Onchocerciasis Infection Research Articles

Efficacy and safety of emodepside compared with albendazole in adolescents and adults with hookworm infection in Pemba Island, Tanzania: a double-blind, superiority, phase 2b, randomised controlled trial

Human hookworm is a cause of enormous global morbidity. Current treatments have insufficient efficacy and their extensive and indiscriminate distribution could also result in drug resistance. Therefore, we tested the efficacy and safety of emodepside, a strong anthelmintic candidate that is currently undergoing clinical development for onchocerciasis and soil-transmitted helminth infections. We conducted a double-blind, superiority, phase 2b, randomised controlled clinical trial comparing emodepside and albendazole. Participants in the emodepside group received six 5 mg tablets of emodepside (totalling 30 mg) and one placebo; participants in the albendazole group received one 400 mg tablet of albendazole and six placebos. Participants were recruited from four endemic villages and three secondary schools in Pemba Island, Tanzania. Participants aged 12-60 years were eligible for treatment if they were positive for hookworm infection, and they had 48 or more eggs per gram from four Kato-Katz thick smears and at least two slides had more than one hookworm egg present. Participants' treatment allocation was stratified by infection intensity and efficacy was measured by cure rate: participants who were hookworm positive and became hookworm negative after treatment. Adverse events were reported at 3 h, 24 h, 48 h, and 14-21 days post-treatment. The trial is registered at ClinicalTrials.gov, NCT05538767. From Sept 15 to Nov 8, 2022, and from Feb 15 to March 15, 2023, 1609 individuals were screened for hookworm. Of these, 293 individuals were treated: 147 with albendazole and 146 with emodepside. Emodepside demonstrated superiority, with an observed cure rate against hookworm of 96·6%, which was significantly higher compared with albendazole (cure rate 81·2%, odds ratio 0·14, 95% CI 0·04-0·35; p=0·0001). The most common adverse event in the emodepside treatment group was vision blur at 3 h after treatment (57 [39%] of 146). Other common adverse events were vision blur at 24 h after treatment (55 [38%]), and headache and dizziness at 3 h after treatment (55 [38%] for headache and 43 [30%] for dizziness). In the emodepside treatment group, 298 (93%) of the 319 adverse events were mild. The most commonly reported adverse events in the albendazole treatment group were headache and dizziness at 3 h after treatment (27 [18%] of 147 for headache and 14 [10%] for dizziness). No serious adverse events were reported. This phase 2b clinical trial confirms the high efficacy of emodepside against hookworm infections, solidifying emodepside as a promising anthelmintic candidate. However, although the observed safety events were generally mild in severity, considerations must be made to balance the strong efficacy outcomes with the increased frequency of adverse events compared with albendazole. European Research Council.

Dementia Prevalence and Onchocerca volvulus Infection among Rural Elderly Persons in the Ntui Health District, Cameroon: A Population-Based Study.

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

Global stability analysis and modelling onchocerciasis transmission dynamics with control measures

ABSTRACT Background: Onchocerciasis infection is one of the neglected tropical diseases targeted for eradication by 2030. The disease is usually transmitted to humans through the bites of black flies. These black flies mostly breed near well-oxygenated fast-running water bodies. The disease is common in mostly remote agricultural villages near rivers and streams. Objective: In this study, a deterministic model describing the infection dynamics of human onchocerciasis disease with control measures is presented. Methods: We derived the model’s reproductive number and used a stability theorem of a Metzler matrix to show that disease-free equilibrium is both locally and globally asymptotically stable whenever the reproductive number is less than one. Parameter contribution was conducted using sensitivity analysis. The model endemic equation is shown to be a cubic polynomial in the presence of infected immigrants and a quadratic form in their absence. Results: When the inflow of infected immigrants is null, the model endemic equation may admit a unique equilibrium if the reproductive number is greater than one, or admits multiple endemic equilibria if the reproductive number is less than unity. We carried out a sensitivity analysis to identify the significant parameters that contribute to onchocerciasis spread. Conclusion: Onchocerciasis disease can be eradicated if the importation of infected immigrants is properly monitored. The integration of the One Health concept in the public health system is key in tackling the emergence and spread of diseases.

