In June, when it became clear that the U.S. monkeypox outbreak that had begun a month before was not going to just peter out, federal officials met the outbreak with confidence. The pool of at-risk people seemed to be relatively shallow—mostly limited to men who had sex with other men, anyone who had other close contact with a confirmed or suspected case, and anyone who had recently traveled to a country where monkeypox was known to be circulating. A testing infrastructure for monkeypox was already in place through the U.S. Centers for Disease Control and Prevention (CDC) and its Laboratory Response Network (LRN), a collection of 67 federal labs in 48 states, capable of processing more than 8,000 monkeypox tests per week.
That might have sounded like a lot at the time. Now, just a month later, the outlook looks a lot less optimistic—and that’s largely because too many obstacles still stand in the way of getting people tested and therefore treated. The testing failures of monkeypox are similar to those that inhibited a robust early response to COVID-19 in the U.S., experts say. As of July 21, 2,593 cases of monkeypox have been diagnosed in 44 states, the District of Columbia, and Puerto Rico, according to the CDC. The actual numbers are probably far larger.
“Most likely, we are just seeing the tip of the [monkeypox] iceberg,” says Michael Mina, chief science officer at eMed, a home testing and treatment company. (Mina was formerly assistant professor of epidemiology at Harvard T. H. Chan School of Public Health.) “We know that this is a very widespread virus in our population at the moment, at least among certain groups.”
Boghuma Titanji, assistant professor of infectious diseases at Emory University in Atlanta, agrees. “We are not capturing the extent to which community spread is happening in the United States. We’re not fully detecting the spread, and this is very much reminiscent of the early days of COVID.”
There aren’t enough tests
The LRN labs weren’t nearly enough to meet the crushing demand for monkeypox testing in some parts of the country. On June 22, the U.S. Department of Health and Human Services (HHS) authorized five private laboratories—Aegis Science, Labcorp, the Mayo Clinic Laboratories, Quest Diagnostic, and Sonic Healthcare—to perform testing as well. With the help of the private labs, the nationwide weekly testing capacity has increased nearly 10-fold, federal health officials said at a July 15 press conference held by the CDC, HSS and the Food and Drug Administration (FDA)—from 8,000 to 70,000.
Even that’s not adequate—and hotspots are struggling to get a share of tests proportionate to the outbreak there, which was also true early on in the pandemic. “The New York City [lab] does under 20 tests a day, and they are at or near that capacity,” says Joseph Osmundson, a molecular biologist at New York University. “Whereas in Oklahoma City, are you going to have the same need for monkeypox testing right now? No.” According to the CDC, New York state currently has 581 confirmed cases of monkeypox compared to just five in Oklahoma. That leaves some labs stretched to overcapacity while others stand idle.
Monkeypox testing takes too long
Current tests can detect only orthopoxvirus, the larger family of viruses to which monkeypox belongs. Any positive orthopoxvirus tests then have to be sent to the CDC to confirm that monkeypox is indeed the particular virus the individual is carrying.
That bottleneck increases the chances that the virus can get passed on. “What’s important to understand in any infectious-disease outbreak is that time is spread,” says James Krellenstein, an AIDS activist and co-founder of the group PrEP4ALL, an LGBTQ advocacy group that is now working to help the community deal with monkeypox. “When we allow ourselves to be blinded to the extent of the outbreak, we allow this virus to spread, and we allow our communities to get harmed.”
On July 15, CDC director Dr. Rochelle Walensky said that while positive results will still be sent to the CDC for confirmation, the initial result—the positive orthopoxvirus test—will be counted as a presumptive case of monkeypox, since it is the only orthopoxvirus in wide circulation at present. That positive diagnosis is also a signal that the infected person should begin home isolation and continue until all lesions have healed, scabs have fallen off and a new layer of skin has formed.
Eligibility was too strict in the early response
Monkeypox remains more prevalent in men who have sex with other men, so in May and early June, testing was reserved largely for people in that category. (When COVID-19 tests were scarce, they were also limited to specific populations.) Yet monkeypox can also be spread by less intimate physical contact with someone who has a monkeypox lesion, rash or scab; respiratory contact during prolonged face-to-face proximity, such as that which occurs during kissing or cuddling; or even by touching clothing or linens that have been in contact with an infectious monkeypox rash or secretions. It can also be spread from pregnant mother to child through the placenta. So far, eight women in the U.S. have tested positive for monkeypox. “We have seen reports in Europe of cases in women, too,” says Titanji. At least two cases have been reported in children outside of the U.S., as well.
