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1

**What are the three criteria that define a Zoonotic Infectious Disease? **

1. a vertebrate reservoir exclusive of humans
2. transmission of the agent directly to people or from products derived from host animal or through an arthropod intermediate
3. a recognized infectious disease syndrome in susceptible individuals

2

What increases the occurrence of zoonotic diseases?

-as animals become domesticated and close bonds developed between animals and humans

3

**Define
Enzootic
Epizootic**

Enzootic: refers to a disease that is endemic (i.e. present at stable levels) among animal populations
Ex: Lyme disease in ticks and mice and plague in rats


Epizootic: and “epidemic” in animals
If in a specific locations, it an “outbreak”
If widespread it is “panzootic”

4

Define panzootic

Widespread epidemic in animals

5

Define:
Epidemic

Refers to human disease spread to a large number of people within a defined short amount of time

6

Types of zoonotic infections (5)

Bacterial
Viral
Fungal
Parasitic
Prions

7

**A majority of zoonotic infections are: **

Viral

8

What two things have increased human activity into wilderness areas?

-Tourism
-Deforestation

9

What is one prominent route of transmission?

Fecal-oral route:
-not always obvious
-pathogens may survive for long periods of time in the environment

10

What diseases can be passed through direct contact?

- Ringworm
- Scabies
- Ear mites
- Hookworm larvae

11

What diseases can be passed through insect vectors?

Mosquitoes - heartworms and encephalitis
Heartworm in humans extremely rare, but few reports can be found

Fleas - tapeworms, cat scratch fever, plague, typhus.

Ticks - Lyme disease and RMSF

12

List some agricultural exposures

1. Frequent contact with domestic animals
2. Overlap with wildlife habitat
3. Large scale livestock production
4. Poor animal sanitation and personal hygiene

13

What diseases are a result of agricultural exposure to live stock?

-E. Coli
-Q-fever
-Giardia
-Salmonellosis
-Rabies
-Ringworm

14

**T/F**

Salmonella is a part of the normal gut flora in turtles and is shed in their stool, heavily contaminating whatever environment they are in

True

15

**What happened after turtle/aslmonella outbreak **

Small turtles (<10cm) were banned specifically to protect children as these are often purchased for children

Federal ban is difficult to enforce, many locally owned or independent pet shops still sell small turtles

16

**T/F **

Rabies has been used as an attempted weapon

True

Some attempted to use it as a weapon
DaVinci : terror-bomb created from Sulphur, arsenic, tarantula venom, toxic toads, and the saliva of mad dogs

17

T/F

Rabies remains endemic throughout the world

True

2/3 of the world’s population lives in a rabies endemic area

18

T/F

Rabies virus has the ability to infect and replicate in a wide host range

True

19

T/F

Rabies deaths are predominately in the developing world

True

50,000/year
Main reservoir associated deaths are canines

20

Rabid dog exposures to rabies is responsible for

>_____% of human exposures
>______% of human deaths

>90% of human exposures
>99% of human deaths

21

Rabies order:
Two members of this order:

-Mononegavirales order
-members: filoviridae (ebola) and paramyxoviridae (measles)

22

Rabies Order:
Family:
Genus:

-Order: Mononegavirales
-Family: Rhabdoviridae
-Genus: Lyssavirus

23

Rabies has a ________________ genome

Non-segmented negative strand genome

24

Rabies virions are ______ shaped with ______ appearance

“bullet” shaped, with “spiky” appearance

25

Currently, where do a majority of Rabies cases occur in the United States?

90% occur in wildlife

26

**Majority of rabies cases occurring in which areas?**

Asia & Africa

27

**Rabies has never been endemic in: **

New Zealand & Australia

28

Two types of spread/maintenance of Rabies:

1. urban: through dogs
2. sylvactic: through wildlife

29

What is the main reservoir for rabies worldwide? And why?

Main reservoir worldwide is dogs
Main reason for spread is lack of rabies control programs and lack of vaccinations

30

What is the main reservoir for rabies in the US? And why?

Main reservoirs in US are wildlife, due to successful dog vaccination programs

31

In the US which wild animal accounted for most of the rabies cases?

1. Bats
2. Raccoons
3. Skunks
4. Foxes

32

In the US which domestic animal accounted for most of the rabies cases?

