Onchocerciasis causes severe morbidity in sub-Saharan Africa. Abia, Anambra, Enugu, and Imo states of Nigeria were historically classified meso- or hyperendemic and eligible for ivermectin mass drug administration (MDA). After ≥25 years of annual and biannual MDA, serological and entomological assessments were conducted to determine if Onchocerca volvulus transmission was interrupted. Dried blood spots collected in October 2020 from ≥3167 children 5-9 years old in each state were screened for O. volvulus-specific Ov16 antibody by enzyme-linked immunosorbent assay. Additionally, 52,187 Simulium damnosum heads (≥8845 per state) collected over 12 months between 2021 and 2022 were tested by pooled polymerase chain reaction (PCR) for O-150 DNA. Among seven seropositive children, four were found for follow-up skin snip PCR to confirm active infection. Three were negative and the fourth was excluded as he was visiting from an endemic state. The final seroprevalence estimates of each state had 95% upper confidence limits (UCL) < 0.1%. All fly pools were negative by O-150 PCR, giving a 95% UCL infective fly prevalence < 0.05% in each state. Each state therefore met the World Health Organization epidemiological and entomological criteria for stopping MDA effective January 2023. With 18.9 million residents eligible for MDA, this marked the largest global onchocerciasis stop-treatment decision to date.

Blackfly members of the Simulium damnosum complex are major vectors of the parasite that causes onchocerciasis in Africa and Yemen, with other vector species involved in a few localized areas of Africa and in the Neotropics. Although the life cycle of these blackflies is linked to fast-flowing rivers, they can travel long distances (up to at least 500 km), calling into question how transmission zones are defined. Knowledge of the short- and long-range dispersal of these vectors could inform where control interventions and monitoring are necessary if targets for onchocerciasis elimination are to be met. Yet, research on blackfly dispersal has been limited and fragmented over the last 70 years. Here, we review the literature on the dispersal of onchocerciasis vectors, and we show the need for further research to establish how far larvae can travel downstream; the extent to which adults invade transmission zones; and whether adults migrate in a series of successive short movements or in single long-distance shifts, or use both methods.

Although lymphatic filariasis and onchocerciasis have been targeted for global elimination, these helminth infections are still a major public health problem across the tropics and subtropics. Despite decades of research, treatment options remain limited and drugs that completely clear the infections, and can be used on a large scale, are still unavailable. In the present review we discuss the strengths and weaknesses of currently available treatments and new ones in development. Novel candidates (corallopyronin A, DNDi-6166, emodepside, and oxfendazole) are currently moving through (pre)clinical development, while the development of two candidates (AWZ1066S and ABBV-4083/flubentylosin) was recently halted. The preclinical R&D pipeline for filarial infections continues to be limited, and recent setbacks highlight the importance of continuous drug discovery and testing.

Moxidectin is approved by the US Food and Drug Administration (US FDA) for the treatment of onchocerciasis (river-blindness) due to Onchocerca volvulus in patients aged 12 years and older. In onchocerciasis-endemic areas, mass drug administration (MDA) programs with ivermectin, with or without vector control, aim to control the disease, reduce morbidity, interrupt transmission, and more recently, achieve elimination. Moxidectin has the potential to be used in MDA programs. In countries where onchocerciasis is endemic, infants are often breastfed up to the age of 2 years, suggesting that some women are likely to be lactating during such periodic MDA programs. Quantitative analyses of non-clinical and clinical data using non-compartmental analysis and population based pharmacokinetic (popPK) modeling as well as physiologically based pharmacokinetic modeling (PBPK) were performed to determine the amount of moxidectin excreted in breast milk and subsequent exposures in the infant. The results of the analyses were similar. Concentrations of moxidectin in breast milk followed a similar pattern to those in plasma, with maximum concentrations occurring approximately 4 hours after dosing followed by a rapid decline in both breast milk and plasma. As early as two days after dosing, concentrations of moxidectin in breast milk were below the threshold for acceptable daily intake levels established by the European Medicines Agency (EMA) and FDA for secondary exposures from veterinary use, and below the WHO recommended relative infant dose (RID) safety threshold. The analyses were conducted to support prescribers and policy makers on dosing recommendations for moxidectin in lactation.

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Can the antibiotic doxycycline unlock new possibilities in the fight against onchocerciasis-associated epilepsy (OAE)? Idro et al. explored this question by investigating for the first time doxycycline\'s impact on nodding syndrome (NS), a severe manifestation of OAE. Results reveal significant findings that may shape future treatment strategies.

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.

Retrospective cohort studies in Cameroon found an association between Onchocerca volvulus microfilarial load in childhood (measured in 1991-1993) and risk of developing epilepsy later in life (measured in 2017). We parameterised and integrated this relationship (across children aged 3-15 years) into the previously published, stochastic transmission model, EPIONCHO-IBM, for Simulium damnosum sensu lato-transmitted onchocerciasis. We simulated 19 years (1998-2017) of annual ivermectin mass drug administration (MDA) reflecting coverage in the study area, and modelled epilepsy prevalence and incidence. Scenario-based simulations of 25 years of (annual and biannual) MDA in hyper- and holoendemic settings, with 65% and 80% therapeutic coverage, were also conducted. EPIONCHO-IBM predicted 7.6% epilepsy prevalence (compared to 8.2% in the Cameroon study) and incidence of 317 cases/100,000 person-years (compared to 350). In hyperendemic areas, 25 years of biannual MDA (80% coverage) eliminated onchocerciasis-associated epilepsy (OAE) and protected untreated under-fives from its development. Strengthening onchocerciasis programmes, implementing alternative strategies, and evaluating treatment for under-fives and school-age children are crucial to prevent OAE in highly-endemic settings.

BACKGROUND: The World Health Organization\'s 2021-2030 Road Map for Neglected Tropical Diseases boosted global commitment towards the elimination of onchocerciasis, but the timeline to elimination will vary strongly between countries in Africa. To assess progress towards elimination in the Republic of Togo, we reviewed the history of control and time trends in infection.
RESULTS: We collated all available programmatic, entomological, and epidemiological data since the initiation of the Onchocerciasis Control Programme (OCP) in Togo through different data sources. We then visualised data trends over time, to assess the impact of interventions on infection and transmission levels. Vector control was initiated by OCP from 1977 (northern and central parts of Togo) or 1988 (southern regions) up to 2002 (most areas) or 2007 (\"special intervention zones\" [SIZ], parts of Northern and Central Togo). Between 1988 and 1991, Togo initiated ivermectin mass drug administration (MDA) in eligible communities. The impact of vector control was high in most river basins, resulting in low annual biting rates and annual transmission potential declining to very low levels; the impact was lower in river basins designated as SIZ. Repeated, longitudinal ivermectin mass treatments have overall strongly reduced onchocerciasis transmission in Togo. Epidemiological surveys performed between 2014 and 2017 showed that the prevalence of skin microfilariae (mf) and anti-OV16 IgG4 antibodies had declined to low levels in several districts of the Centrale, Plateaux, and Maritime region. Yet, relatively high mf prevalences (between 5.0% and 32.7%) were still found in other districts during the same period, particularly along the Kéran, Mô and Ôti river basins (SIZ areas).
CONCLUSIONS: Trends in infection prevalence and intensity show that onchocerciasis levels have dropped greatly over time in most areas. This demonstrates the large impact of long-term and wide-scale interventions, and suggest that several districts of Togo are approaching elimination.

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.