LOs: 21-24 Flashcards
21 Causes of FUO:
Infections:
Blood cultures
- Endocarditis (1 cause)
- AIDS (1 cause)
- Endemic areas (1 infection, 1 cause)
Imaging studies
- Chest radiograph / CT (3)
- Abdomen CT (2)
Biopsies
- Lymph node (5)
- Liver (2)
Bone marrow biopsy & culture
- Neoplastic disorders (3)
- Intracellular infections (1)
Elderly (3)
- Bartonella
- Mycobacteria
- TB, Histoplasma capsulatum
- Lymphoma, histoplasmosis, sarcoidosis
- Intra-abdominal abscesses, lymphoproliferative disorders
- Lymphoma, toxoplasmosis, Kikuchi’s disease, TB, sarcoidosis
- Granulomatous hepatitis, TB
- Lymphoma, leukemia, multiple myeloma
- Disseminated histoplasmosis
- TB
- Endocarditis
- Intraabdominal abscess
21 Treatments for FUO:
Not ___
Except
- Culture-negative endocarditis
- Presuemd temporal arteritis
- Suspected military TB in elder pts & in pts w/ AIDS; pts w/ connective tissue diseases taking corticosteroids, methotrexate, or infliximab; recipients of solid organ transplants
Empiric (antiTB drugs, antibiotics, steroids)
- Antibiotics
- Corticosteroids
- AntiTB
21 H&P for FUO:
Infections:
Medical/Surgical History
- Previously treated chronic infections (2)
- Transfusions (3)
Medications (___)
- Drug therapy (4 drugs)
Social History
- Recreational drugs (2)
- Sexual activity (HIV)
- Animal/insect exposure (5)
- Dietary habits (2)
- Recreational activities (3)
- Travel history (2)
Physical Exam
- Eyes (2)
- Oropharynx (1)
- Temporal artery (1)
- Thyroid gland (1)
- Lymphatic system (1)
- Genital area (1)
- Joints (1)
- Pulses in extremities (1)
- Skin rash (2)
- TB, endocarditis
- Hepatitis C, CMV, West Nile Virus
Drug therapy
- Antimicrobials
- Steroids
- NSAIDs
- Antipyretics
- Infective endocarditis, osteomyelitis
- HIV
- Salmonellosis, brucellosis, toxoplasmosis, cat-scratch disease, Q fever
- Brucellosis, Salmonella
- Sporotrichosis, leptospirosis, histoplasmosis
- TB, malaria
- Conjunctivae, endocarditis
- Oral thrush
- Temporal arteritis
- Thyroiditis
- Endocarditis
- Syphilis
- Arthritis
- Arteritis
- Endocarditis, Rocky Mountain Spotted Fever
21 Common categorical causes of FUO & examples (4)
Classic FUO
Nosocomial FUO
- C. difficile
- Drug fever
Neutropenic FUO
- Candida
- Aspergillus
HIV-Associated FUO
- HIV
- Mycobacteria
- Toxoplasma
- CMV
- Pneumocystis
- Salmonella
- Cryptococcus
- Histoplasma
- Non-Hodgkin’s lymphoma
- Immune reconstitution inflammatory syndrome
22 Definitions:
Inhalation
Aspiration
Respiration
Breathing in exogenous flora
Breathing in endogenous flora
Exposes us to microbes with every breath
22 Respiratory Tract Defense Mechanisms:
Microbial (1)
Mechanical (3)
Innate (2)
Humoral (2)
Cellular (2)
Commensal flora prevent other pathogens from coming in
- Commensal flora
Breathing out gets rid of dangerous pathogens
- Airflow
- Mucociliary elevator
- Epiglottis
Attack pathogens once they get in
- TLRs
- Airway fluid
Attack bacteria, respond to viral infections
- sIGA
- IgG neutralizing capsule/virions
Attack bacteria, respond to viral infections
- Phagocytic (neutrophils, macrophages)
- T cells (CD4, CD8, Th17)
22 Compromise of a specific defense predisposes to specific infections:
CNS injury
- Examples (2)
- Defense
- Pathology
- Conditions (2)
T cell injury
- Examples (2)
- Defense
- Pathology
- Conditions (2)
Humoral deficiency
- Examples (2)
- Pathology
- Conditions (1)
- Traumatic brain injury, cerebral palsy
- Mechanical protection
- Muscle/nerve dysfunction prevents airway protection
- Aspiration pneumonia, abscesses
- HIV, anticancer chemotherapy
- Cellular defense
- Invasion by opportunistic pathogens
- Fungal and viral pneumonia
- Immune deficiency, elderly
- Lack antibody which opsonize encapsulated bacteria
- Bacterial pneumonia
23 Hepatitis A, B, C, D, & E:
