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Background: This study examined onchocerciasis transmission in Kwanware and Ottou in the Wenchi Health District of Ghana, where persistent onchocercal microfilariae (mf) levels have been reported since 2012., Methods: This study was conducted from 2019 to 2021 and involved the following: (i) reviewing past records of ivermectin mass drug administration (MDA); (ii) conducting a treatment coverage evaluation survey (CES); (iii) conducting key informant interviews; (iv) prospecting blackfly breeding sites; (v) collecting and dissecting blackflies; and (vi) conducting parasitological and serological surveys., Results: (i) The review indicated ongoing MDA treatment for the past 27 years, with a reported coverage of over 65% in the last 17 yearly rounds; (ii) estimated treatment coverage by the CES in 2019 was 71.3%, with most of those not taking medicine stating that they were not offered; (iii) however, the key informant interviews revealed insufficiencies in reaching a significant number of people for treatment due to remote settlement, mobility, transport logistical issues, failure to register some people for treatment, leading to a false impression of good coverage, and a short distribution time; (iv) the most productive breeding was found within 5 km of Kwanware-Ottou; and (v) blackfly daily biting rates were highest in Kwanware and Ottou, with 199 and 160 bites per day, respectively. Infection in blackflies was found only in Kwanware and Ottou, with infectivity rates of 5.9‰ (per 1000) and 6.7‰, respectively. (vi) The mf prevalence in Ottou and Kwanware, respectively, was 40.0% and 30.0% among adults aged ≥ 20 years, and the anti-(Onchocerca volvulus) Ov16 IgG4 antibodies seroprevalence rates were 8.3% and 13.3% among children aged 5-9 years. These values were reduced to undetectable levels at a radius of 10 km from Ottou., Conclusions: This study confirms that active onchocerciasis transmission centres on Kwanware/Ottou and is confined to a 10 km radius despite 27 yearly treatment rounds. The main contributing factors are suboptimal coverage and high biting rates. Identifying and targeting such a focus with a combination of interventions will be cost-effective in accelerating onchocerciasis elimination in Ghana., (© 2024. The Author(s).)

Background: Human onchocerciasis remains a public health problem in Ghana. Mass drug administration (MDA) with ivermectin (IVM) has reduced disease morbidity and prevalence, but the transmission of onchocerciasis remains ongoing in several endemic foci. We investigated parasite transmission in some endemic communities in Ghana that had received > 18 rounds of annual MDA with IVM and determined the species composition of black fly (Simulium damnosum) vectors in these areas., Methods: Adult female black flies were collected using human landing catches and identified as either forest or savanna species using morpho-taxonomic keys. The adult flies underwent dissection to determine their parity and detect any O. volvulus larvae, followed by the calculation of entomological indices. Simulium damnosum s.l. larvae were collected and preserved in freshly prepared Carnoy's fixative and were later used for cytotaxonomic studies., Results: A total of 9,983 adult flies were caught: 6,569 and 3,414 in the rainy and dry seasons respectively. Black fly biting activities over the study period showed bimodal or trimodal patterns. The highest monthly biting rate (MBR) of 10,578.75 bites/person/month was recorded in July in Beposo, while the highest monthly transmission potential of 100.69 infective bites/person/month was recorded in Asubende in August. Morphological analysis of 2,032 flies showed that 99.8% (2,028) of the flies were savanna species, with only 4 (0.2%) adult flies being of the forest species. Cytogenetic studies on 114 black fly larvae revealed three cytospecies (Simulium damnosum s.s., S. sirbanum and S. sanctipauli) in the study area., Conclusions: The present studies confirmed an ongoing transmission of onchocerciasis in the study communities except Abua-1. It also provides further information on biting behaviors and onchocerciasis transmission indices in the study communities. Further, our data confirmed the savanna species (S. damnosum s.s. and S. sirbanum) of the S. damnosum s.l. to be the major vectors of onchocerciasis in the study areas, with only an occasional influx of forest cytotypes., (© 2024. The Author(s).)

Background: The main vectors of onchocerciasis in Africa are Simulium damnosum sensu lato, which transmit the causative agent Onchocerca volvulus. The force of transmission is driven by the vector density, hence influencing the disease prevalence and intensity. Onchocerciasis is currently targeted for elimination using mass drug administration (MDA) of ivermectin, a potent microfilaricide. MDA in Cameroon began in 1987 in the Vina Valley, an endemic cross-border area with Chad, known for high vector densities and precontrol endemicity. Evaluations in 2008-2010 in this area showed ongoing transmission, while border areas in Chad were close to interrupting transmission. This study aimed to evaluate transmission in this area after several rounds of MDA since the last evaluation surveys., Methods: Black flies were collected by human landing catches at seven border sites in Cameroon, twice a week, from August 2021 to March 2022. A fraction of the flies was dissected for parity assessment and identification of Onchocerca larval stages. The transmission indices were estimated. Black fly larvae were also collected from the breeding sites at the fly catching sites and identified to species level by cytotaxonomy., Results: A total of 14,303 female flies were collected, and 6918 were dissected. Of these, 4421 (64.0%) were parous. The total biting rates were high, reaching up to 16,407 bites/person/study period, and transmission potential (third-stage larvae (L3) from head/all L3) were 367/702, 146/506, 51/55, 20/32, 0/3, 0/0, and 0/0 infective larvae/person, respectively, for Mbere-Tchad, Babidan, Hajam/V5, Gor, Djeing, Touboro, and Koinderi. Infectivity rates (L3 from head) were 16.00, 12.75, 5.15, and 4.07 infective females (L3H)/1000 parous flies for Haijam, Mbere-Tchad, Babidan, and Gor, respectively. These values exceed the World Health Organization (WHO) thresholds of ≤ 20 annual transmission potential (ATP) or < 1 infective female/1000 parous females. The major vectors identified were Simulium damnosum sensu stricto, S. squamosum, and for the first time in the area, S. yahense., Conclusions: More than 20 years of MDA has not eliminated onchocerciasis in the study area; hence, this area is a potential source of reintroduction of onchocerciasis in Chad and would require alternative treatment strategies. Many factors such as MDA efficiency, effectiveness of ivermectin, and cytospecies composition may be contributing to transmission persistence., (© 2024. The Author(s).)

Background: 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., Methodology/principal Findings: 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., Conclusions/significance: 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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Nikièma et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Epilepsy imposes a substantial burden on the Democratic Republic of Congo (DRC). These challenges encompass the lack of comprehensive disease surveillance, an unresolved understanding of its pathophysiology, economic barriers limiting access to essential care, the absence of epilepsy surgical capabilities, and deeply ingrained societal stigmas. Notably, the national prevalence of epilepsy remains undetermined, with research primarily concentrating on infectious factors like Onchocerca volvulus, leaving other potential causes underexplored. Most patients lack insurance, incurring out-of-pocket expenses that often lead them to opt for traditional medicine rather than clinical care. Social stigma, perpetuated by common misconceptions, intensifies the social isolation experienced by individuals living with epilepsy. Additionally, surgical interventions are unavailable, and the accessibility of anti-seizure medications and healthcare infrastructure remains inadequate. Effectively tackling these interrelated challenges requires a multifaceted approach, including conducting research into region-specific factors contributing to epilepsy, increasing healthcare funding, subsidizing the costs of treatment, deploying mobile tools for extensive screening, launching awareness campaigns to dispel myths and reduce stigma, and promoting collaborations between traditional healers and medical practitioners to enhance local understanding and epilepsy management. Despite the difficulties, significant progress can be achieved through sustained and compassionate efforts to understand and eliminate the barriers faced by epilepsy patients in the region. This review outlines essential steps for alleviating the epilepsy burden in the DRC. PLAIN LANGUAGE SUMMARY: There are not enough resources to treat epilepsy in the DRC. PWEs struggle with stigma and the lack of money. Many of them still use traditional medicine for treatment and hold wrong beliefs about epilepsy. That is why there is a need for more resources to make the lives of PWEs better in the DRC., (© 2024 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Background: Despite 20 years of ivermectin mass distribution in the Mahenge area, Tanzania, the prevalence of onchocerciasis and epilepsy has remained high in rural villages., Objectives: We investigated the efficacy of ivermectin in reducing Onchocerca volvulus microfilariae and predictors for parasitic load following ivermectin treatment in persons with (PWE) and without epilepsy (PWOE)., Methods: Between April and September 2019, 50 PWE and 160 randomly selected PWOE from Msogezi and Mdindo villages participated in a follow-up study. Skin snips were obtained pre (baseline) and three months post-ivermectin treatment., Results: The overall prevalence of O. volvulus positive skin snips at baseline was 49% (103/210), with no significant difference between PWE (58.0%) and PWOE (46.3%); p=0.197. The overall mean microfilarial density was significantly higher at baseline 1.45(95%CI:0.98-2.04)) than three-month post-ivermectin treatment (0.23(95%CI:0.11-0.37), p<0.001. Three months after ivermectin, the microfilarial density had decreased by ≥80% in 54 (81.8%, 95%CI: 72.3-91.4) of the 66 individuals with positive skin snips at baseline. High microfilarial density at baseline was the only significant predictor associated with higher microfilarial density in the post-ivermectin skin snips., Conclusion: Our study reports a decrease in microfilarial density following ivermectin treatment in most individuals. Optimizing ivermectin coverage will address the ongoing onchocerciasis transmission in Mahenge., (© 2022 Bhwana D et al.)

