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PubMed1984

Infectious diseases of travelers and immigrants.

Many tropical and other unusual infections can occur in travelers or among foreign-born persons who have emigrated to the United States. The approach to the differential diagnosis includes considering the patient's geographic history, dates of travel, and clinical presentation, along with the geographic distribution and possible incubation periods of suspected pathogens. Important considerations include malaria, typhoid fever, rickettsial disease, dengue, brucellosis, tuberculosis, and leptospirosis. Traveler's diarrhea and dysentery are also common.

Bacterial Infections↗
PubMed1997

Afipia clevelandensis antibodies and cross-reactivity with Brucella spp. and Yersinia enterocolitica O:9.

Afipia clevelandensis is a recently described gram-negative bacterium whose potential pathogenic role in human disease is under investigation. Only one strain, from the pretibial lesion of a patient hospitalized with necrotizing pancreatitis for 5 months, has been isolated. Using an indirect immunofluorescence assay to detect anti-A. clevelandensis antibodies, we found a seroprevalence of 1.5% among 30,194 sera routinely submitted for laboratory diagnosis of rickettsial diseases. However, among the 52 patients who were clinically evaluable and who exhibited detectable antibodies against A. clevelandensis, 42% were eventually diagnosed as certainly or probably having brucellosis and 15% were eventually diagnosed as certainly or probably having Yersinia enterocolitica O:9 infection, which is the serotype most often encountered in Europe. Western immunoblotting and cross-adsorption tests showed that an 11.5-kDa proteinase K-labile band and a 21-kDa proteinase-stable band, presumably lipopolysaccharide, were responsible for cross-reactivity among A. clevelandensis, Brucella abortus, and Y. enterocolitica O:9. Other diagnoses included nosocomial infections and various community-acquired diseases for which the role of A. clevelandensis remains undefined. Physicians and clinical microbiologists should be aware of this cross-reactivity in future assessments of the role of A. clevelandensis in human pathology.

Aged↗
PubMed2005

Some lessons from Rickettsia genomics.

Sequencing of the Rickettsia conorii genome and its comparison with its closest sequenced pathogenic relative, i.e., Rickettsia prowazekii, provided powerful insights into the evolution of these microbial pathogens. However, advances in our knowledge of rickettsial diseases are still hindered by the difficulty of working with strict intracellular bacteria and their hosts. Information gained from comparing the genomes of closely related organisms will shed new light on proteins susceptible to be targeted in specific diagnostic assays, by new antimicrobial drugs, and that could be employed in the generation of future rickettsial vaccines. In this review we present a detailed comparison of the metabolic pathways of these bacteria as well as the polymorphisms of their membrane proteins, transporters and putative virulence factors. Environmental adaptation of Rickettsia is also discussed.

Amino Acid Sequence↗
PubMedDate not supplied

Illness in returned travelers and immigrants/refugees: the 6-year experience of two Australian infectious diseases units.

BACKGROUND: Data comparing returned travelers and immigrants/refugees managed in a hospital setting is lacking. METHODS: We prospectively collected data on 1,106 patients with an illness likely acquired overseas who presented to two hospital-based Australian infectious diseases units over a 6-year period. RESULTS: Eighty-three percent of patients were travelers and 17% immigrants/refugees. In travelers, malaria (19%), gastroenteritis/diarrhea (15%), and upper respiratory tract infection (URTI) (7%) were the most common diagnoses. When compared with immigrants/refugees, travelers were significantly more likely to be diagnosed with gastroenteritis/diarrhea [odds ratio (OR) 8], malaria (OR 7), pneumonia (OR 6), URTI (OR 3), skin infection, dengue fever, typhoid/paratyphoid fever, influenza, and rickettsial disease. They were significantly less likely to be diagnosed with leprosy (OR 0.03), chronic hepatitis (OR 0.04), tuberculosis (OR 0.05), schistosomiasis (OR 0.3), and helminthic infection (OR 0.3). In addition, travelers were more likely to present within 1 month of entry into Australia (OR 96), and have fever (OR 8), skin (OR 6), gastrointestinal (OR 5), or neurological symptoms (OR 5) but were less likely to be asymptomatic (OR 0.1) or have anaemia (OR 0.4) or eosinophilia (OR 0.3). Diseases in travelers were more likely to have been acquired via a vector (OR 13) or food and water (OR 4), and less likely to have been acquired via the respiratory (OR 0.2) or skin (OR 0.6) routes. We also found that travel destination and classification of traveler can significantly influence the likelihood of a specific diagnosis in travelers. Six percent of travelers developed a potentially vaccine-preventable disease, with failure to vaccinate occurring in 31% of these cases in the pretravel medical consultation. CONCLUSIONS: There are important differences in the spectrum of illness, clinical features, and mode of disease transmission between returned travelers and immigrants/refugees presenting to hospital-based Australian infectious diseases units with an illness acquired overseas.

