Emily's Microbiology Post-Spring Midterm

Front 1

How long does hepatitis have to be present to be considered "chronic"?

Back 1

>6 months

Front 2

Which types of hepatitis viruses can cause chronic viral hepatitis?

Back 2

B, C and D

Front 3

How is Hep. A transmitted?

Back 3

Hep. A is known as "infectious" hepatitis, and is transmitted person to person by fecal/oral route

Front 4

How is Hep. B transmitted?

Back 4

Hep. B is known as "serum" hepatitis, and is transmitted parenterally by blood or blood products.

Front 5

What are the non-A non-B hepatitis viruses?

Back 5

Hep. E (enterically transmitted)
Hep. C (parenterally transmitted)
Hep. Delta virus

Front 6

Can the different types of hepatitis be distinguished histologically?

Back 6

No, viral hepatitis looks like the hepatitis caused by other conditions.

Front 7

What conditions can result from chronic viral hepatitis?

Back 7

Cirrhosis
hepatocellular carcinoma

Front 8

How are the causes of hepatitis differentiated and diagnosed?

Back 8

Serological testing

Front 9

What family/genus does Hep. A belong to?

Back 9

Picornavirus family
Hepatovirus genus
formerly classified as enterovirus 72

Front 10

Hep. A virus
+/- ss/ds DNA/RNA
icosahedral/helical
enveloped/naked

Back 10

+ ss RNA
icosahedral
naked

Front 11

What is Hep. A's capsid composed of?

Back 11

VP1, VP2, VP3 and VP4

Front 12

How many serotypes of Hep. A virus exist?

Back 12

1
(made it easier to make an effective vaccine!)

Front 13

What is different about Hep. A virus' CPE compared to the CPE of other Picornaviruses?

Back 13

Very little CPE b/c it does not shut off host cell protein synthesis

Front 14

How is Hep. A transmitted?

Back 14

fecal/oral, therefore:
- close personal contact (household, sexual, daycare)
- contaminated food, water
- ONLY RARELY parenterally

Front 15

How does Hep. A's physical stability compare to other picornaviruses?

Back 15

more stable
resistant to chlorine
resistant to 90 degree temp. for 10 minutes

Front 16

Who is at risk for Hep. A infection?

Back 16

Everyone, esp. homosexuals, travelers, military, daycare children/workers/parents, IVDA

Front 17

How prevalent is Hep. A among US adults?

Back 17

40% seropositive

In developing countries, the majority are infected in childhood.

Front 18

Who is more severly affected by Hep. A: children or adults?

Back 18

Adults (children do not generally become jaundiced)

Front 19

How long is Hep. A's incubation period?

Back 19

30 days (short)
range: 15-50 days

Front 20

Prevalence of jaundice in Hep. A by age group:

Back 20

<6yo: <10% jaundiced
6-14yo: 40-50%
>14 yo: 70--80%

Front 21

What is the prognosis for Hep. A patients?

Back 21

Good: virtually all recover in 6-8 weeks and have lifelong immunity

Front 22

How can you prevent Hep. A transmission?

Back 22

Avoid exposure
Passive immunity (pooled gamma globulin decreases occurrence of dz by 7-8 fold)
Vaccine (highly effective capsid protein subunit, produced by recombinant DNA technology and provides life-long immunity)

Front 23

What family does Hep. B virus belong to?

Back 23

Family Hepadnaviridae

Front 24

Hep. B virus:
+/- ss/ds RNA/DNA
icosahedral/helical
enveloped/naked

Back 24

circular, partially-dsDNA
icosahedral capsid
enveloped (but not in the true sense?)

Front 25

Hep. B's capsule is composed of:

Back 25

HBsAg (Hep. B surface antigen)
-present in bloodstream during acute dz and in carriers
-produced in excess, also makes empty 22nm filaments and spheres
-used to make vaccine

Front 26

When would Anti-HBs be present in a patient's blood stream?

Back 26

Anti-HBs = Abs to HBsAg (Hep. B surface Ag)
present in convalescent phase of acute Hep. B
AND after successful vaccination
NOT present in chronic Hep. B (though HBsAg is present)
HBIg derived from serum with high anti-HBs titer is effective in preventing Hep. B infection and dz

Front 27

When would Anti-HBc be present in a patient's blood stream?

Back 27

Anti-HBc = Abs to HBcAg (Hep. B core Ag)
present in all patients with any form of Hep. B infection (including during the "window period")
NOT induced by vaccine

Front 28

What is the "window period"?

Back 28

Time in an acute Hep. B infection when HBsAg is no longer detectable and anti-HBs is not yet detectable.

IgM-anti-HBc is present during this time

Front 29

When would IgM-anti-HBc be present in a patient's blood stream?

Back 29

IgM-anti-HBc = IgM Ab to Hep. B core Ag,
present in high titers in patients with acute Hep. B
may be only marker during window period

Front 30

When would HBeAg be present in a patient's blood steram?

Back 30

HBeAg = soluble protein derived from Hep. B core
present when circulating Hep. B virus is in the blood.
seropositive for this Ag is highly infectious

Front 31

When would anti-HBe be present in a patient's blood stream?

Back 31

anti-HBe = Ab to HBeAg (soluble protein derived from core)
present 16 weeks after exposure in acute Hep. B
presence in chronic carriers decreases infectious capability

Front 32

How is Hep. B transmitted?

Back 32

percutaneous or sexual exposure
mother to newborn

Front 33

How prevalent is Hep. B among US adults?

Back 33

3-5% seropositive

Front 34

What is the Hep. B prodrome and what causes it?

Back 34

Rash, arthritis, glomerulonephritis
immune complexes in early phase of acute infection

Front 35

What is the incubation period of Hep. B?

Back 35

60-90 days
range: 45-180 days

Front 36

What % of Hep. B patients are jaundiced, by age group?

Back 36

<5yo: <10%
>5yo: 30-50%

Front 37

What % of acute Hep. B patients die?

Back 37

0.5%-1%

Front 38

Chronic Hep. B infection develops in...

Back 38

>90% of infected neonates
80% of infected perinatal patients
50% of infected infants
5-10% of infected adults

Front 39

What complications can result from chronic Hep. B infection?

Back 39

15% of carriers develop primary hepatic carcinoma (younger at infection = higher risk)
1-5% develop cirrhosis
15-25% die prematurely from chronic liver dz

Front 40

Tx acute Hepatitis of any kind

Back 40

supportive care

Front 41

Tx chronic Hepatitis

Back 41

Adefovir dipivoxil, alpha interferon, lamivudine

Front 42

How can you prevent Hep. B?

Back 42

Avoidance
Passive immunization (with specific high titer Hep B Ig)
Vaccine (HBsAg subunit, produced by recombinant DNA technology) - use with 12 hrs of birth to Hep. B positive mother

Front 43

How can Hep. B transmission from mother to child best be prevented?

Back 43

Screen mother's blood for HBsAg at first prenatal visit.
If positive, vaccinate intramuscularly with HBIG and Hep. B vaccine (at different sites) within 12 hours of birth

Front 44

What characterizes chronic Hep B?

Back 44

persistent hepatocyte necrosis and hepatic inflammation

Front 45

Is chronic Hep B always anti-HBe positive?

Back 45

No, chronic Hep B is divided into anti-HBe positive and anti-HBe negative (but usually anti-HBe positive) types, with the anti-HBe positive type being the less infectious

Front 46

What characterizes an asx HBV carrier?

Back 46

persistence of HBsAg in bloodstream
no detectable hepatocyte necrosis or hepatic inflammation

Front 47

What characterizes resolved Hep. B?

Back 47

previous HBV infection without significant virological, biochemical or histological evidence of persistent infection.
positive for anti-HBs and anti-HBc

Front 48

What constitutes an acute exacerbation of chronic Hep B?

Back 48

increase in serum levels of hepatocellular enzymes to more than 10x the upper limit of normal and more than twice baseline.
may reflect Hep D superinfection

Front 49

What consititutes a reactivation of Hep B?

Back 49

reappearance of active hepatocyte necrosis and hepatic inflammation in a person with previous infection followed by asx carrier or resolved status

Front 50

What is the natural host of Hep. B?

Back 50

Humans

Front 51

What is a Dane particle?

Back 51

42nm diameter infectious Hep. B virion
28nm core containing DNA and DNA polymerase surrounded by layers of HBsAg

Front 52

How does Hep. B replicate?

Back 52

complex cycle!
core is assembled in nucleus of infected cell and moves into cytoplasm where it acquires its coat of HBsAg (as well as glycosylated and unglycosylated preS1 and preS2 polypeptides, precursors to HBsAg that facilitate binding to hepatocyte membranes)

Front 53

Do 22nm spherical and filamentous Hep. B particles contain preS1 and preS2?

Back 53

No, only HBsAg

Front 54

How many serotypes does Hep. B have?

Back 54

1 dominant neutralizing epitope (Abs against one strain will protect against all strains, as well as Hep. D)
BUT multiple serotypes resulting from variations in 2 minor epitopes

Front 55

Hep. D virus:
+/- ss/ds RNA/DNA
icosahedral/helical
enveloped/naked

Back 55

defective - ss circular RNA
outer lipoprotein layer composed of HBsAg (therefore requires HBV to replicate)

Front 56

How is Hep. D transmitted?

Back 56

Percutaneous (most efficiently)
Sexual
RARE- perinatal

Front 57

What dzs does HBD cause?

Back 57

severe or fulminant acute hepatitis
chronic hepatitis
Co-infection with HBV causes more severe/acute dz with higher risk of fulminant dz, lower risk that HDV will become chronic

Front 58

Which part of the meninges is infected in meningitis?

Back 58

CSF in subarachnoid space

Front 59

Which sources do the organisms causing meningitis come from?

Back 59

Most frequently, blood-borne organisms. Occasionally due to direct spread from infected inner ear, infected sinuses, or basilar skull fractures that break the integrity of the meninges.

Front 60

Requirements of bacteria that cause meningitis

Back 60

colonize mucosal epithel. (adhesins), invade and survive intravascularly (capsules evade complement), cross BBB (pili), survive in CSF, cause inflammation (LPS or PDG)

Front 61

Which bacterial products cause inflammation (associated with meningitis)?

Back 61

LPS (Gram negatives) and PDG (Gram positives)

Front 62

Which compounds elicit cytokine responses when injected into CSF?

Back 62

TNF, IL-1, TL-6, IL-8

Front 63

Antibody to which compounds protects against meningitis?

Back 63

TNF, IL-1

Front 64

How does meningitis cause brain damage?

Back 64

Inflammation in subarachnoid space increases pressure, compresses vessels (decreasing blood flow), and bacterial and WBC toxins cause damage

Front 65

What ligand do endothelial cells use to respond to LPS and PDG on the blood side of the BBB?

Back 65

CD14 (absorb it from plasma)

Front 66

Why doesn't the immune system function in CSF?

Back 66

CSF has low levels of Abs and complement, and the liquid environment makes phagocytosis inefficient, allowing rapid bacterial multiplication

Front 67

What age group is primarily affected by bacterial meningitis?

Back 67

Birth- children. Newborns because the BBB is not well developed, and because of head trauma associated with birth

Front 68

What are common causes of meningitis in newborns?

Back 68

Listeria monocytogenes, Group B Strep, E. coli (especially capsular type K1)

Front 69

What are common causes of meningitis in the young?

