Antibiotic Resistance Crisis P2: The Battle

My previous article was about the basics of antibiotic use and that it is an Art to fight the Antibiotics War against bacteria. How we can use Nuclear bombs, but probably hurt innocent bacteria. That we want snipers that know where and how to kill them. And that we were lucky in 1928: the first antibiotic literally flew into our lives to save us from these tiny terrorists, his name: Cillin, Penicillin. 

In this second article about Antibiotic Resistance we will focus on the actual Battle.

Intra-Bellum

When did this Battle start, I hear you asking? You might think it started close to 1928. That we started curing people almost immediately, right? Well, no. Humanity wouldn’t be humanity if we didn’t wait for 15 years to introduce Penicillin. Three years after the first bacteria became resistant to it. Already 0-1 behind.
Researchers from Oxford were working hard to make a working, safe and producible medicine of Penicillin, but it wasn’t easy. After years of research, they eventually had to reach out to the corn farmers from USA to help them bottle the precious mold juice that was the Antibiotic. Around 1941 the production started on a small scale. Like the BBC said in 1942: “Good science is not often quick in getting results.”

Mankind finally kicked back with Penicillin during a genuine real-life battle. The year was 1943, it was World War II. You probably heard about it, it was a pretty big war. What you probably did not hear before is that during the War soldiers could die from a simple splinter. While fighting a World War, we were still losing the Small Wars inside our body.

Fake news? Who cares!

It was probably thanks to some fake news and proper propaganda Penicillin came to the allied forces in 1944. And it involved Churchill. You know, 69 years old, overweight, heavy smoker, avid drinker. Well, he got a pneumonia in December 1943 and got pretty sick. Aaah. But he got saved. Yeah. So far, this is true. But then came the propaganda for Penicillin in the newspapers, here we go:

1. When Churchill was a boy (true, he once was a boy),
2. a man had saved him from drowning (not true)
3. Churchill’s father was so grateful that he paid for the hero’s son to attend medical school (also not true, never met him in his life).
4. That son, Alexander Fleming, discovered Penicillin that saved Churchill’s life (also, sorry, not true, he didn’t even get Penicillin).
5. And Churchill lived happily ever after (Well, he died in 1965, so not true).

And even though Churchill may not really have been helped by Penicillin, the propaganda helped the industry to get a move on things. In March 1944, 18 months after the BBC had reminded its listeners that good science goes slow, a factory began pouring out penicillin. 

Sex on the beach (well, probably after getting of the beach)

If you realize that in WW I 50,000 soldiers died from infectious diseases versus 1,265 during WW II where twice as many people fought, you understand why Penicillin was called a Wonder Drug. On June 6, 1944, allied soldiers carried that Penicillin with them onto the beaches of Normandy, benefitting 100,000 or so soldiers from that day.
And wow, that was a good call. After getting of the beach, the soldiers had a little bit too much trauma-relief-sex at the time. They got infected with Syphilis and Gonorrhea and yes, these could be cured by Penicillin. There were actual discussions going on where to introduce the antibiotic first, on the battlefield or in the bordello.
German soldiers probably experienced similar levels of sexual transmitted infections, but they had no remedy. Some theories go that the resulting advantage in troop strength may have tipped the balance of the war in favor of Allied forces during key engagements late in the war. Yeah, I know, but I did say it was a theory…

Introducing the beta lactam family
After the war ended, when everyone that was not dead or heavily traumatized returned to their homes, scientists were able to proof that the medicine was safe and working. Not all bacteria could be killed by the Penicillin, so they started their research on broadening the spectrum by adding stuff on Penicillin making it stronger and able to kill other bacteria as well. Think of The Incredibles meets Fantastic Four.  A whole family of Penicillin cored antibiotics emerged called: beta-lactam antibiotics. A Super Hero family that changed our lives for years.
A family however, that is also under severe threat by a Super Intelligent Army that chances the Rules of the War against Terrorist Bacteria: Antibiotic Resistance.

Next week, in the last episode of the Antibiotic Resistance crisis, Part 3:  Ugly fights, ugly truths.

Advertisement

Antibiotic Resistance Crisis P1: The Art of Antibiotic Warfare by Sun Tzu Bierhoff

This is the first article in the trilogy of antibiotic resistance. Let’s take a look at some basic rules of Antibiotics, how to use them and how we got them in the first place.

Fact 1: Antibiotics kill bacteria! Not viruses (like flu), not parasites (like your ex-wife or ex-husband), just bacteria.

