Category: Diseases, Syndromes and Conditions

Categories : Diseases, Syndromes and ConditionsTags :

The Emerging Treatment-resistant Fungus Threat

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Professor Rodney E. Rohde, a public health and clinical microbiology expert at Texas State University, warned in article for The Conversation of the growing threat of fungal resistance — a problem drawing much less attention than antibiotic resistance. 

 Athlete’s foot, thrush, ringworm and other ailments are caused by fungi, and some are serious risks to health and life. Among these is Candida auris, a pathogenic fungus. Fungi generally have not caused major disease, so there is a lack of funding in this area and there are limited antifungal agents that can treat C. auris.

Most fungal infections around the world are caused by the genus Candida, particularly the species called Candida albicans. But there are others, including Candida auris, which gets its name ‘auris’, Latin for ear, because it was first identified from an external ear canal discharge in 2009.

Candida normally lives on the skin and inside the body, such as in the mouth, throat, gut and vagina, without causing any problems. It exists as a yeast and is thought of as normal flora, harmless microbes. However when the body is immuno-compromised, these fungi become opportunistic pathogens, something happening around the world with multidrug-resistant C. auris.

The threat of Candida auris

C. auris infections, or fungaemia, have been reported in 30 or more countries. They are often found in the blood, urine, sputum, ear discharge, cerebrospinal fluid and soft tissue, and occur in people of all ages. According to the US Centers for Disease Control, the mortality rate in the US has been reported to be between 30% to 60% in many patients who had other serious illnesses. In a 2018 review of research on the global spread of the fungus, researchers estimated mortality rates of 30% to 70% in C. auris outbreaks among critically ill patients in intensive care.

Recent surgery, diabetes and broad-spectrum antibiotic and antifungal use are risk factors. Furthermore, immuno-compromised patients are at greater risk than those with healthy immune systems.

C. auris can be difficult to identify with conventional microbiological culture techniques, which leads to frequent mis-identification and under recognition. This yeast is also known for its tenacity to easily colonise the human body and environment — including medical devices. People in nursing homes and patients with catheters, on ventilation etc seem to be at highest risk.

The CDC has set C. auris infections at an “urgent” threat level because 90% are resistant to at least one antifungal, 30% to two antifungals, and there are some resistant to all three available classes of antifungals. This multidrug resistance has led to outbreaks in health care settings, especially hospitals and nursing homes, that are extremely difficult to control.

The double threat of COVID and C. auris

For hospitalised COVID patients, antimicrobial-resistant infections may be a particularly devastating risk. The mechanical ventilators often used to treat serious COVID are breeding grounds and highways for entry of environmental microbes like C. auris. Further, according to a September 2020 paper, hospitals in India treating COVID have detected C. auris on surfaces including “bed rails, IV poles, beds, air conditioner ducts, windows and hospital floors.” The researchers termed the fungus a “lurking scourge” amid the COVID pandemic. Termed ‘white fungus’, these fungal infections typically arise a week to 10 days after being in the ICU.

The same authors reported in a November 2020 CDC article that of 596 COVID-confirmed patients in a New Delhi ICU from April 2020 to July 2020, 420 patients required mechanical ventilation. Of these, 15 were infected with candidemia fungal disease and eight of those infected (53%) died. Ten of the 15 patients were infected with C. auris; six of them died (60%).

How to deal with this?

With fewer and fewer antifungal options,  CDC is recommending a focus on preventing C. auris infections. This involves better hand hygiene and improving infection prevention and control in medical care settings, judicious and thoughtful use of antimicrobial medications, and stronger regulation limiting the over-the-counter availability of antibiotics.

Source: The Conversation

Journal information: Anuradha Chowdhary et al, The lurking scourge of multidrug resistant Candida auris in times of COVID-19 pandemic, Journal of Global Antimicrobial Resistance (2020). DOI: 10.1016/j.jgar.2020.06.003

Categories : Diseases, Syndromes and Conditions ImmunologyTags :

In the Immune Battle, MRSA Uses Toxins to Fight Dirty

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Scanning electron micrograph of methicillin-resistant Staphylococcus aureus and a dead human neutrophil. Credit: NIAID

Researchers have uncovered a novel trick employed by the bacterium Staphylococcus aureus — MRSA uses toxins to ‘fight dirty’ and stifle the immune response. This finding is a step towards one day producing a vaccine against MRSA.

