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Activation and apoptosis of macrophages in cat scratch disease.

Cat scratch disease is an infectious disease usually caused by Bartonella henselae. Within 1-3 weeks after inoculation, patients typically develop regional self-limited lymphadenopathy. Lymph nodes reveal granulomas consisting of central necrosis, an inner rim of palisading macrophages, and an outer rim of lymphocytes and non-palisading macrophages. In animals, cat-scratch disease leads to an interferon-gamma (IFNgamma)-mediated T-helper 1 immune response, resulting in macrophage recruitment, stimulation, and thereby granuloma formation. The present study has sought to find in situ evidence for macrophage migration, activation, and cell death in human cat scratch disease. By non-radioactive in situ hybridization and immunohistochemistry on serial sections, it was demonstrated that IFNgamma+ T lymphocytes and S100A8+, S100A9+ macrophages embrace granulomas, which consisted of S100A8-, S100A9-, HLA-DR+, CD40+, TNFalpha+ macrophages. Combination of in situ end-labelling and immunofluorescence revealed large numbers of DNA-fragmented CD68+ cells with intact plasma membranes corresponding to apoptotic macrophages. On the basis of these data, it was hypothesized that in human cat scratch disease, S100A8+, S100A9+ macrophages continuously migrate to the granulomas. During this process, they may be activated by IFNgamma T-helper 1 lymphocytes and be differentiated to S100A8-, S100A9-sessile, HLA-DR+, CD40+ antigen-presenting, TNFalpha+ pro-inflammatory macrophages forming granulomas. In parallel, macrophages undergo apoptosis in the centre of granulomata, a phenomenon that may restrict the destructive potential of macrophages and contribute to self-limitation of cat scratch disease.

Apoptosis↗

Haemobartonellosis in squirrel monkeys (Saimiri sciureus): antagonism between Haemobartonella sp. and experimental Plasmodium falciparum malaria.

A hemotropic parasite of the genus Haemo bartonella (rickettsial parasite of the Family Anaplasmataceae) is responsible for latent asymptomatic infection in colony-born Saimiri monkeys. Indeed, many of these animals develop a patent Haemobartonella infection following splenectomy. Such patent parasitism is characterized by an intense Haemobartonella parasitemia which peaks between days 12 and 14 after removal of the spleen and then decreases to become undetectable between days 25 and 30. During the resolving phase of parasitemia, a moderate anemia associated with monocytosis and erythrophagocytosis is observed. In certain Saimiri monkeys, Haemobartonella parasitemia remains latent following removal of the spleen. This indicates that the spleen plays a role but is not necessary to maintain latent Haemobartonella parasitism. It also suggests the existence of heterogeneity in the host immune reactivity to the parasite. Latent or patent haemobartonellosis might raise a problem when Saimiri monkeys are used as experimental hosts of Plasmodium falciparum asexual blood stages, as already noticed with "rodent malaria." Thus we investigated the relationship between Haemobartonella and P. falci parum in splenectomized monkeys. When animals harboring latent Haemobartonella sp. were infected with P. falciparum, the former remained latent and exerted no influence on the course of the P. falciparum parasitemia. In constrast, when P. falciparum was initiated in animals which were in the process of developing patent haemobarto nellosis, the course of the former was protracted and either the animal resisted longer, or it self-cleared the P. falciparum infection. Conversely, patent haemobartonellosis was delayed when splenectomy was performed at different times after initiation of P. falciparum infection in intact monkeys. Our results do not allow us to draw conclusions as to the mechanism(s) of the antagonism between the two parasites, but they emphasize the need to monitor the presence of Haemobartonella when splenectomized Saimiri monkeys are used as experimentals hosts for P. falciparum parasitism.

Anaplasmataceae Infections↗

Carboxyl-terminal processing protease for the D1 precursor protein: cloning and sequencing of the spinach cDNA.

A previous study has demonstrated that the carboxyl-terminal (C-terminal) processing protease in spinach for the D1 precursor protein (pDl) of the photosystem II reaction center is a monomeric protein of about 45 kDa. Based on the amino acid sequence data of the purified protease, a cDNA clone encoding the enzyme has been identified and sequenced, from a spinach green leaf cDNA library. In order to determine the 5' end of the transcript, the rapid amplification of cDNA end (5'-RACE) technique was applied. By these analyses, the full-length transcript was established to consist of 1906 nucleotides and a poly(A) tail, containing an open reading frame (ORF) corresponding to a protein with 539 amino acid residues. By comparing the amino acid sequence of the purified protease with that deduced from nucleotide sequence of the cDNA clones, the enzyme was shown to be furnished with an extra amino-terminal extension characteristic of both a transit peptide and a signal sequence. This suggests that the protease is synthesized in the cytosol and translocated into the lumenal space of thylakoids. The mature part of the enzyme consists of 389 amino acid residues and exhibits a significant sequence homology with two groups of proteins as demonstrated by a computer homology search, i.e. (1) the deduced sequence of a protein proposed to be the C-terminal processing protease for pD1 in Synechocystis sp. PCC 6803, based on genetic experiments and (2) proteases for C-terminal cleavage identified in Escherichia coli and Bartonella bacilliformis.

