Toxin-mediated Gastroenteritis - 2024 PDF

Gastroenteritis/Toxin- mediated Gastroenteritis Prof. Dr. Necla TÜLEK 27 November 2024  Learning Objectives List important causes of food poisoning Identify the most common bacteria that can cause food poisoning Describe the main modes for transmittig infectious agents that cause...

Gastroenteritis/Toxin- mediated Gastroenteritis Prof. Dr. Necla TÜLEK 27 November 2024  Learning Objectives List important causes of food poisoning Identify the most common bacteria that can cause food poisoning Describe the main modes for transmittig infectious agents that cause food poisoning Describe the pathogenesis of toxin-mediated diarrhea Explain the mechanisms of damage from enterotoxin, cytotoxins, and invazive organisms Describe the clinical findings in food poisoning Differentiate an invazive infection vs. a toxin-mediated illness based on clinical findings Describe the diagnostic technigues used to identify organisms causing toxin-mediated diarrhea Understands the prevention of toxin-mediated gastro intestinal infections Introduction The word "gastroenteritis" originates from the Greek word gastron, meaning "stomach," and enteron, meaning "small intestine." The word "gastroenteritis" means "inflammation of the stomach and small and large intestine." Medically, gastroenteritis is defined as a diarrheal disease, in other words, an increase in bowel movement frequency with or without vomiting, fever, and abdominal pain. Enterocolitis involves the colon as well as the small intestine, and gastroenteritis includes stomach inflammation. Frequent passing of formed stools is not diarrhoea, nor is the passing of loose, "pasty" stools by breastfed babies. An increase in bowel movement frequency is defined by three or more watery or loose bowel movements in 24 hours or at least 200 grams of stool per day.  Diarrhoeal disease is the second leading cause of death by infectious diseases in children under five years old. It is both preventable and treatable. Each year diarrhoea kills around 525 000 children under five. A significant proportion of diarrhoeal disease can be prevented through safe drinking-water and adequate sanitation and hygiene. Globally, there are nearly 1.7 billion cases of childhood diarrhoeal disease every year. Diarrhoea is a leading cause of malnutrition in children under five years old. According to the duration of symptoms, it is described as acute, persistent, chronic, or recurrent. Acute: 14 days or fewer than 14 days in duration. Persistent: More than 14 but fewer than 30 days in duration. Chronic: More than 30 days in duration. Recurrent: Diarrhea that recurs after 7 days without diarrhea  Acute watery diarrhoea – lasts several hours or days, and includes cholera; Acute bloody diarrhoea – also called dysentery. Watery Diarrhea The most common form of gastrointestinal infection is the rapid development of frequent intestinal evacuations of a more or less fluid character known as diarrhea. Nausea, vomiting, fever, and abdominal pain may also be present, but the dominant feature is intestinal fluid loss. Diarrhea is produced by pathogenic mechanisms that attack the proximal small intestine, the portion of the bowel in which more than 90% of physiologic net fluid absorption occurs. Dysentery Dysentery begins with the rapid onset of frequent intestinal evacuations, but the stools are of smaller volume than in watery diarrhea and contain blood and pus. Fever, abdominal pain, cramps, and tenesmus are common complaints. Vomiting occurs less often. The focus of pathology is the colon. Organisms causing dysentery can produce inflammatory and/or destructive changes in the colonic mucosa either by direct invasion or by production of cytotoxins. This damage produces the pus and blood seen in the stools, but does not result in substantial fluid loss because the absorptive and secretory capacity of the colon is much less than that of the small bowel.  Causes of infectious diarrhea vary among different geographical regions, urban to rural areas, and depend on co-morbidities and host immune status. The most common cause of acute infectious diarrhea are viruses (norovirus, rotavirus, adenovirus, and others). Bacterial stool cultures are positive in less than 5% of cases in most studies. Other than norovirus, important causes of watery diarrhea include Clostridium perfringens, and enterotoxigenic Escherichia coli (ETEC). Bacterial causes are more responsible for severe cases of infectious diarrhea than other infectious etiologies. Overview of causes Infectious or noninfectious causes may be responsible for acute diarrhea. Among infectious causes, a wide variety of pathogens cause acute diarrhea and other foodborne illnesses in resource-rich settings. Infectious diarrheal diseases may be categorized by the portion of the intestine that they are prone to infect, since the presenting symptoms vary by region of the intestine involved in