Microbiology Flashcards
What are HAI?
Infections which occur within a certain period from contact with healthcare
~8% of patients in hospitals have an HAI in UK
Worldwide: 3.5-10.5% of hospitalised pts in industrialised countries; ~>25% in developing nations
We can categorise it based on organism:
- –MRSA
- –C. difficile
- –E. coli
- –MSSA
- –R Gram negs
- –Yeasts / Candida
Or by syndrome:
- Catheter associated BSI
- Urinary cath assocd UTI
- Surgical site infection
- Vent assocd pneumonia
- Antibiotic assocd diarrhoea
What is the impact of HAI?
Cost
- Enormous – social / clinical / economic
- UK: £1 Billion a year*
- probable underestimate, very outdated, but often quoted
- In 2004 DH estimate 300,000 HAI per year
Preventable?
- Probably 15-30%
- Financial incentives to prevent – non reimbursement
- US leading the way
- UK and others following
- Unintended consequences
Perceptions of HAI
- dirty hospitals
- poor staff practise
- affects pts who attended hospital for unrelated problems
What are the different types of HAI?
They come from the microbiome of patients and staff, as well as the environment
What are the key strategies for infection control?
Reducing the number of bugs:
- On equipment: sterilisation of equipment prior to operation
- On environment: cleaning = dilution / reduction but not eradication
- On patient: washing, skin preparation pre-op, prophylaxis for contaminated procedures
- On staff hands: hand cleaning after contact any surface
- On staff skin: ??
Reducing number of resistant bugs:
- Screen patients – segregate those with organism detected from those in whom not detected
- for certain organisms, evidence of organism burden reduction with topical suppression
Reduce transmission of bugs:
- Staff - understand and use hand cleaning
- Staff - cleaning environment and equipment
- Staff - reduce use of broadest spectrum antibiotics and of unnecessary antibiotics
- Systems - better design of surfaces with preventing adherence and transmission in mind
What are surgical site infections and what affects them?
3 things that affect SSI:
Host defence, wound environment and pathogens
What are the challenges for outbreak control measures?
- §Improved screening and isolation, impact of delays to typing results
- §Laboratory and epidemiological investigations
- §Internal and external communications. Coordinating briefing and discussions with external stakeholders.
- §Input from other Trusts addressing CRE
- §Hand hygiene and equipment focus, ward based adherence monitors
- §Environmental cleaning and disinfection, attention to pillows and mattresses, HPV usage
- §External reviews and visits of clinical areas
- §Antimicrobial usage and stewardship
- §Expediting discharges
How are HAIs changing over time?
- •Invasive procedures
- •Prosthetic and implantable devices
- •Obesity
- •Diabetes
- •Extremes of age
- •Immunosuppression
- •Emerging organisms/ resistance
Hospital environment
- •Environmental hygiene and cleaning
- eg C. difficile, Norovirus, Acinetobacter outbreaks
- chlorine agents; use of vapourised Hydrogen peroxide
- •Control of environmental sources
- Water: Legionella- cooling towers; Pseudomonas – all water; unusual Mycobacteria – all water
- Building works – Aspergillus
- •Negative pressure isolation – protection of others from an infectious patient with airborne infection
- •Positive pressure isolation – protection of transplant patients from organisms from outside the room
Resistance:
- •Widespread, prolonged use of antibiotics
- •Broad spectrum antibiotics
- •MRSA / VISA / VRE
- •ESBL
- •Multi-resistant / pan-resistant gram negatives
What is gastroenteritis and diarrhoea?
- Gastroenteritis - A rapid onset diarrhoeal illness, lasting less than 2 weeks ¡with diarrhoea (loose and unformed stool) three or more times a day or at least 200 g of stool which is either viral or bacterial in aetiology
- Diarrhoea – loose, or watery stool at least 3x in 24hrs: acute (less than 14d due to viral/bacterial), persistent (14-29d), chronic (>30d due to parasites and non-infectious aetiology should be excluded)
¡Small bowel diarrhea- often watery, associated with crampy abdominal pain and of large volume with bloating and gas. Accompanying fever and blood or inflammatory cells in the stool are rare.
¡Large bowel diarrhea –small volume painful stool which occur often with blood, mucus and inflammatory cells found in the stools and an accompanying fever.
What are the risk factors for gastroenteritis?
