Delaying the third dose of Japanese aluminum-free hepatitis A vaccine Aimmugen elicits effective immune responses against hepatitis A in adults.

Inactivated aluminum-adsorbed hepatitis A vaccines such as Havrix, Vaqta, and Avaxim are commonly used worldwide. These vaccines are typically administered in a two-dose series (at 0 and 6-12 months). However, a lyophilized inactivated aluminum-free hepatitis A vaccine, Aimmugen, which is approved in Japan, is typically administered in a three-dose series (at 0, 2-4, and 24 weeks). Hence, individuals visiting endemic hepatitis A areas receive the primary two doses of Aimmugen before traveling and the third booster dose much later. It is currently uncertain whether boosting with a delayed third dose of Aimmugen is effective, or whether a new vaccination schedule should instead be initiated. Therefore, we investigated the anti-hepatitis-A viral immune response of adult travelers who received the third dose of Aimmugen more than 24 weeks after the first dose. Participants were vaccinated with the third dose of Aimmugen more than 2 years after the first two doses. Antibody titers were measured at Day 0 (prevaccination) and at 28-42 days after the third dose of Aimmugen. Twenty-nine adult participants were enrolled in the study (14 men and 15 women; mean age ± standard deviation age, 36.2 ± 8.1 years). The interval between the first two doses and the third dose was 3-14 years. The seroprotection rate (i.e., the percentage of participants with anti-hepatitis A virus antibody titers ≥ 10 mIU/mL) was 96.6 % (28/29) at Day 0 and increased to 100 % (29/29) at Days 28-42. Geometric mean concentration increased from 105 to 4,013 mIU/mL. We demonstrated that delaying the third dose of Aimmugen still elicited effective immune responses after priming with two doses of the vaccine. Trial registration: UMIN Clinical Trials Registry (UMIN-CTR): MIN000013624. Registered 03 April 2014. https://center6.umin.ac.jp/cgi-bin/ctr/ctr_view_reg.cgi?recptno=R000015906.

Immunogenicity of Catch-Up Immunization with Conventional Inactivated Polio Vaccine among Japanese Adults.

Most Japanese adults are vaccinated twice with the Sabin trivalent oral polio vaccine. Booster vaccination is recommended for Japanese travelers to polio-endemic/high-risk countries. We assessed the catch-up immunization of healthy Japanese adults aged ≥20 years with two doses of standalone conventional inactivated polio vaccine (cIPV). Immunogenicity was evaluated by serum neutralization titers (pre-booster vaccination, 4-6 weeks after each vaccination) against type 1, 2, and 3 poliovirus strains. The participants were 61 healthy Japanese adults (26 men/35 women; mean age ± standard deviation age 35.8 ± 8.0 years). Seropositivity rates (percentage of participants with anti-poliovirus antibody titers ≥1:8) pre-vaccination were 88.5%, 95.1%, and 52.5% for Sabin strains (type 1, 2, and 3); 72.1%, 93.4%, and 31.1% for virulent poliovirus strains (type 1: Mahoney; type 2: MEF-1; and type 3: Saukett); and 93.4%, 93.4%, 93.4%, and 88.5% for type 2 vaccine-derived poliovirus strains (SV3128, SV3130, 11,196, and 11,198). After one cIPV dose, all seropositivity rates increased to 98.4-100.0%. After two cIPV doses, the seropositivity rates reached 100% for all strains. cIPV was well tolerated, with no safety concerns. Catch-up immunization with standalone cIPV induced robust immune responses in Japanese adults, indicating that one booster dose boosted serum-neutralizing antibodies to many strains.

A Guide for Businesses and Employers Responding to Novel Coronavirus disease (COVID-19): 4th edition.

