This study aimed to assess the association between the serum glycobiomarker Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA⁺-M2BP) for liver fibrosis and outcomes and carcinogenesis of hepatocellular carcinoma (HCC) in chronic hepatitis C (CHC) patients with advanced fibrosis. Serum WFA⁺-M2BP levels were measured in 128 consecutive CHC patients including 49 with HCC histopathologically diagnosed with advanced fibrosis (44 with fibrosis stage F3 and 84 with fibrosis stage F4) in our hospital. The median WFA⁺-M2BP level was significantly higher in F4 than in F3 patients (6.9 vs. 2.3 cutoff index [COI], respectively; p<0.001). The difference in WFA⁺-M2BP levels between patients with and without HCC was not significant. The respective 5-/8-yr survival rates of patients without HCC at enrollment with high (≥4 COI, n=39), intermediate (1–4 COI, n=33), and low WFA⁺-M2BP (<1 COI, n=7) levels were 78%/48%, 100%/82%, and 100%/100%, respectively. The differences in survival rates between groups were significant (p=0.0041). Patients with high WFA⁺-M2BP levels had a significantly higher incidence of HCC than those with low WFA⁺-M2BP levels (p=0.0019). Cumulative 5-yr carcinogenesis rates in patients with high, intermediate, and low WFA⁺-M2BP levels were 48.7%, 16.9%, and 0%, respectively; the differences between groups were significant (p=0.002). Serum WFA⁺-M2BP levels might allow the prediction of carcinogenesis and outcome in CHC patients with advanced fibrosis.

The influenza season is defined as the period from week 36 of the year to week 20 of the subsequent year in this report. The population size of prefectures (x) and number of patients per prefecture (y) were initially uncorrelated, but a correlation developed as the season advanced. The correlation with correlation coefficient >0.7 emerged increasingly earlier over time; it developed in week 5 of the subsequent year in 2001/2002, but in week 47 of the same year in 2014/2015. Once x and y were correlated, plots of y on the vertical axis against x on the horizontal axis resulted in a straight line, y = Cx^s, where s was the slope of the plot and C was a constant. The slope was high (s>1) initially, but decreased (s<1) later, indicating that influenza first spread to populated prefectures and then nationwide, involving less populated prefectures. This spread pattern was the same for the seasonal influenza and AH1pdm2009, although the progression of the latter was much faster. For measles and rubella epidemics, the number of patients per prefecture was proportional to the square of the population size from the start to the end of the season.

Community-acquired brain abscesses are still encountered in clinical practice and cause considerable complications, despite improvements in hygiene in modernized societies. This study aimed to identify potential risk factors pertaining to predisposing infections and microorganisms to facilitate the effective treatment of brain abscesses. Of 121 surgically treated patients with brain abscesses, the most frequent predisposing condition was odontogenic infections (49/121 patients, 40.5%) followed by sinusitis (14/121, 11.6%). Of 121 patients, 51 (42.1%) had no identifiable predisposing infection. Viridans group streptococci (VGS) were the most frequently identified (47%) bacteria in all patients, and anaerobes were more frequently isolated in patients with odontogenic infections (36.7%, p=0.001) than aerobes. Among the patients with no identifiable predisposing infection, the most commonly isolated pathogen was VGS (38.3%); anaerobes occurred significantly less frequently (p=0.045), and old pulmonary tuberculosis was significantly more common (p=0.001) than in the group with identified predisposing infections. There was only one case of staphylococcal infection in 121 patients. The present study indicates that VGS should be the first target for antibiotic treatment when predisposing infections are not identifiable in patients with brain abscesses. Additionally, the association of old tuberculosis with community-acquired brain abscesses is common in these patients.

