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Background: In infants that were exposed to biologics in utero, gastroenterology societal guidelines have either recommended against administration of the live rotavirus vaccine until 6-12 months of age or until serum biologic levels are undetectable. We performed a systematic review to evaluate the safety of rotavirus vaccination in biologic-exposed infants., Methods: EMBASE, PubMed, Scopus, and Cochrane databases were searched from 2006 to 2024 for original data reporting on the safety of rotavirus vaccination in infants that were exposed to anti-tumor necrosis factors (TNFs) (ie, infliximab, adalimumab, golimumab, certolizumab) and non-TNF biologics (ie, vedolizumab, ustekinumab, rizankizumab, mirikizumab) in utero., Results: A database search yielded 7185 screening results of which 10 studies met inclusion criteria. There were over 300 instances of rotavirus vaccination in biologic-exposed infants (n = 162 exposed to anti-TNFs, n = 142 exposed to non-TNF biologics). Biologic-exposed infants were not at an increased risk of severe adverse events or adverse events of any severity related to rotavirus vaccination., Conclusions: Administration of the live rotavirus vaccine appears to be safe in biologic-exposed infants. As such, with careful examination of the risks and benefits, there may be a role for rotavirus vaccination in this population., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

This prospective study enrolled healthcare workers (HCWs) who were nonresponders following at least 5 doses of aluminum-adjuvanted hepatitis B vaccine who received the 2-dose Heplisav-B (HepB-CpG) (Dynavax Technologies Corporation, Emeryville, CA) series. After 2 doses of HepB-CpG, 43/47 (91%) participants, and with 1 dose, 41/49 (84%) responded. HepB-CpG could be the preferred vaccine in HCW nonresponders. Clinical Trials Registration. Clinicaltrials.gov NCT04456504., Competing Interests: Potential conflicts of interest. Dr. Caldera has received research support from Novavax and Takeda Pharmaceuticals. He has been a consultant for Takeda, Arena Pharmaceuticals, GSK, and Celgene. Dr. Hayney received research support from Novavax and Takeda Pharmaceuticals. She has served as a consultant and speaker for GSK vaccines. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: There is evidence that SARS-CoV2 infection can increase the risk of herpes zoster (HZ) in the general population. However, the risk in patients with inflammatory bowel disease (IBD) is not known., Methods: The TriNetX database was utilized to conduct a retrospective cohort study in patients with IBD after SARS-CoV2 infection and patients without a SARS-CoV2 infection (IBD control cohort). The primary outcome was to evaluate the risk of HZ between the 2 cohorts. One-to-one (1:1) propensity score matching was performed for demographic parameters, HZ risk factors and IBD medications between the 2 cohorts. Adjusted odds ratio (aOR) with 95% confidence interval (CI) were calculated., Results: After propensity score matching, patients with IBD with a SARS-CoV2 infection were at an increased risk for HZ (aOR, 2.16; 95% CI, 1.53-3.04) compared with IBD control cohort in the pre-COVID-19 vaccine era. There was no difference in the risk (aOR, 0.87; 95% CI, 0.44-1.75) of a composite outcome of HZ complications (hospitalization, post-herpetic neuralgia, and neurologic complications) between the 2 cohorts. The IBD SARS-CoV2 cohort was also at an increased risk for HZ (aOR, 3.04; 95% CI, 1.48-6.24) compared with IBD control cohort in the postvaccine era. However, the risk of HZ in the postvaccine era was decreased (aOR, 0.45; 95% CI, 0.27-0.76) compared with IBD SARS-CoV2 cohort in the prevaccine era., Conclusions: Our study showed that SARS-CoV2 infection is associated with an increased risk of HZ in patients with IBD., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Recombinant zoster vaccine [RZV] reduces the short-term risk of herpes zoster [HZ] in patients with inflammatory bowel disease [IBD]. However, there is lack of data regarding the long-term effectiveness in this population., Methods: A retrospective cohort study was conducted in adults ≥50 years old using TriNetX database between patients with IBD who received two doses of RZV [IBD-RZV cohort] and