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Background: Taenia solium neurocysticercosis is a zoonotic neglected tropical disease, for which adequate diagnostic management is paramount, especially in patients with active cysts for whom improved and timely management could prove beneficial. Immunodiagnosis can potentially partially mitigate the necessity for neuroimaging, shortening the diagnostic -and treatment- pathway. An up-to-date review of immunological test performance is however lacking. Methodology/Principal findings: Searches were performed in PubMed, EMBASE, Web of Science, and Scopus (up to January 2024), with included records fitting the review scope, i.e. accuracy evaluation of an antibody-/or antigen-detecting immunological test, using serum or urine of humans confirmed via reference standard (i.e. neuroimaging or surgery/biopsy). Record data was assessed, with classification of descriptive data on cyst localization and stage according to a developed confidence scale, and with selection of tests evaluated on a sufficiently high sample size. A QUADAS-2 risk of bias assessment was performed. After screening, 169 records were included for data collection, with 53 records—corresponding to 123 tests- selected for analysis. Absence of data and large data heterogeneity complicated result interpretation. The lentil lectin-bound glycoprotein enzyme-linked immunoelectrotranfser blot seems to fulfill high accuracy standards regarding detection of parenchymal active multiple cysts; also antigen-detecting tests on serum and urine performed well, additionally in detection of extraparenchymal neurocysticercosis. A novel multi-antigen print immunoassay is highly promising, with sensitivity for detection of extraparenchymal and parenchymal active single and multiple cysts of 100.0%, and specificity of 98.5%. Point-of-care tests showed promising results, however require further evaluation in targeted resource-poor settings. Conclusions/Significance: The review highlights the importance of transparent and unambiguous data reporting. With promising immunological tests in development, the challenge before usage in targeted settings will be to perform large-scale evaluations whilst holding into account both optimized test performance and ease of use. Accessibility to validated tests and feasibility of implementation should also be considered. Author summary: Neurocysticercosis is an important, but neglected disease in many low- and middle-income countries. In resource-poor areas, management of the disease is impeded by lack of availability of, and access to, adequate diagnostic techniques. Immunological tests, performed on serum or urine of affected humans, could be tools of interest in improving the diagnostic pathway. This systematic review provides an overview of immunological tests that have been evaluated so far, and especially focusses on test performance in detection of cysts with specific localization, stage and number. Results on test accuracy proved difficult to retrieve from published records. The comparison of obtained test results was exceedingly challenging due to large heterogeneity. With usable data meticulously selected, several known test formats, such as the LLGP-EITB and the antigen ELISA, showed expected performance results, and some novel test formats, such as the multi-antigen print immunoassay, were highly promising. Also, urine-based tests could provide a non-invasive alternative to serum-based tests. Evaluation of immunological tests in non-clinical settings requires a sufficient sample size for further analysis of data. To improve management of the disease in targeted resource-poor settings, immunological test formats will have to comply with high performance and ease-of-use standards, to optimize chances of future implementation. [ABSTRACT FROM AUTHOR]

Porcine cysticercosis (PC) is an important public health problem, especially in sub-Saharan Africa, but limited information is available on the prevalence of infection in pigs entering the food chain. Existing diagnostic methods vary in accuracy and efficiency; whole carcass dissection is the most reliable method but is labour-intensive and destroys the carcass so can only be used in a research setting. Serological tests offer lower specificity, while meat inspection and lingual examination lack sensitivity, hampering accurate estimates and the removal of infected pigs from the food chain. Here, we provide the first estimates of PC prevalence in abattoirs in Rwanda. We use whole carcass dissection to determine the diagnostic accuracy of a commercial antigen-ELISA to estimate the true prevalence of infection across Rwanda and identify Taenia species affecting local pigs. We carried out a cross-sectional survey in 6 abattoirs across Rwanda (n = 744 pigs), with whole carcass dissection of a subset of 67 pigs. Cysts were detected in 20/67 (30%) of carcasses, with >1000 cysts in 9/20 (45%) of infected pigs. All cysts were identified as Taenia solium by PCR-RFLP, with no cysts of Taenia hydatigena found. The antigen-ELISA showed a sensitivity of 90% (95% CI: 68–99) and specificity of 85% (95% CI: 72–94), when compared to dissection. Using these estimates, the true prevalence was calculated as 25–43% in two abattoirs in south-west Rwanda, and 2–3% in the rest of the country. Fewer than half of infected pigs were detected by tongue palpation and post-mortem veterinary inspection. Our data indicate a high prevalence of PC in Rwandan abattoirs. Tongue palpation and veterinary inspections, as currently carried out, have little impact in removing cyst-infested pigs from the food chain. Additional interventions are needed, such as proper pig husbandry, treatment and vaccination against cysticercosis, health education, improved sanitation and hygiene, and improved processing and cooking of meat. Author summary: Porcine cysticercosis is a tapeworm infection with a complex life cycle involving pigs and humans. This parasite is the cause of over a third of cases of acquired epilepsy in regions of the world where sanitation is poor and free-range pigs are reared, and is a public health and economic challenge to consumers and farmers. Our study aimed to estimate the prevalence of tapeworm infection in slaughtered pigs in Rwanda, in order to support disease control. We found that porcine cysticercosis is widespread across the country with a high prevalence in the south and south-west. Pigs with very high numbers of tapeworm cysts were identified and constitute a public health concern to consumers. We showed that the locally available tests for infection such as tongue palpation and veterinary meat inspection are not efficient at preventing infected pigs from reaching consumers. Control of cysticercosis in Rwanda will require further interventions that support hygienic pig production practices and improved pork processing and cooking, ensure appropriate on-farm treatment to stop transmission of porcine cysticercosis and human taeniasis and increase community awareness and behaviour change. [ABSTRACT FROM AUTHOR]

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. Author summary: In this study, we looked at whether a method used to control the spread of the pork tapeworm, a parasite transmitted between pig and people, in Peru could also work in Zambia. The method involved treating people and pigs living near animals infected with tapewormlarvae. We conducted the study in a community where the spread of the parasite via infected meat had been successfully stopped. Every few months, we sampled pigs and people in the area and treated those who were found to be infected or at risk. If a pig tested positive for the parasite, everyone within 50 meters of that pig was treated. Between June 2018 and October 2019, we did four rounds of sampling and treatment. Most people were willing to provide stool samples, and a large percentage of pigs were sampled as well. During treatment, most eligible people and pigs within the affected area received treatment. The study found that people were willing to participate and get treated once the treatment rings were set up. However, there are challenges with accurately diagnosing the parasite in pigs and getting stool samples from people. Before recommending this method to health authorities, further improvements are needed. [ABSTRACT FROM AUTHOR]

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. Author summary: This research assessed the usefulness of a computer-based education tool for Taenia solium taeniasis/cysticercosis to train community health workers in Rwanda. The knowledge of health workers on the disease was assessed before the training, immediately after training, and four weeks later to determine baseline knowledge, knowledge uptake, and retention, respectively. The participants' scores showed a significant improvement in knowledge immediately after the training. Four weeks later, the evaluation showed maintenance of the knowledge for at least the short term. Although digital literacy and lack of smartphones/computer to use the tool was noted as the main challenge, the participants highlighted the structure, completeness, and clarity of the information in the tool, recommending it be used in other areas. [ABSTRACT FROM AUTHOR]

Background: Helminth infections are a global health menace affecting 24% of the world population. They continue to increase global disease burden as their unclear pathology imposes serious challenges to patient management. Neurocysticercosis is classified as neglected tropical disease and is caused by larvae of helminthic cestode Taenia solium. The larvae infect humans and localize in central nervous system and cause NCC; a leading etiological agent of acquired epilepsy in the developing world. The parasite has an intricate antigenic make-up and causes active immune suppression in the residing host. It communicates with the host via its secretome which is complex mixture of proteins also called excretory secretory products (ESPs). Understanding the ESPs interaction with host can identify therapeutic intervention hot spots. In our research, we studied the effect of T. solium ESPs on human macrophages and investigated the post-translation switch involved in its immunopathogenesis. Methodology: T. solium cysts were cultured in vitro to get ESPs and used for treating human macrophages. These macrophages were studied for cellular signaling and miR expression and quantification at transcript and protein level. Conclusion: We found that T. solium cyst ESPs treatment to human macrophages leads to activation of Th2 immune response. A complex cytokine expression by macrophages was also observed with both Th1 and Th2 cytokines in milieu. But, at the same time ESPs modulated the macrophage function by altering the host miR expression as seen with altered ROS activity, apoptosis and phagocytosis. This leads to activated yet compromised functional macrophages, which provides a niche to support parasite survival. Thus T. solium secretome induces Th2 phenomenon in macrophages which may promote parasite's survival and delay their recognition by host immune system. Author summary: This article discusses the research conducted on the effect of Taenia solium excretory secretory proteins (ESPs) on human macrophages and its role in the immunopathogenesis of Neurocysticercosis (NCC). NCC is a neglected tropical disease caused by larvae of T. solium, which infect humans and localizes in the central nervous system. The larvae cause NCC, a leading cause of acquired epilepsy in the developing world. The study found that T. solium ESPs induce a Th2 immune response in macrophages, which may promote parasite survival and delay their recognition by the host immune system. The research further showed that ESPs modulate macrophage function by altering host miR expression, leading to activated yet compromised functionality that provides a niche for parasite survival. This study provides insights into the interaction of ESPs with the host, revealing therapeutic intervention hot spots to manage NCC and other helminthic infections. In the absence of suitable animal model for NCC, our study elucidates important and novel finding of parasite mediated suppression of host immune system. [ABSTRACT FROM AUTHOR]

Background: Several studies on Taenia solium taeniosis / cysticercosis (TSTC) have been conducted in Zambia. However, none has assessed community knowledge, attitudes and practices related to TSTC and epilepsy. Methods: A community-based cross-sectional study was conducted between November and December 2022. The design consisted of a questionnaire-based survey conducted in each of the 25 purposely selected villages in Chiparamba Rural Health Centre (RHC) catchment area in Chipata district of the Eastern Province. Results: A total of 588 participants comprising 259 (44%) males and 329 (56%) females with median age of 42 years (range 17 to 92 years) were interviewed. Awareness of the signs and symptoms of taeniosis and human cysticercosis (HCC), including transmission and prevention measures was very low. Whilst the majority had heard about epilepsy, they were not able to link HCC to epilepsy. Most participants were aware of cysticerci in pigs (PCC) including its predilection sites but were not aware of mode of transmission and prevention measures. The pork meat inspection by trained professionals was also not a common practice in the area. Risk perception of T. solium infections was thus very low. Overall knowledge, attitude and practice scores related to T. solium infections and to epilepsy were very low with median scores of 0.38 (IQR 0.25–0.54) for knowledge, 0.25 (0.25–0.50) for attitudes, and 0.31 (0.25–0.44) for practices. Males had better knowledge on TSTC (median = 0.42, p = 0.017, r = 0.098) and better practice scores (median = 0.38, p = < 0.001, r = 0.154) compared to females though the effect size was small. With regards to sanitation and hygiene washing with soap and water was reported by many but only few had a hand washing facility near their latrines. Conclusion: The study shows overall poor knowledge, attitudes and practices related to TSTC among the community of Chiparamba RHC in Chipata district of the Eastern Province of Zambia. This poses a serious challenge for control and elimination of T. solium infections and thus efforts to improve knowledge, attitudes and practices should be made using a One Health approach for the control and elimination of TSTC. Educational programs about TSTC transmission, signs and symptoms, prevention, management and control need to be scaled up in the study area and Zambia as a whole. Author summary: Taenia solium taeniosis / cysticercosis (TSTC) is endemic in Zambia. We aimed at assessing knowledge, attitudes and practices (KAP) related to TSTC and epilepsy in a community setting in Chiparamba area of Chipata district of the Eastern Province of Zambia. Understanding KAP is important in designing and implementing public health interventions for control and eradication of TSTC in a community. We found generally poor KAP related to TSTC among the community in our study area. This lack of knowledge about TSTC infections can lead to behaviours that facilitate the transmission and maintenance of T. solium infections and could hinder efforts to control the most preventable cause of epilepsy in the sub-Saharan African region. More efforts to improve KAP using a One Health approach for the control and elimination of TSTC are therefore required in Zambia. [ABSTRACT FROM AUTHOR]

