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Washington, DC (October 23, 2020) -- The results of numerous high-impact clinical trials that could affect kidney-related medical care will be presented online during ASN Kidney Week 2020 Reimagined October 19-October 25.

* Mineralocorticoid receptor overactivation may drive progression of chronic kidney disease through inflammatory and fibrotic processes. In a randomized, phase 3, placebo-controlled trial including 5,734 patients with chronic kidney disease and type 2 diabetes, investigators tested the efficacy and safety of finerenone, a novel mineralocorticoid receptor inhibitor. Compared with placebo, finererone significantly reduced the risk of developing kidney failure or cardiovascular problems, and it was well-tolerated. "The FIDELIO-DKD trial is the first to demonstrate that a novel mineralocorticoid receptor blocker, different from traditional agents in the class, slows diabetic kidney disease progression and reduces cardiovascular events when added to standard of care. Additionally, this added benefit is with minimal risk of elevating serum potassium, a problem commonly seen with other agents in the class," said lead author George L. Bakris, MD, of the University of Chicago Medicine.

Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes

* In an analysis of 3,730 patients with heart failure and a reduced ejection fraction (HFrEF) enrolled in the EMPEROR-Reduced trial, the diabetes medication empagliflozin lowered the risks of heart failure, cardiovascular death, and serious kidney problems; and slowed kidney function decline compared with placebo. These effects were seen regardless of the presence or absence of chronic kidney disease and across a broad spectrum of baseline kidney function.

EMPEROR-Reduced: Empagliflozin and Outcomes in Heart Failure and Chronic Kidney Disease

* A cyclical corticosteroid-cyclophosphamide regimen is recommended for patients with primary membranous nephropathy at high risk of progression. In a randomized and open-label controlled trial, 86 patients with primary membranous nephropathy and persistent nephrotic syndrome were assigned to receive a 6-month cyclical treatment with corticosteroid and cyclophosphamide or sequential treatment with tacrolimus and rituximab. Compared with tacrolimus-rituximab, corticosteroid-cyclophosphamide induced remission of nephrotic syndrome at 24 months in a significantly greater number of patients. "In the STARMEN study, treatment with corticosteroid-cyclophosphamide was more effective (84%) than treatment with tacrolimus and rituximab (55%) in primary membranous nephropathy," stated lead author Gema Fernández Juárez, MD, of Hospital Univesitario Fundacion Alcorcón, in Spain.

Sequential Treatment with Tacrolimus and Rituximab versus alternating Corticosteroids and Cyclophosphamide in Primary Membranous Nephropathy (PMN)

* Vadadustat (VADA) is an investigational, oral, hypoxia-inducible factor prolyl hydroxylase inhibitor being tested for the treatment of anemia in patients with chronic kidney disease. Researchers conducted 2 randomized, phase 3, global, open-label, sponsor-blind, parallel-group, active-controlled trials comparing oral daily VADA to parenteral darbepoetin alfa (DA) in patients with anemia and CKD who are not on dialysis (PRO2TECT program). In total, 1,751 patients were randomized. Results will be presented at the meeting.

Global Phase 3 Clinical Trials of Vadadustat vs Darbepoetin Alfa for Treatment of Anemia in Patients with Non-Dialysis-Dependent Chronic Kidney Disease

* Hemodialysis is an intensive procedure that puts stress on patients who need it to survive. For patients with poor nutrition, eating protein during dialysis appears to improve their survival, but whether oral protein supplements can also help patients with better nutritional status is unknown. The Health Effects of oraL Protein Supplements in HD (HELPS-HD) Trial of 10,043 patients undergoing hemodialysis compared nutritional supplementation only when patients had poor nutritional status, indicated by low blood levels of albumin, the most abundant protein in blood, (the standard protocol), vs. nutritional supplementation regardless of blood albumin levels (the intensive protocol). Mortality rates were similar in the 2 groups: over a median follow-up of 21 months, there were 3,628 deaths, 35.8% in the intensive and 36.5% in the standard group. The rate of death was approximately 20 per 100 people over 1 year in both groups. "The findings suggest that giving protein supplements at dialysis to hemodialysis patients with more normal nutritional status does not lower the risk of death in hemodialysis patients," said lead author Daniel E. Weiner, MD, of Tufts Medical Center.

Oral Intradialytic Nutritional Supplements and Mortality in Hemodialysis Patients: a Cluster-Randomized, Pragmatic Clinical Trial

* Use of central venous hemodialysis catheters can lead to catheter-related blood stream infection (HD-CRBSI). The REDUCCTION trial measured the rate of HD-CRBSI across Australia and tested the effect of a multifaceted, evidence-based intervention upon the rate of HD-CRBSI. After baseline data collection, clinics were randomly assigned to 1 of 3 time points (April 2018, Sept 2018, March 2019) for implementation of an intervention package based upon current evidence and guidelines. Preliminary analyses showed that 5,246 catheters (3,506 patients) were inserted with central venous catheters during the baseline phase and 4,610 catheters (3,144 patients) in the intervention phase. The package of interventions did not appear to reduce infection rates, but the infection rate across the overall program fell further from an already low baseline rate, over time. "These results show the importance of using such robust study designs to understand the effect of complex intervention packages in real world settings and embedding clinical trials within routine practice," said lead author Martin P. Gallagher, MBBS, FRACP, MPH (Hons), PhD, of The George Institute for Global Health and the University of Sydney. "Data from this national study will allow a better understanding of the reasons for variation in patients' risk of such infections."

Reducing the burden of dialysis Catheter Complications: a National approach (REDUCCTION)

* For patients undergoing dialysis, some form of anticoagulation is typically administered at the time of dialysis to prevent blood clotting during the procedure. In a clinical trial of 638 critically ill patients with acute kidney injury receiving dialysis, anticoagulation with regional citrate (which provides anticoagulation within the dialysis circuit without increasing the risk of bleeding) resulted in significantly longer dialysis filter lifespan compared with systemic heparin anticoagulation.

Regional Citrate vs Systemic Heparin Anticoagulation During Continuous Kidney Replacement Therapy Among Critically Ill Patients with Acute Kidney Injury: A Randomized Clinical Trial

* The Dapagliflozin And Prevention of Adverse outcomes in Chronic Kidney Disease trial (DAPA-CKD) assessed the sodium glucose co-transporter 2 inhibitor dapagliflozin in patients with chronic kidney disease (CKD) with and without type 2 diabetes. In the trial, 4,304 patients were randomized to receive dapagliflozin 10mg once daily or placebo. "We found that the drug delayed patients starting dialysis, reduced cardiovascular events, and reduced the number of deaths. The drug worked as well in patients without diabetes as those with diabetes," said lead author David C. Wheeler, MD, of University College London. Dapagliflozin also provided benefits regardless of the underlying cause of CKD.

