National Institute Of Infectious Diseases Research Articles

日本の周辺国で問題となっているウイルス感染症 ２．クリミア・コンゴ出血熱

Crimean-Congo hemorrhagic fever (CCHF) is an acute infectious disease caused by CCHF virus (CCHFV), a member of the family Bunyaviridae, genus Nairovirus. The case fatality rate of CCHF ranges from 10-40%. Because CCHF is not present in Japan, many Japanese virologists and clinicians are not very familiar with this disease. However, there remains the possibility of an introduction of CCHFV or other hemorrhagic fever viruses into Japan from surrounding endemic areas. Development of diagnostic laboratory capacity for viral hemorrhagic fevers is necessary even in countries without these diseases. At the National Institute of Infectious Diseases, Tokyo, Japan, laboratory-based systems such as recombinant protein-based antibody detection, antigen-capture and pathological examination have been developed. In this review article, epidemiologic and clinical data on CCHF in the Xinjiang Uygur Autonomous Region, compiled through field investigations and diagnostic testing utilizing the aforementioned laboratory systems, are presented. CCHFV infections are closely associated with the environmental conditions, life styles, religion, occupation, and human economic activities. Based on these data, preventive measures for CCHFV infections are also discussed.

Evaluation of public knowledge about influenza based on influenza hotline consultations

In 1999, the Ministry of Health, Labour and Welfare issued guidelines on prevention and control of influenza. These included recommendations for public education about influenza and promotion of vaccination among persons at high risk for complications from influenza. In response, several public education programs were implemented, including an "influenza hotline" that was established within the Infectious Diseases Surveillance Center, National Institute of Infectious Diseases. To assess the informational needs of callers about influenza and evaluate the impact of different communication modalities, we analyzed data from telephone consultations made to the "influenza hotline" and from a survey that was conducted among a subset of callers. During the influenza seasons of 2000-2001 to 2002-2003, there was an average of 2,230 callers to the "influenza hotline" each season, range 1,809-2,696. The majority (42.4%) of callers were women aged 30-39 years, which might reflect young mothers. The most frequently asked questions were about influenza vaccination of infants and young children. which accounted for 20.6% (1,501/7,295) of all vaccine-related questions during the four seasons. Questions about the number of recommended influenza vaccine doses was the second most frequently asked topic and comprised 17.8% (1,300/7,295) of all vaccine-related questions. Over the period 2000-2001 to 2002-2003, questions about the recommended number of influenza vaccine doses decreased among elderly callers, but not for callers aged < 60 years. The number of calls about the location of influenza vaccine clinics, availability of influenza vaccine, and vaccination of elderly person declined from 1999-2000 to 2002-2003. Of callers that were surveyed (N = 3,316) about where they received information about influenza, the most frequently reported sources were newspapers (47.7%), and the internet (26.2%). Internet use by callers showed differences among age groups. Only 2.4% of callers aged > or = 60 years reported receiving influenza information through the internet in contrast to 33.9% among callers aged < 60 years. Our study suggests a high public demand for information about influenza, especially by mothers regarding influenza vaccination of infants and young children, and recommended influenza vaccine doses for adults. To improve education of the public about influenza, multiple communication strategies should be utilized, including written information, and the internet.

Establishment of an analyzing method for a Japanese encephalitis virus neutralization test in Vero cells

We established a 50% plaque reduction analyzing method of neutralizing antibody for human serum to Japanese encephalitis virus (JEV) in Vero cells, called the ‘3 points least-squares regression method’ (3LSRM). Our method shows a high correlation with the chick embryo cell method (the current standard method for human serum), using the chart method established by the National Institute of Infectious Diseases of Japan, which is an equation made with retrospective data obtained with the 50% plaque reduction method as a standard measurement method for neutralizing antibody titers to JEV. Our new method is much simpler and more reliable than the current method in that it uses an established cell line, Vero cells, and its results are computed by the 3LSRM.

