Harris R, Thirard R, McBrien C
… +15 more, Middleditch A, Chadwick D, Jackson J, Moran E, Perry J, Payne RA, Goodman AL, Cosgrove C, Lillie P, Emmett S, Finn A, Pike K, Culliford L, Lazarus R, ZosterFluCov Trial team
BACKGROUND: Coverage of the recombinant herpes zoster vaccine (RZV) could be improved by coadministration with seasonal vaccines. We evaluated the immunogenicity and safety of co-administration of the first or second dos...BACKGROUND: Coverage of the recombinant herpes zoster vaccine (RZV) could be improved by coadministration with seasonal vaccines. We evaluated the immunogenicity and safety of co-administration of the first or second dose of RZV with an adjuvanted quadrivalent influenza vaccine (aQIV), or mRNA COVID-19 vaccine. METHODS: A multicentre, randomised, controlled, non-inferiority phase 4 trial with masking, across 13 sites. Healthy adults ≥50 years were randomised (1:1:2:2:2) to one of five groups. Co-primary immunogenicity outcomes were evaluated one month after the relevant vaccine: RZV by anti-gE Ig; COVID-19 by anti-S Ig; and aQIV by haemagglutinin antibody inhibition titres. The co-primary safety outcome was grade 3/4 solicited systemic reaction(s) in the seven days after vaccination. RESULTS: Between 15/10/2023 and 27/02/2025 967 participants were recruited (median age 60.5 years, 55% female). Non-inferiority was indicated for all coprimary immunogenicity outcomes, i.e. the lower limit of 95% confidence intervals exceeded the pre-specified non-inferiority criteria (geometric mean ratio=0.67). Rates of the primary safety outcome were low, albeit slightly increased with co-administration; maximum 3.3% for co-administration of RZV/COVID-19, minimum 1.2% for COVID-19 alone. CONCLUSIONS: COVID-19 vaccine and aQIV can be safely co-administered with both doses of RZV without impacting the immunogenicity of any of the vaccines.
OBJECTIVES: To identify and validate plasma host-response protein biomarkers that improve discrimination of bacterial infection in febrile infants ≤90 days of age, and to assess whether novel biomarkers add value beyond...OBJECTIVES: To identify and validate plasma host-response protein biomarkers that improve discrimination of bacterial infection in febrile infants ≤90 days of age, and to assess whether novel biomarkers add value beyond established markers. METHODS: Sub-study of the prospective multicentre Febrile Infant Diagnostic Assessment and Outcome (FIDO) cohort. Novel biomarkers were identified through plasma proteomic profiling (Olink®) and combined with biomarkers and signatures from the literature for verification using Luminex and ELISA platforms. Diagnostic performance of novel biomarkers, established markers (CRP, PCT), and multi-protein signatures was evaluated. RESULTS: Proteomic profiling of 110 samples identified 174 proteins differentially expressed between bacterial and viral infections, revealing distinct pathogen-specific immune signatures. Verification in the full cohort (n = 445) demonstrated PCT had the highest individual accuracy for invasive bacterial infection (IBI) (AUC 0.89). Combining PCT with novel biomarkers, particularly lipocalin-2 (LCN2), improved discrimination (AUC 0.96). Diagnostic performance for the combined IBI/urinary tract infection (UTI) outcome was consistently lower (AUC <0.8). CONCLUSIONS: Febrile infants demonstrate biologically coherent host-response signatures that can be leveraged diagnostically. A PCT-LCN2 combination showed excellent accuracy for identifying IBI and may support future biomarker-guided diagnostic strategies, while reliable discrimination of UTI remains challenging.
