A study using Swedish health registers had found that inflammatory bowel disease (IBD) is an independent risk factor for serious infection, even at very low levels of gastrointestinal inflammation.
IBD is an umbrella term for chronic inflammatory bowel diseases, with a population prevalence of around 0.5%. The main types of IBD are ulcerative colitis and Crohn’s disease. Unlike irritable bowel syndrome (IBS), IBD results in visible damage to the intestinal mucous membrane.
In IBD, periods of high disease activity are sometimes followed by longer periods of low or no activity. However, the extent to which IBD patients with low disease activity are also at increased risk of serious infections, including sepsis, has been unclear.
The current study, published in the journal Clinical Gastroenterology and Hepatology, included data on more than 55 000 people diagnosed with IBD. ‘Serious infections’ was defined as infections requiring hospitalisation.
The difference between healed and unhealed
The results show that during periods of low disease activity but active gastrointestinal inflammation, known as microscopic inflammation, there was an increased risk of being affected by serious infections compared to periods of microscopically healed intestinal mucosa.
In the case of microscopic inflammation, the number of serious infections was 4.62 per 100 people per year. The corresponding figure for microscopically healed mucosa was 2.53. This corresponded to a 59% relative risk increase for residual microscopic gastrointestinal inflammation, on adjusting the results for various confounders.
Interestingly, the results held true even after adjusting for the prescribed IBD medications, and were otherwise similar regardless of age group, sex, and level of education.
Healing provides important protection
First and corresponding author Karl Mårild, an associate professor in paediatrics at the University of Gothenburg’s Sahlgrenska Academy, explained: “We have shown that even during periods of microscopic intestinal inflammation, IBD patients have an increased risk of serious infections, including sepsis, compared to periods when they have a microscopically healed mucosa. This is also true for patients who appear to have low-active disease in clinical terms, but who have microscopic intestinal inflammation beneath the surface.
“The results indicate that achieving a fully healed intestinal mucosa in IBD may reduce the risk of serious infections. This is important, as serious infections currently contribute toward increased morbidity and mortality in both children and adults with IBD.”
The results from the study are based on data from a national cohort (ESPRESSO) with information from Swedish health registers, and from the quality register for IBD (SWIBREG) on people in Sweden diagnosed with IBD between 1990 and 2016. This information was linked to data from microscopic intestinal examinations of patients with IBD.
Photo by Towfiqu barbhuiya: https://www.pexels.com/photo/person-feeling-pain-in-the-knee-11349880/
In a study published in Nature Medicine, investigators explored the mesenchymal stem cells’ potential as a game-changing treatment option for knee osteoarthritis. This type of treatment seeks to regenerate damaged tissue, treating the problem directly instead of seeking only to relieve symptoms. However, the availability of robust data from well-designed randomised controlled trials has been limited, particularly in comparison to the gold-standard of treatment for knee osteoarthritis (OA), corticosteroid injections (CSI).
Characterised by extensive damage to joints and debilitating pain, knee OA affects millions of people worldwide is the most common cause of chronic knee pain and has long posed a substantial clinical and economic burden.
In spite of advances in diagnosis, medications, and short-term pain management solutions, the elusive goal of a disease-modifying OA drug has remained out of reach. In recent years though, the use of stem cell therapy has gained traction as a promising alternative to surgery and for improving patients’ quality of life.
The initial findings of this study describe a first-of-its-kind randomized clinical trial to identify the most effective source of cellular injections for knee OA. The research team compared three types of cellular preparations, including autologous bone marrow aspirate concentrate (BMAC), autologous stromal vascular fraction (SVF), and allogenic human umbilical cord tissue MSCs (UCT) against CSI. The primary outcome measures were the visual analogue scale (VAS) and the Knee Injury and Osteoarthritis Outcome Score (KOOS) for pain from baseline to one year. The question driving the research was whether cell therapies could outperform corticosteroids in the treatment of knee osteoarthritis at the one-year mark.
