The first reported case of #candidemia caused by the novel #Candida tropicalis diploid sequence type 1515

Abstract

Introduction: 

Since the dawn of the new millennium, Candida species have been increasingly implicated as a cause of both healthcare-associated as well as opportunistic yeast infections, due to the widespread use of indwelling medical devices, total parenteral nutrition, systemic corticosteroids, cytotoxic chemotherapy, and broad-spectrum antibiotics. Candida tropicalis is a pathogenic Candida species associated with considerable morbidity, mortality, and drug resistance issues on a global scale.

Methodology: 

We report a case of a 43-year-old man who was admitted to our hospital for further management of severe coronavirus disease 2019 (COVID-19) pneumonia. During his stay in the ward, he received systemic corticosteroids for a total duration of 32 days. A broad-spectrum antibiotic (piperacillin-tazobactam) was also given due to copious amounts of tracheostomy secretions.

Results: 

The patient’s fever recurred following an afebrile interval of 11 days, and C. tropicalis was cultured from his blood. The yeast was highly resistant to fluconazole and voriconazole but remained susceptible to echinocandins. Unfortunately, the patient was unable to receive any echinocandin and eventually succumbed to candidemia.

Conclusions: 

Multilocus sequence typing was used to characterize C. tropicalis as a novel diploid sequence type (i.e., 1515) that has not been previously reported.

Source: Journal of Infection in Developing Countries, https://www.jidc.org/index.php/journal/article/view/39863954

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Fire-Swept Hills, Tom Thomson (1915)

 

Public Domain.

Source: WikiArt, https://www.wikiart.org/en/tom-thomson/fire-swept-hills-1915

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#Hemagglutinin with a #polybasic #cleavage site confers high #virulence on #H7N9 avian #influenza viruses

Abstract

H7N9 avian influenza virus (AIV) first emerged in February 2013 in China, and early isolates were all low pathogenic (LP). After circulation for a few years in live poultry markets of China, LP H7N9 AIVs evolved into a highly pathogenic (HP) form in late 2016. Deduced amino acid sequence analysis of hemagglutinin (HA) gene revealed that all HP H7N9 AIVs have obtained four-amino-acid insertion at position 339-342 (H7 numbering), making the cleavage site from a monobasic motif (LP AIVs) to a polybasic form (HP AIVs). Notably, the polybasic cleavage site motifs are diversified, of which PEVPKRKRTAR↓GLF motif is prevalent. To elucidate the reasons accounting for its dominance, recombinant H7N9 virus carrying PEVPKRKRTAR↓GLF (rJT157-2) motif was generated based on LP H7N9 virus A/chicken/Eastern China/JT157/2016 (JT157). Besides, another two viruses containing PEVPKGKRTAR↓GLF (rJT157-1) and PEIPKRKRTAR↓GLF (rJT157-3) cleavage site motifs were also constructed as comparisons. We found that rJT157-2 showed better biological characterizations in vitro including replication kinetics, plaque size, thermal and acid stability. In addition, animal experiments demonstrated that rJT157-2 was more pathogenic to both chickens and mice with higher virus titers and induced more severe changes in the lungs. These results suggested that HP H7N9 viruses carrying PEVPKRKRTAR↓GLF motif in the HA cleavage site were most likely adaptive mutants during the evolution of H7N9 AIVs.

Source: Poultry Science, https://www.sciencedirect.com/science/article/pii/S0032579125000690?via%3Dihub

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#Remdesivir and #Obeldesivir Retain Potent #Antiviral Activity Against #SARS-CoV-2 #Omicron Variants

Abstract

As new SARS-CoV-2 variants continue to emerge, it is important to evaluate the potency of antiviral drugs to support their continued use. Remdesivir (RDV; VEKLURY®) an approved antiviral treatment for COVID-19, and obeldesivir (ODV) are inhibitors of the SARS-CoV-2 RNA-dependent RNA polymerase Nsp12. Here we show these two compounds retain antiviral activity against the Omicron variants BA.2.86, BF.7, BQ.1, CH.1.1, EG.1.2, EG.5.1, EG.5.1.4, FL.22, HK.3, HV.1, JN.1, JN.1.7, JN.1.18, KP.2, KP.3, LB.1, XBB.1.5, XBB.1.5.72, XBB.1.16, XBB.2.3.2, XBC.1.6, and XBF when compared with reference strains. Genomic analysis identified 29 Nsp12 polymorphisms in these and previous Omicron variants. Phenotypic analysis of these polymorphisms confirmed no impact on the antiviral activity of RDV or ODV and suggests Omicron variants containing these Nsp12 polymorphisms remain susceptible to both compounds. These data support the continued use of RDV in the context of circulating SARS-CoV-2 variants and the development of ODV as an antiviral therapeutic.

