{"title":"Pooled analysis of the MANTICO2 and MONET randomized controlled trials comparing drug efficacy for early treatment of COVID-19 during Omicron waves","authors":"","doi":"10.1016/j.jinf.2024.106294","DOIUrl":"10.1016/j.jinf.2024.106294","url":null,"abstract":"<div><h3>Background</h3><div>The clinical effectiveness of early therapies for mild-to-moderate COVID-19, comparing antivirals and monoclonal antibodies (mAbs) during the Omicron era, has not been conclusively assessed through a post-approval comparative trial. We present a pooled analysis of two randomized clinical trials conducted during Omicron waves.</div></div><div><h3>Methods</h3><div>The MANTICO2/MONET trial is a pooled analysis of two multicentric, independent, phase-4, three-arm, superiority, randomized, open-label trials. Nonhospitalized patients with early mild-to-moderate COVID-19 (≤5 days after symptoms’ onset) and at least one risk factor for disease progression were randomized 1:1:1 to receive 500 mg of intravenous sotrovimab (SOT) or 600 mg of intramuscular tixagevimab/cilgavimab (TGM/CGM) or oral 5-days course of nirmatrelvir/ritonavir (NMV/r) 300/100 mg BID. Primary outcome was COVID-19-related hospitalization or death within 29 days after randomization. Fisher’s exact test for pooled data and incidence of failure was reported as overall and by arm with respective 95% CI. Pairwise comparisons across the arms were conducted using unadjusted exact logistic regression. An analysis by means of a doubly robust marginal model using augmented inverse probability weighting (AIPW) was also conducted to estimate the potential outcomes (Pom) in each treatment group and their difference by the average treatment effect (ATE). Analysis of symptom persistence within 30 days after randomization was performed using a 2-level hierarchical mixed-effects logistic model with a random intercept at the patient’s level. Point estimates and 95% confidence intervals were adjusted for age and sex and calculated using ANOVA-like methods for the mixed effects logistic model. These trials are registered with the European Clinical Trials Database, EudraCT2021-002612-31 (MANTICO2) and EudraCT2021–004188-28 (MONET) and ClinicalTrials.gov, NCT05321394 (MANTICO2).</div></div><div><h3>Findings</h3><div>Between March 2022 and February 2023, 991 patients (SOT = 332, TGM/CGM = 327, NMV/r = 332) were enrolled in 15 Italian centers. The overall mean age was 66 years; 482 participants (48.80%) were male, and 856 were vaccinated with at least a primary course (86%). Among the 8/991 hospitalizations observed, one resulted in death. The overall estimate of failure was 0.81% (95%CI; 0.35–1.58%). The odds ratio (OR) for the primary outcome in the NMV/r arm compared to the TGM/CGM and SOT arms was 8.41 (95% CI 1.21 to infinity; p = 0.015) and 2.42 (95% CI 0.19 to infinity; p = 0.499), respectively. No significant difference was observed between SOT and TGM/CGM (OR 0.32; 95% CI 0.032–1.83; p = 0.174). Results were similar when we applied the marginal weighted model accounting for potential residual confounding bias. There was no evidence for a difference in the prevalence of symptoms between treatment groups, except for cough, which was higher in the SOT group compared to the ","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":null,"pages":null},"PeriodicalIF":14.3,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142331467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Revealing patterns of SARS-CoV-2 variant emergence and evolution using RBD amplicon sequencing of wastewater","authors":"","doi":"10.1016/j.jinf.2024.106284","DOIUrl":"10.1016/j.jinf.2024.106284","url":null,"abstract":"<div><h3>Objectives</h3><div>Rapid evolution of SARS-CoV-2 has resulted in the emergence of numerous variants, posing significant challenges to public health surveillance. Clinical genome sequencing, while valuable, has limitations in capturing the full epidemiological dynamics of circulating variants in the general population. This study aimed to monitor the SARS-CoV-2 variant community dynamics and evolution using receptor-binding domain (RBD) amplicon sequencing of wastewater samples.</div></div><div><h3>Methods</h3><div>We sequenced wastewater from El Paso, Texas, over 17 months, compared the sequencing data with clinical genome data, and performed biodiversity analysis to reveal SARS-CoV-2 variant dynamics and evolution.