Week 10 Flashcards
Acute Viral Hepatitis
Asymptomatic > symptomatic > fulminant liver failure > death
Nausea, vomiting, abdominal pain, loss of appetite, fever, diarrhea, light colored stools, dark urine, jaundice
Hepatitis A:
- Main features
- transmission
Picornavirus, (+)ss linear RNA, icosahedral, nonenveloped
Main cause of acute hepatitis in US
Low morbidity and mortality, older people tend to be more symptomatic
NO chronic infection
Transmission: fecal-oral transmission
Hepatitis A
Prevention?
pre/post exposure immunization
KILLED vaccine (one serotype)
Can give passive vaccination with antibodies (not recommended)
Hepatitis A
Diagnosis?
IgM anti-HAV (recent infection), Anti-HAV IgG (past infection or vaccine, lifelong immunity
Hepatitis B
Main features
hepadnavirus, enveloped
Partially DS circular DNA
Neutralizing abs to surface antigen protective (anti-HBsAg)
Hepatitis B
Replication cycle
occurs in nucleus
Host DNA repair machinery “fixes” partially ssDNA genome → cccDNA
Host DdRP Pol II transcribes cccDNA → RNA transcript transported into cytoplasm → HBV pre-genome RNA packaged
HBV pre-genome reverse transcribed by HBV reverse transcriptase → cDNA → virus buds and egresses
**convert to cDNA on the WAY OUT instead of the way in
Hepatitis B
Transmission
parenteral transmission - blood/blood-derived body fluids
Can have mother to infant transmission → chronic infection of infant (prevent infection of infant with active and passive immunization immediately at birth)
Hepatitis B
Prevention
pre/post exposure immunization, vaccine
Hepatitis B
Disease
acute liver disease, chronic liver disease, cirrhosis, HCC
Long incubation period
Chronic infection more likely in kids (<5 yrs), but acute illness LESS likely in younger people (vice versa for > 5 yrs)
HBV surface Ag
HBV surface Ag = antigen on surface of HBV → indicates Hep B infection
Anti-HBsAG antibodies
Anti-HBsAG antibodies→ antibody to HBsAg, indicate immunity to HepB
Anti-HB-core antibodies
Anti-HB-core antibodies → IgM (acute) IgG (chronic or prior infection)
IgM is sole marker of infection during window period
HBeAg
HBeAg = sign of infectivity → Anti-HBeAb = sign of low infectivity
Treatment of HepB (4)
1) INF-a
2) Nucleoside/Nucleotide Analogs
3) Acute infection = SUPPORTIVE
4) Neonate of HBsAg+ mother –> vaccinate
IFN-a
Mechanism in Hep B and C
inhibition of transcription and translation of viral genes
inhibition of glycosylation and maturation of viral proteins
inhibition of liberation of newly synthesized viral particles
IFN-a
ADRs
flu-like syndrome,bone marrow suppression, increased susceptibility to bacterial infections, unmask autoimmune disease
NOT given in pregnancy
Entecavir
nucleoSIDE analog
Inhibits DNA polymerase priming, reverse transcription, and DNA-dependent DNA synthesis
Competes with cellular dGTP for viral DNA polymerase activity
Also used in HIV
Tenofovir
nucleoTIDE analog
Also used in HIV
Must be phosphorylated by cellular kinases to active triphosphate form
Hepatitis C
Main features:
Flavivirus, (+)ss linear RNA, icosahedral, enveloped
Hepatitis C
Disease
Acute infections are usually subclinical
Chronic infection possible - 80% go on to chronic infection
Cirrhosis, liver failure, HCC
Hepatitis C
Transmission
parenteral - blood/blood-derived body fluids
Hepatitis C
Treatment (5)
1) Simeprevir
2) Ribavirin
3) Sofosbuvir
4) Ledipasvir
5) Pegylated IFN-a
Simeprevir - mechanism? ADRs?
