Seroresponse to third doses of SARS-CoV-2 vaccine among patients receiving maintenance dialysis

Given the increased morbidity and mortality from COVID-19 among patients undergoing maintenance dialysis, we examined the seroresponse to an additional dose of SARS-CoV-2 mRNA vaccine, using a hypothesized protective anti-spike protein IgG antibody threshold of 7 based on prior work. Among 395 patients, 384 (97%) had seroresponse ≥7 following administration of the third dose. Among those with suboptimal (peak <7) and minimal (peak <1) seroresponse to an initial mRNA vaccine regimen, the rate of seroresponse ≥7 following a third dose was 97% (36 of 37) and 64% (14 of 22), respectively. Given ongoing high rates of COVID-19 and rapidly waning immunity after an initial vaccine series, we recommend a third mRNA vaccine dose be standard for all patients receiving maintenance dialysis.

Humoral immune responses against SARS-CoV-2 variants including omicron in solid organ transplant recipients after three doses of a COVID-19 mRNA vaccine

BACKGROUND: Solid organ transplant recipients (SOTR), who typically receive post-transplant immunosuppression, show increased COVID-19-related mortality. It is unclear whether an additional dose of COVID-19 vaccines in SOTR can overcome the reduced immune responsiveness against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants. METHODS: We performed a prospective cohort study of 53 SOTR receiving SARS-CoV-2 vaccination into a prospective cohort study performing detailed immunoprofiling of humoral immune responses against SARS-CoV-2 and its variants. RESULTS: Prior to the additional vaccine dose, 60.3% of SOTR showed no measurable neutralization and only 18.9% demonstrated neutralizing activity of >90% following two vaccine doses. More intensive immunosuppression, antimetabolites in particular, negatively impacted antiviral immunity. While absolute IgG levels were lower in SOTR than controls, antibody titers against microbial recall antigens were in fact higher. In contrast, SOTR showed reduced vaccine-induced IgG/IgA antibody titers against SARS-CoV-2 and its delta variants. Vaccinated SOTR showed a markedly fewer linear B cell epitopes, indicating reduced B cell diversity. Importantly, a third vaccine dose led to an increase in anti-SARS-CoV-2 antibody titers and neutralizing activity across alpha, beta and delta variants. However, we observed a significant decrease in anti-spike antibody titers with the omicron variant. CONCLUSIONS: Only a small subgroup of SOTR generated functionally relevant antibodies after completing the initial vaccine series based on dysfunctional priming of immune responses against novel antigens. An additional dose of the vaccine results in dramatically improved antibody responses against all SARS-CoV-2 variants except omicron.

Epidemiology of mumps outbreaks and the impact of an additional dose of MMR vaccine for outbreak control in regional Queensland, Australia, 2017–2018

Background In recent years, there have been ongoing outbreaks of mumps reported in Northern and North-Western Queensland, Western Australia and the Northern Territory, Australia. We aimed to define the epidemiology of mumps outbreaks in Central Queensland, Australia between October 2017 and October 2018 and evaluate the effectiveness of an additional dose of measles, mumps, rubella (MMR) vaccine. Methods A retrospective case control study was conducted, including outbreak investigations with laboratory-confirmed cases of mumps and subsequent comparison with matched controls. We analysed mandatory notifications from the Queensland Health Notifiable Conditions System database and immunisation information from the Queensland Health Vaccination Information and Admin System (VIVAS) and the Australian Immunisation Register. Results Between October 2017 and October 2018, there were 93 cases of mumps reported in Central Queensland with three distinct outbreaks: a discrete Indigenous community; a correctional facility; and a boarding school. Among all cases, 74 (79.6%) were fully vaccinated and 14 (15.1%) were partially vaccinated with MMR vaccine. Eighty-six cases (92.5%) were reported among Aboriginal and Torres Strait Islander people. In all outbreaks, an additional dose of MMR vaccine was offered with 35.4%, 73.6% and 35.8% of the target population being immunised in the discrete Indigenous community, the correctional facility and the boarding school, respectively. Prior to this additional dose of MMR, the mumps attack rate was 31.0 (95% confidence interval [95% CI]: 24.2–39.0) per 1000 population, compared to the post-additional dose MMR attack rate of 10.6 (95% CI: 6.7–15.9) per 1000 population. Conclusion An additional or booster dose of MMR should be included as an effective public health intervention strategy, particularly in communal or high-density living conditions to control mumps outbreaks in highly vaccinated populations.

