Utilising Integrated Bio-behavioural Surveillance (IBBS) to investigate declining hepatitis C antibody prevalence among people who inject drugs in the Australian Needle and Syringe Program Survey.

BACKGROUND: Prevalence of hepatitis C virus (HCV) antibody (Ab) on dried blood spot (DBS) samples in the Australian Needle and Syringe Program Survey (ANSPS) decreased nationally from 57% in 2015 to 32% in 2022. We aimed to investigate potential explanations for this decline. METHODS: Changes in DBS HCV Ab prevalence were investigated by redefining positive cases as those with those with either a positive HCV Ab test result or a self-reported history of ever having HCV treatment (modified prevalence), examining HCV Ab prevalence by birth and age cohorts, and assessing trends in key risk behaviours. RESULTS: Overall prevalence of DBS HCV Ab declined rapidly and significantly from 57% in 2015 to 32% in 2022 (p<0.001) however modified HCV Ab prevalence remained stable over time (85% and 88% in 2015 and 2022, respectively, p=0.357). The proportion of participants with negative HCV Ab and self-reported HCV infection increased from 20% in 1995 to 40% in 2022 (p<0.001) and the proportion with negative HCV Ab and lifetime HCV treatment increased from 3% in 1999 to 67% in 2022 (p<0.001). We also observed a decreasing trend in DBS HCV Ab prevalence in all birth and age cohorts with a noticeable acceleration in the decline commensurate with the advent of HCV DAA treatment. A long-term decreasing trend was also observed for key risk behaviours (p<0.001) however the short-term trend was not significant for recent receptive syringe sharing. CONCLUSION: The temporal decline in HCV Ab prevalence appears related to reduced sensitivity of DBS HCV Ab detection with viral clearance following treatment. Since 2016, HCV treatment uptake has increased markedly including among people who inject drugs. In this context, continuing to monitor HCV Ab prevalence by DBS testing is problematic, with a shift to surveillance of active infection the most relevant to guide policy and practice in this setting.

Post-vaccination, post-infection and hybrid immunity against severe cases of COVID-19 and long COVID after infection with SARS-CoV-2 Omicron subvariants, Czechia, December 2021 to August 2023.

BackgroundCOVID-19 remains a major infectious disease with substantial implications for individual and public health including the risk of a post-infection syndrome, long COVID. The continuous changes in dominant variants of SARS-CoV-2 necessitate a careful study of the effect of preventative strategies.AimWe aimed to estimate the effectiveness of post-vaccination, post-infection and hybrid immunity against severe cases requiring oxygen support caused by infections with SARS-CoV-2 variants BA1/2 and BA4/5+, and against long COVID in the infected population and their changes over time.MethodsWe used a Cox regression analysis with time-varying covariates and calendar time and logistic regression applied to national-level data from Czechia from December 2021 until August 2023.ResultsRecently boosted vaccination, post-infection and hybrid immunity provide significant protection against a severe course of COVID-19, while unboosted vaccination more than 10 months ago has a negligible protective effect. The post-vaccination immunity against the BA1/2 or BA4/5+ variants, especially based on the original vaccine types, appears to wane rapidly compared with post-infection and hybrid immunity. Once infected, however, previous immunity plays only a small protective role against long COVID.ConclusionVaccination remains an effective preventative measure against a severe course of COVID-19 but its effectiveness wanes over time thus highlighting the importance of booster doses. Once infected, vaccines may have a small protective effect against the development of long COVID.

Development and implementation of evidence-based, nurse-leading early warning model and healthcare quality improvement project for transplant-associated thrombotic microangiopathy: a mixed-methods, before-and-after study.

