the manufacturers. On July 27, 1907, while the material was yet
fresh, three young Norway rats were caught and kept confined in a
large wire rat trap. Beginning with the date given, and for a period
of forty days thereafter, azoa was fed to the rats at intervals of a
few days until ten 75-cent bottles had been consumed. The rats ate
the cracked grain with which the virus was mixed very readily, and
other food was denied them each time the azoa was given until every
particle was eaten. At the end of the forty days the rats were still
apparently in a healthy condition, and were removed from the trap
and killed with a club.
Thompson,[BC] 1906, states that three laboratory attempts have been
made to destroy rats with imported strains of Danysz rat virus without
success. Danysz having arrived at Sydney to study a similar method of
destroying rabbits, the opportunity was taken of making a further
attempt under his supervision with virus which had been imported and
subsequently increased to the requisite degree of virulence, and had
been placed at Thompson’s disposition. The grounds of the Gladesville
Asylum, a large institute for the insane, were chosen for the tests,
which were conducted by Dr. R. J. Millard.
Footnote BC:
Thompson, J. Ashburton: Report of the Board of Health on plague in
New South Wales, 1906. On a sixth outbreak of plague at Sydney,
1906. Legislative assembly, N. S. W., 1907.
Millard summarized his result by stating that they can not be
considered a satisfactory demonstration of the efficacy claimed for
the Danysz virus. The results indicate a rapid loss of virulence,
which must be obviated if this virus is to be of utility for rat
destruction.
Again, in 1907, during the seventh outbreak of plague in Sydney,
Thompson[BD] had Millard test the preparations known as azoa and
ratin. The laboratory results with these preparations were similar to
those made by other investigators. Experiments made upon the ship
_Hartfield_ with azoa produced no considerable epizootic. The fatality
among such rats as were infected was small. The practical tests with
azoa upon several areas along the harbor front also resulted in
disappointment.
Footnote BD:
Thompson, J. Ashburton: Report of the board of health on plague in
New South Wales, 1907. On a seventh outbreak of plague at Sydney,
1907. Legislative Assembly, N. S. W., 1908.
The tests made with ratin upon the bark _Quilpe_ produced no epizootic
among the rats, and of the rats caught none of them showed infection;
and the field experiment at Gladesville also resulted negatively so
far as dead or sick rats were concerned. Nevertheless, there was
apparently considerable diminution in the rat population of this area.
Foster,[BE] 1908, reports unfavorably upon the results of tests made
of some of these rat viruses. Laboratories were opened for the use of
different parties who wished to make tests. The tests were conducted
under their own supervision. The rats which were not fed on anything
but grain died as freely as those that had been fed on azoa. So far as
this preparation is concerned Foster states that it is absolutely
useless to depend upon it.
Footnote BE:
Foster, N. K.: The danger of a general plague infection in the
United States. Proc. Confer. State and Prov. Boards of Health of N.
America, 1908, p. 15.
Several reports are found in print in which the rat virus was laid out
in certain localities and shortly afterwards the rats disappeared—at
least no more were noticed. Such observations are apt to be
misleading, for rats are migratory. They come and go, especially when
disturbed. Further, it is doubtful, as far as plague is concerned,
whether it is desirable to drive the rats away, for they may thus
scatter the infection.
S. S. Mereshkowsky and E. Sarin[BF] have recently studied ratin II,
put out by a Copenhagen firm—“Bakteriologisches Laboratorium Ratin.”
The label upon the can of ratin II states that it is a bacterial
culture, which produces in rats an infectious and fatal disease,
killing them in two to eight days. The samples used by the authors
were obtained as needed from the St. Petersburg representative of the
firm. Feeding experiments carried out with gray rats (_Mus decumanus_)
showed that the rapidity and severity of the symptoms was proportional
to the amount ingested. No positive results were obtained from the
bacteriological examination of the bodies.
Footnote BF:
Ueber das Ratin II. Centralb. für Bakt. Parstk. u. Infectsk.
Originale. Bd. 51. Heft 1. July 17, 1909, p. 6.
The ratin itself was sometimes found to be sterile, sometimes found to
contain several varieties of bacteria and fungi, but no one variety
was constantly present.