Effects of dapagliflozin on kidney function, cardiovascular events and all-cause mortality according to cause of kidney disease in the DAPA-CKD trial

ASN Kidney Week 2020 Reimagined, the largest nephrology meeting of its kind, will provide a forum for more than 13,000 professionals to discuss the latest findings in kidney health research and engage in educational sessions related to advances in the care of patients with kidney and related disorders. Kidney Week 2020 Reimagined will take place October 19-October 25.

Since 1966, ASN has been leading the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients. ASN has more than 21,000 members representing 131 countries. For more information, visit http://www.asn-online.org.

The findings, simultaneously published in the New England Journal of Medicine and presented at the American Society of Nephrology's Kidney Week 2020 conference, show the investigational drug finerenone had tangible renal and cardiovascular benefits for patients with chronic kidney disease and type 2 diabetes.

The 5,700-person phase III trial was led by George Bakris, MD, Professor of Medicine at the University of Chicago and Director of the Comprehensive Hypertension Center at the University of Chicago Medicine. Taking place at more than 1,000 sites in 48 countries, the study was the largest-ever research effort into the disease that affects millions of people in the U.S. alone. More than 1/4 of adults with diabetes will eventually develop chronic kidney disease, making diabetes the leading cause of kidney failure.

"We now have evidence that doctors can safely slow diabetic kidney disease progression and reduce cardiovascular event rates using finerenone, a novel nonsteroidal mineralocorticoid receptor blocker, not yet approved by the FDA. This is very important for a group of patients who've historically had very few options," said Bakris. "This promising target for a new therapy means patients are able to delay dialysis and, in turn, further delay the possible need for kidney transplants. The reduction in cardiovascular events is an added bonus to slowing kidney disease progression."

Finerenone, which is made by Bayer, is a non-steroidal, selective mineralocorticoid receptor (MR) antagonist. The drug is not yet approved for use, but is being investigated in a number of clinical trials, including FIGARO that will be finished next year on cardiovascular outcomes. It directly targets and blocks receptors that contribute to inflammation and scarring of the heart and kidney. Kidneys filter waste and water from the body and also play role in controlling blood pressure and when they're damaged can lead to a backup of waste and fluid in the body.

Called FIDELIO-DKD (FInerenone in reducing kiDnEy faiLure and dIsease prOgression in Diabetic Kidney Disease), the study showed the drug was significantly better than a placebo, slowing the progression of kidney disease by 18% over a median of 2.6 years compared to current standard of care.

While patients who received finerenone did report higher levels of potassium (18% versus 9% with a placebo), serious potassium-related side effects requiring study discontinuation were infrequent and occurred in 2.8% of patients versus 0.9% of the control group. High levels of potassium can lead to cardiac rhythm problems

Bayer announced earlier this year that the trial met its composite primary renal endpoint and its composite key secondary cardiovascular endpoint. But full findings of the trial weren't released until Oct. 23. The trial was randomized, double-blind and placebo-controlled.

PHILADEPHIA--Treating lung cancer patients with proton therapy may help reduce the risk of radiation-induced heart diseases, suggests a new study from Penn Medicine. In a retrospective trial of more than 200 patients, mini-strokes were significantly less common among patients who underwent proton therapy versus conventional photon-based radiation therapy. Proton therapy patients also experienced fewer heart attacks.

Timothy Kegelman, MD, PhD, chief resident in the department of Radiation Oncology in the Perelman School of Medicine at the University of Pennsylvania, will present the findings on Sunday, October 25, at the American Society for Radiation Oncology virtual Annual Meeting (Abstract #1046).

"This shows us another potential benefit of proton therapy for lung cancer patients," Kegelman said. "We know proton has the ability to minimize radiation doses to surrounding organs like the heart. And these latest findings suggest that sparing correlates with fewer cardiac problems compared to conventional therapy."

Abigail T. Berman, MD, MSCE, as assistant professor of Radiation Oncology at Penn, serves as senior author on the study.

Cardiac toxicity from radiation therapy remains a significant concern for lung cancer patients. One strategy to minimize dose is the use of proton therapy, which has the ability to more precisely target tumors and spare adjacent vital organs and healthy tissue.

The study found that 1.1 percent of patients with locally advanced non-small cell lung cancer treated with proton therapy experienced post-treatment mini-strokes, also known as transient ischemic attacks, after a median follow up of 29 months compared to 8.2 percent of patients treated with photon radiation therapy. Myocardial infarctions were also less common in the proton therapy group compared to the photon group, though the difference was not statistically significant: 2.3 percent versus nine percent.

There was no difference in the number of cases of atrial fibrillation, coronary artery disease, heart failure, or stroke. The researchers continue to compare the two approaches by looking more closely at the severity of the cardiac events and radiation dose to specific parts of the heart. The analysis will help radiation oncologists have a better understanding of how to minimize these risks further with newer technologies.

A large prospective, international phase III clinical trial investigating the difference between proton therapy and photon therapy in lung cancer patients--which includes patients treated in Penn's Roberts Proton Therapy Center--has also been underway since 2014. The expectation is that protons will reduce cardiac-related morbidity and mortality, which will translate into a higher cure rate, the authors said. The trial is expected to complete patient accrual in 2022.

This study is the first experience suggesting a benefit of proton therapy over intensity modulated radiotherapy, or IMRT, in reducing cardiac dose effects.

"While these findings are promising and add to growing evidence, more research and the results of the randomized trial will help us better determine and understand how treating with protons may reduce cardiac event risk," Kegelman said.

Researchers at the Institut de Recerca Sant Joan de Déu (IRSJD) in collaboration with those at Centre for Genomic Regulation (CRG) have discovered that RING1B is a critical gene for the development of Ewing sarcoma, a rare type of developmental cancer that presents in bones and soft tissues. This newly uncovered epigenetic vulnerability in Ewing sarcoma cancer cells opens the door for new therapeutic strategies.

Ewing sarcoma is caused by a chromosomal translocation, where the EWSR1 gene in chromosome 22 fuses with most commonly the FLI1 gene in chromosome 11. The resulting EWSR1-FLI1 fusion protein, which contains the transcriptional activation machinery of EWSR1 and the DNA-binding domain of FLI1, is the main driver of tumorigenesis.

A new study published today in Science Advances describes how the oncogenic EWSR1-FLI1 fusion protein is directed to the different parts of the genome by RING1B, allowing EWSR1-FLI1 to hijack the transcriptional program of the cells, turning them into cancerous cells.

