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.

Refractory pharyngeal ulceration due to cytomegalovirus in a patient with HIV infection: a case report and literature review.

BACKGROUND: Cytomegalovirus (CMV) is an important pathogen among immunocompromised hosts. Typically, CMV in human immunodeficiency virus (HIV) infection causes diseases of the retina, digestive tract, lungs and liver, but there are few cases of CMV infection of the pharynx and larynx. CASE PRESENTATION: A 57-year-old man with HIV infection was admitted because of pharyngeal pain. Before and after admission, pharyngeal biopsies guided by laryngeal endoscopy were performed four times, but pathological examination showed nonspecific inflammation, and the cause of pharyngeal ulceration was unclear. Additionally, the ulceration deteriorated after initiation of retroviral therapy. Laryngomicrosurgery was conducted under general anesthesia to remove tissue, and pathological diagnosis confirmed CMV infection. Pathological features included enlargement of the cytoplasm and nucleus in infected cells, and intranuclear bodies called owl's eye inclusions. Ganciclovir dramatically improved the symptoms and laryngoscopic findings. CONCLUSIONS: This case was diagnosed as pharyngitis and pharyngeal ulceration caused by CMV infection, related to immune reconstitution inflammatory syndrome. In previous reports of CMV-induced pharyngeal or laryngeal ulceration in HIV infection, we found six cases similar to our present case. All cases were diagnosed by biopsy. The present case indicates the importance of biopsy for definitive diagnosis. CMV infection should be considered as a differential diagnosis of pharyngeal ulceration in patients with HIV infection.

The Seasonality of Peripheral Venous Catheter-Related Bloodstream Infections.

INTRODUCTION: Although the seasonality of infectious diseases has been widely reported, the seasonality of peripheral venous catheter-related bloodstream infection (PV-CRBSI) has not been investigated. This study investigated the seasonality of PV-CRBSI and its relationship with meteorological conditions. METHODS: A retrospective cohort study of PV-CRBSI at Tokyo Medical University Hospital (Tokyo, Japan), from 2009 to 2019, provided the data for descriptive and time series analyses used to evaluate the number of PV-CRBSI cases per 1000 admissions that occurred each month for each causative organism. By performing univariate and multivariate analyses, the researchers investigated the seasonality of cases and the relationships between meteorological conditions, other external factors, and PV-CRBSIs. RESULTS: This study included a total of 184 PV-CRBSI cases. The mean numbers of PV-CRBSI cases per 1000 admissions caused by all organisms, Bacillus cereus, Gram-positive cocci, and Gram-negative rods were 0.67, 0.15, 0.37, and 0.16 per month, respectively, during the study period. The time series analysis showed that the incidences of PV-CRBSI cases associated with B. cereus and Gram-negative rods were significantly different in the winter/spring from those in the summer/autumn (P < 0.05). The incidence of PV-CRBSI cases caused by B. cereus peaked during summer. The incidence of PV-CRBSI cases caused by B. cereus was significantly positively associated with average monthly temperature, whereas the incidence of PV-CRBSIs caused by Gram-negative rods was significantly negatively associated with average daylight hours. CONCLUSION: The incidence of PV-CRBSIs caused by B. cereus showed seasonality, peaking during the summer, and a significant correlation was found between PV-CRBSIs caused by B. cereus and average monthly temperature.

Regulatory aspects of quality and safety for live recombinant viral vaccines against infectious diseases in Japan.

Recombinant viral vaccines expressing antigens of pathogenic microbes (e.g., HIV, Ebola virus, and malaria) have been designed to overcome the insufficient immune responses induced by the conventional vaccines. Our knowledge of and clinical experience with the new recombinant viral vaccines are insufficient, and a clear regulatory pathway is needed for the further development and evaluation of recombinant viral vaccines. In 2018, the research group supported by the Ministry of Health, Labour and Welfare, Japan (MHLW) published a concept paper to address the development of recombinant viral vaccines against infectious diseases. Herein we summarize the concept paper-which explains the Japanese regulatory concerns about recombinant viral vaccines-and provide a focus of discussion about the development of recombinant viral vaccines.

Scenario-based simulation health care education for performance of hand hygiene.

