•A rare hantavirus outbreak on MV Hondius in May 2026 caused 8 cases and 3 deaths.•Cruise ship confined spaces and HVAC systems facilitated aerosol transmission.•Jurisdictional disputes delayed critical medical evacuations.•Lack of isolation and diagnostics exposed cruise ship medical vulnerabilities.•Pathogen research and robust maritime emergency protocols are needed.
Human respiratory syncytial virus (RSV) remains a leading cause of lower respiratory tract illness (LRTI) in infants, young children, and the elderly. Although long-acting monoclonal antibodies, subunit, and messenger ribonucleic acid (mRNA) vaccines can protect vulnerable populations (infants < 6 months old and older adults) via passive and active immunization, respectively, a conspicuous protection gap remains for RSV-seronegative infants and young children aged 6 to 60 months, leaving this vulnerable pediatric cohort largely unprotected. For these RSV-seronegative pediatric populations, intranasal live-attenuated vaccines (LAVs) have emerged as promising formulations owing to the key advantage of lacking vaccine-associated enhanced respiratory disease (VAERD) following natural RSV infection in vaccine recipients. Furthermore, intranasal RSV LAVs can induce the full spectrum of protective immune responses against the virus systemically and locally, including neutralizing antibodies, secretory IgA (SIgA), and tissue-resident memory CD8+ T (TRM) cells. Despite the suboptimal Phase 3 efficacy of Sanofi's RSVt candidate (RSV/ΔNS2/Δ1313/I1314L), alternative RSV LAVs featuring the M2-2 gene deletions have shown enhanced efficacy in clinical studies, alongside emerging strategies designed to rationally augment the immunogenicity of RSV LAVs. Due to the sustained efforts over the past five decades on RSV LAVs, significant advances have been made both in the technology to generate RSV LAVs-most notably reverse genetics-and in our understanding of pivotal benchmarks, including attenuation design, evaluation criteria for attenuation and immune efficacy, as well as the stepwise strategy for clinical research in RSV-seronegative children. Concurrently, this review provides a comprehensive synthesis of these historical and ongoing efforts, while highlighting future directions to prevent RSV disease in RSV-seronegative pediatric populations.
The 2024 World Health Organization (WHO) Bacterial Priority Pathogens List (BPPL) updates the 2017 framework by expanding to 24 pathogens across 15 bacterial families, addressing the growing antimicrobial resistance (AMR) crisis, which was estimated to have caused 1.27 million deaths in 2019. The revised list introduces four new pathogen-antibiotic combinations—rifampicin-resistant Mycobacterium tuberculosis, macrolide-resistant Group A Streptococci, macrolide-resistant Streptococcus pneumoniae, and penicillin-resistant Group B Streptococci—while removing five, including clarithromycin-resistant Helicobacter pylori, reflecting evolving resistance patterns, regional disparities, and therapeutic advancements. Notably, third-generation cephalosporin-resistant Enterobacterales is now a standalone critical-priority pathogen due to its high burden in low- and middle-income countries. This review examines these updates, driven by complex resistance mechanisms, surveillance gaps, and the impact of coronavirus disease 2019 (COVID-19)-related antibiotic misuse. It highlights trends such as the dominance of Gram-negative bacteria, rising rates of community-acquired infections, and the urgent need for innovative therapies, including phage therapy, phenazine-based antimicrobials, and metal-based strategies. Enhanced global surveillance, equitable access to treatments, and collaborative efforts are critical to combating AMR effectively.
The World Health Organization has updated the Priority Pathogens List based on risk assessments of the world’s endemic pathogens, the majority of which are viruses. This assessment proposed to extend research and preparation to the entire families of Priority Pathogens, rather than just focusing on individual known high-risk pathogens. The 21 viruses on the Priority Pathogens List belong to 13 virus families. Viruses within the same family have similarities in genes, immunogens, immunity, and transmission, etc. A protective immunogen is an antigenic component that can induce a protective immune response in the immune system after the invasion of pathogenic microorganisms, and it always serves as the early focal point of vaccines and treatment method developments during an outbreak. Here, we summarized the protective immunogens of Priority Pathogens, found the common features of protective immunogens of viruses in the same family, and proposed that the development of vaccines and screening of neutralizing antibodies based on this clue may be applied to the prevention and control of the epidemics or even pandemics of these Priority Pathogens.
The ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has compromised the efficacy of many neutralizing antibodies. Receptor-mimicking antibodies, whose binding modes partially resemble those of angiotensin-converting enzyme 2 (ACE2), are of particular interest as they recognize functionally constrained regions of the receptor-binding domain (RBD). However, whether these antibodies retain activity against newly emerged SARS-CoV-2 variants remains unclear. In this study, two representative receptor-mimicking antibodies, VIR-7229 and S2K146, were evaluated alongside S2H13, another RBD-targeting antibody. VIR-7229 and S2K146 retained neutralizing activity better than S2H13, with VIR-7229 showing the greatest retention. VIR-7229 potently neutralized the Wuhan-Hu-1, BA.1, XBB.1.5, and BA.2.86 variants and exhibited reduced yet considerable neutralizing activity against KP.3.1.1, XEC, and XEC.25.1. Enzyme-linked immunosorbent assay (ELISA) and biolayer interferometry further demonstrated that VIR-7229 maintained strong binding to spike proteins from recent variants. Computational structural analysis suggested that mutations in these variants may weaken VIR-7229 binding to the RBD but do not fully disrupt the antibody-RBD interface. These findings indicate that VIR-7229 retains considerable neutralizing activity and robust spike recognition against recent SARS-CoV-2 variants, likely through recognition of a functional interface involved in ACE2 binding. This study supports further evaluation of receptor-mimicking antibodies and may inform the design of candidate immunogens against evolving SARS-CoV-2 variants.
Bangladesh has historically maintained a low-level human immunodeficiency virus (HIV) epidemic; however, recent surveillance indicates a shifting burden toward men who have sex with men (MSM). This study aimed to assess temporal trends and comparative HIV risk among key populations in Bangladesh. National HIV surveillance data from 2016 to 2025 were analyzed using univariate logistic and Poisson regression models. MSM showed a markedly higher risk (odds ratio [OR] = 5.89; 95% confidence interval [CI]: 5.05-6.90; P < 0.001) of HIV infection compared with people who inject drugs and a significantly higher incidence rate (log-incidence rate ratio [IRR] = 1.2, 95% CI: 1.1-1.3; P < 0.001). Temporal analysis revealed a steep increase in HIV risk among MSM, with odds rising from 2.20 in 2020 to 15.2 in 2025 relative to 2019. These findings indicate an emerging concentrated HIV epidemic among MSM in Bangladesh, underscoring the need for strengthened, context-specific prevention strategies, particularly considering known socio-structural barriers.
In May 2026, an outbreak of Andes virus (ANDV) infection aboard the expedition cruise ship MV Hondius resulted in 13 reported cases (12 confirmed and one probable) and three deaths. ANDV causes severe hantavirus cardiopulmonary syndrome (HCPS) and exhibits a documented, albeit limited, capacity for person-to-person transmission under prolonged close contact. Although the precise transmission route in this cluster remains undetermined, the available evidence is compatible with common-source exposure before or during embarkation, limited close-contact transmission on board, or a combination of both. Definitive attribution requires linked epidemiological and genomic data. The outbreak exposed deficiencies in early clinical recognition, diagnostic access, surveillance coordination, risk communication, and the ready availability of medical countermeasures. This perspective therefore has three interrelated objectives: (i) to identify priority research questions concerning ANDV and related hantaviruses that have emerged from the maritime cluster; (ii) to evaluate the current state of vaccine and antibody development and establish priorities for epitope-informed design; and (iii) to propose actionable biosafety and biosecurity measures for cruise operators, port health authorities, and reference laboratories. We argue that countermeasure strategies should prioritize neutralization-sensitive conformational and quaternary epitopes on the N-terminal envelope glycoprotein (Gn) and C-terminal envelope glycoprotein (Gc), while nucleocapsid protein epitopes are exploited for surveillance and serological diagnosis. Rather than signaling uncontrolled community spread, the outbreak reinforces the urgent case for integrated epidemiological, genomic, immunological, and operational preparedness against future threats posed by ANDV and related hantaviruses
Chikungunya virus (CHIKV) is a globally emerging arthropod-borne virus causing widespread febrile outbreaks, with its endemic regions showing extensive geographical overlap with human immunodeficiency virus (HIV). Approximately 71% of people living with HIV (PLWH) reside in CHIKV high-risk areas globally, while the clinical features and underlying immunological interplay of CHIKV-HIV co-infection have not been systematically synthesized. This review integrates current evidence on CHIKV host immune responses, alongside the epidemiological characteristics, clinical manifestations, and immunopathological mechanisms of CHIKV infection in PLWH, to deliver integrated clinical and immunological insights into co-infection. Available data indicate that PLWH on suppressive antiretroviral therapy (ART) generally present with milder CHIKV disease, with potential mechanisms involving HIV-induced immune system alterations and direct antiviral activity of ART. This review provides an evidence-based framework for clinical management and public health prevention strategies for this vulnerable population.
