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Knockout of the ORF8 protein has repeatedly spread through the global viral population during SARS-CoV-2 evolution. Here we use both regional and global pathogen sequencing to explore the selection pressures underlying its loss. In Washington State, we identified transmission clusters with ORF8 knockout throughout SARS-CoV-2 evolution, not just on novel, high fitness viral backbones. Indeed, ORF8 is truncated more frequently and knockouts circulate for longer than for any other gene. Using a global phylogeny, we find evidence of positive selection to explain this phenomenon: nonsense mutations resulting in shortened protein products occur more frequently and are associated with faster clade growth rates than synonymous mutations in ORF8. Loss of ORF8 is also associated with reduced clinical severity, highlighting the diverse clinical impacts of SARS-CoV-2 evolution.
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COVID-19 , SARS-CoV-2 , Selección Genética , Humanos , Filogenia , SARS-CoV-2/genética , Proteínas Virales/genética , Selección Genética/genéticaRESUMEN
SARS-CoV-2 transmission is largely driven by heterogeneous dynamics at a local scale, leaving local health departments to design interventions with limited information. We analyzed SARS-CoV-2 genomes sampled between February 2020 and March 2022 jointly with epidemiological and cell phone mobility data to investigate fine scale spatiotemporal SARS-CoV-2 transmission dynamics in King County, Washington, a diverse, metropolitan US county. We applied an approximate structured coalescent approach to model transmission within and between North King County and South King County alongside the rate of outside introductions into the county. Our phylodynamic analyses reveal that following stay-at-home orders, the epidemic trajectories of North and South King County began to diverge. We find that South King County consistently had more reported and estimated cases, COVID-19 hospitalizations, and longer persistence of local viral transmission when compared to North King County, where viral importations from outside drove a larger proportion of new cases. Using mobility and demographic data, we also find that South King County experienced a more modest and less sustained reduction in mobility following stay-at-home orders than North King County, while also bearing more socioeconomic inequities that might contribute to a disproportionate burden of SARS-CoV-2 transmission. Overall, our findings suggest a role for local-scale phylodynamics in understanding the heterogeneous transmission landscape.
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COVID-19 , Epidemias , Humanos , SARS-CoV-2/genética , COVID-19/epidemiología , Washingtón/epidemiologíaRESUMEN
Coccidioidomycosis, histoplasmosis, and blastomycosis are lower respiratory tract fungal infections whose signs and symptoms can resemble those of other respiratory illnesses, including pneumonia caused by bacterial or viral etiologies; this overlap in clinical presentation might lead to missed or delayed diagnoses. The causative fungi live in the environment, often in soil or plant matter. To describe the epidemiologic characteristics of cases of coccidioidomycosis, histoplasmosis, and blastomycosis during the COVID-19 pandemic, CDC analyzed case surveillance data for 2019-2021. During this period, a total of 59,655 coccidioidomycosis cases, 3,595 histoplasmosis cases, and 719 blastomycosis cases were reported to CDC. In 2020, fewer cases of each disease occurred in spring compared with other seasons, and most cases occurred in fall; national seasonality is not typically observed, and cases were seasonally distributed more evenly in 2019 and 2021. Fewer cases coinciding with the start of the COVID-19 pandemic, along with an unusually high blastomycosis case fatality rate in 2021 (17% compared with more typical rates of 8%-10%), suggest that the pandemic might have affected patients' health care-seeking behavior, public health reporting practices, or clinical management of these diseases. Increased awareness and education are needed to encourage health care providers to consider fungal diseases and to identify pneumonia of fungal etiology. Standardized diagnostic guidance and informational resources for fungal testing could be incorporated into broader respiratory disease awareness and preparedness efforts to improve early diagnosis of coccidioidomycosis, histoplasmosis, and blastomycosis.
