With the advent of vaccines, will the new coronavirus be eradicated?

Why do many infectious diseases have corresponding vaccines but have never been eradicated? Will the new coronavirus be like them?

Text｜Xu Ziming

Although most of the new coronavirus vaccines have not yet been officially launched on the market, all of humanity has high hopes for these "magic bullets" and regards them as weapons to completely defeat the new coronavirus.

There is a popular view that as long as the vaccine is available, the new coronavirus will be defeated and quickly eliminated by humans. At the same time, there are often such questions on the Internet: Isn’t the vaccine already available? Why is the epidemic not under control?

But in fact, in history, there are only two infectious diseases that humans have confirmed to have been completely eradicated: smallpox and rinderpest. Even those infectious diseases that the public thought had long been "swept into the dustbin of history", such as polio, tuberculosis, measles, diphtheria, Japanese encephalitis, rubella, whooping cough, etc., are still active in some corners of the earth, and most of them have vaccines.

In this way, it is the norm that infectious diseases cannot be eliminated even with vaccines, and it is the exception that vaccines are invincible. This is not because vaccines are ineffective, but because of cost and conditional restrictions, unfair distribution, and the complex social ecology of human beings.

Will the new coronavirus vaccine fall into this trap?

Is it a sure loss? Doing some calculations for vaccines

Most low- and middle-income countries do not have a spontaneous vaccine market. The "drug regulatory authorities" in many countries lack the ability to approve vaccine products, or even do not have such a department at all. These areas also often lack cold chain transportation and storage conditions, lack of manpower to handle and vaccinate vaccines, and lack of public recognition of vaccination.

From this perspective, vaccination in low- and middle-income countries seems to be a "guaranteed loss-making" business.

Is this really the case? How valuable, or not valuable, are vaccines? How much more money would it cost to add a universal vaccine?

Let's take Ebola as an example to do the math: Ebola vaccines require ultra-low temperature cold chain transportation at minus 60 to 80 degrees Celsius, making it one of the most expensive vaccines.

According to an estimate by the WHO in 2016, 31,094 doses of Ebola virus vaccine were distributed in one region in Africa. The cost of the vaccine itself was about US$830,000, the cost of human and material resources for vaccination was about US$430,000, the cost of cold chain transportation was about US$1 million (once laid), and the cost of renting a site and organizing the vaccination was about US$630,000 - a total of about US$3.38 million. Excluding research and development costs, the average cost per dose is US$135.9.

On April 5, 2017, the second phase of the Ebola vaccine clinical trial, volunteers received vaccination

At this cost, giving each of the 367 million people in West Africa one dose would cost nearly $50 billion. But in reality, the cost of controlling Ebola with vaccines is far less than this figure. In each country, vaccines can first be provided with millions of dollars of funds, with priority given to medical staff and the areas with the most serious epidemics, and then whether to promote them will be decided based on the situation.

Currently, fewer than 400,000 people have been vaccinated against Ebola, and a reserve of another 500,000 doses is under construction.

Traditional cost-benefit decision-making mechanisms usually only consider commercial interests. Obviously, no low-income country can independently support a market that is sufficient to make a profit. Therefore, in the first thirty years after the discovery of the Ebola virus, this field was considered unpopular in the world, with almost no projects and no funding.

It was not until the Ebola outbreak in West Africa in 2014 that the international community changed its thinking and realized that the main returns from the Ebola vaccine did not come from the market.

The World Bank estimates that from 2014 to 2015, the total economic losses of West African countries due to the epidemic could reach US$3.8-32.6 billion.

In West Africa, the social cost of a fully recovered Ebola patient is between $480 and $912. The social cost of a non-survivor is between $5,929 and $18,929, which is several to dozens of times the annual per capita GDP. If vaccination had not been introduced since 2016, and the disease spread to more economically developed countries, the loss of each case would have been even greater.

Compared with the global "black swan event" that could reach trillions of dollars, the billions of dollars that the international community has invested in Ebola vaccines are worth every penny. Even with such an expensive vaccine, the world has not lost money.

If health is viewed as a commodity, then the people in the world who have the least access to medical care and medicine and who live in an environment where disease is rampant are precisely the most price-sensitive consumers - the poor.

In many cases, even a symbolic fee for health services may significantly reduce the number of poor people receiving medical treatment. Many people would rather die at home due to untimely treatment, or rely on "gods" to make their own medicine at home, rather than use more reliable but expensive health care methods.

In Papua New Guinea, once maternal and child clinics began charging, the rate of first visits by pregnant women dropped by 30%. In a province in Burkina Faso, when some hospitals began charging, the frequency of visits to these hospitals decreased by 15.4%, while the frequency of visits to free hospitals increased by 30.5%. In rural Kenya, when hospitals began charging, a large number of people went to pharmacies instead.