Monitoring viral evolutionary dynamics in regions with complex demographics is essential for understanding the adaptation and transmission patterns of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Yunnan Province, situated in Southwest China and characterized by significant cross-border population movement, offers a unique context for regional surveillance. A total of 1,011 respiratory samples collected between 2023 and 2025 were screened for SARS-CoV-2. Among these, 212 samples exhibiting a cycle threshold (Ct) value of less than 32 underwent whole-genome sequencing. Additionally, 47 publicly available genomes from the Global Initiative on Sharing All Influenza Data (GISAID) were incorporated into the phylogenetic analysis. Viral evolution, lineage dynamics, and mutational patterns were assessed using Nextstrain (v2.4.1). The potential immune escape characteristics of receptor-binding domain (RBD) mutations were examined using previously published deep mutational scanning datasets. The predominant circulating variants transitioned from clade 22D to clade 25B, primarily represented by the NB.1.8.1 lineage. Several recurrent spike mutations, including E484K, Y505H, and F456L, were detected in the dominant clades; these mutations have been associated with immune escape-related phenotypes. Phenotypic modeling indicated that these mutations may lead to increased immune escape scores, potentially compromising the efficacy of antibody-based interventions. Phylogenetic analysis revealed distinct lineage replacement patterns throughout the study period. The unique regional context may contribute to the complexity of SARS-CoV-2 circulation dynamics and lineage diversity within the region. Ongoing regional genomic surveillance, alongside phylogenetic and phenotypic analyses, is essential for identifying emerging variants with potential immune-evasion characteristics.
Chikungunya fever, caused by the mosquito-borne chikungunya virus (CHIKV), poses a significant global health burden, with an estimated 16.9 million infections annually. Although CHIKV infection induces neutralizing antibody responses, data on their long-term persistence remain limited. In July 2017, an imported outbreak caused by the CHIKV East/Central/South African genotype occurred in Zhejiang Province, China. To assess the longevity of neutralizing antibodies, we conducted a cross-sectional follow-up study in August 2025, approximately eight years after infection. Two laboratory-confirmed patients from the outbreak were enrolled, and serum samples were collected. Serum neutralizing antibodies were measured using both pseudovirus and authentic CHIKV neutralization assays. Remarkably robust and sustained responses were observed in both patients. The pseudovirus neutralization titers were 225,677 and 134,460, respectively, and authentic virus neutralization titers were 9,133 and 4,951, respectively—which substantially exceeded the established protective threshold of 150. As no subsequent CHIKV outbreaks were documented in this non-endemic region, these high neutralizing antibody titers indicate that durable immunity may be derived from a single infection rather than repeated boosting. These findings suggest that natural CHIKV infection can elicit neutralizing antibodies that persist at high levels for at least eight years, providing evidence to inform the development of vaccines and vaccination strategies.
African swine fever (ASF) continues to inflict severe and persistent damage to the global swine industry and food security. Since 2018, ASF viruses (ASFVs) of genotype II, genotype I, and genotype I/II recombinant with varied virulence have been reported in China. Although several ASF vaccines featuring fluorescent markers have been licensed in neighboring countries, an approved vaccine remains unavailable in China. Therefore, there is an urgent need to establish a rapid detection method to simultaneously monitor the prevalence and fluorescence-tagged ASFVs. Here, we developed a pentaplex quantitative real-time polymerase chain reaction (qPCR) assay targeting the B646L, X64R, MGF_360-14 L, eGFP, and mCherry genes for the simultaneous differential detection of genotype I, II, and I/II recombinant, as well as eGFP- and mCherry- tagged ASFVs. This assay demonstrated no cross-reactivity against seven non-target porcine pathogens. It achieved a limit of detection (LOD) of 50 copies/reaction for each of five plasmid targets and LODs of 0.1–1.0 50% tissue culture infective dose (TCID50)/reaction for genotype I, II, and I/II recombinant ASFVs. In addition, this assay demonstrated an overall concordance of 78% (39/50) with previous triplex qPCR across all 50 clinical samples. Notably, for the subset of samples with B646L cycle threshold (Ct) values <35, the concordance reached 100% (21/21), covering genotype I, II, and I/II recombinant ASFVs. This indicates that the pentaplex qPCR could effectively differentiate clinical samples with Ct values below 35. In conclusion, the pentaplex qPCR assay provides a reliable tool for the simultaneous detection and differentiation of diverse ASFVs (genotype I, II, and I/II recombinant, eGFP- and mCherry- tagged), providing supports for ASF surveillance in China.