Source: Viruses, https://www.mdpi.com/1999-4915/17/2/168

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#Detection of low pre-existing #humoral #immunity against #influenza virus #H5N1 clade 2.3.4.4b in unexposed individuals

Abstract

The repeated spill-over of Influenza A virus H5N1 clade 2.3.4.4b from cattle to humans highlights the risk of a human H5N1 pandemic. Given the impact of pre-existing immunity on the course and severity of viral infections, we assessed in detail the humoral immunity against the H5N1 A/Texas/37/2024 isolate in H5N1-naive individuals. To this end, we performed complementary binding and neutralization assays on 66 subjects and ranked activities among a panel of 76 influenza A virus isolates. We detected low but distinct cross-neutralizing titers against A/Texas/37/2024 with a 3.9 to 15.6-fold reduction compared to selected H1N1 or H3N2 strains. Moreover, by cloning and evaluating 136 monoclonal antibodies from single memory B cells, we identified potent A/Texas/37/2024-neutralizing monoclonal antibodies in five out of six investigated individuals. These antibodies predominantly utilize VH1-69 gene segments, cross-neutralize H1, and compete with antibodies targeting the HA stem. Our findings demonstrate partial pre-existing humoral immunity to A/Texas/37/2024 in H5N1-naive individuals.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.01.22.634277v1

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Novel introductions of #human-origin #H3N2 #influenza viruses in #swine, #Chile

Abstract

Influenza A virus (IAV) continuously threatens animal and public health globally, with swine serving as a crucial reservoir for viral reassortment and evolution. In Chile, H1N2 and H3N2 subtypes were introduced in the swine population before the H1N1 2009 pandemic, and the H1N1 was introduced from the H1N1pdm09 by successive reverse zoonotic events. Here, we report two novel introductions of IAV H3N2 human-origin in Chilean swine during 2023. Our study reveals a closer relationship between recent human seasonal H3N2 and novel swine strains. Interestingly, one strain maintains all the genes from the original human virus, but the other strain is already a reassortment of human H3N2 and an H1N2 previously observed on the farm. Observing global IAV sequences, a similar pattern was identified in the USA confirming the reverse zoonotic potential of current seasonal human H3N2 strains. These results highlight the importance of ongoing surveillance and reinforcing biosecurity in swine farms. These findings raise questions about their potential impact on viral dynamics in the swine population and public health, underscoring the need for further investigation into the origin and evolutionary dynamics of this emerging swine H3N2 reassortant virus.

Source: Frontiers in Veterinary Medicine, https://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets.2024.1505497/full

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Phylogeography and biological characterization of #H12N2 virus isolated from whooper #swan in Central #China

Abstract

Wild birds and waterfowl serve as the natural reservoirs of avian influenza viruses (AIVs). When AIVs originating from wild birds cross species barriers to infect mammals or humans, they pose a significant threat to public health. The H12 subtype of AIVs primarily circulates in wild birds, with relatively few isolates reported worldwide, and the evolutionary and biological characteristics of H12 subtype AIVs remain largely unknown. In this study, we analyzed the spatiotemporal distribution of H12 subtype AIVs worldwide and conducted a comprehensive investigation into the evolutionary and biological characteristics of an H12N2 virus isolated from a whooper swan in Central China. Phylogenetic analysis revealed that the H12N2 isolate belongs to the Eurasian lineage, with its HA gene likely originating from a duck-derived H12N5 virus and its NA gene potentially derived from an H9N2 virus, indicating that it is a complex reassorted virus. Animal experiments in domestic ducks and chickens demonstrated that the virus replicates at low levels in the respiratory tract of poultry and exhibits moderate horizontal transmission in ducks. However, it is capable of efficient horizontal transmission in chickens. Mouse infection experiments revealed that the virus could be detected in the nasal turbinates and lungs of mice, indicating that the H12N2 virus can infect mice without prior adaptation. In vitro studies revealed that the virus replicates efficiently in MDCK cells, with significantly higher titers than those in DF1 cells. These findings, combined with the mouse infection results, suggest that the H12N2 virus poses a potential risk of mammalian infection. This study provides valuable insights regarding the characteristics of the H12N2 virus and highlights the importance of ongoing surveillance and risk assessment of AIVs originating from wild birds.

