OBJECTIVES: Experimental models suggest that the combined presence of iucA, iroB, peg-344, rmpA, and rmpA2 reliably distinguishes hypervirulent Klebsiella pneumoniae (hvKp) from classical strains (cKp). We evaluated the...OBJECTIVES: Experimental models suggest that the combined presence of iucA, iroB, peg-344, rmpA, and rmpA2 reliably distinguishes hypervirulent Klebsiella pneumoniae (hvKp) from classical strains (cKp). We evaluated the clinical relevance of this five-gene definition among adults with K. pneumoniae bacteremia. METHODS: We performed a longitudinal study in an hvKp-endemic region in adults with community-acquired K. pneumoniae bacteremia. Isolates were classified as hvKp or cKp according to PCR detection of the concurrent presence of five virulence genes. Clinical characteristics and microbiologic features were compared between groups. Predictors of 28-day mortality were identified using logistic regression analysis. RESULTS: Among 602 patients, 254 had hvKp bacteremia. hvKp infections were associated with higher rates of abscess formation and longer hospital stays. After adjustment for confounders, hvKp was an independent predictor of 28-day mortality. Most hvKp isolates were susceptible to commonly used antimicrobial agents. The cKp isolates carrying partial combinations of these virulence genes showed clinical and microbiologic characteristics comparable to those lacking all five genes. CONCLUSIONS: The five-gene hypervirulence profile delineated a clinically more severe subset of K. pneumoniae bacteremia, characterized by higher morbidity and mortality compared with cKp. These findings support the five-gene definition as a robust marker of hvKp in routine practice.
Otten T, Ruijten SDE, Blaauw MJT
… +18 more, Delporte M, Navas A, Vos WA, Groenendijk AL, van Eekeren LE, Vadaq N, Hageman S, Matzaraki V, Richel O, Berrevoets M, Verbon A, Stalenhoef J, Arts R, Lunzen JV, Riksen NP, Vandekerckhove L, Netea MG, van der Ven AJ
BACKGROUND: People with HIV (PWH) using antiretroviral therapy are at increased risk to develop cardiovascular diseases (CVD). We hypothesized that residual viremia (RV; unquantifiable low, but detectable viral load) inc...BACKGROUND: People with HIV (PWH) using antiretroviral therapy are at increased risk to develop cardiovascular diseases (CVD). We hypothesized that residual viremia (RV; unquantifiable low, but detectable viral load) increases CVD risk. METHODS: We enrolled 1895 virally suppressed PWH and compared CVD incidence in participants with and without RV. Extensive multi-omics characterization was performed. Incident CVD was registered after 2-year follow-up and adjusted odds ratios (aOR) calculated accounting for classical CVD risk factors. The numbers of expected and actual CVD events were compared using CVD risk scores. FINDINGS: RV, detected in one-third of participants, strongly increased the risk of developing a first cardiovascular event (3.1% vs 1.2%, aOR 2.8, p=0.004). Participants with RV experienced twice the number of events predicted by the SCORE2 risk model. The association between RV and CVD was not driven by inflammation, immune activation, gut barrier dysfunction, or lipometabolic perturbations. INTERPRETATION: Residual viremia independently associated with CVD development, highlighting the need for tailored prevention and examination of novel intervention strategies.
OBJECTIVES: HIV reservoirs in myeloid cells, including tissue-resident macrophages, persist despite antiretroviral therapy, hindering viral eradication. We have tested an approach for HIV clearance through selective elim...OBJECTIVES: HIV reservoirs in myeloid cells, including tissue-resident macrophages, persist despite antiretroviral therapy, hindering viral eradication. We have tested an approach for HIV clearance through selective elimination of host cells harboring replication-competent HIV (SECH), by inhibition of autophagy and anti-apoptotic molecules during viral reactivation. Whether the SECH approach can effectively target reservoirs of the myeloid lineage is investigated. METHODS: We examined whether SECH treatments could deplete HIV-infected macrophages from HIV donors ex vivo, and in humanized mice in vivo. We also performed spatial transcriptome analyses of myeloid HIV reservoirs in the brains of humanized mice that escaped SECH treatments. RESULTS: SECH treatments can eliminate HIV-infected macrophages from HIV donors ex vivo, and in a portion of humanized mice in vivo. Spatial transcriptome analyses showed increases in epigenetic repressors for HIV transcription, as well as elevated autophagy and glycolysis genes in brain myeloid cells resistant to SECH treatments, while counteracting these molecular mechanisms sensitized the myeloid reservoirs to cell death. CONCLUSIONS: Our data suggest that myeloid HIV reservoirs resistant to depletion display limited HIV gene expression by epigenetic repressors, and express more pro-survival genes, while targeting these mechanisms helps to promote the clearance of myeloid HIV reservoirs.