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Blastomicosis , COVID-19 , Coccidioidomicosis , Histoplasmosis , Infecciones del Sistema Respiratorio , Humanos , Estados Unidos/epidemiología , Blastomicosis/epidemiología , Histoplasmosis/diagnóstico , Histoplasmosis/epidemiología , Histoplasmosis/microbiología , Coccidioidomicosis/diagnóstico , Coccidioidomicosis/epidemiología , Pandemias , COVID-19/epidemiología , Infecciones del Sistema Respiratorio/epidemiologíaRESUMEN
Tularemia is caused by the highly infectious bacterium Francisella tularensis, which is recognized as a Tier 1 bioterrorism agent. Tularemia has a range of recognized clinical manifestations, but fewer than 20 bone or joint infections from 6 countries have been reported in the literature to date. This series includes 13 cases of F. tularensis septic arthritis or osteomyelitis in the United States during 2004-2023 and describes exposures, clinical presentation, diagnosis, and outcomes for this rare but severe form of tularemia. Clinicians should consider F. tularensis in patients with compatible exposures or a history of joint replacement or immunosuppression.
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Artritis Infecciosa , Francisella tularensis , Tularemia , Humanos , Estados Unidos/epidemiología , Tularemia/diagnóstico , Tularemia/epidemiología , Tularemia/microbiología , Artritis Infecciosa/diagnóstico , Artritis Infecciosa/epidemiologíaRESUMEN
BACKGROUND: Long-term care facilities (LTCFs) are vulnerable to disease outbreaks. Here, we jointly analyze SARS-CoV-2 genomic and paired epidemiologic data from LTCFs and surrounding communities in Washington state (WA) to assess transmission patterns during 2020-2022, in a setting of changing policy. We describe sequencing efforts and genomic epidemiologic findings across LTCFs and perform in-depth analysis in a single county. METHODS: We assessed genomic data representativeness, built phylogenetic trees, and conducted discrete trait analysis to estimate introduction sizes over time, and explored selected outbreaks to further characterize transmission events. RESULTS: We found that transmission dynamics among cases associated with LTCFs in WA changed over the course of the COVID-19 pandemic, with variable introduction rates into LTCFs, but decreasing amplification within LTCFs. SARS-CoV-2 lineages circulating in LTCFs were similar to those circulating in communities at the same time. Transmission between staff and residents was bi-directional. CONCLUSIONS: Understanding transmission dynamics within and between LTCFs using genomic epidemiology on a broad scale can assist in targeting policies and prevention efforts. Tracking facility-level outbreaks can help differentiate intra-facility outbreaks from high community transmission with repeated introduction events. Based on our study findings, methods for routine tree building and overlay of epidemiologic data for hypothesis generation by public health practitioners are recommended. Discrete trait analysis added valuable insight and can be considered when representative sequencing is performed. Cluster detection tools, especially those that rely on distance thresholds, may be of more limited use given current data capture and timeliness. Importantly, we noted a decrease in data capture from LTCFs over time. Depending on goals for use of genomic data, sentinel surveillance should be increased or targeted surveillance implemented to ensure available data for analysis.
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COVID-19 , Humanos , COVID-19/epidemiología , Pandemias/prevención & control , SARS-CoV-2/genética , Washingtón/epidemiología , Cuidados a Largo Plazo/métodos , Filogenia , GenómicaRESUMEN
Chlamydia psittaci is a bacterium that causes chlamydiosis in birds and can cause zoonotic psittacosis in people. In November 2017, we received notification of a suspected case of avian chlamydiosis in a captive cockatiel (Nymphicus hollandicus) that was sold by an online pet bird retail and breeding facility in Washington State. We describe the investigation with emphasis on how environmental sampling was used to guide veterinary and public health interventions. Bird samples were collected either from pooled droppings, pooled plumage or individual nasal and choanal swabs. Environmental samples were obtained by swabbing cleaning mops, tables and cage structures. All samples were tested by polymerase chain reaction and positive samples underwent genotyping. Approximately 1000 birds representing four taxonomic orders were kept within an open-space warehouse. Eight of 14 environmental samples and one of two pooled faecal samples were positive for Chlamydia spp. The contaminating strain of Chlamydia spp. was identified as genotype A. The facility was closed for environmental disinfection, and all psittacines were treated with oral doxycycline for 45 days. Ten of 10 environmental and two of two pooled faecal samples were negative for C. psittaci 11 months after the completion of environmental disinfection and antimicrobial treatment. This investigation highlights the importance of preventing and mitigating pathogen incursion in an online pet retail and breeding facility. Environmental sampling is valuable to guide animal and public health interventions for control of C. psittaci, particularly when large numbers of birds are exposed to the pathogen.
