Ran J, Zhu L, Ning M
… +19 more, Zhang W, Zhang W, Liu P, Yin S, Zhang J, Chu J, Qin Y, Shi C, Wei Y, Cai Q, Guo C, Qian C, Gao J, Pu W, Zhang F, Tong X, Wu C, Huang R, Chen Y
OBJECTIVES: To characterize SARS-CoV-2-specific humoral and cellular immunity in a large community cohort, focusing on age-related differences following hybrid immunity from prior infection and vaccination. METHODS: In t...OBJECTIVES: To characterize SARS-CoV-2-specific humoral and cellular immunity in a large community cohort, focusing on age-related differences following hybrid immunity from prior infection and vaccination. METHODS: In this cross-sectional study, 1186 adults (median age: 62 years, IQR 43-73) were enrolled from six districts in Jiangsu province, eastern China. Spike-specific immune responses including serum total antibodies (Abs), nasal secretory IgA (sIgA), memory B cells, circulating follicular helper T (cTfh) cells, and CD4⁺/CD8⁺ memory T cell subsets were evaluated. Multivariable logistic regression identified factors associated with immune responses. RESULTS: Compared with younger adults, individuals aged ≥65 years exhibited significantly lower levels of spike-specific serum total Abs, spike-specific memory B cells, spike-specific cTfh cells, and spike-specific CD4 terminally differentiated effector memory T (T) cells, but significantly higher levels of spike-specific CD8 T cells (all P < 0.05). Spike-specific nasal sIgA, CD4⁺/CD8⁺ T and T subsets were comparable between age groups. After adjustment for sex, infection history, vaccination status, body mass index (BMI), diabetes, and lifestyle factors, age ≥65 years was associated with reduced spike-specific total Abs (OR 0.653, 95% CI 0.512-0.839), memory B cells (OR 0.780, 95% CI 0.613-0.992), and cTfh cells (OR 0.706, 95% CI 0.554-0.899). In contrast, older age was associated with elevated spike-specific CD8⁺ T cells (OR 1.396, 95% CI 1.096-1.778). CONCLUSIONS: Despite widespread hybrid immunity, older adults displayed impaired humoral and T-B helper responses alongside selective expansion of spike-specific CD8⁺ T cells. These findings define an age-associated immune phenotype in the endemic phase and support age-tailored vaccination and immune monitoring strategies.
Cao L, Kong D, Lou J
… +26 more, Wang X, Yang F, Ye Y, Zhang Z, Yao X, Ye J, He J, Zhang Y, Su S, Zheng H, Liu C, Zhang Z, Shi X, Wan J, Liu W, Fu Y, Wu C, Tang J, Li H, Li Y, Huang Y, Lu J, Zou X, Hu Q, Wang MH, Lv Z
BACKGROUND: In July 2025, a large chikungunya outbreak occurred in southern China, with more than 5,000 cases reported within a single month. However, the genomic basis of this urban outbreak remains poorly characterised...BACKGROUND: In July 2025, a large chikungunya outbreak occurred in southern China, with more than 5,000 cases reported within a single month. However, the genomic basis of this urban outbreak remains poorly characterised. METHODS: A total of 804 CHIKV-positive clinical specimens were collected through routine surveillance and outbreak investigations by the Shenzhen Center for Disease Control and Prevention. Following whole-genome sequencing and quality control, 614 genomes were retained and analysed in combination with 1,105 publicly available CHIKV genomes sampled globally between 1953 and 2025. Comprehensive genetic analyses were performed to characterise lineage origin, transmission dynamics, and short-term genomic diversification across local and global scales. RESULTS: All outbreak sequences belonged to the East/Central/South African (ECSA) lineage, specifically clustering within the Middle African lineage (MAL) sub-lineage, and formed a well-supported, genetically compact monophyletic group. Within this cluster, genomes diversified rapidly into multiple co-circulating subclusters over a short time window (August-October), indicating continued regional transmission and geographic structuring during outbreak expansion. Despite this rapid expansion, genetic variation remained limited, with only a small number of characteristic amino-acid substitutions identified, most of which were present at low to moderate frequencies and showed no evidence of widespread fixation across the outbreak population. The inferred substitution rate for the outbreak-associated lineage was 9.90 × 10⁻⁴ substitutions per site per year (95% HPD: 8.28-11.69 × 10⁻⁴). CONCLUSIONS: These findings suggest that large CHIKV outbreaks in highly connected metropolitan settings can arise from the rapid expansion of a single contemporary genetic background, even in the absence of extensive adaptive change. This study provides a high-resolution genomic perspective on CHIKV spread and highlights key features of short-term viral diversification during outbreaks.
