Abstract
Biased seroprevalence estimates can occur using serological assays optimized with validation sets unrepresentative of disease spectrum in the general population. Correct interpretation of ...serosurveys for severe acute respiratory syndrome coronavirus 2 requires quantifying variations in sensitivity with disease severity and over time.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infections in vaccinated individuals and reinfections in previously infected individuals have become increasingly common. ...Such infections highlight a broader need to understand the contribution of vaccination, including booster doses, and natural immunity to the infectiousness of individuals with SARS-CoV-2 infections, especially in high-risk populations with intense transmission, such as in prisons. Here we show that both vaccine-derived and naturally acquired immunity independently reduce the infectiousness of persons with Omicron variant SARS-CoV-2 infections in a prison setting. Analyzing SARS-CoV-2 surveillance data from December 2021 to May 2022 across 35 California state prisons with a predominately male population, we estimate that unvaccinated Omicron cases had a 36% (95% confidence interval (CI): 31-42%) risk of transmitting infection to close contacts, as compared to a 28% (25-31%) risk among vaccinated cases. In adjusted analyses, we estimated that any vaccination, prior infection alone and both vaccination and prior infection reduced an index case's risk of transmitting infection by 22% (6-36%), 23% (3-39%) and 40% (20-55%), respectively. Receipt of booster doses and more recent vaccination further reduced infectiousness among vaccinated cases. These findings suggest that, although vaccinated and/or previously infected individuals remain highly infectious upon SARS-CoV-2 infection in this prison setting, their infectiousness is reduced compared to individuals without any history of vaccination or infection. This study underscores benefit of vaccination to reduce, but not eliminate, transmission.
Serologic studies are crucial for clarifying dynamics of the coronavirus disease pandemic. Past work on serologic studies (e.g., during influenza pandemics) has made relevant contributions, but ...specific conditions of the current situation require adaptation. Although detection of antibodies to measure exposure, immunity, or both seems straightforward conceptually, numerous challenges exist in terms of sample collection, what the presence of antibodies actually means, and appropriate analysis and interpretation to account for test accuracy and sampling biases. Successful deployment of serologic studies depends on type and performance of serologic tests, population studied, use of adequate study designs, and appropriate analysis and interpretation of data. We highlight key questions that serologic studies can help answer at different times, review strengths and limitations of different assay types and study designs, and discuss methods for rapid sharing and analysis of serologic data to determine global transmission of severe acute respiratory syndrome coronavirus 2.
The first approved dengue vaccine has now been licensed in six countries. We propose that this live attenuated vaccine acts like a silent natural infection in priming or boosting host immunity. A ...transmission dynamic model incorporating this hypothesis fits recent clinical trial data well and predicts that vaccine effectiveness depends strongly on the age group vaccinated and local transmission intensity. Vaccination in low-transmission settings may increase the incidence of more severe "secondary-like" infection and, thus, the numbers hospitalized for dengue. In moderate transmission settings, we predict positive impacts overall but increased risks of hospitalization with dengue disease for individuals who are vaccinated when séronégative. However, in high-transmission settings, vaccination benefits both the whole population and séronégative recipients. Our analysis can help inform policy-makers evaluating this and other candidate dengue vaccines.
Population based serological surveys are the gold-standard to quantify dengue (DENV) transmission. The purpose of this study was to estimate the age-specific seroprevalence and the force of infection ...of DENV in an endemic area of Colombia. Between July and October 2014, we conducted a household based cross-sectional survey among 1.037 individuals aged 2 to 40 years living in 40 randomly selected locations in urban Piedecuesta, Santander, Colombia. In addition, we also enrolled 246 indviduals living in rural "veredas". Participants were asked to answer a questionnaire that included demographic, socioeconomic and environmental questions and to provide a 5 ml blood sample. Sera were tested using the IgG indirect ELISA (Panbio) kit to determine past DENV infection. The overall DENV seroprevalence was 70% (95% CI = 67%-71%), but was significantly higher in urban (81%, 95% CI = 78%-83%) as compared to rural (21%, 95% CI = 17%-27%) locations. Age was a major predictor of seropositivity, consistent with endemic circulation of the virus. Using catalytic models we estimated that on average, 12% (95%CI = 11%-13%) of susceptible individuals living in the city are infected by DENV each year. Beyond age, the only predictor of seropositivity in urban locations was prior history of dengue diagnosed by a physician (aPR 1.15, 95% CI = 0.98-1.35). Among participants living in rural settings, those that reported traveling outside of their vereda were more likely to be seropositive (aPR 3.60, 95%CI = 1.54-8.42) as well as those who were born outside of Santander department (aPR = 2.77, 95%CI = 1.20-6.37). These results are consistent with long term endemic circulation of DENV in Piedecuesta, with large heterogeneities between urban and rural areas located just a few kilometers apart. Design of DENV control interventions, including vaccination, will need to consider this fine scale spatial heterogeneity.
