Zika virus laser treatment: shining a light on the mosquito problem
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Mosquito-borne viruses can ravage nations, but researchers hope to stop the next Zika-like outbreak with lasers.
Summer is mosquito time and for more than a billion people across the world every year, this means debilitating pain, blindness, brain damage or possibly death. Well-known mosquito-transmitted diseases include dengue fever, malaria, the West Nile virus, yellow fever and, following the horrific outbreak of 2015 and 2016, Zika.
Yet as mosquito populations relentlessly rise, physicists, entomologists and mosquito-borne disease researchers are stepping in with a host of optics-based technologies to improve surveillance and eradicate outbreaks.
In May this year, Dr Maggy Sikulu-Lord, from the University of Queensland, Australia, and colleagues revealed they had used infrared light to detect the Zika virus in mosquitos, 18 times faster and 110 times more cheaply than today’s painstakingly slow and expensive standard – quantitative reverse transcription polymerase chain reaction (RT-qPCR).
She says: “We just use a benchtop spectrometer with external probes and direct the light beam at the mosquito... we can tell if it is infected in 10 seconds.”
Near-infrared spectroscopy (NIRS) has been used for decades in agriculture, pharmaceuticals and medicine to classify biological samples based on type and concentration of chemical compounds in the sample. However, prompted by the rise in mosquito-borne diseases, Sikulu-Lord as well as researchers at the renowned Ifakara Health Insitute, Tanzania, and UK-based Institute of Biodiversity, Animal Health & Comparative Medicine, Glasgow University, have been investigating the method to characterise mosquito species.
Sikulu-Lord’s latest Zika detection breakthrough promises to be a lifesaver. Having reared Aedes aegypti mosquitos in their laboratory, the entomologist and her colleagues fed half with Zika-infected rabbit blood and the other half with virus-free blood.
Four, seven and ten days later, mosquitos were killed and then scanned, using NIRS, with distinctly different spectra generated. Sikulu-Lord says her method has been shown to be between 94 and 99 per cent accurate compared to RT-qPCR, and is now searching for Zika-infected insects in Korea, so she can test her method on ‘true’ specimens.
She also has high hopes the method will be adopted by the World Health Organisation for surveillance in countries where Zika is endemic and is assessing the effectiveness of NIRS on mosquitos carrying dengue and malaria.
“Our main goal is to find the virus hot-spots quickly and more effectively,” she says. “In the future we want to develop smaller handheld spectrometers that can be used to scan mosquitos in the field and I would also like funding bodies to set up centres to process NIRS data sent in from countries with budget restrictions.”
Yet you don’t necessarily have to get close to a mosquito to analyse it. As early as the 1970s, researchers have been using lidar – pulsed laser-based detection which works on the principle of radar – to measure atmospheric processes. Here, a laser is transmitted into the atmosphere with detected backscattered light providing information on, say, aerosol distribution, greenhouse gas concentrations, cloud base heights and more.
Then, in the last decade, a handful of physicists adapted the optical remote-sensing system to measure the wing beat frequency, body and wing size of large insects, including moths, dragonflies and honey bees, to distinguish different species. So-called entomological lidar typically uses at least one infrared, continuous laser to interrogate insects, with one or more telescopes collecting the backscattered light. The wing beat frequency can then be retrieved by applying, for example, a Fourier transform on the recorded signal.
Fast-forward to the last couple of years, and several laser-based systems have been applied to mosquitos to discriminate these flying menaces not only on species but also gender: so very important as only females can transmit disease. Indeed, Professor Benjamin Thomas from New Jersey Institute of Technology, USA, recently used his continuous-wave infrared optical remote-sensing system, in a controlled laboratory environment, to reliably distinguish male and female mosquitos in species that transmit yellow fever, dengue fever, Chikungunya fever and the Zika virus.
“Female mosquitos have a very different wing-beat frequency to the males, so you can identify females very specifically – our system has retrieved gender with 96.5 per cent accuracy,” says Thomas. “We’re now also improving the accuracy at which we can identify different species – we’ve reached more than 75 per cent in the lab – and will be retrieving even more optical properties in the next couple of months.”
Thomas is certain his laboratory-based system can be reliably used in the field to analyse mosquitos within a 100m range by increasing the size of the collecting optics, using, say, a Newtonian telescope with a large primary mirror. Importantly, such systems provide a speedy and easy alternative to the mosquito traps used to monitor insect populations.
While almost 100 per cent accurate, these traps rely on pheromones, food or carbon dioxide as bait and are tedious to set up with extensive coverage being overwhelmingly labour-intensive. What’s more, the trapped mosquitos then have to be individually counted and identified in a laboratory, a painstakingly slow procedure.
