Monkeypox (FL INITIAL Autonomous Practice- Differential Diagnosis)

Monkeypox (MPX) is an endemic Orthopox virus in West and Central Africa. MPX is now occurring infrequently in other countries, causing healthcare concerns. Most human MPX infections are reported from the Congo Basin of the Democratic Republic of Congo (Hughes et al., 2021). MPX is most commonly found in rural, forested communities with poor sanitation and chronic malnutrition (Beer & Rao, 2019).

MPX cases are being reported sporadically around the world. It is believed to have spread worldwide due to the lack of immunization after the smallpox vaccine was stopped (Grant et al., 2020). Therefore, people who did not receive a smallpox vaccine (those younger than 40-50 years of age) may be susceptible.

MPX is categorized into 2 genetic clades. These include the genetic clades of West Africa and Central Africa (also called Congo Basin). These clades have epidemiological and clinical differences. The mortality rate of the West African clade is less than 1%, and there is no human-to-human transmission. The Central African clade is more frequent, can have a mortality of up to 11%, and has human-to-human transmission (Singh et al., 2021). Beer and Rao (2019) conducted a systematic review of the research published in English before August 15, 2018. They found an often-quoted 10% mortality rate. This rate came from early 1981-1986 data: 33 deaths out of 338. Data from the Democratic Republic of Congo (2001-2013) consistently reported mortality of <5%. Case fatality rate (CFR) from countries with the West African MPX were mostly 0%. The mortality for the Nigeria outbreak was 2.8%. Six deaths, 4 of whom were immunocompromised, out of 228 suspect cases. The mortality for 47 cases in United States outbreaks was 0%. No deaths have been reported from the April 2018 outbreak in Cameroon or the recent outbreak in the Central African Republic. In reports documenting the cause of death, people in high-risk groups comprised most of the deaths (Beer & Rao, 2019).

Because of inconsistencies in healthcare and surveillance systems in rural African settings, MPX data is incomplete and unreliable (Beer & Rao, 2019). This unreliable data is insufficient for statistical analysis (Beer & Rao, 2019). Due to the clinical overlap and insufficient laboratory availability, varicella-zoster virus (VZV) is often misdiagnosed as MPX, and the conditions may be co-infected in the same patient (Beer & Rao, 2019; Hughes et al., 2021). There is some suggestion that MPX is increasing in incidence. Data in more developed countries is more reliable.

Human-to-human spread is rare; however, cases have been recorded after prolonged, close exposure to infected Individuals (Beer & Rao, 2019; Singh et al., 2021; The Lancet, 2018). The transmission mechanisms are respiratory droplets, contact with body fluids, contaminated patient's environment or items, skin lesion of an infected person and sexual contact. Anal sex is one source of human-to-human transmission.

Animal-to-human transmission (zoonotic) occurs due to direct contact with the consumption of infected animals or direct contact with the blood, body fluids, and/or lesions of infected animals (The Lancet, 2018). Animals found to transmit MPX are rodents, rabbits, squirrels, monkeys, porcupines, and gazelles (Singh et al., 2021).

MPX is usually a self-limiting disease lasting 2 to 4 weeks (World Health Organization [WHO], 2022). The incubation period of MPX is usually 6 to 13 days but can range from 5 to 21 days. The invasion stage lasts up to 5 days. In this stage, symptoms are fever, intense headache, lymphadenopathy, back pain, myalgia, and intense asthenia (lack of energy).

Within 1–3 days of fever, the vesicular-pustular eruptions begin.

The number of lesions varies from a few to several thousand (WHO, 2022). The rash is more concentrated on the face and extremities than on the trunk. The rash affects the (WHO, 2022):

• Face (95% of cases)
• Palms of hands and soles of feet (75% of cases)
• Oral mucous membranes (70% of cases)
• Genitalia (30% of cases)
• Conjunctivae (20% of cases)

Lymphadenopathy is a distinctive feature of MPX compared to other rash-presenting differential diagnoses that may initially appear similar (Grant et al., 2020; WHO, 2022):

• Chickenpox
• Measles
• Smallpox
• Bacterial skin infections
• Scabies
• Syphilis
• Medication-associated allergies

VZV skin eruptions usually evolve over 24 hours instead of days, as seen with MPX, and are seen on the trunk more frequently than MPX (Singh et al., 2021). MPX has lesser eruptions than VZV or smallpox. Smallpox is five times more transmissible, has more nausea and vomiting, a less febrile stage before eruptions, more lesions, and a more profound systemic illness (Beer & Rao, 2019).

The polymerase chain reaction (PCR) laboratory test is recommended for accuracy and sensitivity. PCR can be used alone or in combination with sequencing. The recommended specimen type is skin lesion material, including swabs of lesion surface or exudate, roofs from more than one lesion, or lesion crusts. A biopsy is an option, but samples must be stored in a dry, sterile tube with no viral transport media and kept cold. PCR blood tests are usually inconclusive because of the short duration of viremia relative to the timing of specimen collection after symptoms begin and should not be routinely collected from patients (WHO, 2022).

Complications of MPX can include (WHO, 2022):

• Secondary infections
• Bronchopneumonia
• Sepsis
• Encephalitis
• Infection of the cornea with possible loss of vision

Bronchopneumonia occurrence is poorly understood, thought to be a secondary infection, and uncommon (Reynolds et al., 2017). MPX lesions on the cornea can lead to conjunctivitis, keratitis (inflammation of the cornea), or ulceration affecting vision. However, it is thought to be uncommon (Reynolds et al., 2017).

