Recently two tularemia organisms-like causative agents have been found one after another. While introducing them, the author describes here on recent tularemia.
1) Tularemia in Japan, so-called yato-byo, has been investigated again after the World War II since the new epidemics occurred in Fukushima and Chiba prefectures from 1948 to 1950.
Shozo Toda (1885-1961), the President of Kanazawa University the retired Professor of Kyoto University who was the best friend of H. Ohara (1882-1943), the discoverer of yato-byo, organized the research groups of “Studies on yato-byo” and then “Studies on the tick-borne diseases caused by bacteria in Japan” supported by the Grant from the Ministry of Education during 6 years from 1954 to 1959. He has promoted these studies generally all over Japan.
2) The author also explains here the recent epidemics occurring in the infected countries chiefly on the basis of the data offered by Olsufjev of the Gamaleya Institute, Moscow.
3) According to the new proposal made by Russian and American authorities Pasteurella tularensis and Past. novicida should be contained in a new genus Francisella. And there are two types of Francisella tularensis; the one is F. t. palaearctica of so-called Eurasian type and the another F. t. nearctica of so-called North American type. Olsufjev et al. further studied several Japanese strains isolated by the author and others and called them F. t. palaearctica var. japonica Rodionova.
4) Ecological or bionomical observations made by Russian workers are introduced here. It will give us some suggestion on the further studies of yato-byo
Additionally, two causative organisms resembling Past. tularensis were also introduced as follows. Past. novicida was isolated by Larson et al. of Rocky Mountain Laboratory (RML) from a dead muskrat in. Utah in 1950. Yersinia philomiragia was first isolated by W.I. Jensen of Brigham City, Utah in 1959 from a moribund muskrat and in 1960, Jellison, Owen and Bucker of RML found 4 more isolates from water there while looking more Past. novicida.

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Subjected to this report were a total 104 cases of 96 children and 8 adults living in Takatsuki city. Used as monovalent vaccine were two strains of live attenuated rubella viruses, RA27/3 and Cendehill-51, respectively; as bivalent vaccines, a conjugation of RA27/3 and one of measeles vaccines, i.e., inactivated one (K), live attenuated one (L) or further attenuated live one (CAM). K, L and CAM are products made in Osaka University. Ten out of total 104 had been found rubella antibody positive at the prevaccination tests, and 94 proved negative (HI antibody titer<8 folds). To the former, RA27/3 or Cendehill-51, and to the latter, RA27/3 alone (to 23 cases), Cendehill-51 alone (21), a conjugation of RA27/3 and K (27), RA27/3 and L (3) or RA27/3 and CAM (20) was administrated subcutaneously.
The results and conclusions were as follows:
1) Unpleasant clinical manifestations were none except for slight fever elevation for a short period in each two cases (about 10%) of RA27/3 and Cendehill-51 and somewhat higher (37.6C-39.4C) and longer (up to 4 days) fever elevation in the case of a conjugation, RA27/3 and CAM, which, however, seemed to be due to only CAM's influence.
2) Isolations of rubella viruses from pharyngeal swabs were successful in 3 cases out of attempted 18 vaccinees.
3) Serologically, familial infections from the vaccinees were not evidenced.
4) In initially HI negative 94 cases, 23 inoculated with RA27/3 alone were all (100%) found converted to positive one month after the inoculation, mean HI elevation being 1: 276.6. In 21 Cendehill-51 cases, 19 (90.5%) were converted, mean HI being 1: 92.5. Stronger antigenicity of the former was confirmable. The curves of HI antibody level were frequently followed in 16 cases (RA27/3, 5 and Cendehill-51, 11). Generally, a rise began about two weeks after the inoculation and a peak was reached after one more week or so. In initially HI positive cases, no booster effects were achieved by the vaccinations.
5) A conjugation of RA27/3 and usual measeles K-L vaccines proved effective no less than above mentioned two vaccines to rubella antibody rise, and also effective to measeles antibody rise. To the author's knowledge, this is the first report of this kind in this country.
6) An interesting phenomenon was also observed in conjugation use of RA27/3 and CAM. Out of 17 (initially antibody negative for both rubella and measeles), 8 cases run febrile course owing almost undoubtedly to CAM's influence. In these febrile cases, measeles HI was raised much higher (1: 361.4) than in afebrile ones (1: 74.6). Contrarily, rubella antibody went up much higher (1: 192.6) in afebrile cases than in febrile ones (1: 38.1). It gives rise to a speculation of CAM's interference with RA27/3.
7) In the long term (12-16 months) follow-up, no notable decrease of rubella antibody titers was encountered in almost all cases.

