[BRILL-ZINSER DISEASE AS A CONSEQUENCE OF RICKETTSIA PROWAZEKII PERSISTENCE IN PREVIOUSLY ILL WHO HAVE HAD EPIDEMIC TYPHUS (EPIDEMIOLOGIC ASPECTS)].

Materials, that summarize data of original research and scientific literature on epidemiology and problems of persistence during epidemic typhus, whose causative agent (Rickettsia prowazekii) is reactivated in the organism of the previously ill and is manifested as Brill-Zinser disease, are presented. A retrospective analysis was carried out with the data obtained by Russian (All-Union) Centre for Rickettsioses during study of epidemiologic examination maps of 5705 typhus nidi and results of 19 463 blood sera analysis during study of immunologic structure of population in the territories of the former USSR for the period from 1970 to 1992. A decrease of epidemic typhus morbidity and an increase of the fraction of Brill-Zinser disease took place as a result of pediculosis corporis control. In separate territories specific weight of Brill-Zinser disease was 48% in 1952, up to 80% in 1969, and from 1977 all the ill were previously ill. However, during the perestroika period and afterwards, due to a reduction of economic and hygienic living conditions, appearance of refugees, the immune structure regarding typhus began to change. Due to the buildup of the population migration process and the presence of risk groups (refugees, homeless) among population of regions, where local wars are waged, the enhancement of methods of epidemic typhus and Brill-Zinser disease diagnostics and pediculosis corporis eradication is necessary. Study of R. prowazekii by molecular-genetics methods is necessary for complete understanding of its mechanism of persistence.

[Emergence of tick-borne spotted fever group rickettsiosis in Moscow].

AIM: Analysis of clinical cases of tick-borne spotted fever (TSF) group rickettsiosis in 2005 - 2010. MATERIALS AND METHODS: General clinical, biochemical and serological parameters were determined in 10 tick-borne spotted fever group rickettsiosis patients who had visited various geographical regions of the World. RESULTS: TSF group rickettsiosis diagnostic criteria, optimal serological diagnostics timing were determined. Possible diagnostic errors, features of serological diagnostics and antibacterial therapy of this nosologic form are discussed. CONCLUSION: Indication for TSF examination are primarily epidemiologic including tick attachment indication and clinical data. Serological studies are positive only in 3 - 4 weeks after the onset of the infection and thus can not be used for early diagnostics.

[Ecology of Rickettsia and epidemiology of rickettsioses].

Questions of ecology of obligate-transmissible rickettsioses causative agents and their natural environment--organism of blood-sucking arthropoda (ixodes, gamasid ticks, harvest ticks, lices, fleas) are considered. In tick organism Rickettsia are propagated, and transphase and transovarial transmission of rickettsia maintains population in natural focuses. The relationship between Rickettsia ecology and rickettsioses epidemiology is evident. Data about new-revealed and recurrent rickettsioses and role of molecular-biological and genetical methods of Rickettsia detection are represented. Biological and social factors having influence on appearance of new and recurrent rickettsioses are determined with the aim of their prediction.

Comparison of genomes of Coxiella burnetii strains using formal order analysis.

The Coxiella burnetii strain NL3262 was isolated during the Q fever outbreak in the Netherlands in 2007-2010. Formal-order analysis (FOA) was used to study the similarity of the genome (chromosome and plasmid) of this strain with the genomes from other strains. Chromosomes from ten C. burnetii strains and eight plasmids were studied with FOA tools such as 'Map of genes' and 'Matrix of similarity.' The 'Map of genes' tool showed that the chromosome of strain C. burnetii str. NL3262 distanced itself by the index of average remoteness (g) of 1.449640 (x-axis) from chromosomes of other strains (g 1.448295-1.448865). The 'Matrix of similarity' was used for an advanced analysis of the obtained results. The complete similarity of the components of chromosomes and plasmids was determined by pairwise comparison and the identification of nucleotides matching with them. A total of 84.90% of the chromosomal components of C. burnetii strain NL3262 coincided completely with the chromosomal components of strain Z3055. For chromosomes of other strains, this percentage varied from 12.06% to 47.14%. The plasmid of strain NL3262 had 50.0% of the components being completely coincident with the components of the plasmid of RSA 331; with RSA 493 it was 29.89%. Thus, C. burnetii str. NL3262 is the closest to str. Z3055 by the similarity of the chromosomal components, but on the index of average remoteness of the chromosome and the similarity of the plasmids' QpH1 components, it is the closest to strain RSA 331.

