No more blood tests, now life-saving light beam to detect malaria

A fast, needle-free malaria detection tool developed by a University of Queensland-led team could help save hundreds of thousands of lives annually.

Malaria is usually detected by a blood test, but scientists have devised a method using a device that shines a beam of harmless infrared light on a person’s ear or finger for five-to-10 seconds, it collects an infrared signature that is processed by a computer algorithm.

International team leader, Dr Maggy Lord from UQ’s School of Biological Sciences, said the technology would revolutionise how malaria is fought globally.

The malaria detection tool collects an infrared signature for a mobile phone to process./CREDIT:The University of Queensland

The malaria detection tool collects an infrared signature for a mobile phone to process./CREDIT:The University of Queensland

“Currently it’s incredibly challenging to test large groups of people, such as the population of a village or town – you have to take blood from everyone and mix it with a reagent to get a result,” Dr Lord said.

“But with this tool we can find out very quickly whether a whole village or town is suffering from, or carrying, malaria.

“The technique is chemical-free, needle-free and detects malaria through the skin using infrared-light – it’s literally just a flash on a person’s skin and it’s done.

“The device is smart-phone operated, so results are acquired in real time.”

The researchers believe the technology is the first step to eliminating malaria.

mosquito

Tiger Mosquito of Asia is adaing to survive the state of Illinois’s harsh winters / CREDIT: JAMES GATHANY/CDC

“According to the World Health Organisation malaria report, in 2020 there were an estimated 241 million cases worldwide and more than 600,000 died from malaria,” Dr Lord said.

“Most of the cases are in sub-Saharan Africa, where 90 per cent of deaths are children under five years old.

“The biggest challenge in eliminating the disease is the presence of asymptomatic people in a population who act as a reservoir for transmission by mosquitos.

“The World Health Organisation has proposed large-scale surveillance in endemic areas and this non-invasive, affordable and rapid tool offers a way to achieve that.”

The technology could also help tackle other diseases.

“We’ve successfully used this technology on mosquitoes to non-invasively detect infections such as malaria, Zika and dengue,” Dr Lord said.

“In our post-COVID world, it could be used to better tackle diseases as people move around the globe.

“We hope the tool could be used at ports of entry to screen travellers, minimising the re-introduction of diseases and reducing global outbreaks.

“It’s still early days, but this proof-of-concept is exciting.”

UQ collaborated with the Instituto Oswaldo Cruz, Brazil, led by Dr Rafael Maciel de Freitas, who applied the tool to detect malaria in patients in the Amazon region.

The work was funded by Fiocruz INOVA Ideias Inovadoras, Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico, Fundação Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro and by Advance Queensland Industry Research Fellowship and the National Health and Medical Research Council.

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Scent, sweat from human skin attract disease-spreading mosquitoes

Scent, sweat from human skin attract disease-spreading mosquitoes

Mosquitoes that spread Zika, dengue and yellow fever are guided toward their victims by a scent from human skin. The exact composition of that scent has not been identified until now.

A UC Riverside-led team discovered that the combination of carbon dioxide plus two chemicals, 2-ketoglutaric and lactic acids, elicits a scent that causes a mosquito to locate and land on its victim. This chemical cocktail also encourages probing, the use of piercing mouthparts to find blood.

This chemical mixture appears to specifically attract female Aedes aegypti mosquitoes, vectors of Zika as well as chikungunya, dengue, and yellow fever viruses. This mosquito originated in Africa, but has spread to tropical and subtropical regions worldwide, including the U.S.

Mosquitoes use a variety of cues to locate their victims, including carbon dioxide, sight, temperature, and humidity. However, Cardé’s recent research shows skin odors are even more important for pinpointing a biting site.

Aedes aegyptii mosquito biting a person./CREDIT CDC

“We demonstrated that mosquitoes land on visually indistinct targets imbued with these two odors, and these targets aren’t associated with heat or moisture,” Cardé said. “That leaves skin odor as the key guiding factor.”

Given the significance of odor in helping mosquitoes successfully feed on humans, Cardé wanted to discover the exact chemicals that make our scent so potent for the insects. Part of the equation, lactic acid, was identified as one chemical element in the odor cocktail as long ago as 1968.

Since then, several studies have identified that carbon dioxide combined with ammonia, and other chemicals produced by humans also attract these mosquitoes. However, Cardé, who has studied mosquitoes for 26 years, felt these other chemicals were not strong attractants.