While the findings showed each group had a measurable improvement in pain and function, there was no significant advantage to using any of the tested cell products compared to the gold standard anti-inflammatory corticosteroid treatment at the 12-month follow-up regarding the change in VAS pain score from baseline. Similarly, the analysis of the KOOS pain score produced consistent results, with no significant differences between groups at the 12-month mark in the change in score from baseline.
“The study demonstrated no superiority of any cell therapy over corticosteroids in reducing pain intensity over the course of a year,” says Scott D. Boden, MD, director of the Emory Orthopaedics and Spine Center, and a senior author on the study. “While there is much enthusiasm about the regenerative capacity of stem cells, the findings call into question the comparative effectiveness of various injections for knee osteoarthritis and underscores the importance of a personalised approach in selecting the right treatment for each patient’s unique needs.”
The study’s extensive reach also extended to evaluating the safety of these procedures measuring every adverse reaction, ranging from mild joint discomfort and swelling to unrelated hospitalisations. Importantly, the study found no study-related serious adverse events or symptomatic knee infections across any of the treatment groups at any point during the follow-up.
According to Dr Boden, future papers from the ongoing analysis of our data will determine if certain subgroups of patients might preferentially benefit from one of these treatments more than another. The findings offer an important step forward in answering key questions about the comparative effectiveness of certain OA treatment options, but more in-depth analysis using MRIs and cellular analysis of each injectate will continue to help inform standards of care.
A trial of a hormone replacement therapy that more closely replicates the natural circadian and ultradian rhythms of hormones has shown to improve symptoms in patients with adrenal conditions. Results from the University of Bristol-led clinical trial are published in the Journal of Internal Medicine.
Low cortisol levels typically result from conditions such as Addison’s and Congenital Adrenal Hyperplasia. The hormone regulates a range of vital processes, from cognitive processes such as memory formation, metabolism and immune responses, through to blood pressure and blood sugar levels. When low, it can trigger symptoms of debilitating fatigue, nausea, muscle weakness, dangerously low blood pressure and depression. Although rare, these adrenal conditions require lifelong daily hydrocortisone replacement therapy.
Although existing oral hormone replacement treatment can restore cortisol levels, it is still associated with an impaired quality of life for patients. Scientists believe this is because the current treatment does not mimic the body’s normal physiological timing, missing cortisol’s anticipatory rise and lacking its underlying ultradian and circadian rhythms.
The new ‘Pulsatility’ therapy, the culmination of ten years research by the Bristol team, is designed to deliver standard hydrocortisone replacement to patients via a pump which replicates more closely cortisol’s natural rhythmic secretion pattern. The pulsatile subcutaneous pump has now revealed promising results in its first clinical trial.
The double-blinded PULSES six-week trial recruited 20 participants aged 18 to 64 years with adrenal insufficiency conditions. They treated with usual dose hydrocortisone replacement therapy administered either via the pump or the standard three times daily oral treatment.
While only psychological and metabolic symptoms were assessed during the trial, results revealed the pump therapy decreased patient fatigue by approximately 10%, improved mood and increased energy levels by 30% first thing in the morning – when many patients struggle the most. MRI scans also revealed alteration in the way that the brain processes emotional information.
Dr Georgina Russell, Honorary Lecturer at the University’s Bristol Medical School, and the lead author, explained: “Patients on cortisol replacement therapy often have side effects which makes it difficult for them to lead normal lives. We hope this new therapy will offer greater hope for the thousands of people living with hormone insufficiency conditions.”
Stafford Lightman, a neuroendocrinology expert and Professor of Medicine at Bristol Medical School: Translational Health Sciences (THS), and the study’s joint lead author, added: “Besides reduction in dosage, cortisol replacement has remained unchanged for many decades. It is widely recognised that current replacement therapy is unphysiological due to its lack of pre-awakening surge, ultradian rhythmicity, and post dose supraphysiological peaks. The new therapy clearly shows that the timing of cortisol delivery, in line with the body’s own rhythmic pattern of cortisol secretion, is important for normal cognition and behaviour.
