M- Gonorrhea, Chlamydia, Urethritis

Question 1

21 yo male presents to a family practice clinic
complaining of 5 days of clear to slightly cloudy
penile discharge, after multiple episodes of
unprotected sexual contact with several female
partners about 2 weeks ago. Statistically, his
urethritis is most likely due to what?

Answer 1

Chlamydia is the most common cause of urethritis in the US

Question 2

For a person presenting with urethritis [most likely chlamydia or gonorrhea] what tests are appropriate to run?

Answer 2

1. Nucleic acid amplification test of urine for
   GC/Chlamydia
2. Culture for GC using chocolate agar
3. Empiric therapy with ceftriaxone and azithromycin
4. HIV rapid screen

Question 3

Six months later, a patient previously treated for gonorrhea returns to clinic with similar symptoms. He just got back from spring break, and is a bit fuzzy on what he did,
and with whom. You review the chart and it turns
out that he had N. gonorrhoeae confirmed by
NAAT of the urine last time. You repeat this same test, and get the same result. Why?

Answer 3

Because you can get reinfected with gonorrhea

Question 4

If a person presents with recurrent, disseminated gonorrhea, what problem is present in the host?

Answer 4

They are unable to make the last steps of complement [C5-9]

Question 5

What organism is associated with the following descriptions?

A. “Cottage cheese” 
B. Strawberry cervix 
C. Clue cells 
D. Chandelier sign 
E. Neonatal pneumonia 
F. Blindness- fly vector 
G. Intracellular GN diplococci

Answer 5

A. candidiasis
B. Trichomonas vaginalis
C. gardnerella vaginalis [bacterial]
D. PID
E. C. trachomatis D-K
F. C. trachomatis A-C
G. N. gonorrhea

Question 6

What is the only host for N. gonorrhea and C. trachomatis?
What age group is most affected?
How is occurrence changing over time?

Answer 6

Humans are the only host.
Most commonly affects people under the age of 25.

GC is stable, but incidence of chlamydia has been rising

Question 7

What are the 2 main Neisseria pathogens? How do they differ in terms of structure?

Answer 7

N. meningitidis = encapsulated

N. gonorrhea = non-encapsulated

Question 8

Describe the microbiological features of N. gonorrhea.

[gram staining, shape, capsule? Oxidase? catalase? structure?]

Answer 8

1. G- diplococci [kidney bean shaped]
2. NOT encapsulated
3. Catalase +
4. oxidase +
5. produce acid only from the oxidation of glucose
6. inner and outer membrane with thin peptidoglycan layer but NO LPS
7. LOS- oligosaccharide

Question 9

What does N. gonorrhea need for growth?

What agars can be used to culture?

Answer 9

It is a fastidious aerobic organism that for growth requires:

• high humidity
• high CO2
• 35 to 37 degrees

Chocolate agar- for sterile sites [blood, joints, CSF]
Thayer-Martin for everywhere else because it has the chocolate agar base but added vancomycin to inhibit G+, colistin to inhibit enteric and TMP-SMX to inhibit proteus

Question 10

What makes gonorrhea different form other gram negative bacteria in terms of structure?

Answer 10

They have LOS instead of LPS in the outer membrane.

LOS contributes to virulence and inflammation.

Question 11

What are the major antigens on N. gonorrhea?

Answer 11

LOS
pili
OMPs

Question 12

How is gonorrhea transmitted?
What is the transmissibility after contact for a male? Female?
What increases risk of infection?

Answer 12

Person-to-person [sexually]
N. gonorrhea can use pili to attach to sperm and “hitch a ride”.

Transmissibility to males after contact with an infected person =20%
Females =50%

Increased number of sex partners increases risk of infection. Most people with the infection are asymptomatic or minimally symptomatic.

Question 13

What are the virulence factors associated with N. gonorrhea?

