Last data update: Nov 11, 2024. (Total: 48109 publications since 2009)
Records 1-30 (of 165 Records) |
Query Trace: Trees E[original query] |
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Fatal injuries among landscaping and tree care workers: Insights from NIOSH and state-based FACE reports
Kearney GD , Romano N , Doub A . J Saf Res 2024 91 393-400 Context: A comprehensive assessment of the National Institute for Occupational Safety and Health (NIOSH) and State-based Fatal Assessment and Control Evaluation (FACE) investigative reports involving landscaping and tree worker fatalities have not been fully examined. Methods: Narrative text from 93 FACE reports from 1987 to 2023 involving landscaping and tree care workers were reviewed, manually coded and analyzed on major variables. Univariate analyses was conducted to summarize results of decedent workers and workplace characteristics. Results: Among the total number of worker fatalities (n = 95), the most commonly reported incidents were, electrocutions from power lines (18.3%), falls from trees (16.1%), and incidents involving a worker being either caught, pulled, or dragged into wood-chipping machine (12.9%). More than 66.0% of fatal incidents occurred among tree care workers that had been on the job for one year or less. Among reports, 60.2% of employers lacked a written safety plan, and 34.4% did not provide job training to their workers. Conclusions: FACE case reports alone are not a valid measure of workplace fatalities. Nevertheless, the codification and descriptive summary of more than three decades of case reports increases understanding of circumstances and contributing risk factors associated with these tragic, and yet largely preventable incidents. A comprehensive approach is urgently needed that includes: (a) taking immediate action to reduce occupational risks while cultivating a robust safety culture across the industry, and (b) increasing research to evaluate the effectiveness of interventions and prevention measures. Practical Application: The interconnectedness of safety challenges requires a multi-faceted approach that includes addressing issues related to new and diverse workers, employer commitments to the implementation of safety plans, and comprehensive training and mentorship programs. Intervention strategies and implementation measures are essential to diminishing fatalities in these high-risk jobs. © 2024 National Safety Council and Elsevier Ltd |
Genetic diversity in Salmonella enterica in outbreaks of foodborne and zoonotic origin in the USA in 2006-2017
Trees E , Carleton HA , Folster JP , Gieraltowski L , Hise K , Leeper M , Nguyen TA , Poates A , Sabol A , Tagg KA , Tolar B , Vasser M , Webb HE , Wise M , Lindsey RL . Microorganisms 2024 12 (8) Whole genome sequencing is replacing traditional laboratory surveillance methods as the primary tool to track and characterize clusters and outbreaks of the foodborne and zoonotic pathogen Salmonella enterica (S. enterica). In this study, 438 S. enterica isolates representing 35 serovars and 13 broad vehicle categories from one hundred epidemiologically confirmed outbreaks were evaluated for genetic variation to develop epidemiologically relevant interpretation guidelines for Salmonella disease cluster detection. The Illumina sequences were analyzed by core genome multi-locus sequence typing (cgMLST) and screened for antimicrobial resistance (AR) determinants and plasmids. Ninety-three of the one hundred outbreaks exhibited a close allele range (less than 10 allele differences with a subset closer than 5). The remaining seven outbreaks showed increased variation, of which three were considered polyclonal. A total of 16 and 28 outbreaks, respectively, showed variations in the AR and plasmid profiles. The serovars Newport and I 4,[5],12:i:-, as well as the zoonotic and poultry product vehicles, were overrepresented among the outbreaks, showing increased variation. A close allele range in cgMLST profiles can be considered a reliable proxy for epidemiological relatedness for the vast majority of S. enterica outbreak investigations. Variations associated with mobile elements happen relatively frequently during outbreaks and could be reflective of changing selective pressures. |
Evaluation of the increased genetic resolution and utility for source tracking of a recently developed method for genotyping cyclospora cayetanensis
Leonard SR , Mammel MK , Almeria S , Gebru ST , Jacobson DK , Peterson AC , Barratt JLN , Musser SM . Microorganisms 2024 12 (5) Cyclospora cayetanensis is a foodborne parasite that causes cyclosporiasis, an enteric illness in humans. Genotyping methods are used to genetically discriminate between specimens from cyclosporiasis cases and can complement source attribution investigations if the method is sufficiently sensitive for application to food items. A very sensitive targeted amplicon sequencing (TAS) assay for genotyping C. cayetanensis encompassing 52 loci was recently designed. In this study, we analyzed 66 genetically diverse clinical specimens to assess the change in phylogenetic resolution between the TAS assay and a currently employed eight-marker scheme. Of the 52 markers, ≥50 were successfully haplotyped for all specimens, and these results were used to generate a hierarchical cluster dendrogram. Using a previously described statistical approach to dissect hierarchical trees, the 66 specimens resolved into 24 and 27 distinct genetic clusters for the TAS and an 8-loci scheme, respectively. Although the specimen composition of 15 clusters was identical, there were substantial differences between the two dendrograms, highlighting the importance of both inclusion of additional genome coverage and choice of loci to target for genotyping. To evaluate the ability to genetically link contaminated food samples with clinical specimens, C. cayetanensis was genotyped from DNA extracted from raspberries inoculated with fecal specimens. The contaminated raspberry samples were assigned to clusters with the corresponding clinical specimen, demonstrating the utility of the TAS assay for traceback efforts. |
Understanding forms of childhood adversities and associations with adult health outcomes: A regression tree analysis
Perrins SP , Vermes E , Cincotta K , Xu Y , Godoy-Garraza L , Chen MS , Addison R , Douglas B , Yatco A , Idaikkadar N , Willis LA . Child Abuse Negl 2024 153 106844 BACKGROUND: Empirical studies have demonstrated associations between ten original adverse childhood experiences (ACEs) and multiple health outcomes. Identifying expanded ACEs can capture the burden of other childhood adversities that may have important health implications. OBJECTIVE: We sought to identify childhood adversities that warrant consideration as expanded ACEs. We hypothesized that experiencing expanded and original ACEs would be associated with poorer adult health outcomes compared to experiencing original ACEs alone. PARTICIPANTS: The 11,545 respondents of the National Longitudinal Surveys (NLS) and Child and Young Adult Survey were 48.9 % female, 22.7 % Black, 15.8 % Hispanic, 36.1 % White, 1.7 % Asian/Native Hawaiian/Pacific Islander/Native American/Native Alaskan, and 7.5 % Other. METHODS: This study used regression trees and generalized linear models to identify if/which expanded ACEs interacted with original ACEs in association with six health outcomes. RESULTS: Four expanded ACEs-basic needs instability, lack of parental love and affection, community stressors, and mother's experience with physical abuse during childhood -significantly interacted with general health, depressive symptom severity, anxiety symptom severity, and violent crime victimization in adulthood (all p-values <0.005). Basic needs instability and/or lack of parental love and affection emerged as correlates across multiple outcomes. Experiencing lack of parental love and affection and original ACEs was associated with greater anxiety symptoms (p = 0.022). CONCLUSIONS: This is the first study to use supervised machine learning to investigate interaction effects among original ACEs and expanded ACEs. Two expanded ACEs emerged as predictors for three adult health outcomes and warrant further consideration in ACEs assessments. |
Genomic sequencing of Neisseria gonorrhoeae to respond to the urgent threat of antimicrobial-resistant gonorrhea.
