Guideline for Preventive Chemotherapy for the Control of Taenia solium Taeniasis

The larval stage of the parasite Taenia solium can encyst in the central nervous system causing neurocysticercosis, which is the main cause of acquired epilepsy in the countries in which the parasite is endemic. Endemic areas are those with the presence (or likely presence) of the full life cycle of Taenia solium. The parasite is most prevalent in poor and vulnerable communities in which pigs roam free, open defecation is practiced, basic sanitation is deficient, and health education is absent or limited. Several tools are available for the control of Taenia solium. Preventive chemotherapy for Taenia solium taeniasis, which is directed at the adult tapeworm, is one of them. Other tools focus on pig management, pig vaccination and treatment, sanitation and hygiene, and community education. Three potential drugs­niclosamide, praziquantel, and albendazole­have been considered for use for preventive chemotherapy in Taenia solium taeniasis control programs through mass drug administration or targeted chemotherapy. In this Guideline, we provide recommendations for preventive chemotherapy in Taenia solium-endemic areas using niclosamide, praziquantel, or albendazole, including at which dose and in which population groups. The development of this Guideline is based on the latest standard World Health Organization methods for guideline development, including the use of systematic search strategies, synthesis, quality assessment of the available evidence to support the recommendations, and participation of experts and stakeholders in the Guideline Development Group and External Review Group. The recommendations are intended for a wide audience, including policymakers and their expert advisers, and technical and program staff at governmental institutions and organizations involved in the planning, implementation, monitoring, and evaluation of preventive chemotherapy programs for the control of Taenia solium.

Guideline for preventive chemotherapy for the control of Taenia solium Taeniasis

The larval stage of the parasite Taenia solium can encyst in the central nervous system causing neurocysticercosis, which is the main cause of acquired epilepsy in the countries in which the parasite is endemic. Endemic areas are those with the presence (or likely presence) of the full life cycle of Taenia solium. The parasite is most prevalent in poor and vulnerable communities in which pigs roam free, open defecation is practiced, basic sanitation is deficient, and health education is absent or limited. Several tools are available for the control of Taenia solium. Preventive chemotherapy for Taenia solium taeniasis, which is directed at the adult tapeworm, is one of them. Other tools focus on pig management, pig vaccination and treatment, sanitation and hygiene, and community education. Three potential drugs­niclosamide, praziquantel, and albendazole­have been considered for use for preventive chemotherapy in Taenia solium taeniasis control programs through mass drug administration or targeted chemotherapy. In this Guideline, we provide recommendations for preventive chemotherapy in Taenia solium-endemic areas using niclosamide, praziquantel, or albendazole, including at which dose and in which population groups. The development of this Guideline is based on the latest standard World Health Organization methods for guideline development, including the use of systematic search strategies, synthesis, quality assessment of the available evidence to support the recommendations, and participation of experts and stakeholders in the Guideline Development Group and External Review Group. The recommendations are intended for a wide audience, including policymakers and their expert advisers, and technical and program staff at governmental institutions and organizations involved in the planning, implementation, monitoring, and evaluation of preventive chemotherapy programs for the control of Taenia solium. Guideline for Preventive Chemotherapy for the Control of Taenia solium Taeniasis

Control trial of porcine cysticercosis in Uganda using a combination of the TSOL18 vaccination and oxfendazole.

