Viral genomic features predict orthopoxvirus reservoir hosts.

Orthopoxviruses (OPVs), including the causative agents of smallpox and mpox have led to devastating outbreaks in human populations worldwide. However, the discontinuation of smallpox vaccination, which also provides cross-protection against related OPVs, has diminished global immunity to OPVs more broadly. We apply machine learning models incorporating both host ecological and viral genomic features to predict likely reservoirs of OPVs. We demonstrate that incorporating viral genomic features in addition to host ecological traits enhanced the accuracy of potential OPV host predictions, highlighting the importance of host-virus molecular interactions in predicting potential host species. We identify hotspots for geographic regions rich with potential OPV hosts in parts of southeast Asia, equatorial Africa, and the Amazon, revealing high overlap between regions predicted to have a high number of potential OPV host species and those with the lowest smallpox vaccination coverage, indicating a heightened risk for the emergence or establishment of zoonotic OPVs. Our findings can be used to target wildlife surveillance, particularly related to concerns about mpox establishment beyond its historical range.

Cost-effectiveness of carbapenem-resistant Enterobacteriaceae (CRE) surveillance in Maryland.

OBJECTIVE: We analyzed the efficacy, cost, and cost-effectiveness of predictive decision-support systems based on surveillance interventions to reduce the spread of carbapenem-resistant Enterobacteriaceae (CRE). DESIGN: We developed a computational model that included patient movement between acute-care hospitals (ACHs), long-term care facilities (LTCFs), and communities to simulate the transmission and epidemiology of CRE. A comparative cost-effectiveness analysis was conducted on several surveillance strategies to detect asymptomatic CRE colonization, which included screening in ICUs at select or all hospitals, a statewide registry, or a combination of hospital screening and a statewide registry. SETTING: We investigated 51 ACHs, 222 LTCFs, and skilled nursing facilities, and 464 ZIP codes in the state of Maryland. PATIENTS OR PARTICIPANTS: The model was informed using 2013-2016 patient-mix data from the Maryland Health Services Cost Review Commission. This model included all patients that were admitted to an ACH. RESULTS: On average, the implementation of a statewide CRE registry reduced annual CRE infections by 6.3% (18.8 cases). Policies of screening in select or all ICUs without a statewide registry had no significant impact on the incidence of CRE infections. Predictive algorithms, which identified any high-risk patient, reduced colonization incidence by an average of 1.2% (3.7 cases) without a registry and 7.0% (20.9 cases) with a registry. Implementation of the registry was estimated to save $572,000 statewide in averted infections per year. CONCLUSIONS: Although hospital-level surveillance provided minimal reductions in CRE infections, regional coordination with a statewide registry of CRE patients reduced infections and was cost-effective.

Modelling COVID-19 transmission in Africa: countrywise projections of total and severe infections under different lockdown scenarios.

OBJECTIVES: As of 13 January 2021, there have been 3 113 963 confirmed cases of SARS-CoV-2 and 74 619 deaths across the African continent. Despite relatively lower numbers of cases initially, many African countries are now experiencing an exponential increase in case numbers. Estimates of the progression of disease and potential impact of different interventions are needed to inform policymaking decisions. Herein, we model the possible trajectory of SARS-CoV-2 in 52 African countries under different intervention scenarios. DESIGN: We developed a compartmental model of SARS-CoV-2 transmission to estimate the COVID-19 case burden for all African countries while considering four scenarios: no intervention, moderate lockdown, hard lockdown and hard lockdown with continued restrictions once lockdown is lifted. We further analysed the potential impact of COVID-19 on vulnerable populations affected by HIV/AIDS and tuberculosis (TB). RESULTS: In the absence of an intervention, the most populous countries had the highest peaks in active projected number of infections with Nigeria having an estimated 645 081 severe infections. The scenario with a hard lockdown and continued post-lockdown interventions to reduce transmission was the most efficacious strategy for delaying the time to the peak and reducing the number of cases. In South Africa, projected peak severe infections increase from 162 977 to 2 03 261, when vulnerable populations with HIV/AIDS and TB are included in the analysis. CONCLUSION: The COVID-19 pandemic is rapidly spreading across the African continent. Estimates of the potential impact of interventions and burden of disease are essential for policymakers to make evidence-based decisions on the distribution of limited resources and to balance the economic costs of interventions with the potential for saving lives.

Assessment of WHO antibiotic consumption and access targets in 76 countries, 2000-15: an analysis of pharmaceutical sales data.

