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1.
Nat Commun ; 13(1): 3645, 2022 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-35752633

RESUMO

Recombination is an evolutionary process by which many pathogens generate diversity and acquire novel functions. Although a common occurrence during coronavirus replication, detection of recombination is only feasible when genetically distinct viruses contemporaneously infect the same host. Here, we identify an instance of SARS-CoV-2 superinfection, whereby an individual was infected with two distinct viral variants: Alpha (B.1.1.7) and Epsilon (B.1.429). This superinfection was first noted when an Alpha genome sequence failed to exhibit the classic S gene target failure behavior used to track this variant. Full genome sequencing from four independent extracts reveals that Alpha variant alleles comprise around 75% of the genomes, whereas the Epsilon variant alleles comprise around 20% of the sample. Further investigation reveals the presence of numerous recombinant haplotypes spanning the genome, specifically in the spike, nucleocapsid, and ORF 8 coding regions. These findings support the potential for recombination to reshape SARS-CoV-2 genetic diversity.


Assuntos
COVID-19 , Superinfecção , Genoma Viral/genética , Humanos , Cidade de Nova Iorque/epidemiologia , Recombinação Genética , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética
2.
Diagn Microbiol Infect Dis ; 101(3): 115468, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34425451

RESUMO

Nasal and nasopharyngeal swab specimens tested by the Cepheid Xpert Xpress SARS-CoV-2 were analyzed by whole-genome sequencing based on impaired detection of the N2 target. Each viral genome had at least one mutation in the N gene, which likely arose independently in the New York City and Pittsburgh study sites.


Assuntos
COVID-19/epidemiologia , COVID-19/virologia , Proteínas do Nucleocapsídeo de Coronavírus/genética , SARS-CoV-2/genética , Cidades/epidemiologia , Bases de Dados Genéticas , Genoma Viral , Humanos , Mutação , Fosfoproteínas/genética , Estados Unidos/epidemiologia
3.
Nat Commun ; 12(1): 4886, 2021 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-34373458

RESUMO

Wide-scale SARS-CoV-2 genome sequencing is critical to tracking viral evolution during the ongoing pandemic. We develop the software tool, Variant Database (VDB), for quickly examining the changing landscape of spike mutations. Using VDB, we detect an emerging lineage of SARS-CoV-2 in the New York region that shares mutations with previously reported variants. The most common sets of spike mutations in this lineage (now designated as B.1.526) are L5F, T95I, D253G, E484K or S477N, D614G, and A701V. This lineage was first sequenced in late November 2020. Phylodynamic inference confirmed the rapid growth of the B.1.526 lineage. In concert with other variants, like B.1.1.7, the rise of B.1.526 appears to have extended the duration of the second wave of COVID-19 cases in NYC in early 2021. Pseudovirus neutralization experiments demonstrated that B.1.526 spike mutations adversely affect the neutralization titer of convalescent and vaccinee plasma, supporting the public health relevance of this lineage.


Assuntos
COVID-19/virologia , SARS-CoV-2/classificação , SARS-CoV-2/isolamento & purificação , COVID-19/epidemiologia , Genoma Viral , Humanos , Modelos Moleculares , Mutação , New York/epidemiologia , Filogenia , SARS-CoV-2/genética , Software , Glicoproteína da Espícula de Coronavírus/genética
4.
Am J Clin Pathol ; 156(3): 370-380, 2021 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-34302455

RESUMO

OBJECTIVES: The Abbot ID NOW COVID-19 assay and Quidel Sofia 2 SARS Antigen FIA are point-of-care assays that offer rapid testing for severe acute respiratory syndrome coronavirus 2 viral RNA and nucleocapsid protein, respectively. Given the utility of these devices in the field, we investigated the feasibility and safety of using the ID NOW and Sofia assays in the public health response to the coronavirus disease 2019 pandemic and in future public health emergencies. METHODS: A combination of utilization and contamination testing in addition to a review of instrument workflows was conducted. RESULTS: Utilization testing demonstrated that both tests are intuitive, associated with high user test success (85%) in our study, and could be implemented by staff after minimal training. Contamination tests revealed potential biosafety concerns due to the open design of the ID NOW instrument and the transfer mechanisms with the Sofia. When comparing the workflow of the ID NOW and the Sofia, we found that the ID NOW was more user-friendly and that the transfer technology reduces the chance of contamination. CONCLUSIONS: The ID NOW, Sofia, and other emerging point-of-care tests should be used only after careful consideration of testing workflow, biosafety risk mitigations, and appropriate staff training.


