Coordinating at-home testing for monkeypox may provide opportunities for clinical laboratories to add value for their physician clients
Microbiologists and clinical laboratory managers who oversee medical laboratory tests for monkeypox (aka, mpox) will be interested to learn that, according to the US Centers of Disease Control (CDC), cases per day have dropped into the single digits.
The United States led the world in cases during the 2022-2023 outbreak, according to the most recent CDC statistics. As of February 15, the US has reported 30,193 cases of monkeypox with 32 deaths.
Nevertheless, January 31 was the day that the US public health emergency involving monkeypox officially expired. Data from the World Health Organization shows the number of daily monkeypox cases in most countries around the world is declining, although numbers of cases are still increasing in some South American countries.
The global monkeypox outbreak appears to have slowed considerably, but are we out of the woods?
“There were concerns that there would be ongoing transmission and that ongoing transmission would become endemic in the United States like other STIs: gonorrhea, chlamydia, syphilis. We have not seen that occur,” Jonathan Mermin, MD (above), Director of the National Center for HIV, Viral Hepatitis, STD, and TB Prevention at the CDC, told CNN.”We are now seeing three to four cases a day in the United States, and it continues to decline. And we see the possibility of getting to zero as real.” This decline in monkeypox test corresponds with a similar decline in COVID-19 clinical laboratory testing as well. (Photo Copyright: CDC.)
Untried Vaccine and At-home Testing for Monkeypox
When the monkeypox outbreak began in May of 2022, there were concerns about the US’ level of preparedness for dealing with a second pandemic while also battling COVID-19. But monkeypox was not entirely unknown to the scientific and medical communities.
Monkeypox first appeared in 1958 amongst a colony of monkeys being kept for research. The origin of the disease is not known. According to the CDC, the first reported human case of monkeypox was in 1970. Prior to the 2022 outbreak, most cases were found in central and western African countries. Cases outside of those areas could be traced back to travel from those specific countries.
When cases of monkeypox first appeared in the US, public health officials were concerned about the availability of testing, vaccines, and treatments. As CNN reported, though there was a new vaccine available, its effectiveness against monkeypox had never been tested on humans.
That treatment, known as TPOXX (Tecovirimat), was an antiviral drug approved by the FDA in 2018 to treat smallpox in adults and children, according to an FDA factsheet. The drug was difficult to obtain, and it took until August of 2022 for the federal government to declare monkeypox a public health emergency. That allowed it to deploy emergency funds towards fighting the outbreak.
The demographic found to be at the highest risk of monkeypox infection were men who have sex with other men. According to MedPage Today, “Daskalakis had both pandemic experience as former senior lead on equity in COVID-19 data and engagement for the New York City Department of Health and Mental Hygiene and an ‘in’ with the LGBTQ+ community from his work in HIV prevention and his transparency about being a gay man.”
When comparing monkeypox to HIV, Daskalakis said, “This one [monkeypox], you don’t have to change behaviors for generations; it’s for a few months. Once you build your force field of immunity with vaccines, people can make their own informed decisions about their risk.”
Opportunities for Clinical Laboratories
So, how should clinical laboratories respond if there’s another monkeypox flare up?
Daskalakis advocates for home testing. “People that are going to order home tests are going to be motivated to action in other ways. And so, thinking about HIV home testing, which was the grandparent of COVID-19 home testing, this really shows us how you reach people you’re not going to reach when you have lab-based, provider-only testing … When you look at the HIV home testing data from the CDC, 26% of the people that ordered a home test had never been tested before. That is way higher than what you would expect,” he told MedPage Today.
We are not out of the woods in regard to monkeypox, vigilance is still required. But with existing harm reduction measures in the most vulnerable community, at-home testing and advancements in vaccines could help us keep our numbers as low as possible.
Experts cite high vaccination rates and behavioral changes among at-risk groups, but warn about complacency; clinical laboratories should remain vigilant
In July, Scott Gottlieb, MD, Commissioner of the US Food and Drug Administration (FDA) from May 2017 to April 2019, wrote an op-ed in The New York Times titled, “Monkeypox Is About to Become the Next Public Health Failure.” In it, he wrote, “Our country’s response to monkeypox has been plagued by the same shortcomings we had with COVID-19.” But has it improved? Clinical laboratory leaders and pathology group managers will find it informative to find out what has taken place since Gottlieb made his stark prediction.
The global monkeypox outbreak that emerged last spring appears to have subsided in the US and Europe, though it remains to be seen if the disease can be completely eradicated, according to multiple media reports. As of Oct. 26, 2022, the Centers for Disease Control and Prevention (CDC) reported a 7-day rolling average of 30 cases per day in the US, down from a peak of nearly 440/day in early August.
