Coxiella burnetii infection persistence in a goat herd during seven kidding seasons after an outbreak of abortions: the effect of vaccination.

Coxiella burnetii infection was monitored during seven kidding seasons (2017-2023) in a dairy goat herd that after an outbreak of Q fever abortions was vaccinated with an inactivated phase I vaccine. Due to the high infection rate just after the outbreak, only the replacement stock was vaccinated during the first three kidding seasons, and when the average herd immunity had decreased (fourth kidding season onwards), the whole herd was vaccinated. Vaginal swabs, feces, and milk were analyzed by PCR to monitor infection, and dust and aerosols were analyzed to measure C. burnetii environmental contamination. One year after the onset of the outbreak, a significant reduction in C. burnetii shedding loads was observed, but the percentage of shedding animals remained high until the third kidding season. By the seventh kidding season, no shedders were detected. The bacterial load excreted was significantly lower in vaccinated compared with unvaccinated animals, and in yearlings compared with multiparous. C. burnetii was detected by PCR in aerosols collected inside the animal premises throughout the study period except in the last season; whereas, aerosols collected outdoors tested negative in the last three kidding seasons. Viable C. burnetii was detectable in environmental dust collected inside the barn until the third kidding season following the outbreak. These results indicate that after an outbreak of Q fever, the risk of infection for humans and susceptible animals can remain high for at least three kidding seasons when the number of C. burnetii animal shedders is still high, even when bacterial excretion is low. IMPORTANCE: Q fever is a zoonosis distributed worldwide. Ruminants are the main reservoir, and infection can cause high rates of abortion. After entering a farm, Coxiella burnetii infection can persist in the animal population over several lambing/kidding periods. Once infection is established in a herd, vaccination with the inactivated Phase I vaccine significantly reduces bacterial shedding, but although at low levels, excretion may continue to occur for several lambing/kidding seasons. The time that C. burnetii remains viable in the farm environment after an outbreak of Q fever determines the period when risk of infection is high for the people in close contact. This work showed that this period extends at least three kidding seasons after the outbreak. These results provided valuable information on the epidemiology of C. burnetii infection in goat herds and may help to develop guidelines for controlling the disease and reducing infection risk for susceptible people and animals.

Interdisciplinary studies on Coxiella burnetii: From molecular to cellular, to host, to one health research.

The Q-GAPS (Q fever GermAn interdisciplinary Program for reSearch) consortium was launched in 2017 as a German consortium of more than 20 scientists with exceptional expertise, competence, and substantial knowledge in the field of the Q fever pathogen Coxiella (C.) burnetii. C. burnetii exemplifies as a zoonotic pathogen the challenges of zoonotic disease control and prophylaxis in human, animal, and environmental settings in a One Health approach. An interdisciplinary approach to studying the pathogen is essential to address unresolved questions about the epidemiology, immunology, pathogenesis, surveillance, and control of C. burnetii. In more than five years, Q-GAPS has provided new insights into pathogenicity and interaction with host defense mechanisms. The consortium has also investigated vaccine efficacy and application in animal reservoirs and identified expanded phenotypic and genotypic characteristics of C. burnetii and their epidemiological significance. In addition, conceptual principles for controlling, surveilling, and preventing zoonotic Q fever infections were developed and prepared for specific target groups. All findings have been continuously integrated into a Web-based, interactive, freely accessible knowledge and information platform (www.q-gaps.de), which also contains Q fever guidelines to support public health institutions in controlling and preventing Q fever. In this review, we will summarize our results and show an example of how an interdisciplinary consortium provides knowledge and better tools to control a zoonotic pathogen at the national level.

Engineering Protein Nanoparticles Functionalized with an Immunodominant Coxiella burnetii Antigen to Generate a Q Fever Vaccine.

