Antibiotic resistance poses threat to MDG progress

 This piece is by Ramanan Laxminarayan, who has worked with the World Health Organization (WHO) and the World Bank on disease control and policy evaluation and is currently the director of the Center for Disease Dynamics, Economics & Policy.

The year 2015 marks the target date for completion of the eight United Nations Millennium Development Goals (MDGs), a set of objectives laid out by world leaders in 2000 with the aim of, among other things, improving global health and preventing the spread of infectious diseases. Great strides have been made in combatting “HIV/AIDS, malaria and other diseases” (MDG 6). According to the UN’s 2013 progress report on the MDGs, several of the objectives laid out for fighting infectious diseases have been reached. The MDG target of halting and beginning to reverse the spread of HIV, for instance, has been met, and access to HIV treatment has been dramatically expanded. The death rate from tuberculosis decreased 41 percent in 20 years, and global malaria deaths were reduced by 26 percent between 2000 and 2010. We have also taken significant steps toward achieving the targets laid out in MDG 4 by reducing child deaths, which are commonly caused by diseases like pneumonia and malaria. Indeed, the under-five mortality rate decreased by 47 percent between 1990 and 2013.

Our progress in fighting infectious diseases and saving lives, however, could grind to a halt – or even be reversed – if we do not address the increasingly pressing issue of antimicrobial resistance (AMR). In its first global report on AMR, released in early May, the World Health Organization (WHO) warned that high rates of resistance have been observed around the world in bacteria that cause common illnesses, such as urinary tract infections, pneumonia, gonorrhea, and staph infections. As WHO Assistant Director-General for Health Security Keiji Fukuda points out in the report’s foreword, “a post-antibiotic era – in which common infections and minor injuries can kill – far from being an apocalyptic fantasy, is instead a very real possibility for the 21st century.”

  • While the MDG progress reports have shown decreasing HIV infection rates and increased access to treatment, the World Health Organization has reported higher transmission rates of antiretroviral-resistant strains of HIV. It is estimated that between 10 and 17 percent of patients without prior antiretroviral treatment in Australia, Europe, Japan, and the United States are infected with an HIV strain that is resistant to at least one antiretroviral drug.
  • The re-emergence of malaria in countries like Venezuela, which were considered free of the disease for decades, shows that proper surveillance and prevention are lacking in many parts of the world. Adding to the problem are artemisinin-resistant strains of malaria, which have been identified in five countries in Southeast Asia and pose a risk to other countries in the region.
  • Multidrug-resistant tuberculosis (MDR-TB) is also becoming ever more common. There were approximately 450,000 new cases of MDR-TB in the world in 2012, more than half of which occurred in China, India, and Russia. In many countries, more severe strains of extensively drug-resistant TB (XDR-TB) are increasingly prevalent.

These numbers paint a worrying picture: If left unchecked, antimicrobial resistance could mean the undoing of all the progress made under the MDGs. The Sustainable Development Goals (SDGs), which are part of the UN’s post-2015 development agenda, must emphasize antimicrobial resistance as a threat to global health that must be overcome.

Improving surveillance of antimicrobial consumption and resistance is one of the most important steps in this process. The WHO report threw into sharp relief the inconsistent, underdeveloped surveillance techniques that are used in much of the world. In order to better fight AMR, we must reach a global consensus on the standards used to track resistance indicators. This will require the establishment of national databases to track antibiotic sales, consumption, and bacterial resistance profiles. It will also require collaboration between nations. Efforts such as the European Antimicrobial Resistance Surveillance Network (EARS-Net) and the Center for Disease Dynamics, Economics & Policy’s Global Antibiotic Resistance Partnership, which seeks to establish actionable policy proposals on antibiotic resistance in low- and middle-income countries, are already underway – but more such initiatives will be necessary.

Doctors, patients, and pharmacists must also be educated on proper prescribing practices and use of antimicrobials. In many countries, antibiotics are sold in pharmacies without a prescription, and even in countries like the United States, where over-the-counter laws are strict, it is estimated that half of antibiotic prescriptions are unnecessary. The indiscriminate prescribing and consumption of these drugs are contributing to the rising rates of resistant bacteria in both community and health-care settings.

The situation is further complicated by the dwindling supply of effective drugs. Overcoming this obstacle will require a multipronged approach that pushes for investment into research and development efforts, as well as the removal of bureaucratic barriers that often stand in the way of the approval of new pharmaceuticals.

Ensuring that there is a concerted international effort to address these problems will undoubtedly present a challenge for the global health community. With the MDGs in their final stages, governments around the world must come together to set new goals that ensure the gains we have made since 2000 are not lost to the threat of drug-resistant bacteria.


