Matthew Clark | PubMed Health

PubMed2026

Incidence of invasive group A streptococcal infections and comparison of emm types from invasive infections, pharyngitis, and throat carriage in American Indian communities in the Southwest United States.

BACKGROUND: American Indian/Alaska Native (AI/AN) communities in the US have high rates of group A streptococcal (GAS) infections. We determined the incidence of invasive infections in AI communities in the Southwest and compared emm types from invasive infections, pharyngitis, and throat carriage. METHODS: Activities conducted in the White Mountain Apache Tribal lands (WMA) and Navajo Nation (NN) included active, laboratory-based surveillance for invasive GAS infections (WMA: 2019─2024; NN: 2023─2024; all ages); surveillance for GAS pharyngitis (2023-2024; children 0─17 years); and culture for GAS from oropharyngeal carriage samples (2019 and 2022─2023; children 0─14 years). Emm types were determined by whole-genome sequencing. Annual incidence rates were calculated using Poisson regression. RESULTS: In WMA, age-standardized rates of invasive infections ranged from 80-270/100,000 persons between 2019-2024. Predominant emm types varied (n=74 isolates): 91 (59%) and 49 (32%) in 2019-2020, and 43 (40%) and 53 (30%) in 2023. In NN, rates were 40-60/100,000 persons in 2023-2024; common emm types (n=51) were 53 (28%), 101 (18%), and 12 (16%). In WMA and NN, emm types 1, 12, and 53 predominated in pharyngitis (n=190), and 1, 12, and 91 in throat carriage (n=119). CONCLUSIONS: Rates of invasive GAS infections in these communities were 3-35 times higher than the national US average (12.2/100,000 in 2024). Emm types varied over time with limited overlap in strains from throat carriage or pharyngitis isolates and those from invasive infections. Findings support continuing GAS surveillance and engaging AI/AN communities throughout vaccine development and evaluation.

Indigenous health↗

PubMed2022

A Multitrait Locus Regulates Sarbecovirus Pathogenesis.

Infectious diseases have shaped the human population genetic structure, and genetic variation influences the susceptibility to many viral diseases. However, a variety of challenges have made the implementation of traditional human Genome-wide Association Studies (GWAS) approaches to study these infectious outcomes challenging. In contrast, mouse models of infectious diseases provide an experimental control and precision, which facilitates analyses and mechanistic studies of the role of genetic variation on infection. Here we use a genetic mapping cross between two distinct Collaborative Cross mouse strains with respect to severe acute respiratory syndrome coronavirus (SARS-CoV) disease outcomes. We find several loci control differential disease outcome for a variety of traits in the context of SARS-CoV infection. Importantly, we identify a locus on mouse chromosome 9 that shows conserved synteny with a human GWAS locus for SARS-CoV-2 severe disease. We follow-up and confirm a role for this locus, and identify two candidate genes, CCR9 and CXCR6, that both play a key role in regulating the severity of SARS-CoV, SARS-CoV-2, and a distantly related bat sarbecovirus disease outcomes. As such we provide a template for using experimental mouse crosses to identify and characterize multitrait loci that regulate pathogenic infectious outcomes across species. IMPORTANCE Host genetic variation is an important determinant that predicts disease outcomes following infection. In the setting of highly pathogenic coronavirus infections genetic determinants underlying host susceptibility and mortality remain unclear. To elucidate the role of host genetic variation on sarbecovirus pathogenesis and disease outcomes, we utilized the Collaborative Cross (CC) mouse genetic reference population as a model to identify susceptibility alleles to SARS-CoV and SARS-CoV-2 infections. Our findings reveal that a multitrait loci found in chromosome 9 is an important regulator of sarbecovirus pathogenesis in mice. Within this locus, we identified and validated CCR9 and CXCR6 as important regulators of host disease outcomes. Specifically, both CCR9 and CXCR6 are protective against severe SARS-CoV, SARS-CoV-2, and SARS-related HKU3 virus disease in mice. This chromosome 9 multitrait locus may be important to help identify genes that regulate coronavirus disease outcomes in humans.

Animals↗