Coronavirus disease 2019 (COVID-19) expanded dramatically all over the world. Nafamostat mesylate inhibits the intracellular entry of novel severe acute respiratory syndrome coronavirus 2 and it has been thought as the therapeutic potential of treatment for patients with COVID-19. In the present study, patients with moderate COVID-19 who were admitted to our hospital were retrospectively analyzed. 31 patients received nafamostat mesylate monotherapy and 33 patients received conservative treatment. Nafamostat mesylate was initiated by continuous intravenous infusion for 4.5 days on average. Comparing with conservative treatment group, nafamostat mesylate did not improve the outcomes and laboratory data 5 days after admission. There were also no significant differences in the laboratory data 5 days after admission and outcomes in high-risk patients. Incidence of hyperkalemia was significantly higher in the nafamostat mesylate group, however, none of the patients required additional treatment for hyperkalemia. In conclusion, nafamostat mesylate monotherapy did not improve clinical outcomes in patients with moderate COVID-19. The therapeutic potential of the combination of nafamostat mesylate and other antiviral agents has not been examined in the present study, and further investigation is required. Because of high incidence of hyperkalemia, regular laboratory tests are required during the use of nafamostat mesylate.
The neutralizing antibodies (NAb) to HCMV in women are associated with the risk of transplacental infection of the fetus with HCMV in pregnant women. The IgG-positive rate determined with enzyme immunoassay (EIA) or indirect immunofluorescence assay has decreased approximately from 100% to 70% over the past 30 years in Japan. We tested serum samples from 630 women in Japan aged 20 to 49 years from whom blood had been drawn between 1980 and 2015. We measured the IgG titer using an EIA-based assay and the HCMV-NAb titer with neutralization test assay using an HCMV isolate on human retinal epithelial cells. Longitudinal transitions of HCMV-NAb prevalence were clarified. The prevalence of HCMV-EIA-IgG, HCMV-NAb of 16 titer, and HCMV-NAb of 100 titer changed from 96.6 to 78.9%, 93.3% to 85.6%, and 35.5% to 41.1%, respectively, between 1980-1990 and 2010-2015. HCMV NAb prevalence at the titer of 16 decreased by 7.7%, whereas that at the NAb titer of 100 increased by 4.6%. It is expected that HCMV NAb with high titer in pregnant women reduces the risk of intrauterine HCMV transmission from mother to fetus. The association between the risk of congenital HCMV infection and HCMV-NAb prevalence remains to be addressed.
We performed this pilot study to assess the immunogenicity and safety of intradermal hepatitis B (HB) virus vaccines in people living with HIV (PLWH). A single-center prospective study was conducted in Yokohama, Japan. Adult PLWH with serum antibodies against hepatitis B surface antigen (anti-HBs) < 10 mIU/mL at all the points after standard HB vaccination were included. We administered hepatitis B surface antigen (total dose 10 μg) at five separate sites intradermally at baseline, 1 month, and 6-9 months and measured anti-HBs 1-3 months after the administration. A total of 11 PLWH were included in this study. The mean age was 36 years, and all patients were male. At baseline, all patients were on anti-retroviral therapy, and the mean CD4 + lymphocyte count was 588 /μL and plasma HIV-RNA was below 20 copies/mL, except for one participant. Anti-HBs levels were elevated over 10 mIU/mL in one participant after one dose, six participants after two doses, and four participants after three doses of the intradermal vaccines. Eight participants experienced grade 1 local adverse event. Additional vaccination via intradermal route induced an anti-HBs level > 10 mIU/mL in all participants without serious adverse events.
Hantavirus; Hemorrhagic fever with renal syndrome (HFRS) is an emerging zoonotic disease in Euro-Asia which is clinically indistinguishable from leptospirosis. A total number of 1032 patients were included in the analysis from March 2013 to March 2021 with the clinical suspicion of HFRS-like illness. Of them, 168 patients were positive for hantavirus IgM antibodies. Thirty-one patients out of 35 patients had given a four-fold rise IgG antibody titre with paired serum confirming the acute hantavirus infections. Detected antibodies showed a diverse pattern, strongly cross-reacting with 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; 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 were diagnosed from the Western and North-Central Provinces of Sri Lanka during the paddy harvesting seasons. A significant number of patients had developed severe complications with a high mortality rate. Therefore, hantavirus infection should be considered as a differential diagnosis for leptospirosis-like illness in Sri Lanka.
