Gaps in treatment of epileptic seizures in a Zambian rural area.

BACKGROUND: Epilepsy is a multifactorial neurological disorder, including parasitic infections of the brain such as neurocysticercosis (NCC). People with epileptic seizures (PWES) in low and middle-income countries often do not receive appropriate treatment, which besides epileptic seizures, may also lead to reduced quality of life and possibly death. The objective of this study was to describe gaps in treatment of epileptic seizures in a Zambian rural area. METHODS: A cross-sectional study was conducted in Sinda district of Zambia between August and October 2018. PWES identified from clinic records and with the help of community healthcare workers were recruited. Two questionnaires, one to PWES and the other to local healthcare workers, were administered to describe the treatment gap. RESULTS: A total of 146 PWES and 43 healthcare workers were interviewed. Of the 146 PWES, 131 had taken anti-seizure medication (ASM) at some point since their seizure onset, of which 49.6% were on current treatment. Only 18.3% were on continuous ASM, an overall treatment gap of 83.6%. Over 55% of healthcare workers did not know the relationship between epilepsy and NCC. The risk factors associated with lack of appropriate treatment were stock-outs of ASMs, lack of diagnostic equipment, poor patient follow-up, and PWES opting for traditional medicine. CONCLUSION: The treatment gap is substantial in Sinda district. The causes are multifactorial, involving shortcomings at the level of healthcare facilities, communities, and individuals. Directed training of healthcare workers and significant improvements in the supply and dispensing of ASMs will be key in substantially reducing the gap.

Human health and economic impact of neurocysticercosis in Uganda.

OBJECTIVE: Neurocysticercosis (NCC), caused by the pork tapeworm Taenia solium, is a major cause of acquired epilepsy in endemic regions. The Republic of Uganda, one of the great-lakes nations in East Africa, has undergone major strives of political instability in the past century, impeding control of T. solium and other foodborne diseases. Building on data on the epidemiology of NCC, we aimed to assess the health and economic impact of NCC-associated epilepsy and headache in Uganda. METHODS: We used DisMod II to generate an internally consistent, complete and age-stratified set of epidemiological parameters for NCC epilepsy, and subsequently modelled the NCC headache incidence from the NCC epilepsy incidence. The health impact of both conditions was quantified in terms of Disability-Adjusted Life Years (DALYs), while the economic impact was quantified as the cost of illness associated with direct healthcare costs, patient costs and productivity losses. For both assessments, we adopted an incidence perspective and used 2010 as reference year. Uncertainty was propagated using 100,000 Monte Carlo simulations. RESULTS: In 2010, NCC was estimated to cause more than 9000 (CI: 7685-11,071) new cases of epilepsy and nearly 1500 new cases of headache, eventually leading to nearly 3000 deaths. Overall, it was estimated that NCC led to more than 170,000 DALYs (5.2 per 1000 person years; 16 per incident case) and an economic loss of more than USD 75 million (8000 per incident case). Non-fatal health outcomes were the largest contributors to the overall health impact, while productivity losses dominated the NCC cost of illness. CONCLUSIONS: NCC imposes a substantial burden on public health and the economy in Uganda with poor attention given to this public health problem. Increased awareness among governments, international agencies, and general public, as well as targeted intervention studies using a One Health approach are needed to reduce the significant burden of NCC in Uganda.

Assessing the burden of Taenia solium cysticercosis in Burundi, 2020.

