[Diagnostic value of the Mantoux test in cases of inflammations of the mesenchymal tissue of the eye, treated with typhus vaccine].
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A patient presented after a trip to South Africa with a febrile illness and rash that was consistent with either rickettsialpox or mild boutonneuse fever. The clinical, laboratory, and geographic overlap of these diseases makes differentiation difficult in certain situations. Several different rickettsial infections may cause an eschar and a rash that may be papulovesicular. From a clinical perspective, distinguishing these diseases is not critically important as long as therapy with tetracycline is implemented. More precise identification of the etiologic agent could be required in certain military situations because the preventive measures employed for some of these diseases may be significantly different.
A short review of past and recent works pertinent to the etiology and pathogenesis of infectious mononucleosis is presented. Epidemiological studies have led to the elaboration of hypotheses concerning the etiology, the length of the incubation period and the mode of transmission of the disease. An unusual type of infectious mononucleosis of rickettsial origin has been reported by Japanese workers. Studies of accidental and experimental transmission suggest that more than one agent may give rise to the same disease. Isolation attempts in tissue cultures have been unrewarding except for the uncovering of possible agents by interference and immunofluorescence.The atypical lymphocyte is the site of increased RNA and DNA synthesis. It does not seem to be involved in antibody synthesis. The heterophile agglutinins and other mononucleosis-associated antibodies apparently account for only part of the excess 19S antibody material found in mononucleosis sera. The origin and function of these antibodies and of the atypical lymphocyte are the subject of speculation.The final elucidation of the pathogenesis of the disease and the confirmation of the reviewed hypotheses are all dependent on the eventual discovery of the elusive etiological agent(s) of infectious mononucleosis.
The immune response in human tsutsugamushi disease (scrub typhus) was studied. Anti-rickettsial activity of sera, peripheral mononuclear cells and their culture supernatants from patients on in vitro growth of Rickettsia tsutsugamushi proliferating in normal human peripheral macrophages was examined. The results obtained were as follows. 1) Sera from patients at the early convalescent stage, which exhibited high antibody titers against R. tsutsugamushi, effectively inhibited their growth in macrophages. 2) Sera from patients after a long period from the onset showed low antibody titers and did not inhibit rickettsial growth. 3) Mononuclear cells and T cell enriched fractions suppressed rickettsial growth when they were obtained from the patients at the early convalescent stage and even after as long as 3.5 years from the onset. 4) The culture supernatants of the T cell-enriched fractions which were collected from the patients mentioned above, exhibited a similar antirickettsial activity. These findings indicate that sensitized T lymphocytes and macrophages might play a fundamental role in immunological defense mechanism in tsutsugamushi disease. And the results obtained in our experiments are compatible with those previously reported in experimental scrub typhus in laboratory animals such as mice and monkeys.
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Following biosynthesis, class II MHC molecules are transported through a lysosome-like compartment, where they acquire antigenic peptides for presentation to T cells at the cell surface. This compartment is characterized by the presence of HLA-DM, which catalyzes the peptide loading process. Here we report that the morphology and function of the class II loading compartment is affected in diseases with a phenotypic change in lysosome morphology. Swollen lysosomes are observed in cells from patients with the hereditary immunodeficiency Chediak-Higashi syndrome and in cells infected with Coxiella burnetii, the rickettsial organism that causes Q fever. In both disease states, we observed that HLA-DR and HLA-DM accumulate in enlarged intracellular compartments, which label with the lysosomal marker LAMP-1. The distribution of class I MHC molecules was not affected, localizing disease effects to the endocytic pathway. Thus, cellular mechanisms controlling lysosome biogenesis also affect formation of the class II loading compartment. Analysis of cell surface class II molecules revealed that their steady-state levels were not reduced on diseased cells. However, in both disease states, enhanced interaction between HLA-DR and HLA-DM was detected. In the Chediak-Higashi syndrome cells, this correlated with more efficient removal of the CLIP peptide. These findings suggest a mechanism for perturbation of Ag presentation by class II molecules and consequent immune deficiencies in both diseases.
Thirty-eight monoclonal antibodies that have not been reported previously were developed from mice immunized with Rickettsia rickettsii, R. conorii, and R. sibirica. Western immunoblotting showed that these monoclonal antibodies are directed against heat-sensitive epitopes which are located on two major surface polypeptides with molecular sizes ranging from 115 to 150 kilodaltons. The detection of the two bands did not depend on the presence of 2-mercaptoethanol. Both bands were destroyed by treatment with proteinase K. Monoclonal antibodies examined by immunofluorescence assay reacted with epitopes that are species specific, group reactive, or shared among a smaller subset of species of spotted fever group rickettsiae. Nine of the monoclonal antibodies were evaluated for their ability to neutralize rickettsial infection and thus protect animals against disease caused by homologous species of rickettsiae. Treatment of rickettsiae with monoclonal antibodies F3-12, F3-14, and F3-36 completely protected guinea pigs against illness caused by the homologous organism R. rickettsii. Monoclonal antibodies F9-5G11 and F15-5B12, derived from mice immunized with R. sibirica, conferred partial protection by delaying the onset and shortening the duration of fever in guinea pigs inoculated with R. sibirica. Monoclonal antibodies F2-15, F2-31, F2-53, and F3-12 protected mice from a lethal infection with R. conorii. Heat-labile epitopes of spotted fever group rickettsial surface proteins are important candidate antigens for development of vaccines to confer protective immunity.
