Widespread interspecific phylogenetic tree incongruence between mosquito-borne and insect-specific flaviviruses at hotspots originally identified in Zika virus.

Intraspecies (homologous) phylogenetic incongruence, or 'tree conflict' between different loci within the same genome of mosquito-borne flaviviruses (MBFV), was first identified in dengue virus (DENV) and subsequently in Japanese encephalitis virus (JEV), St Louis encephalitis virus, and Zika virus (ZIKV). Recently, the first evidence of phylogenetic incongruence between interspecific members of the MBFV was reported in ZIKV and its close relative, Spondweni virus. Uniquely, these hybrid proteomes were derived from four incongruent trees involving an Aedes-associated DENV node (1 tree) and three different Culex-associated flavivirus nodes (3 trees). This analysis has now been extended across a wider spectrum of viruses within the MBFV lineage targeting the breakpoints between phylogenetic incongruent loci originally identified in ZIKV. Interspecies phylogenetic incongruence at these breakpoints was identified in 10 of 50 viruses within the MBFV lineage, representing emergent Aedes and Culex-associated viruses including JEV, West Nile virus, yellow fever virus, and insect-specific viruses. Thus, interspecies phylogenetic incongruence is widespread amongst the flaviviruses and is robustly associated with the specific breakpoints that coincide with the interspecific phylogenetic incongruence previously identified, inferring they are 'hotspots'. The incongruence amongst the emergent MBFV group was restricted to viruses within their respective associated epidemiological boundaries. This MBFV group was RY-coded at the third codon position ('wobble codon') to remove transition saturation. The resulting 'wobble codon' trees presented a single topology for the entire genome that lacked any robust evidence of phylogenetic incongruence between loci. Phylogenetic interspecific incongruence was therefore observed for exactly the same loci between amino acid and the RY-coded 'wobble codon' alignments and this incongruence represented either a major part, or the entire genomes. Maximum likelihood codon analysis revealed positive selection for the incongruent lineages. Positive selection could result in the same locus producing two opposing trees. These analyses for the clinically important MBFV suggest that robust interspecific phylogenetic incongruence resulted from amino acid selection. Convergent or parallel evolutions are evolutionary processes that would explain the observation, whilst interspecific recombination is unlikely.

The Berrettini palmar neural communicating branch: a study of 27 cadaveric specimens and determination of a high-risk surgical zone.

In this cadaveric study, we analysed digital images of dissected palms to define the location and length of superficial connections between the median and the ulnar nerves (Berrettini communicating branches). We found the connections present in 12 of 27 hands. We used a coordinate model to define their location relative to seven specified landmarks. The model revealed that the Berrettini communicating branches were positioned consistently, and we defined a high-risk zone in the palm that fully contained seven of the 12 connections, while others had minor projections outside the zone. We conclude that awareness of this high-risk zone in the palm can be of some help to reduce the risk of iatrogenic nerve injury, however, any operation in the palm must always be done with great care to visualize and protect any possible anatomically unusual structures.

Tracing and tracking the emergence, epidemiology and dispersal of dengue virus to Africa during the 20th century.

The four mosquito-borne dengue virus serotypes (DENV1-DENV4) cause a high burden of disease throughout the tropical and sub-tropical regions of the world. Nevertheless, their precise epidemiological history in Africa, including when and where they originated and were distributed during the 20th century, remains unclear stressing the need for One Health focused research. Accordingly, we conducted a time-scaled molecular epidemiological reconstruction using publicly available and newly sequenced dengue virus genomes of African origin representing all four serotypes to deduce the most likely temporal and spatial transmission routes of each DENV serotype from their ancestral regions to, within and from Africa. Our analyses suggest that during the 20th century, serotypes DENV1-DENV3 were introduced to Africa from South East Asia on multiple occasions. The earliest evidence recorded indicates introduction of DENV2 during the early-1940s and of DENV1 during the mid-1940s to Western Africa from South East Asia. The analysis also implies an early introduction of DENV4 during the mid-1940s to Western Africa, alongside DENV1, probably originating in South East Asia. Establishment of DENV3 in Africa appears to have occurred later in the 1960s, apparently originating from South East Asia. However, with the re-establishment of DENV in the Americas, following the cessation of the PAHO mosquito control programme during the mid-20th century, evidence of introductions of DENV1 and DENV2 from the Americas to Western Africa was also observed. The data also identify intra-regional circulation of DENV, but also inter-regional dispersal of all four serotypes within Africa, which has led to a high degree of geographical overlap among serotypes. It is also noteworthy that DENV from both Eastern and Western Africa, have been introduced into Central Africa but there is no support for the converse relationship. For serotypes DENV1-DENV3, we observed probable exports from within established African DENV clusters (≥2 sequences) primarily to Eastern and Southern Asia. Collectively, our findings support the view that all DENV serotypes, apart from DENV4, have been introduced on multiple occasions to Africa, primarily originating from South East Asia, and subsequently to neighbouring regions within Africa.