Algal Proteins↗

[Immunobiology of tuberculosis].

R. Koch showed in 1882 in his so-called fundamental experiment that tuberculous guinea pigs exhibit a vigorous immunity against re-infection. In investigations in 1930--40 we showed that this immunity is not mediated by humoral antibodies. It is a cellular process, a local and general activation of the macrophage system (the system of mononuclear phagocytes). The tuberculous granuloma consists of activated macrophages and their descendants (epitheloid and giant cells), which inhibit the growth and spreading of tubercle bacilli. The role of the specific and unspecific activation of the macrophage system could be demonstrated in experiments on rats, infected with Bartonella muris ratti. These early results are related to the recent knowledge concerning cellular immunity and granulomatous inflammation, especially to the cooperation between the lymphatic and macrophage system.

Anaplasmataceae↗

Cutaneous bacillary angiomatosis.

Bacillary angiomatosis is characterized by unique vascular lesions caused by infection with a small Gram staining bacillus of the genus Bartonella. It usually occurs in immunocompromised persons but can also occur in immunocompetent persons. We report a case of cutaneous bacillary angiomatosis in a 5-year-old immunocompetent child. He had infected lesions on the lips, after an injury, which was followed by lesions over the knees, buttocks, near the ankles and the elbows. Diagnosis was proved on histology. The lesions cleared after administration of erythromycin for 3 months. It is well to be aware of this condition in the context of increasing prevalence of AIDS.

Angiomatosis, Bacillary↗

Characterization of the human autoimmune response to the major C-terminal epitope of the ribosomal P proteins.

Autoantibodies to the ribosomal phospho (-P) proteins P0, P1, and P2, collectively referred to as Rib-P, are specifically found in 10-40% of patients with systemic lupus erythematosus (SLE). These antibodies are believed to be correlated with lupus nephritis, hepatitis, and central nervous system involvement. The major immunoreactive epitope of these ribosomal antigens has been localized to the carboxy terminus, which is a highly conserved domain of all three proteins and contains two phosphorylated serine residues. The phosphorylated amino acids of the P proteins are known not to be critical epitope determinants. Furthermore, epitope-mapping studies have shown that the major epitope is located within the last 11 C-terminal amino acids. Using peptide arrays we identified more precisely this shared epitope as the six C-terminal amino acids GFGLFD and elucidated the molecular recognition events of anti-Rib-P antibodies at the amino acid level. We identified Phe(111) and Phe(114) of Rib-P2 as the key residues for the interaction, with further contributions of Gly-112 and Asp-115. This amino acid stretch is also present in proteins of several pathogenic micro-organisms such as Trypanosoma cruzi, Brugia malayi, Pseudomonas aeruginosa, Candida albicans, several Leishmania species, and Bartonella henselae. Using newly developed ELISA systems with a C-terminal peptide (C22) and the recombinant proteins (P0, P1, and P2) as antigens we found a high specificity of anti-Rib-P antibodies for SLE and demonstrated positive correlations with anti-U1-C, anti-Sm-B/B' and anti-D and anti-dsDNA antibodies. The sensitivity and specificity in the peptide (C22) based assay varied between 12.8%/100% and 23.4%/96.7% for SLE, depending on the assigned cutoff. In contrast to other studies, we found no significant correlation of anti-Rib-P reactivity with central nervous system manifestations or renal involvement in SLE patients. We conclude that the epitope motif GFGLFD in the C-termini of the ribosomal P proteins is the key determinant of anti-Rib-P antibodies, and that the C22 peptide and the recombinant proteins can be used equally well for the detection of anti-Rib-P antibodies. The role of the major Rib-P epitope in the development of anti-ribosomal P antibodies and in the pathogenesis of SLE remains a subject of further investigation.

Amino Acid Sequence↗

Development of IgA nephritis following cat scratch disease in a 13-year-old boy.