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In previously reported serological data of ours for rubella obtained from inhabitants of Matsue city and Oki Island, Shimane prefecture, in 1966-1967, it was desclosed that exposures to the viruses had already begun in the population of Matsue city since 1967. Another evidence of this was brought about when Watanabe reported a considerable number of clinical cases of that year among the city dwellers.
From March to July, 1968, the following year, there actually took form of epidemic mainly among primary school children in the city.
Virological and serological surveys were conducted mainly on patients from initial phase of the epidemic, and serological ones were on two primary school classes, women in pregnancy, and women of marriageable age.
The results were summarized as follows:
1) HI rise estimated in 9 patients (school children) at the initial stage of the epidemic, using paired sera, was all high enough (8 times or more) for the confirmation of their rubella infection. These data together with the virological ones were made use of as a foothold of symptomatological and epidemiological judgement through ensuing course of the epidemic.
2) Virus isolation was attempted in 14 patients (16 specimens) and succeeded in 8 out of 13 specimens of throat swabs, in one out of 3 of cerebrospinal fluids. It can be said from this that in oder to obtain high isolation rate, throat swabs should be taken at least within 5 days of illness. Cerebrospinal fluid of successful case was the one which was withdrawn at 25th day of illness.
3) Some sero-epidemiological surveys prior to and after the epidemic:
a) On pregnant women; HI antibody was measured twice in 44. Newly infected cases during the epidemic could not be discovered.
b) HI titers of 77 women of 15-17, all not married, of this city were contrasted with data obtained from women of corresponding age in several other cities. In all, almost 100% of them had had positive titers. No difference was observed.
c) On two primary school classes; The purpose was to estimate the latent infection rate. Of the two, one is the class from which patients massively broke out (25 out of 35), the other, only two patients occurred out of 38. The data on the former class showed almost 100% were infected. One of two patients of the latter class failed to show significant rise of HI titers, the clinical diagnosis being doubted. Two third of this class remained uninfected, the data tell. The virus communication seemed to need relatively heavy contacts. However, considerable portion of school children could be regarded as latent.
4) The details of the virus characteristics are to be published in another report.

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A series of 50 patients with acute or chronic urinary tract infections were treated with Rifampicin to make clinical evaluation of efficacy of the recently introduced antimicrobial agent and a parallel laboratory study was performed to assess the drug for antibacterial activity against various bacterial pathogens therein involved. In 4 of the 50 cases seminal fluid specimens were obtained and assayed for antimicrobial activity, of which the results indicate extremely low concentrations of the compound in the seminal fluid to have been yielded following oral administration.
The diagnoses in the 50 cases of the clinical study herein described included: acute cystitis (27 cases), acute pyelonephritis (15 cases), chronic cystitis (4 cases), chronic pyelonephritis (3 cases) and prostatitis (1case).
The dose ranged from 600 to 900mg a day, given in 3 or 4 divided doses; and the duration from 4 to30 days, the total dose the reby ranging up to 27gm.
Escherichia coli infection accounted for 80 per cent (40 cases) of all the 50 cases studied. The isolates displayed overwhelmingly the MIC values within the range of 25 to 125mcg/ml, the antibiotic susceptibility of E. coli isolates to Rifampicin being less marked than to AB-PC, SM, TC, CP and KM by one to two steps of the twofold serial dilution.
The treatment was reasonably effective in acute cases of urinary tract infections; the clinical response was good in 26 of the 38 cases of acute infections, fair in 9 cases and poor in only the remaining 3 cases; hence an effectiveness rate of 68.4 per cent. The patients with chronic infections, however, all failed to respond favorably to the Rifampicin therapy.
No significant differences in clinical response were observed between the group of patients receiving 600mg of Rifampicin daily and that of patients given 900mg a day. There were no complications of particular note, with the only exception of coloration (red) of the urine.

