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BSCI424 Final
Dr. Briken, University of Maryland, College Park
118
Biology
Undergraduate 3
12/11/2013

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Term
family: Pasteurellaceae
Definition
genus: Haemophilus
Term
H. influenzae
1. first described by
2. subtyping
Definition
1. pfeiffer
2. serological rxn (capsule antigen) serotypes a-f (type b most important human pathogen 95% prevaccine)
biochemical reaction - biotypes 1-8
clinical/biological phenotypes - biogroup
Term
H. influenza biogroup aegypticus
Definition
causes Brazilian purpuric fever
Term
H. influenzae
general
Definition
gram -
pleimorphic, can assemble into filaments
fastidious (needs X, V factor)
facultative anaerobe
fermenter
catalase +
nonspore forming
nonmotile
Term
H. influenzae
pathogenicity
Definition
1. capsular antigen (Hib type b: PRP)
2. LPS (outer membrane)
3. fimbriae (adherance)
4. evasion of acquired IR: IgA protease (against Ab mediated opsonization and complement activation)
Term
1. opsonization
2. complement activation
Definition
1. bacteria in extraceullar space "nuetralized" by Ab and ingested by macrophages
2. bacteria in plasma, complemement activation -> lysis and ingestion
Term
evasion of IgA in mucosal surfaces

bacterial targets
Definition
IgA secreted as dimer, inhibits adhesion/toxins

targets: IgA protease at X, binding of IgA-binding proteins, then remove protective carbohydrates
Term
diseases
1. H. Influenza
2. Hi encapsuled, pre- type b- vaccine
2. H. ducreyi
Definition
1. ear (otitis) and sinusitis infection
2. pulmonary disease, epiglottis, meningitis
3. genital ulcer (std)/chancroid
Term
H. influenzae
diagnosis
Definition
blood, CSF (high#), bronchiolar lavage fluids

needs X/V factors so
satallite phenomenon on BAP w/ SA
chocolate agar culture (needs V factor)
Term
Haemophilus spp.
Definition
omnipresent
most nonencapsulated = NTHi (nontypeable)
few encapsulated/cause invasive disease
Term
H. influenzae
epidemiology

transmission
Definition
USA ~2.5k
type b
before 1987: 20,000 now: 12
rest <300

humans only known host
asymptomatic
colonizes nasopharynx
spread in air
temporal peaks Sept-Dec , March-May
Term
H. influenzae
preventation

Hi type A
Definition
1. active immunization w/ polysaccharide-protein conjugate vaccine
ex. mutant diptheria protein, tetanus toxoid, meningococcal group B outer membrane protein
2. capsular PRP from other pathogen

3 doses before 6 mo + boosters

no vaccine available for type A
Term
H. influenza treatment
meningitis:
less severe eg sinusitis/otitis:
prohphylaxis:
Definition
meningitis: cephalosporin
less severe eg sinusitis/otitis: ampicillin/cephalosporin
prohphylaxis: rifampin
Term
H. ducreyi (chancroid)
Definition
rare, 6 million cases worldwide
symptomatic mostly in men
10% coinfection w/ T. pallidum
treatment: cipro/erythromycin
prevention: condoms
Term
family: Alcaliganacea
Definition
genus: Bordetella
Term
Bordetella
characteristics
Definition
Gram - small coccobacillus
capsule
nonmotile
strict aerobe
urease, nitrate riduction -
oxidase +
after subclture:
pleimorphic, bipolar metachromatic staining, narrow zone of hemolysis
Term
Bordetella antigenic structure
Definition
heat stable antigen: LPS (Surface O)
heat labile: Caspular (K)
Term
Bordetella diagnosis
Definition
isolation: nasopharyngeal swab on BG Glycerin potato blood again

B. pertussis
3-4 days to grow
id by biochemical/agglutination tests
Term
Bordetella pathogenic factors
Definition
1. LPS
2. PERTUSSIS TOXIN(AB5 type) --> increase CAMP/secretion/mucus
3. PERTACTIC & filamentous hemagglutinins --> adhesins that bind to ciliated epithelium in lungs
Term
Bordetella clinical

stages
Definition
pertussis/whooping couch
by inhalation
1. incubation 1wk
2. catarrhal: inflamation of mucus membranes, 2wks (most bacteria)
3. paroxysmal: sudden attacks, 3wks
4. convalescent, 4+ wks
Term
bordetella epidemiology
Definition
host: human only
US: 20-30,000/yr
Term
bordetella
treatment
prevention
Definition
treatment: erythromycin, mucus suction
prevention: DTaP subunit vaccine (problem: antigenic variation)
chemoprophylaxis: erythromycin
Term
family: Chlamydiacea
genera: Chlamydia, Chlamydiphila
Definition
Chlamydia trachomatis
Chlamydiphila pneumoniae, psittaci
Term
Chlamydia characteristics
Definition
very small <.45 um
gram - rod
no peptidoglycan cell wall (penicillin resistance!)
strict intracellular growth!!
unique developmental cycle (ER-RB)
energy parasites
LPS/outer membrane proteins for serum ID
Term
C. psittaci

treatment
Definition
1. Zoonotic disease (birds)
Human infections Rare - mostly benign
2. In some cases severe disease may develop
-fever, chills, vomiting, diarrhea, (persist for more than 2 weeks without improvement)
-encephalitis, high fever, death if untreated
treatment: Tetracyclines and macrolides (not Penicillin)
Term
C. pneumoniae

treatment
Definition
1. Strict human pathogen
~200,000 cases of pneumonia annually (in adults)
2. Most cases are mild
3. Tetracyclines or macrolides (~2 weeks)
Term
C.trachomatis