“These laser approaches may be less accurate now, but you can monitor a much larger number of mosquitos in real time, and get more data that provides good statistics on the ecosystem you are looking at,” says Thomas. “Every time a mosquito transits through the laser beam, you can identify it, and out on the field we can potentially analyse around 100 insects an hour.”
‘The data analysis behind the hardware in particular is very complex... but this isn’t science fiction, we can do this.’
Mikkel Brydegaard from the Lund Laser Centre, Lund University, Sweden, is a long-standing pioneer of entomological lidar and has devoted his career to developing systems to characterise biological lidar targets such as plankton, migrating birds and flying insects, including mosquitos. In his words: “It is a challenge to estimate wing-beat frequency in a robust way.”
However, he and colleagues have forged ahead with multi-band modulation spectroscopy methods and a novel lidar based on a 19th-century photography concept devised by Captain Theodor Scheimpflug.
To correct perception distortion in aerial photographs, the Austrian army captain invented a novel camera set-up, in which the lens plane did not lie parallel to the image plane. One century later, and as part of a lidar system, Brydegaard and colleagues combined this principle with continuous wave infrared lasers and CMOS detector arrays to implement remote modulation spectroscopy with high sensitivity and resolution in space and time, in principle faster than the round-trip of light.
“We’ve been making high-resolution Scheimpflug and other systems with ranges up to a couple of kilometres that have time- and space-resolution way beyond anything you see from other atmospheric lidars,” he says. “For example, we have lidar that is sensitive enough to pick up molecular backscatter from the atmosphere itself.”
Crucially for mosquito management, the lidar system can sample tens of thousands of flying insects an hour, so Brydegaard and collaborating biologists have been using the systems to understand insect flight activity, and importantly, determine the sex and species of mosquitos in flight.
“[Discriminating] between mosquito sex has been easier than species,” he says. “We can look at body size, wing size, melanisation and have been [considering] if we could differentiate the females with and without bloodmeal.”
As part of this research a Lund University spin-off company, Denmark-based Fauna Photonics, has been busy carrying out several field campaign assignments and developing software for Brydegaard’s flavour of lidar, in a bid to monitor mosquitos and other pests in real time for public health and agricultural markets.
Indeed, in recent field studies in Tanzania, Brydegaard, fellow researchers and Fauna Photonics colleagues used a 1km-range lidar to profile the activity of Anopheles mosquitos – which can carry malaria – measuring the size and wing-beat frequency of these insects.
As Michael Stanley Pedersen, chief executive of Fauna Photonics, points out: “This was a ground-breaking way of studying the behaviour of these mosquitos. We looked at how these insects swarmed as well as the interactions between males and females, which is normally so very difficult.
“People seem to think our systems are science-fiction; shining light over an open area to measure wing-beat frequency, insect glossiness, number of legs and so on,” he adds. “The data analysis behind the hardware is very complex, but this isn’t science fiction, we can do this and we’re now seeing a lot of traction with this technology.”
Where next for the rapidly developing world of mosquito-borne disease detection? The New Jersey Institute of Technology’s Thomas, for one, believes optical systems such as his and lidar-based set-ups could be used in tandem with traditional mosquito traps, and even Zika-detecting NIRS such as Dr Sikulu-Lord’s, from the University of Queensland. As he points out, systems such as his cannot yet detect if a mosquito is carrying an infectious disease, but these methods can. So combine the two systems and you have an accurate means of monitoring and pinpointing potentially deadly mosquitos.
For Thomas, such a move can’t happen soon enough. As he points out, climate change is altering the global distribution of insects, and researchers are struggling to keep up. “Look at Zika; that virus was always one step ahead of us, we only knew where the mosquitos were from the clinical reports of the sick, and we had no idea how far north it had reached,” he says.
“Yet data from these remote optical-monitoring systems will allow us to precisely monitor the distribution of key species,” he adds. “Today aerosol lidars are used in every city to monitor so many activities, and my goal is to demonstrate that our instruments can be used by, say, mosquito-control associations to do the same.”
Fauna Photonics’ Pedersen has similar aspirations. His company is “in dialogue” with key public health players including Switzerland-based Vestergaard and the Bill Gates Foundation, and hopes to form industrial partnerships to take the company’s lidar technologies further.
“Eventually I would like to see thousands of instruments taking measurements and sharing data to inform local authorities of a potential disease outbreak,” he says. “We could map this data, work out how disease migrates around the world, how resistance builds up and provide better interventions for the benefit of mankind.”