An inaugural forum on epidemiological modeling for public health stakeholders in Arizona.

Epidemiological models-which help us understand and forecast the spread of infectious disease-can be valuable tools for public health. However, barriers exist that can make it difficult to employ epidemiological models routinely within the repertoire of public health planning. These barriers include technical challenges associated with constructing the models, challenges in obtaining appropriate data for model parameterization, and problems with clear communication of modeling outputs and uncertainty. To learn about the unique barriers and opportunities within the state of Arizona, we gathered a diverse set of 48 public health stakeholders for a day-and-a-half forum. Our research group was motivated specifically by our work building software for public health-relevant modeling and by our earnest desire to collaborate closely with stakeholders to ensure that our software tools are practical and useful in the face of evolving public health needs. Here we outline the planning and structure of the forum, and we highlight as a case study some of the lessons learned from breakout discussions. While unique barriers exist for implementing modeling for public health, there is also keen interest in doing so across diverse sectors of State and Local government, although issues of equal and fair access to modeling knowledge and technologies remain key issues for future development. We found this forum to be useful for building relationships and informing our software development, and we plan to continue such meetings annually to create a continual feedback loop between academic molders and public health practitioners.

A simulation-based approach for estimating the time-dependent reproduction number from temporally aggregated disease incidence time series data.

Tracking pathogen transmissibility during infectious disease outbreaks is essential for assessing the effectiveness of public health measures and planning future control strategies. A key measure of transmissibility is the time-dependent reproduction number, which has been estimated in real-time during outbreaks of a range of pathogens from disease incidence time series data. While commonly used approaches for estimating the time-dependent reproduction number can be reliable when disease incidence is recorded frequently, such incidence data are often aggregated temporally (for example, numbers of cases may be reported weekly rather than daily). As we show, commonly used methods for estimating transmissibility can be unreliable when the timescale of transmission is shorter than the timescale of data recording. To address this, here we develop a simulation-based approach involving Approximate Bayesian Computation for estimating the time-dependent reproduction number from temporally aggregated disease incidence time series data. We first use a simulated dataset representative of a situation in which daily disease incidence data are unavailable and only weekly summary values are reported, demonstrating that our method provides accurate estimates of the time-dependent reproduction number under such circumstances. We then apply our method to two outbreak datasets consisting of weekly influenza case numbers in 2019-20 and 2022-23 in Wales (in the United Kingdom). Our simple-to-use approach will allow accurate estimates of time-dependent reproduction numbers to be obtained from temporally aggregated data during future infectious disease outbreaks.

Looking under the lamp-post: quantifying the performance of contact tracing in the United States during the SARS-CoV-2 pandemic.

Contact tracing forms a crucial part of the public-health toolbox in mitigating and understanding emergent pathogens and nascent disease outbreaks. Contact tracing in the United States was conducted during the pre-Omicron phase of the ongoing COVID-19 pandemic. This tracing relied on voluntary reporting and responses, often using rapid antigen tests due to lack of accessibility to PCR tests. These limitations, combined with SARS-CoV-2's propensity for asymptomatic transmission, raise the question "how reliable was contact tracing for COVID-19 in the United States"? We answered this question using a Markov model to examine the efficiency with which transmission could be detected based on the design and response rates of contact tracing studies in the United States. Our results suggest that contact tracing protocols in the U.S. are unlikely to have identified more than 1.65% (95% uncertainty interval: 1.62-1.68%) of transmission events with PCR testing and 1.00% (95% uncertainty interval 0.98-1.02%) with rapid antigen testing. When considering a more robust contact tracing scenario, based on compliance rates in East Asia with PCR testing, this increases to 62.7% (95% uncertainty interval: 62.6-62.8%). We did not assume presence of asymptomatic transmission or superspreading, making our estimates upper bounds on the actual percentages traced. These findings highlight the limitations in interpretability for studies of SARS-CoV-2 disease spread based on U.S. contact tracing and underscore the vulnerability of the population to future disease outbreaks, for SARS-CoV-2 and other pathogens.

Case-control study of behavioural and societal risk factors for sporadic SARS-CoV-2 infections, Germany, 2020-2021 (CoViRiS study).

