Category: Diseases, Syndromes and Conditions

NICD Issues Lassa Fever Alert over KZN Case

Lassa virus scanning electron micrograph
Scanning electron micrograph of Lassa virus budding off a Vero cell. Image credit: National Institute of Allergy and Infectious Diseases, NIH

The National Institute for Communicable diseases has reported that a case of Lassa fever was diagnosed in a man from KwaZulu-Natal on 12 May 2022. The man had extensive travel history in Nigeria before returning to South Africa. He fell ill after entering South Africa and was hospitalised in a Pietermaritzburg hospital. The diagnosis of Lassa fever was confirmed by lab tests. Sadly, the man succumbed to the infection.

Contact tracing and monitoring is underway. No secondary cases of Lassa fever have been confirmed at the time of this report. In February 2022, three cases of Lassa fever had been reported in the UK, with the first travelling from Mali and the other two resulting from secondary transmission.

Originally discovered in 1969, Lassa fever is a rodentborne viral haemorrhagic fever endemic to West African countries and is caused by Lassa virus. Up to 300 000 cases of Lassa fever, with about 5000 deaths, are recorded annually in the endemic countries. Currently there is no vaccine for Lassa fever. The clinical course of Lassa fever is either not recognised or mild in 80% of patients; however, about 20% of patients might experience severe disease, including facial swelling, hepatic and renal abnormalities, pulmonary oedema, and haemorrhage. Although overall case-fatality rates for patients with Lassa fever is about 1%, rates among hospitalised case-patients are >15%. Intravenous administration of the antiviral drug ribavirin has become the standard of care for treatment of Lassa fever, but data on the efficacy of intravenous ribavirin are limited. The original study among Lassa fever patients in Sierra Leone found survival to be significantly higher (p = 0.0002) among those who obtained ribavirin within the first 6 days of illness (55%) compared with those who never received the drug (5%). 

The natural reservoir of this virus in endemic countries is the Mastomys rat. The rats are persistently infected, shedding the virus in their urine and faeces. Humans can come into contact with the virus through direct contact or inhalation of the virus in areas that are infested with the infected rats. For example, contact with contaminated materials, ingestion of contaminated food or inhalation of air that has been contaminated with urine droplets. Person-to-person transmission of the virus does not occur readily and the virus is not spread through casual contact.

Person-to-person transmission is not common and is mostly associated with the hospital-setting where healthcare workers have contact with the infected blood and bodily fluids of a patient. Cases of Lassa fever in travellers returning from endemic countries are reported from time-to-time. In 2007 a case of Lassa fever was diagnosed in South Africa. That case involved a Nigerian citizen with extensive travel history in rural parts of Nigeria before falling ill, and he received medical treatment in South Africa. There were no reported secondary cases of Lassa fever on this occasion. Recently, in February 2022, an imported case of Lassa fever with secondary cases were identified in the United Kingdom.

Source: NICD

Sarin Gas Likely the Cause of Mysterious Gulf War Illness

Photo by Pablo Stanic on Unsplash

Since the 1990s, scientists have debated the underlying cause of Gulf War illness (GWI), a constellation of unexplained and chronic symptoms affecting veterans of the Persian Gulf War. Now researchers have solved the mystery, showing through a detailed genetic study that the nerve gas sarin was largely responsible for the syndrome. The findings were published in Environmental Health Perspectives.

Dr Haley’s research group not only discovered that veterans with exposure to sarin were more likely to develop GWI, but also found that the risk was modulated by a gene that helps break down the nerve gas. Sarin-exposed Gulf War veterans with a weak variant of the gene were more likely to develop symptoms of GWI than other exposed veterans with the strong form of the gene.

“Quite simply, our findings prove that Gulf War illness was caused by sarin, which was released when we bombed Iraqi chemical weapons storage and production facilities,” said Robert Haley, MD, at UT Southwestern, a medical epidemiologist who had led that study and has been investigating GWI for 28 years. “There are still more than 100 000 Gulf War veterans who are not getting help for this illness and our hope is that these findings will accelerate the search for better treatment.”

