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New diseases and renewed threats

During the past 20 years, at least 30 new diseases have emerged, for many of which there is no treatment, cure or vaccine, or the possibility of effective prevention or control. In addition, the uncontrolled and inappropriate use of antibiotics has resulted in increased antimicrobial resistance and is seriously threatening drug control strategies against such common diseases as tuberculosis, malaria, cholera, dysentery and pneumonia.


EMERGING infectious diseases are those whose incidence in humans has increased during the last two decades or which threatens to increase in the near future. The term also refers to newly-appearing infectious diseases, or diseases that are spreading to new geographical areas - such as cholera in South America and yellow fever in Kenya. It refers also to diseases that were easily controlled by chemotherapy and antibiotics, but which have developed anti-microbial resistance.

The diseases in question involve all the major modes of transmission - they are spread either from person to person, by insects or animals, or through contaminated water or food.

The most dramatic example of a new disease is AIDS, caused by the human immunodeficiency virus (HIV). The existence of the virus was unknown until 15 years ago, but it has since then infected an estimated 24 million adults worldwide, and that number could grow to a cumulative total of 40 million by the year 2000.

The origins of HIV are unknown, but it is related to viruses which cause AIDS-like illness in monkeys. Microorganisms constantly undergo changes that enable them to cope with an increasingly hostile environment in their hosts. For example, HIV exploits weaknesses in the host's defences by damaging the human immune system, thereby allowing other 'opportunistic' infections to take advantage.

A new breed of deadly haemorrhagic fevers, of which Ebola is the most notorious, has struck in Africa, Asia, the United States and Latin America. Ebola appeared for the first time in Zaire and Sudan in 1976; it has since struck in Cote d'Ivoire in 1994 and 1995, Liberia in 1995 and again in Zaire in 1995, where it was fatal in 77% of cases. The natural carrier of the Ebola virus - presumably an animal - has not been identified.

20 states

The United States has seen the emergence of hantavirus pulmonary syndrome, characterised by respiratory failure and a case fatality rate of over 50%. Since it was first recognised in 1993, this type of hantavirus infection has been detected in more than 20 states in that country, and has also surfaced in Argentina and Brazil. This hantavirus is carried by rodents, particularly deer mice, and other hantaviruses have been recognised for many years in Asia, where they cause haemorrhagic fever with renal involvement in humans.

Epidemics of food-borne and water-borne diseases due to new organisms such as cryptosporidium or new strains of bacteria such as Escherichia coli have hit industrialised and developing countries alike. The O157:H7 strain of E.coli was first reported in 1982 and has since then been implicated in many serious outbreaks of diarrhoeal illness, sometimes leading to kidney failure. The strain has been linked to undercooked hamburger beef and unpasteurised milk.

A completely new strain of cholera, 0139, appeared in south-eastern India in 1992 and has since spread north and west to other areas of India, into western China, Thailand and other parts of South-East Asia.

The threat of a new global influenza pandemic is increasing. Major shifts in the make-up of influenza viruses occur every 20 years or so, triggering large epidemics in many parts of the world, and causing many thousands of deaths. The next such shift is expected to take place very soon.

Epidemic strains of influenza viruses originate from China. The influenza virus is carried by ducks, chickens and pigs raised in close proximity to one another on farms. The exchange of genetic material between these viruses produces new strains, leading to epidemics of human influenza, each epidemic being due to a different strain.

New strains such as those of cholera and influenza do not follow the usual pattern of being more common in younger people. They affect all age groups, since older people have not acquired immunity to them from previous infection.

The emergence of drug-resistant strains of microorganisms or parasites is promoted by treatments that do not result in cure. The increasing use of antimicrobials worldwide, often in subtherapeutic doses and sometimes in counterfeit form, guarantees that this problem will increase in the foreseeable future....

Changes in lifestyle, behaviour (including injecting and non-injecting drug use) and cultural or social values are behind the emergence of some infectious diseases such as syphilis. Increases in the number of sexual partners have been the main factor in the spread of HIV infection and other sexually transmitted diseases.

Travel, including tourism, also plays a role. The spread of syphilis in the 18th and 19th centuries was related to the movement of armies. Today, the introduction of HIV in many parts of the world is due to greatly increased human mobility. Studies show that whereas only a few generations ago most people in their lifetime travelled no further than 40 kilometres from their birthplace, many today go up to 1,000 times further, travelling the whole world.

The practices of modern medicine also contribute. The spread of viral hepatitis is related in part to techniques such as kidney dialysis and multiple blood transfusions, as well as to other forms of transmission.

Relaxation in immunisation practices can quickly result in the resurgence of diseases, as, for example, the recent spread of diphtheria in the Russian Federation and other former republics of the USSR.