Brucella infection is accompanied by cytokine production, which serves as an important factor to evaluate the innate and adaptive immune responses. Several researchers have been investigating the mechanisms involved in Brucella infection in the host. Here, we conducted an analytical study to define pathogenic pathways and immune mechanisms involved in Brucella infection by investigating the antigenic efficacy of recombinant outer membrane protein 10 (rOMP10), outer membrane protein 19 (rOMP19), and outer membrane protein 28 (rOMP28) in vitro and in vivo upon stimulation/immunization. Cytokine production was analyzed by nitric oxide (NO) assay and enzyme-linked immunosorbent assay (ELISA) after stimulation of RAW 264.7 cells and naive splenocytes with the recombinant proteins. Our results show that levels of NO, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 increased in RAW 264.7 cells in a time-dependent manner following recombinant protein stimulation. In contrast, levels of interferon (IFN)-γ and IL-2 increased in naive splenocytes after stimulation with proteins. ELISA and ELISpot assays were performed after immunization of mice with recombinant proteins. rOMP28 greatly increased IFN-γ, IL-2, and TNF-α levels than IL-4 and IL-6 levels in vitro. Of the recombinant proteins, rOMP19 elicited a mixed Th1/Th2 immune response by increasing the number of IgG-secreting cells in vivo.

Crimean-Congo hemorrhagic fever virus is a risk group 4 pathogen, which mandates the use of maximum containment facilities, often termed biosafety level 4 or containment level 4 when working with infectious materials. Diagnostic and research work involving live viruses in such laboratories is time-consuming and inconvenient, resulting in delays. Herein, we show that serum neutralizing activity against the virus can be measured in low-containment laboratories using a pseudotyped virus.

Three relapse cases were reported out of 107 hospital-attending typhoid cases within a period of 2 years (2014–2016) from Apollo Gleneagles Hospital, Kolkata, India. During the first episode of typhoid fever, 2 of the 3 cases were treated with ceftriaxone (CRO) for 7 days, and 1 was treated for 14 days. Six Salmonella Typhi (S. Typhi) isolates, obtained from the 3 patients during both typhoid episodes, were subjected to antimicrobial susceptibility testing, detection of quinolone resistance-determining region (QRDR) mutation and molecular subtyping by pulsed-field gel electrophoresis (PFGE), multiple-locus variable number tandem repeat analysis (MLVA), multilocus sequence typing (MLST), clustered regularly interspaced short palindromic repeats (CRISPR), and H58 haplotyping. Pairs of the S. Typhi strains isolated from two of the patients during the 1st and 2nd episodes were similar with respect to the antimicrobial resistance (AMR) profiles, QRDR mutations, and molecular subtypes; whereas, the S. Typhi strain pair isolated from the 3rd patient were different in their AMR profiles, QRDR mutations, and MLVA profiles. From these observations, it may be concluded that in spite of treating typhoid cases with CRO for 7–14 days, relapse of typhoid fever might occur. The article also showed the advantage of MLVA typing over PFGE, MLST, and CRISPR typing for the discrimination of strains isolated from the same patient in case of relapse of typhoid fever.

Tuberculosis (TB) among healthcare workers (HCWs) highly affects morbidity and TB transmission in hospitals. A retrospective cohort study of TB among HCWs (HCW-TB) was conducted using a registered database from 2003 to 2016 at Chiang Mai University Hospital to determine clinical and microbiological characteristics and treatment outcomes of HCW-TB. A total of 76 patients comprising 54 nurses (71.1%), 12 physicians (15.8%), and 10 paramedics (13.2%) were diagnosed with TB disease. The men to women ratio was 25:51, with a mean age of 37.0±11.6 years, a median work duration of 12.0 years (5–20) and a body mass index of 19.4±2.5 kg/m². Within the HCW-TB group, 28 (36.8%) worked in the Medical Department, 12 (15.8%) worked in the Outpatient Department/Emergency Room, and 9 (11.8%) worked in the Surgical Department. Pulmonary TB (PTB) was the most common manifestation of HCW-TB (92.1%). Sputum acid-fast stains were positive among 28 (40.0%) HCWs with PTB. Mycobacterium tuberculosis cultures were positive in 26 (34.2%) patients. Drug susceptibility testing showed sensitivity to all first-line drugs (75.0%), resistance to any one first-line drug (20.8%), and multidrug-resistant TB comprised 4.2%. The end-of-treatment success rate was 100%. Therefore, TB control guidelines should be strictly implemented to prevent TB transmission in healthcare settings.