分子疫学的手法に基づいた食中毒の監視体制; パルスネットの構築

As the foods are stocked below freezing and widely distributed, a kind of food-borne outbreak which occurs in separate regions or in different time, so called "diffuse outbreak", has been found at the present day. Unless the outbreak is early recognized, the number of victims would increase. Some methods have been developed to analyze the relatedness of bacteria isolated from the patients of enteric infections. PFGE, pulsed-field gel electrophoresis, is one of the methods and powerful to discriminate the difference in nucleotide sequences among bacterial genomes. Availability of PFGE analysis is appreciated to examine the linkage of each incident of food-borne infections in epidemiological investigation. A PFGE network, PulseNet Japan, is now under construction among National Institute of Infectious Diseases, local Health Institutes and Ministry of Health, Labour and Welfare.

Anaphylaxis to gelatin-containing rectal suppositories

Background: Some children—though the number is few—have been sensitized with gelatin. Objective: To investigate the relationship between the presence of antigelatin IgE and anaphylaxis to gelatin-containing rectal suppository, we measured antigelatin IgE in the sera of the children with anaphylaxis. Methods: Ten children showed systemic allergic reactions, including anaphylaxis, to a chloral hydrate rectal suppository containing gelatin (231 mg/dose) that had been used as a sedative. These children's clinical histories and serum samples were submitted from physicians to the National Institute of Infectious Diseases during a 2-year period from 1996 to 1997. Results: Of the 10 children, 5 showed apparent anaphylaxis, including hypotension and/or cyanosis, along with urticaria or wheezing; 2 showed both urticaria and wheezing without hypotension or cyanosis; the other 3 showed only urticaria. All of the children had antigelatin IgE (mean value ± SD, 7.9 ± 8.4 Ua/mL). As a control, samples from 250 randomly selected children had no antigelatin IgE. These findings suggest that the 10 children's systemic allergic reactions to this suppository were caused by the gelatin component. Conclusion: Gelatin-containing suppositories must be used with the same caution as gelatin-containing vaccines and other medications. (J Allergy Clin Immunol 2001;108:1033-4.)

Further development of influenza surveillance in China and global impact on influenza control

Influenza surveillance is important both on a local and a global basis for several reasons. Information obtained from surveillance is critical for the development and support of control and prevention strategies in China. Influenza surveillance in China also has serious global implications. It is known that China has been a source of new influenza strains, which include both “antigenic drifted” and “antigenic shifted” strains. Over the past 10 years, many of the vaccine strains recommended by WHO originated in China. Some of the pandemic strains are also thought to have originated from China. WHO, in collaboration with Centres for Disease Control and Prevention, the US and National Institute of Infectious Diseases, Japan has provided technical and financial support to the Ministry of Health (MOH), China. Currently, provincial and municipal laboratories in 10 provinces are actively monitoring influenza viruses under the National Influenza Centre in Beijing. MOH, with technical assistance from WHO, is finalizing a National Influenza Surveillance Plan. Over the next 5 years, we can expect the number of surveillance laboratories to increase to as many as 20. An influenza disease surveillance system will also be established.

The importance of global influenza surveillance for the assessment of the impact of influenza

Morbidity and mortality associated with influenza have been recognized for years.However, the true burden of disease has been difficult to determine. Precise quantificationof morbidity and mortality therefore underlines the need for vigilant surveillance, and agreater need for virological confirmation of cases that do not exhibit typical clinicalmanifestations of influenza. Delayed identification of a new virus variant that may causeanother pandemic may be even more devastating than the 1918 pandemic.1. The global surveillance networkFor more than 50 years, the main objectives of the WHO global influenzasurveillance have remained the same. These objectives are to measure the impact ofthe disease by collection and analysis of epidemiological information on morbidity andmortality, and to anticipate future epidemics, and pandemics, by the collection andanalysis of influenza viruses [1]. Influenza activity is currently monitored both globallythrough the four WHO Collaborating Centres for Reference and Research forInfluenza, Centers for Disease Control and Prevention (CDC), Atlanta, USA; WHOCollaborating Centre for Reference and Research for Influenza, National Institute forMedical Research (NIMR), London, United Kingdom; WHO Collaborating Centre forReference and Research for Influenza, Melbourne, Australia; and the WHO Collabo-rating Centre for Reference and Research for Influenza, National Institute of InfectiousDiseases, Tokyo, Japan; and nationally through a network of 110 National Influenza

