Dangerous Pathogens 2000: an overview of the international conference
Smith The Medical School, University of Edgbaston, Birmingham B15 2TT, Uk.
1. Introduction, 621
2. The problems of coping with infectious disease, 621
2.1. The rapid evolution of micro-organisms, 621
2.2. Animal reservoirs, 621
2.3. Increased travel, 621
2.4. Changes in human behaviour, 622
2.5. Poverty leading to poor public health infrastructure, 622
3. Reasons why infectious disease will not win, 622
3.1. The survival record in past epidemics, 622
3.2. The effectiveness of public health measures, 622
3.3. The strength of the natural defences, 622
3.4. Present availability of drugs and vaccines and improvements in patient care, 623
3.5. The impact of new knowledge, 623
4. Conclusion, 623
The conference was wide ranging. It dealt with nine bacterial, 10 viral and two rickettsial diseases, malaria and a fungal disease. In addition, there were sessions on genomics and on therapeutics. It is impossible to summarize this myriad of subjects. I have confined myself to making some comments on the general theme of the conference, taking into account relevant points made by some of the speakers. The aim of the conference was set down on the first page of the book of abstracts. ‘At the beginning of the new millenium infectious disease is still a major scourge of the human race. The aim of this conference is to review the ongoing battle between man and micro-organisms, past, present and future and to identify any gaps in our knowledge that need to be filled to ensure that man comes out on top.’ The downside is described first and then the upside.
2. THE PROBLEMS OF COPING WITH INFECTIOUS DISEASE
2.1. The rapid evolution of micro-organisms
This is the major biological problem. It arises from high mutation rates coupled with rapid multiplication which leads to quick selection. One result is the drug resistance mentioned by D.B. Young for Mycobacterium tuberculosis, by G. Duckworth for Staphylococcus aureus, by J. Wade for enterococci, by D. Carucci for malaria and W. Blattner for HIV. Lateral transfer of virulence genes by phages, plasmids, transposons and pathogenicity islands also contributes to evolution of new types of bacterial pathogens as demonstrated by B.M. Davis for Vibrio cholerae and T. Reed for Bacillus anthracis. For viruses with segmented genomes, reassortment of′ genes between different strains can produce new and potentially more virulent viruses as emphasized by C.W. Potter for influenza virus.
2.2. Animal reservoirs
This danger is always with us. W. Blattner described the probable derivation of HIV from a virus infection of chimpanzees in Africa. G. Lloyd emphasized that human infections with new arenaviruses, hantaviruses and filoviruses will probably emerge from animal and arthropod borne viruses. Birds appear to have been the reservoir for the recent outbreak of West Nile virus infections in humans. Domestic animals are reservoirs for antibiotic resistant food poisoning bacteria such as Salmonella typhimurium and Campylobacter jejuni. P. Beverley for smallpox virus and D. Wood for poliomyelitis virus underlined that lack of an animal reservoir is essential for eradication of human virus diseases.
2.3. Increased travel
This has a dual effect. It provides opportunity for rapid spread of current epidemics as emphasized by D. Stewart-Tull for cholera and G. Lloyd for newly emerging virus diseases. But there are now few virgin populations comparable to those that succumbed in the past to malaria, yellow fever and smallpox.
2.4. Changes in human behaviour
Perhaps the most obvious example is the rise in levels of sexually transmitted diseases due to increased sexual promiscuity. However, changes in human behaviour brought about by poverty, war, population growth, migration and urban decay, may contribute to the emergence of viral and richettsial disease as was pointed out by G. Lloyd and A. Azar, respectively.
2.5. Poverty leading to poor public health infrastructure
Although the microbiological problems are formidable, this is the major barrier to a significant reduction in infectious disease. It occurs in many areas of the world and many speakers have deplored it. The situation means that not only is there more infectious disease in the particular countries concerned but also international surveillance of emerging diseases is severely hampered. The importance of early recognition of such diseases was emphasized by G. Lloyd.
3. REASONS WHY INFECTIOUS DISEASE WILL NOT WIN
3.1. The survival record in past epidemics
The first day of the conference contained excellent descriptions of the ancient scourges of mankind: plague, malaria, cholera, typhus, influenza, syphilis, yellow fever and smallpox. The epidemics killed many people and had serious effects on human affairs. However, many people survived, far more than those who succumbed. Death rates were rarely more than 30%. In the 1918 influenza pandemic 20–50 million people died but hundreds of millions survived. Although heavily handicapped, the human race carried on. Here it should be stressed that these epidemics occurred in Europe and elsewhere at a time when there was poverty, bad housing, undernourishment, few or no public health measures and certainly no vaccines or drugs. These are the conditions which, unfortunately, still exist in many parts of the world. The inference from the past is that even in these areas relatively high survival from infectious disease will occur.