The Japanese Society of Travel and Health (JSTH) and the Japanese Society for Occupational Health (JSOH) have compiled "Novel Coronavirus Information" together as a joint document, which has been shared with the public on their respective websites since February 2020. In May 11, 2020, this document was to be published as "A Guide for Businesses and Employers Responding to Novel Coronavirus Disease (COVID-19)" (hereinafter referred to as "this Guide"). This Guide was prepared for persons in charge of COVID-19 control measures in their workplace. It should be used at the discretion of each business operator according to their workplace environment. The examples of infection control measures shown in this Guide are not guaranteed to work for all situations, and they do not limit or bind actual measures being put in place. When selecting actual measures, it is necessary to obtain new information and thoroughly understand individual cases and situations. This Guide was prepared based on findings and reports about the virus and response measures taken by the relevant ministries (Ministry of Health, Labour and Welfare, Ministry of Foreign Affairs, etc.) that could be confirmed as of December 15, 2020. Therefore, the contents of this Guide may need to be modified in the future, depending on changes in the situations mentioned above. In the preparation of this Guide, every effort has been made to ensure the accuracy of currently obtainable information. However, neither JSTH or JSOH shall be held liable for any unfavorable circumstance, such as loss and damage (including lost profits and various expenses), harmful rumors, etc. experienced by a business operator, his/her employees, and any other persons concerned as a result of various measures considered/implemented using this Guide by persons responsible for infection control in the workplace.

A Safety and Immunogenicity Study of a Single Dose of a Meningococcal (Groups A, C, W, and Y) Polysaccharide Diphtheria Toxoid Conjugate Vaccine (MEN-ACWY-D) in Healthy Japanese Participants.

Meningococcal disease can cause significant disability and mortality. The quadrivalent meningococcal polysaccharide diphtheria toxoid conjugate vaccine (Men-ACWY-D) protects against invasive meningococcal disease caused by serogroups A, C, W, and Y. This phase III, open-label, single-arm, multicenter study evaluated the safety and immunogenicity of a single vaccine dose in healthy Japanese adults. The study enrolled 200 participants between 2 and 55 years of age. Immunogenicity was assessed by quantifying the seroprotection rates (the proportion of participants with antibody titers ≥ 1:128 against the capsular polysaccharide from all 4 serogroups measured 28 days after vaccination). Safety endpoints included occurrence, nature, time to onset, duration, intensity, relationship to vaccination, and outcome of solicited and unsolicited adverse events (AEs) and serious AEs (SAEs). Participants included 194 adults, 2 adolescents, and 4 children. Among adults, the seroprotection rates for serogroups A, C, W, and Y were 91.2%, 80.2%, 89.1%, and 93.8%, respectively. Seroconversion rates (the proportion of participants with pre-vaccination titers of < 1:4 and a ≥ 4-fold rise from baseline) were 87.3%, 83.0%, 94.4%, and 96.4%, respectively. No immediate AEs, adverse reactions, SAEs, or deaths were reported for any age group. Men-ACWY-D is well tolerated and immunogenic, eliciting antibodies against capsular polysaccharides from all 4 serogroups in Japanese adults.

Immunogenicity of aluminum-adsorbed hepatitis A vaccine (Havrix®) administered as a third dose after primary doses of Japanese aluminum-free hepatitis A vaccine (Aimmugen®) for Japanese travelers to endemic countries.

