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Ecological questions concerning rickettsiae.

The past ten years were characterized by the appearance of several "new" transmissible spotted fever group (SFG) rickettsioses, e.g. Israeli, Japanese and Astrakhan fevers. The factors responsible for their establishment probably include the introduction of chemicals from industry, agriculture and the timber industry into natural habitats. Such factors may influence the pathogenicity of these rickettsiae. In this case, in addition to the human influence, the mechanism of the circulation of the agents under natural conditions of both abiotic (climate, etc.) and biotic (flora and fauna) components may play a decisive role. The modern management of breeding domestic animals, indoor and outdoor maintenance, seasonal migrations, new animal foods, stress, etc., can be important factors affecting the biological properties of the Q fever agent. Nonpathogenic rickettsiae, rickettsia-like symbionts and other microorganisms circulating in nature may also influence the pathogenic rickettsiae. Studies on their interrelationships in hosts and vectors may markedly contribute to the understanding of the circulation of pathogenic rickettsiae in nature. Recognition of factors causing the appearance of new rickettsial agents or differences in pathogenicity of rickettsial strains is important not only for the prognosis of rickettsial diseases but also for the prognosis of other infectious diseases.

Animals↗

Murine typhus and spotted fever in Israel in the seventies.

One hundred and eleven cases of rickettsial disease-100 cases of murine typhus and 11 cases spotted fever--seen over a four year period at the Chaim Sheba Medical Center are reviewed. The clinical picture of murine typhus (caused by Rickettsia mooseri and transmitted by Xenopsylla cheopis) could not be distinguished from that of spotted fever (caused by a Rickettsia similar to Rickettsia conori and transmitted by Rhipicephalus). Some quite severe cases of murine typhus and some relatively mild cases of spotted fever were seen.

Adolescent↗

Serologic evidence for human ehrlichiosis in Africa.

Human ehrlichiosis is a recently recognized rickettsial disease. It is caused by Ehrlichia chaffeensis, an intraleucocytic Gram-negative, obligate intracellular bacterium, grouped within the genus Ehrlichiae. Most human cases of ehrlichiosis have been diagnosed in the USA. Two cases have been reported outside of the USA, one in Europe and one in Africa. From 1 January to 30 June 1992, 765 sera from blood donors or other asymptomatic subjects in 8 African countries, including Ivory Coast, Burkina Faso, Mali, Central African Republic, Angola, Zimbabwe, Mozambique and Commores Islands, were tested by indirect immunofluorescence for the presence of E. chaffeensis antibodies. Positive sera were confirmed by Western immunoblotting. Only two of 765 sera tested were positive. One serum obtained from Burkina Faso had an IgG titer of 1:200 and one from Mozambique had an IgG titer of 1:80. Human ehrlichiosis seems to occur infrequently in Africa, although many more sera from additional African countries need to be evaluated.

Africa↗

Rickettsial infection in marine crustacea.

A rickettsial disease is described in the crab Carcinus mediterraneous Czerniavski. The pathogen develops within vacuoles in connective tissue cells. 2 morphologically different forms are observed in the last stage of infection. The systematic position of this procaryote is discussed.

Animals↗

Platelet aggregation and stimulation of leucocyte procoagulant activity by rickettsial lipopolysaccharides in rabbits and in man.

The effects in vitro of 4 purified lipopolysaccharide (LPS) preparations from Rickettsiae on platelets and leucocytes were studied in rabbits and in man. All LPS induced aggregation in rabbit platelet-rich plasma but to differing degrees. This activity was abolished by inactivation of complement. None of the preparations induced aggregation of human platelets. Both rabbit and human leucocytes, when incubated with each of the rickettsial LPS preparations, generated a potent procoagulant activity (tissue factor). These findings add further support to the concept that rickettsial LPS behave as typical LPS from gram-negative bacteria and may be relevant to the understanding of the mechanism(s) responsible for triggering intravascular coagulation in rickettsial diseases.

Animals↗

Tick-borne fever: a review.

The literature on tick-borne fever is reviewed. Tick-borne fever is a rickettsial disease of sheep and cattle characterised by high fever and severe leucopaenia. The causative agent, Cytoecetes phagocytophila invades the neutrophils and monocytes and is transmitted by the tick Ixodes ricinus. There is very little information on the pathogenesis and immunogenesis of the disease but there is ample evidence that infected animals are predisposed to other diseases. Animals infected with tick-borne fever resist reinfection for a variable period of time. The organisms may persist in the blood of recovered animals for up to two years. Humoral antibodies are produced two weeks after infection and continue to be detected for many months but their significance on protective immunity is not clearly established.

Animals↗

Heartwater in Ghana: implications for control of ticks.

