Direct Proteomic Detection and Prioritization of 19 Onchocerciasis Biomarker Candidates in Humans.

Onchocerca volvulus, the causative agent of onchocerciasis, infects over 20 million people and can cause severe dermatitis and ocular conditions including blindness. Current treatments employed in mass drug administration programs do not kill adult female worms, and common diagnostic tests cannot reliably assess viability of adult worms. There is an urgent need for better diagnostic tests to facilitate monitoring the efficacy of new treatments and disease elimination efforts. Here, eight plasma samples collected from individuals infected with O. volvulus and seven from uninfected individuals were analyzed by MS/MS spectrometry to directly identify O. volvulus proteins present in infected but absent in uninfected control samples. This direct proteomic approach for biomarker discovery had not been previously employed for onchocerciasis. Among all detected proteins, 19 biomarker candidates were supported by two or more unique peptides, identified in the plasma of at least three O. volvulus-infected human samples and absent in all control samples. Comprehensive analysis and ranking of these candidates included detailed functional annotation and a review of RNA-seq gene expression profiles. Isotope-labeled standard peptides were run in parallel and validated MS/MS peptide identifications for 15 peptides from 11 of the 19 proteins, and two infected urine and one uninfected urine sample was used for additional validation. A major antigen/OVOC11613 was identified as the most promising candidate with eight unique peptides across five plasma samples and one urine sample. Additional strong candidates included OVOC1523/ATP synthase, OVOC247/laminin and OVOC11626/PLK5, and along with OVOC11613, and were also detected in urine samples from onchocerciasis patients. This study has identified a promising novel set of proteins that will be carried forward to develop assays that can be used for diagnosis of O. volvulus infections and for monitoring treatment efficacy.

An Updated Economic Assessment of Moxidectin Treatment Strategies for Onchocerciasis Elimination.

BACKGROUND: Concerns that annual mass administration of ivermectin, the predominant strategy for onchocerciasis control and elimination, may not lead to elimination of parasite transmission (EoT) in all endemic areas have increased interest in alternative treatment strategies. One such strategy is moxidectin. We performed an updated economic assessment of moxidectin- relative to ivermectin-based strategies. METHODS: We investigated annual and biannual community-directed treatment with ivermectin (aCDTI, bCDTI) and moxidectin (aCDTM, bCDTM) with minimal or enhanced coverage (65% or 80% of total population taking the drug, respectively) in intervention-naive areas with 30%, 50%, or 70% microfilarial baseline prevalence (representative of hypo-, meso-, and hyperendemic areas). We compared programmatic delivery costs for the number of treatments achieving 90% probability of EoT (EoT90), calculated with the individual-based stochastic transmission model EPIONCHO-IBM. We used the costs for 40 years of program delivery when EoT90 was not reached earlier. The delivery costs do not include drug costs. RESULTS: aCDTM and bCDTM achieved EoT90 with lower programmatic delivery costs than aCDTI with 1 exception: aCDTM with minimal coverage did not achieve EoT90 in hyperendemic areas within 40 years. With minimal coverage, bCDTI delivery costs as much or more than aCDTM and bCDTM. With enhanced coverage, programmatic delivery costs for aCDTM and bCDTM were lower than for aCDTI and bCDTI. CONCLUSIONS: Moxidectin-based strategies could accelerate progress toward EoT and reduce programmatic delivery costs compared with ivermectin-based strategies. The costs of moxidectin to national programs are needed to quantify whether delivery cost reductions will translate into overall program cost reduction.

Synthesizing environmental, epidemiological and vector and parasite genetic data to assist decision making for disease elimination.