The neglected tropical disease onchocerciasis, or river blindness, is caused by infection with the filarial nematode Onchocerca volvulus. Current estimates indicate that 17 million people are infected worldwide, the majority of them living in Africa. Today there are no non-invasive tests available that can detect ongoing infection, and that can be used for effective monitoring of elimination programs. In addition, to enable pharmacodynamic studies with novel macrofilaricide drug candidates, surrogate endpoints and efficacy biomarkers are needed but are non-existent. We describe the use of a multimodal untargeted mass spectrometry-based approach (metabolomics and lipidomics) to identify onchocerciasis-associated metabolites in urine and plasma, and of specific lipid features in plasma of infected individuals (O. volvulus infected cases: 68 individuals with palpable nodules; lymphatic filariasis cases: 8 individuals; non-endemic controls: 20 individuals). This work resulted in the identification of elevated concentrations of the plasma metabolites inosine and hypoxanthine as biomarkers for filarial infection, and of the urine metabolite cis-cinnamoylglycine (CCG) as biomarker for O. volvulus. During the targeted validation study, metabolite-specific cutoffs were determined (inosine: 34.2 ng/ml; hypoxanthine: 1380 ng/ml; CCG: 29.7 ng/ml) and sensitivity and specificity profiles were established. Subsequent evaluation of these biomarkers in a non-endemic population from a different geographical region invalidated the urine metabolite CCG as biomarker for O. volvulus. The plasma metabolites inosine and hypoxanthine were confirmed as biomarkers for filarial infection. With the availability of targeted LC-MS procedures, the full potential of these 2 biomarkers in macrofilaricide clinical trials, MDA efficacy surveys, and epidemiological transmission studies can be investigated., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Ole Lagatie, Emmanuel Njumbe Ediage, Dirk Van Roosbroeck, Stijn Van Asten, Ann Verheyen, Lieve Dillen, Tom Verhaeghe, Rob Vreeken, Filip Cuyckens and Lieven J. Stuyver are current employees of Janssen Pharmaceutica NV, a Johnson & Johnson company, and may own stock or stock option in that company.

Background: The onchocerciasis focus surrounding the lower Mbam and Sanaga rivers, where Onchocerca volvulus is transmitted by Simulium damnosum s.l. (Diptera: Simuliidae), was historically the largest in the southern regions of Cameroon. Annual community-directed treatment with ivermectin (CDTI) has been taking place since 2000, but recent studies have shown that new infections are occurring in children. We aimed to investigate blackfly biting and O. volvulus transmission rates along the lower Mbam river 16 years after the formal onset of annual CDTI., Methods: Black flies were collected for three consecutive days each month between July 2016 and June 2017 at two riverside villages and two inland sites situated 4.9 km and 7.9 km from the riverside. Specimens collected at each site were dissected on one of the three collection days each month to estimate parity rates and O. volvulus infection rates, while the remaining samples were preserved for pool screening., Results: In total, 93,573 S. damnosum s.l. black flies were recorded biting humans and 9281 were dissected. Annual biting rates of up to 606,370 were estimated at the riverside, decreasing to 20,540 at 7.9 km, while, based on dissections, annual transmission potentials of up to 4488 were estimated at the riverside, decreasing to 102 and 0 at 4.9 km and 7.9 km, respectively. However, pool screening showed evidence of infection in black flies at the furthest distance from the river. Results of both methods demonstrated the percentage of infective flies to be relatively low (0.10-0.36%), but above the WHO threshold for interruption of transmission. In addition, a small number of larvae collected during the dry season revealed the presence of Simulium squamosum E. This is the first time S. squamosum E has been found east of Lake Volta in Ghana, but our material was chromosomally distinctive, and we call it S. squamosum E2., Conclusions: Relatively low O. volvulus infection rates appear to be offset by extremely high densities of biting black flies which are sustaining transmission along the banks of the lower Mbam river., (© 2021. The Author(s).)

Nodding syndrome (NS) is a catastrophic and enigmatic childhood epilepsy, accompanied by multiple neurological impairments and neuroinflammation. Of all the infectious, environmental and psychological factors associated with NS, the major culprit is Onchocerca Volvulus (Ov)-a parasitic worm transmitted to human by blackflies. NS seems to be an 'Autoimmune Epilepsy' in light of the recent findings of deleterious autoimmune antibodies to Glutamate receptors and to Leiomodin-I in NS patients. Moreover, we recently found immunogenetic fingerprints in HLA peptide-binding grooves associate with protection or susceptibility to NS. Macrophage migration inhibitory factor (MIF) is an immune-regulatory cytokine playing a central role in modulating innate and adaptive immunity. MIF is also involved in various pathologies: infectious, autoimmune and neurodegenerative diseases, epilepsy and others. Herein, two functional polymorphisms in the MIF gene, a -794 CATT5-8 microsatellite repeat and a -173 G/C single-nucleotide polymorphism, were assessed in 49 NS patients and 51 healthy controls from South Sudan. We also measured MIF plasma levels in established NS patients and healthy controls. We discovered that the frequency of the high-expression MIF -173C containing genotype was significantly lower in NS patients compared to healthy controls. Interestingly however, MIF plasma levels were significantly elevated in NS patients than in healthy controls. We further demonstrated that the HLA protective and susceptibility associations are dominant over the MIF association with NS. Our findings suggest that MIF might have a dual role in NS. Genetically controlled high-expression MIF genotype is associated with disease protection. However, elevated MIF in the plasma may contribute to the detrimental autoimmunity, neuroinflammation and epilepsy., Competing Interests: The authors have declared that no competing interests exist. Author Lul P. Riek was unavailable to confirm their authorship contributions. On their behalf, the corresponding author has reported their contributions to the best of their knowledge.

Background: Molecular xenomonitoring (MX), the detection of parasite nucleic acid in the vector population, is recommended for onchocerciasis surveillance in elimination settings. However, the sensitivity of MX for detecting onchocerciasis-positive communities has not previously been evaluated. MX may have additional applications for control programmes but its utility is restricted by a limited understanding of the relationship between MX results and human prevalence., Methods: We conducted a systematic review of studies reporting the prevalence of Onchocerca volvulus DNA in wild-caught Simulium spp. flies (MX rate) and corresponding prevalence of microfilaria (mf) in humans. We evaluated the sensitivity of MX for detecting onchocerciasis-positive communities and describe the characteristics of studies with reduced sensitivity. We conducted a linear regression to evaluate the relationship between mf prevalence and MX rate., Results: We identified 15 relevant studies, with 13 studies comprising 34 study communities included in the quantitative analyses. Most communities were at advanced stages towards elimination and had no or extremely low human prevalence. MX detected positive flies in every study area with >1% mf prevalence, with the exception of one study conducted in the Venezuelan Amazonian focus. We identified a significant relationship between the two measurements, with mf prevalence accounting for half of the variation in MX rate (R2 0.50, p<0.001)., Conclusion: MX is sensitive to communities with ongoing onchocerciasis transmission. It has potential to predict human mf prevalence, but further data is required to understand this relationship, particularly from MX surveys conducted earlier in control programmes before transmission has been interrupted., Competing Interests: The authors have declared that no competing interests exist.

Nodding syndrome is one of several forms of onchocerciasis-associated epilepsy (OAE) seen among children in areas formerly hyperendemic for the transmission of Onchocerca volvulus. These forms of epilepsy are highly prevalent and clustered in certain villages located close to blackfly (Diptera: Simuliidae) breeding sites. OAE presents with a wide spectrum of seizures, including generalized tonic-clonic and head nodding seizures, impaired cognitive function, growth stunting and delayed puberty. In 2014, the present authors published a perspective paper in this journal which hypothesized that nodding syndrome may be caused by either a neurotropic virus transmitted by blackflies or an endosymbiont present within the O. volvulus parasite. Seven years later, this critical review presents progress in nodding syndrome research, and assesses whether it is still plausible that a neurotropic virus or endosymbiont could be the cause., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Infections with Onchocerca volvulus nematodes remain a threat in Sub-Saharan Africa after three decades of ivermectin mass drug administration. Despite this effort, there is still an urgent need for understanding the parasite biology especially the mating behaviour and nodule formation as well as the development of more potent drugs that can clear the developmental (L3, L4, L5) and adult stages of the parasite and inhibit parasite reproduction and behaviour., Methodology/principal Findings: Prior to culture, freshly harvested O. volvulus L3 larvae from dissected Simulium damnosum flies were purified by centrifugation using a 30% Percoll solution to eliminate fly tissue debris and contaminants. Parasites were cultured in both cell-free and cell-based co-culture systems and monitored daily by microscopic visual inspection. Exhausted culture medium was replenished every 2-3 days. The cell-free culture system (DMEM supplemented with 10% NCS) supported the viability and motility of O. volvulus larvae for up to 84 days, while the co-culture system (DMEM supplemented with 10% FBS and seeded on LLC-MK2 feeder cells) extended worm survival for up to 315 days. Co-culture systems alone promoted two consecutive parasite moults (L3 to L4 and L4 to L5) with highest moulting rates (69.2±30%) observed in DMEM supplemented with 10% FBS and seeded on LLC-MK2 feeder cells, while no moult was observed in DMEM supplemented with 10% NCS and seeded on LEC feeder cells. In DMEM supplemented with 10% FBS and seeded on LLC-MK2 feeder cells, O. volvulus adult male worms attached to the vulva region of adult female worms and may have mated in vitro. Apparent early initiation of nodulogenesis was observed in both DMEM supplemented with 10% FBS and seeded on LLC-MK2 and DMEM supplemented with 10% NCS and seeded on LLC-MK2 systems., Conclusions/significance: The present study describes an in vitro system in which O. volvulus L3 larvae can be maintained in culture leading to the development of adult stages. Thus, this in vitro system may provide a platform to investigate mating behaviour and early stage of nodulogenesis of O. volvulus adult worms that can be used as additional targets for macrofilaricidal drug screening., Competing Interests: None

