Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033774 (pruritus)
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Human onchocerciasis (river blindness), caused by the filarial nematode Onchocerca volvulus, has been successfully controlled by a single drug, ivermectin, for over 25 years. Ivermectin prevents the disease symptoms of severe itching and visual impairment by killing the microfilarial stage, but does not eliminate the adult parasites, necessitating repeated annual treatments. Mass drug administration with ivermectin does not always break transmission in forest zones and is contraindicated in individuals heavily co-infected with Loa loa, while reports of reduced drug efficacy in Ghana and Cameroon may signal the development of resistance. An alternative treatment for onchocerciasis involves targeting the essential Wolbachia symbiont with tetracycline or its derivatives, which are adulticidal. However, implementation of antibiotic therapy has not occurred on a wide scale due to the prolonged treatment regimen required (several weeks). In the bovine Onchocerca ochengi system, it has been shown previously that prolonged oxytetracycline therapy increases eosinophil counts in intradermal nodules, which kill the adult worms by degranulating on their surface. Here, in an "immunochemotherapeutic" approach, we sought to enhance the efficacy of a short, sub-lethal antibiotic regimen against O. ochengi by prior immunotherapy targeting onchocystatin, an immunomodulatory protein located in the adult female worm cuticle. A key asparagine residue in onchocystatin was mutated to ablate immunomodulatory activity, which has been demonstrated previously to markedly improve the protective efficacy of this vaccine candidate when used as an immunoprophylactic. The immunochemotherapeutic regimen was compared with sub-lethal oxytetracycline therapy alone; onchocystatin immunotherapy alone; a gold-standard prolonged, intermittent oxytetracycline regimen; and no treatment (negative control) in naturally infected Cameroonian cattle. Readouts were collected over one year and comprised adult worm viability, dermal microfilarial density, anti-onchocystatin IgG in sera, and eosinophil counts in nodules. Only the gold-standard antibiotic regimen achieved significant killing of adult worms, a profound reduction in microfilarial load, and a sustained increase in local tissue eosinophilia. A small but statistically significant elevation in anti-onchocystatin IgG was observed for several weeks after immunisation in the immunotherapy-only group, but the antibody response in the immunochemotherapy group was more variable. At 12 weeks post-treatment, only a transient and non-significant increase in eosinophil counts was apparent in the immunochemotherapy group. We conclude that the addition of onchocystatin immunotherapy to a sub-lethal antibiotic regimen is insufficient to induce adulticidal activity, although with booster immunisations or the targeting of additional filarial immunomodulatory proteins, the efficacy of this strategy could be strengthened.
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PMID:Immunotherapy with mutated onchocystatin fails to enhance the efficacy of a sub-lethal oxytetracycline regimen against Onchocerca ochengi. 2610 Jan 52

Onchocerciasis is a severe parasitic infestation caused by Onchocerca volvulus which causes disabling skin and subcutaneous tissue changes and ultimately leads to blindness. It has a huge public health impact due to its socioeconomic burden and the vast number of people it affects in developing countries. In this case, a 60 years old woman was encountered with leopard skin like changes, rashes and pruritus on the left leg; which had been managed as cutaneous mycosis for over a period of 8 years. A diagnosis of onchocerciasis was finally made after a skin snip identified onchocercal microfilariae. The above case shows that onchocerciasis is still a neglected tropical disease (NTD) in Cameroon. This emphasizes the need for more expansive outreach programs in remote areas in Cameroon, a change in health policies to ensure the eradication of this disabling disease and health promotion amongst vulnerable populations.
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PMID:Cutaneous onchocerciasis in Dumbu, a pastoral area in the North-West region of Cameroon: diagnostic challenge and socio-economic implications. 2696 94

