The Indian medical gazette. 1927 Nov; 62(11): 614-6

Roland Heynkes 25.9.2025, CC BY-SA-4.0 DE

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nach oben NR BAAC

nach oben AU Félix d'Herelle, R.H. Malone

nach oben TI A Preliminary Report of Work Carried out by the Cholera Bacteriophage Enquiry

nach oben QU The Indian medical gazette. 1927 Nov; 62(11): 614-6

nach oben AB kein Abstract

nach oben VT From April 27th to June 20th, 1927, we studied in detail 23 cases of cholera undergoing treatment at the Campbell Hospital, Calcutta. A large number of other cases of cholera were also studied (about 50), and as far as the incomplete experiments showed, the results were identical with those described below.
The observations made concerning the behaviour of the bacteriophage during the course of the disease may be summarized as follows:
During the period mentioned the bacteriophage seems to have been extremely widespread in Calcutta, for we were able to isolate bacteriophages virulent for vibrios from the intestinal contents of the patients immediately after their admission to hospital, i.e., from 10 to 20 hours after the onset of the disease.
(1) However, in three of the cases studied, the bacteriophage was not present in the intestine on admission to hospital, and these cases all died a few hours after admission. In this connection it may be mentioned that in 1921, while in Indo-China, the senior author was unable to isolate bacteriophages in 100 cases of cholera, all of whom died.
(2) In 2 cases a strong bacteriophage was present in the first stool passed after admission. These two patients recovered in an extremely rapid manner and were discharged from hospital 2 and 3 days respectively after admission, in spite of the apparent gravity of the symptoms at the time of admission.
(3) In three cases, all of whom died, the bacteriophage was weak from the onset, became still weaker, and finally disappeared.
(4) In the great majority of cases (13 out of 23) the virulence of the bacteriophage for the cholera vibrio, feeble at the onset, became exalted in a fairly rapid manner, and attained its maximum potency 24 to 48 hours after the onset of the disease. All these cases recovered, improvement commencing from the time when the bacteriophage was capable of producing complete bacteriophagy in vitro.
(5) In two cases there were fluctuations in the activity of the intestinal bacteriophage; weak at the beginning, it increased rapidly in potency, then diminished and again regained its power. With this reappearance of potency the patient's convalescence commenced.
Finally:
3 cases, no bacteriophage present on admission : 3 died within 24 hours.
3 cases, bacteriophage feeble and then disappeared: 3 died within 24 hours after disappearance.
2 cases, strong bacteriophage at the moment of the admission: 2 prompt recoveries.
13 cases, weak bacteriophage, the potency of which rapidly increased, 13 delayed recoveries.
2 cases, the power of the bacteriophage fluctuated, but finally became potent: 2 delayed recoveries.
Those experiments show that in cholera the end result, recovery or death, is intimately associated with the behaviour of the intestinal bacteriophage.
All the patients observed were treated by Roger's method of intravenous saline injections, which we may remark en passant is entirely rational: it prolongs the life of the patient until such time as the bacteriophage has become sufficiently exalted in virulence to overcome the pathogenic vibrios. This treatment is ineffectual when the bacteriophage is absent, as in the six fatal cases studied by us.
The Power to attack vibrios is not the same for all races of bacteriophage. Experiments have shown that certain races are capable of destroying in 3 or 4 hours all the vibrios of a culture. Others are much weaker and can only reduce the number of vibrios, without destroying them all.
Success in the treatment of diseases by means of bacteriophages depends entirely on the potency of the bacteriophage introduced into the organism of the patient. Then the first thing to be done before considering the question of treatment was to choose the most potent races of bacteriophages from amongst those isolated from the patients studied. Two such were provided by the two patients in whom bactenophage was potent from the beginning and who recovered very rapidly. But we have further attempted to obtain, and have in fact obtained, a further exaltation in potency by the passage of these races through other patients. We were then ready to conduct experiments in the treament of cholera by bacteriophage.
Experiments carried out in the Punjab, July 7th to August 9th.
First we have verified the facts observed in Calcutta. Here also, recovery or death depends entirely on the behaviour of the bacteriophage.
Further, we have studied the course of events in cholera epidemics in villages. Unfortunately (with but one exception) we have always received the information of the outbreak of epidemics some days after the onset. At this time the bacteriophage is extremely widespread in the environment, principally in well water and in flies, and it has been possible to isolate very potent races of bacteriophages from these sources.
We have also observed in a village which has not been infected with cholera during the year, that neither the well water, nor flies caught in the village contained any bacteriophage virulent for cholera vibrio.
From those facts it would appear that the bacteriophage virulent for cholera vibrio is not present in the environment before an epidemic, but only makes its appearance during the course of the epidemic.
This is our explanation of the course of a village epidemic, based on the facts observed in India, as well as on facts observed in the course of epidemics of bacillary dysentery in man and various epizootics in animals (fowl typhoid, hemorrhagic septicaemia in buffaloes, and plague in rats).
The cholera vibrios are imported into the village, or the town, with the first case; from the first case they are disseminated by direct contact, by means of flies or well water. All patients in whom the intestinal bacteriophage remains inert towards the cholera vibrio succumb, and they are in the majority. There are some others, however, in whom there is a rapid exaltation of the virulence of the normal intestinal bacteriophage towards the cholera vibrio, and these individuals enter into convalescence. Virulent bacteriophages from these convalescents are passed with the stools, and are spread in exactly the same manner and by the same agents as are the pathogenic vibrios. In a word, at the beginning there are disseminated into the environment the cholera vibrios, and this is the period of the propagation of the disease. Then from the first convalescent there are disseminated the bacteriophages. As more and more patients recover, the bacteriophages become more and more disseminated, and the epidemic declines, finally to cease when "contamination" by the bacteriophage becomes general.
Finally, we have carried out experiments in the treatment and prevention of cholera. As we have said before, generally the epidemics are not reported by the headmen of the villages until they are nearly over. For that reason we have not been able to treat as many cases as we should have wished, for in only four villages could we initiate treatment at a stage early enough to havea fair mortality amongst the non-treated cases; those were generally treated by the mixture of essential oils.
The results of those experiments are given below.

