Category: Diseases, Syndromes and Conditions

Categories : Diseases, Syndromes and Conditions VaccinesTags :

TB Vaccine Shown to Protect Against Common Infections

On By ModernMedia

The tuberculosis (TB) vaccine Bacillus Calmette-Guerin (BCG) could protect newborns against a variety of common infections, such as upper respiratory tract infections, chest infections, and diarrhoea, according to a new study from the London School of Hygiene and Tropical Medicine (LSHTM).

It has been known that BCG protects against diseases other than TB, offering protection against non-tuberculous mycobacteria infection like leprosy and Buruli ulcer. It is also used in the treatment of superficial carcinoma of the bladder.

However, this is the first research to rigorously investigate the full range. The results suggest that vaccinating all babies with BCG on their day of birth could save lives by reducing neonatal infections in areas with high rates of infectious disease.

The study involved a randomised control trial of 560 newborns in Uganda, who were monitored for a range of illnesses. After six weeks, infection rates from any disease were 25% lower in the group that received the vaccine at birth, compared to the group that had not yet received the vaccination. The most protected appeared to be vulnerable groups such as low birth weight babies, and boys. Importantly, BCG appeared to protect against even severe infections.

Sarah Prentice, the lead author from LSHTM, said: “Nearly a million babies die every year of common infections so we urgently need better ways to protect them. Our research suggests that ensuring that BCG is given at birth could make a big difference in low-income countries, potentially saving many lives.”

The newborns were randomly assigned to receive BCG either at birth or at six weeks of age. They were followed-up by doctors, blinded to the intervention, for 10 weeks, who looked for any type of illness or infection.

The research team then compared how often infants in the two groups presented to doctors with infections of any kind, except TB, to see whether having BCG made a difference. They also took blood samples from both groups, to look at differences in their innate immune system, the body’s first line of defense against infections.

Infants vaccinated with BCG at birth presented to doctors with any kind of infection 25% less often than infants who had not. BCG seemed to protect against all kinds of infections, such as common colds, chest infections, and skin infections.

After the delayed group had been vaccinated, the rates of infection were identical between the two groups: the delayed group’s immunity ‘brought up to speed’ when they received BCG.

Study co-author Prof Hazel Dockrell, LSHTM, said: “It’s very exciting to think that BCG vaccination might help keep newborns safe against other dangerous infections, in addition to providing protection against TB. Although BCG is recommended at birth in many countries, it is often delayed due to logistical difficulties. Ensuring that the vaccine is given on day one, in areas with high rates of infectious disease, could have a major impact on infections and deaths in the newborn period.”

Though the study could not definitely determine whether the BCG vaccine was responsible for the lowered rate of infections, there is nonetheless great interest in applying the vaccine as a protection for novel disease outbreaks, such as COVID or Ebola, before a specific vaccine can be developed.

Dr Prentice said, “Since the findings show that BCG seems to offer wider protection against a range of infections, our study also raises hopes it might be useful in protecting the general population against COVID-19 and future pandemics – though we will need to see the results of other, more specific studies to know for sure.”

Source: News-Medical.Net

Journal information: Prentice, S., et al. (2021) BCG-induced non-specific effects on heterologous infectious disease in Ugandan neonates: an investigator-blind randomised controlled trial. The Lancet Infectious Diseases. doi.org/10.1016/S1473-3099(20)30653-8.

Categories : Diseases, Syndromes and Conditions GeneticsTags :

Excessive False Positives from SNP Testing in Very Rare Diseases

On By ModernMedia

A widely-used genetic testing technology has a very high rate of false positives for extremely rare genetic diseases, a study has found.

Single nucleotide polymorphism (SNP) chips are DNA microarrays which test genetic variation at hundreds of thousands of specific genome locations. They were initially developed to study common genetic variations, and are excellent tools for tracing ancestry and aso detecting predisposition to common multifactorial diseases such as type 2 diabetes.

Prompted by accounts of women scheduling surgery because of wrongly being informed they had variations in the BRCA1 gene that could lead to very high risks of breast disease, a team from the University of Exeter set out to test the technology. Using data from 50 000 individuals, they found that the majority of rare disease detections were false.

