Clinical labs learned about the limitations of mpox testing during last summer’s outbreak. However, they also took away valuable lessons to prepare for the next emerging disease.
By Erica Frew
When the latest outbreak of mpox also known as monkeypox emerged in May 2022, it was not limited to the regions of Africa where the disease is endemic. Instead, mpox spread rapidly around the world. In May there were about 200 confirmed cases worldwide; by December that number surged to more than 82,000 people in more than 100 countries.1,2
While those numbers give us a sense of the global impact of the mpox outbreak, they fail to represent what happened in the clinical laboratory community. Labs that were already stretched thin due to COVID-19 testing struggled to obtain the supplies needed for mpox testing. In the U.S., testing capabilities were extremely limited. Consider New York City, an epicenter of the mpox outbreak. With a population greater than 8 million, just 10 people could be tested for mpox on any given day from May until July.3 With such a severe testing bottleneck—driven largely by an inability to access reference materials and other needed assay components—the confirmed number of infected individuals is likely a significant undercount of the actual mpox cases during that phase of the outbreak.
In mid-July, the U.S. Centers for Disease Control and Prevention (CDC) partnered with five commercial laboratories to increase the nation’s testing capacity to 70,000 tests per week, compared to the previous limit of 6,000 tests per week.4
While challenges associated with mpox testing were in some ways unique to this particular outbreak, in a broader sense, they reveal ongoing difficulties faced by clinical laboratories. The need to develop, validate, and scale up new tests quickly, especially when existing bandwidth is largely consumed by other testing demands, is a major burden for clinical labs.
For mpox, testing constraints were eased when the U.S. Food & Drug Administration was empowered in September to issue emergency use authorization (EUA) for new assays. With corporate diagnostic developers now given a pathway to commercialize tests for use in clinical labs, they will have alternatives to develop their own tests. As of early December 2022, two manufacturers had been granted EUA for their mpox assays, and at least two other companies had released synthetic molecular controls to ease supply bottlenecks for reference materials.
A deeper look at mpox testing offers a number of lessons the clinical lab community and the diagnostic industry can take to try to improve the ability to respond to emerging public health threats.
The first cases of this latest mpox outbreak were confirmed in London in early May 2022, and were linked to an individual who had recently traveled to Nigeria.5 Within a couple of weeks, additional cases had been detected that confirmed community spread in the U.K. From there, mpox spread quickly throughout Europe and then to North America, South America, and Asia. By late July, the World Health Organization (WHO) had declared a public health emergency, stopping short of officially declaring a pandemic.
As of early December 2022, the hardest-hit countries were the U.S. with nearly 30,000 cases; Brazil with more than 10,000 cases; Spain with almost 7,500 cases; and France with more than 4,000 cases. Colombia, the U.K., Germany, Peru, and Mexico each had more than 3,000 cases.2
Mpox Testing Constraints
To find ways to better react to similar outbreaks in the future, it is worth reviewing the challenges faced by clinical labs in ramping up mpox testing capabilities. As expected with an outbreak of a disease never before seen by most of these laboratories, many of those limitations emerged from a lack of relevant information and assay supplies.
For example, even today the sequences and assay protocols recommended for mpox testing are not specific to the virus, but rather are for the genus of non-variola Orthopoxvirus DNA viruses to which mpox belongs.6,7 This shortcut was considered acceptable, because there were no other widely circulating members of the genus during the mpox outbreak. In a different situation, such broad testing could have led to a number of false positives and confounding results. Clearly, the approval and availability of disease-specific sequences and protocols should be prioritized during outbreaks of novel or emerging diseases to ensure that test results are as specific and useful as possible for tracking both individual and public health.
In what has probably been the biggest driver of mpox testing limitations, access to necessary assay components, including reliable controls and reference materials, has been quite restricted for much of the outbreak period. Developing, validating, and utilizing new tests in response to an outbreak such as mpox — unfamiliar to most clinical laboratories — is often dependent on the ability to use confirmed positive samples as controls.
That is a huge access hurdle that prevents most laboratories from being able to stand up testing early in an outbreak. Synthetic molecular controls offer a more reliable and accessible alternative, but it takes time for commercial manufacturers to develop and produce them. Establishing incentives for companies to develop these materials quickly would be one way to fast-track the availability of high-quality synthetic controls. These materials would then allow more laboratories to develop their own tests to increase global testing capacity.
Looking to the Next Outbreak
Infectious disease experts have been sounding the alarm for years, warning that spillover events bringing zoonotic pathogens into the human population are set to increase. With contributing factors such as climate change, the reduction of wild animal habitats, and increased human interaction with wild animals, this trend in outbreaks of novel zoonotic diseases is likely to accelerate in the decades to come. It has never been so critical to plan for better strategies that will allow the clinical lab community to respond more quickly to future outbreaks.
The mpox outbreak highlighted the value of partnerships across government agencies, clinical laboratories, and commercial diagnostic companies. Using approaches such as emergency use authorizations as early as possible empowers companies to develop needed tests and assay materials and get them to the clinical lab market more quickly.
Other creative strategies that allow companies, labs, and government agencies to team up and fast-track testing products would be beneficial as well. For example, it’s easier to activate existing relationships than to create new ones in a crisis—diagnostic companies could find ways to establish partnerships with clinical labs that would make it easier for all parties to come together when needed to ramp up new testing capabilities. Careful strategic planning now could ensure a more effective response to the next outbreak.
ABOUT THE AUTHOR
Erica Frew is a product manager at Asuragen, a Bio-Techne brand, where she specializes in molecular controls for clinical tests.
- 2022 Monkeypox Outbreak: Global Trends. World Health Organization. https://worldhealthorg.shinyapps.io/mpx_global/. Accessed December 15, 2022.
- Mpox Data Explorer. Our World in Data. https://ourworldindata.org/explorers/monkeypox. Accessed December 15, 2022.
- Otterman S. “Monkeypox Vaccine Rollout Is Marred by Glitches in New York.” New York Times. July 7, 2022. https://www.nytimes.com/2022/07/07/nyregion/monkeypox-vaccine-rollout.html
- “HHS orders additional vaccine, increases testing capacity to respond to monkeypox outbreak.” ASPR Press Office. July 15, 2022. https://www.hhs.gov/about/news/2022/07/15/hhs-orders-additional-vaccine-increases-testing-capacity-to-respond-to-monkeypox-outbreak.html
- “Monkeypox cases confirmed in England – latest updates.” UK Health Security Agency. https://www.gov.uk/government/news/monkeypox-cases-confirmed-in-england-latest-updates. Last updated September 6, 2022. Accessed December 15, 2022.
- Monkeypox Emergency Use Authorizations for Medical Devices. U.S. Food & Drug Administration. https://www.fda.gov/medical-devices/emergency-use-authorizations-medical-devices/monkeypox-emergency-use-authorizations-medical-devices. Accessed December 15, 2022.
- 2022 Outbreak Cases and Data. U.S. Centers for Disease Control and Prevention. https://www.cdc.gov/poxvirus/monkeypox/response/2022/index.html. Accessed December 15, 2022.