An unexpectedly high percentage of children, who were born with HIV and started treatment within 48 hours of life, exhibit biomarkers by two years of age that may make them eligible to test for medication-free remission, according to a multinational study published in The Lancet HIV.
“Moving away from reliance on daily antiretroviral therapy (ART) to control HIV would be a huge improvement to the quality of life of these children,” said Protocol Co-Chair and senior author Ellen Chadwick, MD, at Ann & Robert H. Lurie Children’s Hospital.
Conducted in 11 countries including South Africa, the proof-of-concept study was charged with replicating the case of HIV remission as seen in the “Mississippi baby” that was reported in 2013. In that case, the infant started ART at 30 hours of life, was treated for 18 months, and achieved 27 months of ART-free remission before the virus rebounded. Typically, if ART is stopped, the virus rebounds within a month.
The study included a three-drug ART regimen initiated within 48 hours of life, with the fourth drug added within 2-4 weeks. This is very early treatment compared to the standard of care where three-drug ART may not begin until 2-3 months of age.
In the US, however, based on earlier findings from this study, very early treatment is now the norm for infants at high risk of acquiring HIV infection from their mother.
“With earlier treatment, we hope to limit or prevent the establishment of viral reservoirs in the body. These viral reservoirs hold small amounts of hidden virus which are hard to reach with ART. By shrinking these reservoirs, we expect to increase the amount of time that patients can be in remission, without needing daily ART,” said co-author and Protocol Co-Chair Jennifer Jao, MD, MPH, from Lurie Children’s.
Dr Chadwick adds: “Another benefit of smaller viral reservoirs might be that newer treatments such as long-acting antibody therapies or therapeutic vaccines could potentially be used instead of daily ART.”
“Our results show a higher percentage of children might be eligible to interrupt therapy than we expected, and the next step is to stop ART and see how many children actually achieve remission,” said Dr Chadwick.
“If even one child achieves remission, that would be considered a success. Today, newer more effective and better tolerated HIV medications are available for infants than when the study began, strengthening the prospect of limiting viral reservoirs and testing for possible remission in infants and children with HIV. Overall, this is an exciting advancement and an opportunity to change the course of pediatric HIV infection.”
The study was conducted in 11 countries – Brazil, Haiti, Kenya, Malawi, South Africa, Tanzania, Thailand, Uganda, USA, Zambia and Zimbabwe.
A major clinical trial has found that vitamin D supplements do not increase bone strength or prevent bone fractures in children with vitamin D deficiency. The findings, published in Lancet Diabetes & Endocrinology, challenge widely held perceptions relating to the effects of vitamin D on bone health.
Around one-third of children have at least one fracture before the age of 18. This is a major global health issue, as childhood fractures can lead to life years of disability and/or poor quality of life. The potential for vitamin D supplements to improve bone strength has attracted growing interest in recent years, based on vitamin D’s role in promoting bone mineralisation. But there have been no clinical trials to test whether vitamin D supplements can prevent bone fractures in children.
Working with partners in Mongolia, a setting with a particularly high fracture burden and where vitamin D deficiency is highly prevalent, researchers from led by Queen Mary University of London and the Harvard T.H. Chan School of Public Health conducted a clinical trial to determine if vitamin D supplementation would decrease risk of bone fractures or increase bone strength in schoolchildren.
This study is also the largest randomised controlled trial of vitamin D supplementation ever conducted in children. Over the course of three years, 8851 schoolchildren aged 6-13 living in Mongolia received a weekly oral dose of vitamin D supplementation.
Testing revealed that 95.5% of participants had vitamin D deficiency at baseline, and study supplements were highly effective in boosting vitamin D levels into the normal range. No effect was seen on fracture risk or on bone strength, measured in a subset of 1438 participants using quantitative ultrasound.
The trial findings are likely to prompt scientists, doctors and public health specialists to re-consider the effects of vitamin D supplements on bone health.
Dr Ganmaa Davaasambuu, Associate Professor at the Harvard T.H. Chan School of Public Health, said:
“The absence of any effect of sustained, generous vitamin D supplementation on fracture risk or bone strength in vitamin D deficient children is striking. In adults, vitamin D supplementation works best for fracture prevention when calcium is given at the same time – so the fact that we did not offer calcium alongside vitamin D to trial participants may explain the null findings from this study.”
Professor Adrian Martineau, Lead of the Centre for Immunobiology at Queen Mary University of London, added:
“It is also important to note that children who were found to have rickets during screening for the trial were excluded from participation, as it would not have been ethical to offer them placebo (dummy medication). Thus, our findings only have relevance for children with low vitamin D status who have not developed bone complications. The importance of adequate vitamin D intake for prevention of rickets should not be ignored, and UK government guidance recommending a daily intake of 400 IU vitamin D remains important and should still be followed.”
