Monkeypox Outbreak: Frequently Asked Questions

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The Society of Critical Care Medicine (SCCM) is monitoring cases of monkeypox in the United States, as well as multiple clusters elsewhere in North America and in Europe. While monkeypox is usually a self-limited disease with symptoms lasting two to four weeks, severe cases can occur, so it is important for critical care clinicians to recognize potential monkeypox infections. Visit SCCM’s monkeypox web page for additional details.

 

What is monkeypox?

• Monkeypox is a rare disease caused by infection with monkeypox virus.
• The virus belongs to the Orthopoxvirus genus in the family Poxviridae.
• The Orthopoxvirus genus also includes variola virus, which causes smallpox; vaccinia virus, derived from cowpox for preparing smallpox vaccines; and cowpox virus.
• Monkeypox is endemic to central and western Africa. It is a concern both as an emerging natural epidemic pathogen and because of possible man-made dispersal.
• In humans, it is most closely related to smallpox although, unlike smallpox, it has a wide range of hosts. Rodents and other mammals are likely reservoirs.¹
• Because it has multiple animal reservoirs, periodic outbreaks are likely.
• Previously considered a rare zoonosis, human monkeypox has reemerged as a clinically serious disease after decades of quiescence.
• There are two distinct strains of the virus. The Congo strain, which is more virulent, has historically killed up to 10% of those infected, while the West African strain causes fatality in 1% of cases.²

 

What is the epidemiology of monkeypox?

• Monkeypox was first discovered in 1958 when two outbreaks of a poxlike disease occurred in colonies of monkeys kept for research, hence the name monkeypox.
• The first human case of monkeypox was recorded in 1970 in the Democratic Republic of the Congo during a period of intensified effort to eliminate smallpox.
• A 2003 outbreak of monkeypox resulted from domestic prairie dogs housed next to rats imported from Ghana then distributed to areas around the United States, resulting in 81 probable and confirmed cases. There were no deaths, and most people had mild illness.^1,3
• Historical severity data are severely hampered by incomplete information, a clinical resemblance to chickenpox, lack of specific viral testing, and highly variable medical resource settings.
• Mortality rates in the 1970s ranged from 10% to 17%. The case fatality rate in West Africa was estimated at 3% to 4%. More recent surveillance studies have shown more than 10% mortality.⁴ The risk appears to be highest in children, young adults, and immunocompromised people.
• More confirmed cases of monkeypox have been diagnosed since 2016 than in the previous 40 years.⁵
• Since September 2017, Nigeria has continued to report sporadic cases of monkeypox, with a total of 502 cases and 8 deaths through October 2021.⁶
• Recently, cases have emerged in the United Kingdom, Europe, and North America, with evidence of local transmission.

 

How is monkeypox transmitted?

• The natural reservoir of monkeypox remains unknown. African rodents and nonhuman primates may harbor the virus and infect people.
• Transmission occurs when a person comes into contact with the virus from an animal, human, or material contaminated with the virus.
• The virus enters the body through broken skin (even breaks too small to be visible), the respiratory tract, or the mucous membranes of the eyes, nose, or mouth.
• Animal-to-human transmission can occur by bite or scratch, bush meat preparation, direct contact with body fluids or lesion material, or indirect contact with lesion material, such as through contaminated bedding.
• Human-to-human transmission is thought to occur primarily through large respiratory droplets with prolonged face-to-face contact. Other transmission methods include direct contact with body fluids or lesion material, and indirect contact with lesion material, such as through contaminated clothing or linens.

 

What are the clinical features of monkeypox?

• Most clinical data on human monkeypox are from investigations of outbreaks in central and western Africa.
• The incubation period is seven to 14 days, and the infectious period comprises the first week of the rash.
• Typically, there is a two-day prodrome before the development of rash, with nonspecific symptoms of fever, malaise, headache, and sometimes sore throat and cough.
• A characteristic lymphadenopathy occurs one to two days before the rash outbreak.
• More than 90% of patients develop lymphadenopathy but the distribution and laterality can be highly variable.
• Shortly after the prodrome, the rash appears. The monkeypox rash is usually centrifugal (predominantly occurring on the face and distal extremities and spreading inward).
• The rash progresses in the typical poxvirus fashion: papular, vesicular, pustular, and crust phases over a period of 14 to 21 days.
• The crust then sloughs off, leaving scars and dyspigmentation. The lesions remain infectious from the onset of rash and enanthema until they have scabbed over.
• Prior smallpox vaccination blunts the clinical features of monkeypox drastically, causing a much milder form of the disease with reduction of lymphadenopathy, rash severity, and distribution.