BACKGROUND: Hepatitis A vaccination is recommended for travelers to endemic countries. Several inactivated aluminum-adsorbed hepatitis A vaccines are available worldwide, but only one licensed hepatitis A vaccine is available in Japan. This vaccine is a lyophilized inactivated aluminum-free hepatitis A vaccine (Aimmugen®). The standard schedule of Aimmugen® is three doses (at 0, 2-4 weeks, and 6 months). Japanese people will go abroad after receiving 2 doses of Aimmugen®. Some long-term travelers will receive the third dose of hepatitis A vaccine at their destination, at 6-24 months after 2 doses of Aimmugen®. Aimmugen® is not available in countries other than Japan. They receive inactivated aluminum-adsorbed hepatitis A vaccine instead of a third dose of Aimmugen®. This study was undertaken to determine whether the booster vaccination with an aluminum-adsorbed hepatitis A vaccine is effective following two doses of Aimmugen®. METHODS: Subjects were healthy Japanese adults aged 20 years or older who had received two doses of Aimmugen®. Subjects received a booster dose of Havrix®1440 intramuscularly as the third dose. Serology samples for hepatitis A virus antibody titers were taken 4-6 weeks later. Anti-hepatitis A virus antibody titers were measured by an inhibition enzyme-linked immunosorbent assay. RESULTS: Subjects were 20 healthy Japanese adults, 6 men and 14 women. The mean age ± standard deviation was 37.2 ± 13.3. The seroprotection rate (SPR, anti-hepatitis A virus antibody titer ≥10 mIU/mL) was 85% at enrollment, and increased to 100% after vaccination with Havrix®. The geometric mean anti-hepatitis A virus antibody titer increased from 39.8 mIU/mL to 2938.2 mIU/mL. CONCLUSION: The three scheduled doses consisting of two doses of Aimmugen® plus a third dose with Havrix® is more immunogenic than using only two doses of Aimmugen®. The vaccination with Havrix® could be allowed to be used instead of a third dose of Aimmugen®. (UMIN000009351).

A retrospective survey of dengue fever among Japanese individuals staying in Manila, Philippines.

Dengue fever is a serious concern for Japanese people staying in Southeast Asia. In order to implement necessary prophylactic measures for dengue fever in this population, we investigated the characteristics of dengue fever among Japanese nationals living in Manila, Philippines. From 2012 to 2015, 175 Japanese expatriates were diagnosed with dengue fever at the medical clinic of the Japanese Association Manila, Inc. Most of the patients were employees of Japanese companies and their families and were long-term residents of Manila. Most patients were either <10 years or in their 30s to 40s. Two patients (1.1 %) were diagnosed with dengue hemorrhagic fever. No deaths due to dengue fever were reported. The reported number of patients with dengue fever has shown a decreasing trend: from 55 cases in 2012 to 53 in 2013, 31 in 2014, and 36 in 2015. The results of this survey could be useful for the development of effective dengue fever preventive measures such as health education and provision of information among not only Japanese but also other foreigners residing in endemic areas.

Characterization of a human isolate of Tritrichomonas foetus (cattle/swine genotype) infected by a zoonotic opportunistic infection.

Tritrichomonas species flagellates (IMC strain) were isolated from the biliary tract of an individual who had developed cholecystitis as a complication of acquired agammaglobulinemia. Sequence analysis of Tritrichomonas sp. (IMC clone 2 (cl2)) was performed for several genetic regions including the ITS1-5.8S rDNA-ITS2 region, the cysteine protease (CP)-1, CP-2 and CP-4 to CP-9 genes, and the cytosolic malate dehydrogenase 1 gene. In addition to comparison of the variable-length DNA repeats in the isolate clone with those in T. foetus (Inui cl2) and the T. mobilensis (U.S.A.: M776 cl2) reference strains, this analysis showed that the Tritrichomonas sp. (IMC cl2) was T. foetus (cattle/swine genotype). Injection of T. foetus (IMC cl2) directly into the livers of CBA mice resulted in liver abscess formation on Day 7. Moreover, inoculation via orogastric intubation caused infection in the cecum on Day 5 in CBA mice co-infected with Entamoeba histolytica (HM-1: IMSS cl6). T. foetus (IMC cl2) was able to grow in YI-S medium for over 20 days, even at 5°C. These results indicate that the T. foetus isolate is able to survive in the feces and edible organ meat of the definitive host for a prolonged period of time, and it is possible that the parasite could infect humans.

A Japanese study to assess immunogenicity and safety of a typhoid Vi polysaccharide vaccine.

