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39 result(s) for "Domman, Daryl"
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Global landscape of SARS-CoV-2 genomic surveillance and data sharing
Genomic surveillance has shaped our understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. We performed a global landscape analysis on SARS-CoV-2 genomic surveillance and genomic data using a collection of country-specific data. Here, we characterize increasing circulation of the Alpha variant in early 2021, subsequently replaced by the Delta variant around May 2021. SARS-CoV-2 genomic surveillance and sequencing availability varied markedly across countries, with 45 countries performing a high level of routine genomic surveillance and 96 countries with a high availability of SARS-CoV-2 sequencing. We also observed a marked heterogeneity of sequencing percentage, sequencing technologies, turnaround time and completeness of released metadata across regions and income groups. A total of 37% of countries with explicit reporting on variants shared less than half of their sequences of variants of concern (VOCs) in public repositories. Our findings indicate an urgent need to increase timely and full sharing of sequences, the standardization of metadata files and support for countries with limited sequencing and bioinformatics capacity. Analyses on the global diversity of SARS-CoV-2 genomic surveillance across 118 countries and the extent of public availability of genomic data provide evidence to better inform SARS-CoV-2 surveillance policy.
Genomic characterization of Staphylococcus aureus isolates causing osteoarticular infections in otherwise healthy children
Pediatric osteoarticular infections are commonly caused by Staphylococcus aureus. The contribution of S. aureus genomic variability to pathogenesis of these infections is poorly described. We prospectively enrolled 47 children over 3 1/2 years from whom S. aureus was isolated on culture-12 uninfected with skin colonization, 16 with skin abscesses, 19 with osteoarticular infections (four with septic arthritis, three with acute osteomyelitis, six with acute osteomyelitis and septic arthritis and six with chronic osteomyelitis). Isolates underwent whole genome sequencing, with assessment for 254 virulence genes and any mutations as well as creation of a phylogenetic tree. Finally, isolates were compared for their ability to form static biofilms and compared to the genetic analysis. No sequence types predominated amongst osteoarticular infections. Only genes involved in evasion of host immune defenses were more frequently carried by isolates from osteoarticular infections than from skin colonization (p = .02). Virulence gene mutations were only noted in 14 genes (three regulating biofilm formation) when comparing isolates from subjects with osteoarticular infections and those with skin colonization. Biofilm results demonstrated large heterogeneity in the isolates' capacity to form static biofilms, with healthy control isolates producing more robust biofilm formation. S. aureus causing osteoarticular infections are genetically heterogeneous, and more frequently harbor genes involved in immune evasion than less invasive isolates. However, virulence gene carriage overall is similar with infrequent mutations, suggesting that pathogenesis of S. aureus osteoarticular infections may be primarily regulated at transcriptional and/or translational levels.
Highly Resistant Cholera Outbreak Strain in Zimbabwe
Whole genomes of 11 Vibrio cholerae O1 isolates from the 2018–2019 outbreak in Zimbabwe were sequenced to investigate the determinants of antimicrobial resistance and their phylogenetic relationships to 1200 global seventh-cholera-pandemic genomes.
Choclo virus (CHOV) recovered from deep metatranscriptomics of archived frozen tissues in natural history biorepositories
Hantaviruses are negative-stranded RNA viruses that can sometimes cause severe disease in humans; however, they are maintained in mammalian host populations without causing harm. In Panama, sigmodontine rodents serve as hosts to transmissible hantaviruses. Due to natural and anthropogenic forces, these rodent populations are having increased contact with humans. We extracted RNA and performed Illumina deep metatranscriptomic sequencing on Orthohantavirus seropositive museum tissues from rodents. We acquired sequence reads mapping to Choclo virus (CHOV, Orthohantavirus chocloense) from heart and kidney tissue of a two-decade old frozen museum sample from a Costa Rican pygmy rice rat (Oligoryzomys costaricensis) collected in Panama. Reads mapped to the CHOV reference were assembled and then validated by visualization of the mapped reads against the assembly. We recovered a 91% complete consensus sequence from a reference-guided assembly to CHOV with an average of 16X coverage. The S and M segments used in our phylogenetic analyses were nearly complete (98% and 99%, respectively). There were 1,199 ambiguous base calls of which 93% were present in the L segment. Our assembled genome varied 1.1% from the CHOV reference sequence resulting in eight nonsynonymous mutations. Further analysis of all publicly available partial S segment sequences support a clear relationship between CHOV clinical cases and O. costaricensis acquired strains. Viruses occurring at extremely low abundances can be recovered from deep metatranscriptomics of archival tissues housed in research natural history museum biorepositories. Our efforts resulted in the second CHOV genome publicly available. This genomic data is important for future surveillance and diagnostic tools as well as understanding the evolution and pathogenicity of CHOV.