- Food bourne
- Exposure related – outbreak situation; travel hx (resource poor setting, cruise, recreational water facilities); occupational/healthcare exposure (c. diff); animal contacts (petting zoos/farms); reptiles (salmonella types with snakes and turtles) or other house pets with diarrhoea; institution/childcare facility
- Host related – immunosuppressed, young children/elderly; men who have sex with men; haemochromatosis; ano-genital/oral-anal/digital anal contact; haemochromatosis or haemoglobinopathies
What is the epidemiology of gastroenteritis?
- Underreporting of GI infections
- Incidence of bacterial GE is less than viral GE and varies in countries and rural vs urban settings
- Most are self limiting <24 hours, patients do not seek healthcare
- Developing countries-outbreaks, cholera especially in war torn countries with no access to clean drinking water and sanitation
- Most vulnerable groups: Infants, elderly, men who have sex with men, immunocompromised
- Reportable: Campylobacter, Salmonella, Shigella, E.Coli 0157, Listeria, Norovirus
What are the mechanisms of disease in gastroenteritis?
3 types of disease:
Secretory diarrhoea - toxin production: cholera toxin, superantigens
Inflammatory diarrhoea
Enteric fever
inflammatory is exudative and enteric fever has interstitial inflammation
What is the method of disease of cholera?
Cholera toxin -
cAMP: opens Cl channel at the apical membrane of enterocytes
>> efflux of Cl to lumen; loss of H2O and electrolytes
Efflux of water and ions which the body can’t keep up with replacing
What are examples of superantigens?
In secretoy diarrhoea - toxin production: superantigens are produced
Superantigens bind directly to T-cell receptors and MHC molecules; outside the peptide binding site
>> massive cytokine production by CD4 cells ie systemic toxicity and suppression of adaptive response
What is the difference in mechanism of disease between inflammatory diarrhoea and enteric fever?
Host responses in bacteraemia:
Inflammatory (exudative ) diarrhoea Vs Enteric fever; interstitial inflammation
How can we diagnose gastroenteritis?
- Stools taking shape of container tested with culture dependent or independent methods with PCR
- Enteric fever – blood and stool tested with culture dependent and independent methods, bone marrow, duodenal fluid and urine also tested
- Stools for microscopy and culture requested where enteric infection suspected
- Stools for bac/viral/parasitic infection tested irrespective of blood in the stool, inflammatory markers or presence of fever or systemic syx if there is suspicion of an outbreak and if tested with molecular methodology, should be followed by culture for public
- Can also tx based on the clinical feature -> each feature is specifically associated with a specific pathogen
What are the extraintestinal manifestations of gastroenteritis and their causative organisms?
•Aortitis, osteomyelitis, deep tissue infections
–Salmonella, Yersinia
•Haemolytic anaemia
–Campylobacter Yersinia
•Glomerulonephritis
–Shigella, camp, Yersinia
•HUS
–STEC, shigella dysenteriae type 1
•Erythema nodosum
–Yersinia, camp salmonella shigella
•Reactive arthritis
–Salmonella, shigella, camp, Yersinia, giardia, cyclospora
•Meningitis
–Listeria, salmonella
What is Staph aureus?
- •1/3 population chronic carriers, 1/3 transient
- •Spread by skin lesions on food handlers
- •Catalase, coagulase positive Gram positive coccus
- •Appears in tetrads, clusters on Gram stain
- •Yellow colonies on blood agar
- Produces enterotoxin, an exotoxin that can act as a superantigen in the GI tract, releasing IL1 and IL2
- Causing prominent vomiting and watery, non bloody diarrhoea
- Don’t treat, self limited
What is Bacillus cereus?
Gram positive rod - spore forming
Found commonly in reheated fried rice
- •Heat stable emetic toxin -not destroyed by reheating
- •Heat labile diarrhoeal toxin - food is not cooked to a high enough temperature
and
- •watery non bloody diarrhoea; self limited
- •Rare cause of bacteremia in vulnerable population
- •Can cause cerebral abscesses
What are clostridia?