Intra-abdominal infections (IAIs) occur in 2.4%–26.6% of patients who undergo 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 the subsequent risk factors for Candida infection. This study aimed to identify the microorganisms causing IAIs after gastrectomy and the 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 2 or higher as measured by the Clavien–Dindo classification were included in the analysis. The selected patients were divided into a Candida group and a non-Candida group according to the presence or absence of Candida as the causative organism. Fifty-six (4.1%) of 1379 patients were diagnosed with IAIs after gastrectomy. Fifty-two patients were included based on culture analyses. A total of 111 strains and 28 bacterial species were isolated in the initial culture test. Candida constituted 7.2% of all the 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-E2 human rotaviruses in the Tokyo metropolis, Japan in 2018 has been reported. During rotavirus strain surveillance in different regions of Japan (Mie, Okayama, and Chiba prefectures), G9P-E2 strains were detected in diarrheic children in all three prefectures. Here, we characterized the whole genomes of seven representative G9P-E2 strains. On full-genome-based analysis, the seven study strains exhibited a unique genotype configuration having the NSP4 gene of genogroup 2 in a genogroup 1 genomic backbone: G9-P-I1-R1-C1-M1-A1-N1-T1-E2-H1. This genotype constellation is shared by Tokyo G9P-E2 strains. Phylogenetic analysis showed that all the 11 genes, except the NSP4 one, of the seven study strains appeared to have originated from co-circulating Wa-like G9P-E1 strains. On the other hand, the NSP4 gene appeared to have originated from co-circulating DS-1-like G2P-E2 strains. Thus, these study G9P-E2 strains appeared to be derived through reassortment between G9P-E1 and G2P-E2 strains in Japan. Notably, the seven study G9P-E2 strains and Tokyo G9P-E2 strains were revealed to have 11-segment genomes almost indistinguishable from one another in their sequences (99.3-100%), indicating all these G9P-E2 strains had a common origin. To our knowledge, this is the first description of the rapid spread of G9P-E2 strains across a country.
Respiratory infections are common diseases, the most common causative agent is a virus. In case of novel viral diseases pandemic like the COVID-19, routinely surveillance of respiratory viruses is useful. In this study, to clarify what kind of virus is involved in suspected cases of COVID-19 in the early stages of the pandemic, we attempted to detect various respiratory viruses from 613 specimens that tested negative for SARS-CoV-2 using RT- PCR method. Viruses were detected from 59 (9.6%) patients. Human rhinovirus (HRV), human metapneumovirus (HMPV), human respiratory syncytial virus, and human parechovirus were detected in 29 cases, 25 cases, 3 cases, and 2 cases, respectively. Although this study was conducted in 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 in the early stages of a pandemic, such as COVID-19. Because various respiratory viruses maintain a constant effect during the outbreak of the newly emerged pandemic respiratory virus, to make good use for clinical and public health, from normal period systematic surveillance about respiratory viruses is needed.
Candida auris, first described from an ear infection in Japan, is the most talked about multidrug resistant emerging pathogenic fungal species. Its environmental niche remained a mystery until its first isolation from wetlands of the Andaman Islands, India in 2020. We screened a subset of the world’s largest sequence repository, the Sequence Read Archive at NCBI using a DNA metabarcoding approach, based on either the ITS1 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.
Over the past few decades, understanding of the clinical features of pulmonary cryptococcosis (PC) has progressed, yet there is a lack of data on the manifestations of PC over time. To investigate the differences in clinical characteristics of PC across different time periods, we performed a retrospective review of 130 non-AIDS patients diagnosed with pathologically or microbiologically confirmed PC from 1990-2020. Among 130 PC patients, 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 patients (57.7%) underwent surgery alone. PC clinical features at different time periods showed that hospitalization days decreased (P=0.009), and patients with symptoms decreased over time. Patients exhibiting isolated lesions decreased (P=0.022), and patients exhibiting subpleural lesions increased (P=0.020). Patients with lesions presenting 3-10 mm nodules increased (P=0.028). In conclusion, more and more patients have been diagnosed of PC in the last 30 years. The timing of PC diagnosis has shifted to early in disease progression. Pulmonary lesions caused by cryptococcosis are easily misdiagnosed and may lead to unnecessary surgical treatment. Further research is needed to identify lung lesions caused by cryptococcosis.