Progress towards elimination of onchocerciasis in the Region du Sud-Ouest of Burkina Faso which was previously subject to a recrudescence event after vector control.

The Sud-Ouest region of Burkina Faso (especially the Bougouriba valley) has been historically problematic with respect to onchocerciasis control, with a recrudescence of infections after vector control carried out the WHO Onchocerciasis Control Programme was halted in 1989. After 1996, mass drug administration of ivermectin was instigated to control the recrudescence so that it would no longer constitute a public health problem. However, in 2010 WHO changed its recommended policy from control to elimination, and in 2013 biannual Community-Directed Treatment with Ivermectin (CDTI) was instigated. Epidemiological surveys were carried-out in 2011 and 2018 to determine whether CDTI was producing a decline in infection levels and progress towards elimination. A cross-sectional study was conducted across 20 villages in four health districts in 2011 and 29 villages in 2018. Individuals aged five years and above were examined by skin-snip, and the prevalence and microfilarial load was determined for each village. In 2011, 75% of villages had some infections and 20% had prevalences >5%, with a mean prevalence across all villages of 2.63% (range 0.0-9.7%), and community microfilarial load ranging from 0 to 0.25 microfilariae per biopsy. In 2018, nine villages (= 31% of total) had some infections, with prevalences ranging from 0.41% to 3.54%, and a mean prevalence across all villages of 0.37%. Community microfilarial load ranged from 0 to 0.1. Amongst those people found to be microfilarial positive, 87% had a history of migration. The endemicity of onchocerciasis infection in the Sud-Ouest region has declined to low levels and seems to be progressing towards elimination. Our findings indicated that biannual CDTI is having good effect, but it should continue for a number of years to ensure elimination of transmission. However, progress towards elimination has a troublesome history in this region, and it would be advisable to select more sentinel villages to have confidence in any future epidemiological and entomological surveys, especially Stop-MDA surveys. With positive individuals migrating between countries, cross-border collaboration needs more attention to ensure effective treatment for onchocerciasis elimination.

Mapping the Burden of Visual Impairment Due to Onchocerciasis Infection in Central Africa from 1990 to 2019.

Mapping the Burden of Visual Impairment Due to Onchocerciasis Infection in Central Africa from 1990 to 2019.

Geospatial distribution and predictive modeling of onchocerciasis in Ogun State, Nigeria.

Onchocerciasis caused by infection with Onchocerca volvulus is a disease of public health importance and is highly associated with disability. As Nigeria is aiming at eliminating onchocerciasis by 2030, there is a need to develop newer tools to map disease prevalence and identify environmental factors driving disease prevalence, even in places that have not been previously targeted for preventive chemotherapy. This study produced predictive risk-maps of onchocerciasis in Ogun State. Georeferenced onchocerciasis infection data obtained from a cross-sectional survey at 32 locations between March and July 2015 together with remotely-sensed environmental data were analyzed using Ecological Niche Models (ENM). A total of 107 field occurrence points for O. volvulus infection were recorded. A total of 43 positive occurrence points were used for modelling. ENMs were used to estimate the current geographic distribution of O. volvulus in Ogun State. Maximum Entropy distribution modeling (MaxEnt) was used for predicting the potential suitable habitats, using a portion of the occurrence records. A total of 19 environmental variables were used to model the potential geographical distribution area under current climatic conditions. Empirical prevalence of 9.3% was recorded in this study. The geospatial distribution of infection revealed that all communities in Odeda Local Government Area (a peri-urban LGA) showed remarkably high prevalence compared with other LGAs. The predicted high-risk areas (probability > 0.8) of O. volvulus infection were all parts of Odeda, Abeokuta South, and Abeokuta North, southern part of Imeko-Afon, a large part of Yewa North, some parts of Ewekoro and Obafemi-Owode LGAs. The estimated prevalence for these regions were >60% (between 61% and 100%). As predicted, O. volvulus occurrence showed a positive association with variables reflecting precipitation in Ogun State. Our predictive risk-maps has provided useful information for the elimination of onchocerciais, by identifying priority areas for delivery of intervention in Ogun State, Nigeria.

Evaluating the impact of alternative intervention strategies in accelerating onchocerciasis elimination in an area of persistent transmission in the West Region of Cameroon.