Researchers found that RING1B and EWSR1-FLI1 localize at the same regions in the genome, where RING1B is responsible for EWSR1-FLI1 recruitment. EWSR1-FLI1 cannot activate its target genes and transform a cell from healthy to cancerous state without RING1B, as shown by impaired tumour growth when RING1B is reduced.

Epigenetic inhibitors have been previously proposed to treat Ewing sarcoma and other types of paediatric cancers such as neuroblastoma, rhabdomyosarcoma or synovial sarcoma. Further research could explore the pharmacological inhibition of RING1B as a clinical therapy to treat Ewing sarcoma.

"Our findings offer striking insights into the mechanism of Ewing sarcoma, helping us get closer to uncovering the elusive cell-of-origin for this rare type of cancer," says Luciano Di Croce, researcher at the Centre for Genomic Regulation and one of the authors of the study. "All we have to do is look for high levels of RING1B."

"EWSR1-FLI1 remains a challenging druggable target, therefore understanding its dependencies may offer alternative strategies to switch off its aberrant transcriptional program," says Sara Sánchez-Molina, first author of the study and postdoctoral researcher at the Institut de Recerca Sant Joan de Déu.

"Ewing tumors are paradigmatic examples of developmental cancers, where the first hit (genetic or epigenetic) occurs during embryonic development (gestation) and, in the majority of Ewing sarcomas, develops postnatally during specific stages of growth like puberty. The study supports the model by which embryonic stem cells characterized by high levels of RING1B are capable to sustain the aberrant transcriptional program caused by the oncogenic fusion protein. Ewing sarcoma will develop if the individual is born with precursor cells bearing the fusion oncoprotein", says Jaume Mora, Scientific Director of the Pediatric Cancer Center Barcelona-Institut de Recerca Sant Joan de Déu, and director of the study.

Although the lungs are a common target for COVID-19's cytokine storm, so are the kidneys, making the 1 in 4 U.S. adults with diabetes resulting in diabetic kidney disease at increased risk for virus mortality.

But why are the kidneys so attractive to the coronavirus?

Recently published in Kidney International, a national research team made up of kidney clinicians, bioinformaticians, a molecular biologist, pathologist and virologist found that a protein on the surface of some kidney cells, called angiotensin-converting enzyme 2 (ACE2), is the primary COVID-19 entry receptor and aids in the activation of its uncontrolled immune response.

It also is responsible for the virus' duplication, leaving patients sicker, longer.

Since higher levels of ACE2 expression on cells correlates with higher risk of serious COVID-19 illness, Matthias Kretzler, M.D., a study author and nephrologist at Michigan Medicine, sought out to learn more about which kidney cells create elevated levels of this protein and why, as well as if the molecular process of the vulnerable cells is similar to those in patients with COVID-19.

Using machine learning technology developed by study author Olga Troyanskaya, Ph.D., from Princeton University, the researchers were able to identify and categorize groups of genes that produced higher ACE2 expression levels in three different subject groups: healthy, living kidney donors (18 participants), those with diabetic kidney disease (44 participants) and those hospitalized with COVID-19 (13 participants.)

After analyzing more than 110,000 different cells in the three groups, Kretzler and the team identified networks of molecules that result in higher levels of ACE2.

"Being able to characterize these molecular processes may help scientists quickly identify and develop therapies to lessen the risk of serious illness for patients, or even prevent COVID-19 infection from damaging the kidney," Kretzler says.

The groups shared a few molecular similarities, but one would become the focus of the researchers: ACE2 was predominantly expressed in cells that also expressed markers of specialized transport epithelial cells in the proximal tubules.

This area of the kidney is responsible for reabsorbing nutrients during the kidney's filtration process.

Using machine learning technology

Using kidney biopsies from the healthy kidneys and those with diabetic kidney disease, and kidney cells retrieved from the urine samples of COVID-19 patients, the machine learning technology allowed the research team to pinpoint in what kidney cells ACE2 is found and what characteristics these cells have.

Cells that express the virus receptor, ACE2, were found to be "locked and loaded" for the virus, meaning many other proteins are found with ACE2 which interact with viruses during infection.

This wasn't only true in the COVID-19 infected patients, but also in kidneys from patients with diabetes. When comparing the kidney cells of COVID-19 patients with those with diabetic kidney disease, similar molecular processes were activated in both that would trigger severe COVID-19 illness.

"Diabetic kidney disease, by nature, primes kidney cells in a way that can make them vulnerable to COVID-19," Kretzler says. "In conjunction with COVID-19 and its inflammatory nature, serious kidney damage can occur."

What we know and don't know

Discovering the importance of the proximal tubules epithelial cells in its relation to the severity of COVID-19 illness opens a door for novel therapeutics to address COVID-19 and its related kidney injury.

"We weren't sure before this study if medications commonly used to treat hypertension and diabetic kidney disease increase the risk of COVID-19 infection. There was a serious concern from colleagues and my patients about how these medications affect ACE2 in the kidney," Kretzler says.

Now, the team can confidently conclude these medications won't harm those with diabetic kidney disease, providing reassurance for patients to continue to take these live saving medicines.

However, further studies need to look at a population that has both diabetic kidney disease and COVID-19. Kretzler confirms these are underway.

"To help in the global research response to COVID-19, we made our data available to scientists around the world so that they can use the information from our patients to help identify novel ways to treat patients in the pandemic," Kretzler says. "Our team is focused now on learning how treatments given to COVID-19 patients affect kidney cells, so we can offer the best medications to patients with COVID-19 and kidney disease in the ongoing pandemic."

People with diabetes -- especially the 20 to 40 percent with diabetic kidney disease -- are among the most at risk for serious complications and death from COVID-19. A new study of gene expression utilizing machine learning peered inside the kidney cells of COVID-19 patients and diabetic kidney disease patients and made a surprising discovery: Similar molecular processes were activated in both sets of patients, revealing potential avenues of viral vulnerability. The researchers report their findings in Kidney International.

The results suggest that diabetes may predispose patients to infection with the novel coronavirus or to more severe COVID-19 by spurring biological processes used by the virus to infect and replicate. The same study found that medications commonly used to treat hypertension and diabetic kidney disease probably don't increase coronavirus infection risk, despite initial concerns about drug interactions with viral entry pathways.

"Our hypothesis is that diabetes primes these kidney cells in some way that makes them especially vulnerable to COVID," says study co-author Aaron Wong, a data scientist and project leader at the Flatiron Institute's Center for Computational Biology (CCB) in New York City. The new findings will help guide strategies to reduce the risk of COVID-19 to diabetics, he says.

