Case 16- Virus Flashcards
Main steps of the Virus life cycle
Virus can only replicate inside other living cells.
• Attachment- can have spike proteins which interact with components on the cell
• Entry- can be through phagocytosis
• Replication and protein synthesis- the viral capsule tends to be broken down through an endosome, exposing the viral genome
• Assembly- reform the replicated viral components into a unit
• Release- sometimes destroys the cell
Types of viral transmission
Horizontal transmission- spreads from one person to another person in the same generation, how most viruses are spread.
Vertical transmission- between mother and fetus/baby. How some virus’s are spreed
Zoonotic transmission- not many viruses, the virus is spread from a non human animal to a human often via a biting arthropod vector i.e. an insect
Main types of viral transmission- how the virus gets into the body
Viruses enter humans through the skin or mucous membranes i.e. GI tract or direct inhalation. Can be through damage in the skin. The main routes of transmission are: Respiratory, Faecal-oral. Other types of transmission:
• Sexual= HIV-1, HPV, Herpes simplex virus (HSV), Hepatitis B (HBV)
• Mechanical- Parenteral route, Intravenous drug users and blood transfusion (HBV, HIV-1). Can be through abrasions in the skin (Herpes simplex virus, papillma viruses, some pox viruses). Biting insects
• Urine (rare)
• Via conjunctiva- can gain access to the respiratory tract when you rub your eyes
Examples of respiratory transmisiion
- Rhinovirus (common cold)- most common viral infective agent in humans, about 100 different immunologically distinct types. Adults tend to get it 4-6 times a year
- Influenza (flu)- 20,000 deaths a year in the UK
- Covid-19
- Chicken pox (Varicella Zoster virus) and Smallpox (variola virus)- cause more generalised infection, for example, in the skin
How infectious droplets enter the body in a respiratory infection
1) Inhaled directly into the respiratory tract
2) Enter the conjunctiva and move to the respiratory tract
3) Move from fingers / cold surfaces to the respiratory tract
Faecal-oral transmission
Ingesting food or water that is contaminated with faeal matter. Infections increase with poor sanitation and personal hygiene
Picornaviruses
Non-enveloped virus’s that are spread through the faecal oral route.
• Poliovirus- direct personal contact, sewage contaminated water, very rarely inadequately disinfected swimming pools
• Hepatitis A- sewage contaminated water, vegetables/fruit washed in sewage contaminated water
Polio
Effective vaccination bought down the polio cases. The majority of Polio is asymptomatic but 1:200 will lead to irreversible paralysis. Treated with iron lung. Can cause wasting of limbs and muscle atrophy. Polio remains endemic in three countries: Afghanistan, Nigeria and Pakistan, its on the rise in warzones. Spreads in areas with poor infrastructure and sanitation.
How is norovirus transmitted
Faecal-oral route
1) Contact with infected individual
2) Surface contact- doors, handles, tables
3) Contaminated food/water
4) Aerosols produced from vomit
Viruses that spread through vertical transmission
- Rubella (German measles)- can cause problems with hearing and developmental problems
- HIV- during birth or through breast milk. 15% of children with mothers who have HIV will catch the virus.
Arbovirus
A type of zoonotic virus. It is transmitted via arthropods (they gain entry via the skin). Includes Dengue fever, yellow fever and St Louis encephalitis. Dengue fever is common in the tropics and spread via mosquitos, most will have a mild disease but 10% will develop a severe disease and get haemorrhagic fever.
Zoonotic viruses
Most are Arbovirus, an exception is rabies where the virus spreads from a non-human animal directly via a bite, no vector. Humans are often dead end hosts i.e. it is transmitted no further but in some cases you get human to human transmission
Pathogenicity, Virulence and Pathogenicity factors
Pathogenicity- the severity of the disease caused by different viruses. The more pathogenic a virus the more severe the disease it will cause.
Pathogenicity factors- the characteristics that disease causing viruses possess that allow them to be pathogenic
Virulence- the severity of the disease caused by different strains of the same virus
The Pathogenicity factors of virus’s
- Entry
- Initial replication
- Immune evasion
- Dissemination- spreading
- Further replication
- Shedding- leaves the body in order to infect other hosts
Localized infections
Causes infections at the site of entry or contiguous with, typically epithelia and skin. Won’t have systemic symptoms. Examples; Influenza (Respiratory epithelium), Rhinoviruses (Respiratory epithelium) and Norovirus (GI epithelium).
Generalised infections
Causes infections that spread to target organs or tissues remote from the site of entry. Polio spreads through the faecal-oral route but can cause musculoskeletal issues. Examples- chickenpox, measles, Hepatitis (A,B,C,E) and Rabies
How virus’s spread in a generalised infection
- Initial replication in the respiratory epithelia
- The virus can spread to regional lymph nodes and then enter into the bloodstream (primary viraemia)
- The virus can then spread to other organs like the liver, spleen, bone marrow and blood vessel epithelium. You then get multiplication of the virus at these sites.
