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.

Antimicrobial Resistance as Risk Factor for Recurrent Bacteremia after Staphylococcus aureus, Escherichia coli, or Klebsiella spp. Community-Onset Bacteremia.

We investigated links between antimicrobial resistance in community-onset bacteremia and 1-year bacteremia recurrence by using the clinical data warehouse of Europe's largest university hospital group in France. We included adult patients hospitalized with an incident community-onset Staphylococcus aureus, Escherichia coli, or Klebsiella spp. bacteremia during 2017-2019. We assessed risk factors of 1-year recurrence using Fine-Gray regression models. Of the 3,617 patients included, 291 (8.0%) had >1 recurrence episode. Third-generation cephalosporin (3GC)-resistance was significantly associated with increased recurrence risk after incident Klebsiella spp. (hazard ratio 3.91 [95% CI 2.32-6.59]) or E. coli (hazard ratio 2.35 [95% CI 1.50-3.68]) bacteremia. Methicillin resistance in S. aureus bacteremia had no effect on recurrence risk. Although several underlying conditions and infection sources increased recurrence risk, 3GC-resistant Klebsiella spp. was associated with the greatest increase. These results demonstrate a new facet to illness induced by 3GC-resistant Klebsiella spp. and E. coli in the community setting.

Inappropriate antibiotic prescribing and its determinants among outpatient children in 3 low- and middle-income countries: A multicentric community-based cohort study.

BACKGROUND: Antibiotic resistance is a global public health issue, particularly in low- and middle-income countries (LMICs), where antibiotics required to treat resistant infections are not affordable. LMICs also bear a disproportionately high burden of bacterial diseases, particularly among children, and resistance jeopardizes progress made in these areas. Although outpatient antibiotic use is a major driver of antibiotic resistance, data on inappropriate antibiotic prescribing in LMICs are scarce at the community level, where the majority of prescribing occurs. Here, we aimed to characterize inappropriate antibiotic prescribing among young outpatient children and to identify its determinants in 3 LMICs. METHODS AND FINDINGS: We used data from a prospective, community-based mother-and-child cohort (BIRDY, 2012 to 2018) conducted across urban and rural sites in Madagascar, Senegal, and Cambodia. Children were included at birth and followed-up for 3 to 24 months. Data from all outpatient consultations and antibiotics prescriptions were recorded. We defined inappropriate prescriptions as antibiotics prescribed for a health event determined not to require antibiotic therapy (antibiotic duration, dosage, and formulation were not considered). Antibiotic appropriateness was determined a posteriori using a classification algorithm developed according to international clinical guidelines. We used mixed logistic analyses to investigate risk factors for antibiotic prescription during consultations in which children were determined not to require antibiotics. Among the 2,719 children included in this analysis, there were 11,762 outpatient consultations over the follow-up period, of which 3,448 resulted in antibiotic prescription. Overall, 76.5% of consultations resulting in antibiotic prescription were determined not to require antibiotics, ranging from 71.5% in Madagascar to 83.3% in Cambodia. Among the 10,416 consultations (88.6%) determined not to require antibiotic therapy, 25.3% (n = 2,639) nonetheless resulted in antibiotic prescription. This proportion was much lower in Madagascar (15.6%) than in Cambodia (57.0%) or Senegal (57.2%) (p < 0.001). Among the consultations determined not to require antibiotics, in both Cambodia and Madagascar the diagnoses accounting for the greatest absolute share of inappropriate prescribing were rhinopharyngitis (59.0% of associated consultations in Cambodia, 7.9% in Madagascar) and gastroenteritis without evidence of blood in the stool (61.6% and 24.6%, respectively). In Senegal, uncomplicated bronchiolitis accounted for the greatest number of inappropriate prescriptions (84.4% of associated consultations). Across all inappropriate prescriptions, the most frequently prescribed antibiotic was amoxicillin in Cambodia and Madagascar (42.1% and 29.2%, respectively) and cefixime in Senegal (31.2%). Covariates associated with an increased risk of inappropriate prescription include patient age greater than 3 months (adjusted odds ratios (aOR) with 95% confidence interval (95% CI) ranged across countries from 1.91 [1.63, 2.25] to 5.25 [3.85, 7.15], p < 0.001) and living in rural as opposed to urban settings (aOR ranged across countries from 1.83 [1.57, 2.14] to 4.40 [2.34, 8.28], p < 0.001). Diagnosis with a higher severity score was also associated with an increased risk of inappropriate prescription (aOR = 2.00 [1.75, 2.30] for moderately severe, 3.10 [2.47, 3.91] for most severe, p < 0.001), as was consultation during the rainy season (aOR = 1.32 [1.19, 1.47], p < 0.001). The main limitation of our study is the lack of bacteriological documentation, which may have resulted in some diagnosis misclassification and possible overestimation of inappropriate antibiotic prescription. CONCLUSION: In this study, we observed extensive inappropriate antibiotic prescribing among pediatric outpatients in Madagascar, Senegal, and Cambodia. Despite great intercountry heterogeneity in prescribing practices, we identified common risk factors for inappropriate prescription. This underscores the importance of implementing local programs to optimize antibiotic prescribing at the community level in LMICs.