Abrams AJ , Trees DL . Pathog Dis 2017 75 (4) The development of resistance of Neisseria gonorrhoeae to available first-line antibiotics, including penicillins, tetracyclines, fluoroquinolones and cephalosporins, has led to the circulation of multidrug-resistant gonorrhea at a global scale. Advancements in high-throughput whole-genome sequencing (WGS) provide useful tools that can be used to enhance gonococcal detection, treatment and management capabilities, which will ultimately aid in the control of antimicrobial resistant gonorrhea worldwide. In this minireview, we discuss the application of WGS of N. gonorrhoeae to strain typing, phylogenomic, molecular surveillance and transmission studies. We also examine the application of WGS analyses to the public health sector as well as the potential usage of WGS-based transcriptomic and epigenetic methods to identify novel gonococcal resistance mechanisms. |
2020 Ebola virus disease outbreak in Équateur Province, Democratic Republic of the Congo: a retrospective genomic characterisation
Kinganda-Lusamaki E , Whitmer S , Lokilo-Lofiko E , Amuri-Aziza A , Muyembe-Mawete F , Makangara-Cigolo JC , Makaya G , Mbuyi F , Whitesell A , Kallay R , Choi M , Pratt C , Mukadi-Bamuleka D , Kavunga-Membo H , Matondo-Kuamfumu M , Mambu-Mbika F , Ekila-Ifinji R , Shoemaker T , Stewart M , Eng J , Rajan A , Soke GN , Fonjungo PN , Otshudiema JO , Folefack GLT , Pukuta-Simbu E , Talundzic E , Shedroff E , Bokete JL , Legand A , Formenty P , Mores CN , Porzucek AJ , Tritsch SR , Kombe J , Tshapenda G , Mulangu F , Ayouba A , Delaporte E , Peeters M , Wiley MR , Montgomery JM , Klena JD , Muyembe-Tamfum JJ , Ahuka-Mundeke S , Mbala-Kingebeni P . Lancet Microbe 2024 BACKGROUND: The Democratic Republic of the Congo has had 15 Ebola virus disease (EVD) outbreaks, from 1976 to 2023. On June 1, 2020, the Democratic Republic of the Congo declared an outbreak of EVD in the western Équateur Province (11th outbreak), proximal to the 2018 Tumba and Bikoro outbreak and concurrent with an outbreak in the eastern Nord Kivu Province. In this Article, we assessed whether the 11th outbreak was genetically related to previous or concurrent EVD outbreaks and connected available epidemiological and genetic data to identify sources of possible zoonotic spillover, uncover additional unreported cases of nosocomial transmission, and provide a deeper investigation into the 11th outbreak. METHODS: We analysed epidemiological factors from the 11th EVD outbreak to identify patient characteristics, epidemiological links, and transmission modes to explore virus spread through space, time, and age groups in the Équateur Province, Democratic Republic of the Congo. Trained field investigators and health professionals recorded data on suspected, probable, and confirmed cases, including demographic characteristics, possible exposures, symptom onset and signs and symptoms, and potentially exposed contacts. We used blood samples from individuals who were live suspected cases and oral swabs from individuals who were deceased to diagnose EVD. We applied whole-genome sequencing of 87 available Ebola virus genomes (from 130 individuals with EVD between May 19 and Sept 16, 2020), phylogenetic divergence versus time, and Bayesian reconstruction of phylogenetic trees to calculate viral substitution rates and study viral evolution. We linked the available epidemiological and genetic datasets to conduct a genomic and epidemiological study of the 11th EVD outbreak. FINDINGS: Between May 19 and Sept 16, 2020, 130 EVD (119 confirmed and 11 probable) cases were reported across 13 Équateur Province health zones. The individual identified as the index case reported frequent consumption of bat meat, suggesting the outbreak started due to zoonotic spillover. Sequencing revealed two circulating Ebola virus variants associated with this outbreak-a Mbandaka variant associated with the majority (97%) of cases and a Tumba-like variant with similarity to the ninth EVD outbreak in 2018. The Tumba-like variant exhibited a reduced substitution rate, suggesting transmission from a previous survivor of EVD. INTERPRETATION: Integrating genetic and epidemiological data allowed for investigative fact-checking and verified patient-reported sources of possible zoonotic spillover. These results demonstrate that rapid genetic sequencing combined with epidemiological data can inform responders of the mechanisms of viral spread, uncover novel transmission modes, and provide a deeper understanding of the outbreak, which is ultimately needed for infection prevention and control during outbreaks. FUNDING: WHO and US Centers for Disease Control and Prevention. |
Antimicrobial resistance in multistate outbreaks of nontyphoidal Salmonella infections linked to animal contact-United States, 2015-2018
Frey E , Stapleton GS , Nichols MC , Gollarza LM , Birhane M , Chen JC , McCullough A , Carleton HA , Trees E , Hise KB , Tolar B , Francois Watkins L . J Clin Microbiol 2023 e0098123 Animal contact is an established risk factor for nontyphoidal Salmonella infections and outbreaks. During 2015-2018, the U.S. Centers for Disease Control and Prevention (CDC) and other U.S. public health laboratories began implementing whole-genome sequencing (WGS) of Salmonella isolates. WGS was used to supplement the traditional methods of pulsed-field gel electrophoresis for isolate subtyping, outbreak detection, and antimicrobial susceptibility testing (AST) for the detection of resistance. We characterized the epidemiology and antimicrobial resistance (AMR) of multistate salmonellosis outbreaks linked to animal contact during this time period. An isolate was considered resistant if AST yielded a resistant (or intermediate, for ciprofloxacin) interpretation to any antimicrobial tested by the CDC or if WGS showed a resistance determinant in its genome for one of these agents. We identified 31 outbreaks linked to contact with poultry (n = 23), reptiles (n = 6), dairy calves (n = 1), and guinea pigs (n = 1). Of the 26 outbreaks with resistance data available, we identified antimicrobial resistance in at least one isolate from 20 outbreaks (77%). Of 1,309 isolates with resistance information, 247 (19%) were resistant to ≥1 antimicrobial, and 134 (10%) were multidrug-resistant to antimicrobials from ≥3 antimicrobial classes. The use of resistance data predicted from WGS increased the number of isolates with resistance information available fivefold compared with AST, and 28 of 43 total resistance patterns were identified exclusively by WGS; concordance was high (>99%) for resistance determined by AST and WGS. The use of predicted resistance from WGS enhanced the characterization of the resistance profiles of outbreaks linked to animal contact by providing resistance information for more isolates. |
HantaNet: A new microbetrace application for hantavirus classification, genomic surveillance, epidemiology and outbreak investigations
Cintron R , Whitmer SLM , Moscoso E , Campbell EM , Kelly R , Talundzic E , Mobley M , Chiu KW , Shedroff E , Shankar A , Montgomery JM , Klena JD , Switzer WM . Viruses 2023 15 (11) Hantaviruses zoonotically infect humans worldwide with pathogenic consequences and are mainly spread by rodents that shed aerosolized virus particles in urine and feces. Bioinformatics methods for hantavirus diagnostics, genomic surveillance and epidemiology are currently lacking a comprehensive approach for data sharing, integration, visualization, analytics and reporting. With the possibility of hantavirus cases going undetected and spreading over international borders, a significant reporting delay can miss linked transmission events and impedes timely, targeted public health interventions. To overcome these challenges, we built HantaNet, a standalone visualization engine for hantavirus genomes that facilitates viral surveillance and classification for early outbreak detection and response. HantaNet is powered by MicrobeTrace, a browser-based multitool originally developed at the Centers for Disease Control and Prevention (CDC) to visualize HIV clusters and transmission networks. HantaNet integrates coding gene sequences and standardized metadata from hantavirus reference genomes into three separate gene modules for dashboard visualization of phylogenetic trees, viral strain clusters for classification, epidemiological networks and spatiotemporal analysis. We used 85 hantavirus reference datasets from GenBank to validate HantaNet as a classification and enhanced visualization tool, and as a public repository to download standardized sequence data and metadata for building analytic datasets. HantaNet is a model on how to deploy MicrobeTrace-specific tools to advance pathogen surveillance, epidemiology and public health globally. |