An Epidemic of Epidemics

Turning points in history can be identified with certainty only with the benefit of hindsight. The signs are, however, that [we are] at a key moment in the history of mankind’s struggle against infectious diseases
Lancet Infectious Diseases, Editorial

This year saw the sad passing of the leading medical anthropologist and historian, George Armelagos. In a widely cited 1996 paper, Armelagos argued that the emergence and resurgence of disease was the result of the interaction of some or all of the following factors:

  • global social, demographic, and environmental changes
  • international trade, travel and technological change
  • breakdown of public health measures
  • the adaptations and genetics of microbes

The relevance of this framing to current patterns of diseases becomes clear when we look at current examples of infectious disease threats. Consider the following four stories, all drawn from the last two weeks:

  • The Centre for Disease Control announce that US measles cases are at a 20 year high, with outbreaks occurring among unvaccinated clusters of people exposed to travellers bringing the measles virus back from other countries – most notably the Philippines, where a large outbreak began in October 2013.
  • The World Health Organization confirms that the Ebola outbreak in West Africa has reached Sierra Leone, and that control of the disease – which has no known vaccine or cure and is suspected to originate from bats and transferred to humans through bushmeat production processes – is inadequate to the scale of the problem.
  • The UAE government revises upwards its estimates from deaths related to MERS – the Middle Eastern variant of SARS, which recently reached European and American shores  - while researchers find evidence that the MERS virus is identical to one that also kills camels, and worrying reports emerge about the proximity of MERS incidence sites in Saudi Arabia with the hajj routes for 4 million pilgrims travelling to Mecca.
  • The UK Chief Medical Officer, Dame Sally Davies held a briefing at the Royal Society in which she provided data showing that 5,000 deaths a year in the UK, and over 25,000 across Europe, were due to drug-resistant diseases. In America, the mortality figures for hospital-acquired infections alone top 99,000.

These stories usefully illustrate the different ways in which the drivers described by Armelagos have combined to raise disease incidence and impacts around the world. Of course, disease is far from being the only outcome of these drivers. We live in an era of unrivalled human influence on the planet – what some have called the ‘anthropocene’. The UN has described the physical and ecological changes wrought by globalisation as ‘the most fundamental transformation triggered by human civilisation since rise of agriculture’.

It is perhaps no coincidence, then, that in subsequent studies Armelagos compared our modern disease landscape to precisely the one humanity faced ten millennia ago, when we started moving away from hunter-gatherer lifestyles and toward more settled lives. The agricultural revolution, like the current global revolution, saw humans radically change their environment. We started to live in more continuous contact with animals, and with each other. From this period, we began to be afflicted by many major diseases that are still prevalent in developing countries today: measles, small pox, influenza, mumps, cholera – the list goes on.

Starting in the 19th century and continuing through much of the 20th, it seemed as though we were gaining the upper hand over the assembled legions of our microbial enemies.Thanks to modern medical advances, disease was being conquered, or at the very least, firmly controlled. We had antibiotics to treat bacterial infections, vector control programmes to prevent parasitic diseases, and vaccinations to deal with viruses. In 1969 the US Surgeon General William H Stewart reported to Congress that it was time to “close the book on infectious diseases”.

As an editorial in the inaugural Lancet Infectious Diseases put it, rather dryly:

Perhaps he [Stewart] should have known better. For infectious diseases are caused by living things, and living things are unpredictable and adapt to adverse environments. Organisms that occur in vast numbers and pass through many generations in a short time mutate and adapt quickly (10 billion bacteria will have mutations in about 1000 loci) relative to the plodding pace of human progress. As is human nature, confidence in our eventual victory over infectious diseases led to complacency, a complacency that pathogens were swift to exploit.

Today, despite  - or perhaps because of – the optimism of the mid-late 20th century, things look quite different to Stewart’s infamous prediction. Many diseases that we had thought to be under control are coming back with a vengeance, including TB, malaria, cholera, pneumonia and West Nile disease. Over the past 20 years,  strains of common microbes such as Staphylococcus aureus and Mycobacterium tuberculosis have continued to develop resistance to the drugs that once were effective against them. And there are worrying instances of disease emergence, some of which we barely understand: HIV-AIDS being by far the most significant, but also Ebola and other haemorrhagic fevers, hepatitis C, SARS, MERS and MRSA. A WHO report published in 2007 warned that infectious diseases are spreading more rapidly than ever before, and that new infectious diseases are emerging and re-emerging at a faster rate than any time in history.