· From charging to canceling registration fees, the change in the number of people going to hospitals (white) and pharmacies (black) was immediate

This phenomenon rarely occurs in developed countries or among non-poor people.

Therefore, in the field of health, it is still important to ensure basic distributive fairness through external forces such as multilateral mechanisms and international aid. Although these methods are often criticized for unclear goals, low efficiency, and opaque funding, without them, basic health services would not exist in many parts of the world. Regional epidemics may spread rapidly around the world because they are out of control, and underdeveloped regions may be dragged down by some preventable and treatable diseases for a long time and be unable to obtain development opportunities.

Faced with Ebola, humans almost made a very wrong decision. Fortunately, with the financial stimulus of international organizations, several Ebola vaccines were quickly developed and vaccinated in the areas most affected by the epidemic, thus curbing this crisis that could have caused future troubles.

Some other diseases are not so lucky.

Fair distribution, lessons from H1N1

During the pandemic, vaccines have not been fairly distributed between rich and poor countries due to production and procurement monopolies, leading to serious epidemic prevention and diplomatic consequences.

Just ten years ago, the situation of the H1N1 influenza epidemic and vaccine was very similar to the current COVID-19.

This new influenza A (H1N1) virus first swept the world in 2009. In the early stages of the outbreak, it appeared to be highly contagious and its sequence was different from the seasonal influenza A (H1N1) virus and very close to the virus that caused the 1918 Spanish flu pandemic.

Vaccines are the only option for dealing with this fast-spreading virus. But because of this, countries around the world are arguing over it.

As we all know, the immune protection period of influenza vaccines is not long, generally only one year, and influenza A vaccines are no exception. In February every year, WHO will hold an expert meeting to infer which influenza strains are likely to come in the autumn and winter of the northern hemisphere based on the monitoring of the previous year, and give the strains to vaccine manufacturers.

Every year, influenza vaccines use relatively mature basic technology, but only need to replace the strain, and generally do not need to undergo complete clinical trials. Therefore, the development of influenza A vaccines is easier than other vaccines. By the fall of 2009, influenza A vaccines had been launched in countries around the world.

At that time, the world had not seen a pandemic in decades, and both international law and trade lacked a solution framework to ensure fair access to vaccines under emergency conditions. Developed countries quickly snapped up almost all of the world's influenza A vaccine production capacity.

The WHO and the United Nations successfully pushed developed countries and manufacturers to donate some vaccines to developing countries, but many promises were delayed or not fulfilled due to the lack of production capacity in advance. The United States promised in September of that year to donate 10% of the vaccines it purchased to the WHO, but a month later, it had to go back on its word because of a shortage of production capacity. Canada and Australia also chose to prioritize domestic demand before exporting for the same reason.

From left to right in the figure are the vaccine utilization rate by region, the WHO vaccine deployment plan, and the actual vaccine coverage rate.

The distribution of influenza A vaccines in countries around the world is extremely uneven. Most countries that did not get the vaccine first eventually had a vaccination coverage rate of less than 10%, which in turn affected the direction of the epidemic itself.

Africa and Southeast Asia account for only 38% of the world's population, but 51% of deaths from influenza A. Africa reported few cases of influenza A due to limited testing conditions, but according to model estimates, 29% of respiratory deaths caused by influenza A occurred in African countries, and the estimated mortality rate is about 2 to 4 times that of other countries.

By 2010, WHO and various international organizations had managed to raise a total of more than 70 million doses of influenza A vaccine and opened applications to low- and middle-income countries around the world. Until August 2010, WHO announced the end of the global influenza A pandemic, but these countries - mainly African countries - still needed a large wave of vaccines (the highest point of the black line in the figure below) because the influenza A had not left them.

In 2010, the batches (blue) and quantities (black line) of influenza A vaccines sent by WHO each month

Until the end of the epidemic, the diplomatic issue involving the H1N1 flu vaccine remained a mess. Many developing countries angrily accused developed countries and manufacturers of being dishonest and hoarding; some people in the European Union accused large manufacturers of pushing the WHO to exaggerate the dangers of the H1N1 flu in order to sell vaccines, when the virus was actually not that fierce.

In any case, after this unsuccessful exercise, facing the more difficult new coronavirus, the international community at least quickly established mechanisms such as the COVID-19 Vaccines Global Access (COVAX) program.

Simply put, what COVAX wants to do is what was not fully achieved ten years ago: raise funds from all parties around the world through multilateral mechanisms, and use this money to do two things. One is to provide impetus for vaccine research and development by pre-purchasing certain vaccines before they are available; the other is to provide vaccines to countries joining the organization according to a certain population ratio and provide assistance to poor countries to ensure fair distribution of vaccines among different countries.

