The Review on Antimicrobial Resistance, chaired by Jim O’Neill, was commissioned by former UK prime minister, David Cameron, in July 2014. Supported by the UK government and the Wellcome Trust, the final report of the review was published in May 2016 and has had a global impact in terms of motivating political leaders and decision-makers to take more seriously the threat posed by antimicrobial resistance.

Yet there is now a perception that the political momentum to address the issue is waning and needs to be reinvigorated.

In a further report produced by Chatham House, the progress of the recommendations of the review is assessed and the key ways to move forward are identified.

Panellists at this event, where highlights of the report are presented, provide their assessment of the progress so far and discuss priorities for future action.

The report was funded by Wellcome.

• The 2016 Review on Antimicrobial Resistance has had a global impact: as an advocacy tool, in raising the profile of antimicrobial resistance (AMR) on the international agenda, and in helping to stimulate a number of new initiatives, in particular relating to the funding of early-stage research.
• However, there has been very little progress on the review’s central and most expensive recommendations for transforming research and development incentives for antibiotics, vaccines and diagnostics.
• There have been significant advances in reducing antibiotic use in agriculture, particularly in high-income countries, but there is a long way to go in low- and middle-income countries (LMICs).
• There has been greater investment in awareness raising but questions remain about its impact and effectiveness in changing behaviour.
• Proposals to restrict over-the-counter sales of antibiotics, as recommended by the Review, have foundered in the face of poor living conditions and access to healthcare in LMICs.
• A major reason for the use of antibiotics in LMICs is the prevalence of unhygienic conditions in the community and in healthcare facilities, which contribute to infection and limit the impact of messages about awareness and infection prevention and control.
• Providing quality healthcare to all and moving towards universal health coverage in LMICs will be crucial in addressing the problems of both adequate access to antibiotics and in restricting over-the-counter sales.
• A greater emphasis on investments in water, sanitation and housing will be central to reducing reliance on antibiotics in LMICs in the longer term. This agenda should inform the operations of governments and funding agencies such as the International Monetary Fund (IMF) and the World Bank.
• Investments have been made in improving surveillance of antibiotic use and resistance, particularly for humans, but more effort is required to create surveillance systems that provide data sufficiently accurate to influence policy and action. This applies also to antibiotics and resistant genes circulating in the environment.
• The emerging innovations in the global governance of AMR need to lead to action rather than more words.

The leaked record of the five meetings of the UK–US Trade & Investment Working Group held in 2017–18 has led to a controversy in the UK election campaign around the claim that ‘the NHS is up for sale’.

But a careful reading of the leaked documents reveals how remarkably little concerns the NHS – in five meetings over 16 months, the NHS is mentioned just four times. The patent regime and how it affects medicines is discussed in more depth but largely in terms of the participants trying to understand each other’s systems and perspectives. For the most part, the discussions were overwhelmingly about everything else a trade deal would cover other than healthcare – matters such as subsidies, rules of origin and customs facilitation.

But this does not mean there will be no impact on Britain’s health service. There are three main concerns about the possible implications of a US–UK trade deal after Brexit – a negotiation that will of course only take place if the UK remains outside the EU customs union and single market and also does not reach a trade agreement with the EU that proves incompatible with US negotiating objectives.

One concern is that the US aim of securing ‘full market access for US products’, expressed in the US negotiating objectives, will affect the ability of NICE (The National Institute for Health and Care Excellence) to prevent the NHS from procuring products that are deemed too expensive in relation to their benefits. It could also affect the ability of the NHS to negotiate with companies to secure price reductions as, for instance, happened recently with Orkambi, a cystic fibrosis drug.

A peculiarity of the main US government healthcare programme (Medicare) is that it has historically not negotiated drug prices, although there are several bills now before Congress aiming to change that. US refusal to negotiate or control prices is one reason that US drug prices are the highest in the world.  

A second concern is that the US objective of securing ‘intellectual property rights that reflect a standard of protection similar to that found in US law’ will result in longer patent terms and other forms of exclusivity that will increase the prices the NHS will have to pay for drugs.