We present a framework for identifying when conditions are favourable for transmission of vector-borne diseases between communities by incorporating predicted disease prevalence mapping with landscape analysis of sociological, environmental and host/parasite genetic data. We explored the relationship between environmental features and gene flow of a filarial parasite of humans, Onchocerca volvulus, and its vector, blackflies in the genus Simulium. We generated a baseline microfilarial prevalence map from point estimates from 47 locations in the ecological transition separating the savannah and forest in Ghana, where transmission of O. volvulus persists despite onchocerciasis control efforts. We generated movement suitability maps based on environmental correlates with mitochondrial population structure of 164 parasites from 15 communities and 93 vectors from only four sampling sites, and compared these to the baseline prevalence map. Parasite genetic distance between sampling locations was significantly associated with elevation (r = .793, p = .005) and soil moisture (r = .507, p = .002), while vector genetic distance was associated with soil moisture (r = .788, p = .0417) and precipitation (r = .835, p = .0417). The correlation between baseline prevalence and parasite resistance surface maps was stronger than that between prevalence and vector resistance surface maps. The centre of the study area had high prevalence and suitability for parasite and vector gene flow, potentially contributing to persistent transmission and suggesting the importance of re-evaluating transmission zone boundaries. With suitably dense sampling, this framework can help delineate transmission zones for onchocerciasis and would be translatable to other vector-borne diseases.

Association of haemato-biochemical indices and blood composite ratios with microfilaridermia in Onchocerciasis patients.

BACKGROUND: Onchocerciasis causes chronic systemic inflammation. Several studies have used markers such as haemato-biochemical indices to predict the occurrence of systemic inflammation. This study assessed the variability and predictability of haemato-biochemical indices and blood composite ratios (BCRs) in microfilariae positive (MF+) and microfilariae negative (MF-) subgroups of onchocercomata participants. METHODS: One hundred and five (105) MF + and 34 MF- participants were retrospectively recruited into the study. Screening for the presence of O. volvulus microfilariae was done from skin snips taken from the left and right iliac crests of participants using established and approved protocols. Haematological and biochemical indices were measured using standard laboratory automated analyzers. Blood composite ratios (BCRs) were calculated as ratios of the absolute parameters involved. RESULTS: A significantly increased total WBC, absolute eosinophil, eosinophil percent and absolute basophil were observed in the MF + participants compared to MF- participants. Reduced gamma-glutamyl transferase (GGT) with increased estimated glomerular filtration rate (eGFR) was significantly associated with MF + participants compared to MF- participants. BCRs were significantly higher for eosinophil-to-neutrophil ratio (ENR), eosinophil-to-monocyte ratio (EMR), eosinophil-to-basophil ratio (EBR) and eosinophil-to-lymphocyte ratio (ELR) in MF + participants compared to MF- participants. After multivariate adjustment, onchocercomata participants with increased eosinophil counts (aOR = 13.86, 95% CI [2.07-92.90], p = 0.007), ENR x10 (aOR = 1.42, 95% CI [1.05-1.93], p = 0.025), EMR (aOR = 2.64, 95% CI [1.25-5.60], p = 0.011), EBR (aOR = 1.07, 95% CI [1.01-1.10], p = 0.020) and ELR x10 (aOR = 1.69, 95% CI [1.14-2.51], p = 0.009) were more likely to have microfilaridermia. CONCLUSIONS: Elevated eosinophil counts with higher ENR, EMR, EBR and ELR levels are significantly associated with microfilaridermia in onchocercomata participants. Combining BCRs with eosinophil count significantly led to an improvement in the conventional model for predicting microfilaridermia.

The spectrum of disease and tau pathology of nodding syndrome in Uganda.

