Estimating the epidemic reproduction number from temporally aggregated incidence data: A statistical modelling approach and software tool.

The time-varying reproduction number (Rt) is an important measure of epidemic transmissibility that directly informs policy decisions and the optimisation of control measures. EpiEstim is a widely used opensource software tool that uses case incidence and the serial interval (SI, time between symptoms in a case and their infector) to estimate Rt in real-time. The incidence and the SI distribution must be provided at the same temporal resolution, which can limit the applicability of EpiEstim and other similar methods, e.g. for contexts where the time window of incidence reporting is longer than the mean SI. In the EpiEstim R package, we implement an expectation-maximisation algorithm to reconstruct daily incidence from temporally aggregated data, from which Rt can then be estimated. We assess the validity of our method using an extensive simulation study and apply it to COVID-19 and influenza data. For all datasets, the influence of intra-weekly variability in reported data was mitigated by using aggregated weekly data. Rt estimated on weekly sliding windows using incidence reconstructed from weekly data was strongly correlated with estimates from the original daily data. The simulation study revealed that Rt was well estimated in all scenarios and regardless of the temporal aggregation of the data. In the presence of weekend effects, Rt estimates from reconstructed data were more successful at recovering the true value of Rt than those obtained from reported daily data. These results show that this novel method allows Rt to be successfully recovered from aggregated data using a simple approach with very few data requirements. Additionally, by removing administrative noise when daily incidence data are reconstructed, the accuracy of Rt estimates can be improved.

Transmission dynamics of lyssavirus in Myotis myotis: mechanistic modelling study based on longitudinal seroprevalence data.

We investigated the transmission dynamics of lyssavirus in Myotis myotis and Myotis blythii, using serological, virological, demographic and ecological data collected between 2015 and 2022 from two maternity colonies in northern Italian churches. Despite no lyssavirus detection in 556 bats sampled over 11 events by reverse transcription-polymerase chain reaction (RT-PCR), 36.3% of 837 bats sampled over 27 events showed neutralizing antibodies to European bat lyssavirus 1, with a significant increase in summers. By fitting sets of mechanistic models to seroprevalence data, we investigated factors that influenced lyssavirus transmission within and between years. Five models were selected as a group of final models: in one model, a proportion of exposed bats (median model estimate: 5.8%) became infectious and died while the other exposed bats recovered with immunity without becoming infectious; in the other four models, all exposed bats became infectious and recovered with immunity. The final models supported that the two colonies experienced seasonal outbreaks driven by: (i) immunity loss particularly during hibernation, (ii) density-dependent transmission, and (iii) a high transmission rate after synchronous birthing. These findings highlight the importance of understanding ecological factors, including colony size and synchronous birthing timing, and potential infection heterogeneities to enable more robust assessments of lyssavirus spillover risk.

Spatial and temporal invasion dynamics of the 2014-2017 Zika and chikungunya epidemics in Colombia.

Zika virus (ZIKV) and chikungunya virus (CHIKV) were recently introduced into the Americas resulting in significant disease burdens. Understanding their spatial and temporal dynamics at the subnational level is key to informing surveillance and preparedness for future epidemics. We analyzed anonymized line list data on approximately 105,000 Zika virus disease and 412,000 chikungunya fever suspected and laboratory-confirmed cases during the 2014-2017 epidemics. We first determined the week of invasion in each city. Out of 1,122, 288 cities met criteria for epidemic invasion by ZIKV and 338 cities by CHIKV. We analyzed risk factors for invasion using linear and logistic regression models. We also estimated that the geographic origin of both epidemics was located in Barranquilla, north Colombia. We assessed the spatial and temporal invasion dynamics of both viruses to analyze transmission between cities using a suite of (i) gravity models, (ii) Stouffer's rank models, and (iii) radiation models with two types of distance metrics, geographic distance and travel time between cities. Invasion risk was best captured by a gravity model when accounting for geographic distance and intermediate levels of density dependence; Stouffer's rank model with geographic distance performed similarly well. Although a few long-distance invasion events occurred at the beginning of the epidemics, an estimated distance power of 1.7 (95% CrI: 1.5-2.0) from the gravity models suggests that spatial spread was primarily driven by short-distance transmission. Similarities between the epidemics were highlighted by jointly fitted models, which were preferred over individual models when the transmission intensity was allowed to vary across arboviruses. However, ZIKV spread considerably faster than CHIKV.