BACKGROUND: Although typhoid fever is rare in Japan, imported cases have been reported occasionally in travelers returning from endemic areas. To achieve licensing of a typhoid Vi polysaccharide vaccine (Typhim Vi(®)) and make it widely available in Japan, this study was conducted at the request of the Japanese Ministry of Health Labor and Welfare to assess the immunogenicity and safety of this vaccine when given as a single dose (the recommended schedule of administration) in a Japanese population. METHODS: In this multi-center, open-label, non-comparative, intervention study performed in Japan, 200 healthy volunteers (188 adults [≥ 18 years of age], 7 adolescents [12-17 years of age] and 5 children [2-11 years of age]) were administered Typhim Vi(®). Immunogenicity was assessed 28 days after vaccinations using an ELISA method of anti-Vi antibody detection. A 4-fold increase in anti-Vi titer was considered as the threshold for seroconversion for anti-Vi antibodies. Safety was assessed up to 28 days following vaccination. RESULTS: Overall, 92.0% (95% confidence interval [CI]: 87.3-95.4%) of participants achieved seroconversion 28 days after a single dose of typhoid Vi polysaccharide vaccine. GMTs of Vi antibody titers increased from 6.6 (95% CI: 5.8-7.4) prior to vaccination to 157.3 (95% CI: 135.1-183.2) on Day 28 after vaccination. The geometric mean of individual anti-Vi antibody titer ratios (Day 28/Day 0) was 23.9 (95% CI: 20.3-28.3). There were no immediate adverse events and no adverse events led to the discontinuation of participants from the study. Across all age groups, pain and myalgia were the most frequently reported injection site and systemic reactions, respectively. Most of these reactions were mild in intensity and resolved within 7 days. CONCLUSIONS: A single dose of typhoid Vi polysaccharide vaccine, Typhim Vi(®), demonstrated good safety and immunogenicity profile in a Japanese population.

Present situation and challenges of vaccinations for overseas travelers from Japan.

The vaccination rates of Japanese people travelling abroad are still relatively low compared to travelers from Europe and the U.S. The following 3 causes are considered to contribute to the low vaccination rates among Japanese. First point is the lack of attention to the prevention of diseases during overseas travel in Japanese people. Second point is the limited number of healthcare facilities where Japanese overseas travelers can receive vaccinations. Third, many vaccines administered to travelers are still unapproved in Japan. However, there appear to be recent developments in each matter. With these social changes, the vaccination rate should be improved by disseminating recognition of the importance of the travel medicine in Japan. This report summarizes the present situation of vaccination of Japanese overseas travelers and discusses the challenges to improving vaccination rates.

Past, present and future of travel medicine in Japan.

At present, more than 17 million Japanese travel overseas annually, and one out of seven Japanese now travel abroad. Accordingly, an increasing number of these travelers contract diseases, but the practice of travel medicine is not common in Japan yet. However, travel medicine societies and the like have been established in Japan since the late 1990s, and Japanese medical professionals are becoming increasingly interested in this field of medicine. In this paper, the past, present and future of travel medicine in Japan is reviewed.

[The prevalence of Enterobius vermicularis among Japanese expatriates living in developing countries].

Parasitic infections are widespread in developing countries. Enterobiasis, caused by the Enterobius vermicularis nematode, is probably the most common helminth infecting the humanrace. We studied fecal specimens from Japanese residents in developing countries to determine the prevalence of E. vermicularis infection in this population. Individual specimens were collected using the cellophane tape method from Japanese residents in Asia, the Middle East, East Europe, Africa, and Central and South America in 2004. The specimens were examined in Japan. Subjects surveyed numbered 2247. The E. vermicularis infection rate was 0.62%. The most children infected with E. vermicularis ranged between 5 and 8 years of age. The prevalence of infection among Japanese children living in developing countries was 1.82%, higher than that in those living in Japan. Our results underscore the need to continue preventive measures such as health education to eradicate E. vermicularis infection in this group.

[Traveler's vaccine use among Japanese expatriates in developing countries].

