Following the global COVID-19 emergency, another public health emergency was declared by the World Health Organization on July 23, 2022: “monkeypox.” Monkeypox virus (MPXV) belongs to the Poxviridae family and causes monkeypox, a disease clinically similar to smallpox.[1,2] Monkeypox was discovered in 1958 after two outbreaks of poxlike disease in research colonies of monkeys. The first known human infection was in 1970 in a newborn in the Democratic Republic of Congo. Monkeypox began to reemerge in 2022, and the evolution of the outbreak is worrisome, as it does not seem that the pandemic, which has affected large numbers of people worldwide, is slowing down significantly. Nature reported more than 57,000 cases and approximately 22 deaths on September 13. Animal-to-human and human-to-human transmissions are two possible routes of transmission for MPXV. According to the clinicians, intimate sexual contact was the suspected route of transmission for the MPXV in 95% of cases. Homosexual or bisexual men, as well as other men who have sex with men, have been particularly hard hit by the current outbreak. Compared with smallpox, symptoms are similar but less severe and include pustular skin lesions, fever, headache, myalgia, and lymphadenopathy. The rash usually begins on the lips and spreads to the face and then to the limbs in a circular pattern.
According to the Centers of Disease Control and Prevention, MPXV infection can be prevented by taking certain measures, such as avoiding contact with a person who has a rash that looks like monkeypox, avoiding contact with materials that MPXV-infected people have touched, avoiding contact with animals, and washing hands. Besides these precautions, the World Health Organization and the Centers of Disease Control and Prevention have recommended vaccination as the most important measure to control the progression of the disease. Although there are no specific vaccines against MPXV, many previous studies conducted after smallpox infections have shown that smallpox immunization is 85% effective against MPXV.
2. Available vaccines and their efficacy
Three vaccines for pre-exposure prophylaxis against orthopoxvirus infection in at-risk individuals are now available: ACAM2000, JYNNEOS, and LC16m8. JYNNEOS (Bavarian Nordic), a newer-generation smallpox vaccine, has been approved by the Food and Drug Administration in the United States and Europe to protect against monkeypox, and the earlier generation ACAM2000 can be administered off-label for the same reason. Prophylactic vaccination administered as soon as possible after a likely exposure can prevent or dramatically reduce infections. If smallpox vaccination is not available, vaccinia immune globulin can be used as a substitute for postexposure prophylaxis in persons with severely reduced cellular immunity.
ACAM2000, a live vaccine virus preparation, was injected by pricking the skin surface. After successful injection, a lesion (also referred to as a “take”) appeared at the injection site. This injection lesion-growing virus can spread to other parts of the body or other people. People who receive the ACAM2000 vaccine must exercise caution to prevent the spread of the virus and are considered immunized after 28 days. Another vaccine is a nonreplicating live virus called JYNNEOS. Two subcutaneous injections were given 4 weeks apart. There is no obvious “take,” meaning there is no possibility of the infection spreading to other areas of the body or other people. Two weeks after receiving the second dose of the vaccine, JYNNEOS recipients were considered unimmunized. A third-generation vaccine developed by KM Biologics is the LC16m8 vaccine. It was developed and licensed in Japan in 1975 for use against smallpox. In 2014, it was licensed for use against monkeypox in the United States. It was produced using cell culture techniques and is a live, low-multiplication vaccine. The Lister strain with a deletion mutation in the viral protein produces LC16m8. All age groups, including neonates and children, received multidose vaccine percutaneously with a needle with two ends. Because of the short supply of vaccines in some places, vaccination is recommended only for those who have been in contact with a person infected with monkeypox. This included people who knew a sexual partner who had received a monkeypox diagnosis within the past 14 days, persons who have visited a place or event where there was known exposure to monkeypox, and people who had more than one sexual partner in the previous 14 days, including gay, bisexual, transgender, and other men who had had sex with men.
The smallpox vaccine also protects the population from monkeypox because the viruses that cause monkeypox and smallpox are closely related. Clinical studies on the immunogenicity of JYNNEOS and efficacy information from animal studies indicate that JYNNEOS is effective against monkeypox. A study has also shown that the risk of human monkeypox is inversely related to smallpox immunization based on our active surveillance. Before the end of official immunization efforts in 1980, those who were vaccinated had a 5.21-fold lower risk of infection than those who were not vaccinated.
3. Adverse effects of vaccines and precautions
The ACAM200, JYNNEOS, and LC16m8 vaccines provide safety against MPXV, but at the same time, different risk factors are associated with each vaccine. ACAM2000, a second-generation vaccine, is not recommended in patients suffering from allergic skin reactions such as dermatitis, eczema, or other pathogenic conditions (eg, herpes simplex virus infection, acne, or varicella zoster virus).[8,9] Moreover, leukemia, lymphoma, and AIDS are some examples of diseases associated with immunosuppression for which ACAM2000 is contraindicated. It is also not advisable for pregnant women and infants. Common adverse effects include lymphadenitis, other symptoms (myalgia, fever, and fatigue), and injection site reactions. Furthermore, skin infections, erythema multiforme, and Stevens-Johnson syndrome are among the adverse effects associated with this vaccine. The most common and frequent infection associated with ACAM2000 is infection of the conjunctiva and eyelid. However, other body sites such as the genitals, anus, mouth, and lips are equally susceptible.