OBJECTIVES: To investigate the long-term evolution of neutralizing antibody responses after BA.5/BF.7 breakthrough infection (BTI) in previously vaccinated individuals. METHODS: We conducted a 2.5-year longitudinal study...OBJECTIVES: To investigate the long-term evolution of neutralizing antibody responses after BA.5/BF.7 breakthrough infection (BTI) in previously vaccinated individuals. METHODS: We conducted a 2.5-year longitudinal study of 29 individuals who experienced BA.5/BF.7 BTI in late 2022 in China. Neutralizing antibody titers against D614G and Omicron subvariants (BA.5, XBB.1.5, EG.5.1, KP.2, KP.3, XEC, and LB.1) were measured prior to BTI, at approximately three weeks post-BTI, and at serial timepoints over the subsequent two years. RESULTS: Before BTI, individuals had limited neutralization titers to D614G and undetectable titers against Omicron subvariants. Approximately three weeks after BTI, neutralizing titers against D614G and BA.5 increased significantly, whereas titers to XBB.1.5, EG.5.1, KP.2, KP.3, XEC, and LB.1 increased but remained low. Over the following two years, the neutralizing titers to D614G and BA.5 gradually declined, whereas cross-reactive titers against Omicron subvariants increased progressively. By 2.5 years post-BTI, neutralizing titers against all tested variants had almost reached comparable levels. CONCLUSIONS: Long-term neutralizing antibody response after BA.5/BF.7 BTI is characterized by gradual broadening of cross-neutralization, and convergent antibody titers against Omicron subvariants, possibly driven by repeated infections. These findings provide crucial insights into long-term antibody response after repeated antigen exposure and inform the design of vaccination strategies.
Clostridioides difficile infection (CDI) is an antibiotic-associated diarrheal disease. Mixed infection has been previously reported. However, its clinical implications are not well defined. In this study, we evaluated t...Clostridioides difficile infection (CDI) is an antibiotic-associated diarrheal disease. Mixed infection has been previously reported. However, its clinical implications are not well defined. In this study, we evaluated the presence of multi-strain (MS) isolates in fecal specimens from patients diagnosed with CDI at a tertiary hospital in Virginia. C. difficile colonies (three per sample) were obtained from fecal specimen cultures (N=174) from patients diagnosed with CDI from April 2021 to February 2022. The toxin gene profile of each isolate was determined by PCR using specific primers for triose phosphate isomerase (tpi), toxin A (tcdA), toxin B (tcdB), binary toxin A (cdtA), and binary toxin B (cdtB). A subset of fecal specimens (n=62) with Ct values ≤ 25 for tcdB underwent total bacterial isolation in TCCFA and were processed for whole-genome shotgun sequencing. Based on the toxin gene profile of each isolate, MS infection was identified in 32.8% (57/174) of patients. Among all the isolates (N=522), tcdAtcdBcdtAcdtB (32.38%), tcdAtcdBcdtAcdtB (32.18%), and tcdAtcdBcdtAcdtB (28.5%) were the most common toxin gene profiles identified. An analysis of clinical data of 160 patients showed that age, gender, recurrence, severity of disease, mortality, and being infected by a strain expressing the binary toxin gene did not distinguish between being infected by MS or SS (single strain). Among the MS cases (N=52), the presence of non-toxigenic strains decreased the risk of severe CDI (p=0.0098). Whole-genome shotgun sequencing analysis confirmed mixed infection in our cohort and identified that the C. difficile strains S-0352 (clade 1, ST2) and W0023a (clade 1, ST42) are the most common sequence types in MS and SS cases, respectively. Overall, our findings indicated a high prevalence of MS infection among C. difficile-infected patients, and a non-toxigenic C. difficile strain association with less severe disease in MS cases. These results suggest that specific strains may differentially predominate in MS or SS infection and that the presence of non-toxigenic C. difficile strains in MS infection influences disease severity. The impact of MS infection on the outcomes of anti-C. difficile treatments warrant further investigation.