Relief could be on the way for people with painful hand osteoarthritis after a new study found an affordable existing drug can help. Until now there has been no effective treatment.
Published in The Lancet, the paper investigated methotrexate, a low-cost, effective treatment for inflammatory joint conditions such as rheumatoid arthritis and psoriatic arthritis. It has been widely used in Australia and globally since the early 1980s.
Researchers led by Monash University and Alfred Health found that methotrexate reduced symptoms in those with hand osteoarthritis (OA). A 20mg weekly oral dose over six months had a moderate effect in reducing pain and stiffness in patients with symptomatic hand OA.
Hand OA is a disabling condition that causes pain and affects function, impeding daily activities such as dressing and eating. It can significantly reduce quality of life. About one in two women and one in four men will experience symptoms from hand OA by the time they turn 85.
About half will have inflamed joints, which cause pain and are associated with significant joint damage. Despite the high prevalence and disease burden, there are no effective medications.
Senior author Professor Flavia Cicuttini said that the study identified the role of inflammation in hand OA and the potential benefit of targeting patients who experience painful hand OA.
“In our study, as with most studies of osteoarthritis, both the placebo group and methotrexate groups’ pain improved in the first month or so,” Professor Cicuttini said.
“However, pain levels stayed the same in the placebo group but continued to decrease in the methotrexate group at three and six months, when they were still decreasing. The pain improvement in the methotrexate group was twice as much as in the placebo group.
“Based on these results, use of methotrexate can be considered in the management of hand osteoarthritis with an inflammatory pattern. This provides clinicians with a treatment option for this group, which tends to get more joint damage.”
Professor Cicuttini said in patients with hand OA and inflammation, the effects of methotrexate were present at about three months and by six months it was very clear if it worked.
“At that time patients and their doctors can decide whether to continue or stop it,” she said. “This is very similar to what we currently do with other forms of inflammatory arthritis.”
The randomised, double-blind, placebo-controlled trial of 97 people with hand OA and MRI-detected inflammation assessed whether 20mg of methotrexate weekly reduced pain and improved function compared to placebo in patients with symptomatic hand OA and synovitis (inflammation) over six months.
Professor Cicuttini said the results could provide relief for people with hand OA inflammation, which was particularly common in women as they experienced menopause.
“Further trials are needed to establish whether the effect of methotrexate extends beyond six months, for how long we need to treat patients, and whether methotrexate reduces joint damage in patients with hand osteoarthritis and associated inflammation,” she said.
Professor Cicuttini now plans to conduct an extension trial to address these questions, in particular whether women who develop hand OA around menopause and often have severe pain and joint damage may benefit.
A new study from Queen Mary University of London, published in The Lancet’s EClinicalMedicine, has found that people may experience long-term symptoms, termed ‘long colds’, after non-COVID acute respiratory infections.
The ‘long cold’s’ most common symptoms included coughing, stomach pain, and diarrhoea more than four weeks after the initial infection. While the severity of an illness appears to be a key driver of risk of long-term symptoms, just why some people suffer extended symptoms while others do not is a focus of further research.
The findings suggest that there may be long-lasting health impacts following non-COVID acute respiratory infections such as colds, influenza, or pneumonia, that are currently going unrecognised. However, the researchers do not yet have evidence suggesting that the symptoms have the same severity or duration as long COVID.
The research compared the prevalence and severity of long-term symptoms after an episode of COVID versus an episode of another acute respiratory infection that tested negative for COVID. Those recovering from COVID were more likely to experience light-headedness or dizziness and problems with taste and smell compared to those who had a non-COVID respiratory infection.
While long COVID is now a recognised condition, there have been few studies comparing long-term symptoms following SARS-CoV-2 coronavirus infection versus other respiratory infections.
The study is the latest output from COVIDENCE UK, Queen Mary University of London’s national study of COVID, launched back in 2020 and still in follow-up, with over 19 000 participants enrolled. This study analysed data from 10 171 UK adults, with responses collected via questionnaires and statistical analysis carried out to identify symptom clusters.
