Suchergebnisse

BACKGROUND: Infectious disease outbreaks present unique challenges to study designs for vaccine evaluation. Test-negative design (TND) studies have previously been used to estimate vaccine effectiveness and have been proposed for Ebola virus disease (EVD) vaccines. However, there are key differences in how cases and controls are recruited during outbreaks and pandemics of novel pathogens, whcih have implications for the reliability of effectiveness estimates using this design. METHODS: We use a modelling approach to quantify TND bias for a prophylactic vaccine under varying study and epidemiological scenarios. Our model accounts for heterogeneity in vaccine distribution and for two potential routes to testing and recruitment into the study: self-reporting and contact-tracing. We derive conventional and hybrid TND estimators for this model and suggest ways to translate public health response data into the parameters of the model. RESULTS: Using a conventional TND study, our model finds biases in vaccine effectiveness estimates. Bias arises due to differential recruitment from self-reporting and contact-tracing, and due to clustering of vaccination. We estimate the degree of bias when recruitment route is not available, and propose a study design to eliminate the bias if recruitment route is recorded. CONCLUSIONS: Hybrid TND studies can resolve the design bias with conventional TND studies applied to outbreak and pandemic response testing data, if those efforts collect individuals' routes to testing. Without route to testing, other epidemiological data will be required to estimate the magnitude of potential bias in a conventional TND study. Since these studies may need to be conducted retrospectively, public health responses should obtain these data, and generic protocols for outbreak and pandemic response studies should emphasize the need to record routes to testing.

Health care workers (HCW) are at high risk of Ebola virus disease (EVD) infection during epidemics and may contribute to onward transmission, and therefore HCW-targeted prophylactic vaccination strategies are being considered as interventions. To assess the feasibility of preventive HCW vaccination, we conducted a pilot survey on staff turnover and vaccine acceptance amongst 305 HCW in Freetown and Kambia districts of Sierra Leone. Multivariable logistic regression demonstrated which demographic and behavioural factors were associated with acceptance of a hypothetical new vaccine. We quantified the duration of employment of HCW, and used multivariable gamma regression to detect associations with duration of employment in current or any health care position. Finally, we simulated populations of HCW, to determine the likely future immunisation coverage amongst HCW based on our estimates of vaccine acceptance and employment duration. Most HCW we surveyed had a positive opinion of EVD vaccination (76.3%). We found that being a volunteer HCW (vs being on the government payroll) was associated with increased vaccine acceptance. We found that HCW have stable employment, with a mean duration of employment in the health sector of 10.9 years (median 8.0 years). Older age and being on the government payroll (vs volunteer HCW) were associated with a longer duration of employment in the health sector. Assuming a single vaccine campaign, with 76.3% vaccine acceptance, 100% vaccine efficacy and no waning of vaccine-induced protection, immunisation coverage was sustained over 50% until 6 years after a vaccination campaign. If vaccine-induced immunity wanes at 10% per year, then the immunisation coverage among HCW would fall below 50% after 3 years. Vaccinating HCW against EVD could be feasible as employment appeared stable and vaccine acceptance high. However, even with high vaccine efficacy and long-lasting immunity, repeated campaigns or vaccination at employment start may be necessary to maintain high coverage.

Funder: World Health Organization ; Background: Approval for the use of COVID-19 vaccines has been granted in a number of countries but there are concerns that vaccine uptake may be low amongst certain groups. Methods: This study used a mixed methods approach based on online survey and an embedded quantitative/qualitative design to explore perceptions and attitudes that were associated with intention to either accept or refuse offers of vaccination in different demographic groups during the early stages of the UK's mass COVID-19 vaccination programme (December 2020). Analysis used multivariate logistic regression, structural text modeling and anthropological assessments. Results: Of 4,535 respondents, 85% (n = 3,859) were willing to have a COVID-19 vaccine. The rapidity of vaccine development and uncertainties about safety were common reasons for COVID-19 vaccine hesitancy. There was no evidence for the widespread influence of mis-information, although broader vaccine hesitancy was associated with intentions to refuse COVID-19 vaccines (OR 20.60, 95% CI 14.20-30.30, p < 0.001). Low levels of trust in the decision-making (OR 1.63, 95% CI 1.08, 2.48, p = 0.021) and truthfulness (OR 8.76, 95% CI 4.15-19.90, p < 0.001) of the UK government were independently associated with higher odds of refusing COVID-19 vaccines. Compared to political centrists, conservatives and liberals were, respectively, more (OR 2.05, 95%CI 1.51-2.80, p < 0.001) and less (OR 0.30, 95% CI 0.22-0.41, p < 0.001) likely to refuse offered vaccines. Those who were willing to be vaccinated cited both personal and public protection as reasons, with some alluding to having a sense of collective responsibility. Conclusion: Dominant narratives of COVID-19 vaccine hesitancy are misconceived as primarily being driven by misinformation. Key indicators of UK vaccine acceptance include prior behaviors, transparency of the scientific process of vaccine development, mistrust in science and leadership and individual political views. Vaccine programmes should leverage the sense of altruism, citizenship and collective responsibility that motivated many participants to get vaccinated.

