Correction: Recommended reporting items for epidemic forecasting and prediction research: The EPIFORGE 2020 guidelines.

[This corrects the article DOI: 10.1371/journal.pmed.1003793.].

Superspreading events in the transmission dynamics of SARS-CoV-2: Opportunities for interventions and control.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the etiological agent of the Coronavirus Disease 2019 (COVID-19) disease, has moved rapidly around the globe, infecting millions and killing hundreds of thousands. The basic reproduction number, which has been widely used-appropriately and less appropriately-to characterize the transmissibility of the virus, hides the fact that transmission is stochastic, often dominated by a small number of individuals, and heavily influenced by superspreading events (SSEs). The distinct transmission features of SARS-CoV-2, e.g., high stochasticity under low prevalence (as compared to other pathogens, such as influenza), and the central role played by SSEs on transmission dynamics cannot be overlooked. Many explosive SSEs have occurred in indoor settings, stoking the pandemic and shaping its spread, such as long-term care facilities, prisons, meat-packing plants, produce processing facilities, fish factories, cruise ships, family gatherings, parties, and nightclubs. These SSEs demonstrate the urgent need to understand routes of transmission, while posing an opportunity to effectively contain outbreaks with targeted interventions to eliminate SSEs. Here, we describe the different types of SSEs, how they influence transmission, empirical evidence for their role in the COVID-19 pandemic, and give recommendations for control of SARS-CoV-2.

Recommended reporting items for epidemic forecasting and prediction research: The EPIFORGE 2020 guidelines.

BACKGROUND: The importance of infectious disease epidemic forecasting and prediction research is underscored by decades of communicable disease outbreaks, including COVID-19. Unlike other fields of medical research, such as clinical trials and systematic reviews, no reporting guidelines exist for reporting epidemic forecasting and prediction research despite their utility. We therefore developed the EPIFORGE checklist, a guideline for standardized reporting of epidemic forecasting research. METHODS AND FINDINGS: We developed this checklist using a best-practice process for development of reporting guidelines, involving a Delphi process and broad consultation with an international panel of infectious disease modelers and model end users. The objectives of these guidelines are to improve the consistency, reproducibility, comparability, and quality of epidemic forecasting reporting. The guidelines are not designed to advise scientists on how to perform epidemic forecasting and prediction research, but rather to serve as a standard for reporting critical methodological details of such studies. CONCLUSIONS: These guidelines have been submitted to the EQUATOR network, in addition to hosting by other dedicated webpages to facilitate feedback and journal endorsement.

Asymptomatic Infection and Transmission of Pertussis in Households: A Systematic Review.

We conducted a systematic review to describe the frequency of mild, atypical, and asymptomatic infection among household contacts of pertussis cases and to explore the published literature for evidence of asymptomatic transmission. We included studies that obtained and tested laboratory specimens from household contacts regardless of symptom presentation and reported the proportion of cases with typical, mild/atypical, or asymptomatic infection. After screening 6789 articles, we included 26 studies. Fourteen studies reported household contacts with mild/atypical pertussis. These comprised up to 46.2% of all contacts tested. Twenty-four studies reported asymptomatic contacts with laboratory-confirmed pertussis, comprising up to 55.6% of those tested. Seven studies presented evidence consistent with asymptomatic pertussis transmission between household contacts. Our results demonstrate a high prevalence of subclinical infection in household contacts of pertussis cases, which may play a substantial role in the ongoing transmission of disease. Our review reveals a gap in our understanding of pertussis transmission.

Contributions from the silent majority dominate dengue virus transmission.

