United States Department of Global Health

Washington, DC 20099

ACTION MEMORANDUM

To: Secretary of Health and Human Services Mike Leavitt

From: Scott Barrett

Subject: Leveraging the New International Health Regulations

Date: November 1, 2006

When the newly revised International Health Regulations (IHR) enter into force this June, the world will be safer from infectious disease outbreaks. The new IHR represent an important advance in global health policy. They do not, however, go far enough. HHS should lead the U.S. government, and the U.S. government should lead the world, in leveraging the revised IHR to provide even more protection from pandemics. This memo describes the threat and explains what should be done about it.

Background

One year ago, the world stood in fear that the H5N1 bird flu strain would mutate to allow human-to-human transmission capable of killing as many people as has HIV/AIDS, or more, though in a much shorter time. Many casual observers are under the impression that the absence of a major outbreak in the winter of 2005–06 means that the world can now rest easy, that the danger has passed. This is not so: That H5N1 has not turned into a mass global killer does not mean that it may not still do so. More importantly, other sources of pandemic influenza will emerge in the future, as will entirely new diseases.

The 2002 outbreak of Severe Acute Respiratory Syndrome (SARS) showed how easy it is for a new disease to spread in today’s globalized world. A single infected person staying at a hotel in Hong Kong transmitted SARS to at least 16 other guests and visitors, all linked to the same hotel floor, and these persons in turn carried the disease on their travels to Canada, Singapore and Vietnam. Subsequent waves of transmission spread the disease to thirty other countries. Only 916 people died from SARS, but that was due to the self-limiting nature of the disease as much as to the measures taken to contain it. A new pandemic flu strain could kill 100 million people or more: The H5N1 virus has a very high fatality rate and the world’s population is much greater and much more integrated today than it was in 1918, when more than twenty million died from the flu.

We must also contemplate the risk of deliberate release of a biological agent. Terrorists could easily again get hold of anthrax, and they may have already acquired samples of smallpox. Given time, they may be able to develop designer pathogens (perhaps crossing the virulence of Ebola with the infectiousness of measles). Polio has already been synthesized.

Clearly, there are dire and growing threats to global health, and the world is not well enough prepared to deal with them. As you know, the United States and other governments are addressing these threats, but steps taken so far have been mainly unilateral and defensive; they need to be global and offensive. We therefore need to fundamentally change our perspective to address the threat of emerging infectious diseases. Urgent and sustained action is needed in five areas: prevention, preparedness, surveillance, reporting and response.

Prevention

The human form of Bovine Spongiform Encephalopathy (BSE), or variant Creutzfeldt-Jakob disease (vCJD) known as “Mad Cow” disease, arose in the United Kingdom because of the practice of using cattle offal, including brain and spinal cord tissue, to feed other cattle. Were it not for this rendering process, the original prion mutation–that is, a change in the structure of infectious particles of protein–would not have spread so widely.

Could this risk have been foreseen? Probably not. But diseases that develop from mutations of already-recognized agents can be foreseen–and prevented. The anti-malarial drug, chloroquine, for example, has lost its effectiveness. Overuse of this drug allowed evolution to select mutations that resist chloroquine, and these new mutations have now spread around the world. Unless decisive action is taken, resistance to the new, artemisinin-based anti-malarials will also develop.

To prevent this, we need to set global minimum standards. Monotherapy versions of the new anti-malarials should be banned. Combination therapies, by contrast, should be subsidized. Currently, neither action is being taken. The World Health Organization has threatened to “name and shame” companies that manufacture and distribute the monotherapies, but that is a weak response. Meanwhile, donor countries have failed to subsidize the new combination therapies, still seeing development as requiring investments in particular states rather than as a broader challenge with ecological and health-related aspects. Chloroquine resistance developed independently in Southeast Asia and South America, then spread to Africa where the falciparum form of malaria now kills between one and two million children each year. It is the nation-centric view of development that has failed to prevent this disaster.

