Category: Diseases, Syndromes and Conditions

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Discovery of Cell Type Linked to Skin Conditions

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Source: NCI on Unsplash

Researchers have found a cell type in human skin that contributes to inflammatory skin diseases such as atopic dermatitis (AD) and psoriasis (PSO). Their study findings were published in the Journal of Experimental Medicine. The team hails from A*STAR’s Singapore Immunology Network (SIgN).

Chronic inflammatory skin diseases such as AD and PSO are characterised by the presence of an activated T cell subtype which secretes pro-inflammatory cytokines in the skin. This immune dysregulation mediated by T cells is central to the pathogenesis of a wide range of inflammatory skin diseases. Thus, understanding the factors modulating T cell priming and activation in healthy and diseased skin is key to developing effective treatments for these diseases.

Recently, a single-cell RNA sequencing (RNA-seq) approach has been used to analyse immune cells in human skin, including dendritic cells (DCs) and macrophages, which are cells that can T cell activation. To tease out the role of DCs and macrophages in chronic inflammatory skin diseases, the team used a combination of complex approaches to yield an unbiased profile/ landscape of DCs and macrophages, and to describe their distinct molecular signatures and proportions in skin lesions of AD and PSO patients.

The researchers found an increase in the proportion of CD14+ DC3s in PSO lesional skin, where they were one of the major cell types co-expressing IL1B and IL23A, two cytokines essential for PSO pathogenesis. This finding suggests that targeting CD14+ DC3 might represent a novel therapeutic option in the treatment of PSO, and demonstrates the potential for the single-cell myeloid cell landscape database to provide important insights into skin biology in health and disease.

Last author Dr Florent Ginhoux, Senior Principal Investigator, SIgN said: “The findings from this study are significant as it will allow the design of new strategies to target or modulate myeloid cell populations for better health outcomes for patients of atopic dermatitis and psoriasis.”

“The roles of antigen-presenting cells in the development of inflammatory skin diseases remain unclear. This study clearly revealed the functions of each antigen-presenting cell subset, which is very informative and valuable to understand the pathogenesis of atopic dermatitis and psoriasis. We expect that this study will lead to the design of new treatment for refractory inflammatory skin diseases.” said Prof Kenji Kabashima, Adjunct Principal Investigator from SIgN and SRIS.

Source: EurekAlert!

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Immune System Mutation Found in Tree-man Syndrome

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Cryo-electron microscopy structure of the human papillomavirus. Source: Wikimedia Commons CC0

A new study explores why some extremely rare cases of human papilloma virus (HPV) infections cause horn-like growths on the skin, a condition known as tree-man syndrome. 

Infection with HPV is extremely common, with most people catching it at some point and not even being aware of it due to a robust immune response, though some may experience skin or genital warts. Why only a handful of individuals react to it by developing tree-man syndrome was not well understood.

To find out why this strikes a handful and not others, Rockefeller’s Jean-Laurent Casanova examines the genetics of an otherwise healthy patient who contracted a severe case of tree-man syndrome and several family members who exhibited milder reactions to HPV. Casanova’s team identified a mutation that affects one’s reaction to HPV by decreasing the production of CD28, a molecule within the immune system that plays an important role in activating pathogen-fighting T cells.

Given the purported importance of CD28 to the immune system, the scientists were surprised that this CD28-deficient individual was healthy prior to contracting tree-man syndrome. “CD28 is thought of as a pillar of T cell immunity,” says Casanova. “The fact that this patient was otherwise healthy suggests that CD28 is largely redundant in human health. Something else is able to step up to provide protection against other infections.”

The findings, published in Cell, form a small part of Casanova’s larger work, which continues to demonstrate that the severity of  influenza, tuberculosis, COVID, and other diseases, is not solely dependent on the pathogen itself, but on genetics of the host, too.

Source: Rockerfeller University

Categories : Diseases, Syndromes and Conditions PoliticsTags :

Rare Diseases in South Africa: A Neglected Topic

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Source: Pixabay/CC0

An article in Spotlight examines the challenges faced by South Africans with rare diseases.

A rare disease is a health condition affecting a small number of people compared with other diseases commonly identified in the population. According to the World Health Organization (WHO), there are between 5000 and 8000 known rare diseases worldwide, affecting an estimated 400 million people.

