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Dietrich W Büttner

Publications and source records attributed to Dietrich W Büttner.

At least 19 recordsLinked to original sources
PubMed2006

The filarial parasite Onchocerca volvulus generates the lipid mediator prostaglandin E(2).

Prostaglandins exhibit regulatory effects on the vascular and immune system. Prostaglandin E(2) (PGE(2)) modulates T helper (Th) cell and effector cell functional reactivity, thereby promoting Th2 responses. We found significant expression of PGE(2) in male and female Onchocerca volvulus. Using immunohistology, PGE(2) was predominantly detected in the hypodermis of adult O. volvulus, the metabolically most active tissue of the filaria. In contrast, the muscles were PGE(2)-negative and the epithelia of intestine and uterus and male genital tract showed only weak staining. Oocytes were well labeled whereas embryos and sperms did not react. Less pronounced PGE(2) staining was observed in some dermal microfilariae. The expression of PGE(2) was found independent of antifilarial (ivermectin) as well as anti-endobacterial (doxycycline) treatment of O. volvulus-infected patients. PGE(2) was also demonstrated in extracts of adult worms by high-performance liquid chromatography-mass spectrometry. Release of PGE(2) from live or moribund filariae can affect the host s metabolism and immune response in favor of the filarial parasite.

Animals↗
PubMed2006

Subcutaneous Taenia crassiceps infection in a patient with non-Hodgkin's lymphoma.

Infections with larvae of Taenia crassiceps are rare in humans and have mostly affected patients with acquired immunodeficiency syndrome. We report the first case of a patient with malignancy (non-Hodgkin's lymphoma) and infection of the subcutis and muscles of the hand and forearm. Surgery and antiparasitic chemotherapy led to a complete cure.

Aged, 80 and over↗
PubMed2005

Cloning, characterization and DNA immunization of an Onchocerca volvulus glyceraldehyde-3-phosphate dehydrogenase (Ov-GAPDH).

In the search for Onchocerca volvulus antigens possibly involved in protection against human onchocerciasis, partial amino acid sequence analysis of one of the O. volvulus antigens of the serologically identified proteins showed a close relationship to the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) protein family. Subsequent adult worm cDNA library screening and cloning produced a clone of 1650 bp. An open reading frame spans over 1020 bp encoding for a protein of 340 amino acids with an apparent molecular weight of 38000. Comparison of the complete amino acid sequence identified this protein as a member of the GAPDH protein family. The recombinantly expressed protein shows GAPDH enzymatic activity as well as plasminogen-binding capacity. DNA sequence analysis of the corresponding gene revealed the presence of two introns. Using immunohistology Ov-GAPDH was observed in microfilariae, infective larvae, and adult male and female worms. Most striking was the labelling of the musculature of the body wall. Labelling was also observed in the pseudocoeloma cavity and in a subset of cell nuclei, suggesting additional, non-glycolytic functions of the Ov-GAPDH. Gene gun immunization with the DNA-construct in cattle led to specific humoral immune responses. Thus, the protective potential of the DNA-construct of Ov-GAPDH can be evaluated in vaccination trials using animal models such as the cattle/Onchocerca ochengi model.

Amino Acid Sequence↗
PubMed2004

The major surface protein of Wolbachia endosymbionts in filarial nematodes elicits immune responses through TLR2 and TLR4.

