ABSTRACT
During the 2018-2020 Ebola virus disease (EVD) outbreak in North Kivu province in the Democratic Republic of Congo, EVD was diagnosed in a patient who had received the recombinant vesicular stomatitis virus-based vaccine expressing a ZEBOV glycoprotein (rVSV-ZEBOV) (Merck). His treatment included an Ebola virus (EBOV)-specific monoclonal antibody (mAb114), and he recovered within 14 days. However, 6 months later, he presented again with severe EVD-like illness and EBOV viremia, and he died. We initiated epidemiologic and genomic investigations that showed that the patient had had a relapse of acute EVD that led to a transmission chain resulting in 91 cases across six health zones over 4 months. (Funded by the Bill and Melinda Gates Foundation and others.).
Subject(s)
Ebolavirus/genetics , Hemorrhagic Fever, Ebola/transmission , Adult , Bayes Theorem , Democratic Republic of the Congo/epidemiology , Ebola Vaccines/immunology , Ebolavirus/isolation & purification , Fatal Outcome , Genome, Viral , Hemorrhagic Fever, Ebola/diagnosis , Hemorrhagic Fever, Ebola/epidemiology , Hemorrhagic Fever, Ebola/therapy , Humans , Male , Mutation , Phylogeny , RNA, Viral/blood , RecurrenceABSTRACT
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.
Subject(s)
COVID-19 , Humans , COVID-19/epidemiology , Pandemics/prevention & control , SARS-CoV-2/genetics , Washington/epidemiology , Long-Term Care/methods , Phylogeny , GenomicsABSTRACT
BACKGROUND: Current guidelines recommend using sequential cardiac imaging to monitor for cancer treatment-related cardiac dysfunction (CTRCD) in patients undergoing potentially cardiotoxic chemotherapy. Multiple different imaging cardiac modalities are available and there are few prospective head-to-head comparative studies to help guide treatment. OBJECTIVES: To perform an exploratory prospective cohort study of "real-world" CTRCD comparing multigated acquisition nuclear ventriculography (MUGA) at the referring cancer specialist's discretion with a novel echocardiographic strategy at an Australian tertiary hospital. METHOD: Patients were recruited from haematology and oncology outpatient clinics if they were scheduled for treatment with anthracyclines and/or trastuzumab. Patients underwent simultaneous MUGA-based cardiac imaging (conventional strategy) at a frequency according to evidenced-based guidelines in addition to researcher-conducted echocardiographic imaging. The echocardiographic imaging was performed in all patients at time points recommended by international society guidelines. Outcomes included adherence to guideline recommendations, concordance between MUGA and echocardiographic left ventricular ejection fraction (LVEF) measurements, and detection of cardiac dysfunction (defined as >5% LVEF decrement from baseline by three-dimensional [3D]-LVEF). A secondary end point was accuracy of global longitudinal strain in predicting cardiac dysfunction. RESULTS: In total, 35 patients were recruited, including 15 with breast cancer, 19 with haematological malignancy, and one with gastric cancer. MUGA and echocardiographic LVEF measurements correlated poorly with limits of agreement of 30% between 3D-LVEF and MUGA-LVEF and 37% for 3D-LVEF and MUGA-LVEF. Only one case (2.9%) of CTRCD was diagnosed by MUGA, compared with 12 (34.2%) cases by echocardiography. Four (4) patients had >10% decrement in 3D-LVEF that was not detected by MUGA. Global longitudinal strain at 2 months displayed significant ability to predict CTRCD (area under the curve, 0.75, 95% confidence interval, 0.55-0.94). CONCLUSIONS: The MUGA correlates poorly with echocardiographic assessment with substantial discrepancy between MUGA and echocardiography in CTRCD diagnosis. Echocardiographic and MUGA imaging strategies should not be considered equivalent for imaging cancer patients, and a single imaging modality should ideally be used per patient to prevent misdiagnosis by inter-modality variation These findings should be considered hypothesis-generating and require confirmation with larger studies.