BACKGROUND: Taenia solium cysticercosis is a zoonotic disease that is endemic in many low- and middle-income countries where risk factors for disease transmission are present. The economic impact of cysticercosis on public health and on the pig production sector is not well known in many of those countries, including Burundi. This study aimed at estimating the burden of T. solium cysticercosis in Burundi including data on humans and pigs. METHODS: Epidemiological and economic data were collected from literature up to July 30, 2021 and governmental and non-governmental agencies. Direct and indirect costs for neurocysticercosis (NCC)-associated epilepsy and losses due to porcine cysticercosis were estimated to assess the economic burden, while the health burden was estimated using zoonotic disability-adjusted life years (zDALYs). Different probability distributions (Uniform, Beta, Dirichlet and Gamma) were applied depending on the type of epidemiological parameter. Monte Carlo simulations and 100,000 iterations were used to calculate the 95% uncertainty interval (UI) for each parameter and perform sensitivity analyses. RESULTS: In Burundi, 4.26 million USD (95% UI, 1,858,308-8,190,951) were estimated as economic impact due to T. solium cysticercosis in humans and pigs, of which 40.2% (95% UI, 10.3-75.1) of the total costs were due to NCC-associated epilepsy and 59.8% (95% UI, 24.9-89.7) of the losses due to porcine cysticercosis. The cost per NCC-associated epilepsy case was 72 USD (95% UI, 25-168), representing 30.8% of the GDP per capita in 2020. The probable incident cases and deaths for NCC-associated epilepsy were 9065 (95% UI, 2370-16,716) and 61 (95% UI, 16-114), respectively. More than 2 zDALYs (95% UI, 1.1-3.4) per thousand person-years was estimated, of which an average of 1.3 DALYs [0;0] (95% UI, 0.3-2.6) was due to NCC- associated epilepsy and 0.8 animal loss equivalents (ALEs) (95% UI, 0.3-1.5) due to porcine cysticercosis. CONCLUSIONS: This study provides evidence of a significant burden of T. solium cysticercosis for Burundi's population. We urge policy makers to use these evidence-based results and put T. solium cysticercosis on the public health agenda of the country. This study recommends urgent action to find solutions for integrated control strategies for T. solium cysticercosis in Burundi.

Operational characteristics of an antibody detecting point of care test for Taenia solium infections in a community and hospital setting.

BACKGROUND: Diagnostic test evaluation includes measures of performance and assessment of operational characteristics. The latter focuses on end-user understanding of instructions to perform the test, ease of use, test turnaround time and ease of result interpretation. This study aimed to assess user comprehension of training for and ease of use of a Taenia solium point of care test (TS POC) evaluated in a community and hospital setting in Zambia and Tanzania, respectively. METHODS: The TS POC is a three-step in-house-produced rapid diagnostic test (RDT) for the simultaneous detection of taeniosis (TST) and cysticercosis (TSCC) antibodies. Data collected by administering questionnaires to 29 end-users and from the main evaluation database was analyzed quantitatively. RESULTS: End-users (28/29, 97%) perceived that the training they received for performing the test was sufficient. They performed 4080 tests, of which 80 were invalid. The community-based study and TST tests had higher invalid rates. The overall result interpretation was within the acceptable range of RDTs with an overall disagreement between readers of 3.3%. The Kappa coefficient of agreement was 85 and 82% for TSCC and TST, respectively. There was more disagreement among readers in the community-based study. CONCLUSION: End-users rated the TS POC kit moderate in terms of ease of use citing long test turnaround time and difficulties in using the blood transfer device. Overall, the operational performance of the TS POC kit and end-users was within the established acceptable performance range.

Modelling for Taenia solium control strategies beyond 2020.

The cestode Taenia solium is responsible for a considerable cross-sectoral health and economic burden due to human neurocysticercosis and porcine cysticercosis. The 2012 World Health Organization (WHO) roadmap for neglected tropical diseases called for the development of a validated strategy for control of T. solium; however, such a strategy is not yet available. In 2019, WHO launched a global consultation aimed at refining the post-2020 targets for control of T. solium for a new roadmap for neglected tropical diseases. In response, two groups working on taeniasis and cysticercosis mathematical models (cystiSim and EPICYST models), together with a range of other stakeholders organized a workshop to provide technical input to the WHO consultation and develop a research plan to support efforts to achieve the post-2020 targets. The workshop led to the formation of a collaboration, CystiTeam, which aims to tackle the population biology, transmission dynamics, epidemiology and control of T. solium through mathematical modelling approaches. In this paper, we outline developments in T. solium control and in particular the use of modelling to help achieve post-2020 targets for control of T. solium. We discuss the steps involved in improving confidence in the predictive capacities of existing mathematical and computational models on T. solium transmission, including model comparison, refinement, calibration and validation. Expanding the CystiTeam partnership to other research groups and stakeholders, particularly those operating in different geographical and endemic areas, will enhance the prospects of improving the applicability of T. solium transmission models to inform taeniasis and cysticercosis control strategies.

