Blunting The Force Of Disease Is Complicated

7:59 minutes

This story is a part of Science Friday’s coverage on the novel coronavirus, the agent of the disease COVID-19. Listen to experts discuss the spread, outbreak response, and treatment.

COVID-19 vaccines are highly effective at preventing severe disease. But their efficacy in lab-controlled trials may not exactly correlate to how well they work in the real world.

David Kaslow, chief scientific officer at the global public health nonprofit PATH, explains that a factor known as the “force of infection” plays a role in determining how well vaccines work. The force of infection describes the attack rate of a pathogen—the amount of time it takes a susceptible individual to get infected in a given population. 

In a study recently published in the academic journal NPJ Vaccines, Kaslow and his colleagues found that in vaccine trials for rotavirus and malaria in Africa, efficacy could vary widely between two trial sites. When there were many infections in the community, the overall efficacy of the vaccines appeared lower than in communities where disease incidence was low. 

While the same sort of studies haven’t yet been done on the coronavirus outbreak, Kaslow argues that similar factors may be at play now—pointing to a continued need for non-pharmaceutical measures to control transmission, from masking to social distancing. 

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Segment Guests

David Kaslow

David Kaslow is Chief Scientific Officer at PATH, based in Seattle, Washington.

Segment Transcript

ROXANNE KHAMSI: This is Science Friday. I’m Roxanne Khamsi. Ira Flatow is off this week. Later in the hour, some food for thought as the US heads towards Thanksgiving.

But first, there’s been a lot of attention given to the numbers around vaccine efficacy and they are impressive. But how well do the numbers they come up with in a careful clinical trial match the numbers in real-world conditions? A vaccine’s real-world performance may be tied to something called the “force of infection”, which is related to how long it takes for a susceptible person to get sick in a population.

Joining me now to talk about that is David Kaslow, Chief Scientific Officer for PATH, a global public health nonprofit. He wrote about this recently in the journal Nature. Welcome.

DAVID KASLOW: It’s great to be here, Roxanne.

ROXANNE KHAMSI: So David, can you start us off by just helping us understand what’s the basic definition here of force of infection?

DAVID KASLOW: So force of infection, the technical definition is the rate at which susceptible individuals in a population acquire an infectious disease in that population over a period of time. Think of it as the attack rate or the incidence rate. How many people are being infected over a certain period of time.

ROXANNE KHAMSI: When this pandemic all started, we heard a lot about something called R-Naught. How is this different?

DAVID KASLOW: They’re related to one another. So R-Naught is a measure of the transmissibility of a particular pathogen, in this case, the SARS-CoV-2 virus. So how many people does a single infected person pass that infection on to? That’s the R-Naught.

The force of infection is the other side of the equation, which is how many people does a susceptible individual need to contact before they become infected? So different side of the equation. One is who’s transmitting it. The other one is who’s getting infected.

ROXANNE KHAMSI: It’s really interesting. So if there’s more virus around me because we’re– now the force of infection is centered around the susceptible person. So if there’s more virus around me, I’ve got a bigger chance of getting infected and getting sicker?

DAVID KASLOW: That’s right. And so that’s called the infectious dose. So how many viruses do you need to be exposed to before you get infected? And does that dose determine how severe disease you have? And there’s some evidence to suggest that that infectious dose– kind of the level, the exposure level– does have an influence on how severe the disease you get once you become infected.

ROXANNE KHAMSI: It sounds like with force of infection, the infectious dose matters a lot. But why is that?

DAVID KASLOW: In short, infectious dose matters because it determines in part whether or not an infection can take hold; determines in part how severe the disease will be; and it determines in part how well the vaccine will protect you particularly against infection and mild to moderate disease.

ROXANNE KHAMSI: The viral dose we get matters even if we’re vaccinated?

DAVID KASLOW: It does, Roxanne, and the reason for that is it’s a numbers game. So let’s say you have 1,000 viruses that you’re exposed to. Your immune system at that time has only a certain capacity. So let’s say you’ve got 1,000 viruses you’re exposed to. You got one or two tanks to fire on those.

