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Host-response Transcriptional Biomarkers Accurately Discriminate Bacterial and Viral Infections of Global Relevance

Article scientifique 2023 Anglais

Résumé

Abstract Limited diagnostics challenge management of acute febrile illness and sepsis (AFI/sepsis) globally. We generated transcriptomes for a 294-participant (USA, Sri Lanka) discovery cohort with AFI/sepsis. We used lasso to derive gene expression classifiers followed by cross-validation and generated: 1) a single model to distinguish bacterial vs. viral (Global Fever-Bacterial/Viral [GF-B/V]) and 2) a two-model system to discriminate bacterial and viral in the context of noninfection (Global Fever-Bacterial/Viral/Non-infectious [GF-B/V/N]). We then translated to a multiplex RT-PCR assay and independent validation involved 101 participants (USA, Sri Lanka, Australia, Cambodia, Tanzania). The sensitivity of the GF-B/V model in the discovery cohort was 84.2% and specificity 94.7%. Validation in an independent cohort showed the GF-B/V model had sensitivity of 78.8% and specificity of 84.3%. Similarly, the discovery cohort performance characteristics for bacterial infection for the GF-B/V/N model were was 87.7% sensitivity and 84.2% specificity, respectively. For viral infection, the sensitivity was 83.7% and specificity 81.5%. In independent validation, the sensitivity and specificity were 82.7% and 80.4%, respectively, for bacterial infection and 76.5% and 80.8%, respectively, for viral infection. Performance did not vary with age, demographics, or site. Host transcriptional response diagnostics distinguish bacterial and viral illness across global sites with different endemic pathogens.

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Ko, E., Reller, M., Tillekeratne, L., Bodinayake, C., Miller, C., Burke, T., Henao, R., McClain, M., Suchindran, S., Nicholson, B., Blatt, A., Petzold, E., Tsalik, E., Nagahawatte, A., Devasiri, V., Rubach, M., Maro, V., Lwezuala, B., Kodikara-Arachichi, W., Kurukulasooriya, R., Silva, A., Clark, D., Schully, K., Madut, D., Dumler, J., Kato, C., Galloway, R., Crump, J., Ginsburg, G., Minogue, T., Woods, C. (2023). Host-response Transcriptional Biomarkers Accurately Discriminate Bacterial and Viral Infections of Global Relevance. https://doi.org/10.21203/rs.3.rs-2419595/v1

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Auteur(s)

Emily R. Ko Megan E. Reller L. Gayani Tillekeratne Champica K. Bodinayake Cameron Miller Thomas W. Burke Ricardo Henao Micah T. McClain Sunil Suchindran Bradly P. Nicholson Adam Blatt Elizabeth Petzold Ephraim L. Tsalik Ajith Nagahawatte Vasantha Devasiri Matthew P. Rubach Venance P. Maro Bingileki F. Lwezuala Wasantha Kodikara-Arachichi Ruvini Kurukulasooriya Aruna D. Silva Danielle V. Clark Kevin L. Schully Deng B. Madut J. Stephen Dumler Cecilia Y. Kato Renee L. Galloway John A. Crump Geoffrey S. Ginsburg Timothy D. Minogue Christopher W. Woods

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