Case Report: Recurrent Mpox in a Healthcare Worker in Nigeria

ABSTRACT.

We report the first case of recurrent Mpox from Africa. The patient is a 36-year-old, previously healthy, HIV-negative male healthcare worker who developed two episodes of laboratory-confirmed Mpox in 2017 and 2018, 9 months apart. In both cases, he had prior close contact with confirmed Mpox cases in the hospital setting. On follow-up in 2022, he also reported recurrent postcoital skin eruptions over a previously healed genital scar from the first episode of Mpox. We highlight the need for future studies to investigate the true burden and risk factors for Mpox reinfection, relapse, and recrudescence.

INTRODUCTION

Mpox and smallpox viruses belong to the Orthopoxvirus genus of poxviruses,¹ and because survivors of smallpox infection are generally known to develop lifelong protection against reinfection,^2,3 it was presumed that, like smallpox, natural Mpox infection could lead to prolonged or lifelong protection against reinfection. However, emerging case reports of persons with recurrent symptoms of Mpox are casting doubt on this proposition.

In a review of seven cases of Mpox managed in the United Kingdom in 2019, Adler and colleagues⁴ reported a case of recurrence of symptoms of Mpox in a Nigerian man 6 weeks after an initial recovery. During the 2022 Mpox outbreak, Raccagni and colleagues⁵ reported a case of Mpox of the eye that persisted for 8 months. Between January and May 2023, six countries in Europe have reported recurrent Mpox in eight apparently healthy men who have sex with men 1–6 months after their initial infection, including in an individual who had completed the recommended two doses of the modified vaccinia Ankara smallpox vaccine.^6–11 These case reports of recurrent or persistent Mpox have generated debate on the potential of Mpox resurgence in individuals and communities due to reinfection (infection by a new viral strain), relapse (reactivation of a previously latent infection from a sanctuary site), or recrudescence (reappearance of symptoms and virus in circulation due to failure to clear the virus after the initial infection).

There has been no prior report of Mpox recurrence from Africa. In this paper, we report a case of recurrent Mpox in a healthcare worker (HCW) diagnosed during the 2017–2018 Mpox outbreak in Nigeria.

CASE REPORT

First episode of Mpox.

On November 14, 2017, a 30-year-old male HCW developed fever, headache, myalgia, and malaise followed 3 days later by sore throat and pruritic maculopapular rashes first observed on his back. Over a few days, similar rashes appeared on other parts of the trunk, upper limbs, scalp, soles, palms, tongue, groin, penile skin, and perianal area (Figure 1A). The rashes were discrete, monomorphic, and centrifugal in distribution, less than 0.5 cm in size, evolving from maculopapular to vesiculopustular lesions over a period of 3–5 days. Overall, 25 lesions were noted, as well as associated submental and inguinal lymphadenopathy. He received analgesics, antimalarials, amoxyl/clavulinic acid, and antipruritic drugs. He did not receive any antiviral. All symptoms resolved and skin lesions crusted and healed 14 days after the initial symptoms.

Figure 1.

Clinical lesions in a case of recurrent human Mpox. (A) The white arrow points to maculopapular lesions on the palm (first episode). (B) The white arrow points to an ulcerated inguinal rash (second episode). The black arrow points to a healed scar on the base of the penile shaft after the first episode of Mpox. (C) The white arrow points to vesiculopustular lesions on the base of the penile shaft, which is over a previous Mpox-related healed scar from the first episode. The patient provided informed consent for publication, including publication of clinical images.

This HCW had been actively involved in the management of confirmed Mpox patients hospitalized in a tertiary hospital in Nigeria from September to November 2017. His last clinical contact with a confirmed case of Mpox was 1 week prior to the onset of the first set of symptoms. According to his own account, he observed the recommended practices for use of full personal protective equipment (PPE) during all patient care.

He had chicken pox in 2004, did not receive a childhood smallpox vaccine, and had no history of close contact with wild animals or bush meat consumption a month prior to the onset of symptoms. He is a self-reported heterosexual and did not report any sexual activity a month prior to his illness.

The patient met the criteria for laboratory-confirmed Mpox as previously described.¹² A lesion swab tested positive for Mpox viral DNA by real-time polymerase chain reaction (PCR) by the TaqMan method with a cycle threshold (CT) value of 17.52. Serum Orthopoxvirus-specific IgM and IgG antibodies were positive by ELISA (0.59 and 0.19 optical densities, respectively) as previously described.¹³ Subsequent genomic sequencing of stored samples was not possible as a result of poor sample quality. However, clade IIb was the circulating strain at the time of his illness.¹⁴ Concomitant chicken pox infection was also excluded by PCR. HIV serology was negative.

Second episode of Mpox.

