Immunodetection of Tropheryma whipplei in intestinal tissues from Dr. Whipple's 1907 patient.
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History, 20th Century↗
Biomedical subjects
Didier Raoult
Publications and source records attributed to Didier Raoult.
Systemic inflammatory responses in African tick-bite fever.
Information regarding the inflammatory response in African tick-bite fever (ATBF), an emerging spotted-fever-group rickettsiosis, in international travelers to sub-Saharan Africa, is scarce. Plasma/serum levels of von Willebrand factor (vWF), soluble (s) E-selectin, tumor necrosis factor-alpha, interleukin (IL)-6, interferon-gamma, IL-10, IL-13, IL-8, RANTES, macrophage inflammatory protein-1alpha, and C-reactive protein were studied, at both first presentation and follow-up, in 15 patients with travel-associated ATBF and in 14 healthy travelers who served as control subjects. Our main and novel findings are the following: (1) patients with ATBF had increased levels of vWF and sE-selectin, with a subsequent decrease at follow-up; (2) with the exception of IFN-gamma, levels of cytokines and chemokines were also increased in these patients at the first presentation; and (3) IL-10 and IL-13 tended to increase during follow-up, whereas most of the inflammatory cytokines decreased. The induction of these mediators and the balance between them may be critical both for the regulation of inflammation and for protective immunity in ATBF.
Adult↗
A giant virus in amoebae.
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Acanthamoeba↗
Cardiac valves in patients with Q fever endocarditis: microbiological, molecular, and histologic studies.
The pathologic features of Q fever endocarditis, which is caused by Coxiella burnetii, were histologically evaluated in cardiac valves from 28 patients. We used quantitative image analysis to compare valvular fibrosis, calcifications, vegetations, inflammation, and vascularization due to Q fever endocarditis with that due to non-Q fever endocarditis and valvular degeneration. We also studied the presence of C. burnetii in valves by immunohistochemical analysis, culture, and polymerase chain reaction (PCR). Histologically, Q fever endocarditis was characterized by significant fibrosis and calcifications, slight inflammation and vascularization, and small or absent vegetations. Despite antibiotic treatment, non-statistically significant variations at the histologic level were observed. These pathologic features could be confused with noninfectious valvular degenerative damage. We found that the detection of C. burnetii in cardiac valves by immunohistochemical analysis, culture, and PCR decreased significantly only after 1 year of antibiotic treatment, which emphasizes the long persistence of this organism in valve tissues. Pathologic and immunohistochemical analyses may contribute to the diagnosis of Q fever endocarditis.
Adult↗
Dysregulation of cytokines in acute Q fever: role of interleukin-10 and tumor necrosis factor in chronic evolution of Q fever.
Q fever manifests as primary infection or acute Q fever and may become chronic in patients with underlying valvulopathy. Because Coxiella burnetii infection depends on host response, we measured tumor necrosis factor (TNF), interleukin (IL)-6, IL-12, and IL-10 in patients with different clinical presentations of acute Q fever. Compared with control subjects, patients with uncomplicated acute Q fever exhibited increased release of the 4 cytokines. Their amounts were higher in patients with hepatitis than in patients with fever or pneumonia. In patients with valvulopathy, who exhibited the highest risk of chronic evolution, the amounts of TNF and IL-10 were higher than in patients without valvulopathy. TNF production was specifically enhanced in patients who developed Q fever endocarditis. These results show that acute Q fever is associated with cytokine overproduction. Persistent TNF amounts were associated with the occurrence of endocarditis in patients with valvulopathy, and that may be a marker of chronic evolution of Q fever.
Adolescent↗
Bartonella quintana bacteremia and overproduction of interleukin-10: model of bacterial persistence in homeless people.
Chronic asymptomatic bacteremia caused by Bartonella quintana occurs in homeless people, but its pathophysiology is unknown. We investigated homeless people with bacteremia to determine whether the persistence of B. quintana is associated with a specific immune profile. Homeless people without B. quintana infection exhibited an inflammatory profile--levels of circulating markers of leukocyte activation (soluble interleukin [IL]-2 receptor and neopterin) and cytokines released by mononuclear cells (tumor necrosis factor, IL-1beta, IL-6, and IL-10) were significantly higher than levels in healthy control subjects. In contrast, homeless people with B. quintana bacteremia exhibited specific increases in IL-10 secretion by mononuclear cells. This overproduction of IL-10 was associated with an attenuated inflammatory profile. The depressed inflammatory response was specific of bacteremia, because patients with specific antibodies and without bacteremia had responses similar to those of homeless people. The overproduction of IL-10 and attenuated inflammatory response may account for the persistence of B. quintana in homeless people.
