OBJECTIVES: We aimed to evaluate the effectiveness of TYPHIBEV®, which was introduced through a catch-up campaign and routine immunization in Nepal, in preventing blood culture-confirmed typhoid fever among children. MET...OBJECTIVES: We aimed to evaluate the effectiveness of TYPHIBEV®, which was introduced through a catch-up campaign and routine immunization in Nepal, in preventing blood culture-confirmed typhoid fever among children. METHODS: We conducted a test-negative, case-control study where typhoid test-positive cases were defined as vaccine-eligible pediatric patients who tested positive for Salmonella Typhi by blood culture at participating health facilities and test-negative controls were vaccine-eligible patients who tested negative for S. Typhi on blood cultures. We matched by age, location, date of blood culture, and surveillance site. We used conditional logistic regression to calculate odds ratios(OR), and vaccine effectiveness was calculated as 1-OR. RESULTS: Between October 1, 2022 and December 31, 2024, 40 typhoid cases and 113 matched, test-negative controls were enrolled. Both cases and controls were similar in sociodemographic characteristics and water, sanitation and hygiene-related living conditions. Among 39 cases and 108 controls with known vaccine status, 20 cases (51%) and 91 controls (84%) had received TCV. Vaccine effectiveness was 89% (95% CI: 65-97%) and was lower among children <5 years (72%, 95% CI: -203-97%) compared with those 5-15 years (98%, 95% CI: 80-100%). Vaccine effectiveness estimates did not significantly differ when restricted to participants with documented vaccination status. CONCLUSIONS: The findings indicate that TYPHIBEV® was highly effective in preventing typhoid fever over a 30-month follow-up period following national introduction, with effectiveness estimates comparable to those observed for Typbar-TCV®.
Zhang H, Kang Z, Zhang Y
… +18 more, Yang Y, Li H, Wang N, Wang J, Jiao F, Tong S, Wang B, Gao S, Ni C, Shi X, Wu S, Huang S, Bao D, He Q, Wang C, Ruan Z, Fu P, Yang C
OBJECTIVES: A global resurgence of pertussis has followed the COVID-19 pandemic, yet the underlying drivers remain unclear. We investigated the contribution of Bordetella pertussis genomic evolution to the post-pandemic...OBJECTIVES: A global resurgence of pertussis has followed the COVID-19 pandemic, yet the underlying drivers remain unclear. We investigated the contribution of Bordetella pertussis genomic evolution to the post-pandemic resurgence. METHODS: We analyzed 8117 B. pertussis genomes from 35 countries, including 249 newly sequenced isolates collected from six regions in China. Temporal dynamics of genotypes, antigenic profiles, and macrolide resistance were examined before, during, and after the pandemic. RESULTS: Shared post-pandemic evolutionary patterns were identified across global B. pertussis populations. These included the emergence of macrolide-resistant strains in France, the United States, and Australia, and their dominance in eastern China, driven by the expansion of the MR-MT28 sublineage (ptxP3/fim3-1/prn150 or PRN-deficient). Parallel antigenic shifts were observed, with declining PRN-deficient strains accompanied by increasing prn2 allele frequencies in multiple regions. Region-specific dynamics were also evident. In China, the post-pandemic resurgence was characterized by near-complete replacement of circulating strains by the MR-MT28 sublineage. In contrast, the resurgence in Europe and the United States largely reflected the persistence and expansion of locally established lineages. Expanded sampling further revealed that MR-MT28 sublineage is no longer genetically homogeneous, having diversified into multiple phylogenetic groups, with most isolates detected outside China (72%, 8/11) being PRN-deficient. CONCLUSIONS: This unified global genomic analysis demonstrates both shared and region-specific post-pandemic shifts in B. pertussis populations. The dominance of the MR-MT28 sublineage in China, together with its international dissemination and ongoing diversification, represents a growing public health concern and underscores the need for coordinated global genomic surveillance.