Comparative effectiveness of allocation strategies of COVID-19 vaccines and antivirals against emerging SARS-CoV-2 variants of concern in East Asia and Pacific region

Background We aimed to evaluate the impact of various allocation strategies of COVID-19 vaccines and antiviral such that the pandemic exit strategy could be tailored to risks and preferences of jurisdictions in the East Asia and Pacific region (EAP) to improve its efficiency and effectiveness. Methods Vaccine efficacies were estimated from the titre distributions of 50% plaque reduction neutralization test (PRNT50), assuming that PRNT50 titres of primary vaccination decreased by 2-10 folds due to antibody waning and emergence of VOCs, and an additional dose of vaccine would increase PRNT50 titres by 3- or 9-fold. We then used an existing SARS-CoV-2 transmission model to assess the outcomes of vaccine allocation strategies with and without the use of antivirals for symptomatic patients in Japan, Hong Kong and Vietnam. Findings Increasing primary vaccination coverage was the most important contributing factor in reducing the total and peak number of COVID-19 hospitalizations, especially when population vaccine coverage or vaccine uptake among older adults was low. Providing antivirals to 50% of symptomatic infections only further reduced total and peak hospitalizations by 10-13%. The effectiveness of an additional dose of vaccine was highly dependent on the immune escape potential of VOCs and antibody waning, but less dependent on the boosting efficacy of the additional dose. Interpretation Increasing primary vaccination coverage should be prioritised in the design of allocation strategies of COVID-19 vaccines and antivirals in the EAP region. Heterologous vaccination with any available vaccine as the additional dose could be considered when planning pandemic exit strategies tailored to the circumstances of EAP jurisdictions.

The use of sugammadex in an infant with prolonged neuromuscular blockade - A case report -

Background: Residual neuromuscular blockade (RNMB) is a frequent event after general anesthesia, which can lead to serious complications, such as upper airway obstruction. Sugammadex is useful in reversing RNMB. However, its use in infants has not yet been approved by the Food and Drug Administration. Therefore, anesthesiologists can be hesitant use it, even in situations where no other choice is available.Case: A two-month-old baby presented to the hospital for umbilical polypectomy. At the end of the surgery, neostigmine was administered. Even after waiting for 30 min and injecting an additional dose of neostigmine, neuromuscular blockade was not adequately reversed. Eventually, sugammadex was administered, and spontaneous breathing returned.Conclusions: If there were no particular causes of delayed return to spontaneous breathing in infants, RNMB should be considered and reversal with sugammadex would be useful.

Immunogenicity of a third scheduled dose of rotavirus vaccine in Australian Indigenous infants to improve protection against gastroenteritis: a phase IV, double-blind, randomised, placebo-controlled clinical trial

