Q-Fever - available
Control ToolsDiagnostics availabilityReady-to-use PCR kits are commercially available and can detect C. burnetti DNA in several samples. Only for veterinarian usage licensed. Ready-to-use ELISA kits are commercially available and can detect anti-phase II antibodies in human or both anti-phase I and II antibodies in ruminants (LSI, IDEXX,…) GAPS:
Yes.
None. GAP:
Methods are described in the OIE Manual of Diagnostic Tests and Vaccines for Terrestrial animals 2010 chapter 2.1.12 and include: 1.Identification of the agent a. Staining b. Specific detection methods: specific immunodetection (capture enzyme linked immunosorbent assay (ELISA), immunohistochemistry), in-situ hybridisation, or DNA amplification. Polymerase chain reaction (PCR) methods have been used successfully to detect C. burnetii DNA in cell cultures and biological samples. The real-time PCR provides an additional means of detection and quantification c. Isolation of the agent d. Genotyping methods: MLVA (multi-locus variable number of tandem repeats analysis) and multispacer sequence typing (MST) are two PCR-based typing methods, that permit the typing of C. burnetii without the need for isolation of the organism. 2. Serological tests a. Indirect immunofluorescence test b. Complement fixation test (not any longer useful in ruminant diagnostics because performances of ELISA) c. Enzyme-linked immunosorbent assay GAPS:
Variable with potential markets in those countries with high levels of infection. The initiative to develop new diagnostic kits will depend on awareness and the possible introduction of control measures as occurred in the Netherlands. GAP: Point-of-Care-Antigen-Test. Not available but could be required if extensive vaccination campaigns are introduced. Vaccination won`t eradicate the disease. GAP: Need for DIVA. There is an urgent need for the development of a molecular method for the assessment of bacterial viability, especially in environmental samples and milk samples. The development of a multiplex PCR e.g. with a DNA microarray constitutes another helpful technique for screening all infectious abortive agents.
MLVA genotyping is used in the investigations of the major outbreak in the Netherlands. Efforts to produce a standardised scheme for MLVA (based on common decisions for allele calling and marker panels to be used) are in progress. Identification of the agent using genotyping methods is useful to understand the transmission routes, distance and speed of spread (between source and humans, within and between herds).
A recent study on the humoral immune response to Coxiella burnetii infection by protein microarray identified nine differentially reactive antigens that were also validated on an alternative immunostrip platform, demonstrating proof-of-concept and the potential Development of a consistent, safe, and inexpensive diagnostic assay alternative. - Test to identify naïve animals (based on cellular immunity) GAPS:
Vaccines availabilitySeveral vaccines have been developed against animal Q fever but only phase I vaccine has revealed to be protective against a virulent challenge. GAPS: At present Coxevac is produced in a very small-scale. Human and veterinary vaccine availability is limited. There are two currently available vaccines (Coxevac, phase I, CEVA Santé Animale and Chlamyvax FQ, phase II, MERIAL), Coxevac only is efficient and is already in large scale use in France and has also been used in the Netherlands in goat herds. Coxevac vaccine is an inactivated phase I vaccine. It is not authorized and only available in particular condition in France and Netherlands, but application has been submitted. Coxevac vaccine is prepared with Nine Mile strain of C. burnetii in yolk sacs of pathogen-free embryonated hen eggs. The vaccine consists of purified formaldehyde inactivated phase I C. burnetii corpuscular antigens. GAPS: In most of the European countries, you have to import. No commercially available. Human vaccine is of limited availability. No. GAP: No DIVA system exists. No. As an obligate intracellular bacterium, C. burnetii can be grown only in embryonated eggs or cell cultures or, when necessary, in inoculated laboratory animals. Several inactivated vaccines against Q fever have been developed. Phase I vaccine was effective and prevented both abortion and stilbirth and reduced the shedding of C.burnetti in the milk, vaginal mucus and faeces in experimentally challenged goats In natural conditions, the vaccination of highly shedding goats herds had reduced the bacterial quantities shed, especially by the primiparous animals when vaccinated several months after be born.. In cattle herds, which were less infected, it reduced 5 times the risk of infection (and thus of shedding) for susceptible animal vaccinated when not pregnant. Repeated annual vaccination is recommended in heavily infected areas, particularly of young animals. Depending on the epidemiological risks, repeated annual vaccination in non or low infected herds/flocks should be sufficiently preventive against incidence of the infection. GAPS:
Commercial potential exists where disease is a problem and where there is a spill over into the human population. This is particularly the case in the Netherlands where infection in goats poses a severe problem. The development of combined vaccines with major abortive agent, such as Chlamydia (in goat and sheep) could be advantageous. GAP: Probably human vaccine dos not have market potential except in the Netherlands but development of a new, modern human vaccine is useful. Use of genetically modified vaccines might be problematic in some countries. Feasible to manufacture in P3 facilities. Possible to use on farms to prevent entry or spread and as a precautionary measure if Q fever is a problem in a region.
