Chapter 29

Question 1

Which Bordetella species are responsible for human disease?

Answer 1

Bordetella pertussis, parapertussis, bronchiseptica, and holmesii.

Question 2

Bordetella pertussis is responsible for what? Bordetella parapertussis is responsible for what?

Answer 2

Bordetella pertussis is responsible for pertussis, “whooping cough,” and Bordetella parapertussis is responsible for a milder form of pertussis.

Question 3

Bordetella bronchiseptica is responsible for disease in whom? And occasionally in whom?

Answer 3

Responsible for respiratory disease in dogs, swine, lab animals, and occasionally pertussis-like symptoms in humans.

Question 4

Bordetella holmesii is a rare cause of what? It may also cause what?

Answer 4

Rare cause of sepsis; may also cause pertussis (whooping cough)

Question 5

Bordetella species are differentiated on the basis of what?

Answer 5

Bordetella species differentiated on basis of growth characteristics, biochemical reactivity, and antigenic properties.

Question 6

The four pathogenic species (Bordetella pertussis, parapertussis, bronchiseptica, and holmesii) differ phenotypically, but are ________.

Answer 6

The four pathogenic species differ phenotypically but closely related genetically. They may all be variants of the same species – differ in expression of virulence genes.

Question 7

Bordetella pertussis has what kind of nutritional requirements? Why can’t it grow on routine lab media? It can, however, grow (only!) on specialized media supplemented with ________. What media is used for its transport and growth? Is its growth slow? “Negative” cultures are kept for how long? Is Bordetella pertussis motile? Does it ferment carbohydrates?

Answer 7

Simple nutritional requirements, but highly susceptible to toxic substances in routine media. Grows only on specialized media supplemented with charcoal, starch, blood or albumin to absorb toxic substances – Regan-Lowe media used for transport and growth. Slow growth, typically 3-7 days for isolation – “negative” cultures kept up to 12 days. Non-motile. Does not ferment carbohydrates.

Question 8

Bordetella parapertussis, bronchiseptica, and holmesii are less fastidious than B. pertussis and can grow on ________.

Answer 8

Bordetella parapertussis, bronchiseptica, and holmesii – less fastidious; can grow on selective and non-selective media (blood agar, MacConkey agar).

Question 9

Bordetella species have a ________ O antigen and a ________ K antigen, which can be used for what?

Answer 9

Bordetella species have a genus specific O antigen and strain specific, heat labile, K antigens – K (capsular) antigens used for differentiating isolates for epidemiologic purposes.

Question 10

Infection with B. pertussis/development of whooping cough, requires what?

Answer 10

Exposure to organism; bacterial attachment to ciliated epithelial cells; proliferation of organism; production of localized tissue damage; systemic toxicity.

Question 11

Bacterial attachment to ciliated epithelial cells are mediated by ________.

Answer 11

Peractin and filamentous hemagglutinin – promote binding to sulfated glycolipids on the membranes of ciliated respiratory cells; ability to bind to and agglutinate erythrocytes; interaction with these adhesins also key to inducing survivable phagocytosis – intracellular survival of B. pertussis; protected from humoral antibodies (may account for persistent carriage?).

Question 12

Toxins mediate ________ and ________ manifestations.

Answer 12

Toxins mediating localized and systemic manifestations.

Question 13

Which toxin is major virulence factor of B. pertussis? [________ toxin – major virulence factor of B. pertussis: ________ and ________ disrupted; inhibits ________; increased ________ and ________ – characteristic of ________ stage of pertussis.]

Answer 13

Pertussis toxin – major virulence factor of B. pertussis: adenylate cyclase and cell regulation disrupted; inhibits phagocytic killing; increased respiratory secretions and mucous production – characteristic of paroxysmal stage of pertussis.

Question 14

Which toxin is heat labile and probably responsible for localized tissue destruction in human infections?

Answer 14

Dermonecrotic toxin – heat labile toxin probably responsible for localized tissue destruction in human infections.

Question 15

Tracheal cytotoxin has a specific affinity for what type of cells? It inhibits ________ at LOW concentrations and causes ________ at HIGH concentrations. It interferes with ________. It stimulates release of ________, which leads to what?

