Mpox: Updates in Evaluation and Management

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The shifting sands of the 2022 mpox outbreak have left many health care professionals scrambling to keep up with the latest information and recommendations on how to care for patients infected or suspected to be infected with mpox. On the recent webinar “Mpox: Updates in Evaluation and Management,” three experts in clinical care for patients with infectious diseases share up-to-date research and practices for managing mpox. Here are the key takeaways from the presentation.

Epidemiology and Infection Prevention and Control

Current State of the Mpox Outbreak

As of September 26, 2022, the CDC had reported 65,993 cases globally in 106 countries, and 26 deaths (CDC, https://www.cdc.gov/poxvirus/monkeypox/response/2022/world-map.html, Accessed 9/30/2022). In the U.S., cases have reached 25,162 (CDC, https://www.cdc.gov/poxvirus/monkeypox/response/2022/us-map.html, Accessed 9/30/2022), accounting for 38 percent of the total cases and community transmission is now occurring in all 50 states. The WHO reported a 22% decrease in the number of reported cases the week of September 12, 2022, over the previous week.

How Mpox Spreads

While scientists are still researching several potential methods of transmission (CDC, https://www.cdc.gov/mpox/causes/, Accessed 2025), mpox is known to spread through:

• Close, personal, skin-to-skin contact​ with the rash, scabs, or body fluids from a person with mpox​;
• Contact with objects, fabrics (clothing, bedding, towels), and surfaces that have been contaminated with fluid from lesions, scabs, body fluids from a person with mpox​;
• Contact with respiratory secretions during prolonged face-to-face encounters​;
• During pregnancy, via placenta to fetus​; or
• From infected animals via scratch or bite, or by preparing or eating meat or using products from an infected animal​.

A person is infectious from the onset of symptoms until the rash has fully healed and a fresh layer of skin has formed, which can take 2-4 weeks​.

Infection Prevention and Control in Health Care Settings

Infection prevention and control approaches are aimed at breaking the chain of infection. Health care workers can break the chain or minimize the spread of infection by following the identify, isolate, and inform strategy; consistently adhering to standard and transmission-based precautions; and properly managing waste.

Identify, Isolate, and Inform

• Identify the potential for infection when evaluating a patient by taking a through travel history and reviewing symptoms and other relevant epidemiological factors. See the CDC case definition for mpox. While identification may be based on the CDC’s official definition of a person under investigation, health care providers should maintain clinical suspicion even if the epidemiology doesn’t fit. Patients with mpox can present a range of signs and symptoms.
• Isolate the patient immediately in a private standard patient room, or an airborne infection isolation room if aerosol generating procedures are anticipated, and don personal protective equipment. (See standard and transmission-based precautions below)
• Inform relevant personnel in your health care facility, including the infection control department and possibly public health personnel.

Watch NETEC’s webinar The I’s Have It: Identify, Isolate, and Inform to learn more.

Standard and Transmission-Based Precautions

Health care personnel should strictly adhere to standard and transmission-based precautions when managing patients infected or suspected to be infected with mpox. See the CDC’s guide for Standard Precautions for All Patient Care (CDC, https://www.cdc.gov/infectioncontrol/basics/standard-precautions.html, Accessed 9/30/2022) and Transmission-Based Precautions (CDC, https://www.cdc.gov/infectioncontrol/basics/transmission-based-precautions.html, Accessed 9/30/2022).

• Personal protective equipment (PPE): PPE should include a NIOSH-approved, fit-tested N-95 respirator, gown, gloves, and eye protection with face shield or goggles (CDC, https://www.cdc.gov/poxvirus/monkeypox/clinicians/infection-control-healthcare.html, Accessed 9/30/2022). Some jurisdictions recommend an N95 respirator only in settings where aerosol-generating procedures ​are performed.
• Patient placement: A patient suspected of or confirmed to have mpox should be placed in a private room; utilize an airborne infection isolation room if aerosol generating procedures are anticipated. Keep the patient room door closed and restrict access to the room to designated personnel. The patient should wear a surgical/medical mask when outside the room and when inside the room and interacting with health care personnel or permitted visitors. If transported outside of their room, any exposed lesions should be covered with a sheet or gown.

Managing Waste

During the current global outbreak, all cases are expected to be Clade II (previously named the West African Clade) and waste can be managed as Regulated Medical Waste (RMW). See the Department of Transportation website for more information (page 94). Facilities should also comply with state and local regulations (HER Center, Accessed 2025, https://www.hercenter.org/rmw/rmwlocator.php) for handling, storage, treatment, and disposal of waste.

• Soiled laundry, including protective clothing, bed linens, curtains, etc., should never be shaken or handled in a manner that may disperse infectious materials.
• All portable medical equipment and surfaces in the patient room should be cleaned and disinfected according to standard regulations using hospital-approved disinfectants and following directions for concentration, contact time, care, and handling.

