Proteus OX19 Research Articles

A Rare Case of Rickettsia and Herpes Simplex Virus 1 Co-infection in a Male Patient with Meningoencephalitis

Herpes simplex viruses (HSVs) belong to the Herpesviridae family. Close contact is the primary mode of transmission for both HSV-1 and HSV-2, leading to a persistent lifelong infection. HSVs are widely recognized as causative agents of viral infections affecting the central nervous system, capable of presenting as both meningitis and encephalitis. Herpes simplex virus type 1 (HSV-1) is the predominant viral cause of encephalitis, accounting for the majority of cases. Here, a rare co-infection case of meningoencephalitis, associated with HSV-1 and rickettsia is described. A 42-year-old man presenting with non-remitting headache for 6 days, fever, sweating, and muscle aches was admitted to the Emergency Department. His Weil-Felix test was positive for Proteus OX2 indicating rickettsial infection. Therapy started promptly however patient’s condition deteriorated. Cerebrospinal fluid (CSF) analysis revealed lymphocytic pleocytosis, and elevated protein concentration. CSF molecular analysis was positive for HSV-1. His cranial MRI indicated cytotoxic edema and gyral enhancement at the right temporal lobe. He was administered acyclovir for 14 days during hospital stay and was successfully discharged. This case report highlights that HSV-1 meningoencephalitis can co-occur with rickettsia infection in immunocompetent individuals, and co-infection with other agents should always be considered to avoid the progression of the disease.

Could the SARS-CoV-2 Outbreak Cause an Increase in Rickettsia Infection? North Cyprus Observation

Objective: The aim of the study was to determine the prevalence rate of the Rickettsiae infection during the Turkish Republic of North Cyprus SARS-CoV-2 pandemic according to years.Methods: This cross-sectional study was carried out during 2016 to 2020. Weil-Felix test is based on cross-reactions which occur between antibodies produced in acute rickettsial infections with antigens of OX (OX 19, OX 2, and OXK) strains of Proteus species. On a lam surface, a small 100 μL of the patient’s serum is placed. A single drop of the desired antigen (OX19, OX2 ve OXK) is added, and the resulting suspension is mixed and then rotated for one minute. Visible agglutination is indicative of a positive result and corresponds roughly to a titer of 1:20. Statistical analysis of the data obtained was conducted with SPSS (Statistical Package for the Social Sciences) Demo Ver 22.0 (SPSS Inc., Chicago, IL, USA) program.Results: Total patient number were 369 (Male: 192, 52%; Female: 177, 48%) and the mean age was 33.40±21.37. The number of patients who found as positive for any of the Rickettsiae infection (OX19, OX2 and OXK) were 15.4% in 2016; 21.1% in 2017; 22.9% in 2018 %; 23% in 2019 and 37.3% in 2020. It has been observed that OX19 and OX2 positivity has increased significantly over the years. It is seen that the Proteus OX19 positive cases in 2020 are significantly higher than in other years (p=0.026). It is found that the positive cases of OX2 positivity in 2020 are significantly higher than in other years (p=0.036). Additionaly, considering the distribution over the years, it was seen that Rickettsiae positive patients increased significantly between 2016 and 2020 (p=0.017). Additionaly, considering the distribution over the years, it was seen that Rickettsiae positive patients increased significantly between 2016 and 2020 (p=0.017).Conclusion: Our hypothesis is the because of the SARS-CoV-2 pandemic due to the people staying at home the animal population such as rodents’ population caused an increase. Therefore, the increase in zoonotic infections should not be ignored and it should not be forgotten that necessary precautions should be taken to prevent these infections from getting out of control.