Reactions at the injection site and physical symptoms such as redness, pain, inflammation, itching, and induration are some of the most common adverse effects of JYNNEOS. Systemic symptoms associated with this vaccine include muscle soreness, headache, fatigue, nausea, and myalgia. No potential risk of myopericarditis associated with this vaccine has been identified.
Furthermore, people who are immunocompromised, have atopic dermatitis, are pregnant, or have an adverse reaction to a vaccine component should take LC16m8 vaccine with caution. Lymphadenopathy, fatigue, redness, and swelling at the injection site are minor adverse effects. However, no significant adverse effects associated with LC16m8 have been reported.[8,12]
The recent COVID-19 pandemic has had a severe impact on the economies of affected countries. Developing countries, in particular, are struggling to get their finances and health systems under control, leaving them unprepared for another pandemic. Our joint response to this monkeypox outbreak and other future outbreaks should be based on the lessons learned from the COVID-19 pandemic. Although the available vaccines against MPXV are somewhat effective, unlike many other vaccines, they have certain downsides. Therefore, we should pay more attention to the immunization of those who have been in contact with infected individuals. Health professionals should develop appropriate instructions and take preventive measures, including personal cleanliness. It is also important to ensure that the hospital has beds, ventilators, and properly trained staff, to name a few of the most important requirements. All people should have the opportunity to avail themselves of these tests. Educating physicians about the symptoms and signs of MPXV infection is important. To stop the spread of this contagious disease, the public should be made aware of quarantine, and hospitals should have well-equipped quarantine stations to isolate patients immediately. Surveillance of patients' family members is also necessary. Airport screening is also mandatory. Adequate precautions must be taken to prevent the transmission of the MPXV.
In addition, the public health surveillance and epidemiological analysis need to be more accurately quantified, as well as to improve the safety of monkeypox vaccines, conduct further clinical studies, and monitor drug safety in vulnerable populations. The development of a novel vaccine against MPXV that is safe, effective, and virtually free of adverse effects is necessary. It is even more important that the international community should work together to ensure widespread vaccine access and effective communication, raise public awareness and community outreach strategies, and focus MPXV vaccination coverage on the most vulnerable populations and areas where outbreaks are occurring.
Conflicts of Interest
1. Awan MAE, Waseem M, Sahito AF, et al. Monkeypox has devastated the world; should we prepare for the outbreak of a new pandemic?Ann Med Surg 2022;79:104051. doi: 10.1016/j.amsu.2022.104051.
2. Khatri G, Khattak ZE, Butt MH, et al. Monkeypox is not a sexually transmitted disease: a public health concern and avoidance of myths. Disaster Med Public Health Prep 2022;1–2. doi: 10.1017/dmp.2022.237.
3. Breman JG, Kalisa-Ruti, Steniowski MV, et al. Human monkeypox, 1970–79. Bull World Health Organ 1980;58(2):165.
4. Kozlov M. How deadly is monkeypox? What scientists know. Nature 2022;609(7928):663. doi: 10.1038/d41586-022-02931-1.
5. Centers for Disease Control and Prevention. How to protect yourself. Available from: https://www.cdc.gov/poxvirus/monkeypox/prevention/protect-yourself.html
. Accessed November 12, 2022.
6. Mandell GL, Bennett JE, Dolin R. Mandell, Douglas, and Bennett's principles and practice of infectious and diseases. Available from: https://www.us.elsevierhealth.com/mandell-douglas-and-bennetts-principles-and-practice-of-infectious-diseases-9780323482554.html
. Accessed August 8, 2022.
7. Centers for Disease Control and Prevention. Interim clinical considerations for use of JYNNEOS and ACAM2000 vaccines during the 2022 U.S. monkeypox outbreak. Available from: https://www.cdc.gov/poxvirus/monkeypox/clinicians/smallpox-vaccine.html
. Accessed August 8, 2022.
8. World Health Organization. Vaccines and immunization for monkeypox: interim guidance, 14 June 2022. Available from: https://www.who.int/publications/i/item/who-mpx-immunization-2022.1
. Accessed August 8, 2022.
9. Rimoin AW, Mulembakani PM, Johnston SC, et al. Major increase in human monkeypox incidence 30 years after smallpox vaccination campaigns cease in the Democratic Republic of Congo. Proc Natl Acad Sci U S A 2010;107(37):16262–16267. doi: 10.1073/pnas.1005769107.
10. Petersen BW, Harms TJ, Reynolds MG, et al. Use of vaccinia virus smallpox vaccine in laboratory and health care personnel at risk for occupational exposure to orthopoxviruses—recommendations of the Advisory Committee on Immunization Practices (ACIP), 2015. MMWR Morb Mortal Wkly Rep 2016;65(10):257–262. doi: 10.15585/mmwr.mm6510a2.
11. Rao AK, Petersen BW, Whitehill F, 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;71(22):734–742. doi: 10.15585/mmwr.mm7122e1.
12. Center for Infectious Disease Research and Policy. FDA approves Acambis smallpox vaccine. Available from: https://www.cidrap.umn.edu/news-perspective/2007/09/fda-approves-acambis-smallpox-vaccine
. Accessed August 8, 2022.