Cats`

33

**In order which were the most highly reported of rabies from wildlife species?**

1. Bats
2. Racoons
3. Skunks
4. Foxes

34

Rabies in:
Europe

Successful control but fox and raccoon populations continue to pose a threat to complete elimination

35

Rabies in:
Asia

Grossly underreported

In India alone, estimated 20,000 people die of canine rabies.
Dramatic rise of rabies in China.

36

Rabies in:
Africa

Primarily canine in origin
Jackals, bat-eared foxes and mongoose are involved in rabies transmission in Africa

37

Rabies in:
Central & South America

Thru PAHO rabies vaccine programs, over the past 20 years has led to an almost 90% decrease in dog and human cases.

38

**Rabies disease transmission**

1. Bite of an infected animal that contains virus in the saliva (Infection may occur at exposed mucous membranes (conjunctiva, oral mucosa….)

2. Inhalation of aerosolized virus in bat caves has been reported. (extremely rare)

3. Organ transplantation has been reported

4. After the bite, the virions may enter the CNS directly or after initial replication within muscle tissue
Enters motor nerves through neuromuscular junctions
Can stay at inoculation site for days to months

39

T/F

Non-Bite Exposure of rabies is common

False

- Aerosol exposure: laboratory accidents, caves with high concentrations of bats
Open wounds or mucus membranes must come into contact with infectious material like saliva or brain tissue

- Organ transplant

40

What is the incubation phase?

When the virus remains at inoculation site for weeks to months before ascending up nervous system.
-patient is asymptomatic
-length of phase determined by amount of virus and how close bite was to CNS

41

What is the prodrome phase?

When the virus starts to ascend

42

What is the neurologic phase?

When the virus infects the brain; infection is rapid and spreads to tissues
-classic finding histologically is through Negri Body

43

Steps of prodrome phase:

1. Enters peripheral nervous system (nerves not in the brain or spine)
2. Ascends up via sensory fibers
3. Replicates in Dorsal Root Ganglia
4. Rapidly ascends into spinal cord

44

Aspects of incubation phase:

1. Virus inoculated through bite
2. Replicates locally in muscle near bite

45

Steps of neurologic phase:

the infection of the brain is rapid as is the spread to the tissues

1. Infects CNS (spinal cord, brainstem, cerebellum, other parts of brain)
2. Infection descends into eye, salivary glands, and skin

46

**T/F**

Rabies infection elicits an antibody response early before the beginning of the neurologic stages of the disease

False

Rabies infection does not elicit an antibody response until the late neurologic stages of the disease

However, antibody is effective at stopping the disease prior to the neurologic phase

47

**What 5 factors determine length of incubation period?**

1. The concentration of the virus in the inoculum
2. The proximity of the wound to the brain
3. Severity of the wound
4. Host’s age
5. Host’s immune status

48

Describe how the virus travels after the bite:

Virus replicates in the neuromuscular junction in the muscle tissue --> travels up the motor nerve --> replicates in the spinal cord --> travels and infects brain --> infects salivary gland to produce infectious saliva --> passes on to next animal or person

49

Incubation period for rabies is typically ______ days but may be as long as _____ years

20-90 days
14-19 years

50

**Entry virus at a _______ innervated site often leads to swift progression (ex: hands vs calves)**

highly

(Also factors, the dose delivered, the subtype of rabies virus, and types of nervous tissue at bite site, depth of the bite, closer to the head)

51

Mortality rates for rabies due to location/type/extent of wound highest to lowest

1. Face/bite/deep (60%)
2. Face/nite/single
3. Fingers/bite/severe
4. Trunk+legs/scratch/mutiple
5. Skin covered by clothes/wound/superficial (0.5%)

52

5 clinical stages of rabies

1. Incubation Period
2. Prodrome PHase
3. Acute Neurologic PHase
4. Coma
5. Death

53

Describe approximate time for each of the clinical stages:

1. Incubation Period (5 days to 2 years)
2. Prodrome PHase (0-10 days)
3. Acute neurologic phase (2-7 days)
4. Coma (5-14 days)
5. Death

