The Paper's reporter Sen Ning
Halfway through June, the number of confirmed monkeypox infections worldwide has rapidly exceeded 2,000. The unprecedented expansion of the monkeypox virus has led the World Health Organization (WHO) to implement a series of new emergency actions to respond to the outbreak, including the announcement that an emergency meeting will be held next week to assess the severity of the outbreak and the release of new monkeypox vaccination guidelines.
At the same time, Countries most affected by the monkeypox epidemic, such as Europe and the United States, have increased the procurement of monkeypox vaccines, looking forward to controlling the spread of the epidemic through vaccination. But WHO still warns that the decision to use smallpox or monkeypox vaccines should be based on a comprehensive assessment of the risks and benefits.
According to the U.S. Centers for Disease Control and Prevention, as of June 16, the number of confirmed monkeypox cases worldwide reached 2,027, coming from more than 40 countries that have never had monkeypox. Monkeypox infections often cause flu-like symptoms, such as fever, body aches, chills, and lymphadenopathy. Symptoms may begin with fever and malaise, and a pronounced rash appears a few days later. In recent outbreaks, lesions have formed around the genitals.
On 14 June, WHO Director-General Tedros Adhanom Ghebreyesus said who would convene an emergency committee meeting on 23 June to assess whether the monkeypox outbreak constitutes a public health emergency of international concern – the highest alert level for global health events and currently only applicable to COVID-19 and polio.
Tedros said the unprecedented geographic expansion of the monkeypox virus means that a coordinated response from the international community may be required due to the limited global supply of vaccines and medicines to prevent and treat monkeypox, and WHO is working with countries and other partners to develop mechanisms for the equitable distribution of these supplies.
On 14 June, WHO also issued new guidelines for monkeypox vaccination, but in this guideline, WHO still does not recommend the current mass vaccination of smallpox and said it is debating the use of smallpox vaccine as a way to prevent monkeypox transmission.
"While the smallpox vaccine is expected to provide some protection against monkeypox, clinical data and availability of the vaccine are limited." "Any decision on whether to use a vaccine should be made by individuals who may be at risk and their health care providers, on a case-by-case basis, assessing the risks and benefits," Tedros said. ”
In the vaccination guidelines, WHO states that "while some countries maintain strategic supplies of first-generation smallpox vaccines, it is not currently recommended to use these first-generation vaccines for monkeypox because they do not meet current safety and production standards." ”
Newer and safer second- and third-generation smallpox vaccines are also currently available, some of which may be useful for monkeypox. The third-generation smallpox vaccine, the MVA-BN vaccine, produced by Bavarian Nordic in Denmark, has been approved for monkeypox prevention. But WHO says the supply of these new vaccines is limited and access strategies are currently being discussed.
For close contacts of a patient, guidelines recommend post-exposure prophylaxis with a second- or third-generation vaccine, preferably within 4 days of first exposure, to prevent the onset of the disease. Pre-exposure precautions are taken for high-risk populations– including health care workers, laboratory personnel exposed to positive pox virus, clinical laboratory personnel who perform diagnostic tests on monkeypox, and others who may be at risk.
WHO stresses the importance of vaccination programmes, supported by comprehensive surveillance and contact tracing, complemented by information campaigns and strong "pharmacovigilance", and collaborative research on vaccine efficacy.
Dr Rosamund Lewis of WHO still says that vaccination should be done with caution, explaining that much of the data on the efficacy and safety of smallpox vaccines is old or comes from animal studies. "There's not a lot of clinical research on the latest outbreak," she said.
In its current form, can vaccines effectively control monkeypox transmission?
However, in many countries greatly affected by the monkeypox epidemic, in the face of the increasingly severe epidemic prevention and control situation, vaccination has still become an urgent response choice for the government.
According to the journal Nature, in early June, the ring vaccination campaign against monkeypox virus has been implemented in the United Kingdom, the United States, Canada and other countries. Ring vaccination is a strategy for vaccinated close contacts and high-risk populations of monkeypox relative to universal vaccination in populations.
On 14 June 2022, the European Health Emergency Preparedness and Response Agency (HERA) ordered 110,000 doses of MVA-BN smallpox/monkeypox vaccine from Bavarian Nordic in Copenhagen, Denmark, which said it would provide it to EU member states, Norway and Iceland in response to the current monkeypox outbreak. Bavaria Nordic said the delivery of vaccines to HERA would begin immediately and would be completed in the coming months, following vaccine contracts with several scattered European countries.
As early as May 25, after the first case of monkeypox appeared in the United States, the U.S. health department ordered 13 million doses of MVA-BN vaccine. In addition, the U.S. Centers for Disease Control and Prevention said the U.S. government has more than 100 million doses of the second-generation smallpox vaccine ACAM2000 in its national strategic reserve.
On June 6, the U.S. government distributed 1,200 doses of smallpox vaccine, including ACAM2000 and MVA-BN vaccines, to people at "high" or "moderate" risk of exposure. The risk of "high" or "moderate" exposure is defined as a person who has "unprotected contact" with the skin or body fluids of a monkeypox patient, or who is within 1.8 meters of an infected person.
The U.S. Centers for Disease Control and Prevention says on its website that getting smallpox and monkeypox vaccines before exposure to monkeypox can be effective in protecting people from monkeypox, and getting vaccinated after monkeypox exposure may help prevent the disease or make it less severe.
