OBJECTIVES: To characterize tuberculous meningitis (TBM)-associated hyponatraemia and better understand its causality, progression, and influence on treatment outcomes. METHODS: 208 Vietnamese adults with TBM, consecutiv...OBJECTIVES: To characterize tuberculous meningitis (TBM)-associated hyponatraemia and better understand its causality, progression, and influence on treatment outcomes. METHODS: 208 Vietnamese adults with TBM, consecutively enrolled into two trials of adjunctive dexamethasone (ACT-HIV:NCT03092817; LAST-ACT:NCT03100786), had at least one measurement of plasma sodium, urinary sodium, serum osmolality, or urine osmolality during treatment. Fluid status was assessed by fluid balance and inferior vena cava ultrasound. TBM severity and clinical endpoints by 12 months were recorded. RESULTS: 176/190 (92.6%) participants with plasma sodium measured at presentation had hyponatraemia, with lower sodium associated with more severe TBM, and increased CSF inflammation. Pre-defined causality criteria applied to 34 participants with complete data suggested 7/34 (20.6%) had cerebral salt wasting (CSW) and 27/34 (79.4%) had the syndrome of inappropriate anti-diuretic hormone (SIADH). Dexamethasone therapy (vs. placebo) was associated with higher plasma sodium during the first 30 days, irrespective of baseline plasma sodium, however these associations did not reach statistical significance. During treatment, lower plasma sodium and higher 24-hour urinary outputs strongly predicted death and neurological events at 3 and 12 months. CONCLUSIONS: Hyponatraemia was strongly associated with more severe TBM and intracerebral inflammation. Persistent hyponatraemia and increasing urinary output during treatment associate with worse clinical outcomes.
BACKGROUND: Coronaviruses such as SARS, SARS-CoV-2 and related Sarbeco-Coronaviruses continue to pose global health threats, underscoring the need for vaccines capable of inducing broad cross-sarbecovirus protection. The...BACKGROUND: Coronaviruses such as SARS, SARS-CoV-2 and related Sarbeco-Coronaviruses continue to pose global health threats, underscoring the need for vaccines capable of inducing broad cross-sarbecovirus protection. The pEVAC-PS vaccine was developed using Digitally Immune Optimised Synthetic Vaccine (DIOSynVax) technology and pre-clinically selected for the ability to induce broadly protective immune responses across the Sarbecoviruses including SARS, SARS-CoV-2, and related viruses representing potential zoonotic spillovers. For this first-in-human study, the antigen was delivered as a DNA vaccine to enable thermostability and needle-free intradermal administration to support future deployment in resource-limited settings. METHODS: This open label phase I dose escalation study investigated the safety, tolerability and immunogenicity of the pEVAC-PS vaccine candidate against SARS, SARS-CoV-2 and related Sarbeco Coronaviruses via needle-free intra-dermal delivery using the PharmaJet Tropis Device. Healthy volunteers aged 18 to 50 who had received two or three prior doses of COVID-19 vaccine, and without recent confirmed COVID-19 infection, were enrolled sequentially to receive a dose escalation regime of 0.2 mg, 0.4 mg, 0.8 mg, and 1.2 mg of pEVAC-PS, administered at day zero and day 28. The primary outcomes were safety and reactogenicity, documented by solicited and unsolicited adverse events, serious adverse events and adverse events of special interest. Secondary outcomes were immunogenicity measured primarily by humoral responses to SARS-CoV-1 and SARS-CoV-2 antigens at day 56 (28 days after the second dose of vaccine). International Clinical Trials Registry Platform registered, ISRCTN87813400. FINDINGS: Between December 2021 and September 2023, a total of 39 volunteers were vaccinated. The vaccine was well tolerated at all four doses with no significant safety concerns elicited. Interpretation of immunogenicity outcomes was influenced by high baseline antibody levels and heterogeneous exposure histories due to ongoing waves of Omicron variant infections during recruitment, which differed across dose-escalation cohorts and introduced unavoidable immune bias. INTERPRETATION: Needle-free intradermal delivery of this novel computationally designed PanSarbeco vaccine was safe and well tolerated. Although immunogenicity was modest in the context of substantial pre-existing immunity, participants developed measurable responses to conserved, vaccine-encoded sarbecovirus epitopes, supporting the feasibility of this antigen design strategy.
