“Human resistance to antibiotics could bring ‘the end of modern medicine as we know it’,” according to The Daily Telegraph. The newspaper says that we are facing an antibiotic crisis that could make routine operations impossible and a scratched knee potentially fatal. Similarly, the Daily Mail’s headline stated that a sore throat could soon become fatal.
The alarming headlines follow a new report by the World Health Organization (WHO , which set out ways to fight the growing problem of antimicrobial resistance (AMR . AMR occurs when infectious organisms, such as bacteria and viruses, adapt to treatments and become resistant to them. The publication specifically addressed the long-known problem of antibiotic resistance, where increasing use of antibiotics can lead to the formation of “superbugs” that resist many of the antibiotic types we currently have. It outlined a variety of measures that are vital for ensuring we can still fight infections in the future and described how other major infectious diseases, such as tuberculosis, HIV, malaria and influenza, could one day become resistant to today’s treatment options.
However, despite the future danger posed by antimicrobial resistance, the situation is not irretrievable. As Dr Margaret Chan, director general of WHO, said: “much can be done. This includes prescribing antibiotics appropriately and only when needed, following treatment correctly, restricting the use of antibiotics in food production to therapeutic purposes and tackling the problem of substandard and counterfeit medicines.” The report also highlighted successful cases where antimicrobial resistance has been tackled, demonstrating that we can safeguard the effectiveness of important antimicrobial medicines with dedicated, rational efforts.
Where has the news come from?
WHO has just published a new report (“The evolving threat of antimicrobial resistance - Options for action” that sets out a global strategy for fighting antibiotic resistance. It explores how over past decades, bacteria that cause common infections have gradually developed resistance to each new antibiotic developed, and how AMR has evolved to become a worldwide health threat. In particular, the report highlights that there is currently a lack of new antibiotics in development and outlines some of the measures needed to prevent a potential global crisis in healthcare.
This is not the first time WHO has set out such a strategy. In the 2001, WHO published its “Global strategy for containment of antimicrobial resistance”, which laid out a comprehensive list of recommendations for combating AMR. The current report looks at the experiences over the past decade of implementing some of these recommendations, the progress made, and what else should be done to tackle AMR.
What is antimicrobial resistance?
Antimicrobial resistance (AMR occurs when microorganisms, such as bacteria, viruses, fungi or other microbes, develop resistance to the drug that is being used to treat them. This means that the treatment no longer effectively kills or inactivates the microorganism. The term “antimicrobial” is used to describe all drugs that treat infections caused by microorganisms. Antibiotics are effective against bacteria only, antivirals against viruses only, and antifungals against fungi.
The case of penicillin illustrates the AMR phenomenon well. When penicillin was first introduced in the 1940s, it revolutionised medicine and was effective against a wide range of staphylococcal and streptococcal bacteria. It was also able to treat infections that had previously been fatal for many people, including throat infections, pneumonia and wound infections. However, with increasing use of antibiotics over the decades, bacteria began to adapt and develop changes in their DNA that meant they were resistant to the actions of the once-powerful antibiotic. These bacteria would survive and proliferate, which meant their protective genes would then be passed on to other strains of bacteria. As a result, new and stronger antibiotics had to be created to combat the resistant bacteria.
AMR is driven by many factors, including overuse of antimicrobials for human and animal health and in food production, which can allow microbes to adapt to antimicrobials they are exposed to. Poor infection-control measures, which fail to prevent the spread of infections, also contribute. In particular, the WHO publication reports what it describes as the five most important areas for the control of AMR, as recognised in its 2001 strategy:
- surveillance of antimicrobial use
- rational use in humans
- rational use in animals
- infection prevention and control
- innovations in practice and new antimicrobials
How big is the problem?
As the report describes, AMR makes it difficult and more expensive to treat many common infections, causing delays in effective treatment or, in the worst cases, an inability to provide effective treatment at all. Many patients around the world suffer harm because infections from bacteria, viruses, fungi or other organisms can no longer be treated with the common medicines that would once have treated them effectively.
The report presents some startling facts on major infectious diseases worldwide:
- Malaria: malaria is caused by parasites that are transmitted into the blood stream by a bite from an infected mosquito. Resistance to antimalarial medicines has been documented for all classes of the drug, which presents a major threat to malaria control. The report describes that a change in national antimalarial treatment policy is recommended when the overall treatment failure rate exceeds 10%. Changes in policy have been necessary in many countries due to the emergence of chloroquine resistance. This means that alternative forms of combination therapy have to be used as first-line treatment.