We describe a 13-year-old boy who presented with hematuria and intermittent low-grade proteinuria at the time when he was diagnosed with cat scratch disease. Two months before presentation, he had a negative urinalysis during a routine physical evaluation. He continued to have microscopic hematuria for the next 6 months, when he developed gross hematuria and recurrence of low-grade proteinuria. The renal biopsy showed evidence of mild/moderate IgA nephropathy. We speculate that the immunological changes associated with cat scratch disease in this patient may have triggered the development of IgA nephropathy. A history or serological evidence of infection with Bartonella henselae may need to be sought in patients presenting with IgA nephritis.

Adolescent↗

Osteomyelitis of the hip joint associated with systemic cat-scratch disease in an adult.

Reported here is the case of a 29-year-old male with cervical lymphadenopathy, fever and weight loss, followed by acute painful osteomyelitis of the left hip joint due to cat-scratch disease. The diagnosis was established by detection of IgG antibodies to Bartonella henselae in serum and histologic examination of a lymph node including a positive polymerase chain reaction test. Treatment consisted of clarithromycin and cefotiam for 2 weeks. Four weeks after discharge, all of the patient's symptoms had completely resolved. Magnetic resonance imaging of the left hip joint showed marked regression of bone inflammation 4 months later and normalization after 8 months. Cat-scratch disease should be considered in the differential diagnosis of osteomyelitis in an adult, especially when lymphadenitis is present.

Adult↗

Cat scratch disease: analysis of 130 seropositive cases.

To clarify the clinical manifestations of cat scratch disease (CSD), we evaluated a total of 130 seropositive patients with CSD. The patients' ages ranged from 1 to 68 years; 103 (79.2%) were under 18 years of age. CSD occurred predominantly in the fall and winter months. Regional lymphadenopathy was noted in 110 (84.6%) of the cases, and the most common sites were the neck (33%), axillary (27%), and inguinal (18%) regions. One hundred of the patients (77%) had general symptoms, such as fever, headache, and malaise. The clinical manifestations of CSD showed a wide spectrum from typical or classical CSD, with regional lymphadenopathy, to atypical or systemic CSD. Of the 130 cases, 103 (79.2%) were typical CSD and 27 (20.8%) were atypical CSD. Atypical cases of CSD were commonly reported as fever of unknown origin (37.0%), neuroretinitis (22.2%), encephalopathy (14.8%), hepatosplenic granuloma (11.1%), and Parinaud's oculoglandular syndrome (7.4%). Fever of unknown origin or prolonged fever lasting more than 14 days was evident in 27 (20.8%) of the 130 cases in this study. Eleven of the 27 cases lacked lymphadenopathy. Our findings suggest that CSD is not a rare disease in Japan. The indirect fluorescent antibody (IFA) test to detect Bartonella species may provide a prompt diagnosis of CSD and facilitate appropriate therapy.

Adolescent↗

Borrelia, Coxiella, and Rickettsia in Carios capensis (Acari: Argasidae) from a brown pelican (Pelecanus occidentalis) rookery in South Carolina, USA.

Argasid ticks are vectors of viral and bacterial agents of humans and animals. Carios capensis, a tick of seabirds, infests the nests of brown pelicans, Pelecanus occidentalis, and other ground nesting birds along the coast of South Carolina. This tick is associated with pelican nest abandonment and could pose a threat to humans visiting pelican rookeries if visitors are exposed to ticks harboring infectious agents. We collected ticks from a pelican rookery on Deveaux Bank, South Carolina and screened 64 individual ticks, six pools of larvae, and an egg mass for DNA from Bartonella, Borrelia, Coxiella, and Rickettsia by polymerase chain reaction amplification and sequencing. Ticks harbored DNA from "Borrelia lonestari", a novel Coxiella sp., and three species of Rickettsia, including Rickettsia felis and two undescribed Rickettsia spp. DNA from the Coxiella and two undescribed Rickettsia were detected in unfed larvae that emerged in the laboratory, which implies these agents are transmitted vertically by female ticks. We partially characterize the novel Coxiella by molecular means.

Animals↗

Rickettsial agents in Egyptian ticks collected from domestic animals.