OBJECTIVE: The early identification and diagnosis of transplant-associated thrombotic microangiopathy (TA-TMA) are essential yet difficult in patients underwent hematopoietic stem cell transplantation (HSCT). To develop an evidence-based, nurse-leading early warning model for TA-TMA, and implement the healthcare quality review and improvement project. METHODS: This study was a mixed-methods, before-and-after study. The early warning model was developed based on quality evidence from literature search. The healthcare quality review and improvement project mainly included baseline investigation of nurse, improvement action and effectiveness evaluation. The awareness and knowledge of early parameter of TA-TMA among nurses and the prognosis of patients underwent HSCT were compared before and after the improvement. RESULTS: A total of 1 guideline, 1 evidence synthesis, 4 expert consensuses, 10 literature reviews, 2 diagnostic studies, and 9 case series were included in the best evidence. The early warning model including warning period, high-risk characteristics and early manifestation of TA-TMA was developed. The improvement action, including staff training and assessment, suspected TA-TMA identification and patient education, was implemented. The awareness and knowledge rate of early parameter of TA-TMA among nurses significantly improved after improvement action (100% vs. 26.7%, P < 0.001). The incidence of TA-TMA was similar among patients underwent HSCT before and after improvement action (2.8% vs. 1.2%, P = 0.643), while no fall event occurred after improvement action (0 vs. 1.2%, P < 0.001). CONCLUSION: The evidence-based early warning model and healthcare quality improvement project could enhance the awareness and knowledge of TA-TMA among healthcare providers and might improve the prognosis of patients diagnosed with TA-TMA.

Household transmission of Omicron variant of SARS-CoV-2 under conditions of hybrid immunity-a prospective study in Germany.

PURPOSE: We investigated the protection offered by vaccinations and previous infections for the household transmission of Omicron variant of SARS-CoV-2. METHODS: 34,666 participants of the German DigiHero cohort study with two or more household members were invited to a prospective household transmission study between June and December 2022. In case of a positive SARS-CoV-2 test in a household, symptom diaries were completed for at least 14 days. Dry blood spots (DBS) were taken from all household members at the beginning and six to eight weeks later. DBS were analyzed for SARS-CoV-2 antibodies. RESULTS: 1191 individuals from 457 households participated. The risk of acquiring a SARS-CoV-2 infection decreased with higher S-titer levels at the time of exposure (from 80% at titer of 0 binding antibody units (BAU)/ml to 20% at titer of 3000 BAU/ml) and increased linearly with the time since vaccination/previous infection (20% for less than one month to 80% at one year). Transmission probability was also reduced when the symptoms of the primary case were mild and if preventive measures were implemented. CONCLUSION: Vaccinations/previous infections offer a high protection against infection with the Omicron variant for a few months only, supporting the notion of seasonal circulation of the virus.

The Problem with Delaying Measles Elimination.

Measles is a highly infectious disease leading to high morbidity and mortality impacting people's lives and economies across the globe. The measles vaccine saves more lives than any other vaccine in the Essential Programme of Immunization and is also the most cost-effective vaccine, with an extremely high return on investment. This makes achieving measles elimination through vaccination a key child health intervention, particularly in low-income countries, where the overwhelming majority of measles deaths continue to occur. All countries and regions of the world have committed to achieving measles elimination, yet many have faced challenges securing political commitment at national and global levels and predictable, timely, and flexible support from global donors, and experienced setbacks during the COVID-19 pandemic. This has happened against a backdrop of stagnant measles vaccination coverage and declining enthusiasm for vertical programmes, culminating in a World Health Organization Strategic Advisory Group of Experts (WHO SAGE) review of the feasibility of measles eradication in 2019. Sustaining the elimination of measles long term is extremely difficult, and some countries have lost or nearly lost their measles elimination status in the face of ongoing importation of cases from neighbouring or closely connected countries in which elimination had been delayed. Thus, a widening equity gap in measles immunisation coverage creates challenges for all countries, not just those facing the greatest burden of measles morbidity and mortality. Delaying elimination of measles in some countries makes it cumulatively harder for all countries to succeed for three principal reasons: increased inequity in measles immunisation coverage makes outbreaks more likely to happen and to be larger; political will is very difficult to sustain; and immunity may wane to a point that transmission is re-established. New strategies are needed to support countries and regions in their vision for a world without measles, including ways to galvanise domestic, regional and global resources and ignite the political will that is essential to make the vision a reality.

The impact of Zika emergence in remote communities in northwestern Ecuador.