54

Prodrome- Early symptoms may be difficult to appreciate
and may resemble

tetanus, typhoid, malaria, and other viral encephalitis

Fever, nausea, vomiting, headache, lethargy

55

Describe the ACUTE NEUROLOGICAL DISEASE of rabies

-80% develop “furious” rabies
1. Hyperactivity, disorientation, bizarre behavior, hypersalivation, sweating
2. Hydrophobia is actually dysphagia

- 20% develop paralytic rabies (“dumb”)
1. Ascending symmetric paralysis with flaccidity and decreased tendon reflexes

56

T/F

We have had an effective vaccine for rabies has been available for over 100 years

True

Invented by Pasteur in 1885
100% effective

57

**T/F**

Rabies vaccine may be given pre-exposure or post exposure

True

58

Who received pre-exposure rabies vaccine?

-those working with the virus or have potential of contact

59

What are the key factors for post-exposure vaccine?

*TIMING*
1. should be administered rapidly
2. expensive and in short supply
3. Rappid immunoglobulin should be injected surrounding wound and any left over injected into the intramuscular in addition to the vaccine

60

T/F

Animals can be vaccinated for rabies

True

Estimated that at least 50 million dogs are vaccinated each year against rabies.

However, in many parts of Asia and Africa the vaccination coverage established in the dog population (30% to 50%) is not high enough to break the transmission cycle of the disease

61

What are three considerations for rabies prophylaxis?

1. epidemiology of rabies in the region
2. type of exposure
3. whether it was provoked or unprovoked
4. species and vaccination status of animal

62

Data shows that animals like dogs, cats, and ferrets begin to sicken and die within _______ days of exposure to rabies

10 days

63

If a domestic animal with rabies bites a person, then they should be observed for ______ days

10 days

-If they show any illness, then they should be euthanized and the head should be shipped to a laboratory for rabies testing
- If animal is healthy for 10 days, then no rabies
- If bit around head, prophylaxis immediately as the incubation period can be as short as four days

64

Post-exposure prophylaxis consideraitons:

-after bite, wash area with soap and water and use virucides (providone-iodine)
-active and passive immunity (RIG + Vaccine)
-must be given asap

65

Who is encouraged to take rabies pre-exposure prophylaxis?

1. people working with or around potentially rabid animals 2. Children living in rabies-endemic areas
3. people in areas where dog rabies is common and who cannot be in a location where safe and effective biologics are reliably available within three days after exposure
4. animal workers, lab workers who handle potentially infected tissue, travelers

66

T/F

Fleas are wingless, bloodsucking insects

True

Have existed for at least 50 million years

67

T/F

Fleas have a wide range of hosts

True

More than 200 species of mammals

68

T/F

Fleas can cause dermatological problems and act as zoonotic vectors

True

Flea associated ID cases seem to be concentrated in coastal and more temperate zones that are ideal for rapid flea life cycles

69

Flea-associated ID cases seem to be concentrated in ___________ zones that are ideal for rapid flea life cycles

coastal and more temperate

70

**Which diseases are spread by the flea Xenopsylla cheopis? **

Agent: Y. Pestis; Disease: Plague
Agent: Rickettsia Typhi; Disease: Murine Spotted Fever

71

**What are the four main factors that promoted spread of plague?**

1. poor sanitation
2. illness
3. dirt
4. overcrowding

72

**Describe the mechanism for Bubonic Plague Spread by the flea**

1. Flea feeds on rats
2. Fleas feeding on infected host get midgut obstructions due to Y. pestis
3. These fleas begin to starve and become aggressive; attempt to feed on anything and regurgitate large quantities of bacteria into new host
4. When the rats not immune to the disease died, the fleas would sometimes feed on humans, creating accidental hosts and spreading plague

73

Yersinia Microbiology

-gram negative bipolar staining bacillus
-grows aerobically

74

**What are the three virulence factors for Yersinia?**

1. Plasminogen activator- bacterial surface protein important for survival in fleas, responsible for the bolus of blood ( see later slide)

2. Pesticin-promotes iron uptake for Y pestis

3. Lipopolysaccaride Endotoxin-promotes cytokine cascade

75

Plasminogen activator in yersinia does what?

bacterial surface protein important for survival in fleas, responsible for the bolus of blood

76

Pesticin in yersinia does what?

Promotes iron uptake for Y pestis

77

Lipopolysaccaride Endotoxin in Yersinia does what?

