Safety and Immunogenicity of Shorter Interval Schedules of the Novel Oral Poliovirus Vaccine Type 2 in Infants

Two nOPV2 doses administered 1 week or 2 weeks apart from age 6 weeks to 8 weeks were safe and immunogenic. Immune responses after a 2-week interval were non-inferior to those after the standard 4-week interval, but marked responses after a 1-week interval suggest that schedules with an over 1-week interval can be used to provide flexibility to campaigns to improve coverage and hasten protection during circulating vaccine-derived poliovirus type 2 outbreaks.

source: The Lancet

Summary

A Phase 3, Randomised, Controlled, Non-Inferiority Study in the Dominican Republic

[Posted 4/Mar/2024]

AUDIENCE: Infectious Disease, Pediatric

KEY FINDINGS: Two nOPV2 doses administered 1 week or 2 weeks apart from age 6 weeks to 8 weeks were safe and immunogenic. Immune responses after a 2-week interval were non-inferior to those after the standard 4-week interval, but marked responses after a 1-week interval suggest that schedules with an over 1-week interval can be used to provide flexibility to campaigns to improve coverage and hasten protection during circulating vaccine-derived poliovirus type 2 outbreaks.

BACKGROUND: The novel oral poliovirus vaccine type 2 (nOPV2) is now authorised by a WHO emergency use listing and widely distributed to interrupt outbreaks of circulating vaccine-derived poliovirus type 2. As protection of vulnerable populations, particularly young infants, could be facilitated by shorter intervals between the two recommended doses, we aimed to assess safety and non-inferiority of immunogenicity of nOPV2 in 1-week, 2-week, and 4-week schedules.

DETAILS: In this phase 3, open-label, randomised trial, healthy, full-term, infants aged 6-8 weeks from a hospital or a clinic in the Dominican Republic were randomly allocated (1:1:1 ratio) using a pre-prepared, computer-generated randomisation schedule to three groups to receive two doses of nOPV2 immunisations with a 1-week interval (group A), 2-week interval (group B), or 4-week interval (group C). The nOPV2 vaccine was given at a 0.1 mL dose and contained at least 105 50% cell culture infective dose. Neutralising antibodies against poliovirus types 1, 2, and 3 were measured before each immunisation and 4 weeks after the second dose. The primary outcome was the type 2 seroconversion rate 28 days after the second dose, and the non-inferiority margin was defined as a lower bound 95% CI of greater than -10%. Safety and reactogenicity were assessed through diary cards completed by the parent or guardian. Authors enrolled 905 infants between Dec 16, 2021, and March 28, 2022. 872 infants were included in the per-protocol analyses: 289 in group A, 293 in group B, and 290 in group C. Type 2 seroconversion rates were 87.5% (95% CI 83.2 to 91.1) in group A (253 of 289 participants), 91.8% (88.1 to 94.7) in group B (269 of 293 participants), and 95.5% (92.5 to 97.6) in group C (277 of 290 participants). Non-inferiority was shown for group B compared with group C (difference in rates -3.7; 95% CI -7.9 to 0.3), but not for group A compared with group C (-8.0; -12.7 to -3.6). 4 weeks after the second nOPV2 dose, type 2 neutralising antibodies increased in all three groups such that over 95% of each group was seroprotected against polio type 2, although final geometric mean titres tended to be highest with longer intervals between doses. Immunisation with nOPV2 was well tolerated with no causal association to vaccination of any severe or serious adverse event; one death from septic shock during the study was unrelated to the vaccine.

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Source: Mejia, L. R., Mendez, L. P., Bandyopadhyay, A. S., et al. (2024). Safety and Immunogenicity of Shorter Interval Schedules of the Novel Oral Poliovirus Vaccine Type 2 in Infants: A Phase 3, Randomised, Controlled, Non-Inferiority Study in the Dominican Republic. The Lancet. 2024; 24(3): 275-284. Published: March, 2024. DOI: 10.1016/S1473-3099(23)00519-4.



