Ask a room full of people any of the above and a lot of hands would go up. They would, of course, all be wrong. The reasons are relatively simple and straightforward, the logic undeniable and yet millions of Americans still pursue these drugs, in some instances forfeiting their lives in the process.

To understand why the evidence for the success of these drugs as a treatment for Covid isn’t compelling, we need to establish a few facts first. For instance, take the following question. Just how much risk is there of Covid killing you? It seems like a simple question to answer, but in truth, it is anything but.

Case Fatality Rates, CMR, and IFR

The probability that someone dies from a disease doesn’t just depend on the disease itself, but also on the treatment they receive, and on the patient’s own ability to recover from it. This makes interpreting data complex and very nuanced.

Catching SARS-CoV2 and developing Covid isn’t a death sentence, not for most of the people who contract it. Global figures based on PCR testing reflect over 222 million cases to date. Of these cases, 4.5 million have proved fatal. The press will tell you this works out roughly at a risk ratio of around 2%, commonly referred to as the Case Fatality Rate (CFR), where the number of deaths is divided by the number of cases. The press is wrong.

Not to be confused with the Crude Mortality Rate (CMR), CFR is far from perfect in determining your personal risk from Covid. There are a few problems using CFR, the most obvious being the reported number of infected in a population. Cases could underreport infections as not everyone is tested and some patients present as asymptomatic (no symptoms).

CFR can decrease or increase over time, as responses change; and that it can vary by location and by the characteristics of the infected population, such as age, or sex. For instance, older populations would expect to see a higher CFR from COVID-19 than younger ones. For similar reasons, the Crude Mortality Rate or CMR is also not a reliable indicator.

So if neither the CFR nor CMR are a good indicator for risk, where do we turn. The scientific community (not the press and media) uses another measure called the Infection Mortality Rate, or IMR. This is the number of deaths from a disease divided by the total number of cases. If 10 people die of the disease, and 500 actually have it, then the IFR is [10 / 500], or 2%.

Confused?

To work out the IFR, we need two numbers: the total number of cases and the total number of deaths, but some of you may already have figured out that we don’t know the true number of cases and probably never will. We cannot test everyone and many are, as discussed earlier, asymptomatic, so researchers will use a ‘best guess’ in their calculation. Far from ideal, but we have no other method.

Despite what some press and media reports imply, the CFR is not the same as, or, even similar to the IFR. If the CFR is 2% then in reality the IFR for Covid will be far lower. For the purposes of this piece, let’s assume it to be 1%. For every 100 confirmed Covid cases, 1 patient will die.

And that is where the rub lies for treatments of the infection, particularly treatments that rely on early-stage administration. Drugs like hydroxychloroquine and ivermectin and treatments like monoclonal antibody infusions. It is only possible to tell if these drugs work in a clinical setting.

Pepsi® is the miracle cure

If all the 100 infected patients were to self-administer Pepsi® at home, 99 would statistically survive and 1 patient would die. People would sing the praises of Pepsi® and stores would be looted as a naive population stockpiled Pepsi®, just in case. The unfortunate patient who died would have had to stop drinking Pepsi®. Being intubated has its drawbacks.

The press and general public would of course be able to extrapolate these data and expand them to reach the following conclusions. Pepsi® is effective against Covid, offering you up to 99% protection. It isn’t an effective treatment in the late stages of the disease, so make sure you order your Pepsi® early from Americas’ Frontline Doctors (AFLDS). Sound familiar?

Obviously the above is an analogy, please don’t rush out and buy Pepsi® in the mistaken belief it will help your body combat Covid. The point is that exactly the same principle applies to ivermectin and hydroxychloroquine. If 99 out of 100 people were going to survive no matter what, then arguably you could ascribe their recovery to literally anything, including Pepsi®, Coke, Dr. Pepper’s, or tap water.

There are however mouth-watering sums of money to be made out of a gullible public that has in large part lost confidence in the system. A public that is in many ways its own worst enemy, spreading news of miracle cures online and belittling science and themselves in the process.

If you are one of the true believers, I hope you’re still reading and I’d recommend reading the above again. Let it really sink in.

Clearly, this problem isn’t merely limited to ivermectin and hydroxychloroquine. It affects all early-stage treatments and there are carefully controlled situations where the real efficacy of the treatments can be assessed and monitored, but these are also fraught with pitfalls.

Is there any way of proving that drugs or treatments do help?

Yes and no. Speak to almost any frontline doctor that’s been embedded in the Covid wards since the start of the pandemic and they’ll tell you the following. HCQ and ivermectin make no difference to the mortality rate of patients in their wards.

