Category: Diseases, Syndromes and Conditions

Categories : Diseases, Syndromes and ConditionsTags :

Asymptomatic Detection of Monkeypox Suggests it is More Widespread

On By ModernMedia
Colourised transmission electron micrograph of monkeypox virus particles (green) cultivated and purified from cell culture. Credit: NIAID

A brief research report in Annals of Internal Medicine documents positive monkeypox virus PCR results found in anal samples taken from asymptomatic MSM (men who have sex with men). These findings suggest that vaccination limited to those with known exposure to the monkeypox virus may not be an effective strategy for preventing infection.

The findings come as the World Health Organization has renamed the variants, or clades, of monkeypox from their previous geographically-derived names to Roman numerals, eg, the former Congo Basin (Central African) clade is now Clade one (I). It is also seeking inputs on a possible new name for the virus in order to avoid stigmatisation.

Researchers from Bichat–Claude Bernard Hospital, Paris, retrospectively performed testing for monkeypox virus on all anorectal swabs that were collected as part of a sexually transmitted infection screening program. This type of screening is performed every three months among MSM with multiple sexual partners who are either taking HIV preexposure prophylaxis (PrEP) or living with HIV and receiving antiretroviral treatment. Of the 200 asymptomatic persons screened that were negative for N. gonorrhoeae and C. trachomatis, 13 (6.5%) samples were PCR positive for monkeypox virus.  Two of the 13 later developed symptoms of monkeypox.

While it is not know whether asymptomatic transmission will play a role in the current worldwide monkeypox epidemic and the mode of human-to-human transmission may provide evidence that asymptomatic or preclinical spread can occur. In an accompanying editorial, Stuart N. Isaacs, MD, at the University of Pennsylvania, suggests that an expanded ring vaccination strategy and other public health interventions in the highest-risk communities are likely needed to help control the outbreak. 

Source: EurekAlert!

Categories : Diseases, Syndromes and ConditionsTags :

A Breakthrough Tinnitus Therapy – on a Smartphone

On By ModernMedia
Photo by Dylann Hendricks | 딜란 on Unsplash

After 20 years searching for a cure for tinnitus, for which there is no pharmacological treatment, there are ‘encouraging results’ from a clinical trial of a smartphone app therapy, the results of which have been published in Frontiers in Neurology.

The study randomised 61 patients to one of two treatments, the prototype of the new ‘digital polytherapeutic’ or a popular self-help app producing white noise. On average, the group with the polytherapeutic (31 people) showed clinically significant improvements at 12 weeks, while the other group (30 people) did not.

“This is more significant than some of our earlier work and is likely to have a direct impact on future treatment of tinnitus,” said Associate Professor in Audiology at the Universirt of Auckland, Dr Grant Searchfield.

Key to the new treatment is an initial assessment by an audiologist who develops the personalised treatment plan, combining a range of digital tools, based on the individual’s experience of tinnitus.

“Earlier trials have found white noise, goal-based counselling, goal-oriented games and other technology-based therapies are effective for some people some of the time,” says Dr Searchfield.

“This is quicker and more effective, taking 12 weeks rather than 12 months for more individuals to gain some control.”

“What this therapy does is essentially rewire the brain in a way that de-emphasises the sound of the tinnitus to a background noise that has no meaning or relevance to the listener,” Dr Searchfield says.

Audiology research fellow Dr Phil Sanders says the results are exciting and he found running the trial personally rewarding.

“Sixty-five percent of participants reported an improvement. For some people, it was life-changing – where tinnitus was taking over their lives and attention.”

Some people didn’t notice an improvement and their feedback will inform further personalisation, Dr Sanders noted.

Tinnitus is a phantom noise and its causes are complex. It has so far defied successful treatment.

While most people experience tinnitus, or ringing in the ears at least on occasions, around five percent experience it to a distressing degree. Impacts can include trouble sleeping, difficulty carrying out daily tasks and depression.

Dr Searchfield says seeing his patients’ distress and having no effective treatment to offer inspired his research. “I wanted to make a difference.”

The next step will be to refine the prototype and proceed to larger local and international trials with a view to FDA approval.

The researchers hope the app will be clinically available in around six months.