A study on serodiagnosis of scrub typhus in a Teaching Hospital of South India

Background: crub typhus is caused by Orientia tsutsugamushi (rickettsial disease) commonly transmitted by the bite of larval chiggers of trombiculid mites. It has been one of the important causes of febrile illness, especially in south India. The clinical diagnosis is difficult owing to the non-specific presentation. We in the current study tried to evaluate the serodiagnosis of scrub typhus with the Weil Felix test and IgM ELISA. Methods: This study was conducted in the Department of Microbiology, Prathima Institute of Medical Sciences, Naganoor, Karimnagar. All the sera samples were subjected to the Weil Felix test using Proteus OX2, OX19, OX-K strain agglutination test, and subsequently, Scrub typhus IgM ELISA test. Results: All the samples were subjected to the Weil Felix test n=4(6.06%) were positive for scrub typhus (OXK antigen) n=11(16.67%) were positive for the spotted group of fever (OX2 antigen) and n=10 (15.15%) were positive of typhus group (OX19 antigen). N=5 sera samples were positive for more than one type of antigens. All the n=66 serum samples were subjected to IgM ELISA for scrub typhus. Out of n=66, only two serum samples (3.03%) were positive by IgM ELISA. Conclusion: Scrub typhus is emerging as an important public health issue. It is one of the important causes of acute febrile illness. Although it is difficult to distinguish scrub typhus based on the clinical symptoms alone a simple test such as Weil Felix was found to be promising in the diagnosis of scrub typhus. ELISA IgM test may be performed additionally in laboratories with adequate facilities. Hence for clinicians, any case with a fever of unknown origin should arouse suspicion of scrub typhus

Synthesis and biological activity of new cycloalkylthiophene-Schiff bases and their Cr(III) and Zn(II) complexes

A series of some novel Ethyl 2-((1-hydroxynaphthalen-2-yl)methyleneamino)-5,6-dihydro-4H-cyclopenta[b]thiopehene-3-carboxylate, Ethyl 2-((1-hydroxynaphthalen-2-yl)methyleneamino)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate, Ethyl 2-((1-hydroxynaphtalen-2-yl)methyleneamino)-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxylate and their Cr(III) and Zn(II) complexes have been synthesized. All of these substances have been examined for antibacterial activity against pathogenic strains Listeria monocytogenes 4b (ATCC-19115), Staphylococcus aureus (ATCC25923), Proteus OX2 Wrah (ETS.40-A-4), Escherichia coli (ATCC-1280), Salmonella typhi H (NCTC-901.8394), Pseudomonas putida sp., Brucella abortus (A.99, UK-1995) RSKK-03026. Sh. boydii type 11 (Pasteur51.6), Sh. boydii type 16 (cHe 67.11), Sh. boydii type 6 (RSKK-96043), and antifungal activity against Candida albicans (Y-1200-NIH, Tokyo). Some of the compounds exhibited activity comparable to ampicillin ofloxacin, nystatin, kanamycin, sulphamethoxazol, amoxycillin, and chloroamphenicol. Most of the studied compounds were found effective against bacteria studied and yeast.

Helicobacter pylori: An Underestimated Factor in Acute Anterior Uveitis and Spondyloarthropathies?

Acute anterior uveitis (AAU) is the most common form of intraocular inflammation, but its aetiology is still unclear. Fifty percent of AAU patients are HLA-B27-positive, and half of these also have spondyloarthropathies (SpA). Numerous serological studies have shown elevated levels of serum antibodies to various Gram-negative bacteria in HLA-B27-positive AAU and SpA patients. Antigenic similarities between these bacteria and host components (HLA-B27) have already been shown. Still, the mechanism underlying these diseases has not been clarified. Among the Gram-negative bacteria, Helicobacter pylori has not been screened in AAU patients. The purpose of our study was to see if this common human pathogen somehow interferes with AAU. In addition Chlamydia trachomatis, Yersinia enterocolitica 03 and 09, Salmonella sp. and Proteus OX19 were also examined. A total of 60 patients consisting of 4 groups (15 patients with AAU, 15 with SpA, 15 with AAU+SpA and 15 healthy control persons) were examined. A high percentage of the serological results of all investigated bacteria was positive: 80% in the AAU, 93.3% in the SpA and 100% in the AAU+SpA group, while it amounted to 66.7% in the control group (p < 0.05). H. pylori showed the highest percentage of positivity in all 3 patient groups (66.7% in the AAU, 73.3% in the SpA and 80% in the AAU+SpA group). In contrast, 26.7% of the controls were anti-H.-pylori-positive, thus showing a statistically significant difference between the patients and the control group (p < 0.05). HLA-B27/B7-CREG positivity was detected in 53.3% of the AAU, 66.7% of the SpA and 93.3% of the AAU+SpA patients and in none of the controls. Our results suggest that H. pylori might be a candidate participating in the development of AAU and SpA. They also support the theory of genetic (HLA-B27) and exogenous factors (Gram-negative bacteria) as probable background of these diseases.

