Question for short debate (Lords) on Antimicrobial Resistance - Mar 8

Baroness Greengross 

To ask Her Majesty’s Government what assessment they have made of the risks of antimicrobial resistance.

Baroness Greengross (CB) 

My Lords, I declare an interest as the CEO of the International Longevity Centre-UK, which has done quite a lot of work on the issues that we are discussing. Antimicrobial resistance poses an unprecedented threat to human health. As bacteria become resistant to antibiotics, even minor infections have the potential to become serious and indeed fatal. The rise of drug-resistant infections is estimated to account for around 700,000 deaths per year worldwide, with 50,000 of those deaths occurring within Europe and the United States.

I am sure that noble Lords will be familiar with the review of the noble Lord, Lord O’Neill, on antimicrobial resistance, published in 2016, which projected that by 2050 global mortalities due to this could reach 10 million a year and cost the global economy £66 trillion in lost productivity. The Chief Medical Officer, Dame Sally Davies, has also shared her concerns that the recent era of material mortality improvement will give way to many years of material mortality worsening if drug-resistant infections continue to develop at current rates. Willis Towers Watson’s head of mortality and longevity has calculated that a “plausible” worst-case scenario for the development of antimicrobial resistance will,

“largely zeroise or even negate”,

the longevity improvements made since the mid-20th century.

Fortunately, there have been some developments in the global effort to reduce the spread of AMR. The Access to Medicine Foundation’s 2018 Antimicrobial Resistance Benchmark report found that nine life sciences companies are active in antimicrobial resistance surveillance programmes covering 147 countries between them. There are also currently 28 antibiotics for high-priority pathogens in late-stage development. However, in other areas there is cause for concern as progress seems to have stalled.

A freedom of information request issued to Public Health England in 2017 found that prescriptions of colistin, the last line of defence in antibiotic treatment, rose by 40% between 2014 and 2015, from 346,000 doses to 485,000. Antimicrobial resistance was common in the more than 1 million urinary tract infections caused by bacteria identified in NHS laboratories in 2016. Some progress was observed in reducing rates of prescribing in secondary care in 2015, but there has not been a sustained reduction in total antibiotic prescribing in this care setting. While antibiotic prescribing reduced by 5% overall between 2012 and 2016, when measured as defined daily doses per 1,000 inhabitants per day, significant regional variation in antibiotic use continues to occur.

Unfortunately, there is also significant regional variation in the uptake of a crucial means of preventing the spread of antimicrobial resistance—I am talking about vaccination. The review by the noble Lord, Lord O’Neill, noted that vaccine programmes can reduce antibiotic consumption by preventing secondary infections and that, in addition, they often save society more than 10 times their original cost by protecting against vaccine-preventable diseases.

A study conducted jointly by the Department of Health and Social Care, the Norwegian Institute of Public Health and the South African directorate of health estimated that universal coverage with pneumococcal conjugate vaccine could avert up to 11.4 million days of antibiotic therapy annually worldwide in children younger than five years of age. A separate study published in the Journal of Clinical Infectious Diseases and Practice found that the introduction of a universal influenza immunisation programme for everyone aged six months and over in Ontario in the year 2000 resulted in a 64% decrease in influenza-associated respiratory disease antibiotic prescriptions relative to other regions.

However, despite the demonstrable impact of vaccination on antibiotic prescription, there is significant regional variation in immunisation uptake rates. Uptake targets set by the Department of Health and Social Care are sadly being missed. Between September and December 2017 flu vaccine uptake among GP patients aged 65 and over varied from a high of 74% in Greater Manchester to only 64.9% in London. Between September 2016 and August 2017 shingles vaccine coverage in the routine cohort—those aged 70—declined 13.5% since the start of the programme to 48.3%. I can speak personally about that vaccine. With shingles about to descend into my eye, it was so quick in getting rid of it. It was extraordinary and I am very wedded to this.

The coverage rate for the infant pneumococcal vaccination programme is now sadly below the 95% national target adopted by the Department of Health and Social Care. Given that the coverage level in the UK is already falling, it is worrying that the Government might deprioritise pneumococcal immunisation following a recent proposal to remove a dose of the vaccine from the infant pneumococcal immunisation programme. This advice has recently been consulted on, so it is to be hoped that in the interests of public health, the Government will consider the views of stakeholders closely, including the potential impact of a reduced schedule on antimicrobial resistance before making any policy decisions. The Government could also consider how they can ensure that the NHS benefits from future vaccines targeted at preventing hospital-acquired infections such as MRSA and C. difficile, which are of particular relevance to AMR. The Government should consider how tackling AMR can be incorporated into decision-making processes about the introduction of vaccination programmes.

