Transmission of infectious disease Flashcards
Which three groups of factors are important in pathogen transmission?
- Donor factors
- Host & pathogen interface interactions
- Recipient factors
What are the modes of respiratory virus transmission? (3)
- Indirect contact -> transmission via fomites
- Large droplets (>5 µm) which can land on mucosal surfaces of people in close proximity
- Aerosols (<5 µm), which are inhaled and deposited in respiratory tracts
What is the major difference between large droplets and aerosols?
The time they can be airborne, and as a result of that: the distance they can travel
Which are the forces acting on particles in an aerosol? (3)
- Gravity -> becomes smaller as particle becomes smaller
- Diffusion forces
- Drag forces
Particles in an aerosol originating from the URT are [larger/smaller] than particles originating from the LRT
Larger (so: the deeper the particle is formed, the smaller it is)
The [larger/smaller] a droplet is, the deeper it travels into the respiratory tract of the person inhaling them
Smaller
Which donor factors are needed for efficient respiratory transmission? (5)
High infectious load ->
1. High viral load
2. Replication in URT
3. Induction of mucous production
4. Induction of clinical signs such as coughing or sneezing
5. Host immune responses
Which factors influence the stability of particles/respiratory viruses while airborne? (5)
- Enveloped/non-enveloped virus
- Temperature
- Relative humidity
- Ventilation/air movement
- UV radiation
Which recipient factors influence respiratory virus transmission? (4)
- Infectious dose received
- Size of virus-containing aerosols
- Tissue/cellular tropism
- Host immune responses
Which animals are commonly used to study respiratory transmission of influenza A?
Ferrets
What makes ferrets a good model system for respiratory transmission of influenza A? (4)
- Susceptible to natural infection
- Respiratory disease & lung pathology similar to humans
- Patterns of virus attachment similar to humans
- Useful for airborne transmission
What are the differences between avian flu and human flu when it comes to:
1. Organ targeted
2. Receptor
3. Receptor location in humans
4. Temperature
- Avian flu targets the intestinal tract, while human flu targets the upper airways
- Neu5Ac-α2,3-Gal for avian flu, Neu5Ac-α2,6-Gal for human flu
- Neu5Ac-α2,3-Gal is located in the LRT in humans, while Neu5Ac-α2,6-Gal is located in the URT
- Avian flu is optimal at 41 °C, while human flu is optimal at 33 °C
Why does avian flu cause lower respiratory symptoms in humans?
Its entry receptor (Neu5Ac-α2,3-Gal) is located in the LRT of humans
Why does human flu cause upper respiratory infection in humans?
Its entry receptor (Neu5Ac-α2,6,Gal) is located in the URT of humans
Why is it beneficial to human flu that its optimal temperature is 33 °C?
This is the approximate temperature of inhaled air
Which sources/experiments can be used to obtain information about the shedding of respiratory viruses? (5)
- Outbreak reports
- Experimental infection of humans
- Animal models
- Data on exhaled breath
- In vitro experiments such as artificial aerosolization & collection
What are three common ways of faecal-oral transmission?
- Contamination of the environment
- Contamination of fomites
- ‘Fingers to food’
Under which conditions do large outbreaks of faecal-oral transmitted pathogens often occur?
When a pathogen gets incorporated during processing of food
What is the difference to ‘small’ food handlers and large food producers when it comes to faecal-oral transmission?
Small food handlers often cause local, endemic outbreaks, whereas large food producers ship their foods (and possible pathogens) worldwide
What are donor factors that can influence faecal-oral transmission? (5)
- Shedding in stool
- Pathogen stability
- Intestinal niche adaptation of pathogen
- Pathogenicity (=ability to cause diarrhoea) of pathogen
- Gut microbiome of host
The gut microbiome of the host has most effect on feacal-oral transmission of [viruses/bacteria]
Bacteria
What are host-pathogen interface interactions that influence faecal-oral transmission? (4)
- Environmental microbiome
- Environment (climate, UV-radiation)
- Stability of pathogen in the environment
- Human behaviour
What kind of climate is generally more stable for transmission of pathogens? Why?
Cool climate -> pathogens are generally more stable at lower temperatures
Which human behavioural factors are important for host-pathogen interface interactions? (3)
- Hygiene
- Agriculture
- Food preference
What are recipient factors that are important for faecal-oral transmission? (4)
- Microbiome of recipient
- Receptor expression in intestinal tract
- Stability of pathogen in new host
- Intestinal tract niche adaptation of pathogen
What are common characteristics of viruses that transmit via the faecal-oral route? (4)
- Viruses shed via the stool
- Clinical symptoms increase likelihood of faecal-oral transmission (vomiting, diarrhoea)
- Viruses have to be stable in the environment
- Viruses have to adapt to (harsh) conditions in the intestinal tract
True or false: for viruses to be shed via the stool, they need to be produced in the intestinal tract
False; viruses that replicate elsewhere can also move to the intestine after replication and end up in the stool
Which factors in the mouth make it hard for pathogens to survive or attach there? (3)
- Flow of liquids, preventing attachment
- Proteins in saliva (lysozyme, etc.)
- Presence of normal flora
What is the effect of stomach acid on pathogens?