We must also act to reduce the risk of an H5N1 mutation that would allow human-to-human transmission. A new mutation could arise from wild migratory birds infecting domesticated fowl, these animals then passing it to humans, and infected humans in turn transmitting the disease to others around the world. Standards that might prevent or make less likely this chain of events do not now exist at the international level. (Indeed, even the European Union has taken a fragmented approach to this current challenge.)

Establishing standards is essential, but so is enforcement. In June 2005 reports surfaced that farmers in China had used an anti-viral drug, amantadine, to suppress major bird flu outbreaks in violation of international livestock guidelines. The consequence is that the H5N1 virus has now become resistant to this drug, so other countries relying on it (mainly poorer countries) must now use more expensive anti-virals for treating humans.

To sum up, the challenge of emerging infectious diseases requires collectively agreed to, minimum global standards, coupled with assistance to give all governments the necessary capacity to enforce those standards.

Preparedness

Prevention is not always possible and may be inadequate. We must therefore be prepared to deal with new outbreaks. Preparedness is in every country’s self-interest, but it also yields global benefits because preparedness can help limit spread.

Many countries are now stockpiling anti-viral drugs and investing in the development of vaccines that, we hope, will be effective against an H5N1 mutation. These measures are to be welcomed, but not every country can afford them–and countries that do not invest in preparedness raise risks to other nations. It may not be possible to prevent spread, but even slowing down transmission will buy the precious time needed to develop better tools with which to fight a new influenza strain (our tools today only guess at the nature of the strain likely to emerge).

Suppose a new pandemic strain emerges in a developing country that lacks the drugs and vaccines to slow its spread. Will countries with stockpiles use them to prevent the spread of the disease at its source, or instead use them defensively to protect their own populations? If stocks are used at the source of an outbreak, they will more effectively slow global spread. But that would expose the donating country to a sizable risk. Stocks are limited and must be rationed, so it is not now possible for countries to do both.

This is an unacceptable circumstance, so an adequate global stockpile is needed. A global stockpile does exist (donated by the manufacturer of the anti-viral drug oseltamivir), but it can treat only three million people. By contrast, the United Kingdom, an island nation with a population of sixty million, has a stockpile of almost 15 million doses. What happens if a new bird flu epidemic emerges in Mumbai, with a population of nearly twenty million, in a country without its own stockpile?

We also need to invest in vaccine production capacity. Current capacity is very limited and located in just a few countries. Should there be an outbreak, where will scarce vaccine stocks be deployed? In the countries where production capacity is based, or where deployment would deliver the greatest global benefit? Having more capacity distributed in more places, and rules for distributing limited supplies globally, will ease this sort of dilemma greatly.

To summarize: Global preparedness requires major investment in the tools that can prevent spread at the source of an outbreak, wherever that may be.

Surveillance

Surveillance is needed to identify outbreaks of new diseases. Only when the Centers for Disease Control and Prevention in the United States noticed an unusual increase in the demand for pentamidine, a drug used to treat a rare lung infection, was the HIV/AIDS epidemic first identified in 1981. Far from being a success, however, this discovery showed how inadequate global surveillance really was. We now know that HIV/AIDS first emerged on a different continent about fifty years before it was identified in San Francisco.

Surveillance capacity is weakest in developing countries, and failed and fragile states are the biggest challenge. The world is devoting an unprecedented amount of attention today to poliomyelitis because of the ongoing initiative to eradicate the disease, and yet surveillance has been inadequate. New cases of polio were discovered in Sudan in 2004, three years after officials declared its elimination. Subsequent analysis showed that the disease had remained endemic in the country all that time. If a disease we are looking for cannot be identified, what are the chances we will notice the outbreak of a disease that we do not even know exists?

Surveillance is also inadequate in rich countries. For example, an avian influenza virus (subtype H7N7) circulated undetected in the Dutch poultry industry for several months before a major outbreak occurred in 2003. Detection of BSE in the United Kingdom also took longer than it should have. According to the BSE Inquiry, farmers failed to refer BSE cases to authorities in the early stage of the epidemic for fear that the discovery would harm them financially.

