13_Haemophilus influenzae Neisseria meningitidis, Neisseria gonorrhoeae

Question 1

hemophilus influenzae

1. what type causes meningitius?
2. carriers/ transmission?
3. gram neg or pos?
4. shape?

Answer 1

1. type B
2. carried in human nasopharynx by healthy people; transmitted by aerosol droplets
3. gram negative
4. coccobacilli

Question 2

what is meant by Haemophilus influenzae being pleomorphic?

Answer 2

the ability of some micro-organisms to alter their shape or size in response to environmental conditions

Question 3

what conditions can result from nontypable strains of haemophilus influenzae?

Answer 3

Unencapsulated strains are termed nontypable (NTHi) because they lack capsular serotypes; these types cause:

• Otitis media
• Sinusitis
• Chronic bronchitis

Question 4

pathogenesis of haemophilus influenzae:

1. # of serotypes based on capsules
2. which type causes bacteremia, meningitis, and epiglottitis?
3. which strains have a capsule? what is this capsule called?

Answer 4

1. 6 Serotypes based on capsules; designated by letters “a” to “f”
2. ONLY TYPE B can be invasive, causing bacteremia, meningitis, and epiglottitiis
3. TYPE B strains have a capsule; Capsule is PolyRibosylribitol Phosphate (PRP)

Question 5

relationship between incidence of H. influenzae meningitis during first 5 years of life, an dthe levels of type B capsular polysaccharide antibodies?

Answer 5

As incidence decreases, the number of H.i.b. (anti-H. influenzae type B capsular polysaccharide antibodies) increases

• inversely related

Question 6

H. influenzae vaccine:

1. structure
2. antibody responsiveness?
3. what happens when antibodies react to capsule?

Answer 6

1. Purified PRP polysaccharide covalently complexed
   to a protein carrier

2. Purified PRP **_does not induce antibody responses in
 children \< 2 years_**. The conjugate vaccine is effective
 in infants (*the protein carrier converts the T-independent polysaccharide to a T-dependent antigen)*

3. Antibodies to capsule promote phagocytosis directly and by complement fixation

Question 7

effects of vaccines on incidence of H. influenzae

Answer 7

Vaccine efficacy eliminates incidence of H. influenzae type B

(decreases occurrence to near 0)

Question 8

what are the different types of Haemophilus vaccines?

Answer 8

monovalent vaccine

combination vaccine

Question 9

Haemophilus influenzae:

diagnosis?

treatment?

Answer 9

• diagnosis
  
  • Requires 2 factors not found in blood agar to grow:
    
    • X factor: hematin (hemin)
    • V factor: NAD (nicotinamide adenine dinucleotide)
  • Grow on chocolate agar, w/ lysed RBCs plus hematin and NAD;
  • Fastidious: grows best in increased CO2
• treatment
  
  • third generation cephalosporins

Question 10

Which is the best answer with regard to Haemophilus influenzae?

1. Causes influenza
2. Frequently infects young adults
3. There is no vaccine
4. Protection is by antibody

Answer 10

Protection is by antibody

Question 11

other name for neisseria meningitidis?

other name for neisseria gonorrhoeae?

are both: gram negative or positive? what is shape?

Answer 11

• neisseria meningitidis –> meningococcus
• neisseria gonorrhoeae –> gonoccocus

Both are GRAM NEGATIVE DIPLOCOCCI

Question 12

what is this gram stain of?

Answer 12

meningococcal meningitis

(cerebral spinal fluid (CSF) gram stain)

Question 13

What are the key symptoms of Neisseria meningitidis?

Answer 13

• Stiff neck, abrupt onset of fever, hypotension, purpura, thrombocytopenia and petechial rash

Question 14

What condition (with of the same symptoms EXCEPT STIFF NECK) presents similarly to Neisseria meningitidis?

Answer 14

Sepsis and septic shock

(Sxs: brupt onset of fever, hypotension, purpura, thrombocytopenia and petechial rash)

Question 15

What are the top 3 clinical manifestations of Neisseria meningitidis?

Answer 15

• *Meningitis: 47.3%
• Bacteremia: 43.3%
• Pneumonia: 6.0%

Question 16

N. meningitidis: epidemiology

1. carriers
2. transmission
3. incidence/ mortality

Answer 16

1. ONLY HUMAN HOST; carried in nasopharyngeal flora of 10% of healthy people
2. Tx: by inhalation of respiratory droplets
3. 349 cases in 2017 in US; case fatality is 10-15% depending on group

Question 17

Where were the 2 major outbreaks of Meningitis?

Answer 17

• Nigeria: 14,518 suspected cases, 8% fatality
• Northern Ghana: 133 cases serogroup W

Question 18

What are the virulence factors of Neisseria?

Answer 18

• Capsules are Neisseria virulence factors
• Neisseria meningitidis virulent strains are encapsulated
• CAPSULES ARE ANTI-PHAGOCYTIC;
  
  • can be shed into blood or lymph to bind up antibodies, acts like a decoy, using up the antibodies ineffectively

Question 19

N. meningitidis pathogenesis:

1. how do they attach?
2. travel to..
3. if progresses to meningitis?
4. what is found in the membrane?

Answer 19

1. attach by pili to nonciliated epithelia of naspharynx
2. penetrate through cells and invade blood stream
3. if progresses to meningitis, then crosses the blood-brain barrier and invade the meninges
4. LOS(lipooligosaccharide), a form of lipopolysacchride is found in the membrane

Question 20

What is LOS and what can it affect?

