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A human case of zoonotic onchocerciasis in Japan.

A 2-year-old girl living in southwestern Japan had a nodule of 2 months' duration on the left foot. A biopsy from the lesion showed transverse sections of a worm surrounded by granulomatous tissue. The worm was identified as an Onchocerca sp. from the morphological characteristics such as relatively thick cuticles, annular ridges on the cortical layer, and high somatic muscles. Positive serological tests using ELISA for Onchocerca gutturosa and Onchocerca volvulus supported the diagnosis. This was the first case of zoonotic Onchocerca infection detected in Japan. The clinicopathological aspects of zoonotic onchocerciasis of this case were discussed.

Child, Preschool↗

The chromosomes of the Filariae.

An understanding of the nature of the chromosomes of the filariae is expected to greatly assist the future interpretation of genome data. Filarial development is not eutelic, and there does not seem to be a fixed number of cell divisions in the way that there is in Caenorhabditis. It is not clear whether the chromosomes of the filariae have localized centromeres or whether they are holocentric. Sex determination is by a chromosomal "balance" X0 system in most filariae, but in some Onchocercidae there has been a chromosomal fusion to create a neo-XY system. It is presumed that the molecular basis of sex determination in filariae is similar to Caenorhabditis. The ancestral karyotype of the filariae is probably 5A+X0, but in some Onchocercidae this has been reduced to 4A+XY, and in O. volvulus and O. gibsoni it has been further reduced to 3A+XY. Onchocerca volvulus and O. gibsoni both have supernumary (B-) chromosomes and in O. volvulus there is a single active nucleolus organising region near the middle of the long autosome.

Journal Article↗

[Immunoenzymatic evaluation of serum IgE in onchocerciasis in Chiapas, Mexico].

Concentrations of total serum IgE were measured by an immunoenzymatic assay (Phadezym-PRIST) in 60 mexican onchocerciasis patients. In order to detect IgE antibodies against adult Onchocerca volvulus antigens, separately six onchocerciasis sera were depleted of IgE antibodies by using a mixture of Onchocerca gutturosa, Ascaris suum and Fasciola hepatica antigenic extracts coupled with sepharose 4B. Additionally, the sera were incubated with an adult O. volvulus antigenic extract coupled with sepharose 4B. The differences found between the IgE levels before and after incubation with heterologous antigens show that the median IgE value against O. volvulus adults antigens varies between 20 and 65 percent of the total serum IgE.

Adolescent↗

Mepacrine--ineffective in onchocerciasis.

Mepacrine in doses of 200 mg b.d. for 5-7 days given to six patients from the rain-forest zone of Nigeria showed neither micro- nor macrofilaricidal activity against Onchocerca volvulus.

Adult↗

The Beffa form of Simulium soubrense of the S. damnosum complex in Togo and Benin.

The Beffa form of Simulium soubrense Vajime & Dunbar, a member of the S. sanctipauli sub-complex of the S. damnosum complex, was found breeding throughout rivers in the Togo-Benin Gap, as far north as 9 degrees 30'N. Its distribution changed with the season. In southern Togo there were seasonal fluctuations in the relative abundancies of the Beffa form and of S. damnosum/S.sirbanum. There was considerable temporal and regional variation in the frequencies of different colour morphs of adult flies. The flies in Benin tended to be darker. Infections with Onchocerca volvulus (Leuckart) appeared to be independent of the host's colour morph category. Larger flies harboured significantly more first stage Onchocerca larvae but no significant relations with fly size were found for second and third stage larvae.

Animals↗

The major radioiodinated cuticular antigens of Onchocerca gibsoni microfilariae are neither species nor onchocerca specific.

The possible role of microfilarial surface (cuticular) antigens in immuno-diagnosis of human filarial infections has been assessed using microfilariae (mf) of the cattle parasite Onchocerca gibsoni. A Triton X-100 extract of 125I-labeled O. gibsoni mf was reacted with a panel of sera from humans infected with Onchocerca volvulus, Wuchereria bancrofti and Schistosoma japonicum as well as sera from uninfected controls. Results of these immunoprecipitations indicated that sera from humans infected with O. volvulus or W bancrofti contain antibody specificities recognising certain of the radioiodinated cuticular proteins of O. gibsoni mf. Two-dimensional gel analysis and subsequent autoradiography of these immunoprecipitates showed that 8 radioiodinated proteins recognised by sera from calves injected with O. gibsoni mf were also immunoprecipitated by sera from humans infected with either O. volvulus or W. bancrofti. Thus there appear to be no major radioiodinated cuticular antigens of O. gibsoni mf which are species or onchocerca specific.

Animals↗

Failure of furazolidone in the treatment of onchocerciasis.

12 adult onchocerciasis patients from the rain forest zone of Nigeria were treated with furazolidone in divided daily doses ranging from 5--15 mg per kg body weight for 7--21 days to a maximum total dose of 6.3 g. The drug showed neither micro- nor macrofilaricidal activity against Onchocerca volvulus.

