Antibiotic-resistance, Avian Flu And Other Viral Epidemics At ECCMID In Nice

16th European Congress of Clinical Microbiology and Infectious Diseases

Nice, France – Globalisation is a phenomenon involving ever wider spheres: economic, social, cultural, and religious. But these are not the only areas to be affected. Fading national boundaries caused by intensification of commercial trading and increased migration, as well as the tendency for more “exotic” tourism, has caused a globalisation of infectious diseases that is involving all European countries.

This is the background to the importance of a European organisation such as ESCMID (European Society of Clinical Microbiology and Infectious Diseases), which pursues as its major goal the improvement of the diagnosis, prevention and clinical management of infections, including those with a high public health impact.

Indeed, there is currently a paradoxical situation: despite the enormous progress made in medical science, there are new diseases emerging, either as adaptations of existing diseases which lose their responsiveness to traditional treatments, or as new diseases based on previously unknown pathogens for which a mode of transmission and control still have to be established and treatment regiments still to be developed.

The ECCMID (European Congress of Clinical Microbiology and Infectious Diseases), organized by ESCMID in Nice from 1 – 4 April 2006, is the most important annual event of its kind in Europe. Now in its 16th edition, the Congress unites a large number of European and other international experts and over 6000 delegates with the aim of increasing knowledge and discussing future research, treatment and public health strategies needed to tackle infectious diseases.

Resistance to antibiotics

The first problem, the loss of efficacy in treating some common infectious diseases, is predominantly due to antibiotic resistance. The alarm raised by infection experts is serious: the dramatic increase of bacteria resistant to antibiotics paralleled by a lack of new antibiotics has already led to infections being no longer curable.

In fact, it has been seen that some pathogens, particularly those occurring in hospitals (e.g. Staphylococcus aureus and Pseudomonas aeruginosa), are now extensively resistant to widely used antibiotics. Furthermore, recent studies have demonstrated that genes conveying antibiotic resistance can spread between different strains even across species barriers. Combined, all of the above leads to an ever increasing number of difficult-to-treat bacterial infections. In the case of Pseudomonas, but now even in the case of common and “easy-to-treat” bacteria such as Escherichia coli, the most recent and dangerous mechanisms of resistance are the so-called “carbapenemase” enzymes, which attack and destroy the most frequently used antibiotics and make bacteria, which produce these enzymes, resistant to all drugs.

The problem of antibiotic-resistance is further worsened by the disinvestment of several pharmaceutical companies in the field of antibiotic research and development and the resulting shortage of new drugs.

The experts at ECCMID therefore consider measures to contain antibiotic resistance by optimally using the currently available drugs absolutely essential.

“The key to controlling the development of antibiotic resistance”, explains Prof. Hermann Goossens of the Department of Medical Microbiology at Antwerp University Hospital, Edegem, Belgium, “is the ability to choose antibiotics selectively.” Making a precise diagnosis and understanding the probable aetiology should enable the correct treatment of the main community-acquired infections. “However, in order to do this,” continues Goossens, “it is very important that fast, new diagnostic tools are developed for the identification of diseases of bacterial origin. This would permit the prescription of antibiotics only in the case of real need.”

Although the main cause of antibiotic resistance in community-acquired infections is inappropriate prescribing of antibiotics, another important factor is patients’ non-compliance.

It has, in fact, been demonstrated that the therapeutic efficacy of antibiotics also depends heavily on patients respecting the prescriptions and instructions received from their doctors about the correct dose, the dosing interval and the duration of treatment.

Prevention is another aspect that should not be forgotten when discussing antibiotic resistance. It was found that the introduction of the pneumococcal conjugate vaccine in Europe often coincided with a decrease in the resistance to macrolides and to penicillin. Streptococcus pneumoniae, also called pneumococcus, is one of the most important pathogens of the respiratory tract, with a high frequency of resistance to commonly used antibiotics.

Another important factor for treating infectious diseases and surveillance of resistance is the definition of “susceptible” or “resistant” pathogens; paradoxically, these definitions are not the same in all European countries.

In this regard, ESCMID has convened a strategically important committee, called EUCAST (European Committee on Antimicrobial Susceptibility Testing), with the goal to produce uniform guidelines for susceptibility testing of antibacterial drugs and to define “breakpoints” (that is, the values differentiating susceptible form resistant bacteria) in Europe.

The importance of tackling resistance through co-ordinated action of all European countries is further confirmed by the support that ESCMID gave to the creation of GRACE (Genomics to combat Resistance against Antibiotics in Community-acquired LRTI in Europe), a network of excellence financed by the European Union which brings together major European experts to increase knowledge, guarantee the practical application of research, develop new diagnostic tests and improve the prescribing habits and training of health care workers.

Avian flu

Another issue discussed in particular detail by the experts at ECCMID was avian flu. “Also in this case,” said Albert Osterhaus, Head of the Department of Virology and Director of the National Influenza Centre, Erasmus Medical Centre, Rotterdam, “a better co-ordination is needed in Europe among all the stakeholders, researchers, public health care workers and veterinarians in order to prevent a possible pandemic. This can be achieved by creating a European task force to share knowledge and to tackle the possible risks.”

