No flight, no bite: 'Mosquito grounding' bed net nearly halves malaria infection in Tanzanian children: First new insecticide for 40 years that's shown to be safe and effective for use on nets could save many young lives - Science Daily | Canada News Media
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No flight, no bite: 'Mosquito grounding' bed net nearly halves malaria infection in Tanzanian children: First new insecticide for 40 years that's shown to be safe and effective for use on nets could save many young lives – Science Daily

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A novel class of bed net that kills mosquitoes resistant to traditional insecticides by making them unable to move or fly, significantly reduces malaria infection in children, according to new research published in The Lancet.

Unlike other insecticides which kill the mosquito via the nervous system, the effects of the new bed net mean the mosquito dies from starvation or being unable to fend for itself.

The two-year community randomised trial involved more than 39,000 households and followed over 4,500 children aged 6 months to 14 years in Tanzania. It found that a long-lasting insecticidal net treated with two insecticides, chlorfenapyr and pyrethroid (chlorfenapyr LLIN), reduced the prevalence of malaria by 43% and 37% in the first and second year respectively, compared to the standard pyrethroid only long-lasting insecticidal net (LLIN).

Chlorfenapyr LLIN also reduced clinical episodes of malaria by 44% over the two years and the number of malaria-infected mosquitoes captured by 85%.

The study was conducted by the London School of Hygiene & Tropical Medicine (LSHTM), National Institute for Medical Research, Kilimanjaro Christian Medical University College in Tanzania, and the University of Ottawa, Canada.

Long-lasting insecticidal nets are the cornerstones of malaria control in sub-Saharan Africa. However, in the past few years the decline in malaria has stalled and even reversed in some countries. In 2020, there were 627,000deaths from malaria, mainly in Africa and occurring mostly in children.

Malaria’s resurgence is partly due to the bed nets’ effectiveness being compromised by widespread resistance to pyrethroid insecticides in Anopheles mosquitoes. Chlorfenapyr works very differently to pyrethroid, causing wing muscle cramps that stop the flight muscles from functioning. This prevents mosquitoes from making further host contacts or biting, ultimately leading to their death.

The research team says the novel net could lead to significant malaria control gains in sub-Saharan Africa, but more research is needed to examine feasibility of scale-up, and on resistance management strategies needed to preserve their effectiveness long term.

Dr Jacklin F. Mosha from the National Institute for Medical Research, Tanzania, the study’s first author, said: “Malaria remains a huge problem across sub-Saharan Africa and is one of the leading causes of death in Tanzania. We urgently need new interventions to get control efforts back on track and protect young people from this deadly disease. These exciting results highlight that we have another effective tool to help control malaria.”

Children from 72 villages in Misungwi, where high levels of resistance to pyrethroids have been reported, were randomised into groups and received one of three of the most promising new generation of bed nets. Children were then tested for malaria at the end of each rainy season.

After 24 months, malaria infection was reduced by 37% in children that received the chlorfenapyr LLIN (326/1272) compared to those receiving standard pyrethroid LLIN (549/1199).

A bednet treated with a piperonyl butoxide (PBO) to enhance the potency of pyrethroid reduced malaria infection by 27% over the first 12 months of the trial, but after two years malaria infection in this group was similar to the standard net. This is likely due to it being used less regularly as holes appeared in this net more quickly.

A third type of bednet, treated with pyrethroid and pyriproxyfen which sterilises female mosquitoes, had little additional effect compared to the standard pyrethroid net. The reason is not fully understood but likely due to insufficient pyriproxyfen remaining on the net over time.

Dr Manisha Kulkarni, a scientist at the University of Ottawa’s Faculty of Medicine, said: “By essentially ‘grounding’ the mosquito, our work on adding chlorfenapyr to standard pyrethroid bed nets has great potential to maintain control of malaria transmitted by resistant mosquitoes in Africa.”

The higher costs of the chlorfenapyr LLIN were offset by the savings from reducing the number of malaria cases requiring treatment. Distributing chlorfenapyr nets is therefore expected to cost households and society less overall than standard, PBO, or pyriproxyfen nets.

Dr Natacha Protopopoff, from LSHTM and study Principal Investigator, said: “We’ve shown chlorfenapyr LLINs are safe, decrease malaria infection in children and are cost-effective. This is important evidence for the World Health Organization and malaria control programmes when they are assessing whether these new nets should be deployed in areas of insecticide resistance when standard bed nets have failed.

“However, caution is needed. The massive scale-up of standard pyrethroid LLINs 10-20 years ago led to the rapid spread of pyrethroid resistance. The challenge now is to preserve chlorfenapyr’s effectiveness by developing rational resistance management strategies.

“National malaria control programs and stakeholders should urgently advocate for better textile and insecticide durability for all novel classes of bed nets to maximise their longevity and potential.”

LSHTM scientists first identified the potential of the chlorfenapyr insecticide on malaria mosquitoes almost 20 years ago. The chlorfenapyr LLIN was subsequently developed by the manufacturer BASF in Germany, together with LSHTM.

Professor Mark Rowland, from LSHTM, explained: “When it comes to resistance to standard nets we were running out of options, but chlorfenapyr has come to the rescue. Although it may appear this has happened overnight, in reality there were twists and turns over many years to show how the new class of insecticide truly works ,to develop improved formulations to confirm effectiveness and safety on nets, and finally to demonstrate control of malaria in large scale trials.