Short treatment duration for community-acquired pneumonia.

PURPOSE OF REVIEW: Lower respiratory tract infections are one of the most common indications for antibiotic use in community and hospital settings. Usual guidelines for adults with community-acquired pneumonia (CAP) recommend 5-7 days of antibiotic treatment. In daily practice, physicians often prescribe 9-10 days of antibiotic treatment. Among available strategies to decrease antibiotic use, possibly preventing the emergence of bacterial resistance, reducing treatment durations is the safest and the most acceptable to clinicians. We aim to review data evaluating the efficacy of short antibiotic duration in adult CAP and which criteria can help clinicians to reduce antibiotic treatment. RECENT FINDINGS: Several studies and meta-analyses demonstrated that the treatment duration of 7 days or less was sufficient for CAP. Two trials found that 3-day treatments were effective, even in hospitalized CAP.To customize and shorten duration, clinical and biological criteria have been studied and reflect patient's response. Indeed, stability criteria were recently shown to be effective to discontinue antibiotic treatment. Procalcitonin was also studied but never compared with clinical criteria. SUMMARY: Treatment duration for CAP is still under debate, but several studies support short durations. Clinical criteria could be possibly used to discontinue antibiotic treatment.

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.

Incidence and risk factors of neonatal bacterial infections: a community-based cohort from Madagascar (2018-2021).

BACKGROUND: Few studies on neonatal severe bacterial infection are available in LMICs. Data are needed in these countries to prioritize interventions and decrease neonatal infections which are a primary cause of neonatal mortality. The BIRDY project (Bacterial Infections and Antimicrobial Drug Resistant among Young Children) was initially conducted in Madagascar, Senegal and Cambodia (BIRDY 1, 2012-2018), and continued in Madagascar only (BIRDY 2, 2018-2021). We present here the BIRDY 2 project whose objectives were (1) to estimate the incidence of neonatal severe bacterial infections and compare these findings with those obtained in BIRDY 1, (2) to identify determinants associated with severe bacterial infection and (3) to specify the antibiotic resistance pattern of bacteria in newborns. METHODS: The BIRDY 2 study was a prospective community-based mother and child cohort, both in urban and semi-rural areas. All pregnant women in the study areas were identified and enrolled. Their newborns were actively and passively followed-up from birth to 3 months. Data on clinical symptoms developed by the children and laboratory results of all clinical samples investigated were collected. A Cox proportional hazards model was performed to identify risk factors associated with possible severe bacterial infection. FINDINGS: A total of 53 possible severe bacterial infection and 6 confirmed severe bacterial infection episodes were identified among the 511 neonates followed-up, with more than half occurring in the first 3 days. For the first month period, the incidence of confirmed severe bacterial infection was 11.7 per 1,000 live births indicating a 1.3 -fold decrease compared to BIRDY 1 in Madagascar (p = 0.50) and the incidence of possible severe bacterial infection was 76.3, indicating a 2.6-fold decrease compared to BIRDY 1 in Madagascar (p < 0.001). The 6 severe bacterial infection confirmed by blood culture included 5 Enterobacterales and one Enterococcus faecium. The 5 Enterobacterales were extended-spectrum ß-lactamases (ESBL) producers and were resistant to quinolones and gentamicin. Enterococcus faecium was sensitive to vancomycin but resistant to amoxicillin and to gentamicin. These pathogns were classified as multidrug-resistant bacteria and were resistant to antibiotics recommended in WHO guidelines for neonatal sepsis. However, they remained susceptible to carbapenem. Fetid amniotic fluid, need for resuscitation at birth and low birth weight were associated with early onset possible severe bacterial infection. CONCLUSION: Our results suggest that the incidence of severe bacterial infection is still high in the community of Madagascar, even if it seems lower when compared to BIRDY 1 estimates, and that existing neonatal sepsis treatment guidelines may no longer be appropriate in Madagascar. These results motivate to further strengthen actions for the prevention, early diagnosis and case management during the first 3 days of life.