Perez Mazzali M, Pérez-Cózar F, Cal-Sabater P
… +17 more, Rybakowska P, Tellería P, Gamazo J, De Vicuña MG, Arribas-Rodríguez E, Fiz-López A, de Castro CG, García-Blesa A, Rello SR, De Prado Á, Pérez C, Tamayo E, Orduña A, Dueñas C, Marañón C, Bernardo D, Cuesta-Sancho S
Long COVID is a complex condition characterized by a broad spectrum of persistent, multisystemic symptoms that often impair daily activities and cause disability with significant socioeconomic impact. Although several hy...Long COVID is a complex condition characterized by a broad spectrum of persistent, multisystemic symptoms that often impair daily activities and cause disability with significant socioeconomic impact. Although several hypotheses have been proposed to explain its pathophysiology-including immune dysregulation-the underlying mechanisms remain poorly understood. Indeed, there are no current treatments for this condition. Therefore, we aimed to characterize immune alterations induced by SARS-CoV-2 during the acute phase of infection and three months post-hospital discharge in a cohort of patients who later developed Long COVID, referred to a matched cohort who did not. We performed high-dimensional immune profiling of peripheral blood mononuclear cells using a 40-marker mass cytometry panel. Data analysis combined classical hierarchical gating strategies with unsupervised computational approaches. Our results revealed distinct immune signatures between Long COVID and non-Long COVID patients, affecting both the innate and adaptive immune compartments. Notably, individuals who subsequently developed Long COVID exhibited early abnormalities at infection in innate immunity, particularly involving dendritic cells and γδ T cells. Moreover, three months post-discharge, persistent alterations were observed in several adaptive immune cell subsets in patients who next developed Long COVID over time. In summary, our findings suggest that early immune dysregulation following viral infection may predispose individuals to persistent post-viral pathology.
OBJECTIVES: To explore the trends and patterns of human papillomavirus (HPV) infection in mainland China from 2015 to 2025, and to investigate the distribution of non-infected populations. METHODS: HPV detection data wer...OBJECTIVES: To explore the trends and patterns of human papillomavirus (HPV) infection in mainland China from 2015 to 2025, and to investigate the distribution of non-infected populations. METHODS: HPV detection data were from 27,000 participating hospitals across 341 cities in all 31 provinces, covering 69.2% of hospitals in mainland China. A total of 33,750,381 women who underwent HPV testing between January 2015 and September 2025 were included. The distribution of 17 high-risk genotypes (HPV-16, -18, -26, -31, -33, -35, -39, -45, -51, -52, -53, -56, -58, -59, -66, -68, and -82) and 10 low-risk genotypes (HPV-6, -11, -40, -42, -43, -44, -55, -61, -81, and -83) was assessed by year, age group, and region, respectively. RESULTS: The overall prevalence of HPV infection was 21.81%, with high- and low-risk genotypes being 17.02% and 4.79%, respectively. HPV prevalence generally increased from 7.75% in 2015 to 22.48% in 2025, participants aged less than 20 years (81.46%) exhibited the highest HPV infection burden, and the overall HPV prevalence trended slightly higher in eastern China (22.66%). The most common genotypes were HPV-52 (3.20%), HPV-16 (2.19%), and HPV-53 (1.67%). 51.16% of the participants had infection with one HPV genotype. The distribution of non-infected populations differed across years, age groups, and regions. CONCLUSIONS: The prevalence of HPV infection shows an increasing trend in the past ten years among women in mainland China, with the predominant genotypes being HPV-52, HPV-16, and HPV-53. Our findings highlight the importance of scaling up the HPV vaccination nationwide particularly targeting the youth and eastern China.