Cases are also down in cities that earlier reported heavy outbreaks. For example, the New York City Health Department reported a 7-day average of just two cases per day on Oct. 25, compared with 73/day on July 30.
And the San Francisco Department of Public Health announced on Oct. 20 that it would end the city’s public health emergency on monkeypox (MPX) effective on Oct. 31. “MPX cases have slowed to less than one case per day and more than 27,000 San Franciscans are now vaccinated against the virus,” the agency stated in a press release.
“Once again, we caution that a declining outbreak can be the most dangerous outbreak, because it can tempt us to think that the crisis is over and to let down our guard,” said World Health Organization (WHO) Director-General Tedros Adhanom Ghebreyesus, PhD, in an Oct. 12 global press briefing. “That’s not what WHO is doing. We are continuing to work with countries around the world to increase their testing capacity, and to monitor trends in the outbreak.” Clinical laboratories should not assume the outbreak has passed but continue to be vigilant and prepared for increased demand in monkeypox testing. (Photo copyright: ITU Pictures.)
Changing Behavior Lowers Infection Rates
In addition to high vaccination rates, public health experts have attributed the decline to behavioral changes among at-risk groups. “There were really substantial changes among men who have sex [with] men,” infectious disease physician Shira Doron, MD, of Tufts Medical Center in Boston, told ABC News.
On September 2, the CDC published the results of a survey indicating that about half of men who have sex with men “reported reducing their number of sex partners, one-time sexual encounters, and use of dating apps because of the monkeypox outbreak.”
Another likely factor is the disease’s limited transmissibility. “Initially, there was a lot of concern that monkeypox could spread widely at daycares or in schools, but, overall, there has been very little spread among children,” NPR reported.
But citing multiple studies, the NPR story noted “that often there isn’t very much virus in the upper respiratory tract,” where it might spread through talking or coughing. “Instead, the highest levels of virus occur on sores found on the skin and inside the anus.”
These studies, along with earlier research, “explain why monkeypox is spreading almost exclusively through contact during sex, especially anal and oral sex, during the current outbreak,” NPR reported.
Monkeypox Could Mutate, experts say
Despite the promising numbers, public health experts are warning that monkeypox could remain as a long-term threat to public health. According to an article in Nature, “At best, the outbreak might fizzle out over the next few months or years. At worst, the virus could become endemic outside Africa by reaching new animal reservoirs, making it nearly impossible to eradicate.”
In addition to the limited transmissibility of the virus, Nature noted that the outbreak stems from a relatively mild form of the pathogen and is rarely fatal. As of Oct. 28, the CDC reported a total of just six confirmed deaths in the US out of a total of 28,302 confirmed cases since the first infections were reported in May.
It is possible that the virus could mutate into a more contagious form, but Nature noted that monkeypox is a DNA virus, and that they tend to mutate more slowly than RNA viruses such as SARS-CoV-2 and HIV. Nevertheless, University of Alabama at Birmingham School of Medicine bioinformatician Elliot Lefkowitz, PhD, warned that a “worrisome mutation” could arise if the outbreak continues for much longer.
“I have no confidence that all the people who need to be tested are being tested,” she told Nature. She expressed concerns that people could resume risky behavior if they think the danger has passed.
Another question is whether currently available vaccines offer long-lasting protection. And though reported case numbers are down in the US and Europe, they are rising in parts of Africa and South America, Nature noted.
Gottlieb’s Dire Prediction
The decline in new infections followed dire warnings last summer about the possible consequences of the outbreak. In his New York Times op-ed, former Gottlieb criticized the CDC for being slow to test for the virus. He wrote, “[I]f monkeypox gains a permanent foothold in the United States and becomes an endemic virus that joins our circulating repertoire of pathogens, it will be one of the worst public health failures in modern times not only because of the pain and peril of the disease but also because it was so avoidable.”
At the time of his writing, Gottlieb was right to be concerned. On July 29, the CDC reported a seven-day moving average of 390 reported cases per day. According to the federal agency, a reported case “Includes either the positive laboratory test report date, CDC call center reporting date, or case data entry date into CDC’s emergency response common operating platform, DCIPHER.”
Quashing the outbreak, Gottlieb estimated, would have required about 15,000 tests per week among people presenting symptoms resembling monkeypox. But between mid-May and the end of June, he noted, the CDC had tested only about 2,000 samples, according to the federal agency’s July 15 Morbidity and Mortality Weekly Report (MMWR).