Recombination of B- and T-cell epitope-rich loci from Aedes- and Culex-borne flaviviruses shapes Zika virus epidemiology.

Sporadic human Zika virus (ZIKV) infections have been recorded in Africa and Asia since the 1950s. Major epidemics occurred only after ZIKV emerged in the Pacific islands and spread to the Americas. Specific biological determinants of the explosive epidemic nature of ZIKV have not been identified. Phylogenetic studies revealed incongruence in ZIKV placement in relation to Aedes-borne dengue viruses (DENV) and Culex-borne flaviviruses. We hypothesized that this incongruence reflects interspecies recombination resulting in ZIKV evasion of cross-protective T-cell immunity. We investigated ZIKV phylogenetic incongruence in relation to: DENV T-cell epitope maps experimentally identified ex vivo, published B-cell epitope loci, and CD8+ T-cell epitopes predicted in silico for mosquito-borne flaviviruses. Our findings demonstrate that the ZIKV proteome is a hybrid of Aedes-borne DENV proteins interspersed amongst Culex-borne flavivirus proteins derived through independent interspecies recombination events. These analyses infer that DENV-associated proteins in the ZIKV hybrid proteome generated immunodominant human B-cell responses, whereas ZIKV recombinant derived Culex-borne flavivirus-associated proteins generated immunodominant CD8+ and/or CD4+ T-cell responses. In silico CD8+ T-cell epitope ZIKV cross-reactive prediction analyses verified this observation. We propose that by acquiring cytotoxic T-cell epitope-rich regions from Culex-borne flaviviruses, ZIKV evaded DENV-generated T-cell immune cross-protection. Thus, Culex-borne flaviviruses, including West Nile virus and Japanese encephalitis virus, might induce cross-protective T-cell responses against ZIKV. This would explain why explosive ZIKV epidemics occurred in DENV-endemic regions of Micronesia, Polynesia and the Americas where Culex-borne flavivirus outbreaks are infrequent and why ZIKV did not cause major epidemics in Asia where Culex-borne flaviviruses are widespread.

ZikaPLAN: addressing the knowledge gaps and working towards a research preparedness network in the Americas.

Zika Preparedness Latin American Network (ZikaPLAN) is a research consortium funded by the European Commission to address the research gaps in combating Zika and to establish a sustainable network with research capacity building in the Americas. Here we present a report on ZikaPLAN`s mid-term achievements since its initiation in October 2016 to June 2019, illustrating the research objectives of the 15 work packages ranging from virology, diagnostics, entomology and vector control, modelling to clinical cohort studies in pregnant women and neonates, as well as studies on the neurological complications of Zika infections in adolescents and adults. For example, the Neuroviruses Emerging in the Americas Study (NEAS) has set up more than 10 clinical sites in Colombia. Through the Butantan Phase 3 dengue vaccine trial, we have access to samples of 17,000 subjects in 14 different geographic locations in Brazil. To address the lack of access to clinical samples for diagnostic evaluation, ZikaPLAN set up a network of quality sites with access to well-characterized clinical specimens and capacity for independent evaluations. The International Committee for Congenital Anomaly Surveillance Tools was formed with global representation from regional networks conducting birth defects surveillance. We have collated a comprehensive inventory of resources and tools for birth defects surveillance, and developed an App for low resource regions facilitating the coding and description of all major externally visible congenital anomalies including congenital Zika syndrome. Research Capacity Network (REDe) is a shared and open resource centre where researchers and health workers can access tools, resources and support, enabling better and more research in the region. Addressing the gap in research capacity in LMICs is pivotal in ensuring broad-based systems to be prepared for the next outbreak. Our shared and open research space through REDe will be used to maximize the transfer of research into practice by summarizing the research output and by hosting the tools, resources, guidance and recommendations generated by these studies. Leveraging on the research from this consortium, we are working towards a research preparedness network.

