Onchocerca Volvulus Infection Research Articles

Genome-based tools for onchocerciasis elimination: utility of the mitochondrial genome for delineating Onchocerca volvulus transmission zones

National programs in Africa have expanded their objectives from control of onchocerciasis (river blindness) as a public health problem to elimination of parasite transmission, motivated by the reduction of Onchocerca volvulus infection prevalence in many African meso- and hyperendemic areas due to mass drug administration of ivermectin (MDAi). Given the large, contiguous hypo-, meso-, and hyperendemic areas, sustainable elimination of onchocerciasis in sub-Saharan Africa requires delineation of geographic boundaries for parasite transmission zones, so that programs can consider the risk of parasite re-introduction through vector or human migration from areas with ongoing transmission when making decisions to stop MDAi. We propose that transmission zone boundaries can be delineated by characterising the parasite genetic population structure within and between potential zones. We analysed whole mitochondrial genome sequences of 189 O. volvulus adults to determine the pattern of genetic similarity across three West African countries: Ghana, Mali, and Côte d’Ivoire. Population genetic structure indicates that parasites from villages near the Pru, Daka, and Black Volta rivers in central Ghana belong to one parasite population, indicating that the assumption that river basins constitute individual transmission zones is not supported by the data. Parasites from Mali and Côte d’Ivoire are genetically distinct from those from Ghana. This research provides the basis for developing tools for elimination programs to delineate transmission zones, to estimate the risk of parasite re-introduction via vector or human movement when intervention is stopped in one area while transmission is ongoing in others, to identify the origin of infections detected post-treatment cessation, and to investigate whether persisting prevalence despite ongoing interventions in one area is due to parasites imported from others.

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

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. 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. 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. 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.

Therapeutic Efficiency of Selected Ethnomedicinal Plants and Medications for Onchocerca volvulus Infection Endemic in Imo State, Southeastern Nigeria

Onchocerca volvulus infection – Onchocerciasis – is a priority tropical disease that has been targeted for elimination by World Health Organization (WHO). The Standard strategy to combat this chronic parasitic infection is the administration of Annual Community Directed Treatment with Ivermectin (CDTi), yet high prevalence rates and transmission persist. Alternative strategies are therefore needed to achieve Onchocerciasis elimination where CDTi effectiveness is suboptimal. Hence the need for this research work on elimination and control of Onchocerciasis. This study was a cross-sectional experimental study carried out to investigate the therapeutic efficiency of some selected treatment options of Onchocerciasis prevalent in selected endemic areas of Imo State, Southeastern Nigeria. The multistage sampling technique was adopted to select samples for the study. All infected subjects used for this study gave an informed consent to be part of the study. Accurate screening methods were used to identify subjects with detectable microfilariae that were positive and highly sensitive to the diagnostic tests. A total of one thousand five hundred and thirty (1,530) inhabitants of the studied communities (Umulolo, Amuro, Ihube, Okwe, Umuna, Ezelu, Nzerem, Umuihi, Umuneke and Umulewe) were screened for the infection. Out of these, the number infected by Onchocerca volvulus in the ten studied areas were five hundred and ninety-two (592). The infected subjects were sampled evenly and assigned into subgroups to receive treatment with doses of Ivermectin, Doxycycline as well as Morinda lucida and Indigo tinctoria plant extracts. Samples from the treated subjects were collected, screened and assessed for elimination of microfilarial loads. Results showed that higher number of infected subjects (91.1%) benefited from treatment with oral dose of Doxycycline and had their clinical signs disappeared as compared with 82.96% (Ivermectin), 47.2% (Morinda lucida) and 46.5% (Indigo tinctoria) benefited subjects. Statistical analysis using the Duncan Multiple Range Test also showed significant differences p ≥ 0.01 in the treatment options administered. It was however recommended that more improved treatment options are needed to ensure massive control measures and total eradication of the infection. Keywords: Onchocerciasis, therapeutic, microfilariae, screening, endemic, elimination.

Epilepsy and nodding syndrome in association with an Onchocerca volvulus infection drive distinct immune profile patterns.