Understanding the incidence and timing of rabies cases in domestic animals and wildlife in south-east Tanzania in the presence of widespread domestic dog vaccination campaigns.

The "Zero by 30" strategic plan aims to eliminate human deaths from dog-mediated rabies by 2030 and domestic dog vaccination is a vital component of this strategic plan. In areas where domestic dog vaccination has been implemented, it is important to assess the impact of this intervention. Additionally, understanding temporal and seasonal trends in the incidence of animal rabies cases may assist in optimizing such interventions. Data on the incidence of probable rabies cases in domestic and wild animals were collected between January 2011 and December 2018 in thirteen districts of south-east Tanzania where jackals comprise over 40% of reported rabies cases. Vaccination coverage was estimated over this period, as five domestic dog vaccination campaigns took place in all thirteen districts between 2011 and 2016. Negative binomial generalized linear models were used to explore the impact of domestic dog vaccination on the annual incidence of animal rabies cases, whilst generalized additive models were used to investigate the presence of temporal and/or seasonal trends. Increases in domestic dog vaccination coverage were significantly associated with a decreased incidence of rabies cases in both domestic dogs and jackals. A 35% increase in vaccination coverage was associated with a reduction in the incidence of probable dog rabies cases of between 78.0 and 85.5% (95% confidence intervals ranged from 61.2 to 92.2%) and a reduction in the incidence of probable jackal rabies cases of between 75.3 and 91.2% (95% confidence intervals ranged from 53.0 to 96.1%). A statistically significant common seasonality was identified in the monthly incidence of probable rabies cases in both domestic dogs and jackals with the highest incidence from February to August and lowest incidence from September to January. These results align with evidence supporting the use of domestic dog vaccination as part of control strategies aimed at reducing animal rabies cases in both domestic dogs and jackals in this region. The presence of a common seasonal trend requires further investigation but may have implications for the timing of future vaccination campaigns.

Spatiotemporal variations in exposure: Chagas disease in Colombia as a case study.

Age-stratified serosurvey data are often used to understand spatiotemporal trends in disease incidence and exposure through estimating the Force-of-Infection (FoI). Typically, median or mean FoI estimates are used as the response variable in predictive models, often overlooking the uncertainty in estimated FoI values when fitting models and evaluating their predictive ability. To assess how this uncertainty impact predictions, we compared three approaches with three levels of uncertainty integration. We propose a performance indicator to assess how predictions reflect initial uncertainty.In Colombia, 76 serosurveys (1980-2014) conducted at municipality level provided age-stratified Chagas disease prevalence data. The yearly FoI was estimated at the serosurvey level using a time-varying catalytic model. Environmental, demographic and entomological predictors were used to fit and predict the FoI at municipality level from 1980 to 2010 across Colombia.A stratified bootstrap method was used to fit the models without temporal autocorrelation at the serosurvey level. The predictive ability of each model was evaluated to select the best-fit models within urban, rural and (Amerindian) indigenous settings. Model averaging, with the 10 best-fit models identified, was used to generate predictions.Our analysis shows a risk of overconfidence in model predictions when median estimates of FoI alone are used to fit and evaluate models, failing to account for uncertainty in FoI estimates. Our proposed methodology fully propagates uncertainty in the estimated FoI onto the generated predictions, providing realistic assessments of both central tendency and current uncertainty surrounding exposure to Chagas disease.

Using syndromic measures of mortality to capture the dynamics of COVID-19 in Java, Indonesia, in the context of vaccination rollout.