Multiple causes of Gulf War illness suggested

After the Gulf War, more than a quarter of the US and coalition veterans began reporting a range of chronic symptoms, including fatigue, fever, night sweats, memory and concentration problems, difficulty finding words, diarrhoea, sexual dysfunction, and chronic body pain. Since then, military and academic researchers have studied a list of possible causes of GWI, ranging from stress, vaccinations, and burning oil wells to exposure to pesticides, nerve gas, anti-nerve gas medication, and depleted uranium used in weapons.

“What makes this new study a game-changer is that it links GWI with a very strong gene-environment interaction that cannot be explained away by errors in recalling the environmental exposure or other biases in the data.”

Study leader Robert Haley, MD, medical epidemiologist

Over the years, these studies have identified statistical associations with several of these, but no cause has been widely accepted. Most recently, Dr Haley and a colleague reported a large study testing veterans’ urine for depleted uranium that would still be present if it had caused GWI and found none.

Studies have shown statistical associations with several of these causes, though none received wide acceptance. Dr Haley and a colleague recently reported a large study that found no depleted uranium in veterans’ urine, which would have still been present if it had caused GWI.

“As far back as 1995, when we first defined Gulf War illness, the evidence was pointing toward nerve agent exposure, but it has taken many years to build an irrefutable case,” said Dr Haley.

Sarin’s effects

Sarin is a toxic nerve agent, production of which was banned in 1997. When people are exposed to either the liquid or gas form, sarin enters the body through the skin or breathing and attacks the nervous system. High-level sarin often results in death, but studies on survivors have revealed that lower-level sarin exposure can lead to long-term impairment of brain function. A large release of this gas occurred when a chemical weapons storage plant was bombed, causing thousands of nerve gas alarms to sound.

Previous studies have found an association between Gulf War veterans who self-reported exposure to sarin and GWI symptoms. However, this has raised criticisms of recall bias. “What makes this new study a game-changer is that it links GWI with a very strong gene-environment interaction that cannot be explained away by errors in recalling the environmental exposure or other biases in the data,” Dr Haley said.

In the new paper, Dr Haley and his colleagues studied 508 deployed veterans with GWI and 508 deployed veterans who did not develop any GWI symptoms. They asked whether the veterans had heard chemical nerve gas alarms, indicating sarin exposure, and also collected blood and DNA samples.

The role of PON1

The researchers tested the samples for variants of a gene called PON1, which has two variants. The Q variant generates a blood enzyme that efficiently breaks down sarin while the R variant helps the body break down other chemicals but is not efficient at destroying sarin. Everyone has either a QQ, RR or QR genotype.

For Gulf War veterans with the QQ genotype, hearing nerve agent alarms — a proxy for chemical exposure — raised their chance of developing GWI by 3.75 times, those with the QR genotype had an a 4.43 fold risk increase. And for those with RR genotype, the chance of GWI increased by 8.91 times. Those soldiers with both the RR genotype and low-level sarin exposure were over seven times more likely to get GWI due to the interaction per se, over and above the increase in risk from both risk factors acting alone. For genetic epidemiologists, this number leads to a high degree of confidence that sarin is a causative agent of GWI.

“Your risk is going up step by step depending on your genotype, because those genes are mediating how well your body inactivates sarin,” said Dr Haley. “It doesn’t mean you can’t get Gulf War illness if you have the QQ genotype, because even the highest-level genetic protection can be overwhelmed by higher intensity exposure.”

This kind of strong gene-environment interaction is considered a gold standard for showing that an illness like GWI was caused by a particular environmental toxic exposure, he added. The research doesn’t rule out that other chemical exposures could be responsible for a small number of cases of Gulf War illness. However, Dr. Haley and his team carried out additional genetic analyses on the new data, testing other factors that could be related, and found no other contributing causes.

“There’s no other risk factor coming anywhere close to having this level of causal evidence for Gulf War illness,” said Dr Haley.

The team is continuing research on GWI’s impacts on the body, particularly the immune system, whether any of its effects are reversible, and whether there are biomarkers to detect prior sarin exposure or GWI.