Previous studies have described the association of onchocerciasis (caused by Onchocerca volvulus) with epilepsy, including nodding syndrome, although a clear etiological link is still missing. Cases are found in different African countries (Tanzania, South Sudan, Uganda, Democratic Republic of the Congo, Central African Republic and Cameroon). In our study we investigated immunological parameters (cytokine, chemokine, immunoglobulin levels) in individuals from the Mahenge area, Tanzania, presenting with either epilepsy or nodding syndrome with or without O. volvulus infection and compared them to O. volvulus negative individuals from the same endemic area lacking neurological disorders. Additionally, cell differentiation was performed using blood smears and systemic levels of neurodegeneration markers, leiomodin-1 and N-acetyltyramine-O, β-glucuronide (NATOG) were determined. Our findings revealed that cytokines, most chemokines and neurodegeneration markers were comparable between both groups presenting with epilepsy or nodding syndrome. However, we observed elevated eosinophil percentages within the O. volvulus positive epilepsy/nodding syndrome patients accompanied with increased eosinophilic cationic protein (ECP) and antigen-specific IgG levels in comparison to those without an O. volvulus infection. Furthermore, highest levels of NATOG were found in O. volvulus positive nodding syndrome patients. These findings highlight that the detection of distinct biomarkers might be useful for a differential diagnosis of epilepsy and nodding syndrome in O. volvulus endemic areas. Trial-registration: NCT03653975.

Application of loop mediated isothermal amplification (LAMP) assays for the detection of Onchocerca volvulus, Loa loa and Mansonella perstans in humans and vectors.

Conventional diagnosis of filarial infections is based on morphological identification of microfilariae using light microscopy and requires considerable expertise, is time-consuming, and can be subjective. Loop-mediated isothermal amplification (LAMP) has advantages over microscopy or PCR because of its operational simplicity, rapidity and versatility of readout options. LAMP assays represent a major step forward in improved filarial diagnostic tools suitable for low resource settings and field applicability. The study goal was to retrospectively evaluate the performance and suitability of the O-150, RF4, and Mp419 LAMP assays for diagnosing Onchocerca volvulus, Loa loa and Mansonella perstans infections, respectively, in humans and vectors under experimental and natural field conditions. Surveys were conducted in four health districts of Cameroon using skin snip and thick blood film methods to detect skin (O. volvulus) and blood (L. loa and M. perstans) dwelling microfilaria in humans. Engorged vectors (Simulium spp., Chrysops spp., and Culicoides spp.) were evaluated by LAMP. Dissected, wild-caught vectors were also analyzed. LAMP showed a prevalence of 40.4% (O. volvulus), 17.8% (L. loa) and 36.6% (M. perstans) versus 20.6% (O. volvulus), 17.4% (L. loa) and 33.8% (M. perstans) with microscopy. Simulium spp. were dissected for microscopy and pooled for LAMP. The O-150 LAMP assay infection rate was 4.3% versus 4.1% by microscopy. Chrysops spp. were dissected and analyzed individually in the LAMP assay. The RF4 LAMP assay infection rate was 23.5% versus 3.3% with microscopy. The RF4 LAMP assay also detected parasites in Chrysops spp. fed on low microfilaremic volunteers. The Mp419 LAMP assay infection rate was 0.2% for C. milnei and 0.04% for C. grahamii, while three other species were LAMP-negative. The sensitivity, species specificity, rapidity and ease of its use of these filarial LAMP assays, and validation of their performance in the field support use as alternatives to microscopy as diagnostic and surveillance tools in global health programs aimed to eliminate onchocerciasis.

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.

Pharmacokinetics of oral moxidectin in individuals with Onchocerca volvulus infection.