Super simple and easy to understand. Well, not in practice, not in the daily healthcare. An example:

The common cold and the flu are caused by viruses. Are they killed by antibiotics? … (did you shout it out?) Indeed, NO! Many people ´suffering’ from these viruses visit their doctors and demand antibiotics. Or in some countries they just go to a pharmacy to buy some themselves. Kudos for their assertiveness, major penalty points for their solution. It won’t help. In fact, it can cause a lot of damage in both the short term – their own health is at risk – and the long term: antibiotic resistance.

Fact 2: You, yes you, carry millions of bacteria in your body and that’s ok, you need them.

When they stay in their designated places, bacteria are fine. It is only when they travel that they can cause problems. For instance, bacteria from your bowels can cause urinary tract infections and bacteria from your mouth causes pneumonia. So, some of the “bad bacteria” are also “good bacteria”, all at the same time. And we never want to kill the good guys, right?
This is where the struggle begins in Antibiotic warfare.

Nuke’m or shoot’m

Picture a bacterial infection as having a group of terrorists in a certain part of your body, let’s say in your urinary tract. To kill the terrorists, we can use a nuclear bomb. It will probably kill the terrorists but it will also cause a lot of collateral damage. In this example: the bad bacteria in the urinary tract, were the good guys in your bowels. Because we’ve nuked them and all other bacteria in your body, now you have diarrhea, leading to bad infections, and so on, and in the end, you may die. Sorry about that.

We’d rather use a sniper, a specific antibiotic, to kill the terrorist. To use a sniper, we need to know a couple of things.
1. Where are the bacteria hiding?
We need to choose an antibiotic that can shoot at the right place, at the right time. Not all snipers can go into every dark place of your body (no, not even there).

2. Which bacteria usually cause that particular kind of infection?
The bacteria causing of urinary tract infections are rarely the cause of pneumonia. So, these different bacteria need a different sniper, they need different antibiotics.

So, let’s continue with the example of the urinary tract infection. We need to establish first whether the terrorists are hiding in your left kidney (Middle East region) or your bladder (Western Europe). Then we need to culture your urine so we can see what bacteria is attacking us. This culture can take often five days, so we start a war using antibiotics based on the usual suspects (not a nuclear bomb but still a big bomb). As soon as we know the exact bacteria and what it’s susceptible for, we stop our bombing and bring in the sniper.

My name is Cillin, Penicillin

The James Bond of Antibiotic Warfare is Penicillin. Penicillin is probably the most snipery sniper, the top of all top-secret agents, if it was up to me I would call Penicillin Daniel Craig. It kills, when you need something killed, using his blue eyes and his perfect body…
It was born in 1928 (what …?) after a Scottish Microbiologist (oh, a history intermezzo) was conducting research on bacteria. He was doing this with the windows open and the fungus Penicillium, pretty common in nature, flew in. On the places where this fungus had landed, his bacteria didn’t grow. And so, Penicillin was discovered, still the corner stone of our antibiotics.

The scariest of bacteria, however, the bacteria that nowadays really kill you, are resistant to Penicillin. Even James Bond cannot save us. After 90 years, we still didn’t find a cure as effective as Penicillin.

Is the pharmaceutical industry not interested? Do we need to open our windows more and hope nature will solve our problem once more? Anyhow, something needs to happen: otherwise we will end up in an Antibiotic Resistance crisis.

Next time, Antibiotic Resistance crisis part 2, the BATTLE!

Antibiotic Resistance Crisis

Recently, a crisis of emerging antibiotic resistance gets more attention in the news. And it’s about time: the threat is more serious than diseases like swine flu or Ebola and could be deadlier than anything we’ve seen before (although, we have seen it before…).

Without antibiotics – or without the healing power of antibiotics – you, yes you, will die. Bam! Scary stuff, huh? Even the most common infections like pneumonia or urinary tract infections can not be treated without antibiotics, and you, yes you, will suffer.
Luckily, we still have antibiotics that work. But if we don’t use them properly, bacteria will learn how to defend themselves and will become resistant to all the drugs we have. 

We might get our crisis and experience life without them.

In the coming weeks I will post three articles on Antibiotics and the Resistance Crisis. In the first article I will explain the basics of Antibiotic warfare. The next will go into the details of the battle, in the third and last one is about the emerging crisis of antibiotics resistance. Have fun!

The Black Death

The Plague, aka the black death, aka bad news, is a disease most people only know from their history lessons and the Middle Ages. But it is also hitting the news right now. In Madagascar, last month 30 persons died of the plague, more than 200 are infected. With Dr Eric Bertherat, a WHO epidemiologist in our mind saying “You can become contaminated in the morning and be dead by the evening.” It makes you wonder: is history going to repeat itself?

Today, the plague can be avoided with the right hygienic measures and, if prevention fails, easily treated when diagnosed in time. In Madagascar both are lacking right now. The cause is probably the overcrowded and unhygienic prisons infested with rats and remote rural areas with rats that come out during rain season. And don’t think the prison walls can hold this infection inside. And definitely don’t think those straw-roofed houses can truly keep the rats outside.

