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Mpox

Mpox is a rare viral infection caused by an orthopoxvirus, which is a relatively large DNA virus that is related to smallpox. Mpox was originally named Monkeypox because it was discovered in a group of laboratory monkeys in 1958. Subsequently, rodents, and not monkeys, were found to be the most likely animal reservoir. Occasionally, mpox causes zoonotic infections in which animal-to-human transmission occurs by bite or scratch, bush meat preparation, or direct contact with body fluids. The first human case of mpox was reported n 1970 in the Democratic Republic of the Congo.

Human to human transmission occurs through direct contact with the infectious rash, scabs, or body fluids such as:

  • Close contact with blisters or lesions on the skin
  • Other body fluids such as respiratory droplets, after prolonged face to face contact
  • Indirect contact with fluid from blisters on contaminated clothing or linen.

A study published in Eurosurveillance detected high mpox DNA viral loads in saliva, rectal swabs, nasopharyngeal swabs, semen, urine, and feces. These results suggested the possibility of sexual transmission in addition to skin-to-skin contact. There have been no documented cases of transfusion-transmitted monkeypox infections.

The incubation period from infection to the appearance of symptoms ranges from 5 to 21 days. Patients infected with mpox typically experience a febrile prodrome that lasts 4 to 17 days after exposure. Symptoms include fever and chills, headache, muscle aches, malaise, and swollen lymph nodes. The prodrome is followed 1 to 4 days later by the onset of a vesicular or pustular rash that often begins on the face and then spreads to other parts of the body including the palms of the hand and soles of the feet. The rash progresses from flat to raised lesions, and eventually to fluid filled vesicles that rupture and scab over. Patients are considered to be infectious until all lesions have crusted over, crusts have separated, and healthy skin has formed under the crust. The case-fatality rate of mpox in Africa has ranged from 1% to 10%, with the highest risk of death among children.

Two distinct clades of mpox virus have been identified in the Congo Basin and in West Africa. Infections with the West African clade are generally self-limiting, and 99 percent of people completely recover. The Congo clade is more transmissible and virulent. The Congo Basin clade has a case-fatality rate of 10% while the West African clade has a case-fatality rate of 1%. 

In an average year, a few thousand cases occur in western and central Africa. Nigeria had an outbreak involving 450 people in 2017. In the past, cases outside Africa had been associated with travel to Africa or the importation of infected animals. The United States had an outbreak in 2003, when a shipment of rodents from Ghana spread the virus to pet prairie dogs in Illinois and infected more than 70 people.

Beginning in May 2022, the United Kingdom, Spain, and the United States detected an increasing number of cases of mpox among men who had sex with men (MSM). The men had not traveled to countries where the virus was endemic but did report sexual contact at common events. On May 23, 2022, the United States Centers for Disease Control and Prevention (CDC) activated an emergency outbreak response. The World Health Organization (WHO) declared a Public Health Emergency of International Concern on July 23, 2022.

As of May 10, 2023, the World Health Organization (WHO) had confirmed 87,314 global cases of mpox and 140 fatalities. Cases had been detected in 111 different countries, of which, 103 had not previously reported mpox. Ten countries reported the highest cumulative number of cases globally as of January 15, 2023, including Spain, Brazil, Germany, Canada, Mexico, Peru, the United Kingdom, Colombia, France, and the United States of America. On March 1, 2023, the WHO reported 110 confirmed mpox deaths.

As of May 10, 2023, CDC had confirmed 30,395 cases and 42 deaths in 52 United States jurisdictions. Sixty two pediatric cases have been reported in children 0-15 years old. Overall, 96.4% of cases have involved males and 3.6% females. Men between18 to 44 years old represented 79.2% of cases in the global outbreak. Among cases with known data on sexual orientation, 85.5% (27,217/31,834) identified as men who have sex with men. Among those with known HIV status 48.1% (17,268/35,914) were HIV-positive.

Patients have most frequently presented with a rash on the genitalia or surrounding area, indicating that transmission likely occurred during close physical contact during sexual activities. Other patients have experienced a single painful ulcer in their mouth, anus, or on their genitals. Some patients have developed severe disease, requiring hospitalization. These patients developed severe dermatologic manifestations, severe mucosal lesions. Some also had involvement of other organs such as the eyes, lungs, brain, and spinal cord.

On May 19, 2022, Portuguese researchers uploaded the first draft of a mpox virus genome that had been identified in their country. The preliminary data suggested that the virus was related to the West African clade. Genome sequencing results from virus recovered from the patient in Massachusetts closely resembled the Portugal genome and was related to the cases confirmed in the 2017–2018 outbreak in Nigeria.

This was the first time that chains of transmission had been reported in multiple countries without known epidemiological links to West or Central Africa, where this disease is endemic. These were also the first cases reported among men who have had sex with men. WHO’s outbreak bulletin stated, “The sudden and unexpected appearance of monkeypox simultaneously in several non-endemic countries suggests that there might have been undetected transmission for some unknown duration of time followed by recent amplifier events."

Mpox may have become more prevalent due to waning immunity in people who received the smallpox vaccine and no immunity in those who never received it because smallpox had been eradicated. The last smallpox vaccine was administered in the United States in 1972.