According to the advocacy group Rare Disease South Africa (RDSA), about 3.6 million people in SA have a rare disease. In South Africa, the ability to diagnose a rare disease is hindered by a lack of capacity and resources, according to research, putting the time to diagnosis for rare diseases in general higher than the estimated 5.5 to 7.5 years in high-income countries.
“There is still low recognition of genetic disorders among specialists. And when they are recognised, testing remains expensive and requires sophisticated levels of training which are relatively limited,” says Prof Karen Fieggen, a medical geneticist at the University of Cape Town (UCT).

According to her, costs, skills, training, and human resource factors are all barriers to effective testing and diagnosis. But she says the rationale to build an effective system is solid.

“We have capable people and expertise to build this system, but until you invest in it, it won’t be big enough to be self-sustaining,” she says.

Prof Fieggen acknowledges that resources are stretched in the public sector, where specialists who carry out genetic testing for rare diseases must meet the needs of a larger part of the population. However, she notes, “there’s no guarantee you’re better off in the private sector”.

“There are very few genetic referral options, and none of the medical geneticists are kept in work full time,” she says. In Cape Town, for example, she says that all patients seeking genetic testing had to come to the private sector until recently. “We have the capacity to train seven specialists a year, but posts aren’t available for them to take,” she says.

At one per 4.5 million population, available medical geneticists in the public healthcare sector fall far short of the 21 per 2 million recommended by the WHO. These services are also spread unevenly through the country. The country’s heavy burden of HIV and TB is partly responsible for this lack of coverage.

While healthcare training must focus on these public health needs, Prof Fieggen says rare diseases need a sensible approach. “It doesn’t help to throw huge resources at something that will have minimal management impact,” she says. “But the way in which rare diseases have been relatively ignored isn’t constructive.”

Helping the recognition of rare diseases and referral pathways in physician training may make a difference. “One thing that could be instilled in training is to recognise that if things are atypical in their presentation, there should be a discussion with a referral centre,” says Associate Professor Ian Ross, a senior consultant endocrinologist at UCT and Groote Schuur Hospital.

Only 2.5-5% of rare diseases have approved treatments, some of which are prohibitively expensive.

The most expensive drug in the world is Zolgensma (generic name onasemnogene abeparvovec), a once-off treatment costing a mind-blowing USD $2.1 million (R 30m). Used to treat inherited spinal muscular atrophy, where infants with the condition are unlikely to see their second birthday. However, even this is available through the UK’s National Health Service, which struck a deal to bring prices down.

Du Plessis says these drugs are not on the essential medicines list because of the small group of patients they would serve. “The essential medicines list is dedicated to treatments that are procured in large numbers. Rare diseases will never be mass-market drugs.”

Such drugs can be purchased by hospital pharmacists so they can be available at a certain hospital, making for a haphazard situation.
To help address this inequality, RDSA held a Rare Disease Symposium on 25 August, inviting feedback on a draft policy framework from various medical sector and political stakeholders.

The framework has a definition for rare disease in SA, namely a condition affecting one in 2000 people or fewer. It also recommends including rare diseases in the NHI benefit package. The NHI bill also includes a Benefits Advisory Committee, which will determine what diseases get coverage,

However, Dr Nicolas Crisp, Acting Director General for Health, said that the NHI would not ring-fence funding. As medical insurance will be done away with, it will be crucial to secure funding for those extremely expensive drugs unaffordable to the private sector.

Source: Spotlight

Categories : Diseases, Syndromes and Conditions Medical IndustryTags :

Review Looks at The Evidence for Cannabis in Paediatric Epilepsies

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Photo by Crystalweed Cannabis on Unsplash

A review published in Developmental Medicine & Child Neurology investigates the knowledge base of cannabis-based medicinal products in paediatric epilepsies, highlighting areas in need of additional research.

Following reports in the media of children with epilepsies apparently deriving benefits from medical marijuana (or cannabis-based medicinal products) accessed abroad, the UK government allowed clinicians to prescribe these products. A previous review found that there was some benefit in certain drug-resistant epilepsies in children.

In the review, the authors also looked at the prescribing environment surrounding these products. They found that the major obstacle to prescribing is a lack of quality evidence for efficacy and safety.
The authors stress that unlicensed cannabis-based medicinal products should not circumvent the usual regulatory requirements before being prescribed. They are also concerned that children with epilepsy are at risk of being exploited as a “Trojan horse” for the cannabis industry, with widespread acceptance of medicinal cannabis accelerating the wider legalisation of marijuana and opening up a highly lucrative commercial market.

Source: News-Medical.Net

Categories : Diseases, Syndromes and Conditions General InterestTags :

September 7 is the First World Field Epidemiology Day

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Photo by Kyle Glenn on Unsplash

In honour of field epidemiologists across the globe, the Training Programs in Epidemiology and Public Health Interventions Network (TEPHINET) has declared 7 September 2021 #WorldFieldEpidemiologyDay.