Background: Approval for the use of COVID-19 vaccines has been granted in a number of countries but there are concerns that vaccine uptake may be low amongst certain groups.Methods: This study used a mixed methods approach based on online survey and an embedded quantitative/qualitative design to explore perceptions and attitudes that were associated with intention to either accept or refuse offers of vaccination in different demographic groups during the early stages of the UK's mass COVID-19 vaccination programme (December 2020). Analysis used multivariate logistic regression, structural text modeling and anthropological assessments.Results: Of 4,535 respondents, 85% (n = 3,859) were willing to have a COVID-19 vaccine. The rapidity of vaccine development and uncertainties about safety were common reasons for COVID-19 vaccine hesitancy. There was no evidence for the widespread influence of mis-information, although broader vaccine hesitancy was associated with intentions to refuse COVID-19 vaccines (OR 20.60, 95% CI 14.20–30.30, p p = 0.021) and truthfulness (OR 8.76, 95% CI 4.15–19.90, p p p Conclusion: Dominant narratives of COVID-19 vaccine hesitancy are misconceived as primarily being driven by misinformation. Key indicators of UK vaccine acceptance include prior behaviors, transparency of the scientific process of vaccine development, mistrust in science and leadership and individual political views. Vaccine programmes should leverage the sense of altruism, citizenship and collective responsibility that motivated many participants to get vaccinated.

Background: Approval for the use of COVID-19 vaccines has been granted in a number of countries but there are concerns that vaccine uptake may be low amongst certain groups. Methods: This study used a mixed methods approach based on online survey and an embedded quantitative/qualitative design to explore perceptions and attitudes that were associated with intention to either accept or refuse offers of vaccination in different demographic groups during the early stages of the UK's mass COVID-19 vaccination programme (December 2020). Analysis used multivariate logistic regression, structural text modeling and anthropological assessments. Results: Of 4,535 respondents, 85% (n = 3,859) were willing to have a COVID-19 vaccine. The rapidity of vaccine development and uncertainties about safety were common reasons for COVID-19 vaccine hesitancy. There was no evidence for the widespread influence of mis-information, although broader vaccine hesitancy was associated with intentions to refuse COVID-19 vaccines (OR 20.60, 95% CI 14.20–30.30, p < 0.001). Low levels of trust in the decision-making (OR 1.63, 95% CI 1.08, 2.48, p = 0.021) and truthfulness (OR 8.76, 95% CI 4.15–19.90, p < 0.001) of the UK government were independently associated with higher odds of refusing COVID-19 vaccines. Compared to political centrists, conservatives and liberals were, respectively, more (OR 2.05, 95%CI 1.51–2.80, p < 0.001) and less (OR 0.30, 95% CI 0.22–0.41, p < 0.001) likely to refuse offered vaccines. Those who were willing to be vaccinated cited both personal and public protection as reasons, with some alluding to having a sense of collective responsibility. Conclusion: Dominant narratives of COVID-19 vaccine hesitancy are misconceived as primarily being driven by misinformation. Key indicators of UK vaccine acceptance include prior behaviors, transparency of the scientific process of vaccine development, mistrust in science and leadership and individual political views. Vaccine programmes should leverage the sense of ...