Cysticercosis is a neglected tropical disease caused by the larval stage of the zoonotic tapeworm (Taenia solium). While there is a clear spatial component in the occurrence of the parasite, no geostatistical analysis of active human cysticercosis has been conducted yet, nor has such an analysis been conducted for Sub-Saharan Africa, albeit relevant for guiding prevention and control strategies. The goal of this study was to conduct a geostatistical analysis of active human cysticercosis, using data from the baseline cross-sectional component of a large-scale study in 60 villages in Burkina Faso. The outcome was the prevalence of active human cysticercosis (hCC), determined using the B158/B60 Ag-ELISA, while various environmental variables linked with the transmission and spread of the disease were explored as potential explanatory variables for the spatial distribution of T. solium. A generalized linear geostatistical model (GLGM) was run, and prediction maps were generated. Analyses were conducted using data generated at two levels: individual participant data and grouped village data. The best model was selected using a backward variable selection procedure and models were compared using likelihood ratio testing. The best individual-level GLGM included precipitation (increasing values were associated with an increased odds of positive test result), distance to the nearest river (decreased odds) and night land temperature (decreased odds) as predictors for active hCC, whereas the village-level GLGM only retained precipitation and distance to the nearest river. The range of spatial correlation was estimated at 45.0 [95%CI: 34.3; 57.8] meters and 28.2 [95%CI: 14.0; 56.2] km for the individual- and village-level datasets, respectively. Individual- and village-level GLGM unravelled large areas with active hCC predicted prevalence estimates of at least 4% in the south-east, the extreme south, and north-west of the study area, while patches of prevalence estimates below 2% were seen in the north and west. More research designed to analyse the spatial characteristics of hCC is needed with sampling strategies ensuring appropriate characterisation of spatial variability, and incorporating the uncertainty linked to the measurement of outcome and environmental variables in the geostatistical analysis. Trial registration: ClinicalTrials.gov; NCT0309339. Author summary: Cysticercosis is a serious, yet neglected disease caused by the larval stage of a zoonotic tapeworm, prevalent in many developing countries, including Burkina Faso. Being able to predict where the disease occurs is essential for running targeted prevention and control activities. In our study, we aimed to describe whether human cysticercosis cases in three provinces in Burkina Faso were clustered, and investigated whether there was a link between this clustering and some land and weather variables. Finally, we aimed to generate high-resolution prediction maps for the occurrence of the infection. We found that there was clustering at 45 meters for the individual- and 28.2 km for the village-level datasets, respectively. Increasing rainfall and proximity to a river were linked with this clustering. The generated prediction maps indicated there were important cysticercosis hotspots in the study area, especially in the extreme south and north-west, where the disease is thought to be more important. Further research should expand the use of spatial techniques to predict the occurrence of cysticercosis, the results of which can aid in the design of intervention programmes. [ABSTRACT FROM AUTHOR]

Background: The morbidity and mortality of extraparenchymal neurocysticercosis (EP-NC) remain high and effectiveness of current medical treatment is suboptimal. Various factors have been implicated in the severity of EP-NC and in the poor response to treatment, but the possible role of host immune and endocrine systems has not yet been examined thoroughly. Methodology/Principal findings: 42 participants with EP-NC before receiving standard treatment and 25 healthy controls were included in the study. Treatment response was assessed by comparing pre/post treatment parasite volumes from 3D MRI. Prior to treatment among participants with EP-NC, specific stimulation induced an increased specific proliferative response accompanied by a significant increase in IL-4, NK, NKT, Bregs and Tregs cells, whereas in healthy controls, specific stimulation induced a significant increase in IL-1β, IL-5, CCL5, IL-6, TNF-α, NK and Bregs cells. Significant differences between participants with EP-NC and healthy controls in the specific inflammatory response were observed. Participants with EP-NC prior to treatment had significantly weaker responses of proinflammatory cytokines (IL-6, TNF-α) and NK cells, and stronger IL-4 response. Anthelmintic treatment did not promote significant peripheral immunological changes at any time, although inflammation was sustained in the cerebrospinal fluid. Serum estradiol concentration significantly decreased after anthelmintic treatment among males, and cortisol correlated negatively with IL-6 and positively with IFN-γ levels. No pre-treatment immunologic or endocrinologic parameters were significantly associated with response to treatment. Conclusion/Significance: Prior to anthelmintic treatment, EP-NC was characterized by low lymphocyte reactivity accompanied by a regulatory response, which may be involved in the lack of peripheral immunological changes during and after treatment, although a central inflammatory response was present. This weak specific peripheral response could favor the chronicity of the infection and the poor response to treatment. Our findings highlight the need for new anti-inflammatory treatment focused on the central nervous system with less systemic immunosuppressive effects. Author summary: Neurocysticercosis is a central nervous system infection with the helminth Taenia solium in its larval stage. It is a marker of poverty and remains endemic in countries of Latin America, Africa, and Asia. The severity of neurocysticercosis and the prognosis of patients depend on the location of the parasites. Extraparenchymal infection involving the subarachnoid and/or ventricular space is associated with high morbidity and mortality and a suboptimal response to current anthelminthic treatment regimens. We examined peripheral immunological parameters and hormones of 42 participants with extraparenchymal neurocysticercosis before and after treatment, and their associations with subsequent treatment response. Prior to treatment, compared with healthy controls, there was low lymphocyte reactivity with a regulatory response, which may explain the lack of peripheral immunological changes during and after treatment. This weak specific peripheral response could favor the chronicity of the infection and the poor response to treatment and should be considered in research to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Taenia solium is a tapeworm that causes taeniosis in humans and cysticercosis in humans and pigs. Within Eastern and Southern Africa (ESA), information on the presence of human taeniosis and cysticercosis seems scarce. This systematic review aimed to describe the current information available and gaps in the epidemiology of human T. solium infections in ESA. Methods/Principle findings: Scientific literature published between 1st January 2000 and 20th June 2022 in international databases [MEDLINE (Ovid), Embase (Ovid), Global Health (Ovid), Scopus (Elsevier), African Index Medicus (via WHO Global Index Medicus), and Open Grey] was systematically reviewed for ESA. The study area included 27 countries that make up the ESA region. Information on either taeniosis, cysticercosis or NCC was available for 16 of 27 countries within the region and a total of 113 reports were retained for the review. Most case reports for cysticercosis and NCC were from South Africa, while Tanzania had the most aggregated cysticercosis reports. Eleven countries reported on NCC with seven countries reporting data on NCC and epilepsy. Unconfirmed human T. solium taeniosis cases were reported in nine countries while two countries (Madagascar and Zambia) reported confirmed T. solium cases. The cysticercosis seroprevalence ranged between 0.7–40.8% on antigen (Ag) ELISA and between 13.1–45.3% on antibody (Ab) ELISA. Based on immunoblot tests the Ab seroprevalence was between 1.7–39.3%, while the proportion of NCC-suggestive lesions on brain CT scans was between 1.0–76% depending on the study population. The human taeniosis prevalence based on microscopy ranged between 0.1–14.7%. Based on Copro Ag-ELISA studies conducted in Kenya, Rwanda, Tanzania, and Zambia, the highest prevalence of 19.7% was reported in Kenya. Conclusions: Despite the public health and economic impact of T. solium in ESA, there are still large gaps in knowledge about the occurrence of the parasite, and the resulting One Health disease complex, and monitoring of T. solium taeniosis and cysticercosis is mostly not in place. Author summary: Taenia solium is a tapeworm that causes three diseases, taeniosis in humans and cysticercosis in humans and pigs. Neurocysticercosis, which occurs when the central nervous system is involved has been associated with up to 57% of epilepsy cases in sub–Saharan Africa. Diagnosing neurocysticercosis among people with epilepsy is vital to prevent further morbidity and mortality from the disease as well as to reduce the negative socio-cultural beliefs associated with epilepsy. Within Eastern and Southern Africa, there are many countries in which information on the presence of human taeniosis, cysticercosis and neurocysticercosis seems scarce. This systematic review aimed to describe the current information available and gaps in the epidemiology of human T. solium infections in Eastern and Southern Africa. We found that Information on either taeniosis, cysticercosis or NCC was available only for 16 of 27 countries within the region. We also found that most of the studies on T. solium taeniosis, cysticercosis and neurocysticercosis within the region have been done in Kenya, Madagascar, Mozambique, Rwanda, South Africa, Tanzania and Zambia. Understanding the epidemiology of T. solium infections is essential for monitoring, prevention and control of the disease complex in a One Health approach. [ABSTRACT FROM AUTHOR]

Background: Neurocysticercosis (NCC) is common among people with epilepsy in low-resource settings. Prevalence of NCC and radiological characteristics of patients with NCC vary considerably even within small areas but differences have been poorly characterized so far. Methods: We conducted a cross-sectional study between August 2018 and April 2020 in three district hospitals in southern Tanzania (Ifisi, Tukuyu and Vwawa). Patients with and without epileptic seizures were included in this study. All patients were tested with a novel antibody-detecting point-of-care test for the diagnosis of Taenia solium cysticercosis. All test positives and a subset of test negatives had a further clinical work-up including medical examination and computed tomography of the brain. NCC was defined according to the Del Brutto criteria. We assessed epidemiological, clinical and radiological characteristics of patients with NCC by presence of epileptic seizures and by serology status. Results: In all three district hospitals, more than 30% of all people with epileptic seizures (PWE) had NCC lesions in their brain (38% in Vwawa, 32% in Tukuyu and 31% in Ifisi). Most PWE with NCC had multiple lesions and mostly parenchymal lesions (at least 85%). If patients were serologically positive, they had in the median more lesions than serologically negative patients (15 [interquartile range 8–29] versus 5 [1.8–11]), and only serologically positive patients had active stage lesions. Furthermore, serologically positive PWE had more lesions than serologically positive people without epileptic seizures (10.5 [7–23]), and more often had active lesions. PWE diagnosed with NCC (n = 53) were older, and more commonly had focal onset seizures (68% versus 44%, p = 0.03) and headache episodes (34% versus 14%, p = 0.06), which were also stronger than in PWE without NCC (p = 0.04). Conclusion: NCC is common among PWE. A combination of clinical and serological factors could help to establish an algorithm to identify patients potentially suffering from active NCC, who benefit from further clinical investigation including neuroimaging. Author summary: Neurocysticercosis (NCC) is a neglected tropical disease caused by the pork tapeworm Taenia solium. The disease remains often silent for years, and some patients never experience any symptoms at all. If the disease becomes symptomatic, symptoms are manifold but most commonly patients suffer from epileptic seizures or headache. Symptoms depend on the location, number and stage of the NCC lesions. Radiological features of NCC differ between world regions and are still understudied for African populations. In this study, we describe radiological but also clinical features of NCC patients with and without epileptic seizures. We found that around one third of patients with epileptic seizures had NCC typical lesions in their brain. Most patients had multiple parenchymal lesions–patients with epileptic seizures had on average more lesions than asymptomatic patients. Patients with epileptic seizures and NCC more commonly had focal onset seizure than patients with epileptic seizures without NCC. [ABSTRACT FROM AUTHOR]

Background: Neurocysticercosis (NCC), a zoonotic disease caused by the pork tapeworm T. solium, represents one of the most common causes of secondary epilepsy but remains often undiagnosed due to lack of awareness and diagnostic facilities. Methodology: We pooled data from four cross-sectional studies on epilepsy and NCC in eastern Africa. Study sites were in Uganda, Malawi and in Tanzania (Dar es Salaam and Haydom). The study in Uganda and Malawi were community-based, the two studies in Tanzania were hospital-based. The same questionnaire was used for assessment of clinical characteristics of patients with epilepsy. Computed tomography (CT) scans and serological testing were performed in order to diagnose NCC. Results: Overall, 1,179 people with epilepsy were included in our analysis. Of those, 941 PWE underwent CT scanning and were pooled for NCC analysis. Seventy patients were diagnosed with NCC, but NCC prevalence differed considerably between sites ranging from 2.0% (95%CI 0.4% to 3.6%) in Dar es Salaam to 17.5% (95%CI 12.4% to 22.6%) in Haydom. NCC prevalence did not show any association with sex but increased with age and was higher in rural than urban settings. In addition, being a farmer, non-Muslim, eating pork and living with pigs close by was associated with a higher NCC prevalence. PWE with NCC experienced their first epileptic seizure around 3 years later in life compared to PWE without NCC and their epileptic seizures seemed to be better controlled (p<0.001). There was no difference between focal onset seizures and focal signs on neurological examination in both groups (p = 0.49 and p = 0.92, respectively). The rT24H-EITB had a sensitivity for the detection of NCC of 70% (95% confidence interval [CI] 51 to 84%), the LLGP of 76% (95%CI 58 to 89%) and the antigen ELISA of 36% (95% CI 20 to 55%). Conclusions: NCC is prevalent among PWE in eastern Africa, although it may not be as common as previously stated. Demographic characteristics of PWE with NCC differed from those without NCC, but semiological characteristics and results on neurological examination did not differ compared to PWE without NCC. Interestingly, seizures seemed to be less frequent in PWE with NCC. Being aware of those differences and similarities may help triaging PWE for neuroimaging in order to establish a diagnosis of NCC. Author summary: Neurocysticercosis is a neglected zoonotic disease caused by the pork tapeworm Taenia solium. Patients with neurocysticercosis show a wide range of symptoms, from asymptomatic to severely affected by epileptic seizures, progressive headache or focal neurological deficits. Epileptic seizures are particularly common and up to 30% of people with epilepsy have neurocysticercosis in areas endemic for Taenia solium. The disease is often undiagnosed in Africa because of a lack of diagnostic opportunities (serological tests and neuroimaging). Furthermore, symptoms are too unspecific to diagnose patients solely based on clinical characteristics. Moreover, radiological features of neurocysticercosis differ between continents and have not been described yet for African populations. In this study, for the first time, we describe radiological but also clinical features of patients with epilepsy and neurocysticercosis in eastern Africa. We found that in Tanzania, Malawi and Uganda, neurocysticercosis is common in people with epilepsy although less common than previously reported. Also, most patients with neurocysticercosis have multiple parenchymal lesions and clinical features of people with epilepsy and neurocysticercosis do not differ substantially from people with epilepsy without neurocysticercosis. [ABSTRACT FROM AUTHOR]