BACKGROUND: Drug-induced liver injury (DILI) management during tuberculous meningitis treatment may result in premature rifampicin and isoniazid withdrawal and contribute to poor outcomes. METHODS: Adults with tuberculou...BACKGROUND: Drug-induced liver injury (DILI) management during tuberculous meningitis treatment may result in premature rifampicin and isoniazid withdrawal and contribute to poor outcomes. METHODS: Adults with tuberculous meningitis, enroled into the ACT HIV (N=520) and LAST ACT (N=720) corticosteroid trials (NCT03092817;NCT03100786), who developed DILI were randomised to strategy-1: continue all drugs, unless ALT ≥10x upper limit of normal [ULN], bilirubin ≥43µmol/L, or symptoms worsen; or strategy-2: stop pyrazinamide, unless ALT ≥5x ULN by day 6, bilirubin ≥43µmol/L, or symptoms worsen; or strategy-3: stop rifampicin, isoniazid, pyrazinamide, continue ethambutol, add levofloxacin and aminoglycoside. The primary outcome was the proportion of time, 60-days following DILI randomisation, during which neither rifampicin nor isoniazid were given (or the participant died). Secondary outcomes included acute liver failure, and death/new neurological events. RESULTS: Sixty-seven participants with DILI were randomised to strategy-1 (n=21), 2 (n=21), and 3 (n=25). Participants had fewer days without rifampicin and isoniazid in strategy-1 (median 7 days [1st-3rd quartile 0-31]) and 2 (9 days [0-21]) than strategy-3 (18 days [11-35]; p=0.022 and p=0.041). No participants developed liver failure. Strategy failure (requiring strategy-3 switch) occurred in 8/21 (38.1%) strategy-1 and 13/21 (61.9%) strategy-2. New neurological event or death after DILI randomisation, until 12 months from primary randomisation, occurred in 7/21 strategy-1, 9/21 strategy-2 and 14/25 strategy-3 (p=0.20 strategy 1 vs. 3; p=0.42 strategy 2 vs. 3). CONCLUSIONS: DILI management strategies that increase transaminase drug-stopping thresholds (10X ULN), or stop pyrazinamide alone, appeared safe and reduced rifampicin/isoniazid interruptions vs. standard approaches.
Albanell-Fernández M, Vergara A, Cardozo C
… +20 more, Herrera S, Verdejo MÁ, Malano-Barletta D, Pitart C, Hernández-Meneses M, Cuervo G, Garcia-Vidal C, López N, Del Río A, Espasa M, Casals C, Morales FJ, Juan P, García F, Mensa J, Morata L, Tuset M, Ulldemolins M, Bodro M, Soriano Á
OBJECTIVES: Persistent candidemia is traditionally defined as ≥5 days of positive blood cultures (BC), although emerging evidence suggests that earlier clearance may influence outcomes. We aimed to identify an earlier th...OBJECTIVES: Persistent candidemia is traditionally defined as ≥5 days of positive blood cultures (BC), although emerging evidence suggests that earlier clearance may influence outcomes. We aimed to identify an earlier threshold associated with 30-day mortality to enable timely interventions and to explore predictors of its occurrence. METHODS: Single-center retrospective study evaluating the frequency and prognostic impact of persistent Candida spp. bloodstream infection. Persistent candidemia was defined using follow-up positive blood cultures (FUPBC) and after initiation of active antifungal therapy (FUPBC-ATF). The primary objective was the earliest FUPBC and FUPBC-ATF thresholds predicting 30-day mortality after adjusting for relevant variables, and the secondary objective was the identification of predictors that may predict its occurrence. In both cases, a multivariable logistic regression was applied. RESULTS: A total of 493 patients with candidemia were analyzed. The earliest cutoffs associated with increased adjusted 30-day mortality were ≥2 days for FUPBC (37.9% vs. 20.3%, p=0.001) and ≥1 day for FUPBC-ATF (33.4% vs. 20.3%, p=0.026). Additional variables associated with 30-day mortality were septic shock and neutropenia. Factors associated with persistence included female sex, cancer, total parenteral nutrition, mechanical ventilation, abdominal source, and rapid time-to-positivity, whereas primary candidemia and N. glabratus were protective. CONCLUSION: Persistent candidemia was associated with 30-day mortality. A duration ≥2 days provides the earliest and most informative cutoff for predicting 30-day mortality. This threshold allows clinicians to rapidly identify high-risk patients and take timely interventions to mitigate adverse outcomes. We propose that an earlier cutoff could better define persistent candidemia.