Clostridium botulinum : botulism
- •Source : canned or vacuum packed food (honey / infants)
- •Ingestion of preformed toxin (inactivated by cooking)
- •Blocks Ach release from peripheral nerve synapses
- •Treatment with antitoxin
Clostridium pefringens : food poisoning
- •Source : reheated food (meat) like Cosmos
- •Normal flora of colon but not small bowel, where the enterotoxin acts (superantigen)
- •Incubation 8-16hrs
- •Watery diarrhoea, cramps,little vomiting lasting 24hrs
Clostridium difficile: pseudomembranous colitis
- •3%, 30% of hospitalised patients
- •It isn’t an invasive disease and non-toxin producing strains don’t cause disease but can colonise the gut and asyx shedders of spores can act as reservoir to infection
- •2 toxins: A enterotoxin, B is cytotoxin
- •A causes inflammation with intestinal fluid secretion and damage to mucosa
- •B more potent than A and is a virulence factor
- •Antibiotic related colitis (any but.. mainly cephalosporins, cipro and clindamycin)
- •Infection control and preventions precautions required
- Treatment : (PO) metronidazole, vancomycin, stop antibiotics where possible
What is listeria monocytogenes?
- •Outbreaks of febrile gastroenteritis
- •ß haemolytic, aesculin positive with tumbling motility
- •Source : refrigerated food (“cold enhancement”),i.e. unpasteurised dairy, vegetables
- •Grows at 4 ºC
- •GI: watery diarrhoea, cramps, headache, fever, little vomiting
- •Perinatal infection, immunocompromised patients
- •Treatment : ampicillin
What are enterobacteriacae and give an example organism?
Facultative anaerobes, glucose/lactose fermenters (LF), oxidase negative
Escherichia coli :
- •Traveller’s diarrhoea
- •Source: food/water contaminated with human faeces
- •Enterotoxins :
- -Heat labile stimulates adenyl cyclase and cAMP
- -Heat stable stimulates guanylate cyclase
- -Act on the jejeunum, ileum not on colon
Types of e. coli
- •Enterotoxigenic ETEC; toxigenic, main cause of traveller’s diarrhoea
- •Enteropathogenic EPEC; pathogenic, infantile diarrhoea
- •Enteroinvasive EIEC; invasive, dysentery
- •Enterohaemorrhagic EHEC; haemorrhagic O157:H7 EHEC: shiga- like verocytotoxin causes HUS
- •Avoid antibiotics – not beneficial for toxin process
-
What are salmonellae bacteria?
- Non lactose fermenters,
- H2S producers,
- TSI agar,
- XLD agar,selenite F broth
- Antigens:
- -cell wall O (groups A-I)
- -flagellar H
- -capsular Vi (virulence, antiphagocytic)
•Three species :
- -S. typhi (and paratyphi)
- -S.enteritidis
- -S.cholerasuis
What are shigellae bacteria?
- Non lactose fermenters, non H2S producers, non motile
- Antigens:
- -cell wall O antigens,
- -polysaccharide (groups A-D) : S.sonnei, S.dysenteriae,
S.flexneri (MSM)
- •The most effective enteric pathogen (low ID 10-100)
- •No animal reservoir
- •No carrier state
•Dysentery
- invading cells of mucosa of distal ileum and colon
- producing enterotoxin (Shiga toxin)
- Abdo pain and watery diarrhoea
Avoid antibiotics (ciprofloxacin if required)
What are vibrios?
•Curved, comma shaped, late lactose fermenters, oxidase positive.
Treat with doxycycline
Vibrio cholerae
- •O1 group: epidemics, biotypes El Tor, Cholerae and serotypes Ogawa, Inaba, Hikojima
- •Non O1 group: sporadic or non pathogens
- •Transmitted by contamination of water and food from human faeces ( shellfish, oysters, shrimp)
- •Colonisation of small bowel and secretion of enterotoxin with A and B subunit, causing persistent stimulation of adenylate cyclase
- •Causes massive diarrhoea (rice water stool) without inflammatory cells
- •Treat the losses
•Vibrio parahaemolyticus
- -Ingestion of raw or undercooked seafood (ie oysters),
- -major cause of diarrhoea in Japan..or when cruising in the Carribean.. ,
- -self limited for 3 days
- -cholerae : grows in salty 8.5% NaCl..
•Vibrio vulnificus
- can cause diarrhea, but isolated from blood and tissues of septic patients
- cellulitis in shellfish handlers
- fatal septicaemia with D+V in HIV patients
What are campylobacter?