More than 150 million humans in tropical countries are infected by filarial nematodes which harbor intracellular bacterial endosymbionts of the genus Wolbachia (Rickettsiales). These bacteria have been implicated in adverse effects of drug treatment in filariasis. The present study provides evidence that purified major Wolbachia surface protein (rWSP) acts as an inducer of the innate immune system through TLR2 and TLR4: 1) recombinant, stringently purified rWSP elicited the release of TNF-alpha, IL-12, and IL-8 from cultured blood cells of both Onchocerca volvulus-infected and uninfected people; 2) the inflammatory response to rWSP challenge was TLR2- and TLR4-dependent as demonstrated with TLR-transfected fibroblastoid cells, as well as macrophages and dendritic cells from functional TLR-deficient mice; 3) blood cells of onchocerciasis patients exposed to rWSP also generated down-regulating mediators IL-10 and PGE(2) after 6 days of culture; 4) furthermore, rWSP-reactive IgG1 Abs were present in sera of O. volvulus-infected people but not in those of uninfected Europeans. The lack of rWSP-reactive IgE and IgG4 in serum indicated a bias toward a Th1-type adaptive immune response. Abs against rWSP stained endobacteria in living and degenerating adult O. volvulus filariae, tissue microfilariae and host tissue macrophages that apparently had engulfed microfilariae. Thus, filarial helminths, through products of their endobacteria such as WSP, acquire characteristics of a typical microbial pathogen inducing immune responses via TLR2 and TLR4.

Adolescent↗
PubMed2004

Wolbachia endosymbionts of Onchocerca volvulus express a putative periplasmic HtrA-type serine protease.

Wolbachia are intracellular bacteria of many filarial nematodes. A mutualistic interaction between the endobacteria and the filarial host is likely, because the clearance of Wolbachia by tetracycline leads to the obstruction of embryogenesis and larval development. Databases were searched for exported molecules to identify candidates involved in this mutualism. Fragments of a Wolbachia serine protease from the human filarial parasite Onchocerca volvulus were obtained (Wol-Ov-HtrA) by the use of a PCR technique and primers based on the Rickettsia prowazekii genome. The deduced amino acid sequence exhibited 87% and 81% identity to the homologous Wolbachia proteases identified from Brugia malayi and Drosophila melanogaster, respectively. The full-length cDNA encodes 494 amino acids with a calculated mass of 54 kDa. Three characteristic features, (i) a catalytic triad of serine proteases, (ii) two PDZ domains and (iii) a putative signal peptide, classify the endobacterial protein as a member of the periplasmic HtrA family of proteases known to express chaperone and regulator activity of apoptosis. Using a rabbit antiserum raised against a recombinantly expressed 33-kDa fragment of Wol-Ov-HtrA, strong labelling of the antigen was found associated with endobacteria in hypodermis, oocytes, zygotes, all embryonic stages and microfilariae of O. volvulus. Staining of hypodermal cytoplasm surrounding the endobacteria indicated a possible release of the protein from the Wolbachia. The demonstration of Wol-Ov-HtrA-reactive IgG1 antibodies in sera of O. volvulus-infected persons indicated the exposure to the protein and its recognition by the human immune system. Wol-Ov-HtrA is a candidate for an exported Wolbachia protein that may interact with the filarial host metabolism.

Amino Acid Sequence↗
PubMed2004

The impact of ivermectin treatment alone and when in parallel with Simulium neavei elimination on onchocerciasis in Uganda.

The study was conducted in August 2002 in Kigoyera parish in Kyenjojo district, where ivermectin treatment had been the strategy to control onchocerciasis since 1991 and was later supplemented with Simulium neavei control in 1995 and subsequent elimination; and in July 2003 in Kicece parish in Kamwenge district, where ivermectin treatment alone had been the strategy used to control onchocerciasis since 1991. Our objective was to examine and compare the impact of ivermectin treatment alone and when in parallel with S. neavei elimination on nodule and microfilariae carrier rates and on onchocercal dermatitis to provide baseline data that could be used to monitor the trends of microfilariae carrier rates for decision-making on when to discontinue ivermectin treatment. The combined interventions had significantly reduced onchocercal dermatitis from 34% pre-control to 2.9% (P < 0.001), microfilariae carrier rate from 88 to 7.5% (P < 0.001) and nodule prevalence from 49 to 19.2% (P < 0.001). Ivermectin treatment alone had also reduced onchocercal dermatitis prevalence from 34.2% pre-control to 9.5% (P < 0.001), the microfilariae carrier rate from 78 to 27.8% (P < 0.001) and nodule prevalence from 49.1 to 14.2% (P < 0.001). None of the children under 10 years were nodule or microfilariae carriers in both study areas. Histological examination of eight nodules extirpated from patients in Kigoyera identified five male and 12 female adult worms that were all old and alive. Five live and one dead female worms and one live male worm were identified from nodules extirpated from patients in Kicece. There was no female worm with embryogenesis from the nodules obtained from Kigoyera while two female worms from five nodules obtained from Kicece still showed a few embryos. Two female worms in each of the study area had sperms in uteri indicating that male worms were still active. Ivermectin treatment in parallel with vector elimination had a greater impact on onchocercal dermatitis and microfilariae carrier rates than ivermectin treatment alone. It would be worthwhile considering supplementation of ivermectin treatment with vector elimination in all isolated foci with S. neavei transmission to hasten the elimination of onchocerciasis as a public health and socio-economic problem in those foci.