Atukorale VN, Kwong JC, Hernandez A
… +18 more, Moineddin R, Lee N, Kopp A, Andrew MK, Bronskill SE, Brown KA, Daneman N, Deeks SL, Johnstone J, McGeer AJ, McNally JD, Mubareka S, Murti M, Smieja M, Wilson SE, Zahariadis G, Bolotin S, Buchan SA
OBJECTIVES: We describe the burden of respiratory syncytial virus (RSV)-related hospitalization among community-dwelling older adults in the pre-vaccine era and identify factors associated with adverse hospital outcomes....OBJECTIVES: We describe the burden of respiratory syncytial virus (RSV)-related hospitalization among community-dwelling older adults in the pre-vaccine era and identify factors associated with adverse hospital outcomes. METHODS: We conducted a population-based retrospective cohort study among adults aged ≥50 years hospitalized with RSV, using linked laboratory and health administrative data in Ontario, Canada during 2017-2020. We used modified Poisson regression models to assess associations between 25 individual factors and four hospital-related outcomes (30-day mortality, intensive care unit [ICU] utilization, hospital length of stay [LOS], and 30-day readmission). RESULTS: Of 3221 adults hospitalized with RSV, 314 (9.7%) died within 30 days, 560 (17.4%) required ICU care, and the median (interquartile range) LOS was 6 (3-11) days. Of 2913 adults discharged alive, 343 (11.8%) were readmitted within 30 days. Frailty strongly predicted all outcomes: mortality (adjusted risk ratio [aRR]=1.36; 95%CI, 1.05-1.76), ICU (aRR=1.45; 95%CI, 1.22-1.73), LOS (adjusted incidence rate ratio [IRR]=1.96; 95%CI, 1.81-2.12), and readmission (aRR=1.46; 95%CI, 1.14-1.87). Adults aged ≥90 years (aRR=2.37; 95%CI, 1.32-4.24), those with active cancer (aRR=1.63; 95%CI, 1.17-2.27) or other immunodeficiencies (aRR=1.54; 95%CI, 1.21-1.95), and chronic home care recipients (aRR=1.32; 95%CI, 1.03-1.67) had a higher risk of mortality, with similar trends observed for readmission. CONCLUSIONS: RSV causes substantial morbidity and mortality among hospitalized older adults. These findings help identify high-risk groups for vaccine prioritization.
BACKGROUND: Hand, foot, and mouth disease (HFMD), particularly EV-A71, has caused large-scale epidemics in the Asia-Pacific region, with China alone reporting over 2 million annual cases and causing a substantial morbidi...BACKGROUND: Hand, foot, and mouth disease (HFMD), particularly EV-A71, has caused large-scale epidemics in the Asia-Pacific region, with China alone reporting over 2 million annual cases and causing a substantial morbidity and mortality. While EV-A71 vaccination was introduced in 2016 and COVID-19 non-pharmaceutical interventions (NPIs) were implemented from 2020-2022, comprehensive evidence on their independent and combined effects on HFMD epidemiology remains scarce. We aimed to quantify the impact of vaccination, NPIs, and post-pandemic policy relaxation on HFMD incidence and pathogen distribution. METHODS: We conducted an interrupted time series segmented regression analysis using a 14-year surveillance dataset (January 2011-December 2024) from Beijing's National Notifiable Disease Reporting System and citywide pathogen surveillance network. The study population included all HFMD cases reported in Beijing. We defined four intervention periods: baseline (pre-vaccination), vaccination introduction (August 2016), stringent NPIs (January 2020), and reopening (January 2023). Primary outcomes were HFMD incidence rates and incidence rate ratios (IRRs). We estimated prevented cases under counterfactual scenarios. RESULTS: Among 324,623 reported HFMD cases across the 14-year study period, interrupted time series regression demonstrated that vaccination was associated with a 33% reduction in incidence (IRR 0.67, 95% CI: 0.49-0.91); cumulatively over 8 years (2016-2024), this was estimated to have prevented 23.8% of cases that would have occurred without vaccination. Stringent NPIs were associated with an 84% reduction (IRR = 0.16, 95% CI: 0.06-0.41); cumulatively, during the intervention period (2020-2022), NPIs were estimated to have prevented 82.6% of cases. Following policy relaxation, incidence rebounded 2.53-fold (95% CI: 0.64-9.92), although this increase did not reach statistical significance. In absolute terms, monthly mean case counts declined from 3001 (baseline) to 1886 following vaccination introduction (37.2% decrease), and further to 299 during stringent NPIs (90.0% decrease from