Zhou Yebin
All current measures and efforts to target monkeypox are aimed at preventing it from becoming a chronic infectious disease in the global community – possibly similar to a sexually transmitted disease. The WHO's PHEIC discussion is also based on this context.
Monkeypox mainly affects people who are male of the same or two sexes. This group has long been marginalized and has suffered severe discrimination during the HIV epidemic. Announcing PHEIC may trigger another round of discrimination and misunderstanding among them, which is not conducive to encouraging them to cooperate with public health-related investigations.
Hands are disinfected at a monkeypox vaccination site in New York, USA, on July 30. Xinhua News Agency (Photo by Guo Ke)
Following the declaration of the monkeypox epidemic as a public health event of international concern (PHEIC) by the Director-General of the World Health Organization (WHO) on July 23, the United States also declared monkeypox a public health emergency on August 4, and the rising number of cases and the attention of international organizations and governments have made monkeypox, an infectious disease that is extremely unfamiliar to the vast majority of people, frequently reported.
On the other hand, we also need to see that Tedros's announcement of PHIC is a "breakthrough" in the absence of consensus at the international expert group meeting, which has been questioned by some people as an overreaction.
Why is monkeypox PHEIC controversial? What does PHEIC mean? What are the implications for the future spread of monkeypox?
Monkeypox in 2022 is different
Whether or not they agree with the WHO's decision to designate monkeypox as PHIC, and no matter how different the actual threat of monkeypox is, the vast majority of public health experts and scientists have to admit that this monkeypox outbreak is a little different from the past.
Monkeypox is not a new pathogen, and humans have been dealing with it for more than half a century since it was discovered in 1958. But if you compare the past monkeypox epidemics, there are still many different manifestations of this round of monkeypox transmission in 2022.
In the past, monkeypox cases have been concentrated in sporadic outbreaks in some parts of Central and West Africa. Some local rodents may be natural reservoirs for monkeypox viruses, and human contact with wildlife has led to repeated monkeypox infections in these areas.
Monkeypox belongs to the pox virus and is closely related to smallpox, which is why the current academic consensus believes that the smallpox vaccine also has a certain protective effect on monkeypox.
However, monkeypox is known to be far less contagious and pathogenic than smallpox. Until 2022, there will be little community transmission of monkeypox cases outside the African region.
In 2003, the United States had its worst previous monkeypox outbreak, with 47 cases of monkeypox infection, both confirmed and suspected, involving six states. The post-mortem investigation found that the source was that imported animals from Africa were mixed with pets sold, resulting in the infection of consumers who bought pets. From this case, it is not difficult to find that the monkeypox epidemic before 2022 is characterized by a small number of infection cases and a clear import association with Africa.
For comparison, as of August 3, 2022, the current round of monkeypox outbreaks has been reported in more than 6,600 cases of infection by the CDC of the United States, affecting 48 states across the United States. Moreover, unlike those infected with previous epidemics who have a clear history of travel and contact in Africa, according to WHO statistics, 99% of monkeypox cases outside Africa in 2022 are infected with men, of which more than 95% are gay men.
This means that this round of monkeypox has a clear phenomenon of intra-population transmission, and the way and scope of spread are significantly different from the past. This is reminiscent of the early days of the AIDS outbreak in the 1980s – the first gay male population in Europe and the United States to be affected. Although monkeypox does not make infected people carry the virus for a long time like HIV, nor is it as deadly as HIV, public health experts have to worry about whether monkeypox will camp in human society and become another long-standing infectious disease.
Thus, the threat of transition from an occasional sporadic tropical disease to a long-standing infectious disease among populations may explain why the WHO, as well as the public health authorities of Europe and the United States, attach great importance to monkeypox.
All current measures and efforts against monkeypox are aimed at preventing it from becoming a chronic infectious disease in the global community – perhaps resembling a sexually transmitted disease. The WHO's PHEIC discussion is also based on this background.
What does it mean for monkeypox to become PHEIC?
After the WHO declared monkeypox a PHIC, some readers may feel that the monkeypox epidemic has become serious, but the more question worth investigating is: What does it mean to become a PHEAC?
Public health events of international concern, PHEIC, fall under the WHO's category of declarations that "constitute a public health risk to other countries through the international spread of the disease and may require a coordinated international response".
