Vasovagal reactions after COVID-19 vaccination in Japan.

Coronavirus disease 2019 (COVID-19) vaccine administration started in February 2021 in Japan. As of December 2021, approximately 75% of the population aged ≥12 years had received two doses of vaccine. We conducted a study to investigate vasovagal reactions (VVR) after COVID-19 vaccination using data on adverse events following immunization. The crude reporting rate of VVR (cases/1,000,000 doses) after vaccination was 9.6 in all age groups combined, and was more frequent in the younger age groups: 28.6 and 37.2 in individuals aged 10-19 years and 20-29 years, respectively. In individuals aged 10-29 years, the rate was similar in males and females (33.0 and 34.2, respectively, p = 0.53); but was higher after dose 1 than after dose 2 (57.4 and 8.8, respectively, p < 0.001). Based on these results, caution needs to be exercised when vaccinating adolescents and young adults, especially with dose 1 of COVID-19 vaccines.

Diagnosis of Acute Gastroenteritis with Immunochromatography and Effectiveness of Rotavirus Vaccine in a Japanese Clinic.

Despite the well known effectiveness of two licensed live attenuated oral rotavirus (RV)-vaccines, Rotarix and RotaTeq, constant monitoring of vaccine effectiveness (VE) is essential considering the evolving power and reassortment capability of RVs. In this study, we detected RV, norovirus (NV) and adenovirus (AV) infections using immunochromatography (IC)-based kits in children with acute gastroenteritis (AGE) who attended a pediatric clinic in Kiryu city, Gunma, Japan during June, 2014-September, 2018. VEs were determined using a test-negative study design. Among 1658 AGE-children, RV, NV and AV were detected in 96 (5.8 %), 146 (8.8 %) and 46 (2.8 %) children, respectively. Interestingly, the distributions of infections were found to be associated with age and sex. Namely, RV infections were significantly higher in female (P=0.02) and in the 19-30 month age group children, while NV and AV infections predominated in the 13-24 month and 7-18 month age groups, respectively. The disease severity for RV and NV infections remained similar and significantly higher than that of AV infections. The VE of RV-vaccines was 49.8 % (95 % CI: 22.7 to 67.3 %) against all RV infections, which was increased up to 67.2 % (95 % CI: 35.3 to 83.4 %) against severe RV infections. RV-vaccinated children experienced less severe symptoms in RV-infections while non-RV AGE remained less serious for both RV-vaccinated and unvaccinated children. Finally, the prevalence of RV infection remained minimized (≤5.4 %) in this population since 2015. Thus, this study provided important information on distribution of major AGEs in young children and exhibited the effective role of RV vaccines in post-vaccine era.

Molecular detection of enteric viruses in the stool samples of children without diarrhea in Bangladesh.

A number of molecular epidemiological studies reported the detection of enteric viruses in asymptomatic children. The role of these viruses in an asymptomatic infection remains unclear. This study investigated the enteric viruses in the stool samples collected from children without diarrhea. Stool samples were collected during June to October 2016, from 227 children who lived in Matlab, Bangladesh. Seventeen enteric viruses, including rotavirus A, B, and C (RVA, RVB, and RVC), norovirus GI (NoV GI), norovirus GII (NoV GII), sapovirus (SaV), adenovirus (AdV), human astrovirus (HAstV), Aichivirus (AiV), human parechovirus (HPeV), enterovirus (EV), human bocavirus (HBoV), Saffold virus (SAFV), human cosavirus (HCoSV), bufavirus (BufV), salivirus (SalV), and rosavirus (RoV), were investigated by RT-PCR method. One hundred and eighty-two (80.2%; 182/227) samples were positive for some of these viruses, and 19.8% (45/227) were negative. Among the positive samples, 46.7% (85/182) were a single infection, and 53.3% (97/182) were coinfection with multiple viruses. The HCoSV was the most prevalent virus (41.4%), followed by EV (32.2%), NoV GII (25.6%), HPeV (8.8%), RVA (6.2%), AdV (5.7%), AiV (5.3%), SAFV (4.4%), and SaV (2.6%). Each of NoV GI, HAstV, HBoV, and BufV was detected at 0.4%. However, RVB, RVC, SalV, and RoV were not detected in this study. Phylogenetic analysis showed that diverse HCoSV species and genotypes were circulating in Bangladesh, and four strains of species A are proposed to be new genotypes. The data indicated that non-diarrheal Bangladeshi children were asymptomatically infected with wide varieties of enteric viruses.