Comparative validation data and clinical performance data are essential for the reliable interpretation of SARS-CoV-2 antibody test results. This study aimed to assess the performance of six SARS-CoV-2 IgG immunoassays in different disease severity settings. Four automated chemiluminescence immunoassays Access (Beckman Coulter), Architect (Abbott), Atellica-IM (Siemens) and Elecsys (Roche) and two ELISA assays (SARS-CoV-2 IgG-S1-based and NCP IgG, Euroimmun) were evaluated in 143 patients and 50 pre-pandemic control sera. Accuracy and precision tests were performed for validation. Overall sensitivity differed between 73.38-88.65%, being higher in spike protein-based assays. Specificity was ≥ 98% in all immunoassays. IgG response was lower for the samples taken <20 days post-symptom onset (87.30%) than for the samples taken ≥20 days post-symptom onset (94.80%). Higher rate of antibody was detected in the clinically moderate disease group.In the asymptomatic and mild group more antibody positivity was detected with spike protein-based assays. Clinical performance of the immunoassays differs according to disease severity and antigen targeted; moderate disease leading to highest rate of IgG response. All the assays tested were eligible for the detection of SARS-CoV-2 IgG however, spike-based assays revealed relatively higher sensitivity than the nucleoprotein-based assays particularly in the asymptomatic and mild disease severity.
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 six friends and 15 colleagues, of whom five friends and 13 colleagues underwent interferon-ã release assay (IGRA). Of these, three friends (60.0%) and four colleagues (30.8%) were IGRA-positive. Each one 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 officer(s) 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.
The causative agents of leprosy are Mycobacterium leprae and Mycobacterium lepromatosis. M. lepromatosis was found in 2008 to cause diffuse lepromatous leprosy in Mexican patients. The objective of this work was to identify M. leprae and M. lepromatosis in paraffin-embedded skin samples from Caribbean leprosy patients.A total of 6 skin samples were obtained from the Dominican Republic. All cases presented the multibacillary form; 5 cases were nodular lepromatous leprosy, and 1 case was borderline lepromatous leprosy. All patients received multidrug therapy. Molecular identification was achieved using the M. leprae-specific repetitive element (RLEP) for M. leprae and the hemN gene for M. lepromatosis. Mycobacterium leprae was identified in two lepromatous leprosy cases and 1 borderline lepromatous leprosy case; M. lepromatosis was found in 1 nodular lepromatous leprosy case. Both Mycobacterium species were present in two nodular lepromatous leprosy cases. This is the first report of M. lepromatosis in the Dominican Republic.
For maintaining the performance quality, HIV in-vitro diagnostic (IVD) kits are required to be evaluated by unbiased health regulatory organisation following predefined guidelines. WHO prequalification is one such program for evaluation of in-vitro diagnostic assays. In present systematic review and meta-analysis, we analysed and compared seventeen WHO prequalified public reports of HIV IVDs to yield summarised information for performance parameters. Pooled sensitivity, pooled specificity, Positive Likelihood Ratio (PLR), Negative Likelihood Ratio (NLR) and diagnostic odds ratio (DOR) were used as overall performance evaluation parameters. High (≥98%) and comparable level of sensitivity and specificity were observed for most of the assays. The overall diagnostic efficiency was observed to attain high precision as evident by the value of Area under the curve (AUC) for the hierarchical summary receiver operating characteristic (HSROC) curve (AUC≥0.98).
Novel immunodominant antigens are urgently required for diagnosis and vaccine of Helicobacter pylori(HP). FliD, an important colonization factor was cloned and expressed(rFliD) to evaluate the levels of specific-IgG, IgM and IgA antibodies in the serum of patients by ELISA. Rabbit anti-rFliD polyclonal antibody (pAb) was obtained by subcutaneous injections of rFliD. The rFliD-specific IFN-γ and IL-4 of peripheral blood mononuclear cells and CD4+ T cells from human were analyzed by 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 compared with 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 in the immunohistochemical analysis of gastritis and gastric cancertissues 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 T helper type 1-dominant subtype. These findings indicate that rFliD exhibits high validity as a biomarker in HPdiagnosis and may also be a potent antigen for vaccine design due to its high cellular and humoral immune response.