Epidemiology
transmission
Definition
~ 500 million infections
- in underdeveloped countries 7-9million people blind/yr ( up to 90% are infected in some regions)
- In USA most common STD of bacterial origin (~1,000,000 reported cases per year)

transmission
sex, hand-eye STD-caused conjuntivitis
Term
silent epidemic
(clinical/treatment)
Definition
C. trachomatis

Urogenital Infections:
80% women asymptomatic
25% men asymptomatic (most males symptomatic!!)
discharge, cramps, painful urine/sex, fever, swollen testicles

untreated infections may lead to
in women: PID (Pelvic Inflammatory Disease): .250,000-500,000/yr USA
uterus/fallopian tubes/ovaries infection -> tissue scarring --> infertility

in men:
epididymitis (testicle inflammation) -> sterility 250,000/yr USA

conjunctivitis (pink eye):
eyelids swell, purulent discharge (neonatal 12mo), blindness (neonatal)

ocular trachoma:
- chronic/inflammatory/ulceration/eyelids turn inward, scarring/blindness (cornea opacity)
- long asymptomatic phase
- transmission: infectious eyedrops

ocular/genital infections: tetracycline
neonatal conjunctivitis/pnuemonia: macrolides
Term
C. trachomatis
Definition
no culture media available
use HeLa cell line for intracellular growth -> iodine staining for inclusion bodies (ELISA/immunoflouresence)
use DNA-probes/PCR, serology
Term
Chlamydia lifecycle
Definition
EB (elementary body)
metabolically inactive, extra-and intracellular, infectious (adhesins)

Reticulate Body (RB):
metabolically active, intracellular, non-infectious
Term
C. trachomatis pathogenicity
Definition
Zipper phagocytosis
TTSS
Tarp

inhibit phagosome-lysosome fusion (outer membrane protein/lipid?)

inhibit host cell death (apoptosis)
Term
family: Neisseriaceae
genera: Neisseria/Eikenella/Kingella
Definition
N. gonorrhoeae Very Common
N. meningitidis
Term
General Characteristics
N. gonorrhoeae and N. meningitidis
Definition
Gram - cocci
aerobic
nonspore forming
nonmotile
oxidase, catalase +
strict human pathogen
fastidious
35-37*C
capnophile (prefer higher Co2)
LOS (like LPS w/o O antigen ... polysaccharide vs oligosaccharide)

N. gonorrhoeae:
oxidizes glucose only, no capsule

N. meningitidis:
oxidizes glucose & maltose
diplococci
Term
Characteristics N. meningitidis (“Meningococcus”)
Definition
a) 10% world asymptomatic carrier
b) Acid produced from glucose AND maltose oxidation (not fermentation)
c) Polysaccharide capsule; 12 serogroups
d) Serogroups associated with disease: A,B,C,Y , W135 and unknown serogroup
e) Very sensitive to temperature above or below 37*C
f) in vivo diplococci, vitro: chain
Term
N. meningitidis

Epidemiology

Diagnosis
Definition
- Low prevalence, high mortality
- Colonizes posterior nasopharynx before manifestation of symptoms
- Asymptomatic carrier can be up to 20% in contact group and up to 80% during epidemic
- Household members are at 500-800fold increased risk to be infected!!
- Transmitted via aerosol
- 1,000-2,000/yr
- common cause of community acquired meningitis in adults

present in large #s in CSF, blood, sputum
culture (cat,ox +), sensitive to cold/dry
Gram - diplococci
PCR amplification
Term
N. meningitidis
Clinical manifestation
Treatment
Definition
Meningitis
- Abrupt onset
- no fever in neonates (<2months)
- Fever, severe headache, nausea , vomiting , altered mental status (disoriented), coma
- Petechiae (hemorrhagic spots) may occur
- Mortality up to 100% in untreated cases, Prompt treatment reduces it to 10%

Meningococcemia:
- Develops in 5-15% of menigococcal disease
- Abrupt onset
- High fever, chills, nausea, vomiting, headache
- Restlessness and delirium occur within hours
- Widespread purpuric skin lesions in trunk and lower extremities
- May coalesce to form large hemorrhagic lesions
Pulmonary insufficiency develop
- Many patient die within 24h after being admitted to hospital (40% fatality rate)

prophylaxis:
breastfeeding - passive immunization
subunit vaccine w/ polsaccharide capsular antigens for 2yo+ (antigenic variation :s )
chemoprophylaxis @risk

treatment:
susceptible to penicillin (vs. N. gonorrhea)
or cephalosporin
Term
N. gonnorrhoeae pathogenisis
Definition
infects mucosal surfaces of urogenital track and induces a local inflammation response

