April 2010 No. 7 NEWSLETTER OF FEMS
FEDERATION OF EUROPEAN MICROBIOLOGICAL SOCIETIES
Q feverthe secret epidemic? 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. 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, perceived to be very uncommon. Usually an occupational hazard for cattle workers, Q fever is seemingly living up to its name when it infected thou-
Didier Raoult, M.D., Ph.D. is a graduate of Marseille Medical School and performed internal medicine and infectious disease specialty training in the same institution. He received degrees in bacteriology, 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 Microbiology Laboratory for the University Hospitals 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 Reference Center, WHO Collaborative Center, the largest laboratory in the world in the field of Rickettsial diseases. He participated in the first isolation of several bacteria and new Rickettsial diseases.
sands of residents in the Netherlands in 2009 and caused the death of six people. What started as a harmless and controlled outbreak in a small town called Herpen in 2007, led to the massive slaughter of goats at the end of 2009. FEMS Focus found these events important in the microbiological world. So we
Prof. Roel Coutinho studied medicine in Amsterdam. His early career included a period working in GuineaBissau 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 Epidemiology and Infectious Disease Control at the Academic Medical Centre in Amsterdam. In 2000, Prof. Coutinho was appointed Director of the Amsterdam 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.
From the Editorial Team 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 giving birth. This also means a sudden burst of microbes in the air called Coxiella burnetii. 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
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-founder of the European Study Group of Rickettsia, Ehrlichia, Coxiella and founder of the National Rickettsia Reference Center, WHO Collaborative Center, which is the largest laboratory in the world in the field of Rickettsial diseases. Prof Roel Coutinho is the Director of the Centre for Infectious Disease Control in the Netherlands, 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 diagnostics and lack of awareness, exact incidences and mortality rates are hard to define. The average annual reported incidence is 0.28 cases per million persons. Currently, there are outbreaks 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 recently been a number of large outbreaks that to a large extent have been neglected. In Switzerland in 1983, there have been 500 cases with 20 deaths; 3 outbreaks in Germany and one in Bulgaria in 2009.
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 occurred, 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 contacting Q fever) than the people living 5 kilometers away, so there is airborne transmission based on the abortion. C. burnetii is highly resistant. It forms a type of spores and these spores survive in the environment.
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 collecting 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 environment and it is therefore difficult to predict how the outbreak this year will evolve.
Spotting Q fever
Q Fever, Coxiella burnetti, is a disease passed to humans from sheep Credits: CDC/ Dr. Edwin P. Ewing, Jr.
Roel Coutinho (RC): Q fever in itself is widespread. It is generally seen as an occupational disease for people who handle goat and sheep or other animals and those most often contract 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 magnitude of the outbreak in the Netherlands is unprecedented. Get to know Coxiella burnetii fever is caused by the obligate intracellular rickettsial • Qagent C. burnetii organism is pleomorphic and has an envelope • The similar to that of gram-negative bacteria organism is resistant to heat, drying and many • The common disinfectants spore-like forms enable the bacteria to survive for • The long periods in the environment What is the nature of the C. burnetii strains causing the current outbreaks? What properties 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.
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, abdominal 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 infection 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 What new traits/phenotypes are occurring? How virulent is it? DR: The situation is not that a new C. burnetii strain has arisen, but that the awareness is heightened. Recent studies have led to substantial changes in the approach to its diagnosis 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 reported 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 increased 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 between the strains in the farm and the strains infecting humans around that farm with molecular 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?
Some preventive measures taken to control Q fever in the Netherlands
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, Switzerland
RC: Apart from the intensive goat farming, preliminary data show that environmental conditions may have an effect on the outbreak. 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 relatively easy to use, promoted by the events on 9-11. C. burnetii is now unduly considered a potential agent of bioterrorism. This is also
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 biological warfare. Will there be a vaccine soon? What is the impact 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 hygienic measures, such as a ban on distributing 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 animals and based on trials in Australia, the current vaccine is not good enough, so there is further need for improved vaccine development. 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 measures for the farms. The available vaccine for animals does not completely protect against infection but there is very good evidence that
Coxiella burnetii is the causative agent Q fever Credits: CDC/ Gilda Jones
Slaughter of around 40,000 goats at the end of 2009 • Compulsory • June 1, 2010vaccination of all sheep and goats before of goat and sheep breeding until July 1, 2010 • Prohibition of visitors in farms • Regulation • Hygienic manure handling Does the Q fever outbreak in the Netherlands mean worse outbreaks in the future? DR: When Q fever is not common in the population, 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. burnetii strain development. Therefore, in New Zealand and Nordic countries such as Norway, 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. #
Scientific terms in this issue Aerosol 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 mist Coxiella burnetii a species of intracellular, pathogenic bacteria, that is the causative agent of Q fever Clonality arising from one single genetic lineage Gram-negative bacteria bacteria that do not retain crystal violet dye in the Gram staining protocol
Pathogenic causing disease Pleomorphic an organism (single or within a species) that assumes various distinct forms Rickettsial pertaining to or caused by rickettsiae Virulence the degree of pathogenicity of a microorganism as indicated by case fatality rates or its ability to invade the tissues of the host Zoonosis a disease of animals that is transmissible to humans under natural conditions
News from the European Commission
The EU strategy against Q fever Following the increase of Q fever cases in humans reported in 2008 and in particular 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 Welfare (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 occurrence and spread of Q-fever in farm animals 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 include vaccination, animal movement and biosecurity restrictions and pharmaceutical treatments. (source: www.efsa.europa.eu)
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Q fever update S FEM adlines e ts D ts Gran Gran e c n da Atten r 1, 2010 ings g n i t e Mee eptemb e at meet er 1, S b c ndan een Octo 11 e t t a for ng betw l 30, 20 i i open 10 – Apr 20 S FEM llowship e rch F 10 Resea ne 15, 20 u J
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 saying 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 tourists 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 developed 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 Links and Resources http://ecdc.europa.eu/en/healthtopics/Pages/Q_fever.aspx http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19210 http://www.efsa.europa.eu/en/ahawtopics/topic/qfever.htm http://en.wikipedia.org/wiki/Q_fever http://www.umm.edu/ency/article/001337.htm http://www.cdc.gov/ncidod/dvrd/qfever/ http://www.nlm.nih.gov/medlineplus/ency/article/001337.htm http://www.idph.state.il.us/Bioterrorism/factsheets/qfever.htm http://news.bbc.co.uk/2/hi/8417009.stm http://www.eurosurveillance.org
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.si FEMS 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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