Micro‒global positioning systems for identifying nightly opportunities for Marburg virus spillover to humans by Egyptian Rousette bats
Amman BR , Schuh AJ , Akurut G , Kamugisha K , Namanya D , Sealy TK , Graziano JC , Enyel E , Wright EA , Balinandi S , Lutwama JJ , Kading RC , Atimnedi P , Towner JS . Emerg Infect Dis 2023 29 (11) 2238-2245 Marburg virus disease, caused by Marburg and Ravn orthomarburgviruses, emerges sporadically in sub-Saharan Africa and is often fatal in humans. The natural reservoir is the Egyptian rousette bat (ERB), which sheds virus in saliva, urine, and feces. Frugivorous ERBs discard test-bitten and partially eaten fruit, potentially leaving infectious virus behind that could be consumed by other susceptible animals or humans. Historically, 8 of 17 known Marburg virus disease outbreaks have been linked to human encroachment on ERB habitats, but no linkage exists for the other 9 outbreaks, raising the question of how bats and humans might intersect, leading to virus spillover. We used micro‒global positioning systems to identify nightly ERB foraging locations. ERBs from a known Marburg virus‒infected population traveled long distances to feed in cultivated fruit trees near homes. Our results show that ERB foraging behavior represents a Marburg virus spillover risk to humans and plausibly explains the origins of some past outbreaks. |
Identification and characterization of ten Escherichia coli strains encoding novel shiga toxin 2 subtypes, Stx2n as well as Stx2j, Stx2m, and Stx2o, in the United States
Lindsey RL , Prasad A , Feldgarden M , Gonzalez-Escalona N , Kapsak C , Klimke W , Melton-Celsa A , Smith P , Souvorov A , Truong J , Scheutz F . Microorganisms 2023 11 (10) The sharing of genome sequences in online data repositories allows for large scale analyses of specific genes or gene families. This can result in the detection of novel gene subtypes as well as the development of improved detection methods. Here, we used publicly available WGS data to detect a novel Stx subtype, Stx2n in two clinical E. coli strains isolated in the USA. During this process, additional Stx2 subtypes were detected; six Stx2j, one Stx2m strain, and one Stx2o, were all analyzed for variability from the originally described subtypes. Complete genome sequences were assembled from short- or long-read sequencing and analyzed for serotype, and ST types. The WGS data from Stx2n- and Stx2o-producing STEC strains were further analyzed for virulence genes pro-phage analysis and phage insertion sites. Nucleotide and amino acid maximum parsimony trees showed expected clustering of the previously described subtypes and a clear separation of the novel Stx2n subtype. WGS data were used to design OMNI PCR primers for the detection of all known stx1 (283 bp amplicon), stx2 (400 bp amplicon), intimin encoded by eae (221 bp amplicon), and stx2f (438 bp amplicon) subtypes. These primers were tested in three different laboratories, using standard reference strains. An analysis of the complete genome sequence showed variability in serogroup, virulence genes, and ST type, and Stx2 pro-phages showed variability in size, gene composition, and phage insertion sites. The strains with Stx2j, Stx2m, Stx2n, and Stx2o showed toxicity to Vero cells. Stx2j carrying strain, 2012C-4221, was induced when grown with sub-inhibitory concentrations of ciprofloxacin, and toxicity was detected. Taken together, these data highlight the need to reinforce genomic surveillance to identify the emergence of potential new Stx2 or Stx1 variants. The importance of this surveillance has a paramount impact on public health. Per our description in this study, we suggest that 2017C-4317 be designated as the Stx2n type-strain. |
A conceptual framework for nomenclatural stability and validity of medically important fungi: a proposed global consensus guideline for fungal name changes supported by ABP, ASM, CLSI, ECMM, ESCMID-EFISG, EUCAST-AFST, FDLC, IDSA, ISHAM, MMSA, and MSGERC
de Hoog S , Walsh TJ , Ahmed SA , Alastruey-Izquierdo A , Alexander BD , Arendrup MC , Babady E , Bai FY , Balada-Llasat JM , Borman A , Chowdhary A , Clark A , Colgrove RC , Cornely OA , Dingle TC , Dufresne PJ , Fuller J , Gangneux JP , Gibas C , Glasgow H , Gräser Y , Guillot J , Groll AH , Haase G , Hanson K , Harrington A , Hawksworth DL , Hayden RT , Hoenigl M , Hubka V , Johnson K , Kus JV , Li R , Meis JF , Lackner M , Lanternier F , Leal SM Jr , Lee F , Lockhart SR , Luethy P , Martin I , Kwon-Chung KJ , Meyer W , Nguyen MH , Ostrosky-Zeichner L , Palavecino E , Pancholi P , Pappas PG , Procop GW , Redhead SA , Rhoads DD , Riedel S , Stevens B , Sullivan KO , Vergidis P , Roilides E , Seyedmousavi A , Tao L , Vicente VA , Vitale RG , Wang QM , Wengenack NL , Westblade L , Wiederhold N , White L , Wojewoda CM , Zhang SX . J Clin Microbiol 2023 61 (11) e0087323 The rapid pace of name changes of medically important fungi is creating challenges for clinical laboratories and clinicians involved in patient care. We describe two sources of name change which have different drivers, at the species versus the genus level. Some suggestions are made here to reduce the number of name changes. We urge taxonomists to provide diagnostic markers of taxonomic novelties. Given the instability of phylogenetic trees due to variable taxon sampling, we advocate to maintain genera at the largest possible size. Reporting of identified species in complexes or series should where possible comprise both the name of the overarching species and that of the molecular sibling, often cryptic species. Because the use of different names for the same species will be unavoidable for many years to come, an open access online database of the names of all medically important fungi, with proper nomenclatural designation and synonymy, is essential. We further recommend that while taxonomic discovery continues, the adaptation of new name changes by clinical laboratories and clinicians be reviewed routinely by a standing committee for validation and stability over time, with reference to an open access database, wherein reasons for changes are listed in a transparent way. |
An improved framework for detecting discrete epidemiologically meaningful partitions in hierarchically clustered genetic data