During the COVID-19 pandemic in Germany, a variety of societal activities were restricted to minimize direct personal interactions and, consequently, reduce SARS-CoV-2 transmission. The aim of the CoViRiS study was to investigate whether certain behaviours and societal factors were associated with the risk of sporadic symptomatic SARS-CoV-2 infections. Adult COVID-19 cases and frequency-matched population controls were interviewed by telephone regarding activities that involved contact with other people during the 10 days before illness onset (cases) or before the interview (controls). Associations between activities and symptomatic SARS-CoV-2 infection were analysed using logistic regression models adjusted for potential confounding variables. Data of 859 cases and 1 971 controls were available for analysis. The risk of symptomatic SARS-CoV-2 infection was lower for individuals who worked from home (adjusted odds ratio (aOR) 0.5; 95% confidence interval (CI) 0.3-0.6). Working in a health care setting was associated with a higher risk (aOR: 1.5; 95% CI: 1.1-2.1) as were private indoor contacts, personal contacts that involved shaking hands or hugging, and overnight travelling within Germany. Our results are in line with some of the public health recommendations aimed at reducing interpersonal contacts during the COVID-19 pandemic.

High prevalence of asymptomatic malaria in Forest Guinea: Results from a rapid community survey.

Malaria is endemic in Guinea; however, the extent and role in transmission of asymptomatic malaria are not well understood. In May 2023, we conducted a rapid community survey to determine Plasmodium falciparum (P. falciparum) prevalence among asymptomatic individuals in Middle Guinea (Prefecture Dalaba) and Forest Guinea (Prefecture Guéckédou). In Dalaba, 6 of 239 (2.1%, confidence interval (CI) 0.9-4.8%) individuals tested positive for P. falciparum by a rapid diagnostic test (RDT), while in Guéckédou, 147 of 235 (60.9%, CI 54.5-66.9%) participants tested positive. Asymptomatic malaria needs to be considered more strongly as a driver of transmission when designing control strategies, especially in Forest Guinea and potentially other hyper-endemic settings.

Exact calculation of end-of-outbreak probabilities using contact tracing data.

A key challenge for public health policymakers is determining when an infectious disease outbreak has finished. Following a period without cases, an estimate of the probability that no further cases will occur in future (the end-of-outbreak probability) can be used to inform whether or not to declare an outbreak over. An existing quantitative approach (the Nishiura method), based on a branching process transmission model, allows the end-of-outbreak probability to be approximated from disease incidence time series, the offspring distribution and the serial interval distribution. Here, we show how the end-of-outbreak probability under the same transmission model can be calculated exactly if data describing who-infected-whom (the transmission tree) are also available (e.g. from contact tracing studies). In that scenario, our novel approach (the traced transmission method) is straightforward to use. We demonstrate this by applying the method to data from previous outbreaks of Ebola virus disease and Nipah virus infection. For both outbreaks, the traced transmission method would have determined that the outbreak was over earlier than the Nishiura method. This highlights that collection of contact tracing data and application of the traced transmission method may allow stringent control interventions to be relaxed quickly at the end of an outbreak, with only a limited risk of outbreak resurgence.

Mapping the stability of febrile illness hotspots in Punjab from 2012 to 2019- a spatial clustering and regression analysis.

INTRODUCTION: Febrile illnesses (FI) represent a typical spectrum of diseases in low-resource settings, either in isolation or with other common symptoms. They contribute substantially to morbidity and mortality in India. The primary objective was to study the burden of FI based on Integrated Disease Surveillance Programme (IDSP) data in Punjab, analyze geospatial and temporal trends and patterns, and identify the potential hotspots for effective intervention. METHODS: A retrospective ecological study used the district-level IDSP reports between 2012 and 2019. Diseases responsible for FI on a large scale, like Dengue, Chikungunya, Malaria (Plasmodium Falciparum, P. Vivax), Enteric fever, and Pyrexia of Unknown Origin (PUO), were included in the analysis. The digital map of Punjab was obtained from GitHub. Spatial autocorrelation and cluster analysis were done using Moran's I and Getis-Ord G* to determine hotspots of FI using the incidence and crude disease numbers reported under IDSP. Further, negative binomial regression was used to determine the association between Spatio-temporal and population variables per the census 2011. Stable hotspots were depicted using heat maps generated from district-wise yearly data. RESULTS: PUO was the highest reported FI. We observed a rising trend in the incidence of Dengue, Chikungunya, and Enteric fever, which depicted occasional spikes during the study period. FI expressed significant inter-district variations and clustering during the start of the study period, with more dispersion in the latter part of the study period. P.Vivax malaria depicted stable hotspots in southern districts of Punjab. In contrast, P. Falciparum malaria, Chikungunya, and PUO expressed no spatial patterns. Enteric Fever incidence was high in central and northeastern districts but depicted no stable spatial patterns. Certain districts were common incidence hotspots for multiple diseases. The number of cases in each district has shown over-dispersion for each disease and has little dependence on population, gender, or residence as per regression analysis. CONCLUSIONS: The study demonstrates that information obtained through IDSP can describe the spatial epidemiology of FI at crude spatial scales and drive concerted efforts against FI by identifying actionable points.