Alternative strategies are recommended to accelerate onchocerciasis elimination in problematic areas including areas where annual ivermectin (IVM) distributions are unable to interrupt transmission. The aim of this study was to accelerate progress towards elimination in the Massangam health district, West Region of Cameroon where impact evaluations demonstrated ongoing transmission of onchocerciasis infection and high microfilaria (mf) prevalence despite more than 20 years of annual IVM distribution. Parasitological, entomological, and breeding site surveys were conducted in 2015 delineating a focus of high transmission and identified three communities with high mf prevalence. Individuals in these communities were screened for mf yearly for a period of two years and those positive treated each year with doxycycline 100mg daily for five weeks. In addition, surrounding communities were given biannual IVM. Temephos-based applications were performed once a week for 10 consecutive weeks on Simulium damnosum s.l. breeding sites. Parasitological and entomological assessments were conducted after two years of implementation and findings compared with 2015 baseline. Alternative strategies accelerated progress towards elimination through a significant mf reduction (χ2: 40.1; p<0.001) from 35.7% (95%CI: 29.0-42.8) to 12.3% (95%CI, 9.0-16.4). Reductions were furthermore recorded over a longer period, with a reduction of prevalence of 29.0% under AIS in 2017-2019 compared to 14.6% with IVM in 2011-2015; and by 23.2% following the two years of alternative strategies compared to 20.3% reduction over 15 years of treatment with IVM (1996-2011). Entomological assessment demonstrates that transmission is still ongoing despite the reduction in mf which is expected in an environment with complex breeding sites and open transmission zones, i.e., where migration of flies or humans to and from neighbouring areas is common. This study provides evidence that alternative strategies are feasible and effective and should be considered in areas where transmission is sustained throughout long term uninterrupted MDA with IVM. However, there is need to consider wider transmission zones, and further explore optimal timing of larviciding with treatment to impact transmission.

The prevalence of onchocerciasis in Africa and Yemen, 2000–2018: a geospatial analysis

BackgroundOnchocerciasis is a disease caused by infection with Onchocerca volvulus, which is transmitted to humans via the bite of several species of black fly, and is responsible for permanent blindness or vision loss, as well as severe skin disease. Predominantly endemic in parts of Africa and Yemen, preventive chemotherapy with mass drug administration of ivermectin is the primary intervention recommended for the elimination of its transmission.MethodsA dataset of 18,116 geo-referenced prevalence survey datapoints was used to model annual 2000–2018 infection prevalence in Africa and Yemen. Using Bayesian model-based geostatistics, we generated spatially continuous estimates of all-age 2000–2018 onchocerciasis infection prevalence at the 5 × 5-km resolution as well as aggregations to the national level, along with corresponding estimates of the uncertainty in these predictions.ResultsAs of 2018, the prevalence of onchocerciasis infection continues to be concentrated across central and western Africa, with the highest mean estimates at the national level in Ghana (12.2%, 95% uncertainty interval [UI] 5.0–22.7). Mean estimates exceed 5% infection prevalence at the national level for Cameroon, Central African Republic, Democratic Republic of the Congo (DRC), Guinea-Bissau, Sierra Leone, and South Sudan.ConclusionsOur analysis suggests that onchocerciasis infection has declined over the last two decades throughout western and central Africa. Focal areas of Angola, Cameroon, the Democratic Republic of the Congo, Ethiopia, Ghana, Guinea, Mali, Nigeria, South Sudan, and Uganda continue to have mean microfiladermia prevalence estimates exceeding 25%. At and above this level, the continuation or initiation of mass drug administration with ivermectin is supported. If national programs aim to eliminate onchocerciasis infection, additional surveillance or supervision of areas of predicted high prevalence would be warranted to ensure sufficiently high coverage of program interventions.

Relationship between skin snip and Ov16 ELISA: Two diagnostic tools for onchocerciasis in a focus in Cameroon after two decades of ivermectin-based preventive chemotherapy.