Background: Ivermectin-based preventive chemotherapy (PC) is distributed annually to all at-risk populations eligible for ivermectin treatment to control and/or eliminate onchocerciasis. Information on the impact of mass ivermectin administration on onchocerciasis transmission is scanty, and it is tricky to appreciate the progress towards elimination and engage corrective measures. To fill that gap in the Centre Region in Cameroon, the current onchocerciasis endemicity level in the Ndikinimeki Health District after about two decades of mass treatments was assessed., Methods: A cluster-based cross-sectional survey was carried out in the Ndikinimeki Health District and all volunteers aged ≥ 5 years were (i) interviewed on their compliance to ivermectin over the past five years and (ii) underwent clinical (nodule palpation and visual search for onchocercal lesions) and parasitological examinations (skin snip) for onchocerciasis., Results: The overall Onchocerca volvulus prevalence was 7.0% (95% CI: 5.2-9.3%). The prevalence of the disease was significantly higher in the communities Kiboum 1 and Kiboum 2 compared to the other communities (highest prevalence in Makénéné Town Water: 8.5%; 95% CI: 2.3-20.4%) (χ 2 = 51.314, df = 11, P = 0.0001). The proportion of systematic non-compliers to ivermectin was 23.3% (95% CI: 19.9-27.1%) among individuals interviewed. In the sentinel sites (Kiboum communities), onchocerciasis prevalence decreased from 95.2% (95% CI: 88.3-98.1%) to 23.7% (95% CI: 14.7-36.0%)., Conclusions: This study has revealed that the Ndikinimeki Health District is hypo-endemic for onchocerciasis after about two decades of preventive chemotherapy. However, transmission is ongoing, with potential hotspots in the Kiboum 1 and Kiboum 2 communities, which are known as first-line communities (closest to the breeding sites of the vector). Alternative or complementary strategies to annual ivermectin appear compulsory to accelerate the momentum towards onchocerciasis elimination.

Background: Ivermectin is an excellent microfilaricide against Onchocerca volvulus. However, in some regions, long term use of ivermectin has resulted in sub-optimal responses to the treatment. More data to properly document the phenomenon in various contexts of ivermectin mass drug administration (IVM-MDA) is needed. Also, there is a need to accurately monitor a possible repopulation of skin by microfilariae following treatment. Skin snip microscopy is known to have a low sensitivity in individuals with light infections, which can be the case following treatment. This study was designed with two complementary objectives: (i) to assess the susceptibility of O. volvulus microfilariae to ivermectin in two areas undergoing IVM-MDA for different lengths of time, and (ii) to document the repopulation of skin by the O. volvulus microfilariae following treatment, using 3 independent diagnostic techniques., Method: Identified microfilaridermic individuals were treated with ivermectin and re-examined after 1, 3, and 6 months using microscopy, actin real-time PCR (actin-qPCR) and O-150 LAMP assays. Susceptibility to ivermectin and trends in detecting reappearance of skin microfilariae were determined using three techniques. Microscopy was used as an imperfect gold standard to determine the performance of actin-qPCR and LAMP., Results: In Bafia with over 20 years of IVM-MDA, 11/51 (21.6%) direct observe treated microfilaridemic participants were still positive for skin microfilariae after 1 month. In Melong, with 10 years of IVM-MDA, 2/29 (6.9%) treated participants were still positive. The microfilarial density reduction per skin biopsy within one month following treatment was significantly lower in participants from Bafia. In both study sites, the molecular techniques detected higher proportions of infected individuals than microscopy at all monitoring time points. LAMP demonstrated the highest levels of sensitivity and real-time PCR was found to have the highest specificity., Conclusion: Patterns in skin mirofilariae clearance and repopulation were established. O. volvulus worms from Bafia with higher number of annual MDA displayed a lower clearance and higher repopulation rate after treatment with ivermectin. Molecular assays displayed higher sensitivity in monitoring O. volvulus microfilaridemia within six months following treatment.

Human landing collections (HLCs) have been the standard method for the collection of black flies that serve as vectors for Onchocerca volvulus , the causative agent of onchocerciasis or river blindness. However, HLCs are inefficient and may expose collectors to vector-borne pathogens. The Esperanza window trap (EWT) has been shown to be a potential alternative to HLCs for the collection of Simulium damnosum , the principal vector of O. volvulus in Africa. To improve the performance of the EWT, sweat from individuals highly attractive or less attractive to S. damnosum sensu stricto was examined by gas chromatography and mass spectroscopy. Twelve compounds were identified which were solely present or present in increased amounts in the sweat of the highly attractive individuals. Two of these compounds (naphthalene and tert-hexadecyl mercaptan) were found to be attractive to S. damnosum s.s. in behavioral assays. Traps baited with these compounds outperformed those baited with the current standard bait of worn socks. Using these newly identified compounds as baits will make the EWT more efficient in collecting vector black flies and may enhance the potential utility of the EWT as a local vector control measure.

Filarial nematodes can cause debilitating diseases in humans. They have complicated life cycles involving an insect vector and mammalian hosts, and they go through a number of developmental molts. While whole genome sequences of parasitic worms are now available, very little is known about transcription factor (TF) binding sites and their cognate transcription factors that play a role in regulating development. To address this gap, we developed a novel motif prediction pipeline, Emotif Alpha, that integrates ten different motif discovery algorithms, multiple statistical tests, and a comparative analysis of conserved elements between the filarial worms Brugia malayi and Onchocerca volvulus, and the free-living nematode Caenorhabditis elegans. We identified stage-specific TF binding motifs in B. malayi, with a particular focus on those potentially involved in the L3-L4 molt, a stage important for the establishment of infection in the mammalian host. Using an in vitro molting system, we tested and validated three of these motifs demonstrating the accuracy of the motif prediction pipeline., Competing Interests: The authors have declared that no competing interests exist.

Skin snip evaluation for onchocerciasis has insufficient sensitivity when skin microfilarial (mf) densities are low, such as following ivermectin treatment. Mf density is suitable for assessing microfilaricidal efficacy but only serves as an indirect indicator of macrofilaricidal activity. We assessed circulating nucleic acids from Onchocerca volvulus as an alternative to skin snips. We screened a plasma sample set of infected individuals followed up at four, 12 and 21 months after microfilaricidal (ivermectin, n = four), macrofilaricidal (doxycycline, n = nine), or combination treatment (n = five). Two parasite-derived miRNAs, cel-miR-71-5p and bma-lin-4, and O-150 repeat DNA were assessed. Highly abundant DNA repeat families identified in the O. volvulus genome were also evaluated. miRNAs were detected in two of 72 plasma samples (2.8%) and two of 47 samples (4.3%) with microfilaridermia using RT-qPCR. O-150 DNA was detected in eight (44.4%) baseline samples by qPCR and the number of positives declined post-treatment. One doxycycline-treated individual remained O-150 positive. However, only 11 (23.4%) samples with microfilaridermia were qPCR-positive. Analysis by qPCR showed novel DNA repeat families were comparatively less abundant than the O-150 repeat. Circulating parasite-derived nucleic acids are therefore insufficient as diagnostic tools or as biomarkers of treatment efficacy for O. volvulus.

Background: Onchocerciasis transmission across international borders is not uncommon, yet a coordinated cross border stops mass drug administration (MDA) decision has not been documented., Methods/principle Findings: The Galabat-Metema focus involves neighboring districts on the border between Sudan and Ethiopia. Mass drug administration (MDA) was provided once and subsequently twice per year in this focus, with twice-per-year beginning in Ethiopia's Metema subfocus in 2016 and in the Sudan's Galabat subfocus in 2008. Ov16 ELISA-based serosurveys were conducted in 6072 children under 10 years of age in the Metema subfocus in 2014, and 3931 in the Galabat in 2015. Between 2014 and 2016, a total of 27,583 vector Simulium damnosum flies from Metema and 9,148 flies from Galabat were tested by pool screen PCR for Onchocerca volvulus O-150 DNA. Only 8 children were Ov16 seropositive (all in the Metema subfocus); all were negative by skin snip PCR. The upper limit of the 95% confidence interval (UCL) for Ov16 seropositive was <0.1% for the overall focus and 0.14 positive fly heads per 2000 (UCL = 0.39/2000). However, an entomological 'hotspot' was detected on the Wudi Gemzu river in Metema district. The hotspot was confirmed when 4 more positive fly pools were found on repeat testing in 2017 (1.04 L3/2000 flies (UCL = 2.26/2000). Information exchange between the two countries led to stopping MDA in a coordinated fashion in 2018, with the exception of the hotspot at Wudi Gemzu, where MDA with ivermectin was increased to every three months to hasten interruption of transmission., Conclusion: Coordinated stop MDA decisions were made by Sudan and Ethiopia based on data satisfying the World Health Organization's criteria for interruption of onchocerciasis transmission. Definitions of entomological 'hotspots' and buffer zones around the focus are proposed., Competing Interests: The authors have declared that no competing interests exist.

