Publications
255 results found
Dighe A, Cattarino L, Cuomo-Dannenburg G, et al., 2020, Report 25: Response to COVID-19 in South Korea and implications for lifting stringent interventions, 25
While South Korea experienced a sharp growth in COVID-19 cases early in the global pandemic, it has since rapidly reduced rates of infection and now maintains low numbers of daily new cases. Despite using less stringent “lockdown” measures than other affected countries, strong social distancing measures have been advised in high incidence areas and a 38% national decrease in movement occurred voluntarily between February 24th - March 1st. Suspected and confirmed cases were isolated quickly even during the rapid expansion of the epidemic and identification of the Shincheonji cluster. South Korea swiftly scaled up testing capacity and was able to maintain case-based interventions throughout. However, individual case-based contact tracing, not associated with a specific cluster, was a relatively minor aspect of their control program, with cluster investigations accounting for a far higher proportion of cases: the underlying epidemic was driven by a series of linked clusters, with 48% of all cases in the Shincheonji cluster and 20% in other clusters. Case-based contacts currently account for only 11% of total cases. The high volume of testing and low number of deaths suggests that South Korea experienced a small epidemic of infections relative to other countries. Therefore, caution is needed in attempting to duplicate the South Korean response in settings with larger more generalized epidemics. Finding, testing and isolating cases that are linked to clusters may be more difficult in such settings.
Jeffrey B, Walters C, Ainslie K, et al., 2020, Report 24: Mobility data from mobile phones suggests that initial compliance with COVID-19 social distancing interventions was high and geographically consistent across the UK, 24
Since early March 2020, the COVID-19 epidemic across the United Kingdom has led to a range of socialdistancing policies, which have resulted in reduced mobility across different regions. Crowd level dataon mobile phone usage can be used as a proxy for actual population mobility patterns and provide away of quantifying the impact of social distancing measures on changes in mobility. Here, we use twomobile phone-based datasets (anonymised and aggregated crowd level data from O2 and from theFacebook app on mobile phones) to assess changes in average mobility, both overall and broken downinto high and low population density areas, and changes in the distribution of journey lengths. Weshow that there was a substantial overall reduction in mobility with the most rapid decline on the 24thMarch 2020, the day after the Prime Minister’s announcement of an enforced lockdown. Thereduction in mobility was highly synchronized across the UK. Although mobility has remained low since26th March 2020, we detect a gradual increase since that time. We also show that the two differentdatasets produce similar trends, albeit with some location-specific differences. We see slightly largerreductions in average mobility in high-density areas than in low-density areas, with greater variationin mobility in the high-density areas: some high-density areas eliminated almost all mobility. We areonly able to observe populations living in locations where sufficient number of people use Facebookor a device connected to the relevant provider’s network such that no individual is identifiable. Theseanalyses form a baseline with which to monitor changes in behaviour in the UK as social distancing iseased.
Mellan T, Hoeltgebaum H, Mishra S, et al., 2020, Report 21: Estimating COVID-19 cases and reproduction number in Brazil
Brazil is an epicentre for COVID-19 in Latin America. In this report we describe the Brazilian epidemicusing three epidemiological measures: the number of infections, the number of deaths and the reproduction number. Our modelling framework requires sufficient death data to estimate trends, and wetherefore limit our analysis to 16 states that have experienced a total of more than fifty deaths. Thedistribution of deaths among states is highly heterogeneous, with 5 states—São Paulo, Rio de Janeiro,Ceará, Pernambuco and Amazonas—accounting for 81% of deaths reported to date. In these states, weestimate that the percentage of people that have been infected with SARS-CoV-2 ranges from 3.3% (95%CI: 2.8%-3.7%) in São Paulo to 10.6% (95% CI: 8.8%-12.1%) in Amazonas. The reproduction number (ameasure of transmission intensity) at the start of the epidemic meant that an infected individual wouldinfect three or four others on average. Following non-pharmaceutical interventions such as school closures and decreases in population mobility, we show that the reproduction number has dropped substantially in each state. However, for all 16 states we study, we estimate with high confidence that thereproduction number remains above 1. A reproduction number above 1 means that the epidemic isnot yet controlled and will continue to grow. These trends are in stark contrast to other major COVID19 epidemics in Europe and Asia where enforced lockdowns have successfully driven the reproductionnumber below 1. While the Brazilian epidemic is still relatively nascent on a national scale, our resultssuggest that further action is needed to limit spread and prevent health system overload.