New animal diseases pose potential food-borne risks to human health that are sometimes difficult to evaluate or predict. An example that has caused much public concern in Europe is bovine spongiform encephalopathy ('mad cow disease'). Fears have grown that the infectious agent responsible may be passed through the food chain to cause a variant of the incurable Creutzfeldt-Jakob disease in humans, in which the brain is attacked. The British beef market has been seriously affected and stringent public health safeguards have been introduced.

The reasons for outbreaks of new diseases, or sharp increases in those once believed to be under control, are complex and still not fully understood. The fact is however that national health has become an international challenge. An outbreak anywhere must now be seen as a threat to virtually all countries, especially those that serve as major hubs of international travel.

Despite the emergence of new diseases in the last 20 years, there is still a lack of national and international political will and resources to develop and support the systems that are necessary to detect them and stop their spread. Without doubt diseases as yet unknown, but with the potential to be the AIDS of tomorrow, lurk in the shadows.

Antimicrobial resistance

Resistance by disease-causing organisms to antimicrobial drugs and other agents is a major public health problem worldwide. It is making a growing number of infections virtually untreatable, both in hospitals (as discussed in the later section on hospital infections) and in the general community. It is having a deadly impact on the control of diseases such as tuberculosis, malaria, cholera, dysentery and pneumonia.

Antimicrobial resistance is not a new problem, but it has worsened dramatically in the last decade. During that time, the pace of development of new antimicrobials has slowed down while the prevalence of resistance has grown at an alarming rate. The increase in the number of drug-resistant bacteria is no longer matched by a parallel expansion in the arsenal of agents used to treat infections.

In this situation, doctors and their patients are more and more helpless. All age groups are affected. The elderly, the very young, the chronically ill and people whose natural defences are weakened by disease or medical treatment such as surgery are at greater risk of drug-resistant infections, but healthy people in the prime of life can also be attacked. Resistance to antibiotics and other drugs means that people with infections are ill for longer periods, and are at greater risk of dying, and that disease epidemics are prolonged.

All bacteria possess an inherent flexibility that enables them, sooner or later, to evolve genes that render them resistant to any antimicrobial. By killing susceptible bacteria, an antimicrobial provides selective pressures that favour overgrowth of bacteria carrying a gene that confers resistance. The continuous use of antimicrobial agents encourages the multiplication and spread of resistant strains.

There is strong evidence that a major cause of the current crisis in antimicrobial resistance is the uncontrolled and inappropriate use of antibiotic drugs, in both industrialised and developing countries. They are used by too many people to treat the wrong kind of infection, in the wrong dosage and for the wrong period of time.

The implications are awesome: drugs that cost tens of millions of dollars to produce, and take perhaps 10 years to reach the market, have only a limited life span in which they are effective. As resistance spreads, that life span shrinks; as fewer new drugs appear, the gulf widens between infection and control. So far, the pattern of excessive or inappropriate use and the development of resistance has been repeated after the introduction of each new antimicrobial.

The overuse of expensive drugs designed to cover a range of infections is a particularly serious problem in industrialised countries. In developing countries, the problem is compounded by the ready availability of over-the-counter drugs. This allows patients to treat themselves, either with the wrong medicine, or in quantities that are too small to be effective. Substandard and counterfeit drugs which lack adequate amounts of active ingredients further exacerbate the resistance problem.

Resistance has no natural barriers; its development in the most remote locations can lead rapidly to a worldwide impact, aided by international air travel.

Furthermore, enormous amounts of medical antimicrobials are used for the production of animal food around the world. Some 170 billion tons of animal meat are produced worldwide every year. More than half the total production of all antimicrobials is used in farm animals, either for disease prevention or for growth promotion. Drug-resistant bacteria are passed through the food chain to the consumer, where they may cause disease or transfer the resistance to human pathogens.

Examples of bacterial resistance

Enterococci contribute to some of the most common infections acquired in hospitals, causing intra-abdominal abscesses, endocarditis, and infections of the urinary tract and soft tissues. In some countries, infections resulting from strains resistant to the main groups of antibiotics, such as the beta-lactams and the aminoglycosides, can only be treated with vancomycin, an expensive intravenous drug. Even resistance to vancomycin has developed in the last 10 years or so. In the United States in 1994, 14% of enterococci isolated from patients in intensive care units were resistant to vancomycin.

Staphylococci, which can contribute to skin infections, endocarditis, osteomyelitis, food poisoning and other serious disorders, have developed resistance to all antibiotics except vancomycin. If vancomycin-resistant strains were to emerge, some of the most prevalent hospital-acquired infections would become virtually untreatable .

