Fighting history’s most successful infectious disease

In the years since the 1990s tuberculosis has once again become rampant across the globe. This is due to several factors, including greater mobility and the neglect of TB prevention and treatment. In the twenty-first century, worldwide TB prevention and treatment remain problematic. The world faces challenges: the increased number of multi-drug-resistant patients, TB and AIDS co-infection, and inadequate funding for prevention and treatment.

Huan Shitong, senior project officer focusing on TB in the Gates Foundation’s Beijing office, was invited to give a keynote speech titled ‘The Most Successful Infectious Disease in the History’ at Yixi (the TED talk platform of China). This article is an edited version of Huan’s speech.

If an infectious disease had intellect and could think like a human, it would probably strive to become the “alpha” among its peers. Its war cry would be “take no prisoners.” In other words, it would be the type of assassin that disappears without a trace after killing their victims. What disease fits this description best? I’d have to pick tuberculosis.

What makes this killer so cold-blooded? It arrives suddenly and leaves without a trace.

Let’s look at a few figures. The first figure is 1.7 million people. That’s the number of deaths caused by tuberculosis every year. What exactly does 1.7 million mean? It means that tuberculosis is the deadliest of all communicable diseases. Even if you count all the deaths from cardiovascular disease, cerebrovascular disease, lung cancer and liver cancer together, tuberculosis is still easily within the top ten deadliest diseases.

The second figure is 10,000,000. That’s the number of new cases of tuberculosis diagnosed every year. How about throwing in another number—and this one is a big one—two billion. The planet is home to seven billion people, and two billion of those are infected with tuberculosis bacteria, which in medical terms is known as latent infection.

So, what about the figures for China? Different pieces of research have produced different estimates. What is fairly certain is that the number of people with a latent tuberculosis infection lies between 200 million and 550 million, which means that the bacteria are present in at least 200 million people in China.

Humans have lived alongside tuberculosis for about 5,000 years. However, it has only been a focus for mankind for the past two centuries. Why did people only start paying attention to tuberculosis 200 years ago? Perhaps because at the time, numerous big names in the world of literature and the arts—Shelley, Princess Sissi, Lu Xun, Byron—began contracting a peculiar ‘consumptive’ illness. That illness was tuberculosis.

TB wasn't only rife among history’s equivalent of our internet celebrities. It cast a long shadow across the whole of society.

Robert Koch (1843-1910) discovered the agent that causes tuberculosis. He said that tuberculosis was a greater threat to humans than even the most terrifying of communicable diseases like the black plague or cholera. This was because according to his statistics, one in seven people at that time in Europe could be expected to contract and die from the disease.

At the end of the nineteenth century, following the industrial revolution, and as economic growth and civilization reached unprecedented eights in Europe, countries across the continent began to compile statistics on tuberculosis. Like most of the rest of the world, China does not have any quantitative data for the same period, rather it only has some qualitative indicators.

For example, there is a passage in the film Fist of Fury where the characters in the film smash a sign bearing the words, “Sick man of East Asia.” Many people interpret this as a reference to one of the commonly found infectious diseases in China at the time: tuberculosis.

How has mankind confronted this cold-blooded killer for the past 5,000 years?

In the past, people thought that if there was something wrong with the lungs, then the solution was to go and breath clean air. Being sent off to a place with a nice view to get some sunshine was thought to be the best cure.

That is how Davos in Switzerland became famous—as destination for tuberculosis sufferers to get treatment. The picture below shows one of the clinics there. Each room has beds outside for patients to lie in the sun. Of the cures available at the time, it was probably not so bad.

This type of cure, however, called for a certain degree of wealth: it was a rich person’s remedy. So, what happened to poor people who contracted the disease? Based on religious reasoning, people believed that if you fell ill, it was because you had sinned, and disease was a punishment which required help from God.

From the fifth century AD a practice appeared in Western Europe whereby monarchs designated a certain day in the year to bless the sick through a laying on of hands. Even though this ritual had no effect whatsoever, it persisted from the fifth century through to the fifteenth century? The question is, why? This is related to one of the characteristics of TB.

A third of those falling ill with TB would die within two years. A second third could live for a further five to ten years, during which time their bodies would become weak—as if ‘consumed’ from within—making the illness chronic, whilst they continued to spread the bacteria to those around them. The last third, perhaps because the initial infection was only superficial, or their immune system was stronger, would eventually recover naturally.

This meant that one third of those blessed by the monarch eventually recovered, generating the belief that monarchs had been given curative powers by God.

What can we do to fight this illness today? Vaccination! And…

The first weapon against the disease is prevention. We all know that every child born in China today is given two injections: one against viral hepatitis B, and one known as the BCG jab. The BCG protects children against tuberculosis, and inoculation at birth increases their resistance to tubercular meningitis or tuberculosis elsewhere in the body.

Nevertheless, the BCG only boosts the immune system. It doesn’t offer children definitive protection against TB. Beyond vaccination, considerable progress was made in the field of antibiotics between the 1940s and 60s, with some new products found to be effective in combating TB. Doctors were finally able to cure 90 percent of patients with the disease, as well as reducing the period of treatment from one year to six months. At last, everyone believed that this would lead to the elimination of tuberculosis for good.

