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Autoantibody profiles in the sera of patients with Q fever: characterization of antigens by immunofluorescence, immunoblot and sequence analysis.

Recent reports have shown that some of the immunological aspects of Q fever, a rickettsiosis caused by Coxiella burnetii, could be related to self-antigen responses. The aim of this study was to determine the specificity of the autoantibody response of patients with acute and chronic Coxiella infections. Smooth muscle and cardiac muscle-specific autoantibodies were observed in significant percentages in acutely or chronically affected Q fever patients when compared to healthy volunteers. Moreover, the incidence of cardiac muscle-specific autoantibody was significantly higher among chronically ill patients compared to acutely ill patients. Moreover, a band of 50 kD of a HeLa extract was detected in most of the sera of individuals with chronic infections and previous sequence analysis suggests that this antigen presents a high degree of homology with the human actin elongation factor 1 alpha. Further research would be necessary to confirm if antibodies to human cytoskeletal proteins could be of clinical importance in chronically infected Q fever patients.

Journal Article↗

Serodiagnosis of Q fever by enzyme-linked immunosorbent assay (ELISA).

Indirect enzyme-linked immunosorbent assays (ELISAs) specific for IgG and IgM antibodies against Coxiella burnetii were applied to test 208 serum samples collected within 1983 to 1986 from 128 individuals suspected of having Q fever, and from 1611 serum samples of normal blood donors. Among them were 2 patients with Q fever endocarditis, one patient with myocarditis, one patient with chronic hepatitis, 3 patients with pneumonia, one woman who had aborted a monstrous child, 38 state veterinarians, 26 farms workers, 21 persons employed in veterinary medicine, and 4 laboratory workers. Comparison with the complement fixation test (CF) revealed 46 (38%) subjects seropositive by CF and 77 (60%) seropositive by IgG and/or IgM ELISA. Among the normal blood donors 22% had antibodies to C. burnetii by ELISA. With exception of two CF titers of 1:2 and 1:8, all positive results detected by CF were confirmed by ELISA. Early stages of C. burnetii infections could be diagnosed in four cases with a single serum sample through demonstration of specific IgM by ELISA before appearance of CF antibodies. In 9 patients with acute Q fever and rising CF titers or IgG levels, diagnosis was already possible with the first serum sample by demonstration of high IgM levels by ELISA. In the two cases of endocarditis investigated, high CF titers against phase I antigen of C. burnetii confirmed the diagnosis "chronic Q fever".

Antibodies, Bacterial↗

Cynomolgus monkey model for experimental Q fever infection.

A subhuman primate model was developed for study of the pathogenesis of infection with Coxiella burnetii. Cynomolgus monkeys (Macaca fascicularis) that were exposed to 10(5) mouse median infectious intraperitoneal doses of C. burnetii in a small-particle aerosol developed clinical signs of illness and pathologic changes characteristic of Q fever infection in humans. All monkeys had radiologic evidence of pneumonia by day 9. Antibodies to C. burnetii were detectable by the indirect fluorescent antibody test by day 7. These data indicate that the cynomolgus monkey is a suitable model for study of the pathogenesis of Q fever infection and may prove valuable in the evaluation of C. burnetii vaccines.

Aerosols↗

Fat of Coxiella burnetti in macrophages from immune guinea pigs.

The interaction between Coxiella burnetii and peritoneal macrophages obtained from immune guinea pigs was studied by transmission electron microscopy. Phagocytosis and subsequent fate of ingested phase I and II rickettsiae were compared. Phase I rickettsiae were more resistant to phagocytosis than were phase II organisms. Macrophages from phase I- and II-immunized animals were equally capable of phagocytizing rickettsiae. Phase I and II rickettsiae previously treated with normal serum multiplied and destroyed macrophages from guinea pigs that had been immunized with phase II rickettsiae. Phase II organisms were initially suppressed in macrophages from phase I-immunized animals, but eventually multiplied in these cells. In contrast, only phase I organisms were destroyed by macrophages from phase I-immunized animals. Treatment of rickettsiae with immune serum enhanced ingestion by macrophages and potentiated the destruction of organisms by both types of macrophages. The macrophage migration inhibition assay was performed on peritoneal exudate cells from immune animals. Migration of peritoneal macrophages from phase I-immunized guinea pigs was inhibited, whereas macrophages from phase II-immunized animals migrated when cells were cultured in the presence of killed, intact phase I or II C. burnetii.

Antibodies, Bacterial↗

Plaque assay for Q fever and scrub typhus rickettsiae.