Coxiella burnetii is the causative agent of Q fever, for which there is yet to be an FDA-approved vaccine. This bacterial pathogen has both extra- and intracellular stages in its life cycle, and therefore both a cell-mediated (i.e., T lymphocyte) and humoral (i.e., antibody) immune response are necessary for effective eradication of this pathogen. However, most proposed vaccines elicit strong responses to only one mechanism of adaptive immunity, and some can either cause reactogenicity or lack sufficient immunogenicity. In this work, we aim to apply a nanoparticle-based platform toward producing both antibody and T cell immune responses against C. burnetii. We investigated three approaches for conjugation of the immunodominant outer membrane protein antigen (CBU1910) to the E2 nanoparticle to obtain a consistent antigen orientation: direct genetic fusion, high affinity tris-NTA-Ni conjugation to polyhistidine-tagged CBU1910, and the SpyTag/SpyCatcher (ST/SC) system. Overall, we found that the ST/SC approach yielded nanoparticles loaded with the highest number of antigens while maintaining stability, enabling formulations that could simultaneously co-deliver the protein antigen (CBU1910) and adjuvant (CpG1826) on one nanoparticle (CBU1910-CpG-E2). Using protein microarray analyses, we found that after immunization, antigen-bound nanoparticle formulations elicited significantly higher antigen-specific IgG responses than soluble CBU1910 alone and produced more balanced IgG1/IgG2c ratios. Although T cell recall assays from these protein antigen formulations did not show significant increases in antigen-specific IFN-γ production compared to soluble CBU1910 alone, nanoparticles conjugated with a CD4 peptide epitope from CBU1910 generated elevated T cell responses in mice to both the CBU1910 peptide epitope and whole CBU1910 protein. These investigations highlight the feasibility of conjugating antigens to nanoparticles for tuning and improving both humoral- and cell-mediated adaptive immunity against C. burnetii.

Unveiling promising immunogenic targets in Coxiella burnetii through in silico analysis: paving the way for novel vaccine strategies.

BACKGROUND: Coxiella burnetii, an intracellular pathogen, serves as the causative agent of zoonotic Q fever. This pathogen presents a significant threat due to its potential for airborne transmission, environmental persistence, and pathogenicity. The current whole-cell vaccine (WCV) utilized in Australia to combat Q fever exhibits notable limitations, including severe adverse reactions and limited regulatory approval for human use. This research employed the reverse vaccinology (RV) approach to uncover antigenic proteins and epitopes of C. burnetii, facilitating the development of more potent vaccine candidates. METHODS: The potential immunogenic proteins derived from C. burnetii RSA493/Nine Mile phase I (NMI) were extracted through manual, automated RV, and virulence factor database (VFDB) methods. Web tools and bioinformatics were used to evaluate physiochemical attributes, subcellular localization, antigenicity, allergenicity, human homology, B-cell epitopes, MHC I and II binding ratios, functional class scores, adhesion probabilities, protein-protein interactions, and molecular docking. RESULTS: Out of the 1850 proteins encoded by RSA493/NMI, a subset of 178 demonstrated the potential for surface or membrane localization. Following a series of analytical iterations, 14 putative immunogenic proteins emerged. This collection included nine proteins (57.1%) intricately involved in cell wall/membrane/envelope biogenesis processes (CBU_0197 (Q83EW1), CBU_0311 (Q83EK8), CBU_0489 (Q83E43), CBU_0939 (Q83D08), CBU_1190 (P39917), CBU_1829 (Q83AQ2), CBU_1412 (Q83BU0), CBU_1414 (Q83BT8), and CBU_1600 (Q83BB2)). The CBU_1627 (Q83B86 ) (7.1%) implicated in intracellular trafficking, secretion, and vesicular transport, and CBU_0092 (Q83F57) (7.1%) contributing to cell division. Additionally, three proteins (21.4%) displayed uncharacterized functions (CBU_0736 (Q83DJ4), CBU_1095 (Q83CL9), and CBU_2079 (Q83A32)). The congruent results obtained from molecular docking and immune response stimulation lend support to the inclusion of all 14 putative proteins as potential vaccine candidates. Notably, seven proteins with well-defined functions stand out among these candidates. CONCLUSIONS: The outcomes of this study introduce promising proteins and epitopes for the forthcoming formulation of subunit vaccines against Q fever, with a primary emphasis on cellular processes and the virulence factors of C. burnetii.

Current Status of Q Fever and the Challenge of Outbreak Preparedness in Korea: One Health Approach to Zoonoses.

Human Q fever, a zoonosis caused by Coxiella burnetii, presents with diverse clinical manifestations ranging from mild self-limited febrile illnesses to life-threatening complications such as endocarditis or vascular infection. Although acute Q fever is a benign illness with a low mortality rate, a large-scale outbreak of Q fever in the Netherlands led to concerns about the possibility of blood transfusion-related transmission or obstetric complications in pregnant women. Furthermore, a small minority (< 5%) of patients with asymptomatic or symptomatic infection progress to chronic Q fever. Chronic Q fever is fatal in 5-50% of patients if left untreated. In South Korea, Q fever in humans was designated as a notifiable infectious disease in 2006, and the number of Q fever cases has increased sharply since 2015. Nonetheless, it is still considered a neglected and under-recognized infectious disease. In this review, recent trends of human and animal Q fever in South Korea, and public health concerns regarding Q fever outbreaks are reviewed, and we consider how a One Health approach could be applied as a preventive measure to prepare for zoonotic Q fever outbreaks.

