epidemiology Flashcards
DALYs definition:
the number of healthy years of life lost due to premature death and disability
Yersinia pestis
define R0
R0= “the average number of new cases arising from one infectious case introduced into a population of wholly susceptible individuals” aka basic case reproduction number
define S
susceptible individuals in a population
how do you calculate the true reproductive rate of a disease? or the amount of secondary infections due to case #1.
Effective” R (Re) = R0 x S
how does an epidemic end?
when Re decreases to <1. only when new susceptible are introduced can the Re number go back to >1, causing and epidemic.
How do epidemics continue?
Susceptibles (S–increases):
born
migrate into a population
No immunity (SI model)
Pathogen mutates (e.g. antigenic drift) and can re-infect/or continually infect individuals
Immunity wanes
what causes Epidemic fade-out?
“The elimination of the infectious agent due to chance”
In small populations rather than large populations:
generation (birth) of threshold susceptibles is slow
numbers of infecteds is low
Patterns in epidemic data- what can they tell us?
Infecteds through time: prevalence & incidence
(Retrospective analysis of previous infections)
Origin of the outbreak
Index case – the first case in an outbreak of disease
Mode of spread through the population
Potential incubation period and time of exposure
Clues to identify the infectious agent
(R0 value comparisons)
define incubation period -
the period between infection and clinical onset of the disease
define latent period
the time from infection to infectiousness.
Point Epidemic
Single common exposure and incubation period
Does not spread by host-to-host transmission
E.g. food-borne disease outbreaks
Continuous Common Source Epidemic
Prolonged exposure to source over time
Cases do not all occur within the span of a single incubation period
Curve decay may be sharp or gradual
E.g. water-borne cholera: 1-3 days incubation
Propagated Progressive Source Epidemic
E.g. measles: 10 days incubation
Spread between hosts.
Larger curves until susceptibles are depleted, or intervention is made.
This pattern most likely in a small population.
In a larger population, it would all ‘merge’ together.
endemic vs epidemic
The successive epidemic waves await replenishment of susceptibles.
Host-parasite relationship may eventually dampen down to a stable equilibrium (endemic) state.
Endemic Equilibrium
Stability in the incidence of infection (constant)
Persistence of the parasite in the host population
Each infection produces 1 secondary (new) infection on average, i.e. Effective R (Re) = 1
NB. Re > 1 means epidemic
Re = S x R0
endemicy
Not (overly) common in the developed world.
Exceptions – Chicken pox, influenzas
In the less developed world, more severe diseases are endemic.
Neglected Tropical Diseases (NTDs).
The WHOs 20 priority NTDs, are so because they are endemic in large populations
Endemic diseases are common in animal populations.
Wild – no one is treating
Managed (farmed) – it can be advantageous
what are the determinants of persistence for an endemic?
Critical community size (CCS)
Rate of contact (mixing) for transmission
Duration of infectious period
Survival of host
what is CCS – critical community size
The minimum host population size required for the pathogen to persist’
Of particular concern for microparasites
Macroparasites:
May survive outside of the host
Can/often aggregate – high burdens in a small number of hosts
How does Ebola Virus persist?
1976 Sudan: The first known outbreak killing 151.
1976 Zaire: 280 deaths.
1995 – 2018: Multiple small outbreaks.
2013 – 2016 West Africa: 28616 cases, 11310 deaths.
40% death rate
R0 estimates vary between 1.5 – 2.5
All three countries declared Ebola free by June 2016
what was the death rate and R0 of ebola?
40% death rate
R0 estimates vary between 1.5 – 2.5
All three countries declared Ebola free by June 2016
2014 there was a small outbreak in the Democratic Republic of Congo , explain the cases and why it was seemingly isolated
- 66 cases, and 49 deaths.
Outbreak August 2018 - June 2020, 3481 cases, 2299 deaths (66% mortality)
As well as many other seemingly isolated outbreaks.
How?
It suggests a reservoir host.
what is ebola? and how is it transmitted?
Ebola is a Zoonotic pathogen.
It can be transmitted from animal to human.
Fruit bats being the primary reservoir host.
Fruit bats are not diseased by the Ebola Virus.
There are almost certainly constant human Ebola cases. But these are in isolated communities.
Human to human transmission will drive a large outbreak
How does Phocine distemper (PDV) persist in NW Europe?