BACKGROUND: Simulation health care education is widely used in medical education and has great potential. However, scenario-based simulation health care education for preventing health care-associated infections has not been described. METHODS: A single-center, prospective cohort study was conducted at Tokyo Medical University Hospital (1,015 beds), an acute care teaching hospital, from January 2011 to December 2014. Each training course was held every month and lasted 2 hours. Trainees put on and removed personal protective equipment under scenarios of standard precaution (2 scenarios) and contact precaution with methicillin-resistant Staphylococcus aureus (1 scenario), while considering the timing of hand hygiene. We determined the correlations between the participation rate in the simulation education and the use of alcohol-based hand disinfection and reduction of catheter-related bloodstream infection. RESULTS: There were 1,077 trainees. The total participation rate for hospital staff, which increased gradually during the study period, was 76% by the end of the study. The overall correlation between the use of alcohol-based hand disinfection in the hospital and the course participation rate was significant (correlation coefficient, 0.97). An inverse correlation (-0.94) was observed for the relation between the training course participation rate and the incidence of catheter-related bloodstream infection. CONCLUSIONS: Our training course had a positive effect on hand hygiene. This study is the first effective scenario-based simulation health care education on hand hygiene and control of health care-associated infection.

A Consensus on Immunization Recommendations for Healthcare and Other Workers at the Tokyo 2020 Olympic and Paralympic Games: A Delphi Survey.

This study aimed to build a consensus on recommendations of immunity requirements for vaccine-preventable diseases among healthcare and non-healthcare workers, including volunteers, at the Tokyo 2020 Olympic and Paralympic Games. We used a two-round Delphi method with a group of 17 Japanese medical doctors involved in vaccination or public health administration. We asked them to rank the importance of immunity to each vaccine-preventable disease as mandatory, recommended, considered if possible, or standard precautions only. The response rate was 88.2% (15/17) for the first questionnaire and 100% (17/17) for the second. All respondents considered that immunity to measles, rubella, varicella, mumps, and hepatitis B should be mandatory for healthcare workers, and 15 of 17 respondents considered that immunity to influenza should also be mandatory. Seven, three, two, and two respondents thought that immunity to pertussis, meningococcal disease, diphtheria, and tetanus should be mandatory, and ten, 11, seven, and seven thought it should be recommended. For non-healthcare workers, immunity to measles, rubella, and varicella was considered mandatory by 17, 15, and 15 respondents. Ten and eight respondents thought that immunity to mumps and influenza should be mandatory, and seven thought that it should be recommended. In conclusion, the consensus was that immunity to measles, rubella, and varicella should be mandatory for both healthcare and non-healthcare workers. Immunity to mumps, hepatitis B, and influenza was also considered mandatory for healthcare workers. Further discussions may be needed to develop a consensus on other vaccine-preventable diseases, especially if vaccination is not routine for adolescents or adults in Japan.

A Case of Conjunctival Ulcer and Uveitis Caused by Acrophialophora Sp. in an Immunocompromised Patient: a Case Report and Riterature Review.

We report the first case of invasive ophthalmologic infection by Acrophialophora sp. that was successfully treated using voriconazole (VRCZ). Acrophialophora spp., which has been reported to be an opportunistic pathogen, is a rare thermotolerant soil fungus, but its pathogenicity remains unclear. A 77-year-old man had neutropenia and prostate carcinoma and was receiving hemodialysis. His right eye had been infected for 2 days. His conjunctiva was congested, and it partially formed an abscess. Liposomal amphotericin B (L-AMB) was administered following systemic itraconazole. However, the treatment was changed from L-AMB to systemic VRCZ and VRCZ eye drops because his eye symptoms worsened. Subsequently, his symptoms stabilized and his vision was maintained. Acrophialophora sp. was identified by analyzing regions of internal transcribed spacer and domain 1 and 2 of the ribosomal RNA gene. He completed the 7-week systemic VRCZ course. The mean minimum inhibitory concentration of VRCZ for Acrophialophora spp. has been reported to be the lowest among various antifungal agents, and our results indicated the efficacy of VRCZ treatment for Acrophialophora sp. infection. Our results suggest that invasive Acrophialophora sp. infection may require long-term therapy. Further analysis of the clinical spectrum of Acrophialophora spp. infection and adequate treatment methods are required in the future.

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.

Bacille Calmette-Guérin (BCG) spondylitis with adjacent mycotic aortic aneurysm after intravesical BCG therapy: a case report and literature review.