Assuntos
Antígenos Virais/análise , Teste para COVID-19 , COVID-19/diagnóstico , Pandemias , Testes Imediatos , SARS-CoV-2/imunologia , COVID-19/epidemiologia , COVID-19/virologia , Contenção de Riscos Biológicos , Segurança de Equipamentos , Estudos de Viabilidade , Humanos , Medição de Risco , SARS-CoV-2/isolamento & purificação
5.
J Infect Dis ; 224(2): 188-195, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34086923

RESUMO

BACKGROUND: Serosurveys help to ascertain burden of infection. Prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serosurveys in New York City (NYC) used nonrandom samples. During June-October 2020, the NYC Health Department conducted a population-based survey estimating SARS-CoV-2 antibody prevalence in NYC adults. METHODS: Participants were recruited from the NYC 2020 Community Health Survey. We estimated citywide and stratified antibody prevalence using a hybrid design: serum tested with the DiaSorin LIAISON SARS-CoV-2 S1/S2 IgG assay and self-reported antibody test results were used together. We estimated univariate frequencies and 95% confidence intervals (CI), accounting for complex survey design. Two-sided P values ≤ .05 were statistically significant. RESULTS: There were 1074 respondents; 497 provided blood and 577 provided only a self-reported antibody test result. Weighted prevalence was 24.3% overall (95% CI, 20.7%-28.3%). Latino (30.7%; 95% CI, 24.1%-38.2%; P < .01) and black (30.7%; 95% CI, 21.9%-41.2%; P = .02) respondents had a higher weighted prevalence compared with white respondents (17.4%; 95% CI, 12.5%-23.7%). CONCLUSIONS: By October 2020, nearly 1 in 3 black and 1 in 3 Latino NYC adults had SARS-CoV-2 antibodies, highlighting unequal impacts of the coronavirus disease 2019 (COVID-19) pandemic on black and Latino NYC adults.


Assuntos
Anticorpos Antivirais/sangue , SARS-CoV-2/imunologia , Adolescente , Adulto , Idoso , COVID-19/epidemiologia , Etnicidade/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque/epidemiologia , Prevalência , Estudos Soroepidemiológicos , Adulto Jovem
6.
PLoS One ; 16(6): e0252949, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34170927

RESUMO

To address the need for simple, safe, sensitive, and scalable SARS-CoV-2 tests, we validated and implemented a PCR test that uses a saliva collection kit use at home. Individuals self-collected 300 µl saliva in vials containing Darnell Rockefeller University Laboratory (DRUL) buffer and extracted RNA was assayed by RT-PCR (the DRUL saliva assay). The limit of detection was confirmed to be 1 viral copy/µl in 20 of 20 replicate extractions. Viral RNA was stable in DRUL buffer at room temperature up to seven days after sample collection, and safety studies demonstrated that DRUL buffer immediately inactivated virus at concentrations up to 2.75x106 PFU/ml. Results from SARS-CoV-2 positive nasopharyngeal (NP) swab samples collected in viral transport media and assayed with a standard FDA Emergency Use Authorization (EUA) test were highly correlated with samples placed in DRUL buffer. Direct comparison of results from 162 individuals tested by FDA EUA oropharyngeal (OP) or NP swabs with co-collected saliva samples identified four otherwise unidentified positive cases in DRUL buffer. Over six months, we collected 3,724 samples from individuals ranging from 3 months to 92 years of age. This included collecting weekly samples over 10 weeks from teachers, children, and parents from a pre-school program, which allowed its safe reopening while at-risk pods were quarantined. In sum, we validated a simple, sensitive, stable, and safe PCR-based test using a self-collected saliva sample as a valuable tool for clinical diagnosis and screening at workplaces and schools.