baseline), before surging to 1503 post-reopening, a fivefold increase from the NPI period. Pathogen surveillance revealed EV-A71 prevalence declined from 30.5% (baseline) to 4.5% (vaccination period), while coxsackievirus A6 emerged as the dominant serotype, from 9.5% (baseline period) to 56.2% (vaccination period). CONCLUSIONS: EV-A71 vaccination and NPIs were each associated with reduced HFMD transmission, but policy relaxation was followed by a substantial resurgence. The observed serotype replacement with non-vaccine-type enteroviruses highlight critical gaps in current prevention strategies. Sustaining HFMD control requires optimizing vaccine design, developing multivalent vaccines, maintaining high coverage, and integrating targeted NPIs during high-transmission seasons.
OBJECTIVES: Causes of pharyngotonsillitis in Africa, beyond Streptococcus pyogenes, are poorly understood. We aimed to describe the prevalence of S. pyogenes, Fusobacterium necrophorum, and Streptococcus dysgalacatiae su...OBJECTIVES: Causes of pharyngotonsillitis in Africa, beyond Streptococcus pyogenes, are poorly understood. We aimed to describe the prevalence of S. pyogenes, Fusobacterium necrophorum, and Streptococcus dysgalacatiae subspecies equisimilis (SDSE) in children in The Gambia and evaluate the usefulness of clinical decision rules, originally developed for S. pyogenes or beta-haemolytic streptococci, for their prediction. METHODS: We conducted a case-control study on causes of pharyngotonsillitis in children (0-15 years). Samples from age-matched cases and asymptomatic controls were included from two previous studies in The Gambia, conducted June 2021 to September 2022. Pharyngeal swabs were analysed with multiplex-PCR, targeting S. pyogenes, F. necrophorum, and SDSE. Cases and controls were compared, and performance of clinical decision rules evaluated. RESULTS: Only S. pyogenes was more frequently detected among cases (N=376) than controls (n=105) (32% vs. 11%, p<0.0001). No difference was seen for F. necrophorum (9% vs. 10%, p=0.95) or SDSE (11% vs. 14% p=0.19). Clinical decision rules poorly predicted any of the pathogens. CONCLUSIONS: S. pyogenes was the only pathogen more prevalent among cases. F. necrophorum was more common in pharyngeal samples from children in The Gambia than previously described in high-income countries, yet neither F. necrophorum or SDSE differed between cases and controls.
Alanio A, Boukris-Sitbon K, Obadia T
… +12 more, Desnos-Ollivier M, Garcia-Hermoso D, Letscher-Bru V, Desoubeaux G, Guemas E, Durieux MF, Morio F, Robert-Gangneux F, Bonhomme J, Lanternier F, Lortholary O, French RESSIF Study Group
BACKGROUND: Pneumocystis pneumonia (PCP) is a well-known infectious complication of organ transplantation requiring prophylaxis at least within the first 6 month to 1 year post transplantation. RESEARCH QUESTION: Few dat...BACKGROUND: Pneumocystis pneumonia (PCP) is a well-known infectious complication of organ transplantation requiring prophylaxis at least within the first 6 month to 1 year post transplantation. RESEARCH QUESTION: Few data exist comparing the characteristics of Pneumocystis pneumonia associated with kidney, heart, liver or lung transplant recipients. STUDY DESIGN & METHOD: We here conducted a cross-sectional study nested within the surveillance of our national reference center for invasive mycoses to analyze the prospectively declared cases of PCP occurring in solid organ transplant recipients over a period of 11 years. RESULTS: We found that the median occurrence of PCP post-transplantation varies from the organ recipients with PCP occurring earlier in liver recipients and later in other organs reaching a median of 3.9 years in kidney recipients. We also found a clear increase the proportion of positive mycological criteria in PCP cases occurring within 2 years post-transplantation. Age and ICU hospitalization were major variables associated with 3 month-mortality with liver and lung recipient having a better outcome than renal transplant patients upon adjustment including age. A trend toward the role of additional risk factors (such as HIV, Cancer of hematological malignancy) in the outcome of PCP was also observed. INTERPRETATION: Altogether, this study described on a large patient cohort, some key mycological and clinical information associated with PCP in solid organ transplant patients. The characteristics of PCP in kidney and heart recipients seems similar.