BackgroundOnchocerciasis elimination currently relies on repeated ivermectin-based preventive chemotherapy. Current World Health Organization’s guidelines strongly recommend, though with low evidence of certainty, the use of Ov16 serology testing in children younger than 10 years old to assess whether mass drugs administration can be safely stopped. Therefore, more evidences are needed to support the use of this marker as sero-evaluation tool. This study aimed at determining the relationship between microfilaridermia and anti-Ov16 IgG4, and their variation according to age, gender and ivermectin intake history.MethodologyA cross-sectional survey was conducted in an area where ivermectin-based MDA has been implemented since more than 20 years. A questionnaire was used to record ivermectin intake history for the last 5 years. All volunteers aged ≥2 years were tested for microfilaridermia. IgG4 antibodies against Ov16 antigen were determined using the Standard Diagnostic Ov16 IgG4 ELISA kits and the recombinant anti-Ov16 AbD19432 antibodies. Prevalences, microfilaridermia counts and IgG4 concentrations were compared with regards to age, gender and history of ivermectin intake.Principal findingsThe prevalence of skin microfilariae was 23.4% (95% CI: 23.4–30.8), whereas Ov16 seroprevalence was 53.2% (95% CI: 47.9–58.4). A moderate positive percentage agreement (50.4%) and a high negative percentage agreement (69.2%) was found between skin snip and Ov16 serology in the whole population, while in children aged <10 years, the agreements were higher (positive percentage agreement: 62.6%; negative percentage agreement: 83.5%). In addition, no associations were found between ivermectin intake, Mf counts and estimated IgG4 concentration of participants. Anti-Ov16 IgG4 were higher in individuals harboring microfilariae than their negative counterparts (p<0.0001), though a negative correlation was found between skin microfilarial counts and anti-Ov16 IgG4 levels (r = -0.2400; p = 0.03). No variation in microfilarial counts according to age and gender was observed. Though positively correlated with age (r = 0.4020; p<0.0001), IgG4 was significantly different between the different age classes (p<0.0001).Conclusion/SignificanceOur results revealed moderate positive and negative agreements between parasitological and immunological parameters of onchocerciasis infection after several rounds MDA. Anti-Ov16 IgG4 levels increased with age but decreased with microfilarial counts, suggesting a variation of anti-Ov16 IgG4 as a result of constant exposure and accumulation of infection. This brings evidence sustaining the use of Ov16 serology in children as evaluation tool. However, additional investigations are needed to further reshape the appropriate age range among children aged <10 years old.

High infection rates for onchocerciasis and soil-transmitted helminthiasis in children under five not receiving preventive chemotherapy: a bottleneck to elimination

BackgroundThe current mainstay for control/elimination of onchocerciasis and soil-transmitted helminthiasis (STH) relies on ivermectin- and mebendazole/albendazole-based preventive chemotherapies. However, children under five years of age have been excluded in both research activities and control programs, because they were believed to have insignificant infection rates. There is therefore a need for up-to-date knowledge on the prevalence and intensity of STH and onchocerciasis infections in this age group. This study aimed at assessing the rates and intensities of onchocerciasis and STH infections in children under five years of age who are excluded from ivermectin- or mebendazole/albendazole-based preventive chemotherapies.MethodsA series of cross-sectional surveys was conducted in four Health Districts in the Centre and Littoral Regions of Cameroon between 2018 and 2019. All subjects aged 2 to 4 years, were screened for prevalence (or infection rate) and intensity [number of eggs per gram of stool (epg) or number of microfilariae per skin snip (mf/ss)] of STH and onchocerciasis infections respectively using the Kato-Katz and skin snip methodologies. Chi-square and the non-parametric tests (Mann Whitney and Kruskal Wallis) were used to compare infection rates and intensities of infections between Health Districts and genders, respectively.ResultsA total of 421 children were enrolled in this study. The overall prevalence of onchocerciasis was 6.6% [95% confidence interval (CI): 4.3‒9.9], ranging from 3.6% (in the Ntui Health District) to 12.2% (in the Bafia Health District). The intensity of infection ranged from 0.5 to 46 microfilariae per skin snip [median: 5; interquartile range (IQR): 2.25‒8.5]. The overall prevalence of STH was 9.6% (95% CI: 6.5‒13.9), with a high infection rate (29.6%) in the Akonolinga Health District. Two STH species (Ascaris lumbricoides and Trichuris trichiura) were found among infected individuals. The median intensities of STH infections were 1,992 epg (IQR: 210‒28,704) and 96 epg (IQR: 48‒168) for A. lumbricoides and T. trichiura, respectively.ConclusionsThis study reveals that children < 5 years of age are highly infected with STH and onchocerciasis, and could contribute to the spread of these diseases, perpetuating a vicious circle of transmission and hampering elimination efforts. These findings reveal the urgent need to provide (or scale) treatments (likely pediatric formulations) to these preschool-aged children, especially in areas of high transmission, to accelerate efforts to reach WHO 2030 target.Graphical