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Enfermedades de las Aves , Chlamydophila psittaci , Psitacosis , Animales , Psitacosis/veterinaria , Psitacosis/microbiología , Enfermedades de las Aves/microbiología , Aves , Chlamydophila psittaci/genética , DoxiciclinaRESUMEN
We describe a case of Baylisascaris procyonis roundworm infection in a child in Washington, USA, with autism spectrum disorder. Environmental assessment confirmed nearby raccoon habitation and B. procyonis eggs. B. procyonis infections should be considered a potential cause of human eosinophilic meningitis, particularly among young children and persons with developmental delays.
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Infecciones por Ascaridida , Ascaridoidea , Trastorno del Espectro Autista , Animales , Humanos , Niño , Preescolar , Washingtón/epidemiología , Infecciones por Ascaridida/diagnóstico , MapachesRESUMEN
Genomic data provides useful information for public health practice, particularly when combined with epidemiologic data. However, sampling bias is a concern because inferences from nonrandom data can be misleading. In March 2021, the Washington State Department of Health, USA, partnered with submitting and sequencing laboratories to establish sentinel surveillance for SARS-CoV-2 genomic data. We analyzed available genomic and epidemiologic data during presentinel and sentinel periods to assess representativeness and timeliness of availability. Genomic data during the presentinel period was largely unrepresentative of all COVID-19 cases. Data available during the sentinel period improved representativeness for age, death from COVID-19, outbreak association, long-term care facility-affiliated status, and geographic coverage; timeliness of data availability and captured viral diversity also improved. Hospitalized cases were underrepresented, indicating a need to increase inpatient sampling. Our analysis emphasizes the need to understand and quantify sampling bias in phylogenetic studies and continue evaluation and improvement of public health surveillance systems.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/epidemiología , Washingtón/epidemiología , Vigilancia de Guardia , Filogenia , GenómicaRESUMEN
SARS-CoV-2 transmission is largely driven by heterogeneous dynamics at a local scale, leaving local health departments to design interventions with limited information. We analyzed SARS-CoV-2 genomes sampled between February 2020 and March 2022 jointly with epidemiological and cell phone mobility data to investigate fine scale spatiotemporal SARS-CoV-2 transmission dynamics in King County, Washington, a diverse, metropolitan US county. We applied an approximate structured coalescent approach to model transmission within and between North King County and South King County alongside the rate of outside introductions into the county. Our phylodynamic analyses reveal that following stay-at-home orders, the epidemic trajectories of North and South King County began to diverge. We find that South King County consistently had more reported and estimated cases, COVID-19 hospitalizations, and longer persistence of local viral transmission when compared to North King County, where viral importations from outside drove a larger proportion of new cases. Using mobility and demographic data, we also find that South King County experienced a more modest and less sustained reduction in mobility following stay-at-home orders than North King County, while also bearing more socioeconomic inequities that might contribute to a disproportionate burden of SARS-CoV-2 transmission. Overall, our findings suggest a role for local-scale phylodynamics in understanding the heterogeneous transmission landscape.
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BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is dominated by variant viruses; the resulting impact on disease severity remains unclear. Using a retrospective cohort study, we assessed the hospitalization risk following infection with 7 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. METHODS: Our study includes individuals with positive SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) in the Washington Disease Reporting System with available viral genome data, from 1 December 2020 to 14 January 2022. The analysis was restricted to cases with specimens collected through sentinel surveillance. Using a Cox proportional hazards model with mixed effects, we estimated hazard ratios (HR) for hospitalization risk following infection with a variant, adjusting for age, sex, calendar week, and vaccination. RESULTS: In total, 58 848 cases were sequenced through sentinel surveillance, of which 1705 (2.9%) were hospitalized due to COVID-19. Higher hospitalization risk was found for infections with Gamma (HR 3.20, 95% confidence interval [CI] 2.40-4.26), Beta (HR 2.85, 95% CI 1.56-5.23), Delta (HR 2.28 95% CI 1.56-3.34), or Alpha (HR 1.64, 95% CI 1.29-2.07) compared to infections with ancestral lineages; Omicron (HR 0.92, 95% CI .56-1.52) showed no significant difference in risk. Following Alpha, Gamma, or Delta infection, unvaccinated patients show higher hospitalization risk, while vaccinated patients show no significant difference in risk, both compared to unvaccinated, ancestral lineage cases. Hospitalization risk following Omicron infection is lower with vaccination. CONCLUSIONS: Infection with Alpha, Gamma, or Delta results in a higher hospitalization risk, with vaccination attenuating that risk. Our findings support hospital preparedness, vaccination, and genomic surveillance.
