N E W S L E T T E R O F F E M S F E D E R AT I O N O F E U RO P E A N M I C RO B I O L O G I C A L S O C I E T I E S

Spring is here. After the cold and dark winter days here in Europe, and in some occasions even devastating, everybody is excited to experience longer and warmer days. This means the sun is coming out, flowers are blooming and animals are giv-ing birth. This also means a sudden burst of microbes in the air called Coxiella bur-netii. Difficult to pronounce and harder to spell, this bacterium causes the Q fever outbreak every year in many countries, but in the Netherlands, the effects are simply overwhelming. Since the outbreak began in 2007, 10 farm workers have died, thousands have been sick and tens of thousands of goats slaughtered.In other countries, the Q fever is not special in any way. It is simply an annual phenomenon. But it seems to have stayed in the Netherlands for reasons yet to be discovered. If it remains uncontrolled, many more humans and animals might suffer. Clearly, the future is in the hands of microbiologists privy to the disease. Is Q fever a local outbreak that can invade Europe? That is what FEMS Focus will try to clarify in this issue.

Tone Tønjum & Chared Verschuur

Editors

This rare disease is caused by infection of the bacterium Coxiella burnetii. This organism may be found in cattle and other domestic animals. It is a disease of worldwide distribution, however, per-ceived to be very uncommon.Usually an occupational hazard for cat-tle workers, Q fever is seemingly living up to its name when it infected thou-

April 2010 No. 7

Q fever was named as such because it was a mystery when first discovered in 1937 in Brisbane, Queensland, Australia. “Q” was primarily used for the word “query” but even when the bacterium that causes the disease was already determined, the name “Q fever” remained.

Q fever- the secret epidemic?

From the Editorial Team

sands of residents in the Netherlands in 2009 and caused the death of six people. What started as a harmless and control-led outbreak in a small town called Her-pen in 2007, led to the massive slaugh-ter of goats at the end of 2009. FEMS Focus found these events impor-tant in the microbiological world. So we

Didier Raoult, M.D., Ph.D. is a graduate of Marseille Medical School and performed internal medicine and infec-tious disease specialty training in the same institution. He received degrees in bac-teriology, virology and parasitology and obtained his Ph.D. in microbiology at Montpellier, France. Currently, he is a full Professor at Marseille School of Medicine and is Director of the Clinical Micro-biology Laboratory for the University Hos-pitals and President of the Universite de la Mediterranee. He is the co-founder of the European Study Group of Rickettsia, Ehrlichia, Coxiella (EUWOG) and the founder of the National Rickettsia Refer-ence Center, WHO Collaborative Center, the largest laboratory in the world in the field of Rickettsial diseases. He participat-ed in the first isolation of several bacteria and new Rickettsial diseases.

Prof. Roel Coutinho studied medi-cine in Amsterdam. His early career included a period working in Guinea-Bissau and Senegal. On his return to the Netherlands, he opted to specialize in medical microbiology and in 1977 became head of the Amsterdam Public Health Department, where he pioneered cohort studies into HIV and Aids. He earned a PhD in 1984. In 1989 he was appointed Professor of Epidemiol-ogy and Infectious Disease Control at the Academic Medical Centre in Amsterdam. In 2000, Prof. Coutinho was appointed Director of the Amster-dam Municipal Health Services, and in 2005 he became director of RIVM’s Centre for Disease Control. Roel Coutinho has written or co-authored over five hundred scientific articles and is editor of the journal AIDS.

took time to interview two experts in the field to put some light to the issue. Dr Didier Raoult is a leading infectious disease expert, co-found-er of the European Study Group of Rickettsia, Ehrlichia, Coxiella and founder of the National Rickettsia Reference Center, WHO Collabora-tive Center, which is the largest laboratory in the world in the field of Rickettsial diseases. Prof Roel Coutinho is the Director of the Cen-tre for Infectious Disease Control in the Neth-erlands, the government department dedicated to controlling the disease.

