Why are we Still Fighting Tuberculosis?

This piece was completed for a graduate-level science writing class that I took at DePaul.

King Tut, Edgar Allan Poe, Eleanor Roosevelt, and George Orwell all lived in various times across human history, yet they all died the same way- of tuberculosis, the highly contagious but treatable disease. Tuberculosis, or TB, is an age-old disease, often associated with eras of the past. If you are watching a historical drama and you notice that your favorite character is subtly coughing drops of blood into their handkerchief, odds are they have contracted tuberculosis.

However, tuberculosis is not a thing of the past. In fact, TB is still on the rise around the world. In 2014, 1.5 million TB-related deaths occurred worldwide. Because of both antibiotic resistance and the rise of AIDS, tuberculosis has become a critical problem in developing countries with few medical resources, the World Health Organization estimates that one-third of the world’s population is infected with latent TB. This urgent global epidemic receives little attention in the media, yet devastates nations. While we ignore the problem, it only becomes a bigger threat. However, scientists in recent years have been searching for better treatment options in the face of this growing problem.

Tuberculosis reached epidemic proportions in the 18th and 19th centuries, and was identified as a bacteria (tubercle bacillus) in 1882. Formerly known as ‘consumption’ because it would cause its victims to lose weight, this bacterial disease presents with a fever, and a cough often accompanied by blood or sputum. Although there are hundreds of strains of TB, they all present the same symptoms that have been seen for hundreds of years. The trouble with these various strains are that some respond to the current available tuberculosis treatment well, and some do not.

One of the reasons this disease is so hard to treat is that research about TB has been on the backburner for many developed countries, since few cases are seen in Europe and the United States. “The numbers are highest in China and India because of their large populations,” says Dr. Bill Bishai, Co-Director of the Center for Tuberculosis Research at Johns Hopkins University. From his prestigious position, he can see why the research on TB is lacking. “There’s not a public outcry, it’s not in the newspapers, U.S. taxpayers aren’t demanding a solution,” he says. “It has to do with public awareness and money.” While in the United States we are not worried about this disease, it is gaining epidemic proportions in other parts of the world, and new strains are running rampant because of increasing resistance to antibiotics.

Antibiotic resistance is becoming a growing concern in the medical community. Overuse of antibiotics has led to the unintentional breeding of stronger, more resilient bacteria, which is harmful in the long run. The same thing happens when we try to kill bacteria with antibiotic drugs. In fact, the first evidence of drug-resistant strains of tuberculosis began appearing only a few years after the drug treatments were discovered. “It’s a very slowly mutating organism,” says Dr. Bishai.

The nature of the treatment seems to give tuberculosis a lot of time to adapt. “It takes 6 months under optimal circumstances to cure someone who has drug-susceptible TB,” says Dr. Bishai. The treatment process involves taking four different drugs for two months, and then two drugs for the following four months. This obviously causes problems for people in countries where doctors are hard to come by, Bishai explains. “We can’t reliably be sure individuals take their medicine for six months, let alone maintain drug stocks.” Because it takes so long to cure a person of TB, it is no wonder than the disease is always one step ahead.

To understand why TB made such a strong comeback, you have to understand its relationship to HIV. With patients who are immunocompromised, TB can again become an extremely deadly disease. In the 1980s, when AIDS first appeared as a major global health crisis, TB quickly became the number one most common infection among patients with AIDS. Because of HIV, TB was able to spike sharply worldwide for the first time since the invention of antibiotics. Since then, the rate of TB has been declining with the rate of HIV.

But the battle is far from won. The decline of TB has been slowing down in the past few years in the U.S., while also becoming an increasing threat in developing countries. Meanwhile, there is an obvious lack of interest in this disease from the general public. “It’s not very lucrative,” Bishai says. “Pharmacies aren’t interested in TB. We are using drugs that are 60 or 70 years old. We wouldn’t be treating for six months if we had modern medicines. The antibiotics we use to treat TB came out in the 40s and 50s.” We have a lot of catching up to do if we are going to stop the spread of tuberculosis, but the latest medical research might bring us closer to a cure.

