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Monkeypox virus (MPXV) is a reemerging virus of global concern. An outbreak of clade I MPXV affected 20 captive chimpanzees in Cameroon in 2016. We describe the epidemiology, virology, phylogenetics, and clinical progression of this outbreak. Clinical signs included exanthema, facial swelling, perilaryngeal swelling, and eschar. Mpox can be lethal in captive chimpanzees, with death likely resulting from respiratory complications. We advise avoiding anesthesia in animals with respiratory signs to reduce the likelihood of death. This outbreak presented a risk to animal care staff. There is a need for increased awareness and a One Health approach to preparation for outbreaks in wildlife rescue centers in primate range states where MPXV occurs. Control measures should include quarantining affected animals, limiting human contacts, surveillance of humans and animals, use of personal protective equipment, and regular decontamination of enclosures., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The surveillance and identification of emerging, reemerging, and unknown infectious disease pathogens is essential to national public health preparedness and relies on fluidity, coordination, and interconnectivity between public and private pathogen surveillance systems and networks. Developing a national sentinel surveillance network with existing resources and infrastructure could increase efficiency, accelerate the identification of emerging public health threats, and support coordinated intervention strategies that reduce morbidity and mortality. However, implementing and sustaining programs to detect emerging and reemerging pathogens in humans using advanced molecular methods, such as metagenomic sequencing, requires making large investments in testing equipment and developing networks of clinicians, laboratory scientists, and bioinformaticians. In this study, we sought to gain an understanding of how federal government agencies currently support such pathogen agnostic testing of human specimens in the United States. We conducted a landscape analysis of federal agency websites for publicly accessible information on the availability and type of pathogen agnostic testing and details on flow of clinical specimens and data. The website analysis was supplemented by an expert review of results with representatives from the federal agencies. Operating divisions within the US Department of Health and Human Services and the US Department of Veterans Affairs have developed and sustained extensive clinical and research networks to obtain patient specimens and perform metagenomic sequencing. Metagenomic facilities supported by US agencies were not equally geographically distributed across the United States. Although many entities have work dedicated to metagenomics and/or support emerging infectious disease surveillance specimen collection, there was minimal formal collaboration across agencies.

To better identify emerging or reemerging pathogens in patients with difficult-to-diagnose infections, it is important to improve access to advanced molecular testing methods. This is particularly relevant for cases where conventional microbiologic testing has been unable to detect the pathogen and the patient's specimens test negative. To assess the availability and utility of such testing for human clinical specimens, a literature review of published biomedical literature was conducted. From a corpus of more than 4,000 articles, a set of 34 reports was reviewed in detail for data on where the testing was being performed, types of clinical specimens tested, pathogen agnostic techniques and methods used, and results in terms of potential pathogens identified. This review assessed the frequency of advanced molecular testing, such as metagenomic next generation sequencing that has been applied to clinical specimens for supporting clinicians in caring for difficult-to-diagnose patients. Specimen types tested were from cerebrospinal fluid, respiratory secretions, and other body tissues and fluids. Publications included case reports and series, and there were several that involved clinical trials, surveillance studies, research programs, or outbreak situations. Testing identified both known human pathogens (sometimes in new sites) and previously unknown human pathogens. During this review, there were no apparent coordinated efforts identified to develop regional or national reports on emerging or reemerging pathogens. Therefore, development of a coordinated sentinel surveillance system that applies advanced molecular methods to clinical specimens which are negative by conventional microbiological diagnostic testing would provide a foundation for systematic characterization of emerging and underdiagnosed pathogens and contribute to national biodefense strategy goals.