Bonus Lecture (Lecture 15)

Question 1

Name and describe the 2 types of strict human pathogens found in the genus Neisseria

Answer 1

1) Neisseria gonorrhoeae—cause of gonorrhea
2) Neisseria meningitidis—cause of epidemic meningitis

Question 2

What do Neisseria gonorrhoeae and N. meningitidis have in common?

Answer 2

1) Both are gram-negative diplococci (resembling coffee beans)
2) Aerobic and no flagella

Question 3

List 6 characteristics of N. gonorrhoeae

Answer 3

1) Sexually transmitted
2) Characterized by inflammation and purulent discharge
3) Fairly common disease
4) Localization depends upon route of infection
5) Almost always associated with mucosal surfaces
6) Asymptomatic carriage rates are high among women.

Question 4

What are the 4 routes of infection with N. gonorrhoeae?

Answer 4

1) Genital Sex: Male urethra and female cervix.
2) Oral Sex: Throat
3) Anal Sex: Anus
4) Transmission during birth: eye infection of infant

Question 5

Is N. gonorrhoeae symptomatic? If so, in who?

Answer 5

1) Asymptomatic carriage rates are high among women.
-Here asymptomatic means that women do not experience immediate symptoms (e.g. vaginal discharge)
2) Generally 90% of males are symptomatic, but still some are asymptomatic carriers

Question 6

1) How has the rate of gonorrhea changed over time?
2) Although the incidence of disease has declined in US we still have 10 times higher incidence of gonorrhea than other developed countries; why?

Answer 6

1) Disease has been declining in developed countries
(US: 400,000 reported cases/ year, 800K incl. unreported cases.
2) No support system, lack of health coverage, undereducated population, and antibiotic resistance

Question 7

Why are there so many cases of gonorrhea even though it is easily treatable? (3 reasons)

Answer 7

1) Many people do not have discernable symptoms
2) Some do not know they are infected unless sexual contact has symptoms
3) No vaccine

Question 8

What age range has the highest rate of gonorrhea?

Answer 8

Affects 20-24 year-olds the most frequently; reproductively damaging

Question 9

For gonorrhea:
1) Name the primary site of infection and symptoms in males
2) Name the primary site of infection and symptoms in females

Answer 9

1) Infection restricted to the urethra. Symptoms: purulent discharge and dysuria develop after 2-5 day incubation period; ~95% of all infected men have acute symptoms. Other complications are rare.
2) Primary site of the infection is the cervix
Symptoms: vaginal discharge, dysuria, and abdominal pain. Most women are asymptomatic or symptoms are not severe.
-First signs of disease may be serious complications of the untreated infection: Pelvic inflammatory disease, salpingitis, infertility, and ectopic pregnancy.

Question 10

Name 2 uncommon clinical presentations of gonorrhea

Answer 10

1) Gonococcemia: Rare (1-3%), not common in males. Septicemia, infection of skin and joints.
2) Purulent conjunctivitis: Newborns infected during vaginal delivery, requires eyedrops to treat.

Question 11

Name and describe the 4 growth factors of Neisseria

Answer 11

1) Pili: mediate attachment to nonciliated epithelial cells.
2) Por proteins: outer membrane proteins (major porins of Neisseria) that help facilitate bacterial invasion into epithelial cells and prevent degranulation of neutrophils (i.e., phagolysosome fusion)
3) Opacity proteins (Opa proteins): promote intimate binding of epithelial cells
4) Rmp proteins (reduction-modifiable proteins): elicits an antibody response, the antibody that binds to Rmp blocks antibodies to other key surface components

Question 12

1) How is Neisseria diagnosed?
2) How is N. gonorrhoeae diagnosed in males?
3) How is N. gonorrhoeae diagnosed in females?

Answer 12

1) Urine test and/or microscopy and culture
2) Gram-stain is very effective in diagnosing males with N. gonorrhoeae
3) In females, microscopy and culture are required

Question 13

1) What is the main way to treat/ prevent gonorrhea?
2) Is there a gonorrhea vaccine? Why?

