Although randomized placebo-controlled trials (RCT) are critical to establish efficacy of vaccines at the time of licensure, important remaining questions about vaccine effectiveness (VE)-used here ...to include individual-level measures and population-wide impact of vaccine programmes-can only be answered once the vaccine is in use, from observational studies. However, such studies are inherently at risk for bias. Using a causal framework and illustrating with examples, we review newer approaches to detecting and avoiding confounding and selection bias in three major classes of observational study design: cohort, case-control and ecological studies. Studies of influenza VE, especially in seniors, are an excellent demonstration of the challenges of detecting and reducing such bias, and so we use influenza VE as a running example. We take a fresh look at the time-trend studies often dismissed as 'ecological'. Such designs are the only observational study design that can measure the overall effect of a vaccination programme indirect (herd) as well as direct effects, and are in fact already an important part of the evidence base for several vaccines currently in use. Despite the great strides towards more robust observational study designs, challenges lie ahead for evaluating best practices for achieving robust unbiased results from observational studies. This is critical for evaluation of national and global vaccine programme effectiveness.
Highlights • We introduce a generalized-growth model to characterize epidemic growth. • The generalized-growth model capture sub-exponential and exponential epidemic growth. • We uncovered epidemic ...profiles from data ranging from very slow growth to near exponential growth. • Our findings reveal significant variation in epidemic growth patterns across outbreaks. • Findings indicate that sub-exponential growth dynamics is a common phenomenon.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We devote a special issue of the Journal of Infectious Diseases to review the recent advances of big data in strengthening disease surveillance, monitoring medical adverse events, informing ...transmission models, and tracking patient sentiments and mobility. We consider a broad definition of big data for public health, one encompassing patient information gathered from high-volume electronic health records and participatory surveillance systems, as well as mining of digital traces such as social media, Internet searches, and cell-phone logs. We introduce nine independent contributions to this special issue and highlight several cross-cutting areas that require further research, including representativeness, biases, volatility, and validation, and the need for robust statistical and hypotheses-driven analyses. Overall, we are optimistic that the big-data revolution will vastly improve the granularity and time-liness of available epidemiological information, with hybrid systems augmenting rather than supplanting traditional surveillance systems, and better prospects for accurate infectious diseases models and forecasts.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Cancer is considered a risk factor for COVID-19 mortality, yet several countries have reported that deaths with a primary code of cancer remained within historic levels during the COVID-19 pandemic. ...Here, we further elucidate the relationship between cancer mortality and COVID-19 on a population level in the US. We compared pandemic-related mortality patterns from underlying and multiple cause (MC) death data for six types of cancer, diabetes, and Alzheimer’s. Any pandemic-related changes in coding practices should be eliminated by study of MC data. Nationally in 2020, MC cancer mortality rose by only 3% over a pre-pandemic baseline, corresponding to ~13,600 excess deaths. Mortality elevation was measurably higher for less deadly cancers (breast, colorectal, and hematological, 2–7%) than cancers with a poor survival rate (lung and pancreatic, 0–1%). In comparison, there was substantial elevation in MC deaths from diabetes (37%) and Alzheimer’s (19%). To understand these differences, we simulated the expected excess mortality for each condition using COVID-19 attack rates, life expectancy, population size, and mean age of individuals living with each condition. We find that the observed mortality differences are primarily explained by differences in life expectancy, with the risk of death from deadly cancers outcompeting the risk of death from COVID-19.
Establishing the true death toll of a pandemic like COVID-19 is difficult, as laboratory testing is generally too limited to directly count the number of deaths that can be attributed to a particular pathogen. To overcome this, researchers analyse excess mortality – that is, they compare the observed number of deaths with the expected level based on trends in prior years. These techniques have been used for over 100 years to estimate the burden of pandemic influenza and became a popular way to estimate deaths due to the COVID-19 pandemic. Excess mortality can also reveal the impact of COVID-19 on sub-populations with chronic conditions. For example, previous studies showed that deaths with diabetes, heart disease and Alzheimer’s disease listed as the primary cause of death increased during waves of COVID-19. Cancer deaths did not show such a pattern, however, despite some epidemiological studies identifying cancer as a risk factor for COVID-19 mortality. To understand why this may be the case, Hansen et al. reviewed death certificates from different states in the United States during the first year of the pandemic. Their analyses of multiple-cause death records (listing cancer anywhere on the death certificate, not just as the primary cause of death) showed that death certificate coding practices during the pandemic did not explain the absence of excess cancer mortality. While a low level of excess mortality was detectable for cancers with longer life expectancy (breast cancer, for example), no elevation was observed for cancers with lower life expectancy, such as pancreatic cancer. The analyses demonstrate that the lack of excess mortality for especially deadly cancers can be explained through competing risks – in other words, the high risk of dying from the cancer itself vastly outweighs the additional risk posed by COVID-19. These findings shed light on how competing mortality risks might mask the true impact of COVID-19 on cancer mortality and explain the apparent discrepancy between cohort studies and excess mortality studies. To fully comprehend the impact of COVID-19 on patients living with cancers, future research should look at the possibility of longer-term increases in cancer mortality due to late diagnosis during pandemic lockdowns, and an elevated risk of severe illness.
