Emerging Infections in Europe
The realization of the “global village” is most evident in Europe, as barriers to travel, commerce, and information sharing among countries are removed. However, Europe is not one country, and many of the states that comprised the former Soviet Union are actually located in central Asia. A challenge for Europe lies in how best to integrate local needs with national, political, and international needs when it comes to disease surveillance and response. The need for a clearer understanding of local requirements and the need for leadership behind the issues, followed by critical assessment and strategic planning for infrastructure development for infectious disease surveillance and response systems, are as evident in Europe as elsewhere. Yet, legal barriers or legal implications for building or implementation of such disease surveillance systems abound. Some countries may believe that these efforts could undermine their ability to protect the health of their citizenry or to retain state sovereignty. Some countries may be concerned about the diminishment of state authority within their own territories. International and national laws must be understood and discussed in the context of establishing cooperative efforts and meeting local needs for strategic planning in terms of infectious diseases. The Europe-wide EntreNet is one example of cooperation and coordination across political and geographical boundaries for the prevention and control of human salmonellosis and other food-borne illnesses in Europe.
PANDEMIC STRATEGIC PLANNING
Jane Leese, M.D.
Senior Medical Officer, Immunization Team Department of Health, London
The Institute of Medicine (1992) defined emerging and reemerging infectious diseases as those “diseases of infectious origin whose incidence in humans has increased within the past two decades, or threatens to increase in the near future.” This definition is wide, encompassing not only new entities, but also new incidents or outbreaks of established diseases with public health implications, changing trends, and diseases that have increased in importance because of, for example, the actual or potential emergence of antimicrobial resistance.
Diseases appear on the national or international political agenda for a variety of reasons: (1) new scientific evaluations clearly demonstrate a risk or potential risk to public health (this may not, however, be enough on its own); (2) a sudden, rather than an insidious, onset of an infectious disease; (3) preconceived perceptions of a disease (e.g., the outbreak of plague in India in 1994 was associated with international hysteria out of proportion to the risk on the basis of preconceived notions of the Black Death and other historical incidents); (4) a risk to trade or tourism; (5) extensive media coverage; (6) powerful lobbies at work; or (7) the issuance of an authoritative report from a respected body. A variety of reasons then affect how long a disease stays on the agenda, many of which are not necessarily scientifically or clinically appropriate. Another influence is cost. For example, in the United Kingdom a report from the National Audit Office on the cost to the National Health Service of hospital-acquired infections is likely to focus action on such infections as a developing priority.
Pandemic Influenza Contingency Plan in the United Kingdom
The study of influenza has provided useful experience in planning for an emerging infectious disease. In the United Kingdom it has been estimated that some 3,000 to 4,000 people die from influenza every year. In 1989, the most severe of recent epidemics, it was estimated that 26,000 people died from an influenza-related illness during the 6 to 8 weeks of the epidemic. Drawing on the experience and on experiences with previous pandemics of the last century, the United Kingdom has developed a national pandemic influenza contingency plan. The plan defines the roles and responsibilities of all the organizations and people who would be involved in the response to a new pandemic. What first emerges from this exercise is the large number of people who would be involved in the response and therefore the need for strong coordination.
The plan moves in phases, from the interpandemic period, through recognition of a new strain with pandemic potential, to outbreaks of illness outside the United Kingdom, outbreaks within the United Kingdom, the pandemic stage
itself, and then the end of the pandemic, when the whole response would be reviewed. The World Health Organization (WHO) has since published guidance on planning for a pandemic. Currently, the effort is to bring the plan for the United Kingdom into concordance with the WHO plan.
There are five important and parallel strategies within the plan for the United Kingdom. The first concerns surveillance so that the country is in the best position to identify new strains of influenza and monitor their geographic spread. The second concerns vaccine development and supply and the development and implementation of vaccination policies. The third strategy concerns communications plans. The fourth concerns managing the burden of disease when it arises and the accompanying disruption to health and other services, and the fifth component is research.