The Zika virus (ZIKV) epidemic in Latin America (2015-2016) has primarily been studied in urban centers, with less understanding of its impact on smaller rural communities. To address this gap, we analyzed ZIKV sero-epidemiology in six rural Ecuadorian communities (2018-2019) with varying access to a commercial hub. Seroprevalence ranged from 19% to 54% measured by NS1 blockade of binding ELISA. We observed a decline in ZIKV seroprevalence between 2018 and 2019 that was greater among younger populations, suggesting that the attack rates in the 2015-16 epidemic were significantly higher than our 2018 observations. These data indicate that the 2015-16 epidemic included significant transmission in rural and more remote settings. Our observations of high seroprevalence in our area of study highlights the importance of surveillance and research in rural areas lacking robust health systems to manage future Zika outbreaks and vaccine initiatives.

Differences in virus and immune dynamics for SARS-CoV-2 Delta and Omicron infections by age and vaccination histories.

Vaccination against COVID-19 was integral to controlling the pandemic that persisted with the continuous emergence of SARS-CoV-2 variants. Using a mathematical model describing SARS-CoV-2 within-host infection dynamics, we estimate differences in virus and immunity due to factors of infecting variant, age, and vaccination history (vaccination brand, number of doses and time since vaccination). We fit our model in a Bayesian framework to upper respiratory tract viral load measurements obtained from cases of Delta and Omicron infections in Singapore, of whom the majority only had one nasopharyngeal swab measurement. With this dataset, we are able to recreate similar trends in URT virus dynamics observed in past within-host modelling studies fitted to longitudinal patient data.We found that Omicron had higher R0,within values than Delta, indicating greater initial cell-to-cell spread of infection within the host. Moreover, heterogeneities in infection dynamics across patient subgroups could be recreated by fitting immunity-related parameters as vaccination history-specific, with or without age modification. Our model results are consistent with the notion of immunosenescence in SARS-CoV-2 infection in elderly individuals, and the issue of waning immunity with increased time since last vaccination. Lastly, vaccination was not found to subdue virus dynamics in Omicron infections as well as it had for Delta infections.This study provides insight into the influence of vaccine-elicited immunity on SARS-CoV-2 within-host dynamics, and the interplay between age and vaccination history. Furthermore, it demonstrates the need to disentangle host factors and changes in pathogen to discern factors influencing virus dynamics. Finally, this work demonstrates a way forward in the study of within-host virus dynamics, by use of viral load datasets including a large number of patients without repeated measurements.

SIRS epidemics with individual heterogeneity of immunity waning.

In the current paper we analyse an extended SIRS epidemic model in which immunity at the individual level wanes gradually at exponential rate, but where the waning rate may differ between individuals, for instance as an effect of differences in immune systems. The model also includes vaccination schemes aimed to reach and maintain herd immunity. We consider both the informed situation where the individual waning parameters are known, thus allowing selection of vaccinees being based on both time since last vaccination as well as on the individual waning rate, and the more likely uninformed situation where individual waning parameters are unobserved, thus only allowing vaccination schemes to depend on time since last vaccination. The optimal vaccination policies for both the informed and uniformed heterogeneous situation are derived and compared with the homogeneous waning model (meaning all individuals have the same immunity waning rate), as well as to the classic SIRS model where immunity at the individual level drops from complete immunity to complete susceptibility in one leap. It is shown that the classic SIRS model requires least vaccines, followed by the SIRS with homogeneous gradual waning, followed by the informed situation for the model with heterogeneous gradual waning. The situation requiring most vaccines for herd immunity is the most likely scenario, that immunity wanes gradually with unobserved individual heterogeneity. For parameter values chosen to mimic COVID-19 and assuming perfect initial immunity and cumulative immunity of 12 months, the classic homogeneous SIRS epidemic suggests that vaccinating individuals every 15 months is sufficient to reach and maintain herd immunity, whereas the uninformed case for exponential waning with rate heterogeneity corresponding to a coefficient of variation being 0.5, requires that individuals instead need to be vaccinated every 4.4 months.

Treatment Effect Waning Assumptions: A Review of National Institute of Health and Care Excellence Technology Appraisals.