Automated detection of wrong-drug prescribing errors.

BACKGROUND: To assess the specificity of an algorithm designed to detect look-alike/sound-alike (LASA) medication prescribing errors in electronic health record (EHR) data. SETTING: Urban, academic medical centre, comprising a 495-bed hospital and outpatient clinic running on the Cerner EHR. We extracted 8 years of medication orders and diagnostic claims. We licensed a database of medication indications, refined it and merged it with the medication data. We developed an algorithm that triggered for LASA errors based on name similarity, the frequency with which a patient received a medication and whether the medication was justified by a diagnostic claim. We stratified triggers by similarity. Two clinicians reviewed a sample of charts for the presence of a true error, with disagreements resolved by a third reviewer. We computed specificity, positive predictive value (PPV) and yield. RESULTS: The algorithm analysed 488 481 orders and generated 2404 triggers (0.5% rate). Clinicians reviewed 506 cases and confirmed the presence of 61 errors, for an overall PPV of 12.1% (95% CI 10.7% to 13.5%). It was not possible to measure sensitivity or the false-negative rate. The specificity of the algorithm varied as a function of name similarity and whether the intended and dispensed drugs shared the same route of administration. CONCLUSION: Automated detection of LASA medication errors is feasible and can reveal errors not currently detected by other means. Real-time error detection is not possible with the current system, the main barrier being the real-time availability of accurate diagnostic information. Further development should replicate this analysis in other health systems and on a larger set of medications and should decrease clinician time spent reviewing false-positive triggers by increasing specificity.

ZikaPLAN: addressing the knowledge gaps and working towards a research preparedness network in the Americas

Zika Preparedness Latin American Network (ZikaPLAN) is a research consortium funded by the European Commission to address the research gaps in combating Zika and to establish a sustainable network with research capacity building in the Americas. Here we present a report on ZikaPLAN's mid-term achievements since its initiation in October 2016 to June 2019, illustrating the research objectives of the 15 work packages ranging from virology, diagnostics, entomology and vector control, modelling to clinical cohort studies in pregnant women and neonates, as well as studies on the neurological complications of Zika infections in adolescents and adults. For example, the Neuroviruses Emerging in the Americas Study (NEAS) has set up more than 10 clinical sites in Colombia. Through the Butantan Phase 3 dengue vaccine trial, we have access to samples of 17,000 subjects in 14 different geographic locations in Brazil. To address the lack of access to clinical samples for diagnostic evaluation, ZikaPLAN set up a network of quality sites with access to well-characterized clinical specimens and capacity for independent evaluations. The International Committee for Congenital Anomaly Surveillance Tools was formed with global representation from regional networks conducting birth defects surveillance. We have collated a comprehensive inventory of resources and tools for birth defects surveillance, and developed an App for low resource regions facilitating the coding and description of all major externally visible congenital anomalies including congenital Zika syndrome. Research Capacity Network (REDe) is a shared and open resource centre where researchers and health workers can access tools, resources and support, enabling better and more research in the region. Addressing the gap in research capacity in LMICs is pivotal in ensuring broad-based systems to be prepared for the next outbreak. Our shared and open research space through REDe will be used to maximize the transfer of research into practice by summarizing the research output and by hosting the tools, resources, guidance and recommendations generated by these studies. Leveraging on the research from this consortium, we are working towards a research preparedness network.

