CD4+ T cell calibration of antigen-presenting cells optimizes antiviral CD8+ T cell immunity.

Antiviral CD8+ T cell immunity depends on the integration of various contextual cues, but how antigen-presenting cells (APCs) consolidate these signals for decoding by T cells remains unclear. Here, we describe gradual interferon-α/interferon-ß (IFNα/ß)-induced transcriptional adaptations that endow APCs with the capacity to rapidly activate the transcriptional regulators p65, IRF1 and FOS after CD4+ T cell-mediated CD40 stimulation. While these responses operate through broadly used signaling components, they induce a unique set of co-stimulatory molecules and soluble mediators that cannot be elicited by IFNα/ß or CD40 alone. These responses are critical for the acquisition of antiviral CD8+ T cell effector function, and their activity in APCs from individuals infected with severe acute respiratory syndrome coronavirus 2 correlates with milder disease. These observations uncover a sequential integration process whereby APCs rely on CD4+ T cells to select the innate circuits that guide antiviral CD8+ T cell responses.

Early precursor T cells establish and propagate T cell exhaustion in chronic infection.

CD8+ T cells responding to chronic infections or tumors acquire an 'exhausted' state associated with elevated expression of inhibitory receptors, including PD-1, and impaired cytokine production. Exhausted T cells are continuously replenished by T cells with precursor characteristics that self-renew and depend on the transcription factor TCF1; however, their developmental requirements are poorly understood. In the present study, we demonstrate that high antigen load promoted the differentiation of precursor T cells, which acquired hallmarks of exhaustion within days of infection, whereas early effector cells retained polyfunctional features. Early precursor T cells showed epigenetic imprinting characteristic of T cell receptor-dependent transcription factor binding and were restricted to the generation of cells displaying exhaustion characteristics. Transcription factors BACH2 and BATF were key regulators with opposing functions in the generation of early precursor T cells. Overall, we demonstrate that exhaustion manifests first in TCF1+ precursor T cells and is propagated subsequently to the pool of antigen-specific T cells.

Transforming growth factor-ß-regulated mTOR activity preserves cellular metabolism to maintain long-term T cell responses in chronic infection.

Antigen-specific CD8+ T cells in chronic viral infections and tumors functionally deteriorate, a process known as exhaustion. Exhausted T cells are sustained by precursors of exhausted (Tpex) cells that self-renew while continuously generating exhausted effector (Tex) cells. However, it remains unknown how Tpex cells maintain their functionality. Here, we demonstrate that Tpex cells sustained mitochondrial fitness, including high spare respiratory capacity, while Tex cells deteriorated metabolically over time. Tpex cells showed early suppression of mTOR kinase signaling but retained the ability to activate this pathway in response to antigen receptor signals. Early transient mTOR inhibition improved long-term T cell responses and checkpoint inhibition. Transforming growth factor-ß repressed mTOR signaling in exhausted T cells and was a critical determinant of Tpex cell metabolism and function. Overall, we demonstrate that the preservation of cellular metabolism allows Tpex cells to retain long-term functionality to sustain T cell responses during chronic infection.

MYB orchestrates T cell exhaustion and response to checkpoint inhibition.

CD8+ T cells that respond to chronic viral infections or cancer are characterized by the expression of inhibitory receptors such as programmed cell death protein 1 (PD-1) and by the impaired production of cytokines. This state of restrained functionality-which is referred to as T cell exhaustion1,2-is maintained by precursors of exhausted T (TPEX) cells that express the transcription factor T cell factor 1 (TCF1), self-renew and give rise to TCF1- exhausted effector T cells3-6. Here we show that the long-term proliferative potential, multipotency and repopulation capacity of exhausted T cells during chronic infection are selectively preserved in a small population of transcriptionally distinct CD62L+ TPEX cells. The transcription factor MYB is not only essential for the development of CD62L+ TPEX cells and maintenance of the antiviral CD8+ T cell response, but also induces functional exhaustion and thereby prevents lethal immunopathology. Furthermore, the proliferative burst in response to PD-1 checkpoint inhibition originates exclusively from CD62L+ TPEX cells and depends on MYB. Our findings identify CD62L+ TPEX cells as a stem-like population that is central to the maintenance of long-term antiviral immunity and responsiveness to immunotherapy. Moreover, they show that MYB is a transcriptional orchestrator of two fundamental aspects of exhausted T cell responses: the downregulation of effector function and the long-term preservation of self-renewal capacity.