Assuntos
Teste de Ácido Nucleico para COVID-19 , COVID-19 , SARS-CoV-2 , Saliva/virologia , Instituições Acadêmicas , Manejo de Espécimes , COVID-19/diagnóstico , COVID-19/genética , Criança , Feminino , Humanos , Masculino
7.
MMWR Morb Mortal Wkly Rep ; 70(19): 712-716, 2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-33983915

RESUMO

Recent studies have documented the emergence and rapid growth of B.1.526, a novel variant of interest (VOI) of SARS-CoV-2, the virus that causes COVID-19, in the New York City (NYC) area after its identification in NYC in November 2020 (1-3). Two predominant subclades within the B.1.526 lineage have been identified, one containing the E484K mutation in the receptor-binding domain (1,2), which attenuates in vitro neutralization by multiple SARS-CoV-2 antibodies and is present in variants of concern (VOCs) first identified in South Africa (B.1.351) (4) and Brazil (P.1).* The NYC Department of Health and Mental Hygiene (DOHMH) analyzed laboratory and epidemiologic data to characterize cases of B.1.526 infection, including illness severity, transmission to close contacts, rates of possible reinfection, and laboratory-diagnosed breakthrough infections among vaccinated persons. Preliminary data suggest that the B.1.526 variant does not lead to more severe disease and is not associated with increased risk for infection after vaccination (breakthrough infection) or reinfection. Because relatively few specimens were sequenced over the study period, the statistical power might have been insufficient to detect modest differences in rates of uncommon outcomes such as breakthrough infection or reinfection. Collection of timely viral genomic data for a larger proportion of citywide cases and rapid integration with population-based surveillance data would enable improved understanding of the impact of emerging SARS-CoV-2 variants and specific mutations to help guide public health intervention efforts.


Assuntos
COVID-19/epidemiologia , COVID-19/virologia , SARS-CoV-2/genética , Adolescente , Adulto , Idoso , Teste de Ácido Nucleico para COVID-19 , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque/epidemiologia , Adulto Jovem
8.
bioRxiv ; 2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33907745

RESUMO

Wide-scale SARS-CoV-2 genome sequencing is critical to tracking viral evolution during the ongoing pandemic. Variants first detected in the United Kingdom, South Africa, and Brazil have spread to multiple countries. We developed the software tool, Variant Database (VDB), for quickly examining the changing landscape of spike mutations. Using VDB, we detected an emerging lineage of SARS-CoV-2 in the New York region that shares mutations with previously reported variants. The most common sets of spike mutations in this lineage (now designated as B.1.526) are L5F, T95I, D253G, E484K or S477N, D614G, and A701V. This lineage was first sequenced in late November 2020 when it represented <1% of sequenced coronavirus genomes that were collected in New York City (NYC). By February 2021, genomes from this lineage accounted for ~32% of 3288 sequenced genomes from NYC specimens. Phylodynamic inference confirmed the rapid growth of the B.1.526 lineage in NYC, notably the sub-clade defined by the spike mutation E484K, which has outpaced the growth of other variants in NYC. Pseudovirus neutralization experiments demonstrated that B.1.526 spike mutations adversely affect the neutralization titer of convalescent and vaccinee plasma, indicating the public health importance of this lineage.

