Suspected Q fever in my flock or herd – which measures should I take as owner?

 Q fever is a notifiable animal disease and a zoonosis caused by the bacterium Coxiella (C.) burnetii. In particular, the pathogen is transferred by birth fluids and the afterbirth of infected sheep/goats and is a risk for human and animal health. If there is shedding of the bacterium by animals, it is important to prevent further spreading to other animals and humans in particular.

An infection with C. burnetii can be asymptomatic especially in sheep. Thus, an early detection of the pathogen in the flock/herd is often difficult for livestock owners.

Therefore, it is even more important to take the following Q fever symptoms in ruminants seriously:

Abortion and stillbirth 
 Birth of weak lambs/kids/calves
Retarded expulsion of the afterbirth

In the event of a suspected case your veterinarian can initiate diagnostics for Q fever. The most sensitive and meaningful test for verifying a C. burnetii infection is direct detection of gene material (DNA) of the pathogen by means molecular analysis of afterbirth material, dead lambs/kids/calves, vaginal swabs or preputial swabs.

At least the following measures should be taken when Q fever occurs in your flock/herd:

• Make sure births and shearing occur in closed premises.

• Store all after birth material immediately in a closed container until it is disposed of by animal by-products processing plants (rendering plants). The container should be cleaned and disinfected after having been emptied.

• Clean and disinfect your working clothes as well as your working material.

• Inform your colleagues and family members about necessary protective and hygiene measures.

• Post a sign near your stables: „Valuable livestock – Do Not Enter. Authorized Personnel Only."

• Prevent non-authorized people from getting access to your animals.

• Don't offer raw milk or raw milk products to consumers and stand down from drinking raw milk and eating raw milk products.

• Important: The process of pasteurisation results in inactivation of the pathogen.

• Store the dung for 9 months underneath foil as well as apart from any population, before you spread it on the fields.

• Have your herd/flock vaccinated against C. burnetii.

Tip (Germany): Please consult your Animal Diseases Fund (Tierseuchenkasse) for support for vaccination costs.

For further information please read our FAQs.

Q Fever was agreed on the list of 10 prioritised pathogens by EFSA:

 Prioritisation of zoonotic diseases for coordinated surveillance systems under the One Health approach for cross‐border pathogens that threaten the Union

In the context of the initiative ‘CP‐g‐22‐04.01 Direct grants to Member States’ authorities', EFSA was requested to develop and conduct a prioritisation of zoonotic diseases, in collaboration with Member States, to identify priorities for the establishment of a coordinated surveillance system under the One Health approach.

The methodology developed by EFSA's Working Group on One Health surveillance was based on a combination of multi‐criteria decision analysis and the Delphi method. It comprised the establishment of a list of zoonotic diseases, definition of pathogen‐ and surveillance‐related criteria, weighing of those criteria, scoring of zoonotic diseases by Member States, calculation of summary scores, and ranking of the list of zoonotic diseases according to those scores.

Results were presented at EU and country level. A prioritisation workshop was organised with the One Health subgroup of EFSA's Scientific Network for Risk Assessment in Animal Health and Welfare in November 2022 to discuss and agree on a final list of priorities for which specific surveillance strategies would be developed. Those 10 priorities were Crimean‐Congo haemorrhagic fever, echinococcosis (both E. granulosus and E. multilocularis), hepatitis E, influenza (avian), influenza (swine), Lyme borreliosis, Q‐fever, Rift Valley fever, tick‐borne encephalitis and West Nile fever. ‘Disease X' was not assessed in the same way as other zoonotic diseases on the list, but it was added to the final list of priorities due to its relevance and importance in the One Health context.
© European Food Safety Authority

Source: EFSA Journal 2023;21(3)

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Impact of Coxiella burnetii vaccination on humoral immune response, vaginal shedding, and lamb mortality in naturally pre-infected sheep

Introduction: Sheep are considered to be one of the main reservoirs for Coxiella burnetii, a gram-negative bacterium with high zoonotic potential. Infected sheep shed tremendous amounts of the pathogen through birth products which caused human Q fever epidemics in several countries. Information about the impact of an inactivated C. burnetii Phase I vaccine on humoral immune response, vaginal shedding, and lamb mortality in naturally pre-infected sheep is scarce.

Methods: Two identically managed and naturally C. burnetii-infected sheep flocks were examined for two lambing seasons (2019 and 2020). One flock (VAC) received a primary vaccination against Q fever before mating and the second flock served as control (CTR). In each flock, one cohort of 100 ewes was included in follow-up investigations. Serum samples at eight different sampling dates were analyzed by C. burnetii phase-specific ELISAs to differentiate between the IgG Phase I and II responses. Vaginal swabs were collected within three days after parturition and examined by a C. burnetii real-time PCR (IS1111). Lamb losses were recorded to calculate lamb mortality parameters.

