Sunteți pe pagina 1din 4

Vol.

33

Studies on Epidemic Diarrhea of the


New-born: Isolation of a Filtrable
Agent Causing Diarrhea in Calves*
JACOB S. LIGHT, M.D., AND HORACE L. HODES,
LT. MC, USNR
Harriet Lane Home of the Johns Hopkins Hospital and Department of Pediatrics
of the Johns Hopkins University; and Sydenham Hospital, Baltimore
City Health Department, Baltimore, Md.

DURING the past two years we have producing organisms. In each of the
had the opportunity of studying four epidemics, stool of affected babies
six separate epidemics of diarrhea of was given nasally to a calf. This ma-
the new-born occurring in three hospi- terial was Seitz filtered in three of the
tals in the Baltimore-Washington area. instances, unfiltered in the fourth. In
This study has been approached from all four instances there followed in the
the standpoint of a possible filtrable calf a bloody, mucoid diarrhea with
agent etiology of the disease. comparable incubation period and clini-
The first two epidemics occurred al- cal characteristics.
most simultaneously at two Baltimore On the first occasion in which this
hospitals in the early fall of 1941. result was obtained in the calf, the
Stools, blood, and nasal washings were question arose as to whether attempt
obtained from a number of the babies at further serial calf-to-calf passage
and injected by various routes into a would be worth while. The calf, like
variety of the smaller animals. No the human infant, is naturally prone to
definite disease resulted in any of the diarrheal episodes from a variety of
animals. causes, and the mere occurrence of
The subsequent four epidemics oc- diarrhea following injection in a calf
curred during 1942, two of them in the would not necessarily signify that suc-
full-term nursery of a Baltimore hos- cessful passage had been carried out.
pital and two in the premature nursery However, in view of the presence of
of a Washington hospital. All four blood and mucus in the stools of this
were characterized by a high morbidity first calf, it was hoped that if there
rate; in the last three of these epidemics were an agent here which could be pas-
the mortality was high, while in the saged, the clinical picture in the calf
first, occurring among full-term babies might be distinctive enough to provide
during the month of March, the mor- fairly reasonable assurance of successful
tality was low. Stool cultures were passage. This hope has apparently
uniformly negative for known diarrhea- been realized; successive calf passages
were found readily possible with each
*
Presented at a Joint Session of the Epidemiology,
of the four strains and the results of
Health Officers, Maternal and Child Health, and cross-immunity studies have indicated
Laboratory Sections of the American Public Health that the four strains represent a single
Association at the Seventy-second Annual Meeting in
New York, N. Y., October 14, 1943. agent.
[1451]
1452 AMERICAN JOURNAL OF PUBLIC HEALTH Dec., 1943

Up to the present time this disease hibiting a certain amount of variability,


has been produced in a total of 84 was uniformly characterized by the
calves. In the case of the first strain occurrence of diarrhea with the produc-
there have so far been carried out 29 tion of mucus, usually in very large
successive passages, 10 of which were amounts. Almost every calf also showed
with filtered material; with the second blood in the stools at some time during
strain 4 successive passages, 2 of them the course of the disease. As a rule,
filtered; with the third strain 8 suc- constitutional reaction was minimal, and
cessive passages, 6 filtered; and with the aside from mild dehydration and ano-
fourth strain 2 passages, both filtered. rexia at the height of the process, the
The majority of the calves used have calves would usually not seem particu-
been of the Guernsey breed, and these larly ill. Temperatures were taken on
were found quite satisfactory. In Hol- a few of the calves and very little fever
stein calves the disease did not seem was found.
quite so typical and one Holstein calf The disease proved to be of a pecu-
was apparently not susceptible. Aside liarly relapsing nature in the calf, and
from this single animal, the calves used in rare animals the mucoid diarrhea
were found uniformly susceptible. Ages actually became chronic. In those
of the animals ranged from 2 days to 2 calves which survived, the total dura-
months. Most of them were in the 1 tion of the process varied from 8 to
to 3 week age period, and in calves 54 days; in the average case the dura-
older than this the clinical disease tion was in the neighborhood of 3 weeks.
tended to be milder. Most of the animals recovered, the mor-
Passage material consisted of saline tality being about 13 per cent. Immun-
suspension of infected calf stools ob- ity was found to be present following
tained during the acute stage of the recovery, large doses of active material
disease. The material was frozen when then causing no disease.
obtained and stored in a dry ice con- On gross pathological examination
tainer until ready for use, then thawed both small and large intestine showed
at 370 C. and given by simple nasal hyperemia, while the intestinal lym-
injection. The minimum dose uni- phoid tissue was swollen and the mes-
formly successful in passage was 1.0 ml. enteric lymph nodes appeared enlarged.
With Seitz filtrate preparations of this Microscopically, there were found areas
material a larger dose was necessary, of infiltration of the intestinal wall with
the smallest successful dose ever used polymorphonuclear leukocytes and in
being 8.0 ml. Material given nasally one very severe case ulcerations of the
to the unanesthetized calf is swallowed mucosa, while the intestinal lymphoid
and it may be that the portal of entry tissue and the mesenteric lymph nodes
for the agent is actually within the appeared hyper-plastic.
gastrointestinal tract, as the one at- Three attempts were made at pas-
tempt made at passage through the age with the use of the blood of in-
use of a stomach tube was successfully fected calves. The first attempt failed.
accomplished. The other two, made with blood taken
The clinical disease in these calf-to- from exceptionally sick calves during
calf passages was quite similar to that the latter part of the first week of the
which followed the injection of material disease, were successful, and it is inter-
from the babies in the four epidemics esting that one of the calves that came
mentioned above. The incubation down from this material had been inoc-
period regularly ranged from 2 to 5 ulated by the subcutaneous rather than
days. The disease itself, though ex- the nasal route.
Vol. 33 DIARRHEA OF THE NEW-BORN 1453

