Timing of #Remdesivir Initiation and Clinical #Outcomes in Hospitalized Patients with #COVID19 Who Are at High Risk of Disease Progression in #Japan: A Health Insurance Claims Database Study

 

Abstract

Early initiation of remdesivir (RDV) is recommended to improve COVID-19 outcomes, but real-world studies describing patterns of RDV use and related outcomes among Japanese COVID-19 patients at high-risk of severe outcomes or death are limited. This claims-based cohort study included 60,165 high-risk patients hospitalized with COVID-19 between October 2021 and June 2023 using the DeSC Healthcare claims database. Patients were categorized into early-RDV (within 2 days of hospital admission), late-RDV (between day 3 and day 7), and no-RDV groups based on RDV initiation timing. Descriptive analyses were performed according to RDV groups. Of the study patients, ≥85% were very elderly (≥75 years). Approximately 39% of patients received early RDV, 2% received late RDV, and 59% received no RDV. By day 28, the proportion of alive discharge for early-, late-, and no-RDV groups was 74.9%, 63.1%, and 71.8%, respectively. The mortality for early-, late-, and no-RDV groups was 7.7%, 8.8%, and 8.4%, respectively. Future hypothesis-driven studies with an appropriate adjustment for confounders are needed to formally evaluate the impact of RDV initiation timing on clinical outcomes in this high-risk, predominantly late-elderly population in Japan.

Source: 

Link: https://www.mdpi.com/1999-4915/18/4/479

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Impact of an #aminoacid #deletion detected in the #hemagglutinin (HA) #antigenic site of swine #influenza A virus field strains on HA antigenicity

 

ABSTRACT

Swine influenza A virus (swIAV) is an important pathogen with regard to both the swine industry and public health. The pandemic A(H1N1) 2009 outbreak was caused by the swine-origin pandemic A(H1N1) 2009 [A(H1N1)pdm09] virus. Several reports have shown that several amino acid substitutions in the hemagglutinin (HA) antigenic sites can alter HA antigenicity. However, the impact of the amino acid deletion at position 155 on HA antigenicity remains unknown. In this study, we have isolated 11 samples of swIAVs from seven pig farms in Japan and found an amino acid deletion at position 155 of the HA region in one of the isolates of the H1N2 subtype. To examine the impact of this amino acid deletion on viral replication and HA antigenicity, we generated recombinant influenza A viruses possessing the H1 HA gene encoding either an artificial insertion or deletion of glycine at position 155. The growth kinetics of these recombinant viruses in two different cell lines demonstrated that the effect of amino acid deletion at position 155 of H1 HA on viral replication is limited. In contrast, microneutralization assay-based neutralization titers revealed that amino acid deletion significantly altered HA antigenicity. These results demonstrate that a naturally occurring amino acid deletion at position 155 in an H1 HA antigenic site can markedly alter HA antigenicity with only a limited impact on replication in vitro, highlighting the need to monitor such variants in swine populations and to assess their zoonotic potential.

Source: 

Link: https://journals.asm.org/doi/full/10.1128/jvi.01820-25?af=R

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#Trends in #heart #failure prevalence in post-disaster #Fukushima residents 2015–2021

 

Abstract

This study aimed to investigate the prevalence of heart failure (HF) among adults aged ≥ 40 years using health checkup and medical claim data in Fukushima from 2015 to 2021. Joinpoint regression and age-period-cohort analyses were conducted to estimate temporal trends. Age-standardized prevalence and hospital admission rates for HF were 37.0 and 7.4/1000 and 25.9 and 5.3/1000 for men and women, respectively. The prevalence was significantly higher in the coastal area and evacuation zone designated after the 2011 disaster compared to the prefecture overall. In men, the prevalence increased continuously, with an average annual percentage change (AAPC) ranging from 0.72% (evacuation zone) to 1.15% (mountainous area) (P < 0.05). In total residents, the AAPC was significant only in the mountainous areas (0.78%, P = 0.021). Age-period-cohort analysis showed a net drift of 2.50% (95% CI 1.88–3.13%) in men and 0.76% (95% CI − 0.17–1.70%) in women. Cohort rate ratios increased significantly in men born between 1925 and 1975, while in women, they decreased for those born between 1925 and 1960 but increased for those born between 1960 and 1970. The prevalence of HF varied across post-disaster areas of Fukushima. Given that pathological changes and modifiable risk factors for HF accumulate gradually, continuous monitoring among middle-aged adults is essential to enable timely prevention and targeted intervention.