Nodding syndrome is an enigmatic recurrent epidemic neurologic disease that affects children in East Africa. The illness begins with vertical nodding of the head and can progress to grand mal seizures and death after several years. The most recent outbreak of nodding syndrome occurred in northern Uganda. We now describe the clinicopathologic spectrum of nodding syndrome in northern Uganda. The neuropathologic findings of 16 children or young adults with fatal nodding syndrome were correlated with the onset, duration and progression of their neurological illness. The affected individuals ranged in age from 14 to 25 years at the time of death with a duration of illness ranging from 6-15 years. All 16 cases had chronic seizures. In 10 cases, detailed clinical histories were available and showed that three individuals had a clinical course that was predominantly characterized by epilepsy, whereas the other seven individuals had progressive cognitive, behavioural and motor decline, in addition to epilepsy. The main neuropathologic findings included: tau pathology (16/16 cases), cerebellar degeneration (11/16 cases) and white matter degeneration (7/16 cases). The tau pathology was characterized by filamentous tau-positive deposits in the form of neurofibrillary tangles, pre-tangles and dot-like grains and threads in the neuropil. All cases showed some degree of tau pathology in the neocortex and in the locus coeruleus with frequent involvement of the substantia nigra and tegmental nuclei and lesser involvement of other grey matter sites, but there was a lack of glial tau pathology. The tau pathology in the neocortex showed a multifocal superficial laminar pattern. We conclude that nodding syndrome is a clinicopathological entity associated consistently with tau pathology, but our observations did not establish the cause of the disease, or an explanation for the tau pathology.

Differential susceptibility of Onchocerca ochengi adult male worms to flubendazole in gerbils and hamsters.

Onchocerciasis is a devastating skin and eye disease that afflicts about 21 million people, most of whom live in sub-Saharan Africa. Its control with the microfilaricidal drug ivermectin is limited, thus necessitating the development of preclinical animal models to aid in the discovery of a macrofilaricide. Previously, we found that Onchocerca ochengi (the closest relative of the human O. volvulus) worm masses survive better in hamsters than in gerbils. The aim of this study was to compare the survival of O. ochengi adult male worms and their susceptibility to flubendazole (FBZ, a macrofilaricide) in gerbils and hamsters. The animals were intraperitoneally implanted with O. ochengi male worms, treated with FBZ, and sacrificed 35 days post-implantation. Unlike gerbils which had some worms moving freely in the peritoneum and some in newly formed nodules (neo-nodules), all the worms in the hamsters were found in neo-nodules. FBZ significantly decreased worm burden, motility, and viability in gerbils whereas it had no significant effect in hamsters. These results highlight a major difference in how O. ochengi adult male worms are sustained and affected by FBZ in gerbils compared to hamsters. Understanding the difference between these two models is important in the development of effective macrofilaricides for onchocerciasis.

Persistence of onchocerciasis and associated dermatologic and ophthalmic pathologies after 27 years of ivermectin mass drug administration in the middle belt of Ghana.

OBJECTIVES: There is a pressing need to regularly evaluate the progress of onchocerciasis elimination programmes to timely identify and mitigate potential risks hindering the reaching of the 2030 targets proposed by the World Health Organization (WHO) in its roadmap on neglected tropical diseases (NTDs). We determined the prevalence of onchocerciasis and associated dermatological and ophthalmological manifestations in six endemic communities in the Bono Region of Ghana after 27 years of ivermectin mass treatment. METHODS: In a cross-sectional study, 564 participants aged ≥5 years were enrolled (49.1% females), with a median age of 26 (range: 5-89) years. In 54% and 47%, skin-snip microscopy and Ov16 rapid diagnostic tests were performed, respectively. Skin disease was determined using the WHO Skin NTD App. Visual function assessments included tests of visual acuity. RESULTS: The overall microfilarial prevalence was 12.5% (38/305) and Ov16 seroprevalence was 24.2% (64/265). Severe itching was recorded in 24.3%, acute papular onchodermatitis in 52.8%, chronic papular onchodermatitis in 12.5%, lichenified onchodermatitis in 0.7%, skin atrophy in 11.3%, depigmentation in 1.7% and palpable nodules in 5.3%. Of the 301 persons in which visual acuity was examined, 17% were visually impaired and 5.3% were blind and 47.3% presented with cataract. Chronic papular onchodermatitis, lichenified onchodermatitis, depigmentation and visual impairment were significantly associated with the presence of skin microfilariae and Ov16 seropositivity. CONCLUSIONS: The persistence of Onchocerca volvulus infection and onchocerciasis-associated dermatological and ophthalmological pathologies after prolonged treatment is of concern. There is a need to include morbidity management in onchocerciasis elimination programmes and understand better patterns of treatment coverage, adherence and actual intake of ivermectin.

