Title: T4 / BV6 / Modul 5 / Bakteriella CNS infektioner

Q: How can neisseria meningitidis be summarized?
A: - Common coloniser of the nasopharynx
- Invasive meningococcal disease
- Meningitis and septiaemia
- Asymtomatic carrier - 15-40%
- High mortality rate
- Vaccine exists

Q: How can neisseria gonorrhoea be summarized?
A: - Sexually transmitted disease (gonorrhea)
- Antibiotic resistant
- Increasing transmission rate
- Complications - infertility to cardiac problem
- No vaccine

Q: How many cases of gonorrhoea were reported in swe 2021, and how many were AR?
A: - 2700 reported cases
- 1583 - antibiotic resistant (59%)

Q: What are the neisserial virulence genes?
A: - Capsule (not N. gonorrhoea)
- LPS
- Factor H binding protein
- Pili (adhesion)
- Receptors that bind human transferrin and lactoferrin
- The production of IgA protease
- Nutrient scavenging mechanisms

Q: What can be seen in the eyes of someone with n. gonorrhoea?
A: - Gonococcal conjunctivitis in adults is usually seen in people with genital gonorrhea
- Opthalmia neonatorum - neonatal ocular prophylaxix with topical antibiotics or 1% silver nitrate

Q: What do gonorrhoea have connected to conjuctival epithelium?
A: Has special "processes" allowing them to attach to the conjunctival epithelium

Q: What is the neisserial typ IV pilus used for?
A: Major virulence factor:
- Adhesion
- Aggregation
- DNA uptake

Q: How can the pilus of gonorrhoea be used in antigen variation?
A: Non-reciprocal recombination of PilE antigenetic variation

Q: What is meningititis?
A: Inflammation of the meninges

Q: Which types of meningitis exist, species?
A: - Bacterial
- Aseptic ( absence of infectious agent)
- Viral, mycoplasma, fungal, spirochetes: syfilis, Lyme
- Protozoa: malaria
- Malignancy
- Lupus erythematous
- Lead or mercury poisoning
- Drug-induced aseptic meningitis
- Postoperative

Q: CSF, production, volume?
A: - Produced by plexus choroideus, which also controls the constituency of CSF
- CSF volume varies by age with a normal adult having a steady state volume of ca. 150 ml
- CSF is reabsorbed in the venous sinus system
- Adult produces ca 500 ml a day
- STERILE

Q: Is CSF sterile?
A: Yes

Q: What bacterial pathogens cause meningitis with intact mechanical barriers?
A: - S. pneumoniae
- N. meningitidis
- H. influenzae (type B or Hib)
- L. monocytogenes

Q: What bacterial pathogens cause meningitis with traumatic alteration or other risk factors?
A: - B. burgdorferi
- S. aureus
- E. coli
- P. aeroginosa

Which symtomes of meningitis can be seen?

Q: Which pathogens can cause meningitis?
A: - Bacteria, viruses, fungi, parasites, or toxins
- Bacterial has a 25% mortality in adults

Q: What is infected in bacterial meningitis?
A: Infection of the pia mater and arachnoid, the subarachnoid space, the ventricular system, and the CSF

Q: What is the pathogenesis behind bacterial meningitis, how does bacteria enter the brain?
A: - Upper respiratory infection - blood borne - CNS entry
- Inflammatory response by meninges, CSF, ventricles
- Neutrophils migrate producing exudate that plugs off CSF flow around brain and spinal cord

Q: How does meningitis develop when in the brain?
A: Once in CSF, the absence of antibodies and complement components allows bacterial infection to flourish
Cascade of events:
---> Cell wall and membrane products of organism disrupt capillary endothelium of CNS (BBB)
---> Margination and transmigration of polymorphonuclear leukocytes (PMNs) across endothelia in CSF ---> Release of cytokines and chemokines into the CNS
---> Inflammation of subarachnoidal space

Q: What cascade of events take place as bacteria enter the brain?
A: - Cell wall and membrane products of organism disrupt capillary endothelium of CNS (BBB)
- Margination and transmigration og polymorphonuclear leukocytes (PMNs) across endothelia in CSF -> release of cytokines and chemokines into the CNS
- Inflammation of subarachnoidal space

Q: How dangerous is bacterial meningitis?
A: - Mortality up to 70% (depending on pathogens)
- Neurologic sequele: 10-15% of surviving patients

Q: When is sRNA produced (in response to)?
A: 1. Nutritional depravation(stalling of ribosome, uncharged tRNA)
2. Temperature (thermosensors)
3. pH
4. Small molecule ligands (riboswitches)

Q: How does n. gonorrhoea respod to antibiotics?
A: Heavily antibiotic resistant

Q: In what age is gonorrhoea most prevalent?
A: - Women: 20-24
- Men: 20-24 & 25-43

Q: What do gonorrhoea have to fight antibiotics
A: MTR-pumps that pump out B-lactams

Q: How does the function of pili on gonorrhoea vary with amount expressed?
A: Through homologous combination the bacteria can recombine to form a new pili
- The bacteria can change quickly (pilus) so the immune system wont detect it
- Sometime sthe bacterium priduce 1 pilus, for DNA upptake
- 2 pilus - aggregation and adhesion
- More pili on surface are involve din the response to our immune system

Q: WHich are the most important virulence factors of gonorrhoea?
A: - OpA - recognized ceacam-rec
- Pili (4?)