BACKGROUND: Neurocysticercosis caused by Taenia solium when the parasite lodges in the central nervous system, is an important cause of human seizures and mortality in sub-Saharan Africa. The parasite is prevalent in many regions of Uganda. Pigs are intermediate hosts for T. solium, and we evaluated a T. solium control program in pigs, involving vaccination of pigs with the TSOL18 vaccine and treatment with oxfendazole. METHODS: The study was conducted in two districts of Eastern Uganda involving the rural village communities of Bukedea (intervention area) and Kumi (control area) during 2016-2017. Seven hundred and thirty-four households were enrolled in the study. Pigs in the intervention area received intramuscular immunizations with TSOL18 (Cysvax™) and an oral medication with 30 mg/kg oxfendazole (Paranthic™) at approximately 3-monthly intervals for 18 months. Porcine cysticercosis was evaluated by post-mortem examination. At the beginning of the study, 111 pigs were examined. In an interim evaluation in the intervention area, 55 pigs were evaluated 12 months after starting the project. At the end of the study approximately 3 months after the final intervention, 55 pigs from the intervention area and 56 pigs from the control area were evaluated. RESULTS: The prevalence of porcine cysticercosis for the two sites was 16.2% at the beginning of the study (17.2% in the intervention area and 15.1% in the control area) with no statistically significant difference (P = 0.759) between the two study sites. Among the 110 animals assessed from the intervention site (55 at the interim evaluation and 55 at the final evaluation), no pig with viable T. solium cysts was found. There was a statistically significant difference between the prevalence at baseline (17.2%) and at the end of the study (0%) in the intervention area (P = 0.001) and a statistically significant difference between the intervention (0%) and control areas (5.4%) (P = 0.041) at the end of the study. CONCLUSIONS: Three-monthly concurrent vaccination of pigs with the TSOL18 vaccine and medication with oxfendazole eliminated T. solium transmission by the animals involved in the study. Application of vaccination with medication in pigs has the potential to reduce transmission of T. solium in Uganda and other endemic countries.

Cysticidal Therapy for Diffuse Parenchymal and Calcific Neurocysticercosis.

Antiparasitic treatment improves the prognosis for neurocysticercosis (NCC)-induced seizures. However, patients with high lesion loads are typically denied the possible benefit of cysticidal therapy because of fear of complications, and such patients are not represented in clinical trials involving cysticidal therapy. We provide proof of concept for combination treatment with dual antiparasitic therapy and corticosteroids in patients with diffuse lesions, including starry sky patterns, or calcific NCC. The safety and efficacy of treating patients with high lesion loads or calcific NCC should be tested in a randomized controlled trial.

Impact of a 3-year mass drug administration pilot project for taeniasis control in Madagascar.

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.

Unveiling Taenia solium kinome profile and its potential for new therapeutic targets.

Background: Helminth infections cause widespread morbidity and are a significant global disease burden. One among them is Neurocysticercosis, a central nervous system infection caused by the larvae Taenia solium, leading to epilepsy. Helminths are strong immune modulators and can survive for a long time in adverse host environments. Kinases are molecular switches and are essential to initiate/propagate signaling cascades and are detrimental to the regulation of homeostasis. They have been implicated in the progression of many diseases and are potentially lucrative drug targets.Objective: To identify kinases in T. solium proteome and prioritize them as drug targets.Methodology: A Hidden Markov Model (HMM) was used to curate and classify kinases into families based on sequence homology to model organisms followed by phylogenetic analysis of each family. To predict potential drug targets, kinases were identified based on a homologically lethal relationship to C. elegans but non-lethal to humans. Kinases thus selected were searched for matching ligands in SARFkinase and DrugBank databases.Result and conclusion: T. solium kinases make up 1.8% of its proteome, CMGC is the largest kinase family and RGC is the smallest and catalytically inactive family. We predict 23-potential kinases to be drug targets for T. solium.[Figure: see text].

Systematic review of the effectiveness of selected drugs for preventive chemotherapy for Taenia solium taeniasis.

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.

A longitudinal analysis of albendazole treatment effect on neurocysticercosis cyst evolution using multistate models.

BACKGROUND: In neurocysticercosis, the larval form of the pork tapeworm Taenia solium appears to evolve through three phases-active, degenerative and sometimes calcification-before disappearance. The antihelmintic drug, albendazole, has been shown to hasten the resolution of active cysts in neurocysticercosis. Little is known about the time cysts take to progress through each phase, with or without treatment. METHODS: We reconfigured brain imaging data from patient level to cyst level for 117 patients in a randomized clinical trial of albendazole in which images were taken at baseline, 1, 6, 12 and 24 mo. Applying a multistate model, we modelled the hazard of a cyst evolving to subsequent cyst phases before the next imaging (vs no change). We examined the impact of albendazole treatment overall and by patient and cyst characteristics on the hazard. RESULTS: Albendazole accelerated the evolution from the active to degenerative phase (HR=2.7, 95% CI 1.3 to 6.5) and from the degenerative phase to disappearance (HR=1.9, 95% CI 1.1 to 3.9). Albendazole's impact was stronger for patients who were male, did not have calcified cysts at baseline and who had multiple cysts in different locations. CONCLUSIONS: This research provides a better understanding of where in the cyst trajectory albendazole has the greatest impact.

