Carbohydrates may be key to better malaria vaccine: study

Agencies
September 17, 2017

Melbourne, Sept 17: Scientists have for the first time found that carbohydrates on the surface of malaria parasites play a critical role in malaria's ability to infect mosquito and human hosts.

The discovery may help improve the only vaccine approved to protect people against Plasmodium falciparum malaria - the most deadly form of the disease, researchers said.

The study found that the malaria parasite 'tags' its proteins with carbohydrates in order to stabilise and transport them, and this process was crucial to completing the parasite's lifecycle.

"We found that the parasite's ability to 'tag' key proteins with carbohydrates is important for two stages of the malaria lifecycle," said Justin Boddey, from Walter and Eliza Hall Institute in Australia.

"It is critical for the the earliest stages of human infection, when the parasite migrates through the body and invades in the liver, and later when it is transmitted back to the mosquito from an infected human, enabling the parasite to be spread between people," said Boddey, who led the study published in the journal Nature Communications.

Interfering with the parasite's ability to attach these carbohydrates to its proteins hinders liver infection and transmission to the mosquito, and weakens the parasite to the point that it cannot survive in the host, researchers said.

Malaria infects over 200 million people worldwide each year and kills around 650,000 people, predominantly pregnant women and children.

Efforts to eradicate malaria require the development of new therapeutics, particularly an effective malaria vaccine.

The first malaria vaccine approved for human use - RTS,S/AS01 - was approved by European regulators in July 2015 but has not been as successful as hoped, with marginal efficacy that wanes over time, researchers said.

"The protein used in the RTS,S vaccine mimics one of the proteins we have been studying on the surface of the malaria parasite that is readily recognised by the immune system," said Ethan Goddard-Borger from Walter and Eliza Hall Institute.

"With this study, we have shown that the parasite protein is tagged with carbohydrates, making it slightly different to the vaccine, so the antibodies produced may not be optimal for recognising target parasites," Goddard-Borger said.

He said there were many documented cases where attaching carbohydrates to a protein improved its efficacy as a vaccine.

"It may be that a version of RTS,S with added carbohydrates will perform better than the current vaccine," Goddard-Borger said.

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Agencies
July 14,2020

UN, Jul 14: There will be no return to the "old normal" for the foreseeable future as a result of the ongoing COVID-19 pandemic, and too many countries were still headed in the wrong direction, the chief of the World Health Organization (WHO) warned.

"The virus remains public enemy number one, but the actions of many governments and people do not reflect this," Xinhua news agency quoted WHO Director-General Tedros Adhanom Ghebreyesus at as saying a regular briefing on Monday.

He noted that mixed messages from leaders are undermining trust, which is the most critical ingredient of any response, while the only aim of the virus is to find people to infect.

Things are going to "get worse and worse and worse", he warned, unless governments communicate clearly with their citizens and roll out a comprehensive strategy focused on suppressing transmission and saving lives, while populations follow the basic public health principles of physical distancing, hand washing, wearing masks, coughing etiquette and staying home when sick.

COVID-19 has been gaining its momentum lately.

According to Tedros, Sunday saw a record of 230,000 cases reported to WHO, of which almost 80% were from just 10 countries and about half from just two countries.

"But it does not have to be this way," he said, asking every single leader, government and individual "to do their bit to break the chains of COVID-19 transmission and end the collective suffering".

To control the disease and get on with people's lives, Tedros said, three things are required. The first is to focus on reducing mortality and suppressing transmission; the second is to focus on an empowered, engaged community that takes individual behaviour measures in the interest of each other.

And the third is a strong government leadership and coordination of comprehensive strategies that are communicated clearly and consistently.

"We weren't prepared collectively, but we must use all the tools we have to bring this pandemic under control. And we need to do it right now," he added.

At the WHO briefing on Monday, health experts also said there was evidence to suggest that children under the age of 10 were only very mildly affected by Covid-19, while those over 10 seemed to suffer similar mild symptoms to young adults.

To what extent children can transmit the virus, while it appears to be low, remains unknown.

On Tuesday, the number of global coronavirus cases cross the 13 million mark, according to the Johns Hopkins University.

The total number of cases currently stood at 13,070,097, while the fatalities rose to 572,411, the University's Center for Systems Science and Engineering (CSSE) revealed in its latest update.

The US accounted for the world's highest number of infections and fatalities at 3,363,056 and 135,605, respectively, according to the CSSE.

Brazil came in the second place with 1,884,967 infections and 72,833 deaths.

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Agencies
May 14,2020

COVID-19 mostly kills through an overreaction of the immune system, whose function is precisely to fight infections, say scientists who have decoded the mechanisms, symptoms, and diagnosis of the disease caused by the SARS-Cov-2 coronavirus.

In a study published in the journal Frontiers in Public Health, the researchers explained step-by-step how the virus infects the airways, multiplies inside cells, and in severe cases causes the immune defences to overshoot with a "cytokine storm".

This storm is an over-activation of white blood cells, which release too-great amounts of cytokines -- inflammation-stimulating molecules --into the blood, they said.

"Similar to what happens after infection with SARS and MERS, data show that patients with severe COVID-19 may have a cytokine storm syndrome," said study author Daishun Liu, Professor at Zunyi Medical University in China.