Answer 20

• LOS(lipooligosaccharide), a form of lipopolysacchride is found in the membrane; a truncated lipopolysaccharide
• Release of LOS is toxic and causes endotoxic shock

Question 21

N. meningitidis virulence factors:

purpose

Answer 21

Neisseria fights via several virulence factors to stay and multiply extracellularly

Question 22

Antibody to capsule alone is protective:

evidence?

Answer 22

1. Shows that Ab levels correlate w/ protection
2. Shows that passive antibody (polyclonal or monoclonal) alone confers protection in rodents
3. shows that vaccination with purified capsule is protective

Question 23

What are the vaccines available for Meningococcal disease?

Answer 23

1. 2 quadravalent conjugate vaccines are licensed in the US; these vaccines are composed of the capsular polysaccharides of serogroups A, C, W-135, and Y linked to diphtheria toxoid or to a mutated, inactive diphtheria toxin as a carrier (carrier is T-dependent)
2. Two new vaccinres for serogroup B were licensed in 2014 and 2015

Question 24

What features/tests do you look for to diagnosis N. meningitidis in the lab?

Answer 24

• Features:
  
  • Kidney-bean shaped Gram negative diplococci
  • Neutrophils in CSF
• Tests: Nucleic acid amplification tests
  
  • Or test for antigen in CSF using latex agglutination

Question 25

Treatment for N. meningitidis

Answer 25

* 3rd generation cephalosporins: Cephtriaxone or cefotaxime (or penicillin) * Case contact prophylaxis uses rifampin, ciprofloxacin, or ceftriaxone

Question 26

Neisseria diplococci: shape?

Answer 26

* Kidney bean shape

Question 27

**Neisseria gonorrhoeae:** gram stain, nickname, disease

Answer 27

* Gram negative diplococci * Called GC (as abbreviation for **_G_**ono**_c_**occus) * Disease: Gonorrhea; also called the Clap (clapoire)

Question 28

Neisseria Gonorrhoeae: 1. transmission, 2. symptoms 3. treatment

Answer 28

1. Sexually transmitted (STI - sexually transmitted infection, or STD - sexually transmitted disease) - human to himan * **\*Asymptomatic carriage (esp by females), provides a reservoir of organisms that can be transmitted to sex partners** 2. Symptoms * Males - painful urination w/ purulent pus; exudate shows **intracellular diplococci in neutrophils** on microscopy * Females - **\*30% are asymptomatic;** can see pain on urination, vaginal discharge, abdominal pain 3. Tx: if no tx, can resolve in several weeks in med

Question 29

**Neisseria gonorrhoeae:** pathogenesis

Answer 29

1. **Lipooligosaccharide (LOS)** is found in outer membrane --\> has endotoxic activity; 2. Attachments: * **Pili** * **Opa proteins -** outer membrane proteins; opa=opacity, for change in colony appearance 3. **Invasion**: pathogen-directed endocytosis into nonciliated epithelial cells; attachment by pili and Opa proteins 4. Organisms USUALLY stay localized in mucosal tissue, but occasionally can get **disseminated gonococcal infection (DGI);** or gonococcal arthritis (where organisms lodge in a joint like elbows or knees)

Question 30

what modification to LOS can block complement activation?

Answer 30

polysaccharide has sialic acid residues; **Sialylated LOS** blocks complement activation

Question 31

Neisseria gonorrhoeae: evasion of host responses

Answer 31

1. \***Antigenic variation (**even in a single host) * pili variation, and opa variation 2. **Survival in phagocytes (neutrophil PMNs)** * Gonococci make **catalase** which interferes w/ peroxide-mediated killing mechanisms inside of PMNs (phagocytes) 3. Sialylated LOS blocks complement activation

Question 32

Why is there no vaccine for **Neisseria gonorrhoeae?**

Answer 32

There are too many antigenic variants; Pilus vaccines were tried and failed

Question 33

**Neisseria gonorrhoeae:** clinical manifestations

Answer 33

1. Men: urethral strictures, epididymitis, prostatitis 2. Women: **PID (pelvic inflammatory disease)**; fallopian tube inflammation w/ scarring, strictures, pelvic pain, ectoptic pregnancy * **women are most at risk bc the disease is more frequently asymptomatic** in women --\> as such, consequence goes untreated 3. Both sexes can have disseminated gonococcal infections: arthritis, (rareles meningitis)

Question 34

**Neisseria gonorrhoeae:** 1. diagnosis 2. culture

Answer 34

1. diagnosis: * men: visualization of intracellular diplococci in smear of urethral exudate (presumptive diagnosis) * women: must do cultures to establish diagnosis; **\*cervical** or rectal swabs 2. culture: * **Gonococci are fastidious and fragile** * Grow on chocolate agar * For urogenital, anal, or throat swabs, use **Thayer-martin** or **Martin-Lewis agar** (which is cholocate agar + Abx that inhibit other normal flora) * **Nucleic acid amplification tests (NAAT)**

Question 35

Neisseria gonorrhoeae: treatment

Answer 35

* **Injectable ceftriaxone in combination with oral azithromycin or doxycycline are current drugs of choice. Increasing antibiotic resistance a problem.** * **%30% of patients with GC are co- infected with Chlamydia.**

Question 36

In comparing N. gonorrheae and N. meningitidis, pick the one true statement: 1. N. gonorrheae is transmitted by sheep, but N. meningitidis only infects humans. 2. Both of these organisms usually become systemic. 3. Both organisms grow as diplococci. 4. Neither organism has a capsule.

Answer 36

* \*Both organisms grow as diplococci

Question 37

What are the similarities and differences of Neisseria Gonorrheae and Neisseria Meningitidis?

Answer 37

Key Differences: * N. gonorrhoeae -- carried by asymptomatic females/ recovering males * No capsule * Usually loalized Wherease **N. meningitidis - nasopharynx - capsule - systemic disease**