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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.
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Cisticercose , Fezes , Doenças dos Suínos , Taenia solium , Animais , Zâmbia/epidemiologia , Taenia solium/isolamento & purificação , Humanos , Projetos Piloto , Suínos , Doenças dos Suínos/transmissão , Doenças dos Suínos/parasitologia , Doenças dos Suínos/prevenção & controle , Fezes/parasitologia , Cisticercose/transmissão , Cisticercose/veterinária , Cisticercose/prevenção & controle , Feminino , Masculino , Adulto , Adolescente , Pessoa de Meia-Idade , Adulto Jovem , Teníase/transmissão , Teníase/prevenção & controle , Teníase/parasitologia , Teníase/veterinária , Criança , Erradicação de Doenças/métodos , Anti-Helmínticos/uso terapêutico , Anti-Helmínticos/administração & dosagemRESUMO
A hallmark of Alzheimer's disease (AD) is the extracellular aggregation of toxic amyloid-beta (Aß) peptides in form of plaques. Here, we identify netoglitazone, an antidiabetic compound previously tested in humans, as an Aß aggregation antagonist. Netoglitazone improved cognition and reduced microglia activity in a mouse model of AD. Using quantitative whole-brain three-dimensional histology (Q3D), we precisely identified brain regions where netoglitazone reduced the number and size of Aß plaques. We demonstrate the utility of Q3D in preclinical drug evaluation for AD by providing a high-resolution brain-wide view of drug efficacy. Applying Q3D has the potential to improve pre-clinical drug evaluation by providing information that can help identify mechanisms leading to brain region-specific drug efficacy.
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BACKGROUND: This study aimed at describing the epidemiology of (neuro)cysticercosis as well as its clinical and radiological characteristics in a Taenia solium endemic district of Zambia. METHODS: This was part of a cross-sectional community-based study conducted in Sinda district to evaluate an antibody-detecting T. solium point-of-care (TS POC) test for taeniosis and (neuro)cysticercosis. All TS POC cysticercosis positive (CC+) participants and a subset of the TS POC cysticercosis negative (CC-) received a clinical evaluation and cerebral computed tomography (CT) examination for neurocysticercosis (NCC) diagnosis and staging. RESULTS: Of the 1249 participants with a valid TS POC test result, 177 (14%) were TS POC CC+ . Cysticercosis sero-prevalence was estimated to be 20.1% (95% confidence intervals [CI] 14.6-27.0%). In total, 233 participants received a CT examination (151 TS POC CC+ , 82 TS POC CC-). Typical NCC lesions were present in 35/151 (23%) TS POC CC+ , and in 10/82 (12%) TS POC CC- participants. NCC prevalence was 13.5% (95% CI 8.4-21.1%) in the study population and 38.0% (95% CI 5.2-87.4%) among people reporting epileptic seizures. Participants with NCC were more likely to experience epileptic seizures (OR = 3.98, 95% CI 1.34-11.78, p = 0.01) than those without NCC, although only 7/45 (16%) people with NCC ever experienced epileptic seizures. The number of lesions did not differ by TS POC CC status (median: 3 [IQR 1-6] versus 2.5 [IQR 1-5.3], p = 0.64). Eight (23%) of the 35 TS POC CC+ participants with NCC had active stage lesions; in contrast none of the TS POC CC- participants was diagnosed with active NCC. CONCLUSION: NCC is common in communities in the Eastern province of Zambia, but a large proportion of people remain asymptomatic.
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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.