w/ OPA and LOS
OPA (protein 2): mediates firm attachment to cells
LOS:endotoxin activity
Term
pathogenesis
1. pilin
2. por protein 1
3. opa protein 2
4. transferrin, lactoferrin, hemoglobin- binding proteins
5. LOS
6. IgA1 protease
7. beta-lactamase
Definition
1. pilin - mediates initial attachment to nonciliated human cells; interferes w/ nuetrophil killing
2. por protein 1 - prevents phagolysosome fusion in nuetrophils (survival)
3. opa protein 2 - attachment
4. transferrin, lactoferrin, hemoglobin- binding proteins - iron & bacterial metabolism
5. LOS - endotoxin
6. IgA1 protease - found mainly in extracellular pathogens, destroys Ig
7. beta-lactamase - hydrolyzes beta lactam ring in penicillin
Term
Major biological functions/effects of LOS
Definition
- attachment to epithelial tissue
- stimulation of the production of bactericidal antibodies
- regulation of complement activation on the surface of organisms
- Induces inflammatory response (similar to LPS) mediation of toxic damage in the fallopian tube (sterility!)

- high frequency antigenic variation b/c different reading frames used -> evade antibody mediated immune response
Term
Concept: Phase variation
Definition
Alteration in the expression of surface antigens by bacteria (no mutation!)
How?
1)multiple genes for surface antigen
- differentially expressed (environmental signal?)
2) use different reading frames
Term
N. gonorrhoeae
Epidemiology
Definition
- Cause of 2nd most common STD of bacterial origin
~200,000 reported cases per year but probably closer to 700,000
- Most common in sexually active 15-24YO
- Risk factor: multiple sex partners
- Efficiency of transmission: 35% infected women to men; 50-60% infected man to women
- More than 50% of women remain asymptomatic but only less than 10% of men

- rates falling, incidence in certain groups remains high
- 40% C. trachomatics coinfection
- HIV cofactor
Term
Clinical Manifestations Gonorrhea
Definition
in Men
- Usually symptomatic
- restricted to urethra; purulent discharge (white and thick) and dysuria (painful urination) develop after 2-5 days in 95% of infected individuals
- Complications are rare but include: prostatitis, orchitis/Epididymitis (infection of testis)

women:
Women:
) main infection site is cervix; in 50% of cases symptoms develop; vaginal discharge/bleeding , dysuria and abdominal pain
) 50% of infections are ASYMPTOMATIC
) About 15% of infected women develop pelvic inflammatory disease; may lead to sterility

Bacteremia/Gonococcemia
- Disseminating infection with septicemia and infection of skin and joints occur in 1-3% of women (less frequent in men)
Increase incidences in women is due to asymptomatic (untreated) cases
- Fever, suppurative arthritis, pustular rash on extremities but not head and trunk

Opthalmia Neonatorum -> corneal scarring
- N. gonorrhoeae leading cause of purulent arthritis
Term
N. gonorrhoeae

Diagnosis
Treatment
Prevention
Definition
Diagnosis: Gram stain discharge/cervical swap (Gram - diplococci), PCR

Treatment: penicillin resistant
w/ uncomplicated infections: cephalosporin or flouroquinolones

for chlamydia coinfection: tetracyline(doxycycline) or macrolide (erythromycin)

Prevention: condoms, vaccine
antibiotic eye drops w/ newborns (contains erythryomycin, iodine, silver nitrate)
Term
family: Spirochaetaceae
genera: Treponema/Leptospira/Borrelia
Definition
Treponema pallidum
Term
Treponema pallidum characteristics
Definition
- Gram - Spirochetes
- No capsule
- Thin, helical (o.1x 5 to 20um)
Too thin to be observed by light microscopy (including gram/giemsa staining!)
- Three periplasmic flagella (motile!), hidden from host immune response
- Cannot be grown in vitro except on selected cultured cell lines (like Chlamydia)
- Human only known host
Term
T. pallidum
epidemiology
Definition
3rd most common STD of bacterial origin in USA, 30-40,000 cases/yr US
Human only known host
Spread by sexual contact via breaches in the epithelium
Transmission occurs primarily during early stages of disease
Mother to fetus transmission is possible (bacteria can cross placenta)

~30-40,000 total cases of Syphilis per year in US
-age group 20-40 most affected
-increase in cases between 2000-2006
-300-400 case of congenital syphilis per year
-Syphilis increases chances of acquiring HIV by 2-5fold
Term
T pallidum (syphilis)
clinical
Definition
- men & women symptomatic
- primary chancre on genitals
- painless lesion w/ high #s bacteria -> trasmission
- heals spontaneously w/i 2mo but bactera spread into blood & lymph system

secondary syphilis:
- disseminated disease
- flu like syndrome
- infectious skin rash
- symptoms resolve spontaneously
-> enter latent phase of disease

tertiary/latent syphilis:
- 10-15% , 10-20yrs after infection
- chronic inflammation -> organ/tissue destruction (loss of coordinated muscle movement, blindness, dementia)
- mother infectious for ~4yrs

congenital:
- infection in utero
- multi-organ malformation, fetus death
- newborns w/o symptoms may suffer from teeth/bone malformations, blindness, deafness
Term
T pallidum
diagnosis
Definition
- serological tests/staining/ELISA

problem: treponemas (NOT T. pallidum) are part of normal microflora in oropharynx -> crossreactivity of antibodies
Term
T pallidum
prevention
treatment
Definition
condoms but sores can be outside of area, no vaccine

penicillin, tetracycline
Term
Family: Spirochaetaceae
Genera: Borrelia
Definition
in US & Europe: B. burgdorferi
in Europe & Asia: B. garinii, afzelii

