Use of once-daily oral semaglutide and associated clinical outcomes among adults with type 2 diabetes in routine clinical practice in Canada: A multicentre, prospective real-world study (PIONEER REAL Canada).

AIM: PIONEER REAL Canada examined real-world clinical outcomes associated with the use of once-daily oral semaglutide in adults with type 2 diabetes. MATERIALS AND METHODS: This was a 34- to 44-week, multicentre, prospective, open-label, non-interventional study in adults who were treatment-naive to injectable glucose-lowering medication and initiated oral semaglutide in routine clinical practice. The primary endpoint was the change in glycated haemoglobin (HbA1c) from baseline to the end of the study (EoS). Secondary endpoints assessed at EoS were change from baseline in body weight (BW); the proportion of participants reaching HbA1c levels <7% and the composite endpoints, HbA1c reduction ≥1% point with BW reduction ≥3% and ≥5%; and treatment satisfaction measured using Diabetes Treatment Satisfaction Questionnaires (DTSQ) status and change. Primary analyses were based on the in-study observation period. RESULTS: In total, 182 participants initiated oral semaglutide (mean age, 58.6 years; HbA1c, 8.0%; BW, 93.7 kg). The estimated changes (95% confidence interval) from baseline to EoS in HbA1c and BW were -1.09% points (-1.24, -0.94; p < .0001) and -7.17% (-8.24, -6.11; p < .0001), respectively. At EoS, 53.7% of participants had HbA1c levels <7%; 39.3% and 31.6% reached HbA1c reduction ≥1% point plus BW reduction ≥3% and ≥5%, respectively. Treatment satisfaction significantly increased (DTSQ status, +4.47 points; DTSQ change, 11.83 points; both p < .0001). At EoS, 75.3% of participants remained on oral semaglutide (55.5% received oral semaglutide 14 mg). No new safety signals were identified for oral semaglutide. CONCLUSIONS: In PIONEER REAL Canada, participants treated with oral semaglutide in routine clinical practice experienced clinically relevant reductions in HbA1c and BW and increased treatment satisfaction.

Aggregation of Taenia solium cysticerci in pigs: Implications for transmission and control.

Parasite aggregation within hosts is a fundamental feature of parasite distributions, whereby the majority of parasites are harboured by a minority of hosts. Parasite aggregation can influence their transmission and hence control. In this narrative review, possible sources of aggregation of Taenia solium cysticerci in pigs are discussed, along with implications for control of the parasite. While heavy T. solium infections in pigs could most likely be associated with ingestion of high doses of infective parasite eggs, consistent with coprophagic behaviour of pigs, lighter infections indicate a role of indirect routes of transmission to pigs, mostly from lower infection doses. Light infections are likely to be missed by commonly used diagnostic methods - tongue examination or meat inspection - and end up in the food chain. Hence, they entail a 'hidden' risk and are of a particular public health concern, especially in areas where meat is consumed raw or undercooked. To be effective and sustainable, control strategies against T. solium likely require a broader understanding of, and consideration for parasite transmission dynamics. More importantly, a holistic One Health approach incorporating interventions on humans, pigs and the environment will likely have a larger, more successful and sustainable impact.

TSOL18 vaccine and oxfendazole for control of Taenia solium cysticercosis in pigs: A field trial in endemic areas of Tanzania.

A field trial was conducted in Tanzania to determine the effectiveness of TSOL18 vaccine used concurrently with oxfendazole (OFZ), and of OFZ alone, on T. solium cysticercosis determined by organ and half carcase dissection of slaughter age pigs. This study followed a quasi-experimental group design. Suitable trial sites were randomly allocated to either treatment group T1 (OFZ treatment alone [30mg/kg, Paranthic 10%]) or T2 (TSOL18 [1ml, Cysvax] plus OFZ). Three 4-monthly treatments were administered to eligible pigs. A random selection of pigs were necropsied at baseline and at endline, 2-3.5 months after the final treatment. Additionally, untreated pigs from T1 and T2 areas were necropsied at endline to provide contemporaneous comparisons with T1 and T2 pigs. Baseline prevalence of viable T. solium cysticerci for T1 was 25.5% (Exact 95% CI: 13.9, 40.3; n = 12/47), and for T2 was 12.0% (CI: 6.4, 20.0; n = 12/100). At endline, prevalence was 2.8% for T1 (CI: 0.1, 14.5, n = 1/36) and 0% for T2 (CI: 0, 4.7, n = 0/77). Among untreated pigs, three had viable cysticerci, one from T1 area (12.5%, CI: 0.3, 52.7; n = 1/8) and two from T2 area (5.7%, CI: 0.7, 19.2, n = 2/35). Fisher's exact test showed significant changes in prevalence from baseline to endline in both groups (T1: p = 0.005, T2: p = 0.001). Firth's penalized Maximum Likelihood method suggested the changes were not significant relative to their controls (T1: p = 0.245, T2: p = 0.076). These findings showed a significant reduction in the prevalence of viable cysticerci from baseline to endline after both interventions. However, the changes could not be definitively attributed to the interventions due, in part, to small numbers of control pigs. Concurrent administration of the TSOL18 and OFZ cleared infection among assessed pigs whereas infection remained after treatment with OFZ only. Further studies including larger sample sizes would be required for more definitive conclusions. A One Health approach is recommended for rapid and sustainable impact.

