Prolonged viral shedding of SARS-CoV-2 in an immunocompromised patient.

The duration of viral shedding of SARS-CoV-2 is usually less than 10 days. We experienced a COVID-19 case with prolonged viral shedding for 2 months. His cell mediated immunity has been depressed (CD4+T cell <100/µl) due to advanced malignant lymphoma and chemotherapy which had been completed 4 months prior to the onset of symptoms of COVID-19. We administered several treatments against COVID-19, however the results of Polymerase Chain Reaction (PCR) from nasopharyngeal specimens remained positive to SARS-CoV-2 for 2 months. Moreover, virus isolation assays performed on Day 59 also remained positive. He was finally discharged on Day 69 with two consecutive negative PCR results for SARS-CoV-2. Immunocompromised status may prolong viral shedding and it is therefore important for the clinician to take into account this when assessing such patients.

Comparing catch-up vaccination programs based on analysis of 2012-13 rubella outbreak in Kawasaki City, Japan.

During the 2012-13 rubella outbreak in Japan, local governments implemented subsidy programs for catch-up vaccination to mitigate the rubella outbreak and prevent congenital rubella syndrome (CRS). In most local governments, to prevent CRS, eligible persons of the subsidy program were women who were planning to have a child and men who were partners of pregnant women. On the other hand, in Kawasaki City, unimmunized men aged 23-39 years were additionally included in the eligible persons, because they were included in an unimmunized men group resulting from the historical transition of the national routine vaccination in Japan. The number of rubella cases in the city decreased earlier than that in the whole Japan. First, in order to estimate the effect of the catch-up vaccination campaign in Kawasaki City on the epidemic outcome, we performed numerical simulations with a Susceptible-Vaccinated-Exposed-Infectious-Recovered (SVEIR) model incorporating real data. The result indicated that the catch-up vaccination campaign showed a beneficial impact on the early decay of the rubella cases. Second, we numerically compared several different implementation strategies of catch-up vaccinations under a fixed amount of total vaccinations. As a result, we found that early and intensive vaccinations are vital for significant reduction in the number of rubella cases and CRS occurrences. Our study suggests that mathematical models with epidemiological and social data can contribute to identifying the most effective vaccination strategy.

Association Between Seasonal Influenza and Absolute Humidity: Time-Series Analysis with Daily Surveillance Data in Japan.

Seasonal influenza epidemics are associated with various meteorological factors. Recently absolute humidity (AH) has garnered attention, and some epidemiological studies show an association between AH and human influenza infection. However, they mainly analyzed weekly surveillance data, and daily data remains largely unexplored despite its potential benefits. In this study, we analyze daily influenza surveillance data using a distributed lag non-linear model to examine the association of AH with the number of influenza cases and the magnitude of the association. Additionally, we investigate how adjustment for seasonality and autocorrelation in the model affect results. All models used in the study showed a significant increase in the number of influenza cases as AH decreased, although the magnitude of the association differed substantially by model. Furthermore, we found that relative risk reached a peak at lag 10-14 with extremely low AH. To verify these findings, further analysis should be conducted using data from other locations.

Septic Meningitis and Liver Abscess due to Hypermucoviscous Klebsiella pneumoniae Complicated with Chronic Strongyloidiasis in a Human T-lymphotropic Virus 1 Carrier.

Recently, severe cases of infection due to hypermucoviscous Klebsiella pneumonia (hmKP) have been reported in Japan. The Amami Islands in Japan are also endemic regions for Strongyloides stercoralis. Disseminated strongyloidiasis strain often causes severe enterobacteria infection; however, whether or not chronic strongyloidiasis induces it remains unclear. We herein report a 71-year-old man who developed meningitis and liver abscess due to hmKP complicated with chronic strongyloidiasis. He died on the seventh hospital day. Strongyloides stercoralis were only found around the polyp in the cecum. Chronic strongyloidiasis can also induce severe infection due to enterobacteria, especially hypervirulent pathogens like hmKP, through the induction of mucosal rupture.

[Evaluation of real-time surveillance of influenza incidence in Kawasaki City by comparison using the National Epidemiological Surveillance of Infectious Diseases].

