Population dynamics of infectious diseases Flashcards
List the key pieces of information that are conveyed by the basic reproduction number (R0) of an infectious disease.
Average number of secondary cases generated by a primary case in a totally susceptible population.
- fundamental measure of the transmission potential of a pathogen in a given setting
- determines whether a pathogen can invade
- determines the carrying capacity (proportion immune at equilibrium)
- hence dictates the proportion necessary to vaccinate for eradication.
How can you think of infectious diseases in terms of resource dynamics?
Infectious disease is the product of an ecological interaction between pathogen and host species – host is a resource for pathogen that is exploited by the pathogen
Discuss how different life history strategies of pathogens are reflected in their population dynamics.
Colonisers (eg. HIV) are modelled as SI systems
• SI systems exhibit logistic growth with carrying capacity at 1-1/Ro
• SI systems do not have a tendency to oscillate
• unable to persist in in small,
low-density aggregations of
hosts
• temporary colonisers (eg. gonorhoea) are modelled as SIS systems
• SIS systems have similar behaviour to SI systems
Pathogens conferring lifelong immunity - Invaders - (eg. Measles) are modelled as SIR systems
• SIR dynamics comparable to predator-prey systems
• SIR systems have an inherent tendency to oscillate (regular cycles)
• SIR systems are also subject to fadeouts
• able to persist in in small,
low-density aggregations of
hosts
• antigenically variable pathogens (influenza, malaria) are essentially a set of sequential SIR models – difficult to control through vaccination
Measles life history
Measles – INVADERS - hit&and run
- only lasts ~ 1 week
- short incubation period where viremia is high and individual is infectious but asymptomatic
- fever, rash & other symptoms (you can die during this stage)
- antibodies act against surface antigens, T cell responses, these act to reduce level either completely or to v low levels
- thereafter controlled by natural immune response, which confers LIFELONG IMMUNITY
HIV life history
HIV – COLONISERS - keep host alive as long as possible to keep transmitting, eventual breakdown into (AIDS).
- starts with acute spike in viremia
- rash and flu a bit like measles, viral set point (maintained by combination of cellular and humoral response)
- you can have extended ‘clinical latency’ phase at ‘set point’
- If virus gets through CD4 T cells, drop of T cells causes lack of control of viremia, leading to full blown aids.
Measles virus
The measles virus is a paramyxovirus, genus Morbillivirus.
It is 120–250 nm in diameter, with a core of single-stranded RNA
Two membrane envelope proteins are
important in pathogenesis. They are the F (fusion) protein, which is responsible for fusion of virus and host cell membranes, viral penetration, and hemolysis, and the H
(hemagglutinin) protein, which is responsible for adsorption of virus to cells.
5 stages of an infectious disease
incubation, prodromal, illness, decline, and convalescence periods
Incubation - occurs in an acute disease after the initial entry of the pathogen into the host
- It is during this time the pathogen begins multiplying in the host.
- However, there are insufficient numbers of pathogen particles present to cause signs and symptoms of disease.
How does HIV persist and evade the immune system & maintain chronicity?
- Escape from CD8+ T cell responses – peptides can acquire mutations so no longer recognised by CD8 T cells (??)
- Escape from antibody responses - HIV capable of varying its envelope proteins
- Switch in tropism - HIV able to switch receptor. Allows it to exploit different resource
Malaria
- caused by ?
- symptoms
- what affects disease severity?
Plasmodium spp.