 

How is monkeypox diagnosed?

• Monkeypox should be suspected in any patient presenting with a new rash and lymphadenopathy, especially with recent travel to central or west Africa, parts of Europe where monkeypox has been reported, or in those with any known contacts for monkeypox.
• Some patients in the 2022 outbreak were noted to have the characteristic poxvirus rash in the genital or perianal region without fevers or other subjective symptoms.⁷
• If a monkeypox case is suspected, standard, contact, and airborne isolation should be immediately initiated, and the case should be reported to the CDC via the state health department.
• Personnel who collect specimens should use personal protective equipment (PPE) in accordance with recommendations for contact and droplet precautions.
• Real-time polymerase chain reaction can be used on lesion material to diagnose a monkeypox infection. The state health department and CDC should be consulted before collecting specimens.

 

How is monkeypox treated?

• Agents that could be beneficial in controlling a monkeypox outbreak include cidofovir, brincidofovir (previously known as CMX-001), tecovirimat (previously known as ST-246), vaccinia immune globulin (VIG), and vaccines.
• Data are not available on the effectiveness of cidofovir and brincidofovir in treating human cases of monkeypox, but both have proven activity against poxviruses in in vitro and animal studies.
• Cidofovir must be administered intravenously and carries a high risk of nephrotoxicity, requiring coadministration with oral probenecid to minimize this risk. Cidofovir administered at the time of, or immediately following, exposure has the potential to prevent monkeypox. Aerosolized cidofovir has been shown to protect mice against intranasal challenge with the cowpox virus.⁸
• Cidofovir was found to be superior to postexposure vaccination in a small animal study, showing drastically improved mortality to an intentional exposure.⁹
• Brincidofovir is an oral lipid conjugate derivative of cidofovir that was approved in the United States in 2021 for the treatment of smallpox in adult and pediatric patients, including neonates.
• Tecovirimat was approved in the United States in 2018 for the treatment of smallpox caused by variola virus in adult and pediatric patients. Studies using a variety of animal species have shown that tecovirimat is effective in treating orthopoxvirus-induced disease. Human clinical trials indicated that it was safe and tolerable with only minor side effects. Although currently stockpiled by the Strategic National Stockpile, tecovirimat is administered as an investigational new drug. It is approved in intravenous and oral forms.
• No data are available on VIG treatment of monkeypox, but it could have theoretical benefit. It has no proven benefit in the treatment of smallpox complications. It is unknown whether a person with severe monkeypox infection would benefit from treatment with VIG; however, its use may be considered in such instances.
• VIG can be considered for prophylactic use in an exposed person with severe immunodeficiency in T-cell function for which smallpox vaccination following exposure to monkeypox is contraindicated; however, no prior clinical experience is available to guide treatment. In a severe combined immunodeficient mouse model of vaccinia virus inoculation, it reduced mortality by 80%.¹⁰ These data are difficult to extrapolate to human use because the mice involved had no functional immune system.
• Other hospital treatment is supportive in nature.

 

Are there monkeypox vaccines?

• Because the monkeypox virus is closely related to the smallpox virus, the smallpox vaccine can protect against monkeypox. Past data from Africa suggest that smallpox vaccines are at least 85% effective in preventing monkeypox.¹
• Routine smallpox vaccination among the American public stopped in 1972 after the disease was eradicated in the United States and is currently not available to the general population.
• The U.S. military resumed vaccination against smallpox for deploying forces on December 13, 2002.¹¹
• JYNNEOS is FDA approved in the United States to prevent smallpox and monkeypox and can be administered preemptively for monkeypox exposure for people involved in monkeypox outbreak investigations.
• JYNNEOS is an attenuated, nonreplicating virus that is administered in two doses four weeks apart. The vaccine results in peak immunity about two weeks after the second dose.¹²
• The smallpox vaccine contains a live vaccinia virus. It is FDA approved for immunization in people aged 18 years and older and at high risk for smallpox infection. It can be administered to people exposed to monkeypox if used under an expanded access investigational new drug protocol.¹³
• The smallpox vaccine is administered with a bifurcated needle into the skin of the upper arm, resulting in a characteristic blister that then scabs over and eventually falls off. This lesion is infectious until the skin returns to its intact state. Therefore, individuals who receive smallpox vaccination must take precautions to prevent the spread of the vaccine virus.
• Based on the effectiveness of postexposure smallpox vaccine, the CDC advises postexposure prophylaxis to high-risk contacts within four days and up to 14 days of initial contact with monkeypox.
• Smallpox vaccination is recommended for military personnel and for laboratorians working with certain orthopoxviruses.
• Neither JYNNEOS nor the older smallpox vaccine is currently available to the public. They are available only to specific, high-risk populations.
• While widespread vaccination is unlikely, ring vaccination—the directed vaccination of those in direct contact with known cases—might be used. This strategy was used in prior smallpox outbreaks and is currently being adapted in the UK.
• Public health authorities are currently instructed to take stock of current vaccine availability, should a broader vaccination push be recommended.
• Fortunately, vaccination is durable and long-lasting. Smallpox vaccines historically have been known to provide immunity from smallpox with 95% efficacy for at least three to five years.