“SNP chips are fantastic at detecting common genetic variants, yet we have to recognise that tests that perform well in one scenario are not necessarily applicable to others,” said senior author Caroline Wright, Professor in Genomic Medicine at the University of Exeter Medical School. “We’ve confirmed that SNP chips are extremely poor at detecting very rare disease-causing genetic variants, often giving false positive results that can have profound clinical impact. These false results had been used to schedule invasive medical procedures that were both unnecessary and unwarranted.”

The team compared data from the SNP chips to data from the UK Biobank which was sequenced with better technology, plus 21 volunteers sharing their consumer genetic data.

They found a false positive rate of 84% for variants that were 1 in 100 000. From the consumer data, 20 of the 21 had at least one false positive for a disease-causing variation.

Co-author Dr Leigh Jackson, Lecturer in Genomic Medicine at the University of Exeter, said the number of such false positives on SNP chips was “shockingly high.”

“To be clear: a very rare, disease-causing variant detected using a SNP chip is more likely to be wrong than right,” said Dr Jackson. “Although some consumer genomics companies perform sequencing to validate important results before releasing them to consumers, most consumers also download their ‘raw’ SNP chip data for secondary analysis, and this raw data still contain these incorrect results. The implications of our findings are very simple: SNP chips perform poorly for detecting very rare genetic variants and the results should never be used to guide a patient’s medical care, unless they have been validated.”

Source: Medical Xpress

Journal information: BMJ (2021). www.bmj.com/content/372/bmj.n214

Categories : Diseases, Syndromes and ConditionsTags :

Treating Periodontitis can Reduce Risks of Certain Other Diseases

On By ModernMedia

A steadily growing body of evidence points to a two-way connection between oral health and systemic disease.

Periodontitis, the inflammation and disease of tissues surrounding the teeth, is already known to be a result of type 2 diabetes, but there is research to suggest that it may also cause diabetes—as well as certain other diseases.

“What happens in your body impacts your mouth, and that in turn impacts your body. It’s truly a cycle of life,” said Professor Purnima Kumar of The Ohio State University. “What is more dynamic than the gateway to your body – the mouth?” she continued. “It’s so ignored when you think about it, and it’s the most forward-facing part of your body that interfaces with the environment, and it’s connected to this entire tubing system. And yet we study everything but the mouth.”

The link between oral health and type 2 diabetes was first established in the 1990s, and Prof Kumar has led many investigations into this area. She was lead author in a study published last year that investigated the oral microbiomes of people with and without type 2 diabetes, and the effects of nonsurgical periodontitis treatment.

“Our studies have led up to the conclusion that people with diabetes have a different microbiome from people who are not diabetic,” Prof Kumar said. “We know that changing the bacteria in your mouth and restoring them back to what your body knows as healthy and friendly bacteria actually improves your glycemic control.”

The rough picture that has emerged is that oral bacteria are aerobic, but even small changes such as a few days of not brushing teeth can trigger a cascade that results in the bacteria shifting to an anaerobic, fermentative state producing toxins and byproducts. It becomes, as Prof Kumar puts it, “a septic tank” that stimulates the immune system and causes an inflammatory state, producing signalling products that bacteria then feed on.

“Then this community – it’s an ecosystem – shifts. Organisms that can break down protein start growing more, and organisms that can breathe in an oxygen-starved environment grow. The bacterial profile and, more importantly, the function of the immune system changes,” she explained.

The inflammation causes pores to open in the lining of the mouth, allowing the bacteria entry to the body.

“The body is producing inflammation in response to these bacteria, and those inflammatory products are also moving to the bloodstream, so now you’re getting hammered twice. Your body is trying to protect you and turning against itself,” Prof Kumar said. “And these pathogens are having a field day, crossing boundaries they were never supposed to cross.”

Though the relationship between oral health and certain disease is a complex one, Prof Kumar said prevention was exceedingly simple. Daily brushing and flossing with twice-yearly dentist visits for cleaning were sufficient.