Promotes cytokine cascade

78

**Reservoirs for Yersinia**

- Primarily rodents (urban and domestic rats)
- Also squirrels, mice, and prairie dogs
- Less common cats, dogs, rabbits

79

**Transmission of Yersinia occurs via (2)**

- Flea bites (more commonly)

- Inhalation of infected respiratory specimens of infected humans or cats

80

Primary ways plague is transmitted in the US?

1. In Nature: primarily in southwestern states where Y. pestis is transmitted by fleas to rodents, squirrels, prairie dogs and rats
2. To Humans: humans and domestic animals are bitten by fleas from dead animals; cats can become very ill and infect humans through cough infectious droplets

81

**Blocked flea model of plague**

1. Flea feeds on bacteremic host
2. Y. pestis colonizes flea midgut, replicates, and creates a blockage of the flea intestine as seen in previous image
3. Flea starves and becomes aggressive
4. As flea rapidly feeds, it regurgitates into the wounds and infects subsequent hosts

82

Sylvatic Plague
Enzootic

- Plague maintained at steady level in rodent populations
- Low death rates
- Squirrels, Chipmunks, Mice, Rabbits affected

83

**Sylvatic Plague
Epizootic**

- Large die-offs, fleas change hosts
- Amplifying hosts: prairie dogs, ground squirrels, rock squirrels, woodrats, chipmunks (vectors that reach blood levels of the organism high enough to infect other fleas)
- Expansion into human occupied areas

84

**Urban Plague**

-Infected fleas or rodents move to urban area
-Increased number and areas of western U.S. cities: suburban-wilderness zone
- Commensal (domestic) rodents (Roof rat, Norway rat
....Rat fleas may feed on humans)
- Poverty, lack of sanitation, homelessness contribute

85

**Three Types of Clinical Plague**

Bubonic
Primary Septicemic
Pneumonic

86

**Bubonic Plague Symptoms**

- Incubation period of 1-7 days
- Sudden onset
(Fevers >38, malaise, myalgia, dizziness, painful lymphadenopathy near the site of the bite
Bubo = tender swollen lymph node with boggy consistency and hard core upon palpation
Exquisitely tender without fluctuance)

- If untreated, it can progress to septicemia

87

Primary Septicemic Plague clinical presentation

- Gram negative septicemia without plague symptoms/buboes
- Sepsis
-Patients appear extraordinarily ill and febrile without localizing symptoms
- Calculated using SOFA (Sequential Organ Failure Assessment) score paired with unstable vital signs

88

**Pneumonic Plague symptoms**

**only one with 100% mortality untreated**
1. Short incubation period after exposure, averaging a few hours to 3 days
2. Sudden onset of fever, and nonspecific signs such as headache, myalgia, and vomiting
3. Respiratory manifestations (Cough, chest pain, sputum production with hemoptysis)
4. Untreated has 100% mortality, treated has 50% mortality
5. Has been associated with sick domestic cats transmitting vial aerosol droplets to their owners
6. Only form of plague that can be transmitted from person to person

89

**Which plague has 100% mortality if untreated**

Pneumonic Plague

90

Which plague is associated with sick cats?

Pneumonic Plague

91

Pneumonic Plague clinical manifestations

1. Secondary complications

2. Pneumonic Plague- Infection reaches the lungs by hematogenous spread of bacteria from the bubo, Highly contagious, patchy infiltrates on x-ray, Sputum can be purulent with high counts of bacilli

3. Meningitis-A rare complication
(Occur more than 1 week after partially treated bubonic plague. Assoc. with disease high involvement)

92

How many cases of plague in the US do we get each year? Which type? Where? What time of year?

10-20

Bubonic plague = 85% of the cases
Most prevalent in “Four Corner” States
Typically in summer
The fleas live on prairie dogs, which live in the area and are social animals

93

Which plague is thought to have arisen from infective flea bites in the US?

Bubonic Plague

94

Which plague is associated with happening often after handling infected animal tissues in the US?

Primary Septicemic Plague

95

Which plague is associated with exposure to sick cats?

Primary pneumonic plague

96

Plague in California occurs where?

- Occurs in foothills, plateaus, mountains, and coasts
- Absent from southeastern desert and Central Valley

97

**Diagnosing Plague (4 things to look for)**

1. The symptoms are very non specific so it requires high clinical suspicion for modern diagnosis

2. The presence of fever in a person with either known contact with dead rodents or residence or travel to a plague-endemic region.