Black flies and Onchocerciasis: Knowledge, attitude and practices among inhabitants of Alabameta, Osun State, Southwestern, Nigeria.

This study reports knowledge of residents of Alabameta community, Osun State, Nigeria on the bioecology and socio-economic burden of black flies and onchocerciasis. Using structured questionnaires and Focus Group Discussion (FGD), a total of 150 community respondents participated in the study. The knowledge of the residents on the existence of black flies in the community was significant (p<0.05) as all the 150 respondents confirmed the presence of black flies with the local name 'Amukuru' i.e causing itching. However, their lack of knowledge of the flies breeding site (104) (69%), prevention (134) (89%), cause (132) (88%), and treatment (133) (89%) of onchocerciasis was profound. Majority 147(98%) of the respondents reported that flies bite more in the wet season as against dry season 3(2%) and have a higher affinity (124) (82%) for biting the leg than any other part of the body. A larger percentage (89%) of the respondents are unaware of any medication for the treatment of onchocerciasis while 11% are aware. There had been no sensitization on onchocerciasis according to 89% of the respondents. Due to lack of resident's knowledge on black flies bioecology which may continuously expose them to the bite of the flies and ultimately infection, it is paramount that the Osun State government and the NTD implementing partner map out new public health education strategies during routine Mass Administration of Medicines with Ivermectin with a view to preventing onchocerciasis infection as well as man-vector contact.

Sero-prevalence of Human Onchocerciasis and Lymphatic Filariasis in Low-Endemic communities of Ogun State, Nigeria

This study reports the status of onchocerciasis and lymphatic filariasis (LF) in communities with low endemicity in Ogun-State, Nigeria. The Ov16/Wb123 biplex Rapid Diagnostic Test was used to screen 1,836 participants aged 5 years and above from 8 Local Government Areas (LGAs) from October to December, 2016. Skin snips and night blood were also used for microscopic detection of microfilariae (MF). A cumulative seroprevalence of 9.4% and 0.42% was recorded for onchocerciasis and LF respectively with a co-infection rate of 0.4%. Among the LGAs screened, Ijebu North-East recorded the highest seroprevalence of onchocerciasis (26.4%) and LF (0.9%) while Remo North, Sagamu and Obafemi-Owode LGAs recorded low prevalences ranging from 0.7 - 2.7% for both diseases. No positive result of MF was observed in all the communities screened, even in Ijebu North-East where seroprevalence was high, suggesting historic exposure to onchocerciasis and LF infection which may have occurred over time due to human migration during farming and fishing seasons. Extension of ongoing mass treatment in endemic LGAs is recommended for Ijebu North-East to ensure inclusion in the drive towards the elimination of the diseases in Ogun State.

Prevalence of Onchocerciasis Infection in the Sub-Saharan Africa Countries: A Systematic Review and Meta-analysis