The detection of other pathogens in hospitalized coronavirus disease (COVID-19) patients are reported to be infrequent. Considering that the data from Japan is limited, we conducted an observational study including hospitalized COVID-19 patients at the National Center for Global Health and Medicine from January to September 2020. In total, 247 COVID-19 patients were studied. Rapid diagnostic tests such as immunochromatography were performed in 31 (12.6%). Filmarray Respiratory Panel was performed in 18 (7.3%) patients, and none of the tests were positive for pathogens other than severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Respiratory bacterial culture was performed in 66 (26.7%) patients, gram-positive bacteria were identified in 8 (12.1%) patients; gram-negative bacteria, 7 (10.6%) patients, and normal flora, 63 (95.5%) patients. Patients for whom culture was performed were older, more severely ill, and more likely to have radiological evidence of pneumonia on admission. Culture was more frequently performed in the early period of the epidemic than in the later period, without differences in bacterial detection rates. The proportion of viral and bacterial detections among hospitalized COVID-19 patients in tertiary care hospitals in Japan was low. A larger cohort study is necessary to evaluate the effects of each pathogen on the clinical course of COVID-19.
Severe fever with thrombocytopenia syndrome (SFTS) caused by Dabie bandavirus (formerly SFTS virus, SFTSV), which belongs to the Bandavirus genus (formerly Phlebovirus genus) of the Phenuiviridae family (formerly Bunyaviridae family) is a tick-borne novel bunyavirus infection with high case fatality. A 4-year-old dog sickened with symptoms of lethargy and anorexia was diagnosed as having SFTSV infection virologically in western Japan in June 2017. The dog’s owner, a man in his 40s, had taken care of the sick dog and became sick 10 days after disease onset in the dog, showing symptoms such as fever, arthralgia, headache, and nausea and vomiting. Total blood cell counts revealed leukocytopenia and thrombocytopenia. He was treated on an outpatient basis. He had no scars suggesting that he had been bitten by tick and was diagnosed as having SFTS by detection of IgM and neutralizing antibodies to SFTSV. The patient was infected with SFTSV directly from the SFTSV-infected dog. Humans can be at risk of SFTSV infections through direct contact with sick dogs infected with SFTSV.
Prominent genomic recombination has been observed between the Delta and Alpha variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) isolated from clinical specimens in Japan. Interestingly, the recombination variant detected in this study carries a spike protein identical to the one in the domestic Delta variant, thereby suggesting that further risks would not be concerned with infectivity and immune escape. The recombinant has been classified as XC lineage in the PANGOLIN database. It is necessary to intensively study such marked genetic variations and characterize the emerging variants after careful verification of their lineage and clade assignment.
Genus Plesiomonas, represented by a single species, P. shigelloides is a Gram-negative bacillus associated with gastrointestinal and extraintestinal disease in humans. In this study, 44 clinical isolates (gastrointestinal n=41; extraintestinal n=3) were genetically confirmed as P. shigelloides using the hug gene. All 20 virulence genes were detected in gastrointestinal isolates, ranging from 7.7% to 100%, however, only 12 genes were detected in extra-gastrointestinal isolates, ranging from 33.3% to 100%. The phlA gene was significantly (p=0.0216) associated with gastrointestinal isolates. The results of this study suggest that the presence of phlA may play a role in gastrointestinal-related infections. On the other hand, pilF, tolC and fur were detected in both gastrointestinal and extraintestinal clinical isolates and further investigations are warrants to elucidate their role in the pathogenesis of P. shigelloides.
We describe a domestic case of retropharyngeal abscess (RFA) in a child caused by a community-acquired Methicillin-resistant Staphylococcus aureus (CA-MRSA) isolate that was genetically proven to be USA300 clone (ST8-SCCmec IVa- Panton-Valentine leukocidin (PVL )). USA300 generally has a PVL gene, epidemiologic association with severe and recurrent skin and soft tissue infection, and is the leading cause of RPA in the United States. A 1-year-old previously healthy girl visited the emergency department for fever, sore throat, and refusal to move her neck. There was no recent medical exposure or history of travel abroad. An enhanced computed tomography revealed bulky low-density area with ring enhancement on retropharyngeal space and right parapharyngeal space. MRSA was isolated from the pus obtained from surgical drainage, and antibiotics were continued for a total of 21 days. The MRSA was analyzed by whole genome sequencing and compared with the representative USA300 isolates. The stain was typed as ST8-t9829-SCCmec IVa with PVL and ACME, and the sequence was 99.8 % identical to USA300 isolates. The present case supports the possibility that USA300 is potentially spreading in the Japanese community, and raises alarm for the possibility of USA300 invasive infections without a clear route of infection.
