Now showing 1 - 10 of 18
  • Publication
    Incubation period of COVID-19: a rapid systematic review and meta-analysis of observational research
    Objectives: The aim of this study was to conduct a rapid systematic review and meta-analysis of estimates of the incubation period of COVID-19. Design: Rapid systematic review and meta-analysis of observational research. Setting: International studies on incubation period of COVID-19. Participants: Searches were carried out in PubMed, Google Scholar, Embase, Cochrane Library as well as the preprint servers MedRxiv and BioRxiv. Studies were selected for meta-analysis if they reported either the parameters and CIs of the distributions fit to the data, or sufficient information to facilitate calculation of those values. After initial eligibility screening, 24 studies were selected for initial review, nine of these were shortlisted for meta-analysis. Final estimates are from meta-analysis of eight studies. Primary outcome measures: Parameters of a lognormal distribution of incubation periods. Results: The incubation period distribution may be modelled with a lognormal distribution with pooled mu and sigma parameters (95% CIs) of 1.63 (95% CI 1.51 to 1.75) and 0.50 (95% CI 0.46 to 0.55), respectively. The corresponding mean (95% CIs) was 5.8 (95% CI 5.0 to 6.7) days. It should be noted that uncertainty increases towards the tail of the distribution: the pooled parameter estimates (95% CIs) resulted in a median incubation period of 5.1 (95% CI 4.5 to 5.8) days, whereas the 95th percentile was 11.7 (95% CI 9.7 to 14.2) days. Conclusions: The choice of which parameter values are adopted will depend on how the information is used, the associated risks and the perceived consequences of decisions to be taken. These recommendations will need to be revisited once further relevant information becomes available. Accordingly, we present an R Shiny app that facilitates updating these estimates as new data become available.
      248Scopus© Citations 235
  • Publication
    COVID-19 epidemiological parameters summary document
    In response to the coronavirus (COVID-19) outbreak, the Irish Epidemiological Modelling Advisory Group (IEMAG) for COVID-19 was established to assist the Irish National Public Health Emergency Team (NPHET) in their decision-making during the pandemic. A subcommittee from IEMAG (the epidemiological parameters team) was tasked with researching the various parameters, leading to the development of a series of synthesis documents relevant to the parameterisation of a COVID-19 transmission model for Ireland. These parameters include: • R0/R • Latent period & relative importance of pre-symptomatic period • Incubation period • Generation time & serial interval • Proportion of infected who are asymptomatic, by age • Length of infectious period in asymptomatic people and in symptomatic people who do not isolate • Time from onset of symptoms to diagnosis/test results and to hospitalisation • Length of hospital stay and admission to ICUs • Relative infectiousness of asymptomatic versus symptomatic infected people. The current document presents an up-to-date summary of these synthesis documents. A further synthesis document on age-related susceptibility and age-related infectiousness is in preparation.
      109
  • Publication
    Epidemiological analyses to support national control of SARS-CoV-2 in Ireland
    (University College Dublin. School of Public Health, Physiotherapy and Sports Science, 2022) ;
    0000-0002-4984-4031
    Pathogen emergence has been increasing in recent decades. In December 2019, an outbreak of atypical pneumonia emerged in Wuhan, central China. The cause of the disease, was subsequently identified as a novel coronavirus (SARS-CoV-2) and the disease named COVID-19. Over a short period of time SARS-CoV-2 rapidly spread throughout mainland China and surrounding countries in the western pacific before cases appeared in Europe in February of 2020. The first case in Ireland was documented in Ireland on the 29th of February 2020. In response, a series of epidemiological analyses were conducted to support decision making in the national control of the disease. The objective of this thesis was to provide regions-specific estimates of region-specific epidemiological parameters of interest, to aid in the accurate modelling of the disease in the country. The ultimate goal was to improve models so that more accurate information could be provided to decision makers. Chapter one proposed the use of the number of close contacts of infected cases over time as a metric for monitoring behaviour of infected contacts. The study found that the distribution of contacts per case was overdispersed, with a small proportion of cases reporting very large numbers of contacts. The study also provided an evidence basis for mathematical age-cohort compartmental models, by providing data on the social contacts of the Irish population under different levels of restriction. Chapter two estimated the serial interval of SARS-CoV-2 in Ireland using contact tracing data. The median serial interval was 4.0 days which was lower than estimates previously used for the statistical approximation of the serial interval in Ireland. Furthermore, the study also suggested that up to two thirds of transmission events were likely to have occurred prior to the onset of symptoms in the primary case. Finally, chapter three evaluated the potential use of Rapid Antigen Diagnostic Tests in screening individuals attending mass gatherings. The baseline risk of infection in the tested population is of key importance when interpreting the results of any imperfect diagnostic tests. This study provided a mechanism for estimating the baseline risk, as well as the uncertainty around that risk, using incidence data. The studies presented in this thesis demonstrate that secondary analyses of contact tracing data can yield meaningful and useful pieces of information that may be used to more accurately reflect transmission in the population of interest. However, it is also worth pointing out that certain opportunities were underutilized in the collection and analysis of contact tracing data. Given the apparent acceleration of pathogen emergence, evidenced in particular by the temporal proximity of repeated coronavirus outbreaks in the past 20 years, it is vital that Ireland take steps to develop infrastructure to deal with the current pandemic as well as the threat of future endemic diseases. Similar to work in other countries, this thesis demonstrates the strength of a OneHealth approach to the management of emerging infectious diseases.