patients who did not receive RZV [IBD control cohort]. The primary outcome was risk of incident HZ. One-to-one propensity score matching was performed for demographic parameters, comorbid conditions, and IBD medications. Risk was expressed as adjusted odds ratio [aOR] with 95% confidence intervals [CI]., Results: The IBD-RZV cohort [n = 5489; mean age 63.2 ± 9.1 years; 57.2% females] was identified with a mean follow-up of 900.9 days. IBD-RZV cohort had a lower risk of HZ [aOR 0.44, 95% CI 0.32-0.62] compared with IBD control cohort. The risk of HZ was lower in patients aged 50-65 years [aOR 0.41, 95% CI 0.25-0.68] and patients >65 years [aOR 0.64, 95% CI 0.42-0.96]. There was a lower risk of HZ in patients with ulcerative colitis [aOR 0.41, 95% CI 0.27-0.63] and Crohn's disease [aOR 0.44, 95% CI 0.26-0.74] in the IBD-RZV cohort compared with IBD control cohort., Conclusion: RZV is associated with a lower long-term risk of HZ in patients ≥50 years old with IBD. Given the widespread availability and safety of RZV, more effective vaccination strategies are needed to improve RZV use in this high-risk population., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background and Aims: Racial and ethnic disparities exist in the treatment of IBD. These disparities exist in adult vaccine uptake among the general population and may extend to patients with IBD. The primary aim of this study was to determine whether racial, ethnic, or geographic disparities existed in influenza vaccine uptake among patients with IBD., Methods: We performed a multicenter, retrospective cohort study evaluating adult vaccine uptake among patients with IBD seen at two tertiary referral centers between September 2019 and February 2020. The primary outcome was to determine if racial/ethnic and geographic disparities existed in influenza vaccine uptake for the two prior seasons. Our secondary outcomes were to determine if disparities existed for pneumococcal, zoster, or hepatitis B vaccines., Results: Among the 2453 patients who met the inclusion criteria, most identified as non-Hispanic White (89.9%), were on immunosuppressive therapy (74.5%), and received the influenza vaccine in both seasons (56.0%). Older age (prevalence ratio (PR) 0.98; 95% confidence interval (95%CI) 0.98-0.99; P  < .001) and non-Hispanic White patients (PR 0.76, 95%CI 0.59-0.98, P  < 0.03) were significantly more likely to be immunized. Black patients (PR 1.37; 95%CI 1.18-1.59; P  < .001) and those living in underserved geographic areas (PR 1.35; 95%CI 1.17-1.56; P  < 0.001) were less likely to be immunized. Racial/ethnic and geographic disparities were identified for pneumococcal, zoster, and hepatitis B vaccine uptake., Conclusions: Racial and ethnic vaccination uptake disparities exist among patients with IBD; patients from medically underserved areas are also vulnerable to these disparities Studies identifying patient, provider, and system-level opportunities to address these disparities are needed., Competing Interests: F.C. has received research support from Takeda Pharmaceuticals. He has been a consultant for Takeda, Arena Pharmaceuticals, GSK, and Celgene. F.A.F. is a consultant for AbbVie, BMS, Braintree Labs, Fresenius Kabi, GI Reviewers, GSK, IBD Educational Group, Iterative Health, Janssen, Pharmacosmos, Pfizer,Sebela and Viatris. He sits on a DSMB for Eli Lilly. M.S.H. is a consultant for GSK Vaccines and Seqirus and has received research support from Takeda Pharmaceuticals and Dynavax. P.B.P. has been a consultant for Takeda Pharmaceuticals. Guarantor of the article: F.C., D.O., M.S. F.C.—study concept and design, acquisition of data, analysis and interpretation of data, drafting of the manuscript, and critical revision of manuscript. M.S.H—study concept and design, acquisition of data, analysis, and interpretation of data, drafting of the manuscript, and critical revision of manuscript. P.B.P.—study concept and design, acquisition of data, and interpretation of data, drafting of the manuscript, and critical revision of manuscript. G.W.—study concept and design, acquisition of data, analysis and interpretation of data, drafting of the manuscript, and critical revision of manuscript. F.A.F.—critical revision of manuscript. J.W.—study concept and design and critical revision of manuscript. K.B.