Source: University of Auckland

Categories : Diseases, Syndromes and ConditionsTags :

Chronic Inflammation Link to Low Vitamin D Explains Some Controversies

On By ModernMedia
Vitamin D pills
Photo by Michele Blackwell on Unsplash

New genetic research shows a direct link between low vitamin D levels and high levels of inflammation, providing an important biomarker to identify people at higher risk of or severity of chronic illnesses with an inflammatory component, such as type 2 diabetes. The findings, published in the International Journal of Epidemiology, also helps to settle some of the controversies surrounding the ‘sunshine vitamin’.

The study drew on genetic data for 294 970 participants in the UK Biobank, using Mendelian randomisation to show the association between vitamin D and C-reactive protein levels, an indicator of inflammation.

University of South Australia’s Dr Ang Zhou, the study’s lead researcher, said that the findings suggest that boosting vitamin D in people with a deficiency may reduce chronic inflammation.

“This study examined vitamin D and C-reactive proteins and found a one-way relationship between low levels of vitamin D and high levels of C-reactive protein, expressed as inflammation.

“Boosting vitamin D in people with deficiencies may reduce chronic inflammation, helping them avoid a number of related diseases.”

The study also raises the possibility that having adequate vitamin D concentrations may mitigate complications arising from obesity and reduce the risk or severity of chronic illnesses with an inflammatory component, such as CVDs, diabetes, and autoimmune diseases.

Senior investigator and Director of UniSA’s Australian Centre for Precision Health, Professor Elina Hyppönen, said that these results offer an explanation for some of the controversies in reported associations with vitamin D.

“We have repeatedly seen evidence for health benefits for increasing vitamin D concentrations in individuals with very low levels, while for others, there appears to be little to no benefit.” Prof Hyppönen said.

“These findings highlight the importance of avoiding clinical vitamin D deficiency, and provide further evidence for the wide-ranging effects of hormonal vitamin D.”

Source: University of South Australia

Categories : Diseases, Syndromes and ConditionsTags :

What Antivirals are Suitable for Monkeypox Treatment?

On By ModernMedia
Colourised transmission electron micrograph of monkeypox virus particles (green) cultivated and purified from cell culture. Credit: NIAID

In light of the recent spread of monkeypox virus, now declared a public health emergency of international concern by the World Health Organization, there is a need for treatments. In an article published in Clinical Infectious Diseases, authors review three antiviral agents with activity against monkeypox: cidofovir, brincidofovir, and tecovirimat.

Human monkeypox, caused by the monkeypox virus, a member of the genus Orthopoxvirus within the Poxviridae family of double-stranded DNA (dsDNA) viruses, was first described in a baby in the Democratic Republic of Congo in 1970. Since then, it has resulted in multiple outbreaks in Central and West Africa, and occasionally in Europe and North America. Human-to-human transmission in households has been reported, especially among those unvaccinated against smallpox.

Cidofovir
Although cidofovir has broad activity against many DNA viruses including orthopoxviruses, it is only FDA approved for the treatment of cytomegalovirus retinitis. Cidofovir (CDV) is a prodrug, which must first enter host cells, where it is converted into the active form, CDV diphosphate (CDV-pp). CDV-pp has a prolonged intracellular half-life, and slows viral DNA replication by being incorporated into the growing DNA strand. Pharmokinetics suggest poor oral absorption and is available as intravenous infusions.

In humans, CDV has been used to treat ocular cowpox and as a topical treatment for molluscum cantiogosum.

Brincidofovir
Brincidofovir (BCV) is a lipid-conjugated CDV analogue, FDA-approved in 2021 for the treatment of smallpox. Like CDV, BCV has broad activity against dsDNA viruses. It can be be taken up by the small intestines, and unlike CDV, which slowly crosses cellular membranes, brincidofovir readily enters host cells due to its lipophilicity. Inside cells, BCV is converted into CDV and then CDV-pp. CDV-pp reaches higher intracellular concentrations after BCV administration due to its ability to cross cellular membranes more efficiently. Like CDV, BCV has a prolonged intracellular half-life and inhibits viral replication.

In prairie dog models, which exhibit similarity to the human course, BCV improved survival when administered shortly after infection, suggesting that early treatment is important.