Hay JA, Minter A, Ainslie KEC, et al., 2020, An open source tool to infer epidemiological and immunological dynamics from serological data: serosolver, PLOS COMPUTATIONAL BIOLOGY, Vol: 16, ISSN: 1553-734X
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- Citations: 8
Ainslie KEC, Walters CE, Fu H, et al., 2020, Evidence of initial success for China exiting COVID-19 social distancing policy after achieving containment [version 1; peer review: 2 approved], Wellcome Open Res, Vol: 5, ISSN: 2398-502X
Background: The COVID-19 epidemic was declared a Global Pandemic by WHO on 11 March 2020. By 24 March 2020, over 440,000 cases and almost 20,000 deaths had been reported worldwide. In response to the fast-growing epidemic, which began in the Chinese city of Wuhan, Hubei, China imposed strict social distancing in Wuhan on 23 January 2020 followed closely by similar measures in other provinces. These interventions have impacted economic productivity in China, and the ability of the Chinese economy to resume without restarting the epidemic was not clear. Methods: Using daily reported cases from mainland China and Hong Kong SAR, we estimated transmissibility over time and compared it to daily within-city movement, as a proxy for economic activity. Results: Initially, within-city movement and transmission were very strongly correlated in the five mainland provinces most affected by the epidemic and Beijing. However, that correlation decreased rapidly after the initial sharp fall in transmissibility. In general, towards the end of the study period, the correlation was no longer apparent, despite substantial increases in within-city movement. A similar analysis for Hong Kong shows that intermediate levels of local activity were maintained while avoiding a large outbreak. At the very end of the study period, when China began to experience the re-introduction of a small number of cases from Europe and the United States, there is an apparent up-tick in transmission. Conclusions: Although these results do not preclude future substantial increases in incidence, they suggest that after very intense social distancing (which resulted in containment), China successfully exited its lockdown to some degree. Elsewhere, movement data are being used as proxies for economic activity to assess the impact of interventions. The results presented here illustrate how the eventual decorrelation between transmission and movement is likely a key feature of successful COVID-19 exit strategies.
Arinaminpathy N, Riley S, Barclay W, et al., 2020, Population implications of the deployment of novel universal vaccines against epidemic and pandemic influenza, Journal of the Royal Society Interface, ISSN: 1742-5662
Biggerstaff M, Dahlgren FS, Fitzner J, et al., 2020, Coordinating the real-time use of global influenza activity data for better public health planning, Influenza and Other Respiratory Viruses, Vol: 14, Pages: 105-110, ISSN: 1750-2640
Health planners from global to local levels must anticipate year-to-year andweek-to-week variation in seasonal influenza activity when planning for andresponding to epidemics to mitigate their impact. To help with this, countries routinelycollect incidence of mild and severe respiratory illness and virologic data oncirculating subtypes and use this data for situational awareness, burden of diseaseestimates and severity assessments. Advanced analytics and modelling areincreasingly used to aid planning and response activities by describing key featuresof influenza activity for a given location and generating forecasts that can betranslated to useful actions such as enhanced risk communications, and informingclinical supply chains. Here, we describe the formation of the Influenza IncidenceAnalytics Group (IIAG),a coordinated global effort to apply advanced analytics andmodelling to public influenza data, both epidemiological and virologic, in real-time andthus provide additional insights to countries who provide routine surveillance data toWHO. Our objectives are to systematically increase the value of data to healthplanners by applying advanced analytics and forecasting and for results to beimmediately reproducible and deployable using an open repository of data and code.We expect the resources we develop and the associated community to provide anattractive option for the open analysis of key epidemiological data during seasonalepidemics and the early stages of an influenza pandemic.