- You then get re-entry into the blood stream from these secondary sites (secondary viraemia)
- You may get further multiplication and shedding from the target organ
Incubation period
The time period between viral exposure and onset of illness (symptoms become apparent)
Diseases with different incubation periods
1) Diseases with a short incubation period (<7 days)- typically localised infections, influenza (1-3 days)
2) Diseases with medium incubation periods (7 to 21 days): typically, generalised infection, measles (13-14 days)
3) Long incubation periods (weeks to months)- typically generalised infections. Hepatitis A from sewage contaminated water (3-5 weeks).
4) Very long incubation period (years)- subacute sclerosing panencephalitis (SSPE) measles (rare complication). 2-6 years.
Generation time
The time period between viral exposure and the individual becoming infectious to other.
A lot of diseases spread because the person is infectious before the symptoms even appear
Reproductive number (R0)
The number of subsequent infections in a susceptible population caused by a viral illness in one individual during its infective period. The amount of people the person is likely to spread the disease to. The higher the reproductive number the more infectious a viral disease is.
The generation time and R0 allows predictions on the size and spread of viral disease outbreaks
Acute infections
Normally short lived, self limiting i.e. the flu, common cold and rabies. Tend to be localised in a particular area, no chronic consequences
Subclinical (asymptomatic) infections
No signs or symptoms. For example, Poliovirus (99% of infections are asymptomatic). Still have the potential to spread disease.
Persistent and chronic infections
Acute or subclinical infections that are not terminated by an immune response, 10% of Hepatitis B cases. In hepatitis this can cause scarring of the liver and cirrhosis.
Latent infections
Acute infections followed by a persistent latent infection. The virus becomes dormant within the host cell. Chicken pox can be reactivated and cause shingles in adults. The varicella-zoster virus lies dormant in the ganglia and is then reactivated. Very painful, trigger can be being immunocompromised, stress or sunlight. HSV1 which causes cold sores can go away and then come back. The virus is dormant within the ganglia.
Slowly progressive disease
The virus replicates at a normal rate but the disease takes many years to manifest itself. However, you may be infectious before the symptoms show i.e. HIV-1. Also Prion illnesses (CJD, nvCJD). You may be non-infectious, for example, subacute sclerosing panencephalitis (SSPE) which is a complication of measles. About 1 in 1000 measle cases will develop SSPE and the virus becomes established in the brain it has a 2-6 year incubation period and it can be fatal.
First antiviral drug
Idoxuridine
The 9 diseases that antivirals can be used against
- HIV
- HBV- Hepatitis B
- HCV- Hepatitis C
- HPV- Human papilloma virus
- HSV- Herpes simplex virus
- CMV- Cytomegalovirus
- VZV- Varicella zoster virus
- Influenza
- RSV- Respiratory syncytial virus
The 9 diseases that antivirals can be used against
- HIV
- HBV- Hepatitis B
- HCV- Hepatitis C
- HPV- Human papilloma virus
- HSV- Herpes simplex virus
- CMV- Cytomegalovirus
- VZV- Varicella zoster virus
- Influenza
- RSV- Respiratory syncytial virus
Treatment of acute HCV
Watchful waiting for spontaneous viral clearance. If needed, treatment with interferon starts between 3-6 months to reduce the risk of chronic HCV.
Treatment for chronic HCV
Weekly pegylated interferon-A and daily oral ribavirin
pegylated interferon A:
• It establishes a nonspecific antiviral state in infected cells which inhibits viral replication
• It’s a cytokine.
• Also means the cell is less likely to take up virus’s.
• IFN alpha also enhances the hosts antiviral immune response, possibly speeding the death of cells already infected with the virus.
• Priming the body to have a general antiviral response
Oral ribavirin stops RNA synthesis
Treatment for acute hepatitis B
No specific treatment, you tend to use supportive treatment as well as monitoring to see if it has spontaneously cleared
Treatment for chronic hepatitis
There is a range of oral antiviral agents:
• Tenofovir- inhibits HBV DNA polymerase, cant replicate the genome
• Entecavir- inhibits HBV DNA polymerase
• Pegylated interferon A- antiviral immune response in the body
Treatment for HPV (human papilloma virus)
- Lopinavir- reduces HPV precancerous lesions (trials only)
* Cidofovir- inhibits HPV DNA polymerase (trials only)
HSV treatment
HSV can cause cold sores and genital warts, causes encephalitis. Antivirals:
• Aciclovir
• Valaciclovir
Aciclovir
A type of antiviral
• Inactive in unmodified form, its activated by a viral enzyme- thymidine kinase
• So only active in infected cells, means it has fewer side effects
• The activated drug inhibits viral polymerase, no replication of genome
Valaiciclovir
- Alternative to acyclovir is Valaiclovir, a prodrug of acyclovir.
