Suspected case of monkeypox reinfection versus reactivation in a immunocompetent patient,Barcelona,2022

Introduction

Since the start of the Monkeypox (Mpox) outbreak and as of 31 January 2023, 85,469 confirmed cases have been reported. ¹ Since 20 May 2022, 213 Mpox infections have been diagnosed in our Sexually Transmitted Infections’ (STI) clinic. We present a case of possible Mpox reinfection versus reactivation.

Case

A 51 year-old man who has sex with men, without chronic diseases or concomitant medication except for daily pre-exposure prophylaxis against HIV, vaccinated against smallpox in his childhood, attended our clinic on 27 July 2022. He was complainig of three Mpox typical pseudo-pustules on the pubis and the base of the penis, and groin lymphadenopathy of four days’ duration (Figure 1(a)), without other symptoms. Real-time polymerase chain reaction (RT-PCR) was performed on a lesion with positive result for Mpox, 16.82CT (Cycle Threshold, LightMix Modular Monkeypox Virus, Roche). The patient was managed conservatively, and the genital wounds healed after three weeks without complications.OPEN IN VIEWER

On 28 October 2022, (Figure 2) he attended the emergency room with a two day history of a genital lesion and painful lymphadenopathy in the right groin (Figure 1(b)). Ulcerative STI and Mpox RT-PCR were negative. He was recommended watchful waiting.OPEN IN VIEWER

On 15 November 2022, he reconsulted due to the persistence of the lesions. Physical examination showed an indurated ulcer near to the coronal sulcus and other smaller pseudo-papules in glans, frenulum and the skin of the penis and right groin lymphadenopathy (Figure 1(c)). He reported ten different casual sexual partners in the preceding three months and last unprotected sexual intercourse ten days before clinical presentation. He denied contact with Mpox confirmed or suspected case, pets, recent international travel, attending mass events or chemsex. Immediate dark field microscopy from the biggest sore was positive for spirochetes, and the patient was treated for presumptive primary syphilis with 2.4 million units of benzathine penicillin intramuscularly. RT-PCR was subsequently reported as positive for bothTreponema pallidum and Monkeypox (39CT). Due to the low viral load for monkeypox whole genome sequencing could not be performed. Rapid Plasma Reagin (RPR) was positive 1/16 (last syphilis test in September 2022 with positive EIA and TPHA and negative RPR from a previous treated syphilis) and HIV serology was negative. After four weeks the patient was fully recovered.

Discussion

Whether our patient presented Mpox reinfection or reactivation remains unknown. Current recommendations for prevention of Mpox exclude those already vaccinated in childhood. Early studies reported that vaccinated individuals were 85% less likely to contract Mpox and severe complications ² and long-term effects of the infection were less common (39.5% vs 74%). ³ Studies from this recent outbreak reported 9–18% vaccinated participants.^4,5 Smallpox Vaccinia virus-based (VACV) vaccines induce cross-protection against symptoms caused by other orthopoxviruses, including Mpox,^6–10 but vaccination at childhood does not necessarily provide robust neither permanent immunity against Mpox ¹¹ as is suggested in our patient. Specific memory CD4⁺ and CD8⁺ T cells, B cells and antibodies were found to persist >50 years following VACV vaccine. However, only half of individuals present protective antibody titers >20 years after vaccination.^12–14

Smallpox and Mpox infections are believed to generate permanent immunity. Our patient had Mpox three months ago, suggesting that milder/localized infections may not generate an immune response as strong as smallpox used to. The second episode occurred during a very low incidence period (Figure 2). A similar case of suspected Mpox reinfection was recently published. ¹⁵ If we consider them a reinfection, it opens the possibility of unrevealed virus circulation due to asymptomatic infections in the context of a population with currently high immunization rates due to natural or vaccine-acquired immunity. This should be taken into account due to the risk of resurgent/new outbreaks and the current exclusion of patients who already had Mpox infection in the general pre-exposure vaccine recommendations.

According to the reactivation hypothesis, there are scarce data about the frequency and duration of DNA shedding and viable virus in each location and fluids and its contribution to transmission. Previous studies^16–19 have reported positive RT-PCR in different samples up to 2–3 weeks after the symptoms’ onset. A recent series showed for 90% cases 41 days from symptom onset to viral clearance in skin lesions and 39 days in semen. ²⁰ Also, a small series reported two cases of longer viral shedding in immunocompetent patients. ²¹ In our case, the broken skin barrier due to another STI could have allowed DNA detection, suggesting a genital/skin reservoir of Mpox. Nevertheless, the low viral load (39 CT) detected in the second episode could be explained for the delay between the onset of the lesions and the sample collection; and DNA was detected in new and differently located genital wounds, three months after first Mpox, with no immunosuppressive condition. Whether this patient is infectious remains unknown, as secondary transmission could not be evaluated.

This could be the second reported case of reinfection versus reactivation of Mpox in a healthy and previously vaccinated patient. Screening of asymptomatic subjects with high-risk exposure may be considered, as well as increase awareness of reinfection if new symptoms arise after first episode’s resolution. Prospective monitoring in time of patients would give us information about the possibility of reactivation or long-term effects.

Limitations to this report include lack of acquiring phylogenetic comparison with first episode due to impossibility of performing whole genome sequencing, delay in the sample collection and no identification of secondary cases.