Virus Family
Genome
Transmission
Severity
Chronic Infection & Liver Cancer (y/n)
Prophylaxis
Therapy
HDV
A: Picornavirus B: Hepadnavirus C: Flavivirus D: Defective / Unclassified E: Calcivirus
A, C, E: +RNA
B: incomplete dsDNA
D: -RNA
A, E: fecal-oral
B, C, D: parenteral
A, E: self-resolving
B: sometimes severe
C: moderate
D: severe
A, E: no
B, C, D: yes
A: HAIG, vaccine
B: HBIG, vaccine
D: HBV vaccine
C, E: none
B: Interferon, Lamivudine, Emtricitabine Tenofovir, Telbivudine Entecavir, Adefovir
C: Interferon Ribavirin Boceprevir Teleprevir Sofosbuvir
A, D, E: none
HDV is only seen as a co-infection or super-infection of HBV
23 Hepatitis B Virus (HBV):
Biological Characteristics
- Genome
- Genes
- Surface antigen
Pathogenesis (6)
Diagnosis (2)
Virulence Factors (2)
Prevention (2)
Treatment
- Acute infection
- Chronic infection
- Cirrhosis / end–stage liver disease
BC
- Circular incompletely dsDNA that uses viral reverse transcriptase (unique)
- 4 genes: surface, core, pol, X
- Surface antigen is shed w/o necessarily being attached to the virus
P
- Bloodstream infection
- Gene product form S ORF (“pre-S1”) binds hepatocyte surface
- Viral replication w/o cytopathic effect
- Excess HBsAg functions as immune decoy
- Cytotoxic T-cell responses do injure liver
- Oncogenesis: viral DNA integration into host chromosome & X ORF (transcriptional activator)
D
- Detection of circulating HBV DNA in blood by PCR
- HBV serology
- Antigens: surface, core, e
- Antibodies: anti-HBs, anti-HBc, anti-HBe
VF
- Chronic infection
- HBsAg: immune decoy
P
- Hepatitis B Vaccine: recombinant, made of HBsAg
- Lamivudine (prevents reactivation)
T
- AI: HBIG
- CI: Alpha-interferon, lamivudine, tenofovir, adefovir, entecavir, emtricitabine, telbivudine
- C/ESLD: liver transplantation
HBV Serology:
Clinical manifestations
- Acute hepatitis
- Chronic hepatitis
- Hepatocellular carcnimoa
Acute Infection (4)
Chronic Infection (3)
CM
- Acute hepatitis: asymptomatic, mild, fulminant
o RUQ pain, malaise, jaundice
o Transaminase release from hepatocytes (AST, ALT)
- Chronic hepatitis: ongoing liver damage
- Hepatocellular carcinoma: transformation of hepatocytes
AI
- DNA & antigens (Ag) (surface, core, & e) come first
- “Window period” is before detectable immune response
- Anti-HBc IgM comes before IgG (aka anti-HBc total)
- Symptoms begin w/ effective immune response
CI
- HBsAg doesn’t clear
- HBeAg, if not cleared, portends higher infectivity (more viral replication)
- Anti-HBc doesn’t confer protective immunity
HBV Serology Patterns:
(1) HBV DNA
(2) HBsAG
(3) HBeAG
(4) Anti-HBcAg
(5) Anti-HBsAg
Acute (window)
Acute (active)
Acute (resolved)
Chronic/Persistent
Vaccinated
Acute (window)
(1) HBV DNA +
(2) HBsAG +
(3) HBeAG +
(4) Anti-HBcAg -
(5) Anti-HBsAg -
Acute (active)
(1) HBV DNA +
(2) HBsAG +
(3) HBeAG +
(4) Anti-HBcAg +/-
(5) Anti-HBsAg +/-
Acute (resolved)
(1) HBV DNA -
(2) HBsAG -
(3) HBeAG -
(4) Anti-HBcAg +/-
(5) Anti-HBsAg +
Chronic/Persistent
(1) HBV DNA +
(2) HBsAG +/-
(3) HBeAG +
(4) Anti-HBcAg +/-
(5) Anti-HBsAg -
Vaccinated
(1) HBV DNA -
(2) HBsAG -
(3) HBeAG -
(4) Anti-HBcAg -
(5) Anti-HBsAg +
23 Hepatitis Delta Virus:
Biological Characteristics
- Genome
- Contains…
Clinical Disease
- Infection (2)
- Severity
Diagnosis (1)
Prevention (1)
Treatment (2)
BC
- Defective RNA virus that requires HBV for infection
- Contains RNA & delta Ag enveloped w/ HBV envelope (HBsAg)
CD
- Simultaneous infection w/ HBV or superinfection of persistent HBV-infected patients
- Clinical syndrome of HDV mroe severe than HBV alone
D
- Serology for delta Ag antibody
P
- Hepatitis B vaccine
T
- Interferon-alpha
- Liver transplantation
23 Hepatitis C Virus (HCV):
Biological Characteristics
- Genome
- Family
- Presence in blood