OBJECTIVE: This scoping review aims to evaluate the application of environmental DNA/RNA (eNA) technology in real-world studies on neglected tropical diseases (NTDs), assessing its methodology and detection effectiveness...OBJECTIVE: This scoping review aims to evaluate the application of environmental DNA/RNA (eNA) technology in real-world studies on neglected tropical diseases (NTDs), assessing its methodology and detection effectiveness, and providing an evidence-based roadmap for optimizing eNA used to support progress toward the 2030 targets. BACKGROUND: As the NTDs roadmap reaches its midpoint, eNA technology has seen increasing adoption. This non-invasive approach enables qualitative/quantitative assessment of environmental transmission risks, complementing conventional detection methods. METHODS: We synthesized real-world field applications of eNA technology across NTDs through systematic searches in four English, and one Chinese database (2002-2024). A total of 71 studies met our inclusion criteria after screening. RESULTS: Despite heterogeneous transmission mechanisms among NTDs, we identified 6 standardized field applications for eNA studies, along with practical optimization strategies. A total of 3 pathways were concluded of how eNA technology can accelerate the NTDs elimination. For the performance, comparative analyses showed moderate concordance with conventional methods, while eNA demonstrated superior sensitivity in detection of pathogens and hosts. With the gap analysis, we demonstrated the advances of eNA applications in all NTDs. CONCLUSIONS: This scoping review supports eNA technology as a promising tool for NTDs detection and surveillance. Through experience sharing and summarization, the eNA technology needs further optimization and standardization to enhance its disease surveillance capacity, thereby accelerating the achievement of NTDs roadmap targets.
Suda G, Ohara M, Baba M
… +26 more, Yamamoto Y, Yoshida S, Fu Q, Yang Z, Hosono H, Yokoyama D, Kitano S, Tanaka T, Meno A, Yasuura N, Kitagataya T, Kawagishi N, Nakai M, Sho T, Ogawa K, Maehara O, Ohnishi S, Izumi T, Yamada R, Meguro T, Terashita K, Takagi T, Ito J, Kobayashi T, Tsunematsu I, Sakamoto N
OBJECTIVE: Our prior interim report remains the only prospective study evaluating tenofovir alafenamide (TAF) for HBV reactivation prevention, with prophylaxis assessed up to 12 months. Herein, we report the final 24-mon...OBJECTIVE: Our prior interim report remains the only prospective study evaluating tenofovir alafenamide (TAF) for HBV reactivation prevention, with prophylaxis assessed up to 12 months. Herein, we report the final 24-month follow-up results. METHODS: This multicentre prospective-study enrolled HBV carriers who received prophylactic TAF before antineoplastic or immunosuppressive therapy and patients with resolved HBV infection who developed reactivation and received TAF as reactivation-related hepatitis prophylaxis. We examined TAF effectiveness at 12 and 24 months. The primary endpoints were HBV reactivation and reactivation-related hepatitis. RESULTS: Of 191 enrolled patients, 150 and 127 were evaluable at 12 and 24 months, respectively. At 12 months, no HBV reactivation, HBV reactivation-related hepatitis, or therapy interruption occurred. Between months 12-24, four patients discontinued TAF. None of the remaining patients experienced HBV reactivation, HBV reactivation-related-hepatitis, or treatment interruption. Virologic relapse occurred in one of two patients with TAF discontinuation after anticancer/immunosuppressive therapy completion; TAF re-initiation enabled biochemical hepatitis prevention and viral suppression. Neither patient who switched to entecavir experienced reactivation. No patients on high-risk regimens developed reactivation, reactivation-related hepatitis, or treatment interruption. No patient discontinued therapy for TAF-related adverse events. CONCLUSIONS: Over 24 months, TAF demonstrated effectiveness in preventing HBV reactivation and reactivation-related hepatitis.