Mathematical model of the life cycle of taenia-cysticercosis: transmission dynamics and chemotherapy (Part 1).

BACKGROUND: Taenia solium is the aetiological agent of human taeniasis, pig cysticercosis and human neurocysticercosis, which are serious public health problems, especially in developing countries. METHODS: A mathematical model of the transmission dynamics of taeniasis-cysticercosis is formulated. The model consists of a coupled system of differential equations, which are density-dependent equations for describing the flow of the parasite through the life cycle. The model is hybrid since it comprises deterministic equations with stochastic elements which describe changes in the mean parasite burden and incorporates the overall pattern of the parasites' distribution. RESULTS: Sensitivity and bifurcation analyses were carried out to determine the range of values of the model. The model can reproduce the observed epidemiological patterns of human taeniasis, pig and human cysticercosis. For example, for a wide range of parameter values, the mean intensity of adult worms tends to rapidly stabilize in one parasite per individual host. From this model, we also derived a Susceptible-Infected model to describe the prevalence of infection in humans and pigs. Chemotherapeutic interventions against pig cysticercosis or human taeniasis may reduce rapidly and effectively the mean intensity of human taeniasis, pig cysticercosis and human cysticercosis. This effect can be achieved even if the protective efficacy of the drug is of the order of 90% and the coverage rate is 90%. This means that health in humans infected either with adult worms or cysticerci may be achieved by the application of anthelmintic drugs against pig cysticercosis. However, treatment against human cysticercosis alone, does not influence neither human teniasis nor pig cysticercosis. This is because human cysticercosis infection does not influence the value of the basic reproductive number (Ro). CONCLUSIONS: Even coverage of 100% in the administration of anthelmintics did not eliminate the infection. Then elimination of the infection in all hosts does not seem a feasible goal to achieve by administering only chemotherapeutic interventions. Throughout the manuscript a discussion of our model in the context of other models of taeniasis-cysticercosis is presented.

A novel progesterone receptor membrane component (PGRMC) in the human and swine parasite Taenia solium: implications to the host-parasite relationship.

BACKGROUND: We have previously reported that progesterone (P4) has a direct in vitro effect on the scolex evagination and growth of Taenia solium cysticerci. Here, we explored the hypothesis that the P4 direct effect on T. solium might be mediated by a novel steroid-binding parasite protein. METHODS: By way of using immunofluorescent confocal microscopy, flow cytometry analysis, double-dimension electrophoresis analysis, and sequencing the corresponding protein spot, we detected a novel PGRMC in T. solium. Molecular modeling studies accompanied by computer docking using the sequenced protein, together with phylogenetic analysis and sequence alignment clearly demonstrated that T. solium PGRMC is from parasite origin. RESULTS: Our results show that P4 in vitro increases parasite evagination and scolex size. Using immunofluorescent confocal microscopy, we detected that parasite cells showed expression of a P4-binding like protein exclusively located at the cysticercus subtegumental tissue. Presence of the P4-binding protein in cyst cells was also confirmed by flow cytometry. Double-dimension electrophoresis analysis, followed by sequencing the corresponding protein spot, revealed a protein that was previously reported in the T. solium genome belonging to a membrane-associated progesterone receptor component (PGRMC). Molecular modeling studies accompanied by computer docking using the sequenced protein showed that PGRMC is potentially able to bind steroid hormones such as progesterone, estradiol, testosterone and dihydrodrotestosterone with different affinities. Phylogenetic analysis and sequence alignment clearly demonstrated that T. solium PGRMC is related to a steroid-binding protein of Echinoccocus granulosus, both of them being nested within a cluster including similar proteins present in platyhelminths such as Schistocephalus solidus and Schistosoma haematobium. CONCLUSION: Progesterone may directly act upon T. solium cysticerci probably by binding to PGRMC. This research has implications in the field of host-parasite co-evolution as well as the sex-associated susceptibility to this infection. In a more practical matter, present results may contribute to the molecular design of new drugs with anti-parasite actions.