ZikaPLAN: addressing the knowledge gaps and working towards a research preparedness network in the Americas

Zika Preparedness Latin American Network (ZikaPLAN) is a research consortium funded by the European Commission to address the research gaps in combating Zika and to establish a sustainable network with research capacity building in the Americas. Here we present a report on ZikaPLAN's mid-term achievements since its initiation in October 2016 to June 2019, illustrating the research objectives of the 15 work packages ranging from virology, diagnostics, entomology and vector control, modelling to clinical cohort studies in pregnant women and neonates, as well as studies on the neurological complications of Zika infections in adolescents and adults. For example, the Neuroviruses Emerging in the Americas Study (NEAS) has set up more than 10 clinical sites in Colombia. Through the Butantan Phase 3 dengue vaccine trial, we have access to samples of 17,000 subjects in 14 different geographic locations in Brazil. To address the lack of access to clinical samples for diagnostic evaluation, ZikaPLAN set up a network of quality sites with access to well-characterized clinical specimens and capacity for independent evaluations. The International Committee for Congenital Anomaly Surveillance Tools was formed with global representation from regional networks conducting birth defects surveillance. We have collated a comprehensive inventory of resources and tools for birth defects surveillance, and developed an App for low resource regions facilitating the coding and description of all major externally visible congenital anomalies including congenital Zika syndrome. Research Capacity Network (REDe) is a shared and open resource centre where researchers and health workers can access tools, resources and support, enabling better and more research in the region. Addressing the gap in research capacity in LMICs is pivotal in ensuring broad-based systems to be prepared for the next outbreak. Our shared and open research space through REDe will be used to maximize the transfer of research into practice by summarizing the research output and by hosting the tools, resources, guidance and recommendations generated by these studies. Leveraging on the research from this consortium, we are working towards a research preparedness network.

Identifying health information technology related safety event reports from patient safety event report databases.

OBJECTIVE: The objective of this paper was to identify health information technology (HIT) related events from patient safety event (PSE) report free-text descriptions. A difference-based scoring approach was used to prioritize and select model features. A feature-constraint model was developed and evaluated to support the analysis of PSE reports. METHODS: 5287 PSE reports manually coded as likely or unlikely related to HIT were used to train unigram, bigram, and combined unigram-bigram logistic regression and support vector machine models using five-fold cross validation. A difference-based scoring approach was used to prioritize and select unigram and bigram features by their relative importance to likely and unlikely HIT reports. A held-out set of 2000 manually coded reports were used for testing. RESULTS: Unigram models tended to perform better than bigram and combined models. A 300-unigram logistic regression had comparable classification performance to a 4030-unigram SVM model but with a faster relative run-time. The 300-unigram logistic regression model evaluated with the testing data had an AUC of 0.931 and a F1-score of 0.765. DISCUSSION: A difference-based scoring, prioritization, and feature selection approach can be used to generate simplified models with high performance. A feature-constraint model may be more easily shared across healthcare organizations seeking to analyze their respective datasets and customized for local variations in PSE reporting practices. CONCLUSION: The feature-constraint model provides a method to identify HIT-related patient safety hazards using a method that is applicable across healthcare systems with variability in their PSE report structures.

Re-visiting the evolution, dispersal and epidemiology of Zika virus in Asia.

Based on serological evidence and viral isolation, Zika virus (ZIKV) has circulated for many years relatively benignly in a sylvatic cycle in Africa and an urban cycle in South East Asia (SEA). With the recent availability of limited but novel Indian ZIKV sequences to add to the plethora of SEA sequences, we traced the phylogenetic history and spatio-temporal dispersal pattern of ZIKV in Asia prior to its explosive emergence in the Pacific region and the Americas. These analyses demonstrated that the introduction and dispersal of ZIKV on the Pacific islands were preceded by an extended period of relatively silent transmission in SEA, enabling the virus to expand geographically and evolve adaptively before its unanticipated introduction to immunologically naive populations on the Pacific islands and in the Americas. Our findings reveal new features of the evolution and dispersal of this intriguing virus and may benefit future disease control strategies.

A Microsatellite-Based Analysis of House Infestation With Triatoma Infestans (Hemiptera: Reduviidae) After Insecticide Spraying in the Argentine Chaco.

