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Cytokine-induced, nitric oxide-dependent, intracellular antirickettsial activity of mouse endothelial cells.

In a murine model of rickettsial disease in which, as in human rickettsioses, endothelial cells are the major target of infection, depletion of IFN-gamma or TNF-alpha converts a sublethal infection into a uniformly fatal disease with overwhelming rickettsial growth and decreased nitric oxide (NO) synthesis. The kinetics of NO production and rickettsial survival and growth were examined on Days 1, 2, and 3 after inoculation of endothelial cells with Rickettsia conorii under four different experimental conditions: (a) no cytokine treatment, (b) treatment with IFN-gamma and TNF-alpha, (c) treatment with cytokines and NG monomethyl-L-arginine, a competitive inhibitor of NO synthesis, and (d) treatment with sodium nitroprusside, a source of NO. Endothelial cells were examined for the presence of inducible nitric oxide synthase mRNA by specific reverse transcriptase-PCR after stimulation with IFN-gamma and TNF-alpha. Cytokine-stimulated and unstimulated rickettsiae-infected endothelial cells were examined by electron microscopy to observe the cellular and rickettsial events. Transformed and diploid mouse endothelial cells stimulated by the combination of recombinant murine IFN-gamma and TNF-alpha killed intracellular Rickettsia conorii by a mechanism that required the synthesis of NO. The antirickettsial effect and NO synthesis were inhibited by treatment of endothelial cells with NG monomethyl-L-arginine. Addition of nitroprusside, which released NO, also exerted a strong antirickettsial effect in the absence of IFN-gamma and TNF-alpha. Endothelial inducible nitric oxide synthase mRNA was detected 4 hours after cytokine stimulation, increased substantially at 8 hours, and decreased to low levels by 72 hours. Ultrastructural evaluation revealed that endothelial cells effected rickettsial killing in association with autophagy. Double membranes of endothelial cell granular endoplasmic reticulum surrounded rickettsiae, which were also observed being destroyed within phagolysosomes. This study demonstrated for the first time that endothelial cells are capable of killing rickettsiae. When stimulated by the combination of IFN-gamma and TNF-alpha, mouse endothelial cells kill Rickettsia conorii by an NO-dependent mechanism. Within the endothelium, NO exerts a rickettsicidal effect.

Animals↗

Rickettsiosis of the genus Rickettsia in South America.

In South America, human cases of infection by the genus Rickettsia have been described in several countries in the last twenty years. The role of international organizations, such as the Centers for Disease Control and Prevention in Atlanta, Georgia, USA and the World Health Organization Collaborating Center for Tropical Diseases at the University of Texas Medical Branch at Galveston, Texas, USA, was very important in the last twenty years for the development of surveillance systems and for the increase in notification of rickettsial diseases by the countries of South America. We hope that the next goal will be prevention and control of rickettsial diseases in the countries of South America, as well as maintaining the programs developed during the last twenty years, so that a good health system and improved social conditions will be possible.

Animals↗

Viruses and rickettsiae.

In this review I shall try to provide a brief, up-to-date, account of the neuropathology of those viral and rickettsial diseases that are particularly prevalent in tropical regions. These diseases are not, however, exclusive to the tropics. Some, such as AIDS, are common in temperate regions as well, though others are closer to being exclusively tropical, such as some of the arthropod-borne (ARBO) virus encephalides. The latter are dependent for their dissemination on an existence during part of their infectious cycle in insects which are, in turn, climatically and seasonally sensitive. This necessarily limits their geographical distribution. Factors that influence some of the other diseases are less closely dependent on climate and geography and reflect more the social or cultural conditions under which people live. Thus, diseases that depend for their spread on forms of human behavior such as promiscuity or drug abuse (AIDS), or poor hygiene and living conditions (polio, rickettsial diseases) or on contact with domestic and other animals (rabies) may occur in a more widespread distribution, for the tropics are not the only places that afford opportunities for these diseases to flourish. I shall select for discussion aspects of the pathology of these diseases that are currently undergoing investigation but will aim to present these against the backdrop of more established aspects of their pathology. Recent reviews of the pathology of viral encephalitis can be found in Hamilton and Wiley (33) and Esiri and Kennedy (20) and of HIV-1 infection in Price & Sidtis (78) and Scaravilli (85).

AIDS Dementia Complex↗

[Richettsial pericarditis and pleurisy].

The authors report two cases of rickettsial disease due to R. Conori with mainly pericarditis in one case, sero-fibrinous pleurisy in the other. They then recall a few general data concerning this rickettsial disease and the very restricted place that it occupies in the etiology of pericarditis and, even more so, in the case of pleurisy. The conditons of diagnosis, which are mainly serological, are discussed, in particular with regard to pericarditis and tuberculous pleurisy.