Answer 13

1. Pili
2. porin proteins [PorB]
3. Opa and Rmp
4. LOS
5. IgA1 protease
6. Transferrin-binding proteins
7. natural competence

Question 14

How do pili on N. gonorrhea confer virulence?

Answer 14

1. allow bacteria to bind host epithelial cell receptors [no pili, no infection]
2. conserved carboxyl terminus, but highly variable amino terminus allows antigenic variation of the pilin proteins making immunity strain specific [and difficult to make vaccines for]
3. phase variation for more antigenic variability and immune evasion
4. inhibit phagocytosis by neutrophils

Question 15

How do porin proteins like PorB on N. gonorrhea confer virulence?

Answer 15

1. pores in the outer membrane acquire substrates for the bacteria
2. strain to strain variation in the pores allow immune evasion
3. pore acts as an adhesin to promote entry into the epithelial cell
4. inhibits degranulation of neutrophils
5. inhibits phagolysosomal fusion by interfering with cell signaling

Question 16

What is the function of Opa and Rmp on N. gonorrhea?

Answer 16

1. attach to host cells

2. prevent attachment of bactericidal antibodies to the bacterial cell surface

Question 17

What is the function of LOS on N. gonorrhea?

Answer 17

1. directly toxic to urethral epithelial cells and to epithelial cells of the fallopian tubes.
2. antigen undergoes phase variation and can be modified so bactericidal antibodies can’t bind to it

Question 18

What is the function of IgA1 protease for N. gonorrhea?

What is the function of transferrin-binding proteins?

Answer 18

It leads to immune evasion by destroying mucosally secreted specific antibodies

Transferrin-binding proteins allow the gonorrhea to scavenge Fe from host stores for bacterial virulence.

Question 19

What does it mean that gonorrhea is naturally competent?

Answer 19

They can take up DNA from the environment easily leading to genetic variability.

Question 20

What is the earliest and most effective method of inflammatory control and phagocytosis of a gonorrhea infection?

Answer 20

Neutrophils

Question 21

What is the immune response to reinfection by N. gonorrhea?

What limits the efficacy?

Answer 21

Antibody response (targets pili, Opa, LOS)

Anti-LOS antibodies trigger complement–> neutrophil chemotaxis

Efficacy of the Ab response is limited by:

1. Phase/antigenic variation
2. Rmp can block bactericidal response
3. Sialylation of LOS -masks antigen, prevents recognitionby Factor H, and inhibits complement activation by alternative pathway

Question 22

What is the pathogenesis of N. gonorrhea?

Answer 22

1. Bacteria is introduced into the body and attaches
   to/invades mucosal cells using:
   -Pili, porin proteins, Opa proteins
2. Evades the immune system
3. Local invasion via replication in columnar epithelial cells and within phagocytic vacuoles
4. LOS stimulates release of inflammatory cytokines (TNFα) causing symptoms
5. Systemic invasion if there is avoidance of complement system

Question 23

What are the diseases associated with infection by N. gonorrhea?

Answer 23

1. Urethritis
2. Cervicitis
3. Pelvic inflammatory disease
4. Pharyngitis
5. Disseminated gonococcal infection [dermatitis-arthritis]
6. Epididymitis
7. Conjunctivitis

Question 24

What is the MOST common presentation of gonococcus in men? What is the incubation period? What are the symptoms?
Where can the infection spread?

Answer 24

Urethritis develops after 2 to 45 days since exposure.
The man will present with:
-stinging dysuria
- purulent discharge from the urethra

From here the infection can spread to cause:
epididymitis
prostatitis
orchitis

Question 25

What is the MOST common presentation in women with gonorrhea?
What can this infection lead to?

Answer 25

Cervicitis with:

1. vaginal discharge
2. abdominal pain
3. frequent urination

Ascending infections can lead to PID

Question 26

What organisms can cause PID?
What 3 things does PID put you at risk for?
What are risk factors for the development of PID?

Answer 26

a