Despite estimates that, each year, as many as 300 million dengue virus (DENV) infections result in either no perceptible symptoms (asymptomatic) or symptoms that are sufficiently mild to go undetected by surveillance systems (inapparent), it has been assumed that these infections contribute little to onward transmission. However, recent blood-feeding experiments with Aedes aegypti mosquitoes showed that people with asymptomatic and pre-symptomatic DENV infections are capable of infecting mosquitoes. To place those findings into context, we used models of within-host viral dynamics and human demographic projections to (1) quantify the net infectiousness of individuals across the spectrum of DENV infection severity and (2) estimate the fraction of transmission attributable to people with different severities of disease. Our results indicate that net infectiousness of people with asymptomatic infections is 80% (median) that of people with apparent or inapparent symptomatic infections (95% credible interval (CI): 0-146%). Due to their numerical prominence in the infectious reservoir, clinically inapparent infections in total could account for 84% (CI: 82-86%) of DENV transmission. Of infections that ultimately result in any level of symptoms, we estimate that 24% (95% CI: 0-79%) of onward transmission results from mosquitoes biting individuals during the pre-symptomatic phase of their infection. Only 1% (95% CI: 0.8-1.1%) of DENV transmission is attributable to people with clinically detected infections after they have developed symptoms. These findings emphasize the need to (1) reorient current practices for outbreak response to adoption of pre-emptive strategies that account for contributions of undetected infections and (2) apply methodologies that account for undetected infections in surveillance programs, when assessing intervention impact, and when modeling mosquito-borne virus transmission.

Asymmetric percolation drives a double transition in sexual contact networks.

Zika virus (ZIKV) exhibits unique transmission dynamics in that it is concurrently spread by a mosquito vector and through sexual contact. Due to the highly asymmetric durations of infectiousness between males and females-it is estimated that males are infectious for periods up to 10 times longer than females-we show that this sexual component of ZIKV transmission behaves akin to an asymmetric percolation process on the network of sexual contacts. We exactly solve the properties of this asymmetric percolation on random sexual contact networks and show that this process exhibits two epidemic transitions corresponding to a core-periphery structure. This structure is not present in the underlying contact networks, which are not distinguishable from random networks, and emerges because of the asymmetric percolation. We provide an exact analytical description of this double transition and discuss the implications of our results in the context of ZIKV epidemics. Most importantly, our study suggests a bias in our current ZIKV surveillance, because the community most at risk is also one of the least likely to get tested.

Quantifying Public Interest in Police Reforms by Mining Internet Search Data Following George Floyd's Death.

BACKGROUND: The death of George Floyd while in police custody has resurfaced serious questions about police conduct that result in the deaths of unarmed persons. OBJECTIVE: Data-driven strategies that identify and prioritize the public's needs may engender a public health response to improve policing. We assessed how internet searches indicative of interest in police reform changed after Mr Floyd's death. METHODS: We monitored daily Google searches (per 10 million total searches) that included the terms "police" and "reform(s)" (eg, "reform the police," "best police reforms," etc) originating from the United States between January 1, 2010, through July 5, 2020. We also monitored searches containing the term "police" with "training," "union(s)," "militarization," or "immunity" as markers of interest in the corresponding reform topics. RESULTS: The 41 days following Mr Floyd's death corresponded with the greatest number of police "reform(s)" searches ever recorded, with 1,350,000 total searches nationally. Searches increased significantly in all 50 states and Washington DC. By reform topic, nationally there were 1,220,000 total searches for "police" and "union(s)"; 820,000 for "training"; 360,000 for "immunity"; and 72,000 for "militarization." In terms of searches for all policy topics by state, 33 states searched the most for "training," 16 for "union(s)," and 2 for "immunity." States typically in the southeast had fewer queries related to any police reform topic than other states. States that had a greater percentage of votes for President Donald Trump during the 2016 election searched more often for police "union(s)" while states favoring Secretary Hillary Clinton searched more for police "training." CONCLUSIONS: The United States is at a historical juncture, with record interest in topics related to police reform with variability in search terms across states. Policy makers can respond to searches by considering the policies their constituencies are searching for online, notably police training and unions. Public health leaders can respond by engaging in the subject of policing and advocating for evidence-based policy reforms.

The risk of sustained sexual transmission of Zika is underestimated.