Sphingomonas paucimobilis is an aerobic, nonfermentative, opportunistic Gram-negative bacilli, and can be found in water systems. This study was conducted for analyzing concurrent S. paucimobilis bacteraemia cases and treatment outcomes, investigation of potential outbreak sources, and antimicrobial resistance profiles. This was an ambidirectional cohort study conducted in a 30-bed pediatric haematology/oncology hospital. Patient ages ranged from 1 to 17 years, with a median age of 5 years. Environmental sampling for outbreak source investigation was applied. Bacterial identification and antimicrobial susceptibility tests of isolated bacteria were done using the disk diffusion method and the Vitek®2 automated system. S. paucimobilis was detected in a total of 181 blood culture samples of 51 patients over two years and was isolated from hot tap water. 66% of patients were followed up with the diagnosis of Acute lymphoblastic leukemia (ALL) and two of our patients with ALL died due to S. paucimobilis sepsis. S. paucimobilis isolates were generally susceptible to carbapenems and quinolones. Surveillance and epidemic control should be done for hospital-acquired infectious agents such as S. paucimobilis. Water distribution systems should be checked against colonizing agents at regular intervals.
Severe fever with thrombocytopenia syndrome is an emerging hemorrhagic fever disease with high mortality. Severe cases progressed rapidly, with deaths occurring within two weeks. Therefore, the construction of a model to predict the disease progression among hospitalized SFTS infected patients plays an important role in clinical practice. The development cohort including 121 SFTS patients, 25 were severe and 96 were mild. 2 of the 64 variables were independent risk factors, including neurological symptoms (OR, 12.915; 95% CI, 3.342-49.916; P<0.001) and AST/ALT levels (OR, 1.891; 95% CI, 1.272-2.813; P=0.002). The AUC of the model was 0.882 (95%CI: 0.808-0.956). The mean AUC value obtained from internal validation was 0.883 (95%CI: 0.809-0.957). The AUC in the external validation cohort was 0.873 (95%CI: 0.775-0.972).This model can be used for helping identifying severe patients as early as possible with high predictive value, stability, and repeatability. This model can help clinicians in their treatment plan making.
The World Health Organization (WHO) designated Omicron (B.1.1.529 lineage) of SARS-CoV-2 as a new variant of concern (VOC) on 26th of November 2021. The risk to public health conferred by the Omicron variant is still not completely clear, although its numerous gene mutations raise concern about its potential for increased transmissibility and immune escape. In this study, we describe our development of two single nucleotide polymorphism (SNP) genotyping assays targeting the G339D or T547K mutation of the spike protein for screening of the Omicron variant. A specificity test revealed that the two assays successfully discriminated the Omicron variant from the Delta variant and Alpha variant each with one nucleotide mismatch. In addition, a sensitivity test showed that the G339D and T547K assays detected at least 2.60 and 3.36 RNA copies of the Omicron variant, respectively, and 1.59 RNA copies of the Delta variant. These results demonstrated that both assays could be useful for detecting and discriminating the Omicron variant from other strains. In addition, because of the rapid and unpredictable evolution of SARS-CoV-2, combining our assays with previously developed assays for detecting other mutations may lead to a more accurate diagnosis system.
The new epidemic coronavirus SARS-CoV-2 is responsible for severe respiratory illness (i.e. COVID-19). RT-PCR on respiratory samples is the gold standard in COVID-19 diagnosis, while serological tests may contribute to detect post-infection and post-vaccination immunity, and permit seroprevalence studies. The lateral flow immunoassay (LFIA) COVIDTECH® SARS-CoV-2 IgM/IgG Antibody Rapid Test that detects anti-SARS-CoV-2 IgM and IgG using a S-protein recombinant antigen has been independently evaluated in two laboratories. The specificity evaluated on 65 pre-pandemic samples reached 100% for IgM/IgG. Analyzing samples from patients with RT-PCR-confirmed infection, IgM/IgG antibodies were detected in 18/26 (69%) and 58/58 (100%) samples before day 13th and from the 14th day post-symptom onset respectively. Before the 14th post-symptom onset, the COVIDTECH test was less sensitive than another LFIA method (BioSynex BSS IgM/IgG) and a chemiluminescent Immunoassay (LIAISON® SARS-CoV-2 TrimericS IgG assay). Overall, this LFIA method is suitable for SARS-CoV-2 serological diagnosis, when the patient is > 14th day after onset of symptoms.
