Recent research suggests that infection with Onchocerca volvulus induces neurocognitive decline. This study sought to compare the cognitive outcomes of elderly persons based on onchocerciasis infection status and report the overall prevalence of dementia in the rural Ntui Health District in Cameroon. A community-based approach was used to recruit 103 participants aged ≥60 years. Dementia screening was done using the Community Screening Interview for Dementia (CSID) tool with a cut-off value of ≤29.5. O. volvulus infection was determined via microscopic examination of skin snips and serological testing of Ov16 antibodies using rapid diagnostic tests. Overall, the prevalence of dementia was 10.7%. Among the tested individuals, 17.9% (15/84) and 62.1% (41/66) were positive for O. volvulus and Ov16 antibodies, respectively. A multivariable linear regression model of CSID scores found a significant positive association with education level (8.654; 95% CI: 2.0870 to 15.222). However, having a positive skin snip for O. volvulus (-3.399; 95% CI: -6.805 to 0.007) and inhaling tobacco (-5.441; 95% CI: -9.137 to -1.744) tended to lower the CSID scores. Ongoing onchocerciasis transmission in the Ntui Health District may constitute a risk factor for dementia. Strengthening onchocerciasis elimination and adopting healthier lifestyles would contribute to dementia prevention among the elderly residing in endemic communities.

BACKGROUND: Globally, there are an estimated 20.9 million cases of onchocerciasis, with Africa bearing the greatest burden. The World Health Organization (WHO) has targeted the disease for elimination by 2030. As of August 2023, there were 15 foci in 37/48 (76%) districts and one city in Uganda that had reached the elimination phase. However, there is a paucity of data on community involvement in post-elimination surveillance (PES) activities. The communities in the post-elimination phase are expected to maintain surveillance, provide health education, refer cases for treatment, and participate in surveillance. However, it is not clear whether this is being done. In this study, we assessed the feasibility of community involvement in post-elimination surveillance activities in Bududa District, Eastern Uganda, to draw key generalisable lessons for similar settings.
METHODS: This was a cross-sectional study employing rigorous mixed methods of data collection. We used a semi-structured questionnaire to collect quantitative data on randomly sampled study participants in two sub-countries in the district. Community involvement in post-elimination surveillance (PES) was our dependent variable, measured using Yes or No questions, and our independent variables were measured on different scales. Computations of proportions and associations were done using Stata 15 software. Conversely, qualitative data were collected via focus group discussions (FGDs) for community participants and key informant interviews (KIIs) for local leaders. For the qualitative component, we had 2 FGDs, each consisting of 8 gender-balanced participants per group and 8 KIIs. Qualitative data analyses were done using a robust thematic framework approach, ensuring the reliability and validity of our findings.
RESULTS: A total of 422 participants with a mean age of 51.4 years (SD = 15.8) participated in the study. Community involvement in post-elimination surveillance was low (14%). Factors associated with involvements were district support [Adjusted odd ratio AOR 14, 95 CI = (2.5, 81.7)], seeing black flies in the environment in a week preceding the survey [AOR 8, 95% CI = (1.5, 42.5)], in one month [AOR 3.8, 95% CI = (1.1, 13.2)], and being a community volunteer in the Ivermectin treatment program [AOR 4.3, 95% CI = (1.03, 17.9)]. Lack of funding, poor motivation, poor program sustainability planning, and a lack of drugs at health facilities were key challenges affecting community involvement in post-elimination surveillance.
CONCLUSIONS: Community involvement in onchocerciasis post-elimination surveillance activities in Bududa District in Eastern Uganda was low but could be improved by increased district support, funding, community motivation and sensitisation.

Besides being vectors of the onchocerciasis parasite, blackflies are a source of nuisance in onchocerciasis-endemic communities. We investigated the experience of residents in the Ntui Health District (Cameroon) regarding blackfly nuisance and assessed their perceptions of a novel \"Slash and Clear\" (S&C) intervention for blackfly control. Focus group discussions were conducted before and after S&C implementation (respectively, in February 2022 and December 2023). Blackflies were known to emerge from the river areas and cause disease. To prevent blackfly bites, the population often covered their body with protective clothing and applied various substances (kerosene, oil, or lemon) to their skin. Post-intervention data showed reduced blackfly nuisance, and the willingness to sustain blackfly control in the long-term was unanimous among community leaders and members, including the village volunteers who implemented the S&C intervention. In conclusion, blackfly nuisance is evident in the Ntui onchocerciasis focus of Cameroon and led to a panoply of coping practices, some of which could be detrimental to their health. Implementing S&C for blackfly control is well accepted and could sustainably alleviate the nuisance caused by blackflies while simultaneously breaking the onchocerciasis transmission cycle.

