Monkeypox is transmitted by close contact with people who have symptomatic infection, and all those infected are assumed to show symptoms. But a recent study has found that people can be infected with monkeypox without showing any of the typical or atypical symptoms. The preprint has been posted in medrXiv server, which is yet to be peer-reviewed.
The study found three men tested positive for monkeypox but have no symptoms whatsoever. “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,” the preprint notes.
Symptoms assumed
Similar to smallpox, everyone who is infected with monkeypox is expected to develop symptoms, and the virus is considered to spread through close contact with people who show symptoms. Since every individual infected with monkeypox is assumed to develop symptoms, and since close contact is most often needed for the virus to spread, it is considered that staying away from infected people and maintaining simple hygienic measures can halt the spread of monkeypox virus, as observed in several outbreaks in endemic regions.
But asymptomatic transmission can change and challenge the efforts to contain the monkeypox outbreak, which till July 4 has been reported in 6,027 people across 59 countries, including those in endemic countries in Africa.
According to the World Health Organization (WHO), the “extent to which asymptomatic infection may occur is unknown”.
The researchers retrospectively screened 224 clinical samples collected for sexually transmitted infection (gonorrhea or chlamydia) throughout the month of May 2022 with a monkeypox-specific PCR. And they found evidence of asymptomatic monkeypox virus infection in three individuals. They tested anorectal and/or oropharyngeal samples collected from 224 people at the HIV/STI clinic of the Institute of Tropical Medicine in Antwerp, Belgium.
All the three men who tested positive for monkeypox were informed about their diagnosis and recalled to the clinic for additional case investigation and contact tracing. Follow-up samples were collected from all three men when they were recalled to the clinic. The repeat samples collected 21-27 days later were all negative.
At the time they were recalled to the clinic, none of them showed signs or symptoms of monkeypox and all denied having noticed any symptoms during the two months prior or three weeks after initial sampling, the authors write. All three men had condomless sexual intercourse with at least one male partner within a few days to one month before the sampling.
The authors note that one of the three men who tested positive for monkeypox and was asymptomatic predated the first detected symptomatic case in Belgium by several days. There was no epidemiological link to any other monkeypox case, nor did he report international travel or participation in mass gatherings.
“This may indicate that monkeypox virus circulated among asymptomatic individuals in Belgium before the outbreak was detected,” they write.
The researchers also note that the cycle threshold (Ct) values in anorectal samples taken from the asymptomatic men were “similar or lower than those in samples taken from typical monkeypox skin lesions”. Based on the lower Ct values of anorectal samples, the researchers note that the “anorectal mucosa of asymptomatic cases may be as infectious as skin lesions of symptomatic cases”.
Similar viral loads
The anorectal cycle threshold values of symptomatic cases were in the same range as those who did not show symptoms. This, according to the authors, suggests similar viral loads immaterial of whether they showed symptoms or not. “This would support the hypothesis that monkeypox virus can be transmitted via anal sex, even in the absence of symptoms,” they write.
They also add, “It is possible that in the current outbreak in non-endemic settings, asymptomatic carriership plays a more substantial role in virus transmission… In the current outbreak, the skin eruption often remains localised at the site of inoculation, and the mode of transmission seems to be sexual. In this case, asymptomatic carriership, especially with high viral loads in the anal mucosa, could, therefore, be a significant driver of transmission.”
Unnoticed skin lesions
While they state that transmission of the virus in the absence of noticeable symptoms might explain why self-isolation at symptom onset has been insufficient to halt the epidemic thus far, they caution that the three men may not have been completely free of symptoms at first presentation when samples were collected. This is because no clinical examination was conducted then and no symptoms were reported then due to recall bias or because the small skin lesions went unnoticed.
But more studies are needed to confirm or refute the findings of these researchers. Meanwhile, more efforts should be directed at identifying asymptomatic cases through increased contact tracing, and screening high risk populations, they say.
