Zombie Genes, Slurpee Machines and Disease X

 

The story doesn’t always end after you kill a microbe. That death, in fact, can mark the beginning of a whole new life – for the organism’s genes.

According to MIT geneticist Eric Lander (below video), it works like this. Most bacteria carry, in addition to a regular set of chromosomes, an extra set of gene-carrying chromosomes called plasmids. And these genes often encode a protein that confers resistance to a range of antibiotics.

The reason for the presence of genes on plasmids is because plasmids are mobile, they move between living bacteria, conferring resistance along the way. But their movement isn’t confined to living bacteria: “It turns out that when bacteria die their cells crack open and their guts spill out – these little circles of DNA, these little plasmids.” At which point other bacteria will “slurp them up.”

Dr. Lander says this ability to slurp up zombie genes “is a little scary…. Because if we start using antibiotics willy-nilly, it’s pretty easy [to see] that if one species of bacteria had a … plasmid with a resistance gene, another species entirely can pick it up by horizontal transfer. [I]n fact, we are seeing an epidemic of antibiotic-resistant bacteria. Because as we use more antibiotics … [we’ve] selected for the bacteria that have picked up these things…. Not good, not good. And we’re seeing a huge spread of antibiotic resistance.“ (Emphasis added.)

This huge spread of drug-resistant microbes might be nearing critical mass. Last month, for example, the World Health Organization issued a list of disease-causing pathogens that have the potential to spread and kill worldwide and for which there are currently no, or insufficient, countermeasures available:

  • Crimean-Congo haemorrhagic fever (CCHF)
  • Ebola virus disease and Marburg virus disease
  • Lassa fever
  • Middle East respiratory syndrome coronavirus (MERS-CoV) and Severe Acute Respiratory Syndrome (SARS)
  • Nipah and henipaviral diseases
  • Rift Valley fever (RVF)
  • Zika
  • Disease X

The ominous sounding Disease X “represents the knowledge that a serious international epidemic could be caused by a pathogen currently unknown to cause human disease.” A “pathogen currently unknown” includes an existing microbe that, say, gains the ability to jump from animals to humans, for airborne transmission (imagine if HIV could do that), or mutates to become more virulent or more resistant to our drugs.

Experts in the field such as Dr. Michael Osterholm, founding director of the Infectious Disease Center for Research & Policy at the University of Minnesota, have been predicting a serious international epidemic, saying it’s not a question of if, but when. In his book Deadliest Enemy: Our War Against Killer Germs, Osterholm narrows the threat to antibiotic-resistant bacteria and the influenza virus, whose pathogenic potential relies in good part on their ability to mutate rapidly:

[T]here are only two microbial threats that … fit this description for pandemic potential. One is antimicrobial resistance and the very real threat of moving ever closer to a post-antibiotic era … a world more like that of our great-grandparents where deaths due to infectious diseases we now consider treatable are once again commonplace. The other is influenza, the one respiratory-transmitted infection that can spread around the world in short order and strike with lethal force.

 

One way microbes mutate rapidly is by the aforementioned plasma-mediated horizontal gene transfer. Here’s the engaging Eric Lander, former co-chair of President Obama’s Task Force on Combating Antibiotic-Resistant Bacteria, explaining to his first year MIT biology students how zombie genes and slurpee machines combine to yield Disease X potential. (The relevant bit runs from 2:40 – Why do cells have plasmids? – to 7:10.)

 

A severe flu can cause MRSA Pneumonia – but you can avoid all that

 

As the flu season mercifully winds down, a final lesson on the value of vaccination comes to us from Paul Auwaerter, MD, at the Johns Hopkins School of Medicine.

Having just finished a few weeks in the hospital doing infectious disease consultation, a number of the physician residents asked him why Staph aureus, and MRSA in particular, seem to have such a predilection for causing secondary bacterial pneumonia after a severe bout of the flu.

Citing recent research, Auwaerter thinks that severe influenza may disrupt the Staph/MRSA biofilm in the nasal passages: “About one third of people harbor S aureus in the nostrils, and dispersal from the biofilm in this setting may lead to aspiration of S aureus into the lungs, which might be more susceptible to infection.”

The remedy, he says, is prevention, i.e. the flu vaccine – but not just any old flu vaccine:

With this ferocious influenza season, it has become obvious that we need to do better with prevention. Specifically, influenza vaccines need to be reformulated every year, and this year, it was estimated that the flu vaccine effectiveness was only in the mid-30% range, although it was perhaps better among pediatric populations.

Many people, including both adults and children, don’t get immunized. There seems to be a genuine need, that I view as quite urgent, that more effort be given to developing a universal influenza vaccine – one that might be more durable and would cover most strains. This not only would lead to less influenza, hospitalizations, and deaths, but also would have a huge economic impact from less absenteeism from work or school, as well as the benefits to individual health.