The research was led by Olga Troyanskaya, deputy director of genomics at the CCB and a professor at Princeton University, and Matthias Kretzler, a nephrologist and a professor at the University of Michigan's academic medical center, Michigan Medicine. Wong is co-lead author of the study along with the CCB's Rachel Sealfon, Princeton's Chandra Theesfeld, and Michigan Medicine's Rajasree Menon, Edgar Otto and Viji Nair.

The coronavirus responsible for COVID-19, dubbed SARS-CoV-2, is best known for targeting cells in the respiratory system. However, the virus can also invade cells in organs such as the heart and kidneys. The virus infiltrates cells by latching on to a protein called angiotensin-converting enzyme 2, or ACE2. This viral piggybacking prompted the hypothesis that cells that produce lots of ACE2 are more vulnerable to infection. The researchers set out to find which kidney cells had elevated ACE2 levels and what made those cells extra vulnerable in diabetic kidney disease patients.

The researchers started by measuring ACE2 levels and gene expression in cells taken from biopsies from healthy kidney donors and patients with diabetic kidney disease. Kidney biopsies weren't an option for COVID-19 patients, so the researchers looked instead at kidney cells in urine samples from COVID-19 patients with kidney damage. These provided a unique look inside the organ without invasive procedures. Analyzing the samples, the researchers found ACE2 expression primarily in proximal tubule epithelial cells. These cells play a major role in the reabsorption of substances such as water, salt, glucose and amino acids by the kidneys.

Only around one-fifth of the proximal tubule epithelial cells had detectable ACE2 and were therefore vulnerable to infection. So what made those cells so vulnerable to COVID-19 in diabetic kidney disease patients? To find out, the researchers looked at which biological processes ramp up in ACE2-expressing cells. To identify these pathways in the vast complexity of cellular circuitry, researchers used the HumanBase.io system developed by Troyanskaya's group at the CCB. HumanBase uses machine learning to identify biological connections between genes and pinpoint functionally related groups of genes (called modules) in the context of specific tissues, cell types and diseases. "HumanBase is what made this analysis possible," Troyanskaya says.

HumanBase identified several modules linked to ACE2 production in COVID-19 patients. Those modules were associated with processes related to a cell's reaction to viral invasion, the activation of immune responses, and viral replication. Surprisingly, those same modules were also present in patients with diabetic kidney disease. "The cells in the diabetic kidney patients looked a lot like the cells in the COVID-19 patients," says Sealfon, "with many genes upregulated that respond to or are engaged by viruses."

The consequences are twofold: Diabetic kidney disease could make cells more vulnerable to the coronavirus, and diabetic kidney disease and COVID-19 may compound each other's effects, potentially triggering a severe immune response that causes kidney damage.

The researchers also found that ACE2 levels were unaffected by drugs known as renin-angiotensin-aldosterone system inhibitors, which are commonly used to treat hypertension and diabetic kidney disease. These drugs modulate ACE or inhibit the pathway used by the protein. "At the beginning of the pandemic, there was a back-and-forth about whether patients should stop taking these ACE pathway modulators because they might increase the risk of infection," Theesfeld says. "Now a few studies, including ours, show that they should keep taking their medicines."

The results come with a major caveat, though. The study looked at the gene expression in kidney cells from patients with diabetes or COVID-19, but not both. More work is needed to confirm how the two illnesses behave in tandem. The researchers say that the next step is to look at kidney tissues affected by both diabetic kidney disease and COVID-19. Such a study could help identify whether specific therapies could reduce COVID-19 susceptibility and progression in diabetic kidney disease patients.

A new mathematical modeling study by Ashish Goyal and colleagues, informed by data collected from 25 patients hospitalized with COVID-19 in 4 different countries, offers some important new insights into the optimal timing of 4 different antiviral therapies to combat the disease. The results indicate that treatment with either of two small molecule drugs (remdesivir and selinexor), broadly neutralizing antibodies, or cellular immunotherapy may reduce the duration of viral shedding and the intensity of immune responses when administered after peak viral load, at the typical onset of symptoms. However, this timing may not have an appreciable impact on viral "area under the curve" (AUC), a measure of total viral load as a function of time over the entire duration of infection. Instead, administration of a strongly potent antiviral therapy before peak viral load, during the pre-symptomatic phase of infection, will likely provide the greatest suppression of viral AUC, Goyal et al. suggest. The authors warn, however, that administering a moderately potent antiviral agent on this same timeframe could result in drug resistance. Absent a vaccine or widespread herd immunity, antiviral therapies may be able to lessen the severity of the COVID-19 pandemic. However, most information regarding the efficacy of various antivirals to combat COVID-19 has come from empirical evidence - which to date has proven scarce, the authors say. Seeking to close this knowledge gap, Goyal et al. developed a mathematical model based on four datasets of SARS-CoV-2 viral shedding and viral load from 25 infected people: 11 from Singapore, 9 from Germany, 1 from South Korea, and 4 from France. They then applied the model individually to four separate antiviral therapies: the small molecule drugs remdesivir and selinexor, broadly neutralizing antibodies, and cellular immunotherapy. The authors conclude that their model "provides a broad platform for assessment of all major types of therapies," even as they note some important limitations. "Most critically, [our model] cannot be used to predict trial outcomes but rather establishes important principles to consider when designing and interpreting trials," they say. A key question when deciding when and how to deploy various therapies, they note, will be to determine whether duration of viral shedding or viral AUC is more relevant for assessing COVID-19 severity. "If AUC is most predictive of poor outcomes, then all forms of antiviral therapy outside of potent [post-exposure prophylaxis] are unlikely to provide clinical benefit," Goyal et al. write. "However, if shedding duration is the best surrogate, then an early test and treat approach is highly promising for limiting the likelihood of severe disease."

An experimental vaccine, designed to enlist the body's own immune system to target cancer cells, has shown promise for treating and preventing cancer in mice.

The vaccine was created to target a gene called KRAS that is involved in the development of many types of cancer, including lung, bowel and pancreatic cancer.

Researchers from the same team have also found a new way to spot and treat aggressive forms of lung cancers that are able to evade the body's immune system.

Both studies will be presented on Sunday at the 32nd EORTC-NCI-AACR [1] Symposium on Molecular Targets and Cancer Therapeutics, which is taking place online.

Scientists have known for decades that the KRAS gene goes wrong - or mutates - in many cancers. However, until now, researchers have struggled to find a way to turn this knowledge into an effective treatment.

