Importance:The optimal choice of antibiotic prophylaxis in elective colorectal surgery remains uncertain, with most reviews emphasizing timing and route of administration rather than direct comparisons of antibiotic classes. Objective:To compare the outcomes associated with different antibiotic classes and class combinations administered within 24 hours before elective colorectal surgery. Data Sources:MEDLINE, Embase, Cochrane Central, and Scopus were searched from inception to July 17, 2025. Study Selection:Eligible studies were randomized clinical trials that enrolled adult patients undergoing elective colorectal procedures and were required to report on surgical site infection (SSI) within 30 days of surgery. Data Extraction and Synthesis:Data on SSIs, adverse events, all-cause mortality, and length of hospital stay were extracted when available by 2 independent reviewers. A frequentist random-effects model was used for network meta-analysis. Reporting followed the Preferred Reporting Items for Systematic Review and Meta-Analyses, Extension Statement for Reporting of Systematic Reviews Incorporating Network Meta-Analyses of Health Care Interventions. Main Outcomes and Measures:The primary outcome was risk of SSI; secondary outcomes were 30-day mortality, adverse events, and length of hospital stay. Risk ratios (RRs) with 95% CIs were calculated for binary outcomes, and mean differences (MDs) with SDs were calculated for continuous outcomes. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Findings:A total of 105 randomized clinical trials involving 18 273 patients were included. The network included 32 distinct antibiotic nodes defined by antimicrobial class or combination. High to moderate certainty of evidence indicated that, compared with placebo or no antibiotic, several regimens were associated with reduced the risk of SSI. Regimens including broad-spectrum penicillin (RR, 0.26; 95% CI, 0.16-0.42), third-generation cephalosporins (RR, 0.27; 95% CI, 0.16-0.45), a combination of metronidazole and second-generation cephalosporins (RR, 0.27; 95% CI, 0.17-0.44), and tetracyclines (RR, 0.32; 95% CI, 0.20-0.53) were all associated with significant reductions. The antibiotics associated with a significant decrease in mortality compared with placebo were broad-spectrum penicillin (RR, 0.21; 95% CI, 0.05-0.90) and a combination of fluoroquinolones and penicillins (RR, 0.14; 95% CI, 0.03-0.79). No significant differences were observed between antibiotic classes regarding hospital length of stay or adverse events. The certainty of evidence ranged from very low to moderate across outcomes. Conclusions and Relevance:In this systematic review and network meta-analysis, several antibiotic regimens were associated with substantially reduced risk of SSIs after elective colorectal surgery compared with placebo. Broad-spectrum penicillins had the most consistent benefits, with moderate-certainty evidence supporting reductions in risk of both SSI and mortality.

Background Despite being widely used in other fields, composite outcomes are seldom used in influenza vaccine randomized trials. Vaccine trialists may benefit from the increased event rates and power of composite outcomes. We explored the use of a composite outcome on a series of randomized control trials conducted within Canadian Hutterite communities. Methods Using data from three blinded, cluster randomized control trials of pediatric influenza vaccination, we assessed the use of a composite outcome of antimicrobial prescription, school or work-related absenteeism, and medically attended visits for respiratory illness. Key comparisons between component outcomes and the composite included odds reduction, frequency, and confidence intervals. Results In Trial 1, 65 Hutterite colonies were randomly assigned to receive either the influenza vaccine or the hepatitis A vaccine. Among all season 1 and 3 participants in Trial 1, the composite outcome yielded a greater event rate, significance, precision, and a greater protective effect than its components. Within participants across all seasons in Trial 2, the composite yielded a greater event rate, lower significance, a null protective effect, and greater precision than two out of three of its components. Among all participants across all seasons in Trial 3, the composite outcome yielded a greater event rate and a weaker protective effect than its components, with no notable differences in precision or significance. Conclusions Composite outcomes can be a viable approach to raise event rates and increase the precision of estimates in influenza vaccine trials and should be explored further within this field.