The genus Henipavirus includes highly lethal zoonotic pathogens such as Nipah virus (NiV) and Hendra virus (HeV), both classified as Risk Group 4 agents and recognized as priority pathogens by the World Health Organization (WHO). Recent International Committee on Taxonomy of Viruses (ICTV) taxonomic revisions restrict the genus to only bat-borne viruses, with multiple novel henipaviruses identified recently. In this mini-review, we synthesize current knowledge on henipavirus distribution, diversity, and biological risk. Eight members of the genus have been identified to date. HeV remains geographically confined to Australia, whereas NiV circulates in several countries across South and Southeast Asia. Except HeV and NiV, all other members have been detected solely in bats. Phylogenetic analysis confirms their common ancestry; however, unlike HeV, NiV exhibits marked geographic structuring in its lineage divergence. To help assess relative risk, we summarize henipavirus infection spectrum, receptor usage patterns, and pathogenicity, along with the current state of prophylactic and therapeutic interventions, thereby providing a foundation for evidence-based risk classification. Critical knowledge gaps persist for recently discovered viruses, including the lack of live virus isolates and corresponding in vivo data from animal models, precluding definitive risk assessment. Given the increasing frequency of spillover events—highlighted by the 2026 Nipah outbreaks in India and Bangladesh—there is an urgent need to enhance surveillance and characterization of henipaviruses within a One Health framework. This review provides a consolidated reference for understanding the biological risks posed by henipaviruses and aims to inform preparedness efforts against future threats posed by these viruses.
The 2026 Andes virus (ANDV) cluster associated with the merchant vessel (MV) Hondius cruise ship highlights the limitations of hantavirus control strategies that have traditionally focused on rodent-source exposure alone. No evidence supports heating, ventilation, and air conditioning (HVAC)-mediated long-distance ANDV spread. Such strategies are insufficient for ecologically sensitive cruise routes, enclosed ocean-going environments, international passenger movement, and limited onboard medical capacity. Current evidence indicates that ANDV has limited but documented potential for person-to-person transmission. Transmission is most plausibly associated with acute-phase viremia, exposure to body fluids or short-range droplets, prolonged close contact, caregiving, and specific contextual conditions; it should not be equated with sustained community transmission by highly efficient respiratory viruses. On the basis of epidemiologic investigations, clinical shedding studies, animal models, viral genetic evidence, and environmental stability data, this review analyzes how high-consequence pathogens may have their public health impact amplified in cruise-ship settings. It further proposes prevention and control measures covering pre-voyage ecological exposure assessment, embarkation screening, early onboard recognition, tiered isolation, rapid shipboard testing, medical evacuation, and cross-border coordination. The central lesson from the MV Hondius event is that cruise ships operating on ecologically sensitive routes should move beyond conventional sanitation-centered management toward a whole-of-journey biosecurity model based on evidence stratification and graded response.
Isoniazid (INH) remains a cornerstone of tuberculosis (TB) treatment; however, its early bactericidal activity (EBA) and associated adverse effects vary substantially among individuals. Although personalized dosing has been proposed, its clinical implementation remains limited, largely due to incomplete characterization of the predictive factors. This review synthesizes evidence from PubMed-indexed EBA studies of INH to identify key determinants of its variable efficacy and to guide individualized dose selection across different clinical settings. We found that individual N-acetyltransferase 2 (NAT2) acetylator status is a critical predictor of both the EBA of INH and the risk of drug–induced liver injury (DILI). Geographic variation in NAT2 acetylator phenotypes likely explains a substantial proportion of the regional disparities in reported EBA. Additionally, escalating the INH dosage may overcome low–level resistance associated with inhA promoter mutations. In conclusion, personalizing INH dosage based on NAT2 acetylator type—especially for rapid acetylators—and increasing doses to address inhA–mediated resistance may improve therapeutic efficacy and safety. Integrating these host and pathogen factors into clinical practice could help optimize TB treatment outcomes across diverse populations and resistance profiles.