The vaccine study [2] was carried out by Dr Rachel Ambler, a postdoctoral research fellow, and colleagues at The Francis Crick Institute, London, UK. She said: "We know that if KRAS goes wrong, it enables cells in our bodies to start multiplying and turning into cancer cells. Recently, we've learned that, with the right help, the body's immune system might be capable of slowing this growth.

"We wanted to see if we could use this knowledge to create a cancer vaccine that could not only be used to treat cancer, but also give long-lasting protection against cancer, with minimal side-effects."

Dr Ambler and her colleagues created a set of vaccines that are capable of stimulating an immune response towards the most common KRAS mutations.

The vaccines are made up of two elements joined together. One element is a fragment of the protein produced by cancer cells with a mutated KRAS gene. The other element is an antibody that helps to deliver the vaccine to a cell of the immune system called a dendritic cell. These cells play a key role in helping the immune system spot and destroy cancer cells, an ability that could be boosted by the vaccines.

The team tested the vaccine on mice that already had lung tumours and mice that were induced to grow tumours. Researchers studied the mice for indications that their immune systems were responding to the vaccine and for signs that tumours were shrinking or not even forming in the first place.

In mice with tumours, 65% of those treated with the vaccine were alive after 75 days, compared to 15% of mice that were not given the vaccine.

In mice treated to induce tumours, 40% of vaccinated mice remained tumour-free after 150 days, compared to only 5% of unvaccinated mice (one mouse). By vaccinating the mice, researchers found that the appearance of tumours was delayed by an average of around 40 days.

Dr Ambler said: "When we used the vaccine as a treatment, we found that it slowed the growth of cancers in the mice. And when we used it as a preventative measure, we found that no cancers grew in the mice for quite a long period of time and, in many cases, cancers never developed.

"Previous trials of cancer vaccines have failed because they have not been able to create a strong enough response from the immune system to find and destroy cancer cells. This research still has a long way to go before it could help prevent and treat cancer in people, but our results suggest that the design of this vaccine has created a strong response in mice with very few side-effects."

Researchers from the same team have also made an important discovery about how lung cancers are able to evade the body's immune system, making them harder to treat. Their findings will be discussed in two further presentations at the 32th EORTC-NCI-AACR Symposium. [3,4]

Dr Sophie de Carné, a postdoctoral researcher, and Dr Phil East, deputy head of bioinformatics, from The Francis Crick Institute used a collection of hundreds of human tumour samples with information on which genes are mutated and which genes are active inside the tumours. They were also interested in the KRAS gene and its role in the development of hard-to-treat cancers.

Dr de Carné said: "In patients with some of the most aggressive cancers, we discovered that the activity of the KRAS gene results in the build up of a chemical called adenosine. Higher levels of adenosine are known to dampen the body's immune response, making it harder for immune cells to target and destroy cancer cells."

The researchers then studied cancers with similar KRAS activity in mice to see whether it was possible to manipulate the levels of adenosine to make it easier to treat the cancer. By giving the mice a drug designed to lower adenosine, oleclumab made by AstraZeneca, alongside existing cancer drugs that help the immune system fight cancer, the researchers found that they could improve survival.

Dr East added: "Together these results suggest it could eventually be possible to identify patients who have this aggressive type of lung cancer and use a combination of drugs to support their immune system and successfully treat their tumours."

Dr James L. Gulley is co-chair of the 32th EORTC-NCI-AACR Symposium for the NCI and Director of the Medical Oncology Service, Center for Cancer Research, NCI, USA, and was not involved in the research. He said: "These studies focus on types of cancer - such as lung and pancreatic cancer - that are difficult to treat. Survival rates for these cancers remain very poor so we urgently need new treatments for patients.

"Boosting the immune system with drugs to treat cancer or even developing a vaccine to prevent cancer are both exciting possibilities, especially if they can be achieved with minimal side effects. We hope that these promising approaches will one day be reproduced in patients."

Scientists cannot be expected to drop everything they're working on to turn their attention to beating COVID-19, according to the winner of the 2019 Nobel Prize in Physiology or Medicine, Professor Sir Peter Ratcliffe.

Speaking before he delivered the prestigious Michel Clavel lecture to the 32nd EORTC-NCI-AACR [1] Symposium on Molecular Targets and Cancer Therapeutics, which was due to take place in Barcelona, Spain, and was moved online because of the coronavirus pandemic, Sir Peter said: "There is a belief in some quarters that the whole world of science should stop what it's doing and work on coronavirus. I would argue that the best description of what we do is passion-driven research. The investigator has a passion for what they do, they have self-belief that they can solve a particular problem, and they have some belief that the problem is important, and that's what drives us all on."

He pointed out that much of the technology that has been turned to deal with COVID-19 emanated from cancer research, such as knowledge about how viruses infect cells, the immune response, how to engineer viral proteins to create potential vaccines, and some of the diagnostic tests for the coronavirus. However, researchers, like one of the world's greatest footballers, need to work on what they feel passionate about.

"Messi would play football regardless of how much he is paid. That's what you're harnessing in science; it's that human passion that some people have to push themselves and to find things out. If you have a problem like coronavirus and people say you have to work on coronavirus it doesn't always harness that passion," he said.

Spain is not only home to a great footballer, but also to many researchers who have paved the way for Sir Peter's research on how cells sense and adapt to oxygen availability. Low levels of oxygen in cells, known as hypoxia, is an important component of many human diseases, including cancer, heart disease, stroke, vascular disease and anaemia. Hypoxia is common in solid tumours, and is associated with treatment resistance and poor prognosis.

Sir Peter said: "Spain has had a long history of hypoxia research, going back to Fernando De Castro in the 1920s who should have won the Nobel Prize but didn't because his work was overlooked, partly because of the problems created by the Spanish Civil War. Spain has always been strong in this field."

De Castro was the first person to describe cells specifically devoted to detecting changes in the chemical composition of blood as part of his research into the carotid body - a small structure that monitors changes in oxygen content in the blood and helps to control respiratory activity.

Together with Gregg Semenza and William Kaelin, Sir Peter won the 2019 Nobel prize for their discoveries about the molecular machinery that regulates the activities of genes in response to varying levels of oxygen.

In his lecture to the 32nd EORTC-NCI-AACR Symposium, Sir Peter, who is professor of clinical medicine at the University of Oxford and clinical research director at the Francis Crick Institute in London, UK, will describe 30 years of research that led to his discoveries.

"There were two major aspects to the discovery that led to the Nobel. The first was the recognition that there are systems in the body's cells for direct sensing of oxygen. It's important because oxygen has to be delivered in precisely the right amounts to about 40 trillion cells in the human body and that's not straightforward. Dysregulation, usually lack of oxygen, is a component of almost all human diseases including heart disease, circulatory diseases and cancer.

