In this article, we're diving into the world of Listeria monocytogenes, a resilient bacterium responsible for severe foodborne illness, particularly affecting pregnant women, the elderly, and those with weakened immune systems. We'll explore the unique survival abilities of this Gram-positive bacterium, its high fatality rate in foodborne outbreaks, and why it's a primary concern in ready-to-eat foods like deli meats, cheeses, and smoked seafood. Discover the challenges of controlling L. monocytogenes in food production and the differences in regulatory standards between the U.S., EU, and Japan, as we shed light on best practices for keeping food safe from this persistent pathogen.
Understanding Listeria monocytogenes: A Domino Effect from its Habitat
Before we delve into this cascade of knowledge, it would be helpful to first read through a basic article on Gram staining and microbial characteristics available on our blog. This foundational reading will pave the way for the smooth flow of understanding that follows, akin to a well-aligned domino fall.
Let's break it down:
- L. monocytogenes , a Gram-positive bacterium, is found in the guts of animals like sheep, cows, and pigs. But, it's not just a homebody; this bacterium can thrive in a variety of environments. Originally, it was seen as a troublemaker only for goats and sheep.
- Now, although L. monocytogenes is a Gram-positive bacterium, which usually suggests a toxin-producing type of food poisoning, it breaks the this rule. Despite being Gram-positive, it causes infection-based food poisoning. A bit of a rebel in the bacterial world, isn’t it?
- L. monocytogenes loves a warm 37°C, typical of mammalian body temperature, for partying and multiplying. But it's also quite comfortable in the chilly environment of a fridge, a trait unlike its Gram-negative, infection-causing counterparts. In this sense, L. monocytogenes is like a chameleon, adapting to its environment.
- As a Gram-positive bacterium, L. monocytogenes can tough it out in harsh conditions like dryness and high salt. This is quite the plot twist, considering most infection-causing food poisoning bacteria are Gram-negative and not so hardy. L. monocytogenes stands out as the Hercules of food poisoning bacteria in terms of environmental stress resistance.
- Preferring the intestines of mammals, L. monocytogenes is an facultative anaerobe. It easily produces organic acids outside the cell and is quite comfortable in acidic environments. Think of it as thriving in a vinegar-like setting.
- However, its Gram-positive nature means it's not so tough against certain chemical agents with hydrophobic functional groups. So, creating a selective culture medium for L. monocytogenes isn't as straightforward as for Gram-negative bacteria like E. coli or Salmonella.
Understanding L. monocytogenes is like a domino effect, where each piece of information smoothly leads to the next.
The High Fatality Rate of L. monocytogenes Food Poisoning
L. monocytogenes is a foodborne pathogen notorious for causing severe symptoms and a high fatality rate. This bacterium has been responsible for the highest number of deaths in food poisoning cases in countries such as the United States, Canada, and Denmark. For instance, in 1985 in the United States, an outbreak linked to soft cheese resulted in 47 deaths, marking it as the deadliest food poisoning event in American history. Similarly, in Canada in 2008, an outbreak associated with deli meats led to 22 fatalities, which is also the highest number of deaths from food poisoning in Canadian history. In Denmark, 2014 witnessed 15 deaths due to an outbreak linked to sausages, again the highest in the country's history of food poisoning incidents.
L. monocytogenes food poisoning is characterized by its high number of fatalities. In the United States, for example, around 2,500 people are infected each year, with about 500 of these cases, or one-fifth, resulting in death.
L. monocytogenes : A Significant Threat to Pregnant Women, the Elderly, and the Immunocompromised
Another notable aspect of L. monocytogenes is that about 40% of all cases occur in pregnant women, with a significant number of cases also found in the elderly. This distinguishes L. monocytogenes from other foodborne pathogens: it specifically targets individuals with weaker immune systems, such as pregnant women and older adults.
In healthy young people, L. monocytogenes infection might only cause symptoms like fever and diarrhea, barely distinguishable from a common cold. As a result, many healthy young individuals who contract L. monocytogenes might mistakenly think they've just caught a cold. However, for pregnant women and the elderly, the initial symptoms might seem like a cold too, but can rapidly progress to more severe conditions. Pregnant women are at risk of miscarriage, while older adults may develop life-threatening conditions like meningitis.
This vulnerability in pregnant women and the elderly is largely due to their weakened immune systems, making them prime targets for L. monocytogenes infection.
The Mechanism Behind Severe Infections in the Elderly and Pregnant Women Caused by L. monocytogenes
The process by which L. monocytogenes causes severe infections in vulnerable individuals like the elderly and pregnant women is complex. After consuming contaminated food, symptoms like diarrhea and fever may subside within 24 hours. However, for those with weakened immune systems, such as the elderly and pregnant women, a latent period follows before severe symptoms develop.