Zhang MZ, Wang ZJ, Yu HJ
… +17 more, Wu YF, Du LF, Su XL, Shen SJ, Sun Y, Deng B, Li LJ, Ma K, Pan YS, Xia LY, Zhu DY, Shi W, Cui XM, Zhao L, Jiang JF, Jia N, Cao WC
OBJECTIVES: This study aimed to isolate and systematically characterize the emerging Rickettsia koreansis from ticks in China, define its genomic features, and assess its clinical and epidemiological significance for hum...OBJECTIVES: This study aimed to isolate and systematically characterize the emerging Rickettsia koreansis from ticks in China, define its genomic features, and assess its clinical and epidemiological significance for human health. METHODS: Rickettsiae were isolated from larval Rhipicephalus microplus ticks by cell culture and biologically characterized. Whole-genome sequencing and assembly were performed for phylogenetic analysis. Comparative genomics was used to identify functional features. Human infections were confirmed by pathogen-specific PCR and serological assays, and clinical characteristics were described. Infection prevalence and distribution of ticks were determined. RESULTS: A novel isolate, designated R. koreansis str. TIGMIC YN, was successfully obtained. It exhibited an average nucleotide identity of 99.93% and a digital DNA-DNA hybridization value of 98.1% with the Korean reference strain CNH17-7, indicating that they belong to the same species. Synteny and pangenome analyses revealed that despite extensive structural conservation, TIGMIC YN displays distinctive strain-level adaptation through localized chromosomal rearrangements and unique gene clusters. Through sentinel surveillance, eight laboratory-confirmed human infections were identified, all presenting with mild febrile illness or other nonspecific symptoms. Among 554 tick samples, R. koreansis was detected in seven tick species, with an overall infection rate of 27.4%, across ten provinces or autonomous regions in China. CONCLUSION: R. koreansis's broad vector range, defined genomic features, and demonstrated human infectivity underscore the need to strengthen epidemiological surveillance, develop specific diagnostic tools, and improve clinical recognition of infections caused by this pathogen.
OBJECTIVES: China still faces a heavy Tuberculosis (TB) burden; extensively drug-resistant tuberculosis (XDR-TB) prevalence rises sharply amid overall TB decline, with no national/provincial comprehensive assessment of i...OBJECTIVES: China still faces a heavy Tuberculosis (TB) burden; extensively drug-resistant tuberculosis (XDR-TB) prevalence rises sharply amid overall TB decline, with no national/provincial comprehensive assessment of its trends and drivers hampering targeted control and resource allocation. This study analyzes 1990-2023 XDR-TB indicators to support precision TB control. METHODS: The data of study was from Global Burden of Disease Study (GBD) 2023 and Chinese Center for Disease Control and Prevention. The analyzed indicators include age-standardized rates (ASR) and absolute case numbers for incidence, prevalence, mortality, disability-adjusted life years (DALYs), years of life lost (YLL), and years lived with disability (YLD). Joinpoint regression models were used to analyze the changing trends of XDR-TB burden indicators from 1990 to 2023 and calculate the annual percentage change. RESULTS: In 2023, the age-standardized incidence rate (ASIR) of XDR-TB in China was 0.143 per 100,000 population (95% UI: 0.017, 0.436), with 2436 cases (95% UI: 296, 7697). The age-standardized mortality rate (ASMR) was 0.018 per 100,000 population (95% UI: 0.002, 0.066), with 388 deaths (95% UI: 44, 1408). From 1990 to 2023, XDR-TB in China exhibited an increasing trend in ASIR (AAPC = 7.134, 95% CI: 5.766, 8.503), age-standardized prevalence rate (ASPR, AAPC = 7.800, 95% CI: 7.022, 8.578), ASMR (AAPC = 1.762, 95% CI: 0.778, 2.747). Xinjiang ranking first in ASIR, ASPR, and ASYLDR. Tibet ranked first in ASMR, ASDR, and ASYLLR. Xinjiang led in deaths, DALYs, and YLL cases. From 1990 to 2023, all 33 administrative regions in China showed an increasing trend in XDR-TB indicators, with Hong Kong, Macao, and western regions such as Tibet and Xinjiang experiencing the largest increases in these ASR, with Hong Kong's ASIR, Macao's ASPR, and Tibet's ASDR showing the fastest growth. CONCLUSION: The geographic disparities and age distribution patterns of XDR-TB in China provide a foundation for precision control strategies. Particular attention is needed for the western regions, especially Xinjiang and Tibet. Future efforts should focus on targeted interventions in high-risk areas and strengthening prevention measures for the elderly to further reduce the XDR-TB burden.
