Search Results (41)

Background/Objectives: Q-VAX vaccine, approved in Australia, prevents Q fever. However, individuals with prior Coxiella burnetii (Cb) infection have an increased risk of adverse reactions, requiring pre-vaccination screening by an intradermal hypersensitivity skin test for cell-mediated immune memory and a serological assay for anti-Cb antibodies. The week-long interval for skin test assessment limits efficient vaccination. This study evaluated a standardized interferon-γ release assay (IGRA) as a potential skin test alternative. Methods: Immune assays were compared in Australian populations with different incidences of prior Cb exposure. Cell-mediated immunity was assessed by the Q-VAX skin test and IGRA. Serological status was evaluated with established diagnostic assays. Hypothetical vaccine eligibility decisions using combined IGRA and serology results were compared with actual clinical decisions made using current guidelines. Results: All tests performed better in detecting prior infection than in detecting prior vaccination. Only the IGRA identified all individuals with a known history of Q fever. Agreement between the skin test and IGRA was limited. Moderate agreement was observed between hypothetical vaccine eligibility determinations based on IGRA plus serology results and actual clinical decisions. IGRA-positive but serology- and skin test-negative individuals received Q-VAX without clinically significant side effects, suggesting that elevated IGRA responses alone are not predictive of susceptibility to vaccine reactogenicity. Conclusions: The IGRA is not yet a suitable skin test replacement when assessing eligibility for Q fever vaccination, despite the significant limitations of the latter. We offer recommendations for designing future studies that might allow the development of appropriate guidelines for IGRA use in vaccine eligibility screening. Full article

Several indirect findings suggest that host-related factors influence susceptibility to Coxiella burnetii infection. We decided to explore the influence of genetic factors related to both innate and adaptive immunity in acute Q fever susceptibility. TLR2 (Arg753Gln) and TLR4 (Asp299Gly, Thr399Ile) polymorphisms, along with HLA-DRB1 alleles, were analyzed for 38 patients with acute Q fever, 38 matched controls, and 121 blood donors. No significant associations were found for TLR polymorphisms. However, HLA-DRB1*04 was more frequent in patients. HLA-DRB1 variants may play a role in Q fever susceptibility, supporting the need for further investigation into their potential implications for vaccination and risk assessment. Full article

Background: The fatality rate of hemorrhagic fever with renal syndrome (HFRS), due to hantavirus transmitted by rodents, ranges from 1% to 12%. This study aims to delineate the clinical and laboratory characteristics of HFRS, identify factors associated with disease severity, and construct and validate a nomogram for prognosis prediction of HFRS in the central part of China. Methods: Out of 598 HFRS patients diagnosed via serology tests from four hospitals in Hubei Province, 551 were included. Clinical data were gathered and analyzed, followed by logistic univariate and multivariate analyses to identify independent prognostic factors. A nomogram was developed and validated to forecast the patient’s prognosis. Results: Vaccination led to a notable drop in HFRS incidence from 2018 to 2019, and seasonal trends exhibited bimodal changes with peaks from May to July and November to January. The 30-day mortality rate was 4.17% (23/551). Red blood cell count (RBC), age, two-stage overlap, qSOFA ≥ 2, aspartate aminotransferase (AST), and three-stage overlap were identified as independent prognostic factors. A predictive risk classification system using a nomogram chart was developed, and Kaplan–Meier curves indicated that the new system accurately distinguished 30-day mortality among the three risk groups. Conclusions: The risk score (EASTAR) system demonstrated good predictive performance for prognostic prediction, and it can be applied to quickly screen patients who require ICU admission. Full article