OBJECTIVES: Pertussis has witnessed a resurgence in morbidity in recent years. In most countries, pertussis surveillance is inadequate for accurately estimating numbers of cases or deaths. The study aimed to identify the...OBJECTIVES: Pertussis has witnessed a resurgence in morbidity in recent years. In most countries, pertussis surveillance is inadequate for accurately estimating numbers of cases or deaths. The study aimed to identify the true burden of pertussis based on the published seroepidemiology studies of pertussis worldwide. METHODS: A systematic search of five databases was conducted to identify relevant population-based studies published between January 1, 2013, and December 31, 2024. The seroprevalence and sero-incidence of anti-pertussis (anti-PT) IgG antibodies were extracted and the estimated incidence of Bordetella pertussis (B. pertussis) infection was calculated based on the meaning of the cut-off value of anti-PT IgG with meta-analysis. The estimated case numbers and incidence of B. pertussis infection across WHO regions were calculated and compared with the data from Global Burden of Disease (GBD) and Global Health Observatory (GHO). RESULTS: Totally 164 articles were eligible for inclusion in our systematic review and meta-analysis after screening. Overall, the global seroprevalence of pertussis anti-PT IgG antibodies was 23.39% (95% CI 12.63-39.20%) during 2010-2023 and the estimated incidence of B. pertussis infection was 5.11% (95% CI 2.97-8.63%). Compared with regions using whole-cell pertussis (wP) vaccines (24.63%), those predominantly employing acellular pertussis (aP) vaccines demonstrated a higher seroprevalence (26.39%) but lower estimated infection rates (aP: 4.23% vs. wP: 6.15%; P<0.001). Subgroup analysis showed that the seroprevalence of pertussis anti-PT IgG antibodies in different age groups ranged from 16.72% to 56.27%, while the estimated incidence of B. pertussis infection ranged from 3.84% to 13.75%. The World Health Organization African Region contributed the highest seroprevalence of pertussis anti-PT IgG antibodies at 46.28%, while the World Health Organization American Region had the highest incidence of B. pertussis infection at 13.46%. It is estimated that annual pertussis cases can reach 386 million and the incidence of pertussis is much higher than the reported data from GHO and the estimated data from GBD. CONCLUSIONS: The true burden of pertussis has likely been grossly underestimated, with its incidence potentially much higher than currently recognized.
Ordóñez-Mena JM, Radin JM, Hoang U
… +22 more, Araujo AB, Balogh O, Eltayeb A, Jamie G, Elson WH, Lu T, Gu X, Batool F, Madia J, Fan X, Byford R, Enesca E, Button E, Martin D, Ferreira F, Hoschler K, Kele B, Cogdale J, Talts T, Sebastian-Pillai P, Zambon M, de Lusignan S
OBJECTIVES: To describe the positivity, clinical presentation and predictors of respiratory syncytial virus (RSV) in adult primary care patients compared to influenza and SARS-CoV-2, prior to the introduction of RSV vacc...OBJECTIVES: To describe the positivity, clinical presentation and predictors of respiratory syncytial virus (RSV) in adult primary care patients compared to influenza and SARS-CoV-2, prior to the introduction of RSV vaccines. METHODS: We analyzed data from primary care patients aged ≥40 years with an acute respiratory infection. Between 02/10/2023 and 10/04/2024 virology swabs were tested by the UK Health Security Agency for RSV, influenza A and B, and SARS-CoV-2. Percent positivity with 95% confidence intervals (CIs) were estimated. Multivariable logistic regression identified predictors of infection. Clinical presentations were described and compared. RESULTS: Among 6,161 individuals tested, influenza A had the highest positivity (3.25%, 95% CI: 2.83-3.72), followed by SARS-CoV-2 (2.30%, 95% CI: 1.96-2.71), RSV (2.26%, 95% CI: 1.91-2.66), and influenza B (0.28%, 95% CI: 0.17-0.44). RSV positivity was higher in people aged 60-74 compared to those aged 40-49. RSV cases presented with ILI less often than COVID or influenza A cases. CONCLUSIONS: During the 2023/24 winter season in England, medically-attended RSV presented a significant disease burden, with a positivity comparable to SARS-CoV-2 and approximately 70% of influenza. Given well-established vaccination programmes for influenza and COVID-19, these findings demonstrate an opportunity to introduce an RSV vaccination programme for adults.