This, you can correctly argue, could simply be because the patient is too far gone by the time they are admitted for the drugs to have any effect. True, but in that case, please refer to the preceding argument.

Ideally, patients would need to be identified in the early stages of infection, treated with the drugs, and then have the viral load in their systems monitored. This method assumes that we have established viral loads across all patient populations and variants. We cannot identify deviations from the disease’s natural progression without these control data.

Sadly, a trial of this nature would be unable to correctly identify if the treatments actually ‘cure’ the patient or if they simply speed up the patient’s natural ability to recover. Something, let’s remind ourselves, 99 out of 100 were going to do in any case. Again, this problem isn’t mutually exclusive to ivermectin and HCQ, it affects the assessment of all Covid treatments.

To be able to confirm without a doubt that a treatment is effective against the onset of death from Covid, the treatment would need to prove effective in reducing mortality in admitted patients. That is the gold standard and doctors will tell you, it doesn’t apply to either ivermectin or hydroxychloroquine.

Sorry.

Vaccines however do work. That 1% can be reduced to 0.05% if you simply get vaccinated. That’s a proven fact.

The post The Simple Truth Ivermectin and HCQ Supporters Fail to Acknowledge appeared first on Medika Life.

We Americans have a long and glorious history of snake oil salesmen. There is always someone peddling useless — and sometimes harmful — concoctions when there’s sickness and suffering. John D. Rockefeller’s father was just such an itinerant quack. What finer pedigree could you ask for?

It should be no surprise then that here in the US of A, we’ve taken the most dubious claims of hydroxychloroquine’s effects on COVID-19 and hyped them from the highest podium in the land: “What do you have to lose?”.

Aside from the shame of snake oil salesmen being encoded into the DNA of our country is the fact that Americans always seem eager to buy what the shameless hucksters are selling.

And then, there’s the question of the snake oil itself. The stuff in the bottle. What is it anyway?

What is hydroxychloroquine, and where does it come from?

The short answer is that hydroxychloroquine is a modification of an earlier drug called chloroquine, which in turn is a synthetic version of a natural drug derived from tree bark that many of us have heard of, called quinine. Quinine has a veeery long history as an antimalarial drug. Still, it is also commonly known as an additive in tonic water (as in gin and tonic), giving it its characteristic bitter taste. Quinine is a plant alkaloid. Alkaloids can be toxic and are known for their bitterness. Think of caffeine — a classic alkaloid.

With some very smart commentators blogging on current issues with these drugs (Derek Lowe on the Science Magazine website is particularly good).

Despite the fun of digging into that black hole of technical information, I thought the back story was even more interesting.

Countess Ana de Osorio

It all starts with Ana de Osorio, wife of Luis Jeronimo de Cabrera, Count of Chinchon and importantly, Viceroy of Peru from 1629 to 1639.

I love the names and titles.

Ana de Osorio, Countess of Chinchon…

In 1638, the story goes, Ana de Osorio became very sick from malaria. The governor of Loxa wrote to the viceroy claiming to have been cured by the bark of the quinaquina tree. The governor was summoned, the medicine administered, and Ana was cured. Ana returned soon after to Spain bringing this miraculous bark of the tree eventually named after her as the Cinchona tree.

It turns out that this story, documented in 1663 by an Italian, Sebastiano Bado, was wrong on most counts and was disproved by the discovery in 1930 of the Viceroy’s official diary.

It turns out, for example, that Ana, the first Countess of Chinchon, died three years before Luis even went to Peru as viceroy. The second Countess of Chinchon, who did accompany Luis, was the picture of health the whole time but died on the journey from Peru back to Spain. But the (mis)story of Ana de Osorio persists to this day, like a virus that has become integrated into the DNA of our culture.

The Cinchona Tree

The bark of the Cinchona tree nonetheless bent the curve of medical and human history. It was brought by Jesuit priests to Europe, where the Spanish apparently knew of the bark’s medicinal value as early as the 1570s and was first used to treat malaria in Rome in 1631 (long before the mythical Ana even fell ill).

This bark, also called Jesuit’s bark or Peruvian bark at the time, became one of the most valuable exports from Peru when it became clear that it successfully treated malaria patients in Rome. Rome was once surrounded by marshes, and the name malaria comes from the medieval Italian words mala (bad) and aria (air). Malaria was associated with “bad air” emanating from Roman swamps.

Today we know that the cause of the disease is a single-celled parasite, Plasmodium falciparum, carried by mosquitoes that are endemic to marshlands.