However, it is not immediately apparent that UK standards are significantly different from those in the US – the institutional arrangements differ but the levels of protection offered are broadly comparable. Recent publicity about a potential extra NHS medicine bill of £27 billion resulting from a trade deal is based on the NHS having to pay US prices on all drugs – which seems an unlikely outcome unless the UK contingent are extraordinarily bad negotiators.

Nevertheless, in an analysis section (marked for internal distribution only), the UK lead negotiator noted: ‘The impact of some patent issues raised on NHS access to generic drugs (i.e. cheaper drugs) will be a key consideration going forward.’

A third concern is that the US objective of providing ‘fair and open conditions for services trade’ and other US negotiating objectives will oblige the UK to open up the NHS to American healthcare companies.

This is where it gets complicated. At one point in a discussion on state-owned enterprises (SOEs) the US asked if the UK had concerns about their ‘health insurance system’ (presumably a reference to the NHS). The UK response was that it ‘wouldn’t want to discuss particular health care entities at this time, you’ll be aware of certain statements saying we need to protect our needs; this would be something to discuss further down the line…’

On this exchange the UK lead negotiator commented:  ‘We do not currently believe the US has a major offensive interest in this space – not through the SOE chapter at least. Our response dealt with this for now, but we will need to be able to go into more detail about the functioning of the NHS and our views on whether or not it is engaged in commercial activities…’

On the face of it, these documents provide no basis for saying the NHS would be for sale – whatever that means exactly. The talks were simply an exploratory investigation between officials on both sides in advance of possible negotiations.

But it is a fact that US positions in free trade agreements are heavily influenced by corporate interests. Their participation in framing agreements is institutionalized in the US system and the pharmaceutical and healthcare industries in the US spend, by a large margin, more on lobbying the government than any other sector does. Moreover, President Donald Trump has long complained about ‘the global freeloading that forces American consumers to subsidize lower prices in foreign countries through higher prices in our country’.

It is when (and if) the actual negotiations on a trade deal get under way that the real test will come as the political profile and temperature is raised on both sides of the Atlantic.

The world’s second-largest Ebola outbreak is ongoing in the Democratic Republic of the Congo (DRC) and experts from around the world have been parachuted in to support the country’s operation to stamp out the outbreak. The signs are encouraging, but we need to remain cautious.

In such emergencies, little thought is usually given to what happens to the body-fluid samples taken during the course of the outbreak after the crisis is over. What gets left behind has considerable implications for global biosecurity.

Having unsecured samples poses the obvious risk of accidental exposures to people who might come into contact with them, but what of the risk of malicious use? Bioterrorists would have ready access to materials that have the characteristics essential to their purpose: the potential to cause disease that is transmissible from person to person, the capacity to result in high fatality rates and, importantly, the ability to cause panic and social disruption at the very mention of them.

Comparisons can be drawn with the significant international impact of the anthrax attacks in the US in 2001. Not only was there a direct effect in the US with five deaths and a further 17 people infected, but there was a paralysis of public health systems in other countries involved in the testing of countless samples from the so-called ‘white-powder incidents’ that followed.

Many laboratory tests were done purely on a precautionary basis to eliminate any possibility of a risk, no matter how remote. However, the UK was also hit when a hoaxer sent envelopes of white powder labelled as anthrax to 15 MPs.

The threat of the pathogen alone resulted in widespread fear, the deployment of officers trained in response to chemical, biological, radiological and nuclear incidents and the evacuation of a hospital emergency department.

We learned from the 2014–16 West Africa Ebola outbreaks that during the emergency, the future biosecurity implications of the many thousands of samples taken from people were given very little consideration. It is impossible to be sure where they all are and whether they have been secured.

It is widely recognized that the systems needed at the time for tracking and monitoring resources, including those necessary for samples, were weak or absent, and this has to be addressed urgently along with other capacity-building initiatives.

In Sierra Leone, for example, the remaining biosecurity risk is only being addressed after the fact. To help achieve this, the government of Canada is in the process of providing a secure biobank in the Sierra Leonean capital of Freetown. The aim is to provide the proper means of storage for these hazardous samples and to allow them to remain in-country, with Sierra Leonean ownership.

However, it is already more three years since the emergency was declared over by the then director-general of the World Health Organization (WHO), Margaret Chan, and the biobank and its associated laboratory are yet to be fully operational.

