VII Cholera
The study of cholera was the hardest of all the hard labours of bacteriology; it took years of work in all parts of the world, and the difficulty and disappointments over it are past all telling. Koch’s discovery of the comma-bacillus (1883) raised a thousand questions that were solved only by infinite patience, international unity for science, and incessant research; and the Hamburg epidemic (1892) marks the time when the comma-bacillus was at last recognised as the cause of cholera. A mere list of the men who did the work would fill page after page; it was bacteriology in excelsis, often dangerous,26 and always laborious.
There is the same heroic note in the story of the preventive treatment of cholera by Haffkine’s method; one of the men in whom Pasteur seems to live again. He began in 1889, under Pasteur’s guidance, to study the immunisation of animals against the cholera-bacillus. Other men, of course, were working on the same lines—Pfeiffer, Brieger, Metchnikoff, Fischer, Gamaleïa, Klein, Wassermann, and many more—and by 1892 the immunisation of animals was proved up to the hilt. Then came the advance from animals to men, from laboratories to Indian cities, villages, and cantonments; and here the honour is Haffkine’s, and his alone. Ferran’s inoculations (Spain, 1885) had failed. Haffkine, having tested his method on himself and his friends, went to India, with a commendatory letter from the British Government:—
“Researches on cholera, with special reference to inoculation, were undertaken and carried on in my laboratory, in the Pasteur Institute in Paris, between 1889 and 1893. The experiments resulted in the elaboration of the present method, which when tried on animals was found to render them resistant against every form of cholera-poisoning otherwise fatal to them.
“The physiological and pathological effect on man was then studied on some sixty persons, mostly medical and scientific men interested in the solution of the problem. The effect was found to be harmless to health. The next step was to transfer the operations to the East.” (Haffkine’s Report to the Government of India, 1895.)
He reached Calcutta in March 1893, and at the request of Mr. Hankin27 was invited to Agra; here, in April, he vaccinated over 900 persons, including many English officers. From Agra to Aligarh; and from Aligarh he was asked to more places than he could visit. In 1895 his health failed, and no wonder; and he came back to Europe for a short time:—
“My actual work in India lasted twenty-nine months, between the beginning of April 1893 and the end of July 1895. During this period the anti-cholera vaccination has been applied to 294 British officers, 3206 British soldiers, 6629 native soldiers, 869 civil Europeans, 125 Eurasians, and 31,056 natives of India. The inoculated people belonged to 98 localities in the North-West Provinces and Oudh, in the Punjab, in Lower Bengal and Behar, in the Brahmaputra Valley, and in Lower Assam. No official pressure has been brought on the population, and only those have been vaccinated who could be induced to do so by free persuasion. In every locality, efforts were made to apply the operation on parts of large bodies of people living together under identical conditions, in order to compare their resistance in outbreaks of cholera with that of non-inoculated people belonging to the same unit of population. This object has been obtained in 64 British and native regiments, in 9 gaols, in 45 tea-estates, in the fixed agricultural population of the villages parallel to Hardwâr pilgrim road, in the bustees of Calcutta, in a certain number of boarding-schools, where the parents agreed to the inoculation of their children, in orphanages, etc. The vast majority of inoculated people lived thus under direct observation of the sanitary and medical authorities of India.” (Haffkine, Lecture in London. British Medical Journal, 21st Dec. 1895.)
Altogether, upwards of 70,000 injections on 42,179 people—without having to record a single instance of mishap or accident of any description produced by our vaccines. Consider the colossal difficulties of this new treatment: the frequent running short of the vaccine, preventing a second injection; the absolute necessity, at first, of using very small doses of a weak vaccine, lest one disaster should occur; the impossibility of avoiding, now and again, some loss of strength in the vaccine; the impossibility of knowing how long the protection would last. Surely in all science there is nothing to beat this first voyage of adventure single-handed to fight the cholera in India.
Later than Haffkine’s 1895 report, we have Dr. Simpson’s 1896 report: “Two Years of Anti-choleraic Inoculations in Calcutta. W. J. Simpson, M.D., M.R.C.P., D.P.H., Health Officer, Calcutta.” The date of this report is 8th July 1896; and it gives not only the Calcutta results, but all that are of any use for exact judgment:28 —
“The results of Calcutta are fully confirmed by those obtained in other parts of India, wherever it was possible to make all the necessary observations with precision, and wherever the cases were sufficiently numerous to show the effect of the inoculation.