The potency of the ratin was not altered by exposure to 100° C. for
one hour or 120° C. for five minutes. It was destroyed, however, by
burning to an ash.
Identical poisonous results were obtained upon rats by feeding them
with “Scilla maritina cum bulbo rubro.”
Microscopical examination disclosed a small portion of a lamella,
identified as belonging to the Liliaciæ, to which family squill
belongs.
The authors conclude that ratin II is not a bacterial culture, but a
poison rendered more dangerous to persons and domestic animals by the
misleading statements of its makers.
PATHOGENICITY FOR MAN.
Loeffler[BG] rather took it for granted at first that his _Bacillus
typhi murium_ was harmless for man. In order to remove the fears of
the peasants in his campaign against the field mice in Thessaly he fed
pieces of bread impregnated with the cultures to chickens, pigeons,
dogs, hogs, horses, asses, sheep, and goats. No ill effects resulted.
Further, some of the men who were distributing the prepared virus ate
pieces of the infected bread in the presence of all and, it appears,
suffered no ill effects.
Footnote BG:
Loeffler, F.: Die Feldmausplage in Thessalien und ihre erfolgreiche
Bekämpfung mittels des Bacillus typhi murium. Centblt. f. Bakt.,
vol. 12, 1892, p. 1.
Up to this time Loeffler had made no human experiments, but thought it
improbable that his bacillus was harmful to man. He considered this
view confirmed by the fact that he and his companions and still more
so the peasants, handled large quantities of the virus without
thorough disinfection of their hands and suffered no untoward effects.
Since that time, however, several mishaps have occurred. Instances of
serious sickness and even death have been attributed to infection with
the bacterial virus used for the destruction of rats.
Further, there is practically no difference between the _Bacillus
typhi murium_ and the para-typhoid bacillus which is the well-known
cause of meat poisoning, and the _Bacillus enteridion_ of Jarbues,
which is associated with intestinal disorders.
It is true that persons have purposely partaken of the rat virus to
prove that it is harmless to man; but it must be remembered that
persons have partaken of cultures of cholera, typhoid, and other
bacteria without apparent injury to themselves. The flora and
condition of the gastro-intestinal tract, the amount and virulence of
the infection, and other conditions (“Y” and “Z” of Pettenkofer) play
an important rôle in the production of these diseases.
The following references from the literature give the instances in
which the _B. typhi murium_, or similar rat viruses, have been held
responsible for the disease in man:
Trommsdorff[BH] carefully studied 13 suspected cases near Munich in
early May, 1903. Nine of these came into direct contact with the
virus, three ate and associated with these, and the remaining one only
smelled of the virus. One died from vomiting and severe diarrhea. The
illness, which set in usually two days after contact with the virus,
was for the most part simple diarrhea of two to seven days’ duration
(two to eight stools daily); in only three or four cases was there
vomiting. The one fatal case seemed due to a confusing chain of
circumstances, gross dietetic and alcoholic excesses in a weak,
emaciated, presumably phthisical man whose three brothers had died of
phthisis. One man, case No. 2 in the table, known to have eaten three
pieces of infected bread, suffered only with a mild diarrhea.
Footnote BH:
Trommsdorff, R.: Ueber Pathogenität des Löfflerschen
Mäustyphusbazillus beim Menschen. Münch. med. Woch., vol. 50, 1903,
p. 2092.
In all cases errors of diet could be proven, and diarrhea was not
uncommon at that season. The same physician attended during this
period ten other cases of similar diarrhea in the vicinity having
nothing to do with rat virus. The stools, however, did not have the
same pathogenicity for mice, guinea pigs, or rabbits.
Trommsdorff specially points out the fact that the bacillus of mouse
typhoid can multiply vigorously in the human intestine. It demands
greater caution in the application of the cultures and more careful
supervision over their use.
Finally, attention is invited to the fact that, contrary to the usual
custom, the cultures of rat virus here used had been grown on milk,
which might account for the increased virulence.
The following table gives a brief summary of ten cases with the
results of the agglutination tests:
_Agglutination tests with serum of recovered cases, May 17, 1908._
──────┬─────────────────────────┬────────┬─────────────────────────────
Case. │ How infected; symptoms. │Strains.│ Serum dilutions.