Source: 

Link: https://www.nature.com/articles/s41598-026-36032-0

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Humoral #immunity after #LP81 monovalent #vaccines against a broad range of #SARS-CoV-2 #variants including #XEC, LP.8.1, NB.1.8.1, #XFG, and #BA32

 

{Excerpt}

In the spring of 2025, multiple SARS-CoV-2 Omicron JN.1 subvariants were circulating, with LP.8.1 among the major variants. Pharmaceutical companies, such as Pfizer–BioNTech, Moderna, and Novavax–Takeda, adopted monovalent LP.8.1 for their 2025–26 season vaccines, following recommendations issued by WHO in May, 2025. As of November, 2025, SARS-CoV-2 variants including LP.8.1, XEC, NB.1.8.1, and XFG—all designated as variants under monitoring—were circulating. In terms of the spike gene, these variants, as well as LP.8.1, are derived from JN.1. Moreover, BA.3.2, a BA.3 descendant bearing multiple mutations in its spike gene, has potentially been spreading and exhibiting robust immune evasion. In Japan, the roll-out of the LP.8.1-based vaccination has progressed since the end of September, 2025. We previously reported the humoral immunity induced by the XBB.1.5-based monovalent vaccine in 2023,6 and the JN.1-based monovalent vaccine in 2024 in the Japanese population. We investigated the efficiency of humoral immunity induced by two LP.8.1-based vaccines, the mRNA vaccine from Pfizer–BioNTech and the recombinant protein-based vaccine from Novavax–Takeda, in Japan. Of note, the Novavax SARS-CoV-2 vaccine strain was updated to LP.8.1 only in Japan in 2025, whereas the formulation remains unchanged from JN.1 globally outside of Japan.

(...)

Source: 

Link: https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(25)00772-8/fulltext?rss=yes

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#Influenza PA #Substitutions and Genetic Diversity of #H1N1pdm09, #H3N2, and B/Victoria Viruses in #Japan During the 2023–2024 Season

 

Abstract

We characterized influenza A(H1N1)pdm09, A(H3N2), and B/Victoria viruses circulating in Japan during 2023–2024, focusing on lineage placement relative to WHO-recommended vaccine strains and on baloxavir resistance (PA/I38T substitutions). We enrolled 210 outpatients with influenza-like illness across eight clinics in six prefectures (October 2023–September 2024). Of these, 209 had an analyzable pre-treatment respiratory specimen for RT-PCR; hemagglutinin (HA) and neuraminidase (NA) genes were sequenced by next-generation sequencing (NGS). PA/I38T substitutions that confer baloxavir resistance were assessed by cycling-probe RT-PCR, Sanger sequencing, and NGS. HA phylogenies were constructed with global datasets and WHO vaccine reference strains. Of 209 pre-treatment specimens, 181 were influenza-positive (A(H1N1)pdm09 44.2%, A(H3N2) 37.6%, B/Victoria 18.2%); 51 follow-up specimens were collected ≈4–5 days after baloxavir or neuraminidase inhibitor therapy. HA phylogeny placed A(H1N1)pdm09 in clades 5a.2a/5a.2a.1 with predominance of subclade D.2. A(H3N2) clustered exclusively in clade 2a.3a.1 (J lineage, mostly J.1), indicating a mismatch with the season’s A/Darwin/9/2021 vaccine component and supporting the subsequent J-lineage update. All B/Victoria genomes fell within V1A.3a.2 on a C.5 backbone (C.5.1 and C.5.7). No PA/I38T variant was detected in any pre-treatment specimen. Post-baloxavir, PA/I38T emerged in one A(H3N2) case (confirmed by all three methods) and in one B/Victoria case detected by NGS only (minority variant in a low-load sample). NA genes showed no substitutions associated with reduced susceptibility to laninamivir (e.g., E119A, G147E). During 2023–2024, A(H1N1)pdm09 and B/Victoria remained genetically aligned with their vaccine components, whereas A(H3N2) shifted to the J lineage, consistent with the 2024–2025 vaccine update. Although pre-treatment PA/I38T was absent, low-frequency on-therapy selection was observed, including a rare PA/I38T in influenza B/Victoria detected by NGS, suggesting the value of deep sequencing when viral loads are low. These integrated genomic–clinical data support vaccine strain realignment for H3N2 and continued monitoring of baloxavir resistance in outpatient care.

