An ontology for immune epitopes: application to the design of a broad scope database of immune reactivities

BACKGROUND: Epitopes can be defined as the molecular structures bound by specific receptors, which are recognized during immune responses. The Immune Epitope Database and Analysis Resource (IEDB) project will catalog and organize information regarding antibody and T cell epitopes from infectious pathogens, experimental antigens and self-antigens, with a priority on NIAID Category A-C pathogens () and emerging/re-emerging infectious diseases. Both intrinsic structural and phylogenetic features, as well as information relating to the interactions of the epitopes with the host's immune system will be catalogued. DESCRIPTION: To effectively represent and communicate the information related to immune epitopes, a formal ontology was developed. The semantics of the epitope domain and related concepts were captured as a hierarchy of classes, which represent the general and specialized relationships between the various concepts. A complete listing of classes and their properties can be found at . CONCLUSION: The IEDB's ontology is the first ontology specifically designed to capture both intrinsic chemical and biochemical information relating to immune epitopes with information relating to the interaction of these structures with molecules derived from the host immune system. We anticipate that the development of this type of ontology and associated databases will facilitate rigorous description of data related to immune epitopes, and might ultimately lead to completely new methods for describing and modeling immune responses

No Evidence Known Viruses Play a Role in the Pathogenesis of Onchocerciasis-Associated Epilepsy. An Explorative Metagenomic Case-Control Study.

Despite the increasing epidemiological evidence that the Onchocerca volvulus parasite is strongly associated with epilepsy in children, hence the name onchocerciasis-associated epilepsy (OAE), the pathophysiological mechanism of OAE remains to be elucidated. In June 2014, children with unprovoked convulsive epilepsy and healthy controls were enrolled in a case control study in Titule, Bas-Uélé Province in the Democratic Republic of the Congo (DRC) to identify risk factors for epilepsy. Using a subset of samples collected from individuals enrolled in this study (16 persons with OAE and 9 controls) plasma, buffy coat, and cerebrospinal fluid (CSF) were subjected to random-primed next-generation sequencing. The resulting sequences were analyzed using sensitive computational methods to identify viral DNA and RNA sequences. Anneloviridae, Flaviviridae, Hepadnaviridae (Hepatitis B virus), Herpesviridae, Papillomaviridae, Polyomaviridae (Human polyomavirus), and Virgaviridae were identified in cases and in controls. Not unexpectedly, a variety of bacteriophages were also detected in all cases and controls. However, none of the identified viral sequences were found enriched in OAE cases, which was our criteria for agents that might play a role in the etiology or pathogenesis of OAE

Risk factors for epilepsy in Bas-Uélé Province, Democratic Republic of the Congo: a case–control study

Background: The reason for the high prevalence of epilepsy in onchocerciasis endemic areas remains unknown. The aim of this study was to detect risk factors associated with epilepsy in a region endemic for onchocerciasis. Methods: In June 2014, a case–control study was performed in Titule, Bas-Uélé Province in the Democratic Republic of the Congo. Individuals with unprovoked convulsive epilepsy of unknown aetiology were enrolled as cases (n = 59). Healthy members of families without cases of epilepsy in the same village were recruited as controls (n = 61). A multivariate binomial logistic regression analysis was performed to identify potential risk factors associated with epilepsy. To evaluate the potential protective effect of ivermectin treatment on the development of epilepsy, a nested age-matched case–control study was performed including only those who were eligible for ivermectin treatment in the year before they developed epilepsy. Results: Suspected onchocerciasis skin lesions were more often present in cases than in controls: 12/41 (29%) vs. 1/56 (2%), respectively (odds ratio (OR) 20.26, 95% confidence interval (CI) 2.42–170; p < 0.01). Ivermectin had been taken 7 months earlier in 29/59 (49%) cases and 29/61 (48%) controls. Onchocerca volvulus (OV) DNA was detected by PCR in skin snips in 26/34 cases (76%) and 10/14 controls (71%) (p = 0.7), and there was presence of OV IgG4 antibodies in 35/48 (73%) cases and 15/18 (83%) controls (p = 0.5). OV DNA was not detected in the cerebrospinal fluid of cases (controls not tested). Both cases and controls reported frequent bites by blackflies (Diptera, Simuliidae). Bathing daily as opposed to less often (OR 16.7, 95% CI 2.2–125.8; p < 0.01), bathing between 11 a.m. and 4 p.m. (OR 12.7, 95% CI 1.6–103.7; p = 0.02), and washing clothes between 11 a.m. and 4 p.m. (OR 10.9, 95% CI 1.5–77.3; p = 0.02) were all independently associated with epilepsy. Blood screening by specific PCR tests for Toxoplasma and Wuchereria bancrofti was negative in all cases and controls. A Loa loa infestation was found in only one case and one control by PCR and Giemsa smear. Antibodies to Taenia solium, Toxocara, and Trypanosoma sp were not detected in any of the participants. In an age-matched case–control analysis, 16/18 (89%) cases had not taken ivermectin the year before they developed epilepsy, compared to 7/18 (39%) controls that same year (p = 0.002). Conclusions: These data suggest that frequent activities at rivers known to be blackfly breeding sites and a historical lack of ivermectin treatment were risk factors for epilepsy in this onchocerciasis endemic area

Prevalence of River Epilepsy in the Orientale Province in the Democratic Republic of the Congo

