JAPANESE JOURNAL OF INFECTIOUS DISEASES

The characteristics of cardiac injury in patients with severe fever with thrombocytopenia syndrome
Sun J, Hao Y, Niu J, Du Z and Yang J
This research sought to delineate the characteristics of cardiac injury in individuals diagnosed with severe fever with thrombocytopenia syndrome (SFTS) and to ascertain its relationship with prognosis. A retrospective analysis was conducted in 324 patients diagnosed with SFTS between January 2021 and December 2023, patients were categorized into survival and non-survival groups. Univariate and multivariate analyses identified significant indicators and predicted mortality risk factors. Statistically significant differences between the two groups were found in various parameters: age, history of hypertension, presence of diarrhea, petechiae, neurological abnormalities, and numerous laboratory measures. These included lymphocyte, monocyte, and platelet counts, as well as levels of liver enzymes, kidney function markers, cardiac biomarkers, clotting factors, inflammatory markers, Dabie Banda virus RNA, heart rate, PR interval, QT interval and incidence of ST depression. Age, history of hypertension, neurological abnormalities, Cr, PT and QT intervals as independent risk factors for mortality. The incidence of viral myocarditis in patients with SFTS was 64.12%, the non-survival group demonstrated a higher incidence of cardiac injury, which was both earlier and more severe. The incidence of viral myocarditis in patients with SFTS is closely related to the prognosis.
Detection of Human Coronavirus-OC43 in Nasopharyngeal Swab Specimens Via Immunofluorescence Staining Using Human Serum and an Anti-human Antibody
Yamaya M, Watanabe O, Kitai Y, Sayama Y, Ohmiya S and Nishimura H
Immunofluorescence methods using cell lines to detect seasonal human coronavirus (HCoV)-OC43 in nasopharyngeal swab specimens have not yet been established. A human rectal adenocarcinoma cell line (HRT-18) was exposed to the specimens obtained from patients with upper respiratory tract infections. Immunofluorescence staining was conducted using a combination of human serum containing an HCoV-OC43 anti-spike protein antibody and a fluorescence-labeled anti-human antibody. Positive staining in HRT-18 cells was detected after exposure to specimens obtained from nine of eleven patients in whom HCoV-OC43 RNA was detected using the FilmArray method. Increased viral RNA levels in the supernatant were also detected in HRT-18 cells exposed to specimens obtained from four of five patients. In contrast, positive staining was not detected in HRT-18 cells exposed to six patient specimens that tested negative for RNA from 17 types and subtypes of respiratory viruses, including HCoV-OC43. Cells inoculated with the established strain HCoV-OC43 (ATCC VR-759) also showed positive staining. These findings suggest that replication-competent HCoV-OC43 in the specimens can be detected via immunofluorescence staining of HRT-18 cells with human serum. Using this method, positive staining for viruses other than HCoV-OC43 may be obtained.
Microbiological characteristics and drug resistance rates of Candida auris isolates in Japan
Abe M, Koizumi A, Umeyama T, Tomuro H, Muraosa Y, Nakayama N, Oiki S, Shimada S, Murakami Y, Ota M, Yoshimi I, Takahashi A, Ono T, Sasaki M, Uchida-Fujii E, Nakashita M, Kurosu H, Yamagishi T, Shinohara T, Hoshino Y and Miyazaki Y
Candida auris (C. auris) was initially isolated from a Japanese patient, and this species is an emerging fungus nowadays owing to its long-term colonization capabilities and high resistance to antifungal drugs. However, accurate domestic epidemiology of C. auris remains unknown. We here collected C. auris isolates reported from hospitals, public health centers, and public health institutes based on the administrative liaison. Moreover, we collected stocked C. auris isolates from three nongovernmental laboratory companies. Seventy C. auris isolates were collected during the study period. C. auris isolates predominantly originated from ear discharge clinical samples. Clade determination based on ITS-D1/D2 regions and CauMT1 locus revealed that almost all isolates belonged to clade II; however, one ear discharge-derived isolate belonged to clade I. Whole genome sequencing also confirmed this clade I C. auris isolate. Regarding drug susceptibilities, 20% of isolates were resistant to fluconazole; however, no isolates exhibited polyene or echinocandin resistance. Therefore, C. auris isolates in Japan were generally derived from ear discharges and belonged to clade II. However, ear discharge-derived isolates may not exclusively belong to clade II. Although no invasive cases were reported during the study period, continuing surveillance program for describing clear domestic epidemiology would be necessary.
