Acute gastroenteritis is a common infectious disease in children aged under 6 years. Although it often resolves on its own, it has a high consultation rate in primary care, especially during out-of-office hours. In a study published in The Annals of Family Medicine, Dutch researchers interviewed parents who contacted GPs outside of normal hours, and found that who felt misunderstood or ignored were more likely to request a visit.
The researchers conducted 14 semi-structured interviews with parents who contacted primary care physicians outside of normal operating hours seeking medical attention for their children. They sought to explore parental motivations, expectations, and experiences of off-hours primary care contacts for children with acute gastroenteritis. Parents were more likely to contact their primary care physician after hours when their child exhibited unusual behaviour, to prevent symptom deterioration, and to gain medical reassurances.
The researchers reported that parents expected their doctors to perform a thorough physical examination, provide information, and make follow-up care agreements. Parents reported dissatisfaction if they felt their doctors didn’t listen to them, misunderstood them, or didn’t take them seriously. This increased their likelihood of seeking another consultation. Researchers concluded that there is often a mismatch between parental expectations and GPs’ actions. Greater awareness and understanding on the part of GPs about the feelings and expectations of parents could guide them in interacting with parents, which may improve satisfaction with primary health care and reduce after-hours care requests.
The researchers found that among parents who requested out-of-office consultations for their children who were experiencing gastroenteritis, those that felt misunderstood or not listened to by their doctors were more likely to request such a visit. Taking greater account and understanding about parents’ feelings and expectations about care for their child may improve satisfaction with primary health care, specifically with requests that come in after normal clinic hours.
Positive results from a clinical trial comparing the safety and efficacy of ciclosporin with methotrexate in children and adolescents with severe dermatitis will likely change treatment paradigms for this debilitating skin condition, its researchers have said. The trial, published in the British Journal of Dermatology, also examined whether the severity of the disease changed or returned after treatment ended.
For children and young people with atopic dermatitis, the most common skin condition in children, the main first line conventional systemic treatments are methotrexate and ciclosporin, two immuno-modulatory drugs.
There have been no adequately powered randomised clinical trial evidence for safety and treatment success for paediatric patients with this condition, and with new therapies being introduced at a high cost, establishing a gold standard for treatment with the conventional systemic therapies like methotrexate and ciclosporin is needed.
The trial, led by King’s College London, assessed 103 children with severe atopic dermatitis age 2–16 years across 13 centres in the UK and Ireland. The patients were given oral doses of methotrexate or ciclosporin and assessed over nine months of treatment and six months after the therapy ended.
The study found that ciclosporin works faster and reduces disease severity more at 12 weeks but was more expensive, whereas methotrexate was significantly cheaper and led to better objective disease control after 12 weeks and off therapy, with fewer participant-reported flares of atopic dermatitis after treatment had stopped. There were also no concerning safety signals.
Based on the TREAT trial findings, methotrexate is a useful and safe treatment in paediatric patients with severe atopic dermatitis and a good alternative to ciclosporin, especially in settings where health care resources are limited.
Professor Carsten Flohr, Chair in Dermatology and Population Health Sciences at King’s College London, and consultant dermatologist at St John’s institute of dermatology, Guy’s and St Thomas’ NHS Foundation Trust, said:
“This is the largest paediatric trial using conventional immuno-modulatory treatments in severe atopic dermatitis and was conducted across 13 centres in the UK and Ireland and is likely to change our treatment paradigm around this condition, not just for patients in the UK but also internationally.”
A group of activists for food access and affordability met yesterday (Thursday 21 September 2023) to discuss the worsening food crisis for children. Convened by the Nelson Mandela Children’s Fund and the DG Murray Trust, the meeting sought to identify urgent measures to combat rising rates of severe acute malnutrition and child hunger.
