Editorial Emerging, Re-emerging and Drug-resistant Infections: A Global Threat

Zent.bl. Bak te riol. 289,1-7 (1999) © Urban & Fischer Verlag

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Editorial Emerging. Re-emerging and Drug-resistant Infections: A Global Threat J.,Jeljaszewicz National Institute of Hygiene, Warsaw, Poland

Received August 24, 1998

Onl y some twenty-five years ago, the danger of plague seemed to be a historical remembrance of the past and mortality from infectious diseases as a result of a low level of hygiene and lack of effective antibiotics and vaccines. Physicians and health service administration in most industrialized coutries were convinced that infectious diseases were a vanishing problem. A promiIlent American scientist bas written in 1985 that" ... during last 150 years in the Western World, death from infectious diseases was practica lly eliminated". Such optimism seemed to be legitimated at that time. Smallpox was almost eliminated, tuberculosis and poliomyelitis morbidity were decreasing, as was the case with all major infectious threats of the 20 th century (except malaria ). Scientists were sure that due to improved sanitary conditions, vaccination and antibiotics, all infections would be quickly eliminated, and new would not a ppear. Of course, scepticism was expressed also at that time. Etiological infectious agents and insects tra nsmitting them started to show resistance to drugs and chemical agents, which until then had been so effective. Optimistic prognoses were not in keeping with what the scientists knew about the phenomenal adaptation a bilities of the microorganisms. For instance, suppositions existed that scrapie - a disease classified among the transmissible encephalopathies and occurring in sheep - has been transmitted to cattle causing bovine spongiform encephalopathy (so-called "mad cow disease") . It seems also to be probable that the etiological agent of BSE may be adaptable to humans and threaten them as Creutzfeldt-Jakob disease. We know now that prognoses of the pessimists we re right: new times have come and new infections have appeared, and microorganisms of low pathogenicity started to cause serious and life-threatening diseases. Also a number of risk factors enabling dissemination of these diseases has been increasing. At I L:nt.bL Baktcnol. 11l911

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J. Jeljaszewicz

present, scientists no longer state that medical progress will ensure elimination of all infectious diseases. It seems to be sure that when some of them will have been under control, new ones will inevitably appear. As stated by rhe Harvard Working Group on New and Resurgent Diseases in 1995, infectious diseases will always constitute a part of the human condition and scientists have to adopt this view for a better understanding of disease evolution. Instead of placing all confidence in the control of infections which have already occurred as in the past, there is a strong need for determination of factors favouring appearance and dissemination of new infections. The traditionally used term "infectious diseases" is excessively associated with the classical infectious diseases of the past caused by microorganisms. The present understanding of infectious diseases includes infections of any type. Frequently, expressions like "new diseases ", "emerging infections") "re-

surgent infections", and "drug-resistant infections " are used. The branch of science dealing with these problems is frequently called "infectiology". The World Health Report (1996), an official document of the World Health Organization, states that "Progress obtained during last decades on the way of improving human health status is now endangered. We arc at the endge of global crisis in infectious diseases. No country is safe". What does look the present situation like? Infectious diseases are the main cause of newborn death in the world and are killing at least 17 millions persons per year. The majority of these diseases, however, is within the reach of actions aimed at their elimination in few coming years. Infections with wild strains of poliomyelitis should disappear within 2-3 years. Poliomyelitis is completely absent now in 145 countries. Leprosy is slowly eliminated and within the next years will pose no serious threat for public health. Parasitic disease - dracunculiasis caused by Dracunculus medinensis, causing infection in 3.5 million people in 1986, has now been limited to 120000 in 1995. Onchocercosis, another parasitic disease casued by Onchocerca volvulus, has been eliminated in 12 countries of West Africa and Chagas disease (American trypanosomatosis ) in six countries of South America. Despite these successes, the target, j. c. the control of infectious diseases, is still very remote. Due to many reasons, infectious diseases become disseminat-