Traveler's vaccinations are recommended for preventing infectious disease among overseas travelers. Focusing on Japanese expatriate adults residing in developing countries, we report our results for 2002 and 2005 vaccination status. Positive responses to the statement "Had traveler's vaccination before leaving Japan" increased from 49.9% in 2002 to 55.8% in 2005. Regionally the vaccination rate was high among those traveling in South Asia and Tropical Africa, and vaccination rates high in all regions for hepatitis A and B and tetanus. Vaccinations rates for rabies, yellow fever, Japanese encephalitis, and polio, were high in regions where these are known to be specifically prevalent. A certain number of travelers in some regions had also been vaccinated against typhoid and meningococcal meningitis although these vaccinations are not authorized in Japan. Despite these positive developments, however, much work remains to be done to raise the awareness among Japanese expatriates in developing countries of the need for vaccinations.

Early detection of Schistosoma mansoni infection by touchdown PCR in a mouse model.

A detection assay for Schistosoma mansoni DNA in mouse serum samples based on touchdown PCR was developed and evaluated. The serum samples could be assayed directly without the need to extract DNA. No cross reactions between S. mansoni and related species inducing human schistosomiasis were observed. After the infection, mouse sera and feces were collected for 8 weeks. Anti-worm antigen IgG and anti-soluble egg antigen IgG were detected in the sera at 6 weeks post-infection by ELISA. The parasite's eggs were detected in the feces at 8 weeks. In contrast, S. mansoni DNA was detected in the sera at 2 weeks post-infection. These data suggest that touchdown PCR is a potential tool for the early diagnosis of S. mansoni infection.

[Changes in the prevalence of intestinal parasites among Japanese expatriates in developing countries].

In order to study the prevalence of intestinal parasites among Japanese expatriates of developing countries, we conducted fecal specimen examinations annually from 1995 to 2000. Fecal specimens were collected from Japanese expatriates of each area: Asia, the Middle East, East Europe, Africa and Latin America. The specimens were fixed with 10% formalin in the local area, and then examined in Japan. We used the formalin-ether sedimentation method to find protozoan cysts or helminth eggs. In 1995, the infection ratio was 3.0% (N = 981), decreasing to 2.4% (N = 1,275) in 1996, 2.3% (N = 1,620) in 1997 and 1.6% (N = 1,574) in 1998. However, the ratio began to increase in 1999 (2.0%, N = 1,713) and 2000 (2.5%, N = 1,806). The ratio in Africa was the highest in each year, followed by Asia and Latin America. Heterophyidae (51 cases), Giardia lamblia (42) and Trichuris trichiura (30) were detected most frequently. In Egypt, the ratio of Heterophyidae rose by 28.8% in 2000. This was the prime reason for the increase in the overall ratio of infections worldwide. Most of the Japanese infected with Heterophyidae in Egypt had ingested dried mullet roe. This may explain the reason for the increase in the infection ratio there. Although the prevalence of intestinal parasites among Japanese expatriates in developing countries is decreasing, those who eat fish in these areas are still at risk. In order to eradicate intestinal parasitosis from this group, we must continue preventive measures such as health education.

Antibody responses induced by immunization with a Japanese rabies vaccine determined by neutralization test and enzyme-linked immunosorbent assay.

The immunogenicity of a Japanese purified chick embryo cell culture rabies vaccine (PCECV) was examined. Serum samples were obtained from 86 subjects after pre-exposure or post-exposure prophylaxis. Rabies antibody titres were determined by neutralization test and enzyme-linked immunosorbent assay (ELISA). Titres higher than 0.5 international units (IU)/ml were demonstrated by neutralization test in all the 19 subjects after three-time pre-exposure immunization on days 0, 30 and 180. Titres higher than 0.5IU/ml were also demonstrated by neutralization test in all the 23 subjects after four-time post-exposure immunization on days 0, 3, 7 and 14. There was a correlation between neutralization and ELISA antibody titres (r=0.697); however, neutralization titers were higher than ELISA titres for most of the samples. The results suggest that current Japanese rabies vaccine induces recommended levels of neutralizing antibodies after pre- and post-exposure prophylaxes.