Guideline sources The following summarized guidelines for the evaluation and management of monkeypox virus infection are prepared by our editorial team based on guidelines from the World Health Organization (WHO 2022) and the Center for Disease Control (CDC 2022; 2021; 2019). 1 2 3 4 5 6 Guidelines 1. Screening and diagnosis Epidemiology: view one case of monkeypox virus infection as an outbreak. E Show 3 more Case definition: Define suspected case as a patient meeting all of the following criteria: a patient of any age presenting in a monkeypox non-endemic country with an unexplained acute rash 1 of the following signs or symptoms, since 15 March 2022: headache, acute onset of fever (> 38.5 C), lymphadenopathy, myalgia, back pain, profound weakness https://web.pathway.md/diseases/recNf8AEVbBSLUO9x 1/6 6/30/23, 1:05 AM Monkeypox virus infection Pathway the following common causes of acute rash do not explain the clinical picture: varicella zoster, herpes zoster, measles, herpes simplex, bacterial skin infections, disseminated gonococcal infection, primary or secondary syphilis, chancroid, lymphogranuloma venereum, granuloma inguinale, molluscum contagiosum, allergic reaction (such as to plants) and any other locally relevant common causes of papular or vesicular rash. E Show 7 more Indications for testing: Obtain testing for monkeypox virus infection in any patient meeting the definition for a suspected case. E Decide on testing based on both clinical and epidemiological factors, linked to an assessment of the likelihood of infection. E Differential diagnosis: Take into account other potential causes of discrete skin lesions or a disseminated rash with the following as examples of other etiologies for similar-appearing skin lesions at the different stages of development: HSV VZV molluscum contagiosum virus enterovirus measles scabies treponema pallidum bacterial skin infections medication allergies parapoxviruses (causing orf and related conditions) chancroid. E Recognize that it can be challenging to differentiate monkeypox solely based on the clinical presentation, particularly in cases with an atypical presentation, due to the range of conditions causing skin rashes and because clinical presentation may more often be atypical during this outbreak. E 2. Diagnostic investigations Initial evaluation: Obtain the following in patients with monkeypox virus infection: clinical examination using appropriate infection prevention and control measures asking about possible sources of infection and the presence of similar illnesses in the patient's community and contacts (both backward to identify the source and forward contact tracing to reduce onward transmission) collecting and dispatching specimens for monkeypox laboratory examination. E Show 4 more https://web.pathway.md/diseases/recNf8AEVbBSLUO9x 2/6 6/30/23, 1:05 AM Monkeypox virus infection Pathway Specimen collection: As per CDC 2022 guidelines, collect specimens only after appropriate consultations. E Show 3 more As per WHO 2022 guidelines, sample skin lesion material, including swabs of lesion surface and/or exudate, roofs from > 1 lesion or lesion crusts, as the type of specimen for laboratory confirmation of monkeypox. E Show 5 more Specimen handling: As per CDC 2022 guidelines, ensure adequate labeling clearly distinguishing specimens from patients with suspected monkeypox. E As per WHO 2022 guidelines, store specimens refrigerated or frozen within an hour of collection and transport them to the laboratory as soon as possible after collection. Ensure correct handling and storage of specimens during transportation for accurate diagnostic testing. E Show 6 more Laboratory testing, safety measures: As per CDC 2022 guidelines, use personal protective equipment in accordance with recommendations for standard, contact, and droplet precautions when collecting specimens from patients with suspected monkeypox virus infection. E As per WHO 2022 guidelines, ensure the use of adequate standard operating procedures and train laboratory personnel for appropriate donning and doffing of personal protective equipment, specimen collection, storage, packaging, and transport. Regard all specimens collected for laboratory investigations as potentially infectious and handle them with caution. Take measures to minimize the risk of laboratory transmission based on risk assessment when testing routine clinical specimens from patients with confirmed or suspected monkeypox, including: limiting the number of staff testing specimens only to staff with proven competency wearing appropriate personal protective equipment using rigorously applied standard precautions avoiding any procedures that could generate infectious aerosols. E Show 7 more As per WHO 2022 guidelines, handle samples taken from patients with suspected monkeypox virus infection by trained healthcare workers in suitably equipped laboratories. E Show 2 more Laboratory testing, NAAT: As per CDC 2022 guidelines, consider obtaining a real-time PCR on lesion material to diagnose a potential monkeypox virus infection. Consult with the state health department and the national CDC before collecting specimens. E As per WHO 2022 guidelines, obtain testing for the presence of monkeypox virus in appropriately equipped laboratories by staff trained in the relevant technical and safety procedures. E https://web.pathway.md/diseases/recNf8AEVbBSLUO9x 3/6 6/30/23, 1:05 AM Monkeypox virus infection Pathway Show 7 more Laboratory testing (serology): do not use serum antibody detection alone for the diagnosis of monkeypox. D Show 3 more Laboratory testing (electron microscopy): consider