"The second part of the discovery was that we defined the mechanism by which that occurs and that was an unanticipated mechanism in cell signalling by which an oxygen-splitting enzyme, a dioxygenase, which is a biological catalyst, uses oxygen to mark the protein that directs gene expression; that protein is called hypoxia inducible factor, and that's what Gregg Semenza discovered, and William Kaelin and I discovered the oxygen splitting mechanism.

"It's important since enzymes are classically drug targets and, indeed, this enzyme is now a drug target, as is the HIF protein that it modifies and which directs gene expression. The work so far has entrained two sets of drug discovery programmes, both of which have led to drugs that are either in clinical practice or in clinical trials. One group of drugs aims to activate the system, to make the body think it's hypoxic when it's not and make corrective responses. Those corrective responses are currently being used to treat anaemia, particularly the anaemia that occurs in kidney disease where the patients lack a hormone called erythropoietin. They are also being used to treat other aspects of disease where low oxygen is a problem, such as in heart, lung or circulatory disease.

"The other class of drug is designed to antagonise the hypoxic response and those drugs are being used in cancer where it's believed that hypoxia is actually driving the cancer development. When cancer grows rapidly, it often outgrows its oxygen supply and therefore it gets low oxygen inside the growing tumour. Low oxygen sets off this HIF system and aspects of the system have the ability to promote cancer. It's possible by reducing the activity of the hypoxia inducible system to retard the growth of cancer and those drugs are looking pretty promising in the treatment of kidney cancer.

"These drug targets provide many potential uses and opportunities in medicine, but also difficulties in accurately defining what a drug will do in the body even when you know exactly what you're targeting."

[1] EORTC [European Organisation for Research and Treatment of Cancer, NCI [National Cancer Institute], AACR [American Association for Cancer Research]. The Symposium takes place online on 24-25 October.

FINDINGS

Untreated HIV infection is linked with epigenetic changes that suggest rapid aging. A new study by UCLA researchers shows that antiretroviral therapy given over two years was unable to completely restore age-appropriate epigenetic patterns, leaving patients more susceptible to aging-related illnesses.

BACKGROUND

This is the first longitudinal study conducted to investigate the contribution of HIV-infection, versus treatment, on the acceleration of aging epigenetics -- external factors that affect the function of genes -- in this population of adults.

METHOD

The researchers extracted DNA from 15 HIV-infected people at three points in time: 6 to 12 months prior to the initiation of antiretroviral therapy, 6 to 12 months after the beginning of therapy and, again, 18 to 24 months after being put on the therapy. They then compared those samples with DNA from 15 age-matched, non-HIV-infected individuals.

The researchers note some limitations to the study, including the small sample size, their inability to adjust for other factors that might have influenced the results, and the fact that a larger study may be needed to detect more subtle epigenetic changes caused by antiretroviral therapy.

IMPACT

The results suggest that altered epigenetics may help explain why even successfully treated HIV-infected adults are at an increased risk for the early development of many diseases more commonly associated with aging.

Modelling analysis of measures in 131 countries confirms that combined measures are likely to reduce the R more than individual measures.

Authors looked at four possible combinations of measures, with the least comprehensive package of measures (ban on public events and gatherings of more than ten people) reducing R by 29% on day 28, increasing to a 52% reduction for the most comprehensive package similar to a lockdown.

The study estimated that there was a 1 to 3 week delay in the effect of imposing or lifting measures on the R number.

Authors caution that their study was not able to account for other potentially influential factors, like mask wearing, and non-compliance with measures.

Analysis suggests that individual measures (including school closure, workplace closure, public events ban, ban on gatherings of more than ten people, requirements to stay at home, and internal movement limits) are associated with a reduction in transmission of SARS-CoV-2 but combined measures are more effective at reducing transmission, according to a modelling study published in The Lancet Infectious Diseases journal.

The study estimates the effect individual measures and four combinations of measures (ranging from a ban on events and gatherings of more than ten people to a more restrictive combination of measures resembling a lockdown) has on the R number up to 28 days after being introduced or lifted.

The R number - or reproduction number - is a key measure of virus transmission. An R value above 1 indicates a growing outbreak, whereas an R value below 1 indicates a shrinking outbreak.

Using data from 131 countries, the study provides a high-level overview of the effects of population-level intervention measures, but does not account for other potentially influential factors that have an impact on R- including, among other things, compliance with the interventions, changes in population behaviour (eg, wearing of face masks), sub-national differences in R, or the effects of contact tracing and isolation - all of which vary by context. Using the R number as a proxy for transmission also has limitations, as it is difficult to estimate accurately, particularly when prevalence is low.

Professor Harish Nair, University of Edinburgh, UK, says, "We found that combining different measures showed the greatest effect on reducing the transmission of COVID-19. As we experience a resurgence of the virus, policymakers will need to consider combinations of measures to reduce the R number. Our study can inform decisions on which measures to introduce or lift, and when to expect to see their effects, but this will also depend on the local context - the R number at any given time, the local healthcare capacity, and the social and economic impact of measures." [1]

When looking at the measures individually, a ban on public events was associated with the greatest reduction in R (24% reduction after 28 days), which the authors suggest may be because they are likely to prevent super spreader events and it was often the first measure to be introduced in countries.

The measures most strongly associated with an increase in R were lifting bans on gatherings of more than ten people and re-opening of schools (25% and 24% after 28 days). Although reopening schools was associated with a 24% increase in the R by day 28, the authors caution that they were unable to account for different precautions some countries implemented for reopening schools (eg, limiting class sizes, distancing measure, routine deep cleaning, personal handwashing, face masks, and thermal temperature checks on arrival), which are essential for safer school reopening and should be taken into account when interpreting this finding.

On school reopening, Professor Nair adds, "We found an increase in R after reopening schools but is not clear whether the increase is attributable to specific age groups, where there may be substantial differences in adherence to social distancing measures within and outside classrooms. Furthermore, more data are needed to understand the specific role of schools in increased SARS-CoV-2 transmission through robust contact tracing." [1]

Studies have found that measures, including school closure, social distancing, and lockdown (a combination of all measures), could reduce R substantially to near or below 1, but this is the first study to look at the effects on R following the relaxation of these measures.

In this modelling study, data on daily country-level estimates of R were linked with data on what measures those countries had in place from January 1, 2020 to July 20, 2020. The timeline of each country was divided into individual phases when all measures remained the same in that country. The analysis included 790 phases from 131 countries and the authors used a model to measure the association between which measures were in place and changes in the R. They used this to estimate the effect up to 28 days on the R of introducing or lifting measures. In addition, they modelled four combinations of measures that could be introduced to tackle the resurgence of SARS-CoV-2.