Source: UT Southwestern Medical Center

New Treatment Traps and Kills off Toxoplasma gondii in Host Cells

Toxoplasma gondii, an obligate intracellular human parasite, has a unique cytoskeletal apparatus that is probably used for invading host cells and for parasite replication. Shown here are images of T. gondii constructing daughter scaffolds within the mother cell. Green: YFP-α-Tubulin; bright yellow: mRFP-TgMORN1 (see Hu et al., Figure 6 A-C).
Credit: Image provided by Ke Hu and John M. Murray

A new method blocks the protein regulation of Toxoplasma gondii, causing the parasite to die off inside the host cell, a method which could be adapted to malaria. The approach is detailed in the journal Nature Microbiology.

Toxoplasmosis is one of the most widespread zoonoses worldwide. It is an infectious disease that can be transmitted from cats to humans, and from consumption of raw or undercooked meat. Infection is particularly dangerous for pregnant women, and immunosuppressed HIV/AIDS patients often manifest neurological symptoms.

The cause of the disease is the single-celled parasite T. gondii. Inside the host cell, it forms a parasitophorous vacuole, a tiny compartment facilitating nutrient exchange and synchronised cell division. Up to 64 daughter cells can form inside, connected with each other inside the vacuole via a network. As soon as the offspring are mature, a regulation mechanism prompts the dissolution of the vacuole and the structures that have formed inside it, releasing the daughter cells to invade new host cells.

Hope for the development of new drugs

Previously, it was not known which genes encode the proteins that control the exit from the host cell. To identify them, a team led by Professor Markus Meißner at LMU, collaborated with colleagues from the University of Glasgow in Scotland to develop a novel genetic screening technique based on Cas9 ‘genetic scissors’, and investigate a library of 320 parasite-specific genes. They discovered two genes without which cell egress is impossible.

The targeted destruction of these genes resulted in the exit being trapped and the next generation of parasites dying within the host cell. “This paves the way potentially for the development of active substances that could block the function of the corresponding proteins and so put a halt to propagation,” remarked Prof Markus Meißner.

T. gondii is closely related to the malaria pathogen Plasmodium falciparum. Therefore, the parasite serves as a model organism for the pathogen of the tropical disease, which kills hundreds of thousands of people worldwide every year. “We assume that similar processes control the propagation of the malaria pathogen,” explains LMU parasitologist Dr. Elena Jimenez-Ruiz. “Next, we will investigate what functions these proteins have in the malaria pathogen and whether there are possible starting points for the development of new drugs.”

Source: Ludwig-Maximilians-Universität München

Using Bacteriophage Therapy to Defeat a Resistant Bacterial Infection

A Left upper extremity with multiple large erythematous, fluctuant to nodular lesions ultimately diagnosed as disseminated cutaneous Mycobacterium chelonae infection. B Images of the left upper extremity lesions prior to (Dec 2020) and following (August 2021) addition of bacteriophage therapy. C PET/CT prior to (March 2021) and following (August 2021) addition of bacteriophage therapy. Credit: Nature

Reporting in the journal Nature, clinicians describe the use of a bacteriophage to treat a flesh-eating infection by an antibiotic-resistant bacteria, with excellent clinical response. Bacteriophages, from the Greek ‘bacteria eater’, are viruses which target bacteria.

Bacteriophage (or more simply ‘phage’) therapy is being explored as a solution to the growing threat of antimicrobial resistance. Despite the exotic-sounding name, bacteriophage therapy is nothing new – in fact, its first application in 1919 predates the discovery of penicillin in 1929. However, their use has not been accompanied with robust research, meaning that there is still uncertainty regarding their use in modern medicine.

The authors report treating Mr. M, a 56 year-old man with disseminated cutaneous Mycobacterium chelonae infection with a single bacteriophage in conjunction with antibiotic and surgical management. He had previously received extensive antimicrobial courses as well as surgical debridement, but the bacterial infection persisted.

M. chelonae is a rapidly growing nontuberculous mycobacterium, ubiquitous in the environment and is known to have antimicrobial resistance. In rare cases, it causes infections in immunocompromised patients. To treat the infection, the researchers used a bacteriophage called Muddy, which had been isolated from a South African eggplant.

After the phage therapy skin started, lesions significantly improved both on examination and in PET/CT scans. Furthermore, two biopsies at two and five months post-treatment revealed no evidence of granulomas or AFB on histopathology and tissue cultures have remained negative. The patient has had no adverse events from the phage therapy and administered the intravenous therapy at home for more than six months.

