Lecture 10 Neisseria

Question 0

What does N. Meningitidis cause?

Answer 0

fatal meningitis and meningococcemia ( 200,000 deaths world-wide)

Question 1

What are the two major pathogenic Neisseria species ?

Answer 1

1) N. Meningitis 2) N. gonorrhoeae Gram-negative diplococci

Question 2

How many deaths does gonorrhea cause?

Answer 2

650,000 and almost 300,000 cases of pelvic inflammatory disease/ yr US (stable number)

Question 3

What are the characteristics of Neisseriae?

Answer 3

They are aerobic or microaerophilic, gram negative diplococci. They have adjacent sides being flattened together (coffee bean :)

Question 4

What does both N. meningitides and N. gonorrhoeae cause?

Answer 4

Purulent infections, characterized by pus ( live and dead PNS, and bacteria)

Question 5

Where does N. Meningitidis (meningococcus) colonize?

Answer 5

Asymptomatic colonization in the nasopharynx is common in healthy individuals.
Also common cause of serious bacterial meningitis (infection of the fluid and lining of the brain and spinal cord).
** Most common in children, second in adults. (Swift of progression from good to life threatening disease measured in hours)

Question 6

What is meningococcemia?

Answer 6

Rapidly progressing bacteremia and sepsis. ( also causes a related disease by N. meningitidis)

Question 7

What are the virulence factors of Major N. meningitidis

Answer 7

1) Fimbrae (Mediate attachment to nasopharynx mucosal epi. cells and resist phagocytosis)
2) Capsule (blood and CNS isolates)
- Anti-phagocytosis
- Antigenic differences between strains
3) IgA protease
4) “Blebs” of LPS

Question 8

Why is Endemic meningococcal disease occur worldwide and epidemics common to developing countries (like sub-Saharan Africa)?

Answer 8

N. meningitidis is spread by respiratory droplets typically among individuals with prolonged contact (e.g family members, soldiers, students..etc)

Question 9

Who are the natural carriers of N. meningitidis?

Answer 9

Humans are the only natural carriers of N. meningitidis and approx. 10% of individuals are asymptomatic carriers at any given time.

Question 10

What are the characteristics of invasive N. meningitidis ?

Answer 10

Invasive N. meningitidis strains all have anti-phagocytic capsules (Encapsulated strains sometimes gain access to the blood stream)

• If individual has no opsonizing(lack) Abs to strain bacteria will multiply and cause disease (More susceptible if you lack opsonizing Ab)
• Primary affects young children!

Question 11

What are the consequences of a susceptible person that has no opsonizing Abs?

Answer 11

The encapsulated strains may be able to move across the lining of the nose & throat and into blood. Once in blood and not opsonized and phagocytosed it will multiply rapidly –> Bacteremia !

Note: Individuals may have been further compromised by a recent upper respiratory infection or damage (e.g smoking)

Question 12

What is the major window of susceptibility in children?

Answer 12

It occurs as maternal Ig G levels decline and their own humoral immunity is still developing.

Question 13

What happens what people develop meningococcal sepsis?

Answer 13

• The bacterial multiply very rapidly in blood so that very large numbers are present and large quantities of ENDOTOXIN are released in “blebs” of the outer membrane.
• These toxins activate monocytes to produce cytokines (TNF-a and IL 6)
• The resulting “systemic inflammation” Causes:
  1) BP to decrease and blood circulation decreases.
  2) Disseminated intravascular coagulation (DIC).
  3) Septic shock

Question 14

What happens when people develop meningitis?

Answer 14

The bacteria grow less rapidly than meningococcal septicemia.

• The bacteria have time to cross from blood into fluid and membranes surrounding the brain.
• The bacteria proliferate and large amount of endotoxin stimulates inflammatory cascade locally in CNS tissue and systemically.
• Result: symptoms and pathology of meningitis!

Question 15

What is a notable feature of N. meningitidis?

Answer 15

• Meningococci constantly “bleb” off large sections of their outer membrane, which contain LPS (endotoxin).
• Intense vesicle formation is a notable feature!

Question 16

What is the treatment of meningococcal infections?

Answer 16

• 50-75% of meningococcal infections are meningitis, the rest is meningococcemia (sepsis).
• Sepsis is more dangerous and 40 % can still die with treatment.
• Without prompt treatment mortality is 100%
• Meningococcal meningitis less harmful, with treatment 10% die of disease.
• Between 10-20% of survivors develop permanent neurological sequelae.

Question 17

How is prevention achieved for meningococcal disease?

Answer 17

Through 2 ways:

1) Antimicrobial prophylaxis (for those in close contact w/ carrier)
2) vaccination

Question 18

What is the relatively new vaccine (2005) available?

What are its affects?

Answer 18

• IT is the Quadra-valent conjugate vaccine.
• It works poorly in young children (<2 yr)
• recommended for children over 10 and for travelers to countries in which disease is epidemic or have a high endemic rate (Africa)

Question 19

What are the main microorganisms that cause bacterial meningitis?

Answer 19

1) Step. Pneum
2) H. Influenza
3) N. Meningitidis
* All have capsules

Question 20

What are the viruses that cause lymphocytic meningitis?