NS3/4A HCV protease inhibitor, prevents viral replication
ADRs: photosensitivity reactions, rashes
Used in conjunction with peginterferon and oral ribavirin or sofosbuvir
Ribavirin
purine nucleoside analog
ADRs: hemolytic anemia, NOT given in pregnancy
Sofosbuvir
inhibits HCV RNA-dependent RNA polymerase (NS5B) → chain termination
Used in combination with Ledipasvir
ADRs: fatigue, headache, nausea
Ledipasvir
inhibits NS5A HCV protein essential for HCV assembly, replication, secretion
Used in combination with Sofosbuvir
Hepatitis D
Main features
Delta virus, ss (-) circular RNA virus, enveloped
Hepatitis D
Disease
requires concurrent Hep B infection (particles packaged with HBVsAg)
Increases severity of hepatitis
HDV becomes chronic and persists along with HBV
Hepatitis D
Transmission
percutaneous, permucosal, blood/blood-derived body fluids
HBV vaccine also prevents HDV
Hepatitis E
Main features:
Hepevirus - naked, icosahedral (+) ssRNA
Hepatitis E
Transmission
fecal-oral transmission
**reservoir in pigs/swine = zoonotic
Hepatitis E: Disease?
fulminant hepatitis in pregnant women** (20% mortality)
In other people is acute, self-limiting hepatitis
Hepatitis E
Diagnosis
IgM anti HEV or RT-PCR
Hepatitis E
Prevention
no FDA approved vaccine (vaccine used in China)
Meningitis in newborns (0-6 months) (3)
1) Group B strep
2) E. Coli
3) Listeria
Meningitis in Children (6 months - 6 years) (4)
1) Strep pneumoniae
2) Neisseria meningitidis
3) Haemophilus influenzae type B
4) Enteroviruses
Meningitis in Adults (6-60 years) (4)
1) N. Meningitidis
2) Enteroviruses
3) S. Pneumoniae
4) HSV
Meningitis in Older Adults (60+ years) (3)
1) S. Pneumoniae
2) Gram negative rods
3) Listeria
HAV vaccine vs. HBV vaccine
HAV vaccine: passive human Ig and active (KILLED vaccine)
HBV vaccine: passive (HBIG) and recombinant SUBUNIT (HBsAg) vaccine
Droplet precautions
Isolation of patients infected with organisms that can be transmitted via droplets than can be generated by patient during coughing, sneezing, talking, or during procedures
Private room + mask + hand hygiene
Influenza, RSV, Neisseria meningitidis
Airborne precautions
Isolation of patients with organisms spread via airborne droplet nuclei
Private room + negative pressure + > 6-12 air changes per hour
N-95 mask worn by all persons entering the room
Used for M. TB, measles, primary infection for VZV
Contact precautions
Private room
Use of hand hygiene
Gloves and gowns prior to entry into patient room
Used to prevent spread of MDR organisms (VRE, MRSA, MDR acinetobacter, C. diff)
Dysbiosis
abnormal composition of a microbiome
EX) IBS, antibiotic associated diarrhea, obesity, bacterial vaginosis, “non-bacterial” prostatitis, pouchitis, T1DM, Mother-to-child HIV transmission, MRSA colonization and infection
- Bacterial vaginosis - caused by loss of protective species (lactobacilli) and gain of anaerobes (prevotella, gardnerella)
- Crohn’s Disease: diminished levels of Clostridium and bacteroides species in the gut
Environmental factors that influence patterns of colonization in infants
1) Mode of delivery (C-section vs. Vaginal)
2) Feeding (breast milk vs. formula)
Infant microbiome
Infants born sterile but are quickly colonized by diverse microorganisms
Within weeks, baby has bacterial load of typical adult
Development of immune system occurs in parallel → likely influenced by microbiome
Gut microbiome in human nutrition
Evidence for obesity-predisposing microbiome
Metabolic function of microbiome =
- Ferment non-digestible polysaccharides and mucus
- Synthesize vitamins (B3, B5, B6, B12, K, Biotin, Folate)
- Sequester metals
Pathogen exclusion
commensals compete with pathogens → limit infectivity
Nutrient, receptor competition
Antimicrobial products of commensals (lactic acid, H2O2, pH, bacteriocins)
EX) C. Diff infection after antibiotic use
Immune homeostasis
balance between hyper-reactive / unresponsive immune system
Commensal vs. Parasite vs. Mutualist
Commensal: interaction between two species in which one benefits and one is unaffected
Mutualist: interaction between two species in which both species benefit
Parasite: interaction between two species in which one benefits and one is harmed
Gnotobiotic
growth in a germ-free environment
Microbiome
community of microorganisms inhabiting a particular niche
Aka “commensals’
Neutral or beneficial functions
Found on all exposed surfaces
10 microbes per human cell (10^14 microbes colonize a person), collective microbial genome is 100x human genomes
