Monkeypox is Spreading Fast but It Can Be Prevented

by Margaret Moore, Doctor of Pharmacy Candidate and Kayla R. Stover, PharmD, BCIDP, BCPS

The U.S. officially declared monkeypox a national health emergency on August 5, 2022. The CDC reports 11,177 cases (as of August 12, 2022), with hotspots in California, New York, Florida, and Illinois.¹ Although this virus can affect anyone, the majority of infected individuals in the U.S. are men who have sex with men.

Monkeypox is caused by a zoonotic virus that belongs to the Orthopoxvirus genus.² The first human case of monkeypox was reported in 1970.³ Because the monkeypox virus is in the same genus as the variola virus (which causes smallpox), it is believed that individuals who received the smallpox vaccine have some cross-immunity to the monkeypox virus.² Studies show that 90% of volunteers who received the smallpox vaccination (before 1970, when widespread vaccination was discontinued) still have humoral or cellular immunity against vaccinia, the virus used in the smallpox vaccine.⁴ Contrary to the name, the true origin of monkeypox is unknown.³  Rodents and other small mammals, not monkeys, have been implicated as possible sources.⁵

The clinical presentation of monkeypox resembles that of smallpox, but the symptoms are typically milder. Monkeypox is spread primarily by skin-to-skin contact with a rash, scab, or fluids of an infected individual. Other modes of transmission include maternal-fetal placental transmission, through respiratory secretions, scratches/bites from infected animals, and touching objects/surfaces that have been used by someone with monkeypox.¹ Monkeypox remains contagious from the onset of symptoms until the rash is fully healed, which is typically 2-4 weeks.³

Signs and Symptoms

Within one to two weeks of infection, patients may experience nonspecific flu-like symptoms, such as fever, enlarged lymph nodes, general malaise, and muscle pains. The skin rash/lesions associated with monkeypox usually develop within one to three days after the onset of fever.⁶ The rash is most commonly found on the face, extremities, and mucous membranes, and it can be very painful. The lesions evolve through four sequential stages, starting with macules (lesions with a flat base) to papules (slightly raised and firm) to vesicles (filled with clear fluid), and finally, pustules (filled with yellowish fluid).⁶ The lesions then scab over and regenerate new skin.  Only after the lesions are fully healed is an individual considered non-contagious.

Although monkeypox tends to follow a milder course than smallpox infections, some patients experience complications, including corneal infection with permanent scarring, cellulitis, sepsis, and encephalitis.²

Prevention and Protection

To help prevent the spread of monkeypox, patients and healthcare workers should avoid skin-to-skin contact with people who have a rash or lesions. Avoid touching objects that a person with monkeypox has used, such as eating utensils, bedding, towels, and clothing. Proper hand hygiene should always be practiced.

There are currently two vaccines to prevent monkeypox: JYNNEOS and ACAM2000.⁶ JYNNEOS is an FDA-approved vaccine for monkeypox; ACAM2000 is approved for smallpox but is allowed for use in monkeypox under an expanded-access IND protocol. A study from Africa found that the smallpox vaccine is at least 85% effective in preventing monkeypox.⁵ The CDC recommends that a person who is exposed to monkeypox receive either vaccine within four days to prevent disease onset.⁶ While receiving the vaccine 4-14 days after exposure will not prevent the disease; it may reduce symptoms. Given the declaration of a national health emergency, both vaccines are free of charge through the Strategic National Stockpile (SNS) to any eligible patient. The current eligibility criteria for the vaccines are:⁷

• Persons who have been in close contact with someone infected with monkeypox
• Persons who have had multiple sex partners in the last two weeks within an area with a high number of confirmed cases of monkeypox
• Men who have sex with men and their sexual partners

Vaccinations to Prevent Monkeypox

	JYNNEOS	ACAM2000
Mechanism of Action	Contains live Vaccinia virus that does NOT replicate efficiently in human cells	Contains live Vaccinia virus that replicates
Series	2 doses, 28 days apart	1 dose
Dosage	0.5 mL	0.0025 mL
Time to Maximal Immunity	14 days after the second dose	4 weeks
Adverse Reactions	Injection site reactions (swelling, pain, and redness) Fatigue, headache, and muscle pain	Injection site reactions (redness, swelling, and pain) Fever, rash, lymph node swelling Myocarditis and/or pericarditis
Use Caution	Patients with a prior allergic reaction to the vaccine.  Patients under the age of 18  If a patient develops monkeypox symptoms after their first dose, it is not recommended to receive the second dose (unless immunocompromised)	Patients with a prior allergic to the vaccine Patients with the following conditions: *Congenital or acquired immune deficiency disorders *Eczema or other exfoliative skin conditions *Pregnancy *Eye disease treated with topical steroids
Contraindications		Persons with severe immune deficiency

Treatment

Currently, there are no FDA-approved treatments for monkeypox, but treatments that have been used for smallpox have been evaluated.⁸ Current medications being investigated include cidofovir, brincidofovir, vaccinia immune globulin (VIG), and tecovirimat, with tecovirimat being the forerunner. Cidofovir and brincidofovir are antivirals approved for the treatment of cytomegalovirus and smallpox, respectively.  Both are associated with serious renal toxicity, thereby limiting their use.^11-12 Although VIG is not approved for the treatment of monkeypox, it is FDA approved for the treatment of complications from vaccinia vaccination — specifically, eczema vaccinatum and certain skin infections. Tecovirimat is an antiviral approved for the treatment of smallpox.  Recent studies have shown it to be effective in the treatment of monkeypox in animal studies.⁸ Tecovirimat is currently available to the public for free through an expanded-access protocol from the CDC.  The CDC recommends the use of tecovirimat in the following patients:¹⁰

• Those with severe disease (conditions requiring hospitalization)
• Lesions in any areas that constitute a special hazard (eyes, mouths, genitals, or anus)
• Those who are at risk for severe disease
  • Immunocompromised patients (HIV, cancer, transplant)
  • Pediatric patients, especially patients younger than 8 years old
  • Pregnant or breastfeeding women
  • History of atopic dermatitis or other exfoliative skin conditions (eczema, impetigo, herpes)
  • People with one or more complications (bacterial skin infection, gastroenteritis, bronchopneumonia)

Tecovirimat is available as a 200 mg capsule or an IV injection. Under the CDC’s expanded access IND protocol, tecovirimat can be used for primary treatment of monkeypox as well as post-exposure prophylaxis.¹³ The most common side effects of the oral formulation are headache, nausea, and abdominal pain, while the IV formulation can cause infusion site pain, swelling, and erythema. Tecovirimat has been found to have significant interactions with repaglinide (hypoglycemia) and midazolam (which reduces the effectiveness of midazolam).

Tecovirimat: Dosing Information

Route of Administration	Dosage based on patient weight	Treatment duration	Renal impairment	Hepatic impairment
Oral	40-120 kg: 600 mg PO q12 hr >120kg: 600 mg PO q8 hr	14 days, but maybe longer or shorter depending on disease progression Not to exceed 90 days	No dose adjustment required	No dose adjustment required
IV	35-120 kg: 200 mg IV q12 hr >120 kg: 300 mg IV q12 hr	Switch to capsules as soon as oral treatment can be tolerated to complete the treatment course	CrCl > 30 mL/min: no dosage adjustment CrCl <30 mL/min: contraindicated	No dose adjustment required

References