3. The presence of fever, hypotension, and unexplained regional lymphadenitis.

4. The presence of clinical findings of pneumonia in association with hemoptysis and sputum containing gram-negative rods on Gram stain.

98

Which tests are used to diagnose plague

1. Smear and culture of buboes aspirate or blood smears
- Look for the coccobacilli (1-2um in length)
- Wayson’s stain-appears as light blue bacilli with dark blue polar bodies
- Classic “safety pin” appearance
- Culture on blood or MacConkey media

2. Specific tests have been developed for the F1 antigen with 100% specificity and sensitivity

99

**What does Y. pestis look like under a microscope?**

Like small blue bacilli; safety pin structure

100

Untreated plague has a mortality rate of > ________

50%-100%

101

Untreated Pneumonic plague = _________-

100% mortality

102

Bubonic plague has a mortality rate of ______ percent if untreated ___________ if treated.

50 to 90% untreated
10 to 20% if treated

103

**Treatment of choice for plague**

Gentamicin

(Tetracycline or doxycycline are oral options)

104

Plague in Madagascar

- The most severely affected country in the world
- In 2015, there were 275 cases with 63 fatalities
- One significant outbreak started in 2014
- Currently undergoing an outbreak

105

**What is the flea species affecting Madagascar**

Xenosylla cheopis

106

_______ infesting black rats is the most common reservoir in Madagascar

Xenosylla cheopis

107

**Number of reasons for spread of plague in Madagascar
(5)**

1. Political instability (Coup in 2009 resulted in declining foreign aid and inability of local and national governments to work together)

2. Flooding (Flushed rats out into the open)

3, Infrastructure (Numerous slums in the capital city with no services, overcrowded prisons filled with rats)

4. Villagers tend to keep animals inside with them to prevent theft (Exposes to fleas)

5. Traditions (Bodies infected with plague should be buried immediately and sealed... Famadihana “the turning of the bones”)

108

**Famidihana in Madagascar**

Called “the turning of the bones”

1. Wisdom of ancestors is revered in Madagascar culture
2. Refers to a ritual where bodies are unearthed every 5-7 years to be rewrapped in silk
3. Given these factors, the bodies of plague victims are often unearthed by the family and snuck back to villages, exposing many to plague
4. Concrete graves have been made to discourage this

109

T/F

Plague is endemic on the Plateau of Madagascar, including Ankazobe District, where the current outbreak originated

True

- A seasonal upsurge, predominantly of the bubonic form, usually occurs yearly between September and April.

110

T/F: This last year plague season is affecting both endemic and non-endemic areas including major city centers and port cities?

True:

-plague season began earlier and current outbreak is affecting Antananrivo and Toamsina

111

Which countries are at risk for plague?

- Ethiopia
- Kenya
- Tanzania
- Madagascar
- Mozambiique
- South Africa
- Comoros
- Seychelles
- Mauritus
- Reunion

112

Where is the newest plague outbreak occurring?

Seychelles

113

**R. typhi is linked to ______ and _____**

rats and rat flea (Xenopsylla cheopis)

114

R. typhi recently been linked to ______in southern California and new vector cat flea

opossum

115

**R. typhi is caused by ________**

Caused by Rickettsia typhi
Referred as “endemic typhus” or “flea borne typhus”

116

Rickettsia typhi is a ________ gram _________________

Small gram negative obligate intracellular bacterium

117

How is typhus transmitted? And when do we see most cases?

- Disease is transmitted after the inoculation of infected flea feces into a pruritic flea bite wound
- Can also infect the reproductive organs of fleas, allowing for transmission of the bacterium to future flea population transovarially

- Cases occur year around with a peak during summer and early Fall

118

T/F

Rat flea does not routinely bite humans but will do so in the absence of their normal hosts

True

119

T/F

LA county accounts for 42-90% of cases of typhus in the state

True

120

**Clinical manifestation of typhus **

- Can mimic long list of infectious etiologies (Many clinicians do not suspect this disease)

- Bacteria infect endothelial cells lining vessel walls
(Causing vascular inflammation. Fatal cases are attributed to end organ failure due to vasculitis)

