RARE DISEASE
Onchocerciasis
Onchocerciasis
Onchocerciasis
Drug discovery
4
drugs
With orphan designations
Overview
Onchocerciasis, caused by the filarial nematode Onchocerca volvulus, is transmitted through Simulium blackfly bites. It manifests as chronic pruritic dermatitis, subcutaneous nodules, and progressive vision loss, including irreversible blindness. Endemic in 31 sub-Saharan African countries and isolated South American foci, it affects rural populations near fast-flowing water sources. Management relies on mass ivermectin administration and adjunct doxycycline targeting Wolbachia endosymbionts [1][5][8].
Key Clinical Highlights
Therapies
Annual/biannual ivermectin MDA: Reduces microfilariae but requires 10–15 years of adherence [1][12][16].
Doxycycline (100 mg/day for 6 weeks): Sterilizes adult worms by targeting Wolbachia [5][8].
Vector control (larvicides) in high-transmission zones; emerging moxidectin trials show prolonged microfilaricidal suppression [2][16].
Categories: rare infectious diseases
Research Papers
1,273 drug discovery papers about Onchocerciasis, with 1 first-in-class and 10 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,273 drug discovery papers about Onchocerciasis, with 1 first-in-class and 10 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-09-17 | Diethylcarbamazine: A review of its modes of action.
Filariases are neglected tropical diseases caused by Clade III parasitic nematodes transmitted by biting insects as microfilaria which mature into female and male adults in the host. One example of filariasis is lymphatic filariasis or elephantiasis, caused by three species of filaria: Brugia malayi, Wuchereria bancrofti, and/or Brugia timori. Elephantiasis results from the occlusion of lymphatic vessels by adult parasites and subsequent swelling of the limbs. It is a disfiguring disease that occurs in 120 million people worldwide. Another filarial disease is onchocerciasis caused by Onchocerca volvulus. Microfilaria of this parasite invade the eye producing corneal scarring and blindness. The infected female blackflies that transmit these microfilaria belong to the Simulium genus, and breed in fast flowing rivers. Onchocerciasis occurs near these rivers and gives rise to the common name of the disease, i.e., "river blindness." Diethylcarbamazine (HetrazanR) was described as effective for treating filariases over 75 years ago by Yellapragada Subbarow and collaborators and is currently still in use. Diethylcarbamazine is characterized by a simple but flexible structure that provides it with the ability to combine with several target proteins, and a complex mode of action with effects on both filarial parasites and hosts. This Chapter reviews new observations on the activation of Transient Receptor Potential (TRP) ion-channels of B. malayi and older observations on the mechanisms of action of diethylcarbamazine. Diethylcarbamazine has three major effects: 1) A direct activating effect on filaria TRP channels producing transient inhibition of motility; 2) Reduction of host and parasite PGI2 and PGE2 production, thereby reducing host immune suppression; and 3) Activation and adhesion of host granulocytes which attack the filaria. We emphasize recent observations that include activation of TRP channels by diethylcarbamazine, an underappreciated mode of action of this classic anthelmintic.
2026-08-31 | Epidemiological and entomological assessment of persistent onchocerciasis transmission after long-term ivermectin treatment in communities along the Kéllé river, Cameroon
Despite two decades of annual Community-Directed Treatment with Ivermectin (CDTI) in the Eséka health district, onchocerciasis transmission persists in frontline villages along the Kéllé River. This study assessed the current epidemiological and entomological status to guide elimination strategies. We conducted cross-sectional clinical and parasitological surveys in two first-line villages (Pouth-Kéllé and Mapan) during June and July 2021. Skin snips were examined for Onchocerca volvulus microfilariae, and clinical manifestations were assessed. Monthly blackfly collections by human landing catches (HLC) were performed at four river sites over one year. Flies were dissected to detect O. volvulus larvae. Microfilarial prevalence was 18.7% (14/75) in Pouth-Kéllé and 15.6% (5/32) in Mapan. Palpable nodules were found in 10% and 6.3% of adults, respectively, reflecting chronic lesions despite recent ivermectin distribution. Reduced visual acuity was frequent (46.7% in Pouth-Kéllé, 47% in Mapan) and was significantly associated with microfilarial positivity in Pouth-Kéllé ( p = 0.04). Entomological surveys yielded a total of 9,163 blackflies collected across the four capture sites, of which 6,036 were dissected to detect O. volvulus larvae. Analysis of biting rates showed that collected point I (P1) exhibited the highest annual biting rate (40,500 bites/person/year), with marked seasonality peaking in April. Transmission risk persisted at collected point II (P2 –annual transmission potential: 14.3 infective larvae/person/year) and collected point IV (P4 − 10.0 infective larvae/person/year). Onchocerciasis transmission remains active in the Kéllé River basin despite two decades of ivermectin treatment. These findings support the urgent need for complementary and/or alternative strategies to achieve elimination of onchocerciasis.
2026-08-15 | Sustained Drug Exposure Drives Efficacy in Mice: PK/PD Analysis of Corallopyronin A against Wolbachia using Physiologically Based Absorption Modeling.
Corallopyronin A (CorA) depletes essential Wolbachia endosymbionts of filarial nematodes and is therefore a promising candidate for treating the neglected tropical diseases lymphatic filariasis and onchocerciasis. To optimize anti-Wolbachia therapy, the pharmacokinetic/pharmacodynamic (PK/PD) relationship was investigated. Due to the intra-nematode and -cellular target, conventional minimal inhibitory concentration could not be determined. Instead, an iterative approach was used to define PD efficacy thresholds and compare them with IC₅₀/IC₉₀ values from infected cells. A physiologically based biopharmaceutics model (PBBM) was developed in GastroPlus®, incorporating physicochemical in vitro and in vivo parameters to predict PK in mice. A mechanistic dissolution model for a CorA-povidone suspension was implemented and verified with in vivo single dose PK data. Simulations provided trough and peak concentrations (Cmax), AUC and time above threshold for multiple dosing regimens. In vivo efficacy was assessed in a Litomosoides sigmodontis mouse infection model by quantifying Wolbachia burden. CorA showed potent in vitro activity (IC₅₀/ IC₉₀: 0.007/0.030 µg/mL). In vivo, fractionated dosing improved efficacy. Cmax poorly predicted treatment outcome, while trough concentration and AUC over iterative model dependent efficacy threshold correlated strongly with the Wolbachia reduction (R²: 0.89 and 0.81). These thresholds show strong concordance with the experimentally determined IC₅₀/IC₉₀ values. The duration of drug exposure above 2.25 µg/mL was the most accurate predictor of efficacy (R²: 0.93). Based on the PK/PD modeling, an effective mouse dose of 16 mg/kg BID was identified. These findings highlight the importance of sustained drug exposure for optimizing CorA regimens and will guide clinical development.
2026-08-12 | Assessing the efficacy of high-dose rifampicin plus albendazole against onchocerciasis.
Onchocerciasis, also known as river blindness, remains a public health challenge in tropical regions. Despite significant gains through mass drug administration (MDA) with ivermectin, the infection remains persistent in many endemic foci. While the disease burden has reduced, elimination may require alternative strategies, including macrofilaricidal therapies. Rifampicin (RIF) has demonstrated strong anti-Wolbachia activity in vitro and in animal models, but its clinical efficacy in humans remains uncertain. We conducted a phase II randomized, controlled trial in Ghana to evaluate the safety and efficacy of high-dose RIF (35 mg/kg/day) combined with albendazole (ALB, 400 mg/day) as an alternative treatment for onchocerciasis. The study randomized 120 infected participants into one of four arms: RIF + ALB for 14 days (TA1), RIF + ALB for 7 days (TA2), ALB alone for 14 days (TA3), and a No Treatment control group (TA4). Treatment efficacy, including Wolbachia and microfilariae (MF) depletion, adult worm vitality and embryogenesis were assessed following treatment at 4-, 18-, and 20-months. High-dose RIF + ALB was safe and well-tolerated, associated with only mild, transient adverse events. Treatment with RIF + ALB for 14 days reduced Wolbachia load in skin MF at 4 months (47.9%; p = 0.018). ALB monotherapy showed sustained reductions in skin microfilarial densities at the 18- and 20-month time points (p < 0.05). However, no macrofilaricidal effect or sustained Wolbachia depletion in adult worms was observed in any group. High-dose RIF + ALB is safe with limited macrofilaricidal efficacy in clinical settings, contrasting with the superiority observed from preclinical trials. ALB alone shows promise as an alternative microfilaricidal treatment to ivermectin or as a complementary regimen. The lack of sustained efficacy of RIF as an anti-Wolbachia regimen may reflect suboptimal dosing, highlighting the need for further optimization of RIF-based regimens for onchocerciasis treatment. PACTR202009704006025 (https://pactr.samrc.ac.za/Search.aspx). Date of trial registration: September 9, 2020.
2026-08-01 | Modelling the impact of mass drug administration with ivermectin or moxidectin on human onchocerciasis when there is sub-optimal response of parasites to treatment.
Onchocerciasis is a disease caused by the filarial nematode parasite Onchocerca volvulus and is transmitted by blackflies after they ingest larval offspring, microfilariae, found in the skin of infected people. The elimination of transmission within endemic communities in sub-Saharan Africa, the Americas, and Yemen depends on mass drug administration of ivermectin (MDAi) at high treatment coverage until the prevalence of the parasite in people or in blackflies reaches below a threshold value. In Africa, there are a number of communities where worms that are less susceptible to the effects of ivermectin, i.e., that are sub-optimally responding (SOR), appear to be contributing to the persistence of onchocerciasis despite high-coverage MDAi. We have incorporated this variation in an epidemiological model to explore how the presence of SOR worms impacts the prevalence of people with skin microfilariae, fitting the model to epidemiological data from a community in Ghana, Asubende, where SOR has been detected. Incorporating a cumulative effect of ivermectin into the model fits the data better than if no cumulative effect is assumed. Simulations indicate that elimination is possible under biannual MDAi even if SOR worms are present in the starting population unless the baseline prevalence is hyperendemic. In a hyperendemic region, elimination is predicted if there is no SOR, but when SOR worms are included in the model, elimination is not reached even after twenty years of biannual MDAi with a treatment coverage of 80%. Biannual MDAi increases the proportion of reproducing female worms that would be characterized as SOR compared to annual MDAi. However, when using mass drug administration with moxidectin (MDAm), elimination becomes possible with fewer rounds of MDA even if there are worms that suboptimally respond to moxidectin. Our results support concerns raised in the research community that SOR to ivermectin in O. volvulus could result in persistent transmission despite high-coverage, biannual MDAi, but that MDAm could pose a solution, should safety and efficacy trials support its distribution.
vaccines
2026-07-01 | Safety and immunogenicity of an adjuvanted human onchocerciasis vaccine candidate, OvMANE1: preclinical evaluation in a mice model.