For decades, the standard way to prevent people who were exposed to tuberculosis (TB) from falling ill with the disease was to offer them a medicine called isoniazid, taken daily for six or more months. That changed in the last decade with the development of new preventive therapy regimens that are taken for four, three, or even just one month.
One complexity, however, is that both isoniazid and the new regimens are much better at preventing normal drug-sensitive TB than they are at preventing drug-resistant forms of TB. This is not surprising. As explained by Paediatric Infectious Disease doctor and Professor of Global Child Health at Imperial College London, Dr James Seddon, the two drugs that have mainly been used to prevent drug-susceptible TB are isoniazid and rifampicin (rifampicin’s sister drug rifapentine is also used). Now, by definition, he explains multidrug-resistant (MDR) TB is resistant to both these drugs so it’s unlikely to have any impact.
The situation is particularly tricky when it comes to children. In a 2020 statement the World Health Organization (WHO) says that it estimated that worldwide between 25 000 and 32 000 children develop MDR-TB each year, and mainly acquire it through transmission from close contact with an adult or adolescent who has MDR-TB. According to Seddon, while there is some emerging observational evidence on the use of drugs other than isoniazid and rifampicin to prevent MDR-TB, there has been no clinically tested regimen to give to children following MDR-TB exposure.
Now, much anticipated results from a phase three trial has shown that a single antibiotic pill, given daily for six months, is safe and effective to use in children who have been exposed to MDR-TB.
Results from TB CHAMP
The trial, called TB-CHAMP, looked at the efficacy and safety of using the antibiotic levofloxacin to prevent TB in children exposed to MDR-TB. Top-line findings from the study was presented last week at the Union World Lung Conference held in Paris, France.
“The paediatric population is probably the most neglected of all the populations affected by MDR-TB,” Dr Anneke Hesseling, Director of the Paediatric TB Research Programme at Stellenbosch University, told the conference. “Fewer than 20% who develop MDR-TB disease are actually diagnosed and treated, and so to find more cases and prevent more cases is really, really critical…So prevention is really key, and the TB-CHAMP trial is really a phase three efficacy trial looking at levofloxacin to prevent new cases of TB in children and also looking at the safety of levofloxacin.”
Hesseling, who is the Principal Investigator of the study, says that TB-CHAMP is the first trial to provide clinical data on what drug might be used to prevent TB in children who have been exposed to MDR-TB. It was conducted at five sites across South Africa, all with high MDR-TB burdens. The study was led by Stellenbosch University and the Desmund Tutu TB Centre. The findings have not yet been published in a peer-reviewed journal.
922 children were randomised to receive either levofloxacin or a placebo for six months. 453 children got levofloxacin and 469 got the placebo. The primary efficacy data featured data from 916 of those children, with 451 in the levofloxacin arm and 465 in the placebo arm.
Hesseling says that only children who were exposed to an adult in their household with confirmed MDR-TB were included in the study. At first children below the age of five were recruited, regardless of their TB infection status. Later children between the ages of five and 17 were included, but they had to either have a TB infection or be living with HIV. The majority of the children, 90%, were younger than five years. TB infection was confirmed with a blood test.
By 48 weeks, Hesseling says five children in the levofloxacin arm versus 12 in the placebo arm developed TB, which amounts to an incidence rate of 1.1% in the levofloxacin arm, and 2.6% in the placebo arm.
Implication of results
“While TB preventive therapy (TPT) has long been recommended and available for young child contacts of people with drug-susceptible TB, there has not been sufficient evidence to make strong recommendations for treatment that could prevent DR-TB. Therefore, the TB-CHAMP findings are critically important for a number of reasons,” says Professor Guy Marks, President and Interim Executive Director, International Union Against Tuberculosis and Lung Disease (The Union).
“The study provides the first high-quality evidence that DR-TB can be prevented in children by using six months of daily levofloxacin, and that this is a safe medication. Furthermore, this will encourage more community-based contact screening, which will also lead to early detection of children and contacts of all ages who already have disease, and initiate treatment,” he adds.
“The impact [of the TB-CHAMP results] is potentially tremendous as it would prevent DR TB among child contacts. DR TB is more complex to treat and cure and often children are marginalised, so this study puts the spotlight on an effective way to protect children. This is not just about the life and health of the child but the social, economic and mental health implications for the caregiver and the entire family,” says Dr Priashni Subrayen, Technical Director for TB at The Aurum Institute.