The activist group includes representatives of COSATU, the South African Council of Churches, civil society groups and academics. It endorsed the proposal by the DG Murray Trust and the Grow Great Zero-Stunting Campaign for government and the food industry to contribute equally in making at least one product label of ten highly nutritious foods far more affordable to poorer households. This proposal requests food manufacturers and retailers to ‘double discount’ a list of ten best buy foods, with the amount of profit waived by industry matched by a retail subsidy by government.
“Data from the Department of Health shows that there were over 15 000 cases of severe acute malnutrition requiring hospitalisation in the 2022/3 financial year,” says Dr Linda Ncube Nkomo, CEO of the Nelson Mandela Children’s Fund. “But that is just the tip of the iceberg”, she says. “Malnutrition is the underlying cause of about one-third of all child deaths in South Africa today, this despite Section 28 of the Constitution which guarantees the right of nutrition to every child”.
The problem of acute malnutrition worsens the chronically high levels of food insecurity in South Africa, with over a quarter of children under five nutritionally stunted. Poor physical growth is just one manifestation of much deeper damage being done to the life-long wellbeing of children, not least to their brain development,” says Dr Edzani Mphaphuli, Executive Director of the Grow Great zero-stunting campaign. “If we don’t stop stunting now,” Mphaphuli continues, “we shouldn’t expect learning outcomes to improve or our economy to grow.”
In addition to the double-discounted basket of ten best buys, the group called on the food formula industry to stop extracting massive profits from the poorest mothers, whose own malnutrition makes breastfeeding difficult. Given the high cost of infant formula, desperate mothers water down the milk to make it stretch further, which means that their babies don’t get enough protein and vitamins. It also called on government to ensure that every province has an effective programme in place to identify children at high risk and to provide nutritional supplementation to children failing to thrive.
The group undertook to monitor food prices actively and to challenge the food industry to make the third of young children who live below the food poverty line their responsibility too. “We are heartened that NEDLAC has tasked a multi-sectoral committee to review the viability of proposal to double-discount ten best buy foods”, says Dr David Harrison, CEO of the DG Murray Trust. “No sector of society – not government, not labour, not civil society nor industry – should be able to say that substantive proposals to feed South Africa’s children are too difficult, without putting a better option on the table.”
Craniosynostosis, the premature fusion of the top of the skull in infants, is caused by an abnormal excess of a previously unknown type of bone-forming stem cell, according to a preclinical study published in Nature.
Occurring in one in 2500 babies, craniosynostosis arises from one of several possible gene mutations. By constricting brain growth, it can lead to abnormal brain development if not corrected surgically. In complex cases, multiple surgeries are needed.
Led by researchers at and led by researchers at Weill Cornell Medicine, the team focused on what happens in the skull of mice with one of the most common mutations found in human craniosynostosis. They found that the mutation drives premature skull fusion by inducing the abnormal proliferation of a type of bone-making stem cell, the DDR2+ stem cell, that had never been described before.
“We can now start to think about treating craniosynostosis not just with surgery but also by blocking this abnormal stem cell activity,” said study co-senior author Dr Matt Greenblatt, an associate professor of pathology and laboratory medicine at Weill Cornell Medicine and a pathologist at NewYork-Presbyterian/Weill Cornell Medical Center.
A new stem cell driving disorders of premature skull fusion was transplanted (red), showing that it makes the cartilage seen at sites of skull fusion (green). Credit: Greenblatt lab.
In a study published in Naturein 2018, Dr Greenblatt, study co-senior author Dr Shawon Debnath and their colleagues, described the discovery of a type of bone-forming stem cell they called the CTSK+ stem cell. Because this type of cell is present in the top of the skull, or “calvarium,” in mice, they suspected that it has a role in causing craniosynostosis.
For the new study, they knocked out genes associated with craniosynostosis in CSTK+ stem cells in mice. They expected that the gene deletion somehow would induce these calvarial stem cells to go into bone-making overdrive. This new bone would fuse the flexible, fibrous material called sutures in the skull that normally allow it to expand in infants.