Investment for improving surveillance should focus on developing countries, where capacity is weakest and where conditions for the emergence of new diseases are ripe. Surveillance must detect small changes in the health of populations, which in turn requires an effective public health infrastructure. Most donor aid for health goes to “vertical programs” targeting particular interventions. Surveillance requires a broader investment in capacity.

Reporting

Surveillance is of greatest benefit when new disease outbreaks occur, but only when surveillance is combined with reporting can countries protect their populations and help prevent disease from spreading globally. Unfortunately, perverse incentives work against effective reporting. Countries that report new outbreaks are typically “rewarded” by being made the targets of trade restrictions. Discovery of a single case of BSE, for example, routinely triggers a wholesale ban on beef imports from the reporting country–a restriction that can last a very long time.

The problem of reporting was dramatically and alarmingly demonstrated by the SARS outbreak. The World Health Organization (WHO) first learned of a serious outbreak from unofficial sources, transmitted electronically and linked to its Global Outbreak Alert and Response Network. It was only the day after this happened–a full three months after the epidemic started–that the Chinese government reported the SARS outbreak.

Despite this failure, the SARS experience teaches that reporting is no longer as serious a problem as it once was. The availability of information from unofficial sources, coupled with the WHO’s willingness to act on such information, means that countries today gain little by hiding what they know, and lose big when their attempts at concealment are exposed. The SARS experience has helped to establish a very positive new norm: the duty to report.

Response

The incentives to prevent epidemic disease at its source are strong, but the opportunity to do this depends on preparedness, surveillance and reporting. Yet these three areas are the weakest links in the global system for addressing emerging infectious disease threats today. This remains the case despite improved IHR scheduled to enter into force in May 2007.

The revised IHR do contain three critical improvements. First, they require notification of all events that may “constitute a public health emergency of international concern”, including new diseases as well as outbreaks of the three diseases listed in the current IHR. Second, the revisions make reporting more reliable by allowing the WHO to act on the basis of unofficial sources of information and by obligating countries to report outbreaks arising outside their territories. Third, the revisions require that any trade-related health measures adopted unilaterally be neither “more restrictive of international traffic” nor “more invasive or intrusive to persons than reasonably available alternatives that would achieve the appropriate level of health protection.” Such measures must also be based on “scientific principles” and “available scientific evidence of a risk to human health.” These measures make the revised IHR compatible with the WTO.

While these changes are welcome, they do little to address the fundamental weaknesses in the current system. The revisions do not and cannot provide the poorest countries with the means to deliver on their obligations to detect, notify and report on disease outbreaks. The IHR revisions also fail to create new incentives for countries to build a fully global surveillance and response capacity. Finally, the IHR revisions seek to address outbreaks, but not the conditions giving rise to them–poor sanitation, nutritional and food safety deficiencies, and the absence of minimum standards to prevent resistant strains and dangerous mutations from emerging and spreading.

The Need for a Global Response

The U.S. Institute of Medicine has put it well: “Infectious diseases are a global threat and therefore require a global response. . . . The United States’ capacity to respond to microbial threats must therefore include a significant investment in the capacity of developing countries to monitor and address microbial threats as they arise.”¹ HHS must act vigorously and urgently to bring about such investment. Only if the U.S. government leads the way will other countries join in financing this investment in capacity.

How should we proceed? We should take advantage of the revised International Health Regulations. The new IHR offer the goal of minimum global standards for surveillance, but do not specify the technical inputs required to meet this goal or suggest a platform for the financing essential to it. We must provide these missing links.

There is a precedent for how to do this: The 1990 amendment to the Montreal Protocol on phasing out ozone-depleting substances established procedures by which technical requirements could be agreed upon and then financed by the industrialized countries. This agreement has worked: The ozone layer is expected to recover by around 2050. A similar agreement is needed now to address the threat of emerging infectious diseases. Mr. Secretary, it is in our interest that it succeed, and HHS must lead the way.

cc: Director CDC; SECSTATE, SECCOM

1.
Mark S. Smolinski, Margaret A. Hamburg and Joshua Lederberg, eds., Microbial Threats to Health: Emergence, Detection, and Response (National Academies Press, 2003), p. 8. Emphasis added.