The interactions of SARS-CoV-2 with cocirculating pathogens: Epidemiological implications and current knowledge gaps.

Despite the availability of effective vaccines, the persistence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) suggests that cocirculation with other pathogens and resulting multiepidemics (of, for example, COVID-19 and influenza) may become increasingly frequent. To better forecast and control the risk of such multiepidemics, it is essential to elucidate the potential interactions of SARS-CoV-2 with other pathogens; these interactions, however, remain poorly defined. Here, we aimed to review the current body of evidence about SARS-CoV-2 interactions. Our review is structured in four parts. To study pathogen interactions in a systematic and comprehensive way, we first developed a general framework to capture their major components: sign (either negative for antagonistic interactions or positive for synergistic interactions), strength (i.e., magnitude of the interaction), symmetry (describing whether the interaction depends on the order of infection of interacting pathogens), duration (describing whether the interaction is short-lived or long-lived), and mechanism (e.g., whether interaction modifies susceptibility to infection, transmissibility of infection, or severity of disease). Second, we reviewed the experimental evidence from animal models about SARS-CoV-2 interactions. Of the 14 studies identified, 11 focused on the outcomes of coinfection with nonattenuated influenza A viruses (IAVs), and 3 with other pathogens. The 11 studies on IAV used different designs and animal models (ferrets, hamsters, and mice) but generally demonstrated that coinfection increased disease severity compared with either monoinfection. By contrast, the effect of coinfection on the viral load of either virus was variable and inconsistent across studies. Third, we reviewed the epidemiological evidence about SARS-CoV-2 interactions in human populations. Although numerous studies were identified, only a few were specifically designed to infer interaction, and many were prone to multiple biases, including confounding. Nevertheless, their results suggested that influenza and pneumococcal conjugate vaccinations were associated with a reduced risk of SARS-CoV-2 infection. Finally, fourth, we formulated simple transmission models of SARS-CoV-2 cocirculation with an epidemic viral pathogen or an endemic bacterial pathogen, showing how they can naturally incorporate the proposed framework. More generally, we argue that such models, when designed with an integrative and multidisciplinary perspective, will be invaluable tools to resolve the substantial uncertainties that remain about SARS-CoV-2 interactions.

An algorithm to build synthetic temporal contact networks based on close-proximity interactions data.

Small populations (e.g., hospitals, schools or workplaces) are characterised by high contact heterogeneity and stochasticity affecting pathogen transmission dynamics. Empirical individual contact data provide unprecedented information to characterize such heterogeneity and are increasingly available, but are usually collected over a limited period, and can suffer from observation bias. We propose an algorithm to stochastically reconstruct realistic temporal networks from individual contact data in healthcare settings (HCS) and test this approach using real data previously collected in a long-term care facility (LTCF). Our algorithm generates full networks from recorded close-proximity interactions, using hourly inter-individual contact rates and information on individuals' wards, the categories of staff involved in contacts, and the frequency of recurring contacts. It also provides data augmentation by reconstructing contacts for days when some individuals are present in the HCS without having contacts recorded in the empirical data. Recording bias is formalized through an observation model, to allow direct comparison between the augmented and observed networks. We validate our algorithm using data collected during the i-Bird study, and compare the empirical and reconstructed networks. The algorithm was substantially more accurate to reproduce network characteristics than random graphs. The reconstructed networks reproduced well the assortativity by ward (first-third quartiles observed: 0.54-0.64; synthetic: 0.52-0.64) and the hourly staff and patient contact patterns. Importantly, the observed temporal correlation was also well reproduced (0.39-0.50 vs 0.37-0.44), indicating that our algorithm could recreate a realistic temporal structure. The algorithm consistently recreated unobserved contacts to generate full reconstructed networks for the LTCF. To conclude, we propose an approach to generate realistic temporal contact networks and reconstruct unobserved contacts from summary statistics computed using individual-level interaction networks. This could be applied and extended to generate contact networks to other HCS using limited empirical data, to subsequently inform individual-based epidemic models.

Using contact network dynamics to implement efficient interventions against pathogen spread in hospital settings: A modelling study.