Riley S, Atchison C, Ashby D, et al., 2020, REal-time Assessment of Community Transmission (REACT) of SARS-CoV-2 virus: Study protocol [version 1; peer review: 1 approved, 1 approved with reservations], Wellcome Open Research, Vol: 5, Pages: 1-17
Background: England, UK has one of the highest rates of confirmed COVID-19 mortality globally. Until recently, testing for the SARS-CoV-2 virus focused mainly on healthcare and care home settings. As such, there is far less understanding of community transmission. Protocol: The REal-time Assessment of Community Transmission (REACT) programme is a major programme of home testing for COVID-19 to track progress of the infection in the community. REACT-1 involves cross-sectional surveys of viral detection (virological swab for RT-PCR) tests in repeated samples of 100,000 to 150,000 randomly selected individuals across England. This examines how widely the virus has spread and how many people are currently infected. The age range is 5 years and above. Individuals are sampled from the England NHS patient list. REACT-2 is a series of five sub-studies towards establishing the seroprevalence of antibodies to SARS-CoV-2 in England as an indicator of historical infection. The main study (study 5) uses the same design and sampling approach as REACT-1 using a self-administered lateral flow immunoassay (LFIA) test for IgG antibodies in repeated samples of 100,000 to 200,000 adults aged 18 years and above. To inform study 5, studies 1-4 evaluate performance characteristics of SARS-CoV-2 LFIAs (study 1) and different aspects of feasibility, usability and application of LFIAs for home-based testing in different populations (studies 2-4). Ethics and dissemination: The study has ethical approval. Results are reported using STROBE guidelines and disseminated through reports to public health bodies, presentations at scientific meetings and open access publications. Conclusions: This study provides robust estimates of the prevalence of both virus (RT-PCR, REACT-1) and seroprevalence (antibody, REACT-2) in the general population in England. We also explore acceptability and usability of LFIAs for self-administered testing for SARS-CoV-2 antibody in a home-based setting, not done before at
Ward H, Cooke G, Atchison C, et al., 2020, Declining prevalence of antibody positivity to SARS-CoV-2: a community study of 365,000 adults
Background The prevalence and persistence of antibodies following a peak SARS-CoV-2 infection provides insights into its spread in the community, the likelihood of reinfection and potential for some level of population immunity.Methods Prevalence of antibody positivity in England, UK (REACT2) with three cross-sectional surveys between late June and September 2020. 365104 adults used a self-administered lateral flow immunoassay (LFIA) test for IgG. A laboratory comparison of LFIA results to neutralization activity in panel of sera was performed.Results There were 17,576 positive tests over the three rounds. Antibody prevalence, adjusted for test characteristics and weighted to the adult population of England, declined from 6.0% [5.8, 6.1], to 4.8% [4.7, 5.0] and 4.4% [4.3, 4.5], a fall of 26.5% [-29.0, −23.8] over the three months of the study. There was a decline between rounds 1 and 3 in all age groups, with the highest prevalence of a positive result and smallest overall decline in positivity in the youngest age group (18-24 years: −14.9% [-21.6, −8.1]), and lowest prevalence and largest decline in the oldest group (75+ years: −39.0% [-50.8, −27.2]); there was no change in antibody positivity between rounds 1 and 3 in healthcare workers (+3.45% [-5.7, +12.7]).The decline from rounds 1 to 3 was largest in those who did not report a history of COVID-19, (−64.0% [-75.6, −52.3]), compared to −22.3% ([-27.0, −17.7]) in those with SARS-CoV-2 infection confirmed on PCR.Discussion These findings provide evidence of variable waning in antibody positivity over time such that, at the start of the second wave of infection in England, only 4.4% of adults had detectable IgG antibodies using an LFIA. Antibody positivity was greater in those who reported a positive PCR and lower in older people and those with asymptomatic infection. These data suggest the possibility of decreasing population immunity and increasing risk of rei
Bhatia S, Imai N, Cuomo-Dannenburg G, et al., 2020, Estimating the number of undetected COVID-19 cases among travellers from mainland China., Wellcome open research, Vol: 5, Pages: 143-143, ISSN: 2398-502X
Background: As of August 2021, every region of the world has been affected by the COVID-19 pandemic, with more than 196,000,000 cases worldwide.Methods: We analysed COVID-19 cases among travellers from mainland China to different regions and countries, comparing the region- and country-specific rates of detected and confirmed cases per flight volume to estimate the relative sensitivity of surveillance in different regions and countries.Results: Although travel restrictions from Wuhan City and other cities across China may have reduced the absolute number of travellers to and from China, we estimated that up to 70% (95% CI: 54% - 80%) of imported cases could remain undetected relative to the sensitivity of surveillance in Singapore. The percentage of undetected imported cases rises to 75% (95% CI 66% - 82%) when comparing to the surveillance sensitivity in multiple countries.Conclusions: Our analysis shows that a large number of COVID-19 cases remain undetected across the world. These undetected cases potentially resulted in multiple chains of human-to-human transmission outside mainland China.