Hypoalbuminemia and low hematocrit, suggesting malnutrition, were found in patients hospitalized with MPX during the 2003 outbreak in the United States (Reynolds et al., 2017). This finding may be due to oral lesions and cervical lymphadenopathy. Malnutrition is a common problem that contributes to the severity of MPX patients in rural Africa (Reynolds et al., 2017).

There are no standard guidelines for the treatment of MPX at this time. Reynolds et al. (2017) recommend symptomatic support, fever, and pain management, measures to prevent secondary skin infection, adequate hydration and nutrition, protecting vulnerable anatomical locations such as the eyes, and managing complications. The skin and mucosal lesions require care. A serious rash can lead to dehydration, protein loss, and secondary infection. Focal inflammation of the lymphatic system and lung congestion can affect oxygenation and decrease food and fluid ingestion.

The European Medicines Agency licensed Tecovirimat, a smallpox antiviral for use in MPX (WHO, 2022). It is not widely available and should be monitored closely. Cidofovir has been proposed as a treatment in serious, dangerous cases. Cidofovir is a nucleotide analog that inhibits the production of herpes viruses (WHO, 2022).

Smallpox vaccination has been shown to be about 85% effective in preventing MPX or resulting in a milder illness, if it is not prevented (WHO, 2022). The Centers for Disease Control and Prevention (CDC) suggests a smallpox vaccine to be administered within fourteen days of exposure, though preferably within 4 days, for healthcare workers and others exposed to MPX cases. Vaccinia immune globulin (VIG) has not shown adequacy in treatment or prophylaxis. The Food and Drug Administration (FDA) supported a weakened, live, none-replicating smallpox and MPX antibody, Jynneos, for vaccination of adults at high-risk for smallpox or MPX exposure (Singh et al., 2021).

The WHO recommends contact and droplet precautions for MPX. The CDC's (2007) most recent recommendations for MPX are contact and airborne precautions.

1. Contact Precautions are used for patients with known or suspected infections or colonized with epidemiologically important microorganisms that can be transmitted by direct or indirect contact. The patient should be in a private room.
2. Standard Precautions should be used, and a gown and gloves should be worn if there is likely to be contact with the patient or environmental surfaces (Centers for Disease Control and Prevention [CDC], 2007).
3. Airborne Precautions are implemented for diseases transmitted by microorganisms carried by airborne droplet nuclei. Possibly infectious patients should be separated from others and asked to wear a surgical mask before airborne precautions can be provided. A surgical N95 respirator is recommended for Airborne Precautions. The N95 is a single-use, disposable item that must be fit-tested to be effective. Airborne Precautions also require the use of an airborne infection isolation room (AIIR) that has specially engineered airflow and ventilation systems. The door to the room must be kept closed, and the negative air pressure should be monitored. When the patient in airborne precautions has to be moved or transported, they should wear a surgical mask from when they leave the isolation room until they return (CDC, 2007).

Anyone who has been diagnosed with MPX, or suspects that they might have it, should avoid any close contact with other people. Once the rash sores scab over and fall off, the infected person is considered to be no longer contagious (CDC, 2022). Due to the fact that many cases have included sores in the genital and rectal areas among men who have sex with men, abstinence from sex when MPX is suspected is encouraged.

MPX is raising concern worldwide, but the case number is small, and transmission is not frequent. Symptom management is the best treatment at this point. Smallpox vaccination is recommended for exposure to MPX. Healthcare professionals need to be aware of the potential for MPX and how to identify it from differential diagnoses.

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• Centers for Disease Control and Prevention. (CDC). (2007). Guideline for isolation precautions: Preventing transmission of infectious agents in healthcare settings. Centers for Disease Control and Prevention (CDC). Visit Source.
• Centers for Disease Control and Prevention. (CDC). (2022). Monkepox clinical recognition. Centers for Disease Control and Prevention (CDC). Visit Source.
• Grant, R., Nguygen, L., & Breban, R. (2020). Modeling human-to-human transmission of monkeypox. Bulletin of the World Health Organization, 98(9), 638-640. Visit Source.
• Hughes, C., Liu, L., Davidson, W., Radford, K., Wilkins, K., Monroe, B., Metcalfe, M., Likafi, T., Lushima, R., Kabamba, J., Nguete, B., Malekani, J., Pukuta, E., Karhemere, S., Muyembe Tamfum, J., Okitolonda Wemakoy, E., Reynolds, M., Schmid, D., & McCollum, A. (2021). A tale of two viruses: Monkeypox and varicella zoster virus coinfections in the Democratic Republic of Congo. The American Journal of Tropical Medicine and Hygiene, 104(2), 604-611. Visit Source.
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• Reynolds, M., McCollum, A., Nguete, B., Shongo Lushima, R., & Petersen, B. (2017). Improving the care and treatment of monkeypox patients in low-resource settings: Applying evidence from contemporary biomedical and smallpox biodefense research. Viruses, 9(12), 380. Visit Source.
• Singh, N., Sharma, S., Ghai, G., & Singh, A. (2021). A systematic review on epidemiology of human monkeypox virus. Annals of the Romanian Society for Cell Biology, 25(7), 602-610. Visit Source.
• World Health Organization. (WHO). (2022). Monkeypox. World Health Organization (WHO). Visit Source.