Serologic evidence of human infection by Francisella tularensis in the population of Castilla y León (Spain) prior to 1997

Prior to an outbreak in Castilla y León in December 1997, tularaemia was practically non-existent in Spain. In this paper we studied the prevalence of antibodies against Francisella tularensis in a representative sample of the population (4825 people) from Castilla y León (Spain) in samples collected before this outbreak. Antibodies against F. tularensis were detected in nine (0.19%) of the 4825 sera, with antibody titres ranging from 1/20 to 1/160. Of these nine sera, one was positive in seroagglutination against Brucella. Seroagglutination against other bacteria ( Yersinia enterocolitica O:9 and O:3 and Proteus OX19) was negative in all sera. Seroprevalence of antibodies in females was 0.20% and 0.17% in males; no statistically significant differences were found in prevalence in terms of sex, age or province.

Presence ofRickettsia helveticain Granulomatous Tissue from Patients with Sarcoidosis

In samples obtained during the autopsies of 2 patients with sarcoidosis, genetic material from Rickettsia helvetica was detected by polymerase chain reaction, and histologic and immunohistochemical examination (using 3 different antibodies) of the polymerase chain reaction-positive tissues showed different degrees of granuloma formation and presence of rickettsia-like organisms predominantly located in the endothelium and macrophages. Electron microscopic examination clearly identified and demonstrated rickettsia-like organisms within the granuloma, with findings suggestive of ongoing infection. Immunogold labeling with Proteus OX-19 antiserum showed that the gold markers were localized to the rickettsia-like organisms. Paraffin-embedded biopsy specimens from 30 patients with confirmed sarcoidosis were also reexamined, and 26 specimens were judged to be positive for rickettsia-like organisms by histologic and immunohistochemical examination. In a specimen from 1 patient, rickettsia-like organisms also were demonstrated and identified by transmission electron microscopy. These results support the hypothesis that rickettsiae may contribute to a granulomatous process, as is seen in sarcoidosis.

Association of Rickettsia helvetica with chronic perimyocarditis in sudden cardiac death

Rickettsia helvetica is the only non-imported rickettsia found in Scandinavia. It was first detected in Ixodes ricinus ticks, but has never been linked to human disease. We studied two young Swedish men who died of sudden cardiac failure during exercise, and who showed signs of perimyocarditis similar to those described in rickettsial disease. Samples from the heart and other organs were analysed by PCR and DNA sequencing. May-Grünwald-Giemsa, Grocott, and acridine-orange stains were used for histopathological examinations. Staining of R. helvetica grown on shell-vials in vero cells, and the early descriptions of R. rickettsii by H T Ricketts and S B Wohlbach served as controls. Immunohistochemistry was done with Proteus OX-19 rabbit antisera as the primary antibody. The structure of rickettsia-like organisms was investigated by transmission electron microscopy. Serological analyses were carried out by indirect immunofluorescence with R. helvetica as the antigen. By use of a semi-nested PCR, with primers specific for the 16S rRNA and 17-kDa outer-membrane-protein genes, and sequence analysis of the amplified products, genetic material from R. helvetica was detected in the pericardium and in a lymph node from the pulmonary hilum in case 1, and in a coronary artery and the heart muscle in case 2. A serological response in case 1 revealed an endpoint titre for R. helvetica of 1/320 (1/256 with R. rickettsii as the antigen). Examination of PCR-positive tissue showed chronic interstitial inflammation and the presence of rickettsia-like organisms predominantly located in the endothelium. These organisms reacted with Proteus OX-19 antisera, and their size and form were consistent with rickettsia. Electron microscopy confirmed that the appearance of the organisms was similar to that described for spotted-fever rickettsia. R. helvetica, transmitted by I. ricinus ticks, may be an important pathogen in the aetiology of perimyocarditis, which can result in sudden unexpected cardiac death in young people.