“Outside Calcutta, since the commencement of the inoculations in India in April 1893, opportunities for an exact comparison of the respective powers of resistance against cholera of inoculated and non-inoculated persons presented themselves; (1) in Lucknow, in the East Lancashire Regiment; (2) in Gaya, in the jail; (3) in Cachar, among the tea-garden coolies; (4) in Margherita, among coolies of the Assam-Burmah Railway Survey; (5) in Durbhanga, in the jail; (6) in the coolie camp at Bilaspur; (7) in Serampur, among the general population.”
Here, then, in this 1896 report, are all the results that give an answer to the question, What will happen when cholera breaks out among a number of people living under the same conditions, of whom some have received preventive treatment, and the rest have been left to Nature?
I. Calcutta (1894-1896)
“The number of people inoculated during the period under review was 7690; of these, 5853 are Hindus, 1476 Mahomedans, and 361 other classes.... Considering that the system is a new one, that the inoculations are purely voluntary, and everything connected with them has to be explained before the confidence of the people can be obtained, and considering how long new ideas are in taking root among the general population—and in this case it is not merely the acceptance of an idea, but such faith in it as to consent to submit to an operation—the number is certainly satisfactory for a beginning. The present problem can be compared with the introduction of vaccination against smallpox into Calcutta. It took 25 years before the number of vaccinations reached an average of 2000; whereas the inoculations against cholera have in two years nearly doubled that average. This is a proof that, in spite of the difficulties which every new movement naturally has to meet with, there are large numbers of people anxious to avail themselves of the protective effect of the inoculations.
“Although all sorts and conditions of individuals, weak and strong, sickly and healthy, young and old, well nourished and badly nourished, and often persons suffering from chronic diseases, have been inoculated, in every instance, without exception, the inoculations have proved perfectly harmless.
“The investigations on the effect of the inoculation are made exclusively in those houses in which cholera has actually occurred, the object being to ascertain and compare the incidence of cholera on the inoculated and not inoculated in those houses in which inoculations had been previously carried out. For this purpose, affected houses in which inoculations have not been performed, and inoculated houses in which cholera has not appeared, are excluded.”
Nature gave a demonstration in 77 houses. In one house, and one only, all the household had been inoculated; in 76, inoculated and non-inoculated were living together; but of these 76 houses, 6 are excluded from the table of results, because the inoculated in them were so few—less than one-tenth of the household—that their escape from cholera might be called chance. The cholera came, and left behind it this fact:—
654 uninoculated individuals had 71 deaths = 10.86 per cent.
402 inoculated in the same households had 12 deaths = 2.99 per cent.
If we add the 6 houses which Dr. Simpson excludes, we find that in 77 houses there were 89 deaths from cholera, 77 being among the uninoculated and 12 among the inoculated.
Moreover, of these 12 deaths, 5 occurred during the first five days after inoculation—that is to say, during the period in which the protective influence of the vaccine was still incomplete. Then came a period of more than a year, during which the uninoculated had 42 deaths, and the inoculated had one death. The remaining 6 of the 12 deaths occurred more than a year after inoculation, and 5 of these 6 had received only one inoculation of the weak vaccine that was used early in 1894.
Take a good instance that came at the very beginning of the work:—
“A local epidemic took place around two tanks in Kattal Began bustee, ward 19, occupied by about 200 people. In this bustee, about the end of March, 2 fatal cases of cholera and 2 cases of choleraic diarrhœa occurred. The outbreak led to the inoculation of 116 persons in the bustee out of the 200. Since then, 9 cases of cholera, of which 7 were fatal, and 1 case of choleraic diarrhœa have appeared in the bustee, and it is a very extraordinary fact that all these 10 cases of cholera have occurred exclusively among the uninoculated portion of the inhabitants, which, as stated, forms the minority in the bustee; while none of the inoculated have been affected.” (Cholera in Calcutta in 1894. W. J. Simpson.)
