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11 June 2023: Articles  USA

The Reemerging Condition of Vaccinia: A Case Report and Brief Review of Monkeypox and Vaccinia Vaccines

Challenging differential diagnosis, Unusual or unexpected effect of treatment, Diagnostic / therapeutic accidents, Unexpected drug reaction, Rare disease

Christian Ryckeley ORCID logo1ABF, Glenn Goodwin ORCID logo1ABDEF*, Alexandra Alvarez-Calderon1ADE

DOI: 10.12659/AJCR.941006

Am J Case Rep 2023; 24:e941006

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Abstract

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BACKGROUND: The emergence of the monkeypox virus (mpox) is causing a large-scale re-administration of vaccinia-based vaccines. Many physicians have not been exposed to the rare, but implicit, complications, revealing a glaring need for updated evidence and re-examination. We present a case of a Human Immunodeficiency Virus (HIV)-positive male patient who presented to the Emergency Department (ED) with vaccinia symptoms several days after receiving the JYNNEOS vaccine.

CASE REPORT: A 45-year-old man with a past medical history of well-controlled HIV presented to the ED for 5 days of nocturnal diaphoresis, chills, intermittent arthralgia, and myalgia that began shortly after receiving the JYNNEOS vaccine. The patient reported an intermittent fever of 101°F (38.3°C) but denied cough, chest pain, and dyspnea, and had otherwise normal vital signs. Serum lab test results were significant for elevated leukocytosis of 13.4 and CRP of 7.0, but were otherwise normal. The patient reported complete resolution of his symptoms after a 14-day follow-up via phone call.

CONCLUSIONS: Mpox is unfortunately spreading across the globe; therefore, many treatments and vaccines are being studied to address the outbreak. The latest generation of vaccines employ an attenuated vaccinia virus and are separated into replicating and non-replicating categories, and while generally safer than previous variola vaccines, they still are associated with rare complications and adverse effects. Generally, vaccinia symptoms are mild and self-resolving. Treatment is largely supportive and most patients can be discharged following general serum lab work-up and cardiopulmonary assessment.

Keywords: DNA Polymerase, Vaccinia virus, MVA Pfs25-IMX313 Malaria Vaccine, Smallpox Vaccine, Vaccinia virus, Humans, Male, Middle Aged, Vaccinia, Monkeypox, HIV Infections

Background

While smallpox has essentially been eradicated thanks to vaccinia-based vaccines, the emergence of the monkeypox virus (mpox) is requiring a large-scale re-administration. Many physicians have not been exposed to the rare, but implicit, complications, revealing a glaring need for updated evidence and re-examination. We present a case of a Human Immunodeficiency Virus (HIV)-positive male patient who presented to the Emergency Department (ED) with several days of vaccinia symptoms that began shortly after receiving the vaccine. These symptoms, along with management, prognosis, and prevention will be examined. In addition, the paper will briefly assess and review various vaccinia vaccines and the mpox disease.

Case Report

A 45-year-old man with a past medical history of well-controlled HIV presented to the ED for 5 days of nocturnal diaphoresis, chills, intermittent arthralgia, and myalgia. The patient reported an intermittent fever of 101°F (38.3°C) but denied cough, chest pain, and dyspnea. Upon arrival to the ED, the patient was afebrile with normal vital signs. Mild tenderness was elicited at the injection site, but no erythema or swelling was appreciated. Additionally, the patient did not have signs of lymphadenopathy. He was a well-appearing male in no acute distress, with all systems, including ENT, dermatologic, lymphatic, and cardiopulmonary evaluation, being grossly benign. Given the patient’s HIV status, prophylactic administration of the Modified Vaccinia Ankara (MVA) vaccine, JYNNEOS, was administered by his primary care physician 5 days prior to his ED visit. His symptoms began several hours after the injection.