Hutton MM, Vink PE, Kuxhausen A
… +11 more, Tsang M, Sánchez Fructuoso A, Robberechts T, Pérez R, Park JB, Ortiz F, Kumar D, Chiang YJ, Atig F, Mwakingwe-Omari A, Zoster-073 study group
OBJECTIVES: Immunogenicity and safety of recombinant zoster vaccine (RZV) were evaluated in the long-term and after revaccination in kidney transplant (KT) recipients on daily chronic immunosuppressive treatment. METHODS...OBJECTIVES: Immunogenicity and safety of recombinant zoster vaccine (RZV) were evaluated in the long-term and after revaccination in kidney transplant (KT) recipients on daily chronic immunosuppressive treatment. METHODS: This phase 3b, single-arm, multicenter trial, evaluated KT recipients for varicella zoster virus (VZV) glycoprotein E (gE)-specific humoral and cell-mediated immune (CMI) responses and safety ∼4-8 years post-primary RZV series (two doses) given at ≥18 years of age; and after revaccination (two doses, one month apart), ∼6-8 years post-primary RZV series. Solicited and unsolicited adverse events (AEs) were recorded for seven and 30 days after each revaccination dose. Serious AEs (SAEs), including biopsy-proven allograft rejection and potential immune-mediated diseases, were recorded throughout the study. RESULTS: 68 participants were enrolled and 47 revaccinated. Persistent humoral and CMI responses remained ≥2.4-fold and ≥6.1-fold above pre-vaccination levels. One revaccination dose provided robust humoral (22.3-fold) and CMI (276.2-fold) above pre-vaccination responses. No vaccine-related SAEs were observed. CONCLUSIONS: This study demonstrates sustained immunogenicity against VZV gE for up to ≥8 years, functional immune memory with a robust anamnestic response at 6-8 years, and an acceptable safety profile after revaccination, reinforcing RZV's value for herpes zoster prevention in adult KT recipients on daily immunosuppression. CLINICAL TRIAL REGISTRATION: NCT04176939.
HIV-2 infection is associated with low-to-undetectable plasma viral load, broad and sustained specific antibody and T cell responses, and a slow course of CD4 T cell decline, even in the absence of antiretroviral therapy...HIV-2 infection is associated with low-to-undetectable plasma viral load, broad and sustained specific antibody and T cell responses, and a slow course of CD4 T cell decline, even in the absence of antiretroviral therapy (ART). Here, we investigated the secondary lymphoid organs of people with HIV-2 (PWH2) as compared to people with HIV-1 (PWH1) and seronegative subjects. We found active HIV-2 replication and major disruption of lymph node architecture in PWH2, also attested by the alterations that we demonstrated in the blood counterparts of follicular T and B cells. These findings were corroborated by in vitro infection assays using tonsil organ cultures and HIV-2 or HIV-1 primary isolates with distinct co-receptor usage, CCR5 or CXCR4, which showed significant HIV-2 cytopathogenicity associated with post-transcriptional control of HIV-2 replication, revealed by high titres of cell-associated viral DNA and mRNA transcripts but reduced HIV-2 protein production. Overall, our findings support a major impact of HIV-2 on secondary lymphoid tissue organisation throughout the disease course, stressing the relevance of this neglected infection to understand host-pathogen equilibrium in retroviral zoonoses and to identify strategies towards a functional HIV cure.
