1. Bacterial Meningitis=Strep pneumoniae, H. influenzae type b, Neisseria meningitidis

2. Neonatal meningitis=Strep agalactiae, E. coli, Listeria monocytogenes

3. Tetanus=Colstridium tetani

4. Botulism=Clostridium botulinum

5. Tuberculoid Leprosy=Mycobacterium leprae

6. Lepromatous Leprosy=

Discussion Questions:

What pathogen caused the outbreak of meningitis in Michigan?

What are the key features of this disease that indicate it is meningitis and not simply a case of the “flu”?

How was the disease transmitted in these settings?

Why is it important to quickly identify close contacts of those who come down with meningitis?

What are the other common causes of bacterial meningitis?

Bacterial Meningitis

symptoms in adults

sudden fever

severe headache

stiff neck

nausea, vomiting, confusion, SEIZURES, photophobia, flu-like symptoms

rashes--meningococcal meningitis (Neisseria)

Bacterial Meningitis

clinical symptoms in newborns/children

constant crying

poor feeding 

sleeping constantly

irritability

Strep pnuemoniae

diseases it causes

MOPS

Meningitis

Otitis Media

Pneumonia

Sinusitis

also Conjunctivitis

Gram +

alpha hemolytic

OPTOCHIN SENSITIVE

extremely unstable in the environment

Normal flora of URT

spread by respiratory droplets

S. pneumoniae

virulence

polysaccharide capsule(antiphagocytic and antigenic)

enzymes (autolysin/pneunmolysin and IgA protease)

Pneumococcal Meningitis

-disease mechanism

-distinguishing features

-diagnosis

-prevention

Disease mechanism: lungs-->blood-->meninges

-in meninges, they replicate-->mac response (IL-1, TNF-alpha)

Distinguishing features

-prolonged fever (IL-1 is fever inducing)

-hearing loss; hydrocephalus

Diagnosis

-gram stain CSF

-isolate bacteria from CSF (confirmation)

-rapid tests for S. pneumoniae antigens

Prevention

Vaccine conjugate-Prevnar

Neisseria

basics

gram -

non-motile

oxidase +

cat +

aerobic

Neisseria meningitidis (vs. N. gonorrhoeae)

basics

ferments glucose AND maltose

polysaccharide capsule

Serovars

A=africa

B/C=developing countries and U.S.

W-135

Y

lives in respiratory tract

Which serovar of Neisseria meningitidis is on the rise and causes the most meningitis?

Polysac capsule (can survive in blood)

pili=adherence, antigenic variation, phase variation

LPS=Sialic acid addition (mimic RBCs)

IgA protease

outer memb proteins

winter

close contacts=military, schools, etc.

spread by droplet transmission (15% of healthy ppl carry it in their URT)

adhere to non-ciliated columnar ep (1-4 days)-->blood-->meningococcemia/LOS-->septicemia-->meningitis

it survives bc of its capsule!

Meningococcal meningitis

diagnosis

gram stain of CSF

culture of CSF, blood, or skin lesions

rapid agglutination tests-polysaccharide capsule (for partially treated patients)

Natural immunity-group specific opsonizing ab

quadrivalent meningococcal conjugate vaccine

-protects against A, C, W-135, Y (not B)

Haemphilus influenzae - tybe b

basics

pleomorphic gram -

facultative anaerobe

grows on Chocolate agar supplemented with NAD and Factor X

found in URT

Haemophilus influenzae - type b

virulence

polysac capsule

IgA protease

H. influenzae - type b

Who does it affect?

non-immunized kids btw 1 month and 3 yrs

INVASIVE! enters blood then invades meninges

H. influenziae - type b

diagnosis

gram stain CSF

culture confirmation (choc agar)

immunological tests to demonstrate abs to capsular antigen

Neonatal meningitis

causative bacteria

1. Strep agalactiae

2. E. coli

3. Listeria monocytogenes

Strep agalactiae

basics

gram +

beta hemolytic

cell wall antigen=B (GBS) 

CAMP test positive

bacitracin resistant

Strep agalactiae

virulence

polysac capsule with sialic acid

C5a peptidase

pre-term delivery

early rupture of membranes

prolonged labor

fever

Strep agalactiae

diagnosis

CAMP test positive

-express a phospholipase-->can synergize with the alpha toxin of S. aureus-->produces an ARROW HEAD hemolysis when put together on a plate

S. agalactiae 

disease course (child)

transmission occurs DURING BIRTH

early onset=less than 7 days after birth=pneumonia/bacteremia

late onset=more than 7 days after birth=meningitis

S. agalactiae 

disease course (mother)

prevention

post partum or post-surgical fever and endometritis-->bacteremia-->meningitis

mothers dont usually get this

screening is done 35-37 weeks gestation

gram -

facultative anaerobe

oxidase negative

ferments lactose-MacConkey agar (turns pink)

motile

K antigen=allows organism to adhere to meninges

others: O antigen (LPS), H antigen (flagellum)

Intestinal disease

UTI

neonatal meningitis

nosocomial infections

E. coli 

disease mechanism

transmitted DURING BIRTH-->K1 capsular antigen associated with the disease (may promote adherence to brain endothelial cells)

NO intrauterine transfer, unlike Strep agalactiae

Listeria

basics

short, non-spore forming

gram +

facultative anaerobe

ubiquitous in the environment

CONTAMINATES PREPARED MEATS, COLD CUTS, DIARY PRODUCTS (SOFT CHEESE)