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  • Publication
    Potential Application of SARS-CoV-2 Rapid Antigen Diagnostic Tests for the Detection of Infectious Individuals Attending Mass Gatherings – A Simulation Study
    Rapid Antigen Diagnostic Tests (RADTs) for the detection of SARS-CoV-2 offer advantages in that they are cheaper and faster than currently used PCR tests but have reduced sensitivity and specificity. One potential application of RADTs is to facilitate gatherings of individuals, through testing of attendees at the point of, or immediately prior to entry at a venue. Understanding the baseline risk in the tested population is of particular importance when evaluating the utility of applying diagnostic tests for screening purposes. We used incidence data from January and from July-August 2021, periods of relatively high and low levels of infection, to estimate the prevalence of infectious individuals in the community at particular time points and simulated mass gatherings by sampling froma series of age cohorts. Nine different illustrative scenarios were simulated, small (n = 100), medium (n = 1,000) and large (n = 10,000) gatherings each with 3 possible age constructs: mostly younger, mostly older or a gathering with equal numbers from each age cohort. For each scenario, we estimated the prevalence of infectious attendees, then simulated the likely number of positive and negative test results, the proportion of cases detected and the corresponding positive and negative predictive values, and the cost per case identified. Our findings suggest that for each reported case on a given day, there are likely to be 13.8 additional infectious individuals also present in the community. Prevalence ranged from 0.26% for “mostly older” events in July-August, to 2.6% for “mostly younger” events in January. For small events (100 attendees) the expected number of infectious attendees ranged from <1 across all age constructs of attendees in July-August, to 2.6 for “mostly younger” events in January. For large events (10,000 attendees) the expected number of infectious attendees ranged from 27 (95% confidence intervals 12 to 45) for mostly older events in July-August, to 267 (95% confidence intervals 134 to 436) infectious attendees for mostly younger attendees in January. Given rapid changes in SARS-CoV-2 incidence over time, we developed an RShiny app to allow users to run updated simulations for specific events.
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  • Publication
    The Herd-Level Sensitivity of Abattoir Surveillance for Bovine Tuberculosis: Simulating the Effects of Current and Potentially Modified Meat Inspection Procedures in Irish Cattle
    The European Food Safety Authority (EFSA) has published a series of opinions to assess the impact of changing from the current meat inspection procedures (CMI) to visual-only inspection (VOI) procedures. Concern has been raised that changes from CMI to VOI would adversely affect the effectiveness of surveillance for bovine tuberculosis (bTB) in EU member states, both for countries with and without official status of bTB freedom (OTF and non-OTF countries, respectively). This study was conducted to estimate the impact of a change from CMI to VOI in abattoirs on herd-level detection sensitivity in Ireland, a non-OTF country. Using national Irish data, we identified all herds that sold at least one animal to slaughter during 2010-12 whilst unrestricted for bTB. For each of these herds, we calculated the number of cattle sent to slaughter whilst unrestricted, the number of factory lesion tests (FLT) that had been performed, and estimated the apparent within-herd prevalence (APwh). A FLT is a whole-herd test conducted in a herd following the confirmation of bTB in an animal at slaughter. We considered five different inspection scenarios, each based on meat inspection and bacteriology in series, including current meat inspection (CMI) and four visual-only inspection scenarios (VOI2, VOI3, VOI4, VOI5) with reducing inspection sensitivities. Separately for each inspection scenario, a simulation model was used to estimate the herd-level detection sensitivity and the number of bTB-herds (that is, herds that sent at least one animal detected with M. bovis to slaughter when unrestricted during 2010-12) that would and would not be detected. The simulated mean herd-level detection sensitivity estimates were 0.24 for CMI, and 0.16, 0.12, 0.10 and 0.08 for VOI2-5, assuming a 2-, 3-, 4-and 5-fold decrease, respectively, in the animal-level detection sensitivity of VOI relative to that of CMI. The estimated number of non-detected bTB-herds is substantial with CMI, and increases in the series of VOI scenarios with decreasing herd-level detection sensitivity. If VOI were introduced without alternative surveillance means to compensate for the decrease in animal-level inspection sensitivity, such changes might jeopardise bTB surveillance, control and eradication programmes in cattle herds of non-OTF countries, including Ireland.
