalently attached to an (DNA/RNA)-dependent (DNA/RNA) transcriptase that transcribes the genome into the five mRNAs encoding the sum total of the viral proteins.
• (Small / Large), _ virions

Answer 10

Rhabdovirus
ssRNA
helical

glycoprotein

negative
RNA
RNA

Large
bullet shaped

Question 11

Rabies virus:

Reservoir and Transmission

• (Symptomatic / Asymptomatic) infection of a broad range of mammalian hosts.
• In U.S. rabies is rare (fewer than 10 cases reported annually); much higher in other countries (estimated 55,000 people die of rabies each year in developing countries).
• _ animals: _
• In North America rabies is maintained in (4).

Virulence Factors

• Neuronal tropism in diverse _ species.
• Viral receptors include the (3)
• Asymptomatic persistence in selected vertebrate hosts allows for _.

Answer 11

Asymptomatic

Domestic animals: dogs, cats, and other pets

skunks, raccoons, foxes and bats

vertebrate

acetylcholine receptor, neural cell adhesion molecule, and a neural ganglioside.

maintenance of virus

Question 12

Rabies virus:

Pathogenesis

• Animal bite allows rabies virus access to _ cells where it spreads to _ cells and moves by axonal transport to the _. Incubation period can last up to 12 months.
• In the CNS the virus migrates down the peripheral nerves to other organs, in particular the _, where it is poised to be transmitted through a _.
• Clinical illness may begin with _ at the bite site.
• Secondary symptoms are followed by (4). Behavioral changes, including irrational aggressive actions, often ensues.
• A characteristic symptom of advanced rabies is _. Within several days, (3) ensue. Death results from (4).
• In most vertebrates invariably fatal _ develops with neuronal death and demyelination of the neuronal sheath.

Answer 12

muscle
peripheral nerve
CNS

salivary glands
bite

abnormal sensation

confusion, lethargy, paresis, and increased salivation

hydrophobia, an aversion to swallowing water because of painful spasms of the throat and neck

seizures, paralysis, and coma
cardiac and respiratory failure, encephalitis, autonomic dysfunction, and vasospasm

encephalitis

Question 13

Rabies virus:

Diagnosis

• Clinical history of contact with _ is the most important reason to suspect rabies exposure.

Prevention and Treatment

• There is no _ therapy for rabies. Once clinical signs appear, the disease is almost always _. There is one well-documented case of a rabies survivor without immunization and PEP.
• Pre-exposure immunization using _ virus derived from _ is recommended for individuals at high risk.
• Post-exposure rabies prophylaxis (PEP) involves the immediate _ of the wound (soapy water and alcohol) and the injection of _. At the same time, the patient is begun on a series of 4 injections of _. Recommended regimen will differ depending on the vaccination status of the individual.

Answer 13

rabid animals

antiviral
fatal

inactivated
human diploid cells (HDCV)

cleansing
human rabies immune globulin (HRIG)
HDCV vaccine

Question 14

Rickettsia rickettsii:

Biological Characteristics

• The Rickettsiaceae comprise a family of atypical bacteria grouped on the basis of clinical features associated with disease, epidemiological characteristics, and morphologic properties.
• (Obligate / Facultative) (intracellular / extracellular) pathogens
• Characteristically (smaller / larger) than typical bacteria (600 x 300 nm).
• Too small to _ but have a gram-(positive / negative) ultrastructure.

Answer 14

Obligate
intracellular

smaller

gram stain
negative

Question 15

Rickettsia rickettsii:

Reservoir and Transmission

• Transmitted to humans by way of _ vectors–geographically restricting the disease to the distribution of them. _ caused by Rickettsia rickettsiae is the most common disease.
• _ is among the most severe human infectious diseases, with a mortality rate, when untreated, of 25%. With treatment, the case fatality rate is 4%.
• The term “Rocky Mountain Spotted Fever” is misleading because this disease is distributed throughout _ and _.
• _ of the _ species harbor R. rickettsii. This organism is maintained within the environment principally by _ transmission from infected female ticks to offspring. Less commonly, uninfected ticks become infected after feeding on small mammals experiencing a rickettsitemia.
• Transmission to humans is accomplished by a _. Children who have pets or who explore wooded areas are particularly vulnerable to tick exposure.

