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A case of mpox reinfection
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Clinical Infectious Diseases 11 March 2023
A healthy young man first diagnosed with mpox in May 2022 presented again in November 2022 with anal proctitis and a positive PCR on a rectal swab for MPX virus (MPXV) after a recent trip to Brazil, where he engaged in condomless sexual intercourse with multiple male partners.
A 31-year-old man in good general health presented in May 2022 with four umbilicated lesions on the penis. He was on pre-exposure prophylaxis (PrEP) for HIV and reported having had condomless sex with men, including receptive anal intercourse. He did not report previous smallpox infection or vaccination. On physical exam, no lymphadenopathy was found, and oropharyngeal and anal inspection was normal. The patient did not report fever or any other symptoms. Skin lesions and pharyngeal swabs tested positive for MPXV by real-time orthopoxvirus PCR5 with a cycle threshold (Ct) of 16.5 and 35.3, respectively. He was also diagnosed with asymptomatic urinary Chlamydia trachomatis infection. Within two weeks, skin lesions spontaneously resolved without complications.
On 1 December 2022, the patient reported persistent perianal pain without bleeding nor discharge. Symptoms had started two weeks before, on his return from Brazil in November 2022, where he had engaged in condomless anal intercourse with multiple male partners. No other complaints or symptoms were reported. He related a last receptive anal intercourse two weeks before the presentation. The patient did not recall any signs or symptoms of mpox among his partners, nor was he aware of an MPXV infection among them. Clinical examination found no skin lesion in the perianal region or other body parts. Apart from a slightly palpable painless right inguinal lymphadenopathy, the medical examination was normal. Four weeks after symptom onset, a proctologic examination revealed a small anal fissure but no typical mpox lesion Sexually transmitted infectious diseases were screened using standard diagnostic tests. The anal swab done on 1 December came back positive for MPXV with a Ct of 27 and for Chlamydia trachomatis (non LGV). The latter was treated with a 7-day course of doxycycline. HIV serology and viremia were negative, syphilis serology negative for acute infection. On 13 December 2022, rectal and pharyngeal swabs were collected again and turned out negative. Orthopoxvirus PCR was also negative in the blood and urine on 13 December 2022. Total mpox antibodies were tested (Custom Monkeypox Human ELISA Kit, RayVio, Georgia, USA) on sera collected prior to the first episode in May 2022 and after the second in December 2022: they came back negative and positive, respectively. Unfortunately, no serum had been collected between the two episodes.
While the next few months will be decisive in determining whether this case is an exception or the first of a beginning series, it is crucial to raise awareness among clinicians that MPXV may not develop effective protection in time and that if suspicion criteria are met, patients should be tested again for MPXV. With the growing evidence for asymptomatic and/or prolonged shedding of MPXV, screening among naïve, recovered and vaccinated individuals also needs to be addressed. Meanwhile, public health authorities should be informed and prepare for the consequences increasing mpox reinfections would imply for the management of the current mpox epidemic. Further tools may be useful, such as the development of specific mpox vaccines.
Case of apparent mpox reinfection

We present an apparent second episode of mpox (monkeypox) genital ulcerative disease in a non-immunosuppressed MSM (man who has sex with men) patient who had completely recovered from a primary mpox infection 4 months previously. The patient had also received a complete two-dose course of smallpox vaccination between the two presentations. This case highlights the importance of continuing to include mpox in the differential diagnoses for individuals presenting with genital or mucosal ulceration, regardless of assumed immunity derived from prior infection or vaccination.
A white man in his early 30s presented in July 2022 to a sexual health clinic in South West England with a recent history of inguinal lymphadenopathy, rectal discharge and rectal pain. Examination revealed obvious rectal discharge only and no external or mucosal skin lesions. He was treated empirically for proctitis with 2 weeks of doxycycline and 1 week of aciclovir. A rectal swab taken on this occasion tested positive for mpox, and he was given routine isolation advice, making an uncomplicated recovery within 2 weeks. He received two doses of Jynneos smallpox vaccination as part of the nation-wide programme—the first dose given subcutaneously 1 week after this presentation and the second dose given subcutaneously 10 weeks after that. In November 2022, he re-presented with a 3-day history of headache, backache and neck pain. He had no focal neurological signs on examination. There was a 2 mm aphthous ulcer on his right lower gum and a 1 mm ulcer 2 cm within the anal canal as well as tender left-sided raised cervical lymph nodes. He reported numerous casual male sexual partners over the preceding 2 weeks. The anal ulcer tested positive for mpox, and again he had an uncomplicated recovery within 2 weeks. Significant medical history included a diagnosis of neurosyphilis associated with syphilis seroconversion the previous year, for which he had completed a treatment course. The patient had, in the past, been treated for rectal Chlamydia trachomatis and Neisseria gonorrhoeae infections. He had no other comorbidity and took PrEP (HIV pre-exposure prophylaxis) only with no other prescribed or recreational drugs.
As far as we are aware, there have not been any other published cases of reinfection during the 2022 mpox outbreak. An alternative explanation to reinfection is that mpox infection persisted following first infection during the intervening period. This is unlikely to explain the new clinical signs and prodromal illness the patient experienced at the second presentation, which could not be attributed to any other investigated STI. Persistence is also unlikely, given that time from infection to viral clearance is typically less than 6 weeks6 and the repeat rectal swab 2 weeks after the second presentation was negative for mpox. Nucleotide sequence comparison of mpox DNA detected in both clinical episodes and additional tests between episodes would be required to shed further light on this. Meanwhile, this case informs the advice health professionals give to patients about mpox and clearly indicates including mpox infection in the differential for patients presenting with mucocutaneous lesions, regardless of prior infection or vaccination status.

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