Every year, there are some 700 000 deaths due to the emerging global threat of antimicrobial resistance (AMR). Turning the tables against AMR requires immediate action, and the development of novel vaccines to prevent such infections in the first place, are an attractive and potentially very effective option.

Staphylococcus aureus is the causative agent of the infamous MRSA ‘superbug’, one of the chief concerns of AMR. Immunologists from Trinity College Dublin, working with scientists at GSK, discovered the deadly bacteria’s new trick to foil the immune system. They found that the bacterium interferes with the host immune response by causing toxic effects on white blood cells, preventing them from carrying out their infection-fighting jobs.

The study also showed that the toxicity could be lessened following vaccination with a mutated version of a protein specifically engineered to throw a spanner in the MRSA works. This could one day lead to a vaccine for humans.

Rachel McLoughlin, Professor in Immunology in Trinity’s School of Biochemistry and Immunology and the Trinity Biomedical Sciences Institute (TBSI), said: “As a society we are witnessing first-hand the powerful impact that vaccination can have on curbing the spread of infection. However, in the backdrop of the COVID epidemic we must not lose sight of the fact that we are also waging war on a more subtle epidemic of antimicrobial resistant infection, which is potentially equally deadly.

“In this study we have identified a mechanism by which a protein made by the bacterium – known as Staphylococcal Protein A (SpA) – attacks and rapidly kills white blood cells. This protein has been widely studied for its immune evasion capacity and has a well-documented role in rendering antibodies raised against the bacterium non-functional.

“Here we uncover a previously undocumented strategy by which SpA forms immune complexes through its interaction with host antibodies, that in turn exert toxic effects on multiple white blood cell types. This discovery highlights how important it will be for effective vaccines to be capable of disarming the effects of protein A.”

Dr Fabio Bagnoli, Director, Research & Development Project Leader, GSK, said: “Our collaboration with Trinity College Dublin and in particular with Professor Rachel McLoughlin, a worldwide recognised expert on staphylococcal immunology, is critical for increasing our knowledge on protective mechanisms against S. aureus.”

The study documents the latest discovery made by this group at Trinity under an ongoing research agreement with GSK Vaccines (Siena, Italy). Overall, this collaboration aims to increase understanding of the immunology of Staphylococcus aureus infection to advance development of next-generation vaccines to prevent MRSA infections.

Source: Trinity College Dublin

Journal information: Fox, P. G., et al. (2021) Staphylococcal Protein A Induces Leukocyte Necrosis by Complexing with Human Immunoglobulins. Scientific Reports. doi.org/10.1128/mBio.00899-21.

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Double Threat of Flu and S. Pneumoniae Unravelled

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Streptococcus pneumoniae bacteria. Image by CDC on Unsplash

Researchers have found a further reason for why flu and Streptococcus pneumonia are such a deadly combination, by a surface protein causing it to stick to dead or dying lung cells. The finding by University of Alabama at Birmingham (UAB) follows thirty years after the discovery of the surface protein, called pneumococcal surface protein A, or PspA.

This new mechanism had been overlooked because it facilitates bacterial adherence only to dead or dying lung epithelial cells, not to living cells. Previously, researchers typically used healthy lung cell monolayers to search for bacterial adhesins that aid infection. In flu, the virus killing off lung cells was found to set the stage for S. pneumonia attachment to the airway, thereby worsening disease and pneumonia.

Study leaders Carlos Orihuela, PhD, and David Briles, PhD, professor at UAB, said their findings provide further explanation for how an infection by influenza A flu virus — followed by S. pneumoniae superinfection — causes severe pneumonia and a high death rate. Understanding of this mechanism could also lead to improvements for disease treatment and vaccination.

A historical example of the deadly synergy of flu infection followed by S. pneumoniae superinfection is found in banked lung samples from the 1918 Spanish influenza pandemic that killed 40 million to 50 million people — the vast majority of these samples showed co-infection or secondary infection with S. pneumonia.

The UAB research on PspA began with puzzling results from experimental lung infections of mice with influenza A, followed by either wild-type S. pneumonia that has the intact PspA gene, or a mutant S. pneumoniae that lacks PspA. Lung homogenates from mice infected with the wild-type had much higher numbers of S. pneumonia bacteria than lungs infected with the mutant. However, when researchers washed the interiors of the lungs and collected that bronchoalveolar lavage fluid, they counted similar numbers of the wild-type S. pneumonia and the mutant.