Listeria

identifying features

intracellular parasite

grows at 4 degrees-food borne infections

small zone of beta hemolysis

TUMBLING MOTILITY only at 22-25 degrees

Listeria monocytogenes

roots of transmission

1. mother to child

2. food born infection

Listeria monocytogenes

lifecycle and pathogenesis

enters through GI tract-->macs + internalin (host protein) engulf Listeria-->Once inside it is encased in a phagosome-->fuses with lysosome-->should cause death of lysteria, but it doesnt bc of LYSTERIOLYSIN O. This allows it to escape into the cytoplasm of the host cell

ActA=causes formation of actin filaments. Gets a tail, which propels the organism to the cytoplasm of the host cell-->forces a protrusion into an adjacent cell-->produces a phospholipase

Listeriosis

risk factors

clinical presentation

Risk factors: impaired cell-mediated immunity (bc it is an intracellular pathogen)

Presentations:

1. Gastroenteritis=48 hrs following ingestion, diarrhea, fever, self limiting, no antibiotics

2. Bacteremia=fever, chills, myalgias

3. Meningitis=in ppl with risk factors

bacteremia

flu-like illness, no CNS involvement

early onset: infection IN UTERO, disseminated disease (sepsis), granulomas, meningitis, DEATH

late onset: acquired AT BIRTH, meningitis in 3rd-4th week, lower mortality

Listeriosis

diagnosis

How does our body fight it?

culture from blood, CSF

resistant to cephalosporins!

Immunity=cell mediated!

Clostridia

review

gram +

anaerobe bacilli-SPORE FORMER

DAMAGED BY OXYGEN (so difficult to send to lab for colonization bc it will be dead)

found in soil and human intestine

Clostridia

species

C. botulinum=botulism

C. tetani=tetanus

C. perfingens

C. difficile

C. tetani and C. botulinum

toxins and symptoms

they are not very aggressive, but elaborate very POTENT NEUROTOXINS

Botulinism=flaccid paralysis

Tetanus=Tetanospasmin... contractile paralysis, opisthotonos (arching of back), Lock Jaw

Eventually people will die bc of inability to BREATH

C. tetani

identifying features

large, blunt-ended rods

spores look like "TENNIS RAQUET"

anaerobe and motile

causes disease in old ppl--waning immunity

-metalloproteinase blocks the synaptic vesicle release of INHIBITORY NTs

-the toxin has a heavy and light chain-->light chain cleaves synaptobrevin-->prevents inhibitory release

C. tetani

disease mechanism

-the spore is inoculated into a wound (where there is little oxygen)-->7-21 day incubation period

-->multiply locally-->releases tetanospasmin

-->taken up by neurons-->retrograde (axonal) transport to CNS

Tetanus

diagnosis

and

prevention

muscle spasm, lock jaw, back spasm, paralysis of back muscles, trouble breathing

childhood immunization

IgG response to neutralize the toxin

Clostridium botulinum

properties

7 serotypes (A-G)

spores in soil and fresh water, fruits, veggies, honey, roasted peppers

germinate in anaerobic

BOTulinsm=BOTtles

Botulinum 

disease pathogenesis

The toxin is resistant to gastric enzymes

Metalloproteinase acts on presynaptic membranes at NMJs-->blocks the release of ACh

targets peripheral nerves

C. Botulinum

disease mechanism

Botulism

3 presentations

1. classic=12-36 hrs after ingestion, GI symptoms, blurry vision, dysphagia, PROGRESSIVE DESCENDING SYMMETRIC FLACCIDPARALYSIS

2. infant=2 weeks-8 months, ingest toxin or spore-->germinates in the gut, constipation, lethargy, paralysis, Floppy baby syndrome

3. wound=rare, inoculation of spores, IV drug users

Botulism

diagnosis

clinical observation

reportable disease

isolating/culturing of organism

Mycobacteria

basics

acid fast bacilli (pink, Ziehl-Neelson method)

mycolic acid=waxy in nature. They repel gram stain.

slow growth (4-12 weeks)

Aerobes

non-motile

non-spore former

Mycobacterium tuberculosis

Mycobacterium avium-intracellulare

MYCOBACTERIUM LEPRAE

causative agent of Leprosy 

low infectivity; requires prolonged contact!

has not been grown in culture, BUT has been grown on armadillios

Leprosy

distribution

transmission

rare in U.S. 

majore cause of disease worldwide (tropical and subtropical areas, Asia, Africa)

transmitted by nasal secretions, through nasal mucosa, or through skin lesion

LONG INCUBATION

chronic granulomatous disease, effects peripheral nerves, skin and nasal mucosa

Disease mechanism--Granulomatous disease

in Leprosy

mycobacterium is taken up by MACS and Schwann cells-->replicate-->release PGL-1, which prevents the fusion of a lysosome with a phagosome

-->survival of organism-->body responds by bringing in additional macs and immune cells

-->formation of granulomas

1. Tuberculoid=if individual has a strong immune response

2. Lepromatous=if poor cell-mediated response

Tuberculoid Leprosy

symptoms

diagnosis

granulomatous lesion has extensive epithelium giant cell and lymphocyte infiltration; FEW bacilli

symptoms: large, flattened plaques on the face, trunks and limbs (raised erythmatous edges and dry, pale, hairless centers). Patchy anesthesia

diagnosis=clinically and histologically. Lepromin skin test (type 4 hypersensitivity)