Osterhaus continued, “So far, the crisis in Europe has predominantly affected the avicultural sector. Community regulations to safeguard this production chain and those working in the sector are needed. The most important message to convey to the population is that of not confusing the problems related to the avicultural sector with the possibility of a pandemic developing.”

Scientific societies, such as ESCMID, which have access to a network of experts throughout the continent, can contribute to this co-operation by acting as interlocutor with academia, health authorities of individual states, the European Commission and the EDCD (European Centre for Disease Prevention and Control).

Ragnar Norrby, Director of the Swedish Institute for Infectious Diseases Control in Stockholm and current President of the ESCMID, re-addressed the “basic” information to be conveyed to the population, confirming that “avian flu is a disease of birds and that the risk of humans catching the infection, although theoretically possible, is very low and limited to those people who have direct contact with infected birds. However, as of today, there is no convincing evidence of man-to-man transmission.”

Turkey, the only large reservoir so far observed in Europe, is a paradigmatic example: the cases of transmission of the virus to humans was limited mainly to the rural areas, where direct contact with animals is frequent, and did particularly involve children who have deliberately touched dead or sick birds. Also in these cases, the danger can be limited by applying ordinary rules of hygiene such as frequent hand-washing, not eating meat that is of suspicious provenance or poorly cooked and prohibiting hunting within a 10 km radius of where an animal infected by H5N1 has been found.

Although the H5N1 virus (responsible for avian flu) can cross the barriers between species and infect other animals, such as cats, so far the virus has not spread from cats to different species.

Concerning the possibility of a pandemic to occur, Norrby emphasized that “the worldwide spread of influenza among humans occurs when a new influenza virus develops, usually as a result of recombination of genetic material from a human influenza virus with genetic material from an animal influenza virus. A pandemic virus can, therefore, arise anywhere in the world, but the probability is higher in countries with a high population density and many domestic birds and pigs such as in Asia or Africa.”

“So far,” continued Norrby, “pandemics have developed at irregular intervals (Spanish ‘flu in 1918, the Asiatic pandemic of 1957 and the one arising in Hong Kong in 1968). Therefore, although it can be presumed that another will occur, no-one is able to predict when and with what variant of the influenza virus”.

Norrby concluded, “it is important to emphasize two aspects: although the high density of H5N1 virus in birds from all over the world (and particularly in Asian and African countries) facilitates the development of a pandemic infection caused by the virus, the fact that millions of Asians have probably been in contact with infected, dead birds since 1997 (the year in which the first severe spread of avian flu occurred in Hong Kong) without the virus having mutated into a pandemic variant, speaks against a variant of H5N1 virus becoming a pandemic virus.”

As far as regards the availability of a human vaccine against avian flu, it was repeated during the ECCMID Congress that large-scale production of such a vaccine requires from four to six months. Considering that avian influenza has had a seasonal trend so far, affecting the population during the winter in countries with a temperate climate, it is probable that if a vaccine is needed it will be scarce during the first wave of infections, but fully available for the second season.

The most important antiviral drug on the market is oseltamivir (Tamiflu), since it has few side effects and is easy to administer. It is important to highlight that oseltamivir can be used for prophylaxis, but considering that the influenza season lasts four to six months it is not feasible to store the supplies necessary to administer the drug to a large number of people. Although studies have not been carried out in patients infected by H5N1, it has been documented that in order to reduce the duration and the severity of symptoms, oseltamivir-based treatment must be administered within 48 hours of the onset of the symptoms. It is also important to remember that treatment with antiviral agents can lead to the development of resistance.

Finally, it should be appreciated that – even in the absence of a vaccine against avian influenza – primary prevention, in particular vaccination against “common” influenza and pneumococcal respiratory infections, plays an essential role in the defence against a possible pandemic.

In fact, immunization could increase resistance to strains never previously encountered, such as a potentially pandemic virus. For example, in the case of the H5N1 strain, it is known that N1 (neuroaminidase 1) is contained in other viruses and vaccines. It is, therefore, possible that a previous infection or vaccination with virus containing N1 can provoke a certain response that then remains in the immunological “memory” of the individual.

Antipneumococcal vaccination should also play a strategic role in prevention, since it has been demonstrated that a considerable proportion of the pulmonary complications in previous pandemics was linked to superimposed bacterial infections, including those caused by pneumococci.

Chikungunya

During the ECCMID another epidemic was discussed: chikungunya, a rare viral disease transmitted by mosquitoes (Aedes albopictus). This epidemic appeared one year ago in La Rйunion, where 186,000 cases, including 93 deaths, have been registered so far. The infection has spread to Mayotte (924 cases), to the Seychelles (4650 suspected cases), to Mauritius (2553 cases notified, of which 1173 confirmed) and to Madagascar (sporadic cases). In Europe “imported” cases have been reported in France (n=160), Switzerland (n=12) and Germany (n=4).

The current level of risk of chikungunya (a fever that causes violent joint pains) being introduced into Europe is low, given the unfavourable climatic conditions in this period of the year, although the risk cannot be excluded completely. There is lack of consensus on whether there will be a real risk of autoctonous spread of the virus in the warmer season, when the number of mosquitoes increases.

What is certain, as concluded by the experts meeting at the ECCMID, is the need to activate close monitoring of the epidemic at a European level and to identify efficient diagnostic tools.

escmid

View drug information on Tamiflu capsule.

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