Beltrame A, Giuliano AR, Villa LL
… +16 more, Lazcano-Ponce E, Santana-Bagur J, Allen-Leigh B, Portillo-Romero AJ, Sahasrabuddhe VV, House MG, Brofsky E, Galan de Paula L, Carvalho da Silva RJ, Schell MJ, Rathwell J, Isaacs-Soriano K, Fan W, Mello C, Ellsworth GB, Wilkin T
OBJECTIVES: Assess the distribution of oral HPV genotypes and examine their associations with age and HIV-related factors among men living with HIV. METHODS: This cross-sectional study analyzed baseline data from a rando...OBJECTIVES: Assess the distribution of oral HPV genotypes and examine their associations with age and HIV-related factors among men living with HIV. METHODS: This cross-sectional study analyzed baseline data from a randomized, double-blinded, placebo-controlled Phase III trial ('ULACNet-201'; NCT04255849) assessing the 9vHPV vaccine's efficacy in PLWH. Participants included men aged 20-50 years from Brazil, Mexico, and Puerto Rico, on antiretroviral therapy for ≥6 months. Oral HPV genotypes were assessed using the SPF PCR-DEIA-LIPA on oral gargles. Demographics and HIV-related characteristics were collected via questionnaires, and clinical assessments were conducted. ANOVA and chi-square tests assessed associations with age groups and HPV infection. RESULTS: Among 700 participants, oral HPV was detected in 27.9%, with HR-HPV detection at 11.0%. 4vHPV and 9vHPV types were detected in 4.9% and 8.9% participants, respectively. The most detected HR-HPV types were HPV 16 (2.4%), HPV 33 (2.0%), and HPV 52 (2.0%). No significant age-specific differences in oral HPV detected were observed. Higher detection rates of any HPV and HR-HPV were observed among participants with baseline CD4 counts below 200 cells/mm³ or a history of AIDS-defining conditions. CONCLUSIONS: Oral HPV genotyping in men with HIV reveals distinct oncogenic patterns, underscoring the need to monitor long-term OPSCC risk.
OBJECTIVES: We assessed the effect of early ART during acute HIV infection on reservoir dynamics, cytokine profile, and T-cell metabolism. METHODS: We studied a longitudinal cohort of PWH starting ART during early (ET) o...OBJECTIVES: We assessed the effect of early ART during acute HIV infection on reservoir dynamics, cytokine profile, and T-cell metabolism. METHODS: We studied a longitudinal cohort of PWH starting ART during early (ET) or chronic (CT) infection, and a cross-sectional cohort including matched ET and CT participants (≥36 months virologically suppressed) and HIV-negative controls. We analysed total HIV DNA, intact and defective proviruses, cell-associated HIV RNA, plasma cytokines, and metabolomic profiles of CD4 and CD8 T-cells. RESULTS: Over 75% of ET participants started ART in Fiebig stages IV-VI. Early ART was associated with lower total HIV DNA and cell-associated RNA. Although intact proviruses were similar between groups, they represented a larger proportion of the reservoir in ET participants. Worse pre-ART immune status correlated with a larger and more transcriptionally active reservoir. Regulatory, inflammatory, and homeostatic cytokines negatively correlated with the intact reservoir, particularly in CT participants. Metabolomic profiling of T-cells demonstrated ART timing-dependent alterations in several metabolic pathways. Metabolites involved in glycolysis, amino-acid metabolism, and polyol pathways positively correlated with HIV transcription in CD4⁺ T-cells, especially in CT participants. CONCLUSION: Early ART limits the HIV reservoir size, shapes its composition, and influences immunometabolic pathways, though it might not be enough to reduce the intact reservoir.