Travel-related giardiasis: incidence and time trends for various destination countries.

BACKGROUND: Giardiasis is a common gastrointestinal illness in travellers. Data on the actual giardiasis risk of travellers to different travel destinations are scarce. We aim to estimate the risk of giardiasis in travellers from Germany by destination country and region. METHODS: We analysed travel-related giardiasis cases, their countries and regions of exposure and the age and sex distribution of cases reported in 2014-19 in Germany. We defined a travel-related giardiasis case as a laboratory-confirmed (i.e. positive microscopy, antigen test or nucleic acid test) symptomatic individual with outbound travel abroad within 3-25 days before symptom onset. Based on the number of reported cases per exposure country and UNWTO travel data for Germany, we calculated the number of travel-related giardiasis cases per 100 000 travellers and compared the incidence in 2014-16 and 2017-19 to identify potential trends. RESULTS: In 2014-19, 21 172 giardiasis cases were reported in Germany, corresponding to an overall incidence of 4.3 per 100 000 population. Of all cases, 6879 (32%) were travel-related with a median age of 34 [interquartile range (IQR): 25-50], 51% were male. Southern Asia was the most frequently reported exposure region and had the highest incidence in travellers (64.1 per 100 000 returning travellers) in 2017-19, followed by Latin America (19.2) and Sub-Saharan Africa (12.9). We observed statistically significant decreasing trends for Southern Asia and Sub-Saharan Africa. Latin America was the only region with a statistically significant increasing trend. CONCLUSIONS: Almost one-third of recent giardiasis cases in Germany were travel-related. Giardiasis incidence in travellers differs greatly depending on the destination region. Decreasing trends in many regions might be due to improvements in food hygiene or travel conditions. Our results may inform medical consultation pre and post patient's travel.

Bayesian reconstruction of SARS-CoV-2 transmissions highlights substantial proportion of negative serial intervals.

BACKGROUND: The serial interval is a key epidemiological measure that quantifies the time between the onset of symptoms in an infector-infectee pair. It indicates how quickly new generations of cases appear, thus informing on the speed of an epidemic. Estimating the serial interval requires to identify pairs of infectors and infectees. Yet, most studies fail to assess the direction of transmission between cases and assume that the order of infections - and thus transmissions - strictly follows the order of symptom onsets, thereby imposing serial intervals to be positive. Because of the long and highly variable incubation period of SARS-CoV-2, this may not always be true (i.e an infectee may show symptoms before their infector) and negative serial intervals may occur. This study aims to estimate the serial interval of different SARS-CoV-2 variants whilst accounting for negative serial intervals. METHODS: This analysis included 5 842 symptomatic individuals with confirmed SARS-CoV-2 infection amongst 2 579 households from September 2020 to August 2022 across England & Wales. We used a Bayesian framework to infer who infected whom by exploring all transmission trees compatible with the observed dates of symptoms, based on a wide range of incubation period and generation time distributions compatible with estimates reported in the literature. Serial intervals were derived from the reconstructed transmission pairs, stratified by variants. RESULTS: We estimated that 22% (95% credible interval (CrI) 8-32%) of serial interval values are negative across all VOC. The mean serial interval was shortest for Omicron BA5 (2.02 days, 1.26-2.84) and longest for Alpha (3.37 days, 2.52-4.04). CONCLUSIONS: This study highlights the large proportion of negative serial intervals across SARS-CoV-2 variants. Because the serial interval is widely used to estimate transmissibility and forecast cases, these results may have critical implications for epidemic control.

Extending EpiEstim to estimate the transmission advantage of pathogen variants in real-time: SARS-CoV-2 as a case-study.

The evolution of SARS-CoV-2 has demonstrated that emerging variants can set back the global COVID-19 response. The ability to rapidly assess the threat of new variants is critical for timely optimisation of control strategies. We present a novel method to estimate the effective transmission advantage of a new variant compared to a reference variant combining information across multiple locations and over time. Through an extensive simulation study designed to mimic real-time epidemic contexts, we show that our method performs well across a range of scenarios and provide guidance on its optimal use and interpretation of results. We also provide an open-source software implementation of our method. The computational speed of our tool enables users to rapidly explore spatial and temporal variations in the estimated transmission advantage. We estimate that the SARS-CoV-2 Alpha variant is 1.46 (95% Credible Interval 1.44-1.47) and 1.29 (95% CrI 1.29-1.30) times more transmissible than the wild type, using data from England and France respectively. We further estimate that Delta is 1.77 (95% CrI 1.69-1.85) times more transmissible than Alpha (England data). Our approach can be used as an important first step towards quantifying the threat of emerging or co-circulating variants of infectious pathogens in real-time.