-. Clinical manifestations range from mild to fatal
Mild symptoms are non-specific, constitutional
Case fatality rate is 1% (with abx)-4% (w/o abx)

- Incubation period is 1-2 weeks before onset of illness

- Initial presentation is nonspecific

- Rash (macular, petechiae, usually on ches)

- Neurological (confusion, seizure, stupor, ataxia)

121

Treatment of typhus

- Doxycycline is usually first line, empiric treatment (There is a usually a rapid clinical response)
-many patients recover without any treatment

122

Prevention of typhus:

- Cornerstone of prevention is control of flea and mammalian reservoirs

- Foliage in the yard trimmed to reduce harboring rodents, opossums etc..

- Food sources should be contained to avoid attracting animals to residence

123

Tungiasis is caused by what?

Tunga penetrans

124

Tunga penetrans is distributed in __________ regions of the world

tropical and subtropical

including Mexico to South America (endemic), the West Indies and Africa (introduced)

125

Tungiasis fleas usually are where? Associated with what animals?

The fleas normally occur in sandy climates, including beaches, stables and farms

Associated strongly with stray dogs > cats

126

Tungiasis prevention

(1) insecticide treatment of flea-infested domestic and stray animals and pets with 10% pyrethrin or pyrethroid sprays or 1% to 4% malathion powder

(2) bathing the feet of domestic and stray dogs and pigs with insecticide solutions, such as 2% trichlorfon

(3) spraying or dusting households, especially those with dirt floors, with 1% to 4% malathion

127

Tungiasis treatment

Extracting all embedded fleas immediately with sterile needles or curets

- Treat secondary bacterial infections
- Administer tetanus prophylaxis (Tungiasis has been associated with lethal tetanus in nonvaccinated individuals and was identified as the place of entry for 10% of tetanus cases in São Paulo in a 1991 study)

128

**T/F: Brucella is the most common zoonotic disease in the world**

True

-500,000 new cases annually

-Increasing prevalence w/ rise in tourism

129

**How is Brucella transmitted to humans?**

-Direct contact with fluid from infected animals

-Consumption-can be passed by food products (i.e. unpasteurized milk and cheese)

-Inhalation

-Aerosol

130

Identify the 6 Brucella species and the most commonly associated reservoir

1. B.melitensis (small ruminant-goats and sheep)

2. B. abortus (cattle)

3. B. suis (swine)

4. B. canis (dogs)

5. B. neotomae (desert wood rats)- not pathogenic to humans

6. B. ovis (sheep) -not pathogenic to humans

131

**T/F: All six Brucella species cause disease in humans.**

False

Only four are pathogenic to humans (melitensis, abortus, suis, and canis)

132

**Which two forms of Brucella are most virulent to humans?**

B. Melitensis and B. suis

133

What are the microbiology characteristics of Brucella (morphology, gram negative/positive, etc)?

-Gram negative coccobacilli (rods)

-No spores, capsules or flagella

-Facultative intracellular aerobe

134

How does pasteurization prevent brucellosis?

-eliminates the organism

-reduces number of human cases

135

Majority of worldwide cases of Brucella are attributed to B. _____________

Melitensis

136

What occupations are at an increased risk for Brucellosis?

-Shepard’s

-veterinarians

-dairy-industry professionals

-micro lab personnel

137

**How might a Brucella infection cause spontaneous abortions in cattle?**

-Brucella has an affinity for tissues rich in erythritol (i.e animal uterus, breast, and placenta)

-the organism will multiply in the uterus

138

Brucella __________ is the most widespread cause of infection, but rarely causes human disease.

abortus

139

Brucella ___________ is the most common type seen with disease and is the most prevalent

melitensis

140

What two countries are most affected by Brucella?

Mongolia & Syria

141

Up until 2002, the highest burden of Brucella was in what two states?

Texas & Hawaii

142

T/F: Person-to-person transmission of Brucella is common.

False

Extremely rare, a few cases from direct tissue transplantation

143

**How is Brucella transmitted in the environment?**

-Contaminated by birth products/abortions of infected animals

-Can be spread by inhalation of contaminated dust

-Can survive for long periods of time in dust, dug, slurry, water, soil, carcasses

144

___________ transmission is the most common cause of Brucella exposure to humans. _______ products are more common than meat products to cause infection.