Giulia Vivaldi, researcher on COVIDENCE UK from Queen Mary University of London and the lead author of the study, said: “Our findings shine a light not only on the impact of long COVID on people’s lives, but also other respiratory infections. A lack of awareness – or even the lack of a common term – prevents both reporting and diagnosis of these conditions.
“As research into long COVID continues, we need to take the opportunity to investigate and consider the lasting effects of other acute respiratory infections.
“These ‘long’ infections are so difficult to diagnose and treat primarily because of a lack of diagnostic tests and there being so many possible symptoms. There have been more than 200 investigated for long COVID alone.”
Professor Valerie Mizrahi, a world-leading tuberculosis researcher and director of the Institute of Infectious Disease and Molecular Medicine at the University of Cape Town, is retiring at the end of the year. PHOTO: Nasief Manie/Spotlight
World-leading tuberculosis researcher Professor Valerie Mizrahi was 35 when her mother Etty started losing weight and coughing furiously. After healthcare professionals in Johannesburg failed to accurately diagnose her, it was a doctor in Plettenberg Bay who told Etty: “The good news is you don’t have lung cancer, the bad news is that you have tuberculosis (TB).”
At the time, Mizrahi’s two infant daughters – aged one and three years old – had been spending much time with their granny. And so Mizrahi found herself crushing TB prevention tablets into her children’s porridge with honey.
Etty was treated at the then-Rietfontein Hospital, the precursor to Sizwe Tropical Diseases Hospital in Johannesburg. “My mom got very ill,” recalls Mizrahi. “She almost died of TB. And then 10 years later, she had to have a lobe from one of her lungs removed because she was one of those unfortunate people who got post-TB fibrosis.”
This was the early 1990s. Mizrahi was then with the South African Institute for Medical Research (SAIMR) linked to the University of the Witwatersrand, where she established the Molecular Biology Unit. She had identified TB as a lurking problem in South Africa, particularly in mines and in hospitals, calling it “a worthy foe ripe with opportunity for scientific investigation” – a problem she felt not enough people were talking about. It had been a pivotal moment when TB entered her own home, one that she says galvanised her thinking.
“It was a dramatic eye-opener for me as a basic scientist,” she says. “It was traumatic because of the time it happened in my career. Our family suddenly being thrust into the world of TB control. We had all these questions like we didn’t know where my mum got it, was her TB drug-susceptible, and why it would take so long to find this out. I got to see first-hand how difficult it was to get answers…”
Born in 1958 to Etty and Morris in Harare, Zimbabwe, Mizrahi studied at the University of Cape Town (UCT), forging an unusual career path, veering from mathematics and chemistry to biochemistry, genetics, and microbiology. In a male-dominated field, she became one of the first in South Africa to interrogate TB at a basic science level – that is to say, research aimed at advancing our understanding of the basic science of how TB bacteria survive, replicate, and resist attempts to kill it.
‘the only good TB bacillus is a dead one’
Discussing TB, Mizrahi’s passion is effervescent, her every second sentence punctuated with “okay”. These underscore her statements – subtle pauses allowing for her preceding words to sink in.
Source: CC0
…there’s a reason why TB has persisted for so long. The bacillus is pretty hard to kill. It’s built like Fort Knox.
Prof Valerie Mizrahi
A particular interest for Mizrahi is developing antibiotics “that can kill this bacterium stone cold dead”.
“To me, the only good TB bacillus is a dead one,” she says. “But there’s a reason why TB has persisted for so long. The bacillus is pretty hard to kill. It’s built like Fort Knox. So it’s a monumental challenge. We don’t know where all the bacteria are residing. We know that TB in an infected lung is sitting in really difficult places, hard places for drugs to get to. This notion of going after the bacillus with drugs and just slamming it is a tough problem. Not insurmountable, but there’s a lot of research that needs to be done.”
