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PubMed1983

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↗
PubMed1968

The effects of drugs on Onchocerca volvulus. 3. Trials of suramin at different dosages and a comparison of the brands Antrypol, Moranyl and Naganol.

Suramin and Mel W are the only two drugs at present known to be effective against the adult worms of Onchocerca volvulus, but in view of the unpredictable occurrence of fatal arsenical encephalopathy in a small proportion of patients receiving Mel W, suramin remains the preferred macrofilaricide in the treatment of onchocerciasis. It is therefore important to determine the suramin dosage schedules that will produce parasitological cures with minimal concomitant risks of toxic reactions. The criteria by which cures should be judged must also be appreciated.Courses of different duration and employing doses of 1.0 g, 0.5 g and 0.25 g suramin have been investigated for their action on adult worms and microfilariae, for the toxic reactions which they produce on the kidney, and for the level of suramin reached in the serum during treatment. A course of 5 or 6 weekly doses of 1.0 g has been shown to be the optimum for adults.It is sometimes stated without good foundation that different brands of suramin differ in their purity and chemical composition, thus producing inconsistent effects on the parasites and grave risks of toxic manifestations. The three main brands in current use in Africa (Antrypol, Moranyl and Naganol) have therefore been compared in a group of patients, using the same optimum dosage schedule for each preparation and recording the action of the various brands on the parasites, as well as their comparative toxicities and the serum suramin levels achieved. No significant differences between the brands were recorded.

Clinical Trials as Topic↗
PubMed1968

Experiments on the chemoprophylaxis of Onchocerca volvulus infection.

Previous work on monkeys and on human volunteers led to the development of a schedule of diethylcarbamazine dosage suitable for the chemoprophylaxis of loiasis. In several parts of Africa where this chemoprophylaxis is practised against Loa loa, infections with Onchocerca volvulus are also common. Attempts were therefore made to determine whether diethylcarbamazine has any prophylactic action against the latter parasite by making use of chimpanzees exposed to experimental infections, and also by using biopsy techniques to study the fate of infective larvae inoculated into volunteers.Both experimental methods proved more difficult to apply in O. volvulus infections than had been the case with L. loa, but evidence was obtained that diethylcarbamazine is not an effective chemoprophylactic for O. volvulus.Further experiments were then carried out with suramin and with melarsonyl potassium (Mel W). Although both gave some evidence of partial prophylactic activity, their use for this purpose is at present neither practical nor safe.

Animals↗
PubMed2005

A randomized, double-blind, controlled trial of the effects of ivermectin at normal and high doses, given annually or three-monthly, against Onchocerca volvulus: ophthalmological results.

A three-year randomized, controlled, double-blind trial was conducted in Cameroon to determine whether ivermectin, given at three-monthly intervals and/or at high doses (800 microg/kg), had a greater effect on adult Onchocerca volvulus than standard doses (150 microg/kg annually). As several patients complained of transitory subjective visual problems after treatment, some of them being of an unexpected type, we organized two series of detailed ophthalmological examinations to evaluate whether they were associated with ocular lesions. Analysis showed that these complaints were significantly more frequent in the two groups treated with high doses of ivermectin than in the reference group. In the ophthalmological examinations, the only differences recorded between the groups were a lower prevalence and mean number of microfilariae in the anterior chamber in the groups treated three-monthly, and, at the first examination round, a higher prevalence of early lesions of the iris in the group treated at high doses annually. These findings do not allow us to explain the cause of the transitory ocular complaints, nor why they were more frequent in the groups treated at high doses. However, one may conclude that using doses of ivermectin higher than the standard one should be considered with caution.

Adolescent↗
PubMed2002

Bacterial endosymbionts of Onchocerca volvulus in the pathogenesis of posttreatment reactions.