Bacteriophage therapy is hampered by the development of phage resistance, which can potentially be countered using an appropriately-designed phage cocktail. In this case, the researchers were limited to Muddy, since no other phages tested were highly active against the patient’s strain of M. chelonae. Although resistance to Muddy is likely to occur, it was not detected in vitro, consistent with the infrequency of phage resistance in M. abscessus isolates. Resistance in vivo leading to loss of treatment efficacy was also not observed, which together suggest that phage resistance of NTM pathogens may not be the impediment encountered with other pathogens.

A second barrier to the successful treatment of bacterial infections with phage therapy is the complex interaction between the host immune system and the bacteriophage. In this case, the patient maintained stably improved disease and negative microbiologic and histopathologic studies despite a neutralising antibody response to the phage.

The authors suggested that the phage quickly reduced the burden of infection, allowing the ongoing antimicrobial therapy to have an effect. The phage also became self-replicating at the infection site – administration after the onset of neutralising antibodies therefore became unnecessary.

There are still significant challenges to phage therapy becoming widespread. The mains ones are 1) doctors need to know the bacterial strain behind the infection and 2) they need to have several phages on hand that specifically target that strain. Compounding the latter problem, most pharmaceutical companies are hesitant to focus on developing phage therapies. Since phage therapy is over 100 years old, it is difficult to patent and generate revenue to justify the initial development costs.

New Drugs for Cryptococcal Meningitis Sorely Needed in SA

Brain scan image
Image source: Mart Production on Pexels

Despite the greater safety and efficacy of a new short course treatment for HIV-related cryptococcal meningitis (CM), access to the treatment in South Africa will be a challenge, according to a pair of articles by Spotlight.

Following positive results of a trial, the World Health Organization last week announced new recommendations for the treatment of CM, with a single high dose of L-AmB followed by two weeks of flucytosine and fluconazole.

Using L-AmB (AmBisome) and flucytosine for the treatment of CM will be a welcome change for South Africa, which has the world’s highest burden of the condition. This shorter course with fewer side effects than the current treatment involving amphotericin-B could save lives as well as clinical resources in the public sector, but at present the treatment is hamstrung by pricing and availability uncertainty, with a course of L-AmB currently only available at a steep cost.

Amphotericin B [deoxycholate] is a drug that doctors and nurses used to call ampho-terrible,” Amir Shroufi, Médecins Sans Frontières (MSF) Southern Africa board member told Spotlight.

He explained that “it’s a really nasty drug, doctors and nurses don’t like it because it can cause severe anaemia. It’s toxic to the kidneys, so it can cause kidney damage and even kidney failure… and the infusion line used for the drug can often become infected and it can cause inflammation of the veins where it’s going into the body.”

L-AmB is a “much better drug”, he said, with great benefits of administering it for one day as opposed to a week or two. The seriousness of CM meant hospitalisation will still be required, pointed out Dr Jacqui Miot, division director of the Wits Health Economics and Epidemiology Research office, but means that patients won’t be tethered to a drip and may be able to go home sooner.

Under the treatment regimen, a patient receives a single high dose of L-AmB on the first day of treatment, followed by a 14-day course of flucytosine and fluconazole pills.

For a 60kg patient at the recommended dosage, twelve 50mg vials of L-AmB are needed, which at Gilead’s promised access price would be R2 880. Key Oncologics’ currently charges R34 560 for 12 vials.

Even given the availability of L-AmB, Shrouifi warns that “whatever you’re doing, you have to have flucytosine. That’s your baseline, even if you’re giving liposomal amphotericin B, you have to have the flucytosine”.

Flucytosine is an old, off-patent medicine developed in the 1950s. Despite its age and its demonstrated efficacy in the landmark ACTA trial four years ago, flucytosine was only recently authorised for use in South Africa and is only slowly being rolled out.

Amir Shroufi warned that access to the life-saving medicine remains a major issue. “Doctors are not being given the tools they need to treat [CM],” he said. “The first tool they have to have is flucytosine and they still don’t have flucytosine. So, that’s the thing that needs to happen urgently, you know, tomorrow! Everyone with cryptococcal meningitis must get access to flucytosine.”