Care pathways of sepsis survivors: sequelae, mortality and use of healthcare services in France, 2015-2018.

BACKGROUND: Individuals who survive sepsis are at high risk of chronic sequelae, resulting in significant health-economic costs. Several studies have focused on aspects of healthcare pathways of sepsis survivors but comprehensive, longitudinal overview of their pathways of care are scarce. The aim of this retrospective, longitudinal cohort study is to identify sepsis survivor profiles based on their healthcare pathways and describe their healthcare consumption and costs over the 3 years following their index hospitalization. METHODS: The data were extracted from the French National Hospital Discharge Database. The study population included all patients above 15 years old, with bacterial sepsis, who survived an incident hospitalization in an acute care facility in 2015. To identify survivor profiles, state sequence and clustering analyses were conducted over the year following the index hospitalization. For each profile, patient characteristics and their index hospital stay and sequelae were described, as well as use of care and its associated monetary costs, both pre- and post-sepsis. RESULTS: New medical (79.2%), psychological (26.9%) and cognitive (18.5%) impairments were identified post-sepsis, and 65.3% of survivors were rehospitalized in acute care. Cumulative mortality reached 36.6% by 3 years post-sepsis. The total medical cost increased by 856 million € in the year post-sepsis. Five patient clusters were identified: home (65.6% of patients), early death (12.9%), late death (6.8%), short-term rehabilitation (11.3%) and long-term rehabilitation (3.3%). Survivors with early and late death clusters had high rates of cancer and primary bacteremia and experienced more hospital-at-home care post-sepsis. Survivors in short- or long-term rehabilitation clusters were older, with higher percentage of septic shock than those coming back home, and had high rates of multiple site infections and higher rates of new psychological and cognitive impairment. CONCLUSIONS: Over three years post-sepsis, different profiles of sepsis survivors were identified with different mortality rates, sequels and healthcare services usage and cost. This study confirmed the importance of sepsis burden and suggests that strategies of post-discharge care, in accordance with patient profile, should be further tested in order to reduce sepsis burden.

Prevalence and factors associated with faecal carriage of extended-spectrum ß-lactamase-producing Enterobacterales among peripartum women in the community in Cambodia.

BACKGROUND: In Southeast-Asia, where many conditions associated with dissemination of ESBL-producing Enterobacterales (ESBL-E) in the community are met, data from the community are scarce but show high ESBL-E carriage prevalence. Maternal ESBL-E colonization is considered a risk factor for neonatal colonization, which is the first step towards developing neonatal sepsis. Despite this, ESBL-E carriage prevalence and its risk factors during pregnancy or postpartum remain undefined in Southeast-Asia. OBJECTIVES: To estimate the prevalence of ESBL-E faecal colonization among peripartum women in the community of an urban and a rural area in Cambodia, to investigate ESBL-E genomic characteristics and to identify associated risk factors. METHODS: Epidemiological data and faecal samples from 423 peripartum women were collected in an urban and rural areas in Cambodia (2015-16). Bacterial cultures, antibiotic susceptibility tests and ESBL gene sequencing were performed. Risk factor analysis was conducted using logistic regression. RESULTS: The prevalence of ESBL-E faecal carriage was 79.2% (95% CI 75.0%-82.8%) among which Escherichia coli (n = 315/335, 94.0%) were most frequent. All isolates were multidrug resistant. Among 318 ESBL-E, the genes most frequently detected were blaCTX-M-15 (41.5%), blaCTX-M-55 (24.8%), and blaCTX-M-27 (15.1%). Low income, undernutrition, multiparity, regular consumption of pork, dried meat, and raw vegetables, were associated with ESBL-E faecal carriage. CONCLUSIONS: The high prevalence of ESBL-E carriage observed among peripartum women in Southeast-Asia and the identified associated factors underline the urgent need for public health measures to address antimicrobial resistance, including a 'One Health' approach.