2. Lucknow (1893)
The story of the outbreak of cholera in the East Lancashire Regiment must be read carefully:—
“Rumour magnified the events connected with this outbreak, and distorted the facts connected with the inoculations; and as a result, the current of public opinion, which had previously been in favour of inoculation, set in strongly in the opposite direction. The advocates of anti-choleraic inoculations were abused in no particularly measured terms, and the inoculations were held up to be the source of every possible evil and danger... of the most loathsome diseases, and of every ill which man is heir to. The distrust engendered by these misrepresentations and fulminations was, however, only of a temporary nature; and when the exact circumstances came to be known and understood, the confidence created by the Calcutta experience began to be considerably restored. Inoculations were performed in May 1893, in the East Lancashire, Royal Irish, 16th Lancers, 7th Bengal Infantry, 7th Bengal Cavalry, and general populations in the Civil Lines. In 1894, cholera appeared among the native population of Lucknow, in the form of an epidemic distinguished by its extreme virulence, patients succumbing in the course of a few hours. It is stated that the epidemic was of a most malignant type. In the latter part of July it entered the cantonments, and attacked the East Lancashire, almost exclusively confining its ravages to that regiment.”
In the East Lancashire, 185 men were inoculated in May 1893. From the statistical returns obtained from the military authorities at Lucknow, it appears that at the time of the outbreak, in July 1894, the strength of the men, including those in hospital, was 773; and of these, 133 had been inoculated, as recorded in the inoculation register, and 640 had not been inoculated.
The following table shows the total number of attacks and deaths in not inoculated and inoculated:—
| Attacks. | Deaths. | |
|---|---|---|
| Per cent. | Per cent. | |
| Non-inoculated, 640 | 120 = 18.75 | 79 = 12.34 |
| Inoculated, 133 | 18 = 13.53 | 13 = 9.7 |
The men were moved into camp; but this movement seemed only to make things worse: “the epidemic in the camp appears to have been twice as severe as in the cantonment.”29
Lucknow came so early in the work of inoculation, that weak vaccines were used in small doses. The cholera, when it broke out, was “of a most malignant type, senior medical officers of long experience in the country stating that such a virulent cholera had not been seen by them for very many years past.” More than a year had elapsed between the inoculations and the outbreak of the cholera. It is no wonder that the regiment was not well protected:—
“The small amount of protection which the inoculations afforded in this case may have depended on the mild effects which the injections produced on the men at the time of the operation in 1893, in comparison with the severity of the epidemic which attacked the regiment. It is recorded in the Lucknow Inoculation Registers that only in two men, out of the 185 inoculated in 1893, a marked febrile reaction was obtained; in 77 individuals the vaccinal fever was only slight, while in 66 there was no reaction: an effect which was due to the weakness of the vaccines procurable at that period of work, and to the small doses used. The influence of the vaccines was possibly further reduced, at the time of the epidemic, by a lapse of fourteen to fifteen months.” (Haffkine, 1895 Report.)
3. Gaya Jail
On 9th July 1894, an outbreak of cholera occurred in the Gaya jail, and by 18th June there had been 6 cases and 5 deaths. On that day and the next day, 215 prisoners were inoculated. The average number of the prisoners during the outbreak was 207 inoculated, and 202 not inoculated. Surgeon-Major Macrae, superintendent of the jail, reports:—
“The inoculations being purely voluntary, no selection of prisoners was possible, but all classes of the jail were represented—male and female, old and young, habituals and less frequent offenders, strong and weakly, convalescent and even hospital patients sent their representatives; no difference of any kind was made between inoculated and non-inoculated; they were under absolutely identical conditions as regards food, water, accommodation, etc., in fact in every possible respect.”
