728. Genomic Characterization of Burkholderia pseudomallei Isolates in Colombia

Abstract Background Melioidosis is a serious infection caused by Burkholderia pseudomallei (Bps), an opportunistic organism, highly adaptable and with a wide array of intrinsic virulence factors and antimicrobial resistance determinants. Bps is underdiagnosed due to its slow growth on routine laboratory media and the lack of robust diagnostic infrastructure in rural areas of low/middle income countries. Recent data indicates that Bps infections are increasing in Colombia (COL). However, the understanding of the genomic epidemiology and population structure of the emerging Bps isolates in COL is unknown. Here we characterize the genomic features of Bps isolates from infected patients in COL. Methods We identified 13 Bps clinical isolates recovered in 5 Colombian cities between 2018 and 2020. We performed WGS and phylogenomic analyses using Bayesian methods. For comparisons, we included 82 publicly available genomes from Bps recovered worldwide (including 10 additional isolates from COL). Additionally, we characterized the resistome, virulome and MLST of all isolates. Results 12 out of the 13 isolates were confirmed as Bps and 1 belonged to the B. cepacia complex. The Bps population structure was divided in two main clades: clade 1 with isolates from Asia and Australia, and clade 2 with isolates from Africa, America, and the Caribbean (Figure 1). We found two groups of Colombian isolates, the first was related to ST518 and the second, highly diverse including 11 different STs (1742, 1748, 92, among others). Genomic characterization showed the presence of β-lactamases PenA (n=11) and OXA-57 (n=1). We also identified a T584A substitution in PBP3 (n=11). All genomes contained virulence determinants of motility (BimA), invasion (Flagella), signaling (CdpA) and adherence (Type IV pili). Type III and VI secretion systems, were also found in all isolates resembling Bps from other parts of the world. Figure 1. Maximum clade credibility tree of 82 genomes of Bps. The inner ring shows the ST for each genome, while the outer ring shows the geographical region associated with them. Groups highlighted in red show the location of the Colombian genomes and those related to them. Conclusion Bps is an emerging pathogen in COL and its population structure seems highly diverse, predominantly of the American lineage and absence of Australasians strains. A high prevalence ( >90%) of resistance determinants, particularly related to β-lactams, suggest that active surveillance of these emergent pathogens is needed in countries like COL. Disclosures Cesar A. Arias, M.D., MSc, Ph.D., FIDSA, Entasis Therapeutics (Grant/Research Support)MeMed Diagnostics (Grant/Research Support)Merk (Grant/Research Support) Lorena Diaz, PhD , Nothing to disclose


Session: P-35. Global Health
Background. Melioidosis is a serious infection caused by Burkholderia pseudomallei (Bps), an opportunistic organism, highly adaptable and with a wide array of intrinsic virulence factors and antimicrobial resistance determinants. Bps is underdiagnosed due to its slow growth on routine laboratory media and the lack of robust diagnostic infrastructure in rural areas of low/middle income countries. Recent data indicates that Bps infections are increasing in Colombia (COL). However, the understanding of the genomic epidemiology and population structure of the emerging Bps isolates in COL is unknown. Here we characterize the genomic features of Bps isolates from infected patients in COL.
Methods. We identified 13 Bps clinical isolates recovered in 5 Colombian cities between 2018 and 2020. We performed WGS and phylogenomic analyses using Bayesian methods. For comparisons, we included 82 publicly available genomes from Bps recovered worldwide (including 10 additional isolates from COL). Additionally, we characterized the resistome, virulome and MLST of all isolates.
Results. 12 out of the 13 isolates were confirmed as Bps and 1 belonged to the B. cepacia complex. The Bps population structure was divided in two main clades: clade 1 with isolates from Asia and Australia, and clade 2 with isolates from Africa, America, and the Caribbean (Figure 1). We found two groups of Colombian isolates, the first was related to ST518 and the second, highly diverse including 11 different STs (1742, 1748, 92, among others). Genomic characterization showed the presence of β-lactamases PenA (n=11) and OXA-57 (n=1). We also identified a T584A substitution in PBP3 (n=11). All genomes contained virulence determinants of motility (BimA), invasion (Flagella), signaling (CdpA) and adherence (Type IV pili). Type III and VI secretion systems, were also found in all isolates resembling Bps from other parts of the world. Conclusion. Bps is an emerging pathogen in COL and its population structure seems highly diverse, predominantly of the American lineage and absence of Australasians strains. A high prevalence ( >90%) of resistance determinants, particularly related to β-lactams, suggest that active surveillance of these emergent pathogens is needed in countries like COL. Background. Hearing loss (HL) is the second leading cause of disability affecting approximately 19% of the world's population. Despite well known social, economic, and neurologic consequences this condition receives little attention. Lassa Fever (LF) was noted to be associated with HL shortly after its discovery in the 1970's. However, the true burden of this sequelae is likely underestimated due to a lack of standardized measurement and reporting.
Methods. We performed a cross-sectional study of LF survivors and household controls in Kenema, Sierra Leone. Upon recruitment, survivors and controls were screened for HL by determining Pure Tone Averages (PTA) of air conduction thresholds using an AMBCO audiometer, according to WHO standards. Individuals found to have elevated PTAs were referred to confirmatory testing measuring both air and bone thresholds using a SHOEBOX audiometer to differentiate sensorineural and conductive HL. All subjects completed symptom questionnaires and physical exams to understand the full spectrum of viral sequelae.
Results. 94 LF survivors and 281 controls were recruited. The average age of LF survivors was higher than controls (32.9 vs 28.7, p=0.008). Of these 94 LF survivors, 40 (43%) were found to have HL in comparison to 40 (14%) of controls (p< 0.001). Lassa fever survivors were also found to have significantly worse HL with 16 (40%) found to have profound HL compared to only 2 (5%) of controls (p< 0.001). Logistic regression of this cohort found that LF infection (OR = 1.30, p< 0.001), any inner or middle ear symptoms (OR = 1.20, p=0.041), or pharyngeal symptoms (OR = 1.23, p=0.012) were significant risk factors of developing HL (p< 0.001). Interestingly the development of any pulmonary symptoms was protective of HL (OR = 0.86, p=0.039). Animal model studies suggested that LF infection may result in the development of an ANCA