Back 69

Haemophilus influenzae, Neisseria meningitidis

Front 70

Describe the first phase of neutrophil exudation into CSF and BBB breakdown

Back 70

Bacteria in CSF induce IL-1 and TNF release, which cause the rapid, transient expression of selectins (ELAM-1 ) and generation of thrombin (which induces CD62, another selectin). TNF acts on the neutrophil to increase the affinity of LAM-1 for its receptor on the endothelial cell.

Front 71

Describe the second phase of neutrophil exudation into CSF and BBB breakdown

Back 71

Prolonged cytokine exposure causes the endothel to release IL-8, which cleaves LAM-1 and increases beta2 CD18 integrins on neutros and inhibits ELAM binding. Other cytokines cause endothel expression of ICAM-1, leading to diapedesis.

Front 72

Describe the third phase of neutrophil exudation into CSF and BBB breakdown

Back 72

Local inflamm cytokines activate neutros in CSF to release vasoactive lipid autocoids (PAF, LTs, PGs) and toxic O2 species to impair BBB: endothel slowly takes up macromolecules via vesicles, and there is paracellular leakage through open intercellular junctions of venules.

Front 73

Which species of bacteria cause meningitis?

Back 73

Strep pneumo, Neisseria meningitis, H.flu, Staph aureus and Listeria monocytogenes

Front 74

What age group is affected by Strep pneumo meningitis?

Back 74

All ages groups, including adults since Abs to one capsular tpye is not protective against other types

Front 75

What increases risk of severe Strep pneumo bacteremia and meningitis?

Back 75

Splenectomy, alcoholism and hypogammaglobulinemia

Front 76

What types of infection with Strep pneumo lead to bacteremia?

Back 76

nasopharyngeal colonization alone or pneumococcal pneumonia

Front 77

What is the second most common organism causing bacterial meningitis?

Back 77

Neisseria meningitis

Front 78

What age group is primarily affected by Neisseria meningitis?

Back 78

children and young adults

Front 79

Which capsular groups of Neisseria meningitis are responsible for epidemic disease?

Back 79

Groups A and C

Front 80

Which capsular groups of Neisseria meningitis are responsible for sporadic disease?

Back 80

Group B

Front 81

Does Neisseria meningitis ever occur with meningococcal shock?

Back 81

Yes, it can occur with or without it.

Front 82

What age group is primarily affected with Haemophilus influenzae meningitis?

Back 82

Unimmunized children >3 months and <6 years (lack Abs!)

Front 83

Which capsular type of Haemophilus influenzae causes meningitis?

Back 83

Type B

Front 84

How commonly is Staph aureus the cause of meningitis among adults?

Back 84

9-10% (but this is still uncommon given the high frequency of staph bacteremia!)

Front 85

What populations are susceptible to Listeria monocytogenes meningitis?

Back 85

Neonates, pregnant women, immunosuppressed patients (elderly, cancer) and alcoholics

Front 86

Meningitis sx (adults)

Back 86

Headache, fever, stiff neck

Front 87

Meningitis sx (infants/children)

Back 87

irritability, vomiting, poor feeding, fever

Front 88

Are localizing neurologic signs and coma common sx of meningitis?

Back 88

Inflammation is global so focal signs are uncommon, but coma is possible in severe infection (and it is a poor prognostic sign)

Front 89

What is the characterisitic sx of meningitis?

Back 89

Stiff neck (resists flexion at the nexk more than rotation) - not so much in infants or comatose patients

Front 90

Bacterial Meningitis dx

Back 90

CSF exam: 5<x<100 cells (>80% of them polys), organisms visualized on Gram stain (10^5 needed), >60mg protein (influx from serum), low CSF glucose (<40% of serum glucose, due to depressed transport at choroid plexus), positive culture

Front 91

Bacterial Meningitis tx

Back 91

QUICKLY start antibiotics (PCN or Ceftriaxone, both of which achieve appreciable CSF concentrations and are effective against most likely organisms). If resistant to these, treat with vancomycin (only crosses inflamed meninges)

Front 92

Prognosis of bacterial meningitis

Back 92

15% fatality rate (cerebral edema, seizures, overwhelming bacteremia- esp. N. meningitis), half of survivors have neurologic sequelae (if children, deficits often insidious onset)

Front 93

How does the fungi causing meningitis enter the CSF?

Back 93

portal of entry = lungs, then enters CSF via blood. However, meninges may be only site infected (so lack of disseminated dz does not exclude dx)

Front 94

Which species of fungi cause meningitis?

Back 94

Cryptococcus neoformans and Coccidioides immitis

Front 95

How does the inflammatory response to fungal meningitis differ from bacterial meningitis?

Back 95

Fungal meningitis causes a chronic rather than acute inflammatory response, and organisms localize to base of brain causing basilar meningitis

Front 96

Where in the brain do fungi causing meningitis localize?

Back 96

base of brain, causing basilar meningitis and often obstructive hydrocephalus

Front 97

If fungal meningitis is found in an un-immunocompromised patient, which species is it likely to be?

Back 97

Coccidioides immitis. Nowadays, 95% of Crypto meningitis cases are immunocompromised

Front 98

Where is Coccidiodes immitis found in the US?

Back 98

Desert southwest (as arthroconidia in soil, become spherules in tissue)

Front 99

What are the most common sites of dissemination of Coccidioides immitis?

Back 99

Meninges, bone, skin

Front 100

Fungal meningitis sx

Back 100

gradual onset of HA, with or w/o fever. If also hydrocephalus: N/V, cranial nerve defects.

Front 101

Which type of fungal meningitis presents often with the meninges as the only infected site?

Back 101

Coccidioides immitis. Also possible with Crypto, but Crypto often presents with pulmonary involvement or fungemia

Front 102

Fungal meningitis dx

Back 102

CSF exam: 50-500 cells, predominantly lymphs, increased protein, low glucose. Tests for Cryptococcal Ag and C. immitus Ab (esp. impt since difficult to culture organisms trapped in basilar meninges)

Front 103

How do you distinguish fungal from bacterial meningitis on CSF exam?

Back 103

Fungal meningistis has a moderate number of cells (5-500 as opposed to 5-100), a predominance of lymphocytes as opposed to polys, and a negative bacterial culture

Front 104

What causes syphilis?

Back 104

Treponema pallidum

Front 105

Describe Treponema pallidum's structure

Back 105

Spirochete
endoflagella (axial fibrils) attached at each end between the cytoplasmic and the outer membrane.
layers around cytoplasm: trilaminar membrane, PDG layer, periplast, inner mucopeptide layer, outer lipoprotein membrane, PL-rich outer membrane lacking traditional LPS

Front 106

Where can Treponema pallidum be cultured?

Back 106

Not in vitro, but can be cultivated in rabbit testes, or 7 days at 35 degrees or 48 hours at 37 degrees in special media. Viable after being frozen at -70 degrees.

Front 107

How is Treponema pallidum transmitted?

Back 107

sexual or congenital, rarely by skin contact or transfusion.
Cheifly affects sexually active people (age 15-50)

Front 108

Is syphilis zoonotic?

Back 108

No, humans are the only natural hosts of Treponema pallidum

Front 109

How does primary syphilis present?

Back 109

after ~21 day incubation, hard, painless, shallow chancre on penis, labia, perianal, mouth. resolves in 2-8 weeks (longer in immunocompromised)
regional lymphadenopathy is common

Front 110

What is the likelihood that a patient with primary vs. secondary vs. tertiary syphilis tests positive on nontreponemal (reagenic) tests or specific treponemal tests?

Back 110

primary:
nontreponemal - 70-80%
treponemal - 50-85%
secondary:
nontreponemal - 99%
treponmal - 97-100%
tertiary:
nontreponemal - 60-98%
treponemal - 97-100%

Front 111

How does secondary syphilis present?

Back 111

2-12 weeks post infection, copper-colored maculopapular rash on palms and soles, fever, lymphadenopathy, condylomata lata, meningitis, hepatitis, potentially glomerulonephritis or patchy alopecia.
resolves spontaneously, but may recur up to 4 years later

Front 112

How does tertiary syphilis present?

Back 112

1-30 years after infection
-Cardiovascular (endarteritis of vaso vasorum leading to aneurysm formation, often of ascending aorta)
-Gummatous (eroding lesions of skin and bone. granulomas with amorphous center and small vessel endarteritis.)
-Neurological syphilis: meningovascular (stroke/seizure 5-12 years later due to infarction) or parenchymatous (general paresis or Tabes dorsalis)

Hint 112

years after infection
-cardio
-gummatous
-neurological - 2 types

Front 113

What is the classic pathology seen in all stages of syphilis?

Back 113

obliterative endarteritis

Front 114

Syphilis dx

Back 114

Best choice: serology.
direct visualization of organism (best seen in dark-field microscopy, performed soon after it is taken), or
direct fluorescent Ab testing (DFA-TP)

Front 115

Describe the general paresis associated with tertiary syphilis

Back 115

occurring 15-20 years after infection.
dementia with confabulation, slurred speech, Argyll-Robertson pupils.

Front 116

What is tabes dorsalis?

Back 116

form of parenchymatous syphilis (one of the neurological manifestations of tertiary syphilis).
lightning pain, wide gait, loss of deep pain/temp/position/vibration sense, Argyll-Robertson pupils, positive Romberg.
caused by demyelinization of dorsal roots, dorsal root ganglia and posterior columns

Front 117

What are Argyll-Robertson pupils?

Back 117

pupils will accomodate, but don't react.
a sign of tertiary neurological syphilis.

Front 118

What do nontreponemal tests screen for? Name examples

Back 118

screen for Wasserman Abs (IgG and IgM Abs to cardiolipin-cholesterol-lecithin Ag). Best for dx of secondary syphilis.
Not specific to syphilis, also seen in pregnancy, collagen vascular dz, Lyme dz, measles. Only present during active dz.
VDRL (venereal dz research lab)
RPR (rapid plasma reagin)
ART, TRUST

Front 119

What do specific treponemal tests screen for? Name examples

Back 119

screen for Abs to Treponema Ags.
More complex than nontreponemal tests!
Best for dx of secondary and tertiary syphilis.
Can give false positive for other spirocheta illnesses.
May revert to negative if effective treatment is given early.
Fluorescent Treponemal Ab Absorption (FTA-ABS)
Microhemagglutination test (MHA-TP)
TPHA, ELISA

Front 120

Syphilis tx

Back 120

PCN G admin parenterally.
prep, dosage and length of tx depend on stage and clinical manifestations

Front 121

What causes Yaws or frambesia?

Back 121

Treponema pertenue

Front 122

Describe Yaws

Back 122

<15 yo in tropical regions,
transmitted through close contact or insects
ulcerating lesion (mother yaw) at site of infection.
6-12 weeks later, untreated, more ulcerating lesions appear with ability to penetrate bones and cause chronic disfigurement and disability.
tx: PCN at first or second stage

Front 123

What causes Pinta or Mal de Pinto?

Back 123

Treponema carateum

Front 124

Describe Pinta or Mal de Pinto

Back 124

southern Mexico, Central America and Columbia
transmitted via contact of broken skin with a lesion.
Lesions start as small, erythematous itchy papules. Those coalesce and leave hypopigmentation after resolving (possibly years later).
3-12 months later and recurring for up to 10 years, "pintids" (brown, blue or gray lesions) appear in same areas.
does not affect general health, can be disfiguring

Front 125

What causes Bejel/endemic syphilis?

Back 125

Treponema pallidum (subspecies pallidum) - same as regular syphilis, just limited to Africa and Western Asia and transmitted nonvenereally

Front 126

What kinds of lice are there and how are they different?