To assess the presence of rickettsial pathogens in ticks from Egypt, we collected ticks from domestic and peridomestic animals between June 2002 and July 2003. DNA extracts from 1019 ticks were tested, using PCR and sequencing, for Anaplasma spp., Bartonella spp., Coxiella burnetii, Ehrlichia spp., and Rickettsia spp. Ticks included: 29 Argas persicus, 10 Hyalomma anatolicum anatolicum, 55 Hyalomma anatolicum excavatum, 174 Hyalomma dromedarii, 2 Hyalomma impeltatum, 3 Hyalomma marginatum rufipes, 55 unidentified nymphal Hyalomma, 625 Rhipicephalus (Boophilus) annulatus, 49 Rhipicephalus sanguineus, and 17 Rhipicephalus turanicus. Ticks were collected predominantly (>80%) from buffalo, cattle, and camels, with smaller numbers from chicken and rabbit sheds, sheep, foxes, a domestic dog, a hedgehog, and a black rat. We detected Anaplasma marginale, Coxiella burnetii, Rickettsia aeschlimannii, and four novel genotypes similar to: "Anaplasma platys," Ehrlichia canis, Ehrlichia spp. reported from Asian ticks, and a Rickettsiales endosymbiont of Ixodes ricinus.

Animals↗

Bacillary angiomatosis of the cervix and vulva in a patient with AIDS.

BACKGROUND: Bacillary angiomatosis is a clinicopathologic entity that most often is identified in the skin of patients with AIDS. This report presents an example of bacillary angiomatosis of the female genital tract. CASE: Bacillary angiomatosis presented as red-purple nodules of the vulva and cervix in a 32-year-old woman with AIDS. Histologic examination revealed the lobular epithelioid vascular proliferation and hazy clumps of bacteria that characterize bacillary angiomatosis. The diagnosis was confirmed on Warthin-Starry-stained issue and by blood cultures, which were positive for Bartonella (Rochalimaea) henselae. CONCLUSION: Accurate diagnosis of this infection is important because 1) bacillary angiomatosis is commonly mistaken for Kaposi sarcoma, 2) it is effectively treated with inexpensive antibiotics, and 3) undiagnosed and/or untreated bacillary angiomatosis may lead to overwhelming disseminated infection and death.

AIDS-Related Opportunistic Infections↗

[Hepatic abscesses in childhood: retrospective study about 33 cases observed in New-Caledonia between 1985 and 2003].

UNLABELLED: Hepatic abscesses in childhood are rarely observed in Europe. The aim of this word was to study how to diagnose and how to treat an hepatic abscess. METHODS: Between 1985 and 2003, we recensed retrospectively 33 cases of hepatic abscesses hospitalised in the paediatric unit of Noumea. RESULTS: Children were mainly melanesians (79%), 7 years old on average, having abdominal pains, a clinical and biological infectious syndrome, and abscesses images on ultrasonography or computed tomography. The identified micro-organisms included Entamoeba histolytica in 30% (10 cases); Staphylococcus aureus in 15% (five cases), Staphylococcus coagulase negative in 6% (two cases), Streptococcus D in 3% (one case); Bartonella henselae in 9% (three cases); ascaris in 6% (two cases); Mycobacterium tuberculosis in 6% (two cases). In eight cases no bacteria was identified (24%) but the good evolution after antibiotics and the negative amoebic serology looked like pyogenic abscesses. Two abscesses were aspirated, two were drained, one child had a surgical intervention. There was no death. Following a mean duration of 1 month for antibiotics treatment, outcome was always favourable. CONCLUSION: Diagnosis of hepatic abscess can be difficult. Ultrasonography shows the abscess but not the causal agent. The amoebic serology is sensible, consequently, its negativity leads to evoke a pyogenic agent. Early antibiotic treatment against pyogenic, anaerobic bacteria, and Entamoeba histolytica is required. Hepatic abscesses in ascaridiosis, tuberculosis and cat-scratch disease are less frequently encountered. If diagnosis remains doubtful or clinical evolution worsens, or if abscess volume increases, a percutaneous aspiration or drainage is needed.

Child↗

[Sudden sight impairment revealing a cat-scratch disease: report of three cases].

UNLABELLED: Cat-scratch disease is a frequent but innocuous cause of chronic lymphadenopathy in children. Numerous atypical forms have been described. We report three cases of acute sight impairment revealing a cat-scratch disease. BACKGROUND: A 13 year-old boy and two girls aged 10 and 13 suffered from a sudden bilateral sight impairment with papillary edema, with fever in two cases. Neurological examinations, X-rays and lumbar puncture results were found normal. However, all patients were tested positive to Bartonella Henselae. Antibiotic and anti-inflammatory treatments were efficient in two cases. CONCLUSION: Cat-scratch disease can be characterized by an isolated and acute sight impairment with a stellate neuroretinitis. The potency of antibiotic treatments is debatable.

Adolescent↗

Latent infective endocarditis: epidemiology and clinical characteristics of patients with unsuspected endocarditis detected after elective valve replacement.