B. recurrentis
Term
Borrelia characteristics
Definition
- spirochetes, thin, helical (.5x8to30um)
- 7-20 periplasmic flagella
- can be observed w/ Giemsa stain
- can be grown in vitro but very complex media requirements (generation times >18hrs) ..diagnosis not by culture
- vector-borne disease
Term
Borrelia infections
Definition
B. recurrentes: relapsing fever epidemic (louse-borne, reservoir: humans) <- crowded & unsanitary conditions, only in few underdeveloped countries

many Borrelia species: relapsing fever endemic (reservoir: rodents, soft-shelled ticks), found in western USA

B. burgdorf in US: lyme disease (reservoir: rodents, deer, hard-shelled ticks)
Term
Borrrelia
Relapsing fever
Definition
epidemic: B. recurrentes

- 1wk after bite, abrupt onset of shaking chills, fever, muscle ache, headache (=bacteremic phase = FEBRILE PERIOD) ..resolve after 3-7days (clearance of bacteria)

and return in 1 wk (AFREBRILE PERIOD)

subsequent febrile periods are less severe

evasion of immune response via antigenic (phase) variation ...VMPs: variable major proteins

diagnosis: febrile pd = high #s = detection in blood sample via Giemsa staining

treatment: tetracycline & erythromycin, no vaccine
Term
Lyme disease
Definition
B. burgdorf

early infection (stage 1)
- 60-80% erythma migrans (rash), expands over time, up to 50cm

dissmenation (stage 2)
- spread of bacteria into bloodstream
- fatigue, chills, fever, headache, muscle & joint pains
- swollen lymph nodes (lymphadenopathy)

persistence (stage 3)
- variable, may appear wks-yrs after bite
- meningitis (headache, stiff neck, fever)
- bell's palsy (paralysis of facial muscles) <- tumor, lyme disease, virus
- arthritis (swelling, discoloration)
- disturbance in memory/mood/sleep
- numbness in hands or feet

95% cases in 12 states, seasonal incidence w/ feeding pattern of ticks (higher in late spring/early summer)

diagnosis:
- difficult, variable, resemble viral infections ..based on patient history/exposure
- microscopy not useful
- serology w/ stage 1-2 (potential of cross-reactivity)
- PCR amplification

treatment: doxycline (2-3 wks, twice daily), may recur but usually resolved w/ 2nd treatment

prevention:
- DEET insect repellent, use permethrin on cloth: kills ticks on contact
- removal w/i 36hrs prevents infection
- vaccine available (withdrawn due to poor sales)
Term
family: Aeromonodaceae
genus: Aeromonas
Definition
A. hydrophila
Term
A. hydrophila characteristics
Definition
Gram - rod
- Facultative anaerobe
- Resembles members of Enterobacteriaceae
- Motile with monotrichious flagellum
- Can grow in temp as low as 4C
Term
A. hydrophila epidemiology
Definition
- ubiquitous in fresh/brackish (intermediate salt) water
- fish/amphibian pathogen
- in humans: mostly w/ immunocompromised
foodborne -> gastroenteritis
swimming -> wound infections, necrotizing fascitis
systemic disease
Term
Aeromonas pathology/treatment
Definition
- Acute Gastroenteritis in children, Is self-limiting; only supportive treatment

- Chronic Gastroenteritis* mostly in adults (lasts for weeks )
- Systemic Infections* and/or wound infections
***antimicrobial treatment: flouroquinolone (ciproflaxin)
resistant: penicillin, cephalosporin, erythromycin
Term
family: Vibrionaceae
genus: Vibrio
Definition
V. cholerae
V. parahaemolyticus
V. Vulnificus
Term
Vibrio characteristics
Definition
Gram - curved rods
Broad temp. range (140-400C)
Tolerate high pH (basic) but susceptible to acid environment (stomach!)
Single, polar flagellum (monotrichous)
LPS (O-antigen) for serum ID
Term
V. parahaemolyticus, V. vulnificus
clinical
Definition
foodborne: gastroenteritis (self-limited)
wound infections: tissue necrosis, septicemia

infections rare in US, but most common form of bacterial gastroenteritis in Japan/Southeast Asia (V. parahaemolyticus)
Term
V. cholerae
epidemic serotypes
epidemiology
transmission
Definition
human pathogen (found by Koch)
water quality: cholera outbreaks (by Snow)

serotypes O1 (El Tor), O139 associated w/ epidemics..produce cholera toxin
O1 doesn't produce capsule (no disseminating disease)

7 major pandemics since 1816
3-5 million cases, 100,000-120,000 deaths
in US: due to travelers/contaminated seafood

multiply in water, bacteria shed in high amounts in feces of patients/asymptomatic (75%), recovering (for 1-2wks)

no person-to-person infections
requires high infectious dose (10E6-10E8 bacteria)