„ │„ │„ │¹⁄₂₀ │¹⁄₄₀ │¹⁄₆₀ │¹⁄₁₀₀│¹⁄₂₀₀
──────┼─────────────────────────┼────────┼─────┼─────┼─────┼─────┼─────
1 B. │(From this case stool 2.)│A │ + │ + │ + │ ± │ 0
K. │ Laid rat poison │ │ │ │ │ │
│ 5–2,5–5; some days │ │ │ │ │ │
│ later diarrhea; later │ │ │ │ │ │
│ vomiting; convalescence│ │ │ │ │ │
│ and recovery May 10. │ │ │ │ │ │
„ │„ │B │ + │ + │ + │ ± │ 0
„ │„ │C │ + │ + │ + │ ± │ 0
„ │„ │D │ + │ + │ + │ + │ ±
──────┼─────────────────────────┼────────┼─────┼─────┼─────┼─────┼─────
2 K. │Ate three pieces of │A │ + │ 0 │ 0 │ 0 │ 0
E. │ infected bread May 2; │ │ │ │ │ │
│ mild diarrhea several │ │ │ │ │ │
│ days. │ │ │ │ │ │
„ │„ │B │ + │ ± │ 0 │ 0 │ 0
„ │„ │C │ 0 │ 0 │ 0 │ 0 │ 0
„ │„ │D │ + │ ± │ 0 │ 0 │ 0
──────┼─────────────────────────┼────────┼─────┼─────┼─────┼─────┼─────
3 H. │Brought the virus April │A │ + │ 0 │ │ │
B. │ 28; perhaps touched it;│ │ │ │ │ │
│ next day diarrhea and │ │ │ │ │ │
│ vomiting; recovery │ │ │ │ │ │
│ after several days. │ │ │ │ │ │
„ │„ │B │ + │ 0 │ │ │
„ │„ │C │ + │ 0 │ │ │
„ │„ │D │ − │ − │ − │ − │ −
──────┼─────────────────────────┼────────┼─────┼─────┼─────┼─────┼─────
4 G. │Father of man that died; │A │ + │ + │ + │ + │ 0
S. │ laid virus; two days │ │ │ │ │ │
│ later mild diarrhea for│ │ │ │ │ │
│ one or two days. │ │ │ │ │ │
„ │„ │B │ + │ + │ + │ + │ 0
„ │„ │C │ + │ + │ + │ 0 │ 0
„ │„ │D │ + │ + │ + │ + │ ±
──────┼─────────────────────────┼────────┼─────┼─────┼─────┼─────┼─────
5 J. │On April 27 laid virus; 2│A │ ± │ 0 │ 0 │ 0 │ 0
K. │ days later diarrhea for│ │ │ │ │ │
│ several days. │ │ │ │ │ │
„ │„ │B │ ± │ 0 │ 0 │ 0 │ 0
„ │„ │C │ ± │ 0 │ 0 │ 0 │ 0
„ │„ │D │ − │ 0 │ 0 │ 0 │ 0
──────┼─────────────────────────┼────────┼─────┼─────┼─────┼─────┼─────
6 J. │Laid virus April 27; two │A │ 0 │ 0 │ 0 │ 0 │
N. │ days later had diarrhea│ │ │ │ │ │
│ for several days. │ │ │ │ │ │
„ │„ │B │ + │ + │ + │ ± │
„ │„ │C │ 0 │ 0 │ 0 │ 0 │
„ │„ │D │ + │ + │ + │ ± │
──────┼─────────────────────────┼────────┼─────┼─────┼─────┼─────┼─────
7 G. │“Held” the virus April │A │ + │ + │ + │ + │ ±
I. │ 28. Next day diarrhea │ │ │ │ │ │
│ for four days. │ │ │ │ │ │
„ │„ │B │ + │ + │ + │ + │ ±
„ │„ │C │ + │ + │ + │ + │ ±
„ │„ │D │ − │ − │ − │ − │ −
──────┼─────────────────────────┼────────┼─────┼─────┼─────┼─────┼─────
8 H. │Ate and associated with │A │ + │ + │ 0 │ │
R. │ persons who handled │ │ │ │ │ │
│ virus; diarrhea several│ │ │ │ │ │
│ days. │ │ │ │ │ │
„ │„ │B │ + │ − │ 0 │ │
„ │„ │C │ + │ ± │ 0 │ │
„ │„ │D │ − │ − │ − │ │
──────┼─────────────────────────┼────────┼─────┼─────┼─────┼─────┼─────
9 K. │Associations as case 8; │A │ + │ + │ + │ + │
S. │ headache several days │ │ │ │ │ │
│ and loss of appetite. │ │ │ │ │ │
„ │„ │B │ + │ + │ + │ + │
„ │„ │C │ + │ ± │ 0 │ │
„ │„ │D │ − │ − │ − │ − │ −
──────┼─────────────────────────┼────────┼─────┼─────┼─────┼─────┼─────
10 │Associations as case 8; │A │ 0 │ 0 │ 0 │ 0 │
│ diarrhea for eight │ │ │ │ │ │
│ days; vomiting several │ │ │ │ │ │
│ days. │ │ │ │ │ │
„ │„ │B │ + │ + │ + │ ± │