“We were surprised to find that, instead of the mutation in CTSK+ stem cells leading to these stem cells being activated to fuse the bony plates in the skull as we expected, mutations in the CTSK+ stem cells instead led to the depletion of these stem cells at the sutures – and the greater the depletion, the more complete the fusion of the sutures,” Dr Debnath said.
The unexpected finding led the team to hypothesise that another type of bone-forming stem cell was driving the abnormal suture fusion. After further experiments, and a detailed analysis of the cells present at fusing sutures, they identified the culprit: the DDR2+ stem cell, whose daughter cells make bone using a different process than that utilised by CTSK+ cells.
The team found that CTSK+ stem cells normally suppress the production of the DDR2+ stem cells. But the craniosynostosis gene mutation causes the CTSK+ stem cells to die off, allowing the DDR2+ cells to proliferate abnormally.
Collaborating with other researchers, they found the human versions of DDR2+ stem cells and CTSK+ stem cells in calvarial samples from craniosynostosis surgeries—underscoring the likely clinical relevance of their findings in mice.
The findings suggest that inappropriate DDR2+ stem cell proliferation in the calvarium, in infants with craniosynostosis-linked gene mutations, could be treated by suppressing this stem cell population, through mimicking the methods that CTSK+ stem cells normally use to prevent expansion of DDR2+stem cells. The researchers found that the CTSK+ stem cells achieve this suppression by secreting a growth factor protein called IGF-1, and possibly other regulatory proteins.
“We observed that we could partly prevent calvarial fusion by injecting IGF-1 over the calvarium,” said study first author Dr Seoyeon Bok, a postdoctoral researcher in the Greenblatt laboratory.
“I can imagine DDR2+ stem cell-suppressing drug treatments being used along with surgical management, essentially to limit the number of surgeries needed or enhance outcomes,” Dr. Greenblatt said.
In addition to treatment-oriented research, he and his colleagues now are looking for other bone-forming stem cell populations in the skull.
“This work has uncovered much more complexity in the skull than we ever imagined, and we suspect the complexity doesn’t end with these two stem cell types,” Dr Greenblatt said.
Paediatric medicines often come in a sweetened liquid form for compliance in ingesting it, but if it’s too palatable, a child may empty an entire bottle and poison themselves. But children can perceive taste in different ways. A new study published in the International Journal of Molecular Sciences uncovers genetic variations in how sweetness of medicine is perceived, with adult participants of African descent finding it than those of European descent.
A multidisciplinary research group specialising in paediatrics, genetics, and psychophysics, co-led by Julie A. Mennella, PhD, Principal Investigator at the Monell Chemical Senses Center, has identified wide variation in the sensory perception of a paediatric formulation of ibuprofen. Some were tied to genetic ancestry, and some were not. These findings indicate that a range of factors come into play in determining how a medicine tastes to an individual. Their work is the first in a series of studies funded by the National Institutes of Health to look at variation in the taste of medicines.
“Taste is personal and determining how individuals differ and why is critical to understanding medication adherence and personal risks,” said Mennella. Bitter taste and irritating sensations in the throat are the top reasons for non-compliance, as a child (or adult) is less likely to ingest a medicine that is unpleasant (or tastes bad). However, if a child finds the medicine bottle uncapped and finds it tastes sweet like candy, they may ingest too much. Discovering how individuals differ in sensory perception is especially key when it comes to liquid ibuprofen, which accounts for many unintentional poison exposures among children younger than six years old in the US, according to the US Poison Centers.
“Sweetening medicines like ibuprofen is a delicate balance between having it taste good enough that kids take it, but bitter enough that, should they get unguarded access to it, it’s irritating enough that they stop drinking it and don’t poison themselves,” said Mennella. “We found genetic markers, both ancestry-related and independent of it, that could predict if someone would find a medication irritating or pleasantly sweet. If we get to the point of tailor-making medications in the future, knowing these associations could help us design taste specifically for each child in the not-so-distant future.”
