No 1/2 - 2013

Infectious diseases 2012

Antimicrobial drug resistance

The fight against antimicrobial resistance was a focus area during the Danish EU Presidency in the first half of 2012. In this context, the European conference "Combating Antimicrobial Resistance – Time for Joint Action" took place on 14-15 March 2012 in Copenhagen. The conference was organised by the Danish Ministry of Health and the Danish Ministry of Food, Agriculture and Fisheries.

The conference targeted the increasing global threat from antimicrobial drug resistance and the use of antimicrobials in animals as well as humans. The objective of the conference was to exchange best practices, raise awareness of the microbial threat and motivate member states and stakeholders to instigate joint action.

That the current situation is serious and worrying was made clear by the WHO's Director General, Margaret Chan in her opening speech. She stressed that, if we fail to act, we will be entering a post-antibiotic era in which antibiotics will no-longer be effective.

"A post-antibiotic era means, in effect, an end to modern medicine as we know it. Things as common as strep throat or a child’s scratched knee could once again kill. Some sophisticated interventions, like hip replacements, organ transplants, cancer chemotherapy, and care of preterm infants, would become far more difficult or even too dangerous to undertake."

With these words Chan made it clear that effective antibiotics are pivotal to modern healthcare. That the threat is far from idle was underlined in 2012 by the detection of several cases of enterobacteria resistant to carbapenems (CPE), EPI-NEWS 10/12 and 42-43/12. Carbapenems are the last effective treatment option for e.g. serious infections caused by particularly E. coli and Klebsiella pneumoniae resistant to third and fourth generation cephalosporines.
Not only are the CPE infections extremely difficult to treat with antibiotics; the bacteria carry the potential to establish and spread at hospitals and in the community. This is equivalent to trends seen previously for multi-resistant ESBL (extended spectrum beta-lactamase) producing enterobacteria, as some of these types have caused nosocomial infections, EPI-NEWS 39b/12.

After the conference held in March, the EU Presidency presented Council conclusions focussing on prudent use of antimicrobials. The conclusions encourage EU member states to develop and implement national strategies or action plans to counter resistance. The conclusions were adopted by EU ministers at an EPSCO meeting on 22 June 2012.

It will be interesting to see if the needed political courage and will is present to follow up on these conclusions through implementation in national legislation and modification of national guidelines on monitoring of infections and antibiotic treatment of humans and animals. It will prove hard to follow-up on conclusions unless resources are allocated to strengthen national as well as international infection preparedness, disease monitoring and research efforts.

Among the national measures of 2012, the annual Antibiotic Awareness Day and the associated information campaign on rational use of antibiotics targeting the general population deserves mention (www.antibiotikaellerej.dk). The Danish Health and Medicines Authority published a guideline for use of antibiotics, primarily to limit ineffective and unnecessary antibiotic treatment and target and limit the use of the critically important antimicrobials: carbapenems, fluoroquinolones and cephalosporines, EPI-NEWS 51a/12. In 2012 the Danish Medical Association, the Danish Veterinary Association and the Danish Regions actively contributed to follow up on the issues relevant to antimicrobial resistance.

Climate change and infectious diseases

Past years have witnessed discussion of the consequences of global heating on human health, including the occurrence of infectious diseases. There is consensus that the consequences for developing countries may be considerable as drought, flooding and extreme weather may affect food production, increase poverty and inequality, and also change the prevalence of e.g. vector-borne and water-related diseases.

The scope of the consequences for the Western industrialised world is less certain. Our part of the world has more resources available to adapt to climate change. Some climate changes may even have beneficial effects, as a milder climate in the Nordic countries would allow populations to spend more time outdoors in the colder parts of the year which would, in turn, limit the number of airway infections among children attending day-care institutions.

However, over the past few years, we have seen examples that Europa will also suffer negative health consequences from climate change. In 2012, a very large outbreak of dengue fever in Madeira including more than 2000 verified cases deserves mention. Some of the cases were detected in tourists, including two Danes. Additionally, Greece – for the second year running – witnessed local transmission of malaria. Moreover, the prevalence of other vector-borne diseases also follow an increasing trend, including chikungunya fever, tick-borne encephalitis, West Nile virus, EPI-NEWS 6/12, and Crimean-Congo haemorrhagic fever. Caution is necessary when interpreting these trends as climate change is but one among several contributing factors.

Another example of consequences of climate change is health problems caused by extreme weather (torrential rain storm). In the aftermath of a major rain storm in Denmark in July 2011, five persons were notified with leptospirosis. Two were admitted to hospital and one died, EPI-NEWS 34b/11 and 5/12. Furthermore, a questionnaire including 257 persons with occupational exposure to rainstorm water showed that 22 % had fallen ill. The questionnaire also demonstrated that disease was associated with smoking (hand-mouth contact) and lack of hand washing.