GAPS:
Pharmaceutical availabilityAntibiotics could be used. In animals antibiotics may suppress rather than eliminate infections and their efficacy needs to be evaluated. In humans the recommended regimen for acute Q fever associates doxycycline (200 mg daily for 14 days) to hydroxychloroquine (chronic disease), which alkalinizes the phagolysosomes. Fluoroquinolones are considered to be a reliable alternative and have been advocated for patients with Q fever meningoencephalitis, because they penetrate the cerebrospinal fluid. Cotrimoxazole and rifampin can be used in case of allergy to tetracyclines or contraindication. Erythromycin and other new macrolides such as clarithromycin and roxithromycin, could be considered a reasonable treatment for acute C. burnetii infection. On the other hand, treatment of the chronic form of Q fever still consist a therapeutic dilemma. Although the optimal duration of therapy is unknown, the current recommendations for the treatment of chronic Q fever are 100 mg of doxycycline orally twice daily with 600 mg of hydroxychloroquine by mouth once daily for at least 18 months. Serologic testing is recommended on a regular basis during therapy, and the main predictive criterion of clinical cure is a decrease of phase I IgG antibody titers to <200. When available, the C. burnetii strain should be cultured from blood or valves in order to evaluate the doxycycline MIC: the doxycycline plasmatic level should be adjusted between 1.5 and 2 MICs. There have been reports for isolation of C. burnetii from valves of Q fever patients following treatment for several months. In addition, there have been reports for isolates of C. burnetii resistant to doxycycline (MIC:8 μg/mL) from patients with Q fever endocarditis. GAPS: The parameters for treatment failures in chronic Q fever patients need to be further elucidated. More antibiotic agents need to be challenged against C. burnetii and their efficacy evaluated under phagolysosomal conditions. Additional methods need to be implemented capable of determining the MIC of doxycycline against C. burnetii from chronically infected Q fever patients without the prerequisite of bacterial isolation. No standard protocol for antibiotic resistance testing is available. Anti C.burnetti compounds or new antibiotics may become useful candidates Using current therapy, intracellular efficacy of tetracycline could be improved using a combination with chloroquine. Understanding the molecular mechanisms of C. burnetii antibiotic resistance will help our quest for developing better treatments. Two characteristics which are major prerequisites for the effectiveness of a new developed drug against C. burnetii are its ability to function in acidic ph and its high permeability within phagosomes. Elucidating the molecular mechanisms of C. burnetii at protein level underlying its intracellular life cycle will reveal new targets for the collapse of the bacterium’s parasitism. Limited. No specific issue. Anti-Coxiella compounds may become commercially interesting in the future.
New developments for diagnostic tests
GAPS:
In general the development of tests is much faster and less expensive than vaccine development. Time and cost depend on the nature of the test and time will elapse between development, validation and entry onto the market. Developing new tests is time consuming and labour intensive which adds to the costs. Costs cannot be specified as they will depend on the tests, basic researches required and the associated equipment and reagents.
