Infectious Dose
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The concept of a minimal infective dose (MID), also known as the infectious dose, has traditionally been used for infectious
microorganisms A microorganism, or microbe, is an organism of microscopic size, which may exist in its single-celled form or as a colony of cells. The possible existence of unseen microbial life was suspected from antiquity, with an early attestation in ...
that contaminate foods. MID was defined as the number of microorganisms ingested (the dose) from which a
pathology Pathology is the study of disease. The word ''pathology'' also refers to the study of disease in general, incorporating a wide range of biology research fields and medical practices. However, when used in the context of modern medical treatme ...
is observed in the consumer. For example, to cause gastrointestinal disorders, the food must contain more than 100,000 ''
Salmonella ''Salmonella'' is a genus of bacillus (shape), rod-shaped, (bacillus) Gram-negative bacteria of the family Enterobacteriaceae. The two known species of ''Salmonella'' are ''Salmonella enterica'' and ''Salmonella bongori''. ''S. enterica'' ...
'' per gram or 1000 per gram for
salmonellosis Salmonellosis is a symptomatic infection caused by bacteria of the ''Salmonella'' type. It is the most common disease to be known as food poisoning (though the name refers to food-borne illness in general). These are defined as diseases, usuall ...
. however, some viruses like DHBV( duck hepatitis B virus) need as low as 9.5 x 10(9) virus per milliliters to cause liver infections.To know the dose ingested, it is also necessary to know the mass of the portion. This may be calculated using the following formula: :d\ =\ c \times m where: *d = number of bacteria i.e. dose *c =
concentration In chemistry, concentration is the abundance of a constituent divided by the total volume of a mixture. Several types of mathematical description can be distinguished: '' mass concentration'', '' molar concentration'', '' number concentration'', ...
of bacteria *m = mass This formulation has served as a basis for reasoning to establish the maximum concentrations permitted by the microbiological regulatory criteria intended to protect the health of consumers.


Dose–effect and dose–response relationship

The concept of a
dose–response relationship The dose–response relationship, or exposure–response relationship, describes the magnitude of the Stimulus–response model, response of an organism, as a Function (mathematics), function of exposure (or Dose (biochemistry), doses) to a Sti ...
dates back to as 1493 but its modern usage reaches to the 20th century, as quantitative risk assessment matured as a discipline within the field of food safety. An infectious bacterium in a food can cause various effects, such as
diarrhea Diarrhea (American English), also spelled diarrhoea or diarrhœa (British English), is the condition of having at least three loose, liquid, or watery bowel movements in a day. It often lasts for a few days and can result in dehydration d ...
,
vomiting Vomiting (also known as emesis, puking and throwing up) is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenteritis, pre ...
,
sepsis Sepsis is a potentially life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage of sepsis is followed by suppression of the immune system. Common signs and s ...
,
meningitis Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord, collectively called the meninges. The most common symptoms are fever, intense headache, vomiting and neck stiffness and occasion ...
,
Guillain–Barré syndrome Guillain–Barré syndrome (GBS) is a rapid-onset Paralysis, muscle weakness caused by the immune system damaging the peripheral nervous system. Typically, both sides of the body are involved, and the initial symptoms are changes in sensation ...
, and death. Most of the times, as the dose increases, the severity of the pathological effects increases, and a "dose–effect relationship" can often be established. For example, the higher the dose of ''Salmonella'', the more diarrhea occurs soon after ingestion until it reaches to its maximum. However, among people who have ingested the same dose, not all are affected. The proportion of people affected is called the response. The dose–response relationship for a given effect (e.g., diarrhea) is therefore the relationship between the dose and the likelihood of experiencing this effect. When the response is less than about 10%, it is observed that there is a strictly proportional relationship between dose and response: :P \propto r \times d where: *P = probability of the effect considered *r = response *d = dosage The dose-effect relationship and the dose-response relationship should not be confused.