On International Women’s Day Meet Canadian Scientist Julia Levy

 

VANCOUVER, CANADA  #IWD2018  #WomenInMicrobiology

Dr. Julia Levy’s research at the University of British Columbia in the 1980s led to the development of photodynamic therapy (PDT), initially for the treatment of cancer.

Julia Levy was born in Singapore. Her father was captured by the Japanese during WWll and put into a POW camp. Just before this, her mother had escaped to Vancouver with Julia and another daughter.

Inspired by her grade 11 biology teacher, a woman, Julia went on to obtain her BA in biology from the University of British Columbia, her PhD in experimental pathology from University College London, and after grauation became a professor of microbiology at UBC.

Together with her colleagues at UBC they developed photosensitive drugs which, upon being exposed to light, change in a way that makes them toxic to cells. The initial targets were cancer cells: cancers of the skin, lung, esophagus, stomach, bladder and cervix.

Dr. Levy also formed her own company, embarking on research that broadened the reach of PDT to treat other diseases such as skin infections, arthritis, psoriasis, multiple sclerosis, and – perhaps the most promising target – age-related macular degeneration. “It’s way beyond cancer,” Levy tells science.ca, excited about the potential to cure other diseases with this technology.

But here’s what’s most impressive about Dr. Levy – the impulse that led to her corporate success:

In 1986 she was giving a talk to some doctors in Waterloo, Ontario about her work on new light-activated drugs. The doctors were trying these drugs on cancer patients and they were very upset because Johnson & Johnson was closing down their drug development program which appeared to be effective against cancer. Many people were being helped by this technology, but soon they would not be able to get the drug. “It was a very upsetting experience for me,” says Levy, who until that point had worked on these drugs only in a laboratory. “For the first time, I became aware that we were talking about real patients being treated for real cancer.” And so right then and there Levy decided that “We’ve got to do something.” So she made a deal with J & J, raised $15 million, and took over the Canadian subsidiary. It was a major turning point for Levy and her company – and for cancer patients in Canada.

These days she lives a varied life. Some days are spent in meetings with other companies, others reading scientific literature, still others meeting her colleagues to work out business strategies. Levy likes everything about her work – except the travelling and talking to investors.

Looking back on it all, Dr. Levy is quick to credit the value of teamwork: “Well, when I look at it I think … me? And a lot of other people – you can’t do it alone.” And despite the wealth she has generated says, convincingly, “I’ve never found money to be a compelling reason to do anything.”

 

 

 

 

 

 

 

Antibiotic Therapy: Shorter = Better, Especially For Sicker Patients

A core issue in antibiotic therapy these past few years is duration; namely, should patients complete every dose of antibiotics prescribed, even after they feel better? The emerging consensus is no, and one of the leading proponents of this school of thought is the impeccably qualified Brad Spellberg, MD, Chief Medical Officer of the Los Angeles County-University of Southern California Medical Center, who says:

Every randomized clinical trial that has ever compared short-course therapy with longer-course therapy … has found that shorter-course therapies are just as effective.… Patients should be told that if they feel substantially better, with resolution of symptoms of infection, they should call the clinician to determine whether antibiotics can be stopped early. Clinicians should be receptive to this concept, and not fear customizing the duration of therapy.

That was in 2016 – and now we have an update. Just last week Dr. Spellberg added to the shorter is better mantra by saying that with sicker patients, those on 5-day courses of antibiotics have better treatment outcomes than those on 10-day courses. And that’s because the shorter duration group experience less antibiotic-driven superinfections, less drug resistance, and less antibiotic side effects.

The following are Dr. Spellberg’s remarks given at a webinar last week hosted by the Health Services Advisory Group in the United States. He addresses the antibiotic duration question beginning at the 41-minute mark. If you haven’t heard Spellberg in action, you want to. The written word cannot capture his passionate, sometimes sardonic, quick-witted way of speaking:

Since then, studies have come out on the sicker type of patients…. And the trials with the sicker patients found the same thing – not only are the antibiotics just as safe & effective [but] [t]here was one subpopulation in which there was a statistically significant difference found. That was the Port 4 & 5 population [people who should be hospitalized].

The sicker patient was the only population that found a difference in outcome between the short course therapy and the long course therapy group. And here’s the fascinating thing: The patients who were sicker did better with short course therapy. They actually had better clinical outcomes when they got 5 days than 10.