While Lyme disease (LD) is the most common tick-borne disease reported to public health surveillance in North America and is increasingly recognized as a public health threat in Canada, it's incidence may be underreported. Our study aims to estimate medically-attended LD incidence in Manitoba, Canada, using administrative health data. We identified medically-attended LD cases in Manitoba from 2010 - 2021 in a claims database (Manitoba Population Research Data Repository), which contains the health records of >95% of the residents of Manitoba, using diagnostic codes, antibiotic dispensations, and laboratory results. The incidence of claims-based LD cases ranged from 8.4 to 28.5 per 100,000 population per year, 5.1 to 11.0 times higher than the incidence of surveillance-reported LD cases. The incidence of claims-based LD cases was particularly higher than the incidence of surveillance-reported LD cases in females and health regions with a low surveillance-reported incidence. Our study suggests that medically attended LD is more common than reported in surveillance. Further study is required to identify barriers to reporting. Interventions are needed to reduce the substantial burden of LD in Manitoba.

BACKGROUND:Influenza transmission is influenced by both individual characteristics and community-level drivers. Understanding how these drivers jointly influence transmission is important to predicting outbreaks and guiding influenza prevention strategies. Our study aimed to assess individual and colony-level influences, including vaccination and environmental factors, on influenza transmission in the Hutterite communities. METHODS:We analyzed data from 3271 individuals in 46 Canadian Hutterite colonies during the 2008 influenza season. Weekly PCR-confirmed Influenza A and B outcomes were examined in relation to demographic, vaccination, geographic, and weather variables using multilevel Bayesian hierarchical models in Integrated Nested Laplace Approximations (INLA), which accounted for colony clustering and temporal autocorrelation. RESULTS:Of the 3271 participants, 239 (7.3%) had PCR-confirmed influenza (128 Influenza A and 111 Influenza B cases). Older age was found to be protective, especially for Influenza B, while males had slightly lower odds than females. Individual vaccination showed little effect, while colony assignment to influenza vaccination was associated with a lower risk of Influenza A and overall Influenza (A/B). Higher weekly mean temperatures were associated with lower odds of Influenza A but with higher odds of Influenza B. Precipitation showed weak associations, and geographic factors such as elevation and distance to the nearest city suggested possible protective effects, but results were imprecise. CONCLUSIONS:Our findings suggest that influenza risk in Hutterite colonies is associated with local environmental and geographic characteristics in addition to the individual drivers. Incorporating the community-level environmental setting in influenza surveillance may improve preparedness for future outbreaks.

Background: Group A streptococcal (GAS) pharyngitis drives substantial antibiotic prescribing in children. The 10-day standard burdens adherence and prolongs exposure, increasing selective pressure for resistance. Yet, whether shorter courses achieve comparable outcomes remains unresolved. Purpose: To address how the duration of oral antibiotics affects clinical outcomes in children and adolescents with suspected or confirmed GAS pharyngitis. Data Sources: MEDLINE, Embase, CENTRAL, Web of Science, and CINAHL from inception to July 2025. Reviewers also searched reference lists of eligible trials and relevant systematic reviews. Study Selection: Randomized trials enrolling children and adolescents ≤18 years with suspected or confirmed GAS pharyngitis comparing different durations of oral antibiotics, or oral antibiotics against placebo or no treatment. Data Extraction: Paired reviewers independently screened records, extracted data, and assessed risk of bias. Data Synthesis: We performed random-effects dose-response meta-analyses with restricted cubic splines and rated the certainty of evidence using GRADE. Forty-five trials enrolling 22,636 participants met eligibility criteria. Across outcomes, low to moderate certainty evidence suggests that 3, 5, and 10 days of antibiotic treatment may produce little to no difference. Moderate certainty evidence supports similar effects of 5 and 10 days on clinical cure, relapse, and adverse events. Evidence comparing 3 and 10 days carries lower certainty. Serious adverse events were rare: no deaths, 4 cases of acute rheumatic fever, and 4 cases of post-streptococcal glomerulonephritis among 776, 8,818, and 9,096 participants, respectively, making clinically important differences across treatment durations unlikely. Limitations: Evidence on 3-day courses came almost exclusively from trials of azithromycin, limiting inference about shorter penicillin regimens. Findings apply most directly to high-income settings. Conclusion: These findings challenge the long-standing 10-day standard for pediatric GAS pharyngitis and show that 5 days of oral antibiotics are likely as effective and safe as 10 days. ### Competing Interest Statement The authors have declared no competing interest. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study is a systematic review and dose-response meta-analysis of previously published randomized controlled trials involving human participants. All data were obtained from publicly available published articles identified through systematic searches of bibliographic databases and were available prior to initiation of this study. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors. Canadian Institutes of Health Research, https://ror.org/01gavpb45, 540708

