scholarly journals Com1 as a Promising Protein for the Differential Diagnosis of the Two Forms of Q Fever

Pathogens ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 242 ◽  
Author(s):  
Vranakis ◽  
Mathioudaki ◽  
Kokkini ◽  
Psaroulaki
Keyword(s):  
Differential Diagnosis ◽  
Phase I ◽  
Clinical Diagnosis ◽  
Q Fever ◽  
Control Group ◽  
Virulence Potential ◽  
Chronic Q Fever ◽  
Candidate Protein ◽  
Immunogenic Proteins ◽  
Human Infections

Coxiella burnetii is the causative agent of acute and chronic Q fever in humans. Although the isolates studied so far showed a difference in virulence potential between those causing the two forms of the disease, implying a difference in their proteomic profile, the methods used so far to diagnose the two forms of the disease do not provide sufficient discriminatory capability, and human infections may be often misdiagnosed. The aim of the current study was to identify the outer membrane Com1 (CBU_1910) as a candidate protein for serodiagnostics of Q fever. The protein was cloned, expressed, purified, and used as an antigen in ELISA. The protein was then used for the screening of sera from patients suffering from chronic Q fever endocarditis, patients whose samples were negative for phase I immunoglobulin G (IgG), patients for whom at least one sample was positive for phase I IgG, and patients suffering from any kind of rheumatoid disease. Blood donors were used as the control group. Following statistical analysis, 92.4% (122/132) of the samples tested agreed with the negative clinical diagnosis, and 72.2% (26/36) agreed with the positive clinical diagnosis. Moreover, a significant correlation to the presence of the disease (p = 0.00) was calculated. The results support the idea that a Com1 antigen-based serodiagnostic test may be useful for differential diagnosis of chronic Q fever. Further studies are required to compare more immunogenic proteins of the bacterium against samples originating from patients suffering from different forms of the disease.

scholarly journals Questing one Brazilian query: reporting 16 cases of Q fever from Minas Gerais, Brazil

2006 ◽  
Vol 48 (1) ◽  
pp. 5-9 ◽  
Author(s):  
Paulo Sérgio Gonçalves da Costa ◽  
Marco Emilio Brigatte ◽  
Dirceu Bartolomeu Greco
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Fever Of Unknown Origin ◽  
Q Fever ◽  
Acute Infection ◽  
Case Series ◽  
Febrile Illness ◽  
Unknown Origin ◽  
Clinical Form ◽  
Chronic Q Fever

Q fever has been considered non-existing in Brazil where reports of clinical cases still cannot be found. This case-series of 16 patients is a result of a systematic search for such illness by means of clinical and serologic criteria. Serologic testing was performed by the indirect microimmunofluorescence technique using phase I/II C. burnetii antigens. Influenza-like syndrome was the most frequent clinical form (eight cases - 50%), followed by pneumonia, FUO (fever of unknown origin), mono-like syndrome (two cases - 12.5% each), lymphadenitis (one case - 6.3%) and spondylodiscitis associated with osteomyelitis (one case - 6.3%). The ages varied from four to 67 years old with a median of 43.5. All but one patient had positive serologic tests for phase II IgG whether or not associated with IgM positivity compatible with acute infection. One patient had both phase I and phase II IgG antibodies compatible with chronic Q fever. Seroconvertion was detected in 10 patients. Despite the known limitations of serologic diagnosis, the cases here reported should encourage Brazilian doctors to include Q fever as an indigenous cause of febrile illness.

scholarly journals Correlation between Ratio of Serum Doxycycline Concentration to MIC and Rapid Decline of Antibody Levels during Treatment of Q Fever Endocarditis

2005 ◽  
Vol 49 (7) ◽  
pp. 2673-2676 ◽  
Author(s):  
Jean-Marc Rolain ◽  
Areen Boulos ◽  
Marie-Noëlle Mallet ◽  
Didier Raoult
Keyword(s):  
Phase I ◽  
Q Fever ◽  
Serum Levels ◽  
Response To Treatment ◽  
Rapid Decline ◽  
Shell Vial ◽  
Real Time Quantitative Pcr ◽  
Chronic Q Fever ◽  
Antibody Levels ◽  
Quantitative Pcr Assay