Finally, given that the Civil Contingencies Secretariat 2017 national risk register categorises antimicrobial resistance and climate change as long-term trends that pose severe risks to the UK, I would urge that each of us should approach the problem of antimicrobial resistance with the same urgency and vigour as the threat posed by climate change.

Lord Colwyn (Con) 

My Lords, I congratulate the noble Baroness on securing this debate on the risks of antimicrobial resistance, or AMR. Although it is last on the list of the short debates this afternoon, this debate follows quite nicely on from the debate we had on 22 November last year when we discussed the same sort of problems. The standard of wound care was the main subject then.

The global threat of AMR, in both human and economic cost, has been well documented. I will not repeat the statistics of the grave consequences that are predicted if we do not act. I shall have to read what the noble Baroness said. It sounded terribly complex, but I will catch up with it tomorrow.

As noble Lords will know from past debates, I have been a champion of research and development to create new treatments so that we can get ahead of the superbugs. I have been greatly impressed by the work of Matoke Holdings. This small British biotech firm has pioneered reactive oxygen technology, a novel antimicrobial, initially as a treatment for serious infected wounds. This could be ground-breaking in tackling antimicrobial resistance. I do not have any financial interest to declare, but I have an interest in that my younger brother recently lost a leg from MRSA and the remaining leg was successfully treated with reactive oxygen technology. Professor Davies has warned in the past of apocalyptic consequences if antibiotics stop working. Overuse of antibiotics is speeding up the rate at which bacteria evolve, making common infections much more difficult to treat. With a lack of significant investment in antimicrobial R&D from big pharma companies, it falls to small and medium-sized enterprises, such as Matoke, to put in the leg work to develop new products to meet the global AMR challenge. However, for SMEs in particular, the cost and timescale of the R&D process is a significant challenge.

I was pleased to see in the Government’s response to the Accelerated Access Review at the end of last year the announcement of a new accelerated access pathway to support R&D for the most innovative products. The pathway will designate around five breakthrough products a year, which will receive bespoke support from government to take new innovations from lab bench to bedside. Given that there have been no new antibiotics in the past 30 years, the pathway is an excellent opportunity to speed up the development of new antimicrobials and to get ahead of the AMR threat. Will the Minister confirm whether the pathway will prioritise novel antimicrobials when allocating breakthrough product status? Will the Minister join me in meeting Matoke to get a first-hand account of the challenges faced by SMEs on the front line of the struggle against AMR?

Baroness Suttie (LD) 

My Lords, I, too, thank the noble Baroness, Lady Greengross, for securing this extremely important and timely debate. I begin by declaring an interest as vice-chair of the APPG on Global Tuberculosis, and I refer noble Lords to my interests as set out in the register and my work with the Global TB Caucus. I will, perhaps not surprisingly, concentrate my remarks this afternoon on tuberculosis and multidrug-resistant TB.

The review on AMR by the noble Lord, Lord O’Neill, estimated that one-third of all AMR-associated deaths are currently caused by drug-resistant TB. In 2016, an estimated 600,000 people developed drug-resistant TB. While rates are going down gradually, drug-resistant TB rates continue to rise in some parts of the world. This situation is particularly true in Europe, which has seen the fastest growing rates of multidrug-resistant TB of any world region. Although it has the lowest TB incidence, it has the highest rates of MDR TB. Of the almost 300,000 cases of TB in Europe last year, more than 120,000 were drug-resistant. I should say at this point that this is the European region as defined by the World Health Organization, which includes the central Asian countries of the former Soviet Union. In other words, well over one-third of all TB cases in Europe last year were drug-resistant.

Of the 30 countries identified as having the highest rates of drug-resistant TB, nine are in the European region and the countries of the former Soviet Union. The reasons for the particularly high levels of TB and MDR TB in the countries of the former Soviet Union are complex: steep economic decline and the sharp rise in poverty in the 1990s, when the Soviet Union collapsed; the disintegration of the Soviet healthcare system; an HIV epidemic; very high prison populations and dilapidated prison facilities; and the excessive hospitalisation of patients who are no longer infectious as they have been taking their medication. In addition, since independence, many of these countries have seen significant deregulation of pharmaceutical provision and the ready availability of antibiotics to buy in privatised kiosks, often without a doctor’s prescription, throughout the cities of the former Soviet Union. In some countries, there are also difficulties in securing newer drugs available to treat MDR TB, from which patients could greatly benefit.

