**1. Introduction**

#### **1.1. Definition and mechanisms of food poisoning**

Food poisoning is a term applied to an acute intestinal disease acquired by the consumption of food or drinks (e.g. juice, water, wine). The toxic agents responsible for food poisoning include the following: microorganisms that occur naturally in humans, animals and/or the environment; parasites, in particular intestinal worms and others that can be transmitted through contaminated food and water; contaminants, adulterants and poisoning agents that can occur in food through normal modes of contamination or by deliberate addition; naturally occurring toxins that occur in food naturally or produce toxins inside the food through normal biological processes; agro-chemical and veterinary drug residues as a result of their purposeful use; spores and prions such as the bovine spongiform encephalopathy or its human variant responsible for the Creutzfeldt-Jakob disease; persistent organic pollutants that accumulate in soil, plants, animals and the human body; and heavy metals such as lead, mercury, cadmium and others; and various allergens [1–5].

#### **1.2. How does food poisoning occur?**

Food poisoning is often confused with food allergy and food adverse effects, which are, respectively, an immune-mediated reaction and a clinically abnormal response, attributed to an exposure to a food or food additive [1, 6]. Food poisoning results from exposures to toxic agents present in the food that may lead to harmful effects based on the reaction of the body to these agents or the food itself. Exposures may happen through ingestion, contact or transdermal, or inhalation. The resulting effects of the exposure may be localized, or general‐ ized; they may also be topical or systemic [7, 8].

At the core, the adverse functional or morphological changes observed upon clinical or histopathological examinations are almost invariably a consequence of biochemical lesions [9]. This means that, in general, toxicity arises from interaction of the offending toxic element or its derivatives with molecular sites of the host system that leads to the derangement of the biochemical processes involved in the normal function and regulation of the cells, tissues, organs and systems of the body. Hence, it is the overloading of the biochemical processes, because of the simple presence or the excessive quantities of the offending toxic agent, beyond the capacity of the host systems to adapt and restore to these processes at their normal level that leads ultimately to cell, tissue, or organ injury or the elucidation of the toxic effects as signs and symptoms [10–12].

The most common microorganisms involved in food poisoning are bacteria such as *Bacillus cereus*, *Staphylococcus aureus*, *Clostridium botulinum*, *Vibrio cholerae*, *Escherichia coli* and *Shigella* species and others that produce toxins that cause foodborne intoxications. *Listeria monocyto‐ genes* can grow at temperatures below 5°C and so can multiply in refrigerated food but can be eradicated by thorough cooking and by pasteurization. Other microorganisms such as *Norovirus* and *Rotavirus* as well as parasites such as *Giardia* spp. and *Cyclosporidium* spp. can also be involved [13]. The main reason why microorganisms predominate in causing food poisoning is that they have the ability to grow in the foods and to dwell there even when reduced to spores, particularly bacteria. Moreover, even when bacteria do not grow in the food itself, they may be carried by the foods that are notoriously known to be involved in outbreaks of dysentery [14, 15]. It is important to note that most foods carry microorganisms, but some foods are more prone in being potential carriers of food poisoning microorganisms; these foods are principally raw meat, poultry, milk, seafood and raw vegetables [16, 17].

The microorganisms inducing food poisoning are often associated with the gut of humans, animals and birds. *Clostridium perfringens* forms part of the normal gut flora and is widely present in food and the environment. Its spores can survive heating to standard cooking temperatures particularly when food is kept warm for prolonged periods after cooking; its effects are mediated by an enterotoxin produced by the bacterium after ingestion. It should be noted that any food contaminated with faeces has the potential to cause food poisoning as well as contact with ill animals [18, 19]. It should be noted that *Campylobacter* spp. is the commonest reported food poisoning caused by bacteria worldwide. It typically causes fever, diarrhoea and abdominal cramps. The infection is often contracted by eating undercooked poultry, unpasteurized milk, untreated water and food that has been contaminated. Two species account for the majority of infections: *Campylobacter jejuni* and *Campylobacter coli* [20, 22].

