Botulism

BOTULISM (from the Latin botulus—sausage), or a l l a n t i a s i s, is caused by poisoning with so-called canned, sausage, or fish toxin and manifests as neuroparalytic suffering, expressed in the disturbance of salivary gland secretion, paresis and paralysis of the eye muscles, paralysis of the intestine, paralysis of the swallowing muscles, and sometimes paralysis of the facial and hypoglossal nerves and the diaphragm. The symptoms of these lesions are: disturbance of accommodation, double vision, dilation and lack of reaction of the pupils, ptosis, dryness in the mouth and throat, difficulty or impossibility of swallowing, aphonia, slowing of respiration, constipation, and very sharply expressed weakness. All these phenomena develop gradually, after an incubation period of 16 to 36 hours from the time of consuming the spoiled food. Sometimes, before the appearance of symptoms of botulism, nausea, vomiting, and diarrhea are observed, which can be considered the result of irritation of the intestine by the spoiled food. These phenomena may already disappear by the end of the incubation period. The disease begins with the appearance of general weakness, depression, and pain in the stomach region. Appetite is lost, nausea and vomiting appear, sharp pains in the intestine, sometimes accompanied by bloating; in rare cases, diarrhea. To all this is added belching, a sensation of dryness in the throat, and heaviness of the head, reaching such intensity in some that patients use their hands to change the position of their head. On the second or third day, dizziness, unsteadiness of gait, dilation of the pupils, and difficulty in breathing appear; if there was diarrhea, it is replaced by sharp constipation. Disturbance of accommodation manifests as blurred and double vision. On the third or fourth day, ptosis appears, the pupils are dilated and do not react to light, and difficulty in swallowing and speech is noted. Due to the accumulation of viscous mucus in the trachea and larynx, a barking cough of a croupous character occurs. From the fourth to the tenth day, in the majority of cases, the speech disorder turns into complete aphonia. All secretory activity, with the exception of the excretion of urine and milk, is suppressed to a sharp degree. The ability to see gradually disappears completely. In cases of severe poisoning, muscular weakness increases greatly, respiratory movements become difficult, dyspnea turns into apnea, and death ensues. A characteristic manifestation of the toxin's action is the delay of secretion and paralysis. As a rule, the skin is dry, wrinkled, and rough. The dryness of the mucous membranes extends to the entire digestive tract. A large amount of viscous mucus accumulates in the mouth, tightly covering the tongue, which hinders its movement. Due to the disorder of swallowing, this mucus flows out of the mouth. Mobility in all parts of the intestine is sharply reduced. Sometimes after death, remnants of eaten food can be found in the stomach and the presence of toxin can be proven in it. Paralysis of the intestinal walls causes its complete obstruction. Sometimes incontinence of urine can be observed. The disturbance of respiratory movements depends on partial paralysis of the respiratory muscles, which causes breathing to become shallow and irregular. Death occurs from paralysis of the respiratory nerves as a result of degeneration of the bulbar centers. Complete paralysis of the voluntary musculature is rare, but the disturbance of its normal function is usual. Earlier authors indicate that in botulism the pulse is slow, similar to how it is in digitalis poisoning (50–60 beats per minute). However, newer authors who have observed a number of recent epidemics in America consider that a pulse over 100 (sometimes up to 150) beats per minute is a constant symptom. In uncomplicated cases, the temperature is often below normal. The combination of subnormal temperature and a frequent pulse is an important diagnostic sign. In cases of elevated temperature, one must suspect a complication of bronchopneumonia, which often joins the primary suffering and in many cases is the direct cause of death. Sensitivity is preserved almost completely. Sometimes a certain decrease in sensitivity at the fingertips is observed. Abdominal pain and headache, which were present at the beginning of the disease, are absent at the height of the disease. Consciousness does not leave the patient until death. The duration of the disease and the severity of symptoms vary widely. They depend on the amount of toxin that has entered the intestine, the speed of its absorption, and a number of other poorly clarified conditions. The disease can manifest both in a very innocent form of rapidly passing poisoning and in a form of poisoning in which all symptoms develop violently and lead to death in a very short time. Usually, death occurs within the first 10 days. According to a number of