One-year hospital readmission for recurrent sepsis: associated risk factors and impact on 1-year mortality-a French nationwide study.

BACKGROUND: Sepsis is a complex health condition, leading to long-term morbidity and mortality. Understanding the risk factors for recurrent sepsis, as well as its impact on mid- and long-term mortality among other risk factors, is essential to improve patient survival. METHODS: A risk factor analysis, based on French nationwide medico-administrative data, was conducted on a cohort of patients above 15 years old, hospitalized with an incident sepsis in metropolitan France between 1st January 2018 and 31st December 2018 and who survived their index hospitalization. Two main analyses, focusing on outcomes occurring 1-year post-discharge, were conducted: a first one to assess risk factors for recurrent sepsis and a second to assess risk factors for mortality. RESULTS: Of the 178017 patients surviving an incident sepsis episode in 2018 and included in this study, 22.3% died during the 1-year period from discharge and 73.8% had at least one hospital readmission in acute care, among which 18.1% were associated with recurrent sepsis. Patients aged between 56 and 75, patients with cancer and renal disease, with a long index hospital stay or with mediastinal or cardiac infection had the highest odds of recurrent sepsis. One-year mortality was higher for patients with hospital readmission for recurrent sepsis (aOR 2.93; 99% CI 2.78-3.09). Among all comorbidities, patients with cancer (aOR 4.35; 99% CI 4.19-4.52) and dementia (aOR 2.02; 99% CI 1.90-2.15) had the highest odds of 1-year mortality. CONCLUSION: Hospital readmission for recurrent sepsis is one of the most important risk factors for 1-year mortality of septic patients, along with age and comorbidities. Our study suggests that recurrent sepsis, as well as modifiable or non-modifiable other risk factors identified, should be considered in order to improve patient care pathway and survival.

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.

Severe bacterial neonatal infections in Madagascar, Senegal, and Cambodia: A multicentric community-based cohort study.