Adolescent↗
PubMed2003

Molecular cloning of an alpha-enolase from the human filarial parasite Onchocerca volvulus that binds human plasminogen.

Enolase represents a multifunctional protein involved in basic energy metabolism and plasminogen binding and activation at the surface of prokaryotic pathogens. A complete cDNA of 1615 bp of an alpha-enolase from Onchocerca volvulus (Ov-ENO) was isolated using a PCR-based approach. The open reading frame encoded for 435 amino acids and the high degree of conservation included the crucial amino acid residues that participate in the formation of the catalytic site, Mg(2+) binding site, and a hydrophobic motif reported to relate to surface expression. A 1089-bp fragment was expressed in a N-terminal 6 x His-tag expression vector in Escherichia coli. By immunohistological analysis using anti-Ov-ENO rabbit antibodies, native enolase could be detected in most tissues of adult O. volvulus, microfilariae, and infective larvae. Intense staining was observed in the muscles, where the energy consumption is high. The purified recombinant protein fragment revealed plasminogen binding activity in a blot-overlay assay employing anti-plasminogen antibodies. In sera from individuals infected with O. volvulus, IgG antibodies reactive with recombinant Ov-ENO were demonstrated by immunoblot and enzyme-linked immunosorbent analyses. The plasminogen-binding property of O. volvulus alpha-enolase may support plasmin-mediated proteolysis including degradation of host's extracellular matrix thereby promoting the migration of larval stages through tissues. The recognition by antibodies in sera of O. volvulus-infected persons indicate an involvement of the protein in the interaction between the parasite and the human host.

Amino Acid Sequence↗
PubMed2003

Obligatory symbiotic Wolbachia endobacteria are absent from Loa loa.

BACKGROUND: Many filarial nematodes harbour Wolbachia endobacteria. These endobacteria are transmitted vertically from one generation to the next. In several filarial species that have been studied to date they are obligatory symbionts of their hosts. Elimination of the endobacteria by antibiotics interrupts the embryogenesis and hence the production of microfilariae. The medical implication of this being that the use of doxycycline for the treatment of human onchocerciasis and bancroftian filariasis leads to elimination of the Wolbachia and hence sterilisation of the female worms. Wolbachia play a role in the immunopathology of patients and may contribute to side effects seen after antifilarial chemotherapy. In several studies Wolbachia were not observed in Loa loa. Since these results have been doubted, and because of the medical significance, several independent methods were applied to search for Wolbachia in L. loa. METHODS: Loa loa and Onchocerca volvulus were studied by electron microscopy, histology with silver staining, and immunohistology using antibodies against WSP, Wolbachia aspartate aminotransferase, and heat shock protein 60. The results achieved with L. loa and O. volvulus were compared. Searching for Wolbachia, genes were amplified by PCR coding for the bacterial 16S rDNA, the FTSZ cell division protein, and WSP. RESULTS: No Wolbachia endobacteria were discovered by immunohistology in 13 male and 14 female L. loa worms and in numerous L. loa microfilariae. In contrast, endobacteria were found in large numbers in O. volvulus and 14 other filaria species. No intracellular bacteria were seen in electron micrographs of oocytes and young morulae of L. loa in contrast to O. volvulus. In agreement with these results, Wolbachia DNA was not detected by PCR in three male and six female L. loa worms and in two microfilariae samples of L. loa. CONCLUSIONS: Loa loa do not harbour obligatory symbiotic Wolbachia endobacteria in essential numbers to enable their efficient vertical transmission or to play a role in production of microfilariae. Exclusively, the filariae cause the immunopathology of loiasis is patients and the adverse side effects after antifilarial chemotherapy. Doxycycline cannot be used to cure loiais but it probably does not represent a risk for L. loa patients when administered to patients with co-infections of onchocerciasis.