authors, patients who survive 10 days recover in the majority of cases. In severe cases of botulism, recovery is very slow and gradual. Weakness of the voluntary musculature of the body, paresis, and paralysis of the eye muscles remain for months. Pathological anatomical changes are not specific. The vessels of the intestine are injected, dark red in color; the liver and spleen are enlarged. The urinary and gallbladder are distended and full. The lungs are hyperemic, with petechial hemorrhages. Sometimes fibrinous meningitis is observed. The intestinal mucosa is edematous, flaccid; desquamation of the epithelium is observed in it. Microscopically—parenchymatous and fatty degeneration of the liver and kidneys, mucous degeneration of the salivary glands. Necroses and hemorrhages in the anterior horns of the spinal cord and bulbar centers. Degenerative changes in the ganglion cells have also been described. Treatment of botulism is symptomatic: gastric lavage, cleansing of the intestine (not calomel!), animal charcoal internally. At the present time, specific therapy with antitoxic sera is widely used. Botulism should be considered not as an infectious disease, but as poisoning by a preformed microbial toxin produced outside the organism. This toxin is formed in various kinds of canned goods by a special microbe (Clostridium botulinum van Ermengem), which was first isolated and studied by van Ermengem in 1898. At the present time, this name is understood to mean a whole series, a group of microbes, very close in their morphological, biochemical characteristics, and in the physiological action of their toxins. They differ from each other by the property of their toxins to be neutralized by strictly homologous antitoxic sera. Three well-differentiated types of Cl. bot. are known: A, B, and C, the toxins of which, upon immunization of animals with them, give sharply specific antitoxic sera. Types A and B are encountered more often. Cl. bot. is a large, thick rod, 0.8 to 1.2 μ in width and 4 to 6 μ in length, sometimes with rounded ends, weakly motile. Motility depends on the presence of flagella, 6–8 in number, arranged peritrichously. It is encountered either as individual rods or in short chains. It stains well with all aniline dyes and by Gram (but is easily decolorized by Gram). It forms spores; the spores are oval, usually located at the ends of the rod, but can also be located closer to the middle. It is a strict anaerobe. The temperature optimum is at 22–25°, the pH optimum is 7.4. It liquefies gelatin and coagulated blood serum. Not all types decompose the latter equally—type C is the most active. Types A and B decompose the following carbohydrates: glucose, levulose, maltose, dextrin, glycerin, and salicin; they do not decompose galactose, sucrose, lactose, raffinose, inulin, adonitol, dulcitol, mannitol, xylose, arabinose, rhamnose, and inositol. Type C decomposes, in addition to those indicated, galactose and inositol and does not decompose salicin. Sugars are decomposed with the formation of acid and gas. Cultures emit the odor of butyric acid. In relation to the agglutination reaction, 7 groups are distinguished: three belong to type A and four to type B. The spores of the microbe are distinguished by exceptional resistance to various kinds of chemical and physical influences. Of the common disinfectant agents, a 10% solution of carbolic acid kills them within an hour, and formalin in 24 hours. In media containing over 6% NaCl, the spores do not develop. Dried spores are especially resistant. They withstand heating at 100° for up to 360 minutes, at 105°—up to 120 minutes, at 120°—up to 10 minutes. The spores of type A are the most resistant. Different resistance of spores in different strains is also observed. The most characteristic feature of Cl. bot. is its ability to produce a toxin of very great strength. It has been possible to obtain a toxin containing up to 500,000 lethal doses for a guinea pig weighing 300–400 g in 1 cubic cm of filtrate of a broth culture. The toxin of greatest strength is obtained on broth with 1% glucose, the pH of which is 7.4, when grown for 4 to 7 days. A peculiarity of the toxin, distinguishing it from other bacterial poisons, is its ability to act when introduced through the mouth. All animals are sensitive to the botulism toxin. The only animal on which the toxin, introduced through the mouth, does not act is the mouse. The action of the toxin is similar to the action of curare. Paralytic phenomena dominate: the muscles are flaccid and soft, the animal is in a state of complete prostration, and due to paralysis of the swallowing muscles, viscous saliva flows from the mouth and nose. Death occurs from paralysis of the bulbar centers no earlier than 34 hours after injection. Macroscopically, no sharply expressed pathological anatomical changes are observed during autopsy. Sometimes, at the site of injection, slight edema and hemorrhage can be observed.

