Asymptomatic monkeypox virus infections among male sexual health clinic attendees in Belgium
Authors: De Baetselier Irith , Van Dijck Christophe , Kenyon Chris , Coppens Jasmine , Van den Bossche Dorien , Smet Hilde , Liesenborghs Laurens , Vanroye Fien , de Block Tessa , Rezende Antonio , Florence Eric , Vercauteren Koen , Van Esbroeck Marjan ,   the Monkeypox study group
Published: July 2022

AbstractBackgroundMonkeypox is transmitted by close contact with symptomatic cases, and those infected are assumed to be uniformly symptomatic. Evidence of subclinical monkeypox infection is limited to a few immunological studies which found evidence of immunity against orthopoxviruses in asymptomatic individuals who were exposed to monkeypox cases. We aimed to assess whether asymptomatic infections occurred among individuals who underwent sexually transmitted infection (STI) screening in a large Belgian STI clinic around the start of the 2022 monkeypox epidemic in Belgium.MethodsAnorectal and oropharyngeal swabs collected for gonorrhoea/chlamydia screening from May 1 until May 31, 2022 were retrospectively tested by a monkeypox-specific PCR. Cases with a positive PCR result were recalled to the clinic for case investigation, repeat testing and contact tracing.FindingsIn stored samples from 224 men, we identified three cases with a positive anorectal monkeypox PCR. All three men denied having had any symptoms in the weeks before and after the sample was taken. None of them reported exposure to a diagnosed monkeypox case, nor did any of their contacts develop clinical monkeypox. Follow-up samples were taken 21 to 37 days after the initial sample, by which time the monkeypox-specific PCR was negative, likely as a consequence of spontaneous clearance of the infection.InterpretationThe existence of asymptomatic monkeypox infection indicates that the virus might be transmitted to close contacts in the absence of symptoms. Our findings suggest that identification and isolation of symptomatic individuals may not suffice to contain the outbreak.FundingInstitutional fundingResearch in contextEvidence before this studySimilar to smallpox, monkeypox is transmitted through close contact with symptomatic cases, and 100% of those infected are assumed to develop symptoms. These features imply that an outbreak in the general population tends towards extinction with relatively minor hygienic measures, as observed in several outbreaks in endemic regions. If, however, asymptomatic transmission occurs, the outbreak becomes much more difficult to contain.We searched PubMed and Google Scholar for evidence of asymptomatic human monkeypox, using the search terms “monkeypox” AND (“asymptomatic” OR “subclinical”), and included peer-reviewed reports published until June 17, 2022. We identified seven original reports in three different epidemiological settings which reported indirect, immunological evidence of asymptomatic monkeypox infection in a small number of people who were exposed to the virus. We did not find any study that provided direct evidence of the virus in asymptomatic individuals.Added value of this studyBy retrospectively screening clinical samples collected for sexually transmitted infection screening in our centre throughout May 2022 with a monkeypox-specific PCR, we found evidence of asymptomatic monkeypox virus infection in three individuals.Implications of all the available evidenceThe existence of asymptomatic monkeypox infection indicates that the virus may be transmitted in the absence of symptoms. This risk can be further quantified by studying viral dynamics in contacts of symptomatic and asymptomatic monkeypox cases. Our findings suggest that identification and isolation of symptomatic individuals may not suffice to contain the outbreak.