Taenia solium est un cestode qui entraîne une charge intersectorielle économique et sanitaire considérable en provoquant une neurocysticercose humaine et une cysticercose porcine. La feuille de route sur les maladies tropicales négligées, publiée en 2012 par l'Organisation mondiale de la Santé (OMS), appelait à développer une stratégie de contrôle validée pour T. solium ; cependant, cette stratégie n'est pas encore disponible à l'heure actuelle. En 2019, l'OMS a lancé une procédure de consultation mondiale visant à préciser les objectifs de contrôle de T. solium après 2020, afin de rédiger une nouvelle feuille de route sur les maladies tropicales négligées. Deux groupes qui travaillent sur des modèles mathématiques de taeniasis et cysticercose (modèles cystiSim et EPICYST) ainsi qu'une série d'autres intervenants ont donc organisé un atelier pour fournir une contribution technique à cette consultation et développer un programme de recherche destiné à soutenir les efforts de réalisation des objectifs ultérieurs à 2020. L'atelier a donné naissance à une collaboration, CystiTeam, qui s'intéresse à la biologie des populations, à la dynamique de transmission, à l'épidémiologie et au contrôle de T. solium en employant des méthodes de modélisation mathématique. Le présent document retrace l'évolution du contrôle de T. solium, en particulier l'usage de la modélisation pour contribuer à atteindre les objectifs d'après 2020 en la matière. Nous abordons les diverses étapes de renforcement de la confiance accordée aux capacités prédictives des modèles mathématiques et informatiques existants sur la transmission de T. solium, notamment la comparaison, l'optimisation, le calibrage et la validation des modèles. Élargir le partenariat CystiTeam en intégrant d'autres groupes de recherche et intervenants, surtout ceux opérant dans différentes zones géographiques et endémiques, accroîtra les chances d'amélioration de l'applicabilité pour les modèles de transmission de T. solium, et permettra ainsi d'établir des stratégies de lutte contre la taeniasis et la cysticercose.

El cestodo Taenia solium es responsable de una importante carga sanitaria y económica transversal debido a la neurocisticercosis humana y la cisticercosis porcina. En la hoja de ruta de la Organización Mundial de la Salud (OMS) de 2012 sobre las enfermedades tropicales desatendidas se solicitaba la elaboración de una estrategia validada para el control de T. solium; sin embargo, dicha estrategia aún no está disponible. En 2019, la OMS inició una consulta mundial destinada a perfeccionar los objetivos de control de T. solium aplicables a partir de 2020 con miras a elaborar una hoja de ruta nueva sobre las enfermedades tropicales desatendidas. Consecuentemente, dos grupos que trabajan en modelos matemáticos de teniasis y cisticercosis (modelos cystiSim y EPICYST), junto con un grupo de otros interesados, organizaron un seminario para contribuir técnicamente a la consulta de la OMS y elaborar un plan de investigación a fin de apoyar los esfuerzos para lograr los objetivos a partir de 2020. El seminario impulsó la formación de un equipo de colaboración, CystiTeam, para abordar la biología de la población, la dinámica de la transmisión, la epidemiología y el control de T. solium mediante enfoques de modelos matemáticos. En el presente documento se describen las novedades en el control de T. solium y, en particular, la aplicación de modelos para ayudar a lograr los objetivos a partir de 2020 sobre el control de T. solium. Se analizan las etapas necesarias para mejorar la confianza en las capacidades de predicción de los modelos matemáticos y computacionales existentes sobre la transmisión de T. solium, incluyendo la comparación, el perfeccionamiento, el ajuste y la validación de los modelos. La ampliación de la asociación CystiTeam a otros grupos de investigación e interesados, en particular los que operan en diferentes zonas geográficas y endémicas, reforzará las perspectivas de mejorar la aplicabilidad de los modelos sobre las transmisión de T. solium para fundamentar las estrategias de control de la teniasis y la cisticercosis.

Epidemiology and surveillance of human (neuro)cysticercosis in Europe: is enhanced surveillance required?