BACKGROUND: The WHO Access, Watch, and Reserve (AWaRe) antibiotic classification framework aims to balance appropriate access to antibiotics and stewardship. We aimed to identify how patterns of antibiotic consumption in each of the AWaRe categories changed across countries over 15 years. METHODS: Antibiotic consumption was classified into Access, Watch, and Reserve categories for 76 countries between 2000, and 2015, using quarterly national sample survey data obtained from IQVIA. We measured the proportion of antibiotic use in each category, and calculated the ratio of Access antibiotics to Watch antibiotics (access-to-watch index), for each country. FINDINGS: Between 2000, and 2015, global per-capita consumption of Watch antibiotics increased by 90·9% (from 3·3 to 6·3 defined daily doses per 1000 inhabitants per day [DIDs]) compared with an increase of 26·2% (from 8·4 to 10·6 DIDs) in Access antibiotics. The increase in Watch antibiotic consumption was greater in low-income and middle-income countries (LMICs; 165·0%; from 2·0 to 5·3 DIDs) than in high-income countries (HICs; 27·9%; from 6·1 to 7·8 DIDs). The access-to-watch index decreased by 38·5% over the study period globally (from 2·6 to 1·6); 46·7% decrease in LMICs (from 3·0 to 1·6) and 16·7% decrease in HICs (from 1·8 to 1·5), and 37 (90%) of 41 LMICs had a decrease in their relative access-to-watch consumption. The proportion of countries in which Access antibiotics represented at least 60% of their total antibiotic consumption (the WHO national-level target) decreased from 50 (76%) of 66 countries in 2000, to 42 (55%) of 76 countries in 2015. INTERPRETATION: Rapid increases in Watch antibiotic consumption, particularly in LMICs, reflect challenges in antibiotic stewardship. Without policy changes, the WHO national-level target of at least 60% of total antibiotic consumption being in the Access category by 2023, will be difficult to achieve. The AWaRe framework is an important measure of the effort to combat antimicrobial resistance and to ensure equal access to effective antibiotics between countries. FUNDING: US Centers for Disease Control and Prevention.

Estimating the cost of interventions to improve water, sanitation and hygiene in healthcare facilities across India.

INTRODUCTION: Despite increasing utilisation of institutional healthcare in India, many healthcare facilities (HCFs) lack access to basic water, sanitation and hygiene (WASH) services. WASH services protect patients by improving infection prevention and control (IPC), which in turn can reduce the burden of healthcare-associated infections (HAIs). However, data on the cost of implementing WASH interventions in Indian HCFs are limited. METHODS: We surveyed 32 HCFs across India, varying in size, type and setting to obtain the direct costs of providing improved water supply, sanitation and IPC-supporting infrastructure. We calculated the average costs of WASH interventions and the number of HCFs nationwide requiring investments in WASH to estimate the financial cost of improving WASH across India's public healthcare system over 1 year. RESULTS: Improving WASH across India's public healthcare sector and sustaining services among upgraded facilities for 1 year would cost US$354 million in capital costs and US$289 million in recurrent costs from the provider perspective. The most costly interventions were those on water (US$238 million), linen reprocessing (US$112 million) and sanitation (US$104 million), while the least costly were interventions on hand hygiene (US$52 million), medical device reprocessing (US$56 million) and environmental surface cleaning (US$80 million). Overall, investments in rural HCFs would account for 64.4% of total costs, of which 52.3% would go towards primary health centres. CONCLUSION: Improving IPC in Indian public HCFs can aid in the prevention of HAIs to reduce the spread of antimicrobial resistance. Although WASH is a necessary component of IPC, coverage remains low in HCFs in India. Using ex-post costs, our results estimate the investment levels needed to improve WASH across the Indian public healthcare system and provide a basis for policymakers to support IPC-related National Action Plan activities for antimicrobial resistance through investments in WASH.

The Impact of Influenza Vaccination on Antibiotic Use in the United States, 2010-2017.