—acquisition of data and critical revision of manuscript. A.U.—acquisition of data and critical revision of manuscript. T.L.S.—acquisition of data and critical revision of manuscript. R.S.—acquisition of data and critical revision of manuscript. A.H.—acquisition of data and critical revision of manuscript. L.H.—acquisition of data and critical revision of manuscript. K.E.D.—acquisition of data and critical revision of manuscript. S.D.—acquisition of data and critical revision of manuscript. N.S.—acquisition of data and critical revision of manuscript. K.R.S.—acquisition of data and critical revision of manuscript. R.K.R.—data analysis and critical revision of manuscript. M.A.M.—acquisition of data and critical revision of manuscript. F.O.—statistical analysis., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

Background: Some patients with inflammatory bowel disease (IBD) on immunosuppressive therapies may have a blunted response to certain vaccines, including the messenger RNA (mRNA) coronavirus disease 2019 (COVID-19) vaccines. However, few studies have evaluated the cell-mediated immune response (CMIR), which is critical to host defense after COVID-19 infection. The aim of this study was to evaluate the humoral immune response and CMIR after mRNA COVID-19 vaccination in patients with IBD., Methods: This prospective study (HERCULES [HumoRal and CellULar initial and Sustained immunogenicity in patients with IBD] study) evaluated humoral immune response and CMIR after completion of 2 doses of mRNA COVID-19 vaccines in 158 IBD patients and 20 healthy control (HC) subjects. The primary outcome was the CMIR to mRNA COVID-19 vaccines in patients with IBD. The secondary outcomes were a comparison of (1) the CMIR in patients with IBD and HC subjects, (2) CMIR and humoral immune response in all participants, and (3) correlation between CMIR and humoral immune response., Results: The majority (89%) of patients with IBD developed a CMIR, which was not different vs HC subjects (94%) (P = .6667). There was no significant difference (P = .5488) in CMIR between immunocompetent (median 255 [interquartile range, 146-958] spike T cells per million peripheral blood mononuclear cells) and immunosuppressed patients (median 377 [interquartile range, 123-1440]). There was no correlation between humoral and cell-mediated immunity after vaccination (P = .5215). In univariable analysis, anti-tumor necrosis factor therapy was associated with a higher CMIRs (P = .02) and confirmed in a multivariable model (P = .02). No other variables were associated with CMIR., Conclusions: Most patients with IBD achieved CMIR to a COVID-19 vaccine. Future studies are needed evaluating sustained CMIR and clinical outcomes., (© The Author(s) 2022. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The recent emergency use authorization of a third COVID-19 vaccine means that most patients with inflammatory bowel disease (IBD) will soon be eligible to be vaccinated. Gastroenterology clinicians should be prepared to address patients' concerns regarding safety and efficacy of vaccines. They should also strongly recommend that all their patients be vaccinated with a COVID-19 vaccine. Additionally, they should be prepared to educate patients about logistics that will result in successful vaccination completion. All these measures will be crucial to ensure high uptake among their patients with IBD., (© 2021 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Recent advances in the treatment of inflammatory bowel disease (IBD) include the use of immune modifiers and monoclonal antibodies, such as tumor necrosis factor (TNF) alpha inhibitors, anti-integrin agents, janus kinase inhibitors, and interleukin-12/23 inhibitors. These agents achieve higher rates of clinical remission and mucosal healing than conventional therapy. However, these therapies increase the risk of infections, including some vaccine-preventable diseases. Infections are one of the most common adverse event of immunosuppressive therapy. Thus, providers should optimize immunization strategies to reduce the risk of vaccine-preventable infections in patients with IBD. There are several newly licensed vaccines recommended for adults by the US Advisory Committee on Immunization Practices. This review will focus on how gastroenterology providers can implement the