BACKGROUND: Long-term care facilities (LTCFs) are hotspots for pathogen transmission. Infection control interventions are essential, but the high density and heterogeneity of interindividual contacts within LTCF may hinder their efficacy. Here, we explore how the patient-staff contact structure may inform effective intervention implementation. METHODS AND FINDINGS: Using an individual-based model (IBM), we reproduced methicillin-resistant Staphylococcus aureus colonisation transmission dynamics over a detailed contact network recorded within a French LTCF of 327 patients and 263 staff over 3 months. Simulated baseline cumulative colonisation incidence was 21 patients (prediction interval: 11, 31) and 35 staff (prediction interval: 19, 54). We examined the potential impact of 3 types of interventions against transmission (reallocation reducing the number of unique contacts per staff, reinforced contact precautions, and hypothetical vaccination protecting against acquisition), targeted towards specific populations. All 3 interventions were effective when applied to all nurses or healthcare assistants (median reduction in MRSA colonisation incidence up to 35%), but the benefit did not exceed 8% when targeting any other single staff category. We identified "supercontactor" individuals with most contacts ("frequency-based," overrepresented among nurses, porters, and rehabilitation staff) or with the longest cumulative time spent in contact ("duration-based," overrepresented among healthcare assistants and patients in elderly care or persistent vegetative state (PVS)). Targeting supercontactors enhanced interventions against pathogen spread in the LTCF. With contact precautions, targeting frequency-based staff supercontactors led to the highest incidence reduction (20%, 95% CI: 19, 21). Vaccinating a mix of frequency- and duration-based staff supercontactors led to a higher reduction (23%, 95% CI: 22, 24) than all other approaches. Although based on data from a single LTCF, when varying epidemiological parameters to extend to other pathogens, our results suggest that targeting supercontactors is always the most effective strategy, indicating this approach could be applied to prevent transmission of other nosocomial pathogens. CONCLUSIONS: By characterising the contact structure in hospital settings and identifying the categories of staff and patients more likely to be supercontactors, with either more or longer contacts than others, interventions against nosocomial spread could be more effective. We find that the most efficient implementation strategy depends on the intervention (reallocation, contact precautions, vaccination) and target population (staff, patients, supercontactors). Importantly, both staff and patients may be supercontactors, highlighting the importance of including patients in measures to prevent pathogen transmission in LTCF.

Risk Factors for Community and Intrahousehold Transmission of SARS-CoV-2: Modeling in a Nationwide French Population-Based Cohort Study, the EpiCoV Study.

We assessed the risk of acquiring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from household and community exposure according to age, family ties, and socioeconomic and living conditions using serological data from a nationwide French population-based cohort study, the Epidémiologie et Conditions de Vie (EpiCoV) Study. A history of SARS-CoV-2 infection was defined by a positive anti-SARS-CoV-2 enzyme-linked immunosorbent assay immunoglobulin G result in November-December 2020. We applied stochastic chain binomial models fitted to the final distribution of household infections to data from 17,983 individuals aged ≥6 years from 8,165 households. Models estimated the competing risks of being infected from community and household exposure. The age group 18-24 years had the highest risk of extrahousehold infection (8.9%, 95% credible interval (CrI): 7.5, 10.4), whereas the oldest (≥75 years) and youngest (6-10 years) age groups had the lowest risk, at 2.6% (95% CrI: 1.8, 3.5) and 3.4% (95% CrI: 1.9, 5.2), respectively. Extrahousehold infection was also associated with socioeconomic conditions. Within households, the probability of person-to-person transmission increased with age, from 10.6% (95% CrI: 5.0, 17.9) among children aged 6-10 years to 43.1% (95% CrI: 32.6, 53.2) among adults aged 65-74 years. Transmission was higher between partners (29.9%, 95% CrI: 25.6, 34.3) and from mother to child (29.1%, 95% CrI: 21.4, 37.3) than between individuals related by other family ties. In 2020 in France, the main factors identified for extrahousehold SARS-CoV-2 infection were age and socioeconomic conditions. Intrahousehold infection mainly depended on age and family ties.

Collateral impacts of pandemic COVID-19 drive the nosocomial spread of antibiotic resistance: A modelling study.