Jacobson DK , Low R , Plucinski MM , Barratt JLN . Bioinform Adv 2023 3 (1) vbad118 MOTIVATION: Hierarchical clustering of microbial genotypes has the limitation that hierarchical clusters are nested, where smaller groups of related isolates exist within larger groups that get progressively larger as relationships become increasingly distant. In an epidemiologic context, investigators must dissect hierarchical trees into discrete groupings that are epidemiologically meaningful. We recently described a statistical framework (Method A) for dissecting hierarchical trees that attempts to minimize investigator bias. Here, we apply a modified version of that framework (Method B) to a hierarchical tree constructed from 2111 genotypes of the foodborne parasite Cyclospora, including 639 genotypes linked to epidemiologically defined outbreaks. To evaluate Method B's performance, we examined the concordance between these epidemiologically defined groupings and the genetic partitions identified. We also used the same epidemiologic clusters to evaluate the performance of Method A, plus two tree-dissection methods (cutreeHybrid and cutreeDynamic) available within the Dynamic Tree Cut R package, in addition to the TreeCluster method and PARNAS. RESULTS: Compared to the other methods, Method B, TreeCluster, and PARNAS were the most accurate (99.4%) in identifying genetic groups that reflected the epidemiologic groupings, noting that TreeCluster and PARNAS performed identically on our dataset. CutreeHybrid identified groups reflecting patterns in the wider Cyclospora population structure but lacked finer, strain-level discrimination (Simpson's D: cutreeHybrid=0.785). CutreeDynamic displayed good strain discrimination (Simpson's D = 0.933), though lacked sensitivity (77%). At two different threshold/radius settings TreeCluster/PARNAS displayed similar utility to Method B. However, Method B computes a tree-dissection threshold automatically, and the threshold/radius settings used when executing TreeCluster/PARNAS here were computed using Method B. Using a TreeCluster threshold of 0.045 as recommended in the TreeCluster documentation, epidemiologic utility dropped markedly below that of Method B. AVAILABILITY AND IMPLEMENTATION: Relevant code and data are publicly available. Source code (Method B) and instructions for its use are available here: https://github.com/Joel-Barratt/Hierarchical-tree-dissection-framework. |
Complexity of options related to restarting oral poliovirus vaccine (OPV) in national immunization programs after OPV cessation
Kalkowska DA , Wassilak SG , Wiesen E , FEstivariz C , Burns CC , Badizadegan K , Thompson KM . Gates Open Res 2023 7 55 Background: The polio eradication endgame continues to increase in complexity. With polio cases caused by wild poliovirus type 1 and circulating vaccine-derived polioviruses of all three types (1, 2 and 3) reported in 2022, the number, formulation, and use of poliovirus vaccines poses challenges for national immunization programs and vaccine suppliers. Prior poliovirus transmission modeling of globally-coordinated type-specific cessation of oral poliovirus vaccine (OPV) assumed creation of Sabin monovalent OPV (mOPV) stockpiles for emergencies and explored the potential need to restart OPV if the world reached a specified cumulative threshold number of cases after OPV cessation. Methods: We document the actual experience of type 2 OPV (OPV2) cessation and reconsider prior modeling assumptions related to OPV restart. We develop updated decision trees of national immunization options for poliovirus vaccines considering different possibilities for OPV restart. Results: While OPV restart represented a hypothetical situation for risk management and contingency planning to support the 2013-2018 Global Polio Eradication Initiative (GPEI) Strategic Plan, the actual epidemiological experience since OPV2 cessation raises questions about what, if any, trigger(s) could lead to restarting the use of OPV2 in routine immunization and/or plans for potential future restart of type 1 and 3 OPV after their respective cessation. The emergency use listing of a genetically stabilized novel type 2 OPV (nOPV2) and continued evaluation of nOPV for types 1 and/or 3 add further complexity by increasing the combinations of possible OPV formulations for OPV restart. Conclusions: Expanding on a 2019 discussion of the logistical challenges and implications of restarting OPV, we find a complex structure of the many options and many issues related to OPV restart decisions and policies as of early 2023. We anticipate many challenges for forecasting prospective vaccine supply needs during the polio endgame due to increasing potential combinations of poliovirus vaccine choices. |
MicrobeTrace: Retooling Molecular Epidemiology for Rapid Public Health Response (preprint)
Campbell EM , Boyles A , Shankar A , Kim J , Knyazev S , Switzer WM . bioRxiv 2020 2020.07.22.216275 Motivation Outbreak investigations use data from interviews, healthcare providers, laboratories and surveillance systems. However, integrated use of data from multiple sources requires a patchwork of software that present challenges in usability, interoperability, confidentiality, and cost. Rapid integration, visualization and analysis of data from multiple sources can guide effective public health interventions.Results We developed MicrobeTrace to facilitate rapid public health responses by overcoming barriers to data integration and exploration in molecular epidemiology. Using publicly available HIV sequences and other data, we demonstrate the analysis of viral genetic distance networks and introduce a novel approach to minimum spanning trees that simplifies results. We also illustrate the potential utility of MicrobeTrace in support of contact tracing by analyzing and displaying data from an outbreak of SARS-CoV-2 in South Korea in early 2020.Availability and Implementation MicrobeTrace is a web-based, client-side, JavaScript application (https://microbetrace.cdc.gov) that runs in Chromium-based browsers and remains fully-operational without an internet connection. MicrobeTrace is developed and actively maintained by the Centers for Disease Control and Prevention. The source code is available at https://github.com/cdcgov/microbetrace.Contact ells{at}cdc.govCompeting Interest StatementThe authors have declared no competing interest. |
Transcriptome Analysis of Neisseria gonorrhoeae During Natural Infection Reveals Differential Expression of Antibiotic Resistance Determinants Between Men and Women (preprint)
Nudel K , McClure R , Moreau M , Briars E , Abrams AJ , Tjaden B , Su XH , Trees D , Rice PA , Massari P , Genco CA . bioRxiv 2018 319970 Neisseria gonorrhoeae is a bacterial pathogen responsible for the sexually transmitted infection, gonorrhea. Emergence of antimicrobial resistance (AMR) of N. gonorrhoeae worldwide has resulted in limited therapeutic choices for this infection. Men who seek treatment often have symptomatic urethritis; in contrast, gonococcal cervicitis in women is usually minimally symptomatic, but may progress to pelvic inflammatory disease. Previously, we reported the first analysis of gonococcal transcriptome expression determined in secretions from women with cervical infection. Here, we defined gonococcal global transcriptional responses in urethral specimens from men with symptomatic urethritis and compared these with transcriptional responses in specimens obtained from women with cervical infections, and of in vitro-grown N. gonorrhoeae isolates. This is the first comprehensive comparison of gonococcal gene expression in infected men and women. RNA sequencing analysis revealed that 9.4% of gonococcal genes showed increased expression exclusively in men and included genes involved in host immune cell interactions and 4.3% showed increased expression exclusively in women and included phage-associated genes. Infected men and women displayed comparable antibiotic resistant-genotypes and in vitro –phenotypes, but a 4-fold higher expression of the Mtr efflux pump-related genes was observed in men. These results suggest that expression of AMR genes is programmed genotypically, and also driven by sex-specific environments. Collectively, our results indicate that distinct N. gonorrhoeae gene expression signatures are detected during genital infection in men and women. We propose that therapeutic strategies could target sex specific differences in expression of antibiotic resistance genes. |
Mechanistic basis for decreased antimicrobial susceptibility in a clinical isolate of Neisseria gonorrhoeae possessing a mosaic-like mtr efflux pump locus (preprint)