Comparing Mycobacterium tuberculosis transmission reconstruction models from whole genome sequence data.

Genomic epidemiology is routinely used worldwide to interrogate infectious disease dynamics. Multiple computational tools exist that reconstruct transmission networks by coupling genomic data with epidemiological models. Resulting inferences can improve our understanding of pathogen transmission dynamics, and yet the performance of these tools has not been evaluated for tuberculosis (TB), a disease process with complex epidemiology including variable latency and within-host heterogeneity. Here, we performed a systematic comparison of six publicly available transmission reconstruction models, evaluating their accuracy when predicting transmission events in simulated and real-world Mycobacterium tuberculosis outbreaks. We observed variability in the number of transmission links that were predicted with high probability (P ≥ 0.5) and low accuracy of these predictions against known transmission in simulated outbreaks. We also found a low proportion of epidemiologically supported case-contact pairs were identified in our real-world TB clusters. The specificity of all models was high, and a relatively high proportion of the total transmission events predicted by some models were true links, notably with TransPhylo, Outbreaker2, and Phybreak. Our findings may inform the choice of tools in TB transmission analyses and underscore the need for caution when interpreting transmission networks produced using probabilistic approaches.

Icteric Leptospirosis Leading to Multiorgan Failure and Concomitant Pancreatitis.

Leptospirosis is a zoonotic disease caused by the spirochete Leptospira interrogans with a majority of cases occurring in the tropics. Diagnosing leptospirosis is challenging due to the variable and non-specific clinical presentation. While severe leptospirosis may present with renal failure, liver failure, and pulmonary hemorrhage, there are few described cases of renal failure and liver failure accompanied by pancreatitis and dysrhythmias, particularly in temperate climates. We present a case of severe leptospirosis presenting with bilateral calf pain, acute oliguric renal failure, acute liver failure, dysrhythmias, and pancreatitis. Clinicians must consider this diagnosis in temperate climates and consider testing and empirically treating for leptospirosis in patients with similar symptom constellations, vague symptoms, and lab abnormalities of unknown etiology.

Genetic and epidemiological analyses of infection load and its relationship with psychiatric disorders.

Severe infections and psychiatric disorders have a large impact on both society and the individual. Studies investigating these conditions and the links between them are therefore important. Most past studies have focused on binary phenotypes of particular infections or overall infection, thereby losing some information regarding susceptibility to infection as reflected in the number of specific infection types, or sites, which we term infection load. In this study we found that infection load was associated with increased risk for attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, depression, schizophrenia and overall psychiatric diagnosis. We obtained a modest but significant heritability for infection load (h2 = 0.0221), and a high degree of genetic correlation between it and overall psychiatric diagnosis (rg = 0.4298). We also found evidence supporting a genetic causality for overall infection on overall psychiatric diagnosis. Our genome-wide association study for infection load identified 138 suggestive associations. Our study provides further evidence for genetic links between susceptibility to infection and psychiatric disorders, and suggests that a higher infection load may have a cumulative association with psychiatric disorders, beyond what has been described for individual infections.

Demographic and clinical characteristics of children and adolescents hospitalised with laboratory-confirmed COVID-19 in the Tel-Aviv District, Israel, 2020-2022.

Our study population consisted of all children and adolescents, with laboratory-confirmed SARS-Co-V-2 infection, hospitalised from February 2020 through February 2022, among residents of the Tel Aviv (TA) District, Israel. There were 491 children and adolescents hospitalised with Sars-CoV-2 infection. Among them, 281 (57%) admitted with coronavirus disease 2019 (COVID-19) as the primary cause of admission (rate of 39 per 100 000). Among all children and adolescents in the TA District, the highest hospitalisation rates were observed among infants and children below the age of 4 years (rate of 311 per 100 000 population). Severe disease was observed mostly among children with multiple underlying medical conditions. Admission rates were also elevated among residents of the ultra-orthodox community (rate ratio (RR) compared to the rest of the district; 95% confidence interval (CI) 2.38-3.82). Admission rates with COVID-19 as primary cause of admission were higher during Omicron compared to Delta predominance period (RR 1.7; 95% CI 1.22-2.32). Targeted social and public health policies should be put in place when rates of disease start to increase, such as encouraging vaccine uptake for eligible children and social distancing when necessary, taking into account already existing social and learning gaps, in order to reduce the burden of disease.

Usefulness of linked data for infectious disease events: a systematic review.