BACKGROUND: The success of a government's COVID-19 control strategy relies on public trust and broad acceptance of response measures. We investigated public perceptions of the UK government's COVID-19 response, focusing on the relationship between trust and perceived transparency, during the first wave (April 2020) of the COVID-19 pandemic in the United Kingdom. METHODS: Anonymous survey data were collected (2020-04-06 to 2020-04-22) from 9,322 respondents, aged 20+ using an online questionnaire shared primarily through Facebook. We took an embedded-mixed-methods approach to data analysis. Missing data were imputed via multiple imputation. Binomial & multinomial logistic regression were used to detect associations between demographic characteristics and perceptions or opinions of the UK government's response to COVID-19. Structural topic modelling (STM), qualitative thematic coding of sub-sets of responses were then used to perform a thematic analysis of topics that were of interest to key demographic groups. RESULTS: Most respondents (95.1%) supported government enforcement of behaviour change. While 52.1% of respondents thought the government was making good decisions, differences were apparent across demographic groups, for example respondents from Scotland had lower odds of responding positively than respondents in London. Higher educational levels saw decreasing odds of having a positive opinion of the government response and decreasing household income associated with decreasing positive opinion. Of respondents who thought the government was not making good decisions 60% believed the economy was being prioritised over people and their health. Positive views on government decision-making were associated with positive views on government transparency about the COVID-19 response. Qualitative analysis about perceptions of government transparency highlighted five key themes: (1) the justification of opacity due to the condition of crisis, (2) generalised mistrust of politics, (3) concerns about the role of scientific evidence, (4) quality of government communication and (5) questions about political decision-making processes. CONCLUSION: Our study suggests that trust is not homogenous across communities, and that generalised mistrust, concerns about the transparent use and communication of evidence and insights into decision-making processes can affect perceptions of the government's pandemic response. We recommend targeted community engagement, tailored to the experiences of different groups and a new focus on accountability and openness around how decisions are made in the response to the UK COVID-19 pandemic.

BACKGROUND: The success of a government's COVID-19 control strategy relies on public trust and broad acceptance of response measures. We investigated public perceptions of the UK government's COVID-19 response, focusing on the relationship between trust and transparency, during the first wave (April 2020) of the COVID-19 pandemic in the United Kingdom. METHODS: Anonymous survey data were collected (2020-04-06 to 2020-04-22) from 9,322 respondents, aged 20+ using an online questionnaire. We took a mixed methods approach to data analysis, combining statistical analyses, structural topic modelling (STM) and qualitative thematic coding of a sub-set of responses. Missing data were imputed via multiple imputation. RESULTS: Most respondents (95.1%) supported government enforcement of behaviour change. While 52.1% of respondents thought the government was making good decisions, differences were apparent across demographic groups, for example respondents from Scotland had lower odds of responding positively than respondents in London. Higher educational levels saw decreasing odds of having a positive opinion of the government response and decreasing household income associated with decreasing positive opinion. Of respondents who thought the government was not making good decisions 60% believed the economy was being prioritised over people and their health. Positive views on government decision-making were associated with positive views on government transparency about the COVID-19 response. Qualitative analysis about government transparency highlighted five key themes: (1) the justification of opacity due to the condition of crisis, (2) generalised mistrust of politics, (3) concerns about the role of scientific evidence, (4) quality of government communication and (5) questions about political decision-making processes. CONCLUSION: We recommend targeted community engagement tailored to different groups' experiences and a focus on accountability and openness around how decisions are made in the response to the UK COVID-19 pandemic.