Freedom from Q fever could only be certified by the development of tests which can confirm absence of infection with C.burnetti (sensitivity of 100%) and a better knowledge of the C. burnetii infection and shedding dynamics in various species and epidemiological circumstances. Modalities of sampling and analysis have to be defined for assessment of the intra-herd shedding prevalence and absence. Furthermore, methodologies for assessment of the environmental contamination have to be improved and validated. New developments for vaccinesSub-unit vaccines. Characterization of the vaccinal Nine Mile strain in order to identify specific serological markers and produce Monoclonal antibodies in view of a DIVA ELISA test development. GAPS:
A period of 5-10 years for the development, clinical trials and licensing is realistic. Very expensive but there could be a market for new vaccines which prevent infection and shedding of the organism if accompanied with a DIVA system. GAP: Impact of regulations on incidence of use.
GAP: Probably not protein-like protective antigens: difficulty in subunit antigen production. New developments for pharmaceuticalsPotential of anti-Coxiella substances needs to be researched and evaluated. Whole genome sequencing platform/database. Five to ten years is realistic. Expensive.
Disease detailsDescription and characteristics.Q fever is caused by the organism Coxiella burnetti which is a small pleomorphic gram-negative obligate intracellular cocobacillus. Sequencing of the first complete genome of C. burnetii has been achieved in 2004. This and 16S rRNA sequence analysis, have enabled Coxiella burnetii to be placed in the Coxiellaceae family in the order Legionellales of the gamma subdivision of Proteobacteria. According to ultrastructural studies, 3 distinct morphological forms have been described: the Large Cell Variant (LCV), which is the more metabolically and replicatively active form, while the Small Cell Variant (SCV) and the Small Dense Cell (SDC) or Spore Like Particle (SLP) are more dense forms. The LCV and some of the SCV are structurally Gram negative (outer membrane, lipopolysaccharide on the surface). The 3 forms represent different stages of a model of developmental cycle of C. burnetii. During the intracellular life cycle of C. burnetii, the bacterium transforms from SCV to the LCV form upon maturation of the phagosome. After its replication within the mature phagosome with the phagolysosomal characteristics, C.burnetii is transformed to the SCV form again. However, SCV of C. burnetii (even at low numbers) can be found during all stages of the intracellular life cycle of the bacterium. GAPS:
The lipopolysaccharide is of particular biological, medical and immunological significance. C. burnetii occurs as two antigenic forms: Phase I, isolated from infected animals or humans is highly pathogenic. Phase II which is obtained following propagation on cell culture or embryonated hen eggs is nearly avirulent or highly reduced in virulence. Whilst the two phases are morphologically identical, some of their biochemical characteristics including their lipopolysaccharide (LPS) composition differ. The Phase II is a truncated LPS of Phase I. The LPS Phase variation can be accompanied by a permanent chromosomal deletion that makes cell reversion from Phase II to Phase I impossible. The Phase II part of the LPS is more immunodominant than the Phase I specific part. In human medicine, the reference method for the serodiagnosis of Q fever is based on different serological profiles during the two forms of the infection: during acute Q fever, IgG and IgM antibodies are elevated against Phase II, whereas, during chronic Q fever, high levels of IgG and IgM antibodies to Phase I equal or higher than to Phase II of the bacteria are observed. Recently, the hypothesis that C. burnetii isolates are at different stages of pathoadaptation has been formulated after the sequencing of complete genomes of three C. burnetii strains and comparison with the Nine Mile reference strain. Moreover, while isolates contain novel genes, they also harbour disparate collections of virulence-associated pseudogenes that likely contribute to pathogenicity and different phenotypes. Epidemiological links between genotypes of isolates and host species, spatial and temporal or virulence variability are under investigation. GAPS:
Outside the animal the bacteria becomes a small, dense, long lasting spore-like form which is able to resist heat, osmotic shock, drying, high pressure, oxidation, ultraviolet light and many common disinfectants. This form of C. burnetii is dormant (no multiplication) and infectious. A Endospore could be seen on the ultrastructural level but it is unclear if it plays a role in the environmental life cycle of Coxiella It can then contaminate dust and be spread by wind for long distances These features enable the bacteria to survive for variable periods in the environment and be a source of infection and are therefore a main concern in the field of the disinfection means. The description of these resistance properties of C. burnetii has been mostly reported in old studies. Although information is lacking on factors that regulate C. burnetii morphological transition, developmental regulation of genes by the alternative sigma factor RpoS and nutritional status have been implicated. GAPS: The representativeness of the environmental samples and method of investigation of viability of C burnetii need to be studied and validated. The conditions of the outside environment which facilitate the sporulation and those who maintain the survival are not well known Species involvedComments NA A worldwide zoonosis in humans, most acute cases result in asymptomatic or influenza-like disease; severe disease including a chronical form which is very difficult to cure develops in a few patients. Some arthropod ectoparasites, such as ticks, could have a role as a vector. The bacterial carriage by ticks seems very variable and the risk of transmission can be associated to bites (mainly in animals) as well to aerosols contaminated by their excrements. GAPS:
Cattle, sheep, and goats are the primary reservoirs of C. burnetii. A herd of a certain size seems necessary to sustain infection in an animal population. C. burnetii is capable of multiplying in the gut cells of ticks and large numbers of the bacterium can be shed in tick faeces contaminating hides and wool which may be a source of infection for people and animals either by direct contact or after faeces have dried and been inhaled as airborne dust particles. There is consensus among public health and veterinary professionals that most of the human Q fever outbreaks are linked to small ruminants, abortion waves on large farms representing the major risk. However, infection has been noted in a wide variety of other animals, including other species in the vicinity of livestock (dogs of herds, rodents, migratory birds, …), which could play a role as secondary reservoirs. GAPS:
Description of infection & disease in natural hostsVery few organisms may be required to cause infection and it is possible that a single organism can cause infection in humans More recent studies have shown that high numbers of C. burnetii must be present in an aerosols ambiant in order to lead to pathological lesions, otherwise only a seroconversion is observed. Large numbers of organisms are found in the placenta, foetal fluids, aborted foetus, milk, urine and faeces. As well as symptomatic animals asymptomatic seropositive and seronegative animals, may shed organisms. The infection is often latent; the bacteria may be persistently shed into the environment, especially at the time of giving birth. Highest numbers of C. burnetii are found within diseased herds, where relevant proportions of animals excreted high quantities. While an epizootic event constitute the initial moment for transmission, the risk of transmission can last for a long time depending on the bacterial environmental persistency. Other species can sometimes constitute the origin of human infection (domesticated pets, pigeons, …). Dry tick faeces could be a special source. Infected ticks are probably most important in maintaining the whole cycle of C. burnetii Ticks may play a significant role in the transmission of C. burnetii among the wild vertebrates, especially in rodents, lagomorphs, and wild birds. Ticks expel heavy loads of C. burnetii with their faeces onto the skin of the animal host at the time of feeding. Dogs may be infected by consumption of placentas or milk from infected ruminants, and by the aerosol route. Anti-phase II antibody seroprevalence was found ranging from 7 to 53% among wild brown rat populations in the United Kingdom and perhaps wild rats may represent a major reservoir of C. burnetii from which domestic animals, especially cats, which are natural predators of these animals, may become contaminated/infected. GAPS:
Not applicable. Infection is usually asymptomatic but occasionally infections have been recorded as causing placentitis (inflammation of the placenta) and abortion generally occurring in late pregnancy, stillbirths and delivery of weak offspring in cattle, sheep and goats. Metritits and mastitis were recorded in cattle Generally, an epizooty emerge within a weakly- or non- infected herd. No clinical episode occurs the subsequent years within goats and sheep herds, and at a lesser extent within cattle herds. GAPS:
The incubation period is variable; maybe between one and eight weeks. GAPS: incubation period unknown. Low except the mortality of foetusat the time of abortions in late pregnancy. In some cases Q fever can cause abortion of almost all reproductive goats in a herd. GAPS: motality unknown (weak calf syndrome). C .burnetii infection persists for several years, and is probably life long. Sheep, goats and cows are mainly asymptomatic carriers, but can shed considerable numbers of organisms at parturition, especially during a large Q fever abortion outbreak, and intermittently in various secretions and excreta. Concomitant shedding into the milk, the faeces and the vaginal mucus may be rare. The vaginal shedding at the day of parturition may be the most frequent and contain the highest numbers of bacteria. Ticks carrying the infection may be another source. Although C. burnetii is found in lower numbers in the milk, faeces and the vaginal mucus of infected dairy animals, this type of shedding may persist for several months increasing the risk for bacterial transmission. Shedding kinetic patterns of C. burnetii in wild animals (e.g. foxes, moufflons-wild goats, hares) and migratory birds may contribute to the transmission of the bacterium. GAPS: Insufficient information on shedding kinetics in goat, sheep and cattle are available, especially in absence of clinical sign or delay of the abortion. There is no exact knowledge about “shedding” dynamics in pets. There is no adequate information on shedding kinetic patterns concerning wild animals and migratory birds. The principal lesion is a necrotizing placentitis with large numbers of organisms in trophoblasts. Lesions in aborted foetuses are rare (10%) and most consisting of inflammation in liver, lung and kidney. GAPS: Proteomic analysis-based methods used for the comparison between infected and non-infected C. burnetii cells could provide insights for the proteomic background of the pathogenicity mechanism of the bacterium. Zoonotic potentialComments NA Because the disease is underreported, scientists cannot reliably assess how many cases of Q fever have actually occurred worldwide. The current method for the diagnosis of Q fever in humans is based on serology (IFA, ELISA). The early diagnosis is still difficult. Furthermore, the clinical polymorphism and the high proportion of asymptomatic humans with Q fever contribute to the increased level of under-reporting of the disease. Improved surveillance methods and a world-wide C. burnetii epidemiology-based-database connecting the reference laboratories around the world could reduce the gap in our knowledge. GAPS:
Transmission to humans mainly occurs through the inhalation of contaminated aerosols. These originate from infected dust contaminated by dried placental material, birth fluids, and excreta of infected animals or exposure to amniotic fluid or placenta. Other risks include drinking unpasteurised milk (but no valid evidence) and contact with infected material which can enter via abrasions and the conjuctiva. Possibly, a natural immunisation occurs for rural population. Indeed, most Q fever outbreaks occurred in semi-urban areas, sickening people who have no contact with farms. The most likely animals reservoir were ruminants, but the bacteria may spread in the vicinity. A depressive immunological status is the major factor promoting chronic manifestations of Q fever along the life. One more risk of transmission of C. burnetii is via manure. Manure based on animal faeces is used as a bio-fertilizer in many countries. The turn of gardening using more bio-based products has left a gap on our knowledge on the risk of transmission of C. burnetii via manure. Although, manure is generally treated mainly for common pathogens this treatment is unknown whether it is sufficient for killing C. burnetii. Thus, high numbers of the bacterium from faeces (main component of manure) of infected animals and/or previously infected soil contained in the manure can become airborne through gardening and infect humans. GAPS:
Clinical symptoms as Q Fever may only be seen in around half of all people infected with C. burnetii. Infection is often self limiting but some patients may develop a flu-like illness with pneumonia and/or hepatitis occurring in 30 to 50 %. Most patients will recover within several months and without treatment. Mortality in humans can be 1%-2%. A chronic severe debilitating disease can occur in a small percentage of cases in particular in those with suppressed immune systems and pre-existing heart valve problems (e.g. endocarditis). A post Q fever syndrome of chronic fatigue is also recorded. Infection in pregnant women may occasionally cause abortion or premature birth. The main characteristic of Q fever is its clinical polymorphism, so that diagnosis can only be made by systematic tests. It is likely that factors such as the inoculum size, affect the expression of C. burnetii infection. High inocula are associated with over production of IL10 leading to chronic