Back 126

-Head louse (Pediculus humanus var capitus). spread by contact/shared stuff. epidemic among schoolchildren.
-Body louse (genus Pediculus humans var corporis) on clothing of those with poor hygiene, during war or famine.
-Pubic louse (genus Phthirus pubis) spread by sexual/close body contact. may also infect scalp, eyelashes, eyebrows and axilla

Front 127

Life cycle of Lice

Back 127

Nits (eggs) laid in hair/clothes,
hatch into nymphs in 7-10 days, nymphs must feed w/in 24 hours.
2-3 weeks and 3 molts later, nymphs become adults
Adults live 20-30 days.
Females lay 250-300 eggs in a lifetime

Front 128

Clinical manifestations of lice

Back 128

Pruritis (hypersensitivity rxn to lice saliva Ags)
Red macules and papules with excoriations, nits are visible.
Crabs (pubic louse): maculae cerulae

Front 129

What are maculae cerulae?

Back 129

seen in crabs (Phthirus pubis)
<1 cm grey/blue flat lesions on trunk and thighs.
caused by anticoagulant injected by the louse's bite.

Front 130

The body louse transmits:

Back 130

epidemic typhus (Rickettsia prowazekii),
trench fever (Rochalimaea quintana),
relapsing fever (Borrelia recurrentis)

Front 131

Lice tx

Back 131

if body louse, new clothes.
If head or pubic louse:
1% lindane, gamma benzene hexachloride (Kwell), or
pyrethrin liquid with piperonyl butoxide (Rid), or
1% permethrin creme rinse (Nix), or
0.5% malathion lotion (Prioderm).
Vinegar and water remove nits

Front 132

Life cycle of scabies

Back 132

17 days long
adult female: 0.35mm long, round with 8 short stubby legs. lays 2-3 eggs/day in a burrow (elicits hypersensitivity reaction).
Larvae emerge 84-92 hours later (3-4 days), become adults and mate. males die, females live 4-6 weeks

Front 133

How is scabies transmitted?

Back 133

intimate contact.
pregnant females can live off hosts for up to 2 days

Front 134

Scabies sx

Back 134

dependent on host hygiene
typically itchy interdigital web spaces, belt line, axillae, penis, ankles

Front 135

Scabies tx

Back 135

1% lindane or 5% permethrin.
also treat the infected person's contacts, and wash bed linens/clothes used for the last 3 days

Front 136

What is Norwegian scabies and how do you tx it?

Back 136

more severe form of scabies in immunocompromised, presents with widespread, hyperkeratotic, crushed cutaneous lesions.
isolate infected people immediately and tx: ivermectin

Front 137

What classes are lice and scabies in?

Back 137

Phylum Arthropoda
Lice in Class insecta (6 legs)
Scabies in Class Arachnida (8 legs), Sarcoptes scabiei var hominis

Front 138

Diarrhea epidemiology

Back 138

leading cause of infant mortality in underdeveloped world.
underdeveloped: transmitted via fecal contamination of water, food, or person-to-person spread.
developed countries: transmitted via food (animals to people) and can be epidemic "food poisoning"

Front 139

Def'n of diarrhea

Back 139

3+ loose/watery stools in 24 hours

Front 140

What are the types of diarrhea?

Back 140

Toxigenic: arising from enterotoxins from bacteria that promote fluid secretion but not mucosal damage. Pain in mid abdomen
Invasive/Dystentery: bloody/mucusy stools accompanied by tenesmus due to ulcerations of colonic mucosa (direct invasion by pathogens or cytotoxin). Pain in lower abdomen and rectum.
Food poisoning: caused by eating contaminated food (can be gastroenteritis or botulism or mushroom poisoning)

Front 141

What are host defenses against diarrhea?

Back 141

"My Intestines Fend (off) Adverse Pathogens": Motility, Immunity, Flora, Age (middle-age), pH (low pH in stomach- Shigella is most resistent and only 100 organisms req'd for diarrhea)

Front 142

Which organisms cause "gastroenteritis" in stomach?

Back 142

H. pylori causes gastritis and P.U.D. (not classified as gastronenteritis)

Front 143

Which organisms cause gastroenteritis in the small intestine?

Back 143

-usually a secretory diarrhea
ETEC, EPEC, Vibrio cholerae/parahaemolyticus, Salmonella, Campylobacter jejuni, Yersinia
E.coli species: "TP for secretory diarrhea"

Front 144

Which organisms cause gastroenteritis in the large intestine?

Back 144

- usually dysentery (diarrhea with blood and pus b/c colonic mucosa destroyed)
Shigella, EIEC, EHEC, Salmonella, Campylobacter, Clostridium difficile
E.coli species: "Diarrhea with HI blood/pus content"

Front 145

Describe Shigella gastroenteritis

Back 145

children
transmitted fecal/oral or by flies
short incubation period
biphasic dz: fever + watery diarrhea followed by dysentery (30-50%)
dx by culture
tx: none, or 1st line fluoroquinolones if severe

Front 146

Other dzs caused by Shigella (as well as EHEC)

Back 146

TPP in adults
HUS in children

both caused by effects of Shiga toxin and Shiga-like toxin (SLT) on endothelial cells

Front 147

How does Shiga toxin work?

Back 147

2 component toxin:
B subunits bind globotriaosyl ceramide (Gb3) on cell membranes [Note: also on B lymphocytes]
A subunit internalized, inhibits protein synth by cleaving 28S rRNA. This prevents EF-dependent binding of tRNA to ribosomes.

Front 148

What is encoded by Shigella's large plasmid?

Back 148

Factors for invasion and spread.
Invasion genes are coordinately expressed at 37 degrees C, and regulated by a sensory system requiring ompB (porin regulating gene)
Spread genes: enters cell basolaterally using Peyer's patches, PMNs and Type III secretion systems, then spreads laterally via cytoplasmic actin tails.

Front 149

What is EAEC?

Back 149

Enteroaggregative E. coli
2nd most common cause of traveler's diarrhea.
causes persistent diarrhea in AIDS.
plasmid-encoded toxin is a serine protease.

Front 150

Describe EPEC

Back 150

Enteropathogenic E. coli
infants, nosocomial and community infections
Dx via Abs to O Ags (only a few possible)
-adhere to and efface microvilli (ePec Pushes microvilli down)
Tx: ABX can shorten dz course, though it shows widespread resistance

Front 151

How does EPEC efface microvilli?

Back 151

chromosomal genes mediate loose adherence.
cell contact induces Type III secretion system and bacteria secrete Tir (receptor for intimin- an OMP) that inserts into host cell membrane.
Tir binds intimin, causing host actin to rearrange under bacteria, transforming microvilli into only an actin pedestal. This decreases nutrient absorption surface area.
Plasmid-encoded bundle-forming pili (BFP) allow bacteria to cluster on cell. Calcium flux activates calcium channels, causing electrolyte and water loss.
Genes activating cellular kinases are also important (?)

Front 152

What is CFA?

Back 152

virulence factor of most ETEC
hemagglutinating fimbriae, 3 types
allow bacteria to attach to epithelial cells in small intestine.

Front 153

If LT toxin and cholera toxin share 80% homology, why is dz from LT toxin not as severe as cholera?

Back 153

LT toxin is not secreted, and requires host cell proteases to cleave it for it to become active

Front 154

Why is infant ETEC more severe than adult ETEC?

Back 154

Infants have more guanylin receptors, so get more effect from ST toxin

Front 155

Describe EHEC

Back 155

Enterohemorrhagic E. coli. O157:H7 most common serotype - and can be differentiated b/c it doesn't ferment sorbitol
Transmitted via ingesting uncooked chopped beef (part of normal bovine intestinal flora) or fecally contaminated food (Jack in the box outbreak).
virulence factors: SLT, adherence genes, intimin (for adherence, not invasion)
range from watery diarrhea to frank hemorrhage, later complications: TPP, HUS.

Front 156

Taxonomy of Salmonella

Back 156

2 species: S. bangori (environmental) and S. enterica (humans).
O and H Ags allow further serological division (ex. S. typhi, S. paratyphi)

Front 157

Dzs caused by Salmonella

Back 157

acquired via contaminated food, water, or contact with animals
-Typhoid fever

Front 158

Describe typhoid fever

Back 158

caused by Salmonella typhi and paratyphi
enter via gut, spread and multiply via RES, cause 4 week febrile illness (with little or no diarrhea), then chronic carrier state in gall bladder.
dx: early by b.m. or blood culture
late by stool culture
tx: chloramphenicol, fluoroquinolones, trimethoprim/sulfa

Front 159

Describe Salmonella gastroenteritis

Back 159

in anaerobic conditions, a type III secretion system invades ileum and injects tyrosine kinase (phosphorylates Cdc42 causing actin polymerization and cell membrane ruffles) and tyrosine phosphatase (inactivates Cdc42 to return membrane to normal), enters cells and sits in vacuoles for binary fission, pass through to submucosa without damaging cells. Invaded cells secrete IL-8 and their tyrosine kinases are activated, inducing inflammation. use M cells to enter Peyer's patches
Reiter's syndrome (reactive arthritis, redness of the eyes and urinary tract signs) may be complication.
dx: stool culture
tx: only elderly, infants or immunocompromised

Front 160

Describe Salmonella septicemia

Back 160

caused by S. choleraesius and S. dublin most often, less often S. enteritidis and S. typhimurium.
immunocompromised (since CD4 cells req'd to fight infection) or extremes of age.
has virulence plasmids encoding genes that promote growth in macrophages (most impt. one targets actin through ADP-ribosylation)
dx: culture
tx: same as typhoid: chloramphenicol, fluoroquinolones, trimethoprim/sulfa

Front 161

Describe Yersinia gastroenteritis

Back 161

Yersinia enterocolitica (most likely) or pseudotuberculosis.
cold climates, pigs are reservoir.
facultative intracellular: enters via "invasin" binding to beta1 integrins with high affinity. plasmid responds to low Ca2+ in vacuoles and contact with eukaryotic cells, causing synthesis of Yops and V Ags
Yops: type III secretion system, injects 1) protease that removes an AA from Rho, releasing it from host membrane and 2) potent tyrosine phosphatase.
invades Peyer's patches

Front 162

Describe Campylobacter jejuni and coli gastroenteritis

Back 162

clinical presentation identical to Salmonella (bloody, self-limited diarrhea, worse in immunocompromised b/c CD4s impt. in host defense.
rarely cause bacteremia because they are sensitive to serum killing
-C. jejuni makes cytolethal distending toxin (just like E. coli and Salmonella) that is a ssDNAse leading to nuclear fragmentation and cell cycle arrest!
dx: stool culture

Front 163

Review Campylobacter facts

Back 163

small, curved, Gram - rods
polar flagella
oxidase +, microaerophilic (5-10%), capnophilic (4-8%), ferment peptones, not carbohydrates.
differentiated from H. pylori only by urease test (H. pylori is urease +)

Front 164

Describe Vibrio cholera gastroenteritis

Back 164

Gram -, comma-shaped free-living aquatic organism, acquired via contaminated food and water.
all cases are serotype O1 (latest was O139).
virulence factors: CTX element (phage encoded cassette of virulence genes inserted into chromosome during lysogeny- encodes cholera toxin and CTX),
Cholera toxin's secretion is coordinately reg. by temp and ionic concentration.
CTX - 2 component toxin irreversibly poisons host's adenyl cyclase resulting in high cAMP levels
ZOT - zonula occludens toxin, destroys TJs
Ace - accessory cholera enterotoxin
tx: IV or PO rehydration. Tetracycline can reduce dz length