AWZ1066S has been developed as a potential treatment for the neglected tropical diseases lymphatic filariasis and onchocerciasis. AWZ1066S targets the Wolbachia bacterial endosymbiont present in the causative nematode parasites. This phase 1, first-in-human study aimed to assess the safety and pharmacokinetics of AWZ1066S in healthy human participants. In a randomized double-blind, placebo-controlled, single ascending dose study, healthy adults received a single oral dose of AWZ1066S (or placebo) and were followed up for 10 days. The planned single doses of AWZ1066S ranged from 100 to 1600 mg, and each dose was administered to a cohort of 8 participants (6 AWZ1066S and 2 placebo). In total 30 people participated, 18 (60%) female, median age 30.0 years (minimum 20, maximum 61). The cohorts administered 100, 200, 300, and 400 mg of AWZ1066S progressed unremarkably. After single 700-mg doses all 4 participants developed symptoms of acute gastritis and transient increases in liver enzymes. The severity of these adverse events ranged from mild to severe, with 1 participant needing hospital admission. Pharmacokinetic analysis indicated that AWZ1066S is rapidly absorbed with predictable pharmacokinetics. In conclusion, safety concerns prevented this study from reaching the human exposures needed for AWZ1066S to be clinically effective against lymphatic filariasis and onchocerciasis.

UNASSIGNED: Mvolo in Western Equatoria of South Sudan has been a hotspot for Onchocerca volvulus transmission since the 1940s. In Mvolo onchocerciasis is a disease of public health importance, associated with onchocerciasis-associated epilepsy including nodding syndrome.
UNASSIGNED: We conducted an entomological study to map the breeding sites of blackflies (Simulium damnosum, sensu lato) on the river Naam, to allow the removal of vegetation from vector breeding sites, the \"slash and clear\". Three blackfly catching sites were established along the river. Focus group discussions were also conducted to assess the willingness of the communities to support the \"slash and clear\" intervention and the semi-annual distribution of ivermectin.
UNASSIGNED: A total of 2466 female S. damnosum s.l. were caught in 14×11h (06.00-15.00) catches. The highest biting density of 4210.25 flies/month/h and monthly biting rate (MBR) of 11,482.25 bites/man/month were observed in November 2023. Biting density and MBR reduced to zero in the intervention site by April 2024. While the mean parity rate was 31% (CI: 0.2976±0.9176). Two diurnal biting peaks were observed, one from 9:00-10:00 (at the bridge site) and a prominent one from 14:00-15:00 in the two catching sites in Mvolo. Along the river Naam, only one site was found productive for S. damnosum s.l.; and the larvae and adults were morphologically associated with the anthropophilic S. damnosum. The \"slash and clear\" intervention was implemented at Dogoyabolu along the river Naam. Communities expressed willingness to support a \"slash and clear\" intervention and the semi-annual distribution of ivermectin.
UNASSIGNED: S. damnosum active breeding was identified along the river Naam in a stretch of 3-5 km close to human settlements. Highest blackfly biting density was 4210.25 flies/month/h, and two fly biting peaks were observed. A community \"slash and clear\" vector control was implemented, and will be prospectively monitored.