Source: News-Medical.Net

Journal information: Kumar, P. S., et al. (2020) Subgingival Host-Microbial Interactions in Hyperglycemic Individuals. Journal of Dental Research. doi.org/10.1177/0022034520906842. 

Categories : Diseases, Syndromes and Conditions Hospitals PaediatricsTags :

Children with Sepsis Respond Better to ‘Relaxed’ Care Bundle

On By ModernMedia

Following a ‘relaxed care bundle’ was linked to lower 30-day mortality and shorter hospital stays among children with sepsis, according to preliminary data from the Improving Pediatric Sepsis Outcomes (IPSO) FACTO trial.

The study findings were presented virtually at the Society of Critical Care Medicine’s Critical Care Congress.

Sepsis is the leading cause of death in children, with an estimated 7.5 million deaths a year. Childhood sepsis includes severe pneumonia, severe diarrhoea, severe malaria, and severe measles. Some 25-40% of children who recover from sepsis still have long-term consequences.

The ‘relaxed’ sepsis bundle is based on a group of best evidence-based interventions. It involves an initial fluid bolus delivery within 60 minutes, as opposed to 20 minutes; and antibiotic delivery within 180 instead of 60 minutes. Accepted sepsis recognition protocols (screen, huddle, or care order) were also involved with the bundle.

This trial data came from about 40 000 patients with sepsis or suspected sepsis at a range of children’s hospitals across the US, from 2017 to 2019. Raina M Paul, MD, of Advocate Children’s Hospital, Illinois, USA reported the data, saying that the relaxed bundle saw better outcomes than the more original bundle which was more time-restrictive. 
Sepsis-attributable mortality fell by 48.9% among the relaxed bolus-compliant versus non-compliant group (3.1% vs 3.5%), and by 13.7% in original bundle-compliant vs non-compliant cases. Following all aspects of the relaxed bundle was associated with a reduction in median days in hospital from 9 to 6 days.

In a separate presentation, Kayla Bronder Phelps, MD, of CS Mott Children’s Hospital in Michigan, USA, reported the results of a study that showed children hospitalised for severe sepsis were likely to have longer hospital stays if they were from lower-income neighbourhoods. Using a national database, she identified 10 130 cases of children with severe sepsis. Severe sepsis hospitalisations were also highest among the lowest-income quartile, reflecting the fact that there were more children living in low-income neighbourhoods.

Overall, 8.4% of children in the cohort died of sepsis during hospitalisation, with no association between mortality rates and income level. However, children in the lowest-income areas spent a median 9 days in the hospital, while children from the highest-income areas spent 8 days.

Bronder Phelps noted that the study is among the first to examine the impact of poverty on paediatric sepsis outcomes. Poverty is a known risk factor for a wide range of paediatric diseases, such as neonatal bacterial infection, asthma, and migraine, and in adults, poverty is associated with poorer outcomes including higher mortality rates.

Source: MedPage Today

Presentation information 1: Paul R, et al “Improving pediatric sepsis outcomes for all children together (IPSO FACTO): Interim results” SCCM 2021; Abstract 32.

Presentation information 2: Phelps K, et al “The association of socioeconomic status and pediatric sepsis outcomes” SCCM 2021; Abstract 37.

Categories : COVID Diseases, Syndromes and ConditionsTags :

Nearly a Third of COVID Patients Are Readmitted to Hospital

On By ModernMedia

According to a study reported by The Telegraph, almost a third of COVID patients are readmitted to hospital later. The new study, still on the MedRxiv preprint server and not yet peer reviewed, was conducted by Leicester University and the Office for National Statistics (ONS).

Approximately 1 in 10 people who are infected with COVID go on to develop long COVID symptoms, which include breathlessness, excessive fatigue and muscle aches. This appears to be causing hospital readmissions – and deaths.

The study looked at 47 780 individuals with a primary diagnosis of COVID who had a hospital visit between 1 January 2020 and 31 August 2020, and a COVID-negative control group admitted over the same period. The mean follow-up time was 140 days for those with a COVID diagnosis, and during this team 29.4% were readmitted and 12.3% died. The study also found a higher risk in those under 70 and of ethnic minority groups in the UK, most notably in respiratory diseases.