Seddon, who is also one of the Co-PIs for the study, tells Spotlight that it was important to establish the safety of levofloxacin since it belongs to a class of drugs called the fluoroquinolones, which were thought to have terrible side effects when used in children.
Results from TB-CHAMP show that this is not the case.
The side effects were mild, and the regimen was well tolerated, according to Hesseling, with only eight children having a grade one or higher adverse event in the levofloxacin arm compared to four in the placebo arm. Two deaths were reported, one in each study arm, but were unrelated to the study. Overall, six children in the levofloxacin arm discontinued treatment or left the study early.
Researchers from TB-CHAMP collaborated with researchers from the V-QUIN trial – a phase three study that looked at levofloxacin as TB prevention in adults in Vietnam – in order to combine their data which allowed them to show data for levofloxacin across different age groups. Seddon explains: “They’ve applied a novel analytic approach, which uses a Bayesian, or probabilistic, framework, where we take the results of TB-CHAMP and we say well, if we actually use some of the information from V-QUIN to inform the TB-CHAMP results, we can make that a slightly more confident estimate,” he says.
The combined results, according to Hesseling were able to also show that levofloxacin reduced the risk of TB by about 60% across the age spectrum but with a tighter confidence interval, indicating a more precise estimate of the effect.
Seddon tells Spotlight that the combined data showed that there were no serious adverse events, but the adult population experienced more grade one and grade two side effects than the children, but these went away either over time or when the drug was stopped. The side effects included inflammation in the joints and tendons, which is a known side effect of this class of drug.
Not a silver bullet
While the findings could be a game-changer and potentially inform MDR-TB prevention guidelines, particularly in children, the regimen is by no means a silver bullet. Seddon says that while the regimen was safe, when participants were asked whether they liked the medicine, more people said they didn’t like it in the levofloxacin group versus the placebo. Another downside is that the pill was an adult formulation and thus needed to be cut and/or crushed for the kids to swallow.
Seddon explains that the WHO, who have been provided with the data from both studies and expected to meet in early December, would need to consider a variety of factors before deciding what to recommend about the use of levofloxacin for prevention. That includes the fact that you need to treat a lot of children for six months who might not have TB despite being exposed in order to prevent a few cases.
“You have to weigh up the benefits versus the risks and the risks are low, but it is still giving a drug for six months to children and most of them don’t need it. But the consequences of getting MDR-TB are so bad that we really want to prevent that,” he says.
There is also the question around what effect using a broad antibiotic as preventive treatment will have on the microbiome of children and how this might drive resistance to the fluoroquinolones. Seddon says stool samples were collected from the study participants to determine how the drug affected a child’s microbiome and the potential for driving resistance. These data will also be provided to the WHO.
“I think that the evidence base is now very strong on the basis of these two trials. I think you can really say the issue of whether levofloxacin prevents MDR-TB, we’ve put that to bed,” he says. “Are there going to be other studies? Yes. I think that this is not over, levofloxacin is not the perfect drug for preventive therapy.”
Marks adds to this saying: “An important next step for TPT in DR-TB contacts will be studies that evaluate regimens that are shorter than six months – a long time to take medication every day, which can often be challenging. Effective and safe shorter regimens are now being used for child contacts of drug-susceptible TB and we hope the same progress can be made for contacts of DR-TB.”
As Marks has already stated, currently there are no strong recommendations for MDR-TB prevention by the WHO. In the 2020 TB prevention guidelines, it recommends that the preventative treatment for MDR-TB should be either a fluroquinolone or other second-line agent. It does however caution that these recommendations are based on low-quality evidence. Because of this, it recommends that the preventative treatment for MDR-TB should be individualised, and it be based on the drug resistance profile of the presumed contact. The drugs levofloxacin and moxifloxacin- both fluoroquinolones – may be used unless resistance is suspected. For levofloxacin a dosing schedule for both adults and children are proposed in the document.
Subrayen says that in South Africa the 2019 guidelines for the management of Rifampicin Resistant-TB (RR-TB) does indicate the use of levofloxacin as prevention treatment. The guidelines state that for prevention treatment a fluoroquinolone-based, multidrug regimen is preferred (either levofloxacin and high-dose isoniazid or levofloxacin, high-dose isoniazid and ethambutol). And if exposed to fluoroquinolone-resistant RR-TB, then high-dose isoniazid could be given. Delamanid could be considered as a potential option in very select cases. A training manual published this year by the Department of Health suggests that levofloxacin can be given on its own – but also stresses that the evidence base is weak, something that TB-CHAMP has presumably now changed.
Future of TPT
Seddon says that in a perfect world the ideal TB preventive regimen would be a so-called Pan regimen that could be given for a short period of time, to someone who has been exposed to TB and it works regardless of whether they had been exposed to drug-susceptible or drug-resistant TB.