Answer 20

1. Mumps
2. coxsackie
   3) EBV
   4) Polio

Question 21

What are the microorganisms that cause chronic granulomatis meningitis?

Answer 21

1) M. Tuberculosis
2) T. Pallidum
3) cryptococcus

Question 22

What are the microorganisms that cause encephalitis?

Answer 22

Bacterial:

1) listeria
2) treponema
3) borrelia

Viruses:

1) Herpes
2) Polio
3) Measles
4) CMV
5) HIV

Fungi:

1) Cryptococcus
2) Candida

Prion:
1) CJD

Question 23

What are the normal hard oral species of Neisseria?

Answer 23

N. sica and N. perflava

Question 24

What are some characteristics of N. meningitidis?

Answer 24

• Very fragile, drying kills, hard to grow.
• Respiratory spread (Short distance before drying)
• Ice berg effect. (90% infected, 10% get disease)
• Poor blood clearance = increase LPS
• Meningococcemia –> Trombi/Rash/Shock = 6-8 hr fatal
• Meningitis–> Headache, stiff neck, high fever.

Question 25

What is the most commonly STI in the US?

Answer 25

Infection w/ N. gonorrhoeae (gonococcus)

• Rate of gonorrhea infections have basically plateaued since the late 1990.
• Each yr 650,000 people in the US are infected.

Question 26

What are the major N. gonorrhoeae Virulence Factors?

Answer 26

1) Fimbrae
- Mediate attachment to mucosal epi cells
- resistant phagocytosis

2) Ag- variation of pili structure ( rapidly changing Ag type)
- Gene conversion & Phase Variation( turn on & off gene expression)
* Escape Ab by varying Ag structure = Gene conversion (cut and paste gene)
* Reinfection possible

3) Surface receptors for host proteins (i.e cover & hide)
4) Ig A protease
5) LPS
6) Penicillin resistance (e.g B-lactamase)

Question 27

How is N. gonorhoeae transmitted ?

Answer 27

It is transmitted primarily by sexual contact.

• Women are at a greater risk 50% (due to mucosal area of women)
• Men 20%

Question 28

What is the major resevoir for gonococci?

Answer 28

• It is the asymptomatically infected person and more common in women. (Issue is that women have mild to no symptoms and men are mostly symptomatic and seek treatment).
• The infection seldom disseminates

Question 29

What occurs when women go untreated with gonorrhea?

Answer 29

10-20% develop Pelvic inflammatory disease (PID).

Question 30

What is PID?

Answer 30

• It is a chronic inflammatory response to infection (primarily N. gonorrhoeae and Chlamydia infections).
• Can result in adhesive scarring, sterility, and ectopic pregnancy.
• ***IT is the most frequent serious infection encountered by young women in the US.
• **Also the major cause of pelvic surgery in young women in the US to help elevate the symptoms of PID and to REVERSE sterility.

Question 31

What is the treatment of gonorrhea?

Answer 31

It is complicated by the ability of N. gonorrhoeae to develop resistance to antimicrobial agents. (Resistant to penicillin)

• Women are with gonorrehea are usually co infected with chlamydia so antibiotics are given for BOTH together.
• ** Vaccine is not available because of Ag- variation of bacterial epitopes.
• ** Newborns are routinely treated with anti-microbial eye ointment to prevent gonococcal eye infections which can lead to blindness.

Question 32

How does N. gonorrhoeae typically infect people?

Answer 32

It attaches to the mucosal epithelial cells, penetrating and multiplying within them. They pass thru the lamina propria where infection continues. Gonoccoci LPS stimulates a local inflammatory response that is responsible for most of the symptoms ( pyogenic lesion some oral)

Question 33

How is virulence established for N. gonorrhoeae?

Answer 33

1) Attachment factors- primarily mediated by pili
2) Avoidance of immunity factors- IgA protease, resisting phagocytosis, and Ag variation to escape Ab opsonization.
3) Causes damage to us by.. Damaging factors- ENDOTOXIN- mediated inflammation

Question 34

What is the process of infection with N. gonorrhoeae?

Answer 34

1) Enter urethra or endocervix
2) Bind microvillae of non- ciliated columnar epi
3) induce endocytosis–> coalesce phagosomes and replicate in cell/ break out into lamina propria.
4) LPS–>PMNs/ Macrophage activation–>INF..etc
kills ciliated epi cells –>Ulceration
5) Erosion releases bact. PMN cell-exudate
6) PID = scarring –> serility–>ectoptic pregnancy
7) usually N. Gon killed by C’\

Question 35

How does N. gonorrhoeae affect males?

Answer 35

-Restricted to the urethra 
disseminated infection-->sterility 
95% infected men develop acute symptoms 
-Plasma kills most N.G cell 
Rare case septicemia/endocarditis

Question 36

What does a blocked tube mean in PID?

What does a partially blocked tube mean?

Answer 36

Means the scarring in the Fallopian tube has blocked the pathway to the uterus = keeps egg and sperm from meeting

Partially blocked = keeps egg and sperm from implanting