OBJECTIVES: This study aims to review the National Institute of Health and Care Excellence (NICE) technology assessments to gain insights into the implementation of treatment effect (TE) waning, whereby the hazard or survival in an assessed technology converges to that of the comparator. This analysis aims to contribute to inform future guidance in this area. METHODS: Technology appraisals published October 20, 2021 to September 20, 2023 were reviewed and data extracted on TE waning circumstances, methods, and rationale to compile a database based on 3 research questions: When are TE waning assumptions used? What methods are used? Why have the company/Evidence Assessment Group/committee preferred these methods? RESULTS: Both the evidence assessment group/company and the committee included TE waning assumptions in 28 appraisals. There was no pattern of waning assumptions between shorter (<20 years) and longer (>20 years) time horizons. The most prominent time point for applying waning assumptions was at 5 years, with 30 out of 59 (50.8%) of the methods applied used 5 years. Stopping rules were used in 21 out of 30 (70.1%) of the appraisals for which the committee included waning, and waning assumptions were used more in oncology. The most common reason given for including TE waning assumptions was precedent from prior appraisals. CONCLUSIONS: Considerable heterogeneity existed in both the methods used and justifications given for TE waning assumptions. This variability poses a risk of inconsistent decision making. Reliance on past appraisals emphasizes the necessity to advocate for evidence-driven approaches and underscores the demand for guidance on suitable methods for incorporating assumptions.

Diminished neutralizing activity against the XBB1.5 strain in 55.9% of individuals post 6 months COVID-19 mRNA booster vaccination: insights from a pseudovirus assay on 1,353 participants in the Fukushima vaccination community survey, Japan.

This study investigates the neutralizing activity against the XBB1.5 variant and the ancestral strain in a population post-bivalent vaccination using a pseudo virus assay validated with authentic virus assay. While bivalent booster vaccination and past infections enhanced neutralization against the XBB 1.5 strain, individuals with comorbidities showed reduced responses. The study suggests the need for continuous vaccine updates to address emerging SARS-CoV-2 variants and highlights the importance of monitoring real-world immune responses.

Influence of waning immunity on vaccination decision-making: A multi-strain epidemic model with an evolutionary approach analyzing cost and efficacy.

In this research, we introduce a comprehensive epidemiological model that accounts for multiple strains of an infectious disease and two distinct vaccination options. Vaccination stands out as the most effective means to prevent and manage infectious diseases. However, when there are various vaccines available, each with its costs and effectiveness, the decision-making process for individuals becomes paramount. Furthermore, the factor of waning immunity following vaccination also plays a significant role in influencing these choices. To understand how individuals make decisions in the context of multiple strains and waning immunity, we employ a behavioral model, allowing an epidemiological model to be coupled with the dynamics of a decision-making process. Individuals base their choice of vaccination on factors such as the total number of infected individuals and the cost-effectiveness of the vaccine. Our findings indicate that as waning immunity increases, people tend to prioritize vaccines with higher costs and greater efficacy. Moreover, when more contagious strains are present, the equilibrium in vaccine adoption is reached more rapidly. Finally, we delve into the social dilemma inherent in our model by quantifying the social efficiency deficit (SED) under various parameter combinations.

Effectiveness of two and three doses of COVID-19 mRNA vaccines against infection, symptoms, and severity in the pre-omicron era: A time-dependent gradient.

BACKGROUND: Vaccines were developed and deployed to combat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This study aimed to characterize patterns in the protection provided by the BNT162b2 and mRNA-1273 mRNA vaccines against a spectrum of SARS-CoV-2 infection symptoms and severities. METHODS: A national, matched, test-negative, case-control study was conducted in Qatar between January 1 and December 18, 2021, utilizing a sample of 238,896 PCR-positive tests and 6,533,739 PCR-negative tests. Vaccine effectiveness was estimated against asymptomatic, symptomatic, severe coronavirus disease 2019 (COVID-19), critical COVID-19, and fatal COVID-19 infections. Data sources included Qatar's national databases for COVID-19 laboratory testing, vaccination, hospitalization, and death. RESULTS: Effectiveness of two-dose BNT162b2 vaccination was 75.6% (95% CI: 73.6-77.5) against asymptomatic infection and 76.5% (95% CI: 75.1-77.9) against symptomatic infection. Effectiveness against each of severe, critical, and fatal COVID-19 infections surpassed 90%. Immediately after the second dose, all categories-namely, asymptomatic, symptomatic, severe, critical, and fatal COVID-19-exhibited similarly high effectiveness. However, from 181 to 270 days post-second dose, effectiveness against asymptomatic and symptomatic infections declined to below 40%, while effectiveness against each of severe, critical, and fatal COVID-19 infections remained consistently high. However, estimates against fatal COVID-19 often had wide 95% confidence intervals. Analogous patterns were observed in three-dose BNT162b2 vaccination and two- and three-dose mRNA-1273 vaccination. Sensitivity analyses confirmed the results. CONCLUSION: A gradient in vaccine effectiveness exists and is linked to the symptoms and severity of infection, providing higher protection against more symptomatic and severe cases. This gradient intensifies over time as vaccine immunity wanes after the last vaccine dose. These patterns appear consistent irrespective of the vaccine type or whether the vaccination involves the primary series or a booster.