When foreign bacteria like L. monocytogenes enter the intestinal epithelial cells, they are captured by macrophages, immune cells known as M cells, present between these cells. The invaders are then intended to be digested inside a compartment known as a lysosome within the macrophages. In healthy individuals, L. monocytogenes is typically eliminated at this stage, leading to a resolution of symptoms similar to a common cold.
However, L. monocytogenes has a trick up its sleeve. After being engulfed by macrophages, it initially resides within a compartment called a phagosome. Normally, this phagosome would fuse with a lysosome containing digestive enzymes to destroy the bacteria.
But L. monocytogenes produces an enzyme, listeriolysin O, allowing it to escape from the phagosome before this fusion can occur, akin to a circus performer making a dramatic escape from a water-filled bag.
This ability enables L. monocytogenes to survive within macrophages.
In the elderly, the bacteria can travel through the bloodstream to the brain and spinal cord, causing meningitis and a high risk of death.
In pregnant women, it can take up to three weeks for serious complications like neonatal infection or miscarriage to occur. This delay is thought to be due to the time L. monocytogenes needs to break through the membranes surrounding the fetus and invade the amniotic fluid.
This lengthy process explains why L. monocytogenes infections can take time to develop into severe conditions in the elderly and pregnant women. The long incubation period, which can be as much as three weeks, makes it extremely difficult for doctors to identify the contaminated food that caused the infection. This is especially problematic if only a single elderly person or pregnant woman in a household develops listeriosis.
L. monocytogenes : A Risk in All Uncooked Foods, Not Just Cured Meats and Cheeses
One crucial way L. monocytogenes differs from other pathogens like E. coli O157 is in its ability to survive almost anywhere. Typically, infection-causing foodborne bacteria are Gram-negative, which don't have strong resistance when released into the environment. However, L. monocytogenes is a notable exception. Despite being an infection-causing bacterium, it is Gram-positive, allowing it to survive and multiply in a wide range of environments. This characteristic makes preventing L. monocytogenes food poisoning quite challenging.
For those interested in the fundamental differences between Gram-positive and Gram-negative bacteria in environmental characteristics, please refer to the following article:
In terms of food contamination, cured meats like prosciutto, raw meats, and natural cheeses are commonly implicated, with many food poisoning cases in the United States and the European Union linked to these foods.
However, the risk of L. monocytogenes doesn't end there. All types of uncooked ready-to-eat (RTE) foods carry a risk. This includes sandwiches made with cured meats or natural cheeses, as well as smoked seafood products like smoked salmon, which are often involved in L. monocytogenes food poisoning incidents and are considered highly contaminated.
Furthermore, in Japan's "raw food culture," RTE foods like seasoned cod roe (mentaiko) and salmon roe (ikura) are also frequently contaminated with L. monocytogenes .
Thus, some level of L. monocytogenes contamination in foods seems somewhat inevitable. However, there is no need to worry about foods that are intended to be cooked before eating, as L. monocytogenes is not a heat-resistant spore-forming bacterium and can be effectively killed through standard pasteurization processes.
On the other hand, foods sold to be consumed without further cooking (RTE foods) must be handled with great care, as they all pose a potential risk for L. monocytogenes food poisoning.
The Danger of Long-Stored Foods in the Refrigerator
Another characteristic of L. monocytogenes that raises concerns is its ability to grow at temperatures as low as 10°C or below. This means that foods stored in the refrigerator for a long time are at a higher risk of causing L. monocytogenes food poisoning.
Particularly risky are those ready-to-eat foods taken directly from the fridge and eaten without further heating. Items such as past-due natural cheeses, cured meats like prosciutto, smoked salmon, or even sandwiches deserve special attention. It's crucial to be vigilant about these foods, especially if they've been sitting in the refrigerator for an extended period.
Contamination in Factories
L. monocytogenes is also a concern in factory settings, particularly in environments like drainage areas. These areas are often cleaned less frequently compared to production lines or floors, primarily due to the difficulty in physically scrubbing them with brushes. As a result, various bacteria, including L. monocytogenes , can easily form biofilms on the walls of the drains, creating a resilient survival environment.
When high-pressure hoses are used to clean these drains, aerosols can be created, dispersing fine water droplets into the factory air. These droplets can carry bacteria, including L. monocytogenes , potentially leading to secondary contamination of food products. This highlights the importance of thorough and careful cleaning practices in food production facilities to minimize the risk of L. monocytogenes contamination.