The African Programme for Onchocerciasis Control (APOC), which focused on annual mass treatment with ivermectin, was launched in 1995 and was replaced by the Expanded Special Project for Neglected Tropical Diseases (ESPEN) by the end of 2015. In Ghana, the Community Directed Treatment with Ivermectin (CDTI) was introduced in 1999. After a decade, biannual reinforcement was introduced during which the Ghana Health Service (GHS) recorded coverage rates through routine data collection. Transmission studies conducted in the Upper Denkyira East Municipal (UDEM) of the forest zone of Ghana in 2002 and 2006 had shown that annual treatments with ivermectin had hardly any effect on the transmission of Onchocerca volvulus by the vector Simulium sanctipauli. In order to establish whether or not this was due to an insufficient compliance to the CDTI programme, an additional questionnaire survey was carried out in 2013 following those conducted in 2002 and 2006. The repeat transmission survey conducted in 2013 in the same area revealed that the vector S. sanctipauli had apparently disappeared from the rivers Ofin and Pra due to gold mining activities. In 2006 and 2013, we conducted surveys using structured questionnaires to address issues related to compliance and to compare results on the effectiveness of CDTI. A total of 692 individuals from 7 villages and 447 individuals from 9 villages were interviewed in 2006 and 2013 respectively. Questions asked included whether or not they had taken the ivermectin and reasons for not doing so when that was the case. Results were compared with the previous investigations conducted in 2002. Whereas official reported coverage rates ranged from 59 to 85% in 2006 and from 88 to 97% in 2013, compliance rates decreased from 36% in 2006 to 21% in 2013. Factors affecting compliance included fear of unpleasant side effects (pruritus and oedema), which decreased from 36% to 21% for the same period. Lack of awareness of CDTI sharply increased from 12% to 46% for the same period. Participants believed that treatments were no longer necessary due to the absence of vectors observed in 2013. There seems to be a considerable difference between coverage and compliance rates in the study communities. The difference can be attributed to the performance of the Community-Directed Distributors (CDDs) and the absence of the vector population observed in 2013. Discussions with CDDs suggested that factors that led to non-compliance were mostly side effects, unawareness of the disease by immigrants and lack of financial motivation for the CDDs. Also included was the fact that they needed to complete distribution of the drugs in the entire village, covering all households within just one week irrespective of the size of the catchment area. This, they thought was too much work for a short period of time. We propose to intensify the training of CDDs by the national Neglected Tropical Diseases Programme (NTDP) and to include the Community-based Health and Planning Services (CHPS) concept into onchocerciasis control efforts for awareness creation while the vector population and the transmission should be further monitored. The population should be made aware that the side effects they experienced from previous treatments or had heard about had reduced significantly. They also should be in the known that vector flies may return and so the risk of transmission remains.
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PMID:Evaluation of onchocerciasis control in the Upper Denkyira East municipal in the forest area of Ghana: Responses of participants and distributors to the CDTI programme. 2993 33

Onchocerciasis is a neglected tropical disease caused by a nematode parasite, Onchocerca volvulus, and transmitted by bites of Simulium blackflies which breed near fast-flowing rivers. In humans, thousands of microfilariae (immature worms) migrate to the skin and eyes where they cause pathology. Historically, much research was devoted to the serious effect of blindness, from which the disease earns its alternative name of 'river blindness'. Mapping the burden of onchocercal skin disease (OSD) was expedited by the development of a clinical classification and grading system that facilitated comparison of data from different countries. After successful field testing in Nigeria, the classification scheme was used in a multicountry study in seven endemic sites, to estimate the true burden of OSD across Africa. High levels of OSD were found, affecting 28% of the population. A new control programme, the African Programme for Onchocerciasis Control (APOC) was launched in 20 countries using annual doses of ivermectin, donated by Merck & Co., Inc. The multicountry study also found a close correlation between the levels of itching and OSD with the level of endemicity, as determined by the prevalence of onchocercal nodules. This enabled APOC to use Rapid Epidemiological Mapping of Onchocerciasis, which entailed identifying likely vector breeding sites near rivers, then sampling 50 adult males in nearby villages to determine the prevalence of nodules and delineate which villages required treatment. Onchocerciasis is now targeted for elimination in Africa, and the challenge is to complete Onchocerciasis Elimination Mapping of hypoendemic areas using serology.
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PMID:Mapping the burden of onchocercal skin disease. 3230 10


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