ABSTRACT
BACKGROUND: The US' coronavirus disease 2019 (COVID-19) epidemic has grown extensively since February 2020, with substantial associated hospitalizations and mortality; New York State has emerged as the national epicenter. We report on the extent of testing and test results during the month of March in New York State, along with risk factors, outcomes, and household prevalence among initial cases subject to in-depth investigations. METHODS: Specimen collection for COVID-19 testing was conducted in healthcare settings, community-based collection sites, and by home testing teams. Information on demographics, risk factors, and hospital outcomes of cases was obtained through epidemiological investigations and an electronic medical records match, and summarized descriptively. Active testing of initial case's households enabled estimation of household prevalence. RESULTS: During March in New York State, outside of New York City, a total of 47â 326 persons tested positive for severe acute respiratory syndrome coronavirus 2, out of 141â 495 tests (33% test-positive), with the highest number of cases located in the metropolitan region counties. Among 229 initial cases diagnosed through 12 March, by 30 March 13% were hospitalized and 2% died. Testing conducted among 498 members of these case's households found prevalent infection among 57%, excluding first-reported cases 38%. In these homes, we found a significant age gradient in prevalence, from 23% among thoseâ <â 5 years to 68% among thoseâ ≥â 65 years (Pâ <â .0001). CONCLUSIONS: New York State faced a substantial and increasing COVID-19 outbreak during March 2020. The earliest cases had high levels of infection in their households and by the end of the month, the risks of hospitalization and death were high.
Subject(s)
Clinical Laboratory Techniques/statistics & numerical data , Coronavirus Infections/epidemiology , Family Characteristics , Hospitalization/statistics & numerical data , Pneumonia, Viral/epidemiology , Adolescent , Adult , Age Distribution , Aged , COVID-19 , COVID-19 Testing , Child , Child, Preschool , Coronavirus Infections/diagnosis , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , New York/epidemiology , Pandemics , Prevalence , Risk Factors , Spatial Analysis , Young AdultABSTRACT
Importance: Hydroxychloroquine, with or without azithromycin, has been considered as a possible therapeutic agent for patients with coronavirus disease 2019 (COVID-19). However, there are limited data on efficacy and associated adverse events. Objective: To describe the association between use of hydroxychloroquine, with or without azithromycin, and clinical outcomes among hospital inpatients diagnosed with COVID-19. Design, Setting, and Participants: Retrospective multicenter cohort study of patients from a random sample of all admitted patients with laboratory-confirmed COVID-19 in 25 hospitals, representing 88.2% of patients with COVID-19 in the New York metropolitan region. Eligible patients were admitted for at least 24 hours between March 15 and 28, 2020. Medications, preexisting conditions, clinical measures on admission, outcomes, and adverse events were abstracted from medical records. The date of final follow-up was April 24, 2020. Exposures: Receipt of both hydroxychloroquine and azithromycin, hydroxychloroquine alone, azithromycin alone, or neither. Main Outcomes and Measures: Primary outcome was in-hospital mortality. Secondary outcomes were cardiac arrest and abnormal electrocardiogram findings (arrhythmia or QT prolongation). Results: Among 1438 hospitalized patients with a diagnosis of COVID-19 (858 [59.7%] male, median age, 63 years), those receiving hydroxychloroquine, azithromycin, or both were more likely than those not receiving either drug to have diabetes, respiratory rate >22/min, abnormal chest imaging findings, O2 saturation lower than 90%, and aspartate aminotransferase greater than 40 U/L. Overall in-hospital mortality was 20.3% (95% CI, 18.2%-22.4%). The probability of death for patients receiving hydroxychloroquine + azithromycin was 189/735 (25.7% [95% CI, 22.3%-28.9%]), hydroxychloroquine alone, 54/271 (19.9% [95% CI, 15.2%-24.7%]), azithromycin alone, 21/211 (10.0% [95% CI, 5.9%-14.0%]), and neither drug, 28/221 (12.7% [95% CI, 8.3%-17.1%]). In adjusted Cox proportional hazards models, compared with patients receiving neither drug, there were no significant differences in mortality for patients receiving hydroxychloroquine + azithromycin (HR, 1.35 [95% CI, 0.76-2.40]), hydroxychloroquine alone (HR, 1.08 [95% CI, 0.63-1.85]), or azithromycin alone (HR, 0.56 [95% CI, 0.26-1.21]). In logistic models, compared with patients receiving neither drug cardiac arrest was significantly more likely in patients receiving hydroxychloroquine + azithromycin (adjusted OR, 2.13 [95% CI, 1.12-4.05]), but not hydroxychloroquine alone (adjusted OR, 1.91 [95% CI, 0.96-3.81]) or azithromycin alone (adjusted OR, 0.64 [95% CI, 0.27-1.56]), . In adjusted logistic regression models, there were no significant differences in the relative likelihood of abnormal electrocardiogram findings. Conclusions and Relevance: Among patients hospitalized in metropolitan New York with COVID-19, treatment with hydroxychloroquine, azithromycin, or both, compared with neither treatment, was not significantly associated with differences in in-hospital mortality. However, the interpretation of these findings may be limited by the observational design.