Susceptible calves exposed to infected duction of a very mild disease of short


calves were found to acquire the disease duration, with prolonged incubation
by cross-infection. In a few of the in- period. This very mild disease pro-
stances the disease thus acquired was duces immunity, as a subsequent inocu-
clinically very mild, with relativelv pro- lation with fully active material results
longed incubation period, but in most of in no observable disease. When the
the cases the picture produced was quite stools from this very mild disease are
typical. further passaged, 2 serial passages re-
In view of the fact that cross-infec- sult in the reestablishment of full
tions could occur, it was obviously virulence.
necessary to enforce strict isolation of Heat inactivation experiments, car-
animals used in this study. This was ried out by the submerged sealed tubes
accomplished by isolating calves singly method, are as yet incomplete. The
in a number of widely separated areas data so far available seem to indicate
such as farms where there were no other that the agent is not regularly inacti-
calves present. vated by boiling for 5 minutes, but is
In a consideration of the probable regularly inactivated by boiling for 10
nature of the agent discussed in this minutes. Heating at 70 C. for 1 hour
paper, one of the first questions that apparently fails to inactivate the agent,
comes up refers to the possibility that but heating at 800 C. for 1 hour results
it is present in normal infant or calf either .in complete inactivation or in
stools. In this connection, the stools attenuation.
of 4 normal calves were given nasally Protection tests were carried out with
in large dose respectively to 4 different the use of the sera of 6 babies recovered
calves. No disease resulted in these from the epidemic in connection with
animals. The stools of 8 normal new- which the first strain of the agent was
born infants were similarly tested, a obtained. The data on these tests
pool of stools from 2 separate babies would require discussion too lengthy
being given to each of 4 calves. Again for the present occasion, but, in brief,
no disease resulted. it appeared that two of the sera showed
As to the properties of the agent, it complete protection, two showed prob-
was found to be readily filtrable through able protection, and two showed partial
Seitz filters, and cultures of filtrates protection. In this connection, with
on various aerobic and anaerobic media reference to the antigenicity of the
have been uniformly negative. The agent, a rabbit was given repeated small
longest series of successive Seitz filtrate intravenous injections of Seitz filtrate
passages that was attempted was 4, and of infected calf stool. Following this
this was successfully completed, each his serum showed protective antibodies.
calf in the series receiving Seitz filtrate This experiment was controlled by the
of the stools of the calf that preceded use of serum from a non-injected litter
him in the series. In view of the fact mate.
that the agent was not found in the The question arises as to whether
stools of normal calves, this would seem this disease occurs naturally among
to indicate that it is self-perpetuating. calves. The opportunity came up to
Activity is maintained for at least 2 study two herds of dairy cattle more or
months when the material is frozen at less chronically infected with calf
-70 C. and stored in dry ice. Material scours. In one of these herds a calf
which has been dried from the frozen was found whose clinical picture was
-state seems to undergo attenuation, and quite similar to that of the calves in-
when used in passage results in the pro- fected with the agent described above.
1454 AMERICAN JOURNAL OF PUBLIC HEALTH Dec., 1943

The studies which were carried out, pneumonia in the calves affected by the
however, indicated that the cause of his agent discussed in this paper, and
disease was not this same agent, and second because of failure with it of
at the present time it is impossible to transmission to mice even after a num-
say whether or not this disease occurs ber of serial mouse passages.
naturally among calves. The conclusions which seem justified
In this connection, another question from the data presented are:
comes up which refers to the possibility
1. In connection with four separate epi-
that this agent might actually be identi- demics of diarrhea of the new-born a
cal with the pneumoenteritis virus, iso- filtrable agent has been isolated which regu-
lated by Baker 1 from a natural disease larly produces diarrhea in calves.
of calves characterized clinically by 2. In the attempts so far made, this agent
pneumonia and diarrhea.
has not been isolated from the stools of
Though normal infants or normal calves.
samples of this virus were not available 3. The evidence suggests, though it is not
for experimental comparison, it seems conclusive, that the agent may be a cause
unlikely on the basis of the evidence of epidemic diarrhea of the new-born.
at hand that the two agents are the REFERENCE
same, first because of the absence of 1. Baker, J. A. Cornell Vet., 30:202-204, 1942.

S-ar putea să vă placă și