Clinical Disease (4)
Virulence Factors (2)
Diagnosis (2)
Treatment (4)
BC
- Enveloped +RNA virus
- Flavivirus
- Quasispecies: multiple sequence isolates present at one time for immune evasion
CD
- Chronic viral infection
- Chronic hepatitis
- Cryoglobulinemia
- Cirrhosis then hepatocellular carcinoma
VF
- High mutation rate of viral RNA polymerase
- Protease blocks immune activation
D
- Serology for anti-HCV antibodies
- RT-PCR
T
- Standard: alpha-interferon + ribavirin
- New protease inhibitors: boceprevir, teleprevir, sofosbuvir, simeprivir
- Liver transplantation
- No prophylaxis or vaccine
23 Transplant-Associated Herpesvirus Infections:
Latency
Risk of transmission
Severity
Diseases associated w/ transplantation:
- HSV-1
- HSV-2
- VZV
- CMV
- EBV
- HHV-6
- HHV-8
Life-long latency can be reactivated in immunosuppressed
Risk of transmission by donor organ transplantation to non-immune recipients
More severe disease associated with first-time infection (primary infection) compared with
reactivation (secondary infection).
- HSV-1: oral & genital lesions
- HSV-2: anogenital & oral lesions
- VZV: chicken pox & herpes zoster / shingles
- CMV: hepatitis
- EBV: mononucleosis, post-transplant lymphoproliferative disease (PTLD)
- HHV-6: rash, seizures, post-transplant encephlaitis
- HHV-8: Kaposi’s sarcoma
23 Epstein-Barr Virus (EBV):
Biologic Characteristics
- Genome
- Family
- Infects…
- Establishes…
Clinical Disease: Acute Infection (3)
Clinical Disease: Chronic Infection (2)
Pathogenesis
Diagnosis
- Acute infection
- Recent or past infection
- PTLD
Prevention & Treatment for PTLD (3)
BC
- DNA virus
- Herpesvirus
- Infects B cells or nasopharyngeal cells by CD-21(-like) receptor
- Latency & immortalized human B cells
CD: AI
- Asymptomatic or mononucleosis
- Fever, pharyngitis, lympahdenopathy, atypical lymphocytosis
- Complication: hepatitis rash (from amoxicillin or penicillin) or beta-lactam splenic rupture
CD: CI
- Burkitt’s lymphoma, nasopharyngeal carcinoma, non-Hodgkin’s or Hodgkin’s lymphomas
- Post-transplant lymphoproliferative disease (PTLD)
P
- Transmission by saliva (oral secretions)
- Replication in pharyngeal epithelium
- Spread via bloodstream to B cells (tonsils, lymph nodes)
- Latency in B cells –> mononucleosis
- During latency, EBNA-1 is produced to evade the immune recognition
- PTLD: lack of CTL recognition of EBV latent antigens allows growth of latently infected B cells
- Virus gets shed in oral secretions to reinfect new B cells to replenish reservoirs
D
- AI: monospot test for antibodies
- RoPI: detect anti-EBV antibodies (IgM)
- PTLD: qPCR, biposy
P
- No vaccine or treatment
- Decrease immunosuppressive therapy
- Acyclovir & ganciclovir
- CTL therapy, anti-CD20 therapy
24 Enterobacteriaceae:
Biologic Characteristics
- Gram+/-…
- Aerobe/anaerobe…
- Oxidase+/-
- Growth on media
Factoids
- Found in (3)
- Causes…
BC
- Gram-negative rods
- Facultative anaerobes
- Oxidase-negative
- Growth on simple media w/ glucose & on MacConkey agar
F
- Sewage, normal GI flora, feces
- Opportunistic disease
24 Escherichia coli:
Biologic Characteristics
- Differentiation
- Serotypes: O157:H7, K1
Reservoir/Colonizes…
Transmission
Virulence Factors (3)
BC
- O antigen: carbohydrate chain extending from LPS
- H antigen: flagellar
- K antigen: capsular
- O157:H7: EHEC
- K1: neonatal meningitis
R
- People
- Normal GI flora
T
- Person to person
- Contaminated food/water
VF
(1) Fimbrial & afimbrial adhesins
- All produce a common (type 1) pili that attach to mannose receptors
- Pathogenic E. coli have a unique pili (CFA for ETEC) to bind unoccupied receptors
(2) Iron acquisition
- Produce siderophores w/ high affinity for iron
(3) Toxins
- Endotoxin (LPS): outer membrane
- Hemolysin: pyelonephritis