Objectives Despite high diarrheal burden and antibiotic use, C. difficile infection in West Africa is insufficiently studied. This review synthesizes the limited and methodologically diverse evidence on C. difficile in West Africa, summarizing study-level findings on detection, settings, risk factors and strain characteristics to clarify current knowledge gaps and priorities for future research. Methods A systematic literature search was conducted through September 9, 2024, across major global and African databases. The methodological quality, strengths, limitations, and potential sources of bias of included studies were critically evaluated. Due to heterogeneity, findings were synthesized narratively rather than through meta-analysis. Results Across the nine publications from eight studies identified from Nigeria, Ghana, Côte d'Ivoire, and Mali, investigators reported a wide range of findings related to C. difficile detection in both symptomatic and asymptomatic participants. Individual studies also described various participant or clinical characteristics examined within their samples, including demographics, co-infections, antibiotic use, nutritional indicators, and living conditions. Genotyping data, available from only a few studies, showed considerable ribotype diversity, with RT078 detected in a Malian isolate and RT084 most frequently reported in Ghana and Mali. Conclusions The true burden of C. difficile in West Africa remains unknown. Existing evidence comes from a small number of heterogeneous studies conducted in only four countries, providing an insufficient foundation for regional epidemiologic understanding. Collectively, these data underscore major gaps in surveillance and diagnostic capacity; addressing them will require strengthened laboratory infrastructure, increased clinical awareness, and well-designed epidemiological studies to clarify the organism's role and inform appropriate management. Summary This systematic review highlights the rising concern of Clostridioides difficile in West Africa, urging improved diagnostics, clinical awareness, and research to understand its burden and guide effective treatment.

BACKGROUND:Canada has experienced rising rates of bacterial sexually transmitted infections (STIs)-notably syphilis, chlamydia, and gonorrhoea-over the past two decades, especially among gay, bisexual, and other men who have sex with men. Doxycycline pre- and post-exposure prophylaxis (Doxy-PrEP/PEP) has emerged as a potential prevention strategy. However, concerns about antimicrobial resistance (AMR) have prompted further investigation. METHODS:We conducted a systematic review of English-language studies (2013-2023) using PubMed, Embase, Cochrane, and MedRxiv. We included randomized controlled trials (RCTs), cohort, case-control, ecological studies, and systematic reviews that reported on prolonged or recurrent doxycycline use for any indication across all populations. Data were summarized descriptively due to heterogeneity, and risk of bias and GRADE assessments were conducted to rate level of evidence. RESULTS:Sixteen studies across 17 publications met inclusion criteria. Included studies comprised two systematic reviews, eight RCTs, three cohort studies, two cross-sectional studies, and one modeling study. Seven studies assessed tetracycline/doxycycline resistance in STI pathogens and 12 focused on non-STI organisms. Findings were mixed with some studies reporting increased resistance, others minimal or no change. N. gonorrhoeae showed high baseline doxycycline resistance. Evidence on resistance in skin and gut flora was limited and inconsistent, and no clear pattern of co-resistance to other antimicrobials was found. Overall, the quality of evidence was low to very low. CONCLUSION:Evidence on AMR risks from Doxy-PrEP/PEP published up to 2023 was limited and uncertain. Findings are inconsistent and underpowered and emerging evidence could change these conclusions.