Onchocerciasis, caused by the filarial worm Onchocerca volvulus, remains a major public health challenge because of the limitations of ivermectin-based control strategies, thereby highlighting the need for more innovative tools such as vaccines. This study investigated the safety and immunogenicity of a novel multi-epitope chimeric antigen, OvMANE1 formulated with Freund's adjuvant, in BALB/c mice. Mice were immunised at three time points of 2-week intervals, with blood collected at each point to measure antibody levels and immune cells. Adjuvanted-OvMANE1 exhibited a promising safety profile, revealing neither any physical signs of toxicity nor behavioural abnormalities. Immunological assays showed significant increases in total IgG absorbance (OD 450 nm) after the first (P = 0.0260) and final booster doses (P = 0.026). Total IgG (P = 0.0086) and IgG1 (P = 0.0465) absorbances also increased significantly over the study period, suggesting sustained humoral immunity. Moreover, cellular responses were significantly enhanced, with elevated leucocyte count (P = 0.0190) and increased lymphocyte activity (P = 0.0397) observed in the adjuvanted-OvMANE1 group compared to the control. Indeed, total leucocytes increased progressively from Day 0 to Day 39, with significant differences recorded in the test group between doses: Days 0-14 (P = 0.0043) and Days 14-28 (P = 0.0079). The pronounced production of relevant antibodies and induction of cellular immunity is indicative of a mixed Th1/Th2 response and antibody-dependent cellular cytotoxicity (ADCC) targeting O. volvulus L3 and/or other larval stages of the parasite. These results position OvMANE1 as a promising vaccine candidate against human onchocerciasis. However, further in vivo studies are needed to confirm and expand these findings.
2026-03-30 | Onchocerciasis overview: pathogenesis, clinical spectrum, and therapeutic challenges of a neglected tropical disease.
Onchocerciasis is still a major health burden in sub-Saharan Africa and Yemen, where many cases occur as control efforts face persistent obstacles, while smaller, well-defined transmission foci remain in Brazil and Venezuela. Caused by the filarial nematode Onchocerca volvulus and transmitted by blackflies, the disease causes progressive disability, economic loss, and hampers community development. Despite decades of mass drug administration with ivermectin, the inability of the drug to kill adult worms, increasing concerns over resistance, and the lack of effective vaccines continue to hinder elimination strategies. This review provides an overview of the disease, discussing its transmission dynamics, pathogenesis, clinical manifestations, diagnosis, and treatment. It also examines the immune-mediated responses that drive tissue damage and chronic morbidity, with an emphasis on skin and ocular complications. We highlight the need for rapid, non-invasive, and cost-effective diagnostic tools to enhance disease surveillance and assessment of treatment. Finally, we discuss the limitations of current therapies and recent progress in vaccine development, particularly subunit and multi-epitope vaccine candidates identified through reverse vaccinology approaches. Together, these insights reinforce the need for integrated strategies, combining improved diagnostics, novel treatments, and vaccines, to drive progress toward onchocerciasis elimination.
2025-10-23 | Vaccination against Onchocerca volvulus induces IgG-mediated protective immunity dependent on neutrophils and complement.
Onchocerciasis remains a significant cause of morbidity and economic loss in sub-Saharan Africa. Despite the existence of effective therapeutics, a prophylactic vaccine targeting the etiologic agent, Onchocerca volvulus, is needed to control ongoing disease and transmission. Mice were vaccinated against O. volvulus with a fusion of the recombinant antigens Ov-103 and Ov-RAL-2 (Ov-FUS-1) with Advax-CpG adjuvant. Immunized mice developed protective immunity with the killing of third-stage larvae (L3) within 36 h of challenge infection. IgG from immunized mice passively transferred protective immunity to naïve mice, indicating that antigen-specific IgG mediated parasite elimination. Neutrophils were the most abundant subset of immune cells recruited to the parasite microenvironment in vivo, and treating mice with a granulocyte-depleting antibody resulted in the total loss of immune-mediated larval killing. Analysis of neutrophil gene expression revealed that both vaccination and the presence of O. volvulus larvae were capable of modulating neutrophil transcriptional activity. The mechanism by which antigen-specific IgG and neutrophils collaborated to kill L3 was independent of Fcγ receptors. However, the elimination of complement component C3 prevented vaccine-induced protection, which suggests these components may interact through the complement system. This study describes a vaccine-induced mechanism of protective immunity against O. volvulus L3 dependent on IgG, neutrophils, and complement, highlighting an effective collaboration between the innate and adaptive arms of the immune system to control O. volvulus infection.
2025-05-02 | Safety and immunogenicity of an adjuvanted human onchocerciasis vaccine candidate, Ov MANE1: preclinical evaluation in mice model
Abstract Onchocerciasis, caused by the filarial worm Onchocerca volvulus, remains a major public health challenge due to the limitations of ivermectin-based control strategies, thereby, highlighting the need for more innovative tools like vaccines. This study investigated the safety and immunogenicity of a novel multi-epitope chimeric antigen, OvMANE1 formulated with Freund’s adjuvant, in BALB/c mice. Following mice immunization at three time points of 2-week intervals, adjuvanted-OvMANE1 exhibited a promising safety profile, revealing neither any physical signs of toxicity nor behavioural abnormalities. Immunological assays showed significant increases in total IgG levels after the first (p = 0.0260) and final booster doses (p = 0.026). Interestingly, total IgG (p = 0.0086) and IgG1 (p = 0.0465) levels also increased significantly over the study period highlighting the ability of OvMANE1 to sustain humoral immunity. Moreover, cellular responses were significantly enhanced, with elevated leukocyte count (p = 0.0190) and increased lymphocyte activity (p = 0.0397) observed in the adjuvanted-OvMANE1 group compared to the control. Indeed, total leukocytes increased progressively from day 0 to day 39, with significant differences recorded in the test group between doses: day 0 vs. day 14 (p = 0.0043) and day 14 vs. day 28 (p = 0.0079). The pronounced production of relevant antibodies and induction of cellular immunity strongly suggests that the antigen can elicit mixed Th1/Th2 responses and antibody-dependent cellular cytotoxicity (ADCC) targeting O. volvulus L3 and/or other larval stages of the parasite. These results clearly show the emergence of OvMANE1 as a promising vaccine candidate against human onchocerciasis. However, further studies to evaluate the antigens protective potential in other animal species are required.
2024-05-09 | Predictive Immunoinformatics Reveal Promising Safety and Anti-Onchocerciasis Protective Immune Response Profiles to Vaccine Candidates (Ov-RAL-2 and Ov-103) in Anticipation of Phase I Clinical Trials
Abstract Onchocerciasis is a devastating tropical disease that causes severe eye and skin lesions. As global efforts shift from disease control to elimination, prophylactic/therapeutic vaccines have emerged as alternative elimination tools. Notably, Ov -RAL-2 and Ov -103 antigens have shown great promise in preclinical studies and plans are underway for clinical trials. Here, we predict the immunogenicity and other vaccine-related parameters for both antigens using immunoinformatics, as potential vaccine candidates against onchocerciasis. The analysis reveals that both antigens exhibit a favourable safety profile, making them promising candidates poised for human trials. Importantly, in silico immune simulation forecasts heightened antibody production and sustained cellular responses for both vaccine candidates. Indeed, the antigens were predicted to harbour substantial numbers of a wide range of distinct epitopes associated with protective responses against onchocerciasis, as well as the potential for stimulating innate immune TLR-4 receptor recognition with Ov -103 exhibiting better structural efficiency and antigenicity with no homology to human proteins compared to Ov -RAL-2. Overall, we provide herein valuable insights for advancing the development of Ov -103 and RAL-2 vaccine candidates against onchocerciasis in humans. Author’s summary To address the significant impact of onchocerciasis, a tropical disease commonly known as river blindness, we have employed computational tools to assess the viability of two promising vaccine candidates, namely Ov -RAL-2 and Ov -103. Existing control strategies alone are insufficient to eliminate the disease. Our study utilises advanced immunoinformatics techniques to systematically evaluate the safety, antigenicity, and immunogenic properties of these antigens as potential vaccine candidates against onchocerciasis prior to human trials. Our analysis revealed that both vaccine candidates demonstrate favourable safety profiles and possess the capability to induce robust antibody responses and cellular immunity. Notably, we identified numerous distinct epitopes present within each vaccine candidate that are associated with protective immunity against onchocerciasis. The abundance of these epitopes suggests that both vaccine candidates have the potential to activate the immune system through diverse humoral and cellular response mechanisms. By providing these valuable insights, our research assists in guiding the development of Ov -103 and Ov -RAL-2 as effective vaccines against onchocerciasis. Ultimately, our findings contribute to the global endeavour to eliminate this debilitating disease and enhance the quality of life for the millions of affected individuals.
proteins
2022-04-01 | Development of a recombinant vaccine against human onchocerciasis.
Human onchocerciasis caused by the filarial nematode parasite Onchocerca volvulus remains a major cause of debilitating disease infecting millions primarily in Sub-Saharan Africa. The development of a prophylactic vaccine, along with mass drug administration, would facilitate meeting the goal of onchocerciasis elimination by 2030. Models used to study immunity to Onchocerca include natural infection of cattle with Onchocerca ochengi and O. volvulus infective third-stage larvae implanted within diffusion chambers in mice. A vaccine, comprised of two adjuvanted recombinant antigens, induced protective immunity in genetically diverse mice suggesting that it will function similarly in diverse human populations. These antigens were recognized by immune humans and also induced protective immunity against Brugia malayi. We describe the development of a fusion protein composed of the two vaccine antigens with the plan to test the vaccine in cows and non-human primates as a prelude to the initiation of phase 1 clinical trials. The adjuvanted O. volvulus vaccine composed of two antigens Ov-103 and Ov-RAL-2 was shown to be consistently effective at inducing protective immunity using multiple immune mechanisms. The vaccine is ready for further evaluation in other animal models before moving to clinical trials in humans.
