The World Health Organization Western Pacific Region (WPR) has maintained a polio-free status for more than two decades. At the global level, there were only six confirmed polio cases due to wild type 1 poliovirus in Pakistan, Afghanistan, and Malawi in 2021; therefore, the risk of wild poliovirus importation from endemic countries to the WPR is considerably lower than that in the past. However, the risk of polio outbreaks associated with circulating vaccine-derived polioviruses (cVDPVs) cannot be ignored even in the WPR. Since the late 2010s, cVDPV outbreaks in the WPR have increased in frequency and magnitude. Moreover, the emergence of concomitant polio outbreaks of type 1 and type 2 cVDPVs in the Philippines and Malaysia during 2019–2020 highlighted the potential risk of cVDPV outbreaks in high-risk areas and/or communities in the WPR. Previous cVDPV outbreaks in the WPR have been rapidly and effectively controlled. However, future polio outbreak risks associated with cVDPVs must be reconsidered, and polio immunization and surveillance strategies should be updated accordingly.

To maintain the performance quality, human immunodeficiency virus (HIV) in vitro diagnostic (IVD) kits are required to be evaluated by unbiased health regulatory organizations following predefined guidelines. The World Health Organization (WHO) prequalification is one such program for the evaluation of IVD assays. In the present systematic review and meta-analysis, we analyzed and compared the 17 WHO prequalified public reports of HIV IVDs to yield summarized information for performance parameters. Pooled sensitivity, pooled specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were used as overall performance evaluation parameters. High (≥98%) and comparable levels of sensitivity and specificity were observed for most of the assays. In addition, the overall diagnostic efficiency was observed to attain high precision, as evident by the value of the area under the curve (AUC) for the hierarchical summary receiver operating characteristic curve (AUC ≥ 0.98).

Novel immunodominant antigens are urgently required for the diagnosis and vaccination of Helicobacter pylori (HP). FliD, an important colonization factor, was cloned and expressed (rFliD) to evaluate the levels of specific immunoglobulin G (IgG), IgM, and IgA antibodies in the serum of patients using ELISA. Rabbit anti-rFliD polyclonal antibody (pAb) was obtained by the subcutaneous injection of rFliD. The rFliD-specific IFN-γ and IL-4 levels in peripheral blood mononuclear cells and CD4⁺ T cells from humans were analyzed using enzyme-linked immunospot and flow cytometry. We found that the levels of rFliD-specific IgG, IgM, and IgA were significantly higher in HP-infected-patients than in healthy controls. IgG, IgM, and IgA had diagnostic sensitivities of 92.6%, 89.8%, and 83.2%; specificities of 91.1%, 88.7%, and 64.6%; and areas under the receiver operating curves of 0.97, 0.96, and 0.92, respectively. Furthermore, rFliD-pAb was used for the immunohistochemical analysis of gastritis and gastric cancer tissues from patients infected with HP. The levels of rFliD-specific IFN-γ and IL-4 were significantly elevated in HP-infected patients and exhibited a dominant T helper type 1-dominant subtype. These findings indicate that rFliD exhibits high validity as a biomarker in HP diagnosis and may also be a potent antigen for vaccine design because of its high cellular and humoral immune responses.

Intra-abdominal infections (IAIs) develop in 2.4%–26.6% of patients who underwent gastrectomy for gastric cancer and are occasionally serious. However, there are few reports on the causative organisms of IAI following upper gastrointestinal tract surgery and subsequent risk factors for Candida infections. This study aimed to identify the microorganisms that cause IAIs after gastrectomy and risk factors for Candida-related IAI. The records of patients who underwent gastrectomy for gastric cancer between January 2009 and December 2019 at Shizuoka General Hospital were retrospectively collected. Patients with IAIs of grade II or higher, as measured by the Clavien–Dindo classification, were included in the analysis. The selected patients were divided into the Candida and non-Candida groups according to the presence or absence of Candida as the causative organism. Of 1,379 patients, 56 (4.1%) were diagnosed with IAIs after gastrectomy. Fifty-two patients were included in the study based on culture analyses. A total of 111 strains and 28 bacterial species were isolated during the initial culture test. Candida constituted 7.2% of all identified pathogens. Regarding the risk factors for Candida-related IAI, a history of antimicrobial use and ≥ 4 postoperative days of IAI development were independent risk factors for Candida-related IAI.