Vaginal Mucositis in Measles

Background: Measles (rubeola), a common childhood exanthema, occurs infrequently in adults. Vaginal mucositis in association with measles is not commonly described. Case: During a recent measles epidemic, 2 female patients presented with high fever, myalgia, exanthema, and prostration. On examination, each patient had marked inflammation and tenderness of the vaginal mucosa, prompting the presumptive diagnosis of toxic shock syndrome. The evolution of the illness was consistent with measles. Cervicovaginal cultures were negative for pathogens. Acute and convalescent antibody titers for Rocky Mountain spotted fever, rubella, leptospirosis, and Proteus Ox-19 were not consistent with a recent infection. The sera also were negative for anti-toxic shock toxin-1 and anti-streptolysin. Measles antibody titers were consistent with a recent infection. Conclusion: Vaginal mucositis is an unusual manifestation of measles that may mimic toxic shock syndrome.

Immunological properties of Weil-Felix test negative sera from patients with Japanese spotted fever

Sera from 4 out of 19 patients with the Japanese spotted fever were negative to OX2 antigen of Weil-Felix (WF) test. These WF test negative sera were analyzed by ELISA and immunoblot used whole cells and lipopolysaccharides (LPS) of rickettsiae and Proteus strains as antigens. These acute-phase sera have already possessed the IgG antibodies against LPS of Proteus OX2 strain, whereas IgM antibodies in these acute- and convalescent-phase sera did not react with this LPS. On the other hand, the reactivity of IgM antibodies of the convalescent-phase sera in the 2 patients with LPS of Proteus OX19 strain increased as compared with that of the acute-phase sera by ELISA, and these IgM antibodies also showed the reactivity with bands of OX19-LPS in the immunoblot. On the basis of these results, it is interpreted that the WF test negative sera from patients with Japanese spotted fever are due to the presence of IgG antibodies against OX2-LPS in the sera.

Immunological Characterization of Lipopolysaccharides from Proteus Strains Used in Weil‐Felix Test and Reactivity with Patient Sera of Tsutsugamushi Diseases

Immunological analyses of lipopolysaccharides (LPS) isolated from Proteus strains OX2, OX19, and OXK used as antigens of Weil-Felix (WF) test, were performed by quantitative agglutination, enzyme-linked immunosorbent assay (ELISA), and immunoblotting. Antisera against LPS and whole cells (WC) of the three Proteus strains reacted with homologous LPS but not with heterologous LPS, and the reaction was inhibited by the O-polysaccharide fraction isolated from the homologous LPS except OX19-LPS, which lacked O-polysaccharide moiety. The immunological data support the findings that the O-polysaccharide moieties of LPS from OX2 and OXK strains possess different chemical composition (Mizushiri, Amano, Fujii, Fukushi, and Watanabe, Microbiol. Immunol. 34: 121-133, 1990). Antisera against Proteus strains reacted weakly with WC of Rickettsia prowazekii, Rickettsia typhi, and Rickettsia tsutsugamushi. Antisera from patients with tsutsugamushi disease reacted with OXK-WC by WF test when the sera were obtained 13 days after onset of fever. The immunoperoxidase (IP) test titers of these antisera began to rise 6 days after the onset of fever. By ELISA tests these antisera reacted with OXK-WC and OXK-LPS independently of the titers of WF or IP tests.

Chemical Characterization of Lipopolysaccharides from Proteus Strains Used in Weil‐Felix Test

The lipopolysaccharides (LPS) extracted from Proteus strains OX2, OX19, and OXK used as antigens in the Weil-Felix test, were characterized by chemical analysis and SDS-polyacrylamide gel electrophoresis (SDS-PAGE). To separate the O-polysaccharide, core-oligosaccharide, and lipid A moieties, each LPS was treated with 2% acetic acid, centrifuged, and applied to Sephadex G-50 column. The core-oligosaccharides contained L-glycero-D-mannoheptose, D-glycero-D-mannoheptose, glucose (Glc), galactose, 3-deoxy-D-mannooctulosonic acid, uronic acid, phosphate, glucosamine (GlcN), and galactosamine (GalN). The lipid A preparations contained GlcN, GlcN-phosphate, and three fatty acids (myristic, plamitic, and beta-hydroxymyristic acids). However, the O-polysaccharides of OX2- and OXK-LPS had different chemical compositions which consisted of Glc, GlcN, and quinovosamine, and Glc, uronic acid, and GalN, respectively, while OX19-LPS seemed to lack O-polysaccharide.

