Lectures nutrition and infectious disease
Lecture 1: Nutrition and infectious diseases in the context of Health Sciences
Marinka van der Hoeven:
Content:
Focus on the use of epidemiology in research related to nutrition and infectious diseases
Differences and similarities between the three different groups of pathogens (bacteria, viruses and
parasites)
Measurements of infectious disease, nutritional status, dietary intake
Issues related to studies that include nutritional exposure and outcome
Objectives:
Employ epidemiological methods to describe and understand risk factors
Employ epidemiological and biological methods to develop an appropriate study design
Provide critical analysis of public health policies, scientific articles and intervention protocols related
to infectious diseases
Discuss the principles of infectious disease in the context of global public health concerns
Infectious diseases:
Infection: The presence of a (micro-) organism that is able to divide/reproduce
Illness: The moment at which the (micro-) organism causes (tissue) damage (that might express itself
in symptoms)
Pathogen: A (micro-)organism that is able to cause illness
- We also have organisms in our body and they are able to divide and reproduce but they do not cause
illness. Our gut bacteria are not causing any illness so it is not a pathogen.
- It is important to know the lifecycle to improve the health of the host or to
eliminate the pathogen
Classification of infectious pathogens:
The classification is based on their size.
On top you see the worms, the tapeworm can reach one meter length and is
visible with the naked eye. Then you have the protozoa and the bacteria you can
only see with a light microscope. Then you have the viruses you can only see with
an electron microscope.
The difference between Infection versus illness:
Example tuberculosis
Mycobacterium tuberculosis
90% asymptomatic (no illness)
Can be reactivated after years
Immune deficiency (e.g. AIDS) can reactivate tuberculosis to cause
disease/illness
Example of tuberculosis: It is a bacteria that causes the infection, but 90% have no
signs of illness, they are asymptomatic. They are infected but the bacteria does not
cause damage to the body and there is no illness. Illness starts when tissue damage
occurs. A bacteria can cause damage without the host noticing.
Infection:
You see the tip of the iceberg but not what is beneath the see. We see the disease
picture (tip), but we also see people with an asymptomatic infection, they are
infected but might not have symptoms (beneath).
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,Child under-nutrition and immune functioning:
Important picture from the paper Ibrahim
Nutrition in relation to the functioning of the immune system: It shows that nutrition deficiencies, for
example iron or vitamin A deficiency might result in:
- a reduced intestinal barrier function.
- Gut inflammation – altered immune homeostasis
- intestinal disbalance of the gut microbiome (intestinal dysbiosis).
For example, vitamin A does not only play a role for your sigh but also for mucous membranes. This
membrane might be damaged which results in gut inflammation and it reduces its main function as a
barrier and altered immune homeostasis and intestinal disbalance of the gut microbiome (intestinal
dysbiosis). But this is not only the case for nutrient deficiencies, but also for environmental insults and
enteric infection.
Immune deficiency/ impaired host defence/metabolic cost: It
also works the other way around.
- Systemic inflammation
- Microbial translocation
- Altered innate immune function
Might lead to Immune deficiency/ impaired host
defence/metabolic cost
Therefore, it is important to take nutritional status into account.
Interplay of malnutrition with environmental enteric dysfunction and systemic inflammation. Exposure to
intestinal pathogens and intestinal dysbiosis, as a consequence of poor sanitation and possibly specific
nutrient deficiencies (e.g., zinc, vitamin A, and protein), lead to intestinal inflammation and disruption of
intestinal barrier function. Impaired barrier function allows the translocation of bacteria and bacterial
products from the intestine, which activate innate immune cells in the mesenteric lymph nodes, liver, and
systemic circulation to generate proinflammatory cytokines. The increased systemic inflammation carries a
metabolic cost and leads to impaired host defense. Collectively, these vicious cycles lead to growth
faltering and increased mortality.
Infection -> undernutrition:
Plasmoudium and hookworm -> Anemia.
Ancylostoma duodenale
Male worm 8-10mm, female worm 10-13mm
Large bucal cavity with cutting teeth
Life span 1 year, sometimes longer
Another example of how infection influences nutritional status: Plasmodium, hookworm.
- Plasmodium causes malaria which could lead to anemia. A hookwork infection could also lead to
anemia.
