Published on Tue Sep 28 2021

Discovering disease-causing pathogens in resource-scarce Southeast Asia using a global metagenomic pathogen monitoring system

Bohl, J. A., Lay, S., Chea, S., Ahyong, V., Parker, D. M., Gallagher, S., Fintzi, J., Man, S., Ponce, A., Sreng, S., Kong, D., Oliveira, F., Kalantar, K., Tan, M., Fahsbender, L., She, J., Neff, N., Detweiler, A., Ly, S., Sath, R., Rekol, H., Lon, C., Tato, C. M., DeRisi, J., Manning, J. M., Huch, C., Leang, R., Kry, H.

Using unbiased metagenomic next generation sequencing (mNGS), we identified a variety of vector-borne, zoonotic and emerging pathogens responsible for undifferentiated fevers in Cambodia. Early detection of chikungunya virus presaged a larger national outbreak of more than 6,000 cases.

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Abstract

Understanding the regional pathogen landscape and surveillance of emerging pathogens is key to mitigating epidemics. Challenges lie in resource-scarce settings, where outbreaks are likely to emerge, but where laboratory diagnostics and bioinformatics capacity are limited. Using unbiased metagenomic next generation sequencing (mNGS), we identified a variety of vector-borne, zoonotic and emerging pathogens responsible for undifferentiated fevers in a peri-urban population in Cambodia. From March 2019 to October 2020, we enrolled 473 febrile patients aged 6 months to 65 years of age presenting to a large peri-urban hospital in Cambodia. We collected sera and prepared sequencing libraries from extracted pathogen RNA for unbiased metagenomic sequencing and subsequent bioinformatic analysis on the global cloud-based platform, IDseq. We employed multivariate Bayesian models to evaluate specific pathogen risk causing undifferentiated febrile illness. mNGS identified vector-borne pathogens as the largest clinical category with dengue virus (124/489) as the most abundant pathogen. Underappreciated zoonotic pathogens such as Plasmodium knowlesi, leptospirosis, and co-infecting HIV were also detected. Early detection of chikungunya virus presaged a larger national outbreak of more than 6,000 cases. Pathogen-agnostic mNGS investigation of febrile persons in resource-scarce Southeast Asia is feasible and revealing of a diverse pathogen landscape. Coordinated and ongoing unbiased mNGS pathogen surveillance can better identify the breadth of endemic, zoonotic or emerging pathogens and deployment of rapid public health response.