Foodborne

Dairy (i.e soft cheeses, fresh milk and dairy products)

145

Brucella is an intracellular parasite of the ____________ system that does NOT produce an exotoxin.

-reticuloendothelial system (macrophages and phagocytic cells in the lymph nodes and bone marrow)

146

**How does Brucella cause disease?**

1. Macrophages phagocytose Brucella.

2. Phagocytosed Brucella reproduce and inhibit cells critical for life functions

3. Phagocytosed bacteria travel in the blood to organs (ex. Spleen, liver, bone marrow, kidneys, and lymph nodes)

4. Bacteria secretes proteins which elicits an immune response causing granuloma formation

5. Granuloma formations destroy tissue and cause destructive disease

147

Describe the acute presentation of Brucellosis

-Invariable, Undulant Fever (most common symptom)

-Rigors if bacteremic

-Malodorous perspiration (wet hay-like odor)

-Constitutional symptoms (fevers, chills, night sweats, weight loss)

-Chronic fatigue symptoms may develop

-Nonspecific physical exam may see swelling of particular organs (ex. lymphadenopathy, hepatomegaly/splenomegaly)

148

T/F: About 50% of Brucellosis cases are acute

True

149

**T/F: Osteoarticular disease can present as peripheral arthritis, sacroliitis, and spondylitis. **

True

Peripheral arthritis: most common, non-erosive, involves knees, ankles, wrists, and hips, seen in acute infection

Sacroiliitis: inflammation of bones around the sacrum (lower back) seen in acute infection


Spondylitis: inflammation of space between vertebral discs propensity for lumbar spine, difficult to treat

150

____________ system is the most common site of focal brucellosis, which carries a potential risk for _________.

-Reproductive system


-Spontaneous abortion

151

**What are the clinical presentations of Brucellosis in various body systems?**

1. Bones: osteoarticulitis (peripheral arthritis, sacroiliitis, spondylitis)

2. Reproductive system: epididymoorchitis in men, spontaneous abortion

3. Liver: hepatitis (tranaminasemia, abscesses and jaundice-rare)

4. CNS: Meningitis, encephalitis, meningoencephalitis, meningovascular disease, brain abscess, demyelinating syndromes

5. Cardiovascular: endocarditis

152

**Endocarditis is the principal cause of mortality associated with Brucella. How does the disease progress and lead to fatality?**

-overtime the heart forms infective vegetation’s on the valve (usually aortic) that leads to physical changes and decreased functionality

1. Bacteria stick onto a valve of the heart

2. Accumulate more bacteria and thrombotic material (plateletes, fibrin, etc.) that creates a vegetation on a valve


3.Bactetria produce materials (chemicals like chemokines and proteins) with resistance factors against treatment (i.e. antibiotics)

4. Valvular dysfunction (pressure changes, valves stop working, inefficient blood flow)

5. Physical changes in heart that can lead to heart failure

153

Brucella endocarditis is _____ and effects 1-5% of infected individuals. Patients with endocarditis likely have/had underlying cardiac conditions. Most frequently the ______ valve is affected. _______ ventricular failure is most common.

-rare

-aortic

-Left

154

**How does Brucella affect animals?**

-usually infects animals in endemic areas

-asymptomatic with initial infection

-localized reproductive tract (epididymus and orchitis in M and placentitis in F)

-may cause spontaneous abortions and still births

155

With brucellosis Ig_ against the LPS appears during the first week of infection. Ig_ appears during the second week of infection. Both peek at 4 weeks. IgM persists at _______ levels than IgG after 6 months. If Ig_ and Ig_ persist for longer than 6 months then a person has chronic brucellosis.

-IgM (acute factor)

-IgG (chronic factor)

-higher

-IgA and IgG

156

What is the gold standard of for Brucellosis diagnosis and why

-Blood culture (isolation of bacterium from blood or tissue sample) or Bone marrow culture (harder to obtain)

-Propensity for reticuloendothelium

-takes long period of time

157

Titers> _________ plus history of clinical presentation with Brucella are necessary for diagnosis.