Methods that chemists typically use to identify these chemicals would not have worked for 2-ketoglutaric acid, Cardé said. Gas chromatography, which separates chemicals by their molecular weight and polarity, would have missed this acid.

“I think that these chemicals may not have been found before because of the complexity of the human odor profile and the minute amounts of these compounds present in sweat,” said chemist Jan Bello, formerly of UCR and now with insect pest control company Provivi.

Searching for mosquito attractors, Cardé turned to Bello, who extracted compounds from the sweat in his own feet. He filled his socks with glass beads and walked around with the beads in his socks for four hours per odor collection.

Credit: MINDY TAKAMIYA/KYOTO UNIVERSITY ICEMS

“Wearing the beads felt almost like a massage, like squeezing stress balls full of sand, but with your feet,” said Bello. ‘The most frustrating part of doing it for a long time is that they would get stuck in between your toes, so it would be uncomfortable after a while.”

The inconvenience was worth the investment. Bello isolated chemicals from the sweat deposited on the sock beads and observed the mosquitoes’ response to those chemicals. In this way, the most active combination emerged.

Future studies are planned to determine whether the same compound is effective for any other mosquitoes, and why there is such variation in how individuals are apt to be bitten. “Some are more attractive than others to these mosquitoes, but no one’s yet established why this is so,” Cardé said.

Though this discovery may not lead to insights for the development of new repellants, the research team is hopeful their discovery can be used to attract, trap, and potentially kill disease-spreading mosquitoes.

Making mosquitoes self-destruct

Researchers at the University of California, Riverside have developed transgenic mosquitoes that stably express the Cas9 enzyme in their germline. The addition of Cas9 will enable the use of the CRISPR gene editing tool to make efficient, targeted changes to the mosquitoes’ DNA.

As proof of concept, the researchers used the system to disrupt cuticle, wing, and eye development, producing completely yellow, three-eyed and wingless mosquitoes. Their long-term goal is to use Cas9-expressing mosquitoes together with another technology — called gene drives — to insert and spread genes that suppress the insects while avoiding the resistance that evolution would typically favor. Aedes aegypti are major carriers of dengue, chikungunya, yellow fever, and zika viruses, and are rapidly becoming resistant to commonly used pesticides.

Published today in the Proceedings of the National Academy of Sciences (PNAS), the study was led by Omar Akbari, an assistant professor of entomology in UCR’s College of Natural and Agricultural Sciences and a member of the university’s Institute for Integrative Genome Biology.

Previous efforts to use genome editing to prevent mosquitoes from spreading pathogens have been hampered by low mutation rates, poor survival of edited mosquitoes, and inefficient transmission of disrupted genes to offspring. Akbari and colleagues developed transgenic mosquitoes that stably express a bacterial Cas9 enzyme in the germline, enabling highly efficient genome editing using the CRISPR system. CRISPR works like a pair of molecular scissors, cutting out and replacing specific DNA sequences based on a ribonucleic acid (RNA) guide. In the paper, the team used the system to disrupt genes that control vision, flight and feeding, resulting in mosquitoes with an extra eye, malformed wings, and defects in eye and cuticle color, among other changes.

Akbari said these strains represent the first step toward using gene drive systems to control mosquito populations and reduce the diseases they spread.

“These Cas9 strains can be used to develop split-gene drives which are a form of gene-drive by which the Cas9 and the guide RNA’s are inserted at separate genomic loci and depend on each other for spread. This is the safest way to develop and test gene drives in the laboratory to ensure no spread into the wild,” Akbari said.

Gene drives greatly increase the odds that a gene or set of genes will be passed on to offspring — from 50 percent to 99 percent. This number can potentially increase to 100 percent when a target gene is disrupted in multiple sites, a technique called multiplexing that has recently been mathematically modeled by Akbari and colleagues at UC Berkley.

Gene drives can be used to bias genetic inheritance in favor of rapidly spreading, self-destructive genes — such as those that disrupt fertility — and could be an environmentally friendly and cost-effective way to suppress populations of disease-spreading insects.

“Next steps should be undertaken to identify the regulatory sequences that can be used to express the guide RNAs from the genome, and once these sequences are identified developing gene drives in the species should be turnkey,” Akbari said.