There are many understandable reasons for this delay, including the critical issue of how best to ensure the sustainability of any new facility. But what is clear is that these solutions take time to implement and must be planned for in advance.

The difficulties of responding to an outbreak in a conflict zone have been well documented, and the frequent violence in DRC has undoubtedly caused delays in controlling the outbreak. According to figures from WHO, during 2019 approximately 390 attacks on health facilities in DRC killed 11 and injured 83 healthcare workers and patients.

Not only does the conflict inhibit the response, but it could also increase the risk posed by unsecured samples. There are two main potential concerns.

First is the risk of accidental release during an attack on a health facility, under which circumstances sample containers may be compromised or destroyed. Second is that the samples may be stolen for malicious use or to sell them to a third-party for malicious use. It is very important in all outbreaks to ensure the necessary measures are in place to secure samples; in conflict-affected areas, this is particularly challenging.

The sooner the samples in the DRC are secured, the sooner this risk to global biosecurity is reduced. And preparations for the next emergency must be made without further delay.

The following steps need to be taken:

• Affected countries must ‘own’ the problem, with clear national government commitment to take the required actions.
• Funding partners must coordinate their actions and work closely with the countries to find the best solutions.
• If samples are to be kept in-country, secure biobanks must be established to contain them.
• Sustainable infrastructure must be built for samples to be kept secure into the future.
• An international agreement should be reached on the best approach to take to prepare for the aftermath of global health emergencies.

When it comes to emerging infectious diseases – those newly recognized in humans or in new locations – it is not only what we know that matters but also what we do not know.

An outbreak of a new coronavirus first reported in Wuhan, China, which has so far led to more than 500 confirmed cases and multiple deaths across five countries (and two continents) has prompted the question from several corners of the world: Should we be worried?

Although expert teams coordinated by the World Health Organization (WHO) are working on key questions to get answers as soon as possible, the level of uncertainty is still high.

We do not yet know exactly how deadly the disease is, how best to treat those who get sick, precisely how it is spreading, nor how stable the virus is. It is thought that the virus spread from an animal source, but the exact source is yet to be confirmed and the disease is now in human populations and appears to be spreading from human to human.

It is such uncertainty, inherent in emerging infectious disease outbreaks, that warrants concern. Until they are resolved, it is appropriate for the world to be concerned. It is useful to remember that most established scourges of humanity such as HIV, influenza and tuberculosis likely started as emerging infectious diseases that jumped the species barrier from animals to humans.

Shortly after the Chinese authorities reported the first cases of ‘mystery pneumonia’ in Wuhan, China, to WHO, the virus causing the disease was isolated and identified as being part of the coronavirus family. It belongs to the same virus family as SARS, a highly contagious and life-threatening coronavirus that caused a nine-month epidemic in 2003 that affected 26 countries and resulted in more than 8,000 infections and nearly 800 deaths.

A second novel coronavirus that emerged in 2012 and persists today – MERS, or Middle East Respiratory Syndrome – is less contagious (spread by close contact rather than coughing and sneezing).

The differences between the SARS coronavirus and the MERS coronavirus highlight that, despite belonging to the same virus family, pathogens do not necessarily behave in the same way. It is as yet unknown whether the new virus is, or will turn out to be, more like SARS or MERS, or neither. 

Chinese authorities have confirmed that there is human-to-human transmission. However, it is not yet established whether it is sustained, which would make the outbreak more difficult to control. As of 23 January, the number of cases range from 500 confirmed cases up to an estimated 1,700 cases, according to a disease outbreak model by Imperial College London.

Likewise, we do not know to what extent the virus is able to mutate and if so, how rapidly. Generally, coronaviruses are known to be able to mutate, with the risk that a less contagious form of the virus becomes highly contagious. This could have an impact not only on the transmission pattern and rate but also the death rate. The virus could change in either direction, to become either more or less of a threat.

It is important to take a precautionary approach while uncertainty persists. It is also important not to overreact and for measures to be scientifically sound. Concern over this outbreak is due, but panic is not.

Three virtual networks of experts supporting the response – one of virologists, one of epidemiologists and one of clinicians – are working on the key pieces of the jigsaw puzzle: watching the virus, watching the transmission patterns, and watching the people who have been infected. It is crucial to maintain the ongoing investigation of the disease, stay focused on the science and to keep sharing the necessary information.