With the Global TB Caucus I have been visiting many of these countries over the past 18 months to try to raise awareness of multidrug-resistant TB and its causes among parliamentarians in the countries of the former Soviet Union, to encourage them to set up parliamentary groups like APPGs in their own Parliaments and to work with civil society organisations and their health ministries to take action against drug-resistant forms of TB. Clearly, the APPG in this department has very similar aims.

The noble Lord, Lord O’Neill, in his review of AMR, recommended as a first intervention that there should be a global public awareness campaign. Will the Minister say how successful he thinks this public awareness campaign has been up until now, and what further measures the Government intend to take to achieve this goal? Drug-resistant strains of TB are more expensive to treat because of the cost of medicines, the length of treatment and the amount of additional support required by each patient to manage side effects. I have spoken to many patients with drug-resistant TB in Ukraine and central Asian countries, as well as here in the UK, and they have told me of the difficulties of swallowing up to 20 pills a day, along with painful injections and the side effects to their mental and physical health of having to cope with such a harsh regimen, often for a period of 18 months or more. Considerable support networks are required to ensure that patients continue with their treatment and, clearly, not continuing with the treatment adds to the risk of developing a form of TB which is even more drug-resistant.

There have been relatively few advances in finding new treatments which work more effectively and more quickly against drug-resistant TB, which leads me to my second question to the Minister. What measures do the Government intend to take to incentivise the production of new and more effective antibiotics for TB, and multidrug-resistant TB in particular? The Global TB Caucus estimates that $1 trillion will be lost to the global economy between 2015 and 2030 if no major steps are taken. Increases in rates of MDR TB can put a massive strain on healthcare systems and national economies. KPMG predicts that Europe could be due to lose nearly 0.02% of its economy between 2015 and 2050 due to MDR TB alone should urgent action not be taken.

In autumn this year the United Nations will hold a high-level meeting on TB. This represents a significant opportunity to adopt a concerted international effort to tackle multidrug-resistant TB. Will the Minister say what preparations the Government are currently making to prepare for this high-level meeting?

I will end with a quote from the review by the noble Lord, Lord O’Neill:

“The burden of TB is too great, and the need for new treatments too urgent, for it not to be a central consideration in the role and objectives of a global intervention to support antibiotic development”.

Baroness Masham of Ilton (CB) 

My Lords, I thank my noble friend Lady Greengross for securing this short debate. It may be short but it is of tremendous importance globally. AMR is widely recognised as the biggest threat we face.

Many years ago I was the first person in your Lordships’ House to have a debate on MRSA, after the late Lord Gerry Fitt’s wife died from MRSA in the Chelsea and Westminster Hospital. After that, along with a group from the Science and Technology Select Committee, I went to America to look at the problems around antimicrobials and infection. One of our recommendations was that there should be quick tests for infections so that the correct antibiotic can be prescribed. This is now happening in some places, and that is good news.

The famous physician, Sir William Osler, who is sometimes described as the father of modern medicine, said in 1892 that there are three phases to treatment: diagnosis, diagnosis and diagnosis. In modern times, diagnostics are vital to guiding clinical decision-making, determining whether a patient should be treated with antibiotics, and if so, which ones will be effective.

Sepsis is a bigger killer in the UK than bowel, breast and prostate cancer combined. With the increasing challenges of antimicrobial resistance, it is more important than ever for hospitals to diagnose accurately and rapidly so that patients with sepsis can be treated. The lack of consistency across UK hospitals in their diagnosis of sepsis has been highlighted. Research has found that 56% of hospitals are using only one set of blood cultures where sepsis is suspected rather than the recommended two sets. This leads to much less chance of the successful identification of the bacterium involved.

World Tuberculosis Day is approaching, so I thought it appropriate to remind your Lordships that TB remains the world’s deadliest infectious disease, with 10.4 million people infected and 1.7 million dying from the disease in 2016. In his review on AMR, the noble Lord, Lord O’Neill, estimated that around a third of all AMR-associated deaths are caused by drug-resistant TB. The UK itself struggles with TB and has been known as the drug-resistant capital of northern Europe. I join with the noble Baroness, Lady Suttie, in her remarks on this very important subject.

Until recently, doctors relied on the microscope to identify TB and it took months of growing cultures in laboratories to determine if the strain of TB was drug resistant. However, things have changed for the better with the production of the GeneXpert TB testing machine, which can analysis DNA. The test can identify whether someone has TB and can detect whether there is resistance to one of the main TB drugs, rifampicin. The UK Government have been central to advancing this technology by making a significant investment in it through the Ross Fund. Scientists and policymakers are working to improve this diagnostic tool and ensure that it is used as widely as possible.