Infection with Chlamydia pneumoniae accelerates the development of atherosclerosis and treatment with clarithromycin prevents it in a murine model Sumito Oguchi, Toshio Kishimoto, Tadayoshi Nosaka, Ken Nagao, Katsuo Kanmatsuse. Department of Cardiology, Nihon University School of Medicine, Tokyo, Japan, Department of Viology, Laboratory of Rickettsia&amp;Chlamydia, National Institute of Infectious Diseases, Tokyo, Japan

Infection with Chlamydia pneumoniae accelerates the development of atherosclerosis and treatment with clarithromycin prevents it in a murine model Sumito Oguchi, Toshio Kishimoto, Tadayoshi Nosaka, Ken Nagao, Katsuo Kanmatsuse. Department of Cardiology, Nihon University School of Medicine, Tokyo, Japan, Department of Viology, Laboratory of Rickettsia&amp;Chlamydia, National Institute of Infectious Diseases, Tokyo, Japan

Preparing for the worst. The USA and Japan's preparations for a terrorist attack with chemical or biological weapons.

Biological weapons are not just topics for contemporary novelists but found their way into classical literature long ago. Shakespeare has Hamlet's father's ghost describe, ‘Upon my secure hour thy uncle stole, with juice of cursed hebona in a vial, and in the porches of my ears did pour the leprous distillment.’ (Act 1, Scene 5) Indeed, neither the act nor the accusation is new. Jews in Europe were accused of poisoning wells to cause plague in the Middle Ages. Japanese planes in World War II dropped plague‐infested fleas over Chinese cities and villages. Murder or terrorism with biological or chemical agents is not a far‐fetched scenario—it has been used before. Criminal cases in the USA include various uses of biological agents in the last decades. The Rajneesh Foundation used Salmonella bacteria in 1984 to poison ten restaurant salad bars in the city of The Dalles, OR, hoping it would influence an election in its favour. A separatist group calling itself ‘Republic of Texas’ used Botulinum , HIV and rabies in 1998 and 1999 to threaten judges. Three members were later charged with conspiracy to use weapons of mass destruction and the eldest, Johnnie Wise, was sentenced to 24 years in prison. In 1977, Diane Thompson, a nurse from Texas, was sentenced to 20 years for intentionally contaminating doughnuts with Shigella dysenteriae in order to achieve personal revenge. > In 1998 and 1999, a separatist group from Texas used Botulinum, HIV and rabies to threaten judges The particular risk of biological agents, when used as weapons, is their extreme uncontrollableness. An infectious agent can easily spread from the original victim to relatives or colleagues. Particularly at risk are the medical personnel who treat victims without knowing what kind of infection they are dealing with. More unpredictable are the number of people and …

Minimum estimated incidence in Japan of anaphylaxis to live virus vaccines including gelatin

We have previously found that most occurrences of anaphylaxis to live virus vaccines are caused by gelatin present in the vaccines as a stabilizer. After we published the evidence for the role of gelatin in anaphylaxis, vaccine manufacturers in Japan began to eliminate gelatin from live virus vaccines. In the present study, we tried to estimate its incidence before the gelatin elimination was started. Physicians and vaccine manufacturers submitted serum samples from children with anaphylaxis to measles, mumps, rubella or varicella vaccine to National Institute of Infectious Diseases (NIID) for 3 years from April 1994 to March 1997. Specific IgE to gelatin was assayed at NIID or two manufacturers by the CAP and ELISA methods. There were 44 children with life-threatening severe anaphylaxis (airway obstruction or anaphylactic shock) during the 3-year period, 41 of whom had anti-gelatin IgE. There were 64 children with mild anaphylaxis (without airway obstruction); 62 had anti-gelatin IgE. There were 100 children with only systemic cutaneous signs; 81 had anti-gelatin IgE. The estimates for the incidence of the severe anaphylaxis in 1994–1996 are: 6.84, 7.31, 4.36, and 10.3 cases per million doses of gelatin-containing measles, rubella, mumps, and varicella vaccines, respectively.