BACKGROUND: Circulation of multidrug-resistant bacteria (MRB) in healthcare facilities is a major public health problem. These settings have been greatly impacted by the Coronavirus Disease 2019 (COVID-19) pandemic, notably due to surges in COVID-19 caseloads and the implementation of infection control measures. We sought to evaluate how such collateral impacts of COVID-19 impacted the nosocomial spread of MRB in an early pandemic context. METHODS AND FINDINGS: We developed a mathematical model in which Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and MRB cocirculate among patients and staff in a theoretical hospital population. Responses to COVID-19 were captured mechanistically via a range of parameters that reflect impacts of SARS-CoV-2 outbreaks on factors relevant for pathogen transmission. COVID-19 responses include both "policy responses" willingly enacted to limit SARS-CoV-2 transmission (e.g., universal masking, patient lockdown, and reinforced hand hygiene) and "caseload responses" unwillingly resulting from surges in COVID-19 caseloads (e.g., abandonment of antibiotic stewardship, disorganization of infection control programmes, and extended length of stay for COVID-19 patients). We conducted 2 main sets of model simulations, in which we quantified impacts of SARS-CoV-2 outbreaks on MRB colonization incidence and antibiotic resistance rates (the share of colonization due to antibiotic-resistant versus antibiotic-sensitive strains). The first set of simulations represents diverse MRB and nosocomial environments, accounting for high levels of heterogeneity across bacterial parameters (e.g., rates of transmission, antibiotic sensitivity, and colonization prevalence among newly admitted patients) and hospital parameters (e.g., rates of interindividual contact, antibiotic exposure, and patient admission/discharge). On average, COVID-19 control policies coincided with MRB prevention, including 28.2% [95% uncertainty interval: 2.5%, 60.2%] fewer incident cases of patient MRB colonization. Conversely, surges in COVID-19 caseloads favoured MRB transmission, resulting in a 13.8% [-3.5%, 77.0%] increase in colonization incidence and a 10.4% [0.2%, 46.9%] increase in antibiotic resistance rates in the absence of concomitant COVID-19 control policies. When COVID-19 policy responses and caseload responses were combined, MRB colonization incidence decreased by 24.2% [-7.8%, 59.3%], while resistance rates increased by 2.9% [-5.4%, 23.2%]. Impacts of COVID-19 responses varied across patients and staff and their respective routes of pathogen acquisition. The second set of simulations was tailored to specific hospital wards and nosocomial bacteria (methicillin-resistant Staphylococcus aureus, extended-spectrum beta-lactamase producing Escherichia coli). Consequences of nosocomial SARS-CoV-2 outbreaks were found to be highly context specific, with impacts depending on the specific ward and bacteria evaluated. In particular, SARS-CoV-2 outbreaks significantly impacted patient MRB colonization only in settings with high underlying risk of bacterial transmission. Yet across settings and species, antibiotic resistance burden was reduced in facilities with timelier implementation of effective COVID-19 control policies. CONCLUSIONS: Our model suggests that surges in nosocomial SARS-CoV-2 transmission generate selection for the spread of antibiotic-resistant bacteria. Timely implementation of efficient COVID-19 control measures thus has 2-fold benefits, preventing the transmission of both SARS-CoV-2 and MRB, and highlighting antibiotic resistance control as a collateral benefit of pandemic preparedness.

Ability of epidemiological studies to monitor HPV post-vaccination dynamics: a simulation study.

Genital human papillomavirus (HPV) infections are caused by a broad diversity of genotypes. As available vaccines target a subgroup of these genotypes, monitoring transmission dynamics of nonvaccine genotypes is essential. After reviewing the epidemiological literature on study designs aiming to monitor those dynamics, we evaluated their abilities to detect HPV-prevalence changes following vaccine introduction. We developed an agent-based model to simulate HPV transmission in a heterosexual population under various scenarios of vaccine coverage and genotypic interaction, and reproduced two study designs: post-vs.-prevaccine and vaccinated-vs.-unvaccinated comparisons. We calculated the total sample size required to detect statistically significant prevalence differences at the 5% significance level and 80% power. Although a decrease in vaccine-genotype prevalence was detectable as early as 1 year after vaccine introduction, simulations indicated that the indirect impact on nonvaccine-genotype prevalence (a decrease under synergistic interaction or an increase under competitive interaction) would only be measurable after >10 years whatever the vaccine coverage. Sample sizes required for nonvaccine genotypes were >5 times greater than for vaccine genotypes and tended to be smaller in the post-vs.-prevaccine than in the vaccinated-vs.-unvaccinated design. These results highlight that previously published epidemiological studies were not powerful enough to efficiently detect changes in nonvaccine-genotype prevalence.