PHEIC actually represents a series of WHO assessments, testing, and coordinated responses to international public health threats.
As we all know, promoting the prevention and control of global epidemics is one of the main functions of the WHO, but in the context of a highly unbalanced global development, it is not easy for the WHO to improve the global public health prevention and control capacity. Especially when it comes to assessing and responding to a public health problem with potential international threats, the WHO often faces two diametrically opposed criticisms of "making a fuss" and "acting slowly" at the same time.
PHEIC's statement mechanism was established in 2005, and one of the backgrounds was the SARS epidemic in 2002-2003, that is, when a new type of virus spreads, public health problems can quickly break through national borders, from a country's problem to an international crisis, and a timely response requires more reasonable international risk assessment and coordination.
What PHEIC wants to solve is the delay in the discovery and confirmation of major public health risks by the international community. One of the reasons for these delays is that in the places where the public health problem first appeared, it will be accompanied by the problem of local data collection and judgment of severity is not timely enough.
Taking monkeypox as an example, the natural occurrence of this disease is in Central Africa and West Africa, which is an area with relatively poor sanitary conditions, and it is likely to exceed the actual local capacity to track the dynamic changes of an infectious disease in time.
In this regard, PHEIC provides a mechanism for regional declarations to the WHO, which is conducive to the rapid transmission of potential public health crises to the WHO, who will do further assessment. The nomination includes not only WHO member states, but also NGOs, which reduces the risk of missing sources. More critically, the PHEIC declaration also provides a criterion for judging what kind of situation should be declared according to the PHEIC.
Four criteria:
Are the impacts on public health severe?
Was the event unusual or unexpected?
Are there significant risks associated with international dissemination?
Are there significant risks associated with international travel or trade restrictions?
In accordance with the regulations, if either of the above articles is met, Member States should declare potential PHICs to the WHO. In addition to infectious diseases, nuclear leakage and chemical pollution can be declared, but the PHEIC declarations announced so far belong to the field of infectious diseases.
Still taking monkeypox as an example, the speed and scope of transmission of this round of epidemic in 2022 are significantly different from the past, and the risk of international spread is serious, causing a threat to public health, which is clearly in line with PHEIC standards. In addition, in order to further reduce the risk of under-reporting, the declaration of potential PHEICs also lists a list of diseases that can be declared immediately after discovery, including SARS, smallpox, polio, and new influenza viruses.
Once the WHO receives a potential PHIC report, it will hold a discussion to confirm whether a PHIC needs to be announced. This step is actually another kind of delay in resolving the international public health crisis – when there is an epidemic in one place, the entire international community often has a delay in understanding the potential risks.
Under the PHIC mechanism, WHO's Emergency Committee can conduct a comprehensive analysis of specific potential reporting data to assess compliance with PHEIC's criteria. Finally, the DIRECTOR GENERAL OF THE WHO decides whether to declare PHIC based on the opinion of the Committee, as well as other evidence.
It is not difficult to see from the declaration and declaration process of PHIC that the WHO hopes to accelerate the judgment of the public health crisis by the international community with more scientific and unified standards. The reason is that for any public health crisis, intervention at an earlier time is more likely to be successful and less costly.
Since its establishment in 2005, there have been six PHEIC statements, including monkeypox: swine flu in 2009, polio in 2014 (still unrestrained), Eboa virus in 2014, Zika virus in 2016, Ebola virus in 2018 and COVID-19 in 2020 (still not lifted).
But after the PHIC statement, a more realistic problem emerged - although the WHO has recommended countermeasures, there are actually no coercive measures and no fixed resource allocation.
The above dilemma has become the focus of questions about the practical significance and role of PHIC. It is also important to note that PHEIC highlights the threat of international proliferation, which is corresponding to recommendations that are often accompanied by international travel restrictions. This is a disguised punishment for many outbreak areas – once PHIC is declared, the place of occurrence is likely to be hit economically by travel trade restrictions. On the contrary, the WHO recommended countermeasures, such as international resource allocation, are not mandatory, and it is difficult to ensure that the outbreak occurs to receive actual support.