As a remedy, Gottlieb called on the Biden administration to re-focus the CDC’s efforts more on disease control “by transferring some of its disease prevention work to other agencies,” including the FDA.
Testing capacity has been boosted by inclusion of commercial laboratory companies and the fact that the virus spreads less easily than SARS-CoV-2
At the start of the SARS-CoV-2 pandemic, clinical laboratories were unprepared for unprecedented testing volumes. Fast forward to today, and the monkeypox outbreak has some clinical laboratory managers and pathologists wondering if they might again be faced with a surge in demand for monkeypox testing.
The good news is that so far the supply of tests appears adequate, especially compared to the early days of COVID-19.
“We’ve always had more capacity than we have had tests coming in,” Walensky noted. “To date, we’ve used about 14% to 20% of our capacity.”
During a hearing before the Senate Health, Education, Labor, and Pensions Committee on the current state of monkeypox testing capacity in the US, Rochelle Walensky, MD (above), Director at the CDC said, “We worked through commercial labs to expand testing across the country and simultaneously [offered] outreach and education to providers, clinicians, patients, and public health.” At the moment, access to clinical laboratory testing for monkeypox appears stable, but that could change as demand grows. (Photo copyright: CDC.)
Capacity Sits at 80,000 Tests Per Week in the US
When the monkeypox outbreak began, US medical laboratories could run 6,000 tests per week. At the time, this was more than sufficient, according to a White House press briefing.
However, since then, demand for testing has increased across the country to 80,000 tests per week. As part of that effort, the CDC partnered with five commercial laboratories to expand access to testing, according to the federal Department of Health and Human Services (HHS), Dark Daily reported in August.
Testing capacity also has kept up with demand thanks to biology. Monkeypox, which is in the same orthopoxvirus family of viruses as smallpox, has proven far less virulent than COVID-19, so fewer people are getting infected.
FDA Advises Against Monkeypox Saliva Test
Another boost to capacity in the future may come from new types of monkeypox tests.
Wired reported on Aug. 1 that Flow Health—a California company already distributing COVID-19 tests—has developed a monkeypox test that can detect the virus in saliva. This test would require patients to spit into a tube for a sample, and as such could be distributed for at-home use.
However, in a report released on July 15, the US Food and Drug Administration (FDA) advised providers to only take testing samples from lesions caused by the rash associated with monkeypox infection. The FDA stated that there is currently no clinical data to support the use of other monkeypox tests like Flow Health’s.
Monkeypox Testing Resources Scarce in Some Areas
At the moment, clinical laboratory testing capacity seems stable, however, roadblocks are appearing that may disrupt the availability of monkeypox tests for patients.
Although bringing on five commercial laboratories has increased US testing capacity, MedTech Dive reported on Aug. 10 that for some hospitals and laboratories, resources for monkeypox testing are scarce.
“Right now, there’s a lot of confusion in the community about where to get tested, where can people find treatment,” Robert Pitts, MD, an Infectious Diseases Specialist at Bellevue, told MedTech Dive. “There’s just no clear guidance because I think a lot of the different facilities and healthcare systems in New York are still trying to patch together pathways. … We’ve had to borrow space, borrow staff, which has been really, really challenging.”
During August, Bellevue took two primary care providers out of their normal clinical responsibilities to instead focus on monkeypox. And Pitts found himself dedicating four to five hours of his time to monkeypox-related issues, MedTech Dive reported.
“And so, I’m using my own time, because it’s a crisis, to respond to it,” he said.
The US healthcare system has been somewhat more efficient at getting monkeypox tests out to clinical laboratories than was the case with COVID-19. Moreover, new tests may be on the way. However, roadblocks exist that must be overcome to ensure monkeypox testing capability will meet growing demand.
South Asian nation aims to do what US, UK, and Europe failed to do during start of COVID-19 pandemic and slow spread of disease while case counts are low
With monkeypox quickly spreading around the world, India may be taking a lesson from western nations’ delayed response to COVID-19—including a sometimes slow availability of clinical lab testing for monkeypox—and preemptively increasing its national surveillance of the deadly social disease.
On Aug. 29, the Hindustan Times reported that in an attempt to slow the spread of monkeypox, India’s central government “has designated 15 viral research and diagnostic laboratories (VRDLs) spread across 13 states to monitor the incidence of monkeypox in the country.”
In the United States, the disease has spread with alarming speed, reaching all 50 states, as well as Washington, DC, and Puerto Rico. At 23,893 confirmed cases as of Sept. 14, the US now has the most cases in the world, according to the federal Centers for Disease Control and Prevention (CDC).