Concurrent decreases in the prevalence of wheezing and Ascaris infection among 5-year-old children in rural Bangladesh and their regulatory T cell immunity after the implementation of a national deworming program.

INTRODUCTION: Epidemiological research on the prevalence of asthma and helminthic infections in various countries has led to the hypothesis that helminthic infections protect against asthma by suppressing the host's immune response. This study was conducted to elucidate whether decreased Ascaris infection following a national deworming program was associated with increased recurrent wheezing among rural Bangladeshi children and to test their anti-inflammatory immunity. METHODS: This nested case-control study was conducted from December 2015 to October 2016 in the rural service area of the International Centre for Diarrhoeal Disease Research, Bangladesh. Of the 1800 5-year old children randomly selected for the study, informed consent was obtained from the guardians of 1658 children. Data were collected using a semistructured questionnaire adopted from the International Study of Asthma and Allergies in Childhood and blood samples for the analysis of regulatory T (Treg) cell immune responses and the balance between Th1 and Th2 immunity in Ascaris infections. RESULTS: A total of 145 children were found to have wheezing, yielding a prevalence rate of 8.7%, which was significantly lower than the rate found in 2001 (16.2%, P < .001); Ascaris infection also decreased from 2001 to 2016. The 127 wheezing children who agreed to participate further were compared to 114 randomly selected never-wheezing children. Wheezing had a significant positive association with antibiotic use, history of pneumonia, parents' history of asthma, and Ascaris infection; children with Ascaris infection were twice as likely to have wheezing (adjusted odds ratio = 2.31, P = .053). Flow cytometry found no significant differences in the rates of Th1, Th2, and CD4 + CD25 + CD127low cells by the wheezing group. CONCLUSIONS: Ascaris infection had a positive rather than a negative association with wheezing and the rates of wheezing and Ascaris infections both decreased from 2001 to 2016. These findings undermines the hypothesis that such infections provide protection against asthma.

How the gut microbiome regulates host immune responses to viral vaccines.

The co-evolution of the microbiota and immune system has forged a mutually beneficial relationship. This relationship allows the host to maintain the balance between active immunity to pathogens and vaccines and tolerance to self-antigens and food antigens. In children living in low-income and middle-income countries, undernourishment and repetitive gastrointestinal infections are associated with the failure of oral vaccines. Intestinal dysbiosis associated with these environmental influences, as well as some host-related factors, compromises immune responses and negatively impacts vaccine efficacy. To understand how immune responses to viral vaccines can be optimally modulated, mechanistic studies of the relationship between the microbiome, host genetics, viral infections and the development and function of the immune system are needed. We discuss the potential role of the microbiome in modulating vaccine responses in the context of a growing understanding of the relationship between the gastrointestinal microbiota, host related factors (including histo-blood group antigens) and resident immune cell populations.

Alarming Situation of Spreading Enteric Viruses Through Sewage Water in Dhaka City: Molecular Epidemiological Evidences.

Global burden of acute viral gastroenteritis remains high, particularly in developing countries including Bangladesh. Sewage water (SW) is an important node to monitor enteric pathogens both in the environment and among the population. Analysis of SW in Dhaka city deems crucially important because a large number of urban-city dwellers live in Dhaka city, the capital of Bangladesh, under a constant threat of precarious sewerage system. In this study, we collected raw SW from five locations of Dhaka city every month from June 2016 to May 2017. It was concentrated with polyethylene glycol (PEG) and investigated for three major enteric viruses, rotavirus A (RVA), norovirus GII (NoV GII) and adenovirus (AdV) using polymerase chain reaction (PCR). Most of these SW samples collected from both hospitals and non-hospital areas yielded enteric viruses: 76% samples were positive for AdV, followed by 53% NoV GII and 38% RVA. Viral load was determined as much as 1 × 107 copies/ml for RVA and 3.5 × 103 copies/ml for NoV GII. Importantly, NoV GII and AdV that can affect people of all ages were predominated during monsoon also when SW overflows and spreads over a wide and crowded area. Genotypes G1, G2, G3, G8, and G9 for RVA, GII.4 for NoV, and type 41 for AdV were detected representing the current profile of circulating genotypes in the population. This study provides the first evidence of distribution of major diarrheal viruses in SW in Dhaka city which is alarming showing grave risk of impending outbreaks through exposure.

