期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2022
卷号：119
期号：11
DOI：10.1073/pnas.2115285119
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance
Metagenomic pathogen sequencing offers an unbiased approach to characterizing febrile illness. In resource-scarce settings with high biodiversity, it is critical to identify disease-causing pathogens in order to understand burden and to prioritize efforts for control. Here, metagenomic next-generation sequencing (mNGS) characterization of the pathogen landscape in Cambodia revealed diverse vector-borne and zoonotic pathogens irrespective of age and gender as risk factors. Identification of key pathogens led to changes in national program surveillance. This study is a “real world” example of the use of mNGS surveillance of febrile individuals, executed in-country, to identify outbreaks of vector-borne, zoonotic, and other emerging pathogens in a resource-scarce setting.
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 metagenomic next-generation sequencing (mNGS), we identified a variety of vector-borne, zoonotic, and emerging pathogens responsible for undifferentiated fevers in a periurban population in Cambodia. From March 2019 to October 2020, we enrolled 464 febrile patients (and 23 afebrile persons) aged 6 mo to 65 y presenting to a large periurban 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, CZID (“IDseq”). We employed multivariable regression models to evaluate pathogen risk factors associated with undifferentiated febrile illness. mNGS identified vector-borne pathogens as the largest clinical category with dengue virus (124 of 489) as the most abundant pathogen. Underappreciated zoonotic pathogens, such as
Plasmodium knowlesi, leptospirosis, and coinfecting 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 mNGS pathogen surveillance can better identify the breadth of endemic, zoonotic, or emerging pathogens and deployment of rapid public health response.