"Vaccinations are given after exposure to monkeypox virus, and the sooner an infected person is vaccinated, the better." The center recommends that "to prevent the onset of the disease, vaccination should be given within 4 days of exposure to the virus." If vaccinated within 4-14 days of exposure, symptoms of the disease may be alleviated, but it may not necessarily prevent the disease. ”
However, Natalie Dean, a biostatistician at Emory University in Atlanta, Georgia, told Nature that the current smallpox vaccination campaign is unknown and challenging, and that strategies to vaccinate close contacts of monkeypox need to rely on strict contact tracing.
Monkeypox vaccination can be a powerful tool to control the spread of outbreaks, Dean said, but to be effective, it needs to be used as early as possible — even when the number of cases remains manageable. "With the sudden emergence of numbers, the number of contacts per case is difficult to estimate, and the chain of transmission will only become more complex." She added that in countries where global outbreaks are occurring, the window period to prevent the virus from gaining a foothold in human or animal populations is becoming smaller and smaller.
According to a report by the European medical journal Eurowatch in early June, as of 24 May, only 15 of the 107 community close contacts in the UK and only 169 of the 245 health care workers had opted for the MVA-BN vaccine.
Also of concern is the protective efficacy and safety of the vaccine itself. "Although these smallpox vaccines are thought to be 85 percent protective against people infected with smallpox, this data is based on past, animal studies, with limited testing for human monkeypox." Natalie Dean said.
In early June, the U.S. Centers for Disease Control and Prevention released a research brief on ACAM2000 and MVA-BN, reporting that the second-generation smallpox vaccine, ACAM2000, is a replicable, live pox vaccine agent that is inoculated into the skin by piercing the surface of the skin. After successful vaccination, lesions will appear at the vaccination site. The virus that grows at the site of this inoculation injury can spread to other parts of the body and spread to others.
The center said it does not recommend vaccination of ACAM2000 for pregnant or lactating women, people with weakened immune systems, people with skin conditions such as eczema or atopic dermatitis, and people with heart disease. In pregnant women, this live pox vaccine virus can spread to the fetus and lead to stillbirth. In some populations, if there are people with serious immune system problems, the complications of ACAM2000 can be serious, including causing pericarditis.
The third-generation non-replicating smallpox vaccine, MVA-BN, is considered safer. Developed by Bavarian Nordic in collaboration with the U.S. government, the vaccine is a further attenuated version of the improved Ankara Pox Vaccine (MVA) virus, a highly attenuated strain of the acne virus Ankara Chorionic Allicle Vaccine Virus (CVA). In 2013, the MVA-BN vaccine was approved by the Food and Drug Administration of Canada and the United States to include monkeypox indications, becoming the only approved smallpox vaccine in the world that can be applied to monkeypox.
The main advantage of MVA-BN over ACAM2000 is that the virus cannot replicate in a vaccinated human body and there is no risk of spreading to other parts of the body or others. MVA-BN is inoculated in 2 subcutaneous injections with an interval of 28 days.
The MVA-BN vaccine is acceptable to many people with contraindications to ACAM2000 vaccination (e.g., atopic dermatitis, immunocompromised status, breastfeeding, or pregnancy), the brief said. However, because the number of immunodeficient people in the United States is increasing, these people may be less likely to produce an effective immune response, and vaccinated people may also develop infections. In these populations, the consequences of reinfection after vaccination can be particularly severe, especially after exposure to the more virulent positive pox virus.
In its report, the CDC also acknowledged that the U.S. also needs more data on the MVA-BN vaccine. For example, further research is needed to determine the duration of protection after 2 doses of MVA-BN vaccination, and the recommendations for the frequency of use of the booster can be modified accordingly; Before the immunogenicity of the vaccine reaches its peak, if positive pox virus exposure occurs, the effectiveness of a single dose of MVA-BN should be evaluated; Clinical trials are needed to assess the risk of pericarditis and serious adverse events to ensure the characterization of the risk and to provide guidance on co-administration of MVA-BN with the mRNA COVID-19 vaccine.
Epidemiologist Andrea McCollum, head of the pox virus team at the CdC in Atlanta, Georgia, also pointed out that because MVA-BN is a 2-dose injection, it is unclear whether a single dose of MVA-BN is sufficient to stop infection in the absence of trial data for human monkeypox, even within 4 days of exposure to monkeypox.
In such a situation, the control and prevention of monkeypox in the future may also need to look beyond vaccines.
Raina MacIntyre, an infectious disease epidemiologist at the University of New South Wales in Sydney, Australia, told Nature that even if more countries procure smallpox vaccines and start ring vaccination campaigns without considering vaccine availability, there are still large differences between theory and reality in implementing this strategy. Theoretically, monkeypox favors ring vaccination campaigns because it spreads more slowly than most human viruses and has a long incubation period. But in practice, the success of this approach relies on robust testing and contact tracing measures, as well as the ability to quickly vaccinate any high-risk contacts.
To stop the spread of the virus, she added, health officials may need to look beyond vaccinations and focus on isolation and community education.
WHO's Rosammond Lewis also said it was important to raise awareness of the level of risk and avoid close contact with patients. "Although the disease sometimes produces only mild symptoms, such as skin damage, it can persist in spreading for two to four weeks. In most cases, people have the option to self-isolate at home. Lewis said.
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