Background:Antibiotics are frequently prescribed for aspiration pneumonia in ICU patients. We sought to determine the proportion of ICU patients treated for aspiration pneumonia who meet the diagnostic criteria. Methods:A retrospective review of electronic medical records was conducted in adult patients who were admitted to one of two intensive care units at an Ontario tertiary care hospital between June 1, 2022, and October 1, 2023. Patients who were exposed to antibiotics were first identified and then systematically assessed using electronic medical records to identify occurrences in which aspiration was suspected and antibiotics were potentially used to treat aspiration pneumonia within 14 days of the aspiration event. For each episode, we assessed whether patients met the criteria for either confirmed or suspected aspiration pneumonia. Factors associated with inappropriate prescribing were determined. Results:Of 497 patients treated with antibiotics, 104 (22.0%) were treated for aspiration pneumonia. More than one-half (67 patients, 64.4%) were categorized as either confirmed or suspected aspiration pneumonia. There were 35.6% cases (37 of 104) in which antibiotic courses were prescribed for aspiration pneumonia without meeting the criteria for confirmed or suspected cases. Factors associated with not meeting criteria included prescribing by attending physicians compared with residents or fellows (OR 1.53 [95% CI 0.63 to 3.67], p = 0.34) and admitting patients from the emergency department compared with other non-ICU areas (OR 1.96 [95% CI 0.86 to 4.65], p = 0.12). Intubation was associated with a higher odds of confirmed or suspected aspiration pneumonia (OR 1.11 [95% CI 0.47 to 2.57], p = 0.81). Conclusions:Inappropriate antibiotic prescribing for aspiration pneumonia remains common in the ICU.

QuestionWhich antibiotic prophylaxis regimens are associated with the lowest risk of surgical site infections (SSIs) among patients undergoing elective colorectal surgery?FindingsIn this systematic review and network meta-analysis of 105 randomized clinical trials with 18 273 patients, broad-spectrum penicillins and cephalosporin-based regimens had the strongest associations with reduced risk of SSIs. Regimens including broad-spectrum penicillins were also associated with decreased risk of mortality, but there were no significant differences among regimens with regard to hospital length of stay or adverse events.MeaningIn this study, broad-spectrum penicillins and cephalosporin-based regimens were most strongly associated with SSI prevention, highlighting antibiotic class selection as a key factor in colorectal surgery prophylaxis. This systematic review and network meta-analysis uses data from randomized clinical trials to compare the association of different antibiotic classes and class combinations with clinical and safety outcomes, including surgical-site infection, mortality, adverse events, and length of stay among patients undergoing elective colorectal surgery. ImportanceThe optimal choice of antibiotic prophylaxis in elective colorectal surgery remains uncertain, with most reviews emphasizing timing and route of administration rather than direct comparisons of antibiotic classes.ObjectiveTo compare the outcomes associated with different antibiotic classes and class combinations administered within 24 hours before elective colorectal surgery.Data SourcesMEDLINE, Embase, Cochrane Central, and Scopus were searched from inception to July 17, 2025.Study SelectionEligible studies were randomized clinical trials that enrolled adult patients undergoing elective colorectal procedures and were required to report on surgical site infection (SSI) within 30 days of surgery.Data Extraction and SynthesisData on SSIs, adverse events, all-cause mortality, and length of hospital stay were extracted when available by 2 independent reviewers. A frequentist random-effects model was used for network meta-analysis. Reporting followed the Preferred Reporting Items for Systematic Review and Meta-Analyses, Extension Statement for Reporting of Systematic Reviews Incorporating Network Meta-Analyses of Health Care Interventions.Main Outcomes and MeasuresThe primary outcome was risk of SSI; secondary outcomes were 30-day mortality, adverse events, and length of hospital stay. Risk ratios (RRs) with 95% CIs were calculated for binary outcomes, and mean differences (MDs) with SDs were calculated for continuous outcomes. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.FindingsA total of 105 randomized clinical trials involving 18 273 patients were included. The network included 32 distinct antibiotic nodes defined by antimicrobial class or combination. High to moderate certainty of evidence indicated that, compared with placebo or no antibiotic, several regimens were associated with reduced the risk of SSI. Regimens including broad-spectrum penicillin (RR, 0.26; 95% CI, 0.16-0.42), third-generation cephalosporins (RR, 0.27; 95% CI, 0.16-0.45), a combination of metronidazole and second-generation cephalosporins (RR, 0.27; 95% CI, 0.17-0.44), and tetracyclines (RR, 0.32; 95% CI, 0.20-0.53) were all associated with significant reductions. The antibiotics associated with a significant decrease in mortality compared with placebo were broad-spectrum penicillin (RR, 0.21; 95% CI, 0.05-0.90) and a combination of fluoroquinolones and penicillins (RR, 0.14; 95% CI, 0.03-0.79). No significant differences were observed between antibiotic classes regarding hospital length of stay or adverse events. The certainty of evidence ranged from very low to moderate across outcomes.Conclusions and RelevanceIn this systematic review and network meta-analysis, several antibiotic regimens were associated with substantially reduced risk of SSIs after elective colorectal surgery compared with placebo. Broad-spectrum penicillins had the most consistent benefits, with moderate-certainty evidence supporting reductions in risk of both SSI and mortality.

