Matthew A. Dixon

Background: The World Health Organization proposes that elimination of onchocerciasis transmission (EOT) be verified in 12 endemic countries by 2030. In sub-Saharan Africa (SSA), where most cases occur, Niger is the only country that has been verified to date. Despite decades of ivermectin mass drug administration (MDA), infection persists in West and Central Africa. Alternative treatment strategies (ATS) are necessary to accelerate progress towards EOT by 2030 and beyond. Methods: We used the EPIONCHO-IBM transmission model to project the number of years, from 2026, to reduce microfilarial (mf) prevalence below 1% across 1,634 implementation units (IUs) in 19 SSA countries. We fitted the model to geostatistically-derived mf prevalence in 1975, 2000 and 2018, and projected mf prevalence through to 2025. We classified IUs according to their baseline endemicity, intervention history programmatic performance, and current (2025) MDA frequency (annual or biannual). For those IUs that would not reach < 1% mf prevalence by 2030 if current strategies were continued, we simulated ATS (increasing treatment frequency, improving coverage, and adopting moxidectin MDA) from 2026 to 2040. Results: Of the 1,486 IUs currently under annual ivermectin MDA, 45% would require ATS. In those low-moderate endemicity IUs, biannual ivermectin would have a comparable impact to that of switching to annual moxidectin; in those with high endemicity, adopting biannual moxidectin would be more impactful. Of the 148 IUs currently receiving biannual ivermectin, 24% would benefit from ATS, switching to biannual moxidectin being the best option. Conclusion: This work brings into sharper focus which IU profiles are most likely to require ATS across SSA. In highly-endemic IUs with long intervention histories, biannual moxidectin MDA may be required under our modelling assumptions, with substantial uncertainty surrounding the permanent sterilising effect, of the two drugs under comparison, upon adult female worms. National programmes aiming to reach EOT will have options that need to be balanced against financial considerations. Implementation studies will also be important for translating these modelling projections into national policy decisions, particularly where different intervention strategies generate similar epidemiological benefits. Economic and epidemiological evaluations of repeated moxidectin MDA are needed to inform these decisions.

The World Health Organization aims to verify elimination of onchocerciasis transmission in 12 endemic countries by 2030. Serological assays detecting IgG4 antibodies against the Onchocerca volvulus Ov16 antigen guide decision-making regarding start- and stop-mass ivermectin treatment, post-treatment and post-elimination surveillance. Transmission models are crucial for understanding anti-Ov16 IgG4 seroprevalence dynamics. Uncertainty associated with the parasite stage(s) stimulating seroconversion and duration of antibody persistence has hitherto hindered progress. We use the individual-based stochastic transmission model, EPIONCHO-IBM, to test hypotheses regarding the timing of seroconversion and seroreversion. We fit the model to data from (treatment-naïve) Gabon and validate it using data from Togo (four decades of control). The best-fit hypothesis is that seroconversion is elicited by near-patent/patent infection. The duration of antibody persistence remains uncertain. Our findings support the use of mechanistic transmission models to refine serological thresholds for start- and stop-treatment, and aid interpretation of post-treatment and post-elimination surveillance serological signals.

Background: The World Health Organization proposes that elimination of onchocerciasis transmission (EOT) be verified in 12 endemic countries by 2030. In sub-Saharan Africa (SSA), where most cases occur, Niger is the only country that has been verified to date. Despite decades of ivermectin mass drug administration (MDA), infection persists in West and Central Africa. Alternative treatment strategies (ATS) are necessary to accelerate progress towards EOT by 2030 and beyond. Methods: We used the EPIONCHO-IBM transmission model to project the number of years, from 2026, to reduce microfilarial (mf) prevalence below 1% across 1,634 implementation units (IUs) in 19 SSA countries. We fitted the model to geostatistically-derived mf prevalence in 1975, 2000 and 2018, and projected mf prevalence through to 2025. We classified IUs according to their baseline endemicity, intervention history programmatic performance, and current (2025) MDA frequency (annual or biannual). For those IUs that would not reach < 1% mf prevalence by 2030 if current strategies were continued, we simulated ATS (increasing treatment frequency, improving coverage, and adopting moxidectin MDA) from 2026 to 2040. Results: Of the 1,486 IUs currently under annual ivermectin MDA, 45% would require ATS. In those low-moderate endemicity IUs, biannual ivermectin would have a comparable impact to that of switching to annual moxidectin; in those with high endemicity, adopting biannual moxidectin would be more impactful. Of the 148 IUs currently receiving biannual ivermectin, 24% would benefit from ATS, switching to biannual moxidectin being the best option. Conclusion: This work brings into sharper focus which IU profiles are most likely to require ATS across SSA. In highly-endemic IUs with long intervention histories, biannual moxidectin MDA may be required under our modelling assumptions, with substantial uncertainty surrounding the permanent sterilising effect, of the two drugs under comparison, upon adult female worms. National programmes aiming to reach EOT will have options that need to be balanced against financial considerations. Implementation studies will also be important for translating these modelling projections into national policy decisions, particularly where different intervention strategies generate similar epidemiological benefits. Economic and epidemiological evaluations of repeated moxidectin MDA are needed to inform these decisions.