Jeffrey B, Walters CE, Ainslie KEC, et al., 2020, Anonymised and aggregated crowd level mobility data from mobile phones suggests that initial compliance with COVID-19 social distancing interventions was high and geographically consistent across the UK., Wellcome Open Res, Vol: 5, ISSN: 2398-502X
Background: Since early March 2020, the COVID-19 epidemic across the United Kingdom has led to a range of social distancing policies, which have resulted in reduced mobility across different regions. Crowd level data on mobile phone usage can be used as a proxy for actual population mobility patterns and provide a way of quantifying the impact of social distancing measures on changes in mobility. Methods: Here, we use two mobile phone-based datasets (anonymised and aggregated crowd level data from O2 and from the Facebook app on mobile phones) to assess changes in average mobility, both overall and broken down into high and low population density areas, and changes in the distribution of journey lengths. Results: We show that there was a substantial overall reduction in mobility, with the most rapid decline on the 24th March 2020, the day after the Prime Minister's announcement of an enforced lockdown. The reduction in mobility was highly synchronized across the UK. Although mobility has remained low since 26th March 2020, we detect a gradual increase since that time. We also show that the two different datasets produce similar trends, albeit with some location-specific differences. We see slightly larger reductions in average mobility in high-density areas than in low-density areas, with greater variation in mobility in the high-density areas: some high-density areas eliminated almost all mobility. Conclusions: These analyses form a baseline from which to observe changes in behaviour in the UK as social distancing is eased and inform policy towards the future control of SARS-CoV-2 in the UK.
Riley S, Atchison C, Ashby D, et al., 2020, REal-time Assessment of Community Transmission (REACT) of SARS-CoV-2 virus: Study protocol., Wellcome Open Res, Vol: 5, ISSN: 2398-502X
Background: England, UK has one of the highest rates of confirmed COVID-19 mortality globally. Until recently, testing for the SARS-CoV-2 virus focused mainly on healthcare and care home settings. As such, there is far less understanding of community transmission. Protocol: The REal-time Assessment of Community Transmission (REACT) programme is a major programme of home testing for COVID-19 to track progress of the infection in the community. REACT-1 involves cross-sectional surveys of viral detection (virological swab for RT-PCR) tests in repeated samples of 100,000 to 150,000 randomly selected individuals across England. This examines how widely the virus has spread and how many people are currently infected. The age range is 5 years and above. Individuals are sampled from the England NHS patient list. REACT-2 is a series of five sub-studies towards establishing the seroprevalence of antibodies to SARS-CoV-2 in England as an indicator of historical infection. The main study (study 5) uses the same design and sampling approach as REACT-1 using a self-administered lateral flow immunoassay (LFIA) test for IgG antibodies in repeated samples of 100,000 to 200,000 adults aged 18 years and above. To inform study 5, studies 1-4 evaluate performance characteristics of SARS-CoV-2 LFIAs (study 1) and different aspects of feasibility, usability and application of LFIAs for home-based testing in different populations (studies 2-4). Ethics and dissemination: The study has ethical approval. Results are reported using STROBE guidelines and disseminated through reports to public health bodies, presentations at scientific meetings and open access publications. Conclusions: This study provides robust estimates of the prevalence of both virus (RT-PCR, REACT-1) and seroprevalence (antibody, REACT-2) in the general population in England. We also explore acceptability and usability of LFIAs for self-administered testing for SARS-CoV-2 antibody in a home-based setting, not done before at
Pepin KM, Hopken MW, Shriner SA, et al., 2019, Improving risk assessment of the emergence of novel influenza A viruses by incorporating environmental surveillance, PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, Vol: 374, ISSN: 0962-8436
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- Citations: 12
Hay JA, Laurie K, White M, et al., 2019, Characterising antibody kinetics from multiple influenza infection and vaccination events in ferrets, PLOS COMPUTATIONAL BIOLOGY, Vol: 15
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- Citations: 6
Rivers C, Chretien J-P, Riley S, et al., 2019, Using "outbreak science" to strengthen the use of models during epidemics, NATURE COMMUNICATIONS, Vol: 10, ISSN: 2041-1723
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- Citations: 64
Ben-Nun M, Riley P, Turtle J, et al., 2019, Forecasting national and regional influenza-like illness for the USA, PLOS COMPUTATIONAL BIOLOGY, Vol: 15, ISSN: 1553-734X
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- Citations: 8
Suwannahitatorn P, Webster J, Riley S, et al., 2019, Uncooked fish consumption among those at risk of Opisthorchis viverrini infection in central Thailand, PLoS ONE, Vol: 14, Pages: 1-13, ISSN: 1932-6203
In contrast to northern and northeastern Thailand, central Thailand was believed not to be endemic for Opisthorchis viverrini (OV). Fieldwork conducted in a rural area of central Thailand revealed that the prevalence and incidence were relatively high compared with regional average data. We hypothesized that the behavioural-psycho-social background of the study population might play an important role in the high burden of the infection. As a result, a qualitative study was conducted to highlight potential social determinants of the infection dynamics to gain greater understanding of the risk behaviours and their contexts. A qualitative study using focus group discussion and in-depth interviews was conducted in Na-ngam Village, Chachoengsao Province from 2012–14. Framework analysis was used to explore associations between infection and thematic content. Social influence showed a strong impact on infection dynamics of OV infection. Our results revealed that Koi pla (chopped raw fish salad) remains a popular dish in the community, as the dish itself represents northeastern culture. The cultural norm had been transferred from ancestors to their descendants. Some elders complained that discontinuing the consumption of Koi pla went against old traditions with respect to cultural norms and socialization. In contrast, modern education teaches about hygiene including OV infection risks, and accordingly teenagers and young adults were reported to modify their lifestyles including their eating habits. Children are a potential key to pass knowledge to their parents and school-based education programs can serve as a practical hub for knowledge dissemination. However, health education alone might not lead to behavioural change in other age groups. Therefore, more efforts are needed to support the transformation.