Transcription Factor IRF4 Promotes CD8+ T Cell Exhaustion and Limits the Development of Memory-like T Cells during Chronic Infection.

During chronic stimulation, CD8+ T cells acquire an exhausted phenotype characterized by expression of inhibitory receptors, down-modulation of effector function, and metabolic impairments. T cell exhaustion protects from excessive immunopathology but limits clearance of virus-infected or tumor cells. We transcriptionally profiled antigen-specific T cells from mice infected with lymphocytic choriomeningitis virus strains that cause acute or chronic disease. T cell exhaustion during chronic infection was driven by high amounts of T cell receptor (TCR)-induced transcription factors IRF4, BATF, and NFATc1. These regulators promoted expression of inhibitory receptors, including PD-1, and mediated impaired cellular metabolism. Furthermore, they repressed the expression of TCF1, a transcription factor required for memory T cell differentiation. Reducing IRF4 expression restored the functional and metabolic properties of antigen-specific T cells and promoted memory-like T cell development. These findings indicate that IRF4 functions as a central node in a TCR-responsive transcriptional circuit that establishes and sustains T cell exhaustion during chronic infection.

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.

Intact TP-53 function is essential for sustaining durable responses to BH3-mimetic drugs in leukemias.

Selective targeting of BCL-2 with the BH3-mimetic venetoclax has been a transformative treatment for patients with various leukemias. TP-53 controls apoptosis upstream of where BCL-2 and its prosurvival relatives, such as MCL-1, act. Therefore, targeting these prosurvival proteins could trigger apoptosis across diverse blood cancers, irrespective of TP53 mutation status. Indeed, targeting BCL-2 has produced clinically relevant responses in blood cancers with aberrant TP-53. However, in our study, TP53-mutated or -deficient myeloid and lymphoid leukemias outcompeted isogenic controls with intact TP-53, unless sufficient concentrations of BH3-mimetics targeting BCL-2 or MCL-1 were applied. Strikingly, tumor cells with TP-53 dysfunction escaped and thrived over time if inhibition of BCL-2 or MCL-1 was sublethal, in part because of an increased threshold for BAX/BAK activation in these cells. Our study revealed the key role of TP-53 in shaping long-term responses to BH3-mimetic drugs and reconciled the disparate pattern of initial clinical response to venetoclax, followed by subsequent treatment failure among patients with TP53-mutant chronic lymphocytic leukemia or acute myeloid leukemia. In contrast to BH3-mimetics targeting just BCL-2 or MCL-1 at doses that are individually sublethal, a combined BH3-mimetic approach targeting both prosurvival proteins enhanced lethality and durably suppressed the leukemia burden, regardless of TP53 mutation status. Our findings highlight the importance of using sufficiently lethal treatment strategies to maximize outcomes of patients with TP53-mutant disease. In addition, our findings caution against use of sublethal BH3-mimetic drug regimens that may enhance the risk of disease progression driven by emergent TP53-mutant clones.

CystiHuman: A model of human neurocysticercosis.