OBJECTIVES: Neisseria meningitidis is a major pathogen of septicemia and meningitis, with a fatality rate of 10%-15%. Cefotaxime resistance in N. meningitidis remains rare, and has not yet been reported in internationall...OBJECTIVES: Neisseria meningitidis is a major pathogen of septicemia and meningitis, with a fatality rate of 10%-15%. Cefotaxime resistance in N. meningitidis remains rare, and has not yet been reported in internationally disseminated serogroup Y (MenY) ST-23 clonal complex (cc23) strains. This study aimed to characterize the molecular epidemiology of a novel cefotaxime- and ciprofloxacin-resistant MenY cc23 clone. METHODS: During the period of 2023-2025, 10 MenY isolates were collected from patient (n=1), close contact (n=8), and carrier (n=1) in Shanxi, China. The minimum inhibitory concentrations (MICs) of 12 antibiotics were determined by MIC test strip. Whole genome sequencing (WGS) was performed to analyze molecular types, resistance mechanisms, and phylogenetic relationships with other cc23 isolates globally. RESULTS: Among the 10 MenY isolates, seven were resistant to both cefotaxime (MIC range, 0.75-1 μg/ml) and ciprofloxacin (0.125 μg/ml), intermediate to penicillin (0.19-0.38 μg/ml), and susceptible to ceftriaxone (0.125 μg/ml). These seven isolates shared the fine type Y: P1.5-1,10-1: F4-1: ST-18108 (cc23). WGS analysis revealed that the ST-18108 isolates harbored NEIS1753 allele 5058 (with PBP2 mutations A311V, I312M, V316P, T483S, N512Y, and G545S) and gyrA92 allele (GyrA mutation T91I). NEIS1753_5058 allele phylogenetically clustered with alleles found in N. meningitidis, N. lactamica, and N. cinerea isolates. The nine ST-18108 genomes from this study (n=7) and a previous report from Hebei province (n=2) formed a closely related cluster within the sublineage L23.1, sharing 175 unique single nucleotide polymorphisms (SNPs). CONCLUSIONS: A novel cefotaxime- and ciprofloxacin-resistant MenY cc23 clone has emerged in China, with an enhanced transmissibility and a higher level of cefotaxime-resistance, potentially challenging the current IMD treatment and chemoprophylaxis strategies across broader geographic regions. Continuous surveillance for this dual-resistant clone is warranted, utilizing molecular markers including ST-18108, NEIS1753_5058 allele, and the 175 SNPs identified in this study.
OBJECTIVES: Hypervirulent Klebsiella pneumoniae (hvKp) ST23-K1 poses a global health threat due to its high virulence and increasing antimicrobial resistance. This study aimed to characterise the genomic feature and phyl...OBJECTIVES: Hypervirulent Klebsiella pneumoniae (hvKp) ST23-K1 poses a global health threat due to its high virulence and increasing antimicrobial resistance. This study aimed to characterise the genomic feature and phylogenetic evolution of ST23-K1 in China. METHODS: K1 isolates from a nationwide epidemiological surveillance project underwent whole-genome sequencing. Virulence was assessed using hypermucoviscosity phenotyping and a murine infection model. For ST23-K1 carrying acquired antimicrobial resistance genes (ARGs), the CRISPR/Cas system, protospacers, anti-CRISPR (Acr) genes, and plasmidome were characterised. Time-resolved phylogenetic analysis was performed using integrated locally generated and publicly available data. RESULTS: Among 400 K1 isolates, ST23 was the most prevalent sequence type, and its effective population size increased following CG23-I divergence. The CG23-I sub-lineage was widely distributed nationwide with limited evidence of clonal transmission. Isolates with an incomplete cps locus exhibited significantly reduced virulence compared with those carrying an intact locus. The prevalence of extended-spectrum β-lactamase-positive ST23-K1 isolates increased over time, whereas carbapenemase-producing isolates remained stable. Among acquired ARGs-positive ST23-K1 isolates, a conserved protospacer corresponding to a prevalent spacer was identified. This protospacer, together with AcrIE genes, was frequently co-located on IncFII-type plasmids. CONCLUSION: ST23-K1 remains a hypervirulent lineage undergoing ongoing evolutionary expansion. The presence of acquired ARGs in ST23-K1 may be associated with AcrIE-harbouring IncFII plasmids, and functional validation is required to clarify the underlying mechanisms. Continuous genomic surveillance is essential to monitor the evolution and antimicrobial resistance trends of ST23-K1.
D'Abramo A, Colavita F, Ponzetta L
… +18 more, De Marco P, Vita S, Rosa L, Cammisa S, Tartaglia E, Scorzolini L, Lalle E, Cimini E, Notari S, Tiberi M, Grifoni A, Weiskopf D, Sette A, Petrone L, Maggi F, Goletti D, Nicastri E, DENGVAC study group
OBJECTIVES: This study was designed to assess the safety and immunogenicity of the first dose of the TAK-003 dengue vaccine. The immune response profiles of vaccinated participants were compared among individuals who exp...OBJECTIVES: This study was designed to assess the safety and immunogenicity of the first dose of the TAK-003 dengue vaccine. The immune response profiles of vaccinated participants were compared among individuals who experienced or did not experience natural dengue infection in the past or as an acute infection. METHODS: In this single-centre prospective observational study, subjects were stratified into three groups: Group1-dengue seronegative; Group2-dengue seropositive; Group3-acute dengue infection. The assessments of vaccine-induced immunogenicity included: DENV-2 neutralizing antibodies, monocyte and dendritic cell (DC) phenotyping and T-cell response at baseline (T0) and 3 months (T3) post-vaccination (Group1 and 2) or post-infection (Group3). RESULTS: One hundred fifty subjects were enrolled at T0, and among them 80 subjects (median age 38 years, 50% male) were also evaluated at T3. Anti-DENV-2 neutralizing antibodies increased 26.9- and 9.19-fold in Group1 and 2, and 3.06-fold in Group3. Group1 showed increased monocytes and Group3 had reduced myeloid-DC and higher plasmacytoid-DC. Group1 and 2 exhibited DENV CD4 MP-induced T-cell responses similar to those observed in Group3. Notably, Group1 demonstrated a significantly greater T-cell response to the DENV CD8 MP than Group3. CONCLUSIONS: Preliminary data showed that TAK-003 vaccine is safe and immunogenic. The first vaccine dose elicits a functional antibody and a robust T-cell response. Further analyses on the current cohort are ongoing.