Results: After primary vaccination, almost all animals from cohort VAC showed a high IgG Phase I response up until the end of the study period. In cohort CTR, the seropositivity rate varied from 35.1% to 66.3%, and the Phase I and Phase II pattern showed an undulating trend with higher IgG Phase II activityduring both lambing seasons. The number of vaginal shedders was significantly reduced in cohort VAC compared to cohort CTR during the lambing season in 2019 (p < 0.0167). There was no significant difference of vaginal shedders in 2020. The total lamb losses were low in both cohorts during the two investigated lambing seasons (VAC 2019: 6.8%, 2020: 3.2%; CTR 2019: 1.4%,2020: 2.7%).

Discussion: Neither the C. burnetii vaccine nor the C. burnetii infection seem to have an impact on lamb mortality. Taken together, the inactivated C. burnetii Phase I vaccine induced a strong IgG Phase I antibody response in naturally pre-infected sheep. It might also reduce vaginal shedding in the short term but seems to have little beneficial impact on lamb mortality.

Source: Bauer et al., Frontiers in Veterinary Science 01 frontiersin.org, 10.3389/fvets.2022.1064763

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TGF-β/IFN-γ Antagonism in Subversion and Self-Defense of Phase II Coxiella burnetii-Infected Dendritic Cells

 Dendritic cells (DCs) belong to the first line of innate defense and come into early contact with invading pathogens, including the zoonotic bacterium Coxiella burnetii, the causative agent of Q fever. However, the pathogen-host cell interactions in C. burnetii-infected DCs, particularly the role of mechanisms of immune subversion beyond virulent phase I lipopolysaccharide (LPS), as well as the contribution of cellular self-defense strategies, are not understood. Using phase II Coxiella-infected DCs, we show that impairment of DC maturation and MHC I downregulation is caused by autocrine release and action of immunosuppressive transforming growth factor-β (TGF-β). Our study demonstrates that IFN-γ reverses TGF-β impairment of maturation/MHC I presentation in infected DCs and activates bacterial elimination, predominantly by inducing iNOS/NO. Induced NO synthesis strongly affects bacterial growth and infectivity. Moreover, our studies hint that Coxiella-infected DCs might be able to protect themselves from mitotoxic NO by switching from oxidative phosphorylation to glycolysis, thus ensuring survival in self-defense against C. burnetii. Our results provide new insights into DC subversion by Coxiella and the IFN-γ-mediated targeting of C. burnetii during early steps in the innate immune response.

Source: Matthiesen S, Christiansen B, Jahnke R, Zaeck LM, Karger A, Finke S, Franzke K, Knittler MR. Infect Immun. 2023 Jan 23:e0032322. doi: 10.1128/iai.00323-22. Online ahead of print. PMID: 36688662

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The European Union One Health 2021 Zoonoses Report

 Q Fever – Key Facts

•  In 2021, the number of confirmed cases of human Q fever was 460 corresponding to an EU notification rate of 0.11 per 100,000 population. This is a decrease of 12.0% compared with the rate in 2020 (0.12 per 100,000 population).
• Compared with the rate before the COVID-19 pandemic (2017–2019 annual mean), there was a decrease of 38.8% and 45.8% with or without data from the United Kingdom.
• Over the past 5 years (2017–2021), a significant decreasing trend (p < 0.05) in the number of Q fever cases was observed.
• In 2021, Q fever cases occurred from April to September, in line with the spring/summer seasonal pattern. Cases were highest for the 50–55 years age group.
• In animals, cattle and small ruminants were mostly sampled during clinical investigations and passive monitoring of animals suspected to be infected with Coxiella burnetii. However, in the absence of harmonised reporting data in animals in the EU, the data reported to EFSA cannot be used to analyse spatial representativeness and trends over the years for Q fever at the EU level or to compare differences among reporting countries.
• In total, 17 MSs (15 in 2020) and five non-MSs (six in 2020) reported 2021 data for
  C. burnetii. The proportion of positive animals with direct tests was 5.9% in sheep (8.7% in 2020), 16.5% in goats (11.3% in 2020) and 5.2% in cattle (3.8% in 2020).The proportion of positive herds with direct tests was 4.1% in sheep (1.4% in 2020), 2.0% in goats (1.2% in 2020) and 4.8% in cattle (6.7% in 2020). The proportion of seropositive animals was 10.3% in sheep (11.4% in 2020), 24.6% in goats (25.0% in 2020) and 12.2% in cattle (9.6% in 2020). The proportion of seropositive herds was 18.9% in sheep (5.9% in 2020), 50.0% in goats (78.7% in 2020) and 15.1% in cattle (14.4% in 2020). Results from various other domestic
  and wild animal species were reported and only Italy reported positive results, mainly from dogs (73.2% out of 541) and water buffalos (4.7% out of 43).