Pathogens often follow more than one transmission route during outbreaks-from needle sharing plus sexual transmission of HIV to small droplet aerosol plus fomite transmission of influenza. Thus, controlling an infectious disease outbreak often requires characterizing the risk associated with multiple mechanisms of transmission. For example, during the Ebola virus outbreak in West Africa, weighing the relative importance of funeral versus health care worker transmission was essential to stopping disease spread. As a result, strategic policy decisions regarding interventions must rely on accurately characterizing risks associated with multiple transmission routes. The ongoing Zika virus (ZIKV) outbreak challenges our conventional methodologies for translating case-counts into route-specific transmission risk. Critically, most approaches will fail to accurately estimate the risk of sustained sexual transmission of a pathogen that is primarily vectored by a mosquito-such as the risk of sustained sexual transmission of ZIKV. By computationally investigating a novel mathematical approach for multi-route pathogens, our results suggest that previous epidemic threshold estimates could under-estimate the risk of sustained sexual transmission by at least an order of magnitude. This result, coupled with emerging clinical, epidemiological, and experimental evidence for an increased risk of sexual transmission, would strongly support recent calls to classify ZIKV as a sexually transmitted infection.

Can a selfie promote public engagement with skin cancer?

Social media may provide new opportunities to promote skin cancer prevention, but research to understand this potential is needed. In April of 2015, Kentucky native Tawny Willoughby (TW) shared a graphic skin cancer selfie on Facebook that subsequently went viral. We examined the volume of comments and shares of her original Facebook post; news volume of skin cancer from Google News; and search volume for skin cancer Google queries. We compared these latter metrics after TWs announcement against expected volumes based on forecasts of historical trends. TWs skin cancer story was picked up by the media on May 11, 2015 after the social media post had been shared approximately 50,000 times. All search queries for skin cancer increased 162% (95% CI 102 to 320) and 155% (95% CI 107 to 353) on May 13th and 14th, when news about TW's skin cancer selfie was at its peak, and remained higher through May 17th. Google searches about skin cancer prevention and tanning were also significantly higher than expected volumes. In practical terms, searches reached near-record levels - i.e., May 13th, 14th and 15th were respectively the 6th, 8th, and 40th most searched days for skin cancer since January 1, 2004 when Google began tracking searches. We conclude that an ordinary person's social media post caught the public's imagination and led to significant increases in public engagement with skin cancer prevention. Digital surveillance methods can rapidly detect these events in near real time, allowing public health practitioners to engage and potentially elevate positive effects.

Complex dynamics of synergistic coinfections on realistically clustered networks.

We investigate the impact of contact structure clustering on the dynamics of multiple diseases interacting through coinfection of a single individual, two problems typically studied independently. We highlight how clustering, which is well known to hinder propagation of diseases, can actually speed up epidemic propagation in the context of synergistic coinfections if the strength of the coupling matches that of the clustering. We also show that such dynamics lead to a first-order transition in endemic states, where small changes in transmissibility of the diseases can lead to explosive outbreaks and regions where these explosive outbreaks can only happen on clustered networks. We develop a mean-field model of coinfection of two diseases following susceptible-infectious-susceptible dynamics, which is allowed to interact on a general class of modular networks. We also introduce a criterion based on tertiary infections that yields precise analytical estimates of when clustering will lead to faster propagation than nonclustered networks. Our results carry importance for epidemiology, mathematical modeling, and the propagation of interacting phenomena in general. We make a call for more detailed epidemiological data of interacting coinfections.

The Charlie Sheen Effect on Rapid In-home Human Immunodeficiency Virus Test Sales.

One in eight of the 1.2 million Americans living with human immunodeficiency virus (HIV) are unaware of their positive status, and untested individuals are responsible for most new infections. As a result, testing is the most cost-effective HIV prevention strategy and must be accelerated when opportunities are presented. Web searches for HIV spiked around actor Charlie Sheen's HIV-positive disclosure. However, it is unknown whether Sheen's disclosure impacted offline behaviors like HIV testing. The goal of this study was to determine if Sheen's HIV disclosure was a record-setting HIV prevention event and determine if Web searches presage increases in testing allowing for rapid detection and reaction in the future. Sales of OraQuick rapid in-home HIV test kits in the USA were monitored weekly from April 12, 2014, to April 16, 2016, alongside Web searches including the terms "test," "tests," or "testing" and "HIV" as accessed from Google Trends. Changes in OraQuick sales around Sheen's disclosure and prediction models using Web searches were assessed. OraQuick sales rose 95% (95% CI, 75-117; p < 0.001) of the week of Sheen's disclosure and remained elevated for 4 more weeks (p < 0.05). In total, there were 8225 more sales than expected around Sheen's disclosure, surpassing World AIDS Day by a factor of about 7. Moreover, Web searches mirrored OraQuick sales trends (r = 0.79), demonstrating their ability to presage increases in testing. The "Charlie Sheen effect" represents an important opportunity for a public health response, and in the future, Web searches can be used to detect and act on more opportunities to foster prevention behaviors.