OBJECTIVES: Cancer patients are vulnerable to SARS-CoV-2 reinfection due to impaired immunity. We estimated the effectiveness of bivalent COVID-19 vaccination against reinfection in adults with cancer and prior SARS-CoV-...OBJECTIVES: Cancer patients are vulnerable to SARS-CoV-2 reinfection due to impaired immunity. We estimated the effectiveness of bivalent COVID-19 vaccination against reinfection in adults with cancer and prior SARS-CoV-2 infection. METHODS: We conducted a nationwide target trial emulation study using the K-CoV-N cohort, including 84,748 adults with cancer and prior SARS-CoV-2 infection (follow-up: Oct 2022-Jun 2023). The clone-censor-weight method with inverse probability of censoring weights compared bivalent vaccination versus none. SARS-CoV-2 reinfection ≥14 days post-vaccination and ≥90 days after prior infection was the primary outcome. Vaccine effectiveness (VE) was estimated via pooled logistic regression (1-HR). RESULTS: 24.1% received bivalent vaccines. Reinfection risk was 5.2% (bivalent) versus 8.4% (no-bivalent). Overall, VE was 22.2% (95% CI, 15.8-28.2%). Protection was greater among younger adults, those with prior boosters, and those with more distant prior infections (≥1 year). Significant protection was observed in patients with solid tumors, whereas estimates for hematologic malignancies were attenuated and non-significant. CONCLUSIONS: Bivalent vaccination meaningfully reduced reinfection risk among adults with cancer, extending and strengthening the existing evidence base through a causal inference framework. These findings provide real-world evidence to support their continued role in routine and seasonal immunization strategies while highlighting the need for risk-stratified approaches tailored to immune capacity.
Tadesse FG, Chali W, Ejigu LA
… +25 more, Abdo M, Kassa FA, Bulto MG, Bezabih MK, Alemayehu L, Hundera NL, Bayu SL, Nibret D, Ashine T, Assefa M, Solomon Z, Demisse M, Gashaw A, Shimelash A, Tebeje SK, Hailemeskel E, Gadisa E, Rosado J, Obadia T, Taylor AR, White M, Massebo F, Ramjith J, Drakeley C, Bousema T
OBJECTIVES: Plasmodium vivax relapses can lead to episodes of recurrent parasitemia. We longitudinally assessed parasite and gametocyte kinetics and infectivity to mosquitoes during P. vivax recurrent infections in Ethio...OBJECTIVES: Plasmodium vivax relapses can lead to episodes of recurrent parasitemia. We longitudinally assessed parasite and gametocyte kinetics and infectivity to mosquitoes during P. vivax recurrent infections in Ethiopia. METHODS: Patients presenting with clinical P. vivax infections were enrolled at Shele health center in Arba Minch Zuria district, Ethiopia. All participants received chloroquine plus 14-day primaquine for radical cure, and were subsequently followed for one year with scheduled monthly visits. Parasite and gametocyte densities were quantified using molecular assays, and infectivity was assessed through mosquito feeding assays. RESULTS: Over the follow-up period, 54.6% (96/176) of patients experienced at least one recurrent parasitemia. Gametocyte density was similar between baseline and recurrent symptomatic episodes but lower during asymptomatic parasitemia (p<0.001). Across all mosquito feeding assays, 167 (70.2%) of 238 feedings resulted in at least one infected mosquito, with similar proportions between baseline (117 [70.5%] of 166) and recurrent symptomatic infections (50 [69.4%] of 72). Mosquito infection rates were strongly associated with both asexual parasite density (ρ=0.29; p<0.0001; n=166) and gametocyte density (ρ=0.32; p<0.0001) at baseline. Genotyping a subset of recurrent infections indicated 45.7% (42/92) of recurrences were likely to be relapses. After adjusting for gametocyte density, mosquito infection rates appeared lower when feeding on blood of relapsing infections as opposed to new infections (Odds Ratio 0.48, 95% CI 0.26-0.87, p=0.016). CONCLUSIONS: This comprehensive assessment of parasite kinetics and transmissibility over the course of infections uncovers a high frequency of recurring episodes of parasitemia that are accompanied by infectious gametocytes. This work further supports the need to strengthen radical cure to prevent relapsing infections and sustain malaria transmission control.
