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Hyperreactive onchocerciasis exhibits reduced arachidonate and linoleate levels in serum triglycerides.

The mechanism by which the minority of patients with onchocerciasis exhibiting the hyperreactive (sowda) form of the disease may be able to kill the microfilariae of Onchocerca volvulus is still poorly understood. In this study, the relative amounts of arachidonate and linoleate in serum phospholipids and triglycerides were investigated by gas chromatography both in patients infected with O. volvulus who exhibited either a hyperreactive or a generalized form of onchocerciasis and in persons with no filarial infections. Remarkable differences were observed in the serum triglycerides but not in the phospholipids. In comparison to persons without any filarial infection, significantly lower relative amounts of arachidonate--indicated by elevated triene-tetraene ratios--and of linoleate--indicated by lower diene + tetraene - triene values--were detected in patients with hyperreactive onchocerciasis, and less pronounced differences were found in persons with generalized onchocerciasis. The relationship between reduced amounts of arachidonate and linoleate in serum triglycerides and possible implications on the eicosanoid production in the host-parasite relationship leading to parasite elimination are discussed.

Adolescent↗

Onchodermal skin disease in a hyperendemic onchocerciasis focus in western Uganda.

To assess the degree of skin disease in Simulium neavei s.s.-transmitted onchocerciasis, 72 patients infected with Onchocerca volvulus in the Kabarole district of Uganda were studied. They were clinically and parasitologically evaluated. Onchocercal skin lesions were determined using a modified Murdoch skin assessment, and skin scores were calculated. The chronic skin score (4.0) was associated with age, and the acute skin score (8.5) was significantly higher in males. The burden of onchocercal skin lesions was found to be high in most patients. The number of nodules (median number 1.9) and the microfilarial load (geometric mean of microfilaria 11.5) were not determinants for the burden of onchocercal skin disease in infected individuals. The study concludes that onchodermatitis is a serious medical condition in Kigoyera Parish and needs to be considered in all efforts to control onchocerciasis.

Adolescent↗

A novel cyclophilin from parasitic and free-living nematodes with a unique substrate- and drug-binding domain.

A highly diversified member of the cyclophilin family of peptidyl-prolyl cis-trans isomerases has been isolated from the human parasite Onchocerca volvulus (OvCYP-16). This 25-kDa cyclophilin shares 43-46% similarity to other filarial cyclophilins but does not belong to any of the groups previously defined in invertebrates or vertebrates. A homolog was also isolated from Caenorhabditis elegans (CeCYP-16). Both recombinant O. volvulus and C. elegans cyclophilins were found to possess an enzyme activity with similar substrate preference and insensitivity to cyclosporin A. They represent novel cyclophilins with important differences in the composition of the drug-binding site in particular, namely, a Glu(124) (C. elegans) or Asp(123) (O. volvulus) residue present in a critical position. Site-directed mutagenesis studies and kinetic characterization demonstrated that the single residue dictates the degree of binding to substrate and cyclosporin A. CeCYP-16::GFP-expressing lines were generated with expression in the anterior and posterior distal portions of the intestine, in all larval stages and adults. An exception was found in the dauer stage, where fluorescence was observed in both the cell bodies and processes of the ventral chord motor neurons but was absent from the intestine. These studies highlight the extensive diversification of cyclophilins in an important human parasite and a closely related model organism.

Amino Acid Sequence↗

Temporal recruitment of neutrophils and eosinophils to the skin in a murine model for onchocercal dermatitis.

The parasitic helminth Onchocerca volvulus causes ocular onchocerciasis (river blindness) and onchocercal skin disease. To understand the immunologic basis for early stage skin disease, we developed a model in which C57B1/6 mice were immunized subcutaneously and injected intradermally (in the ear) with soluble O. volvulus antigens (OvAg). We found that ear thickness increased significantly after intradermal injection of OvAg and remained elevated for at least 7 days. Dermatitis was dependent on prior immunization, and was associated with an intense cellular infiltrate in the dermis. Neutrophils were the predominant inflammatory cells in the dermis 12 hr after intradermal injection, with only occasional eosinophils present. Conversely, increased ear thickness at later time points was associated with eosinophils, and neutrophils were only rarely detected. Both cell types were present at intermediate time points. These data indicate that recruitment of neutrophils and eosinophils to the skin is temporally regulated.