On August 14, 2018, 5 days after entering the room of a confirmed case of Mpox without donning PPE and 9 months after the first episode of Mpox, the patient observed a painless left inguinal vesiculopustular skin rash about 0.5 cm in size. This lesion later increased in size and ulcerated and was associated with bilateral inguinal lymphadenopathy (Figure 1B). Five days after the onset of the inguinal rash, he developed an intermittent high-grade fever with chills and rigors, sore throat, malaise, and generalized body weakness. On the date of the onset of fever, he also noticed vesiculopustular skin eruptions that started on the right foot and rapidly spread to affect the soles, palms, face, trunk, groin, and scalp. Overall, there were about 18–20 skin lesions. No rash developed on the penile skin and anogenital area, and the sites of skin lesion were distinct from the first episode of Mpox. Lesions were not painful and were said to be less pruritic than in the first episode. He was treated with analgesics, antibiotics, and antipruritic drugs. He did not receive any antiviral. All symptoms resolved, and the skin lesions healed 17 days after the onset of the inguinal rash.

Lesion swab and crust samples from this second episode also tested positive for Mpox by PCR (CT value, 18.3). Genomic sequencing suggested a clade IIb strain infection (GenBank accession number MT903341). Serum samples were not available for additional serological diagnosis. Except for thrombocytopenia (90,000 cells/μL), other laboratory results including full blood counts, random glucose tests, liver function tests, and renal function tests were normal. He was seronegative for HIV, hepatitis B and C, and syphilis (by venereal disease research laboratory test). Lesion swab PCR was negative for varicella zoster infection. His CD4 count by flow cytometry was 505 cells/μL. Abdominal ultrasound revealed mild hepatomegaly with normal liver architecture.

He did not engage in any sexual activity a month prior to his illness. He was not taking any medication and had no history of concomitant chronic diseases, including immunosuppressive conditions, before any of the episodes of Mpox. No clinical sequelae, including eye or neurological sequelae, were observed after both episodes of Mpox.

Follow-up in 2020–2022.

After a recent enquiry on his health status undertaken in November 2022, the patient volunteered past histories of recurrent self-limiting skin eruptions first observed in April 2020, about 3 months after his marriage. By his account, 1–2 days after prolonged and repeated vaginal sexual activity with his wife, he usually developed slightly pruritic but painless vesiculopustular lesions on the base of his penile shaft specifically over previously healed scars from the first episode of Mpox. These skin eruptions, which occurred twice in 2020, thrice in 2021, and twice in 2022, were not associated with fever, body pains, or any other systemic symptoms, and always healed spontaneously within a week without the need for any medication. The last episode was in October 2022 (Figure 1C). His wife remained asymptomatic. Unfortunately, because this history was obtained retrospectively, lesion samples were not available for further laboratory investigation.

DISCUSSION

To the best of our knowledge, this is the first report of recurrent Mpox from an Mpox-endemic country in Africa.

Because viral genomic sequencing was not available from the first episode to allow for comparisons, we could not confirm infection by a new strain of virus that is indicative of an Mpox reinfection. However, the occurrence of clinical and laboratory features of Mpox 9 months after the first episode of the disease in our case is more likely suggestive of an Mpox reinfection than a relapse or recrudescence. Only one of the eight cases of possible Mpox reinfection reported in the literature had genomic sequencing results from the two episodes confirming a reinfection by different viral strains.⁹ Recurrence of viral infections could be due to several factors, including viral latency and subsequent reactivation, either the lack of or short-lived postinfectious protective immunity, infection by new pathogenic strains, and host-related susceptibility factors.^15–17 How and whether these risk factors predispose to Mpox recurrence are not known and deserve further studies.

The clinical presentation during the first episode of Mpox in our case was comparable to other confirmed cases reported during the 2017 Nigeria Mpox outbreak.^12,18 However, the second episode presented atypically, with an inguinal rash as the first symptom followed days later by fever and secondary skin eruptions on other parts of the body. This presentation seemed typical of inoculation-related infection as described for smallpox.¹⁹ However, it is not clear how inoculation could have occurred in this case to result in a primary lesion in the inguinal area. Although healthcare-associated exposures were suspected for both episodes of infection, it was impossible to ascertain the exact mode of transmission from the patient’s clinical history.

Our case reported recurrent skin eruptions over healed scars usually after prolonged sexual activity. A case of Mpox recurrence reported in 2019 in the United Kingdom also followed sexual activity, but the authors did not compare lesion characteristics between the two episodes.⁴ In herpesvirus infections, relapse and recurrent infections are known to occur when latent viruses in sensory neurons and epithelial cells are reactivated by local trauma or a systemic stressor.¹⁷ Because laboratory testing of these recurrent lesions was not possible in our patient, we cannot tell whether the postcoital-related recurrent skin eruptions are due to herpesvirus-related genital infection, recurrent relapse of Mpox, or something different. Follow-up is ongoing to investigate any future recurrence.

Our patient was a previously healthy, HIV-negative young man who had no concomitant chronic diseases, including immunosuppressive conditions, that could have made him susceptible to recurrent Mpox. Although we did not have serological results during the second episode for comparison, it is not unusual for some individuals to have suboptimal immune responses to certain infections influenced by several host factors, which we did not investigate in our study.^2,20,21

Overall, our case report of recurrent Mpox and similar cases reported in Europe suggest that protective immunity after natural Mpox infection is not lifelong in some individuals. Our case draws attention to the potential of HCWs to become reinfected with Mpox in the hospital setting without appropriate PPE and calls for future prospective studies to clarify the true burden and risk factors for Mpox reinfection, relapse, and recrudescence.