Dengue Virus (DENV) Neutralizing Antibody Kinetics in Children After Symptomatic Primary and Postprimary DENV Infection.

The immune response to dengue virus (DENV) infection is complex and not fully understood. Using longitudinal data from 181 children with dengue in Thailand who were followed for up to 3 years, we describe neutralizing antibody kinetics following symptomatic DENV infection. We observed that antibody titers varied by serotype, homotypic vs heterotypic responses, and primary versus postprimary infections. The rates of change in antibody titers over time varied between primary and postprimary responses. For primary infections, titers increased from convalescence to 6 months. By comparing homotypic and heterotypic antibody titers, we saw an increase in type specificity from convalescence to 6 months for primary DENV3 infections but not primary DENV1 infections. In postprimary cases, there was a decrease in titers from convalescence up until 6 months after infection. Beginning 1 year after both primary and postprimary infections, there was evidence of increasing antibody titers, with greater increases in children with lower titers, suggesting that antibody titers were boosted due to infection and that higher levels of neutralizing antibody may be more likely to confer a sterilizing immune response. These findings may help to model virus transmission dynamics and provide baseline data to support the development of vaccines and therapeutics.

Eradicating infectious disease using weakly transmissible vaccines.

Viral vaccines have had remarkable positive impacts on human health as well as the health of domestic animal populations. Despite impressive vaccine successes, however, many infectious diseases cannot yet be efficiently controlled or eradicated through vaccination, often because it is impossible to vaccinate a sufficient proportion of the population. Recent advances in molecular biology suggest that the centuries-old method of individual-based vaccine delivery may be on the cusp of a major revolution. Specifically, genetic engineering brings to life the possibility of a live, transmissible vaccine. Unfortunately, releasing a highly transmissible vaccine poses substantial evolutionary risks, including reversion to high virulence as has been documented for the oral polio vaccine. An alternative, and far safer approach, is to rely on genetically engineered and weakly transmissible vaccines that have reduced scope for evolutionary reversion. Here, we use mathematical models to evaluate the potential efficacy of such weakly transmissible vaccines. Our results demonstrate that vaccines with even a modest ability to transmit can significantly lower the incidence of infectious disease and facilitate eradication efforts. Consequently, weakly transmissible vaccines could provide an important tool for controlling infectious disease in wild and domestic animal populations and for reducing the risks of emerging infectious disease in humans.

The Role of Fear-Related Behaviors in the 2013-2016 West Africa Ebola Virus Disease Outbreak.

The 2013-2016 West Africa Ebola virus disease pandemic was the largest, longest, deadliest, and most geographically expansive outbreak in the 40-year interval since Ebola was first identified. Fear-related behaviors played an important role in shaping the outbreak. Fear-related behaviors are defined as "individual or collective behaviors and actions initiated in response to fear reactions that are triggered by a perceived threat or actual exposure to a potentially traumatizing event. FRBs modify the future risk of harm." This review examines how fear-related behaviors were implicated in (1) accelerating the spread of Ebola, (2) impeding the utilization of life-saving Ebola treatment, (3) curtailing the availability of medical services for treatable conditions, (4) increasing the risks for new-onset psychological distress and psychiatric disorders, and (5) amplifying the downstream cascades of social problems. Fear-related behaviors are identified for each of these outcomes. Particularly notable are behaviors such as treating Ebola patients in home or private clinic settings, the "laying of hands" on Ebola-infected individuals to perform faith-based healing, observing hands-on funeral and burial customs, foregoing available life-saving treatment, and stigmatizing Ebola survivors and health professionals. Future directions include modeling the onset, operation, and perpetuation of fear-related behaviors and devising strategies to redirect behavioral responses to mass threats in a manner that reduces risks and promotes resilience.