Background: Epilepsy and neurocysticercosis (NCC) prevalence estimates in sub-Saharan Africa are still scarce but show important variation due to the population studied and different screening and diagnosis strategies used. The aims of this study were to estimate the prevalence of epileptic seizures and epilepsy in the sampled population, and the proportion of NCC among people with epilepsy (PWE) in a large cross-sectional study in a rural district of southern Malawi. Methods: We conducted a community-based door-to-door screening study for epileptic seizures in Balaka, Malawi between October and December 2012. Past epileptic seizures were reported through a 15-item questionnaire answered by at least one person per household generating five major criteria. People who screened positive were further examined by a neurologist to establish diagnosis. Patients diagnosed with epilepsy were examined and offered Taenia solium cyst antigen and antibody serological tests, and a CT scan for the diagnosis of NCC. Results: In total, screening information on 69,595 individuals was obtained for lifetime occurrence of epileptic seizures. 3,100 (4.5%) participants screened positive, of whom 1,913 (62%) could be followed-up and underwent further assessment. Lifetime prevalence was 3.0% (95% Bayesian credible interval [CI] 2.8 to 3.1%) and 1.2% (95%BCI 0.9 to 1.6%) for epileptic seizures and epilepsy, respectively. NCC prevalence among PWE was estimated to be 4.4% (95%BCI 0.8 to 8.5%). A diagnosis of epilepsy was ultimately reached for 455 participants. Conclusion: The results of this large community-based study contribute to the evaluation and understanding of the burden of epilepsy in the population and of NCC among PWE in sub-Saharan Africa. Author summary: Epilepsy is more common in low-income and middle-income countries than in high-income countries. One of the reasons for this is that risk factors for acquired epilepsy such as Taenia solium cysticercosis are more common in these countries. In this study we conducted a screening for epileptic seizures among nearly 70,000 people of rural Balaka district of Malawi. We found that around 3 percent of people have ever experienced an epileptic seizure and that 1 percent of people suffer from epilepsy. The screening questionnaire that we used was quite accuracte, and the more criteria for screening positive were fulfilled, the more likely it was that the person has ever experienced an epileptic seizure. Among the patients with epilepsy, around 5% also had neurocysticercosis typical lesions in their brain. [ABSTRACT FROM AUTHOR]

Background: Taenia solium is the most significant global foodborne parasite and the leading cause of preventable human epilepsy in low and middle-income countries in the form of neurocysticercosis. Objectives: This scoping review aimed to examine the methodology of peer-reviewed studies that estimate the burden of T. solium using disability-adjusted life years. Eligibility criteria: Studies must have calculated disability-adjusted life years relating to T. solium. Charting methods: The review process was managed by a single reviewer using Rayyan. Published data relating to disease models, data sources, disability-adjusted life years, sensitivity, uncertainty, missing data, and key limitations were collected. Results: 15 studies were included for review, with seven global and eight national or sub-national estimates. Studies primarily employed attributional disease models that relied on measuring the occurrence of epilepsy before applying an attributable fraction to estimate the occurrence of neurocysticercosis-associated epilepsy. This method relies heavily on the extrapolation of observational studies across populations and time periods; however, it is currently required due to the difficulties in diagnosing neurocysticercosis. Studies discussed that a lack of data was a key limitation and their results likely underestimate the true burden of T. solium. Methods to calculate disability-adjusted life years varied across studies with differences in approaches to time discounting, age weighting, years of life lost, and years of life lived with disability. Such differences limit the ability to compare estimates between studies. Conclusions: This review illustrates the complexities associated with T. solium burden of disease studies and highlights the potential need for a burden of disease reporting framework. The burden of T. solium is likely underestimated due to the challenges in diagnosing neurocysticercosis and a lack of available data. Advancement in diagnostics, further observational studies, and new approaches to parameterising disease models are required if estimates are to improve. Author summary: Taenia solium is a parasitic worm of people and pigs. It is the most significant global foodborne parasite and causes neurocysticercosis, the leading cause of preventable human epilepsy in low and middle-income countries. Due to this significance, many people have attempted to estimate the burden of disease of T. solium. The disability-adjusted life year is the most common method for measuring burden of disease and combines the number of years of life lost with the number of years of life lived with disability due to an illness. This review found that many published studies probably underestimate the true burden of disease due to the challenges in diagnosing neurocysticercosis. If estimates are to become more accurate there must be further research into the epidemiology of T. solium and new approaches to disease modelling. Current estimates can be difficult to compare and a reporting framework for burden of disease studies may increase their utility by facilitating subsequent use and interpretation of different approaches. [ABSTRACT FROM AUTHOR]

Background: Neurocysticercosis (NCC) is the infection of the human central nervous system (CNS) by Taenia solium larvae that cause significant neurological morbidity. Studies on NCC pathophysiology, host-parasite interactions or therapeutic agents are limited by the lack of suitable animal models. We have previously reported that carotid injection of activated T. solium oncospheres directs parasites into the CNS and consistently reproduces NCC. This study assessed the minimal dose required to consistently obtain NCC by intracarotid oncosphere injection and compared antigen and antibody response profiles by dose-group. Methods/Principal findings: Three groups of pigs were infected with either 2500 (n = 10), 5000 (n = 11), or 10000 (n = 10) oncospheres. Two pigs died during the study. Necropsy exam at day 150 post-infection (PI) demonstrated viable NCC in 21/29 pigs (72.4%), with higher NCC rates with increasing oncosphere doses (4/9 [44.4%], 9/11 [81.8%] and 8/9 [88.9%] for 2500, 5000, and 10000 oncospheres respectively, P for trend = 0.035). CNS cyst burden was also higher in pigs with increasing doses (P for trend = 0.008). Viable and degenerated muscle cysticerci were also found in all pigs, with degenerated cysticerci more frequent in the 2500 oncosphere dose-group. All pigs were positive for circulating parasite antigens on ELISA (Ag-ELISA) from day 14 PI; circulating antigens markedly increased at day 30 PI and remained high with plateau levels in pigs infected with either 5000 or 10000 oncospheres, but not in pigs infected with 2500 oncospheres. Specific antibodies appeared at day 30 PI and were not different between dose-groups. Conclusion/Significance: Intracarotid injection of 5000 or more oncospheres produces high NCC rates in pigs with CNS cyst burdens like those usually found in human NCC, making this model appropriate for studies on the pathogenesis of NCC and the effects of antiparasitic treatment. Author summary: Neurocysticercosis (NCC) is the infection of the central nervous system (CNS) with Taenia solium larvae and is considered a neglected disease that causes significant neurological morbidity in humans. Animal models are essential to better understand the pathophysiological processes that occur during NCC infection, disease progression and to evaluate the effects of antiparasitic treatment. Here, we demonstrated that by injecting 5000 or more activated T. solium oncospheres into the carotid artery of pigs we consistently reproduced NCC in a number that closely resemble human infection. All cysticerci found in the CNS were apparently viable, whereas in the musculature viable and degenerated cysticerci were found. Serum antigens in experimentally infected pigs were detected as early as 14 days post–infection and remained high in NCC pigs until necropsy. Histological analysis of brain cysticerci showed different degrees of inflammatory cell infiltration adjacent to the cyst wall, mostly composed of eosinophils, lymphocytes, and macrophages, whereas most of the cysticerci were apparently intact with cyst wall and neck without damage. Our findings demonstrated that the intracarotid pig model is suitable for studies on the pathogenesis and antiparasitic treatment in NCC. [ABSTRACT FROM AUTHOR]

Background: Antigen tests for diagnosis and disease monitoring in some types of neurocysticercosis (NCC) are useful but access to testing has been limited by availability of proprietary reagents and/or kits. Methods/Principal findings: Three previously identified IgM-secreting hybridomas whose IgM products demonstrated specificity to Taenia solium underwent variable heavy and light chain sequencing and isotype conversion to mouse IgG. Screening of these recombinantly expressed IgG anti-Ts hybridomas, identified one (TsG10) with the highest affinity to crude Taenia antigen. TsG10 was then used as a capture antibody in a sandwich antigen detection immunoassay in combination with either a high titer polyclonal anti-Ts antibody or with biotinylated TsG10 (termed TsG10*bt). Using serum, plasma, and CSF samples from patients with active NCC and those from NCC-uninfected patients, ROC curve analyses demonstrated that the TsG10-TsG10-*bt assay achieved a 98% sensitivity and 100% specificity in detecting samples known to be antigen positive and outperformed the polyclonal based assay (sensitivity of 93% with 100% specificity). By comparing levels of Ts antigen (Ag) in paired CSF (n = 10) or plasma/serum (n = 19) samples from well-characterized patients with extra-parenchymal NCC early in infection and at the time of definitive cure, all but 2 (1 from CSF and 1 from plasma) became undetectable. There was a high degree of correlation (r = 0.98) between the Ag levels detected by this new assay and levels found by a commercial assay. Pilot studies indicate that this antigen can be detected in the urine of patients with active NCC. Conclusions/Significance: A newly developed recombinant monoclonal antibody-based Ts Ag detection immunoassay is extremely sensitive in the detection of extra-parenchymal NCC and can be used to monitor the success of treatment in the CSF, serum/plasma and urine. The ability to produce recombinant TsG10 at scale should enable use of this antigen detection immunoassay wherever NCC is endemic. Clinical Trial Registration: ClinicalTrials.gov Identifiers: NCT00001205 - & NCT00001645. Author summary: Neurocysticercosis, an NTD caused by the helminth Taenia solium, is a major cause of neurologic symptoms in endemic areas. Diagnosis rests upon imaging of the central nervous system, which is not always available, and is not specific in many cases. Testing for T. solium antigen in the peripheral blood and cerebral spinal fluid of patients with a high burden of neurocysticercosis has already been shown to have a high utility in assisting in diagnosis and following over the course of therapy, particularly for extra parenchymal disease. Here we describe a capture ELISA assay (called TsG10) with high sensitivity and specificity for detecting T. solium antigen that was produced recombinantly and can be easily transitioned into a lateral flow assay for point of care testing. We also demonstrate the utility in following this antigen assay over the course of treatment for patients with extra-parenchymal disease. Additionally, we publish the antibody sequence for use by any lab with the interest and capabilities of performing this test, without the need for access to a hybridoma. [ABSTRACT FROM AUTHOR]

Background: Infections with the tapeworm Taenia solium (taeniosis and cysticercosis) are Neglected Tropical Diseases (NTD) highly endemic in Madagascar. These infections are however underdiagnosed, underreported and their burden at the community level remains unknown especially in rural remote settings. This study aims at assessing the prevalence of T. solium infections and associated risk factors in twelve remote villages surrounding Ranomafana National Park (RNP), Ifanadiana District, Madagascar. Methodology: A community based cross-sectional survey was conducted in June 2016. Stool and serum samples were collected from participants. Tapeworm carriers were identified by stool examination. Taenia species and T. solium genotypes were characterised by PCR and sequencing of the mitochondrial cytochrome c oxidase subunit 1 (cox1) gene. Detection of specific anti-cysticercal antibodies (IgG) or circulating cysticercal antigens was performed by ELISA or EITB/Western blot assays. Principal findings: Of the 459 participants with paired stool and blood samples included ten participants from seven distinct villages harbored Taenia spp. eggs in their stools samples DNA sequencing of the cox1 gene revealed a majority of T. solium Asian genotype (9/10) carriage. The overall seroprevalences of anti-cysticercal IgGs detected by ELISA and EITB were quite similar (27.5% and 29.8% respectively). A prevalence rate of 12.4% of circulating cysticercal antigens was observed reflecting cysticercosis with viable cysts. Open defecation (Odds Ratio, OR = 1.5, 95% CI: 1.0–2.3) and promiscuity with households of more than 4 people (OR = 1.9, 95% CI: 1.1–3.1) seem to be the main risk factors associated with anticysticercal antibodies detection. Being over 15 years of age would be a risk factor associated with an active cysticercosis (OR = 1.6, 95% CI: 1.0–2.7). Females (OR = 0.5, 95% CI: 0.3–0.9) and use of river as house water source (OR = 0.3, 95% CI: 0.1–1.5) were less likely to have cysticercosis with viable cysts. Conclusions/Significance: This study indicates a high exposure of the investigated population to T. solium infections with a high prevalence of cysticercosis with viable cysts. These data can be useful to strengthen public health interventions in these remote settings. Author summary: Taenia solium infections in humans (taeniosis and neurocysticercosis) and in pigs (cysticercosis) are endemic in Madagascar presenting a significant public health burden. Neurocysticercosis with localization of the parasite in the Central Nervous System is the most severe and frequent form of parasitic brain diseases in humans and responsible of thousands of worldwide deaths per year. Madagascar is a T. solium endemic country where poor sanitation, free roaming pigs and outdoor defecation are common, and maintain the parasite transmission cycle. Little information is available regarding taeniosis/cysticercosis epidemiology in Madagascar. We carried out a community-based study to investigate the prevalence of human taeniosis/cysticercosis and associated risk factors in 12 rural remote villages of Ranomafana and Kelilalina townships (Ifanadiana district, Madagascar). Our results reveal that in 7/12 villages investigated, a high number of participants had teaniosis. Moreover, a high number of active cysticercosis cases were detected. Open defecation and promiscuity were seemed to be the main risk factors associated to T. solium infections. The results of this study will be useful to guide interventions in these remote settings surrounding the Ranomafana National Park. [ABSTRACT FROM AUTHOR]

