Rickettsia typhi infection with interstitial pneumonia in a traveler treated with moxifloxacin.

Rickettsial diseases may play an important part in the differential diagnosis of fever in returned travelers. The initial empirical treatment needs to take Rickettsia species into consideration to avoid the development of life-threatening courses. Here, we present a case of interstitial pneumonia associated with Rickettsia typhi infection treated with moxifloxacin.

Eotaxin-3 in Churg-Strauss syndrome: a clinical and immunogenetic study.

OBJECTIVES: To determine the potential of eotaxin-3 as a diagnostic marker for active disease and genetic susceptibility factor for Churg-Strauss syndrome (CSS). METHODS: A total of 37 patients with active, relapsed or inactive CSS, 123 healthy controls and 138 disease controls were studied. Clinical data were collected and serum levels of eotaxin-3 were determined. Ex vivo stability of eotaxin-3 in serum samples was tested. Furthermore, the association of single nucleotide polymorphisms (SNPs) in the eotaxin-3 gene with CSS was determined in 161 CSS patients and 124 healthy controls. RESULTS: Serum eotaxin-3 was highly elevated in active CSS patients. Neither eosinophilic diseases nor other small-vessel vasculitides were associated with high serum eotaxin-3 levels. Receiver operating characteristic curve analysis determined a sensitivity and specificity of 87.5 and 98.6% at a cut-off level of 80 pg/ml. None of the tested SNPs within the eotaxin-3 gene influenced the susceptibility to develop CSS. CONCLUSIONS: Serum eotaxin-3 is a sensitive and specific marker for the diagnosis of active CSS suitable for routine clinical practice. Previously described SNPs in the eotaxin-3 gene do not predict the risk of developing CSS.

Dirofilaria repens infection and concomitant meningoencephalitis.

Dirofilaria repens, a filarial nematode of dogs and other carnivores, can accidentally infect humans. Clinical symptoms are usually restricted to a subcutaneous nodule containing a single infertile parasite. Here, we report a case of D. repens infection with a subcutaneous gravid worm and the patient's concomitant meningoencephalitis and aphasia.

Epidemiological and Ecological Characterization of the EHEC O104:H4 Outbreak in Hamburg, Germany, 2011.

In 2011, a large outbreak of entero-hemorrhagic E. coli (EHEC) and hemolytic uremic syndrome (HUS) occurred in Germany. The City of Hamburg was the first focus of the epidemic and had the highest incidences among all 16 Federal States of Germany. In this article, we present epidemiological characteristics of the Hamburg notification data. Evaluating the epicurves retrospectively, we found that the first epidemiological signal of the outbreak, which was in form of a HUS case cluster, was received by local health authorities when already 99 EHEC and 48 HUS patients had experienced their first symptoms. However, only two EHEC and seven HUS patients had been notified. Middle-aged women had the highest risk for contracting the infection in Hamburg. Furthermore, we studied timeliness of case notification in the course of the outbreak. To analyze the spatial distribution of EHEC/HUS incidences in 100 districts of Hamburg, we mapped cases' residential addresses using geographic information software. We then conducted an ecological study in order to find a statistical model identifying associations between local socio-economic factors and EHEC/HUS incidences in the epidemic. We employed a Bayesian Poisson model with covariates characterizing the Hamburg districts as well as incorporating structured and unstructured spatial effects. The Deviance Information Criterion was used for stepwise variable selection. We applied different modeling approaches by using primary data, transformed data, and preselected subsets of transformed data in order to identify socio-economic factors characterizing districts where EHEC/HUS outbreak cases had their residence.

Human African trypanosomiasis with 7-year incubation period: clinical, laboratory and neuroimaging findings.

Human African trypanosomiasis (HAT), also referred to as "sleeping sickness", is caused by the parasite Trypanosoma brucei. Diagnosing imported HAT outside endemic areas is difficult and diagnosis is often delayed. We report a case of imported human African trypanosomiasis caused by Trypanosoma brucei gambiense with an unusually long incubation period of at least 7 years. A 33 year old male African patient, a former resident of Cameroon, presented with a 4-month history of progressive personality changes. A few weeks before presentation the patient had first been admitted to a psychiatric ward and received antidepressant treatment, until a lumbar puncture showed pleocytosis and then antibiotic treatment for suspected neuroborreliosis was initiated. The patient continued to deteriorate during antibiotic treatment and became increasingly lethargic. Under antiparasitic and anti-inflammatory treatment, the condition of the patient gradually improved over the following months and he recovered completely after 24 months of follow-up. This well-documented case illustrates typical difficulties in establishing the correct diagnosis outside endemic areas and provides an overview of typical clinical, neuropathological and neuroimaging findings in T. b. gambiense trypanosomiasis, guiding the clinician in establishing the correct diagnosis in this rare disease.