BackgroundThe oral rotavirus vaccine, Rotarix (GlaxoSmithKline), is licensed for use in infants as two doses in the first six months of life. For infants living in settings with high child-mortality, and also for rural and remote Australian Aboriginal infants, clinical protection conferred by two doses of Rotarix appears to be reduced. We assessed the effect of an additional dose of Rotarix on vaccine immune responses among Aboriginal children who are 6 to < 12 months old.MethodsORVAC is a two-stage, double-blind, randomised, placebo-controlled trial conducted across regional urban and remote locations of Australia’s Northern Territory. Aboriginal children 6 to < 12 months old who had received one or two prior doses of Rotarix were randomised 1:1 to receive an additional dose of Rotarix or matched placebo. The primary immunological endpoint was seroresponse defined as an anti-rotavirus IgA level ≥ 20 AU/mL, approximately one month following Rotarix or placebo. ClinicalTrials.gov (NCT02941107).FindingsBetween March 2018 and August 2020, 253 infants were enrolled. Of these, 178 infants (70%) had analysable serological results after follow-up; 89 randomised to Rotarix and 89 to placebo. The proportion with a seroresponse was 85% after Rotarix compared to 71% after placebo; the probability of a higher rate of seroresponse in the Rotarix than the placebo arm was 99%. There were no occurrences of intussusception or any serious adverse events attributed to Rotarix or placebo in the 28 days following the additional dose of Rotarix or placebo.InterpretationAn additional dose of Rotarix among Australian Aboriginal infants 6 to < 12 months old increased the proportion with a vaccine seroresponse. If it can be proven that this translates into better protection against disease, scheduling an additional dose may be a viable strategy for further reducing the global burden of rotavirus disease.FundingNHMRC (GNT1086952).Research in contextEvidence before this studyRotavirus vaccine programs have reduced the global burden of gastroenteritis disease among young children, but rotavirus still causes >200,000 child deaths each year. A recent systematic review in the Lancet Global Health found that the effectiveness of oral rotavirus vaccines is variable, from 45 – 58% in settings with high child mortality to 83%-85% in settings with low child mortality. In high child mortality settings there is also evidence of waning effectiveness after 12 months old. Reduced vaccine effectiveness has also been reported among Australian Aboriginal children. Previous trials have failed to demonstrate improved rotavirus vaccine effectiveness with strategies such as withholding breastfeeding, or co-administering vaccines with probiotics or zinc. Pre-licensure studies of Rotarix in Africa did not clearly indicate whether a three-dose Rotarix schedule had benefit over a two-dose schedule, although all vaccine doses were given before infants were six months old when maternal antibodies may impede vaccine responses. Trials in Bangladesh and Mali found that a third Rotarix dose given after 6 months old improved the immune response to vaccine.Added value of this studyIn the first stage of our novel two-stage randomised clinical trial, we showed that scheduling an additional Rotarix dose for remote Australian Aboriginal infants after 6 months old increased the proportion with evidence of vaccine seroresponse.Implications of all the available evidenceScheduling an additional dose of Rotarix after 6 months old is feasible, and trials in three settings have now demonstrated that it improves immune responses. Trials should now be conducted in a number of high burden settings to determine whether this strategy results in improved clinical protection against severe gastroenteritis.

Effect of retardant admixtures type and their using method on the behavior of concrete

Construction sites may be exposed to crisis conditions during the casting process, resulting in delays of several hours and causing destruction of ready-mix concrete. This study suggests an experimental analysis of the possibility of using a specific additional dose of retardant admixtures, which may be used to ready-mix concrete before the initial setting of the concrete occurs. The effect of this additional dose on concrete characteristics in terms of workability, setting time, and compressive strength is also being studied. To conduct this investigation, three types of retardant admixtures from three branded companies were used. In addition, a penetration resistance experiment was conducted on the concrete to determine its setting time. The setting time of concrete was measured at different period intervals depending on when the additional dose of the retardant admixtures was added from the start of the concrete mixing. The results showed that concrete maintained proper workability for a period of more than 5 hours after using the additional dose of retarding admixtures. The additional dose of retarding admixtures not only delayed the concrete setting but also improved the compressive strength of the concrete. This implies that the use of an additional dose of retardant admixtures specifically tailored for ready-mix concrete is an effective option to avoid the return of ready-mixed fresh concrete.

Population Pharmacokinetics of Colistin Methanesulfonate Sodium and Colistin in Critically Ill Patients: A Systematic Review

Understanding the pharmacokinetics parameter of colistin methanesulfonate sodium (CMS) and colistin is needed to optimize the dosage regimen in critically ill patients. However, there is a scarcity of pharmacokinetics parameters in this population. This review provides a comprehensive understanding of CMS and colistin pharmacokinetics parameters in this population. The relevant studies published in English that reported on the pharmacokinetics of CMS and colistin from 2000 until 2020 were systematically searched using the PubMed and Scopus electronic databases. Reference lists of articles were reviewed to identify additional studies. A total of 252 citation titles were identified, of which 101 potentially relevant abstracts were screened, and 25 full-text articles were selected for detailed analysis. Of those, 15 studies were included for the review. This review has demonstrated vast inter-study discrepancies in colistin plasma concentration and the pharmacokinetics parameter estimates. The discrepancies might be due to complex pathophysiological changes in the population studied, differences in CMS brand used, methodology, and study protocol. Application of loading dose of CMS and an additional dose of CMS after dialysis session was recommended by some studies. In view of inter-patient and intra-patient variability in colistin plasma concentration and pharmacokinetics parameters, personalized colistin dosing for this population is recommended.