BACKGROUND: Severe bacterial infections (SBIs) are a leading cause of neonatal deaths in low- and middle-income countries (LMICs). However, most data came from hospitals, which do not include neonates who did not seek care or were treated outside the hospital. Studies from the community are scarce, and few among those available were conducted with high-quality microbiological techniques. The burden of SBI at the community level is therefore largely unknown. We aimed here to describe the incidence, etiology, risk factors, and antibiotic resistance profiles of community-acquired neonatal SBI in 3 LMICs. METHODS AND FINDINGS: The BIRDY study is a prospective multicentric community-based mother and child cohort study and was conducted in both urban and rural areas in Madagascar (2012 to 2018), Cambodia (2014 to 2018), and Senegal (2014 to 2018). All pregnant women within a geographically defined population were identified and enrolled. Their neonates were actively followed from birth to 28 days to document all episodes of SBI. A total of 3,858 pregnant women (2,273 (58.9%) in Madagascar, 814 (21.1%) in Cambodia, and 771 (20.0%) in Senegal) were enrolled in the study, and, of these, 31.2% were primigravidae. Women enrolled in the urban sites represented 39.6% (900/2,273), 45.5% (370/814), and 61.9% (477/771), and those enrolled in the rural sites represented 60.4% (1,373/2,273), 54.5% (444/814), and 38.1% (294/771) of the total in Madagascar, Cambodia, and Senegal, respectively. Among the 3,688 recruited newborns, 49.6% were male and 8.7% were low birth weight (LBW). The incidence of possible severe bacterial infection (pSBI; clinical diagnosis based on WHO guidelines of the Integrated Management of Childhood Illness) was 196.3 [95% confidence interval (CI) 176.5 to 218.2], 110.1 [88.3 to 137.3], and 78.3 [59.5 to 103] per 1,000 live births in Madagascar, Cambodia, and Senegal, respectively. The incidence of pSBI differed between urban and rural sites in all study countries. In Madagascar, we estimated an incidence of 161.0 pSBI per 1,000 live births [133.5 to 194] in the urban site and 219.0 [192.6 to 249.1] pSBI per 1,000 live births in the rural site (p = 0.008). In Cambodia, estimated incidences were 141.1 [105.4 to 189.0] and 85.3 [61.0 to 119.4] pSBI per 1,000 live births in urban and rural sites, respectively (p = 0.025), while in Senegal, we estimated 103.6 [76.0 to 141.2] pSBI and 41.5 [23.0 to 75.0] pSBI per 1,000 live births in urban and rural sites, respectively (p = 0.006). The incidences of culture-confirmed SBI were 15.2 [10.6 to 21.8], 6.5 [2.7 to 15.6], and 10.2 [4.8 to 21.3] per 1,000 live births in Madagascar, Cambodia, and Senegal, respectively, with no difference between urban and rural sites in each country. The great majority of early-onset infections occurred during the first 3 days of life (72.7%). The 3 main pathogens isolated were Klebsiella spp. (11/45, 24.4%), Escherichia coli (10/45, 22.2%), and Staphylococcus spp. (11/45, 24.4%). Among the 13 gram-positive isolates, 5 were resistant to gentamicin, and, among the 29 gram-negative isolates, 13 were resistant to gentamicin, with only 1 E. coli out of 10 sensitive to ampicillin. Almost one-third of the isolates were resistant to both first-line drugs recommended for the management of neonatal sepsis (ampicillin and gentamicin). Overall, 38 deaths occurred among neonates with SBI (possible and culture-confirmed SBI together). LBW and foul-smelling amniotic fluid at delivery were common risk factors for early pSBI in all 3 countries. A main limitation of the study was the lack of samples from a significant proportion of infants with pBSI including 35 neonatal deaths. Without these samples, bacterial infection and resistance profiles could not be confirmed. CONCLUSIONS: In this study, we observed a high incidence of neonatal SBI, particularly in the first 3 days of life, in the community of 3 LMICs. The current treatment for the management of neonatal infection is hindered by antimicrobial resistance. Our findings suggest that microbiological diagnosis of SBI remains a challenge in these settings and support more research on causes of neonatal death and the implementation of early interventions (e.g., follow-up of at-risk newborns during the first days of life) to decrease the burden of neonatal SBI and associated mortality and help achieve Sustainable Development Goal 3.

Antibiotic prescriptions and risk factors for antimicrobial resistance in patients hospitalized with urinary tract infection: a matched case-control study using the French health insurance database (SNDS).

BACKGROUND: Antibiotic resistance is increasing among urinary pathogens, resulting in worse clinical and economic outcomes. We analysed factors associated with antibiotic-resistant bacteria (ARB) in patients hospitalized for urinary tract infection, using the comprehensive French national claims database. METHODS: Hospitalized urinary tract infections were identified from 2015 to 2017. Cases (due to ARB) were matched to controls (without ARB) according to year, age, sex, infection, and bacterium. Healthcare-associated (HCAI) and community-acquired (CAI) infections were analysed separately; logistic regressions were stratified by sex. RESULTS: From 9460 cases identified, 6468 CAIs and 2855 HCAIs were matched with controls. Over a 12-months window, the risk increased when exposure occurred within the last 3 months. The following risk factors were identified: antibiotic exposure, with an OR reaching 3.6 [2.8-4.5] for men with CAI, mostly associated with broad-spectrum antibiotics; surgical procedure on urinary tract (OR 2.0 [1.5-2.6] for women with HCAI and 1.3 [1.1-1.6] for men with CAI); stay in intensive care unit > 7 days (OR 1.7 [1.2-2.6] for men with HCAI). Studied co-morbidities had no impact on ARB. CONCLUSIONS: This study points out the critical window of 3 months for antibiotic exposure, confirms the impact of broad-spectrum antibiotic consumption on ARB, and supports the importance of prevention during urological procedures, and long intensive care unit stays.