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Kanendomycin (KDM), a new antibiotic derived from Streptomyces kanamyceticus, was administrated orally to 70 patients who were sent to the Department of Legal Communicable diseases, Tokyo Municipal Bokuto Hospital under the diagnosis of Bacillary dysentery (BD) during the period from April to August, 1969. By the laboratory data they were later revealed as BD (18 cases), salmonellosis (S) (8), pathogenic coli (PC) infection (19), and acute febrile diarreal cases of unknown cause (AFD) (25). In all, 80 mg/kg/day of KDM, every 6 hours, 4 times a day, was given for successive 7 days from admission.
In sensitivity test, all strains were suppressed by 2mcg/ml KDM concentration except one strain of shigella by 10mcg/ml, and two strains of PC, one by 30mcg/ml and the other over 50mcg/ml.
Clinical observations: 1) Effects to fever: On an average, the body temperature was normalized within two days of medication in all diseases group. 2) to stool frequency: The frequency was normalized (two times a day or less) within 3 days in BD, 7 days in S, 6 days in PC infection, and 6 days in AFD. 3) to stool appearances: Blood and pus disappeared within 4 days in BD, 6 days in S, 4 days in PC infection, and 3 days in AFD. Mucus was still seen by the end of the first week in 60% in BD, 87% in S and complete recovery from mucus discharge needed almost 3 weeks in the both. The recovery was a little earlier in PC infection, and almost the same as BD or S in the case of AFD. 4) to eradication of the causatives: Bacillary discharge was halted within 3 days in BD, 4 days in S. Redischarge was seen in 13% of S at some time between the second week and the third week. The positive rate was decreased to 7-13% in the course of medication in PC infection, but rose again to 27% after the halt of medication.
Conclusively, the author feel justified in evaluating the antibiotic, KDM, as recommendable in the treatment of bacillary dysentery due to resistant strains to usual antibiotics, in view of its excellent eradicating effect to causative agents. An impression is that the longer medication would be advisable in the case of salmonellosis. There are still problems to be solved in the case of pathogenic coli infection.

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Because of recent prevalence (80-85%) of resistant shigella against usual antibiotics, it has become routine principle for most physicians to place antibiotics other than usual ones to dysenteric patients, particularly at the first scene on admission.
Moreover, it is common that a good portion among clinically diagnosed bacillary dysentery comprises several other intestinal infections such as pathogenic coli, salmonella or vibrio parahaemolyticus infection.
The drug or drug combination of choice to begin with in dysenteric patients, therefore, is desired to be 1) other than usual antibiotics and 2) effective not only to shigella but also to other intestinal pathogens such as mentioned above.
The author, as a member of a special study team on Aminosidin (AMSD), has had a clinical experience with AMSD and studied its efficacy in this line.
The methods and results were summarized as follows:
1) Forty eight patients admitted to Tokyo Municipal Ebara Hospital under the diagnosis of bacillary dysentery (later rediagnosed as bacillary dysentery (BD), 28, salmonellosis (S), 8 and vibrio parahaemolyticus infection (VP), 12) were treated with AMSD singly (in 15 BD, 5 S and 11 VP) and in combination with AB-PC (in 13 BD, 3 S and one VP). That such a combination was tried in this series was from the author's consideration, as published before in this journal (Vol.43 No.1), that a combination of poorly and easily absorbable antibiotic is worth trying.
2) In single use; 2g AMSD, every 0.5g 4 times daily in adult. In combination use; 1g AMSD and 1g AB-PC, each 0.25g, total 0.5g 4 times daily. Medication continued for 5 successive days.
3) Clinical observations: Generally, excellent results were obtainable either in single or in combined use. Eradicating effects to causatives were seen within one to two days in BD, one to four days in S and VP, respectively, with only two exceptions of transient redischarge in S. Meanwhile, rectoscopic pictures suggested the combination use would have been more effective, if any, in dysenteric ulcers. There found no side effects to deserve particular mentioning.
4) Conclusively, AMSD, singly or combined, is recommendable as the drug of first choice at the inception of the treatment of dysenteric patients.

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[in Japanese]

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