Long-term complications of protease inhibitor (PI) treatment includes increased cardiovascular risks due to dyslipidemia in patients infected with human immunodeficiency virus (HIV). Ezetimibe reduces low-density lipoprotein cholesterol (LDL-C) without drug interactions with PIs and statins. Furthermore, the addition of ezetimibe to statins is an optional treatment in HIV-infected patients with uncontrolled dyslipidemia. The objective of this study was to determine the short-term efficacy and safety of adding ezetimibe to the currently administered statin regimen. Thirty-two patients received ezetimibe (10 mg daily) in addition to their ongoing lipid-lowering therapy for 18 weeks. Serum LDL-C, total cholesterol (TC), triglycerides (TGs), TC/high-density lipoprotein cholesterol (HDL-C) ratio, and HDL-C were measured at baseline, and weeks 6, 12, and 18. Safety parameters were assessed by adverse event reports and laboratory assessments throughout the study. The mean percent change from baseline to endpoint in LDL-C, TC, TGs, and TC/HDL-C ratio were −23.3% (p<0.001), −15.0% (p=0.001), −22.1% (p=0.004), and −16.2% (p=0.018), respectively. No adverse event or other abnormal laboratory results occurred. Addition of ezetimibe to currently administered lipid-lowering drugs in HIV-infected patients receiving PIs with uncontrolled dyslipidemia demonstrated significantly improved efficacy in reducing their LDL-C, TC, TGs, and TC/HDL-C ratio levels. Moreover, this therapy was safe and well-tolerated.

Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne infection with a high mortality rate. It is caused by the SFTS virus (SFTSV) and is endemic in some areas in western Japan, including the Kagoshima prefecture. In the present study, healthy individuals living in this prefecture were examined to assess for anti-SFTSV seroprevalence. An initial study was performed using the serum samples collected from a total of 646 individuals living in Kagoshima. At the same time, a questionnaire was used to collect information (such as occupation and a history of tick bite). Enzyme-linked immunosorbent assay and indirect immunofluorescence assay were used for the screening. Finally, the seroprevalence of anti-SFTSV antibodies was confirmed using a neutralization assay. Only 2 (0.3%) out of 646 study participants were positive for anti-SFTSV antibodies. No significant difference was observed between individuals who are at a high or low risk of tick bite in terms of seropositivity. Next, a total of 1,000 serum samples collected from general blood donors by the Japanese Red Cross Kyushu Block Blood Center were tested. None of these samples tested positive for anti-SFTSV antibodies. These results suggest a low seroprevalence of anti-SFTSV antibodies in healthy individuals living in an endemic area in Japan.

A novel system was developed for generating highly attenuated vaccinia virus LC16m8 (m8, third-generation smallpox vaccine) that expresses foreign genes. The innovations in this system are its excisable selection marker, specificity of the integration site of a gene of interest, and easy identification of clones with a fluorescent signal. Using this system, recombinant m8s, which expressed herpes simplex virus 2 (HSV-2) glycoprotein B (gB)-, gD-, or both gB and gD (gB + gD), were generated, and their efficacy was evaluated. First, the induction of a specific IgG against these HSV-2 glycoproteins in mice infected with one of these recombinant m8s was confirmed by an immunofluorescent assay. Next, mice preinfected with one of the recombinant m8s were infected with HSV-2 at a lethal dose to examine the vaccine efficacy. The fatality rate among the mice preinfected with either the recombinant gB + gD- or gD-expressing m8 significantly decreased in comparison with the control. The survival rate in male and female mice preinfected with either the recombinant gB + gD- or gD-expressing m8 increased to 100% and 60%, respectively, while most of the control mice died. In summary, this new system may be applicable to creation of a novel m8-based vaccine.

Antigenic changes in the hemagglutinin protein of recent A(H3N2) viruses often arise when these viruses adapt to their egg host. By serial egg passages of a cell-propagated virus, we successfully isolated an egg-adapted influenza A(H3N2) virus, A/Saitama/103/2014, without amino acid substitutions at the antigenic sites of its hemagglutinin protein but with multiple substitutions in its neuraminidase protein. Antigenic analysis of this egg-adapted A/Saitama/103/2014 virus indicated that its antigenicity did not differ from that of the World Health Organization prototype cell-propagated vaccine virus: A/Hong Kong/4801/2014. Our results suggest that this strategy may facilitate egg-based vaccine production without antigenic alterations in hemagglutinin by egg adaptation.