- •Curved, comma or S shaped
- •Microaerophilic
- •C.jejuni at 42 ºC
- •oxidase pos ,motile
- •Self limiting but symptoms can last for weeks (20 days)
- •Transmited via contaminated food and water with animal faeces
- •Only treat if immunocompromised (macrolide)
- •Transmitted via contaminated food and water with animal faeces ( poultry, meat,unpast. milk)
- •Watery foul smelling diarrhoea, bloody stool, fever and severe abdo pain
- •Loose stools occur >10x a day, bloody from 2/3rd day forwards
- •? Enterotoxin (watery diarrhoea) ? Invasion (+/- blood)
- •Treat with erythromycin or cipro if in the first 4-5days
- •GBS syndrome, reactive arthritis, Reiter’s ..
What is Yersinia enterocolitica?
Non lactose fermenter, prefers 4ºC “cold enrichment”
Transmitted via food contaminated with domestic animals excretions
enterocolitis
mesenteric adenitis
associated with reactive arthritis , Reiter’s
What is entamoeba histolytica?
- motile trophozoite in diarrhoea
- non motile cyst in nondiarrhoeal illness
- Killed by boiling, removed by water filters
- 4 nuclei
- No animal reservoir
Ingestion of cysts >> trophos in ileum >> colonize cecum, colon >> “flask shaped” ulcer
- -dysentery, flatulence, tenesmus
- -chronic : wt loss,+/- diarrhoea
- -liver abscess
Diagnosis
- -stool micro (wet mount, iodine and trichrome )
- -serology in invasive disease
Treat : metronidazole + paromomycin in luminal disease
What is Giardia lamblia?
- trophozoite “pear shaped”
- 2 nuclei
- 4 flagellas and a suction disk
- Ingestion of cyst from fecally contaminated water,food
- •Excystation at duodenum
- •tropho attaches
- •no invasion
- •malabsorption of protein and fat
- At risk: Travellers, hikers, day care, mental hospitals, MSM
- foul smelling non bloody diarrhoea, cramps, flatulence, no fever
- Diagnosis : stool micro, ELISA, “string test”
- Treatment :metronidazole
What is cryptosporidium parvum?
Parasite
- Infects the jejunum
- Severe diarrhoea in the immunocomromised
- Oocysts seen in stool by modified Kinyoun acid fast stain
Treatment : reconstitution of immune system
What is norovirus?
- outbreaks
- Low ID (18-1000 viral particles)
- Environmental resilience (0-60 ºC)
- No long term immunity
- GII.4 currently predominant strain
What are the 3 targets for antibiotics?
- Peptidoglycan layer of cell wall (1)
- Inhibition of bacterial protein synthesis (2) (ribosome is different in prokaryotes)
- DNA gyrase and other prokaryote-specific enzymes (3) (not present in eukaryotes)
What are the differences between GNB and GPB?
- Gram positive cell wall (thick peptidoglycan layer) LEFT
- Gram negative cell wall (has outer membrane, which is why they are more multidrug resistant) RIGHT
Give examples of cephalosporins
- MRSA, C. diff -> problems with resistance
- cefuroxime – Stable to many β-lactamases produced by Gram negatives. Similar cover to co-amoxiclav but less active against anaerobes
- ceftriaxone – 3rd generation cephalosporin. Associated with C. difficile
- ceftazidime – anti-Pseudomonas mostly
- Extended Spectrum β-lactamase (ESBL) producing organisms are resistant to all cephalosporins regardless of in vitro results
What are glyopeptides as antibiotics?
- Large molecules, unable to penetrate Gram –ve outer cell wall
- Active against Gram +ve organisms
- Inhibit cell wall synthesis
- Important for treating serious MRSA infections (iv only)
- Oral vancomycin can be used to treat serious C. difficile infection
- Vancomycin and Teicoplanin are examples of glycopeptides
MoA: Stop the transpeptidase from binding, no cross links forming, don’t let transglycosidase from binding – weakened cell wall causing the cells to die
- Slowly bactericidal – not as active as b-lactams, which are usually first choice
- Nephrotoxic – hence important to monitor drug levels to prevent accumulation
What are aminoglycosides?
- Bind to amino-acyl site of the 30S ribosomal subunit
- Rapid, concentration-dependent bactericidal action (need a high concentration for it to work properly)
- Require specific transport mechanisms to enter cells (accounts for some intrinsic R)
- Ototoxic & nephrotoxic, therefore must monitor levels – check levels in blood to check for accumulation, high trough levels which causes the toxicity
- Gentamicin & tobramycin particularly active vs. Ps. aeruginosa
- Synergistic combination with b-lactams (try to use b-lactams alone mainly)
- No activity vs. anaerobes (useful with chloroforms)
MoA:
Bind to the 30S ribosome and prevent elongation of the peptide chain; but doesn’t show why they are bacteriacidal
What are tetracyclines?
