CryptoPolyTech Press Pass Coverage of Monkeypox Treatment and Prevention: Stopping the Latest Outbreak

What is Monkeypox Virus?

The discovery of monkeypox virus (MPV) dates back to 1958 when a group of monkeys used for research purposes were infected in Denmark.¹ Despite these cases and the name of the virus, the original source of the disease remains unknown. Similar to smallpox, MPV belongs to the variola virus family.²

The first human case of MPV was reported in 1970 in Central Africa. Prior to the current 2022 outbreak, cases were primarily identified and reported in the Central and Western regions of Africa.¹

As of September 2022, there more than 22,000 reported cases in the United States alone and more than 59,000 cases globally.³ States with the most reported cases include California, Florida, Georgia, Illinois, New York, and Texas. Currently, data suggest that men who have sex with men (MSM) make up the majority of cases in the outbreak.

Signs and Symptoms

The primary sign of MPV infection is rash near the genitals, anus, lower extremities, chest, face, or mouth.^2,4 Typically, the rash presents as painful and/or itching blisters or pimples and progresses through several different stages, including scabbing, prior to healing.

Other common signs and symptoms that typically occur as a febrile prodrome include swollen lymph nodes, fatigue, and flu-like symptoms (e.g., muscle aches, nasal congestion, cough, sore throat, chills, and headache). Symptom onset takes place within 3 weeks following exposure and can last 2 to 4 weeks.

The virus is typically spread through direct skin-to-skin contact with an infected lesion, bodily fluids, and/or respiratory secretions. This contact can occur during intimate contact, face-to-face contact, and touching fabrics or objects that have been contaminated by an infected person’s bodily fluids. Currently, diagnostic testing is only recommended for individuals with active visible rash.

Treatment

There are currently no treatments approved specifically for MPV.⁵ Medications currently used for the treatment of MPV have not been studied for efficacy in humans but have shown benefit in animal studies.

Tecovirimat (TPOXX), an antiviral medication used to treat smallpox, is now being used for the treatment of MPV as primary or empiric treatment in adults and children of all ages under the FDA Expanded Access Investigational New Drug (EA-IND) program.^5,6

Tecovirimat may be considered for treatment of MPV in those who present with more severe cases or for those who are immunocompromised due to other comorbid conditions, such as HIV/AIDS, autoimmune diseases, malignancies, solid organ transplant and hemopoietic stem cell transplants, among others.

Furthermore, treatment with tecovirimat is recommended for those who are pregnant or breastfeeding, patients with skin conditions, and pediatric populations, specifically, those under the age of 8. Dosing for tecovirimat is weight-based and can be administered intravenously (IV) or orally.

Oral treatment is preferred for all patients who are eligible for treatment, and it is recommended the patient be converted from IV to oral as soon as they can tolerate it. The oral formulation is available as a 200 mg capsule that requires a full meal with fats for adequate absorption.

Common adverse effects (AEs) of the oral formulation include headache, nausea, vomiting, and abdominal pain, whereas AEs for the IV formulation include infusion site pain, swelling, erythema, and extravasation. The treatment duration for all patients, regardless of age, is 14 days.

Research examining use beyond 14 days is limited. Special circumstances may require longer treatment depending on the progression of disease or the clinical presentation of the patient, but overall duration of treatment should not exceed 90 days.

Alternative medications to tecovirimat that have been considered for the treatment of MPV include intravenous Vaccinia immune globulin (VIGIV), cidofovir, and brincidofovir.⁵ VIGIV is currently approved to treat complications of smallpoxvaccination but is available through an expanded access protocol for the treatment of other orthopox viruses.⁷

Because the efficacy of VIGIV is unknown, it is recommended that it only be considered in severe cases or for prophylactic use in patients with severe T-cell immunodeficiency in which vaccination with Jynneos or ACAM2000 would be contraindicated.⁵ Cidofovir has been shown to be effective against orthopox viruses in vitro and against vaccinia virus in mice.

Cidofovir is only available in an IV formulation and has been associated with serious renal toxicity.⁸ It is not known whether cidofovir is effective for the treatment of MPV.

Finally, brincidofovir has shown promise in reducing mortality from MPV in animal studies when given shortly after exposure.⁹ It is available as an oral medication and does not carry the same risk of renal toxicity as cidofovir; however, brincidofovir is not yet available under an Expanded Access Investigational New Drug Application (EA-IND) for MPV.⁵

Prevention

Two vaccines are currently being used for MPV prevention: Jynneos and ACAM2000. Preventative vaccination is given both as pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP).¹⁰

PrEP is only recommended for those at high risk, such as laboratorians directly handling specimens and MSM. This is not because it is a sexually transmitted infection, but merely the network that has been most affected by the current MPV outbreak.