How widespread is Q fever worldwide? How many animals and humans are infected each year and what is the mortality rate? Didier Raoult (DR): Q fever is a zoonosis caused by the bacterial pathogen C. burnetii, and is seen throughout the world (except in New Zealand). In combination with poor diagnos-tics and lack of awareness, exact incidences and mortality rates are hard to define. The av-erage annual reported incidence is 0.28 cases per million persons. Currently, there are out-breaks in the Netherlands that have gained considerable numbers and public attention. However, this is not unique or new. Also, in many other places in Europe, there have re-cently been a number of large outbreaks that to a large extent have been neglected. In Swit-zerland in 1983, there have been 500 cases with 20 deaths; 3 outbreaks in Germany and one in Bulgaria in 2009.

Roel Coutinho (RC): Q fever in itself is wide-spread. It is generally seen as an occupational disease for people who handle goat and sheep or other animals and those most often con-tract pneumonia or hepatitis. If somebody gets pneumonia and he or she works with animals, then the doctor may think about Q fever and diagnose it. We have had several outbreaks in the world before but the mag-nitude of the outbreak in the Netherlands is unprecedented.

What is the nature of the C. burnetii strains causing the current outbreaks? What proper-ties are enabling the efficient spread?DR: Each Q fever outbreak is normally caused by one clonal strain. Usually, strains that are able to spread from goats to humans, most often by aerosols, cause disease in humans and elicit considerable outbreaks. Only about 104-105 bacteria are required to cause disease.

The spread is not from human to human, but from the same aerosol source, which can be quite efficient and in strong wind can spread over long distances, such as kilometers.RC: We have very good evidence that this is caused by intensive goat farming in the Netherlands which was not the situation in our country before. And so you have farms with some 1000 goats and sometimes more than that. What we saw is that they had abortion storms. After the abortion period, the bacteria survived and went airborne. If you look at farms where abortion storms oc-curred, for example, you can see that when you live 1 or 2 kilometers from a farm, you will have up to 30 times higher risk (of con-tacting Q fever) than the people living 5 kilometers away, so there is airborne trans-mission based on the abortion. C. burnetii is highly resistant. It forms a type of spores and these spores survive in the environment.

What new traits/phenotypes are occurring? How virulent is it?DR: The situation is not that a new C. bur-netii strain has arisen, but that the awareness is heightened. Recent studies have led to sub-stantial changes in the approach to its diag-nosis and treatment, enabling the detection of more cases. The increased awareness, along with better diagnostic tests, may explain the rising number of outbreaks of Q fever report-ed over the past 10 years worldwide. Once you start looking for Q fever, you’ll find more and more of it. The strains are probably the same, however, the new diagnostics and in-creased awareness now enable the detection of C. burnetii Q fever cases and outbreaks that otherwise might be over-looked.RC: There are several strains circulating in the world but there is no evidence that the strain that we currently have in the Netherlands is more pathogenic than the others. It is not easy to type the bacteria precisely. We have not been able to detect evidence of links be-tween the strains in the farm and the strains infecting humans around that farm with mo-lecular typing. What are the similarities / differences in the C. burnetii outbreaks in different parts of the world? Why is Q fever so widespread in the Netherlands?

RC: Apart from the intensive goat farming, preliminary data show that environmental conditions may have an effect on the out-break. Recent studies show that infective aerosols can travel several kilometers under dry and dusty conditions. In these datasets, the strongest correlation found was between the vegetation density and soil moisture. This makes sense because when it is dry, the bacteria are easily dispersed and transmitted. Farms that have more moisture on the other hand have lower human Q fever risk. Is C. burnetii still sensitive to antibiotics?DR: Tetracycline such as doxycycline is the drug of choice, although resistance to these antibiotics is growing rapidly.