infection. Gender and age also affect the expression of C. burnetii infection. Men are more often symptomatic than women despite comparable exposure and seroprevalence Moreover, the prevalence of clinical cases in children significantly increases with age and symptomatic Q fever occurs more frequently in people older than 15 years. In addition the clinical outcome of the infection could be different according to the route of infection. GAPS: Factors influencing the clinical manifestations, the severity of the symptoms as well as the final outcome of Q fever (chronic vs acute) still remain gaps in our knowledge. Human to human transmission is rare. Transmission of Q fever to attendants during autopsies or infection from a patient to the hospital staff can occur. Sexual transmission of Q fever has been reported in humans. GAPS: The possibility of human to human transmission needs to be investigated. Impact on animal welfare and biodiversityLimited impact. GAPS:
None. GAP: Unknown. No. First time implemented in 2010 in the particular crisis in The Netherlands. GAP: No harmonized action in the EU. Geographical distribution and spreadFirst identified in Australia in 1935, Q fever has since then been found throughout the world with the exception of New Zealand. The disease is found in most areas where goats, sheep and cattle are kept. Endemic in many countries. Numerous outbreaks can occur and spread can be rapid under certain circumstances. Yes due to seasonality of small ruminant kidding or tick amplification. Higher seroprevalence is reported when time spent in stable increases. GAP: seasonal cycle could be investigated more accurately. Variable but can be rapid. GAP: Need to be investigated in several conditions (ruminant species, density of animals, type of animal husbandry, climate…. Spread by asymptomatic animals. Importance of wind and dryness Outbreaks have been reported following exposure to infected pigeon faeces. Thus birds could be a risk for transboundary potential of the disease. GAP: The role of wild animal including birds and cats needs to be investigated. Yes importance of wind and dryness. GAPS: Influence of dryness, humidity, temperature on pseudo-spore formation and survival of C burnetii needs to be studied. Yes dry weather conditions correlate typically with outbreaks. Yes, dryness favors the survival of C burnetii. Humidity increases the number of ticks but in infected tick-faeces dry climate favours the persistence of the bacterium. Route of TransmissionThe organism may be present in reproductive fluids of infected animals, e.g. sheep, at lambing, with infection of other animals occurring through inhalation of aerosols, or of dry tick and birds faeces or by ingestion of infected contaminated material as placentas, foetus…. GAP: Transmission within herd or between herds needs to be investigated according to the species and the different routes of transmission (introduction, environmental or only milk shedding, wind…) Q fever can also be spread by ticks which pass the bacteria from an infected to a susceptible animal. Faeces form infected animals contain the bacteria and can contaminate the environment. The bacteria are also shed in the milk of an infected animal. Seroconversion was observed by drinking non pasteurised infected milk. GAPS:
Outbreaks typically occur following a birth or abortion where the environment becomes contaminated with birthing fluids. Q fever may be an emerging infection, possibly related to climate changes. Topographic factors combined to meteorogical factors, such as a prewailing wind and dry weather, seem to have synergic effects. GAPS:
Detection and Immune response to infectionOnce a domestic ruminant is infected, C burnetii localizes in mammary glands, supramammary lymph nodes, placenta, and uterus, from which it may be shed in subsequent parturitions and lactations. GAP: The immunological and metabolic host response is still unknown except ab-production. CMI, that is more important in protection than humoral response is not sufficiently characterized. Development of antibodies Cell mediated immunity seems to be crucial for the elimination of the agent. Intradermal testing can be performed. Humoral response against Phase I and Phase II LPS provides information on the Q fever forms in humans. IgM response can inform on the recent infection or on the vaccination of an initially free Q fever animal. In ruminants, IgG1 and IgG2 isotypes could be of interest for discrimination of evolutive infection and convalescent state. GAP: Development of diagnostic tools based on CMI. Main means of prevention, detection and controlControl of the infection when required, would concentrate on management practices such as separation of animals, and hygiene measures.
GAPS: Valuable, cheap and friendly method to determine herd status are needed.