Carter EC, Fernandez C, Lim C
… +51 more, Bharucha T, Atomode A, Defres S, Brodsky M, Goodall J, Hall J, Lau E, Vail D, Francis R, Berry L, Malkawi K, Odone J, Richards A, Molai M, Seager E, Chan C, Farrukh S, Gurney R, Price A, Blackaby J, Maxwell A, Mooney C, Dayalan N, Bracchi M, Thompson JV, Upton R, Lawal A, MacFarlane L, Peel A, Olaifa A, Hale A, Reed T, Kunst H, Tiberi S, Hunter M, Dedicoat M, Sharrocks K, Cajic V, Wiselka M, Riste M, Barrera M, Papineni P, Brown J, Collini P, Backx M, Rosser A, Lillie P, McGann H, Morton B, Walsh C, McGill F
OBJECTIVES: The aim of this study was to evaluate the incidence, clinical presentation, risk factors, management, and outcomes of paradoxical reaction (PR) in central nervous system tuberculosis (CNS TB) in the United Ki...OBJECTIVES: The aim of this study was to evaluate the incidence, clinical presentation, risk factors, management, and outcomes of paradoxical reaction (PR) in central nervous system tuberculosis (CNS TB) in the United Kingdom. METHODS: We conducted a retrospective cohort study in 20 UK hospitals, including all patients diagnosed with CNS TB between 2017 and 2022, with 12 months follow-up. Clinical, microbiological and imaging data were collected from patient records. RESULTS: 229 adult patients without HIV were included and 19 patients with HIV in a subgroup analysis. 21% (49/229, 95% CI 16.3-27.3%) of patients developed PR which was associated with worse outcomes, including disability, longer hospitalisation, and neurosurgical intervention. Risk factors for PR included Mycobacterium tuberculosis positive cerebrospinal fluid (CSF), severe disease, and higher CSF neutrophils. 40% (20/50) of patients with PR received host directed therapy (HDT). CONCLUSIONS: We present, to our knowledge, the largest cohort study of CNS TB from a high resource setting. We found a high incidence of PR associated with worse outcomes and variation in management. Our findings highlight the need for randomised controlled trials of HDT in PR which would most likely be conducted in high burden, low-resource settings, so should ensure sustainable access to HDT.
OBJECTIVES: Systematic evaluations of targeted next-generation sequencing (tNGS) for lower respiratory tract infections (LRTIs) remain limited. This study assesses tNGS diagnostic performance and clinical utility. METHOD...OBJECTIVES: Systematic evaluations of targeted next-generation sequencing (tNGS) for lower respiratory tract infections (LRTIs) remain limited. This study assesses tNGS diagnostic performance and clinical utility. METHODS: We prospectively analyzed bronchoalveolar lavage fluid (BALF) from 1251 patients with LRTIs, comparing tNGS results against conventional culture and galactomannan (GM) testing. RESULTS: tNGS achieved a significantly higher pathogen positivity rate than culture (95.6% vs 25.7%, p < 0.0001), with an agreement of 25.2%; stratified agreement was 50.9% for bacteria and 63.5% for fungi. For bacterial targets, tNGS showed 92% positive percent agreement (PPA) and 92% negative percent agreement (NPA); fungal targets showed 74% PPA and 95% NPA. For AMR determinants, the PPA and NPA relative to phenotypic resistance were 72% and 79%, respectively; PPA was 71% for carbapenem resistance and 100% for mecA/C. Higher semiquantitative tNGS levels were significantly associated with culture positivity overall and for bacterial and fungal targets. Clinically adjudicated PPV was 80.3% for tNGS-positive findings, with higher PPV for bacterial than fungal targets (77.3% vs 18.2%). Overall concordance between tNGS and GM for Aspergillus was 84.2%. tNGS positively influenced clinical outcomes in 69.6% of patients and prompted antibiotic adjustments in 42.7%. CONCLUSIONS: In LRTIs, tNGS is significantly more sensitive than culture with high qualitative accuracy. Although it effectively guides clinical decision-making, caution is warranted when using tNGS to predict carbapenem resistance or to initiate antifungal therapy.