The Hong Kong Influenza A Virus Outbreak
The outbreak of avian influenza A virus subtype H5N1 in Hong Kong in 1997 put the plan for the United Kingdom to its most recent test. The speed at which the outbreak became widely publicly reported led to some initial confusion about its nature and the size of the geographical area through which it was spreading, emphasizing the importance of a strong communications strategy. The United Kingdom was fortunate in that the WHO laboratory based in London was able to provide authoritative information during these early stages. Critical also was the high level of organization in Hong Kong, including the timely establishment of a website, updated at a specified time daily. Within the United Kingdom another early issue was whether surveillance was sufficient to detect cases in the United Kingdom should they be imported. General practitioners in areas of the country with large Chinese populations were asked to be alert to new cases of influenza-like illness and to send samples for investigation.
Another early part of the response was establishment of laboratory facilities suitable for work on the virus and the development of reagents. One problem not anticipated in the plan for the United Kingdom was that the Hong Kong virus was of avian origin. Thus, the Ministry of Agriculture needed to be involved and was rightly concerned about both the importation of the virus and proper containment in the laboratories handling it. The laboratories had to increase their containment facilities. Occupational health policy was a further consideration: should staff working on the virus take amantadine prophylactically? Another early issue to be considered was whether assistance should be sent to Hong Kong. This extended to how Europe might in the future better support WHO in its response to international outbreaks.
One lesson from this incident was that vaccine production during a pandemic may present unforeseen complexities and take longer than planned. On this occasion, the virus was so virulent that it killed the ferrets in which it was inoculated as well as the eggs in which it was to grow. One possible vaccine
strain was identified, but it was still highly virulent and could not be grown under usual manufacturing conditions. A government-funded laboratory with suitable containment facilities was employed to produce a batch of virus to make sufficient vaccine for early clinical trials. This would have presented problems had manufacture on a large scale been required.
European Response to Emerging Infectious Diseases
Within Europe, considerable progress has been made in recent years to improve preparedness and the response to emerging infectious diseases. In September 1998, the European Parliament and Council passed a decision to set up a network for the epidemiological surveillance and control of communicable diseases in the community. This effort, which became active in July 1999, required the linking of national surveillance centers as well as administrations responsible for public health. The system builds on an established set of networks for surveillance of individual diseases, such as travel-related Legionnaires' disease, EntreNet (for enteric organisms), human immunodeficiency virus infection (HIV)/AIDS, tuberculosis, and drug resistance. Additional work has been undertaken to underpin the network. National surveillance institutes have collaborated in looking at standards and priorities for surveillance. A highly successful field epidemiology training program, called the European Programme for Intervention Epidemiology Training (EPIET), has been established. This has not only provided a cadre of people with expertise in handling international incidents, but has also facilitated international collaborations through regular contacts among EPIET instructors and trainees.
Regular surveillance bulletins in both paper and electronic form, have been produced. In addition, inventories of the available capacities and capabilities across Europe have been generated.
One important component of this new network is that it puts the public health authorities, usually the ministries of health, in communication with each other. The first priority for this part of the network has been to set up an early-warning system, whereby secure messages are shared as soon as a potential problem arises. In the long term, greater discussion over appropriate control measures will also be required of the network, although these measures remain the responsibility of individual member states.
Importance of Local Surveillance and Collaboration
Although cross-national cooperation is important, its success depends on the quality of local surveillance. In early-warning and response systems, the local level is required to serve a disease intelligence function and needs the ability to assess possible indicator events (e.g., changes in over-the-counter drug sales at pharmacies, school absenteeism, as well as the data generated from more conventional disease surveillance activities). Many emerging infections are zoo-
notic in origin. Surveillance systems at the local level must thus work closely with agricultural and veterinary colleagues and those undertaking surveillance in other related fields. Surveillance systems must be flexible to adapt, for example, to changing patterns of health care. The trend, for example, towards the use of near-patient diagnosis or the use of advice lines instead of a visit to a general practitioner 's office could result in the loss of valuable surveillance data unless the new systems are adapted to the activities required for infectious disease surveillance. All surveillance increasingly needs to be undertaken with due attention to protection of patient confidentiality and privacy. If preparedness for emerging infectious diseases is to be maintained, surveillance systems need to be reviewed and adapted at regular intervals at the local, national, and international levels.
