Since in 1927 Dr Sensuke Izumi, former professor of pediatrics in Kanazawa Medical College (at present School of Medicine Kanazawa University) described a new children disease with rash which was similar to that of scarlet fever, sporadic cases and outbreaks of the disease were found in different places of Japan. It was called Izumi Fever in behalf of the name of the discoverer of the disease. As regards transmission route, waterborne infection was suspected. As far as the pathogenesis was concerned, several hypotheses were discussed among investigators. It was reported that certain virus was detected as a causative agent of Izumi Fever. However this report was not able to obtain general support. As the pathogenesis has not yet been clarified, the disease has disappeared since 1955; neither sporadic case nor outbreak was reported anywhere in the whole country. However, in 1981 after a long interval, an outbreak of Izumi Fever-like disease occurred in the Okayama Prefecture. Subsequently, cases and some outbreaks were reported in this area. What deserved notice regarding these recently reappeared diseases was the fact that the causative agent of these diseases was identified as Yersinia pseudotuberculosis. Now, whether the etiological agent of Izumi Fever which was before observed was Yersinia pseudotuberculosis or not, has been a new interesting topic. In this point of view, a special session for several papers of Yersinia infections was provided in the 60th Convention of the Japanese Society for Infectious Diseases, particularly in order to clarify the etiology of ancient Izumi Fever in relation to Yersinia infection. Four important papers which were presented in the session are published in this issue.
Experiments were performed and reviewed literatures about the isolation and serotyping of Yersinia pseudotuberculosis in Japan and epidemiology of human infection with the organisms. A total of 421 strains, 224 strains from human, 191 strains from 11 species of animals, 1 strain from pork and 5 strains from drinking waters, were examined. Latent infection is frequent in cattle, swine, dog, cat and rat, whereas monkey, goat, rabbit and guinea pig were diseased. The organisms were divided into 12 serovars. The most of strains belonged to serovar 4b, followed by serovars 3, 1b, 5b and 5a. The monthly prevalence of human infection was showed a higher incidence in colder months, November to May. Human infections with the organism were concentrated in 1 to 16 year old, with peak in the 1 to 3 year old. No relationship between serovar and sex-age incidence, and clinical manifestation was found. Some characteristics were noted about hosts and serovars of Y. pseudotuberculosis and age incidence of the infection in Japan compared with those of European countries.
Y. pseudotuberculosis infection in children was diagnosed in 164 patients by the isolation of the organism from stool samples and/or documenting the rise of serum agglutination antibody titer. Additionally Y. pseudotuberculosis was isolated from blood in 6 patients. Principal clinical findings were fever, rash, and abdominal symtoms. Other signs and symptoms were injected eyes, strawberry tongue, desquamation, erythema nodosum, common cold symtoms, liver dysfunction, and renal failure. The peak incidence of age was 2-years-old. This disease was rare in summer time. Diring recent two years of study, Y. pseudotuberculosis was isolated from drinking well or mountain water in 19% of the patients. Thease charactersitics were extremly mimicking to those of Izume fever, which occured in epidemics in Japan mostly after World War II. The etiology was not documented. Investigation was done in stocked sera from the patients of the epidemics of Izumi fever during last 10years. High antibody titers were documented in these sera. Present auther conclude the etiology of Izumi fevepidemics should be due to Y. pseudotuberculosis.
In March, 1986, an acute disease with symptoms suggestive of bacterial or viral origin occurred among two primary school children in Shishui Town, Chiba Prefecture. A total of 517 pupils and one teacher were affected. Major symptoms and signs of the patients were fever (100%), rash (77.8%), abdominal pain (73.6%), diarrhea (66.7%), nausea (62.5%), headache (55.6%), vomitting (54.2%), strawberry tongue (52.1%). Causative organisms were detected in 37 out of 92 patients. All isolated strains belonged to serotype 4b. Strains isolated from patients possessed about 40 Mdal plasmid and the results of calcium dependence and autoagglutination were both positive. There were no deaths and most of the patients recovered within a month.
The author reports mass-infection of Yersinia pseudotuberculosis 4B which occurred in two elementary schoold in Shisui in Chiba Prefecture in March 1986. A total of 548 children were infected, including 28 hospitalized children. There was no death, nor secondary infection. Fever, two-peak fever (40%; a type of recurrent fever which recurs after an intermittence of a few days following the first onset of fever), exanthema (primary, secondary and erythema nodusum), strawberry tongue, and gastrointestinal symptoms were noted as characteristic symptoms. In many of the patients, it took 2-3 weeks until the improvement. 30% of the patients were complicated with hepatic trouble, 8%(12 patients) with acute renalfailure and 8% with hematuria. In comparison between the disease and Izumi disease, no difference was noted. Six children had five or six of the six characteristic symptoms of Kawasaki disease (MCLS), which the MCLS Diagnostic Criterion defines as determinants of MCLS, but none of these 6 patients essentially came under the criterion. 2-DE was carried out in 31 children, whose findings were allnormal.