BACKGROUND: The paradigm of cervical cancer screening is undergoing a significant global shift. Meanwhile, China has been advancing its national immunization strategy for human papillomaviruses (HPV). However, large-scal...BACKGROUND: The paradigm of cervical cancer screening is undergoing a significant global shift. Meanwhile, China has been advancing its national immunization strategy for human papillomaviruses (HPV). However, large-scale, real-world epidemiological studies that systematically characterize the distribution of HPV genotypes across various cervical cytological findings remain limited. This study aims to evaluate the prevalence and genotype distribution of HPV infection in China over the past five years and to assess the epidemiological patterns across different cervical cytology grades, which may inform the optimization of screening protocols and vaccination policies in the Chinese population. METHODS: De-identified data from 1,191,312 women aged 20-79 years undergoing routine co-testing for HPV genotypes and cervical cytology across 26 provinces in China from January 2020 to December 2024 were analyzed. Cervical exfoliated cell samples were collected and tested for 23 HPV genotypes using the same DNA test kit and liquid-based cytology test under the same procedure. HPV genotypes were classified based on cervical cancer risk: high-risk (HR-HPV) and low-risk (LR-HPV). Cervical cytology categories were classified as negative for intraepithelial lesion or malignancy (NILM), and atypical squamous cells of undetermined significance or worse (ASC-US+). Weighted prevalence of HPV infection was standardized by age group and province. The distribution of HPV genotypes was stratified by cytology grades. RESULTS: The overall weighted prevalence of any-type HPV infection was 17.0% (95% CI: 16.8-17.3%), with HR-HPV at 13.1% and LR-HPV at 6.0%. Regarding regional variations, women from the northeastern and northwestern regions exhibited the highest prevalence of any-type HPV infection and HR-HPV infection. The most prevalent HPV genotypes were HPV 52 (3.36%), HPV 16 (2.56%), and HPV 58 (2.46%). And the most common co-infection pairs were HPV 52-HPV 53, HPV 16-HPV 52, HPV 16-HPV 58. HPV infection prevalence increased significantly with cytological abnormality, from 11.4% in NILM to 73.0% in ASC-US+. HPV infection in the NILM group showed a bimodal age distribution, with prominent peaks observed in the 20-24 and 60-64 years. Notably, a U-shaped distribution was seen for HR-HPV in women with ASC-US+. The genotype distribution shifted from dominance by HPV 52 and 58 in the NILM group to HPV 16 in the ASC-US+ group. CONCLUSION: This nationwide study indicates a considerable burden of HPV infection in China, distinguished by the prominent prevalence of genotypes HPV 52 and HPV 58 in addition to the globally dominant HPV 16. Dynamic changes in the prevalence and genotype distribution of HPV infection across cytology grades suggest the importance of genotype-specific risk stratification in cervical cancer prevention strategies. These findings provide evidence supporting the implementation of national HPV vaccination and cervical cancer screening programs in China.
OBJECTIVES: Infections involving enteric bacteria commonly cause hospitalisation and death in long-term residential aged care (LTC) populations. The risk of such infections has been linked with antibiotic-associated depl...OBJECTIVES: Infections involving enteric bacteria commonly cause hospitalisation and death in long-term residential aged care (LTC) populations. The risk of such infections has been linked with antibiotic-associated depletion of gut anaerobic commensals and the resulting increase in asymptomatic carriage of gut pathobionts. We sought to determine how antibiotic characteristics, particularly activity against anaerobes, influence pathobiont prevalence in LTC residents. METHODS: Stool samples from 164 LTC residents (median age: 87.9 years, interquartile range: 81.3-93.0 years) underwent metagenomic analysis. Associations between prior antibiotic exposures (categorised according to anaerobe coverage and type) and gut microbiome characteristics were explored using multivariable models. RESULTS: Of the 164 participants, 138 (84.1%) carried at least one enteric pathobiont. Compared to those with no prior antibiotic exposure, treatment with anaerobe covering (EAC) antibiotics was associated with higher rates of pathobiont carriage (β=1.36, P=0.010) and higher overall pathobiont relative abundance (β=3.53, P=0.013). In contrast, exposure to antibiotics with limited anaerobe coverage (LAC) showed no such associations. Investigation of commonly prescribed EAC and LAC antibiotics (amoxicillin-clavulanate and cefalexin, respectively) were consistent with these findings, with higher detection (β=1.60, P=0.007) and relative abundance (β=3.32, P=0.039) of pathobiont species in amoxicillin-clavulanate recipients. Pathobionts with greater representation included both species with inherent resistance (i.e. Enterococcus faecium) and sensitivity (i.e. Klebsiella pneumoniae) to amoxicillin-clavulanate. CONCLUSIONS: Antibiotics that deplete commensal anaerobes are associated with pathobiont prevalence in the gut, even where pathobiont species are sensitive to the administered antibiotic. Off-target disruption of commensal anaerobes should be considered when selecting antibiotic treatments, particularly for LTC individuals.