BACKGROUND: Influenza, which peaks seasonally, is an important driver for antibiotic prescribing. Although influenza vaccination has been shown to reduce severe illness, evidence of the population-level effects of vaccination coverage on rates of antibiotic prescribing in the United States is lacking. METHODS: We conducted a retrospective analysis of influenza vaccination coverage and antibiotic prescribing rates from 2010 to 2017 across states in the United States, controlling for differences in health infrastructure and yearly vaccine effectiveness. Using data from IQVIA's Xponent database and the US Centers for Disease Control and Prevention's FluVaxView, we employed fixed-effects regression analysis to analyze the relationship between influenza vaccine coverage rates and the number of antibiotic prescriptions per 1000 residents from January to March of each year. RESULTS: We observed that, controlling for socioeconomic differences, access to health care, childcare centers, climate, vaccine effectiveness, and state-level differences, a 10-percentage point increase in the influenza vaccination rate was associated with a 6.5% decrease in antibiotic use, equivalent to 14.2 (95% CI, 6.0-22.4; P = .001) fewer antibiotic prescriptions per 1000 individuals. Increased vaccination coverage reduced prescribing rates the most in the pediatric population (0-18 years), by 15.2 (95% CI, 9.0-21.3; P < .001) or 6.0%, and the elderly (aged 65+), by 12.8 (95% CI, 6.5-19.2; P < .001) or 5.2%. CONCLUSIONS: Increased influenza vaccination uptake at the population level is associated with state-level reductions in antibiotic use. Expanding influenza vaccination could be an important intervention to reduce unnecessary antibiotic prescribing.

The Role of Healthcare Worker-Mediated Contact Networks in the Transmission of Vancomycin-Resistant Enterococci.

BACKGROUND: User- and time-stamped data from hospital electronic health records (EHRs) present opportunities to evaluate how healthcare worker (HCW)-mediated contact networks impact transmission of multidrug-resistant pathogens, such as vancomycin-resistant enterococci (VRE). METHODS: This is a retrospective analysis of incident acquisitions of VRE between July 1, 2016 and June 30, 2018. Clinical and demographic patient data were extracted from the hospital EHR system, including all recorded HCW contacts with patients. Contacts by an HCW with 2 different patients within 1 hour was considered a "connection". Incident VRE acquisition was determined by positive clinical or surveillance cultures collected ≥72 hours after a negative surveillance culture. RESULTS: There were 2952 hospitalizations by 2364 patients who had ≥2 VRE surveillance swabs, 112 (4.7%) patients of which had incident nosocomial acquisitions. Patients had a median of 24 (interquartile range [IQR], 18-33) recorded HCW contacts per day, 9 (IQR, 5-16) of which, or approximately 40%, were connections that occurred <1 hour after another patient contact. Patients that acquired VRE had a higher average number of daily connections to VRE-positive patients (3.1 [standard deviation {SD}, 2.4] versus 2.0 [SD, 2.1]). Controlling for other risk factors, connection to a VRE-positive patient was associated with increased odds of acquiring VRE (odds ratio, 1.64; 95% confidence interval, 1.39-1.92). CONCLUSIONS: We demonstrated that EHR data can be used to quantify the impact of HCW-mediated patient connections on transmission of VRE in the hospital. Defining incident acquisition risk of multidrug-resistant organisms through HCWs connections from EHR data in real-time may aid implementation and evaluation of interventions to contain their spread.

Tracking global trends in the effectiveness of antibiotic therapy using the Drug Resistance Index.

BACKGROUND: Evaluating trends in antibiotic resistance and communicating the results to a broad audience are important for dealing with this global threat. The Drug Resistance Index (DRI), which combines use and resistance into a single measure, was developed as an easy-to-understand measure of the effectiveness of antibiotic therapy. We demonstrate its utility in communicating differences in the effectiveness of antibiotic therapy across countries. METHODS: We calculated the DRI for countries with data on antibiotic use and resistance for the disease-causing organisms considered by the WHO as priority pathogens: Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, Enterococcus faecium and Enterococcus faecalis. Additionally, we estimated pooled worldwide resistance rates for these pathogens. RESULTS: 41 countries had the requisite data and were included in the study. Resistance and use rates were highly variable across countries, but A. baumannii resistance rates were uniformly higher, on average, than other organisms. High-income countries, particularly Sweden, Canada, Norway, Finland and Denmark, had the lowest DRIs; the countries with the highest DRIs, and therefore the lowest effectiveness of antibiotic therapy, were all low-income and middle-income countries. CONCLUSIONS: The DRI is a useful indicator of the problem of resistance. By combining data on antibiotic use with resistance, it captures a snapshot of how the antibiotics a country typically uses match their resistance profiles. This single measure of the effectiveness of antibiotic therapy provides a means of benchmarking against other countries and can, over time, indicate changes in drug effectiveness that can be easily communicated.

The Mortality Burden of Multidrug-resistant Pathogens in India: A Retrospective, Observational Study.