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COVID-19 , SARS-CoV-2 , COVID-19/epidemiología , Hospitalización , Humanos , Estudios Retrospectivos , SARS-CoV-2/genética , Washingtón/epidemiologíaRESUMEN
BACKGROUND: The COVID-19 pandemic is dominated by variant viruses; the resulting impact on disease severity remains unclear. Using a retrospective cohort study, we assessed the hospitalization risk following infection with seven SARS-CoV-2 variants. METHODS: Our study includes individuals with positive SARS-CoV-2 RT-PCR in the Washington Disease Reporting System with available viral genome data, from December 1, 2020 to January 14, 2022. The analysis was restricted to cases with specimens collected through sentinel surveillance. Using a Cox proportional hazards model with mixed effects, we estimated hazard ratios (HR) for hospitalization risk following infection with a variant, adjusting for age, sex, calendar week, and vaccination. FINDINGS: 58,848 cases were sequenced through sentinel surveillance, of which 1705 (2.9%) were hospitalized due to COVID-19. Higher hospitalization risk was found for infections with Gamma (HR 3.20, 95%CI 2.40-4.26), Beta (HR 2.85, 95%CI 1.56-5.23), Delta (HR 2.28 95%CI 1.56-3.34) or Alpha (HR 1.64, 95%CI 1.29-2.07) compared to infections with ancestral lineages; Omicron (HR 0.92, 95%CI 0.56-1.52) showed no significant difference in risk. Following Alpha, Gamma, or Delta infection, unvaccinated patients show higher hospitalization risk, while vaccinated patients show no significant difference in risk, both compared to unvaccinated, ancestral lineage cases. Hospitalization risk following Omicron infection is lower with vaccination. CONCLUSION: Infection with Alpha, Gamma, or Delta results in a higher hospitalization risk, with vaccination attenuating that risk. Our findings support hospital preparedness, vaccination, and genomic surveillance. SUMMARY: Hospitalization risk following infection with SARS-CoV-2 variant remains unclear. We find a higher hospitalization risk in cases infected with Alpha, Beta, Gamma, and Delta, but not Omicron, with vaccination lowering risk. Our findings support hospital preparedness, vaccination, and genomic surveillance.
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Coccidioides immitis and Coccidioides posadasii are causative agents of Valley fever, a serious fungal disease endemic to regions with hot, arid climate in the United States, Mexico, and Central and South America. The environmental niche of Coccidioides spp. is not well defined, and it remains unknown whether these fungi are primarily associated with rodents or grow as saprotrophs in soil. To better understand the environmental reservoir of these pathogens, we used a systematic soil sampling approach, quantitative PCR (qPCR), culture, whole-genome sequencing, and soil chemical analysis to identify factors associated with the presence of C. immitis at a known colonization site in Washington State linked to a human case in 2010. We found that the same strain colonized an area of over 46,000 m2 and persisted in soil for over 6 years. No association with rodent burrows was observed, as C. immitis DNA was as likely to be detected inside rodent holes as it was in the surrounding soil. In addition, the presence of C. immitis DNA in soil was correlated with elevated levels of boron, calcium, magnesium, sodium, and silicon in soil leachates. We also observed differences in the microbial communities between C. immitis-positive and -negative soils. Our artificial soil inoculation experiments demonstrated that C. immitis can use soil as a sole source of nutrients. Taken together, these results suggest that soil parameters need to be considered when modeling the distribution of this fungus in the environment. IMPORTANCE Coccidioidomycosis is considered a highly endemic disease for which geographic range is likely to expand from climate change. A better understanding of the ecological niche of Coccidioides spp. is essential for generating accurate distribution maps and predicting future changes in response to the changing environment. Our study used a systematic sampling strategy, advanced molecular detection methods, and soil chemical analysis to identify environmental factors associated with the presence of C. immitis in soil. Our results demonstrate the fungus can colonize the same areas for years and is associated with chemical and microbiological soil characteristics. Our results suggest that in addition to climate parameters, soil characteristics need to be considered when building habitat distribution models for this pathogen.