“There are studies planned to use other drugs for prevention. There’s a study planned to use bedaquiline for a month or two and potentially using injectables that you just have to give once every couple of weeks. So, I think although this [levofloxacin] is a good option now, and it’s probably the best option we have now, this is not perfect,” Seddon says.
The study Seddon is referring to is the BREACH-TB study, a phase three trial that will look at whether a one-month treatment regimen of oral bedaquiline could prevent all forms of tuberculosis. It would be given to people exposed to both drug-resistant and drug-susceptible TB, and in people with HIV infection, including pregnant women and children.
Responding to questions from Spotlight earlier this year when this study was announced in the press, Sonya Krishnan, Assistant Professor of Medicine at Johns Hopkins University and Eric Nuermberger, Professor of Medicine at Johns Hopkins University, said that they anticipate recruiting between 1600 and 2 00 people to take part in the study – they expect around 400 to 500 of these will be people living with HIV. They also said that the control arm will receive the current standard of care in the country rather than placebo.
When asked whether any South African study sites will be included in the clinical trial, they said, “We very much plan to partner with study sites in South Africa. South Africa has a long-standing history of research excellence in TB.”
“A shorter regimen that fights both drug-resistant and drug-susceptible TB would be a game-changer for those living with TB and get us closer to our shared goal of ending the epidemic by 2030,” said Dr. Atul Gawande, USAID assistant administrator for Global Health, in a statement on the study. “This clinical trial will lay the foundation for a remarkable innovation in our fight against TB: a single-dose, long-acting injectable medicine.”
Indeed, if the science and development pans out as Gawande suggests it might, the future of TB preventive therapy might well be an entire course of therapy delivered through a single injection rather than a month or more of pills. As indicated in an article in the journal Clinical Infectious Diseases, work is already underway on the development of bedaquline, isoniazid, and rifapentine long-acting injections – though the research is for now still only in mice.
‘Communities need to be involved’
Hesseling raises the point that when treating or preventing TB, more than just the latest research advancement is needed to improve TB outcomes.
“For me treatment follows diagnosis, actually strengthening healthcare services, making communities more aware and creating demand for kids accessing diagnosis, preventive treatment and appropriate treatment, is actually where it starts,” she says. “So tools are amazing, but we actually need to have strong, effective healthcare services and knowledgeable, empowered communities.”
Seddon adds to this saying that results like those from TB-CHAMP are “a bit irrelevant if it is all kind of top down, paternalistic coming from the researchers, coming from the health system”.
“We really need to generate a community demand for this, where individuals living in communities where this is a problem are calling for this and getting angry about this and demanding it in a way that I think we’ve achieved very well with the HIV community,” he says. “It’s all well and good doing the science and then even better to get it [levofloxacin] into a guideline, but until there’s real demand for from the end user, I think it’s only going to have a certain amount of reach.”
Note: The terms DR-TB and MDR-TB are used somewhat interchangeably – Spotlight uses DR-TB to refer to drug-resistant forms of TB in general and MDR-TB to refer specifically to TB that is resistant to isoniazid and rifampicin.
A treatment to move blood from the umbilical cord into an infant’s body may provide a safe option for preterm infants born after 28 weeks who need rapid support, suggests a study supported by the National Institutes of Health. The procedure, called umbilical cord milking, involves gently squeezing the cord between the thumb and forefinger and pushing the blood into the newborn’s abdomen.
The new findings suggest that concerns raised by a 2019 study of infants born before 28 weeks (which concluded that umbilical cord milking might increase the risk of bleeding inside the brain) do not apply to preterm infants born after 28 weeks. The current study appears in Pediatrics.
The standard procedure, delaying cord clamping while blood naturally flows into the infant’s body, takes 30 to 180 seconds. However, cord milking, takes about 20 seconds, reducing delay for infants who need immediate assistance, such as respiratory support. Both procedures allow for umbilical cord blood to reach the infant’s body before clamping, reducing the risk of anaemia and other complications seen among infants receiving immediate cord clamping and cutting.
The study was conducted by Anup Katheria, M.D., of the Sharp Mary Birch Hospital for Women & Newborns in San Diego, and colleagues in the United States, Canada and Europe. It was supported by NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development.
More than 1000 infants were randomly assigned either to umbilical cord milking or delayed cord clamping. Rates of severe intraventricular haemorrhage and/or death did not differ significantly between the two groups (just over 1%). Moreover, the rates of overall intraventricular haemorrhage were also similar between the groups (approximately 12%). The researchers will follow all the infants in the study for two years to observe longer term outcomes.