Answer 15

Tracheal cytotoxin has specific affinity for ciliated epithelial cells; inhibits cilia movement at low concentrations; causes extrusion of ciliated cells at high concentrations; interferes with DNA synthesis – impairs regeneration of damaged cells; process disrupts clearance mechanism of respiratory tree leading to distinctive pertussis cough. Stimulates release of cytokine interleukin-1 which leads to fever.

Question 16

Bordetella pertussis is a ________ disease. Does it have any other reservoir?

Answer 16

Bordetella pertussis is a human disease – no recognized animal or environmental reservoir.

Question 17

After vaccine introduction in 1949, Bordetella pertussis incidence ________ in the U.S. However, worldwide, it is still ________.

Answer 17

Incidence reduced significantly after vaccine introduced in 1949 – 10,000-20,000 deaths/year in U.S. prior to availability of vaccine. Still endemic worldwide – >16,000,000 cases annually; 200,000-400,000 deaths per year.

Question 18

Incidence of Bordetella pertussis is relatively low in the U.S., but over the last decade has ________.

Answer 18

Incidence in U.S. has risen dramatically in U.S. over last decade.

Question 19

Historically B. pertussis considered a pediatric disease – majority of infections in children < 1 year of age. However, the recent dramatic increase in incidence of disease in older children and adults is probably attributed to ________.

Answer 19

Recent dramatic increase in incidence of disease in older children and adults – waning immunity over time?; no vaccine?; better diagnostic methods?

Question 20

Which age group is at greatest risk for severe disease and death, and continues to have the highest reported rate of pertussis?

Answer 20

Infants aged < 1 year old – greatest risk for severe disease and death; continue to have the highest reported rate of pertussis

Question 21

In Oregon, infants have the highest risk of pertussis-related complications and death, but in recent years, the GREATEST INCREASE has been in whom?

Answer 21

The greatest increase in incidence in recent years has been in adolescents and adults.

Question 22

How is B. pertussis infection initiated? Bacteria attach and proliferate on which cells?

Answer 22

Infection initiated by inhalation of infectious aerosols; bacteria attach and proliferate on ciliated epithelial cells.

Question 23

What is the first stage of B. pertussis disease? How long is incubation? How long does it last? What are the symptoms at this stage? Patients in this phase pose THE HIGHEST risk to whom? Why?

Answer 23

Catarrhal stage (first of three stages) develops after 7-10 day incubation and lasts 1-2 weeks – resembles common cold with serous rhinorrhea, sneezing, malaise, anorexia, low-grade fever; patients in this phase pose highest risk to contacts, most contagious – peak number of bacteria; disease not diagnosed at this point.

Question 24

What is the second stage of B. pertussis disease? When does it develop? How long does it last? Ciliated epithelial cells are extruded from where, impairing what? This stage is characterized by what classic symptom? Mucous production in ________ is common and partially responsible for causing ________. Paroxysms are frequently terminated with ________. Marked ________.

Answer 24

Paroxysmal stage (second stage): develops at 1-2 weeks post infection; 2-4 weeks duration; ciliated epithelial cells extruded from repiratory tract – clearance of mucous impaired; characterized by onset of classic whooping cough paroxysms (40 to 50 paroxysms per day at peak of illness); mucous production in respiratory tract common and partially responsible for causing airway obstruction; paroxysms frequently terminated with vomiting and exhaustion; marked lymphocytosis.

Question 25

What is the third stage of B. pertussis disease? When does it start? How long can it persist? What happens to the paroxysms? What secondary complications can occur at this stage?

Answer 25

Convalescent stage (third stage): starts 2-4 weeks post infection; can persist for 3-4 weeks or longer; paroxysms decrease in number and severity; secondary complications can occur at this stage – pneumonia, convulsions, subconjunctival bleeding.

Question 26

Classic presentation of B. pertussis disease may not be seen in whom? Some evolution through three stages may be seen, but what may be absent? Patients may have a history of chronic persistent cough with or without what? – also know as ________.