disease. Small bowel – The small bowel functions as a fluid- and enzyme-secretory and nutrient- absorbing organ. Dysregulation of these two processes due to infections of the small bowel leads to a watery diarrhea that occurs in large volume and is associated with abdominal cramping, gas, and weight loss. For the most part, when only small bowel is involved, fever is rarely a significant symptom, and the stool does not contain occult blood or inflammatory cells. Enteric viruses (and specifically norovirus) are the most common causes of watery diarrhea Large bowel – The main function of the large bowel is to absorb fluid and salt and to excrete potassium. Thus, large intestinal diarrheas present with frequent, regular, small- volume, often painful bowel movements. Fever and bloody or mucoid stools are common, and red blood cells and inflammatory cells can be seen routinely on the stool smear. Bacterial pathogens are more common causes of inflammatory, large intestinal diarrhea Bacterial gastroenteritis The bacteria most commonly implicated are Campylobacter Clostridioides difficile Escherichia coli (especially serotype O157:H7) Salmonella Shigella Staphylococci, causing staphylococcal food poisoning Bacterial gastroenteritis is less common than viral. Bacteria cause gastroenteritis by several mechanisms. GASTROINTESTINAL PATHOGENS CAUSING ACUTE DIARRHEA MECHANISM LOCATION ILLNESS STOOL EXAMPLES OF FINDINGS PATHOGENS Proximal small Watery diarrhea No fecal Vibrio cholerae, enterotoxigenic Escherichia coli Noninflammatory bowel leukocytes; enteroaggregative E. coli, (enterotoxin) mild or no C. perfringens, Bacillus cereus, increase in fecal S. aureus, lactoferrin Aeromonas hydrophila, P. shigelloides, rotavirus, norovirus, enteric adenoviruses, G. lamblia, Cryptosporidium spp., Cyclospora spp., microsporidia Inflammatory Colon or distal Dysentery or Fecal Shigella spp., Salmonella spp., Campylobacter jejuni, (invasion or small bowel inflammatory polymorphonucl enterohemorrhagic E. coli, cytotoxin) diarrhea ear leukocytes; enteroinvasive E. coli, Y.. enterocolitica, substantial L.monocytogenes, Vibrio increase in fecal parahaemolyticus, C. difficile, A. hydrophila, P. shigelloides, E. lactoferrin histolytica, Klebsiella oxytoca Penetrating Distal small bowel Enteric fever Fecal mononuclear Salmonella typhi, Y. leukocytes enterocolitica  Food poisoning refers to an illness acquired through consumption of food or drink contaminated either with microorganisms, or their toxins. It usually results in common-source outbreak of diarrhea. Food-borne illness is a significant public health problem. It is a major cause of morbidity and an infrequent cause of mortality Globally, an estimated 600 million (1 in 10) are affected with food- borne illness and 420000 die every year Children under 5 years of age carry 40% of the foodborne disease burden. Food poisoning The production of one or more exotoxins is important in the pathogenesis of numerous enteric organisms. Enterotoxins, which cause watery diarrhea by acting directly on secretory mechanisms in the intestinal mucosa; Neurotoxins are usually produced by bacteria outside the host and therefore cause symptoms soon after ingestion. Included are the staphylococcal and Bacillus cereus toxins, which act on the central nervous system to produce vomiting Cytotoxins, which destroy intestinal mucosal cells and produce the syndrome of dysentery, with bloody stools containing inflammatory cells. Shigella dysenteriae type 1 Vibrio parahaemolyticus Clostrioides difficile. S. dysenteriae type 1 and Shiga toxin– producing strains of E. coli produce potent cytotoxins and have been associated with outbreaks of hemorrhagic colitis and hemolytic-uremic syndrome. Staphylococcal food poisoning Staphylococcal food poisoning is an acute intoxication that occurs when food contaminated with enterotoxin produced by this bacterium is consumed. Staphylococcal food poisoning is considered to be among the most common causes of gastroenteritis worldwide. The presence of staphylococcal enterotoxin in food is usually due to cross contamination of ready to eat food with either raw food or, most likely, contamination from a food handler that is carrying Staphylococcus aureus.  Staphylococcus The genus Staphylococcus currently comprises more than 50 species all known as common colonizers of the skin and mucous membranes of many animal species including humans. One of these different species is S. aureus, so-named because of the color of the pigmented colonies (“aureus” means golden in Latin). Staphylococci cause intoxication from the consumption of food containing preformed staphylococcal enterotoxins (SEs). Staphylococcal enterotoxins are mainly produced by S. aureus which is enterotoxigenic strains of coagulase and Thermo nuclease (TNase) positive staphylococci. Staphylococcal enterotoxins Staphylococcal enterotoxins (SEs) are water-soluble, structurally stable, secreted polypeptides There are 17 enterotoxins (A–E, G–P) Type A is most common to cause food poisoning Serotype-F does not cause food poisoning; but causes toxic shock syndrome. The enterotoxins are heat stable can survive up to 30 minutes of boiling, resistant to drying, freezing and resistant to the action of gut enzymes. Important causes of food poisoning, enterotoxins are produced when S. aureus grows in carbohydrate and protein foods.  