1988 & 2002 PDV epidemics in NW European harbour seals harbour and some grey seals.
90% infected
60% rapid mortality
R0 = 2.8
Solid immunity
PDV is not sustained by NW European population
*Seals congregate in discrete patches where direct close contact transmission occurs
*In populations far below the critical community size (CCS) for PDV.
*
* R0= 2.8 requires birth cohort to make up 1/2.8 = 35% of the population size (i.e. the condition where R0 S (Re) >1)
*But seals pup once/yr, max. replacement rate of 20%
*
*Suggests there is a reservoir host
Definition innocuous:
not harmful
give an example of a reservoir host and a carrier
Reservoir host – referring to a population or species
Carrier – referring to an individual
that are infected but have no symptoms but can give to others
eg. STD and Hepatitis B
Typhoid
What is it?
What does it do?
How is it spread?
History?
Control?
macroparasite
infects people and stunts growth and development
spread from person to person or by consumption of food with parasite eggs
-
R0 calculation for macroparasites =
The average number of female offspring produced through the lifespan of one female worm that survive to maturity in the absence of density-dependent constraints on population growth
Summary characteristics of gastrointestinal helminth worms for endemic persistence:*
bHost density (CCS) is not limiting factor to transmission
External “reservoir” of transmission stages
*Long generation time and period of infectiousness
*Immunity is transient
*Continual re-infection
*Mode of transmission: often contaminative – not requiring host to host transmission
aim of the intervention
Control: Maintains the parasite population to an acceptable level
Elimination
Zero incidence in a defined geographical area (local eradication).
Eradication
Zero incidence worldwide
Extinction
Infectious agent no longer exists in nature or in lab.
methods to prevent transmission?
Preventing transmission
Mass (random) or targeted vaccination. e.g. smallpox
by risk group e.g. childhood vaccines MMR
Spatial vaccination, e.g ring vaccination - FMD
Reduction in contact
by handwashing, condom use, environmental sanitation
Intervening after transmission (to prevent further transmission)
Infectiousness curtailment - tracing & isolation, or culling
e.g. SARS, hospital MRSA (humans)
FMD, BSE, avian influenza (animals)
How many (much) should be vaccinated?
R0 < 1
S* = 1 / R0 (Endemic equilibrium)
S = 1- Pc
Pc = immune proportion
1-Pc = 1 / R0
Pc = 1 - 1 / R0
Pc is the (minimum) proportion of individuals you need to vaccinate
how do you control with ought eradication?
e.g. Measles virus (Eliminated locally not eradicated)
Shares some of the properties of smallpox
No animal reservoir
Safe, cheap, effective vaccine available
High disease-related morbidity/mortality therefore high compliance
* But differs from smallpox
Transmitted more readily
R0 substantially higher
Highly infectious though not as virulent
summarise the key points:
Vaccination and Herd Immunity central to Disease Prevention
Age of onset and life span can change R0
R0 = 1 + (L / A)
Following outbreak, identification of 1st and 2nd ring contacts essential for control
Vector-borne infections
Mosquitoes (Anopheles, Aedes, Culex)
Plasmodium spp (malaria),
Filarial worms (filariasis),
Arboviruses (dengue, yellow fever, WNV)
Blackflies (Simulium spp)
Onchocerca volvulus (onchocerciasis)
Tsetse flies (Glossina spp)
Trypanosoma spp (Trypanosomiasis – African Sleeping Sickness)
Triatomine bugs (Triatoma spp)
Trypanosoma cruzi (Chagas disease)
Sandflies (Phlebotomines)
Leishmania spp (Leishmaniasis)
define Anthroponotic + example
:human-arthropod-human - Malaria: p. falciparum MOSQUITOES
define Zoonotic: + example
Animal - arthropod - human → Zoonotic visceral leishmaniasis (ZVL) SANDFLIES
West Nile Virus
A complex host – virus relationship
Birds are primary amplifier hosts
Migratory birds have a role in distribution
Mosquitoes (Culex) vector
How Do You Stop Vectors?
How Do You Stop Vectors?