Answer 15

arthropod
Rocky Mountain Spotted fever

Rocky Mountain Spotted fever

North and South America

Ticks
Dermacentor
transovarial

tick bite

Question 16

Rickettsia rickettsii:

Virulence Factors

• Ability to direct _ within infected cells resulting in the formation of cell projections (_) that may enhance spread between cells that comprise _ linings.
• (3) result in host cell damage.
• “_“—Rickettsiae exchange _ for the higher energy form of _ from the intracellular pool.

Answer 16

actin reorganization
filopodia
vascular

Phospholipases, proteases, and membrane peroxidation

Energy parasites
adenosine diphosphate (ADP)
adenosine triphosphate (ATP)

Question 17

Rickettsia rickettsii:

Pathogenesis

• Post-bite the incubation period ranges from two to 12 days.
• Disease begins abruptly with (5).

(8) may follow.

A _ develops between two and four days after onset of symptoms and is generally localized to the extremities. Rickettsiae readily invade many mammalian cells yet are mainly seen in the _ endothelium (_). It is thought that lysis of thesecells leads to rupture of capillaries and small vessels.

Answer 17

fever, malaise, severe frontal headache, myalgia and vomiting

Abdominal pain, diarrhea, conjunctivitis, mental confusion, meningitis, respiratory difficulties, renal dysfunction, and/or myocarditis

rash
vascular
endothelitis

Question 18

Rickettsia rickettsii:

Diagnosis

• Diagnosis of Rocky Mountain spotted fever is typically based on the clinical signs and exposure history.
• Difficult to _ and are extremely _.
• Commonly used tests include _ of patient specimens with _ and/or _.
• _ test uses antigens derived from an unrelated organism _ in lieu of rickettsial antigens. Though this diagnostic test is relatively insensitive and non-specific, it does have the advantage of being inexpensive.

Prevention and Treatment

• _ is the most important means for its prevention
• Prompt treatment with _ is effective during the early stages of disease

Answer 18

culture
infectious

immunostaining
anti-rickettsial antibodies
ELISA

Weil-Felix
Proteus vulgaris

Public awareness

doxycycline

Question 19

Borrelia burgdorferi:

Biological Characteristics

• Borrelia spp. are members of a small class of medically important bacterial pathogens referred to as _.
• All spirochetes have an ultrastructure similar to gram (positive / negative) organisms.
• Spirochetes differ from gram-(positive / negative) bacteria by containing several _ structures within the _ (), typically extending from the surface of bacteria. This gives rise to the characteristic “” appearance of the spirochete.
• Spirochetes are so thin (0.1 to 0.2 µm) they cannot be seen by standard light microscopic techniques such as those employed in the gram stain procedure. Instead special stains (_ or ) or special lighting conditions () must be used to visualize these organisms.

Answer 19

spirochetes

negative

negative
flagellar 
periplasm 
endoflagella
corkscrew

silver impregnation or immunofluorescence
dark field microscopy

Question 20

Borrelia burgdorferi:

Reservoir and Transmission

• B. burgdorferi is the etiologic agent of _, or _.
• In the United States ~30,000 confirmed and probable cases of Lyme disease were reported to CDC in 2010, underscoring its significance as a frequent _ infection.
• Reservoir is in _.
• Lyme disease is transmitted by a _ vector, typically a member of the genus _.
• Three major endemic foci:
• the coastal wooded regions of southern _
• the _ states; areas of (3)
• the coastal and wooded areas of _ and _

Answer 20

Lyme disease
Lyme borreliosis

zoonotic

rodents

tick
Ixodes

New England, New York
Middle Atlantic, Wisconsin, Michigan, and Minnesota
California and Oregon

Question 21

Borrelia burgdorferi:

Vector

• Ixodes ticks exhibit three seasonal stages in their life cycle; (3).
• _ and _ stages can transmit the disease to humans, _ less likely to be noticed.
• _ and _ feed on rodents, e.g. white-footed mouse, resulting in high rates of infection.
• _ feed on deer, necessary to sustain the ticks.

Answer 21

larva, nymph and adult

Nymph and adult
nymphs

Larva and nymph

Adults

Question 22

Borrelia burgdorferi:

Virulence Factors

• B. burgdorferi expresses important surface lipoproteins, referred to as _ — many of which demonstrate antigenic variability.
• These surface proteins are differentially expressed depending on whether the organism is growing in the _ or the _.
• Osps are thought to be important for _ and for the activation of _ in the tick or the human.
• _ have been associated with Osp expression by B. burgdorferi
• The type of Osp expressed may influence the _ or _, underscoring the importance of attachment in microbial pathogenesis.