Treatment of onchocerciasis with diethylcarbamazine (DEC) or ivermectin is associated with a posttreatment reaction characterized by fever, tachycardia, hypotension, lymphadenopathy, and pruritus. To investigate the role of the Wolbachia bacterial endosymbiont of Onchocerca volvulus in these reactions, serum samples collected before and after treatment with either anthelmintic were assessed for evidence of Wolbachia DNA. By use of real-time quantitative polymerase chain reaction, Wolbachia DNA was detected in both groups-with significantly higher levels in those who received DEC (P <.0001). In the ivermectin group, there was a significant correlation between levels of bacterial DNA and serum tumor necrosis factor-alpha (P =.013). Peak DNA levels correlated with reaction scores (P =.048). Significant correlations were also seen between Wolbachia DNA and the antibacterial peptides calprotectin (P =.021) and calgranulin B (P <.0001). These findings support a role for Wolbachia products in mediating the inflammatory responses seen following treatment of onchocerciasis and suggest new targets for modulating these reactions.

Adolescent↗
PubMed1976

Antigenic diversity among Onchocerca volvulus in Nigeria, and immunological differences between onchocerciasis in the savanna and forest of Cameroon.

Onchocerciasis is a remarkably chronic infection and, in West Africa, there are distinct clinical and pathological differences between the disease in the savanna and in the forest. Experiments were carried out to see whether antigenic diversity among Ochocerca volvulus worms might contribute to these features. Extracts of adult worms and or microfilariae were analysed by disc electrophoresis on polyacrylamide gels and showed a remarkable diversity of protein patterns but no consistent savanna/forest or Nigeria/Cameroon differences. Indirect haemagglutination using cross-absorbed sera was used to look for antigenic diversity or identity between different O. volvulus worms. Sera of patients were absorbed with antigens extracted from worms taken from those paitents and then titrated against sheep erythrocytes coated with the same antigens. It was shown that an adult Onchocerca volvulus could be either antigenically identical with, or distinct from, another worm taken from the same patient. In one Nigerian village identity was shown in two instances nad diversity in five. Microfilariae lack some antigens possessed by adult worms. This test has shown consistent savanna/forest differences in worm antigen patterns and antibody responses. In order to explain the pattern of these differences it was necessary to postulate that forest patients possessed antibodies to another worm which had antigens in common with savanna Onchocerca. The relevance of these findings to the pathology and prevention of onchocerciasis is discussed.

Antigens↗
PubMed2000

The secretory Onchocerca volvulus protein OvS1/Ov20 exhibits the capacity to compete with serum albumin for the host's long-chain fatty acids.

The mechanism by which filarial parasites derive fatty acids bound to the host's carrier protein is poorly understood. The capacity of a secretory protein of Onchocerca volvulus (OvS1/Ov20) to compete with serum albumin for arachidonic and other fatty acids was investigated in this study. Binding affinities of the two proteins for the long-chain fatty acids were determined using displacement assays. The fluorescent probes used included 11-((5-dimethylaminonaphthalene-1-sulfonyl)amino) undecanoic acid (DAUDA) and cis-parinaric acid. OvS1 protein bound arachidonic acid with an affinity five-fold greater than the affinity exhibited by serum albumin. Oleic acid was bound by the parasite protein with an affinity two-fold greater than the affinity shown by serum albumin. Furthermore, the affinities exhibited by OvS1 protein in binding arachidonic and linoleic acid were about two times higher than the affinity for oleic acid. The results suggest that the OvS1 protein has the capacity to compete with the main host's fatty acid carrier protein for the long-chain fatty acids, in particular arachidonic acid, the precursor for eicosanoids.

Animals↗
PubMed1983

Diagnosis of Onchocerca volvulus infection in Guatemalan children.

Nodule examination, the Mazzotti test (a provocative challenge with diethylcarbamazine), and the enzyme-linked immunosorbent assay (ELISA) were compared for diagnostic efficacy in children who were born in an area endemic for onchocerciasis in Guatemala and were skin-biopsy negative for microfilaria of Onchocerca volvulus. Four groups of children under 16 years of age were formed based upon the possible combinations of nodule positivity or negativity and ELISA positivity or negativity. Only those children with a positive (greater than or equal to 1:160) ELISA titer had a positive Mazzotti test (9 of 20 tested), regardless of the presence or absence of nodules. These results suggest that the current ELISA serology is highly sensitive for low density infections, and should be considered in surveys for the incidence of new Onchocerca infections.