Background: Taenia solium, colloquially called the pork tapeworm, is a zoonotic parasite with a human definitive host and a porcine intermediate host. Humans can become an aberrant intermediate host due to accidental ingestion of parasite eggs from the environment or through autoinfection, resulting in human cysticercosis (HCC), or neurocysticercosis (NCC) if the central nervous system is infected. Pigs become infected with the larval stage, porcine cysticercosis (PCC), through the ingestion of parasite eggs shed by humans through defecation. Malawi has been classified as endemic for T. solium by the WHO based on the presence of key risk factors; however, the subnational distribution is not known. To ensure the appropriate resources are mobilized to support targeted future T. solium control measures in Malawi, there is a need to understand the variation in T. solium endemicity status across the country. Methods: The current study uses a systematic literature review (SLR) using a pre-registered protocol; (PROSPERO CRD42023411044) to collate all available evidence on T. solium in Malawi. A geospatial risk mapping approach was conducted based on data from Malawi Demographic and Health Surveys (MDHS), and pig density data from the Food and Agriculture Organization (FAO) database to create geospatial risk maps of endemic subnational areas for 2000, 2004, 2010, and 2016. To create a single composite risk factor map for the four years from the MDHS, each parameter was plotted as a binary variable with the high or low risk categories and overlaid into a single composite risk factor classification. Additional data from hospital records on NCC and meat inspection records across several Agricultural Development Divisions (ADDs) were also collected. Results: A total of 9 studies were identified through the SLR, with 8 studies focused on HCC, including one study studying both HCC and PCC, and one study on PCC. The review of the hospital reports captured 38 reports of NCC, with the cases being from around the location of the two major hospitals. PCC rates in slaughter animals substantially varied among the six ADDs, with the highest rates being in Mzuzu ADD, with 3.7 cases per 100 ps-years ^-1 , and in Salima ADD, with 4.5 cases 100 ps-years ^-1 . Geospatial risk mapping results for the years 2000 to 2016 indicated that PCC risk factors exhibited substantial geographic and temporal variation. Areas at highest risk, with the presence of all three risk factors, were predominantly found in the central and southern districts of Malawi across years. High pig density and poverty in combination were evident across Malawi in 2000; however, these areas declined in northern districts between 2004 and 2016 while remaining consistent in central districts. The combined map from the four data streams did not provide validation for the risk maps but provided more robust evidence about the potential endemicity of the parasite in Malawi. Conclusions: Most studies identified from the SLR were case reports and mostly focused on HCC, with very limited literature available in terms of population-based studies. The confluence of high levels of poverty, poor sanitation, and high pig densities is evident in central and southern districts, indicating potential T. solium endemic areas warranting further investigation. Review of NCC cases from hospital records and PCC rates in slaughtered animals across ADDs further supports prioritizing these areas. Targeted epidemiological and socio-economic studies to inform interventions in the possibly hyperendemic areas are urgently required.

Background: Despite decades of control interventions in sub-Saharan Africa, morbidity associated with Onchocerca volvulus infection still exerts a substantial burden of disease, arising from cutaneous, ocular and neurological manifestations. Methods: We developed and integrated a morbidity sub-model into our previously published individual-based, stochastic transmission model, EPIONCHO-IBM, including both reversible (severe itch, reactive skin disease (RSD)), and irreversible (skin atrophy, depigmentation, hanging groin) cutaneous sequelae, and eye disease (blindness, visual impairment). We modelled the relationship between onchocerciasis skin disease (OSD) and infection prevalence using pre-intervention data from northern Nigeria, and between onchocerciasis ocular disease (OOD) and infection intensity using data from the Onchocerciasis Control Programme in West Africa. We simulated the impact of ivermectin mass drug administration (MDA) upon OSD and OOD using data from Cameroon, Central African Republic, Nigeria, Sudan and Uganda. Results: Modelled age-specific OSD and OOD prevalence at baseline align well with reported prevalence estimates across the simulated range of endemicity levels but underestimate irreversible OSD in older age groups. Under MDA, we capture trends in infection prevalence, severe itch and irreversible OSD but underestimate reductions in RSD and blindness prevalence. Conclusions: Integrating morbidity outcomes into transmission dynamics modelling will help improve estimates of onchocerciasis disease burden and inform the effectiveness and cost-effectiveness of current and alternative interventions.