Asymptomatic transmission and the resurgence of Bordetella pertussis.

BACKGROUND: The recent increase in whooping cough incidence (primarily caused by Bordetella pertussis) presents a challenge to both public health practitioners and scientists trying to understand the mechanisms behind its resurgence. Three main hypotheses have been proposed to explain the resurgence: 1) waning of protective immunity from vaccination or natural infection over time, 2) evolution of B. pertussis to escape protective immunity, and 3) low vaccine coverage. Recent studies have suggested a fourth mechanism: asymptomatic transmission from individuals vaccinated with the currently used acellular B. pertussis vaccines. METHODS: Using wavelet analyses of B. pertussis incidence in the United States (US) and United Kingdom (UK) and a phylodynamic analysis of 36 clinical B. pertussis isolates from the US, we find evidence in support of asymptomatic transmission of B. pertussis. Next, we examine the clinical, public health, and epidemiological consequences of asymptomatic B. pertussis transmission using a mathematical model. RESULTS: We find that: 1) the timing of changes in age-specific attack rates observed in the US and UK are consistent with asymptomatic transmission; 2) the phylodynamic analysis of the US sequences indicates more genetic diversity in the overall bacterial population than would be suggested by the observed number of infections, a pattern expected with asymptomatic transmission; 3) asymptomatic infections can bias assessments of vaccine efficacy based on observations of B. pertussis-free weeks; 4) asymptomatic transmission can account for the observed increase in B. pertussis incidence; and 5) vaccinating individuals in close contact with infants too young to receive the vaccine ("cocooning" unvaccinated children) may be ineffective. CONCLUSIONS: Although a clear role for the previously suggested mechanisms still exists, asymptomatic transmission is the most parsimonious explanation for many of the observations surrounding the resurgence of B. pertussis in the US and UK. These results have important implications for B. pertussis vaccination policy and present a complicated scenario for achieving herd immunity and B. pertussis eradication.

US consumer interest in non-cigarette tobacco products spikes around the 2009 federal tobacco tax increase.

OBJECTIVES: This quasi-experimental longitudinal study monitored aggregate Google search queries as a proxy for consumer interest in non-cigarette tobacco products (NTP) around the time of the 2009 US federal tobacco tax increase. METHODS: Query trends for searches mentioning common NTP were downloaded from Google's public archives. The mean relative increase was estimated by comparing the observed with expected query volume for the 16 weeks around the tax. RESULTS: After the tax was announced, queries spiked for chewing tobacco, cigarillos, electronic cigarettes ('e-cigarettes'), roll-your-own (RYO) tobacco, snuff, and snus. E-cigarette queries were 75% (95% CI 70% to 80%) higher than expected 8 weeks before and after the tax, followed by RYO 59% (95% CI 53% to 65%), snus 34% (95% CI 31% to 37%), chewing tobacco 17% (95% CI 15% to 20%), cigarillos 14% (95% CI 11% to 17%), and snuff 13% (95% CI 10% to 14%). Unique queries increasing the most were 'ryo cigarettes' 427% (95% CI 308% to 534%), 'ryo tobacco' 348% (95% CI 300% to 391%), 'best electronic cigarette' 221% (95% CI 185% to 257%), and 'e-cigarette' 205% (95% CI 163% to 245%). CONCLUSIONS: The 2009 tobacco tax increase triggered large increases in consumer interest for some NTP, particularly e-cigarettes and RYO tobacco.

The timing and targeting of treatment in influenza pandemics influences the emergence of resistance in structured populations.

