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PubMed1997

Characterization of human immune responses to the cytosolic superoxide dismutase and glutathione S-transferase from Onchocerca volvulus.

In onchocerciasis patients and in O. volvulus-exposed individuals without signs of onchocericiasis, T- and B-cell responses to two recombinantly expressed O. volvulus enzymes were analysed and compared to responses to total protein extract of adult parasites. The cytosolic enzymes Cu/Zn superoxide dismutase 1 (OvSOD1) and glutathione S-transferase 2 (OvGST2) represent 2 detoxifying molecules which may play an important role in parasite defense against host-induced oxidative stress. The T-cell response to the two recombinant proteins was analysed by investigating the cytokine responses of peripheral blood mononuclear cells. Induction of IL-5 at the mRNA level and IL-5 and IL-10 at the protein level was demonstrated in patients with the generalized form of onchocerciasis and endemic normals without clinical manifestations. IFN-gamma was not found to be induced by either antigen. This pattern of lymphokine expression is indicative of a Th2-type response. Compared to patients with the generalized form, a higher level of cytokine induction was observed in the group of endemic normals. Low but significant IgG levels were observed against OvSOD1 in patients with onchocerciasis; higher antibody levels were found against OvGST2 in patients and endemic normals. The highest IgG levels were detected against the crude O. volvulus extract. These results indicate that the two recombinant O. volvulus proteins induce moderate T and B cell responses.

Adolescent↗
PubMed1993

Antibody responses to Onchocerca volvulus in Ecuadorian Indians and blacks.

In Ecuador, previous epidemiological studies of onchocerciasis affecting a population consisting of Blacks of African origin and Amerindians of the Chachi tribe, have demonstrated different frequencies of clinical disease manifestations in each racial group. To explore the possibility of differential antibody responses to O. volvulus antigens in this population, a subset of sera from these two groups of Ecuadorians with onchocerciasis was analyzed for antibody to O. volvulus antigens using ELISA and Western blot techniques. Significantly higher levels of immunoglobulin against O. volvulus were demonstrated in Chachi Indians compared to native Blacks of African origin: total Ig (p = 0.049), IgG (P = 0.002) IgG4 (p = 0.019) and IgA (p = 0.035). Western blot analysis of sera from 41 persons demonstrated more intense and more frequent recognition of low molecular weight parasite antigens in the Chachi compared to a similar group of male and female Ecuadorian Blacks. These data suggest that the intensity of antibody responses to O. volvulus antigens may reflect the influence of racial factors in the pathogenesis of onchocerciasis in Ecuador.

Adult↗
PubMed1996

Ivermectin distribution in the plasma and tissues of patients infected with Onchocerca volvulus.

OBJECTIVE: To determine the distribution of ivermectin in plasma and tissues of onchocerciasis patients following a single oral dose of 150 micrograms kg-1. SETTING: Medical Department at Soba University Hospital, Khartoum. PATIENTS: Twenty five patients and fourteen healthy volunteers. METHODS: Serial blood samples were obtained from both groups. Tissue samples were removed from various patients as full thickness skin punch biopsies or during nodulectomy. Ivermectin concentration was determined by radioimmunoassay. RESULTS: The plasma pharmacokinetic variables for patients were; maximum plasma concentration 52.0 ng ml-1; time to achieve maximum concentration, 5.2 h.; elimination half life, 35.0 h; and the area under the plasma concentration curve versus time, 2852 ng.h.ml-1. In healthy volunteers, the plasma ivermectin distribution was similar to that in patients, and both groups showed a tendency for a second rise in plasma concentration of the drug suggestive of enterohepatic recirculation. Ivermectin was detected in tissues obtained from patients. Fat showed the highest and most persistent levels, whilst values for skin, nodular tissues, and worms were comparable. Subcutaneous fascia contained the lowest concentrations. CONCLUSIONS: Infection with O. volvulus does not affect the pharmacokinetics of ivermectin, and filarial infected tissues and parasites themselves do take up the drug. There may be prolonged retention of ivermectin because of depot formation in fat tissue.

Adipose Tissue↗
PubMed1994

Heterogeneity of IgG antibody responses to cloned Onchocerca volvulus antigens in microfiladermia positive individuals from Esmeraldas Province, Ecuador.