Source: Frontiers in Microbiology, https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2024.1536876/full

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#USA, Monitoring for Avian #Influenza A(#H5) Virus In #Wastewater (Jan 12-18 '25)

 {Excerpt}

Time Period: January 12 - January 18, 2025

-- H5 Detection: 35 sites (10.4%)

-- No Detection: 301 sites (89.6%)

-- No samples in last week: 62 sites

(...)

Source: US Centers for Disease Control and Prevention, https://www.cdc.gov/bird-flu/h5-monitoring/index.html

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

 Unspecified domestic birds in Leiria Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6214

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#Antiviral activity of #tecovirimat against #monkeypox virus clades 1a, 1b, 2a, and 2b

{Excerpt}

The zoonotic Orthopoxvirus monkeypox virus includes two main clades (ie, 1 and 2) relevant to human transmission.1 Two major outbreaks of monkeypox virus have occurred since 2022,1–3 and were declared public health emergencies of international concern by WHO in July, 2022, and August, 2024. The first outbreak was caused by a clade 2b strain that quickly spread worldwide, resulting in approximately 100 000 cases and 200 deaths.3 In the second outbreak, the novel clade 1b emerged.4 As of December, 2024, this upsurge has resulted in more than 55 000 reported or suspected cases and approximately 1000 deaths in DR Congo and neighbouring countries, including Burundi, Rwanda, Uganda, and Angola.4 A few imported clade 1b cases have also been reported in the UK, Sweden, Germany, Belgium, France, the USA, Canada, and Thailand.5 Prevention measures include patient isolation and care as well as vaccines.

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Source: Lancet Infectious Diseases, https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(25)00014-3/fulltext?rss=yes

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Characterization of novel highly pathogenic avian #influenza A(#H5N6) clade 2.3.4.4b virus in wild #birds, East #China, 2024

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Dear Editor,

The highly pathogenic avian influenza viruses (HPAIVs) are important epizootic and zoonotic pathogens that cause significant economic losses to the poultry industry and pose a serious risk to veterinary and public health. Wild birds have been recognized as the primary reservoirs for influenza A virus, and some species show little sign of clinical disease or even can be asymptomatic during long distance carriers of the virus (Lycett et al., 2019). Since it was first discovered in 1959, the H5Nx HPAIVs have spread globally and cause outbreaks in wild birds, poultry and sporadic human and other mammalian infections (Lycett et al., 2019). Due to the reassortant events of diverse strains facilitated by migratory waterfowl, the clade 2.3.4.4 of H5Nx viruses acquiring neuraminidase (NA) gene from other low pathogenicity avian influenza viruses (LPAIVs) emerged in 2014 and gradually became the dominant sub-clade (Lee et al., 2017). The genetic diversity of clade 2.3.4.4 of H5Nx hemagglutinin (HA) has further evolved into eight subclades (2.3.4.4a to 2.3.4.4h) according to a unified nomenclature (Graziosi et al., 2024). H5N6 of clades 2.3.4.4d-h were predominantly identified in China from 2014 to early 2020 until the occurrence of a novel H5N6 derived the clade 2.3.4.4b HA gene of H5N8 in December 2020 (Gu et al., 2022). Subsequently, the preponderant clade of the H5N6 subtype HPAIV in China switched into 2.3.4.4b. Recently, novel H5N6 HPAIVs containing HA gene from clade 2.3.4.4b H5N1 virus entered R. O. Korea, with disease outbreaks in poultry and wild bird mortality events (Cho et al., 2024; Heo et al., 2024).

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Source: Virologica Sinica, https://www.sciencedirect.com/science/article/pii/S1995820X25000021?via%3Dihub

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#Receptor #binding, #structure, and #tissue #tropism of #cattle-infecting #H5N1 avian #influenza virus #hemagglutinin

Summary

The ongoing circulation of highly pathogenic avian influenza (HPAI) A (H5N1) viruses, particularly clade 2.3.4.4b strains, poses a significant threat to animal and public health. Recent outbreaks in cattle highlight concerns about cross-species transmission and zoonotic spillover. Here, we found that the hemagglutinin (HA) protein from a cattle-infecting H5N1 virus has acquired slight binding to human-like α2-6-linked receptors while still exhibiting a strong preference for avian-like α2-3-linked sialic acid receptors. Immunohistochemical staining revealed HA binding to bovine pulmonary and mammary tissues, aligning with clinical observations. HA also binds effectively to human conjunctival, tracheal, and mammary tissues, indicating a risk for human transmission, notably in cases of conjunctivitis. High-resolution cryo-electron microscopy (cryo-EM) structures of this H5 HA in complex with either α2-3 or α2-6 receptors elucidate the molecular mechanisms underlying its receptor-binding properties. These findings provide critical insights into the tropism and transmission potential of this emerging pathogen.