- It has better oral bioavailability and is converted to acyclovir after absorption in the gut, its more expensive
Treatment for Cytomegalovirus (CMV)
Part of the herpes simplex virus, linked to congenital birth defects. Can be problematic in transplantations. Antivirals:
• Ganciclovir- inhibits viral DNA polymerase. Its much more toxic than acyclovir because its Myelosuppressive, nephrotoxic
Treatment for influenza
Antivirals are given to those in the ‘at risk groups’ which are over 65, pregnant women (or women up to 2 weeks post partum) and a range of other medical conditions. Treatment:
• Oral oseltamivir (Tamiflu)- Neuraminidase inhibitor / prevents newly formed virions from leaving the cell. Neuraminidase is on the outside of the virus and is very important in getting the virus to leave the cell. Can reduce severity and hospital admission
OR
• Zanamivir- trade name is Relenza. Works the same as Tamiflu.
Treatment for RSV
• Ribavirion- no evidence that ribavirion produces clinically relevant benefits in RSV bronchiolitis. Can be used if the patient is very unwell
Causes bronchiolitis in children under 1
Measles
Highly contagious with a R0 number of 18. It is caused by a single stranded RNA morbillivirus in the paramyxovirus family. It is spread via respiratory transmission. A notifiable disease, you must tell the local Health Protection team (HPT). Previously endemic in the UK
Measles vaccination
- Measles vaccine was introduced in 1968- uptake insufficient to cause herd immunity
- MMR vaccine introduced in 1988- coverage with vaccine exceeded 90%, annual notifications fell substantially
- Due to the MMR scandal, there was a reduction in vaccine uptake and cases rose substantially from 2005, however since then it has reduced
Respiratory transmission of measles
- Coughing/sneezing
- Close personal contact
- Direct contact with infected nasal/throat secretions
When can measles be infected from
4 days prior to the onset of rash to 4 days after rash erupts
Timing of clinical features of measles
- Incubation period (10-12 days)- may have no symptoms
- Prodromal phase (2-4 days)- high fever (39-40 degrees), Rhinorrhoea, Cough, Malaise, Mild conjunctivitis, Diarrhoea, Koplik’s spots. Infective from this stage
- Rash (4-10 days)- Morbilliform (measles like), develops over 3-4 days. Covers the forehead, face and neck to trunk. It fades after 3-5 days.
Koplik’s spots
Pathognomic in measles on the buccal mucosa. Small red spots with a bluish white centre
Complications of measles
Complications= 10-20% of cases
• Gastrointestinal- Diarrhoea (8% of cases)
• Susceptibility to opportunistic infections- Otitis media (1 in 12), Pneumonia (1 in 16 most common cause of death)
• Central nervous system complications- Encephalitis (1 in 1000 cases), blindness, Subacute Sclerosing Pancephalitis (SSPE)- rare but fatal
• Death= 1-2 per 100 cases
Who is most at risk of measles complications
- Adults
- Pregnancy- miscarriage, premature birth, intrauterine death, stillbirth
- Immunocompromised- severe and prolonged measles, infections
- Chronically ill or malnourished children- more frequent / severe complications
- Infants- more likely to need hospitalisation than children. Higher risks of complications and mortality
Rubella
Also known as German measles. Spread by respiratory route. Usually a mild disease with a maculopapular rash and lymphadenopathy. Still endemic in many places. Can cause cataracts and dysmorphia of the body
How infectious is rubella
Infectious from 1 week before symptoms to 4 days after rash
Rubella complications
Rarely causes complications in healthy adults. Complications can arise in pregnancy and cause congenital rubella syndrome in the new-born. Before the 12 week gestation period there is a 75% risk of severe malformation, from 13-16 weeks the risk is mainly in sensorineural hearing loss.
Mumps
1) Common worldwide but rarer in the UK
2) Spread through the respiratory system
3) Symptoms- fever, parotosis (swollen glands under the jaw)
How infectious is mumps
Incubation period= 14-21 days
Infectious= from 6 days before parotosis to 4 days after it appears
Complications of mumps
1) Swollen testicles (1 in 4)
2) Viral meningitis (1 in 10)
3) Rare complications- Encephalitis (1 in 1000 fatal)
MMR vaccine
Introduced in the UK in 1988 to replace single vaccines for each disease. The single measles vaccine was introduced in 1968, for Rubella it was 1970
Effectiveness of MMR vaccine and when it is givwn
The MMR vaccine is given at one year and at 3 years and 4 months of age. After two doses of the MMR vaccine:
• About 99 people out of 100 will be protected against measles
• About 88 out of a 100 people will be protected against mumps
• Almost everyone will be protected against rubella