An increased prevalence of epilepsy has been reported in many onchocerciasis endemic areas. To determine the prevalence and distribution of epilepsy in an onchocerciasis endemic region in the Democratic Republic of the Congo (DRC). An epilepsy prevalence study was carried out in 2014, in two localities of the Bas-Uélé district, an onchocerciasis endemic region in the Orientale Province of the DRC. Risk factors for epilepsy were identified using a random effects logistic regression model and the distribution of epilepsy cases was investigated using the Moran's I statistic of spatial auto-correlation. Among the 12,776 individuals of Dingila, 373 (2.9%) individuals with epilepsy were identified. In a house-to-house survey in Titule, 68 (2.3%) of the 2,908 people who participated in the survey were found to present episodes of epilepsy. Epilepsy showed a marked spatial pattern with clustering of cases occurring within and between adjacent households. Individual risk of epilepsy was found to be associated with living close to the nearest fast flowing river where blackflies (Diptera: Simuliidae)-the vector of Onchocerca volvulus-oviposit and breed. The prevalence of epilepsy in villages in the Bas-Uélé district in the DRC was higher than in non-onchocerciasis endemic regions in Africa. Living close to a blackflies infested river was found to be a risk factor for epileps

Nodding syndrome and epilepsy in onchocerciasis endemic regions: comparing preliminary observations from South Sudan and the Democratic Republic of the Congo with data from Uganda

BACKGROUND: Nodding syndrome (NS) is an epilepsy disorder occurring in children in South Sudan, northern Uganda and Tanzania. The etiology of NS is unknown, but epidemiological studies demonstrate an association between NS and onchocerciasis. METHODS: Between November 2013 and July 2015 we visited onchocerciasis endemic regions in South Sudan, Uganda, and the Democratic Republic of the Congo (DRC) to assess the epilepsy situation. In South Sudan we interviewed patients and affected families, health officials, colleagues and healthcare workers, and performed a small household survey to estimate the epilepsy prevalence in the village of Mvolo, Western Equatoria State. Most information from Uganda was collected through discussions with colleagues and a review of published literature and reports. In the Bas-Uélé district of the DRC, we visited the villages of Liguga, Titule and Dingila, interviewed patients with epilepsy and family members and conducted a preliminary entomological assessment. RESULTS: In South Sudan there is an ongoing NS and epilepsy epidemic in the Western Equatoria state that started around 1990. A survey of 22 households in Mvolo revealed that 28 out of 168 (16.7 %) children suffered from NS or another form of epilepsy. Thirteen (59 %) households had at least one child, and nine (41 %) households at least two children with NS or another form of epilepsy. In northern Uganda, an NS and epilepsy epidemic started around 2000. The occurrence of new NS cases has been in decline since 2008 and no new NS cases were officially reported in 2013. The decline in NS cases coincided with the bi-annual distribution of ivermectin and the treatment of blackfly-breeding rivers with larvicides. In Bas-Uélé district in the DRC, epilepsy appears to be endemic with cases clustered in villages close to blackfly-infested, rapid-flowing rivers. The majority of epilepsy cases in Liguga, Dingila and Titule presented with generalized (tonic–clonic) seizures without nodding, but with mental retardation. In Titule, an epilepsy prevalence of 2.3 % was documented. The only anthropophilic species of blackfly collected in the region belonged to the Simulium damnosum complex. CONCLUSION: Blackflies may play a key role in the transmission of an etiological agent that either directly or indirectly cause, not only NS, but also other forms of epilepsy in onchocerciasis endemic regions

Efficacy and safety of malarial prophylaxis with mefloquine during pregnancy in Kisangani, Democratic Republic of Congo: A randomized clinical trial

peer reviewedAims: Kisangani is an area with intense malaria transmission and sulfadoxine– pyrimethamine resistance. Alternative antimalaria prophylaxis medication and protocols are needed, particularly with pregnant individuals. In this study, we compare the tolerance and effectiveness of mefloquine regimen as a split dose with a meal vs. sulfadoxine–pyrimethamine for the intermittent preventive treatment in pregnant individuals in Kisangani. Methods: This study was conducted from 15 May to 30 November 2019 as a singleblind, randomized clinical trial comparing 2 regimens of intermittent preventive treatment during pregnancy. The first regimen consisted of 4 doses of sulfadoxine– pyrimethamine, and the second of 2 doses of mefloquine taken as a split dose with meal. Results: The occurrence of major or minor side-effects among patients treated with mefloquine and those treated with sulfadoxine–pyrimethamine were not statistically significant (major side effects: Fisher exact = 0.5014; minor side effects: P = 0.0961). Intermittent preventive treatment using mefloquine significantly reduced the risk of placental malaria (risk ratio [RR]: 0.4315, 95% confidence interval [CI]: 0.2201–0.8460), maternal peripheral parasitaemia (RR: 0.4397, 95% CI: 0.2377–0.8132) and low birth weight (RR: 0.4708, 95% CI: 0.2455–0.9029). Conclusion: Splitting dose and intake with a meal increased mefloquine tolerability while keeping its efficacy higher compared to sulfadoxine–pyrimethamine. Intermittent preventive treatment during pregnancy using mefloquine reduces the risk of placental malaria, maternal peripheral parasitaemia and low birth weight, compared to sulfadoxine–pyrimethamine. Thus, mefloquine is a good alternative to intermittent preventive treatment in pregnancy.DREPAKI