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Coccidioides/aislamiento & purificación , Coccidioidomicosis/epidemiología , Coccidioidomicosis/microbiología , Microbiología del Suelo , Coccidioides/genética , ADN de Hongos/química , ADN de Hongos/genética , Enfermedades Endémicas , Humanos , Reacción en Cadena en Tiempo Real de la Polimerasa , WashingtónRESUMEN
Tickborne diseases are rare in Washington, USA, and the ecology of these pathogens is poorly understood. We integrated surveillance data from humans and ticks to better describe their epidemiology and ecology. During 2011-2016, a total of 202 tickborne disease cases were reported in Washington residents. Of these, 68 (34%) were autochthonous, including cases of Lyme disease, Rocky Mountain spotted fever, tickborne relapsing fever, and tularemia. During May 2011-December 2016, we collected 977 host-seeking ticks, including Ixodes pacificus, I. angustus, I. spinipalpis, I. auritulus, Dermacentor andersoni, and D. variabilis ticks. The prevalence of Borrelia burgdorferi sensu stricto in I. pacificus ticks was 4.0%; of B. burgdorferi sensu lato, 3.8%; of B. miyamotoi, 4.4%; and of Anaplasma phagocytophilum, 1.9%. We did not detect Rickettsia rickettsii in either Dermacentor species. Case-patient histories and detection of pathogens in field-collected ticks indicate that several tickborne pathogens are endemic to Washington.
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Anaplasma phagocytophilum , Borrelia burgdorferi , Ixodes , Enfermedad de Lyme , Anaplasma phagocytophilum/genética , Animales , Humanos , Washingtón/epidemiologíaRESUMEN
The full geographic range of coccidioidomycosis is unknown, although it is most likely expanding with environmental change. We report an apparently autochthonous coccidioidomycosis patient from Spokane, Washington, USA, a location to which Coccidioides spp. are not known to be endemic.
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Coccidioides/aislamiento & purificación , Coccidioidomicosis/diagnóstico , Neumonía/diagnóstico , Anciano de 80 o más Años , Antifúngicos/uso terapéutico , Coccidioidomicosis/diagnóstico por imagen , Coccidioidomicosis/tratamiento farmacológico , Tos/etiología , Diagnóstico Diferencial , Femenino , Fluconazol/uso terapéutico , Humanos , Neumonía/diagnóstico por imagen , Neumonía/tratamiento farmacológico , WashingtónRESUMEN
Coccidioides immitis is an emerging fungal pathogen in Washington State (WA). While the geographical boundaries of C. immitis in WA have not been well characterized, human infections have resulted from exposure in the south-central region of the state. Since 2010, only one dog has been identified as a probable locally acquired animal case, despite pilot canine serological surveys from south-central WA revealing a 9.8% seroprevalence. On the suspicion that clinical animal cases may be underdiagnosed and/or underreported, we assessed WA veterinarians' knowledge, attitudes and practices regarding coccidioidomycosis. All veterinarians with active licenses in WA were invited to complete a self-administered, web-based survey from November 2018 to January 2019. Four hundred and twenty-five of 2,211 (19.2%) veterinarians returned the survey and were eligible for inclusion in the final analysis. Nearly, all respondents (98.8%) had heard of coccidioidomycosis, but only 31.5% and 25.6% knew that locally acquired animal and human cases, respectively, had been reported in WA. Only half (52.6%) of participants knew that the disease was reportable. Fewer than 20% of respondents reported confidence that their knowledge of coccidioidomycosis was up to date, and 76.9% "never" or "rarely" considered the risk of disease in their patients. A statistically significant predictor of a high knowledge score (≥70%), however, included practicing in endemic counties where the Washington State Department of Health had previously delivered outreach and education services. While the results suggest some success with these activities, it is clear that information on the emergence of coccidioidomycosis is not adequately reaching veterinary practitioners in WA. The data support that more frequent CE opportunities, and dissemination of public health communications through veterinary-specific modalities, would help fill the knowledge gap. In turn, improved diagnosis and reporting of animal cases would assist in our overall understanding the epidemiology of coccidioidomycosis in WA.
