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.
Canada considering smallpox vaccine for monkeypox cases, says Dr. Theresa Tam
OTTAWA — The risk posed by monkeypox is low, but nearly everyone in Canada is susceptible because routine vaccination against smallpox ended decades ago, top public health officials said Friday.
Monkeypox is a rare disease that comes from the same family of viruses as variola. That virus causes smallpox, which the World Health Organization declared eradicated around the globe in 1980. It is also linked to the vaccinia virus used in the smallpox vaccine.
The Public Health Agency of Canada, which is investigating about two dozen possible cases of monkeypox on top of two confirmed cases in Quebec, says it is spread through prolonged close contact. That includes through direct contact with an infected person’s respiratory droplets, bodily fluids or sores, and is not very contagious in a typical social setting.
The B.C. Centre for Disease Control said Friday that it is not investigating any suspected cases or possible contacts of monkeypox in the province after having ruled out two potential contacts.
Canada’s chief public health officer Dr. Theresa Tam said the federal public health agency does not know how widespread the disease has become in the country.
Monkeypox is typically milder than smallpox and can cause fever, headache, muscle aches, exhaustion, swollen lymph nodes and lesions all over the body.
There is global evidence that smallpox vaccines can offer protection against monkeypox.
But Canada stopped routinely immunizing people against smallpox in 1972.
Tam’s deputy, Dr. Howard Njoo, said this means everyone is susceptible to monkeypox.
“I would say, generally, the entire population is susceptible to monkeypox,” Njoo said Friday.
Canada does keep a small stockpile of smallpox vaccine in case of a biological incident, like a laboratory exposure.
A smattering of cases in the United Kingdom prompted that country to begin offering the vaccine to health workers and close contacts of confirmed cases.
Tam said Canada is considering a similar strategy.
“Quebec had some interest in terms of the contacts so that is under discussion right now, but of course we need to know some of the epidemiology as quickly as possible,” Tam said.
She would not say how many doses of the smallpox vaccine Canada has available, citing security reasons.
Public Services and Procurement Canada put out a tender last month to purchase 500,000 doses of the Imvamune smallpox vaccine on behalf of the Public Health Agency of Canada from 2023 to 2028.
“Although smallpox disease is currently considered to be eradicated, PHAC is procuring a stockpile of the vaccine to immunize Canadians against smallpox disease should a risk ever arise where smallpox is intentionally or unintentionally released,” the tender read.
Health Canada has also approved that vaccine, from Danish biotech company Bavarian Nordic, for use to prevent monkeypox.
The company announced Thursday it had secured a deal with an unnamed European country to supply its vaccine in response to monkeypox cases.
There is still a sense of mystery surrounding the sudden appearance of the virus in Canada, the U.S., Australia and several parts of Europe.
“Not many of these individuals are connected to travel to Africa where the disease is normally seen, so this is unusual. It’s unusual for the world to see this many cases reported in different countries outside of Africa,” Tam said.
Canadian health systems are casting a wide net in their search for more cases, she said, because there is not enough known about why the virus is suddenly cropping up around the globe.
“There’s probably been some hidden chains of transmission that could have occurred for quite a number of weeks, given the sort of global situation that we’re seeing right now,” she said.
Njoo said global public health authorities need to be open to the idea that monkeypox is evolving, and transmission may have changed as well.
For now, samples from suspected cases are being sent to the National Microbiology Laboratory in Winnipeg, but PHAC is working with provinces to set up more local diagnostics.
This report by The Canadian Press was first published May 20, 2022.
Laura Osman, The Canadian Press
Persisting coronavirus could drag out COVID-19 symptoms – National Geographic
Most COVID-19 patients recover from their acute infection within two weeks, but bits of the virus don’t always disappear from patients’ bodies immediately. Now a new study, one of the largest focusing on hospitalized COVID-19 patients, shows that some patients harbor these viral remnants for weeks to months after their primary COVID-19 symptoms resolve.
The study suggests that when the genetic material of the virus, called RNA, lingers in the body longer than 14 days, patients may face worse disease outcomes, experience delirium, stay longer in the hospital, and have a higher risk of dying from COVID-19 compared with those who cleared the virus rapidly. The persistence of the virus may also play a role in long COVID, the debilitating suite of symptoms that can last for months. Estimates suggest between 7.7 and 23 million people in the United States alone are now affected by long COVID.
