Despite the chaos they cause, the good news is that eventually, outbreaks come to an end. How long the outbreak lasts, and the amount of harm it does in that time can both be reduced by the efforts we take and the resources we have access to. One of the vital tools of an outbreak response is vaccines, which, under the right circumstances, can stop the spread of a disease and end an outbreak. But even once its outbreak is over, our job isn’t done. Things don’t go back to normal straight away, especially for those who might need help in dealing with the aftermath of such a difficult time. So in this episode, we’ll predict the future and discuss how outbreaks end, how vaccines can help that process, and what issues communities face after an outbreak.

 I’m Pardis Sabeti and this is Crash Course Outbreak Science!

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 So, how do we know when an outbreak of infectious disease is over? An obvious answer is “when the disease has stopped spreading.” After all, if no one is getting infected, the outbreak must have stopped! While that’s definitely one potential end case of an outbreak, it’s not the only one. To see why, it helps to revisit the definition of an outbreak. We’ve learned that it’s when an infectious disease infects many more people than would be expected in a certain group. So for an outbreak to come to an end, the situation has to reverse. The rate at which new cases of people with the disease appear, called the incidence, will start dropping. Sometimes, it’ll drop all the way to 0. If the global rate reaches 0 for long enough, then we say the disease is eradicated-- we’ll never get it again.

So far, only smallpox has been eradicated for humans. But incidence might not -- and frequently does not -- go all the way to zero, even in smaller outbreaks. Instead, the incidence might drop to a lower, steady rate. Often, that’s similar to what the incidence was before the outbreak, like the short-lived outbreak of cholera we looked at in the Ganges Delta in episode one. The rate of new cases started off small, then jumped up during the outbreak and finally, gradually fell back down to the original level. But sometimes, the disease might become endemic when it wasn’t before.

Before the twentieth century, HIV wasn't an infectious disease that affected humans, and we didn't identify it until the 1980s. But after the global pandemic of HIV in the eighties and nineties, while the total number of new infections every year fell from its peak, HIV became persistent in many regions of the world, with only small changes in incidence over time. So in general, outbreaks end when the incidence falls to a steady rate, which may or may not be zero. That tells us something important: even after an outbreak is over, the disease might continue to have an impact. We might need ongoing supplies of certain resources, like drugs and treatments, and behavioral shifts, like self isolating when we have symptoms of the disease.

Whether the pathogen is gone for good or stubbornly hanging round, the end of an outbreak tends to come about in one of two ways. One, if the outbreak is caused by a reservoir in the environment where pathogens lurk and can spread to humans, like infected food and water or a population of insects, then ending the outbreak involves getting away from that source or getting rid of it. For instance, during the famous London cholera outbreak in 1854, some people in the neighborhood moved away from the infected water pump, and then epidemiologist John Snow decided to break the handle off. Both methods kept people away from the source of the outbreak. And two, if the outbreak is caused by a disease that is transmitted person-to-person, which we call a contagious disease, then ending the outbreak involves limiting transmission between people. That happens when infected people go on to infect less that one person on average-- in math modeling terms, this is when R is less than one. At that point, with each new round of infections, fewer people become infected than the last time, until the outbreak is over. One of the best ways we can make the rate of infections go down is by intervening, or doing something to stop the transmission of pathogens-- basically, all of the strategies we’ve been talking about throughout this series!

For example, we can stop outbreaks of bacterial diseases like syphilis by using antibiotics such as penicillin. But the incidence can fall even when we don’t intervene. It might fall because the pathogen simply has fewer places to go. If a pathogen has already spread significantly throughout a community, many people will already have become infected. And, as we learned when looking at the immune system, being infected by a particular pathogen means that, at least in the short term, we’re unlikely to catch it again. In other words, we become immune. Naturally, as more people become immune, it becomes harder for the pathogen to spread until eventually, the incidence of the disease begins to drop. If enough people are immune to a disease, then a pathogen’s spread will be so limited that even people without individual immunity won’t be infected, preventing future outbreaks!

 This is called herd immunity. It’s like when there’s not enough fuel for a fire to keep going so the flame dies out. The pathogen doesn’t have enough susceptible people to keep infecting, so it stops spreading. While that sounds great, in many cases, natural herd immunity relies on a lot of people becoming infected, getting sick, and even dying, which is the very thing we want to avoid! Additionally, it can take a long time for a pathogen to naturally circulate to enough people for the population to develop herd immunity. That could give a pathogen time to mutate and escape our immune defenses. Thankfully, for some diseases, especially those caused by viruses, we don’t have to wait around for natural herd immunity, thanks to vaccines.

The goal of most vaccines is to help our adaptive immune system, the part of our immune defense that responds to specific pathogens, learn to recognize a pathogen and create antibodies that will fight against the real thing. They do this by showing our immune system some part of the pathogen, like a wanted poster that they can reference in the future. But different kinds of vaccines do this in different ways.

 Let’s go to the Thought Bubble.