2018-05-01 | Onchocerca - infected cattle produce strong antibody responses to excretory-secretory proteins released from adult male Onchocerca ochengi worms
The front line molecules from filarial worms and other nematodes or helminthes are their Excretory-Secretory (ES) products. Their interaction with the host cells, proteins and immune system accounts for the skin and eye pathology or hyposensitivity observed in human onchocerciasis. ES products and adult worms’ crude extracts from Onchocerca ochengi, a filarial nematode that infects the African zebu cattle, were utilized in the present study as a model for studying Onchocerca volvulus that causes river blindness in man. The ES products were generated from adult male and female worms in vitro and analyzed with poly acrylamide gel electrophoresis (PAGE) and enzyme-linked immunosorbent assay (ELISA) using sera from Onchocerca-infected cattle and humans. The cattle sera were collected from a herd that had been exposed for six years to natural transmission of Onchocerca spp. The expressed reactivity was evaluated and differences analyzed statistically using Kruskal-Wallis rank and Chi-square tests. The gel electrophoretic analyses of 156 ES products from O. ochengi female and male worms and of two somatic extracts from three females and 25 males revealed differences in the protein pattern showing pronounced bands at 15, 30–50 and 75 kDa for male ES proteins and 15, 25 and 40–75 kDa for somatic extracts, respectively and less than 100 kDa for female worms. Proteins in the ES products and somatic extracts from female and male Onchocerca ochengi worms were recognized by IgG in sera from both Onchocerca-exposed cattle and humans. Bovine serum antibodies reacted more strongly with proteins in the somatic extracts than with those in the ES products. Interestingly, the reaction was higher with male ES products than with ES products from female worms, suggesting that the males which migrate from one nodule to another are more exposed to the host immune system than the females which remain encapsulated in intradermal nodules. This study demonstrates that O. ochengi ES products and, in particular, extracts from male filariae may represent a good source of immunogenic proteins and potential vaccine candidates.
2016-07-07 | The Immunomodulatory Role of Adjuvants in Vaccines Formulated with the Recombinant Antigens Ov-103 and Ov-RAL-2 against Onchocerca volvulus in Mice
Background In some regions in Africa, elimination of onchocerciasis may be possible with mass drug administration, although there is concern based on several factors that onchocerciasis cannot be eliminated solely through this approach. A vaccine against Onchocerca volvulus would provide a critical tool for the ultimate elimination of this infection. Previous studies have demonstrated that immunization of mice with Ov-103 and Ov-RAL-2, when formulated with alum, induced protective immunity. It was hypothesized that the levels of protective immunity induced with the two recombinant antigens formulated with alum would be improved by formulation with other adjuvants known to enhance different types of antigen-specific immune responses. Methodology/ Principal Findings Immunizing mice with Ov-103 and Ov-RAL-2 in conjunction with alum, Advax 2 and MF59 induced significant levels of larval killing and host protection. The immune response was biased towards Th2 with all three of the adjuvants, with IgG1 the dominant antibody. Improved larval killing and host protection was observed in mice immunized with co-administered Ov-103 and Ov-RAL-2 in conjunction with each of the three adjuvants as compared to single immunizations. Antigen–specific antibody titers were significantly increased in mice immunized concurrently with the two antigens. Based on chemokine levels, it appears that neutrophils and eosinophils participate in the protective immune response induced by Ov-103, and macrophages and neutrophils participate in immunity induced by Ov-RAL-2. Conclusions/Significance The mechanism of protective immunity induced by Ov-103 and Ov-RAL-2, with the adjuvants alum, Advax 2 and MF59, appears to be multifactorial with roles for cytokines, chemokines, antibody and specific effector cells. The vaccines developed in this study have the potential of reducing the morbidity associated with onchocerciasis in humans.
2015-09-14 | A Proteomic Analysis of the Body Wall, Digestive Tract, and Reproductive Tract of Brugia malayi
Filarial worms are parasitic nematodes that cause devastating diseases such as lymphatic filariasis (LF) and onchocerciasis. Filariae are nematodes with complex anatomy including fully developed digestive tracts and reproductive organs. To better understand the basic biology of filarial parasites and to provide insights into drug targets and vaccine design, we conducted a proteomic analysis of different anatomic fractions of Brugia malayi, a causative agent of LF. Approximately 500 adult female B. malayi worms were dissected, and three anatomical fractions (body wall, digestive tract, and reproductive tract) were obtained. Proteins from each anatomical fraction were extracted, desalted, trypsinized, and analyzed by microcapillary reverse-phase liquid chromatography-tandem-mass spectrometry. In total, we identified 4,785 B. malayi proteins. While 1,894 were identified in all three anatomic fractions, 396 were positively identified only within the digestive tract, 114 only within the body wall, and 1,011 only within the reproductive tract. Gene set enrichment analysis revealed a bias for transporters to be present within the digestive tract, suggesting that the intestine of adult filariae is functional and important for nutrient uptake or waste removal. As expected, the body wall exhibited increased frequencies of cytoskeletal proteins, and the reproductive tract had increased frequencies of proteins involved in nuclear regulation and transcription. In assessing for possible vaccine candidates, we focused on proteins sequestered within the digestive tract, as these could possibly represent "hidden antigens" with low risk of prior allergic sensitization. We identified 106 proteins that are enriched in the digestive tract and are predicted to localize to the surface of cells in the the digestive tract. It is possible that some of these proteins are on the luminal surface and may be accessible by antibodies ingested by the worm. A subset of 27 of these proteins appear especially promising vaccine candidates as they contain significant non-cytoplasmic domains, only 1–2 transmembrane domains, and a high degree of homology to W. bancrofti and/or O. volvulus.
2015-09-11 | Immune recognition of excretory and secretory products of the filarial nematode Onchocerca ochengi in cattle and human sera.
Excretory-secretory (ES) products of nematodes and other helminths are the first molecules to interact with cell surfaces and soluble proteins within the host. In the present study, ES products of the filarial nematode Onchocerca ochengi were investigated as a model for Onchocerca volvulus, the causative agent of river blindness. These products were collected from adult and larval stages in vitro over a period of 7 days, to compare their immunological recognition in cattle and human sera, infected with species of Onchocerca. From the 156 sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) ES products or extracts, protein bands showed different patterns between female and male products. A comparison of antibody recognition of the different ES products by sera from infected cattle and humans, when analysed by enzyme-linked immunosorbent assay (ELISA), revealed a relatively higher reactivity of the female somatic extract to human and cattle sera compared to ES products of both genders. Nevertheless, similar reactivity of the O. ochengi male and female ES products to human and cattle sera was noticed. As a result, the interaction of ES products with the surface of the host and immune system often led to host responses, including the generation of antibodies. The O. ochengi ES products are therefore good sources of potential immunogenic proteins. The identification of these ES products is in progress, with the aim of developing vaccine candidates against human onchocerciasis.
gene therapies
2026-09-06 | Spatial and seasonal dynamics of Simulium damnosum s.l. and entomological indicators of onchocercosis in the provinces of Huambo and Cuanza-Sul in Angola.
Onchocerciasis remains a public health problem in Angola. Despite the implementation of onchocerciasis control programs based on mass treatment with ivermectin, current entomological data remain limited, making it difficult to accurately assess the potential risk of transmission. Our objectives were to analyze the spatial and seasonal dynamics of Simulium damnosum s.l. and the main entomological indicators of onchocerciasis in the provinces of Huambo and Cuanza Sul, Angola, to assess the potential entomological risk of transmission. We captured black flies using the human bait capture method for 48 days between July and October 2025. Analyses of entomological indicators included abundance, monthly bite rate (MBR), parity, seasonality, daily activity, and monthly transmission potential (MTP). Morphological identification of specimens was performed according to standard taxonomic keys. A total of 6.038 black flies were captured during the study period, including 3.615 in Huambo and 2.423 in Cuanza Sul. All black flies belonged to species of the savanna group. The average BMR was high (1.890 bites/person/month), with significant seasonal variations. The overall parity rate reached 59%, significantly higher in Cuanza Sul. No black flies infected with Onchocerca volvulus were found, resulting in a zero PMT at all study sites. Despite high vector density and relatively old black fly populations, the absence of transmission suggests a reduction in onchocerciasis transmission in the studied regions. These results demonstrate the importance of maintaining regular entomological surveillance to prevent potential transmission in an ecological context favorable to the vector.
2026-03-29 | Programmatic implications of the efficiency of uptake of Onchocerca volvulus microfilaria by Simulium sp. vectors.
The current global aim for onchocerciasis is to eliminate transmission of infection by administering ivermectin once or biannually. However, when ivermectin treatment is given annually for 9-10 years, some individuals still carry low mf levels, which may allow continued transmission. 1608 newly emerged Simulium sanctipauli (Pra form) flies were fed on 35 volunteers at four different times (0, 8, 90, 365 days) after treatment with ivermectin, with initial dermal microfilarial loads ranging from 0 to >30 Onchocerca volvulus mf/mg skin. Ten days after feeding, the number and load of mf in these flies were assessed by dissection. Notably, even at the lowest skin snip mf densities-including those showing zero infection flies can still ingest O. volvulus microfilariae and become infected; 29% of the 1608 fed flies picked up microfilariae. The lowest skin mf levels were recorded on Day 90 after treatment, at which time vector mf uptake increased by 21% with every unit increase in skin mf density (p<0.000). Very low dermal mf levels can still support parasite transmission. Consequently, widespread low O. volvulus infection in human populations with highly productive vector-breeding sites could significantly affect efforts to eliminate transmission.
2026-02-27 | Integrated serosurveillance to assess disease elimination in coastal Ecuador: onchocerciasis, yaws, and trachoma.
Testing blood samples with multiplex bead assays can assess elimination and identify residual foci of transmission for multiple pathogens simultaneously. In Ecuador, onchocerciasis and yaws are presumed eliminated, and the status of trachoma is unknown. We assessed their elimination status by measuring IgG antibodies in children 6-24 months. In a birth cohort of 404 children measured between 2021-2024 in Esmeraldas province, Ecuador, we tested dried blood spots at ages 6, 9, 12, 18, and 24 months using a multiplex IgG assay that included antigens to Onchocerca volvulus (Ov16), Treponema pallidum (rp17, tmpa), and Chlamydia trachomatis (Pgp3, Ct694). We estimated seroprevalence and incident seroconversion rates across an urban-rural gradient. Of 404 children enrolled, 370 contributed 1,606 samples. Seroprevalence was near zero for onchocerciasis (0.4%, 95% CI: 0.2% to 0.8%) and yaws (0.2%, 95% CI: 0.0% to 0.5%). Conversely, C. trachomatis Pgp3 seroprevalence increased along the urban-rural gradient from Esmeraldas city (3.4%, 95% CI: 1.8% to 5.8%) to remote, river-accessible rural villages (22.4%, 95% CI: 16.0% to 30.1%), and incident seroconversion was common in rural villages (16.1 per 100 child-years, 95% CI: 11.3 to 21.9). Serologic surveillance found no evidence of O. volvulus or T. pallidum transmission, consistent with elimination. High Pgp3 seroconversion rates suggest ongoing C. trachomatis transmission in rural villages. Results highlight the value of integrated serologic surveillance and motivate in-depth trachoma surveillance in Esmeraldas.
2026-02-26 | Exploring potential pathogenesis mechanisms of onchocerciasis-associated epilepsy through cerebrospinal fluid analysis of children with complex febrile seizures: a pilot study in Aketi, Democratic Republic of the Congo.