[In silico Design of a New Multi-Epitope Peptide-Based Vaccine Candidate Against Q Fever].

Novel types of the vaccines with high immunogenicity and low risks, including epitope-based vaccines, are sought. Among zoonotic disease, Q fever caused by Coxiella burnetii is an important target due to numerous outbreaks and the pandemic potential. Here we present a synthetic multi-epitope vaccine against Coxiella burnetii. This vaccine was developed using immunoinformatics approach. Antigenic proteins were studied, and five T cell epitopes were selected. Antigenicity, allergenicity, and toxicity of the selected epitopes were evaluated using the VaxiJen 2.0, AllerTOP, and ToxinPred servers, respectively. Selected epitopes were joined in a peptide sequence, with the cholera toxin В subunit (CTXB) as an adjuvant. The affinity of the proposed vaccine to MHCI and II molecules was measured in a molecular docking study. Resultant vaccine has high antigenicity, stability, and a half-life compatible with utilization in vaccination programs. In conclusion, the validated epitope sequences may be used as a potential vaccine to ensure protection against Q fever agent.

Q fever prevention: Perspectives from university animal science and veterinary students and livestock farmers.

OBJECTIVE: To explore animal science and veterinary students' and livestock farmers' perceptions concerning Q fever prevention. DESIGN: An online survey with an open-ended question seeking knowledge and perceptions about Q fever prevention was distributed among participants during March-September 2019. We applied thematic analysis to identify emerging themes. SETTING: Animal science and veterinary students enrolled at the University of Adelaide and members of Livestock South Australia representing cattle, sheep and goat farmers in South Australia. PARTICIPANTS: A total of56 animal science and veterinary students and 154 livestock farmers responded to the open-ended question. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Perceived challenges and opportunities for a coordinated Q fever prevention approach including human vaccination reported by the participants. RESULTS: Two major themes arose in each group. Students and farmers viewed Q fever vaccination as important. However, excessive cost for students was a barrier and for farmers, it was general practitioners' lack of knowledge of Q fever and access to an accredited immunisation provider. Similarly, both groups highlighted the need for education and increasing public and community awareness of Q fever. CONCLUSION: Our findings underscore that a sector-wide approach involving community awareness programmes, education and training for general practitioners, and subsidised vaccination as well as commitment from government and industry partners may contribute to reducing the burden of Q fever among at-risk populations.

Q Fever awareness and risk profiles among agricultural show attendees.

OBJECTIVE: To assess awareness and risk of Q fever among agricultural show attendees. SETTING: University of New England's Farm of the Future Pavilion, 2019, Sydney Royal Agricultural Show. PARTICIPANTS: Participants were ≥18 years, fluent in English, Australian residents, and gave their informed consent. MAIN OUTCOME MEASURES: Participants reported whether they had ever heard of Q fever and then completed the 'Q Tool' (www.qfevertool.com), which was used to assess participants' demographics and risk profiles. Cross-tabulations and logistic regression analyses were used to examine the relationship between these factors. RESULTS: A total of 344 participants were recruited who, in general, lived in major NSW cities and were aged 40-59 years. 62% were aware of Q fever. Living in regional/remote areas and regular contact with livestock, farms, abattoirs and/or feedlots increased the likelihood of Q fever awareness. Direct or indirect contact with feral animals was not associated with Q fever awareness after controlling for the latter risk factors. 40% of participants had a high, 21% a medium, and 30% a low risk of exposure. Slightly less than 10% reported a likely existing immunity or vaccination against Q fever. Among those who were not immune, living in a regional or remote area and Q fever awareness were independently associated with increased likelihood of exposure. CONCLUSIONS: Awareness of Q fever was relatively high. Although 61% of participants had a moderate to high risk of exposure to Q fever, they had not been vaccinated. This highlights the need to explore barriers to vaccination including accessibility of providers and associated cost.

Host cell depletion of tryptophan by IFNγ-induced Indoleamine 2,3-dioxygenase 1 (IDO1) inhibits lysosomal replication of Coxiella burnetii.

