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Epidemic data are often difficult to interpret due to inconsistent detection and reporting. As these data are critically relied upon to inform policy and epidemic projections, understanding reporting trends is similarly important. Early reporting of the COVID-19 pandemic in particular is complicated, due to changing diagnostic and testing protocols. An internal audit by the State of Florida, USA found numerous specific examples of irregularities in COVID-19 case and death reports. Using case, hospitalization, and death data from the the first year of the COVID-19 pandemic in Florida, we present approaches that can be used to identify the timing, direction, and magnitude of some reporting changes. Specifically, by establishing a baseline of detection probabilities from the first (spring) wave, we show that transmission trends among all age groups were similar, with the exception of the second summer wave, when younger people became infected earlier than seniors, by approximately 2 weeks. We also found a substantial drop in case-fatality risk (CFR) among all age groups over the three waves during the first year of the pandemic, with the most drastic changes seen in the 0 to 39 age group. The CFR trends provide useful insights into infection detection that would not be possible by relying on the number of tests alone. During the third wave, for which we have reliable hospitalization data, the CFR was remarkably stable across all age groups. In contrast, the hospitalization-to-case ratio varied inversely with cases while the death-to-hospitalization ratio varied proportionally. Although specific trends are likely to vary between locales, the approaches we present here offer a generic way to understand the substantial changes that occurred in the relationships among the key epidemic indicators. [ABSTRACT FROM AUTHOR]

Access to COVID-19 vaccines on the global scale has been drastically hindered by structural socio-economic disparities. Here, we develop a data-driven, age-stratified epidemic model to evaluate the effects of COVID-19 vaccine inequities in twenty lower middle and low income countries (LMIC) selected from all WHO regions. We investigate and quantify the potential effects of higher or earlier doses availability. In doing so, we focus on the crucial initial months of vaccine distribution and administration, exploring counterfactual scenarios where we assume the same per capita daily vaccination rate reported in selected high income countries. We estimate that more than 50% of deaths (min-max range: [54−94%]) that occurred in the analyzed countries could have been averted. We further consider scenarios where LMIC had similarly early access to vaccine doses as high income countries. Even without increasing the number of doses, we estimate an important fraction of deaths (min-max range: [6−50%]) could have been averted. In the absence of the availability of high-income countries, the model suggests that additional non-pharmaceutical interventions inducing a considerable relative decrease of transmissibility (min-max range: [15−70%]) would have been required to offset the lack of vaccines. Overall, our results quantify the negative impacts of vaccine inequities and underscore the need for intensified global efforts devoted to provide faster access to vaccine programs in low and lower-middle-income countries. Global COVID-19 vaccine distribution has been inequitable. In this mathematical modelling study, the authors estimate the proportion of deaths that could have been averted in twenty low- and lower-middle-income countries if vaccines had been more widely available early in the pandemic. [ABSTRACT FROM AUTHOR]

Transmission trees can be established through detailed contact histories, statistical or phylogenetic inference, or a combination of methods. Each approach has its limitations, and the extent to which they succeed in revealing a 'true' transmission history remains unclear. In this study, we compared the transmission trees obtained through contact tracing investigations and various inference methods to identify the contribution and value of each approach. We studied eighty-six sequenced cases reported in Guinea between March and November 2015. Contact tracing investigations classified these cases into eight independent transmission chains. We inferred the transmission history from the genetic sequences of the cases (phylogenetic approach), their onset date (epidemiological approach), and a combination of both (combined approach). The inferred transmission trees were then compared to those from the contact tracing investigations. Inference methods using individual data sources (i.e. the phylogenetic analysis and the epidemiological approach) were insufficiently informative to accurately reconstruct the transmission trees and the direction of transmission. The combined approach was able to identify a reduced pool of infectors for each case and highlight likely connections among chains classified as independent by the contact tracing investigations. Overall, the transmissions identified by the contact tracing investigations agreed with the evolutionary history of the viral genomes, even though some cases appeared to be misclassified. Therefore, collecting genetic sequences during outbreak is key to supplement the information contained in contact tracing investigations. Although none of the methods we used could identify one unique infector per case, the combined approach highlighted the added value of mixing epidemiological and genetic information to reconstruct who infected whom. [ABSTRACT FROM AUTHOR]

Introduction The emergence and global spread of a novel strain of human influenza A/H1N1 during 2009 (pandemic [H1N1] 2009 influenza, or H1N1pdm) has highlighted the importance of data from both [...]