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.

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.

Characterization of Klebsiella pneumoniae isolates from a mother-child cohort in Madagascar.

OBJECTIVES: To define characteristics of Klebsiella pneumoniae isolated from carriage and infections in mothers and their neonates belonging to a paediatric cohort in Madagascar. METHODS: A total of 2000 mothers and their 2001 neonates were included. For each mother, vaginal and stool samples were collected at the birth. Additionally, upon suspicion of infection, samples were collected from suspected infected body sites in 121 neonates. Genomic sequences of all isolated K. pneumoniae were used for phylogenetic analyses and to investigate the genomic content of antimicrobial resistance genes, virulence genes and plasmid replicon types. RESULTS: Five percent (n = 101) of mothers were K. pneumoniae positive. Of 251 collected K. pneumoniae isolates, 102 (40.6%) were from mothers and 149 (59.3%) were from neonates. A total of 49 (19.5%; all from infants except 1) isolates were from infected body sites. MLST identified 108 different STs distributed over the six K. pneumoniae phylogroups Kp1 to Kp6. We found 65 (25.8%) ESBL producers and a total of 101 (40.2%) MDR isolates. The most common ESBL gene was blaCTX-M-15 (in 99.3% of isolates expressing ESBL). One isolate co-harboured blaCTX-M-15 and blaNDM-1 genes. Three isolates from infected body sites belonged to hypervirulent-associated ST23 (n = 1) and ST25 (n = 2). We observed two cases of mother-to-child transmission and sustained K. pneumoniae carriage was identified in 10 neonates, with identical isolates observed longitudinally over the course of 18 to 115 days. CONCLUSIONS: This study revealed substantial genetic diversity and a high rate of antimicrobial resistance among K. pneumoniae isolated from both carriage and infections in Madagascar.

Host contact dynamics shapes richness and dominance of pathogen strains.

The interaction among multiple microbial strains affects the spread of infectious diseases and the efficacy of interventions. Genomic tools have made it increasingly easy to observe pathogenic strains diversity, but the best interpretation of such diversity has remained difficult because of relationships with host and environmental factors. Here, we focus on host-to-host contact behavior and study how it changes populations of pathogens in a minimal model of multi-strain interaction. We simulated a population of identical strains competing by mutual exclusion and spreading on a dynamical network of hosts according to a stochastic susceptible-infectious-susceptible model. We computed ecological indicators of diversity and dominance in strain populations for a collection of networks illustrating various properties found in real-world examples. Heterogeneities in the number of contacts among hosts were found to reduce diversity and increase dominance by making the repartition of strains among infected hosts more uneven, while strong community structure among hosts increased strain diversity. We found that the introduction of strains associated with hosts entering and leaving the system led to the highest pathogenic richness at intermediate turnover levels. These results were finally illustrated using the spread of Staphylococcus aureus in a long-term health-care facility where close proximity interactions and strain carriage were collected simultaneously. We found that network structural and temporal properties could account for a large part of the variability observed in strain diversity. These results show how stochasticity and network structure affect the population ecology of pathogens and warn against interpreting observations as unambiguous evidence of epidemiological differences between strains.

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.

Meat and Fish as Sources of Extended-Spectrum ß-Lactamase-Producing Escherichia coli, Cambodia.

We compared extended-spectrum ß-lactamase-producing Escherichia coli isolates from meat and fish, gut-colonized women, and infected patients in Cambodia. Nearly half of isolates from women were phylogenetically related to food-origin isolates; a subset had identical multilocus sequence types, extended-spectrum ß-lactamase types, and antimicrobial resistance patterns. Eating sun-dried poultry may be an exposure route.

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.