Most intracellular pathogens that reside in a vacuole prevent transit of their compartment to lysosomal organelles. Effector mechanisms induced by the pro-inflammatory cytokine Interferon-gamma (IFNγ) can promote the delivery of pathogen-occupied vacuoles to lysosomes for proteolytic degradation and are therefore important for host defense against intracellular pathogens. The bacterial pathogen Coxiella burnetii is unique in that, transport to the lysosome is essential for replication. The bacterium modulates membrane traffic to create a specialized autophagolysosomal compartment called the Coxiella-containing vacuole (CCV). Importantly, IFNγ signaling inhibits intracellular replication of C. burnetii, raising the question of which IFNγ-activated mechanisms restrict replication of a lysosome-adapted pathogen. To address this question, siRNA was used to silence a panel of IFNγ-induced genes in HeLa cells to identify genes required for restriction of C. burnetii intracellular replication. This screen demonstrated that Indoleamine 2,3-dioxygenase 1 (IDO1) contributes to IFNγ-mediated restriction of C. burnetii. IDO1 is an enzyme that catabolizes cellular tryptophan to kynurenine metabolites thereby reducing tryptophan availability in cells. Cells deficient in IDO1 function were more permissive for C. burnetii replication when treated with IFNγ, and supplementing IFNγ-treated cells with tryptophan enhanced intracellular replication. Additionally, ectopic expression of IDO1 in host cells was sufficient to restrict replication of C. burnetii in the absence of IFNγ signaling. Using differentiated THP1 macrophage-like cells it was determined that IFNγ-activation resulted in IDO1 production, and that supplementation of IFNγ-activated THP1 cells with tryptophan enhanced C. burnetii replication. Thus, this study identifies IDO1 production as a key cell-autonomous defense mechanism that limits infection by C. burnetii, which suggests that peptides derived from hydrolysis of proteins in the CCV do not provide an adequate supply of tryptophan for bacterial replication.

Cost-effectiveness of Screening Program for Chronic Q Fever, the Netherlands.

In the aftermath of a large Q fever (QF) epidemic in the Netherlands during 2007-2010, new chronic QF (CQF) patients continue to be detected. We developed a health-economic decision model to evaluate the cost-effectiveness of a 1-time screening program for CQF 7 years after the epidemic. The model was parameterized with spatial data on QF notifications for the Netherlands, prevalence data from targeted screening studies, and clinical data from the national QF database. The cost-effectiveness of screening varied substantially among subpopulations and geographic areas. Screening that focused on cardiovascular risk patients in areas with high QF incidence during the epidemic ranged from cost-saving to €31,373 per quality-adjusted life year gained, depending on the method to estimate the prevalence of CQF. The cost per quality-adjusted life year of mass screening of all older adults was €70,000 in the most optimistic scenario.

Q fever and prevention.

Coxiella burnetii is an intracellular, Gram-negative bacterium and the etiological agent of Q fever, a worldwide zoonotic disease with a considerable economic impact in the livestock industry. Domesticated ruminants like cattle, sheep, and goats are the main reservoirs of Q fever in men. Humans usually acquire the disease by inhaling contaminated aerosol produced by infected livestock. Acute infection is typically asymptomatic or manifests as a febrile flu-like illness or pneumonia. In 1-5% of primary infections, chronic Q fever may develop, which can be life-threatening and often presents as endocarditis. Q fever outbreaks usually occur from occupational exposure involving shepherds, veterinarians, animal handlers, abattoir or dairy workers, and laboratory personnel working with C. burnetii. Thus, prevention and control efforts should be primarily directed toward these groups and the surrounding environment. The most effective way of prophylaxis is vaccination. Although clinical data are lacking, vaccination should also be considered for persons who are at higher risk for development of chronic Q fever, including those with cardiac valve defects, vascular aneurysms, and immunocompromised patients. Therefore, development of an effective and harmless vaccine is a subject of constant interest of researchers for decades. This review summarizes the progress toward Q fever vaccine development.

Chemokine Receptor 7 Is Essential for Coxiella burnetii Whole-Cell Vaccine-Induced Cellular Immunity but Dispensable for Vaccine-Mediated Protective Immunity.

