POISONOUS PRODUCTS FORMED IN FOOD BY BACTERIA AND OTHER MICRO-ORGANISMS
In close relation to the cases of infection with animal or plant
parasites which have been discussed, there are certain well-established
instances of poisoning by substances that have been generated in food
while it is still outside of the body. This is the common type of food
poisoning in popular estimation, but in point of fact the proved cases
of this class are much less frequent than the instances of true
infection with bacteria of the _paratyphoid-enteritidis_ group (chapter
vi). Thus far the best-known examples of poisoning by the products of
micro-organisms are botulism and ergotism.
ERGOTISM
Ergotism or ergot poisoning is due to the use of rye that has become
diseased through the attack of a fungus, _Claviceps purpurea_. It
occurred frequently in the Middle Ages when in times of famine the ergot
or spurred rye (O.Fr. _argot_, "a cock's spur") was often used in
default of better food. In Limoges in 922 it is said that forty thousand
persons perished from this cause. Improvement in the facilities for
transportation of food into regions where crops have failed, and the use
of special methods for separating the diseased grain from the wholesome
have greatly reduced the prevalence of ergotism. In Western Europe
poisoning from this cause has practically ceased, although Hirsch
recorded some twenty-eight outbreaks in the nineteenth century; in
parts of Russia the disease is said still to occur in years of bad
harvest.[95]
The poison ergot itself has long been used as a drug in obstetrics, but
its composition is complex and is still not completely understood.
Several constituents of ergot have been extracted, and these have been
shown to possess different physiological effects.[96] The symptoms
observed in the outbreaks of ergotism of mediaeval times are not wholly
reproduced experimentally by the drug and are thought to have been in
part due to the semi-starvation engendered by the use of rye from which
the nutritious portions had been largely removed by the growth of the
fungus.
BOTULISM
The best established case of poisoning by means of bacterial products
taken in with the food is the serious malady known somewhat
inappropriately as botulism (botulus, sausage).[97] This kind of food
poisoning, which has a characteristic set of symptoms, seems to have
been first recognized and described in 1820 by the German poet and
medical writer Justinus Kerner. In two articles (1820-22) he enumerates
174 cases with 71 deaths occurring in Wuerttemberg between 1793 and 1822
and apparently in most cases connected with the use of insufficiently
smoked sausage. Mayer[98] tabulates about 600 additional cases observed
in various parts of Germany down to the end of 1908, the total mortality
in the 800 cases being about 25 per cent. In France botulism is said to
be very rare.[99] In Great Britain Savage[100] declares that he has been
unable to trace the occurrence of a single outbreak. In the United
States several instances of botulism poisoning are on record
(Sheppard,[101] 1907, 3 cases, 3 deaths, canned pork and beans;
Peck,[102] 1910, 12 cases, 11 deaths; Wilbur and Ophuels,[103] 1914,
canned string beans, 12 cases, 1 death; Frost,[104] 1915, 3 cases, 3
deaths). Professor Stiles[105] has given a graphic description of his
own attack of probable botulism due in all likelihood to minced chicken.
[Illustration: FIG. 10.--_Claviceps purpurea:_ 1, ergot on rye-grass; 2,
ergot on rye; 3, section of a portion of the conidial form of fruit,
x300; 4, a sclerotium or ergot; 5, head of ascigerous form of fruit; 6,
an ascus, x300; 7, a single spore, x300. (After Massee, _Plant
Diseases_, by courtesy of the Macmillan Company.)]
_Symptoms._--The description of a case seen by Wilbur and Ophuels,[106]
is so typical that it may be cited:
Girl, aged 23, Tuesday evening, Nov. 23, 1913, ate the dinner
including the canned string beans of the light green color together
with a little rare roast beef. The following day she felt perfectly
normal except that at 10:00 in the evening the eyes felt strained
after some sewing. Thursday morning, thirty-six hours after the
meal, when the patient awoke, the eyes were out of focus, appetite
was not good, and she felt very tired. At night she had still no
appetite, was nauseated, and vomited the noon meal apparently
undigested. Friday morning, two and one-half days after the meal,
the eyes were worse, objects being seen double on quick movement,
and it was noticed that they had a tendency to be crossed. A
peculiar mistiness of vision was also complained of. She was in bed
until late in the afternoon, when she visited Dr. Black. She had had
some disturbance in swallowing previous to this time and stated that
it felt as if "something came up from below" that interfered with
deglutition. The fourth day she remained in bed, was much
constipated, and noticed a marked decrease in the amount of urine
voided. There was at no time pain except for occasional mild
abdominal cramps, no headache, subnormal temperature, and a normal
pulse. The fourth and fifth days the breathing became difficult at
times and swallowing was almost impossible. The patient complained
of a dry throat with annoying thirst. The sixth day there were
periods of a sense of suffocation with a vague feeling of unrest and
as if there might be difficulty in getting the next breath. The
upper lids had begun to droop. The voice was nasal. When the attempt
was made to swallow liquids they passed back through the nose. The
patient felt markedly weak.