This day, the first of its kind, is aimed at recognising and raising awareness of the invaluable role Field Epidemiologists play.

As health systems face increasingly complex threats, training workers in field epidemiology is even more important.. The NICD, a division of the National Health Laboratory Service, embarked on a joint collaboration more than 15-years ago in establishing the South African Field Epidemiology Training Programme (SAFETP).  To date the program has trained 98 epidemiologists with the majority located in the public service in South Africa.

Field Epidemiologists, or ‘disease detectives’ are considered the cornerstone of public health preparedness and response. They undertake arduous, time-consuming tasks that include contact tracing, case investigations, community engagement, data collection and analysis.

One such ‘disease detective’ is Alain Musaka Abera, whose team was deployed to Equateur province in the DRC in response to an outbreak of Ebola virus disease (EVD). “The health zone of Ingende had already reported seven confirmed cases, including two deaths in the community,” said Abera, describing his work. “I had to set up the different pillars of epidemiological surveillance (management of alerts, active research, investigation, follow-up of contacts) and, at the same time, support coordination of the response in the health zone.

“The task was tough; the means of transport insufficient; communication almost non-existent. It was necessary to travel long distances in the forest on motorcycles that sometimes broke down and to cross the river in a canoe to search for and investigate suspects. It took courage, determination, and will to face these constraints.”

Source: NICD

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Use of Nicotine-containing E-cigarettes Increases Blood Clot Formation

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Photo by Toan Nguyen on Unsplash

A new study found the use of e-cigarettes containing nicotine has a number of immediate effects, which include increased blood clot formation, blood vessel dysfunction, as well as raised heart rate and blood pressure.

These effects are similar to smoking traditional cigarettes with heart attack or stroke risk with long-term use, according to researchers. The study was presented at the ERS International Congress by Gustaf Lyytinen, a clinician at Helsingborg Hospital and researcher at the Karolinska Institute in Stockholm, Sweden. 

Each of the 22 occasional smoker volunteers was tested before and after taking 30 puffs from an e-cigarette with nicotine, and before and after 30 puffs from an e-cigarette without nicotine. These two sets of tests were conducted on separate occasions, at least one week apart.

On each occasion, the researchers measured volunteers’ heart rate and blood pressure and took a blood sample before they used the e-cigarettes, then 15 minutes after use and again 60 minutes after use. A laser was used to measure dilation of skin blood vessels before volunteers used e-cigarettes and 30 minutes afterwards.
E-cigarettes with nicotine caused an immediate short-term change: a 23% average increase in blood clots after 15 minutes, that returned to normal levels after 60 minutes. Average heart rates also increased from 66bpm to 73bpm. as did blood pressure from 108mmHg to 117mmHg. Researchers observed temporary narrowing of blood vessels after nicotine-containing e-cigarettes use.

These effects were not observed after volunteers used e-cigarettes without nicotine. Nicotine is known to raise levels of hormones including adrenaline, which can increase blood clot formation.

Dr Lyytinen said: “Our results suggest that using e-cigarettes that contain nicotine have similar impacts on the body as smoking traditional cigarettes. This effect on blood clots is important because we know that in the long-term this can lead to clogged up and narrower blood vessels, and that of course puts people at risk of heart attacks and strokes.”

Source: European Respiratory Society

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Abrocitinib Promising in Teen Atopic Dermatitis

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Credit: National Institute of Allergy and Infectious Diseases, National Institutes of Health

Following treatment with the investigational oral Janus kinase (JAK) inhibitor abrocitinib plus topical therapy, teenagers with moderate or severe atopic dermatitis (AD) showed significant improvement to placebo, according to a new study published in JAMA Dermatology.

Up to 20% of children and adolescents are affected by AD, which has an adverse impact on QoL, academic performance, and social relationships, as well as the QoL of caregivers. Subcutaneous dupilumab is safe and effective in moderate-to-severe AD in adolescents, but there is a lack of an oral option, they said.

Nearly half of the patients had clear or almost clear skin by clinician assessment (IGA), and about 70% of patients treated with either of two doses of the JAK inhibitor had at least 75% improvement in the Eczema Area and Severity Index (EASI-75). In contrast, a fourth of patients who received placebo in addition to topical therapy met the clinician assessment outcome and about 40% met EASI-75 criteria.