Sera of 802 children, aged 0 to 10 years, were collected at kawasaki city and the suburb during a period from 1978 to 1985, and neutralizing (NT) antibodies to varicella virus were examined for seroepidemiological study. The data obtained were analysed in age distribution, and in annual fluctuation. The results were as follows: 1) The positive rates of NT antibodies showed a tendency to increase with age, during the eight years, and it had been revealed that the rates in the groups of 0-3, 4-6 and 7-10 years old were 49.0, 70.8 and 88.8% respectively. 2) The positive rates of the groups, aged 3 to 6 years, showed higher in 1979 and 1983. The rates of the group, furthermore, in 1983 was significantly higher than those in other years, and a relationship between the high rates of NT antibodies in the groups and a number of varicella contraction was observed. 3) Persistent period of maternal NT antibodies of infants was approximately 6 or 7 months. 4) A maximum rate of varicella contraction was recognized in the groups of 5 years old, and it was considered that the most of all children might be primarily infected with varicella virus until 6-7years old. 5) An inapparent infection rate of varicella in the groups of 1-3, 4-6 and 7-10 years were 48.3, 58.7 nad 61.6% respectively.
Stools examination for intestinal protozoa in patients of traveller's diarrhoea were carried out in 1983 and 1984 (the 1st period), and in the period from July, 1985 to June, 1986 (the end period). Results obtained were as follow: 1) In the 1st period, stools from 1, 256 patients who had oversea travel over 5 days were examined. Seven species of intestinal protozoa, including 39 cases with Giardia lamblia, were detected (3.9%). 2) 98% of all the positive cases were the travellers over 10 days and 67.4% were travellers over 30 days. 3) An aparent seasonal variation was recognised in the positivity rate. 4) 92% of the positive cases with Giardia lamblia (1st period) visited India, 64% Thailand, 41% Nepal. More than 70% of Giardia lamblia positive cases among travellers to India or Nepal, stayed over 10 days in the respective countries. 5) In the 2nd period, stools from 178 patients who stayed in India and/or Nepal more than 10 days were examined. Three species of intestinal protozoa, including 25 cases with G. lamblia were detected (14.0%). 6) 64 cases with G. lamblia were summarizes though the 1st and 2nd periods of examination. In 29 cases among them, some species of pathogenic bacteria or other species of intestinal protoxoa were concomitanly detected. 7) The positivity rate of G. lamblia in travellers who stayed over 10 days in India and/or Nepal was 12.9% in 1983 and 12.2% in 1984, and not significantry different from that (14.0%) in the 2nd period.
Four hundred forty intravenous catheter tips and 167 blood samples obtained from patients suspected of intravascular catheter-associated fever were evaluated bacteriologically. Three hendred thirty-seven organisms were isolated from 224 out of 440 catheter tips (50.9%). Organisms isolated were 89 coagulase negative Staphylococci (CNS), 45 Enterococci, 44 Candida, 43 Staphylococcus aureus and 36 nonfarmenting Gram-negative Tod (NFGNR). Forty of 167 blood samples were positive with colonization of corresponding catheter tip and were confirmed as catheter-associated bacteremia. Organisms detected in both b000d and catheter tip were S. aureus 25.0%, Candida 25.0%, NFGNR 15.9%, P. aeruginosa 9.1%, CNS 9.1% and Enterobacteriaceae 9.1% each. Then, clinical feature of catheter-associated bacteremia were analized. The duration of indwelling intravenous catheter ranged from 3 to 41 (mean 15.4) days. Sudden onset of high fever and rapid resolution after the removal of the catheter were characteristic. Appropriate antimicrobial agents were administered in 57.9% of patients whose fever subsided within 3 days after the removal of the catheter, and in 60.0% whose fever were perisisted. However, inappropriate antimicrobial agents were administered in 6 of 8 patients died of septicemia within a month. Incidence of each organisms isolated from blood and catheter tip are different. For the treatment of catheter-associated bacteremia, removal of the contaminated catheter and appropriate choice of antimicrobial agent in regard to the implicated organisms such as S. aureus, Candida and NFGNR are essential.
Serological study of neutralizing (NT) antibody against Japanese Encephalitis virus was performed in non-affected district of Tokyo. In the group without vaccination, NT antibody was detected in 17 out of 62 sera (27%) below one year of age, 17 out of 87 (20%) in one to two years, and 10 out of 97 (10%) in two to three years. NT positive rate increased gradually up to 46%(6 out of 13 sera), in five to six years of age. In eight to ten years of age, including vaccine recipients, NT antibody was detected in 23 out of 30 (77%). NT positive rate showed approximately more than 80% over twenties and thirties, declining to 60% in fifties and sixties. The Kumamoto, JaGAr01, Beijing, and Nakayama-NIH strains of Japanese Encephalitis virus were employed for the comparative serological study. All NT positive sera obtained from children without vaccination revealed a high titer of NT antibody agaisnt Nakayama-NIH strain, and the titer against the Kumamoto strain was the lowest. In most NT positive sera, the NT titers against Nakayama-NIH strain were higher than those against the Beijing strain. These results demonstrate that Japanese Encephalitis virus is still prevailing even in Tokyo, and that the antigenicity of virus in Tokyo might closely relate to Nakayama-NIH strain. We should pay attention to a trend of Japanese Encephalitis virus epidemic, considering the recent extent of urbane sanitary conditions.