Is the antiparasitic drug ivermectin a suitable candidate for the treatment of epilepsy?

There are only a few drugs that can seriously lay claim to the title of "wonder drug," and ivermectin, the world's first endectocide and forerunner of a completely new class of antiparasitic agents, is among them. Ivermectin, a mixture of two macrolytic lactone derivatives (avermectin B1a and B1b in a ratio of 80:20), exerts its highly potent antiparasitic effect by activating the glutamate-gated chloride channel, which is absent in vertebrate species. However, in mammals, ivermectin activates several other Cys-loop receptors, including the inhibitory γ-aminobutyric acid type A and glycine receptors and the excitatory nicotinic acetylcholine receptor of brain neurons. Based on these effects on vertebrate receptors, ivermectin has recently been proposed to constitute a multifaceted wonder drug for various novel neurological indications, including alcohol use disorders, motor neuron diseases, and epilepsy. This review critically discusses the preclinical and clinical evidence of antiseizure effects of ivermectin and provides several arguments supporting that ivermectin is not a suitable candidate drug for the treatment of epilepsy. First, ivermectin penetrates the mammalian brain poorly, so it does not exert any pharmacological effects via mammalian ligand-gated ion channels in the brain unless it is used at high, potentially toxic doses or the blood-brain barrier is functionally impaired. Second, ivermectin is not selective but activates numerous inhibitory and excitatory receptors. Third, the preclinical evidence for antiseizure effects of ivermectin is equivocal, and at least in part, median effective doses in seizure models are in the range of the median lethal dose. Fourth, the only robust clinical evidence of antiseizure effects stems from the treatment of patients with onchocerciasis, in which the reduction of seizures is due to a reduction in microfilaria densities but not a direct antiseizure effect of ivermectin. We hope that this critical analysis of available data will avert the unjustified hype associated with the recent use of ivermectin to control COVID-19 from recurring in neurological diseases such as epilepsy.

Non-adherence to ivermectin in onchocerciasis-endemic communities with persistent infection in the Bono Region of Ghana: a mixed-methods study.

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

Disability assessment among persons with epilepsy in Mahenge, an onchocerciasis-endemic area in Tanzania: A cross-sectional study.

BACKGROUND: A high prevalence of epilepsy has been observed in the onchocerciasis-endemic focus of Mahenge, Tanzania. This study sought to assess the degree of disability experienced by persons with epilepsy (PWE) in Mahenge and identify associations with sociodemographic and clinical features. METHOD: This cross-sectional study was conducted in Mahenge, Tanzania, between February and July 2020. PWE were recruited from the Mahenge epilepsy clinic and four neighbouring rural villages (Mdindo, Mzogezi, Mzelezi and Sali). Data were collected using the 36-item version of the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) questionnaire for adults. For children aged 5-17 years, we used the Module on Child Functioning developed by UNICEF and the Washington Group. Questionnaires were administered by trained research assistants. Descriptive statistics were performed, and multivariable analyses (gamma and logistic regressions) were conducted. RESULTS: A total of 321 adults (45.5% males) and 48 children (55.3% males) with epilepsy participated. The overall median WHODAS 2.0 score was 4.8% (IQR: 0.9-18.9). The most affected disability domain was 'participating in the society' (median score: 12.5%, IQR: 0-29.2). Fifteen (31.3%) of the children with epilepsy had a disability in at least one domain of the child functioning module, with the 'accepting change' domain harbouring the highest proportion of disabled children (12.5%). Higher seizure frequency and longer epilepsy duration were associated with more disability. CONCLUSION: PWE in Mahenge experience variable degrees of disability. The affected domains indicate the need for societal rehabilitation of PWE in various community and/or social activities. Peer-support groups were instituted at the study sites to address these needs.