Vectorial Capacity (C)
“the average number of potentially infective bites that will be delivered by all the vectors feeding upon a single host in 1 day” hence, has units “per day”
R0 = C x d
where d = the duration of host infectiousness (in days)
Vectorial capacity C is particularly sensitive to:
The vector biting rate per day (a2)
The proportion of bloodmeals taken on the host (host choice, h2)
The daily vector survival rate (p)
The latent period of the agent inside the vector (“extrinsic incubation period”) (n = EIP)
examples of vector control
Human bait traps (e.g. Insecticide Treated Net)
Anopheles gambiae (African malaria vector)
Non-human bait traps
Anopheles stephensi (Asian malaria vector)
Urban breeding site source reduction
Aedes aegypti (yellow fever & dengue vector)
Rural drainage of breeding sites
Culex tritaeniorhynchus (Japanese Encephalitis vector)
can global warming have an effect on desees?
yes-> tropical desiese, malaria …
Vectorial Capacity equation
C= ((V/N)(ah)2pn)/-lnp
Number vectors (V)
Number of hosts (N)
The vector biting rate per day (a2)
The proportion of bloodmeals taken on host (h2)
The daily vector survival rate of the vector (p)
Extrinsic incubation period EIP (n)
define EIP: and what does it have to be to be infectious?
Extrinsic incubation period (EIP). e.g. Anopheles gambiae & Malaria
To be infectious = EIP < L (l= lifespan of vector)
Climate may affect whether and for how long
the average vector may be infectious Dv
where Dv = pEIP/(-ln p)
Dv = 0.912 /(-ln 0.9) = 2.7 days
- In hotter climates EIP could reduce to 6 days:
Dv = 0.96 /(-ln 0.9) = 5 days - OR If climate increases survival p to 0.95 / day:
Dv = 0.9512 /(-ln 0.95) = 10.5 days
Thus current vectorial range can be limited if EIP»_space; L
Can climate be used to predict Vectorial Capacity?
Global changes (El Niño and La Niña):
do changes precede epidemics?
yes,
yes
Is EL Nino responsible for periodic epidemic cycles?
Is EL Nino responsible for periodic epidemic cycles?
El Nino of the Southern Oscillation (ENSO)
El Niño surface pressure: high (warm) over W. Pacific (Peru and Ecuador); low over SE Pacific.
Inverse cold phase: La Niña
Strong determinant of inter-annual variation in sea-level pressure across the Pacific Ocean
- “El Niño years” cycle 2-7 years, persisting for 12-18 months
- “El Niño years” Cause weather changes around the world.
what desieses does el nino effect?
Dengue is a mosquito-borne viral infection (Aedes species, primarily Aedes aegypti).
The infection causes flu-like illness, and occasionally develops into a potentially lethal complication called severe dengue (Dengue Haemorrhagic Fever).
Dengue is found in tropical and sub-tropical climates worldwide, mostly in urban and semi-urban areas.
There is no specific treatment for dengue/ severe dengue, but early detection and access to proper medical care lowers fatality rates below 1%.
Dengue prevention and control depends on effective vector control measures.
ENSO statistically associated with malaria outbreaks in Columbia, Guyana, Peru and Venezuela.
ENSO associated flooding enabled epidemics in costal Peru
ENSO associated draughts preceded epidemics in Columbia and Guyana by 12 months
but NOT Brazil and Ecuador.
No clear evidence why ENSO-forecasting is not universal
how severe is Dengue?
Under-reported: Some studies estimate 390 million cases.
Of which 96 million manifest clinically.
About ½ of the world’s population is at risk.
is ENSO forecasting universal?
but NOT Brazil and Ecuador.
No clear evidence why ENSO-forecasting is not universal
what is and how will climate change affect Bluetongue virus (BTV)
Double stranded RNA virus of livestock
Subclinical (normally) chronic infection in cattle = reservoir host
Severe disease in some sheep / deer species
Vector-borne by midges (Diptera: Ceratopogonidae)
Competent vectors traditionally subtropical/ tropical latitudes 350S and 400N
Traditional African/Asian midge vector is Culicoides imicola
BTV midge vector expansion in Europe
Temperature
Warm/hot periods in autumn/summer increases transmission potential
Warm nights/winter increases virus persistence to “overwinter”**
Induces competence of traditionally non-vectorial European midges
Precipitation
Governs size / persistence of semi-aquatic breeding sites
Moisture governs key microhabitats for adults
e.g. C. imicola breeds in wet organic-matter rich soil, but pupae do not survive flooding
–> Temperature rises increase competence of traditionally non-vectorial species; variable for C. obsoletus in the UK
species of coronavirus
*Infection – SARS-COV 2
One of six species of coronavirus known to infect humans.