„ │„ │C │ 0 │ 0 │ 0 │ 0 │
„ │„ │D │ + │ + │ + │ ± │
──────┴─────────────────────────┴────────┴─────┴─────┴─────┴─────┴─────
A = Strain from Loeffler.
B = Strain from market virus.
C = Strain from stool 1 (fatal case).
D = Strain from stool 2 (case 1 of table).
− = No test made.
0 = Negative.
± = Slight.
Controls = Serum of five normal persons tested as above; gave in no
case agglutination higher than 1 : 20.
The attending physician, noting that most of his patients had come
into recent contact with rat virus (_B. typhi murium_) and suspecting
that to be responsible, sent specimens of stools to the Hygienic
Institute at Munich, where they were carefully examined with reference
to this subject.
Organisms identical with Loeffler’s _B. typhi murium_ were isolated
from the two stools examined and these cultures were compared with and
conformed with a culture of _B. typhi murium_ obtained from Loeffler
and also a culture from the virus on the local market.
Two guinea pigs injected with cultures from the two stools gave, after
the second injection, serum which agglutinated all the above organisms
1:200. A mouse typhoid serum obtained from Loeffler agglutinated all
the above strains distinctly in dilutions 1:640 and slightly in
1:1280.
In conclusion, the author considers three possibilities: 1. The mouse
typhoid bacillus was the cause of the illness. 2. The bacillus was
accidentally present, having no part in the production of the
symptoms. 3. The bacillus was able to multiply only in case
pre-existing intestinal trouble; then, however, causing the
inflammation.
The case of Mayer, who became infected during the course of some
laboratory experiments, is particularly instructive.
During an epidemic of mouse typhoid among his laboratory mice,
evidently spread from some inoculated mice by ants, Mayer[BI] who had
personally handled the infected mice and their cages, became sick July
15, just seven days after the first appearance of the ants and after
the observed rise in virulence of the mouse typhoid among the mice.
His clinical history is as follows:
Footnote BI:
Mayer, Georg: Ueber die Verschleppung typhöser Krankheiten durch
Ameisen und die Pathogenität des Loeffler’schen Mäusetyphusbazillus
für den Menschen. Münch. med. Woch., vol. 52, 1905, p. 2261.
July 15: Weakness, epigastric pain, obstipation, temperature 37.7,
pulse 90.
July 16: Slight diarrhea, increase of pain in region of trans-colon,
temperature 38.3, pulse 98.
July 17: Diarrhea continued, pains increased—severe, chill in evening,
temperature 39.1, pulse 102.
July 18: Obstipation, symptoms worse, chill again in evening,
temperature 39.4, pulse 104.
July 19: Symptoms better, stools from purgative, evening temperature
36.9, pulse 68.
July 20: Left bed. Temperature and pulse normal, but weakness and
slight epigastric pains continued till August 7.
Patient’s serum agglutinated as follows:
──────────────────────────┬──────────────┬──────────────┬──────────────
│ Typhoid. │ Paratyphoid. │Mouse-typhoid.
