LECTURES INFECTIOUS DISEASES AND
VACCINE DEVELOPMENT
LECTURE 1: INTRODUCTION TO INFECTIOUS DISEASES
CONCEPTS AND PRINCIPLES OF INFECTIOUS DISEASES
EXPOSURE
Exposure denotes the risk of, or actual contact with a microbe (the likelihood of host-microbe contact)
INFECTION
Infection is the invasion and multiplication of microorganisms such as bacteria, viruses, and parasites that are
not normally present within the body and the reaction of host tissues to the infectious agents
COLONIZATION AND COMMENSALISM
- Colonization denotes a condition where a microbe that is not causing disease is isolated from a non
sterile site
o Acquired at any point in life, transitory
o Eg meningococci, streptococci, MRSA
- Commensal microbes are usually acquired early in neonatal life. They are not eliminated by the host
response; they are part of the normal flora and are required for normal homeostasis of mucosal and
epithelial surfaces
o Lifelong presence
o Eg staphylococcus epidermidis
LATENCY
The microbe remains present in a host for an undetermined period of time and can lead to host damage
(reaction) that is apparent microbiologically, histopathologically, radiographically, or serologically without
being associated with clinical disease
- Eg HIV, herpes
DISEASE
An outcome of infection where host damage occurs as a result of host microbe interaction and is sufficient to
cause tissue destruction
CARRIER
A carrier is a person who harbours the microorganism and is able to transmit it (during a long period of time)
- E.g. Hep B, Salmonella (Typhoid Mary), MRSA
Marry Mallon (1869 -1938)
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, - Typhoid fever: severe type of salmonella infection
- New York 1906
o 6/11 household members of a rich banker become sick with typhoid fever
o Epidemiological investigation: Irish cook appointed 3 weeks before onset
o More families that reported disease associated with the cook
o Mandatory hospital isolation (2 years)
o Released, but started working under false name
- 1915: typhoid fever outbreak in Sloane Hospital NY
o Isolated during 23 years on North Brother Island
- In total: 50 patients/ 3+
HOST- AGENT INTERACTION
TYPES OF INFECTION
- Whenever we get exposed there are
several options
- Acute infection: for most infections: covid
19: symptomatic or asymptomatic
- Chronic infection: microorganism persist in
the body→ leads to tissue damage
- Latent infection: only reactivates when the
bodies immunity is low
EPIDEMIOLOGICAL TRIAD (TRIA NGLE)
- Agent: microorganisms and their characteristics
- Host: the human who might get infected (risk factors for exposure, susceptibility and response)
- Environment: environmental factors, crowding, sanitation, vectors, access to health services,
ventilation
HOST CHARACTERISTICS
- Exposure: contact patterns, behaviors, hygiene, age and sex
- Susceptibility: age, intact host defense, immune status
- Response: genetic factors, nutritional and immunological status, anatomic structure, presence of co-
morbidities, medication
ON INFECTIOUS AGENTS, INFECTIOUS DISEASES AND HOST RESPONSE
The good: commensal microflora (normal
microflora, indigenous microbiota),
lifelong presence on skin and mucosae
- Opportunistic: infection caused
by another underlying disease
- Autoimmune: infection reacts to
own body
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,The bad: pathogenic micro-organisms
The ugly: pathogenic, causing severe diseases
- Cause disease in previously healthy
- Severe course, high case-fatality rate
- Ebola, Marburg, rabies, tetanus
LOOK AT ANOTHER WAY OF THE TRIANGLE: THE CHAIN OF INFECTION
Find the sources where viruses and bacteria are and eliminate and eradicate them → we want to interrupt the
transmission and protect the host
How successful have we been in eliminating and eradicating?
- Polio 2 and 3: polio 1 is still in some countries, in 2020 Africa free from polio PV1
- Small pox: eradicated in 1980: disease with very obvious skin lesions: you can identify them and
identify the contact of the contacts → easy to eradicate
o Obvious clinical manifestation
o Lifelong immunity and vaccination
o No animal reservoirs
- Measles: has obvious manifestations, life long immunity and vaccination and no animal reservoir → it
is because low vaccine coverage in some parts of the world
- Covid: no obvious clinical manifestations, no lifelong immunity and vaccination, has an animal
reservoir → difficult to eradicate
- Rinderpest eradication: 2011
o 2011 - Global freedom from rinderpest
o The world was officially declared free from rinderpest in 2011 in the course of the 79th OIE
General Session.
o Rinderpest, once the scourge of societies across Asia, Europe and Africa, is only the second
infectious disease, after smallpox for humans, to have been eradicated globally thanks to
decades of internationally concerted effort.