BACKGROUND: Although intravesical bacille Calmette-Guérin (BCG) therapy is accepted as an effective treatment for bladder cancer, serious complications may occur in rare cases. To date, only 4 cases have been reported in which the patient developed a combination of mycotic aortic aneurysm and BCG spondylitis. Accurate diagnosis of BCG spondylitis is important because it is an iatrogenic disease, and its treatment is different from usual tuberculous spondylitis. However, distinguishing BCG spondylitis from usual tuberculous spondylitis is very difficult and takes a long time. In this study, we were able to suspect BCG spondylitis at an early stage from the result of the interferon-gamma release assay (IGRA). CASE PRESENTATION: We encountered a case of BCG spondylitis with adjacent mycotic aortic aneurysm after intravesical BCG therapy in a 76-year-old man. We performed a 2-stage operation to obtain spine stabilization and replace the aneurysm with a synthetic graft. We started multidrug therapy with antituberculosis medication, excluding pyrazinamide, because the patient's history of BCG therapy, negative IGRA, and positive of tuberculosis-polymerase chain reaction (Tb-PCR) suggested that the pathogenic bacteria of the spondylitis was BCG. Eventually the bacterial strain was identified as BCG by PCR-based genomic deletion analysis. CONCLUSIONS: BCG infection should be considered in patients who have been treated with BCG therapy, even if the treatment was performed several months to several years previously. In the case of a patient with a history of BCG therapy, a positive Tb-PCR result and negative IGRA result probably suggest BCG infections, if the possibility of false-negative IGRA result can be excluded.

Exploring Attractiveness of the Basic Sciences for Female Physicians.

In Japan, traditional gender roles of women, especially the role of motherhood, may cause early career resignations in female physicians and a shortage of female researchers. Besides this gender issue, a general physician shortage is affecting basic science fields. Our previous study suggested that female physicians could be good candidates for the basic sciences because such work offers good work-life balance. However, the attractiveness for female physicians of working in the basic sciences, including work-life balance, is not known. In a 2012 nationwide cross-sectional questionnaire survey, female physicians holding tenured positions in the basic sciences at Japan's medical schools were asked an open-ended question about positive aspects of basic sciences that clinical medicine lacks, and we analyzed 58 respondents' comments. Qualitative analysis using the Kawakita Jiro method revealed four positive aspects: research attractiveness, priority on research productivity, a healthy work-life balance, and exemption from clinical duties. The most consistent positive aspect was research attractiveness, which was heightened by medical knowledge and clinical experience. The other aspects were double-edged swords; for example, while the priority on research productivity resulted in less gender segregation, it sometimes created tough competition, and while exemption from clinical duties contributed to a healthy work-life balance, it sometimes lowered motivation as a physician and provided unstable income. Overall, if female physicians lack an intrinsic interest in research and seek good work-life balance, they may drop out of research fields. Respecting and cultivating students' research interest is critical to alleviating the physician shortage in the basic sciences.

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).

Solitary pulmonary caseating granulomas: A 5-year retrospective single-center analysis.

Solitary pulmonary caseating granulomas (SPCGs) are a characteristic type of tuberculomas associated with infection with non-tuberculous mycobacteria (NTM) and other microbes; however, their significance remains unclear. The aim of the present study was to describe the clinical characteristics of patients with SPCGs in terms of diagnosis, presence of lung cancer and treatment status. A retrospective analysis of 17 immunocompetent patients with histopathologically confirmed caseating granulomas after undergoing video-assisted thoracoscopic surgery (VATS) was conducted at our center between 2011 and 2015. The patients comprised 10 men and 7 women with a mean age of 59.1±14.4 years. Of the 17 patients, 14 (82.4%) were asymptomatic and the lesions were discovered incidentally. In 2 patients the SPCGs were accompanied by a small satellite nodule (SPCG mean diameter, 16.2±5.1 mm). Mycobacteria, including Mycobacterium tuberculosis (11.8%), Mycobacterium avium (11.8%) Mycobacterium kansasii (23.5%) and other Mycobacterium spp. (5.9%), were isolated from 9 of the patients (52.9%). Concurrent lung cancer was present in 3 patients (17.6%). When microbial agents could not be isolated, the interferon-γ release assay was useful for diagnosis. Positron emission tomography was not found to be useful for differentiating SPCGs from lung cancer, or for differentiating tuberculomas from NTM pulmonary nodules (NTMPNs). NTMPNs in cases of SPCGs were diagnosed more frequently in men. The findings indicate that a course of observation may be sufficient for patients in whom an SPCG from NTM (NTMPN) is identified by VATS. However, the presence of concurrent lung cancer in certain cases indicates that malignancy should not necessarily be excluded, particularly in NTMPNs, and highlights the necessity of aggressive diagnosis by VATS.

Peripheral venous catheter-related bloodstream infection is associated with severe complications and potential death: a retrospective observational study.