Raw meat is often a direct food poisoning hazard as it contains microbes; it is also an indirect factor of food poisoning through cross-contamination of cooked meats, other foods and water. It has been established that raw meat can contain *Salmonella* that may affect food handlers or they may transfer to other foods. It is also known that *Salmonella* may grow in meat products kept at room temperatures; products such as meat pies, sausages, cured meats (ham, bacon and tongue) and sandwiches are prone to this effect as they are normally allowed to stand at room temperatures during or before being processed or cooked [23–25]. Besides meat, water, a major component of most foods and drinks, is often contaminated as explained above or it may be polluted from its sources and thus carry with it substances that may cause food poisoning [26–28].

Furthermore, substances released in foods by insects, bacteria or other living microorganisms, hence called "toxins", may also cause food poisoning. This is well documented in the case of mushroom toxins and ciguatera fish poisoning. With regard to fish, the toxin is produced by a marine alga *Gambierdiscus toxicus*. Ciguatera fish poisoning occurs when toxins created by dinoflagellate microorganisms are passed up the marine food chain and bioaccumulate in large fish such as barracuda, grouper, red snapper, kingfish, coral trout and others [29, 30]. It is important to note that these toxins are not destroyed through cooking, smoking or freezing, they are odourless and tasteless and do not alter the appearance of the fish.

Anothertype of fish poisoning is scombroid poisoning, which results from improper handling and refrigeration of fish containing high levels of naturally occurring histidine. Contamina‐ tion with bacteria will convert the amino acid histidine into histamine, causing symptoms similar to allergic reactions, which occur very rapidly; the symptoms include headache, abdominal cramps, diarrhoea, itching, flushed face, dry mouth, heart palpitations and difficulty breathing. Scombroid poisoning affects fish from the Scombridae family, such as tuna, mackerel, skipjack and bonito. It can also affect other species, such as herring, blue‐ fish and sardines [31–33].

The other type of fish poisoning is shellfish poisoning that is associated with species found in temperate and tropical areas, such as oysters, clams, cockles, mussels, scallops, crabs and lobsters. These fishes ingest toxins produced by dinoflagellates and produce diarrheic shellfish poisoning, neurotoxic shellfish poisoning or even paralytic shellfish poisoning, which is characterised by the numbness of face arms and legs, loss of coordination and dizziness. In severe cases, respiratory failure and paralysis may occur, leading to death; sometimes, amnesic shellfish poisoning occur, which produces seizures, muscle weakness or paralysis and disorientation. Permanent short-term memory loss has been observed and, in severe cases, can lead to coma or death [30, 33].

Finally, puffer (Fugu) fish poisoning is caused by a tetrodotoxin accumulating mainly in the liver, intestines and ovaries of puffer fish, ocean sunfish, globe fish and porcupine fish. Symptoms of poisoning include profuse sweating, salivation, headache, hypothermia, heart palpitation as well as neurological symptoms, such as numbness, loss of coordination, tremors and paralysis [29].

Chemicals such as pesticides, fungicides, preservative agents, food additives, colorants and taste-enhancing or altering chemicals may also cause food poisoning [34]. Some pesticides such as lindane and thiosulfan have been covertly and illegally used to harvest fish from rivers in some countries. Similarly, carbofuran was used to harvest birds for the bush meat trade in some countries in East Africa. The poisoned fish and bush meat are sold to unsuspecting customers who may be subsequently poisoned [35–38].

It should be noted that some of these chemicals found in foodstuffs in small doses but taken more frequently can lead to chronic poisoning, whereas the others when ingested in high doses may result in acute food poisoning. This occurs when recently treated and unwashed fruits or vegetables that are contaminated with pesticides are eaten [39, 40].

The above remarks suggest that in most cases, the exact mechanism of toxicity is not known, but the time between the exposure and the resulting toxic effects determines whether an exposure is acute or chronic. In an acute poisoning incident, the effects occur almost immedi‐ ately after an exposure or conventionally within 24 hours. When the effects of toxicity appear or become apparent after 1 day to several years later from the actual date of first intake of the offending agent, this is referred to as "chronic poisoning" [41].