Of course, the best results could hardly be obtained, because the cholera was already at work: it took about ten days for the 1894 vaccine to produce its full effect; and two inoculations were generally made, one five days after the other. This gradual action of the vaccine is well shown in Dr. Simpson’s table:—
| Non-Inoculated, 202 | Inoculated, 207 | |||
|---|---|---|---|---|
| Cases. | Deaths. | Cases. | Deaths. | |
| During 5 days after 1st | 7 | 5 | 5 | 4 |
| inoculation | ||||
| During 3 days after 2nd | 5 | 3 | 3 | 1 |
| inoculation | ||||
| After 3 days after 2nd | 8 | 2 | 0 | 0 |
| inoculation | ||||
Haffkine’s comment on these figures must be noted here:—
“In the Gaya jail, the inoculations were for the first time applied in a prevalent epidemic, and very weak doses of a relatively weak vaccine were used.... Far higher results have been obtained by an application of stronger doses. In the bustees situated round the tanks in Calcutta, where cholera exists in a permanent state, the disease occurred in 36 houses with inoculated people. In each of these houses there was one part of the family inoculated and another not. The observations were continued for 459 days, with the following results:—
During the first period of 5 days, subsequent to the inoculation with first vaccine, cholera occurred in 8 houses.
75 non-inoculated had 5 cases, with 3 deaths. 52 inoculated had 3 cases, with 3 deaths.
During the second period of 5 days, subsequent to the second inoculation, cholera occurred in 2 houses.
8 non-inoculated had 2 cases, with 2 deaths. 17 inoculated had no cases.
After the 10 days necessary for the preventive treatment had expired, and up to the 459th day, the disease visited 26 houses.
263 non-inoculated had 38 cases, with 34 deaths.
137 inoculated had 1 case, with 1 death, in a child that had not been brought up for the second inoculation.”
4. Assam-Burmah Railway
For a good instance of lives saved even during an outbreak, take the Assam-Burmah Railway coolies:—
“Three hundred and fifty 30 Khassia Hill coolies had been collected for the survey party of the Assam-Burmah Railway, and put under the escort of a detachment of Goorkhas, when cholera broke out amongst them. The largest part of the coolies immediately submitted to the preventive inoculation, the rest remained uninoculated. The result was that among the not-inoculated minority there were 34 cases, with 30 deaths; whereas the inoculated had 4 fatal cases.” (Haffkine, 1895, Lecture in London.)
5. Durbhanga Jail (1896)
The figures in this instance are small: but Surgeon-Captain E. Harold Brown’s report is very pleasant reading. Cholera broke out in the jail on 31st March 1896, and by 9th April there had been 8 cases. Next day, 172 prisoners were moved into camp 12 miles away; and 53 were left behind, the sick in the jail hospital, the patients in the cholera huts, with their attendants, the old and infirm, and a few cooks and sweepers. That day, 3 cases occurred in the camp, and 1 in the jail; and on the 11th, at 2 and 4 a.m., 2 more cases were reported in camp. At 7.30 a.m., Haffkine and Dr. Green came to the camp:—
“The prisoners were spoken to on the subject, and seemed to be pleased with the idea, the word tika (inoculation), which was familiar to them from its association with smallpox, appearing to appeal to them. They were accordingly arranged in four rows facing the tent, in front of which Dr. Haffkine was about to commence operations. I was the first subject to be inoculated; and after me the jailor, assistant jailor, hospital assistant, and three warders. The first prisoner in the front rank was next brought up and submitted cheerfully; after which, every alternate man was taken, so that no selection of cases was made, until one-half of the total number were inoculated. Those who had not been inoculated were far from pleased at having been passed over; and, to our surprise, they rose almost to a man, and begged to be inoculated; nor were they satisfied when told that the medicine was exhausted.”
The dose administered on this occasion (11th April 1896) was stronger than the Gaya jail dose (18th July 1894): it acted in a few hours, and the reaction was well marked.
“There were fresh cases of cholera that day at 12 (noon), 6, 7, and 7.30 p.m., and at midnight, all in those who had not been inoculated, and all terminating fatally, despite the greatest care and the most prompt and assiduous treatment. On the 12th two further cases occurred, both among the uninoculated, and both died; there being thus eight cases in succession, all from the men who were not inoculated, and all proving fatal.”
The inoculations were made at 7.30 A.M. Surgeon-Captain Brown had pain within half-an-hour, and fever in three hours, with temperature 104°, but this was probably due to the fact that I was not able to rest. The prisoners, of course, went to bed: they all reacted before 4 P.M., but did not have so much trouble over it. The last case was on the 15th. The outbreak was a bad type of cholera; out of 30 cases 24 died, some of them in 1-1/2 to 4 hours. “To summarise the combined results of the camp and the jail, we find that of a daily average of 99 non-inoculated there were 11 cases, all fatal = 11.11 per cent.; of 110 inoculated there were 5 cases, with 3 deaths = 2.73 per cent.”