Timeline of Notable Events

On May 23, 2022, the United States Centers for Disease Control and Prevention (CDC) activated an emergency outbreak response.

On June 6, 2022, the Centers for Disease Control and Prevention (CDC) raised the mpox travel alert to level 2, warning Americans to practice enhanced precautions when traveling to both endemic and non-endemic countries that are experiencing mpox outbreaks. Enhanced precautions included avoiding contact with sick people, including genital contact, avoiding contact with dead or live animals, and avoiding contact with contaminated materials, such as bedding.

On June 28, the Centers for Disease Control and Prevention (CDC) activated its Emergency Operations Center (EOC) which increased access to testing and vaccination. Everyone with a presumed mpox exposure became eligible for a vaccine.

On July 23, 2022, The World Health Organization declared mpox a public health emergency of international concern (PHEOIC) because it was spreading around the world rapidly through new modes of transmission which were not fully understood.

On August 2, the White House announced the creation of a federal mpox response team that will coordinate efforts between the federal government and state and local authorities, including managing adequate supplies for testing, treating, and vaccinating.

On August 2, 2022, the Department of Health and Human Services (HHS) and the Food and Drug Administration (FDA) declared the ongoing mpox outbreak in the United States to be a public health emergency, paving the way for increased funding for tests, vaccines, and treatments.

On Friday, September 2, 2022, the Centers for Disease Control and Prevention (CDC) released a laboratory alert regarding rare false-negative results for the mpox virus that were obtained when using assays with the CDC's published primers and probes.

On November 2, 2022, the US Department of Health and Human Services (HHS) renewed the mpox public health emergency.

On Monday, November 28, 2022, the World Health Organization announced it was recommending mpox as the new name for monkeypox disease. Both names would be used simultaneously for 1 year while the monkeypox term was phased out. During the current outbreak, the name monkeypox had been associated with racism and stigmatism.

On January 31, 2023, The US Department of Health and Human Services (HHS) allowed the mpox public health emergency to expire because the number of cases had expired steadily since the peak in mid-August 2022. By the first weeks of January 2023, the United States was averaging just two new cases a day.

On February 15, 2023, the World Health Organization decided the mpox outbreak would remain a global public health emergency because 18 countries continued to report local transmission.

On May 11, 2023, the World Health Organization announced it would no longer classify mpox as a public health emergency of international concern, nearly a year after the virus emerged as a global threat.

Laboratory Testing

CDC recommended collection of two specimens, each from multiple lesions, preferably from different locations on the body and from lesions with differing appearances. Specimens are sent to a laboratory participating in the Laboratory Response Network (LRN) that has been validated to perform the non-variola Orthopoxvirus (NVO) assay. The NVO assay does not differentiate mpox virus from other Orthopoxviruses. If results are positive, the specimen is forwarded to CDC for further characterization by virus specific real-time PCR assay and genetic sequencing.

On June 22, the Department of Health and Human Services announced that five commercial laboratory companies were offering mpox testing using a CDC developed test. The five laboratories are Quest Diagnostics, LabCorp, Sonic, ARUP, and Mayo Clinic Laboratories. The five laboratories combined with the CDC’s Laboratory Response Network, have increased testing capacity to 80,000 specimens per week. 

On September 7, the Food and Drug Administration declared a public emergency requiring clinical laboratory tests for mpox to obtain emergency use authorization (EUA) before offering the test clinically.

Vaccination and Treatment

A positive test result for an Orthopoxvirus using the NVO assay is immediately actionable. Tecovirimat (TPOXX) can be prescribed as treatment for people with mpox, and two vaccines, JYNNEOS and ACAM2000 can be provided to close contacts as postexposure prophylaxis.

The first vaccine option is ACAM2000, which is the second generation of the smallpox vaccine that was named Dryvax. ACAM2000 was licensed in 2007 and stockpiled in case of a bioterrorism event. It is a replication-competent vaccine, which means it uses live vaccinia virus, which belongs to smallpox family. The vaccine is very effective because monkeypox is so closely related to smallpox.

A single dose is administered by a skin prick with a two-pronged needle that’s dipped into vaccine solution. Virus replicates at the injection site causing a red, itchy blister within 3 to 4 days that dries up forming a scab that falls off around week 3. This leaves a small scar. Unvaccinated people can be accidentally infected by someone who recently received the vaccine.

Jynneos is a much newer smallpox vaccine made by Bavarian Nordic that was licensed in 2019. It uses attenuated variola virus that is non-replicating. It is administered by intramuscular injection in two doses given 28 days apart. Recipients are not fully protected until 14 days after the second dose. Jynneos has been shown to be 85% effective in preventing mpox in humans. As of July 16, CDC recommends giving Jynneos vaccine within four days of exposure to prevent disease onset. It can be given later to reduce symptoms. The Department of Health and Human Services (HHS) has distributed 240,000 doses to the states. DHHS anticipates making approximately 1.9 million doses available in 2022 and another 2.2 million doses in the first half of 2023.

