Background There is anecdotal evidence that ivermectin may decrease the frequency of seizures in Onchocerca volvulus-infected persons with epilepsy (PWE). Methods In October 2017, a 12-month clinical trial was initiated in rural Democratic Republic of Congo. PWE with onchocerciasis-associated epilepsy with ≥2 seizures/month were randomly allocated to receive over a one year period, ivermectin once or thrice (group 1), while other onchocerciasis-infected PWE (OIPWE) were randomized to ivermectin twice or thrice (group 2). All participants also received anti-epileptic drugs (AED). Study outcomes included seizure freedom during the last four months (primary endpoint), decrease in microfilarial density, and occurrence of adverse events. A multiple logistic regression model was used to evaluate the primary outcome. Results Of the 197 OIPWE enrolled, 100 were randomized to receive ivermectin thrice, 52 twice, and 45 once. In an intent-to-treat combined analysis of data from group 1 and 2, the probability to become seizure-free for OIPWE treated with ivermectin twice per year was significantly higher than in those treated once (OR: 5.087, 95% CI: 1.378-19.749; p=0.018) and individuals who received ivermectin twice had a 4.471 (95% CI: 0.944-6.769, p=0.075) times higher odds of seizure freedom than those received ivermectin once per year. Absence of microfilariae during the last 4 months was associated with a higher probability of seizure freedom (p=0.027). Conclusions Increasing the number of ivermectin treatments per year was found to suppress both microfilarial density and seizure frequency in OIPWE, suggesting that O. volvulus infection plays an etiological role in causing seizures. Registration: www.clinicaltrials.gov; NCT03852303

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 5 years. The global burden of onchodermatitis is progressively reducing and is no longer seen in children in many formerly endemic foci.

In South Sudan, three case-control studies found a positive association between Nodding Syn-drome (NS) and a Mansonella perstans infection. To investigate whether M. perstans could play the primary and sole causal role in the development of NS, we examined blood films of persons with and without epilepsy in rural villages affected by NS in Mahenge, Tanzania, to identify M. perstans infections. Study participants were also examined for onchocercal nodules and skin lesions and tested for the presence of anti-O. volvulus antibodies (Ov16 ELISA). One hundred and thirteen epilepsy cases and 132 controls were enrolled, with a mean age of 28.3 years (interquartile range 22 – 34 years); 125 (51%) were females. Of the persons with epilepsy, 43 (38.1%) met the probable NS criteria. M. perstans infection was absent in all participants, but Ov16 prevalence and oncho-cerciasis-associated skin manifestations were positively associated with epilepsy, including probable NS. Onchocercal nodules in the mothers of cases were also positively associated with epilepsy. In conclusion, in contrast with O. volvulus, M. perstans is likely not endemic in Mahenge and therefore cannot be a co-factor for NS in the area. Hence, this filaria cannot be the primary and sole causal factor in the development of NS.

A two phase survey of epilepsy was conducted in selected villages in Mundri West and East Counties (26 June−8 July, 2021), an onchocerciasis-endemic area in Western Equatoria State in South Sudan. In the first phase, households were visited by a trained research team to identify persons suspected to have epilepsy. In the second phase, persons suspected to have epilepsy were interviewed and examined by a clinician to confirm the diagnosis. A total of 364 households agreed to participate in the survey, amounting to 2,588 individuals. The epilepsy screening questionnaire identified 91 (3.5%) persons suspected to have epilepsy, of whom in 86 (94.5%) the diagnosis of epilepsy was confirmed by a clinician. The overall prevalence of confirmed epilepsy was 3.3% (95% CI: 2.7-4.1%), and of nodding syndrome 0.9% (95% CI: 0.6-1.4%). In 61 (16.8%) households there was at least one person with epilepsy. Only 1,212 (46.9%) of 2,583 people took ivermectin during the last distribution round in 2021. The annual epilepsy incidence was 77.3/100.000 (95% CI: 9.4-278.9/100,000) and the annual epilepsy mortality 251.2/100,000 (95% CI: 133.8-428.7/100,000). In conclusion, a high prevalence and incidence of epilepsy was observed in villages in Mundri. Urgent action is needed to prevent children from developing onchocerciasis-associated epilepsy by strengthening the local onchocerciasis elimination programme.

In June 2020, a door-to-door household survey was conducted in Mvolo County, an onchocerciasis endemic area in South Sudan. A total of 2,357 households containing 15,699 individuals agreed to participate in the study. Of these, 5,046 (32.1%, 95%CI: 31.4-32.9%) had skin itching and 445 (2.8%, 95% CI: 2.6-3.1%) were blind. An epilepsy screening questionnaire identified 813 (5.1%) persons suspected to have epilepsy. Of them, 804 (98.9%) were seen by a medical doctor and in 798 (98.1%) the diagnosis of epilepsy was confirmed. The overall epilepsy prevalence was 50.8/1000 (95% CI: 47.6-54.4/1000) and prevalence of nodding syndrome was 22.4/1000 (95% CI: 20.1-24.9/1000). Younger age, being male, skin itching, blindness and living in a village close to the Naam river were risk factors for epilepsy. The annual incidence of epilepsy was 82.8/100,000 (95% CI: 44.1-141.6/100,000). In conclusion, a high prevalence and incidence of epilepsy was observed in Mvolo, South Sudan. Strengthening the onchocerciasis elimination programme is urgently needed to prevent epilepsy in this region.