Background: Onchocerciasis, or river blindness, has historically been an important cause of blindness, skin disease and economic disruption in Africa and the Americas. It is caused by the filarial parasite Onchocerca volvulus, which is transmitted by black flies in the genus Simulium. Over the past decade, several international programs have been formed to control, or more recently eliminate onchocerciasis, using mass drug administration (MDA) of ivermectin. However, in many areas of Africa (particularly those which are endemic for the eyeworm, Loa loa, or where vector densities are very high) ivermectin MDA alone will not be sufficient to achieve elimination. In these situations, additional interventions may be necessary., Methodology/principal Findings: The Esperanza Window trap (EWT), a simple trap originally developed to replace human landing collections for entomological surveillance of O. volvulus transmission was optimized, resulting in a 17-fold improvement in trap performance. The optimized trap was tested in trials in schools and in agricultural fields to determine if it could reduce vector biting locally. The traps resulted in a 90% reduction in biting in the school setting. In the field setting, results varied. In one location, the traps reduced biting by roughly 50%, while in a separate trial, the traps did not significantly reduce the biting rate. Examination of the two settings suggested that trap placement may be critical to their success., Conclusions/significance: These results suggest that the optimized EWT might be capable of reducing local vector black fly biting in areas commonly frequented by residents. Together with other recently developed methods of community directed vector control, the traps may augment ivermectin MDA, bringing the goal of onchocerciasis elimination within reach in much of Africa., Competing Interests: The authors have declared that no competing interests exist.

Background: The study of Onchocerca volvulus has been limited by its host range, with only humans and non-human primates shown to be susceptible to the full life cycle infection. Small animal models that support the development of adult parasites have not been identified., Methodology/principal Findings: We hypothesized that highly immunodeficient NSG mice would support the survival and maturation of O. volvulus and alteration of the host microenvironment through the addition of various human cells and tissues would further enhance the level of parasite maturation. NSG mice were humanized with: (1) umbilical cord derived CD34+ stem cells, (2) fetal derived liver, thymus and CD34+ stem cells or (3) primary human skeletal muscle cells. NSG and humanized NSG mice were infected with 100 O. volvulus infective larvae (L3) for 4 to 12 weeks. When necropsies of infected animals were performed, it was observed that parasites survived and developed throughout the infection time course. In each of the different humanized mouse models, worms matured from L3 to advanced fourth stage larvae, with both male and female organ development. In addition, worms increased in length by up to 4-fold. Serum and urine, collected from humanized mice for identification of potential biomarkers of infection, allowed for the identification of 10 O. volvulus-derived proteins found specifically in either the urine or the serum of the humanized O. volvulus-infected NSG mice., Conclusions/significance: The newly identified mouse models for onchocerciasis will enable the development of O. volvulus specific biomarkers, screening for new therapeutic approaches and potentially studying the human immune response to infection with O. volvulus., Competing Interests: The authors have declared that no competing interests exist.

Background: Massangam health district (HD), in the West Region of Cameroon, has received ivermectin mass drug administration (MDA) for 20 years, however there is evidence of continued high transmission of Onchocerca volvulus. In order to better understand the transmission dynamics in the HD and inform intervention strategies there is a need to delineate the boundaries of the suspected area of high transmission within the wider transmission zone., Methodology/principal Findings: Parasitological and entomological surveys were conducted to map out the breeding sites of Simulium damnosum and evaluate the prevalence of onchocerciasis in neighbouring communities, including Makouopsap sentinel community. Potential rapids were prospected for identification of S. damnosum larvae and black flies collected to determine infectivity rates. Adults were assessed for the presence of O. volvulus microfilariae through a skin snip biopsy and examined for the presence of nodules. Anti Ov-16 antibodies were tested for in children. Four perennial breeding sites were identified on the Rivers Mbam and Nja. Large number of flies were collected along the River Mbam, especially in the rainy season, with up to 955 flies per day, suggesting this river is a perennial source of black flies. A total of 0.8% of parous flies were infective across the study area. Parasitological studies provided evidence of high rates of infection in the sentinel community and three neighbouring communities, with 37.1% of adults microfilariae positive in Makouopsap. High Ov-16 seropositivity in children also provided evidence of recent on-going transmission. In comparison, communities sampled further away from the sentinel community and neighbouring breeding sites were much closer to reaching onchocerciasis elimination targets., Conclusions/significance: This study provides evidence of a particular geographic area of high transmission in an approximate 12 km range around the sentinel community of Makouopsap and the neighbouring breeding sites on the River Nja. To eliminate onchocerciasis by 2025, there is a need to explore alternative intervention strategies in this area of high transmission., Competing Interests: The authors have declared that no competing interests exist.

Background: A 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., Methods: Between 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)., Results: Onchocerciasis 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., Conclusions: This case control study confirms that O. volvulus is a risk factor for developing epilepsy in onchocerciasis endemic regions in the DRC.

Background: Onchocerciasis a neglected tropical disease that historically has been a major cause of morbidity and an obstacle to economic development in the developing world. It is caused by infection with Onchocerca volvulus, which is transmitted by black flies of the genus Simulium. The discovery of the potent effect of Mectizan (ivermectin) on O. volvulus microfilariae and the decision by its manufacturer to donate the drug for onchocerciasis spurred the implementation of international programs to control and, more recently, eliminate this scourge. These programs rely primarily on mass distribution of ivermectin (MDA) to the afflicted populations. However, MDA alone will not be sufficient to eliminate onchocerciasis where transmission is intense and where ivermectin MDA is precluded by co-endemicity with Loa loa. Vector control will likely be required as a supplemental intervention in these situations., Methodology/principal Findings: Because biting by the black fly vectors is often a major nuisance in onchocerciasis afflicted communities, we hypothesized that community members might be mobilized to clear the breeding sites of the vegetation that represents the primary black fly larvae attachment point. We evaluated the effect of such a community based "slash and clear" intervention in multiple communities in Northern Uganda. Slash and Clear resulted in 89-99% declines in vector biting rates. The effect lasted up to 120 days post intervention., Conclusions/significance: Slash and clear might represent an effective, inexpensive, community- based tool to supplement ivermectin distribution as a contributory method to eliminate onchocerciasis and prevent recrudescence., Competing Interests: The authors have declared that no competing interests exist.

Background: Onchocerciasis is found predominantly in Africa where large scale vector control started in 1974. Registration and donation of ivermectin by Merck & Co in 1987 enabled mass treatment with ivermectin in all endemic countries in Africa and the Americas. Although elimination of onchocerciasis with ivermectin was considered feasible only in the Americas, recently it has been shown possible in Africa too, necessitating fundamental changes in technical and operational approaches and procedures., Main Body: The American programme(OEPA) operating in onchocerciasis epidemiological settings similar to the mild end of the complex epidemiology of onchocerciasis in Africa, has succeeded in eliminating onchocerciasis from 4 of its 6 endemic countries. This was achieved through biannual mass treatment with ivermectin of 85% of the eligible population, and monitoring and evaluation using serological tests in children and entomological tests. The first African programme(OCP) had a head start of nearly two decades. It employed vector control and accumulated lots of knowledge on the dynamics of onchocerciasis elimination over a wide range of epidemiological settings in the vast expanse of its core area. OCP made extensive use of modelling and operationalised elimination indicators for entomological evaluation and epidemiological evaluation using skin snip procedures. The successor African programme(APOC) employed mainly ivermectin treatment. Initially its objective was to control onchocerciasis as a public health problem but that objective was later expanded to include the elimination of onchocerciasis where feasible. Building on the experience with onchocerciasis elimination of the OCP, APOC has leveraged OCP's vast modelling experience and has developed operational procedures and indicators for evaluating progress towards elimination and stopping ivermectin mass treatment of onchocerciasis in the complex African setting., Conclusions: Following the closure of APOC in 2015, implementation of onchocerciasis elimination in Africa appears to overlook all the experience that has been accumulated by the African programmes. It is employing predominantly American processes that were developed in a dissimilar setting from the complex African onchocerciasis setting. This is impeding progress towards decisions to stop intervention in many areas that have reached the elimination point. This article summarizes lessons learned in Africa and their importance for achieving elimination in Africa by 2025.

Background: Epilepsy is a neurological disorder with a multitude of underlying causes, which may include infection with Onchocerca volvulus, the parasitic worm that causes human onchocerciasis. A survey carried out in 1989 revealed a high prevalence of epilepsy (1.02% overall, ranging from 0.51 to 3.71% in ten villages) in the Mahenge area of Ulanga district, an onchocerciasis endemic region in south eastern Tanzania. This study aimed to determine the prevalence and incidence of epilepsy following 20 years of onchocerciasis control through annual community directed treatment with ivermectin (CDTI)., Methods: The study was conducted in January 2017 in two suburban and two rural villages in the Mahenge area. Door-to-door household visits were carried out by trained community health workers and data assistants to screen for persons suspected of having epilepsy, using a standardised questionnaire. Persons with suspected epilepsy were then interviewed and examined by a neurologist for case verification. Onchocerciasis associated epilepsy was defined as epilepsy without an obvious cause, with an onset of seizures between the ages of 3-18 years in previously healthy children. In each village, fifty males aged ≥20 years were tested for onchocerciasis antibodies using an OV16 rapid test and were examined for presence of onchocerciasis nodules. Children aged 6-10 years were also tested using OV16 tests., Results: 5117 individuals (median age 18.5 years, 53.2% female) from 1168 households were screened. 244 (4.8%) were suspected of having epilepsy and invited for neurological assessment. Prevalence of epilepsy was 2.5%, with the rural villages having the highest rate (3.5% vs 1.5%), P < 0.001. Overall incidence of epilepsy was 111 cases (95% CI: 73-161) per 100 000 person-years, while that of onchocerciasis associated epilepsy was 131 (95% CI: 70-223). Prevalence of OV16 antibodies in adult males and among children 6-10 years old was higher in rural villages than in suburban villages (76.5% vs 50.6, and 42.6% vs 4.7% respectively), (P < 0.001), while overall prevalence of onchocerciasis nodules was 1.8%., Conclusions: This survey revealed a high prevalence and incidence of epilepsy in two rural onchocerciasis endemic villages in the Mahenge area. Despite 20 years of CDTI, a high prevalence of OV16 antibodies in children aged 6-10 years suggests on-going O. volvulus transmission. Reasons for the persistence of on-going parasite transmission in the Mahenge area need to be investigated.