The Impact of Cocirculating Pathogens on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)/Coronavirus Disease 2019 Surveillance: How Concurrent Epidemics May Introduce Bias and Decrease the Observed SARS-CoV-2 Percentage Positivity.

BACKGROUND: Circulation of seasonal non-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) respiratory viruses with syndromic overlap during the coronavirus disease 2019 (COVID-19) pandemic may alter the quality of COVID-19 surveillance, with possible consequences for real-time analysis and delay in implementation of control measures. METHODS: Using a multipathogen susceptible-exposed-infectious-recovered (SEIR) transmission model formalizing cocirculation of SARS-CoV-2 and another respiratory virus, we assessed how an outbreak of secondary virus may affect 2 COVID-19 surveillance indicators: testing demand and positivity. Using simulation, we assessed to what extent the use of multiplex polymerase chain reaction tests on a subsample of symptomatic individuals can help correct the observed SARS-CoV-2 percentage positivity and improve surveillance quality. RESULTS: We find that a non-SARS-CoV-2 epidemic strongly increases SARS-CoV-2 daily testing demand and artificially reduces the observed SARS-CoV-2 percentage positivity for the duration of the outbreak. We estimate that performing 1 multiplex test for every 1000 COVID-19 tests on symptomatic individuals could be sufficient to maintain surveillance of other respiratory viruses in the population and correct the observed SARS-CoV-2 percentage positivity. CONCLUSIONS: This study showed that cocirculating respiratory viruses can distort SARS-CoV-2 surveillance. Correction of the positivity rate can be achieved by using multiplex polymerase chain reaction tests, and a low number of samples is sufficient to avoid bias in SARS-CoV-2 surveillance.

Measuring Basic Reproduction Number to Assess Effects of Nonpharmaceutical Interventions on Nosocomial SARS-CoV-2 Transmission.

Outbreaks of SARS-CoV-2 infection frequently occur in hospitals. Preventing nosocomial infection requires insight into hospital transmission. However, estimates of the basic reproduction number (R0) in care facilities are lacking. Analyzing a closely monitored SARS-CoV-2 outbreak in a hospital in early 2020, we estimated the patient-to-patient transmission rate and R0. We developed a model for SARS-CoV-2 nosocomial transmission that accounts for stochastic effects and undetected infections and fit it to patient test results. The model formalizes changes in testing capacity over time, and accounts for evolving PCR sensitivity at different stages of infection. R0 estimates varied considerably across wards, ranging from 3 to 15 in different wards. During the outbreak, the hospital introduced a contact precautions policy. Our results strongly support a reduction in the hospital-level R0 after this policy was implemented, from 8.7 to 1.3, corresponding to a policy efficacy of 85% and demonstrating the effectiveness of nonpharmaceutical interventions.

Mitigating COVID-19 outbreaks in workplaces and schools by hybrid telecommuting.

The COVID-19 epidemic has forced most countries to impose contact-limiting restrictions at workplaces, universities, schools, and more broadly in our societies. Yet, the effectiveness of these unprecedented interventions in containing the virus spread remain largely unquantified. Here, we develop a simulation study to analyze COVID-19 outbreaks on three real-life contact networks stemming from a workplace, a primary school and a high school in France. Our study provides a fine-grained analysis of the impact of contact-limiting strategies at workplaces, schools and high schools, including: (1) Rotating strategies, in which workers are evenly split into two shifts that alternate on a daily or weekly basis; and (2) On-Off strategies, where the whole group alternates periods of normal work interactions with complete telecommuting. We model epidemics spread in these different setups using a stochastic discrete-time agent-based transmission model that includes the coronavirus most salient features: super-spreaders, infectious asymptomatic individuals, and pre-symptomatic infectious periods. Our study yields clear results: the ranking of the strategies, based on their ability to mitigate epidemic propagation in the network from a first index case, is the same for all network topologies (workplace, primary school and high school). Namely, from best to worst: Rotating week-by-week, Rotating day-by-day, On-Off week-by-week, and On-Off day-by-day. Moreover, our results show that below a certain threshold for the original local reproduction number [Formula: see text] within the network (< 1.52 for primary schools, < 1.30 for the workplace, < 1.38 for the high school, and < 1.55 for the random graph), all four strategies efficiently control outbreak by decreasing effective local reproduction number to [Formula: see text] < 1. These results can provide guidance for public health decisions related to telecommuting.