Onchocerciasis volvulus is the second highest infectious cause of blindness in the world, and is estimated to affect 37 million people, of whom 99% reside in sub-Saharan Africa. As a public health problem the disease is most closely associated with Africa, where it constitutes a serious obstacle to socio-economic development. Using the human ecology triad, this paper evaluates the dynamic interplay of population, habitat and behavioural factors in predicting perceived exposure to onchocerciasis among coastal inhabitants in Tanzania. Generalized linear models with log-log link function were fitted to cross-sectional survey data on 1253 individuals in three contiguous coastal regions. A significant proportion of respondents (28%) perceived that they were exposed to onchocerciasis. Residents in urban locations irrespective of wealth status were less likely to report living in onchocerciasis endemic environment compared with their rural counterparts. This is understandable given that urban areas of Tanga and Dar es Salaam are definitely non-endemic and perceived risk of onchocerciasis is related to the fact of living in an endemic area with active onchocercasis transmission. Individuals who had attained secondary (OR=0.51, p<0.01) or tertiary education (OR=0.37, p<0.001), and reported easy access to health facility (OR=0.53, p<0.001) were all less likely to report perceived exposure to onchocerciasis. This is not surprising because higher level of education and easy access to health facilities are characteristics of urban compared with rural areas. Policy implications suggest the need for the Tanzanian national neglected tropical disease control programme (TZNTDCP) to intensify health and educational campaigns at the community level and address susceptibility of vulnerable populations to the disease especially, for rural dwellers.

A deterministic compartment model for the transmission dynamics of onchocerciasis with nonlinear incidence functions in two interacting populations is studied. The model is quantitatively analyzed to investigate it's local asymptotic behavior with respect to disease-free and endemic equilibria. It is shown, using Routh-Hurwitz criteria, that the disease-free equilibrium is locally asymptotically stable when the basic reproduction number is less than the unity. When the reproduction number is greater than the unity, we prove the existence of a locally asymptotically stable endemic equilibrium. Furthermore, bifurcation analysis was done by investigating the possibility of the co-existence of the equilibria of the model at R0<0 but near R0=0 by Center Manifold Theory.

Despite of over 20 years of community directed treatment with ivermectin (CDTI), a high prevalence of onchocerciasis and onchocerciasis-associated epilepsy were observed in rural villages in Mahenge, Tanzania. Therefore, we assessed the knowledge, attitude and practice about onchocerciasis in four rural villages in the Mahenge area. This was a qualitative study conducted between June and July 2019. Eleven focus group discussions were organized with persons with epilepsy and their caretakers, community resource persons, and community drug distributors (CDDs), and two in-depth interviews with district programme coordinators of neglected tropical diseases (NTD). Most participants were aware about symptoms of onchocerciasis using local terminologies such as “ukurutu/rough dry skin” and “kuwashwa/itching”. A small proportion of people did not take ivermectin during CDTI for fear of adverse reactions such as itching and swelling. Some men believed that ivermectin may decrease libido. Challenges for high CDTI coverage included, long walking distance by CDDs to deliver drugs to households, persons being away for farming, low awareness of the disease and limited supervision by the NTD coordinators. In conclusion, ivermectin uptake in Mahenge should be optimised by continuous advocacy about the importance of taking ivermectin to prevent onchocerciasis-associated morbidity and by improving supervision during CDTI.

Onchocerciasis treatment and control relies mainly on the use of ivermectin which has high activity against the microfilarial stage of Onchocerca volvulus but limited activity against the long lived, tissue dwelling adult nematodes. As this neglected tropical disease has now been targeted for elimination there is an urgent need for new drugs to combat these parasites, ideally with macrofilaricidal activity. In this study we have examined the anti-Onchocerca activity of a range of existing FDA approved drugs with a view to repurposing, which can lead to rapid and relatively inexpensive development. From the Pharmakon-1600 library, 106 drugs were selected and tested against O. gutturosa adult male parasites using a concentration of 1.25 x 10-5 M in an in vitro 5-day standard assay to assess motility and viability (using MTT/formazan colorimetry). The findings revealed that 44 drugs produced marginal/moderate activity (50-99% motility and/or MTT reductions) including cefuroxime sodium, methenamine, primaquine phosphate, rivastigmine tartrate, while 23 drugs produced good activity (100% motility reductions and significant MTT reductions), including atovaquone, isradipine, losartan, rifaximin, cefaclor and pyrantel pamoate. Although this study represents only a first step, some of the identified hits indicate there are potential anti-Onchocerca drug candidates worthy of further investigation.

(1) Background: Newer generation ophthalmologists practicing in the developed world are not very familiar with some tropical ocular diseases due to the absence of reports in the ophthalmic literature over the past thirty years. Because of world globalization or due to influx of immigrants from Sub Saharan Africa, exotic retinal diseases are being encountered more often in ophthalmology clinics; (2) Methods: Case series of chorioretinitis or optic neuritis with obscure etiology; (3) Results: 4 cases qualified with the diagnosis of ocular onchocerciasis based on their residence near fast rivers in endemic areas, multimodal imaging, long term follow-up showing progressive disease and negative workup for other diseases. Characteristic findings include peripapillary choroiditis with optic neuritis or atrophy, subretinal tracts of the microfilaria, progressive RPE atrophy around heavily pigmented multifocal chorioretinal lesions of varying shapes and subretinal white or crystalline dots. Typical skin findings are often absent in eyes with chorioretinitis rendering the diagnosis more challenging; (4) Conclusions: Familiarity with the myriad ocular findings of onchocerciasis, and a high degree of suspicion in subjects residing in endemic areas can help in the correct diagnosis and implementation of appropriate chemotherapy. Onchocercid chorioretinitis is a slow insiduous progressive and prolonged polymorphous disease.