The prevalence of IgG antibodies to three recombinant O. volvulus antigens, OvMBP/10, OvMBP/11 and OvMBP/29 was determined in a group of 94 microfilaria positive (mf+) individuals resident in the hyperendemic onchocercal area of Esmeraldas Province, Ecuador. Clone OvMBP/11 was the antigen most frequently recognized by patients sera followed by OvMBP/10 and OvMBP/29. When a cocktail of the three recombinant antigens was used the proportion of positive sera increased to 100%. Antibody responses to the fusion partner maltose binding protein (MBP) were low in comparison with those to the cloned antigens and no correlation of responses between individual antigens was observed. The relative level of antibody response to each of the clones in the cocktail varied between individuals. The distribution of IgG responses to OvMBP/11 was bimodal and those to OvMBP/29 and OvMBP/10 were positively and negatively skewed, respectively. When the three recombinant antigens were used in combination this variation was minimized and the pattern of responses showed a normal distribution as was also seen to crude O. volvulus antigen. The cocktail of recombinants thus offers excellent diagnostic sensitivity in combination with the parasite specificity demonstrated previously.

Adolescent↗
PubMed1988

Proposed form to evaluate some histological aspects of macrofilarial morphology, its age dependent alterations and drug related changes in nodules of Onchocerca volvulus and O. gibsoni.

Histological assessment of drug-related pathomorphological changes in macrofilariae of the two nodule forming species Onchocerca gibsoni and O. volvulus is hampered by the variability of age-dependent signs of natural degeneration and the virtual inexistence of clinically established reference medicaments. A specific form was designed to record systematically all characteristics observed in the various organs, tissues, cell types and developmental stages inside normal and drug-affected macrofilariae. Its tabular format permits the synoptic presentation of the findings in all female and male macrofilariae from a particular treated or untreated individual. The proposed form enumerates thirty eight morphological characteristics subdivided into the six subunits cuticle, hypodermis, longitudinal muscle, genital tract, pseudocoelomic cavity and intestinal tract (gut). The normal morphology of sexually mature and productive male and female O. volvulus is described and illustrated by photomicrographs. The cuticle of the male is wrinkled and forms regular striations strictly transverse to the body's longitudinal axis. The longitudinal muscles are well developed and cover almost 100% of the circumference at the anterior and posterior end. Towards the mid-body region the muscular portion diminishes to 50-60% and is replaced there by the very voluminous lateral hypodermic chords. The male genital tract originates with its distal end of the testis close to the anterior end and runs through almost the entire body very close to the posterior end. Spermatogenesis is clearly synchronized and the various development stages are arranged in strict sequential order inside the genital tract. Each type of gonosomal cell may thus serve as a marker of the respective region of the body. The same applies for females where the paired genital tubes run through almost the entire length of the body until the two uteri unite to form a short unpaired vagina. Each of the two reproductive tracts originates at different levels in the posterior part of the female. Because of this, two distinct stages of the sexual products are normally present in sections of the two uteri in the various parts of the female macrofilariae. Towards the anterior end identical stages of embryos may be found. The wide uteri narrow shortly before the vaginal junction to less than 40 microns in the very anterior part of the body. This part is characterized by the voluminous lateral chords of hypodermis and the well developed longitudinal muscles covering greater than 50% of the circumference. Drug-related changes come to light first in this part of the female's body.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗
PubMed2002

Towards a recombinant antigen vaccine against Onchocerca volvulus.

Various approaches to identify potential vaccine candidates against onchocerciasis resulted in the cloning of recombinant proteins, which confer protection in vaccinated mice. The development of an effective vaccine against onchocerciasis has been the focus of a research program supported by the Edna McConnell Clark Foundation from 1985 to 1999. The approaches used to clone potential protective antigens and the successful vaccination of animals with some of the antigens are summarized here.

Animals↗
PubMed2005

Short report: impact of ivermectin community-level treatments on elimination of adult Onchocerca volvulus when individuals receive multiple treatments per year.

A reanalysis of several published reports indicates that when community-wide biannual treatment disrupts transmission of new infection, a profound macrofilaricidal effect of ivermectin (Mectizan) occurs that is accelerated for individuals treated 4 times a year (4x/yr). The effect is particularly obvious on adult male worms and suggests that this gender is susceptible to repetitive treatment after transmission has been blocked or greatly reduced as a result of community treatment.

