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In the opening of HBO’s The Last of Us, a couple of scientists on a 1960s-era interview show debate the possibility of a fungus-driven pandemic destroying humanity. It not only sets the tone for the show, it makes you wonder if something like that could actually happen. The answer: No. At least, not right now. In the future, though, it’s a possibility.

This got me thinking about what kind of infection is most likely to ravage humanity and destroy our way of life in the coming years. The contenders: Bacteria, viruses, and fungus. Each has an impressive historical kill-count and its own strengths and weaknesses. Here’s how they stack up.

The case for a fungal pandemic

Fungal infections are mostly a nuisance. The most common examples in the U.S.—ringworm, nail infections, yeast infections, and thrush—are easily treatable with common medications and are generally cured within a few weeks. But some types of fungal infections that are more serious. Diseases like fungal meningitis and bloodstream infections, though not common, are potentially deadly, especially for immunocompromised people. And the emergence of new kinds of fungal infections is a definite possibility in the future.

How fungal infections spread

Minor fungal infections tend to spread person-to-person through direct contact and through contact with fungi in damp areas—it’s why you get athlete’s foot at the gym—but fungus doesn’t spread in the same way viral and bacterial infections do. Infected people don’t breathe out clouds of spores that others breathe in to become clickers. While we definitively breathe in a ton of fungal spores all the time, they’re fairly harmless to most of us.

Instead of person-to-person spread, fungal disease outbreaks happen when people breathe in a common source of fungal spores. For instance, the soil in the southwestern United States and parts of Mexico and Central and South America is teaming with the fungus that causes Valley Fever. Most people who breathe in Valley Fever spores don’t get sick, and if they do, it’s with a cough that goes away in a few weeks. But for older people, infants, and other susceptible people, it can be a serious condition.

But all that could change at any time. Most pathogenic fungi can’t deal with the heat inside our bodies and that keeps us safe, but some research suggests these pathogens are evolving as our planet warms, and our body heat might not be enough to fight them off forever. Luckily, fungal spores are much larger than viruses, so if everyone wore a mask, it wouldn’t be a problem. I’m sure there wouldn’t be an issue with that.

The bottom line: Fungal disease apocalypse is unlikely in the near future, but it is something to keep an eye on.

The case for a bacterial pandemic

Bacterial infections are the OGs of worldwide deadly disease outbreaks. Cholera, anthrax, tuberculosis, and a host of other disastrous maladies are caused by bacteria, including the bubonic plague that wiped out as many as 200 million people in Europe, Africa, and Asia in the 1300s—arguably the worst plague ever, in terms of percentage of the population killed.

How bacterial infections spread

Bacteria are good at traveling and they are everywhere. While the vast majority of bacteria just do their thing and don’t harm us, the deadly ones make their way to us through air, water, food, surface contact, animals, and probably our wicked thoughts.

That’s the bad news. The good news is that most bacterial infections can be cured through antibiotics. The first antibiotic, penicillin, was introduced in the 1920s and led to many more that we use to treat bacterial diseases. Once major health scares, like syphilis, have all but disappeared thanks to antibiotics. Should you be unlucky enough to catch the Black Death in 2023 (there are an average of seven cases per year in the U.S.), as long as you’re treated with antibiotics, you’ll probably come out fine and have a cool story to tell. Even a deadly disease like Anthrax has a 55% survival rate if treated. But of course that’s not the end of the story.

Over time, antibiotics have become less effective. Bacteria have been evolving to become resistant to known antibiotics, probably because they are over prescribed to people and livestock, leading to the resurgence of some diseases like tuberculosis, as well as “superbugs” that seem immune to any antimicrobial agents. In the United States an estimated 35,000 people die from antibiotic-resistant infections per year, and that number is likely to increase with time.

The bottom line: Do not discount the chances of an antibiotic resistant super-bacteria from taking out humanity.

The case for a viral pandemic

The effects of a virus that causes a deadly disease spreading throughout humanity are all around us all the time, so I won’t belabor the point, except to point out why viruses are so insidious. Unlike bacteria or fungi, viruses aren’t alive, at least not in the same sense that other organisms are alive. Because they are not among the living, it’s more difficult for us to make them among the dead (if only technically). Antibiotics basically work by attacking bacteria’s cell walls, blocking protein production and stopping reproduction. Viruses hijack our own cells to replicate, so we can’t target them in the same way we can target bacteria.

How viruses spread

Viruses spread in basically the same way bacteria do, and common viral infections even mimic the symptoms of bacterial infections (hence the overuse of antibiotics). Not only are they immune to antibiotics, viruses are 100 times smaller than bacteria, so they spread more easily—and they evolve more quickly too.

They might not be technically alive, but viruses still undergo the evolutionary processes of natural selection and genetic mutation, and they do it in novel ways. This is why the flu shot changes every year. Besides ordinary types of mutations, here’s another fun thing they can do: If two viruses infect the same cell, it’s thought that they can swap genetic material and create a new virus.

There is good news, though. The only human disease we’ve completely wiped from the face of the earth, smallpox, was caused by a virus, and other once fearsome viral diseases— polio, measles, tetanus, etc.—are uncommon. The white knights in all these cases were vaccines. We might have trouble attacking viruses directly, but vaccines can “teach” our immune systems to do the job and thus prevent infection and spread in the first place, provided enough people actually take the vaccines, but I’m sure that won’t be a problem.

So what’s going to cause the next pandemic and kill us all?

Judging by the speed of the development and implementation of the COVID-19 vaccine, I like to think viral infections will be less of a problem in 100 years—if we get there. But in the immediate future, more worldwide more viral pandemics are all but inevitable, so if I had to put my money on the disease that will kill us all, I’d guess it will be caused by a virus.



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