Adolescent↗
PubMed1992

Anti-Onchocerca volvulus immunoglobulin subclass response in children from Sierra Leone.

The humoral immune responses of a paediatric population of 224 children, 2-15 years of age, residing in an onchocerciasis endemic area of Sierra Leone, were studied to gain information that may be useful in the serodiagnosis of prepatent and low-level infections with Onchocerca volvulus. The antigen-specific levels of IgG and IgG4 were determined and evaluated in the context of the parasitological status of the child. Over 87% of the microfilaria-negative children had significant levels of antigen-specific antibodies against O. volvulus, suggesting that a large percentage of this paediatric population were harbouring prepatent or low-level infections. Over 60% of the children in the group that had detectable numbers of microfilariae in skin snips had elevated levels of O. volvulus-specific IgG4. In contrast, only 23% of the microfilaria-negative children had detectable IgG4 responses. The results presented here indicate that measures of O. volvulus-specific IgG4 may be a useful indicator of the parasitological status of children during the very early stages of onchocerciasis.

Adolescent↗
PubMed1992

Serological cross-reactivity between a human Ro/SS-A autoantigen (calreticulin) and the lambda Ral-1 antigen of Onchocerca volvulus.

We have cloned and sequenced a 46-kD Ro/SS-A autoantigen gene that is the human homologue of the calcium-binding protein, calreticulin. The sequence of this 46-kD Ro/SS-A protein (calreticulin) has significant homology to lambda Ral-1, a recombinant cDNA clone corresponding to a major antigen of the nematode, Onchocerca volvulus, the infectious agent of onchocerciasis. We therefore sought to determine whether antibodies produced by onchocerciasis patients might crossreact with the human 46-kD Ro/SS-A autoantigen (calreticulin). 20 of 22 sera from Liberian onchocerciasis patients who had no known evidence of autoimmune disease were found to contain antibodies that reacted with the 46-kD Ro/SS-A (calreticulin) by immunoblot analysis. Characteristic of sera reactive with Ro/SS-A antigens, some onchocerciasis sera also immunoprecipitated the Ro/SS-A-associated hY RNAs. In addition, a monoclonal antibody raised against O. volvulus organisms reacted to purified human WiL-2 cell 46 kD Ro/SS-A antigen (calreticulin) by ELISA. These results strongly suggest that onchocerciasis patients produce antibodies that crossreact with the 46-kD human Ro/SS-A autoantigen (calreticulin) and raise the possibility that infectious organisms such as O. volvulus might play a triggering or exacerbating role in the human Ro/SS-A autoimmune response.

Amino Acid Sequence↗
PubMed1987

Infection rates and parasitic loads of Onchocerca volvulus, and other filariae, in Simulium sanctipauli s.l. and S. yahense in a rain-forest area of Liberia.

Simulium sanctipauli s.l. and S. yahense are common and widespread in the rain-forest zone of Liberia, but differ with regard to their biting densities and contribution to the transmission of Onchocerca volvulus. Although, in a study area on the St. Pauli River, S. sanctipauli s.l. (presumably S. soubrense in the sense of Post) was the predominant ma-biting species (74.3% of 30,855 females examined), S. yahense was shown to be the important vector. While 1000 biting females of S. yahense carried 96 3rd stage larvae indistinguishable from O. volvulus, only 14 were found per 1000 females of S. sanctipauli s.l. Of the parous females (3135 S. sanctipauli s.l./1621 S. yahense) 23.8/39.9% harboured 1st and/or 2nd stage filarial larvae and 1.9/9.4% 3rd stage larvae of O. volvulus. Animal filariae of unknown origin, indicative of zoophily, were very common in S. sanctipauli s.l. (13.8%) but practically absent from S. yahense (0.5%). In spite of its poorer vectorial performance S. sanctipauli s.l. cannot be neglected as a vector because it may occur in high biting densities and contribute considerably to the transmission, in particular in the vicinity of the St. Paul River. The interplay of two vector species, which develop in different types of water-courses explains the overall high endemicity of onchocerciasis in the study area.