So while the health care officials do all they can in Madagascar and try to solve it, let’s understand first what the deal is with this disease and why it is so infamous (by the way, don’t think the plague only shows up in remote African countries. Here is a map of affected regions in 2012).

The disease is transmitted through the bite of a flea from a rat. It can also be transmitted from human to human via contaminated fluids, tissue or droplets to fly through the air like kamikaze pilots. Although, the disease is scary, not to mention the fluids, fleas and rats, the plague is actually a “normal” bacterial infection, just like Chlamydia. It is caused by the bacterium Yersinia pestis, causing the bubonic plague and the plague of the lungs (90% mortality rate of that one). But wait, I hear you think, bacterium, the world has antibiotics to treat those!

Well, not in the late Middle Ages.

In those days, people dreaded the plague even more than people fear Simon Cowell’s verdict these days. Between 1347-1351, the plague was responsible for the death of nearly one third of the entire population of Europe. If this would happen today in Europe, you could drive from the Netherlands – where I was born – to Spain – where we would spend the occasional holiday – without ever seeing a living person. Well, I like to have some peace and quiet, but this was too much. It was the mother of epidemics.

Not only the rats and their fleas were to blame though.

The whole thing supposedly started with the Mongols (from the land Mongolia). They had used the disease to their advantage in 1346 when they wanted to invade the city of Kaffa (Ukraine). During the fight they would shoot the dead bodies of plague victims over the walls of the city using catapults, thus infecting the inhabitants. They must have been some real Angry Birds. The surviving inhabitants of Kaffa fled back to their daddies and mommies who still lived Italy. Through Italy the disease could spread further in Europe.

Venice had a fantastic plan to stop infections after the death of almost half the Venetians during the first half of the outbreak. They implemented the rule that all ships had to remain in the harbor without docking for 40 days. Probably from the 40 days of fasting from the bible. After those 40 days of quarantine, they could step on land.

Quick party conversation “fun”-fact: quarantine derives from the Italian word for 40 which is “quaranta”.

In the meanwhile, the medical school jumped to the opportunity to train the so-called plague doctors. These doctors didn’t wear the classical white coat, but they wore an ankle length black overcoat, black hat (quite stylish I must say) and a beaked mask. This beak was very smart to prevent infection (sure…) but also to eliminate the horrible smell coming from their patients. In the end of the beak they would put herbs and flowers to prevent them from gagging at their patient’s side, because that just isn’t professional.

So, the mask a lot of people wear during carnivals is actually a plague mask. Makes you look slightly different at the crowd, doesn’t it? Or what about the “Eyes Wide Shut” orgy scene? Maybe in 500 years a remake will be made with the future Tom Cruise and Nicole Kidman with the gear we wear today: white coats, chalked gloves and properly sealed mouth caps.

Strange world we will live in.

How an infection becomes an epidemic

After every disaster – man-made or natural – the news gets flooded with warnings about an eminent epidemic of infectious diseases, like for instance cholera. And in all fairness, it is indeed a serious risk. But how does that work?

Many infectious diseases are transmitted from person to person. Either directly by normal contact, sexual intercourse (in both a normal and abnormal way) or blood contact, or indirectly via a mosquito for instance. And this is completely different from all the other causes of illness.

For example:

• I can’t get diabetes because I had unprotected sex with someone with diabetes whom I just met in a bar after too many Jägerbombs (don’t judge me)
• The passengers in the bus can’t get kidney stones because someone sits too close to them, it’s just annoying if someone gets in your personal space

To get an infectious disease most of the time you have to actively do or actively not do something. In theory it should be easy to not get infected.

Actively do: if I have unprotected sex I am prone to get infected with all kinds of nasty stuff, so I should have made him wear a condom (I know, easier said than done, but still very effective).

Actively not do: if I stick the needle from someone else in my arm, I am bound to be infected with that person’s blood infections like HIV or hepatitis B (I … have … to … resist …)

Actively do and actively not do: if I don’t wash my hands (so please do) after I touch someone with diarrhea (please don’t, no really don’t), I am likely to infect myself and the persons I get in contact with afterwards.

Sounds simple to protect yourself, doesn’t it? Here’s the catch: in practice it is not always that easy and sometimes nearly impossible. Because what if you can’t get condoms? What if you need an immediate blood transfusion? Or if you don’t have fresh and safe water you can drink and wash your hands with? Let’s use this last example to make it clearer.

Lack of sanitation and fresh water is like throwing a big party for all infectious diseases to come and pick people to infect. You are reading this, so you probably have internet access and thus, most likely, access to clean water from a tap or other resources close by.