Without immunity from vaccination or a previous infection, SARS-CoV-2—the virus that causes COVID-19—replicates and spreads throughout the body and is shed through the nose, mouth, and gut. But for most infected people, virus levels in the body peak between three and six days after the original infection, and the immune system clears the pathogen within 10 days. The virus shed after this period is generally not infectious.
Even after accounting for disease severity, whether the patients were intubated, or had underlying medical comorbidities, “there is something here that signals that patients who are persistently PCR positive have worse outcomes,” says Ayush Batra, a neurologist at Northwestern University Feinberg School of Medicine, who led the new study.
Batra’s study shows that patients who had prolonged shedding during an acute infection risk more severe outcomes from COVID-19, says Timothy Henrich, a virologist and immunologist at the University of California, San Francisco who was not involved in the new research. But the study doesn’t investigate whether this persistent virus is directly responsible for long COVID.
“There are multiple leading hypotheses out there about the cause of long COVID, including viral persistence, and it may be that there are multiple pathways at play, perhaps to some varying degree in any one person,” says Linda Geng, a doctor at Stanford Health Care who co-directs a newly opened Post-Acute COVID-19 Syndrome Clinic for treating long COVID sufferers.
Persisting virus causes worse COVID-19 outcomes
Batra and his team began studying persistent coronavirus infections after observing that some patients who were returning to the hospital were still testing positive for the virus four or five weeks after they were diagnosed with the initial infection.
For their new study, the team analyzed 2,518 COVID-19 patients hospitalized in the Northwestern Medicine Healthcare system between March and August 2020. They focused on PCR tests, which are considered the gold standard, because such tests detect genetic material from the virus and so are highly sensitive and less likely to return false negatives.
The team found that 42 percent of patients continued to test PCR positive two weeks or longer after their initial diagnosis. After more than 90 days, 12 percent of the persistent shedders were still testing positive; one person tested positive 269 days after the original infection.
Viral persistence has been noted before in previous smaller studies. Researchers showed that even patients without obvious COVID-19 symptoms harbored SARS-CoV-2 for a couple of months and beyond. In some immunocompromised patients, the virus may not be cleared for a year. Four percent of COVID-19 patients in a trial on chronic COVID-19 infection at Stanford continued to shed viral RNA in feces seven months after diagnosis. However, Batra’s study illustrates that a larger number of patients take longer to clear the virus than previously realized.
“Persistent RNA shedding would mean that there still is a reservoir of virus somewhere in the body,” says Michael VanElzakker, a neuroscientist affiliated with Massachusetts General Hospital, Harvard Medical School and Tufts University. Such reservoirs are thought to allow the virus to persist over a long period of time and could trigger the immune system to act aberrantly, perhaps causing long COVID.
“Some patients, for variety of reasons, are not able to clear this reservoir, or their immune system reacts in some abnormal way that results in these persistent symptoms that have come to be termed as long COVID,” says Batra.
Still, many scientists don’t think there is sufficient evidence yet to link the persistence of viral RNA to long COVID.
The list of human tissues where SARS-CoV-2 hides long after the initial infection is growing. Studies have identified the virus, or genetic material from it, in the intestines of patients four months after initial infection, and inside the lung of a deceased donor more than a hundred days after recovery from COVID-19. One study that’s not yet peer reviewed also detected the virus in the appendix and breast tissues 175 and 462 days, respectively, after coronavirus infections. And research from the U.S. National Institutes of Health that’s also not yet peer reviewed detected SARS-CoV-2 RNA persisting at low levels across multiple tissues for more than seven months, even when it was undetectable in blood.
“It is not surprising to find viruses encountered during the lifetime” surviving in human tissues, says Kei Sato, a virologist at the University of Tokyo. Indeed, Sato’s work has shown that humans frequently accumulate viruses such as Epstein-Barr virus, varicella zoster virus (which causes chicken pox), and many herpes viruses in dormant forms. These persisting viruses are typically present at low levels, so only extensive genetic sequencing can identify them.
This highlights how complicated it is to prove or disprove the association between persisting SARS-CoV-2 and long COVID. Shingles, for example, occurs decades after a chickenpox infection, when the latent virus gets reactivated during immune stress.
Likewise, lingering SARS-CoV-2 could cause long-term health problems. Henrich thinks when the virus is seeded in deep tissues, it potentially causes the immune system to shift into a dysregulated inflammatory state. Such a state is “probably evidence that the virus is capable of persisting, and maybe getting down into sort of an uneasy truce with the body,” says VanElzakker.