Background: Onchocerciasis is endemic in 12 of the 14 health districts of Sierra Leone. Good treatment coverage of community-directed treatment with ivermectin was achieved between 2005 and 2009 after the 11-year civil conflict. Sentinel site surveys were conducted in 2010 to evaluate the impact of five annual rounds of ivermectin distribution., Methods: In total, 39 sentinel villages from hyper- and meso-endemic areas across the 12 endemic districts were surveyed using skin snips in 2010. Results were analyzed and compared with the baseline data from the same 39 villages., Results: The average microfilaridermia (MF) prevalence across 39 sentinel villages was 53.10% at baseline. The MF prevalence was higher in older age groups, with the lowest in the age group of 1-9 years (11.00%) and the highest in the age group of 40-49 years (82.31%). Overall mean MF density among the positives was 28.87 microfilariae (mf)/snip, increasing with age with the lowest in the age group of 1-9 years and the highest in the age group of 40-49 years. Males had higher MF prevalence and density than females. In 2010 after five rounds of mass drug administration, the overall MF prevalence decreased by 60.26% from 53.10% to 21.10%; the overall mean MF density among the positives decreased by 71.29% from 28.87 mf/snip to 8.29 mf/snip; and the overall mean MF density among all persons examined decreased by 88.58% from 15.33 mf/snip to 1.75 mf/snip. Ten of 12 endemic districts had > 50% reduction in MF prevalence. Eleven of 12 districts had ≥50% reduction in mean MF density among the positives., Conclusions: A significant reduction of onchocerciasis MF prevalence and mean density was recorded in all 12 districts of Sierra Leone after five annual MDAs with effective treatment coverage. The results suggested that the onchocerciasis elimination programme in Sierra Leone was on course to reach the objective of eliminating onchocerciasis in the country by the year 2025. Annual MDA with ivermectin should continue in all 12 districts and further evaluations are needed across the country to assist the NTDP with programme decision making.

Background: Mass drug administration (MDA) with ivermectin is the cornerstone of efforts to eliminate human onchocerciasis by 2020 or 2025. The feasibility of elimination crucially depends on the effects of multiple ivermectin doses on Onchocerca volvulus. A single ivermectin (standard) dose clears the skin-dwelling microfilarial progeny of adult worms (macrofilariae) and temporarily impedes the release of such progeny by female macrofilariae, but a macrofilaricidal effect has been deemed minimal. Multiple doses of ivermectin may cumulatively and permanently reduce the fertility and shorten the lifespan of adult females. However, rigorous quantification of these effects necessitates interrogating longitudinal data on macrofilariae with suitably powerful analytical techniques., Methods: Using a novel mathematical modeling approach, we analyzed, at an individual participant level, longitudinal data on viability and fertility of female worms from the single most comprehensive multiple-dose clinical trial of ivermectin, comparing 3-monthly with annual treatments administered for 3 years in Cameroon., Results: Multiple doses of ivermectin have a partial macrofilaricidal and a modest permanent sterilizing effect after 4 or more consecutive treatments, even at routine MDA doses (150 µg/kg) and frequencies (annual). The life expectancy of adult O. volvulus is reduced by approximately 50% and 70% after 3 years of annual or 3-monthly (quarterly) exposures to ivermectin., Conclusions: Our quantification of macrofilaricidal and sterilizing effects of ivermectin should be incorporated into transmission models to inform onchocerciasis elimination efforts in Africa and residual foci in Latin America. It also provides a framework to assess macrofilaricidal candidate drugs currently under development., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.)

Entomological measures of transmission are important metrics specified by the World Health Organization to document the suppression and interruption of transmission of Onchocerca volvulus , the causative agent of onchocerciasis. These metrics require testing of large numbers of vector black flies. Black fly collection has relied on human landing collections, which are inefficient and potentially hazardous. As the focus of the international community has shifted from onchocerciasis control to elimination, replacement of human landing collections has become a priority. The Esperanza window trap (EWT) has shown promise as an alternative method for collection of Simulium damnosum s.l., the primary vector of O. volvulus in Africa. Here, we report the results of a community-based trial of the EWT in northern Uganda. Traps operated by residents were compared with human landing collections in two communities over 5 months. Three traps, when operated by a single village resident, collected over four times as many S. damnosum as did the two-men collection team. No significant differences were noted among the bait formulations. The results suggest that EWTs may be effectively operated by community residents and that the trap represents a viable alternative to human landing collections for entomological surveillance of O. volvulus transmission.

Lymphatic filariasis (LF) and onchocerciasis are priority neglected tropical diseases targeted for elimination. The only safe drug treatment with substantial curative activity against the filarial nematodes responsible for LF (Brugia malayi, Wuchereria bancrofti) or onchocerciasis (Onchocerca volvulus) is doxycycline. The target of doxycycline is the essential endosymbiont, Wolbachia. Four to six weeks doxycycline therapy achieves >90% depletion of Wolbachia in worm tissues leading to blockade of embryogenesis, adult sterility and premature death 18-24 months post-treatment. Long treatment length and contraindications in children and pregnancy are obstacles to implementing doxycycline as a public health strategy. Here we determine, via preclinical infection models of Brugia malayi or Onchocerca ochengi that elevated exposures of orally-administered rifampicin can lead to Wolbachia depletions from filariae more rapidly than those achieved by doxycycline. Dose escalation of rifampicin achieves >90% Wolbachia depletion in time periods of 7 days in B. malayi and 14 days in O. ochengi. Using pharmacokinetic-pharmacodynamic modelling and mouse-human bridging analysis, we conclude that clinically relevant dose elevations of rifampicin, which have recently been determined as safe in humans, could be administered as short courses to filariasis target populations with potential to reduce anti-Wolbachia curative therapy times to between one and two weeks.

Nodding syndrome is an epileptic disorder of unknown etiology that occurs in children in East Africa. There is an epidemiological association with Onchocerca volvulus , the parasitic worm that causes onchocerciasis (river blindness), but there is limited evidence that the parasite itself is neuroinvasive. We hypothesized that nodding syndrome may be an autoimmune-mediated disease. Using protein chip methodology, we detected autoantibodies to leiomodin-1 more abundantly in patients with nodding syndrome compared to unaffected controls from the same village. Leiomodin-1 autoantibodies were found in both the sera and cerebrospinal fluid of patients with nodding syndrome. Leiomodin-1 was found to be expressed in mature and developing human neurons in vitro and was localized in mouse brain to the CA3 region of the hippocampus, Purkinje cells in the cerebellum, and cortical neurons, structures that also appear to be affected in patients with nodding syndrome. Antibodies targeting leiomodin-1 were neurotoxic in vitro, and leiomodin-1 antibodies purified from patients with nodding syndrome were cross-reactive with O. volvulus antigens. This study provides initial evidence supporting the hypothesis that nodding syndrome is an autoimmune epileptic disorder caused by molecular mimicry with O. volvulus antigens and suggests that patients may benefit from immunomodulatory therapies., (Copyright © 2017, American Association for the Advancement of Science.)

The search for new macrofilaricidal drugs against onchocerciasis that can be administered in shorter regimens than required for doxycycline (DOX, 200mg/d given for 4-6 weeks), identified minocycline (MIN) with superior efficacy to DOX. Further reduction in the treatment regimen may be achieved with co-administration with standard anti-filarial drugs. Therefore a randomized, open-label, pilot trial was carried out in an area in Ghana endemic for onchocerciasis, comprising 5 different regimens: the standard regimen DOX 200mg/d for 4 weeks (DOX 4w, N = 33), the experimental regimens MIN 200mg/d for 3 weeks (MIN 3w; N = 30), DOX 200mg/d for 3 weeks plus albendazole (ALB) 800mg/d for 3 days (DOX 3w + ALB 3d, N = 32), DOX 200mg/d for 3 weeks (DOX 3w, N = 31) and ALB 800mg for 3 days (ALB 3d, N = 30). Out of 158 randomized participants, 116 (74.4%) were present for the follow-up at 6 months of whom 99 participants (63.5%) followed the treatment per protocol and underwent surgery. Histological analysis of the adult worms in the extirpated nodules revealed absence of Wolbachia in 98.8% (DOX 4w), 81.4% (DOX 3w + ALB 3d), 72.7% (MIN 3w), 64.1% (DOX 3w) and 35.2% (ALB 3d) of the female worms. All 4 treatment regimens showed superiority to ALB 3d (p < 0.001, p < 0.001, p = 0.002, p = 0.008, respectively), which was confirmed by real-time PCR. Additionally, DOX 4w showed superiority to all other treatment arms. Furthermore DOX 4w and DOX 3w + ALB 3d showed a higher amount of female worms with degenerated embryogenesis compared to ALB 3d (p = 0.028, p = 0.042, respectively). These results confirm earlier studies that DOX 4w is sufficient for Wolbachia depletion and the desired parasitological effects. The data further suggest that there is an additive effect of ALB (3 days) on top of that of DOX alone, and that MIN shows a trend for stronger potency than DOX. These latter two results are preliminary and need confirmation in a fully randomized controlled phase 2 trial., Trial Registration: ClinicalTrials.gov #06010453., Competing Interests: The author has declared that no competing interests exist.