Adult↗
Outcome and treatment of Bartonella endocarditis.
BACKGROUND: Endocarditis caused by Bartonella species is a potentially lethal infection characterized by a subacute evolution and severe valvular lesions. OBJECTIVES: To evaluate the outcome of patients with Bartonella endocarditis and to define the best antibiotic regimen using the following measures: recovery, relapse, or death. METHODS: We performed a retrospective study on 101 patients who were diagnosed in our laboratory as having Bartonella endocarditis between January 1, 1995, and April 30, 2001. Bartonella infection was diagnosed using immunofluorescence with a 1:800 cutoff, polymerase chain reaction amplification of DNA, and/or culture findings of Bartonella species from whole blood, serum, and/or valvular biopsy specimens. A standardized questionnaire was completed by investigators for each patient. RESULTS: Twelve of the 101 patients died and 2 relapsed. Patients receiving an aminoglycoside were more likely to fully recover (P =.02), and those treated with aminoglycosides for at least 14 days were more likely to survive than those with shorter therapy duration (P =.02). CONCLUSION: Effective antibiotic therapy for Bartonella endocarditis should include an aminoglycoside prescribed for a minimum of 2 weeks.
Adolescent↗
Whipple's disease.
Whipple's disease, or intestinal lipodystrophy, is a systemic infectious disorder affecting mostly middle-aged white men. Patients present with weight loss, arthralgia, diarrhoea, and abdominal pain. The disease is commonly diagnosed by small-bowel biopsy; the appearance of the sample is characterised by inclusions in the lamina propria staining with periodic-acid-Schiff, which represent the causative bacteria. Tropheryma whipplei has been classified as an actinomycete and has been propagated in vitro, which allows the possibility of improving diagnostic strategies, for example through antibody-based detection of the bacillus on duodenal tissue or in circulating monocytes. Cell-mediated immunity in active and inactive Whipple's disease has subtle defects that might predispose some individuals to symptomatic infection with this bacillus, which probably occurs ubiquitously. Although most patients respond well to empirical antibiotic treatment, some with relapsing disease have a poor outlook. The recent findings and concerted research might allow development of new strategies for diagnosis, treatment, and monitoring of patients with Whipple's disease.
Anti-Bacterial Agents↗
Whipple's disease.
Whipple's disease is an infectious disease caused by a gram-positive bacterium, Tropheryma whipplei. The first case was reported in 1907 by GH Whipple. Its classic symptoms are diarrhea and arthralgias, but symptoms can be various. Cardiac or central nervous system involvement, not always associated with digestive symptoms, may also be observed. For a long time, diagnosis has been based on duodenal biopsy, which is positive using periodic acid-Schiff staining. However, for patients without digestive symptoms, results can be negative, leading to a delay in diagnosis. For 10 years, a tool based on polymerase chain reaction targeting the 16S rDNA sequence has been used. In vitro culture of the bacterium, achieved 3 years ago, has allowed new perspectives for diagnosis and treatment. The natural evolution of the disease without treatment is always fatal. Current treatment is based on administration of trimethoprim-sulfamethoxazole for at least 1 year.
Diagnosis, Differential↗
Rhodobacter massiliensis sp. nov., a new amoebae-resistant species isolated from the nose of a patient.
From the nose of a patient with aspiration pneumonia, we isolated a new bacterium by amoebal co-culture using Acanthamoeba polyphaga. Based on phenotypic, 16S rRNA and phylogenetic analysis, we show that this isolate represents a new species within the genus Rhodobacter and and we have named it Rhodobacter massiliensis. The type strain has been deposited in the Collection de l'Institut Pasteur, Paris, France (CIP 107725), and in the Culture Collection of the University of Göteborg, Sweden (CCUG 47968), as strain Framboise.
Acanthamoeba↗
Morphology of Legionella pneumophila according to their location within Hartmanella vermiformis.