“This unexpected result was interpreted to mean that wild-type S. pneumoniae were more resistant to dislodgement than S. pneumonia with a pspA gene deletion, and it served as rationale for further experimentation,” Dr Orihuela said.

From this, the researchers were then able to show that PspA functions as an adhesin to dying host cells, as well as its previously established virulence mechanisms. The researchers also detailed the molecular mechanism of this bacterial adherence.

Both influenza A infection and release of the S. pneumoniae toxin pneumolysin cause death of lung epithelial cells. As they are dying, cells’ phosphatidylserine residues wind up on the outer cell membrane, where they bind the host enzyme glyceraldehyde-3-phosphate dehydrogenase, or GAPDH. In turn, the S. pneumoniae PspA on the bacteria surface binds to the GAPDH. PspA-GAPDH-mediated binding to lung cells increased S. pneumoniae localisation in the lower airway, and this was enhanced by pneumolysin exposure or co-infection with influenza A virus.

One of the fragments of protein responsible for the binding was introduced into the lungs of influenza-infected mice and reduced the disease severity of S. pneumoniae superinfection, presumably through binding competition.

“Our findings support the targeting of regions of PspA for therapeutic and vaccine development against influenza A/Streptococcus pneumoniae superinfections,” Dr Orihuela said. “Importantly, and despite more than 30 years since its discovery, PspA was not previously shown to function as an adhesin. Thus, our finding of PspA’s role in adherence substantially advances our knowledge on the interactions of S. pneumoniae with its host.”

Source: University of Alabama at Birmingham

Journal information: Sang-Sang Park et al, Streptococcus pneumoniae binds to host GAPDH on dying lung epithelial cells worsening secondary infection following influenza, Cell Reports (2021). DOI: 10.1016/j.celrep.2021.109267

Categories : Diseases, Syndromes and Conditions HIV UncategorizedTags :

High Burden of Uncontrolled Disease in KwaZulu-Natal

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Photo by Hush Naidoo on Unsplash

A comprehensive health-screening program has found a high burden of poorly controlled or uncontrolled disease KwaZulu-Natal, along with a high incidence of undiagnosed diseases.

The study, published in The Lancet Global Health, found that four out of five women over 30 had a chronic health condition, and that the HIV-negative population and older people had the highest burden of undiagnosed or poorly controlled non-communicable diseases such as diabetes and hypertension. The study was conducted at the Africa Health Research Institute (AHRI).

Study co-leader Emily Wong, MD, at AHRI in Durban, said: “The data will give AHRI researchers and the Department of Health critical indicators for where the most urgent interventions are needed,” Dr Wong said. “The research was done before COVID, but it has highlighted the urgency of diagnosing and treating people with non-communicable diseases — given that people with uncontrolled diabetes and hypertension are at higher risk of getting very ill with COVID.” 

HIV-associated tuberculosis infections are particularly prevalent in Durban. Dr Wong of the University of Alabama works there to understand the impact of HIV infection on tuberculosis pathogenesis, immunity and epidemiology. In sub-Saharan Africa, 15 years of intense public health efforts that increased access to antiretroviral therapy has resulted in decreased AIDS mortality and raised life expectancy. As a result, there is an increasing priority to address other causes of disease, including tuberculosis and non-communicable diseases.

Over 18 months, health workers screened 17 118 people aged 15 years and older via mobile camps within 1 kilometre of each participant’s home in the uMkhanyakude district. They found high and overlapping burdens of HIV, tuberculosis, diabetes and hypertension among men and women.

While the HIV cases were largely well diagnosed and treated, some demographic groups  still had high rates of undiagnosed and untreated HIV, such as men in their 20s and 30s. In contrast, the majority of people with tuberculosis, diabetes or hypertension were either undiagnosed or not well controlled. Of particular concern was the high rates of undiagnosed and asymptomatic tuberculosis discovered, as it remains one of the leading causes of death in South Africa.

“Our findings suggest that the massive efforts of the past 15 years to test and treat for HIV have done very well for that one disease,” Dr Wong said. “But in that process, we may have neglected some of the other important diseases that are highly prevalent.”

The mobile camps screened for diabetes, high blood pressure, nutritional status (obesity and malnutrition), and tobacco and alcohol use, as well as HIV and tuberculosis. The tuberculosis screening component included high-quality digital chest X-rays and sputum tests for people who reported symptoms or had abnormal X-rays. Clinical information was combined with 20 years of population data from AHRI’s health and demographic surveillance research. Using a sophisticated data system combined with artificial intelligence to interpret the chest X-rays, AHRI’s clinical team examined the information in real time, referring people to the public health system as needed.