The emergence of unusual G9P[8]-E2 human rotaviruses in the Tokyo metropolitan area, Japan, in 2018 has been reported. During rotavirus strain surveillance in different regions of Japan (Mie, Okayama, and Chiba prefectures), G9P[8]-E2 strains were detected in children with diarrhea from all three prefectures. Here, we characterized the whole genome of seven representative G9P[8]-E2 strains. In the full-genome-based analysis, the seven study strains exhibited a unique genotype configuration with the NSP4 gene of genogroup 2 in a genogroup 1 genomic backbone: G9-P[8]-I1-R1-C1-M1-A1-N1-T1-E2-H1. This genotype constellation was shared by the Tokyo G9P[8]-E2 strains. Phylogenetic analysis showed that all 11 genes, except NSP4, of the seven study strains appeared to have originated from co-circulating Wa-like G9P[8]-E1 strains. In contrast, NSP4 appeared to have originated from the co-circulating DS-1-like G2P[4]-E2 strains. Thus, G9P[8]-E2 strains appear to be derived through reassortment between G9P[8]-E1 and G2P[4]-E2 strains in Japan. Notably, the seven study G9P[8]-E2 strains and Tokyo G9P[8]-E2 strains were revealed to have 11-segment genomes almost indistinguishable from one another in their sequences (99.3–100%), indicating all these G9P[8]-E2 strains had a common origin. To our knowledge, this is the first description of the rapid spread of G9P[8]-E2 strains across a country.

Over the past few decades, the clinical features of pulmonary cryptococcosis (PC) have progressed; however, there is a lack of data on the manifestations of PC over time. To investigate the differences in the clinical characteristics of PC across different time periods, we retrospectively reviewed 130 non-acquired immunodeficiency syndrome (AIDS) patients diagnosed with pathologically or microbiologically confirmed PC from 1990–2020. Among the 130 patients with PC, 24 (18.5%) exhibited immunosuppression, and 44 (33.8%) had underlying diseases. In radiology, 118 (90.8%) presented with subpleural lesions, and 68 (53.1%) presented with nodules with diameters ranging from 1–5 cm. Seventy-five (57.7%) patients underwent surgery alone. The clinical features of PC at different time periods showed that hospitalization days decreased (P = 0.009), and the number of patients with symptoms decreased over time. The number of patients exhibiting isolated lesions decreased (P = 0.022), and the number of patients exhibiting subpleural lesions increased (P = 0.020). In addition, the number of patients with lesions presenting 3–10 mm nodules increased (P = 0.028). In conclusion, an increasing number of patients have been diagnosed with PC over the last 30 years. The timing of PC diagnosis has shifted to the early stages of disease progression. Pulmonary lesions caused by cryptococcosis are easily misdiagnosed and may require unnecessary surgical treatment. Further research is needed to identify the lung lesions caused by cryptococcosis.

Coronavirus disease (COVID-19) has spread dramatically worldwide. Nafamostat mesylate inhibits intracellular entry of the novel severe acute respiratory syndrome coronavirus 2 and is believed to have therapeutic potential for treating patients with COVID-19. In this study, patients with moderate COVID-19 who were admitted to our hospital were retrospectively analyzed. Thirty-one patients received monotherapy with nafamostat mesylate, and 33 patients were treated conservatively. Nafamostat mesylate was administered with continuous intravenous infusion for an average of 4.5 days. Compared with the conservative treatment, nafamostat mesylate did not improve outcomes or laboratory data 5 days after admission. In addition, no significant differences in laboratory data 5 days after admission and outcomes in high-risk patients were observed. The incidence of hyperkalemia was significantly higher in the nafamostat mesylate group; however, none of the patients required additional treatment. In conclusion, monotherapy with nafamostat mesylate did not improve clinical outcomes in patients with moderate COVID-19. This study did not examine the therapeutic potential of combining nafamostat mesylate with other antiviral agents, and further investigation is required. Because of the high incidence of hyperkalemia, regular laboratory monitoring is required during the use of nafamostat mesylate.

Candida auris, first described from an ear infection in Japan, is an important emerging multidrug-resistant pathogenic fungal species. Its environmental niche remained a mystery until its isolation from the wetlands of the Andaman Islands, India, in 2020. We screened a subset of the world’s largest sequence repository, the Sequence Read Archive at National Center for Biotechnology Information, using a DNA metabarcoding approach based on either the internal transcribed spacer (ITS)1 or ITS2 region of the official primary fungal DNA barcode, to identify potential environmental sources of C. auris. Our search identified 34 matches with partial C. auris ITS sequences from seven metabarcoding studies, providing wider evidence for the presence of C. auris outside human-maintained facilities.

