Upon these observations the Calcutta municipality felt encouraged to vote funds for the continuance of the inoculations in an experimental farm, and appointed for that purpose a special staff. In 1896 the result of two years’ observations were embodied by the health officer in a report to the Calcutta Municipal Corporation. It recorded a most satisfactory state of affairs. During the time under observation some eight thousand persons were inoculated. Cases of cholera occurred in seventy-seven huts in which some members of the family had been previously inoculated and others not. Comparing the incidence of the disease in the two groups, a striking advantage was found to be with the inoculated. I made an analysis of the cases according to the time which had elapsed between inoculation in each of these huts and the occurrence of cholera in them, and the following results were found. During the first four days after inoculation, apparently before the vaccine had time to produce its full protective effect, there were proportionately 1.86 times fewer deaths among the inoculated than among the non-inoculated members of the families. In a second period, extending from the fifth to the four hundred and twenty-ninth day—i. e., for fourteen months—there were 22.62 times fewer deaths among the inoculated; while in the last period—that is, between the four hundred and thirtieth and seven hundred and twenty-eighth day after the inoculation—there were only 1.54 fewer deaths among the inoculated, the immunity having evidently gradually disappeared. The net result was that for two years after inoculation, including the periods of incomplete protection, there was a reduction in mortality of 72.47 per cent among the inoculated; or in other words, in houses in which inoculations were performed and in which cholera subsequently occurred there were, even from the day of inoculation, before the full effect of it could be produced, eleven deaths among the non-inoculated to only three among the inoculated. Eight lives out of every eleven were saved.
At the end of my first cholera campaign, in August, 1895, there were altogether 31,056 natives of India, 125 Eurasians, 869 Europeans of the civil population, 6,627 native officers and sepoys, and 294 officers with 3,206 men of the British troops stationed in India, in all 41,787 people, who had submitted to inoculation. Observations instituted among them, especially among prisoners, soldiers and coolies in tea estates, with regard to whom detailed records could be kept, went to confirm the results as detailed above. In order to lengthen, if possible, the period of immunity, the plan was formed of inoculating stronger vaccines and in higher doses. The inoculations are now carried on in a Government laboratory, in Purulia, Bengal, chiefly among the people emigrating to the cholera districts of Assam, and there is no doubt that in the course of time a marked effect upon the prevalence of cholera in those districts will be produced and valuable theoretical data will be obtained.
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There was one noticeable feature about the results of the inoculation against cholera which early attracted my attention, and this was that while the number of attacks and the absolute number of deaths was strikingly influenced by the operation, the proportion of deaths to those attacked did not appear to be changed. The case incidence was effectively checked, but the ‘case mortality’ was not reduced. The inoculation diminished the chances of an attack of cholera—that is, the chances of the cholera virus penetrating into the tissues of a man; but if it so happened that the patient was attacked and the virus found an entrance and started growing in the system notwithstanding the inoculation, the latter would not assist in mitigating the severity of the symptoms or reducing the fatality of the disease. In analyzing this result further, it seemed to me permissible to assume that the vaccine protected against the cholera microbes themselves, but did not protect against their poisonous products, which are the cause of the actual symptoms.
This interpretation of the facts found support in a set of laboratory experiments by Professor Pfeiffer and Dr. Kolle, of Koch’s Institute, in Berlin, who showed that the blood serum of animals and persons inoculated with the cholera vaccine, as practiced in India, acquired an intense power of destroying cholera microbes, but exhibited no properties capable of counteracting the effect of their toxic products—no ‘antitoxic properties’. Combined with those of previous experimenters these results tended to prove that two kinds of immunity could be produced separately, and it became incumbent to devise a plan which would secure not only a lowering of susceptibility to the disease, but also a reduction in the case mortality.
For that purpose it seemed rational to attempt the treatment with a vaccine containing a combination of bodies of microbes, together with their toxic products. I intended to test this plan experimentally in the cholera districts; but, plague having broken out in Bombay, the Government of India commissioned me to inquire into the bacteriology of that disease, and I determined that the knowledge gained in the cholera inoculations should be applied and tested in the preparation of a prophylactic against the new epidemic.