Still, associating any lingering virus with long COVID will require extensive studies. “We still don’t know enough to make strong conclusions about any of the current proposed mechanisms, but research is actively underway to answer those questions,” says Geng.
Clearing up persistent virus might cure long COVID
Both Geng and Henrich’s groups have reported preliminary case studies that show an improvement in long COVID symptoms after patients were treated with Pfizer’s COVID-19 oral antiviral Paxlovid. Paxlovid stops the virus from replicating, which is why some experts think it can clear any lingering virus. But both authors urge caution before assuming that Paxlovid will be safe, effective, or sufficient and thereby a reliable cure for long COVID.
“There are some interesting hypotheses about how Paxlovid may be useful in the treatment of long COVID, but we’d need further investigation and clinical trials before coming to any conclusions,” says Geng.
The U.S. Food and Drug Administration has warned against off-label uses of Paxlovid, which is not approved for long COVID treatment. The agency has given Paxlovid an emergency use authorization to treat mild to moderate COVID-19 in those who are at risk of developing severe disease, twice daily for five days soon after a positive test.
“It would be important to consider the optimal duration of treatment [of Paxlovid] to ensure long-term and sustained results,” says Geng.
President Joe Biden has directed the secretary of Health and Human Services to create a national action plan on long COVID, and the NIH has launched a multi-year study called RECOVER to understand, prevent, and treat long-term health effects related to COVID-19.
In the meantime, vaccines not only continue to protect against severe disease, but evidence is also emerging that they can prevent many long COVID symptoms. One new study compared 1.5 million unvaccinated COVID-19 patients to 25,225 vaccinated patients with breakthrough infections, and it found that vaccines significantly reduced the risk of developing long COVID symptoms 28 days after an infection. The protective effect of vaccination got even larger at 90 days post-infection.
“Although a majority of people do not develop long COVID, it’s certainly a risk, and COVID doesn’t stop after the first 10 days of becoming infected,” says Henrich. “For those who don’t take COVID seriously, it can be life changing.”
No suspected cases of monkeypox in B.C., CDC says – Global News
The BC Centre for Disease Control has confirmed there are no suspected cases of monkeypox in the province.
“Public health interviewed two individuals but upon investigation, it was determined that they were not considered contacts of cases as they had not been exposed,” the BCCDC said in a statement.
“No suspect cases or contacts of monkeypox are under investigation in B.C. at this time.”
Canada’s chief public health officer said earlier Friday there are now just under two dozen cases of monkeypox in Canada and there were some suspected cases in B.C.
Dr. Theresa Tam said Friday that “people under investigation by local authorities are following up in Quebec but then in British Columbia as well.”
“A communication has gone out to regional health authorities and medical microbiologists about monkeypox with information on symptoms, laboratory testing and diagnosis, infection control precautions, treatment and notification/reporting requirements,” the BCCDC said in a statement. “Clinicians are asked to notify their regional health authority and local microbiologist about any possible cases.”
Canada’s top doctor discusses vaccine strategies for monkeypox
Monkeypox is a zoonotic infectious disease that results in occasional human infections usually associated with exposure to infected animals or contaminated materials, according to the Public Health Agency of Canada (PHAC).
“Limited cases have been identified in other regions in the past, including the United Kingdom, United States, Israel and Singapore, but never before in Canada,” the agency said.
While human-to-human spread of monkeypox is uncommon, close contact with an infected individual through bodily fluids, lesions on skin like blisters and/or respiratory droplets can transmit the virus, PHAC said.
Sharing clothing, bedding or common items that have been contaminated with the infected person’s fluids or sores can also spread the virus.
On Wednesday, the U.S. confirmed its first case of monkeypox this year in a man who recently travelled to Canada.
Health officials in European countries where monkeypox cases have been found this month said the majority of the cases were men who have sex with men.
Monkeypox: What is it and is it a cause for concern?
Tam said Friday there could be more cases announced in the days ahead as tests are still being conducted.
“There are samples under processing at the National Microbiology Lab as we speak, so we might expect to hear more confirmations in the upcoming hours and days,” Tam told reporters during a news conference on Friday.
—with files from Saba Aziz
© 2022 Global News, a division of Corus Entertainment Inc.
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