The study found that: 

  • Half of the participants had at least one active disease, and 12 percent had two or more diseases. Diabetes and hypertension incidences were 8.5 percent and 23 percent, respectively.
  • One-third of the people were living with HIV, but this was mostly well diagnosed and treated. A particularly high burden of HIV, high blood pressure and diabetes was seen in women.
  • For tuberculosis, 1.4 percent of the people had active disease, and 22 percent had lifetime disease. About 80 percent of the undiagnosed tuberculosis was asymptomatic, with higher rates of active tuberculosis seen in men.
  • Several disease patterns varied by geographical location — eg, the highest HIV burden was seen near main roads, while higher rates of tuberculosis and non-communicable diseases were seen in more remote areas.

Source: University of Alabama at Birmingham

Journal information: Wong, E. B., et al. (2021) Convergence of infectious and non-communicable disease epidemics in rural South Africa: a cross-sectional, population-based multimorbidity study. The Lancet Global Health. doi.org/10.1016/S2214-109X(21)00176-5.

Categories : Diseases, Syndromes and Conditions General InterestTags :

Study Reveals Mediaeval Plague Victims Buried With Care and Attention

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Photo by Peter Kvetny on Unsplash

Mediaeval plague victims in the UK were mostly buried with care and attention, according to a new study from Cambridge University. 

In the mid-14th century, Europe was devastated by the Black Death which killed between 40 and 60 per cent of the population. For centuries afterward, waves of plague would continue to strike the region.

Due to the rapid onset of death in the absence of antibiotic treatment (less than a week for bubonic plague and under 48h for pneumonic plague), the disease leaves no visible evidence on the skeleton, so until now archaeologists have been unable to identify individuals who died of plague unless they were buried in mass graves.

Although it has been long believed that most plague victims in fact received an individual burial, this has been impossible to confirm until now.

By studying DNA extracted from the teeth of individuals who died at this time, researchers from the Wellcome Trust-funded After the Plague project, based at the Department of Archaeology, University of Cambridge, have identified the presence of Yersinia Pestis, the bacterial pathogen that causes plague. The study is available to read online in the European Journal of Archaeology.

These include people who received normal individual burials at a parish cemetery and friary in Cambridge and in the nearby village of Clopton.

Lead author Craig Cessford of the University of Cambridge explained: “These individual burials show that even during plague outbreaks individual people were being buried with considerable care and attention. This is shown particularly at the friary where at least three such individuals were buried within the chapter house. The Cambridge Archaeological Unit conducted excavations on this site on behalf of the University in 2016-2017.”

The individual at the parish of All Saints by the Castle in Cambridge was also buried with care; this stand in contrast to the apocalyptic language used to describe the abandonment of this church in 1365 when it was reported that the church was partly in ruins and ‘the bones of dead bodies are exposed to beasts’.”

The study also shows that some plague victims in Cambridge did, as expected, receive mass burials.

Yersinia Pestis was also identified in several parishioners from St Bene’t’s, who were found buried together in a large trench in the churchyard excavated by the Cambridge Archaeological Unit on behalf of Corpus Christi College.

Soon afterwards, this part of the churchyard was transferred to Corpus Christi College, which was founded by the St Bene’t’s parish guild to commemorate the dead including the victims of the Black Death. For centuries, the members of the College would walk over the mass burial every day on the way to the parish church.

Cessford concluded, “Our work demonstrates that it is now possible to identify individuals who died from plague and received individual burials. This greatly improves our understanding of the plague and shows that even in incredibly traumatic times during past pandemics people tried very hard to bury the deceased with as much care as possible.”

Source: University of Cambridge

Journal information: “Beyond Plague Pits: Using Genetics to Identify Responses to Plague in Medieval Cambridgeshire” – Craig Cessford, Christiana L. Scheib, Meriam Guellil, Marcel Keller, Craig Alexander, Sarah A. Inskip and John E. Robb. European Journal of Archaeology, https://doi.org/10.1017/eaa.2021.19

Categories : COVID Diseases, Syndromes and ConditionsTags :

A Common Cold Virus Could Stifle COVID

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Photo by Kelly Sikkema on Unsplash

There might be an unexpected benefit to the rhinovirus, or the most frequent cause of the common cold — protection against COVID, according to a study at Yale University.