BACKGROUND: The purpose of this study was to identify the clinical characteristics and outcomes of peripheral vascular catheter-related bloodstream infections (PVC-BSIs) and determine the risk of severe complications or death. METHODS: We performed a retrospective observational study from June 2010 to April 2015 at two regional university-affiliated hospitals in Tokyo. We studied the clinical manifestations, underlying diseases, laboratory results, treatment methods, recurrence rates, and complications in 62 hospitalized patients diagnosed with PVC-BSIs by positive blood cultures. RESULTS: The median time from admission to bacteremia was 17 days (range, 3-142 days) and that from catheter insertion to bacteremia diagnosis was 6 days (range, 2-15 days). Catheter insertion sites were in the arm in 48 (77.4%) patients, in the foot in 3 (4.8%) patients, and in an unrecorded location in 11 (17.7%) patients. Additionally, the causative pathogens were Gram-positive microorganisms in 58.0% of cases, Gram-negative microorganisms in 35.8% of cases, Candida spp. in 6.2% of cases, and polymicrobials in 25.8% of cases. Eight (12.9%) patients died within 30 days of their blood culture becoming positive. Patients who died of PVC-BSIs had a higher proportion of Staphylococcus aureus infection than patients who survived (odds ratio, 8.33; p = 0.004). CONCLUSIONS: PVC-BSIs are a significant cause of health care-associated infection. We observed cases of severe PVC-BSI requiring intensive and long-term care along with lengthy durations of antibiotic treatment due to hematogenous complications, and some patients died. For patients with PVC-BSIs, S. aureus bacteremia remains a major problem that may influence the prognosis.

First case report of infection due to Cupriavidus gilardii in a patient without immunodeficiency: a case report.

BACKGROUND: Cupriavidus gilardii is an aerobic, Gram-negative, glucose-nonfermenting rod that was first identified in 1999. Because of the difficulty in accurate species identification of C. gilardii, there are few case reports of infection caused by this organism. In previous reports, C. gilardii has been characterized as an organism with low pathogenicity that causes opportunistic infections. CASE PRESENTATION: We encountered a case of pacemaker-associated bloodstream infection caused by C. gilardii in a 90-year old woman without obvious immunodeficiency. We identified the isolates as C. gilardii by sequencing of the 16S rRNA gene. The patient was treated with removal of the lead and administration of antimicrobial agents. Because of the acquisition of antibiotic resistance during antibiotic treatment, the antimicrobial agent was changed during the course of treatment. CONCLUSIONS: To our knowledge, this is the first report of an infection caused by this organism in a patient without obvious immunodeficiency. Although the true pathogenicity of C. gilardii is unclear, the possibility that it exerts pathogenicity not only in persons with immunodeficiency but also in immunocompetent persons is suggested.

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.

Neurocysticercosis with Diplopia Responds Well to Albendazole.

We report a case of neurocysticercosis concurrent with taeniasis in a 31-year-old woman. The patient presented with a headache and diplopia. Oculomotor disturbances with a left adduction deficit were observed. Fundoscopy revealed papilledema. Additionally, computed tomography of the brain revealed more than 20 small cysts within the parenchyma, most of which were associated with ring enhancement. Moreover, serum antibody testing (Western blotting) for Taenia solium-cysticerci was positive. The patient received albendazole and corticosteroids, and progressive resolution of the neurological symptoms and papilledema was observed starting approximately three days after administration. This patient has been asymptomatic for more than one year.

Catheter-Related Bloodstream Infection Due to Lodderomyces elongisporus.

Lodderomyces elongisporus infrequently causes bloodstream infections and has been isolated from Asia and Mexico. We encountered a catheter-related bloodstream infection, which involved some risk factors, due to L. elongisporus masquerading as Candida parapsilosis. A 39-year-old man who received a total arch and thoracoabdominal aortic replacement was admitted with a diagnosis of aorto-esophageal fistula. After thoracic drainage for the aorto-esophageal fistula, a catheter-related bloodstream infection was diagnosed. Micafungin (100 mg/day) was successfully administered to treat the catheter-related bloodstream infection for 42 days in total. The bloodstream and catheter tip yeast was grown on Candida agar medium and produced dark green colonies indicating Candida albicans. We performed sequencing analysis using a GenBank BLAST search. The sequence of the internal transcribed spacer region was 99.9% identical with that of the type strain L. elongisporus. This yeast organism has frequently been technically mistaken for non-albicans Candida spp. Furthermore, the prognosis and risk factors of L. elongisporus infection remain unclear owing to the scarcity of reported cases. Catheter-related bloodstream infection caused by this organism has not been described to date.

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.