Asymptomatic viral shedding of mpox virus: What do we know?

Mpox (previously known as monkeypox) is a disease caused by the monkeypox virus (MPXV), an orthopoxvirus belonging to the Poxviridae family. ¹ Initially identified in 1970, the virus was primarily transmitted through zoonosis and caused outbreaks in several African countries. ² The emergence of the 2022 epidemic revealed a new transmission pattern. Since the rash was most frequently localized to the anogenital area in many patients ³ and the majority of patients were men who have sex with men (MSM),^3,4 it was suggested that close contact during sexual activities may be driving this epidemic. ⁴ As of November 30, 2024, 117,663 cases of mpox have been reported worldwide, with 263 lab-confirmed deaths. ⁵

Confirmed reports of mpox transmission through asymptomatic contacts are still lacking. However, several studies have detected positive mpox DNA in the pharyngeal and/or rectal swabs of asymptomatic individuals, most of whom were MSM.^6–14 Some of these samples exhibited replication-competent viruses capable of causing a cytopathic effect ¹² and, theoretically, could be infectious. A meta-analysis suggested that 10% of patients infected with the MPXV might be asymptomatic. ¹⁵ A study conducted on high-risk poplations in Spain found that out of 113 participants, seven tested positive for MPXV (6.19%). ¹¹ Three were asymptomatic before testing (2.65%), and one later developed fever, exhaustion, sore throat, and skin lesions within 21 days. Viable MPXV viruses were obtained only from individuals who reported symptoms, ¹¹ raising questions about the significance of positive results in asymptomatic individuals. Whether testing high-risk individuals regardless of symptoms presence would be cost-effective is debatable. Several studies tested samples from high-risk patients and found either no positive results or very low detection rates.^7,16–18

While the significance of asymptomatic viral shedding is still not fully understood, presymptomatic viral shedding has been demonstrated in a study involving 25 participants who were recent contacts of mpox patients. ¹⁹ Viral DNA was detected as early as 4 days before symptom onset in five patients, three of whom had replication-competent virus demonstrated in the presymptomatic phase. ¹⁹ Two patients who were possibly infected remained asymptomatic. It is also unclear how long viral shedding continues after symptoms onset. In one study, positive PCR results for MPXV were detected in the semen of a patient up to 19 days after symptoms onset, with replication-competent virus isolated at 6 days after onset. ²⁰ These findings highlight the high risk of transmission in presymptomatic individuals and underscore the importance of abstaining from sexual activities during the incubation period, regardless of symptoms.

Guidelines recommend vaccination for at-risk populations. One study found that vaccination may contribute to asymptomatic or unrecognized infections. ¹³ Among 1663 patients tested, 18 individuals (1.1%) had asymptomatic or subclinical mpox based on positive rectal or pharyngeal tests. ¹³ Compared to unvaccinated patients, those who received one or two doses of the Modified Vaccinia Ankara (MVA) vaccine were 4.4 and 11.9 times more likely to have asymptomatic versus symptomatic mpox, respectively. ¹³ Nonetheless, considering the likely limited utility of testing asymptomatic individuals, vaccination remains a crucial strategy in combating this epidemic.

A deeper understanding of MPXV transmission patterns will inform local and international prevention strategies and responses to this significant public health threat and potentially limit future outbreaks.