Detailed characterization of severe acute respiratory syndrome coronavirus 2 (SARSCoV- 2) transmission across different settings can help design less disruptive interventions. We used real-time, privacy-enhanced mobility data in the New York City, NY and Seattle, WA metropolitan areas to build a detailed agent-based model of SARS-CoV-2 infection to estimate the where, when, and magnitude of transmission events during the pandemic's first wave. We estimate that only 18% of individuals produce most infections (80%), with about 10% of events that can be considered superspreading events (SSEs). Although mass gatherings present an important risk for SSEs, we estimate that the bulk of transmission occurred in smaller events in settings like workplaces, grocery stores, or food venues. The places most important for transmission change during the pandemic and are different across cities, signaling the large underlying behavioral component underneath them. Our modeling complements case studies and epidemiological data and indicates that real-time tracking of transmission events could help evaluate and define targeted mitigation policies. [ABSTRACT FROM AUTHOR]

Background Although advances in rehydration therapy have made cholera a treatable disease with low case-fatality in settings with appropriate medical care, cholera continues to impose considerable mortality in the world's most impoverished populations. Internationally licensed, killed whole-cell based oral cholera vaccines (OCVs) have been available for over a decade, but have not been used for the control of cholera. Recently, these vaccines were shown to confer significant levels of herd protection, suggesting that the protective potential of these vaccines has been underestimated and that these vaccines may be highly effective in cholera control when deployed in mass immunization programs. We used a large-scale stochastic simulation model to investigate the possibility of controlling endemic cholera with OCVs. Methods and Findings We construct a large-scale, stochastic cholera transmission model of Matlab, Bangladesh. We find that cholera transmission could be controlled in endemic areas with 50% coverage with OCVs. At this level of coverage, the model predicts that there would be an 89% (95% confidence interval [CI] 72%-98%) reduction in cholera cases among the unvaccinated, and a 93% (95% CI 82%-99%) reduction overall in the entire population. Even a more modest coverage of 30% would result in a 76% (95% CI 44%-95%) reduction in cholera incidence for the population area covered. For populations that have less natural immunity than the population of Matlab, 70% coverage would probably be necessary for cholera control, i.e., an annual incidence rate of [less than or equal to] 1 case per 1,000 people in the population. Conclusions Endemic cholera could be reduced to an annual incidence rate of ≤ 1 case per 1,000 people in endemic areas with biennial vaccination with OCVs if coverage could reach 50%-70% depending on the level of prior immunity in the population. These vaccination efforts could be targeted with careful use of ecological data., Introduction The global burden of cholera remains substantial. In 2005, 131,943 cases and 2,272 deaths were reported to the WHO, and recently major, sustained epidemics have been reported in West [...]

Highly pathogenic avian influenza A (subtype H5N1) is threatening to cause a human pandemic of potentially devastating proportions. We used a stochastic influenza simulation mode[ for rural Southeast Asia to investigate the effectiveness of targeted antiviral prophylaxis, quarantine, and pre-vaccination in containing an emerging influenza strain at the source. If the basic reproductive number ([R.sub.0]) was below 1.60, our simulations showed that a prepared response with targeted antivirals would have a high probability of containing the disease. In that case, an antiviral agent stockpile on the order of 100,000 to 1 million courses for treatment and prophylaxis would be sufficient. If pre-vaccination occurred, then targeted antiviral prophylaxis could be effective for containing strains with an [R.sub.0] as high as 2.1. Combinations of targeted antiviral prophylaxis, pre-vaccination, and quarantine could contain strains with an [R.sub.0] as high as 2.4., The world may be on the brink of an influenza pandemic (1-4). Avian influenza A (subtype H5N1) is causing widespread outbreaks among poultry in Southeast (SE) Asia, with sporadic transmission [...]