Subject(s)
Echocardiography , Neoplasms , Humans , Female , Male , Middle Aged , Prospective Studies , Echocardiography/methods , Neoplasms/drug therapy , Aged , Stroke Volume/physiology , Ventricular Function, Left/physiology , Predictive Value of Tests , Follow-Up Studies , AdultABSTRACT
BACKGROUND: The current study evaluated the hypothesis that the COVID-19 pandemic is associated with higher stillbirth but lower neonatal mortality rates. METHODS: We compared three epochs: baseline (2016-2019, January-December, weeks 1-52, and 2020, January-February, weeks 1-8), initial pandemic (2020, March-December, weeks 9-52, and 2021, January-June, weeks 1-26), and delta pandemic (2021, July-September, weeks 27-39) periods, using Alabama Department of Public Health database including deliveries with stillbirths ≥20 weeks or live births ≥22 weeks gestation. The primary outcomes were stillbirth and neonatal mortality rates. RESULTS: A total of 325,036 deliveries were included (236,481 from baseline, 74,076 from initial pandemic, and 14,479 from delta pandemic period). The neonatal mortality rate was lower in the pandemic periods (4.4 to 3.5 and 3.6/1000 live births, in the baseline, initial, and delta pandemic periods, respectively, p < 0.01), but the stillbirth rate did not differ (9 to 8.5 and 8.6/1000 births, p = 0.41). On interrupted time-series analyses, there were no significant changes in either stillbirth (p = 0.11 for baseline vs. initial pandemic period, and p = 0.67 for baseline vs. delta pandemic period) or neonatal mortality rates (p = 0.28 and 0.89, respectively). CONCLUSIONS: The COVID-19 pandemic periods were not associated with a significant change in stillbirth and neonatal mortality rates compared to the baseline period. IMPACT: The COVID-19 pandemic could have resulted in changes in fetal and neonatal outcomes. However, only a few population-based studies have compared the risk of fetal and neonatal mortality in the pandemic period to the baseline period. This population-based study identifies the changes in fetal and neonatal outcomes during the initial and delta COVID-19 pandemic period as compared to the baseline period. The current study shows that stillbirth and neonatal mortality rates were not significantly different in the initial and delta COVID-19 pandemic periods as compared to the baseline period.
Subject(s)
COVID-19 , Stillbirth , Infant, Newborn , Pregnancy , Female , Humans , Stillbirth/epidemiology , Pandemics , Alabama/epidemiology , Infant MortalityABSTRACT
BACKGROUND: During the COVID-19 pandemic within the United States, much of the responsibility for diagnostic testing and epidemiologic response has relied on the action of county-level departments of public health. Here we describe the integration of genomic surveillance into epidemiologic response within Humboldt County, a rural county in northwest California. METHODS: Through a collaborative effort, 853 whole SARS-CoV-2 genomes were generated, representing ~58% of the 1,449 SARS-CoV-2-positive cases detected in Humboldt County as of March 12, 2021. Phylogenetic analysis of these data was used to develop a comprehensive understanding of SARS-CoV-2 introductions to the county and to support contact tracing and epidemiologic investigations of all large outbreaks in the county. RESULTS: In the case of an outbreak on a commercial farm, viral genomic data were used to validate reported epidemiologic links and link additional cases within the community who did not report a farm exposure to the outbreak. During a separate outbreak within a skilled nursing facility, genomic surveillance data were used to rule out the putative index case, detect the emergence of an independent Spike:N501Y substitution, and verify that the outbreak had been brought under control. CONCLUSIONS: These use cases demonstrate how developing genomic surveillance capacity within local public health departments can support timely and responsive deployment of genomic epidemiology for surveillance and outbreak response based on local needs and priorities.
Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , Contact Tracing , Disease Outbreaks , Genomics , Humans , Pandemics , Phylogeny , Public Health Surveillance , SARS-CoV-2/geneticsABSTRACT
We reconstructed the 2016-2017 Zika virus epidemic in Puerto Rico by using complete genomes to uncover the epidemic's origin, spread, and evolutionary dynamics. Our study revealed that the epidemic was propelled by multiple introductions that spread across the island, intricate evolutionary patterns, and ≈10 months of cryptic transmission.