TB can be cured, but treatment typically takes at least six months and involves taking at least four different antibiotics, with side effects ranging from minor to serious. In addition to research on new antibiotics, there are also several experimental TB vaccines currently in late-phase studies. The only TB vaccine we have was developed more than a century ago and only has some moderate efficacy in kids.
The IDM
Since 2011 Mizrahi has served as director of the Institute of Infectious Disease and Molecular Medicine (IDM) – the University of Cape Town’s (UCT) largest cross-faculty research unit with over 800 affiliated staff and grants running into hundreds of millions of rands.
Mizrahi’s glass-encased office looks directly onto Table Mountain and hospital bend – where, at the time of our interview, N2 traffic out of Cape Town is already at a standstill. Behind her desk, Mizrahi quips. “Yes, this is the most beautiful office at UCT, everyone agrees…” Below, students can be seen milling about on the health sciences campus.
Last year in its Best Global Universities 2022-2023 survey, online portal US News ranked UCT as 24th best university in the world for studying infectious diseases. Mizrahi is ambivalent about the IDM taking credit for this accolade. She notes that this success is founded on problems of a “confounding and overwhelming” scope, with many diseases being proxies for poverty and inequality in South Africa.
The IDM’s focus includes TB, HIV/AIDS, COVID-19, other infectious diseases like sexually transmitted infections, and non-communicable diseases such as preventable cancers, cardiovascular, and psychiatric disorders.
Reflecting on the IDM, she says they have accrued a “research ecosystem – a concentration of expertise, something resembling critical mass” – bringing together specialists across the basic, clinical, and public health sciences, in one place.
“We’ve got Groote Schuur Hospital across the road,” she says. “We have geneticists and biochemists, virologists, and immunologists. There’s a clinician across the corridor from me, bioinformaticians, and microscopists downstairs. If you are the kind of researcher who revels in asking questions and finding people who can answer them, then this is the place for you.”
Going forward, multi-disciplinary research is what excites her. “HIV and TB have been so dominant in the narrative of this country. But now when you look at the figures and the data, we are dealing with a huge burden of non-communicable disease on top of infectious diseases,” she says. “The key question moving forward is how not to think in silos.”
Polymaths and dilettantes
This, she says, takes humility.
“To do this, one has to be very humble. You need to know what you don’t know. People who work really well in interdisciplinary spaces are those who understand the limits of their own specialist knowledge, and the need to listen to where another person is coming from.”
She distinguishes between polymaths and dilettantes. “You have to be careful not to be a dilettante, who knows a little about a lot. Research can be very superficial in that way. So I have my antenna out all the time to distinguish between polymaths, who really are people who know a lot about a lot, and dilettantes who know a little about a lot. And well, in this institute we have a lot of polymaths, brilliant researchers who move across disciplines, very interesting people to work with.”
With a string of awards and an A1-rating from South Africa’s National Research Foundation, earlier this year, Mizrahi was elected a fellow of the Royal Society, the United Kingdom’s National Academy of Sciences. However, she recalls humbling moments along the way – like the time she flew to London seven months pregnant with her second child, for her first-ever interview with the Wellcome Trust committee to secure funding. “I was so confident, but I was ill-prepared,” she says. “They savaged me! I tried to frame it not as a failure but as a learning experience.”
Passing the baton
At the end of this year, Mizrahi will pass on the baton when she retires. Of her achievements, she is proudest of young scholars she has helped to shape. “Their legacies will last much longer than a few more citations of a publication,” she says.
Mizrahi notes more and more women leaders in her field. For example, recently, while delivering a talk at the Weizmann Institute in Israel, she noticed chemist and Nobel laureate Ada Yonath in the room. “Talk about a role model; I was almost in tears.”
Studying at UCT, Mizrahi’s own mentors had mostly been men – something she didn’t even notice, she says, as male professors treated her no different. What did cut her was racial segregation at the time, prompting a political awakening and stints leaving South Africa to work in the United States. First as a postdoctoral fellow at Pennsylvania State University and then at drug company, SmithKline & French in Philadelphia.