The intestines are injected, the liver and spleen are enlarged and dark red in color; the bladder is distended; there are punctate hemorrhages in the lungs. Microscopic examination reveals extremely severe degeneration of the nerve cells of the nuclei of the pons varolii, the medulla oblongata, and the anterior horns of the spinal cord. The toxin is unstable, weakens rapidly upon exposure to air and light; it is completely destroyed by heating for 15-20 minutes at 80°. Upon prolonged storage or upon 14-18 days of combined action of formalin (4‰-5‰) and high temperature (39-40°) on it, the toxin loses its toxicity, turning into a toxoid (see Anatoxin), but retaining, however, the ability to immunize. Experiments on the use of anatoxin for the purpose of immunizing animals by mouth were carried out by Weinberg with positive results on rabbits and by Betz on guinea pigs. Immunized animals tolerated from 5 lethal doses (rabbits) to 50 (guinea pigs). When immunizing animals with toxin, antitoxic sera are obtained, which possess species specificity. These sera are used for therapeutic purposes. The pathogenicity of the microbe for animals is not great. In order to cause the multiplication of spores inside the organism, it is necessary to introduce them in a very large quantity. Spores can remain inside the organism for a long time without germinating and without poisoning the animal. The microbe is very widely distributed in nature. It can be considered a common inhabitant of the soil, from which it was possible to isolate it in 70% of the tested samples. It is found in dust, in the silt of bodies of water, and on the surface of various kinds of vegetables and fruits. On fruits and vegetables, it was possible to find it in 30% of studies. The microbe is especially often encountered on rotting fruits. It was often found in the intestinal contents of a patient with botulism and of a normal person, horses, cows, and especially pigs, in the intestinal contents of fish from the Cyprinidae family. Such a wide distribution of the microbe in nature fully explains the possibility of it getting into various food products. The presence of botulinum toxin is possible in all types of canned goods, both vegetable and meat. Cases of poisoning by fresh, smoked, and dried fish have been described, especially from the sturgeon family (the so-called red fish). Sturgeon feed on fish, possibly from the Cyprinidae family, the presence of Cl. botulinum in the intestines of which has been proven. This may explain the frequent entry of the microbe into canned goods made from these fish. Poisonings by ham, sausage, lobsters, shrimp, various kinds of compotes, and canned vegetables and fruits have been described. Canned peas and compotes made from apricots and peaches enjoy the worst reputation in America. Poisonings have never been observed when consuming canned goods covered with olive or other oil (sardines, sprats). Isolation of the microbe for diagnostic purposes is quite difficult, especially if parts of the canned goods that caused the poisoning are sent for examination, e.g., pieces of balyk, ham, sausage. They may contain neither the microbe nor the toxin, or only the toxin, which has penetrated here from neighboring areas where the microbes were developing. The following are subject to examination: 1) remnants of food that served as the source of poisoning; 2) during autopsy of a corpse, pieces of the small and large intestines, contents of the stomach, if found; 3) vomitus and stomach contents obtained during lavage. The analysis is conducted in two directions: obtaining a culture of the microbe and establishing the presence of its toxin. To isolate the microbe, it is best to use blood sugar plates containing 1% glucose and 5% defibrinated blood. To determine the presence of toxin, a ground emulsion of the suspicious material is injected into animals (mice, guinea pigs). The developing picture of botulism indicates the presence of poison. Since botulinum toxins are not uniform, homologous antitoxic serum must be used for therapeutic purposes, for which it is necessary to establish not only the presence of poison in general, but also to determine to which type this poison belongs. For this purpose, the following experiment is used, which is conducted on mice and guinea pigs simultaneously. The suspicious material is ground in a mortar with physiological NaCl solution and divided into four parts. One part of the material is mixed with immune botulinus A serum, another with the same amount of serum of type B, and the mixture is left to stand for half an hour to three hours, after which it is injected