Study author Kamlesh Khunti, professor of primary care diabetes and vascular medicine at Leicester University, said: “This is the largest study of people discharged from hospital after being admitted with Covid.

“People seem to be going home, getting long-term effects, coming back in and dying. We see nearly 30 per cent have been readmitted, and that’s a lot of people. The numbers are so large.”The message here is we really need to prepare for long Covid. It’s a mammoth task to follow up with these patients and the NHS is really pushed at the moment, but some sort of monitoring needs to be arranged.”

One finding which surprised the team was that many patients went back in and had a new diagnosis, such as liver, heart or kidney conditions, as well as diabetes. This means, according to Prof Khunti, that it is important for patients to receive follow-up and protective therapies such as statins or aspirin, adding: “We don’t know if it’s because Covid destroyed the beta cells which make insulin and you get Type 1 diabetes, or whether it causes insulin resistance, and you develop Type 2, but we are seeing these surprising new diagnoses of diabetes.”

Source: Yahoo News

Categories : Diseases, Syndromes and Conditions Gastrointestinal Immune SystemTags :

Taurine Boosts Microbiotic Defences in the Gut

On By ModernMedia

A new study has discovered that taurine has a role in triggering the gut’s microbiota to identify and destroy invading bacteria, such as Klebsiella pneumoniae, a bacteria commonly found in the gut and responsible for a variety of infections.

It is already known that gut microbiota can protect against infection, but it is not well understood how they accomplish this. A better of understanding of how they confer protection will aid the development of replacements for current antibiotic drugs, which currently harm gut microbiota and whose effectiveness is waning.

Taurine is a complementary (non-essential amino acid, involved in helping break down fats and is present in bile acid. Most taurine is produced by the body but some is also required in the diet. Certain seafoods, seaweed, poultry and beef are good sources of taurine.

The scientists believed that the taurine helped prevent against bacterial colonisation by producing hydrogen sulphide, but during their research they also discovered that a single infection was sufficient to prepare the gut microbiota to resist a second infection. The liver and gallbladder which produce and store bile acids, can develop long-term protection against infection.

While investigating further, the researchers discovered a particular type of bacteria, Deltaproteobacteria, which protected the gut against colonisation by infectious bacteria and which was activated by taurine. Taurine fed to mice in drinking water helped to shield against infection by boosting the function of the protective bacteria, but those fed bismuth subsalicylate (a common over-the-counter diarrhoea treatment), the infection protection diminished, because bismuth suppresses hydrogen sulphide production in the gut.

Source: News-Medical.Net

Categories : Diseases, Syndromes and Conditions T-cellsTags :

New Study Reveals T-Cell Role in Periodontitis and Bone Loss

On By ModernMedia

There are mechanisms involved in diseases of bone loss, such as periodontitis that are still not well understood, but an unexpected behaviour of a type of T-cell may shed new light on the matter.

Looking at periodontal disease in mice, scientists found that regulatory T (Treg) cells start behaving unexpectedly. They lose their ability to regulate bone loss and begin to promote inflammation instead.

“That is important because, in many therapies analyzed in in-vivo models, researchers usually check if the number of regulatory T cells has increased. But they should check if these cells are indeed functioning,” said lead author Dr Carla Alvarez, a postdoctoral researcher at the Forsyth Institute.

In periodontal disease, bone loss occurs because the immune system responds disproportionately, destroying tissue through inflammation. The Treg cells normally suppress the immune system but lose the ability to do so during periodontal disease.

Understanding this falls into the field of osteoimmunology, which is about understanding the interaction of bone metabolism and the immune system. “This is an interesting mechanism highlighting how the bone loss is taking place in periodontal disease,” said Dr Alpdogan Kantarci, at Forsyth and co-author of the paper.

A potential treatment for periodontal disease would involve reactivating the Treg cell’s immunosuppression function, but this is a complex, nonlinear task complicated by the fact that periodontal disease is initiated by oral microbes.

“The relationship between immune response and bone is not so straightforward,” said Alvarez. “There are multiple components. You have to imagine a complex network of signaling and cells that participate.”
The researchers’ next step is to examine the process in humans.