Onchocerciasis ("river blindness"), is a neglected tropical disease caused by the filarial nematode Onchocerca volvulus and transmitted to humans through repeated bites by infective blackflies of the genus Simulium. Moxidectin was approved by the United States Food and Drug Administration in 2018 for the treatment of onchocerciasis in people at least 12 years of age. The pharmacokinetics of orally administered moxidectin in 18- to 60-year-old men and women infected with Onchocerca volvulus were investigated in a single-center, ivermectin-controlled, double-blind, randomized, single-ascending-dose, ascending severity of infection study in Ghana. Participants were randomized to either a single dose of 2, 4 or 8 mg moxidectin or ivermectin. Pharmacokinetic samples were collected prior to dosing and at intervals up to 12 months post-dose from 33 and 34 individuals treated with 2 and 4 mg moxidectin, respectively and up to 18 months post-dose from 31 individuals treated with 8 mg moxidectin. Moxidectin plasma concentrations were determined using high-performance liquid chromatography with fluorescence detection. Moxidectin plasma AUC0-∞ (2 mg: 26.7-31.7 days*ng/mL, 4 mg: 39.1-60.0 days*ng/mL, 8 mg: 99.5-129.0 days*ng/mL) and Cmax (2mg, 16.2 to17.3 ng/mL, 4 mg: 33.4 to 35.0 ng/mL, 8 mg: 55.7 to 74.4 ng/mL) were dose-proportional and independent of severity of infection. Maximum plasma concentrations were achieved 4 hours after drug administration. The mean terminal half-lives of moxidectin were 20.6, 17.7, and 23.3 days at the 2, 4 and 8 mg dose levels, respectively. We found no relationship between severity of infection (mild, moderate or severe) and exposure parameters (AUC0-∞ and Cmax), T1/2 and Tmax for moxidectin. Tmax, volume of distribution (V/F) and oral clearance (CL/F) are similar to those in healthy volunteers from Europe. From a pharmacokinetic perspective, moxidectin is an attractive long-acting therapeutic option for the treatment of human onchocerciasis.

Bacteriome Diversity of Blackflies' Gut and Association with Onchocerca volvulus, the Causative Agent of Onchocerciasis in Mbam Valley (Center Region, Cameroon).

Vector control using larvicides is the main alternative strategy to address limits of preventive chemotherapy using ivermectin for the control of onchocerciasis. However, it remains substantially limited by implementation difficulties, ecological concerns and the resistance of vector populations. Therefore, efficient and environmentally safe alternative control strategies are still needed. This study explores the composition of the blackfly bacteriome and its variability in the presence of Onchocerca volvulus infection, in order to determine their potential as a novel vector control-based approach to fight onchocerciasis. An entomological survey of a collection of samples was performed in the Bafia health district, a historical endemic focus for onchocerciasis in Cameroon. A total of 1270 blackflies were dissected and the infection rate was 10.1%, indicative of ongoing transmission of onchocerciasis in the surveyed communities. Sequencing process of blackflies’ gut DNA for bacteria screening revealed 14 phyla and 123 genera, highlighting the diversity of gut blackflies bacterial communities. Eight bacteria formed the core of blackfly bacteriome and Wolbachia was the predominant genus with 73.4% of relative abundance of blackflies’ gut bacterial communities. Acidomonas and Roseanomas genera were significantly abundant among infected blackflies (p = 0.01), whereas other genera such as Brevibacterium and Fructobacillus were associated with the absence of infection (p = 0.0009). Differences in gut bacterial distribution of blackflies according to their infection status by the parasite suggest a causal relationship between the bacteriome composition and the onset of blackflies’ infection by O. volvulus or vice versa. Blackfly native bacteria are then potentially involved in infection by O. volvulus, either by facilitating or preventing the parasite infestation of the vector. These bacteria represent an interesting potential as a biological tool/target for a novel approach of vector control to fight onchocerciasis.

A Reevaluation of the Tolerability and Effects of Single-Dose Ivermectin Treatment on Onchocerca volvulus Microfilariae in the Skin and Eyes in Eastern Ghana.