Subject(s)
Anti-Infective Agents/therapeutic use , Azithromycin/therapeutic use , Coronavirus Infections/drug therapy , Hospital Mortality , Hydroxychloroquine/therapeutic use , Pneumonia, Viral/drug therapy , Adolescent , Adult , Aged , Anti-Infective Agents/adverse effects , Arrhythmias, Cardiac/chemically induced , Azithromycin/adverse effects , Betacoronavirus , COVID-19 , Coronavirus Infections/mortality , Drug Therapy, Combination , Female , Heart Arrest/etiology , Hospitalization , Humans , Hydroxychloroquine/adverse effects , Logistic Models , Male , Middle Aged , New York , Pandemics , Pneumonia, Viral/mortality , Proportional Hazards Models , Retrospective Studies , SARS-CoV-2 , Young Adult , COVID-19 Drug TreatmentABSTRACT
It has been repeatedly shown that the heavy metal mercury can induce or exacerbate lupus like autoimmunity in susceptible strains of rats and mice. A hallmark of such autoimmune induction is the accompaniment of an immune shift, in which there is usually an initial skewing toward a Th2-like immune environment. Another heavy metal, lead (Pb), has also been found to induce a Th2 shift in mice. However, exposure of normal mouse strains to Pb does not appear to induce autoimmunity. In order to investigate whether mice genetically predisposed to murine systemic lupus erythematosus (SLE) are susceptible to a Pb-induced exacerbation of lupus, males and females of four New Zealand mixed (NZM) mouse strains, along with BALB/c and C57Bl/6 controls, were administered three 100-microliter intraperitoneal injections of either 1.31 mM lead or sodium acetate per week for 3 wk. The four NZM strains chosen, NZM391, NZM2328, NZM88, and NZM2758, have differential genetic penetrance for SLE with variances in certain manifestations of the disease, but all of these strains naturally develop glomerulonephritis and produce high titers of anti-nuclear autoantibodies. The mice were prebled for baseline values and were bled directly after the injection period (d 1) and monthly thereafter for 5 mo. Sera were assessed for anti-double-stranded DNA titers, urea nitrogen levels, and creatine kinase activity, as well as four total immunoglobulin (Ig) G2a and IgG1 levels. Mortality and morbidity of the mice were also recorded. All NZM strains showed an acute, non-gender-based, susceptibility to Pb at d 1, but the control strains were unaffected. Over time, it became apparent that the strains diverged: The NZM391 strain showed gender-independent susceptibility to Pb enhancement of lupus manifestations and mortality; the NZM2328 strain exhibited gender-independent Pb susceptibility to manifestations, although only females had increased mortality; the NZM2758 strain exhibited non-gender-based elevations in urea nitrogen and creatine kinase activity levels; and the NZM88 strain displayed male susceptibility to anti-DNA and life span. Surprisingly, Pb increased the longevity of NZM88 and NZM2758 females. These results indicate that Pb indeed can exacerbate SLE in lupus-prone mice; however, even among lupus-prone strains, genetic differences determine the degree of exacerbation. Using the known phenotype and genetic differences, one can identify and characterize possible traits and loci associated with Pb susceptibility.