It is not possible to predict whether these mechanisms will succeed, but escaping from a mess is often the first step to success.

Why must it be "eliminated to zero"?

Experts in global health and public health often give people the impression of being nitpicking: Why do we have to eliminate infectious diseases to zero? Even if there are only a few dozen or even a dozen cases left in the world, living in a corner of the earth, why can't we just control infectious diseases like COVID-19 to local epidemics, but must eradicate them?

· Malaria deaths per 10,000 people in each continent since 1900. Humans launched a large-scale elimination campaign after World War II, but failed to completely eradicate malaria due to changes in the political and economic environment. Since the 1970s, malaria in many African countries has rebounded from near elimination to previous levels, and has continued to export cases to other regions (the black dot curve represents African countries)

International organizations and charities always like to say: "As long as there is a place in the world where XX disease exists, human beings cannot be free from danger." It sounds like it goes against the principles of economics, but there are many lessons to be learned from not doing so, which leads to serious consequences.

Poliomyelitis (poliomyelitis, abbreviated as polio) is an infectious disease that humans have been relatively successful in dealing with. Due to the effectiveness of the vaccine, the number of cases worldwide has continued to decline rapidly since the 1980s until the beginning of the 21st century.

But the "second half" of polio eradication seems to be even more difficult. It took humanity 20 years to reduce the number of new cases from 400,000 to 2,000 per year. It also took humanity 20 years to reduce the number of new cases from 2,000 to the foreseeable zero, and it may take even longer - because zero has not yet arrived.

The number of polio cases worldwide each year, with different colors representing different regions

The reason why the "second half" is relatively long is not because health workers have stopped working hard. In fact, the delicate balance between us and the remaining "stragglers" of polio is still achieved through massive vaccination, emergency treatment, and active treatment.

After 2015, there were only a few "strongholds" of polio left in the world, one of which was Nigeria.

In 2003, the Kick Polio Out of Africa campaign was at its peak. Just as countries were working hard to build a cold chain for vaccines by hand and shoulder, a serious wave of vaccine boycotts broke out in northern Nigeria.

People in northern Nigeria have little habit of accessing modern medical services. In 1990, 50% of residents in southern Nigeria used formal health services, while only 18% in the north did so. This ratio increased to 64% to 8% in 2003.

After the 9/11 incident and the Iraq War, local people became increasingly distrustful of things from the West for religious reasons. Some local civil leaders spread rumors that vaccines from the West would cause infertility, AIDS, and cancer (Note: attenuated vaccines do have a very low risk of causing recipients to contract polio, but the rumors did not mention this).

The rumor quickly triggered a boycott and spread to the local government with weak administrative capacity. In Nigeria, the federal government is responsible for tertiary/comprehensive health care facilities, while state and provincial governments are responsible for primary and secondary health services. Since immunization belongs to primary health services, the state and provincial governments have jurisdiction, and Kano provincial government officials directly stopped Nigeria's national polio immunization program.

As a result, in October of that year, a new wave of polio virus spread from northern Nigeria to the entire country and many African countries. By 2006, the five provinces in northern Nigeria accounted for more than half of the world's polio cases, and more than 1,500 children were paralyzed. It was not until 2020 that wild polio was completely eliminated in Nigeria and the African continent.

Distribution of polio cases in Nigeria and surrounding areas in 2002 (left) and 2003 (right)

Currently, Pakistan and Afghanistan are the only two countries in the world that have not yet eradicated wild polio. Both countries have been trapped in war for a long time. Since 2012, more than 90 polio vaccine workers have been attacked and killed in Pakistan.

In 2019, a polio vaccine panic occurred in Pakistan due to a staged rumor video, which led to attacks and killed several people. Even so, the international community did not give up. At the call of the United Nations and international organizations, the warring parties in Afghanistan ceased fire several times, and medical staff were able to enter the Taliban-controlled areas to vaccinate

Both countries are China's neighbors. The last case of wild polio infection in China was eradicated in 1994, but in 2011, imported polio broke out again in Xinjiang. This wave of epidemic was likely from Pakistan. After more than 43 million emergency immunizations, the WHO once again announced that China had eradicated polio in April 2012.

To prevent importation, China still retains this vaccine in its immunization program after more than 20 years without wild polio. Helping neighboring countries advance polio eradication can help millions of Chinese newborns get fewer shots and parents have fewer headaches.

The world is indeed connected -- connected by bacteria, viruses and parasites. The infectious diseases that remain in some corners may be more relevant to us than we think.

It is for this reason that it should become a consensus to fairly distribute the new coronavirus vaccines that are being launched in waves, make long-term plans in terms of cost-benefit, and leave no blind spots in any region.

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