Combined community health programs aiming at health education, preventive anti-parasitic chemotherapy, and vaccination of pigs have proven their potential to regionally reduce and even eliminate Taenia solium infections that are associated with a high risk of neurological disease through ingestion of T. solium eggs. Yet it remains challenging to target T. solium endemic regions precisely or to make exact diagnoses in individual patients. One major reason is that the widely available stool microscopy may identify Taenia ssp. eggs in stool samples as such, but fails to distinguish between invasive (T. solium) and less invasive Taenia (T. saginata, T. asiatica, and T. hydatigena) species. The identification of Taenia ssp. eggs in routine stool samples often prompts a time-consuming and frequently unsuccessful epidemiologic workup in remote villages far away from a diagnostic laboratory. Here we present "mail order" single egg RNA-sequencing, a new method allowing the identification of the exact Taenia ssp. based on a few eggs found in routine diagnostic stool samples. We provide first T. solium transcriptome data, which show extremely high mitochondrial DNA (mtDNA) transcript counts that can be used for subspecies classification. "Mail order" RNA-sequencing can be administered by health personnel equipped with basic laboratory tools such as a microscope, a Bunsen burner, and access to an international post office for shipment of samples to a next generation sequencing facility. Our suggested workflow combines traditional stool microscopy, RNA-extraction from single Taenia eggs with mitochondrial RNA-sequencing, followed by bioinformatic processing with a basic laptop computer. The workflow could help to better target preventive healthcare measures and improve diagnostic specificity in individual patients based on incidental findings of Taenia ssp. eggs in diagnostic laboratories with limited resources. Author summary: Taeniasis is an infection of the intestine with tapeworms such as Taenia saginata (beef tapeworm), Taenia solium (pork tapeworm), or Taenia asiatica (Asian tapeworm). In the case of pork tapeworm in particular, infected individuals excrete thousands of eggs in their feces, which can cause cysticercosis if ingested by mouth and develop into larvae. Infection can occur through contaminated vegetables, but also by unwashed hands that had contact with Taenia eggs, including auto-infection. The larval cysts are deposited throughout the body, including the brain (neural cysticercosis), which is a common cause of epilepsy worldwide. Stool microscopy is the standard method for detecting taeniasis, but it cannot distinguish between infection with the beef and the more dangerous pork tapeworm. We have now developed a next-generation sequencing method that allows us to determine the genetic code of the tapeworm's mitochondrial DNA from just two eggs in a stool sample. The sequence obtained makes it possible to uniquely identify Taenia subspecies, treat patients appropriately, and inform public health efforts of endemic regions in order to eradicate this infection, as proposed by WHO. [ABSTRACT FROM AUTHOR]

Neurocysticercosis (NCC), the infection of the nervous system by the cystic larvae of Taenia solium, is a highly pleomorphic disease because of differences in the number and anatomical location of lesions, the viability of parasites, and the severity of the host immune response. Most patients with parenchymal brain NCC present with few lesions and a relatively benign clinical course, but massive forms of parenchymal NCC can carry a poor prognosis if not well recognized and inappropriately managed. We present the main presentations of massive parenchymal NCC and their differential characteristics. [ABSTRACT FROM AUTHOR]

Background: The pork tapeworm (Taenia solium) is a parasitic helminth that imposes a major health and economic burden on poor rural populations around the world. As recognized by the World Health Organization, a key barrier for achieving control of T. solium is the lack of an accurate and validated simulation model with which to study transmission and evaluate available control and elimination strategies. CystiAgent is a spatially-explicit agent based model for T. solium that is unique among T. solium models in its ability to represent key spatial and environmental features of transmission and simulate spatially targeted interventions, such as ring strategy. Methods/Principal findings: We validated CystiAgent against results from the Ring Strategy Trial (RST)–a large cluster-randomized trial conducted in northern Peru that evaluated six unique interventions for T. solium control in 23 villages. For the validation, each intervention strategy was replicated in CystiAgent, and the simulated prevalences of human taeniasis, porcine cysticercosis, and porcine seroincidence were compared against prevalence estimates from the trial. Results showed that CystiAgent produced declines in transmission in response to each of the six intervention strategies, but overestimated the effect of interventions in the majority of villages; simulated prevalences for human taenasis and porcine cysticercosis at the end of the trial were a median of 0.53 and 5.0 percentages points less than prevalence observed at the end of the trial, respectively. Conclusions/Significance: The validation of CystiAgent represented an important step towards developing an accurate and reliable T. solium transmission model that can be deployed to fill critical gaps in our understanding of T. solium transmission and control. To improve model accuracy, future versions would benefit from improved data on pig immunity and resistance, field effectiveness of anti-helminthic treatment, and factors driving spatial clustering of T. solium infections including dispersion and contact with T. solium eggs in the environment. Author summary: Neurocysticercosis, caused by the ingestion of Taenia solium eggs, is a major cause of human epilepsy around the world. A wide spectrum of tools to fight T. solium is are now available and include antiparasitic treatment for pigs and humans, porcine vaccines, and sanitation improvements; however, the ideal combination of interventions applied to populations to maximize effectiveness and feasibility is not known. Transmission models are one tool that can be used to compare and evaluate different intervention strategies, but no currently available T. solium models have been tested for accuracy. In this research, we validated our model ("CystiAgent") by comparing simulations of the model to the results of a large-scale trial testing a variety of T. solium control interventions. The model was calibrated using observed epidemiological data from these villages and evaluated for its ability to reproduce the effect of T. solium control interventions. The validation showed that the model was able to reproduce the baseline levels of disease, but generally overestimated the effect that each intervention would have on transmission. These results will allow us to identify limitations of the current model to improve future versions, and represent a step forward in the creation of a tool to design and evaluate future programs to control and eliminate T. solium. [ABSTRACT FROM AUTHOR]

Background: Taenia solium (T. solium), is a zoonotic helminth causing three diseases namely; taeniasis (in humans), neurocysticercosis (NCC, in humans) and porcine cysticercosis (PCC, in pigs) and is one of the major foodborne diseases by burden. The success or failure of control options against this parasite in terms of reduced prevalence or incidence of the diseases may be attributed to the contextual factors which underpin the design, implementation, and evaluation of control programmes. Methodology/Principal findings: The study used a mixed method approach combining systematic literature review (SLR) and key informant interviews (KII). The SLR focused on studies which implemented T. solium control programmes and was used to identify the contextual factors and enabling environment relevant to successful inception, planning and implementation of the interventions. The SLR used a protocol pre-registered at the International prospective register of systematic reviews (PROSPERO) number CRD42019138107 and followed PRISMA guidelines on reporting of SLR. To further highlight the importance and interlinkage of these contextual factors, KII were conducted with researchers/implementers of the studies included in the SLR. The SLR identified 41 publications that had considerations of the contextual factors. They were grouped into efficacy (10), effectiveness (28) and scale up or implementation (3) research studies. The identified contextual factors included epidemiological, socioeconomic, cultural, geographical and environmental, service and organizational, historical and financial factors. The enabling environment was mainly defined by policy and strategies supporting T. solium control. Conclusion/Significance: Failure to consider the contextual factors operating in target study sites was shown to later present challenges in project implementation and evaluation that negatively affected expected outcomes. This study highlights the importance of fully considering the various domains of the context and integrating these explicitly into the plan for implementation and evaluation of control programmes. Explicit reporting of these aspects in the resultant publication is also important to guide future work. The contextual factors highlighted in this study may be useful to guide future research and scale up of disease control programmes and demonstrates the importance of close multi-sectoral collaboration in a One Health approach. Author summary: Taenia solium, commonly known as the pork tapeworm is a parasite that, as the etiological agent of neurocysticercosis (the presence of the intermediate state/cysts of the parasite in the central nervous system of humans) is one of the leading causes of acquired epilepsy across endemic areas of sub-Saharan Africa, Southern America and south-east Asia. A variety of biologically efficacious control options exist which include; deworming, provision of clean water and sanitation and appropriate hygiene and food safety education in humans and the vaccination, deworming, confinement and proper feeding of pigs. Despite these, the parasite has not been eliminated and varying impact of interventions has been achieved in the many endemic areas. Failure of the interventions to achieve expected impact could be attributed either to inadequate consideration of various contextual factors, or inability to create an enabling environment needed to underpin success. Contextual factors in this instance are features of the circumstances for which an intervention is conceived and developed and in which it is implemented and evaluated. We conducted a systematic literature review coupled with key informant interviews to identify these contextual factors and show how they may have influenced the implementation and evaluation of control programmes. The study identified that choice of baseline and end line measures, local knowledge, attitude and perceptions of the target population, existing infrastructural and staff capacities, stakeholder participation and support by the national governments through policies and strategies may affect the implementation and evaluation of control interventions. During project inception, there is need to document and understand these contextual factors in order to anticipate the challenges and adapt accordingly. [ABSTRACT FROM AUTHOR]

Background: The parasite Taenia solium causes neurocysticercosis (NCC) in humans and is a common cause of adult-onset epilepsy in the developing world. Hippocampal atrophy, which occurs far from the cyst, is an emerging new complication of NCC. Evaluation of molecular pathways in brain regions close to and distant from the cyst could offer insight into this pathology. Methods: Rats were inoculated intracranially with T. solium oncospheres. After 4 months, RNA was extracted from brain tissue samples in rats with NCC and uninfected controls, and cDNA was generated. Expression of 38 genes related to different molecular pathways involved in the inflammatory response and healing was assessed by RT-PCR array. Results: Inflammatory cytokines IFN-γ, TNF-α, and IL-1, together with TGF-β and ARG-1, were overexpressed in tissue close to the parasite compared to non-infected tissue. Genes for IL-1A, CSF-1, FN-1, COL-3A1, and MMP-2 were overexpressed in contralateral tissue compared to non-infected tissue. Conclusions: The viable cysticerci in the rat model for NCC is characterized by increased expression of genes associated with a proinflammatory response and fibrosis-related proteins, which may mediate the chronic state of infection. These pathways appear to influence regions far from the cyst, which may explain the emerging association between NCC and hippocampal atrophy. Author summary: Taenia solium is a parasite that can infect human brain causing neurocysticercosis. Neurocysticercosis is a common cause of adult-onset epilepsy in the developing world. This infection elicits several cellular and molecular changes as a result of inflammation or parasite-host interaction, which can cause clinical symptoms, such as seizures. Most of these changes have been found in the tissue surrounding to the cysticercus, however, some pathologies, like hippocampal atrophy, which occurs in parts of the brain far from the cyst, are emerging as new complication in NCC patients. Using a rat model, the authors assessed the expression of genes related to different molecular pathways involved in the inflammatory response and healing by the RT-PCR array technique. They found increased expression of genes associated with inflammation and scar tissue formation in tissue surrounding the cyst, as well as tissue far from the cyst, when compared to non-infected brain tissue. This study provides new insights into the inflammatory changes that occur in brain tissue far from viable cysts and may provide evidence for the emerging association between NCC and hippocampal atrophy. [ABSTRACT FROM AUTHOR]

Single brain enhancing lesions (SEL) are the most common presentation of neurocysticercosis (NCC) observed on neuroimaging in people presenting with epileptic seizures not only on the Indian sub-continent and in travelers returning from cysticercosis-endemic regions, but also globally. The aim of this study, which consisted of a systematic review (CRD42019087665), a meta-analysis and an expert group consultation, was to reach consensus on the best anti-seizure medication and anti-inflammatory treatment for individuals with SEL NCC. Standard literature review methods were used, including the Cochrane risk of bias random effects model, meta-analyses were performed and the quality of the body of evidence was rated using GRADE tables. The expert committee included 12 gender and geographically balanced members and recommendations were reached by applying the GRADE framework for guideline development. The 1–1.5-year cumulative incidence of seizure recurrence, cyst resolution or calcification following anti-seizure medication (ASM) withdrawal was not statistically different between ASM of 6, 12 or 24 months. In contrast, in persons whose cyst calcified post treatment, longer ASM decreased seizure recurrence. The cumulative incidence ratio (CIR) 1–1.5 years after stopping ASM was 1.79 95% CI: (1.00, 3.20) for patients given 6 versus 24 months treatment. Duration of treatment had no effect on seizure recurrence in patients whose cyst did not calcify. Anti-inflammatory treatment with corticosteroids in patients treated with ASM compared to patients treated with ASM only showed a statistically significant beneficial effect on seizure reduction (CIR 0.44, 95% CI 0.23, 0.85) and cyst resolution (CIR 1.37, 95%CI: 1.07, 1.75). Our results indicate that ASM in patients with SEL NCC whose cysts resolved can be withdrawn, while patients whose cysts calcified seem to benefit from prolonged anti-seizure medication. Additional corticosteroid treatment was found to have a beneficial effect both on seizure reduction and cyst resolution. Author summary: Neurocysticercosis is an infection of the brain with the tapeworm Taenia solium. On the Indian sub-continent, the majority of people suffering from neurocysticercosis only show one cyst (larval form of the parasite) in their brain and often present at clinics with epileptic seizures. There is still some debate on the best way to treat these cases to reduce the risk for seizure recurrence. The goal of this study was to review the literature on how well different durations of treatment with anti-seizure medication (ASM), combined or not with corticosteroids, work in order to reduce the seizure recurrence and eliminate the cyst from the brain. The results show that ASMfor 24 months compared to 6 months favors reduced seizure recurrence in patients whose cysts calcified post treatment. Concerning anti-inflammatory treatment, corticosteroids were also found to have beneficial effects on seizure reduction. However, further high-quality randomized controlled trials with adequately long follow-up time are required for better evidence on best drug(s), dose and duration of ASM and corticosteroids for individuals with SEL NCC. [ABSTRACT FROM AUTHOR]

