NEW YORK – Global health agencies are calling for increased diagnostic capabilities to speedily combat a newly declared mpox public health emergency.
The World Health Organization, the Africa Centres for Disease Control and Prevention, and global diagnostics organization FIND say enhanced support for diagnostics — particularly point-of-care molecular tests — is required after the declaration last week of a global public health emergency caused by an mpox variant known as clade I.
"There is an urgent need for a coordinated response," said Emmanuel Agogo, director of pandemic threats at FIND.
In diagnostics, this includes collaborating and sharing knowledge at the community, country, and global level, Agogo said, as well as scaling up the manufacturing, procurement, and rollout of diagnostics once they are approved by regulators.
"The goal should be to ensure access to quality, well-performing tests for countries and communities that need them," Agogo said.
The need has also evolved somewhat since a prior global outbreak that was caused by mpox clade IIb.
"Different clades cause different outbreaks," Agogo explained, "So it’s important to be able to detect both."
The clade IIb mpox emergency that began in 2022 led to more than 92,000 cases globally, nearly one third of which occurred in the US. It also caused 208 deaths worldwide, 58 of which were in the US.
But unlike clade IIb, clade I mpox tends to cause a greater number of severe infections and have a higher mortality rate in endemic countries, the US Department of Health and Human Services said last week.
Between January 2023 and mid-April 2024, multiple clade I outbreaks centered in the Democratic Republic of Congo caused 19,919 cases of suspected clade I mpox, and 975 deaths, according the US Centers for Disease Control and Prevention, although clade I incidence rates in the US are projected to be lower should the virus ever begin circulating here.
The populations impacted by the two outbreaks are also different.
While the initial clade IIb outbreak spread globally primarily through sexual contact between men, the current clade I outbreak is being driven by female sex workers but is spreading mostly among children in Africa, according to the Africa CDC. This spread may occur through non-sexual skin-to-skin contact and potentially also via large respiratory droplets.
Specifically, through mid-April people younger than 15 made up roughly two thirds of suspected clade I cases and three quarters of suspected deaths; kids between 1 and 5 years old accounted for almost 30 percent of the clade I cases.
FIND recently expounded diagnostics-specific goals for the first 100 days of the new mpox emergency. Primary among these is accelerating the development and assessment of rapid molecular tests that are capable of detecting both clades I and II and that are also suitable for use in primary and community care.
Current testing landscape
Primary care testing allows patients to get same-day diagnostic results at a clinic or hospital using rapid or point-of-care assays.
While the FDA maintains a list of numerous lab-developed tests and issued templates for mpox diagnostic device Emergency Use Authorization — including one for antigen tests — the agency was previously prioritizing review of high-throughput molecular assays from experienced developers with high manufacturing capacity.
Currently there are four lab-based molecular diagnostic assays — from Abbott Laboratories, Diacarta, Quest Diagnostics, and Roche Molecular Systems — and one point-of-care diagnostic device — from Cepheid — that have obtained FDA EUA, according to the FIND test directory.
The FDA also granted EUAs to a test from CDC and to a home-collection kit from Laboratory Corporation of America, as well as EUAs to tests from Thermo Fisher Scientific and Becton Dickinson that have since been revoked at the companys' request. And, a 25-minute point-of-care mpox test from Cue Health was granted EUA last year, but Cue has since filed for bankruptcy and shuttered.
The only EUA point-of-care molecular test currently commercially available is the Xpert Mpox test from Cepheid, a Danaher company.
Jennifer Rakeman-Cagno, Cepheid's senior director of medical affairs and public health programs, said in an interview that the Xpert swab-based test takes 36 minutes, with an early termination for positive results.
It calls out two targets: clade II-specific mpox and NVOs in general. However, she noted, "in an outbreak, the non-variola orthopox result can be determined in the context of the local epidemiology as diagnostic for clade I."
Since the WHO declared the emergency last week, Rakeman-Cagno said Cepheid has been coordinating with its partners to get tests to where they are needed. "We've been working very hard to address the need for increased access to testing, and we are prioritizing orders as best we can to meet the outbreak response needs across the globe," she said.
Agogo also noted that other POC molecular tests are currently in development.
The Viral Vesicular test from Qiagen is a research-use only syndromic panel that detects seven targets, including mpox clades I and II, and strains of HSV and VZV.
Qiagen spokesperson Thomas Theuringer said that the firm has a range of products to support mpox testing, including sample preparation kits and automation, qPCR and digital PCR assays, dedicated QIAseq assays for targeted and shotgun sequencing, and curated mpox datasets for bioinformatic analysis.
The firm is working closely with public health institutions worldwide to respond to mpox, Thuringer said. "We will continue expanding our offerings in the coming weeks by introducing additional solutions specifically for mpox detection," he added, but noted that whether the firm will pursue EUA or the CE mark for mpox testing will depend on how the situation evolves.