Quality of life of persons with epilepsy in Mahenge, an onchocerciasis-endemic area in Tanzania: A cross-sectional study.

OBJECTIVE: This study investigated the quality of life (QoL) of adults with epilepsy living in Mahenge, an onchocerciasis-endemic area in Tanzania with a high prevalence of onchocerciasis-associated epilepsy (OAE). METHODS: Between February and December 2020, persons with epilepsy (PWE) were recruited from four rural villages in Mahenge: Mdindo, Msogezi, Mzelezi, and Sali. For PWE who could not answer the questionnaire due to their mental or physical disability, a family member was asked to answer the questions instead. The Quality of Life in Epilepsy Inventory-31 (QOLIE-31) questionnaire used contained seven domains. The raw domain scores were transformed to 0-100% subscales, with higher scores indicating better QoL. The global QoL was calculated from the subscales using the overall QOLIE-31 score formula. RESULTS: In total, 96 PWE were enrolled in the study with a median age of 28 (range: 18-60) years, of whom 45 (47%) were male. The questionnaires were answered by PWE (54.8%) or one of their family members (45.2%). Most PWE were single (81%), and half never attended school. About two-thirds (65%) of PWE were suspected of having OAE, and a third (31%) had a history of head nodding seizures. Most PWE were treated with phenobarbital (85.4%) and had high treatment adherence (96.9%). Still, the number of seizures per week ranged from 0 to 7, with a median of one. The mean global QOLIE-31 score was 66.9 (range: 38.3-92.1) out of 100.0. Predictors of lower QoL were living in Sali Village and experiencing seizures the week before the interview. In contrast, completing primary school and switching to second-line anti-seizure medication were predictors of higher QoL. CONCLUSION: In order to improve the QoL of PWE in Mahenge, it is vital to optimize anti-seizure medication regimens to decrease the frequency of seizures and to increase the schooling of PWE.

Epidemiology of epilepsy and relationship with onchocerciasis prevalence in villages of the Ntui Health District of Cameroon.

BACKGROUND: A strong association between epilepsy and onchocerciasis endemicity has been reported. We sought to document the epidemiology of epilepsy in onchocerciasis-endemic villages of the Ntui Health District in Cameroon and investigate how this relates to the prevalence of onchocerciasis. METHODS: In March 2022, door-to-door epilepsy surveys were conducted in four villages (Essougli, Nachtigal, Ndjame, and Ndowe). Ivermectin intake during the 2021 session of community-directed treatment with ivermectin (CDTI) was investigated in all participating village residents. Persons with epilepsy (PWE) were identified through a two-step approach: administration of a 5-item epilepsy screening questionnaire followed by clinical confirmation by a neurologist. Epilepsy findings were analyzed together with onchocerciasis epidemiological data previously obtained in the study villages. RESULTS: We surveyed 1663 persons in the four study villages. The 2021 CDTI coverage for all study sites was 50.9%. Overall, 67 PWE were identified (prevalence of 4.0% (IQR: 3.2-5.1) with one new-onset case during the past 12 months (annual incidence of 60.1 per 100,000 persons). The median age of PWE was 32 years (IQR: 25-40), with 41 (61.2%) being females. The majority (78.3%) of PWE met the previously published criteria for onchocerciasis-associated epilepsy (OAE). Persons with a history of nodding seizures were found in all villages and represented 19.4% of the 67 PWE. Epilepsy prevalence was positively correlated with onchocerciasis prevalence (Spearman Rho = 0.949, p = 0.051). Meanwhile, an inverse relationship was observed between distance from the Sanaga river (blackfly breeding site) and the prevalence of both epilepsy and onchocerciasis. CONCLUSION: The high epilepsy prevalence in Ntui appears to be driven by onchocerciasis. It is likely that decades of CDTI have likely contributed to a gradual decrease in epilepsy incidence, as only one new case occurred in the past year. Therefore, more effective elimination measures are urgently needed in such endemic areas to curb the OAE burden.