High rates of antibiotic resistance now meant that drugs to treat common infections in children and babies are no longer effective in large parts of the world, according to findings published in Lancet South East Asia.
The University of Sydney led study found many antibiotics recommended by the World Health Organization (WHO) had less than 50% effectiveness in treating childhood infections such as pneumonia, sepsis (bloodstream infections) and meningitis. The findings show global guidelines on antibiotic use are outdated and need updates.
The most seriously affected regions are in South-East Asia and the Pacific, including neighbouring Indonesia and the Philippines, where thousands of unnecessary deaths in children resulting from antibiotic resistance occur each year.
The WHO has declared antimicrobial resistance (AMR) is one of the top 10 global public health threats facing humanity. In newborns, an estimated three million cases of sepsis occur globally each year, with up to 570 000 deaths: many of these are due to lack of effective antibiotics to treat resistant bacteria.
The findings add to mounting evidence that common bacteria responsible for sepsis and meningitis in children are often resistant to prescribed antibiotics.
The research reveals the urgent need for global antibiotic guidelines to be updated, to reflect the rapidly evolving rates of AMR. The most recent guideline from The World Health Organization was published in 2013.
The study found one antibiotic in particular, ceftriaxone, was likely to be effective in treating only one in three cases of sepsis or meningitis in newborn babies. Ceftriaxone is also widely used in Australia to treat many infections in children, such as pneumonia and urinary tract infections.
Another antibiotic, gentamicin, was found likely to be effective in treating fewer than half of all sepsis and meningitis cases in children.
Gentamicin is commonly prescribed alongside aminopenicillins, which the study showed also has low effectiveness in combating bloodstream infections in babies and children.
Lead author Dr Phoebe Williams from the University’s School of Public Health and Sydney Infectious Diseases Institute is an infectious disease specialist whose research focuses on reducing AMR in high-burden healthcare settings in Southeast Asia.
She also works as a clinician in Australia. Dr Williams says there are increasing cases of multidrug-resistant bacterial infections in children around the world.
AMR is more problematic for children than adults, as new antibiotics are less likely to be trialled on, and made available to, children.
Dr Williams says the study should be a wake-up call for the whole world, including Australia.
“We are not immune to this problem – the burden of anti-microbial resistance is on our doorstep,” she said.
“Antibiotic resistance is rising more rapidly than we realise. We urgently need new solutions to stop invasive multidrug-resistant infections and the needless deaths of thousands of children each year.”
The study analysed 6,648 bacterial isolates from 11 countries across 86 publications to review antibiotic susceptibility for common bacteria causing childhood infections.
Dr Wiliams said the best way to tackle antibiotic resistance in childhood infections is to make funding to investigate new antibiotic treatments for children and newborns a priority.
“Antibiotic clinical focus on adults and too often children and newborns are left out. That means we have very limited options and data for new treatments.”
Dr Williams is currently looking into an old antibiotic, fosfomycin, as a temporary lifeline to treat multidrug-resistant urinary tract infections in children in Australia.
She is also working with the WHO’s Paediatric Drug Optimisation Committee to ensure children have access to antibiotics to treat multidrug-resistant infections as soon as possible, to reduce deaths due to AMR among children.
“This study reveals important problems regarding the availability of effective antibiotics to treat serious infections in children,” says senior author Paul Turner, director of the Cambodia Oxford Medical Research Unit at Angkor Hospital for Children, Siem Reap and professor of paediatric microbiology at the University of Oxford, UK.
“It also highlights the ongoing need for high quality laboratory data to monitor the AMR situation, which will facilitate timely changes to be made to treatment guidelines.”
Children fall broadly into four eating categories, according to new research at Aston University, and parents feed their children differently depending on those categories.
The four categories identified by Dr Abigail Pickard and the team in the School of Psychology are ‘avid’, ‘happy’, ‘typical’, and ‘fussy’. The results, which showed specific temperaments and carer feeding patterns associated with overeating, are published in the journal Appetite.
In the UK, around a fifth of children are overweight or obese when they begin school, rising to around a third by the time they leave primary school at age 11. The team sought to identify eating behaviour patterns and how these are associated with temperament, feeding practices and food insecurity, as a way to predict which children are more at risk of becoming overweight.
Typical eaters made up 44% of the children in the study, while fussy eaters accounted for 16%. But of greatest interest to the team was that around one in five young children in the study were found to show “avid eating,” including greater enjoyment of food, faster eating speed, and weaker sensitivity to internal cues of ‘fullness’. The behaviours that distinguish children with avid eating from those who show ‘happy’ eating (17.7% of children in the study), who have similarly positive responses to food, are wanting to eat (or eating more) in response to the sight, smell or taste of palatable food, and a higher level of emotional overeating. In combination, these eating behaviours can lead to overeating and subsequent weight gain.