Answer 22

Osps (outer surface proteins)

tick
human

tissue attachment (adhesins)
B. burgdorferi growth

Plasmids

reservoir or tissue tropism

Question 23

Borrelia burgdorferi:

Pathogenesis

• Lyme disease follows three stages.

• Early (2-30 days). Patient may be _. Tick bite may not be noticed yet _ begins at bite locus within a few days to a month; typically 15 cm in diameter; _. 50% children and 30% adults will not exhibit a rash. General symptoms: (6) lasting for several weeks.
• Early-Disseminated (2wks- 6 mos). Ten percent of patients experience (3) (disease of spinal nerve roots and nerves). _ and _ may be seen in rare cases and patients experience transient _.
• Late (2 mos-7 yrs). _ (large joints) in 60% patients intermittent _ may occur for 3-7 years (10% untreated cases with chronic arthritis), chronic _ syndromes, including multiple ECM lesions, are common and _ with dysfunction ranging from fatigue to dementia.

Answer 23

asymptomatic
ECM
bright red expanding edge central area of clearing (bull’s eye)
malaise, fatigue, headache, fever, chills and myalgia

cranial neuropathy, meningitis, and radiculoneuropathy
Iritis and necrotizing retinitis
cardiac dysfunction (AV-block)

Oligoarthritis
arthritis
dermatologic
neurologic demyelination

Question 24

Borrelia burgdorferi:

Pathogenesis

• Nymphal and adult tick forms infected after feeding on a B. burgdorferi-infected reservoir pass the organism to humans during a _ by _ into the _
• Transfer of the _ from infected _ to _ requires a period > 48 h.
• B. burgdorferi is thought to attach to a _ receptor on cells at the site of the tick bite where it grows.

Answer 24

blood meal
salivation of spirochetes
bite wound

spirochetes
ticks to humans

proteoglycan

Question 25

Borrelia burgdorferi:

Diagnosis

• B. burgdorferi is easier to culture from _ but difficult to grow from clinical specimens such as (3)
• Diagnosis is typically made on case history, clinical symptoms, and confirmed serologically.
• Early serologic tests for Lyme disease had several limitations, including lack of _, _, and the time required for an individual to _.
• A standardized _ approach is recommended for the diagnosis of active and previous Lyme disease.
• The first step uses a sensitive _ or _, each made more specific by the inclusion of _ antigens that do not cross-react with other microorganisms. Specimens negative by these tests need not be tested further.
• The second step is to confirm a positive test using a standardized _ procedure

(Even with the Two-tiered approach there is still a problem of early diagnosis)

Answer 25

edge of the ECM
blood, CSF, or synovial fluid

laboratory-to-laboratory standardization
cross-reactivity
seroconvert

two-tiered

enzyme immunoassay (EIA) 
immunofluorescent assay (IFA)
flagellar 

Western immunoblot

Question 26

Borrelia burgdorferi:

Prevention and Treatment

• _ modifications to residential properties (e.g., application of insecticides, use of deer fencing, and removal of leaf litter) may help prevent the transmission of Lyme disease to humans.
• _ methods recommended for the prevention of all forms of tick borne diseases are also important.
• Such measures include wearing _ colored clothing (to more readily detect ticks), tucking long pants into _, and using _ and _.
• Performing _ checks daily is perhaps the most important means of prevention since removal of the tick within _ day(s) of exposure can interrupt disease transmission.
• The high incidence of the Lyme disease within the United States makes the development of a vaccine a priority. _ vaccine (antigen used was _) is no longer available. No vaccine is currently available in the U.S.

Answer 26

Environmental

Personal protection

light
socks
insect repellents and acaricides

tick
one

LYMErix
OspA

Question 27

Borrelia burgdorferi:

Prevention and Treatment

• Lyme disease cases can be managed with antibiotic therapy.

Ø Early stages

• Erythema migrans: _, _, or _ orally for 14 days
• Meningitis or carditis: Intravenous _ at 2 grams once daily, for 14 days (though some successful use of oral _)

Ø Late stages

• Lyme arthritis: _, _, or _ orally for 28 days
• Central nervous system: Intravenous _ for 14-28 days

Answer 27

Doxycycline, amoxicillin, or cefuroxime

ceftriaxone
doxycycline

Doxycycline, amoxicillin, or cefuroxime

ceftriaxone