Onchocerciasis, commonly known as river blindness, is a parasitic disease caused by Onchocerca volvulus affecting millions predominantly in sub-Saharan Africa. Robust epidemiological evidence points to a clinical relationship between onchocerciasis and epilepsy, a condition termed onchocerciasis-associated epilepsy (OAE). Despite extensive research and various successful elimination programmes over the past decades, the pathogenesis of OAE is still unknown. Current hypotheses propose that O. volvulus microfilaria, their excretory-secretory products or the newly discovered filarial O. volvulus RNA virus 1 (OVRV1) virus may traverse the blood-brain barrier, triggering seizures or immune responses that result in neurological damage. However, direct evidence of microfilaria or their DNA in cerebrospinal fluid (CSF) or brain tissue remains elusive, likely due to immune-mediated parasite clearance. Additionally, investigations into the potential neurotoxicity of these novel filarial viruses have yet to be pioneered. This prospective cohort study will involve 100 ivermectin-naïve children aged 2-5 years, recruited from rural communities in the Aketi health zone, located in the Democratic Republic of Congo. This region is known to be an onchocerciasis-endemic area with a high prevalence and transmission of OAE, despite years of community-directed treatment with ivermectin. Lumbar punctures (LP) will be performed in children presenting with complex febrile seizures according to WHO's paediatric guidelines. CSF samples will be examined for white blood cells, protein levels, glycorrhachia, microfilaria, OVRV1 and O. volvulus biomarkers. Children will be followed annually, monitoring the development of epilepsy and O. volvulus infection. This approach aims to elucidate the presence of O. volvulus and OVRV1 in the brain and their role in the pathogenesis of epileptic seizures and the myriad of clinical symptoms observed in OAE. The protocol has been approved by the Ethics Committee of the University of Kisangani (UNIKIS/CE/KGB/001/2025) and the University of Antwerp (project ID 7323-Edge n/a-BUN B3002025000078). Written informed consent will be obtained from all parents and/or legal guardians of children for whom an LP is considered. Findings will be disseminated at national and international levels via meetings and peer-reviewed open-source publications. Study data will be stored in an open repository. Pan African Clinical Trials Registry (PACTR202507670131109).
2025-08-08 | Physiological and Behavioral Effects of Onchocerca ochengi Infection in Gerbils: Implications for Onchocerciasis-Associated Epilepsy Research.
PURPOSE: This study aimed to investigate whether Onchocerca ochengi infection directly causes epilepsy. Although O. ochengi—a cattle parasite phylogenetically related to O. volvulus—shares biological similarities with its human counterpart, it has not been epidemiologically linked to epilepsy in bovines, unlike O. volvulus, which has been associated with onchocerciasis-associated epilepsy in humans. No prior experimental studies have established a causal relationship between onchocerciasis and epilepsy. METHODS: Gerbils were surgically implanted with O. ochengi worm masses (test group) or underwent sham operations (control group) to assess the infection’s effects. Survival rates were monitored post-implantation, and behavioral assessments were conducted on days 15–19 using the elevated plus maze, open-field, object recognition, and hanging wire tests. On day 21, the gerbils were sacrificed, and their body and organ weights were recorded, along with an analysis of worm mass survival. RESULTS: Implantation of 15 worm masses resulted in 100% mortality in the test group. When 10 worm masses were implanted, 53.3% of gerbils died, while all control gerbils survived. By day 21, an average of 1.4 out of 10 implanted worm masses remained viable, with a viability score of 93.3%. Test gerbils exhibited significant reductions in overall body weight and increased spleen weight compared to controls. However, behavioral tests revealed no significant differences between the two groups. CONCLUSION: While O. ochengi worm masses caused notable physical effects, including increased mortality and altered body and organ weights, no conclusive evidence was found linking the infection to behavioral changes indicative of epilepsy. Further research is necessary to explore the potential association between onchocerciasis and epilepsy development.
other
2022-10-17 | NKp46+ natural killer cells develop an activated/memory-like phenotype and contribute to innate immunity against experimental filarial infection.
Lymphatic filariasis and onchocerciasis are major neglected tropical diseases affecting over 90 million people worldwide with painful and profoundly disfiguring pathologies (such as lymphoedema or blindness). Type 2 inflammation is a hallmark of filarial nematode tissue infection and is implicated both in eosinophil dependent immunity and lymphatic or ocular immunopathologies. Type-2 innate lymphoid cells (ILC2) are known to play an important role in the initiation of type 2 inflammation in helminth infection. We therefore tracked comparative IL-12Rβ2+ ILC1, ST2+ ILC2 and NKp46+ natural killer (NK) innate lymphoid cell population expansions during Brugia malayi experimental peritoneal filarial infections using either immunocompetent or immunodeficient mice. In immunocompetent BALB/c animals, NKp46+ NK cells rapidly expanded representing over 90% of the ILC population in the first week of infection, whereas, surprisingly, ST2+ ILC2 failed to expand. NKp46+ NK cell expansions were confirmed in RAG2 deficient mice lacking adaptive immunity. Ablation of the NKp46+ NK cell compartment in RAG2 common gamma chain (gc) mice led to increased susceptibility to chronic adult B. malayi infection. This data was recapitulated using an Onchocerca ochengi male worm peritoneal implant model. When NKp46+ NK cells were depleted in RAG2 deficient mice using anti-NKp46 or asialo GM1 antibody injections over the first five weeks of B. malayi infection, susceptibility to adult B. malayi infection was significantly increased by 2-3 fold with concomitant impairment in eosinophil or neutrophil recruitments. Finally, we demonstrate that in RAG2 deficient mice, drug clearance of a primary adult B. malayi infection followed by challenge infection leads to resistance against early larval B. malayi establishment. This innate resistance is associated with bolstered NK and eosinophils whereby NKp46+ NK cells express markers of memory-like/enhanced activation (increased expression of interferon gamma and Ly6C). Our data promotes a novel functional role for NKp46+ NK cells in immunoprotection against experimental primary and secondary filarial infection which can proceed in the absence of adaptive immune regulation.
1997-05-01 | Production of both IFN-gamma and IL-5 by Onchocerca volvulus S1 antigen- specific CD4+ T cells from putatively immune individuals
Protective immunity to the parasitic nematode Onchocerca volvulus (Ov) appears to be directed against molecules of invading L3 larvae. In this study, the cellular immune reaction to such an Ov L3 protein (S1) which is protective in an animal model was analyzed using peripheral blood mononuclear cells (PBMC) of individuals from a hyperendemic area in West Africa who were exposed to Ov but remained free from disease ('putatively immune individuals'). Despite seronegativity of these individuals against S1, proliferation of PBMC was inducible, allowing generation of an S1-specific T cell line which produced IFN-gamma upon stimulation with both Ov lysate and S1. However, S1 induced significantly more IL-5 than Ov lysate. S1-specific, DQ6 (DQA1*0103/DQB1*0603)-restricted T cell clones were generated which reacted against synthetic peptides comprising amino acids 99-111 of S1. These clones, which are the first generated against a recombinant fllarial antigen, produced both IFN-gamma and IL-5 as well as little IL-4, suggestive of a Th0-like phenotype. In conclusion, in putative immunity, reactivity against a particular parasite protein can be detectable on the level of T but not B cells. Induction of both IFN-gamma and IL-5 by S1 suggests that it may trigger macrophage plus eosinophil dependent killing of L3 in vivo. The identification of a likely DQ6 (DQA1*0103/DQB1*0603)-restricted T cell epitope may be of more general relevance, given that allele combinations of DQ6, including DQA1*0103/DQB1*0603, are negatively associated with diabetes mellitus.
1994-03-01 | Cattle, worms and zooprophylaxis
Epidemiological studies in North Cameroon indicate that a high population density of cattle in relation to man protects from severe onchocerciasis. In the following, we present a mathematical model which allows to study the effects of zoophily of the vectors, of concomitant immunity in the human population and of cross-protective immunity caused by the infective larvae of a bovine parasite, Onchocerca ochengi, inoculated into man by Simulium damnosum s.l. Besides this influence on onchocerciasis, cattle also play a major role in the epidemiology of malaria (zooprophylaxis through vector dilution) and schistosomiasis (protection by crossreactive concomitant immunity).
1991-06-01 | Perspectives on the in vitro culture of filariae
A primary constraint in the culture of human filariae is in obtaining starting material—either microfilariae (mfs), which infect invertebrates, or third stage larvae (L3s), which are infective to humans. Cryopreservation methods which partially overcome this difficulty have been developed for both mfs and L3s. Complete development of mfs to L3s outside an intact host was obtained recently when mosquito thoraces infected byBrugia malayi (24 h after the bloodmeal) were maintained in vitro. In another recent study in which no host tissues were present, a semidefined culture medium was used to investigate the properties of reduced glutathione (GSH) that stimulate early development ofOnchocerca lienalis mfs. An extended cysteinyl backbone and a free sulfhydryl were identified as the key structural elements provided by GSH. Stimulation also required the presence of low and high molecular weight components of serum as well as oxygen. Molting ofOnchocerca spp. L3s to the fourth stage at the rate of 50 to 70% has been reported by several researchers. Key factors identified in those successes have been temperature and serum lot. Improved long-term viability occurred with cellular co-culture. Beneficial effects of co-culture were shown to be due both to cellular conditioning of the medium as well as to lowered dissolved oxygen levels as a result of cellular metabolism. With the use of cell-conditioned medium and decreased incubator oxygen levels, long-term viability ofOnchocerca larvae in culture exceeded that previously reported. Recently,Brugia malayi adults of both sexes were cultured from L3s using a semidefined medium supplemented with human serum. Many of these sexually matured adults mated and produced viable microfilariae.
1988-12-01 | Aspects of the life history of Cercopithifilaria johnstoni (Nematoda:Filarioidea)
Spratt D.M. and Haycock P. 1988. Aspects of the life history of Cercopithifilaria johnstoni (Nematoda:Filarioidea). International Journal for Parasitology18: 1087–1092. Cercopithifilaria johnstoni (Nematoda:Filarioidea) occurs in the subcutaneous connective tissues of a spectrum of native murid and marsupial hosts in Eastern Australia. Life cycle studies revealed that: (i) microfilaria occur in lymphatic capillaries and extravascular connective tissue of the dermis (= 'skin-inhabiting'), (ii) ixodid ticks, particularly Ixodes trichosuri, are intermediate hosts in nature, (iii) development from microfilariae to infective third-stage larva occurs only while the tick is off the host, that is, during ecdysis from larva to nymph or from nymph to adult. Transmission of C. johnstoni in a wild population of bush rats (Rattus fuscipes) occurred in summer and winter, and was associated with peaks in the number of larval and/or nymphal stages of ticks on rats. C. johnstoni was transmitted experimentally to bandicoots (Isoodon macrourus, Perameles nasuta), bush rats and laboratory rats (R. norvegicus), indirectly by subcutaneous inoculation of third-stage larvae and directly by tick feeding. The prepatent period was approximately 3 months and the longest duration of microfilariae in the ' skin' was more than 25 months. Dermal and ocular lesions were observed in R. fuscipes. The host-parasite relationship has the potential for development as an inexpensive and practical model for human onchocerciasis.
small molecules
2026-09-17 | Diethylcarbamazine: A review of its modes of action.