Dr Pickard and the team have also shown that there are significant differences in children’s temperament and caregivers’ feeding practices between each of the four eating behaviour patterns. Children with avid eating are more likely to be active and impulsive, and their caregivers are more likely to give them food to regulate their emotions or to restrict food for health reasons. Children with avid eating were also less food secure than children who showed happy or typical eating behaviours.
Principal investigator of the project, Professor Jackie Blissett, said: “Whilst feeding practices are key intervention targets to change children’s eating behaviour and child weight outcomes, there has been little evaluation of how feeding practices interact with children’s food approach behaviours to predict eating behaviour.”
She explained that despite the knowledge of the influence of feeding practices on children’s weight, current public health advice is generic and does not reflect variability in children’s appetites. Parents and caregivers can be left feeling frustrated when trying to manage their child’s food intake. By defining the four eating behaviour profiles, this research project, which is funded by the Economic and Social Research Council and co-developed by Professor Claire Farrow, Dr Clare Llewellyn, Dr Moritz Herle, Professor Emma Haycraft and Dr Helen Croker will make it easier to identify the best feeding practices for each eating pattern and provide tailored, effective advice for parents.
Dr Pickard said: “Parents can use this research to help them understand what type of eating pattern their child presents. Then based on the child’s eating profile the parent can adapt their feeding strategies to the child. For example, children in the avid eating profile may benefit more from covert restriction of food, i.e., not bringing snacks into the home or not having foods on display, to reduce the temptation to eat foods in the absence of hunger. Whereas, if a child shows fussy eating behaviour it would be more beneficial for the child to have a balanced and varied selection of foods on show to promote trying foods without pressure to eat.”
The team has planned further research investigating avid eating behaviour and will invite the caregivers and their children into the specialist eating behaviour lab at Aston University to get a better picture of what avid and typical eating behaviours look like in a real-life setting. All the findings will be integrated and the researchers will work with parents to develop feasible and helpful feeding guidelines to reduce children’s intake of palatable snack foods.
Dr Nicoline Potgieter at the Paediatric and Special Needs Dental Care Unit
The landscape of paediatric dental care in South Africa is poised for a significant transformation, marked by the launch of the nation’s first specialised Paediatric and Special Needs Dental Care Unit. This pioneering initiative, a result of the dedicated efforts of the Department of Paediatric Dentistry of the University of the Western Cape (UWC), The Provincial Government of the Western Cape (PGWC) and Rotary Club, is set to revolutionise Paediatric Dentistry in South Africa. It promises enhanced efficiency, a reduction in anxiety for young patients and a sharpened focus on providing dedicated oral health services to children and especially children with special health care needs.
Working towards the acknowledgment of Paediatric Dentistry as a specialty in South Africa, the need for a dedicated, specialised, child-friendly facility was identified – particularly in the Western Cape. This project stands as a steadfast response to establish such a paediatric dental unit, promising to positively impact service delivery to the children of the Western Cape.
Dalene Swart, President of the Rotary Club of Bellville, is passionate about this transformative initiative. She underscores the present scenario wherein young patients often undergo dental procedures under general anaesthesia.
“The establishment of a dedicated paediatric dentistry surgery unit, equipped with the latest materials and state-of-the-art equipment, not only enhances service quality but also serves as an invaluable training ground for postgraduate students,” she says.
However, the impact transcends mere smiles; it represents a pivotal advancement in South African healthcare, focused on the oral health of children. This project is expected to increase treatment capacity in the field of Paediatric Dentistry, thereby alleviating the workload of local healthcare professionals. It will also foster disease prevention and treatment programmes, bolster healthcare systems, and in time, significantly reduce the burden of disease and need for care under general anaesthesia.
Dr Nicoline Potgieter, president of the South African Association of Paediatric Dentistry and course coordinator for the Masters programme in Paediatric Dentistry at UWC, emphasises the enduring plight of the children in South Africa, who are in dire need of expert oral health care. “It is important to note, oral health directly impacts general health which directly impacts quality of life. It is our responsibility to provide the basic health care needs of our children. The technological advances incorporated into the unit, support minimally invasive techniques and preventative dentistry and the environment is focused on making the dental visit more pleasant for the child patient. Hopefully this is the first of many dedicated paediatric and special needs units across South Africa!”