The Standard M10 MPXV and Standard M10 MPX/OPX tests from SD Biosensor, meanwhile, are also point-of-care mpox tests.
Jiwon Lim, leader of the public relations team at SD Biosensor, said that both tests run on the firm's sample-to-answer system with results in under an hour. The MPXV test qualitatively detects the E9L gene and G2R gene of the virus in serum, plasma, whole blood, nasopharyngeal, or oropharyngeal swab samples using real-time PCR, Lim said, while the MPX/OPX test detects DNA from both mpox and orthopoxvirus in those same sample types as well as in skin lesion samples.
"SD Biosensor's mpox POC PCR tests have recently obtained export approval and are actively being supplied to various countries," Lim said.
Detecting both clades is key, yet of the 131 mpox assays currently listed in FINDs test directory, only three specify which clades they detect. On the other hand, while some tests detect NVOs, generally, in the context of an mpox outbreak a positive result for that target would be unlikely to represent camelpox or cowpox infections, for example.
Of the total number of mpox tests in FIND's database, 99 fit the category of molecular, nucleic acid amplification, or PCR tests, while 32 are immunoassays, and 18 are antigen tests. Additionally, 93 are lab-based assays, 25 are near point-of-care, and 13 are true point-of-care assays. And 84 of the mpox tests on FIND's site have obtained the CE-IVDD mark.
Still, FIND is now calling on developers to "ensure that their tests can broadly detect both virus clades," Agogo said.
Along these lines, Applied DNA Biosciences, for example, announced on Friday that it has submitted a validation package to the New York State Department of Health to expand its Linea Mpox Virus 1.0 Assay to include mpox Clade I.
Due to concerns about potential genomic deletions affecting test efficacy, the US CDC has also guided that an NVO test be used in addition to clade-specific testing, and that positive NVO or negative clade II test results be further investigated through sequence analysis.
Furthermore, "Multiplex tests for other similar diseases, such as chickenpox and herpes, are also useful," Agogo said, as these can cause skin lesions as well.
In this vein, the National Institutes of Health's Rapid Acceleration of Diagnostics (RADx) program issued a call for direct tests to detect and differentiate mpox, herpes simplex viruses types 1 and 2, Treponema pallidum, and varicella-zoster virus from swabs of skin lesions.
While few existing antigen tests have been clinically validated, "Molecular tests are more reliable in differentiating [mpox] viral clades," Agogo explained, adding that there is not as much information available on antigen test performance.
FIND has also supported test evaluations and hopes to launch a second round of evaluations in the next few months, Agogo said.
The FDA, meanwhile, will also continue reviewing mpox assays. The agency "plays a critical role in protecting the US from threats such as emerging infectious diseases, including the recent monkeypox outbreak," a spokesperson said in an email, and rapid detection of monkeypox cases requires wide availability of diagnostic testing to help control the spread of this contagious infection.
Last week, FDA also noted in a statement that the risk of clade I infection to the general public in the US remains "very low," adding that, "Due to efforts over the last nine months, the US is well prepared to rapidly detect, contain, and manage" any domestic clade I cases.
Similarly, the US CDC currently monitors wastewater for mpox with surprisingly high sensitivity, and the agency's current map shows very low, intermittent detection of clade II in the US.
Although there have been no clade I cases in the US so far, and no detection by wastewater in the US, as of yesterday there were confirmed cases in five African countries outside of the DRC, as well as in Sweden and Thailand.
In a statement on Thursday, the CDC said that the US "continues to increase the capacity to detect cases of clade I and clade IIb mpox through existing surveillance systems, including wastewater testing, and through expanding the robust diagnostic testing capacity built during the ongoing clade IIb outbreak to ensure coverage for clade I." The agency also added that, "The ability to expedite such diagnostic testing — in particular for those with recent travel to DRC or neighboring countries — also supports rapid detection."
The CDC also noted that since March 2024 it has worked with the US Agency for International Development to provide $20 million to support clade I mpox response efforts in Central and Eastern Africa. And, on Tuesday USAID announced up to an additional $35 million in emergency health assistance for the region, pending Congressional notification, that includes assistance with diagnostics.
FIND's Agogo also said a mechanism called surge funding may further help to accelerate development and equitable access to diagnostics.
"These are a range of funds," he explained, including top-ups from government donors like the Organisation for Economic Co-operation and Development that may also redirect funding from an Official Development Assistance government aid pool, as well as development banks, and some private foundation funding. And,surge funding can be distributed through international coordination platforms like the ACT-A program to help prioritize and allocate it where needed, he said.
While FIND's 100-day mission — which also calls for increasing access to biological samples and expanding access and manufacturing through harmonizing regulatory with procurement — expires in November, Agogo said improved speed of response will be enabled by learnings from the previous outbreak.
"We should aim high for any public health emergency to ensure rapid availability of medical countermeasures," he said.