Tecovirimat
Tecovirimat was FDA approved in 2018 for the treatment of smallpox, and has activity against orthopoxviruses, but has no notable activity against other dsDNA viruses. Tecovirimat targets a gene which encodes for membrane protein p37, responsible for the formation of extracellular enveloped virus.

The oral route results in better absorption for tecovirimat, and is effective against monkeypox virus in macaques and prairie dogs. Administration within 72 hours of exposure to poxvirus reduced lesion severity and mortality in various animal models.

Tecovirimat synergises with BCV, and was successfully used to treat monkeypox in two human cases.

Conclusion
The authors note that while CDV and BCV inhibit DNA replication, tecovirimat is more specific to orthopoxviruses and prevents enveloped virus formation, stalling cell-cell transmission.

BCV and tecovirimat could be promising therapeutic candidates based on their tolerability profiles, they conclude. More studies are needed to identify those most at risk from monkeypox and establish the optimal initiation time and duration for therapy.

Categories : Diseases, Syndromes and ConditionsTags :

HSV-1 Driven by Ancient Migrations – and Introduction of Kissing

On By ModernMedia
Photo by Cottonbro on Pexels

The HSV-1 virus strain behind facial herpes, commonly known as cold sores, emerged approximately 5000 years ago, according to University of Cambridge-led research published in Science Advances. The virus arose in the wake of vast Bronze Age migrations into Europe from the Steppe grasslands of Eurasia, and associated population booms that boosted transmission.

Two-thirds of the world’s population below the age of 50 now carry HSV-1, manifesting as occasional lip sores. In combination with other ailments – sepsis or even COVID, for example – the virus can be fatal. In 2018, two women died of HSV-1 infection in the UK following Caesarean births.

Herpes has an ancestry dating back millions of years, infecting species from bats to coral. Despite being prevalent among humans today, however, scientists say that ancient examples of HSV-1 were surprisingly hard to find.

According to the study authors of the study, , the Neolithic flourishing of facial herpes detected in the ancient DNA may have coincided with the advent of a new cultural practice imported from the east: romantic and sexual kissing.    

“Facial herpes hides in its host for life and only transmits through oral contact, so mutations occur slowly over centuries and millennia,” said Dr Charlotte Houldcroft, co-senior author.

“We need to do deep time investigations to understand how DNA viruses like this evolve. Previously, genetic data for herpes only went back to 1925.”

The team managed to hunt down herpes in the remains of four individuals stretching over a thousand-year period, and extract viral DNA from the roots of teeth. Herpes often flares up with mouth infections: at least two of the ancient cadavers had gum disease and a third smoked tobacco.

The oldest sample came from an adult male excavated in Russia’s Ural Mountain region, dating from the late Iron Age around 1500 years ago.

Two further samples were local to Cambridge, UK. One a female from an early Anglo-Saxon cemetery a few miles south of the city, dating from 6-7th centuries CE. The other was a young adult male from the late 14th century who had suffered appalling dental abscesses. 

The final sample came from a young adult male excavated in Holland: a fervent clay pipe smoker, most likely massacred by a French attack on his village by the banks of the Rhine in 1672. 

“We screened ancient DNA samples from around 3000 archaeological finds and got just four herpes hits,” said co-lead author Dr Meriam Guellil, from Tartu University’s Institute of Genomics.

“By comparing ancient DNA with herpes samples from the 20th century, we were able to analyse the differences and estimate a mutation rate, and consequently a timeline for virus evolution,” said co-lead author Dr Lucy van Dorp, from the UCL Genetics Institute.     

Co-senior author Dr Christiana Scheib said: “Every primate species has a form of herpes, so we assume it has been with us since our own species left Africa.”

“However, something happened around five thousand years ago that allowed one strain of herpes to overtake all others, possibly an increase in transmissions, which could have been linked to kissing.”

The first known report of kissing is a Bronze Age manuscript from South Asia, and suggest the custom, not found in most human cultures, may have travelled westward with migrations into Europe from Eurasia.   

In fact, centuries later, the Roman Emperor Tiberius tried to ban kissing at official functions to prevent disease spread, a decree that may have been herpes-related.

However, for most of human prehistory, HSV-1 transmission would have been ‘vertical’: passing from infected mother to newborn child.