Q: What are ex of human adapted nasopharyngeal pathogens (causing CNS infections)?
A: - N. meningitidis
- S. pneumoniae
- H. Influenzae

Q: How can n. meningitidis be described?
A: - Gram-
- Aerobic
- Diplococcus
- Aerosol-borne pathogen

Q: How are petechiaes formed from neisseria?
A: Clots form around the bacteria and blocks the vessels causing petichies

Q: What does n. meningitidis cause?
A: - Meningitis
- Septicaemia

Q: Where does n. meningitidis reside and where can it be found?
A: - Resides at the epithelial mucosal surface of the human nasopharynx
- Usually found in asymtomatic carriers with the prevalence of 10-40%

Q: How dangerous is n. meningitis (serogroups)?
A: - Mortality rate is 10-15% -> sequele such as hearing loss, neurologic and brain damage
- Twelve serogroups have been identifies, 5 of which cause epidemics

Q: What is crucial for n. meningitis survival?
A: Fine-tuning expression of virulence factors is cruical for n. survival

Q: How does n. meningitidis enter the brain?
A: Damage to epithelial/endothelial cells which allows for the bacteria to be transported in

Q: WHich virulence factors does n. meningitidis have?
A: - Capsule
- LPS
- Factor H-binding protein
- Pili
- Receptors for transferrin and lactoferrin

Q: WHich 2 bacteria can be found in the pharynx that cause CNS infections?
A: - S. pneumoniae
- H. influenzae

Q: What facilitates s. pneumonia and h. influenzae immune evasion?
A: - RNA thermosensors
- Capsule biosyntesis factors are thermoregulated
- Factor H bidning proteins are thermoregulated

Q: How is immune evasion triggered in nasopharyngeal pathoegns?
A: Immune evasion is triggered by temperture

Q: What does the incidence look like for pneumococcus and haemophilus?
A: Pneumococcus - it declined during corona but is now increasing again
Haemophilus - old people get it, reduced incidence during the pandemic

Q: WHen does pnenumoccus and haemophilus produce more capsule adn factor H binding proteins (fHbp)?
A: In warmer temperatures

Q: What are ex. of spirochaetales?
A: - Treponema
- Borrelia
- Leptospira

Q: How can the periplasmic flagella differ between spirochetes?
A: - Differing number sof periplasmatic flagella according to genus and species
- May overlap at center of cell in treponema and borrelia but not in leptospira

Q: Which formations can borrelia cause?
A: Rosette formations, looks like malaria which do the same

Q: What is borreliosis associeted with?
A: "Poverty and crowding" and summer

Q: HOw is louse-borne borreliosis (epidemic relapsing fever) transmitted and what does it cause?
A: - Transmitted person-to-person by human body lice from infected human reservoir
- Infect host inly when louse is injured, e.g. during scratching
- A single louse can only infect a single person
- Lice leave host that develops a fever and seek a normal temperature host

Q: How is tick-borne borreliosis (endemic relapsing fever) transmitted and what does it cause?
A: - Sporadic cases
- Transmitted by ticks from small mammal reservoirs
- Ticks can muktiply and infect new human hosts

Q: WHat is the lifte cycle (transmission) of borrelia?
A: Borrelia transmitted into guts of ticks, goes from original host to a 2nd host, i sve it's often birds, if one is bitten by one of these nymphs one might get it, after biting, it will become female and lay eggs and the cycle restarts

Q: What is the pathogenesis of relapsing fever?
A: - Acute infection with 2-14 days (ca 6 day) incubation period
- Followed by recurring febrile episodes
- Constant spirochaetemia that worsens during febrile stages

Q: How does the risk of getting lyme borreliosis increase?
A: The longer the tick stays the higher the chance of getting infected

Q: Which 3 stages is lyme disease characterized by?
A: - Initially erythema chronicum migrans (ECM) with gene malaise and flu-like symtomes (only in 50% of infected cases, can reoccur periodically)
- Subsequent stage: 5-15% of patients with neurological or cardiac involvement
- Third stage: migrating episodes of non-destructive, but painful arthritis

Q: What happens in the initial phase of lyme disease?
A: - Initially erythema chronicum migrans (ECM) with gene malaise and flu-like symtomes (only in 50% of infected cases, can reoccur periodically)

Q: What can untreated borreliosis (lyme) lead to?
A: Bell's palsy

Q: How is lyme borreliosis treated?
A: Penicillin-V (kåvepenin) or tetracycline

Q: What does borrelia evade?
A: Evades complement mediated killing

Q: What does borrelia form?
A: Biofilm

Q: Which virulence factors does borrelia have?
A: - Immune evasion
- Antigenetic variation
- VIsE

Q: What are some other virulence factors of borrelia?
A: - Immune evasion
- Tissue colonization
- Dissemination (heart and joints, stay there as biofilm)
- Plasminogen recruitment
- Proteases
- Vascular transmigration

Q: How is lyme diagnosed?
A: Serology

Q: What is ex of a bacteria causing meningitis that enters the body through the GI?
A: Listeria moncytogenes

Q: What does listeria monocytogenes look like?
A: - Gram+
- Rod-shaped
- Non-sporulating bacterium

Q: Who is susceptible to listeria monocytogenes?
A: - Widespread in nature, infections of the population are rare but it may cause life threatening infections (bactereamia, meningoencephalitis)
- Susceptible groups (Young, Old, Pregnant and Immunocomprimised = YOPI)

Q: How dangerous is listeria?
A: - Mortality highest in infants of septic mothers/the severly immunocomprimised
- Meningitis mortality is very high, because it's not detected until the final stage

Listeria in sve?

Q: What is the pathophysiology of a listeria infection?
A: Ingest contaminated food, listeria goes into te blood -> liver -> grows -> released back into the blood -> can go to te brain and cross the placental barrier

Q: 2 important virulence factors (surface invasins) of listeria?
A: - InIA (recognized E-cadherin)
- InIB (recognized C-met)
Helps enter cells

Q: In which cell does listeria grow?
A: Listeria can grow inside macrophages, they cant kill the bacteria, and the lifte cycle of listeria can happen in them