OBJECTIVES: To provide updated, national estimates of the burden and secondary-care costs of respiratory syncytial virus (RSV) hospitalisations among adults aged ≥40 years in England, using data from 2023/24, the last se...OBJECTIVES: To provide updated, national estimates of the burden and secondary-care costs of respiratory syncytial virus (RSV) hospitalisations among adults aged ≥40 years in England, using data from 2023/24, the last season before the UK implemented its adult RSV vaccination programme, given that, while the burden of RSV is well established in young children and older adults, it remains less well characterised in working-age adults. METHODS: We analysed adults admitted to hospital with an acute respiratory infection (ARI) using aggregated Hospital Episode Statistics (HES) data for England, 2023/24. RSV, influenza, and COVID-19 hospitalisations were identified using validated International Classification of Diseases, Tenth Revision (ICD-10) codes. Incidence proportion was calculated per 100,000 population by age group. To adjust for potential under-recognition of RSV among ARI admissions without an identified pathogen, proportional-redistribution methods were applied. Hospital costs were estimated using Healthcare Resource Group (HRG) emergency tariffs weighted by clinical presentation. RESULTS: In 2023/24, 803,088 ARI admissions occurred among adults ≥40 years; 18% had a viral and 79% an unspecified aetiology recorded. RSV accounted for 4836 admissions (16 per 100,000 population) based on primary diagnosis. After proportional redistribution to account for under-recognition, this increased to an estimated 23,407 admissions (75.9 per 100,000 population; £68.5 million), which we consider the base estimate. In an expanded scenario including all recorded diagnoses, RSV admissions were estimated at 25,264 (82 per 100,000 population; £74 million), of which approximately £54 million may be attributable to unrecognised cases. Around one-third of total estimated RSV-related costs occurred in adults aged 40-74 years. RSV incidence increased steeply with age, reaching its highest levels in adults aged ≥85 years. CONCLUSIONS: RSV poses a substantial, under-recognised hospital burden in English adults and associated healthcare costs. Increased testing and improved coding and surveillance, particularly for adults aged 40-74 years, are needed to accurately measure potential impact of vaccination and guide prevention policy.
BACKGROUND: Mycoplasma pneumoniae pneumonia (MPP) is a leading cause of community-acquired pneumonia in children. The COVID-19 pandemic substantially disrupted the transmission dynamics of M. pneumoniae, yet large-scale,...BACKGROUND: Mycoplasma pneumoniae pneumonia (MPP) is a leading cause of community-acquired pneumonia in children. The COVID-19 pandemic substantially disrupted the transmission dynamics of M. pneumoniae, yet large-scale, nationwide data characterizing the clinical and epidemiological evolution of pediatric MPP in China across the pandemic period remain scarce. METHODS: We analyzed 325,781 MPP hospitalizations from 31 tertiary children's hospitals across mainland China between 2016 and 2023, using the FUTURE Database. Temporal trends and demographic differences in disease severity, co-infections, complications, length of stay (LOS), and hospitalization costs were systematically evaluated. RESULTS: MPP admissions peaked in 2023, accounting for 8.76% of all pediatric hospitalizations. The male-to-female ratio was 1.15:1. children aged 3-6 years accounted for the largest proportion (32.42%), though children aged 6-10 years became predominant in 2023. Severe MPP increased significantly over time (P for trend <0.0001), rising from 3.78% in 2017 to above 13% after 2020. Viral and bacterial co-infection rates rose significantly to 24.13% and 10.09% in 2023, with infants bearing the highest burden. Respiratory complications increased over time to over 10% after 2021, while extrapulmonary complications declined. The median LOS was 7 days (IQR 5-9), and the median cost was 5891.61CNY (IQR 4427.86-8425.95), both decreased significantly from 2016 to 2023. Severe MPP and coinfections were associated with longer LOS and higher costs. CONCLUSIONS: This nationwide multicenter study reveals a post-pandemic surge in pediatric MPP in China, with rising severity, a shift towards school-aged children, and increasing co-infection rates. Despite improved healthcare efficiency, growing clinical complexity demands enhanced surveillance, risk stratification, and public health preparedness.