Ito cells are liver-resident antigen-presenting cells for activating T cell responses.

Here we identified Ito cells (hepatic stellate cells, HSC), known for storage of vitamin A and participation in hepatic fibrosis, as professional liver-resident antigen-presenting cells (APC). Ito cells efficiently presented antigens to CD1-, major histocompatibility complex (MHC)-I-, and MHC-II-restricted T cells. Ito cells presented lipid antigens to CD1-restricted T lymphocytes such as natural killer T (NKT) cells and promoted homeostatic proliferation of liver NKT cells through interleukin-15. Moreover, Ito cells presented antigenic peptides to CD8(+) and CD4(+) T cells and mediated crosspriming of CD8(+) T cells. Peptide-specific T cells were activated by transgenic Ito cells presenting endogenous neoantigen. Upon bacterial infection, Ito cells elicited antigen-specific T cells and mediated protection. In contrast to other liver cell types that have been implicated in induction of immunological tolerance, our data identify Ito cells as professional intrahepatic APCs activating T cells and eliciting a multitude of T cell responses specific for protein and lipid antigens.

The molecular basis for hereditary porcine membranoproliferative glomerulonephritis type II: point mutations in the factor H coding sequence block protein secretion.

Porcine membranoproliferative glomerulonephritis type II in piglets of the Norwegian Yorkshire breed is considered the first animal model of human dense deposit disease. Porcine dense deposit disease is caused by the absence of the complement regulator factor H in plasma. Here we report the molecular basis for this absence. Single nucleotide exchanges at position C1590G and T3610G in the coding region of the factor H gene result in amino acid exchanges at nonframework residues L493V and I1166R that are located within SCR 9 and SCR 20, respectively. Apparently the L493V mutation represents a polymorphism whereas the I1166R causes the physiological consequences a block in protein secretion. Expression analysis shows comparable mRNA levels for factor H in liver tissue derived from both affected and healthy animals. In affected piglets, factor H protein is detected in increased amounts in liver cells. Factor H accumulates inside the hepatocytes and is not released as shown by Western blot analysis and immunohistochemistry. These data demonstrate that single amino acid exchanges of two nonframework amino acids either alone or in combination block protein secretion of factor H. This observation is also of interest for other human diseases in which factor H is involved, such as human factor H-associated form of hemolytic uremic syndrome.

Pig complement regulator factor H: molecular cloning and functional characterization.

Complement is an efficient defense mechanism of innate immunity. Factor H is the central complement regulator of the alternative pathway, acting in the fluid-phase and on self surfaces. Pigs are considered a suitable source for xenotransplantation and thus several membrane-bound pig complement regulators with importance for the acute rejection phase have been investigated. However, pig fluid-phase regulators have not been described so far. We report the cloning, expression and functional characterization of pig factor H. After constructing a pig liver cDNA library, a full-length factor H cDNA was isolated and sequenced. The predicted protein is organized in 20 short consensus repeat (SCR) domains and has an overall identity of 62% to the human protein. For functional characterization, three deletion constructs of pig factor H were expressed in insect cells. Pig factor H construct SCR 1-4 has cofactor activity for factor I-mediated cleavage of human C3b, which is similar to the human regulator. In addition, this N-terminal construct binds to human C3b, while a construct consisting of SCR 15-20 showed a weaker binding to human C3b/C3d. Pig factor H has two major binding sites for heparin, as the two constructs representing SCR 1-7 and SCR 15-20 proteins, but not the SCR 1-4 protein, bind heparin. The C-terminal construct is able to bind to human endothelial cells, as assayed by FACS. We show that pig and human factor H share functional characteristics in complement regulation and cell surface binding. Possible consequences of using pig livers for xenotransplantation are discussed.