The plaque assay procedure developed for spotted fever and typhus group rickettsiae is also appropriate for scrub typhus and Q fever rickettsiae. The plaque titers of suspensions of Rickettsia tsutsugamushi and Coxiella burnetii compared favorably with end points obtained by titrations in mice.

Animals↗

'Ring' granulomas in cytomegalovirus hepatitis.

A liver biopsy specimen obtained from a patient with cytomegalovirus hepatitis demonstrated "ring" granulomas similar to those previously described as characteristic of acute Coxiella burnetii infection. Q fever is not the only infectious disease in which fibrinoid rings may form within granulomatous foci.

Adult↗

Infectivity, transmission and 16S rRNA sequencing of a rickettsia, Coxiella cheraxi sp. nov., from the freshwater crayfish Cherax quadricarinatus.

A rickettsia-like organism isolated from infected, farm-reared Cherax quadricarinatus was cultured in the yolk sac of developing chicken eggs, but could not be cultured in 3 continuous cell lines, bluegill fry (BF-2), fathead minnow (FHM), and Spodoptera frugiperda (Sf-9). The organism was confirmed by fulfilling Koch's postulates as the aetiological agent of mortalities amongst C. quadricarinatus. When C. quadricarinatus was inoculated with the organism, mortality was 100% at 28 degrees C and 80% at an ambient temperature of 24 degrees C. Horizontal transmission with food and via the waterborne route was demonstrated, but mortalities were lower at 30 and 10% respectively over a 4 wk period. The 16S rRNA sequence of 1325 base pairs of the Gram-negative, obligate intracellular organism was 95.6% homologous to Coxiella burnetii. Of 18 species compared to this rickettsia, the next most closely related bacterium was Legionella pneumophila at 86.7%. The suggested classification of this organism is Order Rickettsiales, family Rickettsiaceae, tribe Rickettsieae, within the genus Coxiella. We suggest it should be named Coxiella cheraxi sp. nov.

Animals↗

[Study of the reactivity and immunogenicity of a combined vaccine against abortion due to coxiellosis and chlamydiosis in sheep].

Reactogenicity was studied in a combined vaccine against Q-fever and chlamydia-induced abortion in ewes; the vaccine consisted of a mixture of purified corpuscles of Chlamydia psittaci (100 micrograms) and Coxiella burnetii (50 micrograms). The immunogenicity of the combined vaccine, evaluated by the number of positive serums after vaccination and by the average geometric titre of antibodies, was the same as that of the vaccine separate constituents as to the antibodies to C. burnetii, but somewhat higher in the case of antibodies to Chlamydia psittaci. When studied on a smaller number of ewes, the combined vaccine had an optimum immunogenicity in the cases of the prevalence of Chlamydia psittaci over C. burnetii in the vaccine.

Abortion, Veterinary↗

Exposure to parturient cats: a risk factor for acquisition of Q fever in Maritime Canada.

Over a 34-mo period we studied 51 patients with Q fever and 102 control subjects (with various lower-respiratory-tract infections) who were matched for age, sex, and time of onset of infection. By univariate analysis (not adjusted for multiple comparisons), cases differed significantly from controls in the following activities: working on a farm; slaughtering or dressing animals; and contact with cats, cattle, and sheep. The strongest association was with exposure to stillborn kittens--11 of 51 cases vs. none of 102 controls (P less than .00000)--and with exposure to parturient cats (odds ratio, 10.3; 95% confidence interval, 3.5-31.8). Exposures to newborn animals (chiefly kittens) and stillborn kittens were significant risk factors by multivariate analysis, as were rural residence and slaughtering or dressing animals. In 13 Q fever incidents following exposure to parturient cats, 80 people became ill, 52 of whom had serological evidence of recent Coxiella burnetii infection (most of the others were not tested).

Animals↗

[Q fever in Guinea-Bissau. 1 case].

Q fever is seldom reported in West Africa. The case of a man returning from Guinea Bissau who presented an acute lobar pneumonia with fever, headache, hematuria and hepatitis was confirmed by high titers of antibody in Phase II indirect immuno-fluorescence which appeared on the twelfth day of fever. Treatment with erythromycin was continued by doxycyclin, and complete resolution of all signs was promptly obtained. Coxiella Burnetii might thus be responsible of cases of unexplained fever with respiratory or hepatic manifestations in West Africa.

Antibodies, Bacterial↗

Epidemiology (1980-1985) and nonspecific prophylaxis of Q fever in the USSR (survey).

A review of the epidemiology and nonspecific prophylaxis of Q fever in the USSR during 1980-1985 is presented. Attention is paid of the source to infection, the seroprevalence of antibodies to Coxiella burnetii in man and livestock and the possibilities of prophylaxis against Q fever under conditions of mandatory registration of this disease.