OBJECTIVES: Febrile illness without clear localisation presents a significant diagnostic challenge due to non-specific symptoms and diverse aetiologies. Spiroplasma ixodetis, an emerging tick-associated pathogen previous...OBJECTIVES: Febrile illness without clear localisation presents a significant diagnostic challenge due to non-specific symptoms and diverse aetiologies. Spiroplasma ixodetis, an emerging tick-associated pathogen previously linked mainly to congenital cataracts, has not been well characterised in adults. We investigated the prevalence and clinical features of S. ixodetis infection in adults with acute febrile illness without localisation. METHODS: Shotgun metagenomic sequencing identified S. ixodetis in the initial 209 patient cohort and the sequences were used to developed a novel real-time PCR assay targeting the 23S rRNA gene. Initial cohort screening was followed by testing 128 patients from an additionally selected targeted cohort. Positive results were confirmed by sequencing of 16S and 23S rRNA genes. RESULTS: S. ixodetis DNA was confirmed in 7.2% patients from the initial and in 35.2% patients from the additional cohort (60 in total). All were identified in the period from April to October and 57% reported a recent tick-bite. Clinical presentation was homogenous, characterised by fever, headache, bicytopenia and liver enzyme abnormalities. Outcomes were favourable, with 15% requiring hospitalisation. CONCLUSION: This study identifies S. ixodetis as a previously unrecognised cause of adult febrile illness without localisation, bridging the gap between previously published data between tick studies and isolated human case reports.
OBJECTIVES: Information on influenza vaccine-effectiveness amongst children in tropical regions with year-round influenza transmission remains scarce. We evaluated real-world influenza vaccine-effectiveness in a tropical...OBJECTIVES: Information on influenza vaccine-effectiveness amongst children in tropical regions with year-round influenza transmission remains scarce. We evaluated real-world influenza vaccine-effectiveness in a tropical setting amongst children aged under 5. METHODS: Population-based retrospective cohort study, including all Singaporean children aged under 5, from 1st May 2022-30th April 2024. Person-time was divided into vaccinated (<365 days prior) and unvaccinated categories (no prior vaccination/vaccinated≥365 days prior). Vaccination was classified using national registries. Overlap-weighted Cox regression was utilised to evaluate hazards-ratio (HR) of influenza hospitalisation between vaccinated/unvaccinated groups; vaccine-effectiveness was calculated as 1-HR. Waning of protection in vaccinated children was evaluated via logistic regression, using weeks 2-9 post-vaccination as reference. RESULTS: 196,593 children contributed 137,758 vaccinated and 245,952 unvaccinated observations over 80,839,605 person-days. Overall vaccine-effectiveness was 53% (95%CI=44%-60%). However, relative-vaccine-effectiveness (rVE) waned to 21% of baseline (95%CI=12-36%) by weeks 39-52 post-vaccination. In vaccine-naïve individuals, rVE declined to 11%(95%CI=3-36%) of baseline at weeks 39-52 following a single vaccine dose, whereas rVE declined to 13%(95%CI=4-43%) of baseline at weeks 39-52 after two-dose primary vaccination. CONCLUSION: Vaccination conferred real-world protection amongst children aged under 5 in a tropical setting; though protection waned rapidly. Benefit of a two-dose primary-series might be more marginal in tropical settings.