ed and their control is increasingly difficult. Emerging infectious diseases have been defined by the World Health Organization on 7 April 1997 (International Health Day ) as a m ain threat to the world. This concerns even the most developed countries. In the United States, for instance, among the commonest causes of death. AIDS, pneumonia and influenza are listed. Additionally, old habits of professional infectiologists are associated in observing major danger with mortality and not morbidity. Drug-resistant strains of bacteria and other microorganisms create a seri-

ous threat in the control of tuberculosis, malaria, cholera and other diarrhoeas, and pneumonia infections constituting a cause of death of over 10 million people in 1995. Every hour, about 50 persons die because of malaria alone.

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rable 1. Some microorganisms and infectious diseases discovered after 1972 (according to D. A. Schwartz and R. T. Bryan: Infectious disease pathology and emerging infections. Arch. Pathol. Lab. Med. 120: 11 7- 124, 1996) with some modifications) Yea r Microorganism identified

1973 1975 1976 1977 1997 1997 1997 1979 1980 1982 1982

1983 1983 1983 1983 1985 1986

1986

1986

1989 1989 1989

1990 1991

1991 1991 1992

1992

1993

Group A rotav irus

Human disease

Main cause of acute diarrhuea in the world Parvovirus B 19 Bone marrow aplasia in chronic hemolytic anem ia Cryptosporidium parlJum Acute and chronic diarrhoea Ebola feve r virus Haemorrhagic fever Ri ft Valley fever virus Febr ile disease, retinitis, fulminant hepatitis Legionella plleumophila Legionnaires' disease Hantaan virus Korean haernorrhagic fever Ross River vi rus Epidemic polya rthritis HTLV-1 (human T-cell leukemia- T-cell malignancies, tropical spastic paresis lymphoma virus) Escherichia coli 01 57:H7 Haemorrhagic co litis, haemolytic uraemic syndrome HTLV-2 Hairy cell leukemia Borrelia burgdorferi Lyme disease Hepatitis E virus «Epidemic" non-A-non-B hepatitis He/icobacter pylori Gastritis, duodenal ulcers, gastric cancer HIV-\ Acqu ired immunodeficiency syndrome (AIDS ) Enterocytozoon bieneusi Intestinal and hepatobiliary microsporid iosis HI V-2 AIDS-like illness Porogia virus Hemorrhagic fever/renal syndrome Human herpes virus 6 Roseola (exanthema suhitum ) Barmah Fores t virus Polyarthritis Chlamydia pneumoniae RespiratOry infecrioJls, ? card iovascular disease Hepatit is C vi rus Parenterall y acquired non-A-non-B hepatitis Haemophilus ill{luenzae Brazilian purpuric fever (aegypticus) Encephalitozuon hellem Di sseminated microsporidiosis Ehrlichia chafeensis Human ehrlichiosis Guana riro virus Venezuelan hemorrhagic fever l1artonella (Rochalimea) henselae Bacillary angiomatosis, cat scratch disl'ase Vibrio cholerae 0139 New strain causing epidemic cholera Septata intestinalis Intestinal and disseminated microsporidiosis