Imported aerosol exposure systems for nonhuman primates are often costly and limited in availability, restricting advanced research on respiratory pathogens. To address this, a domestically developed nose-only aerosol exposure system was systematically evaluated and optimized to enhance performance and accessibility. Comprehensive assessment of aerosol generation, transmission, and sampling components revealed key areas for improvement, which were targeted through four modifications: adoption of a vibrating mesh nebulizer for physiologically relevant particle sizes, reduction of plenum chamber volume to minimize losses, shortening of transmission pathways, and addition of 0.25% newborn calf serum to sampling media for viral preservation. These changes collectively minimized viral viability loss during aerosol delivery. The optimizations resulted in a 2.19 log10-units increase in spray factor (SF), enabling aerosol concentrations to exceed 104.43 50% cell culture infectious dose (CCID50)/L at the exposure port using 107.25 CCID50/mL viral titer in the generator. Functional evaluation with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in cynomolgus macaques (Macaca fascicularis) provided preliminary evidence of feasibility for viral delivery and infection, with detectable viral shedding and seroconversion observed following aerosol exposure. The optimized system represents a domestically developed approach that may complement existing aerosol exposure platforms, addressing challenges related to accessibility and cost. This study provides preliminary evidence supporting the feasibility of this approach for respiratory infectious disease research, with potential applications in vaccine development and pandemic preparedness.
People living with human immunodeficiency virus (HIV) are highly susceptible to opportunistic fungal infections, such as Talaromyces marneffei, Candida, and Pneumocystis jirovecii, primarily due to their immunocompromised status. These infections often manifest as invasive candidiasis, pneumonia, and other severe diseases. Consequently, diagnostic failures for these specific infections remain a leading cause of HIV-related mortality. This review systematically evaluated the currently available diagnostic tools for these pathogenic fungi. Traditionally, etiologic detection, particularly fungal cultivation, has been considered the gold standard for diagnosis. Simultaneously, methods such as microscopic examination, molecular biology tests, and immunological diagnostic technologies are rapidly advancing and becoming increasingly applicable. However, persistent limitations in efficiency, accuracy, reliability, and cost-effectiveness continue to impede clinical diagnosis. This dilemma significantly hampers the advancement of clinical diagnosis for opportunistic fungal infections in HIV-positive populations both in China and globally. Given this diagnostic challenge, there is an urgent need for the further development of novel tools and strategies. These efforts should focus on promoting the identification of molecular targets, innovating targeted probes, exploring detection platforms, and designing diagnostic techniques. Ultimately, improvements in the clinical diagnosis of opportunistic fungal infections will directly contribute to a reduction in the HIV-related mortality rate.
Carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a critical threat to burn patients due to multidrug resistance and high transmissibility. We analyzed CRKP isolates from 15 severe burn victims of a tanker explosion in China, identifying six ST15 strains and one ST273 strain co-harboring blaNDM-5 and mcr-8.1. Genomic analysis revealed that ST15 (KP1) carried the Tn1722-blaKPC-2 transposon and a mutated rmpA2 gene, whereas ST273 (KP6) exhibited colistin resistance. Whole-genome sequencing identified four complete plasmids: ST15 strains harbored blaKPC-2 and rmpA2, and ST273 carried mcr-8.1 and blaNDM-5 on separate plasmids. The mcr-8.1 gene resided on an IncFII(K) / IncFIA(HI1) plasmid with a conserved resistance region, suggesting horizontal transfer potential, while blaNDM-5 on IncX3 plasmids indicates clonal expansion. These findings reveal the genetic complexity and high transmissibility of CRKP strains, highlighting the urgent need for systematic surveillance to prevent the spread of emerging resistance determinants.
ESKAPE, including Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. pose a significant global health threat due to their extensive drug resistance and rapid evolutionary capacity. This article advocates a paradigm shift from conventional antibiotic warfare to “ecological co-management”, integrating four innovative strategies plus an overarching framework: (1) microbiome-based interventions using probiotics, phages, and niche modulation; (2) a One Health 2.0 framework that incorporates wastewater surveillance and artificial intelligence (AI)-driven stewardship; (3) evolutionary constraint methods including anti-virulence agents and clustered regularly interspaced short palindromic repeats (CRISPR)-based targeting; (4) metabolic pathway intervention and antimetabolite therapy such as biotin biosynthesis inhibition; and (5) the establishment of a clinical translation and risk management system for innovative antimicrobial strategies. These multidimensional efforts aim to disrupt resistance transmission, restore antibiotic susceptibility, and promote sustainable pathogen control through ecological and systems-level integration.