BACKGROUND: Streptococcus pneumoniae, Staphylococcus aureus, and Klebsiella pneumoniae are the principal pathogens responsible for fatalities due to lower respiratory infections (LRIs), which pose a significant global he...BACKGROUND: Streptococcus pneumoniae, Staphylococcus aureus, and Klebsiella pneumoniae are the principal pathogens responsible for fatalities due to lower respiratory infections (LRIs), which pose a significant global health burden. During 2020 and 2021, the COVID-19 pandemic substantially altered the pathogenic landscape of LRIs. However, the specific impacts on S. pneumoniae, S. aureus, and K. pneumoniae have yet to be clearly determined. This study aims to analyze the changes in disability-adjusted life years (DALYs) associated with LRIs caused by these pathogens from 1990-2021, with a particular focus on the effects of the COVID-19 pandemic. METHODS: We analyzed data on the DALY burden of LRIs attributable to S. pneumoniae, S. aureus, and K. pneumoniae from the Global Burden of Disease Study 2021, covering various geographic and demographic levels, including global, regional, national, age, and sex groups. To assess the overall trend, we calculated the estimated annual percentage change (EAPC) and used Joinpoint regression analysis to determine the annual percent change (APC) for local trends. Additionally, autoregressive integrated moving average (ARIMA) and Bayesian age-period-cohort (BAPC) models were utilized to forecast the age-standardized DALY rates (ASDRs) of the three pathogens through 2030. RESULTS: From 1990-2021, the ASDR for S. pneumoniae LRIs decreased the most significantly, dropping from 1249.50 per 100,000 population (95% UI: 1097.12-1415.86) in 1990 to 309.90 per 100,000 population (95% UI: 264.44-357.22) in 2021. In contrast, the ASDR for K. pneumoniae LRIs decreased from 281.51 per 100,000 population (95% UI: 242.56-321.31) in 1990 to 99.46 per 100,000 population (95% UI: 84.65-115.82) in 2021. S. aureus LRIs showed the slowest decline, with its ASDR decreasing from 242.89 per 100,000 population (95% UI: 216.69-270.69) in 1990 to 156.80 per 100,000 population (95% UI: 139.44-176.08) in 2021. East Asia experienced the most rapid decrease in the ASDR from 1990-2019 and was the only region with an increase during the COVID-19 pandemic (2019-2021). Pacific island nations, including Tokelau and Niue, experienced significant increases in ASDR during the pandemic. Vulnerable populations included children under five years of age and elderly individuals, with males facing a greater burden. Whereas the ASDR trends for S. pneumoniae LRIs and K. pneumoniae LRIs consistently declined, S. aureus LRI trends were irregular. The pandemic accelerated the reductions in ASDR for S. aureus LRIs and K. pneumoniae LRIs but slowed the decline in S. pneumoniae LRIs. By 2030, the ASDRs for these pathogens are projected to continue to decline, albeit at a slower pace for S. aureus LRIs. CONCLUSION: Over the past 32 years, public health initiatives targeting LRIs caused by S. pneumoniae and K. pneumoniae have significantly progressed, demonstrating effective control and management strategies. In contrast, the management of S. aureus LRIs remains less effective, indicating a need for enhanced focus and resources. The recurrent and increasing impact of S. pneumoniae LRIs during seasonal epidemics and pandemics highlights the urgency of prioritizing this pathogen in public health strategies. Despite the rising threat, the potential of S. aureus to become a leading cause of LRI-related DALY burden is often overlooked, underscoring the critical need for increased public health investment. Additionally, the public health infrastructure in small island nations is particularly vulnerable, emphasizing the need for targeted improvements to bolster their crisis management capabilities.