Subject(s)
Epidemics , Zika Virus Infection , Zika Virus , Evolution, Molecular , Humans , Puerto Rico/epidemiology , Zika Virus/genetics , Zika Virus Infection/epidemiologyABSTRACT
BACKGROUND: Colombia was the second most affected country during the American Zika virus (ZIKV) epidemic, with over 109,000 reported cases. Despite the scale of the outbreak, limited genomic sequence data were available from Colombia. We sought to sequence additional samples and use genomic epidemiology to describe ZIKV dynamics in Colombia. METHODS: We sequenced ZIKV genomes directly from clinical diagnostic specimens and infected Aedes aegypti samples selected to cover the temporal and geographic breadth of the Colombian outbreak. We performed phylogeographic analysis of these genomes, along with other publicly-available ZIKV genomes from the Americas, to estimate the frequency and timing of ZIKV introductions to Colombia. RESULTS: We attempted PCR amplification on 184 samples; 19 samples amplified sufficiently to perform sequencing. Of these, 8 samples yielded sequences with at least 50% coverage. Our phylogeographic reconstruction indicates two separate introductions of ZIKV to Colombia, one of which was previously unrecognized. We find that ZIKV was first introduced to Colombia in February 2015 (95%CI: Jan 2015 - Apr 2015), corresponding to 5 to 8 months of cryptic ZIKV transmission prior to confirmation in September 2015. Despite the presence of multiple introductions, we find that the majority of Colombian ZIKV diversity descends from a single introduction. We find evidence for movement of ZIKV from Colombia into bordering countries, including Peru, Ecuador, Panama, and Venezuela. CONCLUSIONS: Similarly to genomic epidemiological studies of ZIKV dynamics in other countries, we find that ZIKV circulated cryptically in Colombia. More accurately dating when ZIKV was circulating refines our definition of the population at risk. Additionally, our finding that the majority of ZIKV transmission within Colombia was attributable to transmission between individuals, rather than repeated travel-related importations, indicates that improved detection and control might have succeeded in limiting the scale of the outbreak within Colombia.
Subject(s)
Genome, Viral , Zika Virus Infection/virology , Zika Virus/genetics , Aedes/virology , Animals , Colombia/epidemiology , Disease Outbreaks , Evolution, Molecular , Genetic Variation , Humans , Phylogeny , Phylogeography , Zika Virus/classification , Zika Virus/isolation & purification , Zika Virus Infection/epidemiology , Zika Virus Infection/transmissionABSTRACT
Background: In 2014-2015, 242 individuals aged 2-89 years were newly diagnosed with human immunodeficiency virus type 1 (HIV-1) in Roka, a rural commune in Cambodia. A case-control study attributed the outbreak to unsafe injections. We aimed to reconstruct the likely transmission history of the outbreak. Methods: We assessed in 209 (86.4%) HIV-infected cases the presence of hepatitis C virus (HCV) and hepatitis B virus (HBV). We identified recent infections using antibody (Ab) avidity testing for HIV and HCV. We performed amplification, sequencing, and evolutionary phylogenetic analyses of viral strains. Geographical coordinates and parenteral exposure through medical services provided by an unlicensed healthcare practitioner were obtained from 193 cases and 1499 controls during interviews. Results: Cases were coinfected with HCV (78.5%) and HBV (12.9%). We identified 79 (37.8%) recent (<130 days) HIV infections. Phylogeny of 202 HIV env C2V3 sequences showed a 198-sample CRF01_AE strains cluster, with time to most recent common ancestor (tMRCA) in September 2013 (95% highest posterior density, August 2012-July 2014), and a peak of 15 infections/day in September 2014. Three geospatial HIV hotspots were discernible in Roka and correlated with high exposure to the practitioner (P = .04). Fifty-nine of 153 (38.6%) tested cases showed recent (<180 days) HCV infections. Ninety HCV NS5B sequences formed 3 main clades, 1 containing 34 subtypes 1b with tMRCA in 2012, and 2 with 51 subtypes 6e and tMRCAs in 2002-2003. Conclusions: Unsafe injections in Cambodia most likely led to an explosive iatrogenic spreading of HIV, associated with a long-standing and more genetically diverse HCV propagation.