Non-woven Masks and SARS-CoV-2 Infection in a Cluster Setting in Japan
Takahashi Y, Takao S, Kadowaki T, Matsumoto N and Yorifuji T
Evidence regarding the types of masks that are effective in preventing infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is limited. We identified the mask types that were effective against SARS-CoV-2 infection in a cluster setting in Japan. Data from a cluster of employees with coronavirus disease 2019 at a manufacturing company in mid-August 2021 were retrospectively reviewed. A total of 87 employees who reported the type of mask worn were included. The types of masks were dichotomized into non-woven masks or other types of masks, such as cloth or urethane masks. The association between mask type and SARS-CoV-2 infection was determined using logistic regression analysis after adjusting for potential confounders. Participants who wore non-woven masks were less likely to be infected with SARS-CoV-2 (9.7%) than those who wore other types of masks (26.7%). After adjusting for potential confounders, wearing a non-woven mask was significantly associated with a reduced risk of infection compared to wearing other types of masks (odds ratio, 0.10; 95% confidence interval, 0.01-0.80). Non-woven masks were more effective in preventing SARS-CoV-2 infection in a cluster setting than other types of masks, such as cloth or urethane masks.
Seroprevalence of eight viruses and pertussis in pregnant women at a regional hospital in Japan in 2022: Comparison with previous studies
Takemoto K, Nishimura N, Kuriyama H, Kondo Y, Sugiura M, Umehara M, Akano T, Watarai M, Ochiai K, Mimatsu H, Gotoh K and Ozaki T
This study evaluated the prevalence of antibodies against eight viruses and pertussis in the serum collected from 191 pregnant women in 2022. Serum IgG antibodies against the following viruses and pertussis toxin (PT) were measured: measles virus (MV), rubella virus (RV), mumps virus (MuV), varicella-zoster virus (VZV), herpes simplex virus (HSV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), and human parvovirus B19 (PVB19). Infection history and immunization status were simultaneously obtained using a survey questionnaire for vaccine-preventable diseases of measles, rubella, mumps, varicella, and pertussis. Our results were compared with those of our previous studies using umbilical cord blood samples in 2001-2002 and 2013 for eight viruses and a 2016-2018 study for pertussis. Seroprevalence data in 2022 were 88.5% for MV; 86.4% for RV; 46.1% for MuV; 91.1% for VZV; 47.6% for HSV; 61.3% for CMV; 93.7% for EBV; 69.6% for PVB19 and 63.4% for PT. The seroprevalence of all diseases, except for PVB19 and pertussis, continued to decline over time. The mean IgG antibody titers were significantly lower and the vaccination coverage rates were significantly higher in four vaccine-preventable viral diseases than previous results. Thus, trends in seroprevalence status for these pathogens should be monitored in pregnant women.
Utilizing Infectious Disease Surveillance for Epidemic Warnings of Respiratory Syncytial Virus Infections in Japan from 2015 to 2019
Ohta A, Hashimoto S, Kawado M, Oba MS, Uehara R, Taniguchi K, Sunagawa T, Nagai M and Murakami Y
Japan's National Epidemiological Surveillance of Infectious Diseases (NESID) has implemented a warning system for detecting epidemics in smaller districts, such as public health center (PHC) areas. This system is applied to influenza and pediatric infectious diseases. Respiratory syncytial virus (RSV) infection is not included but its incorporation is needed for effective early epidemic detection. We aimed to propose criterion values for an epidemic warning system related to RSV infection within PHC areas. We analyzed the weekly number of RSV infection cases reported by sentinel medical institutions (SMIs) in the NESID from 2015 to 2019. Weekly cases per SMI in the PHC area were set to establish an index for epidemic warnings. We determined criteria for issuing an epidemic warning by identifying distribution percentiles within the index. Setting the critical values for the onset and end of the epidemic warning at 5 and 2, respectively, yielded an approximately 5% annual proportion of PHC areas with an epidemic warning, which aligns with previously accepted frequency criteria for epidemic warnings. The 5-year (2015-2019) RSV infection epidemic trend showed that the set critical values were appropriate. Using these values could assist with issuing warnings regarding potential RSV infection epidemics in Japan.