The study included 154 adult panellists from Philadelphia, who represented the diversity of their city. According to a genome-wide association study, 63 had African ancestry, 51 European, 13 South Asian, seven East Asian, and seven American. They underwent training in sensory methods and then rated the sweetness, irritation, bitterness, and palatability of a paediatric formulation of a berry-flavoured ibuprofen after swallowing, and also after just tasting it without swallowing.
Researchers found that panellists of African genetic ancestry had fewer chemaesthetic sensations such as tingling or an urge to cough, rated the medicine as tasting sweeter and more palatable than those of European genetic ancestry. Researchers also found a novel association between the TRPA1rs1198875 genetic variation and tingling sensations, independent of ancestry. This is significant as TRPA1 is a family of neuron receptors that are involved in sensory neural response to a variety of chemical irritants found in foodstuff and other medicines.
Discovering both an ancestry-related link and non-ancestry-related genetic variation to taste and irritation perception shows that who perceives a medicine as palatable or not is a complicated picture and must consider a variety of factors.
This first study was conducted with adults because the sensory measures were complex and included several hour-long test sessions. That does not mean future tests should not include children, Mennella said, adding that this is just the first in a line of studies on the taste of paediatric medicines and methods need to be developed to measure sensory irritation in children. “This is a small study, but it is the first step in showing how research on diverse populations is needed to be able to unravel the genetic, cultural, dietary, and developmental paths that underlie medicine adherence and also risk for poisoning,” said Mennella. “It’s looking at both sides of the same, very important coin.”
Findings from this research will affect how sensory tests can be designed in the future. Since participants did both swallow and sip-and-spit tests, the team was able to determine that just tasting medicine allowed predictions and perceptions after swallowing, which could simplify future studies in different age groups. Other studies as part of this National Institutes of Health grant are ongoing, including determining the variation and acceptance of medicines in children.
In a new study published in Pediatrics, researchers investigated the characteristics and trends of out-of-hospital attention-deficit/hyperactivity disorder (ADHD) medication errors among children and teenagers reported to US poison centres from 2000 through 2021. Their results showed that the number of medication errors increased by nearly 300%, with over half resulting from an accidental double dosage.
ADHD is among the most common paediatric neurodevelopmental disorders. In 2019, nearly 10% of children in the US had a diagnosis of ADHD, roughly half of whom currently have a prescription for ADHD medication.
According to the study by at the Center for Injury Research and Policy and Central Ohio Poison Center at Nationwide Children’s Hospital, the annual number of ADHD-related medication errors increased 299% from 2000 to 2021. During the study period, there were 87 691 medication error cases involving ADHD medications as the primary substance among this age group reported to poison centres, yielding an average of 3985 individuals annually. In 2021 alone, 5235 medication errors were reported. The overall trend was driven by males, accounting for 76% of the medication errors and by the 6–12-year-old age group, accounting for 67% of the errors. Approximately 93% of exposures occurred in the home.
Among medication errors involving ADHD medications as the primary substance, the most common scenarios were:
“The increase in the reported number of medication errors is consistent with the findings of other studies reporting an increase in the diagnosis of ADHD among US children during the past two decades, which is likely associated with an increase in the use of ADHD medications,” said Natalie Rine, PharmD, co-author of the study and director of the Central Ohio Poison Center at Nationwide Children’s Hospital.
In 83% of cases, the individual did not receive treatment in a health care facility; however, 2.3% of cases resulted in admission to a health care facility, including 0.8% to a critical care unit. In addition, 4.2% of cases were associated with a serious medical outcome. Some children experienced agitation, tremors, seizures, and changes in mental status. Children under age 6 were twice as likely to experience a serious medical outcome and were more than three times as likely to be admitted to a health care facility than 6–19-year-olds.
“Because ADHD medication errors are preventable, more attention should be given to patient and caregiver education and development of improved child-resistant medication dispensing and tracking systems,” said Gary Smith, MD, DrPH, senior author of the study and director of the Center for Injury Research and Policy at Nationwide Children’s Hospital. “Another strategy may be a transition from pill bottles to unit-dose packaging, like blister packs, which may aid in remembering whether a medication has already been taken or given.”