Performance of Ag-ELISA in the diagnosis of Taenia solium cysticercosis in naturally infected pigs in Tanzania.

BACKGROUND: Taenia solium is a zoonotic parasite responsible for neurocysticercosis-a major cause of late-onset acquired epilepsy in humans. Lack of affordable, specific and sensitive diagnostic tools hampers control of the parasite. This study assessed the performance of an antigen detection enzyme-linked immunosorbent assay (Ag-ELISA) in the diagnosis of viable T. solium cysticercosis in naturally infected slaughter-age pigs in an endemic area in Tanzania. METHODS: A total of 350 pigs were bled before they were slaughtered and their carcases examined. Serum was analyzed for circulating antigens by using a monoclonal antibody-based B158/B60 Ag-ELISA. Each carcase was examined for the presence of Taenia hydatigena cysticerci and half carcase musculature together with the whole brain, head muscles, tongue, heart and diaphragm were sliced with fine cuts (< 0.5 cm) to reveal and enumerate T. solium cysticerci. Half carcase dissection can detect at least 84% of infected pigs. Prevalence and their 95% confidence intervals (CI) were calculated in Stata 12. Sensitivity, specificity, predictive values and likelihood ratios were determined. RESULTS: Twenty-nine pigs (8.3%, 95% CI: 5.6-11.7%) had viable T. solium cysticerci while 11 pigs had T. hydatigena cysticerci (3.1%, 95% CI: 1.6-5.5%). No co-infection was observed. Sixty-eight pigs (19.4%, 95% CI: 15.4-20%) tested positive on Ag-ELISA; of these, 24 had T. solium cysticerci and 7 had T. hydatigena cysticerci. Sensitivity and specificity were determined to be 82.7% and 86.3%, respectively. Positive and negative predictive values were 35.2% and 98.2%, respectively. Likelihood ratios for positive and negative Ag-ELISA test results were 6.0 and 0.2, respectively. There was a significant positive correlation between the titre of circulating antigens and intensity of T. solium cysticerci (r(348) = 0.63, P < 0.001). CONCLUSIONS: The Ag-ELISA test characteristics reported in this study indicate that the test is more reliable in ruling out T. solium cysticercosis in pigs, than in confirming it. Hence, a negative result will almost certainly indicate that a pig has no infection, but a positive result should always be interpreted with caution. Estimates of T. solium prevalence based on Ag-ELISA results should, therefore, be adjusted for test performance characteristics and occurrence of T. hydatigena.

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.

Epidemiology of Taenia saginata taeniosis/cysticercosis: a systematic review of the distribution in East, Southeast and South Asia.

BACKGROUND: Taenia saginata is an important zoonotic parasite, causing taeniosis in humans and cysticercosis in bovines, the latter being a significant concern for the global beef industry. Many countries in East, Southeast and South Asia are experiencing rapid economic growth, and an increasing number of people in these countries are dependent on the livestock industry. Currently, however, an overview of the prevalence of T. saginata in this region is lacking. In this review, we analysed the available literature on T. saginata taeniosis and bovine cysticercosis for East, Southeast and South Asia. METHODS: A systematic review was conducted, based on both published and grey literature. Articles published between 1990 and 2017 were mined for information on the occurrence, prevalence, and geographical distribution of T. saginata taeniosis and bovine cysticercosis in East, Southeast and South Asia. RESULTS: The presence of T. saginata was described in 15 of 27 countries of the region, including Afghanistan, Cambodia, China, India, Indonesia, Japan, Lao PDR, Malaysia, Mongolia, Nepal, Pakistan, Philippines, South Korea, Thailand and Vietnam. The only country that reported an absence of T. saginata is Japan, although sporadic reports of imported cases and unconfirmed reports of autochthonous infections were identified. Nationwide surveys of taeniosis with systematic sample collection and high sample numbers were available for Cambodia, China, Lao PDR, and South Korea, although speciation of Taenia was not always performed. Regional prevalence of taeniosis and bovine cysticercosis in endemic regions ranged between 0.02-42.6%, and 0.76-46.7%, respectively. However, data for bovine cysticercosis were only available for five countries (Japan, Lao PDR, Mongolia, Pakistan and Vietnam). CONCLUSIONS: The data indicate a widespread occurrence of T. saginata throughout East, Southeast and South Asia. Identification of Taenia spp. in human infections was frequently not performed, leading to gaps in knowledge about the distribution of human tapeworm infections, mainly in regions where different human Taenia species co-occur. A high prevalence of T. saginata taeniosis and bovine cysticercosis may reflect insufficiencies in sanitation, limited health education standards, and insufficient food safety measures. Therefore, there is a need to improve local surveillance, notification, and overall control systems.