A long-term follow-up study was carried out after the injection of HB vaccine for children. Positive rate for anti-HBs showed 83.3% in the first year but decreased to 60.0% in the second year. Prevalence of high responder (Cut off index (C. I.) over 50) also decreased from 43.5% after 9 months to 21.7% after 2 years. Seronegative rate for anti-HBs in the second and third year were 30.3%(10 of 33) and 16.7%(1 of 6) respectively. These eleven seronegative cases had a low C.I. below 50 and particularly in 7 cases, C.I. was lower than 10. During the period of observation, there were 8 no and 8 low responders for vaccination, 3 cases with inapparent HBV infection; one from no responders and the remainders from non-vaccine group, and also a case with the elavation of anti-HBs alone probably due to the booster effect. These findings suggested the necessity of re-vaccination for no responders and the possibility of prevention against HBV infection for low responders.
Twenty six hybridoma clones which secrete monoclonal antibodies to Rickettsia tsutsugamushi, Gilliam, Karp and Kato strains, were produced by fusing mouse myeloma cell line P3X63Ag8.653 with spleen cells from BALB/c mice immunized with the rickettsial strains. In order to clarify the immunological characteristics of Rickettsia tsutsugamushi, reactivity of these monoclonal antibodies against the three strains was examined by immunofluorescent antibody test. The results obtained are as follows: 1) Ten clones produced Gilliam strain specific antibodies. 2) Three clones produced Karp strain specific antibodies. 3) Three clones produced Kato strain specific antibodies. 4) Five clones produced antibodies which reacted to Karp and Kato strains, but not to Gilliam strain. 5) Five clones produced antibodies which reacted to Gilliam, Karp and Kato strains. Reactivity of these monoclonal antibodies against Irie strain was examined by immunofluorescent antibody test. And it was clarified that Irie strain was Gilliam-Kato type. Analysis by polyacrylamide gel electrophoresis and immnuoblotting experiments revealed that Rickettsia tsutsugamushi has over 30 bands, including major bands corresponding to molecular sizes of 61 kilodaltons (K) and 46K when samples for electrophoresis were dissolved at 21°C for 15 hours, and including major bands corresponding to molecular sized of 61K and 60K when samples were dissolved at 100°C for 5 min. Immunoblotting experiments with the monoclonal antibodies against each strain demonstrated the 61K, 60K, 46K and 44K proteins showed antigenic activities. The 60K and 46K proteins appeared to be strain specific antigen, whereas 61K and 44K proteins to be common antigens of Rickettsia tsutsugamushi. A major polypeptide which showed strain-specific antigenicity appeared at the 46K position in samples solubilized at 21°C for 15 hours but moved to the 60K position in samples heated at 100°C for 5minutes. The finding suggests this strain specific antigen is a heat modifiable protein. But a major polypeptide which showed common antigenicity appeared at the 61K position samples solubilized at 21°C for 15 hours did not move after samples were heated at 100°C for 5 minutes.
The effect of norfloxacin (NFLX), a new quinolone agent, was compared with that of pipemidic acid (PPA) on infectious enteritis (bacillary dysentery, Campylobacter enteritis and enteropathogenic E. coli enteritis etc.) by a double-blind method. NFLX was administrated orally in a dose of 600mg/day, and PPA was administrated orally, 2, 000mg/day. The duration of the treatment was five days. Of 227 cases studied, 68 cases were excluded from analysis of effectiveness. The effectiveness was evaluated in 159 cases; 80 reveived NFLX and 79 reveived PPA. There was no statistical significance beteeen NFLX group and PPA group in terms of the background characteristics and MIC distribution for each drug. The results obtained were as follow: 1. NFLX group was as same as PPA group in clinical effect judged by docters in charge. There was no significnat difference between both groups in defeverscence, disappearance of blood stool, decrease in number of defecation and improvement of stool character. 2. In bacillary dysentery, the bacteriological effect of NFLX (100%) was superior to that of PPA (88.9%). Days required for eradication of organisms for NFLX group were shorter than those for PPA group with significant difference in Shigella spp. 3. No subjective side effect was observed in both groups. Slightly abnormal laboratory findings were seen in 11 cases of NFLX group and 7 cases of PPA group. 4. On clinical usefulness judged by the docters the ratio of usefulness were 100% in NFLX group and 86.0% in PPA group with significans difference in bacillary dysentery. From these results, NFLX is considered to be very useful medicine in the treatment of patients with infectious enteritis or carriers.