"seasonal epidemics of cholera inversely correlate w/ the prevalence of environmental cholera phages"

new cholera outbreaks when introduced to environment w/o phages
Term
V. cholerae
clinical
treatment
Definition
cholera (only O1, O139):
abrupt onset 2-3days
water diarrhea
"rice-water" stool (colorless/odorless/speckled w/ mucus:bacteria!)
vomiting (only 20%)
up to 1L fluid lost/hr (adherence is key for virulence!)
--> severe dehydration, cardiac/renal failure
60% mortality if untreated, 1% if treated

treatment: rehydration, antibiotics shorten/reduce severity: Deoxycycline for adults & TMS for children
prevention: oral vaccine available

gastroenteritis (by serotypes that don't express cholera toxin)
Term
V. cholera
pathogenesis
factors favoring/impeding eradication
Definition
ETEC, LT-1, cholera toxin: severe loss of electrolytes/water
toxin co-regulated pilus: adherence
colonization factor: adherence
other toxins that increase intestinal fluid secretion (diarrhea by non-toxigenic V. cholera)

toxins are grouped in pathogenic island on chromosome and co-regulated (ToxR regulator) - common feature of virulence factors among all pathogenic bacteria

eradication: fragility of organism, high infectious dose, no person-to-person transmission, short incubation period

impeding eradication: persistence in aquatic environment, increase in population density, inadequete vaccine, limited protection from natural immune system, public health failure, flexibility/variety of toxigenic strains
Term
V. cholerae lab diagnosis
Definition
- survive poorly in dry/acidic environment, innoculate promptly
- MacConkey: nonlactose fermenting
- TCBS enrichment media
- PCR based detection of toxin gene presence
- serology: O-antigen
Term
Legionnaire's disease
risk factors
Definition
older, lung disease (smokers), immunodefficient, diabetic, renal disease, cancer, nosocomial disease

male 3X females

X foodborne/person-to-person transmission
Term
family: Legionellaceae
fenus: Legionella
Definition
L. pneumophila
Term
Legionella characteristics
Definition
Mildly Gram - bacillus (hard to stain, best: Silver stain)
Motile (monotrichious, temp sensitive expression @37*C)
Aerobe
Non-fermentative, derive energy from metabolism of amino acids
48 species, 50% associated w/human disease

growth conditions:
>37*C
media: high levels of Cysteine, inorganic iron, low sodium, charcoal (to absorb free radicals)
3-5 days to grow

found in non-marine aquatic environments
can survive in tap water @RT for 1yr+
lives as biofilm (on lakes/ponds, in pipes, heat exchange surfaces, water cooling towers) w/ certain algae(provide nutrients)/protozoa/fungi

mode of transmission: aerosolized water source

avg relative humidity 65%
Term
Legionella life cycle
Definition
common host: amoebae (nature's macrophage)
accidental host: human

coiling phagocytosis -> phagosome does not acidify/fuse w/ lysosome -> phagosome surrounded by ER studded w/ ribosomes -> multiply in phagosome -> rupture -> host cell lyses, bacteria escape
Term
Legionella clinical
Definition
- asymptomatic common
- symptomatic:
1. Legionnaires disease (more severe)
2. non-pnuemonic form: pontiac fever
Term
Legionella pathogenesis/treatment
Definition
*Legionnaires disease
2-10 day incubation
fever/anorexia/headache, sometimes diarrhea/confusion
recruit nuetrophils/monocytes/bacterial enzymes (protease) -> destructive alveolar inflammation
severe pneumonia -> respiratory failure if untreated
mortality 20-50%
TREATMENT:
macrolides: erythromycin/azithromycin(penetrate macrophages)
flouroquinolones (ciproflaxin)
RESISTANT to beta-lactams

*pontiac fever
2day incubation
flu-like symptoms that self-resolve in 2-5 days
treatment symptomatic, no antimicrobial therapy

*Prevention
expensive: treat water supply w/ UV
in development: biocides, vaccines
Term
Legionella lab diagnosis
Definition
DCYE agar: slow growth >5days

DFA (direct flourescent antibody) test
sensitivity: 25-75% :/
specificity >95% (antibodies serotype specific)
need high concentration of bacteria to detect - difficult b/c intracellular

Urine antigen test
only detects L.pneumophila serogroup 1
sensitivity: 70-100%
100% specific

NAA (nucleic acid amplification) assays: PCR
unknown sensitivity/specificity

serology
paid sera need 2 samples 14d apart
Term
Legionella epidemiology
Definition
8,000-18,000 hospitalized w/ Legionnaires disease

many undiagnosed

most late summer/early fall
Term
family: Helicobacteraceae
genus: Helicobacter
Definition
H. pylori
>20 species
Term
Helicobacter discovery
Definition
silver stain: black bacilli line the pilus, easly seen

Warren: bacteria:ulcers w/ EM
Marshall: was Hp a pathogen? antibodies? antibacterial heal? disease process?
Warren drank 10E9cfu, vague illness/halitosis, vomiting/no acid present -> histological gastritis: Hp is pathogen


heavy metals as antibacterial-
Arsenic, Mercury: syphilis
Bismuth: gastric disease

H. pylori susceptible to bismuth
bismuth + antibiotic = 75% cure rate in ulcer patient
Term
H. pylori epidemiology
Definition
half the world infected, 10-15% ulcer disease, stomach cancer

9 out of 10 ulcers caused by H. pylori

25 million (10%) Americans have ulcers

contagious (oral, feces), person-to-person transmission
Term
H. pylori disease manifestation
Definition
duodenal ulcer
more widespread inflammation: gastric ulcer, gastric/pancreatic cancer
Term
H. pylori characteristics
Definition
Gram - spiral/helix, can change to coccoid in culture
motile, multiple polar flagella (lophotrichous)

