Bacterial infection CNS Flashcards
Meninges
Three membranes enclosing the brain and the spinal cord, comprising the dura mater, the pia mater, and the arachnoid membrane.
The _____and _____ can become inflamed during bacterial meningitis, causing complications that may be life-threatening.
pia mater and the arachnoid
Primary pathogens in bacterial meningitis
Group B Streptococcus (baby)
Streptococcus pneumoniae
Neisseria meningitidis (teens/college)
Haemophilus influenza (unvaccinated)
Occasional pathogens seen in bacterial meningitis
Occasional pathogens
Listeria monocytogenes (> 50 years of age)
Escherichia coli and other Enterobacteriaceae
Staphylococcus aureus
Nocardia
Mycobacterium tuberculosis (AIDS associated)
Borrelia burgdorferi, Leptospira , Treponema pallidum
Brucella
Brain damage during meningitis is mostly attributable to :
Bacteria like Streptococcus pneumoniae activate ______ that release proteolytic enzymes and reactive oxygen species that can damage host tissue
the side effects of the host’s own inflammatory response.
leucocytes
Early signs on bacterial meningitis
Problem, early signs of meningitis can resemble the symptoms of influenza (fever, distinct and severe headache, stiff neck, nausea, vomiting, photophobia (light sensitivity) or analtered mental status (confusion).
**Key: rapid diagnosis. **
Premature babies and newborns up to three months old get what kind of bacterial meningitis
group B streptococci (inhabit the vagina and are mainly a cause during the first week of life)
Escherichia coli that normally inhabit the digestive tract and carry the K1 antigen
Listeria monocytogenes
Older children commonly get what kind of bacterial meningitis
Streptococcus pneumoniae and Neisseria meningitidis
Haemophilus influenzae type B (HiB, in countries that do not vaccinate)
Adults are most susceptible to what kinds of bacterial meningitis
Streptococcus pneumoniae and Neisseria meningitidis together cause 80% of bacterial meningitis cases.
Listeria monocytogenes is a risk in the elderly > 50 years.
Group B Streptococcus (agalactiae) (G+)
Has a capsule:
Has a vaccine:
What do you tx it with?
Yes
No
Neonatal sepsis–>meningitis Antibiotic therapy (Beta-lactams)
Streptococcus pneumoniae (G+)
Has a capsule:
Has a vaccine:
How do you identify it?
Yes
Yes
Responsible for most pneumonia and see Meningitis diplococcus identified in the CSF
Neisseria meningitidis (G-)
Has a capsule:
Has a vaccine:
What’s an issue with the vaccine?
Yes
YEs
Conjugate vaccine does not protect against serotype B, a di-sialic acid homopolymer similar to human structure
Most capsules are composed of________
Anti-capsule antibodies prevent ______
polysaccharides
host cell phagocytosis
Most common meningits causing pathogen worldwide
Gram negative Haemophilus influenzae.
(left) Small coccobacilli forms seen in sputum.
(right) Thin, pleomorphic forms seen in a 1-year-old unvaccinated child in Africa with overwhelming meningitis.
Capsular polysaccharide of Haemophilus influenzae that is the one we worry about
Serov B: has ribose and ribotol
Immunity to Hib
- Good relationship between age & susceptibility
- Children < 3 month, ______are protective
- Most invasive disease occurs between________
maternal Abs
3 month and 3 years of age
humoral immunodeficiency
- Children under 3 years of age show a ________ to Hib
- Children older than 3 years of age develop ________
humoral immunodeficiency
bactericidal Ig to Hib (vaccination/non-clinical exposure)
1st generation Hib vaccine
–Purified capsular polysaccharide of Hib was licensed for immunization (PRP) (1985)
- 90% effective in children ________
- ineffective in children ______
>24 months
<18 months
Problem with 1st gen HIb vaccine
*Problem, Polysaccharides are:
1) poor immunogens
2) stimulate T-independent Ab
3) poor immunologic memory
Describe 2nd generation Hib Vaccine
PRP protein conjugates
has diptheria toxoid as the protein carrier
with vaccine tehre is limited clincal concern
Polysaccharide conjugate vaccines stimulate a ____ response and memory response
T-Cell dependent antibody response and memory response
Explain difference between polycaccharide only and conjugate vaccine for Hib
Polysac will result in no production of memory B cells; we get IgM to Hib but no memory cells
In Conjugate we get both IgM and IgG response; get this very robust response
is Gram negative diplococci and is an intracellular, human-specific pathogen responsible for septicemia and meningitis.