Animals↗
PubMed1991

Suramin and the time it takes to kill Onchocerca volvulus.

The paper records the numbers of 1-2 mm shotty papules developing in the author's skin after 2-day courses of diethylcarbamazine (DEC) repeated every 16 days before, during and after a 7.1 G suramin course for cutaneous onchocerciasis. Assuming, from biopsy evidence, that each papule represented a dead Onchocerca volvulus microfilaria (mf), the number of mfs reaching the skin every 16 days did not begin to fall until 96 days after the first full dose of suramin; and only reached zero by day 224. The histopathology of nodules excised from Cameroonian patients before, and at intervals of 56-335 days after, the start of a 7.1 G suramin course, revealed changes in the worms that correlated over time with the disappearance of mfs from the skin. Suramin sterilized and killed the male worms between days 77 and 105 and, in the females, it adversely affected the staining and subsequent development of small morulae from about day 56. It was estimated that new embryogenesis ceased about 56-77 days after the first full dose; development of the last viable embryos to mfs was complete by about 136 days; and the last mfs, perhaps having reduced vitality, emerged from the females by 160 days and reached the skin within 16-32 days.

Adult↗
PubMed1973

Daytime variation in the density of Onchocerca volvulus microfilariae in human skin.

One aim of this study was to determine whether a corneal-scleral punch biopsy instrument provides skin specimens of sufficiently uniform size so as to eliminate the need to weigh or measure the specimens in order to provide a reproducible index of the density of Onchocerca volvulus microfilariae in the skin. A second aim was to determine whether the density of microfilariae in the skin varies with the time of day. The reports of others on the latter are contradictory. Duplicate skin specimens were taken from 10 people four times during one day with a corneal-scleral punch biopsy instrument. Each specimen was weighed and measured, and the number of microfilariae were counted. Although the specimens were not of uniform weight or surface area, the number of microfilariae per specimen was as good an index of the density of larvae in the skin as the number of microfilariae per mg, or per mm(2) of skin. This may not be true when other methods of procuring skin specimens are utilized. A universally acceptable standard method is advocated. The density of microfilariae in the skin approximately doubled from morning to midday, and began to decline by early evening.

Adult↗
PubMed1990

Possible transplacental transmission of Onchocerca volvulus.

In a recent epidemiological study on onchocerciasis on the lower Jos Plateau in Nigeria, a 7-month-old baby delivered by a mother suffering from onchocerciasis showed early clinical signs of the disease: pruritus was present all over the body. The infant's skin snip on incubation revealed microfilariae of Onchocerca volvulus. These findings were confirmed 3 months later when the child was re-examined. No onchocercal nodule was found, but pruritus persisted.

Female↗
PubMed1984

Modelling the migration of Onchocerca volvulus in simuliids, using a simple compartmental process.

A simple compartmental process, which is time-homogeneous and has differing transition rates between compartments, is discussed. When such a process is hierarchical, with all individuals released into the first compartment, the resulting distribution of individuals over the various compartments is multinomial. This process is applied to the migration of Onchocerca volvulus in simuliids and appears to represent successfully the early migration from the stomach through the abdomen to the thorax, provided that allowances are made for the engorgement period and the encapsulation of the blood meal by a peritrophic membrane.

Animals↗
PubMed1977

Preliminary studies on the histochemical differentiation of strains of Onchocerca volvulus microfilariae in Togo.

Skin snips were taken from 75 people living in four villages of northern Togo. The 7824 microfilariae that emerged were examined by staining for the presence of acid phosphatase. Four distinct patterns of enzyme staining were observed, and descriptions of the stained microfilariae are given. The study confirms the view that a number of biological strains or variants of Onchocerca volvulus coexist in West Africa, and suggestions are made for further research that could result in the practical application of these observations in onchocerciasis control programmes.

Animals↗