Background: Vector-biting behaviour is important for vector-borne disease (VBD) epidemiology. The proportion of blood meals taken on humans (the human blood index, HBI), is a component of the biting rate per vector on humans in VBD transmission models. Humans are the definitive host of Onchocerca volvulus, but the simuliid vectors feed on a range of animals and HBI is a key indicator of the potential for human onchocerciasis transmission. Ghana has a diversity of Simulium damnosum complex members, which are likely to vary in their HBIs, an important consideration for parameterization of onchocerciasis control and elimination models., Methods: Host-seeking and ovipositing S. damnosum (sensu lato) (s.l.) were collected from seven villages in four Ghanaian regions. Taxa were morphologically and molecularly identified. Blood meals from individually stored blackfly abdomens were used for DNA profiling, to identify previous host choice. Household, domestic animal, wild mammal and bird surveys were performed to estimate the density and diversity of potential blood hosts of blackflies., Results: A total of 11,107 abdomens of simuliid females (which would have obtained blood meal(s) previously) were tested, with blood meals successfully amplified in 3,772 (34 %). A single-host species was identified in 2,857 (75.7 %) of the blood meals, of which 2,162 (75.7 %) were human. Simulium soubrense Beffa form, S. squamosum C and S. sanctipauli Pra form were the most anthropophagic (HBI = 0.92, 0.86 and 0.70, respectively); S. squamosum E, S. yahense and S. damnosum (sensu stricto) (s.s.)/S. sirbanum were the most zoophagic (HBI = 0.44, 0.53 and 0.63, respectively). The degree of anthropophagy decreased (but not statistically significantly) with increasing ratio of non-human/human blood hosts. Vector to human ratios ranged from 139 to 1,198 blackflies/person., Conclusions: DNA profiling can successfully identify blood meals from host-seeking and ovipositing blackflies. Host choice varies according to sibling species, season and capture site/method. There was no evidence that HBI is vector and/or host density dependent. Transmission breakpoints will vary among locations due to differing cytospecies compositions and vector abundances.

It was not until early 1990s that, when the Imaramagambo focus of southwest Uganda was mapped, mass treatment with a single annual dose of ivermectin for onchocerciaisis control commenced. However, comprehensive investigations on its transmission were launched after a nationwide policy for onchocerciasis elimination in 2007. Entomological surveys throughout the focus from 2007 to 2015 have yielded few or no freshwater crabs (Potamonautes aloysiisabaudiae), which serve as the obligate phoretic host of the larvae and pupae of the vector Simulium neavei No S. neavei flies have been observed or collected since 2007. Skin snips (microscopy) from 294 individuals in 2008 were negative for skin microfilariae, and of the 462 persons analyzed by polymerase chain reaction skin snip poolscreen in 2009, only five (1.08%) persons were indicated as infected with onchocerciasis. All five of the positive persons were at least 40 years old. Serosurvey results showed negative exposure among 3,332 children in 2012 and 3,108 children in 2015. Both were within the upper bound of the 95% confidence interval of the prevalence estimate of 0.06%, which confirmed the elimination of onchocerciasis. Treatment coverage in Imaramagambo was generally poor, and transmission interruption of onchocerciasis could not be attributed solely to annual mass treatment with ivermectin. There was sufficient evidence to believe that the possible disappearance of the S. neavei flies, presumed to have been the main vector, may have hastened the demise of onchocerciasis in this focus., (© The American Society of Tropical Medicine and Hygiene.)

Background: The reason for the high prevalence of epilepsy in onchocerciasis endemic areas remains unknown. The aim of this study was to detect risk factors associated with epilepsy in a region endemic for onchocerciasis., Methods: In June 2014, a case-control study was performed in Titule, Bas-Uélé Province in the Democratic Republic of the Congo. Individuals with unprovoked convulsive epilepsy of unknown aetiology were enrolled as cases (n=59). Healthy members of families without cases of epilepsy in the same village were recruited as controls (n=61). A multivariate binomial logistic regression analysis was performed to identify potential risk factors associated with epilepsy. To evaluate the potential protective effect of ivermectin treatment on the development of epilepsy, a nested age-matched case-control study was performed including only those who were eligible for ivermectin treatment in the year before they developed epilepsy., Results: Suspected onchocerciasis skin lesions were more often present in cases than in controls: 12/41 (29%) vs. 1/56 (2%), respectively (odds ratio (OR) 20.26, 95% confidence interval (CI) 2.42-170; p<0.01). Ivermectin had been taken 7 months earlier in 29/59 (49%) cases and 29/61 (48%) controls. Onchocerca volvulus (OV) DNA was detected by PCR in skin snips in 26/34 cases (76%) and 10/14 controls (71%) (p=0.7), and there was presence of OV IgG4 antibodies in 35/48 (73%) cases and 15/18 (83%) controls (p=0.5). OV DNA was not detected in the cerebrospinal fluid of cases (controls not tested). Both cases and controls reported frequent bites by blackflies (Diptera, Simuliidae). Bathing daily as opposed to less often (OR 16.7, 95% CI 2.2-125.8; p<0.01), bathing between 11 a.m. and 4 p.m. (OR 12.7, 95% CI 1.6-103.7; p=0.02), and washing clothes between 11 a.m. and 4 p.m. (OR 10.9, 95% CI 1.5-77.3; p=0.02) were all independently associated with epilepsy. Blood screening by specific PCR tests for Toxoplasma and Wuchereria bancrofti was negative in all cases and controls. A Loa loa infestation was found in only one case and one control by PCR and Giemsa smear. Antibodies to Taenia solium, Toxocara, and Trypanosoma sp were not detected in any of the participants. In an age-matched case-control analysis, 16/18 (89%) cases had not taken ivermectin the year before they developed epilepsy, compared to 7/18 (39%) controls that same year (p=0.002)., Conclusions: These data suggest that frequent activities at rivers known to be blackfly breeding sites and a historical lack of ivermectin treatment were risk factors for epilepsy in this onchocerciasis endemic area., (Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Onchocerciasis or "river blindness" is a chronic parasitic neglected tropical disease which is endemic both in mainland and insular Equatorial Guinea. We aim to estimate the current epidemiological situation of onchocerciasis in Bioko Island after vector elimination in 2005 and more than sixteen years of Community Directed Treatment with Ivermectin (CDTI) by using molecular and serological approaches for onchocerciasis diagnosis. A community-based cross-sectional study was carried out in Bioko Island from mid-January to mid-February 2014. A total of 544 study participants were recruited. A complete dermatological examination was performed and three skin snips were performed in every participant for parasitological and molecular assessments. Blood spots were also taken for determination of Ov16 IgG4 antibodies trough an "in-house" ELISA assay. Overall, we found 15 out of 522 individuals suffering any onchocerciasis specific cutaneous lesions and 16 out of 528 (3.0%) with onchocercal nodules in the skin. Nodules were significantly associated with age, being more common in subjects older than 10 years than in younger people (3.9% vs. 0%, p = 0.029). Regarding the onchocerciasis laboratory assessment, no positive parasitological test for microfilaria detection was found in the skin snips. The calculated seroprevalence through IgG4 serology was 7.9%. No children less than 10 years old were found to be positive for this test. Only one case was positive for Onchocerca volvulus (O. volvulus) after skin PCR. The present study points out that the on-going mass ivermectin treatment has been effective in reducing the prevalence of onchocerciasis and corroborates the interruption of transmission in Bioko Island. To our knowledge, this is the first time that accurate information through molecular and serological techniques is generated to estimate the onchocerciasis prevalence in this zone. Sustained support from the national program and appropriate communication and health education strategies to reinforce participation in CDTI activities are essential to ensure progress towards onchocerciasis elimination in the country.

Background: Onchocerciasis is one of the most important public health problems over large areas of tropical Africa countries including Ethiopia. The African Program for Onchocerciasis Control (APOC) has been working with ultimate goal of reducing the public health and socio-economic problems of onchocerciasis through administration of the tablet for continuous 12-15 years using the strategy of yearly community-directed treatment with ivermectin (CDTI) in endemic areas of Africa to kill the microfilariae that invade the eyes and are present in the skin to be transported to another victim by the black fly. The objective of this study was to assess knowledge, attitude and practice of community drug distributors (CDDs) towards onchocerciasis and CDTI in Quara district., Result: Of all the study participating CDD 11.4% (9/79) said that they knew about the etiology of the disease, 35.4% (28/79) had good level of knowledge, 19 (24.1%) had good level of positive attitude and 18 (22.8%) had good level of positive practice about onchocerciasis. Similarly, 45.6% (36/79), 81.0% (64/79) and 29.1% (23/79) had good level of knowledge, attitude and practice about CDTIP, respectively. Being a female CDD (adjusted OR 7.246, P = 0.035, 95% CI 1.147, 45.455) and being older than 35 years (adjusted OR 8.435, P = 0.001, 95% CI 4.53, 9.003) were significantly associated with the likelihood of having good level of knowledge about the disease., Conclusion: Although onchocerciasis is endemic in Quara district, large proportion of the CDDs had misconceptions about its causation, transmission and prevention. Therefore, CDTIP for onchocerciasis control need to be supported by proper and continuous training, and health education about different aspects of the disease.