INTRODUCTION: The Taenia solium tapeworm is responsible for cysticercosis, a neglected tropical disease presenting as larvae in the body of a host following taenia egg ingestion. Neurocysticercosis (NCC), the name of the disease when it affects the human central nervous system, is a major cause of epilepsy in developing countries, and can also cause intracranial hypertension, hydrocephalus and death. Simulation models can help identify the most cost-effective interventions before their implementation. Modelling NCC should enable the comparison of a broad range of interventions, from treatment of human taeniasis (presence of an adult taenia worm in the human intestine) to NCC mitigation. It also allows a focus on the actual impact of the disease, rather than using proxies as is the case for other models. METHODS: This agent-based model is the first model that simulates human NCC and associated pathologies. It uses the output of another model, CystiAgent, which simulates the evolution of pig cysticercosis and human taeniasis, adding human and cyst agents, including a model of cyst location and stage, human symptoms, and treatment. CystiHuman also accounts for delays in the appearance of NCC-related symptoms. It comprises three modules detailing cyst development, seizure probability and timing, and intracranial hypertension/hydrocephalus, respectively. It has been implemented in Java MASON and calibrated in three endemic villages in Peru, then applied to another village (Rica Playa) to compare simulation results with field data in that village. RESULTS AND DISCUSSION: Despite limitations in available field data, parameter values found through calibration are plausible and simulated outcomes in Rica Playa are close to actual values for NCC prevalence and the way it increases with age and cases with single lesions. Initial simulations further suggest that short-term interventions followed by a rapid increase in taeniasis prevalence back to original levels may have limited impacts on NCC prevalence.

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.

Characterization of epithelial cells, connective tissue cells and immune cells in human upper airway mucosa by immunofluorescence multichannel image cytometry: a pilot study.

Epithelial, connective tissue and immune cells contribute in various ways to the pathophysiology of chronic rhinosinusitis (CRS). However, data of their distribution in upper airway mucosa are sparse. We aimed to provide quantitative, purely informative data on the distribution of these cell lineages and their coexpression patterns, which might help identifying, e.g., cells in the epithelium undergoing through epithelial-mesenchymal transition (EMT). For this purpose, we used immunofluorescence multichannel image cytometry (IMIC). We examined fixed paraffin-embedded tissue samples (FFPE) of six patients with chronic rhinosinusitis (CRS) and of three patients without CRS (controls). The direct-conjugated antibodies pancytokeratin, vimentin and CD45/CD18 were used for coexpression analysis in epithelial layer and lamina propria. Image acquisition and analysis were performed with TissueFAXS and StrataQuest, respectively. To distinguish positive from negative expression, a ratio between cell-specific immunostaining intensity and background was developed. Isotype controls were used as negative controls. Per patient, a 4.5-mm2 tissue area was scanned and a median of 14,875 cells was recognized. The most common cell types were cytokeratin-single-positive (26%), vimentin-single-positive (13%) and CD45/CD18-single-positive with CD45/CD18-vimentin-double-positive cells (29%). In the patients with CRS, CD45/CD18-single-positive cells were 3-6 times higher compared to the control patients. In the epithelial layer, cytokeratin-vimentin-double-positive EMT cells were observed 3-5 times higher in the patients with CRS than in the control patients. This study provided quantitative data for the distribution of crucial cell types in CRS. Future studies may focus on the distribution and coexpression patterns of different immune cells in CRS or even cancer tissue.

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.

High frequency of Taenia solium antigen positivity in patients admitted for neurological disorders in the Rural Hospital of Mosango, Democratic Republic of Congo.