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J.Jeljaszewicz

Table 1. Continued Year

Microorganism

Human disease

1993 1993

Sin Nombre virus

Hantavirus pulmonary syndrome Leptomyxic amoebic meningoence-

1993 1994

Cyclospora cayetanensis

Coccidian diarrhoea Human granulocytic ehrlichiosis

identified Balamuthia mandrillaris Ehrlichia phagocytophila-like

phalitis

orgamsm

1994

Human herpes virus 8

Kaposi's sarcoma, body cavity

1994 1995

Sabia virus Equine rnorbillivirus

Brazilian hemorrhagic fever

lymphoma

Pneumonia

Many of the strongest antibiotics have lost their effectiveness and some bacteria are resistant to ten or more drugs. Both aetiological agents of pneumonia: Streptococcus pneumoniae and Haemophilus influenzae are becoming more and more resistant to antibiotics. Tuberculosis, thought as being under control, rapidly returns and is now a cause of 3.1 million deaths per year; drug-resistant strains of Mycobacterium tuberculosis are hecoming prevalent in several countries. Cholera, not having appeared in South America for decades, appeared in 1991 in Peru and beame rapidly disseminated throughout the continent. In the 1990's, diphteria reappeared in Russia. The largest epidemic outbreak of yellow fever since 1950 occurred in Peru in 1995. In the same year, there was an epidemic of dengue fever involving some 200000 people in Central and South America. During last twenty years, over 30 new infectious diseases have appeared. There are no drugs or vaccines to control many of them. Only fifteen years ago, HIV was not known and at present, conservative estimates calculate some 20 million cases of AIDS with a prognosis for a rise to 50 million during the next five years. In Africa, Asia, Latin America and the United States, new viruses causing hemorrhagic fevers (the best known one is Ebola virus) ha ve appeared. During an epidemic outbreak of Ebola virus infection in Zaire, over 80 per cent of patients died. A new type of Hantaan virus has appeared in the United States causing a pulmonary syndrome with a fatality rate of fifty per cent. Other hantaviruses have caused infections in Asia for many years with symptoms of hemorrhagic fever with kidney insufficiency. During recent years, several new hepatitis viruses were discovered. Some 300 million people in the world are carriers of hepatitis B virus (HBV) and an additional 100 million, of hepatitis C virus (HCV). About one quarter of these persons will die probably because of complications associated with these diseases. An increase of infections with the newly discovered hepatitis E and G viruses is also not-

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ed. A completely new strain of Vibrio cholerae 0139 appeared in India in 1992 and has spread to several other countries. Newly discovered microor· ganisms, such as Cryptosporidium parvum or new strains of bcherichia coli are causing epidemic infections transmissible through food and water both in highly and less developed countries. Viruses, bacteria and parasites appear to be closely associated with many causes of cancer. The World Health Organization estimates that about 1.5 million cases of cancer could be avoided by protection against certain infections. For intance, papilloma viruses transmissible by the sexual route seem to be responsible for the majority of 529000 cases of cervix carcinoma per year. Also every year, some 434000 cases of liver cancer (82 % of total incidence) are associated with the HBV and HCV viruses, whereas 550000 new cases of stomach cancer are associated with infections by Helicobacter pylori. In the meantime, 13 new and previously unknown species of Helicobacter have been described. Examples of new infections discovered during the last twenty years are presented in the Table. Most of them were discovered due to the progress of science, especially that in molecular biology. Some of these microorganisms appeared to be the etiological cause of commonly occurring infections, the discovery of others (HTLV, for instance) has permitted a quick discovery of HIV. These infections are not recognized and identifiable in many countries due to various reasons and their pathological effects are frequently associated with other causes; hence the treatment is not effective. This results usually from traditional views and no interest in progress of medical sciences, weak equipment and marginal role of microbiological laboratories and also, arrogance of public health service administations. The moral and material costs of not following the progress of science are difficult to estimate. Costs of well known infectious diseases are also quite high. According to U.S. estimates, the main and recognized, commonly infectious, diseases cost some 120 billion dollars pcr year in direct costs and absence from work. Of these, instestinal infections cost 32 billion, infections transmitted through food, 5-6 billion, sexually transmitted diseases (without AIDS), 5 billion, influenza - 17 billions, infections caused by drug-resistant bacteria - 4 billions (these cost arc snowballing), and hepatitis B 720 millions. At present, infections, including those listed in the Table, frequently do not express in a way typical of classical infectious disease, clinical symptoms or the simple relationship, infectious agent: disease. It appears that many external conditions may support the appearance of previously unknown infections. Such conditions are, for instance, the use of pesticides, insecticides and antimicrobial drugs, ultraviolet radiation and environmental contamination, trav-

el and migration of people, transport (of people and products), evolution and genetic changes of microorganisms, military operations, invasive medical pro-

cedures, aging of the population, infections lowering innate immunity (HIV), social and political instability, wars and mass migration of poeple, poverty and malnutrition, increase of the population and its density, climate changes,

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J. Jeljaszewicz

urbanization, agriculture development, forestation of new territories or deforestation.