Detection of nineteen enteric viruses in raw sewage in Japan.

One-year surveillance for enteric viruses in raw sewage was conducted in Kansai area, central part of Japan from July 2015 to June 2016. The raw sewage was collected monthly from an inlet polluted pool and was concentrated by polyethylene glycol (PEG) precipitation. Twelve sewage samples were screened for nineteen kinds of enteric viruses by using RT-PCR method and further analyzed by nucleotide sequencing. Twelve enteric viruses were found in the investigative sewage samples. Rotavirus A and norovirus GI and GII with several genotypes were detected all year round. Interestingly, norovirus GII.17 (Kawasaki-like strain) and rotavirus G2 that caused the outbreaks in Japan last epidemic season were also found in sewage. Moreover, adenovirus, astrovirus, sapovirus, bocavirus, human parechovirus, enterovirus, Aichi virus, Saffold virus and salivirus were also detected. Enterovirus D68 was detected only in the same month as those of enterovirus D68 outbreak in Japan. The rotavirus B and C, hepatitis A and E viruses, human cosavirus, bufavirus and rosavirus were not detected in this surveillance. The study provides the information on the enteric viruses contaminated in raw sewage, which is valuable for risk assessment. Our results imply that the viruses detected in sewage may be associated with infections in the Japanese population.

Multiplex RT-PCR for rapid detection of viruses commonly causing diarrhea in pediatric patients.

Multiplex RT-PCR method using five sets of panel primers was developed for the detection of diarrheal viruses, including rotavirus A, B, and C, adenovirus, astrovirus, norovirus GI and GII, sapovirus, Aichi virus, parechovirus, enterovirus, cosavirus, bocavirus, and Saffold virus. The sensitivity of the method was evaluated and tested with 751 fecal specimens collected from Japanese children with acute diarrhea. Several kinds of viruses were detected in 528 out of 751 (70.3%) fecal specimens. Mixed-infection with different viruses in clinical specimens could also be effectively detected. The method proved to be reliable with highly sensitive and specific and useful for routine diagnosis. J. Med. Virol. 89:818-824, 2017. © 2016 Wiley Periodicals, Inc.

Evaluation of Immunochromatographic Tests and a New Enzyme Immunoassay for Detection of a Novel GII.17 Norovirus in Stool Samples.

A novel GII.17 norovirus (NoV), Kawasaki 2014, has spread to several regions of the world. Rapid and reliable diagnostic tests are needed for the detection of this new NoV variant. In this study,analytical sensitivity of 7 different immunochromatographic (IC) test kits (6 are on the market in Japan and one in Europe) was evaluated by means of confirmed GII.17 NoV-positive stool samples. The stool samples were also tested by a bioluminescent enzyme immunoassay (BLEIA). Real-time RT-PCR served as a reference (gold standard) method. Among the 7 IC kits, RIDA QUICK was the most sensitive, with the limit of detection of 107 copies/ml, whereas the limits of detection of the other IC kits ranged from 108 to 109 copies/ml. It should be pointed out that the limit of detection of BLEIA was approximately 100- to 1,000-fold better (104-105 copies/ml) than that of RIDA QUICK. Nevertheless, the procedure of BLEIA took more time and required sophisticated equipment.

Four-year study of viruses that cause diarrhea in Japanese pediatric outpatients.

