Highlights
In 1980, the World Health Organization (WHO) announced the complete eradication of smallpox from the planet. The elimination of the deadly virus was accomplished through worldwide smallpox vaccination. This vaccination in turn created a lasting immunity against other viruses related to the smallpox virus, reliably protecting the human population. Now that no one has been vaccinated against smallpox for a long time, a new threat has emerged in the form of monkeypox.
Monkeypox is a viral infection with clinical manifestations very similar to smallpox. In contrast to the latter, which, being highly contagious and fatal, has decimated entire cities for thousands of years, monkeypox is characterized by substantially lower infectivity and transmissibility, a lighter disease course, and a seriously reduced lethality rate.
Since routine smallpox vaccination had been abandoned worldwide by 1985, monkeypox is capable of filling the epidemiological niche left vacant by becoming a widespread infectious disease. The monkeypox virus, which has left African countries exclusively, will continue to enter human communities from both animal sources and human-to-human transmission, and the average size and duration of monkeypox epidemics across the planet will steadily increase as the level of smallpox protection declines.
- Smallpox vaccination is still available to a limited number of people: laboratory personnel working with pathogenic orthopoxviruses, some health care workers (hospital infectious disease department personnel, epidemiological surveillance personnel), some first responders, and military personnel in several countries.
Monkeypox regularly affects the forest-rich poor countries of Central and West Africa. For the rest of the world, it is a rare and neglected disease, which was only brought into the spotlight when, in May 2022, an outbreak of monkeypox struck a dozen and a half countries in Europe. This illustrates the double standard: Attention to a public health problem is only drawn to it when certain diseases strike high-income countries.
The concepts of “epidemic preparedness” and “global health” imply that any disease outbreak occurring anywhere at any given time should be dealt with immediately, without waiting for it to spill over into other countries. Health equity and fairness are crucial to global security because the problem must be addressed before it gets out of hand.
The real culprit behind the outbreak of monkeypox in Europe is the persistent and complete neglect of diseases that primarily affect the poorest populations, and the global disregard shown to the communities affected by these diseases. Effective vaccines and drugs for monkeypox should be available primarily in countries endemic to the disease, rather than being stockpiled in high-income countries on a “just to have” basis.
- What to say when on May 27, when the number of cases of monkeypox rose to 350 in Europe, the WHO stated that its priority was to try to contain the spread of the virus in non-endemic countries. Meanwhile, according to the planet’s chief medical agency, the Democratic Republic of Congo (DRC), endemic for the disease, reported 1545 cases of monkeypox and 362 deaths between early January 2020 and early May 2022.
The global attention now being paid to monkeypox, and the growing alarmist sentiment around this infection, means more investment by states and pharmaceutical companies, and that’s a good thing. That said, there should be no stigma about where the disease comes from, who gets it, or how.
There are two main scenarios concerning monkeypox and its future on a planetary scale, and they are generally favorable in the foreseeable outlook.
Scenario #1
The potential for transmission of monkeypox virus in human populations is much lower than that of smallpox. Given the wealth of global experience to date in eradicating smallpox on Earth and the extensive observations of monkeypox, it can be safely argued that it is unlikely to persist in human populations on a permanent basis even in the complete absence of smallpox vaccination. Yes, there will be periodic outbreaks, but the chains of monkeypox virus transmission will be stopped either by themselves or by simple sanitary and epidemiological measures. In other words, there should be no cause for alarm and mass smallpox vaccination is not necessary. To control monkeypox transmission, it is sufficient to adhere to symptomatic treatment, to isolate patients and their contacts, and to follow basic hygienic norms.
Scenario #2
Should the situation with monkeypox outbreaks become uncontrollable, including the aggressive spread of infection (e.g., due to virus mutations), the world’s health systems have all the resources and capabilities to produce vaccines and drugs. If necessary, ring vaccination, previously tried and tested many times in the fight against smallpox, diphtheria and Ebola, for example, will stop the spread: The strategy involves vaccinating all people who have had contact with an infected person as well as those who have had contact with them. Since the monkeypox virus is a DNA virus, it does not mutate as rapidly as RNA viruses, such as coronavirus, and therefore existing vaccines and drugs will remain effective for a very long time.