Disease perception, impacts and coping strategies for onchocerciasis in Southeast Nigeria: a qualitative study among patients and program managers.

BACKGROUND: Onchocerciasis is a disease of public health concern due to the devastating consequences of the disease which impacts negatively on the lives of the people. The negative impact of the disease may affect its perception and lead to the adoption of some coping strategies. Therefore, understanding the disease perception, impacts and coping strategies used by onchocerciasis patients will help plan health interventions aimed at improving their general well-being. METHODS: This was a community-based study that employed a qualitative method through Key informant interviews (KII) with program managers and focus group discussions (FGD) among people who had Onchocerciasis. Four sessions of FGDs with a total of thirty-two (32) participants and eleven KIIs were conducted to ascertain their in-depth experience in five thematic areas. RESULTS: In these communities, onchocerciasis is perceived to have been caused mainly by the bite of blackflies. Other presumed causes by the patients included drinking polluted water, poor environmental sanitation and witchcraft. The disease had a significant detrimental influence on both the physical and financial aspects of life with limited emotional and social impacts. The long-term clinical manifestations of onchocerciasis triggered pain and insufficient mobility. Thus, onchocerciasis patients experienced impairment in normal daily life activities (farming, etc.), dependency, depression and inability to participate in social events. These manifestations stimulated various coping strategies, mainly, nodulectomy by traditional healers. Others included self-medication, taking an overdose of ivermectin, and the use of alcohol. CONCLUSION: Misconceptions about the cause of onchocerciasis still exist among people with the disease. The consequences of the disease impact negatively on various aspects of their lives and stimulate various coping strategies. Therefore, health promotion messages to the public should aim at dispelling misconceptions about the disease and promote healthy coping strategies.

Coverage of preventive measures and surveillance for neglected tropical diseases in hard-to-reach communities in Ghana.

BACKGROUND: Neglected tropical diseases (NTDs) are a major public health burden which mainly affects poor populations living in tropical environments and hard-to-reach areas. The study sought to examine coverage of preventive efforts, and case surveillance for NTDs in hard-to-reach communities in Ghana. METHODS: The study investigated treatment efforts for lymphatic filariasis (LF), and onchocerciasis and schistosomiasis/soil transmitted helminths (SCH/STH) at household level, in difficult-to-access communities in Ghana. A total of 621 households were sampled from 6 communities in the Western, Oti and Greater Accra regions. RESULTS: Over 95% of the households surveyed were covered under mass drug administration (MDA) campaigns for lymphatic filariasis (LF) and onchocerciasis. More than 80% of households had received at least two visits by community drug distributors under the MDA campaigns in the last two years preceding the study. In addition, over 90% of households in the LF and onchocerciasis endemic communities had at least one member using anthelminthic medications under the MDA campaigns in the 12 months preceding the study. However, households where no member had taken anthelminthic medications in 12 months preceding the study were over 6 times likely to have someone in the household with LF. CONCLUSIONS: This study determined that SCH/STH, LF and onchocerciasis are of serious public health concern in some communities in Ghana. There is an urgent need for holistic practical disease control plan involving both financial and community support to ensure total control of NTDs in difficult-to-access communities is achieved.

Survival of worm masses of Onchocerca ochengi in gerbils and hamsters: implications for the development of an in vivo macrofilaricide screening model.