Answer 26

Classic presentation may not be seen in patients with partial immunity or children under six months – some evolution through three stages may be seen, but paroxysmal coughing and lymphocytosis may be absent; patients may have history of chronic persistent cough with or without vomiting – “Hundred Day Cough”

Question 27

For B. pertussis specimen collection, best specimen is ________. The yield from nasopharyngeal swabs is much lower, so collect on ________. Why not cotton swabs?

Answer 27

Best specimen is nasopharyngeal aspirate; yield from nasopharyngeal swabs much lower; collect on synthetic fiber swabs (calcium alginate, rayon, dacron) – cotton swabs contain fatty acids which are toxic to Bordetella.

Question 28

B. pertussis specimen should be transported, ASAP, in ________ media. Specimen must remain ________ in trasport. Should be inoculated onto ________ agar.

Answer 28

Transported, ASAP, in Regan-Lowe transport media – must remain moist in transport; inoculated onto Bordet-Gengou, Regan-Lowe, or charcoal-horse blood agar.

Question 29

The Direct Fluorescent Antibody (DFA) stain uses antibodies directed against what? Why have many labs discontinued this test? ALL stain results must be confirmed with what?

Answer 29

DFA stain – specimen smeared on slide, air dried, heat fixed and stained with fluorescein labeled antibodies directed against B. pertussis and parapertussis. – low sensitivity and specificity, many false negative tests (more labs have discontinued this test); all stain results must be confirmed with culture.

Question 30

To culture B. pertussis, ________ or ________ media is incubated at what temperature in a what environment? Prolonged incubation is ________ – colonies rarely visible in less than ________. Culture incubated for ________ before reported as “no growth.” Most hospital laboratories refer this test to ________ for culture. ________ sensitivity test (fewer than half of infected patients will have ________.)

Answer 30

Bordet-Gengou or Regan-Lowe media incubated at 35C in humid environment. Prolonged incubation required – colonies rarely visible in less than 3 days; culture incubated for up to two weeks before reported as “no growth;” most hospital laboratories refer this test to State Public Health depeartments for culture; low sensitivity test (fewer than half of infected patients will have positive cultures.)

Question 31

Which test for pertussis is gaining in popularity? Why?

Answer 31

Nucelic Acid Amplification (molecular methods): PCR tests for pertussis gaining popularity – high sensitivity and specificity; rapid results (available in 4-8 hours); commercial test kit commonly available; no FDA approved test kits currently available.

Question 32

B. pertussis has characteristic microscopic and culture morphology on selective media and has reactivity with specific antisera – agglutination tests, DFA, PCR. Tests used to differentiate B. pertussis from parapertussis: oxidase, urease, and growth on blood agar, and PCR. B. pertussis is oxidase ________ and parapertussis is urea ________ and grows on ________ agar.

Answer 32

B. pertussis is oxidate positive and parapertussis is urea positive, growth on sheep blood agar.

Question 33

Serology – significant rise in antibody titer between ________ and ________ serum (four-fold rise) or an initially high result indicative of ________.

Answer 33

Significant rise in antibody titer between acute and convalescent serum (four-fold rise) or an initially high result indicative of recent infection.

Question 34

B. pertussis treatment is primarily ________. Nursing supervision during ________ and ________ stages. Antibiotics (erythromycin) typically most effective during ________ stage to limit spread to other susceptible individuals. Convalescence dependent on rapidity and degree to which ________.

Answer 34

Treatment is primarily supportive. Nursing supervision during paroxysmal and convalescent stages. Antibiotics (erythromycin) typically most effective during catarrhal stage to limit spread to other susceptible individuals. Convalescence dependent on rapidity and degree to which ciliated epithelial cells regenerate.

Question 35

B. pertussis vaccine is a ________ vaccine and have been available for approximately 50 years. Commonly administered in combination with vaccines for ________ and ________. How effective is the vaccine in eliminating pertussis? What are the concerns regarding this whole cell vaccine?

Answer 35

Whole cell inactivated vaccines have been available for approximately 50 years. Commonly administered in combination with vaccines for diphtheria and tetanus (DPT vaccine). Highly effective (80-85%) in eliminating pertussis. Concerns regarding associated side effects of whole cell vaccine has limited its acceptance – localized inflammation, fever, seizures.