OBJECTIVES: To identify biological, operational, and contextual risk factors associated with fatal and outbreak outcomes following accidental laboratory-associated incidents worldwide. METHODS: We analysed 1126 laborator...OBJECTIVES: To identify biological, operational, and contextual risk factors associated with fatal and outbreak outcomes following accidental laboratory-associated incidents worldwide. METHODS: We analysed 1126 laboratory-associated incidents reported globally between 1900 and 2025, including laboratory-acquired infections, personnel exposures, and accidental pathogen releases. Fatality and laboratory-associated outbreak (≥5 cases) were modelled separately. Multivariate logistic regression, classification and regression tree, and random forest models assessed associations across pathogen, personnel, procedural, facility, and regional variables. Performance was evaluated using stratified 5-fold cross-validation. RESULTS: Eighty-one fatalities (7.2%) and 148 outbreaks (13.1%) were identified. Fatal outcomes were strongly associated with pathogen risk group and class, particularly prions (OR 189.9) and RG4 pathogens (OR 32.4). Inadequate inactivation and leaks in wastewater or aerosols contributed to both outcomes. Personnel type was influential: microbiologists and technicians were more often associated with fatalities, whereas clinicians, researchers, students, and routine laboratory workers were more often associated with outbreaks. Higher containment facilities were protective in regression models. Random forest showed the strongest discrimination (AUCs of 0.814 for death and 0.799 for outbreak). CONCLUSIONS: Mortality is primarily driven by pathogen virulence, whereas outbreaks reflect operational and contextual factors. Risk assessment frameworks should address severity and transmission as distinct but complementary domains.
OBJECTIVES: We evaluated 7-day all-cause mortality after COVID-19 vaccination in a large population-based cohort. METHODS: Using the Vaccine Integrated Platform of Lombardy Region (Italy), we compared mortality rates of...OBJECTIVES: We evaluated 7-day all-cause mortality after COVID-19 vaccination in a large population-based cohort. METHODS: Using the Vaccine Integrated Platform of Lombardy Region (Italy), we compared mortality rates of individuals who received a first vaccine dose between 27 December 2020 and 28 February 2022 with unvaccinated individuals, matched by sex, age, residence health district and Covid Vulnerability Score. The Cox regression model estimated the association between vaccination and 7-day mortality risk. Moreover, a modified self-controlled case series (SCCS) design allowed a within-person comparison of mortality rates between risk intervals (Days 0-7 after first dose, second dose, and booster dose) and the control interval outside vaccination. Mortality rate ratios (MRRs) and 95% CI were estimated. RESULTS: The cohort study included 7,612,244 exposed at least to the first vaccine dose, matched to as many controls. Overall, 717 and 3070 deaths occurred among vaccinated and controls, corresponding to mortality rates of 13.5 and 62.8 deaths per 1,000,000 person-days, respectively. Vaccination was associated with reduced 7-days mortality risk (HR: 0.21, 95% CI 0.19-0.23). The SCCS study included 127,122 all-cause deaths during the study period. MRRs after administration of first, second, and booster doses were 0.46 (95% CI 0.43-0.49), 0.53 (95% CI 0.50-0.57), and 0.61 (95% CI 0.57-0.65), respectively. CONCLUSIONS: Mortality rates were lower during the short-term interval following vaccine administration compared to unexposed periods. Our findings support the conclusion that the benefits of COVID-19 vaccination outweigh the risks, despite potential for serious adverse effects.
OBJECTIVES: This narrative review aims to aggregate all reports of nosocomial transmission of rare yeast species, to provide an overview of global trends, causative species, clinical characteristics and preventive measur...OBJECTIVES: This narrative review aims to aggregate all reports of nosocomial transmission of rare yeast species, to provide an overview of global trends, causative species, clinical characteristics and preventive measures. METHODS: A comprehensive literature search of multiple databases was conducted, to identify all reported nosocomial transmission events involving rare yeast species. The five most common yeasts, Candida albicans, Nakaseomyces glabratus, Candida parapsilosis, Candida tropicalis and Pichia kudriavzevii, in addition to Candida auris were excluded. RESULTS: A total of 76 reports were retrieved since 1984, caused by 28 different species. Wickerhamoyces anomalus was the most common agent, followed by Magnusiomyces, Trichosporon and species of the Candida haemulonii complex. Since the early 2000s, a clear increase was noted both in the number of outbreak reports and range of associated species, largely due to improved diagnostics. Most species were resistant to one or multiple antifungals and although environmental sampling was often performed, virtually all efforts yielded negative results. Once noted, strict hand hygiene practices and proper cleaning and disinfection of medical equipment has shown in curbing nosocomial spread. CONCLUSION: As hospital outbreak events are increasingly reported, accurate species identification and epidemiological surveillance should be in place for rapid detection. An enhanced focus on infection control measures was often sufficient to prevent new cases. Importantly, high-resolution genotyping is needed to confirm clonal transmission, which is often not conducted.