- Broad-spectrum agents with activity against intracellular pathogens (e.g. chlamydiae, rickettsiae & mycoplasmas) as well as most conventional bacteria – don’t have a cell wall, most MRSA not resistant to it
- Bacteriostatic
- Widespread resistance limits usefulness to certain defined situations
- Do not give to children or pregnant women
- Light-sensitive rash – especially in the sun
What are macrolides?
- Bacteriostatic
- Minimal activity against Gram –ve bacteria
- Useful agent for treating mild Staphylococcal or Streptococcal infections in penicillin-allergic patients
- Also active against Campylobacter sp and Legionella. Pneumophila – b-lactam with a macrolide for pneumonia tx to cover the atypicals
- Newer agents include clarithromycin (long t ½) & azithromycin (good with gram negatives) with improved pharmacological properties
MOA: Can prevent toxins being produced, which is good for group A strep and nectrosing fasciitis, which would be added to a b-lactam, so you can add macrolides to prevent the toxins in severe skin infections
What is chloramphenicol?
- Bacteriostatic
- Very broad antibacterial activity
- Rarely used (apart from eye preparations and special indications) because risk of aplastic anaemia (1/25,000 – 1/45,000 patients) and grey baby syndrome in neonates because of an inability to metabolise the drug
- Tx of choice for meningitis; not associated with c.diff diarrhoea
MOA:
•Chloramphenicol binds to the peptidyl transferase of the 50S ribosomal subunit and inhibits the formation of peptide bonds during translation
What are bacterial mechanisms of resistance?
- Chemical modification or inactivation of the antibiotic – b lactams
- Modification or replacement of target
- Reduced antibiotic accumulation
1) Impaired uptake
2) Enhanced efflux
•Bypass antibiotic sensitive step
How does the influenza virus adapt from a bird flu to become pathogenic to humans?
Fristly: needs activation by host cell proteases only expressed in respiratory tract -> hence why causes respiratory disease
Influenza generates haemagluttinin which needs to be cut into 2 pieces is found in respiratory section of lung – human airway tryptase -> then can cause this multiplication, propagation and spread
These viruses are very pathogenic in chickens which then replicate very rapidly, leading to v severe disease and can detect the virus outside the lungs, in the blood -> due to cleavage of haemagglutinin
H7N9 avian influenza in China: Not highly pathogenic at the beginning – just restricted at first to a specific part of the body; series of waves of pandemic – emergence of highly pathogenic multibasic cleavage protein had appeared -> due to a massive poultry vaccination project the number of infected have decreased completely
Infection of humans with unadapted avian influenza virus can lead to hypercytokinaemia
What are the 3 factors needed for influenza to become a pandemic?
•A pandemic virus will have novel antigenicity.
•A pandemic virus will replicate efficiently in human airway.
•A pandemic virus will transmit efficiently between people.
1918 influenza virus and all subsequent human viruses of 20th century have PB2 627K . Replication can be achieved by a single amino acid change in polymerase PB2 E627K; human infections with avian flu associated with severe disease carry pb2 e627k mutation -> a few days after infection the flu will switch to this mutation as it is essential to replicate and adapt to grow in human airway; severe ones such as H5N1 and H7N9 infections
H5N1 and H7N9 and influenza viruses still don’t infect humans properly; but the mutation can occur in 1 of 2 ways -> acquire as it replicates in the airway OR in influenza is segmented, meaning the genome of the virus, which means that if 2 different viruses nter the same cell, the virus leaving can contain genetic material from both called REASSORTMENT!
This is what led to the swine flu -> H3N2; these viruses still need further reassortment and adaptations of their haemagglutinins
Transmission:
- Via droplet - aerosol or fomite (drop on object)
- Features which affect transmission: Receptor binding, virion stability and NA stalk length
- Avian influenza bind to syalic acids which are bound to the alpha 2 linkage;
- in resp tract we have more alpha 6 linkage, so won’t bind and enter that cell very efficiently;
- unless it mutates and changes the haemagglutinin which changes preference to alpha 2,6 receptor;
- also needs to be stable to be able to survive in water droplets, as they get more and more concentrated - mutations of haemagg which can stabilise the whole haem which canmaintain air borne transmission
- Neuraminidase tends to be short in length in chicken adapted viruses, very long in human mucous barriers, to reach the human airway cells -> if all 3 happen then we can have the next pandemic -> in h5/h7/h10-13 who knows?