BACKGROUND: The epidemiology of human cysticercosis and neurocysticercosis, caused by the larval stage of the pork tapeworm Taenia solium, is not well known in the Democratic Republic of Congo (DRC). Within a multicenter etiological and diagnostic study conducted by the NIDIAG consortium ("Better Diagnosis for Neglected Infections") and investigating several challenging syndromes, we consecutively evaluated from 2012 to 2015 all patients older than 5 years presenting with neurological disorders (neurology cohort) and with fever > 7 days (persistent fever cohort) at the rural hospital of Mosango, province of Kwilu, DRC. In both cohorts, etiological diagnosis relied on a systematic set of reference laboratory assays and on pre-established clinical case definitions. No neuroimaging was available in the study hospital. In this study, we determined the frequency of T. solium infection in both cohorts and explored in the neurology cohort its association with specific neurological presentations and final etiological diagnoses. METHODS: We conducted a post-hoc descriptive and analytic study on cysticercosis in the neurology and persistent fever cohorts, based on the presence in serum samples of circulating T. solium antigen using the B158/B60 enzyme-linked immunosorbent assay (ELISA) and of cysticercosis IgG using the LDBIO Cysticercosis Western Blot IgG assay. RESULTS: For the neurology cohort, 340 samples (of 351 enrolled patients) were available for analysis (males: 46.8%; mean age: 38.9 years). T. solium antigen positivity was found in 43 participants (12.6%; 95% confidence interval [CI] 9.3-16.7%), including 9 of 60 (15%) patients with epilepsy. Among the 148 samples available from the persistent fever cohort (males: 39.9%; mean age: 19.9 years), 7 were positive in the T. solium antigen ELISA (4.7%; 95% CI 1.9-9.5%; P = 0.009 when compared to the neurology cohort). No significant association was found within the neurology cohort between positivity and clinical presentation or final diagnoses. Of note, the IgG antibody-detecting assay was found positive in only four (1.3%) of the participants of the neurology cohort and in none of the persistent fever cohort. CONCLUSIONS: T. solium antigen positivity was found in at least 10% of patients admitted with neurological disorders in the Kwilu province, DRC, with no specific pattern of presentation. Further neuroimaging studies should be used to confirm whether neurocysticercosis is prevalent in this region.

Occurrence, Molecular Characteristics, and Antimicrobial Resistance of Escherichia coli O157 in Cattle, Beef, and Humans in Bishoftu Town, Central Ethiopia.

Escherichia coli O157 is a Shiga toxin-producing E. coli causing disease in humans. Cattle are the primary reservoir of the pathogen. Information regarding the contribution of cattle to diarrheal illnesses in humans through consumption of contaminated beef is scarce in Ethiopia. We collected samples from 240 cattle, 127 beef, and 216 diarrheic patients in Bishoftu town in Ethiopia to assess the occurrence and determine the virulence genes, genetic relatedness, and antimicrobial resistance of E. coli O157. E. coli O157 was detected in 7.1% of the rectal content samples from cattle in slaughterhouses, in 6.3% (n = 127) of the beef samples, and in 2.8% of the diarrheic patients' stool samples. All isolates were positive for eae gene, 24 (77%) of them were positive for stx2 gene (21 stx2c and 3 stx2a), whereas stx1 gene was not detected. Molecular typing grouped the isolates into eight pulsed-field gel electrophoresis pulsotypes with three pulsotypes containing isolates from all three sources, one pulsotype containing one isolate from human origin and one isolate from beef. The remaining four pulsotypes contained isolates unique either to beef or to humans. With the exception of 1 multidrug-resistant isolate from beef, which was resistant to 8 antimicrobial drugs, the remaining 30 isolates were susceptible to the 14 antimicrobials tested. In conclusion, the finding of genetically similar isolates in cattle, beef, and humans may indicate a potential transmission of E. coli O157 from cattle to humans through beef. However, more robust studies are required to confirm this epidemiological link.

Prevalence, Antimicrobial Resistance, and Molecular Characterization of Salmonella in Cattle, Beef, and Diarrheic Patients in Bishoftu, Ethiopia.

Within Ethiopia, there is a lack of information on the genetic relatedness of Salmonella from cattle, beef, and diarrheic patients and its potential transmission from cattle to humans through consumption of contaminated beef. The objective of this study was to assess the prevalence and determine the serotypes, genetic relatedness, and antimicrobial resistance of Salmonella in cattle in two local slaughterhouses, in beef at retail shops, and in diarrheic patients in the only hospital in Bishoftu, Ethiopia. Salmonella was detected in 2.5% (6/240) of cattle samples, in 8.7% (11/127) of beef samples, and in 2.3% (5/216) of the diarrheic patients. Four Salmonella serotypes: Salmonella Typhimurium, Salmonella Eastbourne, Salmonella Saintpaul, and Salmonella Cotham were identified. Salmonella Typhimurium and Salmonella Eastbourne were isolated from cattle and beef, whereas Salmonella Saintpaul and Salmonella Cotham were isolated only from diarrheic patients. Except for serotype Salmonella Saintpaul, all isolates were grouped into five pulsotypes, of which two pulsotypes contained isolates from cattle and beef. Isolates from humans represented unique pulsotypes. Among the 22 Salmonella isolates tested, 95.5% were resistant to at least 1 of the 14 antimicrobials tested. Three Salmonella isolates originating from cattle were multidrug resistant. One human isolate was susceptible to all antimicrobials tested. More specifically, resistance to ampicillin, sulfamethoxazole, tetracycline, tigecycline, and trimethoprim were observed. The most frequently observed resistance was to sulfamethoxazole (90.9%, 20/22) followed by trimethoprim (22.7%, 5/22). The study revealed considerable Salmonella contamination of beef at retail shops, antimicrobial resistance to commonly used antimicrobials, and shared genetically similar Salmonella serotypes between cattle and beef; the link with humans could not be established. Still, the findings of Salmonella in cattle and beef, the propensity of transfer of Salmonella from cattle to beef coupled with the common consumption of raw/undercooked beef are likely to pose public health risk in Ethiopia.