37*C optimal

microaerophilic atmosphere (5-7% O2, 5-10% CO2)

urea absent from gastric juice of Hp patients
splits urea -> ammonia + HCO3- -> co2 + water
co2 detected by breath test + diffuses into blood stream

protects itself from acid -> neutralization of stomach pH
Term
H. pylori pathogenicity
Definition
most extracellular, colonize stomach epithelium
some penetrate epithelial cells and have to deal w/ phagocytes(macrophages) of the host immune system

LPS, Flagella
CagA pathogenicity island: encodes T4SS, CagA protein (disrupts intracellular junctions)
Type 4 SS (injects effectors into host cell)
Adhesins (VacA, SabA, BabA)

VacA exotoxin
*adhesin, induces epithelial cell death, inhibits phagosome maturation, inhibits T-cell activation
*forms CI-channel in host cell phagosomes and disturbs osmolarity -> influx of water and formation of megasomes
Term
H. pylori diagnosis
Definition
breath tests
*drink labeled substrate of urea: see if split by urease (enzyme that H.pylori uses to metabolize urea)
*detect increase co2 in breath

endoscopy: sample of stomach lining is taken, urease tested

serology: detects antibodies against bacteria (problem: current or past infection?)

ELISA: detects H. pylori antigens in stool (only positive if current infection)
Term
H. pylori
treatment/prevention
Definition
anti-acid and bismuth for 2wks: 90% cure rate

no vaccine
Term
famiy: Campylobacteraceae
genera: campylobacter
Definition
C. Jejuin
C. Coli
C. upsaliensis
Term
campylobacter characteristics
Definition
Gram - comma-shaped (sometimes spiral)
small .2-.5um
microaerophilic growth requirements
motile
capsule
catalase, oxidase, hippurate +

for serum ID:
LPS/LOS (O-antigen)
Flagella (H)
Capsule (K)
Term
C. jejuni culture
Definition
42*C (poultry)
filter .45um samples before culture
include antibiotics into medium: TMS, vancomycin
Term
Campylobacter epidemiology/transmission
Definition
2 million/yr
(not including C. upsaliensis, not easily detected)
most cases: sporadic events (not outbreaks), not reported to CDC

95% caused by C. jejuni (80% of supermarket chicken infected)
2-5% by C. Coli

NO person-to-person spread

bacteria do not multiply in food

low infectious dose
Term
Campylobacter clinical
Definition
*gastroenteritis
acute enteritis (2-5days after exposure): diarrhea (can be bloody) malaise, fever, abdominal pain - lasts 1wk

*bacteremia
1.5cases per 1000 infections

*guillan-barre syndrome
complication of infection
autoimmune-like disease of peripheral nervous system
pain, weakness, paralysis of extremities
recovery requires weeks to months
Term
Campylobacter pathogenesis research
Definition
little understood
chicken/mouse don't reflect human pathology
knockout ferrets used

genome sequenceing, signature-tagged mutagenesis, genetic tools for introducing & deleting genes
Term
Campylobacter pathogenesis
Definition
Type 4SS (encoded by virulence plasmid) - contain conjugative pilus (DNA transfer)
flagellum (important for motility, adhesion, and protein secretion!!)
LOS: adhesion, serum resistance, autoimmune disease
CDT (cytolethal distenting toxin): inhibits cell progression -> cell death
capsule
Term
Campylobacter diagnosis
Definition
microscopy is insensitive
culture on specialized media (including antibiotics) under microaerobic conditions @ 42*C

catalase, oxidase, hippurate +
Term
campylobacter treatment/prevention
Definition
treatment:
gastroenteritis: self-limiting
erythromycin

prevention: chlorinated water, pastuerization
Term
Case Studies: STDs & Severe Infections
Definition
immunize: HepA,B, HPV (complication: cervical cancer)

rule of 3 exception: candida albicans (fungi), phthirus pubic lice-crabs (ectoparasite)

CDC (for reporting)
Compliance w/ treatment
Counseling on risk reduction
Condoms

diaphragms/spermicides - not recommended
birth control pills/implants - do not protect against STDs though they should protect against another sexually transmitted "condition"

*lethal infections
-bacteremia: very transient bacteremia may occur w/ common mucosal trauma (teeth brushing), may or may not result in illness
-septicemia: bacteremia w/ sequelae, acute symptoms related to organism specific characterestics (eg toxins) & body response to invasion, extremely serious (rapid onset, lethal)

more STDs
lower PIDs
more sepsis hospitalizations

*severe overwhelming infection
-septecemia/meningitis: N. meningitidis, H. influenza B
s.pnueomnia, S.typhi,S.aereus, Gp A,B strep
opportunistic in immunocompromised hosts: MRSA, Klebsiella, Pseudomonas, Coliforms
-wound: C. perfringens, C. tetani
-biowarfare: C. botulinum

*Meningococcal Meningitis & Sepsis
purpura/hemorrhagic rash, lassitude, fever, disorientation, Brudzinski's sign & stiff neck, seizures, need controlled ventilation, clotting factors, platelets -> cardiac arrest, death
preventative measures: meningococcal 4valent vaccine (A,C,Y,W135)