Reduced effectiveness of repeat influenza vaccination: distinguishing among within-season waning, recent clinical infection, and subclinical infection.

Studies have reported that prior-season influenza vaccination is associated with higher risk of clinical influenza infection among vaccinees. This effect might arise from incomplete consideration of within-season waning and recent infection. Using data from the US Flu Vaccine Effectiveness (VE) Network (2011-2012 to 2018-2019 seasons), we found that repeat vaccinees were vaccinated earlier in a season by one week. After accounting for waning VE, repeat vaccinees were still more likely to test positive for A(H3N2) (OR=1.11, 95%CI:1.02-1.21) but not for influenza B or A(H1N1). We found that clinical infection influenced individuals' decision to vaccinate in the following season while protecting against clinical infection of the same (sub)type. However, adjusting for recent clinical infections did not strongly influence the estimated effect of prior-season vaccination. In contrast, we found that adjusting for subclinical infection could theoretically attenuate this effect. Additional investigation is needed to determine the impact of subclinical infections on VE.

Seroconversion and Kinetics of Vibriocidal Antibodies during the First 90 Days of Re-Vaccination with Oral Cholera Vaccine in an Endemic Population.

Despite the successful introduction of oral cholera vaccines, Zambia continues to experience multiple, sporadic, and protracted cholera outbreaks in various parts of the country. While vaccines have been useful in staying the cholera outbreaks, the ideal window for re-vaccinating individuals resident in cholera hotspot areas remains unclear. Using a prospective cohort study design, 225 individuals were enrolled and re-vaccinated with two doses of Shanchol™, regardless of previous vaccination, and followed-up for 90 days. Bloods were collected at baseline before re-vaccination, at day 14 prior to second dosing, and subsequently on days 28, 60, and 90. Vibriocidal assay was performed on samples collected at all five time points. Our results showed that anti-LPS and vibriocidal antibody titers increased at day 14 after re-vaccination and decreased gradually at 28, 60, and 90 days across all the groups. Seroconversion rates were generally comparable in all treatment arms. We therefore conclude that vibriocidal antibody titers generated in response to re-vaccination still wane quickly, irrespective of previous vaccination status. However, despite the observed decline, the levels of vibriocidal antibodies remained elevated over baseline values across all groups, an important aspect for Zambia where there is no empirical evidence as to the ideal time for re-vaccination.

Durability of the Effectiveness of Heterologous COVID-19 Vaccine Regimens in Thailand: Retrospective Cohort Study Using National Registration Data.