TNF-α blockade suppresses pericystic inflammation following anthelmintic treatment in porcine neurocysticercosis.

BACKGROUND: Neurocysticercosis (NCC) is an infection of the brain with the larval cyst of the tapeworm, Taenia solium. Cysticidal treatment induces parasite killing resulting in a post inflammatory response and seizures, which generally requires corticosteroid treatment to control inflammation. The nature of this response and how to best control it is unclear. We investigated the anti-inflammatory effects of pretreatment with etanercept (ETN), an anti-tumor necrosis factor agent, or dexamethasone (DEX), a high potency corticosteroid, on the post treatment inflammatory response in naturally infected pigs with neurocysticercosis after a single dose of the cysticidal drug praziquantel (PZQ). METHODOLOGY/PRINCIPAL FINDINGS: We followed the methods from a previously developed treatment model of NCC in naturally infected swine. The four study groups of infected pigs included 3 groups treated with PZQ on day 0: PZQ-treated alone (100 mg/kg PO; n = 9), pretreated with dexamethasone (DEX, 0.2 mg/kg IM administered on days -1, +1 and +3; n = 6), and pretreated with etanercept (ETN, 25 mg IM per animal on days -7 and 0; n = 6). The fourth group remained untreated (n = 3). As measured by quantitative RT-PCR, ETN pretreatment depressed transcription of a wide range of proinflammatory, regulatory and matrix protease encoding genes at 120 hr post PZQ treatment in capsules of cysts that demonstrated extravasated Evans Blue (EB) (a measure of blood brain barrier dysfunction) compared to animals not receiving ETN. Transcription was significantly depressed for the proinflammatory genes tumor necrosis factor (TNF)-α, and interferon (IFN)-γ; the inflammation regulating genes cytotoxic T-lymphocyte-associated protein (CTLA)4, interleukin (IL)-13 and transforming growth factor (TGF)-ß; the tissue remodeling genes matrix metalloprotease (MMP)1 and 9, tissue inhibitors of metalloproteases (TIMP)1 and 2, and the genes regulating endothelial function vascular endothelial growth factor (VEGF)1, angiopoietin (Ang)1, Ang 2, and platelet endothelial cell adhesion molecule (PECAM)-1. In contrast, transcription was only modestly decreased in the DEX pretreated pigs compared to PZQ alone, and only for TNF-α, IL-6, IFN-γ, TGF-ß and Ang1. IL-10 was not affected by either ETN or DEX pretreatments. The degree of inflammation, assessed by semi-quantitative inflammatory scores, was modestly decreased in both ETN and DEX pretreated animals compared to PZQ treated pigs whereas cyst damage scores were moderately decreased only in cysts from DEX pretreated pigs. However, the proportion of cysts with EB extravasation was not significantly changed in ETN and DEX pretreated groups. CONCLUSIONS/SIGNIFICANCE: Overall, TNF-α blockade using ETN treatment modulated expression of a large variety of genes that play a role in induction and control of inflammation and structural changes. In contrast the number of inflammatory cells was only moderately decreased suggesting weaker effects on cell migration into the inflammatory capsules surrounding cysts than on release of modulatory molecules. Taken together, these data suggest that TNF-α blockade may provide a viable strategy to manage post-treatment pericystic inflammation that follows antiparasitic therapy for neurocysticercosis.

Effect of repeated mass drug administration with praziquantel and track and treat of taeniosis cases on the prevalence of taeniosis in Taenia solium endemic rural communities of Tanzania.