Retrospective analysis of SARS-CoV-2 omicron invasion over delta in French regions in 2021-22: a status-based multi-variant model.

BACKGROUND: SARS-CoV-2 is a rapidly spreading disease affecting human life and the economy on a global scale. The disease has caused so far more then 5.5 million deaths. The omicron outbreak that emerged in Botswana in the south of Africa spread around the globe at further increased rates, and caused unprecedented SARS-CoV-2 infection incidences in several countries. At the start of December 2021 the first omicron cases were reported in France. METHODS: In this paper we investigate the spreading potential of this novel variant relatively to the delta variant that was also in circulation in France at that time. Using a dynamic multi-variant model accounting for cross-immunity through a status-based approach, we analyze screening data reported by Santé Publique France over 13 metropolitan French regions between 1st of December 2021 and the 30th of January 2022. During the investigated period, the delta variant was replaced by omicron in all metropolitan regions in approximately three weeks. The analysis conducted retrospectively allows us to consider the whole replacement time window and compare regions with different times of omicron introduction and baseline levels of variants' transmission potential. As large uncertainties regarding cross-immunity among variants persist, uncertainty analyses were carried out to assess its impact on our estimations. RESULTS: Assuming that 80% of the population was immunized against delta, a cross delta/omicron cross-immunity of 25% and an omicron generation time of 3.5 days, the relative strength of omicron to delta, expressed as the ratio of their respective reproduction rates, [Formula: see text], was found to range between 1.51 and 1.86 across regions. Uncertainty analysis on epidemiological parameters led to [Formula: see text] ranging from 1.57 to 2.34 on average over the metropolitan French regions, weighted by population size. CONCLUSIONS: Upon introduction, omicron spread rapidly through the French territory and showed a high fitness relative to delta. We documented considerable geographical heterogeneities on the spreading dynamics. The historical reconstruction of variant emergence dynamics provide valuable ground knowledge to face future variant emergence events.

Unraveling the seasonal epidemiology of pneumococcus.

Infections caused by Streptococcus pneumoniae-including invasive pneumococcal diseases (IPDs)-remain a significant public health concern worldwide. The marked winter seasonality of IPDs is a striking, but still enigmatic aspect of pneumococcal epidemiology in nontropical climates. Here we confronted age-structured dynamic models of carriage transmission and disease with detailed IPD incidence data to test a range of hypotheses about the components and the mechanisms of pneumococcal seasonality. We find that seasonal variations in climate, influenza-like illnesses, and interindividual contacts jointly explain IPD seasonality. We show that both the carriage acquisition rate and the invasion rate vary seasonally, acting in concert to generate the marked seasonality typical of IPDs. We also find evidence that influenza-like illnesses increase the invasion rate in an age-specific manner, with a more pronounced effect in the elderly than in other demographics. Finally, we quantify the potential impact of seasonally timed interventions, a type of control measures that exploit pneumococcal seasonality to help reduce IPDs. Our findings shed light on the epidemiology of pneumococcus and may have notable implications for the control of pneumococcal infections.

A Conceptual Discussion About the Basic Reproduction Number of Severe Acute Respiratory Syndrome Coronavirus 2 in Healthcare Settings.

To date, no specific estimate of R0 for SARS-CoV-2 is available for healthcare settings. Using interindividual contact data, we highlight that R0 estimates from the community cannot translate directly to healthcare settings, with pre-pandemic R0 values ranging 1.3-7.7 in 3 illustrative healthcare institutions. This has implications for nosocomial COVID-19 control.

A One-Health Quantitative Model to Assess the Risk of Antibiotic Resistance Acquisition in Asian Populations: Impact of Exposure Through Food, Water, Livestock and Humans.