Neisseria meningitidis (Nm)
What are the 3 virulence factors in Neisseria meningitis
Lipooligosaccharide: component of the outer membrane (endotoxin) which stimulated TLR system to produce: fever, septic shock, and hemorrhage due to the destruction of red blood cells
Polysaccharide capsule: prevents host phagocytosis and evasion of host immune response
Fimbriae which mediate attachment of the bacterium to cells of the nasopharynx.
What is the gold standard to diagnose N.Meningitidis
• Gold standard is to isolate Nm as Gram negative diplococci from cerebrospinal
fluid (CSF)
• Culture CFS on chocolate agar plate
• Polymerase chain reaction (PCR) may also be sued to identify Nm
Pathology of N.meningitis
- Fatality risk approaches 15% within 12 hours of infection, so initiate testing as quickly as possible, but :
- Persons with confirmed Nm infection should be :
do not to wait for the results before initiating antibiotic therapy.
hospitalized immediately for treatment with antibiotics
What is done to prevent N.Meningitis
• Nm can be transmitted, so contacts of the infected patient over the 7 days before onset should receive antibiotics to prevent secondary infections, especially young children.
• ~1,000 people get meningococcal disease each year in the U.S. Even when treated with antibiotics, 10–15% of these people die.
It is most common in:
infants < one year and 16–21 years.
• Children with certain medical conditions, such as lack of a spleen, have increased risk of getting meningococcal disease.
• College students living in dorms are at increased risk (exposure).
While N.Men has 13 serogroups the vaccine targets:
6 serogroups (A, B, C, Y, W135 and X) are responsible for virtually all cases in humans.
is the preferred vaccine for people 55 years of age and younger.
Meningococcal conjugate vaccine (MCV4)
has been available since the 1970s. It is the only meningococcal vaccine licensed for **people older than 55 (elderly) **
Meningococcal polysaccharide vaccine (MPSV4)
(1) β-hemolytic streptococci are classified by _______
(2) α-hemolytic and γ-hemolytic streptococci, which are classified by biochemical testing,
_______ are referred to as viridans streptococci, derived from viridis (Latin for “green”), referring to the green pigment formed by the partial hemolysis of blood agar.
Lancefield grouping
a-hemolytic=green
Classification of the streptococci
• Hemolysis when grown on blood agar plates measure lysis of blood cells
______ (complete lysis)
______ (partial lysis)
_______(no lysis)
b clear (complete lysis)
a green (partial lysis)
g none (no lysis)
Descibe the lancifield classification that is based on cell wall components
Group A = Strep.Pyogennes (b hemolytic)
Group B = Strep.aglatiae (B hemolytic)
S. Pneumoniae = no lancefiled (aplha hemolytic)
Elongated gram-positive cocci arranged in pairs (diplococci) and short chains
Streptococcus pneumoniae
Key virulence factors in s. pneumonaie
Ability to colonize oropharynx (surface protein adhesions)
Spread into normally sterile tissues pneumolysin, IgA protease)
Stimulate TLR inflammatory response (teichoic acid, peptidoglycan fragments),
Evade phagocytic killing (polysaccharide capsule)
Disease caused by Strep. pneumonaie
• Responsible for pneumonia, sinusitis and otitis media, meningitis, and bacteremia
Vaccine for Pneumococcus for children under 2 or Children 6 through 18 and older
• PCV13 is given to infants as a series of 4 doses, one dose at each of these ages: 2 months, 4 months, 6 months, and 12 through 15 months.
Infants and Children younger than 2 Years of Age
Gram positive, beta-hemolytic
Lancefield typing scheme Group B
Common inhabitant of pharynx, vagina neonatal infections, meningitis
Group B streptococcus, Streptococcus agalactiae
Pneumococcal vaccine for 65 and older
Vaccinate with PPSV23 vaccin
2 pneumococcal vaccines:
pneumococcal conjugate vaccine _____
pneumococcal polysaccharide vaccine _____
(PCV13)
(PPSV23).
What happens to neonates that get infected with Group B strep?
neonatal infections, meningitis
– mortality in full-term infants = 2-8%, while in pre-term infants may rise to 30% mortality
Tx for newborns with group B strep
No licensed vaccine
Penicillin is the drug of choice as a therapy
• Selective prophylaxis antibiotics for Group Bstreptococcus
Pre-term infants
Early membrane rupture (Infection and inflammation)
Previous infant with Group B streptococcal disease
Rabies: (Latin for “madness”) has been present in human populations throughout recorded times and probably predates evolution of humans.
– A common cause of death in developing world, but rare in US and developed countries (why would that be?) – annual costs in US associated with post-exposure prophylaxis (PEP) for suspected exposures is significant
boring info on rabies
how does rabies replicate?