- The male becomes smaller than the female worm. They have cutting teeth with which they attach to
the wall of the intestine. They have a lifespan of a year
Hookworm lifecycle:
Ancylostoma duodenale/Necator americanus
Within 1-2 days larvae develop (under warm, humid conditions)
Larvae grow in/on feaces or on soil
After 5-10 days development of infectious larvae (can migrate and
survive for weeks)
Migration via vascular system, lungs, trachea to intestine
24 hours after infection in intestine larvae attach and develop into
adult worms
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, If orally infected by A. duodenale no lung passage
It shows the full lifecycle of this pathogen, the hookworm.
The larva develops form eggs in human feces. This larva penetrates the skin when people walk barefoot
for example. The larva migrates in the vascular system to the lungs where they are cuffed up, they cause
irritation. The larva come back in the trachea and are swallowed in the intestine. 24 hours after the
infection in the intestine, they develop into adult worms. If you want to intervene and prevent infection,
you need to know how infection takes place.
What symptoms do you think people might notice if the host is getting infected with this hookworm?
Ancylostoma duodenale/Necator americanus
Symptoms
Local skin manifestation: “Ground itch” during penetration of the larvae
Airways: During lung migration: coughing, sputum, fever
Intestine: Abdominal pain, diarrhea, weight loss, and tiredness
Nutrition and hookworm infection:
Iron deficiency anemia
Caused by attachment, blood loss, secretion of anti-coagulants
Protein energy malnutrition
Caused by vomiting, reduced food intake, diarrhea
- Iron deficiency anemia is caused by attachment of the hookworm to the walls of the
intestine: it causes damage there. There could be blood loss of the attachment which could lead to
tiredness. The intestine is sometimes less able to take up nutrients.
- If a person is already malnourished or on the borderline then this might be the point to tip someone
over and increases the risk for a low nutritional status.
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,Suzanne Smit:
Lecture based on the literature, chapter 6 Rothman.
Objectives:
History of infectious disease epidemiology
Differences infectious disease and non-infectious disease epidemiology
Transmission
Basic reproductive number
Effective reproductive number
Herd immunity
Vaccination coverage
The Reed-Frost epidemic model
Infectious disease epidemiologic investigations
Epidemiological study design (available on Canvas)
(History)
Special features infectious disease epidemiology:
Can you think of why infectious disease epidemiology is different from non-infectious disease
epidemiology?
Can everyone spread the disease? Asymptomatic and immune people play a big role in transmission (In
infectious diseases non-symptomatic people can still spread the disease). Asymptomatic people can be
people that can still transmit and immune people have a protective effect for the population ass well.
1. A case may also be a risk factor
Transmission of disease between cases
Contact patterns in society important
A case of diabetes: There would be no risk factor for anyone. If I would have
influenza, I could be a risk factor to spread it to others.
Cases
Index – the first case identified
Primary – the case that brings the infection into a population
Secondary – infected by a primary case
Tertiary – infected by a secondary case
If a person who is infected by the primary, it is the first case identified, the index.
People may be immune
Many infectious diseases (or their vaccines) confer (life) long immunity
3. A case may be a source without being recognized as a case
Asymptomatic or subclinical infections play an important role
Basic reproductive number:
Potential for an infectious disease to spread:
Probability of transmission
Frequency of contacts
Duration of infectious period
Immunity in the population
If the infectious period is longer it raises the likelihood of transmission
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,Basic reproductive number R0= Average number of infections that would be caused by one
infectious person when everyone is susceptible
The basic reproductive number of the figure would be two. The primary case spreads the
infection to 2 other people.
Formula basic reproductive number:
R0 = β * c * D
β: measure of infectiousness
c: number of contacts per infectious person per day
D: number of days of infectiousness
Measles have a basic reproductive number of around 15.
The droplets are in the air for quite a long time. HIV has a
lower R0. It has a different, specific transmission. for Ebola,
people are infectious only when symptoms occur.
Just keep in mind, the infectiousness, number of contacts
and the duration of infectiousness
What is the difference between the basic and effective
reproductive number?
It is based on the basic, but something is added to the
equation. Some people are immune.
Effective reproductive number Rt= Average number of
infections resulting from one infectious person given that not everyone is susceptible
Formula effective reproductive number:
Rt = β * c * D * S
β: measure of infectiousness
c: number of contacts per infectious person per day
D: number of days of infectiousness
S: fraction of the host population that is susceptible
We add the fraction of the host population that is susceptible. If we have a fully susceptible population
the number would be 1 and we would just have the basic reproductive number. If we have people who
are immune, this becomes a fraction and is added to the equation/formula.