Although prevention efforts should focus on the home setting additional attention should be given to schools and other settings where children and adolescents spend time and receive medication.
Breastfeeding in infancy has been shown to confer cognitive and health benefits. For decades, researchers have sought to create a viable complement or alternative to breast milk to give children their best start for healthy development. New research out of the University of Kansas and published in the Journal of Pediatrics has shown how a complex component of milk that can be added to infant formula has been shown to confer long-term cognitive benefits, including measures of intelligence and executive function in children.
The research by John Colombo, KU Life Span Institute director and investigator, along with colleagues at Mead Johnson Nutrition and in Shanghai, China, adds to the growing scientific support for the importance of ingredients found in milk fat globule membrane (MFGM) in early human development.
The study showed that feeding infants formula supplemented with MFGM and lactoferrin for 12 months raised IQ by 5 points at 5 ½ years of age. The effects were most evident in tests of children’s speed of processing information and visual-spatial skills. Significant differences were also seen in children’s performance on tests of executive function, which are complex skills involving rule learning and inhibition.
All forms of mammalian milk contain large fat globules that are surrounded by a membrane composed of a variety of nutrients important to human nutrition and brain development, Colombo said. When milk-based infant formula is manufactured, the membrane has typically been removed during processing.
“No one thought much about this membrane,” Colombo said, “until chemical analyses showed that it’s remarkably complex and full of components that potentially contribute to health and brain development.”
The 2023 study was a follow-up to a 2019 one also published in the Journal of Pediatrics, which showed that babies who were fed formula with added bovine MFGM and lactoferrin had higher scores on neurodevelopmental tests during the first year and on some aspects of language at 18 months of age.
The global nutrition research community has been looking at MFGM for about a decade, Colombo said. Because the membrane is made up of several different components, it isn’t known whether one of the components is responsible for these benefits, or whether the entire package of nutrients act together to improve brain and behavioural development.
These benefits were seen in children long after the end of formula feeding at 12 months of age.
“This is consistent with the idea that early exposure to these nutritional components contribute to the long-term structure and function of the brain,” said Colombo, who has spent much of his career researching the importance of early experience in shaping later development.
Several major childhood allergies may all stem from the gut microbiome gut, according to a new study published in Nature Communications. The research identifies gut microbiome features and early life influences that are associated with children developing any of four common allergies. The study, led by researchers at the University of British Columbia and BC Children’s Hospital, could lead to methods of predicting whether a child will develop allergies, and methods to prevent their development.
“We’re seeing more and more children and families seeking help at the emergency department due to allergies,” said Dr Stuart Turvey, paediatrics professor at UBC and co-senior author on the study, noting that as many as one in three children in Canada have allergies.
The study is one of the first to examine four distinct school-aged paediatric allergies at once: atopic dermatitis, asthma, food allergy and allergic rhinitis. While these allergic diseases each have unique symptoms, the Turvey lab was curious whether they might have a common origin linked to the infant gut microbiota composition.
“These are technically different diagnoses, each with their own list of symptoms, so most researchers tend to study them individually,” says Dr Charisse Petersen, co-senior author on the paper and postdoctoral fellow in the Turvey lab. “But when you look at what is going wrong at a cellular level, they actually have a lot in common.”
For the study, researchers examined clinical assessments from 1115 children who were tracked from birth to age five. Roughly half of the children (523) had no evidence of allergies at any time, while more than half (592) were diagnosed with one or more allergic disorders by an expert physician. The researchers evaluated the children’s microbiomes from stool samples collected at clinical visits at three months and one year of age.
The stool samples revealed a bacterial signature that was associated with the children developing any of the four allergies by five years of age. The bacterial signature is a hallmark of dysbiosis, or an imbalanced gut microbiota, that likely resulted in a compromised intestinal lining and an elevated inflammatory response within the gut.