Between November 1993 and March 1994, a cluster 6 pediatric patients with acute febrile illnesses associated with rashes was identified in Jujuy Province, Argentina. Immunohistochemical staining of tissues confirmed spotted fever group rickettsial infection in a patient with fatal disease, and testing of serum of a patient convalescing from the illness by using an indirect immunofluorescence assay (IFA) demonstrated antibodies reactive with spotted fever group rickettsiae. A serosurvey was conducted among 16 households in proximity to the index case. Of 105 healthy subjects evaluated by IFA, 19 (18%) demonstrated antibodies reactive with rickettsiae or ehrlichiae: 4 had antibodies reactive with Rickettsia rickettsii, 15 with Ehrlichia chaffeensis, and 1 with R. typhi. Amblyomma cajennense, a known vector of R. rickettsii in South America, was collected from pets and horses in the area. These results are the first to document rickettsial spotted fever and ehrlichial infections in Argentina.
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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.
In the late 1970s, a new infectious disease in horses, involving acute enteritis, was recognised in the Potomac River area of Maryland, U.S.A. The causative agent was identified subsequently as a new species of rickettsial organism, later named Ehrlichia risticii. Since then, the disease has been reported in many other states, and in enzootic areas vaccination is common. Signs associated with the clinical disease included depression, fever, anorexia, decreased or absent intestinal sounds, profuse watery diarrhoea and laminitis. However, considerable variation in clinical manifestations has been reported in both the natural and experimental disease. Accurate diagnosis depends on serological testing; currently, the immunofluorescent antibody test (IFA) is used widely, although an enzyme-linked immunosorbent assay (ELISA) has been developed recently. Mortality in untreated cases is 15 to 35 per cent. Antibiotics of the tetracycline series have shown activity against the organism in vitro, in an in vivo murine model and appear to be useful in clinical cases.
The serum of subjects with multiple sclerosis or other degenerative neurological diseases and that of normal controls does not differ significantly in its content of antibodies to several rickettsial antigens. There is no evidence for a rickettsial aetiology of multiple sclerosis, and no grounds for an extended clinical trial of Le Gac's full method of treatment with antibiotics.
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Rickettsioses are among the most frequent causes of febrile diseases in travelers, as shown in several studies in the last years. Furthermore, since 1991, with the introduction of new testing methods, 8 new Rickettsia species (or new diseases) have been described. Typical symptoms of rickettsial infections are high fever, headaches and myalgias, frequently associated with a rash and/or an inoculation eschar ("tache noire") at the site of tick bite. The rapid recognition of a rickettsiosis and the immediate start of appropriate antibiotic therapy are important because some rickettsioses (e. g. the Rocky Mountain spotted fever) are associated with relevant morbidity and mortality. This paper reviews the spotted fever group rickettsioses.
Tick-borne rickettsial infections are responsible for many emerging diseases in humans and several vertebrates. These include human infections with Ehrlichia chaffeensis, Ehrlichia ewingii and Anaplasma phagocytophilum. As single or co-infections can result from a tick bite, the availability of a rapid, multiplex molecular test will be valuable for timely diagnosis and treatment. We recently described a muliplex-molecular test that can detect single or co-infections with up to five Ehrlichia and Anaplasma species. We reported that the test has the sensitivity to identify single infections in the canine host with E. chaffeensis, E. canis, E. ewingii, A. phagocytophilum, and A. platys and co-infection with E. canis and A. platys. In this study, ticks were collected from different parts of the state of Kansas during summer months of the year 2003 and tested for the presence of infection using the molecular test. The analysis revealed a minimum of 3.66% of the ticks to be positive for either E. chaffeensis or E. ewingii in A. americanum and Dermacenter species. This assay will be valuable in monitoring infections in dogs and ticks, and with minor modifications it can be used for diagnosing infections in people and other vertebrates.
African tick-bite fever (ATBF) is a rickettsiosis caused by Rickettsia africae. We describe histologic features and immunodetection of R. africae in cutaneous inoculation eschars from 8 patients with ATBF, which was diagnosed by culture or association of positive PCR detection and positive serologic results. We used quantitative image analysis to compare the pattern of inflammation of these eschars with those from Mediterranean spotted fever. We evaluated the diagnostic value of immunohistochemical techniques by using a monoclonal antibody to R. africae. ATBF eschars were histologically characterized by inflammation of vessels composed mainly of significantly more polymorphonuclear leukocytes than are found in cases of Mediterranean spotted fever (p < 0.05). Small amounts R. africae antigens were demonstrated by immunohistochemical examination in 6 of 8 patients with ATBF. Neutrophils in ATBF are a notable component of the host reaction, perhaps because ATBF is a milder disease than the other rickettsioses. Immunohistochemical detection of rickettsial antigens may be useful in diagnosing ATBF.
The role of the immune response in the pathogenesis of Rickettsia rickettsii infection in guinea pigs was investigated by immunosuppression, using antilymphocyte serum. Twenty guinea pigs were inoculated with R. rickettsii, Sheila Smith strain, on day 0. Fifteen animals received antilymphocyte serum on days --1, 0, 2, 4, and 6. Five animals received normal rabbit serum on the same schedule. At necropsy, specimens were collected for histological examination, rickettsial immunofluorescence, rickettsial titration, and antirickettsial antibody titration. All normal rabbit serum recipients and 12 of 15 antilymphocyte serum recipients developed typical disease. Comparison of animals in terminal stages of disease revealed the same clinical course and gross lesions, but differing rickettsial burden and cellular response. Immunosuppressed animals had higher titers of splenic rickettsiae and greater numbers of immunofluorescent rickettsiae. Thus, although antibody was undetectable in both groups, there appeared to be an inhibition of antirickettsial immunity. Microscopic vasculitis was similar quantitatively, but differed qualitatively, with immunocompetent animals having the typical monouclear/lymphocytic inflammation and immunosuppressed animals having neutrophilic predominance. This study demonstrates that immunopathological mechanisms are not necessary for the pathogenesis of experimental Rocky Mountain spotted fever. The rickettsiae themselves seem capable of causing cellular and tissue damage.
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