The need for a planned response to a deliberate introduction of smallpox has recently become urgent. We constructed a stochastic simulator of the spread of smallpox in structured communities to compare the effectiveness of mass vaccination versus targeted vaccination of close contacts of cases. Mass vaccination before smallpox introduction or immediately after the first cases was more effective than targeted vaccination in preventing and containing epidemics if there was no prior herd immunity (that is, no prior immunologic protection within the population). The effectiveness of postrelease targeted and mass vaccinations increased if we assumed that there was residual immunity in adults vaccinated before 1972, but the effectiveness of targeted vaccination increased more than that of mass vaccination. Under all scenarios, targeted vaccination prevented more cases per dose of vaccine than did mass vaccination. Although further research with larger-scale structured models is needed, our results suggest that increasing herd immunity, perhaps with a combination of preemptive voluntary vaccination and vaccination of first responders, could enhance the effectiveness of postattack intervention. It could also help targeted vaccination be more competitive with mass vaccination at both preventing and containing a deliberate introduction of smallpox., Recent public debate has focused on choosing a response to an intentional release of smallpox in the United States (1). Routine vaccination against smallpox in the United States was stopped [...]

Objectives. Data from the Tecumseh Community Health Study were used to estimate excess morbidity owing to influenza, and results were compared with estimates made previously using different methodology for an Institute of Medicine report. Methods. Study participants from Tecumseh, Michigan, were classified as infected or noninfected based on laboratory results. The excess numbers of respiratory illnesses, respiratory illness days, and bed and restricted activity days experienced by the infected compared with the noninfected were estimated. Results. The number of excess influenza-related respiratory illnesses was lower than that estimated in the Institute of Medicine report, in which all illnesses of certain characteristics occurring during an influenza season were attributed to influenza. It is now estimated that the US population under 20 years of age experiences a yearly average of 13.8 to 16.0 million influenza-related excess respiratory illnesses; for older individuals, the yearly estimate is 4.1 to 4.4. million excess illnesses. Conclusions. For public health purposes, estimates of excess morbidity as well as of total morbidity associated with influenza should be used in setting health priorities. (Am J Public Health. 1993;83:1712-1716), People under 20 years of age may have a higher risk of influenza infection than older adults. Flu epidemics in Tecumseh, MI, were studied from 1976 to 1981. Households were randomly selected and monitored for respiratory illness, number of sick days and restrictions on activity from illness, and when illness occurred during the year. A person was considered infected if a virus was isolated or had a rise in influenza antibody level. Influenza infection was reported in each year of the study. The most common forms were type A and Type B. For all the years and age groups studied, the highest rate of infection occurred among the youngest age groups (under 20 years of age). The longest duration of illness and restricted activity also was generally among the younger age groups. The average rate of infection was 182 episodes per 1,000 people for all age groups. The excess number of respiratory infection caused by influenza indicates the minimum overall burden of disease. For a cost-benefit analysis, measuring this excess may be valuable for creating public health policy.

Viruses transmitted by Aedes mosquitoes, such as dengue, Zika, and chikungunya, have expanding ranges and seem unabated by current vector control programs. Effective control of these pathogens likely requires integrated approaches. We evaluated dengue management options in an endemic setting that combine novel vector control and vaccination using an agent-based model for Yucata'n, Mexico, fit to 37 y of data. Our intervention models are informed by targeted indoor residual spraying (TIRS) experiments; trial outcomes and World Health Organization (WHO) testing guidance for the only licensed dengue vaccine, CYD-TDV; and preliminary results for in-development vaccines. We evaluated several implementation options, including varying coverage levels; staggered introductions; and a one-time, large-scale vaccination campaign. We found that CYD-TDV and TIRS interfere: while the combination outperforms either alone, performance is lower than estimated from their separate benefits. The conventional model hypothesized for in-development vaccines, however, performs synergistically with TIRS, amplifying effectiveness well beyond their independent impacts. If the preliminary performance by either of the in-development vaccines is upheld, a one-time, large-scale campaign followed by routine vaccination alongside aggressive new vector control could enable short-term elimination, with nearly all cases avoided for a decade despite continuous dengue reintroductions. If elimination is impracticable due to resource limitations, less ambitious implementations of this combination still produce amplified, longer-lasting effectiveness over single-approach interventions. [ABSTRACT FROM AUTHOR]