For more information about infection prevention and control for mpox, visit the CDC webpage on Infection Prevention and Control of Mpox in Healthcare Settings (CDC, https://www.cdc.gov/poxvirus/monkeypox/clinicians/infection-control-healthcare.html, Accessed 9/30/2022).

Clinical Presentation, Patient Management, and Treatment

Key Characteristics of Mpox

The current outbreak is characterized by increased incidence of person-to-person spread through sexual contact, especially in gay, bisexual, and other men who have sex with men; frequent absence of prodrome​; and variability in rash presentation, with predominance in anogenital locations, often with concurrent STI​. Learn more about clinical characteristics (CDC, https://www.cdc.gov/poxvirus/monkeypox/clinicians/clinical-recognition.html, Accessed 9/30/2022).

Mpox: Then Vs. Now

Characteristic	Classic (Textbook) Description​	2022 Outbreak​
“Typical” Exposure​	Exposure to animals in West/Central Africa; person-to-person less common​	Person-to-person transmission through intimate or sexual contact, especially in MSM​
Incubation Period​	1-2 weeks	Median 7 days, range 5-21 ​(some reports of <5 days)​
Prodrome Symptoms​	Fever, malaise, lymphadenopathy for 1-5 days​	Not always present​
Lesion Description​	Firm, well-circumscribed, deep-seated, and often umbilicated. ​All in same stage	Atypical appearances described; may mimic other diseases (i.e., syphilis, HSV). ​May not be in the same stage​
Lesion Distribution​	Predominantly disseminated involving face, trunk, palms/soles​	Predominantly genitals, anorectal, oral. ​May be localized.
Lesion Number​	Variable	Variable; often <20 lesions​
Mortality	1-10%	Rare

Patient Demographic Characteristics in 2022

• Majority of cases managed in outpatient settings​
• Predominantly middle-aged males who report sexual or intimate contact with other men​
• Often report multiple recent sexual partners (73% with ≥2 partners within preceding 3 weeks, Philpott et al, MMWR Morb Mortal Wkly Rep. 2022 Aug 12)​
• High proportion of concurrent HIV or other sexually transmitted infections​

Clinical Presentation​

• Symptoms commonly include fever, lymphadenopathy, myalgias, headache​
• Prodrome symptoms often absent prior to rash onset​
• Rash distribution frequently involves anogenital region; rectal pain and bleeding are often reported​
• Number of lesions typically <20​

Lesion Characteristics

• Lesions are typically painful, may be pruritic​
• Lesions can be either disseminated or localized​
• Systemic symptoms may not always be present​
• Lesions are generally, but not always, present in the same stage​
• Pitted scars and/or areas of lighter or darker skin may remain after scabs have fallen off
• Considered infectious until all scabs have fallen off and a fresh layer of skin has formed​

Complications and Atypical Presentations

More Common Complications include:

• Painful rash​
• Proctitis / tenesmus ​
• Secondary skin infections​
• Pharyngitis​

Less common complications include:

• Encephalitis​
• Pneumonitis​
• Keratitis​
• Myocarditis​
• Abscess

Reasons for hospitalization:

• Pain management (especially for genitorectal pain)​
• Secondary bacterial infections​
• Limited PO intake (pharyngitis)​
• Ocular lesions​
• Acute renal insufficiency​
• Myocarditis​

Presentations associated with delayed recognition (anecdotal):

• Cellulitis (single lesion)​
• Pharyngitis prior to rash onset​
• “Incidental” rash​

Differential diagnosis may include syphilis; enteroviral infection (hand, foot, and mouth disease); herpes simplex virus, varicella zoster virus, and molluscum contagiosum. Co-infections do occur.

Diagnosing Mpox

Diagnostic testing for mpox virus is performed using a polymerase chain reaction (PCR) test of a specimen collected via a swab of lesions or lesion material. See NETEC’s learning module on how to collect a mpox specimen for diagnostic testing.

Ensure the lab is notified of any specimen from a mpox patient, as they may need to observe enhanced safety measures. Avoid transport practices that may lead to accidental exposure. Listen to the episode of Transmission Interrupted for a health care professional’s guide to mpox testing, laboratory procedures, and biosafety.​

Treatments for Mpox

Treatment of mpox is primarily supportive: ensuring adequate hydration and restoring fluid losses, treatment of complications, and pain control. However antiviral treatment should be considered for patients who have:

• Severe disease, e.g., hemorrhagic disease, confluent lesions, sepsis, encephalitis, or other conditions requiring hospitalization​;
• Lesions in aberrant locations, e.g., eyes, genitals, anus​; or
• At risk for severe disease, including patients who are immunocompromised (AIDS, transplant, etc.), pregnant or breastfeeding, children age <8 years​, or have atopic dermatitis, exfoliative skin conditions​, or one or more mpox complication​s.

Among the antiviral treatments with Expanded Access-Investigational New Drug (EA-IND) status available from the Strategic National Stockpile (SNS), tecovirimat is considered first-line treatment for mpox in both adults and children. Data on the effectiveness of tecovirimat for mpox in humans is limited. See the CDC’s guidance for using tecovirimat (CDC, https://www.cdc.gov/mpox/hcp/clinical-care/tecovirimat.html, Accessed 2025).