Malassezia are lipid-dependent commensal yeasts and an uncommon cause of invasive fungal infection. These are likely underreported due to the specific requirements for Malassezia growth, and therefore poorly understood....Malassezia are lipid-dependent commensal yeasts and an uncommon cause of invasive fungal infection. These are likely underreported due to the specific requirements for Malassezia growth, and therefore poorly understood. This review compiles all cases of invasive Malassezia infection published to date and depicts the main features of these infections. A literature search was conducted using PubMed up to December 2024. 803 records were found, of which 167 cases were analyzed. The review highlights the epidemiology and predisposing factors, with premature newborns, digestive diseases, and lipid supplementation being the main. Further studies are needed to evaluate the usefulness of molecular techniques for detecting Malassezia in blood and tissues. The review suggests a shift in the causative species related to more reliable identification systems. While being the most frequently used antifungal drug, there is little evidence that intravenous amphotericin B is the most appropriate treatment.
OBJECTIVES: To assess amikacin target attainment in patients with a haematological disorder treated for febrile neutropenia or severe infection and to develop a population pharmacokinetic (PK) model. METHODS: This prospe...OBJECTIVES: To assess amikacin target attainment in patients with a haematological disorder treated for febrile neutropenia or severe infection and to develop a population pharmacokinetic (PK) model. METHODS: This prospective observational single-centre study was conducted at the University Hospital Basel, Switzerland between December 2022 and February 2024. Adult patients with a haematological disorder treated with amikacin for 1-3 days were included. Total amikacin concentrations in blood were measured 1 h and 8 h after each administration. The primary objective was target attainment (C ≥60 mg/L) at all time points evaluated (in the context of the amikacin ECOFF of 8 mg/L for Enterobacterales). A population PK model was developed to derive individual exposure estimates. RESULTS: Overall, 57 patients with 119 amikacin applications and 174 concentration measurements were included. The median age was 61 years [interquartile range (IQR) 53-68] and 33% were female. Targets of C ≥60 mg/L were attained in 11/57 patients (19.3%) and C/MIC≥8 in 10/10 patients (100%), in whom a pathogen was identified. In the population PK model, weight and GFR were correlated with PK parameters in the multivariable analysis. CONCLUSIONS: Amikacin target attainment was low in patients with a haematological malignancy treated empirically for FN, when pathogens with higher MICs are considered. Dosing optimisation may be needed to improve target attainment.
OBJECTIVES: Despite the decline in HBV and HCV incidence in Italy, identifying at-risk populations remains a priority. We aimed to identify risk profiles for acute HBV and HCV infections and possible signals of reporting...OBJECTIVES: Despite the decline in HBV and HCV incidence in Italy, identifying at-risk populations remains a priority. We aimed to identify risk profiles for acute HBV and HCV infections and possible signals of reporting disproportionality. METHODS: The study used data from the Integrated Epidemiological System of Acute Viral Hepatitis from 2004 to 2024. K-medoids clustering was applied to identify acute hepatitis profiles, considering demographic characteristics and major risk factors (drug use, nosocomial risk, men who have sex with men - MSM, risky sexual behaviour, living with HBsAg+ person). Disproportionality signals were assessed using reporting odds ratio (ROR) and 95% confidence intervals (95%CI). RESULTS: The 3339 HBV cases were divided into 9 profiles. The most common profiles included Italian males: without reported risk factors (n=940, 28.2%), with heterosexual (n=719, 21.5%), or MSM (n=315, 9.4%) risk sexual behaviour. Six signals for HBV were identified, the most recent for females living with HBsAg+ person (2023 ROR=2.8, 95%CI=1.4-5.6) or without reported risk factors (2021 ROR=2.4, 95%CI=1.5-8.1). The 975 HCV cases were divided into 8 profiles, the most frequent consisting of predominantly Italian females with no reported risk factors (n=181, 18.6%) and young Italian males with a history of drug use (n=135, 13.8%). There were 11 signals identified for HCV of which 5 related to the MSM profile with risky sexual behaviour (most recent in 2024: ROR=4.0, 95%CI=1.5-10.3). CONCLUSIONS: Acute HBV and HCV infections are frequently reported in individuals lacking commonly known risk factors. Awareness and screening campaigns aimed also at low-prevalence populations are needed to reach the elimination target of viral hepatitis as a public health problem.