Rouquette-Loughlin CE , Reimche JL , Balthazar JT , Dhulipala V , Gernert KM , Kersh EN , Pham CD , Pettus K , Abrams AJ , Trees DL , St Cyr S , Shafer WM . bioRxiv 2018 448712 Recent reports suggest that mosaic-like sequences within the mtr (multiple transferable resistance) efflux pump locus of Neisseria gonorrhoeae likely originating from commensal Neisseria sp. by transformation can increase the ability of gonococci to resist structurally diverse antimicrobials. Thus, acquisition of numerous nucleotide changes within the mtrR gene encoding the transcriptional repressor (MtrR) of the mtrCDE efflux pump-encoding operon or overlapping promoter region for both along with those that cause amino acid changes in the MtrD transporter protein were recently reported to decrease gonococcal susceptibility to numerous antimicrobials, including azithromycin (Azi) (Wadsworth et al. 2018. MBio. doi.org/10.1128/mBio.01419-18). We performed detailed genetic and molecular studies to define the mechanistic basis for why such strains can exhibit decreased susceptibility to MtrCDE antimicrobial substrates including Azi. We report that a strong cis-acting transcriptional impact of a single nucleotide change within the -35 hexamer of the mtrCDE promoter as well gain-of-function amino acid changes at the C-terminal region of MtrD can mechanistically account for the decreased antimicrobial susceptibility of gonococci with a mosaic-like mtr locus.IMPORTANCE Historically, after introduction of an antibiotic for treatment of gonorrhea, strains of N. gonorrhoeae emerge that display clinical resistance due to spontaneous mutation or acquisition of resistance genes. Genetic exchange between members of the Neisseria genus occurring by transformation can cause significant changes in gonococci that impact the structure of an antibiotic target or expression of genes involved in resistance. The results presented herein provide a framework for understanding how mosaic-like DNA sequences from commensal Neisseria that recombine within the gonococcal mtr efflux pump locus function to decrease bacterial susceptibility to antimicrobials including antibiotics used in therapy of gonorrhea. |
Guiding Vaccine Efficacy Trial Design During Public Health Emergencies: An interactive web-based decision support tool (preprint)
Bellan SE , Eggo RM , Gsell PS , Kucharski AJ , Dean NE , Donohue R , Zook M , Odhiambo F , Longini IM Jr , Brisson M , Mahon BE , Henao-Restrepo AM . bioRxiv 2018 252783 The design and execution of rigorous, fast, and ethical vaccine efficacy trials can be challenging during epidemics of emerging pathogens, such as the 2014-2016 Ebola virus and 2015-2016 Zika virus epidemics. Response to an urgent public health crisis requires accelerated research even as emerging epidemics themselves change rapidly and are inherently less well understood than well-established diseases. As part of the World Health Organization Research and Development Blueprint, we designed a web-based interactive decision support system (InterVax-Tool) to help diverse stakeholders navigate the epidemiological, logistical, and ethical decisions involved in designing a vaccine efficacy trial during a public health emergency. In contrast to existing literature on trial design, InterVax-Tool offers high-level visual and interactive assistance through a set of four decision trees, guiding users through selection of 1) the Primary Endpoint, (2) the Target Population, (3) Randomization, and (4) the Comparator. Guidance is provided on how each of fourteen key considerations–grouped as Epidemiological, Vaccine-related, Infrastructural, or Sociocultural–should be used to inform each decision in the trial design process. The tool is not intended to provide a black box decision framework for identifying an optimal trial design, but rather to facilitate transparent, collaborative and comprehensive discussion of the relevant decisions, while recording the decision process. The tool can also assist capacity building by providing a cross-disciplinary picture of trial design using concepts from epidemiology, study design, vaccinology, biostatistics, mathematical modeling and clinical research ethics. Here, we describe the goals and features of InterVax-Tool as well as its application to the design of a Zika vaccine efficacy trial.One Sentence Summary An interactive web-based decision support tool was developed to assist in the design of vaccine efficacy trials during emerging outbreaks. |
SARS-CoV-2 genomic diversity in households highlights the challenges of sequence-based transmission inference (preprint)
Bendall E , Paz-Bailey G , Santiago GA , Porucznik CA , Stanford JB , Stockwell MS , Duque J , Jeddy Z , Veguilla V , Major C , Rivera-Amill V , Rolfes MA , Dawood FS , Lauring AS . medRxiv 2022 10 (6) e0040022 Background: The reliability of sequence-based inference of SARS-CoV-2 transmission is not clear. Sequence data from infections among household members can define the expected genomic diversity of a virus along a defined transmission chain. Method(s): SARS-CoV-2 cases were identified prospectively among 2,369 participants in 706 households. Specimens with an RT-PCR cycle threshold <=30 underwent whole genome sequencing. Intrahost single nucleotide variants (iSNV) were identified at >=5% frequency. Phylogenetic trees were used to evaluate the relationship of household and community sequences. Result(s): There were 178 SARS-CoV-2 cases in 706 households. Among 147 specimens sequenced, 106 yielded a whole genome consensus with coverage suitable for identifying iSNV. Twenty-six households had sequences from multiple cases within 14 days. Consensus sequences were indistinguishable among cases in 15 households, while 11 had >1 consensus that differed by 1-2 mutations. Sequences from households and the community were often interspersed on phylogenetic trees. Identification of iSNV improved inference in 2 of 15 households with indistinguishable consensus sequences and 6 of 11 with distinct ones. Conclusion(s): In multiple infection households, whole genome consensus sequences differed by 0-1 mutations. Identification of shared iSNV occasionally resolved linkage, but the low genomic diversity of SARS-CoV-2 limits the utility of "sequence-only" transmission inference. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
High-resolution characterization of recent tuberculosis transmission in Botswana using geospatial and genomic data - the Kopanyo Study (preprint)
Baker CR , Barilar I , de Araujo LS , Rimoin AW , Parker DM , Boyd R , Tobias JL , Moonan PK , Click ES , Finlay A , Oeltmann JE , Minin VN , Modongo C , Zetola NM , Niemann S , Shin SS . medRxiv 2022 18 Introduction. Combining genomic and geospatial data can be useful for understanding Mycobacterium tuberculosis (Mtb) transmission in high tuberculosis burden settings. Methods. We performed whole genome sequencing (WGS) on Mtb DNA extracted from sputum cultures from a population-based tuberculosis study conducted in 2012-2016 in Gaborone, Botswana. We used kernel density estimation, spatial K-functions, and created spatial distributions of phylogenetic trees. WGS-based clusters of isolates <5 single nucleotide polymorphisms were considered recent transmission, and large WGS-based clusters (>10 members) were considered outbreaks. Results. We analyzed data from 1449 participants with culture-confirmed TB. Among these, 946 (65%) participants had both molecular and geospatial data. A total of 62 belonged to five large outbreaks (10-19 participants each). Geospatial clustering was detected in two of the five large outbreaks, suggesting heterogeneous spatial patterns within the community. Conclusions. Integration of genomic and geospatial data identified distinct patterns of tuberculosis transmission in a high-tuberculosis burden setting. Targeted interventions in these smaller geographies may interrupt on-going transmission. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
Evaluation of the Illumina iSeq whole genome sequencing system for enteric disease surveillance and outbreak detection