Looking around us today, however, it’s clear that the disease has not been stamped out. This, again, is due to three characteristics particular to TB.

The first can be put simply as ‘airborne-ness’, i.e. its airborne transmission. Someone infected with the disease can through a sneeze or cough project the bacillus into the air and infect the people around them.

The second feature of the disease is ‘latency’. When the TB germ enters a host, if it detects a healthy body with a robust immune system, it will automatically enter sleep mode without causing any harm.

As such the immune system does not consider it to be a harmful organism and leaves it to survive in the body. If the body’s immune function weakens at any time, the bacillus will pick up the associated signals, awaken, and begin to multiply, causing the host to start coughing, expelling it into the air in search of a new host.

The third characteristic is ‘iteration’. Today numerous drugs have been developed to fight TB. However, to kill the germ, three or four drugs at least are required for a treatment lasting six months. So, what happens if you use only one medicine?

Well, in the space of one month, the bacillus will have developed a resistance to the drug, and the next generation of germ will therefore be resistant to that treatment. Because of this capacity to iterate, a new form of TB has emerged called drug-resistant TB (DRTB).

The number of people who have DRTB is around 500,000, with 70,000 of those cases in China alone. Since DRTB can be spread by airborne transmission, if left untreated an individual carrying DRTB may infect up to fifteen others over the space of a year.

It is not possible to eliminate DRTB with just one drug. Even if three to four new drugs were discovered, it would still take six months of treatment to be in the clear.

Patients with DRTB therefore need to follow a treatment that lasts two years, which will set them back between 80,000 to 100,000 RMB, and which has a success rate of only 50%. To make matters worse, there is one strain of the disease which has exceptionally high drug resistance and cannot be cured even with a broad cocktail of drugs. It is not an exaggeration to say that if this type of DRTB is not kept under control, it could become a kind of communicable cancer, to which everyone would be vulnerable.

What can we do? Tremble with fear?

Controlling communicable disease always relies on a two-pronged approach. The first line of attack is vaccination. For example, the scourge of viral hepatitis B mentioned earlier has now been checked, and children are today well protected through inoculation.

However, there is a problem with developing a TB vaccine. With other diseases such as smallpox, after inoculation the body produces antibodies offering lifelong protection. TB is not the same. Even after recovering from TB, a person can become re-infected and fall ill again.

The Bill & Melinda Gates Foundation invests hugely in vaccines, earmarking about $100 million of their budget every year for TB tools development. About half that amount is for developing the vaccines. We continue to pursue this first approach.

But we also need the second approach, which is a longer, more difficult route: to identify as many infected people as possible and cure them. This approach also requires the development of a whole battery of new tools and medicines. Today we have molecular diagnostics to detect new cases of TB quickly, and to tell within about two hours if the TB is drug-resistant. This shortens the diagnosis and treatment time dramatically. As part of this initiative, we calculated that the time it takes from receiving a sample from a patient to telling them it is DRTB and commencing treatment, is only 7 days.

However, just as important as having a tool is using it.

What has the Gates Foundation done in China in terms of TB prevention?

The foundation has been cooperating with China’s National Health and Family Planning Commission for nine years, focusing on improving the health system in three key ways.

Firstly, by increasing the efficiency of the health system. This is done by encouraging closer cooperation between hospitals, disease prevention centers and grassroots operations. This is especially important with district hospitals and health centers in townships and villages where they need help detecting cases of TB more quickly so that they can start treatment and manage their patients.

Secondly, by ensuring that new diagnostic is applied and used in the field to detect infected people more quickly and introduce new treatments. We also use patient management tools such as electronic medicine boxes, which enable us to monitor how patients are taking their medicine in a given period.

Thirdly, by resolving financial problems. The fund works alongside medical insurers, government spending departments and civil administration to discuss how best to resolve the problem of patient treatment, because an ordinary household is unable to simply come up with 80,000 to 100,000 RMB to pay for treatment.

About a third of mankind today, which is about 2 billion people, is carrying the dormant—but still live—bacillus. There is no need for panic, however, since only 5 percent of those people will become ill with TB. The remaining 95 percent just need to keep an eye on their health, stay fit, and rest properly to steer clear of the disease.

But aside from all this, there are still some aspects of the disease that we don’t understand: How exactly is it transmitted? What is the relationship between the concentration in the air and actual infection and appearance of the disease? How long exactly is the incubation period? How can dormant bacilli found in a patient be killed? How is it possible to know if someone is completely recovered from TB.

More research and investment are needed to answer all these questions. Maintaining effective scientific research in this field would require annual investment of 2 billion USD. These would be public goods: assets that benefit the entire population.

In 2015 the UN passed a resolution to adopt several SDGs, which include a pledge to eliminate TB by 2030. This is a source of hope and expectation: that there will come a day when we will finally have peace of mind, when we can feel safe in the knowledge that that this infectious disease that has plagued us for thousands of years has finally been consigned to history.