Monkeypox Update

Educational Objectives

The goal of this program is to improve outcomes in HIV patients with monkeypox (mpox) virus infection. After hearing and assimilating this program, the clinician will be better able to:

1. Differentiate symptoms of mpox virus infection from those of other skin conditions.
2. Evaluate the efficacy of mpox vaccination in HIV patients.
3. Recommend preventive measures for mpox virus infection.

Summary

Monkeypox (mpox) virus: part of the Orthopoxvirus genus that causes smallpox-like lesions; antibody surveys reveal that it is spread to humans via bites or scratches from squirrels or giant Gambian rats or exposure to the skin lesions of rodents; monkeys are not responsible for this infection; the West African strain has a mortality rate of ≤2%, whereas the Central African strain has a mortality rate of ≈10%; most deaths are in children <3 yr of age; Nigeria has had a significant surge in mpox since 2017; the current outbreak is probably an imported case from Nigeria; this variant causes less severe disease; spread — mostly through very close person-to-person contact via lesions on the skin, mouth, rectal, or penile region; seminal fluid from ejaculate is positive in 90% of cases and can remain positive ≤19 days after the first symptom manifests; also found in saliva and rectal sample in 90% of cases, even in the absence of any lesions; may also be transmitted via contaminated clothes or environmental surfaces and droplet secretions

Current mpox virus epidemic: first detected in the United Kingdom in a traveler from Nigeria; 98% of cases are reported in men, specifically men who have sex with men; the median age of patients is 35 yr; globally, the number of reported cases has declined by 25%; incubation period is an average of 7 days (6-10 days) but could be ≤20 days after exposure

Symptoms: initial symptoms in the African variant are fever, headache, muscle aches, and exhaustion; rash starts 3 days after the initial symptoms, starting initially on the face, then spreading to the body, hands, and feet; in the current outbreak, the lesion initiates at the penile region before spreading to other areas; the first lesions occur at site of virus inoculation; there may or may not be fever; lesions remain infectious until the scabs have fallen off and the underlying skin heals; illness lasts for 2 to 4 wk; in a study of 180 patients with mpox, 78% had anogenital region lesions, 25% had inflammation of the rectum or proctitis, 8% had penile edema, 43% had oral and perioral lesions, and 10% had tonsillitis; mpox causes localized enlargement of lymph nodes; stages include flat lesion, papule, vesicle, and pustules; pustule rupture leads to scab formation

Asymptomatic mpox: in a study by Ferré et al (2022), ≈7% of patients tested positive for mpox despite having no symptoms, however, 2 patients developed anal rash and pharyngitis; ≈5% of people can have no symptoms or lesions while having infectious virus

Mpox in HIV: ≈40% of mpox cases also have HIV; HIV status does not impact the time taken to develop symptoms; if the patient is on antiretroviral therapy (ART) and controlled, mpox is no different than being HIV-negative; in a recent study, more HIV-infected people were hospitalized (mainly because of secondary infection and pain) than non-HIV patients; more hospitalizations are reported in people with unsuppressed viral load; in Nigeria, since ART is not very common, cases of advanced HIV have been reported, 6% of whom died, and 4 of the 7 who died had HIV; patients with high viral load had long illness, larger lesions, and more secondary infections

Diagnosis: samples taken from pustules or swabs (taken from the base of the lesion) are tested using polymerase chain reaction

Measures in suspected cases: patients should visit the local health department in their city of residence, preferably via appointment, as they can perform tests, provide results, and have options for treatment; 40% of patients with mpox have had a sexually transmitted infection (STI) within the previous year; check for Chlamydia gonorrhea and syphilis

Mpox treatment: tecovirimat (TEC; eg, TPOXX) — approved for smallpox; inhibits VP37 (protein) and prevents the release of virions; presumed to have good efficacy, as all pox viruses have VP37; oral dose is 200 mg twice daily for 14 days; also available in intravenous formulation; should be taken within 30 min of a high-fat meal to ensure absorption; patients may also open the capsule and dissolve contents in milk or soft food

Treatment criteria: severely ill patients require hospitalization; patients with ocular, oral, or genital involvement require treatment, as strictures in the penis and rectal lesions may develop; other criteria include immunocompromise, age <8 yr, pregnancy and breastfeeding; patients with skin lesions (eg, atopic dermatitis, eczema, psoriasis) may have broader-spread mpox lesions; well-controlled HIV is not an indication to treat but could be considered in cases of cluster of differentiation 4 (CD4) cell count <200 cells/mm³, persistent viremia, or diagnosis with HIV within the last 6 mo; TEC reduces the level of rilpivirine (RPV); patients on combination cabotegravir (CAB) plus RPV (Cabenuva) require 25 mg of RPV once daily during and for 2 wk after completion of TEC therapy; do not start CAB-RPV until 2 wk after discontinuation of TEC therapy

Efficacy of treatment: no information on efficacy is available; the National Institutes of Health (NIH) initiated a multicenter trial across the United States to determine the efficacy of TEC and development of resistance; single mutation, as is the case with HIV, may lead to total resistance

