Academic literature on the topic 'Onchocerciasis'

<p>Onchocerciasis, or river blindness, is a parasitic disease that affects more than 20 million people globally. The induction of pathology is directly related to the presence and destruction of the microfilarial stages (mf) of this filarial nematode. The disease presents clinically with a wide spectrum of dermal and ocular manifestations, the basis of the variation is believed to involve the immune system. The clinical presentations of infected hosts relate to the intensity of the reactions against the parasite. Anti-microfilarial drugs are also thought to somehow involve the immune system in their pharmacological action. In this study we have investigated some of the factors that might contribute to the pathogenesis, with the aim of gaining a better understanding of the role of immune response in these host inflammatory reactions to <i>Onchocerca volvulus</i> parasite. In the first study we have highlighted the clinically most severe form of dermal onchocerciasis, known as reactive onchocercal dermatitis (ROD), one that is often ignored and has not been properly identified. This form has special characteristics and important biological information that could greatly assist the general understanding of the disease as a whole. Amongst the three major foci of the disease in the study country, Sudan, the prevalence of ROD was found to be associated with different environmental and epidemiological characteristics; strikingly higher in the hypo-endemic areas. Including ROD cases in the prevalence will upgrade the level of endemicity of a locality, and often bring patients much in need of treatment into mass treatment programs that currently only treat localities with medium to high levels of endemicity. In the following research studies, we tried to address the immunological characteristics of the clinically different onchocerciasis patients. Then we also investigated the role of genetic polymorphism in the gene encoding receptor that links innate and adaptive immunity, namely, FcγRIIa.</p><p>Patients with either of two major forms of the clinical spectrum-mild and severe dermatopathology were studied by assaying the antigen-driven proliferation of peripheral blood mononuclear cells and the ability of patients’ serum antibodies to promote cytoadherence activity to mf <i>in vitro</i>. Immune responses of those with severe skin disease were found to be stronger compared with the mild dermatopathology group. Mectizan® treatment was followed by an increase in immune responsiveness in those with initially poor responses. Thus the degree of dermatopathology is related to the host’s immune response against mf and immunocompetence may be necessary for Mectizan® to clear the infection efficiently.</p><p>The infection has also been associated with increased levels of circulating immune complexes (CIC) containing parasite antigens and a cytokine response that involves both pro-and anti-inflammatory cytokines. Our fourth paper investigated the effect of IC from the <i>O. volvulus</i> infected patients on the production of pro-and anti-inflammatory cytokines. CIC were increased in all patients studied. The precipitate from plasma treated with polyethylene glycol (PEG) were added to peripheral blood mononuclear cell (PBMC) cultures, and the levels of IL-10, tumor necrosis factor TNF-α, IL-1β and their endogenous antagonists soluble TNF-Rp75 and IL-1-receptor antagonist (IL-1ra) were measured. A significant induction of all cytokines measured occurred in the onchocerciasis patients compared to healthy controls. However, the IL-1ra level was suppressed. The suppression of the production of IL-1ra suggests that the IC containing antigens may have a selectively suppressive effect on the production of this anti-inflammatory cytokine; thus implicating its possible role in counteracting inflammatory responses associated with the disease, and suggesting a potential therapeutic significance. </p><p>FcgRIIa receptors are involved in many important biological responses, and considered as important mediators of inflammation. A polymorphism in the gene encoding this receptor, that is either arginine (R) or histidine (H) at position 131, affects the binding to the different IgG subclasses. We therefore hypothesized that this polymorphism might be one of the underlying mechanisms to the varied clinical presentations seen in this disease. FcgRIIa genotyping was carried out by gene specific polymerase chain reaction (PCR) and allele-specific restriction enzyme digestion of DNA from clinically characterized patients. The genotype R/R frequencies were found to be significantly higher among patients with the severe form of the disease (including ROD), and it was particularly associated with one tribe (Masaleet) compared to Fulani. Moreover, the H allele was found to be associated with lower risk of developing the severe form. As no significant difference was seen between onchocerciasis cases and controls, the study also implies that this polymorphism influences protection from developing the severe form rather than being related to protection from the infection. </p>

Onchocerciasis, commonly known as "River blindness" is a disease affecting over 37 million people, worldwide. It is caused by the parasitic nematode Onchocerca volvulus and transmitted by the blackfly vector of the genus Simulium. The drug ivermectin (IVM) is the principal means of controlling the disease. As a result of recent reports on sub-optimal response to ivermectin and genetic selection in O. volvulus, we carried out a 21 month epidemiological study to investigate the response of O. volvulus to repeated rounds of IVM treatments in 2501 subjects from 19 Ghanaian communities that have received between 6 and 18 annual treatments and one IVM naive community. Skin microfilaria (mt) assessments were done before IVM treatment and at days 30, 90, 180 and 364 post-IVM treatment. At day 90 after the second IVM treatment, nodulectomies were carried out on 140 patients and embryogrammes constructed on female worms. We found IVM is still an effective microfilaricide, with efficacy of 98-100%. However, its effect on adult worm fertility has been reduced. Day 90 and 180 post-treatment showed significantly higher (p&lt;0.05) skin mf repopulation of 7.1% to 53.9%, and >100% of pretreatment counts at day 364 post-treatment in four communities compared with the other six communities, which had &lt;80% of pretreatment mf counts on day 364. From these results we classified the 10 communities into good IVM response (four communities), intermediate IVM response (two communities), poor IVM response (three communities), and the previously IVM naive community. Nodule and worm viability and worm densities were significantly higher (p&lt;0.05) in the poor response communities compared with the good response communities, with the intermediate falling between the two. Embryogramme analysis showed significantly higher reproductive activity and output in worms from poor response communities with up to 41% of females having live stretched mf in utero compared with good response communities which had no intra-uterine stretched mf. These results show evidence of lack of sustained response of adult O. volvulus to IVM in the poor response communities, manifested as a rapid return to fertility after IVM treatment. We conclude that IVM resistance is emerging in onchocerciasis and is manifested as a loss of effect of IVM on suppression of parasite reproduction.<br>Beta tubulin isotype 1 gene has been shown to be linked to IVM treatment and selection in O. volvulus and veterinary nematodes. Genetic analysis of the full length genomic DNA sequence of beta-tubulin from worms obtained in the three IVM response categories and IVM naive community showed single nucleotide polymorphisms (SNPs) at 24 sites on the entire 3696 bp. The frequencies of eight SNPs were significantly different (p&lt; 0.05) between the poor response communities and the good response/naive communities. Four SNPs, 183 T/G, 1188 T/C, 1309 CIT and 1545 A/G resulting in a genotype configuration GG/CC/TT/GG (183/1188/1309/1545) was significantly higher in the poor IVM response communities than the other communities. The phenotypic and genotypic analyses are consistent with a conclusion that IVM resistance has been selected. These four SNPs could be used to develop a genetic marker for early detection of IVM resistance. This study has shown for the first time that IVM resistance is emerging in Onchocerca volvulus and that there are genetic changes associated with IVM resistance which could be used for epidemiological monitoring for emerging resistance.