Inactivation/killing of acid liable bacteria/viruses
Which factors in the duodenum can kill viruses?
Bile salts -> can destroy lipid envelopes of many viruses
Why is the presence of bile salts sometimes beneficial for pathogens?
Some gastrointestinal viruses require presence of bile salts to get internalized in intestinal cells
Which factors in the intestine are important to prevent infection? (6)
- Peristalsis -> prevents microorganisms
- Flow of liquids
- Shedding of epithelium, hindering establishment of pathogens
- Mucus -> hinders binding of microorganisms
- Antiviral defences such as proteolytic enzymes & IgA
- M-cells sample intestines and activate adaptive immunity if necessary
Which factors in the colon prevent infection? (3)
- Normal flora
- Peristalsis
- Shedding of epithelium
Why is the majority of gastro-intestinal viruses ‘naked’?
These viruses lack a lipid envelope, causing them to be more stable in the harsh environment of the gastrointestinal tract
What model systems are available to study faecal-oral transmission? (3)
- Cell culture models
- Animal models
- Mechanical models
Why are cel culture systems for enteric viruses difficult to find?
Many viruses that replicate in the intestinal tract don’t replicate in cell culture
What are the structural characteristics of norovirus?
RNA capsid virus, no envelope
The infectious dose required to establish a norovirus infection is [high/low]
Low
Which factors make norovirus a very infectious gastro-intestinal virus? (4)
- Faecal shedding in extremely high levels
- Low infectious dose
- Stable outside host
- Can cause asymptomatic infections
Why is norovirus unable to infect B-cells on its own, but is able to do so in the presence of bacteria?
LPS on bacteria can stabilize virus particles, allowing them to cause infection
What are donor factors that influence the transmission of HIV? (3)
- High viral load
- Virus tropism
- Transmission fitness of virus
Which factors determine the viral load in HIV-infected individuals? (2)
- Stage of infection
- Use of PrEP/PEP/cART
Which sexual intercourse factors influence HIV transmission?
- Condom use
- Type of sexual intercourse
Which recipient factors influence the transmission of HIV? (5)
- Use of PrEP/PEP
- Virus tropism
- Presence of STDs -> increase chance
- Biologial sex -> females more at risk
- Presence of foreskin
Which three stages does HIV-infection have?
- Acute infection
- Chronic infection
- AIDS
How long does the acute stage of HIV-infection last?
10-16 weeks
What symptoms are characteristic of acute HIV infection? (5)
Flu-like symptoms, such as:
1. Headache
2. Fever
3. Lymphadenopathy
4. Malaise
5. Rash
Why can’t HIV be diagnosed based on symptoms? (2)
- Only ~50% of infected individuals experience symptoms
- Symptoms are aspecific
How long does the chronic stage of HIV-infection last (on average) before AIDS occurs?
~8 years
What symptoms can be present during acute HIV-infection?
Fatigue & lymphadenopathy (present in minority of patients during minority of time)
What is AIDS?
Occurence of opportunistic infections due to increasing immune system dysfunction
Which symptoms may occur during AIDS, in addition to infections? (2)
- Weight loss/wasting
- Dementia
True or false: individuals with AIDS can have their life expectancy fully restored when they receive treatment
False; when a person reaches AIDS, their life expectancy is reduced, even if CD4-count is restored using treatment
Which stage of HIV-infection is key for prevention?
Acute stage -> low symptoms & high viral load = high transmission
Which type of sexual activity has lowest chances of transmission of HIV?
Heterosexual transmission
Why is the chance of transmission of HIV higher in MSM?
Anal sexual intercourse leads to small abrasions, allowing for easy infection
Which event has the highest transmission chance for HIV?
Blood transfusion
HIV requires a [high/low] infectious dose to establish infection
Low -> max. 2 virus copies establish an infection
How can it be established that max. 2 virus copies establish HIV infection?
Low genetic variation of viruses in a single patients points to a (very) low number of original viruses
How can the low risk per sexual act of HIV be explained?
Low amount of virus particles causing infection can explain the low chance
What is a bottleneck event? Why is it relevant in the context of the transmission of HIV?
A reduction of genetic diversity in a population -> because only 1/2 viruses establish infection in a new host, genetic diversity in the new host is drastically reduced when compared to the original host
What is a quasi-species?
Cloud of genetically different viruses
What is Fiebig staging?
Clinical classification of acute HIV infection based on an ordered appearance of particular events
Which two factors are the main reasons for the high infectiousness of acute HIV?
- High viral load
- Viruses in the acute stage infected somebody recently -> still have high transmission fitness
Why do viruses in chronic HIV lose (part of) their transmission fitness?
Adaption to host causes lower efficiency in infecting new individuals
How does HIV disseminate after infection? (2)
- Local stage -> exponential growth
- Dissemination & establishment in lymhoid tissues
Why is the local stage of HIV a window of opportunity?
The virus stays local for 2-5 days and can still be exterminated using PEP
How quickly after infection should PEP be started?
Within 72 hours of infection
Why is PEP effective? (2)
- Small founder population due to low number of HIV-copies establishing infection
- Local infection stage that can be countered