Large Phase III trials across Asia and Latin America have recently demonstrated the efficacy of a recombinant, live-attenuated dengue vaccine (Dengvaxia) over the first 25 mo following vaccination. ...Subsequent data collected in the longer-term follow-up phase, however, have raised concerns about a potential increase in hospitalization risk of subsequent dengue infections, in particular among young, dengue-naïve vaccinees. We here report predictions from eight independent modelling groups on the long-term safety, public health impact, and cost-effectiveness of routine vaccination with Dengvaxia in a range of transmission settings, as characterised by seroprevalence levels among 9-y-olds (SP9). These predictions were conducted for the World Health Organization to inform their recommendations on optimal use of this vaccine.
The models adopted, with small variations, a parsimonious vaccine mode of action that was able to reproduce quantitative features of the observed trial data. The adopted mode of action assumed that vaccination, similarly to natural infection, induces transient, heterologous protection and, further, establishes a long-lasting immunogenic memory, which determines disease severity of subsequent infections. The default vaccination policy considered was routine vaccination of 9-y-old children in a three-dose schedule at 80% coverage. The outcomes examined were the impact of vaccination on infections, symptomatic dengue, hospitalised dengue, deaths, and cost-effectiveness over a 30-y postvaccination period. Case definitions were chosen in accordance with the Phase III trials. All models predicted that in settings with moderate to high dengue endemicity (SP9 ≥ 50%), the default vaccination policy would reduce the burden of dengue disease for the population by 6%-25% (all simulations: -3%-34%) and in high-transmission settings (SP9 ≥ 70%) by 13%-25% (all simulations: 10%- 34%). These endemicity levels are representative of the participating sites in both Phase III trials. In contrast, in settings with low transmission intensity (SP9 ≤ 30%), the models predicted that vaccination could lead to a substantial increase in hospitalisation because of dengue. Modelling reduced vaccine coverage or the addition of catch-up campaigns showed that the impact of vaccination scaled approximately linearly with the number of people vaccinated. In assessing the optimal age of vaccination, we found that targeting older children could increase the net benefit of vaccination in settings with moderate transmission intensity (SP9 = 50%). Overall, vaccination was predicted to be potentially cost-effective in most endemic settings if priced competitively. The results are based on the assumption that the vaccine acts similarly to natural infection. This assumption is consistent with the available trial results but cannot be directly validated in the absence of additional data. Furthermore, uncertainties remain regarding the level of protection provided against disease versus infection and the rate at which vaccine-induced protection declines.
Dengvaxia has the potential to reduce the burden of dengue disease in areas of moderate to high dengue endemicity. However, the potential risks of vaccination in areas with limited exposure to dengue as well as the local costs and benefits of routine vaccination are important considerations for the inclusion of Dengvaxia into existing immunisation programmes. These results were important inputs into WHO global policy for use of this licensed dengue vaccine.
Routine viral testing strategies for SARS-CoV-2 infection might facilitate safe airline travel during the COVID-19 pandemic and mitigate global spread of the virus. However, the effectiveness of ...these test-and-travel strategies to reduce passenger risk of SARS-CoV-2 infection and population-level transmission remains unknown.
In this simulation study, we developed a microsimulation of SARS-CoV-2 transmission in a cohort of 100 000 US domestic airline travellers using publicly available data on COVID-19 clinical cases and published natural history parameters to assign individuals one of five health states of susceptible to infection, latent period, early infection, late infection, or recovered. We estimated a per-day risk of infection with SARS-CoV-2 corresponding to a daily incidence of 150 infections per 100 000 people. We assessed five testing strategies: (1) anterior nasal PCR test within 3 days of departure, (2) PCR within 3 days of departure and 5 days after arrival, (3) rapid antigen test on the day of travel (assuming 90% of the sensitivity of PCR during active infection), (4) rapid antigen test on the day of travel and PCR test 5 days after arrival, and (5) PCR test 5 days after arrival. Strategies 2 and 4 included a 5-day quarantine after arrival. The travel period was defined as 3 days before travel to 2 weeks after travel. Under each scenario, individuals who tested positive before travel were not permitted to travel. The primary study outcome was cumulative number of infectious days in the cohort over the travel period without isolation or quarantine (population-level transmission risk), and the key secondary outcome was the number of infectious people detected on the day of travel (passenger risk of infection).