BACKGROUND: Large language models (LLMs) have potential to provide clinical infection advice, but variations in prevalent pathogens and antimicrobial resistance requires models to be adapted to local contexts. We evaluat...BACKGROUND: Large language models (LLMs) have potential to provide clinical infection advice, but variations in prevalent pathogens and antimicrobial resistance requires models to be adapted to local contexts. We evaluated a retrieval-augmented generation (RAG) approach to provide antibiotic and infection advice explicitly constrained to local guidelines. METHODS: Relevant guideline sections from Oxford University Hospitals were identified combining keyword-matching and a medical embedding model. A locally-deployed LLM (gpt-oss-20b) generated answers using the retrieved context. Performance was assessed using 200 simulated questions with an LLM-as-judge, and 66 human-written questions reviewed by ≥2 infection specialists. RESULTS: The model attempted to answer 186/200 (93%) simulated clinical advice queries, of which 162 (87%) responses were judged fully-correct, 14 (8%) partially-correct, and 10 (5%) incorrect. Performance was lower in complex scenarios, e.g., when renal impairment was present. For 57 human-written questions covered by guidelines, 46 (81%) single-stage responses were fully-correct and 10 (18%) partially-correct. Of 9 out-of-scope questions, 5 (56%) were correctly identified. A multi-stage pipeline modestly improved performance (84% fully-correct). Median answer generation time was 12 s (single-stage) and 15 s (multi-stage). LLMs without RAG-based local guideline context had lower performance: 21/186 (11%) answers to simulated questions fully correct with the same locally-deployed LLM and 92/200 (46%) with a current frontier model (gpt-5.4). CONCLUSION: An LLM grounded in local antimicrobial guidelines can deliver mostly accurate, concise infection advice but still generates occasional errors and does not always recognise out-of-scope queries. Further optimisation and safety mechanisms are required before routine clinical deployment.
Molès JP, D'Ottavi M, Rutagwera D
… +17 more, Kania D, Tassembedo S, Mennecier A, Sakana BLD, Chunda-Liyoka C, Wilfred-Tonga MM, Fao P, Matoka B, Ousmane TA, Tylleskär T, Kankasa C, Van de Perre P, Nagot N, Mwiya M, PROMISE-EPI Trial Group, Scientific Advisory Board, Data Safety Monitoring Board
OBJECTIVES: Infant postnatal prophylaxis (PNP) is universally recommended for all breastfed infants born from mothers living with HIV up to 6-weeks of age. Continuation of PNP was recommended for infants defined as at hi...OBJECTIVES: Infant postnatal prophylaxis (PNP) is universally recommended for all breastfed infants born from mothers living with HIV up to 6-weeks of age. Continuation of PNP was recommended for infants defined as at high-risk of HIV acquisition. We hypothesised that a single maternal viral load (mVL) at the end of the universal PNP period can accurately identify infants requiring extended prophylaxis. METHODS: We assessed 1398 VL of breastfeeding mothers from Zambia and Burkina Faso at baseline (week 6-8), months 6 and 12 post-partum. Infants were defined at high-risk of HIV acquisition when mVL was ≥ 1000 cp/mL. RESULTS: Mothers with a VL between 40 and 1000 cp/mL or ≥ 1000 cp/mL at baseline were 6 [95CI 3.7-9.6] or 18 [95CI 12.6-25.7] times more likely to have a VL above 1000 cp/mL during breastfeeding than mothers with a VL below 40 cp/mL. A 40 cp/mL threshold for mVL showed a better performance to identify infants eligible for extended PNP in comparison with the standard threshold. CONCLUSION: A single mother VL at W6-8 enabled a sensitive identification of infants at risk of HIV acquisition throughout the breastfeeding period. This conclusion may pave the way for a simplified risk-stratified guideline for the initiation of extended infant PNP.