But don’t get too comfortable, if a hurricane occurs that destroys your supply, that flushes away your toilet and breaks open your sewer system letting all human waste flood the streets, you too will be in big trouble.

Cholera is one of the many diseases and always present in nature. With good hygiene, clean water, and a good health system it is not a big problem. But without it, cholera is the party animal. It starts with infecting just one or two people. They will soon get the typical heavy diarrhea that’s like pooping rice water all day long (not that I have any experience with it). They will dehydrate and they will die without care.

Unfortunately, this is not the end, cholera is just getting started.

Where is the diarrhea going when the sewer system to flush with it no longer exists? What happens with the buckets that are used to catch the diarrhea? How do you wash your hands after you’ve picked up that bucket? And what about the small children that have no idea what basic hygiene entails? That’s exactly what cholera likes. Easy access to a lot of people that basically have nowhere to hide. It will go from 1 person to 3, to 9, to 27 and so on and so on. Until an entire group that’s living closely together is infected, for instance in the emergency camp that has just been founded after a hurricane.

So, an epidemic is just moments away for all of us if we don’t have basic hygiene and knowledge of the infectious agents. And after a natural disaster it is hard to stay healthy and all the right support needs to be provided as fast as possible.

In all other cases, think about what you can actively do and actively should not do. Go wash your hands, use clean needles and please, don’t kiss a dead person when you don’t know what he or she died of (if not convinced, more about why not to do this will follow soon).

Do this and you’ll probably be fine, … for now.

 

Picture: Refugee camp for Rwandans in Kimbumba, eastern Zaire (current Democratic Republic of the Congo), following the Rwandan genocide.This image is a work of the Centers for Disease Control and Prevention, part of the United States Department of Health and Human Services, taken or made as part of an employee’s official duties. As a work of the U.S. federal government, the image is in the public domain.

Smallpox and the start of vaccinations

“Good old days”?! Not if you talk about infectious diseases. Being an infectious disease specialist before the last century would have been a dramatically frustrating profession. Even the simplest of infections could not be effectively treated.

In the 16th century there was an impressing global epidemic of smallpox, which is caused by the variola virus. This disease had been causing problems on and of for quite some time already and never failed to cause multiple deaths among the infected patients. The Inca population in South America was hit pretty bad in those days, the mortality among these people was 60-90%, and this was at the same time that the Spanish conquistadors were attacking them. So perhaps we could say that almost the entire continent of South America speaks Spanish not due to those Spanish horsemen, but in fact as a result of the variola virus.

The difficult situation with the smallpox is that the symptoms are very vague, some muscle aches, fatigue and fever. In this first stage of the disease patients are actually really contagious, so not recognizing the symptoms in time results in major problems and spread of the virus. After about 2 weeks the patient can get the classic skin leasions.

The only thing that the people in the 16th century could do to try to decrease the severity of the disease was a so called “inoculation with variola” (variolation). This meant that an attenuated virus was put on the skin in the hope that your body would start an immune response without actually killing you. In the work up for this “treatment”, children would be starved and about a liter of blood taken from them (don’t ask me why). After the variolation, the child would be locked in a barn until the disease had subsided or the child had died. Congrats for the ones that survived, I hope they had some good psychiatrists to regain their trust in humanity…

On a beautiful day in 1798 (don’t really know if it was, just sounds nicer), an English doctor called Edward Jenner was fed up with this torture of children. He too had undergone the variolation “treatment” and probably never got over the horror (again, total speculation). There had to be another way!

He noticed that the milkmaids of that time appeared to be immune to the smallpox. He thought that this might be due to the fact that they had probably been exposed to the, not so sickening, cow-pox. He decided to test this theory. He found a “volunteer” named James Phipps -the 8 years old son of his gardner- and injected him with the pus he had scraped from a cow-pock blister from a milkmaid. I mean, that just sounds like a brilliant idea, doesn’t it? Anyway, after some time he tried to infect the child with variola using the old “variolation” method but our little James didn’t get sick.

I can’t say that this was the most ethical way of investigating, but it was effective and had huge consequences for the world as we know it. Dr Jenner has written everything down in his book “An inquiry into the causes and effects of the Variolae vaccinae; a disease discovered in some of the Western Counties of England, particularly Gloucestershire, and known by the name of the cow pox”. Which is, like the title suggests, a real briefly written page turner…

From that day forward the procedure to prevent small pox would be to infect somebody with the cow-pox virus called “inoculation with vaccinia”, later “vaccination” after the word vacca that means cow in Latin. This particular vaccination could be terminated in 1980 when, thanks to intensive effort of the WHO, small pox was eradicated. OK, truth be told, it’s still present in 2 laboratories in Russia and the USA so maybe we should continue to take good care of our cows, just to be sure…