Kwok KO, Tang A, Wei VWI, et al., 2019, Epidemic models of contact tracing: systematic review of transmission studies of severe acute respiratory syndrome and Middle East respiratory syndrome, Computational and Structural Biotechnology Journal, Vol: 17, Pages: 186-194, ISSN: 2001-0370
The emergence and reemergence of coronavirus epidemics sparked renewed concerns from global epidemiology researchers and public health administrators. Mathematical models that represented how contact tracing and follow-up may control Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) transmissions were developed for evaluating different infection control interventions, estimating likely number of infections as well as facilitating understanding of their likely epidemiology. We reviewed mathematical models for contact tracing and follow-up control measures of SARS and MERS transmission. Model characteristics, epidemiological parameters and intervention parameters used in the mathematical models from seven studies were summarized. A major concern identified in future epidemics is whether public health administrators can collect all the required data for building epidemiological models in a short period of time during the early phase of an outbreak. Also, currently available models do not explicitly model constrained resources. We urge for closed-loop communication between public health administrators and modelling researchers to come up with guidelines to delineate the collection of the required data in the midst of an outbreak and the inclusion of additional logistical details in future similar models.
McGowan CJ, Biggerstaff M, Johansson M, et al., 2019, Collaborative efforts to forecast seasonal influenza in the United States, 2015-2016., Sci Rep, Vol: 9
Since 2013, the Centers for Disease Control and Prevention (CDC) has hosted an annual influenza season forecasting challenge. The 2015-2016 challenge consisted of weekly probabilistic forecasts of multiple targets, including fourteen models submitted by eleven teams. Forecast skill was evaluated using a modified logarithmic score. We averaged submitted forecasts into a mean ensemble model and compared them against predictions based on historical trends. Forecast skill was highest for seasonal peak intensity and short-term forecasts, while forecast skill for timing of season onset and peak week was generally low. Higher forecast skill was associated with team participation in previous influenza forecasting challenges and utilization of ensemble forecasting techniques. The mean ensemble consistently performed well and outperformed historical trend predictions. CDC and contributing teams will continue to advance influenza forecasting and work to improve the accuracy and reliability of forecasts to facilitate increased incorporation into public health response efforts.
Haw DJ, Cummings DAT, Lessler J, et al., 2019, Differential mobility and local variation in infection attack rate, PLOS COMPUTATIONAL BIOLOGY, Vol: 15
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- Citations: 7
Hay JA, Nouvellet P, Donnelly CA, et al., 2018, Potential inconsistencies in Zika surveillance data and our understanding of risk during pregnancy, PLoS Neglected Tropical Diseases, Vol: 12, ISSN: 1935-2727
BackgroundA significant increase in microcephaly incidence was reported in Northeast Brazil at the end of 2015, which has since been attributed to an epidemic of Zika virus (ZIKV) infections earlier that year. Further incidence of congenital Zika syndrome (CZS) was expected following waves of ZIKV infection throughout Latin America; however, only modest increases in microcephaly and CZS incidence have since been observed. The quantitative relationship between ZIKV infection, gestational age and congenital outcome remains poorly understood.Methodology/Principle findingsWe characterised the gestational-age-varying risk of microcephaly given ZIKV infection using publicly available incidence data from multiple locations in Brazil and Colombia. We found that the relative timings and shapes of ZIKV infection and microcephaly incidence curves suggested different gestational risk profiles for different locations, varying in both the duration and magnitude of gestational risk. Data from Northeast Brazil suggested a narrow window of risk during the first trimester, whereas data from Colombia suggested persistent risk throughout pregnancy. We then used the model to estimate which combination of behavioural and reporting changes would have been sufficient to explain the absence of a second microcephaly incidence wave in Bahia, Brazil; a population for which we had two years of data. We found that a 18.9-fold increase in ZIKV infection reporting rate was consistent with observed patterns.ConclusionsOur study illustrates how surveillance data may be used in principle to answer key questions in the absence of directed epidemiological studies. However, in this case, we suggest that currently available surveillance data are insufficient to accurately estimate the gestational-age-varying risk of microcephaly from ZIKV infection. The methods used here may be of use in future outbreaks and may help to inform improved surveillance and interpretation in countries yet to experience an out
Wong JWH, Ip M, Tang A, et al., 2018, Prevalence and risk factors of community-associated methicillin-resistant Staphylococcus aureus carriage in Asia-Pacific region from 2000 to 2016: a systematic review and meta-analysis, Clinical Epidemiology, Vol: 10, Pages: 1489-1501, ISSN: 1179-1349