Front 165

Clostridium perfringens Enterotoxin type A gastroenteritis

Back 165

acute (8-16 hours), self-limited food poisoning
no fever nor vomiting
enterotoxin is heat-labile and activated by trypsin
ingested in meat that has been cooked, but spores were not killed, so they grew and released the enterotoxin (which binds brush border receptors and interrupt ion exchange)

Front 166

Beta toxin- Clostridium perfringens type C gastroenteritis

Back 166

causes enteritis necroticans
sx: ab pain, vomiting, diarrhea, patchy necrosis of upper small intestine (potentially obstruction and fatal)
occurs in people with low protein diets (or sweet potato-rich diets that contain trypsin inhibitors - New Guinea) that eat a large meat meal and can't digest it properly because of downregulated intestinal proteases.
called "pigbel" in New Guinea

Front 167

Staphylococcal Enterotoxin gastroenteritis

Back 167

acute (1-6 hour) food poisoning
sx: vomiting and diarrhea
mech: acts on neural receptors in upper GI tract, stimulating vomiting center.
Heat Stable!! several types, named A through E, with 3 subtypes of C. some are encoded on bacterial phages

Front 168

Bacillus cereus gastroenteritis

Back 168

2 types, both self-limited:
1) Chinese Restaurant: boiled rice cooled (with spores still intact), made into fried rice next day, ingested. 1-6 hours later, vomiting!
2) Contaminated meat or veggies causing abdominal pain, watery diarrhea and nausea 10-12 hours after ingestion

Front 169

Clostridium difficile gastroenteritis

Back 169

post antibiotic use (esp. PCN, cephalosporin and clindamycin)
two toxins - enterotoxin A and cytotoxin B - required, they bind to receptors on intestinal epithelial cells, glucosylate Rho proteins and disrupt focal adhesions between cells (causing massive fluid secretion/diarrhea) and acute inflammatory infiltrate.
tx: d/c ABX, metronidazole, PO vancomycin

Front 170

What virus family does Hep. C belong to?

Back 170

Flaviviridae (same as yellow fever)

Front 171

Hep. C virus
+/- ss/ds DNA/RNA
icosahedral/helical
enveloped/naked

Back 171

+ ss RNA
icosahedral
enveloped

Front 172

How many serotypes are there for Hep. C?

Back 172

In each infected person there are many closely related but distinct genetic sequences.
6 major genotypes or clades, with >60% nucleotide sequence identity
Types only differ in geographic distribution and response to inferferon treatment
1a and 1b = USA, worse response to interferon
2, 3 = good response to inferferon
4 = Africa and Middle East

Front 173

What % of US adults are seropositive for Hep. C?

Back 173

0.5-1%

Front 174

How is Hep. C transmitted?

Back 174

Parenterally
-percutaneous (major cause of post-transfusion hepatitis, though current risk is very low. health care workers actually have a lower prevalence than general population)
-Perinatal (6%, 17% if also HIV+)
-Sexual (low efficiency, male to female more efficient)

Front 175

Where does Hep C virus replicate?

Back 175

in cytoplasm,
does not grow in tissue culture

Front 176

Dzs caused by Hep. C virus

Back 176

acute hepatitis (mild, only 20% jaundiced)
*chronic hepatitis (10-70%) -mostly asx
cirrhosis (<5-20%)
mortality from chronic liver dz in 1-5%

*Great variability in progression. Risk factors for progressive/severe chronic dz: alcohol, >40yo at infection, HIV coinfection, male

Front 177

How long is Hep. C's incubation period?,

Back 177

6-7 weeks (range 2-26 weeks)

Front 178

What family of viruses is Hep. E virus from?

Back 178

Family Calciviridae,
though so much different that may be in its own family of HEV-like viruses

Front 179

Hep. E virus
+/- ss/ds RNA/DNA
icosahedral/helical
enveloped/naked

Back 179

+ssRNA
icosahedral
naked

Front 180

How is Hep. E transmitted?

Back 180

Enterically
fecally contaminated drinking water (minimal person-to-person transmission).
Avoid drinking water, eating shellfish, and eating uncooked fruits/veggies in endemic areas.
*Vaccine from Western countries does not prevent infection!

Front 181

Dzs caused by Hep. E

Back 181

acute hepatitis (dz worse with increasing age)

-fatality is 1-3%, 15-25% in pregnant women, esp. in 3rd trimester.

Front 182

How does Hep. E replicate?

Back 182

In cytoplasm,
does not replicate in tissue culture

Front 183

How long is Hep. E's incubation period?

Back 183

40 days (range 15-60 days)

Front 184

Proteins encoded by Rabies genome

Back 184

5 proteins:
L - viral transcriptase
N - nucleocapsid protein, complexed with RNA (varies by region)
P (or NS) - phosphoprotein associated with its RNA
M - matrix protein found on inner side of envelope
G - glycoprotein makes spike-like projections on surface (varies by region)

Front 185

Receptors for Rabies virus

Back 185

nAChR
NCAM
p75NTR

Front 186

Rabies epidemiology

Back 186

primarily dz of animals (bats, dogs, skunk, fox, raccoon), though vector differs by geographical location.
Mammals are generally susceptible, with foxes, coyotes and wolves having the highest susceptibility, skunks, raccooons and bats medium susceptibility, and rats, rabbits and squirrels low susceptibility.
Suceptibility det by virus strain, genetic background, # receptors in SKM, inoculum size, degree of innervation at site, CNS proximity.

Front 187

Rabies nat'l hx

Back 187

G protein mediates attachment to host cell membrane receptor.
large doses immediately enter unmyelinated peripheral nerves, small doses replicate in SKM before entering.
Retrograde axonal spread to spinal cord (sx: pain or paresthesia at wound site). Incubation 5 days- 1 year.
Brain (sx: encephalitis with neuro symptoms, incl. hyperaggression, hypersalivation and hydrophobia)
Death within days of sx onset

Front 188

Rabies dx

Back 188

-Negri bodies (eosinophilic cytoplasmic inclusions) in brain via LM or IF
-skin biopsy + for Ag

Front 189

Preventing Rabies in animals

Back 189

leash laws, control strays
mandatory vaccination
Europe: oral vaccine by aircrafy
Venezuela: vaseline and coumadin rubbed on cows to kill bat colonies

Front 190

Rabies risk

Back 190

after bite: 5-80%
after scratch: 0.1-1%
possible via respiratory exposure in bat caves, inhalation in a laboratory, and corneal transplants

Front 191

Rabies prevention

Back 191

vaccinate people with high occupational risk (veterinarians, animal handlers, lab workers)
Post exposure protocol:
-wash with soap/water
-inject anti-rabies Igs in 1 deltoid and simultaneously vaccine in other deltoid. continue 4 more vaccine doses at 3, 7, 14 and 28 days post-exposure. never inject in gluteal region, use anterolateral thigh in kids if needed

Front 192

Rabies virus:
family
+/- ss/ds RNA/DNA
enveloped/naked

Back 192

Rhabdoviridae
-ssRNA
enveloped and "bullet-shaped"

Front 193

Define aseptic meningitis vs. encephalitis vs. poliomyelitis (even though they are commonly overlapping)

Back 193

Aseptic meningitis: benign syndrome, HA, stiff neck, fever, CSF changes (pleocytosis with lymph predom, increased protein, normal sugar and negative culture).
Encephalitis: brain parenchymal involvement, depressed consciousness, seizures, focal neuro signs and increased intracranial pressure
Poliomyelitis: febrile illness with flaccid paralysis w/o sensory defect or cortical damage

Front 194

Viral meningitis vs. bacterial meningitis

Back 194

Viral more common, less severe (almost always complete recovery). Same sx: HA, fever, neck stiffness, viral may include vomiting and/or photophobia

Front 195

CSF in viral meningitis

Back 195

clear, slightly increased opening pressure, moderate pleocytosis, lymphocytes predominate after first day, normal protein and glucose

Front 196

Viruses commonly causing meningitis

Back 196

Enteroviruses (summer and autumn, accompanying rash)
Mumps (winter and spring)
Lymphocytic Choriomeningitis - LCM (winter and spring)
HSV (any season)

Front 197

LCM Meningitis transmission

Back 197

by house mouse, Mus musculus (shedded in urine, obtained by direct contact, inhaling particles or ingesting contaminated food)

Front 198

LCM sx

Back 198

Incubation 8-13 days
Biphasic febrile illness
intial phase: fever, malaise, HA, muscle aches, anorexia, N/V
second phase: a few days later, meningitis sx

Front 199

What is the only treatable cause of viral encephalitis?

Back 199

HSV: treat with acyclovir!

Front 200

What are permanent sequelae of viral encephalitis survivors?

Back 200

mental retardation, epilepsy, blindness, deafness

Front 201

Viruses that cause encephalitis

Back 201

-arthropod borne agents (Togaviruses, Flaviviruses, Bunyaviruses) in summer and autumn
-HSV (any season)
-Mumps (winter and spring) - usually complete recovery
-Measles (winter and spring) - 10% mortality, 60% morbidity
-VZV (winter and spring)
-Rabies

Front 202

Which causes of viral encephalitis have available vaccines?

Back 202

Mumps, measles, VZV

Front 203

Retroviridae
+/- ss/ds DNA/RNA
enveloped/naked

Back 203

+ssRNA (2 copies, so pseudo-diploid, allows for recombination)
enveloped

Front 204

Genes in simple retrovirus genome

Back 204

gag- internal core proteins (p24 protein conical core, p7 acts on 5' end of RNA to package genome into capsid)
pol- RT, integrase, protease
env- surface glycoprotein (gp120/41, mediates attachment and fusion)

(complex retroviruses have these as well as regulatory/accessory genes)

Front 205

Which Retroviridae infect humans?

Back 205

Out of 7 genera, only 3 infect humans
-Lentiviruses (HIV-1 and HIV-2)
-HTLV-BLV group
-Spumavirus ("foamy" viruses not yet proven to cause dz in humans)

Front 206

HIV-2 (vs. HIV-1)

Back 206

HIV-2 is less prevalent (West Africa only) and less pathogenic than HIV-1.
non-nucleoside reverse transcriptase inhibitors are ineffective against HIV-2

Front 207

HTLV-1

Back 207

Human T cell lymphotropic virus type 1
found in Africa, Caribbean and Japan.
transmitted via blood
infects T cells, not cytolytic, causes adult T cell leukemia and tropical spastic paraparesis (demyelinating dz that causes spasticity and weakness)

Front 208

HTLV-2

Back 208

Human T cell lymphotropic virus type-2
"orphan" virus with no clearly associated human dz

Front 209

Lentiviruses

Back 209

complex retroviruses (incl. HIV-1 and -2)
transmitted by body fluids
cause chronic, persistent cytopathic (cell-killing) infection and can infect non-dividing cells
3 groups:
-primate (HIV-1, -2, SIV) - cause immunodef, wasting and encephalitis. Tropism for CD4+ T cells, macrophages and microglial cells
-Ungulate (dz in cows)
-Feline (FIV) - dz of domestic cats, causing immunodef, wasting and encephalitis. Potential vector for use in gene therapy

Front 210

A person in the tropics has spasticity and weakness. T cells are infected

Back 210

tropical spastic paraparesis
caused by HTLV-1

Front 211

Origin of HIV

Back 211

cross-species transfer of SIV (simian immunodef virus) many times over the past 50 years.
most likley SIV-cpz (chimpanzee) or SIV-sm (sooty mangabees)

Front 212

Genetic variants of HIV

Back 212

only vary on nucleic acid sequence, there are no distinct serotypes
-Group M (main) - clades A-J exist, Clade B most common in North America and Europe, clade C in overall pandemic
-Group O (outlier)
-Group N (non-M, non-O)

Front 213

HIV entry into cells depends on

Back 213

CD4 (primary receptor on cell)
CCR5 or CXCR4 (co-receptor on cell)
-CD4 binds gp120/41 on virus. gp120/41 undergoes conformational change and recruits co-receptor. gp41 is inserted into cell membrane and membrane fusion occurs

Front 214

HIV "accessory" genes: Vif

Back 214

targets apobec3G (cellular cytidine deaminase that normally induces destruction and hypermutation of viral reverse transcripts) for destruction by proteasome
"IF apobec3G tries to kill reverse transcripts, we'll send her to be killed instead"

Front 215

HIV "accessory" genes: Vpr

Back 215

ubiquitinizes proteins to arrest cell cycle in G2/M, which optimizes viral genome transcription. important for viral replication in macrophages
"P.R.: wait, stop in G2/M. Okay, the macrophage can replicate virus now."