Objectives　In Japan, nationwide data of the incidence of infectious diseases have been collected via the National Epidemiological Surveillance of Infectious Diseases (NESID) since 1981. In addition, since March 2014, Kawasaki City has operated its own real-time surveillance (RTS) system to collect data of the incidence of influenza from medical institutions across the city. This study aimed to describe the characteristics of the RTS system and compare the two surveillance systems to improve measures against infectious diseases in the future.Methods　NESID and RTS data from March 2014 to October 2017 were obtained from the Kawasaki City Institute for Public Health. First, the operating methodologies of the two surveillance systems were compared. Second, RTS data were used to analyze the daily epidemic curve, and then the daily number of influenza cases was converted into weekly data for comparison with NESID data. Pearson's correlation coefficients and 95% confidence intervals (CIs) were calculated. Correlations were also analyzed after data for the last and first weeks of each year were excluded because few hospitals remain open around the New Year holiday, resulting in a disproportionately large number of patients visiting the few institutions that remain open.Results　The NESID relies on data provided by a fixed number of medical institutions determined each fiscal year (mean: 56.0±4.2 institutions), while the number of institutions providing data for the RTS varies daily or monthly. In September 2017, 691 of the 1,032 eligible institutions (67.0%) were registered for the RTS. Pearson's correlation coefficient for the two surveillance systems was 0.975 (95%CI, 0.967-0.981); when data for the last and first week of each year were excluded, it was 0.989 (95%CI 0.986-0.992). In each of the three seasons that were investigated, an increase in the incidence of type A influenza preceded an increase in the incidence of type B influenza.Conclusion　The operating methodologies of the two surveillance systems differed; however, the results identified a strong correlation, confirming the reliability of the RTS. The RTS collects daily data by influenza type; therefore, it detects epidemic onsets at an earlier stage, facilitating more detailed epidemiological analysis, compared with that of the NESID. It is necessary to understand differences in the characteristics between two surveillance systems when we analyze influenza surveillance data.

Phenotypic and Molecular Characterization of Enteroaggregative Escherichia coli Isolated in Kawasaki, Japan.

Enteroaggregative Escherichia coli (EAEC), an enteric pathogen, causes persistent diarrhea in children, HIV-infected individuals, and travelers in economically developing countries. However, the pathogenesis of EAEC infection is not well understood. This study aimed to characterize EAEC in Japan. Between 2012 and 2014, we identified 40 EAEC strains carrying the aggR gene at the Kawasaki City Institute for Public Health, Japan. We characterized these strains using O:H-antigen typing, polymerase chain reaction (for pCVD432, astA, extended-spectrum beta-lactamase, and 4 aggregative adherence fimbriae genes), HEp-2 cell adherence, clump formation, and antimicrobial susceptibility testing. We were able to classify the 40 EAEC strains into 20 O:H types. Although specific O:H types were not correlated with HEp-2 cell aggregative adherence, all the O99:H10, O131:H27, and O176:H34 EAEC strains that were the most frequent O:H types detected in this study showed co-resistance to ampicillin, sulfamethoxazole-trimethoprim, and tetracycline. Based on results of the adhesion assay and detection of virulence-related genes, no significant difference was found between asymptomatic and symptomatic cases. Irrespective of the origin, their potential for virulence was retained. Further characterization is vital to determine whether EAEC is virulent in Japan.

Molecular evolution of the fusion protein (F) gene in human respiratory syncytial virus subgroup B.

In this study, we examined the molecular evolution of the fusion protein (F) gene in human respiratory syncytial virus subgroup B (HRSV-B). First, we performed time-scale evolution analyses using the Bayesian Markov chain Monte Carlo (MCMC) method. Next, we performed genetic distance, linear B-cell epitope prediction, N-glycosylation, positive/negative selection site, and Bayesian skyline plot analyses. We also constructed a structural model of the F protein and mapped the amino acid substitutions and the predicted B-cell epitopes. The MCMC-constructed phylogenetic tree indicated that the HRSV F gene diverged from the bovine respiratory syncytial virus gene approximately 580years ago and had a relatively low evolutionary rate (7.14×10-4substitutions/site/year). Furthermore, a common ancestor of HRSV-A and -B diverged approximately 290years ago, while HRSV-B diverged into three clusters for approximately 60years. The genetic similarity of the present strains was very high. Although a maximum of 11 amino acid substitutions were observed in the structural model of the F protein, only one strain possessed an amino acid substitution located within the palivizumab epitope. Four epitopes were predicted, although these did not correspond to the neutralization sites of the F protein including the palivizumab epitope. In addition, five N-glycosylation sites of the present HRSV-B strains were inferred. No positive selection sites were identified; however, many sites were found to be under negative selection. The effective population size of the gene has remained almost constant. On the basis of these results, it can be concluded that the HRSV-B F gene is highly conserved, as is the F protein of HRSV-A. Moreover, our prediction of B-cell epitopes does not show that the palivizumab reaction site may be recognized as an epitope during naturally occurring infections.