BACKGROUND: Protective immunity against Coxiella burnetii infection is conferred by vaccination with virulent (PI-WCV), but not avirulent (PII-WCV) whole-cell inactivated bacterium. The only well-characterized antigenic difference between virulent and avirulent C. burnetii is they have smooth and rough lipopolysaccharide (LPS), respectively. METHODS: Mice were vaccinated with PI-WCV and PII-WCV. Humoral and cellular responses were evaluated using protein chip microarrays and ELISpots, respectively. Dendritic cell (DC) maturation after stimulation with PI-WVC and PII-WVC was evaluated using flow cytometry. Vaccine-challenge studies were performed to validate the importance of the receptor CCR7. RESULTS: Other than specific antibody response to PI-LPS, similar antibody profiles were observed but IgG titers were significantly higher after vaccination with PI-WCV. Furthermore, higher frequency of antigen-specific CD4+ T cells was detected in mice immunized with PI-WCV. PI-WCV-stimulated DCs displayed significantly higher levels of CCR7 and migratory ability to secondary lymphoid organs. Challenge-protection studies in wild-type and CCR7-deficient mice confirmed that CCR7 is critical for PI-WCV-induced cellular immunity. CONCLUSIONS: PI-WVC stimulates protective immunity to C. burnetii in mice through stimulation of migratory behavior in DCs for protective cellular immunity. Additionally, the humoral immune response to LPS is an important component of protective immunity.

Eosinophils Affect Antibody Isotype Switching and May Partially Contribute to Early Vaccine-Induced Immunity against Coxiella burnetii.

Coxiella burnetii is an obligate intracellular Gram-negative bacterium which causes human Q fever. An acidified citrate cysteine medium (ACCM-2) has been developed which mimics the intracellular replicative niche of C. burnetii and allows axenic growth of the bacteria. To determine if C. burnetii cultured in ACCM-2 retains immunogenicity, we compared the protective efficacies of formalin-inactivated C. burnetii Nine Mile phase I (PIV) and phase II (PIIV) vaccines derived from axenic culture 7, 14, and 28 days postvaccination. PIV conferred significant protection against virulent C. burnetii as early as 7 days postvaccination, which suggests that ACCM-2-derived PIV retains immunogenicity and protectivity. We analyzed the cellular immune response in spleens from PIV- and PIIV-vaccinated mice by flow cytometry at 7 and 14 days postvaccination and found significantly more granulocytes in PIV-vaccinated mice than in PIIV-vaccinated mice. Interestingly, we found these infiltrating granulocytes to be SSChigh CD11b+ CD125+ Siglec-F+ (where SSChigh indicates a high side scatter phenotype) eosinophils. There was no change in the number of eosinophils in PIV-vaccinated CD4-deficient mice compared to the level in controls, which suggests that eosinophil accumulation is CD4+ T cell dependent. To evaluate the importance of eosinophils in PIV-mediated protection, we vaccinated and challenged eosinophil-deficient ΔdblGATA mice. ΔdblGATA mice had significantly worse disease than their wild-type counterparts when challenged 7 days postvaccination, while no significant difference was seen at 28 days postvaccination. Nevertheless, ΔdblGATA mice had elevated serum IgM with decreased IgG1 and IgG2a whether mice were challenged at 7 or 28 days postvaccination. These results suggest that eosinophils may play a role in early vaccine protection against C. burnetii and contribute to antibody isotype switching.

Coxiella burnetii Intratracheal Aerosol Infection Model in Mice, Guinea Pigs, and Nonhuman Primates.

Coxiella burnetii, the etiological agent of Q fever, is a Gram-negative bacterium transmitted to humans by inhalation of contaminated aerosols. Acute Q fever is often self-limiting, presenting as a febrile illness that can result in atypical pneumonia. In some cases, Q fever becomes chronic, leading to endocarditis that can be life threatening. The formalin-inactivated whole-cell vaccine (WCV) confers long-term protection but has significant side effects when administered to presensitized individuals. Designing new vaccines against C. burnetii remains a challenge and requires the use of clinically relevant modes of transmission in appropriate animal models. We have developed a safe and reproducible C. burnetii aerosol challenge in three different animal models to evaluate the effects of pulmonary acquired infection. Using a MicroSprayer aerosolizer, BL/6 mice and Hartley guinea pigs were infected intratracheally with C. burnetii Nine Mile phase I (NMI) and demonstrated susceptibility as determined by measuring bacterial growth in the lungs and subsequent dissemination to the spleen. Histological analysis of lung tissue showed significant pathology associated with disease, which was more severe in guinea pigs. Infection using large-particle aerosol (LPA) delivery was further confirmed in nonhuman primates, which developed fever and pneumonia. We also demonstrate that vaccinating mice and guinea pigs with WCV prior to LPA challenge is capable of eliciting protective immunity that significantly reduces splenomegaly and the bacterial burden in spleen and lung tissues. These data suggest that these models can have appreciable value in using the LPA delivery system to study pulmonary Q fever pathogenesis as well as designing vaccine countermeasures to C. burnetii aerosol transmission.