Serum laboratory evaluation revealed a leukocytosis of 13.4 (×103/u) and elevated inflammatory markers with a C-reactive protein (CRP) of 7.0 mg/dL and an erythrocyte sedimentation rate (ESR) of 11 mm/h. Complete metabolic panel, troponin, and urinalysis were within normal limits, and the initial viral studies, corona virus disease 2019 (COVID-19) and influenza A/B antigens were negative as well. Chest X-ray did not demonstrate an acute cardiopulmonary process, and the electrocardiogram showed sinus rhythm with normal rate, interval, and axis. Given that there were no other sources of infection discovered, in conjunction with the symptoms beginning so soon after administration, the patient was likely to have been suffering from vaccinia secondary to the JYNNEOS vaccine.

The patient was closely monitored while in the ED, and remained stable throughout his stay, endorsing a symptomatic improvement with intravenous (IV) ketorolac 30 mg and 1 liter of normal saline fluid bolus. After ensuring the patient had close and proper follow-up, he was provided strict return precautions and was discharged. The patient reported complete resolution of his symptoms at 14-day follow-up via phone call.

Discussion

The orthopoxvirus family are large, double-stranded DNA viruses. The 2 noteworthy human-specific viruses are variola, the causative agent of smallpox, and the lesser-known vaccinia virus [1]. Vaccinia’s similar molecular makeup to variola, coupled with significantly less virulence, makes it an ideal instrument in creating smallpox vaccines [1]. Currently, only select groups continue to be vaccinated against variola: laboratory researchers that work with the virus, select healthcare workers, and the United States military [2]. Regarding mpox, the Centers for Disease Control (CDC) recommends vaccination for high-risk populations; chiefly those with multiple sexual partners, history of sexually transmitted infections (STIs), who engage in risky sexual behaviors, and immunocompromised [2]. As was seen with our patient, immunocompromised patients are preferentially given the highly-attenuated vaccinia-based JYNNEOS vaccine [3].

Various novel generations and preparation of the vaccinia virus vaccine have been created, with JYNNEOS being the latest third-generation version [4]. These latest-generation vaccines employ an attenuated vaccinia virus and are separated into replicating and non-replicating categories. JYNNEOS is one of several modified vaccinia virus Ankara (MVA) vaccines, using the Ankara strain of vaccinia [5]. The Ankara strain of vaccinia has been formulated in such a way to eliminate its replication abilities, distinctly separating it from other vaccines, subsequently making it ideal for immunocompromised patients [5]. It innately elicits a significantly decreased antibody response, further making it ideal for immunocompromised individuals [5]. Adverse effects are relatively rare and varied, and usually include a combination of polyarthralgia and fever, as was seen in our patient [4,5]. Other adverse effects include pain and swelling at the injection site, myalgia, weakness, fatigue, and lymphadenopathy [4,5]. The JYNNEOS vaccine was approved in 2019 for the prevention of both smallpox and mpox, specifically for immunocompromised patients [4,6–8]. These safety features come at a cost, however. By making the vaccine slightly less immunogenic, it could be considered to slightly less effective than its attenuated replicating counterparts, namely the LC16m8 (Lister clone 16, medium pocks, clone 8) made in Japan [9]. LC16m8 utilizes a truncated version of vaccinia which allows it to replicate and produce a sufficient immunogenic response, with an adverse effect profile similar to that of MVA vaccines [9]. All vaccinia-based vaccines, whether replicating or non-replicating, are contraindicated in pregnancy, as are most other attenuated vaccines [10].

Mpox is largely endemic to central and western regions of Africa, with outbreaks outside these regions being linked to international travel and animal importation [11]. Animal-to-human transmission is mainly through penetrating the skin, such as bites or scratches, while transmission between humans is largely through direct and prolonged skin-to-skin contact with the lesions, typically during sexual intercourse, or by contaminated fomites [12]. Respiratory and droplet modes of transmission have been reported, but these are extremely rare and only occur with prolonged exposure in an enclosed space [12]. There is no evidence of sexual transmission through seminal or vaginal fluids [11]. As to why mpox has spread to the Western world, current theories relating to waning smallpox immunity, COVID-19 prevention measures, and resumption of international travel and larger gatherings, seem to be the most widely accepted [11].