Antimicrobial resistance (AMR) has become a major threat worldwide, especially in countries with inadequate sanitation and low antibiotic regulation. However, adequately prioritizing AMR interventions in such settings requires a quantification of the relative impacts of environmental, animal, and human sources in a One-Health perspective. Here, we propose a stochastic quantitative risk assessment model for the different components at interplay in AMR selection and spread. The model computes the incidence of AMR colonization in humans from five different sources: water or food consumption, contacts with livestock, and interhuman contacts in hospitals or the community, and combines these incidences into a per-year acquisition risk. Using data from the literature and Monte-Carlo simulations, we apply the model to hypothetical Asian-like settings, focusing on resistant bacteria that may cause infections in humans. In both scenarios A, illustrative of low-income countries, and B, illustrative of high-income countries, the overall individual risk of becoming colonized with resistant bacteria at least once per year is high. However, the average predicted incidence of colonization was lower in scenario B at 0.82 (CrI [0.13, 5.1]) acquisitions/person/year, versus 1.69 (CrI [0.66, 11.13]) acquisitions/person/year for scenario A. A high percentage of population with no access to improved water on premises and a high percentage of population involved in husbandry are shown to strongly increase the AMR acquisition risk. The One-Health AMR risk assessment framework we developed may prove useful to policymakers throughout Asia, as it can easily be parameterized to realistically reproduce conditions in a given country, provided data are available.

Lockdown impact on age-specific contact patterns and behaviours, France, April 2020.

BackgroundMany countries implemented national lockdowns to contain the rapid spread of SARS-CoV-2 and avoid overburdening healthcare capacity.AimWe aimed to quantify how the French lockdown impacted population mixing, contact patterns and behaviours.MethodsWe conducted an online survey using convenience sampling and collected information from participants aged 18 years and older between 10 April and 28 April 2020.ResultAmong the 42,036 survey participants, 72% normally worked outside their home, and of these, 68% changed to telework during lockdown and 17% reported being unemployed during lockdown. A decrease in public transport use was reported from 37% to 2%. Participants reported increased frequency of hand washing and changes in greeting behaviour. Wearing masks in public was generally limited. A total of 138,934 contacts were reported, with an average of 3.3 contacts per individual per day; 1.7 in the participants aged 65 years and older compared with 3.6 for younger age groups. This represented a 70% reduction compared with previous surveys, consistent with SARS-CoV2 transmission reduction measured during the lockdown. For those who maintained a professional activity outside home, the frequency of contacts at work dropped by 79%.ConclusionThe lockdown affected the population's behaviour, work, risk perception and contact patterns. The frequency and heterogeneity of contacts, both of which are critical factors in determining how viruses spread, were affected. Such surveys are essential to evaluate the impact of lockdowns more accurately and anticipate epidemic dynamics in these conditions.

Transmissibility and pathogenicity of the emerging meningococcal serogroup W sequence type-11 complex South American strain: a mathematical modeling study.

BACKGROUND: The recent emergence of strains belonging to the meningococcal serogroup W (MenW) sequence type-11 clonal complex and descending from the South American sub-lineage (MenW:cc11/SA) has caused significant shifts in the epidemiology of meningococcal disease worldwide. Although MenW:cc11/SA is deemed highly transmissible and invasive, its epidemiological characteristics have not yet been quantified. METHODS: We designed a mathematical model of MenW transmission, carriage, and infection to analyze the recent epidemiology of invasive disease caused by MenW:cc11/SA strains and by other MenW strains in England and in France. We confronted that model with age-stratified incidence data to estimate the transmissibility and the invasiveness of MenW:cc11/SA in England, using the data in France as a validation cohort. RESULTS: During the epidemiological years 2010/2011-2014/2015 in England, the transmissibility of MenW:cc11/SA relative to that of other MenW strains was estimated at 1.20 (95% confidence interval, 1.15 to 1.26). The relative invasiveness of MenW:cc11/SA was also found to exceed unity and to increase with age, with estimates ranging from 4.0 (1.6 to 9.7) in children aged 0-4 years to 20 (6 to 34) in adults aged ≥ 25 years. In France, the model calibrated in England correctly reproduced the early increase of MenW:cc11/SA disease during 2012/2013-2016/2017. Most recent surveillance data, however, indicated a decline in MenW:cc11/SA disease. In both countries, our results suggested that the transmission of MenW:cc11/SA carriage possibly started several months before the first reported case of MenW:cc11/SA disease. DISCUSSION: Our results confirm earlier suggestions about the transmission and the pathogenic potential of MenW:cc11/SA. The main limitation of our study was the lack of age-specific MenW carriage data to confront our model predictions with. Furthermore, the lesser model fit to the most recent data in France suggests that the predictive accuracy of our model might be limited to 5-6 years. CONCLUSIONS: Our study provides the first estimates of the transmissibility and of the invasiveness of MenW:cc11/SA. Such estimates may be useful to anticipate changes in the epidemiology of MenW and to adapt vaccination strategies. Our results also point to silent, prolonged transmission of MenW:cc11/SA carriage, with potentially important implications for epidemic preparedness.