This study evaluated the effect of mass drug administration (MDA) with praziquantel administered to school-aged children (SAC) combined with 'track and treat' of taeniosis cases in the general population on the copro-antigen (Ag) prevalence of taeniosis. The study was conducted in 14 villages in Mbozi and Mbeya district, Tanzania. SAC made up 34% of the population and received MDA with praziquantel (40mg/kg) in 2012 (both districts) and in 2013 (Mbozi only). Three cross-sectional population-based surveys were performed in 2012 (R0), 2013 (R1), and 2014 (R2). In each survey approximately 3000 study subjects of all ages were tested for taeniosis using copro-Ag-ELISA. In total 9064 people were tested and copro-Ag-ELISA positive cases were offered treatment 6-8 months after sampling. The copro-Ag prevalence of taeniosis was significantly higher (Χ2-test, p=0.007) in Mbozi (3.0%) at R0 compared to Mbeya (1.5%). Twelve months after MDA in both districts (R1), the copro-Ag prevalence had dropped significantly in both Mbozi (2.0%, p=0.024) and in Mbeya (0.3%, p=0.004), but the significant difference between the districts persisted (Χ2-test, p<0.001). Ten months after the second round of MDA in Mbozi and 22 month after the first MDA (R2), the copro-Ag prevalence had dropped significantly again in Mbozi (0.8%, p<0.001), but had slightly increased in Mbeya (0.5%, p=0.051), with no difference between the two districts (Χ2-test, p=0.51). The taeniosis cases tracked and treated between round R0 and R2 represented 9% of the projected total number of taeniosis cases within the study area, based on the copro-Ag prevalence and village population data. Among SAC in Mbozi, infection significantly decreased at R1 (p=0.004, OR 0.12, CI: 0.02-0.41) and R2 (p=0.001, OR 0.24, CI: 0.09-0.53) when comparing to R0. In Mbeya infection significant decreased at R1 (p=0.013, OR 0.14, CI: 0.02-0.55), but no difference was found for R2 (p=0. 089), when comparing to R0 among SAC. This study showed that school-based MDA with praziquantel in combination with 'track and treat' of taeniosis cases significantly reduced the copro-Ag prevalence of taeniosis, and that annual MDA was significantly better than single MDA. The persistence of taeniosis cases illustrates that a One Health approach must be emphasized for effective control.

Assessment of a computer-based Taenia solium health education tool 'The Vicious Worm' on knowledge uptake among professionals and their attitudes towards the program.

Health education has been recognised as a specific intervention tool for control of Taenia solium taeniosis/cysticercosis but evaluation of the efficacy of the tool remains. The aim of our study was to assess the effect of a computer-based T. solium health education tool 'The Vicious Worm' on knowledge uptake among professionals and investigate attitudes towards the program. The study was carried out between March and May 2014 in Mbeya Region, Tanzania, where T. solium is endemic. The study was a pre and post assessment of a health education tool based on questionnaire surveys and focus group discussions to investigate knowledge and attitudes. A total of 79 study subjects participated in the study including study subjects from both health- and agriculture sector. The health education consisted of 1½h individual practice with the computer program. The baseline questionnaire showed an overall knowledge on aspects of acquisition and transmission of T. solium infections (78%), porcine cysticercosis treatment (77%), human tapeworm in general (72%), neurocysticercosis in general (49%), and porcine cysticercosis diagnosis (48%). However, there was a lack of knowledge on acquisition of neurocysticercosis (15%), prevention of T. solium taeniosis/cysticercosis (28%), and relation between porcine cysticercosis, human cysticercosis, and taeniosis (32%). Overall, the study subject's knowledge was significantly improved both immediately after (p=0.001) and two weeks after (p<0.001) the health education and knowledge regarding specific aspects was significantly improved in most aspects immediately after and two weeks after the health education. The focus group discussions showed positive attitudes towards the program and the study subjects found 'The Vicious Worm' efficient, simple, and appealing. The study revealed a good effect of 'The Vicious Worm' suggesting that it could be a useful health education tool, which should be further assessed and thereafter integrated in T. solium taeniosis/cysticercosis control.

Control of Taenia solium taeniasis/cysticercosis: The best way forward for sub-Saharan Africa?