Background: The multi-host taeniosis/cysticercosis disease system is associated with significant neurological morbidity, as well as economic burden, globally. We investigated whether lower cost behavioral interventions are sufficient for local elimination of human cysticercosis in Boulkiemdé, Sanguié, and Nayala provinces of Burkina Faso. Methodology/Principal findings: Province-specific data on human behaviors (i.e., latrine use and pork consumption) and serological prevalence of human and pig disease were used to inform a deterministic, compartmental model of the taeniosis/cysticercosis disease system. Parameters estimated via Bayesian melding provided posterior distributions for comparing transmission rates associated with human ingestion of Taenia solium cysticerci due to undercooking and human exposure to T. solium eggs in the environment. Reductions in transmission via these pathways were modeled to determine required effectiveness of a market-focused cooking behavior intervention and a community-led sanitation and hygiene program, independently and in combination, for eliminating human cysticercosis as a public health problem (<1 case per 1000 population). Transmission of cysticerci due to consumption of undercooked pork was found to vary significantly across transmission settings. In Sanguié, the rate of transmission due to undercooking was 6% higher than that in Boulkiemdé (95% CI: 1.03, 1.09; p-value < 0.001) and 35% lower than that in Nayala (95% CI: 0.64, 0.66; p-value < 0.001). We found that 67% and 62% reductions in undercooking of pork consumed in markets were associated with elimination of cysticercosis in Nayala and Sanguié, respectively. Elimination of active cysticercosis in Boulkiemdé required a 73% reduction. Less aggressive reductions of 25% to 30% in human exposure to Taenia solium eggs through sanitation and hygiene programs were associated with elimination in the provinces. Conclusions/Significance: Despite heterogeneity in effectiveness due to local transmission dynamics and behaviors, education on the importance of proper cooking, in combination with community-led sanitation and hygiene efforts, has implications for reducing morbidity due to cysticercosis and neurocysticercosis. Author summary: It is important to consider context-specific behaviors and transmission pathways when designing scalable and sustainable intervention strategies for neglected tropical diseases (NTDs). To reduce the morbidity and mortality associated with cysticercosis, suites of interventions have been recommended but are inconsistently implemented due to cost and feasibility-related constraints. This study investigated the potential of a cooking intervention to interrupt transmission via undercooked pork in marketplaces of Burkina Faso. The sensitivity of Taenia solium parasite to temperatures attainable via improved cooking strategies provides a low-cost, human-centered approach to prevent consumption of infected pork meals. By accounting for different behavior and the relative role of this transmission route across three provinces, we show how the potential of cysticercosis elimination (as a public health problem) varies across behavior-focused interventions. Further investigation into intervention strategies against human and pig cysticercosis warrants data-driven analyses that account for local variation in transmission behaviors. [ABSTRACT FROM AUTHOR]

Racemose neurocysticercosis is an aggressive disease caused by the aberrant expansion of the cyst form of Taenia solium within the subarachnoid spaces of the human brain and spinal cord resulting in a mass effect and chronic inflammation. Although expansion is likely caused by the proliferation and growth of the parasite bladder wall, there is little direct evidence of the mechanisms that underlie these processes. Since the development and growth of cysts in related cestodes involves totipotential germinative cells, we hypothesized that the expansive growth of the racemose larvae is organized and maintained by germinative cells. Here, we identified proliferative cells expressing the serine/threonine-protein kinase plk1 by in situ hybridization. Proliferative cells were present within the bladder wall of racemose form and absent from the homologous tissue surrounding the vesicular form. Cyst proliferation in the related model species Taenia crassiceps (ORF strain) occurs normally by budding from the cyst bladder wall and proliferative cells were concentrated within the growth buds. Cells isolated from bladder wall of racemose larvae were established in primary cell culture and insulin stimulated their proliferation in a dose-dependent manner. These findings indicate that the growth of racemose larvae is likely due to abnormal cell proliferation. The different distribution of proliferative cells in the racemose larvae and their sensitivity to insulin may reflect significant changes at the cellular and molecular levels involved in their tumor-like growth. Parasite cell cultures offer a powerful tool to characterize the nature and formation of the racemose form, understand the developmental biology of T. solium, and to identify new effective drugs for treatment. Author summary: Racemose neurocysticercosis is the most aggressive and lethal form of the disease characterized by progressive expansion of the larval stage of Taenia solium within the subarachnoid spaces of the brain. Currently, the cellular or molecular events that promote its formation and development are unknown. Our observations, employing tissue samples, revealed the presence of mitotically active cells in the bladder wall of the racemose larvae. Finally, we isolated and established primary cell cultures and observed that these cells are sensitive (proliferate in response to insulin). These results suggest that the proliferative cells stimulated by host biomolecules like hormones would be responsible for the abnormal growth of racemose larvae. Further studies are needed to identify all genes and pathways altered in the racemose form. The primary cell cultures will be used as a therapeutic target and allow us in future works to understand the developmental biology of the parasite. [ABSTRACT FROM AUTHOR]

One health (OH) approaches have increasingly been used in the last decade in the fight against zoonotic neglected tropical diseases (NTDs). However, descriptions of such collaborations between the human, animal and environmental health sectors are still limited for French-speaking tropical countries. The objective of the current survey was to explore the diversity of OH experiences applied to research, surveillance and control of NTDs by scientists from French-speaking countries, and discuss their constraints and benefits. Six zoonotic NTDs were targeted: echinococcoses, trypanosomiases, leishmaniases, rabies, Taenia solium cysticercosis and leptospiroses. Invitations to fill in an online questionnaire were sent to members of francophone networks on NTDs and other tropical diseases. Results from the questionnaire were discussed during an international workshop in October 2019. The vast majority (98%) of the 171 respondents considered OH approaches relevant although only 64% had implemented them. Among respondents with OH experience, 58% had encountered difficulties mainly related to a lack of knowledge, interest and support for OH approaches by funding agencies, policy-makers, communities and researchers. Silos between disciplines and health sectors were still strong at both scientific and operational levels. Benefits were reported by 94% of respondents with OH experience, including increased intellectual stimulation, stronger collaborations, higher impact and cost-efficiency of interventions. Recommendations for OH uptake included advocacy, capacity-building, dedicated funding, and higher communities' involvement. Improved research coordination by NTD networks, production of combined human-animal health NTD impact indicators, and transversal research projects on diagnostic and reservoirs were also considered essential. Author summary: The fight against zoonotic diseases, including NTDs, has greatly benefited from One Health approaches over the last 20 years. The results of this survey show the large attraction these approaches have for scientists working on NTD research, surveillance and control activities in French-speaking tropical countries. However, implementing them is still challenging due to inconsistent political will, insufficient dedicated funding and difficulties in building bridges across multiple sectors and disciplines that each have their own vocabulary, priorities, and ways of conducting research and development projects. There is a significant margin of improvement for One Health uptake, which will be favored by studies on prevalence and economic data integrating impacts at the human, animal and environmental levels, and by studies demonstrating the added value of One Health approaches when they are relevant. Scientific NTD networks have a great role to play in terms of breaking down barriers among sectors and disciplines, promoting exchanges of experiences, and coordinating research to avoid duplication and reinforce synergies. In a world where the poorest populations are also the most heavily affected by climatic disasters, social or political crises, and armed conflicts, NTD scientists from all backgrounds need to better team up to develop and implement more effective and impactful research and interventions. [ABSTRACT FROM AUTHOR]

The flatworm Taenia solium causes human and pig cysticercosis. When cysticerci are established in the human central nervous system, they cause neurocysticercosis, a potentially fatal disease. Neurocysticercosis is a persisting public health problem in rural regions of Mexico and other developing countries of Latin America, Asia, and Africa, where the infection is endemic. The great variability observed in the phenotypic and genotypic traits of cysticerci result in a great heterogeneity in the patterns of molecules secreted by them within their host. This work is aimed to identify and characterize cysticercal secretion proteins of T. solium cysticerci obtained from 5 naturally infected pigs from Guerrero, Mexico, using 2D-PAGE proteomic analysis. The isoelectric point (IP) and molecular weight (MW) of the spots were identified using the software ImageMaster 2D Platinum v.7.0. Since most secreted proteins are impossible to identify by mass spectrometry (MS) due to their low concentration in the sample, a novel strategy to predict their sequence was applied. In total, 108 conserved and 186 differential proteins were identified in five cultured cysts. Interestingly, we predicted the sequence of 14 proteins that were common in four out of five cysticercus cultures, which could be used to design vaccines or diagnostic methods for neurocysticercosis. A functional characterization of all sequences was performed using the algorithms SecretomeP, SignalP, and BlastKOALA. We found a possible link between signal transduction pathways in parasite cells and human cancer due to deregulation in signal transduction pathways. Bioinformatics analysis also demonstrated that the parasite release proteins by an exosome-like mechanism, which could be of biological interest. Author summary: Human neurocysticercosis is a major neglected tropical disease caused by Taenia solium. As part of their natural metabolism, cysticerci release molecules into their microenvironment within the host. Secreted molecules could be useful in the design of vaccine candidates or diagnostic methods, or as therapeutic targets. Unfortunately, most secreted proteins cannot be identified by mass spectrometry sequencing due to their low concentration in the sample. In this study, we introduce a novel strategy to predict the sequence of T. solium secreted proteins using 2D-PAGE proteomic analysis and the T. solium genome. This approach allowed us to identify proteins with potential applications in the diagnosis and/or prevention of neurocysticercosis. [ABSTRACT FROM AUTHOR]

Larvae of the cestodes Taenia solium and Taenia crassiceps infect the central nervous system of humans. Taenia solium larvae in the brain cause neurocysticercosis, the leading cause of adult-acquired epilepsy worldwide. Relatively little is understood about how cestode-derived products modulate host neural and immune signalling. Acetylcholinesterases, a class of enzyme that breaks down acetylcholine, are produced by a host of parasitic worms to aid their survival in the host. Acetylcholine is an important signalling molecule in both the human nervous and immune systems, with powerful modulatory effects on the excitability of cortical networks. Therefore, it is important to establish whether cestode derived acetylcholinesterases may alter host neuronal cholinergic signalling. Here we make use of multiple techniques to profile acetylcholinesterase activity in different extracts of both Taenia crassiceps and Taenia solium larvae. We find that the larvae of both species contain substantial acetylcholinesterase activity. However, acetylcholinesterase activity is lower in Taenia solium as compared to Taenia crassiceps larvae. Further, whilst we observed acetylcholinesterase activity in all fractions of Taenia crassiceps larvae, including on the membrane surface and in the excreted/secreted extracts, we could not identify acetylcholinesterases on the membrane surface or in the excreted/secreted extracts of Taenia solium larvae. Bioinformatic analysis revealed conservation of the functional protein domains in the Taenia solium acetylcholinesterases, when compared to the homologous human sequence. Finally, using whole-cell patch clamp recordings in rat hippocampal brain slice cultures, we demonstrate that Taenia larval derived acetylcholinesterases can break down acetylcholine at a concentration which induces changes in neuronal signalling. Together, these findings highlight the possibility that Taenia larval acetylcholinesterases can interfere with cholinergic signalling in the host, potentially contributing to pathogenesis in neurocysticercosis. Author summary: Infection of the human nervous system with larvae of the parasite Taenia solium is a significant cause of acquired epilepsy worldwide. Despite this, the precise cellular and molecular mechanisms underlying epileptogenesis in neurocysticercosis remain unclear. Acetylcholinesterases are a family of enzymes widely produced by helminthic parasites. These enzymes facilitate the breakdown of acetylcholine, which is also a major neurotransmitter in the human nervous system. If T. solium larvae produce acetylcholinesterases, this could potentially disrupt host cholinergic signalling, which may in turn contribute to seizures and epilepsy. We therefore set out to investigate the presence and activity of acetylcholinesterases in T. solium larvae, as well as in Taenia crassiceps larvae, a species commonly used as a model parasite in neurocysticercosis research. We found that both T. crassiceps and T. solium larvae produce acetylcholinesterases with substantial activity and that the functional protein domains in the Taenia solium acetylcholinesterases have great similarity to those of human acetylcholinesterases. We further demonstrate that the acetylcholinesterase activity in the products of these parasites is sufficient to break down acetylcholine at a concentration which induces changes in neuronal signalling in an ex vivo brain slice model. This study provides evidence that Taenia larvae produce acetylcholinesterases and that these can potentially interfere with cholinergic signalling in the host and contribute to pathogenesis in neurocysticercosis. [ABSTRACT FROM AUTHOR]

The neglected zoonotic cestode Taenia solium is endemic in many low- and middle-income countries, including Zambia. The parasite infects humans and pigs, inflicting high socioeconomic and disease burdens in endemic areas. Health education is regarded as an important component in T. solium control and previous studies indicate that 'The Vicious Worm' may be an effective T. solium health education tool for Tanzanian medical and agricultural professionals and Zambian primary school students. This study aimed to assess the effects of health education using 'The Vicious Worm' among Zambian pork supply chain workers, because the pork supply chain greatly influences food safety and security in Zambia. Half-day educational workshops using 'The Vicious Worm' and subsequent follow-up sessions were organized in the Lusaka and Katete districts of Zambia in March and April 2019. Questionnaires were administered before, after, and three weeks after the use of 'The Vicious Worm' to assess the program's impact on knowledge uptake and short-term retention. Focus group discussions were conducted to assess the program's user experience and the participants' beliefs, attitudes, and insights. In total, 47 pork supply chain workers participated: 25 from Lusaka and 22 from Katete. Overall, knowledge about T. solium was significantly higher (p<0.001) both immediately after, and three weeks after the use of 'The Vicious Worm' compared to baseline knowledge. Focus group discussions indicated incipient attitudinal and behavioral change, as well as a positive reception of the software; with participants describing the software as simple, educative, and useful to share knowledge. The study results indicate that workshops using 'The Vicious Worm' may be effective for short-term T. solium health education among key pork supply chain workers. Follow-up studies are required to assess long-term effects, transfer of knowledge and behavioral change. However, educational interventions with 'The Vicious Worm' could be considered for integrated T. solium control programs in sub-Saharan Africa, especially if the educational content is further simplified and clarified. Author summary: The tapeworm Taenia solium causes epilepsy and severe headaches in humans and economic losses to smallholder farmers in endemic areas where free-roaming pigs, poor sanitation and informal animal slaughter are prevalent. Treatment of human taeniosis and interventions in pigs (vaccination and anthelmintic treatment) have been established as essential tools to achieve short-term control, but health education will be crucial to sustain long-term control. 'The Vicious Worm' is a specific T. solium health education tool aiming to convey simple and meaningful messages concerning disease prevention and control. Previous studies found significant knowledge increases after the use of the educational tool in Tanzanian medical and agricultural professionals, and Zambian primary school students. We organized half-day educational workshops using 'The Vicious Worm' for pork supply chain workers at two study sites in Zambia, with follow-up visits three weeks later. We found a significant increase in participants' knowledge, both immediately and three weeks after the health education. Furthermore, the program was well received and potentially led to attitudinal and behavioral change that could deter the propagation of T. solium. We conclude that 'The Vicious Worm' educational interventions may contribute to a safer pork supply chain and we encourage its implementation in future T. solium control strategies. [ABSTRACT FROM AUTHOR]

