Viral Pathogens: Hepatitis Flashcards
Hepatitis B Virus
Belongs to the virus family Hepadnaviridae and DNA
- unusual partially double-stranded circular small DNA genome
- abdominal tenderness (pain or discomfort when an affected area is touched)
Abdominal guarding
tensing of abdominal wall muscles to guard inflamed organs within the abdomen from the pain of pressure upon them
Hepatitis B Virus Structure
4 Open Reading Frames (ORFs)
ORF C
encodes the core antigen (HBcAg) which forms a protective Nucleocapsid around the genome
ORF S
encodes the surface antigen (HBsAg)
-composed of large,middle and small surface proteins present in the envelope
ORF P
encodes the polymerase enzyme
- has both DNA and RNA-dependent polymerase activities
ORF X
encode the X antigen, which is known to act as a Transactivator of transcription
-likely involved in carcinogenesis
A transactivator gene
express a transcription factor that binds to a specific promoter region of DNA
- causes that gene to be expressed.
When ORF C and Pre C are translated together:
result is HBeAg
-indicator of active viral replication.
HBV enters a new host via
genital tract or following direct inoculation of virus into the bloodstream
Where does HBV travel once within the blood?
the virus travels to the liver, where it infects the Hepatocytes
What does HBV do once within the liver cell?
the virus replicate, and new virus particles are released directly into the bloodstream
-gain access to every bodily compartment
Open Reading Frames (ORF)
part of a reading frame that has the potential to be Transcribed
-continuous stretch of codons that contain a Start codon (AUG-Methionine) and stop codon (UAA, UAG, UGA)
What are the three routes Hepatitis B virus is spread from person to person?
- vertical transmission (mother to baby)
- sexual transmission
- direct blood to blood transfer of virus (parenteral transmission)
WHO estimates there are around _____ ______ of _____ carriers and ___ _____ in the _____
WHO estimates that worldwide there are around 350 millions of HBV carriers and 1.2 million in the USA
What are the three groups the WHO classifies countries into according to their rate of HBV carriage?
- High: over 8 % of countries population are carriers
- Intermediate: 2-7%
- Low: under 2%
Host response to infection: Innate immunity
early stages of infection within the liver, there is IFN induction and NK cell activity.
Host response to infection: Adaptive immunity
virus encodes a number of distinct Ags
- HBsAg
- HBcAg
- HBeAg: soluble protein released from infected cells, indicates active viral replication
Why is the production of anti-HBs antibodies important?
enabling the host to overcome the infection and eliminate the virus (Neutralizing Antibodies).
Cellular immune response
lead to virus-specific Cytotoxic CD8+ T lymphocytes (CTLs) -able to kill infected hepatocytes through recognition of viral antigens present on the infected cell surface in association with HLA class I moleucles
pathogenesis
host CTL response killing infected cells, in this way-HBV replication within hepatocytes of itself is not cytolytic and does not result in death of infected cells.
- how most damage to hepatocytes in HBV is thought to arise
HBV clinical presentation
- 55-60% of acute HBV infections are asymptomatic (subclinical infections)
- 1% result in fulminant hepatitis (acute liver failure)
- 5-10% fail to clear infection and become chronic carriers
Symptoms of acute hepatitis B
- feeling sick (malasie)
- vomiting
- abdominal pains
- fever
- jaundiced (eyes/skin)
- dark urine and pale feces
In over _ out of 10 cases in adults, virus is cleared from the body by the ______ system within _ to _ months
9, immune. 3-6
In over _ out of 10 newborns infected from their mothers, virus remains ____
9, long term
Chronic HBV infection
proportion of patients (5-10% of adults) infected will fail to eliminate virus from liver
In chronic infection:
virus continues to replicate in infected hepatocytes
-continuously released into bloodstream
Chronic carriers are the
source of infection
cirrhosis
over time continual death of liver cells and their replacement by fibrous tissue results in complete loss of normal liver architecture and function
What is the average time from acute infection to cirrhosis?