*SARS-CoV and SARS-CoV-2 are the same species, different strains.
*There is MERS.
*The other 4 cause the common-cold.
*Disease – COVID-19
Why do the virus and the disease have different names?
Origin of SARS-CoV-2
Wet-market in Wuhan, China, December 2019.
Infection occurred due to a ‘spillover’ event. Reservoir host. Bats and maybe…
Natural habitat encroachment, parallels with other SARS and MERS, influenzas and Ebola.
Zoonosis (plural Zoonoses)
The movement of people (behaviour) is key to the transmission dynamics.
what is Co-morbidity and did it effect people with covid?
The two infants had severe co-morbidities.
Age structured co-morbidity data is unavailable/well-hidden.
Increased risk of death with co-morbidities is known/quantified
Of the 33,841 deaths that occurred in March and April 2020 involving COVID-19 in England and Wales, 30,577 (90.4%) had a co-morbidity (ONS).
list and explain the Disease states for covid
No clinical disease (asymptomatic)
Pneumonia/Viral disease
Autoimmune (developing after viral disease)
Deaths by each disease…
‘Long COVID’
incubation and latency meaning and application to covid
incubation period - the period between infection and clinical onset of the disease
latent period - the time from infection to infectiousness.
Often the same.
SARS-CoV-2 has an asymptomatic infectious state.
Latency can be shorter than the incubation (always considering averages with these values, but there is a lot of heterogeneity).
Asymptomatic transmission makes surveillance and intervention more difficult.
R0 for corona virus
- 1.4 and 2.5 on 23.01.2020
- another study between 2.24 to 3.58.
Multiple studies estimated a R0 between 2 and 4.
the R0 for the 2009 flu ‘pandemic’ was 1.5 and for 2002-2004 SARS outbreak (a coronavirus) it was 3.0.
control of covid and Pc number
Distancing, ‘lockdowns’, quarantining – a reduction in contact rate.
Scientifically simple
Socially and politically complicated
Face coverings directly affecting the probability of transmission.
A ‘lockdown’ and face coverings both reduce ‘effective contacts’
Vaccination – a reduction in Susceptibles
Pc = 1 - 1 / R0
Given R0 = 3 – 4, Pc =67% - 75%
explain why immunity is complicated for covid
Other coronaviruses confer no lasting immunity.
Immunity is now a complicated picture for SARS-CoV-2
What is waning immunity?
What does it represent?
A reduction in the host’s immune response OR
A specificity of immune response that does not respond to a mutated/different strain
For the sake of the epidemiology, it doesn’t matter which.
Important for long term Public Health strategy and planning
vaccination of covid
Administering a vaccine is a vaccination.
Raising an immune response is immunisation.
Vaccine efficacy is what percentage of those vaccinated, are immunised.
Regulators were prepared to accept a vaccine of 50%.
November – December 2020 brought vaccines achieving 90-95%.
Pc = 1 – 1/R0
Take R0 = 4, Pc = 0.75.
But only 90% of those vaccinated raise an immune response.
0.75 x 0.9 = 0.675. i.e. 67.5%.
If only 75% are vaccinated, herd immunity cannot be reached.
Pc = (1-1/4)/0.9 = 83.3%
Of course if R0 =3, and efficacy = 95%, then Pc = 70%.
function of the covid vaccine
Prevent disease – lowering morbidity and mortality in those vaccinated
Prevent infection transmission - protecting those vaccinated, AND indirectly protecting those not vaccinated due to reduced transmission
Prevention of disease means that infection can still circulate.
We have a vaccine against COVID-19, not SARS-CoV-2
It protects against (severe) disease.
Therefore the virus circulates, and the unvaccinated can become diseased
the health of the public
Incorporation of multiple factors. Who has poor health? How effective is prevention? How much does prevention cost? How much does disease cost (human cost and financial cost)?
Public Health policy should be made based on the answer to these questions and more.
UK - Public Health England/Wales/Scotland/Northern Ireland
National Institute for Health and Care Excellence (Nice)
Joint Committee on Vaccination and Immunisation (JCVI)
Policy – which isn’t necessarily made the Scientists
