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PXVX0047 is an investigational vaccine developed for active immunization to prevent febrile acute respiratory disease (ARD) caused by adenovirus serotypes 4 (Ad4) and 7 (Ad7). PXVX0047 consists of a modernized, plasmid-derived vaccine that was generated using a virus isolated from Wyeth Ad4 and Ad7 vaccine tablets. A phase 1 two-arm, randomized, double-blind, active-controlled study was conducted to evaluate the safety profile and immunogenicity of the investigational adenovirus vaccines. The two components of PXVX0047 were administered orally together in a single dose to 11 subjects. For comparison, three additional subjects received the Ad4/Ad7 vaccine that is currently in use by the US military. The results of this study show that the tolerability and immunogenicity of the PXVX0047 Ad7 component are comparable with that of the control Ad4/Ad7 vaccine; however, the immunogenicity of the PXVX0047 Ad4 component was lower than expected. Clinical trial number NCT03160339.
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BACKGROUND: In 2020, preventive measures were implemented to mitigate the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among 600-700 recruits arriving weekly at a basic combat training (BCT) facility in the southern United States. Trainees were sorted into companies and platoons (cocoons) at arrival, tested, quarantined for 14 days with daily temperature and respiratory-symptom monitoring and retested before release into larger groups for training where symptomatic testing was conducted. Nonpharmaceutical measures, such as masking, and social distancing, were maintained throughout quarantine and BCT. We assessed for SARS-CoV-2 transmission in the quarantine milieu. METHODS: Nasopharyngeal (NP) swabs were collected at arrival and at the end of quarantine and blood specimens at both timepoints and at the end of BCT. Epidemiological characteristics were analyzed for transmission clusters identified from whole-genome sequencing of NP samples. RESULTS: Among 1403 trainees enrolled from 25 August to 7 October 2020, epidemiological analysis identified three transmission clusters (n = 20 SARS-CoV-2 genomes) during quarantine, which spanned five different cocoons. However, SARS-CoV-2 incidence decreased from 2.7% during quarantine to 1.5% at the end of BCT; prevalence at arrival was 3.3%. CONCLUSIONS: These findings suggest layered SARS-CoV-2 mitigation measures implemented during quarantine minimized the risk of further transmission in BCT.
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COVID-19 , Personal Militar , Humanos , Estados Unidos/epidemiología , SARS-CoV-2 , COVID-19/epidemiología , COVID-19/prevención & control , Cuarentena , Prueba de COVID-19RESUMEN
This report describes SARS-CoV-2 genomic surveillance conducted by the Department of Defense (DoD) Global Emerging Infections Surveillance Branch and the Next-Generation Sequencing and Bioinformatics Consortium (NGSBC) in response to the COVID-19 pandemic. Samples and sequence data were from SARS-CoV-2 infections occurring among Military Health System (MHS) beneficiaries from 1 March to 31 December 2020. There were 1,366 MHS samples sequenced from 10 countries, 36 U.S states or territories, and 5 Geographic Combatant Commands, representing approximately 2% of DoD cases in 2020. Genomes from these samples were compared with other public sequences; observed trends were similar to those of Centers for Disease Control and Prevention national surveillance in the U.S. with B.1, B.1.2, and other sub-lineages comprising the dominant variants of SARS-CoV-2. Sequence data were used to monitor transmission dynamics on U.S. Navy ships and at military training centers and installations. As new variants emerge, DoD medical and public health practitioners should maximize the use of genomic surveillance resources within DoD to inform force health protection measures.