OBJECTIVE: The potential impact of cumulative community-directed treatment with ivermectin (CDTI) on epilepsy epidemiology in Mvolo County, South Sudan, an onchocerciasis-endemic area with high epilepsy prevalence, was investigated. Annual CDTI was introduced in 2002 in Mvolo, with interruptions in 2016 and 2020.
METHODS: Comprehensive house-to-house surveys in Mvolo (June 2020 and 2022) identified cases of epilepsy, including probable nodding syndrome (pNS). Community workers screened households in selected sites for suspected epilepsy, and medical doctors confirmed the diagnosis and determined the year of seizure onset. The incidence of epilepsy, including pNS, was analysed using 95% confidence intervals (CIs). Data on ivermectin intake and onchocerciasis-associated manifestations (itching and blindness) were collected.
RESULTS: The surveys covered 15,755 (2020) and 15,092 (2022) individuals, identifying 809 (5.2%, 95% CI: 4.8-5.5%) and 672 (4.5%, 95% CI: 4.1-4.8%) epilepsy cases, respectively. Each survey reported that a third of the surveyed population experienced skin itching, and 3% were blind. Epilepsy incidence per 100,000 person-years gradually declined, from 326.5 (95% CI: 266.8-399.1) in 2013-2015 to 96.6 (95% CI: 65.5-141.7) in 2019-2021. Similarly, pNS incidence per 100,000 person-years decreased from 151.7 (95% CI: 112.7-203.4) to 27.0 (95% CI: 12.5-55.5). Coverage of CDTI was suboptimal, reaching only 64.0% of participants in 2019 and falling to 24.1% in 2021 following an interruption in 2020 due to COVID-19 restrictions. Additionally, while 99.4% of cases had active epilepsy in 2022, less than a quarter of these had access to antiseizure medication.
CONCLUSIONS: The observed decrease in epilepsy incidence despite suboptimal CDTI coverage highlights the potential impact of onchocerciasis control efforts and underscores the need to strengthen these efforts in Mvolo County and across South Sudan. As a proactive measure, Mvolo and neighbouring counties are transitioning to biannual CDTI. Furthermore, the substantial epilepsy treatment gap in Mvolo should be addressed.

BACKGROUND: After ivermectin became available, diethylcarbamazine (DEC) use was discontinued because of severe adverse reactions, including ocular reactions, in individuals with high Onchocerca volvulus microfilaridermia (microfilariae/mg skin, SmfD). Assuming long-term ivermectin use led to < 5 SmfD with little or no eye involvement, DEC + ivermectin + albendazole treatment a few months after ivermectin was proposed. In 2018, the US FDA approved moxidectin for treatment of O. volvulus infection. The Phase 3 study evaluated SmfD, microfilariae in the anterior chamber (mfAC) and adverse events (AEs) in ivermectin-naïve individuals with ≥ 10 SmfD after 8 mg moxidectin (n = 978) or 150 µg/kg ivermectin (n = 494) treatment.
METHODS: We analyzed the data from 1463 participants with both eyes evaluated using six (0, 1-5, 6-10, 11-20, 21-40, > 40) mfAC and three pre-treatment (< 20, 20 to < 50, ≥ 50) and post-treatment (0, > 0-5, > 5) SmfD categories. A linear mixed model evaluated factors and covariates impacting mfAC levels. Ocular AEs were summarized by type and start post-treatment. Logistic models evaluated factors and covariates impacting the risk for ocular AEs.
RESULTS: Moxidectin and ivermectin had the same effect on mfAC levels. These increased from pre-treatment to Day 4 and Month 1 in 20% and 16% of participants, respectively. Six and 12 months post-treatment, mfAC were detected in ≈5% and ≈3% of participants, respectively. Ocular Mazzotti reactions occurred in 12.4% of moxidectin- and 10.2% of ivermectin-treated participants without difference in type or severity. The risk for ≥ 1 ocular Mazzotti reaction increased for women (OR 1.537, 95% CI 1.096-2.157) and with mfAC levels pre- and 4 days post-treatment (OR 0: > 10 mfAC 2.704, 95% CI 1.27-5.749 and 1.619, 95% CI 0.80-3.280, respectively).
CONCLUSIONS: The impact of SmfD and mfAC levels before and early after treatment on ocular AEs needs to be better understood before making decisions on the risk-benefit of strategies including DEC. Such decisions should take into account interindividual variability in SmfD, mfAC levels and treatment response and risks to even a small percentage of individuals.