Prevention: the smallpox and mpox vaccine (eg, JYNNEOS [live, nonreplicating vaccine]) is available; researchers have weakened and mutated the virus to prevent replication; approved for smallpox and mpox; it is a subcutaneous (SQ) 2-dose series administered 20 days apart; each dose is 0.5 mL; Frey et al (2015) saw similar immune response with full SQ dose vs 20% of the intradermal (ID) dose; ID administration may cause redness and skin-thickening (not recommended in people with a history of developing keloids); African American individuals have a 20-fold higher risk of developing keloids with ID route compared with White individuals; vaccination within 2 to 3 days of exposure completely protects from clinical disease; vaccination within 7 days of exposure prevents disease in ≈90% of patients; vaccination can be considered ≤2 wk after exposure; the vaccine is shown to provide similar protection in persons with well-controlled HIV vs uninfected persons

Indicators: include being in close contact with those infected with mpox or having sexual intercourse with a patient infected with the mpox virus or engaging in group sex; there is an ethnic disparity among those receiving the vaccine; Centers for Disease Control and Prevention developed the Monkeypox Vaccine Equity Pilot Program under which 5000 to 10,000 doses are delivered to gay events (eg, Oakland Pride) to ensure greater coverage

Efficacy of mpox vaccine: study of vaccine antibody response — showed relatively low levels of protective antibodies, which were also not protective enough to neutralize the virus; there were low antibody levels at 4 and 8 wk, and the second dose resulted in detectable antibodies; although it may not provide complete protection from infection, the vaccine may alter the severity of infection

Preventive measures: avoid activities that increase risk for mpox exposure until ≥2 wk after second dose; limit number of sex partners; avoid spaces where anonymous sex occurs, eg, backrooms, saunas, sex clubs, public sex parties; discuss with partners whether they might have any symptoms of mpox; condoms may provide limited protection as skin lesions could be anywhere on the body; avoid touching rashes or scabs of other people and do not share eating utensils and other personal items; wash hands with soap and water and use an alcohol-based sanitizer; wear a mask in case of prolonged face-to-face contact; avoid kissing; consider masturbation at a distance or virtual sex with no physical contact; 50% of mpox cases result from one-time sex; person and their partner should avoid having sex of any kind if there are rashes or lesions on the body and should contact health care providers; at the clinic, the sample should be frozen or refrigerated until pickup; abstinence is recommended for 8 wk after first symptom of mpox

Readings

Ferré VM, Bachelard A, Zaidi M, et al. 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. Ann Intern Med. 2022;175(10):1491-1492. doi:10.7326/M22-2183; Fischer F, Mehrl A, Kandulski M, et al. Monkeypox in a patient with controlled HIV infection initially presenting with fever, painful pharyngitis, and tonsillitis. Medicina(Kaunas). 2022;58(10):1409. Published 2022 Oct 7. doi:10.3390/medicina58101409; Frey SE, Wald A, Edupuganti S, et al. Comparison of lyophilized versus liquid modified vaccinia Ankara (MVA) formulations and subcutaneous versus intradermal routes of administration in healthy vaccinia-naïve subjects. Vaccine. 2015;33(39):5225-5234. doi:10.1016/j.vaccine.2015.06.075; Hoffmann C, Jessen H, Wyen C, et al. Clinical characteristics of monkeypox virus infections among men with and without HIV: A large outbreak cohort in Germany. HIV Med. 2022; 1- 9. doi:10.1111/hiv.13378; Rao AK, Petersen BW, Whitehill F, et al. Use of JYNNEOS (Smallpox and Monkeypox Vaccine, Live, Nonreplicating) for preexposure vaccination of persons at risk for occupational exposure to orthopoxviruses: Recommendations of the Advisory Committee on Immunization Practices - United States, 2022 [published correction appears in MMWR Morb Mortal Wkly Rep. 2022 Jul 08;71(27):886]. MMWR Morb Mortal Wkly Rep. 2022;71(22):734-742. Published 2022 Jun 3. doi:10.15585/mmwr.mm7122e1; Tarín-Vicente EJ, Alemany A, Agud-Dios M, et al. Clinical presentation and virological assessment of confirmed human monkeypox virus cases in Spain: a prospective observational cohort study. Lancet. 2022;400(10353):661-669. doi:10.1016/S0140-6736(22)01436-2; Zaeck LM, Lamers MM, Verstrepen BE, et al. Low levels of monkeypox virus neutralizing antibodies after MVA-BN vaccination in healthy individuals [published online ahead of print, 2022 Oct 18]. Nat Med. 2022;10.1038/s41591-022-02090-w. doi:10.1038/s41591-022-02090-w.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Oldfield was recorded at the 2022 Eastern Region HIV/AIDS Fall Summit, held September 21, 2022, in Chesapeake, VA, and presented by Eastern Virginia Medical School. For information on future CME activities from this presenter, please visit https://www.evms.edu/education/cme/. Audio Digest thanks the speakers and Eastern Virginia Medical School for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 1.00 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 1.00 CE contact hours.

Lecture ID:

IM694701

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.