Animals↗

Prevalence, geographical distribution and clinical manifestations of onchocerciasis on the Island of Bioko (Equatorial Guinea).

A survey for the prevalence, geographical distribution and clinical manifestations of onchocerciasis was conducted on the Island of Bioko (formerly Fernando Póo), Equatorial Guinea, between 1987-89. The whole population (1799 inhabitants) of thirteen villages distributed around the island was surveyed. Identification data, physical examination and Snellen "E" test for visual acuity were performed. Skin snips were taken from both iliac crests and right scapula and calf. Differential diagnosis between Onchocerca volvulus and Mansonella streptocerca was carried out in both fresh and Giemsa stained preparations. The overall prevalence (+ skin snips) and mean microfilarial density were 75.2% (range 51.9% to 87.1%) and 32.2 mf/snip respectively. Skin snips showed a higher microfilarial density from iliac crests. The following clinical manifestations were found: 560 (31.2%) with nodules; 518 (28.8%) with dermatitis, pigmentation changes and cutaneous atrophy; 753 (41.9%) with lymphoadenopathy and lymphoedema. Blindness due to different causes was registered in 13 cases (0.8%). The results showed that onchocerciasis is hyperendemic and widespread over the island. It is estimated that almost the whole population (62,000) is at risk of infection.

Adolescent↗

Density-dependent processes in the transmission of human onchocerciasis: relationship between the numbers of microfilariae ingested and successful larval development in the simuliid vector.

A previous paper reported that the intake of Onchocerca volvulus microfilariae (mff) by different species of Simulium is essentially proportional to the parasite load in the skin of infected carriers. This paper examines the fate of the ingested mff in susceptible vectors to assess the relationship between parasite intake and infective larval output in blackfly species with and without well-developed cibarial armatures. Analysis is based on data from 3 onchocerciasis endemic areas: Guatemala (S. ochraceum s.l.), West Africa (S. damnosum s.l./S. sirbanum) and the Amazonian focus between South Venezuela and Northern Brazil (S. guianense and S. oyapockense s.l.). The data, which include published and unedited information collected in the field, record experimental studies of parasite uptake by wild flies maintained in captivity until the completion of the extrinsic incubation period. The relationship between L3 output (measured as the mean number of successful larvae/fly or, as the proportion of flies with infective larvae) and average microfilarial intake, was strongly non-linear. This non-linearity was best represented by a sigmoid function in case of armed simuliids (S. ochraceum s.l., S. oyapockense s.l.), or by a hyperbolic expression in that of unarmed flies (S. damnosum s.l., S. guianense). These results are compatible, respectively, with the patterns of 'initial facilitation' and 'limitation' described in culicid vectors of lymphatic filariases. A maximum mean number of 1-3 L3/fly was observed in all 4 vectors. It is concluded that O. volvulus larval development to the infective stage is regulated by density-dependent mechanisms acting at the early phase of microfilarial migration out of the blackfly's bloodmeal. Damage by the bucco-pharyngeal armature may also be density dependent. A hypothesis, based on this density dependence is forwarded to explain initial facilitation, so far only recorded in vectors with well-developed cibarial teeth. Our results provide quantitative support for the conjecture that chemotherapy alone is likely to have a greater impact on reducing onchocerciasis transmission in endemic areas where the main vector has a toothed fore-gut than in foci where the vectors have unarmed cibaria.

Africa, Western↗

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↗

Vector competence of Simulium metallicum s.l. (Diptera: Simuliidae) in two endemic areas of human onchocerciasis in northern Venezuela.