The morphology of Legionella pneumophila grown within Hartmanella vermiformis was studied by electron microscopy. Different morphologies were observed, including a replicative form and a mature intracellular form, that had previously been reported in Hela cells. L. pneumophila was also detected within the cyst wall of the amoeba.
Animals↗
Whipple's disease: immunospecific and quantitative immunohistochemical study of intestinal biopsy specimens.
Whipple's disease may be diagnosed by periodic acid-Schiff (PAS) staining, electron microscopy, or polymerase chain reaction of intestinal biopsy specimens. The aim of this study was to evaluate the diagnostic value of immunohistochemistry and the quantification of infected cells in intestinal Whipple's disease. A total of 29 duodenal biopsy specimens from 15 patients with untreated and treated Whipple's disease were examined and compared with biopsy specimens from control patients with normal intestinal mucosa or various pathologic processes. Percentages of staining surfaces with PAS stain and antibodies directed against CD68, a macrophage marker, or the Whipple bacillus, Tropheryma whipplei, were studied quantitatively using a computerized system of image analysis. Positive detection of T. whipplei was obtained using immunohistochemistry in all 15 patients with Whipple's disease. No bacteria were detected in any of the negative controls. The use of quantitative image analysis showed a massive intestinal macrophagic infiltration before (20.3%) and after (13.4%) antibiotic therapy completion as compared with controls (2.1%). The 2 detection methods for T. whipplei, PAS stain and immunohistochemistry, were quantitatively similar before therapy (19.9% versus 17.5%), but the immunodetection-based surface area was significantly lower than the PAS staining surface area after therapy (2.8% versus 7.9%). Our findings indicate that immunohistochemistry is highly specific and sensitive and is applicable as a diagnostic method on intestinal tissue specimens to detect T. whipplei during active infection or in retrospective studies.
Actinobacteria↗
Diagnostic methods. Current best practices and guidelines for identification of difficult-to-culture pathogens in infective endocarditis.
IE is a serious, life-threatening disease. Because treatment must often be adapted to the pathogen involved, rapid identification of the etiologic agent is critical to successful management of each patient. When difficult-to-culture pathogens are involved, routine microbiologic tests, including blood culture, may remain negative. Because such cases may account for up to 31% of all IE cases, alternative diagnostic approaches are necessary. Among the etiologic agents of culture-negative endocarditis, C burnetii and Bartonella spp play a major role; each is responsible for up to 3% of episodes of IE. The authors therefore recommend the systematic use of specific serologies in all cases of clinically suspected endocarditis. The cross-reactivity between C burnetii, Bartonella spp, and Chlamydia spp is of diagnostic importance because all are potential etiologic agents of endocarditis. However, given that the levels of specific antibodies observed in Bartonella endocarditis are extremely high, low-level cross-reactions with other antigens should not lead to misdiagnosis, provided serology for all suspected agents is performed. When serologic test results are negative for both Bartonella spp and C burnetii, special staining by the Gram, Giemsa, Gimenez, PAS, Warthin-Starry, and Grocott methods may guide the use of new diagnostic tools such as PCR and tissue culture for isolation and identification of the causative agent. Such novel approaches may lead to more comprehensive patient evaluations and the discovery of new etiologic agents of IE.
Bacteria↗
Gene-sequence-based criteria for species definition in bacteriology: the Bartonella paradigm.
The definition of new species is currently based on polyphasic classification that includes both determination of phenotypic characteristics and DNA-DNA homology. However, none of these techniques is convenient for the rapid characterization of fastidious or non-culturable bacteria. Using sequences available in the GenBank database, we compared the similarities of gene fragments among the currently recognized Bartonella species. This comparison led to both the definition of similarity values that discriminated Bartonella at the species level and assessment of the relative discriminatory power of each gene examined. In this perspective, rpoB and gltA were found to be the most potent.
Bacteriological Techniques↗
African tick bite fever.
