Gene/Protein Disease Symptom Drug Enzyme Compound
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River blindness (onchocerciasis) causes severe itching, skin lesions, and vision impairment including blindness. More than 99% of all current cases are found in sub-Saharan Africa. Fortunately, vector control and community-directed treatment with ivermectin have significantly reduced morbidity. Studies in Mali and Senegal proved the feasibility of elimination with ivermectin administration. The treatment goal is shifting from control to elimination in endemic African regions. Given limited resources, national and global policymakers need a rigorous analysis comparing investment options. For this, we developed scenarios for alternative treatment goals and compared treatment timelines and drug needs between the scenarios. Control, elimination, and eradication scenarios were developed with reference to current standard practices, large-scale studies, and historical data. For each scenario, the timeline when treatment is expected to stop at country level was predicted using a dynamical transmission model, and ivermectin treatment needs were predicted based on population in endemic areas, treatment coverage data, and the frequency of community-directed treatment. The control scenario requires community-directed treatment with ivermectin beyond 2045 with around 2.63 billion treatments over 2013-2045; the elimination scenario, until 2028 in areas where feasible, but beyond 2045 in countries with operational challenges, around 1.48 [corrected] billion treatments; and the eradication scenario, lasting until 2040, around 1.30 billion treatments. The eradication scenario is the most favorable in terms of the timeline of the intervention phase and treatment needs. For its realization, strong health systems and political will are required to overcome epidemiological and political challenges.
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PMID:Control, elimination, and eradication of river blindness: scenarios, timelines, and ivermectin treatment needs in Africa. 2595 Jan 77

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

Onchocerciasis is a neglected parasitic disease affecting the poorest underserved people in Yemen. A national control programme with goals to eliminate onchocerciasis has yet to be launched due to the current upheaval and social unrest in the country. The disease, locally termed as sowda, is unique in its clinicopathologic pattern, being of the localized, non-blinding, hyperreactive onchocercal skin disease. Although early reports identified endemic foci along seasonal watercourses, there is a need to redefine its epidemiologic patterns as well as health and socioeconomic impacts. Laboratory diagnosis of sowda among Yemeni patients is difficult due to the low load of microfilariae in skin snips and the presence of asymptomatic itching-free microfilaria carriers. Adoption of ivermectin use at three-month intervals as a control strategy has not been evaluated because the drug is mostly used in clinics and distributed to only a few affected communities. This paper addresses key aspects of onchocerciasis in Yemen and highlights the need for screening at-risk populations using highly sensitive techniques and mapping the distributions of the parasite in human and vector populations of blackflies. The new research should be integrated with the launch of a national onchocerciasis control programme to achieve onchocerciasis elimination.
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PMID:Onchocerciasis in Yemen: Time to take action against a neglected tropical parasitic disease. 2732 93

A community-directed treatment with ivermectin (CDTI) for fighting onchocerciasis was started in 2003 in the hyperendemic province of Bandundu, Democratic Republic of Congo (DRC); such initiative was supported by the African Programme for Onchocerciasis Control (APOC). As the APOC stopped at the end of 2015, there was an urgent need to assess the sustainability of an ivermectin treatment. A cross-sectional survey of knowledge, attitude and perception was conducted to determine the awareness level of local population regarding the disease. A multi-stage random sampling technique allowed the selection of 450 heads of households. Most respondents (96.9%) knew about onchocerciasis as a disease. The black-fly was viewed as the causing agent of onchocerciasis by 49.9% of respondents. The most commonly cited clinical manifestations were nodules (34.4%) and pruritus (31.1%), while blindness was the most frequently reported complication (90.7%). Approximately 55.1% of respondents had a good knowledge of onchocerciasis and CDTI. Overall, only 37% of participants had a favourable attitude and 46% a positive perception. Good knowledge was associated with school attendance (adjusted OR=1.9, 95%CI: 1.3-2.8, p=0.001), while education and continuation of treatment were related with good attitude (adjusted OR=9.7, 95%CI:4.8-19.5 and adjusted OR=19.8, 95%CI: 9.7-40.6, respectively, both with p<0.001). Good perception was associated with being at least 46 years old, non-Catholic and continuing the treatment (adjusted OR=3.2, 95%CI:1.2-9.1; adjusted OR=29.6, 95%CI:14.1-62.2 and adjusted OR=5.1, 95%CI:1.6-16.0 respectively, all with p<0.001). A good level of knowledge, attitude and perception is needed for a massive adherence of population to onchocerciasis control programmes. In the area of study (Moanza, DRC), good attitude and perception motivated the continuation of treatment in the population. In the future, different plans should focus on educational strategies to maintain a massive adherence and reduce onchocerciasis prevalence.
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PMID:Onchocerciasis in the Democratic Republic of Congo: Survey of knowledge, attitude and perception in Bandundu province. 2821 17

