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

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

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

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

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

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

Servicio Autónomo Centro Amazónico de Investigación y Control de Enfermedades Tropicales Simón Bolívar (CAICET)

Ente adscrito al Ministerio del Poder Popular para la Salud cuya misión es desarrollar investigaciones en las diversas ramas de las ciencias biomédicas, ambientales y socioantropológicas de las enfermedades tropicales y sus consecuencias, para la producción de conocimientos, desarrollo de tecnologías y prácticas culturalmente aceptadas, prevención y control de enfermedades endémicas, así como la formación de recursos humanos bajo los principios de universalidad, equidad, solidaridad y respeto a la biodiversidad cultural y ambiental, con capacidad de elevar la calidad de vida de la población de la región sur del país, especialmente de las poblaciones indígenas

Impact assessment of onchocerciasis through lymphatic filariasis transmission assessment surveys using Ov-16 rapid diagnostic tests in Sierra Leone.

BACKGROUND: Onchocerciasis is endemic in 14 of Sierra Leone's 16 districts with high prevalence (47-88.5%) according to skin snips at baseline. After 11 rounds of mass treatment with ivermectin with good coverage, an impact assessment was conducted in 2017 to assess the progress towards eliminating onchocerciasis in the country. METHODS: A cluster survey was conducted, either integrated with lymphatic filariasis (LF) transmission assessment survey (TAS) or standalone with the LF TAS sampling strategy in 12 (now 14) endemic districts. Finger prick blood samples of randomly selected children in Grades 1-4 were tested in the field using SD Bioline Onchocerciasis IgG4 rapid tests. RESULTS: In total, 17,402 children aged 4-19 years in 177 schools were tested, and data from 17,364 children aged 4-14 years (14,230 children aged 5-9 years) were analyzed. Three hundred forty-six children were confirmed positive for Ov-16 IgG4 antibodies, a prevalence of 2.0% (95% CI 1.8-2.2%) in children aged 4-14 years with prevalence increasing with age. Prevalence in boys (2.4%; 95% CI 2.1-2.7%) was higher than in girls (1.6%; 95% CI 1.4-1.9%). There was a trend of continued reduction from baseline to 2010. Using data from children aged 5-9 years, overall prevalence was 1.7% (95% CI 1.5-1.9%). The site prevalence ranged from 0 to 33.3% (median prevalence = 0.0%): < 2% in 127 schools, 2 to < 5% in 34 schools and ≥ 5% in 16 schools. There was a significant difference in average prevalence between districts. Using spatial analysis, the Ov-16 IgG4 antibody prevalence was predicted to be < 2% in coastal areas and in large parts of Koinadugu, Bombali and Tonkolili Districts, while high prevalence (> 5%) was predicted in some focal areas, centered in Karene, Kailahun and Moyamba/Tonkolili. CONCLUSIONS: Low Ov-16 IgG4 antibody prevalence was shown in most areas across Sierra Leone. In particular, low seroprevalence in children aged 5-9 years suggests that the infection was reduced to a low level after 11 rounds of treatment intervention. Sierra Leone has made major progress towards elimination of onchocerciasis. However, attention must be paid to those high prevalence focal areas.

Onchocerca volvulus microfilariae in the anterior chambers of the eye and ocular adverse events after a single dose of 8 mg moxidectin or 150 µg/kg ivermectin: results of a randomized double-blind Phase 3 trial in the Democratic Republic of the Congo, Ghana and Liberia.