BACKGROUND: There is substantial burden of seasonal influenza in Kenya, which led the government to consider introducing a national influenza vaccination programme. Given the cost implications of a nationwide programme, local economic evaluation data are needed to inform policy on the design and benefits of influenza vaccination. We set out to estimate the cost-effectiveness of seasonal influenza vaccination in Kenya. METHODS: We fitted an age-stratified dynamic transmission model to active surveillance data from patients with influenza from 2010 to 2018. Using a societal perspective, we developed a decision tree cost-effectiveness model and estimated the incremental cost-effectiveness ratio (ICER) per disability-adjusted life year (DALY) averted for three vaccine target groups: children 6–23 months (strategy I), 2–5 years (strategy II) and 6–14 years (strategy III) with either the Southern Hemisphere influenza vaccine (Strategy A) or Northern Hemisphere vaccine (Strategy B) or both (Strategy C: twice yearly vaccination campaigns, or Strategy D: year-round vaccination campaigns). We assessed cost-effectiveness by calculating incremental net monetary benefits (INMB) using a willingness-to-pay (WTP) threshold of 1–51% of the annual gross domestic product per capita ($17–$872). RESULTS: The mean number of infections across all ages was 2–15 million per year. When vaccination was well timed to influenza activity, the annual mean ICER per DALY averted for vaccinating children 6–23 months ranged between $749 and $1385 for strategy IA, $442 and $1877 for strategy IB, $678 and $4106 for strategy IC and $1147 and $7933 for strategy ID. For children 2–5 years, it ranged between $945 and $1573 for strategy IIA, $563 and $1869 for strategy IIB, $662 and $4085 for strategy IIC, and $1169 and $7897 for strategy IID. For children 6–14 years, it ranged between $923 and $3116 for strategy IIIA, $1005 and $2223 for strategy IIIB, $883 and $4727 for strategy IIIC and $1467 and $6813 for strategy IIID. Overall, no vaccination ...

BACKGROUND: There is substantial burden of seasonal influenza in Kenya, which led the government to consider introducing a national influenza vaccination programme. Given the cost implications of a nationwide programme, local economic evaluation data are needed to inform policy on the design and benefits of influenza vaccination. We set out to estimate the cost-effectiveness of seasonal influenza vaccination in Kenya. METHODS: We fitted an age-stratified dynamic transmission model to active surveillance data from patients with influenza from 2010 to 2018. Using a societal perspective, we developed a decision tree cost-effectiveness model and estimated the incremental cost-effectiveness ratio (ICER) per disability-adjusted life year (DALY) averted for three vaccine target groups: children 6-23 months (strategy I), 2-5 years (strategy II) and 6-14 years (strategy III) with either the Southern Hemisphere influenza vaccine (Strategy A) or Northern Hemisphere vaccine (Strategy B) or both (Strategy C: twice yearly vaccination campaigns, or Strategy D: year-round vaccination campaigns). We assessed cost-effectiveness by calculating incremental net monetary benefits (INMB) using a willingness-to-pay (WTP) threshold of 1-51% of the annual gross domestic product per capita ($17-$872). RESULTS: The mean number of infections across all ages was 2-15 million per year. When vaccination was well timed to influenza activity, the annual mean ICER per DALY averted for vaccinating children 6-23 months ranged between $749 and $1385 for strategy IA, $442 and $1877 for strategy IB, $678 and $4106 for strategy IC and $1147 and $7933 for strategy ID. For children 2-5 years, it ranged between $945 and $1573 for strategy IIA, $563 and $1869 for strategy IIB, $662 and $4085 for strategy IIC, and $1169 and $7897 for strategy IID. For children 6-14 years, it ranged between $923 and $3116 for strategy IIIA, $1005 and $2223 for strategy IIIB, $883 and $4727 for strategy IIIC and $1467 and $6813 for strategy IIID. Overall, no vaccination strategy was cost-effective at the minimum ($17) and median ($445) WTP thresholds. Vaccinating children 6-23 months once a year had the highest mean INMB value at $872 (WTP threshold upper limit); however, this strategy had very low probability of the highest net benefit. CONCLUSION: Vaccinating children 6-23 months once a year was the most favourable vaccination option; however, the strategy is unlikely to be cost-effective given the current WTP thresholds.

Governments around the world have implemented non-pharmaceutical interventions (NPIs), e.g. physical distancing and travel restrictions, to limit the transmission of COVID-19. While lockdowns and physical distancing have proven effective for reducing COVID-19 transmission, there is still limited understanding of the degree to which these interventions impact disease transmission, and how they are reflected in measures of human behaviour. Further, there is a lack of understanding about how new sources of data can be used to monitor NPIs, where these data have the potential to augment existing disease surveillance and modelling efforts. In this study, we assess the relationship between indicators of human mobility, NPIs, and estimates of R(t), a real-time measure of the intensity of COVID-19 transmission in subnational districts of Ghana using a multilevel generalised linear mixed model. We demonstrate a relationship between reductions in human mobility and decreases in R(t) during the early stages of the COVID-19 epidemic in Ghana, and show how reductions in human mobility relate to increasing stringency of NPIs. We demonstrate the utility of combining local disease surveillance data with large scale human mobility data to augment existing surveillance capacity to estimate and monitor the effect of NPI policies.