 

How is monkeypox prevented?

• Basic principles of infection control are warranted, including:
  • Rapid identification and isolation of the index patient based on travel history, contact, and clinical signs
  • Use of PPE by healthcare workers
  • Hospital systems approach of thorough contact tracing, including monitoring for secondary cases throughout the entire incubation period
• Once suspected, the state health department should be informed, followed by the CDC.
• Any healthcare worker who has cared for a patient with monkeypox should be alert for the development of symptoms that could suggest monkeypox infection, especially within the 21-day period after the last date of care, and should notify infection control, occupational health, and the health department for guidance about a medical evaluation.
• Vaccination may be effective as postexposure prophylaxis within the first four days after exposure.

 

What Clinicians Need to Know About Monkeypox in the United States and Other Countries: COCA Call on May 24, 2022

This Centers for Disease Control and Prevention (CDC) Clinician Outreach and Communication Activity (COCA) Call presented what clinicians need to know about monkeypox, including guidance about the typical clinical presentation, treatment options, pre- and postexposure prophylaxis, and reporting to public health authorities.
 
 

 References

1. Di Giulio DB, Eckburg PB. Human monkeypox: an emerging zoonosis. Lancet Infect Dis. 2004 Jan;4(1):15-25.
2. McCollum A, Damon IK. Human monkeypox. Clin Infect Dis. 2014 Jan;58(2):260-267..
3. Centers for Disease Control and Prevention. Update: multistate outbreak of monkeypox: Illinois, Indiana, Kansas, Missouri, Ohio, and Wisconsin, 2003. MMWR Morb Mortal Wkly Rep. 2003 Jun 20;52(24):561-564.
4. Petersen E, Abubakar I, Ihekweazu C, et al. Monkeypox: enhancing public health preparedness for an emerging lethal human zoonotic epidemic threat in the wake of the smallpox post-eradication era. Int J Infect Dis.2019 Jan;78:78-84.
5. Durski KN, McCollum AM, Nakazawa Y, et al. Emergence of monkeypox: West and Central Africa, 1970-2017. MMWR Morb Mortal Wkly Rep. 2018 Mar 16;67(10):306-310.
6. Nigeria Centre for Disease Control (NCDC). Situation report. Update on monkeypox (MPX) in Nigeria. October 31, 2021. Accessed May 31, 2022.  https://ncdc.gov.ng/themes/common/files/sitreps/75e3b8532d48167c0e58fcd0eca03062.pdf
7. Centers for Disease Control and Prevention. U.S. monkeypox 2022: situation summary. Page last reviewed May 30, 2022. Accessed May 31, 2022. https://www.cdc.gov/poxvirus/monkeypox/outbreak/current.html
8. Roy CJ, Baker R, Washburn K, Bray M. Aerosolized cidofovir is retained in the respiratory tract and protects mice against intranasal cowpox virus challenge. Antimicrob Agents Chemother. 2003 Sep;47(9):2933-2937.
9. Stittelaar K, Neyts J, Naesens L, et al. Antiviral treatment is more effective than smallpox vaccination upon lethal monkeypox virus infection. Nature. 2006 Feb 9;439(7077):745-748.
10. Shearer JD, Siemann L, Gerkovich M, House RV. Biological activity of an intravenous preparation of human vaccinia immune globulin in mouse models of vaccinia virus infection. Antimicrob Agents Chemother. 2005 Jul;49(7):2634-2641.
11. Grabenstein JD, Winkenwerder Jr, W. US military smallpox vaccination program experience. JAMA. 2003 Jun25;289(24):3278-3282.
12. JYNNEOS. Prescribing information. Bavarian Nordic. June 2021. Accessed May 31, 2022. https://www.fda.gov/media/131078/download
13. Centers for Disease Control and Prevention. Monkeypox. Treatment. Page last reviewed July 17, 2021. Accessed May 31, 2022 https://www.cdc.gov/poxvirus/monkeypox/clinicians/treatment.html

 

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Posted: 5/31/2022 | 0 comments