Support and opposition to monkeypox PHIC
The controversy over the meaning of PHEIC also extends to this monkeypox. The difference is that the previous five PHIC statements have been implemented on the unanimous recommendation of the Emergency Committee, while Monkeypox failed to agree on the PHIC recommendation in two WHO emergency meetings in June and July this year.
Among them, the June meeting was not recommended pheeic statement, and in the July meeting, there was an outcome supported by 6 experts and opposed by 9. Although the Director General of the WHO has the final jurisdiction of PHEIC, this approach, which is different from past practice, is naturally more interesting.
Whether for or against declaring monkeypox as PHEICs, some basic facts are not in dispute. It is precisely one part of the facts that support PHEIC, while other basic facts are the reasons for opposing PHEIC.
First, monkeypox cases are indeed growing. According to data cited in the two WHO monkeypox emergency meetings, the epidemic affected 47 countries in June, and by July 20, the number rose to 72 countries. As of 20 July, global monkeypox cases rose to 14,533, surpassing 26,000 by 4 August. These figures are fully in line with PHEIC's criteria of having a significant risk of international spread and a serious impact on public health.
Second, infections remain concentrated in gay men – 99% of cases are in gay men. A small number of cases of women and children can almost always be traced back to close contact with gay men. As we mentioned earlier, the characteristics of such infected people are very different from previous monkeypox, and they also meet the criteria for epidemic abnormalities in PHIC.
But other basic facts make it debatable whether monkeypox needs to be classified as PHEACs. For example, the vast majority of cases are concentrated in male same- or bisexual people with multiple sexual partners, meaning that monkeypox has not spread to other populations. Even from the modeling of european countries most affected by monkeypox, only in male homosexual populations monkeypox R0 (the basic number of infections) is higher than 1, in other populations it is less than 1, and even in male homosexual population R0 is less than 2.
This means that the actual transmission capacity of monkeypox is still relatively weak, and PHEIC must consider not only the spread of an infectious disease in the past period of time, but also the threat in the future. Judging by the spread of monkeypox and the limitations of the population, it seems difficult to say that its threat will increase significantly.
In addition, the pathogenicity of monkeypox was not enhanced. When the WHO declared monkeypox PHIC, there were only 5 deaths worldwide, all in Africa. As of 4 August, the number of deaths has risen to 10, including 6 in Africa, 2 in Spain, and 1 each in Brazil and India. Deaths outside naturally occurring regions are certainly worthy of attention, but the monkeypox mortality rate of more than 25,000 infections worldwide remains low.
In summary, the abnormal manifestations of monkeypox seen now are more that the mode of infection seems to be different from the past, and the concentrated transmission of male homosexual populations cannot rule out the changing trend of sexually transmitted diseases, but the pathogenicity remains at a low level and makes the urgency and importance of declaring monkeypox as PHIC questionable.
Another reason that makes the need for PHEIC even more confusing is that many people have to ask: What kind of help can announcing monkeypox PHEIC really help?
Most people will agree that once the PHEIC is announced, it can increase the global attention to a public health incident, that is, the declaration of PHEIC can increase the public's attention to monkeypox, thus playing a complementary role in tracking the infected and close people.
However, opponents of the monkeypox PHIC decision will point out that monkeypox is already in the global concern, and declaring PHEICs will not further increase attention. In addition, monkeypox mainly affects the same-sex or bisexual population of men. This group has long been marginalized and has suffered severe discrimination during the HIV epidemic. Announcing PHIC may trigger another round of discrimination and misunderstanding among them, which is not conducive to encouraging them to cooperate with public health-related investigations.
It is from different perspectives that the opposite conclusion can be drawn, the WHO's monkeypox emergency meeting failed to make a unanimous recommendation for PHIC, and even the number of opposing votes of the participating experts exceeded the number of votes in favor. However, the WHO Director-General Tedros Adhanom Ghebreyesus, who has the right to decide, still believes that it is more advantageous to make a PHIC statement for monkeypox after further weighing.
One of the possible speculations that influenced this decision was that the WHO, while declaring monkeypox as PHIC, also proposed a differentiated prevention strategy for the differences in the epidemic situation between countries. It can be said that PHEIC is an opportunity for the WHO to recommend its own epidemic prevention suggestions to countries and seek global coordination and cooperation.
Can PHEIC change the development of monkeypox?