Physical examination at this time showed ptosis of both upper
eyelids, dilatation of the right pupil, sluggish reaction to light
of both pupils, apparent paralysis of the internal rectus of the
left eye, normal retina, inability to raise the head, control
apparently having been lost of the muscles of the neck, inability to
swallow, absence of taste. The tongue was heavily coated and the
throat was covered with a viscid whitish mucus clinging to the
mucous membrane. The soft palate could be raised but was sluggish,
particularly on the right side. The exudate on the right tonsil was
so marked that it resembled somewhat a diphtheritic membrane. The
seventh day there was some change in the condition; occasional
periods occurred when swallowing was more effective, and there was
less tendency to strangle. On the eleventh day there was some
improvement of the eyes, still strangling on swallowing, sensation
of taste was keener, and the general condition improved. The twelfth
day the patient was able to move her head, but was unable to lift it
except when she took hold of the braids of her hair, and pulled the
head forward. The eyes could be opened slightly, speech was less
nasal and more distinct, and improvement in swallowing was marked.
At the end of two weeks the patient was able to take soft diet
freely, and at four weeks she was up in a chair for a couple of
hours complaining only of general weakness and inability to use her
eyes. At the end of five weeks she was able to leave the hospital
and return to her home and later to resume her regular work.
In all cases the nervous system is strikingly affected in this form of
food poisoning. Dizziness, double vision, difficulty in chewing and
swallowing, and other symptoms of nervous involvement occur with varying
intensity and may persist for a long time after the first signs of the
attack. Temperature, pulse, and respiration remain practically normal.
In contrast with the traditional type of food poisoning
gastro-intestinal symptoms may be slight or altogether lacking. Freedom
from abdominal pain is usually noted; diarrhea is the exception and
constipation the rule; vomiting sometimes occurs, but may be absent. In
the cases described by Sheppard there was "an entire absence of the
usual gastro-intestinal symptoms from first to last, no pain or sensory
disturbance and no elevation of temperature." The visual disturbances
are very characteristic. Stiles relates his own experiences as follows:
Vertigo and nystagmus developed [a few hours after eating] in a
startling degree, the car [in which he was being taken to his house]
seemed to be ascending an endless spiral, the stars made circles in
the sky, and the houses by the wayside reeled. The lighted doorway
of my house seemed to approach and surround me as I was carried in.
My bed for the moment presented itself as a vertical surface which I
could not conceive to be a resting place.... Whenever I opened my
eyes on this day [the next day] the impression of gyration of the
room was appalling.... To turn my head even very slowly from one
side to the other brought an accession of the overpowering
giddiness.... [eight days after the beginning of the attack]. The
nystagmus now became limited to momentary onsets, but in its place I
became aware of a peculiar diplopia. The image of one retina was not
merely displaced from the position of its fellow but was tilted
about 15 degrees from parallel.... This fantastic diplopia gradually
gave place to the familiar variety and this occurred less and less
often as my convalescence proceeded. From [this date] my recovery
pursued a course which was dishearteningly slow but free from any
setbacks. Among the persistent symptoms were ... the visual
difficulties mentioned. The left pupil was usually smaller than the
right and I thought I detected a slight failure to relax
accommodation with the left eye. Reading was difficult for several
weeks and the ability to write, as requiring closer fixation, was
still longer in returning.
In the cases reported by Sheppard visual symptoms were the initial signs
of trouble, double vision, mistiness, and inability to hit the mark in
shooting being the first complaint.