ABSTRACT.Mass administration of ivermectin (IVM) has significantly reduced onchocerciasis prevalence, intensity, and morbidity in most endemic areas. Most IVM clinical trials were performed long ago in persons with high-intensity infections that are uncommon in West Africa today. This cohort treatment study recruited participants from a hypoendemic area in eastern Ghana to reevaluate the efficacy and tolerability of IVM with a special focus on the kinetics of microfilaria (Mf) clearance. Mf in the skin and anterior chambers (AC) were assessed by skin snip and slit lamp examinations at baseline and at 3 and 6 months after treatment with IVM 150 μg/kg. Most participants (184–231, 79.7%) enrolled were treatment-naïve. The baseline geometric mean skin Mf count was 12.67/mg (range 3–86). Although persons with MfAC at baseline (64/231, 27%) had significantly higher skin Mf counts than people without MfAC, 7 of 39 (15%) of persons with skin Mf counts in the range of 3–5 Mf/mg had MfAC. Skin Mf were detected in 14% (31/218) and 45% (96/216) of participants 3 and 6 months after IVM treatment, respectively. MfAC were detected in 12 of 212 (5.7%) study participants at 6 months. 81% (187 of 231) of participants experienced 439 adverse events within 7 days after treatment; all adverse events were mild (96.1%) or moderate. This study has provided new data on the kinetics of Mf in the skin and eyes after IVM treatment of persons with light to moderate intensity Onchocerca volvulus infections that are common in Africa at this time.

Tandem Use of OvMANE1 and Ov-16 ELISA Tests Increases the Sensitivity for the Diagnosis of Human Onchocerciasis.

The current serological test for human onchocerciasis relies on IgG4 reactivity against the parasite Ov-16 antigen, with reported sensitivities of only 60–80%. As control programs move from control to elimination, it is imperative to identify novel molecules that could improve the serodiagnosis reliability of this disease. In this study we compared the sensitivity of total IgG against OvMANE1—a chimeric antigen previously identified as a potential biomarker of human onchocerciasis—with that of an Ov-16 antibody test to detect an Onchocerca volvulus infection in persons presenting with microfilaria in skin snips. One hundred and ninety serum samples were obtained from persons with epilepsy in an onchocerciasis-endemic area at Ituri in the Democratic Republic of Congo where ivermectin has never been distributed. Fifty-nine (31.1%) samples were from individuals with a positive skin snip test; 41 (69.5%) of these 59 samples were positive with the OvMANE1 test and 41 (69.5%) with the Ov-16 test; 30 (50.8%) samples were positive for both tests and in 52 (88.1%) at least one of the tests was positive. Testing the 131 sera from persons with a negative skin snip result revealed that 63 (48.1%) were positive exclusively with the OvMANE1 test, 13 (9.9%) exclusively with the Ov-16 test and 25 (19.1%) with both tests. Nine European samples from individuals without past travel history in onchocerciasis endemic zones and 15 samples from Rwanda, a hypoendemic country for onchocerciasis were all negative for the OvMANE1 and Ov-16 tests. However, the specificity of both tests was difficult to determine due to the lack of a gold standard for antibody tests. In conclusion, the tandem use of OvMANE1 and Ov-16 tests improves the sensitivity of detecting Onchocerca volvulus seropositive individuals but, the OvMANE1 test needs to be further evaluated on samples from a population infected with other helminths to cautiously address its specificity.

The burden of skin disease and eye disease due to onchocerciasis in countries formerly under the African Programme for Onchocerciasis Control mandate for 1990, 2020, and 2030.

Onchocerciasis ("river blindness") can cause severe morbidity, including vision loss and various skin manifestations, and is targeted for elimination using ivermectin mass drug administration (MDA). We calculated the number of people with Onchocerca volvulus infection and onchocercal skin and eye disease as well as disability-adjusted life years (DALYs) lost from 1990 through to 2030 in areas formerly covered by the African Programme for Onchocerciasis Control. Per MDA implementation unit, we collated data on the pre-control distribution of microfilariae (mf) prevalence and the history of control. Next, we predicted trends in infection and morbidity over time using the ONCHOSIM simulation model. DALY estimates were calculated using disability weights from the Global Burden of Disease Study. In 1990, prior to MDA implementation, the total population at risk was 79.8 million with 26.0 million (32.5%) mf-positive individuals, of whom 17.5 million (21.9%) had some form of onchocercal skin or eye disease (2.5 million DALYs lost). By 2030, the total population was predicted to increase to 236.1 million, while the number of mf-positive cases (about 6.8 million, 2.9%), people with skin or eye morbidity (4.2 million, 1.8%), and DALYs lost (0.7 million) were predicted to decline. MDA has had a remarkable impact on the onchocerciasis burden in countries previously under the APOC mandate. In the few countries where we predict continued transmission between now and 2030, intensified MDA could be combined with local vector control efforts, or the introduction of new drugs for mopping up residual cases of infection and morbidity.

