Abstract
BackgroundThe current antibody tests used for monitoring in lymphatic filariasis (LF) elimination programs suffer from poor specificity because of the considerable geographical overlap with other filarial infections such as Loa loa (Ll), Onchocerca volvulus (Ov), and Mansonella perstans (Mp).MethodsUsing bioinformatics to assemble into contigs 2048 expressed sequence tags (ESTs) from the L3 infective larvae of W. bancrofti (Wb), these were next assessed for homology to known proteins and nucleotides and to similar assemblies of L3 larval ESTs of B. malayi (Bm – n = 5068), Ov (n = 4166), and Ll (n = 3315). Nineteen potential L3- and Wb- and/or Bm-specific antigens were identified. Sixteen of the 19 antigens could be expressed as fusion proteins with Renilla luciferase (Ruc); these were used in a rapid Luciferase Immunopreciptation System (LIPS) assay.ResultsOne of the 16 expressed antigens (Wb123) was both highly immunogenic and specific for Wb. Using Wb123-based IgG and IgG4 LIPS assays on well-defined sera from normal North Americans and those infected exclusively with intestinal helminths, we could detect all of the Wb-infected individuals (from diverse geographic regions) with 100% sensitivity and 100% specificity. Using sera from exclusively Ll-infected, Ov-infected Mp-infected or Bm-infected subjects as the negative comparator, the sensitivities were between 98–100% and the specificities ranged between 84–100% (for IgG anti-Wb123) and between 98–100% (for IgG4 anti-Wb123). Blinded assessments using panels of sera from various Wb-, Bm- or non-Wb helminth-infected subjects demonstrated equally high degrees of sensitivity and specificity.SignificanceWe have identified a Wb-encoded antigen that can be used both as a rapid, high throughput tool to diagnose individual Wb infections and as a sensitive method for early detection of recrudescent infections in areas of control and for mapping new areas of Wb transmission.
Highlights
As one of the neglected tropical diseases (NTDs), lymphatic filariasis (LF) caused by the filarial parasites Wuchereria bancrofti (Wb), Brugia malayi (Bm) and Brugia timori can lead to disfiguring and disabling lymphedema and elephantiasis
Ethics statement All samples used were acquired under a number of registered protocols that were approved by the Institutional Review Board of National Institute of Allergy and Infectious Diseases (NIAID) with the majority being collected under either NCT00001230, NCT00342576
The resulting output, and Excel table with hyperlinks, was used to identify potential proteins that were specific for the lymphatic filariae Wuchereria bancrofti (Wb) and/or Brugia malayi (Bm) and that were without significant homology to the related filariae (Loa loa [Ll] and Onchocerca volvulus [Ov])
Summary
As one of the neglected tropical diseases (NTDs), lymphatic filariasis (LF) caused by the filarial parasites Wuchereria bancrofti (Wb), Brugia malayi (Bm) and Brugia timori can lead to disfiguring and disabling lymphedema and elephantiasis. Past and ongoing control measures, aimed at interrupting transmission by eliminating the reservoir of infection (through mass drug administration [MDA] wherever possible, e.g., Global Program for the Elimination of Lymphatic Filariasis [GPELF]) has led to substantial decreases in the prevalence of infection and the risk of disease [1] Despite these measures, estimates suggest that 120 million people remain infected with Wb or Bm with an additional 1 billion people being at risk in the tropics and subtropics worldwide [2]. The current antibody tests used for monitoring in lymphatic filariasis (LF) elimination programs suffer from poor specificity because of the considerable geographical overlap with other filarial infections such as Loa loa (Ll), Onchocerca volvulus (Ov), and Mansonella perstans (Mp)
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