“Typically, our bodies tolerate the millions of bacteria living in our guts because they do so many good things for our health. Some of the ways we tolerate them are by keeping a strong barrier between them and our immune cells and by limiting inflammatory signals that would call those immune cells into action,” says Courtney Hoskinson, a PhD candidate at UBC and first author on the paper. “We found a common breakdown in these mechanisms in babies prior to the development of allergies.”
Many factors can shape the infant gut microbiota, including diet, place and delivery method of birth and antibiotics exposure. The researchers examined how these types of influences affected the balance of gut microbiota and the development of allergies.
“There are a lot of potential insights from this robust analysis,” says Dr Turvey. “From these data we can see that factors such as antibiotic usage in the first year of life are more likely to result in later allergic disorders, while breastfeeding for the first six months is protective. This was universal to all the allergic disorders we studied.”
Now the researchers hope to leverage the findings to inform treatments that correct an imbalanced gut microbiota and could potentially prevent allergies from developing.
“Developing therapies that change these interactions during infancy may therefore prevent the development of all sorts of allergic diseases in childhood, which often last a lifetime,” says Dr Turvey.
Hours of inactivity during childhood could be setting the stage for heart attacks and strokes later in life, according to research presented at ESC Congress 2023. The large cohort study found that sedentary time accumulated from childhood to young adulthood was associated with heart damage – even in those with normal weight and blood pressure.
“All those hours of screen time in young people add up to a heavier heart, which we know from studies in adults raises the likelihood of heart attack and stroke,” said study author Dr Andrew Agbaje of the University of Eastern Finland, Kuopio, Finland. “Children and teenagers need to move more to protect their long-term health.”
This was the first study to investigate the cumulative effect of smartwatch-assessed sedentary time in young people and cardiac damage later in life. It was conducted as part of the Children of the 90s study, which began in 1990/1991 and is one of the world’s largest cohorts with lifestyle measurements from birth.
At 11 years of age, children wore a smartwatch with an activity tracker for seven days. This was repeated at 15 years of age and again at 24 years of age. The weight of the heart’s left ventricle was assessed by echocardiography, a type of ultrasound scan, at 17 and 24 years of age and reported in grams relative to height (g/m2.7). The researchers analysed the association between sedentary time between 11 and 24 years of age and heart measurements between 17 and 24 years of age after adjusting for factors that could influence the relationship including age, sex, blood pressure, body fat, smoking, physical activity and socioeconomic status.
The study included 766 children, of whom 55% were girls and 45% were boys. At 11 years of age, children were sedentary for an average of 362 minutes a day, rising to 474 minutes a day in adolescence (15 years of age), and 531 minutes a day in young adulthood (24 years of age). This means that sedentary time increased by an average of 169 minutes (2.8 hours) a day between childhood and young adulthood.
Each one-minute increase in sedentary time from 11 to 24 years of age was associated with a 0.004g/m2.7 increase in left ventricular mass between 17 to 24 years of age. When multiplied by 169 minutes of additional inactivity this equates to a 0.7g/m2.7 daily rise, the equivalent of a 3 gram increase in left ventricular mass between echocardiography measurements at the average height gain. A previous study in adults found that a similar increase in left ventricular mass (1g/m2.7) over a seven-year period was associated with a two-fold increased risk of heart disease, stroke, and death.4
Dr. Agbaje said: “Children were sedentary for more than six hours a day and this increased by nearly three hours a day by the time they reached young adulthood. Our study indicates that the accumulation of inactive time is related to heart damage regardless of body weight and blood pressure. Parents should encourage children and teenagers to move more by taking them out for a walk and limiting time spent on social media and video games. As Martin Luther King Jr. once said, ‘If you can’t fly, run. If you can’t run, walk. If you can’t walk, crawl. But by all means keep moving.'”