Systemic and cerebrospinal fluid immune and complement activation in Ugandan children and adolescents with long-standing nodding syndrome: A case-control study.

ObjectiveNodding syndrome is a poorly understood epileptic encephalopathy characterized by a unique seizure type—head nodding—and associated with Onchocerca volvulus infection. We hypothesized that altered immune activation in the cerebrospinal fluid (CSF) and plasma of children with nodding syndrome may yield insights into the pathophysiology and progression of this seizure disorder.MethodWe conducted a case‐control study of 154 children (8 years or older) with long‐standing nodding syndrome and 154 healthy age‐matched community controls in 3 districts of northern Uganda affected by nodding syndrome. Control CSF samples were obtained from Ugandan children in remission from hematological malignancy during routine follow‐up. Markers of immune activation and inflammation (cytokines and chemokines) and complement activation (C5a) were measured in plasma and CSF using ELISA or Multiplex Luminex assays. O volvulus infection was assessed by serology for anti–OV‐16 IgG levels.ResultsThe mean (SD) age of the population was 15.1 (SD: 1.9) years, and the mean duration of nodding syndrome from diagnosis to enrollment was 8.3 (SD: 2.7) years. The majority with nodding syndrome had been exposed to O volvulus (147/154 (95.4%)) compared with community children (86/154 (55.8%)), with an OR of 17.04 (95% CI: 7.33, 45.58), P < .001. C5a was elevated in CSF of children with nodding syndrome compared to controls (P < .0001). The levels of other CSF markers tested were comparable between cases and controls after adjusting for multiple comparisons. Children with nodding syndrome had lower plasma levels of IL‐10, APRIL, CCL5 (RANTES), CCL2, CXCL13, and MMP‐9 compared with community controls (P < .05 for all; multiple comparisons). Plasma CRP was elevated in children with nodding syndrome compared to community children and correlated with disease severity.SignificanceNodding syndrome is associated with exposure to O. volvulus. Compared to controls, children with long‐standing symptoms of nodding syndrome show evidence of complement activation in CSF and altered immune activation in plasma.

Onchocerca volvulus infection among ivermectin-treated population in a rural setting in Edo State, Nigeria

Background: West Africa includes the most endemic areas in the world with Nigeria being one of the largest countries of West Africa that has been reported to have a high incidence of onchocerciasis. Aim: The aim of this study was to determine Onchocerca volvulus infection among ivermectin-treated population in Ekpan community, Edo State, Nigeria. Setting and Design: A total of 105 participants including 60 males and 45 females with an age range of 15–81 years were recruited in the study. Random sampling technique was employed in the recruitment of participants. Materials and Methods: Two skin snip specimens were taken from the left and right iliac crests of each participant into a microtube containing physiological saline. The skin snips were processed using standard technique and examined microscopically for microfilariae of O. volvulus. Statistical Analysis: The data collected were analyzed using the Chi-square (X2) test and odd ratio. The statistical package used was GraphPad INSTAT. Results: An overall prevalence of 74.3% of O. volvulus infection was observed among ivermectin-treated subjects in Ekpan. Age, occupation, noncompliance of ivermectin treatment, and source of water significantly affected the prevalence of O. volvulus infection among ivermectin-treated population in Ekpan (P < 0.05). Conclusion: Effective distribution of ivermectin and strict compliance of ivermectin treatment are advocated as these efforts will go a long way at controlling as well as reducing the effects of onchocerciasis in this community.

Persons with onchocerciasis-associated epilepsy and nodding seizures have a more severe form of epilepsy with more cognitive impairment and higher levels of Onchocerca volvulus infection.