Bad Air

Bad air was typically what Western medieval people blamed for any kind of disease. This was consistent with the ‘miasmic theory,’ passed down almost unchanged from ancient Greece a couple of millennia before. Microscopic organisms were not even known until Robert Hooke published his findings on them in 1665, followed soon after by Anton van Leeuwenhoek’s observations with his famous homemade microscopes. The role played by some of these microorganisms in human disease was still not recognized until Louis Pasteur’s experiments in the 1860s and Lister’s treatise on antisepsis which was published in 1867. Too late to mitigate the savagery of the American Civil War, which killed 2% of the population, most from disease (like malaria) and infection (doctors did not wash their hands or otherwise use aseptic technique while sawing off soldier’s mangled limbs).

But back to Rome, where malaria killed indiscriminately. Popes, cardinals, priests, and many other Romans — rich and poor — died miserably from the disease. The Jesuit’s knowledge of this bark’s curative abilities eventually led to its explosive rise in value and demand throughout 17th and 18th century Europe.

The Peruvian quinaquina tree eventually yielded a purified drug, the active ingredient called quinine, in 1820. Pierre Joseph Pelletier and Joseph Bienaime Caventou, French chemists who discovered caffeine and strychnine, among many other alkaloid plant compounds, found quinine was the active ingredient in the Peruvian tree bark.

Colonial Drugs

Quinine used as a drug enabled Europeans to colonize Africa. Native Africans had evolved certain traits associated with sickle-cell anemia and other genetic diseases, which gave them some resistance to malaria. Europeans did not have these genetic characteristics and were much more susceptible to the parasite. Africa became known as the White Man’s Grave. Quinine rectified that genetic deficiency and led to Europe rapidly colonizing and chopping up Africa in a global game of Risk.

The European’s colonial drive took them around the world, and quinine clearly enabled their global competition for territory, resources, and subjects, especially in equatorial and malaria-infested regions of the world. Although quinine is credited with saving many millions of lives over the centuries, one of the unintended consequences was that it enabled the Western powers’ colonial ambitions and conflicts, thus setting the stage for the slaughterhouse of World War I and its domino effect of WWII.

Quinine’s bitterness spurred British officials in various early 19th century colonial outposts to mix their medicine with soda and sugar — which marked the origin of tonic water. The British in colonial India mixed their tonic water with gin, creating a classic cocktail that is still embedded in our culture to this day.

The value of quinine rose rapidly, causing Jesuit’s bark to focus on global games of Risk and Monopoly. Peru and the neighboring countries tried to corner the market for their native Cinchona trees, but the Dutch managed to smuggle seeds out of South America. Eventually, Dutch plantations in Indonesia became the dominant world suppliers. The wily Dutch outplayed the South Americans and ended up with 97% of the global market and set up a quinine cartel in 1913 to control global supply and prices.

The 20th Century Drug

Quinine played a key role in one of the biggest successes and engineering marvels of the 20th century — the Panama Canal, built between 1904–1914 — driven by the big stick policies and willfulness of Teddy Roosevelt. There were many reasons for the failure of the early French efforts to build a canal across Central America. Still, the immense casualty rate among the engineering and labor forces certainly played a key role in France abandoning the project to the Americans.

Tropical diseases such as malaria were a major if not top contributor to French casualties. Central to the success of the American project was the groundbreaking public health initiatives driven by Dr. William Gorgas and his team — and their application of a new scientific understanding of malaria and other tropical diseases being transmitted by mosquitos. Mosquito control and prophylactic administration of quinine were among the cornerstones of their efforts.

Malaria also played an outsized role in the number of casualties during the First World War (disease — not the enemy — was usually the main killer of soldiers in wars throughout history). Before WWI, scientists and public health experts successfully controlled malaria in parts of Europe like Italy and Greece. However, these public health measures lapsed during the war, and also afterward: malaria became a global scourge again, well into the 20th century. Prophylactic use of quinine was studied and implemented by some countries during the Great War.

The late 19th and early 20th century were a sort of golden age of synthetic and organic chemistry, and quinine played a Muse’s role in this. Chemists tried to synthesize quinine since it was an expensive natural product (remember the Dutch cartel). Their efforts often failed miserably — but in a classic example of experimental serendipity — the failures sometimes bore fruit. William Perkin’s attempt in 1856 to make quinine resulted in abject failure and a mess, but the mess yielded a brilliant purple dye which made him a fortune. He was 18 years old.

The Age of Synthetics

Synthetic organic dyes, triggered by Perkin’s success, were one of the economic foundations of the German economy. Starting in the late 1860s, well-known companies formed that exists to this day: Bayer, BASF, Hoechst, etc.