Source: Cell, https://www.cell.com/cell/abstract/S0092-8674(25)00048-0

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The sweet side of #H5N1 #influenza virus #infection

Summary

H5Nx viruses remain a threat to human health. Over the past few years, the H5Nx clade 2.3.4.4b has rapidly spread to 6 continents, leading to massive avian and mammalian host deaths. In late March 2024, H5N1 was first identified in lactating dairy cows in the United States and has spread to 16 states, affected hundreds of herds, and caused over 50 known human infections. In this review, we discuss the origins of 2.3.4.4b H5N1 viruses and how they are evolving to better infect mammals, with an emphasis on receptor-binding characteristics. Understanding changes in receptor binding and mutations in the viral genome that allow for sustained spread in mammals can inform public health measures and prevent future influenza virus epidemics and pandemics.

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Source: PLoS Pathogens, https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1012847

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Exotic and #Zoological #Birds Resident and Imported into #Nigeria harbour Highly Pathogenic Avian #Influenza Virus: #Threat to #Poultry Production, Food security and Public Health.

Abstract

Influenza is a major infectious disease challenge affecting animal and human health globally, and wild birds are historically the primary reservoirs of all the known Influenza A virus subtypes. Here, we detected the Highly Pathogenic Avian Influenza (HPAI) virus in exotic and aquatic birds in three different locations in Nigeria. On the 8th of February 2021, exotic birds: Yellow Golden Pheasant (Chrysolophus pictus), Sultan chicken (Gallus gallus domesticus), Lakenvelder chicken (Gallus gallus domesticus), and Common pheasant (Phasianus calchicus), imported from Libya and transported across the Niger Republic border to Nigeria, were presented to the National Veterinary Research Institute, Vom, for screening. Also, a family in Lagos State bought some exotic aquatic birds from a live bird market in Sokoto State, Nigeria, where sudden death was recorded with the birds showing few clinical signs. Similarly, the sudden death of some aquatic birds was reported in Mandela Parks and Gardens in Asaba, Delta State, few weeks after some captured wild birds were introduced to the Park and Gardens. Oropharyngeal, cloacal, and tissue samples were all collected from the reported cases. Total viral nucleic acid was extracted and screened for Influenza A viruses using real-time RT-PCR. The HPAI viruses H5N1 and H5N8 were detected in the imported aquatic (geese and ducks) and exotic (yellow golden pheasant) birds. The samples tested negative for low-pathogenic Avian Influenza Virus (H9N2) as well as other avian viruses, viz., Avian avulavirus-1 (Newcastle disease Virus) and infectious bronchitis virus. This highlights the role of these resident and imported exotic birds in the local transmission and spread of the HPAI virus to domestic poultry. The findings call for proper biosecurity and quarantine measures for exotic and wild birds to reduce the potential risk to animal and public health in Nigeria.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.01.22.634354v1

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#UK - High pathogenicity avian #influenza #H5N1 viruses (#poultry) (Inf. with) - Immediate notification, 3rd

A 1.4 million egg laying and rearing flock. Increased mortality and other clinical signs were reported. Samples taken tested positive for HPAI H5N1. England, Shropshire Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6209

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#UK - High pathogenicity avian #influenza #H5N1 viruses (#poultry) (Inf. with) - Immediate notification, 2nd

A 13,316 commercial turkey fattening unit. Increased mortality and other clinical signs were reported. Samples taken and tested positive for HPAI H5N1. England, East Riding of Yorkshire Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6206

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#UK - High pathogenicity avian #influenza #H5N1 viruses (#poultry) (Inf. with) - Immediate notification

A 240 free-range layer unit. Increased mortality and other clinical signs were reported. Samples taken and tested positive for HPAI H5N1. England, East Sussex Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6207

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Chronic Systemic #SARS-CoV-2 #Infection Without Respiratory Involvement in an Immunocompromised Patient

Abstract

In a patient on immunosuppressant treatment, SARS-CoV-2 RNA was documented in different extra-respiratory samples over several months in the absence of positive determinations in upper respiratory samples. Whole-genome sequencing of these samples showed the acquisition of different single-nucleotide polymorphisms over time, suggesting viral evolution and thus viral viability.

Source: Viruses, https://www.mdpi.com/1999-4915/17/2/147

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