On August 10, 2022, the US Food and Drug Administration issued an emergency use authorization (EUA) that allowed healthcare workers to administer the Jynneos vaccine by intradermal injection to individuals 18 years of age and older who were determined to be at high risk for mpox infection. This change increased the total number of doses available for use by up to five-fold. On May 23, 2023, CDC reported that 1.2 million doses of the Jynneos mpox vaccine had been administered in the United States.

There are no Food and Drug Administration (FDA)–approved treatments for mpox. However, drugs that are approved for treatment of smallpox and cytomegalovirus might have activity against mpox virus. Tecovirimat (Tpocc) is an antiviral medication available in oral and intravenous formulations. Animal studies have shown that tecovirimat is effective in treating orthopoxvirus-induced disease. CDC recommended prescribing Tpoxx for patients with severe disease such as hemorrhagic disease, large number of confluent lesions, sepsis, encephalitis, and ocular or periorbital infections. Pregnant women and children over 8 years old should be offered treatment.

Healthcare Worker Precautions

Current CDC recommendations suggest HCWs wear a gown, gloves, eye protection, and an N95 (or higher-level) respirator while caring for patients who have suspected or confirmed mpox.

Blood Donation

On August 12, FDA reiterated that there had been no reports of transmission of mpox through blood transmission and that the risk of transfusion-transmission remained theoretical. Given the robustness of the existing safeguards for blood safety, it did not recommend that blood establishments ask donors additional, specific questions about possible exposure to mpox virus or screen blood donors FDA for monkeypox virus.

References

Kozlov M, Monkeypox goes global: why scientists are on alert. Nature News, May 20, 2022.

Soucheray, S. Officials confirm 226 monkeypox cases in 21 countries. CIDRAP News, may 25, 2022.

Alakunle E, Moens U, Nchinda G, Okeke MI. Monkeypox virus in Nigeria: infection biology, epidemiology, and evolution. Viruses. 2020;12(11):1257. doi:10.3390/v12111257

Bunge EM, Hoet B, Chen L, et al. The changing epidemiology of human monkeypox—A potential threat? A systematic review. PLoS Negl Trop Dis. 2022;16(2):e0010141. doi:10.1371/journal.pntd.0010141

Guagliardo SAJ, Monroe B, Moundjoa C, et al. Asymptomatic Orthopoxvirus Circulation in Humans in the Wake of a Monkeypox Outbreak among Chimpanzees in Cameroon. Am J Trop Med Hyg. 2020;102(1):206-212. doi:10.4269/ajtmh.19-0467

Kugelman JR, Johnston SC, Mulembakani PM, et al. Genomic variability of monkeypox virus among humans, Democratic Republic of the Congo. Emerg Infect Dis. 2014;20(2):232-239. doi:10.3201/eid2002.130118

McCollum AM, Damon IK. Human Monkeypox. Clin Infect Dis. 2014;58(2):260-267. doi:10.1093/cid/cit703

Nolen LD, Osadebe L, Katomba J, et al. Extended Human-to-Human Transmission during a Monkeypox Outbreak in the Democratic Republic of the Congo. Emerg Infect Dis. 2016;22(6):1014-1021. doi:10.3201/eid2206.150579

Patrono LV, Pléh K, Samuni L, et al. Monkeypox virus emergence in wild chimpanzees reveals distinct clinical outcomes and viral diversity. Nat Microbiol. 2020;5(7):955-965. doi:10.1038/s41564-020-0706-0

Petersen E, Kantele A, Koopmans M, et al. Human Monkeypox. Infect Dis Clin North Am. 2019;33(4):1027-1043. doi:10.1016/j.idc.2019.03.001

Russo AT, Berhanu A, Bigger CB, et al. Co-administration of tecovirimat and ACAM2000™ in non-human primates: Effect of tecovirimat treatment on ACAM2000 immunogenicity and efficacy versus lethal monkeypox virus challenge. Vaccine. 2020;38(3):644-654. doi:10.1016/j.vaccine.2019.10.049

Simpson K, Heymann D, Brown CS, et al. Human monkeypox—After 40 years, an unintended consequence of smallpox eradication. Vaccine. 2020;38(33):5077-5081. doi: 10.1016/j.vaccine.2020.04.06

Soucheray S. CDC raises travel alert level for monkeypox. CIDRAP News, June 07, 2022.

Jetelina K. Monkeypox Vaccine 101, July 1, 2022, This email address is being protected from spambots. You need JavaScript enabled to view it.

Peiro-Mestres A, et al. Frequent detection of monkeypox virus DNA in saliva, semen, and other clinical samples from 12 patients, Barcelona, Spain, May to June 2022, Eurosurveillance 2022;27: pii=2200503.https://doi.org/10.2807/1560-7917.ES.2022.27.28.2200503

O’Shea J, Filardo TD, Morris SB, Weiser J, Petersen B, Brooks JT. Interim Guidance for Prevention and Treatment of Monkeypox in Persons with HIV Infection — United States, August 2022. MMWR Morb Mortal Wkly Rep 2022;71:1023-1028. DOI: http://dx.doi.org/10.15585/mmwr.mm7132e4

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