Tracking malaria by DNA passport

30 May 2019

Interview with 

Bryan Greenhouse, University of California San Francisco

BITING-MOSQUITO

The image shows a mosquito biting a human.

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Malaria is a scourge in many poorer countries. It can be controlled with interventions like bed nets, spraying and education. But which of these you use depends upon where the malaria is coming from in any given geography. If most of the problem’s an imported one, giving everyone a bed net just wastes money and doesn’t make a dent in the disease. But finding out where most of the cases are coming from has always been very difficult: people give vague histories, the resolution of sampling’s quite low, and even tracking people using mobile phone data is frustrated by international borders. But now, speaking with Chris Smith, Bryan Greenhouse explains how he and his colleagues have a new weapon: the disease’s DNA passport...

Bryan - What we think we've got here is a much better way to understand how malaria moves around in Africa. We're limited right now - in terms of understanding how malaria moves - by basically asking people where they've moved. The problem with asking people is that they may not remember; they may not tell the truth even if they do remember. And even if they do tell us the truth, we may not understand exactly where the parasites that they've been infected with are coming from. So when people come in with malaria, they may or may not know where the mosquito that bit them came from. But the malaria parasites themselves carry a passport, essentially, of everywhere they've been. And that passport is their DNA. So by looking into the DNA of the malaria parasites, we can actually trace where those parasites have come from - whether or not the person who's been infected has any idea where they came from.

Chris - And is that what you did? You actually got the malaria that the person was carrying, and interrogated it genetically?

Bryan - Yeah, it sounds complicated, but actually in terms of what we did in the field it was relatively straightforward. When people get tested for malaria they get a drop of blood taken from their finger usually, and it's put on either a microscopy slide or a rapid diagnostic test. And essentially what we did, for half of this study, was just collect those used cassettes from the test that's already been done, got the parasite DNA off of those cassettes, and then compared them to the DNA from other people that had malaria. And the other half of this study, it was very similar: we just got a drop of blood on a piece of filter paper as part of another study, and extracted the parasite DNA off of that. By doing a DNA fingerprint from these different types of samples we collected, comparing them across hundreds of different samples, we were able to see how malaria was moving around in this part of southern Africa.

Chris - If you've got just the genetic fingerprint of the malaria parasite, how do you actually know geographically where it came from then?

Bryan - That's a great point. The DNA itself is not enough information. You need to know at least some framework of where other parasites’ DNA are coming from. So in this study we had malaria infections coming from something like 30 different health facilities across northern Namibia. And by putting all that information together - where the people came from, and the information that they provided on where they've been - we were able to infer how these parasites are connected to each other and moving around in this part of Africa.

Chris - Are there any other data sources that we can plug into in the modern era? Because you know having travelled across southern Africa myself quite extensively, I was very surprised when I first did that, that I could actually browse the Internet faster than I can at home. Can you trace where people go by where the mobile phones are going?

Bryan - Absolutely. And that's what the state of the art has been up until now, before we started integrating genetics. So the really interesting thing about mobile phones is, every time you turn on your mobile phone,or it connects to a cell tower, that information is recorded by the mobile phone company. As you're walking around with a mobile phone, and you move from one cell tower to another, the mobile phone company actually has information about your movement at some level, in terms of what cell towers are connected to. By taking those data in a very anonymised way, we can get a general sense of how people are moving around. And what we did in this study was: we compared the estimates we had about how malaria was moving from the mobile phone data, to the data that we got from the travel history and genetics. And it was very interesting in that, over some scales - very short scales - we found similar things. So both mobile phone data and the genetic data indicated that a lot of the transmission of malaria was occurring over very short scales - say, a kilometer, the distance a mosquito can fly. But what the mobile phone data missed was that there are also very substantial connections of parasites moving over longer distances within a single country - Namibia, which is the country we focused on most here - as well as between countries. One of the limitations actually of the mobile phone data is that, for the most part, these companies are national; and so it is currently very difficult to trace how people are moving across borders using mobile phone data. And that is one of the most important questions with respect to malaria.

Chris - And if you bring all of this together - I presume, understanding the constraints of one prior measure, the strengths of your new measure - you can begin to understand the disease dynamics a lot more. And that has to be key to trying to control, and ultimately eliminate, the disease from these different geographies.

Bryan - That's absolutely right. We have a limited amount of money to spend on interventions to try to reduce and eliminate malaria. And so we need to be smart about how we put these interventions in place. If malaria is just coming in from somewhere else, but not really spreading locally, we shouldn't really be wasting a lot of money by giving out bed nets, or doing more spraying in the area where the cases are popping up, if they're not actually being transmitted there. On the other hand, if the malaria is spreading quite a bit locally and we have evidence to support that, then we want to be very aggressive in trying to reduce the amount of mosquitoes and trying to eliminate malaria transmission in the area where we're in.

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