Subject(s)
Disease Outbreaks , HIV Infections/epidemiology , HIV Infections/etiology , Injections/adverse effects , Adolescent , Adult , Aged , Aged, 80 and over , Cambodia/epidemiology , Case-Control Studies , Child , Child, Preschool , Female , HIV-1 , Humans , Iatrogenic Disease/epidemiology , Male , Middle Aged , Phylogeny , Rural Population , Young AdultSubject(s)
Myocarditis , Abatacept , Humans , Myocarditis/chemically induced , Myocarditis/drug therapy , Nivolumab , SteroidsABSTRACT
OBJECTIVE: Infants with "single ventricle" congenital heart disease are at high risk for sudden death following palliative surgical management. We developed a pilot telemedicine project to evaluate the feasibility of using Web-based daily reporting of clinical data with the goal of reducing unexpected admissions and sudden death. SUBJECTS AND METHODS: We enrolled 9 subjects (enrolled subjects [ES]) following surgical palliation over 12 months. Parents electronically transmitted ES daily weight and oxygen saturation and then completed an automated 10-point phone questionnaire on nutrition, activity, and distress. Subject enrollment continued until a second surgical palliative procedure (n=5), sudden death (n=2), or disenrollment (n=2). We collected clinical data on all ES and 9 historical controls (HC) from the preceding 18 months and analyzed clinical management, including outpatient telephone surveillance success, scheduled and unscheduled office and emergency department visits, hospitalizations, procedures, and adverse events, including death. RESULTS: Subject recruitment was more difficult than expected. Weight transmission success was high, but there was poor correlation between telemedicine system-measured oxygen saturation and a commercial monitor. The outpatient clinical telephone surveillance success rate for HC and ES was approximately 30%. After technical adjustments, parents of all ES (100%) were able to transmit questionnaire data. There were 9 emergency room visits for ES versus 11 unscheduled emergency room visits for HC. Sudden death occurred in 1 of 9 HC and 2 of 9 ES. CONCLUSIONS: Telemedicine monitoring for high-risk congenital heart disease patients is feasible but challenging, may reduce unscheduled visits, but may not impact the primary end point of preventing sudden death in this high-risk pediatric population.
Subject(s)
Cardiology/methods , Heart Defects, Congenital/surgery , Home Care Services, Hospital-Based/organization & administration , Internet , Pediatrics/methods , Telemedicine/methods , Body Weight , Death, Sudden, Cardiac , Emergency Service, Hospital/statistics & numerical data , Feasibility Studies , Female , Heart Defects, Congenital/mortality , Humans , Infant , Infant, Newborn , Male , Monitoring, Physiologic/methods , Oxygen/blood , Palliative Care , Pilot Projects , Surveys and QuestionnairesABSTRACT
Pathogen genomics can provide insights into disease transmission patterns, but new methods are needed to handle modern large-scale pathogen genome datasets. Genetically proximal viruses indicate epidemiological linkage and are informative about transmission events. Here, we leverage pairs of identical sequences using 114,298 SARS-CoV-2 genomes collected via sentinel surveillance from March 2021 to December 2022 in Washington State, USA, with linked age and residence information to characterize fine-scale transmission. The location of pairs of identical sequences is highly consistent with expectations from mobility and social contact data. Outliers in the relationship between genetic and mobility data can be explained by SARS-CoV-2 transmission between postal codes with male prisons, consistent with transmission between prison facilities. Transmission patterns between age groups vary across spatial scales. Finally, we use the timing of sequence collection to understand the age groups driving transmission. This work improves our ability to characterize transmission from large pathogen genome datasets.