Coxiella burnetii Epitope-Specific T-Cell Responses in Patients with Chronic Q Fever.

Infection with Coxiella burnetii, the causative agent of Q fever, can result in life-threatening persistent infection. Reactogenicity hinders worldwide implementation of the only licensed human Q fever vaccine. We previously demonstrated long-lived immunoreactivity in individuals with past symptomatic and asymptomatic Coxiella infection (convalescents) to promiscuous HLA class II C. burnetii epitopes, providing the basis for a novel T-cell targeted subunit vaccine. In this study, we investigated in a cohort of 22 individuals treated for persistent infection (chronic Q fever) whether they recognize the same set of epitopes or distinct epitopes that could be candidates for a therapeutic vaccine or aid in the diagnosis of persistent infection. In cultured enzyme-linked immunosorbent spot (ELISpot) assays, individuals with chronic Q fever showed strong class II epitope-specific responses that were largely overlapping with the peptide repertoire identified previously for convalescents. Five additional peptides were recognized more frequently by chronic subjects, but there was no combination of epitopes uniquely recognized by or nonreactive in subjects with chronic Q fever. Consistent with more recent/prolonged exposure, we found, however, stronger ex vivo responses by direct ELISpot to both whole-cell C. burnetii and individual peptides in chronic patients than in convalescents. In conclusion, we have validated and expanded a previously published set of candidate epitopes for a novel T-cell targeted subunit Q fever vaccine in treated patients with chronic Q fever and demonstrated that they successfully mounted a T-cell response comparable to that of convalescents. Finally, we demonstrated that individuals treated for chronic Q fever mount a broader ex vivo response to class II epitopes than convalescents, which could be explored for diagnostic purposes.

Seroprevalence of Q fever among metropolitan and non-metropolitan blood donors in New South Wales and Queensland, 2014-2015.

OBJECTIVES: To estimate the prevalence of exposure to the causative agent of Q fever (Coxiella burnetii) and of current infections among blood donors in Australia. DESIGN, SETTING: Cross-sectional study in metropolitan Sydney and Brisbane, and in non-metropolitan regions with high Q fever notification rates (Hunter New England in New South Wales; Toowoomba in Queensland). PARTICIPANTS: Blood donors attending Red Cross collection centres during October 2014 - June 2015 who provided sera and completed a questionnaire on Q fever vaccination status, diagnosis and knowledge, and exposure history. MAIN OUTCOME MEASURES: Age- and sex-standardised seroprevalence of phase II IgG antibodies to C. burnetii (indicating past exposure) and independent risk factors for seropositivity; presence of C. burnetii DNA (indicating current infection and risk of transmission by blood transfusion). RESULTS: 2740 donors (94.5% response rate) completed the questionnaire and supplied sera for analysis. Crude antibody seroprevalence was 3.6%. Standardised seroprevalence was higher in non-metropolitan than metropolitan regions (NSW, 3.7% v 2.8%; Queensland, 4.9% v 1.6%; statistically significant only in Queensland). Independent predictors of antibody seropositivity were regular contact with sheep, cattle, or goats (adjusted odds ratio [aOR], 5.3; 95% CI, 2.1-14), abattoir work (aOR, 2.2; 95% CI, 1.2-3.9), and assisting at an animal birth (aOR, 2.1; 95% CI, 1.2-3.6). Having lived in a rural area but having only rare or no contact with sheep, cattle or goats was itself a significant risk factor (v never lived rurally: aOR, 2.5; 95% CI, 1.1-5.9). 40% of people in groups recommended for vaccination were aware of the vaccine; 10% of people in these groups had been vaccinated. C. burnetii DNA was not detected in 1681 non-metropolitan samples, suggesting that transmission by blood donation is unlikely. CONCLUSIONS: Given their exposure to multiple risk factors, vaccination against Q fever should be considered for all rural residents.

Q fever vaccination of children in Australia: Limited experience to date.