BACKGROUND: As in many countries, quantifying COVID-19 spread in Indonesia remains challenging due to testing limitations. In Java, non-pharmaceutical interventions (NPIs) were implemented throughout 2020. However, as a vaccination campaign launches, cases and deaths are rising across the island. METHODS: We used modelling to explore the extent to which data on burials in Jakarta using strict COVID-19 protocols (C19P) provide additional insight into the transmissibility of the disease, epidemic trajectory, and the impact of NPIs. We assess how implementation of NPIs in early 2021 will shape the epidemic during the period of likely vaccine rollout. RESULTS: C19P burial data in Jakarta suggest a death toll approximately 3.3 times higher than reported. Transmission estimates using these data suggest earlier, larger, and more sustained impact of NPIs. Measures to reduce sub-national spread, particularly during Ramadan, substantially mitigated spread to more vulnerable rural areas. Given current trajectory, daily cases and deaths are likely to increase in most regions as the vaccine is rolled out. Transmission may peak in early 2021 in Jakarta if current levels of control are maintained. However, relaxation of control measures is likely to lead to a subsequent resurgence in the absence of an effective vaccination campaign. CONCLUSIONS: Syndromic measures of mortality provide a more complete picture of COVID-19 severity upon which to base decision-making. The high potential impact of the vaccine in Java is attributable to reductions in transmission to date and dependent on these being maintained. Increases in control in the relatively short-term will likely yield large, synergistic increases in vaccine impact.

The role of rapid diagnostics in managing Ebola epidemics.

Ebola emerged in West Africa around December 2013 and swept through Guinea, Sierra Leone and Liberia, giving rise to 27,748 confirmed, probable and suspected cases reported by 29 July 2015. Case diagnoses during the epidemic have relied on polymerase chain reaction-based tests. Owing to limited laboratory capacity and local transport infrastructure, the delays from sample collection to test results being available have often been 2 days or more. Point-of-care rapid diagnostic tests offer the potential to substantially reduce these delays. We review Ebola rapid diagnostic tests approved by the World Health Organization and those currently in development. Such rapid diagnostic tests could allow early triaging of patients, thereby reducing the potential for nosocomial transmission. In addition, despite the lower test accuracy, rapid diagnostic test-based diagnosis may be beneficial in some contexts because of the reduced time spent by uninfected individuals in health-care settings where they may be at increased risk of infection; this also frees up hospital beds. We use mathematical modelling to explore the potential benefits of diagnostic testing strategies involving rapid diagnostic tests alone and in combination with polymerase chain reaction testing. Our analysis indicates that the use of rapid diagnostic tests with sensitivity and specificity comparable with those currently under development always enhances control, whether evaluated at a health-care-unit or population level. If such tests had been available throughout the recent epidemic, we estimate, for Sierra Leone, that their use in combination with confirmatory polymerase chain-reaction testing might have reduced the scale of the epidemic by over a third.

Case Fatality Ratio Estimates for the 2013-2016 West African Ebola Epidemic: Application of Boosted Regression Trees for Imputation.

BACKGROUND: The 2013-2016 West African Ebola epidemic has been the largest to date with >11 000 deaths in the affected countries. The data collected have provided more insight into the case fatality ratio (CFR) and how it varies with age and other characteristics. However, the accuracy and precision of the naive CFR remain limited because 44% of survival outcomes were unreported. METHODS: Using a boosted regression tree model, we imputed survival outcomes (ie, survival or death) when unreported, corrected for model imperfection to estimate the CFR without imputation, with imputation, and adjusted with imputation. The method allowed us to further identify and explore relevant clinical and demographic predictors of the CFR. RESULTS: The out-of-sample performance (95% confidence interval [CI]) of our model was good: sensitivity, 69.7% (52.5-75.6%); specificity, 69.8% (54.1-75.6%); percentage correctly classified, 69.9% (53.7-75.5%); and area under the receiver operating characteristic curve, 76.0% (56.8-82.1%). The adjusted CFR estimates (95% CI) for the 2013-2016 West African epidemic were 82.8% (45.6-85.6%) overall and 89.1% (40.8-91.6%), 65.6% (61.3-69.6%), and 79.2% (45.4-84.1%) for Sierra Leone, Guinea, and Liberia, respectively. We found that district, hospitalisation status, age, case classification, and quarter (date of case reporting aggregated at three-month intervals) explained 93.6% of the variance in the naive CFR. CONCLUSIONS: The adjusted CFR estimates improved the naive CFR estimates obtained without imputation and were more representative. Used in conjunction with other resources, adjusted estimates will inform public health contingency planning for future Ebola epidemics, and help better allocate resources and evaluate the effectiveness of future inventions.