Long-Term Immunity after Vaccination against Yellow Fever in Korean Travelers
Um J, Nix CD, Messer WB, Zhu Y, Park JS, Collins MH and Chin B
Although a live-attenuated yellow fever (YF) vaccine is known to elicit durable immunity, antibody titers may wane after vaccination. This study evaluated long-term immunity after vaccination against YF among individuals who resided in Korea and were vaccinated with YF virus- 17D prior to international travel. Serum was collected between December 2018 and December 2019 at the National Medical Center, Republic of Korea, from YF vaccine recipients who had been vaccinated for more than five years prior to sample collection. Long-term immunity against YF was assessed using three serological assays: IgG enzyme-linked immunosorbent assay (ELISA), immunofluorescence assay (IFA), and the focus reduction neutralization test (FRNT). Sixty-seven patients were enrolled in this study. The overall positivity rates for 50% focus reduction neutralization test (FRNT ), IFA, and ELISA in a time-variable cross-sectional sample of the cohort were 97.0%, 86.6%, and 26.9%, respectively. While 93.8% (15/16) of samples collected ≥10 years post-vaccination remained positive by FRNT , a significant inverse correlation was observed between FRNT titer and interval after vaccination (R = - 0.385, P = 0.001). Humoral immunity against YF was well preserved among Korean individuals who were vaccinated more than five years ago. IFA testing yielded results similar to those of FRNT testing, which may justify the further development of IFA to screen for waning immunity among those with previous YF vaccination.
Evaluation of the shortened quarantine policy among healthcare personnel in the cancer center setting during the Omicron epidemic in Japan: A descriptive epidemiological study
Kudo-Nagata Y, Ozawa T, Watanabe T, Sakurada M and Sekiya N
Updating and evaluating facility-based guidance in cancer centers for managing healthcare personnel (HCP) with close contact with individuals with coronavirus disease 2019 (COVID-19) is challenging because these settings are typically excluded from general guidance, and practical data on this population are limited. This study aimed to describe whether apparent outbreaks occurred under the updated protocol in the real-world setting of a cancer center. From July 2022 to January 2023, 402 HCP who had close contact with an individual with COVID-19 were identified and divided into two groups: the separation group, which underwent a five-day quarantine with physical isolation (172 HCP), and the cohabitation group, which followed a ten-day quarantine (227 HCP). A nucleic acid amplification test (NAAT) was conducted the day before the HCP returned to work. Data from their medical records were retrospectively collected and analyzed. As a primary outcome, no outbreaks due to post-quarantine transmission from close-contacted HCP were observed throughout the study period in either group. Our findings suggested a 5-day quarantine for HCP with close contact with COVID-19 might be applicable in cancer center settings if combined with NAAT before returning to work without increasing the risk of apparent outbreaks.
Mesocestoides vogae infection in dogs: confusion with echinococcosis
Morishima Y and Sugiyama H
We describe six independent cases of Mesocestoides infection in dogs presenting with diarrhea. Between November 2022 and August 2024, we were consulted by veterinarians regarding the identification of a species of small tapeworm excreted in dog feces. These veterinarians suspected the organism was Echinococcus multilocularis and believed it should be reported to health centers as a notifiable disease. Segmented and unsegmented worms, approximately 600 to 1,400 µm in length, were recovered from fecal samples. Microscopically, the worms had four suckers on the scolex but no rostellum. Subsequent molecular analysis of the mitochondrial cox1 and 12S rDNA genes revealed that all cases involved Mesocestoides vogae. Affected dogs were treated with an anthelmintic, and the diarrhea disappeared immediately. Perhaps due to the heavy infection load, the host animals developed diarrhea, and the parasite was likely expelled before reaching maturity. These small tapeworms with few proglottids could therefore confuse veterinarians.