BACKGROUND: After ivermectin became available, diethylcarbamazine (DEC) use was discontinued because of severe adverse reactions, including ocular reactions, in individuals with high Onchocerca volvulus microfilaridermia (microfilariae/mg skin, SmfD). Assuming long-term ivermectin use led to < 5 SmfD with little or no eye involvement, DEC + ivermectin + albendazole treatment a few months after ivermectin was proposed. In 2018, the US FDA approved moxidectin for treatment of O. volvulus infection. The Phase 3 study evaluated SmfD, microfilariae in the anterior chamber (mfAC) and adverse events (AEs) in ivermectin-naïve individuals with ≥ 10 SmfD after 8 mg moxidectin (n = 978) or 150 µg/kg ivermectin (n = 494) treatment. METHODS: We analyzed the data from 1463 participants with both eyes evaluated using six (0, 1-5, 6-10, 11-20, 21-40, > 40) mfAC and three pre-treatment (< 20, 20 to < 50, ≥ 50) and post-treatment (0, > 0-5, > 5) SmfD categories. A linear mixed model evaluated factors and covariates impacting mfAC levels. Ocular AEs were summarized by type and start post-treatment. Logistic models evaluated factors and covariates impacting the risk for ocular AEs. RESULTS: Moxidectin and ivermectin had the same effect on mfAC levels. These increased from pre-treatment to Day 4 and Month 1 in 20% and 16% of participants, respectively. Six and 12 months post-treatment, mfAC were detected in ≈5% and ≈3% of participants, respectively. Ocular Mazzotti reactions occurred in 12.4% of moxidectin- and 10.2% of ivermectin-treated participants without difference in type or severity. The risk for ≥ 1 ocular Mazzotti reaction increased for women (OR 1.537, 95% CI 1.096-2.157) and with mfAC levels pre- and 4 days post-treatment (OR 0: > 10 mfAC 2.704, 95% CI 1.27-5.749 and 1.619, 95% CI 0.80-3.280, respectively). CONCLUSIONS: The impact of SmfD and mfAC levels before and early after treatment on ocular AEs needs to be better understood before making decisions on the risk-benefit of strategies including DEC. Such decisions should take into account interindividual variability in SmfD, mfAC levels and treatment response and risks to even a small percentage of individuals.

Community's knowledge, perceptions and preventive practices on Onchocerciasis in Jimma zone, Ethiopia, formative mixed study.

BACKGROUND: In Ethiopia, Onchocerciasis is a prevalent neglected tropical disease, currently targeted for elimination with mass drug administration and community behavioral changes towards sustained control and eventual elimination. This study aimed to elucidate the awareness, perceptions and practices of endemic communities in Jimma Zone, Ethiopia. METHODS AND MATERIALS: Community-based cross-sectional study triangulated with qualitative method was conducted from October-November, 2021. A multistage sampling was employed and data were collected using a pre-tested interviewer-administered structured questionnaire. Logistic regression was used to identify the predictors of comprehensive knowledge and preventive practice. Adjusted odds ratios were calculated at 95% confidence interval (CI) and considered significant with a p-value of <0.05. Kruskal-Whallis and Mann-whitney tests were used to compare median risk perception score by socio-demographic factors. Qualitative data were collected through focus group discussions and key informant interviews and transcribed verbatim. Then the data were coded, categorized, and themes were developed. RESULT: The overall prevalence of adequate comprehensive knowledge was 48.8% (95% CI: 44.9, 52.3), high risk perception was 18.7% (95%CI15.9, 21.4) and preventive practice was 46.9%(95%CI:(43.3,50.4). High risk perception[AOR = 1.95 95%CI: (1.32, 2.89] was statistically significant with comprehensive knowledge, likewise knowledge of mode of transmission [AOR = 2.64 95% CI: (1.44, 4.85)], knowledge of consequences [AOR = 2.12 95%CI: (1.21, 3.72)] and knowledge of preventive measures [AOR = 15.65,95%CI:(10.1, 24.2)] were statistically significant with preventive practice. The median risk perception was varied significantly between the groups by educational status, study district and age category. Qualitative evidence showed that there were great community knowledge gap about the disease. CONCLUSION: Community knowledge, perceptions, and practices are unacceptably low. Risk perception was significantly associated with comprehensive knowledge, likewise knowledge of mode of transmission, consequences and preventive measures were significantly associated with preventive practice. This implies knowledge is a key component of effective prevention strategies as it is a necessary condition for the behavior change.

Elimination of transmission of onchocerciasis (river blindness) with long-term ivermectin mass drug administration with or without vector control in sub-Saharan Africa: a systematic review and meta-analysis.