International Journal of Medicine and Public Health,2021,11,4,170-178.DOI:10.5530/ijmedph.2021.4.32Published:September 2021Type:Review ArticlePrevalence of Onchocerciasis Infection in the Sub-Saharan Africa Countries: A Systematic Review and Meta-analysisMitiku Bonsa Debela, Dejene Hailu Kassa, and Taklu Marama Mokonnon Mitiku Bonsa Debela1,*, Dejene Hailu Kassa2, Taklu Marama Mokonnon3 1Department of Public Health, School of Medicine and Health Sciences, Madda Walabu University, ETHIOPIA. 2Schools of Public Health, College of Medicine and Health Sciences, Hawassa University, ETHIOPIA. 3Schools of Midwifery, College of Health Sciences and Medicine, Wolaita Sodo University, ETHIOPIA. Abstract:Background: Findings from many African countries show that the prevalence of onchocerciasis infection is fragmented and in a wide range. Clear and organized evidence that showed the prevalence is limited. Therefore, this systematic review and meta-analysis estimated the pooled prevalence of onchocerciasis infection in the sub-Saharan African Countries. Methods: Published articles found in Scopus, PubMed/Medline, Science Direct, Google Scholar, and Cochrane Library databases were systematically searched. Based on the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was employed to determine the prevalence for onchocerciasis infection among peoples of all age groups in Africa. Observational studies from 1 January 2015 to 10 February 2021 revealed the prevalence of onchocerciasis in the sub-Saharan African countries was incorporated. The pooled prevalence of the studies was computed using STATA version 14 statistical software. The heterogeneity of the study was assessed using Cochrane Q test statistics, the I-squared values test, and the Galbraith plot. Considering within and between variability, the randomeffect model was used to determine the pooled prevalence. Funnel plot and egger’s tests were conducted to assess publication bias. Results: Out of 1985 accessed studies, 17 studies fulfilled the eligibility criteria and were included to estimate the pooled prevalence of onchocerciasis infection. The pooled prevalence of onchocerciasis was 30% (95% CI: 13, 47) in sub-Saharan Africa. Thirty-two percent (95% CI: 9, 56)) and 28% (95% CI: 2, 54) of onchocerciasis infection were identified from the study conducted before 2015 and after 2015, respectively, based on the subgroup analysis. The prevalence of onchocerciasis among farmers and housewives was 35% (95% CI: 12, 58), 18% (95% CI: 10, 27), respectively. Conclusion: Onchocerciasis is still of immense public health importance. Hence, the local government and other stakeholders should implement rigorous and comprehensive onchocerciasis prevention strategies such as improved sanitation, vector control, mass drug administration campaigns, and multifaceted methods based on their context. Keywords:Africa, Meta-analysis, Onchocerciasis, Prevalence, Systematic reviewView:PDF (1.99 MB)

Onchocerciasis Fingerprints in the Geriatric Population: Does Host Immunity Play a Role?

One of the most debilitating consequences of aging is the progressive decline in immune function, known as immunosenescence. This phenomenon is characterized by a shift in T-cell phenotypes, with a manifest decrease of naive T-cells—dealing with newly encountered antigens—and a concomitant accumulation of senescent and regulatory T-cells, leading to a greater risk of morbidity and mortality in older subjects. Additionally, with aging, several studies have unequivocally revealed an increase in the prevalence of onchocerciasis infection. Most lymphatic complications, skin and eye lesions due to onchocerciasis are more frequent among the elderly population. While the reasons for increased susceptibility to onchocerciasis with age are likely to be multi-factorial, age-associated immune dysfunction could play a key role in the onset and progression of the disease. On the other hand, there is a growing consensus that infection with onchocerciasis may evoke deleterious effects on the host’s immunity and exacerbate immune dysfunction. Indeed, Onchocerca volvulus has been reported to counteract the immune responses of the host through molecular mimicry by impairing T-cell activation and interfering with the processing of antigens. Moreover, reports indicate impaired cellular and humoral immune responses even to non-parasite antigens in onchocerciasis patients. This diminished protective response may intensify the immunosenescence outcomes, with a consequent vulnerability of those affected to additional diseases. Taken together, this review is aimed at contributing to a better understanding of the immunological and potential pathological mechanisms of onchocerciasis in the older population.