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COVID-19 , Servicios de Salud Militares , Personal Militar , COVID-19/epidemiología , Genómica , Humanos , Pandemias , SARS-CoV-2/genéticaRESUMEN
Despite unprecedented global sequencing and surveillance of SARS-CoV-2, timely identification of the emergence and spread of novel variants of concern (VoCs) remains a challenge. Several million raw genome sequencing runs are now publicly available. We sought to survey these datasets for intrahost variation to study emerging mutations of concern. We developed iSKIM ("intrahost SARS-CoV-2 k-mer identification method") to relatively quickly and efficiently screen the many SARS-CoV-2 datasets to identify intrahost mutations belonging to lineages of concern. Certain mutations surged in frequency as intrahost minor variants just prior to, or while lineages of concern arose. The Spike N501Y change common to several VoCs was found as a minor variant in 834 samples as early as October 2020. This coincides with the timing of the first detected samples with this mutation in the Alpha/B.1.1.7 and Beta/B.1.351 lineages. Using iSKIM, we also found that Spike L452R was detected as an intrahost minor variant as early as September 2020, prior to the observed rise of the Epsilon/B.1.429/B.1.427 lineages in late 2020. iSKIM rapidly screens for mutations of interest in raw data, prior to genome assembly, and can be used to detect increases in intrahost variants, potentially providing an early indication of novel variant spread.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/diagnóstico , COVID-19/epidemiología , Mutación , Glicoproteína de la Espiga del Coronavirus/genéticaRESUMEN
BACKGROUND: With the emergence and spread of SARS-CoV-2 variants, genomic epidemiology and surveillance have proven invaluable tools for variant tracking. Here, we analyzed SARS-CoV-2 samples collected from personnel located at the US/NATO bases across Afghanistan. RESULTS: Sequencing and phylogenetic analyses revealed at least 16 independent introductions of SARS-CoV-2 into four of these relatively isolated compounds during April and May 2021, including multiple introductions of Alpha and Delta variants. Four of the introductions resulted in sustained spread of the virus within, and in two cases between, the compounds. Three of these outbreaks, one Delta and two Alpha, occurred simultaneously. CONCLUSIONS: Even in rigorously controlled and segregated environments, SARS-CoV-2 introduction and spread may occur frequently.
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COVID-19 , Personal Militar , Afganistán/epidemiología , COVID-19/epidemiología , Brotes de Enfermedades , Genómica , Humanos , Filogenia , SARS-CoV-2/genéticaRESUMEN
Neutralizing antibodies are important correlates of protection against dengue. Yet, determinants of variation in neutralization across strains within the four dengue virus serotypes (DENV1-4) is imperfectly understood. Studies focus on structural DENV proteins, especially the envelope (E), the primary target of anti-DENV antibodies. Although changes in immune recognition (antigenicity) are often attributed to variation in epitope residues, viral processes influencing conformation and epitope accessibility also affect neutralizability, suggesting possible modulating roles of nonstructural proteins. We estimated effects of residue changes in all 10 DENV proteins on antigenic distances between 348 DENV collected from individuals living in Bangkok, Thailand (1994-2014). Antigenic distances were derived from response of each virus to a panel of twenty non-human primate antisera. Across 100 estimations, excluding 10% of virus pairs each time, 77 of 295 positions with residue variability in E consistently conferred antigenic effects; 52 were within ±3 sites of known binding sites of neutralizing human monoclonal antibodies, exceeding expectations from random assignments of effects to sites (p = 0.037). Effects were also identified for 16 sites on the stem/anchor of E which were only recently shown to become exposed under physiological conditions. For all proteins, except nonstructural protein 2A (NS2A), root-mean-squared-error (RMSE) in predicting distances between pairs held out in each estimation did not outperform sequences of equal length derived from all proteins or E, suggesting that antigenic signals present were likely through linkage with E. Adjusted for E, we identified 62/219 sites embedding the excess signals in NS2A. Concatenating these sites to E additionally explained 3.4% to 4.0% of observed variance in antigenic distances compared to E alone (50.5% to 50.8%); RMSE outperformed concatenating E with sites from any protein of the virus (ΔRMSE, 95%IQR: 0.01, 0.05). Our results support examining antigenic determinants beyond the DENV surface.
