Ivermectin is still not a miracle cure for COVID-19, despite what you may have read


Andrew McLachlan, University of Sydney

The head lice drug ivermectin has yet again been touted in the media as a possible treatment for COVID-19. But despite the favourable headlines, huge uncertainty remains about whether this treatment can be safely and effectively repurposed to tackle the coronavirus.

In recent weeks the media has been awash with claims ivermectin, when given in combination with the common antibiotic doxycycline and zinc supplements, is effectively a “cure” for COVID-19.

Yet there has been no definitive clinical trial so far showing this is the case. All we have are observational studies and clinicians’ opinions.

The World Health Organisation’s database of clinical studies for COVID-19 shows there are currently 16 trials investigating ivermectin. Even these studies are unlikely to provide the high-quality data necessary to show ivermectin can actually provide its touted benefits.

Many of the current studies have low numbers of participants, weak study designs, and inconsistent (and relatively low) ivermectin dosing regimes, with ivermectin frequently given in combination with other drugs.

The Royal Australian Council of General Practitioners and the Australian Commission for Quality and Safety in Health Care have warned there is insufficient evidence ivermectin is a safe and effective treatment for people infected with the coronavirus.

What do we know about ivermectin for COVID-19?

Laboratory studies using monkey cells in a test tube (as opposed to clinical studies in human patients) have shown ivermectin can shut down the replication of SARS-CoV-2, the coronavirus that causes COVID-19, within 24-48 hours of exposure to the drug.

Ivermectin is thought to inhibit the virus by preventing viral proteins moving in and out of the host cell’s nucleus, which is essential for replication of the coronavirus.




Read more:
Head lice drug Ivermectin is being tested as a possible coronavirus treatment, but that’s no reason to buy it


The problem is this process requires very high concentrations of ivermectin – well above the recommended dose for humans. This means ivermectin’s virus-killing powers would be unlikely to be harnessed inside the human body.

A detailed analysis of the relationship between dose and concentration of ivermectin suggests none of the currently used ivermectin dosing regimens would deliver high enough concentrations of ivermectin inside the body to activate its virus-killing effects.

Another review backs this up, suggesting all of the ivermectin doses being investigated in current clinical trials would fall well short of achieving drug concentrations high enough to wipe out SARS-CoV-2.

Even a 120 mg dose of ivermectin, which would be regarded as excessive (compared with the recommended dose of 3-15mg for treating parasitic infections) resulted in blood concentrations several orders of magnitude times lower than those needed to inhibit the virus.

Head louse on human hair
Great for killing head lice, but the jury’s still out on coronavirus.
GillesSM/Wikimedia Commons, CC BY-SA

How much ivermectin is too much?

While ivermectin generally doesn’t cause problematic side effects at the currently used doses, there is limited information about whether much larger doses would also be safe.

Repurposing ivermectin as a “cure” for COVID-19 would require massive doses, which would substantially increase the risk of side effects such as nausea, rash, dizziness, immune suppression, abdominal pain, fever, raised heart rate and unstable blood pressure.

Ivermectin at usual doses does not enter the central nervous system, but after large doses of the drug it may enter the brain, potentially causing impaired vision, hampering the central nervous system (which could in turn affect breathing, heart rate and consciousness), and exaggerating the effects of other sedative medicines such as benzodiazepines.




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Ivermectin is a hugely useful medicine in treating parasitic illnesses such as lice, worms and scabies, particularly in developing countries. But as we have already seen in the case of the malaria drug hydroxychloroquine, just because a medicine is useful for one purpose, it cannot automatically be considered a miracle cure for COVID-19.

Repurposing drugs as COVID-19 treatments

Repurposing existing drugs as possible COVID-19 treatments is a smart strategy, but requires several key principles to be addressed. The drug must have antiviral effects in cells and animals at doses relevant to humans. The drug must be able to get to the site of infection in the body (or reduce the inflammation associated with the infection). It is best if the antiviral mechanism is understood. And finally, well designed clinical trials are needed to be sure the drugs works in people with the infection and it is safe to use (especially in older, vulnerable unwell people).