Source: University of Cambridge

Categories : Diseases, Syndromes and Conditions Healthcare Politics and RegulationsTags :

Despite Disagreement, WHO Sounds Highest Alert for Monkeypox

On By ModernMedia
Source: Pixabay CC0

On 22 July, World Health Organisation (WHO) director general Dr Tedros Adhanom Ghebreyesus declared the global spread of monkeypox a Public Health Emergency of International Concern (PHEIC) – a move which went against the recommendation of a special committee. This was the first time since the PHEIC’s inception in 2005 that it had done so. The special committee’s reluctance to recommend a PHEIC has previously drawn criticism from public health experts.

The 21 July meeting of WHO’s Emergency Committee, did not reach a consensus on whether to declare the growing monkeypox outbreak a PHEIC; a narrow majority voting against doing so. But Dr Tedros invoked a PHEIC at a press conference the next day in Geneva. “We have an outbreak that has spread around the world rapidly, through new modes of transmission, about which we understand too little and which meets the criteria in the International Health Regulations,” he said.

Data presented during the meeting including modelling which showed the basic reproduction number (R0) to be above 1 among gay or bisexual men, and below 1 in other groups. For example, in Spain, the estimated R0 is 1.8, in the United Kingdom 1.6, and in Portugal 1.4.

In June, the committee first recommended against declaring a PHEIC , which was roundly criticised by epidemiologists and global health experts. Dr Tedros reconvened the group this week and asked it to reconsider the question. Nine members were against declaring a PHEIC and six in favour, Dr Tedros said at the press conference.

According to Science, the Thursday meeting of the expert panel was followed by tense exchanges via email and text messages between its participants.

One of the objections to a PHEIC was that few deaths had been caused by the disease so far and was not spreading in the general population. Another was that a PHEIC could possibly lead to further stigmatisation of men who have sex with men (MSM), the group primarily affected.

Many gay rights and sexual health advocates were for the PHEIC, as it would help raise awareness and help protect the most at-risk group of MSM.

“Although I’m declaring a public health emergency of international concern, for the moment, this is an outbreak that’s concentrated among men who have sex with men, especially those with multiple sexual partners,” Dr Tedros said. “That means that this is an outbreak that can be stopped with the right strategies in the right groups.”

Those who push for declaring a PHEIC also cited the rising number of monkeypox cases (over 15 000) and the countries affected (70), and that many cases are likely still not being picked up. The virus could also potentially establish itself permanently worldwide – indeed, the CDC reported that two children in the US had been infected.

Sources familiar with the deliberations of the committee said the votes for a PHEIC were driven by those with expertise in monkeypox and LGBT health, and those against by more generalist global heath voices.

According to Science, sources familiar with the committee’s deliberation said that those in favour of a PHEIC had monkeypox and LGBT health expertise, and those against were from a global health standpoint.

While a PHEIC can give the WHO some extra powers, it is the loudest level of alert it can sound. Since its creation in 2005, PHEIC has been declared six times: for outbreaks of H1N1 influenza, polio, Zika, COVID (ongoing), and twice for Ebola outbreaks (one ongoing).

Source: Science.org

Categories : Diseases, Syndromes and ConditionsTags :

Monkeypox Symptoms Described in Case Series

On By ModernMedia
Source: Wikimedia CC0

A large case series on monkeypox was published in The New England Journal of Medicine, which will help direct the limited resources such as vaccines to contain the recent spread of the virus. In the study, clinicians led by Queen Mary University of London identified new clinical symptoms of monkeypox infection, which will aid future diagnosis and help to slow the spread of infection. This is the largest case study series to date, reporting on 528 confirmed monkeypox infections at 43 sites between 27 April and 24 June 2022.

Gay and bisexual men make up 98% of infected persons in the current spread of the virus. While in most cases sexual closeness is the most likely route of transmission, researchers stress that the virus can be transmitted by any close physical contact through large respiratory droplets and potentially through clothing and other surfaces.

There is a global shortage of both vaccines and treatments for human monkeypox infection. The findings of this study, including the identification of those most at risk of infection, will help to aid the global response to the virus. Public health interventions aimed at higher risk of exposure could help to detect and slow the spread of the virus. Recognising the disease, contact tracing and advising people to isolate will be key components of the public health response.  