[Bartonella infection in hematological practice].

AIM: To characterize the clinical and histological features of Bartonella infection in patients asking for hematological advice and to assess the significance of serological and molecular methods for the diagnosis of this infection. MATERIALS AND METHODS: The case histories of 747 patients asking for advice at the Hematology Research Cancer, Russian Academy of Medical Sciences, for lymphadenopaphy were retrospectively studied. The study included 10 patients in whom Bartonella infection could be suspected. For verification of the diagnosis, the authors conducted a serological study of the patients' sera and a molecular study of archival paraffined lymph node biopsy specimens. RESULTS: The study showed it possible to make a retrospective diagnosis of cat-scratch disease (CSD) by polymerase chain reaction (PCR) used in the study of archival lymph node biopsy specimens and stained preparations. CONCLUSION: CSD should be suspected when a patient has sustained lymphadenopathy and a respective epidemiological history (feline contact). Bartonella infection should be diagnosed on the basis of a dynamic serological study and, if possible, PCR of cells from biopsy specimens of lymph nodes or the lesion developed at the site of Bartonella penetration into the human body (primary affect).

Rickettsiologist Pavel F. Zdrodovskii: larger than life, and not just for his famous book.

This article highlights the biography and scientific accomplishments of Pavel F. Zdrodovskii and his contributions to understanding the biology, pathogenesis, treatment, prevention and epidemiology of brucellosis, rickettsioses and many other infectious diseases.

[Epidemiological aspects of the present-day demographic situation in Russia].

Study of reference rate in healthcare institutions in 1991 - 2001 demonstrated a steady growth of general mortality and disease incidence among the population (by 22.7% and 8.1%, respectively). The number of patients with acute and chronic diseases registered in 2001 was by 16.4% higher than that in 1991. These trends were characteristic of all disease classes, but the most intensive growth was observed in such classes as diseases of blood and hemopoetic organs (2.5 times), endocrinal and urogenital diseases (1.8 times). Disease incidence and general mortality among children aged 0 to 14 had grown by 25% and 33.2%, among adolescents--by 60% and 71.1%, among adults--by 5.2% and 20.3%, respectively. These negative trends in population health were accompanied by a constant growth of incapacitation rate in 1990 - 2000 (2.4 times, and 4.3 times among children and adolescents younger than 18). There is a correlation between mortality and traditionally used demographic parameters, which suggests that mortality should be recognized the key demographic parameter. In order to achieve a satisfactory level of population health and adequate demographic transition, and to develop general sanatory strategy, the State should undertake powerful, goal-seeking, society-oriented measures, including deep clinical and epidemiological study of human pathology.

[Evaluation of the epidemiological situation in different territories of the Russian Federation, based on the Bank of Standard Blood Sera].

The Bank of Standard Sera created in the Gamaleya Research Institute of Epidemiology and Microbiology provide for evaluation the epidemiological situation in any separate territory and in the whole of the country. The collection of certified blood sera is divided according to different territories of the country and makes it possible to obtain the retrospective and operative information on the level of population immunity and the immune structure of the population with respect to different infective agents, and to reveal the susceptible group of the population. The analysis of the unfavorable character of the epidemiological situation in the inspected territory with due consideration of its climato-geographical and anthropogenic environmental, socio-demographic characteristics, the level of population immunity and the immune structure of the population with respect to different infective agents makes it possible to carry out the epidemiological diagnostic (an outbreak, the import of infection, the use of a bacteriological weapon), prognosis and the prophylaxis of diseases, as well as the epidemiological cartography of territory.

[Survival of Coxiella burnetii in soil].

For the first time the survival of Coxiella burnetii of five types in soils has been studied. The survival of C. burnetii has been found to depend on the content of organic substances in black earth, as well as soil temperature. The method for the prevention of an epidemic outbreak of Q fever directly under the natural conditions has been proposed.

[Bartonella and bartonellosis--emerging and re-emerging infections: epidemiology, clinical course, diagnosis].