Answer 13

1) Antibiotics; penicillin used to be used, now strains resistant to beta-lactams, tetracyclines, erythromycin, and aminoglycosides. Fluoroquinolones such as ciprofloxacin are now used.
2) No vaccine available for N. gonorrhoeae due to lots of antigenic variation among important epitopes (e.g. pilin proteins)

Question 14

Name 6 characteristics of Chlamydia trachomatis

Answer 14

1) Obligate intracellular (Energy/ATP) pathogens
2) Has a unique developmental cycle
3) Causative agent of chronic latent/persistent infections
4) Most common bacterial STI; Known as the ‘Silent’ epidemic
5) Small (Once thought to be viruses), Gram-negative (-/+ Peptidoglycan, rough LPS (no O-antigen))
6) Contain DNA, RNA and ribosomes.

Question 15

Name 3 antibiotics chlamydia is susceptible to

Answer 15

Tetracycline, doxycycline, azithromycin

Question 16

Name and describe the 3 major chlamydia species associated with human disease

Answer 16

1) Lymphogranuloma venereum results in invasive STI
2) Chlamydophila pneumoniae: pneumonia; implicated in atherosclerotic coronary disease. To human, respiratory secretions
3) Chlamydophila psittaci: pneumonia leads to endocarditis which leads to polyarthritis. Zoonotic transmission; inhalation

Question 17

Name the two biological and morphological forms of chlamydiae. Include which is environmentally stable.

Answer 17

1) Elementary Body (EB)
-0.3μm
-Environmentally stable, metabolically inactive
-Attachment and entry
2) Reticulate Body (RB)
-0.8μm
-Environmentally unstable, metabolically active
-Replicative form

Question 18

Describe the developmental cycle of chlamydia

Answer 18

Spreads up the canal. C. trachomatis makes a single inclusion, whereas C. pneumonia and other make multiple inclusions.

Question 19

Describe how chlamydia enters host cells

Answer 19

-Receptor-mediated endocytosis [receptor unknown] through type III secretion: During entry through mucous membranes, EB inject a virulence factor (Tarp) that remodels actin cytoskeleton of the host cell.

Question 20

Describe how chlamydia manipulates host cells (6)

Answer 20

1) EB-containing endosome avoids lysosomal fusion (joins exocytic pathway)
2) Golgi lipids are recruited to the chlamydial inclusion
3) Chlamydial inclusion membrane proteins (Inc) are implicated in numerous host-pathogen interactions
Chlamydiae can inhibit epithelial cell apoptosis
4) Type III secretion: virulence effector proteins are relocated into host cytosol
5) CPAF: degrades host cell MHC I transcription factors
6) Persistence: Allows chlamydiae to survive stressful times

Question 21

1) What is the leading cause of STIs?
2) What are C. Trachomatis serovars D-K associated with?

Answer 21

1) C. trachomatis serovars D-K
2) Chronic latent/persistent infections; clinical manifestation as urogenital infections. Reiter’s syndrome (sexually-acquired reactive arthritis), infertility, urethritis, pelvic inflammatory disease.

Question 22

What is Lymphogranuloma venereum associated with?

Answer 22

1) Small, painless lesion
2) Inflammation & swelling of lymph nodes (buboes)

Question 23

1) When did chlamydia rates go down?
2) In what group is chlamydia most common?

Answer 23

1) Chlamydia rates went down during COVID.
2) Far more chlamydia cases in women, especially in 15-24 year olds. Very concerning since it can affect fertility if untreated.

Question 24

What 3 methods can be used to diagnose chlamydia?

Answer 24

1) Cytologic, serologic or culture findings
2) Direct antigen detection in clinical specimens (MOMP & LPS)
3) Nucleic acid probes (NAATs)

Question 25

What does azithromycin treat? How does it work?