9.
J Clin Microbiol ; 59(4)2021 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-32999007

RESUMO

Rapid and reliable detection of rifampin (RIF) resistance is critical for the diagnosis and treatment of drug-resistant and multidrug-resistant (MDR) tuberculosis. Discordant RIF phenotype/genotype susceptibility results remain a challenge due to the presence of rpoB mutations that do not confer high levels of RIF resistance, as have been exhibited in strains with mutations such as Ser450Leu. These strains, termed low-level RIF resistant, exhibit elevated RIF MICs compared to fully susceptible strains but remain phenotypically susceptible by mycobacterial growth indicator tube (MGIT) testing and have been associated with poor patient outcomes. Here, we assess RIF resistance prediction by whole-genome sequencing (WGS) among a set of 1,779 prospectively tested strains by both prevalence of rpoB gene mutation and phenotype as part of routine clinical testing during a 2.5-year period. During this time, 139 strains were found to have nonsynonymous rpoB mutations, 53 of which were associated with RIF resistance, including both low-level and high-level resistance. Resistance to RIF (1.0 µg/ml in MGIT) was identified in 43 (81.1%) isolates. The remaining 10 (18.9%) strains were susceptible by MGIT but were confirmed to be low-level RIF resistant by MIC testing. Full rpoB gene sequencing overcame the limitations of critical concentration phenotyping, probe-based genotyping, and partial gene sequencing methods. Universal clinical WGS with concurrent phenotypic testing provided a more complete understanding of the prevalence and type of rpoB mutations and their association with RIF resistance in New York.


Assuntos
Mycobacterium tuberculosis , Preparações Farmacêuticas , Tuberculose Resistente a Múltiplos Medicamentos , Antituberculosos/farmacologia , Proteínas de Bactérias/genética , RNA Polimerases Dirigidas por DNA/genética , Farmacorresistência Bacteriana/genética , Humanos , Testes de Sensibilidade Microbiana , Mutação , Mycobacterium tuberculosis/genética , New York , Rifampina/farmacologia
10.
Clin Infect Dis ; 73(9): e3146-e3155, 2021 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-32829411

RESUMO

BACKGROUND: Genomic epidemiology studies of gonorrhea in the United States have primarily focused on national surveillance for antibiotic resistance, and patterns of local transmission between demographic groups of resistant and susceptible strains are unknown. METHODS: We analyzed a convenience sample of genome sequences, antibiotic susceptibility, and patient data from 897 gonococcal isolates cultured at the New York City (NYC) Public Health Laboratory from NYC Department of Health and Mental Hygiene (DOHMH) Sexual Health Clinic (SHC) patients, primarily in 2012-2013. We reconstructed the gonococcal phylogeny, defined transmission clusters using a 10 nonrecombinant single nucleotide polymorphism threshold, tested for clustering of demographic groups, and placed NYC isolates in a global phylogenetic context. RESULTS: The NYC gonococcal phylogeny reflected global diversity with isolates from 22/23 of the prevalent global lineages (96%). Isolates clustered on the phylogeny by patient sexual behavior (P < .001) and race/ethnicity (P < .001). Minimum inhibitory concentrations were higher across antibiotics in isolates from men who have sex with men compared to heterosexuals (P < .001) and white heterosexuals compared to black heterosexuals (P < .01). In our dataset, all large transmission clusters (≥10 samples) of N. gonorrhoeae were susceptible to ciprofloxacin, ceftriaxone, and azithromycin, and comprised isolates from patients across demographic groups. CONCLUSIONS: All large transmission clusters were susceptible to gonorrhea therapies, suggesting that resistance to empiric therapy was not a main driver of spread, even as risk for resistance varied across demographic groups. Further study of local transmission networks is needed to identify drivers of transmission.


Assuntos
Gonorreia , Minorias Sexuais e de Gênero , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Azitromicina/farmacologia , Demografia , Farmacorresistência Bacteriana , Gonorreia/tratamento farmacológico , Gonorreia/epidemiologia , Homossexualidade Masculina , Humanos , Masculino , Testes de Sensibilidade Microbiana , Neisseria gonorrhoeae/genética , Filogenia
11.
J Clin Microbiol ; 59(3)2021 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-33298613