Acute gastroenteritis continues to be a major public health problem worldwide. A wide variety of viruses associated with diarrhea disease is being reported continually. This study investigated the epidemiological situation of viruses that cause diarrhea in Japanese pediatric patients. This study enrolled a total of 2,381 fecal specimens collected between 2009 and 2013 from Japanese children with acute gastroenteritis. There is currently a 70.4% prevalence of viruses causing diarrhea among these Japanese pediatric outpatients. Norovirus was detected in 39.3% of the patients, whereas the prevalence of rotavirus, human parechovirus, enterovirus, adenovirus, sapovirus, astrovirus, and Aichi virus was 20.1, 6.6, 6.1, 5.6, 4.8, 2.3, and 0.1%, respectively. Co-infections were observed at the prevalence rates of 13.4 and 0.5% for double infections and triple infections, respectively. Mixed viral infections were found commonly in Japanese outpatients, and the norovirus seemed to play a major role in co-infections. Viral diarrhea cases were detected mostly in children younger than 3 years of age. The norovirus and rotavirus can be detected throughout the year, with a peak during the cold and dry seasons, whereas other common viruses are found during no specific season. Surveillance data revealed that a wide variety of viruses has caused diarrhea to circulate currently in Japanese pediatric outpatients, with very high detection rates; and norovirus and rotavirus are the most important pathogens. The data obtained from this study are valuable for compiling the overall picture of several viruses that causes diarrhea and associates with acute gastroenteritis in the Japanese pediatric population.

Failure of propagation of human norovirus in intestinal epithelial cells with microvilli grown in three-dimensional cultures.

Human noroviruses (HuNoVs) are a leading cause of acute gastroenteritis. Establishment of a cell culture system for in vitro HuNoV growth remains challenging. Replication of HuNoVs in human intestinal cell lines (INT-407 and Caco-2) that differentiate to produce microvilli in rotation wall vessel (RWV) three-dimensional cultures has been reported (Straub et al. in Emerg Infect Dis 13:396-403, 2007; J Water Health 9:225-240, 2011, and Water Sci Technol 67:863-868, 2013). We used a similar RWV system, intestinal cell lines, and the same (Genogroup [G] I.1) plus additional (GII.4 and GII.12) HuNoV strains to test the system's reproducibility and to expand the earlier findings. Apical microvilli were observed on the surface of both cell lines by light and electron microscopy. However, none of the cell types tested resulted in productive viral replication of any of the HuNoV strains, as confirmed by plateau or declining viral RNA titers in the supernatants and cell lysates of HuNoV-infected cells, determined by real-time reverse transcription PCR. These trends were the same when culture supplements were added that have been reported to be effective for replication of other fastidious enteric viruses in vitro. Additionally, by confocal microscopy and orthoslice analysis, viral capsid proteins were mainly observed above the actin filament signals, which suggested that the majority of viral antigens were on the cell surface. We conclude that even intestinal cells displaying microvilli were not sufficient to support HuNoV replication under the conditions tested.

Clinical features and prognoses of 23 patients with chronic granulomatous disease followed for 21 years by a single hospital in Japan.

In this paper, we examined the details of severe infections, treatment efficacies, and the prognoses of 23 Japanese patients with chronic granulomatous disease (CGD). We described the mean ages at diagnosis and follow-up, which were 2.8 years (range, 0.7-10 years) and 14.9 years (range, 0.2-28.4 years), respectively. There were three deaths, two from Aspergillus pneumonia and one from liver abscess. Eighteen of the 23 patients (78%) had a complete loss of gp91phox, and three had p22-phox and one had p67phox deficiencies. Aspergillus species were found in 45% of 174 severe infections. The mean height and weight of the 20 surviving patients were -0.8 +/- 1.3SD and -1.9 +/- 1.9SD below the means for age, respectively. Short stature and underweight (below the 10th percentile of the means) for age were seen in 22% and 17% of the patients, respectively. This growth retardation reflects the severity of the disease. At 20 years of age, there was 87% survival. Ongoing prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX) or antifungal drugs was given in 16 and 11 patients, respectively. Interferon-gamma (IFN-gamma) was given once a week to 14 patients. Four patients underwent hematopoietic stem cell transplantation (HSCT) and are currently well. There were infections observed in three of 21 identified related carriers of X-linked CGD. A carrier with a liver abscess had 5% normal neutrophils during the acute phase of infection, which returned to 40% normal neutrophils after recovery. The high survival rate in this hospital results from regular follow-up and prophylaxis with TMP-SMX and anti-fungal drugs beginning at the time of diagnosis, along with treatment with weekly IFN-gamma.