Trees E , Poates A , Sabol A , LaFon P , Truong J , Lindsey R . J Microbiol Methods 2023 211 106784 The Illumina iSeq low-capacity sequencing platform was evaluated for use in foodborne disease surveillance and outbreak detection. The platform produced high quality sequence data comparable to that of the Illumina MiSeq and was cost-effective with fast turn-around time in low sample volume environments. |
Pollen and asthma morbidity in Atlanta: A 26-year time-series study
Lappe BL , Ebelt S , D'Souza RR , Manangan A , Brown C , Saha S , Harris D , Chang HH , Sole A , Scovronick N . Environ Int 2023 177 107998 BACKGROUND: Compared to many environmental risk factors, the relationship between pollen and asthma is understudied, including how associations may differ by pollen type and between subgroups, and how associations may be changing over time. OBJECTIVES: We evaluated the association between ambient pollen concentrations and emergency department (ED) visits for asthma and wheeze in Atlanta, Georgia during 1993-2018. We estimated overall associations for 13 individual pollen taxa, as well as associations by decade, race, age (5-17, 18-64, 65+), and insurance status (Medicaid vs non-Medicaid). METHODS: Speciated pollen data were acquired from Atlanta Allergy & Asthma, a nationally certified pollen counting station. ED visit data were obtained from individual hospitals and from the Georgia Hospital Association. We performed time-series analyses using quasi-Poisson distributed lag models, with primary analyses assessing 3-day (lag 0-2 days) pollen levels. Models controlled for day of week, holidays, air temperature, month, year, and month-by-year interactions. RESULTS: From 1993 to 2018, there were 686,259 ED visits for asthma and wheeze in the dataset, and the number of ED visits increased over time. We observed positive associations of asthma and wheeze ED visits with nine of the 13 pollen taxa: trees (maple, birch, pine, oak, willow, sycamore, and mulberry), two weeds (nettle and pigweed), and grasses. Rate ratios indicated 1-8% increases in asthma and wheeze ED visits per standard deviation increases in pollen. In general, we observed stronger associations in the earliest period (1993-2000), in younger people, and in Black patients; however, results varied by pollen taxa. CONCLUSIONS: Some, but not all, types of pollen are associated with increased ED visits for asthma/wheeze. Associations are generally higher in Black and younger patients and appear to have decreased over time. |
Costs, health benefits, and cost-effectiveness of chlamydia screening and partner notification in the United States, 2000-2019: A mathematical modeling analysis
Rönn MM , Li Y , Gift TL , Chesson HW , Menzies NA , Hsu K , Salomon JA . Sex Transm Dis 2023 50 (6) 351-358 BACKGROUND: Chlamydia remains a significant public health problem that contributes to adverse reproductive health outcomes. In the United States, sexually active women 24 years and younger are recommended to receive annual screening for chlamydia. In this study, we evaluated the impact of estimated current levels of screening and partner notification (PN), and the impact of screening based on guidelines on chlamydia associated sequelae, quality adjusted life years (QALYs) lost and costs. METHODS: We conducted a cost-effectiveness analysis of chlamydia screening, using a published calibrated pair formation transmission model that estimated trends in chlamydia screening coverage in the United States from 2000 to 2015 consistent with epidemiological data. We used probability trees to translate chlamydial infection outcomes into estimated numbers of chlamydia-associated sequelae, QALYs lost, and health care services costs (in 2020 US dollars). We evaluated the costs and population health benefits of screening and PN in the United States for 2000 to 2015, as compared with no screening and no PN. We also estimated the additional benefits that could be achieved by increasing screening coverage to the levels indicated by the policy recommendations for 2016 to 2019, compared with screening coverage achieved by 2015. RESULTS: Screening and PN from 2000 to 2015 were estimated to have averted 1.3 million (95% uncertainty interval [UI] 490,000-2.3 million) cases of pelvic inflammatory disease, 430,000 (95% UI, 160,000-760,000) cases of chronic pelvic pain, 300,000 (95% UI, 104,000-570,000) cases of tubal factor infertility, and 140,000 (95% UI, 47,000-260,000) cases of ectopic pregnancy in women. We estimated that chlamydia screening and PN cost $9700 per QALY gained compared with no screening and no PN. We estimated the full realization of chlamydia screening guidelines for 2016 to 2019 to cost $30,000 per QALY gained, compared with a scenario in which chlamydia screening coverage was maintained at 2015 levels. DISCUSSION: Chlamydia screening and PN as implemented in the United States from 2000 through 2015 has substantially improved population health and provided good value for money when considering associated health care services costs. Further population health gains are attainable by increasing screening further, at reasonable cost per QALY gained. |
Comparing genomic variant identification protocols for Candida auris
Li X , Muñoz JF , Gade L , Argimon S , Bougnoux ME , Bowers JR , Chow NA , Cuesta I , Farrer RA , Maufrais C , Monroy-Nieto J , Pradhan D , Uehling J , Vu D , Yeats CA , Aanensen DM , d'Enfert C , Engelthaler DM , Eyre DW , Fisher MC , Hagen F , Meyer W , Singh G , Alastruey-Izquierdo A , Litvintseva AP , Cuomo CA . Microb Genom 2023 9 (4) Genomic analyses are widely applied to epidemiological, population genetic and experimental studies of pathogenic fungi. A wide range of methods are employed to carry out these analyses, typically without including controls that gauge the accuracy of variant prediction. The importance of tracking outbreaks at a global scale has raised the urgency of establishing high-accuracy pipelines that generate consistent results between research groups. To evaluate currently employed methods for whole-genome variant detection and elaborate best practices for fungal pathogens, we compared how 14 independent variant calling pipelines performed across 35 Candida auris isolates from 4 distinct clades and evaluated the performance of variant calling, single-nucleotide polymorphism (SNP) counts and phylogenetic inference results. Although these pipelines used different variant callers and filtering criteria, we found high overall agreement of SNPs from each pipeline. This concordance correlated with site quality, as SNPs discovered by a few pipelines tended to show lower mapping quality scores and depth of coverage than those recovered by all pipelines. We observed that the major differences between pipelines were due to variation in read trimming strategies, SNP calling methods and parameters, and downstream filtration criteria. We calculated specificity and sensitivity for each pipeline by aligning three isolates with chromosomal level assemblies and found that the GATK-based pipelines were well balanced between these metrics. Selection of trimming methods had a greater impact on SAMtools-based pipelines than those using GATK. Phylogenetic trees inferred by each pipeline showed high consistency at the clade level, but there was more variability between isolates from a single outbreak, with pipelines that used more stringent cutoffs having lower resolution. This project generated two truth datasets useful for routine benchmarking of C. auris variant calling, a consensus VCF of genotypes discovered by 10 or more pipelines across these 35 diverse isolates and variants for 2 samples identified from whole-genome alignments. This study provides a foundation for evaluating SNP calling pipelines and developing best practices for future fungal genomic studies. |
Optimizing hierarchical tree dissection parameters using historic epidemiologic data as 'ground truth'.