Adapted from European Union One Health 2021 Zoonoses Report, © European Food Safety Authority

EFSA Journal 2022;20(12):7666, DOI: https://doi.org/10.2903/j.efsa.2022.7666
Author: European Food Safety Authority and European Centre for Disease Prevention and Control (EFSA and ECDC), Q Fever, p. 222 – 230, published 13th December 2022

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Surveillance of Coxiella burnetii Shedding in Three Naturally Infected Dairy Goat Herds after Vaccination, Focusing on Bulk Tank Milk and Dust Swabs

Q fever outbreaks on three dairy goat farms (A–C) were monitored after the animals had been vaccinated with an inactivated Coxiella burnetii phase I vaccine. The antibody response was measured before vaccination by serum samples with two C. burnetii phase-specific ELISAs to characterize the disease status. Shedding was determined by vaginal swabs during three kidding seasons and monthly bulk tank milk (BTM) samples. Dust swabs from one windowsill of each barn and from the milking parlors were collected monthly to evaluate the indoor exposure.

These samples were analyzed by qPCR. The phase-specific serology revealed an acute Q fever infection in herd A, whereas herds B and C had an ongoing and past infection, respectively. In all three herds, vaginal shedders were present during three kidding seasons. In total, 50%, 69%, and 15% of all collected BTM samples were C. burnetii positive in herds A, B, and C, respectively. Barn dust contained C. burnetii DNA in 71%, 45%, and 50% of examined swabs collected from farms A, B, and C, respectively. The largest number of C. burnetii positive samples was obtained from the milking parlor (A: 91%, B: 72%, C: 73%), indicating a high risk for humans to acquire Q fever during milking activity.

Abstract taken from: Benjamin U Bauer, Clara Schoneberg, T Louise Herms, Martin Runge, Martin Ganter, Surveillance of Coxiella burnetii Shedding in Three Naturally Infected Dairy Goat Herds after Vaccination, Focusing on Bulk Tank Milk and Dust Swabs, Vet Sci. 2022 Feb 24;9(3):102. doi: 10.3390/vetsci9030102.

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Q fever expertise among human and veterinary health professionals in Germany – A stakeholder analysis of knowledge gaps

Q fever is a zoonosis caused by Coxiella burnetii. In Germany, the common sources of human infections include small ruminants that excrete the pathogen. Q fever in humans can be asymptomatic or nonspecific. However, severe disease progression is also possible, which can lead to death. Q fever in small ruminants is usually asymptomatic, although reproductive disorders may occur. To protect humans from Q fever, it is important that human and veterinary health professionals (practitioners/health authority employees) have comprehensive knowledge of the diagnosis, control and prevention of Q fever, and its zoonotic potential. To ensure and enhance this understanding, this stakeholder analysis assessed Q fever expertise in human and veterinary health professionals in Germany and investigated how these knowledge gaps can best be resolved.

For this purpose, an online survey and two focus group discussions were conducted with 836 and 18 participants, respectively. Knowledge gaps are due to a lack of awareness of Q fever, especially among human health practitioners. Moreover, colleagues who have heard about Q fever still lack the necessary cross-species knowledge to successfully diagnose, control and prevent this zoonosis. Additionally, differences exist between stakeholders regarding their work context and the region in which they work. In this study, stakeholders in southwestern Germany had slightly better Q fever knowledge than their colleagues in North-eastern Germany.

In addition, information sources aimed at resolving knowledge gaps involve direct conversations between the stakeholders, as well as reading materials and seminars. Each of these information sources should focus on interdisciplinary resources to strengthen the cooperation between human and veterinary health professionals and to raise awareness of the strengths of each stakeholder group. These results have already been implemented by the Q-GAPS project, with goals of raising awareness of Q fever and filling knowledge gaps.

Abstract taken from: Fenja Winter und Amely Campe, A stakeholder analysis of knowledge gaps, PLoS One, 2022 Mar 3;17(3):e0264629.

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The Coxiella burnetii T4SS effector protein AnkG hijacks the 7SK small nuclear ribonucleoprotein complex for reprogramming host cell transcription

Inhibition of host cell apoptosis is crucial for survival and replication of several intracellular bacterial pathogens. To interfere with apoptotic pathways, some pathogens use specialized secretion systems to inject bacterial effector proteins into the host cell cytosol. One of these pathogens is the obligate intracellular bacterium Coxiella burnetii, the etiological agent of the zoonotic disease Q fever.