van Beek LF, Comans SET, Totté K
… +11 more, Fröberg J, van der Gaast-de Jongh CE, Eleveld M, Ferreira DM, Verweij JJ, Murk JL, McCall MBB, Mordmüller B, de Graaf H, de Jonge MI, Diavatopoulos DA
OBJECTIVES: Colonisation of the upper airways by Streptococcus pneumoniae is a prerequisite for disease development and shapes immune responses that vary between geographical settings. This first controlled human pneumoc...OBJECTIVES: Colonisation of the upper airways by Streptococcus pneumoniae is a prerequisite for disease development and shapes immune responses that vary between geographical settings. This first controlled human pneumococcal infection study in the Netherlands assessed colonisation, antibody responses, respiratory symptoms, and concurrent viral infections. METHODS: Twenty healthy adults (19-47 years) were enrolled between May 2022 and February 2023 and inoculated intranasally with 160,000 colony forming units of S. pneumoniae serotype 6B (strain BHN418). Participants were monitored for 28 days to assess colonisation, respiratory viral infection and safety. Serum and nasal lining fluid were collected to measure IgA, IgM and IgG responses to serotype 6B polysaccharide (6B) and whole pneumococci. RESULTS: Eight of 20 participants (40%) became colonised. Colonised participants showed significant rises in serum and mucosal IgG and IgA to 6B, but not to pneumococci. Fifteen participants tested positive for at least one respiratory virus. Symptoms were generally mild but occurred more often in those with concurrent pneumococcal colonisation and viral infection. CONCLUSIONS: Colonisation rates were comparable to studies in other populations. Colonisation induced systemic and mucosal antibody responses, while viral co-infection increased symptom burden. This controlled infection study demonstrates feasibility and safety, and establishes a platform for vaccine evaluation and pneumococcal-viral interaction studies.
BACKGROUND: Tuberculosis (TB) remains a major global health threat. ANKRD22 has emerged as a candidate biomarker from transcriptomic studies, but its diagnostic and functional role in TB is unclear. METHODS: We analyzed...BACKGROUND: Tuberculosis (TB) remains a major global health threat. ANKRD22 has emerged as a candidate biomarker from transcriptomic studies, but its diagnostic and functional role in TB is unclear. METHODS: We analyzed 23 public transcriptomic datasets and validated results in a clinical cohort. ANKRD22 expression was measured by RT‑qPCR. Diagnostic performance was evaluated using ROC analysis. Immune correlations were investigated via GO, KEGG, GSEA, and immune deconvolution. In vitro studies used H37Ra‑infected THP‑1 macrophages with ANKRD22 knockdown. RESULTS: ANKRD22 expression was significantly upregulated in TB disease compared to infected individuals and healthy controls, increased progressively along the disease continuum, and declined following effective anti‑TB treatment. It demonstrated strong diagnostic performance across multiple datasets (AUC range: 0.709-0.986) and in clinical samples (AUC = 0.855). High ANKRD22 expression was positively correlated with MLR and associated with an immunosuppressive microenvironment characterized by increased infiltration of neutrophils, mast cells, regulatory T cells, and myeloid‑derived suppressor cells, alongside decreased NK cells. In vitro, ANKRD22 knockdown attenuated M2 macrophage polarization. CONCLUSION: ANKRD22 is a promising diagnostic biomarker for active TB and is linked to an immunosuppressive immune microenvironment, supporting its potential for diagnosis and host‑directed therapy.