Optimizing COVID-19 surveillance in long-term care facilities: a modelling study.

BACKGROUND: Long-term care facilities (LTCFs) are vulnerable to outbreaks of coronavirus disease 2019 (COVID-19). Timely epidemiological surveillance is essential for outbreak response, but is complicated by a high proportion of silent (non-symptomatic) infections and limited testing resources. METHODS: We used a stochastic, individual-based model to simulate transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) along detailed inter-individual contact networks describing patient-staff interactions in a real LTCF setting. We simulated distribution of nasopharyngeal swabs and reverse transcriptase polymerase chain reaction (RT-PCR) tests using clinical and demographic indications and evaluated the efficacy and resource-efficiency of a range of surveillance strategies, including group testing (sample pooling) and testing cascades, which couple (i) testing for multiple indications (symptoms, admission) with (ii) random daily testing. RESULTS: In the baseline scenario, randomly introducing a silent SARS-CoV-2 infection into a 170-bed LTCF led to large outbreaks, with a cumulative 86 (95% uncertainty interval 6-224) infections after 3 weeks of unmitigated transmission. Efficacy of symptom-based screening was limited by lags to symptom onset and silent asymptomatic and pre-symptomatic transmission. Across scenarios, testing upon admission detected just 34-66% of patients infected upon LTCF entry, and also missed potential introductions from staff. Random daily testing was more effective when targeting patients than staff, but was overall an inefficient use of limited resources. At high testing capacity (> 10 tests/100 beds/day), cascades were most effective, with a 19-36% probability of detecting outbreaks prior to any nosocomial transmission, and 26-46% prior to first onset of COVID-19 symptoms. Conversely, at low capacity (< 2 tests/100 beds/day), group testing strategies detected outbreaks earliest. Pooling randomly selected patients in a daily group test was most likely to detect outbreaks prior to first symptom onset (16-27%), while pooling patients and staff expressing any COVID-like symptoms was the most efficient means to improve surveillance given resource limitations, compared to the reference requiring only 6-9 additional tests and 11-28 additional swabs to detect outbreaks 1-6 days earlier, prior to an additional 11-22 infections. CONCLUSIONS: COVID-19 surveillance is challenged by delayed or absent clinical symptoms and imperfect diagnostic sensitivity of standard RT-PCR tests. In our analysis, group testing was the most effective and efficient COVID-19 surveillance strategy for resource-limited LTCFs. Testing cascades were even more effective given ample testing resources. Increasing testing capacity and updating surveillance protocols accordingly could facilitate earlier detection of emerging outbreaks, informing a need for urgent intervention in settings with ongoing nosocomial transmission.

Influenza interaction with cocirculating pathogens and its impact on surveillance, pathogenesis, and epidemic profile: A key role for mathematical modelling.

Evidence is mounting that influenza virus interacts with other pathogens colonising or infecting the human respiratory tract. Taking into account interactions with other pathogens may be critical to determining the real influenza burden and the full impact of public health policies targeting influenza. This is particularly true for mathematical modelling studies, which have become critical in public health decision-making. Yet models usually focus on influenza virus acquisition and infection alone, thereby making broad oversimplifications of pathogen ecology. Herein, we report evidence of influenza virus interactions with bacteria and viruses and systematically review the modelling studies that have incorporated interactions. Despite the many studies examining possible associations between influenza and Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Neisseria meningitidis, respiratory syncytial virus (RSV), human rhinoviruses, human parainfluenza viruses, etc., very few mathematical models have integrated other pathogens alongside influenza. The notable exception is the pneumococcus-influenza interaction, for which several recent modelling studies demonstrate the power of dynamic modelling as an approach to test biological hypotheses on interaction mechanisms and estimate the strength of those interactions. We explore how different interference mechanisms may lead to unexpected incidence trends and possible misinterpretation, and we illustrate the impact of interactions on public health surveillance using simple transmission models. We demonstrate that the development of multipathogen models is essential to assessing the true public health burden of influenza and that it is needed to help improve planning and evaluation of control measures. Finally, we identify the public health, surveillance, modelling, and biological challenges and propose avenues of research for the coming years.

Close proximity interactions support transmission of ESBL-K. pneumoniae but not ESBL-E. coli in healthcare settings.

