It’s possible that I shall make an ass of myself. But in that case one can always get out of it with a little dialectic. I have, of course, so worded my proposition as to be right either way (K.Marx, Letter to F.Engels on the Indian Mutiny)
Saturday, November 05, 2022
Antibiotic resistance linked to these household products: University of Toronto
Holly Barrett, a PhD candidate in the department of chemistry, led a study that found that triclosan, found in many common household products, is the predominant antibiotic in Ontario's sewage sludge.
Credit: Dan Haves
The study, by Assistant Professor Hui Peng’s research group in the department of chemistry in the Faculty of Arts & Science, was able to show that triclosan – a chemical often included in household items like hand soaps, toothpastes, and cleaning products to fight off bacteria – is the predominant antibiotic in Ontario sewage sludge.
“Since there are so many different antibiotics in the sewage sludge, we were surprised to find that the majority of antibacterial activity of the sludge could be directly linked to triclosan alone,” says Holly Barrett, a PhD candidate in the Peng group and lead author on the study.
The research was performed by investigating sewage sludge from Ontario’s sewage treatment plants (STPs). As the study notes, STPs are a breeding ground for antibiotic resistant bacteria due to the diverse set of antibiotics that are found there. That’s because after we rinse our household products down the drain, the antibiotic ingredients in those products are transported to STPs where they accumulate.
Among thousands of co-occurring chemicals in the sludge, triclosan was found to be the predominant antibacterial compound impacting E. coli.
Barrett notes in the study that antibiotic resistance is a growing concern. Antibiotic-resistant bacteria – also commonly known as “superbugs” – are strains of bacteria that are not killed by antibiotics. They are produced when continuous exposure to antibiotics causes bacteria to evolve over several generations to survive antibiotic effects. These bacteria can be very dangerous to humans, especially those with impaired immune systems. Between 2014 and 2016, there were 700,000 deaths around the world attributed to antibiotic resistance.
“I think our results demonstrate that there is an urgent need for regulatory agencies in Canada to re-evaluate the use of triclosan,” says Barrett.
“It’s still used in thousands of different household and cosmetic products in Canada, as well as in health-care settings. While there are a few regulations in place to restrict the maximum amount of triclosan allowed in consumer products, even very low levels of this chemical may cause antibiotic resistant bacteria to form over time.
“More action needs to be taken.”
Self-folding origami honeycombs pave the way to sustainable protective packaging
Scientists develop a low-cost method to make paper sheets fold themselves into honeycomb structures with superb structural and mechanical properties
IMAGE: IN A RECENTLY PUBLISHED STUDY, RESEARCHERS FROM SIT, JAPAN, DEVELOPED A COST-EFFECTIVE METHOD OF MAKING PAPER SHEETS THAT FOLD THEMSELVES WITHOUT ANY HUMAN INTERVENTION INTO HONEYCOMB STRUCTURES WITH SUPERB STRUCTURAL AND MECHANICAL PROPERTIES.view more
CREDIT: HIROKI SHIGEMUNE FROM SIT, JAPAN
Origami, the act of folding flat sheets of material into complex 3D shapes, has transcended its original artistic and ceremonial roots and entered the realm of engineering. Thanks to their low cost and simple fabrication process, origami-based structures and materials have found applications across varied fields, including biomedicine, packaging, spacecrafts, and agriculture.
One of the most difficult aspects of using origami in practical applications is finding a convenient, cost-effective way to fold the sheets of material into the desired shape. The folding process can be particularly challenging for origami structures of either very small or very large size. Accordingly, scientists have been actively trying to come up with new ways to create self-folding origami structures that are compatible with their target application.
In a recent study, a research team from Shibaura Institute of Technology (SIT), Japan, demonstrated a promising method to easily manufacture self-folding origami honeycomb structures (SHSs). As explained in their paper published in Materials & Design, honeycomb structures make for great protective packaging materials owing to their many attractive properties, including low weight, high porosity, heat insulation, and excellent mechanical shock absorption. Motivated by this, the team developed a low-cost process to produce SHSs using nothing but a paper cutter and a standard inkjet printer. The study was led by Associate Professor Hiroki Shigemune and co-authored by Professor Naoki Hosoya and master’s student Daichi Naritomi, all from SIT, as well as Professor Shingo Maeda from Tokyo Institute of Technology. The paper was made available online on September 16, 2022, and will be published in Volume 223 of the journal in November 2022.