Q fever is a zoonotic disease caused by the obligate intracellular bacterium Coxiella burnetii that presents significant challenges for global public health control. Current prevention relies primarily on the whole-cell vaccine “Q-VAX”, which despite its effectiveness, faces important limitations including pre-screening requirements and reactogenicity issues in previously sensitized individuals. This comprehensive review examines the complex interplay between pathogen characteristics, host immune responses, and vaccine development strategies. We analyze recent advances in understanding C. burnetii’s molecular pathogenesis and host–pathogen interactions that have informed vaccine design. The evolution of vaccine approaches is evaluated, from traditional whole-cell preparations to modern subunit, DNA, and multi-epitope designs. Particular attention is given to innovative technologies, including reverse vaccinology and immunoinformatics, that have enabled the identification of novel antigenic targets. Recent clinical data demonstrating the safety and immunogenicity of next-generation vaccine candidates are presented, alongside manufacturing and implementation considerations. While significant progress has been made in overcoming the limitations of first-generation vaccines, challenges remain in optimizing immunogenicity while ensuring safety across diverse populations. This review provides a critical analysis of current evidence and future directions in Q fever vaccine development, highlighting promising strategies for achieving more effective and broadly applicable vaccines. Full article

The African swine fever virus (ASFV) causes severe disease in wild and domestic pigs, with high mortality rates, extensive spread, and significant economic losses globally. Despite ongoing efforts, an effective vaccine remains elusive. Therefore, effective diagnostic methods are needed to rapidly detect and prevent the further spread of ASF. This study assessed nine commercial kits based on real-time polymerase chain reaction (PCR) approved in the Republic of Korea using the synthesized ASFV plasmid, 20 food waste samples, and artificially spiked samples (ASSs). The kits were evaluated for their diagnostic sensitivity, specificity, cost per reaction, and reaction running time. In addition, the results were compared with those of the World Organization for Animal Health (WOAH) standard methods. Three commercial kits (VDx^® ASFV qPCR Kit, Palm PCR™ ASFV Fast PCR Kit, and PowerChek™ ASFV Real-time PCR Detection Kit Ver.1.0) demonstrated the highest sensitivity (100 ag/μL), cost-effectiveness (less than KRW 10,000), and shortest running time (less than 70 min). These kits are suitable for the monitoring, early diagnosis, and prevention of the spread of ASF. This is the first report on the performance comparison of ASFV diagnostic kits approved in the Republic of Korea, providing valuable information for selecting kits for testing with food waste samples. Full article

Q fever is a zoonosis caused by Coxiella burnetii, primarily affecting those in close contact with domestic ruminants, the main source of human infection. Coxiella burnetii has also been detected in various wildlife species globally. In Australia, serological and molecular studies have shown exposure to and infection by C. burnetii in macropods, bandicoots, and koalas. However, the extent to which these species contribute to human infection remains unclear. An unpublished public health investigation into a Q fever case in a person involved in koala care could not conclusively link the infection to koalas due to the patient’s broad animal exposure. This study aimed to explore the potential role of koalas in transmitting C. burnetii to humans by investigating the presence of C. burnetii DNA in urogenital tract (UGT) swabs from koalas. DNA was extracted from UGT swabs from koalas in three regions in New South Wales, Australia. An optimised multiplex qPCR assay detected C. burnetii DNA in 2 out of 225 samples (0.89%) at approximately 10 genome equivalents per reaction. Both positive samples amplified all three gene targets. MLVA genotyping identified two distinct C. burnetii genotypes previously isolated from Australian Q fever cases. These findings highlight the need for vaccination against Q fever for those in close contact with koalas. Full article

African swine fever (ASF), caused by the African swine fever virus (ASFV), has resulted in significant losses in the global pig industry. Considering the absence of effective vaccines, developing drugs against ASFV may be a crucial strategy for its prevention and control in the future. In this study, punicalagin, a polyphenolic substance extracted from pomegranate peel, was found to significantly inhibit ASFV replication in MA-104, PK-15, WSL, and 3D4/21 cells by screening an antiviral compound library containing 536 compounds. Time-of-addition studies demonstrated that punicalagin acted on early viral replication stages, impinging on viral attachment and internalization. Meanwhile, punicalagin could directly inactivate the virus according to virucidal assay. RT-qPCR and Western blot results indicated that punicalagin modulated the NF-κB/STAT3/NLRP3 inflammasome signaling pathway and reduced the levels of inflammatory mediators induced by ASFV. In conclusion, this study reveals the anti-ASFV activity of punicalagin and the mechanism of action, which may have great potential for developing effective drugs against ASFV. Full article