Jacobson D , Barratt J . PLoS One 2023 18 (2) e0282154 Hierarchical clustering of pathogen genotypes is widely used to complement epidemiologic investigations of outbreaks. Investigators must dissect trees to obtain genetic partitions that provide epidemiologists with meaningful information. Statistical approaches to tree dissection often require a user-defined parameter to predict the optimal partition number and augmenting this parameter can drastically impact resultant partition memberships. Here, we demonstrate how to optimize a given tree dissection parameter to maximize accuracy irrespective of the tree dissection method used. We hierarchically clustered 1,873 genotypes of the foodborne pathogen Cyclospora spp., including 587 possessing links to historic outbreaks. We dissected the resulting tree using a statistical method requiring users to select the value of a 'stringency parameter' (s), with a recommended value of 95% to 99.5%. We dissected this hierarchical tree across s-values from 94% to 99.5% (at increments of 0.25%), to identify a value that maximized partitioning accuracy, defined as the degree to which genetic partitions conform to known epidemiologic groupings. We show that s-values of 96.5% and 96.75% yield the highest accuracy (> 99.9%) when clustering Cyclospora sp. isolates with known epidemiologic linkages. In practice, the optimized s-value will generate robust genetic partitions comprising isolates likely derived from a common food source, even when the epidemiologic grouping is not known prior to genetic clustering. While the s-value is specific to the tree dissection method used here, the optimization approach described could be applied to any parameter/method used to dissect hierarchical trees. |
Lifetime quality-adjusted life years lost due to genital herpes acquired in the United States in 2018: a mathematical modeling study
You S , Yaesoubi R , Lee K , Li Y , Eppink ST , Hsu KK , Chesson HW , Gift TL , Berruti AA , Salomon JA , Rönn MM . Lancet Reg Health Am 2023 19 100427 Background: Genital herpes (GH), caused by herpes simplex virus type 1 and type 2 (HSV-1, HSV-2), is a common sexually transmitted disease associated with adverse health outcomes. Symptoms associated with GH outbreaks can be reduced by antiviral medications, but the infection is incurable and lifelong. In this study, we estimate the long-term health impacts of GH in the United States using quality-adjusted life years (QALYs) lost. Methods: We used probability trees to model the natural history of GH secondary to infection with HSV-1 and HSV-2 among people aged 18–49 years. We modelled the following outcomes to quantify the major causes of health losses following infection: symptomatic herpes outbreaks, psychosocial impacts associated with diagnosis and recurrences, urinary retention caused by sacral radiculitis, aseptic meningitis, Mollaret's meningitis, and neonatal herpes. The model was parameterized based on published literature on the natural history of GH. We summarized losses of health by computing the lifetime number of QALYs lost per genital HSV-1 and HSV-2 infection, and we combined this information with incidence estimates to compute the total lifetime number of QALYs lost due to infections acquired in 2018 in the United States. Findings: We estimated 0.05 (95% uncertainty interval (UI) 0.02–0.08) lifetime QALYs lost per incident GH infection acquired in 2018, equivalent to losing 0.05 years or about 18 days of life for one person with perfect health. The average number of QALYs lost per GH infection due to genital HSV-1 and HSV-2 was 0.01 (95% UI 0.01–0.02) and 0.05 (95% UI 0.02–0.09), respectively. The burden of genital HSV-1 is higher among women, while the burden of HSV-2 is higher among men. QALYs lost per neonatal herpes infection was estimated to be 7.93 (95% UI 6.63–9.19). At the population level, the total estimated lifetime QALYs lost as a result of GH infections acquired in 2018 was 33,100 (95% UI 12,600–67,900) due to GH in adults and 3,140 (95% UI 2,260–4,140) due to neonatal herpes. Results were most sensitive to assumptions on the magnitude of the disutility associated with post-diagnosis psychosocial distress and symptomatic recurrences. Interpretation: GH is associated with substantial health losses in the United States. Results from this study can be used to compare the burden of GH to other diseases, and it provides inputs that may be used in studies on the health impact and cost-effectiveness of interventions that aim to reduce the burden of GH. Funding: The Center for Disease Control and Prevention © 2023 The Author(s) |
Epidemiologic utility of a framework for partition number selection when dissecting hierarchically clustered genetic data evaluated on the intestinal parasite Cyclospora cayetanensis.
Barratt JLN , Plucinski MM . Am J Epidemiol 2023 192 (5) 772-781 Comparing parasite genotypes to inform parasitic disease outbreak investigations involves computation of genetic distances that are typically analyzed by hierarchical clustering to identify related isolates, indicating a common source. A limitation of hierarchical clustering is that hierarchical clusters are not discrete, they are nested. Consequently, small groups of similar isolates exist within larger groups that get progressively larger as relationships become increasingly distant. Investigators must dissect hierarchical trees at a partition number ensuring grouped isolates belong to the same strain; a process typically performed subjectively, introducing bias into resultant groupings. We describe an unbiased, probabilistic framework for partition number selection that ensures partitions comprise isolates that are statistically likely to belong to the same strain. We compute distances and establish a normalized distribution of background distances that is used to demarcate a threshold below which the closeness of relationships is unlikely to be random. Distances are hierarchically clustered and the dendrogram dissected at a partition number where most within-partition distances fall below the threshold. We evaluated this framework by partitioning 1,137 clustered Cyclospora cayetanensis genotypes including 552 isolates epidemiologically linked to various outbreaks. The framework was 91% sensitive and 100% specific in assigning epidemiologically-linked isolates to the same partition. |
Observations from the USA National Phenology Network can be leveraged to model airborne pollen
Katz DSW , Vogt E , Manangan A , Brown CL , Dalan D , Zhu K , Song Y , Crimmins TM . Aerobiologia (Bologna) 2022 The USA National Phenology Network (USA-NPN) hosts the largest volunteer-contributed collection of plant phenology observations in the USA. The potential contributions of these spatially and temporally explicit observations of flowers and pollen cones to the field of aerobiology remain largely unexplored. Here, we introduce this freely available dataset and demonstrate its prospective applications for modeling airborne pollen in a case study. Specifically, we compare the timing of 4265 observations of flowering for oak (Quercus) trees in the eastern USA to winter–spring temperatures. We then use this relationship to predict the day of peak flowering at 15 pollen monitoring stations in 15 years and compare the predicted day of peak flowering to the peak day of measured pollen (n = 111 station-years). There was a strong association between winter–spring temperature and the presence of open flowers (r2 = 0.66, p < 0.0001) and the predicted peak flowering was strongly correlated with peak airborne pollen concentrations (r2 = 0.81, p < 0.0001). These results demonstrate the potential for the USA-NPN’s phenological observations to underpin source-based models of airborne pollen. We also highlight opportunities for leveraging and enhancing this near real-time dataset for aerobiological applications. © 2022, The Author(s), under exclusive licence to Springer Nature B.V. |
SARS-CoV-2 Genomic Diversity in Households Highlights the Challenges of Sequence-Based Transmission Inference.