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. Author summary: The pork tapeworm T. solium affects the health and income of poor people in endemic areas. A pig vaccine—TSOL18, and a drug—oxfendazole (OFZ) present options for its control. In this study we assessed the effectiveness of the two tools against the parasite in pigs. We provided one group of pigs (T1) with a concurrent administration of TSOL18 and OFZ, and another group (T2) with OFZ only, in three rounds at 4 months intervals. We compared infection prevalence before and after the interventions by detection of cysticerci through carcase dissections. In addition, untreated pigs from the T1 and T2 areas were also sacrificed to serve as controls. We found a significant reduction in prevalence within the groups after the interventions. However, the reductions were not significant when compared with the reductions in the control groups, hence could not be definitively attributed to the interventions. Further, concurrent administration of TSOL18 and OFZ cleared infection among assessed pigs whereas OFZ alone did not clear the infection. Further studies would be required to make more definitive conclusions. We advocate for a One Health approach for a more rapid and sustainable impact. [ABSTRACT FROM AUTHOR]

Taenia solium is endemic in Madagascar and presents a significant burden on the population and the health system. The parasite cycles through humans who host the adult tapeworm, and pigs that host the larval stages. Accidental infection of humans may occur with the larval stages which encyst in the nervous central system causing neurocysticercosis, a major cause of seizure disorders and a public health problem. One of the interventions to facilitate the control of the disease is mass drug administration (MDA) of the human population with taeniacide. Here we describe a pilot project conducted in Antanifotsy district of Madagascar from 2015 to 2017 where three annual rounds of MDA (praziquantel, 10mg/Kg) were undertaken in 52 villages. Changes in the prevalence of taeniasis were assessed before, during and after the treatments. A total of 221,308 treatments were given to all eligible people above 5 years of age representing a 95% coverage of the targeted population. No major adverse effects were notified related to the implementation of the MDA. The prevalence of taeniasis was measured using Kato-Katz and copro-antigen techniques. Analyses undertaken combining the results of the Kato-Katz with copro-antigen, or using the Kato-Katz results alone, showed that there was a significant reduction in taeniasis 4 months after the last MDA, but 12 months later (16 months after the last MDA) the taeniasis prevalence had returned to its original levels. Results of the pilot project emphasize the need of a multi-sectorial One-Health approach for the sustained control of T. solium. Author summary: The parasite Taenia solium causes neurocysticercosis in humans in its larval stage and is the main cause of seizure disorders in poor communities that keep pigs (the intermediate host). Diagnosis and treatment of neurocysticercosis remains beyond the reach of the general population in Madagascar. Prevention is therefore the most suitable strategy for combating this disease. Mass drug administration (MDA) is used to treat communities for several parasitic diseases such as schistosomiasis. Infection with the T. solium tapeworm in people can be treated with MDA using praziquantel. Here, we conducted a pilot project in Madagascar, giving over 220,000 treatments to people in 52 villages once per year, for 3 consecutive years. The effects on taeniasis seemed to be encouraging when assessed 4 months after finishing the treatment, but 16 months later, the parasite's prevalence had returned to its original level. MDA was effective in providing temporary control of taeniasis, but parasite transmission was not interrupted. With respect to T. solium, this highlights the need of incorporating other interventions such as vaccination and medication in pigs, improved pig husbandry and meat inspection to tackle the whole cycle of the parasite. [ABSTRACT FROM AUTHOR]

Background: Estimating the burden of neglected tropical diseases is a valuable tool to support policymakers in the resource allocation for control and elimination of these diseases. Spatial analysis allows to identify the geographical distribution patterns of infectious and parasitic diseases within a country and allows to assess their possible correlation with other health disorders. Despite being neurocysticercosis (NCC) considered as the most important parasitic disease of the nervous system, few efforts have been addressed to assess the real burden of NCC in endemic countries, to date, there are no studies estimating the burden of NCC in South America. In this study we aimed to use the Disability Adjust Life Years (DALY) and spatial indicators as tools to measure the impact of human neurocysticercosis in Ecuador between 2013 and 2017. Methods: Mortality, morbidity and spatial data from the national agency of statistics were used to estimate the burden of disease of NCC during a five-year period (2013–2017). NCC cases and its two main sequelae, epilepsy and migraine headache, were stratified by sex and age group to calculate the DALY associated to NCC using the DALY package in R. SATSCAN software was used to assess spatial clusters of NCC and its possible neurological sequelae as epilepsy, status epilepticus, migraine and hydrocephalus. Principal findings: The burden of human neurocysticercosis ranged from 56201 [95% CI 29961–89333] to 59612 [95% CI 31854–94689] DALY per year, corresponding to 3.54 to 3.56 DALY per 1000 population. Average yearly incidence rates per 10 000 person-years were 0.23 [95% CI 0.21–0.26] for NCC, 4.89 [95% CI 4.78–5.00] for epilepsy, 0.130 [95% CI 0.11–0.15] for status epilepticus, 0.62 [95% CI 0.58–0.66] for migraine headache, and 1.02 [95% CI 0.98–1.07] for hydrocephalus. Most important significant spatial clusters (p<0.0001) were located in the southern region of the highlands of the country. Conclusion/Significance: This is the first study in South America to calculate estimates for burden of NCC and one of the few using spatial analysis to show the importance of sequelae other than epilepsy that play an important role in the impact of human neurocysticercosis. Author summary: Taenia solium-neurocysticercosis (NCC) is a neglected parasite infection in humans causing a variety of neurological sequelae like epilepsy, and chronic headache. The purpose of this study was to estimate the burden of NCC in Ecuador using official nation-wide databases from the National Institute of Statistics and Census (INEC) for the period of 2013–2017, and to assess for spatial clusters of four neurological disorders associated with NCC. The burden of NCC measured in Disability Adjusted Life Years (DALY) was estimated in 3.54 to 3.56 DALY per 1000 population. Several significant spatial clusters for augmented risk of disease were identified along the country for NCC and its sequelae, most of which converged in the southern Sierra provinces. Our study suggests a possible spatial correlation between the presence of NCC cases and a higher prevalence of neurological conditions like epilepsy, status epilepticus, migraine, and hydrocephalus in several 'hot spots' of the southern provinces of Ecuador, indicating possible areas where the application of preventive measures is necessary to reduce cysticercosis transmission rates. [ABSTRACT FROM AUTHOR]

Taenia solium cysticercosis and taeniasis (TSCT), caused by the tapeworm T. solium, is a foodborne and zoonotic disease classified since 2010 by WHO as a neglected tropical isease. It causes considerable impact on health and economy and is one of the leading causes of acquired epilepsy in most endemic countries of Latin America, Sub-Saharan Africa, and Asia. There is some evidence that the prevalence of TSCT in high-income countries has recently increased, mainly due to immigration from endemic areas. In regions endemic for TSCT, human cysticercosis can manifest clinically as neurocysticercosis (NCC), resulting in epileptic seizures and severe progressive headaches, amongst other neurological signs and/or symptoms. The development of these symptoms results from a complex interplay between anatomical cyst localization, environmental factors, parasite's infective potential, host genetics, and, especially, host immune responses. Treatment of individuals with active NCC (presence of viable cerebral cysts) with anthelmintic drugs together with steroids is usually effective and, in the majority, reduces the number and/or size of cerebral lesions as well as the neurological symptoms. However, in some cases, treatment may profoundly enhance anthelmintic inflammatory responses with ensuing symptoms, which, otherwise, would have remained silent as long as the cysts are viable. This intriguing silencing process is not yet fully understood but may involve active modulation of host responses by cyst-derived immunomodulatory components released directly into the surrounding brain tissue or by the induction of regulatory networks including regulatory T cells (Treg) or regulatory B cells (Breg). These processes might be disturbed once the cysts undergo treatment-induced apoptosis and necrosis or in a coinfection setting such as HIV. Herein, we review the current literature regarding the immunology and pathogenesis of NCC with a highlight on the mobilization of immune cells during human NCC and their interaction with viable and degenerating cysticerci. Moreover, the immunological parameters associated with NCC in people living with HIV/AIDS and treatments are discussed. Eventually, we propose open questions to understand the role of the immune system and its impact in this intriguing host–parasite crosstalk. [ABSTRACT FROM AUTHOR]

Background: Preventive chemotherapy is a useful tool for the control of Taenia solium taeniasis and cysticercosis. The aim of this systematic review is to assess the scientific evidence concerning the effectiveness and safety of different drugs in preventive chemotherapy for T. solium taeniasis in endemic populations. Methods: A systematic review was conducted of controlled and uncontrolled studies, assessing the efficacy and adverse effects (among other outcomes) of albendazole, niclosamide and/or praziquantel for preventive chemotherapy of T. solium taeniasis. A comprehensive search was conducted for published and unpublished studies. Two reviewers screened articles, completed the data extraction and assessment of risk of bias. A meta-analysis of cure rate and relative reduction in prevalence was performed. The protocol for this review was registered on the International prospective register of systematic reviews (PROSPERO), number CRD42018112533. Results: We identified 3555 records, of which we included 20 primary studies reported across 33 articles. Meta-analyses of drug and dose showed that a single dose of praziquantel 10mg/kg, albendazole 400mg per day for three consecutive days, or niclosamide 2g, resulted in better cure rates for T. solium taeniasis (99.5%, 96.4% and 84.3%, respectively) than praziquantel 5mg/kg or single dose albendazole 400mg (89.0% and 52.0%, respectively). These findings have a low certainty of evidence due to high risk of bias in individual studies and heterogeneity in combined estimates. In relation to side-effects, most studies reported either no or only mild and transient side-effects within the first three days following drug administration for all drugs and doses. Conclusion: Evidence indicated that praziquantel 10mg/kg, niclosamide 2g, and triple dose albendazole 400mg were effective as taenicides and could be considered for use in mass drug administration programs for the control of T. solium taeniasis. Evidence was not found that any of these drugs caused severe side effects at the indicated doses, although the extent of the available evidence was limited. Author summary: Taeniasis and cysticercosis caused by Taenia solium are considered, by the WHO, to be neglected tropical diseases. Preventive chemotherapy for taeniasis in endemic populations is a useful tool for control of the parasite. Preventive chemotherapy can be implemented by treating the whole population in endemic areas at regular intervals (known as mass drug administration). While different drugs, doses and regimes have been used there were still uncertainties about which drugs and dose have the best efficacy while considering adverse effects. We conducted a systematic review of the best available literature to inform a WHO guideline for preventive chemotherapy. We found that praziquantel 10mg/kg, niclosamide 2g, and triple dose albendazole 400mg (400mg per day for three consecutive days) are all effective. Proven side-effects were mild and short-lived, when they did occur. [ABSTRACT FROM AUTHOR]

Triosephosphate isomerases (TPIs) from Taenia solium (TsTPI) and Schistosoma mansoni (SmTPI) are potential vaccine and drug targets against cysticercosis and schistosomiasis, respectively. This is due to the dependence of parasitic helminths on glycolysis and because those proteins elicit an immune response, presumably due to their surface localization. Here we report the crystal structures of TsTPI and SmTPI in complex with 2-phosphoglyceric acid (2-PGA). Both TPIs fold into a dimeric (β-α)8 barrel in which the dimer interface consists of α-helices 2, 3, and 4, and swapping of loop 3. TPIs from parasitic helminths harbor a region of three amino acids knows as the SXD/E insert (S155 to E157 and S157 to D159 in TsTPI and SmTPI, respectively). This insert is located between α5 and β6 and is proposed to be the main TPI epitope. This region is part of a solvent-exposed 310–helix that folds into a hook-like structure. The crystal structures of TsTPI and SmTPI predicted conformational epitopes that could be used for vaccine design. Surprisingly, the epitopes corresponding to the SXD/E inserts are not the ones with the greatest immunological potential. SmTPI, but not TsTPI, habors a sole solvent exposed cysteine (SmTPI-S230) and alterations in this residue decrease catalysis. The latter suggests that thiol-conjugating agents could be used to target SmTPI. In sum, the crystal structures of SmTPI and TsTPI are a blueprint for targeted schistosomiasis and cysticercosis drug and vaccine development. Author summary: Because of the worldwide prevalence of schistosomiasis and cysticercosis, it is critical to develop drugs and vaccines against their causative agents. The glycolytic enzyme triosephosphate isomerase (TPI) is a dual-edged sword against diseases caused by parasitic helminths. This is because helminths heavily depend on glycolysis for energy and because the surface localization exhibited by TPIs that elicits an immune response against those organisms. Here we provide the crystal structures TPIs from Taenia solium and Schistosoma mansoni as a first step for vaccine and drug design. As a proof of concept we found that modifications in the single solvent exposed cysteine of TPI from S. mansoni decreases catalysis, making this enzyme a novel target against schistosomiasis. [ABSTRACT FROM AUTHOR]