6. Bilaspur and Serampur
Here again the figures are small, but worth noting. In a coolie camp at Bilaspur (Central Provinces) 100 non-inoculated had 5 deaths, and 150 inoculated had 1 death. In Serampur, among the general population, 51 non-inoculated had 5 cases and 3 deaths, and 42 inoculated had 2 cases and 1 death.
7. The Cachar Tea-Gardens (1895)
This series of inoculations was begun in February 1895, for the protection of the coolies on various tea-estates. The results are excellent, and deal with large numbers.31 The latest report from Dr. Arthur Powell, the Medical Officer, is quoted in Dr. Simpson’s 1896 report:—
At Kalain—
1079 not inoculated had 50 cases, with 30 deaths.
1250 inoculated—3 cases, with 2 deaths.32
At Kalaincherra—
685 not inoculated had 10 cases, with 7 deaths.
155 inoculated—no cases.
At Degubber—
254 not inoculated had 12 cases, with 10 deaths.
407 inoculated—5 cases, all recovered.
At Duna—
121 not inoculated had 4 cases, with 2 deaths.
29 inoculated—no cases.
At Sandura—
454 not inoculated had 2 cases, with 1 death.
51 inoculated—2 cases, with 1 death.
At Karkuri—
198 not inoculated had 15 cases, with 9 deaths.
443 inoculated—3 cases, with 1 death.
At Craig Park—
185 not inoculated had 1 fatal case.
46 inoculated—no cases.
Total.
Not inoculated, 2976, with 94 cases and 60 deaths. Inoculated, 2381, with 13 cases and 4 deaths.
To the preceding instances, which are rather old now, must be added the following more recent report, from the Indian Medical Gazette, September 1901:—
“We are glad to see, from a paragraph in the Report of the Sanitary Commissioner for Bengal (Major H. J. Dyson, I.M.S., F.R.C.S.), that an increased number of anti-cholera inoculations were performed during the year 1900. Assistant-Surgeon G. C. Mukerjee, who was in charge of this work, reports that in the Puralia Coolie Depot no less than 13,291 persons were inoculated against cholera, including over 1000 children. All these cases of inoculation were among labour emigrants proceeding to the tea-gardens of Assam and Cachar. The employers of labour are beginning to realise the value of cholera inoculation. It is unfortunately not always easy, or even possible, to follow up the after-history of persons inoculated; but Major Dyson has quoted a table, received from the Superintendent of Emigration, which shows the number of cases among the inoculated and the non-inoculated at Goalundo. From this table, it is seen that out of 1527 non-inoculated coolies, who passed through Goalundo, 33, or 2.09 per cent., got cholera; whereas of 873 inoculated coolies, only 2, or 0.2 per cent., were attacked by the disease; that is, the unprotected suffered about ten times as much as the inoculated. Assistant-Surgeon Mukerjee also reports that during his cold-weather tour he passed through some villages in the Manbhum district, in which he had practised inoculation the previous year: and, though there had been epidemics of cholera in them, the inoculated persons escaped. They came to him in numbers, stating that they owed their safety to the inoculation.”
Of course, the preventive treatment touches points only here and there on the map of India, with its 300,000,000 people. Probably it will never become so general in India as vaccination. Cholera in India recalls what Ambroise Paré, more than 400 years ago, wrote of the plague, “Here in Paris it is always with us.” But, wherever preventive inoculation has been done, there it has done good.
The Medical Annual for 1905 contains an account of some preventive inoculations recently made during an epidemic in Japan. Among the inoculated, the attack-rate was much lower than among the uninoculated; and the mortality was 45.5 per cent., as against 75 per cent.
Another most important result of the discovery of the cholera bacillus is its use in diagnosis. For example, if a case of suspected cholera is landed at a British port, the sanitary authority at once takes steps to ascertain whether the specific microbe is present; and, according to the answer given by bacteriology, either allows the patient to proceed on his journey, or adopts measures of isolation to prevent the spread of the disease to others. Thus, thanks to the insular position of Great Britain, this dreadful disease has for many years been prevented from invading her population.