Following previous reports of very high epilepsy prevalence in the onchocerciasis-endemic villages in Maridi County, South Sudan, a study was conducted to investigate the association between the level of Onchocerca volvulus infection, epilepsy, and related outcomes. In December 2018, persons with epilepsy (PWE) were recruited from villages where an epilepsy prevalence of 4.4% (range: 3.5-11.9%) was documented. We enrolled 318 participants from whom two skin snips were taken for microscopic detection of O. volvulus microfilariae (mf). Seizure history was obtained for all PWE and their degree of disability assessed using the modified Rankin scale. Almost all (84.9%) PWE had detectable mf in their skin snips. Onchocerciasis-infected PWE experienced nodding seizures more often than uninfected PWE (p=0.034). Moreover, persons with nodding seizures had more frequent seizures (p<0.001) and higher disability scores (p<0.001), and were more often cognitively impaired and younger at the time of their first epileptic seizure (nine years vs 12 years, p<0.001) compared to PWE without nodding seizures. Based on multivariate models, nodding seizures were associated with higher mf densities (aOR: 1.022; 95%CI: 1.005-1.041). Epilepsy onset at a younger age was associated with a worse outcome. Higher frequency of seizures, longer duration of epilepsy and younger age were associated with increased disability. Regular antiepileptic drug use was associated with better cognitive and disability outcomes. PWE with nodding seizures have a more severe form of onchocerciasis-associated epilepsy, with earlier seizure onset and higher levels of O. volvulus infection. Younger PWE were prone to worse epilepsy outcomes, which would be prevented with regular antiepileptic treatment.

Urinary N-acetyltyramine-O,β-glucuronide in Persons with Onchocerciasis-Associated Epilepsy.

We investigated urinary N-acetyltyramine-O,β-glucuronide (NATOG) levels as a biomarker for active Onchocerca volvulus infection in an onchocerciasis-endemic area in the Democratic Republic of Congo with a high epilepsy prevalence. Urinary NATOG was measured in non-epileptic men with and without O. volvulus infection, and in O. volvulus-infected persons with epilepsy (PWE). Urinary NATOG concentration was positively associated with microfilarial density (p < 0.001). The median urinary NATOG concentration was higher in PWE (3.67 µM) compared to men without epilepsy (1.74 µM), p = 0.017; and was higher in persons with severe (7.62 µM) compared to mild epilepsy (2.16 µM); p = 0.008. Non-epileptic participants with and without O. volvulus infection had similar NATOG levels (2.23 µM and 0.71 µM, p = 0.426). In a receiver operating characteristic curve analysis to investigate the diagnostic value of urinary NATOG, the area under the curve was 0.721 (95% CI: 0.633–0.797). Using the previously proposed cut-off value of 13 µM to distinguish between an active O. volvulus infection and an uninfected state, the sensitivity was 15.9% and the specificity 95.9%. In conclusion, an O. volvulus infection is associated with an increased urinary NATOG concentration, which correlates with the individual parasitic load. However, the NATOG concentration has a low discriminating power to differentiate between infected and uninfected individuals.

Situation analysis of onchocerciasis in Cameroon: a protocol for systematic review of epidemiological studies and impact of disease control interventions