A VIEW FROM THE GROUND: TUBERCULOSIS AS AN EXAMPLE OF A REEMERGING INFECTIOUS DISEASE IN THE FORMER SOVIET UNION
Ian Small, M.A.
Head of Mission, Médecins sans Frontières, Tashkent, Uzbekistan
In the aftermath of the Cold War, a diverse group of 15 independent countries—with a population of more than 350 million people, dozens of different languages, and just as many different ethnic and national groups—faced the reemergence of the tuberculosis (TB) bacillus. TB stands above all emerging infections as the single largest public health concern in the region. Various factors affect the response to this threat, including economic, environmental, and political elements, the infrastructure and the capacity of the stricken communities to respond, diagnostic and treatment considerations and constraints, and the role of nongovernmental organizations (NGOs) in combating TB.
This summary focuses on the situation in five Central Asian states that were part of the former Soviet Union (FSU)—Kazakhstan, Uzbekistan, Kyrgyzstan, Turkmenistan, and Tajikistan—with a particular focus on the 5 million people living in what is considered the world's greatest environmental disaster area, the Aral Sea area. Reference is also made to the high rate of TB in Russian prisons.
With the drastic economic, political, and environmental changes in the landscape of the FSU came a change in disease patterns in the last decade of the 20th century. Diseases that were well controlled, well hidden, or simply not prevalent during the Soviet period began to appear. The recent development of
an HIV/AIDS epidemic in the Slavic states is an ominous precursor to similar developments in the Caucasus and Central Asia in the near future. From the start of the outbreak in Russia in 1987 until 1995, the total number of HIV-positive individuals officially registered was relatively small. During 1996 alone, however, 1,495 new infections were officially registered. In 1997, 4,337 new infections were registered of which 3,200 were among intravenous drug users. By the end of 1998, the total number of persons officially registered was more than 10,000, and by June 1999, the total had climbed to more than 14,000.
Because of possible inaccuracies in counting, however, it is possible that at the end of 1999 there are 100,000 to 200,000 persons with HIV in Russia alone. The socioeconomic upheaval in Russia and other countries of the FSU has seriously hampered the health system's ability to respond to this epidemic. The health system is overburdened and severely underfunded, resulting in material shortages and the nonpayment of salaries. Years of isolation from international research on HIV/AIDS, concomitant with the stigma associated with the disease, contributed to a basic lack of HIV/AIDS knowledge among health workers and the public.
The incidence of diphtheria has also skyrocketed in recent years. In 1980, the region accounted for less than 1 percent of diphtheria cases worldwide. By 1994, almost 90 percent of reported cases were occurring in the region, with more than 50,000 cases reported in 1995.
The incidence of malaria, which had been all but eradicated in the FSU, in the last few years has shown an alarming increase in the most southern states— from a few incidental and most likely imported cases of malaria in Tajikistan in the early 1990s, to almost 20,000 cases reported in 1998. In a region with a vast amount of stagnant water because of ineffective irrigation schemes and an entire generation of people with no experience with malaria prevention, a public health crisis is in the making as the malaria belt moves north.
It is TB, however, that typifies the threat that reemerging diseases can have on the FSU. The TB incidence rates in the FSU vary from country to country, with rates of anywhere from 50 per 100,000 population in Russia to a high of 300 per 100,000 population in the Aral Sea area of Central Asia. This represents more then a doubling of cases in less than 7 years. The prison population has an incidence 60 to 100 times higher than that among the civilian population. The uniqueness of the problem lies in the proportion of multidrug-resistant TB (MDR-TB) cases in civilian society, which is roughly 5 to 10 percent of all cases, and in the prison setting, where at least 20 percent of all patients have MDR-TB. These high rates of MDR-TB, in contrast to the rates in other regions of the world, reflect the breakdown of the political, economic, and health infrastructures in the region.