GAP: Efficacy of these measure still unknown. Human and vet diagnostic tools are distinct: Diagnosis could be made by direct isolation of the organism from tissues such as placenta, but in practice it is performed by detection of DNA specific for C. burnetii using one of several PCR protocols, or by immunohistochemical staining for the antigens. PCR technique is now recognised as the most sensitive method to detect C. burnetii. Real-time PCR provide a quantitative result. Although a threshold is not officially approved internationally, one should mention that a group of French experts has considered that abortion in ruminants should be considered due to C. burnetii when at least 104 bacteria per gram of placenta or vaginal swab are detected. In tissues or stomach content from aborted fetuses, the same group considered that a positive result by PCR is sufficient to diagnose Q fever as the origin of abortion. For pooled samples the proposed threshold is 103 bacteria per pool. These thresholds are indicative and may be revised especially if new scientific information becomes available A number of serologic tests are available; the most commonly used assays include indirect immunofluorescence, ELISA and complement fixation. The antibody occurrence indicates a past as well recent exposure to C. burnetii. It is well established that CF is weakly sensitive compared to ELISA and indirect immunofluorescence. Firstly, CFT failed to detect some cases when anti-complementary substances were present in the tested sera. Secondly, some antibodies were not revealed by CFT because of differences in ability of the IgG subclasses to activate the complement. In ruminants, only IgG1 antibodies are known to fix the complement in CFT. Moreover, CFT titers may be reduced because the presence of IgG2 and IgM antibodies can suppress complement fixation by IgG1 antibodies. ELISA should be preferable to IFA for practical reason. ELISA requires a single dilution of sera and can be automated. Serology may be more helpful in screening herds than in individual animals. Western Blots (not available on the market) could be more helpful in diagnosis of individual human specimens while PCR based methods seem adequate for animal screening. GAPS:
Animal vaccination has been used in areas where infections are common. Several vaccines are available in European Member States but only inactivated phase I Coxiella vaccines are efficient. GAP: Phase I vaccine: Its efficiency against multiple field isolates must be explored as well as the duration of immunity and the determination of target population for vaccination (susceptible animals) Prophylactic treatment is sometimes recommended to reduce the risk of abortion and the excretion of C.burnetti shed by infected females while increasing the possibility for the development of antibiotic resistant C. burnetii strains. GAPS:
In the laboratory, strict controls are needed and C burnetii is to be handled under biosafety level 3 standards, In the farm, precautions should be taken into account during kidding:
Limited value due to the airborne transmission of Q fever. GAP: Sampling and testing procedure to define a flock/herd as Coxiella-free need to be established. In a C. burnetii-free flock, introduction of new stock should be minimized, or previously vaccinated, and contact with wildlife should be prevented as much as possible. Appropriate tick control should also be practiced. Prevention may be difficult, as the causative agent can also be introduced on fomites or in aerosols over long distances. GAPS:
The implementation, development and standardization of schemes for the monitoring and reporting of Q fever in animals are crucial for the prevention and control of this zoonosis. Propositions by EFSA have been elaborated to improve the reporting and to provide and establish comparable data on the occurrence of Q fever in the main animal reservoirs, taking into account the characteristics of Q fever, the traits of the bacterium, the situation of Q fever in most Member States, the availability of the suitable diagnostic tools and a financial compromise. A passive surveillance system should be preferable to active surveillance. This scheme is based upon identification of clinically affected herds (i.e. in which a series of abortion has occurred) by using laboratory-based diagnostic of Q fever. To screen large numbers of animals in a herd or flock, the most used method is serology. Serology can be used for screening herds but not to determine a Q fever status in individual animals. At group level, significant association was found between ELISA and an indirect immunofluorescent results and Q fever abortion as well as positive shedding via vaginal and fecal routes of goats from clinically affected herds. Complement fixation tests exhibit poor sensitivity and are not suitable for serological investigation of Q fever dynamics. PCR screening of milk, vaginal swabs could also be done. However, PCR testing should be done at different times and with different types of samples in order to do not miss shedding animals. Bulk tank milk testing by PCR and antibody ELISA is the most accurate sample for monitoring C burnetii infection in dairy herds. In the Netherlands, where dairy goats are incriminated in a large human outbreak, it is hoped that a new test, in which a sample of bulk tank milk coming from farms is PCR-tested for traces of the bacteria, will lead to the discovery of the at risk farms. Similarly in the case of investigation of non dairy herds, the possibility to test pools of individual samples, such as vaginal swabs or/and milk samples, should be considered. GAPS:
Vaccination with Phase I vaccine has been effective in cattle, goats and sheep and has reduced clinical problems as well as reducing shedding of the organism but is not eradicating the disease/organism. In Slovakia, the decrease in the occurrence of human and animal Q fever was suggested as the result of the large-scale vaccination of cattle that was carried out there over a 10 year period, together with improved veterinary control of domestic animal transport within the country. In the Netherlands, a large vaccination programme in goat and sheep farms has been implemented, the controlled processing of manure and checks on animal transports, but it is not clear yet whether bacterial shedding by animals is prevented or at least reduced by vaccination. Controlling the epidemic is difficult and can be compromised by the prolonged stability of the bacterium in the environment and the possible role of animal species other than small ruminants. In other countries, no large scale vaccinations for C. burnetii have taken place up to date. However in Greece, brucellosis eradication programmes have been shown helpful for the reduction of C. burnetii infected animals. The complementary to the vaccination measures undertaken for the control/prevention of animal brucellosis such as controlled slaughtering, improved farm hygiene (including the appropriate disposal of placentas after birth), restriction and control of trade and movement of animals obviously helps not only the reduction of brucellosis, but of many more zoonoses one of which is coxiellosis GAPS:
Cost of sanitary measures, treatment and vaccination. GAPS:
Disease information from the OIEYes. http://www.oie.int/fileadmin/Home/eng/Media_Center/docs/pdf/Disease_cards/Q-FEVER-EN.pdf None. http://www.oie.int/fileadmin/Home/eng/Health_standards/tahm/2.01.12_Q-FEVER.pdf Socio-economic impactComments NA Unknown but long-term treatment of the chronic cases (between 2 years to lifelong) has to be considered and incites to implement a surveillance of excess of acute cases and to limit an outbreak expansion as rapidly as possible. Variable. Direct impact due to abortions. A survey over 8 years (1991 – 1998) of 221 cases of caprine abortion in southern California reported that C.burnetii was the second most commonly diagnosed cause (9%) of reproductive wastage after Chlamydophila abortus (14%). Studies with controversial results about effect on fertility exists but the study design not very convincing. GAP: Real economic impact unknown and has to be studied. Costs of controls and vaccination are applied. GAPS: Cost when Culling of animals applied. Cost of containment. Limited. GAPS:
Trade implicationsNone. No international standards laid down in the OIE Terrestrial Animal Health code 2009. GAP: to define. None. GAP: to define. Limited due to possible restrictions on movements from known infected herds. GAP: to define. Main perceived obstacles for effective prevention and control
GAPS:
Main perceived facilitators for effective prevention and control
GAP: Increase knowledge on patho-mechanism and pathogenesis. RiskQ fever is a potential biological warfare agent being very infectious and very durable in the environment as well as capable of windborne spread. Risks are at least linked to the different sources and routes involved for the transmission which are not well known. Assessment of infectious dose in natural conditions needs to be further studied. Some reports suggested that a great quantity of bacteria in the ambient vicinity is required to be infective and induce pathological lesions. Moreover, the distances of windborne spread has to be better defined. GAP: No knowledge on “background”-levels of Coxiella in the environment in the different regions/countries. ConclusionDue to the outbreaks in Humans in the Netherlands during 2007-2009 a series of measures were introduced. Q fever has become a major public health problem in the Netherlands with 2,357 human cases notified in the year 2009. Since December 2009, drastic measures have been implemented, including the large-scale culling of pregnant goats on infected farms. The veterinary interventions, especially vaccination, animal movement restrictions, culling and hygiene measures are expected to have an impact in 2010 and 2011. For 2009 these are: 1. Restrictions for infected farms
2. Notification obligation for goat and sheep farms in case of high abortion rates
3. Compulsory vaccination of “high risk” goat and sheep farms of the Netherlands 4. Voluntary vaccination in the rest of the Netherlands 5. Hygiene protocol, which is in part mandatory 6. Extra research 7. Culling of all pregnant goats 8. So far, there are no signs that the Q fever problem is spreading to neighbouring countries. It could be that factors such as lower population density, lower animal density, and different animal production methods in Belgium and Germany, compared to the Netherlands, play a role. |