The availability of a rapid diagnostic test is vital to fighting AMR and will ensure that those who need antibiotic treatment urgently receive it. It will also ensure that antibiotic drugs are not misused or prescribed inappropriately, thus driving further drug resistance. This is also important to animal health and farming. Exciting research in this field is going on around the world and certain new technologies are now able to determine antimicrobial resistance in as little as 30 minutes. We must invest to drive forward the research and development that will protect patients and the public.

Concern has been expressed about outbreaks of multiresistant hospital bacteria among newborns in hospitals, including in neonatal intensive care and special care baby units. Controlling MRSA has been improved due to hard work, but in high dependency care units where patients are more vulnerable to drug-resistant infections, the risks are great. Is anything being done to systematically collect the data, identify improvements that can be made and fund the emerging diagnostic and monitoring technologies that enable a rapid infection control response?

Another problem that needs addressing is the epidemic of Clostridium difficile-associated diarrhoea in hospital patients, largely attributable to antibiotic overuse. Good work is being done, but it is translation into practice that seems all too slow.

Finally, does the Minister agree that the European Vaccine Action Plan is of great importance? With more and more infections becoming immune to antibiotics, it is vital to prevent conditions such as gonorrhoea, which is resistant to antibiotics and needs a vaccine, as do norovirus, Clostridium difficile, HIV and many others, and a better vaccine is needed for TB. That would make the world a safer place for everyone.

Baroness Sheehan (LD) 

My Lords, I add my thanks to the noble Baroness, Lady Greengross, for introducing this debate on such an important matter.

The seriousness of this issue was stated starkly by the Chief Medical Officer, Professor Dame Sally Davies, who said that if we do not act, it is possible that we will return to 40% of the population dying prematurely from infections that we cannot treat. The sad fact is that overuse and misuse of antibiotics and other antimicrobials in humans, animals, including farmed fish, and crops have been major contributors to an acceleration in the emergence of drug-resistant strains of bacteria, viruses, parasites and fungi. The noble Baroness, Lady Masham, referred very powerfully to the role that better diagnostics can play in enabling us to use antimicrobials with circumspection. I concur with her completely.

When the review on AMR, led by the noble Lord, Lord O’Neill, was published in May 2016, it generated a much-needed urgent focus on the issue, leading to a commitment to act by world leaders at the high-level meeting of the UN General Assembly on AMR in September 2016. Countries reaffirmed their commitment to develop national action plans on AMR, building on the blueprint developed in 2015 by the World Health Organization, the FAO and the World Organisation for Animal Health.

The fact is that common and life-threatening infections such as pneumonia and gonorrhoea, and post-operative infections, as well as HIV, TB and malaria, are increasingly becoming untreatable. Very worrying is the fact that cases of completely untreatable gonorrhoea have been recorded in the last year in developed countries.

I shall concentrate the rest of my remarks on international development, which is the brief on which I speak for my party, the Liberal Democrats. TB is a disease that kills 1.8 million people a year. My noble friend Lady Suttie has already spoken passionately about the rise of multidrug-resistant TB globally. Last August I was in Liberia and, courtesy of RESULTS UK, I visited a clinic where patients with multidrug-resistant TB were being treated. As my noble friend Lady Suttie said, the treatment is complex, very costly and toxic. It can last from six to 30 months and can consist of more than 14,000 pills and daily injections for six months. What was clear to me was that the patients I met were the lucky ones and that many more in the community potentially carried MDR-TB because the resources to carry out comprehensive tracing were just not there.

What is urgently needed is a vaccine for TB. Prevention would obviate the need for treatment with antibiotics and give us a chance to eradicate the disease. However, the development of vaccines is a lengthy process, so recent progress is at risk unless vital investment is provided with a long-term commitment to give developers—in particular, product development partnerships—the confidence to plan for the future with certainty. I fully echo the words of the noble Lord, Lord Colwyn, on that. The UN high-level meeting on TB this September offers a rare chance to turn the tide against TB and I hope the Government will take the opportunity to drive the vaccine agenda forward.