adult immunization schedule approved by ACIP for patients with IBD., (© 2020 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Patients with inflammatory bowel disease (IBD) on anti-tumor necrosis factor alpha (TNF) agents may have lower immune response to the influenza vaccine. We aimed to evaluate the immunogenicity of the high dose (HD) vs standard dose (SD) influenza vaccine in patients with IBD on anti-TNF monotherapy., Methods: We performed a randomized clinical trial at a single academic center evaluating the immunogenicity of the HD vs SD influenza vaccine in patients with IBD on anti-TNF monotherapy. Influenza antibody concentration was measured at immunization, at 2 to 4 weeks postimmunization, and at 6 months., Results: Sixty-nine patients with IBD were recruited into the study, 40 on anti-TNF monotherapy, and 19 on vedolizumab, along with 20 healthy controls (HC). Patients with IBD receiving the HD influenza vaccine had significantly higher H3N2 postimmunization antibodies compared with those who received the SD influenza vaccine (160 [interquartile range 80 to 320] vs 80 [interquartile range 40 to 160]; P = 0.003). The H1N1 postimmunization levels were not significantly higher in the HD influenza vaccine (320 [interquartile range 150 to 320] vs 160 [interquartile range 80 to 320]; P = 0.18). Patients with IBD receiving the HD influenza vaccine and those on vedolizumab who received SD had equivalent antibody concentrations to HC (H1N1 P = 0.85; H3N2 P = 0.23; B/Victoria P = 0.20 and H1N1 P = 0.46; H3N2 P = 0.21; B/Victoria P = 1.00, respectively)., Conclusions: Patients with IBD on anti-TNF monotherapy receiving the HD influenza vaccine had significantly higher postimmunization antibody levels compared with SD vaccine. Clinicaltrials.gov (#NCT02461758)., (© 2019 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Cell wall peptidoglycan stimulates interleukin 10 (IL-10) production in Staphylococcus aureus bacteremia (SaB) animal models, but clinical data are not available. This study evaluates the impact of intravascular bacterial cell numbers (ie, the level of bacteremia), in patients at the time of clinical presentation on IL-10 production and its association with S. aureus bacteremia (SaB) mortality., Methods: Blood and isolates were collected in 133 consecutive SaB patients. Serum IL-10 was quantified by an electrochemoluminescence assay. Bacterial inoculum was measured in patient sera with elevated (n = 8) or low (n = 8) IL-10 using a magnetic bacterial capture assay. Staphylococcus aureus from these 2 groups were introduced into whole blood ex vivo to determine IL-10 production with variable inocula., Results: IL-10 serum concentration was higher in SaB patient mortality (n = 27) vs survival (n = 106) (median, 36.0 pg/mL vs 10.4 pg/mL, respectively, P < .001). Patients with elevated IL-10 more often had endovascular SaB sources. The inoculum level of SaB was higher in patients with elevated serum IL-10 vs patients with low IL-10 (35.5 vs 0.5 median CFU/mL; P = .044). Ex vivo studies showed that 108 CFU/mL yielded greater IL-10 than did 103 CFU/mL (4.4 ± 1.8 vs 1.0 ± 0.6 pg/mL; P < .01)., Conclusions: Elevated IL-10 serum concentrations at clinical presentation of SaB were highly associated with mortality. High intravascular peptidoglycan concentration, driven by a higher level of bacteremia, is a key mediator of IL-10 anti-inflammatory response that portends poor clinical outcome. Using IL-10 as an initial biomarker, clinicians may consider more aggressive antimicrobials for rapid bacterial load reduction in high-risk SaB patients., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Toxins contribute to the pathogenicity of Staphylococcus aureus infections by inducing a dysregulated inflammatory response. This study evaluated the impact of anti-staphylococcal antibiotic exposures over an increasing concentration range on cytokine production from peripheral blood mononuclear cells (PBMCs) after S. aureus toxin exposures., Methods: Human PBMCs were suspended in complete Roswell Park Memorial Institute (RPMI) 1640 medium with 10% fetal bovine serum at 10(6) cells/mL with 100 ng/mL S. aureus toxic shock syndrome toxin-1 (TSST-1), staphylococcal enterotoxin A (SEA), α-toxin or Panton-Valentine leucocidin (PVL). Vancomycin, trimethoprim/sulfamethoxazole, tigecycline, daptomycin, linezolid, clindamycin and azithromycin were added at a concentration range of 0.5-100 mg/L. Cytokine [interleukin-1β (IL-1β), IL-6, IL-8, interferon-γ (IFN-γ) and tumour necrosis factor-α (TNF-α)] concentrations were measured in duplicate by ELISA following exposure and were compared with response with toxin alone., Results: At concentrations approximating serum C(max), tigecycline decreased IL-6 by 52%-57% and IFN-γ production by 43%-53% compared with toxin alone (P ≤ 0.05) and linezolid inhibited TNF-α by 12%-35% and IL-8 by 25%-42% (P ≤ 0.02). However, trimethoprim/sulfamethoxazole increased TNF-α and IL-8 production (P = 0.002). Clindamycin, daptomycin, vancomycin and azithromycin had no consistent significant effect at approximate serum C(max) concentrations. All antibiotics had a concentration-dependent effect on cytokine production, with tigecycline, clindamycin and trimethoprim/sulfamethoxazole being the most potent inhibitors of cytokine production at concentrations exceeding 25 mg/L., Conclusions: S. aureus toxins stimulate production of inflammatory cytokines in PBMCs. Antimicrobials with high tissue penetration, including tigecycline, clindamycin, trimethoprim/sulfamethoxazole and linezolid, reduced cytokine production, which, along with their antimicrobial effects, may have importance in the therapeutic outcome of severe infections.

The clinical course of smallpox infection and the current and future roles of vaccination and strategies for controlling smallpox outbreaks are reviewed. Close personal contact is required for transmission of variola, the DNA virus that causes smallpox. Following an incubation period, infected persons have prodromal symptoms that include high fever, back pain, malaise, and prostration. The eruptive stage is characterized by maculopapular rash that progresses to papules, then vesicles, and then pustules and scab lesions. The mortality rate for smallpox is approximately 30%. Patients having a fever and rash may be confused with having chickenpox. The most effective method for preventing smallpox epidemic progression is vaccination. Until recently, only 15 million doses of smallpox vaccine--manufactured 20 years ago--were available in the United States. The vaccine is a live vaccinia virus preparation administered by scarification with a bifurcated needle. The immune response is protective against orthopoxviruses, including variola. Vaccination is associated with moderate to severe complications, such as generalized vaccinia, eczema vaccinatum, progressive vaccinia, and postvaccinial encephalitis. Efforts for vaccine production are now focused on a live cell-culture-derived vaccinia virus vaccine. Although smallpox was eradicated in 1980, it remains a potential agent for bioterrorism. As a category A biological weapon, its potential to devastate populations causes concern among those in the public health community who have been actively developing plants to deal with smallpox and other potential agents of biological warfare. The only proven effective strategy against smallpox is vaccination.

The impact of pharmacogenomics on the prevention, diagnosis, and treatment of infectious diseases is discussed. The application of pharmacogenomics to infectious diseases requires consideration of the genomes of both the pathogen and the host. The pathogen's genome may be used for antigen identification, to identify infecting organisms, and to determine antimicrobial resistance. Diagnostic tool development and vaccine design can be aided by knowing which portions of a pathogen are important antigenic determinants. The unique genetic makeup of a pathogen can facilitate its identification as an augmentation to the traditional culture. Important genes conferring resistance to antibiotics can be detected, and this information can be used to choose appropriate antibiotic therapy. The genome of the host may reveal susceptibility genes and new drug targets that may be used in the treatment of infectious diseases. Thus far, polymorphisms in genes of the host immune system have been associated with susceptibility to infections and response to treatment. Examples of these findings will be described. Pharmacogenomics has the potential to revolutionize the prevention, diagnosis, and treatment of infectious diseases.