using electron microscopy to evaluate the sample for a potential poxvirus but do not routinely for the diagnosis of poxviruses because of the availability of molecular assays and the high technical skills and facility required. E Laboratory testing (viral culture): do not obtain virus isolation as a routine diagnostic procedure. Perform virus isolation, if obtained, in laboratories with appropriate experience and containment facilities. D Laboratory testing (interpretation): take into account clinical and epidemiological data for confirmation of monkeypox virus infection. E Show 2 more 3. Medical management Specific treatment: recognize that at this time there are no specific treatments available for monkeypox infection, but monkeypox outbreaks can be controlled using the smallpox vaccine, cidofovir, tecovirimat, and vaccinia immune globulin. E Show 4 more 4. Preventative measures Vaccination in high-risk groups: As per CDC 2022 guidelines, administer pre-exposure prophylaxis against orthopoxviruses with either JYNNEOS or ACAM2000 in persons at risk for occupational exposure to orthopoxviruses (such as research laboratory personnel working with orthopoxviruses, clinical laboratory personnel performing diagnostic testing for orthopoxviruses, designated response team members, and healthcare personnel administering ACAM2000 or caring for patients infected with orthopoxviruses). E Show 3 more As per WHO 2022 guidelines, conduct a risk assessment to assess whether arranging immunization for healthcare workers, including laboratory personnel and other staff at risk of exposure to individuals or specimens with monkeypox virus is required, as various smallpox vaccines, containing vaccinia virus, provide cross-protection against other orthopoxviruses, including monkeypox. E Show 2 more Post-exposure vaccination: As per WHO 2022 guidelines, consider offering post-exposure vaccination (ideally within 4 days of exposure) for higher risk contacts, such as healthcare workers including laboratory personnel. https://web.pathway.md/diseases/recNf8AEVbBSLUO9x 4/6 6/30/23, 1:05 AM Monkeypox virus infection Pathway E As per CDC 2019 guidelines: Administer smallpox vaccine within 4 days from the date of exposure in order to prevent the onset of the disease. Recognize that vaccination may reduce the symptoms of disease, but may not prevent the disease if administered between 4-14 days after the date of exposure. E Consider offering vaccination in persons exposed to the monkeypox virus and not received the smallpox vaccine within the last 3 years. E 5. Follow-up and surveillance Contact tracing: initiate contact tracing to control the spread of the monkeypox virus to allow the interruption of transmission and help people at a higher risk of developing severe disease to more quickly identify their exposure. Interview case-patients to elicit the names and contact information of all such persons. Notify contacts within 24 hours of identification. E Show 12 more 6. Quality improvement Networking and reporting: As per CDC 2022 guidelines: Report possible human cases of monkeypox to the local hospital epidemiologist and/or infection control personnel, the state health department, and the national center for disease control and prevention. E Consult with the state epidemiologist, state health laboratory, and the national center for disease control and prevention before sending specimens to the center for disease control and prevention. E As per WHO 2022 guidelines: Ensure access to timely and accurate laboratory testing of suspected samples, either nationally or through referral to laboratories in other countries willing and able to perform orthopoxvirus or monkeypoxvirus diagnosis. E Consider inactivating samples in the local laboratory, where appropriate and safely performed, to facilitate referral and ease logistical challenges. E As per WHO 2022 guidelines, report suspected cases immediately to national or local public health authorities. Report probable and confirmed cases immediately to the WHO through the International Health Regulations national focal points under the International Health Regulations. Notify the WHO immediately about laboratory-confirmed cases. E Show 2 more Clinical findings https://web.pathway.md/diseases/recNf8AEVbBSLUO9x 5/6 6/30/23, 1:05 AM Monkeypox virus infection Pathway Symptoms Ocular exam Back pain Conjunctival injection Chills Integument exam Cough Fever Maculopapular rash Headache Petechiae Malaise Skin wounds Myalgia Vesiculopustular rash Skin rash Sore throat Lymphatic exam Axillary lymphadenopathy Cervical lymphadenopathy Inguinal lymphadenopathy Lymphadenopathy Submandibular lymphadenopathy References 1. No authors listed. Surveillance, case investigation and contact tracing for Monkeypox. WHO, 2022. Open 2. No authors listed. Laboratory testing for the monkeypox virus: Interim guidance. WHO, 2022. Open 3. Centers for Disease Control and Prevention. Monkeypox: Preparation and Collection of Specimens. CDC. 2022 May 18. Open 4. Centers for Disease Control and Prevention. Monkeypox: Monkeypox and Smallpox Vaccine Guidance. CDC. 2019 Dec 2. Open 5. Centers for Disease Control and Prevention. Monkeypox: Treatment. CDC. 2021 July 17. Open 6. Agam K Rao, Brett W Petersen, Florence Whitehill et al. Use of JYNNEOS Smallpox and Monkeypox Vaccine, Live, Nonreplicating) for Preexposure Vaccination of Persons at Risk for Occupational Exposure to Orthopoxviruses: Recommendations of the Advisory Committee on Immunization Practices United States, 2022. MMWR Morb Mortal Wkly Rep. 2022 Jun 3;71 22 734 742. Open https://web.pathway.md/diseases/recNf8AEVbBSLUO9x 6/6