BACKGROUND: The durability of heterologous COVID-19 vaccine effectiveness (VE) has been primarily studied in high-income countries, while evaluation of heterologous vaccine policies in low- and middle-income countries remains limited. OBJECTIVE: We aimed to evaluate the duration during which the VE of heterologous COVID-19 vaccine regimens in mitigating serious outcomes, specifically severe COVID-19 and death following hospitalization with COVID-19, remains over 50%. METHODS: We formed a dynamic cohort by linking records of Thai citizens aged ≥18 years from citizen vital, COVID-19 vaccine, and COVID-19 cases registry databases between May 2021 and July 2022. Encrypted citizen identification numbers were used to merge the data between the databases. This study focuses on 8 common heterologous vaccine sequences: CoronaVac/ChAdOx1, ChAdOx1/BNT162b2, CoronaVac/CoronaVac/ChAdOx1, CoronaVac/ChAdOx1/ChAdOx1, CoronaVac/ChAdOx1/BNT162b2, BBIBP-CorV/BBIBP-CorV/BNT162b2, ChAdOx1/ChAdOx1/BNT162b2, and ChAdOx1/ChAdOx1/mRNA-1273. Nonimmunized individuals were considered for comparisons. The cohort was stratified according to the vaccination status, age, sex, province location, month of vaccination, and outcome. Data analysis employed logistic regression to determine the VE, accounting for potential confounders and durability over time, with data observed over a follow-up period of 7 months. RESULTS: This study includes 52,580,841 individuals, with approximately 17,907,215 and 17,190,975 receiving 2- and 3-dose common heterologous vaccines (not mutually exclusive), respectively. The 2-dose heterologous vaccinations offered approximately 50% VE against severe COVID-19 and death following hospitalization with COVID-19 for 2 months; however, the protection significantly declined over time. The 3-dose heterologous vaccinations sustained over 50% VE against both outcomes for at least 8 months, as determined by logistic regression with durability time-interaction modeling. The vaccine sequence consisting of CoronaVac/CoronaVac/ChAdOx1 demonstrated >80% VE against both outcomes, with no evidence of VE waning. The final monthly measured VE of CoronaVac/CoronaVac/ChAdOx1 against severe COVID-19 and death following hospitalization at 7 months after the last dose was 82% (95% CI 80.3%-84%) and 86.3% (95% CI 83.6%-84%), respectively. CONCLUSIONS: In Thailand, within a 7-month observation period, the 2-dose regimens could not maintain a 50% VE against severe and fatal COVID-19 for over 2 months, but all of the 3-dose regimens did. The CoronaVac/CoronaVac/ChAdOx1 regimen showed the best protective effect against severe and fatal COVID-19. The estimated durability of 50% VE for at least 8 months across all 3-dose heterologous COVID-19 vaccine regimens supports the adoption of heterologous prime-boost vaccination strategies, with a primary series of inactivated virus vaccine and boosting with either a viral vector or an mRNA vaccine, to prevent similar pandemics in low- and middle-income countries.

Annual risk of hepatitis E virus infection and seroreversion: Insights from a serological cohort in Sitakunda, Bangladesh.

Hepatitis E virus (HEV) is a major cause of acute jaundice in South Asia. Gaps in our understanding of transmission are driven by non-specific symptoms and scarcity of diagnostics, impeding rational control strategies. In this context, serological data can provide important proxy measures of infection. We enrolled a population-representative serological cohort of 2,337 individuals in Sitakunda, Bangladesh. We estimated the annual risks of HEV infection and seroreversion both using serostatus changes between paired serum samples collected 9 months apart, and by fitting catalytic models to the age-stratified cross-sectional seroprevalence. At baseline, 15% (95 CI: 14-17%) of people were seropositive, with seroprevalence highest in the relatively urban south. During the study, 27 individuals seroreverted (annual seroreversion risk: 15%, 95 CI: 10-21%), and 38 seroconverted (annual infection risk: 3%, 95CI: 2-5%). Relying on cross-sectional seroprevalence data alone, and ignoring seroreversion, underestimated the annual infection risk five-fold (0.6%, 95 CrI: 0.5-0.6%). When we accounted for the observed seroreversion in a reversible catalytic model, infection risk was more consistent with measured seroincidence. Our results quantify HEV infection risk in Sitakunda and highlight the importance of accounting for seroreversion when estimating infection incidence from cross-sectional seroprevalence data.

Waning intra-season vaccine effectiveness against influenza A(H3N2) underlines the need for more durable protection.

BACKGROUND: The question of whether influenza vaccine effectiveness (VE) wanes over the winter season is still open and some contradictory findings have been reported. This study investigated the possible decline in protection provided by the available influenza vaccines. RESEARCH DESIGN AND METHODS: An individual-level pooled analysis of six test-negative case-control studies conducted in Italy between the 2018/2019 and 2022/2023 seasons was performed. Multivariable logistic regression analyses were performed to estimate weekly change in the odds of testing positive for influenza 14 days after vaccination. RESULTS: Of 6490 patients included, 1633 tested positive for influenza. Each week that had elapsed since vaccination was associated with an increase in the odds of testing positive for any influenza (4.9%; 95% CI: 2.0-8.0%) and for A(H3N2) (6.5%; 95% CI: 2.9-10.3%). This decline in VE was, however, significant only in children and older adults. A similar increase in the odds of testing positive was seen when the dataset was restricted to vaccinees only. Conversely, VE waning was less evident for A(H1N1)pdm09 or B strains. CONCLUSIONS: Significant waning of VE, especially against influenza A(H3N2), may be one of the factors associated with suboptimal end-of-season VE. Next-generation vaccines should provide more durable protection against A(H3N2).