Subject(s)
Genetic Predisposition to Disease , Lead/toxicity , Lupus Erythematosus, Systemic/genetics , Analysis of Variance , Animals , Antibodies, Antinuclear/blood , Blood Urea Nitrogen , Creatine Kinase/blood , DNA/immunology , Disease Models, Animal , Female , Growth Hormone/blood , Immunoglobulin G/blood , Longevity/drug effects , Longevity/genetics , Lupus Erythematosus, Systemic/blood , Lupus Erythematosus, Systemic/immunology , Male , Mice , Mice, Inbred BALB C/genetics , Mice, Inbred C57BL/genetics , Mice, Inbred NZB/genetics , Organometallic Compounds/administration & dosage , Reference Values , Sex FactorsSubject(s)
Animal Welfare , Breeding/methods , Dogs/physiology , Selection, Genetic , Animals , Dogs/genetics , Female , MaleSubject(s)
Animal Welfare , Euthanasia, Animal/methods , Poultry , Animal Welfare/legislation & jurisprudence , Animals , Cervical Vertebrae/injuries , Craniocerebral Trauma/veterinary , Decapitation/veterinary , Euthanasia, Animal/ethics , Euthanasia, Animal/legislation & jurisprudence , Joint Dislocations/veterinaryABSTRACT
Where research on one species is justified on the grounds that it will provide benefits to another, the strength of the ethical case depends critically on whether findings can be extrapolated meaningfully. Valid extrapolation depends on the species being sufficiently similar in respects critical to the research and on knowledge of the bases and effects of salient differences. Many biological parameters vary with body weight (W) between species. When species of small size are used to model larger ones, the influence of size on the rates of physiological, immunological and other processes must be taken into account. Between species, the rates of physiological processes tend to increase with W(0.75), and the durations of physiological events tend to increase with W(0.25). Providing potential pitfalls are understood, allometric scaling enables valid comparisons and extrapolations between species. Knowledge of these principles is crucial also in making predictions about many aspects of animals' biology and has application also in making sound ethical judgments about the justifiability of extrapolations between species concerning the wide range of processes linked to rates of metabolism.
Subject(s)
Ethics , Models, Animal , Species Specificity , Animals , Predictive Value of Tests , Reproducibility of ResultsABSTRACT
The importance of wild bird populations as a reservoir of zoonotic pathogens is well established. Salmonellosis is a frequently diagnosed infectious cause of mortality of garden birds in England and Wales, predominantly caused by Salmonella enterica subspecies enterica serovar Typhimurium definitive phage types 40, 56(v) and 160. In Britain, these phage types are considered highly host-adapted with a high degree of genetic similarity amongst isolates, and in some instances are clonal. Pulsed field gel electrophoresis, however, demonstrated minimal variation amongst matched DT40 and DT56(v) isolates derived from passerine and human incidents of salmonellosis across England in 2000-2007. Also, during the period 1993-2012, similar temporal and spatial trends of infection with these S. Typhimurium phage types occurred in both the British garden bird and human populations; 1.6% of all S. Typhimurium (0.2% of all Salmonella) isolates from humans in England and Wales over the period 2000-2010. These findings support the hypothesis that garden birds act as the primary reservoir of infection for these zoonotic bacteria. Most passerine salmonellosis outbreaks identified occurred at and around feeding stations, which are likely sites of public exposure to sick or dead garden birds and their faeces. We, therefore, advise the public to practise routine personal hygiene measures when feeding wild birds and especially when handling sick wild birds.
Subject(s)
Bird Diseases/transmission , Salmonella Infections/transmission , Salmonella typhimurium/isolation & purification , Zoonoses/epidemiology , Animals , Bird Diseases/epidemiology , Bird Diseases/microbiology , Birds , Electrophoresis, Gel, Pulsed-Field , England/epidemiology , Humans , Salmonella Infections/epidemiology , Wales/epidemiologyABSTRACT
Finch trichomonosis emerged in Great Britain in 2005 and led to epidemic mortality and a significant population decline of greenfinches, Carduelis chloris and chaffinches, Fringilla coelebs, in the central and western counties of England and Wales in the autumn of 2006. In this article, we show continued epidemic spread of the disease with a pronounced shift in geographical distribution towards eastern England in 2007. This was followed by international spread to southern Fennoscandia where cases were confirmed at multiple sites in the summer of 2008. Sequence data of the ITS1/5.8S/ITS2 ribosomal region and part of the small subunit (SSU) rRNA gene showed no variation between the British and Fennoscandian parasite strains of Trichomonas gallinae. Epidemiological and historical ring return data support bird migration as a plausible mechanism for the observed pattern of disease spread, and suggest the chaffinch as the most likely primary vector. This finding is novel since, although intuitive, confirmed disease spread by migratory birds is very rare and, when it has been recognised, this has generally been for diseases caused by viral pathogens. We believe this to be the first documented case of the spread of a protozoal emerging infectious disease by migrating birds.