How big a problem is this globally? According to CSIS, 16% of all deaths globally each year are due to infectious diseases. This of course varies changes by risk group and by country income levels. In 2010, researchers at John Hopkins found that infectious diseases cause almost two-thirds of all under 5 deaths globally. Based on calculations of WHO data and the charts below, we can see that the infectious disease burden is disproportionately borne by developing countries: while it may be a re-emerging problem in rich countries, it is safe to say that in poorer countries the problem never really went away.

- in low income countries, 38% of all deaths and 6 of the top 10 causes of death are accounted for by infectious diseases


- in low-middle income countries, 24 % of all deaths and 5 of the top 10 causes of death were due to infectious diseases


- in high income countries, 4% of all deaths and 1 of the top 10 causes of death were due to infectious disease


This data may justify a degree of complacency for those in rich countries. But even in high-income countries, as Dame Sally Davies has argued, infectious diseases cannot be dismissed. In the UK in 2011, infectious and parasitic diseases were responsible for over 200,000 admissions to National Health Service hospitals in England , and this was an increase of 10% on the previous year, and 84% since 2007, confirming a clear rising trend.

This overall scenario is an echo of what leading epidemiologist David Waltner-Toews once described to me as a new major global challenge: an ‘epidemic of epidemics’.

So what should we be doing in response? Last month, a number of top scientists argued that the evolution of microbes in the face of medical treatments is “in many ways… similar to climate change. Both are processes operating on a global scale for which humans are largely responsible.”  The same paper bemoaned the “feeble” international response to date, and called for a new intergovernmental panel to address the problem.

The idea is that, just like the IPCC, the proposed new panel will bring together global expertise to fight the drastic threats posed by the resistance of microbial pathogens of all kinds – from HIV and malaria to MRSA and TB . This new body is seen as vital because no single existing organisation is seen to have the breadth of knowledge or scope necessary to deal with the problem.

We will have to wait and see whether this call will have any traction in a global policy landscape which is already overburdened with conflicting priorities. Judging by the experience of the IPCC, even if such an institution is successfully established, we will not be closing the book but merely at the start of a new chapter in our ages-old battle against infectious diseases.

‘Sensible measures’ or ‘Crazy and irresponsible’? Read and have your say.

The 1918 influenza pandemic which killed 50 million people worldwide, has been described as “the greatest medical holocaust in history”. One of the enduring mysteries is how and why the flu was so virulent. Theories abound (some of which I will explore in a future post).

A lot of press attention in the past 24 hours has been directed to news that scientists at the University of Wisconsin at Madison have recreated a life-threatening virus which is only 3% different to the one behind the 1918 pandemic.

The arguments against this development are forthright: that to do so was irresponsible and potentially devastating.

The arguments for the work are rather less aggressive: what if an comparable epidemic happens naturally, and we find ourselves unprepared?

Below is an extract from yesterday’s Guardian article on the issue:

Scientists at the University of Wisconsin-Madison used a technique called reverse genetics to build the virus from fragments of wild bird flu strains. They then mutated the virus to make it airborne to spread more easily from one animal to another.

“The work they are doing is absolutely crazy. The whole thing is exceedingly dangerous,” said Lord May, the former president of the Royal Society and one time chief science adviser to the UK government. “Yes, there is a danger, but it’s not arising form the viruses out there in the animals, it’s arising from the labs of grossly ambitious people.”

Influenza viruses circulate freely in wild bird populations. Most remain in chickens, ducks and other birds, but occasionally strains mutate into a form that can infect humans. The H5N1 bird flu strain has killed at least 386 people since 2003, according to WHO figures. The Spanish 1918 flu is thought to have come from birds too. Writing in the journal Cell Host and Microbe Yoshihiro Kawaoka describes how his team analysed various bird flu viruses and found genes from several strains that were very similar to those that made up the 1918 human flu virus. They combined the bird flu genes into a single new virus, making a new pathogen that was only about 3% different from the 1918 human virus.

The freshly made virus – the first of several the team created – was more harmful to mice and ferrets than normal bird flu viruses, but not as dangerous as the 1918 strain. It did not spread between ferrets and none of the animals died. But the scientists went on to mutate the virus, to see what changes could make it spread. Seven mutations later, they had a more dangerous version that spread easily from animal to animal in tiny water droplets, the same way flu spreads in humans. Kawaoka, who led the research in a high-security lab at the University of Wisconsin-Madison, said the work highlighted how flu viruses found in wild bird populations had the potential to adapt to humans and cause a pandemic. Follow-up experiments showed that the 2009 swine flu vaccine and the anti-viral drug tamiflu should be effective against the virus. “This is important information for those making decisions about surveillance and pandemic preparedness,” Kawaoka told the Guardian.