ABSTRACT Endocarditis is the major clinical manifestation of chronic Q fever. Although doxycycline along with hydroxychloroquine remains the mainstay of medical therapy for Q fever endocarditis, there are wide variations in the rapidity of the patient's decline of antibody levels during such therapy. We undertook a retrospective examination of whether there was any correlation between the ratio of serum concentration to MIC of doxycycline and response to treatment in patients with Q fever endocarditis. Included herein are 16 patients from whom Coxiella burnetii was isolated from cardiac valve materials. Serology and measurement of doxycycline and hydroxychloroquine serum levels were performed and recorded after 1 year of treatment. The MIC of doxycycline for C. burnetii isolates was determined using the shell vial assay in a real-time quantitative PCR assay. At the completion of a yearlong therapy with doxycycline-hydroxychloroquine, all those that showed a low decline of antibody levels (n = 6) (i.e., <2-fold decrease in antibody titer to phase I C. burnetii antigen) had a ratio of serum doxycycline concentration to MIC between 0.5 and 1. In contrast, those having a ratio of ≥1 showed a rapid decline of phase I antibody levels (n = 9; P < 0.05). The only patient who died had a serum doxycycline-to-MIC ratio of <0.5, and the isolate of C. burnetii cultured from this patient was resistant to doxycycline (MIC = 8 μg/ml). The ratio of serum doxycycline concentration to MIC should be monitored during the course of therapy in patients with Q fever endocarditis.

scholarly journals Animals withCoxiella burnetiiInfection Demonstrate a Western Immunoblot Profile of Chronic Q Fever in Humans

1996 ◽  
Vol 7 (1) ◽  
pp. 45-48
Author(s):  
TJ Marrie ◽  
Linda Yates
Keyword(s):  
Immune Response ◽  
Phase I ◽  
Phase Ii ◽  
Coxiella Burnetii ◽  
Q Fever ◽  
Western Immunoblotting ◽  
Western Immunoblot ◽  
Chronic Q Fever

Western immunoblotting was used to compare the immune response toCoxiella burnetiiphase I and phase II antigens of humans with acute and chronic Q fever with that of infected cats, rabbits, cows and raccoons. The cats, rabbits, cows and raccoons had an immunoblot profile similar to that of the human with chronic Q fever.

scholarly journals Microbiological Challenges in the Diagnosis of Chronic Q Fever

2012 ◽  
Vol 19 (5) ◽  
pp. 787-790 ◽  
Author(s):  
Linda M. Kampschreur ◽  
Jan Jelrik Oosterheert ◽  
Annemarie M. C. Koop ◽  
Marjolijn C. A. Wegdam-Blans ◽  
Corine E. Delsing ◽  
...  
Keyword(s):  
Phase I ◽  
Q Fever ◽  
Strong Association ◽  
False Negative ◽  
High Morbidity ◽  
Igg Antibody ◽  
Predictive Values ◽  
Content Type ◽  
Chronic Q Fever ◽  
High Phase

ABSTRACTDiagnosis of chronic Q fever is difficult. PCR and culture lack sensitivity; hence, diagnosis relies mainly on serologic tests using an immunofluorescence assay (IFA). Optimal phase I IgG cutoff titers are debated but are estimated to be between 1:800 and 1:1,600. In patients with proven, probable, or possible chronic Q fever, we studied phase I IgG antibody titers at the time of positive blood PCR, at diagnosis, and at peak levels during chronic Q fever. We evaluated 200 patients, of whom 93 (46.5%) had proven, 51 (25.5%) had probable, and 56 (28.0%) had possible chronic Q fever. Sixty-five percent of proven cases had positiveCoxiella burnetiiPCR results for blood, which was associated with high phase I IgG. Median phase I IgG titers at diagnosis and peak titers in patients with proven chronic Q fever were significantly higher than those for patients with probable and possible chronic Q fever. The positive predictive values for proven chronic Q fever, compared to possible chronic Q fever, at titers 1:1,024, 1:2,048, 1:4,096, and ≥1:8,192 were 62.2%, 66.7%, 76.5%, and ≥86.2%, respectively. However, sensitivity dropped to <60% when cutoff titers of ≥1:8,192 were used. Although our study demonstrated a strong association between high phase I IgG titers and proven chronic Q fever, increasing the current diagnostic phase I IgG cutoff to >1:1,024 is not recommended due to increased false-negative findings (sensitivity < 60%) and the high morbidity and mortality of untreated chronic Q fever. Our study emphasizes that serologic results are not diagnostic on their own but should always be interpreted in combination with clinical parameters.

scholarly journals Predominant Immunoglobulin A Response to Phase II Antigen of Coxiella burnetii in Acute Q Fever

1999 ◽  
Vol 6 (2) ◽  
pp. 173-177 ◽  
Author(s):  
Pierre-Edouard Fournier ◽  
Didier Raoult
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Rural Areas ◽  
Q Fever ◽  
Immunoglobulin A ◽  
Immunoglobulin M ◽  
Retrospective Case ◽  
Chronic Q Fever ◽  
Antibody Titers ◽  
Acute Q Fever