Around 200 viruses cause the common cold, of which rhinovirus is the most common. Researchers found that the rhinovirus kick-starts interferon-stimulated gene activity. Within airway tissues infected with the rhinovirus, this also can halt replication of the SARS-CoV-2 virus.

Setting off these defences early in the course of COVID infection might prevent or treat the infection, said Ellen Foxman, assistant professor of laboratory medicine and immunobiology at the Yale School of Medicine and senior author of the study. One method is treating patients with interferons, an immune system protein which is also available as a drug.

“But it all depends upon the timing,” Prof Foxman clarified.

In later stages of COVID, high interferon levels correlate with worse disease and may fuel overactive immune responses, according to previous research. But recent genetic studies show that interferon-stimulated genes may actually also be protective in cases of COVID infection.

Prof Foxman’s lab wanted to study this defence system early in the course of COVID infection.

Earlier studies by the lab had shown that common cold viruses may protect against influenza, so they decided to find out whether rhinoviruses would have the same beneficial impact against the COVID virus. The researchers infected lab-grown human airway tissue with SARS-CoV-2 and found that for the first three days, viral load in the tissue doubled about every six hours. However, replication of the coronavirus was completely halted in tissue which had been exposed to rhinovirus. When antiviral defences were blocked, the SARS-CoV-2 could replicate in airway tissue previously exposed to rhinovirus.

The same defences slowed down SARS-CoV-2 infection even without rhinovirus, but only with a low infectious dose, suggesting that the viral load at the time of exposure affects whether the body can effectively fight the infection.

The researchers also studied nasal swab samples from patients diagnosed close to the start of infection. They found evidence of rapid growth of SARS-CoV-2 in the first few days of infection, followed by activation of the body’s defenses. According to their findings, the virus typically increased rapidly for the first few days of infection, before host defenses kicked in, doubling about every six hours; in some patients the virus grew even faster.

“There appears to be a viral sweet spot at the beginning of COVID, during which the virus replicates exponentially before it triggers a strong defence response,” Foxman said.

Interferon treatment is promising but could be tricky, she said, because it would be mostly effective in the days immediately after infection, when many people are asymptomatic. In theory, interferon treatment could be used prophylactically in people at high risk who have been in close contact with others diagnosed with COVID. Interferon is being trialled in COVID, and there appears to be a benefit when given early, but not late.

The study helps explain why influenza infections are lowered at times of the year when the common cold is prevalent, Prof Foxman said. The easing of social distancing measures could cause the common cold and flu viruses, which have been suppressed, to spring back with greater force. Respiratory viruses interference with each other could be a mitigating factor, creating an ‘upper limit’ on the degree to which respiratory viruses circulate together, she said.

“There are hidden interactions between viruses that we don’t quite understand, and these findings are a piece of the puzzle we are just now looking at,” Prof Foxman said.

Source: Yale University

Journal information: Cheemarla, N.R., et al. (2021) Dynamic innate immune response determines susceptibility to SARS-CoV-2 infection and early replication kinetics. Journal of Experimental Medicine.doi.org/10.1084/jem.20210583.

Categories : COVID Diseases, Syndromes and ConditionsTags :

Normal Breathing Can Transport Viruses Over 2 Metres

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Researchers have demonstrated that normal breathing can transport viruses in saliva droplets up a distance of up to 2.2 metres in 90 seconds.

The World Health Organization and the Centers for Disease Control recommend social distancing to prevent the spread of COVID. The distances are estimated from various studies, but there is a need for further research into how viruses are transported from one person to another. 
Previous studies considered aerosol transport after coughing or sneezing, while this study focused on normal human breathing, using computer simulations with a more realistic model than prior studies. A normal breath produces periodic jet flows that contain saliva droplets, but those jets’ velocity is less than a tenth that of a cough or sneeze.

Wearing a face mask greatly reduces the distance which these droplets can travel. Saliva droplets restricted by a mask had travelled only 0.72 metres after two minutes, far short of the distance of 1.8 metres suggested by the CDC.

The investigators found even normal breathing produces a complex field of vortices that can move saliva droplets away from the person’s mouth. The role of these vortices has not previously been understood.

Study author, Ali Khosronejad, American Institute of Physics said: “Our results show that normal breathing without a facial mask generates periodic trailing jets and leading circular vortex rings that propagate forward and interact with the vortical flow structures produced in prior breathing cycles.”