BACKGROUND:The benefits and harms of using macrolides for asthma remain unclear. OBJECTIVE:As part of upcoming Academy of Allergy, Asthma and Immunology/American College of Allergy, Asthma and Immunology Joint Task Force on Practice Parameters guidelines addressing severe asthma, we systematically reviewed the efficacy and safety of macrolides for asthma. METHODS:We systematically searched MEDLINE, Embase, and CENTRAL to April 12, 2025, for randomized trials comparing macrolides with placebo or standard care for asthma. Paired reviewers independently screened records and extracted data. Individual patient-level data in random effects analysis of covariance models addressed asthma control and asthma-related quality of life. Random effects meta-analyses addressed severe exacerbations and harms. We used the Grading of Recommendations Assessment, Development and Evaluation approach to evaluate certainty of evidence. Our study protocol is registered in PROSPERO (CRD42023408677). RESULTS:Our meta-analysis comprised 19 trials enrolling 1825 participants. Compared with placebo, macrolides improve asthma control (6-item Asthma Control Questionnaire; score range 0-6, lower better; between-group mean difference: -0.23 [95% CI -0.32 to -0.13]; 40.6% vs 21.6% improving by minimally important difference of 0.5 point; high certainty), likely reduce severe exacerbations (incidence rate ratio: 0.75 [95% CI 0.57 to 0.98]; rate difference: 0.26 fewer events per patient-year [95% CI 0.45 to 0.02 fewer events]; moderate certainty), and likely modestly improve quality of life (Asthma Quality of Life Questionnaire; score range 1-7, higher better; mean difference: 0.11 [95% CI -0.06 to 0.29]; 47.6% vs 42.4% improving by minimally important difference of 0.5 points; moderate certainty) with little to no effect on serious adverse events and mortality (high certainty). Relative effects were similar among patients with type 2 high inflammation versus type 2 low inflammation asthma. CONCLUSIONS:Macrolides likely reduce severe exacerbations and improve asthma control and quality of life with little to no difference in serious harms among patients with type 2 high inflammation or type 2 low inflammation asthma.

Background Although most rhinovirus infections are mild and subside quickly, vulnerable populations may experience severe illness. Identifying populations at risk for severe or complicated rhinovirus illness can strengthen the ongoing search for preventative and therapeutic treatments. This systematic review and meta-analysis aimed to summarize the populations at risk for the development of severe or complicated rhinovirus illness. Methods We searched CENTRAL, EMBASE, and MEDLINE in April 2024 for studies reporting risk factors for severe rhinovirus infection, defined as lower respiratory tract infection (LRTI), hospitalization, critical care unit (CCU) admission, mechanical ventilation, or death. We pooled odds ratios using random-effects meta-analysis, assessed risk of bias using the Newcastle-Ottawa Scale, and rated the certainty of evidence using the GRADE framework. Results From 29 observational studies (n = 13,185 participants), we analyzed 13 risk factor-outcome combinations. With high certainty, age < 1 year and premature birth are not associated with the risk of LRTI, and diabetes mellitus is not associated with mortality. With moderate certainty, any comorbidity and pulmonary comorbidity are probably associated with increased risk of LRTI, age > 18 years and malignancy are probably associated with increased risk of mortality, and malignancy is probably associated with an increased risk of CCU admission. Many risk factors lacked sufficient evidence for meta-analysis. Conclusions Individuals with comorbidities are at greater risk of severe rhinovirus illness. Our findings can inform clinical risk stratification and guide the development and targeted use of emerging therapies. Further comprehensive research is required to elucidate additional risk factors and strengthen the evidence