The key to this novel method to produce SHSs is to take advantage of the physicochemical interactions that occur between the paper and the printed solution. The researchers first cut out a grid of rectangles on a flat paper sheet and then use the inkjet printer to apply the printing solution in a carefully devised pattern; this results in the honeycomb structures folding themselves in a matter of minutes.
The team focused on analyzing how various parameters of the cutting and printing patterns affected the structural and mechanical properties of the final product. After finding a set of optimal parameters, they tested two additional ways to further improve the mechanical performance of the SHSs. The first was stacking multiple honeycomb layers on top of each other, which greatly increased the cushioning performance of the final structure with negligible changes to its height. The second was pre-straining the honeycomb structure, which is essentially applying a strong compressive force once before the material is put to use. By ‘breaking in’ the material in this way, they eliminate a compressive force peak that occurs the first time a brand new SHSs is compressed, which could damage the protected object.
The proposed approach to create SHSs could see use across a vast range of applications, as Associate Professor Shigemune explains via a few examples: “Our technique could be used to create tailor-made cushioning materials at farm sites based on the type and harvesting period of fruits and vegetables. Alternatively, it could be used to produce evacuation equipment, such as helmets and beds, using SHSs as a core material.”
Another notable advantage of SHSs is that they are made purely out of paper, a material that takes little space to store and that can be processed quickly at low cost. It’s also worth noting that SHSs should be considered green technology since they are made from nontoxic materials using very little energy. “Our technology contributes to sustainable development goals because it allows us to protect fragile components and vegetables, which translates to fewer losses,” remarks Associate Professor Shigemune.
Make sure to be on the lookout for more self-folding origami-based materials and their innovative applications!
As a low-cost option for packaging that is easy to mass produce and configure, self-folding origami structures represent a promising approach to protect fragile goods, such as agricultural produce or electronic equipment.
About Shibaura Institute of Technology (SIT), Japan
Shibaura Institute of Technology (SIT) is a private university with campuses in Tokyo and Saitama. Since the establishment of its predecessor, Tokyo Higher School of Industry and Commerce, in 1927, it has maintained “learning through practice” as its philosophy in the education of engineers. SIT was the only private science and engineering university selected for the Top Global University Project sponsored by the Ministry of Education, Culture, Sports, Science and Technology and will receive support from the ministry for 10 years starting from the 2014 academic year. Its motto, “Nurturing engineers who learn from society and contribute to society,” reflects its mission of fostering scientists and engineers who can contribute to the sustainable growth of the world by exposing their over 8,000 students to culturally diverse environments, where they learn to cope, collaborate, and relate with fellow students from around the world.
About Associate Professor Hiroki Shigemune from SIT, Japan
Associate Professor Hiroki Shigemune graduated from the Dept. of Applied Physics at Waseda University in 2014. He then obtained a master's degree and a PhD from Waseda University in 2016 and 2018, respectively. He joined SIT in 2019, where he works as an Associate Professor of the Department of Electrical Engineering and leads the Shigemune lab. He has published over 40 refereed papers. His main research interests are manufacturing technologies, smart materials, and soft robotics.
Funding Information
This study was supported by JSPS KAKENHI (grant numbers 18H05895 and 19 K20377) and the Adaptable and Seamless Technology Transfer Program through Target-driven R&D (A- STEP) from the Japan Science and Technology Agency (JST) (grant number JPMJTM20CK).
Creation of origami-inspired honeycomb structure using self-folding paper
ARTICLE PUBLICATION DATE
1-Nov-2022
COI STATEMENT
The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Naoki Hosoya, Genki Ando, Shingo Maeda, and Hiroki Shigemune have a patent pending to Naoki Hosoya, Genki Ando, Shingo Maeda, Hiroki Shigemune.
Photos suggest rhino horns have shrunk over past century, likely due to hunting
IMAGE: THEODORE ROOSEVELT STANDS ABOVE A BLACK RHINO HE HAS JUST KILLED (1911).view more
CREDIT: NONE NEEDED
By scrutinising over a century’s worth of photos, University of Cambridge researchers have made the first ever measurements that show rhinoceros horns have gradually decreased in size over time.
The researchers measured the horns of 80 rhinos, photographed in profile view between 1886 and 2018. The photographs, held by the Rhino Resource Centre - an online repository - included all five species of rhino: white, black, Indian, Javan and Sumatran. Horn length was found to have decreased significantly in all species over the last century.