Her own background makes her sensitive to marginalised groups, she says. Her grandparents were Sephardi Jews who fled Rhodes Island, today part of Greece, ten years before World War II, to find refuge in Zimbabwe.
Having just read former UCT vice-chancellor Max Price’s book Statues and Storms: Leading a University Through Change, she says, “It took me back to some very difficult times. It’s harrowing and brave and made me realise that even though I was here in the midst of it [#feesmustfall and #rhodesmustfall protests], a senior person of the university, how little I really knew of what was going on. It really is a lesson in crisis leadership.”
There’s no control experiment to life, you can’t go back and redo it.
Mizrahi lives in Sea Point with her one daughter. Her other daughter is based in Vancouver. Here, she likes to park her car at the end of the week, walking around – “either listening to a New York Times podcast or a beautiful piece of music and that’s when I think.”
She describes herself as an introvert who needs personal time to stay sane. She is deeply thoughtful about her roots, wondering about a sense of belonging. “As white people in Africa, I think this is part of the reckoning we go through. I truly identify as being African. Arriving at Johannesburg, just breathing in the air, it feels like home.”
Looking back, Mizrahi notes her mother as a major influence in her life. “Not a highly educated woman. But the wisest, smartest person I know.” Etty still lives in Johannesburg while Morris has passed away. To this day, Etty thinks of herself as a proud TB survivor, says Mizrahi.
On her retirement, the scholar says, “Now it’s about opening up opportunities for others, writing a few papers, and contributing to the TB drug discovery space.”
“I’ve done the best I can,” she says, “I don’t believe in having regrets… There’s no control experiment to life, you can’t go back and redo it. But I don’t know that I could have done it any differently.”
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.”
New research from Queen Mary University of London, published in iScience, shows an increased risk of blood clots in women who have any combination of Factor V Leiden gene mutation, oestrogen use, or common medical conditions – specifically: obesity, high blood pressure, high cholesterol, and kidney disease.
Women with the Factor V Leiden (FVL) gene mutation who had been prescribed oestrogen had more than double the risk of blood clotting compared to women who did not have this mutation. And almost 20% of the women who carry FVL, were prescribed oestrogen and had two medical conditions suffered a blood clot. The presence of the FVL gene made a substantial difference to risk, with only around 5% of women taking oestrogen and having two conditions suffering a clotting event.
The study also found that a woman with obesity, hypertension, high cholesterol, and kidney disease (not uncommon in a clinical setting) had an 8 times greater chance of blood clotting compared to a woman with none of these conditions. This amounted to roughly one in every six women with the four conditions in the study suffering a blood clot. Three medical conditions meant a five times greater chance of blood clotting, and two medical conditions meant a two times greater chance.
One in three women who had the FVL gene mutation and three of the medical conditions examined also suffered a blood clotting event.
The researchers examined the health data of 20 048 British-Bangladeshi and British-Pakistani women from the Genes & Health project, a large community-based genetics study. While oestrogen use, FVL, and common medical conditions are all known risk factors of blood clots, studies have not looked at the combined risk of these factors together on blood clot prevalence.
Women are commonly prescribed oestrogen, both through oral contraception containing the hormone and as part of post-menopausal hormone replacement therapy.
Professor Sir Mark Caulfield, from Queen Mary University of London, said: “Our study gives a more complete picture of blood clotting in Bangladeshi and Pakistani communities who have previously been underrepresented in research.
“Genetic testing of the FVL gene mutation could give a clearer sense of someone’s personalised risk of this potentially fatal complication if they were prescribed oestrogen.”
Despite strenuous control efforts, hospital-acquired infections still occur – the most common of which is caused by the bacterium Clostridioides difficile, which creates lingering spores and resists alcohol-based hand sanitisers. Surprising findings from a new study in Nature Medicine suggest that the burden of C. diff infection may be less a matter of hospital transmission and more a result of characteristics associated with the patients themselves.