Severe dengue is more prevalent in adults than in children. Our objectives were to determine the clinical presentations of dengue in adults and to identify predictive factors for severe dengue. A retrospective cohort study was performed in adults with dengue, as confirmed by a positive NS1 antigen test result. Patients were classified as with non-severe or severe dengue. A total of 357 patients were enrolled; 45.4% were men, with a median (interquartile range [IQR]) age of 27.9 (21.8–43.5) years. Of all patients, 28.3% had warning signs and 10.6% had severe dengue. Patients with severe dengue were significantly older (35.1 [26.2–50.6] vs. 26.7 [21.7–43.3] years, P = 0.010), immunocompromised (7.9% vs. 0.9%, P = 0.018), and had cough (29% vs. 16%, P = 0.046), hepatomegaly (10.5% vs. 3.1%, P = 0.050), impaired consciousness (5.3% vs. 0%, P = 0.011) or higher (IQR) alanine aminotransferase (ALT) level (151 [57–295] vs. 66 [37–114] U/L, P = 0.008). By multivariate analysis, having cough (odds ratio [OR], 8.07; 95% confidence interval [CI], 2.51–30.16, P = 0.001) and ALT>120 U/L (OR, 3.51; 95% CI, 1.11–11.14, P = 0.033) were predictors of severe dengue. Early recognition of risk variables may be important for healthcare providers to appropriately manage dengue patients.

Although invasive meningococcal disease is rare in Japan (0.028 cases per 100,000 population), its incidence is 10 times greater in many other countries. Colonization is a prerequisite for invasive meningococcal disease. However, no study in Japan has involved specifically analyzing the carriage rate of Neisseria meningitidis in children. During 5 months in 2015, the respiratory tract specimens of patients who presented to 3 hospitals with respiratory symptoms were cultured. The bacteria were identified in selective media using a meningococcal detection kit and the serogroup was identified using polymerase chain reaction analysis. In 389 patients aged ≤15 years with respiratory symptoms, the N. meningitidis isolation rate was 0.26% (1/389). The serogroup of the only child who tested positive was Y. In this study, we detected a low meningococcal isolation rate in pediatric patients. Due to increasing globalization, the risk of invasive meningococcal disease is likely increasing in Japan. Accordingly, invasive meningococcal diseases should be continuously monitored in Japan. Future large-scale studies should assess meningococcal isolation rates and corresponding serogroups.

The spread and establishment of Chandipura virus (CHPV) infection in India has raised serious epidemiological concerns. The virus interface with the vertebrate hosts (including humans) and vector competence are the important parameters of disease prevalence. Interestingly, in the present study, a highly zoophilic species of the sandfly Sergentomyia was found to be a potential vector of CHPV in Gujarat. This is probably the first report from India of male sandflies testing positive for CHPV in RT-PCR analysis. These findings signify vertical transmission of the virus among sandflies and have epidemiological significance. Health Officers from Gujarat referred 9 pools comprising 277 adult sandflies from disease-affected and unaffected areas to the National Institute of Virology, Pune. The pools were subjected to RT-PCR analysis and sequencing. Of the 9, 2 female and one male pool tested positive for CHPV. Phylogenetic analysis showed similarity of the new sandfly-borne CHPV strains with the human strain from Andhra Pradesh (AP) 2003. The present study highlights the possible role of Sergentomyia spp. in the transmission of CHPV in India.

Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract illness in infants and young children. In Japan, surveillance for RSV infection started in 2003 based on approximately 3,000 pediatric sentinel sites. In recent years, RSV notifications have increased, but the interpretation of trends has been challenging due to a suspected increase in testing frequency and the expansion of the insurance coverage for RSV testing to include certain outpatients in late 2011. Therefore, we evaluated RSV surveillance data during 2008–2015, considering the number of sites that reported at least one RSV case during a surveillance year and restricting to sites that had continuous reporting status since 2008. While annual RSV notifications had increased, the number of sites reporting also increased. And the same magnitude of increase was not observed when the number of cases reported was restricted to the 1,372 sites that had continuous reporting status since 2008. Additionally, in the year following the insurance expansion, RSV notifications increased more remarkably for clinics than for hospitals. These results suggested that some of the recent increases in notifications might be due to an increase in testing frequency.