- Tuberculosis: in 2010, an estimated 290,000 new multidrug-resistant tuberculosis (TB cases were detected among the TB cases notified worldwide, and about one-third of these patients may die annually. Inaccuracies in diagnosis also impede appropriate treatment.
- HIV: resistance rates to anti-HIV drug regimens ranging from 10% to 20% have been reported in Europe and the USA. Second-line treatments are generally effective in patients when the first-line therapy has failed, but can only be started promptly if viral monitoring is routinely available.
- Common bacterial infections: various bacteria can cause infections within the chest, skin and urinary tract bloodstream, for example, and the inability to fight these infections appears to a growing problem in healthcare. Estimates from Europe are that there are 25,000 excess deaths each year due to resistant bacterial hospital infections, and approximately 2.5 million avoidable days in hospital caused by AMR. In addition, the economic burden from additional patient illness and death is estimated to be at least ˆ1.5 billion each year in healthcare costs and productivity losses.
What can be done about AMR?
The five key areas that the report highlights could tackle the problem of AMR are as follows:
Surveillance of antimicrobial use
Tracking antimicrobial use (in particular antibiotic use and looking at the emergence and spread of resistant strains of bacteria is a key tactic in the fight against AMR. This can provide information, insights and tools needed to guide policy and measure how successful changes in prescribing may be. This can happen both locally and globally.
AMR is a global problem but, at present, there appears to be wide variation in the way regions and countries approach AMR surveillance. This means there is a long way to go before it can be carried out worldwide.
Rational use in humans
Antimicrobials can obviously be important or even lifesaving in appropriate situations, but it is just as important to prevent unnecessary use of antimicrobials, which can lead to resistance. Putting this into practice worldwide is said to be difficult, but rationalising antimicrobial use has had a demonstrable impact on AMR in some cases.
Rational use in animals
Antibiotics are said to be used in greater quantities in food production than in the treatment of disease in human patients. Also, some of the same antibiotics or classes are used in animals and in human medicine. This carries the risk of the emergence and spread of resistant bacteria, including those capable of causing infections in both animals and people.
The problems associated with the use of antibiotics in animal husbandry, including in livestock, poultry and fish farming, are reportedly growing worldwide without clear evidence of the need for or benefit from it. There are said to be major differences in the amounts of antimicrobials used per kilogram of meat produced in high-income countries, and actions need to be taken by national and international authorities to control this.
Infection prevention and control in healthcare facilities
The hospital environment favours the emergence and spread of resistant bacteria. The report highlights the importance of infection-control measures to prevent the spread of microbes in general, regardless of whether they are resistant to antimicrobials. Many facilities and countries are reported to have progressed well since 2001, implementing many recommendations on infection control and prevention, although gaps and challenges still remain.
Innovations
Lastly, the report describes how innovative strategies and technologies are needed to address the lack of new antimicrobials being produced. As the report says, while antimicrobials are the mainstay of treatment for infections, diagnostics and vaccines play important complementary roles by promoting rational use of such medicines and preventing infections that would require antimicrobial treatment. So far, new products coming on to the market have not kept pace with the increasing needs for improvements in antimicrobial treatment. However, current challenges to new research developments can be both scientific and financial.
Can these strategies really stop AMR?
While AMR poses a significant threat to health in the future, the situation does not appear to be irretrievable. The WHO report and an accompanying press release highlight some examples of success stories over the past years:
- In Thailand, the "Antibiotic Smart Use" programme is reported to have reduced both the prescribing of antibiotics by prescribers and the demand for them by patients. It demonstrated an 18–46% decrease in antibiotic use, while 97% of targeted patients were reported to have recovered or improved regardless of whether they had taken antibiotics.
- A pharmacy programme in Vietnam reportedly consisted of inspection of prescription-only drugs, education on pharmacy treatment guidelines and group meetings of pharmacy staff. These measures were reported to give significant reduction in antibiotic dispensing for acute respiratory infections.
- In Norway, the introduction of effective vaccines in farmed salmon and trout, together with improved fish health management, was reported to have reduced the annual use of antimicrobials in farmed fish by 98% between 1987 and 2004.
- In 2010, the University of Zambia School of Medicine was reported to have revised its undergraduate medical curriculum. AMR and rational use of medicines were made key new topics to ensure that graduates who enter clinical practice have the right skills and attitudes to be both effective practitioners and take a role in fighting AMR.