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.

Strategies for tackling Taenia solium taeniosis/cysticercosis: A systematic review and comparison of transmission models, including an assessment of the wider Taeniidae family transmission models.

BACKGROUND: The cestode Taenia solium causes the neglected (zoonotic) tropical disease cysticercosis, a leading cause of preventable epilepsy in endemic low and middle-income countries. Transmission models can inform current scaling-up of control efforts by helping to identify, validate and optimise control and elimination strategies as proposed by the World Health Organization (WHO). METHODOLOGY/PRINCIPAL FINDINGS: A systematic literature search was conducted using the PRISMA approach to identify and compare existing T. solium transmission models, and related Taeniidae infection transmission models. In total, 28 modelling papers were identified, of which four modelled T. solium exclusively. Different modelling approaches for T. solium included deterministic, Reed-Frost, individual-based, decision-tree, and conceptual frameworks. Simulated interventions across models agreed on the importance of coverage for impactful effectiveness to be achieved. Other Taeniidae infection transmission models comprised force-of-infection (FoI), population-based (mainly Echinococcus granulosus) and individual-based (mainly E. multilocularis) modelling approaches. Spatial structure has also been incorporated (E. multilocularis and Taenia ovis) in recognition of spatial aggregation of parasite eggs in the environment and movement of wild animal host populations. CONCLUSIONS/SIGNIFICANCE: Gaps identified from examining the wider Taeniidae family models highlighted the potential role of FoI modelling to inform model parameterisation, as well as the need for spatial modelling and suitable structuring of interventions as key areas for future T. solium model development. We conclude that working with field partners to address data gaps and conducting cross-model validation with baseline and longitudinal data will be critical to building consensus-led and epidemiological setting-appropriate intervention strategies to help fulfil the WHO targets.

Epidemiology of Taenia saginata taeniosis/cysticercosis: a systematic review of the distribution in the Middle East and North Africa.

BACKGROUND: The zoonotic parasite Taenia saginata utilizes bovines as an intermediate host (causing cysticercosis) and humans as the definitive host (causing taeniosis). The public health burden of T. saginata is assumed to be low, but the economic burden is large, due to the resources utilized in the detection and condemnation of infected carcasses and carcass parts. As part of a collaborative effort to synthesize worldwide epidemiological data on this parasite, we present here the results of a systematic review on the distribution of T. saginata taeniosis and bovine cysticercosis in the Middle East and North Africa (MENA). METHODS: Information on the occurrence and prevalence of T. saginata taeniosis and cysticercosis in the MENA region was obtained through a systematic review of published and grey literature, including OIE reports, published between January 1st, 1990 and December 31st, 2017. RESULTS: A total of 63 publications were retrieved across the 21 MENA countries. Taenia saginata taeniosis was reported in 11 of these countries, whereas unspecified taeniosis was reported for a further seven. Microscopy-based prevalence values ranged between 0.02-8.6%. Bovine cysticercosis prevalence estimates based on meat inspection were only reported for Egypt and Israel, with prevalence data ranging between 0.2-20% and 0.1-9.1% for cattle and buffaloes, respectively. The presence of bovine cysticercosis could be confirmed for 10 additional countries through OIE reports. CONCLUSIONS: Human taeniosis occurrence was confirmed for 86% (18/21) of the countries in the MENA region, although in several of these countries the species responsible was not specified. Religious prohibitions on the consumption of pork and the limited extent of pig farming across much of this region, however, suggest that many reported taeniosis cases are likely to be attributable to T. saginata rather than Taenia solium or Taenia asiatica. There was a paucity of data regarding both the prevalence and economic impact of bovine cysticercosis. More detailed epidemiological data on both T. saginata taeniosis and bovine cysticercosis could be obtained by adopting an integrated "One Health" approach, considering the characteristics (e.g. ecosystem related and sociopolitical aspects) of the MENA region. Compared with more conventional approaches, this could lead to an enhanced performance and cost-effectiveness of surveillance systems.