淡路島地方における紅斑熱群リケッチア症

Three cases of spotted fever group rickettsiosis occurring on Awaji Island, Hyogo Prefecture, the first reported in the Kinki District, are described. The illness appeared from August to September in 1988. High-grade fever and papular erythema were observed in all cases. Eschar, lymphadenopathy and hepatomegaly were observed in two-thirds of the cases, respectively. The antibody titers for Proteus OX-2 by the Weil-Felix reaction were elevated, and immunofluorescence test with R. rickettsii of the spotted fever group demonstrated a significant rise in specific antibody titer. Tetracycline was effective in all cases. Every patient was thought to have been infected with rickettsiae in the Yuzuruha mountain range in the southern part of Awaji Island. On the other hand, tsutsugamushi disease occurs in autumn and winter in the northern part of Awaji Island. It would be of considerable interest from an epidemiological viewpoint to study the vector of these spotted fever group rickettsiae.

Boutonneuse fever transmitted by conjunctival inoculation

We report three cases (two adult males and a 12-year-old child) of boutonneuse fever produced by inoculation of the conjunctival mucosa (probably through accidental entry of R. conorii fluid into the eyes through rubbing or splashing). All three patients developed similar symptoms of disease, including high fever, headache, maculopapular exanthem, and conjunctivitis, and none had tache noire. Specific immunofluorescent antibodies appeared in these patients' serum mostly after the 2nd week; agglutinins to Proteus OX-19, OX-2 (Weil-Felix reaction) were found. Cure was obtained by oral tetracycline. Conjunctival inoculation of R. conorii producing boutonneuse fever is very rare; this report will probably be one of the first published in the medical literature.

The Sensitivity of Various Serologic Tests in the Diagnosis of Rocky Mountain Spotted Fever

Sensitivity indices for various serologic tests in the diagnosis of Rocky Mountain spotted fever (RMSF) were determined from RMSF surveillance data collected at the Centers for Disease Control (CDC) during 1981-1984. During these 4 years, a total of 4,141 cases of RMSF in the U.S. were reported to CDC. Case report forms, which include information on dates and results of serologic testing, were received for 3,567 of these cases; 1,774 were laboratory-confirmed according to criteria published previously by CDC. Sensitivity indices for the Weil-Felix (Proteus OX-19, OX-2), indirect fluorescent antibody (IFA), latex agglutination (LA), complement fixation (CF) and indirect hemagglutination (IHA) tests were examined by analyzing cases confirmed by other means, in which data concerning the test in question were available. Analysis of serum pairs for a 4-fold or greater increase in antibody titer or a minimum diagnostic titer indicated high sensitivity indices for IHA (96%) and IFA (94%), but lower sensitivity indices for OX-19 (70%), OX-2 (47%), CF (63%) and LA (71%). IFA and IHA appear to be the most sensitive serologic tests currently in use for the diagnosis of RMSF.

Acute rickettsial myocarditis and advanced atrioventricular block: diagnosis and treatment aided by endomyocardial biopsy

A case of acute advanced atrioventricular block in a young patient is described. An endomyocardial biopsy performed to confirm myocarditis showed findings compatible with rickettsial endomyocarditis. Treatment with tetracycline was therefore started and a rapid remission of the atrioventricular block was observed. Healing of the disease was subsequently documented by a second endomyocardial biopsy. The rickettsial etiology was confirmed by the results of serial serum titers against Proteus OX-19. Endomyocardial biopsy may be clinically indicated for the diagnosis of advanced atrioventricular block in young patients and may help in their optimal treatment.

Spotted fever group rickettsiosis in Japan.

The acute febrile disease with characteristic rash encountered in Tokushima Prefecture was proved to be a spotted fever group rickettsiosis, which showed a significant rise in agglutinins to both Proteus OX2 and OX19 and significantly high levels of CF antibodies to Rickettsia akari and Rickettsia rickettsii.