ABSTRACT Diagnosis of acute Q fever is usually confirmed by serology, on the basis of anti-phase II antigen immunoglobulin M (IgM) titers of ≥1:50 and IgG titers of ≥1:200. Phase I antibodies, especially IgG and IgA, are predominant in chronic forms of the disease. However, between January 1982 and June 1998, we observed anti-phase II antigen IgA titers of ≥1:200 as the sole or main antibody response in 10 of 1,034 (0.96%) patients with acute Q fever for whom information was available. In order to determine whether specific epidemiological or clinical factors were associated with these serological profiles, we conducted a retrospective case-control study that included completion of a standardized questionnaire, which was given to 40 matched controls who also suffered from acute Q fever. The mean age of patients with elevated phase II IgA titers was significantly higher than that usually observed for patients with acute Q fever (P = 0.026); the patients were also more likely than controls to live in rural areas (P = 0.026) and to have increased levels of transaminase in blood (P = 0.03). Elevated IgA titers are usually associated with chronic Q fever and are directed mainly at phase I antigens. Although the significance of our findings is unexplained, we herein emphasize the fact that IgA antibodies are not specific for chronic forms of Q fever and that they may occasionally be observed in patients with acute disease. Moreover, as such antibody profiles may not be determined by most laboratories, which test only for total antibody titers to phase I and II antigens, the three isotype-specific Ig titers should be determined as the first step in diagnosing Q fever.

The immune response in a cat-related outbreak of Q fever as measured by the indirect immunofluorescence test and the enzyme-linked immunosorbent assay

1990 ◽  
Vol 36 (4) ◽  
pp. 292-296 ◽  
Author(s):  
J. Embil ◽  
J. C. Williams ◽  
T. J. Marrie
Keyword(s):  
Immune Response ◽  
Phase I ◽  
Phase Ii ◽  
Q Fever ◽  
Elisa Test ◽  
Enzyme Linked Immunosorbent Assay ◽  
Whole Cells ◽  
Chronic Q Fever ◽  
Acute Q Fever ◽  
Indirect Immunofluorescent

The isotypic immune response of 16 individuals who developed Q fever pneumonia following exposure to an infected parturient cat was studied. The enzyme-linked immunosorbent (ELISA) test was used to detect IgM, IgA, and IgG antibodies to phase I and phase II Coxiella burnetii whole-cell antigens and to the phase I lipopolysaccharide. The indirect immunofluorescent antibody (IFA) test was also used to detect antibodies to phase I and phase II whole cells. None of the 16 subjects developed antibodies to the phase I lipopoly saccharide. The ELISA was more sensitive than the IFA test. IgM antibodies to phase II antigen were detectable by ELISA in 80% of the subjects at the time of onset of symptoms and were still present in 7 of the 8 tested at 32 weeks following the onset of symptoms. In all instances (ELISA: IgG, IgM; IFA: IgG, IgM) phase II antibodies developed earlier and reached higher levels than did phase I antibodies. The absence of antibodies to phase I lipopolysaccharide in acute Q fever combined with our unpublished findings of antibodies to phase I lipopoly saccharide in chronic Q fever suggests that this test may be used to distinguish acute from chronic Q fever. Key words: Q fever, immune response, ELISA.

scholarly journals Prevalence of Chronic Q Fever in Patients with a History of Cardiac Valve Surgery in an Area Where Coxiella burnetii Is Epidemic

2012 ◽  
Vol 19 (8) ◽  
pp. 1165-1169 ◽  
Author(s):  
Linda M. Kampschreur ◽  
Jan Jelrik Oosterheert ◽  
Andy I. M. Hoepelman ◽  
Peter J. Lestrade ◽  
Nicole H. M. Renders ◽  
...  
Keyword(s):  
High Risk ◽  
Phase I ◽  
Q Fever ◽  
Risk Groups ◽  
Valve Surgery ◽  
Cardiac Valve ◽  
Content Type ◽  
Cardiac Valve Surgery ◽  
Chronic Q Fever ◽  
History Of