Chudasama DY, Nsonwu O, Pollington TM
… +10 more, Amin-Chowdhury Z, McCormick J, Henderson KL, Uwais L, Agnew E, Mazzella A, Charlett A, Jeyaratnam D, Brown CS, Hope R
BACKGROUND: Health inequalities in Escherichia coli bacteraemia are increasingly recognised, with disadvantaged and minority groups disproportionately affected. Understanding intersecting inequality factors will clarify...BACKGROUND: Health inequalities in Escherichia coli bacteraemia are increasingly recognised, with disadvantaged and minority groups disproportionately affected. Understanding intersecting inequality factors will clarify the poorly understood drivers of overall and resistant E. coli infections. METHODS: We retrospectively analysed English surveillance data (2018/19-2023/24) of E. coli bacteraemia and resistance. Multivariable logistic regression assessed healthcare- vs community-associated (HA vs CA) and resistant vs susceptible cases. FINDINGS: Between April 2018 and March 2024, 242,604 cases of E. coli bacteraemia were reported. Minority ethnic groups were disproportionately represented among patients aged <75 years, in both HA and CA categories. CA cases in females aged 30-44 were 2.7, 4.2, 4.4 and 4.0 times greater in Asian, Black, Mixed and Other ethnicities vs their White counterparts. Multivariable analysis showed odds of antibiotic resistant E. coli bacteraemia were more than twice that in the Asian (OR 2.45, p<0.0001), and 51.0% greater in the Black (p<0.0001) ethnicities, respectively, compared to their White counterparts. Odds of resistance amongst the Asian ethnic group was twice the national average for 2nd (37.2 vs 18.3%) and 3rd generation cephalosporins (35.2 vs 16.1%) and ciprofloxacin (37.1 vs 17.9%). Residing within a care home more than doubled the odds of resistant infection (OR 2.28, p<0.0001). CONCLUSIONS: Younger individuals of ethnic minorities particularly females experienced a disproportionate burden of infection, with resistance to key antibiotics particularly elevated in the Asian population. Care home residents had significantly higher rates of CA and resistant E. coli bacteraemia. Greater understanding of the source of infection in these groups is essential to inform targeted interventions.
OBJECTIVES: Aspergillosis is a fungal infection known to contribute to post-tuberculosis lung disease, but its prevalence and impact during tuberculosis (TB) treatment are not well understood. We aimed to estimate the pr...OBJECTIVES: Aspergillosis is a fungal infection known to contribute to post-tuberculosis lung disease, but its prevalence and impact during tuberculosis (TB) treatment are not well understood. We aimed to estimate the prevalence of Aspergillus infection among newly diagnosed TB patients and its association with treatment response and outcomes. METHODS: We conducted a prospective cohort study of pulmonary TB patients in Lima, Peru. We screened for Aspergillus infection by measuring anti-Aspergillus antibodies in serum at TB treatment initiation and after two months of treatment. We assessed patient disease status at baseline and two months with chest x-ray, the St. George's Respiratory Questionnaire (SGRQ), and 6-minute walking test. We used modified Poisson regression to identify risk factors for baseline Aspergillus seropositivity and study the association of Aspergillus seropositivity with clinical non-improvement at 2 months and with final treatment outcomes. RESULTS: At baseline, 5.4% of 1998 participants were seropositive for anti-Aspergillus antibodies. Older age and a history of prior TB were associated with baseline Aspergillus seropositivity. Cavitary lesions were not a significant risk factor for the presence of Aspergillus antibodies. The presence of baseline Aspergillus antibodies was found to be independently associated with non-improvement on chest x-ray (adjusted RR = 1.76, 95% CI: 1.07, 2.89) and non-improvement in SGRQ score (adjusted RR = 1.44, 95% CI: 1.02, 2.03) after 2 months. CONCLUSIONS: Aspergillus seropositivity was associated with poorer clinical response during TB treatment, including among patients with no prior history of TB. These findings raise the possibility that aspergillosis may emerge during TB treatment itself and underscore the importance of careful end-of-treatment and post-treatment monitoring to improve longer-term outcomes.