PEP is recommended for those with known exposure to MPV within the preceding 4 days. If either of the available vaccines is given between 4 and 14 days post-exposure, it may not prevent illness, but may help reduce the severity of symptoms.

Jynneos is the primary vaccine used for prevention and was approved by the FDA for subcutaneous administration in those 18 years of age and older who are determined to be at high risk for smallpox or monkeypox infection.¹¹ Additionally, there is an FDA Emergency Use Authorization (EUA) in place for 0.1 mL intradermal administration in those 18 years of age and older and 0.5 mL subcutaneous administration in the pediatric population or patients with a history of keloid scarring.¹⁰

The vaccine, given by either route of administration, is to be given as two-dose series, 28 days apart. Current CDC guidance does not identify a minimum age for vaccination with Jynneos and offers alternative administration for those under the age of 12 months, subcutaneously in the anterolateral thigh. It is a live, non-replicating vaccine with common AEs including injection site reactions, pruritus, fatigue, loss of appetite, muscle pain, and headache.¹¹

ACAM2000 is the alternative vaccine licensed by the FDA for immunization against smallpox disease for people determined to be at high risk for smallpox infection.¹² It has been made available for the prevention of monkeypox infection under an EA-IND.¹⁰

It is given in a single dose through the percutaneous route using a multiple puncture technique to deliver 15 punctures.¹² The safety and efficacy of this vaccine has not been studied in patients under 16 years of age, and therefore is not approved for use by the FDA in these patients.

However, interim guidance from the CDC recommends using this vaccine for anyone over 1 year of age who is deemed to be high-risk for acquiring MPV.¹⁰ It is recommended that the vaccination site be evaluated within 8 days following administration.

A red, itchy sore, sometimes referred to as a “take” should be observed thus indicating a successful vaccination. This reaction can be seen as an umbilicated vesicle that eventually becomes pustular within 11 days of the receiving the vaccine.¹²

ACAM2000 is a live, replicating vaccine and has a similar AE profile to the Jynneos vaccine.

Conclusion

Currently, there is no FDA-approved treatment available for monkeypox, but existing antiviral agents have been found to be effective in vitro and in animal studies. Two existing smallpox vaccines, Jynneos and ACAM200, are currently being used for MPV infection prevention.

Overall, the current monkeypox outbreak continues to evolve with new evidence emerging almost daily.

References

1. Bunge EM, Hoet B, Chen L, et al. The changing epidemiology of human monkeypox-A potential threat? A systematic review. PLoS Negl Trop Dis. 2022;16(2):e0010141. Published 2022 Feb 11. doi:10.1371/journal.pntd.0010141
2. Centers for Disease Control and Prevention. About Monkeypox. Accessed August 30, 2022.
3. Centers for Disease Control and Prevention. 2022 Outbreak Cases and Data. Accessed August 30, 2022.
4. Minhaj FS, Ogale YP, Whitehill F, et al. Monkeypox Outbreak — Nine States, May 2022. MMWR Morb Mortal Wkly Rep. 2022;71(23):764-769. doi:10.15585/mmwr.mm7123e1
5. Centers for Disease Control and Prevention. Clinical Guidance. https://www.cdc.gov/poxvirus/monkeypox/clinicians/clinical-guidance.html. Accessed August 30, 2022.
6. Rizk JG, Lippi G, Henry BM, Forthal DN, Rizk Y. Prevention and Treatment of Monkeypox [published correction appears in Drugs. 2022 Aug 22;:]. Drugs. 2022;82(9):957-963.
7. CNJ-016 [package insert]. Winnipeg, Canada: Cangene Corporation; 2005.
8. De Clercq E. Cidofovir in the treatment of poxvirus infections. Antiviral Research. 2002;55(1):1-13. doi:10.1016/S0166-3542(02)00008-6
9. Hutson CL, Kondas AV, Mauldin MR, et al. Pharmacokinetics and Efficacy of a Potential Smallpox Therapeutic, Brincidofovir, in a Lethal Monkeypox Virus Animal Model. Schoggins J, ed. mSphere. 2021;6(1):e00927-20. doi:10.1128/mSphere.00927-20
10. Centers for Disease Control and Prevention. Interim Clinical Considerations for Use of JYNNEOS and ACAM2000 Vaccines during the 2022 U.S. Monkeypox Outbreak. Accessed August 30, 2022.
11. JYNNEOS [package insert]. Denmark: Bavarian Nordic A/S; 2019.
12. ACAM2000 [package insert]. Gaithersburg, MD: Emergent Product Development Gaithersburg Inc; 2007.

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