Increasing evidence indicates that superspreading plays a dominant role in COVID-19 transmission. Recent estimates suggest that the dispersion parameter
for severe acute respiratory syndrome ...coronavirus 2 (SARS-CoV-2) is on the order of 0.1, which corresponds to about 10% of cases being the source of 80% of infections. To investigate how overdispersion might affect the outcome of various mitigation strategies, we developed an agent-based model with a social network that allows transmission through contact in three sectors: "close" (a small, unchanging group of mutual contacts as might be found in a household), "regular" (a larger, unchanging group as might be found in a workplace or school), and "random" (drawn from the entire model population and not repeated regularly). We assigned individual infectivity from a gamma distribution with dispersion parameter
We found that when
was low (i.e., greater heterogeneity, more superspreading events), reducing random sector contacts had a far greater impact on the epidemic trajectory than did reducing regular contacts; when
was high (i.e., less heterogeneity, no superspreading events), that difference disappeared. These results suggest that overdispersion of COVID-19 transmission gives the virus an Achilles' heel: Reducing contacts between people who do not regularly meet would substantially reduce the pandemic, while reducing repeated contacts in defined social groups would be less effective.
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Until recently, the World Health Organization (WHO) estimated the annual mortality burden of influenza to be 250 000 to 500 000 all-cause deaths globally; however, a 2017 study indicated a ...substantially higher mortality burden, at 290 000-650 000 influenza-associated deaths from respiratory causes alone, and a 2019 study estimated 99 000-200 000 deaths from lower respiratory tract infections directly caused by influenza. Here we revisit global and regional estimates of influenza mortality burden and explore mortality trends over time and geography.
We compiled influenza-associated excess respiratory mortality estimates for 31 countries representing 5 WHO regions during 2002-2011. From these we extrapolated the influenza burden for all 193 countries of the world using a multiple imputation approach. We then used mixed linear regression models to identify factors associated with high seasonal influenza mortality burden, including influenza types and subtypes, health care and socio-demographic development indicators, and baseline mortality levels.
We estimated an average of 389 000 (uncertainty range 294 000-518
000) respiratory deaths were associated with influenza globally each year during the study period, corresponding to ~ 2% of all annual respiratory deaths. Of these, 67% were among people 65 years and older. Global burden estimates were robust to the choice of countries included in the extrapolation model. For people <65 years, higher baseline respiratory mortality, lower level of access to health care and seasons dominated by the A(H1N1)pdm09 subtype were associated with higher influenza-associated mortality, while lower level of socio-demographic development and A(H3N2) dominance was associated with higher influenza mortality in adults ≥65 years.
Our global estimate of influenza-associated excess respiratory mortality is consistent with the 2017 estimate, despite a different modelling strategy, and the lower 2019 estimate which only captured deaths directly caused by influenza. Our finding that baseline respiratory mortality and access to health care are associated with influenza-related mortality in persons <65 years suggests that health care improvements in low and middle-income countries might substantially reduce seasonal influenza mortality. Our estimates add to the body of evidence on the variation in influenza burden over time and geography, and begin to address the relationship between influenza-associated mortality, health and development.
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NUK, OILJ, UL, UM, UPUK, VSZLJ
Superspreading is known to have played an important role in the transmission dynamics of SARS-CoV-2. In this Comment, the authors discuss how knowledge of the extent and cause of superspreading is ...important for designing appropriate control measures for emerging infectious diseases.The superspreading that characterized SARS and now COVID-19 can be rapidly quantified; however, its implications for outbreak control were never well understood. Recent studies point to its profound impact on outbreak dynamics and prospects for effective control of a future Disease X. These insights necessitate research into the mechanisms, impact and different modes of superspreading more widely.
The goal of influenza-like illness (ILI) surveillance is to determine the timing, location and magnitude of outbreaks by monitoring the frequency and progression of clinical case incidence. Advances ...in computational and information technology have allowed for automated collection of higher volumes of electronic data and more timely analyses than previously possible. Novel surveillance systems, including those based on internet search query data like Google Flu Trends (GFT), are being used as surrogates for clinically-based reporting of influenza-like-illness (ILI). We investigated the reliability of GFT during the last decade (2003 to 2013), and compared weekly public health surveillance with search query data to characterize the timing and intensity of seasonal and pandemic influenza at the national (United States), regional (Mid-Atlantic) and local (New York City) levels. We identified substantial flaws in the original and updated GFT models at all three geographic scales, including completely missing the first wave of the 2009 influenza A/H1N1 pandemic, and greatly overestimating the intensity of the A/H3N2 epidemic during the 2012/2013 season. These results were obtained for both the original (2008) and the updated (2009) GFT algorithms. The performance of both models was problematic, perhaps because of changes in internet search behavior and differences in the seasonality, geographical heterogeneity and age-distribution of the epidemics between the periods of GFT model-fitting and prospective use. We conclude that GFT data may not provide reliable surveillance for seasonal or pandemic influenza and should be interpreted with caution until the algorithm can be improved and evaluated. Current internet search query data are no substitute for timely local clinical and laboratory surveillance, or national surveillance based on local data collection. New generation surveillance systems such as GFT should incorporate the use of near-real time electronic health data and computational methods for continued model-fitting and ongoing evaluation and improvement.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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