The time elapsing between eating the implicated food and the onset of
the earliest symptoms is usually between twelve and forty-eight hours,
but may be much less. In Stiles's case the interval was apparently less
than three hours.
_Anatomical lesions._--In fatal cases no characteristic gross changes
are observed in the various organs. It has been stated by some writers
that microscopic degenerative changes occur in the ganglion cells,
involving especially the so-called Nissl granules, but in the carefully
studied case reported by Ophuels[107] the Nissl granules were quite
normal in size, arrangement, and staining qualities. There was, in fact,
no evidence to substantiate the hypothesis of a specific action of the
toxin on the nerve-cells. On the other hand, Ophuels found numerous
hemorrhages in the brain-stem and multiple thromboses in both the
arteries and veins. He holds, consequently, that the indications of
severe disturbances of brain circulation associated with hemorrhages and
thrombosis in medulla and pons are sufficient to explain the symptoms of
botulism poisoning without having recourse to the assumption that the
poison has a specific action on certain ganglion cells.
_Bacteriology._--The cause of botulism poisoning was discovered by Van
Ermengem to be the toxin produced by a bacillus which he named _B.
botulinus_. This organism was isolated from portions of a ham that had
caused fifty cases of poisoning (1895) at Ellezelles (Belgium), and also
from the spleen and gastric contents of one of the three fatal cases.
The bacillus grows only in the absence of oxygen (strict anaerobe),
stains by Gram's method, forms terminal spores, and develops best at
22 deg.C. Unlike most bacteria dangerous to man, it appears unable to grow
in the human body, and its injurious effect is limited to the action of
the toxin produced in foodstuffs outside the body. Botulism is an
intoxication--not an infection. The fact that the bacillus can grow in
nature only when the free oxygen supply is cut off explains in part at
least the relatively rare occurrence of botulism since all the
conditions necessary for the production of the botulism toxin do not
commonly concur. Next to nothing is known as to how widely _B.
botulinus_ is distributed. Except in connection with the cases of
poisoning it has been reported but once in nature.[108] The botulism
poison is a true bacterial toxin, chemically unstable, destroyed by
heating at 80 deg.C. for 30 minutes, capable of provoking violent symptoms
in minute doses, and possessing the property characteristic of all true
toxins of generating an antitoxin when injected in small, non-fatal
doses into the bodies of susceptible animals. In animal experiments the
toxin formed by _B. botulinus_ has been found capable of reproducing the
typical clinical picture of this form of food poisoning. Symptoms of
paralysis are produced in rabbits, guinea-pigs, and other animals by the
injection of so small a dose as 0.0001 c.c. of a filtered broth culture.
[Illustration: FIG. 11.--_Bacillus botulinus_ with spores. Pure culture
on sugar-gelatin. Van Ermengem preparation. (Kolle and Wassermann.)]
_Epidemiology._--The conditions under which _B. botulinus_ occurs and is
given opportunities for multiplying are not completely known. It is
possible that there are localities where this bacillus is particularly
abundant in the soil or in the intestinal contents of swine or other
domestic animals, but on the whole it seems more probable that the
organism is widely distributed, but that it does not often find suitable
conditions for entrance into, and multiplication in, human food.
Practically all the reported cases of botulism have been caused by food
which has been given some sort of preliminary treatment, as smoking,
pickling, or canning, then allowed to stand for a time, and _eaten
before cooking_. Since both the bacillus, including the spore stage, and
its toxin are destroyed by relatively slight heating, it is clear that a
rather unusual set of factors must co-operate in order that botulism
poisoning shall take place. These are evidently: (1) the presence of the
bacilli in sufficient numbers in a suitable foodstuff; (2) the initial
preparation of the food by a method that does not destroy the _B.
botulinus_--inadequate smoking, too weak brine,[109] or insufficient
cooking; (3) the holding of this inadequately preserved food for a
sufficient length of time under the right conditions of temperature and
lack of oxygen; (4) the use of this food, in which conditions have
conspired to favor the production of toxin by _B. botulinus_, without
final adequate cooking. It seems as reasonable to suppose that the
infrequency with which these several factors coincide is responsible for
the relative uncommonness of botulism as to suppose it due to the rarity
of the specific bacillus. In the Belgian outbreak studied by Van
Ermengem the poisonous ham had lain at the bottom of a cask of brine
(anaerobic conditions) while the other ham of the same animal lay on top
of it but was not covered with brine, and was eaten without producing
any poisonous effect. In this instance the presence or absence of
favorable conditions for anaerobic growth seemed to be the decisive
factor.