“What really threw us for a long time was that in daytime tests the chlorfenapyr was not very toxic to the mosquito, but at night when the malaria mosquitoes naturally fly up against the treated bednet it gets a severe case of muscle cramps so it buckles and falls to where it is likely to be carried off by scavenging ants. No other mosquito insecticide works like this, and because of the unique mode of action it kills all kind of mosquito that have evolved resistance to other insecticides. It should have a long future.”

Professor Franklin W. Mosha, Principal Investigator from the Kilimanjaro Christian Medical College, Tanzania, said: “This achievement has only been made possible through partnership between research institutes, manufacturing industry and funding agencies like the Bill & Melinda Gates Foundation and then the Innovative Vector Control Consortium We can all take pride in our respective roles in getting us to this exciting point.”

The authors acknowledge limitations of the study, including the rapid decrease in use of trial LLINs, within a context of high overall net usage, which may in part explain the relative lack of effectiveness of PBO LLINs and pyriproxyfen LLINs over the two years compared to standard LLINs.

This is the first of two trials of chlorfenapyr nets. The second in Benin in West Africa with the Centre de Recherche Entomologique de Cotonou and LSHTM is due to report later this year. This will confirm if chlorfenapyr LLINs are also more effective in a different malaria setting and if pyriproxyfen LLINs could perform better when net usage is higher.

The research was funded by the Joint Global Health Trials: Foreign, Commonwealth and Development Office, Medical Research Council, Wellcome and Department of Health and Social Care.

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Whooping cough is at a decade-high level in US

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MILWAUKEE (AP) — Whooping cough is at its highest level in a decade for this time of year, U.S. health officials reported Thursday.

There have been 18,506 cases of whooping cough reported so far, the Centers for Disease Control and Prevention said. That’s the most at this point in the year since 2014, when cases topped 21,800.

The increase is not unexpected — whooping cough peaks every three to five years, health experts said. And the numbers indicate a return to levels before the coronavirus pandemic, when whooping cough and other contagious illnesses plummeted.

Still, the tally has some state health officials concerned, including those in Wisconsin, where there have been about 1,000 cases so far this year, compared to a total of 51 last year.

Nationwide, CDC has reported that kindergarten vaccination rates dipped last year and vaccine exemptions are at an all-time high. Thursday, it released state figures, showing that about 86% of kindergartners in Wisconsin got the whooping cough vaccine, compared to more than 92% nationally.

Whooping cough, also called pertussis, usually starts out like a cold, with a runny nose and other common symptoms, before turning into a prolonged cough. It is treated with antibiotics. Whooping cough used to be very common until a vaccine was introduced in the 1950s, which is now part of routine childhood vaccinations. It is in a shot along with tetanus and diphtheria vaccines. The combo shot is recommended for adults every 10 years.

“They used to call it the 100-day cough because it literally lasts for 100 days,” said Joyce Knestrick, a family nurse practitioner in Wheeling, West Virginia.

Whooping cough is usually seen mostly in infants and young children, who can develop serious complications. That’s why the vaccine is recommended during pregnancy, to pass along protection to the newborn, and for those who spend a lot of time with infants.

But public health workers say outbreaks this year are hitting older kids and teens. In Pennsylvania, most outbreaks have been in middle school, high school and college settings, an official said. Nearly all the cases in Douglas County, Nebraska, are schoolkids and teens, said Justin Frederick, deputy director of the health department.

That includes his own teenage daughter.

“It’s a horrible disease. She still wakes up — after being treated with her antibiotics — in a panic because she’s coughing so much she can’t breathe,” he said.

It’s important to get tested and treated with antibiotics early, said Dr. Kris Bryant, who specializes in pediatric infectious diseases at Norton Children’s in Louisville, Kentucky. People exposed to the bacteria can also take antibiotics to stop the spread.

“Pertussis is worth preventing,” Bryant said. “The good news is that we have safe and effective vaccines.”

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AP data journalist Kasturi Pananjady contributed to this report.

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The Associated Press Health and Science Department receives support from the Robert Wood Johnson Foundation. The AP is solely responsible for all content.

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Scientists show how sperm and egg come together like a key in a lock

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How a sperm and egg fuse together has long been a mystery.

New research by scientists in Austria provides tantalizing clues, showing fertilization works like a lock and key across the animal kingdom, from fish to people.

“We discovered this mechanism that’s really fundamental across all vertebrates as far as we can tell,” said co-author Andrea Pauli at the Research Institute of Molecular Pathology in Vienna.

The team found that three proteins on the sperm join to form a sort of key that unlocks the egg, allowing the sperm to attach. Their findings, drawn from studies in zebrafish, mice, and human cells, show how this process has persisted over millions of years of evolution. Results were published Thursday in the journal Cell.

Scientists had previously known about two proteins, one on the surface of the sperm and another on the egg’s membrane. Working with international collaborators, Pauli’s lab used Google DeepMind’s artificial intelligence tool AlphaFold — whose developers were awarded a Nobel Prize earlier this month — to help them identify a new protein that allows the first molecular connection between sperm and egg. They also demonstrated how it functions in living things.

It wasn’t previously known how the proteins “worked together as a team in order to allow sperm and egg to recognize each other,” Pauli said.

Scientists still don’t know how the sperm actually gets inside the egg after it attaches and hope to delve into that next.

Eventually, Pauli said, such work could help other scientists understand infertility better or develop new birth control methods.

The work provides targets for the development of male contraceptives in particular, said David Greenstein, a genetics and cell biology expert at the University of Minnesota who was not involved in the study.

The latest study “also underscores the importance of this year’s Nobel Prize in chemistry,” he said in an email.

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The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institute’s Science and Educational Media Group. The AP is solely responsible for all content.

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