Background: The abundance of onchocerciasis vectors affects the epidemiology of disease in Sudan, therefore, studies of vector dynamics are crucial for onchocerciasis control/elimination programs. This study aims to compare the relative abundance, monthly biting-rates (MBR) and hourly-based distribution of onchocerciasis vectors in Abu-Hamed and Galabat foci. These seasonally-based factors can be used to structure vector control efforts to reduce fly-biting rates as a component of onchocerciasis elimination programs., Methods: A cross-sectional study was conducted in four endemic villages in Abu-Hamed and Galabat foci during two non-consecutive years (2007-2008 and 2009-2010). Both adults and aquatic stages of the potential onchocerciasis vector Simulium damnosum sensu lato were collected following standard procedures during wet and dry seasons. Adult flies were collected using human landing capture for 5 days/month. The data was recorded on handheld data collection sheets to calculate the relative abundance, MBR, and hourly-based distribution associated with climatic factors. The data analysis was carried out using ANOVA and Spearman rank correlation tests., Results: Data on vector surveillance revealed higher relative abundance of S. damnosum s.l. in Abu- Hamed (39,934 flies) than Galabat (8,202 flies). In Abu-Hamed, vector populations increased in January-April then declined in June-July until they disappeared in August-October. Highest black fly density and MBR were found in March 2007 (N = 9,444, MBR = 58,552.8 bites/person/month), and March 2010 (N = 2,603, MBR = 16,138.6 bites/person/month) while none of flies were collected in August-October (MBR = 0 bites/person/month). In Galabat, vectors increased in September-December, then decreased in February-June. The highest vector density and MBR were recorded in September 2007 (N = 1,138, MBR = 6,828 bites/person/month) and September 2010 (N = 1,163, MBR = 6,978 bites/person/month), whereas, none appeared in collection from April to June. There was a significant difference in mean monthly density of S. damnosum s.l. across the two foci in 2007-2008 (df = 3, F = 3.91, P = 0.011). Minimum temperature showed significant correlation with adult flies counts in four areas sampled; the adult counts were increased in Nady village (rs = 0.799) and were decreased in Kalasecal (rs = -0.676), Gumaiza (rs = -0.585), and Hilat Khateir (rs = -0.496). Maximum temperature showed positive correlation with black fly counts only in Galabat focus. Precipitation was significantly correlated with adult flies counts in Nady village, Abu-Hamed, but no significance was found in the rest of the sampled villages in both foci. Hourly-based distribution of black flies showed a unimodal pattern in Abu-Hamed with one peak (10:00-18:00), while a bimodal pattern with two peaks (07:00-10:00) and (14:00-18:00) was exhibited in Galabat., Conclusion: Transmission of onchocerciasis in both foci showed marked differences in seasonality, which may be attributed to ecology, microclimate and proximity of breeding sites to collection sites. The seasonal shifts between the two foci might be related to variations in climate zones. This information on black fly vector seasonality, ecology, distribution and biting activity has obvious implications in monitoring transmission levels to guide the national and regional onchocerciasis elimination programs in Sudan.

Background: Recent reports of transmission interruption of Onchocerca volvulus, the causing agent of river blindness, in former endemic foci in the Americas, and more recently in West and East Africa, raise the question whether elimination of this debilitating disease is underway after long-term treatment of the population at risk with ivermectin. The situation in Central Africa has not yet been clearly assessed., Methods and Findings: Entomologic data from two former endemic river basins in North Cameroon were generated over a period of 43 and 48 months to follow-up transmission levels in areas under prolonged ivermectin control. Moreover, epidemiologic parameters of animal-borne Onchocerca spp. transmitted by the same local black fly vectors of the Simulium damnosum complex were recorded and their impact on O. volvulus transmission success evaluated. With mitochondrial DNA markers we unambiguously confirmed the presence of infective O. volvulus larvae in vectors from the Sudan savannah region (mean Annual Transmission Potential 2009-2012: 98, range 47-221), but not from the Adamawa highland region. Transmission rates of O. ochengi, a parasite of Zebu cattle, were high in both foci., Conclusions/significance: The high cattle livestock density in conjunction with the high transmission rates of the bovine filaria O. ochengi prevents the transmission of O. volvulus on the Adamawa plateau, whereas transmission in a former hyperendemic focus was markedly reduced, but not completely interrupted after 25 years of ivermectin control. This study may be helpful to gauge the impact of the presence of animal-filariae for O. volvulus transmission in terms of the growing human and livestock populations in sub-Saharan countries.

Background: The World Health Organization (WHO) has set goals for onchocerciasis elimination in Latin America by 2015. Most of the six previously endemic countries are attaining this goal by implementing twice a year (and in some foci, quarterly) mass ivermectin (Mectizan®) distribution. Elimination of transmission has been verified in Colombia, Ecuador and Mexico. Challenges remain in the Amazonian focus straddling Venezuela and Brazil, where the disease affects the hard-to-reach Yanomami indigenous population. We provide evidence of suppression of Onchocerca volvulus transmission by Simulium guianense s.l. in 16 previously hyperendemic Yanomami communities in southern Venezuela after 15 years of 6-monthly and 5 years of 3-monthly mass ivermectin treatment., Methods: Baseline and monitoring and evaluation parasitological, ophthalmological, entomological and serological surveys were conducted in selected sentinel and extra-sentinel communities of the focus throughout the implementation of the programme., Results: From 2010 to 2012-2015, clinico-parasitological surveys indicate a substantial decrease in skin microfilarial prevalence and intensity of infection; accompanied by no evidence (or very low prevalence and intensity) of ocular microfilariae in the examined population. Of a total of 51,341 S. guianense flies tested by PCR none had L3 infection (heads only). Prevalence of infective flies and seasonal transmission potentials in 2012-2013 were, respectively, under 1% and 20 L3/person/transmission season. Serology in children aged 1-10 years demonstrated that although 26 out of 396 (7%) individuals still had Ov-16 antibodies, only 4/218 (2%) seropositives were aged 1-5 years., Conclusions: We report evidence of recent transmission and morbidity suppression in some communities of the focus representing 75% of the Yanomami population and 70% of all known communities. We conclude that onchocerciasis transmission could be feasibly interrupted in the Venezuelan Amazonian focus.

Background: The initial endemicity (pre-control prevalence) of onchocerciasis has been shown to be an important determinant of the feasibility of elimination by mass ivermectin distribution. We present the first geostatistical map of microfilarial prevalence in the former Onchocerciasis Control Programme in West Africa (OCP) before commencement of antivectorial and antiparasitic interventions., Methods and Findings: Pre-control microfilarial prevalence data from 737 villages across the 11 constituent countries in the OCP epidemiological database were used as ground-truth data. These 737 data points, plus a set of statistically selected environmental covariates, were used in a Bayesian model-based geostatistical (B-MBG) approach to generate a continuous surface (at pixel resolution of 5 km x 5km) of microfilarial prevalence in West Africa prior to the commencement of the OCP. Uncertainty in model predictions was measured using a suite of validation statistics, performed on bootstrap samples of held-out validation data. The mean Pearson's correlation between observed and estimated prevalence at validation locations was 0.693; the mean prediction error (average difference between observed and estimated values) was 0.77%, and the mean absolute prediction error (average magnitude of difference between observed and estimated values) was 12.2%. Within OCP boundaries, 17.8 million people were deemed to have been at risk, 7.55 million to have been infected, and mean microfilarial prevalence to have been 45% (range: 2-90%) in 1975., Conclusions and Significance: This is the first map of initial onchocerciasis prevalence in West Africa using B-MBG. Important environmental predictors of infection prevalence were identified and used in a model out-performing those without spatial random effects or environmental covariates. Results may be compared with recent epidemiological mapping efforts to find areas of persisting transmission. These methods may be extended to areas where data are sparse, and may be used to help inform the feasibility of elimination with current and novel tools.

Human onchocerciasis (river blindness) is one of the few neglected tropical diseases (NTDs) whose control strategies have been informed by mathematical modelling. With the change in focus from elimination of the disease burden to elimination of Onchocerca volvulus, much remains to be done to refine, calibrate and validate existing models. Under the impetus of the NTD Modelling Consortium, the teams that developed EPIONCHO and ONCHOSIM have joined forces to compare and improve these frameworks to better assist ongoing elimination efforts. We review their current versions and describe how they are being used to address two key questions: (1) where can onchocerciasis be eliminated with current intervention strategies by 2020/2025? and (2) what alternative/complementary strategies could help to accelerate elimination where (1) cannot be achieved? The control and elimination of onchocerciasis from the African continent is at a crucial crossroad. The African Programme for Onchocerciasis Control closed at the end of 2015, and although a new platform for support and integration of NTD control has been launched, the disease will have to compete with a myriad of other national health priorities at a pivotal time in the road to elimination. However, never before had onchocerciasis control a better arsenal of intervention strategies as well as diagnostics. It is, therefore, timely to present two models of different geneses and modelling traditions as they come together to produce robust decision-support tools. We start by describing the structural and parametric assumptions of EPIONCHO and ONCHOSIM; we continue by summarizing the modelling of current treatment strategies with annual (or biannual) mass ivermectin distribution and introduce a number of alternative strategies, including other microfilaricidal therapies (such as moxidectin), macrofilaricidal (anti-wolbachial) treatments, focal vector control and the possibility of an onchocerciasis vaccine. We conclude by discussing challenges, opportunities and future directions., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Elimination of onchocerciasis in Africa is now regarded as an achievable goal in many areas. This makes monitoring changes in infection prevalence a key component of control programmes. Monitoring is currently based on determining the presence of O. volvulus microfilariae in skin snips, an invasive, labour-intensive method. The Onchocerciasis Control Programme (OCP) had established procedures to detect O. volvulus infections via the localized skin reaction induced by killing of microfilariae upon skin exposure to diethylcarbamazine via a patch (OCP-patch). Large scale OCP - patch use is difficult due to labour-intensive patch preparation. At the request of TDR, a manufacturer specialized in transdermal-delivery systems developed a ready-to-use diethylcarbamazine (DEC) containing patch (LTS-2 patch). To qualify this patch for large scale studies of its sensitivity and specificity, this study evaluated its ease of application, ability to detect infection and DEC exposure related adverse reactions compared to the OCP-patch in 30 infected individuals., Methods: Each participant with 0.2-36.8 O. volvulus microfilariae/mg skin received the OCP-patch and 4 days later the LTS-2 patch at the left and right iliac crest, respectively, for 24 h. Presence and characteristics of local skin reactions were assessed at patch removal and 6 h later. Skin reaction and Mazzotti reaction rates were compared with Fisher's exact and a paired t-test, respectively., Results: The LTS-2 patch could be applied within 10 s. Mild itching occurred at 63.3 % of OCP-patch (duration 8.9 ± 11.8 h) and 26.7 % of LTS-2 patch sites (duration 1.0 ± 2.5 h) and was the most frequent Mazzotti reaction. At patch removal after 24 h, a diagnostic local skin reaction was present under 90 % of OCP-patches and 83 % of LTS-2 patches; 6 h later, it was present at 93 % of OCP-patch and 100 % of LTS-2 patch sites., Conclusions: The data suggest that safety, tolerability and ability to detect infections of the LTS-2 patch are comparable to those of the OCP-patch. They qualify the LTS-2 patch for field studies to determine LTS-2 patch sensitivity, specificity and utility during large scale use and thus to inform use of the LTS-2 patch by onchocerciasis control programmes to determine prevalence of infection., Trial Registration: Current controlled Trials ISRCTN76875372 .