Exploring Onchocerca volvulus Cysteine Protease Inhibitor for Multi-epitope Subunit Vaccine Against Onchocerciasis: An Immunoinformatics Approach

Onchocerciasis, caused by Onchocerca volvulus, affects more than 37 million people worldwide. Despite the progress achieved with mass drug distribution, suitable vaccines against onchocerciasis are needed to effectively eliminate the infection. The O. volvulus cysteine protease inhibitor (onchocystatin) is an immuno-dominant antigen detected in O. volvulus infections, capable of inducing protective immunity. Here, we explore the onchocystatin for a multi-epitope subunit vaccine candidate targeted against onchocerciasis. A multi-epitope vaccine candidate composed of RS-09 as adjuvant, a CD8+ T cell peptide, a CD4+ T cell peptide and a B cell peptide concatenated with suitable linkers was computationally constructed. Immune simulation of the vaccine response predicted several aspects of antibody-dependent and cellular-mediated immunity with accompanied B cell and helper T cell immune memory development. The levels of lFN-γ and IL-2 were also predicted to be elevated. Collectively, our results suggest that the multi-epitope vaccine construct has the potential to mimic the natural immunity targeted against onchocerciasis and other related filarial infections, and should be considered for further experimental validations.

Progress towards onchocerciasis elimination in Côte d'Ivoire: A geospatial modelling study.

BackgroundCôte d’Ivoire has had 45 years of intervention for onchocerciasis by vector control (from 1975 to 1991), ivermectin mass drug administration (MDA) (from 1992 to 1994) and community directed treatment with ivermectin (CDTi) from 1995 to the present. We modeled onchocerciasis endemicity during two time periods that correspond to the scale up of vector control and ivermectin distribution, respectively. This analysis illustrates progress towards elimination during these periods, and it has identified potential hotspots areas that are at risk for ongoing transmission.Methods and findingsThe analysis used Ministry of Health skin snip microfilaria (MF) prevalence and intensity data collected between 1975 and 2016. Socio-demographic and environmental factors were incorporated into a predictive, machine learning algorithm to create continuous maps of onchocerciasis endemicity. Overall predicted mean MF prevalence decreased from 51.8% circa 1991 to 3.9% circa 2016. The model predicted infection foci with higher prevalence in the southern region of the country. Predicted mean community MF load (CMFL) decreased from 10.1MF/snip circa 1991 to 0.1MF/snip circa 2016. Again, the model predicts foci with higher Mf densities in the southern region. For assessing model performance, the root mean squared error and R2 values were 1.14 and 0.62 respectively for a model trained with data collected prior to 1991, and 1.28 and 0.57 for the model trained with infection survey data collected later, after the introduction of ivermectin. Finally, our models show that proximity to permanent inland bodies of water and altitude were the most informative variables that correlated with onchocerciasis endemicity.Conclusion/SignificanceThis study further documents the significant reduction of onchocerciasis infection following widespread use of ivermectin for onchocerciasis control in Côte d’Ivoire. Maps produced predict areas at risk for ongoing infection and transmission. Onchocerciasis might be eliminated in Côte d’Ivoire in the future with a combination of sustained CDTi with high coverage, active surveillance, and close monitoring for persistent infection in previously hyper-endemic areas.

English

Despite the multitude of studies which have shown the use of medicinal plants in the management of parasitic diseases, little data was available on the plants used against onchocerciasis. Ethnobotanical surveys were carried out among traditional healers in the Far North region of Cameroon. Studies were conducted from July 2017 to May 2018 through direct interviews using a semi-structured questionnaire taking into consideration the socio-demographic characteristics of the respondents as well as their knowledge in the art of onchocerciasis and parasitic infections treatment using plant recipes. A total of one hundred people were interviewed in villages found in the Far North region of Cameroon: 43 were females and 57 males, among which, 71 were recognized as traditional healers. Adults were the most represented (71 respondents). The study identified 96 plant species belonging to 49 genera divided into 29 families among which the most represented was the Fabaceae (20 quotes). The most represented biotope was savannah (98%) and trees (51) were the most used followed by shrub (41). The leaves (40) are the organs which are mostly demanded and the main preparation method is a decoction (69) and 36 diseases and / or symptoms related to onchocerciasis and helminthiases were recorded. The medicinal plants identified, constitute an undeniable asset and a good database for the biological screening of plant-based antiparasitic molecules, which can lead to the manufacture of improved traditional medicines. Key words: Onchocerciasis, medicinal plants, ethnobotanical surveys, filariasis, Cameroon.