In Africa, urbanization is happening faster than ever before which results in new implications for transmission of infectious diseases. For the zoonotic parasite Taenia solium, a major cause of acquired epilepsy in endemic countries, the prevalence in urban settings is unknown. The present study investigated epidemiological, neurological, and radiological characteristics of T. solium cysticercosis and taeniasis (TSCT) in people with epilepsy (PWE) living in Dar es Salaam, Tanzania, one of the fastest growing cities worldwide. A total of 302 PWE were recruited from six health centers in the Kinondoni district of Dar es Salaam. Serological testing for T. solium cysticercosis-antigen (Ag) and -antibodies (Abs) and for T. solium taeniasis-Abs was performed in all PWE. In addition, clinical and radiological examinations that included cranial computed tomography (CT) were performed. With questionnaires, demographic data from study populations were collected, and factors associated with TSCT were assessed. Follow-up examinations were conducted in PWE with TSCT. T. solium cysticercosis-Ag was detected in three (0.99%; 95% CI: 0–2.11%), -Abs in eight (2.65%; 95% CI: 0.84–4.46%), and taeniasis-Abs in five (1.66%; 95% CI: 0.22–3.09%) of 302 PWE. Six PWE (1.99%; 95% CI: 0.41–3.56%) were diagnosed with neurocysticercosis (NCC). This study demonstrates the presence of TSCT in Dar es Salaam, however, NCC was only associated with a few cases of epilepsy. The small fraction of PWE with cysticercosis- and taeniasis-Abs may suggest that active transmission of T. solium plays only a minor role in Dar es Salaam. A sufficiently powered risk analysis was hampered by the small number of PWE with TSCT; therefore, further studies are required to determine the exact routes of infection and risk behavior of affected individuals. Author summary: Taenia solium cysticercosis and taeniasis is a zoonotic disease complex which affects thousands of people in sub-Saharan Africa. This parasite has a human-pig life cycle and has been considered a public health problem mainly in rural areas. As African towns and suburbs grow rapidly and disproportionally, adequate infrastructure such as sewage systems and clean water often lack while population density, trade, and travel increase. This may lead to the appearance of parasitic diseases formerly considered 'rural´ in urban settings. In this study, we searched for evidence of T. solium infections in the Kinondoni district of Dar es Salaam, Tanzania. We focused on people with epilepsy (PWE) since epilepsy is one of the most common and severe disorders associated with T. solium neurocysticercosis and tested all of them serologically for T. solium cysticercosis and taeniasis. We further investigated neurological and radiological characteristics. Our findings show that in our study area in Dar es Salaam 2.65% of PWE had contracted T. solium infection at some stage. Neurocysticercosis, as confirmed by neuroimaging, was found only in 1.99% of PWE. This, in combination with the relatively small number of PWE detected with taeniasis antibodies (1.66%), points towards the fact that active transmission of T. solium seems to play only a minor role in this urban setting, suggesting that infections may mainly be contracted in rural areas. Further large-scale studies are required to investigate the infection pathways and risk behavior related to T. solium infections within urban areas of sub-Saharan Africa. [ABSTRACT FROM AUTHOR]

We developed a novel and portable fluorescent sensor that integrates a lateral flow assay with a quantum dot (Qdots) label and a mobile phone reader for detection of specific antibodies in human serum. We evaluated the utility of this assay to test for antibodies to the Taenia solium rT24H antigen. It was a retrospective study by examining 112 positive human sera from patients with neurocysticercosis (NCC) including samples from patients with single viable cyst (n = 18), two or more viable cysts (n = 71), and subarachnoid (racemose) cysts (n = 23). These samples were collected from previous study subjects in Lima, Peru that conducted under an approved study protocol in Peru. The sera were made anonymous under a protocol approved by the CDC Institutional Review Board. Definitive diagnosis of the specimen was established by computed-tomography and/or magnetic resonance imaging. To test the specificity of the assay, we evaluated a panel of serum samples obtained from patients with other infections (n = 24), and serum samples from persons in the United States and Egypt who had not traveled outside their country, and therefore are presumed negative for cysticercosis (n = 128). The assay specificity in the negative panel was 99% (95–100%) while assay sensitivity was 89% (79–95%) in NCC patients with two or more viable cysts. Our assay has performance characteristics similar to those of traditional platforms for the detection of NCC and shows promise as a mobile phone reader-based point-of-care test for antibody detection. [ABSTRACT FROM AUTHOR]

Background: Taenia solium cysticercosis is a public health and agricultural problem in many low and middle-income countries where health education, sanitation, pig management practices and meat inspection infrastructure are insufficient. Cysticercosis affects both human and animal health and has important economic consequences. Very few studies have been conducted to evaluate the monetary burden of cysticercosis. This study aimed at estimating the 2015 costs associated with cysticercosis in humans and pigs in Mexico. Methods: The monetary burden of human cysticercosis was estimated based on costs incurred by living with and treating epilepsy and severe chronic headaches associated with neurocysticercosis (NCC). The estimated cost of porcine cysticercosis took into consideration losses due to the reduction in the price of cysticercosis-infected animals. Epidemiologic and economic data were obtained from the published literature, government reports, and setting-specific questionnaires. Latin hypercube sampling methods were employed to sample the distributions of uncertain parameters and to estimate 95% credible regions (95% CRs). All results are reported in 2015 U.S.$. Findings: The overall monetary burden associated with NCC morbidity was estimated at U.S.$215,775,056 (95% CR U.S.$109,309,560 –U.S.$361,924,224), with U.S.$436 (95% CR: U.S.$296 –U.S.$604) lost per patient. If loss of future years of income and productivity due to NCC-associated deaths was included, this value increased by U.S.$54.26 million, assuming that these individuals earned Mexico’s median wage salary. An additional U.S.$19,507,171 (95% CR U.S.$5,734,782 –U.S.$35,913,487) was estimated to be lost due to porcine cysticercosis. Conclusions: This study suggests that T. solium cysticercosis results in considerable monetary losses to Mexico. [ABSTRACT FROM AUTHOR]

The definitive method for diagnosis of porcine cysticercosis is the detection of cysticerci at necropsy. Cysts are typically located in the striated muscle and brain. Until recently Taenia solium cysticerci have not been definitively identified in other tissue locations, despite several comprehensive investigations having been undertaken which included investigation of body organs other than muscle and brain. Recently a study conducted in Zambia reported 27% infection with T. solium in the liver of pigs with naturally acquired porcine cysticercosis, as well as some T. solium infection in the lungs and spleen of some animals. We investigated the cause of lesions in sites other than the muscle or brain in a total of 157 pigs from T. solium endemic regions of Uganda and Nepal which were subjected to extensive investigations at necropsy. Lesions which had the potential to be caused by T. solium were characterised by macroscopic and microscopic examination, histology as well as DNA characterisation by PCR-RFLP and sequencing. Lesions were confirmed as being caused by Taenia hydatigena (both viable and non-viable), by T. asiatica and Echinococcus granulosus (in Nepal) and nematode infections. No T. solium-related lesions or cysticerci were identified in any tissue other than muscle and brain. It is recommended that future evaluations of porcine cysticercosis in aberrant tissue locations include DNA analyses that take appropriate care to avoid the possibility of contamination of tissue specimens with DNA from a different tissue location or a different animal. The use of appropriate control samples to confirm the absence of cross-sample contamination is also recommended. [ABSTRACT FROM AUTHOR]

Background: Taenia solium is a neglected zoonotic parasite endemic throughout many low-income countries worldwide, including Zambia, where it causes human and pig diseases with high health and socioeconomic burdens. Lack of knowledge is a recognized risk factor, and consequently targeted health educational programs can decrease parasite transmission and disease occurrence in endemic areas. Preliminary assessment of the computer-based education program ‘The Vicious Worm’ in rural areas of eastern Zambia indicated that it was effective at increasing knowledge of T. solium in primary school students. The aim of this study was to evaluate the impact of ‘The Vicious Worm’ on knowledge retention by re-assessing the same primary school students one year after the initial education workshops. Methodology/Principal findings: Follow-up questionnaires were administered in the original three primary schools in eastern Zambia in 2017, 12 months after the original workshops. In total, 86 pupils participated in the follow-up sessions, representing 87% of the initial workshop respondents. Knowledge of T. solium at ‘follow-up’ was significantly higher than at the initial ‘pre’ questionnaire administered during the Vicious Worm workshop that took place one year earlier. While some specifics of the parasite’s life cycle were not completely understood, the key messages for disease prevention, such as the importance of hand washing and properly cooking pork, remained well understood by the students, even one year later. Conclusions/Significance: Results of this study indicate that ‘The Vicious Worm’ may be an effective tool for both short- and long-term T. solium education of rural primary school students in Zambia. Inclusion of educational workshops using ‘The Vicious Worm’ could be recommended for integrated cysticercosis control/elimination programs in sub-Saharan Africa, particularly if the content is simplified to focus on the key messages for prevention of disease transmission. [ABSTRACT FROM AUTHOR]

As members of the Pan American Health Organization (PAHO) and World Health Organization (WHO) guidelines development group on chemotherapy strategies for the control of Taenia solium taeniasis, we are very disappointed at the systematic review by Haby and colleagues. With respect to the analysis of efficacy, the authors did not account for differences in the methods used to ascertain the outcome in the studies analyzed. There are also major concerns regarding the safety analyses. Few of the included studies used carefully designed active surveillance protocols to detect epileptic seizures and/or chronic progressive headaches. These neurologic side effects, due the inadvertent killing of viable brain cysts, have been noted after mass therapy with praziquantel and albendazole. We wholeheartedly agree with the authors' statement in their discussion that control programs applying chemotherapy using mass drug administration "need to be informed by evidence of the best drug and dose in terms of efficacy and side-effects." Unfortunately, the flawed analysis that was published is contrary to that goal. [ABSTRACT FROM AUTHOR]

Taenia solium is known to cause human cysticercosis while T. saginata does not. Comparative in vitro and in vivo studies on the oncosphere and the postoncospheral (PO) forms of T. solium and T. saginata may help to elucidate why cysticercosis can occur from one and not the other. The aim of this study was to use in vitro culture assays and in vivo models to study the differences in the development of the T. solium and T. saginata oncosphere. Furthermore, this study aimed to evaluate the expression of cytokines and metalloproteinases (MMPs) in human peripheral blood mononuclear cells (PBMCs), which were stimulated by these oncospheres and PO antigens. T. solium and T. saginata activated oncospheres (AO) were cultured in INT-407 and HCT-8 intestinal cells for 180 days. The T. solium began to die while the T. saginata grew for 180 days and developed to cysticerci in INT-407 cells. Rats were inoculated intracranially with AO and PO forms of either T. saginata or T. solium. Rats infected with T. solium AO and PO forms developed neurocysticercosis (NCC), while those infected with the T. saginata did not. Human PMBCs were stimulated with antigens of AO and PO forms of both species, and the production of cytokines and metalloproteinases (MMPs) was measured. The T. solium AO antigen stimulated a higher production of IL-4, IL-5, IL-13, IFN-γ, and IL-2 cytokines compared to T. saginata AO. In the PO form, the T. saginata PO antigen increased the production of IL-4, IL-5, IL-13, IFN-γ, IL-1β, IL-6, IL-10, TNF-α and IL-12 cytokines compared to T. solium, suggesting that this global immune response stimulated by different forms could permit survival or destruction of the parasite depending of their life-cycle stage. Regarding MMPs, T. solium AO antigen stimulated a higher production of MMP-9 compared to T. saginata AO antigen, which may be responsible for altering the permeability of intestinal cells and facilitating breakdown of the blood-brain barrier during the process of invasion of host tissue. [ABSTRACT FROM AUTHOR]

Taenia solium is a zoonotic cestode parasite which causes human neurocysticercosis. Pigs transmit the parasite by acting as the intermediate host. An intervention was implemented to control transmission of T. solium by pigs in Dalit communities of Banke District, Nepal. Every 3 months, pigs were vaccinated with the TSOL18 recombinant vaccine (Cysvax, IIL, India)) and, at the same time, given an oral treatment with 30mg/kg oxfendazole (Paranthic 10% MCI, Morocco). The prevalence of porcine cysticercosis was determined in both an intervention area as well as a similar no intervention control area, among randomly selected, slaughter-age pigs. Post mortem assessments were undertaken both at the start and at the end of the intervention. Participants conducting the post mortem assessments were blinded as to the source of the animals being assessed. At the start of the intervention the prevalence of porcine cysticercosis was 23.6% and 34.5% in the control and intervention areas, respectively. Following the intervention, the prevalence of cysticercosis in pigs from the control area was 16.7% (no significant change), whereas no infection was detected after complete slicing of all muscle tissue and brain in animals from the intervention area (P = 0.004). These findings are discussed in relation to the feasibility and sustainability of T. solium control. The 3-monthly vaccination and drug treatment intervention in pigs used here is suggested as an effective and practical method for reducing T. solium transmission by pigs. The results suggest that applying the intervention over a period of years may ultimately reduce the number of tapeworm carriers and thereby the incidence of NCC. [ABSTRACT FROM AUTHOR]