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Coccidioides , Coccidioidomicosis/veterinaria , Enfermedades Transmisibles Emergentes/veterinaria , Conocimientos, Actitudes y Práctica en Salud , Veterinarios , Animales , Coccidioidomicosis/epidemiología , Enfermedades Transmisibles Emergentes/epidemiología , Enfermedades Transmisibles Emergentes/microbiología , Recolección de Datos , Enfermedades de los Perros/epidemiología , Perros , Humanos , Encuestas y Cuestionarios , Washingtón/epidemiologíaRESUMEN
Escherichia coli O157:H7 is the predominant cause of diarrhea-associated hemolytic uremic syndrome (HUS) worldwide. Its cardinal virulence traits are Shiga toxins, which are encoded by stx genes, the most common of which are stx1a, stx2a, and stx2c. The toxins these genes encode differ in their in vitro and experimental phenotypes, but the human population-level impact of these differences is poorly understood. Using Shiga toxin-encoding bacteriophage insertion typing and real-time polymerase chain reaction, we genotyped isolates from 936 E. coli O157:H7 cases and verified HUS status via chart review. We compared the HUS risk between isolates with stx2a and those with stx2a and another gene and estimated additive interaction of the stx genes. Adjusted for age and symptoms, the HUS incidence of E. coli O157:H7 containing stx2a alone was 4.4% greater (95% confidence interval (CI) -0.3%, 9.1%) than when it occurred with stx1a. When stx1a and stx2a occur together, the risk of HUS was 27.1% lower (95% CI -87.8%, -2.3%) than would be expected if interaction were not present. At the population level, temporal or geographic shifts toward these genotypes should be monitored, and stx genotype may be an important consideration in clinically predicting HUS among E. coli O157:H7 cases.
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Infecciones por Escherichia coli/microbiología , Escherichia coli O157/genética , Síndrome Hemolítico-Urémico/microbiología , Toxina Shiga/genética , Virulencia/genética , Adolescente , Adulto , Niño , Preescolar , Infecciones por Escherichia coli/terapia , Escherichia coli O157/aislamiento & purificación , Escherichia coli O157/patogenicidad , Genotipo , Síndrome Hemolítico-Urémico/terapia , Humanos , Persona de Mediana Edad , Terapia de Reemplazo Renal , Riesgo , Adulto JovenRESUMEN
Coccidioidomycosis is an emerging fungal infection in Washington, USA, and the epidemiology of the disease in this state is poorly understood. We used whole-genome sequencing to differentiate locally acquired cases in Washington on the basis of the previously identified phylogeographic population structure of Coccidioides spp. Clinical isolates from coccidioidomycosis cases involving possible Washington soil exposure were included. Of 17 human infections with epidemiologic evidence of possible local acquisition, 4 were likely locally acquired infections and 13 were likely acquired outside Washington. Isolates from locally acquired cases clustered within the previously established Washington clade of C. immitis. Genetic differences among these strains suggest multiple environmental reservoirs of C. immitis in the state.
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Coccidioides/genética , Coccidioidomicosis/epidemiología , Coccidioidomicosis/microbiología , Genoma Bacteriano , Secuenciación Completa del Genoma , Coccidioides/clasificación , Coccidioides/aislamiento & purificación , Biología Computacional/métodos , Genómica/métodos , Humanos , Filogenia , Polimorfismo de Nucleótido Simple , Vigilancia en Salud Pública , Washingtón/epidemiologíaRESUMEN
BACKGROUND: Multiple case definitions for post-diarrheal hemolytic uremic syndrome (D+ HUS) associated with Shiga toxin-producing Escherichia coli (STEC) are used across public health, research, and clinical practice. METHODS: To identify a single definition of D+ HUS for standardized use, we evaluated the comparability and validity of four common, heterogeneous definitions: the Council of State and Territorial Epidemiologists (CSTE) definition, hematology-focused and age-focused definitions from the literature, and hospital diagnosis. We reviewed medical records from 471 hospitalized E. coli O157:H7 cases reported in Washington State, 2005-2014. We assessed 1) reliability across definitions, 2) comparability of temporal trends, and 3) sensitivity and specificity using an omnibus reference standard, developed using a combination of definition agreement and clinical outcomes. With the standard, we classified cases as definite, borderline, or unlikely/not post-diarrheal D+ HUS. RESULTS: Reliability was highest between the age-focused definition and hospital diagnosis (κ = 0.84), and temporal trends were largely comparable across definitions. For definite D+ HUS cases, the age-focused definition had the highest overall validity [100% sensitivity, 95% confidence interval (CI): 94%, 100%; 96% specificity, 95% CI: 94%, 98%]. The CSTE definition had low specificity (75%, 95% CI: 70%, 79%). CONCLUSIONS: In this review, the CSTE definition overestimated the burden of D+ HUS, and the age-focused definition provided the best overall reliability and validity to define post-diarrheal D+ HUS. Disease monitoring and research activities should consider using the age-focused D+ HUS definition.
