Smallpox patients have been extremely rare in our country in recent years, and still less have we a chance to-day to observe a mass incidende of the disease. These circumstances have made us to regard our own experiences in epidemiological and clinical surveys more notewothy, which we performed in Mukden for several years before the end of the war. What interested us most from the epidemiological point of view, was the favourable effect of vaccination, and the study was concentrated to emphasize the difference between the vaccinated and the unvaccinated.
1) Epidemiological investigations revealed that the incidence rate of smallpox among the vaccinated was below 1/10 of that of the unvaccinated. For the comparison of the severity of disease the index of variola types (V.T.I.) was calculated, which was determined by variola vera+variola haemorrhagica/variola without exanthema+variola mitigata×10.
This gave a low value of 4.4 for the vaccinatd, while that of the unvaccinated was 295.0. As a matter of course there was a considerable difference in the case mortality rate between both groups, that of the vaccinated being only 5.6% in contrast with a high figure of 53.5% of the unvaccinated.
2) The development of clinical symptoms, subjective as well as objective, was in every respect less remarkable in the group of the vaccinated. The prodromic exanthema, characteristic to the vaccinated, was observed in 47.5 to 69.0% of the vaccinated patients. It predicted generally a mild course of the disease, with the exception of purpuric exanthema, which, though occurring extremely rarely, meant always a serious prognosis, and was attributed to a very insufficiently acquired immunity. The presence of such cases, though very rare, indicated the necessity of more radical vaccination.
3) Serious prognosis was suggested, when the nuclear index of neutrophilic leukocytes gradually fell with the progress of the disease, accompanied by neutropenia. In the unvaccinated, remarkable leukocytosis was induced by uniform increase in every type of leukocytes, almost without any change in the percentage, while in the vaccinated an initial leukopenia, caused by a decrease of lymphocytes and neutrophilic leukocytes, preceded leukocytosis, which was brought about by an increase of lymphocytes. The initial reduction of lymphocytes and neutrophilic leukocytes, though unexplained in its cause, was of practical importance in differentiating smallpox from other similar diseases.
4) The modification or alleviation of clinical features of smallpox by the vaccination, as described in 1)-3), was augmented by repeated vaccinations and when the time elapsed since the vaccination was short. The clinical manifestations of the disease were slight in such cases, and this was naturally ascribed to well developed immunity.
In such a country as Manchuria, where smallpox was endemic, the necessity was realized by the author to execute the vaccination at least once a year immediately prior to the season of prevalence, that is, in December and January, especially in view of the distinguished preventive effect of vaccination. It was further regarded to be of utmost importance to generalize the vaccination among the Manchurian and Korean inhabitants. In Japan the rate of effectual vaccination at the first period prescribed by law is 100%, that at the second period just before the school age 90-99% and at the third period at the completion of the primary course it is not less than 50-70%. Because the vaccination is seldom performed except on the three occasions prescribed by law, and the effect of the vaccination can hardly be expected to last beyond 2 or 3 years, the immunity of the total population against smallpox must be highly insufficient. They are accordingly exposed to an explosive mass incidence of severe smallpox, in the event of coming into, contact with the virus, which may be introduced from foreign countries.

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Experimental studies were performed to examine the effect of inhibition of TCA-cycle to bacterial infection. The male mice of pure strain, weighing 11.5 to 12.5 grams, were employed throughout the study. The 24 hour culture filtrate of dysentery bacilli on a semisynthetic medium was injected in the caudal vein of the animals, and 0.1cc of malonate solution, containing 10mg of disodium malonate, was injected intraperitoneally once an hour for successive five hours. The symptoms and the survival rate of the animals were observed.
The culture filtrate of Sh. flexneri 2a (Ew.10) and Sh. sonnei (Ew.33), injected in a dosage of 0.2cc which was not lethal for the untreated animals, caused death of the malonate treated animals with convulsion. The same dosage of the culture filtrate of E. coli and S. typhi murium hardly caused death even in the malonate treated animals. On the other hand, the suspensions of bacteria, alive or dead, had an approximately unif orm lethal effect on the malonate treated animals, despite the variety of bacterial species described above, and the lethal dosis was 1/10 to 1/12 of that with the untreated animals. Culture medium itself had of course no harmful effect on the malonate treated animals. It was concluded therefore, that the toxic substance contained in the culture filtrate of dysentery bacilli, represented some metabolic product of the bacteria, other than endotoxin. Further investigations revealed that the toxic substance was related neither to histamine nor to tyramine.
The toxicity of the culture filtrate of dysentery bacilli was influenced by the composition of the media. The most remarkable toxic effect was confirmed with the medium containing casein hydrolysate in a low concentration of 100-500mg/l and glucose in a concentration of 0.1%. The toxic effect of the culture filtrate was not proportional to the degree of bacterial growth. It remained unchanged when heated to 100°C for 30 minutes, but was destroyed by heat of 115°C in 10 minutes. It was inactivated by the addition of a certain amount of ATP to the culture filtrate.
On the mice, in which TCA-cycle was inhibited either by sodium fluoracetate or by sodium arsenite, instead of sodium malonate, the culture filtrate of dysentery bacilli had likewise a remarkable lethal effect, which was not =firmed with other bacteria.

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