African swine fever (ASF) has become a global pandemic due to inadequate prevention and control measures, posing a significant threat to the swine industry. Despite the approval of a single vaccine in Vietnam, no antiviral drugs against the ASF virus (ASFV) are currently available. Aloperine (ALO), a quinolizidine alkaloid extracted from the seeds and leaves of bitter beans, exhibits various biological functions, including anti-inflammatory, anti-cancer, and antiviral activities. In this study, we found that ALO could inhibit ASFV replication in MA-104, PK-15, 3D4/21, and WSL cells in a dose-dependent manner without cytotoxicity at 100 μM. Furthermore, it was verified that ALO acted on the co- and post-infection stages of ASFV by time-of-addition assay, and inhibited viral internalization rather than directly inactivating the virus. Notably, RT-qPCR analysis indicated that ALO did not exert anti-inflammatory activity during ASFV infection. Additionally, gene ontology (GO) and KEGG pathway enrichment analyses of transcriptomic data revealed that ALO could inhibit ASFV replication via the PRLR/JAK2 signaling pathway. Together, these findings suggest that ALO effectively inhibits ASFV replication in vitro and provides a potential new target for developing anti-ASFV drugs. Full article

The African swine fever virus (ASFV) is an ancient, structurally complex, double-stranded DNA virus that causes African swine fever. Since its discovery in Kenya and Africa in 1921, no effective vaccine or antiviral strategy has been developed. Therefore, the selection of more suitable vaccines or antiviral targets is the top priority to solve the African swine fever virus problem. B125R, one of the virulence genes of ASFV, encodes a non-structural protein (pB125R), which is important in ASFV infection. However, the epitope of pB125R is not well characterized at present. We observed that pB125R is specifically recognized by inactivated ASFV-positive sera, suggesting that it has the potential to act as a protective antigen against ASFV infection. Elucidation of the antigenic epitope within pB125R could facilitate the development of an epitope-based vaccine targeting ASFV. In this study, two strains of monoclonal antibodies (mAbs) against pB125R were produced by using the B cell hybridoma technique, named 9G11 and 15A9. The antigenic epitope recognized by mAb 9G11 was precisely located by using a series of truncated ASFV pB125R. The ⁵²DPLASQRDIYY⁶² (epitope on ASFV pB125R) was the smallest epitope recognized by mAb 9G11 and this epitope was highly conserved among different strains. The key amino acid sites were identified as D52, Q57, R58, and Y62 by the single-point mutation of 11 amino acids of the epitope by alanine scanning. In addition, the immunological effects of the epitope (pB125R-DY) against 9G11 were evaluated in mice, and the results showed that both full-length pB125R and the epitope pB125R-DY could induce effective humoral and cellular immune responses in mice. The mAbs obtained in this study reacted with the eukaryotic-expressed antigen proteins and the PAM cell samples infected with ASFV, indicating that the mAb can be used as a good tool for the detection of ASFV antigen infection. The B cell epitopes identified in this study provide a fundamental basis for the research and development of epitope-based vaccines against ASFV. Full article

Coxiella burnetii is the causative agent of Q fever. The main reservoirs for this bacterium, which can lead to human infection, in our region are typically cattle, goats, and sheep. In animals, C. burnetii infection is often detected due to reproductive problems. European Member States are required to report confirmed cases annually, but the lack of uniform reporting methods makes the data rather inconsistent. The Istituto Zooprofilattico Sperimentale dell’Abruzzo e del Molise is involved in official controls to identify the causes of abortions, monitor suspected or positive herds, evaluate suspected infections in pets and humans, monitor the spread in wildlife, etc. In this paper, we summarize the presence of C. burnetii over the last five years (2019–2023). Additionally, a detailed overview of C. burnetii infection in wild and domestic animals is provided. Five hundred sixty animals—including cattle; goats; sheep; wild animals, such as deer, boars, wolves, roe deer, owls, and otters; buffalo; dogs; horses; cats; and a donkey—and six human samples were tested by real-time PCR on the transposase gene IS1111 to detect C. burnetii. The MST profile was identified in some of the samples. Outbreaks of C. burnetii occurred in four herds. In one of them, it was possible to follow the outbreak from inception to eradication by evaluating the effect of vaccination on real-time PCR Ct values. A total of 116 animals tested positive for C. burnetii, including 73 goats, 42 sheep, and one bovine. None of the other samples tested positive. The strains for which the ST was performed were identified as ST79, a strain that has been present in the area for more than ten years. The effect of vaccination on the reduction of positive samples and the variation of real-time PCR Ct values was evaluated in strict correlation. Full article