Thankfully, Australia’s National COVID-19 Clinical Evidence Taskforce continually assesses and updates the best evidence-based advice for treating COVID-19, which you can read here.The Conversation

Andrew McLachlan, Head of School and Dean of Pharmacy, University of Sydney

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Is remdesivir a miracle drug to cure coronavirus? Don’t get your hopes up yet


Nial Wheate, University of Sydney and Andrew Bartlett, University of Sydney

The race is on to find a drug that is both effective and safe for treating COVID-19, which has spread to 3.1 million infections and caused 220,000 deaths worldwide.

This week, the US National Institute of Allergy and Infectious Diseases released findings of a clinical trial of the experimental antiviral drug remdesivir. This showed COVID-19 patients recovered more quickly and had an improved survival rate when taking the drug, compared with those given a placebo and standard care.

But these are just the preliminary results of one study. Other human trials have not shown similar results. Further trials are under way and will more definitively show whether remdesivir is a suitable and effective treatment for COVID-19.




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What is remdesivir?

Remdesivir is an experimental antiviral drug being developed by Gilead Sciences. Originally it was being developed as a treatment for Ebola, a viral infection that causes severe internal bleeding. But researchers are now interested in its potential to treat patients with COVID-19.

Remdesivir mimics a natural ingredient called adenosine of DNA and RNA, the latter being a molecule similar to DNA that is used to carry the genetic information of viruses. After the drug is activated in the body, it works by blocking a type of enzyme called a polymerase, which is needed to make DNA and RNA.

When you block the enzyme, the virus can’t make copies of itself, limiting the development of symptoms and spread of the disease.

It should be noted that no drug is perfectly safe, and remdesivir is no different. Studies undertaken so far suggest the drug may damage the liver and cause other short-term side effects such as nausea and vomiting.

These side effects need to be taken into consideration when treating COVID-19 patients who have other underlying conditions.

Clinical trials in US positive but only preliminary

This week the National Institute of Allergy and Infectious Diseases (NIAID) released the results of its trial using remdesivir for COVID-19 patients. They studied the effects of the drug on patients who were already infected with COVID-19 to see whether it helped them recover faster and improve their survival rate.

Adult patients hospitalised with COVID-19 were given daily injections of remdesivir. They were found to recover four days faster, an improvement of 31%, when compared with other patients who only received standard care and placebo.




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The results also indicated that more patients survived the infection with remdesivir treatment, with the death rate dropping from 11.6% to 8%.

The results are significant enough that director of NIAID Anthony Fauci said it was an “ethical responsibility” for the remaining trial patients who were taking the placebo to be switched to the active drug.

But we need to treat the results of this trial with caution; for the moment they are only preliminary.

A data and safety panel has looked at the initial results, but they haven’t been peer-reviewed. During peer review, independent experts from the scientific community scrutinise the study design, methods, data produced, and the conclusions before the study is published in a medical journal.

How does it compare with other studies?

The results of other trials, such as one undertaken in China, have not shown the same promising results.

The Chinese study was published in the Lancet, considered one of the most influential medical journals in the world. This trial was a randomised, double-blind, placebo-controlled study which means that neither the researchers nor the patients knew if they’d been given the active drug or a placebo.

These types of studies can reduce some biases that can influence studies, but also help quantify the effectiveness of the drug.

But the study also had limitations that need to be recognised. The patients were not as seriously ill as those in the NIAID trial, and the study was terminated early because the outbreak in China was easing.

In the end, the study only collected data on 237 patients, compared with 1,063 patients in the NIAID trial. The authors acknowledge further study is needed in more seriously ill patients and with a larger sample size.

Currently there are more than a dozen other clinical trials of remdesivir and COVID-19 being undertaken throughout the world. We need to await the data to know for sure whether the drug is as effective as we need it to be.




Read more:
Head lice drug Ivermectin is being tested as a possible coronavirus treatment, but that’s no reason to buy it


This article is supported by the Judith Neilson Institute for Journalism and Ideas.The Conversation

Nial Wheate, Associate Professor | Program Director, Undergraduate Pharmacy, University of Sydney and Andrew Bartlett, Associate Lecturer Pharmacy Practice, University of Sydney

This article is republished from The Conversation under a Creative Commons license. Read the original article.