1:160

158

**What are some drawbacks to agglutination test (aka milk ring test)?**

-can’t detect B. canis***

-cross reactions possible

-Lack of seroconversion: false negative if patient doesn’t make antibodies

159

**What prevents seroconversion when performing diagnostic testing for Brucellosis?**

1. May too early in the course of infection for the body to produce IgM and IgG

2. Presence of blocking antibodies => “Prozone” phenomenon: prevents agglutination due to excess antigen, excess of non-specific serum factors => false negative

160

**Describe the prozone effect. (Brucella)**

-The body of the infected host produces high amounts of (blocking) antibody that prevents natural Brucella antibodies from binding.

Produces a false negative result upon diagnostic testing due (not detecting antibody of interest)

161

What is the treatment for Brucellosis?

Doxycycline (bacteriostatic) and rifampin for 6 weeks

-Combination is ideal

162

What are general control measures that could be implemented for Brucella?

-Safe farming and good personal hygiene

-PPE (gloves, protective clothing, sanitary tools)

-safe disposal of aborted fetus

-food safety (store soft cheese for 6 months, food acidification to pH<3.5, pasteurize milk (80-85 C) especially if in an area where brucellosis is high, cook meats)

163

What are animal control measures that could be implemented for Brucella?

-choose animals from Brucella free herds, isolate new animals for 30d

-diagnose abortion causation, premature births, and other clinical signs w/ lab assistance

-routine surveillance of herds and flocks (milk ring test)

-vaccination (most successful method for prevention and control)

164

What is the best Brucella surveillance for the four main reservoirs?

Cattle: milk ring test (dairy), blood sample (beef)

Pigs, Sheep, Goats: blood sample

165

What is the milk ring test (MRT)?

-simple and effective, but only works for cows

-drop of hematoxylin-stained antigen into a sample of cow’s milk

If Brucella antibody is present, a blue ring of cream will appear at the top of the tube/glass

166

How did the US Department of Agriculture Cooperative State-Federal Brucellosis Eradication Program try to eliminate Brucella? What is the prevalence of Brucella in domestic herds now?

-Tested animals for Brucella

-Slaughtered any positive animals or animals exposed to positive animals, traced back exposure, vaccinated animals

-Surveillance: MRT, market cattle identification (blood test)

-No longer found in domestic herds in the US

167

What organism causes Q Fever

Coxiella burnetii

168

How does Q fever infect a host?

-Using a passive mechanism, the bacteria survives within the phagolysosome of a macrophage

-Produces spores to withstand harsh environments

-Antigenic variation/phase variation (phase I highlight infectious)

169

What are Q-fever reservoir species?

-Goats, sheep and cattle (main reservoirs)

-Cats

-Rabbits

-Birds

- Ticks

170

How is Q Fever transmitted to humans?

-organism excreted in urine, feces, milk, and birth fluids

-inhalation of the organism from contaminated environments (most common, only need 1-10 organism to be infected)

-raw milk (occasionally)

171

T/F: Coxiella (Q Fever) is one of the most infective species in the world

True

-Only takes 1-10 organisms

-70% morbidity

-potential bioterrorism (especially w, ability to form spores

172

Q. Fever has an incubation period of ________

Most commonly: 20 days (range of 14-39 days)

173

What are the symptoms of Q. Fever?

-Nonspecific symptoms (headache, fatigue, malaise, chills, fevers, night sweats)

-retro-orbital pain

-self-limited febrile illness (2-14d)

-most are asymptomatic

174

**What are the severe complications of chronic Q-fever?**

-endocarditis

-osteomyelitis

-Neuro complications

175

What is the general course of disease for Q fever?

1. Exposure

2. Acute Q Fever (primary infection)

3. Chronic infection (if pregnancy: abortion or chronic carriage, endocarditis, cancer)

176

How is Q fever detected?

Serology to determine antigenic phase

177

What are the antigenic phases of Q fever and how do they relate to the course of disease?

Phase I: acute infectious phase

Phase II: less virulent, susceptible

Chronic infection: High Phase I and Phase II Ab

Acute: high phase II Ab

178

T/F: Phase II antibodies present before phase I in Q Fever.

True

-Phase II is detectable during acute Q fever, whereas high levels of phase I antibodies are detectable during chronic Q fever


-acute is antiphase II IgG >/= 200 and IgM >/= 50

179

What is the treatment for Q Fever?

Doxycycline for 2 weeks