Animals↗
PubMed2003

Immunopathogenesis of Onchocerca volvulus keratitis (river blindness): a novel role for endosymbiotic Wolbachia bacteria.

River blindness is thought to occur as a result of the host response to degenerating microfilariae in the eye. Utilizing a murine model of corneal inflammation (keratitis) to investigate the immune and inflammatory responses associated with river blindness, we recently demonstrated an important role for endotoxin-like products from endosymbiotic bacteria and for activation of Toll-like receptor 4 (TLR4). These observations have led to a new understanding of the pathogenesis of this disease

Animals↗
PubMed1997

Characterization of a recombinant Onchocerca volvulus antigen (Ov33) produced in yeast.

A yeast (Saccharomyces cerevisiae) expression system has been adapted to produce reagent quantities of a major Onchocerca antigen, Ov33. Using a pool of monoclonal antibodies produced against third-stage larvae, a cDNA library constructed from adult O. volvulus worms was screened. Twenty-seven cDNAs were isolated, two of which had sequence homology to Ov33, a putative aspartyl protease inhibitor, which is the immunodominant antigen of O. volvulus. These cDNAs were expressed at high levels intracellularly or through the secretory pathway of S. cerevisiae. Localization studies using antisera produced against purified recombinant protein demonstrated that Ov33 is a very abundant parasite protein present in the hypodermis, muscle, and uterus of female worms, as well as in embryonic microfilariae. The soluble recombinant protein secreted by yeast (C71) demonstrated inhibitory activity against the aspartyl protease pepsin. Antibodies to the recombinant protein-mediated leukocyte adherence to and killing of skin microfilariae. The sensitivity of a diagnostic test using recombinant Ov33 was evaluated using sera from 441 patients. The mean sensitivities for the two recombinant constructs, C27 and C71, were 82.2% and 85.4%, respectively. The combined sensitivity using both recombinant proteins was 94%.

Animals↗
PubMed2000

Phosphoglucomutase and trehalase isoenzymes of Venezuelan simulium vectors of Onchocerca volvulus.

Phosphoglucomutase (PGM) and trehalase (Tre) isoenzymes of five species of Simulium blackflies (Diptera: Simuliidae), vectors of onchocerciasis in Venezuela, were investigated by means of a portable electrophoresis field kit. Tre differed between S. incrustatum and S. oyapockense s.l. Electrophoretic variation of Tre in other members of the S. amazonicum and S. incrustatum groups merit further investigation. PGM appears to be more useful for separating populations within species complexes. Multiple populations and/or seasonal changes in population structure of S. guianense s.l., S. exiguum s.l. and S. metallicum s.l. were inferred from elecrophoretic variation of PGM.

Animals↗
PubMed2003

Human infection with Onchocerca volvulus in Asir District (Saudi Arabia).

During one academic year, three patients were referred to Parasitology Laboratory from Dermatology Outpatients Clinics in King Abdulaziz University Hospitals. They were diagnosed as Sowda (chronic hyperactive form of onchocerciasis volvulus). The patients came from Asir Region in the Southern of the Kingdom. The lesion was characterized by a sever papule dermatitis localized to the lower limbs, with marked skin darkening. There was extensive follicular hyperplasia of the regional lymph nodes in two cases only. The skin snips taken from the three patients were positive microfilariae. On the other hand, the urine sample of one patient was positive. Six months after the onset of treatment by the clinicians in the Specialized Hospital, skin snips and urine samples were negative.

Adult↗
PubMed2001

Depletion of wolbachia endobacteria in Onchocerca volvulus by doxycycline and microfilaridermia after ivermectin treatment.

Ivermectin is the drug used for mass chemotherapy of onchocerciasis within the WHO African Programme for Onchocerciasis Control. This approach aims to eliminate the disease as a public health problem but using one dose per year may not completely interrupt transmission since it does not suppress microfilaridermia thoroughly enough. Here we show that additional treatment with doxycycline, previously shown to sterilise adult female worms for a few months by depletion of symbiotic wolbachia endobacteria, significantly enhances ivermectin-induced suppression of microfilaridermia, rendering anti-wolbachia treatment a promising basis for blocking transmission by a drug-based approach.