The present scourge is AIDS and, as W. Blattner described, it is devastating in Africa. Other parts of the world may become equally affected. Nevertheless, AIDS has been controlled in richer countries by implementing safer sexual practices and needle exchange schemes, and the effectiveness of antireverse transcriptase drugs and protease inhibitors. The risk of HIV infection being passed from mother to infant has been reduced. There are increasing signs that the richer nations and pharmaceutical firms may help in extending these effective but expensive measures to poorer nations. Also, it was good to hear from W. Blattner that the future development of a vaccine still remains a distinct possibility. Control of AIDS is a long way off but there are signs that it can be achieved.
3.2. The effectiveness of public health measures
Several speakers at the conference, including R. Stanwell-Smith, D. Stewart-Tull, T. Brooks and P. Russell, underlined the effectiveness of simple public health measures in controlling infectious disease. These measures include uncontaminated water, adequate quantities of clean, well-cooked food, ventilated housing, good hygiene, efficient sewage disposal, removing or destroying sources of infection, decontamination and, if needed, quarantine for human cases and slaughter for animal infections that can affect man. These precautions were used to mitigate the effects of infectious disease before it was known that they were caused by microbes. P. Russell mentioned that one of the beneficial effects of the old epidemics was evolution of rudimentary public health measures. In developed countries, these well-established measures are now backed by good methods for recognizing and reporting outbreaks and for quickly identifying the causative micro-organisms. There are well-organized networks of regional and central laboratories, such as the British Public Health Laboratory Service and the Centre for Communicable Diseases at Atlanta, USA. These structures are remarkably strong bulwarks that can deal with untoward happenings, such as the recent outbreaks of infections from West Nile and Hantan virus.
The outstanding need is to build up the public health systems of developing nations and there are signs that the richer nations will help in this respect.
3.3. The strength of the natural defences
This topic did not receive much attention in the conference. Non-specific defences at the beginning of infection of mucous surfaces and during subsequent inflammation prevent most infections from taking hold. Immunospecific defences come into play a few days after initial infection to act specifically against the invading pathogen and in most cases lead to the patient’s recovery. These natural defences are effective against most infectious disease with the outstanding exception of AIDS. They were responsible for people recovering from disease in the past before the advent of vaccines and drugs. A. Sefton made clear that in those days only about 1/4 to 1/3 of primary cases of syphilis proceeded to the tertiary stage.
3.4. Present availability of drugs and vaccines and improvements in patient care
The pioneering work in this field by Jenner, Pasteur and Fleming was ably described by P. Beverley, M. Schwartz and C. Collins.
Many current antibiotics are broad spectrum and so are likely to be effective against newly emerging bacterial diseases. Drug resistance is a problem. However, the use of combinations of different antimicrobial drugs allows management of a significant proportion of bacterial diseases. Also, G. Duckworth described the discipline for dealing with drug resistance and both she and A.E. Allsop indicated that new drugs may be in the pipeline.
Some antiviral drugs are available and a few, like ribavirin and lamivudine, have broad spectra of activity. However, C.W. Penn had reservations about the extent of future developments, especially for therapy of less prevalent virus diseases, because, with such a small potential return, pharmaceutical companies will not bear the high cost of development.
The effectiveness of established vaccines such as those against diphtheria, whooping cough and measles was noted. D. Wood stressed the importance of two effective vaccines in the eradication programme for poliomyelitis. J. Oxford was optimistic about the production of vaccines that could cope with future drift and shift in influenza viruses, providing prior plans were made. The main problem may lie in encouraging people to take the vaccine. Potential new vaccines against malaria, plague and anthrax were described by W.H.H. Reece, D. Williamson and L. Baillie, respectively.
In addition to the impact of drugs and vaccines over the past 50 years, clinical management of cases of dangerous infectious disease, such as Lassa fever, has improved. Often patients can be kept alive for sufficient time for the immune defences to come into play and produce gradual recovery.
3.5. The impact of new knowledge
Many participants stressed that the complete genomes of some pathogens are already known and more are in the pipeline. The latest position for V. cholerae, Yersinia pestis, Francisella tularensis, B. anthracis and the malaria parasite were described by J. Heidelberg, J. Parkhill, R. Titball, T. Read and D. Carucci, respectively. M. Pallen provided good advice on how to deal with the enormous amount of data that is accumulating so that the important points emerge.
Side by side with the explosion in genomics has been the development of many new methods for detecting genes and their products expressed during infection. Two of them were described, signature tagged mutagenesis by S.N. Chatfield and proteomics by D.O’Connor. Knowledge from genomics allows the genes detected by these methods to be identified quickly. Many are involved with nutrition and metabolism. Others code for virulence determinants. Some are concerned with regulation of expression of other genes. Overall, this knowledge is being used to probe mechanisms of pathogenicity and the pattern of disease in populations, e.g. D. Young’s studies on tuberculosis. A.E. Allsop, S.N. Chatfield and many others stressed that this new knowledge would provide targets for design of new drugs, vaccines and diagnostic measures and described examples.
Infectious disease has been and still is a major problem for mankind but, despite pessimism in some quarters, mankind will cope with the situation.