Objective: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is an emerging global public health threat. In response to a highlighted strategic priority of the World Health Organization Global Action Plan on Antimicrobial Resistance, to “strengthen the knowledge and evidence base through surveillance and research”, we synthesized published articles to estimate CA-MRSA carriage prevalence in the Asia-Pacific region.Methods: A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO CRD:42017067399). We searched MEDLINE, EMBASE, and PubMed for articles published from 1 January 2000 to 19 May 2017, which reported CA-MRSA carriage (defined as either colonization or infection) in Asia-Pacific region from 2000 to 2016. Studies were stratified according to settings (community or hospital where CA-MRSA was isolated) and study populations (general public or subpopulations with specified characteristics). Ranges of CA-MRSA carriage prevalence were reported for study groups.Results: In total, 152 studies were identified. Large diversity was observed among studies in most study groups. In community-level studies, the CA-MRSA carriage prevalence among the general public ranged from 0% to 23.5%, whereas that ranged from 0.7% to 10.4% in hospital settings. From community-level studies, countries with the highest prevalence were India (16.5%–23.5%), followed by Vietnam (7.9%) and Taiwan (3.5%–3.8%). Children aged ≤6 (range: 0.5%–40.3%) and household members of CA-MRSA carriers (range: 13.0%–26.4%) are subgroups without specific health conditions but with much higher CA-MRSA carriage when compared to the general population.Conclusion: Our CA-MRSA prevalence estimates serve as the baseline for future national and international surveillance. The ranges of prevalence and characteristics associated with CA-MRSA carriage can inform health authoritie
Hay JA, Laurie K, White M, et al., 2018, Characterising antibody kinetics from multiple influenza infection and vaccination events in ferrets
<jats:title>Abstract</jats:title><jats:p>The strength and breadth of an individual’s antibody repertoire are important predictors of their response to influenza infection or vaccination. Although progress has been made in understanding qualitatively how repeated exposures shape the antibody mediated immune response, quantitative understanding remains limited. We developed a set of mathematical models describing short-term antibody kinetics following influenza infection or vaccination and fit them to haemagglutination inhibition (HI) titres from 5 groups of ferrets which were exposed to different combinations of trivalent inactivated influenza vaccine (TIV with or without adjuvant), A/H3N2 priming inoculation and post-vaccination A/H1N1 inoculation. We fit models with various immunological mechanisms that have been empirically observed but are yet to be included in mathematical models of antibody landscapes, including titre ceiling effects, antigenic seniority and exposure-type specific cross reactivity. Based on the parameter estimates of the best supported models, we describe a number of key immunological features. We found quantifiable differences in the degree of homologous and cross-reactive antibody boosting elicited by different exposure types. Infection and adjuvanted vaccination generally resulted in strong, broadly reactive responses whereas unadjuvanted vaccination resulted in a weak, narrow response. We found that the order of exposure mattered: priming with A/H3N2 improved subsequent vaccine response, and the second dose of adjuvanted vaccination resulted in substantially greater antibody boosting than the first. Either antigenic seniority or a titre ceiling effect were included in the two best fitting models, suggesting that a mechanism describing diminishing antibody boosting with repeated exposures improved the predictive power of the model. Although there was considerable uncertainty in our estimates of antibody waning paramet
Kucharski AJ, Lessler J, Cummings DAT, et al., 2018, Timescales of influenza A/H3N2 antibody dynamics, PLoS Biology, Vol: 16, ISSN: 1544-9173
Human immunity influences the evolution and impact of influenza strains. Because individuals are infected with multiple influenza strains during their lifetime, and each virus can generate a cross-reactive antibody response, it is challenging to quantify the processes thatshape observed immune responses or to reliably detect recent infection from serologicalsamples. Using a Bayesian model of antibody dynamics at multiple timescales, we explaincomplex cross-reactive antibody landscapes by inferring participants’ histories of infectionwith serological data from cross-sectional and longitudinal studies of influenza A/H3N2 insouthern China and Vietnam. We find that individual-level influenza antibody profiles canbe explained by a short-lived, broadly cross-reactive response that decays within a yearto leave a smaller long-term response acting against a narrower range of strains. We alsodemonstrate that accounting for dynamic immune responses alongside infection history canprovide a more accurate alternative to traditional definitions of seroconversion for the estimation of infection attack rates. Our work provides a general model for quantifying aspectsof influenza immunity acting at multiple timescales based on contemporary serological dataand suggests a two-armed immune response to influenza infection consistent with competitive dynamics between B cell populations. This approach to analysing multiple timescalesfor antigenic responses could also be applied to other multistrain pathogens such as dengueand related flaviviruses.