Abrocitinib, a JAK-1-selective inhibitor, had already shown to be tolerable and effective in adults. The present trial included 285 patients aged 12 to 17, with coprimary endpoints being an IGA score of 0/1 with at least a two-grade improvement from baseline, plus an EASI-75 response, with both outcomes assessed at 12 weeks. Secondary endpoints included improvement in pruritis.

An IGA 0/1 response was seen in 46.2% of patients treated with abrocitinib 200 mg and 41.6% of those assigned to abrocitinib 100 mg, compared to 24.5% in the placebo group. The proportion of patients who met EASI-75 response criteria was 72% with abrocitinib 200 mg, 68.5% with abrocitinib 100 mg, and 41.5% with placebo. Significant improvement was seen in pruritis compared to placebo, showing an improvement in pruritis. The researchers noted that improved indicators could lead to better sleep and QoL indicators.

AE rates were 62.8% with the higher dose of abrocitinib, 56.8% with the lower dose, and 52.1% in the placebo group, with nausea occurring more often with abrocitinib 200 mg than with abrocitinib 100 mg (18.1% vs 7.4%).

These results suggest abrocitinib has great potential for treating teenage AD, said John C. Browning, MD, of Texas Dermatology and Laser Specialists in Dallas. Current there are no JAK inhibitors indicated for AD, and an oral option is very exciting he to MedPage Today via email. “Not everyone responds to current systemic therapies, so there is a definite need for new treatments.”

“I think more teens will be open to trying an oral option, but they will need to be committed to taking it every day,” he said, adding that compliance is an issue. “Both abrocitinib and dupilumab are effective, so there is not a tradeoff in going from injections to oral therapy.”

Source: MedPage Today

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Another COVID-scale Pandemic in 59 Years ‘Statistically Likely’

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Photo by Edwin Hooper on Unsplash

A new study based on 400 years of historical records asserts that extreme pandemic events such as COVID are more common than believed.

The Duke University study, published in Proceedings of the National Academy of Sciences, used records of past outbreaks to estimate the intensity of those events and the yearly probability of them recurring.

It found the probability of a pandemic with similar impact to COVID is about 2% in any year, meaning that someone born in the year 2000 by now would have about a 38% chance of experiencing one. That probability is only increasing, highlighting the need to adjust perceptions of pandemic risks and expectations for preparedness, the researchers said.

“The most important takeaway is that large pandemics like COVID and the Spanish flu are relatively likely,” said study co-author William Pan, PhD, associate professor of global environmental health at Duke. The understanding that pandemics are not so rare should raise the priority of future prevention and control efforts, he said.

The study employed new statistical methods to measure the scale and frequency of disease outbreaks for which there was no immediate medical intervention over the past four centuries. Their analysis, including deadly pathogens including plague, smallpox, cholera, typhus and novel influenza viruses, found pandemics occurred with great variability in the past. But they also identified patterns that allowed them to describe the probabilities of similar-scale events happening again.

In the case of a pandemic like the Spanish flu, which killed more than 30 million people between 1918 and 1920, the probability of a pandemic of similar magnitude occurring ranged from 0.3% to 1.9% per year over the time period studied. Taken together, it is statistically likely that such a massive pandemic would occur within the next 400 years.

However, the data also show that the risk of intense outbreaks is increasing rapidly. Based on the increasing rate at which novel pathogens such as SARS-CoV-2 have broken loose in human populations in the past 50 years, the study estimates that the probability of novel disease outbreaks will likely triple in the next few decades.

With this increased risk factor, the researchers estimate that a COVID-scale pandemic is likely within a span of 59 years (by the year 2090), a result they write is “much lower than intuitively expected.” Although not included in the paper, they also calculated the probability of a pandemic capable of eliminating all human life, finding it statistically likely within the next 12 000 years. 

That does not mean it will be 59 years before the next COVID-like pandemic, nor that the Spanish flu for another 300 years. Such events are equally probable in any year during the span, said Duke University Professor Gabriel Katul, another of the paper’s authors.

“When a 100-year flood occurs today, one may erroneously presume that one can afford to wait another 100 years before experiencing another such event. This impression is false. One can get another 100-year flood the next year,” explained Prof Katul.

Dr Pan noted that population growth, changes in food systems, environmental degradation and more frequent contact between humans and disease-harboring animals all may be significant factors for increasing frequency of pandemics. However, he stresses that the statistical techniques are not to explain the pandemics.

However, he hopes the study will spark deeper exploration of the factors that may be making devastating pandemics more likely – and how to counteract them.

