Drug kills mosquitoes when they feed through ingestion and surface contact
Liverpool School of Tropical Medicine
A drug that makes human blood lethal to mosquitoes also acts as a potent contact insecticide absorbed through the feet, providing a promising new approach to combating insecticide resistance.
A new study led by Liverpool School of Tropical Medicine shows that mosquitoes are killed when they feed on blood and then land on a surface sprayed with nitisinone, a drug currently used to treat a rare genetic condition in humans.
The research shows that this is true even when the mosquitoes are highly resistant to existing insecticides, which opens a promising new avenue for formulating nitisinone for indoor spraying or bed nets at a time when resistance poses a significant threat to vector control programs worldwide.
Nitisinone is lethal to mosquitoes as it blocks an enzyme that they need to safely process the protein and amino acids they get from blood.
The new paper, published in Parasites & Vectors, follows on from a study earlier this year that showed that nitisinone is deadly to mosquitoes when they drink the blood from someone on nitisinone therapy. The drug is safe and already approved for widespread human use and is currently the only treatment for the rare genetic disorders tyrosinemia type 1 and alkaptonuria.
In this new study, nitisinone was shown to be mosquitocidal to several mosquito species (Anopheles, Aedes and Culex), including those that transmit malaria, reemerging infections such as dengue and Zika, and emerging viral threats like Oropouche and Usutu viruses.
The research also proved that nitisinone killed mosquitoes regardless of whether exposure occurred before or after a blood meal, tapping into mosquito resting behaviour before or after feeding. Because nitisinone works by disrupting the mosquito’s bloodmeal digestion (tyrosine metabolism), which is not a pathway targeted by any of our current insecticides, it could help public health campaigns eliminate mosquitoes where insecticide resistance has made other products fail.
Dr Lee Haines, senior author and Honorary Research Fellow at LSTM said: “Our conclusions are exciting. Working with a drug like nitisinone, and its versatility, bodes well for creating new products to combat mosquitoes. The fact that it effectively kills insecticide-resistant mosquitoes could be a game-changer in areas where resistance to current insecticides is causing public health interventions to fail.
“This project proved how important it is to think outside the box. We don't know yet why nitisinone is absorbed through the mosquito's feet, and why the other similar compounds are not. But it is going to be exciting to solve this mystery!”
Zachary Stavrou-Dowd, Research Assistant and PhD student at LSTM, and lead author on the new paper, said: “Nitisinone acts to clog up the mosquito digestive system. When a mosquito gorges on your arm, that blood contains a massive protein load. What we have shown here is that we can turn that key trait against them. The mosquito can't digest the blood; it becomes overloaded by its own meal; it dies."
The research was part funded by the Jean Clayton Fund for early career researchers at LSTM.
Zachary Stavrou-Dowd said: "Receiving the Jean Clayton Early Career Researcher Award at LSTM was a pivotal moment, it not only helped fund part of this study but also strengthened our application for a Rosetrees Seedcorn Grant. It’s a great example of how internal support can catalyse external funding opportunities and boost visibility for early career researchers like me.”
Journal
Parasites & Vectors
Subject of Research
Animals
Article Title
The β-triketone, nitisinone, kills insecticide-resistant mosquitoes through cuticular uptake. Parasites Vectors
New network to address malaria among school-aged children in sub-Saharan Africa
A new network aims to improve malaria prevention among school-aged children in sub-Saharan Africa.
The new partnership, led by Liverpool School of Tropical Medicine and funded by Open Philanthropy, will unite researchers, policymakers, healthcare practitioners and other stakeholders across multiple countries to better understand and address the burden of malaria in children.
Malaria is the leading cause of death in primary school-aged children in sub-Saharan Africa, and infection rates peak in this age group. Despite this, there is no routine surveillance data for this group, so the societal and health systems costs are not well understood.
In many countries, surveys have shown more than 50% of ‘asymptomatic’ school children are infected with malaria parasites. These chronic infections are associated with anemia and decreased learning, as well as serving as the main source of community transmission, which undermines malaria elimination efforts.
The new network, including collaborators in health and education across Africa, will identify and help fill knowledge gaps as well as develop guidance and tools to support countries in determining how to address the burden of malaria in school-aged children.
Through coordination across new studies, evidence synthesis, knowledge exchange, and engagement with policy makers, the network aims to improve the understanding of the scale of malaria in school-aged children to improve the quality of evidence generated on individual and community benefits of reducing malaria in school-age children, aid decision-making about resource allocation, and elevate the profile of the impact of malaria control interventions targeting this age group.
Dr Lauren Cohee, Reader in Paediatrics and Child Health at LSTM and lead of the new network, said: “More than 200 million African school-age children are at risk of malaria. In highly endemic areas, school-age children often experience more than one episode of malaria infection or disease each and every year. These infections lead to decreased well-being, missed opportunities for learning, and economic burdens on families and health systems. In the context of shrinking investments in global health research and development assistance, we must also figure out how to do more with less.
"This network is an exciting opportunity to come together as a community to determine where, when, and how to address the burden of malaria in school-age children to support children and communities to achieve their full potential.”
The new initiative follows an initial stakeholder engagement meeting last year, including representatives from eight sub-Saharan African countries and 30 organisations, focused on understanding and addressing malaria in school-aged children.
Attendees noted the need for a network to enhance knowledge exchange and collaboration among the growing community of researchers, policymakers, programme managers, implementing partners, and funders committed to understanding and addressing the burden of malaria in school-aged children.
No comments:
Post a Comment