AIM: Q fever is a zoonotic disease caused by the bacterium Coxiella burnetii and is associated with significant morbidity and mortality in both adults and children. Australia is the only country that has produced and registered a Q fever vaccine for human use, but this vaccine is licenced only for people aged over 15 years as data and experience in children are limited. This review describes the experience of Q fever vaccination of known paediatric cases in Australia to date. METHODS: Patients aged younger than 15 years who received the Q fever vaccination had data abstracted from medical records after consent was obtained from the relevant guardians. Data on risk factors for Q fever, skin testing procedure, dose of vaccination, adverse effects and follow-up assessment were obtained. RESULTS: Twelve children were identified as having received the Q fever vaccination. Vaccination was feasible, with empirical weight-based dose adjustment performed for younger children. There were no significant adverse effects. CONCLUSIONS: Q fever vaccine may be safe in children and should be considered in children who are at significant risk of Q fever infection. Safe vaccine protocols with proven efficacy will allow children of all ages to be protected. Prospective studies of vaccination in children are indicated. Expanding available Q fever registries to include children would allow outcomes to be systematically followed.

A longitudinal study of serological responses to Coxiella burnetii and shedding at kidding among intensively-managed goats supports early use of vaccines.

Vaccination against Coxiella burnetii, the cause of Q fever, is reportedly the only feasible strategy of eradicating infection in ruminant herds. Preventive vaccination of seronegative goats is more effective in reducing shedding of C. burnetii than vaccinating seropositive goats. The age at which goats born on heavily-contaminated farms first seroconvert to C. burnetii has not yet been documented. In a 16-month birth cohort study, the age at which goats seroconverted against C. burnetii was investigated; 95 goats were bled every 2 weeks and tested for antibodies against C. burnetii. Risk factors for seroconversion were explored and goats shedding C. burnetii were identified by testing vaginal swabs taken at the goats' first kidding using a com1 polymerase chain reaction assay. The first surge in the number of goats with IgM to C. burnetii was observed at week 9. Thus, a first vaccination not later than 8 weeks of age to control C. burnetii in highly contaminated environments is indicated. The odds of seroconversion were 2.0 times higher [95% confidence interval (CI) 1.2, 3.5] in kids born by does with serological evidence of recent infection (IgM seropositive) compared to kids born by IgM seronegative does, suggesting either in utero transmission or peri-parturient infection. The rate of seroconversion was 4.5 times higher (95% CI 2.1, 9.8) during than outside the kidding season, highlighting the risk posed by C. burnetii shed during kidding, even to goats outside the kidding herd. Shedding of C. burnetii at kidding was detected in 15 out of 41 goats infected before breeding.

Effectiveness of a Mobile Short-Message-Service-Based Disease Outbreak Alert System in Kenya.

We conducted a randomized, controlled trial to test the effectiveness of a text-messaging system used for notification of disease outbreaks in Kenya. Health facilities that used the system had more timely notifications than those that did not (19.2% vs. 2.6%), indicating that technology can enhance disease surveillance in resource-limited settings.

One Health approach to controlling a Q fever outbreak on an Australian goat farm.

A recent outbreak of Q fever was linked to an intensive goat and sheep dairy farm in Victoria, Australia, 2012-2014. Seventeen employees and one family member were confirmed with Q fever over a 28-month period, including two culture-positive cases. The outbreak investigation and management involved a One Health approach with representation from human, animal, environmental and public health. Seroprevalence in non-pregnant milking goats was 15% [95% confidence interval (CI) 7-27]; active infection was confirmed by positive quantitative PCR on several animal specimens. Genotyping of Coxiella burnetii DNA obtained from goat and human specimens was identical by two typing methods. A number of farming practices probably contributed to the outbreak, with similar precipitating factors to the Netherlands outbreak, 2007-2012. Compared to workers in a high-efficiency particulate arrestance (HEPA) filtered factory, administrative staff in an unfiltered adjoining office and those regularly handling goats and kids had 5·49 (95% CI 1·29-23·4) and 5·65 (95% CI 1·09-29·3) times the risk of infection, respectively; suggesting factory workers were protected from windborne spread of organisms. Reduction in the incidence of human cases was achieved through an intensive human vaccination programme plus environmental and biosecurity interventions. Subsequent non-occupational acquisition of Q fever in the spouse of an employee, indicates that infection remains endemic in the goat herd, and remains a challenge to manage without source control.