AbstractBackgroundEthnic and religious minorities have been disproportionately affected by SARS-CoV-2 worldwide. The UK strictly-Orthodox Jewish community has been severely affected by the pandemic. This group shares characteristics with other ethnic minorities including larger family sizes, higher rates of household crowding and relative socioeconomic deprivation. We studied a UK strictly-Orthodox Jewish population to understand how COVID-19 had spread within this community.MethodsWe performed a household-focused cross-sectional SARS-CoV-2 serosurvey specific to three antigen targets. Randomly-selected households completed a standardised questionnaire and underwent serological testing with a multiplex assay for SARS-CoV-2 IgG antibodies. We report clinical illness and testing before the serosurvey, seroprevalence stratified by age and gender. We used random-effects models to identify factors associated with infection and antibody titres.FindingsA total of 343 households, consisting of 1,759 individuals, were recruited. Serum was available for 1,242 participants. The overall seroprevalence for SARS-CoV-2 was 64.3% (95% CI 61.6-67.0%). The lowest seroprevalence was 27.6% in children under 5 years and rose to 73.8% in secondary school children and 74% in adults. Antibody titres were higher in symptomatic individuals and declined over time since reported COVID-19 symptoms, with the decline more marked for nucleocapsid titres.InterpretationIn this tight-knit religious minority population in the UK, we report one of the highest SARS-CoV-2 seroprevalence levels in the world to date. In the context of this high force of infection, all age groups experienced a high burden of infection. Actions to reduce the burden of disease in this and other minority populations are urgently required.FundingThis work was jointly funded by UKRI and NIHR [COV0335; MR/V027956/1], a donation from the LSHTM Alumni COVID-19 response fund, HDR UK, the MRC and the Wellcome Trust. The funders had no role in the design, conduct or analysis of the study or the decision to publish. The authors have no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.Research In ContextEvidence before the studyIn January 2020, we searched PubMed for articles on rates of SARS-CoV-2 infection amongst ethnic minority groups and amongst the Jewish population. Search teams included "COVID-19", "SARS-CoV-2", seroprevalence, "ethnic minority", and "Jewish" with no language restrictions. We also searched UK government documents on SARS-CoV-2 infection amongst minority groups. By January 2020, a large number of authors had reported that ethnic minority groups experienced higher numbers of cases and increased hospitalisations due to COVID-19. A small number of articles provided evidence that strictly-Orthodox Jewish populations had experienced a high rate of SARS-CoV-2 infection but extremely limited data was available on overall population level rates of infection amongst specific ethnic minority population groups. There was also extremely limited data on rates of infection amongst young children from ethnic minority groups.Added value of the studyWe report findings from a population representative, household survey of SARS-CoV-2 infection amongst a UK strictly Orthodox Jewish population. We demonstrate an extremely high seroprevalence rate of SARS-CoV-2 in this population which is more than five times the estimated seroprevalence nationally and five times the estimated seroprevalence in London. In addition the large number of children in our survey, reflective of the underlying population structure, allows us to demonstrate that in this setting there is a significant burden of disease in all age groups with secondary school aged children having an equivalent seroprevalence to adults.Implications of the available evidenceOur data provide clear evidence of the markedly disproportionate impact of SARS-CoV-2 in minority populations. In this setting infection occurs at high rates across all age groups including pre-school, primary school and secondary school-age children. Contextually appropriate measures to specifically reduce the impact of SARS-CoV-2 amongst minority populations are urgently required.