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Virus del Dengue , Dengue , Aminoácidos , Animales , Anticuerpos Monoclonales , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Epítopos/genética , Tailandia , Proteínas del Envoltorio ViralRESUMEN
On 28 May 2021, leisure travel restrictions in place to control coronavirus disease 2019 (COVID-19) were eased among vaccinated U.S. military personnel and beneficiaries stationed in South Korea (USFK) allowing access to bars and clubs which were off limits. We describe results from an investigation of the largest severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak as of November 2021 among USFK personnel following this change in policy. Data such as SARS-CoV-2 real-time polymerase chain reaction (RT-PCR) test results, demographic characteristics, symptom and vaccination histories, and genome sequences were analyzed. Of a total 207 new cases of COVID-19 diagnosed among USFK members from 15 June to 27 July 2021, 113 (57%) eligible cases were fully vaccinated, of whom 86 (76%) were symptomatic. RT-PCR cycling threshold values were similar among vaccinated and unvaccinated members. Whole genomic sequencing of 54 outbreak samples indicated all infections were due to the Delta variant. Phylogenetic analysis revealed two sources of SARS-CoV-2 accounted for 41% of infections among vaccinated and unvaccinated members. Vaccinated personnel were not at risk of severe illness; however, 86% experienced symptoms following infection. There were no hospitalizations among COVID-19 cases, most of whom were young military service members. Rescinded restrictions were reinstated to control the outbreak. Masking was mandated among all personnel predating U.S. national recommendations for indoor masking in high COVID-19 transmission areas. Increased vaccination with continued vigilance and extension of COVID-19 mitigation measures are warranted to contain the spread of SARS-CoV-2 variants of concern.
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Infection with one of dengue viruses 1 to 4 (DENV1-4) induces protective antibodies against homotypic infection. However, a notable feature of dengue viruses is the ability to use preexisting heterotypic antibodies to infect Fcγ receptorbearing immune cells, leading to higher viral load and immunopathological events that augment disease. We tracked the antigenic dynamics of each DENV serotype by using 1944 sequenced isolates from Bangkok, Thailand, between 1994 and 2014 (348 strains), in comparison with regional and global DENV antigenic diversity (64 strains). Over the course of 20 years, the Thailand DENV serotypes gradually evolved away from one another. However, for brief periods, the serotypes increased in similarity, with corresponding changes in epidemic magnitude. Antigenic evolution within a genotype involved a trade-off between two types of antigenic change (within-serotype and between-serotype), whereas genotype replacement resulted in antigenic change away from all serotypes. These findings provide insights into theorized dynamics in antigenic evolution.
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Variación Antigénica , Antígenos Virales/inmunología , Virus del Dengue/inmunología , Dengue/virología , Evolución Molecular , Anticuerpos Antivirales/inmunología , Acrecentamiento Dependiente de Anticuerpo , Antígenos Virales/genética , Dengue/epidemiología , Dengue/inmunología , Virus del Dengue/genética , Humanos , Evasión Inmune , Serogrupo , Tailandia/epidemiología , Factores de TiempoRESUMEN
The SARS-CoV-2 pandemic prompts evaluation of recombination in human coronavirus (hCoV) evolution. We undertook recombination analyses of 158,118 public seasonal hCoV, SARS-CoV-1, SARS-CoV-2 and MERS-CoV genome sequences using the RDP4 software. We found moderate evidence for 8 SARS-CoV-2 recombination events, two of which involved the spike gene, and low evidence for one SARS-CoV-1 recombination event. Within MERS-CoV, 229E, OC43, NL63 and HKU1 datasets, we noted 7, 1, 9, 14, and 1 high-confidence recombination events, respectively. There was propensity for recombination breakpoints in the non-ORF1 region of the genome containing structural genes, and recombination severely skewed the temporal structure of these data, especially for NL63 and OC43. Bayesian time-scaled analyses on recombinant-free data indicated the sampled diversity of seasonal CoVs emerged in the last 70 years, with 229E displaying continuous lineage replacements. These findings emphasize the importance of genomic based surveillance to detect recombination in SARS-CoV-2, particularly if recombination may lead to immune evasion.