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Agentes Comunitários de Saúde , Cisticercose , Conhecimentos, Atitudes e Prática em Saúde , Taenia solium , Humanos , Agentes Comunitários de Saúde/educação , Adulto , Animais , Ruanda/epidemiologia , Feminino , Masculino , Taenia solium/isolamento & purificação , Estudos Transversais , Cisticercose/epidemiologia , Cisticercose/prevenção & controle , Cisticercose/parasitologia , Pessoa de Meia-Idade , Adulto Jovem , Idoso , Educação em Saúde/métodos , SoftwareRESUMO
BACKGROUND: Epilepsy is a multifactorial neurological disorder, including parasitic infections of the brain such as neurocysticercosis (NCC). People with epileptic seizures (PWES) in low and middle-income countries often do not receive appropriate treatment, which besides epileptic seizures, may also lead to reduced quality of life and possibly death. The objective of this study was to describe gaps in treatment of epileptic seizures in a Zambian rural area. METHODS: A cross-sectional study was conducted in Sinda district of Zambia between August and October 2018. PWES identified from clinic records and with the help of community healthcare workers were recruited. Two questionnaires, one to PWES and the other to local healthcare workers, were administered to describe the treatment gap. RESULTS: A total of 146 PWES and 43 healthcare workers were interviewed. Of the 146 PWES, 131 had taken anti-seizure medication (ASM) at some point since their seizure onset, of which 49.6% were on current treatment. Only 18.3% were on continuous ASM, an overall treatment gap of 83.6%. Over 55% of healthcare workers did not know the relationship between epilepsy and NCC. The risk factors associated with lack of appropriate treatment were stock-outs of ASMs, lack of diagnostic equipment, poor patient follow-up, and PWES opting for traditional medicine. CONCLUSION: The treatment gap is substantial in Sinda district. The causes are multifactorial, involving shortcomings at the level of healthcare facilities, communities, and individuals. Directed training of healthcare workers and significant improvements in the supply and dispensing of ASMs will be key in substantially reducing the gap.
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Anticonvulsivantes , Epilepsia , População Rural , Humanos , Zâmbia/epidemiologia , Estudos Transversais , Feminino , População Rural/estatística & dados numéricos , Masculino , Adulto , Epilepsia/terapia , Epilepsia/epidemiologia , Pessoa de Meia-Idade , Anticonvulsivantes/uso terapêutico , Adulto Jovem , Adolescente , Convulsões/terapia , Convulsões/epidemiologia , Convulsões/diagnóstico , Neurocisticercose/complicações , Neurocisticercose/epidemiologia , Neurocisticercose/terapia , Criança , Pessoal de Saúde/estatística & dados numéricosRESUMO
BACKGROUND: There is increasing epidemiological evidence supporting the association between onchocerciasis and seizures, reinforcing the concept of onchocerciasis-associated epilepsy (OAE). The aim of this paper is to provide an update on the new knowledge about OAE and to propose recommendations to the World Health Organization how to address this public health problem. MAIN TEXT: During the 2nd International Workshop on OAE held on 19-21 September, 2023, in Antwerp, Belgium, participants recognised OAE as a substantial yet neglected public health problem, particularly in areas of sub-Saharan Africa where onchocerciasis remains hyperendemic. Evidence from prospective population-based studies suggest that strengthening onchocerciasis elimination efforts leads to a significant reduction of OAE incidence. There is a need to validate an OAE case definition to estimate the burden of disease and identify onchocerciasis-endemic areas requiring intensification of onchocerciasis elimination programmes and integration of epilepsy care. It is expected that raising awareness about OAE will boost the population uptake of ivermectin. The implementation of a community-based epilepsy treatment programme offering free anti-seizure medications (ASMs) has shown high effectiveness in reducing the frequency of seizures and improving the overall quality of life of people with epilepsy. CONCLUSIONS: To reduce OAE burden, enhanced collaboration between onchocerciasis and mental health programmes at community, national, and international levels is required. Urgent efforts are needed to ensure the uninterrupted provision of free ASMs in onchocerciasis-endemic areas. Furthermore, OAE should be included in the quantification of the onchocerciasis disease burden.
