Monkeypox is a viral illness that is endemic in several parts of Africa, but has recently caused an outbreak in many countries around the world.
Until now, it was thought to be transmitted by close contact with symptomatic cases, and infection was assumed to be symptomatic in all patients. More recently, however, specific antibodies were found in asymptomatic but exposed individuals, indicating that they had a subclinical infection at some point.
A new preprint posted to the medRxiv* preprint server reports on the incidence of subclinical infection among individuals attending a sexual health clinic in Belgium. The findings may indicate the need for wider testing and isolation policies among people exposed to symptomatic monkeypox cases.
Earlier outbreaks of monkeypox have been treated on the premise that all infections are symptomatic, so that isolation of symptomatic cases brings transmission to an end.
An outbreak in the general population tends towards extinction with relatively minor hygienic measures.”
The current clusters of infections in countries outside Africa, where the virus was not endemic in previous years, show some significant differences. As of now, over 25,000 cases have been documented, far exceeding any previous outbreak.
Most cases have been among men who have sex with men (MSM). Many symptoms related to the anus or external reproductive organs, and in some patients, symptoms are very mild.
Some researchers have reported high viral loads in samples from the anal and genital regions, saliva, and semen. These facts seem to point to the possibility of sexual transmission, but also raise the question of asymptomatic transmission.
Earlier literature showed evidence of asymptomatic monkeypox infection, in the form of seropositivity among people exposed to the virus but without signs of infection. The current study deals with an attempt to provide direct evidence of the presence of the virus in asymptomatic individuals with a history of contact with known cases.
The scientists used a polymerase chain reaction (PCR) assay specific for monkeypox to test samples collected during sexually transmitted infection (STI) screening at a sexual health clinic, in May 2022. These samples were screened retrospectively, as none of the donors had presented with monkeypox diagnoses.
The researchers detected monkeypox viral genetic material in three patients out of ~225 men who were routinely tested for gonorrhea or chlamydia infection. They used anorectal and/or oropharyngeal samples, sometimes combined with first-void urine samples, at the HIV/STI clinic of the Institute of Tropical Medicine in Antwerp.
Four patients were positive for monkeypox DNA, in four anorectal swabs. This was confirmed by repeat PCR and gel electrophoresis. Of the four, one had a perianal rash that was thought to be due to herpes simplex, but the other three were asymptomatic at the time of sampling. Due to the lack of symptoms, no physical examination was carried out and the anorectal swabs were collected by the men themselves.
Of the three asymptomatic positive cases, none had been vaccinated against smallpox, all were 30-50 years of age, had human immunodeficiency virus (HIV) under good control and had multiple STIs in their past history.
The results led to the men being recalled, within 37 days of the first sample. Repeat swabs were negative for the disease.
None had developed any monkeypox symptoms from 2 months before to 3 weeks after the first sampling. All had a history of unprotected sex with one man, at least, during the month prior to initial sampling, and three had sex during trips abroad within the 2 weeks before samples were given.
None of the partners had symptomatic monkeypox, as far as could be ascertained.
The findings of the study indicate that asymptomatic monkeypox is a reality, with three of four positive tests coming from asymptomatic men, corroborating earlier indirect proof of this phenomenon. One of these men had a positive sample before the first symptomatic Belgian case, but had no history of foreign travel or exposure to a known case, indicating that the earliest documented symptomatic case in Belgium may have occurred against a background of community transmission.
Further study will be required to understand if the virus is present in other body sites in asymptomatic individuals. However, it seems plain that with high viral loads in anorectal swabs, irrespective of the presence of skin lesions, anal sexual contact could be just as infectious as contact with skin lesions in symptomatic patients.
This would support the hypothesis that MPXV can be transmitted via anal sex, even in the absence of symptoms.”
If so, asymptomatic transmission is probably more important than symptomatic, in the current outbreak. This could explain why self-isolation proved inefficient at halting the spread of the virus.
Earlier outbreaks saw viral spread from patients with extensive rashes to household or healthcare contacts, via direct contact with the virus in skin lesions or droplets. However, the present outbreak is marked by localized skin rashes, at the inoculation site, through sexual contact via the anal mucosa.
Future studies must include physical, serological, PCR-based and epidemiological assessments of both cases and contacts, to answer questions like: What percentage of infections are asymptomatic; what body sites are infectious; and can infection be prevented by condoms or vaccines.
At present, however, MSM and the general population must be made aware of the potential for asymptomatic transmission, including sexual transmission from asymptomatic carriers. A re-evaluation of the high-risk behavior underlying such spread should be encouraged so that public health is not taxed unnecessarily by easily preventable illnesses.
Contact tracing and screening of high-risk populations are other useful measures. Vaccines will also probably be required for this group.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.