1 - Microbiology

Question 1

What are the most common causes of bacterial meningitis by age group? What are some key predisposing factors?

Answer 1

Newborn: GROUP B STREP, E. Choli, Listeria monocytogenes
Infants: NEISSERIA MENINGITIDES, H. influenzae, Strep. pneumoniae
Children: N. MENINGITIDES, Strep. pneumoniae
Adult: STREP PNEUMONIAE, N. memningitidis, mycobacteria (TB)
** Strep pneumoniae = 58% overall;
** Risk Factors: AGE, immunocompromised, basal skull fracture(entry), head trauma, surgery, cerebrospinal fluid shunt

Question 2

What are the key developmental steps of bacterial meningitis?

Answer 2

• hematogenous delivery of bacteria to SAS
• host immune response
• edema
• increased intracranial pressure
• decreased CSF flow
• cell damage, seizure, herniation

Question 3

What is a kernig’s sign? Brudzinski’s neck sign?

Answer 3

Part of diagnostic tests for bacterial meningitis.
Kernig’s sign: when supine, bending an elevated knee causes pain due to increased intracranial pressure
Brudzinski’s neck sign: when supine, bending neck(flexing) causes knees to come up towards chest
K = knee; B = bending (head)

Question 4

How is CSF evaluated for suspected meningitis? What can indicate the different pathogens?

Answer 4

Test for WBC, cell type/dominant, protein level, glucose level vs serum.
Bacterial-> HIGH WBC (>1000), mostly PMNs, some elevation protein, normal or low glucose
Viral -> low/normal WBC, mostly lymphocytes, normal protein and glucose
Fungal -> variable WBC (though associated with immunocompromised, so confounding indication), mostly lymph, elevated protein, LOW glucose
TB -> same as fungal

Question 5

What are the structural characteristics of Neisseria meningitidis?

Answer 5

• Gram(-) cocci (pairs)
• Capsule! w/ lipooligosaccharide(LOS) toxin
• chocolate agar
• oxidase (+)
• cytochrome C (reduction of dye to a blue color)
• aerobic, can multiply under microaerophilic conditions
• use sugar test to distinguish N. meningitidis from N. gonnerrhea

Question 6

What are the key virulent factors of N. meningitidis?

Answer 6

Capsule: antiphagocytic by preventing complement binding
-> capsule has 12 serogroups, Group B mimics human tissue too much to support a vaccine
LOS (lipooligosaccharide) toxin: potent toxin

Question 7

What is the typical clinical presentation of N. meningitidis?

Answer 7

1) Asymptomatic pharyngeal carrier: 5-10% population; common in closed populations (military)
2) Meningococcemia: petechiae/purpura, meningitis, chronic recurring meningococcal disease (rare), Waterhouse-Friderichsen syndrome
- >WF Syndrome: shock due to LOS, DIC, bilateral destruction of adrenal glands -> rapidly FATAL

Question 8

What are the risk groups for infection with N. meningitidis? What are the associated serogroups?

Answer 8

Non-vaccinated!: populations w/o vaccine for groups A, C, Y and W135 are MUCH more susceptible; Group A specifically epidemic in Africa
Immunocompromised
Young: 6mo-3yr (un-vaccinated)

Question 9

What is the vaccines available for N. meningitidis?

Answer 9

MCV4-> tetravalent conjugate for capsular polysaccharides from group A, C, Y and W135 (most virulent strains except B which shows too much molecular mimicry)

• > two doses for ALL 11-16y/o
• > if unvaccinated, also recommended for:
• college freshmen in dorms,
• microbiologists working with N. meningitidis
• military recruits
• travelers to non-vaccinated areas
• immunocompromised (sickle cell, asplenia, etc.)

Question 10

What are the structural characteristics of Group B strep?

Answer 10

• Gram (+) cocci (chains like Group A)
• catalase (-)
• B-hemolytic
• Bacitracin resistant
• agglutinization for group B cell wall antigen

Question 11

What is the primary method of prevention of Group B infection?

Answer 11

Most at risk are neonates during vaginal delivery from a carrier mom.
Penicillin G given i.v. to moms who are screened (+), unknown status, or pre-term.
Reduced odds of infection by 20x.

Question 12

What are the structural properties of Listeria monocytogenes?

Answer 12

• Gram (+) rod
• Aerobic
• prefers cold temps
• facultative intracellular
• listerolysin toxin (LLO) produced -> allows bacteria to escape phagosomes and survive phagocytosis
• widely found in nature and food prep (hot dogs, cold cuts, soft cheese)

Question 13

Describe the cellular pathogenesis of L. monocytogenes.

Answer 13

• Enter body via GI tract and is phagocytosed by macrophage.
• Listerolysin(LLO) toxin promotes release from phagosome, and organism multiplies within cytoplasm.
• New bacteria then migrates to new cell using a host ACTIN polymerization. Actin strip “propels” bacteria into neighboring cell cytoplasm without exiting safety of host cell.
• New cell pinches of bacteria and actin rod, and cycle repeats.

Question 14

What is the clinical presentation of L. monocytogenes infection?

Answer 14

• flu like illness
• meningitis in immunocompromised or NEWBORN
• can lead to stillborn or miscarriages in pregnant women

Question 15

Describe Poliovirus.

Answer 15

1) Poliovirus=picornavirus: non-enveloped, incosahedral structure, (+)ssRNA
2) Enterovirus-> 3 serotypes w/ very similiar properties, but no shared antigen
3) (pre-vaccine) ubiquitous human infection ( flaccid paralysis, Medulla damage-> respiratory depression/death
6) Vaccine:
- Salk-> killed bug-> used for immunosuppressed, provides Ab but no GI immunity, given in 4 doses
- Sabin-> live, attenuated(oral)-> off ALL 2 serotypes, provides Ab and mucousal IgA immunity
* * reversion to wild-type virus when using Sabin has caused push back to Salk vaccine

Question 16

Describe the characteristics and types of arboviruses significant for CNS infection.