OBJECTIVES: To report on relevant national surveillance systems of (N)CC and taeniasis (the infection with the adult tapeworm) in the European Union/European Economic Area and to assess the magnitude of (N)CC occurrence by retrieving information on cases for the period 2000-2016. METHODS: (N)CC cases were retrieved via national reporting systems, a systematic literature search, contact with clinicians and a search for relevant 'International Statistical Classification of Diseases and Related Health Problems' (ICD)-based data. RESULTS: Mandatory notification systems for (N)CC were found in Hungary, Iceland and Poland. Ten cases were reported in Poland and none in Hungary and Iceland. Through the systematic literature review and information given by clinicians, 263 individual and 721 aggregated (N)CC cases from 19 European countries were identified. ICD-based data were obtained from five countries. From 2000 to 2016, a total of 3489 cases (N)CC cases were coded: 832 in Italy, eight in Latvia, 357 in Portugal, 2116 in Spain and 176 in Sweden. CONCLUSION: Despite being classified as a possible eradicable disease, (N)CC is still diagnosed across Europe, yet its true extent and impact remain unclear.

OBJECTIFS: Rapporter sur les systèmes nationaux de surveillance pertinents de la (neuro)cysticercose (N)CC et de la téniase (infection par le ténia adulte) dans l'Union européenne/l'Espace économique européen, et évaluer l'ampleur de l'occurrence de la (N)CC en reprenant des informations sur les cas durant la période 2000-2016. MÉTHODES: Les cas de (N)CC ont été repris à partir des systèmes nationaux de notification, une recherche systématique de la littérature, des contacts avec des cliniciens et une recherche de données pertinentes basées sur la 'Classification Statistique Internationale des Maladies et Problèmes de Santé Connexes' (ICD). RÉSULTATS: Des systèmes de notification obligatoires pour la (N)CC ont été trouvés en Hongrie, en Islande et en Pologne. Dix cas ont été rapportés en Pologne et aucun en Hongrie et en Islande. Grâce à la revue systématique de la littérature et aux informations fournies par les cliniciens, 263 cas individuels et 721 cas agrégés de (N)CC de 19 pays européens ont été identifiés. Des données ICD ont été obtenues de cinq pays. De 2000 à 2016, un total de 3489 cas de (N)CC ont été codés: 832 en Italie, 8 en Lettonie, 357 au Portugal, 2116 en Espagne et 176 en Suède. CONCLUSION: Bien qu'elle soit classée comme une maladie pouvant être éradiquée, la (N)CC est toujours diagnostiquée à travers l'Europe, mais sa véritable ampleur et son impact restent incertains .

Endemicity of Taenia solium cysticercosis in pigs from Mbeya Rural and Mbozi districts, Tanzania.

BACKGROUND: Taenia solium taeniasis/cysticercosis is a disease of substantial economic and public health importance particularly in low-income countries. The disease was reported to be endemic in Mbeya Rural and Mbozi districts, in the southern highlands of Tanzania, the major pig production area in the country. In 2008, using B158/B60 antigen detection enzyme-linked immunosorbent assay (Ag-ELISA), porcine cysticercosis prevalence of up to 32% was reported in the districts. A number of interventions have been implemented in selected villages including an integrated approach consisting of improving pig confinement and selective treatment of pigs with oxfendazole. Mass drug administration with praziquantel targeting schistosomiasis, with an expected effect on T. solium, was also provided to school-age children in the area. This study aimed at providing an update on prevalence and intensities of porcine cysticercosis; and assessing farmers' knowledge, attitudes and practices which could be associated to disease transmission in the area. The study involved a questionnaire survey conducted using face-to-face household interviews with 890 consenting farmers; and carcass dissections performed on 282 pigs randomly selected from the surveyed households. RESULTS: Twenty-six pigs (9.2%) were infected with T. solium; of which two-thirds (65.4%) had light to moderate infection intensities (1-1000 cysticerci), and one-third (34.6%) had heavy intensities (> 1000 cysticerci). Questionnaire results showed that only 5.7% of the respondents perceived T. solium cysticercosis to be an important disease in pigs. About 18.5% of the respondents were aware of T. solium taeniasis, but 32% of them were unaware of how the infection is acquired. Half of the respondents had seen cysticerci in pork, of whom 61% were not aware that consumption of infected pork could cause taeniasis. Latrines were observed to often (90%) lack doors with 45% considered accessible to pigs. CONCLUSIONS: This study provided an evidence that the disease was still endemic in the area. Poor knowledge of farmers, attitudes, and risky practices responsible for disease perpetuation were also revealed. A One Health approach targeting the whole area incorporating improvement of farmer knowledge regarding disease transmission needs to be trialed as a feasible approach to control.