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Coronavirus del Síndrome Respiratorio de Oriente Medio/genética , Recombinación Genética , SARS-CoV-2/genética , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/genética , Teorema de Bayes , Bases de Datos Genéticas , Genoma Viral , Humanos , Evasión Inmune , Coronavirus del Síndrome Respiratorio de Oriente Medio/clasificación , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/clasificación , SARS-CoV-2/clasificación , Glicoproteína de la Espiga del Coronavirus/genética , Proteínas no Estructurales Virales/genéticaRESUMEN
The long-lasting global COVID-19 pandemic demands timely genomic investigation of SARS-CoV-2 viruses. Here, we report a simple and efficient workflow for whole-genome sequencing utilizing one-step reverse transcription-PCR (RT-PCR) amplification on a microfluidic platform, followed by MiSeq amplicon sequencing. The method uses Fluidigm integrated fluidic circuit (IFC) and instruments to amplify 48 samples with 39 pairs of primers, including 35 custom-designed primer pairs and four additional primer pairs from the ARTIC network protocol v3. Application of this method on RNA samples from both viral isolates and clinical specimens demonstrates robustness and efficiency in obtaining the full genome sequence of SARS-CoV-2.
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Genoma Viral , Secuenciación de Nucleótidos de Alto Rendimiento , Microfluídica , SARS-CoV-2/genética , Secuenciación Completa del Genoma , COVID-19/virología , Cartilla de ADN , Humanos , ARN Viral/genética , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Intra-host single nucleotide variants (iSNVs) have been increasingly used in genomic epidemiology to increase phylogenetic resolution and reconstruct fine-scale outbreak dynamics. These analyses are preferably done on sequence data from direct clinical samples, but in many cases due to low viral loads, there might not be enough genetic material for deep sequencing and iSNV determination. Isolation of the virus from clinical samples with low-passage number increases viral load, but few studies have investigated how dengue virus (DENV) culture isolation from a clinical sample impacts the consensus sequence and the intra-host virus population frequencies. In this study, we investigate consensus and iSNV frequency differences between DENV sequenced directly from clinical samples and their corresponding low-passage isolates. Twenty five DENV1 and DENV2 positive sera and their corresponding viral isolates (T. splendens inoculation and C6/36 passage) were obtained from a prospective cohort study in the Philippines. These were sequenced on MiSeq with minimum nucleotide depth of coverage of 500×, and iSNVs were detected using LoFreq. For both DENV1 and DENV2, we found a maximum of one consensus nucleotide difference between clinical sample and isolate. Interestingly, we found that iSNVs with frequencies ≥5â% were often preserved between the samples, and that the number of iSNV positions, and sample diversity, at this frequency cutoff did not differ significantly between the sample pairs (clinical sample and isolate) in either DENV1 or DENV2 data. Our results show that low-passage DENV isolate consensus genomes are largely representative of their direct sample parental viruses, and that low-passage isolates often mirror high frequency within-host variants from direct samples.
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Virus del Dengue/clasificación , Virus del Dengue/genética , Dengue/virología , Variación Genética , Secuencia de Bases , Virus del Dengue/aislamiento & purificación , Genoma Viral , Humanos , Filipinas , Filogenia , Estudios Prospectivos , ARN Viral/genéticaRESUMEN
Here, we report two complete genome sequences of human adenovirus 55 (HAdV-55) isolates, from a patient in Pennsylvania in 2006 and a U.S. military member in South Korea in 2019. The findings demonstrate the continued global transmission of HAdV-55 viruses in both military and civilian populations.
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The COVID-19 pandemic has sparked an urgent need to uncover the underlying biology of this devastating disease. Though RNA viruses mutate more rapidly than DNA viruses, there are a relatively small number of single nucleotide polymorphisms (SNPs) that differentiate the main SARS-CoV-2 lineages that have spread throughout the world. In this study, we investigated 129 RNA-seq data sets and 6928 consensus genomes to contrast the intra-host and inter-host diversity of SARS-CoV-2. Our analyses yielded three major observations. First, the mutational profile of SARS-CoV-2 highlights intra-host single nucleotide variant (iSNV) and SNP similarity, albeit with differences in C > U changes. Second, iSNV and SNP patterns in SARS-CoV-2 are more similar to MERS-CoV than SARS-CoV-1. Third, a significant fraction of insertions and deletions contribute to the genetic diversity of SARS-CoV-2. Altogether, our findings provide insight into SARS-CoV-2 genomic diversity, inform the design of detection tests, and highlight the potential of iSNVs for tracking the transmission of SARS-CoV-2.