RESUMO

With the approach of respiratory virus season in the Northern Hemisphere, clinical microbiology and public health laboratories will need rapid diagnostic assays to distinguish severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from influenza virus and respiratory syncytial virus (RSV) infections for diagnosis and surveillance. In this study, the clinical performance of the Xpert Xpress SARS-CoV-2/Flu/RSV test (Cepheid, Sunnyvale, CA, USA) for nasopharyngeal swab specimens was evaluated in four centers: Johns Hopkins Medical Microbiology Laboratory, Northwell Health Laboratories, NYC Public Health Laboratory, and Los Angeles County/University of Southern California (LAC+USC) Medical Center. A total of 319 nasopharyngeal swab specimens, positive for SARS-CoV-2 (n = 75), influenza A virus (n = 65), influenza B virus (n = 50), or RSV (n = 38) or negative (n = 91) by the standard-of-care nucleic acid amplification tests at each site, were tested using the Cepheid panel test. The overall positive percent agreement for the SARS-CoV-2 target was 98.7% (n = 74/75), and the negative agreement was 100% (n = 91), with all other analytes showing 100% total agreement (n = 153). Standard-of-care tests to which the Cepheid panel was compared included the Cepheid Xpert Xpress SARS-CoV-2, Cepheid Xpert Xpress Flu/RSV, GenMark ePlex respiratory panel, BioFire respiratory panel 2.1 and v1.7, DiaSorin Simplexa COVID-19 Direct, and Hologic Panther Fusion SARS-CoV-2 assays. The Xpert Xpress SARS-CoV-2/Flu/RSV test showed high sensitivity and accuracy for all analytes included in the test. This test will provide a valuable clinical diagnostic and public health solution for detecting and differentiating SARS-CoV-2, influenza A and B virus, and RSV infections during the current respiratory virus season.


Assuntos
COVID-19/diagnóstico , Influenza Humana/diagnóstico , Técnicas de Diagnóstico Molecular/métodos , Humanos , Nasofaringe , SARS-CoV-2 , Sensibilidade e Especificidade
12.
J Clin Microbiol ; 58(8)2020 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-32366669

RESUMO

Nucleic acid amplification tests (NAATs) are the primary means of identifying acute infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Accurate and fast test results may permit more efficient use of protective and isolation resources and allow rapid therapeutic interventions. We evaluated the analytical and clinical performance characteristics of the Xpert Xpress SARS-CoV-2 (Xpert) test, a rapid, automated molecular test for SARS-CoV-2. Analytical sensitivity and specificity/interference were assessed with infectious SARS-CoV-2; other infectious coronavirus species, including SARS-CoV; and 85 nasopharyngeal swab specimens positive for other respiratory viruses, including endemic human coronaviruses (hCoVs). Clinical performance was assessed using 483 remnant upper- and lower-respiratory-tract specimens previously analyzed by standard-of-care (SOC) NAATs. The limit of detection of the Xpert test was 0.01 PFU/ml. Other hCoVs, including Middle East respiratory syndrome coronavirus, were not detected by the Xpert test. SARS-CoV, a closely related species in the subgenus Sarbecovirus, was detected by a broad-range target (E) but was distinguished from SARS-CoV-2 (SARS-CoV-2-specific N2 target). Compared to SOC NAATs, the positive agreement of the Xpert test was 219/220 (99.5%), and the negative agreement was 250/261 (95.8%). A third tie-breaker NAAT resolved all but three of the discordant results in favor the Xpert test. The Xpert test provided sensitive and accurate detection of SARS-CoV-2 in a variety of upper- and lower-respiratory-tract specimens. The high sensitivity and short time to results of approximately 45 min may impact patient management.


Assuntos
Betacoronavirus/isolamento & purificação , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Técnicas de Diagnóstico Molecular/métodos , Pneumonia Viral/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Automação Laboratorial/métodos , Betacoronavirus/genética , COVID-19 , Teste para COVID-19 , Criança , Pré-Escolar , Infecções por Coronavirus/virologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Nasofaringe/virologia , Pandemias , Pneumonia Viral/virologia , SARS-CoV-2 , Sensibilidade e Especificidade , Adulto Jovem
13.
N Engl J Med ; 382(11): 1009-1017, 2020 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-32160662