</div></div><div><h3>Results</h3><div>We identified 91 variants and observed waves of dominant variants transitioning from BA.2 to BA.2.12.1, BA.4&5, BQ.1, and XBB.1.5. Comparison with clinical genome sequencing data revealed earlier detection of variants and identification of unreported outbreaks. Our results also showed strong consistency with clinical data for dominant variants at the local, state, and national levels. Alpha diversity analyses revealed significant seasonal variations, with the highest diversity observed in winter. By segmenting the outbreak into lag, growth, stationary, and decline phases, we found higher variant diversity during the lag phase, likely due to lower inter-variant competition preceding outbreak growth.</div></div><div><h3>Conclusions</h3><div>Our findings underscore the importance of low transmission periods in facilitating rapid mutation and variant evolution. Our approach, integrating RBD amplicon sequencing with wastewater surveillance, demonstrates effectiveness in tracking viral evolution and understanding variant emergence, thus enhancing public health preparedness.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":null,"pages":null},"PeriodicalIF":14.3,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142331469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Clinical and epidemiological investigation of human infection with zoonotic parasite Trypanosoma dionisii in China","authors":"","doi":"10.1016/j.jinf.2024.106290","DOIUrl":"10.1016/j.jinf.2024.106290","url":null,"abstract":"<div><h3>Background</h3><div>Trypanosomiasis continues to pose a global threat to human health, with human infection mainly caused by <em>Trypanosoma brucei</em> and <em>Trypanosoma cruzi.</em></div></div><div><h3>Methods</h3><div>We present a 30-year-old pregnant woman with persistent high fever from Shandong Province, China. High-throughput sequencing revealed the presence of <em>Trypanosoma dionisii</em> in blood. We conducted an analysis of the patient’s clinical, epidemiological, and virological data.</div></div><div><h3>Results</h3><div>The patients exhibited fever, shortness of breath, chest tightness, accompanied by change in liver function and inflammatory response. She made a full recovery without any long-term effects. <em>T. dionisii</em> was detected in blood collected 23 days after onset of illness. The 18S rRNA gene sequence showed close similarity to <em>T. dionisii</em> found in bats from Japan, while the <em>gGAPDH</em> gene was closely related to <em>T. dionisii</em> from bats in Mengyin County, Shandong Province. Phylogenetic analysis demonstrated the current <em>T. dionisii</em> belongs to clade B within its species group. Positive anti-<em>Trypanosoma</em> IgG antibody was detected from the patient on Day 23, 66 and 122 after disease onset, as well as the cord blood and serum from the newborn. Retrospective screening of wild small mammals captured from Shandong Province revealed a prevalence rate of 0.54% (7/1304) for <em>T. dionisii</em>; specifically among 0.81% (5/620) of <em>Apodemus agrarius</em>, and 0.46% (2/438) of <em>Mus musculus</em>.</div></div><div><h3>Conclusions</h3><div>The confirmation of human infection with <em>T. dionisii</em> underscores its potential as a zoonotic pathogen, while the widespread presence of this parasite in rodent and bat species emphasizes the emerging threat it poses to human health.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":null,"pages":null},"PeriodicalIF":14.3,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142331428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Severity of respiratory syncytial virus compared with SARS-CoV-2 and influenza among hospitalised adults ≥65 years","authors":"","doi":"10.1016/j.jinf.2024.106292","DOIUrl":"10.1016/j.jinf.2024.106292","url":null,"abstract":"<div><h3>Introduction</h3><div>Our aim was to estimate the risk of pneumonia, admission to intensive care unit (ICU) or death in individuals ≥65 years old admitted to hospital with RSV, compared to influenza or COVID-19.</div></div><div><h3>Methods</h3><div>We included hospitalised patients from Severe Acute Respiratory Infection Surveillance in Spain between 2021–2024, aged ≥65 years, laboratory confirmed for RSV, influenza or SARS-CoV-2. Using a binomial regression with logarithmic link, we estimated the relative risk (RR) of pneumonia, ICU admission and in-hospital mortality, in patients with RSV compared to influenza or SARS-CoV-2, adjusting for age, sex, season and comorbidities. We stratified the estimates by vaccination status for influenza or SARS-CoV2.