We have a vaccine for hepatitis B but here’s why we still need a cure



Around 5% of adults and 90% of babies who contract hepatitis B go on to have life-long infection that can only be managed with regular medication.
Ronald Rampsch/Shutterstock

Peter Revill, The Peter Doherty Institute for Infection and Immunity and Margaret Littlejohn, Melbourne Health

Hepatitis B is blood-borne virus that packs a punch. Worldwide, more than 1.3 billion people have been infected with hepatitis B, and 257 million people have developed a life-long infection. This includes 240,000 Australians, many of whom are Indigenous.

Globally, transmission most commonly occurs from mother to baby or in early life. But it’s possible to be infected in adulthood, through sex or blood-to-blood contact.

Most people who are infected in adulthood develop a short infection which their immune response controls. But in around 5% of adults and 90% of babies, the immune response is ineffective and chronic infection develops.




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Hepatitis B virus causes almost 40% of all liver cancer, which is the fifth most common cancer and the second leading cause of cancer-related death worldwide.

Australian discovery

Hepatitis B virus was discovered in the serum of an Indigenous Australian in 1965 and was first known as the “Australia antigen”.

This quickly led to the development of an effective vaccine in the 1980s, which is now available worldwide. The vaccine has been given to Australian infants since May 2000.

(If you weren’t vaccinated as a baby, you might want to consider doing so through your GP, particularly if you plan to travel to Asia and Africa where hepatitis B is common.)

Unfortunately the vaccine doesn’t do anything for the 240,000 or so Australians who currently live with chronic hepatitis B. Only around 60% of these people have been diagnosed; the rest don’t know they’re infected and don’t receive appropriate care.

How is it currently treated?

There is no cure for chronic hepatitis B virus.

In most cases, treatment requires taking a pill every day for life to remain effective and to reduce the risk of liver cancer. Even then, it doesn’t eliminate the risk.

Chronic hepatitis B hasn’t been cured so far in part because current therapies have failed to destroy the viral reservoir, where the virus hides in the cell.

This is in contrast to hepatitis C virus, which has no such viral reservoir and can now be cured with as little as 12 weeks of treatment.




Read more:
In contrast to Australia’s success with hepatitis C, our response to hepatitis B is lagging


Despite the huge human and economic toll of chronic hepatitis B, research to cure the disease remains underfunded. There is a misconception that because there is a vaccine, hepatitis B is no longer a problem.

The availability of effective cures for the unrelated hepatitis C virus has also led people to believe that “viral hepatitis” is no longer a problem.

Experts estimate that liver cancer deaths will substantially increase in coming decades without a cure for hepatitis B, despite deaths from most cancers decreasing.

Hepatitis B causes 40% of all liver cancer.
Napocska/Shutterstock

How far have we got?

Some exciting research is underway around the world, including the recent identification of the “cell receptor” which allows the virus to infect the body. This has enabled studies of the complete virus replication cycle including the viral reservoir that is untouched by current therapies.

New approaches to a possible cure include mechanisms to block the virus’ entry into the cell and to stop the virus from making the proteins it needs to replicate and infect new cells.

Studies are also underway to enhance patients’ immune responses so their own natural defences can control or even eliminate the virus. This is similar to immunotherapies already being used to treat some cancers.




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Explainer: the A, B, C, D and E of hepatitis


It’s likely a hepatitis B cure will require a dual-pronged approach, directly targeting the virus while also enhancing the immune response in people who are infected.

The goal is to reduce the amount of virus in the body and restore the person’s immune responses. This is called a “functional cure” and is similar to what happens when a person naturally gets rid of the virus. It would also mean they didn’t need to take drugs any more.

