Antimicrobials use and antimicrobial resistance in humans and food-producing animals

EFSA, EMA and ECDC have published a joint report on the correlation of the consumption of antimicrobials by food-producing animals and humans and the occurrence of antimicrobial resistance. Not surprisingly, they found positive associations between antimicrobial consumption and antimicrobial resistance in humans and food-producing animals but also, in some cases, positive associations between antimicrobial consumption by food-producing animals and resistance to antimicrobial agents exhibited by bacteria in humans.

'Mycobacterium tuberculosis bacteria'
by NIAID under a CC license

Antimicrobial resistance is a topic that I re-visit from time-to-time. In brief, antimicrobial resistance is the phenomenon where a bacterium acquires resistance towards an antimicrobial agent. This may happen via a spontaneous mutation or via gene transfer. The emergence of antimicrobial resistance is a very important issue, regardless of whether the micro-organisms where resistance is developed are, themselves, pathogens or not. Bacteria have the ability for horizontal gene transfer. Thus, once the genes responsible for a specific antimicrobial resistance appear in a microbial population, the propagation of the genes to other microbial populations, including different bacteria, will take place at some point. Obviously, this becomes critical when pathogens acquire such genes, especially when taking into consideration that the antimicrobial agents (antibiotics) we have at hand to fight them are finite (and rather few).

The report of the three agencies highlights a problem that has been known for a while but sometimes still tends to be overlooked. There are vastly different practices across countries with regards to the way that antimicrobial agents are used by doctors and veterinarians to tread human and animal diseases, respectively. To make things worse, residues of veterinary medicines in food-producing animals may also remain in the meat at the time of consumption. As you may suspect, bad practices in either of those fields can give further rise to antimicrobial resistance and, in the longer run, can both accelerate the emergence of antimicrobial resistance of human pathogens.

Given the increasing globalisation of livestock production, as well as the increased mobility of people around the globe, it is necessary to boost efforts for better management of the use of antimicrobial agents, both against human and animal diseases.

This is no simple task, though.

Optimum management requires resources and infrastructure that differ a lot from place to place. Think, for instance, that keeping food-producing animals healthy without resorting to the use of antimicrobial agents needs hygiene, animal-housing and health monitoring practices that come at a cost. On top of that, such animals may be less productive in terms of meat. Such effects discourage the adoption of practices featuring responsible use of antimicrobial agents. There, education, as well as legal measures, have a strong role.

In any case, however, the fact that the task in question is difficult that doesn't mean that the effort should halt. At least not until we find other, reasonably effective ways to deal with pathogens.

Antibiotic resistance and food (again)

'Mission San Juan Capistrano bells'
by Ballookey Klugeypop under a
CC license

Antibiotic resistance is the case where microorganisms become able to survive after exposure to antibiotics. Antibiotic resistance is not a new phenomenon. When resistance to multiple antibiotics is observed in pathogens then things become particularly alarming. Infections by multidrug resistant pathogens (superbugs) are very difficult - and sometimes impossible - to treat, especially when the patient's organism is weak.

I've written on superbugs before but recently antibiotic resistance re-surfaced in the news in a different way. As described by Maryn McKenna, seafood imported from South Korea to Canada was found with Pseudomonas bacteria, which turned out to carry a gene that enables the synthesis of a carbapenemase enzyme.  This is alarmingly important for a number of reasons:

• Carbapenamase enzymes can inactivate carbapenem, an antibiotic of last resort.
• Seafood is sometimes mildly processed, in some cases deliberately to retain flavour and texture, while in others it may simply be undercooked. In such cases, the bacterium found would be likely to survive.
• Non-resistant bacteria can acquire antibiotic resistance from resistant ones via horizontal gene transfer involving plasmids

If consumed, the bacteria in question could possibly make it to the gut. As they are not pathogens they would not pose a direct problem themselves but they would be likely to transfer antibiotic resistance to the gut flora bacteria. I am not aware of the probability of such chain of events but should it happen in individual consumers, it would create inside them a population of bacteria resistant to a class of last resort antibiotics. That's not a good thing to happen!

