Dataset Information

Changes in Cytokine, Filarial Antigen, and DNA Levels Associated With Adverse Events Following Treatment of Lymphatic Filariasis.

ABSTRACT:

Background

Mild to moderate adverse events (AEs) are common after treatment of lymphatic filariasis (LF) and pose a major challenge for the global LF elimination program. We studied changes in cytokine levels and filarial worm components in plasma of subjects with and without AEs following treatment of LF.

Methods

Participants (n = 24) were hospitalized and monitored for AEs following treatment. Cytokines (27), filarial DNA, circulating filarial antigen (CFA), and immune complexes were measured in plasma samples collected before and after treatment.

Results

Levels for 16 cytokines increased after treatment in individuals with moderate AEs compared to individuals with no and/or mild AEs. These included 3 major proinflammatory cytokines (interleukin 6, tumor necrosis factor α, and interleukin 1β). Eotaxin-1 levels were elevated at baseline in individuals who developed moderate AEs after treatment; thus, eotaxin-1 is a potential biomarker for AE risk. CFA and filarial DNA levels increased more in individuals with moderate AEs after treatment than in people with no/mild AEs.

Conclusions

Increases in cytokine, filarial DNA, and CFA levels were associated with development of AEs following treatment of LF. Improved understanding of the pathogenesis of AEs may lead to improved methods for their prevention or management that could increase compliance in elimination programs.

SUBMITTER: Andersen BJ

PROVIDER: S-EPMC5853815 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Publications

Changes in Cytokine, Filarial Antigen, and DNA Levels Associated With Adverse Events Following Treatment of Lymphatic Filariasis.

Andersen Britt J BJ Kumar Jessica J Curtis Kurt K Sanuku Nelly N Satofan Samson S King Christopher L CL Fischer Peter U PU Weil Gary J GJ

The Journal of infectious diseases 20180101 2

<h4>Background</h4>Mild to moderate adverse events (AEs) are common after treatment of lymphatic filariasis (LF) and pose a major challenge for the global LF elimination program. We studied changes in cytokine levels and filarial worm components in plasma of subjects with and without AEs following treatment of LF.<h4>Methods</h4>Participants (n = 24) were hospitalized and monitored for AEs following treatment. Cytokines (27), filarial DNA, circulating filarial antigen (CFA), and immune complexes ...[more]

PMID: 29149303

Similar Datasets

Project description:BackgroundLymphatic filariasis (LF) is a neglected tropical disease and a major cause of chronic disability. Improved diagnostic tests are needed because of long-term persistence of anti-filarial antibodies or circulating filarial antigenemia after treatments that clear microfilaremia. Here, we assess changes in levels of antibodies to the recombinant filarial antigens Wb-Bhp-1, Wb123, and Bm14 after anti-filarial treatment.Methodology/principal findingsIgG4 antibodies to recombinant filarial antigens were assessed by ELISA. We tested serial plasma samples from a clinical trial in Papua New Guinea. Before treatment, 90%, 71% and 99% of participants had antibodies to Wb-Bhp-1, Wb123, and Bm14, respectively. Antibodies to Wb-Bhp-1 and Wb123, but not Bm14, were significantly higher in participants with persistent microfilaremia 24 months after treatment. Antibodies to all three antigens declined significantly by 60 months after treatment with ivermectin, diethylcarbamazine and albendazole despite circulating filarial antigen in 76% of participants. By 60 months follow up, antibodies to Wb-Bhp-1, Wb123, and Bm14 were detected in 17%, 7% and 90% of participants, respectively. Antibodies to Wb-Bhp-1 also declined more rapidly after treatment than antibodies to Bm14 in samples from a clinical trial conducted in Sri Lanka. We also tested archived serum samples from people living in filariasis-endemic communities in Egypt with different infection profiles. Antibodies to Wb-Bhp-1 were detected in 73% of microfilaremic people, 53% of amicrofilaremic people with circulating filarial antigen, and 17.5% of endemic individuals without microfilaria or circulating filarial antigen. Tests performed with legacy samples from India showed that few people with filarial lymphedema had antibodies to these recombinant antigens.ConclusionsAntibodies to Wb-Bhp-1 and Wb123 are more closely correlated with persistent microfilaremia than circulating filarial antigenemia or antibodies to Bm14, and they clear more rapidly after anti-filarial treatment. Additional studies are needed to assess the value of Wb-Bhp-1 serology as a tool for determining the success of LF elimination efforts.

Project description:BackgroundSensitive diagnostic tools that signal lymphatic filariasis (LF) transmission are needed to monitor the progress of LF elimination programs. Anti-filarial antibody (Ab) markers could be more sensitive than antigen (Ag) point-of-care tests for monitoring LF transmission in some settings. This study aimed to investigate the sensitivity of anti-filarial Abs for detecting signals of LF transmission in Samoa by i) investigating the sensitivity and specificity of Ab to identify Ag-positives; ii) estimating the average number needed to test (NNTestav) to identify LF-seropositives (seropositive for Ag and/or any Ab), and iii) compare the efficiency of the different serological indicators by target age group and sampling design.MethodsA community-based serological survey of participants aged ≥5 years was conducted 1.5-3.5 months following the first round of triple-drug mass drug administration in Samoa in 2018, covering 35 primary sampling units (PSUs) (30 randomly selected and five purposively selected 'suspected hotspots'). Ag-positivity was detected using Alere Filariasis Test Strips, and Ab-seropositivity (Bm14, Wb123, Bm33 Abs) were measured using multiplex bead assays. Seroprevalence was adjusted for study design and standardised for age and gender. NNTestav was calculated using the formula 1/p, where p was the adjusted seroprevalence for each subgroup.ResultsOf 3795 participants (mean age: 20.7; 51.2% female), 1892 (49.9%) were LF-seropositive. If Ag alone was used to identify LF-seropositives, only 5% (117/1892) would be identified. Of the three Ab seromarkers, Bm14 Ab had the highest area under the Receiver-Operating Characteristic Curve ([ROC]=0.88) to classify participants as Ag-positive, followed by Wb123 Ab (ROC=0.83) and Bm33 Ab (ROC=0.76). Participants aged ≥10 years had lower NNTestav compared to participants aged 5-9 years for all seromarkers. NNTestav was lower in purposively versus randomly selected PSUs.ConclusionsAll Ab seromarkers had high ROC values to classify patients as Ag-positive and may be useful tools for LF surveillance in some settings. However, further research is required to fully understand how best Ab serosurveillance can be incorporated into LF elimination programmes.

Dataset Information

Changes in Cytokine, Filarial Antigen, and DNA Levels Associated With Adverse Events Following Treatment of Lymphatic Filariasis.

Background

Methods

Results

Conclusions

Publications

Changes in Cytokine, Filarial Antigen, and DNA Levels Associated With Adverse Events Following Treatment of Lymphatic Filariasis.

Similar Datasets

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