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Epilepsia , Oncocercose , Humanos , Oncocercose/complicações , Oncocercose/tratamento farmacológico , Oncocercose/epidemiologia , Estudos Prospectivos , Qualidade de Vida , Prevalência , Ivermectina/uso terapêutico , Epilepsia/epidemiologia , Epilepsia/prevenção & controle , Epilepsia/tratamento farmacológicoRESUMO
BACKGROUND: Neurocysticercosis is a common cause of epilepsy in Taenia solium-endemic areas in sub-Saharan Africa but is often undiagnosed because of an absence of affordable diagnostic tools. This study evaluated the diagnostic accuracy of a T solium cysticercosis antibody-detecting lateral-flow point-of-care assay (TS POC test) for the neuroimaging-based diagnosis of neurocysticercosis. METHODS: Patients with epileptic seizures or severe progressive headache were recruited consecutively from three hospitals in southern Tanzania. All patients were tested with the TS POC test. All patients positive for cysticercosis on the TS POC test and every tenth patient who was negative for cysticercosis received a brain CT examination and underwent reference testing for T solium cysticercosis (ie, rT24H-EITB, LLGP-EITB, and antigen ELISA). The primary outcome of the study was the sensitivity of the TS POC test for the diagnosis of neurocysticercosis. FINDINGS: Of the 601 recruited participants, 102 (17%) tested positive for cysticercosis with the TS POC test. Overall, 48 (62%) of the 77 patients positive for cysticercosis and five (17%) of the 29 patients negative for cysticercosis on the TS POC test had CT-confirmed neurocysticercosis. The TS POC test yielded a sensitivity of 49% (uncertainty interval [UI] 41-58) for neurocysticercosis. Sensitivity was similar to that of the rT24H-EITB (44%, UI 37-51) and the antigen ELISA (50%, 43-56). For the subset of neurocysticercosis cases with at least one active (ie, vesicular) lesion, sensitivity was above 98% for the TS POC test, the rT24H-ETIB, and the antigen ELISA. INTERPRETATION: The TS POC test showed promising results for the diagnosis of neurocysticercosis in patients with vesicular lesions, which need to be confirmed in a larger study. This test could be considered to support policies on screening patients with suspected neurocysticercosis in clinical settings, which would allow appropriate referral for neuroimaging and early treatment. FUNDING: German Federal Ministry of Education and Research and the European & Developing Countries Clinical Trials Partnership. TRANSLATION: For the Swahili translation of the abstract see Supplementary Materials section.
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Cisticercose , Epilepsia , Neurocisticercose , Taenia solium , Animais , Humanos , Neurocisticercose/diagnóstico , Tanzânia , Cisticercose/diagnóstico , Testes ImediatosRESUMO
Parasite aggregation within hosts is a fundamental feature of parasite distributions, whereby the majority of parasites are harboured by a minority of hosts. Parasite aggregation can influence their transmission and hence control. In this narrative review, possible sources of aggregation of Taenia solium cysticerci in pigs are discussed, along with implications for control of the parasite. While heavy T. solium infections in pigs could most likely be associated with ingestion of high doses of infective parasite eggs, consistent with coprophagic behaviour of pigs, lighter infections indicate a role of indirect routes of transmission to pigs, mostly from lower infection doses. Light infections are likely to be missed by commonly used diagnostic methods - tongue examination or meat inspection - and end up in the food chain. Hence, they entail a 'hidden' risk and are of a particular public health concern, especially in areas where meat is consumed raw or undercooked. To be effective and sustainable, control strategies against T. solium likely require a broader understanding of, and consideration for parasite transmission dynamics. More importantly, a holistic One Health approach incorporating interventions on humans, pigs and the environment will likely have a larger, more successful and sustainable impact.
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Effective public health measures against SARS-CoV-2 require granular knowledge of population-level immune responses. We developed a Tripartite Automated Blood Immunoassay (TRABI) to assess the IgG response against three SARS-CoV-2 proteins. We used TRABI for continuous seromonitoring of hospital patients and blood donors (n = 72'250) in the canton of Zurich from December 2019 to December 2020 (pre-vaccine period). We found that antibodies waned with a half-life of 75 days, whereas the cumulative incidence rose from 2.3% in June 2020 to 12.2% in mid-December 2020. A follow-up health survey indicated that about 10% of patients infected with wildtype SARS-CoV-2 sustained some symptoms at least twelve months post COVID-19. Crucially, we found no evidence of a difference in long-term complications between those whose infection was symptomatic and those with asymptomatic acute infection. The cohort of asymptomatic SARS-CoV-2-infected subjects represents a resource for the study of chronic and possibly unexpected sequelae.