Smith CS, Mohmand Z, Hrycyshyn A
… +6 more, Djerboua M, Mann Y, Flemming JA, Gill SS, Bai AD, Queen’s University Internal Medicine Resident Research Initiative
BACKGROUND: People who inject drugs may be at risk for influenza due to comorbidities and social determinants of health. We aimed to determine if a history of injection drug use is a risk factor for severe influenza. MET...BACKGROUND: People who inject drugs may be at risk for influenza due to comorbidities and social determinants of health. We aimed to determine if a history of injection drug use is a risk factor for severe influenza. METHODS: We conducted a nested case-control study using the ICES (formerly Institute for Clinical Evaluative Sciences) database. Adults in Ontario, Canada were followed from July 1, 2022 to March 31, 2025. Cases consisted of adults admitted to hospital with severe influenza. Controls were adults who were not hospitalized for influenza. Each case was matched to 10 controls on age and sex. The exposure of injection drug use was determined based on a validated algorithm using hospitalization or emergency department visit diagnoses, physician billing codes, and opioid agonist treatment. A multivariable conditional logistic regression model was used to adjust for other known risk factors including sociodemographics, comorbidities, vaccination, and healthcare utilization. RESULTS: The study included 9514 cases and 95,140 matched controls. For both cases and controls, the median (interquartile) age was 74 (61-84) years and 53% were female. There were 559 (5.9%) cases and 1288 (1.4%) controls who had a history of injection drug use. In a multi-variable conditional logistic regression model, persons with a history of injection drug use had an adjusted odds ratio of 2.59 (95% CI 2.29-2.92, P<0.0001) of being hospitalized for influenza. CONCLUSIONS: People who inject drugs are at a substantial increased risk for severe influenza. Public health efforts including vaccination campaigns should be targeted towards this population.
BACKGROUND: Since SARS‑CoV‑2 became established in humans, children encounter it from early life, similar to seasonal human coronaviruses (hCoVs). To understand how SARS‑CoV‑2 compares to other hCoVs in early childhood,...BACKGROUND: Since SARS‑CoV‑2 became established in humans, children encounter it from early life, similar to seasonal human coronaviruses (hCoVs). To understand how SARS‑CoV‑2 compares to other hCoVs in early childhood, we measured infections and symptoms in an unvaccinated community cohort. METHODS: The VIOOL study follows healthy children under 4 years for 16 weeks during three winter seasons (2021-2024). A total of 228 participants provided weekly nasal swabs, regardless of symptoms, tested for betacoronaviruses SARS‑CoV‑2 and OC43, and alphacoronaviruses NL63 and 229E. Daily symptoms were recorded. Regression models, adjusting for age, co‑infections, and repeated measures, were used to compare clinical presentation across viruses. Cox models evaluated whether prior homotypic or heterotypic infections influenced subsequent infection risk. RESULTS: Across 3540 person‑weeks, we detected 78 infections with SARS‑CoV‑2, 149 with OC43, 39 with NL63, and seven with 229E (incidence 7.7/100 person‑weeks; 95% CI: 6.8-8.6). Acute Respiratory Illness occurred in similar proportions across viruses. Runny nose, coughing, wheezing, and fever were the most common symptoms, with no major differences in severity or episode length. Sequential infections were frequent (42%). Prior alphacoronavirus infection modestly reduced betacoronavirus infection risk. CONCLUSION: SARS-CoV-2 resembles other hCoVs in symptoms and severity. Cross-protection from heterotypic coronaviruses may depend on order of infections.