• Apicomplexan protozoa
• Of 156 named Plasmodium species, 4 infect humans (P. vivax, P. falciparum, P. malariae, P. ovale)
• Also sets up chronic infections
• Malaria restricted to areas where environmental conditions allows parasite multiplication in the mosquito vector
Symptoms
• Symptoms include fevers and chills, headache, vomiting, neurological symptoms
Disease severity
• differs acc. to species of Plasmodium, immune status, previous exposure
▪ They use a unique form of actin-based gliding motility to target and invade host cell - this uses highly dynamic actin filaments
Plasmodium (malaria) life cycle
Life cycle
• General plasmodium life cycle: Mosquito infects sporozoites, then liver, merezoites, rbcs, replication, differentiation into gametocytes which are picked up by mosquitos
- Mosquito injects sporozoites into bloodstream when it bites human
- Sporozoites travel to liver and take residence in hepatocytes
- Sporozoites multiply asexually into schizont, which ruptures, releasing merozoites back into the bloodstream
- Merozoites invade erythrocytes, forming ring-like trophozoite.
- The ring stage trophozoites multiplies asexually to form schizonts, which rupture releasing merozoites when rbcs burst
- This cycle of rbc invasion, multiplying and bursting continues, causing malarial symptoms such as chills and sweating
- After several asexual cycles, the merozoites will form gametocytes when it infects a rbc
- Gametocytes sucked up by another mosquito, digesting the gametocytes and allowing them to mature into gametes, which fuse together to form oocyte
- Oocyst develops sporozoites which are released when oocyst ruptures
- Sporozoites migrate to mosquito’s salivary glands
What’s common in Plasmodium and Trypanosoma strategies to evade the immune system?
Both employ antigenic variability strategy
- Both Trypanosoma and Plasmodium have evolved different mechanisms of antigenic variation to evade host immune systems by expressing VSGs (variant surface glycoproteins)
- Able to make new VSGs from library of genes they have which they can swap in and out – great way of achieving promiscuity
- Allows rapid adaptation to changing environments
African trypanosomiasis (sleeping sickness)
- caused by ?
- how do they reproduce?
- symptoms
Trypanosoma brucei
• Free-living (extracellular) parasite carried around in bloodstream of infected hosts
• One of the few pathogens to cross the blood brain barrier
• Carried by Tsetse fly vector between mammal hosts
• Flagellated (9+2)
• Has an unusual organelle called a kinetoplast made up of many copies of the mitochondrial DNA
• Have glycosomes (membrane bound organelles containing the glycolytic enzymes) which are derived from peroxisomes
How do they reproduce?
• In mammal blood & lymph, grow long and thin and multiply by binary fission, penetrate blood vessel endothelium and invade tissue including CNS
• In fly, multiply and enter salivary glands
Symptoms:
- Haemo-lymphatic stage causes fever, headaches, joint pain
- Neurological stage when parasite infects CNS
- Changes of behaviour, confusion, poor coordination
- Usually fatal without treatment
How does Trypanosoma evade the immune system & maintain chronicity?
Trypanosoma
• Have surface glycoprotein – express VSG (variant surface glycoproteins)
• Able to make new VSGs from library of genes they have – great way of achieving promiscuity
How does Plasmodium evade the immune system & maintain chronicity?
Plasmodium
• P. vivax hides in liver
• P. falciparum decorates surface of rbc with antigens (eg. PfEMP1) that are the primary target of antibody mediation
o Allows infected rbc to attach to epithelium
o Stops rbc being trafficked into spleen (where it would be recognised as foreign and destroyed)
o 60 copies of viral gene with it sequentially expresses so that antibodies produced are no longer effective against second variant
o Clonal antigenic variation allows P. falciparum to avoid immune system until it runs out of viral genes or another arm of immune system destroys it
How does TB maintain chronicity?
Hides out in wbcs!!
Mycobacteria are phagocytosed by alveolar macrophages in the lungs and cannot be digested as its cell wall prevents fusion of the phagosome with the lysosome
Able to subvert immune responses and maintain chronic for whole life time
Name infections that can become chronic
AIDS - HIV
Malaria - Plasmodium sp.