Taenia solium taeniasis/cysticercosis is a neglected parasitic zoonosis with significant economic and public health impacts. Control measures can be broadly grouped into community health education, improvements in hygiene and sanitary conditions, proper meat handling at household and community level, improved standards of meat inspection, pig management, treatment of individual patients and possibly human populations, and treatment and/or vaccination of porcine populations. This manuscript looks critically into currently existing control options and provides suggestions on which (combination of) tools would be most effective in the control of T. solium taeniasis/cysticercosis in sub-Saharan Africa. Field data and disease transmission simulations suggest that implementation of a single intervention control strategy will not lead to a satisfactory reduction of disease morbidity or transmission. A feasible strategy to combat T. solium taeniasis/cysticercosis would include a combination of approaches focussing on both human (health education and treatment) and animal host (management, treatment and vaccination), which can vary for different communities and different geographical locations. Selection of the specific strategy depends on cost-effectiveness analyses based on solid field data, currently unavailable, though urgently needed; as well as on health priorities and resources of the country. A One Health approach involving medical, veterinary, environmental and social sectors is essential for T. solium to be controlled and eventually eliminated. Finally the success of any intervention is largely dependent on the level of societal and political acceptance, commitment and engagement.

Controlling Taenia solium and soil transmitted helminths in a northern Lao PDR village: Impact of a triple dose albendazole regime.

Taenia solium taeniasis-cysticercosis and soil-transmitted helminths (STHs) are parasitic Neglected Tropical Diseases endemic throughout Southeast Asia. Within Lao PDR, a remote northern hill tribe village had previously been identified as a hyper endemic focus for T. solium. To reduce this observed prevalence, a One Health intervention covering both pigs and humans was implemented, which included two Mass drug administrations (MDA1 and MDA2) for village residents using a triple dose albendazole 400mg treatment regime. In addition to the effect on T. solium levels, the dual impact of this anthelmintic regime on STHs within the community was also monitored. Faecal samples were collected pre and post MDA1 and MDA2 and analysed for the presence of Taenia species and the STHs Ascaris lumbricoides, Trichuris trichiura and hookworm species. The McMaster technique was used to measure the changes in both prevalence and intensity of infection. Molecular characterisation of Taenia and hookworm species was conducted to detect zoonotic species. The level of taeniasis within the sampled population decreased by 79.4% after MDA1, remained steady during the five month inter-treatment interval and decreased again by 100% after MDA2. The prevalence of STHs decreased by 65.5% and 62.8% after MDA1 and MDA2 respectively; however an increase to 62.1% of pre MDA1 levels was detected during the inter-treatment interval. Individually, hookworm prevalence decreased by 83.4% (MDA1) and 84.5% (MDA2), A. lumbricoides by 95.6% and 93.5% and T. trichiura by 69.2% and 61%. The intensity of infection within the sampled population also decreased, with egg reduction rates of 94.4% and 97.8% for hookworm, 99.4% and 99.3% for A. lumbricoides and 77.2% and 88.5% for T. trichiura. Molecular characterisation identified a T. solium tapeworm carrier from 21.6% (13/60) of households in the village. T. saginata was identified in 5% (3/60) of households. The zoonotic hookworm A. ceylanicum was detected in the resident dog population. These results suggest that the triple dose albendazole 400mg treatment regime achieved a significant reduction in the level of taeniasis whilst simultaneously reducing the STH burden within the village. The increased STH prevalence detected between MDAs reflects the need for behavioural changes and a sustained chemotherapy programme, which may also need to include the resident dog population.

Reprint of "Assessing the impact of a joint human-porcine intervention package for Taenia solium control: Results of a pilot study from northern Lao PDR".

Following confirmation that a remote village of approximately 300 inhabitants in northern Lao PDR was hyperendemic for the Neglected Tropical Disease Taenia solium, a pilot human-porcine therapeutic control intervention was implemented between October 2013 and November 2014. Mass drug administration with a three day albendazole 400mg protocol was offered to all eligible humans in October 2013 and March 2014. At these times, and again in October 2014, eligible village pigs received the anti-cysticercosis TSOL18 vaccination and an oral dose of oxfendazole anthelmintic at 30mg/kg, both repeated one month later. Community and individual human taeniasis prevalences were estimated via copro-antigen ELISA of volunteered human faecal samples prior to October 2013, and again in January 2015, in order to examine the short term impact of the intervention.

Cysticidal Efficacy of Combined Treatment With Praziquantel and Albendazole for Parenchymal Brain Cysticercosis.