</div></div><div><h3>Results</h3><div>Among patients unvaccinated for influenza or SARS-CoV-2, those with RSV had similar or lower risk of pneumonia [vs. influenza: RR= 0.91 (95% Confidence Interval: 0.72–1.16); vs. SARS-CoV-2: 0.81 (0.67–0.98)], ICU admission [vs. influenza: 0.93 (0.41–2.08); vs. SARS-CoV-2: 1.10 (0.61–1.99)] and mortality [vs. influenza: 0.64 (0.32–1.28); vs. SARS-CoV-2: 0.56 (0.30–1.04)]. Among the vaccinated, results were largely similar except for a higher risk of ICU admission with RSV [vs. influenza: 2.13(1.16–3.89); vs. SARS-CoV-2: 1.83 (1.02–3.28)]</div></div><div><h3>Conclusions</h3><div>RSV presented similar or lower intrinsic severity than influenza or SARS-CoV2. Among vaccinated patients, RSV was associated to higher ICU-admission, suggesting the potential for preventive RSV vaccination.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":null,"pages":null},"PeriodicalIF":14.3,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142331470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"N-protein vaccine is effective against COVID-19: Phase 3, randomized, double-blind, placebo-controlled clinical trial","authors":"","doi":"10.1016/j.jinf.2024.106288","DOIUrl":"10.1016/j.jinf.2024.106288","url":null,"abstract":"<div><h3>Background</h3><div>Despite the success of first-generation COVID-19 vaccines targeting the spike (S) protein, emerging SARS-CoV-2 variants have led to immune escape, reducing the efficacy of these vaccines. Additionally, some individuals are unable to mount an effective immune response to S protein-based vaccines. This has created a need for alternative vaccine strategies that are less susceptible to mutations and capable of providing broad and durable protection. This study aimed to evaluate the efficacy and safety of a novel COVID-19 vaccine based on the full-length recombinant nucleocapsid (N) protein of SARS-CoV-2.</div></div><div><h3>Methods</h3><div>We conducted a prospective, multicenter, randomized, double-blind, placebo-controlled phase 3 clinical trial (NCT05726084) in Russia. Participants (n = 5229) were adults aged 18 years and older, with a BMI of 18.5–30 kg/m², and without significant clinical abnormalities. They were randomized in a 2:1 ratio to receive a single intramuscular dose of either the N protein-based vaccine (50 µg) or placebo. Randomization was done through block randomization, and masking was ensured by providing visually identical formulations of vaccine and placebo. The primary outcome was the incidence of symptomatic COVID-19 confirmed by PCR more than 15 days after vaccination within a 180-day observation period, analyzed on an intention-to-treat basis.</div></div><div><h3>Findings</h3><div>Between May 18, 2023, and August 9, 2023, 5229 participants were randomized, with 3486 receiving the vaccine and 1743 receiving the placebo. Eight cases of PCR-confirmed symptomatic COVID-19 occurred in the vaccine group (0.23%) compared to 27 cases in the placebo group (1.55%), yielding a vaccine efficacy of 85.2% (95% CI: 67.4–93.3; p < 0.0001). Adverse events were mostly mild and included local injection site reactions. There were no vaccine-related serious adverse events.</div></div><div><h3>Interpretation</h3><div>The N protein-based COVID-19 vaccine demonstrated significant efficacy and a favorable safety profile, suggesting it could be a valuable addition to the global vaccination effort, particularly in addressing immune escape variants and offering an alternative for those unable to respond to S protein-based vaccines. These results support the continued development and potential deployment of N protein-based vaccines in the ongoing fight against COVID-19.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":null,"pages":null},"PeriodicalIF":14.3,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142331466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Platform Trial In COVID-19 Priming and BOOsting (PICOBOO): The immunogenicity, reactogenicity, and safety of different COVID-19 vaccinations administered as a second booster (fourth dose) in AZD1222 primed individuals aged 50-<70 years old","authors":"","doi":"10.1016/j.jinf.2024.106286","DOIUrl":"10.1016/j.jinf.2024.106286","url":null,"abstract":"<div><h3>Objectives</h3><div>PICOBOO is a randomised, adaptive trial evaluating the immunogenicity, reactogenicity, and safety of COVID-19 booster strategies. We report data for second boosters among individuals 50-<70 years old primed with AZD1222 (50-<70y-AZD1222) until Day 84.</div></div><div><h3>Methods</h3><div>Immunocompetent adults who received any first booster ≥three months prior were eligible. Participants were randomly allocated to BNT162b2, mRNA-1273 or NVX-CoV2373 1:1:1. The concentrations of ancestral anti-spike immunoglobulin were summarised as the geometric mean concentrations (GMC). Reactogenicity and safety outcomes were captured. Additional analyses including neutralising antibodies were performed on a subset. ACTRN12622000238774.