Antibiotic-resistance of hospital-acquired infections is a major public health issue. The worldwide emergence and diffusion of extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae, including Escherichia coli (ESBL-EC) and Klebsiella pneumoniae (ESBL-KP), is of particular concern. Preventing their nosocomial spread requires understanding their transmission. Using Close Proximity Interactions (CPIs), measured by wearable sensors, and weekly ESBL-EC-and ESBL-KP-carriage data, we traced their possible transmission paths among 329 patients in a 200-bed long-term care facility over 4 months. Based on phenotypically defined resistance profiles to 12 antibiotics only, new bacterial acquisitions were tracked. Extending a previously proposed statistical method, the CPI network's ability to support observed incident-colonization episodes of ESBL-EC and ESBL-KP was tested. Finally, mathematical modeling based on our findings assessed the effect of several infection-control measures. A potential infector was identified in the CPI network for 80% (16/20) of ESBL-KP acquisition episodes. The lengths of CPI paths between ESBL-KP incident cases and their potential infectors were shorter than predicted by chance (P = 0.02), indicating that CPI-network relationships were consistent with dissemination. Potential ESBL-EC infectors were identified for 54% (19/35) of the acquisitions, with longer-than-expected lengths of CPI paths. These contrasting results yielded differing impacts of infection control scenarios, with contact reduction interventions proving less effective for ESBL-EC than for ESBL-KP. These results highlight the widely variable transmission patterns among ESBL-producing Enterobacteriaceae species. CPI networks supported ESBL-KP, but not ESBL-EC spread. These outcomes could help design more specific surveillance and control strategies to prevent in-hospital Enterobacteriaceae dissemination.

Association of Pneumococcal Conjugate Vaccine Coverage With Pneumococcal Meningitis: An Analysis of French Administrative Areas, 2001-2016.

Geographic variations of invasive pneumococcal disease incidence and serotype distributions were observed after pneumococcal conjugate vaccine introduction at regional levels and among French administrative areas. The variations could be related to regional vaccine coverage (VC) variations that might have direct consequences for vaccination-policy impact on invasive pneumococcal disease, particularly pneumococcal meningitis (PM) incidence. We assessed vaccine impact from 2001 to 2016 in France by estimating the contribution of regional VC differences to variations of annual local PM incidence. Using a mixed-effect Poisson model, we showed that, despite some variations of VC among administrative areas, vaccine impact on vaccine-serotype PM was homogeneously confirmed among administrative areas. Compared with the prevaccine era, the cumulative VC impact on vaccine serotypes led, in 2016, to PM reductions ranging among regions from 87% (25th percentile) to 91% (75th percentile) for 7-valent pneumococcal conjugate vaccine serotypes and from 58% to 63% for the 6 additional 13-valent pneumococcal conjugate vaccine serotypes. Nonvaccine-serotype PM increases from the prevaccine era ranged among areas from 98% to 127%. By taking into account the cumulative impact of growing VC and VC differences, our analyses confirmed high vaccine impact on vaccine-serotype PM case rates and suggest that VC variations cannot explain PM administrative area differences.

Characterizing and Comparing the Seasonality of Influenza-Like Illnesses and Invasive Pneumococcal Diseases Using Seasonal Waveforms.

The seasonalities of influenza-like illnesses (ILIs) and invasive pneumococcal diseases (IPDs) remain incompletely understood. Experimental evidence indicates that influenza-virus infection predisposes to pneumococcal disease, so that a correspondence in the seasonal patterns of ILIs and IPDs might exist at the population level. We developed a method to characterize seasonality by means of easily interpretable summary statistics of seasonal shape-or seasonal waveforms. Nonlinear mixed-effects models were used to estimate those waveforms based on weekly case reports of ILIs and IPDs in 5 regions spanning continental France from July 2000 to June 2014. We found high variability of ILI seasonality, with marked fluctuations of peak amplitudes and peak times, but a more conserved epidemic duration. In contrast, IPD seasonality was best modeled by a markedly regular seasonal baseline, punctuated by 2 winter peaks in late December to early January and January to February. Comparing ILI and IPD seasonal waveforms, we found indication of a small, positive correlation. Direct models regressing IPDs on ILIs provided comparable results, even though they estimated moderately larger associations. The method proposed is broadly applicable to diseases with unambiguous seasonality and is well-suited to analyze spatially or temporally grouped data, which are common in epidemiology.