What happened with Swine flu pandemic in 2009?
- Nearly 9000 hospitalizations in the UK, more than 800 deaths
- Globally 200,000 deaths
- Seropositivity in London and Birmingham >40% in children by September 2009 (Miller et al. 2010)
- Case fatality ~ 0.02%
- Mild disease in majority of cases.
- 50% of those hospitalized were previously healthy (FLUCIN Thorax 2010).
Elderly were relatively spared -> most of those affected were between 0-5 and 15-44
Inherited the gene from the 1918 Spanish flu, which infected some pigs and stayed within pigs for decades -> pigs don’t live for very long, so not much selective pressure so the virus remained evolutionary static; hence why the elderly popn had immunity to this flu
Reasons why there were severe outcomes from swine flu H1N1 ->
- •High dose, route of exposure
- •Mutant virus (D225G mutation in HA associated with 25% fatal cases in Norway)
- •Bacterial superinfection (Odds ratio of 125 after other factors accounted for in Argentinian study)
- •Co morbidity: Asthma, pregnancy, obesity, diabetes
- •Genetic predisposition: IFITM3 mutation - loss of gene linked with severe influenzza, the CC variant of it; ethnic bias
Quite often the 3rd wave is even more severe – maybe due to the virus mutating and then by the 3rd wave it has improved so much that it can now spread much faster; OR could be in 2011 the winter was much colder
What are the different pathologies of diarrhoeas according to incubation period?
longer than a day then think about enteric bacteria; stool bloody and secretory; more chronic = parasites and c.diff
How do transplants cause immunosuppression?
Both have a period of time where the IS is turned off -> level of immunosuppression required -> solid organ patietns need continued immunosuppression, but stem cell can eventually reduce their levels and have a normal life
Epidemiological exposure in transplant recipients:
- Virus acquired from graft like HBV- serostatus and risk assessment; usually occurs within 4 weeks from transplant
- Virus reactivation from host like HSV - serostatus, monitoring, prophylaxis, pre-emptive therapy; usually occurs between 1-12m from transplant. Examples:
- adenovirus, EBV, hepB/C, HSV, HHV6/7, VZV kind of
- Novel infection from infected individual like VZV - isolation barrier nursing, advice for family/contacts, post-exposure prophylaxis, vaccinating contacts, control of diet; occurs 12m after transplant
- respiratory viruses CMV, HPV, JC virus, PML, PTLD, VZV
The development of infections in solid organ transplantation vs bone marrow transplants are different, with solid organ transplants having a longer timescale for infection 1-6m and encompasing bacteria from wound/UTI; opportunistic infections such as CMV, MTb, listeria, candida.
Bone marrow transplants have a much shorter timescale over 1-4m, with most infection occurring in the first few months: GNR bactaraemia, HSV, CMV, oral candidia, deep candidiasis, aspergillosis; parasites: pneumocystis, toxoplasma, VZV
List of serology done before transplantation – need to monitor the infections which occur later on – know that they are going to get adeno more common, that’s why need to check for this one
CMV monitoring or prophylaxis; EBV monitoring; Adeno monitoring (paeds BMT); HSV prophylaxis if indicated
- •HIV Ag/Ab
- •HBV sAg
- •HBV cTAb
- •HBV sAb
- •HCV Ab
- •EBV IgG
- •CMV IgG
- •HSV IgG
- •VZV IgG
- •HTLV Ab
What is hepatitis B?
The virus is one of the smallest enveloped animal viruses, but pleomorphic forms exist, including filamentous and spherical bodies lacking a core. These particles are not infectious and are composed of the lipid and protein that forms part of the surface of the virion, which is called the surface antigen and is produced in excess during the life cycle of the virus.
The core protein is the major component of the nucleocapsid. HBeAg may be generated from the core protein by proteolytic cleavage.
HBsAg will increase, but as resistance increases, the virus is cleared so the Ag decreases
•Two things can happen:
- –Carriers may have flare of disease.
- –Those who have had past infection can reactivate
- •The risk of reactivation is particularly important with patients on B-cell depleting therapies (i.e Rituximab)
- –Might not have cleared it in the first place, depleted their cells
•Prevention:
- –Nucleoside/nucleotide analogues (eg lamivudine, tenofovir, entecavir) prophylaxis -> viricidal drugs to kill hepB