Integrated view of Vibrio cholerae in the Americas
Latin America has experienced two of the largest cholera epidemics in modern history; one in 1991 and the other in 2010. However, confusion still surrounds the relationships between globally circulating pandemic Vibrio cholerae clones and local bacterial populations. We used whole-genome sequencing to characterize cholera across the Americas over a 40-year time span. We found that both epidemics were the result of intercontinental introductions of seventh pandemic El Tor V. cholerae and that at least seven lineages local to the Americas are associated with disease that differs epidemiologically from epidemic cholera. Our results consolidate historical accounts of pandemic cholera with data to show the importance of local lineages, presenting an integrated view of cholera that is important to the design of future disease control strategies.
Genomics of the Argentinian cholera epidemic elucidate the contrasting dynamics of epidemic and endemic Vibrio cholerae
In order to control and eradicate epidemic cholera, we need to understand how epidemics begin, how they spread, and how they decline and eventually end. This requires extensive sampling of epidemic disease over time, alongside the background of endemic disease that may exist concurrently with the epidemic. The unique circumstances surrounding the Argentinian cholera epidemic of 1992–1998 presented an opportunity to do this. Here, we use 490 Argentinian V. cholerae genome sequences to characterise the variation within, and between, epidemic and endemic V. cholerae . We show that, during the 1992–1998 cholera epidemic, the invariant epidemic clone co-existed alongside highly diverse members of the Vibrio cholerae species in Argentina, and we contrast the clonality of epidemic V. cholerae with the background diversity of local endemic bacteria. Our findings refine and add nuance to our genomic definitions of epidemic and endemic cholera, and are of direct relevance to controlling current and future cholera epidemics. Pandemic cholera was reintroduced to Argentina in 1992, leading to epidemic spread. Here, the authors use whole genome sequencing to show how, over 6 years, epidemic cholera was caused by invariant 7PET lineage Vibrio cholerae , against a background of sporadic disease caused by diverse local strains.
Epidemiologic and Genomic Surveillance of Vibrio cholerae and Effectiveness of Single-Dose Oral Cholera Vaccine, Democratic Republic of the Congo
We conducted 4 years of epidemiologic and genomic surveillance of single-dose effectiveness of a killed whole-cell oral cholera vaccine (kOCV) and Vibrio cholerae transmission in the Democratic Republic of the Congo. We enrolled 1,154 patients with diarrhea; 342 of those had culture-confirmed cholera. We performed whole-genome sequencing on clinical and water V. cholerae isolates from 200 patient households, which showed annual bimodal peaks of V. cholerae clade AFR10e infections. A large clonal cholera outbreak occurred 14 months after a kOCV campaign of >1 million doses, likely because of low (9%) vaccine coverage in informal settlements. Clinical and water isolates collected in the same household were closely related, suggesting person-to-person and water-to-person transmission. Single-dose kOCV vaccine effectiveness 24 months after vaccination was 59.8% (95% CI 19.7%-79.9%), suggesting modest single-dose kOCV protection. kOCV campaigns combined with water, sanitation, and hygiene programs should be used to reduce cholera in disease-endemic settings worldwide.