The immediate question is, can the opportunity for epidemic prevention advice brought by PHEIC really work?
Specifically, the WHO has put forward recommendations for epidemic prevention in countries under monkeypox PHEIC:
The first is countries that currently have no cases (such as China) that need to strengthen surveillance to help prevent the further spread of the epidemic;
The second category is countries with the spread of the epidemic and need to prevent the spread from intensifying. In addition to isolating infected people and contacting close contacts, there is also a need for targeted use of smallpox vaccines that are also effective for monkeypox – for example, as a therapeutic treatment for infected people, and preventively for close contacts and healthcare workers;
The third category is the countries and regions where there are cases of monkeypox transmission between animals and humans (such as some countries in Africa), and it is also necessary to pay attention to the transmission between animals and humans, whether there is a human-to-animal transmission.
In addition to the above three categories, there is also a category of countries that have the ability to develop and produce related medical materials, such as countries with smallpox vaccine production capacity. The WHO's recommendation is that these countries should coordinate the global supply of pharmaceutical resources.
The statements and recommendations are very clear, but whether these WHO efforts can have a positive impact on the development of the monkeypox epidemic will depend on the actual implementation of countries, especially in the allocation of cooperative and coordinated resource allocation.
It can be seen that for those countries that have resources for vaccines and tests, long before the WHO recommendation or PHIC statement, they have been strengthening surveillance and taking measures to reduce the spread of monkeypox.
But the problem today is that whether it's vaccines, therapeutics or tests, the number available worldwide is limited. Taking vaccines as an example, from the perspective of safety, only non-replicating third-generation smallpox vaccines are suitable for monkeypox, which is currently in limited global stocks, most of which are supplied to European and American countries, but are still in short supply.
In this case, how to make the resources of drugs and treatment more suitable for the actual epidemic situation, rather than the economic development of various countries, will be a challenge that THE WHO has to face.
In theory, the announcement of PHEIC could prompt organizations such as the World Bank to support under-resourced countries hit by the pandemic. However, the resource gap of the monkeypox epidemic lies in the lack of related drugs, tests and other physical objects, and it remains to be seen whether only more economic assistance opportunities can be converted into medical resources.
In addition, monkeypox research remains scientifically uncertain. A growing body of evidence points to a sexually transmitted disease, such as the concentration of infected populations in male same- or bisexual populations with multiple sexual partners, such as some studies showing the presence of viral DNA in semen, which can lead to large differences in patterns and scopes from past monkeypox transmission.
However, regardless of whether monkeypox can be transmitted sexually, the transmission of the virus to humans still relies heavily on prolonged close contact.
If the public can have more awareness of the virus, especially in high-risk populations through knowledge education to increase vigilance, coupled with epidemiological investigations such as case tracing, then it is still promising to control the further spread of monkeypox and prevent it from becoming a new sexually transmitted disease that has existed in the world for a long time.
But this requires the WHO's PHIC to raise public awareness while not intensifying prejudice and discrimination against men of same-sex or bisexual orientation. This may be the variable that has the greatest impact on the trend of the monkeypox epidemic.
(The author, Zhou Yebin, Ph.D. in genetics, has been engaged in immunology research for a long time and is currently engaged in new drug research and development in pharmaceutical companies.) This article is edited by Liu Chu. ）
Bibliography:
1. https://www.nytimes.com/2022/08/04/health/monkeypox-emergency-us.html
2.https://www.who.int/europe/news/item/23-07-2022-who-director-general-declares-the-ongoing-monkeypox-outbreak-a-public-health-event-of-international-concern
3. https://www.who.int/news-room/fact-sheets/detail/monkeypox
4.https://wwwnc.cdc.gov/travel/yellowbook/2020/travel-related-infectious-diseases/smallpox-and-other-orthopoxvirus-associated-infections
5.https://www.who.int/news/item/23-07-2022-second-meeting-of-the-international-health-regulations-(2005)-(ihr)-emergency-committee-regarding-the-multi-country-outbreak-of-monkeypox
6.https://www.cdc.gov/poxvirus/monkeypox/vaccines.html
7.https://www.nejm.org/doi/full/10.1056/NEJMoa2207323
Responsible editor: Zhang Jing Photo editor: Jiang Lidong
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