Reuters reported on Aug. 4 that the US Department of Health and Human Services (HHS) had declared a public health emergency. It was in May when monkeypox was detected in the United Kingdom (UK). Both the UK and several countries in Europe have struggled to control spread of the disease.
India hopes its decision to designate 15 VRDLs across 13 states to monitor the disease’s spread will enable it to do a better job than other countries at containing or eradicating monkeypox in the nation of 1.4 billion people, the Hindustan Times reported.
“The probability of containment is diminishing daily,” American infectious disease epidemiologist Anne Rimoin, PhD, a monkeypox expert at the UCLA Fielding School of Public Health, told STAT. “It’s really unfortunate because we do have the tools. This is not an unknown virus … We have vaccines that are already available, even vaccines with indications for monkeypox. Therapeutics. And we know what’s needed to be done.’’ Clinical laboratory testing for monkeypox will certainly increase over the coming months. (Photo copyright: KTLA.)
Keeping Up Their Guard
“Fortunately, India has not seen a surge in cases and the situation here is well under control. However, we cannot drop the guard just as yet. Therefore, a network of VRDLs has been established for surveillance purposes,” a top government expert told the Hindustan Times, seeking anonymity. “It will help pick signs early in case more cases get reported.”
As of Sept. 19, 2022, India reported just 12 cases of monkeypox resulting in one death, while, as noted above, the US had 23,892 confirmed cases and one death, according to CDC statistics. In the UK, confirmed cases totaled 3,552 with no deaths. And, as of that date, the European Union reported 19,379 confirmed cases.
Until recently, monkeypox was endemic only in West and Central Africa. India reported its first case of monkeypox on July 14. So far, most, but not all, of its cases have been related to international travel.
“The isolated cases of monkeypox reported in Delhi with no prior travel history emphasize the importance of tracing the source of the infection, perhaps transmission through rodent population,” Diwakar Kulkarni, PhD, former Director and Principal Scientist at the Indian Council of Agricultural Research, National Institute of High Security Animal Diseases, told Think Global Health.
Homosexuality a Vector in India
While India’s scientists are focused on containing the monkeypox outbreak, the country’s government may encounter societal roadblocks because of the disease’s connection with homosexuality. Gay sex is believed to be fueling the spread of the disease, ABC News reported. Until a Supreme Court of India ruling in 2018, gay sex was punishable by up to 10 years in prison in India.
Virologist and noted HIV expert Ishwar Gilada, MD, who opened India’s first AIDS clinic in 1986, told Bloomberg “anti-gay stigma” in India is causing male patients to avoid getting tested and treated for the disease. He said even before the first monkeypox cases were reported in India, two of his patients—a gay man and a man who identified as bisexual—refused to get tested because they feared being the first monkeypox case in the country.
“They are going underground,” Gilada told Bloomberg.
Did the US Wait Too Long to Begin Testing for Monkeypox?
The rapid growth in cases worldwide and the geographic spread of the disease has left global health experts pessimistic monkeypox can be contained.
NPR reported in June that some experts believe public health agencies ran too few tests in the early months of the outbreak because state health officials used a narrow definition of monkeypox when determining who qualified for testing, and that the US had “dropped the ball” on monkeypox testing.
As of Sept. 19, 2022, there were 62,406 confirmed cases worldwide, according to the CDC.
As clinical laboratories attempt to recover from the workload created by the COVID-19 pandemic, monkeypox appears to be the next endemic to test the mettle of lab professionals. Only time will tell if America and other western nations failed to act as expeditiously as India in curbing spread of this latest deadly disease.
Researchers surprised that process designed to detect SARS-CoV-2 also identifies monkeypox in wastewater
Early information about an outbreak in a geographical region can inform local clinical laboratories as to which infectious agents and variants they are likely to see when testing patients who have symptoms. To that end, wastewater testing has become a rich source of early clues as to where COVID-19 outbreaks are spreading and how new variants of the coronavirus are emerging.
Ongoing advances in genetic sequencing and digital technologies are making it feasible to test wastewater for infectious agents in ways that were once too time-consuming, too expensive, or simply impossible.
“Before wastewater sequencing, the only way to do this was through clinical testing, which is not feasible at large scale, especially in areas with limited resources, public participation, or the capacity to do sufficient testing and sequencing,” said Knight in a UCSD press release. “We’ve shown that wastewater sequencing can successfully track regional infection dynamics with fewer limitations and biases than clinical testing to the benefit of almost any community.” (Photo copyright: UC San Diego News.)