Mpox symptoms usually begin as a viral prodrome, fevers and chills being the most common features, followed by lymphadenopathy, lethargy, and headaches [13]. The disease then progresses to the characteristic rash, most commonly beginning in the anogenital region, then spreading to the axilla, extremities, and face [13]. The rash typically appears as a macule and quickly progresses to papules, extremely tender vesicles, and eventually crusted lesions [13]. Optimal diagnosis is based on polymerase chain reaction (PCR) from skin samples of unroofed lesions. The majority of cases are self-limited but some patients require hospital admission for disseminated disease and pain control [11]. The vesicles can be painfully debilitating depending on their extent and distribution. There are rarely reported complications of myocarditis or epiglottitis, but most self-resolve [11]. Mpox disproportionally affects men who have sex with men, particularly during prolonged sexual contact, but can occur in any population [11].

Regarding mpox treatment, most cases are self-limited and managed by supportive care [13]. If antiviral interventions are indicated, there are 3 main agents: tecovirimat, brincidofovir, and cidofovir [13]. Of note, none of the treatments have undergone randomized controlled trials (RCTs) in the treatment for mpox [13]. There are trials currently underway to explore use of the vaccines in a post-exposure prophylaxis setting [8].

Conclusions

Mpox is unfortunately spreading across the globe and as such, many treatments and vaccines are being studied to address the outbreak. The latest-generation vaccines employ an attenuated vaccinia virus and are separated into replicating and non-replicating categories. While generally safer than previous variola vaccines, they still are associated with rare complications and adverse effects. Generally, vaccinia symptoms are mild and self-resolving, as was the case with our patient. Treatment is largely supportive and most patients can be discharged following general serum lab work-up and cardiopulmonary assessment.

References:

1.. Moss B, Poxvirus DNA replication: Cold Spring Harb Perspect Biol, 2013; 5(9); a010199

2.. , JYNNEOS vaccine. Updated December 22, 2022. Accessed December 23, 2022. https://www.cdc.gov/poxvirus/monkeypox/interim-considerations/jynneos-vaccine.html#interim

3.. Williams PN, Titanji B, Gandhi MM, The curbsiders internal medicine podcast. #359 Monkeypox with Dr. Titanji. October 10, 2022. Accessed November 13, 2022. https://thecurbsiders.com/episode-list

4.. Kennedy JS, Greenberg RN, IMVAMUNE: Modified vaccinia Ankara strain as an attenuated smallpox vaccine.: Expert Rev Vaccines, 2009; 8(1); 13-24

5.. Volz A, Sutter G: Adv Virus Res, 2017; 97; 187-243

6.. Greenberg RN, Hay CM, Stapleton JT, A randomized, double-blind, placebo-controlled phase II trial investigating the safety and immunogenicity of modified vaccinia Ankara Smallpox vaccine (MVA-BN®) in 56–80-year-old subjects: PLoS One, 2016; 11; e0157335

7.. Greenberg RN, Overton ET, Haas DW, Safety, immunogenicity, and surrogate markers of clinical efficacy for modified vaccinia Ankara as a smallpox vaccine in HIV-infected subjects: J Infect Dis, 2013; 207; 749

8.. Morgan CN, Whitehill F, Doty JB, Environmental persistence of monkeypox virus on surfaces in household of person with travel-associated infection, Dallas, Texas, USA, 2021: Emerg Infect Dis, 2022; 28(10); 1982-89

9.. Kenner J, Cameron F, Empig C, LC16m8: An attenuated smallpox vaccine: Vaccine, 2006; 24(47–48); 7009-22

10.. Rotz LD, Dotson DA, Damon IK, Vaccinia (smallpox) vaccine: Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2001: MMWR Recomm Rep, 2001; 50(RR-10); 1 -CE7

11.. Thornhill JP, Barkati S, Walmsley S, Monkeypox virus infection in humans across 16 countries – April–June 2022: N Engl J Med, 2022; 387(8); 679-91

12.. Vaughan A, Aarons E, Astbury J, Human-to-human transmission of Monkeypox virus, United Kingdom, October 2018: Emerg Infect Dis, 2020; 26(4); 782-85

13.. Titanji BK, Tegomoh B, Nematollahi S, Monkeypox: A contemporary re -view for healthcare professionals: Open Forum Infect Dis, 2022; 9(7); ofac310

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American Journal of Case Reports eISSN: 1941-5923
American Journal of Case Reports eISSN: 1941-5923