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Asymptomatic Monkeypox Reported
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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.
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).
MPXV PCR was successfully performed on 200 of 213 anal swabs and was positive in 13 (6.5%)
"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 monkeypox virus infection may not be sufficient to contain spread," they wrote in the Annals of Internal Medicine.
In conclusion, the finding of several monkeypox cases that remained undiagnosed at the beginning of the epidemic implies case finding should be intensified. First, healthcare workers and individuals at risk of infection should be aware that monkeypox symptoms may overlap with those of other diseases, in particular STIs. Second, not all individuals with monkeypox infection notice symptoms, and so may not seek medical attention. Increased awareness of the sometimes subtle signs of disease, as well as intensified testing and contact tracing, may be helpful to diagnose additional cases. Populations at risk of infection should be encouraged to keep record of their close contacts and, until there is more clarity about the extent to which asymptomatic individuals are contagious, high-risk contacts of infected cases should be aware that they might transmit the virus even if asymptomatic.
Brief Communication
Published: 12 August 2022
Retrospective detection of asymptomatic monkeypox virus infections among male sexual health clinic attendees in Belgium
Abstract
The magnitude of the 2022 multi-country monkeypox virus outbreak has surpassed any preceding outbreak. It is unclear whether asymptomatic or otherwise undiagnosed infections are fuelling this epidemic. We aimed to assess whether undiagnosed infections occurred among men attending a Belgian sexual health clinic in May 2022. We retrospectively screened 224 samples collected for gonorrhoea and chlamydia testing using a monkeypox virus (MPXV) PCR assay, and identified MPXV DNA-positive samples from four men. At the time of sampling, one man had a painful rash, and three men had reported no symptoms. Upon clinical examination 21 to 37 days later, these three men were free of clinical signs and they reported not having experienced any symptoms. Serology confirmed MPXV exposure in all three men, and MPXV was cultured from two cases. These findings show that certain cases of monkeypox remain undiagnosed, and suggest that testing and quarantining of individuals reporting symptoms may not suffice to contain the outbreak.
To summarise, we found four monkeypox cases that had remained undiagnosed among men consulting for gonorrhoea/chlamydia testing in May 2022. Besides one unrecognised symptomatic case, these included three men who had not noticed any symptoms. Interestingly, case 1 predated the first detected symptomatic case in Belgium by several days, and could not be epidemiologically linked to any other monkeypox case through contact tracing, nor did he re port international travel or participation in mass gatherings before day 0, indicating that MPXV had been circulating in Belgium before the first cases were formally detected. While it cannot be excluded that those three asymptomatic men had unnoticed signs of monkeypox at the time of infection, the significance of these cases lies in the fact that they would not have sought medical care if it were not for a scheduled visit for routine HIV follow-up and STI screening. Indeed, as they were not aware of their MPXV infection, none of the men had self-isolated and all of them had sexual contacts around the time of detectable MPXV DNA. The presence of replication-competent virus in two out of three asymptomatic cases indicates that they may have been able to transmit the virus, but the possibility of onward transmission could not be verified by the retrospective nature of our study.
While other retrospective studies have found serological evidence of MPXV infection in asymptomatic MPXV-exposed individuals, 15–21 our study adds the finding of replication-competent virus particles in asymptomatic.
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Asymptomatic Monkeypox Virus Infections Among Male Sexual Health Clinic Attendees in Belgium
16 Pages Posted: 21 Jun 2022
Interpretation The 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. https://www.medrxiv.org/content/10.1101/2022.07.04.22277226v1
The three asymptomatic monkeypox cases were men between 30 and 50 years old, each with a well-
controlled HIV infection and a history of multiple STIs. None of them were vaccinated against smallpox.
The three asymptomatic men were recalled to the clinic for further investigation within 21 to 37 days
after the initial sampling. At that time, none of the men showed signs or symptoms of monkeypox and
all denied having noticed any symptoms during the two months prior or 3 weeks after initial sampling.
All three men had condomless sexual intercourse with at least one male partner within a few days to
one month before sampling. Two out of three men had sexual contacts while travelling abroad within
two weeks before sampling. As far as traceable, none of their partners have reported signs or symptoms of monkeypox. Results of basic laboratory investigations at the time of sampling, including renal and liver function tests, as well as C-reactive protein were normal. Follow-up anorectal swab samples tested PCR negative for MPXV (Table 1).
Interestingly, one of the asymptomatic
men in our study predates the first detected symptomatic case in Belgium by several days,20 and could not be epidemiologically linked to any other monkeypox case, nor did he report international travel or participation in mass gatherings. This may indicate that MPXV circulated among asymptomatic individuals in Belgium before the outbreak was detected
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16 August 2022 Annals of Internal Medicine
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.
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).
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 X 109 cells/L, except 1 who had a CD4 T-cell count of 0.123 X 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.
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 X 109 cells/L (IQR, 0.560 to 1.001 X 109 cells/L).
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
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 X 109 cells/L (IQR, 0.560 to 1.001 X 109 cells/L).
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 X 109 cells/L, except 1 who had a CD4 T-cell count of 0.123 X 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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