ABSTRACT
Human neonates are at significantly greater risk of serious infection than immunocompetent adults. In particular, very low birth weight infants in the neonatal intensive care nursery are at high risk of developing life-threatening bacterial and fungal infections. Recent studies have identified Th17 cells as critical mediators of immunity to bacterial and fungal infections at epithelial barriers. Little is known, however, about the ontogeny of Th17-cell responses in humans. The frequency of serious bacterial infections in preterm infants and the importance of Th17 cells in providing protection against such infections in animal studies prompted us to study Th17-cell development in human neonates. Naïve CD4(+) T cells from extremely preterm infants, term infants, and adults were assayed for their capacity to develop into Th17 effector cells. Surprisingly, Th17-cell capacity was inversely related to developmental age. Neonates expressed higher levels of IL-23R, RORγt, and STAT3 prior to activation and showed a significant Th17-cell bias after activation. In contrast, adult cells expressed more TBX21 with a corresponding Th1-cell bias. CD161 expression on Th17-cell precursors was also developmentally regulated. Our results suggest there is significant developmental regulation of CD4(+) effector lineages with a strong bias toward Th17-cell development early in life.
Subject(s)
Cytokines/metabolism , Gene Expression Regulation, Developmental , Premature Birth/immunology , Th1 Cells/metabolism , Th17 Cells/metabolism , Adult , Antigens, CD/genetics , Antigens, CD/metabolism , Cell Separation , Cells, Cultured , Flow Cytometry , Gene Expression Regulation, Developmental/immunology , Humans , Infant, Newborn , Nuclear Receptor Subfamily 1, Group F, Member 3/genetics , Nuclear Receptor Subfamily 1, Group F, Member 3/metabolism , Receptors, Interleukin/genetics , Receptors, Interleukin/metabolism , STAT3 Transcription Factor/genetics , STAT3 Transcription Factor/metabolism , Signal Transduction/immunology , T-Box Domain Proteins/genetics , T-Box Domain Proteins/metabolism , Th1 Cells/immunology , Th1 Cells/pathology , Th1-Th2 Balance , Th17 Cells/immunology , Th17 Cells/pathologyABSTRACT
Seasonal influenza vaccines must be updated regularly to account for mutations that allow influenza viruses to escape our existing immunity. A successful vaccine should represent the genetic diversity of recently circulating viruses and induce antibodies that effectively prevent infection by those recent viruses. Thus, linking the genetic composition of circulating viruses and the serological experimental results measuring antibody efficacy is crucial to the vaccine design decision. Historically, genetic and serological data have been presented separately in the form of static visualizations of phylogenetic trees and tabular serological results to identify vaccine candidates. To simplify this decision-making process, we have created an interactive tool for visualizing serological data that has been integrated into Nextstrain's real-time phylogenetic visualization framework, Auspice. We show how the combined interactive visualizations may be used by decision makers to explore the relationships between complex data sets for both prospective vaccine virus selection and retrospectively exploring the performance of vaccine viruses.
ABSTRACT
Causes of non-malarial fevers in sub-Saharan Africa remain understudied. We hypothesized that metagenomic next-generation sequencing (mNGS), which allows for broad genomic-level detection of infectious agents in a biological sample, can systematically identify potential causes of non-malarial fevers. The 212 participants in this study were of all ages and were enrolled in a longitudinal malaria cohort in eastern Uganda. Between December 2020 and August 2021, respiratory swabs and plasma samples were collected at 313 study visits where participants presented with fever and were negative for malaria by microscopy. Samples were analyzed using CZ ID, a web-based platform for microbial detection in mNGS data. Overall, viral pathogens were detected at 123 of 313 visits (39%). SARS-CoV-2 was detected at 11 visits, from which full viral genomes were recovered from nine. Other prevalent viruses included Influenza A (14 visits), RSV (12 visits), and three of the four strains of seasonal coronaviruses (6 visits). Notably, 11 influenza cases occurred between May and July 2021, coinciding with when the Delta variant of SARS-CoV-2 was circulating in this population. The primary limitation of this study is that we were unable to estimate the contribution of bacterial microbes to non-malarial fevers, due to the difficulty of distinguishing bacterial microbes that were pathogenic from those that were commensal or contaminants. These results revealed the co-circulation of multiple viral pathogens likely associated with fever in the cohort during this time period. This study illustrates the utility of mNGS in elucidating the multiple potential causes of non-malarial febrile illness. A better understanding of the pathogen landscape in different settings and age groups could aid in informing diagnostics, case management, and public health surveillance systems.