 Many vaccines involve introducing a weakened or dead version of a pathogen into the body, which are called whole pathogen vaccines. This sounds similar to just giving someone a disease, and that is how early vaccines started out-- but using a weak or dead pathogen rather than the real thing is very different, not to mention much safer! These kinds of vaccines defend us against diseases like Hepatitis A, Measles, Mumps and Rubella. Other kinds of vaccines don't need the whole pathogen to stimulate your body’s immune response. Instead, they just introduce the proteins on a pathogen’s surface, called antigens, or harmless versions of the toxins a pathogen would produce. These kinds of vaccines are known as sub-unit vaccines, since they use only bits of a whole pathogen. They help prevent diseases like whooping cough and tetanus.

Finally, we can also make vaccines that don’t even need bits of the pathogen, but only the instructions for making those bits. These vaccines use a part of a pathogen’s genetic sequence that codes for the antigens on their surfaces. This teaches our own cells how to create those antigens, which are harmless compared to the actual pathogen, but still trigger the immune response that prepares the body to respond to the antigens on the real thing, like a sub-unit vaccine. As of 2021, these vaccines use genetic sequences from a pathogen’s RNA, the part of an organism’s genetic material that carries instructions for proteins and may use DNA in the future. Since both DNA and RNA are made up of nucleic acids, those vaccines are known as nucleic acid vaccines. While the technology has been under development for a long time, these types of vaccines have only been made available recently, most notably as vaccines to prevent COVID-19.

 Thanks Thought Bubble!

In all of these cases, the immune system might need some extra familiarity with the pathogen or its identifying material, meaning that some vaccines need to be given more than once to work effectively. These are known as boosters. The upshot of all of this is being able to give individuals immunity --without getting them sick --, which in turn gives groups herd immunity. As a result, vaccines save millions of lives every single year from outbreaks of tetanus, whooping cough, the flu and measles that never even happen in the first place. Sometimes, when the circumstances are right, we can even eradicate a disease, which is what awe did for smallpox!

But creating a vaccine is an enormous challenge of its own. For starters, we haven’t always figured out a way to create a vaccine for a given disease--yet! Even when we do, they need a lot of testing to make sure they’re safe and effective in lots of different kinds of people, which involves running large-scale clinical trials. And as part of that, we need to understand the people who might get a vaccine, what diseases they might be exposed to, and how their different immune systems will respond. Still, creating a safe, working vaccine might not be enough on its own.

Pathogens evolve over time and change their genetic material and antigens in the process, meaning that new vaccines might need to be developed each year for the same disease-- that’s why we’re told to get our flu shot every year. Finally, from the time and research needed to make a vaccine, to the infrastructure needed to deliver them, creating vaccines is, frankly, expensive. So sadly, without financial incentives, some pharmaceutical companies won’t want to research and develop vaccines. That’s where governments and other organizations can step in to provide resources like funding, incentives, and even their own research.

For instance, in 2001, Canada’s public health agency funded a laboratory which began developing a vaccine for Ebola, since it’s the kind of virus with the potential to spiral from a small outbreak into a global pandemic, or even be weaponized and used in a bio-terrorism attack. By the time an Ebola outbreak happened in West Africa in 2014, they had a vaccine ready to go and were able to offer one thousand doses to help tackle the outbreak. But in general, as we’ve seen for many aspects of handling outbreaks, the inequality between communities and countries with and without resources, determines who has access to vaccines, and the resilience against outbreaks they offer. And while vaccines and other interventions like antibiotics might help us end an outbreak, there’s also things to deal with after an outbreak, even when the disease has stopped spreading.

 For starters, while the pathogen itself can make people sick, not everyone recovers to full health again. Serious infections can have lasting effects on the body. For instance, after the SARS epidemic in 2003, some patients had long term effects from the disease like persistent coughs, trouble breathing, as well as lung or kidney disease. After-effects like this can result from the pathogen itself damaging our organs, or from our own immune systems reacting so aggressively to the pathogen that they hurt our own bodies. There are long-lasting mental health issues to consider too. For instance, healthcare workers are often pushed to their limits during an outbreak and need support afterwards to process potentially traumatic and overwhelming experiences. The same is true for those who provide informal care to infected people, like family members of people with an illness, during an outbreak. And the rest of the community might also struggle to deal with the fallout of an outbreak. They too need to process the effects of dealing with life-altering interventions, the fear of falling ill, or losing loved ones. So like we consider the need for extra healthcare capacity during an outbreak, we need to think of the needs for healthcare and community support after an outbreak. We should provide resources to help people cope with their experience, and adapt to life post-outbreak.

After enduring an outbreak, it’s also natural to ask what could be done to stop it happening again. Approaching this question is essential for coming up with strategies that reduce the odds of further outbreaks, which is why we’ve studied them throughout this series. So in our next and final episode, we’ll see how we as individuals can use what we’ve learned to help tackle outbreaks head on.

We at Crash Course and our partners Operation Outbreak and the Sabeti Lab at the Broad Institute at MIT and Harvard want to acknowledge the Indigenous people native to the land we live and work on, and their traditional and ongoing relationship with this land. We encourage you to learn about the history of the place you call home through resources like native-land.ca and by engaging with your local Indigenous and Aboriginal nations through the websites and resources they provide.

Thanks for watching this episode of Crash Course Outbreak Science, which was produced by Complexly in partnership with Operation Outbreak and the Sabeti Lab at the Broad Institute of MIT and Harvard— with generous support from the Gordon and Betty Moore Foundation. If you want to help keep Crash Course free for everyone, forever, you can join our community on Patreon.