"The rapidly increased cytokines attract an excess of immune cells such as lymphocytes and neutrophils, resulting in an infiltration of these cells into lung tissue and thus cause lung injury," Liu said.

The researchers explained that the cytokine storm ultimately causes high fever, excessive leakiness of blood vessels, and blood clotting inside the body.

It also causes extremely low blood pressure, lack of oxygen and excess acidity of the blood, and build-up of fluids in the lungs, they said.

The researchers noted that white blood cells are misdirected to attack and inflame even healthy tissue, leading to failure of the lungs, heart, liver, intestines, kidneys, and genitals.

This multiple organ dysfunction syndrome (MODS) may worsen and shutdown the lungs, a condition called acute respiratory distress syndrome, (ARDS), they said.

This, the researchers explained, happens due to the formation of a so-called hyaline membrane -- composed of debris of proteins and dead cells -- lining the lungs, which makes absorption of oxygen difficult.

Most deaths due to COVID-19 are therefore due to respiratory failure, they said.

The researchers explained that in the absence of a specific antiviral cure for COVID-19, the goal of treatment must be to the fight the symptoms, and lowering the mortality rate through intensive maintenance of organ function.

For example, an artificial liver blood purification system or renal replacement therapy can be used to filter the blood through mechanical means, they said.

The team noted that especially important are methods to supplement or replace lung function, for example with non-invasive mechanical ventilation through a mask, ventilation through a tube into the windpipe, the administration of heated and humidified oxygen via a tube in the nose, or a heart-lung bypass.

The researchers stressed the importance of preventing secondary infections.

They noted that SARS-Cov-2 also invades the intestines, where it causes inflammation and leakiness of the gut lining, allowing the opportunistic entry of other disease-causing microorganisms.

The researchers advocate that this should be prevented with nutritional support, for example with probiotics -- beneficial bacteria that protect against the establishment of harmful ones -- and nutrients and amino acids to improve the immune defences and function of the intestine.

"Because treatment for now relies on aggressive treatment of symptoms, preventative protection against secondary infections, such as bacteria and fungi, is particularly important to support organ function, especially in the heart, kidneys, and liver, to try and avoid further deterioration of their condition," Liu added.

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Agencies
June 17,2020

Leading physicians are celebrating a small dose of good news that arrived Tuesday about dexamethasone, a cheap and widely used steroid shown to be able to save lives among COVID-19 patients, but also cautioning against releasing study results by press release during a global health emergency, like in the case of the latest dexamethasone study by University of Oxford.

"It will be great news if dexamethasone, a cheap steroid, really does cut deaths by one-third in ventilated patients with COVID19, but after all the retractions and walk backs, it is unacceptable to tout study results by press release without releasing the paper", Atul Gawande, surgeon and CEO of Haven Healthcare, tweeted.

"Bottom line is, good news," Dr. Fauci, America's foremost infectious diseases expert told a US newswire on Tuesday, soon after the dexamethasone results were announced in the UK.

Fauci, who has long championed the therapeutics-first view said that dexamethasone is a "significant improvement" in the available therapeutic options currently available.

On Medical Twitter and Facebook, doctors broadly agree that dexamethasone use aligns well with the way COVID19 attacks the body's immune system. Fauci said the results in the Oxford study make "perfect sense" in that context.

"We should see the number of people who actually survive go up, if the study holds up," virologist and epidemiologist Dr. Joseph Fair told a television network.

Global coronavirus cases crossed 8 million on Tuesday. In the US, Texas and Florida are facing a new wave of cases after lifting lockdown orders earlier than medical experts recommended. Amidst the relentless graph upwards, the dexamethasone study results injected hope for better survival rates among those most seriously ill.

World Health Organization chief scientist Soumya Swaminathan welcomed the results from the randomised control trial.

Dr Eugene Gu, Founder and CEO of CoolQuit tweeted that he is "genuinely impressed" with the UK dexamethasone trial. This may be a "game changer", he wrote.

"There's no conflict of interest as dexamethasone is a generic steroid. The mechanism of action makes sense because steroids can reduce cytokine storms and overactive immune systems that makes COVID-19 so deadly. The number needed to treat is 8 ventilated patients which is great."

The Oxford study found that dexamethasone reduced deaths by 35 percent in patients who needed treatment with breathing machines and by 20 percent in those only needing supplemental oxygen. Dexamethasone was one of 5 drugs studied in a large clinical trial in the United Kingdom named RECOVERY, short for Randomised Evaluation of COVID-19 Therapy.

Peter Horby, chief investigator of the University of Oxford clinical trial, said dexamethasone is the first drug to be shown to improve survival in COVID-19. Details of the study have not been released. The trial organisers said they made their announcement via a news release because of "the public health importance of these results." According to Horby's public comments, there was a lot of initial resistance to studying steroids.

During the study, 2,104 patients were randomly selected to be given 6 milligrams of dexamethasone once a day (either by mouth or by intravenous injection) for 10 days. That group was compared with 4,321 patients who received the usual care alone.

Researchers estimated that dexamethasone would prevent one death for every eight patients treated while on ventilators and one for every 25 patients on extra oxygen alone.

UK experts have called the study results a breakthrough in the fight against the virus. The researchers have promised they would publish the results soon.

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