Onchocerciasis causes severe itching, serious skin disease and ocular damage leading to visual impairment or permanent blindness. It is associated with hanging groin, epilepsy, Nakalanga dwarfism and, most recently, nodding disease. This disease affected communities in 17 transmission foci in 37 districts of Uganda, where about 6.7 million people are once at risk. The efforts against onchocerciasis in Uganda commenced in the late 1940s, when vector control was launched using dichlorodiphenyltrichloroethane; by 1973, Simulium damnosum had been eliminated in the Victoria focus. Success outside of the Victoria focus was short-lived due to changes in government priorities and the political upheavals of the 1970s and 1980s. With the return of political stability, annual treatment with ivermectin through mass drug administration was launched in the early 1990s. Control of the disease has been successful, but there has been failure in interrupting transmission after more than 15 years. In 2007 Uganda launched a nationwide transmission elimination policy based on twice-per-year treatment and vector control/elimination, with a goal of eliminating river blindness nationwide by 2020. By 2017, 1 157 303 people from six foci had been freed from river blindness. This is the largest population ever declared free under World Health Organization elimination guidelines, providing evidence that elimination of river blindness in Africa is possible.
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PMID:After 70 years of fighting an age-old scourge, onchocerciasis in Uganda, the end is in sight. 2947 35

Loiasis is a vector-borne parasitic disease caused by the filarial nematode Loa loa and transmitted by the tabanid vectors from the genus Chrysops. Loa loa infection is associated with clinical manifestations such as pruritus, migratory transient edema, passage of adult worm in the bulbar conjunctiva, retinal damage, glomerular damage, albuminuria, pleural effusion, hydrocele, and endomyocardial fibrosis. Data reporting the occurrence of spontaneous encephalopathy associated with loiasis are very scanty. Severe adverse events occurring post-ivermectin administered in the framework of the fight against onchocerciasis and/or lymphatic filariasis in loiasis co-endemic areas have been closely associated with very high L. loa microfilariaemia. Different regimens have been used to lower L. loa microfilariaemia before definitive treatment, and many discrepancies have been reported. We report the case of a patient who was admitted to a health facility and hospitalized for 34 days for altered consciousness, blurred vision, headache, and chills. After other potential diagnoses were eliminated, the patient was confirmed with encephalopathy due to loiasis and referred to the Centre for Research on Filariasis and other Tropical Diseases (CRFilMT). On admission at CRFilMT, the patient was harboring 28,700 microfilariae per milliliter of blood (mf/mL), and after four 21-day courses of 400 mg daily albendazole, the L. loa microfilariaemia lowered to 5,060 mf/mL. The patient was then treated with ivermectin 3 mg and a total clearance of microfilariae was observed, with satisfactory clinical evolution and no adverse event. This case study further confirmed that albendazole is effective against L. loa, but might necessitate a longer course.
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PMID:Case Report: Probable Case of Spontaneous Encephalopathy Due to Loiasis and Dramatic Reduction of Loa loa Microfilariaemia with Prolonged Repeated Courses of Albendazole. 2974 Nov 49

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 causes debilitating pruritus and rashes as well as visual impairment and blindness. Prior to control measures, eye disease was particularly prominent in savanna areas of sub-Saharan Africa whilst skin disease was more common across rainforest regions of tropical Africa. Mass drug distribution with ivermectin is changing the global scene of onchocerciasis. There has been successful progressive elimination in Central and Southern American countries and the World Health Organization has set a target for elimination in Africa of 2025. This literature review was conducted to examine progress regarding onchocercal skin disease. PubMed searches were performed using keywords 'onchocerciasis', 'onchodermatitis' and 'onchocercal skin disease' over the past eight years. Articles in English, or with an English abstract, were assessed for relevance, including any pertinent references within the articles. Recent progress in awareness of, understanding and treatment of onchocercal skin disease is reviewed with particular emphasis on publications within the past five years. The global burden of onchodermatitis is progressively reducing and is no longer seen in children in many formerly endemic foci.
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PMID:Onchodermatitis: Where Are We Now? 3027 90

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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