BACKGROUND: The efficacy of current antiparasitic treatment for cerebral Taenia solium cysticercosis with either albendazole (ABZ) or praziquantel (PZQ) is suboptimal. A recent study demonstrated that combining these 2 antiparasitic drugs improves antiparasitic efficacy. We present here the parasiticidal efficacy data obtained during a previous phase II pharmacokinetic study that compared combined ABZ plus PZQ with ABZ alone. METHODS: The study was a randomized, double-blinded, placebo-controlled phase II evaluation of the pharmacokinetics of ABZ (15 mg/k/d, for 10 days) and PZQ (50 mg/k/d, for 10 days) in intraparenchymal brain cysticercosis. Patients received the usual concomitant medications, including an antiepileptic drug (phenytoin or carbamazepine), dexamethasone, and ranitidine. Randomization was stratified by antiepileptic drug. Patients underwent safety laboratory evaluations at days 4, 7, and 11, as well as magnetic resonance (MR) imaging at 6 months to assess parasiticidal efficacy. RESULTS: Thirty-two patients were included, 16 in each arm. All of them completed antiparasitic treatment and underwent follow-up brain MR imaging. Cysticidal efficacy was strikingly higher in the combined ABZ-plus-PZQ group than in the ABZ-alone group (proportion of cysts resolved, 78 of 82 [95%] vs 23 of 77 [30%] [relative risk {RR}, 3.18; 95% confidence interval {CI}, 2.08-4.88; P < .001]; patients with complete cyst clearance, 12 of 16 [75%] vs 4 of 16 [25%] [RR, 3.00; 95% CI, 1.23-7.34; P = .005]). CONCLUSIONS: The combination of ABZ plus PZQ is more effective in destroying viable brain cysticercosis cysts than ABZ alone. CLINICAL TRIALS REGISTRATION: NCT00441285.

Monitoring the outcomes of interventions against Taenia solium: options and suggestions.

There is an increasing interest in reducing the incidence of human neurocysticercosis, caused by infection with the larval stage of Taenia solium. Several intervention trials are currently assessing various options for control of T. solium transmission. A critical aspect of these trials will be the evaluation of whether the interventions have been successful. However, there is no consensus about the most appropriate or valuable methods that should be used. Here, we undertake a critical assessment of the diagnostic tests which are currently available for human T. solium taeniasis and human and porcine cysticercosis, as well as their suitability for evaluation of intervention trial outcomes. Suggestions are made about which of the measures that are available for evaluation of T. solium interventions would be most suitable, and which methodologies are the most appropriate given currently available technologies. Suggestions are also made in relation to the most urgent research needs in order to address deficiencies in current diagnostic methods.

Immune response to Taenia solium cysticerci after anti-parasitic therapy.

Albendazole is the drug of choice for Taenia solium infection. Concomitant administration of steroid has been advocated to avoid adverse reactions to albendazole therapy in neurocysticercosis. Some T. solium cysticerci (larvae) respond to albendazole therapy while others do not and the reasons remain unexplained. We hypothesise that the immune response differs between treatment responder and non-responder cysticerci and this may determine the outcome. Twenty swine naturally infected with T. solium were purchased from the market and the infection was confirmed by magnetic resonance imaging. Swine were divided into two groups; swine in group 1 were treated with albendazole and those in group 2 were treated with albendazole plus steroid (prednisolone). All the animals underwent follow-up MRIs at 6 and 12 weeks after start of therapy and were then sacrificed. Tissues surrounding the cysticerci were collected and studied for the expression of different cytokines by reverse transcriptase PCR and ELISA. Albendazole therapy was found to be more effective in parasite killing than albendazole plus steroid (94.11% versus 70.96%, P=0.011). Albendazole therapy provoked a pro-inflammatory, Th1 (IFN-γ) and pleiotropic (IL-6) cytokine response around the dead cysticerci. Despite a heavy parasite burden in the brain, all the pigs treated with albendazole plus steroid survived. In this group of animals, a mixed pro-inflammatory Th1, Th2 (IL-4) and regulatory cytokine (IL-10) response was associated with responder cysticerci. Further, Th2 and regulatory cytokine responses were associated with non-responder cysticerci.