This complex vorticity field can enable the transport of aerosol droplets over long distances despite the slow speeds. A face mask serves to dissipate the kinetic energy of the jet produced by an exhaled breath, thereby disrupting the vortices and limiting the travel of virus-laden droplets.

The researchers also took into account evaporation of the saliva droplets. With no mask, they found the saliva droplets near the front of the plume of exhaled breath had partially evaporated, reaching a size of only one-tenth of a micrometre. In stagnant indoor air, it would take days for droplets this small to settle to the ground.

Masks partially redirect the exhaled breath downward, significantly restricting forward motion of the plume, so the risk of suspended droplets remaining in the air is substantially reduced.

“To simplify the breathing process, we did not consider the flow of air-saliva mixture through the nose and solely accounted for the flow through the mouth,” Khosronejad said. “In future studies, we will explore the effect of normal breathing via both the nose and mouth.”

Source: News-Medical.Net

Journal reference: Khosronejad, A., et al. (2021) A computational study of expiratory particle transport and vortex dynamics during breathing with and without face masks. Physics of Fluids. doi.org/10.1063/5.0054204.

Categories : COVID Diseases, Syndromes and ConditionsTags :

Why the Origin of COVID Matters

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Photo by Artem Podrez from Pexels

As interest mounts in the ‘lab leak’ hypothesis for the origin of SARS-CoV-2, more scientists are starting to take it seriously, especially because of the important implications of its actual origins.

MedPage Today reported that many experts it approached for the story were hesitant to speculate on its exact implications, they agreed that further research into its origins is important to ward off future pandemics.

A natural origin’s implications

Back in 2007, scientists who were studying coronaviruses warned: “The presence of a large reservoir of SARS-CoV–like viruses in horseshoe bats… is a time bomb. The possibility of the re-emergence of SARS and other novel viruses… should not be ignored.”

On May 26 2021, in the midst of the greatest disaster the world has faced since World War II, US President Joe Biden gave US intelligence 90 days to reach a “definitive conclusion” on the origins of SARS-CoV-2.

Vincent Racaniello, PhD, professor of microbiology and immunology at Columbia University, said finding an answer is unlikely within Biden’s deadline. After all, it took 14 years to find the ancestor of the first SARS virus in wildlife.

For Prof Racaniello, this renewed concern underscores the need for better surveillance of viruses in wildlife.

“All human viruses begin in nature. There’s an overwhelming preponderance of data that shows that, so it makes sense to look in nature when we’re looking for the source of new viruses,” Prof Racaniello told MedPage Today.

As a result of human population pressure, more viruses are spilling over into humans from nature. Examples of this include Ebola, SARS-1, MERS, and bird and swine flu. Because of the evolutionary closeness of mammals and humans, they are major pathogen sources. Rodents and bats (accounting for 20% of mammals), as well as various species of birds are good places to look. However our surveillance of wildlife is spotty, so we have “very little” understanding of the viruses these types of animals harbour, and which ones could be threats to humans, Prof Racaniello warned.

“We need to do more wildlife sampling, to find out what’s out there and what’s potentially a threat,” he said. “More investment in this could have prevented the trillions of dollars that we’ve spent to take care of this pandemic.”

A lab leak’s implications

On the other hand, Richard Ebright, PhD, a molecular biologist and professor of chemistry and chemical biology at Rutgers University in New Jersey, believes the real issue lies in addressing the potential for future pandemics that could originate from lab accidents, a discussion that “needs to begin now.”

“Irrespective of whether COVID originated in a natural accident or a lab accident, the risk of a future pandemic originating in a lab accident is real,” he told MedPage Today.

Prof Ebright explained that, in the US and other countries, only voluntary biosafety guidelines exist, and these are about preventing accidental release of pathogens. While the US has legal regulations against several pathogens that could be used as biological weapons, there are no biosecurity regulations for other pathogens. In most of the world, no biosecurity regulations exist for pathogens other than smallpox, not even voluntary ones, Prof Ebright said.

In 2017, the US implemented a bio-risk policy requiring a risk-benefit analysis before federal funding can be approved for high-risk research, such as ‘gain of function’ research that could be used to increase a pathogen’s transmissibility or pathogenicity to better understand and control it, Prof Ebright said. But this bio-risk policy has been essentially ignored by federal agencies, and the other countries with bio-risk policies only apply it to smallpox.