Subject(s)
Animal Migration , Bird Diseases/epidemiology , Communicable Diseases, Emerging/veterinary , Finches/parasitology , Trichomonas Infections/veterinary , Animals , Base Sequence , Bird Diseases/parasitology , Bird Diseases/transmission , Communicable Diseases, Emerging/epidemiology , Communicable Diseases, Emerging/transmission , Disease Outbreaks/veterinary , Female , Male , Space-Time Clustering , Trichomonas/isolation & purification , Trichomonas/pathogenicity , Trichomonas Infections/epidemiology , Trichomonas Infections/transmission , United Kingdom/epidemiologySubject(s)
Animals, Laboratory , Transportation/methods , Amphibians , Animal Welfare , Animals , Cats , Dogs , Drinking , Eating , Female , Ferrets , Pregnancy , Primates , Professional Competence , Rabbits , Rodentia , Swine , Swine, Miniature , Transportation/instrumentation , Transportation/legislation & jurisprudence , XenopusSubject(s)
Animal Welfare , Euthanasia, Animal/ethics , Veterinary Medicine/ethics , Animals , Humans , Quality of LifeABSTRACT
Emerging infectious diseases are increasingly cited as threats to wildlife, livestock and humans alike. They can threaten geographically isolated or critically endangered wildlife populations; however, relatively few studies have clearly demonstrated the extent to which emerging diseases can impact populations of common wildlife species. Here, we report the impact of an emerging protozoal disease on British populations of greenfinch Carduelis chloris and chaffinch Fringilla coelebs, two of the most common birds in Britain. Morphological and molecular analyses showed this to be due to Trichomonas gallinae. Trichomonosis emerged as a novel fatal disease of finches in Britain in 2005 and rapidly became epidemic within greenfinch, and to a lesser extent chaffinch, populations in 2006. By 2007, breeding populations of greenfinches and chaffinches in the geographic region of highest disease incidence had decreased by 35% and 21% respectively, representing mortality in excess of half a million birds. In contrast, declines were less pronounced or absent in these species in regions where the disease was found in intermediate or low incidence. Also, populations of dunnock Prunella modularis, which similarly feeds in gardens, but in which T. gallinae was rarely recorded, did not decline. This is the first trichomonosis epidemic reported in the scientific literature to negatively impact populations of free-ranging non-columbiform species, and such levels of mortality and decline due to an emerging infectious disease are unprecedented in British wild bird populations. This disease emergence event demonstrates the potential for a protozoan parasite to jump avian host taxonomic groups with dramatic effect over a short time period.
Subject(s)
Bird Diseases/epidemiology , Birds , Communicable Diseases/veterinary , Animals , Base Sequence , Bird Diseases/parasitology , Birds/parasitology , Data Collection , Disease Outbreaks , Female , Male , Population Dynamics , Time Factors , Trichomonadida/genetics , Trichomonadida/physiologySubject(s)
Animal Husbandry/methods , Dogs , Mice , Primates , Rats , Telemetry/veterinary , Animal Husbandry/standards , Animal Welfare , Animals , Animals, Laboratory , Surgery, VeterinaryABSTRACT
Phenotypic and phylogenetic studies were performed on three strains of Gram-negative, rod-shaped organisms recovered from dead birds of the tit families (blue tit, coal tit and long-tailed tit). Morphological, cultural and biochemical studies indicated that the organisms were related to the family Cardiobacteriaceae in the gamma-subclass of the Proteobacteria. Comparative 16S rRNA gene sequencing studies confirmed these findings and demonstrated that the bacterium represents a hitherto unknown subline within this family. The closest phylogenetic relative of the strains isolated from the birds was found to be Suttonella indologenes, although a sequence divergence of approximately 5 % demonstrated that the unknown bacterium represented a novel species. On the basis of the results of the phylogenetic analysis and phenotypic criteria, it is proposed that the bacteria recovered from the diseased birds represent a novel species, Suttonella ornithocola sp. nov., with strain B6/99/2T (=CCUG 49457T=NCTC 13337T) as the type strain.
Subject(s)
Birds/microbiology , Cardiobacteriaceae/classification , RNA, Ribosomal, 16S/analysis , Animals , Cardiobacteriaceae/genetics , Molecular Sequence Data , Phenotype , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNAABSTRACT
Of all the species exposed naturally to the bovine spongiform encephalopathy (BSE) agent, the greater kudu (Tragelaphus strepsiceros), a nondomesticated bovine from Africa, appears to be the most susceptible to the disease. We present the results of mouse bioassay studies to show that, contrary to findings in cattle with BSE in which the tissue distribution of infectivity is the most limited recorded for any of the transmissible spongiform encephalopathies (TSE), infectivity in greater kudu with BSE is distributed in as wide a range of tissues as occurs in any TSE. BSE agent was also detected in skin, conjunctiva, and salivary gland, tissues in which infectivity has not previously been reported in any naturally occurring TSE. The distribution of infectivity in greater kudu with BSE suggests possible routes for transmission of the disease and highlights the need for further research into the distribution of TSE infectious agents in other host species.