Collaboration Spanning Two Continents: An Online Master's Degree in Tropical Animal Health.

A joint international program in Tropical Animal Health was launched in 2016 by the Institute of Tropical Medicine, Antwerp, Belgium, and the Department of Veterinary Tropical Diseases, Faculty of Veterinary Science, University of Pretoria. This program is flexible in time, place, and curriculum, allowing part-time students to apply the program's learning outcomes directly in their daily work environment. This article focuses on the major challenges and issues related to developing an international joint program in general and how these challenges were addressed. Challenges such as incompatibility of admission procedures, merging academic calendars, and quality assurance mechanisms were mitigated partly by the type of collaboration and partly by using a joint e-learning platform. The e-learning format proved to be a solution for particular challenges such as mobility issues, joint development of course material, and administrative processes. Furthermore, we present the results of a survey on the experiences of graduates and facilitators in this unique joint, web-based program.

Stepwise approach for the control and eventual elimination of Taenia solium as a public health problem.

BACKGROUND: Taenia solium taeniosis/cysticercosis is a public health and agricultural problem, especially in low-income countries, and has been ranked the top foodborne parasitic hazard globally. In 2012, the World Health Organization published a roadmap that called for a validated strategy for T. solium control and elimination by 2015. This goal has not been met, and validated evidence of effective control or elimination in endemic countries is still incomplete. Measuring and evaluating success of control programmes remains difficult, as locally acceptable targets have not been defined as part of the 2012 roadmap nor from other sources, and the performance of tools to measure effect are limited. DISCUSSION: We believe that an international agreement supported by the tripartite World Health Organization, Food and Agriculture Organization of the United Nations, and World Organisation for Animal Health is needed to facilitate endemic countries in publicising SMART (Specific, Measurable, Achievable/attainable, Relevant, Time-bound) country-level control target goals. These goals should be achievable through locally acceptable adoption of options from within a standardised 'intervention tool-kit', and progress towards these goals should be monitored using standardised and consistent diagnostics. Several intervention tools are available which can contribute to control of T. solium, but the combination of these - the most effective control algorithm - still needs to be identified. In order to mount control efforts and ensure political commitment, stakeholder engagement and funding, we argue that a stepwise approach, as developed for Rabies control, is necessary if control efforts are to be successful and sustainable. CONCLUSIONS: The stepwise approach can provide the framework for the development of realistic control goals of endemic areas, the implementation of intervention algorithms, and the standardised monitoring of the evaluation of the progress towards obtaining the control target goals and eventually elimination.

Assessment of the societal cost of Taenia solium in Angónia district, Mozambique.

BACKGROUND: The zoonotic parasite Taenia solium is endemic in Angónia district, Tete province, Mozambique, though the burden of the disease complex is unknown. METHODS: As part of two cross-sectional studies on human and porcine cysticercosis in the area, unique epidemiological and cost data were collected in Angónia district, Mozambique in 2007. These data provided the basis for the assessment of the societal cost of T. solium in the district, which estimates the impact of the disease on human and pig populations and includes both health and economic approaches in the analysis. RESULTS: Approximately 0.7% (95% Uncertainty Interval (UI), 0.4-0.9) and 0.4% (95% UI, 0.2-0.6) of the total population in the district was estimated to suffer from neurocysticercosis (NCC)-associated epilepsy and headache. The estimated average number of disability-adjusted life years (DALYs) due to NCC-associated epilepsy and headache was 6 (95% UI, 4-8) per thousand persons per year. The total annual costs due to T. solium cysticercosis were estimated at 90,000 USD (95% UI, 39,483-201,463) of which 72% (95% UI, 45-91) were costs linked to human cysticercosis and 28% (95% UI, 9.5-55) to pig production losses. The annual economic burden per NCC-associated epilepsy case in the district amounted to 33 USD (95% UI, 10-76). CONCLUSIONS: In this highly endemic area of Mozambique a large number of individuals suffer from symptoms associated with NCC. Healthy years of life are lost and people are left living with disabilities. Infected pork poses a serious risk to the community and affects the economy of smallholder farmers. Cost for treatment and hospitalization of patients with NCC-associated epilepsy, and lack of productivity and inability of suffering patients to work, further hinder socioeconomic development. Feasible solutions framed within a country specific algorithm and stepwise approaches are needed to control the parasite in the country.