Recombinant bacillus Calmette-Guérin as a potential vector for preventive HIV type 1 vaccines.

In August 1997, the World Health Organization (WHO) and the Joint United Nations Programme on HIV/AIDS (UNAIDS) convened an expert working group to discuss current strategies for the development of HIV type 1 vaccines. Based on the recent findings of investigators from Japan's National Institute of Infectious Diseases (NIID) in Tokyo using recombinant bacillus Calmette-Guérin (rBCG) as a potential vectored vaccine for HIV, a recommendation was made that further work in this area is a priority. As a result, the working group reconvened in September 1998 to discuss the progress to date with this vaccine approach, as well as areas of related research to assess the feasibility of a BCG-vectored HIV vaccine. This report summarizes the discussions addressing the available scientific data on the potential use of rBCG as a vector for preventive HIV vaccines, the work necessary to move such candidate vaccines into Phase 1 clinical trials, and recommendations targeted at facilitating the long-term development of rBCG-vectored HIV vaccines.

A01 感染症研究所昆虫医科学部所蔵の蚊類標本

A01 感染症研究所昆虫医科学部所蔵の蚊類標本

Outbreak of Japanese spotted fever in the southeastern part of Awaji Island.

Since the first patient with Japanese spotted fever (JSF) was reported in 1984p, a number of cases have been reported in all parts of Japan. However, this disease frequently occurs on the Pacific coast of Honshu, showing an uneven distribution. In 1999, a nationwide survey by the Infectious Disease Surveillance Center reported 34 cases by December. The Yuzuruha mountain range in southern Awaji Island is an area in which Rickettsia japonica is endemic2), and one to three patients are diagnosed with JSF in our hospital every year. In 1999, 9 patients with JSF were serologically identified. Erythema was noted in all patients, but obvious lymph node swelling was observed in only one, and eschar was noted in only 3 patients. One patient had concomitant DIC. The specific antibody titer was measured using immunofluorescence with R. japonica YH strain-infected cells in the National Institute of Infectious Diseases and the Hyogo Prefectural Institute of Public Health, and showing significant increase of the specific antibody titer in all cases. The locations where patients had been infected were concentrated in the forest land of the southeastern part of Awaji Island. Six employees of one company who had worked together in the forest simultaneously developed the illness, exhibiting high fever and eruptions. These cases were known when clinically diagnosed cases were included (one had been serologically diagnosed with JSF). Thus, mass outbreaks are also noted. Among serologically diagnosed patients, 2 patients in 1998 and 4 patients in 1999 who developed the disease had all lived in the same area for 10 years or more, though they had various occupations and leisure activities. Considering that lifelong immunity is acquired after rickettsial infection, this result suggests that the high incidence of JSF is attributable not only to an expanded area of daily activity of humans, but also to the influence of vectors, namely, an expanded endemic area , increased degree of endemism, which may be due to the global warming. Therefore, public health measures seem to be necessary . Part of the area showing this high incidence is designated as a national park , so crop dusting to control pine weevils is not performed as it is in the surrounding areas, which may contribute to an abnormal number of ticks to serve as vectors. Since it is possible that people may be infected in Awaji Island and

Genetic Analysis of Wild Polioviruses towards the Eradication of Poliomyelitis from the Western Pacific Region

Since a laboratory network to eradicate poliomyelitis in the Western Pacific Region started in 1991, the Department of Virology II, National Institute of Infectious Diseases, has been functioning as a Regional Reference Laboratory. From 1992 to 1998, we examined 5453 stool samples collected from 3501 patients with acute flaccid paralysis in Cambodia, Vietnam, and Laos, and we isolated 392-type 1 and 10-type 3 wild polioviruses. As a result of the extensive immunization during this time in this area, the numbers of poliomyelitis cases by wild polioviruses have drastically decreased. In 1997, only nine type 1 wild polioviruses were isolated. Eight out of the nine cases were found in Cambodia, and one was in mid-Vietnam. Since then no wild polioviruses have been isolated in the Western Pacific Region for more than two years. A nucleotide sequence analysis of these 1997 isolates indicated that they all belonged to the same strain that has been prevailing in the Indochina area, suggesting the complete interruption of wild poliovirus transmission in the region.