      230Scopus© Citations 12
  • Publication
    Relative infectiousness of asymptomatic SARS-CoV-2 infected persons compared with symptomatic individuals: a rapid scoping review
    Objectives The aim of this study was to determine the relative infectiousness of asymptomatic SARS-CoV-2 infected persons compared with symptomatic individuals based on a scoping review of available literature. Design Rapid scoping review of peer-reviewed literature from 1 January to 5 December 2020 using the LitCovid database and the Cochrane library. Setting International studies on the infectiousness of individuals infected with SARS-CoV-2. Participants Studies were selected for inclusion if they defined asymptomatics as a separate cohort distinct from presymptomatics and if they provided a quantitative measure of the infectiousness of asymptomatics relative to symptomatics. Primary outcome measures PCR result (PCR studies), the rate of infection (mathematical modelling studies) and secondary attack rate (contact tracing studies) - in each case from asymptomatic in comparison with symptomatic individuals. Results There are only a limited number of published studies that report estimates of relative infectiousness of asymptomatic compared with symptomatic individuals. 12 studies were included after the screening process. Significant differences exist in the definition of infectiousness. PCR studies in general show no difference in shedding levels between symptomatic and asymptomatic individuals; however, the number of study subjects is generally limited. Two modelling studies estimate relative infectiousness to be 0.43 and 0.57, but both of these were more reflective of the infectiousness of undocumented rather than asymptomatic cases. The results from contact tracing studies include estimates of relative infectiousness of 0, but with insufficient evidence to conclude that it is significantly different from 1. Conclusions There is considerable heterogeneity in estimates of relative infectiousness highlighting the need for further investigation of this important parameter. It is not possible to provide any conclusive estimate of relative infectiousness, as the estimates from the reviewed studies varied between 0 and 1.
      151Scopus© Citations 19
  • Publication
    Presymptomatic transmission of SARS-CoV-2 infection: a secondary analysis using published data
    Objective To estimate the proportion of presymptomatic transmission of SARS-CoV-2 infection that can occur, and the timing of transmission relative to symptom onset.Setting/design Secondary analysis of international published data.Data sources Meta-analysis of COVID-19 incubation period and a rapid review of serial interval and generation time, which are published separately.Participants Data from China, the Islamic Republic of Iran, Italy, Republic of Korea, Singapore and Vietnam from December 2019 to May 2020.Methods Simulations were generated of incubation period and of serial interval or generation time. From these, transmission times relative to symptom onset, and the proportion of presymptomatic transmission, were estimated.Outcome measures Transmission time of SARS-CoV-2 relative to symptom onset and proportion of presymptomatic transmission.Results Based on 18 serial interval/generation time estimates from 15 papers, mean transmission time relative to symptom onset ranged from −2.6 (95% CI −3.0 to –2.1) days before infector symptom onset to 1.4 (95% CI 1.0 to 1.8) days after symptom onset. The proportion of presymptomatic transmission ranged from 45.9% (95% CI 42.9% to 49.0%) to 69.1% (95% CI 66.2% to 71.9%).Conclusions There is substantial potential for presymptomatic transmission of SARS-CoV-2 across a range of different contexts. This highlights the need for rapid case detection, contact tracing and quarantine. The transmission patterns that we report reflect the combination of biological infectiousness and transmission opportunities which vary according to context.