Answer 25

• Used to treat chlamydia
  -Better acid stability and bio-availability
  -Delivered by neutrophils and taken in through pinocytosis (since chlamydia is intracellular)
  -Two 50s binding sites.
  -Via azo-group, azithromycin molecules interact w/ each other

Question 26

Name 4 members of the filovirus genus

Answer 26

1) Marburg
2) Ebola Sudan virus
3) Ebola Zaire virus
4) Ebola Reston virus

Question 27

1) Where was the marburg virus discovered and what is its mortality rate?
2) Where was the ebola sudan virus discovered and what is its mortality rate?
3) Where was the ebola zaire virus discovered and what is its mortality rate?
4) Where was the ebola reston virus discovered and what is its mortality rate?

Answer 27

1) Marburg virus: discovered in an outbreak of hemorrhagic fever in 1967 among employees in a monkey handling facility in Marburg, Germany
-Mortality rate in humans: ~25%
2) Ebola Sudan virus: discovered in an outbreak of hemorrhagic fever in 1976 in Africa (Sudan)
-Morality rate in humans: ~60%
3) Ebola Zaire virus: discovered in an outbreak of hemorrhagic fever in 1976 in Africa (Zaire)
-Mortality rate in humans: ~90%
4) Ebola Reston virus: discovered in an outbreak of hemorrhagic fever in 1989 among
monkeys in a primate center in Reston, VA (USA).
-Related to Ebola Zaire
-High mortality rate in monkeys, but doesn’t cause disease in humans

Question 28

Name 2 category A bioterrorism agents

Answer 28

Ebola and Marburg

Question 29

Describe the structural properties of filoviruses (4)

Answer 29

1) Filamentous, long and thread-like (filo= thread)
negative-strand RNA viruses
2) Enveloped virus with enveloped glycoproteins
3) Virus carries an RNA dependent polymerase within the virion
4) Helical nucleocapsid

Question 30

1) Marburg virus, Ebola Zaire and Ebola Sudan all cause what?
2) What symptoms are experienced from these viruses after one week of incubation?

Answer 30

1) All cause hemorrhagic fever with similar symptoms; they cause, few, if any, asymptomatic infections
2) Profound leukopenia, severe headache, muscle pain, high fever, abdominal pain, vomiting (“vomito negro”-black vomit), severe hemorrhages into the skin (petechiae) and bleeding from nose, GI tract, eyes and GU tract, clot formation in all organs and in the CNS

Question 31

1) Ebola ______ mortality rate is >90%; average of ___% among all strains
2) Name 2 complications reported among ebola survivors

Answer 31

1) Zaire; average of 50% among all strains
2) Mental health, persistence of virus in immune-privileged sites.

Question 32

1) Where do human pathogenic filoviruses come from?
2) Where did Ebla Reston come from and how is it transmitted to humans?
3) How is Ebola spread from person to person?
4) What is one problem Africa is facing that has encouraged the spread of ebola?

Answer 32

1) Human pathogenic filoviruses have all come from central Africa
2) Ebola Reston virus came from monkeys imported from the Philippines which implies that other filoviruses might exist outside of Africa. Presumably transmitted to human primary cases by direct contact with infected animals
3) Ebola is easily spread from person to person by direct contact with virus contaminated fluids (e.g. blood)
4) In African hospitals they reuse needles; this has been a source of transmission

Question 33

1) What started both the 1967 Marburg and 1989 Reston outbreaks?
2) What is the natural reservoir of ebola?

Answer 33

1) Monkey to human transmission started both the 1967 Marburg and 1989 Reston outbreaks
2) Natural reservoir is unknown BUT it may be a fruit bat (recent evidence supports)

Question 34

1) What care is given to filovirus patients?
2) Name 4 potential treatments for filoviruses

Answer 34

1) Supportive care (similar to hospice); rehydration therapy
2) Potential treatments:
a) Blood products, immune/drug therapy
b) 2 monoclonal Ab approved by FDA in 2020
c) Ervebo Vaccine: protective for Zaire strain, approved in 2020. Ages 18+.
d) 2-component vaccine (Zabdeno-Mvabea): ages 1 and up, 2 doses prophylactic.