To establish a rapid real-time RT-PCR method for differentiating wild-type classical swine fever virus (CSFV) strains from vaccine strains (HCLV), we designed a universal primer targeting the NS3 gene to detect wild-type CSFV strains and vaccine strains simultaneously, and two TaqMan-MGB probes were designed to differentiate between wild-type and vaccine strains. After optimizing the RT-qPCR conditions, a rapid dual TaqMan-MGB RT-qPCR method for the detection and identification of CSFV and HCLV was developed. The results showed that method could specifically detect CSFV and HCLV with no cross-reactivity with other swine pathogens. The analytic sensitivity for the NS3 gene of CSFV and HCLV were 1.67 × 10¹ copies/μL, respectively. For precision testing, the repeatability and reproducibility of the test was less than 2%. This method was successfully used for the rapid detection of 193 biological samples collected from CSFV-vaccinated pigs. This fast and accurate detection technology can be used for the detection of CSFV and is suitable for differentiating between wild-type CSFV strains and vaccine strains. Full article

Q fever is a disease caused by Coxiella burnetii that affects many animal species and humans. In ruminants, the disease is responsible for several reproductive disorders (such as abortions, stillbirths, premature births, weak offspring, retained foetal membranes and infertility). An inactivated vaccine based on a phase I antigen of C. burnetii is available for cattle, goats and sheep. This review aims to summarise the scientific literature regarding the efficacy and safety of this vaccine to control the infection in these three domestic ruminant species. Forty-five publications and one experimental veterinary thesis reporting on experimental studies, case reports, mathematical modelling and intervention studies were selected according to the PRISMA guidelines. Although some studies lack control groups or statistical analyses, for all three species, published data show that vaccination often results in a reduction in abortions and an improvement in reproductive performance in comparison with absence of vaccination. There is also evidence, including in infected herds and animals, that vaccination is associated with a reduction in bacterial shedding, both in intensity and duration in comparison with absence of vaccination. For these reasons, in case of human outbreaks, vaccination is one of the pillars of control measures. Vaccination is generally well tolerated, despite the rare occurrence of mild, transient side-effects, such as hyperthermia and reduction in milk yield. Full article

It was the aim of this study to examine whether the usage of the vaccine COXEVAC^® (Ceva Santé Animale) could reduce the consumption of antibiotics in Q-fever-positive dairy farms. Additionally, the effects of other herd-level factors on the consumption of antibiotics were investigated. A total of 36 farms with vaccination and 13 farms without vaccination participated in this longitudinal cohort study. In all herds, Coxiella burnetii had been directly or indirectly diagnosed. To compare the treatment frequency of antibiotics between the vaccinated group and the non-vaccinated group, the consumption of antibiotics for each farm was collected using the veterinary documents about the application and delivery of antibiotics. To gather detailed information about herd data, nutrition, milking management, housing, and animal health, the farmers were interviewed with the help of a questionnaire. The results thereof suggest that there might be an association between the vaccination against Q fever and a reduced consumption of antibiotics. Neither herd size nor milk yield level influenced the consumption of antibiotics in the study herds. Type of flooring and udder-cluster disinfection while milking were associated with a lower and higher therapy frequency, respectively. Further studies are necessary to elucidate the cause–effect relationship between vaccination and the consumption of antibiotics. Full article