Are we ready for Taenia solium cysticercosis elimination in sub-Saharan Africa?

The World Health Organization announced in November 2014 at the fourth international meeting on 'the control of neglected zoonotic diseases - from advocacy to action', that intervention tools for eliminating Taenia solium taeniosis/cysticercosis (TSTC) are in place. The aim of this work was to elucidate theoretical outcomes of various control options suggested for TSTC elimination in sub-Saharan Africa (SSA) over a 4-year period. Our current knowledge regarding T. solium epidemiology and control primarily builds on studies from Latin America. A simple transmission model - built on data from Latin America - has been used to predict the effect of various interventions such as mass treatment of humans, vaccination and treatment of pigs, and health education of communities, potentially leading to change in bad practices and reducing transmission risks. Based on simulations of the transmission model, even a 4-year integrated One Health approach fails to eliminate TSTC from a small community and in all simulations, the prevalence of human taeniosis and porcine cysticercosis start to rise as soon as the programmes end. Our current knowledge regarding transmission and burden of TSTC in SSA is scarce and while claiming to be tool ready, the selection of diagnostic and surveillance tools, as well as the algorithms and stepwise approaches for control and elimination of TSTC remain major challenges.

Hair cortisol and dehydroepiandrosterone concentrations in naturally Taenia solium infected pigs in Tanzania.

The aim of this study was to measure hair cortisol and dehydroepiandrosterone (DHEA) concentrations in naturally Taenia solium infected and non-infected control pigs and assess the effect of an environmental change on the aforementioned parameters. Three hair patches were obtained from 13 T. solium infected and 15 non-infected controls sows, respectively corresponding to 3 time points (prior to, at and approximately two weeks after arrival at the research facility). Cortisol and DHEA were extracted using methanol and analysed by radio immune assay. Mean hair cortisol concentrations were significantly lower (p<0.001) in T. solium infected (4.7±3.0pg/mg) compared to control pigs (9.0±3.7pg/mg) prior to arrival at the research facility, however no significant difference was observed between the two groups at arrival and after approximately two weeks. Similar patterns were also observed for DHEA concentrations (infected pigs 253.9±82.3pg/mg, control pigs 387.7±116.4pg/mg) (p<0.001). Results showed that lean animals had significantly higher cortisol concentrations in both groups, infected and controls pigs, while DHEA was not significantly different between lean and normal animals. Results of this study have shown that an environmental change could have an effect on pigs' hormonal levels suggesting an undergoing adaptation process. After the pigs were kept under the same conditions, fed and watered ad libitum, no significant differences were observed between the groups, but a drop in DHEA concentrations was observed in all the pigs. Weight however had an effect on cortisol levels as lean animals had significantly higher cortisol concentrations in both groups, compared to normal pigs.

The Vicious Worm education tool improves the knowledge of community health workers on Taenia solium cysticercosis in Rwanda.

The pork tapeworm Taenia solium causes human taeniasis and cysticercosis when ingested as viable cysts and eggs, respectively. Despite its high health burden in low-income countries, knowledge of the parasite in endemic areas such as Rwanda is often limited. Here, we assess whether The Vicious Worm education software can increase knowledge in endemic areas of Rwanda. A cross-sectional mixed-methods study was conducted to evaluate knowledge about T. solium among community health workers trained using the Vicious Worm education software. Knowledge was assessed before, immediately after, and four weeks after the training. The health workers perceptions of the software were analysed thematically. A total of 207 community health workers were recruited from Nyamagabe district in Southern Province, Rwanda. Participants were composed of males (33.5%) and females (66.5%), aged between 22 and 68 years, and most (71%) had only completed primary education. Knowledge of cysticercosis at baseline was low, particularly knowledge of human cysticercosis and neurocysticercosis. The overall knowledge score increased significantly after training and was maintained four weeks after the training. Overall, insufficient knowledge was associated with neurocysticercosis-related questions, which after the training, remained relatively lower compared to questions of other categories. Participants reported the software to be user-friendly and educational. Digital illiteracy and the lack of smartphones were among the critical challenges highlighted in responses. This study has shown gaps in knowledge regarding T. solium infections within rural Rwanda, particularly neurocysticercosis. Health education using the Vicious Worm education software should be considered in integrated control programs.