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COVID-19/diagnóstico , COVID-19/transmisión , Variación Genética , Genoma Viral , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , SARS-CoV-2/genética , COVID-19/virología , Interacciones Huésped-Patógeno , Humanos , Polimorfismo de Nucleótido SimpleRESUMEN
INTRODUCTION: High quality epidemic forecasting and prediction are critical to support response to local, regional and global infectious disease threats. Other fields of biomedical research use consensus reporting guidelines to ensure standardization and quality of research practice among researchers, and to provide a framework for end-users to interpret the validity of study results. The purpose of this study was to determine whether guidelines exist specifically for epidemic forecast and prediction publications. METHODS: We undertook a formal systematic review to identify and evaluate any published infectious disease epidemic forecasting and prediction reporting guidelines. This review leveraged a team of 18 investigators from US Government and academic sectors. RESULTS: A literature database search through May 26, 2019, identified 1467 publications (MEDLINE nâ¯=â¯584, EMBASE nâ¯=â¯883), and a grey-literature review identified a further 407 publications, yielding a total 1777 unique publications. A paired-reviewer system screened in 25 potentially eligible publications, of which two were ultimately deemed eligible. A qualitative review of these two published reporting guidelines indicated that neither were specific for epidemic forecasting and prediction, although they described reporting items which may be relevant to epidemic forecasting and prediction studies. CONCLUSIONS: This systematic review confirms that no specific guidelines have been published to standardize the reporting of epidemic forecasting and prediction studies. These findings underscore the need to develop such reporting guidelines in order to improve the transparency, quality and implementation of epidemic forecasting and prediction research in operational public health.
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Notificación de Enfermedades/métodos , Epidemias , Enfermedades Transmisibles , Notificación de Enfermedades/estadística & datos numéricos , Predicción , Guías como Asunto , Humanos , Salud PúblicaRESUMEN
Epidemics of emerging and re-emerging infectious diseases are a danger to civilian and military populations worldwide. Health security and mitigation of infectious disease threats is a priority of the United States Government and the Department of Defense (DoD). Next generation sequencing (NGS) and Bioinformatics (BI) enhances traditional biosurveillance by providing additional data to understand transmission, identify resistance and virulence factors, make predictions, and update risk assessments. As more and more laboratories adopt NGS and BI technologies they encounter challenges in building local capacity. In addition to choosing the right sequencing platform and approach, considerations must also be made for the complexity of bioinformatics analyses, data storage, as well as personnel and computational requirements. To address these needs, a comprehensive training program was developed covering wet lab and bioinformatics approaches to NGS. The program is meant to be modular and adaptive to meet both common and individualized needs of medical research and public health laboratories across the DoD. The training program was first deployed internationally to the Basic Science Laboratory of the US Army Medical Research Directorate-Africa in Kisumu, Kenya, which is an overseas Lab of the Walter Reed Army Institute of Research (WRAIR). A week-long workshop with intensive focus on targeted sequencing and the bioinformatics of genome assembly (n = 24 participants) was held. Post-workshop self-assessment (completed by 21 participants) noted significant median gains in knowledge domains related to NGS targeted sequencing, bioinformatics for genome assembly, and sequence quality assessment. The participants also reported that the information on study design, sample preparation, sequencing quality control, data quality assessment, reporting, and basic and advanced bioinformatics analysis were the most useful information presented in the training. While longer-term evaluations are planned, the training resulted in significant short-term improvement of a laboratory's self-reported wet lab and bioinformatics capabilities. This framework can be used for future DoD laboratory development in the area of NGS and BI for infectious disease surveillance, ultimately enhancing this global DoD capability.