Names of villages Dates. Cases not treated by bacteriophage. Cases treated by bacteriophage.
before Cases. Deaths. Cases. Deaths.
Ghawinpi 13-7
14-7
15-7
16-7
9
2
3
2
8
2
1
2
..
11
1
..
..
0
1
..
16 13 12 1
Waigal .. 13-
14-7
15-7
16-7
17-7
18-7
20⋅23-7
15
9
15
0
1
2
?
8
0
13
0
5
0
(8)
..
..
1
7
4
1
0
..
..
0
0
0
0
1
42 26+(8) 13 1
Jaman .. 6-15-7
16-7
17-7
18-7
25-30-7
26
..
..
..
(42)
17
2
..
..
(19)
1
4
3
1
..
0
0
0
1
..
26 19 9 1
Rajiana .. 21-7
22-7
23-7
24-7
25-7
26-7
13
5
5
0
0
0
0
2
4
1
1
2
5
2
..
..
..
..
0
0
..
..
..
..
23 10 7 0
Names of the villages Dates Cases not treated by bacteriophages. Cases treated by bacteriophages
As we have said before, in only one instance the health authorities were advised by wire of an outbreak of an epidemic in a village. Nawar. We here availed ourselves of the opportunity of undertaking a trial of prophylaxis.
Nawar is a village of 345 houses, the majority of the population being Jats. It is provided with water by 13 public and 9 private wells. Six cases occurred on the 2nd of August with 3 deaths, and 6 cases on the 3rd with 2 deaths. On the 4th of August 30 c.c. of a culture of a selected bacteriophage were added to each of the two Jat wells supplying the contaminated area. Not a single case of cholera has been reported since; all the patients who were Jats and drank water from those wells recovered.
This single experiment evidently is lacking in any value by itself, but it must be remarked that the senior author conducted extensive experiments in fowl typhoid, since confirmed in Holland, with the result that in every case the epizootic stopped immediately after experimental spreading of the bacteriophage in the environment.
We must remark that by the use of cultures of selected virulent bacteriophages we have reproduced experimentally the natural process of the recovery, as well as the natural process by which epidemics come to an end. But in the natural way, the exaltation of the virulence of the bacteriophage (contained in the intestine of every man or animal, but normally not virulent for the cholera vibrio), for the pathogenic vibrio depends on favourable or unfavourable circumstances which may occur sooner or later in the course of the epidemic.
Experimentally, we can choose a race of the most virulent bacteriophage, already adapted to the rapid destruction of cholera vibrios. We can spread cultures of it over or at the very beginning of an epidemic more widely and more rapidly than is possible in the natural course of the events.

nach oben SP englisch

nach oben ZF 1927 untersuchten d'Herelle und Malone im indischen Campbell-Krankenhaus Calcutta im Detail den Verlauf von 23 Fällen von Cholera mit und ohne Phagen-Behandlung. Die Untersuchung von ungefähr 50 weiteren Fällen war zum Zeitpunkt der Publikation noch nicht abgeschlossen, aber die Verläufe entsprachen den 23. Bei 20 der 23 etwa 10-20 Stunden nach Beginn der Krankheit eingelieferten Patienten konnten aus den Darminhalten Phagen isoliert werden, die im Labor Cholera-Vibrionen lysierten. Die anderen 3 Paienten starben trotz konventioneller Behandlung wenige Stunden nach der Einlieferung. 1921 hatte einer der Autoren in Indo-China (1921 eine Föderation französischer Kolonien im Gebiet der heutigen Staaten Vietnam, Kambodscha und Laos) bei 100 Patienten vergeblich versucht, Bakteriophagen aus den Darminhalten zu isolieren. Alle Patienten starben.


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