BACKGROUND: Enteroviruses (EVs) are the major pathogens causing viral encephalitis and meningitis and frequently drive outbreaks in high-risk settings such as schools and healthcare facilities. We analyzed outbreaks repo...BACKGROUND: Enteroviruses (EVs) are the major pathogens causing viral encephalitis and meningitis and frequently drive outbreaks in high-risk settings such as schools and healthcare facilities. We analyzed outbreaks reported from 1960-2025 to map epidemiology, clinical manifestations, and serotypes, informing prevention and control. METHODS: We systematically searched Web of Science, PubMed, CNKI, and Wanfang from 1960 to July 1, 2025 using the keywords of enterovirus, encephalitis, meningitis and outbreak to assemble a global dataset of enterovirus encephalitis and meningitis outbreaks. Eligible studies must report outbreaks of laboratory-confirmed enterovirus meningitis or encephalitis, while those with unclear outbreak definitions or no laboratory confirmation were excluded. Standardized forms were used to extract information on outbreak characteristics, case demographics, and etiology data. A random-effects model was employed to derive combined estimates of attack rates, hospitalization rates, clinical manifestations and serotype distribution, with subgroup analyzes by geographic region, temporal period, and age group. This research was registered in PROSPERO (CRD420251140412). RESULTS: A total of 56 outbreaks (28,622 cases) across 20 countries were included. Outbreaks were most prevalent in the Western Pacific and Europe, exhibiting seasonal peaks in June-July (Northern Hemisphere) and April-May (Southern Hemisphere), with a median size of 90 cases. Schools and medical institutions were the major outbreak settings. EV-B was the dominant species (94.6%, 53/56), with E30 being the most prevalent serotype. Two decades, 2000-2009 and 2010-2019, saw the highest number of reported outbreaks. The overall attack rate was estimated at 13.2% (95% CI 6.1-22.3). Notably, the pooled hospitalization rate was exceptionally high at 94.0% (95% CI 85.9-99.2). The most frequently reported symptoms were fever, headache, and vomiting. CONCLUSIONS: Enterovirus encephalitis and meningitis outbreaks remain a persistent global concern, marked by high hospitalization rates, summer-autumn peaks and regional patterns. They primarily affect children under 15 years old, with multiple serotypes in circulation. Shifting toward active syndromic and genomic surveillance, alongside targeted prevention in high-risk settings, is urgently needed. FUNDING: This work was supported by the Beijing Natural Science Foundation (L242052) and National Key R&D Program of China (2024YFC2310403); Jiangsu Province 333 Project.
OBJECTIVES: The diagnosis of febrile urinary tract infection (fUTI) by urine culture is hampered by antibiotic pre-treatment. We investigated urine metagenomics to diagnose fUTI in patients with positive blood but negati...OBJECTIVES: The diagnosis of febrile urinary tract infection (fUTI) by urine culture is hampered by antibiotic pre-treatment. We investigated urine metagenomics to diagnose fUTI in patients with positive blood but negative urine cultures. METHODS: We performed shotgun metagenomic sequencing on 41 culture-positive and 19 culture-negative urine samples from fUTI patients, comparing urine metagenomics to blood and urine culture including antimicrobial susceptibility testing (AST). mOTUs3.1 performed metagenomic pathogen detection and ResFinder2.0 antimicrobial drug resistance (AMR) gene detection (standard settings). Whole genome sequencing (WGS) was performed on blood culture isolates from culture-negative urine samples. BWA-MEM and sylph aligned metagenomic pathogen reads to their respective WGS assemblies. RESULTS: Metagenomics detected the blood culture isolate in 39/41 culture-positive and 17/19 culture-negative urine samples. 11/19 urine culture-negative patients were pre-treated with antibiotics, versus 8/41 urine culture-positives. The blood culture isolate was the most abundant pathogen in 33/41 culture-positive and 15/19 culture-negative urine samples. A median of 93.2% of pathogen-specific metagenomic reads mapped to their WGS assemblies with a median ANI of 98.7% (n=11). Genotypic AMR detection and phenotypic AST matched in 38-96% of cases. CONCLUSIONS: Urine metagenomics successfully detected the causative pathogen in urine culture-negative fUTI patients. Genotypic AMR prediction requires further investigation.