Journal Article↗
PubMed2003

Isolation and characterization of the regulatory subunit of cAMP-dependent protein kinase from the filarial parasite Onchocerca volvulus.

Protein kinases exert major regulatory effects in eukaryotic signaling events. As these proteins play central regulatory and sensory functions they are interesting targets for antiparasitic drug development and serve as vaccine candidates. A cDNA with an open reading frame of 1122 bp coding for the regulatory subunit of the cAMP-dependent protein kinase (Ov-pka-r) of the pathogenic human nematode Onchocerca volvulus has been isolated. The predicted protein displays 84% homology to the corresponding protein of Caenorhabditis elegans and 71% to the human homologue. The O. volvulus protein has unique features, it includes six cysteine residues, as compared to four residues in mammals. Ov-PKA-r was recombinantly expressed as His-tagged protein and under reducing conditions showed a molecular mass of 52 kDa. In sera from O. volvulus patients IgG antibodies were found that strongly reacted with the recombinant Ov-PKA-r. Using rabbit antisera raised against the recombinant protein for immunohistology allowed the localization of the native Ov-PKA-r within the nervous system and sensory organs of adult O. volvulus worms and of microfilariae. The predominant expression in the nervous system and sensory organs as well as the unique structural features identify this signaling molecule of O. volvulus as a new and interesting target for drug or vaccine development.

Amino Acid Sequence↗
PubMed2003

Doxycycline as a novel strategy against bancroftian filariasis-depletion of Wolbachia endosymbionts from Wuchereria bancrofti and stop of microfilaria production.

Chemotherapy of onchocerciasis by doxycycline, which targets symbiotic Wolbachia endobacteria, has been shown to result in a long-term sterility of adult female worms and corresponding absence of microfilariae. It represents an additional chemotherapeutic approach. The aim of this study was to determine whether a similar regimen would also show efficacy against Wuchereria bancrofti. Ghanaian individuals ( n=93) with lymphatic filariasis and a minimum microfilaremia of 40 microfilariae/ml were included in a treatment study consisting of four arms: (1) doxycycline 200 mg/day for 6 weeks; (2) doxycycline as in (1), followed by a single dose of ivermectin after 4 months; (3) ivermectin only; or (4) no treatment during observation period of 1 year (ivermectin at the end of the study). Doxycycline treatment resulted in a 96% loss of Wolbachia, as determined by real time PCR from microfilariae. After 12 months, doxycycline had led to a 99% reduction of microfilaremia when given alone, and to a complete amicrofilaremia together with ivermectin. In contrast, after ivermectin treatment alone a significant presence of microfilariae remained (9% compared to pretreatment), as known from other studies. This study shows that doxycycline is also effective in depleting Wolbachia from W. bancrofti. It is likely that the mechanism of doxycycline is similar to that in other filarial species, i.e., a predominant blockade of embryogenesis, leading to a decline of microfilariae according to their half-life. This could render doxycycline treatment an additional tool for the treatment of microfilaria-associated diseases in bancroftian filariasis, such as tropical pulmonary eosinophilia and microfiluria.