BACKGROUND:Respiratory syncytial virus (RSV) can cause serious disease in older adults (OAs), particularly those with comorbidities. It is a leading cause of acute respiratory illness and lower respiratory tract infections in adults ≥60 years. Its impact on morbidity, mortality, and healthcare systems is becoming evident. Questions about the burden of disease (BoD) are raised due to underdiagnosis and the similarity with other respiratory illnesses. First opportunities for prevention came in 2023 and 2024, with vaccines approved for ≥60 years, expanding eligibility to additional age groups. RESEARCH DESIGN AND METHODS:A modified Delphi approach through a questionnaire survey and virtual consensus workshop with 27 experts in respiratory and infectious diseases from 12 emerging market countries was done to reach consensus on diagnosis, prevention, and treatment of RSV in OAs. RESULTS:The panel recommends the introduction of a universal vaccination program for all adults aged ≥70 years, and vaccination for all adults aged ≥60 years with comorbidities. The need for increased awareness, better testing, and national and international guidelines was also agreed. CONCLUSION:The agreements highlight that RSV vaccination for OAs should be prioritized. Educating clinicians and patients, improving surveillance, and integrating RSV vaccination into health policies are key to reducing BoD in OAs.

Background:Malaria is typically diagnosed using rapid antigen tests and microscopy. This case describes an unusual presentation of Plasmodium falciparum, initially detected via 16S rDNA testing of pericardial fluid identifying apicoplast DNA-a finding not previously reported in the literature. Case Summary:A septuagenarian Nigerian man visiting Canada presented with shortness of breath, tachycardia, tachypnea, anemia, and a pericardial effusion. Pericardiocentesis yielded serosanguineous fluid, and imaging revealed multifocal opacities. Blood and fluid cultures were negative for bacterial organisms. After briefly leaving the hospital against medical advice, he returned in respiratory distress and required intubation for acute respiratory distress syndrome. He received empiric antibiotics for rickettsial infection (due to positive serology) and presumed sepsis. Further workup, including pericardial fluid 16S rDNA PCR and sequencing, identified P. falciparum apicoplast DNA. This was confirmed by malaria antigen and Plasmodium-specific PCR testing of the fluid alongside PCR of whole blood, though microscopy and antigen tests remained negative. Hemozoin-like structures were also identifiable in the pericardial fluid. He was treated with a 3-day course of atovaquone-proguanil for malaria, with subsequent clinical improvement. He remains well on follow-up. Conclusion:This case underscores an uncommon presentation of P. falciparum and, though not a standard or recommended diagnostic tool for malaria, in this case, 16S rDNA analysis aided in the diagnosis. Clinicians should maintain malaria in the differential for patients from endemic regions. Multidisciplinary collaboration was essential in achieving the diagnosis.

BACKGROUND:Seasonal influenza vaccination may be effective against severe influenza disease. OBJECTIVES:To assess evidence on the real-world effectiveness of influenza vaccination in preventing severe influenza-related outcomes. METHODS:Data sources: PubMed, Ovid, and Cochrane CENTRAL from inception to September 24, 2024. STUDY ELIGIBILITY CRITERIA:Observational test-negative design studies reporting influenza vaccine effectiveness (IVE) against influenza-associated hospitalisation, death, pneumonia, intensive care unit admission, or ventilatory support. PARTICIPANTS:Hospitalized adults and children with laboratory-confirmed influenza and inpatient controls who tested negative for influenza infection. INTERVENTIONS:Influenza vaccination. ASSESSMENT OF RISK OF BIAS:Newcastle-Ottawa Scale and Grading of Recommendations Assessment, Development, and Evaluation were used to assess study quality and evidence certainty. METHODS OF DATA SYNTHESIS:We extracted study characteristics and ORs or IVE estimates and corresponding 95% CI. Both crude and adjusted estimates were considered and analysed using a random-effects model. We calculated the pooled IVE overall and by season, age group, circulating strains, vaccine type, and match between the vaccine and circulating strains. RESULTS:Overall, 7727 publications were identified, 461 reviewed, and 165 included. Pooled IVE was 42% (95% CI: 39-44) against influenza-associated hospitalisation (very low certainty), 36% (95% CI: 24-46) against death (no certainty), 51% (95% CI: 36-63) against pneumonia (low certainty), 52% (95% CI: 38-63) against intensive care unit admission (very low certainty), and 55% (95% CI: 44-64) against ventilatory support (low certainty). IVE varied by age and was generally higher (up to 2-fold) in children compared to adults. Higher IVE was observed against influenza A(H1N1) compared to A(H3N2) and in seasons with good vaccine match. Hospitalisation IVE was slightly higher for quadrivalent (45% (95% CI: 32-56)) compared to trivalent (36% (95% CI: 27-43)) vaccine. CONCLUSIONS:Seasonal influenza vaccination moderately reduces severe influenza-related outcomes, particularly in children, against A(H1N1), and with a good vaccine-strain match. PROSPERO REGISTRATION:CRD42023476003.