Background: Ivermectin (IVM) has been the drug of choice for the treatment of onchocerciasis. However, there have been reports of persistent microfilaridermia in individuals from an endemic area in Ghana after many rounds of IVM, raising concerns of suboptimal response or even the emergence of drug resistance. Because it is considered risky to continue relying only on IVM to combat this phenomenon, we assessed the effect of targeting the Onchocerca volvulus Wolbachia endosymbionts with doxycycline for these individuals with suboptimal response., Methods: One hundred sixty-seven patients, most of them with multiple rounds of IVM, were recruited in areas with IVM suboptimal response and treated with 100 mg/day doxycycline for 6 weeks. Three and 12 months after doxycycline treatment, patients took part in standard IVM treatment., Results: At 20 months after treatment, 80% of living female worms from the placebo group were Wolbachia positive, whereas only 5.1% in the doxycycline-treated group contained bacteria. Consistent with interruption of embryogenesis, none of the nodules removed from doxycycline-treated patients contained microfilariae, and 97% of those patients were without microfilaridermia, in contrast to placebo patients who remained at pretreatment levels (P < .001). Moreover, a significantly enhanced number of dead worms were observed after doxycycline., Conclusions: Targeting the Wolbachia in O. volvulus is effective in clearing microfilariae in the skin of onchocerciasis patients with persistent microfilaridermia and in enhanced killing of adult worms after repeated standard IVM treatment. Strategies can now be developed that include doxycycline to control onchocerciasis in areas where infections persist despite the frequent use of IVM., Clinical Trials Registration: ISRCTN 66649839., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.)

Background: Mexico is one of the six countries formerly endemic for onchocerciasis in Latin America. Transmission has been interrupted in the three endemic foci of that country and mass drug distribution has ceased. Three years after mass drug distribution ended, post-treatment surveillance (PTS) surveys were undertaken which employed entomological indicators to check for transmission recrudescence., Methodology/principal Findings: In-depth entomologic assessments were performed in 18 communities in the three endemic foci of Mexico. None of the 108,212 Simulium ochraceum s.l. collected from the three foci were found to contain parasite DNA when tested by polymerase chain reaction-enzyme-linked immunosorbent assay (PCR-ELISA), resulting in a maximum upper bound of the 95% confidence interval (95%-ULCI) of the infective rate in the vectors of 0.035/2,000 flies examined. This is an order of magnitude below the threshold of a 95%-ULCI of less than one infective fly per 2,000 flies tested, the current entomological criterion for interruption of transmission developed by the international community. The point estimate of seasonal transmission potential (STP) was zero, and the upper bound of the 95% confidence interval for the STP ranged from 1.2 to 1.7 L3/person/season in the different foci. This value is below all previous estimates for the minimum transmission potential required to maintain the parasite population., Conclusions/significance: The results from the in-depth entomological post treatment surveillance surveys strongly suggest that transmission has not resumed in the three foci of Mexico during the three years since the last distribution of ivermectin occurred; it was concluded that transmission remains undetectable without intervention, and Onchocerca volvulus has been eliminated from Mexico.

Development times of eggs, larvae and pupae of vectors of onchocerciasis (Simulium spp.) and of Onchocerca volvulus larvae within the adult females of the vectors decrease with increasing temperature. At and above 25°C, the parasite could reach its infective stage in less than 7 days when vectors could transmit after only two gonotrophic cycles. After incorporating exponential functions for vector development into a novel blackfly population model, it was predicted that fly numbers in Liberia and Ghana would peak at air temperatures of 29°C and 34°C, about 3°C and 7°C above current monthly averages, respectively; parous rates of forest flies (Liberia) would peak at 29°C and of savannah flies (Ghana) at 30°C. Small temperature increases (less than 2°C) might lead to changes in geographical distributions of different vector taxa. When the new model was linked to an existing framework for the population dynamics of onchocerciasis in humans and vectors, transmission rates and worm loads were projected to increase with temperature to at least 33°C. By contrast, analyses of field data on forest flies in Liberia and savannah flies in Ghana, in relation to regional climate change predictions, suggested, on the basis of simple regressions, that 13-41% decreases in fly numbers would be expected between the present and before 2040. Further research is needed to reconcile these conflicting conclusions.

Following studies on the transmission of Onchocerca volvulus (Leuckart) by Simulium sanctipauli Vajime & Dunbar (Diptera, Simuliidae) in Upper Denkyira District in Ghana in 2001 and 2002 (Kutin et al., Med Vet Ent 18:167-173, 2004), further assessments were carried out in 2006 and 2013/2014 to determine whether transmission parameters had changed since community-directed ivermectin treatment (CDTI) began in 1999. There were no marked changes of the transmission intensities in 2006. Only slight, but non-significant, reductions were observed in infection rates of parous flies with larval stages (L1-L3) of O. volvulus from 44.1 % (of 1672 parous flies) in 2001/2002 to 42.1 % (506) in 2006 and from 6.5 to 5.9 % of flies carrying infective larvae in their heads. This suggested that there was an ongoing transmission in the area and the parasite reservoir in the human population was still high. Unexpectedly, further assessments conducted in October 2013 and March and October 2014 revealed that the vector S. sanctipauli had apparently disappeared and transmission had ceased, probably as a result of intensified gold mining activities along the rivers Ofin and Pra. The water of both rivers was extremely turbid, heavily loaded with suspended solids, probably preventing the development of blackfly larvae. Some breeding and biting of Simulium yahense Vajime & Dunbar was observed in a small tributary of the Pra, the Okumayemfuo, which is not affected by gold mining. However, the infection rate of flies was low, only 3.7 % of 163 parous flies were infected with first stage (L1) larvae of O. volvulus.

Background: Ghana is renowned for its sibling species diversity of the Simulium damnosum complex, vectors of Onchocerca volvulus. Detailed entomological knowledge becomes a priority as onchocerciasis control policy has shifted from morbidity reduction to elimination of infection. To date, understanding of transmission dynamics of O. volvulus has been mainly based on S. damnosum sensu stricto (s.s.) data. We aim to elucidate bionomic features of vector species of importance for onchocerciasis elimination efforts., Methods: We collected S. damnosum sensu lato from seven villages in four Ghanaian regions between 2009 and 2011, using standard vector collection, and human- and cattle-baited tents. Taxa were identified using morphological and molecular techniques. Monthly biting rates (MBR), parous rates and monthly parous biting rates (MPBR) are reported by locality, season, trapping method and hour of collection for each species., Results: S. damnosum s.s./S. sirbanum were collected at Asubende and Agborlekame, both savannah villages. A range of species was caught in the Volta region (forest-savannah mosaic) and Gyankobaa (forest), with S. squamosum or S. sanctipauli being the predominant species, respectively. In Bosomase (southern forest region) only S. sanctipauli was collected in the 2009 wet season, but in the 2010 dry season S. yahense was also caught. MBRs ranged from 714 bites/person/month at Agborlekame (100% S. damnosum s.s./S. sirbanum) to 8,586 bites/person/month at Pillar 83/Djodji (98.5% S. squamosum). MBRs were higher in the wet season. In contrast, parous rates were higher in the dry season (41.8% vs. 18.4%), resulting in higher MPBRs in the dry season. Daily host-seeking activity of S. damnosum s.s./S. sirbanum was bimodal, whilst S. squamosum and S. sanctipauli had unimodal afternoon peaks., Conclusions: The bionomic differences between sibling species of the S. damnosum complex need to be taken into account when designing entomological monitoring protocols for interventions and parameterising mathematical models for onchocerciasis control and elimination.

The study determined that Simulium neavei-transmitted onchocerciasis in Mount Elgon onchocerciasis focus had been interrupted. Annual mass treatment with ivermectin changed to two times per year along with vector elimination in 2007. Then, baseline microfilaria (mf) prevalence data of 1994 in five sentinel communities were compared with follow-up data in 2005 and 2011. Blood spots from 3,051 children obtained in 2009 were analyzed for Onchocerca volvulus immunoglobulin G4 antibodies. Fresh water crab host captures and blackflies collected indicated their infestation with larval stages of S. neavei and presence or absence of the vector, respectively. Mf rates dropped from 62.2% to 0.5%, and 1 (0.03%) of 3,051 children was positive for O. volvulus antibodies. Crab infestation dropped from 41.9% in 2007 to 0%, and S. neavei biting reduced to zero. Both remained zero for the next 3 years, confirming interruption of onchocerciasis transmission, and interventions were halted., (© The American Society of Tropical Medicine and Hygiene.)