Letters16 August 2022

Detection of Monkeypox Virus in Anorectal Swabs From Asymptomatic Men Who Have Sex With Men in a Sexually Transmitted Infection Screening Program in Paris, France

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    Background: A monkeypox virus (MPXV) outbreak emerged in May 2022, affecting mostly men who have sex with men (MSM). Although most infections were characterized by cutaneous lesions, a recent report described 3 asymptomatic men with no cutaneous lesions but with positive results on anorectal MPXV polymerase chain reaction (PCR) testing (1). Determining whether MPXV infection can be asymptomatic may better inform epidemic management.

    Objective: To assess the presence of MPXV in anorectal samples among asymptomatic MSM routinely tested for bacterial sexually transmitted infections (2).

    Methods and Findings: We retrospectively performed testing for MPXV on all anorectal swabs that were collected in our center as part of a screening program for Neisseria gonorrhoeae and Chlamydia trachomatis. Per French guidelines, this screening is performed every 3 months among MSM with multiple sexual partners who are either taking HIV preexposure prophylaxis (PrEP) or living with HIV and receiving antiretroviral treatment (2). Patients could have urine samples and anal swabs collected at our clinic or a private laboratory. After the first case of MPXV infection was identified in France on 19 May 2022, screening was halted in patients who had lesions suspicious for MPXV (3). We report on asymptomatic MSM who tested negative for N gonorrhoeae and C trachomatis on MPXV anal swabs collected at the Infectious Disease Department and the Sexual Health Clinic of Bichat-Claude Bernard Hospital in Paris, France, from 5 June to 11 July 2022. All participants attended a clinical visit on the day of sampling as part of routine PrEP or HIV treatment follow-up. Participants gave written informed consent to have their data recorded in Nadis (www.dataids.org; Fedialis Medica, CNIL number 1171457 [24 May 2006]), an electronic medical record designed for follow-up of persons living with HIV or receiving HIV PrEP and use of their data for research. The local review board did not require specific consent to use remnant routine biological samples in the setting of the MPXV epidemic.

    After heat inactivation (12 minutes at 70 °C), nucleic acids were extracted using a STARMag 96 X 4 Universal Cartridge Kit (Seegene) on the MICROLAB NIMBUS system (Seegene). MPXV-specific PCR was performed using a previously published protocol (4).

    During the study period, 706 MSM visited our clinic, 383 had symptoms suggestive of MPXV infection (40% had anal lesions), and MPXV infection was confirmed in 271 of those with symptoms (Table). Screening for C trachomatis and N gonorrhoeae infection was not performed when MPXV infection was suspected because of laboratory biosafety restrictions (5). Of the 706 MSM, 323 had no MPXV symptoms, and 213 had anal swabs collected and were negative for C trachomatis and N gonorrhoeae (Table). Among these 213 MSM, the median age was 38 years (IQR, 29 to 48 years), and 110 (52%) were living with HIV and receiving antiretroviral therapy, with a median of 9 years (IQR, 4 to 18 years) since diagnosis. Among those with HIV, 78% had undetectable viral load (median viral load was 74 copies/mL [IQR, 37 to 2270 copies/mL] in the others), and the median last CD4 T-cell count was 0.766 × 109 cells/L (IQR, 0.560 to 1.001 × 109 cells/L).

    Table. Screening for Sexually Transmitted Infections and MPXV Infection in 706 MSM Visiting the Sexual Health Clinic Between 5 June and 11 July 2022


    MPXV PCR was successfully performed on 200 of 213 anal swabs and was positive in 13 (6.5%). Of those testing positive, 8 were living with HIV; all had undetectable HIV-1 viral load, and all had a CD4 T-cell count above 0.500 × 109 cells/L, except 1 who had a CD4 T-cell count of 0.123 × 109 cells/L. We contacted all 13 MPXV-positive participants who were initially asymptomatic to assess symptom status and advised them to limit sexual activity for 21 days after the test date and to notify their recent sexual partners. None reported symptoms suggestive of MPXV infection, but 2 subsequently presented to our clinic with symptoms. One had a cycle threshold (Ct) value of 20.7 on PCR of the sample taken during the asymptomatic stage and a Ct value of 33.0 seven days later, when he presented with anal rash. The other presented with pharyngitis and fever but no anal symptoms; PCR on the anal swab taken during the asymptomatic phase showed a Ct value of 38.2, and PCR on a pharyngeal swab 9 days later showed a Ct value of 24.

    Of the 187 asymptomatic participants who tested negative for MPXV, 3 presented to our clinic more than 3 weeks after the initial MPXV-negative anal swab with symptoms suggestive of MPXV infection and tested positive.

    Discussion: This report documents positive MPXV PCR results from anal samples in asymptomatic MSM. Whether this indicates viral shedding that can lead to transmission is unknown. If so, the practice of ring postexposure vaccination around symptomatic persons with probable or confirmed MPXV infection may not be sufficient to contain spread. Recent French recommendations have advised vaccination for all MSM with multiple partners (5).



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    Aaron Shengting Mai; Eng-King Tan19 August 2022
    Asymptomatic Monkeypox Infection

    Ferré and colleagues provided important insights into asymptomatic infection with monkeypox (MPX) amongst men who have sex with men (MSM). They presented 13 asymptomatic patients who tested positive for the MPX virus (MPXV) (1.84%, 13/703 patients).