Background Coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continues to have a significant impact worldwide, in part due to a reduction in neutralising antibody protection provided by vaccines targeting monovalent spike antigens related to immune escape. Development of vaccines amenable for respiratory mucosal delivery that provide broad and durable immunity are needed. This study aims to determine the safety and immunogenicity of a single inhaled dose of a replication-deficient chimpanzee adenovirus type 68 vector expressing a trivalent transgene cassette of SARS-CoV-2 S1 domain of spike, nucleocapsid and RNA polymerase genes (ChAd-triCoV/Mac). Methods We plan to recruit 350 nonpregnant adults aged 18-65 who have previously received three intramuscular SARS-CoV-2 mRNA vaccines in this 24-week, multicentre, double-blind, parallel-group, phase II, two-sided superiority randomised controlled trial. Participants will be randomised 2:1 to receive either a single inhaled dose of ChAd-triCoV/Mac or placebo, both aerosolised via the AeroNeb (R) Solo vibrating mesh nebuliser. A subset of separately randomised participants will undergo bronchoalveolar lavage (BAL). The co-primary outcome to be analysed in the per-protocol population is SARS-CoV-2 antigen-specific CD4+ and CD8+ T-cell responses measured at 2 weeks in the peripheral blood; solicited adverse event frequency to day 7 and unsolicited to day 28. In the BAL sub-study, the co-primary outcome will also include BAL fluid SARS-CoV-2 antigen-specific CD4+ and CD8+ T-cell responses measured at 4 weeks. Conclusion This placebo-controlled phase 2 randomised trial will test the safety and immunogenicity of an inhaled, nebulised ChAd-triCoV/Mac SARS-CoV-2 vaccine that is novel in its administration route and targeting of multiple viral epitopes. The results will provide further information regarding the mucosal T-cell response to immunisation.

Background:Common cold coronaviruses were a frequent cause of respiratory infections in older adults living in congregate care homes before the coronavirus disease 2019 pandemic, which may influence immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and infection. We investigated humoral and cellular immune responses to prior common cold coronaviruses and SARS-CoV-2, how they are affected by SARS-CoV-2 vaccination and infection, and their associations with Omicron BA.1 SARS-CoV-2 infections in residents of long-term care and retirement homes. Methods:In SARS-CoV-2 infection-naive residents with 3 monovalent messenger RNA SARS-CoV-2 vaccinations, we measured serum anti-receptor binding domain (RBD) immunoglobulin (Ig) G and IgA antibody titers against SARS-CoV-2 and common cold human coronavirus (HCoV) NL63, HCoV-OC43, and HCoV-229E; ancestral and Omicron BA.1 neutralizing antibodies; and CD4+ and CD8+ T-cell activation responses to membrane, nucleocapsid, and spike proteins. We examined the relationships of common cold coronavirus and SARS-CoV-2 humoral immune responses, whether antibody and T-cell responses changed after SARS-CoV-2 messenger RNA vaccination or infection, and their associations with Omicron BA.1 infection. Results:Anti-RBD IgG HCoV-OC43 titers were positively correlated with SARS-CoV-2 anti-RBD IgG and neutralizing antibody titers. Common cold coronavirus anti-RBD IgA titers, but not anti-RBD IgG titers, increased after SARS-CoV-2 vaccination or infection, and many residents had cross-reactive T cells. Common cold coronavirus humoral immunity was similar in residents without and those with subsequent Omicron BA.1 infection. Conclusions:Despite frequent exposure, and associations of common cold coronavirus and vaccine-induced SARS-CoV-2 humoral immunity, preexisting common cold coronavirus immunity was not associated with Omicron BA.1 infection in residents of long-term care and retirement communities.