A number of dyes were proposed as treatments for malaria, including methylene blue developed by Paul Ehrlich in 1890 and first used by him to treat malaria patients in 1891. Aside from not being as effective as naturally derived quinine, the dye-based malaria drugs had the unfortunate side effect of turning patients into various unnatural colors.

Finally, Hans Andersag, a researcher at Bayer AG in Germany, discovered a synthetic version of quinine in 1934 which eventually became known as chloroquine. Bayer ran clinical trials of these drugs in North Africa in the early 1940s during WWII, and this information fell into Allied hands around 1943. US doctors eventually recognized the efficacy of chloroquine, and it was approved for clinical use in the US in 1947.

During WWII, millions of US soldiers were given prophylactic antimalarial regimens, which resulted in a very unexpected and positive side effect. Clinicians noted reduced symptoms in those suffering inflammatory disorders such as skin rashes and some forms of arthritis after taking the drug. Clinical trials subsequently demonstrated the efficacy of antimalarials for a range of inflammatory diseases, starting with systemic lupus erythematosus in 1951. Today chloroquine analogs are administered off-label (i.e., not approved by the FDA) for a wide range of autoimmune diseases since they are among the few effective treatments that reduce symptoms. However, we still do not know exactly how chloroquine-based drugs blunt inflammation.

Another positive outcome of WWII was more organizational. The Office of Malaria Control in War Areas, established in 1942, was the immediate predecessor of the CDC, which was first known as the Communicable Disease Center when it kicked off on July 1, 1946. Malaria was the first target on its project roster, with the National Malaria Eradication Program starting a year after the CDC’s founding. Success was declared by 1951. Spraying DDT was one of the cornerstones of the CDC’s efforts to eradicate the mosquito vector of malaria, while chloroquine was the cornerstone of prophylaxis and treatment of the disease.

Where We Are Today

Hydroxychloroquine is a modification of chloroquine where a hydroxyl group (-OH) was appended to the side chain to reduce toxicity and was approved for medical use in the US in 1955.

In the years since chloroquine and hydroxychloroquine were approved in the US, we’ve learned a few things about these antimalarial drugs. We know now that these drugs accumulate in lysosomes and inhibit their acidification, which has subsequent effects on a range of cellular processes, including antigen presentation. We know these drugs reduce cytokine production by macrophages and inhibit toll-like receptor signaling and a variety of other immune pathways. But we remain far from causally linking the drugs to these disparate biological effects or ultimately to their clinical efficacy (against malaria or various inflammatory diseases).

Our long history of using these drugs has given us some insights into their limitations, side effects, and adverse drug interactions. One of the more severe side effects includes QT prolongation, an electrical disturbance of the heart that can lead to a fatal arrhythmia. Another is a 30% mortality among patients administered hydroxychloroquine who also took metformin, an important anti-diabetic drug.

In the US, malaria is no longer a significant clinical problem. But hydroxychloroquine and its analogs are prescribed for a wide range of debilitating autoimmune diseases, and many patients have come to rely on these drugs.

Then in 2020, dubious and poorly executed clinical studies hyped the effects of hydroxychloroquine and falsely claimed this drug had beneficial effects on COVID-19 patients. Didier Raoult, who masterminded these efforts, has since been censured and his papers retracted.

No placebo-controlled, double-blinded, sufficiently-powered clinical studies show hydroxychloroquine works against COVID-19.

Diabetics have a worse outcome with COVID-19, and these patients likely take metformin which is known to have lethal interactions with hydroxychloroquine.

In the rest of the world, over a million people per year, mostly pregnant women and young children, still die from malaria. But in a typical display of poorly allocated healthcare capital, we spend more on baldness treatments than for antimalarial treatments. Drug resistance has become a significant problem in many parts of the world so the need to invest in more antimalarial drug development is acute — but we still mostly use drugs that are almost a century old.

We’re gradually learning more and more molecular details of the intricate and complex life cycle of Plasmodium falciparum, the malaria parasite. Here are a couple of beautiful animations that show how malaria moves through the human host in one video and in the mosquito host in the other.

Molecule Allows Malaria Parasite to Commandeer Red Blood Cells
Two groups of HHMI scientists working independently have identified a critical enzyme that allows a malaria-causing…www.hhmi.org.

I don’t think there is anyone left who believes hydroxychloroquine works against COVID-19. If there are, if it is you, don’t be the last sucker buying snake oil. Instead, get vaccinated against COVID-19. Today.

The post The Evolution of Quinine to Hydroxychloroquine, Covid’s Snake Oil appeared first on Medika Life.