Changes in seroepidemiological pattern of Helicobacter pylori and hepatitis A virus over the last 20 years in Japan.

The age groups most susceptible to infection and the mode of transmission of Helicobacter pylori (H. pylori) are not yet clear. To contribute to a better understanding of this disease, this study was undertaken to evaluate changes in the seroepidemiological pattern of H. pylori in a group of Japanese people over the last 20 yr sampled in 1974, 1984, and 1994 in comparison with that of the hepatitis A virus (HAV), which was used as a marker of the fecal-oral route of transmission. A total of 1015 serum samples were obtained from the National Institute of Infectious Diseases in Tokyo. All of these samples were from healthy persons aged 0-89 yr (442 male and 573 female; median age 35.6 yr), living in seven prefectures in the central part of Japan in 1974, 1984, and 1994. All serum samples were assayed for H. pylori IgG by means of enzyme-linked immunosorbent assay (ELISA). Further, anti-HAV antibodies were assayed by blocking ELISA in the same samples. We investigated the prevalence of H. pylori and HAV for all ages, and the positive rate of H. pylori for infants and children separately. The overall prevalence of H. pylori antibodies was 72.7% (CI 95%, 68.0-77.3) in 1974, 54.6% (CI 95%, 49.1-60.0) in 1984 and 39.3% (CI 95%, 34.1-44.4) in 1994. That of HAV was 57.7% (CI 95%, 52.5-62.8) in 1974, 41.7% (CI 95%, 36.3-47.0) in 1984, and 23.4% (CI 95%, 18.9-27.8) in 1994. The prevalence of both H. pylori and HAV was found to increase with age, whereas there have been clear cohort shifts in the seroepidemiological patterns of both infections over the last 20 yr in Japan. This study shows that there is a slight similarity in the concordance of positive and negative populations between H. pylori and HAV. However, it was very difficult to determine the concordance between H. pylori and HAV infection in this study. Our data strongly suggest that the highest infection rates for both H. pylori and HAV occur among infants and children in Japan. This study provides evidence that H. pylori and HAV may share a common mode of transmission but that changes in environmental conditions make this very difficult if not impossible to prove with seroepidemiological data.

Changes in seroepidemiological pattern of Helicobacter pylori and hepatitis A virus over the last 20 years in Japan

OBJECTIVE: The age groups most susceptible to infection and the mode of transmission of Helicobacter pylori ( H. pylori) are not yet clear. To contribute to a better understanding of this disease, this study was undertaken to evaluate changes in the seroepidemiological pattern of H. pylori in a group of Japanese people over the last 20 yr sampled in 1974, 1984, and 1994 in comparison with that of the hepatitis A virus (HAV), which was used as a marker of the fecal-oral route of transmission. METHODS: A total of 1015 serum samples were obtained from the National Institute of Infectious Diseases in Tokyo. All of these samples were from healthy persons aged 0–89 yr (442 male and 573 female; median age 35.6 yr), living in seven prefectures in the central part of Japan in 1974, 1984, and 1994. All serum samples were assayed for H. pylori IgG by means of enzyme-linked immunosorbent assay (ELISA). Further, anti-HAV antibodies were assayed by blocking ELISA in the same samples. We investigated the prevalence of H. pylori and HAV for all ages, and the positive rate of H. pylori for infants and children separately. RESULTS: The overall prevalence of H. pylori antibodies was 72.7% (CI 95%, 68.0–77.3) in 1974, 54.6% (CI 95%, 49.1–60.0) in 1984 and 39.3% (CI 95%, 34.1–44.4) in 1994. That of HAV was 57.7% (CI 95%, 52.5–62.8) in 1974, 41.7% (CI 95%, 36.3–47.0) in 1984, and 23.4% (CI 95%, 18.9–27.8) in 1994. The prevalence of both H. pylori and HAV was found to increase with age, whereas there have been clear cohort shifts in the seroepidemiological patterns of both infections over the last 20 yr in Japan. This study shows that there is a slight similarity in the concordance of positive and negative populations between H. pylori and HAV. However, it was very difficult to determine the concordance between H. pylori and HAV infection in this study. CONCLUSIONS: Our data strongly suggest that the highest infection rates for both H. pylori and HAV occur among infants and children in Japan. This study provides evidence that H. pylori and HAV may share a common mode of transmission but that changes in environmental conditions make this very difficult if not impossible to prove with seroepidemiological data.