Sleeping sickness - Trypanosoma brucei
TB - Mycobacterium tuberculosis
Glandular fever/ mono etc. Herpes virus (eg. EBV)
Chickenpox (varicella) and shingles (herpes zoster) - Varicella-zoster virus
The SI model!!
creating a model to understand colonisation
- describe
- what used for
- equations
Colonisers (eg. HIV) are modelled using SI systems as there is no real recovery term (RIP)
• Split up host pop into 2 compartments. Only 2 possible states
• S = no. susceptible
• I = no. infected
λ = rate of moving S into I = per capita risk of infection
- Assuming S able to move into I at rate λ, this creates a flow from S to I
- Susceptible are being depleted, net loss from this compartment is -λS.
- In I, rate of change is λS
- You can simplify into one equation as S + I = 1 so can use one variable (y=proportion of population infected)
dS/dt = -λS dI/dt = λS
dy/dt = λ(1-y) where λ = By
- SI systems exhibit logistic growth with carrying capacity at 1-1/Ro
- SI systems do not have a tendency to oscillate
How do you understand λ?
λ = By
therefore dy/dt = By(1-y)
λ = rate of moving S into I = per capita risk of infection
The risk of infection depends on the proportion of pop infected
B is a combination of parameters that relate risk of infection to prevalence of infection
A big B can mean lots of things depending on type of pathogen and how it’s transmitted
How do you understand λ?
λ = By
therefore dy/dt = By(1-y)
λ = rate of moving S into I = per capita risk of infection
The risk of infection depends on the proportion of pop infected
B is a combination of parameters that relate risk of infection to prevalence of infection
A big B can mean lots of things depending on type of pathogen and how it’s transmitted
For directly transmitted pathogens
How do you define
B (a combination of parameters that relate risk of infection to prevalence of infection)
B = βN
β = probability of transmission on contact N = population size
therefore λ = βNy
y = proportion of population infected
For sexually transmitted pathogens
How do you define
B (a combination of parameters that relate risk of infection to prevalence of infection)
B = βc
Remember - only 2 people are involved - not a population!!
β = per partner probability of transmission c = average no. partners you have over a period of time
therefore λ = βcy
y = proportion of population infected
How does the SI model behave?
- in the absence of births and deaths
- in what scenarios can a pathogen invade?
dy/dt = By(1-y)
Logistic growth which plateaus where every host is infected - In a realistic scenario you must modify to include births and deaths!!
It’s reasonable to ignore the usual birth/death turnover of the host population if the timescales we’re looking at for the spread of the disease are much shorter than host generation time.
Pathogen cannot invade unless dy/dt>0 when y=0
ie. rate of change of population infected must be >0 when pop is fully susceptible
For this to be true, B/μ>1 because risk and prevalence of infection (B) has got to be bigger than death term (μ) for invasion of pathogen into population to happen (makes sense!!)
R0 = B/μ and is a measure of the average no. secondary cases generated by a primary case in a totally susceptible population eg. R0=3, each primary case individual will infect 3 others
SO in order for a pathogen to invade and cause an outbreak R0 >1
If R0<1, transmission chains are short so epidemic never takes off (either people die so don’t pass on or become immune so can’t be infected again??)
How does the SI model behave?
- with births and deaths
dy/dt = By(1-y) - μy
This is the modified version that includes births and deaths (when pop is stable ie. births = deaths)
o When you start off, slow spread of infection
o Builds up until sufficient no. to keep spreading (exponential)
o Eventually saturates to equilibrium (for each person that dies, a new susceptible becomes infected)
To find out the proportion of people infected at which this equilibrium settles,
Set derivative at dy/dt=0, solve for y, get y=1 - μ/B
This logistic growth is seen in real life! Eg. South Africa HIV
Rate of change in proportion of population infected, TAKING into account host death
dy/dt = By(1-y) - μy
This is the modified version that includes births and deaths
o When you start off, slow spread of infection
o Builds up until sufficient no. to keep spreading (exponential)
o Eventually saturates to equilibrium (for each person that dies, a new susceptible becomes infected)
To find out the proportion of people infected at which this equilibrium settles,
Set derivative at dy/dt=0, solve for y, get y=1 - μ/B
This logistic growth is seen in real life! Eg. South Africa HIV