Acute Disease↗

[Rickettsiosis of the typhus fever type. Its joint appearance with a left-ventricular thrombus and single-vessel coronary disease].

A 44-year-old German fell ill in Libya, where he had been living for 10 years, with high fever, rigor and a nonitching centrifugally spreading macular rash, which had spared the head, hands and soles. In addition, a systolic cardiac murmur was heard. The Weil-Felix reaction had a titre rising within 3 days from 1:160 to 1:640, confirming the diagnosis of rickettsial disease, the total clinical picture indicating typhus. On treatment with chloramphenicol (1 g three times daily i.v.) the fever subsided within 5 days. On the ninth day treatment was changed to oral doxycyclin, 200 mg daily for 3 weeks. Echocardiography surprisingly revealed a floating thrombus, about 4 x 8 cm, attached to the hypo- and even akinetic apex of the left ventricle. In addition there was single-vessel coronary disease. Since the segmental contraction abnormality persisted after the typhus had been cured, a causal connection with the rickettsial disease is unlikely. The thrombus was removed at the time of a aortocoronary bypass operation: his course has been unremarkable since then.

Adult↗

The ocular manifestations of Rocky Mountain spotted fever.

To our knowledge, this is the first report of an iris nodule in a case of Rocky Mountain spotted fever (RMSF). The iris nodule may be similar to the "typhus nodule" of the central nervous system reported at autopsy in patients with typhus rickettsial disease. Previous case reports of RMSF have emphasized either anterior uveitis or retinal vasculitis. In the case reported here, both occurred in our patient as a result of RMSF. Also, we review the ophthalmic literature on rickettsial disease.

Adult↗

Seroprevalence of murine typhus and fièvre boutonneuse in certain human populations in Egypt.

A study was conducted between 1984 and 1987 to determine the prevalence of Rickettsia typhi and Rickettsia conorii infections among humans residing in the Nile Delta, Suez Canal area and Nile Valley of Egypt. Serum specimens were obtained from garbage and rodent control workers, other unclassified occupational workers, and from patients with fever of undetermined aetiology. All sera were assayed for IgA + IgM + IgG (IgAMG) antibody mixture and if positive, reassayed for specific IgM antibody to rickettsia by the indirect fluorescent antibody technique. R. typhi antibody was found in 19% (33/178) of the garbage collectors, whereas only 1% (2/178) had demonstrable antibody to R. conorii. Among those with other occupations, R. typhi antibody was detected in 0.7% (2/295) and none had R. conorii antibody. The antibody prevalence rate for R. typhi among patients with febrile illness ranged from 25 to 41%, and from 2 to 15% for R. conorii, at three different locations in Egypt. In addition, IgM antibody to R. typhi was demonstrated in some patients showing symptoms compatible with rickettsial disease and in some patients who seroconverted, indicating that R. typhi was the cause of illness among some of these patients. These findings support previous observations that R. typhi and R. conorii are the causes of human rickettsial disease in Egypt, and that humans are commonly infected with R. typhi.

Adult↗

[Rickettsia africae infection. Three cases confirmed by PCR].

BACKGROUND AND OBJECTIVE: African tick bite fever or Rickettsia africae infection has been recognized as an emerging health problem in the last few years. The aim of this study was to describe 3 cases of Spanish tourists who suffered from R. africae infection after visiting South Africa. PATIENTS AND METHOD: Three patients with a suspected rickettsial disease according to epidemiological and clinical manifestations (fever, eschar and exanthema) were studied. Antibodies against Rickettsia conorii were determined by IFI assays. Semi-nested PCR reactions (rOmpA) and subsequent sequence analysis of the amplified products were also carried out. RESULTS: Epidemiological and clinical aspects of this rickettsiosis are described. For diagnosis of this rickettsial disease, conventional serological assays (IFI) were less useful than semi-nested rOmpA PCR reactions, which showed a sensitivity of 100% in our samples. CONCLUSIONS: Three cases of R. africae infection are reported. PCR and subsequent sequencing of the amplicons are useful for the microbiological confirmation of this type of infection. We must think about African tick-bite fever as a possible diagnosis in patients with a febrile rash after returning from endemic areas.

Adult↗

[Tropical animal and human rickettsial infections].

Advances in molecular biology have provided tools that have greatly clarified our knowledge of rickettsial diseases. Most rickettsias have been reclassified in the alpha subgroup of proteobacteria. Four groups of rickettsias have been identified: the spotted fever group, the typhus group, Ehrlichia, and Bartonella. Although still considered as a rickettsia, Coxiella burnetti, the agent causing Q fever, has been reclassified separately in the gamma subdivision of proteobacteria. Recognition of rickettsial disease is still based mainly on clinical manifestations (rash, eschar, and scratching sores). Little progress has been made in serologic testing. Indirect immunofluorescence is the most common technique. Diagnostic techniques based on molecular biology are currently available in only a small number of laboratories. Treatment with tetracyclines is indicated but prophylaxis through proper hygiene is the most effective approach.