BackgroundMany control methods have been implemented to tackle onchocerciasis and great successes have been achieved, leading to a paradigm shift from control of morbidity to interruption of transmission and ultimately elimination. The mandate of the African Programme for Onchocerciasis Control (APOC) ended in 2015, and endemic countries are to plan and conduct elimination activities by themselves, with technical assistance by the Expanded Special Project for Elimination of Neglected Tropical Diseases (ESPEN). To this end, an elimination expert committee was set up in Cameroon in 2018. This committee identified the need to update the data on the current situation of onchocerciasis. The present study aims to systematically review and report all available epidemiological data, including prevalence, intensity and transmission of onchocerciasis to provide pertinent information that will be useful to design optimal strategies to achieve onchocerciasis elimination in Cameroon.MethodsPubMed/MEDLINE, EMBASE and Web of Science will be searched from inception onwards. Grey literature will be identified through Google Scholar searches, dissertation databases and other relevant documents such as government reports. Eligible studies will be mostly observational, including cohort and cross-sectional surveys. No limitations will be imposed on publication status and study period. The primary outcomes will be (1) the prevalence and intensity of Onchocerca volvulus infection in humans, (2) transmission intensity and (3) impact of interventions on prevalence, intensity and transmission of onchocerciasis. Secondary outcomes will be environmental and socio-demographic factors supporting the primary outcomes. Two reviewers will independently screen all citations, full-text articles and abstract data. Potential conflicts will be resolved through discussion. Methodological quality including bias will be appraised using appropriate approaches. A narrative synthesis will describe quality and content of the epidemiological evidence. Prevalence and intensity of infection estimates will be stratified according to gender, age, geographical location and year of publication.DiscussionThis study will provide the health authorities as well as the scientific community with up-to-date information about the epidemiological situation of onchocerciasis in Cameroon. Understanding the spatiotemporal dynamics of the infection will help to define alternative and complementary strategies to accelerate onchocerciasis elimination in the country. Results of this review will also be used to update existing epidemiological models for onchocerciasis in order to fine-tune predictions of elimination timeframes in the country.Systematic review registrationThis protocol is under registration review in PROSPERO.

Antibody responses against the vaccine antigens Ov-103 and Ov-RAL-2 are associated with protective immunity to Onchocerca volvulus infection in both mice and humans.

BackgroundThe current strategy for the elimination of onchocerciasis is based on annual or bi-annual mass drug administration with ivermectin. However, due to several limiting factors there is a growing concern that elimination of onchocerciasis cannot be achieved solely through the current strategy. Additional tools are critically needed including a prophylactic vaccine. Presently Ov-103 and Ov-RAL-2 are the most promising vaccine candidates against an Onchocerca volvulus infection.Methodology/Principal findingsProtection induced by immunization of mice with the alum-adjuvanted Ov-103 or Ov-RAL-2 vaccines appeared to be antibody dependent since AID-/- mice that could not mount antigen-specific IgG antibody responses were not protected from an Onchocerca volvulus challenge. To determine a possible association between antigen-specific antibody responses and anti-larvae protective immunity in humans, we analyzed the presence of anti-Ov-103 and anti-Ov-RAL-2 cytophilic antibody responses (IgG1 and IgG3) in individuals classified as putatively immune, and in infected individuals who developed concomitant immunity with age. It was determined that 86% of putatively immune individuals and 95% individuals with concomitant immunity had elevated IgG1 and IgG3 responses to Ov-103 and Ov-RAL-2. Based on the elevated chemokine levels associated with protection in the Ov-103 or Ov-RAL-2 immunized mice, the profile of these chemokines was also analyzed in putatively immune and infected individuals; both groups contained significantly higher levels of KC, IP-10, MCP-1 and MIP-1β in comparison to normal human sera. Moreover, human monospecific anti-Ov-103 antibodies but not anti-Ov-RAL-2 significantly inhibited the molting of third-stage larvae (L3) in vitro by 46% in the presence of naïve human neutrophils, while both anti-Ov-103 and anti-Ov-RAL-2 antibodies significantly inhibited the molting by 70–80% when cultured in the presence of naive human monocytes. Interestingly, inhibition of molting by Ov-103 antibodies and monocytes was only in part dependent on contact with the cells, while inhibition of molting with Ov-RAL-2 antibodies was completely dependent on contact with the monocytes. In comparison, significant levels of parasite killing in Ov-103 and Ov-RAL-2 vaccinated mice only occurred when cells enter the parasite microenvironment. Taken together, antibodies to Ov-103 and Ov-RAL-2 and cells are required for protection in mice as well as for the development of immunity in humans.Conclusions/SignificanceAlum-adjuvanted Ov-103 and Ov-RAL-2 vaccines have the potential of reducing infection and thus morbidity associated with onchocerciasis in humans. The development of cytophilic antibodies, that function in antibody-dependent cellular cytotoxicity, is essential for a successful prophylactic vaccine against this infection.

