By: AARON OXLEY
Executive Director, RESULTS UK

The discovery of penicillin changed the world. In 1928, Alexander Fleming revolutionized the way we see microbial infections by discovering the first antibiotic, a feat that ultimately awarded him the Nobel Prize in Physiology or Medicine in 1945. Penicillin has saved more than 200 million lives since its introduction in 1942.

But almost as soon as antibiotics were developed, resistance began to develop too. Now more than 70 years on, over-prescription, unnecessary agricultural use, and complicated treatment regimens are allowing organisms to survive exposure to the drugs designed to kill them. These resistant organisms spread, with drug resistant infections claiming over 50,000 lives a year in Europe and the US alone.1 Globally, we are seeing rates of so-called “superbugs” such as methicillin resistant.

Staphylococcus aureus (MRSA) skyrocket, with increased mortality rates and costly price tags. It is not just antibiotic resistance that is an issue as viruses such as HIV or parasitic infections such as malaria are becoming drug resistant, too. This highlights a technical but important distinction: antibiotic resistance is just a part of the broader problem of antimicrobial resistance (AMR).

Nowhere is this more important than in the progress humanity has made on eliminating infectious diseases. Diseases once thought to no longer exist in the developed world, such as TB and malaria, have the potential for a devastating return.

2016 has seen unprecedented and desperately needed international attention to AMR. Earlier this year there was the ground-breaking publications of the Review on Antimicrobial Resistance,2 led by Lord O’Neill, a UK Treasury Minister and former Goldman Sachs Chief Economist. Established by former UK Prime Minister David Cameron, the AMR Review’s mandate was to analyse and propose solutions to the rise of antimicrobial resistance.

The report concludes there is an almost inconceivable human burden and economic cost facing the world. It warns of an estimated 10 million AMR deaths every year by 2050, resulting in a reduction of 2-3.5 percent of in global GDP.3 Not only could the global economy be reduced by up to $100 trillion USD over the next 35 years, but without action standard operations and medical procedures may be deemed too dangerous to conduct due to the threat of an untreatable infection.

The world’s deadliest infectious disease becomes drug resistant.

We do not need to look far into the future to understand the consequences of ignoring this issue, because it is already here in the form of tuberculosis (TB)—one of the world’s oldest diseases and also the deadliest. TB has claimed more lives throughout history and claims more lives each year than any other infectious disease,4 and it is well along the path of becoming resistant to antibiotics. TB was placed firmly at the centre of the O’Neill review;

“Tackling TB and DR-TB must be at the heart of any global action against Antimicrobial Resistance. The burden of TB is too great and the need for new treatment too urgent.”

Over the last few decades, TB has been quietly transforming into new strains of drug resistant TB (DR-TB).** DR-TB causes an astounding 500 deaths a day and cannot be cured with standard TB drugs.5 As the only airborne drug resistant infection, the AMR Review estimates that TB has the potential to cause a quarter of all AMR deaths by 2050, with an estimated 75 million people dying from the disease over the next 35 years.

The economic cost of DR-TB will be astounding, estimated at $16.7 trillion by 2050. This is equivalent to the annual economic output of the EU,7 with one person dying from the disease every 12 seconds.8 The bacterium that causes TB disease is a hardy organism that takes months of daily treatment before being eliminated from the body, even with the best drugs available. This picture gets even more dismal when looking at treating DR-TB. Treatment can take up to two years, 14,000 pills and include eight months of painful injections. The strong but sometimes ineffective drugs are toxic, so treatment has the risk of adverse effects such as deafness, blindness, and in extreme cases, psychosis. This, coupled with the length of treatment means people often have difficulty finishing the full course of antibiotics, leading to the development of further resistance.

We have arrived at this point because no new drugs have entered the standard TB treatment regimen in nearly 50 years. Getting TB treatment down to days or weeks instead of months, and removing the most toxic drugs from our regimens would dramatically arrest the creation of DR-TB.

This requires the development of new drugs which will be difficult due to a chronic lack of pharmaceutical investment into antimicrobials. There was less than 5 percent of venture capital investment in pharmaceutical R&D between 2003 and 2013 for antimicrobial development.

There are over 9 million new cases of TB each year with almost half a million of those being a form of DR-TB, these people predominantly live in lower- or lower-middle-income countries, and are often themselves the poorest people in those countries. Their ability to pay for expensive new treatments is limited, and has not provided the necessary motivation for private-sector investment in TB R&D to date.

Ultimately, there is no way we will beat TB without a new vaccine. The current TB vaccine (the BCG) is almost 100 years old and not effective against the most common forms of the disease.10 A more effective vaccine could bypass drugresistance and be as game-changing as a new drug regimen. We must pursue both approaches simultaneously.

We know what the solutions are.

The AMR Review offers ten recommendations for addressing AMR around the world, including the development of a new fund to support basic academic research into new drugs and a pooled fund to provide a commercial incentive for private sector organizations to invest in new antimicrobials. This pooled fund includes the introduction of a market entry prize for a new TB regimen and individual antibiotics.

Encouragingly, the AMR Review emphasizes how important it is to ensure global access to any future and existing products. No solution to drug development is complete without getting the drug to the people who need it, including in low- and middle-income countries. New TB tools are no exception. A number of non-profit initiatives are already devoted to the search for more effective TB treatments, such as the TB Alliance for new drugs, and Aeras who is in the process of developing a TB vaccine. The recommendations made by the AMR Review will ”supercharge” these existing efforts by providing an incentive for new funders to invest in the development of TB medicines.

Looking upstream, providing funds for organizations that provide high-quality treatment that helps prevent the emergence of drug resistance is a powerful complimentary investment. Organizations like The Global Fund to Fight AIDS, TB and Malaria, or the Stop TB Partnership’s Global Drug Facility all contribute to this vital work.

An opportunity we cannot miss If increasing drug-resistance continues on its current trajectory, we may return to an era where treating simple infections becomes practically impossible. This is, in some ways, already true for TB and the scale of the human and economic impact that TB creates, means we urgently need new tools right now.

There is already an international action plan to tackle AMR led by the WHO as well as a collaboration between the United Kingdom, the European Union, the United States and others. AMR is on the agenda of this year’s G20 in China with countries agreeing to coordinated international action. However, just as the microbes that increasingly threaten us all are global in nature, we need more than the G20’s leadership. We need a global response from all states and their governments.

On 21 September, 2016, a crucial high level meeting on AMR at the UN General Assembly will take place. This meeting provides a unique opportunity to make a step change in global levels of awareness of AMR among politicians, professionals and the public.

More than words and promises, G20 leaders and the global community must act quickly to implement the AMR Review’s recommendations. This means fully funding new mechanisms for incentivising the development of drugs, diagnostics, and vaccines needed to defeat AMR. Failure to fully fund these mechanisms is to invite a catastrophe that will strike indiscriminately in an incredibly costly yet entirely predictable way. We can, and must, prevent this.