Question 35

Name the genus and family of the rabies virus

Answer 35

1) Genus: Lyssavirus
2) Family: rhabdoviridae

Question 36

Describe the structure of the rabies virus (4 characteristics)

Answer 36

1) Single-stranded, linear, negative polarity, RNA genome
2) Particle is bullet/ rod shaped. Rhabdos means rod.
3) Single serotype of rabies virus
4) Enveloped

Question 37

1) Describe the host range and tissue tropism of rabies
2) How does the virus enter host cells?
3) What is the typical incubation period for rabies? What contributes to the length of this period?

Answer 37

1) Wide host range and infects all warm-blooded animals; has a narrow tissue tropism (neurotropic)
2) Virus uses acetylcholine receptor to enter host cells.
3) Can vary from 1 week to 1 year, but typically 2-3 months. Body mass and location of bite matter.

Question 38

1) Define Negri bodies
2) Where is rabies found?
3) What is the most common mode of transmission?
4) What are other modes of rabies transmission?

Answer 38

1) Negri bodies: round or oval inclusions in the cytoplasm of nerve cells
2) Found worldwide
3) Zoonotic virus; infected animal bites are the most common way rabies is transmitted
4) Other modes of transmission: Inhalation of rabies containing saliva/ urine (e.g. bat caves).

Question 39

What are the two forms of epizootic rabies?

Answer 39

1) Urban rabies (dogs, cats): most common cause of human rabies in most of the developing world.
2) Sylvatic Rabies (wildlife): since pets in the USA are required to be vaccinated for rabies, most human rabies in the US is acquired from wild animals.

Question 40

1) What are animals are the most common vectors for rabies?
2) Is human to human transmission rare? If so, why?

Answer 40

1) Skunks, bats, raccoons, foxes, and coyotes
2) Extremely rare because humans are a dead end host (quickly killed by virus)

Question 41

What are the two ways in which rabies symptoms can present? How are they characterized?

Answer 41

1) Furious rabies: characterized by hyperactivity and hallucinations.
2) Paralytic rabies: characterized by paralysis and coma.

Question 42

1) Do all people bitten by an infected animal get rabies?
2) When does rabies become fatal?
3) What is the fatal symptom?

Answer 42

1) Not all people bitten by an infected animal get rabies
2) 99% fatal once symptoms show up
3) Rabies causes an acute, fatal encephalitis

Question 43

Name 3 things that contribute to the variability in rabies incubation period

Answer 43

1) Amount of virus inoculated
2) Distance from the site of inoculation to the brain
3) Age: incubation period is usually shorter in children than in adults

Question 44

Name and describe the 4 stages of rabies

Answer 44

1) Incubation phase: asymptomatic, low titer, virus in the muscle
2) Prodrome phase: lasts 2-10 days; tingling at site of infection (wound), anxiety, nausea, vomiting, headache and fever
3) Neurologic phase: anxiety becomes more intense, muscle spasms/pain, combativeness, hallucinations, increased perspiration/salivation/lacrimation.
-Swallowing causes laryngopharyngeal spasms, so patient drools rather than swallowing saliva; ”foaming at the mouth”
-Hydrophobia (fear of water) is the most characteristic symptom of (furious) rabies
-Sometimes aerophobia (fear of drafts of fresh air)
4) Depressive/paralytic phase: Last 3-5 days; characterized by convulsive seizures, coma, respiratory paralysis and death
-Death usually occurs within 21 days of symptoms onset.

Question 45

1) How often does recovery from rabies occur?
2) If recovery does occur, what is likely?

Answer 45

1) Recovery almost never occurs
2) If patient survives they typically have severe CNS damage

Question 46

1) What treatment do patients receive for rabies?
2) Is there a rabies vaccine?
3) What other rabies treatments are available?
4) How can rabies be controlled in animals?
5) How can rabies be prevented in humans?

Answer 46

1) Primary therapy once you contract the symptoms is palliative
2) Two effective killed (inactivated vaccines)
3) Passive immune therapy: Human Rabies Immune Globulin (HRIG)
4) Vaccination of dogs/cats; vaccination of high risk wild animals using bait vaccines
5) Vaccines, medicines and technologies have long been available to prevent death from rabies.