ABSTRACTChronic Q fever develops in 1 to 5% of patients infected withCoxiella burnetii. The risk for chronic Q fever endocarditis has been estimated to be ∼39% in case of preexisting valvulopathy and is potentially even higher for valvular prostheses. Since 2007, The Netherlands has faced the largest Q fever outbreak ever reported, allowing a more precise risk estimate of chronic Q fever in high-risk groups. Patients with a history of cardiac valve surgery were selected for microbiological screening through a cardiology outpatient clinic in the area where Q fever is epidemic. Blood samples were analyzed for phase I and II IgG againstC. burnetii, and if titers were above a defined cutoff level,C. burnetiiPCR was performed. Chronic Q fever was considered proven ifC. burnetiiPCR was positive and probable if the phase I IgG titer was ≥1:1,024. Among 568 patients, the seroprevalence ofC. burnetiiantibodies (IgG titer greater than or equal to 1:32) was 20.4% (n= 116). Proven or probable chronic Q fever was identified among 7.8% of seropositive patients (n= 9). Valve characteristics did not influence the risk for chronic Q fever. Patients with chronic Q fever were significantly older than patients with past Q fever. In conclusion, screening of high-risk groups is a proper instrument for early detection of chronic Q fever cases. The estimated prevalence of chronic Q fever is 7.8% among seropositive patients with a history of cardiac valve surgery, which is substantially higher than that in nonselected populations but lower than that previously reported. Older age seems to increase vulnerability to chronic Q fever in this population.

Picture Recognition Errors in the Differential Diagnosis of Alzheimer’s Disease

2019 ◽  
Vol 30 (3) ◽  
pp. 157-168
Author(s):  
Helmut Hildebrandt ◽  
Jana Schill ◽  
Jana Bördgen ◽  
Andreas Kastrup ◽  
Paul Eling
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Differential Diagnosis ◽  
Clinical Diagnosis ◽  
Response Bias ◽  
Recognition Task ◽  
Discriminatory Power ◽  
False Alarms ◽  
Picture Recognition ◽  
Recognition Errors

Abstract. This article explores the possibility of differentiating between patients suffering from Alzheimer’s disease (AD) and patients with other kinds of dementia by focusing on false alarms (FAs) on a picture recognition task (PRT). In Study 1, we compared AD and non-AD patients on the PRT and found that FAs discriminate well between these groups. Study 2 served to improve the discriminatory power of the FA score on the picture recognition task by adding associated pairs. Here, too, the FA score differentiated well between AD and non-AD patients, though the discriminatory power did not improve. The findings suggest that AD patients show a liberal response bias. Taken together, these studies suggest that FAs in picture recognition are of major importance for the clinical diagnosis of AD.

scholarly journals Contributions of lipopolysaccharide and the type IVB secretion system to Coxiella burnetii vaccine efficacy and reactogenicity

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Carrie M. Long ◽  
Paul A. Beare ◽  
Diane C. Cockrell ◽  
Jonathan Fintzi ◽  
Mahelat Tesfamariam ◽  
...  
Keyword(s):  
Phase I ◽  
Coxiella Burnetii ◽  
Vaccine Efficacy ◽  
Q Fever ◽  
Secretion System ◽  
Cell Vaccine ◽  
Post Vaccination ◽  
Whole Cell Vaccine ◽  
Type Ivb Secretion ◽  
Type Ivb Secretion System

AbstractCoxiella burnetii is the bacterial causative agent of the zoonosis Q fever. The current human Q fever vaccine, Q-VAX®, is a fixed, whole cell vaccine (WCV) licensed solely for use in Australia. C. burnetii WCV administration is associated with a dermal hypersensitivity reaction in people with pre-existing immunity to C. burnetii, limiting wider use. Consequently, a less reactogenic vaccine is needed. Here, we investigated contributions of the C. burnetii Dot/Icm type IVB secretion system (T4BSS) and lipopolysaccharide (LPS) in protection and reactogenicity of fixed WCVs. A 32.5 kb region containing 23 dot/icm genes was deleted in the virulent Nine Mile phase I (NMI) strain and the resulting mutant was evaluated in guinea pig models of C. burnetii infection, vaccination-challenge, and post-vaccination hypersensitivity. The NMI ∆dot/icm strain was avirulent, protective as a WCV against a robust C. burnetii challenge, and displayed potentially altered reactogenicity compared to NMI. Nine Mile phase II (NMII) strains of C. burnetii that produce rough LPS, were similarly tested. NMI was significantly more protective than NMII as a WCV; however, both vaccines exhibited similar reactogenicity. Collectively, our results indicate that, like phase I LPS, the T4BSS is required for full virulence by C. burnetii. Conversely, unlike phase I LPS, the T4BSS is not required for vaccine-induced protection. LPS length does not appear to contribute to reactogenicity while the T4BSS may contribute to this response. NMI ∆dot/icm represents an avirulent phase I strain with full vaccine efficacy, illustrating the potential of genetically modified C. burnetii as improved WCVs.

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