BACKGROUND: The threat posed by antibiotic resistance is of increasing concern in low- and middle-income countries (LMICs) as their rates of antibiotic use increase. However, an understanding of the burden of resistance is lacking in LMICs, particularly for multidrug-resistant (MDR) pathogens. METHODS: We conducted a retrospective, 10-hospital study of the relationship between MDR pathogens and mortality in India. Patient-level antimicrobial susceptibility test (AST) results for Enterococcus spp., Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. were analyzed for their association with patient mortality outcomes. RESULTS: We analyzed data on 5103 AST results from 10 hospitals. The overall mortality rate of patients was 13.1% (n = 581), and there was a significant relationship between MDR and mortality. Infections with MDR and extensively drug resistant (XDR) E. coli, XDR K. pneumoniae, and MDR A. baumannii were associated with 2-3 times higher mortality. Mortality due to methicillin-resistant S. aureus (MRSA) was significantly higher than susceptible strains when the MRSA isolate was resistant to aminoglycosides. CONCLUSIONS: This is one of the largest studies undertaken in an LMIC to measure the burden of antibiotic resistance. We found that MDR bacterial infections pose a significant risk to patients. While consistent with prior studies, the variations in drug resistance and associated mortality outcomes by pathogen are different from those observed in high-income countries and provide a baseline for studies in other LMICs. Future research should aim to elucidate the burden of resistance and the differential transmission mechanisms that drive this public health crisis.

National Costs Associated With Methicillin-Susceptible and Methicillin-Resistant Staphylococcus aureus Hospitalizations in the United States, 2010-2014.

Background: Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) have been associated with worse patient outcomes and higher costs of care than methicillin-susceptible (MSSA) infections. However, since prior studies found these differences, the healthcare landscape has changed, including widespread dissemination of community-associated strains of MRSA. We sought to provide updated estimates of the excess costs of MRSA infections. Methods: We conducted a retrospective analysis using data from the National Inpatient Sample from the Agency for Healthcare Research and Quality for the years 2010-2014. We calculated costs for hospitalizations, including MRSA- and MSSA-related septicemia and pneumonia infections, as well as MRSA- and MSSA-related infections from conditions classified elsewhere and of an unspecified site ("other infections"). Differences in the costs of hospitalization were estimated using propensity score-adjusted mortality outcomes for 2010-2014. Results: In 2014, estimated costs were highest for pneumonia and sepsis-related hospitalizations. Propensity score-adjusted costs were significantly higher for MSSA-related pneumonia ($40725 vs $38561; P = .045) and other hospitalizations ($15578 vs $14792; P < .001) than for MRSA-related hospitalizations. Similar patterns were observed from 2010 to 2013, although crude cost differences between MSSA- and MRSA-related pneumonia hospitalizations rose from 25.8% in 2010 to 31.0% in 2014. Compared with MSSA-related hospitalizations, MRSA-related hospitalizations had a higher adjusted mortality rate. Conclusions: Although MRSA infections had been previously associated with higher hospitalization costs, our results suggest that, in recent years, costs associated with MSSA-related infections have converged with and may surpass costs of similar MRSA-related hospitalizations.

Parental Psychological Distress and Family Food Insecurity: Sad Dads in Hungry Homes.

OBJECTIVE: To examine whether household food insecurity is associated with serious psychological distress (SPD) in fathers and mothers in a nationally representative US sample. METHODS: We analyzed cross-sectional, matched child-parent data from the 2014 to 2015 National Health Interview Survey (N = 18,456). Parental psychological distress was assessed using the Kessler-6 (K-6) scale. Family food security was measured using the USDA's 10-item Food Security scale, and households were dichotomized as food secure or food insecure. Multivariate logistic regression analyses were performed to examine associations between SPD and food insecurity stratified by parental status (mother/father), controlling for sociodemographic factors. RESULTS: One hundred forty-seven (2.0%) fathers, 444 (3.9%) mothers, and 591 (3.2%) of all parents had K-6 scores indicating SPD. A total of 2414 (13.1%) parents reported being food insecure, including 750 (10.4%) fathers and 1664 (14.8%) mothers. In multivariate analyses, food insecurity was significantly associated with SPD both among fathers and mothers (odds ratio [OR] = 4.2; 95% confidence interval [CI], 2.4-7.3 and OR = 2.6; 95% CI, 1.9-3.5, respectively). CONCLUSION: This is the first study we are aware of to demonstrate that food insecurity is independently associated with SPD among fathers and mothers, and that fathers may be at higher risk of SPD than mothers in food insecure homes. These findings highlight the need to assess and treat the mental health of fathers, a historically underrepresented group in the fields of mental health and pediatrics, in addition to mothers, in food insecure homes.