Endemic state is when the effective reproductive number equals 1 then there is transmission, but the
number of cases remains constant.
Epidemic: the effective reproductive number is greater than 1. We have an increasing number of cases.
A global epidemic is what we call a pandemic
Our strategy to get rid of this pandemic in terms of effective reproductive number is to lower the Rt below
1. when we want to lower the Rt below the 1. Every person spreads it to less than 1 person down the line,
the infectious disease dies out.
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,Potential interventions:
Rt = β * c * D * S
β: measure of infectiousness
c: number of contacts per infectious person per day
-> social distancing
D: number of days of infectiousness
-> treatment
S: fraction of the host population that is susceptible
-> herd immunity (+ by vaccinating, we can lower the fraction of the host population that is susceptible)
For corona the Rt was estimated to be 4-5. After the lockdown we decreased the effective reproductive
number below 1.
Herd immunity= The number of immune people in the population decreases
the risk of infection to the susceptible population by reducing the probability of
exposure
How does herd immunity work?
When 0% is vaccinated, the infectious disease spreads rapidly. The more people
who are vaccinated or are immune, the less the infectious disease can spread.
- We have a population with 4 generations, all are susceptible. The R0 for the first generation is 3.
- When 1/3 is immune. Can the people behind the immune ones still get the disease? The red after the
black are indirectly protected. People are indirectly protected by the immune people around them
Example:
- Virus
- R0=6
- Proportion of people
protected if:
o 1/3 is immune
o 3 generations
What is the proportion of
people that is protected if
1/3 is immune and we have 3 generations?
Each person infects 6 others. We have 3 generations so in total 43
people. 1/3 of 43 is 14 people who are immune.
First generation: 1 person
Second generation: 6 persons of which 1/3 is immune=6: 3= 2 immune
Third generation: 36 persons of which 1/3 immune= 36: 3- 12 immune
22 people are protected of 43 people in total= 51%
If there are people that are immune in the population, susceptible people are also protected by immune
people in the population, because these immune people won’t spread it to others.
Everything about this lecture and the herd immunity is important for the exam.
Herd Immunity Threshold:
Percentage immune individuals providing sufficient herd immunity to stop the outbreak
Formula proportion to be immunized: Rt<1 when proportion immunized > 1-1/R0 (when
vaccine efficacy 100%)
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, Depends on:
Risk of transmission per contact – probability of transmission
Frequency of contacts
Duration of infectious period
Immunity of the population – e.g. natural immunity, vaccination coverage and
vaccine efficacy.
We want to decrease the Rt below 1, because then it spreads to less than 1 person down the line. How
many people do we need to immunize to provide sufficient immunity to stop an outbreak (to get an Rt
below 1)? We need a proportion of greater than 1-1/R0.
Example:
- Virus
- R0=6
- Vaccine efficacy 100%
- How many people should you vaccinate for Rt <1
o 3 generations
You can visualize it or use the formula.
Formula: 1: 6= 0,167
1-0,167= 0,83 x 100= 83%
Greater than 83% should be vaccinated to have Rt below 1
83% of 43 (see previous drawing for total) = 35,69
More than 36 people should be vaccinated to have Rt below 1
It depends on the R0, the basic reproductive number.
You can also visualize this:
Rt below 1 is that you want the disease to spread from 1 person to
less than 1 person below the line. Here, you can also see that when
you want to reach a Rt of 1, you have to reach a number of 5/6 of the
population is immunized or indirectly protected, only than the
epidemic will die out (Rt <1)
100: 6 x 5= 83,3
(In chapter 6 the vaccination coverage is covered in the formula. It can be included)
Herd immunity:
The number of immune people in the population decreases the risk of infection to the susceptible
population by reducing the probability of exposure
The higher the basic reproductive number of infection, the larger is the number of immune people
required to confer herd immunity: In terms of measles, with a high R0, we need a larger amount of
people immunized compared to something which has a lower R0 such as Ebola.
Exercise:
What happens with a measles ‘outbreak’ under the following vaccination coverages:
• 50% (example Urk region)
• 90% (average Dutch vaccination coverage)
• 98% (highest vaccination coverage found in Dutch region)
With a coverage of 50%, many susceptible people are around, measles spread easily. The higher the
vaccination coverage, the less people get infected
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