- Heat-stable enterotoxin: increases cGMP
- Heat-labile enterotoxin: increases cAMP
- Shiga toxin: inactivates ribosomes
24 Escherichia coli Biotypes (5):
ETEC: Enterotoxigenic
- Cause…
- Transmitted by…
- Colonize…
- Multiply & produce…
EPEC: Enteropathogenic
- Cause…
- Hallmark
- Adheres to enterocytes using…
- Delivery of…
- Formation of…
- Intimin binding…
- Causes…
EAEC: Enteroaggregative
- Adheres to enterocytes as…
- Increases…
- Makes…
- Causes…
EIEC: Enteroinvasive
- Resembles…
- Causes disease by…
- Lacks…but has…
- Causes…
EHEC: Enterohemorrhagic
- Causes…
- Transmitted via…
- Pathogenesis
ETEC
- Watery diarrhea in infants and travelers & food poisoning
- Ingestion of contaminated food/water
- Small intestine using unique pili (CFAI, II and III) that are plasmid-encoded
- STa and/or LT, increasing intestinal fluid secretion
EPEC
- infant diarrhea in developing countries
- formation of attaching and effacing (A/E) lesions
- plasmid-encoded bundle-forming pilus (bfp)
- effectors (via a type III secretion system) to stimulate signal transduction pathways
- “Pedestal” to deliver a TIR receptor
- to TIR associates pedestal w/ enterocytes
- watery diarrhea
EAEC
- Aggregates
- Mucus production, trapping bacteria in a biofilm
- EAST (an enterotoxin)
- Diarrhea in HIV+ individuals in developing countries, watery discharge, inflammation, & low-grade fever
EIEC
- Shigella
- invading enterocytes, lysing endocytic vesicles and escaping into the cytoplasm, multiply and cause cell destruction
- Lack known specific pili, but do have common pili, afimbrial adhesions, & a type III secretion system
- watery diarrhea, sometimes with blood and fecal leucocytes
EHEC
- Hemorrhagic colitis, bloody stool, uremic syndrome (acute kidney failure) mostly in children
- ingestion of foods (esp undercooked meat) & petting zoos or infected animals
- Adhere via intimin, produce Stx, absorbed into the circulation, affects kidneys
24 Escherichia coli:
Community-acquired vs. nosocomial UTIs
Virulence factors of uropathogenic E. coli (5)
Neonatal meningitis
Diagnosis (2)
Prevention/Treatment (4)
E. coli cause ~80% of community acquired bacterial UTIs but only ~20% of nosocomial UTIs
- Include both cystitis & pyelonephritis
- Highest risk: sexually-active women
- Type 1 (common) pili
- P-pili (pap pili): associated w/ pyelonephritis, binds to P blood group (Forssman) antigen on kidney
- Hemolysin
- Endotoxin
- Can be invasive
Caused by K1 antigen
- Homopolymer of sialic acid
- Inhibits phagocytosis & complement activation (molecular mimicry)
- MacConkey agar (pink colonies due to lactose utilization)
- Differentiation b/n biotypes based on serotyping, clinical grounds, & molecular testing
- Sanitary/hygienic behavior
- Symptomatic (most)
- Antibiotics (neonatal meningitis & UTIs)
- Kidney dialysis & blood transfusion (no antibiotics) for HUS
24 Helicobacter pylori:
Biological Characteristics
- Type
- Motile/Non-motile
- Aerobe/Anaerobe
- Urease
Reservoir/Transmission
Virulence Factors
- Colonization (2)
- Disease (4)
Pathogenesis & Disease
- Most
- Some
- Few
Diagnosis (2)
Treatment
BC
- Curved, gram- rod
- Motile
- Microaerophile
- Urease+
R/T
- Human reservoir
- Fecal-oral or oral-oral transmission
VF
- Urease & flagella (for higher pH)
- VacA, cag pathogenicity island (type IV secretion system & CagA), LPD, & inflammation/urease
P&D
- Mild GI inflammation (chronic gastritis)
- Duodenal or gastric ulcers due to inflammation (ammonia/urease, VacA, CagA)
- Gastric cancer or lymphoma
D
- Biopsy via endoscopy (expensive, invasive, can exclude malignancy)
- Breath tests (radioactive label, noninvasive, cheap)
T
>1 antimicrobial (e.g., clarithromycin and bismuth salts) and an acid blocker (e.g., omeprazole)