Response to COVID-19 in South Korea and implications for lifting stringent interventions.

BACKGROUND: After experiencing a sharp growth in COVID-19 cases early in the pandemic, South Korea rapidly controlled transmission while implementing less stringent national social distancing measures than countries in Europe and the USA. This has led to substantial interest in their "test, trace, isolate" strategy. However, it is important to understand the epidemiological peculiarities of South Korea's outbreak and characterise their response before attempting to emulate these measures elsewhere. METHODS: We systematically extracted numbers of suspected cases tested, PCR-confirmed cases, deaths, isolated confirmed cases, and numbers of confirmed cases with an identified epidemiological link from publicly available data. We estimated the time-varying reproduction number, Rt, using an established Bayesian framework, and reviewed the package of interventions implemented by South Korea using our extracted data, plus published literature and government sources. RESULTS: We estimated that after the initial rapid growth in cases, Rt dropped below one in early April before increasing to a maximum of 1.94 (95%CrI, 1.64-2.27) in May following outbreaks in Seoul Metropolitan Region. By mid-June, Rt was back below one where it remained until the end of our study (July 13th). Despite less stringent "lockdown" measures, strong social distancing measures were implemented in high-incidence areas and studies measured a considerable national decrease in movement in late February. Testing the capacity was swiftly increased, and protocols were in place to isolate suspected and confirmed cases quickly; however, we could not estimate the delay to isolation using our data. Accounting for just 10% of cases, individual case-based contact tracing picked up a relatively minor proportion of total cases, with cluster investigations accounting for 66%. CONCLUSIONS: Whilst early adoption of testing and contact tracing is likely to be important for South Korea's successful outbreak control, other factors including regional implementation of strong social distancing measures likely also contributed. The high volume of testing and the low number of deaths suggest that South Korea experienced a small epidemic relative to other countries. Caution is needed in attempting to replicate the South Korean response in populations with larger more geographically widespread epidemics where finding, testing, and isolating cases that are linked to clusters may be more difficult.

Sub- or supercritical transmissibilities in a finite disease outbreak: Symmetry in outbreak properties of a disease conditioned on extinction.

This work is concerned with the transmissibility of a disease, on observation of an outbreak of limited size. When such an outbreak occurs, an accurate estimate of the transmissibility of the responsible pathogen is essential for an appropriate response to future outbreaks. Transmissibility is usually characterised in terms of the reproduction number, R, which is the mean number of new cases of infection produced by a single infectious individual. A subcritical reproduction number (R < 1) guarantees that an outbreak will eventually die out of its own accord. By contrast, a supercritical reproduction number (R > 1) does not guarantee spread of the disease, since even with appreciable transmissibility, an outbreak may become extinct due to stochastic effects associated with a small number of infected individuals. Once the number of infectious individuals is conditioned on extinction, we show that an exact symmetry of the underlying theory ensures two distinct values of R, one larger than unity, the other smaller than unity, for which all outbreak properties are identical, with no signature of difference. Therefore a disease with a subcritical R, or its supercritical counterpart, when conditioned on extinction, have, for a given outbreak, identical individual likelihoods. In the full likelihood, this symmetry is lost, since the individual likelihood for a subcritical R is weighted by an extinction probability of unity, but the individual likelihood of a supercritical R is weighted by a sub-unity extinction probability. However, the inference can still benefit from the underlying symmetry, since it yields a mapping of all supercritical reproduction numbers onto the subcritical domain (R < 1), thereby speeding up evaluation of the likelihood profile. The symmetry holds in the standard situation, where the distribution of secondary cases is Poisson, as well as where this distribution has a negative binomial form and super-spreading can occur.

A graph-based evidence synthesis approach to detecting outbreak clusters: An application to dog rabies.