Like L-AmB, Mylan’s 250mg and 500mg flucytosine tablets were only registered recently, in December 2021. The Department of Health’s target price for a pack of 100 tablets is R1 500. Fortunately, it appears that the Clinton Health Access Initiative (CHAI) will be able to secure packs of 100 at R1 470 each for use in South Africa’s flucytosine access programme.

The next steps for rollout of flucytosine will be inclusion on the national essential medicines list and in CM treatment guidelines before tenders can be put out.

Source 1: Spotlight

Source 2: Spotlight

Obesity in Mice Causes AD Treatments to Backfire

Mouse
Photo by Kanasi on Unsplash

In a new study published in Nature, researchers found that treatments that were effective for atopic dermatitis (AD) in lean mice actually worsened the condition in obese mice.

Tracking the development of AD in obese and lean mice, the researchers found that obese mice developed more inflammation and more severe AD. This increased inflammation was present even after obese mice lost weight. There were similar results in an experimental model of asthma, with obese mice developing more inflammation.

The researchers next looked in detail at immune cells called T cells in lean and obese mice with AD. Lean mice had more TH2 cells, a class of T cells known to play a role in the development of AD. Obese mice had more of a class of T cells called TH17. These cells trigger a different type of inflammation.

Similar trends were seen in blood samples taken from people. Markers of TH17 cell activity increased along with body mass index (BMI) in a database of serum collected from people with AD. Conversely, in samples from patients with severe asthma, TH2 cell activity decreased as BMI increased.

Drugs that block TH2 cell activity are used in the treatment of severe AD as well as asthma and other inflammatory conditions. The researchers tested antibodies to block TH2 cell activity in lean and obese mice with severe AD. While the antibodies reduced skin inflammation in lean mice as expected, they made the condition worse in obese mice. Analysis of immune cells suggested that blocking TH2 cell activity in the obese mice worsened other forms of inflammation.

Obese mice were also found to have less activity of peroxisome proliferator-activated receptor-γ (PPARɣ) in their TH2 cells. When lean mice were engineered to lack PPARɣ, their inflammatory response resembled that of obese mice.

Drugs that increase PPARɣ activity increase insulin sensitivity and are approved for the treatment of type 2 diabetes. The researchers found that giving one of these drugs to obese mice changed their inflammatory response to resemble that of lean mice. It also restored their sensitivity to the antibodies that block TH2 cell activity.

“Our findings demonstrate how differences in our individual metabolic states can have a major impact on inflammation, and how available drugs might be able to improve health outcomes,” said Dr Ronald Evans from the Salk Institute, who helped lead the work.

Source: National Institutes of Health

Gene Mutation in Young Girl May Finally Yield Lupus Treatment

Facial rash characteristic of lupus. Credit: Statpearls

A study published in Nature has identified mutations in an X chromosome gene that senses viral RNA, as a cause of the autoimmune disease lupus, a finding which may explain why the disease is far more common in females, and which might lead to new treatments.

In the study, whole genome sequencing was performed on the DNA of a Spanish child named Gabriela, who was diagnosed with severe lupus at age 7. Such a severe case with early onset of symptoms is rare and suggests a single genetic cause.

In their genetic analysis, the researchers discovered a single point mutation in the TLR7 gene. Referrals from other institutions, they were able to identify other cases of severe lupus where this gene was also mutated.

To confirm that the mutation causes lupus, the team inserted the gene into mice, which went on to develop the disease and showed similar symptoms. The mouse model and the mutation were both named ‘kika’ by Gabriela, the young girl central to this discovery.

Carola Vinuesa, senior author and principal investigator said: “It has been a huge challenge to find effective treatments for lupus, and the immune-suppressors currently being used can have serious side effects and leave patients more susceptible to infection. There has only been a single new treatment approved by the FDA in about the last 60 years.

“This is the first time a TLR7 mutation has been shown to cause lupus, providing clear evidence of one way this disease can arise.”

Professor Nan Shen, co-director of CACPI adds: “While it may only be a small number of people with lupus who have variants in TLR7 itself, we do know that many patients have signs of overactivity in the TLR7 pathway. By confirming a causal link between the gene mutation and the disease, we can start to search for more effective treatments.”