Source: 

Link: https://www.mdpi.com/1999-4915/18/1/13

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Characterization of #H5N1 high pathogenicity avian #influenza virus belonging to clade 2.3.4.4b isolated from Ezo red #fox in #Japan in a mouse model

 

ABSTRACT

H5N1 high pathogenicity avian influenza virus (HPAIV) has spread in wild birds and poultry worldwide. H5N1 HPAIV belonging to the currently predominant clade 2.3.4.4b has infected not only birds but also mammals (wild and domestic animals), with several human infections also being reported, raising concerns for public health. In 2022, a clade 2.3.4.4b H5N1 HPAIV strain, A/Ezo red fox/Hokkaido/1/2022 (H5N1; Fox/Hok/1/22), was isolated from an Ezo red fox (Vulpes vulpes schrencki) in Hokkaido, Japan; this was the first reported case of clade 2.3.4.4b H5N1 HPAIV isolation from a mammalian species in Japan. Several amino acid substitutions in the PB2 protein play an important role in the adaptation of avian influenza viruses to mammals, but Fox/Hok/1/22 PB2 does not have any of these well-known mammalian-adapting PB2 substitutions. Here, we investigated the biological properties of Fox/Hok/1/22 in a mouse model and found that this virus was highly virulent in mice and replicated well in multiple organs, including the lungs and brain. We then examined whether viruses isolated from these organs acquired known mammalian-adapting PB2 amino acid substitutions, such as PB2 E627K. Deep sequencing analysis of viral RNA from mouse brain and lungs revealed that virus with PB2-627E was predominant in three of four mice, whereas the PB2-627K substitution was predominant in one mouse. These results indicate that Fox/Hok/1/22 is highly virulent in mice despite lacking known PB2 substitutions involved in mammalian adaptation.

IMPORTANCE

The H5N1 avian influenza virus has caused severe disease in birds worldwide and is now spreading to mammals, including humans. In 2022, this virus was detected for the first time in an Ezo red fox in Japan. To understand its potential impact on mammals, we studied this virus in mice and found that it caused severe illness, spreading to multiple organs, including the lungs and brain. Surprisingly, despite lacking genetic mutations typically associated with mammalian adaptation, the virus was highly virulent in mice. This finding suggests that the H5N1 virus may pose a greater threat to mammals, including humans, than previously thought. Given their continued spread among wild and domestic animals, our findings underscore the urgent need to monitor how recent H5N1 viruses behave in mammals.