Epidemiology and transmission For staphylococcal food poisoning to occur following the ingestion of a given food, two conditions are necessary. First, S. aureus has to be present in the food; Second, foods stored at incorrect temperatures and time allow growth of this pathogen and the production of enterotoxin. Although S. aureus can be found in food-producing animals and raw foods, humans are considered the main reservoir for this pathogen. About 25% of people and animals have Staph on their skin and in their nose. It usually does not cause illness in healthy people, but Staph has the ability to make toxins that can cause food poisoning. Food can become contaminated during preparation if the food handler is a carrier of S.aureus and this is transferred to the food through direct contact with contaminated skin or by coughing and sneezing. The growth of S. aureus in food to a sufficient level as to allow enterotoxin production is possible only under certain conditions. For example, it needs temperatures of between 7°C and 48°C to be able to grow, with an optimum temperature of 37°C. The illness cannot be passed from one person to another If food is contaminated with Staph, the bacteria can multiply in the food and produce toxins Staph bacteria are killed by cooking, but the toxins are not destroyed and will still be able to cause illness. Food contaminated with Staph toxin may not smell bad or look spoiled. The foods that have been most frequently implicated in cases of staphylococcal food poisoning; Poultry, egg products, and cooked meat products such as ham or corned beef. Milk and milk products, canned food and bakery products. Foods that are not cooked after handling, such as sliced meats, puddings, pastries, potato salads, raw salads, ice creams, salted food products, and sandwiches. Pathogenesis Enterotoxin is expressed by nearly 50% of S. aureus strains. It is a preformed toxin (secreted in food before consumption) so that it can act rapidly. As a result, the incubation period is short (1–6 hours) Site of action: The toxin stimulates the vagus nerve and the vomiting center of the brain via the vagus nerve endings in the stomach lining and sympathetic nerves and shows a violent emetic response It also stimulates the intestinal peristaltic activity About 105 to 108 cfu/g of S. aureus and toxin concentration dose of 1µg/g is enough to cause infection. Enterotoxins also cause damage to the epithelial lining, villus distension, crypt elongation, and lymphoid hyperplasia of the intestinal cells. Staphylococcal enterotoxin is a heat stable toxin and is resistant to gastric juice Mechanism of Pathogenesis Super antigenic property of SEs stimulates a large number of T-cells as compared to other bacterial toxins. The SEs enter the blood and binds to MHC class II molecules then attach to the T-cells with the help of its T- cell receptor. T-cells proliferate producing a large amount of IL-2 and IFN-ƴ. More IFN-ƴ induces more MHC class II molecules which bind more superantigens and activates more T-cells. A high percentage of inflammatory cytokines stimulates the neuron receptors in the intestinal tract and causes diarrhea. Clinical Findings SFP symptoms appear 0.5–8 h (on average 3 h) after consumption of contaminated food The incubation period may depend on the age of the patient, with earlier onset of symptoms in children and teenagers compared to adults. Key symptoms are; Sudden start of nausea and violent vomiting, occasionally diarrhea( watery diarrhea), Abdominal pain, no or moderate fever, and shivering. The disease is usually self-limiting within 24 h. However, rare cases of fatal dehydration and electrolyte imbalances occur, with fatality rates ranging from 0.03% in the general population to 4.4% in children and the elderly Diagnosis History Clinical findings and their fast resolution Although laboratory tests can detect toxin-producing Staph in stool, vomit, and foods, these tests are usually not ordered except during an outbreak. In the suspecting a SFP outbreak due to characteristic clinical symptoms; samples of food, food handlers (nasal swabs), and patients (feces), as well as comprehensive questionnaires providing data on diseased and non-diseased persons. The enterotoxin gene profile can subsequently be determined by PCR and will, if possible, be matched to SE detection results in food. Chromatography method Liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS) is used for SEs detection. Treatment Fluid therapy