Some examples will be cited which follow the above reasoning. The appearance of Argentinian and Bolivian hemorrhagic fever is associated with changes in agriculture favouring a multiplication of rodents; bovine spongiform encephalopathy, with a consumption of mea ls contaminated with prions; dengue with increases of transport, travel, migration and urbanization, hemorrhagic fever in Europe and the United States with the importation of infected monkeys; HCY, HGY, HIY with transfusions of blood and its fractions (for instance in hemophiliacs), organ transplantation, sexual contacts; yellow fever in "new areas" with favorable conditions for mosquito multiplication, Similar examples are available for bacterial infections, for intance, Escherichia coli 0157: H 7 infections are associated with a contamination of food in mass production of meat, Legionnaires disease with the presence of Legionel/a pneumophila in hyd raulic cooling systems and neglected water containers, Lyme borreliosis with forestation around homes and favorable conditions for the multiplication of ticks. Infections by cryptosporidia are due to infected surface water or improper water purification, and the appearance of malaria in new regions, with travel and migration. Chronic infections may appear as a cause of diseases which were never associated before with an infection. Intracellular infection with cytomegalovirus may lead to congenital mental defects; HBY is frequently a cause of chronic hepatitis, cirrhosis and liver cancer, similarly as HCY; chronic infection with some papilloma viruses is associated with cervical and larynx cancer. Borrelia burgdorferi may cause arthritis, Chlamydia trachomatis, infertility, Escherichia coli 0157: H7, hemolytic ureamic syndrome, Helicobacter pylori, peptic ulcer, Toxoplasma gondii, inborn mental defects. In some cases, this causesresult relationship is very well documented, whereas in others, further investigation and observations are necessary. Hypotheses exist, although rather weakly documented at this time, suggesting following results of infections: enteroviruses (especially Coxsackie) - type 1 diabetes, hantaviruses - arterial hypertension, HCY -liver cancer, HPY - lung and bladder carcinoma, Campylobacter jejuni - Guillain-Barre syndrome, Chlamydia pneumoniae - arterioscelorosis, superantigens of Staphylococcus au reus - Kawasaki disease. A separate pro blem is posed by infections caused by bacteria resistant to the action of antimicrobial agents. In a certain sense, these are also "new infections ", as resistant strains differ from maternal populations. During the last twenty years, large pharmaceutical companies have neglected the search for new antimicrobials and antibiotics which have appeared during that time were indeed only versions of the existing drugs. There is even the question whether the era of classical antibiotics is slowly passing away and the control of new infections requires perhaps agreat breakthrough such as the discoveries of penicillin or semisynthetic antibiotics. It is, a fact thar populations of bacteria resistant to most of antibiotics very rapidly increase. More and more frequently rhese bacteria are components of normal human fiora, previously

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not causing infections (as, for instance, enterococci now being resistant to practically all antimicrobials). There is an urgent need for molecular epidemiology to analyze the antibiotic-resistant strains. Their main source are hospitals, where two factors are supporting each other: circulation of strains with multiple antibiotic-resistance patterns and possibly increased virulence and inevitability of hospital infections. A complete eradication of hospital infections seems to be very difficult if at all achievable, but lowering their incidence is possible by appropriate measures. Infectious diseases at the turn of the century are different from those in the past but constitute a global threat in any country of the· world. Improvement and broadening of both the technical diagnosis of these infections and also of the minds of infectious disease professionals seems to be a necessity. Corresponding author: Prof. Dr. Janusz Jeljaszewicz, N ational Institute of Hygiene, 24 Choeimska, PI.-OO-791 Wa rsaw, Poland, Tel.: +4822-497612, Fax: +4822-497484