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D W Buttner

Publications and source records attributed to D W Buttner.

10 recordsLinked to original sources

Cutaneous pathology in onchocerciasis associated with pronounced systemic T-helper 2-type responses to Onchocerca volvulus.

BACKGROUND: Of 18 million people world-wide who are infested with the tissue nematode Onchocerca volvulus, more than 30% are considered to have skin lesions, the pathomechanisms of which are poorly understood. OBJECTIVES: To relate skin changes associated with onchocerciasis to parasitological findings and systemic cellular immune responses. METHODS: In the course of a genetic study, 691 members of 241 families exposed to hyperendemic O. volvulus transmission and free of other filarial or schistosomal infestations were studied clinically, by counting palpable Onchocerca nodules and skin microfilariae, by measuring peripheral blood cell (PBC) counts and total serum IgE, and by determining PBC in vitro proliferation and cytokine secretion in response to O. volvulus antigen. RESULTS: Of 691 individuals studied, 219 presented with onchocerciasis-associated skin changes. The groups of individuals with and without skin lesions neither differed in prevalences nor in average numbers of microfilariae. Compared with individuals without skin lesions, pronounced systemic T-helper (Th) 2-type responses were found with a trend of increasing intensity in the order of depigmentation, papular dermatitis, atrophy and lichenified dermatitis. Differences between the groups were most pronounced for serum IgE, less so for eosinophilia, and relatively weak for PBC proliferation and interleukin-5 secretion. CONCLUSIONS: Skin lesions in onchocerciasis are associated with a spectrum of increasing generalized Th2-type responses ranging from low reactivities in cases of depigmentation alone to strong reactivities in cases of lichenification.

Adolescent↗

A stochastic model for the aggregation of Onchocerca volvulus in nodules.

A model is presented which describes the aggregation of female Onchocerca volvulus in nodules and their distribution in the human population. The basic model is based on a single parameter, the formation probability q, which represents the probability with which incoming larvae form a new nodule. This parameter describes parasite behaviour which cannot easily be recognized in available data without modelling. The estimate for the average formation probability of muq = 0.39 suggests an attraction of the invading infective larvae to already existing nodules or resident worms with probability 0.61. No significant difference in muq was found between the forest and savanna parasite strains. The model can be used inversely to estimate the worm burden of persons from palpation data. The observed variance in the number of nodules per person requires the assumption of a variance-increasing mechanism which was implemented by heterogeneity within the host population (extended model with 2 parameters). Possible reasons for this heterogeneity are presented and its implications concerning the reproductive biology of the parasite are discussed.

Animals↗

Reduced prevalence of onchocerciasis in Uganda following either deforestation or vector control with DDT.

To determine the prevalence of onchocerciasis in western Uganda following deforestation and vector control, three foci were re-examined 20 years after previous surveys. In the Ruteete focus Simulium neavei had apparently disappeared and the prevalence of onchocerciasis declined in adults from about 70% in 1971 to a standardised prevalence of 12% in 1992. An increase of population density together with extended deforestation was assumed as cause of this strong reduction. In Bugoye, a S. damnosum s.l. focus, the standardised prevalence of microfilaria carriers declined from 62% in 1972 to 4.7% in 1992. Entomological data indicated the absence of man biting blackflies in the nineties. It can be suggested that the vector control using DDT performed during the seventies had lead to a change of the species composition from anthropophilic to non-anthropophilic S. damnosum s.l. In the focus Kicheche environmental changes were insignificant, deforestation was not progressive and S. neavei was abundant. Here the standardised prevalence of microfilaria carriers was still high (61%).

Adolescent↗

Identification of Onchocerca volvulus collagen as an antigen mainly recognized by antibodies in chronic hyper-reactive onchodermatitis (sowda).

An Onchocerca volvulus expression library was differentially screened to identify a molecular marker distinguishing sowda (lichenified onchodermatitis) from other onchocerciasis forms. One clone, PG3, was recognized by pooled sera from patients with sowda, but not by pooled sera from patients with generalized onchocerciasis; it was not recognized by sera from patients with lymphatic filariasis or other helminth infections. The DNA of PG3 hybridized strongly with O. volvulus Eco RI-digested DNA, but not with DNA from Brugia spp., Trichinella spp., and humans. A weak reaction was observed with DNA from O. gibsoni and Acanthocheilonema viteae. The PG3 DNA sequence showed a high homology with both human and nematode collagens. Confirmation of the collagen-like nature of the sowda-specific PG3 product was obtained by amino terminal sequencing of the PG3 expression product, as well as by demonstrating its susceptibility to collagenase digestion. The characteristic recognition of the O. volvulus collagen specified by clone PG3 was confirmed by measuring antibody levels to the expressed product in individual sowda and generalized onchocerciasis sera, respectively. Identification of a nematode collagen antigen mainly recognized in sowda patients raises the possibility that this extreme form of dermatitis might arise through cross-reactivity between anti-O. volvulus collagen antibodies and human collagen. However, a relationship between the PG3 recognition by antibodies and the sowda pathogenesis could not be demonstrated.

Amino Acid Sequence↗

Onchocerciasis and human immunodeficiency virus in western Uganda: prevalences and treatment with ivermectin.