    It would be useful to know the age of the asymptomatic MPX patients and whether those with and without MPX had received prior smallpox vaccination. This information will help stratify potential at-risk asymptomatic individuals for further screening.

    There is also a lack of a control group (general population or another non-MSM cohort) for comparison. This is relevant because, amongst the 13 cases identified, eight were living with HIV and had undetectable viral loads. Prevalent infection within MSM may perhaps partially account for the lack of symptoms in these patients, as well as the insidious spread of MPX in this community. It is unclear if the asymptomatic carrier rate is higher in MSM compared to other healthy or diseased groups, and if it is the case, how prior HIV infection affects the clinical manifestation or immune response. 

    The risk of spread among asymptomatic carriers is of particular concern, but until a cheap, fast, and reliable diagnostic test is available for screening, contact tracing as well as isolation of cases and close contacts alone may not be enough. A cost-effective, convenient, and self-administered test kit can potentially protect patient privacy, especially given the stigma surrounding the MSM community. This is evidenced by the implementation of self-administered test kits for COVID-19.

    More robust epidemiologic data are needed regarding the prevalence, associated clinical features and mode of spread in asymptomatic cases in the general population and in those with chronic medical diseases and compromised immunity. The potential for asymptomatic spread of MPX is unlikely restricted to the MSM community.

    Shu Yuan, Si-Cong Jiang, Zi-Lin Li3 October 2022
    Asymptomatic monkeypox infection implies a low inoculating dose

    We read with interest Ferré and colleagues' research letter (1) about detection of monkeypox virus (MPXV) in anorectal swabs from asymptomatic men who have sex with men (MSM). Among 200 participants who were subjected to MPXV PCR tests, the authors reported 13 MPXV-positive participants who were initially asymptomatic (two of them showed mild symptoms 7–9 days later) (1).

    The severity of symptoms is usually correlated with the initially inoculating dose. The presence of a large number of asymptomatic or mild-symptomatic persons imply that they may not direct contact with anogenital lesions, where the viral loads are the highest (2). Actually, monkeypox patients with apparent genital or rectal lesions (showing rectal pain and penile swelling firstly) are unlikely to be engaged in high-risk sexual behaviors, but seek medical advice instead.

    However, MSM are prone to have condomless sexual intercourse and leave the seminal fluid inside the body. A clinical study reported positive MPXV results in the seminal fluid obtained from monkeypox patients at the time closest (5–7 days) to symptoms onset with a Ct range from 27–30; while the Ct values of genital or rectal lesion swabs were about 15–18 (2). Though in a low viral load, seminal MPXV may be still infectable. Alternatively, seminal MPXV may get into the blood stream directly, if anal bleeding occurs, especially when haemorrhoids are present.

    Before this year, monkey pox was not known as a sexually transmitted disease. Recent epidemiological data indicated that most monkeypox patients were MSM and 36%–41% of them had concomitant HIV infections (3,4). MSM usually adopt HIV pre-exposure prophylaxis (PrEP) (3). However, use of PrEP may be a risk factor for MPXV infection, because that MSM with PrEP do not often use condoms (5). WHO recommended PrEP since 2015. Thus, the current correlation between sexual behaviors and MPXV infections might be explained.

    Ferré et al. (1) reported positive MPXV PCR results from anal samples in asymptomatic MSM. However, this did not indicate an effective viral shedding that can lead to transmission. Asymptomatic patients do not develop rashes or skin lesions, and therefore are believed to be of little or no epidemiologic importance. Nevertheless, Ferré et al. found a high viral load in a patient during the asymptomatic stage with Ct value of 20.7 (1). Whether a high viral load in seminal fluid obtained from asymptomatic MSM could be detected needs further investigations.


    1. Ferré VM, Bachelard A, Zaidi M, et al. Detection of monkeypox virus in anorectal swabs from asymptomatic men who have sex with men in a sexually transmitted infection screening program in Paris, France. Ann Intern Med. 2022;Online ahead of print. [PMID: 35969863] doi:10.7326/M22-2183
    2. Antinori A, Mazzotta V, Vita S, et al. Epidemiological, clinical and virological characteristics of four cases of monkeypox support transmission through sexual contact, Italy, May 2022. Euro Surveill. 2022;27:2200421. [PMID: 35656836] doi:10.2807/1560-7917.ES.2022.27.22.2200421
    3. Thornhill JP, Barkati S, Walmsley S, et al. Monkeypox virus infection in humans across 16 countries - April-June 2022. N Engl J Med. 2022;387:679-91. [PMID: 35866746] doi:10.1056/NEJMoa2207323
    4. Patel A, Bilinska J, Tam JCH, et al. Clinical features and novel presentations of human monkeypox in a central London centre during the 2022 outbreak: descriptive case series. BMJ 2022;378:e072410. [PMID: 35902115] doi:10.1136/bmj-2022-072410
    5. Torster L, Tegtmeyer J, Kött J, Christolouka M, Schneider SW. Localized monkeypox infestation in MSM on pre-exposure prophylaxis. J Eur Acad Dermatol Venereol. 2022;Online ahead of print. [PMID: 35993154] doi:10.1111/jdv.18539