Adolescent↗
PubMedDate not supplied

Scrub typhus-associated hemophagocytic syndrome.

A patient was admitted to our hospital with fever of unknown origin, lymphadenopathy and moderate anemia. The diagnosis of scrub typhus (tsutsugamushi disease) was established on specific serologic demonstration of antibodies to the cross-reacting proteins OX-K antigen and reaffirmed by successful treatment with doxycycline. The diagnosis of hemophagocytic syndrome (HPS) was made on the cytologic findings of many histiocytes containing phagocytosed blood cells in the marrow aspirate. The hemophagocytosis phenomenon disappeared after the scrub typhus was successfully treated, thus suggesting the relationship between scrub typhus and hemophagocytosis. In a patient with rickettsial diseases including scrub typhus, associated with HPS, it is important to understand the relationship between the two disorders since the prognosis for HPS, if untreated, is very poor.

Adult↗
PubMed2005

Tick-borne encephalopathies : epidemiology, diagnosis, treatment and prevention.

Tick-borne encephalopathies constitute a broad range of infectious diseases affecting the brain and other parts of the CNS. The causative agents are both viral and bacterial. This review focuses on the current most important tick-borne human diseases: tick-borne encephalitis (TBE; including Powassan encephalitis) and Lyme borreliosis. Rocky Mountain spotted fever (RMSF) and Colorado tick fever (CTF), less common tick-borne diseases associated with encephalopathy, are also discussed. TBE is the most important flaviviral infection of the CNS in Europe and Russia, with 10 000-12 000 people diagnosed annually. The lethality of TBE in Europe is 0.5% and a post-encephalitic syndrome is seen in over 40% of affected patients, often producing a pronounced impairment in quality of life. There is no specific treatment for TBE. Two vaccines are available to prevent infection. Although these have a good protection rate and good efficacy, there are few data on long-term immunity. Lyme borreliosis is the most prevalent tick-borne disease in Europe and North America, with >50 000 cases annually. Localised early disease can be treated with oral phenoxymethylpenicillin (penicillin V), doxycycline or amoxicillin. The later manifestations of meningitis, arthritis or acrodermatitis can be treated with oral doxycycline, oral amoxicillin or intravenous ceftriaxone; intravenous benzylpenicillin (penicillin G) or cefotaxime can be used as alternatives. The current use of vaccines against Lyme borreliosis in North America is under discussion, as the LYMErix vaccine has been withdrawn from the market because of possible adverse effects, for example, arthritis. RMSF and CTF appear only in North America. RMSF is an important rickettsial disease and is effectively treated with doxycycline. There is no treatment or preventative measure available for CTF.

Animals↗
PubMed2006

Far eastern tick-borne rickettsiosis: identification of two new cases and tick vector.

We recently reported the first documented cases of a new rickettsial disease caused by Rickettsia heilongjiangensis in the Russian Far East (Far Eastern tick-borne rickettsiosis). Here we report the amplification of DNA of R. heilongjiangensis from both the skin biopsy of an acutely ill patient and the tick removed from him prior to the disease development. The tick has been identified as Haemaphysalis spp. The clinical picture was that of a spotted fever group rickettsiosis and a seroconversion was noted with R. heilongjiangensis antigen. Screening testing of both species of Haemaphysalis ticks inhabiting Russian Far Eastern regions showed that up to 28.13% of H. concinnae and 4.48% of H. japonica douglasii ticks harbor R. heilongjiangensis. It has been concluded that H. concinnae may serve as the main vector for the transmission of R. heilongjiangensis. H. japonica douglasii ticks harbor several varieties of rickettsiae. DNA of "Candidatus Rickettsia tarasevichiae," previously found in Ixodes persulcatus ticks, was amplified from one male tick. Two sequenced complete gltA genes belong to the novel spotted fever group rickettsial species provisionally called here "Candidatus Rickettsia principis" variants Hjd54 and Hjd61. The rate of infection has been found to be not higher than 1.5%.