Transmission dynamics of onchocerciasis with two classes of infection and saturated treatment function

A mathematical model describing the epidemic interactions between humans and blackflies in the transmission of onchocerciasis is considered. In this model, the onchocerciasis infected human individuals are divided into two classes of infected humans with high and low microfilarial output incorporating saturated treatment function, which caters for high saturation of onchocerciasis disease. We analyze the model feasible region and obtain the basic reproduction number [Formula: see text] using the next generation matrix method. Also, we obtain the onchocerciasis-free and onchocerciasis endemic equilibrium solutions and show that if [Formula: see text] is less than unity, the onchocerciasis-free equilibrium is locally and globally asymptotically stable. Furthermore, we employed a Lyapunov function to analyze the global asymptotic stability of the onchocerciasis — endemic equilibrium whenever [Formula: see text] is greater than unity. In addition, data on mass drug distribution of ivermectin drug to combat onchocerciasis prevalence in Ekiti state of Nigeria were fitted to the model. Graphical results reveal that consistent annual or bi-annual distribution of ivermectin drug in the region is effective in reducing the disease menace. Further simulations also show that public health control measures are needed to minimize infectious contact between humans and blackflies which leads to onchocerciasis infections and visual blindness.

On the existence of invariant domain and local asymptotic behavior of a delayed onchocerciasis model

In this paper, a mathematical model describing the transmission dynamics of onchocerciasis with distributed delays in infection incubation and recovery in humans and blackfly host population is formulated. We showed that the delayed model is positively invariant and bounded. Also, we obtain the onchocerciasis-free and endemic steady-state solutions as well as the basic reproduction number [Formula: see text] of the delayed onchocerciasis model. We found that the delayed onchocerciasis model is locally asymptotically stable whenever [Formula: see text]. The findings suggest that, for [Formula: see text] to be less than unity, effective use of ivermectin drug for treatment, distribution of treated nets and cloths, etc., is necessary for the minimization and possible elimination of onchocerciasis infection.

Implementation of test-and-treat with doxycycline and temephos ground larviciding as alternative strategies for accelerating onchocerciasis elimination in an area of loiasis co-endemicity: the COUNTDOWN consortium multi-disciplinary study protocol

BackgroundOnchocerciasis is a priority neglected tropical disease targeted for elimination by 2025. The standard strategy to combat onchocerciasis is annual Community-Directed Treatment with ivermectin (CDTi). Yet, high prevalence rates and transmission persist following > 12 rounds in South-West Cameroon. Challenges include programme coverage, adherence to, and acceptability of ivermectin in an area of Loa loa co-endemicity. Loiasis patients harbouring heavy infections are at risk of potentially fatal serious adverse events following CDTi. Alternative strategies are therefore needed to achieve onchocerciasis elimination where CDTi effectiveness is suboptimal.Methods/designWe designed an implementation study to evaluate integrating World Health Organisation-endorsed alternative strategies for the elimination of onchocerciasis, namely test-and-treat with the macrofilaricide, doxycycline (TTd), and ground larviciding for suppression of blackfly vectors with the organophosphate temephos. A community-based controlled before-after intervention study will be conducted among > 2000 participants in 20 intervention (Meme River Basin) and 10 control (Indian River Basin) communities. The primary outcome measure is O. volvulus prevalence at follow-up 18-months post-treatment. The study involves four inter-disciplinary components: parasitology, entomology, applied social sciences and health economics. Onchocerciasis skin infection will be diagnosed by skin biopsy and Loa loa infection will be diagnosed by parasitological examination of finger-prick blood samples. A simultaneous clinical skin disease assessment will be made. Eligible skin-snip-positive individuals will be offered directly-observed treatment for 5 weeks with 100 mg/day doxycycline. Transmission assessments of onchocerciasis in the communities will be collected post-human landing catch of the local biting blackfly vector prior to ground larviciding with temephos every week (0.3 l/m3) until biting rate falls below 5/person/day. Qualitative research, including in-depth interviews and focus-group discussions will be used to assess acceptability and feasibility of the implemented alternative strategies among intervention recipients and providers. Health economics will assess the cost-effectiveness of the implemented interventions.ConclusionsUsing a multidisciplinary approach, we aim to assess the effectiveness of TTd, alone or in combination with ground larviciding, following a single intervention round and scrutinise the acceptability and feasibility of implementing at scale in similar hotspots of onchocerciasis infection, to accelerate onchocerciasis elimination.