If Q fever is spread from animals to human, is there also a possibility of a human to human spread?DR: No, this would be unlikely.RC: There are rare descriptions of human to human transmission in the literature. But this does not play a role in the spread. Is this the new weapon in biological warfare?DR: No, Q fever is really not efficient enough for bioterrorism. Mistakenly, in the United States and by the Centers for Disease Control (CDC), Q fever is classified as a “Category B” bioterrorism agent because it would be rela-tively easy to use, promoted by the events on 9-11. C. burnetii is now unduly considered a potential agent of bioterrorism. This is also

Scientific terms in this issueAerosol a colloid system in which solid or liquid particles are suspended in a gas, especially a suspension of a drug or other substance such as bacteria to be dispensed in a cloud or mistCoxiella burnetiia species of intracellular, pathogenic bacte-ria, that is the causative agent of Q feverClonalityarising from one single genetic lineageGram-negative bacteriabacteria that do not retain crystal violet dye in the Gram staining protocol

Pathogeniccausing diseasePleomorphican organism (single or within a species) that assumes various distinct formsRickettsialpertaining to or caused by rickettsiaeVirulencethe degree of pathogenicity of a microor-ganism as indicated by case fatality rates or its ability to invade the tissues of the hostZoonosisa disease of animals that is transmissible to humans under natural conditions

This tick specie is known to be a vector for Tick-borne encephalitis virus, caused by a member of the Tick-borne encephalitis virus complex, Flaviviridae, and Q fever, which is caused by the bacteria Coxiella burnetii. Credits: CDC/ Donated by the World Health Organization, Geneva, SwitzerlandQ Fever, Coxiella burnetti, is a disease passed to

humans from sheepCredits: CDC/ Dr. Edwin P. Ewing, Jr. because, although not as deadly as anthrax or

plague, attacks could still create widespread disease and panic.RC: It is on the list of biological agents but the Q fever outbreak here is due to intensive goat farming and has nothing to do with biologi-cal warfare. Will there be a vaccine soon? What is the im-pact of other preventive measures?DR: An urgent question is how to bring the outbreak under control. In 2008, veterinary and public health authorities hoped that hy-gienic measures, such as a ban on distribut-ing manure on farm fields, would help reduce human exposure. Now, the hope is that an animal vaccine produced by CEVA, a French company, can help bring the microbe under control. After short supplies in 2008 and 2009, the vaccine will be plentiful in 2010. The vaccine does not prevent all infections, but it does prevent most abortions, which should help curtail the spread of the disease. The vaccine does not work in infected ani-mals and based on trials in Australia, the cur-rent vaccine is not good enough, so there is further need for improved vaccine develop-ment.RC: There is a vaccine for animals and that is what we are using at the moment (Coxevac manufactured by CEVA). In addition, we have taken a large number of hygienic meas-ures for the farms. The available vaccine for animals does not completely protect against infection but there is very good evidence that

Only about one-half of all people infected with C. burnetii show signs of clinical illness. Most acute cases of Q fever begin with sudden onset of one or more of the following: high fevers (up to 104-105° F), severe headache, general malaise, myalgia, confusion, sore throat, chills, sweats, non-productive cough, nausea, vomiting, diarrhea, ab-dominal pain, and chest pain. Fever usually lasts for 1 to 2 weeks. Weight loss can occur and persist for some time. Thirty to fifty percent of patients with a symptomatic in-fection will develop pneumonia. Additionally, a majority of patients have abnormal results on liver function tests and some will develop clinical hepatitis. In general, most patients will recover to good health within several months without any treatment. Only 1%-2% of people with acute Q fever die of the disease. – www.cdc.gov

Spotting Q fever

• Q fever is caused by the obligate intracellular rickettsial agent C. burnetii• The organism is pleomorphic and has an envelope similar to that of gram-negative bacteria

• The organism is resistant to heat, drying and many common disinfectants

• The spore-like forms enable the bacteria to survive for long periods in the environment

Get to know Coxiella burnetii

it protects against abortion if given before a goat is infected or pregnant. All goats and sheep in the Netherlands will be vaccinated. There is also a vaccine for humans (Q-Vax) registered in Australia (but not in Europe or the US), but this vaccine is not suitable for mass vaccination. Our main effort right now is geared towards minimizing the exposure. The human vaccine may be given to persons with an occupational risk. We are now col-lecting all available data to see whether this may be an option.