The coronavirus disease 2019 (COVID-19) pandemic caused severe health impacts to worldwide. The aim of our study was to provide suggestions for government to manage serious infectious disease outbreaks in remote regions with relatively poor medical resources. The basic reproduction number (R0), incubation period, time from symptom onset to confirmed and duration of hospitalization were analyzed. We compared the composition of imported and local secondary cases, and cases with mild/common and severe/critical illness according to age, sex, and clinical symptoms. From January 23 to February 19, 2020 (less than 1 month), 75 local COVID-19 cases were confirmed in Inner Mongolia. Among them, the median age was 45.0 years and 33 (44.0%) were imported. More than 80.0% cases were mild/common. The case fatality rate was 1.3% and the R0 was estimated to be 2.3. The median incubation period was 8.5 days. There was a significant difference in the incubation period between imported and local secondary cases (P<0.001). The early and mandatory control strategies implemented by government were associated with a rapid reduction in COVID-19 incidence in Inner Mongolia.
Accurate monitoring of epidemics is a key strategy for the control of human immunodeficiency virus type-1 (HIV-1) infection. To delineate the characteristic of newly-diagnosed cases of HIV-1 infection, we assessed the proportion of recent HIV-1 infections using a recent infection testing algorithm (RITA). In 2015, 248 cases were newly diagnosed with HIV infection in Reginal Hospital Koforidua, Ghana. Of these, 234 cases (94.4%) were infected with HIV-1 only, four (1.6%) were infected with HIV-2 only, and 10 (4.0%) were co-infected with HIV-1 and HIV-2. All the HIV-1 single seropositive samples were applied to HIV-1 LAg avidity assay for RITA. Our analysis revealed that 18 cases (7.7%) were determined as recent infections, indicating that early diagnosis has not been achieved in Ghana. This is the first report assessing the proportion of recent infections in Ghana using a biomarker approach. Accumulation of these data would contribute to accurate estimation of HIV-1 incidence and prevalence in Ghana.
Antimicrobial resistance (AMR) is a threat to patient health. However, there is a lack of data for optimizing antimicrobial use. Furthermore, reducing antibiotic use raises concerns regarding patient safety; there is controversy regarding its effectiveness in reducing AMR prevalence. Researchers at the Japanese Red Cross Ishinomaki Hospital (JRCIH), the only tertiary care hospital in the medical zone, along with local medical and pharmacy associations and public health centers, has been leading the AMR control program since 2018. The program involves lectures aimed at optimizing antimicrobial use, regular publication of surveillance data of drug-resistant strains at the JRCIH, and presentation of first-line treatments for community-acquired infections. Delivery of oral antimicrobials across the region in 2020 was 28.7% lower than that in 2013, with delivery of cephalosporins, quinolones, and macrolides dropping by 34.8%, 46.8%, and 56.0%, respectively. Despite these reductions, there has been no associated increase in the number of patients with severe infectious diseases admitted to the JRCIH. The rates of representative drug-resistant strains bacteremia, such as extended-spectrum beta-lactamase-producing Escherichia coli and methicillin-resistant Staphylococcus aureus, reduced by half. Herein, we demonstrated the potential of collaborative efforts to optimize antimicrobial agent use and reduce AMR prevalence without compromising patient safety.
There have been many reports on the effectiveness of various disinfection methods for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and their applicability to the disinfection of N95 respirators and surgical masks. To date, there have been no reports on the decontamination of the intermediate layers. In this study, the conditions required for the decontamination of such layers were set by simulation considering the thickness and shape of the N95 respirators or surgical masks (samples). After applying heat (steam, dry heat, or hot water) at 75°C for 60 min or chemical (benzalkonium chloride or laundry detergent) treatment, the collection efficiency of the samples was checked and evaluated. After the dry heat treatment, the time between treatment and when the heat reached the intermediate layer of the filter fiber was extended by 10 min. A dry heat disinfection method that combines hot water and a closed container was also evaluated, and satisfactory conditions were extended by 60 min. For each heat treatment, there was almost no effect on the collection efficiency, although there were cases where deformation was caused by mechanical stress. In contrast, chemical treatment resulted in a reduction in the collection efficiency of smaller particles.