Adolescent↗
PubMed2003

An aspartate aminotransferase of Wolbachia endobacteria from Onchocerca volvulus is recognized by IgG1 antibodies from residents of endemic areas.

Wolbachia are intracellular alpha-proteobacteria, closely related to Rickettsia, that infect various arthropods and filarial parasites. In the present study, the cDNA encoding the aspartate aminotransferase (AspAT) of Wolbachia from the human pathogenic filarial parasite Onchocerca volvulus (Ov-WolAspAT) was identified. At the amino acid level, the identity of the Ov-WolAspAT was 56% to Rickettsia prowazekii AspAT and 54% to the AspAT of the nitrogen-fixing bacterium Sinorhizobium meliloti, but the highest degree of identity was found to the putative AspAT of Wolbachia from Brugia malayi and Drosophila melanogaster (85%). All of these bacterial AspATs are members of the AspAT subclass Ib. A 35 kDa fragment of the Ov-WolAspAT was expressed in Escherichia coli, and immunolocalization using polyclonal antibodies against this antigen revealed that Ov-WolAspAT is present in a considerable proportion of the Wolbachia from O. volvulus, as well as in the endobacteria of several other filarial parasites. Western blot analysis using recombinant Ov-WolAspAT as antigen showed that IgG1 antibodies were present in 70 (51%) individuals living in areas endemic for O. volvulus, B. malayi or Wuchereria bancrofti and no IgG4 or IgE antibodies were found. Among 40 sera of persons from Uganda and Liberia who were putatively not infected with human filarial parasites, 11 (28%) individuals presented IgG1 antibodies, while none of the 33 sera from healthy Europeans and none of the 14 sera from patients with proven Rickettsia or Brucella infections reacted with the antigen. These results also show that an intracellular protein of Wolbachia endobacteria (WolAspAT) acts as antigen in human filariasis.

Amino Acid Sequence↗
PubMed2003

Onchocerciasis.

Explore the source record for details and available documents.

Animals↗
PubMed2003

Doxycycline in the treatment of human onchocerciasis: Kinetics of Wolbachia endobacteria reduction and of inhibition of embryogenesis in female Onchocerca worms.

Recently, experts have warned that mass treatment with ivermectin alone may not interrupt the transmission of Onchocerca. Hence, additional drugs are needed, such as antibiotics acting on symbiotic endobacteria of the filariae, the causative agents of onchocerciasis. Based on animal experiments, human onchocerciasis was treated with doxycycline, and preliminary observations published in 2001 in The Lancet showed sterility in female worms by depletion and marked reduction in symbiotic Wolbachia endobacteria from the filariae. Here, a detailed kinetic analysis of the features of the worms, following administration or not of doxycycline to the patients is reported. Sixty-three onchocerciasis patients in Ghana were treated with 100 mg doxycycline daily for 6 weeks and 2 or 6 months later with ivermectin. Onchocercomas were extirpated 2, 6, 11 and 18 months after the onset of treatment and the filariae were examined by immunohistology and PCR. The analysis showed: (i) progressive depletion of Wolbachia from adult worms and microfilariae by doxycycline over a period of 6 months; (ii) inhibition of embryogenesis by doxycycline after 6 months with respect to all embryo stages followed by decline in microfilariae after 11 months; (iii) reduction in spermatozoa in the female genital tract by doxycycline, whereas spermiogenesis was only partly reduced after 11 and 18 months; (iv) no relevant macro- or microfilaricidal activity; (v) depletion/marked reduction in endobacteria and inhibition of embryogenesis were sustained until 18 months after doxycycline and 12 months after co-administration of ivermectin; (vi) no severe adverse side effects were seen. Due to its long-lasting inhibition of embryogenesis, doxycycline presents an additional strategy for the treatment of onchocerciasis and control of Onchocerca microfilariae transmission. Extension of the existing registration will not require much time or high cost. Treatment of individual patients can be considered immediately.