It should be understood, however, that, first, smallpox vaccines accumulated in the strategic stockpiles of states cannot be called completely safe (they can cause a number of very serious and severe adverse effects) and, second, modern medicines that are powerful and completely safe are available mainly only in the United States and Europe.
In addition to the smallpox vaccines left over from the worldwide fight against smallpox, updated and improved versions suitable for protection from monkeypox have been developed. Of particular interest is the Jynneos/Imvanex/Imvamune smallpox vaccine by Denmark’s Bavarian Nordic, which, having been approved in the United States, Europe and Canada, was the first to be officially approved for monkeypox.
The armamentarium of drugs to treat smallpox and other orthopoxvirus infections, including monkeypox, includes such drugs as intravenous Vistide (cidofovir), promoted by Gilead Sciences and Pfizer; oral and intravenous Tpoxx/Tecovirimat SIGA (tecovirimat) by Siga Technologies; Tembexa (brincidofovir), behind which is Chimerix.
Monkeypox Outbreak in 2022
O miseri! quorum gaudia crimen habent!
O wretched men, whose pleasures are a crime!
Maximianus, Elegies, I, 180.
In May 2022, a major outbreak of monkeypox began, for the first time in history, simultaneously affecting a dozen and a half countries in Europe and affecting the United States and Canada, and for the first time not associated with the spread of the disease to the population either because of the return from African regions or the importation of virus-carrying animals.
As of July 18, 2022, the number of patients with a confirmed diagnosis of monkeypox was 13,253 living in 70 countries worldwide. The top ten countries in the number of cases of monkeypox are as follows: Spain (3125), Germany (1924), United Kingdom (1856), United States (1817), France (912), Netherlands (656), Canada (539), Portugal (515), Italy (339), and Brazil (310).
It all started when the United Kingdom notified of an imported case of monkeypox in a man arriving from Nigeria on May 7. The man, who reported developing the disease with a rash on April 29, traveled from Lagos to London on May 3–4. The diagnosis was laboratory confirmed on May 6. [1]
Events then progressed rapidly, and by May 20, there were 20 infected people in the United Kingdom, all cases said to be unrelated. [2]
Around the same time, beginning May 18, reports of monkeypox began to come in from other European nations, and by May 23 the number of confirmed cases was 67 (with another 42 suspected) in nine countries, not including the UK.
All cases of monkeypox have one thing in common: Young men who self-identified as gay, bisexual, and other men who have sex with men (gbMSM) have contracted it. None of them had recently traveled to areas where the disease is endemic. Most of the cases had rash lesions of the genital and perigenital area. [3] It was later found that those infected had been to a gay fetish festival Darklands in Antwerp, [4] attended a gay party at the Berghain club in Berlin, [5] visited a gay sauna (bathhouse) in Madrid, [6] participated in a gay pride parade in Maspalomas on the island of Gran Canaria. [7]
Considering that monkeypox is not easily transmitted from human-to-human, requiring long and close contact with infected persons, a realistic picture of the spread of this infection, which has caused a large-scale outbreak, is as follows.
Western gays, being free-spirited, unassuming, and easygoing, are not averse to traveling the world in search of adventure and, of course, new sensual pleasures and sexual experiences. This permissiveness, along with the traditional promiscuity of the gay community, which manifests itself in an endless change of sexual partners, only played into the hands of the monkeypox. Indeed, more than friendly hugs and abundant exchange of bodily fluids during joyous pleasures and amusements with many strangers “no strings attached” — what other way to transmit the virus is more effective?