Question 36

Multivalent acellular pertussis vaccines have been developed that are as effective as whole cell perparations without ________. Multiple acellular vaccines licensed in U.S. Combined with vaccines for ________ and ________ – administered at 2, 4, and 6 months with boosters at 15-18 months and 4-6 years. Additional boosters recommended at subsequent ten year intervals.

Answer 36

Multivalent acellular pertussis vaccines have been developed that are as effective as whole cell perparations without the side effects. Multiple acellular vaccines licensed in U.S. Combined with vaccines for diphtheria and tetanus (DTaP) – administered at 2, 4, and 6 months with boosters at 15-18 months and 4-6 years. Additional boosters recommended at subsequent ten year intervals.

Question 37

Immunity from B. pertussis vaccination is not 100% effective and wanes in about ________, hence the need for boosters.

Answer 37

Immunity from vaccination is not 100% effective and wanes in about five years, hence the need for boosters.

Question 38

Antibiotics – pertussis is ________, so antibiotics are recommended for prophylaxis in select situations – ________ of symptomatic patients. ________ is the drug of choice.

Answer 38

Pertussis highly contagious; antibiotics recommended for prophylaxis in select situations – family members of symptomatic patients. Erythromycin drug of choice.

Question 39

Bordetella parapertussis is responsible for 10-20% of ________ occurring ________ in the U.S.

Answer 39

Bordetella parapertussis responsible for 10-20% of cases of mild pertussis occurring annually in U.S.

Question 40

Bordetella bronchiseptica causes ________ primarily in animals and is associated with colonization of the human ________ and ________ disease.

Answer 40

Bordetella bronchiseptica causes respiratory disease primarily in animals; associated with colonization of human respiratory tract and bronchopulmonary disease.

Question 41

Bordetella holmesii is a rare cause of ________ and is associated with ________.

Answer 41

Bordetella holmesii rare cause of human infections. Associated with bacteremia, endocarditis, and rare RTI.

Question 42

Bordetella parapertussis, bronchiseptica, and homesii – which species are easily isolated on conventional media? Which is slow growing, more difficult to culture?

Answer 42

B. parapertussis and bronchiseptica are both easily isolated on conventional media. B. holmesii is slow growing, more difficult to culture.

Question 43

The genus Francisella consists of which two species? Which one is the uncommon opportunistic pathogen?

Answer 43

F. tularensis and F. philomiragia. F. philomiragia is the uncommon opportunistic pathogen.

Question 44

F. tularensis consists of which four sub-species?

Answer 44

F. tularensis sub-species tularensis, sub-species holartica, sub-species mediaasiatica, sub-species novicida.

Question 45

Which F. tularensis sub-species is the most important in the U.S./member of Francisella genus?

Answer 45

F. tularensis sub-species tularensis type A is the most important.

Question 46

F. tularensis sub-species tularensis type A is further subdivided into…?

Answer 46

It is further subdivided into Type A west and Type A east.

Question 47

Which F. tularensis sub-species is found throughout the Northern hemisphere – most important in Europe and Asia?

Answer 47

F. tularensis sub-species holartica type B.

Question 48

Which F. tularensis sub-species are rarely associated with disease?

Answer 48

F. tularensis sub-species mediaasiatica and novicida rarely associated with disease.

Question 49

Which F. tularensis strains are most commonly associated with exposure to lagamorphs (rabbits and hares) and cats?

Answer 49

F. tularensis type A

Question 50

Which F. tularensis strains are associated with rodents and cats but not lagomorphs?

Answer 50

F. tularensis type B (holartica)

Question 51

Infections most commonly caused by biting arthropods (ticks, dear flies, other biting insects) are more common with ________ than with ________.

Answer 51

more common with type A than with type B

Question 52

Which strains are associated with higher mortality rates?

Answer 52

F. tularensis type A east

Question 53

F. tularensis was originally known as ________, but renamed after Edward Francis – current taxonomy is Francisella tularensis. F. tularensis is established as an important ________ – causative agent of ________ (glandular fever, rabbit fever, tick fever) in animals and humans.