RESUMO

BACKGROUND: Measles was declared eliminated in the United States in 2000, but the risk of outbreaks owing to international importations remains. An outbreak of measles in New York City began when one unvaccinated child returned home from Israel with measles; onset of rash occurred on September 30, 2018, 9 days after the child returned home. METHODS: We investigated suspected cases of measles by conducting interviews, reviewing medical and immunization records, identifying exposed persons, and performing diagnostic testing. Measles-mumps-rubella (MMR) vaccine (given as either MMR or measles-mumps-rubella-varicella vaccine and collectively referred to as MMR vaccine) uptake was monitored with the use of the Citywide Immunization Registry. The total direct cost to the New York City Department of Health and Mental Hygiene was calculated. RESULTS: A total of 649 cases of measles were confirmed, with onsets of rash occurring between September 30, 2018, and July 15, 2019. A majority of the patients (93.4%) were part of the Orthodox Jewish community, and 473 of the patients (72.9%) resided in the Williamsburg area of Brooklyn, New York. The median age was 3 years; 81.2% of the patients were 18 years of age or younger, and 85.8% of the patients with a known vaccination history were unvaccinated. Serious complications included pneumonia (in 37 patients [5.7%]) and hospitalization (in 49 patients [7.6%]); among the patients who were hospitalized, 20 (40.8%) were admitted to an intensive care unit. As a result of efforts to promote vaccination, the percentage of children in Williamsburg who received at least one dose of MMR vaccine increased from 79.5% to 91.1% among children 12 to 59 months of age. As of September 9, 2019, a total of 559 staff members at the Department of Health and Mental Hygiene (7% of the agency) had been involved in the measles response. The cost of the Department of Health and Mental Hygiene response was $8.4 million. CONCLUSIONS: Importation of measles and vaccination delays among young children led to an outbreak of measles in New York City. The outbreak response was resource intensive and caused serious illness, particularly among unvaccinated children.


Assuntos
Vacina contra Sarampo-Caxumba-Rubéola , Sarampo , Vacinação , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Surtos de Doenças , Feminino , Recursos em Saúde/economia , Hospitalização/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , Masculino , Sarampo/epidemiologia , Sarampo/prevenção & controle , Vacina contra Sarampo-Caxumba-Rubéola/administração & dosagem , Anamnese , Pessoa de Meia-Idade , Cidade de Nova Iorque/epidemiologia , Índice de Gravidade de Doença , Vacinação/estatística & dados numéricos , Adulto Jovem
14.
J Pediatric Infect Dis Soc ; 9(3): 311-319, 2020 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-31125410

RESUMO

BACKGROUND: Our goal was to characterize the epidemiology and clinical significance of congenital Zika virus (ZIKV) exposure by prospectively following a cohort of infants with possible congenital exposure through their first year of life. METHODS: We included infants born in New York City between 2016 and 2017 who had or were born to a woman who had laboratory evidence of ZIKV infection during pregnancy. We conducted provider/patient interviews and reviewed medical records to collect information about the pregnant women and, for infants, clinical and neurodevelopmental status at birth and 2, 6, and 12 months of age. RESULTS: Of the 404 infants who met inclusion criteria, most (385 [95.3%]) appeared well, whereas 19 (4.7%) had a possible ZIKV-associated birth defect. Seven had congenital ZIKV syndrome, and 12 were microcephalic without other abnormalities. Although infants with congenital ZIKV syndrome manifested clinical and neurodevelopmental sequelae during their first year of life, all 12 infants with isolated microcephaly were normocephalic and appeared well by 2 months of age. Laboratory evidence of ZIKV was detected for 22 of the infants, including 7 (31.8%) with a birth defect. Among 148 infants without a birth defect and negative/no laboratory results on ZIKV testing, and for whom information was available at 1 year, 4 presented with a developmental delay. CONCLUSIONS: Among infants with possible congenital ZIKV exposure, a small proportion had possible ZIKV-associated findings at birth or at follow-up, or laboratory evidence of ZIKV. Identifying and monitoring infants with possible ZIKV exposure requires extensive efforts by providers and public health departments. Longitudinal studies using standardized clinical and developmental assessments are needed for infants after possible congenital ZIKV exposure.