BACKGROUND: In Ethiopia, Onchocerciasis is a prevalent neglected tropical disease, currently targeted for elimination with mass drug administration and community behavioral changes towards sustained control and eventual elimination. This study aimed to elucidate the awareness, perceptions and practices of endemic communities in Jimma Zone, Ethiopia.
METHODS: Community-based cross-sectional study triangulated with qualitative method was conducted from October-November, 2021. A multistage sampling was employed and data were collected using a pre-tested interviewer-administered structured questionnaire. Logistic regression was used to identify the predictors of comprehensive knowledge and preventive practice. Adjusted odds ratios were calculated at 95% confidence interval (CI) and considered significant with a p-value of <0.05. Kruskal-Whallis and Mann-whitney tests were used to compare median risk perception score by socio-demographic factors. Qualitative data were collected through focus group discussions and key informant interviews and transcribed verbatim. Then the data were coded, categorized, and themes were developed.
RESULTS: The overall prevalence of adequate comprehensive knowledge was 48.8% (95% CI: 44.9, 52.3), high risk perception was 18.7% (95%CI15.9, 21.4) and preventive practice was 46.9%(95%CI:(43.3,50.4). High risk perception[AOR = 1.95 95%CI: (1.32, 2.89] was statistically significant with comprehensive knowledge, likewise knowledge of mode of transmission [AOR = 2.64 95% CI: (1.44, 4.85)], knowledge of consequences [AOR = 2.12 95%CI: (1.21, 3.72)] and knowledge of preventive measures [AOR = 15.65,95%CI:(10.1, 24.2)] were statistically significant with preventive practice. The median risk perception was varied significantly between the groups by educational status, study district and age category. Qualitative evidence showed that there were great community knowledge gap about the disease.
CONCLUSIONS: Community knowledge, perceptions, and practices are unacceptably low. Risk perception was significantly associated with comprehensive knowledge, likewise knowledge of mode of transmission, consequences and preventive measures were significantly associated with preventive practice. This implies knowledge is a key component of effective prevention strategies as it is a necessary condition for the behavior change.

UNASSIGNED: A high prevalence of onchocerciasis-associated epilepsy (OAE) has been observed in onchocerciasis-endemic areas with high ongoing Onchocerca volvulus transmission. However, the pathogenesis of OAE remains to be elucidated. We hypothesise that the O. volvulus virome could be involved in inducing epilepsy. With this study, we aim to describe the O. volvulus virome and identify potential neurotropic viruses linked to OAE.
UNASSIGNED: In Maridi County, an onchocerciasis endemic area in South Sudan with a high prevalence of OAE, we will conduct an exploratory case-control study enrolling 40 persons aged 12 years and above with palpable onchocerciasis nodules. Cases will be participants with OAE (n=20), who will be age- and village-matched with controls without epilepsy (n=20). For each study participant, two skin snips at the iliac crest will be obtained to collect O. volvulus microfilariae, and one nodulectomy will be performed to obtain adult worms. A viral metagenomic study will be conducted on microfilariae and adult worms, and the O. volvulus virome of persons with and without OAE will be compared. The number, size, and localisation of onchocerciasis nodules in persons with and without OAE will be described. Moreover, the pre- and post-nodulectomy frequency of seizures in persons with OAE will be compared.
UNASSIGNED: The protocol has been approved by the Ethics Committee of the University of Antwerp and the Ministry of Health of South Sudan. Findings will be disseminated nationally and internationally via meetings and peer-reviewed publications.
UNASSIGNED: ClinicalTrials.gov registration NCT05868551 ( https://clinicaltrials.gov/study/NCT05868551).
UNASSIGNED: 1.1, dated 09/05/2023.

BACKGROUND: The World Health Organization has proposed that onchocerciasis elimination (interruption) of transmission be verified in 12 (approximately a third) endemic countries by 2030. The strategy to reach this goal is based on ivermectin Mass Drug Administration (MDA) with high geographical and therapeutic coverage. In addition to coverage, high levels of treatment adherence are paramount. We investigated factors associated with ivermectin intake in an area of Ghana with persistent Onchocerca volvulus infection.
METHODS: In August 2021, a cross-sectional mixed-methods study was conducted in 13 onchocerciasis-endemic communities in the Bono Region of Ghana. Individuals aged ≥ 10 years were invited to participate in a questionnaire survey. A total of 48 focus group discussions and in-depth interviews with 10 community drug distributors and 13 community leaders were conducted.
RESULTS: A total of 510 people participated in the study [median age: 32, interquartile range 30 (20‒50) years]; 274 (53.7%) were females. Of the total, 320 (62.7%) declared that they adhered to each treatment round and 190 (37.3%) admitted they had not taken ivermectin during at least one MDA round, since becoming eligible for treatment. Of 483 participants with complete information, 139 (28.8%) did not take ivermectin during the last round (March 2021), and 24 (5.0%) had never taken ivermectin (systematic non-adherers). Reasons for not taking ivermectin included previous experience/fear of side-effects, being absent during MDA, pregnancy, the desire to drink alcohol, and drug distribution challenges. Being male, having good knowledge and perception of the disease, and not having secondary or higher level of formal education were significantly associated with higher odds of ivermectin intake.
CONCLUSIONS: A relatively high level of non-adherence to ivermectin treatment was documented. There is a need for targeted educational and behavioural change campaigns to reverse these trends and ensure a steady course toward meeting onchocerciasis elimination targets in Ghana.