Now, the walls to testing in those groups have come down. “We’re now testing outside of that population [of men who have sex with men,]” said Jennifer McQuiston, a doctor of veterinary medicine and the incident manager of the CDC’s monkeypox response team, at the July 15 press conference. “We’re not really seeing many positives in those people, so it continues to suggest that the outbreak is happening in the focus population.”
Only people with lesions can get tested—even though other symptoms often develop first
“Moving tests into clinics was a great step forward,” says Krellenstein. “But we wasted weeks and weeks when we had very little testing capacity.” That, Krellenstein worries, suggests a large population of infected people who don’t yet know they’re carrying the virus, since monkeypox has an incubation period of up to two weeks.
The virus builds up in the body relatively gradually. While it may be present in bodily fluids like saliva and urine, it is in such low concentrations that current tests can’t detect it reliably. That means that monkeypox tests don’t work at the first sign of symptoms, which may include fever, headache, chills, swollen lymph nodes, and a rash nearly anywhere on the body. A direct swab of a suspected monkeypox lesion is thus the only reliable way to test for the disease.
“By definition, if you don’t have a lesion, it’s hard to do the test,” said McQuiston. “There are no approved tests to do [it] other ways.”
Once infected people develop lesions and show up at clinics, test results can take days to return. Urgent care centers take about three days to return a result, says Osmundson—but urgent care centers often also require insurance or payment on the spot, which excludes many lower income people. In New York City, where Osmundson works, the Department of Health will conduct tests for free, but the turnaround time can reach 10 days.
“There are significant backlogs in public-health access in cities like New York and San Francisco,” Osmundson says, which are both monkeypox hotspots. “That’s leading to very serious delays in getting results.”
As we saw with COVID-19, waiting days for a positive test result can be dangerous—not only for the infected person, but also for the community at large. Clinicians generally ask patients to isolate at home until they know their results, Osmundson says, but as with COVID-19, there is nothing a health care worker can do to enforce quarantining.
Slow testing delays treatment
Accessing treatment during the waiting period is another issue. Tecovirimat—known as TPOXX—is a drug approved for the treatment of smallpox, and is now the first-line drug for monkeypox as well. The medication is effective, and—much like the COVID-19 antiviral Paxlovid—it works best when symptoms first start; the faster a patient takes it after monkeypox lesions appear, the quicker the infection can be controlled.
But in most places, doctors do not prescribe the drug until a positive monkeypox test is returned. New York City offers an exception to the rule, with the local Department of Health permitting TPOXX use “at the discretion of the treating clinician” even before a positive test is returned. The CDC does not take the same position, leaving patients elsewhere in the country to wait for treatment until their infection is confirmed.
Lesions may have to be in certain spots for people to get tested
Monkeypox can appear nearly anywhere on the body, but earlier on in the outbreak, says Osmundson, “the CDC indicated that only external lesions could be swabbed to be tested.” That guidance was out of step with medical reality, since internal lesions—particularly in the anus or rectum—can also occur as a result of sexual transmission.
One monkeypox patient who Osmundson says was a friend of his, and whose case he followed closely, was in excruciating pain from rectal lesions, yet had to wait a week before being approved for a test—a week during which he was initially told his problem might be cancer, not monkeypox. “It took an organized campaign by three people working 12-hour days before he was finally approved for a test,” says Osmundson. “It was unbelievable how difficult it was.” The patient was indeed confirmed to have monkeypox.
Not every health care provider has had that experience, however, and plenty still rely on the old CDC guidance and the directions in the test kit itself, swabbing only external lesions and looking to different diagnoses for blisters that occur internally. “There’s confusion on the user end of the test,” says Osmundson, “with the caregiver asking ‘Am I even allowed to give the patient the result if the test is not approved for internal lesions?’”
These roadblocks to adequate testing create exactly the kind of environment in which viruses thrive and spread, as we’ve seen all too recently with COVID-19. “The vast majority of my epidemiologist friends believe this virus is not going away,” says Osmundson. “We need to [go] pedal to the metal with all possible interventions now.”
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Contributor: Jeffrey Kluger