Transient Acquired Immunodeficiency During Rickettsial Disease

To the Editor. —Abnormalities in lymphocyte subpopulations have been reported in patients with acquired immune deficiency syndrome (AIDS) 1-3 and in patients with infections due to viruses and intracellular pathogens. 4-8 We have recently had the opportunity of studying a case of boutonneuse fever during which a transient reduction of helper-suppressor (OKT4-OKT8) ratio was observed (Figure). Report of a Case. —A previously healthy 57-year-old heterosexual male patient was admitted to the hospital with high fever, severe headache, prostration, generalized myalgia, and disseminated macular exanthem that later became petechial. No initial lesion (tache noire) was seen. The diagnosis was established by the appearance of agglutinins to Proteus OX-2 and the specific complement-fixing antibodies (Rickettsia conorii) (Figure). A transient increase of antibodies for Epstein-Barr virus and cytomegalovirus was observed. This finding may be perhaps due to reactivation of latent infections.

Rocky Mountain Spotted Fever

Serological tests for Rocky Mountain spotted fever were performed on single serum specimens from sixth graders from Forsyth County, North Carolina, an area highly endemic for this disease. Five of 508 *.098%) sera were positive (titer greater than or equal to 1:64) using the indirect fluorescent antibody method. Elevated Proteus agglutination antibody titers (greater than 1:160) to OX-19, but not ot OX-2, were common (19.6%) in these children. No correlation of those with positive OX-19 titers could be made with the cases demonstrating elevated indirect fluorescent antibody titers or with a history of urinary tract infection. These data suggest that the increased prevalence of elevated Proteus OX-19 antibody levels makes a single high titer unreliable in the diagnosis of Rocky Mountain spotted fever and that naturally acquired mild or asymptomatic subclinical cases of Rickettsia rickttsii infection occur.

Towards serodiagnosis of Serratia marcescens infections: Examination of sera from noninfected patients and from experimentally infected rabbits for anti-H and anti-O antibodies; S. marcescens O-antigen cross-reactions with those of other enterobacteriaceae

Sera from 100 patients not infected with Serratia marcescens at the time of hospital admission lacked detectable H-immobilizing antibodies against all 20 currently recognized H-antigens of this microorganism. However, various patient sera revealed elevated titers of O-agglutinins against several of the 20 O-antigens of S. marcescens, in particular O-antigens O1, O3, O4, O5, O7, O8, O10, O11, O16, O17, O18, O19, and O20. Rabbit anti-Shigella serogroup B immune serum cross-reacted with S. marcescens O-antigens O1 and O10; anti-Shigella serogroup C serum cross-reacted weakly with S. marcescens O-antigen O8. Conversely, rabbit anti-S. marcescens O1 and O10 immune sera cross-reacted with a clinical isolate of Shigella flexneri. None of the anti-S. marcescens O1-O20 rabbit immune sera reacted with commercial febrile antigens of Salmonella serogroups A, B, C1,2, D, E1,2,3,4, Brucella abortus, Francisella tularensis, and Proteus OX19. However, a reference strain of Salmonella typhi (9;-,-) was agglutinated by anti S. marcescens anti-O8 and O10 sera, a reference strain of S. paratyphi B (4,5;-,-) weakly by anti-S. marcescens O8 serum, and a reference strain of S. paratyphi C (6,8;-,-) by anti-S. marcescens anti-O10 and O16 rabbit immune sera. None of the anti-S. marcescens H-antisera cross-reacted with H-antigens of S. typhi (9;d,-), S. paratyphi A (1,2;a,-), S. paratyphi B (4,5;b,-), S. choleraesuis (6,7;-,1,5), S. typhimurium (4,5;,i,-), and S. enteritidis (9;gm,-). Yersinia enterocolitica reference strain Ye 75 (O1 = O3) was agglutinated weakly by anti-S. marcescens O2 serum, whereas Y. enterocolitica reference strain Ye 373 (OV = O9) cross-reacted with S. marcescens anti-O5 rabbit immune serum. Intravenously and tissue cage-infected rabbits developed anti-Hand anti-O antibodies within 5 to 12 days after infection with representative test strains of S. marcescens. Therefore, it is suggested that the serodiagnosis of human S. marcescens infections consist of serial monitoring of both anti-H and anti-O agglutinins, because determinations of the latter alone might yield false-positive, i.e., potentially misleading results.