Same Process, Different Virus
Following August’s declaration of a state of emergency by California, San Diego County, and the federal government, UCSD researchers added monkeypox surveillance to UCSD’s existing wastewater surveillance program.
“It’s the same process as SARS-CoV-2 qPCR monitoring, except that we have been testing for a different virus. Monkeypox is a DNA virus, so it is a bit of a surprise that our process optimized for SARS-CoV-2, which is an RNA virus, works so well,” said Rob Knight, PhD, Professor of Pediatrics and Computer Science and Engineering at UCSD and one of the lead authors of the study in the press release.
According to the press release, RNA sequencing from wastewater has two specific benefits:
It avoids the potential of clinical testing biases, and
It can track changes in the prevalence of SARS-CoV-2 variants over time.
In 2020, at the height of the COVID-19 pandemic, scientists from the University of California San Diego and Scripps Research looked into genetic sequencing of wastewater. They wanted to see if it would provide insights into levels and variants of the SARS-CoV-2 within a specific community.
Individuals who have COVID-19 shed the virus in their stool.
The UCSD/Scripps researchers deployed commercial auto-sampling robots to collect wastewater samples at the main UCSD campus. They analyzed the samples for levels of SARS-CoV-2 RNA at the Expedited COVID-19 Identification Environment (EXCITE) lab at UCSD. After the success of the program on the campus, they extended their research to include other facilities and communities in the San Diego area.
“The coronavirus will continue to spread and evolve, which makes it imperative for public health that we detect new variants early enough to mitigate consequences,” said Knight in a July press release announcing the publication of their study in the journal Nature, titled, “Wastewater Sequencing Reveals Early Cryptic SARS-CoV-2 Variant Transmission.”
Detecting Pathogens Weeks Earlier than Traditional Clinical Laboratory Testing
In July, the scientists successfully determined the genetic mixture of SARS-CoV-2 variants present in wastewater samples by examining just two teaspoons of raw sewage. They found they could accurately identify new variants 14 days before traditional clinical laboratory testing. They detected the presence of the Omicron variant 11 days before it was first reported clinically in the community.
During the study, the team collected and analyzed 21,383 sewage samples, with most of those samples (19,944) being taken from the UCSD campus. They performed genomic sequencing on 600 of the samples and compared them to genomes obtained from clinical swabs. They also compared 31,149 genomes from clinical genomic surveillance to 837 wastewater samples taken from the community.
The scientists distinguished specific viral lineages present in the samples by sequencing the viruses’ complete set of genetic instructions. Mutational differences between the various SARS-CoV-2 variants can be minute and subtle, but also have notable biological deviations.
“Nothing like this had been done before. Sampling and detection efforts began modestly but grew steadily with increased research capacity and experience. Currently, we’re monitoring almost 350 buildings on campus,” said UCSD’s Chancellor Pradeep Khosla, PhD, in the July press release.
“The wastewater program was an essential element of UC San Diego Health’s response to the COVID pandemic,” said Robert Schooley, MD, Infectious Disease Specialist at UC San Diego Health, in the press release. Schooley is also a professor at UCSD School of Medicine, and one of the authors of the study.
“It provided us with real-time intelligence about locations on campus where virus activity was ongoing,” he added. “Wastewater sampling essentially allowed us to ‘swab the noses’ of every person upstream from the collector every day and to use that information to concentrate viral detection efforts at the individual level.”
Monkeypox Added to UCSD Wastewater Surveillance
In August, UCSD officially added the surveillance of the monkeypox virus to their ongoing wastewater surveillance program. A month earlier, the researchers had discerned 10,565.54 viral copies per liter of wastewater. They observed the levels fluctuating and increasing.
On August 2, the scientists detected 189,309.81 viral copies per liter of wastewater. However, it is not yet clear if the monitoring of monkeypox viral loads in wastewater will enable the researchers to accurately predict future infections or case rates.
“We don’t yet know if the data will anticipate case surges like with COVID,” Knight said in the August UCSD press release announcing the addition of monkeypox to the surveillance program. “It depends on when the virus is shed from the body relative to how bad the symptoms are that cause people to seek care. This is, in principle, different for each virus, although in practice wastewater seems to be predictive for multiple viruses.”
Utilization of genetic sequencing of wastewater sampling will continue to develop and improve. “It’s fairly easy to add new pathogens to the process,” said Smruthi Karthikeyan, PhD, an environmental engineer and postdoctoral researcher in Knight’s lab who has overseen wastewater monitoring at UC San Diego. “It’s doable on short notice. We can get more information in the same turnaround time.”
Thus, clinical laboratories engaged in testing programs for COVID-19 may soon see the addition of monkeypox to those processes.