Front 216

HIV "accessory" genes: Vpu

Back 216

targets CD4 for degradation by proteasome,
enables release of virions from cell (by counteracting BST-2, an inhibitor of virion-release induced by interferon)
"P.U.!: take out CD4 trash, get those virions out (block BST- bad smelling trash)"

Front 217

HIV "accessory" genes: Nef

Back 217

endocytoses CD4 from cell surface
decreases MHCI expression (evades adaptive CMI)
activates T cells (favorable viral replication environment)
"That's eNEF CD4 and MHCI"

Front 218

Which HIV accessory genes can be considered responses to cell innate defense?

Back 218

Vif, Vpu

Front 219

Functions of HIV's LTRs

Back 219

LTR = long terminal repeats
5' LTR: transcriptional control and initiation at U3/R boundary.
3' LTR: polyadenylation

Front 220

HIV life cycle

Back 220

-Attachment,
-fusion, entry,
-RT copies viral RNA into DNA (with many errors),
-"preintegration complex" of cDNA and integrase localizes to nucleus.
-Integration into host genome by integrase (preferring actively transcribed genes),
-transcriptional activation by Tat (Tat binds CycT and Cdk9, which localize to TAR RNA and allow RNA Pol II to elongate RNA)
-RNA processing and export (Rev)
-Accessory genes do their functions
-Virions assembled and bud (gag sequences bind ESCRT proteins- which usually form multi-vesicular bodies and perform membrane scission during cytokinesis)
-Maturation (protease processes Gag and Gag-Pol polyproteins, which are required for infectious activity)

Front 221

HIV drugs

Back 221

Block attachment/fusion/entry:
-CCR5 antagonists
-Fusion inhibitors (enfuvirtide, subq, comp. inhibitor of gp41 packing)
Block RT:
-NRTI (nucleoSide RT inhibitors): -ine + acabavir
-NNRTI (nevirapine, efavirenze, etravrine- allosteric RT inhibitors, resistance only 1 mutation away)
-NucleoTide RT inhibitors: tenofovir (doesn't require phosphorylation, well tolerated and potent)
Block integration: raltegravir (irreversibly binds integrase)
Block Protease; PIs (-vir)

Front 222

RTI side effects

Back 222

lactic acidosis due to inhibition of DNA Pol gamma and mitochondrial toxicity (esp. DDI, D4T)

Front 223

PI side effects

Back 223

lipodystrophy, GI upset, hyperlipidemia, glucose intolerance

Front 224

HIV Lab tests

Back 224

-ELISA - screen for host Abs. If +, confirm with:
-Western blot - tests for Abs to individual HIV proteins.
-CD4+ count: marker of immunological damage. Normal = 400-1200, <200 = AIDS.
- RNA viral load: A negative ELISA may occur in acute/primary HIV infection, but the RNA viral load will be positive (high levels >10^6 until adaptive immunity lowers it to 10^4 or 10^5 for an asx "clinical latency" period). Successful therapy makes viral load <50= undetectable after 4-6 months. Viral load best predictor of CD4 loss and HIV progression.

Front 225

Primary HIV infection presentation

Back 225

transmitted by body fluids (genital secretions, blood, intrauterine, intrapartum, breast milk),
-presents like mono (fever, swollen lymph nodes, fatigue, rash, aseptic meningitis), and the patient is highly infectious.
-to dx, ask about HIV risk behaviors, thorough PEX to check for rash, baseline HIV Ab test and HIV RNA test (dx- RNA PCR or HIV p24 Ag, even if serology ambivalent)
-refer to HIV specialist to educate, evaluate drug resistance, and start treatment (2NRTIs AND either PI or NNRTI)

Front 226

Who do you offer antiretroviral treatment to?

Back 226

-all patients with sx of HIV
-patients with HIV-1 related nephropathy and Hep. B or C co-infection
-patients with CD4<350/mL or viral load >55,000/mL

Front 227

Antiretroviral drug resistance testing

Back 227

-Genotypic methods: nucleotide sequence determination of virus, looking for mutations in RT or protease
-Phenotypic methods: measure viral replication in presence of range of drug concentrations

Front 228

Chronic "asymptomatic" HIV infection

Back 228

lasts an average of 10 years before AIDS diagnosed. clinically latent but not disease latent- virus continues to replicated and destroy lymphoid tissue.
Patient may experience night sweats, fatigue, diarrhea, herpes outbreaks, thrush or painless lymphadenopathy. Since B cells stimulated, hypergammaglobulinemia, autoAb production, and neurological manifestations may occur

Front 229

AIDS dx

Back 229

CD4 <200 cells/mL or
any of a set of AIDS-defining opportunistic infections, including:
-pulm or disseminated TB
-PCP
-Crypto diarrhea and meningitis
-Toxo encephalitis

Front 230

Advanced AIDS

Back 230

CD4<50
additional infections occur, sometimes with more than one pathogen (CMV retinitis or colitis, Crypto diarrhea, MAC, M. kansasii, Karposi's sarcoma/lymphoma), usual symptoms can become more prominent.
Death from organ damage (lungs, CNS, GI)

Front 231

Immunogenetic factors in HIV

Back 231

-Delta-32 deletion in CCR5:
homozygotes are unlikely to become infected when exposed to HIV, heterozygotes progress more slowly
-MHC-HLA types
HLA-B27 and HLA-DR6 progress more slowly, B*35-Cw*04 increases risk of progression

Front 232

Primary vs. Secondary Immunodeficiency

Back 232

Primary- inherited, rare
Secondary - acquired, more common
(ex. infection attacking immune system, malignancies, drug reactions)

Front 233

General characteristics of B cell/Humoral immunity immunodeficiencies

Back 233

onset btwn 6 mo-2 years
Decreased B cells and plasma cells with normal B cell precursors and No Abs to previously administered Ag
Hx of frequent/recurrent enteric or sinopulmonary infections with ENCAPSULATED bacteria.
Workup: quantitate IgG, IgA, IgM, T cells (should be elevated, with normal subsets and function)

Front 234

Bruton's agammaglobulinemia

Back 234

X-linked deficiency in B cell tyrosine kinase (blocks B cell maturation)
Males get recurrent pyogenic infections (otitis, sinusitis, conjunctivitis, pneumonia, pyoderma) initially occurring between 6-18 months
severe cases: chronic enteroviral meningoencephalitis, Sabin-vaccine-associated paralytic polio

Front 235

Common Variable Immunodeficiency (CVID)

Back 235

most prevalent immunodeficiency dz.
bimodal incidence (peak at 25-45 yo, another at 5-15 yo), with sporadic inheritance
diagnosis of exclusion: heterogeneous group of disorders involving impaired Ab responses due to insufficient B cell activation.
recurrent pyogenic sinopulmonary infections, low IgG and IgA, 50% also low IgM

Front 236

Transient hypogammaglobulinemia of infancy (THI)

Back 236

decreased levels of IgG and IgA until 2-6 yo (At which point the levels reach reference ranges).
most likely due to a delay in development of effective T cell helper function

Front 237

Selective immunoglobulin deficiency

Back 237

IgA def: B cells with IgA on their surface are present but developmentally blocked. common amongst Caucasians
IgG subclass def: relative lack of one IgG subclass but normal total IgG. Usually asx

Front 238

General characteristics of T cell/Combined Immunodeficiencies

Back 238

recurrent/persistent viral infections and disseminated fungal infections
-can't produce IgG, IgA or IgE, but CAN produce IgM

Front 239

X-linked Hyper IgM syndrome (HIGM)

Back 239

X-linked mutation in CD40L, such that no class-switching nor memory-forming can occur.
Only IgM, no other Abs
-recurrent pyogenic infections and Pneumocystis pneumonia

Front 240

SCID

Back 240

group of disorders with leukopenia, impaired CMI, low/absent Abs, underdeveloped secondary lymphoid tissues.
persistent thrush or skin rashes by 3 months old. Medical emergency- rapidly fatal if not treated with bone marrow transplant
-X-linked: mutations in cytokine receptor subunit gamma c, blocking multiple cytokine pathways impt. in lymphocyte dev
-Adenosine deaminase def: intracellular accum of deoxyadenosine in lymphocytes, which converts to dATP and inhibits ribonucleotide reductase, halting DNA synth. Reduced numbers of T and B cells, with low serum Ab

Front 241

DiGeorge syndrome

Back 241

failed dev of 3rd and 4th pharyngeal pouches: thymic aplasia/hypoplasia with low T cells, dysmorphic facies, cardiac defects (type B interrupted aortic arch, truncus arteriosus), parathyroid hormone def (hypocalcemic tetany), cognitive impairment.
-Complete: no Abs, normal B cell #
-Partial: Abs normal, normal B cell #

Front 242

Wiskott-Aldrich syndrome

Back 242

X-linked recessive defect in a cytoplasmic actin regulator protein specific to hematopoietic cells.
thrombocytopenia, eczema and opportunistic infections. Progressive secondary depletion of T cells.
Normal IgG, high IgA and IgE and low IgM.
If it occurs in 1st decade, it will require bone marrow transplantation

Front 243

X-linked lymphoproliferative dz

Back 243

absence of SAP protein. SAP = SLAM-associated protein, SLAM = signaling lymphocyte activation molecule.
results in profound inability to combat EBV!! because normal T-B cell interaction is impaired, leading to unregulated growth of EBV-infected B cells

Front 244

Ataxia- telectangtasia

Back 244

autosomal recessive defect in DNA repair mechanisms causing neuronal degen in cerebellum
Ataxic-dyskinetic syndrome begins in early childhood, followed by telangiectasias in conjunctiva and skin.
70% are also immune def (both cellular and humoral) and have increased susceptibility to bacterial and viral infections of lung and sinuses.

