Immunoinformatics Design and Assessment of a Multiepitope Antigen (OvMCBL02) for Onchocerciasis Diagnosis and Monitoring.

Onchocerciasis is a Neglected Tropical Disease that has a significant socioeconomic impact, especially in Sub-Saharan Africa. Numerous reports indicate that the Expanded Special Project for the Elimination of Neglected Tropical Diseases needs novel diagnostic tools before achieving its goal of successful elimination of onchocerciasis in Africa. The current diagnostic tests are either invasive, insensitive, or not applicable in the field and about 25% of persons infected cannot mount immune responses against the single antigen used in the only approved Ov-16 serological test. In the quest to identify novel biomarkers that can be used to certify that a patient is free from the disease, evaluate the progress of elimination programmes, and conduct post elimination surveillances, mass spectrometric analysis of Onchocerca volvulus crude extract revealed that 1392 proteins are expressed in the adult and microfilariae stages of the parasite. Computational analysis predicted six of the proteins as O. volvulus potential diagnostic targets. Linear B-epitopes were predicted from the six proteins and used to construct a multiepitope antigen (OvMCBL02). Serological analysis revealed that the OvMCBL02 test significantly differentiated between serum samples of onchocerciasis patients from the Kombone Health Area in the South West Region of Cameroon (n = 63) and control serum samples from Rwanda (n = 29) and Europe (n = 26) as well as between serum samples from the onchocerciasis hyperendemic region of Kombone Health Area (n = 63) and the hypoendemic region of Bandjoun Health District (n = 54). Interestingly, the test did not cross-react with serum samples from patients suffering from related nematode infections, thereby suggesting that further characterization of the OvMCBL02 multiepitope antigen will render it an additional member of the diagnostic toolbox for the elimination of onchocerciasis.

High prevalence of epilepsy in an onchocerciasis endemic health zone in the Democratic Republic of the Congo, despite 14 years of community-directed treatment with ivermectin: A mixed-method assessment.

OBJECTIVES: To investigate the reasons for the high prevalence of epilepsy (>6%) discovered in 2015 in the Aketi health zone in the north of the Democratic Republic of the Congo. METHODS: Persons with epilepsy (PWE) diagnosed in a door-to-door survey in 2015 were traced and re-examined in 2017 by a neurologist. Confirmed PWE were paired with matched controls. For onchocerciasis assessment, children 7-10 years old were tested for IgG4 Onchocerca volvulus (OV16) antibodies, a rapid epidemiological mapping of onchocerciasis (REMO) study was performed, and ivermectin coverage was investigated. RESULTS: Forty-three (61.4%) previously diagnosed PWE were traced; the neurologist confirmed the epilepsy diagnosis in all of them. The overall OV16 positivity rate was 64.5%. Poor ivermectin coverage (55.9%) and a high prevalence of onchocercal nodules (>70%) were observed. The prevalence of epilepsy was 5.7% in Aketi rural town, with nine PWE (13.8%) experiencing head nodding seizures. A case-control study showed that PWE had lower body weight and higher ivermectin coverage in 2017 than healthy controls. CONCLUSIONS: The high prevalence of epilepsy in the Aketi health zone, despite 14 years of community-directed treatment with ivermectin (CDTI), was found to be associated with high onchocerciasis transmission and low ivermectin use. An awareness programme to increase ivermectin coverage and the introduction of a bi-annual CDTI programme should be considered.

Report of the first international workshop on onchocerciasis-associated epilepsy.

BACKGROUND: Recently, several epidemiological studies performed in Onchocerca volvulus-endemic regions have suggested that onchocerciasis-associated epilepsy (OAE) may constitute an important but neglected public health problem in many countries where onchocerciasis is still endemic. MAIN TEXT: On October 12-14th 2017, the first international workshop on onchocerciasis-associated epilepsy (OAE) was held in Antwerp, Belgium. The workshop was attended by 79 participants from 20 different countries. Recent research findings strongly suggest that O. volvulus is an important contributor to epilepsy, particularly in meso- and hyperendemic areas for onchocerciasis. Infection with O. volvulus is associated with a spectrum of epileptic seizures, mainly generalised tonic-clonic seizures but also atonic neck seizures (nodding), and stunted growth. OAE is characterised by an onset of seizures between the ages of 3-18 years. Multidisciplinary working groups discussed topics such as how to 1) strengthen the evidence for an association between onchocerciasis and epilepsy, 2) determine the burden of disease caused by OAE, 3) prevent OAE, 4) improve the treatment/care for persons with OAE and affected families, 5) identify the pathophysiological mechanism of OAE, and 6) deal with misconceptions, stigma, discrimination and gender violence associated with OAE. An OAE Alliance was created to increase awareness about OAE and its public health importance, stimulate research and disseminate research findings, and create partnerships between OAE researchers, communities, advocacy groups, ministries of health, non-governmental organisations, the pharmaceutical industry and funding organizations. CONCLUSIONS: Although the exact pathophysiological mechanism underlying OAE remains unknown, there is increasing evidence that by controlling and eliminating onchocerciasis, OAE will also disappear. Therefore, OAE constitutes an additional argument for strengthening onchocerciasis elimination efforts. Given the high numbers of people with epilepsy in O. volvulus-endemic regions, more advocacy is urgently needed to provide anti-epileptic treatment to improve the quality of life of these individuals and their families.