Sensitivity evaluation of a modified real-time reverse-transcription PCR primer to detect a measles virus variant in Japan in 2024
Kurata T, Kanbayashi D, Kaida A, Morikawa S, Hiroi S, Hirai Y, Koyama M, Miyama T, Otsuki N and Motomura K
A measles outbreak occurred in Japan in February 2024 due to a measles virus variant that was imported from central Asian countries with three mismatches at the PCR reverse primer (MVN1213R) annealing site. To examine and improve the impact of real-time PCR effectiveness for detecting this variant, we compared the sensitivity of real-time PCR between MVN1213R and a modified primer using control RNAs, clinical isolates, and clinical specimens. The median difference in the cycle threshold value was 2.92 (interquartile range, IQR 1.99-3.38) lower using the modified primer compared with MVN1213R. Thus, PCR primer sets should be modified to effectively detect this measles virus mutation.
Evaluation of rapid amplicon-based nanopore sequencing using the latest chemistry for accurate whole genome analysis of influenza A virus in clinical samples
Kuba Y, Takemae N, Kawato S, Oba K, Taniguchi K and Kageyama T
MinION sequencing is widely used to sequence influenza A virus (IAV) genomes; however, the accuracy and utility of this approach, using the latest chemistry to obtain whole viral genome sequences directly from clinical samples, remain insufficiently investigated. We evaluated the sequencing accuracy of combining simultaneous multisegment one-step RT-PCR and MinION sequencing using various subtypes of 13 IAV isolates. The latest R10.4.1 chemistry significantly improved sequencing accuracy, achieving ≥99.993% identity with Illumina MiSeq results and reducing the single nucleotide deletion in homopolymer regions. Applying this method to 11 clinical samples enabled rapid subtype identification and the acquisition of eight full-length IAV genomes. In four of these samples, subtype identification of HA and NA was achieved within 20 min after the start of sequencing and a full-length IAV genome was obtained within 7 h after RNA extraction. However, there was concern that cross barcode misassignment during demultiplexing affected data interpretation, particularly for samples with low viral genome copy numbers. This approach can be used for the rapid identification of IAV subtypes and accurate acquisition of full IAV genome sequences from clinical samples, although careful data analysis is required for the multiplex sequencing of clinical samples with low viral genome copy numbers.
Detection of recombinant type of human adenovirus C composed of type 89 and type 5 in Aichi Prefecture, Japan, 2016-2019
Hirose E, Minagawa H, Adachi H, Suzuki M, Nakamura N, Saito N, Ito M, Mitsuoka C, Sato K and Yasui Y
Recombinant human adenoviruses (HAdVs) have been reported from many countries, including Japan. We report a recombinant HAdV-C type detected in feces with gastroenteritis infection or throat swabs with upper respiratory tract inflammation of six children in Aichi Prefecture. This type may have been prevalent in the area. Between April 2014 and March 2019, we attempted to detect HAdVs in 9,483 specimens (fecal, throat swab, urine, and conjunctival swab) collected from patients with suspected viral infection. A total of 220 HAdV-C isolates were obtained and serotyped by neutralization test (NT). Of these, 62 HAdV-C strains (HAdV-C1: 15, -C2: 19, -C5: 22, -C6: 6) were genotyped by sequencing for the three regions, penton base, hexon, and fiber regions, respectively. All 62 strains were grouped into the same genotype as serotype for the hexon and fiber region. In contrast, phylogenetic analysis showed 6 of the 22 strains with serotype HAdV-C5 were grouped into HAdV-C89 for the penton base region. This type was detected as a recombinant HAdV causing SARI in China between 2017 and 2021, was found to have been persistently detected in transnational Aichi Prefecture over the same period.