Real rhino horns are so valuable that strict security protocols typically prevent researchers accessing them for study, so this is the first time that horn length has been measured over a long timeframe.
The researchers think rhino horns have become smaller over time due to intensive hunting. Rhino horns command a high price and are in demand both as a financial investment, and for their use in traditional medicines in China and Vietnam.
Hunting has not only caused severe declines in rhino populations; the researchers suggest that shooting rhinos with the longest horns has increasingly left smaller-horned survivors – which have reproduced more and passed on their smaller traits to future generations. This has been shown for other animals before, but never rhinos.
“We were really excited that we could find evidence from photographs that rhino horns have become shorter over time. They’re probably one of the hardest things to work on in natural history because of the security concerns,” said Oscar Wilson, formerly a researcher in the University of Cambridge’s Department of Zoology, first author of the report. Wilson is now based at the University of Helsinki, Finland.
He added: “Rhinos evolved their horns for a reason - different species use them in different ways such as helping to grasp food or to defend against predators - so we think that having smaller horns will be detrimental to their survival.”
The researchers also measured other body parts on each rhino photograph, including body and head length, so that horn length could be accurately measured in proportion to body size.
By analysing thousands of drawings and photographs made over the last 500 years, the researchers also saw a dramatic shift in human perceptions of rhinos around 1950, when the animals became the focus of conservation efforts rather than hunting.
“We found that we can use images from the last few centuries to visualise how human attitudes towards wildlife have changed, and how artists have influenced these views,” said Dr Ed Turner at the University’s Department of Zoology, senior author of the report.
Many hundreds of photographs showing rhinos shot dead by hunters, taken in the late 19th and early 20th century, are included in the collection. These include a photograph of American President Theodore Roosevelt, taken in 1911, standing triumphantly over a black rhino he had just killed.
Other early images show rhinos as huge, frightening animals chasing humans. The researchers think these images helped justify the hunting of these animals.
The images suggest that there was very little effort to promote rhino conservation to the public before the 1950s. But after this the focus suddenly changed from hunting the animals to trying to keep them alive. The researchers say this shift coincides with the collapse of European empires, when African countries became independent and European hunters no longer had easy access to Africa for hunting.
More recent images appear to reflect a growing awareness of the threats facing the natural world.
“For at least a few decades now there’s been much more of a focus on the conservation of rhinos – and this is reflected in the more recent images, which relate to their conservation in sanctuaries or their plight in the wild,” said Wilson.
The Rhino Resource Centre holds over 5000 illustrations and photographs of rhinos, drawn together from extensive archival research and submissions from rhino experts. Artwork covers over 500 years, and photographs cover the past 150 years.
Sumatran rhino in 1986 (IMAGE)
Rhino in a UK safari park.
CREDIT
Kees Rookmaaker
Indian rhinos in 2021 (IMAGE)
Indian rhinos (a mother and her calf) at Whipsnade Zoo, UK
AGENCY FOR SCIENCE, TECHNOLOGY AND RESEARCH (A*STAR), SINGAPORE
IMAGE: RESEARCHERS WITH THE PAPILIONANTHE MISS JOAQUIM. (FROM LEFT TO RIGHT) PROF TEH BIN TEAN, DIRECTOR, SINGHEALTH DUKE-NUS INSTITUTE OF BIODIVERSITY MEDICINE, AND SENIOR GROUP LEADER OF THE LABORATORY OF BIODIVERSITY GENOMICS AT GIS, AND PROF PATRICK TAN, EXECUTIVE DIRECTOR OF THE GENOME INSTITUTE OF SINGAPORE. PHOTO CREDIT: SINGHEALTHview more
CREDIT: SINGHEALTH
A collaboration between A*STAR’s Genome Institute of Singapore (GIS) and SingHealth Duke-NUS Institute of Biodiversity Medicine (BD-MED) has decoded the entire genetic blueprint of Singapore’s National Flower, Papilionanthe Miss Joaquim, also commonly known as Vanda Miss Joaquim (VMJ). Chemical profiling, informed by the genome analysis, further uncovered natural products such as flavonols and anthocyanins, notable for their antioxidant properties and distinctive colour pattern. The study was published in Communications Biology on 15 September 2022.