Filariases are neglected tropical diseases caused by Clade III parasitic nematodes transmitted by biting insects as microfilaria which mature into female and male adults in the host. One example of filariasis is lymphatic filariasis or elephantiasis, caused by three species of filaria: Brugia malayi, Wuchereria bancrofti, and/or Brugia timori. Elephantiasis results from the occlusion of lymphatic vessels by adult parasites and subsequent swelling of the limbs. It is a disfiguring disease that occurs in 120 million people worldwide. Another filarial disease is onchocerciasis caused by Onchocerca volvulus. Microfilaria of this parasite invade the eye producing corneal scarring and blindness. The infected female blackflies that transmit these microfilaria belong to the Simulium genus, and breed in fast flowing rivers. Onchocerciasis occurs near these rivers and gives rise to the common name of the disease, i.e., "river blindness." Diethylcarbamazine (HetrazanR) was described as effective for treating filariases over 75 years ago by Yellapragada Subbarow and collaborators and is currently still in use. Diethylcarbamazine is characterized by a simple but flexible structure that provides it with the ability to combine with several target proteins, and a complex mode of action with effects on both filarial parasites and hosts. This Chapter reviews new observations on the activation of Transient Receptor Potential (TRP) ion-channels of B. malayi and older observations on the mechanisms of action of diethylcarbamazine. Diethylcarbamazine has three major effects: 1) A direct activating effect on filaria TRP channels producing transient inhibition of motility; 2) Reduction of host and parasite PGI2 and PGE2 production, thereby reducing host immune suppression; and 3) Activation and adhesion of host granulocytes which attack the filaria. We emphasize recent observations that include activation of TRP channels by diethylcarbamazine, an underappreciated mode of action of this classic anthelmintic.
2026-08-31 | Epidemiological and entomological assessment of persistent onchocerciasis transmission after long-term ivermectin treatment in communities along the Kéllé river, Cameroon
Despite two decades of annual Community-Directed Treatment with Ivermectin (CDTI) in the Eséka health district, onchocerciasis transmission persists in frontline villages along the Kéllé River. This study assessed the current epidemiological and entomological status to guide elimination strategies. We conducted cross-sectional clinical and parasitological surveys in two first-line villages (Pouth-Kéllé and Mapan) during June and July 2021. Skin snips were examined for Onchocerca volvulus microfilariae, and clinical manifestations were assessed. Monthly blackfly collections by human landing catches (HLC) were performed at four river sites over one year. Flies were dissected to detect O. volvulus larvae. Microfilarial prevalence was 18.7% (14/75) in Pouth-Kéllé and 15.6% (5/32) in Mapan. Palpable nodules were found in 10% and 6.3% of adults, respectively, reflecting chronic lesions despite recent ivermectin distribution. Reduced visual acuity was frequent (46.7% in Pouth-Kéllé, 47% in Mapan) and was significantly associated with microfilarial positivity in Pouth-Kéllé ( p = 0.04). Entomological surveys yielded a total of 9,163 blackflies collected across the four capture sites, of which 6,036 were dissected to detect O. volvulus larvae. Analysis of biting rates showed that collected point I (P1) exhibited the highest annual biting rate (40,500 bites/person/year), with marked seasonality peaking in April. Transmission risk persisted at collected point II (P2 –annual transmission potential: 14.3 infective larvae/person/year) and collected point IV (P4 − 10.0 infective larvae/person/year). Onchocerciasis transmission remains active in the Kéllé River basin despite two decades of ivermectin treatment. These findings support the urgent need for complementary and/or alternative strategies to achieve elimination of onchocerciasis.
2026-08-15 | Sustained Drug Exposure Drives Efficacy in Mice: PK/PD Analysis of Corallopyronin A against Wolbachia using Physiologically Based Absorption Modeling.
Corallopyronin A (CorA) depletes essential Wolbachia endosymbionts of filarial nematodes and is therefore a promising candidate for treating the neglected tropical diseases lymphatic filariasis and onchocerciasis. To optimize anti-Wolbachia therapy, the pharmacokinetic/pharmacodynamic (PK/PD) relationship was investigated. Due to the intra-nematode and -cellular target, conventional minimal inhibitory concentration could not be determined. Instead, an iterative approach was used to define PD efficacy thresholds and compare them with IC₅₀/IC₉₀ values from infected cells. A physiologically based biopharmaceutics model (PBBM) was developed in GastroPlus®, incorporating physicochemical in vitro and in vivo parameters to predict PK in mice. A mechanistic dissolution model for a CorA-povidone suspension was implemented and verified with in vivo single dose PK data. Simulations provided trough and peak concentrations (Cmax), AUC and time above threshold for multiple dosing regimens. In vivo efficacy was assessed in a Litomosoides sigmodontis mouse infection model by quantifying Wolbachia burden. CorA showed potent in vitro activity (IC₅₀/ IC₉₀: 0.007/0.030 µg/mL). In vivo, fractionated dosing improved efficacy. Cmax poorly predicted treatment outcome, while trough concentration and AUC over iterative model dependent efficacy threshold correlated strongly with the Wolbachia reduction (R²: 0.89 and 0.81). These thresholds show strong concordance with the experimentally determined IC₅₀/IC₉₀ values. The duration of drug exposure above 2.25 µg/mL was the most accurate predictor of efficacy (R²: 0.93). Based on the PK/PD modeling, an effective mouse dose of 16 mg/kg BID was identified. These findings highlight the importance of sustained drug exposure for optimizing CorA regimens and will guide clinical development.
2026-08-12 | Assessing the efficacy of high-dose rifampicin plus albendazole against onchocerciasis.
Onchocerciasis, also known as river blindness, remains a public health challenge in tropical regions. Despite significant gains through mass drug administration (MDA) with ivermectin, the infection remains persistent in many endemic foci. While the disease burden has reduced, elimination may require alternative strategies, including macrofilaricidal therapies. Rifampicin (RIF) has demonstrated strong anti-Wolbachia activity in vitro and in animal models, but its clinical efficacy in humans remains uncertain. We conducted a phase II randomized, controlled trial in Ghana to evaluate the safety and efficacy of high-dose RIF (35 mg/kg/day) combined with albendazole (ALB, 400 mg/day) as an alternative treatment for onchocerciasis. The study randomized 120 infected participants into one of four arms: RIF + ALB for 14 days (TA1), RIF + ALB for 7 days (TA2), ALB alone for 14 days (TA3), and a No Treatment control group (TA4). Treatment efficacy, including Wolbachia and microfilariae (MF) depletion, adult worm vitality and embryogenesis were assessed following treatment at 4-, 18-, and 20-months. High-dose RIF + ALB was safe and well-tolerated, associated with only mild, transient adverse events. Treatment with RIF + ALB for 14 days reduced Wolbachia load in skin MF at 4 months (47.9%; p = 0.018). ALB monotherapy showed sustained reductions in skin microfilarial densities at the 18- and 20-month time points (p < 0.05). However, no macrofilaricidal effect or sustained Wolbachia depletion in adult worms was observed in any group. High-dose RIF + ALB is safe with limited macrofilaricidal efficacy in clinical settings, contrasting with the superiority observed from preclinical trials. ALB alone shows promise as an alternative microfilaricidal treatment to ivermectin or as a complementary regimen. The lack of sustained efficacy of RIF as an anti-Wolbachia regimen may reflect suboptimal dosing, highlighting the need for further optimization of RIF-based regimens for onchocerciasis treatment. PACTR202009704006025 (https://pactr.samrc.ac.za/Search.aspx). Date of trial registration: September 9, 2020.
2026-08-01 | Modelling the impact of mass drug administration with ivermectin or moxidectin on human onchocerciasis when there is sub-optimal response of parasites to treatment.
Onchocerciasis is a disease caused by the filarial nematode parasite Onchocerca volvulus and is transmitted by blackflies after they ingest larval offspring, microfilariae, found in the skin of infected people. The elimination of transmission within endemic communities in sub-Saharan Africa, the Americas, and Yemen depends on mass drug administration of ivermectin (MDAi) at high treatment coverage until the prevalence of the parasite in people or in blackflies reaches below a threshold value. In Africa, there are a number of communities where worms that are less susceptible to the effects of ivermectin, i.e., that are sub-optimally responding (SOR), appear to be contributing to the persistence of onchocerciasis despite high-coverage MDAi. We have incorporated this variation in an epidemiological model to explore how the presence of SOR worms impacts the prevalence of people with skin microfilariae, fitting the model to epidemiological data from a community in Ghana, Asubende, where SOR has been detected. Incorporating a cumulative effect of ivermectin into the model fits the data better than if no cumulative effect is assumed. Simulations indicate that elimination is possible under biannual MDAi even if SOR worms are present in the starting population unless the baseline prevalence is hyperendemic. In a hyperendemic region, elimination is predicted if there is no SOR, but when SOR worms are included in the model, elimination is not reached even after twenty years of biannual MDAi with a treatment coverage of 80%. Biannual MDAi increases the proportion of reproducing female worms that would be characterized as SOR compared to annual MDAi. However, when using mass drug administration with moxidectin (MDAm), elimination becomes possible with fewer rounds of MDA even if there are worms that suboptimally respond to moxidectin. Our results support concerns raised in the research community that SOR to ivermectin in O. volvulus could result in persistent transmission despite high-coverage, biannual MDAi, but that MDAm could pose a solution, should safety and efficacy trials support its distribution.
vaccines
2026-07-01 | Safety and immunogenicity of an adjuvanted human onchocerciasis vaccine candidate, OvMANE1: preclinical evaluation in a mice model.
Onchocerciasis, caused by the filarial worm Onchocerca volvulus, remains a major public health challenge because of the limitations of ivermectin-based control strategies, thereby highlighting the need for more innovative tools such as vaccines. This study investigated the safety and immunogenicity of a novel multi-epitope chimeric antigen, OvMANE1 formulated with Freund's adjuvant, in BALB/c mice. Mice were immunised at three time points of 2-week intervals, with blood collected at each point to measure antibody levels and immune cells. Adjuvanted-OvMANE1 exhibited a promising safety profile, revealing neither any physical signs of toxicity nor behavioural abnormalities. Immunological assays showed significant increases in total IgG absorbance (OD 450 nm) after the first (P = 0.0260) and final booster doses (P = 0.026). Total IgG (P = 0.0086) and IgG1 (P = 0.0465) absorbances also increased significantly over the study period, suggesting sustained humoral immunity. Moreover, cellular responses were significantly enhanced, with elevated leucocyte count (P = 0.0190) and increased lymphocyte activity (P = 0.0397) observed in the adjuvanted-OvMANE1 group compared to the control. Indeed, total leucocytes increased progressively from Day 0 to Day 39, with significant differences recorded in the test group between doses: Days 0-14 (P = 0.0043) and Days 14-28 (P = 0.0079). The pronounced production of relevant antibodies and induction of cellular immunity is indicative of a mixed Th1/Th2 response and antibody-dependent cellular cytotoxicity (ADCC) targeting O. volvulus L3 and/or other larval stages of the parasite. These results position OvMANE1 as a promising vaccine candidate against human onchocerciasis. However, further in vivo studies are needed to confirm and expand these findings.
