Using secondary cases to characterize the severity of an emerging or re-emerging infection

The methods to ascertain cases of an emerging infectious disease are typically biased toward cases with more severe disease, which can bias the average infection-severity profile. Here, we conducted a systematic review to extract information on disease severity among index cases and secondary cases identified by contact tracing of index cases for COVID-19. We identified 38 studies to extract information on measures of clinical severity. The proportion of index cases with fever was 43% higher than for secondary cases. The proportion of symptomatic, hospitalized, and fatal illnesses among index cases were 12%, 126%, and 179% higher than for secondary cases, respectively. We developed a statistical model to utilize the severity difference, and estimate 55% of index cases were missed in Wuhan, China. Information on disease severity in secondary cases should be less susceptible to ascertainment bias and could inform estimates of disease severity and the proportion of missed index cases.

787. Clinical and Genomic Epidemiology of mcr-9 Containing Carbapenem-resistant Enterobacterales Isolates in Metropolitan Atlanta, 2012-2017

Background Colistin is a last-resort antibiotic for multidrug resistant gram-negative infections. Recently, a new allele of the mobile colistin resistance (mcr) gene family designated mcr-9, has been reported. However, its clinical and phenotypic significance remains unclear. Methods The Centers for Diseases Control and Prevention-funded Georgia Emerging Infections Program (EIP) performs population- and laboratory- based surveillance for CRE isolated from sterile sites or urine in metropolitan Atlanta, GA including standardized chart abstraction. We queried genomes of carbapenem-resistant Enterobacterales (CRE) for mcr-9 from a convenience sample of Georgia EIP clinical isolates between 2012-2017. Isolates underwent phenotypic characterization by broth microdilution and population analysis profiling. Nine available E. cloacae (two mcr-9 positive, seven mcr-9 negative) genomes from the National Institutes of Health were included in downstream genomic analysis. Fastq files underwent de novo assembly, annotation and AMR and virulence gene prediction, pan-genome association analysis, pairwise comparisons of average nucleotide identity and phylogenetic tree construction based on core genes. We compared characteristics and outcomes of mcr-9 positive and negative CRE cases. Results Among 449 sequenced CRE genomes, thirteen (2.9%) were found to harbor mcr-9, all of which were E. cloacae. Fourteen mcr-9 negative E. cloacae (n=14) were included as a comparative group. E. cloacae was most commonly isolated from the urine (22/24, 86%), and none were community associated. The median colistin MIC, rates of heteroresistance and inducible resistance were similar between mcr-9 positive and negative isolates (Table 1). 90-day mortality was high in both mcr-9 positive (31%) and negative (7% cases (p=0.28, Table 1). Phylogenetic analysis revealed no geo-temporal clustering (Figure 1). Plasmid-associated genes were significantly associated with the presence of mcr-9 (p< 0.001). Phylogeny and average nucleotide identity heatmap of mcr-9 positive and mcr-9 negative E. cloacae. Figure Legend 1: Phylogeny and average nucleotide identity heatmap of mcr-9 positive (n=13) and mcr-9 negative (n=14) E. cloacae from Georgia Emerging Infection program in addition to 9 available E. cloacae (two mcr-9 positive, seven mcr-9 negative) from the National Institutes of Health. A phylogenetic tree based on a core gene alignment containing 1,904 genes defined using Roary v3.13.0. was generated using IQtree v2.0.3. A maximum likelihood tree was generated by running 1,000 bootstrap replicates under the generalized time-reversible model of evolution. The tree was visualized and annotated using Interactive Tree of Life (iTOL) v4. Pairwise comparisons of average nucleotide identity on the assembled genomes were performed with the Mashmap method using fastANI v1.32. Abbreviations: GA EIP: Georgia Emerging Infection Program, NIH: National Institutes of Health, Table 1: Carbapenem-resistant E. cloacae clinical and microbiological characteristics Conclusion The presence of mcr-9 was not associated with significant changes in colistin resistance or clinical outcomes. Disclosures All Authors: No reported disclosures

Tularemia Goes West: Epidemiology of an Emerging Infection in Austria

The zoonotic disease tularemia is caused by the Gram-negative bacterium Francisella tularensis, with the two major subspecies tularensis and holarctica being responsible for infections in humans and animals. The F. tularensis subspecies holarctica is less virulent and prevalent in Europe and Asia. Over the last few centuries, few epidemic outbreaks and low numbers of infections have been registered in the eastern part of Austria, specifically in the provinces of Lower Austria, Burgenland, and Styria. The reported infections were mostly associated with hunting hares and the skinning of carcasses. Within the last decade, ticks have been identified as important vectors in Tyrol and served as first evidence for the spread of F. tularensis to Western Austria. In 2018, the pathogen was detected in hares in the provinces of Tyrol, Vorarlberg, and Salzburg. We presume that F. tularensis is now established in most regions of Austria, and that the investigation of potential host and vector animals should be spotlighted by public institutions. Tularemia in humans presents with various clinical manifestations. As glandular, ulceroglandular, and typhoidal forms occur in Austria, this infectious disease should be considered as a differential diagnosis of unknown fever.