VMJ was declared the National Flower of Singapore in 1981, and has since captured the fascination of both locals and tourists. The GIS and BD-MED teams employed various genetic sequencing technologies to assemble the entire VMJ genome for the first time, revealing a total of 19 chromosomes spanning 2.4 billion nucleic acid base pairs with approximately 32,000 genes. These genes influence the production of proteins which impact the orchid’s traits and cellular processes, and demonstrated the presence of natural products in our national flower responsible for its distinctive colour pigmentation, smell, and other natural bioactive compounds.
Knowledge of the VMJ genome enables the team to perform chemical profiling to uncover VMJ’s antioxidant properties and distinctive colour pattern—flavonols and anthocyanins. The orchid was also found to contain vandaterosides, a bioactive compound capable of slowing the skin-ageing process which was previously discovered in Papilionanthe Teres, the seed parent of VMJ.
Prof Teh Bin Tean, Director of SingHealth Duke-NUS BD-MED, and Senior Group Leader of the Laboratory of Biodiversity Genomics at A*STAR's GIS, said, “We are heartened to be able to construct and decipher the genetic blueprint of our national flower, and hope that this achievement will be a significant contribution to our national heritage. VMJ is an orchid hybrid with magnificent blooms, and it is widely used as a breeding stalk for over 400 various orchid hybrids. Findings on its genomic makeup could help us better understand how to enhance genomic resources and pave the way for future research in gene and metabolite engineering. Deciphering the genetic code of flora species such as the VMJ also allows us to uncover naturally occurring bioactive compounds, which could be used for healthcare purposes and to understand, prevent and fight diseases.”
Prof Patrick Tan, Executive Director of GIS, said, “Singapore’s biodiversity is well represented, with over 4,000 species of native flora which are threatened in the face of global climate irregularities and issues. Thanks to advancing sequencing technology, we are able to conserve the genomes of flora by preserving the genetic code through sequencing. We are tremendously honoured to start our journey studying Singapore’s plant biodiversity with our national flower.”
JOURNAL
Communications Biology
ARTICLE TITLE
Genome assembly and chemogenomic profiling of National Flower of Singapore Papilionanthe Miss Joaquim ‘Agnes’ reveals metabolic pathways regulating floral traits
The WHAM Report: Investing just $40 million new dollars in lung cancer research related to women has dramatic impact on U.S. economy – even assuming the most minor health improvements
Greenwich, CT (November 1, 2022)—Doubling the funding for research focused on women and lung cancer will have enormous economic impacts for families and the nation, according to a new report released today by Women’s Health Access Matters (WHAM), which commissioned The RAND Corporation to create this study on lung cancer in women. According to rigorous modeling based on a number of conservative estimates, even health improvements of 0.1 percent in mortality and quality of life will yield a return on investment of $1,200 for every additional dollar spent. Today’s findings mirror three previous studies from WHAM, which were executed by The RAND Corporation and show similar findings with respect to the power of investment for women’s health research associated with Alzheimer’s disease, heart disease and rheumatoid arthritis.
For lung cancer, this is particularly critical because in the U.S., lung cancer is the number one cause of cancer death in women. More women die of lung cancer (estimated approximately 61,000 in 2022, according to CA: A Cancer Journal for Clinicians) than of breast, ovarian and cervical cancers combined. And non-smoking women are more than two times as likely to get lung cancer as their male counterparts, yet the sex disparities of the disease have yet to be thoroughly examined, and only 15 percent of lung cancer research is focused on women.
Lung cancer research receives the least amount of funding of the major cancers affecting women. The new report is a first-of-its-kind microsimulation model that examines socioeconomic impacts of investments in women’s health research in the U.S. – revealing critical gaps in the nation’s current research portfolio and the potential gain to the economy through greater funding.
The new research examines the return on investment if the research funding for women and lung cancer were doubled. Assuming that the additional research generates health improvements of only 0.1 percent or less in terms of age incidence, mortality and quality of life, the nation can reliably anticipate the following payoff:
For the U.S. population aged 25 and older, more than 22,700 years can be saved across 30 years of extended life, with substantial gains in health-related quality of life.
Approximately 2,500 more labor years (valued at $45 million in labor productivity) result from increased work time and longer life.
Overall, doubling the investment would have an expected ROI of more than 1,200 percent.
“These findings are stunning,” said WHAM Founder and CEO Carolee Lee. “Women are sick and dying from a disease that disproportionately affects them, yet research doesn’t acknowledge this fact. And the pain of disease is not just a medical problem by any means. This new data could not be more clear about the economic pain we all pay when women leave the workforce early to manage their own health or serve as caregivers for their loved ones. Women’s health is an economic issue that impacts everyone, and we can’t afford to ignore it.”