and rest cure are suggested. People with severe illness may require intravenous fluids. Antibiotics are not useful in treating this illness because the toxin is not affected by antibiotics. Prevention and Protection To avoid contaminating the food with S. aureus, handle and prepare food safely. Remember to always follow these food safety tips: Use a food thermometer and cook foods to their safe minimum internal temperature. Keep hot foods hot (60°c or hotter) and cold foods cold (4°C or colder). Store cooked food in wide, shallow containers and refrigerate within 2 hours (or 1 hour if it’s hotter than 30° F outside). When reheating food, ensure that the temperature reaches at least 74°C. The following tips that are part of the four steps to food safety – clean, separate, cook, and chill Avoid cross-contamination by keeping work surfaces clean and ensuring separation between areas where raw and cooked foods are manipulated.  Wash your hands for at least 20 seconds with soap and water before, during, and after preparing food, and before eating. Do not prepare food if you are ill with diarrhea or vomiting. Wear gloves while preparing food if you have wounds or infections on your hands or wrists Ensure raw foods of animal origin are obtained following good hygienic practices, to reduce the possibility of S. aureus contamination. Food handlers should use appropriate protective clothing (e.g. gloves) and thoroughly wash hands. Food handlers with skin lesions should have them properly covered prior to handling food. If this is not possible, they should not work while handling food until the lesions have healed. Bacillus cereus BACILLUS SPECIES The genus Bacillus includes large aerobic, Gram-positive rods occurring in chains. The members of this genus are closely related but differ both phenotypically and in terms of pathogenesis. Pathogenic species possess virulence plasmids. B. anthracis, which causes anthrax, is the principal pathogen of the genus Most members of this genus are saprophytic organisms prevalent in soil, water, and air, and on vegetation (eg, B. subtilis), also widely isolated from food items such as vegetables, milk, cereals, spices, meat and poultry. B. cereus can grow in foods and cause food poisoning by producing either an enterotoxin (diarrhea) or an emetic toxin (vomiting). B. cereus may occasionally produce disease in immunocompromised humans (eg, meningitis, endocarditis, endophthalmitis, conjunctivitis, or acute gastroenteritis). Microbiology of Bacillus cereus 1.Bacillus cereus is gram-positive rod-shaped bacilli with square ends. 2.They are single rod-shaped or appear in short chains. 3.Tissue section staining may appear long and filamentous. 4.They are non-capsulated. 5.It contains spores with central spores. 6.Spores are oval (ellipsoidal) and not swelling the mother cell, blood and tissues or in aerobic culture. 7.It is 1×3-4 µm in size. 8.It is motile and flagellated with peritrichous flagella. 9.It is motile by two types of motility, swimming and swarming. 10.Endospores are able to survive long periods of exposure to air and other adverse environmental conditions. 11.It is a beta-hemolytic bacterium that causes foodborne disease. 12.Its virulence factors include cerolysin and phospholipase and not formed in the animal’ Epidemiology Bacillus cereus is isolated from soil, vegetables, milk, cereals, spices, fried rice, cooked poultry and meats, soups, and desserts. It is also found in mashed potatoes, beef stew, apples, hot chocolates sold in vending machines, and other improper food handling areas. Vegetative cells and spores are widely distributed in nature. It is opportunistic pathogens to immunocompromised patients and sometimes pathogens of man. Endospores show much greater resistance to physical and chemical agents such as heat, cold, desiccation, radiation, disinfection, antibiotics, and other toxins. B. cereus is most commonly associated with food poisoning, but the organism can also cause post-traumatic ophthalmitis, which requires rapid, aggressive management locally. Pathogenicity and Virulence factors of Bacillus cereus Gastroenteritis caused by B. cereus is mediated by one of two enterotoxins. The heat-stable, proteolysis-resistant enterotoxin causes the emetic form of the disease. It is a heat stable preformed toxin, resembling S. aureus enterotoxin The heat-labile enterotoxin causes the diarrheal form of the disease; each stimulates the adenylate cyclase–cyclic adenosine monophosphate system in intestinal epithelial cells, leading to profuse watery diarrhea.  