The work is the latest in a series of controversial studies that have split the scientific community. On the one side are researchers who create dangerous viruses in secure labs in the hope of learning how existing strains could mutate to make them a potential threat to humans. On the other are scientists who argue the work does little or nothing to help protect people, but instead puts the global population in more danger. Marc Lipsitch, professor of epidemiology at Harvard School of Public Health, said: “I am worried that this signals a growing trend to make transmissible novel viruses willy-nilly, without strong public health rationale. This is a risky activity, even in the safest labs. Scientists should not take such risks without strong evidence that the work could save lives, which this paper does not provide,” he added. In an article published last month, Lipsitch argued that experiments like Kawaoka’s could unleash a catastrophic pandemic if a virus escaped or was intentionally released from a high-security laboratory.

But Kawaoka defended the work, saying that critics failed to appreciate the impact of his and others’ work on dangerous viruses. “There were discussions on the usefulness of stockpiling H5N1 [bird flu] vaccines until our H5N1 papers were published. Similarly, this paper strongly supports stockpiling anti-influenza drugs. If this is not a ‘lifesaving benefit’, what is?” he said. Many of the groups that create dangerous viruses to understand their workings are funded by the US National Institutes of Health (NIH). Lord May said he suspected the NIH supported the work because officials there were “incompetent” and believed the justifications that scientists told them. “This is work that shouldn’t be done. It’s as simple as that,” he said.

I have my own views on this, but am interested to know what readers think.

How Not To Beat Malaria


…History repeats itself. While malaria rates went down again as a result of insecticide-treated mosquito nets and widespread deployment of artemisinin-based combination therapies, the parasite adapted its genetic machinery to resist these powerful medicines and is now preparing for a devastating return…

If P. falciparum becomes totally resistant, then the ACTs would become ineffective and all investments in their development and distribution would be lost, with dire consequences….

Over the years, millions of dollars have been spent on fighting malaria… But all this well-intentioned money keeps us only a step ahead of the parasites. We have to keep coming up with new combinations of drugs before our patients taking the old ones start dying. And bed nets… aren’t always effective here in Southeast Asia, where many mosquitoes that carry the parasite bite outside and early in the evening.

Of course, an effective vaccine could save us but, despite the frequent announcements that we’re close to developing one, it has never materialized because we do not fully understand the underlying biology. We have to accept that these strategies of control are failing…

The more money we throw at malaria, the bigger the problems get…

Francois Nosten, Professor in Tropical Medicine at Oxford University, and leader of the largest ever drug trials on malaria, writing in the NYT  this week.



Welcome to The Third Transition blog

Today, I start a new blog called The Third Transition. The objective is to explore how and why infectious diseases are re-emerging as a major global threat to humanity, and what we might do about it.

What is the Third Transition?

The Third Transition refers to the latest in a series of macro-historical transformations in the relationship between humankind and our greatest, most successful, most enduring, predators: microbial pathogens.

The First Transition started with the agricultural revolution, some 10,000 years ago. The ability to produce food and the domestication of animals removed our reliance on hunting and foraging. This new-found skill introduced a host of zoonotic diseases and nutrient deficiencies and increased encounters with vectors during farming activities. This was intensified with the rise of cities, trade, travel and global conquest.

The Second Transition began in early industrial nations some 200 years ago, with the dawn of modern medicine, and the accompanying belief that infectious diseases could be consigned to history. Significant advances in public health and nutrition raised life expectancies, but this demographic shift also saw a rise in the incidence of non-communicable and chronic diseases such as heart diseases, cancers and diabetes as the major causes of ill-health and death.

The Third Transition is what much of the world is now moving into – what has been referred to as a new age of infectious diseases. We are seeing a rise in new emerging microbial pathogens and the resurgence of infectious diseases that had been though defeated, particularly due to drug resistance. In this age, microbial pathogens have a heightened ability to adapt and spread rapidly thanks to social and economic globalisation.

What is this blog about?

The Third Transition blog will have three broad themes:

1) The history of disease that has led us to the brink of the aforementioned Third Transition:

  • key evolutionary and ecological principles and how they shape disease emergence and resurgence
  • how these principles apply to different diseases and how they have shaped the course of human history
  • what the ‘Third Transition’ means in terms of the ‘new epidemic age’ and our common future

2) The global social, economic, environmental, political and technological drivers of disease in the 21st century:

  • impoverishment and inequality
  • trade and travel
  • farming and food production
  • land-use and environmental degradation
  • drugs and medical regimes.

3) The innovations that can help us deal with the Third Transition:

  • computational, big data and open approaches to health R&D;
  • evolutionary, stewardship-based approaches to medical practice;
  • ecological and systemic approaches to building disease resilience.

Who is this blog for?

This blog is for anyone with an interest in global health, environmental change, international development, and the limits and possibilities of science and medicine.



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