Information on the epidemiology, clinic and diagnostics of bartonellosis is updated. The importance of bartonellosis lies in the fact that its main risk group embraces patients with immunodeficiencies of different origin, the number of such patients constantly growing. The diagnostics of bartonellosis is insufficiently developed and the research on Bartonella organisms, except for the trunch (Volynia) fever causative agent, is insufficient in our country.

Problems and perspectives of molecular epidemiology of infectious diseases.

Current tendencies and problems of molecular biology and its application in infectious diseases are discussed. Basic stages of the development of molecular epidemiology as a leading tool for epidemiological studies are reviewed. More than 30 years ago, molecular epidemiology was first used to study nosocomial infections. Special attention is given to the achievements of Russian scientists, especially in the discovery of Astrakhan spotted fever Rickettsia, noncultured forms of Vibrio cholerae, and the microorganism "Montezuma." Also, the development of PCR-based methods of identification and typing of Mycobacterium tuberculosis by Russian specialists and its significant role in strategies for diagnosing and treatment of tuberculosis are discussed. Now, the most important field of application of molecular biology methods is bacterial evolution, especially with regard to pathogenic microorganisms and emerging infections. Searching for the novel pathogenic agents, establishment of the infectious nature of diseases with unclear origin, and determining the precise mechanisms of pathogenicity are most intriguing issues. So, molecular biology should play a major role both in clinical and research fields.

Astrakhan fever rickettsiae: antigenic and genotypic analysis of isolates obtained from human and Rhipicephalus pumilio ticks.

Two spotted fever group rickettsia strains, A-108 and A-167, were isolated from the hemolymph of Rhipicephalus pumilio ticks collected in the Astrakhan region of Russia, which is area endemic for Astrakhan fever. These tick isolates were compared with a strain isolated from a patient suffering from Astrakhan fever and with reference spotted fever group rickettsiae strains. New tick isolates and the human strain were identical in their serologic, antigenic, and genetic characteristics by several methods: microimmunofluorescence, protein gel electrophoresis with immunoblotting, polymerase chain reaction followed by restriction endonuclease fragment length polymorphism analysis, and pulsed-field gel electrophoresis (PFGE). Astrakhan fever rickettsiae were found to be serologically and antigenically similar to Israeli spotted fever rickettsiae. Both of them probably belong to a single Rickettsia conorii pathotype complex. Only PFGE pattern analysis could clearly discriminate Astrakhan fever rickettsiae from other isolates.

New species of Neotrombicula (Acari: Trombiculidae) from the southern Primorye territory, Russian Far East.

Neotrombicula kanekoi n. sp. is described from Apodemus agrarius and Crocidura lasiura collected in the Primorye Territory, Russian Far East. This species is close to N. subsignata but differs in having eight setae in the first posthumeral row, whereas N. subsignata has six. The new species is the sixth known member of the bisignata group in the Far East.

Experimental double infection with Coxiella burnetii and tick-borne encephalitis virus in Dermacentor reticulatus ticks.

Experimental parenteral inoculation of Dermacentor reticulatus ticks with the rickettsia Coxiella burnetii (C.b.) and tick-borne encephalitis (TBE) virus resulted in a generalized rickettsial and viral infection, irrespective of whether the agents were given simultaneously or by a 7 days interval apart. Both agents multiplied intensively in ticks, C.b. being detectable predominantly in cytoplasmic vacuoles and TBE virus mostly in the endoplasmic reticulum.

Mixed Rickettsia-virus infection in Dermacentor reticulatus imago.

Electron microscopic examination revealed replication and accumulation of Rickettsia sibirica in the fat body of experimentally infected Dermacentor reticulatus ticks. Rickettsia are released from the fat body cells by budding being surrounded with cytoplasm and plasmalemma of the host cell. Eukaryotic cell structures have been detected consisting of lamella layers whirled around the intact rickettsiae. In addition to rickettsia, microorganisms morphologically resembling Francisella tularensis and an orbivirus were found in tick tissues at morphological examination. The morphology of the virus and stages of its morphogenesis are described. Mixed viral and rickettsial infection has been shown to develop in the same ticks and even in the same fat body cells in a very close association.

Ultrastructure of Rickettsia sibirica during interaction with the host cell.