“This research shows that very small investments in women’s health can generate outsized returns, in part because women’s health research is still very much under-funded,” said Lori Frank, senior author of the study. “Our modeling suggests that even small investments in women’s lung cancer research could result in significant gains in health outcomes, health-related quality of life and workforce productivity. But it also points to the importance of addressing diseases that hit women harder; equity in medical research leads to meaningful benefits.”
“This report brings important new data to the case that we have been making for years: that lung cancer impacts women differently – both physically and societally – and these disparities must be addressed,” said Laurie Fenton Ambrose, President and CEO of GO2 for Lung Cancer and supporter of the report. “The WHAM findings not only underscore the need for legislation that expands resources to better understand the science of lung cancer in women, but also show how investing in research could result in economic benefits for women living with the disease.”
The WHAM Report can be a tool to help decisionmakers plan for future research strategies, help funders decide how to allocate their portfolios, and address the business case for payers and business leaders to invest in women’s health.
The report authors recommend expanding the research agenda to address multiple aspects of sex and gender in lung cancer using the limited evidence base, including:
The unknown interactions of sex and gender with lung cancer etiology, risk factors and disease progression to inform treatment and prevention research.
Understudied interactions of gender and race with lung cancer risk, health care and disease progression; in particular, examining obstacles to access to and use of diagnostic technology, including for personalized medicine.
Differences by sex and gender in lifestyle impacts on disease.
Differences in disease course and outcomes by sex and gender, based on different patterns of the use of formal and informal caregiving.
“Women are more than half of the population and workforce, control 60 percent of personal wealth, and are responsible for 85 percent of consumer spending and 80 percent of healthcare decisions,” said Lee. “Yet even while diseases impact them disproportionately and differently, pulling many from the workforce too soon, investment in women’s health research lags. This is such an easy win for our country.”
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WHAM (Women’s Health Access Matters, whamnow.org) Women’s health is an economic issue we can’t afford to ignore. WHAM works to increase awareness of and funding for women’s health research by accelerating scientific discovery in women’s health in four primary disease verticals – autoimmune disease, brain health, cancer, and heart health. The WHAM Report quantifies the economic opportunity for investing in women’s health, looking across diseases that impact women differently and differentially, including coronary artery disease, rheumatoid arthritis, and Alzheimer’s disease. Learn more at www.thewhamreport.org.
The RAND Corporation is a research organization that develops solutions to public policy challenges to help make communities throughout the world safer and more secure, healthier and more prosperous. Learn more at www.rand.org.
GO2 for Lung Cancer is leading the charge to confront lung cancer – and we're taking it on relentlessly from every front, every day. Founded by patients and survivors, we’re the go-to for one-on-one assistance, supportive connections, treatment information, and finding the best care in our local communities. We’re the place to go to learn about the latest research and special initiatives that increase survivorship – especially for our most vulnerable and underserved. We’re the source for improving health policies and leading public awareness to shift this disease from one of stigma to one of hope. Learn more at www.go2.org.
Calls for five year old students to learn how to protect themselves online
A new report has recommended early childhood school curriculums need to include cybersecurity education to protect children online.
IMAGE: CYBERSECURITY EXPERTS SAY CHILDREN AS YOUNG AS FIVE NEED BE TO BE TAUGHT HOW TO PROTECT THEMSELVES ONLINE.view more
CREDIT: PIXABAY
More children than ever are using the internet, and they’re using it younger than ever before.
Now, a new report led by Edith Cowan University (ECU) Associate Professor and Security Research Institute (SRI) Deputy Co-Director Dr Nicola Johnson has recommended additional consultation around cybersecurity curriculum needs to occur.
“We need to start early with five-year-olds. We need to get the curriculum ‘right’ for Western Australia. There is a need to educate people from a young age to protect themselves from common cybersecurity threats,” Dr Johnson said.
Cybersecurity curriculum mapping
The Cyber Security Cooperative Research Centre 2022 report determined that WA school children might miss out on learning key cybersecurity skills in the current curriculum.
“Exactly what needs to be taught surrounding cybersecurity needs to be very clear within the curriculum. Teachers need professional learning to help them teach cybersecure behaviour effectively and confidently.
While primary students are taught about the dangers of using the internet and how to be safe online, the report pointed to the vagueness of what is to be covered in the new version of the Australian Curriculum.