Wong JWH, Ip M, Tang A, et al., 2018, Prevalence and risk factors of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) carriage in Asia-Pacific region from 2000 to 2016: A systematic review and meta-analysis, Clinical Epidemiology, Vol: 10, Pages: 1489-1501, ISSN: 1179-1349
Objective: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is an emerging global public health threat. In response to a highlighted strategic priority of the World Health Organization Global Action Plan on Antimicrobial Resistance, to “strengthen the knowledge and evidence base through surveillance and research”, we synthesized published articles to estimate CA-MRSA carriage prevalence in the Asia-Pacific region.Methods: A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO CRD:42017067399). We searched MEDLINE, EMBASE, and PubMed for articles published from 1 January 2000 to 19 May 2017, which reported CA-MRSA carriage (defined as either colonization or infection) in Asia-Pacific region from 2000 to 2016. Studies were stratified according to settings (community or hospital where CA-MRSA was isolated) and study populations (general public or subpopulations with specified characteristics). Ranges of CA-MRSA carriage prevalence were reported for study groups.Results: In total, 152 studies were identified. Large diversity was observed among studies in most study groups. In community-level studies, the CA-MRSA carriage prevalence among the general public ranged from 0% to 23.5%, whereas that ranged from 0.7% to 10.4% in hospital settings. From community-level studies, countries with the highest prevalence were India (16.5%–23.5%), followed by Vietnam (7.9%) and Taiwan (3.5%–3.8%). Children aged ≤6 (range: 0.5%–40.3%) and household members of CA-MRSA carriers (range: 13.0%–26.4%) are subgroups without specific health conditions but with much higher CA-MRSA carriage when compared to the general population.Conclusion: Our CA-MRSA prevalence estimates serve as the baseline for future national and international surveillance. The ranges of prevalence and characteristics associated with CA-MRSA carriage can inform health authoritie
Cremin Í, Watson O, Heffernan A, et al., 2018, An infectious way to teach students about outbreaks, Epidemics, Vol: 23, Pages: 42-48, ISSN: 1755-4365
The study of infectious disease outbreaks is required to train today’s epidemiologists. A typical way to introduce and explain key epidemiological concepts is through the analysis of a historical outbreak. There are, however, few training options that explicitly utilise real-time simulated stochastic outbreaks where the participants themselves comprise the dataset they subsequently analyse. In this paper, we present a teaching exercise in which an infectious disease outbreak is simulated over a five-day period and subsequently analysed. We iteratively developed the teaching exercise to offer additional insight into analysing an outbreak. An R package for visualisation, analysis and simulation of the outbreak data was developed to accompany the practical to reinforce learning outcomes. Computer simulations of the outbreak revealed deviations from observed dynamics, highlighting how simplifying assumptions conventionally made in mathematical models often differ from reality. Here we provide a pedagogical tool for others to use and adapt in their own settings.