*C. perfringens
gas gangrene
inability to move, fever, elevated WBC count

*infantile botulism (C. botulinum)
100 cases/yr, 6wks-6mo
soil/honey/corn syrup
neurotoxin A,B,E,F
eye ptosis, poor head control, constipation, fever, anorexia,
rx: botulism immune globulin urgently!!
curable w/ early intervention, may be lethal - supportive intensive care, antibiotics worthless
Term
family: Francisellaceae
genus: Francisella
Definition
species: F. tularensis
subspecies:
F. tularensis subsp. holarctica, novicida, mediasiatica

tularemia: highly infectious zoonotic disease (low ID), found in rodents/hares/rabbits/biting flies/ticks/even amoeba - fever

acquired by arthropod bite, infected meat/water, contaminated aerosols
Term
F. tularensis characteristics, epidemiology
Definition
Gram - coccobacillus
small .2um-.2*.7um
nonmotile
obligate aerobe
catalase -
prefers low T
fastidious growth, requires cysteine (BCYE agar)
non-pigmented
non-hemolytic
LOW infectious dose - BSL3
obligate intracellular (primarily in macrophages)

rare disease by natural route of infection
100-200/yr
mortality 1-30%
farmers & lanscapers in endemic areas
Term
F. tularensis
strains
antigenic structure
Definition
Jellison Type A (subsp tularensis):
tick-borne isolate of rabbits, in USA
highly virulent, focus of bioweapons
80% of human cases

Type B (subsp holarctica:
less virulent, some highly virulent
associated w/ water-dwelling rodents
LVS (live vaccine strain) is this subspecies

capsule, polysaccharide
cell wall & envelope: endotoxin activity (LPS) reduced -> anti-LPS antibodies can be used for serology
Term
F. tularensis clinical
Definition
tularemia:

ULCERoglandular -> pain & swelling
OCULoglandular <5%

typhoidal (systemic)
-headache,chills,high fever, confusion
-NO rash or adenopathy

oropharyngeal & gastrointestinal (ingestion of contaminated meat)
-sore throat/mouth, diarrhea, vomiting

pneumonic
- high morbidity & mortality
Term
F. tularensis immunity
Definition
IgM & IgG persist but offer little immunity

cellular immunity linked to activated macrophages important to resistance (b/c intracellular pathogen)
Term
F. tularensis diagnosis
Definition
culture:
dangerous due to possibility of lab acquired disease
fastidious & slow growing

serologic
- flourescent antibody to ID organism in tissue or serum
- agglutination test most common (4-fold increase in titer)
Term
F. tularensis treatment/prevention
Definition
treatment: tetracycline or fluoroquinolones or aminoglycosides

immunization: attenuated live vaccine (LVS) for high risk individuals, type B strain, not approved by FDA yet
Term
bioterrism agents
Definition
Category A 'select' agents: Francisella tularensis
- highest risk to national security
- easily disseminated or person-to-person
- high mortality
- requires special action for preparedness

Category B: Brucella
-moderately easy to disseminate
-moderate morbidity, low mortality
-require surveillance

category C
-emerging pathogens
-could be weaponized

F.tularensis WHO model
50kg dried type A strain
population: 5 million
cases: 250,000
1/3 would flee
1 million require antibiotics
with antibiotics
10% (25,000) would require hospitalization
1% (2,500) would die due to tularemia
Term
family: Brucellaceae
genus: Brucella
Definition
B. abortus, melitensis, suis, canis

cow <-abortus
melitensis -> goat
pig <- suis
Term
Brucella
Definition
Gram - coccobaccillus
non-motile, non-hemolytic, non-encapsulated, non-fermentative
require complex media to isolate
strict aerobe
oxidase + catalase +
Term
Brucella pathogenicity, epidemiology
Definition
intracellular growth key to virulence
- enter through lipid rafts on host cell, inhibit fusion to lysozyme, multiply in specialized organelles associated w/ ER

T4SS
smooth cell wall may contribute to survival w/i macrophages (rough strains bind antibody and are less likely to survive)
O-antigen of LPS
group specific proteins
cell wall carbohydrates bind to B-cells

animals recover but excrete bacteria
90% of human cases via contact w/ infected material (occupational hazard)

NO person-to-person transmission
Term
Brucella clinical
Definition
- enter bloodstream/lymphatics/nodes
-intracellular localization w/i macrophages
-infected tissue become granulomatous (abscess formation)
-weakness, fatigue, chills,sweat,joing&muscle pains, nervousness & mental depression
-can become chronic, last for years
-complications: endocarditis, lesions in organs, joint or bone infection, ___________
Term
Brucella immunity
Definition
-IgM, IgG antibodies produced
-macrophages & monocytes are key to microbe destruction & elimination of infection -> dissemination in body :/
Term
Brucella lab diagnosis
Definition
samples from blood, spinal fluid, bone marrow, tissue
isolation of Brucella definitive

culture conditions:
- solid medium: serum-dextrose or serum-potato-infusion or blood agar
- incubate @ 10% CO2
- hold for 21-35 days before 'negative'
-antibiotics included to inhibit overgrowth

serological (sensitive & reproducible): tube or card agglutination test, ELISA
Term
Brucella Treatment/Prevention
Definition
treatment: 6wk antibiotic combinations

prevention: control animal disease, animal vaccine usage, pastuerize
Term
family: bacillaceae
genera: bacilla/clostridium
Definition
species:
B. anthracis, B. cereus
common: C. difficile, C. perfringens
uncommon: C. septicum, botulinum, tetani, tertium
Term
Bacillus
characteristics