Many of the infected individuals reviewed in the study presented with symptoms not recognised in current medical definitions of monkeypox. These symptoms include single genital lesions and sores on the mouth or anus. The clinical symptoms are similar to those of sexually transmitted infections (STIs) and can easily lead to misdiagnosis.

In some people, anal and oral symptoms have led to people being admitted to hospital for management of pain and difficulties swallowing. Since misdiagnosis can slow detection, hindering efforts to control the spread of the virus, this information is important for clinicians. This information will help increase diagnoses in persons from at-risk groups present with traditional STI symptoms.

Public health measures – such as enhanced testing and education – should be developed and implemented working with at-risk groups to ensure that they are appropriate, non-stigmatising, and to avoid messaging that could drive the outbreak underground.

Source: Queen Mary University of London

Categories : Diseases, Syndromes and Conditions GeneticsTags :

Once-off Gene Therapy Reduces Haemophilia B Bleeding in Patients

On By ModernMedia
https://www.pexels.com/photo/a-close-up-shot-of-bags-of-blood-4531306/
Photo by Charlie-Helen Robinson on Pexels

A single gene therapy injection could dramatically reduce the bleeding risk faced by people with haemophilia B, according to the results of a Phase I/II clinical trial published in the New England Journal of Medicine.

Low levels of the factor IX (FIX) protein, needed for clot formation, are behind haemophilia B. The FIX protein gene is on the X chromosome, so the severe form of haemophilia B is much more common in men, though it can occur in women due to X chromosome inactivation.

To prevent excessive bleeding, patients with haemophilia B typically need regular replacement therapy consisting of weekly injections of recombinant FIX. Despite advances in treatment, patients may continue to see debilitating joint damage.

The new treatment, from University College London, Royal Free Hospital and biotechnology company Freeline Therapeutics, is a type of adeno-associated virus (AAV) gene therapy candidate, called FLT180a, is being developed to treat severe and moderately severe cases of haemophilia B.

The Phase I/II multi-centre clinical trial, called B-AMAZE, and the related long-term follow up study found that a single treatment with FLT180a led to sustained production of FIX protein from the liver in 9 of 10 patients, across four different dose levels, removing the need for regular replacement therapy.

Out of 17 male patients aged 18 or over who underwent screening, 10 with severe or moderately severe haemophilia B took part in the 26-week trial of FLT180a, will be followed-up to assess safety and durability of FIX expression for 15 years.

Lead author Professor Pratima Chowdary of the Royal Free Hospital said: “Removing the need for haemophilia patients to regularly inject themselves with the missing protein is an important step in improving their quality of life. The long term follow up study will monitor the patients for durability of expression and surveillance for late effects.”

One patient, Elliott Mason, told the BBC: “I’ve not had any treatment since I had my therapy, it’s all a miracle really, well it’s science, but it feels quite miraculous to me.

“My life is completely normal, there’s nothing that I have to stop and think ‘how might my haemophilia affect this?’.”

AAV gene therapy works uses a packaging from the proteins found in the outer coat of the virus to deliver a functional copy of a gene directly to patient tissues. Newly synthesised proteins are released into the blood and a one-time infusion can have long-term effects.

Over several weeks to several months, patients took immunosuppressive drugs to prevent their immune systems from rejecting the therapy, and all reported known side effects.

Though the therapy was well tolerated, patients all experienced adverse events, with an abnormal blood clot in one who received the highest FLT180a dose and had the highest levels of FIX protein.

Professor Amit Nathwani, who co-authored the study, said: “Gene therapy is still a young field that pushes the boundaries of science for people with severe genetic diseases.

“The B-AMAZE long-term data add to the growing body of evidence that gene therapy has the potential to free patients from the challenges of having to adhere to lifelong therapy or could provide treatment where none exists today.”

In nine out of the ten patients, the treatment led to a sustained increase in FIX protein production, which led to a decrease in excessive bleeding. They also no longer required weekly injections of FIX protein.

After 26 weeks, five patients had normal levels of FIX protein, three had low but increased levels, and one patient treated at the highest dose had an abnormally high level.

Pamela Foulds, MD, Chief Medical Officer of Freeline, said: “The B-AMAZE long-term data continue to support our confidence that a single dose of FLT180a could protect people with haemophilia B from bleeding and the need for lifelong FIX replacement through durable expression of FIX at protective levels.”