Osman S, Science M, McLachlan E
… +12 more, Severini A, Arnold C, Petel D, Hatchette T, Deeks S, Halperin SA, Wright J, Brown K, Richardson S, Campigotto A, Crowcroft N, Bolotin S
OBJECTIVES: Measles is a highly infectious virus with potentially serious complications. Infants too young to be vaccinated depend on maternally-derived, transplacentally-transferred antibodies for early protection. We a...OBJECTIVES: Measles is a highly infectious virus with potentially serious complications. Infants too young to be vaccinated depend on maternally-derived, transplacentally-transferred antibodies for early protection. We aimed to identify factors influencing maternal measles immunity, and determine predictors of maternal susceptibility and infant immunity during the first year of life. METHODS: Using a prospective cross-sectional study design, we collected data and samples from infant-mother pairs admitted to the Hospital for Sick Children between 2018 and 2020. Measles antibody titres were measured using the gold-standard plaque reduction neutralisation test. RESULTS: We recruited 258 mothers aged 16-45 years, of whom 80.6% (95% CI: 75.8,85.4) had protective antibody levels. The proportion with protective antibodies was lowest among mothers <25 years at 67.9% (95% CI: 50.6,85.2), increasing to 100% (95% CI: 100.0,100.0) in those >40 years. Among the 233 individuals reporting vaccination status, 97.0% received at least one measles-containing vaccine. CONCLUSIONS: Nearly one-fifth of mothers in our study were seronegative to measles, increasing to nearly one-third of mothers under 30 years. The higher susceptibility observed in younger individuals within a highly-vaccinated cohort may suggest waning humoral immunity. Further research is needed to understand the significance of the high proportion of seronegative individuals in younger age groups.
Zhou T, Zhang B, Zhang D
… +21 more, Jhaveri R, Chen J, Becich MJ, Castro L, Chen Y, Chilukuri N, Herring SJ, Lei Y, Li L, Lu Y, Hornig M, Khalsa AS, Liebovitz D, Mosa ASM, Taylor BW, Tedla YG, Thodeson D, Tong J, Wu Q, Forrest CB, Chen Y
OBJECTIVES: Post-acute sequelae of SARS-CoV-2 infection (PASC) can affect multiple organ systems, but the role of preinfectional body mass index (BMI) in these outcomes among children and young adults remains unclear. We...OBJECTIVES: Post-acute sequelae of SARS-CoV-2 infection (PASC) can affect multiple organ systems, but the role of preinfectional body mass index (BMI) in these outcomes among children and young adults remains unclear. We aimed to evaluate the association between pre-COVID-19 BMI status and post-acute cardiovascular, gastrointestinal, and neuropsychiatric outcomes in children and young adults. METHODS: We conducted a retrospective cohort study using data from 139,320 individuals aged 5 to 20 years with confirmed SARS-CoV-2 infection between March 2020 and September 2023 across 20 U.S. pediatric health systems participating in the RECOVER Initiative. Pre-infection BMI was defined using measurements obtained within 18 months before the index date and categorized as healthy weight, overweight, obesity, or severe obesity; when multiple values were available, the most recent measurement was selected. We assessed incident post-acute cardiovascular, gastrointestinal, and neuropsychiatric symptoms and conditions occurring 28 to 179 days post-infection. Adjusted relative risks (RRs) were estimated using modified Poisson regression models, comparing elevated BMI categories to the healthy weight. FINDINGS: Among 139,320 participants (mean [SD] age, 13.0 [4.3] years; 51.6% female), severe obesity was associated with a higher risk of cardiovascular disorders (adjusted RR 2.56; 95% CI 1.93-3.41), particularly hypertension (adjusted RR 3.68; 95% CI 2.65-5.11). Severe obesity was also linked with increased risks of diarrhea (adjusted RR 1.34; 95% CI 1.10-1.64) and gastroesophageal reflux disease (adjusted RR 1.29; 95% CI 1.06-1.58). Associations between BMI and neuropsychiatric outcomes were heterogeneous, with inverse associations observed for some conditions, including anxiety and major depression. INTERPRETATION: In this cohort study, pre-COVID-19 BMI status was associated with the risk and pattern of post-acute cardiovascular and gastrointestinal outcomes among children and young adults. Association between pre-infection BMI and neuropsychiatric outcomes was more variable and should be interpreted with caution. These findings suggest BMI-stratified post-COVID-19 monitoring strategies may help inform long-term care in youth.