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Dengue is one of the most widespread vector-borne viral diseases in the world. However, the size, heterogeneity, and temporal dynamics of the cell-associated viral reservoir during acute dengue virus (DENV) infection remains unclear. In this study, we analyzed cells infected in vitro with DENV and PBMC from an individual experiencing a natural DENV infection utilizing 5' capture single cell RNA sequencing (scRNAseq). Both positive- and negative-sense DENV RNA was detected in reactions containing either an oligo(dT) primer alone, or in reactions supplemented with a DENV-specific primer. The addition of a DENV-specific primer did not increase the total amount of DENV RNA captured or the fraction of cells identified as containing DENV RNA. However, inclusion of a DENV-specific cDNA primer did increase the viral genome coverage immediately 5' to the primer binding site. Furthermore, while the majority of intracellular DENV sequence captured in this analysis mapped to the 5' end of the viral genome, distinct patterns of enhanced coverage within the DENV polyprotein coding region were observed. The 5' capture scRNAseq analysis of PBMC not only recapitulated previously published reports by detecting virally infected memory and naïve B cells, but also identified cell-associated genomic variants not observed in contemporaneous serum samples. These results demonstrate that oligo(dT) primed 5' capture scRNAseq can detect DENV RNA and quantify virus-infected cells in physiologically relevant conditions, and provides insight into viral sequence variability within infected cells.
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Dengue/genética , Análisis de Secuencia de ARN/métodos , Linfocitos B/metabolismo , Cartilla de ADN/genética , ADN Complementario/genética , Virus del Dengue/genética , Virus del Dengue/patogenicidad , Virus del Dengue/fisiología , Genoma Viral/genética , Humanos , Leucocitos Mononucleares/metabolismo , Oligodesoxirribonucleótidos/genética , ARN Viral/genéticaRESUMEN
BACKGROUND: In recent years, Ecuador and other South American countries have experienced an increase in arboviral diseases. A rise in dengue infections was followed by introductions of chikungunya and Zika, two viruses never before seen in many of these areas. Furthermore, the latest socioeconomic and political instability in Venezuela and the mass migration of its population into the neighboring countries has given rise to concerns of infectious disease spillover and escalation of arboviral spread in the region. RESULTS: We performed phylogeographic analyses of dengue (DENV) and chikungunya (CHIKV) virus genomes sampled from a surveillance site in Ecuador in 2014-2015, along with genomes from the surrounding countries. Our results revealed at least two introductions of DENV, in 2011 and late 2013, that initially originated from Venezuela and/or Colombia. The introductions were subsequent to increases in the influx of Venezuelan and Colombian citizens into Ecuador, which in 2013 were 343% and 214% higher than in 2009, respectively. However, we show that Venezuela has historically been an important source of DENV dispersal in this region, even before the massive exodus of its population, suggesting already established paths of viral distribution. Like DENV, CHIKV was introduced into Ecuador at multiple time points in 2013-2014, but unlike DENV, these introductions were associated with the Caribbean. Our findings indicated no direct CHIKV connection between Ecuador, Colombia, and Venezuela as of 2015, suggesting that CHIKV was, at this point, not following the paths of DENV spread. CONCLUSION: Our results reveal that Ecuador is vulnerable to arbovirus import from many geographic locations, emphasizing the need of continued surveillance and more diversified prevention strategies. Importantly, increase in human movement along established paths of viral dissemination, combined with regional outbreaks and epidemics, may facilitate viral spread and lead to novel virus introductions. Thus, strengthening infectious disease surveillance and control along migration routes and improving access to healthcare for the vulnerable populations is of utmost importance.