And so somebody commented to me at one point, Well that doesn’t make any sense. That would only be true if antibiotics were harmful. YEAH! That’s what it’s telling you. Antibiotics are harmful. They’re not this thing that magically cures disease and has no unfortunate side effects – that’s not real. Antibiotics have lots of problems associated with them: They breed out resistance. They breed out superinfections like C. diff [an antibiotic-driven bacterial infection] and Candida [a fungal infection]. They cause side effects.

Right? Who gets the resistance, the superinfections and the side effects? The sickest patients in the ICU. This makes perfect sense. Not only was there no improved outcome with longer therapy, patients who were sicker did better … with short course therapy.

Sneezing, as it turns out … is nothing to sneeze at

Range: 20 feet.

Speed: 25-50 mph.

Nature of the threat: “violent expirations” of tiny droplets from the nose or mouth of an individual that contain the flu virus.

With the cold and flu season still with us, NPR looked at the question of how the pathogens of one person become the pathogens of another. The answer, it seems, is that by getting us to cough or sneeze, these clever critters get free passage to a new “host” – us – and thus a new lease on life.

The other clever bit is that we’re tricked into thinking that if we feel okay then we’re not contagious. In truth, we’re contagious one day before we start feeling sick and up to seven days after we’re feeling better.

This matters because even beyond the harm the flu virus itself can do, it actually has a much longer reach. For instance:

It paves the way for secondary and deadly bacterial infections to set in, for example, MRSA, as happened with this woman.

It strains hospital resources breaking down infection control practices which can lead to superbug outbreaks as happened recently at this Ontario hospital.

And we commonly prescribe the wrong treatment for the flu – namely, an antibiotic – and suffer a severe side effect as a result. For example, the painful and often deadly C. difficile-caused diarrhea; irregular heartbeats and sudden death; tendon rupture; drug interactions causing people to end up in the emergency room; and the creation of drug-resistant bugs.

The CDC says there’s 3 ways to fight the flu: vaccinate, take an antiviral drug (these are not antibiotics), and “stop germs.” This engaging NPR video shows us that one important way to stop germs is to stay out of range of the sneeze.

 

A child’s illness and a parent’s fears

The main reason our antibiotics are becoming less effective is they’re being drastically overused in both medicine and food production. But cutting usage isn’t always simple. This video by British GPs nicely addresses one such complicating factor: a parent’s understandable desire to get their sick child well – but making a very common mistake in the process:

Understandably GPs will always get pressure especially from parents to prescribe antibiotics every day. And we know that your worst fear is your children getting ill and you want to protect them but trust us to know when you and your family will need antibiotics – you don’t need to ask for them.

Specifically, the physicians remind us, antibiotics don’t work on the cold and flu, and that sore throats, colds, coughs and earaches usually get better on their own, without antibiotics. Instead, they say, drink lots of fluids, rest, and eat at least one hot meal a day. And expect that a sore throat will usually last a week, and that a cold can last 10 days.

Say hello to your little valentine …

From Professor Sheena Cruickshank at the University of Manchester –

Oh what lovely eyes you have: With 38 trillion bacteria living in and on you and microbes such as Demodex caressing your face – it’s typically found in your eyelashes – you are never alone.

Happy valentines day.

 

 

Trade Wars – The superbug edition

The problem, say the Brits, is exactly as advertised: that the beef is US born & raised. And not just the beef, but the pork, chicken, and turkey, as well.

Britain’s beef bashing arose this week, The Guardian reports, as US trade reps in London are attempting to negotiate new contracts on food and agriculture in anticipation of Britain leaving the European Union.

As things stand, US meat is about as welcome over there as the flu virus. The EU already bans imports of American beef throughout the continent, mainly because of the free use of growth hormones in the US. And a row apparently broke out over the potential for imports of US chlorinated chicken, also banned by the EU. Bleaching chicken, according to UK experts, is a dangerous practice because it can serve to disguise poor hygiene practices in the food chain.

But the hot item is the overuse of antibiotics in food animals. The UK science-based NGO, Alliance to Save Our Antibiotics, is urging their government to stick to their guns and not import US meat because:

US cattle farmers are massively overusing antibiotics. This finding shows the huge advantages of British beef, which is often from grass-reared animals, whereas US cattle are usually finished in intensive feedlots. Trade negotiators who may be tempted to lift the ban on US beef should not only be considering the impact of growth hormones, but also of antibiotic resistance due to rampant antibiotic use.

 

It’s precisely this kind of farming that gives rise to superbugs such as MRSA – bacteria that antibiotics have zero effect on – that can kill or cause serious illness. This chart from the US Centers for Disease Control shows the relationship between farm and fork:

 

Notice something. By the time the meat arrives overseas, one of the two modes of transmission of the bugs from the farm to you has already been cut out – bugs moving through the environment, shown in the bottom half of the diagram. The Brits’ sole concern, therefore, is with the upper half of the diagram – meat that has been contaminated with the bugs (which are trickier to get rid of than you’d think). In other words, the Brits are unwilling to be exposed to even half the risk of infection from these bugs that Americans are forced to live with.

