Monkeypox Update July 2022
Monkeypox is a rare viral infection caused by an orthopoxvirus, which is a relatively large DNA virus that is related to smallpox. Monkeypox received its name because it was discovered in a group of laboratory monkeys in 1958. However, rodents, and not monkeys, are the most likely animal reservoir. Occasionally, monkeypox causes zoonotic infections in which animal-to-human transmission occurs by bite or scratch, bush meat preparation, or direct contact with body fluids.
Human to human transmission is thought to spread primarily through respiratory droplets, direct contact with skin lesions or bodily fluids, or indirect contact via contaminated clothing or linens. The incubation period from infection to the appearance of symptoms ranges from 5 to 21 days.
Patients infected with monkeypox typically experience a febrile prodrome 4 to 17 days after exposure. Symptoms include fever and chills, headache, muscle aches, swollen lymph nodes, and a rash like chickenpox. The prodrome is followed 1 to 4 days later by the onset of a vesicular or pustular rash with a centrifugal distribution. The rash develops 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 monkeypox in Africa ranges from 1% to 10%, with the highest risk of death among children.
Two distinct clades of monkeypox virus have been identified in the Congo Basin and in West Africa. 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%. Nigeria had an outbreak involving 450 people in 2017.
In an average year, a few thousand cases occur in western and central Africa. But cases outside Africa have been limited to a handful that are associated with travel to Africa or with 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.
Recently, public health experts have become concerned about simultaneous outbreaks of monkeypox in 59 countries. On July 8, 2022, the global total number of cases was 8,127. On June, 30, The European Centre for Disease Prevention and Control and the World Health Organization European regional reported 4,177 monkeypox cases in Europe with the United Kingdom producing 25% of those cases. Germany had 838 cases, Spain 736 cases, Portugal 365 cases, and France 350 cases. CDC has confirmed 605 cases in 34 states, Washington D.C, and Puerto Rico. The World Health Organization African regional office reported that Africa had 1,821 cases in 13 countries. So far none of the cases in non-endemic countries has been fatal.
Public health agencies have reported that most cases have involved men between the ages of 20 and 50 who have had sexual contact with other men and had no travel history to countries where monkeypox was endemic. Patients have frequently presented with a rash on the genitalia or surrounding area, indicating that transmission likely occurred during close physical contact during sexual activities. Monkeypox is not a sexually transmitted disease that is transmitted through seminal fluid or vaginal secretion. Most cases have been mild.
On May 19, Portuguese researchers uploaded the first draft of a monkeypox virus genome that had been identified in their country. The preliminary data suggests that the virus is related to the West African clade. Genome sequencing results from virus recovered from the patient in Massachusetts closely resembled the Portugal genome and is related to the cases confirmed in the 2017–2018 outbreak in Nigeria.
This is the first time that chains of transmission have been reported in multiple countries without known epidemiological links to West or Central Africa, where this disease is endemic. These are 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."
Monkeypox may 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.
On June 6, 2022, the Centers for Disease Control and Prevention (CDC) raised the monkeypox travel alert to level 2, warning Americans to practice enhanced precautions when traveling to both endemic and non-endemic countries that are experiencing monkeypox 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.
CDC recommends 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 Monkeypox 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.
Treatment is the same for all NVO infections. Thus, a positive test result for an Orthopoxvirus using the NVO assay is immediately actionable. Tecovirimat (TPOXX) can be prescribed as treatment for people with monkeypox, and two vaccines, JYNNEOS and ACAM2000 can be provided to close contacts as postexposure prophylaxis.
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 monkeypox exposure became eligible for a vaccine.
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 four weeks apart. has been shown to be 85% effective in preventing monkeypox in humans. The Department of Health and Human Services (HHS) has 56,00 doses in stock and has ordered 750,000 more doses. CDC recommends giving Jynneos vaccine within four days of exposure to prevent disease onset. It can be given later to reduce symptoms.
Roche Diagnostics announced it has developed a polymerase chain reaction (PCR) test kit that detects orthopoxviruses, including all monkeypox viruses from both the West African and Central African clades.
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.
Other Resources
Center for Health Security Monkeypox Fact Sheet
WHO Monkeypox Epidemiology, Preparedness and Response Course
