New evidence of mpox virus transmission before onset of symptoms

In a recent study posted to the medRxiv* preprint server, researchers extensively followed-up high-risk contacts of clade IIb mpox (MPX) virus (MPXV)-infected patients to evaluate the risk of MPX after MPXV exposure and to characterize early MPXV infections.

Study: Pre- and asymptomatic viral shedding in high-risk contacts of monkeypox cases: a prospective cohort study. Image Credit: Dotted Yeti/Shutterstock
Study: Pre- and asymptomatic viral shedding in high-risk contacts of monkeypox cases: a prospective cohort study. Image Credit: Dotted Yeti/Shutterstock

Studies have reported that clade IIb MPXV is transmitted readily during sexual intercourse, even before the onset of MPX symptoms, and that pre-symptomatic spread could lead to nearly half of MPX cases. However, the pre-symptomatic nature of MPXV shedding and the sites and timing of viral shedding requires further investigation.

About the study

In the present prospective cohort study, researchers prospectively followed up on 25 high-risk contact individuals of confirmed MPXV-positive patients between June 24 and July 31, 2022. They presented their virological and clinical characteristics in the period between MPXV exposure and MPX diagnosis.

The study comprised 25 participants who self-collected samples daily, such as saliva, genital swabs, and anorectal swabs, and maintained a symptom diary. Additionally, every week, the participants were examined clinically, and their oropharyngeal swab samples and blood samples were collected. Further, individuals who experienced usual MPXV infection symptoms, such as proctitis, dermatological lesions, tonsillitis, and urethritis, were assessed during their clinical visits on an ad hoc basis.

The participants were followed-up until the development of typical MPXV infection symptoms and received a polymerase chain reaction (PCR)-confirmed MPX diagnosis, with cycle threshold (Ct) values below 34. Furthermore, PCR cut-offs of high sensitivity and specificity for MPX were determined, and the former cutoff was based on specificity assessments using saliva specimens of 52 uninfected control individuals.

Additionally, samples with Ct values between the two cut-offs were confirmed by repeating the PCR analysis and performing a PCR melting curve analysis. Based on the MPXV-PCR Ct cut-off values, the participants’ MPXV infection status was determined as uninfected, probably infected, or definitely infected.

Results

The median values for participant age and follow-up duration were 43.0 years and 16 days (i.e., until 23 days post-most recent high-risk contact), respectively. Nearly all (96%) individuals self-identified as men who have sex with men (MSM). Eighteen (72%) individuals documented sexual intercourse with index cases. Seven individuals (28%) were high-risk but non-sexual contacts, of which five were household members, and two had long-term cutaneous contact with MPX cases.

The median value for the duration between the most recent MPXV exposure and the inclusion of the study cohort was nine days. Five individuals were PEV (post-exposure vaccination) recipients, and six had been administered smallpox vaccinations in their childhood. In total, 1,108 specimens, including 323, 323, 312, 70, 66, and 14 saliva, anorectal, genital, oropharyngeal, serological, and dermatological specimens, respectively, were subjected to PCR analysis.

Among the specimens, 17% (n=184) were found to be MPXV-positive, 77% (n=142) of which, had Ct values ≥34, often without any MPX symptoms. At follow-up, 66% (12 of 18) of sexual and 14% (one of seven) of non-sexual contacts were PCR-diagnosed as MPXV-positive, of whom, five showed low viral loads and lacked the usual symptoms of MPX. In 83% (five out of six) individuals experiencing typical MPX symptoms, MPXV deoxyribonucleic acid (DNA) was detected four days (n=2) and one (n=3) days before symptom onset in one, two, four, and three oropharyngeal, saliva, anorectal, and genital specimens, respectively.

In 75% (n=3) anorectal specimens, MPXV could not be cultured in the pre-symptomatic period. Among three individuals, replication-competent MPXV was detected. The highly specific and highly sensitive PCR cut-offs were determined as those with Ct values of 34 and 37, respectively. Among the specimens, 8.0%, 3.0%, and 1.0% of anorectal, saliva, and genital specimens had Ct values below 34, respectively. Among the sexual contacts, 67% (12 out of 18) were probably infected (n=4) or infected (n=8). Contrastingly, only 14% (one of seven individuals) of non-sexual contacts were probably infected, and definite MPX was detected in none of them.

Serology for orthopoxviruses verified the participants’ outcome in 48% (12 out of 25) cases, could not be interpreted in 40% (10 out of 25) cases, and contradicted the PCR reports in 12% (three out of 25) cases. Among individuals with definite MPXV infections, 75% (n=6) of them experienced typical MPXV infection symptoms, 13% (n=1) developed fever only, and 13% (n-1) developed fatigue only. Typical MPX symptoms such as cutaneous rash, proctitis, and tonsillitis developed in four, two, and two individuals and were heralded by prodromal symptoms among all the individuals.

No probably infected case individuals experienced typical MPXV infection symptoms. Two individuals did not develop any symptoms, one experienced night sweats only, and two developed other symptoms such as headaches and painful throat lacking tonsillitis. Two and five definitely infected and probably infected individuals, respectively, who lacked typical MPXV infection symptoms showed significantly lesser viral loads than those with typical MPX symptoms (medians for least Ct values 17 vs. 35). More MPXV-positive individuals lacking typical MPX symptoms had received smallpox vaccinations during childhood (two out of seven) or PEV (three out of seven) than those experiencing typical MPX symptoms.

Overall, the study findings highlighted the elevated risk of MPXV transmission during sexual intercourse and confirmed the nature of pre-symptomatic MPXV shedding. Therefore, sexual contact with MPXV-positive partners must be refrained from regardless of MPX symptoms.

*Important notice

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.

Journal reference:
Pooja Toshniwal Paharia

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Pooja Toshniwal Paharia

Dr. based clinical-radiological diagnosis and management of oral lesions and conditions and associated maxillofacial disorders.

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