Answer 53

Originally known as Bacterium tularensis – first identified in 1912; pathogen of rodents in Tulare County, California. Established as an important human pathogen – causative agent of Tularemia (glandular fever, rabbit fever, tick fever) in animals and humans.

Question 54

F. tularensis is a very small, faintly staining, gram negative ________. Is F. tularensis motile or non-motile? F. tularensis has a ________ capsule. It has ________ growth requirements – most strains require enriched media containing ________; is a ________ aerobe; is a fermenter or non-fermenter?; is a slow grower, minimum of ________ for growth.

Answer 54

Very small, faintly staining, gram negative coccobacilli. Nonmotile. Thin lipid capsule. Fastidious growth requirements – most strains require enriched media containing cysteine; strict aerobe; non-fermenter; slow grower, minimum of three days for growth.

Question 55

F. tularensis is an ________ parasite that can survive for prolonged periods in ________ by inhibiting ________ fusion. Pathogenic F. tularensis strains possess an ________ – loss of ________ associated with decreased virulence.

Answer 55

Intracellular parasite that can survive for prolonged periods in macrophages – organisms inhibits phagosome-lysosome fusion. Pathogenic strains possess an antiphagocytic capsule – loss of capsule associated with decreased virulence.

Question 56

F. tularensis has a worldwide distribution, but highly virulent strains are found only in ________. 100-200 cases reported per year mostly in ________ – (which three states?). F. tularensis disease is not reported in ________ regions – (name the three places).

Answer 56

Worldwide distribution. Highly virulent strains found only in U.S. – 100-200 cases reported per year mostly in lower midwestern states – Arkansas, Missouri, Oklahoma. Disease not reported in southern regions – Central and South America; Australia.

Question 57

F. tularensis is rare, with approximately 200 cases annually in the U.S. – ranked second in the U.S. as a cause of ________ infections, behind ________. Ranked third worldwide, behind ________ and ________.

Answer 57

Rare, approximately 200 cases annually in the U.S. Ranked second in the U.S. as a cause of laboratory-associated infections – behind Brucellosis. Ranked third worldwide – behind Brucellosis and Typhoid.

Question 58

F. tularensis is found in many wild mammals, domestic animals, birds, fish, blood-sucking arthropods and in contaminated water. The most common reservoirs in the U.S. are ________.

Answer 58

Most common reservoirs in the U.S. are rabbits, ticks, and muskrats.

Question 59

Human infection acquired from the bite of an infected hard-shell tick or from contact with an infected animal or pet that has had contact with an infected animal. Tularemia is an infection common in wild rodents transmitted to humans by contact with ________. Can also be acquired from consumption of ________ or from inhalation of ________.

Answer 59

Tularemia is an infection common in wild rodents transmitted to humans by contact with animal tissues or ticks. Can also be acquired from consumption of contaminated meat or water or from inhalation of infectious aerosol.

Question 60

F. tularensis is highly infectious. Infection requires __________ organisms when exposure is from an arthropod bite, or approximately ________ organisms when inhaled – must larger dose required for infection by ingestion, ________. Listed as a ________ by CDC Select Agent Program.

Answer 60

<10 organisms; 50 organisms; 10^8; Category A BioTerrorism agent

Question 61

The reported incidence of F. tularensis disease is low, but the infectivity rate may be much higher than reported. Most infections occur during ________ months when exposure to hard-shell ticks is greatest, or in ________ when hunters are exposed to infected animals – incidence of disease increases significantly when ________ population proliferates.

Answer 61

summer; winter; tick

Question 62

People at greastest risk of F. tularensis infection are ________.

Answer 62

hunters, people exposed to ticks, and laboratory personnel

Question 63

F. tularensis symptoms develop abruptly after a ________ day incubation period – fever, chills, malaise, fatigue.

Answer 63

3-5

Question 64

F. tularensis disease subdivided into (7) different forms based on clinical presentation – what are they?

Answer 64

Ulcerglandular tularemia, oculoglandular tularemia, glandular tularemia, typhoidal tularemia, oropharyngeal tularemia, gastroentestinal tularemia, pneumonic tularemia