Front 245

MHC Class II deficiency

Back 245

uniformly fatal in 1st or 2nd decade of life if not treated with bone marrow transplantation

Front 246

Phagocytic cell deficiencies in general

Back 246

increased susceptibility to normal, nonpathogenic bacteria and fungi
usually a mutation that affects the innate immune system

Front 247

Chediak-Higashi syndrome

Back 247

auto recessive defect in LYST gene (still being characterized)
sx: recurrent infections, partial albinism, multiple neuro abnormalities. many die in childhood.
Neutrophils are fewer, have impaired chemotaxis and intracellular killing, and abnormal giant cytoplasmic granules (fusion of lysosomes and endosomes).
impaired NK cell function

Front 248

Congenital Neutropenias

Back 248

absolute neutrophil count <500 cells/microliter (though these few cells are functioning normally)
(significant risk of bacterial and fungal infections!)
if persistent = Kostmann's syndrome
can also be cyclic (regular 21 day cycles)

Front 249

Leukocyte Adhesion Deficiency

Back 249

defect of integrin or selectin, which mediate leukocyte adhesion to endothelium.
recurrent, often necrotizing infections of skin, upper & lower airways, bowel

Front 250

Myeloperoxidase (MPO) Deficiency

Back 250

most common neutrophil disorder! tho most cases are clinically silent.
caused by def of MPO (heme binding protein that makes pus green, and catalyzes conversion of hydrogen peroxide to hypochlorous acid- bleach)

Front 251

Defects in the interferon-gamma function in mononuclear cells (i.e. phagocytes and lymphocytes)

Back 251

assoc. with failure to form granulomas, recurrent disseminated non-tuberculous mycobacterial and Salmonella infections

Front 252

Complement Deficiencies in general

Back 252

recurrent systemic bacterial infections (ex. meningitis)

Front 253

Deficiencies in early complement components (C1, C2, C4) and alternative pathway (factors I and H, properdin, C3) associated with

Back 253

pneumonia, and higher rates of collagen vascular dz (CVD) such as lupus

Front 254

Deficiencies in terminal complement components (C5-C9) associated with

Back 254

pathogenic Neisseria infections

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Chronic Granulomatous Dz

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genetically heterogeneous group of disorders of phagocytic cell oxidative metabolism (NADPH oxidase), allowing recurrent life-threatening infections of the lung, skin, and bone with bacteria and fungi.

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Which species cause most CGD infections?

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S. aureus, Bacillus cepacia, Serratia marcescens, Nocardia, Aspergillus.

USE ABX PROPHYLLAXIS!

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Most common form of CGD

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X-linked mutation in transmembrane component of cytochrome b588

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Describe NADPH oxidase

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5 subunits (2 form heavy and light chains of cytochrome b588, 3 form cytosolic complex)
When phagocyte activated, cytosolic complex associates with b588 complex and uses NADPH as a cofactor to generate superoxide from oxygen

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NBT test

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nitroblue tetrazolium test
simple and rapid determination of phagocyte NADPH oxidase activity
dark blue/black precipitate in cells = normal
absence = CGD

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Signs of congenital infections in infants

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low birthweight, microcephaly, purpura, jaundice, seizures, chorioretinitis, cataracts, hepatosplenomegaly, deafness, chronic rash

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Classic causes of congenital infections

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ToRCHeS
Toxoplasmosis
Rubella
CMV
Herpes
Syphilis

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Other (non-ToRCHeS) causes of congenital infections

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VZV (rare but severe), Lymphocytic Choriomeningitis Virus, Parvovirus B19 (hydrops fetalis and fetal wastage), HIV

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Causes of spontaneous abortion

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influenza, measles, mumps, enteroviruses, Listeria monocytogenes

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Causes of neonatal infections

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Neisseria gonorrhoeae, Chlamydia, HSV, Group B Strep, E. coli, Listeria

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Which dzs can you screen for in pregnant women?

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Screen early for Ab to rubella, syphilis and Hep. B.
HIV testing and serological tests for HSV, CMV, etc.

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Rubella's effects on Pregnancy

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Teratogenic for first-time infection in first trimester, less so in second trimester.
may cause abortion, stillbirth, complications, congenital infection, or normal baby
Sx: cataracts, pulmonary arterial hypoplasia, patent ductus arteriosus, hearing loss, intrauterine growth retardation, hsm, malformations.
After birth, may cause hearing loss after months or years
tx: prevent with VACCINATIONS

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Syphilis' effects on Pregnancy

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worst in first 4-6 months, but can occur at any time.
Can cause miscarriage, stillbirth and intrauterine growth retardation.
Early sx: osteochondritis, rhinitis "snuggles," rash (incl. palms and soles), hsm and lymphadenopathy
Late sx: Hutchinson's triad (teeth, interstitial keratitis, 8th nerve deafness), Clutton's joints (painless hydrarthrosis), Saddle nose, neuro (mental retardation, convulsive disorder, blindness, deafness, juvenile general paresis)
tx: PCN (during preg or at birth)

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Hutchinson's triad

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Hutchinson's teeth (notches on biting surfaces), interstitial keratis (corneal inflammation), 8th nerve deafness

late manifestation of congenital syphilis infection

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Clutton's joints

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painless hydrarthrosis (watery fluid in cavity of a join, esp. knees)

late manifestation of congenital syphilis infection

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saddle nose

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maxilla does not grow fully, resulting in concave configuration in the middle section of the face and a protruding mandible.
potentially perforated nasal septum from inflammation of the nasal mucosa (depression on roof of nose)

late manifestation of congenital syphilis infection

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Toxoplasmosis in pregnancy

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obtained from ingesting oocysts in cat feces or tachyzoites in undercooked meat.
Worst period: first 4 months, only primary infections cause problems, and they only happen to 40%
Sx (if at birth, sequelae severe!!): chorioretinitis, diffuse intracranial calcifications, hydrocephaly, hsm, anemia, seizures.
If asx at birth, 50-80% go on to have chorioretinitis.
tx: pyrimethamine and sulfadiazine for 1 year

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What is the most common congenital infection?

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CMV

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CMV' effects in pregnancy

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primary infection (or infection with different strain) will cause 1/3 to be infected, of which 10-15% have sx, and another 5-10% are asx but have sequelae (hearing deficits, chorioretinitis, mental retardation).
can also be transmitted via breast milk, but this won't lead to hearing defects or mental retardation.
Sx: CMV Inclusion dz- very poor prognosis if all sx are present: petechial rash- blueberry muffin, periventricular calcifications, chorioretinitis, microcephaly, hsm, jaundice)
tx: ganciclovir may be indicated

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passive immunization

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give Abs against an organism
ex. maternal Ab, IV or IM immune globulin, specific immunoglobulin, antitoxins, RhoGAM for Rh- moms with chance of Rh+ child

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What are immunoglobulins and what are common uses?

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contain Ab extracted with cold EtOH fractionation
-admin on regular basis to some immunodeficient persons
-passive immunity against Hep. A, measles, etc
-prophy for travelers to Hep. A endemic regions w/o vaccine
-specific immunoglobulins can be obtained from plasma with high titer to specific Ag like Hep B, or rabies. Won't prevent infection but can reduce dz severity

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Active immunization

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Abs against an organism are raised by host immune system following vaccine adming

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characteristics of organisms that we may be able to eradicate by vaccination (ex. smallpox)

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no animal reservoir
one serotype
infections are symptomatic (easily ID)
vaccine is stable/transportable
vaccine provides long lasting immunity
helps if virus is "hit and run," but possible if not (ex. VZV)

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Inactivated Vaccine Pros

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little/no risk of infection
low risk of contamination
stable at room temp

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Inactivated Vaccine Cons

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may not stimulate local immunity
stimulate poor CTL response
neutralizing Ab might not be as efficient
protection is relatively short term and may require boosters

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Examples of inactivated vaccines

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Toxoids: Diptheria and tetanus
Subunit/component vaccines: H. flu, S. pneumo, N. meningitidis, Hep. B
Killed organisms: Salk polio, influenza, rabies, plague, pertussis, cholera

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Live attenuated Vaccine Pros

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active in all phases of immune response
raise local (mucosal) immunity
immunity is durable and efficient
production cost is lower

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Live attenuated vaccine cons

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higher potential for contaminating organism
potential to cause dz (ex. Sabin)
could revert to virulent organism
feared that they might lead to congenital infection (esp. rubella, measles)
need special storage conditions to be kept alive

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Examples of live attenuated vaccines

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bacteria: BCG- used to vaccinate against TB, new typhoid
virus: measles, mumps, rubella, Sabin polio and VZV

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HSV effects on pregnancy

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primary (>50% chance of transmission) or recurrent (5% chance of transmission) infection of mother, if active at birth, can cause severe complications. Passed to baby AT BIRTH
Sx: life-threatening condition in 1st month of life. vesicles (range from mild to severe), conjunctivitis, keratitis, chorioretinitis (--> vision loss), disseminated dz (jaundice, encephalitis, DIC, pneumonia, sepsis with seizures) -->90% mortality
tx: culture active lesions during pregnancy, C-section if active dz. Acyclovir

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VZV effects on pregnancy

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congenital/transplacental infection is very rare (<1%) and very severe.
Sx: scars, hypoplastic limbs, small, high mortality

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HIV effects on pregnancy

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25% transplacental infection, plus a higher rate of miscarriage for HIV+ mothers
dx of HIV in newborn: often + to ELISA and Western blot b/c of maternal Abs, must be confirmed by: DNA PCR (standard of care), RNA PCR (2nd choice), Viral culture (less sensitive), p24 Ag (only 18% sensitive at birth)

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Interventions to prevent vertical transmission of HIV

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Baseline: 25% transmission w/o intervention
Combo antiretroviral tx for mother that decreases viral load to <400, with AZT given IV at delivery and PO to baby for 6 weeks: <2% transmission.
Nevirapine 1 dose during labor, another within 72 hours of birth decreases transmission by 50%
AZT during pregnancy and labor and to infant for 6 weeks: 8% transmission

Note: If viral load <1,000, C-section gives no advantage.
Mother's plasma viral load is most predictive of transmission

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CDC Categories of Bioterrorism agents

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A: easy person-to-person transmission, high mortality rates, major public health impact (panic, require special action for preparedness).
B: moderately easy dissemination, moderate morbidity, low mortality, difficult to detect.
C: COULD be engineered for mass dissemination b/c readily available, easy to produce and disseminated, potential for high morbidity, mortality and public health impact

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"Signs of bioterrorism"

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multiple simultaneous patients with similar clinical syndromes
severe illness among the healthy
predominantly resp. symptoms
unusual (nonendemic) organisms
unusual abx resistance patterns
atypical presentation
unusual patterns of dz (geographic co-location of victims)
intelligence info
reports of sick/dead animals or plants

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Bacillus anthracis histo

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Gram + rod, aerobic, spore-forming, non motile, grows on blood agar plates

dx by serology

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Where are B. anthracis toxins encoded?

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2 plasmids - pXO2 for capsule, pXO1 for the 3 exotoxins

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Dz caused by Bacillus anthracis

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Cutaneous anthrax (common), Inhalation anthrax (lethal), GI anthrax

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What are the exotoxins of Anthrax?

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EF (Edema factor), LF (Lethal factor), PA (Protective Ag)

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EF function

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B. anthracis exotoxin, calmodulin-dependent adenylate cyclase. also impairs phagocytic activity

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LF function

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B. anthracis exotoxin, zinc metalloprotease, cleaves MAP kinases 1 and 2, CELL DEATH for macrophages

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PA function

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B. anthracis exotoxin, protein subunit that faciliates entry of EF and LF into cells
(Furin cleaves/releases PA20, PA63 forms heptamer, toxin enzymes bind to PA63, ENDOCYTOSIS, acidification causes PA63 to insert into membrane and translocate toxic enzymes to cytosol)

named b/c a component in vaccine

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Anthrax Vaccine Absorbed (AVA) schedule

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3 subq at 0, 2, 4 weeks, 3 booster at 6, 12, 18 months, Annual booster

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Why Anthrax is a good bioterrorism agent

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very stable
relatively easy to weaponize
inexpensive to produce in large quantities
Inhalation is highly fatal

-developed as biological weapon by Japan, US and UK in 1930s-40s
-notorious for intentional mail contamination in Sept/Oct 2001

But note: no person-to-person transmission!

