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On Aug. 14, 2024, the World Health Organization (WHO) of international concern. It is the second time in 2 years that WHO has taken this step. The 2022 outbreak consisted of approx. . According to the U.S. Centers for Disease Control and Prevention (CDC), 32,000 of these cases occured in the U.S.

Now, an ongoing outbreak that orginated in the Democratic Republic of the Congo (DRC) has spread to 13 other African countries, as well as parts of Asia and Europe, and case numbers are reaching unprecidented levels. According to the Africa CDC,  compared to the same time period in 2023, and the strain that is spreading (clade I monkeypox virus (MPXV)) is more deadly than the strain that was responsible for the 2022 outbreak (clade II MPXV).

Altogether, these facts necessitate proactive diagnostic and preventative steps in order to contain the outbreak and offer hope to those suffering from the disease.

How Do We Contain Mpox Outbreaks?

If the early days of the COVID-19 pandemic taught us anything, it’s that timely and accurate diagnosis are critical to our ability to slow transmission of the virus. Unlike SARS-CoV-2, which was a novel virus when it emerged in late 2019, mpox virus has been around for a bit. It is a member of the Orthopoxvirus genus and relative of smallpox. The virus was first discovered causing pox-like disease in laboratory monkeys in 1958 and the first case of human infection was reported in 1970. This means that previously developed diagnostic, treatment and prevention strategies are available and expected to benefit current efforts to contain outbreaks.

Yet, a few noteworthy differences between current outbreaks and what has been historically observed in endemic countries, have generated . Public messaging about what to do if one comes in contact with the virus is, therefore, especially critical during this time. How is mpox diagnosed? When and where should one get tested? Can vaccines be administered after exposure?

When to Get Tested for Mpox

Contact your physician and seek testing if either of the following occurs:

1. You have known exposure (have been in close contact) with someone who has been diagnosed with mpox.
2. You develop symptoms of the disease.

Mpox Transmission

Mpox virus is less transmissible than SARS-CoV-2, as it is primarily spread through direct person-to-person contact, either via respiratory droplets or exposure to infectious lesions or other bodily fluids. The virus is not known to linger in the air like SARS-CoV-2. It may also be passed perinatally and may be contracted by touching contaminated surfaces. Mpox virus DNA has been .

Mpox Symptoms

Symptoms of mpox include fever, chills, headaches, muscle aches, fatigue, swollen lymph nodes and a painful rash that characteristically appears as raised bumps on the skin and tends to be distributed on the face, extremities and genitals. As the disease progresses, these bumps fill with pus and fluid and become umbilicated. They will eventually ulcerate, scab and fall off.

Like many viruses, mpox cannot be conclusively diagnosed by symptoms alone. This is because many mpox symptoms closely resemble those of other rash-producing illnesses and maladies, such as chickenpox, measles, bacterial skin infections and even hives/allergic reactions to medication. Confirmatory laboratory testing is therefore essential for accurate diagnosis.

What Type of Mpox Tests are Available?

Polymerase Chain Reaction

Nucleic acid amplification testing, also known as molecular testing and polymerase chain reaction (PCR), relies on the extraction of genetic material from a patient specimen, followed by subsequent amplification with pathogen-specific primers. If the virus is present in the sample, it will be detected upon amplification, revealing whether the patient is actively infected at the time of testing. Due to the sensitivity and accuracy of this technique, PCR is the preferred laboratory test for mpox diagnosis.

According to WHO, are considered optimal diagnostic samples. Lesion biopsies may also be used, but , because the virus resides in the blood for only a short period of time during the course of infection.

Rapid Antigen and Serology?

Importantly, methods that rely on the detection of antibodies (e.g., serology) or antigens (e.g., lateral flow and/or rapid antigen testing) are of limited value for mpox diagnosis because the virus demonstrates significant cross-reactivity with other orthopoxviruses (e.g., , , , ). This means that the viruses in the Orthopoxvirus genus are antigenically similar, which makes them difficult to differentiate from one another, and the antibodies that are formed in defense of such pathogens demonstrate a similar overlap. This is further complicated by cross-reactive immune responses that may be induced by vaccinia-based vaccination, leading to false positives in individuals who have recently or previously received the smallpox vaccine. Not surprisingly, this serologic cross-reactivity remains a significant barrier to the development of new diagnostic techniques.

The key takeaway is that, for now, confirmatory testing for mpox must be performed in the lab. There is no at-home option. And while samples may be collected by most health care providers, they must be sent to a public health laboratory or a properly equipped commercial lab for analysis.

Mpox Exposure and Next Steps

Monitor Symptoms and Seek Testing

If you believe you have been exposed to someone who is infected with mpox virus, the CDC recommends , as the typical incubation period is 1-2 weeks, but it may take up to 3 weeks for symptoms to appear. If symptoms do develop, immediately self-isolate and contact your health care provider for further guidance.

Get Vaccinated

Fortunately, when properly administered before or directly after a recent exposure, vaccines can be effective at preventing mpox illness. The CDC recommends for the best chance of preventing disease. When received up to 14 days post exposure, vaccines may be less effective at preventing disease but will likely continue to reduce symptoms. After the onset of symptoms, vaccination is not expected to be particularly beneficial to the current course of infection.

As we seek to slow the spread of mpox around the globe, increased testing capacity and vaccination will be critical. So will science communication efforts. It is important to warn, inform and support at-risk communities, while dispelling stigmatization through educational resources and public messaging. Mpox can be transmitted to anyone and remains a public health threat to all people. Scientists must communicate in ways that educate and equip individuals to make best-informed decisions to protect their health and communities.

Will we be able to apply lessons learned from the COVID-19 pandemic to efficiently diagnose and subsequently provide timely and targeted treatment and prevention options for infected individuals? Time will tell.

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