Animals↗
PubMedDate not supplied

Antibody detection tests for Onchocerca volvulus: comparison of the sensitivity of a cocktail of recombinant antigens used in the indirect enzyme-linked immunosorbent assay with a rapid-format antibody card test.

There is a need for a specific, sensitive, and practical diagnostic test to monitor onchocerciasis elimination campaigns. In April 2001, an enzyme-linked immunosorbent assay (ELISA) using 3 recombinant antigens and a rapid-format antibody card test (immunochromatographic test; ICT) using an individual antigen were compared in a Mexican population with onchocerciasis. The sensitivity of the ELISA and ICT was 97% and 86%, respectively.

Adolescent↗
PubMedDate not supplied

Onchocerciasis in Ecuador: changes in prevalence of ocular lesions in Onchocerca volvulus infected individuals over the period 1980-1990.

Trends in prevalence rates of onchocercal ocular lesions were examined over the period 1980 to 1990 using data from two cross-sectional surveys. There was evidence for increasing prevalence of anterior chamber microfilariae, iridocyclitis, optic atrophy, and chorioretinopathy. Large increases in prevalence, in particular, were seen for posterior segment lesions: optic atrophy increased from 2.7% to 6.4% and chorioretinopathy from 8.8% to 35.6%. Greatest increases in these lesions were seen in the Chachi which was attributed to the large increases in prevalence of microfilariae in the anterior chamber particularly in those aged 30 years or greater. The study findings suggest that ocular onchocerciasis is evolving in parallel with the well documented parasitological changes.

Adolescent↗
PubMed1998

The burden of Onchocerca volvulus in Sudan.

Onchocerciasis has been reported in Sudan since 1908 and now prevails in three endemic regions known as the southern, northern and eastern foci. The southern focus is the largest, with nodule and blindness rates exceeding 80% and 12%, respectively, in certain villages. Onchocercal infection in this region causes only a mild skin reaction although microfilarial loads in the skin are high. In contrast, those with onchocerciasis in the northern focus, located between the fourth and fifth Nile cataracts, present with limited but severe skin reactions, low nodule rates (16%), low microfilarial loads in the skin and no ocular involvement. The characteristics of patients from the eastern focus, close to the border with Ethiopian border are similar to those in the north, although most onchocercal skin disease in this area comprises the severe localized pruritus known as sowda.

Animals↗
PubMed1995

Vector competence of Simulium exiguum for Onchocerca volvulus: implications for the epidemiology of onchocerciasis.

In the transmission of human onchocerciasis, competence of the black fly vector influences intensity of transmission by regulating how many infective-stage larvae are produced. The disease is intensifying in Ecuador where Simulium exiguum is a highly efficient limitation-type vector comparable with African forest species in terms of the percentage of flies developing infective-stage larvae and the numbers of larvae per infected fly. In contrast, the endemic foci in Guatemala and southern Mexico have remained stable and closely circumscribed around larval development sites for S. ochraceum, a vector that exhibits a facilitation type of competence and must feed on people with comparatively high microfiladeremia to develop significant numbers of infective-stage larvae. This comparison indicates that assessments of vector competence should be included when planning regional control programs for onchocerciasis.

Adult↗
PubMed1995

Impact of combined large-scale ivermectin distribution and vector control on transmission of Onchocerca volvulus in the Niger basin, Guinea.

As part of the WHO Onchocerciasis Control Programme in West Africa (OCP), the attack phase of operations in the Niger basin in Guinea began in 1989 with the simultaneous use of ivermectin and vector control. Larvicide applications coupled with annual large-scale ivermectin distribution have greatly reduced blackfly infectivity (by 78.8% for the number of infective larvae per 1000 parous flies). The combination of vector control and ivermectin has permitted excellent control of transmission. In the original OCP area, it took 6-8 years of vector control alone to obtain an equivalent decrease in blackfly infectivity. For the same number of flies caught, transmission was much higher in areas where ivermectin had not been distributed. The combined use of ivermectin and vector control has opened up new prospects for carrying out OCP operations with, notably, the possibility of reducing larviciding operations.

Animals↗