Multidrug-resistant Shigella flexneri outbreak affecting humans and non-human primates in New Mexico, USA
Shigellosis is a gastrointestinal infection caused by species of Shigella . A large outbreak of Shigella flexneri serotype 2a occurred in Albuquerque, New Mexico between May 2021 and November 2023 that involved humans and non-human primates (NHP) from a local zoo. We analyzed the genomes of 202 New Mexican isolates as well as 15 closely related isolates from other states, and four from NHP. The outbreak was initially detected within men who have sex with men but then predominantly affected people experiencing homelessness. Nearly 70% of cases were hospitalized and there was one human death. The outbreak extended into Albuquerque’s BioPark Zoo, causing high morbidity and six deaths in NHPs. All isolates were multidrug-resistant, including towards fluoroquinolones, a first line treatment option which led to treatment failures in human and NHP populations. We show the circulation of the same S. flexneri strain in humans and NHPs, causing fatalities in both populations. This study demonstrates the threat of antimicrobial resistant organisms to vulnerable human and NHP populations and emphasizes the value of genomic surveillance within a One Health framework. A large outbreak of shigellosis occurred in Albuquerque, New Mexico in 2021–2023 and affected non-human primates at a local zoo as well as humans. Here, the authors describe the outbreak investigation and demonstrate that cases in non-human primates were caused by the same strain of Shigella flexneri as those causing human cases.
Aeromonas in South Asia: genomic insights into an environmental pathogen and reservoir of antimicrobial resistance
Aeromonads are an ecologically versatile group of bacteria that cause infections in aquatic animals and are recognised as emerging human pathogens. Despite this, our understanding of Aeromonas diversity, especially the relationship between clinical and environmental strains, remains limited. Here, we present a genomic analysis of the Aeromonas genus, comprising 1853 genomes, and a detailed comparison of clinical and environmental strains from South Asia, including 996 newly sequenced genomes from Bangladesh and India. Phylogenetic analyses revealed that Aeromonas is a highly diverse genus, with no distinct clade separating clinical and environmental isolates. We identified 28 Aeromonas species and 905 novel sequence types, comprising 72.5% of the genomes. Notably, we show a high incidence of antimicrobial resistance (AMR) genes across all isolates, including against front and last-line antibiotics. Finally, we highlight frequent misidentification of Aeromonas as Vibrio cholerae , which is relevant to cholera-endemic regions where both genera co-exist and are associated with diarrhoeal disease. Our study underscores Aeromonas as an important environmental AMR reservoir and emerging multi-species pathogen capable of spilling over into human populations. The bacterial genus Aeromonas includes emerging human pathogens, often misidentified as Vibrio cholerae . Here, the authors analyse genomic sequences of over 1,800 Aeromonas isolates, showing that clinical and environmental strains do not display clear differences in drug resistance or disease-causing potential.
Using Culture and Whole Genome Sequencing to Assess Sterilization to Reduce Bacterial Contamination of Ventilator Heater Wires
Ventilator-associated events (VAEs), including ventilator-associated pneumonia (VAP), are important among hospitalized patients due to their high morbidity, mortality, and associated costs. These infections are frequently caused by multidrug-resistant ESKAPE pathogens (Enterococcus, Staphylococcus, Klebsiella, Acinetobacter, Pseudomonas, and Enterobacter), which are known for their antibiotic resistance. Heater wires used in mechanical ventilators regulate air humidity and temperature which prevents complications when the upper airway is bypassed. However, because these are in direct contact with the air supplied to patients, they can become sources of infection and reservoirs for antimicrobial-resistant organisms. At a hospital in New Mexico, we transitioned from using low-level disinfectant wipes to sterile processing for heater wires. The dry climate in New Mexico accelerates the evaporation of disinfectants, reducing their effectiveness by shortening their contact time. Additionally, achieving full surface coverage with disinfectant wipes is difficult, compromising sterilization effectiveness. To address these challenges, we implemented a protocol to send heater wire probes to sterile processing for sterilization. We evaluated the impact of this change by comparing the prescence of bacteria on the probes before and after sterilization. Swabs from heater wire prongs were cultured and sequenced using Oxford Nanopore Technology. Metagenomic sequencing and analysis was also performed. Before the new protocol, we swabbed 19 clean probes and 11 used probes. Bacterial DNA was detected on all clean probes and bacterial growth found on 42% of clean probe cultures. Of these, 63% were positive for ESKAPE pathogens, with five out of eight probes showing all ESKAPE species, and three probes lacking only Enterobacter. Additionally, all of the clean probe cultures were positive for Stenotrophomonas, another well known multi-drug resistant pathogen. After the autoclaving protocol was implemented, no bacterial growth was observed cultures (72 hours) of freshly sterilized probes. In conclusion, sterilization significantly improved the cleanliness of heater wires over use of disinfectant wipes. This improved sterilization protocol is expected to reduce the risk of infection transmission and the incidence of VAEs, thereby improving patient safety and outcomes.