What preventive measures are implemented in the Netherlands to control the spread of Q fever this coming spring when cattle give birth?RC: We have implemented a lot of measures to control the outbreak. It is difficult to predict how this is going to develop in the spring, or in the next few months. All pregnant goats have been culled this winter so there will not be any more abortions. But we also know that many bacteria are still in the environ-ment and it is therefore difficult to predict how the outbreak this year will evolve.

Does the Q fever outbreak in the Netherlands mean worse outbreaks in the future?DR: When Q fever is not common in the pop-ulation, there is no protective herd immunity and the population is rendered susceptible to an outbreak when the aerosol mediating the agent occurs. So in areas of the world where Q fever is uncommon, new outbreaks can occur, due to aerosol spread rather than new C. bur-netii strain development. Therefore, in New Zealand and Nordic countries such as Nor-way, Sweden and Denmark, outbreaks can be expected upon spread, as a global spread is also expected. In Denmark, Q fever is already detected after human contact with cattle. #

• Slaughter of around 40,000 goats at the end of 2009

• Compulsory vaccination of all sheep and goats before June 1, 2010

• Prohibition of goat and sheep breeding until July 1, 2010

• Regulation of visitors in farms

• Hygienic manure handling

Some preventive measurestaken to control Q fever in the Netherlands

Coxiella burnetii is the causative agent Q feverCredits: CDC/ Gilda Jones

The FEMS Focus is published by the FEMS Central Office. Whom to contact? Prof. Dr. Tone Tønjum (tone.tonjum@medisin.uio.no).Design & production: ilumina@ilumina.siFEMS is a registered charity (no. 1072117) and also a company limited by guarantee (no. 3565643). © 2010 Federation of European Microbiological Societies

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Following the increase of Q fever cases in humans reported in 2008 and in particu-lar in the last months of 2009 in some EU Member States, the European Commission asked European Food Safety Authority to provide urgent scientific advice to inform possible EU risk management measures in this area. EFSA’s Panel on Animal Health and Wel-fare (AHAW) will lead the work with the support of the Panel on Biological Hazard Panel (BIOHAZ) and in close collabora-

tion with the European Centre for Disease Prevention and Control (ECDC).A scientific opinion is expected by the end of April 2010. The Panel will look at the oc-currence and spread of Q-fever in farm ani-mals and humans across the EU, assess the risks factors related to the disease, as well as evaluate the effectiveness and efficiency of disease control options. These may in-clude vaccination, animal movement and biosecurity restrictions and pharmaceutical treatments. (source: www.efsa.europa.eu)

The EU strategy against Q feverNews from the European Commission

Thematic issue now available

A news story in the Netherlands pointed out that the Centre for Infectious Disease Control in the country claimed that it is expecting more Q fever patients this year. However, Dr Coutinho denied this by say-ing it is not to be predicted. He is positive that the culling of pregnant goats late last year (2009) and early this year (2010) will prevent C. burnetii-infected abortions this year. “However”, he said, “a large number of spores are still in the environment and could cause human cases around the farms with abortion storms before. It could also be that Q fever is now going to circulate

more widely in other animals which may also cause human cases.”He further assured both residents and tour-ists that the risk to contract Q fever is very low. “The risk is higher for persons living close to infected goat farms but even for that group, the risk remains very limited”, he maintained. Nonetheless, he advised people who have been in the area and de-veloped pneumonia to consult the doctor and inform about Q fever. “This is a very rare disease.” he said, “Doctors will normally not think about this possibility and thus will not ask the laboratory to test for it.” #

Q fever update

http://ecdc.europa.eu/en/healthtopics/Pages/Q_fever.aspxhttp://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19210http://www.efsa.europa.eu/en/ahawtopics/topic/qfever.htmhttp://en.wikipedia.org/wiki/Q_feverhttp://www.umm.edu/ency/article/001337.htmhttp://www.cdc.gov/ncidod/dvrd/qfever/http://www.nlm.nih.gov/medlineplus/ency/article/001337.htmhttp://www.idph.state.il.us/Bioterrorism/factsheets/qfever.htmhttp://news.bbc.co.uk/2/hi/8417009.stmhttp://www.eurosurveillance.org

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