How can I do my part?
There are times when antibiotics are necessary or even vital. However, as patients and consumers, it is important to remember that antibiotics or other antimicrobials are not always needed to treat our illnesses, and we should not expect them in every situation.
For example, the common cold is caused by a virus, which means it does not respond to antibiotics. However, people may expect to be given antibiotics by their doctor when they are affected, even though they offer no direct benefit and could raise the risk of bacteria becoming resistant. Furthermore many common viral and bacterial infections such as coughs, throat and ear infections and stomach upsets, are “self-limiting” in healthy people, which means they will generally get better with no treatment at all.
If, on the other hand, you are prescribed an antimicrobial, it is important to take the full course as directed. Taking only a partial course of an antimicrobial may not kill the organism but may expose it to a low dose of a drug which can then contribute to resistance.
Links To The Headlines
Health chief warns: age of safe medicine is ending. The Independent, March 16 2012
Human resistance to antibiotics could bring "the end of modern medicine as we know it", WHO claim. The Daily Telegraph, March 16 2012
Why a sore throat could soon be fatal: Bugs are becoming more resistant to antibiotics, warn health chiefs. Daily Mail, March 16 2012
Links To Science
WHO: The evolving threat of antimicrobial resistance - Options for action. March 16 2012
writes:
The statistics are stark. More than 1 in 3 Native American women will be sexually assaulted their lifetimes, a rate much higher than the general population. In one study, a stunning 92% of young women reported they had been forced to have sex against their will on a date.
One of the primary fears of any rape victim is an unintended pregnancy. The first line of defense against that possibility is, of course, the prompt administration of emergency contraception.
And this is where things get tricky for many Native women. Most receive their health care from the Indian Health Service and affiliated tribal health centers. Of 157 IHS facilities, only 10% surveyed stock Plan B in their pharmacies, and only 37.5% carried some alternative form of emergency contraception. In the Albuquerque Area, which covers almost all of New Mexico and Utah, only two of its 15 facilities stocked Plan B.
"If you are living on the reservation or on the Pueblos without insurance, or the money to pay for EC or transportation to get you to town, you are out of luck, because you do not have accessibility through our own health care provider," says Charon Asetoyer, a Comanche from Lake Andes, South Dakota and Executive Director of [the Native American Women's Health Education Resource Center].
And that assumes women even know to ask or find it. "A lot of women in our communities aren't aware that Plan B even exists or they associate it with the abortion pill RU486, they don't realize the difference because the media and the opposition have projected this: it's an abortion pill, when it really is a contraceptive," Asetoyer notes. [...]
The so-called “conscience clause” also comes into play. "We have had rape victims given prescriptions to get EC, but at IHS they wouldn't administer it, because the Pharmacy Director and her staff didn't believe in it, so she wouldn't administer EC," says Lisa Thompson-Heth of the Lower Brule Sioux Tribe in Fort Thompson, South Dakota. [...]
"It's not an aspirin; it's not cold tablets,” says Asetoyer. “It's withholding services from a victim.”
Blast from the Past. At Daily Kos on this date in 2010:
You may have already taken note of the gay-hating, immigrant-bashing, ignorance-promoting, climate change-denying, anti-choice, scofflaw attorney general of Virginia, Ken Cuccinelli II. Well, here's another of his finest moments. [...]
Question: What can we do about Obama and the birth certificate thing?
Cuccinelli: It will get tested in my view when someone... when he signs a law, and someone is convicted of violating it and one of their defenses will be it is not a law because someone qualified to be President didn’t sign it.
Q: Is that something you can do as Attorney General? Can you do that or something?
Cuccinelli: Well, only if there is a conflict where we are suing the federal government for a law they’ve passed. So it’s possible.
Q: Because we are talking about the possibility that he was not born in America.
Cuccinelli: Right. But at the same time under Rule 11, Federal Rule 11, we gotta have proof of it.
Q: How can we get proof?
Cuccinelli: Well... that’s a good question. Not one I’ve thought a lot about because it hasn’t been part of my campaign. Someone is going to have to come forward with nailed down testimony that he was born in place B, wherever that is. You know, the speculation is Kenya. And that doesn’t seem beyond the realm of possibility.