Replication: is the prototype for (-) sense RNA viruses
Rabies: There is one viral serotype, but several ‘strains’ from different animal species and locations can be identified due to genetic variation – these can be distinguished by
monoclonal antibodies or sequence information such that is possible to determine if a human was infected by a dog, bat, etc., rabies virus
Rabies: The _____elicits neutralizing antibodies, but natural ‘timing’ of antibody production is not protective.
“Fixing” (primitive inactivation) of virus from rabbit brain yielded the ‘vaccine’ of Pasteur. ___________ allows for vaccine production
G glycoprotein
Antigenicity of G protein
Entry and invasion features of rabies
a. entry is usually through a wound or skin abrasion via s bite and introduction infected saliva
– one report of “aerosol” infection in cave explorers
– can be transmitted by infected cornea transplants, and more recently from organ transplants !!
i) “furious” or fulminant – classic rabies presents with:
with bizarre behavior; hallucinations; seizures; ‘hydrophobia’, which is violent spasms of respiratory muscles triggered by drinking water: sight, sound, or mention of water can trigger it.
**– ‘fury’ gives way to paralysis, then either coma or sudden fatal cardiac or respiratory arres
How do we tx people exposed to rabies?
Post-exposure Prophylaxis (PEP, ~20,000/yr in US).
Almost always effective if incubation period is long enough, which is almost always the case. Thus, although an exposure is not a medical dFA emergency, **PEP should be initiated as soon as possible after exposure **
Passive vs active immunization for rabies
ii. passive immunization – human or equine rabies immune globulin (HRIG/ERIG) introduced into wound area and intramuscularly to provide Ab until immunization becomes effective: keeps virus ‘local’
iii. active immunization – human diploid cell vaccine of “killed virus”. 2010 recommendation: 4 doses at 0,3,7, and 14d, post-exposure (used to be 5 doses, but shortage of vaccine in 2009 necessitated 4 dose, which proved effective
Rabies is almost always fatal once _____
symptoms appear
*in 2004, the FIRST case of survival where NO immunotherapy intervention was initiated …. this success story happened at our Children’s Hospital of Wisconsin, with Dr. Rodney Willoughby as the lead physician.
Describe Dr. Willoughbys rabies tx results
reatment based on observations that at death:
i) patient’s brains are ‘normal’, no gross pathology to explain devastating consequences of disease…
ii) there are antibodies during the final acute phase, as if the body mounted an immune response, but just too late…
iii) and, there is often little virus remaining, especially in those who have a prolonged acute phase, showing that the immune response can eradicate the virus…
Dr. Willoughby suspected that rabies is a _________ Treatment was based on premise that if one could protect the brain long enough (through therapeutic coma)
for immune system to eradiate virus, the brain would be spared. It worked !!! And has worked 4 additional times (with many failures), most recently in 2011 in an 8-yr-old CA girl.
metabolic disease (a disease of ‘software’, not ‘hardware’).
LP results:
CSF: WBC = 50-100
Predominant celsl = mononulcear
glucos = normal
protein = <200
Viral meningitis
LP results:
CSF WBC: 200-500
predominant cells = neutrophils
gluocse = low
protein = 100-500
Bacterila meningitis
LP results
CSF WBC = 50-300
Predominant cells = mononulcear
Glucose = low
protein = 50-300
TB meningitis
LP results
CSF WBC = 0-500
Predom cells = mononuclear
glucose = low
>50 protein
Crypto meningitis
Most common organisms for all meningitis
Streptococcus pneumo
Alcholics are at risk for what type of meningitis?
Listeria(also seenin babies or immuncompromise)
PT that has recent brain surgery is most at risk for what causitive organism causing meningitis?
staph
What tx do you provide to pt with TB meningitis
PO rifamipin, isoniazid, pyrasinamide, ethambutol and coritocosteroids
What meds would you start on pt you suspect has bacterial meningitis?
Empiric therapy:
IV ceftriaxone, vancomycin, corticosteroids
What can be done to prevent bacterial meningitis?
vaccine for pneumo, menigococcs and H.flu
What would we do for old pt with meningitis from listeria?
Add ampicillin; as well as the IV ceftrixone, vancomycin, corticosteriods
Have 62 yo female acting crazy for few months; has auditory hallucinations and bizzare behavior for past few days. Afebrile, no stiff neck. She is arousable, but disorientd and uncooperative. No focal neuro deficiets, no PMHx, no meds
What is most important microbiologicl etiology to consider?
HSV1: because it’s curable!!!!
get imaging and LP
See temporal lobe enhancement on CT
CSF shows 97 WBC
88% lymps
glucose 66 and protein 79
points to Herpes
start on acyclovir