Rickettsia sibirica (strain Netsvetaev) was found within large translucent spaces in the cytoplasm of L-929 cell monolayer cultures on day 6 postinfection (p.i.). These rickettsiae were rod shaped 0.3 X 10 microns in size encircled by a halo of up to 200 nm wide corresponding to a capsule-like coat. Directly on the cell wall was a 12 nm thick microcapsule in which subunit structures with 12 nm thick spacing could be recognized. The cell wall membrane was 14 nm thick with a wider internal layer occasionally in a section found split into two electron-dense lamels; the internal layer corresponded to peptidoglycan. The periplasmic space with an average thickness of 5 nm separated the cell wall from a 7 nm thick cytoplasmic membrane. The ultrastructure of R. sibirica was similar to that of other rickettsiae, although the capsule-like coat was thicker than in spotted fever (SF) group rickettsiae.

[New and emerging rickettsial and bartonella infections]. / Novye i vozvrashchaiushchiesia rikketsiozy i bartonellezy.

There have been recently reports on over 10 new and resurgent rickettsioses and bartonelloses in different countries, which reflects both socioeconomic processes in society and a higher methodological level of indication and identification of causative agents. In 1991, the author' laboratory, N. F. Gamaleya Research Institute of Experimental Medicine, Russian Academy of Medical Sciences, established the etiology of the new rickettsiosis Astrakhan spotted fever. It separated and studied 2 strains of Rickettsia sp. nov. from patients and 8 ones from the carrier the Ixodes tick Rhipicephalus pumilio. It is suggested that the natural focus has transformed to the anthropurgic one due to technogenic environmental pollution. The annual increase in morbidity rates (2000 cases in 1983 to 2000) and its area are a challenge to public health care and medical science. The paper presents data on the new bartonellosis cat-scratch disease (caused by Bartonella henselae) detected not only in Russia. There is also information on tick-borne rickettsiosis, epidemic typhus, and trench fever as resurgent infections.

[Determination of Ehrlichia genome size by pulse gel electrophoresis]. / Opredelenie razmera genoma patogennykh érlikhii metodom pul's-gel'-élektroforeza.

Ehrlichia infections are more and more common in the USA and Europe. The genetics and genome organization of Ehrlichia are little studied due to great difficulties in cultivating these bacteria. Pulse gel electrophoresis was first used to determine the sizes of a genome of 3 representatives of the genus Ehrlichia. The sizes of a genome was established for E. sennetsu (881 kb), for E. risticii (867 kb), E. chaffeensis (1,236 kb).

[Distribution of biological particles in two-phase systems of water soluble polymers and salts]. / Raspedelenie biologicheskikh chastits v dvukhfaznykh sistemakh vodorastvorimykh polimerov i solei.

The paper discusses the problems of purification of Provachek's rickettsias used to prepare typhus vaccines and diagnostic kits. The currently available agents contain many admixtures of rickettsias products, more commonly yolk and chick embryo yolk sack cell detritus, which make it impossible to determine the true antigenic properties of rickettsias in the context of protection and diagnosis. By applying the well-known principle of distribution of biological particles in the two-phase systems of water soluble polymers, investigations were made to examine the distribution of rickettsias and their infected biological mass in the system: polyethylene glycol-6600, sodium-500 dextran sulfate, potassium phosphate, sodium chloride in order to prepare agents of pure rickettsias. It has been found that rickettsias are distributed in the polymer-enriched phase, their number and the degree of purity when isolated from the infected biological mass depends on the capacity of an interphase wherein tissue detritus sorption occurs.

[Immunobiological properties of phospholipid antigens of Rickettsia prowazekii incorporated into rickettsial liposomal preparations]. / Izuchenie immunobiologicheskikh svoistv fosfolipidnykh antigenov Rickettsia prowazekii v sostave rickettsial liposomal preparations.

In this article materials on obtaining rickettsial liposomal preparations on the basis of R.prowazekii phospholipid antigen and chemical typhus vaccine are presented. Electron microscopic studies revealed the formation of liposomes in this system. Liposomal preparations were not hemotoxic and produced no toxic action in experiments on guinea pigs and white mice. Phospholipid antigens incorporated into liposomal preparations were found to produce a potentiating effect on the immunogenic properties of chemical typhus vaccine. The adjuvant properties of rickettsial phospholipids incorporated into liposomes on the basis chemical typhus vaccine were registered.