Performance evaluation of 3 serodiagnostic peptide epitopes and the derived multi-epitope peptide OvNMP-48 for detection of Onchocerca volvulus infection

Current diagnostic tools to determine infection with the helminth parasite Onchocerca volvulus have limited performance characteristics. In previous studies, a proteome-wide screen was conducted to identify linear epitopes in this parasite’s proteome, resulting in the discovery of 1110 antigenic peptide fragments. Here, we investigated three of these peptides using peptide ELISA’s and evaluated their sensitivity and specificity. Epitope mapping was performed, and peptides were constructed that contained only the minimal epitope, flanked by a linker. Investigation of the performance of these minimal epitope peptides demonstrated that all three of them have a specificity (as defined by lack of response in non-helminth-infected individuals) of 100%, low cross-reactivity (5.6%, 5.6%, and 9.3%, respectively), but low sensitivity (36.9%, 46.5%, and 41.2%, respectively). Some cross-reactivity was observed in samples from individuals infected with soil-transmitted helminths or Brugia malayi. Combining these three minimal epitopes in a single peptide, called OvNMP-48, resulted in a performance that exceeded the sum of the individual epitopes, with a sensitivity of 76.0%, a specificity of 97.4%, and a cross-reactivity of 11.1%. Cross-reactivity was observed in some STH and Brugia malayi-infected individuals. This work opens the opportunity to start exploring how these novel linear epitope markers might become part of the O. volvulus diagnostic toolbox.

High Prevalence of Epilepsy in Onchocerciasis Endemic Communities of Ngie: Lack of Association with Taeniasis but Strong Indicators of Hereditary Factors and Characteristics of Onchocerciasis Associated Epilepsy Observed

Epilepsy, a neurological condition which affects individuals of all ages has been widely reported to be caused by parasitic, fungal, bacterial or viral infectious diseases of the Central Nervous System (CNS). Taenia solium infection otherwise known as neurocysticercosis in taeniasis endemic zones, Onchocerca volvulus infection in onchocerciasis meso/hyperendemic areas in Africa and other infectious agents have been highly incriminated in different parts of the world. Epilepsy remains an important but neglected public health problem in many countries. Ngie sub division is endemic for onchocerciasis and the people are highly involved in pig farming and pork consumption. This study aimed to determine the prevalence of epilepsy in Ngie, investigate its association with Taenia solium infection as well as other risk factors.

Onchocerca volvulus as a risk factor for developing epilepsy in onchocerciasis endemic regions in the Democratic Republic of Congo: a case control study

BackgroundA high prevalence of epilepsy has been observed in onchocerciasis endemic areas in the Democratic Republic of Congo (DRC). With this study we aimed to investigate whether Onchocerca volvulus infection is a risk factor for developing epilepsy in onchocerciasis endemic regions in the DRC.MethodsBetween October and December 2015, a multi-centre case control study was performed in onchocerciasis endemic health zones (HZ) in the DRC: one study site was situated in Tshopo Province in the HZ of Wanierukula (village of Salambongo) where there had been 13 annual community distributions of treatment with ivermectin (CDTI), a second was situated in Ituri Province in the HZ of Logo (village of Draju) where ivermectin had never been distributed and in the HZ of Rethy (village of Rassia) where there had been THREE CDTI annual campaigns before the study. Individuals with unprovoked convulsive epilepsy of unknown etiology were enrolled as cases (n = 175). Randomly selected healthy members of families without epilepsy cases from the same village and age-groups and were recruited as controls (n = 170).ResultsOnchocerciasis associated symptoms (e.g., itching and abnormal skin) were more often present in cases compared to controls (respectively, OR = 2.63, 95% CI: 1.63–4.23, P < 0.0001 and OR = 3.23, 95% CI: 1.48–7.09, P = 0.0034). A higher number of cases was found to present with microfilariae in skin snips and with O. volvulus IgG4 antibodies in the blood compared to controls. Moreover, the microfilariae load in skin snips was 3–10 times higher in cases than controls.ConclusionsThis case control study confirms that O. volvulus is a risk factor for developing epilepsy in onchocerciasis endemic regions in the DRC.