Consequences

The existence of this relation has a first important consequence: the proportionality factor, symbolized by the letter r, corresponds precisely to the probability of the effect considered when the dose is equal to one bacterial cell. As a result, the minimum infective dose is exactly equal to one bacterial cell, deviating from the traditional notion of the MID. Proportionality has a second consequence: when the dose is divided by ten, the
probability Probability is a branch of mathematics and statistics concerning events and numerical descriptions of how likely they are to occur. The probability of an event is a number between 0 and 1; the larger the probability, the more likely an e ...
of observing the effect is also divided by ten. Additionally, it is a relationship without threshold. In industrial practice, everything is done to reduce the probability that a serving contains the bacterium. There is therefore on the market food in which, for example, only one serving in a hundred is contaminated. The probability of the effect considered is then r / 100. If one in ten thousand is contaminated, the probability goes to r / 10,000, and so on. The line representing the relation can be extended towards zero: there is no threshold. If the probability of not being infected when exposed to one bacterium is 1-r then the probability of not being infected by bacteria would be (1-r)^n\approx\exp(-nr), so the probability of being infected is 1-\exp(-nr). For readers familiar with the notion of D50 (the dose that causes the effect in 50% of consumers exposed to the hazard), in most cases the following relationship thus applies: :D50\ =\ -Ln(0.50)\ / \ r\ \approx 0.7\ / \ r


Comparisons

To compare the dose–response relationships for different effects caused by the same bacterium, or for the same effect caused by different bacteria, one can directly compare the values of r; also, it can be used to evaluate the efficacy of a drugs such as antibiotics. However, it may be easier to compare the doses causing the effect in 50% or 1% of consumers. These are values of D1 (dose causing the effect considered in 1% of consumers exposed to the hazard): * ''
Escherichia coli ''Escherichia coli'' ( )Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. is a gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Escherichia'' that is commonly fo ...
'' (EHEC), haemolytic-uremic syndrome in children under 6 years: 8.4 bacterial cells; * ''Escherichia coli'' (EHEC), haemolytic-uraemic syndrome in children aged 6 to 14 years: 41.9 bacterial cells; * ''Listeria monocytogenes'', severe listeriosis in the general population: 4.2x1011 bacterial cells; * ''Listeria monocytogenes'', severe listeriosis in the susceptible population: 9.5x109 bacterial cells. These examples highlight two important things: # D1 and r depend not only on the bacterium and the effect considered, but also on the belonging to categories of consumers susceptible to the disease; therefore, there are as many dose-response curves as there are pathogens, health effects and sensitivities of exposed individuals; # For the bacteria of the examples above, the orders of magnitude of the values of D1 are profoundly different. The hygiene practices and control measures that food chain businesses must implement against these bacteria are therefore not comparable.


Risk management

While consuming a low dose of pathogenic bacterium is associated with a low probability of disease, infection is still possible. This contributes to sporadic cases of food-borne illness in the population. There is no bacterial concentration in food below which a lack of
epidemic An epidemic (from Greek ἐπί ''epi'' "upon or above" and δῆμος ''demos'' "people") is the rapid spread of disease to a large number of hosts in a given population within a short period of time. For example, in meningococcal infection ...
is guaranteed.


Toxigenic bacteria

Some food-borne bacteria can cause disease by producing
toxin A toxin is a naturally occurring poison produced by metabolic activities of living cells or organisms. They occur especially as proteins, often conjugated. The term was first used by organic chemist Ludwig Brieger (1849–1919), derived ...
s, rather than infection like ETEC. Some synthesize a toxin only when their concentration in the food before ingestion exceeds a threshold, such as
Staphylococcus aureus ''Staphylococcus aureus'' is a Gram-positive spherically shaped bacterium, a member of the Bacillota, and is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often posi ...
and
Bacillus cereus ''Bacillus cereus'' is a Gram-positive bacteria, Gram-positive Bacillus, rod-shaped bacterium commonly found in soil, food, and marine sponges. The specific name, ''cereus'', meaning "waxy" in Latin, refers to the appearance of colonies grown o ...
. The concept of MID does not apply to them, but there is a concentration below which they do not constitute a danger to the health of the consumer.


See also

*
Viral load Viral load, also known as viral burden, is a numerical expression of the quantity of virus in a given volume of fluid, including biological and environmental specimens. It is not to be confused with viral titre or viral titer, which depends on the ...
* Plaque forming unit * Virus quantification


References

*Stella, P., Cerf, O., Koutsoumanis, KP, Nguyen-The, C., Sofos, JN, Valero, A. & Zwietering, MH (2013) Ranking the microbiological safety of foods: a new tool and its application to composite products. ''Trends in Food Science & Technology'' 33 (2): 124–138. *ANSES, the French Agency for Food, Environmental and Occupational Health and Safety, classifies in susceptible populations 'persons with a higher than average probability of developing, after exposure to the food hazard, symptoms of the disease, or serious forms of the disease' {{Refend Bacteria Disease transmission