Lurking in the skin

14 November 2016

Interview with

Annette MacLeod, University of Glasgow

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African sleeping sickness or "trypanosomiasis" is one of a list of topical illnesses that the World Health Organisation wants to stamp out and a they've set an ambitious target to cut cases to under 1 in 10,000 of the population in 90% of the areas that are affected.Trypanosomes-in-skin-cartoon

But new research from Glasgow parasitologist Annette MacLeod, suggests that there might be a tsetse fly or two  in the ointment, because she's discovered a formerly unrecognised reservoir of the infection, lurking in the skin of apparently healthy people...

Annette - African trypanosomes are protozoan parasites that cause the foetal disease human African trypanosomiasis or sometimes known as African sleeping sickness. This is found in sub-Saharan Africa and it is transmitted from person to person by the bite of a tsetse fly when it takes a blood meal. A number of cases of sleeping sickness has gone down in recent years due to concerted efforts by the WHO and national control programs to try and control the disease. A number of cases has dropped below 10,000 for the first time in 50 years. But we've been here before. In the 1960s, the number of reported cases was below 10,000 and then we took our eye off the ball and the disease re-emerged and it peaked up at 300,000 in the 1990s. Now, we have the disease under control again. The important thing is not to let the disease re-emerge. But there are still these stubborn pockets of disease that just won't go away. We need to understand how the parasite has escaped the elimination before so we can stop it doing it again.

Chris - Where do you think it might be lurking?

Annette - Well, we think there are some people that have lower numbers of parasites in their blood and they have no symptoms. These people are missed by the screening process but they are infected. Evidence suggests that they are able to transmit the disease. The question is how.

Chris - I guess then so, where are the parasites lurking in those people? if they are not in the blood, where are they?

Annette - That's a crucial question and that's what we have discovered. We have discovered a hidden reservoir of these parasites hiding in the skin. These skin-dwelling parasites can be picked up when the tsetse fly takes a blood meal and so, spreads the disease.

Chris - I guess everyone had assumed that because these insects are drinking blood, that must be the crucial route through which anything gets transmitted into the fly. But if the parasites are in the skin, in the course of getting to the blood, that's when they might be picking them up.

Annette - Yes, because tsetse flies have serrations along their proboscis that actually makes a mess of the skin and the tsetse bite is quite sore. It feeds on the pool of blood and lymph that collects as it bites.

Chris - People talk about this being slash and suck, don't they?

Annette - Yes, that's right. It's a slash and suck kind of insect.

Chris - And so, if these trypanosomes are sitting there in the skin as this serrated mouth part goes through then it could draw in the parasites via that route.

Annette - That's right.

Chris - How do you know this is happening? How did you find this?

Annette - Well, what we did, we had fairly simple experiments where we label the parasites and then we used different live in-vivo imaging technologies to observe where the parasites go.

Chris - When you said "label", how?

Annette - We have them expressing of fluorescent tag so that they glow red or green. What we found is that we could follow these parasites in a live animal over time.

Chris - Do you think this is relevant to what's happening in these people because obviously, you're not doing this in people, you're doing this in experimental animals so, do you think that's a good representation of the human equivalent?

Annette - Yes. First of all, we looked in mice. We found that the parasites were in the skin of mice. We found that these skin-dwelling parasites in mice could be transmitted to tsetse flies when we fed tsetse flies on the mice. And some mice have very low parasitemia. So that means they had very low numbers of parasites in their blood. But they did have skin-dwelling parasites. And these skin-dwelling parasites were able to infect the tsetse flies. Obviously, you can't do these experiments in humans but we managed to obtain skin biopsies for over a thousand people living in an endemic focus in the Democratic Republic of Congo. We looked in these biopsies for the parasites. We found people that had parasites in their skin. And these people had not been diagnosed before. They had not been diagnosed as having sleeping sickness. They didn't have clinical signs and they didn't seem to have any parasites in their blood.

Chris - But crucially, does the bug respond to the same treatment one would meet out to somebody who has parasites in their blood or in the skin? In other words, if we can find it, we can just get rid of it.

Annette - That's something that hasn't been tested before. We've not tested the current drugs to see if they can eliminate the skin-dwelling parasites. But that is a crucial step that we must do. And if any new drugs come along, we must make sure that they are able to kill these skin-dwelling parasites, as well as the blood parasites. So current policy is not to treat people with asymptomatic infections, but we think that it needs to be reconsidered in the light of these individuals that can persist and transmit the disease.

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