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Many efforts targeting amyloid-ß (Aß) plaques for the treatment of Alzheimer's Disease thus far have resulted in failures during clinical trials. Regional and temporal heterogeneity of efficacy and dependence on plaque maturity may have contributed to these disappointing outcomes. In this study, we mapped the regional and temporal specificity of various anti-Aß treatments through high-resolution light-sheet imaging of electrophoretically cleared brains. We assessed the effect on amyloid plaque formation and growth in Thy1-APP/PS1 mice subjected to ß-secretase inhibitors, polythiophenes, or anti-Aß antibodies. Each treatment showed unique spatiotemporal Aß clearance, with polythiophenes emerging as a potent anti-Aß compound. Furthermore, aligning with a spatial-transcriptomic atlas revealed transcripts that correlate with the efficacy of each Aß therapy. As observed in this study, there is a striking dependence of specific treatments on the location and maturity of Aß plaques. This may also contribute to the clinical trial failures of Aß-therapies, suggesting that combinatorial regimens may be significantly more effective in clearing amyloid deposition.
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Doença de Alzheimer , Microscopia , Camundongos , Animais , Camundongos Transgênicos , Peptídeos beta-Amiloides/metabolismo , Doença de Alzheimer/tratamento farmacológico , Encéfalo/metabolismo , Placa Amiloide/tratamento farmacológico , Modelos Animais de Doenças , Precursor de Proteína beta-Amiloide , Presenilina-1/farmacologiaRESUMO
OBJECTIVES: Neurocysticercosis (NCC) is a parasitic disease caused by the larval stage of the tapeworm Taenia solium. NCC mainly occurs in Africa, Latin America and South-East Asia and can cause a variety of clinical signs/symptoms. Although it is a rare disease in Europe, it should nonetheless be considered as a differential diagnosis. The aim of this study was to describe clinical characteristics and management of patients with NCC diagnosed and treated in Europe. METHODS: We conducted a systematic search of published and unpublished data on patients diagnosed with NCC in Europe (2000-2019) and extracted demographic, clinical and radiological information on each case, if available. RESULTS: Out of 293 identified NCC cases, 59% of patients presented initially with epileptic seizures (21% focal onset); 52% presented with headache and 54% had other neurological signs/symptoms. The majority of patients had a travel or migration history (76%), mostly from/to Latin America (38%), Africa (32%) or Asia (30%). Treatment varied largely depending on cyst location and number. The outcome was favorable in 90% of the cases. CONCLUSIONS: Management of NCC in Europe varied considerably but often had a good outcome. Travel and migration to and from areas endemic for T. solium will likely result in continued low prevalence of NCC in Europe. Therefore, training and guidance of clinicians is recommended for optimal patient management.
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Neurocisticercose , Taenia solium , Animais , Humanos , Neurocisticercose/diagnóstico , Neurocisticercose/tratamento farmacológico , Neurocisticercose/epidemiologia , Estudos Retrospectivos , Europa (Continente) , PrevalênciaRESUMO
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.