Experimental infections of Simulium metallicum s.l. with Onchocerca volvulus were carried out in two onchocerciasis foci, Altamira and Trincheras, in northern Venezuela, to determine vector competence. Wild-caught flies, fed on infected volunteers, were maintained in the laboratory for 13-15 days at 27 degrees C. Parasite development was complete but asynchronous and retarded. No differences in the vector competence of the two populations of S. metallicum s.l. were found. However, a less efficient development of the parasite occurred during the dry season at both localities. The distribution of the parasite within the vector was aggregated and also displayed seasonal variation. The seasonal susceptibility may be a consequence of a density-dependence regulation mechanism of the parasite within the vector. These results indicate a relatively low vector competence for S. metallicum s.l. in northern Venezuela.

Animals↗

Low level ivermectin coverage and the transmission of onchocerciasis.

Regular collections of biting Simulium damnosum s.l. were carried out during a community-based trial of doses of ivermectin every 6 months for onchocerciasis in Sierra Leone. Over 64,000 blackflies were caught at 4 sites close to treated villages and one site near an untreated village. More than 17,000 of these blackflies were dissected during the 31 months of the study and 5 doses of ivermectin were distributed to about 30% of the human population in the treated villages. High annual biting rates (about 100,000 bites per year) and transmission potentials (about 5000 larvae per year) were found at all catching sites. Approximately 30% of parous blackflies carried Onchocerca volvulus larvae, and 8% had infective stage larvae. None of these indices appeared to be affected by the distribution of ivermectin. However, the mean number of larvae per infected blackfly fell from 8.7 to 5.8 during the study period in the treated villages, equivalent to a 21% decrease per year. No such reduction was seen in the control village. This study demonstrates that in areas where high capacity vectors predominate, the effect on transmission of even a low coverage of the human population with repeated doses of ivermectin may be detectable using the sensitive entomological index of intensity of infection in infected flies. Statistical analysis of onchocerciasis transmission data is a complex issue and ways of improving the design of trials and applying appropriate statistical methods are discussed.

Animals↗

Occurrence and diagnosis of Mansonella streptocerca in Uganda.

During filaria surveys Mansonella streptocerca was found for the first time in Uganda, in 12 widely scattered villages in the Bundibugyo district between the Ruwenzori mountains and the Ituri forest, an area not endemic for Onchocerca volvulus. The crude prevalence in 806 examined adult persons ranged from 5 to 89% with an average of 61%. In 148 children the prevalence was 36%. The geometric mean of microfilaria (mf) densities in adult mf carriers was 1.7 mf/mg skin and the community microfilarial loads ranged from 1.0 to 13.7 mf/skin snip. In 476 persons skin snips from the shoulder contained mf in 58% and those from the buttocks in 48%. Skin snips from 68 persons digested with collagenase showed that only 30-37% of the mf emerged during 24 h incubation at 30 degrees C in isotonic salt solution. An itching acute or more often chronic papular dermatitis, predominantly on the upper parts of the body, was the typical skin lesion observed in 24% of 177 M. streptocerca mf carriers.

Adolescent↗

Models for the population biology and control of human onchocerciasis.

The absence of animal models in which to reproduce successfully the complete life cycle of Onchocerca volvulus has hindered progress towards unravelling the processes involved in the regulation of parasite abundance in the vertebrate host. Mathematical frameworks have been developed to explore the consequences of such processes in determining parasite population dynamics and the effect on these of control interventions. Post-control predictions are strongly influenced by the assumptions concerning the reproductive life span of the adult female worm (the longest-lived parasite stage) and the distribution of its survival times, and this notion is important to all frameworks. Here, we review the development of models concerning onchocerciasis and discuss the various approaches that have been used, presenting a deterministic framework with parameter values estimated from the Mexican onchocerciasis control programme. This model is used to evaluate interventions combining the removal of adult worms (nodulectomy) and the microfilaricidal and possibly sterilizing effect of ivermectin.

Animals↗

Ivermectin influence on the mast cell activity in nodules of onchocerciasis patients.