2026-03-30 | Onchocerciasis overview: pathogenesis, clinical spectrum, and therapeutic challenges of a neglected tropical disease.
Onchocerciasis is still a major health burden in sub-Saharan Africa and Yemen, where many cases occur as control efforts face persistent obstacles, while smaller, well-defined transmission foci remain in Brazil and Venezuela. Caused by the filarial nematode Onchocerca volvulus and transmitted by blackflies, the disease causes progressive disability, economic loss, and hampers community development. Despite decades of mass drug administration with ivermectin, the inability of the drug to kill adult worms, increasing concerns over resistance, and the lack of effective vaccines continue to hinder elimination strategies. This review provides an overview of the disease, discussing its transmission dynamics, pathogenesis, clinical manifestations, diagnosis, and treatment. It also examines the immune-mediated responses that drive tissue damage and chronic morbidity, with an emphasis on skin and ocular complications. We highlight the need for rapid, non-invasive, and cost-effective diagnostic tools to enhance disease surveillance and assessment of treatment. Finally, we discuss the limitations of current therapies and recent progress in vaccine development, particularly subunit and multi-epitope vaccine candidates identified through reverse vaccinology approaches. Together, these insights reinforce the need for integrated strategies, combining improved diagnostics, novel treatments, and vaccines, to drive progress toward onchocerciasis elimination.
2025-10-23 | Vaccination against Onchocerca volvulus induces IgG-mediated protective immunity dependent on neutrophils and complement.
Onchocerciasis remains a significant cause of morbidity and economic loss in sub-Saharan Africa. Despite the existence of effective therapeutics, a prophylactic vaccine targeting the etiologic agent, Onchocerca volvulus, is needed to control ongoing disease and transmission. Mice were vaccinated against O. volvulus with a fusion of the recombinant antigens Ov-103 and Ov-RAL-2 (Ov-FUS-1) with Advax-CpG adjuvant. Immunized mice developed protective immunity with the killing of third-stage larvae (L3) within 36 h of challenge infection. IgG from immunized mice passively transferred protective immunity to naïve mice, indicating that antigen-specific IgG mediated parasite elimination. Neutrophils were the most abundant subset of immune cells recruited to the parasite microenvironment in vivo, and treating mice with a granulocyte-depleting antibody resulted in the total loss of immune-mediated larval killing. Analysis of neutrophil gene expression revealed that both vaccination and the presence of O. volvulus larvae were capable of modulating neutrophil transcriptional activity. The mechanism by which antigen-specific IgG and neutrophils collaborated to kill L3 was independent of Fcγ receptors. However, the elimination of complement component C3 prevented vaccine-induced protection, which suggests these components may interact through the complement system. This study describes a vaccine-induced mechanism of protective immunity against O. volvulus L3 dependent on IgG, neutrophils, and complement, highlighting an effective collaboration between the innate and adaptive arms of the immune system to control O. volvulus infection.
2025-05-02 | Safety and immunogenicity of an adjuvanted human onchocerciasis vaccine candidate, Ov MANE1: preclinical evaluation in mice model
Abstract Onchocerciasis, caused by the filarial worm Onchocerca volvulus, remains a major public health challenge due to the limitations of ivermectin-based control strategies, thereby, highlighting the need for more innovative tools like vaccines. This study investigated the safety and immunogenicity of a novel multi-epitope chimeric antigen, OvMANE1 formulated with Freund’s adjuvant, in BALB/c mice. Following mice immunization at three time points of 2-week intervals, adjuvanted-OvMANE1 exhibited a promising safety profile, revealing neither any physical signs of toxicity nor behavioural abnormalities. Immunological assays showed significant increases in total IgG levels after the first (p = 0.0260) and final booster doses (p = 0.026). Interestingly, total IgG (p = 0.0086) and IgG1 (p = 0.0465) levels also increased significantly over the study period highlighting the ability of OvMANE1 to sustain humoral immunity. Moreover, cellular responses were significantly enhanced, with elevated leukocyte count (p = 0.0190) and increased lymphocyte activity (p = 0.0397) observed in the adjuvanted-OvMANE1 group compared to the control. Indeed, total leukocytes increased progressively from day 0 to day 39, with significant differences recorded in the test group between doses: day 0 vs. day 14 (p = 0.0043) and day 14 vs. day 28 (p = 0.0079). The pronounced production of relevant antibodies and induction of cellular immunity strongly suggests that the antigen can elicit mixed Th1/Th2 responses and antibody-dependent cellular cytotoxicity (ADCC) targeting O. volvulus L3 and/or other larval stages of the parasite. These results clearly show the emergence of OvMANE1 as a promising vaccine candidate against human onchocerciasis. However, further studies to evaluate the antigens protective potential in other animal species are required.
2024-05-09 | Predictive Immunoinformatics Reveal Promising Safety and Anti-Onchocerciasis Protective Immune Response Profiles to Vaccine Candidates (Ov-RAL-2 and Ov-103) in Anticipation of Phase I Clinical Trials
Abstract Onchocerciasis is a devastating tropical disease that causes severe eye and skin lesions. As global efforts shift from disease control to elimination, prophylactic/therapeutic vaccines have emerged as alternative elimination tools. Notably, Ov -RAL-2 and Ov -103 antigens have shown great promise in preclinical studies and plans are underway for clinical trials. Here, we predict the immunogenicity and other vaccine-related parameters for both antigens using immunoinformatics, as potential vaccine candidates against onchocerciasis. The analysis reveals that both antigens exhibit a favourable safety profile, making them promising candidates poised for human trials. Importantly, in silico immune simulation forecasts heightened antibody production and sustained cellular responses for both vaccine candidates. Indeed, the antigens were predicted to harbour substantial numbers of a wide range of distinct epitopes associated with protective responses against onchocerciasis, as well as the potential for stimulating innate immune TLR-4 receptor recognition with Ov -103 exhibiting better structural efficiency and antigenicity with no homology to human proteins compared to Ov -RAL-2. Overall, we provide herein valuable insights for advancing the development of Ov -103 and RAL-2 vaccine candidates against onchocerciasis in humans. Author’s summary To address the significant impact of onchocerciasis, a tropical disease commonly known as river blindness, we have employed computational tools to assess the viability of two promising vaccine candidates, namely Ov -RAL-2 and Ov -103. Existing control strategies alone are insufficient to eliminate the disease. Our study utilises advanced immunoinformatics techniques to systematically evaluate the safety, antigenicity, and immunogenic properties of these antigens as potential vaccine candidates against onchocerciasis prior to human trials. Our analysis revealed that both vaccine candidates demonstrate favourable safety profiles and possess the capability to induce robust antibody responses and cellular immunity. Notably, we identified numerous distinct epitopes present within each vaccine candidate that are associated with protective immunity against onchocerciasis. The abundance of these epitopes suggests that both vaccine candidates have the potential to activate the immune system through diverse humoral and cellular response mechanisms. By providing these valuable insights, our research assists in guiding the development of Ov -103 and Ov -RAL-2 as effective vaccines against onchocerciasis. Ultimately, our findings contribute to the global endeavour to eliminate this debilitating disease and enhance the quality of life for the millions of affected individuals.
proteins
2022-04-01 | Development of a recombinant vaccine against human onchocerciasis.
Human onchocerciasis caused by the filarial nematode parasite Onchocerca volvulus remains a major cause of debilitating disease infecting millions primarily in Sub-Saharan Africa. The development of a prophylactic vaccine, along with mass drug administration, would facilitate meeting the goal of onchocerciasis elimination by 2030. Models used to study immunity to Onchocerca include natural infection of cattle with Onchocerca ochengi and O. volvulus infective third-stage larvae implanted within diffusion chambers in mice. A vaccine, comprised of two adjuvanted recombinant antigens, induced protective immunity in genetically diverse mice suggesting that it will function similarly in diverse human populations. These antigens were recognized by immune humans and also induced protective immunity against Brugia malayi. We describe the development of a fusion protein composed of the two vaccine antigens with the plan to test the vaccine in cows and non-human primates as a prelude to the initiation of phase 1 clinical trials. The adjuvanted O. volvulus vaccine composed of two antigens Ov-103 and Ov-RAL-2 was shown to be consistently effective at inducing protective immunity using multiple immune mechanisms. The vaccine is ready for further evaluation in other animal models before moving to clinical trials in humans.
2018-05-01 | Onchocerca - infected cattle produce strong antibody responses to excretory-secretory proteins released from adult male Onchocerca ochengi worms
The front line molecules from filarial worms and other nematodes or helminthes are their Excretory-Secretory (ES) products. Their interaction with the host cells, proteins and immune system accounts for the skin and eye pathology or hyposensitivity observed in human onchocerciasis. ES products and adult worms’ crude extracts from Onchocerca ochengi, a filarial nematode that infects the African zebu cattle, were utilized in the present study as a model for studying Onchocerca volvulus that causes river blindness in man. The ES products were generated from adult male and female worms in vitro and analyzed with poly acrylamide gel electrophoresis (PAGE) and enzyme-linked immunosorbent assay (ELISA) using sera from Onchocerca-infected cattle and humans. The cattle sera were collected from a herd that had been exposed for six years to natural transmission of Onchocerca spp. The expressed reactivity was evaluated and differences analyzed statistically using Kruskal-Wallis rank and Chi-square tests. The gel electrophoretic analyses of 156 ES products from O. ochengi female and male worms and of two somatic extracts from three females and 25 males revealed differences in the protein pattern showing pronounced bands at 15, 30–50 and 75 kDa for male ES proteins and 15, 25 and 40–75 kDa for somatic extracts, respectively and less than 100 kDa for female worms. Proteins in the ES products and somatic extracts from female and male Onchocerca ochengi worms were recognized by IgG in sera from both Onchocerca-exposed cattle and humans. Bovine serum antibodies reacted more strongly with proteins in the somatic extracts than with those in the ES products. Interestingly, the reaction was higher with male ES products than with ES products from female worms, suggesting that the males which migrate from one nodule to another are more exposed to the host immune system than the females which remain encapsulated in intradermal nodules. This study demonstrates that O. ochengi ES products and, in particular, extracts from male filariae may represent a good source of immunogenic proteins and potential vaccine candidates.