Wei VWI, Wong JYT, Perera RAPM, et al., 2018, Incidence of influenza A(H3N2) virus infections in Hong Kong in a longitudinal sero-epidemiological study, 2009-2015, PLOS ONE, Vol: 13, ISSN: 1932-6203
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- Citations: 8
Kwok KO, Read JM, Tang A, et al., 2018, A systematic review of transmission dynamic studies of methicillin-resistant Staphylococcus aureus in non-hospital residential facilities, BMC Infectious Diseases, Vol: 18, ISSN: 1471-2334
BackgroundNon-hospital residential facilities are important reservoirs for MRSA transmission. However, conclusions and public health implications drawn from the many mathematical models depicting nosocomial MRSA transmission may not be applicable to these settings. Therefore, we reviewed the MRSA transmission dynamics studies in defined non-hospital residential facilities to: (1) provide an overview of basic epidemiology which has been addressed; (2) identify future research direction; and (3) improve future model implementation.MethodsA review was conducted by searching related keywords in PUBMED without time restriction as well as internet searches via Google search engine. We included only articles describing the epidemiological transmission pathways of MRSA/community-associated MRSA within and between defined non-hospital residential settings.ResultsAmong the 10 included articles, nursing homes (NHs) and correctional facilities (CFs) were two settings considered most frequently. Importation of colonized residents was a plausible reason for MRSA outbreaks in NHs, where MRSA was endemic without strict infection control interventions. The importance of NHs over hospitals in increasing nosocomial MRSA prevalence was highlighted. Suggested interventions in NHs included: appropriate staffing level, screening and decolonizing, and hand hygiene. On the other hand, the small population amongst inmates in CFs has no effect on MRSA community transmission. Included models ranged from system-level compartmental models to agent-based models. There was no consensus over the course of disease progression in these models, which were mainly featured with NH residents /CF inmates/ hospital patients as transmission pathways. Some parameters used by these models were outdated or unfit.ConclusionsImportance of NHs has been highlighted from these current studies addressing scattered aspects of MRSA epidemiology. However, the wide variety of non-hospital residential settings suggest th
Kwok KO, Cowling B, Wei V, et al., 2018, Temporal variation of human encounters and the number of locations in which they occur: a longitudinal study of Hong Kong residents, Journal of the Royal Society Interface, Vol: 15, ISSN: 1742-5662
Patterns of social contact between individuals are important for the transmission of many pathogens and shaping patterns of immunity at the population scale. To refine our understanding of how human social behaviour may change over time, we conducted a longitudinal study of Hong Kong residents. We recorded the social contact patterns for 1450 individuals, up to four times each between May 2012 and September 2013. We found individuals made contact with an average of 12.5 people within 2.9 geographical locations, and spent an average estimated total duration of 9.1 h in contact with others during a day. Distributions of the number of contacts and locations in which contacts were made were not significantly different between study waves. Encounters were assortative by age, and the age mixing pattern was broadly consistent across study waves. Fitting regression models, we examined the association of contact rates (number of contacts, total duration of contact, number of locations) with covariates and calculated the inter- and intra-participant variation in contact rates. Participant age was significantly associated with the number of contacts made, the total duration of contact and the number of locations in which contact occurred, with children and parental-age adults having the highest rates of contact. The number of contacts and contact duration increased with the number of contact locations. Intra-individual variation in contact rate was consistently greater than inter-individual variation. Despite substantial individual-level variation, remarkable consistency was observed in contact mixing at the population scale. This suggests that aggregate measures of mixing behaviour derived from cross-sectional information may be appropriate for population-scale modelling purposes, and that if more detailed models of social interactions are required for improved public health modelling, further studies are needed to understand the social processes driving intra-individual vari
Pinsent A, Pepin KM, Zhu H, et al., 2017, The persistence of multiple strains of avian influenza in live bird markets., Proceedings of the Royal Society B: Biological Sciences, Vol: 284, ISSN: 1471-2954
Multiple subtypes of avian influenza (AI) and novel reassortants are frequently isolated from live bird markets (LBMs). However, our understanding of the drivers of persistence of multiple AI subtypes is limited. We propose a stochastic model of AI transmission within an LBM that incorporates market size, turnover rate and the balance of direct versus environmental transmissibility. We investigate the relationship between these factors and the critical community size (CCS) for the persistence of single and multiple AI strains within an LBM. We fit different models of seeding from farms to two-strain surveillance data collected from Shantou, China. For a single strain and plausible estimates for continuous turnover rates and transmissibility, the CCS was approximately 11 800 birds, only a 4.2% increase in this estimate was needed to ensure persistence of the co-infecting strains (two strains in a single host). Precise values of CCS estimates were sensitive to changes in market turnover rate and duration of the latent period. Assuming a gradual daily sell rate of birds the estimated CCS was higher than when an instantaneous selling rate was assumed. We were able to reproduce prevalence dynamics similar to observations from a single market in China with infection seeded every 5-15 days, and a maximum non-seeding duration of 80 days. Our findings suggest that persistence of co-infections is more likely to be owing to sequential infection of single strains rather than ongoing transmission of both strains concurrently. In any given system for a fixed set of ecological and epidemiological conditions, there is an LBM size below which the risk of sustained co-circulation is low and which may suggest a clear policy opportunity to reduce the frequency of influenza co-infection in poultry.
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