Measuring waning protection from seasonal influenza vaccination during nine influenza seasons, Ontario, Canada, 2010/11 to 2018/19.

BackgroundWaning immunity from seasonal influenza vaccination can cause suboptimal protection during peak influenza activity. However, vaccine effectiveness studies assessing waning immunity using vaccinated and unvaccinated individuals are subject to biases.AimWe examined the association between time since vaccination and laboratory-confirmed influenza to assess the change in influenza vaccine protection over time.MethodsUsing linked laboratory and health administrative databases in Ontario, Canada, we identified community-dwelling individuals aged ≥ 6 months who received an influenza vaccine before being tested for influenza by RT-PCR during the 2010/11 to 2018/19 influenza seasons. We estimated the adjusted odds ratio (aOR) for laboratory-confirmed influenza by time since vaccination (categorised into intervals) and for every 28 days.ResultsThere were 53,065 individuals who were vaccinated before testing for influenza, with 10,264 (19%) influenza-positive cases. The odds of influenza increased from 1.05 (95% CI: 0.91-1.22) at 42-69 days after vaccination and peaked at 1.27 (95% CI: 1.04-1.55) at 126-153 days when compared with the reference interval (14-41 days). This corresponded to 1.09-times increased odds of influenza every 28 days (aOR = 1.09; 95% CI: 1.04-1.15). Individuals aged 18-64 years showed the greatest decline in protection against influenza A(H1N1) (aORper 28 days = 1.26; 95% CI: 0.97-1.64), whereas for individuals aged ≥ 65 years, it was against influenza A(H3N2) (aORper 28 days = 1.20; 95% CI: 1.08-1.33). We did not observe evidence of waning vaccine protection for individuals aged < 18 years.ConclusionsInfluenza vaccine protection wanes during an influenza season. Understanding the optimal timing of vaccination could ensure robust protection during seasonal influenza activity.

Probability of exposure to the wild measles virus in adult population - Estimation from seroepidemiology and historical data.

Vaccination against measles is one of the most effective public health interventions which has saved millions of lives and interrupted circulation of the natural virus in the population. However, it is widely accepted that the immunity after vaccination can wane, especially in those who have had no contact with the virus. This study aimed to classify the particular birth cohorts of adults with regard to their exposure to the wild measles virus in the population with a long history of mandatory vaccination. We introduced two methods. In the first, we estimated the probability of exposure to the wild virus through an analysis of antibody levels from the Immunologic Survey performed in the Slovak Republic in 2018, while the second was based on historical epidemiological data. Both methods resulted in similar estimations. Cohorts born in Slovakia before 1964 can be considered to be cohorts in which most people were exposed to the wild measles virus. Cohorts born after 1977 can be designated as cohorts that most likely did not come into the contact with the wild virus. Cohorts born between 1965 and 1976 are composed of a mixture, with a decreasing proportion of people exposed to the wild virus with increasing year of birth. The proposed methods can help identify potential immunity gaps in the adult population. They can be applied in other countries with high measles vaccination coverage to estimate the probability of exposure to the wild measles virus in particular birth cohorts.

Delay epidemic models determined by latency, infection, and immunity duration.

We propose new single and two-strain epidemic models represented by systems of delay differential equations and based on the number of newly exposed individuals. Transitions between exposed, infectious, recovered, and back to susceptible compartments are determined by the corresponding time delays. Existence and positiveness of solutions are proved. Reduction of delay differential equations to integral equations allows the analysis of stationary solutions and their stability. In the case of two strains, they compete with each other, and the strain with a larger individual basic reproduction number dominates the other one. However, if the basic reproduction number exceeds some critical values, stationary solution loses its stability resulting in periodic time oscillations. In this case, both strains are present and their dynamics is not completely determined by the basic reproduction numbers but also by other parameters. The results of the work are illustrated by comparison with data on seasonal influenza.