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Cutaneous anthrax

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95% of anthrax infections (common!)
"woolsorter's dz"- obtained usually from occupation exposure of cuts/abrasion by organism or spores (in wool, hides/leather, insect bites).
itchy bump develops into vesicle in 2-3 days, then painless black eschar in 7-10 days.
untreated, 20% fatal

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Inhalation anthrax

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infectious dose = 8,000 to 15,000 spores
incubates 1-6 days, then nonspecific sx (fever, nonproductive cough, fatigue, malaise, myalgia).
1-3 day improvement, then sudden fever and respiratory distress followed by shock and death in 24-36 hours. usually fatal

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GI anthrax

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usually in poor, developing countries with food shortages or inadequate vet inspection (SubSaharan Africa, Central Asia, Russia, India, Thailand)
follows consumption of contaminated meat (rare, tends to occur in family clusters, often concurrent cutaneous cases from butcher or chef). 1 in 64 infected animals causes dz
Sx: n/v, fever, ab pain, vomiting blood and severe diarrhea
untx, 25-60% mortality

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Anthrax tx

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IV doxycycline or quinolones for 4 weeks, plus vaccination.
Children get doxycycline or PCN

Prophy: doxycycline or cipro for 8 weeks plus vaccination.

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Decontamination of Anthrax spores

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- Autoclaving with 15-20 lbs steam at 121 degrees Celsius for 15-20 minutes kills all spores
- Fumigation with formaldehyde for >4 hours or immersion in formaldehyde for >12 hours, with full penetration, also kills all spores
-Gamma radiation works on goat hair and mail
-Incinerate contaminated animal carcasses (burying may lead to new livestock cases or infection of digging scavengers

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Which species have we learned about that is a Spirochete?

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Leptospira

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What are Spirochetes?

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Gram negative, long coiled cell bacteria

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Can Leptospira be cultured?

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Yes, but it grows very slowly.

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How many distinct antigenic types of Leptospira are there?

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250

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Leptospirosis dx

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serology, culture or PCR of body fluids

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Course of leptospirosis

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biphasic
Phase 1: HA, muscle aches, vomiting or diarrhea
Phase 2: Weil's dz (kidney/liver failure or meningitis)

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How long does Leptospirosis last?

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a few days to 3 weeks+

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How long is Leptospira's incubation period?

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2 days to 4 weeks

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How can humans prevent leptospirosis?

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avoid contaminated surface water,
vaccinate domestic animals

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leptospirosis sx

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can be asx, tends to be variable.
high fever, HA, chills, muscle aches, vomiting, uveitis, ab pain, diarrhea, rash, jaundice

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What may occur if Leptospirosis goes untreated?

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Weil's dz: kidney damage, meningitis, liver failure or respiratory distress (rarely death)

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leptospirosis tx

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often self-limited and requires no ABX, but treating in order to shorten the illness and decrease shedding in urine is a good idea.
Doxycycline, ceftriaxone or penicillin

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How is leptospirosis acquired?

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exposure to urine of infected animals (through swallowing or touching contaminated water or soil)

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What animals can transmit Leptospirosis?

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cattle, pigs, horses, dogs, rodents, etc.

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Do animals show signs of leptospirosis?

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range from no symptoms to overt illness

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Listeria monocytogenes: histo, mechanism of dz

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small Gram + rod, intracellular (internalin A and B promote cell invasion, hemolysin/listeriolysin O releases organism from phagosome, intracellular growth occurs in cytosol).
Acquired from ingestion of contaminated dairy, uncooked meats, soft cheeses, or vegetables grown in contaminated soil. (Pasteurize your milk and cook your food!)
Bacterial protein ActA catalyzes actin polymerization to spread from cell to cell

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Listeria monocytogenes dz and tx

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Bacteremia and meningitis in immunosuppressed -esp. CMI impaired (chemo, pregnant, neonates, transplant, alcoholics)
In preg women: mild illness with fever, myalgias, malaise, backache. can spread transplacentally causing chorioamnionitis, premature labor and intrauterine fetal demise
tx: ampicillin and gentamicin

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Brucella spp.: histo, mechanism of dz

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Gram - coccobacilli, facultative intracellular. LPS is smooth or rough.
Acquired from ingestion of contaminated milk/dairy, handling infected animals with abraded skin, or laboratory aerosol inhalation (use biosafety level 3 precautions).
Cases in CA, FL, TX, VA. Nationally reportable!

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What CDC Category is Brucella and why?

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B, stable with only 10-100 req'd for infection.
no person-to-person transmission and mortality <5%

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Brucella species by host

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B. abortus: cattle, bison, elk
B. melitensis: goats
B. ovis: sheep
B. suis: pigs, reindeer
B. canis: dogs (rare)

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Brucella dz (Brucellosis)

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Extremely variable presentation.
Incubation 5 days to >6 months
Acute (<8 weeks): nonspecific "flu-like" (fever, sweats, malaise, anorexia, HA, myalgia, back pain)
Undulant (<1 year): undulant fevers, arthritis, epididymitis, orchitis, neuro in 5%
Chronic (>1 year): chronic fatigue, depression, arthritis, variable sequelae

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Yersinia pestis histo, epi and mech of dz

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Gram - "safety pin," bipolar staining bacillus (Fam Enterobacteriaceae), nonmotile, lactose -, requires plasmid for virulence
worldwide distrib in rodent fleas, mainly SW US in rat (urban) or squirrels, prairie dogs (sylvatic) - control rodents near people!

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What CDC Category is Yersinia pestis and why?

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A, widespread in environment, easily cultured, a aerosol/pneumonic plague would require intelligence and tech, but could spread person to person

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Yersinia pestis dz

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Bubonic plague: most common, buboes (swollen lymph nodes), fever, chills, HA, extreme exhaustion.
Pneumonic plague: severe resp. illness with high fever, chills, cough, breathing difficulties, rapid shock and death. person-to-person transmission
Septicemic plague: fever, chills, prostration, ab pain, shock, bleeding into skin and other organs.
Untx, 5-90% die. Tx, 15% mortality.
Prophy for exposure, vaccine only given to scientists and wild animal handlers

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Francisella tularensis histo, mech of dz

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Gram - bipolar staining coccobacillus (pleomorphic). requires rich media with cysteine
Acquired by tick bite, contact of unbroken skin with infected cottontail rabbit tissue/fluid/pelts, laboratory exposure or inhalation (?)
Midwest summer (ticks common), East of Mississippi in winter (rabbit hunting season)
ONLY 10-15 organisms req'd for tularemia!

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What CDC Category is Francisella tularensis and why?

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A, only 10-15 organisms req'd to cause dz, widespread in environment, easily cultured (enriched media with cysteine), though airborne packaging requires advanced intelligence and tech

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Francisella tularensis dz

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Tularemia! Incubation 1-21 days, presentation depends on site of entry
Ulceroglandular tularemia (80% of cases, entry through skin): papule becomes ulcer with fever and lymphadenopathy. Bacteremia develops with organisms trapped in RES forming granulomas. can survive in macs and monocytes, dz lasts 1 month and 5% mortality w/o tx
Pneumonic tularemia: most serious form, necrotizing granulomata cause bronchopneumonia, bronchitis, tracheitis. Bacteremia when macs enter lymphatics. 30% mortality untx
Typhoidal tularemia: endotoxemia with continuous fever, severe HA, mylagias and hsm

Tx: ABX (see Sanford). wear protective clothing and get vaccinated. Infection gives partial immunity

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Borrelia histo

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Gram - spiral organisms, visualized with darkfield, phase contrast, Wright/Giemsa stains, Dieterle's/Warthin-Starry silver stains, or IF w/ Ab.
motile (flagella), no toxins, but do have outer membrane lipoproteins that are B cell mitogens and induce proinflamm. cytokines
1 linear maxi chromosomes, other linear mini chromosomes and supercoiled circular plasmids
Microaerophilic, fermentative, complex nutritional requirements but can be cultured, tho slow growing. Attach to cells via carbohydrate receptors. Cross react with other Spirochetes

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Borrelia recurrentis dz

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causes epidemic louse borne relapsing fever (LBRF), transmitted by the crushing of Pediculus humanus var corporis (which lives for a few weeks, feeding frequently). Hemolymph of human body louse is infected, not saliva nor feces.
Occurs particularly in developing world, esp. war, famine and wherever there are congregations of refugees.

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Borrelia hermsii dz

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causes endemic tick-borne relapsing fever (TBRF), transmitted by bites of Ornithodoros soft-bodied ticks in warm, humid environments at altitudes between 1500-6000ft (esp. NW and SW US). Found in caves, decaying woodpiles, rustic dwellings.
Reservoirs are vertebrates: rodents (red squirrels) or wild/domestic pigs and bats.
Ornithodoros ticks are fast feeders (only bite for 15-20 minutes), bite at night and can survive for years without a blood meal.

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Relapsing fever presentation and tx

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single spirochete can initiate infection, after that, approx. 1 week cycles of fever, potentially also HA, arthralgia, myalgia, rigors, photophobia, cough, hsm, jaundice, neuro symptoms (more common with LBRF).
Fatality rates vary between LBRF and TBRF. LBRF untx: 10-70%, 2-5% treated. TBRF untx: 4-10%, <2% treated, but tend to have higher fevers (>102) and more and longer relapses (requires longer treatment!)
Tx: tetracycline or erythromycin. Anticipate Jarisch-Herxheimer reaction in 80% LBRF patients

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How do Borrelia recurrentis and hermsii cause RELAPSING fever?

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During afebrile periods, spirochetes are sequestered in internal organs, undergoing antigenic variation of Vmp protein (of which it has 30-40 serologies on a linear plasmid), so as the IgM clears one serotype, the next comes to predominate and cause a relapse.
It's likely that something more than IgM is at work, because fewer than 30-40 cycles are observed.

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Borrelia hermsii and recurrentis dx

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demo organism in peripheral blood (tho it can be culture, labs are rarely equipped to do so), and a PCR test is being developed

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Jarisch-Herxheimer reaction

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reaction in 80% LBRF patients to antibiotic treatment (tetracycline and erythromycin for relapsing fever)
-severe rigors, leukopenia, increase in temp and decrease in BP

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Borrelia burgdorferi sensu lato complex

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causes Lyme dz (multisystem inflammatory dz).
most common arthropod vector borne pathogen in North America (esp. among children and middle aged adults, between May and October)
3 groups of organisms:
Group1: Borrelia burgdorferi sensu stricto - all US cases, and in Europe
Group2: Borrelia garinii - Asia and Europe
Group3: Borrelia afzelii - Asia and Europe

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Borrelia burgdorferi sensu stricto

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One linear maxi chromosome with several linear and coiled virulence plasmids (lose plasmids, no longer virulent). relies on host for most nutritional requirements.
Outer membrane proteins (plasmid encoded) are OspA, OspB, OspC. Different ones occur in ticks vs. humans. Also has flagellin and heat shock proteins (crossreactive with other species!)
-can bind human plasminogen and urokinase-type plasminogen activator, GAGs and many integrins.
-induces production of inflammatory cytokines incl. TNFalpha and gamma IFN

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Vectors and Reservoirs of Lyme Dz in US

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All ticks hang on undersides of shrubs/grass, latch on to warm CO2-producers walking by and find place to bite and transmit Borrelia in 48-72 hours (only 1-2% of infected ticks transmit Borrelia)
East Coast/Midwest: Ixodes dammini/scapularis: 10-50% infected, preferred host for larval/nymphal stages (white-footed mouse) is an asx reservoir. 90% of transmission is in nymph form, adult tick feeds on white-tailed deer.
West Coast: Ixodes pacificus: 1-3% infected, lizard host of nymph and larval stages is not infected, reservoir is dusky-footed woodrat (which is usually parasitized by Ixodes neotomae instead of pacificus!).