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 .

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.

Community perception and knowledge of cystic echinococcosis in the High Atlas Mountains, Morocco.

BACKGROUND: Cystic echinococcosis (CE), a neglected zoonosis caused by the larval stage of the tapeworm Echinococcus granulosus, remains a public health issue in many developing countries that practice extensive sheep breeding. Control of CE is difficult and requires a community-based integrated approach. We assessed the communities' knowledge and perception of CE, its animal hosts, and its control in a CE endemic area of the High Atlas Mountains, Morocco. METHODS: We conducted twenty focus group discussions (FGDs) stratified by gender with villagers, butchers and students in ten Berber villages that were purposefully selected for their CE prevalence. RESULTS: This community considers CE to be a severe and relatively common disease in humans and animals but has a poor understanding of the parasite's life cycle. Risk behaviour and disabling factors for disease control are mainly related to cultural practices in sheep breeding and home slaughtering, dog keeping, and offal disposal at home, as well as in slaughterhouses. Participants in our focus group discussions were supportive of control measures as management of canine populations, waste disposal, and monitoring of slaughterhouses. CONCLUSIONS: The uncontrolled stray dog population and dogs having access to offal (both at village dumps and slaughterhouses) suggest that authorities should be more closely involved in CE control. This study also highlights the need for improved knowledge about the transmission cycle of the parasite among communities and health professionals. Inter-sectoral collaboration between health staff, veterinarians, and social scientists appears to be crucial for sustainable control of this parasitic zoonosis.

Preliminary assessment of the computer-based Taenia solium educational program 'The Vicious Worm' on knowledge uptake in primary school students in rural areas in eastern Zambia.

OBJECTIVE: The zoonotic helminth Taenia solium is endemic in Zambia, causing human (taeniasis and (neuro)cysticercosis) and pig (porcine cysticercosis) diseases with high health, social and economic burdens. We aimed to evaluate the impact of a health educational program intended to lead to powerful and cumulative improvements in knowledge, attitudes and practices that decrease parasite transmission and disease occurrence. METHODS: Half-day health education workshops were conducted in three primary schools in the highly endemic Eastern Province of Zambia, using the computer-based T. solium educational program 'The Vicious Worm'. Questionnaires were administered before and after the educational component to determine the program's impact on knowledge uptake in primary school students. RESULTS: In total, 99 students participated: 38 males and 61 females, with a median age of 14 years (range 10-18 years). Baseline general knowledge of T. solium, including awareness of the different human and pig disease states, and disease diagnosis, treatment and prevention, was quite high (average score 62%) and consistent across all three study areas. Participants' knowledge had significantly increased after the educational component, particularly regarding parasite transmission and disease prevention. CONCLUSION: Preliminary assessment of 'The Vicious Worm' indicates it is an effective tool for the short-term T. solium education of primary school students in Zambia. Follow-up studies are planned to assess the longer term impact of the program on knowledge uptake in the study neighbourhoods. Inclusion of tailored 'The Vicious Worm' educational workshops should be considered in integrated cysticercosis control programs in endemic areas of sub-Saharan Africa.