Assuntos
Microcefalia/etiologia , Complicações Infecciosas na Gravidez , Infecção por Zika virus/congênito , Zika virus , Anticorpos Antivirais/sangue , Deficiências do Desenvolvimento/etiologia , Feminino , Humanos , Imunoglobulina M/sangue , Lactente , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas , Masculino , Cidade de Nova Iorque , Gravidez , Zika virus/imunologia , Infecção por Zika virus/complicações , Infecção por Zika virus/diagnóstico
15.
J Clin Microbiol ; 58(2)2020 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-31694974

RESUMO

From 2015 to 2017, 11 confirmed brucellosis cases were reported in New York City, leading to 10 Brucella exposure risk events (Brucella events) in 7 clinical laboratories (CLs). Most patients had traveled to countries where brucellosis is endemic and presented with histories and findings consistent with brucellosis. CLs were not notified that specimens might yield a hazardous organism, as the clinicians did not consider brucellosis until they were notified that bacteremia with Brucella was suspected. In 3 Brucella events, the CLs did not suspect that slow-growing, small Gram-negative bacteria might be harmful. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), which has a limited capacity to identify biological threat agents (BTAs), was used during 4 Brucella events, which accounted for 84% of exposures. In 3 of these incidents, initial staining of liquid media showed Gram-positive rods or cocci, including some cocci in chains, suggesting streptococci. Over 200 occupational exposures occurred when the unknown isolates were manipulated and/or tested on open benches, including by procedures that could generate infectious aerosols. During 3 Brucella events, the CLs examined and/or manipulated isolates in a biological safety cabinet (BSC); in each CL, the CL had previously isolated Brucella Centers for Disease Control and Prevention recommendations to prevent laboratory-acquired brucellosis (LAB) were followed; no seroconversions or LAB cases occurred. Laboratory assessments were conducted after the Brucella events to identify facility-specific risks and mitigations. With increasing MALDI-TOF MS use, CLs are well-advised to adhere strictly to safe work practices, such as handling and manipulating all slow-growing organisms in BSCs and not using MALDI-TOF MS for identification until BTAs have been ruled out.


Assuntos
Brucella/isolamento & purificação , Brucelose/diagnóstico , Técnicas de Laboratório Clínico/normas , Infecção Laboratorial/microbiologia , Exposição Ocupacional/estatística & dados numéricos , Brucella/crescimento & desenvolvimento , Brucelose/etiologia , Contagem de Colônia Microbiana , Humanos , Cidade de Nova Iorque , Exposição Ocupacional/prevenção & controle , Fatores de Risco , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
16.
PLoS Comput Biol ; 15(9): e1007349, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31479500

RESUMO

Prediction of antibiotic resistance phenotypes from whole genome sequencing data by machine learning methods has been proposed as a promising platform for the development of sequence-based diagnostics. However, there has been no systematic evaluation of factors that may influence performance of such models, how they might apply to and vary across clinical populations, and what the implications might be in the clinical setting. Here, we performed a meta-analysis of seven large Neisseria gonorrhoeae datasets, as well as Klebsiella pneumoniae and Acinetobacter baumannii datasets, with whole genome sequence data and antibiotic susceptibility phenotypes using set covering machine classification, random forest classification, and random forest regression models to predict resistance phenotypes from genotype. We demonstrate how model performance varies by drug, dataset, resistance metric, and species, reflecting the complexities of generating clinically relevant conclusions from machine learning-derived models. Our findings underscore the importance of incorporating relevant biological and epidemiological knowledge into model design and assessment and suggest that doing so can inform tailored modeling for individual drugs, pathogens, and clinical populations. We further suggest that continued comprehensive sampling and incorporation of up-to-date whole genome sequence data, resistance phenotypes, and treatment outcome data into model training will be crucial to the clinical utility and sustainability of machine learning-based molecular diagnostics.