B. anthracis
Definition
first anthrax vaccine: pasteur's heat attenuated

Gram + rods
30-45C
spore forming
capsule
facultative anaerobe
mucoid colony

B. anthracis
large rods
can be chains, nonmotiel
spore in 2-3 day culture, not clinical specimen
Term
spores
Definition
Gram +
bacillus, clostridium
no detactable metabolism - cryptobiotic

1. dna
2. replication
3. chromosome seperation
4. protoplast
5. forespore
6. maturation
7.release
Term
B. anthracis pathogenicity
Definition
edema toxin: increase CAMP/edemas (fluid accumulation in tissue)

capsule: anti-phagocytic/complement/antibiotic - ONLY EXPRESSED IN VIVO

lethal toxin: zing metalloprotease INHIBITS release of proinflammatory cytokines from macrophages & induces cell death

disease of herbivores (spores on grass)
95% cases from innoculation of spores on human skin (from contaminated animals - inhale/incubate/ingest)
no person-to-person spread

inhalation: woolsorter's disease
Term
B. anthracis clinical, diagnosis, treatment
Definition
cutaneous anthrax:
-painless papule -> ulcer -> necrotic eschar (black wound)

grastrointestinal anthrax:
ulcers @invasion site -> regional lymphadenopathy, edema
intestinal infections: nausea, vominting, bloody diarrhea, sepsis (50% mortality)

inhalation anthrax
- latent pd (2mos)
- 1st phase: enter lymphatic/blood circulation, nonspecific and mild (fever, headache, cough)
- 2nd: fever, lung edema, enlargement of mediastinal lymph nodes, 50% meningeal symptoms
mortality close to 100% w/i 3 days of second phase due to bacterimia/toxic shock/respiratory failure


diagnosis: overwhelming amts of bacteria: microscopy, PCR

treatment: penicillin, CIPROFLAXIN
resistnant to sulfanomides (TMS) & cephalosporin

vaccinate animals - but spores persistent
Term
B. cereus
Definition
motile (peritrichous), beta hemolytic, ubiquitous

heatstable enterotoxin: emetic disease (vomiting and diarrhea)

heatlabile enterotoxin: diarrhea only
~ V. cholera toxin, increase CAMP/watery diarrhea

^self-limiting

ocular infections: ww/ soil contaminated object, blind in 48hrs
nosocomial/IV: endocarditis, bacteremia, pnuemonia, meningitis only in severely immunosuppressed patients

^treatment:
-mycin (glycopeptide-vancomycin, lincosamid-clindamycin),
ciproflaxin
Term
Clostridium

C. perfringens
Definition
Gram + spores
motile peritrichous flagella (except C. preferingens)
ubiqoutous (soil, water, sewage)
saprophytes
produce volatite fatty acids
ferment wide variety of organic compounds and produce large amounts of gas (co2, h2)

C. perfringens
rectangular rods
nonmotile
hemolytic
rapid growth (8-10 min doubling time)
Term
C. perfringens pathogenicity
Definition
in 5 groups A-E

by all 5 types:
Alpha toxin (phospholipase C) : HEMOLYSIS, NECROTIZING

by A:
enterotoxin: alters membrane permiability in ileum, is super antigen, heat labile -> watery diarrhea

A: found in intestinal microflora, foodborne illness (from soil/water)
Term
C. perfringens
Definition
*soft tissue infections
1. cellultis - localized edema w/ gas formation (nonpainful, treatable)

2. suppurative myositis - pus accumulation in muscles, treat aggresively

3. myonecrosis/gas gangrene (after 1wk):
- pain, muscle necrosis, shock, renal failure, death
- gas due to metabolic activity of bacteria - abundant growth
- no inflammatory cells - lysed by bacterial toxins
- mortality: 40-100%

^treatments: penicillin

*gastroenteritis
- self-limiting
- short incubation pd (8-24hrs)
- caused by enterotoxin
- no fever or vomiting (generally)

diagnosis:
nagler's rxn: precipitates alpha toxin
Term
C. difficile
Definition
- sensitive to oxygen
- antibiotic associated diarrhea, colitis

toxin A, B: modify GTPase to be inactive <- enzyme linked immunoassay for diagnosis

5% asymptatic carrier (in hospitals: 20%)

mortality: 25% in elderly

350,000 cases (30,000 deaths)

treatments: metronidazole (good anaerobic!!), vancomycin, fecal transplant
Term
C. tetani
Definition
tetanus toxin/tetanospasmin
large A-B toxin

inhibits nuerotransmittor glycin,gaba -> spastic paralysis, lockjaw (heart muscle not affected)

14% neonatal death in underdeveloped countries
1 million cases
500,000 deaths

*vaccine, booster shots every 10yrs
Term
C. botulinum
Definition
large, fastidious
botulinum toxin (A: endopeptidase activity, cleaves acetylcholine protein; B: binds to receptor on nuerons)

flaccid paralysis

foodborne 30/yr
infant 100/yr (mortality 1-3%)

treatment: penicillin/metronidazole
antitoxin: only effective for unbound toxins
decreases mortality from 60% to 4$
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