Diarrhoeagenic E. coli

Denmark has so far not been exposed to general food-borne outbreaks caused by the "burger bug" E. coli O157, the particularly aggressive variant associated with a high risk of complications in the form of haemolytic uraemic syndrome (HUS). The outbreak in September-October 2012, EPI-NEWS 45/12, was the first Danish food-borne outbreak of such a HUS-associated type, and it brought a very high number of HUS cases relative to the number of patients presenting with diarrhoea only.
The outbreak was relatively limited in scope as the source of infection was presumably ground beef which has a limited shelf life and is primarily used in dishes which require thorough cooking. If the source of infection had been a food product with a longer shelf life, or had been continuous in nature, the scope and consequences of the outbreak would probably have been more severe.

The outbreak demonstrates the importance of notifying HUS cases without undue delay. In line herewith, rapid and timely diagnostics of verocytotoxin-producing E. coli (VTEC) is essential to the management of the affected patients as well as infection tracing. The outbreak gave rise to debate on the indications for testing of faeces for VTEC and other types of diarrhoeagenic E. coli.

The delimitation of "gastrointestinal pathogenic bacteria" to salmonella, shigellosis, Yersinia enterocolitica and campylobacter is an outdated convention which is not evidence-based. Overall, the diarrhoeagenic E. coli cause diarrhoea more frequently than the mentioned bacteria; apart from Campylobacter jejuni which is the most common cause of bacterial gastroenteritis in Denmark. Choosing not to investigate for diarrhoeagenic E. coli when diagnosing significantly reduces the benefit of faeces culture. If clinical or epidemiological indication supports testing for gastrointestinal pathogenic bacteria, it will mostly be relevant to test for diarrhoeagenic E. coli. On this basis, the Danish Society for Clinical Microbiology recommends that all children below 7 years of age with diarrhoea – and any patient with bloody diarrhoea, regardless of age – are tested for diarrhoeagenic E. coli by molecular biology diagnostics.

New corona virus

September brought the detection of a new corona virus in two persons from Saudi Arabia and Qatar, respectively. These patients had suffered from severe airway infections, and the health authorities and public health institutions reacted promptly to the findings by establishing measures to diagnose and monitor the new virus. Diagnostic capacity was also established rapidly in Denmark, and a well-functioning joint national response tested several persons, who all tested negative to the new virus. The reason that the new virus sparked the establishment of national preparedness measures is that it was another corona virus that caused the 2003 SARS outbreak.

SARS was a severe acute respiratory infection, and the SARS outbreak placed the healthcare systems of several countries under considerable pressure and indirectly had a pronounced negative socio-economic impact, particularly in Asia and Canada. On that basis, the international reaction on the identification of the new corona virus was justified.

Luckily, the finding of a new corona virus did not mark the beginning of a new SARS outbreak. The new virus was not very infectious, and a total of nine persons were notified with infection caused by the new corona virus in 2012. The cases were from Jordan, Saudi Arabia and Qatar, and all suffered severe infections; five persons died. It is therefore relevant to be aware of this new virus as a differential diagnostic option in severe infections among patients who have stayed on the Arabian Peninsula or in the Middle East.

Whooping cough

Preliminary figures for 2012 show that the SSI laboratory detected more than 500 cases of whooping cough (all ages) compared with a total of 140 cases in 2011. The overall number of laboratory diagnosed cases in 2012 will exceed 1,000 as more and more local DCMs detect whooping cough. As previously stated, EPI-NEWS 41/12, the majority of the observed increase may be explained by an increased use of serology as a diagnostic method in older children and adults with cough lasting more than two weeks.

A similar increase was seen in other countries following the introduction of this diagnostic method. This demonstrates that the disease is under-diagnosed. 2012 saw a total of 146 notified cases of whooping cough among children below the age of 2 years, as compared with 70 in 2011. Consequently, considerably more cases were detected in 2012 than in 2011, when the incidence was low. It is possible that part of the increase reported among young children may be ascribed to increased awareness about the diagnosis and increased diagnostics (primarily PCR diagnostics), but a considerable share of the observed increase is probably real.

Whooping cough is a very infectious disease, and a considerable share of the population is susceptible to infection. Neither full vaccination nor natural whooping cough infection yields permanent protection. Whooping cough epidemics typically occur in a cyclic pattern, and it is probable that epidemics will occur regardless of the vaccination programme. Consequently, the main objective of the vaccination programme is to prevent serious infections in neonates and infants. In an effort to optimize this programme, some countries have chosen to introduce a booster vaccination for teenagers (to limit infection within families and in institutions, and possibly protect young mothers, when these teenagers grow up), while England introduced a vaccine for pregnant women (to indirectly protect neonates) in 2012.

An overall assessment of the Danish situation would require an analysis of the patterns of diagnostics and disease incidence, including the 2013 trend. It would also be relevant to assess the Danish Childhood Vaccination Programme, including among others, the effect of the existing five-year booster. Finally, the analysis should include experiences reported from other countries.

The whooping cough situation and the vision of eliminating measles show that it is important that healthcare professionals as well as the population in general support the Danish Childhood Vaccination Programme. On this note the Department of Infectious Disease Epidemiology wishes all readers of EPI-NEWS a happy new year.

(K. Mølbak, Department of Infectious Disease Epidemiology)

Link to previous issues of EPI-NEWS

9 January 2013