Clinical Findings Food poisoning caused by B. cereus has two distinct forms: the emetic type, which is associated with fried rice, milk, and pasta, the diarrheal type, which is associated with meat dishes and sauces. The emetic form The emetic form is manifested by nausea, vomiting, abdominal cramps, and occasionally diarrhea and is self-limiting, with recovery occurring within 24 hours. Fever and diarrhea are generally absent. It begins 1–5 hours after ingestion of a plasmid-encoded preformed cyclic peptide (emetic toxin) in the contaminated food products. Most bacteria are killed during the initial cooking of the rice, but the heat-resistant spores survive. If the cooked rice is not refrigerated, the spores germinate, and the bacteria can multiply rapidly. The heat-stable enterotoxin that is released is not destroyed when the rice is reheated. The emetic form of the disease is an intoxication, caused by the ingestion of the enterotoxin and not the bacteria. The diarrheal form The diarrheal form of B. cereus food poisoning is a true infection, resulting from the ingestion of the bacteria in contaminated meat, vegetables, or sauces. There is a long incubation period (6-24 hours), during which the organism multiplies in the patient’s intestinal tract, and the release of the heat-labile enterotoxin follows. This enterotoxin is responsible for the profuse watery diarrhea, nausea, and abdominal cramps. Vomiting are uncommon. Laboratory Diagnosis of Bacillus cereus Specimens: faeces, vomitus, remaining food (if any), eye specimen (corneal swab) Direct detection methods 1.Microscopically the organisms appear as large gram-positive rods in singles, pairs, or serpentine with square ends after gram staining. 2.Endospores formation are seen as an unstained oval or round region within the center of the cell. Spores are oval (ellipsoidal) and not swelling of the mother cell.  SERODIAGNOSIS Serologic methods are available for the detection of B. cereus toxin in food and feces. Microslide gel diffusion test is generally used as a toxin detection system. MOLECULAR METHOD The toxigenic potential of B. cereus isolates, genes encoding emetic-toxin cereulide (ces), and enterotoxins (nhe, hbl and cytK) can be analyzed by multiplex PCR. Treatment of Bacillus cereus Persons with B. cereus food poisoning require only supportive treatment. Oral rehydration or, occasionally, intravenous fluid and electrolyte replacement for patients with severe dehydration is indicated. Antibiotics are not indicated. Patients with the invasive disease require antibiotic therapy. Bacillus cereus is susceptible to clindamycin, erythromycin, vancomycin, aminoglycosides, and tetracycline. It is resistant to penicillin and trimethoprim. Prevention and Control of Bacillus cereus Diarrheal and vomiting intoxications by this organism are readily preventable by appropriate food-handling procedures. Meat and vegetables should not be held at temperatures between 10 and 45 °C for long periods, and rice held overnight after cooking should be refrigerated and not held at room temperature. Prevention of infection in patients following surgery or in those who are immunocompromised or who are otherwise predisposed to infection depends on good practice. MUSHROOM POISONING Most of the serious complications from eating certain mushrooms are neurologic. However, nausea, abdominal pain and diarrhea can occur early on. The worst type of poisoning is that due to Amanita species (e.g. Amanita phalloides) when diarrhea and abdominal cramps occur within hours followed a day or two later by hepatorenal failure which carries a substantial mortality risk Introduction Clostridium botulinum is the causative agent of botulism. It produces dangerous neurotoxins (botulinum toxins) under low-oxygen conditions. Botulinum toxins block nerve functions and can lead to respiratory and muscular paralysis. Botulinum toxins are one of the most potent, lethal substances known to man. Clostridium botulinum Large, rod-shaped, Gram-positive, Strictly anaerobic, Motile, Forms a subterminal spore, Noncapulated Reproduces through binary fission Genome size: 3.89 Mb Spores The spores of C. botulinum are found worldwide in soil, pond, marine, and lake sediments. Easily isolated from the surfaces of vegetables, fruits, and seafood, The spores of C. botulinum are heat resistant. Spores can be destroyed by heating to 120°C for five minutes. When appropriate environmental conditions are present, the spores will germinate and grow into toxin-producing bacilli. Toxins A neurotoxin 'botulinum toxin' probably the most toxic substance known to be lethal to humankind as little as 30-100 ng potentially fatal. ( with a lethal dose of 1.3–2.1 ng/kg in humans) It is estimated that one gram of aerosolized botulism toxin could kill at least 1.5 million people.  