Could a ring treatment approach be proposed to control Taenia solium transmission in a post elimination setting? A pilot study in Zambia.

BACKGROUND: Geographically targeted Taenia solium ring approaches consisting of treating individuals within a radius of 100-meter of a cysticercosis positive pig have been trialled in Peru. This study explored if a similar approach could be proposed to control T. solium transmission in a post elimination setting in Zambia, focussing on community members' willingness to be sampled and treated. METHODOLOGY AND PRINCIPAL FINDINGS: The study was conducted in a community where elimination of active T. solium transmission was achieved. All eligible pigs and people were sampled, at 4- to 6-monthly intervals, followed by implementation of the ring treatment approach. This implied that whenever a pig was seropositive for cysticercosis during sampling, every human and pig residing in a radius of 50-meters of the seropositive pig would be treated. The results of the positive human stool samples were used to create the rings, whenever no pigs were positive. From June 2018 to October 2019, four samplings, followed by ring treatments were conducted. Between 84% and 91% of the willing people provided a stool sample, covering 46% to 59% of the total population living in the study area. Between 78% and 100% of the eligible pigs got sampled. Three ring treatments were based on porcine seropositivity and one on taeniosis results. Two to four rings were opened per sampling. During the ring treatments, between 89% and 100% of the eligible human and pig population living within a ring was treated. CONCLUSIONS: Participants were willing to participate and get treatment, once the rings were opened. However, the utility of ring treatment approaches in a post elimination setting needs further evaluation, given the lack of highly accurate diagnostic tools for porcine cysticercosis and the challenges in obtaining stool samples. The ring treatment approach adopted should be further improved before recommendations to public health authorities can be given.

Evaluation of a point-of-care test for the diagnosis of Taenia solium neurocysticercosis in rural southern Tanzania: a diagnostic accuracy study.

BACKGROUND: Neurocysticercosis is a common cause of epilepsy in Taenia solium-endemic areas in sub-Saharan Africa but is often undiagnosed because of an absence of affordable diagnostic tools. This study evaluated the diagnostic accuracy of a T solium cysticercosis antibody-detecting lateral-flow point-of-care assay (TS POC test) for the neuroimaging-based diagnosis of neurocysticercosis. METHODS: Patients with epileptic seizures or severe progressive headache were recruited consecutively from three hospitals in southern Tanzania. All patients were tested with the TS POC test. All patients positive for cysticercosis on the TS POC test and every tenth patient who was negative for cysticercosis received a brain CT examination and underwent reference testing for T solium cysticercosis (ie, rT24H-EITB, LLGP-EITB, and antigen ELISA). The primary outcome of the study was the sensitivity of the TS POC test for the diagnosis of neurocysticercosis. FINDINGS: Of the 601 recruited participants, 102 (17%) tested positive for cysticercosis with the TS POC test. Overall, 48 (62%) of the 77 patients positive for cysticercosis and five (17%) of the 29 patients negative for cysticercosis on the TS POC test had CT-confirmed neurocysticercosis. The TS POC test yielded a sensitivity of 49% (uncertainty interval [UI] 41-58) for neurocysticercosis. Sensitivity was similar to that of the rT24H-EITB (44%, UI 37-51) and the antigen ELISA (50%, 43-56). For the subset of neurocysticercosis cases with at least one active (ie, vesicular) lesion, sensitivity was above 98% for the TS POC test, the rT24H-ETIB, and the antigen ELISA. INTERPRETATION: The TS POC test showed promising results for the diagnosis of neurocysticercosis in patients with vesicular lesions, which need to be confirmed in a larger study. This test could be considered to support policies on screening patients with suspected neurocysticercosis in clinical settings, which would allow appropriate referral for neuroimaging and early treatment. FUNDING: German Federal Ministry of Education and Research and the European & Developing Countries Clinical Trials Partnership. TRANSLATION: For the Swahili translation of the abstract see Supplementary Materials section.