Oral Linezolid Compared With Benzathine Penicillin G for Treatment of Early Syphilis in Adults (Trep-AB Study) in Spain

The efficacy of linezolid at a daily dose of 600 mg for 5 days did not meet the non-inferiority criteria compared with BPG and, as a result, this treatment regimen should not be used to treat patients with early syphilis.

source: The Lancet

Summary

A Prospective, Open-Label, Non-Inferiority, Randomised Controlled Trial

[Posted 8/Apr/2024]

AUDIENCE: Infectious Disease, Family Medicine

KEY FINDINGS: The efficacy of linezolid at a daily dose of 600 mg for 5 days did not meet the non-inferiority criteria compared with BPG and, as a result, this treatment regimen should not be used to treat patients with early syphilis.

BACKGROUND: Management of syphilis, a sexually transmitted infection (STI) with increasing incidence, is challenged by drug shortages, scarcity of randomised trial data, an absence of non-penicillin alternatives for pregnant women with penicillin allergy (other than desensitisation), extended parenteral administration for neurosyphilis and congenital syphilis, and macrolide resistance. Linezolid was shown to be active against Treponema pallidum, the causative agent of syphilis, in vitro and in the rabbit model. We aimed to assess the efficacy of linezolid for treating early syphilis in adults compared with the standard of care benzathine penicillin G (BPG).

DETAILS: Authors did a multicentre, open-label, non-inferiority, randomised controlled trial to assess the efficacy of linezolid for treating early syphilis compared with BPG. Authors recruited participants with serological or molecular confirmation of syphilis (either primary, secondary, or early latent) at one STI unit in a public hospital and two STI community clinics in Catalonia (Spain). Participants were randomly allocated in a 1:1 ratio using a computer-generated block randomisation list with six participants per block, to receive either oral linezolid (600 mg once per day for 5 days) or intramuscular BPG (single dose of 2.4 million international units) and were assessed for signs and symptoms (once per week until week 6 and at week 12, week 24, and week 48) and reagin titres of non-treponemal antibodies (week 12, week 24, and week 48). The primary endpoint was treatment response, assessed using a composite endpoint that included clinical response, serological response, and absence of relapse. Clinical response was assessed at 2 weeks for primary syphilis and at 6 weeks for secondary syphilis following treatment initiation. Serological cure was defined as a four-fold decline in rapid plasma reagin titre or seroreversion at any of the 12-week, 24-week, or 48-week timepoints. The absence of relapse was defined as the presence of different molecular sequence types of T pallidum in recurrent syphilis. Non-inferiority was shown if the lower limit of the two-sided 95% CI for the difference in rates of treatment response was higher than -10%. The primary analysis was done in the per-protocol population. The trial is registered at ClinicalTrials.gov (NCT05069974) and was stopped for futility after interim analysis. Between Oct 20, 2021, and Sept 15, 2022, 62 patients were assessed for eligibility, and 59 were randomly assigned to linezolid (n=29) or BPG (n=30). In the per-protocol population, after 48 weeks' follow-up, 19 (70%) of 27 participants (95% CI 49.8 to 86.2) in the linezolid group had responded to treatment and 28 (100%) of 28 participants (87.7 to 100.0) in the BPG group (treatment difference -29.6, 95% CI -50.5 to -8.8), which did not meet the non-inferiority criterion. The number of drug-related adverse events (all mild or moderate) was similar in both treatment groups (five [17%] of 29, 95% CI 5.8 to 35.8 in the linezolid group vs five [17%] of 30, 5.6 to 34.7, in the BPG group). No serious adverse events were reported during follow-up.

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Source: Ubals, M., Nadal-Baron, P., Arando, M., et al. (2024). Oral Linezolid Compared With Benzathine Penicillin G for Treatment of Early Syphilis in Adults (Trep-AB Study) in Spain: A Prospective, Open-Label, Non-Inferiority, Randomised Controlled Trial. The Lancet. 2024; 24(4): 404-416. Published: April, 2024. DOI: 10.1016/S1473-3099(23)00683-7.



Exploring the Interrelationships Between Physical Function, Functional Exercise Capacity, and Exercise Self-Efficacy in Persons Living with HIV

While physical activity can mitigate the metabolic effects of HIV disease and HIV medications, many HIV-infected persons report low levels of physical activity.

source: Clinical Nursing Research

Summary

[Posted 12/Mar/2024]

AUDIENCE: Nursing

KEY FINDINGS: Making Time for Exercise Self-efficacy was more significant than Resisting Relapse for both physical function and functional exercise capacity. Interventions to promote achievement of physical activity need to use multiple measurement strategies.