Source: 

Link: https://journals.asm.org/doi/10.1128/spectrum.01097-25

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#Japan - #Influenza A #H5N1 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification

 

{By Norbert Kenntner, Berlin - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=1062838}

A wild Northern Goshawk in Hokkaido Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6909

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#Japan - High pathogenicity avian #influenza viruses (#poultry) (Inf. with) - Immediate notification

{ob1-Shiraoi-Town} On 21 October 2025, a Livestock Hygiene Service Centre (LHSC) in Hokkaido Prefecture received a notification from a domestic layer farm regarding an increase in bird mortality. Samples were collected from birds on the farm by LHSC officers and tested positive for influenza A virus using a viral antigen rapid test. On 22 October, the LHSC conducted RT-PCR and rRT-PCR tests and confirmed that the virus is of high pathogenicity. Movement and shipment restriction have been imposed on farms within a radius of 3 km and 10 km of the affected farm, respectively. Stamping-out and relevant control measures, including disinfection, are ongoing. The National Institute of Animal Health (NIAH) is sequencing the virus genome and will identify the subtype.

Source: WOAH, https://wahis.woah.org/#/in-review/6911

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First Isolation and Characterization of #LiaoNing Virus from #Aedes Vexans #Mosquitoes in #Hokkaido, #Japan, in 2022

Abstract

Background: 

The Liao ning virus (LNV), belonging to the genus Seadornavirus within the family Sedoreoviridae, is a mosquito-borne virus. It was originally isolated from Aedes dorsalis mosquitoes in China. The original LNV strain, LNVS-NE97-31, was reported to infect several mammalian cell lines and cause hemorrhagic symptoms in mice. Subsequently, another LNV strain, LNV NSW B115745, was isolated from Australian mosquitoes; it was reported to exhibit insect-specific infection.

Materials and Methods: 

Virus isolation was performed on mosquitoes collected in northern Hokkaido, Japan, in 2022. The isolated virus was subjected to genomic and growth kinetics analyses.

Results: 

A LNV strain was isolated from Aedes vexans mosquitoes. Genomic sequencing and phylogenetic analysis revealed the new strain as 22WN03, and it formed a robust clade with the original Chinese strain, LNVS-NE97-31. Growth kinetics analysis did not reveal any mammalian or avian cell line susceptible to infection by the strain 22WN03.

Conclusion: 

Overall, the results suggested that the strain 22WN03 has insect-specific infection characteristics, similar to as the Australian strain. Taken together, our findings could expand our knowledge of not only the diversity and geographical distribution of seadornaviruses in Asia but also the ecology of LNV.

Source: Vector-Borne and Zoonotic Diseases, https://www.liebertpub.com/doi/abs/10.1177/15303667251364143

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#Transmission Dynamics of Highly Pathogenic Avian #Influenza #H5N1 and #H5N6 Viruses in Wild #Birds, South #Korea, 2023–2024

Abstract

We analyzed 15 cases of highly pathogenic avian influenza (HPAI) clade 2.3.4.4b virus infections detected in wild birds in South Korea during September 2023–March 2024. We isolated and sequenced 8 H5N1 and 7 H5N6 viruses. We investigated spatiotemporal transmission dynamics by using a Bayesian discrete trait phylodynamic model that incorporated geographic and host species information. Our source–sink dynamics support introductions of H5N1 viruses from northern Japan to South Korea and subsequent spread through multiple regions in South Korea. The H5N6 viruses were most likely introduced into southwestern South Korea and spread northeastward. Wild waterfowl, especially wild ducks, played a key role in transmission of both H5N1 and H5N6 viruses. Our data showed multiple introductions and extensive spread of HPAI clade 2.3.4.4b viruses and bidirectional transmission between Japan and South Korea. Our results highlight the value of enhanced active surveillance for monitoring HPAI viruses, which can provide insight into preventing future outbreaks.