Neutralizing antibodies (NAbs) to human cytomegalovirus (HCMV) are associated with the risk of transplacental HCMV infection of the fetus in pregnant women. The IgG-positivity rate to HCMV determined by enzyme immunoassay (EIA) or indirect immunofluorescence assay has decreased from approximately 100% to 70% over the past 30 years in Japan. We tested serum samples from 630 Japanese women aged 20–49 years whose blood samples were obtained between 1980 and 2015. IgG titer was measured using an EIA-based assay. HCMV-NAb titer was measured using a neutralization test assay with an HCMV isolate on human retinal epithelial cells. Longitudinal transitions in HCMV-NAb prevalence were clarified. The prevalence of HCMV-EIA-IgG, and HCMV-NAb at a titer of 16-fold, and HCMV-NAb at a titer of 100-fold, changed from 96.7% to 78.9%, 93.3% to 85.6%, and 35.5% to 41.1%, respectively, between 1980–1990 and 2010–2015. Prevalence of HCMV-NAb at a titer of 16-fold decreased by 7.7%, whereas that at a titer of 100-fold increased by 5.6%. A high titer of HCMV-NAb in pregnant women is expected to reduce the risk of intrauterine HCMV transmission from the mother to the fetus. The association between the risk of congenital HCMV infection and the prevalence of HCMV-NAb remains to be addressed.

Factors associated with mortality are important in the treatment of coronavirus disease 2019 (COVID-19). Polymerase chain reaction (PCR) is the gold standard for diagnosing COVID-19, which reflects the viral load in the upper respiratory tract. In total, 523 patients were enrolled in this study; of them, 441 and 75 patients underwent PCR testing of nasopharyngeal swabs and sputum samples, respectively, within 20 days from onset of COVID-19. We investigated the association between RNA copy number and the COVID-19 severity and mortality rate and its effect on the predictive performance for severity and mortality. RNA copy numbers in nasopharyngeal swabs were higher in the non-survivor group than in the survivor group. Multivariate logistic regression analysis identified that the high RNA copy number (≥9 log₁₀ /swab) in nasopharyngeal swabs was a factor associated with mortality (odds ratio, 4.50; 95% confidence interval, 1.510–13.100; P = 0.008). Furthermore, adding RNA copy number (≥9 log₁₀ /swab) in severe cases, adjusted by duration from onset to PCR, improved mortality predictive performance based on known factors. The RNA copy number is a factor associated with the mortality of patients with COVID-19 and can improve the predictive performance of mortality in severe cases.

To estimate the effect of the corona virus disease 2019 (COVID-19) control measures taken to mitigate community transmission in many regions, we analyzed data from the influenza surveillance system in Beijing from week 27 of 2014 to week 26 of 2020. We collected weekly numbers of influenza-like illness (ILI) cases, weekly positive proportion of ILI cases, weekly ILI case proportion in outpatients, and the dates of implementation of COVID-19 measures. We compared the influenza activity indicators of the 2019/2020 season with the preceding five seasons and built two ARIMAX models to estimate the effectiveness of COVID-19 measures declared since January 24, 2020 by the emergency response. Based on the observed data, compared to the preceding five influenza seasons, ILIs, positive proportion of ILIs, and duration of the influenza epidemic period in 2019/2020 had increased from 13% to 54%; in particular, the number of weeks from the peak to the end of the influenza epidemic period had decreased from 12 to 1. According to ARIMAX model forecasting, after considering natural decline, weekly ILIs had decreased by 48.6%, weekly positive proportion had dropped by 15% in the second week after the emergency response was declared, and COVID-19 measures had reduced by 83%. We conclude that the public health emergency response can significantly interrupt the transmission of influenza.

We performed a pilot study to assess the immunogenicity and safety of intradermal hepatitis B (HB) virus vaccines in people living with HIV (PLWH). This single-center prospective study was conducted in Yokohama, Japan. Adult PLWH with serum antibodies against HB surface antigen (anti-HBs) <10 mIU/mL at all time points after standard HB vaccination were included. We administered HB surface antigen (total dose of 10 μg) at 5 separate sites intradermally at baseline, one month, and 6–9 months and measured anti-HBs 1–3 months after administration. Eleven PLWH were included in this study. The mean age was 36 years, and all patients were men. At baseline, all patients were on antiretroviral therapy, and the mean CD4+ lymphocyte count was 588 /μL and plasma HIV-RNA was <20 copies/mL, except for one patient. Anti-HB levels were elevated to >10 mIU/mL in one patient after one dose, 6 patients after 2 doses, and 4 patients after 3 doses of the intradermal vaccines. Eight patients experienced grade 1 local adverse events. Additional vaccination via the intradermal route induced an anti-HBs level >10 mIU/mL in all patients, without serious adverse events.