African tick bite fever is an acute febrile illness that is frequently accompanied by headache, prominent neck muscle myalgia, inoculation eschars, and regional lymphadenitis. The disease is caused by Rickettsia africae, a recently identified spotted fever group rickettsia, which is transmitted by ungulate ticks of the Amblyomma genus in rural sub-Saharan Africa and the French West Indies. Whereas reports on African tick bite fever in indigenous populations are scarce, the number of reported cases in travellers from Europe and elsewhere has recently increased significantly. Treatment with doxycycline is associated with rapid recovery in most patients. An immunofluorescence assay is recommended for the diagnosis but seroconversion is commonly delayed and this limits the usefulness of the test. Travellers to endemic areas should be informed of the risk of contracting African tick bite fever and be encouraged to take personal protective measures against tick bites.
Adult↗
The geographical segregation of human lice preceded that of Pediculus humanus capitis and Pediculus humanus humanus.
In order to investigate human-louse phylogeny, we partially sequenced two nuclear (18S rRNA and EF-1 alpha) and one mitochondrial (COI) genes from 155 Pediculus from different geographical origins. The phylogenetic analysis of 18S rRNA and EF-1 alpha sequences showed that human lice were classified into lice from Sub-Saharan Africa and lice from other areas. In both clusters, head and body lice were clearly grouped into two separate clusters. Our results indicate that the earliest divergence within human pediculidae occurred between African lice and other lice, and the divergence between head and body lice was not the result from a single event.
Animals↗
Serosurvey among Mediterranean spotted fever patients of a new spotted fever group rickettsial strain (Bar29).
Mediterranean spotted fever is an endemic disease in Catalonia, Spain. A new spotted fever group (SFG) rickettsial strain (Bar29) of unknown pathogenicity for humans was isolated by our group, in 1996, from the dog brown tick, Rhipicephalus sanguineus. Interestingly, Rickettsia conorii was not isolated in this study. The aim of the present study was to assess the possible pathogenic role of the Bar29 strain. To this purpose, serum samples from 15 patients with Mediterranean spotted fever were obtained and tested by immunofluorescence for antibodies against four related rickettsial strains (R. conorii, R. africae, R. massiliae, and Bar29). Eight of the studied sera reacted at high titers with only R. conorii and Bar29 antigens. For five of the eight sera, the titers against Bar29 were clearly higher than for R. conorii. Four of these sera were also studied by Western blot immunoassay to confirm a specific response. Two of these sera reacted with the high-molecular-mass specific proteins of Bar29 as well as with the low-molecular-mass region (LPS antigen) whereas their reactions with R. conorii were located only on bands of the LPS. This specific response would support the possible pathogenic role of the Bar29 strain for humans. According to this finding, spotted fever caused by R. conorii and rickettsial strain Bar29 may be present in our area. The epidemiological implications of spotted fever caused by R. conorii and by rickettsial strain Bar29 in the Catalonia deserve further studies with isolation and characterization of more rickettsial strains.
Adolescent↗
Coxiella burnetii seropositivity in parturient women is associated with adverse pregnancy outcomes.
OBJECTIVE: We conducted a cohort study of parturient women in an area with endemic Q fever infection to determine whether those seropositive for Coxiella burnetii had evidence of adverse birth outcomes. STUDY DESIGN: From June 1997 to November 1998, the cord blood of all women delivered at our health center was tested for antibodies to C burnetii by indirect immunofluorescence antibody test by using purified whole cell strain Nine Mile antigens. A titer of 1:8 or greater to either phase I or phase II antigens was considered seropositive. Placentas of a sample of cases and seronegative controls had polymerase chain reaction and culture performed. RESULTS: Evidence of prior infection with C burnetii was found in 3.8% (291/7658) of all parturient women. In a multivariate logistic regression, an association was seen between seropositivity (phase I titer >or= 1:8 or phase II titer >or= 1:32) and newborn gestational age >or=36 weeks (phase I antibody, odds ratio [OR] 2.4, 95% CI 1.3-4.3, P =.005; phase II antibody, OR 1.9, 95% CI 1.02-3.7, P =.04). Women with phase I antibody were more likely to have a prior or current neonatal death (phase I OR 3.2, 95% CI 1.09-9.3, P =.03). No placental samples from 153 seropositive or 93 seronegative women had Q fever by polymerase chain reaction or culture. CONCLUSION: About 4% of parturient women in this endemic area have evidence of previous exposure to C burnetii and this exposure is associated with adverse pregnancy outcomes. The pathogenesis of this association remains to be determined.
Adolescent↗