Assuntos
Antibacterianos/farmacologia , Genoma Bacteriano/genética , Aprendizado de Máquina , Testes de Sensibilidade Microbiana/métodos , Sequenciamento Completo do Genoma , Algoritmos , Bactérias/efeitos dos fármacos , Bactérias/genética , Infecções Bacterianas/microbiologia , Biologia Computacional , Bases de Dados Genéticas , Humanos , Reprodutibilidade dos Testes
17.
J Clin Virol ; 120: 44-50, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31557664

RESUMO

BACKGROUND: Recent emergence of Zika virus (ZIKV), and the global spread of dengue (DENV), chikungunya (CHIKV) and West Nile viruses (WNV) raised urgent need of accurate and affordable molecular diagnosis of these clinically indistinguishable arboviral infections. OBJECTIVES: We established a pentaplex real-time reverse transcription PCR (rRT-PCR) assay (CII-ArboViroPlex rRT-PCR) for specific and sensitive detection of the African and American genotypes of ZIKV, all four serotypes of DENV, CHIKV, WNV and a housekeeping gene as internal control in single reaction. STUDY DESIGN: Specific primers and probe sets were designed for ZIKV, DENV, CHIKV, WNV and RNase P (housekeeping gene) and tested for in-vitro transcribed RNA standards, virus cultures, clinical samples positive for ZIKV, DENV, CHIKV and WNV and limit of detection (LOD) were determined for each. Results Using ten-fold serially diluted in-vitro transcribed RNA, CII- ArboViroPlex rRT-PCR assay has LOD of 100 RNA copies/reaction (Rn) for ZIKV in serum or urine, 100 RNA copies/Rn for DENV in serum, and 10 RNA copies/Rn for CHIKV and WNV in serum. LODs from sera spiked with quantitated viral stocks were 2.6 × 102 GEQ/Rn for ZIKV, 2.2 × 101 GEQ/Rn for DENV-1, 9.4 × 100 GEQ/Rn for DENV-2, 2.3 × 102 GEQ/Rn for DENV-3, 1.4 × 103 GEQ/Rn for DENV-4, 2.7 × 102 GEQ/Rn for CHIKV, and 1.05 × 101 GEQ/Rn for WNV. CONCLUSIONS: The CII-ArboViroPlex rRT-PCR assay is a quantitative one-step pentaplex rRT-PCR assay for the molecular detection and differential diagnosis of ZIKV, DENV, CHIKV, WNV and a human housekeeping gene control in a single- PCR reaction.


Assuntos
Febre de Chikungunya/diagnóstico , Dengue/diagnóstico , Reação em Cadeia da Polimerase Multiplex/métodos , Febre do Nilo Ocidental/diagnóstico , Linhagem Celular , Vírus Chikungunya/genética , Vírus da Dengue/genética , Genes Essenciais , Humanos , Limite de Detecção , Técnicas de Diagnóstico Molecular/métodos , RNA Viral/sangue , RNA Viral/urina , Reação em Cadeia da Polimerase em Tempo Real , Vírus do Nilo Ocidental , Zika virus/genética , Infecção por Zika virus/diagnóstico
18.
Public Health Rep ; 134(5): 477-483, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31424330

RESUMO

During 2014-2016, the largest outbreak of Ebola virus disease (EVD) in history occurred in West Africa. The New York City Department of Health and Mental Hygiene (DOHMH) worked with health care providers to prepare for persons under investigation (PUIs) for EVD in New York City. From July 1, 2014, through December 29, 2015, we classified as a PUI a person with EVD-compatible signs or symptoms and an epidemiologic risk factor within 21 days before illness onset. Of 112 persons who met PUI criteria, 74 (66%) sought medical care and 49 (44%) were hospitalized. The remaining 38 (34%) were isolated at home with daily contact by DOHMH staff members. Thirty-two (29%) PUIs received a diagnosis of malaria. Of 10 PUIs tested, 1 received a diagnosis of EVD. Home isolation minimized unnecessary hospitalization. This case study highlights the importance of developing competency among clinical and public health staff managing persons suspected to be infected with a high-consequence pathogen.


Assuntos
Surtos de Doenças , Doença pelo Vírus Ebola/epidemiologia , Administração em Saúde Pública , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Doença pelo Vírus Ebola/diagnóstico , Doença pelo Vírus Ebola/fisiopatologia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque/epidemiologia , Vigilância da População , Medição de Risco , Adulto Jovem
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