Carbapenem resistance in the food production system has been a concern previously. Unfortunately, this needs to be considered in tandem with the occurrence of carbapenem resistant infections that seems to be on the rise in Europe (but still under control).

The Canada seafood case highlights a different route of concern, where the consumers may be exposed to resistant non-pathogens (with the potential to be found on a variety of foodstuffs) rather than resistant pathogens, directly, or antibiotic residues in food, which could - in turn - potentially invoke antibiotic resistance.

There is a need for better monitoring of the various routes that can lead to antibiotic resistance. This is no small challenge, though (and it comes with a certain price tag)! However, without any need to panic, it is essential we understand what the risk is and adapt our food processing (and healthcare) practices accordingly. Such approaches work on the prevention front. Hopefully, we'll also make some more breakthroughs on the antimicrobial front, as well!

Acrylamide: A shady side of yumminess

'Homemade freedom fries'
by sean dreilinger under
a CC license

EFSA has recently published a draft scientific opinion indicating concerns regarding acrylamide intake and its potential role as carcinogen.

If that is as alarming as it sounds, why don't we take action now to eliminate it from our food?

And, at any rate, what can we do about it?

The brief answer to the latter is that acrylamide is not easy to get rid off entirely, as is forms during common food processing, both at the kitchen level and the industrial level. But, yes, we can reduce it further by modifying the cooking and processing steps. "Brown it lightly, don't burn it" is the simple rule to follow!

The answer to the former, however, is a bit more difficult to give using hard data to back it up, because total acrylamide intake is normally rather low and there is not too much evidence on the effect of acrylamide consumption on consumers, yet. So right now, reasonable caution is the most prudent thing one can advise.

OK. If you are still with me and can bear with me for a little longer, here is the slightly more detailed version of the story...

Acrylamide is a chemical compound formed in starchy foods when they are heated at high temperatures, starting at low rates from about 120 ^oC,  for prolonged time. It is just one of the many products of the so-called Maillard reaction, which actually is a large set of reactions, that take place when amino acids (the building blocks of proteins) and reducing sugars are heated together. The Maillard reaction products contribute considerably to the brown colour and the characteristic taste and flavour of baked, grilled, fried, etc. products.

Most of the food-contained acrylamide comes from the consumption of potato crisps, fried potatoes and coffee. Other starch-containing food that have been subjected to high temperatures, such as rusks, bread, etc., also contain acrylamide but typically in lower (or much lower) concentrations. EFSA's draft opinion quotes a mean intake that ranges from 0.3 to 1.9 μg/kg body weight. Indicatively, smoking also adds to the acrylamide intake by 0.5 to 2  μg/kg body weight. Once consumed, acrylamide is metabolised either to N-acetyl-S- (3-amino-3-oxopropyl) cysteine or Glycidamide. It is mainly the latter metabolic product that raises the concerns for acrylamide's genotoxic and cancerogenic properties.

So how big is the risk?

EFSA follows the Margin of Exposure (MOE) approach. MOE is the ratio between the dose where no adverse effect is observed to the estimated human exposure. To estimate the risk level, MOE is compared with the product of the uncertainty factors that need to be taken into consideration. Those are factors applied to data obtained from animal studies and account for the various differences between species (taking into consideration safety factors, as well). In the current case of examining acrylamide's genotoxic and cancerogenic properties, EFSA calculated a MOE much higher lower than the product of the uncertainty factors, thus indicating concern.

Acrylamide production during food processing is not a new story. In fact, there are indications that acrylamide content has been reduced lately as awareness for acrylamide concerns increases.