Overview of Tecovirimat

• FDA-approved for smallpox in adults and children in 2018. Based on efficacy in nonhuman primate (mpox) and rabbit (rabbitpox) models and safety established in a placebo-controlled trial involving 449 adults.
• Broadly active against orthopoxviruses (inhibits VP37)
• Resistance can develop with a single mutation
• Rebound infections may occur in shorter treatment courses (animal data)

Administration and Tolerability

• Weight-based dosing (PO or IV)
• Typical dose 600mg PO q12 hours (70kg person)​
• Optimal absorption when taken 30 min after fatty meal​
• Generally well-tolerated. Common adverse reactions include headache (12%), nausea (5%), abdominal pain (2%), and vomiting (2%). Neutropenia was found in one study participant. ​IV infusion has been associated with infusion site pain (73%), swelling (39%), and erythema (23%)​.
• Minimal drug-drug interactions​
• Repaglinide (hypoglycemia)​
• Midazolam (decreased effectiveness of midazolam)​
• HIV medications: may reduce levels of doravirine, rilpivirine, maraviroc, and rilpivirine – clinical significance is unclear​

Accessing Tecovirimat

• Tecovirimat is supplied through the Strategic National Stockpile via state and local health department​s. It is not available commercially. ​
• It is available under the CDC Expanded Access-Investigational New Drug (EA-IND) protocol. ​
• The EA-IND protocol allows healthcare providers to start treatment before the paperwork is submitted, however you must get informed consent prior to treatment).
• Learn more about obtaining tecovirimat (CDC, https://www.cdc.gov/poxvirus/monkeypox/clinicians/obtaining-tecovirimat.html, Accessed 9/30/2022).

Other therapeutics currently available from the Strategic National Stockpile as options for the treatment of mpox include Cidofovir, Brincidofovir, and Vaccinia Immune Globulin (VIGIV).

​

Mpox Vaccination

JYNNEOS and ACAM2000 are the two vaccines approved for the prevention mpox. JYNNEOS is the primary vaccine being used during this outbreak in the U.S.

Overview of JYNNEOS

• JYNNEOS is a replication-deficient Vaccinia virus​.
• It is administered as a series of two injections, 4 weeks apart​. Booster doses are recommended every 2 years for those with exposure to mpox.
• Side effects include injection site reactions; serious side effects are rare​.
• The effectiveness of the vaccine in the current outbreak is unknown​.

Who Should Get Vaccinated?

• Vaccination with JYNNEOS is recommended for people with known or confirmed exposures to mpox​. There are no efficacy data on post-exposure prophylaxis with JYNNEOS for the current outbreak, however vaccination may:​
  • Prevent disease if given within 4 days of exposure​
  • Reduce disease severity if given between 4-14 days of exposure
• People with presumed exposure to mpox​ should get the vaccine if they:
  • Know a sexual partner within the past 14 days was diagnosed with mpox​
  • Have had multiple sex partners in the past 14 days in an area with mpox​
• The vaccine can be given to people with HIV and immunocompromising conditions​.
• Recommended as pre-exposure prophylaxis for laboratory and other personnel with occupational exposure to orthopoxviruses​.

You should not get the JYNNEOS vaccine if you had a severe allergic reaction after a previous dose of JYNNEOS, or if you have a history of a serious reaction to the antibiotics gentamicin or ciprofloxacin, or chicken or egg protein.

• Administering the vaccine intradermally to people ≥ 18 years with no history of keloid scars increases vaccine supply ​

Vaccination for Healthcare Personnel​

Currently, pre-exposure prophylaxis is not recommended for healthcare personnel (HCP) with the exception of:​

• Clinical laboratory personnel who perform testing to diagnose orthopoxviruses, including those who use polymerase chain reaction (PCR) assays for diagnosis of orthopoxviruses, including Mpox virus​
• Research laboratory workers who directly handle cultures of  animals contaminated or infected with orthopoxviruses that infect humans, including Mpox virus, replication-competent Vaccinia virus, or recombinant Vaccinia viruses derived from replication-competent Vaccinia virus strains​
• Certain healthcare and public health response team members designated by public health authorities to be vaccinated for preparedness purposes​

Post-exposure prophylaxis may be indicated for specific high-risk exposures and on a case-by-case basis for intermediate risk exposures​, ideally administered 0-4 days after exposure; up until 14 days​.

Shift to Intradermal Dosing

The standard, FDA-approved regimen involves a subcutaneous injection of 0.5mL of the JYNNEOS vaccine. Subcutaneous administration continues to be authorized for people under 18 years of age.  

However, under an Emergency Use Authorization beginning August 9, 2022, the vaccine should be administered intradermally to people ≥ 18 years with no history of keloid scars in order to stretch the vaccine supply.

Watch the NETEC video demonstrating the technique of intradermal vaccine administration.