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Diarrea/complicaciones , Infecciones por Escherichia coli/complicaciones , Escherichia coli O157/aislamiento & purificación , Síndrome Hemolítico-Urémico/diagnóstico , Síndrome Hemolítico-Urémico/etiología , Diagnóstico Diferencial , Diarrea/epidemiología , Femenino , Síndrome Hemolítico-Urémico/epidemiología , Humanos , Incidencia , Masculino , Guías de Práctica Clínica como Asunto , Estudios Retrospectivos , Sensibilidad y Especificidad , Escherichia coli Shiga-Toxigénica/aislamiento & purificación , Washingtón/epidemiologíaRESUMEN
BACKGROUND: The veracity of the association between antibiotic use and hemolytic uremic syndrome (HUS) caused by Escherichia coli O157:H7 has been a topic of debate. We postulated that criteria used to define HUS affect this association. METHODS: We reviewed 471 hospitalized E. coli O157:H7 cases reported in Washington State, 2005-2014, to determine HUS status by various case definitions and antibiotic treatment. We used age-adjusted logistic regression models to estimate the effect of treatment on HUS status according to four common, but heterogeneous, definitions: the Council of State and Territorial Epidemiologists (CSTE) definition, hematology-focused and age-focused definitions from the literature, and hospital diagnosis. RESULTS: Inter-annual variation in antibiotic use was high, but no meaningful change in antibiotic use was observed over this ten-year period. Thirteen percent of cases <18 years-old received antibiotics, compared to 54% of cases ≥18 years-old. The CSTE, hematology-focused, age-focused, and hospital diagnosis definitions identified 149, 57, 74, and 89 cases of HUS, respectively. The association between antibiotic treatment and HUS varied by definition: CSTE odds ratio (OR) 1.57 [95% confidence interval (CI) 0.98, 2.55]; hematology-focused OR 1.73 (95% CI 0.83, 3.54); age-focused OR 2.29 (95% CI 1.20, 4.39); and hospital diagnosis OR 1.94 (95% CI 1.01, 3.72). CONCLUSIONS: Each definition yielded an estimate of the association in the direction of increased risk of HUS with antibiotics. While the range of OR point estimates was relatively small, confidence intervals for two HUS definitions crossed the null and two did not, potentially altering the inference an investigator makes. Discrepant reports of the association between antibiotic use and HUS in the literature might be due in part to the choice of HUS definition, and a consistent definition of HUS should be adopted for research and public health purposes.
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Antibacterianos/efectos adversos , Antibacterianos/uso terapéutico , Infecciones por Escherichia coli/complicaciones , Infecciones por Escherichia coli/tratamiento farmacológico , Escherichia coli O157/aislamiento & purificación , Síndrome Hemolítico-Urémico/etiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Diagnóstico Diferencial , Infecciones por Escherichia coli/epidemiología , Femenino , Síndrome Hemolítico-Urémico/inducido químicamente , Síndrome Hemolítico-Urémico/diagnóstico , Síndrome Hemolítico-Urémico/epidemiología , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Guías de Práctica Clínica como Asunto , Estudios Retrospectivos , Washingtón/epidemiología , Adulto JovenRESUMEN
The often-noted and persistent increased incidence of Escherichia coli O157:H7 infections in rural areas is not well understood. We used a cohort of E. coli O157:H7 cases reported in Washington, USA, during 2005-2014, along with phylogenomic characterization of the infecting isolates, to identify geographic segregation of and temporal trends in specific phylogenetic lineages of E. coli O157:H7. Kernel estimation and generalized additive models demonstrated that pathogen lineages were spatially segregated during the period of analysis and identified a focus of segregation spanning multiple, predominantly rural, counties for each of the main clinical lineages, Ib, IIa, and IIb. These results suggest the existence of local reservoirs from which humans are infected. We also noted a secular increase in the proportion of lineage IIa and IIb isolates. Spatial segregation by phylogenetic lineage offers the potential to identify local reservoirs and intervene to prevent continued transmission.