Surveillance is a key public health function to enable early detection of infectious disease events and inform public health action. Data linkage may improve the depth of data for response to infectious disease events. This study aimed to describe the uses of linked data for infectious disease events. A systematic review was conducted using Pubmed, CINAHL and Web of Science. Studies were included if they used data linkage for an acute infectious disease event (e.g. outbreak of disease). We summarised the event, study aims and designs; data sets; linkage methods; outcomes reported; and benefits and limitations. Fifty-four studies were included. Uses of linkage for infectious disease events included assessment of severity of disease and risk factors; improved case finding and contact tracing; and vaccine uptake, safety and effectiveness. The ability to conduct larger scale population level studies was identified as a benefit, in particular for rarer exposures, risk factors or outcomes. Limitations included timeliness, data quality and inability to collect additional variables. This review demonstrated multiple uses of data linkage for infectious disease events. As infectious disease events occur without warning, there is a need to establish pre-approved protocols and the infrastructure for data-linkage to enhance information available during an event.

A practical guide to mathematical methods for estimating infectious disease outbreak risks.

Mathematical models are increasingly used throughout infectious disease outbreaks to guide control measures. In this review article, we focus on the initial stages of an outbreak, when a pathogen has just been observed in a new location (e.g., a town, region or country). We provide a beginner's guide to two methods for estimating the risk that introduced cases lead to sustained local transmission (i.e., the probability of a major outbreak), as opposed to the outbreak fading out with only a small number of cases. We discuss how these simple methods can be extended for epidemiological models with any level of complexity, facilitating their wider use, and describe how estimates of the probability of a major outbreak can be used to guide pathogen surveillance and control strategies. We also give an overview of previous applications of these approaches. This guide is intended to help quantitative researchers develop their own epidemiological models and use them to estimate the risks associated with pathogens arriving in new host populations. The development of these models is crucial for future outbreak preparedness. This manuscript was submitted as part of a theme issue on "Modelling COVID-19 and Preparedness for Future Pandemics".

Effect of the incremental protection of previous infection against Omicron infection among individuals with a hybrid of infection- and vaccine-induced immunity: a population-based cohort study in Canada.

OBJECTIVES: We examined the incremental protection and durability of infection-acquired immunity against Omicron infection in individuals with hybrid immunity in Ontario, Canada. METHODS: We followed up 6 million individuals with at least one multiplex reverse transcriptase-polymerase chain reaction test before November 21, 2021, until an Omicron infection. Protection via infection-acquired immunity was assessed by comparing Omicron infection risk between previously infected individuals and those without documented infection under different vaccination scenarios and stratified by time since the last infection or vaccination. RESULTS: A previous infection was associated with 68% (95% CI 61-73) and 43% (95% CI 27-56) increased protection against Omicron infection in individuals with two and three doses, respectively. Among individuals with two-dose vaccination, the incremental protection of infection-induced immunity decreased from 79% (95% CI 75-81) within 3 months after vaccination or infection to 27% (95% CI 14-37) at 9-11 months. In individuals with three-dose vaccination, it decreased from 57% (95% CI 50-63) within 3 months to 37% (95% CI 19-51) at 3-5 months after vaccination or infection. CONCLUSION: Previous SARS-CovV-2 infections provide added cross-variant immunity to vaccination. Given the limited durability of infection-acquired protection in individuals with hybrid immunity, its influence on shield-effects at the population level and reinfection risks at the individual level may be limited.

Evidence of within-facility patient-patient Clostridiodes difficile infection spread across diverse settings.

Previous studies have suggested that a hospital patient's risk of developing healthcare facility-onset (HCFO) Clostridioides difficile infections (CDIs) increases with the number of concurrent spatially proximate patients with CDI, termed CDI pressure. However, these studies were performed either in a single institution or in a single state with a very coarse measure of concurrence. We conducted a retrospective case-control study involving over 17.5 million inpatient visits across 700 hospitals in eight US states. We built a weighted, directed network connecting overlapping inpatient visits to measure facility-level CDI pressure. We then matched HCFO-CDIs with non-CDI controls on facility, comorbidities and demographics and performed a conditional logistic regression to determine the odds of developing HCFO-CDI given the number of coincident patient visits with CDI. On average, cases' visits coincided with 9.2 CDI cases, which for an individual with an average length of stay corresponded to an estimated 17.7% (95% CI 12.9-22.7%) increase in the odds of acquiring HCFO-CDI compared to an inpatient visit without concurrent CDI cases or fully isolated from both direct and indirect risks from concurrent CDI cases. These results suggest that, either directly or indirectly, hospital patients with CDI lead to CDIs in non-infected patients with temporally overlapping visits.