Adult↗
PubMed2002

Mechanisms of immunity against rickettsiae. New perspectives and opportunities offered by unusual intracellular parasites.

Investigation of the biology, pathology and immunology of rickettsial diseases offers new insights useful not only for the field of rickettsiology, but more importantly for the understanding of general principles of host-intracellular parasite relationships and, in particular, the immune interaction between endothelial cells and immune cells in the context of infection.

Animals↗
PubMed1977

Papilledema in endemic typhus.

A 21-year-old women developed severe bilateral papilledema during an acute febrile disease. Her optic disk margins were blurred and the disks were elevated up to 5 diopters. Splinter hemorrhages, cotton-wool exudates, cytoid bodies, and sheathing of veins were also present. The pyrexia was caused by murine typhus diagnosed by serologic tests. These tests revealed that Proteus OX-19 agglutination titer rose to 1:12800, and a positive complement fixation test titer was 1:640 with Rickettsia mooseri antigens. Neurological examination results, skull roentgenograms, brain scan, electroencephalogram, and the cerebrospinal fluid were all within normal range, thereby excluding intracranial hypertension. After the patient's recovery from the rickettsial disease, the papilledema abated gradually until her fundi reverted to normal.

Adult↗
PubMed1990

Biological characterization of major polypeptides on the surface of spotted fever group rickettsiae.

There are two major polypeptides on the surface of spotted fever group rickettsiae that play important roles as immunogens and possibly relate to the pathogenicity of rickettsial diseases. Digestion with trypsin and staphylococcal V-8 protease shows that the 115-kDa protein of Rickettsia conorii is a trypsin-sensitive, surface-exposed protein. The 135-kDa protein is relatively trypsin resistant. Both proteins resist heat treatment up to 52 degrees C and maintain their antigenic reactivity with monoclonal antibodies when the intact rickettsiae are heated. When rickettsiae are dissolved in SDS-containing sample buffer, these polypeptides lose their antigenic reactivity with monoclonal antibodies after incubation at 45 degrees C for 10 min. Staphylococcal V-8 protease does not appear to affect these polypeptides under the current experimental conditions. Monoclonal antibody to the 115-kDa protein reduces rickettsial attachment. The 115-kDa polypeptide may play a role in rickettsial adhesion to the host cell surface.

Bacterial Adhesion↗
PubMed1993

Pathologic study of mice infected with Rickettsia tsutsugamushi R19 strain.

Scrub typhus, an acute febrile infectious disease caused by R. tsutsugamushi, has been reported from various parts of the far east and pacific rim of Asia including Korea. It is well known that all human pathogenic rickettsia share an affinity to endothelial cells of the small blood vessels and evoke vascular inflammation variably associated with a rash, microthrombi, and hemorrhage. We infected the ICR mice by inoculating sublethal doses of R. tsutsugamushi R19 strain intraperitoneally and observed the pathologic changes by time sequence. The histopathologic features of experimentally induced scrub typhus in the mice were generally nonspecific interstitial inflammations characterized by interstitial pneumonitis, periportal inflammation, multifocal hepatic necrosis, interstitial nephritis, sinusoidal engorgement, and lymphohistiocytic cell infiltration in lymph nodes and spleen. Contrary to the general features of other rickettsial diseases, the pathologic process of scrub typhus experimentally induced by R. tsutsugamushi R19 strain mainly involved the interstitial connective tissue but not the blood vessels.

Animals↗
PubMed2003

Evaluation of an immunoglobulin M capture enzyme-linked immunosorbent assay for diagnosis of Orientia tsutsugamushi infection.