The Soviet Union had a very effective, albeit unsustainable, TB prevention and control infrastructure. With the break-up of the Soviet Union, however, the ensuing economic collapse, and the redirection of political priorities, the TB prevention infrastructure fell apart. The governments of the region and health care workers showed reluctance to adopt the WHO-developed directly observed treatment (short course) strategy (DOTS). In several countries, the old Soviet law, which outlawed the reporting and even the use of the word “epidemic,” is still in the minds of health workers and politicians, even though it is not on the books. Such attitudes have slowed the reform of the TB prevention and control infrastructure.
Regional and other governments have shown a dangerous disregard for TB. TB is a disease that is either treated well, or not at all. The effect of the remnants of the old TB program is the development of MDR-TB. The drugs required to treat pansensitive TB cost roughly $15 to $40. The costs of drugs used to treat MDR-TB are 250 times more, and even then, cure rates reach only 50 percent. It has been estimated that $600 million would be required to cover 70 percent of the world TB cases with DOTS. Total international aid for TB in 1997 was a paltry $16 million. At present, however, MDR-TB has increased the transnational public health threat, and the costs associated with combating the disease cannot be met locally.
Directly associated with the economic collapse and the lack of political commitment is a long list of forces at play, and these are driving the TB epidemic in the FSU. They include the following:
Lack of surveillance, monitoring, and program evaluation. The only way a reliable rate of TB can be determined is with a rigorous TB control program in place. This presents a paradox: the stronger the TB control program, the greater the chances that the incidence of TB is insignificant. Conversely, the time when monitoring is of utmost importance is precisely the time when epidemiological surveillance capacity is likely to be poor. Moreover, in the FSU an accurate denominator cannot be determined to arrive at an incidence rate because a census has not been taken since 1989 and millions of people have migrated throughout the region.
Slowness in adapting new and effective protocols, such as DOTS. As of June 1998, within the five Central Asian countries, less than 2 percent of the estimated 50 million people were surveyed by DOTS. The longer this occurs, the greater the amplification of TB drug resistance, leading to the development of MDR-TB when DOTS is no longer effective. In addition, how likely is it that countries that have been slow in adopting DOTS will refer to DOTS Plus, a second-line drug treatment regimen for MDR-TB?
Lack of drugs. The countries of Central Asia are not in a position to finance the three- to four-drug regimen associated with a DOTS program, let alone consider adding second-line drugs for the treatment of MDR-TB.
Poor laboratory quality. The Soviet TB treatment protocol had an overreliance on X-rays for the diagnosis of TB, in contrast to a DOTS program, which primarily relies on sputum smear microscopy for the diagnosis of TB. Most laboratories that were once equipped with such diagnostic tools were underused and are now almost in a state of complete collapse, lacking even basic reagents. In all of Central Asia, it is safe to say that not one laboratory has the capacity to conduct culture and drug sensitivity testing for the 50 million people in the region, with a scarce few laboratories that can even perform simple diagnostic tests.
Deteriorating physical infrastructure and logistics management. A cornerstone of the centralized economy in the FSU was the assignment of productive enterprises to various regions. When the FSU collapsed, the entire logistics chain broke as well. As a result, health care resources and logistics in Central Asia have been overlooked. It is common that facilities are not able to separate the infectious from the noninfectious patients, let alone provide a minimum level of hygiene. Moreover, the buildings are often cold during winter months and are dark and unventilated, providing an environment conducive to the spread of the disease.
Lack of trained health workers. There is a generalized myth about an abundant supply of health practitioners in the FSU. Indeed, during the Soviet era, health care workers were numerous and well trained. In the Aral Sea area, not only has there been a significant exodus of trained staff because of the environmental disaster, placing a huge strain on the capacity of the health system, but the majority of health care workers who have remained in the region are nearing retirement and have had little to no upgrading of their skills. Given an average monthly salary of roughly $20, it is not surprising that few young people are entering the medical system, let alone dedicating their lives to TB—often literally, given nonexistent staff safety measures.