Animals↗

Rickettsial infections--a threat to travellers?

PURPOSE OF REVIEW: Recent developments in cell-culture techniques and molecular methods have led to the description of several new rickettsial diseases. An update on these new infections should be of interest to health workers with patients who are international travellers. RECENT FINDINGS: Epidemic typhus was reported last year in the United States when an outbreak of murine typhus was recorded in Hawaii. Among spotted fever group rickettsioses, African tick bite fever is now probably the most common rickettsial infection in Africa with numerous cases also reported in international travellers. For the first time the Astrakhan fever rickettsia has been described outside Europe, in a French patient returning from Chad. Similarly, the first case of Rickettsia sibirica mongolotimonae infection in Africa was reported in 2004. Finally, a newly recognized agent of a spotted fever rickettsiosis, Rickettsia parkeri, has been reported in the United States during 2004. SUMMARY: Because results of serological testing are only presumptive, sophisticated methods are crucial for the diagnosis and description of new rickettsial diseases, especially in atypical cases. Modern diagnostic tools include cross-adsorption assays, Western blot testing, and cell-culture and molecular-biological methods.

Animals↗

Rickettsia africae, a tick-borne pathogen in travelers to sub-Saharan Africa.

BACKGROUND: African tick-bite fever occurs after contact with ticks that carry Rickettsia africae and that parasitize cattle and game. Sporadic reports suggest that this infection has specific clinical and epidemiologic features. METHODS: We studied patients who were tested for a rickettsial disease after returning from a visit to Africa or Guadeloupe. To assess the value of the microimmunofluorescence assay, Western blotting, and cross-adsorption assays, we compared the results of these tests in 39 patients in whom African tick-bite fever had been confirmed by the polymerase-chain reaction assay, cell culture, or both; 50 patients with documented R. conorii infection; and 50 blood donors. These diagnostic criteria were then applied to 376 additional patients who had returned from southern Africa and 2 who had returned from Guadeloupe and whose serum was being tested for rickettsial disease. RESULTS: In the 39 patients with direct evidence of R. africae infection, the combination of microimmunofluorescence assay, Western blotting, and cross-adsorption assays showing antibodies specific for R. africae had a sensitivity of 0.56; however, each test had a positive predictive value and a specificity of 1.0. An additional 80 patients were found to have an R. africae infection on the basis of these serologic criteria. Infections with R. africae were acquired by visitors to 11 African countries and Guadeloupe. The illness was generally mild and was characterized by a rash in 46 percent of the patients; the rash was usually maculopapular or vesicular and rarely purpuric. Ninety-five percent of patients had an inoculation eschar or eschars, and 54 percent of these patients had multiple eschars, a finding that is unusual in patients with rickettsial infection. CONCLUSIONS: In this series, R. africae was the cause of nearly all cases of tick-bite rickettsiosis in patients who became ill after a trip to sub-Saharan Africa.

Adolescent↗

Rickettsial skin disease: uncommon presentations.

Rickettsioses occurring worldwide show a significant morbidity and mortality when not properly treated. Early diagnosis is mandatory for better outcome. Clinical symptoms and patient's history are essential, but uncommon presentation of these arthropod-borne diseases may be a challenge.

Anti-Bacterial Agents↗

A case of laboratory-acquired murine typhus.

We encountered a 32-year-old Korean woman who developed murine typhus in a laboratory. She worked as a technician in a laboratory for rickettsial disease. Immunofluorescence test with rickettsial antigen (R. typhi) was positive at 1: 320 on admission and 1: 1280 after 4 weeks. A dose of 200 mg of doxycycline for 7 days proved to be effective for her condition.

Adult↗

Bovine petechial fever (Ondiri disease).

Bovine petechial fever is a Rickettsial disease of cattle, which has been diagnosed, only in Kenya, East Africa. Other countries in the region share some of the biotopes in which the disease occurs, and may well have the infection. The disease is characterised by widespread petechial and ecchymotic haemorrhages on the mucosal surfaces, and throughout the serosal and subserosal surfaces of the body organs and cavities. It may be fatal in up to 50% of untreated cases. The causal organism may be demonstrated most readily in the cytoplasm of polymorphonuclear granulocytes of the peripheral blood, as well as other leucocytes, and has been classified as Cytoecetes ondirii, a member of the tribe Ehrlichiae. Circumstantial and other evidence suggests that the disease is transmitted by an arthropod vector, which has yet to be identified. The blood of a naturally infected wild ruminant, the bushbuck, Tragelaphus scriptus has been shown to remain infective for at least 2 years, and other species such as the African buffalo, Syncercus caffer for at least 5 weeks. These and possibly other species, may serve as the amplifying and reservoir hosts.

Anaplasmataceae↗