Source:Medical Xpress

Journal information: Alvarez, C., Suliman, S., Almarhoumi, R. et al. Regulatory T cell phenotype and anti-osteoclastogenic function in experimental periodontitis. Sci Rep 10, 19018 (2020). doi.org/10.1038/s41598-020-76038-w

Categories : Diseases, Syndromes and ConditionsTags :

A Growing Need to Expand Aneurysm Warnings for Fluoroquinolones

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New research suggests that the fluoroquinolone class of antibiotics may increase the risk of aortic aneurysm (AA).

In 2018 the US Food and Drug Administration added warnings for people at risk of aortic disease, based on data from its reporting system plus four epidemiological studies in other countries. According to a study by a team led by Melina Kibbe, MD at the University of North Carolina at Chapel Hill, cases of AA formation or dissection were 7.5 per 10 000 prescription fills for fluoroquinolones at 90 days compared with 4.6 per 10 000 fills for comparison antibiotics.

Fluoroquinolones include ciprofloxacin, gemifloxacin, levofloxacin, moxifloxacin, norfloxacin, and ofloxacin. The FDA had already warned that fluoroquinolones could cause tendon damage and rupture, peripheral nerve damage, mental health disturbance, hypoglycaemic coma and that they are associated with Clostridium difficile infection.

Using a database of health insurance claims for almost 28 million individuals aged 18 to 64,  the researchers searched for associations between fluoroquinolone prescriptions and aneurysms, compared to other antibiotic types.

Fluoroquinolones were associated with excess abdominal AAs (HR 1.31, 95% CI 1.25-1.37) and iliac artery aneurysms (HR 1.60, 95% CI 1.33-1.91), though associations with aortic dissection  or thoracic aortic aneurysm did not reach significance.

“As such, regional differences in the etiology, incidence, and clinical management of aortic disease in the thoracic vs abdominal aorta should be carefully considered,” wrote the researchers.

Adults over 35 also had a greater risk of AA with fluoroquinolones compared to younger cohorts. Limitations of the study included not controlling for the possibility of pre-existing aneurysms, or for the presence of risk factors such as smoking.

However, the researchers believe the results are significant enough to warrant attention. “Almost regardless, this large cohort study of a U.S. population suggests it is time once again to rethink the use of this class of antibiotics for patients with or without aortic disease,” they wrote.

Source: MedPage Today

Journal information: Newton E, Akerman A, Strassle P, Kibbe M. Association of Fluoroquinolone Use With Short-term Risk of Development of Aortic Aneurysm. JAMA Surg. 2021. doi:10.1001/jamasurg.2020.6165

Categories : COVID Diseases, Syndromes and ConditionsTags :

A Four Century Old Manual for Social Distancing Rules

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A feature article from the BBC details how one doctor in the era of the Plague created an eerily familiar set of social distancing guidelines that matches a lot of our non-pharmaceutical COVID controls.

Staying at home and only sending out one person to do the shopping, keeping six feet apart and disinfecting goods – all of these feature in a manual created over four centuries ago to help protect Alghero, a small Italian town against the plague. The methods by a doctor named  Quinto Tiberio Angelerio, published in a 57-page booklet on his methods, titled Ectypa Pestilentis Status Algheriae Sardiniae.

Unlike most plague outbreaks, it failed to spread to neighbouring areas and died out within eight months – though not without claiming about 60% of the town’s initial population of 6000. Angelerio’s rules are thought to be at least partly responsible.

Ravaging Europe as well as Asia and North Africa, the plague left an unimaginable mark on Western society; tunnelling projects in London regularly run into mass graves of plague victims. Italian poet Francesco Petrarca wrote that future generations would likely not be able to grasp the scale of the calamity, and he is probably right in that regard. The plague continued to reappear, and devastated regions when it did – The Great Plague of London saw 24% of its populace dying over 1665 to 1666.

Although the germ theory of disease was then still centuries in the future, and bathing in urine was thought to be effective treatment, physicians in Europe believed in the contagion theory, thinking that diseases were spread through “miasmas” or “bad air”. This enabled them to come up with the idea of quarantines, from the Italian for “forty days” which was the standard isolation period.