This illustration depicted a three-dimensional (3D), computer-generated image, of a group of Gram-positive, Streptococcus pneumoniae bacteria. The artistic recreation was based upon scanning electron microscopic (SEM) imagery.
Doctors typically treat paediatric ear infections with antibiotics, but children don’t always complete the full course, accelerating resistance to these medications. Today, researchers report developing a single-use nanoscale system that’s unlikely to generate resistance. Using a compound similar to bleach in test animals, they show it can kill off Streptococcus pneumoniae, a common cause of ear infections, and it could someday be easily applied as a gel.
The researchers will present their results at the meeting of the American Chemical Society (ACS).
“We initially conceived of this idea by looking at the household cleaner bleach. Even though it has been used since the 19th century, bacteria do not appear to have developed any widespread resistance to this cleaner,” says Rong Yang, PhD, the project’s principal investigator.
But Yang quickly warns that people should not treat infections with bleach. The solution sold at stores is highly concentrated and caustic, but when used in a properly controlled manner at extremely low concentrations, the active ingredient in bleach is considered compatible with living tissue.
After realising that the active ingredient in the household cleaner could circumvent antibiotic resistance, the Cornell University researchers, set out to tackle a nearly universal childhood scourge: acute ear infections. These infections affect more than 95% of children in the US, and treatment typically requires taking antibiotics for five to 10 days. However, these regimens can cause problematic side effects, leading some families to discontinue the medication prematurely, particularly if symptoms resolve. But using these medications improperly can speed up the development of antibiotic resistance, which makes infections more difficult, if not impossible, to treat. This issue ranks among the biggest threats to global health, according to the World Health Organization.
Bacteria have more success fighting against some substances than others. Hypochloric acid from bleach belongs to a family of compounds, known as hypohalous acids, to which bacteria have yet to develop any significant resistance; most likely because of the numerous ways these highly reactive acids damage microbial cells, Yang says.
Because these substances break down quickly, Yang and her colleagues sought to generate one of them on an as-needed basis behind the eardrum in the middle ear, where ear infections occur. They found inspiration in an enzyme from giant kelp, which converts hydrogen peroxide (H2O2) to hypobromous acid (HOBr), a chemical relative of bleach.
Streptococcus pneumoniae, a frequent cause of ear infections, produces H2O2 to fight off other microbes. To mimic the kelp enzyme, which contains the metal vanadium, Yang and her colleagues designed nanowires made of vanadium pentoxide (V2O5). These produce HOBr only in the presence of the H2O2-producing bacteria, and their rod-like shape helps to keep them in place by reducing their ability to diffuse into body fluids.
In tests on chinchillas, which contract ear infections from the same pathogens as human children, they succeeded in eliminating most of the S. pneumoniae. Yang and colleagues found that after treatment with the nanowires, the animals’ once-inflamed eardrums returned to normal. Meanwhile, tests in healthy animals found evidence that the treatment did not interfere with hearing.
For these experiments, the researchers injected the nanowires directly into the middle ear. In more recent work in chinchillas, they developed a less invasive, more practical method for delivering the wires. By decorating the nanowires with peptides known to transport small particles across the eardrum, Yang and her team found they could deliver the treatment topically as a gel deposited into the ear canal. Once the gel was applied, the nanowires within it went through the intact tissue. They are also exploring other approaches for passing the nanowires through the eardrum.
Because other ear-infection-causing bacteria do not produce H2O2, the researchers are currently examining whether this system is effective in the presence of microbes other than S. pneumoniae, and how they might adapt it to fight the other bugs.
The researchers have not yet done studies to determine how long the system stays in place, although their evidence suggests the nanowires drain out of the middle ear after the infection clears. However, Yang suspects they could adapt the nanowires’ properties to stay in place for long periods afterward. This latter approach could make it possible to prevent recurrent infections that plague many children.
“If the bacteria return, the system could restart, so children wouldn’t need antibiotics repeatedly and breed more resistance along the way,” Yang says.