If the infectious dose is higher than 1,000, you can overwhelm your defense system, you can overwhelm your tanks, and the virus can take hold. So the lower that we can keep that exposure to the virus, the better chance your immune system, those tanks, and those planes have to block the virus from getting through.

ROXANNE KHAMSI: And is the idea that that infectious dose isn’t the same everywhere we go? Is it variable?

DAVID KASLOW: It is variable. And that’s what’s really described in that paper that you referenced. And what’s been observed is that vaccine efficacy varies depending on where you are. I mean that tells, it gives us a clue as to force of infection as a determinant of what your risk of infection is.

ROXANNE KHAMSI: So in these vaccine trials, there are measures in place to mitigate the spread of the coronavirus. Are they kind of too idealized? Like how does apply to what we know from vaccine trials and the real world?

DAVID KASLOW: And that’s one of the problems but also one of the strengths of a Phase III trial. They’re very well controlled. So you try to use the utmost standard of care. In the case of SARS-CoV-2, making sure that people are physical distancing, wearing a mask, good hand hygiene, et cetera, et cetera. So you’re measuring the vaccine efficacy or how well the vaccine works in an ideal situation. The problem is that may not reflect what’s going on in the real world.

And what was observed in this and published in this paper is that when you look at different forces of infection, you see a difference in vaccine efficacy. So the highest efficacy was observed in the places where there were the lowest cases of that disease. In one case, malaria, the other case, Rotavirus in those settings. And the lowest vaccine efficacy was seen in the settings where there was the highest rates of infection in the control group.

ROXANNE KHAMSI: So you studied this force of infection phenomenon using malaria as one of the examples. Based on what you saw, does it mean that even community to community, you’ll see different performance and vaccine efficacy in the real world?

DAVID KASLOW: Exactly right, Roxanne. So what was observed in that malaria trial, it was a Phase III trial run in 11 research centers in seven different African countries. And what we saw was just under 45% efficacy in one setting. And in another setting, we saw over 80%. And so what was observed is was the highest efficacy of 80% was seen in the setting with the lowest attack rate. In that case, it was three cases per 100 children. And we saw the lowest efficacy just under 44% when the attack rate was 300 cases per 100 children.

ROXANNE KHAMSI: And have we seen this play out with the COVID vaccines as well?

DAVID KASLOW: Don’t know that we have really good data to be able to do the type of comparison that was done in this Phase III trial of malaria. It was a single trial over 11 different research centers. So that data has not been observed in the same way with SARS-CoV-2. But I think there’s some evidence to suggest that vaccine efficacy could vary depending on the force of infection.

ROXANNE KHAMSI: So what’s the take-home lesson for the public here? This isn’t just something of interest as disease modelers? Right? Does this matter for the everyday person, this whole concept of force of infection?

DAVID KASLOW: I think this force of infection does matter. And the reason why it does matter is this, and it’s widely known, that the vaccine efficacy may wane over time. Part of the reason why it may wane over time is your immune system starts to decay a bit.

But it could also be because we have different variants of concern which have a higher force of infection. And so how can we mitigate that higher force of infection? We can go back to some of the public health and social measures that we used previously to try to reduce the force of infection, which should improve the vaccine efficacy.

ROXANNE KHAMSI: Wow. Well, this is definitely something I’ll be thinking about as we head into the holidays and we’re exposed to potentially new social situations, and things like that. But this is super fascinating. Thank you so much.

DAVID KASLOW: Thanks, Roxanne.

ROXANNE KHAMSI: David Kaslow is Chief Science Officer for the global public health nonprofit, PATH.

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About Charles Bergquist

As Science Friday’s director and senior producer, Charles Bergquist channels the chaos of a live production studio into something sounding like a radio program. Favorite topics include planetary sciences, chemistry, materials, and shiny things with blinking lights.

About Roxanne Khamsi

Roxanne Khamsi is a science writer based in Montreal, Quebec.

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