Eradication is worldwide and elimination is from a certain part of the world
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,Modes of transmission
- Direct: touching, inhaling (droplet), sexual contact, blood borne, mother to child
- Indirect: contaminated water, contaminated surfaces, airborne, vectors, vehicles
OCCURRENCE OF DISEASES
MEASURES
Measures that reflect the presence disease in a population
- Frequency of deaths: excess deaths: oversterfte
- Rates that measure the frequency of illness within a specific population
o Incidence
o Prevalence
- Rates that measure the frequency of death within a specific population
o Infection fatality ratio
o Covid= 0.5 – 1% (WHO, aug 2020)
o Case fatality ratio: is higher than infection fatality ratio
Infection fatality rate of covid 19 inferred from seroprevalence data
- 0.00%-1.54%; Large variation depending on many factors: location, population structure, Case mix
infected-deceased, Decline in antibody titers in time, Mortality registries
Case fatality rate
Huge case fatality rate was high in the beginning of the disease: less confirmed cases: only based on what has
been notified: underdiagnosed: population testing→ then the case fatality rate dropped
No one had immunity against covid: so the virus is striking all 7 billion people
Excess mortality
Excess mortality : amount of deaths that are above the threshold
- During winter time it is higher: more viruses circulate
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,Measures of disease frequency
- Incidence measures new cases of disease or health event that develop over a period of time.
- Prevalence measures existing cases of a disease at a particular point in time or over a period of time.
LEVELS OF OCCURRENCE
- Endemic disease (derived from Greek; an demos); a certain disease occurs at a baseline level in the
population (following a certain seasonal pattern) and without new introductions from outside (e.g.
menW before 2015, tetanus)
- Sporadic diseases: cases occur at a low level and irregularly (Zika in the Netherlands)
- Cluster: sudden aggregation of cases, in time and place and with common characteristics (e.g. cluster
of hep A cases in a daycare centre)
- Epidemic disease (epi demos): sudden increase in the number of cases, above what might be normally
expected in the population and during the time frame (e.g. Mpox 2022)
- Pandemic disease (pan demos): epidemic disease spread over many countries/continents (eg
HIV/AIDS, zika, Flu pandemic 2009, COVID-19)
Endemic disease
Why is a disease endemic: when every single case is able to infect another case: one primary case infects one
secondary case
- R0=basic reproduction number
- R0 =1 disease is endemic
- R0< 1 disease will die out (eradication)
- “the average number of secondary infections caused by a single infectious individual during their
entire infectious lifetime, in a susceptible population”
- Primary case (index): R0 = βc D, where
o β = transmission probability
o c = number of contacts
o D = average time spent infectious (= 1/b if the infection rate is b) correctly
- R0→ above 1: disease will become epidemic
Reproduction number (R0) →
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,Vaccination and dansen met jansen, clubs opened for a few weeks in July 2021 → there is a peak in the graph
INFECTIOUS DISEASES SPREAD FOLLOWING CONTACT PATTERNS
- High mobility of populations increase the likelihood and speed of transmission
- Contact patterns
- Mixing patterns between generations/groups
Who infected whom? October 2021 covid 19
TYPES OF EPIDEMICS
- Common source: point source, continuous, intermittent
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, - Propagated
Common source
Propagated epidemic
CONTROL STRATEGIES AND THE ROLE OF IMMUNIZATION
Outbreaks in a historical and global health perspective
HENCE, THE NEED FOR CONTAINMENT MEASURES
- To interrupt further spread of the disease (control) by reducing the number of new cases, the number
of cases currently infected, and decrease morbidity and mortality associated with the disease
- To eliminate the disease from the population (elimination): reduction of the disease incidence to 0 in a
geographical area
- To achieve the complete and permanent worldwide reduction to zero new cases of the disease
through deliberate efforts (eradication)
LESSONS FROM THE PLAQUE
The plaque depopulated towns, turned the country into desert, and made the habitation of men to become
haunts of wild beasts
- Needs a rat to transport the virus who have lice
- They came from Asia
- Quarantine was very efficious
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, - Personal protective equipment to prevent infection
- Also understood that social distancing was important: they let them die and kept away from them:
only way the understood to protect themselves
- Epidemics of plaque in 6th-8th and 14th-17th century
- 2/3 of the population in Europe
Wrap up
- Isolation of the ill
- Personal protection equipment
- Social distancing
- Quarantine of the contacts
- The role of the city administrators
LESSONS FROM THE FLU PANDEMIC
- Seasonal disease now, but has the tendency to occur in pandemics
- Spanisch flu in 1918
- Communicable disease surveillance and response
EBOLA
- The importance of case management
- Contact tracing: case finding: how can you prevent them from infecting others
- Safe and dignified burials
- Social mobilization
Every outbreak has generic control measures to prevent the spread, but also specific measures: depending on
time and geographic
WRAP UP
- Prominent place in history
- Emergence and re-emergence
- Successes
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