BACKGROUND:Sex-differences in influenza vaccine efficacy and immunogenicity remain inconclusive, with limited evidence in pediatric populations. Hutterite communities provide a unique environment for evaluating vaccine responses due to their controlled social and environmental conditions. Understanding sex-differences could help inform targeted vaccination strategies. METHODS:This study analyzed data from three cluster-randomized trials (2008-2017) involving Canadian Hutterite children aged 6 months to 15 years. Participants received season-specific influenza vaccines across different seasons (Trial 1: trivalent influenza vaccine (TIV) versus hepatitis A vaccine); Trial 2: live attenuated influenza vaccine versus TIV; Trial 3: adjuvanted trivalent influenza vaccine versus quadrivalent influenza vaccine). Influenza incidence was assessed within trial groups by sex and vaccine efficacy was assessed using Cox proportional hazards models, adjusting for sex, age, and intervention group, with clustering by colony, and effect modification of vaccine by sex. Immunogenicity was measured using hemagglutination inhibition (HAI) antibody responses expressed as geometric mean titers (GMT), geometric mean fold rise (GMFR), and seroconversion rates (SCR). RESULTS:Across all trials, there were no consistent sex differences in either vaccine efficacy or immunogenicity. In Trial 1 however, there was effect modification of sex by vaccine in a trial with non-influenza vaccine control group. Immunogenicity results also revealed few statistically significant sex-differences in GMT, GMFR, or SCR. CONCLUSIONS:These findings suggest that sex may not be a major factor in vaccine response in pediatric populations, but may be more likely to be detected in influenza vaccine trials with a non-influenza vaccine control group.

INTRODUCTION:Dengue is a mosquito-borne disease prevalent in Latin America and the Caribbean. Transmission is determined by ecological, biological and social (eco-bio-social) factors. Understanding the knowledge, attitudes, practices and perceptions of dengue's eco-bio-social factors among at-risk populations is essential for dengue prevention. We used the Ecohealth approach to investigate the socioeconomic and demographic factors associated with dengue knowledge, attitudes, practices and perceptions among residents of São Paulo. METHODS:We conducted a concurrent nested mixed-methods study between May and November 2024 using an online knowledge, attitudes, practices and perceptions survey, focus group discussions and Photovoice activity. Quantitative data were analysed using descriptive statistics and multivariable logistic regressions. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were calculated. Qualitative data were analysed thematically. Integration from both method strands used a weaving, narrative approach. FINDINGS:Overall, 388 participants completed the knowledge, attitudes, practices and perceptions survey. Having some or a lot of vegetation around the home (aOR 2.63, 95% CI: 1.05-6.60; aOR 3.90, 95% CI: 1.57-9.69, respectively) and never having dengue (self-reported; aOR 1.80, 95% CI: 1.10-2.94) were associated with high knowledge scores. Higher education was associated with positive vaccine attitudes (aOR 2.04, 95% CI: 1.14-3.64). Women (aOR 1.57, 95% CI: 1.01-2.45) and individuals with three and more than three household members (aOR 2.04, 95% CI: 1.07-3.87; aOR 3.10, 95% CI: 1.62-5.94, respectively) had higher odds of using mosquito repellents at home. Those who earned more than R$6000 monthly had higher odds of having a high perception of self-efficacy to prevent dengue compared to those who earned less than R$2000 monthly (aOR 2.03, 95% CI: 1.08-3.82). Focus group discussions and Photovoice participants perceived climate change as a risk factor of dengue transmission. The high cost of mosquito repellents was a perceived challenge to prevention. CONCLUSION:Several individual- and household-level factors were associated with dengue knowledge, attitudes, practices and perceptions in São Paulo. There is a need to increase public awareness about dengue and its vaccine. Future research should assess the effectiveness of community-tailored interventions to reduce dengue risk in this urban, climate-vulnerable setting.