Prevention of vector-borne transmission of Chagas disease mainly relies on residual insecticide spraying. Despite significant success at a regional scale, house infestation with Triatoma infestans (Klug) (Hemiptera: Reduviidae) still persists in the Gran Chaco ecoregion. One key aspect is the identification of the sources of reinfestant triatomines. After detecting fine-scale genetic structure in two rural villages of Pampa del Indio, Argentine Chaco, we tested hypotheses on the putative origins of the triatomines collected at 4, 8, and 12 mo after insecticide house spraying. We genotyped 10 microsatellite loci in 262 baseline and 83 postspraying triatomines from different houses. Genetic variability was similar between baseline and postspraying populations, but 13 low-frequency alleles were not detected at postspraying. FSTs were not significant between insects collected before and after insecticide spraying at the same house in all but one case, and they clustered together in a neighbor-joining tree. A clustering algorithm detected seven genetic groups, four of them mainly composed of baseline and postspraying insects from the same house. Assignment tests suggested multiple putative sources (including the house of collection) for most postspraying insects but excluded a house located more than 9 km from the study area. The origin of three triatomines was attributed to immigration from other unaccounted sources. Our study is compatible with the hypothesis that house reinfestations in the Argentine Chaco are mostly related to residual foci (i.e., survival of insects within the same community), in agreement with field observations, spatial analysis, and morphometric studies previously published.

Frequent Undetected Ward-Based Methicillin-Resistant Staphylococcus aureus Transmission Linked to Patient Sharing Between Hospitals.

Background: Recent evidence suggests that hospital transmission of methicillin-resistant Staphylococcus aureus (MRSA) is uncommon in UK centers that have implemented sustained infection control programs. We investigated whether a healthcare-network analysis could shed light on transmission paths currently sustaining MRSA levels in UK hospitals. Methods: A cross-sectional observational study was performed in 2 National Health Service hospital groups and a general district hospital in Southeast London. All MRSA patients identified at inpatient, outpatient, and community settings between 1 November 2011 and 29 February 2012 were included. We identified genetically defined MRSA transmission clusters in individual hospitals and across the healthcare network, and examined genetic differentiation of sequence type (ST) 22 MRSA isolates within and between hospitals and inpatient or outpatient and community settings, as informed by average and median pairwise single-nucleotide polymorphisms (SNPs) and SNP-based proportions of nearly identical isolates. Results: Two hundred forty-eight of 610 (40.7%) MRSA patients were linked in 90 transmission clusters, of which 27 spanned multiple hospitals. Analysis of a large 32 patient ST22-MRSA cluster showed that 26 of 32 patients (81.3%) had multiple contacts with one another during ward stays at any hospital. No residential, outpatient, or significant community healthcare contacts were identified. Genetic differentiation between ST22 MRSA inpatient isolates from different hospitals was less than between inpatient isolates from the same hospitals (P ≤ .01). Conclusions: There is evidence of frequent ward-based transmission of MRSA brought about by frequent patient admissions to multiple hospitals. Limiting in-ward transmission requires sharing of MRSA status data between hospitals.

An Analysis of Patient Safety Incident Reports Associated with Electronic Health Record Interoperability

Background: With the widespread use of electronic health records (EHRs) for many clinical tasks, interoperability with other health information technology (health IT) is critical for the effective delivery of care. While it is generally recognized that poor interoperability negatively impacts patient care, little is known about the specific patient safety implications. Understanding the patient safety implications will help prioritize interoperability efforts around architectures and standards. Objectives: Our objectives were to (1) identify patient safety incident reports that reflect EHR interoperability challenges with other health IT, and (2) perform a detailed analysis of these reports to understand the health IT systems involved, the clinical care processes impacted, whether the incident occurred within or between provider organizations, and the reported severity of the patient safety events. Methods: From a database of 1.735 million patient safety event (PSE) reports spanning multiple provider organizations, 2625 reports that were indicated as being health IT related by the event reporter were reviewed to identify EHR interoperability related reports. Through a rigorous coding process 209 EHR interoperability related events were identified and coded. Results: The majority of EHR interoperability PSE reports involved interfacing with pharmacy systems (i.e. medication related), followed by laboratory, and radiology. Most of the interoperability challenges in these clinical areas were associated with the EHR receiving information from other health IT systems as opposed to the EHR sending information to other systems. The majority of EHR interoperability challenges were within a provider organization and while many of the safety events reached the patient, only a few resulted in patient harm. Conclusions: Interoperability efforts should prioritize systems in pharmacy, laboratory, and radiology. Providers should recognize the need to improve EHRs interfacing with other health IT systems within their own organization.

Cognitive tests predict real-world errors: the relationship between drug name confusion rates in laboratory-based memory and perception tests and corresponding error rates in large pharmacy chains.