OBJECTIVES: We aimed at estimating the frequency of local transmission of arboviral infections in Verona province, Italy, between June and September 2025. METHODS: People presenting with acute fever and without recent tr...OBJECTIVES: We aimed at estimating the frequency of local transmission of arboviral infections in Verona province, Italy, between June and September 2025. METHODS: People presenting with acute fever and without recent travel history (and less than WBC 10,000 per µL, unless there was a history of tick bite) were screened for arboviruses following a multi-step protocol. Cases were confirmed by a molecular assay and/or virus-specific IgM antibodies, including rising antibody titre in a second serum sample collected 15-20 days later and a positive seroneutralization test. RESULTS: One hundred and two people were included. Of these, 29 out of 102 (28.4%, 95% CI 20.2-38.4%) demonstrated autochthonous arboviral infections. Specifically, three cases of West Nile fever, four cases of tick-borne encephalitis, and 22 cases of chikungunya infections were diagnosed. CONCLUSIONS: A large proportion of unexplained acute fever cases had arboviral infections from local transmission. Of note, the protocol permitted an early detection of a local outbreak of chikungunya. These findings support the importance of strengthening public health surveillance in southern Europe, for an early detection of transmission foci and to adapt screening protocols to the changing epidemiology of arboviral infections.
Mazarakis N, Toh ZQ, Neal E
… +19 more, Nguyen C, Bright K, Luu S, Quah L, Ng YY, Hart J, Do LAH, Rudel A, Dassanayake S, Higgins RA, Carissa R, Ong DS, Justice F, Moore KA, Watts E, Subbarao K, Mulholland K, von Mollendorf C, Licciardi PV
OBJECTIVES: We report immunogenicity, safety, and efficacy over 12 months following a fourth COVID-19 mRNA or protein vaccine dose. METHODS: Adults aged ≥18 years were randomised 1:1 to receive a bivalent mRNA vaccine (m...OBJECTIVES: We report immunogenicity, safety, and efficacy over 12 months following a fourth COVID-19 mRNA or protein vaccine dose. METHODS: Adults aged ≥18 years were randomised 1:1 to receive a bivalent mRNA vaccine (mRNA-1273.214/mRNA-1273.222, Moderna; n=177) or a protein vaccine (NVX-CoV-2373, Novavax; n=176). A self-selected control group (no fourth dose) was also recruited (n=143). Follow-up occurred at six- and 12-months post-vaccination. Geometric mean concentrations (GMCs) of anti-Spike binding IgG and surrogate neutralising antibodies to Ancestral and Omicron variants (BA.1, BA.4/5 and JN.1), and IFN-γ concentrations (IGRA) as a proxy for T cell immunity were compared between the study groups. RESULTS: The IgG levels against Ancestral strain were higher in the Moderna group than the Novavax group at six- [Geometric mean ratio (GMR): 1.59, 95% CI: 1.38 to 1.82] and 12-months post-vaccination (GMR: 1.34, 95% CI:1.16 to 1.55), and similarly for Omicron BA.1, BA.4/5 and JN.1 variants (six months: ranged from GMR: 1.62 to 1.66, 95% CI: 1.41 to 1.91; 12 months: ranged from GMR: 1.33 to 1.43, 95% CI: 1.15 to 1.67). Similar results for neutralising antibodies were also observed. However, no differences in IGRA were observed between Moderna and Novavax. The IgG GMCs against Ancestral strain and Omicron variants in both vaccine groups were higher than the control group at both timepoints (six months: ranged from GMR: 1.24 to 2.40; 12 months: ranged from GMR: 1.04 to 1.62). As a post-hoc analysis, 68.1% (94/138) in the control group, had a SARS-CoV-2 infection over the 12-month period, compared with 43.0% (74/172) and 47.0% (77/164) in the Moderna and Novavax group, respectively. CONCLUSIONS: While the bivalent Moderna vaccine induced higher immune responses than the Ancestral Novavax vaccine as a fourth dose, both vaccines appeared to provide comparable protection against SARS-CoV-2 Omicron variants over 12-months.