Animals↗

Serological study with rickettsial antigens in erythema chronicum migrans.

21 sera of 13 patients with erythema chronicum migrans (ECM) and related diseases were examined for the presence of antibodies against 14 rickettsial antigens by using 3 serological techniques in 2 laboratories. Most tests were negative. This indicates that ECM and related diseases are not due to an hitherto known rickettsia. 5 out of 158 tests showed, however, positive reactions in low titers against Rickettsia akari and Coxiella burnetii. Thus, an antigenic relationship may exist between one or more rickettsia(e) and the etiologic agent of ECM.

Antibodies, Bacterial↗

Human pathogen subversion of antigen presentation.

Many pathogens have co-evolved with their human hosts to develop strategies for immune evasion that involve disruption of the intracellular pathways by which antigens are bound by class I and class II molecules of the major histocompatibility complex (MHC) for presentation to T cells. Here the molecular events in these pathways are reviewed and pathogen interference is documented for viruses, extracellular and intracellular bacteria and intracellular parasites. In addition to a general review, data from our studies of adenovirus, Chlamydia trachomatis and Coxiella burnetii are summarized. Adenovirus E19 is the first viral gene product described that affects class I MHC molecule expression by two separate mechanisms, intracellular retention of the class I heavy chain by direct binding and by binding to the TAP transporter involved in class I peptide loading. Coxiella and Chlamydia both affect peptide presentation by class II MHC molecules as a result of their residence in endocytic compartments, although the properties of the parasitophorous vacuoles they form are quite different. These examples of active interference with antigen presentation by viral gene products and passive interference by rickettsiae and bacteria are typical of the strategies used by these different classes of pathogens, which need to evade different types of immune responses. Pathogen-host co-evolution is evident in these subversion tactics for which the pathogen crime seems tailored to fit the immune system punishment.

Animals↗

Serological evidence of Q fever in cattle in Malawi.

The serological prevalence of Coxiella burnetii in cattle in Malawi is unknown. Serum samples from 200 Malawian zebu cattle were tested for C. burnetii antibodies using the complement fixation test. The percentage of positive and suspicious titres was 1.5% and 5% respectively.

Animals↗

Epidemiology of Q fever in Sweden.

Q fever is known to be a worldwide disease, with Sweden supposed to be one of a few exceptions. The purpose of this pilot study was to elucidate whether or not a potential risk group for obtaining Q fever in Sweden was seropositive to the causative agent Coxiella burnetii. Blood samples were collected from sheep farmers on the island of Gotland, and from members of their families. Serum samples were examined by ELISA for the presence of antibodies against C. burnetii, phases I and II. Positive reactions were confirmed with Western blot analysis. It was found that 30% of the study group were seropositive to C. burnetii, thus indicating that Q fever is endemic in this area of Sweden.

Adolescent↗

Q fever in Sokoto, Nigeria.

There is very little information available about the prevalence of Coxiella burnetii in Africa. We obtained blood from 75 Nigerians hospitalized in Sokoto for a variety of acute medical conditions. Their age range was 7 months to 50 years; there were 39 males and 36 females. Antibody titers were determined to phase I and phase II C. burnetii antigens using a microimmunofluorescence test. Thirty-three (44%) had an antibody titer of greater than or equal to 1:8 to phase II C. burnetii. We conclude on the basis of this limited survey that Q fever is common in Nigeria.

Adolescent↗

[Coexistence of Legionnaires' disease and Q fever in a single patient].

A case of Legionnaires' disease associated with Q fever is presented; this is probably the first reported case of concomitant infections with Legionella pneumophila and Coxiella burnetii. The pulmonary features of the illness were not typical of either disease. The difficulties of making a diagnosis in such cases are discussed.

Adult↗

Nucleotide sequence of htpB, the Legionella pneumophila gene encoding the 58-kilodalton (kDa) common antigen, formerly designated the 60-kDa common antigen.

Gene htpB, which encodes the 58-kilodalton protein of Legionella pneumophila, was cloned in Escherichia coli and its complete nucleotide sequence was determined. Analysis of this sequence revealed an open reading frame of 1,644 nucleotides encoding a protein with a predicted molecular mass of 57,952 daltons. Data obtained by amino-terminal sequencing of the purified 58-kilodalton protein agreed, except for one amino acid residue, with the predicted amino acid sequence, identifying this open reading frame as htpB. A comparison of the primary structure of this protein to other proteins of similar molecular weights from E. coli, Mycobacterium leprae, M. tuberculosis, and Coxiella burnetii revealed significant regions of sequence similarity, which are discussed.

Amino Acid Sequence↗