Early assessment of infectious disease outbreaks is key to implementing timely and effective control measures. In particular, rapidly recognising whether infected individuals stem from a single outbreak sustained by local transmission, or from repeated introductions, is crucial to adopt effective interventions. In this study, we introduce a new framework for combining several data streams, e.g. temporal, spatial and genetic data, to identify clusters of related cases of an infectious disease. Our method explicitly accounts for underreporting, and allows incorporating preexisting information about the disease, such as its serial interval, spatial kernel, and mutation rate. We define, for each data stream, a graph connecting all cases, with edges weighted by the corresponding pairwise distance between cases. Each graph is then pruned by removing distances greater than a given cutoff, defined based on preexisting information on the disease and assumptions on the reporting rate. The pruned graphs corresponding to different data streams are then merged by intersection to combine all data types; connected components define clusters of cases related for all types of data. Estimates of the reproduction number (the average number of secondary cases infected by an infectious individual in a large population), and the rate of importation of the disease into the population, are also derived. We test our approach on simulated data and illustrate it using data on dog rabies in Central African Republic. We show that the outbreak clusters identified using our method are consistent with structures previously identified by more complex, computationally intensive approaches.

Unraveling the drivers of MERS-CoV transmission.

With more than 1,700 laboratory-confirmed infections, Middle East respiratory syndrome coronavirus (MERS-CoV) remains a significant threat for public health. However, the lack of detailed data on modes of transmission from the animal reservoir and between humans means that the drivers of MERS-CoV epidemics remain poorly characterized. Here, we develop a statistical framework to provide a comprehensive analysis of the transmission patterns underlying the 681 MERS-CoV cases detected in the Kingdom of Saudi Arabia (KSA) between January 2013 and July 2014. We assess how infections from the animal reservoir, the different levels of mixing, and heterogeneities in transmission have contributed to the buildup of MERS-CoV epidemics in KSA. We estimate that 12% [95% credible interval (CI): 9%, 15%] of cases were infected from the reservoir, the rest via human-to-human transmission in clusters (60%; CI: 57%, 63%), within (23%; CI: 20%, 27%), or between (5%; CI: 2%, 8%) regions. The reproduction number at the start of a cluster was 0.45 (CI: 0.33, 0.58) on average, but with large SD (0.53; CI: 0.35, 0.78). It was >1 in 12% (CI: 6%, 18%) of clusters but fell by approximately one-half (47% CI: 34%, 63%) its original value after 10 cases on average. The ongoing exposure of humans to MERS-CoV from the reservoir is of major concern, given the continued risk of substantial outbreaks in health care systems. The approach we present allows the study of infectious disease transmission when data linking cases to each other remain limited and uncertain.

Complementary Paths to Chagas Disease Elimination: The Impact of Combining Vector Control With Etiological Treatment.

Background: The World Health Organization's 2020 goals for Chagas disease are (1) interrupting vector-borne intradomiciliary transmission and (2) having all infected people under care in endemic countries. Insecticide spraying has proved efficacious for reaching the first goal, but active transmission remains in several regions. For the second, treatment has mostly been restricted to recently infected patients, who comprise only a small proportion of all infected individuals. Methods: We extended our previous dynamic transmission model to simulate a domestic Chagas disease transmission cycle and examined the effects of both vector control and etiological treatment on achieving the operational criterion proposed by the Pan American Health Organization for intradomiciliary, vectorial transmission interruption (ie, <2% seroprevalence in children <5 years of age). Results: Depending on endemicity, an antivectorial intervention that decreases vector density by 90% annually would achieve the transmission interruption criterion in 2-3 years (low endemicity) to >30 years (high endemicity). When this strategy is combined with annual etiological treatment in 10% of the infected human population, the seroprevalence criterion would be achieved, respectively, in 1 and 11 years. Conclusions: Combining highly effective vector control with etiological (trypanocidal) treatment in humans would substantially reduce time to transmission interruption as well as infection incidence and prevalence. However, the success of vector control may depend on prevailing vector species. It will be crucial to improve the coverage of screening programs, the performance of diagnostic tests, the proportion of people treated, and the efficacy of trypanocidal drugs. While screening and access can be incremented as part of strengthening the health systems response, improving diagnostics performance and drug efficacy will require further research.