Onchocercal nodules were stained immunohistochemically using antibodies specific for human mast cells and IgE to elucidate the localization and frequency of mast cells after a single oral dose of 150 microg/kg ivermectin. Tryptase-and chymase-positive mast cells occurred predominantly in mixed inflammatory infiltrates and perivascularly, and never adhered to adult worms or microfilariae. Up to three days after ivermectin, mast cells and IgE-positive cells were markedly increased in the capsular area of nodules containing female worms with embryos and microfilariae compared to untreated nodules. In the centre of these nodules, around the adult Onchocerca volvulus, we found many tryptase-positive cells. More mast cells were IgE-positive than in untreated nodules, equalling the number of tryptase-positive mast cells. There was a clear correlation between the appearance of mast cells and the attacks on damaged microfilariae by eosinophils and macrophages and in the vicinity of adult worms by neutrophils that occur soon after ivermectin treatment. Onchocercomata harbouring female worms with oocytes only revealed, after all treatment intervals, the same mast cell numbers as untreated nodules. In conclusion, during the first three days after administration, ivermectin produces increased numbers of mast cells in nodules harbouring females with embryos and microfilariae, probably as part of an allergic reaction to the attacked microfilariae. Four to 19 days after ivermectin the number of mast cells in the entire nodule is no longer elevated.

Animals↗

Molecular phylogenetics of blackflies of the Simulium damnosum complex and cytophylogenetic implications.

The molecular phylogenetics of the Simulium damnosum complex, including vectors of the human parasite Onchocerca volvulus, from various parts of Africa was studied and compared with results of cytogenetic analyses. The sequence data of mitochondrial 16s and nuclear ITS2 rDNA revealed that the complex comprises two main clades, roughly covering the more easterly and westerly African taxa, respectively. However, striking inconsistencies in the tree topologies turned up between the DNA fragments regarding the position of certain subcomplexes and species. The cytophylogenetic relationships are better reflected in the ITS2 tree where Simulium pandanophilum and Simulium mengense constitute a basal, Central African clade of the entire complex and are therefore suggested to be the chromosomal roots too. Further divisions and the corresponding biogeographic interpretations are discussed. Several species and cytoforms are placed within the system for the first time. The phylogenetic relationships within the complex do hardly correlate with host preferences or other behavioral and ecological characteristics.

Animals↗

Human onchocerciasis in the lower Jos Plateau, central Nigeria: the prevalence, geographical distribution and epidemiology in Akwanga and Lafia local government areas.

An investigation of human infection with Onchocerca volvulus and the resulting clinical disease was carried out for the Nigerian National Onchocerciasis Control Programme between July and August 1989 [corrected]. The survey covered 10.6% of the rural population in 41 savanna villages of central Nigeria. Of the 8451 self-selected individuals examined, 900 (10.6%) had skin microfilariae (Mf). There were differences between villages in both endemicity and intensity of infection, but in general the number of both Mf carriers and cases of clinical onchocerciasis increased with age. The disease in the Mf carriers showed as blindness (0.8%), onchocercal nodules (0.6%), leopard skin (1.6%) and pruritus (2.8%). Of 35 persons with lymphatic complications, 19 had hanging groin, 10 had elephantiasis and six had hydrocoele. Onchocerciasis was mesoendemic in the rocky northern escarpments, and became hypoendemic and sporadic in the southern uplands of sedimentary geological origin.

Adolescent↗

Mast cells in onchocercomas from patients with hyperreactive onchocerciasis (sowda).