Heartwater, an often fatal rickettsial disease of domestic ruminants transmitted by Amblyomma variegatum ticks, ranks with the A. variegatum-associated skin disease dermatophilosis as a major constraint to the upgrading of livestock productivity in Ghana. An epidemiological survey, using new diagnostic tests, is being carried out to determine the incidence and distribution of heartwater and other tickborne diseases in Ghanaian cattle, sheep and goats. Preliminary results from a longitudinal survey being carried out at sites in the Greater Accra Region indicating that although the vector ticks and the disease agent are widespread outside urban areas, not all animals are being exposed to heartwater during the first few months of life when an inverse age related resistance allows development of immunity without clinical disease. Thus a susceptible sub-population, at risk from heartwater, can exist even in areas of high tick challenge. The significance of these results for present and future tick and disease control strategies is discussed.

Animals↗

Murine typhus presenting as subacute meningoencephalitis.

Murine typhus is a febrile systemic illness, presenting with headache and undulating fever. Neurological involvement is considered a rare complication. During 1994 and 1995, 34 patients admitted to our hospital were diagnosed as having murine typhus. Five of these patients presented with a syndrome of subacute "aseptic" meningitis or meningoencephalitis. Three had bilateral papilloedema and 2 had focal neurological signs. None had a rash or other systemic findings suggestive of rickettsial disease. The diagnosis was based on serum and cerebrospinal fluid serology and on prompt response to doxycycline therapy. These cases suggest that neurological involvement in murine typhus is more common than previously suspected and that murine typhus should be included in the differential diagnosis of subacute meningitis in endemic areas.

Acute Disease↗

Clinical and laboratory findings of boutonneuse fever in Sicilian children.

UNLABELLED: The spectrum of signs and symptoms of 645 consecutive children diagnosed from 1984 to 1996 with boutonneuse fever (BF), a mild rickettsial disease caused by Rickettsia conorii endemic in the Mediterranean basin, are reported. The major clinical features were fever (97.2%), exanthema (96.1%) and "tache noire" (71.8%). The large series examined permitted the authors to observe some rare or disregarded clinical features of the disease: cases with papulovesicular exanthema, reported previously only in adults who had been infected by R. conorii in Africa; and cases in which the only symptom was an isolated lymphadenopathy. CONCLUSION: R. conorii infection should be considered in patients with lymphadenopathy who live in or have travelled to an endemic area, even when other, more specific features, are not present. Also pox-like vesicular lesions may be caused by this organism, awaiting confirmation by using culture techniques instead of serology. The serological confirmation of BF by immuno fluorescent antibody test is possible only late in the illness.

Adolescent↗

Primary HIV type-1 infection misdiagnosed as Mediterranean spotted fever.

The case studies of four patients, two men and two women between the ages of 42 and 54 years, are described. They presented to a hospital emergency department during the summer months with acute fever and exanthema. These are the primary symptoms of Mediterranean spotted fever (MSF), an endemic rickettsial disease in the Mediterranean basin that is seen particularly during the summer. The patients were clinically diagnosed as having MSF, but their diagnoses were not confirmed by serological testing. One patient was diagnosed with primary human immunodeficiency virus type 1 infection (HIV-1) 10 days later. The remaining three patients were diagnosed with HIV infection years later, but it is very likely that they also had primary HIV infection when MSF was presumed. When a patient develops sudden onset of fever and a maculopapular rash that is characteristic of MSF, the possibility of primary HIV-1 infection should be considered.

Adult↗

Spotted fever group rickettsial infection in south-eastern Australia: isolation of rickettsiae.

Flinders Island spotted fever (FISF), a spotted fever group (SFG) rickettsial disease first described in 1991, occurs in south-eastern Australia. The isolation of the aetiological agent is described for the first time having been obtained from the blood of two patients. An additional 22 cases are also reported. Of these patients four had positive initial serology, and 20 showed seroconversion (using Rickettsia australis as antigen). Acute phase blood specimens taken from seven patients caused neonatal mice to seroconvert to R. australis and a blood specimen from one of these patients (and one other) yielded rickettsiae. A field survey for possible reservoir and vector animals on Flinders Island, Tasmania and in Gippsland, Victoria (both in south-eastern Australia) yielded 217 vertebrates and 1445 invertebrate ectoparasites, mostly ticks. Ixodes cornuatus from humans and dogs in Gippsland produced seroconversion to SFG rickettsia when inoculated into mice but no invertebrate pools from Flinders Island produced seroconversion in mice. Haemolymph from an individual I. cornuatus removed from a human in Gippsland, yielded a SFG rickettsia on tissue culture. Sera from several species of native vertebrates, especially the bush rat, Rattus fuscipes, were positive for antibodies to SFG rickettsia.

Adolescent↗

Hemofiltration in severe high microvascular permeability pulmonary edema secondary to rickettsial spotted fever.

Two patients, affected by spotted fever, developed low pulmonary capillary wedge pressure (PCWP) pulmonary edema with severe hypoxemia. Conventional specific and supportive therapy, including mechanical ventilation, failed to induce significant respiratory and hemodynamic improvement which was dramatically reached by means of hemofiltration. Removal of circulating middle molecular weight peptides by the convective mass transfer, characteristic of hemofiltration, offers a new and effective therapeutic approach for the adult respiratory distress syndrome secondary to rickettsial diseases.

Adult↗

Sequence analysis of the 190-kDa antigen-encoding gene of Rickettsia conorii (Malish 7 strain).