Donald Trump is impulsive. His sudden decision to stop funding the World Health Organization (WHO) just days after calling it 'very China-centric” and 'wrong about a lot of things' is the latest example. And this in the midst of the worst pandemic since Spanish flu in 1918 and a looming economic crisis compared by some to the 1930s. 

But the decision is not really just about what WHO might or might not have done wrong. It is more about the ongoing geopolitical wrangle between the US and China, and about diverting attention from US failings in its own response to coronavirus in the run-up to the US presidential election.

It clearly also derives from Trump’s deep antipathy to almost any multilateral organization. WHO has been chosen as the fall guy in this political maelstrom in a way that might please Trump’s supporters who will have read or heard little about WHO’s role in tackling this crisis. And the decision has been widely condemned in almost all other countries and by many in the US.

What is it likely to mean in practice for WHO?

Calling a halt to funding for an unspecified time is an unsatisfactory halfway house. A so-called factsheet put out by the White House talks about the reforms it thinks necessary 'before the organization can be trusted again'. 

This rather implies that the US wants to remain a member of WHO if it can achieve the changes it wants. Whether those changes are feasible is another question — they include holding member states accountable for accurate data-sharing and countering what is referred to as 'China’s outsize influence on the organization'. Trump said the funding halt would last while WHO’s mismanagement of the coronavirus pandemic was investigated, which would take 60-90 days. 

The US is the single largest funder of WHO, providing about 16% of its budget. It provides funds to WHO in two ways. The first is the assessed contribution — the subscription each country pays to be a member. In 2018/19 the US contribution should have been $237 million but, as of January this year it was in arrears by about $200 million.

Much bigger are US voluntary contributions provided to WHO for specified activities amounting in the same period to another $650 million. These are for a wide variety of projects — more than one-quarter goes to polio eradication, but a significant portion also is for WHO’s emergency work. 

The US assessed contribution represents only 4% of WHO’s budget. Losing that would certainly be a blow to WHO but a manageable one. Given the arrears situation it is not certain that the US would have paid any of this in the next three months in any case. 

More serious would be losing the US voluntary contributions which account for about another 12% of WHO’s budget—but whether this could be halted all at once is very unclear. First Congress allocates funds in the US, not the president, raising questions about how a halt could be engineered domestically.

Secondly, US contributions to WHO come from about ten different US government agencies, such as the National Institutes of Health or USAID, each of whom have separate agreements with WHO. Will they be prepared to cut funding for ongoing projects with WHO? And does the US want to disrupt ongoing programmes such as polio eradication and, indeed, emergency response which contribute to saving lives? 

Given the president’s ability to do 180 degree U-turns we shall have to wait and see what will actually happen in the medium term. If it presages the US leaving WHO, this would only facilitate growing Chinese influence in the WHO and other UN bodies. Perhaps in the end wiser advice will be heeded and a viable solution found.

Most of President Trump’s criticisms of WHO do not bear close scrutiny. WHO may have made mistakes — it may have given too much credence to information coming from the Chinese. China has just announced that the death toll in Wuhan was 50% higher than previously revealed. It may have overpraised China’s performance and system, but this was part of a deliberate strategy to secure China’s active collaboration so that it could help other countries learn from China’s experience. 

The chief message from this sorry story is that two countries are using WHO as a pawn in pursuing their respective political agendas which encompass issues well beyond the pandemic. China has been very successful in gaining WHO’s seal of approval, in spite of concerns about events prior to it declaring the problem to the WHO and the world. This, in turn, has invited retaliation from the US. 

When this is over will be the time to learn lessons about what WHO should have done better. But China, the US, and the global community of nations also need to consider their own responsibility in contributing to this terrible unfolding tragedy.

This article was originally published in the British Medical Journal 

On 10 January 2020, Chinese scientists released the sequence of the COVID-19 genome on the internet. This provided the starting gun for scientists around the world to start developing vaccines or therapies. With at least 80 different vaccines in development, many governments are pinning their hopes on a quick solution. However, there are many hurdles to overcome. 