What is the Minimum Infective Dose of L. monocytogenes ?
The exact dose-response model for L. monocytogenes in humans has not yet been fully established. However, based on current case data from around the world, it is believed that food containing low concentrations of L. monocytogenes , specifically less than 100 CFU (Colony Forming Units) per gram, poses minimal risk (FAO/WHO, 2004).
Note: A dose-response model refers to a model that relates the probability of disease occurrence to the amount of pathogen present in food.
Moreover, the European Food Safety Authority (EFSA) estimates that, in healthy individuals, 92% of listeriosis cases occur only when the intake exceeds 105 CFU per meal across all age and sex groups (EFSA Panel on Biological Hazards, 2018).
- This means an intake of more than 105 CFU per meal is necessary for infection.
This estimate assumes an average portion size of 50g, which corresponds to a concentration of L. monocytogenes in cooked food at the time of consumption being greater than 2000 CFU/g (or 2×103 CFU/g).
Therefore, it is believed that food containing a concentration of L. monocytogenes as low as 100 CFU/g or less, which is one-tenth of the aforementioned infective dose, poses minimal risk.
However, it is important to note that these are estimates based on data from healthy adults, and individuals with underlying health conditions or weakened immune systems may develop the disease at lower bacterial counts. This point will be discussed further later on.
Differing Tolerances for L. monocytogenes in Food between the US and the EU
There are different standards set by the United States and the European Union regarding the permissible levels of L. monocytogenes in food.
United States: The standard is essentially a zero tolerance policy, where no more than 1 cfu (colony forming unit) of L. monocytogenes per 25g of food is allowed (which translates to <0.04 cfu/g). This means that the allowable level is effectively zero.
European Union: In contrast, the EU allows up to 100 cfu of L. monocytogenes per gram of food. Within the EU, this standard is further divided into two categories based on the food's design and its potential for L. monocytogenes growth during distribution:
- For foods designed not to support the growth of L. monocytogenes during distribution (for example, those with adjusted water activity or pH levels that are not conducive to L. monocytogenes growth), up to 100 cfu of Listeria per gram is permissible.
- For foods that can support the growth of L. monocytogenes during distribution, food manufacturers are permitted to set the use-by date such that the concentration of L. monocytogenes does not exceed 100 cfu per gram at any time before the use-by date, assuming the consumer eats the product within its shelf life.
These different approaches reflect varying levels of caution and regulation standards in managing the risk of L. monocytogenes contamination in food products in the US and the EU.
Why Does the US Have a Zero Tolerance Policy While the EU Allows Up to 100 cfu/g for L. monocytogenes ?
The EU's standard of allowing up to 100 cfu/g of L. monocytogenes is based on calculations derived from the minimum infective doses for healthy adults, as mentioned earlier.
In contrast, the United States has adopted a zero-tolerance policy towards L. monocytogenes , which is significantly stricter. One reason for this stringent approach is that there have been cases of listeriosis in immunocompromised individuals with underlying health conditions, even with food contaminated with L. monocytogenes at levels below 100 cfu/g.
Examples of this include cases where
McLauchlin et al.
Listeriosis associated with pre-prepared sandwich consumption in hospital in England, 2017
Epidemiol Infect. 149: e220（2021）
Pouillot et al.
Infectious Dose of Listeria monocytogenes in Outbreak Linked to Ice Cream, United States, 2015
Emerg Infect Dis. 2016 (12):2113-2119
However, this zero-tolerance policy in the US leads to frequent food recalls, sometimes on a monthly basis. Despite these stringent measures, the incidence of listeriosis in the US has not significantly decreased, necessitating the continuation of this strict approach.
Yet, there has been longstanding criticism of the inflexibility of the US's zero-tolerance policy towards L. monocytogenes . In 2021, researchers from major universities and public institutions in Canada and the US jointly authored a paper suggesting a reevaluation of the US's zero-tolerance policy. The paper argued for aligning with international standards like those of the EU.
Farber et al.
Alternative approaches to the risk management of Listeria monocytogenes in low risk foods
Food ControlVolume 123, May 2021, 107601
What are the Standards in Japan?
In Japan, there are only two categories for which standards regarding L. monocytogenes content are established:
- Natural Cheeses
- Non-heat-treated Meat Products (such as prosciutto)
For other ready-to-eat (RTE) foods, no specific standards have been set in Japan. This is a significant difference compared to the United States and the European Union. The Ministry of Health, Labour and Welfare in Japan cites the low incidence of listeriosis as the reason for this. Statistically, there has only been one recognized case of listeriosis in Japan, suggesting that there hasn't been a perceived need to establish standards for other cooked RTE foods.