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Fiebre Chikungunya/epidemiología , Virus Chikungunya/clasificación , Virus Chikungunya/genética , Virus del Dengue/clasificación , Virus del Dengue/genética , Dengue/epidemiología , Emigración e Inmigración/estadística & datos numéricos , Fiebre Chikungunya/transmisión , Fiebre Chikungunya/virología , Virus Chikungunya/aislamiento & purificación , Colombia/epidemiología , Dengue/transmisión , Dengue/virología , Virus del Dengue/aislamiento & purificación , Brotes de Enfermedades , Ecuador/epidemiología , Emigración e Inmigración/tendencias , Genoma Viral , Genotipo , Humanos , Mutación Missense/fisiología , Fenotipo , Filogeografía , Análisis de Secuencia de ADN , América del Sur/epidemiología , Venezuela/epidemiología , Virus Zika/aislamiento & purificación , Infección por el Virus Zika/epidemiología , Infección por el Virus Zika/transmisión , Infección por el Virus Zika/virologíaRESUMEN
Next-generation sequencing technologies, exponential increases in the availability of virus genomic data, and ongoing advances in phylogenomic methods have made genomic epidemiology an increasingly powerful tool for public health response to a range of mosquito-borne virus outbreaks. In this review, we offer a brief primer on the scope and methods of phylogenomic analyses that can answer key epidemiological questions during mosquito-borne virus public health emergencies. We then focus on case examples of outbreaks, including those caused by dengue, Zika, yellow fever, West Nile, and chikungunya viruses, to demonstrate the utility of genomic epidemiology to support the prevention and control of mosquito-borne virus threats. We extend these case studies with operational perspectives on how to best incorporate genomic epidemiology into structured surveillance and response programs for mosquito-borne virus control. Many tools for genomic epidemiology already exist, but so do technical and nontechnical challenges to advancing their use. Frameworks to support the rapid sharing of multidimensional data and increased cross-sector partnerships, networks, and collaborations can support advancement on all scales, from research and development to implementation by public health agencies.
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Culicidae/virología , Brotes de Enfermedades/prevención & control , Genómica , Control de Mosquitos , Salud Pública , Enfermedades Transmitidas por Vectores/prevención & control , Animales , Fiebre Chikungunya/epidemiología , Fiebre Chikungunya/prevención & control , Fiebre Chikungunya/virología , Virus Chikungunya/genética , Dengue/epidemiología , Dengue/prevención & control , Dengue/virología , Humanos , Mosquitos Vectores/virología , Enfermedades Transmitidas por Vectores/epidemiología , Enfermedades Transmitidas por Vectores/virología , Fiebre del Nilo Occidental/epidemiología , Fiebre del Nilo Occidental/prevención & control , Fiebre del Nilo Occidental/virología , Fiebre Amarilla/epidemiología , Fiebre Amarilla/prevención & control , Fiebre Amarilla/virología , Virus Zika/genética , Infección por el Virus Zika/epidemiología , Infección por el Virus Zika/prevención & control , Infección por el Virus Zika/virologíaRESUMEN
Next generation sequencing (NGS) combined with bioinformatics has successfully been used in a vast array of analyses for infectious disease research of public health relevance. For instance, NGS and bioinformatics approaches have been used to identify outbreak origins, track transmissions, investigate epidemic dynamics, determine etiological agents of a disease, and discover novel human pathogens. However, implementation of high-quality NGS and bioinformatics in research and public health laboratories can be challenging. These challenges mainly include the choice of the sequencing platform and the sequencing approach, the choice of bioinformatics methodologies, access to the appropriate computation and information technology infrastructure, and recruiting and retaining personnel with the specialized skills and experience in this field. In this review, we summarize the most common NGS and bioinformatics workflows in the context of infectious disease genomic surveillance and pathogen discovery, and highlight the main challenges and considerations for setting up an NGS and bioinformatics-focused infectious disease research public health laboratory. We describe the most commonly used sequencing platforms and review their strengths and weaknesses. We review sequencing approaches that have been used for various pathogens and study questions, as well as the most common difficulties associated with these approaches that should be considered when implementing in a public health or research setting. In addition, we provide a review of some common bioinformatics tools and procedures used for pathogen discovery and genome assembly, along with the most common challenges and solutions. Finally, we summarize the bioinformatics of advanced viral, bacterial, and parasite pathogen characterization, including types of study questions that can be answered when utilizing NGS and bioinformatics.