“This points to the importance of early response to disease outbreaks and building capacity for pandemic surveillance at the local and global scales, as well as for setting a research agenda for understanding why large outbreaks are becoming more common,” Dr Pan said.

Source: Duke University

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New Evidence-based Resources to Aid Plaque Psoriasis Treatment Decisions

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Source: CC0 Creative Commons

The Targeted Therapies Alliance has made a range of evidence-based resources available to help dermatologists and their patients in shared decision making in the treatment of plaque psoriasis.

Psoriasis, of which plaque psoriasis is the most common type, is the most prevalent immune-mediated inflammatory disease. It involves skin and in some cases, joints, and can be associated with abnormalities of other systems.

NPS MedicineWise spokesperson Jonathan Dartnell said: “While the condition currently does not have a cure, it can be well controlled, hence there is a need to support people with plaque psoriasis to understand and follow the treatment to get the best results.”

“The members of the Targeted Therapies Alliance have worked closely with the Australasian College of Dermatologists and Psoriasis Australia to create these resources which were developed with input from consumers with plaque psoriasis,” he said.

Australasian College of Dermatologists Fellow A/Prof Stephen Shumack said the resources were developed through a collaborative effort.

Jonathan Dartnell, Spokesperson, NPS MedicineWise said: “These resources were designed to support optimal patient outcomes by helping improve understanding of, and adherence to, the treatments for plaque psoriasis. The resources cover topical treatments such as creams and ointments, to phototherapy and systemic treatments.”

The new resources available include:

  • A consumers’ fact sheet with an overview of the topical treatment options (such as creams and ointments) and questions to ask their doctor to make sure they understand why, how and when to use their topical treatments.
  • A decision aid to help consumers speak to their doctor about treatment options should topical treatments not be enough.
  • An action plan and information to address some myths and help adherence to low-dose methotrexate.

The new dermatology resources complement existing Targeted Therapies Alliance resources focused on gastroenterological and rheumatological conditions. They also are part of a wider three-year programme to ensure the best possible health and economic outcomes from the use of biological and other specialised medicines.

Source: News-Medical.Net

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Human Transmission in Antibiotic-resistant Plague Outbreak

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Scanning electron micrograph of Yersinia pestis, which causes bubonic plague, on proventricular spines of a Xenopsylla cheopis flea.
 
Credit: National Institute of Allergy and Infectious Diseases/NIH


Analysing a recent outbreak of plague in Madagascar, a team of researchers uncovered evidence of human transmission of antimicrobial-resistant plague.

While COVID dominates the global awareness of infectious diseases, others are still out there, such as Yersinia pestis, which causes plague. Even though plague has been largely eradicated in the developed world, hundreds of people globally contract it each year.

When a human is infected with bubonic plague from a flea bite and it goes untreated, the infection can progress, spread to the lungs and resulting in pneumonic plague. Pneumonic plague is usually lethal if not treated quickly, and infected patients can transmit the disease to others via respiratory droplets. A team of scientists from Northern Arizona University’s Pathogen and Microbiome Institute, led by professor Dave Wagner, recently published their findings from a remarkable study involving antimicrobial resistant (AMR) plague.

Plague is considered to be a reemerging and neglected disease, particularly in the East African island country of Madagascar, which reports the majority of annual global cases. There is no vaccine for it, so preventing mortality from plague requires rapid diagnosis followed by antibiotic treatment. In Madagascar, the antibiotic streptomycin is usually the first-line treatment for plague. The researchers isolated a streptomycin-resistant AMR strain of Y. pestis from a pneumonic plague outbreak that occurred there in 2013, involving 22 cases, including three fatalities. The study was recently published in Clinical Infectious Diseases.

“By characterising the outbreak using epidemiology, clinical diagnostics and DNA-fingerprinting approaches,” Prof Wagner said, “we determined—for the first time—that AMR strains of Y. pestis can be transmitted person-to-person. The AMR strain from this outbreak is resistant to streptomycin due to a spontaneous point mutation, but is still susceptible to many other antibiotics, including co-trimoxazole. Luckily, the 19 cases that were treated all received co-trimoxazole in addition to streptomycin, and all of them survived.

“The point mutation, which also is the source of streptomycin resistance in other bacterial species, has occurred independently in Y. pestis at least three times and appears to have no negative effect on the AMR strain, suggesting that it could potentially persist in nature via the natural rodent-flea transmission cycle. However, AMR Y. pestis strains are exceedingly rare and the mutation has not been observed again in Madagascar since this outbreak.”

Source: North Arizona University