In onchocerciasis, variations of the host's immune responsiveness produce a spectrum of clinical manifestations ranging from the common generalized to the rare hyperreactive form (sowda). For further characterization of the immune response, the localization and frequency of mast cells in onchocercomas from untreated and ivermectin-treated patients with hyperreactive onchocerciasis from Liberia and the Yemen were analysed and compared to the generalized form by immunohistochemistry with antibodies specific for human mast cell tryptase and chymase, histamine and IgE. The nodules were selected with special regard to only one pair of live, microfilariae-producing Onchocerca volvulus. Throughout the nodular tissue of the hyperreactive form, mast cells accumulated in the strong inflammatory infiltrates, especially near eosinophils and around cellular attacks on microfilariae as well as perivascularly. Their number was significantly higher in the whole nodular tissue compared to the generalized form. The highest numbers occurred in the nodule centre. Mast cells carried IgE and appeared activated. No mast cells were observed in the cystic parts or attached to adult worms or microfilariae. In onchocercomas, 1 and 3 days after treatment with ivermectin, microgranuloma formation by eosinophils and macrophages around damaged microfilariae was enhanced and accompanied by numerous mast cells. Attacks of neutrophils were also pronounced, but attacks by mast cells were not observed. In conclusion, hyperreactivity against microfilariae in onchocercomas clearly correlates with a strong mastocytosis and IgE production parallel to tissue eosinophilia.

Adult↗

Immune responses directed against microfilariae correlate with severity of clinical onchodermatitis and treatment history.

The induction of pathological changes in Onchocerca volvulus infections is directly related to the presence of the microfilarial stage of this filarial nematode. Patients with either of the 2 major forms of the clinical disease (i.e., asymptomatic/mild [n=12] and severe [n=16] dermatopathology) were studied. The cellular immune responses (cell proliferation) of those with severe disease were stronger (stimulation index [SI], 12.3+/-1.9) than those with mild dermatopathological effects (SI, 2.9+/-0.6) or control patients (SI, 4.5+/-0.4). Cytoadherence antibody responses were greatest (grade 4) in the clinically severe group and only weak (grades < or = 1) in the mild group or the control patients. Ivermectin treatment was followed by an increase in immune responsiveness in those with initially poor responses. Thus, the degree of dermatopathological effect is related to the host's immune response against microfilariae, and ivermectin augments such responses.

Animals↗

Onchocerciasis in Taraba State, Nigeria: intensity, rate of infection and associated symptoms in 14 communities of Bali district.

An epidemiological study of 14 communities situated along the major road passing through Bali district in Taraba State, Nigeria, was carried out in continuation of a statewide filariasis survey which began in 1989. Of the 4,024 people that were examined for Onchocerca volvulus microfilaria and for clinical symptoms of the disease, onchocerciasis, an unusually low 13.3% prevalence rate was recorded with a range between 1.1% and 45.5%. Only one community had prevalence rate beyond 30.0%, six had infection rates between 10 and 29% while the remaining seven had less then 10% prevalence of the disease. However, infection was recorded in every community. The prevalence of physical symptoms was equally low. Pruritus was 7.3% and leopard skin was 0.4%. The prevalence of onchocerciasis increased with age in both male and female thus supporting the age and sex specific pattern of infection that had been reported in other parts of the state. A case is made for the continued prospection for onchocerciasis in the other districts of the state in order to identify and treat all communities that must benefit from the ongoing ivermectin treatment.

Adolescent↗

[The campaign against onchocerciasis in Africa: update].

Two methods are being used to control onchocerciasis. The first has a delayed effect and consists in reducing or interrupting transmission of Onchocerca volvulus by eradication of the vector at its most vulnerable developmental stage, i.e. the larval stage. The second method has more immediate effects and consists in mass treatment using ivermectin, the only widely available drug, to reduce the density of microfilariae (the pathogenic stage of the parasite) in the population. Both strategies have been implemented within the framework of two international programs: the Onchocerciasis Control Program (OCP) in West Africa, which started in 1974 and will continue until the end of 2002, and the African Program for Onchocerciasis Control (APOC), which was launched in 1995 and will last for 12 years. This article presents an overview of the efficacy of available control tools, as well as the objectives, strategies, organization, and results of the two ongoing control programs. Also dealt with are future perspectives of onchocerciasis control including monitoring techniques to maintain OCP gains, and research to develop new control tools and optimize the program efficacy.

Africa↗