Bendall EE , Paz-Bailey G , Santiago GA , Porucznik CA , Stanford JB , Stockwell MS , Duque J , Jeddy Z , Veguilla V , Major C , Rivera-Amill V , Rolfes MA , Dawood FS , Lauring AS . mSphere 2022 7 (6) e0040022 The reliability of sequence-based inference of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission is not clear. Sequence data from infections among household members can define the expected genomic diversity of a virus along a defined transmission chain. SARS-CoV-2 cases were identified prospectively among 2,369 participants in 706 households. Specimens with a reverse transcription-PCR cycle threshold of ≤30 underwent whole-genome sequencing. Intrahost single-nucleotide variants (iSNV) were identified at a ≥5% frequency. Phylogenetic trees were used to evaluate the relationship of household and community sequences. There were 178 SARS-CoV-2 cases in 706 households. Among 147 specimens sequenced, 106 yielded a whole-genome consensus with coverage suitable for identifying iSNV. Twenty-six households had sequences from multiple cases within 14 days. Consensus sequences were indistinguishable among cases in 15 households, while 11 had ≥1 consensus sequence that differed by 1 to 2 mutations. Sequences from households and the community were often interspersed on phylogenetic trees. Identification of iSNV improved inference in 2 of 15 households with indistinguishable consensus sequences and in 6 of 11 with distinct ones. In multiple-infection households, whole-genome consensus sequences differed by 0 to 1 mutations. Identification of shared iSNV occasionally resolved linkage, but the low genomic diversity of SARS-CoV-2 limits the utility of "sequence-only" transmission inference. IMPORTANCE We performed whole-genome sequencing of SARS-CoV-2 from prospectively identified cases in three longitudinal household cohorts. In a majority of multi-infection households, SARS-CoV-2 consensus sequences were indistinguishable, and they differed by 1 to 2 mutations in the rest. Importantly, even with modest genomic surveillance of the community (3 to 5% of cases sequenced), it was not uncommon to find community sequences interspersed with household sequences on phylogenetic trees. Identification of shared minority variants only occasionally resolved these ambiguities in transmission linkage. Overall, the low genomic diversity of SARS-CoV-2 limits the utility of "sequence-only" transmission inference. Our work highlights the need to carefully consider both epidemiologic linkage and sequence data to define transmission chains in households, hospitals, and other transmission settings. |
Predicting Plasmodium falciparum infection status in blood using a multiplexed bead-based antigen detection assay and machine learning approaches.
Schmedes SE , Dimbu RP , Steinhardt L , Lemoine JF , Chang MA , Plucinski M , Rogier E . PLoS One 2022 17 (9) e0275096 BACKGROUND: Plasmodium blood-stage infections can be identified by assaying for protein products expressed by the parasites. While the binary result of an antigen test is sufficient for a clinical result, greater nuance can be gathered for malaria infection status based on quantitative and sensitive detection of Plasmodium antigens and machine learning analytical approaches. METHODS: Three independent malaria studies performed in Angola and Haiti enrolled persons at health facilities and collected a blood sample. Presence and parasite density of P. falciparum infection was determined by microscopy for a study in Angola in 2015 (n = 193), by qRT-PCR for a 2016 study in Angola (n = 208), and by qPCR for a 2012-2013 Haiti study (n = 425). All samples also had bead-based detection and quantification of three Plasmodium antigens: pAldolase, pLDH, and HRP2. Decision trees and principal component analysis (PCA) were conducted in attempt to categorize P. falciparum parasitemia density status based on continuous antigen concentrations. RESULTS: Conditional inference trees were trained using the known P. falciparum infection status and corresponding antigen concentrations, and PCR infection status was predicted with accuracies ranging from 73-96%, while level of parasite density was predicted with accuracies ranging from 59-72%. Multiple decision nodes were created for both pAldolase and HRP2 antigens. For all datasets, dichotomous infectious status was more accurately predicted when compared to categorization of different levels of parasite densities. PCA was able to account for a high level of variance (>80%), and distinct clustering was found in both dichotomous and categorical infection status. CONCLUSIONS: This pilot study offers a proof-of-principle of the utility of machine learning approaches to assess P. falciparum infection status based on continuous concentrations of multiple Plasmodium antigens. |
Evaluation of various distance computation methods for construction of haplotype-based phylogenies from large MLST dataset.
Jacobson D , Zheng Y , Plucinski MM , Qvarnstrom Y , Barratt JLN . Mol Phylogenet Evol 2022 177 107608 Multi-locus sequence typing (MLST) is widely used to investigate genetic relationships among eukaryotic taxa, including parasitic pathogens. MLST analysis workflows typically involve construction of alignment-based phylogenetic trees - i.e., where tree structures are computed from nucleotide differences observed in a multiple sequence alignment (MSA). Notably, alignment-based phylogenetic methods require that all isolates/taxa are represented by a single sequence. When multiple loci are sequenced these sequences may be concatenated to produce one tree that includes information from all loci. Alignment-based phylogenetic techniques are robust and widely used yet possess some shortcomings, including how heterozygous sites are handled, intolerance for missing data (i.e., partial genotypes), and differences in the way insertions-deletions (indels) are scored/treated during tree construction. In certain contexts, 'haplotype-based' methods may represent a viable alternative to alignment-based techniques, as they do not possess the aforementioned limitations. This is namely because haplotype-based methods assess genetic similarity based on numbers of shared (i.e., intersecting) haplotypes as opposed to similarities in nucleotide composition observed in an MSA. For haplotype-based comparisons, choosing an appropriate distance statistic is fundamental, and several statistics are available to choose from. However, a comprehensive assessment of various available statistics for their ability to produce a robust haplotype-based phylogenetic reconstruction has not yet been performed. We evaluated seven distance statistics by applying them to extant MLST datasets from the gastrointestinal parasite Cyclospora cayetanensis and two species of pathogenic nematode of the genus Strongyloides. We compare the genetic relationships identified using each statistic to epidemiologic, geographic, and host metadata. We show that Barratt's heuristic definition of genetic distance was the most robust among the statistics evaluated. Consequently, it is proposed that Barratt's heuristic represents a useful approach for use in the context of challenging MLST datasets possessing features (i.e., high heterozygosity, partial genotypes, and indel or repeat-based polymorphisms) that confound or preclude the use of alignment-based methods. |
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