Animals↗
PubMed2003

Adverse reactions to ivermectin treatment in Simulium neavei-transmitted onchocerciasis.

To assess adverse effects of ivermectin treatment in a Simulium neavei-transmitted focus of onchocerciasis, a study was conducted with 1,246 patients infected with Onchocerca volvulus in eight villages in western Uganda. Study participants were treated the first time with a single dose of 150 microg/kg of ivermectin. Adverse reactions to ivermectin were determined through questioning and clinical examination during house-to-house visits to the participants within 48 hours after ivermectin treatment. Overall adverse reactions were observed in 737 (59.1%) patients. Severe reactions were rare (10 patients, 1.4%). Our data show that adverse reactions to ivermectin in an S. neavei-transmitted onchocerciasis focus in western Uganda occur frequently. In spite of the fact that many patients showed adverse reactions to ivermectin, the drug was well accepted and appreciated by the population.

Adolescent↗
PubMed2002

Onchocerca volvulus-exposed persons fail to produce interferon-gamma in response to O. volvulus antigen but mount proliferative responses with interleukin-5 and IL-13 production that decrease with increasing microfilarial density.

The cellular immune response to Onchocerca volvulus antigen (OvAg) was studied in 551 persons exposed to O. volvulus transmission in a hyperendemic area of Ghana, West Africa. A whole-blood assay showed that, in response to a soluble O. volvulus extract, cell proliferation, as well as interleukin (IL)-5 and IL-13 concentrations in the supernatants, were high in cultures of blood from microfilaria (mf)-negative persons and significantly decreased with increasing mf counts of the donors. Only background concentrations of interferon (IFN)-gamma were found, and these did not correlate with mf counts. In response to a mitogen, cells from all persons strongly reacted with proliferation and secretion of all 3 cytokines studied. These findings show that the response of human peripheral blood cells to OvAg does not include significant IFN-gamma production; that mf negativity is associated with IL-5 and IL-13 production but not, as previously suggested, with IFN-gamma production; and that IL-5 and IL-13 production decreases with increasing mf density.

Adolescent↗
PubMed2002

Antibiotics for the treatment of onchocerciasis and other filarial infections.

More effective drugs are needed for the treatment of human filarial diseases and the elimination of these infections as a public health problem. The drugs must either kill or sterilize adult worms. The relevant filariae, Onchocerca volvulus, Wuchereria bancofti and Brugia species, harbor rickettsial endoboacteria of the genus Wolbachia as symbionts. Animal experiments have shown that the elimination of these endobacteria causes inhibition of embryogenesis, and with Onchocerca ochengi a macrofilaricidal effect. Trials with human onchocerciasis patients using doxycydine demonstrated a long-term sterilizing activity, opening up a new strategy for the control of filarial infections. Indications of antiwolbachial therapy against onchocerciasis are discussed.

Animals↗
PubMedDate not supplied

Onchocerca volvulus: expression and immunolocalization of a nematode cathepsin D-like lysosomal aspartic protease.

The N-terminal region of the cathepsin D-like aspartic protease from the human filarial parasite Onchocerca volvulus was expressed as His-tag fusion protein. Light and electron microscopic immunohistology using antibodies against the recombinant protein showed labeling of lysosomes in the hypodermis and epithelia of the intestine and the reproductive organs of Onchocerca. While developing oocytes were negative, mature oocytes and early morulae showed strong labeling. In older embryos and mature microfilariae, stained lysosomes were only found in a few cells. Cell death in degenerating microfilariae of patients untreated and treated with microfilaricidal drugs was associated with strong expression of aspartic protease. IgG1, IgG4, and IgE antibodies reactive with the recombinant protein were demonstrated in sera from onchocerciasis patients indicating exposure and recognition of the enzyme by the host's defence system. The aspartic protease of O. volvulus appears to function in intestinal digestion and tissue degradation of the filaria.

Animals↗