Adolescent↗

Entomologic considerations in the study of onchocerciasis transmission.

The entomological resources utilized for a better understanding of Onchocerca volvulus transmission are discussed in this paper. Vector density, anthropohilia, gonotrophic cycyle, parous condition longevity and probability of survival in days after the infectious meal are assessed here in order to integrate an overall picture. The concept of vectorial capacity is developed stressing the quantitative aspects. Parasitism of the black-flies by filariae that are doubtfully identified as O. volvulus is also mentioned here.

Animals↗

A case of idiopathic scrotal gangrene (Fournier) with perineal extension.

A case of idiopathic or Fournier's gangrene of the scrotum is described with unusual extension to the perineum. The clinical features of this disease are summarized. The literature is reviewed for extra genital extension of this gangrene of unknown aetiology. Coincidental association between infections with Onchocerca volvulus and scrotal gangrene was observed.

Adult↗

Biochemical and immunochemical characterisation of a 20-kilodalton complex of surface-associated antigens from adult Onchocerca gutturosa filarial nematodes.

Surface radioiodination of adult Onchocerca parasites reveals a restricted range of proteins associated with the cuticle. We present data to show that prominent among these is a complex of low-molecular-weight proteins which can be released in soluble form by homogenisation of surface-labelled Onchocerca gutturosa in phosphate-buffered saline (PBS). One of this groups of proteins, designated gp20, has a molecular mass of 20,000, is glycosylated with two N-linked carbohydrate side chains, and has a basic pI. Other PBS-soluble, 125I-labelled proteins of similar size appear not to be glycosylated. A distinct group of molecules are released only in the presence of reducing agents, and are likely to be cuticular collagens. The low-molecular-weight components are antigenic and cross-reactive with Onchocerca volvulus infection sera. Cross-reactions are also observed in immunoprecipitation experiments using sera from Brugia-immunised animals and infected humans. Comparative two-dimensional analyses of these immunoprecipitates reveal at least two Onchocerca specific components. As an alternative to radiolabelling and PBS homogenisation, incubation of worms in medium containing the reducing agent 2-mercaptoethanol resulted in a similar set of molecules being released into the medium. Since surface antigens of O. gutturosa from bovines and O. volvulus from humans appear similar in size and are antigenically cross-reactive, the more readily available parasite is being used to study further the properties of these molecules and to provide reagents for raising antisera reactive to the equivalent O. volvulus antigens.

Animals↗

Onchocerca antigens in protection, diagnosis and pathology.

Characterization of the immune response to Onchocerca volvulus is important for the diagnosis, control and understanding of the disease it causes. The antibody response to surface, secreted and somatic antigens of the worm has therefore been examined at an individual immunoglobulin (Ig) class level, by using a panel of different human sera. Onchocerca-specific antigens tend to be of low molecular mass and preferentially recognized by IgG4 and IgE. There is considerable cross-reaction between O. volvulus and O. gibsoni, so that the latter may be an alternative source of material for use in diagnosis. A surface-enriched fraction of low molecular mass appears to be a most promising diagnostic tool. Amongst somatic antigens, two were uniquely recognized by IgG3 antibodies in sera from sowda patients, thereby providing a molecular correlate for a recognized pathological condition. Improved diagnosis is needed for detecting infection in both humans and the vector. Our target for detection in humans is a continuously released, nonimmunogenic product, which is ideally stage and parasite specific. The excretions of adult worms do contain components not recognized by antibodies in infected serum, but we cannot rule out that these are of host, rather than parasite origin. Excretions of Litomosoides carinii contain both host and parasite molecules and, in addition, stage-specific and sex-specific components. Unfortunately, however, the rate of production of excretions varies during the life of L. carinii. This finding may be relevant to the detection of Onchocerca excretions if they are produced at a similarly uneven rate. Finally, for detecting infective larvae in the vectors, we are currently screening a genomic library of O. volvulus for an appropriate probe. To date, one DNA sequence has been cloned that shows promising specificity.

Animals↗

Surface antigens of male worms and microfilariae of Onchocerca gibsoni.

Living adult males and microfilariae of the cattle filarial parasite Onchocerca gibsoni were externally labelled with radioactive iodine using the iodogen and Bolton-Hunter procedures. Characterization of labelled surface proteins by sodium dodecyl sulphate (SDS)-polyacrylamide gel electrophoresis revealed clear cut differences in the two life cycle stages. In addition, the two radiolabelling procedures yielded some differences in the profiles of radiolabelled surface proteins for both adults and microfilariae. Immunoprecipitation analysis revealed a number of labelled antigens recognized by antibodies in human onchocerciasis serum pools, thereby demonstrating the usefulness of O. gibsoni as a model in Onchocerca volvulus vaccine studies. The reactivity of microfilarial antigens extended to antibodies from other human nematode infections, whereas male surface antigens, particularly those of low molecular weight, were Onchocerca specific. This indicates that O. gibsoni can provide a convenient source of specific diagnostic antigen.