The toxin itself has no smell or taste. If ingested, the toxin is primarily absorbed by the stomach and small intestine, although the large intestine is capable of absorbing the toxin as well. The toxin is resistant to degradation by gastric acidity and human alimentary enzymes alike. Botulinum toxin is inactivated in chlorinated water after only 20 minutes of exposure all types of botulinum toxin are rapidly destroyed by heating to 100 °C for 15 minutes). Pathogenesis Botulism and tetanus result from intoxication with the protein neurotoxins elaborated by two related species of Clostridium. The toxins are very similar in structure and function but differ in their clinical effects because they target different cells in the nervous system. Botulinum neurotoxins predominantly affect the peripheral neuromuscular junction and autonomic synapses and primarily manifest as weakness. In contrast, although tetanus toxin can affect the same systems, its effects reflect tropism for inhibitory cells of the central nervous system and primarily manifest as rigidity and spasm. Both conditions have potentially high fatality rates, and both are preventable through education and public health measures.  Once inside the neuron, the toxin binds to the presynaptic membrane of the cholinergic nerve terminals, blocking the release of the neurotransmitter acetylcholine. Acetylcholine plays an essential role in the body, as it is responsible for regulating the somatic nervous system, which controls the voluntary movements of the skeletal muscles.The botulinum endopeptidase inactivates the proteins that regulate release of acetylcholine, blocking neurotransmission at peripheral cholinergic synapses. Because acetylcholine is required for excitation of muscle, the resulting clinical presentation of botulism is a flaccid paralysis. Transmission C. botulinum strains have been isolated from all over the world C. botulinum is most commonly found in the soil and freshwater sediment. The bacteria also can live in animal intestines and be found in animal feces. The spores of the bacteria are not usually found in human feces unless the human has contracted botulism. C. botulinum is often found in improperly canned goods. Foods which cannot be heated to temperatures high enough to kill the endospores should take other precautions to prevent colonization of the Clostridium botulinum, such as maintaing a pH below 4.6 which will not harbor the bacteria. Botulism is not spread from person to person.  Toxin is produced within the canned food and ingested preformed. If spores contaminate food, they may convert to the vegetative state, multiply, and produce toxin in storage under certain conditions. This may occur with no change in food taste, color, or odor. The alkaline conditions provided by vegetables, such as green beans, and mushrooms and fish particularly support the growth of C botulinum. Because the toxin is heat-labile, in order to produce disease the food must be ingested uncooked or after insufficient cooking. Botulism often occurs in small family outbreaks in the case of home prepared foods or less often as isolated cases connected to commercial products. Infant and wound botulism result when the toxin is produced endogenously, beginning with spores that are either ingested in difficult to sterilize foods (honey) or contaminate wounds. Clinical Findings The toxin, resistant to enzymes in the gastrointestinal tract, is absorbed through the small intestine. Once absorbed, passes into the bloodstream, by which it reaches peripheral cholinergic synapses (including the neuromuscular junction. Botulism is classically described as the acute onset of bilateral cranial neuropathies associated with symmetric descending weakness. Absence of fever Symmetric neurologic deficits The patient remains responsive Normal or slow heart rate and normal blood pressure No sensory deficits, with the exception of blurred vision The time course depends on the amount of toxin present and whether it was ingested preformed in food or produced endogenously in the intestinal tract or a wound. The clinical forms Foodborne botulism, İnfant botulism, Wound botulism, Adult intestinal toxemia botulism Iatrogenic botulism. Inhalational botulism (bioterorism) Diplopia, dysphasia, dysarthria, ptosis, Descending symmetric flaccid paralysis of voluntary muscles Loss of deep tendon reflexes Mortality is 10% to 20%. Constipation There are no sensory or cognitive deficits Respiratory muscle paralysis may lead to respiratory failure and death. Infant botulism in infants between the ages of 3 weeks and 12 months. They are acquired through the ingestion of spores rather than preformed toxin. The infant’s intestinal flora is thought to be particularly permissive for the germination of spores, which leads to the production of toxin. In the absence of competing flora found in children and adults, C. botulinum colonizes the intestine of infants. Infant Botulism Infant botulism If infant botulism is related to food, such as honey, problems generally begin within 18 to 36 hours after the toxin enters the baby's body. Signs and symptoms include: Constipation (often the first sign) Floppy movements due to muscle weakness and trouble controlling the head Weak cry Irritability Drooling Drooping eyelids Tiredness Difficulty sucking or feeding Paralysis Infant botulism may mimic sudden infant death syndrome. Wound Botulism Spores