The UK Health Security Agency (UKHSA) has urged gay and bisexual men to closely monitor for unusual symptoms. [8] The U.S. Centers for Disease Control and Prevention (CDC) has recommended that men who regularly have close or intimate contact with other men, including men who meet partners through online websites, mobile applications, or at bars or parties, take special precautions. [9] [10] The World Health Organization (WHO) has warned of an increased risk of contracting monkeypox among gbMSM, reminding them that it can be contracted through skin-to-skin contact during sex, including kissing, touching, oral and anal sex. [11]
The Joint United Nations Programme on HIV/AIDS (UNAIDS) expressed concern that homophobic and racist attitudes are increasing due to the specific transmission and spread of monkeypox, and called on the media, organizations, governments, and people at large not to stigmatize the LGBTI community, since the infection can affect absolutely anyone regardless of sexual orientation or gender identity. [12]
Analysis of the genome sequence of the monkeypox virus that caused the outbreak in Europe confirmed that it belongs to the West African clade (genetic group), for which a lighter disease course, lower mortality (case fatality rate up to 3.6%) and limited human-to-human transmission — when compared with the Congo Basin clade (Central African clade) — are true. [13] [14] [15]
This virus is most closely related to the viruses imported from Nigeria, which were responsible for isolated cases of monkeypox in 2018–2019 in the UK, Israel, and Singapore. Relative to the latter, the genome of the current virus has undergone a number of changes (single-nucleotide polymorphisms, SNPs), and at an uncharacteristically high rate, and therefore, it is possible that it may have acquired yet unknown features. [16] It is not easy to establish the specifics of the changes quickly, given the large size of the monkeypox virus genome of 190,000 base pairs (bp); for comparison, the genomic size of the SARS-CoV-2 coronavirus is 30,000 bp.
There is an early hypothesis that monkeypox, going undetected, had been circulating in Europe long before the current outbreak, but a viral breakthrough occurred after it entered the gay community. Thus, the virus may have entered the UK a few years ago with infected travelers from Nigeria — hinted at by the identified and confirmed but counted cases of monkeypox imported into Albion between 2018 and 2021. Monkeypox is extremely rare outside of Africa and unlikely to have been known to doctors, so if it did present itself in any way, a different diagnosis was made, such as disseminated gonococcal infection. In most cases, however, the infection could be completely asymptomatic. In any scenario, the disease would go away on its own, but before it resolved, the monkeypox infected had time to transmit the virus further. So it circulated in a smoldering form fueled by hidden chains of transmission. The gay specificity of sexual behavior and lifestyle changed everything. [17]
It has been suggested that monkeypox has acquired a new mode of transmission, becoming a sexually transmitted infection (STI). But this is unlikely: the predominance of gays among the sick is the result of accidental entry of the virus into their community with characteristically high sexual activity, involving close skin-to-skin contact, through which (rather than sexual contact!) transmission occurs. [18]
- Monkeypox is not known to spread easily between humans. Close and prolonged contact is required for the transmission of viral particles through respiratory droplets. The virus can also be transmitted by direct contact with the bodily fluids of the infected person, by contact of mucous membranes or skin with exposed rashes or contaminated items such as bedding, towels, and clothing. [19] [20]
- During the September 2017 outbreak in Nigeria, cases of sexually mediated transmission of monkeypox were recorded: through bodily contact during sex or through genital secretions. [21] The possibility of infection of sexual partners is also true for the vaccinia virus. In March 2010, a woman developed vaginal lesions after unprotected intercourse with a recently vaccinated against smallpox serviceman who had removed a bandage covering the vaccination site. [22] In June 2012, a man developed a painful perianal rash after sexual intercourse with a man recently vaccinated for smallpox; the man later transmitted the infection to his other sexual partner, who developed a rash on his penis. [23]
HIV infection, which weakens the immune system, is a risk factor for a more severe course of monkeypox, with more skin lesions and associated genital ulcers. [21] HIV is more prevalent among gbMSM, of whom approximately 6% in Europe [24], than among heterosexuals, [25] but HIV-positive gbMSM are in their majority (67%–87%) [26] on highly active antiretroviral therapy (HAART), and therefore immunodeficiency in the context of monkeypox is not typical for them.