To differentiate scrub typhus from other acute febrile diseases, a rapid and reliable serological diagnosis is important. We developed an immunoglobulin M (IgM) capture enzyme-linked immunosorbent assay (ELISA) for diagnosis of recent Orientia tsutsugamushi infections in humans. The 56-kDa major outer membrane protein of O. tsutsugamushi is well known as the most immunodominant antigen in scrub typhus. The test is based on the use of the biotinylated recombinant 56-kDa protein of O. tsutsugamushi Boryong, Bor56, which was expressed as a fusion protein with a maltose-binding protein in Escherichia coli. In the test, the serum IgM antibodies were captured by anti-human IgM antibodies coated onto a microtiter plate. The captured IgM antibodies were revealed through sequential addition of biotinylated Bor56 antigen and peroxidase-conjugated streptavidin to the plate. The IgM capture ELISA was compared with the immunofluorescence antibody assay (IFA) by testing 176 serum samples from patients with diagnosed cases of rickettsial disease and patients with other acute febrile diseases. Of the 81 IgG IFA-positive samples, 78 tested positive (sensitivity, 96.3%) and all 31 IgM IFA-positive samples tested positive (sensitivity, 100%) by the IgM capture ELISA. The specificity of the IgM capture ELISA was 99%, and 1 of the 95 IFA-negative samples was positive in the assay. These results strongly suggest that IgM capture ELISA using the recombinant Bor56 antigen is a reliable and detailed method for the detection of early O. tsutsugamushi infection.

Antibodies, Bacterial↗
PubMed2001

OspA, a lipoprotein antigen of the obligate intracellular bacterial pathogen Piscirickettsia salmonis.

No effective recombinant vaccines are currently available for any rickettsial diseases. In this regard the first non-ribosomal DNA sequences from the obligate intracellular pathogen Piscirickettsia salmonis are presented. Genomic DNA isolated from Percoll density gradient purified P. salmonis, was used to construct an expression library in lambda ZAP II. In the absence of preexisting DNA sequence, rabbit polyclonal antiserum raised against P. salmonis, with a bias toward P. salmonis surface antigens, was used to identify immunoreactive clones. Catabolite repression of the lac promoter was required to obtain a stable clone of a 4,983 bp insert in Escherichia coli due to insert toxicity exerted by the accompanying radA open reading frame (ORF). DNA sequence analysis of the insert revealed 1 partial and 4 intact predicted ORF's. A 486 bp ORF, ospA, encoded a 17 kDa antigenic outer surface protein (OspA) with 62% amino acid sequence homology to the genus common 17 kDa outer membrane lipoprotein of Rickettsia prowazekii, previously thought confined to members of the genus Rickettsia. Palmitate incorporation demonstrated that OspA is posttranslationally lipidated in E. coli, albeit poorly expressed as a lipoprotein even after replacement of the signal sequence with the signal sequence from lpp (Braun lipoprotein) or the rickettsial 17 kDa homologue. To enhance expression, ospA was optimized for codon usage in E. coli by PCR synthesis. Expression of ospA was ultimately improved (approximately 13% of total protein) with a truncated variant lacking a signal sequence. High level expression (approximately 42% tot. prot.) was attained as an N-terminal fusion protein with the fusion product recovered as inclusion bodies in E. coli BL21. Expression of OspA in P. salmonis was confirmed by immunoblot analysis using polyclonal antibodies generated against a synthetic peptide of OspA (110-129) and a strong antibody response against OspA was detected in convalescent sera from coho salmon (Oncorhynchus kisutch).

Amino Acid Sequence↗
PubMed2006

Antibodies to Rickettsia rickettsii, Rickettsia typhi, Coxiella burnetii, Bartonella henselae, Bartonella quintana, and Ehrlichia chaffeensis among healthy population in Minas Gerais, Brazil.