_Prevention and treatment._--The food in which _B. botulinus_ has grown
does not seem to be altered in a way that necessarily arouses
suspicion. In the case described by Roemer the incriminated ham showed
bluish-gray areas from which _B. botulinus_ could be isolated, but this
condition does not seem to have attracted attention before the poisoning
occurred and was an observation made only after the event. So far as can
be learned the meat that has caused botulism has always come from
perfectly sound animals. In some cases the accused article of food is
said to have had a rancid or acrid taste (due to butyric acid?), but
there is nothing definitely characteristic about this, as the majority
of anaerobes produce butyric acid. If, as in the Darmstadt[110] and
Stanford University[111] epidemics, the food (canned beans) is served
with salad dressing, a sour taste might pass without notice or even add
to the relish. In the instance reported by Sheppard the canned beans
were good in appearance, taste, and smell.
The obvious precaution to take against poisoning of this sort is first
the use of adequate methods of food preservation. To judge from the
recorded outbreaks, domestically prepared vegetables and meats are more
likely to give rise to botulism than those prepared commercially on a
large scale. The general use of steam under pressure in the large
canning factories affords a high degree of protection against the
anaerobic bacteria and their resistant spores. Whatever the method of
treatment, all canned or preserved food having an unnatural appearance,
taste, or odor should be rejected. Reheating of all prepared foods
immediately before use is an additional safeguard. Foods, such as
salads, composed wholly or in part of uncooked materials should not be
allowed to stand overnight before being served.
If symptoms of botulism, such as visual disturbances, become manifest,
the stomach should be emptied with a stomach pump, cathartics
administered, and strychnine and other stimulants given as required.
Since one of the noteworthy features of this disease is the paralysis of
the intestinal tract by the toxin absorbed, the guilty food may lie for
a long time in the stomach (cf. Stiles, _loc. cit._). Consequently,
measures to empty the stomach should be taken even if the patient does
not come under observation until several days after the poisonous food
has been eaten.
An antitoxic serum has been prepared at the Koch Institute in Berlin.
This serum has given successful results in animal experimentation, but
has not been used, so far as I can learn, in any human outbreak. It is
not available at any point in this country.
OTHER BACTERIAL POISONS
The interesting case reported by Barber[112] shows that there are other
possibilities of food poisoning by formed bacterial poisons. Acute
attacks of gastro-enteritis were produced in several individuals by the
use of milk containing a poisonous substance elaborated by a white
staphylococcus. This staphylococcus occurred in almost pure culture in
the udder of the cow from which the milk was derived. The milk when used
fresh was harmless and the poison was generated in effective quantities
only when the milk stood some hours at room temperature before being
used. The symptoms were similar to those usually ascribed to "ptomain
poisoning."
SPOILED AND DECOMPOSED FOOD
There is a general belief that food is unwholesome whenever the evidence
of the senses shows it to be more or less decomposed. This opinion finds
expression in civilized countries in many legal enactments forbidding
traffic in decomposed meats, vegetables, and fruits. There is
unfortunately lack of evidence as to what kinds or degree of visible
decomposition are most dangerous. In fact, some foods of high nutrient
value, notably cheeses, are eaten only after somewhat extensive
decomposition processes (termed ripening) have taken place. The
characteristic flavors or aromas of the various hard and soft cheeses
are due to the substances formed by certain species of molds and
bacteria and are just as properly to be regarded as decomposition
products as the unpleasant stenches generated by decomposing eggs or
meat. Indeed, some of the decomposition products formed in the ripening
of Brie, Camembert, or Limburger are similar to, if not identical with,
those which are associated with spoiled foods. Sour milk, again, is
recommended and commonly used as a food or beverage for persons in
delicate health, and yet sour milk contains many millions of bacteria
and their decomposition products. Some of the bacteria commonly
concerned in the natural souring of milk are closely related to
pathogenic types. The partial decomposition of meats and game birds is
often considered to be advantageous rather than otherwise. Even eggs, a
food whose "freshness" is marred for most persons by the initial stages
of decomposition, are ripened in various ways by the Chinese and eaten
as a delicacy after the lapse of months or years. The preserved ducks'
eggs known as pidan are stored for months in a pasty mixture of tea,
lime, salt, and wood ashes. "They are very different from fresh eggs.