Onchocerciasis, the second leading infectious cause of blindness, afflicts approximately 21 million people globally. Its control is limited to the use of the microfilaricidal drugs, ivermectin and moxidectin. Both drugs are unable to kill the adult worms which can survive for up to 15 years in patients, justifying the urgent need for potent and novel macrofilaricides that kill adult worms. The development of such drugs has been hindered by the lack of an appropriate small laboratory animal model to evaluate potential drug candidates in vivo. This study assessed the survival of O. ochengi female worms and their embryos over time in two laboratory rodents: gerbils and hamsters and tested using "proof-of-concept" studies, whether known macrofilaricidal drugs can kill these worms. Animals were surgically implanted with mechanical or collagenase-liberated O. ochengi worm masses, and necropsied at various time points to test for survival. Recovered worm masses were assessed for viability by biochemical analysis (MTT/formazan assay) or fecundity (embryogram). Flubendazole (FBZ) administered at 20 mg/kg body weight was used to validate both rodent models. By day 26 post-implantation of 15 worm masses, a median of 7.00 (4.00-10.00) was recovered from hamsters, and 2.50 (2.00-4.00) from gerbils. Worm masses recovered from gerbils were mostly disintegrated or fragmented, with significantly higher fragmentation observed with collagenase-liberated worm masses. FBZ had no significant effect on the number of worm masses recovered, but enhanced embryo degradation in gerbils and reduced worm mass viability in hamsters. This exploratory study has revealed the gerbil and hamster as permissible rodents to adult female worms of O. ochengi. The hamsters appeared to maintain the worms longer, compared to gerbils.

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

BACKGROUND: Onchocerciasis 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. METHODS: A 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. RESULTS: As 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. CONCLUSIONS: Our 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.

Persistence of onchocerciasis in villages in Enugu and Ogun states in Nigeria following many rounds of mass distribution of ivermectin.

BACKGROUND: Onchocerciasis is endemic in most local government areas (LGAs) in Enugu and Ogun states. Most meso- and hyper-endemic LGAs have received many rounds of ivermectin mass drug administration (MDA). This study aimed to determine the current prevalence of onchocerciasis in villages in Enugu and Ogun states that were formerly highly endemic and to assess progress toward elimination of the infection in areas believed to be at high risk for persistence. METHODS: Cross-sectional community surveys were conducted 8 to 12 months after the last round of MDA in 16 villages (6 in Enugu state and 10 in Ogun state) in individuals aged ≥ 18 years. Study participants were examined for the presence of palpable subcutaneous nodules. Skin snips from the posterior iliac crests were used to assess microfiladermia (Mf) prevalence and density. RESULTS: 643 subjects were palpated for nodules and 627 individuals (225 in Enugu state; 402 in Ogun state) provided skin snips. Nodule prevalence in the study villages ranged from 42 to 66.7% in Enugu state and from 0 to 25.0% in Ogun state. Mf prevalence in the Enugu and Ogun study villages ranged from 32 to 51.1% and 0 to 28.6%, respectively. Geometric mean skin Mf density in surveyed Enugu state villages ranged between 1 and 3.1 Mf/mg; these values were < 1 Mf/mg in all but one community in Ogun state villages. CONCLUSION: Results from this study show that onchocerciasis persists in adults in many villages in Enugu and Ogun states despite many prior rounds of ivermectin MDA. Prevalence was higher in villages surveyed in Enugu than in Ogun. Low Mf densities suggest the MDA program is working well to reduce disease, but more time will be required to reach the elimination goal.

Epileptogenesis in Common Parasitic Infections.

PURPOSE OF THE REVIEW: Neurocysticercosis (NCC) has been well recognized as a leading cause of epilepsy. More recently, studies of other parasitic diseases such as cerebral malaria (CM) and onchocerciasis are yielding novel insights into the pathogenesis of parasite-associated epilepsy. We compare the clinical and electrophysiological findings in epilepsy associated with these highly prevalent parasites and discuss the mechanisms involved in epileptogenesis. RECENT FINDINGS: Electrophysiological and imaging biomarkers continue to emerge, and individuals who are at-risk of developing parasite-associated epilepsies are being identified with greater reliability. While both Taenia solium and Plasmodium falciparum directly affect the brain parenchyma, Onchocerca volvulus is not known to invade the central nervous system. Thus, the causal association between O. volvulus and epilepsy remains controversial. Both NCC and CM have a well-defined acute phase when the parasites directly or indirectly invade the brain parenchyma and lead to local inflammatory changes. This is followed by a chronic phase marked by recurrent seizures. However, these stages of epileptogenic process have not been identified in the case of O. volvulus.