Answer 16

1) Arboviruses are carried by insects (mosquito), have a reservoir in animals, but humans are dead-end host
2) Presentation: most are SubClinical; symptoms present 3-14d after infection and last rash, aches, chills,
- Severe: encephalitis-> ataxia, seizures, behavioral changes, optic neuritis
3) Dx: serology (ELISA), PCR
4) Types:
- Flavovirus(West Nile, St. Louis, Japanese): ELDERLY (>50) is a significant risk factor, 20% develop neuro symptoms, common in summer/fall when around birds, mosquitos or animals
- > Japanese-> prominent in east asia, but there is an effective vaccine
- Toga(alpha)virus(EEV, VEE, WEV): very rare, but very severe, potentially leading to paralysis and death, mosquito-bird cycle
- Bunyavirus(California, La Crosse): PEDIATRICS, 5-18y/o w/ 20% developing bx changes or recurrent seizures, most prevalent in midwest

Question 17

Describe Rabies infection.

Answer 17

1) Rhabdovirus: enveloped, bullet-shaped, enveloped, (-)ssRNA
2) Clinical: causes acute encephalitis which is universally FATAL if untreated; course is variable, but most are acute and 95% followed by: hyperactivity, throat spasms, hypersalvation, delirium, coma, death
3) Pathogenesis: virus infects PNS nerves and is transported (retrograde axoplasmic) to CNS via sensory/motor neurons
4) Dx: infected neurons display NEGRI BODIES-> eosinophilic cytoplasmic incusions; can also stain (direct fluoresce- dFA) for antibody in biopsy
5) Tx: VACCINE; if infected w/o vaccine-> 1) clean wound, 2) passive antibody (Human Rabies Immune Globulin), 3) vaccine

Question 18

Describe paramyxovirus infections.

Answer 18

1) Paramyxovirus-> enveloped, (-)ssRNA, SINGLE serotype
2) Mumps: infection initially of respiratory tract; ~3wk incubation period, followed by VIREMIA-> this leads to clinical presentation
- parotits, gonadal infection, ENCEPHALITIS
- Vaccine(live attenuated) provides life-long immunity(MMR)
3) Measles: HIGHLY contagious virus infects respiratory tract; ~2wk incubation period, followed by VIREMIA-> spreads to lymphoid tissue, skin, organs
- symptoms due to immune response (rash!), Koplik’s spots=blue-white bumps on inside of cheek are dx for Measles
- if unvaccinated, complications are common and severe-> acute encephalitis (~20% fatal, 40% neuro sequelae); subacute encephalitis results in CNS disease years after infection (RARE)

Question 19

Describe herpes simplex virus infection in relation to CNS infection.

Answer 19

-DNA virus
-MOST common and most severe acute encephalitis (30-70% fatal)
-Type 1-> trigeminal ganglia-> dominates
-Type 2-> sacral ganglia-> dominates in neonates (during birth)
-Symptoms tend to cluster around frontal and temporal lobe injury (hallucination, seizures, aphasia, personality changes)
Tx: acyclovir -> blocks DNA replication at thymidine kinase

Question 20

Describe CMV.

Answer 20

1) Cytomegalovirus-> herpesvirus which is a significant subclinical infection, but the MOST common cause of congenital viral infection (crosses placenta)
2) produces diffuse encephalitis with profound neurological sequelae
3) damage from virus can lead to calcification and microcephaly

Question 21

What are the characteristics of human polyomaviruses?

Answer 21

1) small, non-enveloped, circular-DNA virus that can replicate w/ or w/o integrating into host DNA
2) infections are SLOW and insidious-> tend to develop into cancers or neurological disporders
3) Merkel Cell Virus:can lead to Merkel Cell Cancer-> highly agressive cancer of elderly and immunosuppressed; thought to be acquired in childhood and then “activated” by sun/mutegens into cancer
4) JC Virus: can lead to Progressive Multifocal Encephalopathy (PML); acquired in childhood and latent in kidney, epithelium, lymphocytes, and marrow; migrates to brain and causes PML in when immunosuppressed; focal demyelinated plaques in white matter surrounded by infected oligo
5) BK virus: can lead to Tubular Interstitial Nephritis/Hemorrhagic Cystitis; acquired in childhood and latent in kidney, epithelium, lymphocytes, and marrow; migrate to GI when immunosuppressed (transplant)

Question 22

Describe Transmissible Spongiform Encephalopathies.

Answer 22

1) encephalopathy w/ dementia produced from spongiform changes of cerebrum/cerebellum w/ or w/o amyloid plaques
2) Creutzfeld-Jacob Disease: elderly, familial and iotragenic patterns of infection; via mink/deer/elk; develops into Chronic Wasting Disease
- >variant CJD seen in UK: neuropsychiatric disease of young adults (20-300; progresses to dementia; associated with Dense Amyloid Plaques; Genetic-> PrP genotype
3) Familial/ GSSS: progress to Spongiform Encephalopathy (Mad Cow); associated w/ cow, feline, exotic animals; presents w/ amyloid plaques similar to vCJD

Question 23

What are the two main theories of pathogenesis of transmissible spongiform encephalopathies?

Answer 23

1) Pruisner’s Prior Hyp: protease resistant prion protein (PrP-Res) that forms amyloid is the infectious agent; induces normal PrP to fold abnormally and form amyloid (nucleation)
2) Menuelidis Rational: infectious cause is actually a small, circular virus yet unidentified; explains why there is more phenotypic specificity with the strain of infection than the host