BACKGROUND: Objective of this study is to determine if there were differences between the subjective and objective assessments of physical activity while controlling for sociodemographic, anthropometric, and clinical characteristics. A total of 810 participants across eight sites located in three countries. Both univariate and multivariant analyses were used.

DETAILS: Subjective instruments were the two subscales of Self-efficacy for Exercise Behaviors Scale: Making Time for Exercise and Resisting Relapse and Patient-Reported Outcomes Measurement Information System, which measured physical function. The objective measure of functional exercise capacity was the 6-minute Walk. Physical function was significantly associated with Making Time for Exercise (β = 1.76, p = .039) but not with Resisting Relapse (β = 1.16, p = .168). Age (β = -1.88, p = .001), being employed (β = 16.19, p < .001) and race (βs = 13.84–31.98, p < .001), hip–waist ratio (β = -2.18, p < .001), and comorbidities (β = 7.31, p < .001) were significant predictors of physical functioning. The model predicting physical function accounted for a large amount of variance (adjusted R2 = .938). The patterns of results predicting functional exercise capacity were similar. Making Time for Exercise self-efficacy scores significantly predicted functional exercise capacity (β = 0.14, p = .029), and Resisting Relapse scores again did not (β = -0.10, p = .120). Among the covariates, age (β = -0.16, p < .001), gender (β = -0.43, p < .001), education (β = 0.08, p = .026), and hip–waist ratio (β = 0.09, p = .034) were significant. This model did not account for much of the overall variance in the data (adjusted R2 = .081). We found a modest significant relationship between physical function and functional exercise capacity (r = 0.27).

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Source: Nokes, K. M., Sokhela, D. G., Orton, P, M., et al. (2024). Exploring the Interrelationships Between Physical Function, Functional Exercise Capacity, and Exercise Self-Efficacy in Persons Living with HIV. XXXXXXXX. 2024; 33(2-3): 165-175. Published: March, 2024. DOI: 10.1177/10547738241231626.



Prior Herpes Simplex Virus Infection and the Risk of Herpes Zoster

The study demonstrated that prior infection with HSV partly protects against HZ.

source: J Infect Disease

Summary

[Posted 6/Feb/2024]

AUDIENCE: Infectious Disease, Internal Medicine

KEY FINDINGS: The study demonstrated that prior infection with HSV partly protects against HZ.

BACKGROUND: The incidence of herpes zoster (HZ) has increased in the United States concurrent with decrease in herpes simplex virus (HSV) prevalence. Authors hypothesized that lack of HSV-elicited cross-reactive immunity to varicella-zoster virus (VZV) results in an increased risk of HZ. Using specimens from the placebo arm of the Shingles Prevention Study, authors investigated whether persons who develop HZ are less likely to have prior HSV infection than persons who do not develop HZ, and whether HZ is less severe in persons with HSV than in HSV seronegative persons.

DETAILS: Authors conducted a nested case-control (1:2) study comparing the seroprevalence of HSV-1 and HSV-2 in cases (persons with polymerase chain reaction-confirmed HZ) to age-, sex-, and health-matched controls (persons without HZ). Sera from 639 study participants (213 cases and 426 controls) yielded definitive HSV antibody results and were analyzed. Overall, HSV seropositivity rate was 75%. HSV seronegativity was significantly higher in HZ cases than controls (30.5% vs 22.3%; P = .024), with a 55% higher risk of HZ in HSV seronegative than HSV seropositive participants. HSV seropositivity was associated with more severe HZ (P = .021).

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Source: Harbecke, R., Oxman, M. N., Selke, S., et al. (2024). Prior Herpes Simplex Virus Infection and the Risk of Herpes Zoster. The Journal of Infectious Diseases. 2024; 229(1): 64-72. Published: January 15, 2024. DOI: 10.1093/infdis/jiad259.



Safety and Immunogenicity of an Andes Virus DNA Vaccine by Needle-Free Injection

This first-in-human candidate HPS vaccine trial demonstrated that an ANDV DNA vaccine was safe and induced a robust, durable immune response.

source: J Infect Disease

Summary

A Randomized, Controlled Phase 1 Study

[Posted 22/Jan/2024]

AUDIENCE: Infectious Disease, Internal Medicine

KEY FINDINGS: This first-in-human candidate HPS vaccine trial demonstrated that an ANDV DNA vaccine was safe and induced a robust, durable immune response.