Lack of financing and misdirected priorities. A cost-effectiveness study in Uzbekistan that compared the economic treatment costs of the traditional Soviet TB protocol and DOTS showed that if the government implemented DOTS, a savings of $5 million per year would be incurred. Once the epidemic was under control, the savings would continue to increase because of the immediate decrease in prevalence and the gradual decrease in incidence. Yet, there is still reliance on expensive mass screening programs using radiology.
Forty-two percent of all TB cases in Russia are among members of the prison population. Little is known about the prisoner infection rate in Central
Asia, but it is likely to be similar to, if not worse than that in Russia. Metaphorically, the Russian prison system is a petri dish that cultures various strains of the TB bacillus. Every year the system incarcerates 300,000 otherwise healthy Russians and releases another 300,000, most of whom will have been exposed to TB during their incarcerations. Among them, approximately 10 percent develop active disease and 80 percent carry the TB bacterium in a latent state; approximately 40 percent of all patients are exposed to MDR strains. The cause of high levels of drug resistance is the delay in the implementation of DOTS and the lack of prison reform. The crisis is almost at the point at which, unless second-line drugs are introduced in the prison system, the situation will never be controlled.
To date few organizations have been active in TB control activities. NGOs can play a progressive role in this area by being proximate to the problem and, through advocacy, ensuring that the issue is placed on local, national, and international agendas. NGOs can develop pilot programs, conduct assessments, provide training, and contribute to the wider implementation of DOTS. NGO advocacy can be as straightforward and uncomplicated as the promotion of TB as a serious public health threat and DOTS as an effective way to control it. But without access to affordable and essential quality drugs and sustained financing, however, little progress can be made, particularly concerning MDR-TB.
NGOs can also advocate for increased activity in the private sector. Of the 1,233 drugs licensed worldwide between 1975 and 1997, only 13 were for tropical diseases and TB. Of those, two were slight modifications of existing drugs, two were produced for the U.S. military, and five were the outcomes of veterinary research. Drug companies, which spent a total of $40 billion on research in 1999, in two decades have developed only four medicines specifically for tropical diseases.
If NGOs become involved in the implementation of DOTS-based programs, they must be prepared to do it for the long run. It is unethical to enter a country, take away the country's existing tools for controlling TB (which are not fundamentally wrong, just inefficient and unsustainable), and leave before new methods have taken hold.
Pilot programs should balance the short-term objective of TB control in a specific area versus the long-term goal of complete DOTS coverage. Pilot programs should aim to develop momentum by reducing community stigmatization of TB, gaining patient and health worker confidence, and obtaining political commitment. Implementation of pilot programs is not the same as further extension of program coverage. The word “pilot” should not be used as a poor excuse for not wanting to accept responsibility for what happens next. Pilot programs should be monitored by using a set of assessment criteria to set the course for the full coverage of DOTS. These “DOTS-for-ALL” assess the following:
documentation and the evaluation of the pilot phase and lessons learned,
laboratory capacity and quality,
reliability and availability of epidemiological data,
whether donor and financial commitments are sustainable, and
Although this discussion has concentrated particularly on TB as an example of an emerging and reemerging infectious disease, it highlights multiple concerns that apply equally to other infectious diseases in the FSU and surrounding regions. Nevertheless, TB exhibits several characteristics that make it one of the single largest health burdens in the region.
EUROPEAN RESPONSES TO EMERGING INFECTIONS AND THEIR POLICY IMPLICATIONS
Julius Weinberg, M.D.
Pro-Vice Chancellor (Research), School of Informatics, City University, London, and Honorary Consultant Epidemiologist, Public Health Laboratory Service, Communicable Disease Surveillance Centre, London
It is important when setting priorities for control of emerging and reemerging infectious diseases that one does not lose sight of the importance of controlling diseases that persist, for example, acute respiratory infection in children in the developing world.