The mutation identified by the researchers makes TLR7 protein bind more readily guanosine and become more active. This in turn increases the sensitivity of the immune cell, making it more likely to incorrectly target healthy tissue.

Interestingly, other studies have shown mutations that cause TLR7 to become less active are associated with some cases of severe COVID infection, highlighting the delicate balance of a healthy immune system.

The findings could also explain why lupus is 10 times more common in females than in males. Because TLR7 is located on the X chromosome, females have two copies of the gene while males have one. Usually, in females one of the X chromosomes is inactive, but in this section of the chromosome, silencing of the second copy is often incomplete. This means females with a mutation in this gene can have two functioning copies.

Study co-author Dr Carmen de Lucas Collantes, said: “Identification of TLR7 as the cause of lupus in this unusually severe case ended a diagnostic odyssey and brings hope for more targeted therapies for Gabriela and other lupus patients likely to benefit from this discovery.”

Gabriela, now a teenager, remains in touch with the research team. She said, “I hope this finding will give hope to people with lupus and make them feel they are not alone in fighting this battle. Hopefully the research can continue and end up in a specific treatment that can benefit so many lupus warriors who suffer from this disease.”

The researchers are now investigating the repurposing of existing treatments which target the TLR7 gene. By targeting this gene, they hope to be able to also help patients with related conditions.

Carola added: “There are other systemic autoimmune diseases, like rheumatoid arthritis and dermatomyositis, which fit within the same broad family as lupus. TLR7 may also play a role in these conditions.”

Source: Francis Crick Institute

Lasting Gains Achieved with Retinal Vein Occlusion Treatment

Eye
Source: Daniil Kuzelev on Unsplash

A treatment for retinal vein occlusion yields long-lasting vision gains, with visual acuity remaining significantly above baseline at five years – though many patients still require ongoing treatment, according to a report published in the American Journal of Ophthalmology. The report marked the five-year outcomes of the Study of Comparative Treatments for Retinal Vein Occlusion 2 (SCORE2).

Retinal vein occlusion (RVO) is caused by a blockage of the veins carrying blood away from the retina, causing macular oedema where fluid becomes trapped within and under the retina, leading to rapid and severe loss of visual acuity. Central retinal vein occlusion (CRVO) is an occlusion of the main retinal vein posterior to the lamina cribrosa of the optic nerve. CRVO has a better prognosis in younger patients. One-third of older patients improve without treatment, one-third stay the same, and one-third get worse.

The leading treatment for RVO is injections of anti-vascular endothelial growth factor (VEGF) drugs, helping to control blood vessel leakage and swelling.

“While anti-VEGF therapy is associated with significant improvement in both retinal swelling and visual acuity in patients with central or hemi-retinal vein occlusion, our findings show that most of the patients followed still required treatment to control the macular oedema for at least five years,” said the chair of the study, Ingrid U. Scott, MD, MPH, at the Penn State College of Medicine. “This demonstrates the importance of continued monitoring of these patients.”

In 2017, SCORE2 clinical trial investigators reported that two types of anti-VEGF treatment were equally effective at improving visual acuity in people with macular oedema due to CRVO or hemi-retinal vein occlusion (HRVO). CRVO affects the entire retina, while HRVO generally affects about half of the retina. Half of the study participants had received bevacizumab while the other half received aflibercept. Participants received monthly injections over six months. At the six-month mark, the vision of participants in both groups had, on average, improved over three lines on an eye chart.

The researchers followed SCORE2 participants for five years, collecting information about their visual acuity, treatments, and whether their macular oedema had resolved. After the initial 12-month study period, participants were treated at their physician’s discretion, most reducing the frequency of anti-VEGF injections and some switching their patients to the other anti-VEGF drug. At five years, many participants had lost some visual acuity compared to the 12-month mark, but they retained on average three lines of improvement compared to baseline.

“It was surprising to us that despite many participants still needing treatment after five years, their visual acuity outcome remained very good,” said Dr Michael Ip, MD, co-chair of the study from the University of California Los Angeles. “In comparison to this treatment for wet age-related macular degeneration, where initial vision improvements fade over time, these results are quite favourable.”