2016-07-07 | The Immunomodulatory Role of Adjuvants in Vaccines Formulated with the Recombinant Antigens Ov-103 and Ov-RAL-2 against Onchocerca volvulus in Mice
Background In some regions in Africa, elimination of onchocerciasis may be possible with mass drug administration, although there is concern based on several factors that onchocerciasis cannot be eliminated solely through this approach. A vaccine against Onchocerca volvulus would provide a critical tool for the ultimate elimination of this infection. Previous studies have demonstrated that immunization of mice with Ov-103 and Ov-RAL-2, when formulated with alum, induced protective immunity. It was hypothesized that the levels of protective immunity induced with the two recombinant antigens formulated with alum would be improved by formulation with other adjuvants known to enhance different types of antigen-specific immune responses. Methodology/ Principal Findings Immunizing mice with Ov-103 and Ov-RAL-2 in conjunction with alum, Advax 2 and MF59 induced significant levels of larval killing and host protection. The immune response was biased towards Th2 with all three of the adjuvants, with IgG1 the dominant antibody. Improved larval killing and host protection was observed in mice immunized with co-administered Ov-103 and Ov-RAL-2 in conjunction with each of the three adjuvants as compared to single immunizations. Antigen–specific antibody titers were significantly increased in mice immunized concurrently with the two antigens. Based on chemokine levels, it appears that neutrophils and eosinophils participate in the protective immune response induced by Ov-103, and macrophages and neutrophils participate in immunity induced by Ov-RAL-2. Conclusions/Significance The mechanism of protective immunity induced by Ov-103 and Ov-RAL-2, with the adjuvants alum, Advax 2 and MF59, appears to be multifactorial with roles for cytokines, chemokines, antibody and specific effector cells. The vaccines developed in this study have the potential of reducing the morbidity associated with onchocerciasis in humans.
2015-09-14 | A Proteomic Analysis of the Body Wall, Digestive Tract, and Reproductive Tract of Brugia malayi
Filarial worms are parasitic nematodes that cause devastating diseases such as lymphatic filariasis (LF) and onchocerciasis. Filariae are nematodes with complex anatomy including fully developed digestive tracts and reproductive organs. To better understand the basic biology of filarial parasites and to provide insights into drug targets and vaccine design, we conducted a proteomic analysis of different anatomic fractions of Brugia malayi, a causative agent of LF. Approximately 500 adult female B. malayi worms were dissected, and three anatomical fractions (body wall, digestive tract, and reproductive tract) were obtained. Proteins from each anatomical fraction were extracted, desalted, trypsinized, and analyzed by microcapillary reverse-phase liquid chromatography-tandem-mass spectrometry. In total, we identified 4,785 B. malayi proteins. While 1,894 were identified in all three anatomic fractions, 396 were positively identified only within the digestive tract, 114 only within the body wall, and 1,011 only within the reproductive tract. Gene set enrichment analysis revealed a bias for transporters to be present within the digestive tract, suggesting that the intestine of adult filariae is functional and important for nutrient uptake or waste removal. As expected, the body wall exhibited increased frequencies of cytoskeletal proteins, and the reproductive tract had increased frequencies of proteins involved in nuclear regulation and transcription. In assessing for possible vaccine candidates, we focused on proteins sequestered within the digestive tract, as these could possibly represent "hidden antigens" with low risk of prior allergic sensitization. We identified 106 proteins that are enriched in the digestive tract and are predicted to localize to the surface of cells in the the digestive tract. It is possible that some of these proteins are on the luminal surface and may be accessible by antibodies ingested by the worm. A subset of 27 of these proteins appear especially promising vaccine candidates as they contain significant non-cytoplasmic domains, only 1–2 transmembrane domains, and a high degree of homology to W. bancrofti and/or O. volvulus.
2015-09-11 | Immune recognition of excretory and secretory products of the filarial nematode Onchocerca ochengi in cattle and human sera.
Excretory-secretory (ES) products of nematodes and other helminths are the first molecules to interact with cell surfaces and soluble proteins within the host. In the present study, ES products of the filarial nematode Onchocerca ochengi were investigated as a model for Onchocerca volvulus, the causative agent of river blindness. These products were collected from adult and larval stages in vitro over a period of 7 days, to compare their immunological recognition in cattle and human sera, infected with species of Onchocerca. From the 156 sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) ES products or extracts, protein bands showed different patterns between female and male products. A comparison of antibody recognition of the different ES products by sera from infected cattle and humans, when analysed by enzyme-linked immunosorbent assay (ELISA), revealed a relatively higher reactivity of the female somatic extract to human and cattle sera compared to ES products of both genders. Nevertheless, similar reactivity of the O. ochengi male and female ES products to human and cattle sera was noticed. As a result, the interaction of ES products with the surface of the host and immune system often led to host responses, including the generation of antibodies. The O. ochengi ES products are therefore good sources of potential immunogenic proteins. The identification of these ES products is in progress, with the aim of developing vaccine candidates against human onchocerciasis.
gene therapies
2026-09-06 | Spatial and seasonal dynamics of Simulium damnosum s.l. and entomological indicators of onchocercosis in the provinces of Huambo and Cuanza-Sul in Angola.
Onchocerciasis remains a public health problem in Angola. Despite the implementation of onchocerciasis control programs based on mass treatment with ivermectin, current entomological data remain limited, making it difficult to accurately assess the potential risk of transmission. Our objectives were to analyze the spatial and seasonal dynamics of Simulium damnosum s.l. and the main entomological indicators of onchocerciasis in the provinces of Huambo and Cuanza Sul, Angola, to assess the potential entomological risk of transmission. We captured black flies using the human bait capture method for 48 days between July and October 2025. Analyses of entomological indicators included abundance, monthly bite rate (MBR), parity, seasonality, daily activity, and monthly transmission potential (MTP). Morphological identification of specimens was performed according to standard taxonomic keys. A total of 6.038 black flies were captured during the study period, including 3.615 in Huambo and 2.423 in Cuanza Sul. All black flies belonged to species of the savanna group. The average BMR was high (1.890 bites/person/month), with significant seasonal variations. The overall parity rate reached 59%, significantly higher in Cuanza Sul. No black flies infected with Onchocerca volvulus were found, resulting in a zero PMT at all study sites. Despite high vector density and relatively old black fly populations, the absence of transmission suggests a reduction in onchocerciasis transmission in the studied regions. These results demonstrate the importance of maintaining regular entomological surveillance to prevent potential transmission in an ecological context favorable to the vector.
2026-03-29 | Programmatic implications of the efficiency of uptake of Onchocerca volvulus microfilaria by Simulium sp. vectors.
The current global aim for onchocerciasis is to eliminate transmission of infection by administering ivermectin once or biannually. However, when ivermectin treatment is given annually for 9-10 years, some individuals still carry low mf levels, which may allow continued transmission. 1608 newly emerged Simulium sanctipauli (Pra form) flies were fed on 35 volunteers at four different times (0, 8, 90, 365 days) after treatment with ivermectin, with initial dermal microfilarial loads ranging from 0 to >30 Onchocerca volvulus mf/mg skin. Ten days after feeding, the number and load of mf in these flies were assessed by dissection. Notably, even at the lowest skin snip mf densities-including those showing zero infection flies can still ingest O. volvulus microfilariae and become infected; 29% of the 1608 fed flies picked up microfilariae. The lowest skin mf levels were recorded on Day 90 after treatment, at which time vector mf uptake increased by 21% with every unit increase in skin mf density (p<0.000). Very low dermal mf levels can still support parasite transmission. Consequently, widespread low O. volvulus infection in human populations with highly productive vector-breeding sites could significantly affect efforts to eliminate transmission.
2026-02-27 | Integrated serosurveillance to assess disease elimination in coastal Ecuador: onchocerciasis, yaws, and trachoma.
Testing blood samples with multiplex bead assays can assess elimination and identify residual foci of transmission for multiple pathogens simultaneously. In Ecuador, onchocerciasis and yaws are presumed eliminated, and the status of trachoma is unknown. We assessed their elimination status by measuring IgG antibodies in children 6-24 months. In a birth cohort of 404 children measured between 2021-2024 in Esmeraldas province, Ecuador, we tested dried blood spots at ages 6, 9, 12, 18, and 24 months using a multiplex IgG assay that included antigens to Onchocerca volvulus (Ov16), Treponema pallidum (rp17, tmpa), and Chlamydia trachomatis (Pgp3, Ct694). We estimated seroprevalence and incident seroconversion rates across an urban-rural gradient. Of 404 children enrolled, 370 contributed 1,606 samples. Seroprevalence was near zero for onchocerciasis (0.4%, 95% CI: 0.2% to 0.8%) and yaws (0.2%, 95% CI: 0.0% to 0.5%). Conversely, C. trachomatis Pgp3 seroprevalence increased along the urban-rural gradient from Esmeraldas city (3.4%, 95% CI: 1.8% to 5.8%) to remote, river-accessible rural villages (22.4%, 95% CI: 16.0% to 30.1%), and incident seroconversion was common in rural villages (16.1 per 100 child-years, 95% CI: 11.3 to 21.9). Serologic surveillance found no evidence of O. volvulus or T. pallidum transmission, consistent with elimination. High Pgp3 seroconversion rates suggest ongoing C. trachomatis transmission in rural villages. Results highlight the value of integrated serologic surveillance and motivate in-depth trachoma surveillance in Esmeraldas.
2026-02-26 | Exploring potential pathogenesis mechanisms of onchocerciasis-associated epilepsy through cerebrospinal fluid analysis of children with complex febrile seizures: a pilot study in Aketi, Democratic Republic of the Congo.
Onchocerciasis, commonly known as river blindness, is a parasitic disease caused by Onchocerca volvulus affecting millions predominantly in sub-Saharan Africa. Robust epidemiological evidence points to a clinical relationship between onchocerciasis and epilepsy, a condition termed onchocerciasis-associated epilepsy (OAE). Despite extensive research and various successful elimination programmes over the past decades, the pathogenesis of OAE is still unknown. Current hypotheses propose that O. volvulus microfilaria, their excretory-secretory products or the newly discovered filarial O. volvulus RNA virus 1 (OVRV1) virus may traverse the blood-brain barrier, triggering seizures or immune responses that result in neurological damage. However, direct evidence of microfilaria or their DNA in cerebrospinal fluid (CSF) or brain tissue remains elusive, likely due to immune-mediated parasite clearance. Additionally, investigations into the potential neurotoxicity of these novel filarial viruses have yet to be pioneered. This prospective cohort study will involve 100 ivermectin-naïve children aged 2-5 years, recruited from rural communities in the Aketi health zone, located in the Democratic Republic of Congo. This region is known to be an onchocerciasis-endemic area with a high prevalence and transmission of OAE, despite years of community-directed treatment with ivermectin. Lumbar punctures (LP) will be performed in children presenting with complex febrile seizures according to WHO's paediatric guidelines. CSF samples will be examined for white blood cells, protein levels, glycorrhachia, microfilaria, OVRV1 and O. volvulus biomarkers. Children will be followed annually, monitoring the development of epilepsy and O. volvulus infection. This approach aims to elucidate the presence of O. volvulus and OVRV1 in the brain and their role in the pathogenesis of epileptic seizures and the myriad of clinical symptoms observed in OAE. The protocol has been approved by the Ethics Committee of the University of Kisangani (UNIKIS/CE/KGB/001/2025) and the University of Antwerp (project ID 7323-Edge n/a-BUN B3002025000078). Written informed consent will be obtained from all parents and/or legal guardians of children for whom an LP is considered. Findings will be disseminated at national and international levels via meetings and peer-reviewed open-source publications. Study data will be stored in an open repository. Pan African Clinical Trials Registry (PACTR202507670131109).