BACKGROUND: WHO has proposed elimination of transmission of onchocerciasis (river blindness) by 2030. More than 99% of cases of onchocerciasis are in sub-Saharan Africa. Vector control and mass drug administration of ivermectin have been the main interventions for many years, with varying success. We aimed to identify factors associated with elimination of onchocerciasis transmission in sub-Saharan Africa. METHODS: For this systematic review and meta-analysis we searched for published articles reporting epidemiological or entomological assessments of onchocerciasis transmission status in sub-Saharan Africa, with or without vector control. We searched MEDLINE, PubMed, Web of Science, Embase, Cochrane Central Register of Controlled Trials, African Index Medicus, and Google Scholar databases for all articles published from database inception to Aug 19, 2023, without language restrictions. The search terms used were "onchocerciasis" AND "ivermectin" AND "mass drug administration". The three inclusion criteria were (1) focus or foci located in Africa, (2) reporting of elimination of transmission or at least 10 years of ivermectin mass drug administration in the focus or foci, and (3) inclusion of at least one of the following assessments: microfilarial prevalence, nodule prevalence, Ov16 antibody seroprevalence, and blackfly infectivity prevalence. Epidemiological modelling studies and reviews were excluded. Four reviewers (NM, AJ, AM, and TNK) extracted data in duplicate from the full-text articles using a data extraction tool developed in Excel with columns recording the data of interest to be extracted, and a column where important comments for each study could be highlighted. We did not request any individual-level data from authors. Foci were classified as achieving elimination of transmission, being close to elimination of transmission, or with ongoing transmission. We used mixed-effects meta-regression models to identify factors associated with transmission status. This study is registered in PROSPERO, CRD42022338986. FINDINGS: Of 1525 articles screened after the removal of duplicates, 75 provided 282 records from 238 distinct foci in 19 (70%) of the 27 onchocerciasis-endemic countries in sub-Saharan Africa. Elimination of transmission was reported in 24 (9%) records, being close to elimination of transmission in 86 (30%) records, and ongoing transmission in 172 (61%) records. I2 was 83·3% (95% CI 79·7 to 86·3). Records reporting 10 or more years of continuous mass drug administration with 80% or more therapeutic coverage of the eligible population yielded significantly higher odds of achieving elimination of transmission (log-odds 8·5 [95% CI 3·5 to 13·5]) or elimination and being close to elimination of transmission (42·4 [18·7 to 66·1]) than those with no years achieving 80% coverage or more. Reporting 15-19 years of ivermectin mass drug administration (22·7 [17·2 to 28·2]) and biannual treatment (43·3 [27·2 to 59·3]) were positively associated with elimination and being close to elimination of transmission compared with less than 15 years and no biannual mass drug administration, respectively. Having had vector control without vector elimination (-42·8 [-59·1 to -26·5]) and baseline holoendemicity (-41·97 [-60·6 to -23·2]) were associated with increased risk of ongoing transmission compared with no vector control and hypoendemicity, respectively. Blackfly disappearance due to vector control or environmental change contributed to elimination of transmission. INTERPRETATION: Mass drug administration duration, frequency, and coverage; baseline endemicity; and vector elimination or disappearance are important determinants of elimination of onchocerciasis transmission in sub-Saharan Africa. Our findings underscore the importance of improving and sustaining high therapeutic coverage and increasing treatment frequency if countries are to achieve elimination of onchocerciasis transmission. FUNDING: The Bill & Melinda Gates Foundation and Neglected Tropical Diseases Modelling Consortium, UK Medical Research Council, and Global Health EDCTP3 Joint Undertaking. TRANSLATIONS: For the Swahili, French, Spanish and Portuguese translations of the abstract see Supplementary Materials section.

Impact of annual community-directed treatment with ivermectin on the incidence of epilepsy in Mvolo, a two-year prospective study.