The study team, led by Evan Snitkin, PhD; Vincent Young, MD, PhD; and Mary Hayden, MD, leveraged ongoing epidemiological studies focused on hospital-acquired infections that enabled them to analyse daily faecal samples from every patient within the intensive care unit at Rush University Medical Center over a nine-month period.
Arianna Miles-Jay, a postdoctoral fellow in Dr Snitkin’s lab, analysed 1141 eligible patients, and found that a little over 9% were colonised with C. diff. Using whole genome sequencing at U-M of 425 C. difficile strains isolated from nearly 4000 faecal specimens, she compared the strains to each other to analyse spread. But she found that, based on the genomics, there was very little transmission.
Essentially, there was very little evidence that the strains of C. diff from one patient to the next were the same, which would imply in-hospital acquisition. In fact, there were only six genomically supported transmissions over the study period. Instead, people who were already colonised were at greater risk of transitioning to infection.
“Something happened to these patients that we still don’t understand to trigger the transition from C. diff hanging out in the gut to the organism causing diarrhoea and the other complications resulting from infection,” said Snitkin.
Hayden notes this doesn’t mean hospital infection prevention measures are not needed. In fact, the measures in place in the Rush ICU at the time of the study – high rates of compliance with hand hygiene among healthcare personnel, routine environmental disinfection with an agent active against C. diff, and single patient rooms were likely responsible for the low transmission rate. The current study highlights, though that more steps are needed to identify patients who are colonised and try to prevent infection in them.
Where did the C. diff come from? “They are sort of all around us,” said Young. “C. diff creates spores, which are quite resistant to environmental stresses including exposure to oxygen and dehydration…for example, they are impervious to alcohol-based hand sanitiser.”
However, only about 5% of the population outside of a healthcare setting has C. diff in their gut – where it typically causes no issues.
“We need to figure out ways to prevent patients from developing an infection when we give them tube feedings, antibiotics, proton pump inhibitors – all things which predispose people to getting an actual infection with C. diff that causes damage to the intestines or worse,” said Young.
The team next hopes to build on work on AI prediction for patients at risk of C. diff infection to identify patients more likely to be colonised and who could benefit from more focused intervention.
Said Snitkin, “A lot of resources are put into gaining further improvements in preventing the spread of infections, when there is increasing support to redirect some of these resources to optimise the use of antibiotics and identify other triggers that lead patients harbouring C. diff and other healthcare pathogens to develop serious infections.”
In a study published in the journal Nanoscale, researchers encased Narasin, a new antibacterial compound, in tiny, soft nanoparticles 1000 times smaller than a single strand of human hair and applied in a gel form to targeted acne sites. The University of South Australia (UniSA)-led research team found that the drug proved successful against drug-resistant acne bacteria and delivered via nanocarriers achieved a 100-fold increase in absorption than simply taken with water.
Lead author UniSA PhD student Fatima Abid says this is the first time that nano-micelle formulations of Narasin have been developed and trialled.
“Acne severely impacts approximately 9.4% of the world’s population, mainly adolescents, and causes distress, embarrassment, anxiety, low self-confidence and social isolation among sufferers,” Abid says.
“Although there are many oral medications prescribed for acne, they have a range of detrimental side effects, and many are poorly water soluble, which is why most patients and clinicians prefer topical treatments.”
Abid’s supervisor, pharmaceutical scientist Professor Sanjay Garg, says a combination of increasing antibiotic resistance and the ineffectiveness of many topical drugs to penetrate hair follicles in acne sites means there is a pressing need to develop new antibacterial therapies that are effective and safe.
Narasin is commonly used for bacterial infections in livestock but has never been previously investigated as a viable treatment for acne.
Abid, Prof Garg and researchers from UniSA, the University of Adelaide, and Aix-Marseille Université in France also investigated how well Narasin encased in nanoparticles penetrated various layers of skin, using pig’s ear skin as a model.
“The micelle formulation was effective in delivering Narasin to acne targets sites, as opposed to the compound solution which failed to permeate through skin layers,” Prof Garg says.