──────────────────────────┼──────────────┼──────────────┼──────────────
July 23 │ 1–50+│ 1–50+│ 1–250+
August 7 │ 1–50+│ 1–50+│ [BJ]1–100+
August 16 │ 1–50+│ 1–50+│ 1–50 +
──────────────────────────┴──────────────┴──────────────┴──────────────
Footnote BJ:
Slight
The bacillus of mouse typhoid was isolated from the patient’s stools
July 21 and 23. Negative results thereafter. Examinations continued a
month.
Same organism isolated from urine July 21. Negative thereafter.
The author concludes that the _B. typhi murium_ is able to cause in
man a rather severe acute illness of short duration.
Shibayama[BK] gives the following report of outbreaks of human
infection that have come to his knowledge in Japan, where
mouse-typhoid virus has been used in considerable quantities.
Footnote BK:
Shibayama, G.: Ueber Pathogenität der Mäusetyphusbazillen für den
Menschen. Münch. med. Woch., May, 1907, p. 979.
_Outbreak 1._ In April, 1905, in a village of the Province of Saitama,
30 people became ill and 2 died with severe gastro-intestinal
symptoms. Outbreak investigated by Dr. H. Sezuki, district medical
officer, formerly of the Tokio Institute for Infectious Diseases.
It was found that all the 30 people had partaken of a dish of cooked
vegetables served at a meeting of the town council, and that for
application of sauce to these vegetables (after cooking) a wooden
vessel had been used which two days before had been used for mixing
mouse-typhoid virus with meal, without subsequent cleansing or
sterilization.
The symptoms came on within twelve to forty-eight hours thereafter
(usually twenty hours), chill or chilly sensations, rise of
temperature to 38° or 39° C., or even to 40° C.; face flushed; pulse
accelerated; great weakness; thirst, nausea, colicky pains in abdomen
followed by severe diarrhea and vomiting. In general, the fever and
diarrhea lasted two or three days; but malaise, anorexia, weakness,
and mucous stools persisted for several days. The more severe cases
showed choleraic symptoms of collapse. Two persons died in spite of
medical treatment—a 6-year old boy and a man of 43, on the second and
third day, respectively.
From the intestinal contents of these two cases, from the stools of
several other cases, and from the remnants of the dish of vegetables
in the wooden bowl an organism was isolated, which was demonstrated to
be identical with the bacillus of mouse typhoid.
These results were confirmed at the Tokio Institute for Infectious
Diseases by Shibayama, by biological and immunizing tests.
_Outbreak 2._ On December 7, 1905, a peasant of a village in the
Province of Miyaki brought home some mouse virus mixed with meal in
cakes. This being mistaken for “mochi” was eaten about 2 p. m. the
next day by two little girls, 3 and 8 years old, respectively, and
their grandfather, 61 years old.
The man and the 8-year-old girl became sick at 9 p. m. the same day
and the other child at about 3 p. m. on December 9. The symptoms in
all cases were those of severe gastro-enteritis, as described under
outbreak 1.
The man died December 12, the 8-year-old child died on the 10th; the
3-year-old child recovered after several days’ illness. These three
alone ate of the virus and no other persons in the house became sick.
No bacteriological examination was practicable.
_Outbreak 3._—In a village of the Province of Iskawa, on April 22,
1906, a lot of rat poison was prepared by mixing agar cultures of the
mouse-typhoid bacillus with meal and water in a large wooden bowl.
On April 24 there was a festival in the village at which about 170
persons were served with 240 pounds of rice, which, after being
cooked, was kneaded into cakes in a wooden bowl. About 80 pounds of
this rice was so kneaded in the bowl previously used for preparing the
rat poison. Twenty to twenty-four hours later 120 people who had eaten
of the rice became ill with the already described symptoms of
gastro-enteritis, of mild type among the strong but severe among the
children and old people. Eighty-nine cases came under medical
treatment. There were no deaths, but a number of cases were confined
to bed for a week or more; mild cases recovered in one to three days.
No bacteriological examination was made, but the physicians and town
officials were unanimously of the opinion that the rat virus was the
cause of the outbreak.