Revealing the Micro-scale Signature of Endemic Zoonotic Disease Transmission in an African Urban Setting.

The development of novel approaches that combine epidemiological and genomic data provides new opportunities to reveal the spatiotemporal dynamics of infectious diseases and determine the processes responsible for their spread and maintenance. Taking advantage of detailed epidemiological time series and viral sequence data from more than 20 years reported by the National Reference Centre for Rabies of Bangui, the capital city of Central African Republic, we used a combination of mathematical modeling and phylogenetic analysis to determine the spatiotemporal dynamics of rabies in domestic dogs as well as the frequency of extinction and introduction events in an African city. We show that although dog rabies virus (RABV) appears to be endemic in Bangui, its epidemiology is in fact shaped by the regular extinction of local chains of transmission coupled with the introduction of new lineages, generating successive waves of spread. Notably, the effective reproduction number during each wave was rarely above the critical value of 1, such that rabies is not self-sustaining in Bangui. In turn, this suggests that rabies at local geographic scales is driven by human-mediated dispersal of RABV among sparsely connected peri-urban and rural areas as opposed to dispersion in a relatively large homogenous urban dog population. This combined epidemiological and genomic approach enables development of a comprehensive framework for understanding disease persistence and informing control measures, indicating that control measures are probably best targeted towards areas neighbouring the city that appear as the source of frequent incursions seeding outbreaks in Bangui.

Ebola virus disease in West Africa--the first 9 months of the epidemic and forward projections.

BACKGROUND: On March 23, 2014, the World Health Organization (WHO) was notified of an outbreak of Ebola virus disease (EVD) in Guinea. On August 8, the WHO declared the epidemic to be a "public health emergency of international concern." METHODS: By September 14, 2014, a total of 4507 probable and confirmed cases, including 2296 deaths from EVD (Zaire species) had been reported from five countries in West Africa--Guinea, Liberia, Nigeria, Senegal, and Sierra Leone. We analyzed a detailed subset of data on 3343 confirmed and 667 probable Ebola cases collected in Guinea, Liberia, Nigeria, and Sierra Leone as of September 14. RESULTS: The majority of patients are 15 to 44 years of age (49.9% male), and we estimate that the case fatality rate is 70.8% (95% confidence interval [CI], 69 to 73) among persons with known clinical outcome of infection. The course of infection, including signs and symptoms, incubation period (11.4 days), and serial interval (15.3 days), is similar to that reported in previous outbreaks of EVD. On the basis of the initial periods of exponential growth, the estimated basic reproduction numbers (R0 ) are 1.71 (95% CI, 1.44 to 2.01) for Guinea, 1.83 (95% CI, 1.72 to 1.94) for Liberia, and 2.02 (95% CI, 1.79 to 2.26) for Sierra Leone. The estimated current reproduction numbers (R) are 1.81 (95% CI, 1.60 to 2.03) for Guinea, 1.51 (95% CI, 1.41 to 1.60) for Liberia, and 1.38 (95% CI, 1.27 to 1.51) for Sierra Leone; the corresponding doubling times are 15.7 days (95% CI, 12.9 to 20.3) for Guinea, 23.6 days (95% CI, 20.2 to 28.2) for Liberia, and 30.2 days (95% CI, 23.6 to 42.3) for Sierra Leone. Assuming no change in the control measures for this epidemic, by November 2, 2014, the cumulative reported numbers of confirmed and probable cases are predicted to be 5740 in Guinea, 9890 in Liberia, and 5000 in Sierra Leone, exceeding 20,000 in total. CONCLUSIONS: These data indicate that without drastic improvements in control measures, the numbers of cases of and deaths from EVD are expected to continue increasing from hundreds to thousands per week in the coming months.

Exposure Patterns Driving Ebola Transmission in West Africa: A Retrospective Observational Study.