We conducted two-year seroprevalence surveys of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies among outpatients and healthcare workers (HCWs) at Ehime University Hospital. Data were collected for outpatients and HCWs in June 2020 (1st survey), December 2020 (2nd survey), July 2021 (3rd survey), and December 2021 (4th survey), focusing on demographics, occupation, and the seroprevalence of anti-SARS-CoV-2 antibodies. Blood samples were obtained from randomly selected outpatients who visited our hospital for medical care and HCWs undergoing regular medical checks with opt-out informed consent. SARS-CoV-2 antibody positivity was evaluated using two laboratory-based quantitative tests. The total number of participants enrolled was 6,369 (1st survey: 1,000 outpatients and 743 HCWs, 2nd survey: 1,000 outpatients and 407 HCWs, 3rd survey: 1,000 outpatients and 804 HCWs, 4th survey: 1,000 outpatients and 415 HCWs). The prevalence of SARS-CoV-2 antibodies among outpatients and HCWs was 0–0.1% and 0–0.124% during the research period, respectively, and changed little over time. These findings suggest that the magnitude of COVID-19 infection during the pandemic among outpatients and HCWs in this rural hospital might have been small.

In mid-September 2019, a teenage Chinese male student and part-time waiter in Tokyo was diagnosed with multidrug-resistant (MDR) sputum smear-positive pulmonary tuberculosis (TB). This study describes the outbreak investigation of his friends and colleagues at the restaurant. We investigated 6 friends and 15 colleagues; 5 friends and 13 colleagues underwent interferon-γ release assay (IGRA). Of these, 3 friends (60.0%) and 4 colleagues (30.8%) were IGRA-positive. Each of the friends and colleagues was found to have MDR-TB (20% and 7.7%, respectively). Challenges during the investigation were the unavailability of regimens for latent TB infection (LTBI) for contacts with MDR-TB, budgetary constraints concerning implementing computed tomography (CT) scans for the contacts, frequent address changes of foreign-born patients and contacts, investigation during the coronavirus disease pandemic, and variations of alphabetical expression of the names of the patients and contacts, particularly for those from China. It is recommended that the national government officially adopt prophylaxis regimens for LTBI with MDR-TB, address the budgetary constraints regarding CT scans, and deploy liaison officers for coordinating investigations involving many foreign-born patients and contacts scattered in multiple municipalities. The names of foreign-born persons could more accurately be identified using both the alphabet and Chinese characters.

Respiratory infections are common, and the most common causative agent is a virus. Therefore, routine surveillance of respiratory viruses is useful in the case of novel viral diseases such as coronavirus disease 2019 (COVID-19). In this study, to clarify the kind of virus involved in suspected cases of COVID-19 in the early stages of the pandemic, we attempted to detect various respiratory viruses in 613 specimens that tested negative for severe acute respiratory syndrome coronavirus 2 using reverse transcription polymerase chain reaction. As a result, viruses were detected in 59 (9.6%) patients. In addition, human rhinovirus (HRV), human metapneumovirus (HMPV), human respiratory syncytial virus, and human parechovirus were detected in 29, 25, 3, and 2 patients, respectively. Although this study was conducted over a short period of time and not all specimens were tested, these results indicate that various respiratory viruses, especially HRV and HMPV, can be detected even during the early stages of the COVID-19 pandemic. Because various respiratory viruses maintain a constant effect during the outbreak of the newly emerged pandemic, systematic surveillance of respiratory viruses is needed during the normal period to make good use for clinical and public health.

Hantavirus hemorrhagic fever with renal syndrome (HFRS) is an emerging zoonotic disease in Europe and Asia, which is clinically indistinguishable from leptospirosis. A total of 1,032 patients with clinical suspicion of HFRS-like illness were included in the analysis from March 2013 to March 2021. Of these, 168 were positive for hantavirus immunoglobulin M (IgM) antibodies. Thirty-one of 35 patients had a 4-fold increase in IgG antibody titer with paired serum, confirming acute hantavirus infections. The detected antibodies showed a diverse pattern, strongly cross-reacting with the Seoul, Hantaan, and Puumala virus antigens. All the IgM-positive patients had no serological evidence of acute dengue or leptospirosis and had classical features of HFRS, including fever, thrombocytopenia, and renal involvement. More than 90% of patients had a history of rodent exposure 2–3 weeks prior to the onset of the fever. The highest number of positive cases was diagnosed in the Western and North Central Provinces of Sri Lanka during the paddy harvesting seasons. A significant number of patients develop severe complications with high mortality rates. Therefore, hantavirus infection should be considered as a differential diagnosis for leptospirosis-like illnesses in Sri Lanka.