OBJECTIVES: The potential impact of cumulative community-directed treatment with ivermectin (CDTI) on epilepsy epidemiology in Mvolo County, South Sudan, an onchocerciasis-endemic area with high epilepsy prevalence, was investigated. Annual CDTI was introduced in 2002 in Mvolo, with interruptions in 2016 and 2020. METHODS: Comprehensive house-to-house surveys in Mvolo (June 2020 and 2022) identified cases of epilepsy, including probable nodding syndrome (pNS). Community workers screened households in selected sites for suspected epilepsy, and medical doctors confirmed the diagnosis and determined the year of seizure onset. The incidence of epilepsy, including pNS, was analysed using 95% confidence intervals (CIs). Data on ivermectin intake and onchocerciasis-associated manifestations (itching and blindness) were collected. RESULTS: The surveys covered 15,755 (2020) and 15,092 (2022) individuals, identifying 809 (5.2%, 95% CI: 4.8-5.5%) and 672 (4.5%, 95% CI: 4.1-4.8%) epilepsy cases, respectively. Each survey reported that a third of the surveyed population experienced skin itching, and 3% were blind. Epilepsy incidence per 100,000 person-years gradually declined, from 326.5 (95% CI: 266.8-399.1) in 2013-2015 to 96.6 (95% CI: 65.5-141.7) in 2019-2021. Similarly, pNS incidence per 100,000 person-years decreased from 151.7 (95% CI: 112.7-203.4) to 27.0 (95% CI: 12.5-55.5). Coverage of CDTI was suboptimal, reaching only 64.0% of participants in 2019 and falling to 24.1% in 2021 following an interruption in 2020 due to COVID-19 restrictions. Additionally, while 99.4% of cases had active epilepsy in 2022, less than a quarter of these had access to antiseizure medication. CONCLUSIONS: The observed decrease in epilepsy incidence despite suboptimal CDTI coverage highlights the potential impact of onchocerciasis control efforts and underscores the need to strengthen these efforts in Mvolo County and across South Sudan. As a proactive measure, Mvolo and neighbouring counties are transitioning to biannual CDTI. Furthermore, the substantial epilepsy treatment gap in Mvolo should be addressed.

Control, elimination, and eradication efforts for neglected tropical diseases in the World Health Organization African region over the last 30 years: A scoping review.

OBJECTIVES: NTDs historically receive less attention than other diseases in the same regions. Recent gap analyses revealed notable shortcomings despite NTD elimination progress. This systematic scoping review was conducted to understand NTD control, elimination, and eradication efforts in the WHO African region over the last 30 years. METHODS: Peer-reviewed publications from PubMed, Web of Science, and Cochrane databases related to NTD control, elimination, and eradication in the WHO African Region from 1990 to 2022 were reviewed. Included articles were categorized based on NTD; study location, type, and period; and topic areas. Technical and guidance documents from WHO, UN, partner, and academic/research institutions were reviewed. Country-specific multi-year NTD master plans were documented. RESULTS: Four hundred eighty peer-reviewed articles, six Cochrane reviews, and 134 technical reports were included. MDA and non-interventional/survey-related studies were common topics. Lymphatic filariasis, trachoma, schistosomiasis, and onchocerciasis were the most frequently studied NTDs. Tanzania, Ethiopia, and Nigeria were the most represented countries; multi-country studies were limited. CONCLUSION: The review highlights progress made in NTD control, elimination, and eradication efforts in the WHO African Region and can inform national/regional strategies. Disease and geographical disparities were evident, warranting focus and research in certain countries. A standardized approach to NTD control programs is needed for sustained progress. FUNDING: There was no funding source for this study.

Mapping, Associated Factors, and Pathophysiology of Nodding Syndrome in Africa: A Systematic Review.