The Tokyo Metropolitan Government external quality assessment of SARS-CoV-2 nucleic acid amplification tests for clinics in 2023
Moriuchi R, Inaba R, Nagano M, Oda M, Shinkai T, Noguchi T, Sugishita Y, Nishizuka I and Ishii Y
An external quality assessment (EQA) on nucleic acid amplification tests for SARS-CoV-2 was conducted among clinics that introduced testing instrument through the Tokyo Subsidy Program for Facilities and Equipment for Testing in COVID-19 in 2023. The survey samples consisted of sample 1 (20,000 copies/mL), sample 2 (10,000 copies/mL), and negative sample. Results were obtained through Cycle threshold (Ct) values as well as positive-negative result determinations. On-site technical support was provided to the clinics that responded incorrectly. A total of 544 clinics (589 instruments) participated, and Abbott's ID NOW (82.2%) was the most widely used in this survey. The qualitative test results showed high correctness rates, 95.2% for sample 1, 93.2% for sample 2, and 96.3% for negative sample. Differences in Ct values were observed among reagents and instruments. Technical support were provided to 63 clinics. It revealed that discrepancies of qualitative test were mainly due to deviations from the protocol instructions, mixing all three survey samples into one vial and errors caused by foaming. This survey was unique in that the participants were mostly end-users who were not laboratory testing specialists and mainly used point-of-care testing instruments. It is important to continue EQA to improve and maintain testing accuracy.
Monkeypox outbreak 2023 in Chengdu, China: an observational study
Rao L, Yang M, Chen LY, Chen LH, Lu YH, Wang Y and Feng YY
Monkeypox is a zoonotic viral disease caused by monkeypox virus infection and formerly this disease had been endemic mainly in Africa. Since May 2022, the disease has rapidly spread across the world and some imported case was confirmed sporadically in China. Under these circumstances, data of confirmed cases were collected consecutively in Chengdu, southwest China to investigate clinical and epidemiological characteristics. In this study, 28 male patients were confirmed to have monkeypox infection, with 26 identifying as MSM (men who have sex with men). Typical lesions included papules, pustular papules, vesicles, scabs and ulcerations. The most common sites of skin lesions were anogenital and perineal areas, three patients developed a widespread exanthem. Seven patients reported a history of sexual transmitted diseases, no one was hospitalized and there were no deaths. Three instances of secondary transmission were identified among close contacts, all of them were sexual partners of our participants. Furthermore, this observation provides insights of the public health for surveillance of this emerging disease and raises awareness among people at risk.
Seroprevalence of hepatitis A virus and hepatitis E virus antibodies in Madhesh Province, Dhanusha, Nepal
Rimal S, Shrestha S, Khadka A, Matsuda M, Suzuki R, Dumre SP and Pandey BD
Hepatitis A virus (HAV) and hepatitis E virus (HEV) are thought to have similar routes of transmission and epidemiology in developing countries. This study investigated the seroprevalences of these pathogens among healthy individuals in the Dhanusha district of Madesh Province, Nepal. Ninety serum samples collected between 2022 and 2023 were analyzed by enzyme-linked immunosorbent assay to detect immunoglobulin (Ig)G antibodies against HAV and HEV. Individuals (median age, 23 years; range, 1-45 years) were sorted into five age groups: 1-10, 11-20, 21-30, 31-40 and 41-45 years. Prevalences of HAV and HEV IgGs were 96.7% and 13.3%, respectively. All age groups showed very high positivity rates for HAV antibodies. In contrast, HEV infection rates were extremely low in children, and rapidly increased in adults >31 years old. No significant correlation was found between HAV and HEV seropositivity. Additional studies including other areas in Nepal are required for nationwide sero-surveillance against HAV and HEV.