BackgroundTo mitigate SARS-CoV-2 transmission risks from international air travellers, many countries implemented a combination of up to 14 days of self-quarantine upon arrival plus PCR testing in the early stages of the COVID-19 pandemic in 2020.AimTo assess the effectiveness of quarantine and testing of international travellers to reduce risk of onward SARS-CoV-2 transmission into a destination country in the pre-COVID-19 vaccination era.MethodsWe used a simulation model of air travellers arriving in the United Kingdom from the European Union or the United States, incorporating timing of infection stages while varying quarantine duration and timing and number of PCR tests.ResultsQuarantine upon arrival with a PCR test on day 7 plus a 1-day delay for results can reduce the number of infectious arriving travellers released into the community by a median 94% (95% uncertainty interval (UI): 89-98) compared with a no quarantine/no test scenario. This reduction is similar to that achieved by a 14-day quarantine period (median > 99%; 95% UI: 98-100). Even shorter quarantine periods can prevent a substantial amount of transmission; all strategies in which travellers spend at least 5 days (mean incubation period) in quarantine and have at least one negative test before release are highly effective (median reduction 89%; 95% UI: 83-95)).ConclusionThe effect of different screening strategies impacts asymptomatic and symptomatic individuals differently. The choice of an optimal quarantine and testing strategy for unvaccinated air travellers may vary based on the number of possible imported infections relative to domestic incidence.

Combinations of intense non-pharmaceutical interventions (lockdowns) were introduced worldwide to reduce SARS-CoV-2 transmission. Many governments have begun to implement exit strategies that relax restrictions while attempting to control the risk of a surge in cases. Mathematical modelling has played a central role in guiding interventions, but the challenge of designing optimal exit strategies in the face of ongoing transmission is unprecedented. Here, we report discussions from the Isaac Newton Institute 'Models for an exit strategy' workshop (11–15 May 2020). A diverse community of modellers who are providing evidence to governments worldwide were asked to identify the main questions that, if answered, would allow for more accurate predictions of the effects of different exit strategies. Based on these questions, we propose a roadmap to facilitate the development of reliable models to guide exit strategies. This roadmap requires a global collaborative effort from the scientific community and policymakers, and has three parts: (i) improve estimation of key epidemiological parameters; (ii) understand sources of heterogeneity in populations; and (iii) focus on requirements for data collection, particularly in low-to-middle-income countries. This will provide important information for planning exit strategies that balance socio-economic benefits with public health.

BACKGROUND: By January, 2016, all known transmission chains of the Ebola virus disease (EVD) outbreak in west Africa had been stopped. However, there is concern about persistence of Ebola virus in the reproductive tract of men who have survived EVD. We aimed to use biostatistical modelling to describe the dynamics of Ebola virus RNA load in seminal fluid, including clearance parameters. METHODS: In this longitudinal study, we recruited men who had been discharged from three Ebola treatment units in Guinea between January and July, 2015. Participants provided samples of seminal fluid at follow-up every 3-6 weeks, which we tested for Ebola virus RNA using quantitative real-time RT-PCR. Representative specimens from eight participants were then inoculated into immunodeficient mice to test for infectivity. We used a linear mixed-effect model to analyse the dynamics of virus persistence in seminal fluid over time. FINDINGS: We enrolled 26 participants and tested 130 seminal fluid specimens; median follow up was 197 days (IQR 187-209 days) after enrolment, which corresponded to 255 days (228-287) after disease onset. Ebola virus RNA was detected in 86 semen specimens from 19 (73%) participants. Median duration of Ebola virus RNA detection was 158 days after onset (73-181; maximum 407 days at end of follow-up). Mathematical modelling of the quantitative time-series data showed a mean clearance rate of Ebola virus RNA from seminal fluid of -0·58 log units per month, although the clearance kinetic varied greatly between participants. Using our biostatistical model, we predict that 50% and 90% of male survivors clear Ebola virus RNA from seminal fluid at 115 days (90% prediction interval 72-160) and 294 days (212-399) after disease onset, respectively. We also predicted that the number of men positive for Ebola virus RNA in affected countries would decrease from about 50 in January 2016, to fewer than 1 person by July, 2016. Infectious virus was detected in 15 of 26 (58%) specimens tested in mice. INTERPRETATION: Time to clearance of Ebola virus RNA from seminal fluid varies greatly between individuals and could be more than 13 months. Our predictions will assist in decision-making about surveillance and preventive measures in EVD outbreaks. FUNDING: This study was funded by European Union's Horizon 2020 research and innovation programme, Directorate-General for International Cooperation and Development of the European Commission, Institut national de la santé et de la recherche médicale (INSERM), German Research Foundation (DFG), and Innovative Medicines Initiative 2 Joint Undertaking.