ABSTRACT
Next-generation sequencing technology has revolutionised pathogen surveillance over the last two decades. However, the benefits are not equitably distributed, with developing countries lagging far behind in acquiring the required technology and analytical capacity. Recent declines in the cost associated with sequencing-equipment and running consumables have created an opportunity for broader adoption. During the COVID-19 pandemic, rapid diagnostics development and DNA sequencing revolutionised the ability to diagnose and sequence SARS-CoV-2 rapidly. Socioeconomic inequalities substantially impact the ability to sequence SARS-CoV-2 strains and undermine a developing country's pandemic preparedness. Low- and middle-income countries face additional challenges in establishing, maintaining and expanding genomic surveillance. We present our experience of establishing a genomic surveillance system at the Aga Khan University, Karachi, Pakistan. Despite being at a leading health sciences research institute in the country, we encountered significant challenges. These were related to collecting standardised contextual data for SARS-CoV-2 samples, procuring sequencing reagents and consumables, and challenges with library preparation, sequencing and submission of high-quality SARS-CoV-2 genomes. Several technical roadblocks ensued during the implementation of the genomic surveillance framework, which were resolved in collaboration with our partners. High-quality genome sequences were then deposited on open-access platforms per the best practices. Subsequently, these efforts culminated in deploying Pakistan's first SARS-CoV-2 phyllo surveillance map as a Nextstrain build. Our experience offers lessons for the successful development of Genomic Surveillance Infrastructure in resource-limited settings struck by a pandemic.
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , Pandemics , Genomics , Pakistan/epidemiologyABSTRACT
BACKGROUND: In the wake of the SARS-CoV-2 pandemic, scientists have scrambled to collect and analyze SARS-CoV-2 genomic data to inform public health responses to COVID-19 in real time. Open source phylogenetic and data visualization platforms for monitoring SARS-CoV-2 genomic epidemiology have rapidly gained popularity for their ability to illuminate spatial-temporal transmission patterns worldwide. However, the utility of such tools to inform public health decision-making for COVID-19 in real time remains to be explored. OBJECTIVE: The aim of this study is to convene experts in public health, infectious diseases, virology, and bioinformatics-many of whom were actively engaged in the COVID-19 response-to discuss and report on the application of phylodynamic tools to inform pandemic responses. METHODS: In total, 4 focus groups (FGs) occurred between June 2020 and June 2021, covering both the pre- and postvariant strain emergence and vaccination eras of the ongoing COVID-19 crisis. Participants included national and international academic and government researchers, clinicians, public health practitioners, and other stakeholders recruited through purposive and convenience sampling by the study team. Open-ended questions were developed to prompt discussion. FGs I and II concentrated on phylodynamics for the public health practitioner, while FGs III and IV discussed the methodological nuances of phylodynamic inference. Two FGs per topic area to increase data saturation. An iterative, thematic qualitative framework was used for data analysis. RESULTS: We invited 41 experts to the FGs, and 23 (56%) agreed to participate. Across all the FG sessions, 15 (65%) of the participants were female, 17 (74%) were White, and 5 (22%) were Black. Participants were described as molecular epidemiologists (MEs; n=9, 39%), clinician-researchers (n=3, 13%), infectious disease experts (IDs; n=4, 17%), and public health professionals at the local (PHs; n=4, 17%), state (n=2, 9%), and federal (n=1, 4%) levels. They represented multiple countries in Europe, the United States, and the Caribbean. Nine major themes arose from the discussions: (1) translational/implementation science, (2) precision public health, (3) fundamental unknowns, (4) proper scientific communication, (5) methods of epidemiological investigation, (6) sampling bias, (7) interoperability standards, (8) academic/public health partnerships, and (9) resources. Collectively, participants felt that successful uptake of phylodynamic tools to inform the public health response relies on the strength of academic and public health partnerships. They called for interoperability standards in sequence data sharing, urged careful reporting to prevent misinterpretations, imagined that public health responses could be tailored to specific variants, and cited resource issues that would need to be addressed by policy makers in future outbreaks. CONCLUSIONS: This study is the first to detail the viewpoints of public health practitioners and molecular epidemiology experts on the use of viral genomic data to inform the response to the COVID-19 pandemic. The data gathered during this study provide important information from experts to help streamline the functionality and use of phylodynamic tools for pandemic responses.