Jameson G, Batten I, Dyer AH
… +10 more, Geoghegan C, Murray M, McDonnell N, Murphy DM, Connolly SA, McLaughlin AM, Maoldomhnaigh CÓ, Gleeson LE, Keane J, Basdeo SA
RATIONALE: Monocytes are central to host defence against Mycobacterium tuberculosis (Mtb), yet their functional and metabolic profiles during latent TB infection (TBI) and active TB disease (TBD) remain poorly defined. I...RATIONALE: Monocytes are central to host defence against Mycobacterium tuberculosis (Mtb), yet their functional and metabolic profiles during latent TB infection (TBI) and active TB disease (TBD) remain poorly defined. Immunometabolic dysfunction may underlie ineffective responses in TB, but cell-specific mechanisms are unclear. OBJECTIVES: To compare the phenotypic, functional, and metabolic profiles of circulating monocytes from individuals with TBI, TBD, and healthy controls (HC), and assess the impact of treatment. MEASUREMENTS: Peripheral blood monocytes were profiled using high-dimensional flow cytometry, Luminex cytokine/chemokine assays, and SCENITH™, a flow-based metabolic assay. Unstimulated and Mtb-stimulated monocytes from treatment-naïve and treated individuals were analysed. MAIN RESULTS: Monocytes from TBI and TBD showed distinct phenotypes from HC, marked by elevated CD14. HLA-DR was reduced in classical monocytes from TBD compared with both TBI and HC. TNF receptors were downregulated in TBI but unchanged in TBD. Baseline cytokine and chemokine profiles in TBI and TBD were similar (yet distinct from HC), but Mtb stimulation elicited a stronger cytokine response in TBI. Metabolically at baseline, TBI and TBD monocytes exhibited increased glycolysis and reduced mitochondrial dependence versus HC. Treatment partially restored mitochondrial function. Upon Mtb challenge, TBI monocytes had higher glycolytic capacity than HC and TBD. CONCLUSIONS: Monocyte metabolic plasticity and cytokine production distinguish TBI from TBD and are partially reversible with treatment. Circulating monocyte metabolism reflects TB immune status and may serve as a biomarker or therapeutic target. Reprogrammed glycolytic profiles in TBI contrast with impaired adaptability in TBD, suggesting dysfunctional myeloid activation during disease.
BACKGROUND: Acute Respiratory Infection (ARI) is the commonest reason for antibiotic use. Distinguishing bacterial from viral ARI is challenging, leading to antibiotic overuse and antimicrobial resistance. Respiratory vi...BACKGROUND: Acute Respiratory Infection (ARI) is the commonest reason for antibiotic use. Distinguishing bacterial from viral ARI is challenging, leading to antibiotic overuse and antimicrobial resistance. Respiratory viruses detected by PCR in patients with ARI may be causally related, but asymptomatic detection and bacterial co-infection can also occur. Host response profiling may therefore provide insights into the clinical significance of viral detection. METHODS: PAXgene RNA blood samples from patients hospitalised with ARI were tested using the TriVerity test (Inflammatix, Sunnyvale, CA, USA). This host response test measures levels of 29 specific mRNAs to generate separate scores from 1 to 50 indicating the likelihood of bacterial and viral infection (1-10 very low, 11-20 low, 21-30 moderate, 31-40 high, 41-50 very high). Clinical and laboratory data were collected and all patients had PCR testing for respiratory viruses. Scores were compared in patients with and without viral detection and according to virus type. For patient with rhino enterovirus (RhV) detected, scores were compared according to clinical diagnosis. FINDINGS: 169 patients were tested. Median age was 60 (45-74) years, 152 (90%) received antibiotics, and 103 (61%) patients had viruses detected. Median TriVerity viral scores were highest for influenza (44), lowest for RhV (27), and intermediate for other viruses. Evaluating individual virus-infected patients, there was marked heterogeneity in both viral and bacterial scores between patients testing positive for the same viral pathogen. This was most marked for RhV (IQR 15-37). Viral scores for RhV positive patients were higher in patients with a discharge diagnosis of asthma exacerbation, 35 (31-42) compared to exacerbation of COPD, 16 (11-28) and pneumonia, 18 (11-36; p=0·0095) and bacterial scores followed the opposite pattern. INTERPRETATION: Host gene expression scores suggest that the true aetiology of ARI in adults with respiratory viruses detected by PCR is heterogenous, especially for RhV, and that careful interpretation is required before attributing causality. Combining pathogen PCR with host response testing may aid interpretation and could reduce unnecessary antibiotic use.