In this study, we analyzed the molecular activity of the anti-apoptotic T4SS effector protein AnkG (CBU0781) to understand how C. burnetii manipulates host cell viability. We demonstrate by co- and RNA-immunoprecipitation that AnkG binds to the host cell DExD box RNA helicase 21 (DDX21) as well as to the host cell 7SK small nuclear ribonucleoprotein (7SK snRNP) complex, an important regulator of the positive transcription elongation factor b (P-TEFb). The co-immunoprecipitation of AnkG with DDX21 is probably mediated by salt bridges and is independent of AnkG-7SK snRNP binding, and vice versa. It is known that DDX21 facilitates the release of P-TEFb from the 7SK snRNP complex.

Consistent with the documented function of released P-TEFb in RNA Pol II pause release, RNA sequencing experiments confirmed AnkG-mediated transcriptional reprogramming and showed that expression of genes involved in apoptosis, trafficking, and transcription are influenced by AnkG. Importantly, DDX21 and P-TEFb are both essential for AnkG-mediated inhibition of host cell apoptosis, emphasizing the significance of the interaction of AnkG with both, the DDX21 protein and the 7SK RNA. In line with a critical function of AnkG in pathogenesis, the AnkG deletion C. burnetii strain was severely affected in its ability to inhibit host cell apoptosis and to generate a replicative C. burnetii-containing vacuole. In conclusion, the interference with the activity of regulatory host cell RNAs mediated by a bacterial effector protein represent a novel mechanism through which C. burnetii modulates host cell transcription, thereby enhancing permissiveness to bacterial infection.

Source: PLoS Pathogens 18 (2022)

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Inactivation kinetics of Coxiella burnetii during high-temperature short-time pasteurization of milk:

 The Gram-negative, obligate intracellular bacterium Coxiella burnetii is the causative organism of the zoonosis Q fever and is known for its resistance toward various intra and extracellular stressors. Infected ruminants such as cattle, sheep, and goats can shed the pathogen in their milk. Pasteurization of raw milk was introduced for the inactivation of C. burnetii and other milk-borne pathogens. Legal regulations for the pasteurization of milk are mostly based on recommendations of the Codex Alimentarius. As described there, C. burnetii is considered as the most heat-resistant non-sporeforming bacterial pathogen in milk and has to be reduced by at least 5 log10-steps during the pasteurization process. However, the corresponding inactivation data for C. burnetii originate from experiments performed more than 60 years ago. Recent scientific findings and the technological progress of modern pasteurization equipment indicate that C. burnetii is potentially more effectively inactivated during pasteurization than demanded in the Codex Alimentarius. In the present study, ultra-high heat-treated milk was inoculated with different C. burnetii field isolates and subsequently heat-treated in a pilot-plant pasteurizer. Kinetic inactivation data in terms of D- and z-values were determined and used for the calculation of heat-dependent log reduction. With regard to the mandatory 5 log10-step reduction of the pathogen, the efficacy of the established heat treatment regime was confirmed, and, in addition, a reduction of the pasteurization temperature seems feasible.

Source: Marcel Wittwer, Philipp Hammer, Martin Runge, Peter Valentin-Weigand, Heinrich Neubauer, Klaus Henning und Katja Mertens-Scholz, Inactivation kinetics of Coxiella burnetii during high-temperature short-time pasteurization of milk
Frontiers in Microbiology, Vol. 12, 2022

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Cover story: A Q fever outbreak on a mixed dairy farm – a one health approach

 A Q fever outbreak on a dairy goat/cattle farm was investigated with regard to the One Health concept. Samples from all domestic animals and the farmer's family were collected, including goats with different reproductive statuses. The serological analysis revealed current infections in goats, whereas cows had ongoing infections. The possible influence of gestation and hormonal status on Coxiella burnetii infection in goats is discussed. A new cattle-associated Coxiella burnetii genotype C16 was identified in vaginal swabs and placentas from ruminants. Feline, canine, and human sera also tested positive for Coxiella burnetii antibodies. We conclude that the cattle herd may have transmitted Coxiella to the pregnant goats, resulting in zoonotic spread of Q fever to cats, dogs, and humans on the affected farm.

Source: Benjamin U. Bauer, Michael R. Knittler, T. Louise Herms, Dimitrios Frangoulidis, Svea Matthiesen, Dennis Tappe, Martin Runge and Martin Ganter
Cover story: A Q Fever Outbreak in a Mixed Dairy Farm - A one Health Approach
Publikation: Multispecies Q Fever Outbreak in a Mixed Dairy Goat and Cattle Farm Based on a New Bovine-Associated Genotype of Coxiella burnetii
Vet. Sci., Volume 8, Issue 11 (November 2021)

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