ABSTRACT
BACKGROUND: Food insecurity (FI) increases children's risk for illness and developmental and behavioral problems, which are ongoing concerns for congenital heart disease (CHD) patients. In 2020, 14.8% of households with children suffered from FI. The Hunger Vital Signs (HVS) asks 2 questions to assess FI. The global aim of the project is to implement HVS and connect FI families to resources. METHODS: Stakeholders identified 6 critical drivers in implementing FI screening at an outpatient cardiology clinic and conducted plan-do-study-act (PDSA) cycles to implement HVS. Over the 13-month study period, time series analyses were performed to assess our process measure (FI screening) and outcome measure (connection of FI families to resources). Demographics and severity of CHD were analyzed for FI families. RESULTS: Screening rates increased from 0% to >85%, screening 5064 families. Process evaluations revealed roadblocks including screening discomfort. FI families were more likely to identify as Black or multiple or other ethnicity. Severe CHD patients were at higher risk for FI (n = 106, odds ratio [OR] 1.67 [1.21-2.29], P = .002). Face-to-face meetings with social work and community partnerships reduced loss to follow-up and our ability to offer all FI families individualized FI resources. CONCLUSION: HVS screening can be implemented in a cardiology clinic to improve identification of FI families. A written tool can combat screening discomfort and improve identification of FI families. Children with severe CHD may be at increased risk for FI. A multidisciplinary team and community partnerships can improve individualized resource distribution.
Subject(s)
Cardiology , Food Supply , Ambulatory Care Facilities , Child , Food Insecurity , Humans , Mass ScreeningABSTRACT
The C29197T mutation is one of 4 point mutations known to cause N-gene target failure (NGTF) in the Xpert Xpress SARS-CoV-2 and Xpert Omni SARS-CoV-2 assays from Cepheid (Sunnyvale, CA). We describe a high local prevalence in January of 8.5% (CI 4.9-14.2%) for the C29197T mutation, which was over 3-fold higher than the prevalence estimated statewide in California during the same time frame, 2.5% (CI 2.1-2.8%). Using phylogenetic analysis, we discovered that this increase in prevalence was due, at least in part, to a disproportionately large infection cluster of unknown origin. This study emphasizes the importance of sequencing at the local jurisdictional level and demonstrates the impact that regional variation can have when assessing risk due to point mutations that impact clinical test performance. It also reinforces the need for diligent reporting of abnormal test results by clinical laboratories, especially during Emergency Use Authorization (EUA) periods, as additional information is gathered about the target organism and the performance of EUA-authorized tests over time.
Subject(s)
COVID-19 Testing/methods , COVID-19/diagnosis , SARS-CoV-2/isolation & purification , Genes, Viral , Humans , Molecular Diagnostic Techniques/methods , Mutation , Phylogeny , Prevalence , SARS-CoV-2/genetics , Sensitivity and SpecificityABSTRACT
BACKGROUND: The Public Health Alliance for Genomic Epidemiology (PHA4GE) (https://pha4ge.org) is a global coalition that is actively working to establish consensus standards, document and share best practices, improve the availability of critical bioinformatics tools and resources, and advocate for greater openness, interoperability, accessibility, and reproducibility in public health microbial bioinformatics. In the face of the current pandemic, PHA4GE has identified a need for a fit-for-purpose, open-source SARS-CoV-2 contextual data standard. RESULTS: As such, we have developed a SARS-CoV-2 contextual data specification package based on harmonizable, publicly available community standards. The specification can be implemented via a collection template, as well as an array of protocols and tools to support both the harmonization and submission of sequence data and contextual information to public biorepositories. CONCLUSIONS: Well-structured, rich contextual data add value, promote reuse, and enable aggregation and integration of disparate datasets. Adoption of the proposed standard and practices will better enable interoperability between datasets and systems, improve the consistency and utility of generated data, and ultimately facilitate novel insights and discoveries in SARS-CoV-2 and COVID-19. The package is now supported by the NCBI's BioSample database.