Background: Norovirus is a leading cause of outbreaks of acute infectious gastroenteritis worldwide, yet its transmissibility within households and associated risk factors remain unknown in developing countries.Methods: Household, demographic, and clinical data were collected from a semi-urban area in south China where an outbreak occurred in the winter of 2014. Using a Bayesian modeling framework, we assessed the transmissibility and potential risk modifiers in both urban and rural households.Results: In urban apartment buildings, the secondary attack rates were 84% (95% credible interval [CI] = 60%, 96%) among households of size two and 29% (95% CI = 9.6%, 53%) in larger households. In the rural village, secondary attack rate estimates were lower than the urban setting, 13% (0.51%, 54%) for households of size two and 7.3% (0.38%, 27%) for larger households. Males were 31% (95% CI = 3%, 50%) less susceptible to the disease than female. Water disinfection with chlorine was estimated to reduce environmental risk of infection by 60% (95% CI = 26%, 82%), and case isolation was estimated to reduce person-to-person transmission by 65% (95% CI = 15%, 93%). Nausea and vomiting were not associated with household transmission.Conclusions: Norovirus is highly contagious within households, in particular in small households in urban communities. Our results suggest that water disinfection and case isolation are associated with reduction of outbreaks in resource-limited communities. [ABSTRACT FROM AUTHOR]

THE REPORT 'CONTAINING PANDEMIC influenza at the source' by I. M. Longini Jr. et al. (12 Aug., p. 1083) was encouraging that an avian pandemic can be contained if proper [...]

We use a data-driven global stochastic epidemic model to analyze the spread of the Zika virus (ZIKV) in the Americas. The model has high spatial and temporal resolution and integrates real-world demographic, human mobility, socioeconomic, temperature, and vector density data. We estimate that the first introduction of ZIKV to Brazil likely occurred between August 2013 and April 2014 (90% credible interval). We provide simulated epidemic profiles of incident ZIKV infections for several countries in the Americas through February 2017. The ZIKV epidemic is characterized by slow growth and high spatial and seasonal heterogeneity, attributable to the dynamics of the mosquito vector and to the characteristics and mobility of the human populations. We project the expected timing and number of pregnancies infected with ZIKV during the first trimester and provide estimates of microcephaly cases assuming different levels of risk as reported in empirical retrospective studies. Our approach represents a modeling effort aimed at understanding the potential magnitude and timing of the ZIKV epidemic and it can be potentially used as a template for the analysis of future mosquito-borne epidemics. [ABSTRACT FROM AUTHOR]