Source: US Centers for Disease Control and Prevention, https://wwwnc.cdc.gov/eid/article/31/8/25-0373_article

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In vitro and in vivo characterization of a #bat #merbecovirus with #ACE2- and #DPP4-independent cell entry

ABSTRACT

Betacoronaviruses, which have caused three human outbreaks within the last two decades, are thought to originate from bats, raising the concern that bat coronaviruses could cause a novel human outbreak in the future. To determine whether the bat merbecovirus EjCoV-3 strain, previously detected in Eptesicus japonensis in Japan, has the potential to infect humans, we analyzed its cellular entry mechanism. Cellular entry of EjCoV-3 via the spike protein requires protease treatment and is mediated by an unknown receptor, other than DPP4 or ACE2. We generated cultivable recombinant EjCoV-3 using bacterial artificial chromosome-based reverse genetics and found that it efficiently replicated in human respiratory and intestinal cell cultures as well as nasal ciliated epithelium in hamsters. These findings suggest that bat merbecovirus with ACE2- and DPP4-independent cell entry has the potential to cause human infections, highlighting the importance of extensive bat surveillance for pandemic preparedness.

IMPORTANCE

Betacoronaviruses, including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-2, have caused three significant outbreaks in the past two decades and are believed to have originated from bats. To investigate the potential for future outbreaks, we generated a Japanese bat-derived MERS-related coronavirus, designated EjCoV-3, using reverse genetics. Our results showed that EjCoV-3 does not utilize ACE2 and DPP4, cell entry receptors for SARS-CoV and MERS-CoV, as a means of infection. However, we found that EjCoV-3 is the first bat merbecovirus capable of efficiently replicating in human respiratory cells and the respiratory tract of hamsters. These findings provide new insight into the potential for MERS-related coronaviruses that do not use ACE2 and DPP4 to infect the human respiratory tract, highlighting the importance of preparedness for outbreaks caused by these viruses.

Source: Journal of Virology, https://journals.asm.org/doi/full/10.1128/jvi.00727-25?af=R

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#Japan - #Influenza A #H5N1 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification [FINAL]

 Sea Otters in Hokkaido Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6551

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#Japan - #Influenza A #H5N2 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification

 A wild Peregrine falcon in Kagoshima Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6545

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Highly Pathogenic Avian #Influenza A(#H5N1) #Outbreak in Endangered #Cranes, Izumi Plain, #Japan, 2022–23

Abstract

During the 2022–23 winter season, >1,500 endangered cranes, including hooded crane (Grus monacha) and white-naped crane (Grus vipio), were found debilitated or dead in the Izumi Plain, Japan. Most of the cranes, particularly those collected in November, were infected with highly pathogenic avian influenza (HPAI) H5N1 viruses; virus shedding was higher from the trachea than from the cloaca. The isolation rate from the cranes’ roost water was not markedly higher than that of previous seasons, suggesting that the viruses might be more effectively transmitted among cranes via the respiratory route than through feces. Most wild bird–derived H5N1 isolates were phylogenetically distinct from viruses isolated on nearby chicken farms, indicating limited relationship between the wild bird and chicken isolates. Serologic analyses suggested that herd immunity had little effect on outbreak subsidence. This study deepens our understanding of the circumstances surrounding the unexpected HPAI outbreaks among these endangered cranes.

Source: US Centers for Disease Control and Prevention, https://wwwnc.cdc.gov/eid/article/31/5/24-1410_article

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#Japan - Equine #influenza virus (Inf. with) - Immediate notification

 <Outbreaks 1-3> In early April, Livestock Hygiene Service Centres (LHSCs) in Kumamoto Prefecture received notifications from farmers with animals presenting clinical signs and collected samples. On 8 April, the LHSCs confirmed positive for Equine Influenza by RT-PCR. Genotyping is currently underway.

Source: WOAH, https://wahis.woah.org/#/in-review/6420

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#Influenza #H1N1pdm09 Virus with Reduced Susceptibility to #Baloxavir, #Japan, 2024

Abstract

Influenza A(H1N1)pdm09 virus carrying an I38N substitution was detected in an untreated teenager in Japan. The I38N mutant virus exhibited reduced susceptibility to baloxavir but remained susceptible to neuraminidase inhibitors and showed reduced growth capability. Monitoring antiviral drug susceptibility of influenza viruses is necessary to aid public health planning and clinical recommendations.