Animals↗

Analysis of ecdysteroids in Onchocerca gibsoni, O. volvulus and nodule tissues.

Free ecdysteroids were detected in Onchocerca gibsoni, in tissues constituting O. volvulus and O. gibsoni nodules and in unrelated bovine tissues. Ecdysone and 20-hydroxyecdysone were identified by HPLC-RIA and GC/MS(SIM). The concentration of free ecdysteroids in the nodule tissue immediately surrounding the parasites was at least an order of magnitude higher than that detected in the worms themselves, or in adjacent nodular tissues or other bovine tissues.

Abattoirs↗

Intradermal reactivity of excretory and secretory products of onchocercal microfilariae.

The intradermal reactivity of excretory and secretory (ES) products derived from the in vitro cultivation of onchocercal microfilariae was evaluated. The ES products from Onchocerca volvulus were highly sensitive in the detection of active onchocerciasis in both Liberian and Guatemalan subjects. A low level of cross-reactivity occurred in patients with loaisis and in dogs with Dipetalonema reconditum, but not in dogs with Dirofilaria immitis. ES products from O. gutturosa evoked reactions in Guatemalan subjects, but were not as sensitive as those from O. volvulus.

Antigens↗

Pathogenesis of onchocercal keratitis (River blindness).

Onchocerciasis is a major cause of blindness. Although the World Health Organization has been successful in reducing onchocerciasis as a public health problem in parts of West Africa, there remain an estimated 17 million people infected with Onchocerca volvulus, the parasite that causes this disease. Ocular pathology can be manifested in any part of the eye, although disease manifestations are frequently characterized as either posterior or anterior eye disease. This review focuses on onchocerca-mediated keratitis that results from an inflammatory response in the anterior portion of the eye and summarizes what is currently known about human disease. This review also describes studies with experimental models that have been established to determine the immunological mechanisms underlying interstitial keratitis. The pathogenesis of keratitis is thought to be due to the host inflammatory response to degenerating parasites in the eye; therefore, the primary clinical symptoms of onchocercal keratitis (corneal opacification and neovascularization) are induced after injection of soluble O. volvulus antigens into the corneal stroma. Experimental approaches have demonstrated an essential role for sensitized T helper cells and shown that cytokines can regulate the severity of keratitis by controlling recruitment of inflammatory cells into the cornea. Chemokines are also important in inflammatory cell recruitment to the cornea, and their role in onchocerciasis is being examined. Further understanding of the molecular basis of the development of onchocercal keratitis may lead to novel approaches to immunologically based intervention.

Animals↗

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↗

[Attempt to isolate from Ascaris suum an antigenic fraction for use in the immunologic diagnosis of onchocerciasis].

For the purpose of immunological diagnosis of onchocerciasis, the authors attempted to isolate an antigenic fraction from Ascaris suum which would only detect anti-Onchocerca volvulus antibodies. Chromatofocusing was done on a crude antigenic preparation from the ascaris. Immunoelectrophoresis showed that the fraction eluted between pH 5.6 and pH 4.9 contained antigens which reveal anti-Onchocerca antibodies; anti-Loa loa antibodies are revealed by the fraction eluted at pH less than 4. From the fraction which reveal anti-Onchocerca antibodies, affinity chromatography isolated a system in which three components were detected by electrofocusing at a Pi of about pH 5.5. The specificity and sensitivity of this system are being studied.

Animals↗

Resistance to Onchocerca lienalis microfilariae in mice conferred by egg antigens of homologous and heterologous Onchocerca species.

Embryonic stages of various Onchocerca species have been used to stimulate resistance in CBA mice to challenge injections with the microfilariae of Onchocerca lienalis. Comparable levels of resistance to challenge (29-37% reductions) were conferred by living, freeze-killed, or sonicated organisms administered with Freunds' Complete Adjuvant (FCA). Antigens extracted in saline, or with the detergent sodium deoxycholate, were also protective. Adjuvants enhanced the protective effect, particularly FCA (78% reduction), Freunds' Incomplete Adjuvant (74% reduction), aluminum hydroxide (70% reduction) and Bordetella pertussis (70% reduction). Detergent extracts prepared from intact embryos with n-octyl glucoside also stimulated significant levels of protection against microfilarial challenge when given with FCA (37-45% reductions). Levels of resistance induced by immunizations with intact organisms were greatest following subcutaneous (s.c.) injection over the neck or by intramuscular inoculation. Soluble extracts were also particially effective given by s.c. inguinal or intraperitoneal injection. A time-interval of greater than 3 weeks between the completion of immunization and challenge was required for the expression of immunity. Cross-protection against challenge with O. lienalis microfilariae was also afforded to mice by immunization with intact embryos or detergent extracts of Onchocerca gutturosa (45 and 34% reductions), Onchocerca gibsoni (66 and 47% reductions) or Onchocerca volvulus (58 and 41% reductions). It is concluded that the embryonic stages of both human and animal parasites provide a source of cross-protective antigens of value in studies on resistance to Onchocerca microfilariae in experimental hosts.

Animals↗