BACKGROUND: Drug name confusion is a common type of medication error and a persistent threat to patient safety. In the USA, roughly one per thousand prescriptions results in the wrong drug being filled, and most of these errors involve drug names that look or sound alike. Prior to approval, drug names undergo a variety of tests to assess their potential for confusability, but none of these preapproval tests has been shown to predict real-world error rates. OBJECTIVES: We conducted a study to assess the association between error rates in laboratory-based tests of drug name memory and perception and real-world drug name confusion error rates. METHODS: Eighty participants, comprising doctors, nurses, pharmacists, technicians and lay people, completed a battery of laboratory tests assessing visual perception, auditory perception and short-term memory of look-alike and sound-alike drug name pairs (eg, hydroxyzine/hydralazine). RESULTS: Laboratory test error rates (and other metrics) significantly predicted real-world error rates obtained from a large, outpatient pharmacy chain, with the best-fitting model accounting for 37% of the variance in real-world error rates. Cross-validation analyses confirmed these results, showing that the laboratory tests also predicted errors from a second pharmacy chain, with 45% of the variance being explained by the laboratory test data. CONCLUSIONS: Across two distinct pharmacy chains, there is a strong and significant association between drug name confusion error rates observed in the real world and those observed in laboratory-based tests of memory and perception. Regulators and drug companies seeking a validated preapproval method for identifying confusing drug names ought to consider using these simple tests. By using a standard battery of memory and perception tests, it should be possible to reduce the number of confusing look-alike and sound-alike drug name pairs that reach the market, which will help protect patients from potentially harmful medication errors.

How Did Zika Virus Emerge in the Pacific Islands and Latin America?

The unexpected emergence of Zika virus (ZIKV) in the Pacific Islands and Latin America and its association with congenital Zika virus syndrome (CZVS) (which includes microcephaly) and Guillain-Barré syndrome (GBS) have stimulated wide-ranging research. High densities of susceptible Aedes spp., immunologically naive human populations, global population growth with increased urbanization, and escalation of global transportation of humans and commercial goods carrying vectors and ZIKV undoubtedly enhanced the emergence of ZIKV. However, flavivirus mutations accumulate with time, increasing the likelihood that genetic viral differences are determinants of change in viral phenotype. Based on comparative ZIKV complete genome phylogenetic analyses and temporal estimates, we identify amino acid substitutions that may be associated with increased viral epidemicity, CZVS, and GBS. Reverse genetics, vector competence, and seroepidemiological studies will test our hypothesis that these amino acid substitutions are determinants of epidemic and neurotropic ZIKV emergence.

Characterizing the pain score trajectories of hospitalized adult medical and surgical patients: a retrospective cohort study.

Pain care for hospitalized patients is often suboptimal. Representing pain scores as a graphical trajectory may provide insights into the understanding and treatment of pain. We describe a 1-year, retrospective, observational study to characterize pain trajectories of hospitalized adults during the first 48 hours after admission at an urban academic medical center. Using a subgroup of patients who presented with significant pain (pain score >4; n = 7762 encounters), we characterized pain trajectories and measured area under the curve, slope of the trajectory for the first 2 hours after admission, and pain intensity at plateau. We used mixed-effects regression to assess the association between pain score and sociodemographics (age, race, and gender), pain medication orders (opioids, nonopioids, and no medications), and medical service (obstetrics, psychiatry, surgery, sickle cell, intensive care unit, and medicine). K-means clustering was used to identify patient subgroups with similar trajectories. Trajectories showed differences based on race, gender, service, and initial pain score. Patients presumed to have dissimilar pain experiences (eg, sickle vs obstetrical) had markedly different pain trajectories. Patients with higher initial pain had a more rapid reduction during their first 2 hours of treatment. Pain reduction achieved in the 48 hours after admission was approximately 50% of the initial pain, regardless of the initial pain. Most patients' pain failed to fully resolve, plateauing at a pain score of 4 or greater. Visualizing pain scores as graphical trajectories illustrates the dynamic variability in pain, highlighting pain responses over a period of observation, and may yield new insights for quality improvement and research.

Avoiding Medication Errors: Reducing Harm in Residents Using Oral Anticoagulants.