Facing huge obstacles from a recalcitrant citizenry, Angelerio nevertheless persevered and soon a lockdown was enacted. This was not unique, as whole cities would be quarantined. Other rules that were enforced included a social distancing of six feet (as measured by a pole to be carried around by anyone outside), advising people to be careful shaking hands during mass, as well as railing preventing customers coming into contact with shopkeepers. He also used superstition to keep people in line, as European people of the time believed the plague to be divine punishment – although rule breakers were common, as they are now with COVID. He also advised cleaning and disinfecting houses, and household goods (or burning if replaceable), in addition to the contemporary practice of disinfecting newly arrived cargo. This was accomplished by fire or exposure to the wind, among others. However, the common practice of killing cats in response to plague was likely counterproductive, as rats hosted plague-carrying fleas.

Nevertheless, Angelero’s work was ahead of its time, and helped lay the foundations of modern disease control.

.Source: BBC Future

Categories : Diseases, Syndromes and Conditions T-cellsTags :

Ginger Promising in Countering Autoimmune Diseases

On By ModernMedia

A pre-clinical study has shown that the common herbal remedy and condiment, ginger, may be effective in countering some autoimmune disease mechanisms.

It is already known that ginger has some anti-inflammatory and anti-oxidative properties, making it a popular herbal remedy for inflammatory conditions.Out of at least 14 bioactive compounds, 6-gingerol, which also gives it its distinctive aroma and taste, is reported by a news study to be therapeutic in countering certain autoimmune disease mechanisms in mice.
In mice with antiphospholipid syndrome or lupus, 6-gingerol inhibited the release of neutrophil extracellular traps, which is triggered in response to the autoantibodies produced by these diseases. 

“Neutrophil extracellular traps, or NETs, come from white blood cells called neutrophils,” said lead author Ramadan Ali, PhD. “These sticky spider-web like structures are formed when autoantibodies interact with receptors on the neutrophil’s surface.”

According to Ali, these webs play an important role in the pathogenesis of lupus and antiphospholipid syndrome where they trigger autoantibody formation and contribute to blood vessel clotting and damage.

The premise of the study was: “Will the anti-inflammatory properties of ginger extend to neutrophils, and specifically, can this natural medicine stop neutrophils from making NETs that contribute to disease progression?”
“This pre-clinical study in mice offers a surprising and exciting, ‘yes’,” Ali said.

The researchers discovered that after giving 6-gingerol, the mice had lower levels of NETs. Clot formation tendency was drastically reduced and 6-gingerol seemed to inhibit neutrophil enzymes called phosphodiesterases, in turn lowering neutrophil activation.

All of the mice had reduced autoantibodies, suggesting a disruption of the inflammatory cycle of autoantibodies stimulating NETs which stimulate more autoantibodies.

Study author and rheumatologist Jason Knight, MD, noted that patients often asked about herbal supplements, about which he had not been taught much. However, the pre-clinical trial results show that 6-gingerol has anti-neutrophil properties that may be protective against autoimmune disease progression.

“As for basically all treatments in our field, one size does not fit all. But, I wonder if there is a subgroup of autoimmune patients with hyperactive neutrophils who might benefit from increased intake of 6-gingerol,” said Knight. “It will be important to study neutrophils before and after treatment so we can determine the subgroup most likely to see benefit.”
For a patient with active antiphospholipid syndrome or lupus, the bioactive compound cannot be the primary therapy, but the natural supplement may help those at high risk for disease development.

“Those that have autoantibodies, but don’t have activated disease, may benefit from this treatment if 6-gingerol proves to be a protective agent in humans as it does in mice,” Ali said.

“Patients with active disease take blood thinners, but what if there was also a natural supplement that helped reduce the amount of clots they produce? And what if we could decrease their autoantibodies?”

Source: Medical Xpress

Journal Information: Ramadan A. Ali et al, Anti-neutrophil properties of natural gingerols in models of lupus, JCI Insight (2020). DOI: 10.1172/jci.insight.138385