INTRODUCTION: Nodding syndrome (NS) remains a poorly understood disorder. For a long time, it has been thought to be restricted to East Africa; however, cases in Central Africa have been increasing over time. The objective of this systematic review (SR) was to provide a summary of the state of knowledge on NS to date. METHODS: All original articles published on NS up to November 2021 were searched in four major databases and in the gray literature. Commentaries, editorials, book chapters, books, conference paper, qualitative studies that mentioned NS cases were also included. Data retrieved included study location (with GPS coordinates searched), year of study and publication, population characteristics, definition and diagnosis of NS, associated factors, and treatment if applicable. A meta-analysis of associated factors was performed where possible, and results were presented as odds ratios (ORs) and visualized as forest plots. Geographic information systems were used for cartographic representations. The quality of the articles included was assessed. RESULTS: Of the 876 articles initially identified, 67 (corresponding to 59 studies) were included in the SR. NS is only present in Central and East Africa. Interestingly, there were reports of NS in Central Africa prior to 2010, earlier than previously thought. The way NS diagnosis was established varies according to studies, and the 2012 WHO classification was used in only 60% of the studies. Approximately 11% of the articles did not meet the quality requirements set for this review. In our meta-analysis, the main factor associated with NS was onchocerciasis (OR = 8.8 [4.8, 15.9]). However, the pathophysiology of the disease remains poorly understood. The lack of common anti-epileptic drugs is a significant barrier to the management of head nodding and associated epileptic seizures. DISCUSSION/CONCLUSION: The lack of an operational definition of NS is an obstacle to its diagnosis and, thus, to its appropriate treatment. Indeed, diagnostic difficulties might have led to false positives and false negatives which could have altered the picture of NS presented in this article. Treatment should take into account nutritional and psychological factors, as well as associated infections. Some risk factors deserve further investigation; therefore, we suggest a multicentric study with an etiological focus using a more operational definition of NS.

Review of epilepsy care in the Democratic Republic of the Congo.

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.

The current status of neglected tropical diseases in Japan: A scoping review.

Little attention has been paid to neglected tropical diseases (NTDs) in high-income countries and no literature provides an overview of NTDs in Japan. This scoping review aims to synthesize the latest evidence and information to understand epidemiology of and public health response to NTDs in Japan. Using three academic databases, we retrieved articles that mentioned NTDs in Japan, written in English or Japanese, and published between 2010 and 2020. Websites of key public health institutions and medical societies were also explored. From these sources of information, we extracted data that were relevant to answering our research questions. Our findings revealed the transmission of alveolar echinococcosis, Buruli ulcer, Chagas disease, dengue, foodborne trematodiases, mycetoma, scabies, and soil-transmitted helminthiasis as well as occurrence of snakebites within Japan. Other NTDs, such as chikungunya, cystic echinococcosis, cysticercosis, leishmaniasis, leprosy, lymphatic filariasis, rabies, and schistosomiasis, have been imported into the country. Government agencies tend to organize surveillance and control programs only for the NTDs targeted by the Infectious Disease Control Law, namely, echinococcosis, rabies, dengue, and chikungunya. At least one laboratory offers diagnostic testing for each NTD except for dracunculiasis, human African trypanosomiasis, onchocerciasis, and yaws. No medicine is approved for treatment of Chagas disease and fascioliasis and only off-label use drugs are available for cysticercosis, opisthorchiasis, human African trypanosomiasis, onchocerciasis, schistosomiasis, and yaws. Based on these findings, we developed disease-specific recommendations. In addition, three policy issues are discussed, such as lack of legal frameworks to organize responses to some NTDs, overreliance on researchers to procure some NTD products, and unaffordability of unapproved NTD medicines. Japan should recognize the presence of NTDs within the country and need to address them as a national effort. The implications of our findings extend beyond Japan, emphasizing the need to study, recognize, and address NTDs even in high-income countries.

Cytotaxonomic characterization and estimation of migration patterns of onchocerciasis vectors (Simulium damnosum sensu lato) in northwestern Ethiopia based on RADSeq data.

BACKGROUND: While much progress has been made in the control and elimination of onchocerciasis across Africa, the extent to which vector migration might confound progress towards elimination or result in re-establishment of endemism in areas where transmission has been eliminated remains unclear. In Northern Ethiopia, Metema and Metekel-two foci located near the Sudan border-exhibit continuing transmission. While progress towards elimination has been faster in Metema, there remains a problematic hotspot of transmission. Whether migration from Metekel contributes to this is currently unknown. METHODOLOGY/PRINCIPLE FINDINGS: To assess the role of vector migration from Metekel into Metema, we present a population genomics study of 151 adult female vectors using 47,638 RADseq markers and mtDNA CoI sequencing. From additional cytotaxonomy data we identified a new cytoform in Metema, closely related to S. damnosum s.str, here called the Gondar form. RADseq data strongly indicate the existence of two distinctly differentiated clusters within S. damnosum s.l.: one genotypic cluster found only in Metema, and the second found predominantly in Metekel. Because blackflies from both clusters were found in sympatry (in all four collection sites in Metema), but hybrid genotypes were not detected, there may be reproductive barriers preventing interbreeding. The dominant genotype in Metema was not found in Metekel while the dominant genotype in Metekel was found in Metema, indicating that (at the time of sampling) migration is primarily unidirectional, with flies moving from Metekel to Metema. There was strong differentiation between clusters but little genetic differentiation within clusters, suggesting migration and gene flow of flies within the same genetic cluster are sufficient to prevent genetic divergence between sites. CONCLUSIONS/SIGNIFICANCE: Our results confirm that Metekel and Metema represent different transmission foci, but also indicate a northward movement of vectors between foci that may have epidemiological importance, although its significance requires further study.