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Neurocisticercose , Humanos , Neurocisticercose/complicações , Neurocisticercose/diagnóstico por imagem , Neurocisticercose/epidemiologia , Estudos Transversais , Tanzânia/epidemiologia , Radiografia , Convulsões/diagnóstico por imagem , Convulsões/epidemiologiaRESUMO
BACKGROUND: Taenia solium cysticercosis is a zoonotic disease that is endemic in many low- and middle-income countries where risk factors for disease transmission are present. The economic impact of cysticercosis on public health and on the pig production sector is not well known in many of those countries, including Burundi. This study aimed at estimating the burden of T. solium cysticercosis in Burundi including data on humans and pigs. METHODS: Epidemiological and economic data were collected from literature up to July 30, 2021 and governmental and non-governmental agencies. Direct and indirect costs for neurocysticercosis (NCC)-associated epilepsy and losses due to porcine cysticercosis were estimated to assess the economic burden, while the health burden was estimated using zoonotic disability-adjusted life years (zDALYs). Different probability distributions (Uniform, Beta, Dirichlet and Gamma) were applied depending on the type of epidemiological parameter. Monte Carlo simulations and 100,000 iterations were used to calculate the 95% uncertainty interval (UI) for each parameter and perform sensitivity analyses. RESULTS: In Burundi, 4.26 million USD (95% UI, 1,858,308-8,190,951) were estimated as economic impact due to T. solium cysticercosis in humans and pigs, of which 40.2% (95% UI, 10.3-75.1) of the total costs were due to NCC-associated epilepsy and 59.8% (95% UI, 24.9-89.7) of the losses due to porcine cysticercosis. The cost per NCC-associated epilepsy case was 72 USD (95% UI, 25-168), representing 30.8% of the GDP per capita in 2020. The probable incident cases and deaths for NCC-associated epilepsy were 9065 (95% UI, 2370-16,716) and 61 (95% UI, 16-114), respectively. More than 2 zDALYs (95% UI, 1.1-3.4) per thousand person-years was estimated, of which an average of 1.3 DALYs [0;0] (95% UI, 0.3-2.6) was due to NCC- associated epilepsy and 0.8 animal loss equivalents (ALEs) (95% UI, 0.3-1.5) due to porcine cysticercosis. CONCLUSIONS: This study provides evidence of a significant burden of T. solium cysticercosis for Burundi's population. We urge policy makers to use these evidence-based results and put T. solium cysticercosis on the public health agenda of the country. This study recommends urgent action to find solutions for integrated control strategies for T. solium cysticercosis in Burundi.
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Cisticercose , Epilepsia , Neurocisticercose , Doenças dos Suínos , Taenia solium , Humanos , Suínos , Animais , Burundi/epidemiologia , Doenças dos Suínos/epidemiologia , Prevalência , Cisticercose/epidemiologia , Cisticercose/veterinária , Neurocisticercose/epidemiologia , Epilepsia/epidemiologiaRESUMO
BACKGROUND: Taenia solium typically affects resource-poor communities where pigs are allowed to roam freely, and sanitation and hygiene levels are suboptimal. Sustainable, long-term strategies are urgently needed to control the disease. Geographically targeted interventions, i.e. screening or treatment of taeniosis among people living near infected pigs (defined as ring screening and ring treatment, respectively), have been shown to be effective control options in Peru. However, these results might not be directly generalizable to sub-Saharan African settings. Pig movements play a vital role in the transmission and, consequently, the success of ring interventions against T. solium. The aim of the present study was to explore roaming patterns of pigs in T. solium endemic communities in Zambia as a first step toward evaluating whether ring interventions should be considered as a treatment option in Zambia. METHODS: In total, 48 free-roaming pigs in two rural neighborhoods in the Eastern Province of Zambia were tracked using a Global Positioning System (GPS) receiver. Tracking took place in April (end of the rainy season) 2019 and October (end of the dry season) 2019. The number of revisitations and the time spent within rings of different radii (50, 100 and 250 m) around the coordinates of each pig owner's household were calculated for each pig. RESULTS: The total tracking time for 43 pigs in the final analysis set ranged between 43 and 94 h. Pigs spent a median of 31% and 13% of the tracked time outside the 50- and 100-m radius, respectively, although large variations were observed between pigs. Overall, 25 pigs (58%) went outside the 250-m ring at least once, and individual excursions lasting up to 16 h were observed. In the dry season, 17 out of 23 pigs went outside the 250-m radius compared to only eight out of 20 pigs in the rainy season (P = 0.014). CONCLUSIONS: In our study sites in Zambia, the majority of pigs spent most of their time within 50 or 100 m of their owner's home, and these results are comparable with those on Peruvian pigs. Both radii could therefore be considered reasonable options in future ring interventions.