And what is Washington’s reasoned response to the health concerns raised by the UK? Ted McKinney, US under-secretary for trade and foreign agricultural affairs, told an audience of British farmers last month he was “sick and tired” of hearing British concerns about chlorinated chicken and US food standards.

 

 

 

 

They were supposed to save his life not take it

We know that hospital-acquired infections in Canada kill 8,000 to 12,000 people every year and may well be the 4th leading cause of death in the country. Yet we hear very little about that and even less about how those deaths occur.

However, the compelling story of George Gould (below), who caught an untreatable superbug infection at the Vancouver General Hospital is an exception. His wife went public because of his prolonged suffering that involved some 22 hospitalizations over 18 months. And she went public because, in her words, the hospital was “supposed to save his life not take it.”

We understand her anger. But as the high number of infection-related deaths suggest, the problem doesn’t lie with any one hospital; rather, it’s a systemic issue – and so we all have to be on guard.

Brad Spellberg, MD, Chief Medical Officer at the Los Angeles County-University of Southern California Medical Center, tells us why hospitals are such dangerous places:

I do think that people need to understand that the hospital is an inherently dangerous place and it’s not because hospitals are dirty or doctors are lazy or anything like that. Think about it this way. You’re taking the sickest people in society, crowding them into one building, tearing new holes in their bodies that they didn’t use to have by placing plastic catheters in their bloodstream, their bladder, putting tubes into their lungs that can breathe for them, and we’re using very large quantities of antibiotics to treat infections. So that’s a perfect breeding ground to generate antibiotic resistant bacteria.

 

Armed with this knowledge, is there anything we can do to protect ourselves? Andrew Simor, MD, an infectious disesae specialist with the Sunnybrook Hospital in Toronto, says we need to be more assertive:

I think patients need to advocate for themselves to ensure that there are proper infection prevention control standards in place. That hand hygiene is being done consistently as it should be. And that other barrier precautions [such as] use of gowns and gloves environmental cleaning is being done as it should be. I think we all need to advocate for ourselves and for our patients to ensure that this is happening.

 

The flu vaccine can protect you from MRSA and other deadly pathogens

 

U.S. influenza activity is now the most widespread since the 2009 influenza pandemic, according to the Centers for Disease Control and Prevention in its latest weekly update on flu activity. The CDC therefore urges Americans to get a flu vaccine if they haven’t already because “There is still a lot of the season to go, and vaccination now could still have some benefit.” That doesn’t guarantee that you’ll be 100 per cent protected from the flu, however, “Even if you get the flu, having received the flu vaccine may help you in terms of not having as serious a course or as devastating a course.” And that, as it turns, can matter a lot.

Tandy Harmon (above), 36, a single working mother of 11- and 12-year old boys from Portland, Oregon, was in good health until she starting feeling ill with the flu one Sunday earlier this month. The next day, she stayed home from her job as a bartender at a local sports lounge. By that Wednesday, she ended up in intensive care at Legacy Emanuel Medical Center in North Portland, diagnosed with the flu, pneumonia and an infection from Methicillin-resistant Staphylococcus aureus (MRSA).

Harmon’s symptoms became severe fast. Her organs started to shut down. Her liver failed. Her skin started to discolor. They even considered the amputation of limbs as an option to keep her alive. And two days later, after a decision was made to remove her from life support, she died, leaving family and friends stunned. “That’s all it took was a couple of days,” said her boyfriend Steven Lundin. “I can’t believe it.”

Dr. John Townes, head of the infectious disease program at Oregon Health & Science University explained what happened in an interview with The Oregonian:

[T]hey get the flu. That opens the floodgates for the bacteria to invade their body. This happens every year. This is why we harp about getting a flu vaccine. The flu can lead to severe bacterial infection. The usual average healthy person doesn’t die of influenza [but] influenza will lower your resistance to certain bacterial infections like staph infection or pneumococcal infection.

People at high risk for the flu – and thus should be vaccinated – are children younger than age 5 but especially less than age 2, adults age 65 and over, pregnant women, and people with underlying medical conditions such as lung disease, heart disease and diabetes.

Townes says you probably have the flu if you feel “sick all over.” In which case you should stay home, rest and stay away from others.

But what you really need to watch out for, he says, is if you start to feel better and then get worse. That’s when you should see a doctor because it’s a sign of something serious: that a bacterial infection such as MRSA has set in secondary to the viral infection – as was the case with Tandy Harmon.

 

 

 

 

 

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