Significant reduction of blackfly densities in persistent onchocerciasis area following pilot implementation of an environment friendly approach (Slash and Clear).

The effectiveness of the "Slash and Clear" method in reducing blackfly populations in low transmission areas is established, but its impact in high transmission settings with large rivers and dense vectors is yet to be proven. A community-based intervention study was conducted in the Mbam Valley, Centre Cameroon, involving two sites: Bayomen (control) and Biatsota (intervention). In each arm, baseline blackfly densities were collected over one year using the human landing method. The intervention consisted of destroying the trailing vegetation where blackflies breed. Blackfly densities were collected post-intervention to assess the impact of the intervention. Post-intervention data showed a 50.8% reduction in blackfly density in Biatsota (mean number of collected blackflies from 1936 to 953), while a reduction of 26.7% was observed in Bayomen (mean number of collected blackflies from 2418 to 1774). The reduction rate attributable to the intervention was 32.9%. Statistical analysis confirmed that the reduction in blackfly density was significantly greater in the intervention site. This study demonstrates the feasibility and significant impact of the "Slash and Clear" method in high transmission areas. However, further research is required to assess its long-term effects and determine how this strategy can be scaled up and sustained until onchocerciasis elimination is achieved.

Treatment and prevention of epilepsy in onchocerciasis-endemic areas is urgently needed.

BACKGROUND: There is increasing epidemiological evidence supporting the association between onchocerciasis and seizures, reinforcing the concept of onchocerciasis-associated epilepsy (OAE). The aim of this paper is to provide an update on the new knowledge about OAE and to propose recommendations to the World Health Organization how to address this public health problem. MAIN TEXT: During the 2nd International Workshop on OAE held on 19-21 September, 2023, in Antwerp, Belgium, participants recognised OAE as a substantial yet neglected public health problem, particularly in areas of sub-Saharan Africa where onchocerciasis remains hyperendemic. Evidence from prospective population-based studies suggest that strengthening onchocerciasis elimination efforts leads to a significant reduction of OAE incidence. There is a need to validate an OAE case definition to estimate the burden of disease and identify onchocerciasis-endemic areas requiring intensification of onchocerciasis elimination programmes and integration of epilepsy care. It is expected that raising awareness about OAE will boost the population uptake of ivermectin. The implementation of a community-based epilepsy treatment programme offering free anti-seizure medications (ASMs) has shown high effectiveness in reducing the frequency of seizures and improving the overall quality of life of people with epilepsy. CONCLUSIONS: To reduce OAE burden, enhanced collaboration between onchocerciasis and mental health programmes at community, national, and international levels is required. Urgent efforts are needed to ensure the uninterrupted provision of free ASMs in onchocerciasis-endemic areas. Furthermore, OAE should be included in the quantification of the onchocerciasis disease burden.

Successful completion of onchocerciasis elimination mapping (OEM) in Niger, West Africa.

BACKGROUND: By 1987, onchocerciasis in Niger had been successfully controlled in the six endemic river basins. In 2017, onchocerciasis elimination mapping (OEM) was carried out to determine if there was any ongoing transmission in the country as a whole. METHODS: The recommended OEM procedures were implemented. RESULTS: Ten districts, that included 35 villages, required field investigation as sites of possible transmission. None of these were found capable of supporting black fly breeding, nor was there any evidence of the presence of Simulium sp. flies. CONCLUSIONS: The implementation of OEM indicates that there is no transmission of onchocerciasis currently taking place in these newly assessed sites in Niger.