To support farmers in their decisions related to Q fever, a dedicated economic assessment tool is developed. The present work describes the calculator, its economic rationale, and the supporting assumptions. The calculator integrates a yearly compartmental model to represent population dynamism and the main interactions between disorders linked to Q fever, especially reproductive disorders (abortion, retained foetal membranes, purulent vaginal discharge and endometritis, extra services, and calving–conception delays). The effects of the nontangible cost of the disease on human health, the welfare of the animals, and the workload of farmers were not integrated into the model. The model shows high-level sensitivity to the prevalence of Q fever in the herd prevaccination and to the costs of abortion and extra days of calving–conception intervals. Breakeven points, i.e., cost values that allow us to achieve positive vaccination benefits, are also reported. For herds with moderate or high prevalence rates of Q fever prevaccination (>30%), a vaccination benefit is observed. The vaccine should be considered a type of insurance in herds with low prevalence rates of Q fever prevaccination (≤20%). The calculator was developed to aid decision-making at the farm level, and no conclusion can be extrapolated as a generic trend based on the present work. Full article

Coxiella (C.) burnetii, a zoonotic bacterium, is prevalent in dairy farms. Some cows develop a persistent infection and shed C. burnetii into milk and occasionally by amniotic fluid at calving. Serological diagnosis of Q fever in humans is performed by phase (Ph)-specific antibody tests; PhII antibodies usually indicate an acute infection, while the development of a chronic infection is characterised by elevated PhI antibody titres. Phase-specific tests have now been established for diagnosis of coxiellosis in cattle. Additionally, an interferon-γ (IFN-γ) recall assay has been implemented to assess cellular immunity to C. burnetii in cattle. Milk samples from all lactating cows (n = 2718) of 49 Bavarian dairy farms were collected through a convenience sample and analysed for phase-specific antibodies. Antibody profiles were evaluated by age. Based on the seropositivity of first-lactation cows, three distinct herd profiles were observed: an ‘acute’ state of herd infection was characterised by a PhI⁻/PhII⁺ pattern. The detection of PhI antibodies (PhI⁺/PhII⁺) characterised the ‘chronic’ state, and seronegative results defined the ‘silent’ state of herd infection. If antibodies had not been detected in multiparous cows, the herd was considered as probably free of coxiellosis. The analysed cattle herds were noted to have an ‘acute’ (n = 12, 24.5%), ‘chronic’ (n = 18, 36.8%), or ‘silent’ state of herd infection (n = 16, 32.6%). Only three farms (6.1%) were classified as ‘free’ of C. burnetii. The detection of these herd states over a time period of 4 years in one farm indicated that the described states occur in a cyclical manner. Frequently, a wave-like profile was seen, i.e., a circumscribed seronegative age group was flanked by seropositive age groups. In seronegative animals, IFN-γ reactivity was demonstrated. Seroconversion after vaccination was observed by day 7 post-vaccination in chronically infected herds, whereas in the case of silent infection, it started by day 14. These data indicated a pre-existing immunity in seronegative animals in chronically infected herds. Additionally, IFN-γ reactivity was detected in seronegative calves (>3 months) and heifers from chronically infected farms compared to a negative farm. An infection prior to 3 months of age resulted in cellular immunity in the absence of detectable antibodies. An infection around calving would explain this. The aforementioned circumscribed seronegative age groups are, therefore, explained by an infection early in life during active shedding at calving. Based on these results, an endemic cycle of coxiellosis is proposed: Susceptible young heifers get infected by persistently infected cows. Subsequently, shedding of C. burnetii at calving results in infection and then in cellular immunity in offspring. When these calves enter the cow herd two years later, a maximum of herd immunity is achieved, shedding ceases, and new susceptible animals are raised. In an acutely infected dairy farm, the PhI⁺/PhII⁺ serological pattern prevailed in second-lactation cows. In this study, stored sera collected since birth were analysed retrospectively. From the earliest seroconversion, the peak of seroconversion took about 33 months. These data suggested a slow spread of infection within herds. The classification of dairy cow herds is a promising basis for further analysis of the clinical impact of coxiellosis. Full article