This project, scheduled for full implementation by the end of October 2023, is the outcome of a collaboration between dedicated Rotary Club participants and the Tygerberg Oral Health Centre, which is a joint platform between UWC and PGWC. It seamlessly aligns with the UWC mission to train paediatric dentists as specialists in South Africa, reaffirming the institution’s commitment to community health and well-being. Similarly, it aligns with PGWC that is dedicated to high quality service rendering to all patients. Under this initiative, the first paediatric dentists will receive specialised training each year, while hundreds of children will benefit from disease prevention and interventions.
The project, funded with a capital expenditure of R1.2 million, draws support from various sources, including cash contributions from the Rotary Club of Bellville, Rotary Foundation and six other Rotary Clubs from the UK, USA and Canada. A significant portion of the funds raised was allocated to state-of-the-art essential dental equipment, consumables, and building materials.
Swart concludes by underlining that this project transcends immediate community needs for specialised paediatric dental care; it is about advancing medical care in South Africa and laying the groundwork for the long-term sustainability and transformation of dental care needs. This is why it enjoys unwavering support from local Rotarians.
A three-year clinical trial has shown that the sublingual immunotherapy (SLIT) is safe in peanut-allergic children ages one to four, with a greater likelihood of desensitisation and remission the earlier the treatment began. SLIT approach where the treatment is given as a small amount of liquid under the tongue, instead of peanut flour that is mixed with other food and then eaten like it is during oral immunotherapy, or OIT.
Published in the Journal of Allergy and Clinical Immunology, this is the first randomised, controlled trial to investigate – in this young age group – the efficacy and feasibility of SLIT.
The study included 50 peanut-allergic children between the ages of one and four, randomised to receive 4mg peanut SLIT versus placebo. Participants were randomised 1:1 to receive either peanut SLIT or placebo. Desensitization to peanut was assessed by double-blind, placebo-controlled food challenge (DBPCFC) after three years of treatment.
Findings showed that peanut SLIT can be highly effective in treating peanut-allergic toddlers with almost 80% tolerating 15 peanuts without allergic symptoms after completing the treatment. With most typical peanut-allergic reactions being caused by one peanut or less, these results would translate into strong protection against exposures to peanut. In addition, researchers showed that remission of the peanut allergy may be possible after peanut SLIT with 63% of the toddlers maintaining their protection three months after stopping the treatment. These new findings show that early intervention with peanut SLIT is promising and warrants further development.
Led by Edwin Kim, MD, associate professor of paediatrics at the UNC School of Medicine, said: “From our prior studies in older children, we were optimistic that peanut SLIT could have a similar treatment effect in toddlers.
“However, what we found was even better. The desensitisation levels we saw were higher than expected and on par with levels we normally would only expect with oral immunotherapy. Just as important, rather than wearing off quickly, we were excited to see that over 60% stayed protected three months after stopping the treatment.”
One of the presumed strengths of the SLIT approach when compared to OIT has been its overall safety and simple administration. While most treatment side effects with OIT are mild to moderate, severe reactions requiring emergency treatment do occur and there remains a critical need to develop treatments with more manageable side effects.
“Peanut OIT is currently available and being offered by increasing numbers of allergists, however we are quickly learning that in addition to its known risk of allergic reactions, the actual doing of OIT can be very difficult for many families,” said Kim. “Peanut SLIT could be a good option to consider as it may be able to provide comparable levels of protection while being safe and easier to administer.”
Compared to OIT, the SLIT approach is likely to be a safer option, Kim said, with the most common side effect consisting of oral itching. Treatments that can protect children from allergic reactions while still being safe and practical for busy families can be life-changing, and researchers are hopeful that peanut SLIT can be one of those options.
“Even with the push to introduce peanut in early childhood in order to prevent the allergy, peanut allergy remains one of the most common food allergies,” said Kim. “A result of early peanut introduction is that we are diagnosing peanut allergy at younger and younger ages making it vitally important to develop treatments that can be safe and effective at preventing allergic reactions in these young children.”
Figure I Neural measurement tools for studying the emergence of consciousness. Examples of techniques for recording brain activity and/or neuroimaging in infants and foetuses. (A) Infant electroencephalography (EEG) with a geodesic electrode net. (B) Foetal magnetoencephalography (MEG) recorded from a pregnant woman. (C) Infant functional near infrared spectroscopy (fNIRS) recording with multichannel optode cap. (D) An infant is prepared for functional magnetic resonance imaging (fMRI). Source: Bayne et al., 2023
There is evidence that some form of conscious experience is present by birth, and perhaps even in late pregnancy, an international team of researchers has found. The findings, published today in Trends in Cognitive Science, have important clinical, ethical and potentially legal implications, according to the authors.