OBJECTIVES: To analyze the extent and risk factors of household influenza transmission using molecular testing and viral genomes. METHODS: In a community-based cohort in the United States during 2022-2024, participants s...OBJECTIVES: To analyze the extent and risk factors of household influenza transmission using molecular testing and viral genomes. METHODS: In a community-based cohort in the United States during 2022-2024, participants self-collected weekly nasal swabs. Swabs were tested for influenza by RT-PCR; genomic sequencing was performed. Index cases had the first influenza detection within households. Factors associated with household transmission were evaluated using Poisson regression. RESULTS: Influenza transmission was detected in 56/303 influenza-positive households with a distinct index case. Most (82%) index cases were symptomatic; 16% of children vs 28% of adults were asymptomatic. 89/941 household contacts were infected 1-7 days after the index (secondary household infection risk: 9.5%, 95% CI: 7.3, 12.2). Index and secondary case median ages were 11 and 24 years, respectively. A greater proportion of contacts were infected when the index case was symptomatic (11%) vs asymptomatic (5%). Higher viral load was associated with 3.1 (1.7, 5.8) times higher risk of secondary infection. Most (13/16) index-secondary case pairs with available sequences differed by ≤3 nucleotides. CONCLUSIONS: Most household index cases were symptomatic children. Higher viral load and presence of symptoms among index cases were associated with household transmission. Home-based surveillance can assess household transmission using case chronology and genomics.
Beharier O, Guedalia J, Sehtman-Shachar DR
… +11 more, Kerem L, Cahen-Peretz A, Cohen SM, Sompolinsky Y, Hershko Klement A, Shefer G, Melul E, Goldman-Wohl D, Yagel S, Calderon-Margalit R, Lipschuetz M
OBJECTIVE: The COVID-19 pandemic raised concerns regarding the effects of maternal SARS-CoV-2 infection during pregnancy on infant growth and neurodevelopment. Prior evidence has been inconsistent, limited by small sampl...OBJECTIVE: The COVID-19 pandemic raised concerns regarding the effects of maternal SARS-CoV-2 infection during pregnancy on infant growth and neurodevelopment. Prior evidence has been inconsistent, limited by small sample sizes, short follow-up, and confounding by prematurity. We evaluated growth and developmental outcomes through 24 months among term-born children exposed in utero to maternal SARS-CoV-2 infection compared with unexposed controls. METHODS: We conducted a nationwide retrospective matched cohort study including 66,285 term infants born in Israel between March 2020 and March 2022. Maternal SARS-CoV-2 infection during pregnancy defined exposure, with exposed infants (n=22,096) matched to unexposed controls by delivery date. National registries provided standardized growth and developmental data. Outcomes included infant growth and attainment of 31 developmental milestones up to 24 months, analyzed using adjusted stratified Cox regression models. RESULTS: Infant growth trajectories, developmental milestone attainment, and referral rates were similar between exposed and unexposed children. Findings were consistent across sub-analyses by sex, trimester of infection, maternal disease severity, and during the pre-vaccine period. CONCLUSION: This large nationwide study did not identify a significant association between maternal SARS-CoV-2 infection during pregnancy and early childhood growth or development among term neonates. Based on nationwide data with two-year follow-up, these findings offer reassuring evidence regarding outcomes.