Currently there is little evidence through human studies on any alleged effects of acrylamide. Evidence comes mostly from animal studies, where acrylamide's consumption effects have been observed. Such toxicological studies often study consumption regimes unrealistically higher than normal human intake, within non-typical diets. The latter implies that the ingestion of acrylamide is not accompanied by ingestion of other ingredients that may - in vivo - play a role in its actual effect. Despite those uncertainties, that doesn't mean that acrylamide concerns should be dismissed. Rather that caution should be advised and studying of the issue should continue.

In Europe, sampling and analyses for acrylamide content in food has been ongoing for several years now. Parallel to that, the food industry has been using an acrylamide "toolbox" in an effort to reduce acrylamide content in processed food. At the industry level, there is also the possibility to use different raw materials (less prone to acrylamide formation), enzymes (to break down or modify the protein content that contributes to acrylamide formation), etc. All those are steps towards the right direction and take place in parallel to the efforts to fully characterise the risk.

Acrylamide, as mentioned previously, also forms during cooking food at home. There, the rule of thumb is "Lightly brown it - Don't burn it!". Which goes together with the common sense advice to maintain a balanced diet with variety in the foods consumed.
 
Note: Various organisations across Europe have produced relevant FAQs or info-sheets. If you are in Europe, it's worth checking at your national Food Authority's website. E.g., BfR (DE), ANSES (FR), EFET (GR), FSAI (IE), FSA (UK), AECOSAN (ES), etc.

Foodborne diseases: The case of the innocent-looking berries

'Berries' by Jeremy Cherfas
under a CC license

It's been about two-and-a-half years now that cases of hepatitis A have been appearing in Europe. Further analysis, as quoted by the European Food Safety Authority, has shown similarities in the viral genome across the majority of those cases. That is an indication for a common source of infection, which - currently - is believed to be frozen berries. So far, 11 countries in Europe are known to have been affected. (A similar-sounding story that appeared in the US seemed to be coincidental and it was attributed to imported pomegranate seeds.)

Technically, the term "berries" covers a wide variety of fruits although it is normally used to describe small, juicy, bright-coloured fruits, such as blueberries, strawberries, blackberries, blackcurrant, etc. They can be eaten raw but they are also extensively used as ingredients either raw or as preserves in other foodstuffs, such as creamy desserts, parties, flavoured ice-creams, various alcoholic beverages, etc.

In some of those products the berries find themselves in having had minimal - and sometimes non-thermal - treatment. That provides ground for pathogens and, in the case of hepatitis A, the hepatitis virus that may lie on the surface to survive.

Locations of the hepatitis A outbreaks attributed
to a common, continuous source in the EU/EEA,
possibly frozen berries; Compiled from Source:
European Centre for Disease Prevention and
Control and the European Food Safety
Authority,  2014; Outbreak of hepatitis A in
EU/EEA countries - Second update. EFSA
supporting publication 2014:EN-581. 14 pp.

Hepatitis A is a disease usually transmitted via the consumption of food or water contaminated by infected fecal matter. It has a very long incubation period that can reach up to 50 days and, in some cases, it is asymptomatic, i.e., the people infected do not display any symptoms of illness (but they can transmit the virus).

While the food law in Europe requires food businesses to keep traceability records when receiving or providing food products or ingredients to other food business operators, including retailers, linking the hepatitis A outbreaks to a particular contaminated ingredient and tracing it back to a single source has proven to be very challenging.

The main reasons for that are the long incubation period of the disease and the complexity of the food chain, especially when dealing with multi-ingredients food products. Thus, when a case of hepatitis A is confirmed, pinpointing the source of the infection would require the patient to identify foodstuffs he/ she had consumed over a very long time (up to 50 days before the onset of symptoms), an exercise that is nearly impossible to execute in a fully accurate way. Then the ingredients and the processing of the individual foods needs to be considered in order to select the ones likely to have been vehicles for the virus. Then those should be traced back the food chain. With luck, superimposing the trace-back routes of different cases infected by the same virus strain could, at some point, help identify the starting point of the contamination.