Vaccine development

Firstly, vaccine development is normally a very long process to ensure vaccines are safe and effective before they are used. 

Safety is not a given: a recent dengue vaccine caused heightened disease in vaccinated children when they later were exposed to dengue, while Respiratory Syncytial Virus vaccine caused the same problem. Nor is effectiveness a given. Candidate vaccines that use novel techniques where minute fragments of the viruses’ genetic code are either injected directly into humans or incorporated into a vaccine (as is being pursued, or could be pursued for COVID-19) have higher risks of failure simply because they haven’t worked before. For some vaccines, we know what levels of immunity post-vaccination are likely to be protective. This is not the case for coronavirus. 

Clinical trials will have to be done for efficacy. This is not optional – regulators will need to know extensive testing has taken place before licencing any vaccine. Even if animal tests are done in parallel with early human tests, the remainder of the process is still lengthy. 

There is also great interest in the use of passive immunization, whereby antibodies to SARS-CoV-2 (collected from people who have recovered from infection or laboratory-created) are given to people who are currently ill. Antivirals may prove to be a quicker route than vaccine development, as the testing requirements would be shorter, manufacturing may be easier and only ill people would need to be treated, as opposed to all at-risk individuals being vaccinated.

Vaccine manufacturing

Developers, especially small biotechs, will have to make partnerships with large vaccine manufacturers in order to bring products to market. One notorious bottleneck in vaccine development is getting from proof-of-principle to commercial development: about 95 per cent of vaccines fail at this step. Another bottleneck is at the end of production. The final stages of vaccine production involve detailed testing to ensure that the vaccine meets the necessary criteria and there are always constraints on access to the technologies necessary to finalize the product. Only large vaccine manufacturers have these capacities. There is a graveyard of failed vaccine candidates that have not managed to pass through this development and manufacturing process.

Another consideration is adverse or unintended consequences. Highly specialized scientists may have to defer their work on other new vaccines to work on COVID-19 products and production of existing products may have to be set aside, raising the possibility of shortages of other essential vaccines. 

Cost is another challenge. Vaccines for industrialized markets can be very lucrative for pharmaceutical companies, but many countries have price caps on vaccines. Important lessons have been learned from the 2009 H1N1 flu pandemic when industrialized countries took all the vaccines first. Supplies were made available to lower-income countries at a lower price but this was much later in the evolution of the pandemic. For the recent Ebola outbreaks, vaccines were made available at low or no cost. 

Geopolitics may also play a role. Should countries that manufacture a vaccine share it widely with other countries or prioritize their own populations first? It has been reported that President Trump attempted to purchase CureVac, a German company with a candidate vaccine.  There are certainly precedents for countries prioritizing their own populations. With H1N1 flu in 2009, the Australian Government required a vaccine company to meet the needs of the Australian population first. 

Vaccine distribution

Global leadership and a coordinated and coherent response will be needed to ensure that any vaccine is distributed equitably. There have been recent calls for a G20 on health, but existing global bodies such as the Coalition for Epidemic Preparedness Innovations (CEPI) and GAVI are working on vaccines and worldwide access to them. Any new bodies should seek to boost funding for these entities so they can ensure products reach the most disadvantaged. 

While countries that cannot afford vaccines may be priced out of markets, access for poor, vulnerable or marginalized peoples, whether in developed or developing countries, is of concern. Developing countries are at particular risk from the impacts of COVID-19. People living in conflict-affected and fragile states – whether they are refugees or asylum seekers, internally displaced or stateless, or in detention facilities – are at especially high risk of devastating impacts. 

Mature economies will also face challenges. Equitable access to COVID-19 vaccine will be challenging where inequalities and unequal access to essential services have been compromised within some political systems. 

The need for global leadership 

There is an urgent need for international coordination on COVID-19 vaccines. While the WHO provides technical support and UNICEF acts as a procurement agency, responding to coronavirus needs clarity of global leadership that arches over national interests and is capable of mobilizing resources at a time when economies are facing painful recessions. We see vaccines as a salvation but remain ill-equipped to accelerate their development.

While everyone hopes for rapid availability of safe, effective and affordable vaccines that will be produced in sufficient quantities to meet everyone’s needs, realistically, we face huge hurdles.