Some of these approaches are now in early stage human clinical trials. More than 30 drugs have been developed and are being tested in people with chronic hepatitis B. However, much more work needs to be done to achieve a cure.The Conversation

Peter Revill, Senior Medical Scientist at VIDRL, Royal Melbourne Hospital, The Peter Doherty Institute for Infection and Immunity and Margaret Littlejohn, Medical Scientist, Melbourne Health

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Anti-Christian Sentiment Marks Journey for Bhutan’s Exiles


Forced from Buddhist homeland, dangers arise in Hindu-majority Nepal.

KATHMANDU, Nepal, February 23 (CDN) — Thrust from their homes in Bhutan after Buddhist rulers embarked on an ethnic and religious purge, Christian refugees in Nepal face hostilities from Hindus and others.

In Sunsari district in southeastern Nepal, a country that is more than 80 percent Hindu, residents from the uneducated segments of society are especially apt to attack Christians, said Purna Kumal, district coordinator for Awana Clubs International, which runs 41 clubs in refugee camps to educate girls about the Bible.

“In Itahari, Christians face serious trouble during burials,” Kumal told Compass. “Last month, a burial party was attacked by locals who dug up the grave and desecrated it.”

Earlier this month, he added, a family in the area expelled one of its members from their home because he became a Christian.

Bhutan began expelling almost one-eighth of its citizens for being of Nepali origin or practicing faiths other than Buddhism in the 1980s. The purge lasted into the 1990s.

“Christians, like Hindus and others, were told to leave either their faith or the country,” said Gopi Chandra Silwal, who pastors a tiny church for Bhutanese refugees in a refugee camp in Sanischare, a small village in eastern Nepal’s Morang district. “Many chose to leave their homeland.”

Persecution in Bhutan led to the spread of Christianity in refugee camps in Nepal. Though exact figures are not available, refugee Simon Gazmer estimates there are about 7,000-8,000 Christians in the camps – out of a total refugee population of about 85,000 – with many others having left for other countries. There are 18 churches of various faiths in the camps, he said.

“Faith-healing was an important factor in the spread of Christianity in the camps,” said Gazmer, who belongs to Believers’ Church and is awaiting his turn to follow five members of his family to Queensland, Australia. “A second reason is the high density in the camps.”

Each refugee family lives in a single-room hut, with one outdoor toilet for every two families. The Nepalese government forbids them to work for fear it will create unemployment for local residents.

Life was even harder for them before 2006, when Nepal was a Hindu kingdom where conversions were a punishable offence.

“When I began preaching in 2000, I had to do it secretly,” said Pastor Silwal of Morang district. “We could meet only surreptitiously in small groups. I used my hut as a make-shift church while many other groups were forced to rent out rooms outside the camp.”

A fact-finding mission in 2004 by Brussels-based Human Rights Without Frontiers found that police pulled down a church structure built by Pentecostal Christians in the Beldangi camp by orders of Nepal’s home ministry. The rights group also reported that Hindu refugees ostracized the Christians, who had proceeded to rent a room outside the camp to meet three times a week for worship services and Bible study.

When the Jesus Loves Gospel Ministries (JLGM) organization sent officials from India to the Pathri camp in Morang in 2006, they found that local residents resentful of the refugees had taken note of a baptism service at a pond in a nearby jungle.

“In August, we were planning another baptism program,” JLGM director Robert Singh reported. “But the villagers put deadly poisonous chemicals in the water … Some of the young people went to take a bath ahead of our next baptism program. They found some fish floating on the water and, being very hungry – the refugees only get a very small ration, barely enough to survive on – they took some of the fish and ate them. Three of them died instantly.”

Singh also stated that poisoned sweets were left on the premises of the refugee school in the camp. They were discovered in time to avert another tragedy.

Life for Christian refugees improved after Nepal saw a pro-democracy movement in 2006 that caused the army-backed government of Hindu king Gyanendra Bir Bikram Shah to collapse. The king was forced to reinstate parliament, and lawmakers sought to curb his powers by declaring Nepal a secular state.

Though Christian refugees are now allowed to run churches openly in the camps, ill will toward them has yet to end. When Pastor Silwal asked camp authorities to allow him to open a church in 2006, Hindu neighbors protested, saying it would cause disturbances. Camp authorities allowed him to open a tiny church in a separate room on the condition that its activities would not disturb neighbors.