Longitudinal study on respiratory viral co-infections in the presence or absence of clinical manifestation in infants aged 0-2 years.

We conducted a long-term follow-up study between December 2005 and February 2007 on 4 immunocompetent infants, who repeatedly presented with respiratory symptoms, using PCR-based techniques targeting 14 viruses related to acute respiratory tract infection. Of 38 specimens, 30 were collected from symptomatic infants and 8 were collected when respiratory symptoms were absent. Overall, one or more respiratory viruses were detected in 94.7% (36/38) of the specimens. Of the 36 PCR-positive specimens, 77.8% (28/36) were positive for more than one virus. Most of these co-infections were double infections (55.6% or 20/36). Of note, co-infections with 4 and 3 viruses were observed in 3 (8.3% or 3/36) and 5 (13.9% or 5/36) specimens, respectively. Of the 8 specimens collected from the 4 infants when apparent respiratory symptoms were absent, 7 (87.5%) were positive for respiratory viruses. Respiratory viral co-infections were also frequent and found in 5 of the specimens (62.5%). However, apparent correlation between disease severity and co-infection was undetectable due to the limit of the number of cases studied. Taken together, this longitudinal study revealed that respiratory viral co-infections were not infrequent in infants aged 0-2 years, regardless of the presence of respiratory symptoms (62.5-77.8%).

Clinical and radiologic features of encephalopathy during 2011 E coli O111 outbreak in Japan.

OBJECTIVE: To elucidate the clinical and radiologic features and analyze factors associated with neurologic outcomes of encephalopathy secondary to Shiga toxin-producing Escherichia coli (STEC) O111. METHODS: We reviewed medical records and neuroimaging in 22 patients with neurologic symptoms among 86 with STEC O111 infection. RESULTS: Twenty-one (6 males and 15 females, 10 children and 11 adults) of the 22 patients were diagnosed with encephalopathy. All patients with encephalopathy also presented with hemolytic-uremic syndrome. Five patients died, from day 1 to 6 months (days 1-5 in 4 patients), due to progressive encephalopathy with severe cerebral edema observed in neuroimaging (4 patients). Fifteen of the 16 surviving patients clinically recovered completely. Statistical analysis revealed differences between patients with poor (n = 6) and good (n = 15) outcomes in the interval from hemolytic-uremic syndrome presentation to encephalopathy, creatinine levels, and the methylprednisolone administration ratio. CONCLUSION: We note a high incidence of encephalopathy in the Toyama STEC O111 outbreak. All fatal cases resulted from progressive encephalopathy. Methylprednisolone pulse therapy represents a possible therapeutic choice. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that methylprednisolone pulse therapy increases the probability of a good outcome for patients with encephalopathy associated with STEC O111.

[A case of X-linked alpha-thalassemia/mental retardation (ATR-X) syndrome with repeated apnea attacks due to laryngomalacia].

We report a case of X-linked alpha-thalassemia/mental retardation syndrome (ATR-X) with repeated apnea attacks dating from the patient's 12th year. We initially diagnosed them as obstructive apnea due to upper pharyngeal stenosis and laryngomalacia by polysomnography and laryngo-fiberscopy. However, reevaluation after one and a half years revealed that the boy had central and mixed apnea, as well as obstructive apnea. To date, few reports have been published on the causes of apnea attacks in ATR-X patients. We clinicians should therefore consider laryngomalacia as one cause of apnea attacks in ATR-X patients, and choose the appropriate therapy for a pattern of apnea that can change during its clinical course.