Lecture 10 Neisseria Flashcards
What does N. Meningitidis cause?
fatal meningitis and meningococcemia ( 200,000 deaths world-wide)
What are the two major pathogenic Neisseria species ?
1) N. Meningitis 2) N. gonorrhoeae Gram-negative diplococci
How many deaths does gonorrhea cause?
650,000 and almost 300,000 cases of pelvic inflammatory disease/ yr US (stable number)
What are the characteristics of Neisseriae?
They are aerobic or microaerophilic, gram negative diplococci. They have adjacent sides being flattened together (coffee bean :)
What does both N. meningitides and N. gonorrhoeae cause?
Purulent infections, characterized by pus ( live and dead PNS, and bacteria)
Where does N. Meningitidis (meningococcus) colonize?
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)
What is meningococcemia?
Rapidly progressing bacteremia and sepsis. ( also causes a related disease by N. meningitidis)
What are the virulence factors of Major N. meningitidis
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
Why is Endemic meningococcal disease occur worldwide and epidemics common to developing countries (like sub-Saharan Africa)?
N. meningitidis is spread by respiratory droplets typically among individuals with prolonged contact (e.g family members, soldiers, students..etc)
Who are the natural carriers of N. meningitidis?
Humans are the only natural carriers of N. meningitidis and approx. 10% of individuals are asymptomatic carriers at any given time.
What are the characteristics of invasive N. meningitidis ?
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!
What are the consequences of a susceptible person that has no opsonizing Abs?
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)
What is the major window of susceptibility in children?
It occurs as maternal Ig G levels decline and their own humoral immunity is still developing.
What happens what people develop meningococcal sepsis?
- 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
What happens when people develop meningitis?
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!
What is a notable feature of N. meningitidis?
- Meningococci constantly “bleb” off large sections of their outer membrane, which contain LPS (endotoxin).
- Intense vesicle formation is a notable feature!
What is the treatment of meningococcal infections?
- 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.
How is prevention achieved for meningococcal disease?
Through 2 ways:
1) Antimicrobial prophylaxis (for those in close contact w/ carrier)
2) vaccination
What is the relatively new vaccine (2005) available?
What are its affects?
- 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)
What are the main microorganisms that cause bacterial meningitis?
1) Step. Pneum
2) H. Influenza
3) N. Meningitidis
* All have capsules
What are the viruses that cause lymphocytic meningitis?
- Mumps
- coxsackie
3) EBV
4) Polio
What are the microorganisms that cause chronic granulomatis meningitis?
1) M. Tuberculosis
2) T. Pallidum
3) cryptococcus
What are the microorganisms that cause encephalitis?
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
What are the normal hard oral species of Neisseria?
N. sica and N. perflava
What are some characteristics of N. meningitidis?
- 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.
What is the most commonly STI in the US?
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.
What are the major N. gonorrhoeae Virulence Factors?
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)
How is N. gonorhoeae transmitted ?
It is transmitted primarily by sexual contact.
- Women are at a greater risk 50% (due to mucosal area of women)
- Men 20%
What is the major resevoir for gonococci?
- 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
What occurs when women go untreated with gonorrhea?
10-20% develop Pelvic inflammatory disease (PID).
What is PID?
- 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.
What is the treatment of gonorrhea?
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.
How does N. gonorrhoeae typically infect people?
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)
How is virulence established for N. gonorrhoeae?
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
What is the process of infection with N. gonorrhoeae?
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’\
How does N. gonorrhoeae affect males?
-Restricted to the urethra disseminated infection-->sterility 95% infected men develop acute symptoms -Plasma kills most N.G cell Rare case septicemia/endocarditis
What does a blocked tube mean in PID?
What does a partially blocked tube mean?
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