Source: EurekAlert!

Categories : Diseases, Syndromes and ConditionsTags :

Good Enough: Making an Imperfect Protein for Cystic Fibrosis

On By ModernMedia
Anatomical model of lungs
Photo by Robina Weermeijer on Unsplash

Antisense oligonucleotides (ASOs), are molecules that can be used to control protein levels in cells. Researchers detail in Nature how they leveraged ASO technology to develop the first FDA-approved treatment for spinal muscular atrophy called Spinraza®. The drug has helped over 11 000 patients make more of a protein that certain neurons in the spine need.

Cold Spring Harbor Laboratory Professor Adrian Krainer, who developed the drug, has been searching for more ways ASOs can help treat other disorders. He has identified cystic fibrosis (CF), where patients produce insufficient amount of the protein CFTR. His team discovered how to use ASOs to make more of an imperfect but still functional version of CFTR. This could lead to a new treatment approach that may help alleviate CF symptoms.

The imperfect CFTR protein results from a gene mutation. The faulty instructions to produce the protein are eliminated and the protein isn’t made, since in general, imperfect proteins may be disruptive. Prof Krainer’s ASOs trick cells into following the faulty instructions and making the imperfect CFTR protein. His team found that, in this case of CF, having an imperfect version of the protein is better than having none at all. Their method improved the function of lung cells, suggesting the ASO strategy could improve symptoms in CF patients with this mutation.

The team’s discovery spotlights a new way ASOs can be used to treat disease. The study was led by Young Jin Kim, a former MD-PhD student in the Krainer laboratory. Prof Krainer hopes to continue expanding the potential of ASO technology in therapeutics. He thinks in the future ASOs may increasingly become a way to tailor therapies specific to an individual’s unique genetic mutations. “If more of this type of drug, ASOs, are approved,” Prof Krainer said, “I wouldn’t be surprised if in the not-so-distant future ASOs become a routine way to make personalised medicines.”

Source: Cold Spring Harbor Laboratory

Categories : Diseases, Syndromes and Conditions New Compounds and TreatmentsTags :

Two New Antibody Treatments for Crohn’s Disease Equally Effective

On By ModernMedia
Anatomy of the gut
Source: Pixabay CC0

In a clinical trial, two new antibody treatments for Crohn’s disease were approximately similar in effectiveness, according to findings published in The Lancet.

This allows clinicians and patients to make treatment choices based on tolerance, according to Stephen Hanauer, MD, the Clifford Joseph Barborka Professor and a co-author of the study.

“The safety and efficacy of two agents with different mechanisms of action appears to be quite comparable over one year,” said Prof Hanauer.

Crohn’s disease (CD) is a chronic, progressive inflammatory bowel disease, causing abdominal pain, weight loss and fatigue. Treatment has usually focused on alleviating symptoms to achieve clinical remission using corticosteroids or immunomodulators, but more effective treatment is still needed, according to Prof Hanauer.

‘While there are numerous therapies and mechanisms of action for drugs approved for moderate-severe Crohn’s disease there has been a therapeutic ceiling as far as outcomes are concerned, with usually less than 50% of patients in long-term remission,” Prof Hanauer explained.

Recently, several biologic agents have been approved for use. Adalimumab is a monoclonal antibody that reduces inflammatory cytokines by inhibiting tumor necrosis factor alpha. Ustekinumab is another monoclonal antibody, though the drug targets a different set of proteins: interleukin (IL) 12 and IL-23.

Researchers recruited with Crohn’s disease, randomising 191 to receive ustekinumab and 195 to adalimumab. Patients reaching clinical remission were similar between both groups: 65% of 191 patients in the ustekinumab group versus 61% of 195 in the adalimumab group. There were no deaths through one year of study, though slightly more patients in the ustekinumab group discontinued study treatment. Disease severity measures decreased similarly over the study.

Both treatment regimens resulted in clinical remission with similar toxicity profiles.

“There are numerous options for patients with moderate-severe disease. However, the key is to treat patients with an effective regimen and treat to targets as early in the course as possible since we do not have any drugs that impact on fibrosis once it occurs,” Prof Hanauer said.

Source: Northwestern University