Ribotypes of clinical Vibrio cholerae non-O1 non-O139 strains in relation to O-serotypes.

The emergence of Vibrio cholerae O139 in 1992 and reports of an increasing number of other non-O1 serogroups being associated with diarrhoea, stimulated us to characterize V. cholerae non-O1 non-O139 strains received at the National Institute of Infectious Diseases, Japan for serotyping. Ribotyping with the restriction enzyme BglI of 103 epidemiological unrelated mainly clinical strains representing 10 O-serotypes yielded 67 different typing patterns. Ribotype similarity within each serotype was compared by using the Dice coefficient (Sd) and different levels of homogeneity were observed (serotypes O5, O41 and O17, Sd between 82 and 90%: serotypes O13 and O141 Sd of 72; and O2, O6, O7, O11, O24 Sd of 62-66%). By cluster analysis, the strains were divided into several clusters of low similarity suggesting a high level of genetic diversity. A low degree of similarity between serotypes and ribotypes was found as strains within a specific serotypes often did not cluster but clustered with strains from other serotypes. However, epidemiological unrelated O5 strains showed identical or closely related ribotypes suggesting that these strains have undergone few genetic changes and may correspond to a clonal line. Surprisingly, 10 of 16 O141 strains studied contained a cholera toxin (CT) gene, including 7 strains recovered from stool and water samples in the United States. This is to our knowledge the first report of CT-positive clinical O141 strains. The closely related ribotypes shown by eight CT-positive strains is disturbing and suggest that these strains may be of a clonal origin and have the potential to cause cholera-like disease. Despite the low degree of correlation found between ribotypes and serotypes, both methods appears to be valuable techniques in studying the epidemiology of emerging serotypes of V. cholerae.

Therapeutic Effect of Antimicrobial Drugs against Experimental Infections Due to Yersinia pestis in Mice

Although there are effective antibacterial agents against plague, newer antibacterial agents have been developed which show more potent activity against other bacterial organisms, but have not been tested againstYersinia pestis. A strain ofYersinia pestis was selected (no. 22; National Institute of Infectious Diseases, Tokyo, Japan) that caused a systemic infection in mice.Y. pestis no. 22 was intraperitoneally inoculated into DDY-strain mice, and 13 oral or 6 injectable antibacterial drugs given to the infected mice at varying doses 1 and 24 hours after infection. Levofloxacin, sparfloxacin and ofloxacin were the most effective oral agents against the infection, and prulifloxacin and pazufloxacin were also effective but to a lesser extent. Also, gentamicin and arbekacin were the most potent injectable antibacterial agents againstY. pestis. These results suggest that there are several new drugs, both oral and injectable, which exert excellent in vivo antibacterial activity against a mouse infection model and may be useful for the clinical treatment of plague.J Infect Chemother 1998;4:16-19

Developmental therapeutics branch division of AIDS national institute of allergy and infectious diseases national institutes of health

Developmental therapeutics branch division of AIDS national institute of allergy and infectious diseases national institutes of health

Antiviral research branch enteric diseases branch national institute of allergy and infectious diseases national institutes of health

Antiviral research branch enteric diseases branch national institute of allergy and infectious diseases national institutes of health