OBJECTIVES: Helicobacter pylori (H. pylori) infection is the main driver of gastric cancer, with a step-wise progression via chronic superficial gastritis (CSG), atrophic gastritis (CAG), and intestinal metaplasia (IM)....OBJECTIVES: Helicobacter pylori (H. pylori) infection is the main driver of gastric cancer, with a step-wise progression via chronic superficial gastritis (CSG), atrophic gastritis (CAG), and intestinal metaplasia (IM). While accurate diagnosis of H. pylori infection is central to gastric cancer prevention strategies, current diagnostic methods may vary in sensitivity depending on the presence of gastric precursor lesions. METHODS: In this multicenter prospective study, 462 patients undergoing upper endoscopy at three Chinese hospitals were tested using (rapid urease test [RUT], C urea breath test [UBT], biopsy qPCR, stool antigen test [SAT], serology, hematoxilin & Eosin [H&E] staining, and immunohistochemistry [IHC]). A composite reference defined H. pylori infection as positivity in ≥2 of UBT, SAT, or qPCR, or histological detection via H&E/IHC. RESULTS: Diagnostic performance of H. pylori tests varied per gastric preneoplastic precursor lesion, with the commonly used UBT showing a low sensitivity. qPCR and SAT demonstrated superior overall performance across all stages. Combining SAT with H&E achieved the highest sensitivity (0.848 [0.765; 0.930]), while UBT + SAT offered a robust non-invasive alternative (sensitivity (0.790 [0.713; 0.866]). CONCLUSION: The accuracy of H. pylori tests varies across gastric disease stage. Multimodal diagnostic strategies are needed to improve detection and ensure accurate risk stratification in gastric cancer prevention.
Urogenital infections caused by Neisseria meningitidis (Nm) are increasing globally, yet the prevalence, antimicrobial resistance profiles, and transmission dynamics of Nm in men who have sex with men (MSM) remain poorly...Urogenital infections caused by Neisseria meningitidis (Nm) are increasing globally, yet the prevalence, antimicrobial resistance profiles, and transmission dynamics of Nm in men who have sex with men (MSM) remain poorly defined. We conducted an oropharyngeal carriage study in 174 MSM attending a London sexual health clinic in 2023, prior to the implementation of 4CMenB vaccination and doxycycline post-exposure prophylaxis (doxyPEP). Nm was detected in 21.26% of participants, with carriage significantly associated with throat gonorrhoea, consistent with frequent co-colonisation. Whole-genome sequencing identified diverse lineages, including hyperinvasive clonal complexes (CC)11 and CC4821, and revealed widespread tetracycline resistance: 43% of isolates carried either a conjugative tet(M) plasmid or chromosomal tet(B) efflux locus. These findings indicate that MSM represent an important reservoir of tetracycline-resistant Nm, with the potential amplification of this phenotype following doxyPEP implementation, underscoring the need for genomic surveillance of Neisseria species in sexual networks.
BACKGROUND: While surveillance of invasive pneumococcal disease is well-established in Denmark, monitoring of non-invasive infections is not covered by existing surveillance. We aimed to expand the weekly updated Danish...BACKGROUND: While surveillance of invasive pneumococcal disease is well-established in Denmark, monitoring of non-invasive infections is not covered by existing surveillance. We aimed to expand the weekly updated Danish register-based surveillance system for severe acute respiratory infections (SARI) to cover admissions related to Streptococcus pneumoniae and to investigate the impact of invasive and non-invasive pneumococcal disease during ten years in Denmark from 2015 to 2025. METHODS: We defined 'pneumococcal SARI' as a patient identified in the SARI surveillance system with a relevant non-invasive or invasive microbiological diagnostic test positive for pneumococci. We examined baseline characteristics and severity indicators including length of hospital stay, provision of intensive care treatment and 30-day all-cause mortality, stratified by type of disease. Further, we investigated overall trends and serotype development during the study period. RESULTS: Between 2015 and 2025, we identified 12,185 and 3664 patients with non-invasive and invasive pneumococcal SARI, respectively. Compared with invasive pneumococcal SARI, patients with non-invasive pneumococcal SARI had overall shorter admissions (range 2.5-5.0 days compared with 3.1-7.0 days) and a lower 30-day mortality (range 3.0-13.5% compared with 5.0-21.2% for adults aged ≥50 years). Seasonality was disrupted during the COVID-19 pandemic but restored to pre-pandemic incidence and timing during the post-pandemic years. CONCLUSION: We have built a new system for weekly updated national surveillance that captures both non-invasive and invasive pneumococcal SARI. The system makes it possible to evaluate severity and characteristics of patients and allows for a near real-time monitoring of trends in disease burden of several respiratory pathogens.
