Diseases Are Smarter Than Our Meds

Everyone Will Be Sick in the Drug-Resistant Future

By Bruno Bayley

Here in the West, we’ve gotten used to having effective medications for common ailments available at our fingertips. The bad news is that many of these medicines will soon cease to work. This is because the pathogens responsible for some of the world’s more horrifying diseases—many of which appear to have been largely eradicated—have continued to mutate and develop resistances since the development of their supposed cures.

Because I’m an obsessive hypochondriac, I had to know more about this impending biological disaster so that I can spend the interim wallowing in the comfort of a constant state of panic. To help me get there, I spoke with Rachel Nugent, who chaired the Drug Resistance Working Group and Initiative while at the Center for Global Development, about her research into horrific diseases and the treatments that will, someday soon, be completely ineffective. 

VICE: Why are medications we spent so much time and money developing now failing?
Rachel Nugent: There are a number of ways a pathogen can develop a resistance to drugs. One is when people who are taking drugs, the right drugs, don’t finish the full course. Maybe after a few days they start feeling better, so they see no reason to continue taking the medicine. You have to put pressure on the bug to kill it, but it doesn’t work if it’s incomplete. It’s like you’re having a fight in a boxing ring, you have the bug on the ropes, and then you walk away thinking you’ve won. Well, that bug can come back, and often it comes back stronger. This is called “acquired resistance,” which means the pathogen adapts within the person’s body to be less susceptible to the meds. The second way resistant strains propagate is when an already-resistant form of pathogen spreads from one person to another, or from animal to human. The more this resistant strain is spread around, the more common it becomes.

Are resistant forms of pathogens considered new strains? Are they the same thing? 
Yes, usually, but resistance is not always the result of mutations. It can result from other ways the microbe adapts to its environment. Also, mutations happen all the time and don’t always lead to resistance. Generally speaking, infectious disease is the area where we most need to worry about resistance, although it can also apply to cancer drugs, for instance. But because the whole process is so much slower when treating diseases like cancer, we don’t see resistance building at the same pace as we do for infectious diseases.

So the rapid mutation of infectious-disease pathogens also accelerates their level of drug resistance?  
Yes. They can change at a rate of hundreds or even thousands of mutations an hour. They can also adapt in other ways that allow them to survive in the presence of drugs. Malaria, for instance, is very difficult for us to control. We’ve developed a number of new drugs for malaria, but the parasite that causes it adapts very quickly and efficiently. We can’t keep up with it. We have a lot of antibiotics available, but many are similar to one another, so each pathogen that mutates or adapts in response to one type of antibiotic will more easily acquire resistance against a number of others. 

Over the course of my finger-gnawing research for this interview, I discovered that tuberculosis is one of the main case studies in the fight against drug-resistant bacterial diseases. What makes TB such a worry? I thought we had it under control. 
TB is a great example of a way that resistance to drugs develops, because a person needs to be on TB medication for a long time to cure it. With a normal case of TB, an individual might be taking medication for around nine months. Over the course of treatment, there’s plenty of opportunity to slip up and forget or neglect to take the meds. And TB drugs are nasty; people don’t want to be on them. But in the case of TB, the medical system has responded pretty well. We usually observe TB patients, using a method we call Directly Observed Therapy Short-Course, to ensure that they take their meds at the prescribed intervals. Nine months may seem like a long time, but if someone is unfortunate enough to get stuck with a resistant strain of TB, he or she will have to take meds for at least a couple of years. 

How prevalent is this super-resistant form of TB?
It’s out there, and it’s widespread. Treatment for it is one of the worst drug regimens available, and it’s much more expensive than normal TB drugs. There are some forms of TB around now that we really can’t treat at all. The drugs we have don’t seem to cure it. We call it totally resistant TB, although that is not an official term yet. The term used for other forms of resistant TB is either multidrug-resistant TB (MDR-TB) or extensively drug-resistant TB (XDR-TB). Totally resistant TB is not widespread, but people don’t like to talk about it. 

Do cheap and counterfeit meds manufactured in the East contribute to the drug-resistance dilemma? 
Yes, and this is where India, China, and other sources of poor-quality drugs become important. It’s not just a matter of a poor health system, which many of these countries have, but there’s also the issue of substandard drugs. These are drugs that work, feel, or even act like good antibiotics or good antimalarials, but oftentimes they are produced in factories that skimp on the active ingredients, or they are produced in a high-quality way but are degraded somewhere along the supply chain. Both counterfeit and substandard drugs are a threat and can lead to resistance, but of course a drug that is completely counterfeit isn’t going to include the active ingredient in it at all, so it won’t contribute to resistance. It’s having too little of that active ingredient in the drug that allows the bug to survive the pressure.

Mind you, not all drugs manufactured in India or China are substandard or counterfeit. But the amount of bad drugs flooding into poor countries, and even some richer countries, is staggering. And just as new medications flow around the world, drug-resistant bugs are very good travelers. 

A close-up of Neisseria gonorrhoeae bacteria scattered among white blood cells. If you have these little guys inside you, you probably have gonorrhea, and if they’re the drug-resistant kind, you’re fucked. 

I recently read about a form of super-gonorrhea that is, as of now, untreatable. I believe it was first reported among sex workers in Japan.
Gonorrhea is something that we haven’t really worried about for decades; it was quickly and easily cured with antibiotics. But we are now seeing these new strains of gonorrhea and some of the other sexually transmitted infections. These can be pretty damaging diseases if left uncured. 

What about HIV/AIDS medications? Are they also slowly becoming obsolete? 
This is actually one case where we can say resistance is ahead of us; it’s off in the future. It’s happening slowly, being documented at pretty low rates—less than 5 percent of cases seem to be resistant forms. That’s still pretty low, but if we’re spending money to put a patient on antiretrovirals (ARVs), and we aren’t paying attention to the management of the drugs and how people are adhering to regimens, then it will become a big problem too. Think about all the research-and-development money put into creating ARVs, which were developed to combat HIV. We need as many as we can get. We are clearly losing many of the antibiotics we have, and have lost many, if not all, of the antimalarials we have. 

What happens when antimalarials no longer work? Are we all going to die from mosquito bites? 
We are now seeing resistance to all malaria treatments, even artemisinin-combination therapies, which are formulations of multiple drugs combined into one pill. Artemisinin has been the only truly effective agent against malaria until recently, and it has been useful to combine it with other antimalarials because drugs work differently, or have different mechanisms of action. Making the pathogen fight against several mechanisms is more effective than pitting it against just one. You might have heard of drug cocktails used to fight AIDS. It’s the same principle.  

Why don’t the old antimalarials work?
Until recently, all we had to treat malaria was old drugs like sulfadoxine/pyrimethamine and chloroquine, which date back to the 50s. The longer most drugs are used, the greater the likelihood that some resistance will develop over time. That’s why the increased use of ARVs around the world is expected to result in even more resistance. 

So is there any hope for people who have been infected with these drug-resistant strains? 
With TB, there is nothing to be done but to treat them with second- or third-line drugs. Second- and third-line drugs are your backups. They’re more expensive, typically have worse side effects, and require more advanced health facilities to administer. For some diseases, we don’t even have backups. But people can also just die, and they do. 

Illustration by Sam Taylor

Photo by CDC/Joe Millar

Bring a box of tissues and read more from our Hopelessness Issue:

The Secret Drinker’s Handbook

Don’t Get Caught

The Right to Die Is the Right to Live