Source: US Centers for Disease Control and Prevention, https://wwwnc.cdc.gov/eid/article/31/5/24-1123_article

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#Japan - #Influenza A #H5 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification

 Three wild Hooded Cranes in Izumi Region, Kagoshima city.

Source: WOAH, https://wahis.woah.org/#/in-review/6239

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Detection of #antibodies against #H5 subtype highly pathogenic avian #influenza viruses in multiple #raccoons in Tokachi District, #Hokkaido, #Japan, from 2022 to 2023

Abstract

In recent years, infection cases of H5 subtype highly pathogenic avian influenza viruses (HPAIVs) in wild mammals have increased globally. To obtain recent epidemiological information regarding influenza A virus (IAV) infection in raccoons (Procyon lotor), the prevalence of anti-IAV antibodies in sera was analyzed among raccoons captured in Tokachi District, Hokkaido, Japan, from 2019 to 2023. Screening of serum samples using enzyme-linked immunosorbent assay and agar gel precipitation test detected anti-IAV antibodies in 5 of 114 (4.4 %) raccoons. All positive sera were from raccoons captured from 2022 to 2023. The hemagglutination inhibition test revealed that all five serum samples contained anti-H5 subtype HPAIV antibodies, and one also contained anti-H1 subtype antibodies. The neuraminidase inhibition test revealed that all five sera contained anti-N1 subtype antibodies, and one also contained anti-N8 subtype antibodies. In the virus neutralization test, these five sera showed stronger neutralization activity against the H5 subtype clade 2.3.4.4b HPAIV strain recently circulating worldwide compared to the old H5 HPAIV strain isolated in Japan in 2007. These findings suggested that raccoons could be involved in the circulation of H5 HPAIVs in nature.

Source: Virus Research, https://www.sciencedirect.com/science/article/pii/S0168170224002089?via%3Dihub

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Long-term immune responses induced by low-dose #infection with high pathogenicity avian #influenza viruses can protect #mallards from reinfection with a heterologous strain

Abstract

Migratory water birds are considered to be carriers of high pathogenicity avian influenza viruses (HPAIVs). In Japan, mallards are often observed during winter, and HPAIV-infected mallards often shed viruses asymptomatically. In this study, we focused on mallards as potential carriers of HPAIVs and investigated whether individual wild mallards are repeatedly infected with HPAIVs and act as HPAIV carriers multiple times within a season. Mallards were experimentally infected with H5N1 and H5N8 HPAIVs that were isolated recently in Japan and phylogenetically belong to different hemagglutinin groups (G2a, G2b, and G2d). All of these strains are more infectious to mallards than to chickens, and the infected mallards shed enough virus to infect others, regardless of whether they exhibited clinical signs. Serum antibodies to the homologous antigen, induced by a single infection with a low virus dose (10 times the 50% mallard infectious dose), were maintained at detectable levels for 84 days. Immunity at 84 days post-inoculation fully protected the mallards from a challenge with the homologous strain, as demonstrated by a lack of viral shedding, and antibody levels did not increase significantly in most of these birds. Protection against heterologous challenge was also observed despite undetectable levels of antibodies to the challenge strain. Our findings suggest that repeated infections with homologous and heterologous HPAIV strains do not occur frequently in individual wild mallards within a season, particularly at low viral doses, and the frequency with which they act as carriers may be limited.

Source: Archives of Virology, https://link.springer.com/article/10.1007/s00705-024-06209-x

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Acute #Encephalopathy Associated with #Human #Adenovirus Type 14 Infection in 7-Year-Old Girl, #Japan

Abstract

Only 2 cases of human adenovirus type 14 (HAdV-14) have been reported in Japan since 1980. We report a 7-year-old girl with acute encephalopathy associated with HAdV-14 infection genetically similar to strains from the United States. The patient had not had contact with international travelers. HAdV-14 surveillance should be strengthened in Japan.

Source: Emerging Infectious Diseases Journal, https://wwwnc.cdc.gov/eid/article/31/2/24-1168_article

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