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Cisticercose , Doenças dos Suínos , Taenia solium , Animais , Cisticercose/epidemiologia , Humanos , População Rural , Suínos , Doenças dos Suínos/epidemiologia , Doenças dos Suínos/prevenção & controle , Zâmbia/epidemiologiaRESUMO
OBJECTIVE: Neurocysticercosis (NCC), caused by the pork tapeworm Taenia solium, is a major cause of acquired epilepsy in endemic regions. The Republic of Uganda, one of the great-lakes nations in East Africa, has undergone major strives of political instability in the past century, impeding control of T. solium and other foodborne diseases. Building on data on the epidemiology of NCC, we aimed to assess the health and economic impact of NCC-associated epilepsy and headache in Uganda. METHODS: We used DisMod II to generate an internally consistent, complete and age-stratified set of epidemiological parameters for NCC epilepsy, and subsequently modelled the NCC headache incidence from the NCC epilepsy incidence. The health impact of both conditions was quantified in terms of Disability-Adjusted Life Years (DALYs), while the economic impact was quantified as the cost of illness associated with direct healthcare costs, patient costs and productivity losses. For both assessments, we adopted an incidence perspective and used 2010 as reference year. Uncertainty was propagated using 100,000 Monte Carlo simulations. RESULTS: In 2010, NCC was estimated to cause more than 9000 (CI: 7685-11,071) new cases of epilepsy and nearly 1500 new cases of headache, eventually leading to nearly 3000 deaths. Overall, it was estimated that NCC led to more than 170,000 DALYs (5.2 per 1000 person years; 16 per incident case) and an economic loss of more than USD 75 million (8000 per incident case). Non-fatal health outcomes were the largest contributors to the overall health impact, while productivity losses dominated the NCC cost of illness. CONCLUSIONS: NCC imposes a substantial burden on public health and the economy in Uganda with poor attention given to this public health problem. Increased awareness among governments, international agencies, and general public, as well as targeted intervention studies using a One Health approach are needed to reduce the significant burden of NCC in Uganda.
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Neurocisticercose/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Efeitos Psicossociais da Doença , Feminino , Custos de Cuidados de Saúde , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Neurocisticercose/economia , Prevalência , Uganda/epidemiologia , Adulto JovemRESUMO
Taenia solium taeniosis diagnosis is challenging because current tests perform sub-optimally and/or are expensive, require sophisticated equipment, infrastructure and trained manpower, and therefore are not community deployable. A recently-developed, multi-strip, T. solium point-of-care test (TS POC) for simultaneous detection of tapeworm (TS POC T) and cysticercus (TS POC CC) human antibodies was evaluated for diagnostic accuracy on consecutively recruited community participants in Sinda district, Zambia. All participants were tested using the TS POC test. All test-positives and 20% of the test-negative participants were invited to give a blood and stool sample for reference testing. Three different reference tests were used for taeniosis diagnosis: recombinant rES33 enzyme-linked immunoelectrotransfer blot (rES33 EITB), copro PCR and copro Ag ELISA. Bayesian analysis with probabilistic constraints was used to estimate sensitivity and specificity. In total, 1254 participants were tested with the TS POC test, of whom 13 tested positive using the TS POC T. Based on 161 participants with complete data, the estimated sensitivity and specificity for the TS POC T test were 38% (95% CI: 5-93%) and 99% (95% CI: 98-100%), respectively. The challenge of highly variable inter-assay performance is highlighted. We recommend either increasing the sensitivity or redesigning the test.
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The lack of cheap, easy-to-use, rapid diagnostic tests has led to the development of several rapid diagnostic tests for cysticercosis. The new prototype two-strip, Taenia solium point of care test (TS POC) detects antibodies against taeniosis (TS POC T) and cysticercosis (TS POC CC). This study evaluated the diagnostic performance of the TS POC CC in the Sinda district in eastern Zambia. A sample of 1254 participants was recruited and tested with the TS POC. Out of the 1249 participants with a valid TS POC result, 177 (14%) tested positive while 1072 (86%) tested negative. All individuals with a positive TS POC and a subset of negative TS POC participants were selected for serum sampling, and were subjected to the recombinant glycoprotein T24H enzyme-linked immunoelectrotransfer blot (rT24H EITB) and the serum B60/158 (serum Ag) enzyme-linked immunosorbent assay (Ag ELISA). Performance characteristics were estimated using a Bayesian approach with probabilistic constraints. Based on 255 complete cases, the estimated sensitivity and specificity of the TS POC CC test were 35% (95% CI: 14-63%) and 87% (95% CI: 83-90%), respectively. The diagnostic performance needs to be improved, possibly by titrating antigen and other reagents' concentration in the strip to produce a performance similar to existing cysticercosis tests such as the rT24H EITB.