A decreasing trend over time in the R was found following the introduction of five individual measures, with a reduction in R 28 days after banning public events (24%), school closures (15%), workplace closure (13%), internal movement limits (7%), and requirements to stay at home (3%). However, when each of these measures were introduced individually, the only one to have a statistically significant effect on the R number was a public events ban. [2]

Modelling the effect of imposing four combinations of measures was linked to greater reductions in the R number after 28 days. The least comprehensive package of measures (bans on public events and gatherings of more than ten people) reduced R by 29% on day 28. The second package (workplace closure plus ban on public events and gatherings of more than ten people) reduced R by 38% on day 28. The third package (workplace closure, ban on public events and gatherings of more than ten people, and internal movement limits) reduced R by 42% on day 28. The most comprehensive package (school and workplace closure, ban on public events and gatherings of more than ten people, internal movement limits and a stay at home requirement) reduced it by 52%. [3]

The effect of introducing measures was not immediate; it took an average of 8 days after introducing a measure to see 60% of its effect on reducing the R number.

The authors also looked at the impact of lifting measures. An increasing trend in R was found following the relaxation of five measures, with an increase after 28 days for the lifting of bans on public gatherings of more than ten people (25%), school closures (24%), public events ban (21%), and internal movement limits (13%), and requirements to stay at home (11%). However, the increase was significant only for reopening school and lifting bans on public gatherings of more than ten people. [2]

Similarly, the effect of lifting measures was not immediate; it took an average of 17 days to see 60% of its effect on increasing the R number.

In addition, the authors did a secondary analysis which modelled the total visits to workplaces and the total time spent in residential areas using Google mobility data among 101 countries. Google Mobility data suggests that people took a similar time to adapt their behaviour to comply with workplace closures and stay at home requirements as the delay between the measures and the effects seen on R. Therefore, they suggest that delays could be explained by the population taking time to modify their behaviour to adhere to measures. [4]

The authors note that some of the greatest effects on R were seen for measures that are more easily implementable by law, like school reopening and introduction of a public events ban. They suggest that the effect of these measures may be because their effects are more immediate, and compliance is easier to ensure. For example, when schools reopen, the majority of children return, and change is immediate, compared with say lifting of internal movement limits or requirements to stay at home, as there is a need for change in population behaviour, which takes time and cannot be measured in the datasets they used.

Likewise, the authors suggest that low compliance with bans on gatherings of more than ten or more than 100 people may be a possible reason why they did not find a substantial reduction in transmission after this measure being introduced. In addition, they note that they were unable to distinguish between indoor versus outdoor gatherings in this measure due to lack of data.

Writing in a linked Comment, Professor Chris T Bauch from University of Waterloo, Canada, says, "Despite R's imperfections, the findings of Li and colleagues tell us that NPIs [non-pharmaceutical interventions] work and which ones work best. This information is crucial, given that some NPIs have massive socioeconomic effects. In a similar vein, transmission models that project COVID-19 cases and deaths under different NPI scenarios could be highly valuable for optimising a country's portfolio of NPIs. Moreover, I think R provides a social utility that epidemiologists can easily overlook. The success of large-scale NPIs requires population adherence. R can stimulate populations to act and gives them useful feedback on the fruits of their labour. Perhaps this is one reason that R has entered our vernacular in 2020."

Highlights

Adults with glomerular diseases have a 2.5-times higher risk of developing cardiovascular disease than individuals in the general population.

Results from the study will be presented online during ASN Kidney Week 2020 Reimagined October 19-October 25.

Washington, DC (October 24, 2020) -- Adults with glomerular diseases--which affect the kidney's filtering units where blood is cleaned--face a high risk of developing heart problems, according to a study that will be presented online during ASN Kidney Week 2020 Reimagined October 19-October 25.

Cardiovascular disease is a leading cause of morbidity and mortality in adults with reduced kidney function. To define the cardiovascular disease risk of patients with glomerular diseases--which include focal segmental glomerulosclerosis, membranous nephropathy, IgA nephropathy, and minimal change disease--investigators analyzed 2000-2012 information from a centralized kidney pathology registry in British Columbia, Canada.

Among 1,912 patients followed for a median of 6.8 years, there were 338 cardiovascular events, and the 10-year risk was 16.0% (7.7% for IgA nephropathy, 13.2% for minimal change disease, 19.4% for membranous nephropathy, and 27.0% for focal segmental glomerulosclerosis). Results showed cardiovascular event rates were high both prior to and after end stage kidney failure.

The risk of cardiovascular disease was 2.5-times higher in individuals with glomerular diseases compared with adults in the general population.

"Consideration of glomerular disease-specific factors can help improve cardiovascular risk prediction. Failure to take these novel factors into account will lead to underestimation of cardiovascular risk and underutilization of cardiovascular primary prevention strategies," said lead author Heather Gunning (University of British Columbia). "Further research is ongoing into the impact of glomerular disease activity and therapy over time on cardiovascular risk. This will allow better understanding of the impact of glomerular disease on cardiovascular risk and whether treatment may modify this."

Study: "The Risk of Cardiovascular Events is Higher in Patients with Glomerular Disease Compared to the General Population"

ASN Kidney Week 2020 Reimagined, the largest nephrology meeting of its kind, will provide a forum for more than 13,000 professionals to discuss the latest findings in kidney health research and engage in educational sessions related to advances in the care of patients with kidney and related disorders. Kidney Week 2020 Reimagined will take place October 19-October 25.

Washington, DC (October 22, 2020) -- A recent study has validated a new patient-reported outcome measure that assesses fatigue in patients receiving long-term dialysis treatments. The results appear in an upcoming issue of CJASN.

Fatigue, which affects most patients with kidney failure who receive hemodialysis, contributes to poor quality of life and is associated with higher risks of cardiovascular disease, depression, and early death. Unfortunately, fatigue can be difficult to quantify. To address this, Angela Ju, PhD (University of Sydney, in Australia) and her colleagues developed a patient-reported measure of fatigue-- called Standardized Outcomes in Nephrology-Hemodialysis (SONG-HD) Fatigue--and evaluated its potential in 485 adults receiving hemodialysis in the United Kingdom, Australia, and Romania. SONG-HD Fatigue calculates the average fatigue over a period of 1 week, and it gauges tiredness, energy, and the impact of fatigue on life participation.

"Currently, fatigue is assessed in a wide range of different ways using measures that vary in terms of content, length, reliability, and validity. Most are quite lengthy, and it is unclear which measure is the best to use," said Dr. Ju. "This makes it difficult for researchers to choose how to assess fatigue, and compare effectiveness of interventions evaluated in different studies."

