Disease relevance of Onchocerciasis

• Using sera collected from onchocerciasis patients as a screening reagent, a cDNA clone (Ov39) has been isolated from a lambda gt11 expression library of Onchocerca volvulus [1].
• 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 [2].
• The rise in serum IL-5 before the posttreatment eosinophilia seen in this group of patients with onchocerciasis demonstrates a temporal relationship between IL-5 and the subsequent development of eosinophilia and implicates IL-5 as an important mediator of eosinophilia in humans [3].
• Proteinuria associated with diethylcarbamazine treatment of onchocerciasis [4].
• Suramin, a polysulfonated naphthylurea widely used in the treatment of trypanosomiasis and onchocerciasis, is currently being investigated as an antitumor agent for the treatment of advanced cancer [5].

High impact information on Onchocerciasis

• Comparison of ivermectin and diethylcarbamazine in the treatment of onchocerciasis [6].
• We therefore sought to determine whether antibodies produced by onchocerciasis patients might crossreact with the human 46-kD Ro/SS-A autoantigen (calreticulin) [2].
• 3. OC 3.6 produced a 152-kD beta-galactosidase fusion protein that was recognized in dot-immunoblots by 54 of 55 sera from onchocerciasis patients (98%) [7].
• 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 [8].
• BACKGROUND: In 1995, the World Bank launched an African Programme for Onchocerciasis Control to eliminate Onchocerca volvulus disease from 19 African countries by means of community-based ivermectin treatment (CBIT) [9].

Chemical compound and disease context of Onchocerciasis

• Suramin and eosinophil degranulation and vacuolation in onchocerciasis [10].
• 12 month follow-up of mebendazole therapy for onchocerciasis [11].
• Chloroquine and onchocerciasis [12].
• Chemotherapy of onchocerciasis: a controlled comparison of mebendazole, levamisole, and diethylcarbamazine [13].
• The results suggest that flubendazole is safer and more effective than DEC in the treatment of onchocerciasis [14].

Biological context of Onchocerciasis

• 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 [2].
• No cross-reaction occurred with sera from human schistosomiasis mansoni or onchocerciasis patients [15].
• The relationships between onchocercal infection, visual acuity and mortality have been examined using epidemiological data gathered by the Onchocerciasis Control Programme from 66 villages in West Africa. All of these villages were surveyed at least twice [16].
• Doxycycline in the treatment of human onchocerciasis: Kinetics of Wolbachia endobacteria reduction and of inhibition of embryogenesis in female Onchocerca worms [17].

Anatomical context of Onchocerciasis

• Interleukin-12 modulates T-cell responses to microfilariae but fails to abrogate interleukin-5-dependent immunity in a mouse model of onchocerciasis [18].
• Second, in the onchocerciasis patients, non-lymphoid cells of the conjunctiva and iris, such as vascular endothelium, pericytes and fibroblasts were in an activated state, as shown by increased expression of Class II MHC antigens (P less than 0.02, conjunctiva; P less than 0.05, iris) [19].
• Eotaxin and RANTES expression by the dermal endothelium is associated with eosinophil infiltration after ivermectin treatment of onchocerciasis [20].
• Autoantibodies against the endoplasmic reticulum (ER) luminal protein, calreticulin are often present in sera from patients with systemic lupus erythematosus, rheumatic disease and various parasitic diseases including onchocerciasis [21].
• Microfilariae in the cerebrospinal fluid, and neurological complications, during treatment of onchocerciasis with diethylcarbamazine [22].

Gene context of Onchocerciasis

• In contrast, PBMC from onchocerciasis patients clearly produced more IL-10 than did cells from endemic normals [23].
• The cutaneous T cell-attracting chemokine (CTACK/CCL27) was found highly elevated in onchocerciasis patients compared to infection-free European controls (P = 0.0004) and it did not change following ivermectin or placebo to 1 year post-therapy [24].
• The roles of eotaxin, RANTES, and MCP-3 expression in eosinophil recruitment to the site of parasite killing that occurs following ivermectin treatment of onchocerciasis were assessed in the skin of 13 Onchocerca volvulus-infected subjects and two noninfected controls before and after ivermectin treatment [20].
• Regulation of IL-5 in onchocerciasis. A critical role for IL-2 [25].
• These findings suggest that IL-2 production is required to induce IL-5 and further implicates IL-5 as a possible mediator of protection in onchocerciasis [25].

Analytical, diagnostic and therapeutic context of Onchocerciasis

• Double-blind study of ivermectin and diethylcarbamazine in African onchocerciasis patients with ocular involvement [26].
• 35S-methionine-labeled proteins of dog heartworm microfilariae (mf) were analyzed in immunoprecipitation assays by using a panel of sera drawn from humans diagnosed for onchocerciasis and from canines infected with D. immitis [27].
• Elevations in IL-6 correlated with the occurrence and severity of clinical symptoms after treatment; for the onchocerciasis patients IL-6 levels directly reflected pretreatment intensity of infection [28].
• Furthermore, none of the onchocerciasis sera tested recognized recombinant calreticulin by Western blot analysis [29].
• Serum levels of autoantibodies, directed against human S-antigen and interphotoreceptor retinoid-binding protein (IRBP), were determined in patients with onchocerciasis (n = 46) and endemic controls (n = 38) from Sierra Leone with the use of an enzyme immunoassay [30].

References