In sub-Saharan Africa (SSA), onchocerciasis control has been implemented for many decades, beginning in 1974 under the Onchocerciasis Control Programme in West Africa (OCP) and in 1995 in Central and East Africa (plus Liberia) under the African Programme for Onchocerciasis Control (APOC). Since the establishment of the Expanded Special Project for Elimination of Neglected Tropical Diseases (ESPEN) in 2016, data on mass drug administration (MDA) with ivermectin has been centrally compiled for all endemic countries at implementation unit (IU) level, beginning in 2013. This paper presents HISTONCHO, a dataset collating detailed information on interventions, including vector control, from 1975 through to 2022, using the ESPEN portal (2013–2022), regional and country reports, implementation partners’ records, and published literature. Reconstructing such intervention histories is crucial for an understanding of their evolution, modelling their impact, and tailoring future interventions. We discuss strengths and limitations associated with the ESPEN database, and how HISTONCHO can be improved to support modelling of intervention strategies as well as onchocerciasis control and elimination efforts by endemic country programmes.

The World Health Organization aims to verify the elimination of onchocerciasis transmission in one-third of endemic countries by 2030, principally through mass drug administration (MDA) of ivermectin. Serological assays that detect IgG4 antibodies against the Onchocerca volvulus Ov16 antigen are central to decision-making regarding start- and stop-MDA, post-treatment surveillance and post-elimination surveillance. Transmission models have a crucial role to play in understanding anti-Ov16 IgG4 seroprevalence dynamics, but uncertainty associated with the parasite stage(s) that stimulate(s) seroconversion and the duration of antibody persistence have hitherto hindered progress. Using the individual-based stochastic transmission model, EPIONCHO-IBM, we tested several hypotheses on the timing of anti-Ov16 IgG4 seroconversion and seroreversion. We fitted the model to data from treatment-naïve communities in Gabon and validated its predictions using data collected in Togo after 39 years of onchocerciasis interventions. The model best reproduced observed patterns when anti-Ov16 IgG4 seroconversion was elicited by near-patent/patent infection, marked by the production of O. volvulus microfilariae by a mating worm pair. The duration of antibody persistence remains uncertain. These findings support the use of mechanistic transmission models to refine serological thresholds for initiating and safely stopping MDA, and to aid interpretation of serological signals in post-treatment and post-elimination surveillance.

Background Despite decades of control interventions in sub-Saharan Africa, morbidity associated with Onchocerca volvulus infection still exerts a substantial burden of disease, arising from cutaneous, ocular and neurological manifestations. Methods We developed and integrated a morbidity sub-model into our previously published individual-based, stochastic transmission model, EPIONCHO-IBM, including both reversible (severe itch, reactive skin disease (RSD)), and irreversible (atrophy, depigmentation, hanging groin) cutaneous sequelae, and eye disease (blindness, visual impairment). We modelled the relationship between onchocerciasis skin disease (OSD) and infection prevalence using pre-intervention data from northern Nigeria, and between onchocerciasis ocular disease (OOD) and infection intensity using data from the Onchocerciasis Control Programme in West Africa. We simulated the impact of ivermectin mass drug administration (MDA) upon OSD and OOD using data from Cameroon, Central African Republic, Nigeria, Sudan and Uganda. Results Modelled age-specific OSD and OOD prevalence at baseline aligned well with reported prevalence estimates across the simulated range of endemicity levels but underestimated irreversible OSD in older age groups. Under MDA, we captured trends in infection prevalence, severe itch and irreversible OSD but underestimated reductions in RSD and blindness prevalence. Conclusions Integrating morbidity outcomes into transmission dynamics modelling will help improve estimates of onchocerciasis disease burden and inform the effectiveness and cost-effectiveness of current and alternative interventions.

In sub-Saharan Africa (SSA), onchocerciasis control has been implemented for many decades, beginning in 1974 under the Onchocerciasis Control Programme in West Africa (OCP) and in 1995 in Central and East Africa (plus Liberia) under the African Programme for Onchocerciasis Control (APOC). Since the establishment of the Expanded Special Project for Elimination of Neglected Tropical Diseases (ESPEN) in 2016, data on mass drug administration (MDA) with ivermectin has been centrally compiled for all endemic countries at implementation unit (IU) level, beginning in 2013. This paper presents HISTONCHO, a database collating detailed information on interventions, including vector control, from 1975 through to 2022, using the ESPEN portal (2013-2022), regional and country reports, implementation partners’ records, and published literature. Reconstructing such intervention histories is crucial for an understanding of their evolution, modelling their impact, and tailoring future interventions. We discuss strengths and limitations associated with the ESPEN database, and how HISTONCHO can be improved to support modelling of intervention strategies as well as onchocerciasis control and elimination efforts by endemic country programmes.

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.