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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.

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). 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. 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.

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.

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 .

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.

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.

Introduction In this phase 4, multicentre, prospective, non-interventional PIONEER REAL Netherlands study, we assessed clinical outcomes associated with once-daily oral semaglutide use in real-world clinical practice in adults living with type 2 diabetes (T2D) naïve to injectable glucose-lowering medication. Methods Participants initiated on oral semaglutide were followed for 34–44 weeks. Change in glycated haemoglobin (HbA1c) from baseline (BL) to end of study (EOS) was the primary endpoint; secondary endpoints included change in body weight (BW) from BL to EOS, the proportion of participants with HbA1c < 7.0% at EOS and the composite endpoints of HbA1c reduction ≥ 1.0%-points with BW reduction ≥ 3% or ≥ 5% at EOS. Treatment satisfaction was assessed using the Diabetes Treatment Satisfaction Questionnaire (DTSQ status/change). Safety was evaluated in all participants who initiated oral semaglutide treatment. Results Oral semaglutide was initiated in 187 participants; 94.1% completed the study and 78.6% remained on treatment at EOS. At BL, 54.0% of participants were male, mean age was 58.8 years, mean duration of T2D was 8.7 years and mean body mass index was 35.1 kg/m 2 ; mean HbA1c was 8.6% and mean BW was 103.1 kg. Significant improvements from BL to EOS were observed for HbA1c and BW (estimated change [95% confidence interval]: − 1.16%-points [− 1.48 to − 0.85]; p  < 0.0001, and − 5.84 kg [− 6.88 to − 4.80]; p  < 0.0001, respectively). At EOS, 47.5% of participants had an HbA1c level < 7.0%; 41.8% and 35.5% of participants achieved composite endpoints of HbA1c reduction ≥ 1.0%-points plus BW reduction ≥ 3% or ≥ 5%, respectively. DTSQ status and change scores improved by 2.1 ( p  = 0.0003) and 10.8 points ( p  < 0.0001), respectively. Oral semaglutide was easy or very easy to consume for 81.5% of participants. Adverse events were mostly mild/moderate, with gastrointestinal disorders being the most common. Conclusion In this real-world population, we reported clinically significant reductions in HbA1c and BW, improved treatment satisfaction and no new safety concerns. A graphical abstract is available with this article. Clinical Trial Registration NCT04601740. Graphical Abstract

Introduction The study was designed to assess outcomes with once-daily oral semaglutide in adults with type 2 diabetes (T2D) naïve to injectable glucose-lowering agents, in Swedish clinical practice. Methods In this non-interventional, multicentre study, participants initiated oral semaglutide and were followed for 34–44 weeks. The primary endpoint was glycated haemoglobin (HbA 1c ) change from baseline to end of study (EOS). Secondary endpoints included body weight (BW) change from baseline to EOS, proportion of participants achieving HbA 1c  < 7%, and proportion achieving both a HbA 1c reduction ≥ 1% and BW reduction of ≥ 3% or ≥ 5%, at EOS. Participants completed Diabetes Treatment Satisfaction Questionnaires (DTSQ status/change) and a dosing conditions questionnaire. Results A total of 187 participants (mean age 62.5 years) initiated oral semaglutide. Baseline mean HbA 1c and BW were 7.8% ( n  = 177) and 96.9 kg ( n  = 165), respectively. Estimated mean changes in HbA 1c and BW were − 0.88%-points (95% confidence interval [CI] − 1.01 to − 0.75; P  < 0.0001) and − 4.72% (95% CI − 5.58 to − 3.86; P  < 0.0001), respectively. At EOS, 64.6% of participants had HbA 1c  < 7%, and 22.9% achieved HbA 1c reduction of ≥ 1% and BW reduction of ≥ 5%. DTSQ status and change scores improved by 1.44 ( P  = 0.0260) and 12.3 points ( P  < 0.0001), respectively. Oral semaglutide was easy or very easy to consume for 86.4% of participants. Most common adverse events (AEs) were gastrointestinal disorders; nine participants (4.8%) had serious AEs; one (0.5%) experienced severe hypoglycaemia. Conclusion In this real-world study population, we observed significant reductions in HbA 1c and BW in people living with T2D when prescribed semaglutide tablets as part of routine clinical practice in Sweden, with improved treatment satisfaction among participants and no new safety concerns. Trial Registration NCT04601753. Graphical Abstract

Introduction Treatment intensification is often required to attain glycemic targets in people living with type 2 diabetes (T2D) but can introduce regimen complexity and increase medication burden. Whether rates of treatment intensification differ by glucose-lowering medication class is unclear. This study investigated comparative treatment durability of glucagon-like peptide-1 receptor agonists (GLP-1RAs) versus standard T2D treatments, with implications for longitudinal risk mitigation and the need for treatment intensification. Methods This retrospective cohort study used US ambulatory electronic medical record data from January 2006 to November 2021 (covering market availability of first-generation GLP-1RAs) to assess time-to-treatment intensification following initiation of treatment with GLP-1RAs versus sodium–glucose cotransporter-2 inhibitors (SGLT2is), dipeptidyl peptidase-4 inhibitors (DPP-4is), and sulfonylureas (SUs) in 1:1 propensity score-matched adults living with T2D treated with metformin. The primary outcome was the time to treatment intensification (i.e., initiation of a third glucose-lowering medication). Secondary outcomes included change in glycated hemoglobin (HbA 1c ) level and body mass index (BMI) at 12 months after treatment initiation. Results Overall, 59,958 participants were included in this study (GLP-1RA [ n  = 11,933], SGLT2i [ n  = 13,726], DPP-4i [ n  = 14,415], SU [ n  = 19,884]). Initiation of treatment with GLP-1RAs was associated with a significantly lower rate of initiation of a subsequent glucose-lowering medication compared with SGLT2is (hazard ratio [HR]: 0.93 [95% confidence interval, CI, 0.88, 0.97]; p  = 0.001), DPP-4is (HR: 0.77 [95% CI 0.74, 0.81]; p  < 0.001), and SUs (HR: 0.84 [95% CI 0.80, 0.88]; p  < 0.001). After 12 months, GLP-1RA treatment led to a significantly greater reduction in HbA 1c compared with SGLT2i ( p  = 0.005), DPP-4i ( p  < 0.001), and SU ( p  < 0.001) treatment. GLP-1RA treatment was also associated with significantly greater reductions in BMI after 12 months compared with DPP-4i and SU treatment (both p  < 0.001) but not compared with SGLT2i treatment. Conclusion These data suggest that among people living with T2D treated with metformin who require a second glucose-lowering therapy, GLP-1RAs may reduce or delay the need for further treatment intensification versus other standard glucose-lowering therapies.

The cestode 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 ; 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 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 through mathematical modelling approaches. In this paper, we outline developments in control and in particular the use of modelling to help achieve post-2020 targets for control of We discuss the steps involved in improving confidence in the predictive capacities of existing mathematical and computational models on 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 transmission models to inform taeniasis and cysticercosis control strategies.