are introduced into a wound, where they germinate and produce toxin. Most common in people who inject black tar heroin. Wound botulism in parenteral users of cocaine and maxillary sinus botulism in intranasal users of cocaine has been reported. Disease similar to that from food poisoning may develop, or it may begin with weakness localized to the injured extremity. Wound botulism may be caused by either type A or type B organisms. The incubation period is generally longer (4 days or more-14 days), and the gastrointestinal tract symptoms are less prominent. Iatrogenic botulism It results from the injection of an overdose of toxin while used for therapeutic purposes. Bioterrorism-associated botulism C. botulinum toxins are the most potent toxins known, and there has therefore been interest in developing them as agents of bioterrorism. Transmission of bioterrorism-associated botulism would be inhalation of aerosolized toxin, although transmission via the GI route is also a possible mode of attack It is estimated that inhalation of aerosolized botulinum toxin would result in an acute symmetric descending flaccid paralysis with prominent bulbar palsies (diplopia, dysarthria, dysphonia, and dysphagia) after 12 to 72 hours It is estimated that anaerosol release of toxin could affect 10% of people within 500 meters Mortality rates may be much higher (60%). Diagnosis Demonstration of toxin in serum, gastric secretions, stool, or food samples or by isolation of C. botulinum from stool, wound specimens, or food sources (6 days). The most sensitive means of botulism toxin detection is the mouse bioassay. Enzyme-linked immunosorbent assay has been used to detect botulinum toxin in clinical specimens as well as contaminated food samples. PCR tests are used to detect the DNA encoding the toxin. Because these confirmatory tests do not yield timely results, the decision to administer antitoxin should be based on the presumptive clinical diagnosis of botulism and not be delayed while awaiting results of confirmatory diagnostic studies.  Treatment The administration of large doses of horse C botulinum antitoxin is useful in neutralizing free toxin. The heptavalent antitoxin containing all seven types (A to G) is preferred to the trivalent antitoxin containing types A, B, and E. A bivalent antitoxin (types A and B) purified from the plasma of humans immunized with botulinum toxoid is available for the treatment of infant botulism. Intensive supportive measures, particularly mechanical ventilation, Antimicrobial agents are given only to patients with wound botulism. In infant botulism, botulism immune globulin can be used Despite aggressive management of the patient’s condition, the disease may continue to progress because the neurotoxin is irreversibly bound and inhibits the release of excitatory neurotransmitters for a prolonged period. Complete recovery in patients often requires many months to years, or until the affected nerve endings regrow. Prevention Adequate pressure cooking or autoclaving in the canning process kills spores, and heating food at 100°C for 10 minutes before eating destroys the toxin. To ensure that food is free of proteolytic botulinum, it must be treated with a temperature of at least 121 degrees Celsius for a minimum of three minutes; this process has been termed the “botulinum cook. Food from damaged cans or those that present evidence of positive inside pressure should not even be tasted because of the extreme toxicity of the C botulinum toxin.  ensure safe home and commercial canning and bottling by: using good quality and fresh produce ensuring foods are sufficiently acidic either naturally or by addition of acid (for example, lemon juice, citric acid or vinegar) ensuring foods are properly heat processed using appropriate equipment ensure proper processes in the making of fermented foods follow the manufacturer’s instructions for food storage and shelf life avoid consuming foods from damaged cans or bottles keep cold food below 5°C and hot food above 80°C. Botulinum toxin as Botox Cosmetic applications. For those that can afford it, a temporary respite from the wrinkles of aging can be gained from Botox injections administered by dermatologists and plastic surgeons. The bacteria that cause botulism are usually found where in nature? A. In feces B. In mold C. In the soil D. In the air E. On the skin An emergency call to a neighbor leads to an entire family with apparent paralysis of ocular and respiratory muscles. They had just embarked on a project of home canning and had consumed one of their own products (green beans) the evening before. It is most likely they consumed a toxin which: A. Stimulates neuromuscular synapses B. Stimulates neurotransmission in the spinal cord C. Blocks postsynaptic inhibition in the spinal cord D. Blocks acetylcholine release in the spinal cord E. Blocks acetylcholine release at neuromuscular junctions the nerve endings.