Session 10 ILOs - Influenza and E.Coli Flashcards
Describe the structure and replication of the Influenza virus
Structure:
- Spherical, enveloped virus containing a genome of segmented negative-sense RNAs
- Negative-sense RNAs belongs to three types:
A, B, and C
- 2 surface antigens: H and N (haemaglutinin and neuraminidase)
Replication:
- negative single stranded RNA is converted by RNA polymerase (RNA dependent RNA polymerase) into positive single stranded RNA
- It is then further converted back to negative single stranded RNA which is a very close copy to the original
- Also, mRNAs are converted to viral proteins and are assembled into nucleoplasmids
Define the concept of an animal reservoir for type A influenza (including poultry, horses, pigs, and other animals) and its major surface antigens - hemagglutinin (HA) and neuraminidase (NA)
- Animal reservoirs can contribute to antigenic shift - dramatic changes in the antigenic properties of the H and/or N proteins
- This leads to surface antigens from different species (antigenic shift)
- Antigenic shift = major changes in the gene that occur suddenly on combination on 2 or more strains = pandemics!
- Where pigs, humans, birds etc. coexist, it’s possible for an animal to be simultaneously infected with multiple influenza subtypes, which is where reassortants can be produced where the mRNAs for H and N antigens have been reasserted into unique combinations
- Reassortant virus then has the potential to spread among humans
Explain how the influenza virus gains entry to the human host through attachment of the viral HA to sialic acid–containing glycoproteins/glycolipids and subsequent uptake into an endocytic vesicle and is spread from person to person via respiratory droplets that infect the upper and lower respiratory tract
Influenza viruses are transmitted from person to person via the respiratory route
- Small particle aerosols
- Larger particles or droplets
- Viral particles
- Influenza virus binds to the transmembrane protein on the surface called Neu5Ac residues (silica acid) which acts as a receptor
- Entry then occurs immediately via receptor-mediated endocytosis
- The virus can then leave the cell by neuramidase enzyme which cleaves the N protein
Describe the clinical symptoms and complications of influenza infection
Clinical symptoms:
- Headache
- High fever
- Sore throat
- Runny nose
- Muscle aches and pains
Complications:
- Viral pneumonia
- Secondary (bacterial) pneumonia
- Central nervous system syndromes
- Reye syndrome
Describe how you would diagnose flu in a clinical setting
Diagnosis is usually from symptoms and clinical assessment but there are rapid antigen tests and PCR
Briefly outline the management of influenza including treatment options and prevention
Treatment options (2 main ones):
- Antivirals e.g. Rimantadine and Amantadine
- Inhibit viral uncoating after uptake probably through M2 protein so they can’t replicate
- Influenza A only - Neuraminidase inhibitors e.g. Oseltamivir or Zanamivir
- Inhibit viral release from infected cell and cause aggregation of viral particles
- Influenza A and B
Prevention treatment: - Vaccination Children = live attenuated cold adapted Adults = formalin-inactivated - Determined by WHO each year, predicted from the prominent flu strains that year - Given to vulnerable individuals
Define the concepts of antigenic drift and antigenic shift
Antigenic drift = minor changes in the genes that occur over time
- Yearly accumulation of mutations in the H and N proteins (cause seasonal epidemics)
Antigenic shift = major changes in the genes that occurs suddenly when 2 or more different strains combine
- Acquisition of a novel HA and NA by the virus (cause seasonal epidemics)
Define the concepts of pandemics and epidemics (seasonality) and how these may arise in relation to influenza
Epidemics:
- Widespread occurrence of an infectious disease in a community at a particular time, above the normal rate
- Likely to be caused by influenza B
Pandemics:
- An epidemic over a very large area affected a large population of the population, often the world
- Likely to be caused by influenza A
Describe the biology of E. coli including the identification and serology
Serology:
- Gram negative rod (bacteria)
- Can grow anaerobically
- Many serotypes
- Constituent part of large bowel of many animals
Identification:
- Typically lactose-fermenting (you can use MacConkey agar as it contains lactose, which will grow into pink/red colonies if the pH becomes acidic when lactose is broken down into lactic acid)
Describe the role of E. coli in health and disease
Constituent part of large bowel of many animals
Commonly cause urinary tract infections, intestinal infections (eg travel-related diarrhoea), sepsis or neonatal meningitis - in UK, E.Coli is most common because of bloodstream infections
Can potentially protect against pathogenic species such as salmonella
6 main diarrhoea-causing types:
1) Enterotoxigenic E. coli (ETEC) - causes ‘traveller’s diarrhoea’ through the production of 2 toxins (heat stable and heat labile) to cause watery diarrhoea.
2) Enteropathogenic E. coli (EPEC) - creates a translocation tube to access and anchor into the enterocyte.
3) Shiga toxin-producing E. coli (STEC) also called Verocytotoxin-producing E. coli (VTEC) or enterohaemorrhagic E. coli (EHEC). Shiga toxin (A & B subunits) inhibits protein synthesis within the cell and this causes cell death.
4) Enteroaggregative E. coli (EAEC)
5) Enteroinvasive E. coli (EIEC)
6) Diffusely adherent E. coli (DAEC)
Describe E. coli as a cause of diarrhoea including its pathogenesis, role of toxins and clinical features
1) Enterotoxigenic E. coli (ETEC)
Pathogenesis - ETEC produces 2 toxins (heat stable toxin and heat labile toxin), it can produce one or both and the illness caused is similar
Role of toxins - toxins stimulate the lining of the intestines causing them to secrete excessive fluid, producing watery diarrhoea and abdominal cramping
Clinical features - watery diarrhoea, abdominal cramping
Leading cause of travellers diarrhoea
2) Enteropathogenic E. coli (EPEC)
Pathogenesis - creates a translocation tube to access and anchor into the enterocyte
Role of toxins - Binding to membrane bound protein permits EPEC to attach to cells
3) Shiga toxin-producing E. coli (STEC)
Pathogenesis - Shiga toxin (A & B subunits) inhibits protein synthesis within the cell and this causes cell death
Role of toxins - see above
Clinical features - haemorrhagic colitis, haemolytic uraemic syndrome (causes RBCs to fracture around the bloodstream)
Describe E. coli as a cause of urinary tract infections with virulence factors and clinical features
Strains of E.Coli are capable of causing disease outside of the intestinal tract
Virulence factors:
- Adhesins
- Iron sequestration systems (collects iron from the environment and helps growth)
- Protectins and invasins
- Toxins
UTIs:
- Uropathogenic e.coli travel from the rectum to the urethra and migrate to the bladder, causing cystitis
- More common in women
Clinical features:
- Pain on urination
- Increased frequency of urination (increased urges)
Describe E. coli as a cause of blood stream infections and sepsis
E.coli bacteria are the most common because of bacterial bloodstream infection in england
Over half of cases occur in patients older than 75 yrs
- 50% linked to ineffective antibiotic treatment??
- 21% have urinary catheters
- 16% liver/bililary infections
- 7% GI infections
Describe the management of E. coli infections
Prevention and treatment are the 2 main forms of management:
Prevention:
- Avoid foods and drink that could be contaminated with bacteria
Treatment:
- Most infected people will recover within a few days without specific treatment
- Recommend clear liquids and oral rehydration solutions
- Avoid antibiotics!
- UTIs specifically, use Trimethoprim or Nitrofurantoin