Community knowledge, attitudes, and practices regarding epilepsy in Mahenge, Tanzania: A socio-anthropological study in an onchocerciasis-endemic area with a high prevalence of epilepsy.

BACKGROUND: Throughout Africa, epilepsy is a highly stigmatized condition. It is often considered to be contagious. This study aimed to assess community knowledge, attitude, and practices toward epilepsy in four villages namely Mdindo, Msogezi, Mzelezi, and Sali within Mahenge division, in Morogoro region, Tanzania. These villages are located in an onchocerciasis-endemic area with a high prevalence of epilepsy. METHODS: A qualitative cross-sectional study was conducted between June and July 2019 within the framework of a multi-disciplinary research project investigating the association between onchocerciasis and epilepsy. Focus group discussions (FGDs) and in-depth interviews (IDIs) were held with persons with epilepsy (PWE) and their caretakers, community resource persons, and program coordinators of the neglected tropical diseases program. RESULTS: The main symptoms of epilepsy were well described by all participants in all villages. PWE and caretakers in all villages considered epilepsy to be a major health problem and some participants ranked it second in importance after malaria. The reported perceived causes of epilepsy included febrile seizures during childhood (locally known as degedege), heredity, evil spirits, and inhaling flatus or touching secretions from PWE, especially during seizures. Knowledge about the association between epilepsy and onchocerciasis was low. People with epilepsy are disregarded, stigmatized, and marginalized from various opportunities such as conjugal rights, schooling, leadership roles, and property inheritance. Traditional healers are often the first contact when seeking care after a person develops epilepsy. CONCLUSION: Epilepsy is a major health burden and public health concern in the Mahenge area. The negative attitudes toward PWE and misconceptions about the causes of epilepsy contribute to delays in seeking care at health facilities. Findings from this study will be used to optimize the comprehensive community-based epilepsy treatment program that was recently initiated in the area.

Prevalence of epilepsy in Ndom Health District (Littoral Region, Cameroon) after long-term ivermectin-based preventive chemotherapy for the control of onchocerciasis.

Assuming the causality relationship between Onchocerca volvulus infection and epilepsy onset, preventive chemotherapy for the control onchocerciasis can result to a significant impact on epilepsy burden. This study aimed at assessing the prevalence of epilepsy in an onchocerciasis endemic area under annual CDTI for 16 years. A cross-sectional survey was conducted in two communities (Kelleng and Nkonkwalla) located in the Ndom Health District (Littoral Region, Cameroon) to assess the prevalence of epilepsy using a standardized questionnaire for non-specialists in tropical areas. Data on the nuisance of onchocerciasis vector and distance of surveyed households to the river were also collected. Epilepsy status was collected from 367 participants (sex ratio (M/F): 1.13). The crude prevalence of epilepsy was estimated at 8.4 % (95 % CI: 5.8-11.8); the highest prevalence was found in females (13.8 %; 95 % CI: 8.8-20.3) compared to males (5.0 %; 95 % CI: 2.4-9.04)) (p-value = 0.02) and in Nkonkwalla (9.0 %; 95 % CI: 5.5-13.6) (p-value = 0.82) compared to Kelleng (7.7 %; 95 % CI: 4.06-13.13). After 16 years of CDTI in Kelleng, crude prevalence of epilepsy decreased from 10.2 % to 7.2 % (p-value = 0.19), whereas the age sex-standardized prevalence dropped from 13.5 % to 7.7 % between 2004 and 2020 (p-value = 0.05). The median age of epilepsy cases shifted from 24 (IQR: 20-30) in 2004 to 28 years (IQR: 23-34) in 2020. The shift in age-specific prevalence over the years suggests a decreasing incidence of epilepsy in areas under long-term CDTI and a significant impact of onchocerciasis control on the prevalence of epilepsy.