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First stage of Lyme dz

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Early Localized Dz, 30-30 days post infection.
Erythema chronicum migrans (found near axilla, inguinal area, behind knee, belt line. expands over few days into bull's eye pattern, forms satellites in 10%. Generally asx, though it may itch or burn, or be accompanied by viral syndrome (HA, myalgia, arthralgia, malaise, lymphadenopathy)).

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Second stage of Lyme dz

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Early Disseminated Dz: weeks-months post infection
Symptoms wax, wane and may change organ systems, or may even be first manifestation if first stage was skipped.
Sx: MSK (myalgia, arthralgia, arthritis), Cardiac (8% develop transient heart involvement- usually AV heart block or myopericarditis), Neuro (10% - lymphocytic meningitis, cranial nerve palsies, radiculoneuritis)

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Third stage of Lyme dz

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Late Disseminated Dz (months -years post infection, may not have been preceded with other sx)
Sx: MSK (80% - arthralgias, intermittent arthritis, chronic monoarthritis, assoc. with HLA-DRB1*0401)
Neuro (encephalopathy, cognitive dysfcn, peripheral neuropathy)
Cutaneous: Acrodermatitis chronica atrophicans (ACA) - scleroderma-like lesions. Not seen in US, only Europe.

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Dx of Lyme dz

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patient hx and clinical findings are crucial, only use ELISA + Western blot to confirm.
Late dz: organisms are absent from blood, so a PCR test for tissue is development

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Tx of Lyme dz

Back 345

depends on symptoms.
Early dz or arthritis: Doxycycline or amoxicillin (or Cefuroxime if they can't take either)
Neuro sx, heart block: Cetriaxone

Prevention with clothes and DEET, prophylaxis is not indicated

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Urethritis sx, likely causes and differentiation for tx

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sx: urethral discharge, dysuria, distal urethral itching
Gonococcal (GU) or Nongonococcal (NGU)- usually Chlamydia though may be Ureaplasma urealyticum, Mycoplasma gentalium, HSV, Trichomonas.
Dx GU by Gram stain, culture, DNA probes or NAATs but also search for Chlamydia coinfection by Ag capture EIA, IF, or NAATs.
Tx: Gonorrhea: Cefixime, Ceftriaxone or quinolones (unless in Asia, Pacific Islands or CA)
Chlamydia: Azithromycin or doxycycline

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Epididymitis likely causes

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<35 yo - Chlamydia or Neisseria gonorrhoeae
>35 yo - facultative Gram - rods

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NAATs

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Nucleic acid amplification tests.
cost more but are more sensitive than culture for detection of GU. May be tested on urine rather than urethral swab!

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Vulvovaginitis sx, likely causes

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Abnormal vaginal discharge.
Scant, cheesy discharge = Candida
Yellow, frothy, pH>5 = Trichomonal vaginitis
Malodorous, white-gray, pH>5 = Bacterial Vaginosis (anaerobes like Gardnerella vaginalis or Mobiluncus curtisii)

Candidiasis and Trichomonal vaginitis also have vulvar itching, dysuria, vulvar erythema or edema. Candidiasis has adherent plaques.

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Histo of vulvovaginitis causes

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Candidiasis: epithelial cells, leukocytes, budding yeast, pseudohyphae
Trichomonal vaginitis: leukocytes and mobile flagellate trichomonads 50-70% of the time. 20% fishy odor with KOH
Bacterial vaginosis: Clue cells (epithelial cell covered in bacteria), few leukocytes, mixed flora outnumbering lactobacilli. 40% fishy odor with KOH

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Treatment and implications of vulvovaginitis

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Depends on causative organism
Candidiasis: Topical or oral imidazole (miconazole or clotrimazole topically, fluconazole orally)
Trichomonal vaginitis or Bacterial Vaginosis: metronidazole.
Note: in Trichomonal vaginitis, partner should also be treated.

Candidiasis rarely sexually transmitted, may follow ABX use. Recurrent candidiasis might signify HIV.
Trichomonal vaginitis often accompanies GC cervicitis, and may predispose to HIV transmission

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Mucopurulent cervicitis

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infection of the columnar epithelium or subepithelium of the cervix by chlamydia or gonococci. usually women don't have sx or just don't seek treatment.
organisms ascend the genital tract to produce PID

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Risk factors for PID

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hx of bacterial STD or PID, high number of sexual partners, douching.

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PID dz

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difficult to make, often asx, and the sx (dull, aching abdominal pain) have a wide differential. But, since sequelae are severe (infertility, ectopic pregnancy and chronic pelvic pain), treat all patients that are suspected of having PID.

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Fitz-Hugh Curtis syndrome

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perihepatitis, associated with PID (usually Chlamydia more so than Gonorrhea).
sx: RUQ pain and tenderness

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What is the most common agent of sexually transmitted genital infections in the USA?

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Chlamydia trachomatis
(highest rates among adolescent women)
- cervical infection is most common syndrome, but >50% are asx (if sx, mucopurulent cervical discharge, cervical friability and cervical edema. assoc. w/ urethral infection, and 30% go on to PID)

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Gold standard of gonorrheal dx

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culture on Thayer Martin media.
Note: only 60% of Gram stains in women with symptoms are positive!

Women often have asx infections but 90% of infected men have sx!

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Genital Ulcer Dz (GUD) most likely causes

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increase the risk of HIV transmission and HIV acquisition.
Most common causes:
-Herpes
Syphilis (Treponema pallidum), Lymphogranuloma Venereum (LGV), Haemophilus ducreyi

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Det. causative organism based on ulcers in GUD

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One painless, indurated lesion with clean base, heals spontaneously: syphilis.
Multiple painful, irregural, purulent uclers: Chancroid.
Multiple small painful grouped vesicles coalesce to form shallow ucler: Herpes.
Painless ulcers, with painful nodes in matted clusters uni-or bi-laterally = LGV (more often males than females, rectal dz in recipients of anal sex)

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Tests to run on GUD

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Darkfield microscopy, RPR/VDRL, FTA, MHA-TP: syphilis
Culture of ulcer base, NAAT: Chancroid
Tzanck smear, DFA, culture, serology: Herpes
Serology (CF, microIF Ab): LGV

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Tx for GUD causes

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Syphilis: PCN
Chancroid: Azithromycin or Ceftriaxone
HSV: Acyclovir
LGV: Doxycycline

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Bunyaviridae
+/- ss/ds RNA/DNA
icosahedral/helical
enveloped/naked

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3 segmented - ssRNA in a circle (L, M, S)
3 helical nucelocapsids
enveloped

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Which virus uses ambisense txn?

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Phlebovirus (a genera in Bunyavirus family)

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Rift Valley Fever Virus

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caused by Bunyavirus
vectors: Culex and Aedes mosquitoes, aerosol from infected animals. Bite and kills a lot of cows, esp. with heavy rainfall.
Human Dz: short incubation (2-7 days), then 7-8 days of sx: fever, HA, retro-orbital pain, photophobia, myalgias, potentially with encephalitis, retinitis, and hemorrhagic fever.
<1% mortality (15% in hospitalized patients)
Dx: ELISA for IgM Ab
Tx: supportive care and Ribavarin if early enough. Vaccine has protective Ab against N, G1, G2

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Which 4 Bunyaviridae genera infect humans

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Bunyavirus (Rift Valley Virus)
Hantavirus (Sin Nombre Virus) - not spread by arthropods (by mammals/rodents' urine/feces instead), all others are arthropod borne
Phlebovirus (uses ambisense replication)
Nairovirus

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Bunyaviridae Life Cycle

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FAST (6 hours)
Receptor mediated endocytosis followed by pH mediated fusion (beta3 integrin is Hantavirus' receptor).
Transcriptase (encoded on L) transcribes subgenomic mRNA in capsids and sticks on caps.
Translation occurs w/o splicing or polyadenylation.
Rep in cytoplasm on signal from N protein (encoded on S) binding to viral RNA, preventing cap formation.
M segment codes for G1 and G2, which undergo cotranslational cleavage in rough ER, stuck into membrane and glycosylated. May also transcribe nonstructural proteins NSs and/or NSm.
Bud from smooth ER into associated intracytoplasmic vesicles. Disrupts protein synth and membrane, killing the cell

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Tx Bunyaviridae

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Interferon
(virus clearance correlates with host IFN production)
MxA, a GTPase, is induced by IFN and inhibits Bunyavirus rep

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Ribavarin

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tx for Rift Valley Fever and Lassa Fever (NOT Sin Nombre)
resembles inosine monophosphate, incorporated into genome during replication, causing multiple reading errors

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Sin Nombre Virus

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Bunyaviridae family
vector: white-footed deer mouse (expanded pop after rainy years). Aerosolized rodent excrement transmits dz.
HPS: Hantavirus Pulmonary Syndrome. Sx: fever, myalgia, vomiting, fatigue, cough, HA, rapid hypoTN, low cardiac index and increased SVR, bilat. diffuse infiltrates, thrombocytopenia, hypocapnia and hemoconcentration.
Elevated WBC with bands, low platelets and elevated LDH.
Tx: supportive care. Abs seem to be raised but not sure if that actually fights off virus
Mortality = 50%, better if recognized early and hospitalized. Minimal sequelae if survived

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Pathology of HPS

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Edema with proteinaceous fluid in alveolar spaces, virus stays in the vascular endothel.

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Dz caused by Arena virus

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Lassa Fever
Lymphocytic Choriomeningitis
Hemorrhagic Fevers

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How are arenaviruses transmitted?

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inhalation of aerosolized rodent excrement (urine and fevers) or contact via skin abrasions.
Each one has it's own rodent species, in which it causes persistent infections

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Arenavirus genome

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frequently polypoid, 2 helical nucleocapsids, 2 ambisense ssRNA segments that can circularize and reassort.
L- codes for transcriptase (L protein) and zinc finger regulatory protein (Z protein)
S - codes for nucleocapsid (NP) and envelope glycoprotein precursor (GPC)

replicates in cytoplasm but does not generally kill the cell

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Arenavirus Life cycle

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slower, produces high viral titer
Entry into activated monocytes via alpha-dystroglycan and pH mediated fusion/direct PM fusion.
In cytoplasm, makes nucleoprotein and transcriptase, stealing cellular RNA caps. Makes glycoproteins and bud off from plasma membrane.
NOT SENSITIVE TO IFN

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Lassa Fever

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caused by Arenavirus, endemic to Central and West Africa
Transmitted (esp. January to April): multi-mammate mouse to humans via aerolization, food contamination, eating mouse. OR human to human via direct tissue contact, needlestick, or inhaled virus.
Incubation 5-21 days
Sx: not as bad if acquired early in life or native: fever, HA, malaise, pharyngitis, retrosternal pain, cough, GI sx, some patients have bleeding, neck/face swelling and shock. DEAFNESS afterwards
Mortality = 2%, illness lasts 1-4 weeks
Dx: CF Ab (serology often negative at presentation)
Tx: supportive care, Ribavarin (tho this doesn't prevent deafness). Immunization not protective

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signs of poor prognosis for Lassa Fever

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high viremia, AST>150, bleeding, encephalitis, edema, 3rd trimester of pregnancy