</div></div><div><h3>Results</h3><div>Between Mar 2022 and Aug 2023, 743 participants were recruited and had D28 samples; 155 belonged to the 50-<70y-AZD1222 stratum. The mean adjusted GMCs (95% credible intervals) were 20,690 (17 555−23 883), 23,867 (20 144−27 604) and 8654 (7267−9962) U/mL at D28 following boosting with BNT162b2, mRNA-1273 and NVX-CoV2372, respectively, and 10,976 (8826−13 196), 15,779 (12 512−19 070) and 6559 (5220−7937) U/mL by D84. IgG against Omicron BA.5 was 2.7–2.9 times lower than the ancestral strain. Limited neutralisation against Omicron subvariants was found following all vaccines. Severe reactogenicity events were <4%.</div></div><div><h3>Conclusions</h3><div>All vaccines were immunogenic with more rapid waning after mRNA vaccines. These data support boosting with vaccines with greater specificity for circulating Omicron subvariants.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":null,"pages":null},"PeriodicalIF":14.3,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142331471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Trends in hospitalisations for lower respiratory infections after the COVID-19 pandemic in France","authors":"","doi":"10.1016/j.jinf.2024.106287","DOIUrl":"10.1016/j.jinf.2024.106287","url":null,"abstract":"<div><h3>Objectives</h3><div>We aimed to evaluate the impact of the pandemic and post-pandemic periods on hospital admissions for LRTI, with a focus on patients with chronic respiratory disease (CRD).</div></div><div><h3>Methods</h3><div>From July 2013 to June 2023, monthly numbers of adult hospitalisations for LRTI (excluding SARS-CoV-2) were extracted from the French National Hospital Discharge Database. They were modelled by regressions with autocorrelated errors. Three periods were defined: (1) early pandemic and successive lockdowns; (2) gradual lifting of restrictions and widespread SARS-CoV-2 vaccination; (3) withdrawal of restriction measures.</div></div><div><h3>Results</h3><div>Pre-pandemic incidence was 96 (90.5 to 101.5) per 100,000 population. Compared with the pre-pandemic period, no more seasonality and significant reductions were estimated in the first two periods: −43.64% (−50.11 to −37.17) and −32.97% (−39.88 to −26.05), respectively. A rebound with a positive trend and a seasonal pattern was observed in period 3. Similar results were observed for CRD patients with no significant difference with pre-pandemic levels in the last period (−9.21%; −20.9% to 1.67%), albeit with differential changes according to the type of CRD.</div></div><div><h3>Conclusions</h3><div>COVID-19 pandemic containment measures contributed to changes in LRTI incidence, with a rapid increase and return to a seasonal pattern after their lifting, particularly in patients with CRD.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":null,"pages":null},"PeriodicalIF":14.3,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142331473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Long-term morbidity and mortality of patients who survived past 30 days from bloodstream infection: A population-based retrospective cohort study","authors":"","doi":"10.1016/j.jinf.2024.106283","DOIUrl":"10.1016/j.jinf.2024.106283","url":null,"abstract":"<div><h3>Background</h3><div>For bloodstream infections (BSI), treatment and research have focused on short term mortality. The objective of this study was to describe the 1-year mortality and morbidity in survivors of bloodstream infection when compared to patients with negative blood cultures.</div></div><div><h3>Methods</h3><div>We conducted a population-based retrospective cohort study using Ontario administrative databases. Patients were included if they had a blood culture taken from January 1, 2014, to December 31, 2021, and survived past 30 days from blood culture collection. They were followed for the subsequent year. Outcomes were compared among patients with BSI and those without BSI, including all-cause mortality, stroke, myocardial infarction (MI), congestive heart failure (CHF) exacerbation, new start dialysis and admission to a long-term care (LTC) facility. Prognostic factors were balanced using overlap weighting of propensity scores, and a survival or competing risk model was used to describe time-to-event.