Medication errors involving oral anticoagulants have led to serious adverse events, including hemorrhage, treatment failures leading to thromboembolic events, and death. This article will highlight medication errors that may arise during the use of oral anticoagulants and provide risk-reduction strategies to address the potential for error and patient harm.

Evidence for Community Transmission of Community-Associated but Not Health-Care-Associated Methicillin-Resistant Staphylococcus Aureus Strains Linked to Social and Material Deprivation: Spatial Analysis of Cross-sectional Data.

BACKGROUND: Identifying and tackling the social determinants of infectious diseases has become a public health priority following the recognition that individuals with lower socioeconomic status are disproportionately affected by infectious diseases. In many parts of the world, epidemiologically and genotypically defined community-associated (CA) methicillin-resistant Staphylococcus aureus (MRSA) strains have emerged to become frequent causes of hospital infection. The aim of this study was to use spatial models with adjustment for area-level hospital attendance to determine the transmission niche of genotypically defined CA- and health-care-associated (HA)-MRSA strains across a diverse region of South East London and to explore a potential link between MRSA carriage and markers of social and material deprivation. METHODS AND FINDINGS: This study involved spatial analysis of cross-sectional data linked with all MRSA isolates identified by three National Health Service (NHS) microbiology laboratories between 1 November 2011 and 29 February 2012. The cohort of hospital-based NHS microbiology diagnostic services serves 867,254 usual residents in the Lambeth, Southwark, and Lewisham boroughs in South East London, United Kingdom (UK). Isolates were classified as HA- or CA-MRSA based on whole genome sequencing. All MRSA cases identified over 4 mo within the three-borough catchment area (n = 471) were mapped to small geographies and linked to area-level aggregated socioeconomic and demographic data. Disease mapping and ecological regression models were used to infer the most likely transmission niches for each MRSA genetic classification and to describe the spatial epidemiology of MRSA in relation to social determinants. Specifically, we aimed to identify demographic and socioeconomic population traits that explain cross-area extra variation in HA- and CA-MRSA relative risks following adjustment for hospital attendance data. We explored the potential for associations with the English Indices of Deprivation 2010 (including the Index of Multiple Deprivation and several deprivation domains and subdomains) and the 2011 England and Wales census demographic and socioeconomic indicators (including numbers of households by deprivation dimension) and indicators of population health. Both CA-and HA-MRSA were associated with household deprivation (CA-MRSA relative risk [RR]: 1.72 [1.03-2.94]; HA-MRSA RR: 1.57 [1.06-2.33]), which was correlated with hospital attendance (Pearson correlation coefficient [PCC] = 0.76). HA-MRSA was also associated with poor health (RR: 1.10 [1.01-1.19]) and residence in communal care homes (RR: 1.24 [1.12-1.37]), whereas CA-MRSA was linked with household overcrowding (RR: 1.58 [1.04-2.41]) and wider barriers, which represent a combined score for household overcrowding, low income, and homelessness (RR: 1.76 [1.16-2.70]). CA-MRSA was also associated with recent immigration to the UK (RR: 1.77 [1.19-2.66]). For the area-level variation in RR for CA-MRSA, 28.67% was attributable to the spatial arrangement of target geographies, compared with only 0.09% for HA-MRSA. An advantage to our study is that it provided a representative sample of usual residents receiving care in the catchment areas. A limitation is that relationships apparent in aggregated data analyses cannot be assumed to operate at the individual level. CONCLUSIONS: There was no evidence of community transmission of HA-MRSA strains, implying that HA-MRSA cases identified in the community originate from the hospital reservoir and are maintained by frequent attendance at health care facilities. In contrast, there was a high risk of CA-MRSA in deprived areas linked with overcrowding, homelessness, low income, and recent immigration to the UK, which was not explainable by health care exposure. Furthermore, areas adjacent to these deprived areas were themselves at greater risk of CA-MRSA, indicating community transmission of CA-MRSA. This ongoing community transmission could lead to CA-MRSA becoming the dominant strain types carried by patients admitted to hospital, particularly if successful hospital-based MRSA infection control programmes are maintained. These results suggest that community infection control programmes targeting transmission of CA-MRSA will be required to control MRSA in both the community and hospital. These epidemiological changes will also have implications for effectiveness of risk-factor-based hospital admission MRSA screening programmes.