Background: Among the three countries most affected by the Ebola virus disease outbreak in 2014-2015, Guinea presents an unusual spatiotemporal epidemic pattern, with several waves and a long tail in the decay of the epidemic incidence.Methods: Here, we develop a stochastic agent-based model at the level of a single household that integrates detailed data on Guinean demography, hospitals, Ebola treatment units, contact tracing, and safe burial interventions. The microsimulation-based model is used to assess the effect of each control strategy and the probability of elimination of the epidemic according to different intervention scenarios, including ring vaccination with the recombinant vesicular stomatitis virus-vectored vaccine.Results: The numerical results indicate that the dynamics of the Ebola epidemic in Guinea can be quantitatively explained by the timeline of the implemented interventions. In particular, the early availability of Ebola treatment units and the associated isolation of cases and safe burials helped to limit the number of Ebola cases experienced by Guinea. We provide quantitative evidence of a strong negative correlation between the time series of cases and the number of traced contacts. This result is confirmed by the computational model that suggests that contact tracing effort is a key determinant in the control and elimination of the disease. In data-driven microsimulations, we find that tracing at least 5-10 contacts per case is crucial in preventing epidemic resurgence during the epidemic elimination phase. The computational model is used to provide an analysis of the ring vaccination trial highlighting its potential effect on disease elimination.Conclusions: We identify contact tracing as one of the key determinants of the epidemic's behavior in Guinea, and we show that the early availability of Ebola treatment unit beds helped to limit the number of Ebola cases in Guinea. [ABSTRACT FROM AUTHOR]

A Quantitative Approach. RON BROOKMEYER and MITCHELL H. GAIL. Oxford University Press, New York, 1994. xvi, 354 pp., illus. $49.95. Monographs in Epidemiology and Biostatistics, 22. The London Bills of [...]

Background: Vibrio cholerae infections cluster in households. This study's objective was to quantify the relative contribution of direct, within-household exposure (for example, via contamination of household food, water, or surfaces) to endemic cholera transmission. Quantifying the relative contribution of direct exposure is important for planning effective prevention and control measures. Methodology/Principal Findings: Symptom histories and multiple blood and fecal specimens were prospectively collected from household members of hospital-ascertained cholera cases in Bangladesh from 2001–2006. We estimated the probabilities of cholera transmission through 1) direct exposure within the household and 2) contact with community-based sources of infection. The natural history of cholera infection and covariate effects on transmission were considered. Significant direct transmission (p-value<0.0001) occurred among 1414 members of 364 households. Fecal shedding of O1 El Tor Ogawa was associated with a 4.9% (95% confidence interval: 0.9%–22.8%) risk of infection among household contacts through direct exposure during an 11-day infectious period (mean length). The estimated 11-day risk of O1 El Tor Ogawa infection through exposure to community-based sources was 2.5% (0.8%–8.0%). The corresponding estimated risks for O1 El Tor Inaba and O139 infection were 3.7% (0.7%–16.6%) and 8.2% (2.1%–27.1%) through direct exposure, and 3.4% (1.7%–6.7%) and 2.0% (0.5%–7.3%) through community-based exposure. Children under 5 years-old were at elevated risk of infection. Limitations of the study may have led to an underestimation of the true risk of cholera infection. For instance, available covariate data may have incompletely characterized levels of pre-existing immunity to cholera infection. Transmission via direct exposure occurring outside of the household was not considered. Conclusions: Direct exposure contributes substantially to endemic transmission of symptomatic cholera in an urban setting. We provide the first estimate of the transmissibility of endemic cholera within prospectively-followed members of households. The role of direct transmission must be considered when planning cholera control activities. Author Summary: Since John Snow's ground-breaking investigations of the devastating outbreaks in 19th-century London, cholera has been considered the quintessential waterborne human infection, transmitting via fecal contamination of environmental water sources. Recently, renewed interest has been paid to the potential importance of transmission through direct exposure within close-contact groups, such as, via fecal contamination of surfaces, food, or drinking water within households. Significant direct transmission of cholera within close contact groups would represent a new target for innovative prevention and control strategies. We estimated the probability of transmission 1) via direct contact within 364 urban households located in an endemic cholera setting (Dhaka, Bangladesh) and 2) via exposure to sources located outside of these households. In this setting we estimated a 4 to 8 percent probability of becoming infected with cholera via direct exposure within households in this setting versus a 2 to 3 percent likelihood of infection due to exposure to external sources over a comparable time period. Our results demonstrate that direct (within-household) transmission is a significant component of endemic cholera transmission, suggesting that biomedical and behavioral-modification interventions specifically targeting this mode of transmission could substantially reduce the cholera burden in this type of setting. [ABSTRACT FROM AUTHOR]