20 years
What is another complication of chronic HBV?
development of hepatocellular carcinoma (HCC)
- malignant proliferation of hepatocytes
- HBV carriers are 300 times more likely to develop than individuals who aren’t carriers
HBV diagnosis
depends on detection of various markers of infection
-detect HBsAg in blood sample (positve=HBV infection)
core Ag
anti-HBc
-used to distinguish between Acute and chronic infection
acute infection
HBsAg+, IgM anti HBc +
-followed to see if they eliminate the viurs over following 6 months (disappearance of HBsAg and appearance of anti HBs)
If _____ persist for longer than __ months, patient is a ____ carrier
HBsAg, 6, chronic
The HBeAg/anti-HBe system distinguishes between two types of carrier
HBeAg+ are extremely infectious
- Anti-HBe carrier is much less infectious, and at much lower risk of chronic liver disease
- Anti-HBs arises in patients who clear infection and are vaccinated
No specific management for acute HBV infection
bed rest and avoid alcohol
In case of fulminant hepatitis what may be the only resort?
liver transplant
Carriers of HBV should be advised that
they’re potentially infectious
-No blood donations, share razors or toothbrushes
HBV vaccination
using the HBsAg as the immunizing
agent
-three intramuscular injections, the second and third administered 1 and 6 months after the first
-last for around 20 years
- provides greater than 90-95% protection to infants, children, an
Human Coronavirus
Enveloped non-segmented positive-sense RNA
-Named for the crown-like spikes on their surface
- First identified in 1965
-Broadly distributed in humans and other species – bats, birds, rabbits, reptiles, cats, dogs, pigs, and monkeys
-Spread by aerosol droplets and contact with infected secretions
-Survival outside the body:
+1-2 days on non-porous surfaces (e.g. hard surfaces)
+8-12 hours on porous surfaces (e.g. soft goods)
Community-acquired human coronaviruses (HCoVs)
- 229E (alpha coronavirus)
- NL63 (alpha coronavirus)
- OC43 (beta coronavirus)
- HKU1 (beta coronavirus)
Other human coronaviruses
- severe acute respiratory syndrome coronavirus (SARS-CoV)
- Middle East respiratory syndrome coronavirus (MERS-CoV)
- 2019 novel coronavirus (SARS-CoV 2) causes COVID-19
Community acquired Human coronaviruses (HCoVs)
- worldwide distribution
- more common in winter and spring
- responsible for 20% of common colds
- symptoms in 50-90% of persons infected
- more common in children
- reinfection is common due to rapid diminution of antibody levels
Severe Acute Respiratory Syndrome coronavirus (SARS-CoV)
- first recognized in china in November 2012
- caused worldwide outbreak in 2012-2013
- probable cases 8,098
- deaths=774(10%)
- no cases since 2014
- originated in bats
- transmitted to humans through civets
Middle East Respiratory Syndrome coronavirus (MERS-CoV)
- first reported in Saudi Arabia in 2012
- reported in 27 countries all near Arabian peninsula
- confirmed cases 2,494
- deaths 858
- likely originated in bats
- transmitted to humans through camels
ACE2
Angiotensin-Converting enzyme 2 receptor
-helps modulate the many activities of angiotensin II (ANG II) increases blood pressure, tissue injury and inflammation
ACE 2R
lung, heart, kidney, blood vessels, liver and gastrointestinal tract
COVID-19 clinical presentation
- incubation period 2 to 14 days (average 8 days)
- basic reproductive number R0=2.77
- fever (83-98%) may be prolonged and intermittent
- cough (76-82%)
- myalgia and fatigue (11-44%)
- sore throat in some cases
- anosmia (loss of sense of smell)
- headache, fatigue
- aguesuia (diminished sense of taste)
- less commonly: sputum production, headache, hemoptysis and diarrhea
- asymptomatic infection in young individuals
Basic Reproductive Number R0
number of cases that are expected to occur on average in a homogeneous population as a result of infection by a single individual
If the average R0 is greater than 1
The infection will spread exponentially
The _________ the value of
___ , the _______ an epidemic will progress
Higher, R0, faster
COVID-19 clinical course
- variable from asymptomatic infection or mild illness to severe or fatal illness
- dyspnea in ~50% after a median
Between what phases does symptom onset occur in COVID-19?
Incubation period (5.1 days) Acute mild phase (5-10 days)
Acute mild phase
nonspecific symptoms
-most common:fevers, cough, myalgias, fatigue, nausea, diarrhea
COVID risk factors for severe illness
-Older patients >65 years old
-Serious chronic medical conditions such
as:
+Heart disease
+Hypertension
+Diabetes
+Lung disease
+Cancer
+Obesity BMI>30
COVID laboratory findings
In hospitalized patients: Ø Leukopenia (9–25%) Ø Leukocytosis (24–30%) Ø Lymphopenia (63%) Ø ALT and AST levels (37%) Ø Normal serum levels of procalcitonin Ø Chest CT images -Bilateral involvement in most patients -Multiple areas of consolidation and ground glass opacities
What are the types of tests available for COVID-19?
Viral tests and antibody tests
Viral test
tells you if you have a current infection (Molecular and Antigen)
antibody test
might tell you if you had a past infection (serological)
-might not show if you have a current infection because it can take 1–3 weeks after infection for your body to make antibodies