Converging evidence from studies of functional network connectivity, attention, multimodal integration, and cortical responses to global oddballs suggests that consciousness is likely to be in place in early infancy and may even occur before birth. Over the decades, theorists have argued that consciousness emerges from anywhere from 30 to 35 weeks of pregnancy (based on EEG of the foetus’s brain) to 12 to 15 months of age (based on higher-order representational theory).
In the study, the researchers argue that by birth the infant’s developing brain is capable of conscious experiences that can leave a lasting imprint on their developing sense of self and understanding of their environment.
The team comprised neuroscientists and philosophers from Monash University, in Australia, University of Tübingen, in Germany, University of Minnesota, in the USA, and Trinity College Dublin.
Although each of us was once a baby, infant consciousness remains mysterious, because infants cannot tell us what they think or feel, explains one of the two lead authors of the paper Dr Tim Bayne, Professor of Philosophy at Monash University.
“Nearly everyone who has held a newborn infant has wondered what, if anything, it is like to be a baby. But of course we cannot remember our infancy, and consciousness researchers have disagreed on whether consciousness arises ‘early’ (at birth or shortly after) or ‘late’ – by one year of age, or even much later.”
To provide a new perspective on when consciousness first emerges, the team built upon recent advances in consciousness science. In adults, some markers from brain imaging have been found to reliably differentiate consciousness from its absence, and are increasingly applied in science and medicine. This is the first time that a review of these markers in infants has been used to assess their consciousness.
Co-author of the study, Lorina Naci, Associate Professor in the School of Psychology, who leads Trinity’s ‘Consciousness and Cognition Group, explained: “Our findings suggest that newborns can integrate sensory and developing cognitive responses into coherent conscious experiences to understand the actions of others and plan their own responses.”
The paper also sheds light into ‘what it is like’ to be a baby. We know that seeing is much more immature in babies than hearing, for example. Furthermore, this work suggests that, at any point in time, infants are aware of fewer items than adults, and can take longer to grasp what’s in front of them, but it is easier for them to process more diverse information, such as sounds from other languages.
For the management of children’s cancer symptoms, cannabis products have increased in popularity, but questions remain over their efficacy and safety. A recent review of published studies to date shows a lack of evidence to determine the dosing, safety, and efficacy of medical marijuana or cannabis-containing products for managing symptoms experienced by children with cancer. The analysis is published online in CANCER, a peer-reviewed journal of the American Cancer Society.
Although great strides have been made in treatments for childhood cancer, even leading to cures for many patients, many children still suffer from symptoms such as pain, anxiety, and weight loss related to cancer and its treatment. Over the last decade, cannabis products, both synthetic cannabinoids and natural phytocannabinoids, have gained popularity with patients and families for managing such symptoms, but paediatric oncologists are cautious to authorise cannabis for their patients given the limited data to inform dosing, product selection, and safety monitoring.
To provide insights for clinicians and parents, and to inform an upcoming clinical trial, a team led by Lauren E. Kelly, PhD, associate professor of pharmacology and therapeutics in the Rady Faculty of Health Sciences at the University of Manitoba, searched the medical literature to summarise existing knowledge about the potential benefits and harms of cannabis products in children with cancer.
The investigators identified 19 unique studies with a total of 1927 participants with cancer: eight retrospective chart reviews, seven randomised controlled trials, two open‐label studies, and two case reports. The products studied included medical-grade cannabinoids (such as the prescription drug nabilone), synthetic cannabinoids, and unspecified cannabis herbal extracts. Products were most commonly used to manage chemotherapy‐induced nausea and vomiting.
In the randomised controlled trials, patients who used cannabinoids were more likely to experience drowsiness, feeling high, dizziness, and dry mouth. Also, trial participants who received cannabinoids were almost four times more likely to drop from the study due to adverse events, compared with the control group who received placebo. Across all included studies, no serious cannabis‐related adverse events were reported.
Dr Kelly and her colleagues noted that most studies did not adequately describe the types, dosing, frequencies, and routes of administration of cannabis products, and outcomes were mixed and were reported in different ways. Therefore, researchers should develop standards for reporting cannabis exposures, cannabis‐related effects, and patient outcomes.
“It was difficult to measure benefit across studies, given a range of different outcomes and study designs; however, in interventional studies with active control groups, cannabinoids performed better in managing nausea and vomiting. Data are lacking on cannabinoids’ effects on pain, mood, sleep, and health-related quality of life,” said Dr Kelly. “Given that some children report benefits and some children experience adverse events, it is critical that more rigorous studies evaluating the effects of cannabinoids on children with cancer are conducted and shared with parents, patients, and the health care community.”
This literature review informed the design of a three-arm tolerability trial later this year.