Herpes simplex virus 1 (HSV-1)-TK(8UAG) expresses a truncated thymidine kinase (TK) translated from the second initiation codon due to a stop UAG codon at the 8th position (counted from the first initiation codon). Here, we showed that the sensitivity of HSV-1-TK(8UAG) to acyclovir (ACV) is similar to that of control HSV-1 wild-type (WT), which expresses an intact TK protein. However, HSV-1-TK(44UAG), which expresses a truncated TK due to a UAG codon at position 44, showed lower sensitivity to ACV. A mouse infection model was used to compare the virulence of HSV-1-TK(8UAG) and HSV-1-TK(44UAG) with that of HSV-1 wild-type (WT). The 50% lethal dose (LD50) value of HSV-1-TK(44UAG) was 7.8-fold higher than that of HSV-1-TK(8UAG), whereas the LD50 value of HSV-1-TK(8UAG) was the same as that of the parental HSV-1 WT. There were no statistically significant differences between HSV-1-TK(44UAG), HSV-1-TK(8UAG), and HSV-1 WT with respect to replication capacity and viral TK mRNA expression in mouse brain. Thus, the virulence of HSV-1 expressing a truncated viral TK translated from the second initiation codon might depend on the position of the UAG stop codon.
Azithromycin is one of the antibiotics used to treat syphilis, especially in the context of penicillin allergy. Resistance to azithromycin is widely reported associated with one and/or two point mutations on the 23S rRNA gene but has yet to be described in Indonesia. Specimens were collected from 220 patients diagnosed with secondary syphilis. A multiplex nested PCR testing system using the 23S rRNA target gene of Treponema pallidum was designed using three pairs of primers. The first step used PCR pairs of primers to detect T. pallidum. In the second step of PCR using 2 pairs of primers were achieved to identify azithromycin resistant T. pallidum based on A2058G and A2059G point mutations. There was no T.pallidum identified resistant to azithromycin in Jakarta and Bandung. T. pallidum resistance to azithromycin were found in Makassar, Medan, and Bali. The majority of azithromycin resistance was found among heterosexual males and in patients living with HIV. This study has demonstrated T. pallidum resistance to azithromycin in Indonesia appears to be a novel variant of resistance, containing both the A2058G and A2059G mutations that was found in Medan and Makassar.
Circulation of avian influenza A viruses in poultry is a public health concern because these viruses may cause severe disease in humans and have the potential to become more transmissible among humans. Monitoring the susceptibility of these viruses to antivirals is important for influenza pandemic preparedness. However, information about their antiviral susceptibility is limited. Here, we determined the susceptibilities of avian influenza A(H5N1), A(H5N2), A(H5N8), A(H7N7), A(H7N9), A(H9N1), and A(H9N2) viruses isolated in Japan to the antivirals approved for use there: the M2 inhibitor amantadine; the neuraminidase inhibitors oseltamivir, peramivir, zanamivir, and laninamivir; and the RNA polymerase inhibitors baloxavir and favipiravir. Genotypic methods that detect amino acid substitutions associated with antiviral resistance and phenotypic methods that assess viral susceptibility to drugs revealed that these avian influenza A viruses are susceptible to neuraminidase inhibitors and RNA polymerase inhibitors. These results suggest that the neuraminidase inhibitors and the RNA polymerase inhibitors currently approved in Japan could be a treatment option against influenza A virus infections in humans.
We are yet to completely understand the transmission dynamics of COVID-19 which is a highly infectious disease and research exploring the same is lacking. Hence, a community-based cross-sectional study was conducted aiming to assess the intra-familial transmission pattern among the rural residents of Ahmedabad, Gujarat in relation to possible determinants with special focus on viral load as an important determinant. A cross-sectional study was done where 195 families were visited. Families having at least one infected case, were interviewed. Information about their socio-demographic profile and secondary transmission of case/s were recorded. Out of 195, 114 families confirmed to having at least one infected case within the family. About 38.6% (44/114) of the index cases were asymptomatic, which was much higher among low viral load index cases. Index cases with high, moderate and low viral load had transmitted the infection with an average of 3.3, 1.5, 0.4 secondary cases per index case respectively. About one third of COVID-19 infected cases was asymptomatic and was capable of spreading the disease within families. Secondly, index cases with higher viral load had higher transmission potential to generate more secondary cases compared to low viral load.