Before 2014, Japan followed a zero-tolerance policy similar to the United States for the two aforementioned food categories. This meant that no more than 1 cfu of L. monocytogenes per 25g of food was allowed.
However, in 2014, the compositional standards were revised for natural cheeses and non-heat-treated meat products, switching to the EU-style regulation. This change allowed up to 100 cfu of L. monocytogenes per gram of food, aligning Japan's standards with those of the Codex Alimentarius (CODEX).
This shift in policy reflects Japan's effort to harmonize its food safety standards with international guidelines, particularly those set by CODEX.
Codex Alimentarius (CODEX) Guidelines
The Codex Alimentarius, or "Food Code," has established guidelines for managing L. monocytogenes in food products:
- For Foods Where L. monocytogenes Can Grow: Zero tolerance policy is applied (L. monocytogenes must not be detected in 25g of the product).
- For Foods Where L. monocytogenes Cannot Grow: Up to 100 cfu/g is acceptable.
- Additional Flexibility: Regulatory authorities can set flexible standards to ensure consumer safety. Even for foods where L. monocytogenes can grow during distribution, manufacturers can set the use-by date in a way that ensures the concentration of L. monocytogenes does not exceed 100 cfu/g by the time the product is consumed.
In the European Union, the regulations adhere to points 1, 2, and 3 of the Codex.
The United States adheres only to point 1 of the Codex guidelines.
In Japan, for natural cheeses and non-heat-treated meat products, the regulations adhere to point 3 of the Codex guidelines.
The decision by Japan's Ministry of Health, Labour and Welfare to apply point 3 for these specific products stems from the fact that it's not definitively clear that these products won't support the growth of L. monocytogenes . Therefore, manufacturers are required to ensure that the concentration of L. monocytogenes in these products does not exceed 100 cfu/g by the time they reach the consumer.
The Risk of L. monocytogenes in Japan
In Japan, cases of food poisoning caused by L. monocytogenes monocytogenes are extremely rare, with official statistics recording only one case to date. This has led to a longstanding belief that L. monocytogenes food poisoning is almost nonexistent in Japan. However, a nationwide clinical survey of patients in hospitals has revealed a different picture: each year, there are approximately 83 cases of listeriosis (0.65 cases per 1 million people). These infections predominantly occur in infants under one year of age and the elderly, with the death rate being highest among those over 70 years old (with a 20% fatality rate). This indicates that, while still relatively low, listeriosis does occur in Japan.
Okutani et al.,
Nationwide Survey of Human Listeria monocytogenes Infection in JapanEpidemiol.
Infect. 132:769–772（2004）
The sources of these infections remain largely unknown. In sporadic cases where only one or two people are affected, identifying the cause is nearly impossible unless the same genetic strain of the foodborne pathogen is found in food samples from the patients' homes. This issue represents a significant challenge for ensuring food safety in Japan and is a matter that should not be overlooked. It underscores the need for continued vigilance and research to better understand and mitigate the risks associated with L. monocytogenes .
Conclusion: Key Points in L. monocytogenes Management
As we have discussed, contamination with L. monocytogenes L. monocytogenes can potentially occur in any food product, and completely preventing its intrusion is a challenging task. For food manufacturers, the key to managing Listeria involves several crucial steps:
- Preventing Biofilm Formation: In food production facilities, one of the primary strategies is to prevent the formation of L. monocytogenes biofilms through stringent hygiene and sanitation practices. Biofilms in the facility can be a significant source of contamination.
- Controlling Contamination in Ready-to-Eat Foods: When it comes to ready-to-eat foods that might already be contaminated with L. monocytogenes due to unavoidable circumstances, such as during raw material procurement, the focus should shift to preventing the bacteria from multiplying during distribution.
- Adherence to Microbial Standards: Both the EU microbial standards and the current standards for natural cheeses and non-heat-treated meat products (like prosciutto) in Japan allow up to 100 cfu/g of L. monocytogenes at the time of the product's use-by date. However, rather than accepting an increase up to this limit, efforts should be made to keep L. monocytogenes concentrations as low as possible. This requires innovative microbial control methods to ensure that even low-level contamination does not increase during distribution and storage.
In summary, managing L. monocytogenes is not just about preventing its entry into food products; it is also about controlling its growth and spread throughout the food production and distribution process. Employing meticulous sanitation practices and effective microbial control strategies is essential in minimizing the risks associated with L. monocytogenes in food products.