into animals in such a way that the mice receive 0.5 cubic cm of the test material and 100 antitoxic units of serum, and the guinea pigs receive 1 cubic cm of material and 300 antitoxic units. The third part, heated at 100° for half an hour, and the fourth, not heated, are injected in the same amounts into control guinea pigs and mice. The type of toxin is determined by the protective effect of the immune serum. Animals that do not die will show that the serum used in this case neutralized the toxin and, therefore, should be used for therapeutic purposes. Death of animals from the heated material will indicate the presence of other poisonous substances. Cases of poisoning by canned poison occur sporadically everywhere. In those countries where the consumption of all kinds of canned products is especially widespread, small epidemic outbreaks are often observed, usually limited to a small circle of people. Thus, in the U.S.A. in 1918 and 1925, 13 such epidemics per year were observed, in 1922—22 epidemics. In total, since the discovery of the microbe, from 1899 to 1926, 147 epidemics were observed, covering over 500 people, of whom 337 died. In Prussia, for the period from 1898 to 1919, 223 cases of the disease were observed, of which 27 ended in death. In our country, in areas where canned products (dried and smoked fish) are widely used, e.g., in Astrakhan, on the Don, etc., cases of botulism are also often observed. Spontaneous cases of botulism also occur in animals when consuming contaminated feed. In horses, this disease in Germany is known as Borna disease, and in France—as acute cerebrospinal meningitis. Poisonings by fodder have been observed in donkeys, bulls, goats, and others. Chicken disease (“wry neck”) is also caused by the consumption of feed contaminated with botulinus. Prevention of botulism. The wide distribution of the microbe in nature and the extraordinary resistance of its spores fully explain the possibility of them getting into various kinds of canned products. The favorable conditions created in the depths of the canned goods for the germination of spores (presence of abundant nutrient material and anaerobic conditions) provide the opportunity for the formation and accumulation of toxin. The resistance of spores to heating has great practical significance in the manufacture of canned goods; neither a single boiling for several minutes, nor repeated triple boiling for 15 to 60 minutes, nor even ten-minute heating in an autoclave at 120° kills the spores, but only delays their development; during prolonged storage of canned goods, the spores normally germinate, and toxin accumulates. Therefore, for the purpose of preventing botulism, all suspicious, long-stored canned goods should be boiled for 30-45 minutes before consumption in order to destroy the toxin accumulated there. Poisonings are caused only by the toxin; the presence of live spores, free from toxin, cannot cause the disease. There are no sharply striking signs of contamination of products with Cl. botulinum. Therefore, all products possessing a sharp odor of butyric acid (smell of rancid butter or old rancid cheese) should be considered suspicious for the presence of Cl. botulinum; the presence of gas bubbles, swelling of tin cans, and mold are also characteristic. When consuming suspicious products, it is necessary to keep in mind the following: 1. When heating canned goods containing gas, the impression of boiling is obtained before the boiling temperature is reached. Therefore, it is recommended to boil longer, as indicated above, to heat the entire thickness of the canned goods equally. 2. Suspicious products that have been subjected to boiling for 10 minutes or heated for an hour at 80° are not safe for consumption; poisonings have been observed when consuming such insufficiently heated products. 3. When manufacturing various kinds of canned goods, one should remember the resistance of Cl. botulinum spores to high temperatures and heat them under pressure at a temperature of 120-130° for at least half an hour. 4. The important fact that spores do not germinate in brines containing at least 6% NaCl explains to us the low frequency of botulism, since usually brines for all kinds of pickling rarely contain less than 10% NaCl. Hence the practical conclusion for salting—use brines containing at least 9-10% NaCl. In addition to the indicated measures, prevention of botulism is also possible through active immunization with non-toxic derivatives of the toxin—toxoids (anatoxins) or, following the example of active immunization for diphtheria and tetanus, with a mixture of toxin and antitoxic serum.