The experiments I had in view involved manufacturing a material on a large scale, and operating on it for weeks continuously. To do this it was essential to find a way of recognizing plague growth with certainty, so as to enable the officers engaged in the manufacture to control the process and know exactly when they were handling the proper stuff, and when an admixture and invasion of extraneous growth took place. When this was solved, a drug was prepared by cultivating the plague microbe in sterilized broth, to which a small quantity of clarified butter or of cocoanut oil had been added. The plague bacilli attach themselves to the drops of butter or oil floating on the surface, and grow down into the depth of the liquid, forming a peculiar threadlike appearance. While doing so they secrete toxic matter, which is gradually accumulated in the liquid; at the same time a large amount of microbial growth comes gradually down from the surface of the liquid and collects at the bottom of the flask. When shaken up the whole represents the desired combination of the bodies of microbes and of their toxic products. The process is continued for a period of five to six weeks. As the microbes of plague had been very little studied before, and as their exact effect on the human system was unknown, I decided not to use for the treatment living microbes, but to use at least at first ‘carbolized’ vaccines, though the result of the treatment might be less favorable or less lasting than that which could be expected from living vaccines. The microbes in the above plague growth were accordingly killed by heating them at a temperature ranging from 65° to 70° C., and then mixed with a small proportion of carbolic acid, to prevent the drug from subsequent contamination and decomposition. The dose of the prophylactic was regulated by measuring up the quantity to be injected. The requisite amount is determined by the degree of fever which it produces. The febrile reaction varies in different individuals, but a temperature reaching 102° and above in at least thirty per cent of those inoculated has been found to indicate a good material. In the cholera, rabies and smallpox vaccines, the microbes being employed in a living state, it was essential to fix the strength of the vaccine, for otherwise it was impossible to predict the behavior of the microbe when injected into the system. In the case of the plague prophylactic the activity of the microbes is arrested before it is inoculated, and the effect can be regulated, as mentioned above, by simply measuring up the doses in the same way as is done with any chemical drug.
The expectation formed when devising the plan for the plague prophylactic has been very fortunately justified, and an advance on the results from the cholera vaccines was obtained; but I can not yet say certainly whether this favorable result is indeed due to the particular provisions which I had made for obtaining it.
The effect of the plague prophylactic was first tested at the Byculla Jail, in Bombay, when the epidemic reached that establishment. From the first day after the inoculation till the end of the outbreak there were in the jail twelve cases and six deaths among one hundred and seventy-two uninoculated inmates, and two cases, with no deaths, among one hundred and forty-seven inoculated. A year later, almost exactly a similar result was observed when the plague attacked the so-called Umarkhadi Common Jail, in Bombay. In this case after the inoculation there were ten cases and six deaths among one hundred and twenty-seven uninoculated inmates, and three cases, with no deaths, among one hundred and forty-seven inoculated. These and other observations show that the vaccine for the plague begins to exercise its effect within some twenty-four hours after inoculation; that it is useful even in the case of persons already infected; that it is therefore applicable at any stage of an epidemic. Numerous further observations were soon collected on the working of the system.
At the small village of Uudhera, of the Baroda feudatory state, where plague broke out, inoculation was applied to a half of each family, the other half remaining uninoculated. After that there were twenty-seven cases and twenty-six deaths among sixty-four uninoculated, and eight cases, with three deaths, among seventy-one inoculated of the same households, the proportionate difference in mortality being over eighty-nine per cent. There followed observations on a far larger scale, demonstrating that the mortality of the inoculated, compared to that of the non-inoculated, was on an average between eighty and ninety per cent less. Sometimes this reduction reached ninety per cent. In the Punjaub, in a village called Bunga, there occurred, in two hundred and eighty-one not inoculated, ninety-seven cases of plague and sixty-five deaths, while among seventy-four inoculated there were six cases, but no deaths. In Bangalore, among 80,285 of the inhabitants not inoculated, there were 2,208 deaths from plague, while among 23,537 inoculated there were only 108. The observations at Lanowli, Kirkee, Daman, Hubli, Dharwar, Gadag, in the Bombay Presidency, gave the same results. At Hubli over forty-two thousand inhabitants out of some fifty thousand were inoculated. In Bombay city, out of a population of 821,764, 157,256 have now undergone the inoculation. The work proceeds here at present at the rate of one thousand to eleven hundred inoculations a day.