Furthermore, the exposures may be deliberate or accidental. Deliberate exposures occur when the victims expose themselves to toxic agents with the intention to harm themselves or to seek attention from the people close to them [41]. This could happen when a person decide not to preheat or warm the food before eating with the very intent of falling sick to get the attention or sympathy of their loved ones or avoid performing certain acts. This kind of exposure results in suicide or para-suicide depending on whether the victim had or did not have actual intention to die. Other instances are simply bizarre like the old practice of adding tablets of lead to wines, despite knowing the dangers of acute lead poisoning [42–45].

On the other hand, food has been used to intoxicate other people. This deliberate exposure whereby the manipulation of food or drink by a third party, whether adulteration, contami‐ nation or addition of high doses of a chemical, drug or other substances in order to harm the intended victim is usually done for criminal or emotional purposes [46]. Motivations for criminal poisoning include the desire to rob, to punish someone, to benefit financially, get political power, to end the miserable life of a loved one, to eliminate an enemy or to simply to terrorise [46–50].

For instance, it is well accepted that the Emperor Claude was poisoned by his wife, who gave him a meal of poisonous mushrooms of *Amanita phalloides*, which contain amanitin polypep‐ tides, so that upon his death, his son, Nero could become the king. Amygdalin, a glycoside yielding hydrocyanic acid (HCN) through hydrolysis, is present in the family of Rosacea species such as in certain seeds of apples, cherries, peaches and plums. HCN is a chemical that inhibits the action of the enzyme cytochrome oxidase and prevents the uptake of oxygen by cells. As little as 0.06 g can cause death in humans; hence, it has been reportedly used as an assassination weapon in the famous killing of the Russian monk, Grigori Yefimovich Rasputin [48, 51].

Some would resort to criminal deliberate intoxication in order to get attention as in the case of Munchausen syndrome by proxy [52, 53]. Many authors have reported on drug-facilitated sexual assaults where a variety of medicines and drugs of abuse have been added in drinks or foods/meals of unsuspecting victims (Gilfillan, 1965; Douglas et al., 1992; Uges, 2001; Weber et al., 2009) [54–56]. The author is also aware of cases where food poisoning has been perpe‐ trated with the intent to kill. In one dramatic case, a woman crushed a glass bottle and added the fine particles in the porridge and gave it to the three children of a widowed man she wanted to marry. The two kids younger than 5 years old died due to severe intestinal haemorrhages; the girl who was 7 years old survived as she did not eat much as she sensed that something was not right with the porridge.

Accidental food poisoning occurs when the victims unwittingly ingest the offending food or drink with no intent or expectation of harm [57]. This occurs due to negligence, lack of knowledge or simply as a random event. Sometimes it might be due to a confusion of pills looking as candies or edible legumes with their look-alike toxic species. Such a case happened in South Africa, where the author attended to children aged 4 to 8 years old who had ingested colourful multivitamin sugar-coated tablets and colourful chlorpromazine tablets that found at municipal dumpsite. They had mistaken them for candies and ate or swallowed them; two of the seven children died.

Similarly, there was an outbreak in Cambodia where adult villagers confused the edible *Melientha suavis* with the non-edible and toxic *Urobotrya siamensis*, both plants from the Opiliaceae family[58].Inother settings,masspoisoningincidentshaveoccurredthrougheating of birds carrying a toxic substance from plants. This happened in Algeria more than 50 years ago. Edmond Sargent, one of the leading African toxicologists, proved through experimental study that the poisonous birds or pigeons of Algeria had been carriers of cotinine, a poison‐ ous alkaloid that is not harmful to the birds but to the humans who ate these birds [59, 60].

Other famous cases include the mass intoxication of Greek soldiers by eating honey from *Rhododendron ponticum* and *Rhododendron flavum*. The honey grown from these plants had high doses of diterpene grayanotoxins. In other settings, people have been intoxicated from teas brewed from plant parts or after consuming leaves, flowers or seeds from toxic plants (Dickstein and Kunkel, 1980; Bain, 1985; Joskow et al., 2006) [61–63]. Accidental food poisoning incidents have been reported after people consumed recently sprayed maize that was obtained illegally. The author knows of an incident in South Africa where 10 family members where brought at the hospital after consuming such maize. Of the 5 children younger than 7 years who ate this food, 2 died.