The study assessed SONG-HD Fatigue in accordance with the recommended US Food and Drug Administration guidelines for patient-reported outcome measures. The authors concluded that it appears to be a reliable and valid measure to be used in trials involving patients receiving hemodialysis.

"Establishing a core outcome measure for fatigue will allow researchers to do 2 important things: to quickly and accurately assess the impact a new intervention has on fatigue as experienced by patients receiving hemodialysis, and to allow the comparison of interventions across different trials to see which one is superior in terms of its effect on fatigue," Dr. Ju said. "Patients want to know about fatigue regardless of whether or not the intervention was designed to affect it. The core outcome measure helps to provide this information. Interventions specifically targeting fatigue will require a more comprehensive measure."

An accompanying editorial notes that "patients on maintenance hemodialysis have been very clear that fatigue is an important problem for them. Investigators such as Ju and colleagues have heard them. Now it is time for all us, clinicians and researchers alike, to do the same."

A Patient Voice also accompanies the study and provides the perspective of a psychologist who has late-stage chronic kidney disease.

GRAND RAPIDS, Mich. (Oct. 22, 2020) -- Scientists have developed a simple, experimental blood test that distinguishes pancreatic cancers that respond to treatment from those that do not. This critical distinction could one day guide therapeutic decisions and spare patients with resistant cancers from undergoing unnecessary treatments with challenging side effects.

The findings were published today in Clinical Cancer Research, a journal of the American Association for Cancer Research.

"Knowing which type of pancreatic cancer a person has is critical to implementing the right treatment strategy for each patient," said Brian Haab, Ph.D., a professor at Van Andel Institute and corresponding author of the study. "We hope that our new test, which detects a marker produced by cancer cells of one subtype and not the other, will one day soon be a powerful tool to help physicians and patients make the best decisions possible."

Pancreatic cancers are among the most challenging malignancies to treat, due in part to their ability to evade detection until they have advanced and spread. Physicians currently have no reliable way to determine whether a patient has a subtype that will respond to existing chemotherapies versus a subtype that is resistant to treatment. The result often is a blanket treatment approach that works in only some but can have side effects in all.

The test detects and measures the levels of a sugar called sTRA, which is produced by a certain subtype of pancreatic cancer and escapes into the blood stream. Pancreatic cancers that produce sTRA tend to not respond to chemotherapy.

The new sTRA test evolved from an earlier test announced in January 2019. In that study, also published in Clinical Cancer Research, Haab and his colleagues described an experimental blood test that combined an existing diagnostic that detected a sugar called CA19-9 with a new test that detected sTRA. The combination approach detected nearly 70% of pancreatic cancers with a less than 5% false-positive rate -- roughly 30% more than the CA19-9 alone. Both the 2019 combination test and the new sTRA test are slated to undergo additional clinical validation.

"The 2019 combination test tells us whether there is cancer and the new sTRA test helps us determine what kind of pancreatic cancer, which then could allow physicians to better narrow down the appropriate treatment plan," Haab said. "When used in sequence, we believe the combination test and the new sTRA test could help catch and identify pancreatic cancer more quickly and definitively."

With nearly half of the world's population at risk for life-threatening malaria infections, University of Maryland School of Medicine (UMSOM) researchers and their colleagues identified an important public health measure to control the disease. Use of preventive antimalarial treatments reduces by half the number of malaria infections among schoolchildren, according to a new analysis published today in The Lancet Global Health. Preventive treatment also reduces cases of anemia among schoolchildren by 15 percent and is associated with improved learning in children older than 10 years.

The study was the first meta-analysis of its kind and included 15,000 schoolchildren across seven African countries. It was conducted by an international consortium of 33 researchers from 15 institutions led by UMSOM and the London School of Hygiene & Tropical Medicine.

An estimated 3.4 billion people worldwide are at risk of contracting malaria, and 400,000 die from the disease every year, according to the World Health Organization (WHO). While the WHO recommends providing intermittent preventive treatment to pregnant women, infants and young children in some malaria-endemic areas, they have not issued recommendations for school-age children despite growing evidence that use of these preventive mediations works to prevent infections and improve health.

Malaria is transmitted by mosquitos infected with a parasite and remains prevalent in Africa, Central and South America, and Southeast Asia. Malaria can cause fevers, headache and chills, as well as anemia due to the parasite's destruction of red blood cells. Anemia can cause severe fatigue, headaches, delayed development and poor performance in school. Malaria can also lead to organ failure and can be fatal if left untreated.

"We have overlooked the burden of malaria in school-age children. The resulting chronic illness and anemia can impair development and lead to cognitive problems making it tougher to pay attention or learn in school," says lead author Lauren Cohee, MD, an Instructor of Pediatrics and faculty member in the Malaria Research Program in the Center for Vaccine Development and Global Health at the University of Maryland School of Medicine. "Children may also play an important role in disease transmission and by treating their infections, we may have substantial public health consequences on the surrounding populations."

In the journal article, Dr. Cohee and her colleagues pointed out that public health campaigns to provide antimalarial medications to school-aged children may be a way to improve the health and wellness of children, but to curb the disease spread in communities where malaria is endemic.

For their current study, the school-age malaria study group combined data on 15,658 research participants from 11 different clinical studies that tested malaria preventative medications in children ages 5 to 15 years. The children were from seven different countries in sub-Saharan Africa; 8,437 children were given malaria preventives, and 7,221 participants were either not treated or were given a placebo as a control.

Doses of preventive drugs were given as often as once a month or as infrequently as once a year depending on the study. The children were monitored for an average of 43-weeks. Six of the clinical trials evaluated cognitive function between children who received the malaria preventives and those who did not.

Preventive malaria drugs can cause side effects such as nausea, vomiting, upset stomach, headache or weakness, and all 11 studies did report instances of these symptoms. No serious side effects, however, were reported in any of the studies.

Dr. Cohee noted that preventive treatment of malaria could be added to existing school-based health programs, including nutrition and deworming, to further promote the overall health of the learner. "Utilizing schools as a platform to deliver preventive treatment improves the feasibility of this intervention and builds upon the ever increasing rates of primary school enrollment across the malaria endemic world," Dr. Cohee said.

"More than 200 million children in Africa alone are at risk of becoming infected with malaria and in some regions more than 50 percent of them will ultimately contract it," says E. Albert Reece, MD, PhD, MBA, Executive Vice President for Medical Affairs, University of Maryland Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor and Dean, University of Maryland School of Medicine. "We must continue to promote research-based interventions that will improve the health and wellness of our world's children."