Hey, CNN, you can't say that Blagojevich's 15 minutes are up while you're simultaneously covering him.—
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The Daily Mail today put a dampener on the approaching Mother's Day by telling us that it is our mum’s fault if we are “losing the fight against the flab”. The newspaper said that a new study has shown that our mother’s lifestyle may leave us “programmed to be fat”.
Thankfully for our relationships with our mums, the research does not actually say this. The study in question aimed to investigate whether DNA modifications in early life are linked to our size and body composition in later childhood. The modification in question does not change the underlying genetic code but it does decreases the amount of proteins the body makes using the instructions in our genes.
After stringent testing the researchers found only one significant link, between the modification of one gene and height rather than weight. None of the links between DNA modification and body mass index (BMI stood up to stringent testing, and even the study’s authors note the study cannot prove that the DNA modification at birth definitely directly affected height. For the time being, it is probably best to work on improving our health by addressing the lifestyle factors that we can change.
Where did the story come from?
The study was carried out by researchers from Newcastle University and other research centres in the UK. It was funded by the Biotechnology and Biological Sciences Research Council, Special Trustees of Newcastle Hospitals, the UK Medical Research Council, the Wellcome Trust, the University of Bristol, Asthma UK, the medical nutrition firm Nutricia UK, and the pharmaceutical company Novo Nordisk.
The study was published in the peer-reviewed open access scientific journal PLoS One.
The story was covered by articles from the BBC News and the Daily Mail, which both featured headlines focusing on how factors in the womb might influence obesity. However, the study found only one outcome to be statistically significant – a link with height.
The BBC did state that only one link stood up to rigorous testing but did not say this was a link with height rather than BMI or body fat levels.
The study did not look at obesity itself, rather it looked at BMI and fat mass. It did not classify the children into weight categories such as ‘overweight’ or ‘obese’ in its analyses, nor did it look at ability to lose weight, as suggested by the Daily Mail’s headline about ‘losing the fight against the flab’.
Both sources mention factors that might influence these DNA modifications in the womb, such as diet, exercise, smoking or drinking alcohol. However, it is important to note that the study did not look at why the DNA modifications might have occurred, so they cannot be attributed to these or any other factors based on this study.
What kind of research was this?
The body uses DNA as the blueprint for producing a range of important proteins. Sections of DNA produce individual proteins are known as genes.
In this study, researchers looked at a type of DNA modification called ‘methylation’, where a chemical compound called a methyl group becomes attached to the outside edge of a DNA strand. This process does not change the underlying genetic code, but it does reduce the amount of protein the body produces using nearby genes. It is one of the ways the body can control how much of each protein is produced.
The study looked at whether the levels of DNA methylation shortly after birth had any relationship to body size later in childhood. To examine the issue it analysed information collected in two cohort studies: the Preterm Birth Growth Study (PBGS , and the Avon Longitudinal Study of Parents and Children (ALSPAC . The level of methylation after birth was calculated using analyses of umbilical cord blood.
What did the research involve?
The researchers initially wanted to identify which genes might be related to BMI composition in childhood. To do this they looked at a group of 24 children in the PBGS study whose BMIs had been measured when they were aged between 11 and 13 years (average 12.35 years . They then looked at how active various genes were in the children with the highest BMIs and those with the lowest BMIs. They did this to identify genes that could be affecting BMI, to target these genes for investigation in the next phase of the study.
A selection of the genes identified through this first phase of the study were then assessed in a second phase of the study, to see whether these differences in gene activity in later childhood, and changes in BMI, might be related to the level of DNA methylation that was in place from the time of birth. The genes selected for this second phase were selected because they could be assessed with the technology the lab had available.
In this second part of the study the researchers looked at the levels of DNA methylation in blood collected from the umbilical cord of 178 babies taking part in the ALSPAC study. These babies had been followed up through childhood, and had data on their body composition, including BMI, fat mass, lean mass, and height at about age nine (average age 9.8 years . Methylation was measured in up to three places within the selected genes.
The researchers analysed whether the level of methylation of these genes at birth was related to body composition at age nine.
What were the basic results?
In the first part of their study, looking at children aged about 12 years, the researchers found that 514 genes had different levels of activity in those with higher BMIs and lower BMIs. From the genes they identified they selected 29 of these genes to look at in the second part of their study.
They found that four of these 29 genes were not methylated in the 178 cord blood samples tested, so they did not study these genes any further. The methylation levels of nine of the remaining genes were each related to at least one measure of body composition at age nine.