BACKGROUND: The ongoing West African Ebola epidemic began in December 2013 in Guinea, probably from a single zoonotic introduction. As a result of ineffective initial control efforts, an Ebola outbreak of unprecedented scale emerged. As of 4 May 2015, it had resulted in more than 19,000 probable and confirmed Ebola cases, mainly in Guinea (3,529), Liberia (5,343), and Sierra Leone (10,746). Here, we present analyses of data collected during the outbreak identifying drivers of transmission and highlighting areas where control could be improved. METHODS AND FINDINGS: Over 19,000 confirmed and probable Ebola cases were reported in West Africa by 4 May 2015. Individuals with confirmed or probable Ebola ("cases") were asked if they had exposure to other potential Ebola cases ("potential source contacts") in a funeral or non-funeral context prior to becoming ill. We performed retrospective analyses of a case line-list, collated from national databases of case investigation forms that have been reported to WHO. These analyses were initially performed to assist WHO's response during the epidemic, and have been updated for publication. We analysed data from 3,529 cases in Guinea, 5,343 in Liberia, and 10,746 in Sierra Leone; exposures were reported by 33% of cases. The proportion of cases reporting a funeral exposure decreased over time. We found a positive correlation (r = 0.35, p < 0.001) between this proportion in a given district for a given month and the within-district transmission intensity, quantified by the estimated reproduction number (R). We also found a negative correlation (r = -0.37, p < 0.001) between R and the district proportion of hospitalised cases admitted within ≤4 days of symptom onset. These two proportions were not correlated, suggesting that reduced funeral attendance and faster hospitalisation independently influenced local transmission intensity. We were able to identify 14% of potential source contacts as cases in the case line-list. Linking cases to the contacts who potentially infected them provided information on the transmission network. This revealed a high degree of heterogeneity in inferred transmissions, with only 20% of cases accounting for at least 73% of new infections, a phenomenon often called super-spreading. Multivariable regression models allowed us to identify predictors of being named as a potential source contact. These were similar for funeral and non-funeral contacts: severe symptoms, death, non-hospitalisation, older age, and travelling prior to symptom onset. Non-funeral exposures were strongly peaked around the death of the contact. There was evidence that hospitalisation reduced but did not eliminate onward exposures. We found that Ebola treatment units were better than other health care facilities at preventing exposure from hospitalised and deceased individuals. The principal limitation of our analysis is limited data quality, with cases not being entered into the database, cases not reporting exposures, or data being entered incorrectly (especially dates, and possible misclassifications). CONCLUSIONS: Achieving elimination of Ebola is challenging, partly because of super-spreading. Safe funeral practices and fast hospitalisation contributed to the containment of this Ebola epidemic. Continued real-time data capture, reporting, and analysis are vital to track transmission patterns, inform resource deployment, and thus hasten and maintain elimination of the virus from the human population.

Temporal variations in international air travel: implications for modelling the spread of infectious diseases.

BACKGROUND: The international flight network creates multiple routes by which pathogens can quickly spread across the globe. In the early stages of infectious disease outbreaks, analyses using flight passenger data to identify countries at risk of importing the pathogen are common and can help inform disease control efforts. A challenge faced in this modelling is that the latest aviation statistics (referred to as contemporary data) are typically not immediately available. Therefore, flight patterns from a previous year are often used (referred to as historical data). We explored the suitability of historical data for predicting the spatial spread of emerging epidemics. METHODS: We analysed monthly flight passenger data from the International Air Transport Association to assess how baseline air travel patterns were affected by outbreaks of Middle East respiratory syndrome (MERS), Zika and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) over the past decade. We then used a stochastic discrete time susceptible-exposed-infected-recovered (SEIR) metapopulation model to simulate the global spread of different pathogens, comparing how epidemic dynamics differed in simulations based on historical and contemporary data. RESULTS: We observed local, short-term disruptions to air travel from South Korea and Brazil for the MERS and Zika outbreaks we studied, whereas global and longer-term flight disruptions occurred during the SARS-CoV-2 pandemic. For outbreak events that were accompanied by local, small and short-term changes in air travel, epidemic models using historical flight data gave similar projections of the timing and locations of disease spread as when using contemporary flight data. However, historical data were less reliable to model the spread of an atypical outbreak such as SARS-CoV-2, in which there were durable and extensive levels of global travel disruption. CONCLUSION: The use of historical flight data as a proxy in epidemic models is an acceptable practice, except in rare, large epidemics that lead to substantial disruptions to international travel.