Earlier in his life in Bhutan, said the 40-year-old Pastor Silwal, he had been a stern Hindu who rebuked his two sisters mercilessly for becoming Christians. He forbade them to visit their church, which gathered in secret due to the ban on non-Buddhist religions in place at the time. They were also forbidden to bring the Bible inside their house in Geylegphug, a district in southern Bhutan close to the Indian border.

“I became a believer in 1988 after a near-death experience,” Pastor Silwal told Compass. “I contracted malaria and was on the verge of death since no one could diagnose it. All the priests and shamans consulted by my Hindu family failed to cure me. One day, when I thought I was going to die I had a vision.”

The pastor said he saw a white-robed figure holding a Bible in one hand and beckoning to him with the other. “Have faith in me,” the figure told him. “I will cure you.”

When he woke from his trance, Silwal asked his sisters to fetch him a copy of the Bible. They were alarmed at first, thinking he was going to beat them. But at his insistence, they nervously fetched the book from the thatched roof of the cow shed where they had kept it hidden. Pastor Silwal said he tried to read the Bible but was blinded by his fever and lost consciousness.

When he awoke, to his amazement and joy, the fever that had racked him for nearly five months was gone.

Pastor Silwal lost his home in 1990 to the ethnic and religious purge that forced him to flee along with thousands of others. It wasn’t until 1998, he said, that he and his family formally converted to Christianity after seven years of grueling hardship in the refugee camp, where he saw “people dying like flies due to illness, lack of food and the cold.”

“My little son too fell ill and I thought he would die,” Silwal said. “But he was cured; we decided to embrace Christianity formally.”

Homeless

In 2001, Bhutan4Christ reported the number of Bhutanese Christians to be around 19,000, with the bulk of them – more than 10,500 – living in Nepal.

When persecution by the Bhutanese government began, frightened families raced towards towns in India across the border. Alarmed by the influx of Bhutanese refugees, Indian security forces packed them into trucks and dumped them in southern Nepal.

Later, when the homesick refugees tried to return home, Indian security forces blocked the way. There were several rounds of scuffles, resulting in police killing at least three refugees.

Simon Gazmer was seven when his family landed at the bank of the Mai river in Jhapa district in southeastern Nepal. Now 24, he still remembers the desolation that reigned in the barren land, where mists and chilly winds rose from the river, affecting the morale and health of the refugees. They lived in bamboo shacks with thin plastic sheets serving as roofs; they had little food or medicine.

“My uncle Padam Bahadur had tuberculosis, and we thought he would die,” said Gazmer, who lives in Beldangi II, the largest of seven refugee camps. “His recovery made us realize the grace of God, and our family became Christians.”

The plight of the refugees improved after the U.N. High Commissioner for Refugees (UNHCR) stepped in, receiving permission from the government of Nepal to run the refugee camps. According to the UNHCR, there were 111,631 registered refugees in seven camps run in the two districts of Jhapa and Morang.

Though Nepal held 15 rounds of bilateral talks with Bhutan for the repatriation of the refugees, the Buddhist government dragged its feet, eventually breaking off talks. Meantime, international donors assisting the refugee camps began to grow weary, resulting in the slashing of aid and food. Finally, seven western governments – Canada, Norway, Denmark, New Zealand, Australia, the United States and the Netherlands – persuaded Nepal to allow the refugees to resettle in third countries.

The exodus of the refugees started in 2007. Today, according to the UNHCR, more than 26,000 have left for other countries, mostly the United States. A substantial number of the nearly 85,000 people left in the camps are ready to follow suit.

Although they now have a new life to look forward to, many of Bhutan’s Christian refugees are saddened by the knowledge that their homeland still remains barred to them. So some are looking at the next best thing: a return to Nepal, now that it is secular, where they will feel more at home than in the West.

“I don’t have grand dreams,” said Pastor Silwal. “In Australia I want to enroll in a Bible college and become a qualified preacher. Then I want to return to Nepal to spread the word of God.”  

Report from Compass Direct News