“Discussion now, especially among policy makers and the public, needs to turn to the inadequacy of biosafety, biosecurity, and biorisk-assessment standards worldwide, and to the essentially complete absence of biosafety regulation worldwide,” he said.

The return of the lab leak hypothesis

While evidence is largely circumstantial, the basic idea is that a laboratory at the Wuhan Institute of Virology had been experimenting on a virus called RaTG13 (a coronavirus closely related to SARS-CoV-2, which infects horseshoe bats), and genetically manipulating other horseshoe bat viruses collected around China. It is thought that one of these laboratory viruses could have infected a staffer at the institute, who then transmitted it to the broader public, Dr Ebright explained.

Following the WHO’s March 30 SARS-CoV-2 origins investigation report, there was a sudden about-face and the lab leak theory began to be taken seriously. Though investigators classified a laboratory origin as “extremely unlikely”, they said the conclusion was reached on the evidence made available.

Even the Director-General of the WHO, Dr Tedros Ghebreyesus, said at the time that he did not believe the assessment of a laboratory origin was “extensive enough,” that this hypothesis “requires further investigation,” and that “this report is a very important beginning, but it is not the end.”

“At this point in time, all scientific data related to the genome sequence of SARS-CoV-2 and the epidemiology of COVID are equally consistent with a natural-accident origin or a laboratory-accident origin,” Ebright said.

While the WHO report does not propose a follow-up study for laboratory origins, it acknowledges that both “follow-up of new evidence” and “regular administrative and internal review of high-level biosafety laboratories worldwide” is needed.

Source: MedPage Today

Categories : Diseases, Syndromes and ConditionsTags :

UTI Bacteria Traced to Meat Production

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A Portuguese study has found that bacteria in urinary tract infections (UTI) can be traced back to meat through the production chain where it was prepared.

UTIs are caused by both Gram-negative and Gram-positive bacteria, as well as by certain fungi. Staphylococcus saprophyticus is a major cause of UTI in young women, reaching 20% prevalence. Understanding the epidemiology of this microorganism can help identify its origin, distribution, causes, and risk factors. Researchers from ITQB NOVA led by Maria Miragaia showed that Staphylococcus saprophyticus can originate in food, specifically in the meat-production chain. Their findings were published in the journal Emerging Infectious Diseases.

Pork is the most popular meat type in Europe. S. saprophyticus can be a contaminant of that meat, and it is also found in the environment, the gut and rectal flora of pigs, and in the human gastrointestinal tract, vagina, and perineum.

The researchers used a combination of phenotypic, genomic, and pan-genome wide association approaches, which enabled them to identify two different lineages (G and S) of S. saprophyticus. Lineage G is of food origin and transmitted to humans by contact with food products, and lineage S is of human origin. Both cause disease and may be transmitted directly or indirectly between persons within the community, with an extensive geographic distribution possible.

To find out if these bacteria causing UTIs could be related to the ones found in pork, the research group looked at S. saprophyticus from a slaughterhouse and compared them to those causing human UTIs. The team analysed bacteria collected from UTIs worldwide over two decades, and from UTIs and pork meat production chain in Portugal.

The results showed that bacteria found in the slaughterhouse (equipment, meat, colonisation of workers) were similar to human UTI bacteria and had the same antibiotic resistance profile.

Although S. saprophyticus colonisation rate in pigs was extremely low (1%), 35% of slaughterhouse samples were contaminated. The presence of an antiseptic resistance gene (qacA) by all the lineage G bacteria could be part of the explanation for the ineffective cleaning procedures that were used. 
“S. saprophyticus strains of animal origin (lineage G) enters the slaughterhouse through food animals, persist on the equipment, disseminate and contaminate the meat processing chain and humans. Human colonisation is a crucial step for the later occurrence of UTI,” explained first author Opeyemi Lawal.

The researchers also studied genomic data of bacteria collected from patients attending three hospitals in the Lisbon area, and found that the transmission of these pathogenic bacteria from both lineages (G and S) occurs between persons within the community. Making use of this deep-structured analysis, researchers were also able to identify putative new virulence factors for this unexplored bacterium. The team will continue to search for reservoirs of this bacterium in humans and animals, and to study the mechanisms of S. saprophyticus dissemination and disease to inform strategies against  this pathogen. 

“This a clear example of how food manipulation can impact in human health, and how important it is to educate consumers regarding good individual hygiene practices to avoid spreading of infectious diseases“, said Maria Miragaia, head of the Bacterial Evolution and Molecular Epidemiology Lab. 