According to estimates by the European Center for Disease Prevention and Control (ECDC), the probability of spreading monkeypox is high among gbMSM and very low among the general population. The high risk for gbMSM is due, as mentioned above, to the behavioral characteristics of this community, which tends to form so-called sexual networks, groups of people who are connected to one another sexually. Interconnected sexual networks of gbMSM are characterized by having multiple sexual partners and/or multiple casual sexual contacts, attending chemsex parties (Party and Play, PNP; gatherings with taking narcotic or psychedelic substances and subsequent sex), frequent trips abroad, participation in social and public events (gay conferences, gay pride events) that do not exclude sexual contacts. All of this exacerbates the spread of monkeypox. [2]
There is another serious problem associated with the risk of transmission of monkeypox from humans to animals. An infected person can infect domestic animals, in particular rodents (mice, rats, hamsters, gerbils, guinea pigs, squirrels, etc.), which, in turn, will spread the virus further. And such transmission will become catastrophic if the virus spills over to wild animals. At present, little is known about the suitability of European or American synanthropic animal species (whose way of life is associated with humans, their homes, and the landscapes they have created or modified) to serve as hosts for the monkeypox virus. However, rodents, especially species of the squirrel family (Sciuridae), are probably suitable hosts, more so than humans. Transmission of the virus to them could lead to the spread of the virus in the wild and turn monkeypox into an endemic zoonosis. [2]
Computer simulations performed in the late 1980s to characterize human-to-human transmission of monkeypox in the complete absence of smallpox vaccine–induced immunity showed that individual monkeypox outbreaks could last up to 14 generations of human-to-human transmission before dying out. [27] [28] [29] [30]
- By “generations” is meant successive groups of cases of infection connected with successive transmission of the virus. That is, the primary case of infection belongs to the first generation; people infected by it are included in the second generation; all those infected by them constitute the third generation, etc.
Nevertheless, such outbreaks of monkeypox can recur frequently enough. According to expert estimates of 2020, in countries where natural contact with orthopoxviruses is insignificant — think of all states outside the Central and West African belt — residual immunity to orthopoxviruses has already fallen to 10%–25%, corresponding to R0 for monkeypox in the 1.10–2.40 range. In other words, monkeypox has the potential to become an endemic disease beginning with imported cases of infected humans or animals. In order to achieve reliable herd immunity against monkeypox, just over half of the exposed population (58%) would need to be vaccinated. [31]
- The basic reproductive number (R0) is a dimensionless parameter characterizing the contagiousness of an infectious disease. R0 is determined by the number of individuals who will be infected by a diseased person who gets into a completely unimmunized environment in the absence of special epidemiological measures aimed at preventing the spread of the disease. If R0 > 1, then initially the number of those infected will increase exponentially. In order to understand the comparative threat and danger of extensive spread of monkeypox, it is appropriate to give examples of R0 in common infections: chickenpox (10–12), omicron variant of COVID-19 (9.5), HIV (2–5), common cold (2–3), seasonal influenza (1.3).
On May 27, WHO held a technical briefing on the monkeypox outbreak at the annual World Health Assembly (WHA). Sylvie Briand, WHO director of the global infectious hazard preparedness, said that the world was facing an unusual situation of large numbers of cases of monkeypox appearing in many non-endemic countries over several days, which raises several questions: Whether the virus has changed, whether human behavior has changed. That said, the reported cases are just the tip of the iceberg. The obscurity and uncertainty about the virus spreading makes it impossible to assess the epidemiological risks, even though medical countermeasures exist, but their range is restricted. There is hope that the disease will prove, as in endemic countries, to be self-limiting. The general public should not panic: This is not COVID-19 or other rapidly spreading infections. Nevertheless, since smallpox has long been non-threatening, most people under the age of 45 have not received the appropriate smallpox vaccine and are therefore at risk of acquiring monkeypox, with a very limited supply of smallpox vaccines at present.
States, concerned about the growing threat of monkeypox, have begun approaching pharmaceutical manufacturers to purchase appropriate vaccines and drugs.
Thus, Denmark’s Bavarian Nordic, which has developed Jynneos/Imvanex/Imvamune smallpox vaccine, which is not only a third-generation smallpox vaccine (that is, with an improved safety profile) but also the only one officially approved to protect against monkeypox, has already received many orders to supply it. For example, Germany has asked for 40,000 doses, the UK is ready to purchase 20,000 doses, Spain is hoping for “thousands” of doses, Denmark will receive 200 doses and then another 2000–3000, and Canada already has some stock.
Siga Technologies is negotiating with European countries to supply Tpoxx/Tecovirimat SIGA (tecovirimat) for the treatment of orthopoxvirus infections, including monkeypox.
On May 27, it became known that the European Commission is going to centralize the purchase of Tpoxx/Tecovirimat SIGA and Jynneos/Imvanex/Imvamune, as the number of cases of monkeypox continues to rise and countries rush to place orders.
The U.S. has a stockpile of over 100 million doses of ACAM2000, a live replication-competent smallpox vaccine (second generation, and therefore unsafe), and continues to accumulate Jynneos/Imvanex/Imvamune, ready to vaccinate everyone who needs it.