Among the biggest advances in biology of the last few decades, particularly in the field of medicine, is the ability for scientists to sequence the genomes of organisms. Identifying the genetic building blocks of each known strand of the Tuberculosis-causing bacteria could be our first step in creating ‘personalized medicine’. For now, it helps scientists understand the very basics of TB. “I’m a believer in basic science, if we figure out how TB does what it does, we can figure out what medicines to use,” says Bishai. “We don’t really have a blueprint for how TB makes people sick.” He is particularly interested in understanding how the TB bacterium causes inflammation in human cells. “It’s like hijacking an airplane. We don’t know everything, but it definitely interferes with cell signaling,” says Bishai.

In fact when compared to other infectious diseases, we know very little about TB. The University of Illinois in Chicago is doing important work with the most drug-resistant strands of TB in the world. Dr. Nina Wolf is doing post-doc work with the Institute of Tuberculosis Research there. Her work begins with enzymes in TB bacteria (Fructose Bisphosphatase, to be precise) that begin the harmful reactions that harm the human body. She and her associates work to find out what compounds might be able to shut down these enzymes and render the TB bacteria harmless.

The laboratory tests compounds from the most exotic sources. “Other groups at UIC get the samples from the deep sea, the tropics, areas that we know very little about, because these ecosystems are very different,” says Dr. Wolf, a young woman with wide blue eyes and a meticulous demeanor. “A lot of different bacteria in soil and other places excrete natural antibiotics to protect themselves from other bacteria.” Compounds such as these are being tested by the UIC lab, and other top laboratories around the world. “Our group has a big collaboration with the Tuberculosis Alliance, we share a lot of information back and forth with them,” says Wolf.

One valuable tool that makes the UIC research efforts unique is that they have a Biosafety Level 3 laboratory, which means that the lab can keep samples safely isolated in a controlled environment. “You wear a respirator, full protective wear, and even if you open the door, there is negative pressure that would keep the air inside,” says Dr. Wolf. The Biosafety Level 3 designation allows the lab to do work with deadly strains of TB, with little risk of contamination.

UIC’s work with Tuberculosis isn’t a concern for the average American. “When I first tell people that I work with TB, they say, ‘I thought that was eradicated!’” she says. “I am surprised at how little research is really being done, there have only been a few drugs going through clinical trials in the last 40 years.” This perception of TB and the dismissal of its importance by the pharmaceutical industry definitely causes most of the developed world to forget about the millions of people diagnosed with TB today.

There does exist a vaccine for TB, but it isn’t very effective. It only reduces your chance of fighting off the disease by a certain amount, and can only reliably be used on infants who may get TB, it has little effect on adults. “It’s not as simple as just giving everyone the vaccine,” says Dr. Wolf, “and the latent TB is also a big problem.” Even if we cured every person who was sick from TB, in order to truly eradicate the disease, we would need to find a way to eliminate the latent bacteria from that one-third of the population.

For the time being, scientists in institutions (rather than scientists in for-profit industries) like Dr. Bashai, Dr. Wolf, and their associates are slowly making progress. “There has been some work for search on new combinations of known drugs that might be helpful,” Dr. Bashai explains, and also mentions, “there are a couple in clinical trials that look like they are going to help.” Dr. Wolf also confirms that her lab at UIC recently released a drug in phase I clinical trials. However, a new viable treatment for TB might still be years away, and nothing is certain.

We only see Tuberculosis as a distant problem, affecting impoverished people in Africa, Asia, and India. If diseases received attention from researchers and scientists based on the number of people they affected, the epidemic might be over. Unfortunately, the industry chooses diseases to target based on the amount of money they would make. Since TB is a disease that most often affects the poor in hard-to-reach areas of the developing world, companies have no interest in discovering new medicines to help those people. In the end, it’s certainly possible that developed countries will pay for this oversight. If drug-resistant bacteria continues to spread, our outdated antibiotics need help to catch up in time.

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