“It is only in year 11 and 12 elective subjects that students are taught what is now fundamental aspects of cybersecurity; this is too late,” Dr Johnson explained.
In year 11, students completing Computer Science as a part of their WA ATAR are required to learn the role of ethical hacking in network security, penetration testing, encryption, and two-factor authentication.
“There is a strong case for this key knowledge as well as Australian privacy principles and laws to be explicitly taught at much younger ages, given how cyber criminals so quickly and creatively come up with new ways to scam our citizens.”
Securing the future of cybersecurity
Australia is experiencing a critical shortfall in the cybersecurity workforce.
Recognised by the Federal Government as the fastest growing employment sector with an estimated 17,000 new jobs by 2026, Dr Johnson says more intensive cyber security teaching in schools could ease future shortages.
“By teaching content typically learned in senior secondary to younger children, we can reduce both future job shortages and the enormous cost of cybercrime,” Dr Johnson said.
“We acknowledge that for these changes to be implemented, attention needs to be given to resourcing, particularly in regional schools. This can be achieved by further consultation with industry providers and the Australian Cyber Security Centre (ACSC).”
Dr Johnson is co-facilitating stakeholder consultation workshops at the end of November. Interested participants should make contact.
The report was compiled with research from Edith Cowan University staff including Dr Nicola Johnson, Deputy Co-Director of the Security Research Institute (SRI), Associate Professor of Digital Technologies in Education, School of Education, Dr Leslie Sikos, SRI/School of Science, Dr Ahmed Ibrahim, SRI/School of Science, and Dr Cheryl Glowrey, School of Education.
The project is supported by the Government of Western Australia, the Office of Digital Government (DGov), under its participation in Cyber Security Cooperative Research Centre (CSCRC). ECU and SRI performs research and development as the CSCRC’s research provider.
The work has been supported by the Cyber Security Research Centre Limited whose activities are partially funded by the Australian Government’s Cooperative Research Centres Programme.
METHOD OF RESEARCH
Observational study
SUBJECT OF RESEARCH
People
Monoclonal antibody prevents malaria infection in African adults
Antibody protected NIH clinical trial participants during six-month malaria season
NIH/NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
IMAGE: AN ANTIBODY DRUG CALLED CIS43LS PREVENTS MALARIA INFECTION BY INTERRUPTING THE LIFECYCLE OF THE PLASMODIUM FALCIPARUM PARASITE. THE ANTIBODY BINDS TO AND NEUTRALIZES SPOROZOITES, THE STAGE OF THE PARASITE TRANSMITTED FROM MOSQUITOS TO HUMANS.view more
CREDIT: NIH
One dose of an antibody drug safely protected healthy, non-pregnant adults from malaria infection during an intense six-month malaria season in Mali, Africa, a National Institutes of Health clinical trial has found. The antibody was up to 88.2% effective at preventing infection over a 24-week period, demonstrating for the first time that a monoclonal antibody can prevent malaria infection in an endemic region. These findings were published today in The New England Journal of Medicine and presented at the American Society of Tropical Medicine & Hygiene 2022 Annual Meeting in Seattle.
“We need to expand the arsenal of available interventions to prevent malaria infection and accelerate efforts to eliminate the disease,” said Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID), part of NIH. “These study results suggest that a monoclonal antibody could potentially complement other measures to protect travelers and vulnerable groups such as infants, children, and pregnant women from seasonal malaria and help eliminate malaria from defined geographical areas.”
NIAID sponsored and funded the trial, which was led by Peter D. Crompton, M.D., M.P.H., and Kassoum Kayentao, M.D., M.P.H., Ph.D. Dr. Crompton is chief of the Malaria Infection Biology and Immunity Section in the NIAID Laboratory of Immunogenetics, and Dr. Kayentao is a professor at the University of Sciences, Techniques and Technologies (USTTB) of Bamako, Mali.
An estimated 241 million cases of malaria occurred worldwide in 2020, according to the World Health Organization (WHO), resulting in an estimated 627,000 deaths, mostly in children in sub-Saharan Africa. These cases included more than 11 million pregnant women in Africa, resulting in an estimated 819,000 newborns with low birthweight and thus at increased risk for illness and death.