The somewhat darkened shell has numerous dark green dots on the inner
membrane. Both the white and yolk are coagulated; the white is brown,
more or less like coffee jelly...."[113] Increase of ammoniacal nitrogen
has taken place to an extraordinary degree in these eggs, indicating
much decomposition of the egg protein. The ammoniacal nitrogen in pidan
is considerably higher than in the eggs known by egg candlers as black
rots.
It is evident, therefore, that bacterial growth in substances used as
food is not necessarily injurious and may in some cases increase the
palatability of food without destroying its wholesomeness. Little or
nothing is known about the correlation of visible signs of decomposition
with the presence of poisonous products, and it is at present impossible
to say at what point in the process of decomposition a food becomes
unfit to use owing to the accumulation of poisonous substances within
it. There seems to be no connection between the natural repugnance to
the use of a food and its unwholesomeness. Under ordinary conditions the
nauseous character of very stale eggs is proverbial, and yet few
nitrogenous foods have so clear a health record as eggs or have been so
infrequently connected with food poisoning outbreaks.
It might seem tempting to conclude on the basis of the available
evidence that spoiled or decomposed foods possess poisonous qualities
only when certain specific bacteria, like the _B. botulinus_ already
discussed, have accidentally invaded them and formed definite and
specific poisons. But we have no right to assume that the everyday
decomposition products of the banal bacteria are in all cases without
injurious effects. Even though no sharply defined acute form of
poisoning may be laid at their door, it does not follow that an
irritating or perhaps slightly toxic action of the ordinary
decomposition products is altogether absent. Our present knowledge of
the nature and degree of danger to be apprehended from the use of
spoiled food is imperfect and unsatisfactory. That fact, however, does
not release us from the obligation to continue measures of protection
based even to a limited extent on experience.
FOOTNOTES:
[95] Another species of _Claviceps_ (_C. paspali_) which attacks the
seeds of a wild grass is believed to be responsible for certain
outbreaks of poisoning among cattle and horses (_Science_, XLIII [1916],
894).
[96] Barger (_Jour. Chem. Soc._, XCV [1909], 1123) has shown that
parahydroxyphenylethylamine is present in ergot and is in some degree
responsible for the physiological action of the drug.
[97] Although some of the early outbreaks were traced to the use of
sausage, particularly in Wuerttemberg, the proportion of recent botulism
poisoning attributed to this food is no greater than of sausage-conveyed
infections with the paratyphoid bacillus (chap. vi), and a number of the
most completely studied outbreaks of botulism have been traced to ham,
beans, and other foods.
[98] _Deutsche Viertelj. f. oeffentl. Ges._, XLV (1913), 8.
[99] E. Sacquepee, _Progres med._, XXVI (1910), 583.
[100] _Report to Local Govt. Board on Bacterial Food Poisoning and Food
Inspection_, N.S. No. 77, 1913, p. 27.
[101] _Southern Cal. Pract._, XXII (1907), 370.
[102] _Ibid._, XXV (1910), 121.
[103] _Arch. of Int. Med._, XIV (1914), 589.
[104] _Amer. Med._, X (1915), 85.
[105] _Jour. Amer. Med. Assoc._, LXI (1913), 2301.
[106] _Loc. cit._
[107] _Loc. cit._
[108] In the feces of a healthy pig (Kempner and Pollock, _Deutsche med.
Wchnschr._, XXIII [1897], 505).
[109] _B. botulinus_ does not develop in media containing over 6 per
cent of salt and should not be able to grow in meat properly covered in
brine made with 10 per cent of salt (Roemer, _Centralbl. f. Bakt._, XXVII
[1900], 857).
[110] G. Landmann, _Hyg. Rundschau_, XIV (1904), 449.
[111] Wilbur and Ophuels, _Arch. of Int. Med._, XIV (1914), 589.
[112] _Phil. Jour. of Science_, IX (1914), B6, p. 515.
[113] K. Blunt and C. C. Wang, _Jour. Biol. Chem._, XXVIII (1916), 125.