2025-08-08 | Physiological and Behavioral Effects of Onchocerca ochengi Infection in Gerbils: Implications for Onchocerciasis-Associated Epilepsy Research.
PURPOSE: This study aimed to investigate whether Onchocerca ochengi infection directly causes epilepsy. Although O. ochengi—a cattle parasite phylogenetically related to O. volvulus—shares biological similarities with its human counterpart, it has not been epidemiologically linked to epilepsy in bovines, unlike O. volvulus, which has been associated with onchocerciasis-associated epilepsy in humans. No prior experimental studies have established a causal relationship between onchocerciasis and epilepsy. METHODS: Gerbils were surgically implanted with O. ochengi worm masses (test group) or underwent sham operations (control group) to assess the infection’s effects. Survival rates were monitored post-implantation, and behavioral assessments were conducted on days 15–19 using the elevated plus maze, open-field, object recognition, and hanging wire tests. On day 21, the gerbils were sacrificed, and their body and organ weights were recorded, along with an analysis of worm mass survival. RESULTS: Implantation of 15 worm masses resulted in 100% mortality in the test group. When 10 worm masses were implanted, 53.3% of gerbils died, while all control gerbils survived. By day 21, an average of 1.4 out of 10 implanted worm masses remained viable, with a viability score of 93.3%. Test gerbils exhibited significant reductions in overall body weight and increased spleen weight compared to controls. However, behavioral tests revealed no significant differences between the two groups. CONCLUSION: While O. ochengi worm masses caused notable physical effects, including increased mortality and altered body and organ weights, no conclusive evidence was found linking the infection to behavioral changes indicative of epilepsy. Further research is necessary to explore the potential association between onchocerciasis and epilepsy development.
other
2022-10-17 | NKp46+ natural killer cells develop an activated/memory-like phenotype and contribute to innate immunity against experimental filarial infection.
Lymphatic filariasis and onchocerciasis are major neglected tropical diseases affecting over 90 million people worldwide with painful and profoundly disfiguring pathologies (such as lymphoedema or blindness). Type 2 inflammation is a hallmark of filarial nematode tissue infection and is implicated both in eosinophil dependent immunity and lymphatic or ocular immunopathologies. Type-2 innate lymphoid cells (ILC2) are known to play an important role in the initiation of type 2 inflammation in helminth infection. We therefore tracked comparative IL-12Rβ2+ ILC1, ST2+ ILC2 and NKp46+ natural killer (NK) innate lymphoid cell population expansions during Brugia malayi experimental peritoneal filarial infections using either immunocompetent or immunodeficient mice. In immunocompetent BALB/c animals, NKp46+ NK cells rapidly expanded representing over 90% of the ILC population in the first week of infection, whereas, surprisingly, ST2+ ILC2 failed to expand. NKp46+ NK cell expansions were confirmed in RAG2 deficient mice lacking adaptive immunity. Ablation of the NKp46+ NK cell compartment in RAG2 common gamma chain (gc) mice led to increased susceptibility to chronic adult B. malayi infection. This data was recapitulated using an Onchocerca ochengi male worm peritoneal implant model. When NKp46+ NK cells were depleted in RAG2 deficient mice using anti-NKp46 or asialo GM1 antibody injections over the first five weeks of B. malayi infection, susceptibility to adult B. malayi infection was significantly increased by 2-3 fold with concomitant impairment in eosinophil or neutrophil recruitments. Finally, we demonstrate that in RAG2 deficient mice, drug clearance of a primary adult B. malayi infection followed by challenge infection leads to resistance against early larval B. malayi establishment. This innate resistance is associated with bolstered NK and eosinophils whereby NKp46+ NK cells express markers of memory-like/enhanced activation (increased expression of interferon gamma and Ly6C). Our data promotes a novel functional role for NKp46+ NK cells in immunoprotection against experimental primary and secondary filarial infection which can proceed in the absence of adaptive immune regulation.
1997-05-01 | Production of both IFN-gamma and IL-5 by Onchocerca volvulus S1 antigen- specific CD4+ T cells from putatively immune individuals
Protective immunity to the parasitic nematode Onchocerca volvulus (Ov) appears to be directed against molecules of invading L3 larvae. In this study, the cellular immune reaction to such an Ov L3 protein (S1) which is protective in an animal model was analyzed using peripheral blood mononuclear cells (PBMC) of individuals from a hyperendemic area in West Africa who were exposed to Ov but remained free from disease ('putatively immune individuals'). Despite seronegativity of these individuals against S1, proliferation of PBMC was inducible, allowing generation of an S1-specific T cell line which produced IFN-gamma upon stimulation with both Ov lysate and S1. However, S1 induced significantly more IL-5 than Ov lysate. S1-specific, DQ6 (DQA1*0103/DQB1*0603)-restricted T cell clones were generated which reacted against synthetic peptides comprising amino acids 99-111 of S1. These clones, which are the first generated against a recombinant fllarial antigen, produced both IFN-gamma and IL-5 as well as little IL-4, suggestive of a Th0-like phenotype. In conclusion, in putative immunity, reactivity against a particular parasite protein can be detectable on the level of T but not B cells. Induction of both IFN-gamma and IL-5 by S1 suggests that it may trigger macrophage plus eosinophil dependent killing of L3 in vivo. The identification of a likely DQ6 (DQA1*0103/DQB1*0603)-restricted T cell epitope may be of more general relevance, given that allele combinations of DQ6, including DQA1*0103/DQB1*0603, are negatively associated with diabetes mellitus.
1994-03-01 | Cattle, worms and zooprophylaxis
Epidemiological studies in North Cameroon indicate that a high population density of cattle in relation to man protects from severe onchocerciasis. In the following, we present a mathematical model which allows to study the effects of zoophily of the vectors, of concomitant immunity in the human population and of cross-protective immunity caused by the infective larvae of a bovine parasite, Onchocerca ochengi, inoculated into man by Simulium damnosum s.l. Besides this influence on onchocerciasis, cattle also play a major role in the epidemiology of malaria (zooprophylaxis through vector dilution) and schistosomiasis (protection by crossreactive concomitant immunity).
1991-06-01 | Perspectives on the in vitro culture of filariae
A primary constraint in the culture of human filariae is in obtaining starting material—either microfilariae (mfs), which infect invertebrates, or third stage larvae (L3s), which are infective to humans. Cryopreservation methods which partially overcome this difficulty have been developed for both mfs and L3s. Complete development of mfs to L3s outside an intact host was obtained recently when mosquito thoraces infected byBrugia malayi (24 h after the bloodmeal) were maintained in vitro. In another recent study in which no host tissues were present, a semidefined culture medium was used to investigate the properties of reduced glutathione (GSH) that stimulate early development ofOnchocerca lienalis mfs. An extended cysteinyl backbone and a free sulfhydryl were identified as the key structural elements provided by GSH. Stimulation also required the presence of low and high molecular weight components of serum as well as oxygen. Molting ofOnchocerca spp. L3s to the fourth stage at the rate of 50 to 70% has been reported by several researchers. Key factors identified in those successes have been temperature and serum lot. Improved long-term viability occurred with cellular co-culture. Beneficial effects of co-culture were shown to be due both to cellular conditioning of the medium as well as to lowered dissolved oxygen levels as a result of cellular metabolism. With the use of cell-conditioned medium and decreased incubator oxygen levels, long-term viability ofOnchocerca larvae in culture exceeded that previously reported. Recently,Brugia malayi adults of both sexes were cultured from L3s using a semidefined medium supplemented with human serum. Many of these sexually matured adults mated and produced viable microfilariae.
1988-12-01 | Aspects of the life history of Cercopithifilaria johnstoni (Nematoda:Filarioidea)
Spratt D.M. and Haycock P. 1988. Aspects of the life history of Cercopithifilaria johnstoni (Nematoda:Filarioidea). International Journal for Parasitology18: 1087–1092. Cercopithifilaria johnstoni (Nematoda:Filarioidea) occurs in the subcutaneous connective tissues of a spectrum of native murid and marsupial hosts in Eastern Australia. Life cycle studies revealed that: (i) microfilaria occur in lymphatic capillaries and extravascular connective tissue of the dermis (= 'skin-inhabiting'), (ii) ixodid ticks, particularly Ixodes trichosuri, are intermediate hosts in nature, (iii) development from microfilariae to infective third-stage larva occurs only while the tick is off the host, that is, during ecdysis from larva to nymph or from nymph to adult. Transmission of C. johnstoni in a wild population of bush rats (Rattus fuscipes) occurred in summer and winter, and was associated with peaks in the number of larval and/or nymphal stages of ticks on rats. C. johnstoni was transmitted experimentally to bandicoots (Isoodon macrourus, Perameles nasuta), bush rats and laboratory rats (R. norvegicus), indirectly by subcutaneous inoculation of third-stage larvae and directly by tick feeding. The prepatent period was approximately 3 months and the longest duration of microfilariae in the ' skin' was more than 25 months. Dermal and ocular lesions were observed in R. fuscipes. The host-parasite relationship has the potential for development as an inexpensive and practical model for human onchocerciasis.
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Drug Discovery Landscape
4 orphan drug designations for Onchocerciasis, including 1 approved therapy.
4 orphan drug designations for Onchocerciasis, including 1 approved therapy.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
4¿-(p-fluorobenzyl)tylosin A | small molecules | FDA | AbbVie Inc. | |
emodepside | small molecules | FDA | Bayer HealthCare Pharmaceuticals, Inc. | |
flubendazole | small molecules | FDA | — | Janssen Research & Development, LLC |
moxidectin | small molecules | FDA | Approved | Medicines Development for Global Health Limited |
“Terminated” – programs with discontinued clinical trials, or with no updates reported for 5 years after completion or 12 years after the last trial started.
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