      173Scopus© Citations 18
  • Publication
    Numbers of close contacts of individuals infected with SARS-CoV-2 and their association with government intervention strategies
    Background: Contact tracing is conducted with the primary purpose of interrupting transmission from individuals who are likely to be infectious to others. Secondary analyses of data on the numbers of close contacts of confirmed cases could also: provide an early signal of increases in contact patterns that might precede larger than expected case numbers; evaluate the impact of government interventions on the number of contacts of confirmed cases; or provide data information on contact rates between age cohorts for the purpose of epidemiological modelling. We analysed data from 140,204 close contacts of 39,861 cases in Ireland from 1st May to 1st December 2020. Results: Negative binomial regression models highlighted greater numbers of contacts within specific population demographics, after correcting for temporal associations. Separate segmented regression models of the number of cases over time and the average number of contacts per case indicated that a breakpoint indicating a rapid decrease in the number of contacts per case in October 2020 preceded a breakpoint indicating a reduction in the number of cases by 11 days. Conclusions: We found that the number of contacts per infected case was overdispersed, the mean varied considerable over time and was temporally associated with government interventions. Analysis of the reported number of contacts per individual in contact tracing data may be a useful early indicator of changes in behaviour in response to, or indeed despite, government restrictions. This study provides useful information for triangulating assumptions regarding the contact mixing rates between different age cohorts for epidemiological modelling.
      130Scopus© Citations 2
  • Publication
    Estimation of the serial interval and proportion of pre-symptomatic transmission events of COVID-19 in Ireland using contact tracing data
    The serial interval is the period of time between the onset of symptoms in an infector and an infectee and is an important parameter which can impact on the estimation of the reproduction number. Whilst several parameters influencing infection transmission are expected to be consistent across populations, the serial interval can vary across and within populations over time. Therefore, local estimates are preferable for use in epidemiological models developed at a regional level. We used data collected as part of the national contact tracing process in Ireland to estimate the serial interval of SARS-CoV-2 infection in the Irish population, and to estimate the proportion of transmission events that occurred prior to the onset of symptoms. Results After data cleaning, the final dataset consisted of 471 infected close contacts from 471 primary cases. The median serial interval was 4 days, mean serial interval was 4.0 (95% confidence intervals 3.7, 4.3) days, whilst the 25th and 75th percentiles were 2 and 6 days respectively. We found that intervals were lower when the primary or secondary case were in the older age cohort (greater than 64 years). Simulating from an incubation period distribution from international literature, we estimated that 67% of transmission events had greater than 50% probability of occurring prior to the onset of symptoms in the infector. Conclusions Whilst our analysis was based on a large sample size, data were collected for the primary purpose of interrupting transmission chains. Similar to other studies estimating the serial interval, our analysis is restricted to transmission pairs where the infector is known with some degree of certainty. Such pairs may represent more intense contacts with infected individuals than might occur in the overall population. It is therefore possible that our analysis is biased towards shorter serial intervals than the overall population.
      136Scopus© Citations 3
  • Publication
    Evaluation of national surveillance methods for detection of Irish dairy herds infected with Mycobacterium avium ssp. paratuberculosis
    The aim of this study was to evaluate the utility and cost-effectiveness of a range of national surveillance methods for paratuberculosis in Irish dairy herds. We simulated alternative surveillance strategies applied to dairy cattle herds for the detection of Mycobacterium avium ssp. paratuberculosis (MAP)-infected herds (case-detection) or for estimation of confidence of herd freedom from infection (assurance testing). Strategies simulated included whole-herd milk or serum serology, serology on cull cows at slaughter, bulk milk tank serology, environmental testing, and pooled fecal testing. None of the strategies evaluated were ideal for widespread national case-detection surveillance. Herd testing with milk or serum ELISA or pooled fecal testing were the most effective methods currently available for detection of MAP-infected herds, with median herd sensitivity >60% and 100% herd specificity, although they are relatively expensive for widespread use. Environmental sampling shows promise as an alternative, with median herd sensitivity of 69%, but is also expensive unless samples can be pooled and requires further validation under Irish conditions. Bulk tank milk testing is the lowest cost option and may be useful for detecting high-prevalence herds but had median herd sensitivity <10% and positive predictive value of 85%. Cull cow sampling strategies were also lower cost but had median herd sensitivity <40% and herd positive predictive values of <50%, resulting in an increased number of test-positive herds, each of which requires follow-up herd testing to clarify status. Possible false-positive herd testing results associated with prior tuberculosis testing also presented logistical issues for both cull cow and bulk milk testing. Whole-herd milk or serum ELISA testing are currently the preferred testing strategies to estimate confidence of herd freedom from MAP in dairy herds due to the good technical performance and moderate cost of these strategies for individual herd testing. Cull cow serology and bulk tank milk sampling provide only minimal assurance value, with confidence of herd freedom increasing only minimally above the prior estimate. Different testing strategies should be considered when deciding on cost-effective approaches for case-detection compared with those used for building confidence of herd freedom (assurance testing) as part of a national program.
      129Scopus© Citations 21