Comparison of viral load in the nasopharyngeal swabs of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in different epidemic seasons in Gunma prefecture, Japan
Nakazawa Y, Tsukagoshi H, Shimada R, Kubota R and Saruki N
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has repeatedly undergone mutations since its emergence, based on which it has been assumed that there was a change in its characteristic, including virulence or antigenicity. In this study, we investigated the viral load in the nasopharyngeal samples of patients with SARS-CoV-2 in Gunma prefecture, Japan, from April 2, 2020, to April 1, 2023. The amount of virus in samples in the Omicron-variant-prevalent period was higher than that of strains detected in samples before week 50 of 2020, the B.1.1.284-prevalent period, the Alpha-variant-prevalent period, and the Delta-variant- prevalent period. Moreover, among Omicron variants, the sublineage BA.5-prevalent period showed higher amount of virus in the samples than BA.1-prevalent period and BA.2-prevalent period. Hence, the new variant may have been able to release more viruses into the nasopharyngeal samples during the process of repeated mutations, resulting in widespread infection. The amount of virus detected in the nasopharyngeal samples showed an increasing tendency with the evolution of the virus. Therefore, considering that the amount of virus in specimens is also vital factor contributing to the spread of infection, it is important to examine this factor in samples.
Long-term management of refractory vaginal trichomoniasis following initial metronidazole treatment failure: A case series
Maruki T, Ishikane M, Kurokawa M, Kubo T, Miyazato Y and Ohmagari N
Guidelines for sexually transmitted infections recommend oral metronidazole (MNZ) as the first-line treatment option for vaginal trichomoniasis; however, there have been cases of prolonged symptoms or recurrence after treatment. To consider appropriate treatment strategies for refractory vaginal trichomoniasis, we conducted a retrospective cohort study. We reviewed the medical records of patients who tested positive for Trichomonas vaginalis (T. vaginalis) at the National Center for Global Health and Medicine between August 2011 and May 2023. Refractory vaginal trichomoniasis was defined as the failure after the initial MNZ treatment. During the study period, nine cases of vaginal trichomoniasis were identified, six of which were refractory to treatment for T. vaginalis. Four patients were cured with a combination of oral and vaginal tinidazole (TNZ) therapy, one with oral TNZ and one with two doses of MNZ. Possible causes of treatment failure include MNZ-resistant T. vaginalis, reinfection between partners, and infections of other sexual transmitted diseases. However, the fact that TNZ was effective suggests that MNZ-resistant T. vaginalis may have been the cause. Although MNZ resistance testing was not performed in this study, treatment with TNZ should be considered in cases of refractory vaginal trichomoniasis, possibly caused by MNZ-resistant T. vaginalis.
Molecular detection of Mycobacterium leprae using RLEP-LAMP and restriction enzyme to ensure amplification specificity
Sharma M, Dwivedi P, Tripathi S, Patel P and Singh P
Early and accurate diagnosis of leprosy is important but remains a significant challenge till date. Loop-mediated isothermal amplification (LAMP) is an isothermal process for amplification of nucleic acids at constant temperature and has been used to develop field-friendly tests for many diseases. In the present study, we have described the development of a colorimetric LAMP assay targeting Mycobacterium leprae-specific 450 bp conserved region of the repeat sequences known as RLEP. Furthermore, the amplicons of LAMP were subjected to restriction analysis by the enzyme EcoRV for specificity. This method has the potential to become an accurate and efficient alternative to Sanger sequencing which is currently in use to validate the RLEP amplified products.
Detection of host vertebrate DNA in tick species collected from vegetation in Fukuoka, Japan
Kobayashi T and Ashizuka Y
Ticks are vectors of tick-borne diseases (TBDs) between humans and wild vertebrates. The relationship between ticks, host vertebrates, and their pathogens should be investigated for the effective control of TBDs. Hence, this study aimed to detect vertebrate DNA in ticks by using molecular methods and identify the species of such ticks collected in Fukuoka Prefecture, which is located in the northern Kyushu area of Japan. Ticks from vegetation were collected by flagging from 2017 to 2023. Out of 152 ticks collected by flagging, 65 (42.8%) were found to have vertebrate DNA. By stage, vertebrate DNAs were detected in 26 of 83 nymphs (31.3%) and 39 of 69 adults (56.5%). Among the host vertebrates, Sika deer was the main blood-feeding source of ticks in Fukuoka Prefecture. Owing to the widespread of deer across this prefecture, control of its population and other wildlife populations could be a countermeasure of reducing TBD risk.
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