The complete nucleotide (nt) sequence of the gene (rompA) encoding the 190-kDa immunodominant surface antigen (rOmpA) of Rickettsia conorii (Malish 7 strain) was determined. Sequence analysis revealed an ORF of 6063 nt encoding a deduced protein of 203,247 Da. Ten consecutive highly conserved repeat units, located at the 5' end of rompA, spanned 2.2 kb. Two types of repeats could be identified: type I of 225 bp, and type II of 216 bp. The order and number of repeats differed from those reported for R. conorii (Kenya tick typhus strain), R. akari (Kaplan strain) and R. rickettsii (R strain). Alignment of the R. conorii (Malish 7 strain) rompA gene with its R. rickettsii homolog revealed 95% nt sequence similarity. The conservation of rompA across several pathogenic spotted fever group (SFG) rickettsial species suggests that it may be a potential candidate for use as a subunit vaccine for SFG rickettsial diseases.

Amino Acid Sequence↗

Relapse of rickettsial Mediterranean spotted fever and murine typhus after treatment with chloramphenicol.

In the years 1975-1984, 132 patients with rickettsial Mediterranean spotted fever and murine typhus were treated with chloramphenicol or tetracycline. Among the 24 patients who received chloramphenicol ten relapsed and one failed to respond at all. None of the 108 recipients of tetracycline suffered a relapse. It appears that tetracycline should serve as first-line therapy in several rickettsial diseases.

Chloramphenicol↗

An efficacious recombinant subunit vaccine against the salmonid rickettsial pathogen Piscirickettsia salmonis.

Piscirickettsia salmonis is the aetiological agent of salmonid rickettsial septicaemia, an economically devastating rickettsial disease of farmed salmonids. Infected salmonids respond poorly to antibiotic treatment and no effective vaccine is available for the control of P. salmonis. Bacterin preparations of P. salmonis were found to elicit a dose-dependent response in coho salmon (Oncorhynchus kisutch), which varied from inadequate protection to exacerbation of the disease. However, an outer surface lipoprotein of P. salmonis, OspA, recombinantly produced in Escherichia coli elicited a high level of protection in vaccinated coho salmon with a relative percent survival as high as 59% for this single antigen. In an effort to further improve the efficacy of the OspA recombinant vaccine, T cell epitopes (TCE's) from tetanus toxin and measles virus fusion protein, that are universally immunogenic in mammalian immune systems, were incorporated tandemly into an OspA fusion protein. Addition of these TCE's dramatically enhanced the efficacy of the OspA vaccine, reflected by a three-fold increase in vaccine efficacy. These results represent a highly effective monovalent recombinant subunit vaccine for a rickettsia-like pathogen, P. salmonis, and for the first time demonstrate the immunostimulatory effect of mammalian TCE's in the salmonid immune model. These results may also be particularly pertinent to salmonid aquaculture in which the various subspecies are outbred and of heterologous haplotypes.

Amino Acid Sequence↗

A subset of Cowdria ruminantium genes important for immune recognition and protection.

Cowdria ruminantium causes the tick-borne rickettsial disease of heartwater, which is devastating to livestock production in sub-Saharan Africa. Current diagnosis and control methods are inadequate. We have identified and sequenced a subset of genes encoding recombinant antigens recognized by antibody and peripheral blood mononuclear cells from immune ruminants. The identified genes include many with significant similarity to those of Rickettsia prowazekii, genes predicted to encode different outer membrane proteins and lipoproteins and a gene containing an unusual tandem repeat structure. Evidence is presented for immune protection by recombinant antigens in a mouse model of C. ruminantium infection. These data identify new recombinant antigens for evaluation in vaccines and diagnostic tests to control heartwater.

Animals↗

Conservation of major surface protein 1 genes of Anaplasma marginale during cyclic transmission between ticks and cattle.

Bovine anaplasmosis is a rickettsial disease of world-wide economic importance caused by Anaplasma marginale. Several major surface proteins with conserved gene sequences have been examined as potential candidates for vaccines and/or diagnostic assays. Major surface protein 1 (MSP1) is composed of polypeptides MSP1a and MSP1b. MSP1a is expressed from the single copy gene msp1 alpha and MSP1b is expressed by members of the msp1 beta multigene family. In order to determine if the msp1 genes are conserved, primers specific for msp1 alpha, msp1 beta(1), and msp1 beta(2) genes were synthesized and used to amplify msp1 sequences of A. marginale from tick cell cultures, from cattle during acute and chronic infections and from salivary glands of Dermacentor variabilis. Protein sequences of MSP1a, MSP1b(1) and MSP1b(2) were conserved during the life cycle of the parasite. No amino acid changes were observed in MSP1a. However, small variations were observed in the MSP1b(1) and MSP1b(2) protein sequences, which could be attributed to recombination, selection for sub-populations of A. marginale in the vertebrate host and/or PCR errors. Several isolate-specific sequences were also observed. Based on the information obtained in this study, the MSP1 protein appears to be fairly well conserved and a potential vaccine candidate.

Amino Acid Sequence↗