Streptococci have become increasingly resistant to some antibiotics in the last 25 years. They are among the most common disease-causing bacteria, responsible for infections of the throat, middle ear, skin and wounds, and also necrotising fasciitis and gangrene.

Pneumococci and Haemophilus influenzae are the most common bacteria causing acute respiratory infections in children, particularly pneumonia. Both of these organisms are becoming more and more resistant to drugs. Strains of pneumococci, once uniformly susceptible to penicillin, are currently resistant to it in up to 18% of cases in the United States and 40% in South Africa. In addition, they are becoming resistant to many other commonly used antibiotics, including cotrimoxazole, the drug recommended by WHO for treatment of pneumonia. The most virulent type of Haemophilus influenzae is today frequently reistant to ampicillin, and strains have been identified that are resistant to other drugs, including cotrimoxazole. In brief, doctors worldwide are losing some of the most useful and affordable antibiotics agains the two bacteria which are the major cause of death in children.

Neisseria gonorrhoeae, cause of one of the most common sexually transmitted diseases, has acquired such resistance to penicillin and tetracyclines in most countries that the use of these antibiotics to treat it has become unacceptable and this infection now requires the use of much more expensive drugs which are often unavailable.

Shigella dysenteriae has been causing outbreaks of severe diarrhoeal disease in central and southern Africa in recent years, including those in refugee camps, with the epidemic strain acquiring increasing resistance to standard antibiotics. Epidemic dysentery caused by this strain results in the death of up to 15% of those infected.

Salmonella typhi, the bacterium responsible for typhoid fever, has developed resistance to anitbiotics commonly used in the past for treatment. Resistant strains have caused outbreaks of the disease in India and Pakistan in recent years. Without effective antibiotic treatment, typhoid fever kills almost 10% of those infected. In South-East Asia, 50% or more of the strains of the bacteria may already be resistant to several antibiotics.

More than half of the antibiotics produced worldwide are used in animals, largely in subtherapeutic concentrations which favour the onset of drug resistance. As a result, two important human pathogens of animal origin, E.coli and salmonellae, are today highly resistant to antibiotics in both industrialised and developing countries. For instance, in the United Kingdom, the increase of multidrug-resistant strains of Salmonella typhimurium isolated from cattle is paralleled by increasing resistance among strains of human origin. In Thailand, salmonellae isolated from food animals are also highly resistant to the common antibiotics. These bacteria cause diarrhoeal disease and can lead to life-threatening complications. Due to the globalisation of food supply and international travel, anitmicrobial resistance among animal bacteria can affect consumers anywhere in the world.

Strains of M.tuberculosis resistant to antituberculosis drugs are widespread, although attention has recently focused on the alarming outbreaks of tuberculosis caused by multidrug-resistant strains in the United States. Drug resistance is the result of poor prescribing practices, or poor patient compliance with treatment. It is low in the few countries with effective tuberculosis programmes. The most dangerous form of the multidrug-resistant disease occurs when cases become virtually incurable and doctors face situations similar to those of the pre-antibiotic era.

Malaria presents a double resistance problem: resistance of the Plasmodium parasites, which cause the disease, to antimalarial drugs; and resistance of the Anopheles mosquitos, the vectors of the disease, to insecticides. The arsenal of antimalarial drugs is limited. Most of them act by killing parasites when they are multiplying in the blood stream of the human host. Unfortunately, due to inadequate regimens, poor drug supply and poor quality and misuse of drugs, rapid development of drug resistance has occurred in most areas of the world. Drug resistance is particularly important in falciparum malaria, the most severe form of the disease. Resistance to chloroquine, the most commonly used drug, has been found in all endemic countries except those of Central America and the Caribbean. Resistance to multiple drugs is common in South-East Asia.

This serious obstacle to malaria control efforts is further complicated by mosquito resistance to insecticides. Many mosquitos are reported to be resistant to the three classes of insecticides available for public health use, and some are becoming resistant to pyrethroids, widely promoted for bednet and curtain impregnation.

Outlook

The next few years are certain to be critical for the future of antimicrobial drugs. Antimicrobial resistance will increase if present trends continue. Doctors in many parts of the world could find themselves resorting to methods that date back to before the antibiotic era. For instance, in New York City, patients with multidrug-resistant tuberculosis who will not voluntarily comply with recommended treatment are sometimes isolated on a former prison island, used much as sanatoria were used in the past.

Disease control strategies will be seriously threatened by mounting drug resistance levels among bacteria which cause the most important and frequent diseases worldwide. Developing countries, where the burden of infectious diseases is the highest, will be facing the impossible task of controlling diseases with only scarce expensive drugs which will not be affordable for all sick persons. - WHO Report 1996

 

 

 

 


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