Malaria is another long-time scourge of the developing world and now the problem is compounded by the discovery of drug-resistant mosquitoes in Myanmar, Thailand, Lao PDR, Vietnam and Cambodia. I draw the Minister’s attention to the extremely dangerous situation that exists in the Rohingya camps in Bangladesh, as identified by the Malaria Consortium—I declare that I am a trustee of that organisation. The monsoon rains are due next month and these, coupled with the combination of poor sanitation and emergency, substandard housing, will provide perfect breeding conditions for malaria-transmitting mosquitoes. The danger to the refugees is obvious, but what also needs to be considered in the mix is that the refugees have come from Myanmar, where malaria resistant to artemisinin-based antimalarials has been detected, including in the nearby Sagaing region. The native population of Cox’s Bazar in Bangladesh is highly vulnerable to malaria because the people have not been exposed to the disease recently. We can see the dangers inherent in that situation. We cannot risk the further spread of drug-resistant malaria and I ask the Minister to relay these concerns as a matter of urgency to the appropriate personnel. DfID is well placed to take action as a world leader in the fight against malaria and is already in place, combating diphtheria and cholera in the camps.

Prevention is always better and cheaper than cure. In its March 2016 report on limiting the spread of drug resistance, the AMR Review Board estimated that improved water and sanitation in middle-income countries could reduce the volume of antibiotics used to treat diarrhoea by at least 60%. We need to apply common sense and ensure that good housekeeping takes precedence over popping a pill. The availability of antimicrobials is shifting action away from prevention and the good practice of investing in basic sanitation infrastructure.

Previous speakers have spoken about market failures. We see that investment in developing new antibiotics has gone into reverse. We need new ways of stimulating innovation and to do that we must find a way to delink the cost of research and development from the price and volume of sales. How will the Government ensure that new antibiotics and other innovations are affordable to the NHS and health systems around the world? In the same vein, will the Minister comment on the progress of the UK and China Global AMR Research Innovation Fund?

To conclude, considering that we are in a global space where it is easy to spread AMR infections through trade and travel, and that resistance has been observed in terrestrial and aquatic environments, where wind and currents take them out of our control, we begin to see the scale of the problem we face. The fact is that we know what we have to do. Political will and leadership is what is needed now.

Lord Hunt of Kings Heath (Lab) 

My Lords, it is a great pleasure to wind up for the Opposition and thank the noble Baroness, Lady Greengross, for an excellent contribution, which other noble Lords added to. I want to raise two issues. One is about the use of antibiotics in animals and the other is about incentives for developing new drugs and vaccines. First, I refer to the wide-ranging speech of the noble Baroness, Lady Greengross, in which she referred to immunisation uptake, which is a very worrying issue for health in this country, let alone in other countries. I have seen various reports that there is ever more misinformation out there undermining people’s confidence in vaccines. We saw with the MMR issue the problems arising when this gains ground. Is the Department of Health and Social Care exercised about this and is it developing a strategy?

On the use of antibiotics in animals, I know that the Government made a progress report in 2016, commented on this and particularly referred to compliance with Red Tractor assurance scheme standards and to the work of the task force Responsible Use of Medicines in Agriculture Alliance. My noble friend Lord Grantchester, to whom I have referred on this, has made the point to me that, alongside this and influenced by various suppliers, farm assurance schemes are having a positive impact in reducing the use of antibiotics in animals. Will the Minister comment on this and give a progress report in that area?

On how better incentives can be used to promote investment in new drugs and vaccines, the report by the noble Lord, Lord O’Neill, was very clear that the current pipeline of new antibiotics shows that there is a mismatch between the drugs that the world needs and the number and quality of new antibiotics that are being researched. He recommended,

“a global system of market entry rewards for antibiotics and alternative therapies”.

He suggested that the challenge really is,

“to ‘de-link’ the profitability of an antibiotic from volumes sold, reducing uncertainty and enabling reward without encouraging poor stewardship”.

This arises from the fact that it is very difficult in the current model for the industry to see how it can get any return on the development of new antibiotics, and because of that, we have this very big problem.

I know that the Government have acknowledged the principle of de-linking, particularly in their endorsement of the 26th UN declaration on AMR but, just to reflect on the problem, STOPAIDS, which is a UK network of agencies which have developed a global response to HIV and AIDS, set out the de-linking issue, stating that the incentive to innovate is still tied to the price that pharma companies can charge for the products they create and therefore there is still a risk of continuing this problem of high price. The ABPI, the trade association for the pharma industry, is continuing to work with the noble Lord’s department on this to explore reimbursement and evaluation models, which could perhaps be piloted in the UK, but I wonder whether the noble Minister can say a little bit more about whether progress is being made.

I refer noble Lords to a recent—2018—report by the Access to Medicine Foundation, which is an international NGO based in the Netherlands. Very recently it produced an anti-microbial resistance benchmark. The report states that despite some progress being made by some companies, there are still too few in the pipeline and we need to strengthen that pipeline. I wonder whether there are other actions that now need to be taken to provide the right incentives.