Antiviral resistance in influenza is rampant and has the possibility of causing major morbidity and mortality. Previous models have identified treatment regimes to minimize total infections and keep resistance low. However, the bulk of these studies have ignored stochasticity and heterogeneous contact structures. Here we develop a network model of influenza transmission with treatment and resistance, and present both standard mean-field approximations as well as simulated dynamics. We find differences in the final epidemic sizes for identical transmission parameters (bistability) leading to different optimal treatment timing depending on the number initially infected. We also find, contrary to previous results, that treatment targeted by number of contacts per individual (node degree) gives rise to more resistance at lower levels of treatment than non-targeted treatment. Finally we highlight important differences between the two methods of analysis (mean-field versus stochastic simulations), and show where traditional mean-field approximations fail. Our results have important implications not only for the timing and distribution of influenza chemotherapy, but also for mathematical epidemiological modeling in general. Antiviral resistance in influenza may carry large consequences for pandemic mitigation efforts, and models ignoring contact heterogeneity and stochasticity may provide misleading policy recommendations.

Do celebrity cancer diagnoses promote primary cancer prevention?

OBJECTIVE: Celebrity cancer diagnoses generate considerable media coverage of and increase interest in cancer screening, but do they also promote primary cancer prevention? METHODS: Daily trends for smoking cessation-related media (information-availability) and Google queries (information-seeking) around Brazilian President and smoker Lula da Silva's laryngeal cancer diagnosis announcements were compared to a typical period and several cessation awareness events. RESULTS: Cessation media coverage was 163% (95% confidence interval, 54-328) higher than expected the week after the announcement but returned to typical levels the second week. Cessation queries were 67% (95% confidence interval, 40-96) greater the week after Lula's announcement, remaining 153% (95% confidence interval, 121-188), 130% (95% confidence interval, 101-163) and 71% (95% confidence interval, 43-100) greater during the second, third, and fourth week after the announcement. There were 1.1 million excess cessation queries the month after Lula's announcement, eclipsing query volumes for the week around New Years Day, World No Tobacco Day, and Brazilian National No Smoking Day. CONCLUSION: Just as celebrity diagnoses promote cancer screening, they may also promote primary prevention. Discovery of this dynamic suggests the public should be further encouraged to consider primary (in addition to the usual secondary) cancer prevention around celebrity diagnoses, though more cases, cancers, and prevention behaviors must be explored.

Digital detection for tobacco control: online reactions to the 2009 U.S. cigarette excise tax increase.

INTRODUCTION: The Internet is revolutionizing tobacco control, but few have harnessed the Web for surveillance. We demonstrate for the first time an approach for analyzing aggregate Internet search queries that captures precise changes in population considerations about tobacco. METHODS: We compared tobacco-related Google queries originating in the United States during the week of the State Children's Health Insurance Program (SCHIP) 2009 cigarette excise tax increase with a historic baseline. Specific queries were then ranked according to their relative increases while also considering approximations of changes in absolute search volume. RESULTS: Individual queries with the largest relative increases the week of the SCHIP tax were "cigarettes Indian reservations" 640% (95% CI, 472-918), "free cigarettes online" 557% (95% CI, 432-756), and "Indian reservations cigarettes" 542% (95% CI, 414-733), amounting to about 7,500 excess searches. By themes, the largest relative increases were tribal cigarettes 246% (95% CI, 228-265), "free" cigarettes 215% (95% CI, 191-242), and cigarette stores 176% (95% CI, 160-193), accounting for 21,000, 27,000, and 90,000 excess queries. All avoidance queries, including those aforementioned themes, relatively increased 150% (95% CI, 144-155) or 550,000 from their baseline. All cessation queries increased 46% (95% CI, 44-48), or 175,000, around SCHIP; including themes for "cold turkey" 19% (95% CI, 11-27) or 2,600, cessation products 47% (95% CI, 44-50) or 78,000, and dubious cessation approaches (e.g., hypnosis) 40% (95% CI, 33-47) or 2,300. CONCLUSIONS: The SCHIP tax motivated specific changes in population considerations. Our strategy can support evaluations that temporally link tobacco control measures with instantaneous population reactions, as well as serve as a springboard for traditional studies, for example, including survey questionnaire design.