We estimated that in a cohort of 100 000 airline travellers, in a scenario with no testing or screening, there would be 8357 (95% uncertainty interval 6144–12831) infectious days with 649 (505–950) actively infectious passengers on the day of travel. The pre-travel PCR test reduced the number of infectious days from 8357 to 5401 (3917–8677), a reduction of 36% (29–41) compared with the base case, and identified 569 (88% 76–92) of 649 actively infectious travellers on the day of flight; the addition of post-travel quarantine and PCR reduced the number of infectious days to 1474 (1087–2342), a reduction of 82% (80–84) compared with the base case. The rapid antigen test on the day of travel reduced the number of infectious days to 5674 (4126–9081), a reduction of 32% (26–38) compared with the base case, and identified 560 (86% 83–89) actively infectious travellers; the addition of post-travel quarantine and PCR reduced the number of infectious days to 2518 (1935–3821), a reduction of 70% (67–72) compared with the base case. The post-travel PCR alone reduced the number of infectious days to 4851 (3714–7679), a reduction of 42% (35–49) compared with the base case.
Routine asymptomatic testing for SARS-CoV-2 before travel can be an effective strategy to reduce passenger risk of infection during travel, although abbreviated quarantine with post-travel testing is probably needed to reduce population-level transmission due to importation of infection when travelling from a high to low incidence setting.
University of California, San Francisco.
Many public health responses and modeled scenarios for COVID-19 outbreaks caused by SARS-CoV-2 assume that infection results in an immune response that protects individuals from future infections or ...illness for some amount of time. The presence or absence of protective immunity due to infection or vaccination (when available) will affect future transmission and illness severity. Here, we review the scientific literature on antibody immunity to coronaviruses, including SARS-CoV-2 as well as the related SARS-CoV, MERS-CoV and endemic human coronaviruses (HCoVs). We reviewed 2,452 abstracts and identified 491 manuscripts relevant to 5 areas of focus: 1) antibody kinetics, 2) correlates of protection, 3) immunopathogenesis, 4) antigenic diversity and cross-reactivity, and 5) population seroprevalence. While further studies of SARS-CoV-2 are necessary to determine immune responses, evidence from other coronaviruses can provide clues and guide future research.
A key public health question during any disease outbreak when limited vaccine is available is who should be prioritized for early vaccination. Most vaccine prioritization analyses only consider ...variation in risk of infection and death by a single risk factor, such as age. We provide a more granular approach with stratification by demographics, risk factors, and location. We use this approach to compare the impact of different COVID-19 vaccine prioritization strategies on COVID-19 cases, deaths and disability-adjusted life years (DALYs) over the first 6 months of vaccine rollout, using California as a case example. We estimate the proportion of cases, deaths and DALYs averted relative to no vaccination for strategies prioritizing vaccination by a single risk factor and by multiple risk factors (e.g. age, location). When targeting by a single risk factor, we find that age-based targeting averts the most deaths (62% for 5 million individuals vaccinated) and DALYs (38%) and targeting essential workers averts the least deaths (31%) and DALYs (24%) over the first 6 months of rollout. However, targeting by two or more risk factors simultaneously averts up to 40% more DALYs. Our findings highlight the potential value of multiple-risk-factor targeting of vaccination against COVID-19 and other infectious diseases, but must be balanced with feasibility for policy.
Because current evidence suggests that the vaccine confers good protection against symptomatic and severe disease in individuals seropositive to dengue virus, WHO has recommended screening potential ...vaccine recipients to minimise harm to seronegative individuals while maximising benefits to seropositive people.3 As noted by Annelies Wilder-Smith and colleagues, many challenges to the implementation of this recommendation exist.4 Screening tests would need to be highly sensitive and specific, and deliverable at the point of care. Focusing on the positive predictive value (PPV) makes more sense, as this value directly quantifies the probability that a person who tests positive is truly seropositive, or the probability that they have been misclassified (1 – PPV). ...rather than uniformly fixing the desired sensitivity and specificity of the test, it might be more reasonable to decide what an acceptable level of misclassification is, and to find the minimum sensitivity and specificity for different transmission settings that would achieve this level of misclassification or lower. Developing a test that ensures acceptable levels of misclassification might be more feasible for endemic regions with high transmission, and it is in these settings that models predict the vaccine could have the largest benefits with regard to protecting individuals from symptomatic and severe disease.5 Developing screening assays that are specific enough for settings with moderate or low transmission will be more challenging and might not be possible, particularly where individuals might have been exposed to other flaviviruses (either by vaccination or natural infection) such as yellow fever virus, Japanese encephalitis virus, or Zika virus, all of which are known to serologically cross-react with dengue virus in most available immunological assays.
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