_Outbreak 4._—A peasant of the province of Niigata brought home on May
14, 1906, some rat virus (cultures of mouse-typhoid bacilli mixed with
meal) which he laid away. Two of his grandchildren—a boy of 5 and a
girl of 7—together with the 4-year-old daughter of a neighbor, found
and ate the rat virus. The next day all three children became ill with
severe gastro-enteritis, of which the 4-year-old child died on the
third day. The others recovered after several days of medical
treatment.
_Outbreak 5._—On May 16, 1906, a peasant in the province of Jamagata
brought home some rat virus (6 c. c. cultures of mouse-typhoid
bacillus mixed with meal), which was accidentally mixed with the feed
given to a healthy horse next morning. The same evening the horse
showed loss of appetite and appearance of sickness. Within two days he
developed a severe enteritis, of which he died on the seventh day. The
body was buried, but was dug up in the night by a laborer who cut off
the hind quarters, took them home, and distributed the meat among
friends and neighbors.
Within three days 34 persons who had eaten of this meat became ill
with symptoms of severe gastro-enteritis. A 72-year-old man died after
five days; the others recovered in three to eleven days.
This outbreak was investigated by Dr. H. Segawa, a medical officer of
the province and former member of the institute at Tokyo, who isolated
from the remains of the horseflesh by plate cultures and animal
inoculations, an organism identical with the bacillus of mouse
typhoid. A culture was sent to Shibayama, who carefully verified it
(details not given).
Shibayama concludes: In all cases the close relationship between the
bacillus of mouse typhoid and the illness was established; and he
thinks this organism must be accepted as the direct cause of the
outbreaks.
Referring to Loeffler’s uniformly negative human experiments, he calls
attention to known cases where men have taken virulent cultures of
typhoid, diphtheria, etc., without infection. According to many
bacteriological investigations, _B. typhi murium_ is identical with
the bacillus of enteritis. If it is proven that the latter is a cause
of acute gastro-enteritis then the conclusion is likewise justified
that the _B. typhi murium_ is frequently pathogenic for man, causing
an acute gastro-enteritis.
Fleischanderl[BL] a reports six cases of illness—three severe and
three mild—occurring in his practice in the latter part of April,
1908, presenting the following symptoms: Onset with rapidly increasing
body pains, followed in a few hours by diarrhea, rise of temperature,
and general prostration; in the next two or three days aggravation of
the symptoms, fever (39° to 40° C.), copious diarrhea, vomiting (in
one case), severe body pains, vertigo, and considerable prostration.
Symptoms abated quickly in a few days, leaving considerable
prostration, convalescence requiring two weeks in one case. In the
less severe cases there was no fever, and the other symptoms were
generally milder.
Footnote BL:
Fleischanderl, Fritz: Mitteilung über einige Krankheitsfälle,
hervorgerufen durch Mäustyphusbazillen. Munch. med. Woch., vol. 56,
Feb., 1909, p. 392.
The simultaneous appearance of these and other similar rumored mild
cases among the neighbors (about 20 in all) pointed to a common cause.
It was found that three of the six cases were in people who had
handled mouse-typhoid cultures the day before their illness, taking no
precautions to avoid infection.
The other three occurred in a family which, on the day before the
onset of the illness, had drunk raw milk obtained from a house where
the rat virus had been used shortly before, and only three members of
the family who drank the milk became ill.
In order to prove the etiology of these cases Fleischanderl, who had
never suffered any intestinal troubles, had had nothing to do with any
case of typhoid fever for a year, and was in excellent health, took a
culture of the mouse-typhoid bacillus as used in the neighborhood,
rubbed a glass rod over the surface, washed it off in a glass of
water, and drank this before breakfast on the morning of May 3.
In twenty-two hours he experienced mild, increasing body pains,
followed within a few hours by diarrhea, and a few hours later by
slight chill, rise of temperature to 38.2, pulse 106, severe pains in
body, and feeling of great weakness.
May 4, 9 p. m.: Temperature 39.2° C., pulse 120. Height of symptoms.
May 5: Temperature 38.2° to 38.5° C., pulse 106 to 120. Other symptoms
continued.
May 6: Temperature and pulse normal. All symptoms disappeared except
weakness, which lasted two days.