Background: Taenia solium (T. solium) cysticercosis remains a neglected zoonotic disease in India. The current study was planned to estimate the prevalence of T. solium porcine cysticercosis in the Punjab state of India, to compare this prevalence with the disease prevalence in pigs reared outside Punjab and to assess the distribution of the parasite in pig carcasses. Methods: Two slaughter shops were selected in each of the 22 districts of Punjab. Pigs slaughtered on the day/s of inspection were post-mortem inspected to identify the presence of T. solium cysts. Estimated true prevalence was estimated by taking into account the diagnostic sensitivity (38%) and specificity (100%) of post-mortem inspection using the Rogan-Gladen estimator. Positive carcasses were purchased and brought to the laboratory to assess the tissue distribution of T. solium cysts and to conduct PCR targeting large subunit rRNA gene, internal transcribed spacer 1 gene, ITS1 gene and Cytochrome oxidase I gene. The selected PCR products were submitted for sequencing and phylogenetic analyses were performed. Findings: We contacted 71 shop owners to achieve a sample of 44 shops for the study. We inspected 642 pigs reared in Punjab and 450 imported from other states at these slaughter shops. In addition, we sampled 40 pigs from an abattoir located in the state capital. Of the 642 pigs reared in Punjab, 9 had T. solium cysts with an apparent prevalence of 1·40% (95% CI: 0·74%, 2·64%) and the estimated true prevalence of 3.69% (95% CI: 1·95%, 6·95%). Pigs imported from outside the state had a significantly higher prevalence (odds ratio: 2·58; 95% CI: 1·12, 5·98; p-value: 0·026) as 15 of the 450 imported pigs were positive (apparent prevalence: 3.33%; 95% CI: 2.03%, 5.43%; estimated true prevalence: 8.77%; 95% CI: 5.34%, 14.28%). None of samples was positive from the pigs sampled at the abattoir in the state capital. The PCR confirmed T. solium cysts from all the 24 positive samples. We counted a median of 897 (range 526–1964) cysts per infected pig from the 19 infected pig carcasses inspected. The phylogenetic tree based on the alignment of partial cytochrome oxidase 1 sequences indicated all positive samples to be clustered with the T. solium Asian genotype. The analysis did not indicate the presence of T. asiatica in the slaughter pigs. Conclusions: Despite the underestimation of the prevalence due to missing mildly-infected carcasses, low participation and lack of representative sampling, the presence of heavily infected carcasses containing viable cysts, particularly those imported from outside the state, indicates that T. solium cysticercosis is an important food safety concern for pork consumers in Punjab, India. Measures should be taken to reduce the disease prevalence in pigs to reduce the disease burden in the public. [ABSTRACT FROM AUTHOR]

Background: Taenia solium, a pork-borne parasitic zoonosis, is the cause of taeniasis and cysticercosis in humans. In Vietnam, poor sanitation, the practice of outdoor defecation and consumption of raw/undercooked pork have been associated with infection/exposure to T. solium in both humans and pigs. The broad-scale geographic distribution of the prevalence of T. solium varies throughout the country with infection restricted to isolated foci in the north and a more sporadic geographic distribution in the Central Highlands and the south. While cross-sectional studies have allowed the broad-scale geographic distribution of T. solium to be described, details of the geographic distribution of T. solium at finer spatial scales have not been described in detail. This study provides a descriptive spatial analysis of T. solium exposure in humans and pigs and T. solium taeniasis in humans within individual households in village communities of Dak Lak in the Central Highlands of Vietnam. Methodology/Principal findings: We used Ripley’s K-function to describe spatial dependence in T. solium exposure positive and negative human and pig households and T. solium taeniasis exposure positive and negative households in villages within the districts of Buon Don, Krong Nang and M’Drak of Dak Lak province in the Central Highlands of Vietnam. The prevalence of exposure to T. solium in pigs in Dak Lak province was 9 (95% CI 5 to 17) cases per 1000 pigs at risk. The prevalence of exposure to the parasite in humans was somewhat higher at 5 (95% CI 3 to 8) cases per 100 individuals at risk. Spatial aggregations of T. solium exposure-positive pig and human households occurred in some, but not all of the villages in the three study districts. Human exposure-positive households were found to be aggregated within a distance of 200 to 300 m in villages in Krong Nang district compared with distances of up to 1200 m in villages in M’Drak district. Although this study demonstrated the aggregation of households in which either T. solium exposure- or taeniasis-positive individuals were present, we were unable to identify an association between the two due to the very low number of T. solium taeniasis-positive households. Conclusions: Spatial aggregations of T. solium exposure-positive pig and human households occurred in some, but not all of the villages in the three study districts. We were unable to definitively identify reasons for these findings but speculate that they were due to a combination of demographic, anthropological and micro-environmental factors. To more definitively identify characteristics that increase cysticercosis risk we propose that cross-sectional studies similar in design to that described in this paper should be applied in other provinces of Vietnam. [ABSTRACT FROM AUTHOR]

Background: Control and elimination of zoonotic diseases requires robust information about their effect on both human and livestock health in order to enable policy formulation and the allocation of resources. This study aimed to evaluate the cost-effectiveness of controlling Taenia solium taeniasis/cysticercosis in both humans and pigs, and soil-transmitted helminths (STH) in humans by integrating their control to on-going human and animal health control programmes in northern Lao People’s Democratic Republic. Method: A cross-sectional study was carried out in 49 households, focusing on the prevalence of T. solium taenias/cysticercosis and soil transmitted helminths before and after a twelve month intervention. The village data was collected using a semi-structured questionnaire through a door-to-door survey. The village data was then projected to the wider northern Lao PDR population using stochastic modelling and cost-effectiveness ratio (after aggregating the net cost to capture both human and animal health parameters) and GDP per capita as a threshold, to determine the cost-effectiveness of the integrated control of T. solium taeniasis/ cysticercosis and STH, assuming linear scaling out of the intervention. The zoonotic DALY (zDALY) approach was also used as an alternative method of estimating the cost-effectiveness ratio of controlling T. solium taeniasis/cysticercosis in humans and pigs. Findings: Using cost-effectiveness analysis after aggregating the net cost and control of T. solium taeniasis/cysticercosis alone as the base case, the study found that simultaneous control of T. solium taeniasis/cysticercosis in humans and pigs, STH in humans and Classical Swine Fever (CSF) in pigs was USD 14 per DALY averted and USD 234 per zDALY averted using zDALY method hence considered highly cost-effective whereas controlling T. solium taeniasis/cysticercosis without incorporating STH and CSF was the least cost-effective (USD 3,672 per DALY averted). Additionally, the cost-effectiveness of controlling T. solium taeniasis/cysticercosis in people and pigs using zDALY as an alternative method was USD 3,662 per zDALY averted which was quite close to our findings using the aggregate net cost method. Conclusion: The study showed that control of T. solium taeniasis/cysticercosis alone in humans and pigs is not cost-effective in northern Lao PDR whereas control of STH is. Consequently, integrating T. solium taeniasis/cysticercosis control with other cost-effective programmes such as STH and CSF markedly improved the cost-effectiveness of the intervention. This is especially important in low resource countries where control of zoonotic neglected tropical diseases could be integrated with the human and animal health sectors to optimize use of the limited resources. Trial registration: Australia New Zealand Clinical Trials Registry (ANZCTR) . [ABSTRACT FROM AUTHOR]

Background: Cysticercosis (CC) is a tissue infection caused by the larval cysts of the pork tapeworm Taenia solium. It is usually acquired by eating contaminated food or drinking water. CC Cysts can develop in the muscles, the eyes, the brain, and/or the spinal cord. T. solium is found worldwide, but its prevalence has decreased in developed countries due to stricter meat inspection and better hygiene and sanitation. Nevertheless, CC is still a leading cause of seizures and epilepsy. In Spain, The disease is not nationally reportable and data on CC infected animals are also missing, despite the European Directive 2003/99/EC. Methodology/Principal findings: We performed a retrospective descriptive study using the Spanish Hospitalization Minimum Data Set (CMBD). Data with ICD-9 CM cysticercosis code (“123.1”) placed in first or second diagnostic position from 1997 to 2014 were analyzed. Hospitalization rates were calculated and clinical characteristics were described. Spatial distribution of cases and their temporal behavior were also assessed. A total of 1,912 hospital discharges with clinical cysticercosis were identified. From 1998 to 2008, an increasing trend in the number of CC hospitalizations was observed, decreasing afterwards, in parallel with a decrease in the external migration rate. The Murcia region had the highest median hospitalization rate (13.37 hospitalizations/100,000 population), followed by Navarra and Madrid. The 16–44 age group was the most represented (63.6%). The three most frequent associated diagnoses were epilepsy and convulsions (49.5%), hydrocephalus (11.8%) and encephalitis/myelitis/meningitis (11.6%). Conclusions/Significance: There is a need for a common strategy on data collection, monitoring and reporting, which would facilitate a more accurate picture on the CC epidemiological scenario. Even if most cases might be imported, improving the human and animal CC surveillance will result useful both in gaining extended disease knowledge and reducing morbidity and related-costs. [ABSTRACT FROM AUTHOR]

Most part of Southeast Asia is considered endemic for human-infecting Taenia tapeworms; Taenia solium, T. saginata, and T. asiatica. However, until now there was no report of the occurrence of human cases of T. asiatica in Lao PDR. This study, conducted in Savannakhet Province, Lao PDR, microscopically examined a total of 470 fecal samples by Kato Katz method and found 86% of people harboring at least one helminth. Hookworms were detected in 56% of the samples besides Opisthorchis like eggs (42%), Trichuris trichiura (27%), Ascaris spp. (14%), and Taenia spp. (4%) eggs. Serology for cysticercosis showed 6.8% positives with results varying from 3% to 14.3% in Ethnic School students and Kalouk Kao village respectively. Species-specific PCR targeting mitochondrial DNA (mtDNA) of 28 tapeworms, recovered from 16 patients, revealed T. solium (n = 2), T. saginata (n = 21), and T. asiatica (n = 5). Two patients were confirmed to be coinfected with T. saginata and T. asiatica, indicating the endemicity of the 3 human Taenia in Lao PDR. However, nucleotide sequencing of a nuclear DNA gene, DNA polymerase delta (pold) revealed that all the tapeworms identified as T. asiatica using mtDNA had T. saginata type allele at pold locus, demonstrating that they are not “pure T. asiatica” but the hybrid descendants between the two species, confirming the wide distribution of hybrids of T. saginata/ T. asiatica in Southeast Asia. The high prevalence of several helminthic NTDs in east Savannakhet area even with conventional control measures indicates the importance to establish wide and multifaceted health programs to sustainably improve the quality of life of the populations living in these communities. [ABSTRACT FROM AUTHOR]

The adult Taenia solium, the pork tapeworm, usually lives as a single worm in the small intestine of humans, its only known definitive host. Mechanisms of genetic variation in T. solium are poorly understood. Using three microsatellite markers previously reported [], this study explored the genetic variability of T. solium from cysts recovered from experimentally infected pigs. It then explored the genetic epidemiology and transmission in naturally infected pigs and adult tapeworms recovered from human carriers from an endemic rural community in Peru. In an initial study on experimental infection, two groups of three piglets were each infected with proglottids from one of two genetically different tapeworms for each of the microsatellites. After 7 weeks, pigs were slaughtered and necropsy performed. Thirty-six (92.3%) out of 39 cysts originated from one tapeworm, and 27 (100%) out of 27 cysts from the other had exactly the same genotype as the parental tapeworm. This suggests that the microsatellite markers may be a useful tool for studying the transmission of T. solium. In the second study, we analyzed the genetic variation of T. solium in cysts recovered from eight naturally infected pigs, and from adult tapeworms recovered from four human carriers; they showed genetic variability. Four pigs had cysts with only one genotype, and four pigs had cysts with two different genotypes, suggesting that multiple infections of genetically distinct parental tapeworms are possible. Six pigs harbored cysts with a genotype corresponding to one of the identified tapeworms from the human carriers. In the dendrogram, cysts appeared to cluster within the corresponding pigs as well as with the geographical origin, but this association was not statistically significant. We conclude that genotyping of microsatellite size polymorphisms is a potentially important tool to trace the spread of infection and pinpoint sources of infection as pigs spread cysts with a shared parental genotype. [ABSTRACT FROM AUTHOR]

In human and porcine cysticercosis caused by the tapeworm Taenia solium, the larval stage (cysts) can infest several tissues including the central nervous system (CNS) and the skeletal muscles (SM). The cyst’s proteomics changes associated with the tissue localization in the host tissues have been poorly studied. Quantitative multiplexed proteomics has the power to evaluate global proteome changes in response to different conditions. Here, using a TMT-multiplexed strategy we identified and quantified over 4,200 proteins in cysts obtained from the SM and CNS of pigs, of which 891 were host proteins. To our knowledge, this is the most extensive intermixing of host and parasite proteins reported for tapeworm infections.Several antigens in cysticercosis, i.e., GP50, paramyosin and a calcium-binding protein were enriched in skeletal muscle cysts. Our results suggested the occurrence of tissue-enriched antigen that could be useful in the improvement of the immunodiagnosis for cysticercosis. Using several algorithms for epitope detection, we selected 42 highly antigenic proteins enriched for each tissue localization of the cysts. Taking into account the fold changes and the antigen/epitope contents, we selected 10 proteins and produced synthetic peptides from the best epitopes. Nine peptides were recognized by serum antibodies of cysticercotic pigs, suggesting that those peptides are antigens. Mixtures of peptides derived from SM and CNS cysts yielded better results than mixtures of peptides derived from a single tissue location, however the identification of the ‘optimal’ tissue-enriched antigens remains to be discovered. Through machine learning technologies, we determined that a reliable immunodiagnostic test for porcine cysticercosis required at least five different antigenic determinants. [ABSTRACT FROM AUTHOR]