“This five-year study tells us a lot about what’s happening with retinal vein occlusion patients in the real world,” said Dr Scott. “Prior to this study, retinal vein occlusion was widely considered an acute illness. This study shows that RVO is a chronic disease. It also underscores the importance of disease monitoring and individualised treatment to achieve the best possible vision.”

Source: NIH/National Eye Institute

Vigorous Exercise and Talking Produce Similar Levels of Aerosols

Old man jogging
Photo by Barbra Olsen on Pexels

Vigorous exercise produces a similar level of aerosol particles as speaking, but high-intensity exercise produces more, according to new research published in Communications Medicine. This is the first study to measure exhaled aerosols generated during exercise, to help inform the risk of airborne viral transmission of SARS-CoV-2 for gyms and indoor physical training.

Inhalation of infectious aerosol is considered to be the main route of SARS-CoV-2 transmission. In this study, researchers performed a series of experiments to measure the size and concentration of exhaled particles (up to 20µm diameter) which are generated in our respiratory tracts and breathed out, during vigorous and high-intensity exercise.

Using a cardiopulmonary exercise test, 25 healthy participants (13 male, 12 female) with a range of athletic abilities were recruited to undertake four different activities (breathing at rest, speaking at normal conversational volume, vigorous exercise and high-intensity exercise) on a cycle ergometer. Airflow and particles emitted were measured by particle counter. Experiments were carried out in an orthopaedic operating theatre — an environment with ‘zero aerosol background’, letting the researchers to unambiguously identify the aerosols generated by the participants.

The results showed that the size of airborne particles emitted during vigorous exercise was consistent with those emitted while breathing at rest. However, the rate of aerosol mass exhaled during vigorous exercise was found to be similar to speaking at a conversational volume.

Jonathan Reid, scientific lead on the paper, said: “COVID has profoundly impacted sports and exercise, and this study provides a comprehensive analysis of the mass emission rates of aerosol that can potentially carry infectious virus produced from an individual during exercise. Our research has shown that the likely amount of virus that someone can exhale in small aerosol particles when exercising is comparable to when someone speaks at a conversational volume.  The most effective way to reduce risk is to ensure spaces are appropriately ventilated to reduce the risk of airborne transmission.”

Source: University of Bristol

An Oral Drug for Sleep Apnoea

Sleeping man
Photo by Mert Kahveci on Unsplash

A new study published in the American Journal of Respiratory and Critical Care Medicine has tested a sleep apnoea treatment using a drug that inhibits carbonic anhydrase – an enzyme that balances carbonic acid and carbon dioxide in the body. The treatment reduced breathing pauses by more than 20 per hour for patients given the drug.

Several drugs with carbonic anhydrase (CA) inhibitory properties are already available on the market, and used for treatment of glaucoma, epilepsy and other disorders.

Previous research has not systematically tested whether CA inhibitors also might be used to treat obstructive sleep apnoea. A total of 59 patients with moderate or severe sleep apnoea completed the four-week trial, and were randomised to two groups receiving either 400 or 200 mg of the CA inhibitor, and a control group that received placebo.

The results show that, overall, the treatment reduced the number of breathing pauses and promoted oxygenation during the night. A few patients experienced side effects, such as headache and breathlessness, which were more common in those receiving the highest dose.

The study results together with established safety data of the drug sulthiame provide support for continued research on CA inhibition as a new potential treatment for obstructive sleep apnoea.

“Among the patients who received the higher dosage of the drug, the number of breathing pauses decreased by approximately 20 per hour. For just over a third of patients in the study, only half of their breathing pauses were left, and in one in five the number fell by at least 60 percent,” said first authpr Professor Jan Hedner.

The fact that several approved drugs in the CA inhibitor category are available on the market makes fast-tracking development of an approved drug for sleep apnoea practicable. The drug used in this clinical trial was sulthiame, which is sometimes used to treat epilepsy in children.

Current treatment for a patient with sleep apnoea is either an oral appliance therapy or a CPAP (Continuous Positive Airway Pressure) mask. Both help to maintain airway patency during sleep.

“These therapy options take time to get used to and, since they frequently are perceived as intrusive or bulky. Insufficient user time is therefore common. If we develop an effective drug, it will therefore make life easier for many patients and, in the long run, potentially also save more lives,” said senior author Ludger Grote.

Source: University of Gothenburg