BACKGROUND: Andes virus (ANDV), a rodent-borne hantavirus, causes hantavirus pulmonary syndrome (HPS). The safety and immunogenicity of a novel ANDV DNA vaccine was evaluated.

DETAILS: Phase 1, double-blind, dose-escalation trial randomly assigned 48 healthy adults to placebo or ANDV DNA vaccine delivered via needle-free jet injection. Cohorts 1 and 2 received 2 mg of DNA or placebo in a 3-dose (days 1, 29, 169) or 4-dose (days 1, 29, 57, 169) schedule, respectively. Cohorts 3 and 4 received 4 mg of DNA or placebo in the 3-dose and 4-dose schedule, respectively. Subjects were monitored for safety and neutralizing antibodies by pseudovirion neutralization assay (PsVNA50) and plaque reduction neutralization test (PRNT50). While 98% and 65% of subjects had at least 1 local or systemic solicited adverse event (AE), respectively, most AEs were mild or moderate; no related serious AEs were detected. Cohorts 2, 3, and 4 had higher seroconversion rates than cohort 1 and seropositivity of at least 80% by day 197, sustained through day 337. PsVNA50 geometric mean titers were highest for cohort 4 on and after day 197.

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Source: Paulsen, G. C., Frenck, R., Tomashek, K. M., et al. (2024). Safety and Immunogenicity of an Andes Virus DNA Vaccine by Needle-Free Injection: A Randomized, Controlled Phase 1 Study . Journal of Infectious Diseases. 2024; 229(1): 30-38. Published: January 15, 2024. DOI: 10.1093/infdis/jiad235.



Nonsecretor Phenotype Is Associated With Less Risk of Rotavirus-Associated Acute Gastroenteritis in a Vaccinated Nicaraguan Birth Cohort

The nonsecretor phenotype was associated with decreased risk of clinical rotavirus vaccine failure in a vaccinated Nicaraguan birth cohort. These results show the importance of secretor status on rotavirus risk, even in vaccinated children.

source: J Infect Disease

Summary

[Posted 8/Jan/2024]

AUDIENCE: Infectious Disease, Pediatric, Internal Medicine

KEY FINDINGS: The nonsecretor phenotype was associated with decreased risk of clinical rotavirus vaccine failure in a vaccinated Nicaraguan birth cohort. These results show the importance of secretor status on rotavirus risk, even in vaccinated children.

BACKGROUND: Histo-blood group antigens (HBGAs) have been associated with rotavirus vaccine take; but the effect of these HBGAs on rotavirus incidence and risk remains poorly explored in vaccinated populations.

DETAILS: Rotavirus-associated acute gastroenteritis (AGE) was assessed in 444 Nicaraguan children followed from birth until 3 years of age. AGE episodes were tested for rotavirus by reverse-transcription quantitative polymerase chain reaction, and saliva or blood was used to determine HBGA phenotypes. Cox proportional hazards models were used to estimate the relative hazard of rotavirus AGE by HBGA phenotypes. Rotavirus was detected in 109 (7%) stool samples from 1689 AGE episodes over 36 months of observation between June 2017 and July 2021. Forty-six samples were successfully genotyped. Of these, 15 (35%) were rotavirus vaccine strain G1P[8], followed by G8P[8] or G8P[nt] (11 [24%]) and equine-like G3P[8] (11 [24%]). The overall incidence of rotavirus-associated AGE was 9.2 per 100 child-years, and was significantly higher in secretor than nonsecretor children (9.8 vs 3.5/100 child-years, P = .002).

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Copyright © Oxford University Press for the Infectious Diseases Society of America. All rights reserved.

Source: Reyes, Y., St Jean, D. T., Bowman, N. M., et al. (2023). Nonsecretor Phenotype Is Associated With Less Risk of Rotavirus-Associated Acute Gastroenteritis in a Vaccinated Nicaraguan Birth Cohort. The Journal of Infectious Diseases. 2023; 28(12): 1739-1747. Published: December 15, 2023. DOI: 10.1093/infdis/jiad202.



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