Rickettsial diseases except those belonging to spotted fever group rickettsioses are poorly studied in South America particularly in Brazil where few epidemiological reports have been published. We describe a serosurvey for Rickettsia rickettsii, R. typhi, Coxiella burnetii, Bartonella henselae, B. quintana, and Ehrlichia chaffeensis in 437 healthy people from a Brazilian rural community. The serum samples were tested by indirected micro-immunoflourescence technique and a cutoff titer of 1:64 was used. The seroprevalence rates for R. rickettsii, R. typhi, C. burnetii, B. henselae, B. quintana, and E. chaffeensis were respectively 1.6% (7 samples); 1.1% (5 samples); 3.9% (17 samples); 13.7% (60 samples); 12.8% (56 samples), and 10.5% (46 samples). Frequent multiple/cross-reactivity was observed in this study. Age over 40 years old, urban profession, and rural residence were significantly associated with some but not all infections rate. Low seropositivity rates for R. rickettsii, R. typhi, and C. burnetii contrasted with higher rates of seropositivity for B. quintana, B. henselae, and E. chaffeensis. These results show that all tested rickettsial species or antigenically closely related possible exist in this particular region.

Adolescent↗
PubMed1989

Approaches to the molecular epidemiology of rickettsioses.

This review deals with the developments of molecular approaches to the investigation of rickettsial disease epidemiology. The data presented include changes in the incidence and geographic distribution of endemic rickettsioses. Use of the DNA restriction enzyme technique, in combination with DNA probe analysis, for the molecular genetic differentiation of tick spotted fever--and typhus fever--group rickettsiae and correlation between with the analysis of polypeptide composition of the above group of rickettsiae are discussed. The data are presented on progress in the identification of various Coxiella burnetii strains as a result of restriction analysis of plasmid DNA as well as chromosomal DNA in combination with DNA probe. New and detailed characteristics of classified and newly isolated strains of rickettsiae and Coxiella burnetii revealed by molecular genetic differentiation techniques are discussed. New identification techniques using DNA probes in combination with restriction analysis of chromosomal from rickettsiae and both plasmid and chromosomal DNA from Coxiella burnetii are considered to have good prospects for future use in epidemiological assessment. The establishment of reference file banks containing restriction endonuclease data on the available typical and atypical strains of rickettsiae and Coxiella burnetii is suggested.

Animals↗
PubMed1989

Diagnosis of rickettsial infections in Swedish patients: detection of specific IgM.

Since April 1986, microimmunofluorescence assays have been employed at the Department of Virology at the National Bacteriological Laboratory in Sweden to investigate the presence of specific IgM and IgG antibodies to C. burnetii and R. conorii in patient sera. A total of 111 patients with suspected rickettsial disease were investigated during the time period April 1986-November 1988. In 23 patients specific IgM was detected--in 9 to C. burnetii and in 14 to R. conorii. In thirteen of the IgM-positive patients a significant rise in specific IgG between acute and convalescent sera was also seen. All 23 patients had been travelling abroad prior to onset of disease. The microimmunofluorescence test was a simple and reliable tool in the detection of specific IgM for a rapid and accurate diagnosis of C. burnetii-and R. conorii-infections early in the course of disease.

Adult↗
PubMed1989

Q-fever and autoimmunity.

STUDY OBJECTIVE: To determine the incidence and the clinical significance of two autoimmune markers in Q-fever (smooth muscle antibodies, cold agglutinins). DESIGN: Six index cases with auto-immune disorders. Assays of 104 sera from patients with Q-fever (including index cases) using immunofluorescence for smooth muscle antibodies, microagglutination for cold agglutinins. SETTING: French National Reference Center for Rickettsial Diseases. CASES: 6 patients were studied with acute Q-fever and auto-immune disorders. 3 of whom had presented a resistance to a therapy with antibiotics. Stored samples from other patients with acute or chronic stage were also screened to appreciate the incidence of the two markers. MEASUREMENTS AND MAIN RESULTS CASE REPORTS: No correlation between Q-fever and smooth muscle antibodies titers and kinetics were found. A spurt of corticosteroids was necessary to obtain apyrexia for the patients who had presented multiple auto-immune disorders and a resistance to the classical therapy. INCIDENCE; Smooth muscle antibodies were detected in 27%, cold agglutinins in one case. They were present in 23% of the patients with acute cases and in 38% with chronic stage. CONCLUSION: The incidence of auto-immune disorders is unexpectedly high and could explain some manifestations of acute Q-fever e.g the resistance to therapy with antibiotics which are not yet clear. Then the association during the acute stage of auto-immune disorders with the persistence of clinical or biological findings after three weeks therapy could recommend the use of corticosteroids.

Adult↗