Epidemiologic investigations were made to assess the interaction between onchocerciasis and human immunodeficiency (HIV) type 1 infection and the efficacy of ivermectin treatment. Among 1,910 Onchocerca volvulus carriers in a hyperendemic focus, 73 (3.8%) were concurrently infected with HIV and 20 (7.2%) of 276 persons without microfilariae (mf) were HIV-seropositive. A stratified analysis showed no epidemiologic association between onchocerciasis and HIV infection. Consistently, a microfilaria density of 11.9 mf/mg of skin in HIV-positive subjects and 17.7 mf/mg in HIV-negatives ones was observed. During mass treatment of onchocerciasis with a single dose of 150 micrograms/kg of ivermectin, no difference of the efficacy was detected between persons with or without HIV and side effects in the two groups were similar. Even in HIV-positive persons with a reduced ratio of CD4+:CD8+ cells and reduced numbers of CD4+ cells, a significant reduction of their microfilaria density was observed after treatment with ivermectin. Thus, in HIV-endemic areas, the usual dose of ivermectin can be administered during mass treatment.

Adolescent↗

A preliminary assessment of the feasibility of evaluating promising antifilarials in vitro against adult Onchocerca volvulus.

The suitability of motility indices and tetrazolium-based colorimetric assays for the determination of the viability of adult Onchocerca volvulus after in vitro exposure to potential macrofilaricides has been examined. Experimentation showed that both techniques could be applied to adult O. volvulus, although the variability between individual worms necessitated the use of large experimental groups. The potential of using cut anterior tips of female O. volvulus for screening was also investigated. These were shown to give reasonably consistent motility indices, and drug effects were discernible even after 72 h in vitro culture. Application of these viability criteria to studies on the short-term in vitro survival of intact male and female O. volvulus incubated in Eagles MEM plus serum, under 5% CO2 in air, showed this medium to be suboptimal with a greater than 50% loss of worm viability within 144 h of nodulectomy. Males isolated by the collagenase technique were shown to be significantly less viable than dissected males, by both motility indices and tetrazolium reduction. The results highlight the need to use either dissected males, or in the case of females, the need to minimize exposure to collagenase solution. A possible mechanism for selecting a more uniformly viable female worm population is discussed. Examination of the in vitro effects of CGP 20376 using these viability criteria/assay systems showed some delayed suppression of worm motility, but after 120 h in vitro CGP 20376 was not macrofilaricidal against male or female O. volvulus. Male worms were also implanted subcutaneously into gerbils.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Unique recognition of a low molecular weight Onchocerca volvulus antigen by IgG3 antibodies in chronic hyper-reactive oncho-dermatitis (Sowda).

Individual human Ig class responses to Onchocerca volvulus antigens have been evaluated by Western blotting using sera from cases of generalized onchocerciasis and chronic hyper-reactive onchocerciasis (Sowda). in all cases except IgG3 the patterns of recognition by human antibody classes were similar in Sowda and generalized onchocerciasis. Weak or undetectable responses were seen with IgG1, IgG2 and IgM. The total profiles of antigens recognized by the other Ig classes were different, although in some cases certain bands were commonly identified. The result with IgG3, however, was striking. Here, two major antigens (9 kD and 72kD) were recognized by IgG3 antibodies in Sowda sera but not generalized onchocerciasis sera. Furthermore, these two antigens were not recognised by any other Ig class, either in generalized or Sowda onchocerciasis, nor were they detected by antibodies of any class present in a collection of sera representative of other nematode infections. This difference in the IgG3 response was so pronounced that Sowda sera could be distinguished from generalized onchocerciasis sera by an IgG3-specific ELISA assay with a PBS parasite extract as the antigen. Thus, a correlation has been established between one particular clinical condition of onchocerciasis (Sowda) and a serological response, defined in terms of both the parasite antigens and an immunoglobulin class restricted antibody response.

Animals↗

Immunopathologic aspects in human onchocercal lymphadenitis.

Lymph nodes (LN) from 50 patients with generalized onchocerciasis with or without diethylcarbamazine treatment and LN of patients with untreated localized onchocerciasis were studied. Light and electron microscopic examinations and immunostaining (PAP) were performed. In both forms of the disease the majority of microfilariae were degenerated and surrounded either by eosinophils or macrophages. In addition increased number of mast cells and plasma cells was observed. A direct contact between eosinophils and microfilariae, degranulation of eosinophils and free eosinophil granules in the electron dense material around the degenerating microfilariae were registered. The majority of plasma cells produced IgE or IgG. A positive staining for IgE was also present on the surface of mast cells. An extensive hyperplasia of the follicles was a characteristic feature in localized as well as treated generalized onchocerciasis. After anti-IgE staining a heavy intercellular deposition suggesting trapping of immune complexes by dendritic reticular cells developed in the light parts of the germinal centres. Not seldom, IgE producing blast cells were found in the follicles.

Diethylcarbamazine↗

Parasitological studies on "Onchocerca volvulus" eight years after interruption of the transmission in Upper Volta.

The macrofilaria population was analysed in a hyperendemic focus in western Upper Volta to determine the effect of eight years of Simulium control on the adult Onchocerca volvulus. During the first months of 1983 in three neighbouring villages 629 out of 786 inhabitants were examined for onchocerciasis and from 76 patients as far as possible all onchocercomata were extirpated. The macrofilariae were isolated from the nodules after collagenase digestion and examined microscopically. There were no major differences between men and women or different age groups. The average worm burden was 9.8 live macrofilariae per patient. All worms were several years old but developing sperms were found in 94% of the male and embryos in 55% of the female filariae. 36% of all worms were dead and 23% were calcified. Compared with the findings in a Liberian focus with continuous transmission it is concluded that the interruption of the transmission has lead to a reduced worm burden of entirely old worms but that a few more years of control will be needed until the production of microfitariae will end.

Adolescent↗