</div></div><div><h3>Results</h3><div>Of 981,341 patients undergoing blood culture testing, 99,080 (10.1%) patients had a BSI and 882,261 (89.9%) patients did not. Outcomes were all more common among those with BSI as compared to those without BSI, including all-cause mortality (16,764 [16.9%] vs. 84,480 [9.6%]), stroke (1016 [1.0%] vs. 4680 [0.5%]), MI (1043 [1.1%] vs. 4547 [0.5%]), CHF exacerbation (2643 [2.7%] vs. 13,200 [1.5%]), new start dialysis (1703 [1.7%] vs. 2749 [0.3%]), and LTC admission (4231 [4.3%] vs. 13,016 [1.5%]). BSI had an adjusted hazard ratio of 1.10 (95% CI 1.08–1.12, P < 0.0001) for mortality, subdistribution hazard ratio (sHR) of 1.27 (95% CI 1.19–1.37, P < 0.0001) for stroke, sHR of 1.18 (95% CI 1.10–1.26, P < 0.0001) for MI, sHR of 1.05 (95% CI 1.01–1.10, P = 0.0176) for CHF exacerbation, sHR of 3.42 (95% CI 3.21–3.64, P < 0.0001) for new start dialysis and sHR of 1.87 (95% CI 1.80–1.94, P < 0.0001) for LTC admission.</div></div><div><h3>Conclusion</h3><div>BSI survivors have substantial long-term mortality and morbidity including stroke, MI, new start dialysis and functional decline leading to LTC admission.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":null,"pages":null},"PeriodicalIF":14.3,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142326612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Corrigendum to “Patients with transplantation have reduced mortality in bacteraemia: Analysis of data from a randomised trial” [J Infect 85 (2022) 17–23]","authors":"","doi":"10.1016/j.jinf.2024.106281","DOIUrl":"10.1016/j.jinf.2024.106281","url":null,"abstract":"","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":null,"pages":null},"PeriodicalIF":14.3,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142320328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comparison of short- and long-term humoral immune responses to pneumococcal polysaccharide and glycoconjugate vaccines in an HIV-infected population","authors":"","doi":"10.1016/j.jinf.2024.106282","DOIUrl":"10.1016/j.jinf.2024.106282","url":null,"abstract":"<div><h3>Background</h3><div>Immunisation is recommended internationally to protect against pneumococcal infections in HIV-infected adults. However, vaccination schedule designs are mostly based on studies of initial rather than long-term antibody responses. This UK observational study investigated the short- and long-term antibody responses to polysaccharide and glycoconjugate pneumococcal vaccines in an adult HIV-infected cohort.</div></div><div><h3>Methods</h3><div>We studied a subgroup of 152 of 839 participants from the AIR (Assessment of Immune Responses to Routine Immunisations in HIV-infected Adults, ISRCTN95588307) study that had received pneumococcal vaccinations and had blood samples collected pre- and post-vaccination, as well as at least annually for four subsequent calendar years. Patients received either Pneumovax-23 (PPV, N = 89) or Prevenar-13 (PCV, N = 63) as their primary vaccine, with immunity assessed by measuring IgG antibody concentrations for 12 pneumococcal polysaccharide serotypes (PnPS). The primary outcome was achieving IgG antibody concentrations above the recommended World Health Organisation (WHO) threshold of 0.35 µg/mL for at least 8/12 of the PnPS assessed (WHO<sub>≥8/12PnPS</sub>). Patients who did not achieve WHO<sub>≥8/12PnPS</sub> after the primary vaccination were offered further vaccination with PCV; booster vaccinations with PCV were additionally offered to those where antibody levels subsequently fell below the WHO<sub>≥8/12PnPS</sub> threshold.</div></div><div><h3>Results</h3><div>Patients receiving PCV as their primary pneumococcal vaccine were significantly more likely to achieve WHO<sub>≥8/12PnPS</sub> after a single vaccine dose than those receiving PPV (54% vs. 33%, p = 0.012). This difference persisted following booster vaccination with PCV, with cumulative rates of WHO<sub>≥8/12PnPS</sub> in those receiving PCV vs. PPV as the primary vaccine of 88% vs. 67% and 100% vs. 85% after receiving up to one and two booster vaccinations, respectively. Where WHO<sub>≥8/12PnPS</sub> was achieved, this persisted significantly longer in those receiving PCV as their primary vaccine compared to PPV (median: 23.5 vs. 11.1 months; p = 0.010).</div></div><div><h3>Conclusions</h3><div>Immunisation with PCV resulted in quantitatively greater antibody responses than immunisation with PPV in a cohort of HIV-infected UK adults. Individuals receiving PCV as their primary vaccine required fewer total pneumococcal vaccine doses to achieve WHO<sub>≥8/12PnPS</sub> and experienced greater duration of time above this threshold than those with PPV as the primary vaccine. However, the median longevity of both vaccine responses was relatively short, which supports the use of ongoing booster doses using high-valency glycoconjugate vaccines to sustain WHO<sub>≥8/12PnPS</sub> threshold antibody levels.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":null,"pages":null},"PeriodicalIF":14.3,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142331429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}