The only malaria vaccine currently recommended by WHO, called RTS,S (Mosquirix), provides partial protection against clinical malaria during the early years of life when given to children aged 5 to 17 months in four doses over a 20-month period. Other drugs consisting of small chemical compounds that effectively prevent malaria infection are also available for infants and young children as well as travelers. The requirement for frequent dosing of these drugs can limit adherence, however, and the emergence of drug resistance may also limit their usefulness. Thus, there is an urgent need for new, fast-acting, infrequently dosed interventions that safely provide strong protection against malaria infection.
Malaria is caused by Plasmodium parasites, which are transmitted to people through the bite of an infected mosquito. The mosquito injects the parasites in a form called sporozoites into the skin and bloodstream. These travel to the liver, where they mature and multiply. Then the mature parasite spreads throughout the body via the bloodstream to cause illness. P. falciparum is the Plasmodium species most likely to result in severe malaria infections, which, if not promptly treated, may lead to death.
The Phase 2 NIAID-USTTB trial evaluated the safety and efficacy of a one-time, intravenous infusion of a monoclonal antibody called CIS43LS. This antibody was previously shown to neutralize the sporozoites of P. falciparum in the skin and blood before they could infect liver cells. Researchers led by Robert A. Seder, M.D., isolated a naturally occurring form of this antibody from the blood of a volunteer who had received an investigational malaria vaccine, and then modified the antibody to extend the length of time it would remain in the bloodstream. Dr. Seder is the acting chief medical officer and acting associate director of the NIAID Vaccine Research Center (VRC) and chief of the VRC’s Cellular Immunology Section.
The study team for the Phase 2 trial enrolled 369 healthy, non-pregnant adults aged 18 to 55 years in the rural communities of Kalifabougou and Torodo in Mali, where intense P. falciparum transmission typically occurs from July through December each year.
The first part of the trial assessed the safety of three different doses of CIS43LS—5 milligrams per kilogram of body weight, 10 mg/kg and 40 mg/kg—administered by intravenous infusion in 18 study participants, with six participants per dose level. The study team followed these participants for 24 weeks and found the antibody infusions were safe and well-tolerated.
The second part of the trial assessed the efficacy of two different doses of CIS43LS compared to a placebo. Three hundred and thirty participants were assigned at random to receive either 10 mg/kg of the antibody, 40 mg/kg, or a placebo by intravenous infusion. No one knew who was assigned to which group until the end of the trial. The study team followed these individuals for 24 weeks, testing their blood for P. falciparum weekly for the first 28 days and every two weeks thereafter. Any participant who developed symptomatic malaria during the trial received standard treatment from the study team.
The investigators analyzed the efficacy of CIS43LS two ways. Based on the time to first P. falciparum infection over the 24-week study period, the high dose (40 mg/kg) of CIS43LS was 88.2% effective at preventing infection and the lower dose (10 mg/kg) was 75% effective. An analysis of the proportion of participants infected with P. falciparum at any time over the 24-week study period found the high dose was 76.7% at preventing infection and the lower dose was 54.2% effective.
“These first field results demonstrating that a monoclonal antibody safely provides high-level protection against intense malaria transmission in healthy adults pave the way for further studies to determine if such an intervention can prevent malaria infection in infants, children, and pregnant women,” Dr. Seder said. “We hope monoclonal antibodies will transform malaria prevention in endemic regions.”
Dr. Seder and colleagues have developed a second antimalarial monoclonal antibody, L9LS, that is much more potent than CIS43LS and therefore can be administered in a smaller dose as an injection under the skin (subcutaneously), rather than by intravenous infusion. An early-phase NIAID trial of L9LS in the United States found that the antibody was safe and prevented malaria infection for 21 days in 15 out of 17 healthy adults exposed to P. falciparum in a carefully controlled setting. Two larger, NIAID-sponsored Phase 2 trials assessing the safety and efficacy of L9LS in infants, children and adults are underway in Mali and Kenya.
Additional information about the Phase 2 trial of CIS43LS is available at ClinicalTrials.gov under study identifier NCT04329104.
K Kayentao et al. Safety and efficacy of a monoclonal antibody against malaria in Mali. The New England Journal of Medicine DOI: 10.1056/NEJMoa2206966 (2022).
RL Wu et al. Low-dose subcutaneous or intravenous monoclonal antibody to prevent malaria. The New England Journal of Medicine DOI: 10.1056/NEJMoa2203067 (2022).
NIAID conducts and supports research—at NIH, throughout the United States, and worldwide—to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website.
About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit https://www.nih.gov/.
