Dataset Information

Triplex ELISA for Assessing Durability of Taenia solium Seropositivity after Neurocysticercosis Cure.

ABSTRACT: Neurocysticercosis prevalence estimates often are based on serosurveys. However, assessments of Taenia solium seropositivity durability in patients with various neurocysticercosis types are lacking. We optimized a triplex serologic ELISA by using synthetic GP50, T24H, and Ts18var3 antigens for T. solium. We used that assay to test sequential serologic responses over several years after neurocysticercosis cure in 46 patients, 9 each with parenchymal or ventricular neurocysticercosis and 28 with subarachnoid disease. Triplex results were concordant with 98% of positive and 100% of negative enzyme-linked immunoelectrotransfer blots. Eight years after neurocysticercosis cure, 11.1% of patients with parenchymal, 47.3% with subarachnoid, and 41.7% with ventricular disease were still seropositive. Median time to seroreversion after cure in this cohort in a T. solium nonendemic area was 2 years for parenchymal disease, 4 years for ventricular disease, and 8 years for subarachnoid disease. Our findings can inform epidemiologic models that rely on serosurveys to estimate disease burden.

SUBMITTER: Tang NL

PROVIDER: S-EPMC10310364 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Triplex ELISA for Assessing Durability of Taenia solium Seropositivity after Neurocysticercosis Cure.

Tang Nina L NL Nash Theodore E TE Corda Madelynn M Nutman Thomas B TB O'Connell Elise M EM

Emerging infectious diseases 20230701 7

Neurocysticercosis prevalence estimates often are based on serosurveys. However, assessments of Taenia solium seropositivity durability in patients with various neurocysticercosis types are lacking. We optimized a triplex serologic ELISA by using synthetic GP50, T24H, and Ts18var3 antigens for T. solium. We used that assay to test sequential serologic responses over several years after neurocysticercosis cure in 46 patients, 9 each with parenchymal or ventricular neurocysticercosis and 28 with s ...[more]

PMID: 37347506

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Project description:BackgroundEstimating 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.MethodsMortality, 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 findingsThe 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/significanceThis 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.

Project description:BackgroundTaenia 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.MethodsEpidemiological 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.ResultsIn 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.ConclusionsThis 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.

Project description:BackgroundTaenia 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 findingsSearches 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/significanceThe 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.

Project description:BackgroundThe ability of Taenia solium to modulate the immune system likely contributes to their longevity in the human host. We tested the hypothesis that the nature of the immune response is related to the location of parasite and clinical manifestations of infection.MethodologyPeripheral blood mononuclear cells (PBMC) were obtained from untreated patients with neurocysticercosis (NCC), categorized as having parenchymal or subarachnoid infection by the presence of cysts exclusively within the parenchyma or in subarachnoid spaces of the brain, and from uninfected (control) individuals matched by age and gender to each patient. Using multiplex detection technology, sera from NCC patients and controls and cytokine production by PBMC after T. solium antigen (TsAg) stimulation were assayed for levels of inflammatory and regulatory cytokines. PBMC were phenotyped by flow cytometry ex vivo and following in vitro stimulation with TsAg.Principal findingsSera from patients with parenchymal NCC demonstrated significantly higher Th1 (IFN-γ/IL-12) and Th2 (IL-4/IL-13) cytokine responses and trends towards higher levels of IL-1β/IL-8/IL-5 than those obtained from patients with subarachnoid NCC. Also higher in vitro antigen-driven TNF-β secretion was detected in PBMC supernatants from parenchymal than in subarachnoid NCC. In contrast, there was a significantly higher IL-10 response to TsAg stimulation in patients with subarachnoid NCC compared to parenchymal NCC. Although no differences in regulatory T cells (Tregs) frequencies were found ex vivo, there was a trend towards greater expansion of Tregs upon TsAg stimulation in subarachnoid than in parenchymal NCC when data were normalized for the corresponding controls.Conclusions/significanceT. solium infection of the subarachnoid space is associated with an enhanced regulatory immune response compared to infection in the parenchyma. The resulting anti-inflammatory milieu may represent a parasite strategy to maintain a permissive environment in the host or diminish inflammatory damage from the host immune response in the central nervous system.

Dataset Information

Triplex ELISA for Assessing Durability of Taenia solium Seropositivity after Neurocysticercosis Cure.

Publications

Triplex ELISA for Assessing Durability of Taenia solium Seropositivity after Neurocysticercosis Cure.

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