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Taenia solium diagnosis is challenging as trained personnel, good diagnostic tools, and infrastructure is lacking in resource-poor areas. This paper aims to describe the study trial design adopted to evaluate a newly developed rapid point-of-care test that simultaneously detects taeniosis and neurocysticercosis (TS POC) in three district hospitals in Tanzania. The two-stage design included three types of patients: patients with specific neurological signs and symptoms (group 1); patients with complaints compatible with intestinal worm infections (group 2); patients with other symptom(s) (group 3). For group 1, all patients were tested using the TS POC test (stage 1), after which all positive, and a subset of negative, patients were selected for laboratory reference tests, clinical examination, and a brain computed tomography (CT) scan (stage 2). For groups 2 and 3, a similar design was adopted, but clinical examination and a brain CT scan (stage 2) were only performed in patients who were TS POC test-positive for cysticercosis. Due to the lack of a gold standard, a Bayesian approach was used to determine test accuracy for taeniosis and cysticercosis. For neurocysticercosis, a composite case definition was used as the reference standard. If successful, this study will help the future developments (commercialization and implementation) of the rapid test and improve patient management and disease prevention.
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Field-applicable, high-quality, and low-cost diagnostic tools are urgently needed for Taenia solium. The aim of this paper is to describe the design, challenges, and rationale for the design of a diagnostic accuracy study in low-resource community settings in Zambia. The trial was designed as a prospective study with a two-stage design to evaluate a new point-of-care test (TS POC) for the detection of taeniosis and (neuro)cysticercosis. Participants within randomly selected households were tested with the TS POC test (index test). Participants who tested TS POC positive for taeniosis and/or cysticercosis and a subset of the negatives were requested to give blood and stool samples for reference testing, and to undergo clinical examination and a cerebral CT scan. The difficulties of conducting a clinical trial in settings with limited research and neuroimaging infrastructure as well as peculiarities specifically related to the disease (low prevalence of taeniosis and the lack of a gold standard) were taken into consideration for the design of this study. The two-stage design increased the efficiency of the study by reducing the number of samples, clinical examinations, and CT scans. Simplified flows and sampling processes were preferred over complex follow-up and randomization systems, aiming to reduce bias and increase the generalizability of the study.
RESUMO
BACKGROUND: Diagnostic test evaluation includes measures of performance and assessment of operational characteristics. The latter focuses on end-user understanding of instructions to perform the test, ease of use, test turnaround time and ease of result interpretation. This study aimed to assess user comprehension of training for and ease of use of a Taenia solium point of care test (TS POC) evaluated in a community and hospital setting in Zambia and Tanzania, respectively. METHODS: The TS POC is a three-step in-house-produced rapid diagnostic test (RDT) for the simultaneous detection of taeniosis (TST) and cysticercosis (TSCC) antibodies. Data collected by administering questionnaires to 29 end-users and from the main evaluation database was analyzed quantitatively. RESULTS: End-users (28/29, 97%) perceived that the training they received for performing the test was sufficient. They performed 4080 tests, of which 80 were invalid. The community-based study and TST tests had higher invalid rates. The overall result interpretation was within the acceptable range of RDTs with an overall disagreement between readers of 3.3%. The Kappa coefficient of agreement was 85 and 82% for TSCC and TST, respectively. There was more disagreement among readers in the community-based study. CONCLUSION: End-users rated the TS POC kit moderate in terms of ease of use citing long test turnaround time and difficulties in using the blood transfer device. Overall, the operational performance of the TS POC kit and end-users was within the established acceptable performance range.