Historical Monkeypox Clinical Presentation

Classically, monkeypox patients present with signs and symptoms resembling smallpox, a disease declared “globally eradicated” by the WHO in 1980. ⁷ The incubation period ranges from five to 21 days (typically between six to 13 days). The first signs and symptoms are constitutional and called a prodrome because they manifest before the rash. These include influenza-like illness (fever, chills, sore throat, cough, malaise, asthenia, diarrhea, nausea, and vomiting); ^{Reference Reynolds, Yorita and Kuehnert8} lymphadenopathy (a distinguishing feature from smallpox); and enanthem, often in the mouth and anus. Prodromal signs and symptoms typically precede the exanthem (rash) by one to four days. While the route of infection can influence clinical manifestations, ^{Reference Reynolds, Yorita and Kuehnert8} initial skin lesions in human ^{Reference Ogoina, Iroezindu and James9} and non-human primates ^{Reference Patrono, Pléh and Samuni10} often present in the anogenital region and then appear on the face, palms, and soles before spreading centrifugally. Skin lesions progress through macular, papular, vesicular (blister), and pustular stages, followed by scabbing and healing. In addition, lesions present in the same stage of development in a given body region. Long-term sequelae of monkeypox infection can include disfiguring scars ^{Reference Beer and Rao11} and permanent blindness resulting from corneal lesions. ^{Reference Hughes, McCollum and Pukuta12}

2022 Monkeypox Clinical Presentation

Unlike the classical monkeypox presentation, cases from the 2022 outbreak may not begin with a prodrome, skin lesions tend to be subdued, and lesions in a given body region may be at various stages of development. Furthermore, the constitutional symptoms can manifest simultaneously with the rash and enanthem. Moreover, lymphadenopathy and lesions on the palms and soles are less common. Hence, these features may have limited utility for differentiating monkeypox from other diseases. Monkeypox can appear similar to numerous more common diseases. The differential diagnosis of monkeypox is broad (Figure 2); thus, prehospital clinicians should have a low threshold for implementing monkeypox precautions.

Figure 2. Selected Agents in the Differential Diagnosis of Monkeypox.

Managing exposed persons in the 2022 outbreak can be challenging as the presentation may be subtle. Prehospital clinicians should consider monkeypox as a potential diagnosis in patients with risk factors for exposure because it can be infectious during a subclinical prodromal phase or before rash onset. Reducing monkeypox transmission helps avoid additional global stresses on the health care system. Strategies for reducing transmission include physical distancing, symptom monitoring, and standard hygienic practices. These approaches may obviate the need for quarantine of exposed health care workers, thereby contributing to preserving health care system capacity. ^{Reference Koenig, Marty and Beÿ13}

Patients seeking care may exhibit only prodromal symptoms or be unaware of their infectious skin lesions. The differential diagnosis varies based on vaccination status, prior exposure, virus clade, and disease stage. Monkeypox can resemble various dermatological conditions and sexually transmitted infections (STIs; Figure 3). ^{Reference Koenig, Beÿ and Marty14} Distinguishing between monkeypox and other more common diseases in the prehospital setting can be challenging. Detecting alternate infections, especially other STIs, does not exclude the possibility of monkeypox. Hospitalization for monkeypox is rare and usually results from the need to treat secondary infections or manage intractable pain emanating from lesions.

Figure 3. Selected Pathogens (Agents) in Monkeypox Differential Diagnosis.

Monkeypox virus is predominantly spread through close contact with infected skin lesions and can also be transmitted via bodily fluids and large droplets. Aerosolization of the virus (eg, from intubation, other medical procedures, or shaking contaminated bedsheets) can result in transmission to health care workers and others. Persons with confirmed monkeypox can mitigate transmission risk by covering infectious lesions, wearing a mask, and isolating themselves during the contagious period. Once lesions have healed, which can take two to four weeks or longer, they cease to be a source of infection.

Identify-Isolate-Inform (3I) Tool

The 3I framework was conceived in 2014 during the 2013-2016 Ebola virus outbreak when several Ebola cases presented at hospitals in the United States. The framework is designed to give clinicians high-level, actionable guidance for properly managing infectious diseases and has been applied to at least ten other conditions. ^{Reference Koenig15–Reference Koenig, Beÿ and McDonald23} Figure 1 presents a prehospital adaptation of the Monkeypox 3I Tool ^{Reference Koenig, Beÿ and Marty14} with specific considerations for EMS professionals.

Identify

Work is on-going to ascertain whether suspected or confirmed monkeypox patients can be identified at the emergency medical dispatch level. While travel history remains important in determining disease exposure risk, documented community spread in non-endemic regions has limited its usefulness. After emergency medical dispatchers identify a person with suspected or confirmed monkeypox, EMS professionals are advised to implement appropriate infection prevention measures before patient contact. These are similar to those applied during the COVID-19 pandemic and may include:

• Requesting the patient to mask and come to the door of the residence, bringing medications, if possible (allowing first responders to remain outside);

• If first responders must go inside to evaluate a patient, first send in a scout paramedic wearing full personal protective equipment (PPE);

• Apply a surgical mask to the patient for source control (if tolerated); and

• Avoid aerosol-generating procedures (AGPs).

If monkeypox is suspected, prehospital professionals should determine the patient’s likelihood of having the disease based on signs and symptoms and exposure risk. Cases in the 2022 outbreak are less likely to present with classical clinical indicators (Figure 4). Exposure risks independent of travel history include contact with persons or animal reservoirs suspected or confirmed to have monkeypox and contact with infected surfaces or other formites.

Figure 4. Classical Versus Monkeypox 2022 Presentations.

Isolate

Prehospital clinicians should don appropriate PPE throughout first contact, transport, care transfer, and during disinfection of the transport vehicle. Proper PPE includes an N95 respirator/equivalent (or higher), gloves, gown, eye protection, ²⁴ and shoe covers, if available. Notably, PPE used during the COVID-19 pandemic is sufficient to protect prehospital professionals from monkeypox. Source-control measures, including placing a surgical mask on the patient and covering exposed lesions, can lessen the risk of transmission in enclosed spaces (eg, the back of an ambulance). Similarly, avoid AGPs whenever possible because of the increased exposure risk and potential for infectious monkeypox virus aerosols to linger for extended periods in enclosed spaces. ^{Reference Verreault, Killeen, Redmann and Roy25}

Inform

It is imperative that transporting crews relay the patient’s suspected or confirmed monkeypox status to the receiving facility early to allow time for the hospital to prepare and minimize risks of infection spread and delays in the transfer of care. Local or state protocols may require prehospital clinicians to report communicable infectious diseases to their agency’s infection-control officer or health authority, especially for patients not transported to a hospital. Follow required protocols when reporting communicable diseases and health care worker exposures.