Although hepatitis A is not normally a deadly disease (for reasonably healthy adults), it can be a rather "unpleasant" experience. Thankfully, consumers can minimise the risk by boiling frozen berries for about one minute; this will destroy the virus if present on the berries. Simply rinsing the berries with tap water may not be enough; depending on the type of the berries, they may have a large total surface with lots of niches where water cannot really reach (not to mention that fruits tend to have a hydrophobic surface... which reminds me of an older - yet irrelevant - post).

Moral line of the story - if there needs to be one: Risk communication, i.e., telling consumers (and businesses) what the hazard, the risk and the reasonable mitigation measures are, preferably in plain language, can be very effective when everything else fails.

Thirsty?

'Water walker' by Navdeep Raj
under a CC license

What do you ask for when you feel thirsty?
Water, maybe?

It doesn't take much thought to reply to that, does it?

A couple of days ago (on 18/11, to be precise), The Telegraph featured an article titled "EU bans claim that water can prevent dehydration". The article comments negatively on legislation that follows an EFSA opinion, which rejects a health claim on the potential of water consumption against dehydration. The EFSA opinion is not a very new story but it seems to have resurfaced. The said article was also in slashdot yesterday, so I assume that it has received plenty of attention world-wide by now.

Interesting article, with negative bias, regardless of the fact that both quotes and facts are provided. The article suggests that EFSA's opinion and the subsequent legislative act are really against common knowledge and are, thus, wrong. Apart from that, according to the article, the whole process has been rather expensive (for the taxpayer). Only at the very end of the text does a supportive (for EFSA) opinion appears, with no further comments given.

Well, let's see where this case stands. The claim that was submitted to EFSA for their opinion was "regular consumption of significant amounts of water can reduce the risk of development of dehydration and of concomitant decrease of performance". It was submitted by two German professors (some internet sources say they are consultants for the bottled water industry) under Art. 14 of Regulation EC/1924/2006, which covers claims for the reduction of disease risk.

EFSA said (and repeated) that the submitted claim did not meet the requirements of Art. 14 for the reduction of disease risk. The European Federation of Bottled Water seems to agree. Dehydration is a state of the body and - itself - is not a disease, although it can be a side-effect/ symptom of various diseases. I admit, however, that EFSA's opinion has been written in a rather complicated way, where they seem to somehow accept dehydration as a disease before concluding that the requirements of the Regulation are not met!!! Strange....

To make things interesting, the responsible EFSA's panel had given favourable opinions on the role of water for "maintenance of normal thermoregulation" and for it being a "basic requirement of all living things" - both claims falling under Art. 13 of Regulation EC/1924/2006, which includes claims on "the role of a nutrient or other substance in growth, development and the functions of the body". In order words, it seems plausible that the claim was filed under the wrong classification. If that was really the case, EFSA should not be the one to blame for that.

It is clear that all nutrition and health claims submitted for consideration should be rigorously processed. That 's what the law foresees and that 's what is needed in order to protect the consumer and maintain a competitive - but fair - market. Submitting obvious (or stupid) claims doesn't mean that they won't go down the processing pipeline. And although that this comes with a price-tag, there's no safe way to go around that; there is no "obviousness" clause that would allow the EC (or EFSA) to accept or reject a proposed claim.

Going a bit beyond, I really wonder, what is the reason of having a health claim supporting that water can help against dehydration? If it is common knowledge (which it is), why apply for it? In any case, the EU law would prevent such a claim phrased in a way that it would benefit a particular product, since the beneficial function is performed by any drinkable water (yes, including tap water :-)

Was it an effort to prove that the system is broken? If that was it, then point taken. And then immediately, point put aside. Every system that is open to all and is committed to dealing with all has similar weaknesses. I've got nothing against improving a system, if that is needed, but passing the obvious through formal channels so as to see what happens is a questionable practice...