“This adds to the list of bacteria that are transmitted to humans through contact with animals and animal-derived food. But the exact mechanisms associated to the conversion from a coloniser to an infectious agent remains to be clarified”, added Henrik Westh from the Copenhagen University Hospital – Amager and Hvidovre, University of Copenhagen (Denmark).

Source: ITQB NOVA

Categories : Diseases, Syndromes and ConditionsTags :

First Detection of Zika Viral DNA in African Bats

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Image source: Ekamalev at Unsplash

Researchers have, for the first time, detected Zika virus RNA in free-ranging African bats, which indicates that the bats were previously infected with Zika virus at the time the samples were taken. 

This discovery also marks the first time scientists have published a study on the detection of Zika virus RNA in any free-ranging bat.

The findings have ecological implications and raise questions about how bats are exposed to Zika virus in the wild. The study was led by Dr Anna Fagre, a veterinary postdoctoral fellow at Colorado State University’s Center for Vector-Borne Infectious Diseases. The findings were detailed in the journal Scientific Reports.

Dr Fagre said that while other studies have shown that bats are susceptible to Zika virus in controlled experimental settings, detection of nucleic acid in bats in the wild indicates that it was transmitted by bites from infected mosquitoes.

“This provides more information about the ecology of flaviviruses and suggests that there is still a lot left to learn surrounding the host range of flaviviruses, like Zika virus,” she said. Other flaviviruses that cause disease in humans include West Nile and dengue.

Wide-ranging samples

Senior author Rebekah Kading, Assistant Professor at CSU, said she, Dr Fagre and the research team were hoping the project would help them to find out more about potential reservoirs of Zika virus.

With 198 samples from bats gathered in the Zika Forest and surrounding areas in Uganda, the team confirmed Zika virus in four bats representing three species. The samples date back as far as 2009 from different parts of Uganda, which is years before the large Zika outbreaks in 2015 to 2017 in North and South America.

The Zika virus was declared a public health emergency by the World Health Organization in February 2016 owing to its association with the congenital deformities, particularly microcephaly in infants borne to the infected mothers

“We knew that flaviviruses were circulating in bats, and we had serological evidence for that,” said Prof Kading. “We wondered: Were bats exposed to the virus or could they have some involvement in transmission of Zika virus?”

The virus detected by the team in the bats was most closely related to the Asian lineage Zika virus, the strain that caused the epidemic in the Americas following outbreaks in Micronesia and French Polynesia. The Asian lineage Zika virus was in late 2016 first detected in Africa, in Angola and Cape Verde.

“Our positive samples, which are most closely related to the Asian lineage Zika virus, came from bats sampled from 2009 to 2013,” said Prof Fagre. “This could mean that the Asian lineage strain of the virus has been present on the African continent longer than we originally thought, or it could mean that there was a fair amount of viral evolution and genomic changes that occurred in African lineage Zika virus that we were not previously aware of.”

Likely incidental hosts, not reservoirs

Prof Fagre said that the relatively low prevalence of Zika virus found indicates that bats may only be incidental hosts of Zika virus infection, rather than amplifying hosts or reservoir hosts.

“Given that these results are from a single cross-sectional study, it would be risky and premature to draw any conclusions about the ecology and epidemiology of this pathogen, based on our study,” she said. “Studies like this only tell one part of the story.”

The research team also made an assay for the study which focuses on subgenomic flavivirus RNA, sfRNA, which flaviviruses possess. Testing for Zika normally uses PCR, polymerase chain reaction, to identify bits of genomic RNA, the nucleic acid that results in the production of protein, said Fagre.

The team’s next steps will be to characterise how long these RNA fragments persist in tissues, which will allow them to estimate how long ago these bats were infected with Zika virus, Prof Kadling said.

“There is always a concern about zoonotic viruses,” she said. “The potential for another outbreak is there and it could go quiet for a while. We know that in the Zika forest, where the virus was first found, the virus is in non-human primates. There are still some questions with that as well. I don’t think Zika virus has gone away forever.”

Source: Colorado State University

Journal information: Fagre, A. C., et al. (2021) Subgenomic flavivirus RNA (sfRNA) associated with Asian lineage Zika virus identified in three species of Ugandan bats (family Pteropodidae). Scientific Reports. doi.org/10.1038/s41598-021-87816-5.