Quantitative 3D histochemistry reveals region-specific amyloid-ß reduction by the antidiabetic drug netoglitazone.

A hallmark of Alzheimer's disease (AD) is the extracellular aggregation of toxic amyloid-beta (Aß) peptides in form of plaques. Here, we identify netoglitazone, an antidiabetic compound previously tested in humans, as an Aß aggregation antagonist. Netoglitazone improved cognition and reduced microglia activity in a mouse model of AD. Using quantitative whole-brain three-dimensional histology (Q3D), we precisely identified brain regions where netoglitazone reduced the number and size of Aß plaques. We demonstrate the utility of Q3D in preclinical drug evaluation for AD by providing a high-resolution brain-wide view of drug efficacy. Applying Q3D has the potential to improve pre-clinical drug evaluation by providing information that can help identify mechanisms leading to brain region-specific drug efficacy.

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.

Direct and indirect regulation of ß-glucocerebrosidase by the transcription factors USF2 and ONECUT2.

Mutations in GBA1 encoding the lysosomal enzyme ß-glucocerebrosidase (GCase) are among the most prevalent genetic susceptibility factors for Parkinson's disease (PD), with 10-30% of carriers developing the disease. To identify genetic modifiers contributing to the incomplete penetrance, we examined the effect of 1634 human transcription factors (TFs) on GCase activity in lysates of an engineered human glioblastoma line homozygous for the pathogenic GBA1 L444P variant. Using an arrayed CRISPR activation library, we uncovered 11 TFs as regulators of GCase activity. Among these, activation of MITF and TFEC increased lysosomal GCase activity in live cells, while activation of ONECUT2 and USF2 decreased it. While MITF, TFEC, and USF2 affected GBA1 transcription, ONECUT2 might control GCase trafficking. The effects of MITF, TFEC, and USF2 on lysosomal GCase activity were reproducible in iPSC-derived neurons from PD patients. Our study provides a systematic approach to identifying modulators of GCase activity and deepens our understanding of the mechanisms regulating GCase.

Neurocysticercosis Prevalence and Characteristics in Communities of Sinda District in Zambia: A Cross-Sectional Study.

BACKGROUND: This study aimed at describing the epidemiology of (neuro)cysticercosis as well as its clinical and radiological characteristics in a Taenia solium endemic district of Zambia. METHODS: This was part of a cross-sectional community-based study conducted in Sinda district to evaluate an antibody-detecting T. solium point-of-care (TS POC) test for taeniosis and (neuro)cysticercosis. All TS POC cysticercosis positive (CC+) participants and a subset of the TS POC cysticercosis negative (CC-) received a clinical evaluation and cerebral computed tomography (CT) examination for neurocysticercosis (NCC) diagnosis and staging. RESULTS: Of the 1249 participants with a valid TS POC test result, 177 (14%) were TS POC CC+ . Cysticercosis sero-prevalence was estimated to be 20.1% (95% confidence intervals [CI] 14.6-27.0%). In total, 233 participants received a CT examination (151 TS POC CC+ , 82 TS POC CC-). Typical NCC lesions were present in 35/151 (23%) TS POC CC+ , and in 10/82 (12%) TS POC CC- participants. NCC prevalence was 13.5% (95% CI 8.4-21.1%) in the study population and 38.0% (95% CI 5.2-87.4%) among people reporting epileptic seizures. Participants with NCC were more likely to experience epileptic seizures (OR = 3.98, 95% CI 1.34-11.78, p = 0.01) than those without NCC, although only 7/45 (16%) people with NCC ever experienced epileptic seizures. The number of lesions did not differ by TS POC CC status (median: 3 [IQR 1-6] versus 2.5 [IQR 1-5.3], p = 0.64). Eight (23%) of the 35 TS POC CC+ participants with NCC had active stage lesions; in contrast none of the TS POC CC- participants was diagnosed with active NCC. CONCLUSION: NCC is common in communities in the Eastern province of Zambia, but a large proportion of people remain asymptomatic.