OBJECTIVES: Beijing, a large urban center with complex food supply chains, faces increasing challenges from foodborne Campylobacter infections. However, local data on antimicrobial resistance, source attribution, and pat...OBJECTIVES: Beijing, a large urban center with complex food supply chains, faces increasing challenges from foodborne Campylobacter infections. However, local data on antimicrobial resistance, source attribution, and pathogenic characteristics remain limited. This study aimed to clarify long-term trends, resistance patterns, and likely infection sources of Campylobacter in Beijing to inform prevention and treatment strategies. METHODS: From 2016 to 2023, 27,691 stool samples were collected from patients with foodborne diseases in 45 hospitals across Beijing. Campylobacter isolates were recovered and identified, followed by antimicrobial susceptibility testing, and whole-genome sequencing. A core-genome MLST-based extreme gradient boosting (XGBoost) model was applied for machine-learning source attribution. RESULTS: A total of 1204 Campylobacter isolates were identified, including 1005 C. jejuni, 198 C. coli and one C. fetus. The proportion of C. coli increased compared with the early surveillance years and reached its highest level in 2023. Both C. jejuni and C. coli showed >90% resistance to fluoroquinolones and tetracyclines, and C. coli has a much higher resistance rate to macrolide. Machine-learning analysis identified chicken as the major source for C. coli infections, accounting for 75.76% cases. CONCLUSIONS: This 8-year genomic surveillance highlights the sustained and increasing contribution of C. coli and extensive resistance in Beijing, supporting targeted control measures and antibiotic stewardship in foodborne disease management.
Löwa A, Budt M, Balázs A
… +21 more, Sikora V, Melzer M, Rubil T, Pfeiffer AE, Fischer M, Mieth M, Hellwig K, Wyler E, Diel DG, Tönnies M, Bauer TT, Graff M, Neudecker J, Rückert JC, Mall MA, Gruber AD, Landthaler M, Buchauer L, Hippenstiel S, Wolff T, Hocke AC
OBJECTIVES: To evaluate the impact of the 2018 switch from PCV13 to PCV10 in Sweden's childhood immunisation programme on the serotype distribution of Streptococcus pneumoniae. METHODS: Respiratory tract (RT) S. pneumoni...OBJECTIVES: To evaluate the impact of the 2018 switch from PCV13 to PCV10 in Sweden's childhood immunisation programme on the serotype distribution of Streptococcus pneumoniae. METHODS: Respiratory tract (RT) S. pneumoniae isolates (n=1615; 2020-2023) were serotyped, tested for antimicrobial susceptibility and compared with invasive pneumococcal disease (IPD) isolates (n=397) and PCV13-era data (2016-2018). RESULTS: Predominant serotypes were 3 (13%), 19A (11%), 23B (10%), and 11A (7.5%). PCV10 coverage was low (4.1%), but increased with PCV13 (29%), PCV15 (30%), PCV20 (47%) and PCV21 (71%). After reintroduction of PCV10, the proportions of serotypes 3 (8.7% to 13%) and 19A (4.5% to 11%) increased (p<0.001), and an increase in serotype 19A was also observed in IPD (5.6% to 19%, p<0.001). Serotype 8 dominated IPD (21%) but was uncommon in RT isolates (2.8%). Among RT isolates, reduced benzylpenicillin susceptibility was observed in 11%. Resistance was highest to trimethoprim/sulfamethoxazole (13%), followed by erythromycin (9.3%), tetracycline (8.5%), and clindamycin (6.9%). Multidrug- and extensively drug-resistant isolates were uncommon (7.9% and 1.1%) and were predominantly serotypes 15A and 19A. CONCLUSIONS: Serotypes 19A and 3 re-emerged as predominant, indicating the need for continued surveillance. Our study emphasises the risk of rapid serotype resurgence when lower-valency vaccines are reintroduced.