BACKGROUND: The diagnosis of infective endocarditis is usually made on the basis of clinical and laboratory criteria and may be confirmed by histologic examination or culture of excised valves. We tried to determine the incidence and significance of inflammatory changes in valves excised during operations for reasons other than infective endocarditis. METHODS: The charts and histopathology of all patients undergoing valve replacement during a 10-year period (1993-2002) were reviewed. A total of 868 patients underwent a total of 970 valve replacements during this period, of whom 11 patients (1.3%) were for endocarditis, with the remaining 857 (98.7%) for other indications. All excised valves were cultured and examined histologically for the presence of inflammatory infiltrates, vegetations, and microorganisms. RESULTS: In 8 of 857 patients (0.9%), the histologic examination unexpectedly demonstrated an infiltrate suggestive of endocarditis. Blood and valve cultures, and serologic tests for Mycoplasma, Chlamydia, Legionella, Q fever, Brucella, Rickettsiae, VDRL, and Bartonella were negative in all but 1 patient, who was found to have Q fever. All received a prolonged course of antibiotics. Six patients had an uneventful recovery; 1 had intramyocardial abscesses and expired during cardiac reoperation; and 1 had recurrent fever and dehiscence of the aortic and mitral valve prostheses and after two cardiac reoperations remains in severe heart failure. CONCLUSIONS: The presence of an unexpected inflammatory infiltrate in heart valves excised for reasons other than endocarditis may occur in 0.9% of such operations; these infiltrates could indicate presence of endocarditis. A microbial origin should be sought, and patients should receive empiric antibiotic treatment for endocarditis.

Adolescent↗

Cat scratch disease encephalopathy in an immunocompetent patient.

Cat scratch disease (CSD) is typically a self-limited regional lymphadenopathy in children and young adults that is caused by Bartonella henselae. The majority of CSD cases resolve spontaneously; however, many systemic complications have been described. We report an unusual case of CSD presenting as an epitrochlear arm mass and complicated by encephalopathy. Identification of B. henselae DNA in the affected lymph node and cerebrospinal fluid confirmed the diagnosis of CSD. Systemic antibiotic therapy was administered and the patient improved without any neurological deficit.

Journal Article↗

Purification of the YadA membrane anchor for secondary structure analysis and crystallization.

Non-fimbrial adhesins, such as Yersinia YadA, Moraxella UspA1 and A2, Haemophilus Hia and Hsf, or Bartonella BadA, represent an important class of molecules by which pathogenic proteobacteria adhere to their hosts. They form trimeric surface structures with a head-rod-anchor architecture. Whereas their head and rod domains may be of heterologous origin, their anchor domains are homologous and display the properties of autotransporters. Conflicting topology models exist for these membrane anchors. Here, we describe the expression and purification of the membrane anchor of YadA from Yersinia enterocolitica for structural biology experiments. We expressed YadA-M in the Escherichia coli outer membrane. After solubilization and purification, it is a trimer of extreme stability. Using protein FTIR and secondary structure analysis, we show that the anchor is a beta-barrel, but contains a helical part at its N-terminus. We have crystallized the protein under various conditions and present X-ray data to 3.8 A resolution.

Adhesins, Bacterial↗

DNA examination of ancient dental pulp incriminates typhoid fever as a probable cause of the Plague of Athens.

BACKGROUND: Until now, in the absence of direct microbiological evidence, the cause of the Plague of Athens has remained a matter of debate among scientists who have relied exclusively on Thucydides' narrations to introduce several possible diagnoses. A mass burial pit, unearthed in the Kerameikos ancient cemetery of Athens and dated back to the time of the plague outbreak (around 430 BC), has provided the required skeletal material for the investigation of ancient microbial DNA. OBJECTIVE: To determine the probable cause of the Plague of Athens. METHOD: Dental pulp was our material of choice, since it has been proved to be an ideal DNA source of ancient septicemic microorganisms through its good vascularization, durability and natural sterility. RESULTS: Six DNA amplifications targeted at genomic parts of the agents of plague (Yersinia pestis), typhus (Rickettsia prowazekii), anthrax (Bacillus anthracis), tuberculosis (Mycobacterium tuberculosis), cowpox (cowpox virus) and cat-scratch disease (Bartonella henselae) failed to yield any product in 'suicide' reactions of DNA samples isolated from three ancient teeth. On the seventh such attempt, DNA sequences of Salmonella enterica serovar Typhi were identified providing clear evidence for the presence of that microorganism in the dental pulp of teeth recovered from the Kerameikos mass grave. CONCLUSION: The results of this study clearly implicate typhoid fever as a probable cause of the Plague of Athens.

DNA, Bacterial↗