Russo A, Gullì SP, Vena A
… +53 more, Spadafora L, Bernardi M, Corcione S, Ceccarelli G, Alessandri F, Mastroianni CM, Oliva A, Venanzi Rullo E, Caviglia G, Cortegiani A, Ippolito M, Nunnari G, Di Gennaro F, Saracino A, Marino A, Cacopardo B, Tiseo G, Falcone M, Galfo V, Iaria C, Pipitone G, Cascio A, Carbonara S, Montemurro L, Serino FS, Boffa N, Libanore M, De Rosa FG, Mattei A, Calabresi A, Tumbarello M, Fontanelli Šuleková L, Pallotto C, Brugnaro P, Mascianà R, Tiri B, Coppola N, Calabria G, Bandera A, Lombardi A, Vassalini P, Carannante N, Scaglione V, Meschiari M, Simonetti O, Mularoni A, Bar F, Serraino R, Mussini C, Bassetti M, Biondi-Zoccai G, Serapide F, ITACA study group
OBJECTIVES: Bacteremia caused by carbapenem-resistant Acinetobacter baumannii (CRAB) is associated with high morbidity and mortality. The primary objective was to identify clinical and therapeutic factors associated with...OBJECTIVES: Bacteremia caused by carbapenem-resistant Acinetobacter baumannii (CRAB) is associated with high morbidity and mortality. The primary objective was to identify clinical and therapeutic factors associated with 14- and 30-day mortality following infection onset. METHODS: This was a prospective, observational, multicenter study conducted across 52 Italian centers. Over an 18-month period, adult hospitalized patients with CRAB bacteremia were enrolled. RESULTS: Among 398 patients with CRAB bacteremia, sources were mainly CVC-related or primary, with 14- and 30-day mortality rates of 22% and 27% respectively. Cox regression analysis identified male sex (p=0.006), and chronic kidney disease (p=0.016) as independent predictors of 14-day mortality, while colistin-containing regimen (p=0.014), and cefiderocol-containing-regimen (p<0.001) were associated with 14-day survival; male sex (p=0.027), septic shock (p=0.018), previous colonization by A. baumannii (p<0.001), and tigecycline-containing regimen (p=0.021) were independent predictors of 30-day mortality, while cefiderocol-containing-regimen (p<0.001) was associated with 30-day survival. Propensity score matching revealed that cefiderocol was significantly associated with 14-day survival and clinical success. The combination of cefiderocol plus Fosfomycin was also significantly associated with clinical success. CONCLUSION: Our findings highlight key clinical and therapeutic determinants of mortality and survival in patients with CRAB bacteraemia, providing valuable insights for improving the management of this challenging infection.
Post-acute sequelae are symptoms that persist or arise after the acute phase of an infection, but their frequency following outbreaks remains poorly understood. Recurrent Lassa fever outbreaks pose a significant public h...Post-acute sequelae are symptoms that persist or arise after the acute phase of an infection, but their frequency following outbreaks remains poorly understood. Recurrent Lassa fever outbreaks pose a significant public health threat in West Africa and may have long-term health effects. This study systematically reviewed the prevalence, incidence, duration, and characteristics of post-acute sequelae in survivors of Lassa virus infection. We searched PubMed and Web of Science up to November 17, 2025. Two reviewers screened and extracted data independently. We included six articles in the review. The most frequently reported post-acute sequela was hearing loss, with a pooled prevalence of 18% (95% CI 9-32) across 6 studies. Odds ratios for the association between Lassa fever and hearing loss were heterogeneous, with a statistically significant positive association in 2 of 5 studies and a positive effect direction in 2 further studies. Of an additional 37 potential post-acute sequelae, several with high prevalence also related to the audiovestibular system (e.g., tinnitus, balance disorder, and vertigo). Our findings highlight that Lassa fever survivors can experience diverse symptoms after recovery from acute infection, with hearing loss being the best-characterised. However, data gaps remain on its incidence after mild infections and its duration. A better understanding of post-acute sequelae after Lassa fever is necessary for accurate disease burden estimation and mathematical modelling studies.