The European Union (EU) has changed the environment for public health issues by creating a multinational geographical area within which people and goods move freely and by providing funds and the opportunity to share information so that an appropriate supranational response can be made. Although Europe does not face the same types of infectious disease problems found in Asia, Africa, and Latin America, it has a unique set of issues to contend with in the area of infectious diseases. For example, WHO has had to assist the countries of Central and Eastern Europe with the rebuilding of their communicable disease surveillance activities. The collapse of the previous regimes, military conflict, and the breakdown of public health measures has led to the recrudescence of some old problem diseases, in particular, diphtheria and TB, and has also led to anxieties about other diseases (e.g., typhus).
The movement of people around Europe has been associated with problems such as the resurgence of syphilis in Finland, importations of resistant TB into
many countries, importation of resistant pneumococcus from Spain to Iceland, and the encroaching HIV/AIDS epidemic. The EU response has been to develop networks around specific agents, such as Legionella and Salmonella. The networks have facilitated rapid communication and response. For example, an outbreak of salmonella in the United Kingdom led to the identification of contaminated batches of a children's snack in several other European countries and the United States. Several outbreaks of legionellosis, which may not otherwise have been recognized, have been identified and controlled as a result of the timely pooling of data from a number of countries.
Antimicrobial resistance cannot be dealt with at the national level; it requires international collaboration. The European Antimicrobial Resistance Surveillance System (EARSS) is being developed. This will facilitate the sharing of methodology and data. As resistant organisms do not respect national boundaries, there will need to be collaboration of national and international efforts against resistance.
In addition to the disease- and organism-based networks, a number of infrastructure-related collaborations have been developed. The European Programme for Intervention Epidemiology Training (EPIET), which involves several EU countries in core training and exchanges, may provide the EU with the nucleus of a European system of trained and trainee epidemiologists who can provide support during international outbreaks. Other infrastructure developments include informatics programs and Worldwide web-based databases that will soon provide important information on laboratories within Europe that have the capacity to support and assist with investigations of certain outbreaks.
Critical aspects of international collaborations are establishing trust and harmonizing epidemiological and laboratory practices. One of the great successes of EntreNet, a network established to improve the prevention and control of human salmonellosis and other food-borne infections in European Union countries, has been the development of a Europe-wide typing system for Salmonella enterica serovar Enteritidis, a process that has resulted in the development of trust, collaboration, and exchange of materials. Conflicts can arise, however, around jurisdictions, costs, and international politics. Furthermore, countries have different traditions of accountability and data dissemination that must be acknowledged and considered. In addition, there may be conflicts with international agencies, such as the WHO, and with NGOs. The potential for disagreement must be recognized and dealt with early.
An important consideration in international collaborations is that national work always comes first, which can sometimes cause tensions and strains on resources, especially for smaller countries. On the positive side, collaborations can result in the sharing of good ideas. For example, in the United Kingdom a public education campaign that uses the character “Andy Biotic” aims to inform the general public about inappropriate antibiotic use. Similar campaigns are ongoing in Ireland and Sweden.
To develop consensus across diverse nationalities, a Delphi exercise was used to develop a plan on communicable disease surveillance at the European level. The plan was based on completion of a priority ranking of topics for collaboration by using the knowledge and experience of national experts in a consensus method adapted from the Delphi technique. By this technique, consensus is reached by means of questionnaires and feedback rounds circulated among a group of experts. The method retains anonymity and avoids the drawbacks of committee settings, such as domination or coalition. The exercise also tapped people 's opinions about important mechanisms for collaboration, such as information exchange for early warnings and early detection through the pooling of data.
Such ranking exercises would yield different results in different regions of the world or if, for example, the global burden of disease were a primary consideration. However, they have value in developing consensus and in generating outputs that can be used to plan future programs. For example, a list of priorities was submitted as expert advice to the European Commission. Influenza was identified as a high priority for international surveillance, as was acute poliomyelitis, antimicrobial resistance, and cholera.