However, once the researchers took into account the number of statistical tests they had performed, the methylation level of only one gene was found to have a statistically significant association with a body composition measure. The gene in question was called ALPL, and higher levels of methylation of this gene in umbilical cord blood at birth were associated with being shorter at age nine. Each 1% increase in DNA methylation of ALPL was linked with a 0.15% decrease in height at age nine.
How did the researchers interpret the results?
The researchers conclude that the patterns of DNA methylation in cord blood showed some association with body size and composition in childhood. However, they note that their study is not able to say whether the changes in DNA methylation seen actually cause the differences in body size and composition in childhood, and further research is needed to investigate this.
Conclusion
In recent years there has been a lot of scientific and public interest in how events early in the womb may relate to our health in later life. In this vein, the national press have picked up on this study, which investigated whether DNA modifications during early life might impact on body size and composition in later childhood.
While these press narratives have given the impression that this study linked particular environmental exposures in the womb such as maternal smoking and drinking can lead to DNA modifications and later obesity, this is not the case:
- The news sources mention factors that might influence these DNA modifications in the womb, such as the mother’s diet, exercise, smoking, or drinking alcohol. However, it is important to note that the study did not look at how or why the DNA modifications might have occurred, so they cannot be attributed to these or any other factors based on this study.
- The study did not look at obesity, rather it looked at BMI and fat mass. It did not classify the children into weight categories such as ‘overweight’ or ‘obese’ in its analyses. It also did not look at whether participants had difficulty losing weight, as suggested by the Daily Mail’s headline about why some people may be ‘losing the fight against the flab’.
- The study was relatively small, and only looked at methylation of a small number of genes. Only one association between methylation of one gene at birth and height remained statistically significant after stringent testing. However, the authors themselves note that their study cannot prove that the DNA methylation pattern at birth caused the differences in height seen.
- None of the links between DNA methylation at birth and BMI or fat mass remained statistically significant in stringent tests. This means that they cannot be said to be real associations, as they may therefore have just occurred by chance.
If the results of the current study can be confirmed in other studies, researchers will need to try and work out if the link is causal. Even if the link is confirmed and found to be causal (and it is a big IF , it is not clear what, if anything, could be done to alter this.
For the time being, we are probably best working on improving our health by addressing the factors that we know we can change, rather than blaming our Mums for making us ‘programmed to be fat while in the womb’. Not a nice sentiment in the run-up to Mother’s day.
Analysis by Bazian
Links To The Headlines
Study links womb environment to childhood obesity. BBC News, March 15 2012
Losing the fight against the flab? It's your mum's fault! Research shows we are programmed to be fat while in the womb. Daily Mail, March 15 2012
Links To Science
Relton CL, Groom A, St. Pourcain B et al. DNA Methylation Patterns in Cord Blood DNA and Body Size in Childhood. PLoS ONE, 2012 7(3 : e31821
But our enemies give us no choice. Presidential candidates, congresspeople, state legislators and assorted censorious private-sector busybodies empowered by the
Vatican or Rush Limbaugh or their own twisted view that everybody should be beholden to their assessment of what's right for every woman to do with her own body have ramped up their crusade in the past couple of years. What had been a steady nibbling away at women's legal right to abortion has become a full-blown assault that has spilled over into promoting controls on who can use contraception and for what purpose.
We can discuss all day long the origins and hypocritical, double-standard, patriarchal and parochial underpinnings of those who are carrying out this assault. But that takes time away from putting a stop to it, from fighting it head-on and from moving from self-defense to offense. Besides making things tougher to pass the worst such laws, as happened with Virginia's transvaginal ultrasound bill, turning the tables on these benighted reactionaries is what liberals/progressives/leftists ought to be doing.
In the battles we've had pushing back against these reactionary attacks, some hard-to-ignore allies have joined us. They oppose what we oppose and/or support what we support and we can make gains by getting others to do likewise. For instance, the Pennsylvania Medical Society, as Joan McCarter
points out in her diary, opposes requiring ultrasounds before abortions.
You can sign a petition asking the American Medical Association to add their opposition to forced ultrasounds here.
Self-defense is essential. But the goal of merely hanging onto what we've got when what we've got includes the Hyde Act that punishes poor women and religious conscience laws that permit pharmacists to refuse to fill prescriptions for women who have been raped is simply not enough. That self-defense battle must continue, of course. Not least because the forced-birthers are always coming up with new attacks, like personhood laws that make fertilized eggs equal to human beings already born.
(Continue reading below the fold
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