A Four-Antigen Mixture for Rapid Assessment of Onchocerca volvulus Infection

Burbelo, Peter D.; Leahy, Hannah P.; Iadarola, Michael J.; Nutman, Thomas B.

doi:10.1371/journal.pntd.0000438

Cited by 74 publications

(56 citation statements)

References 33 publications

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“…A shortcoming of these newer assays is their inability to monitor disease progression readily. Recently, an antibody-based assay was described, which allows the parallel detection of four O. volvulus-specific antibodies, and thus discrimination among filarial infections (8). Still, humoral response-based diagnostics carry liabilities with the potential of antibody persistence even after treatments, hence confounding active/past infections.…”

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confidence: 99%

Onchocerca volvulus -neurotransmitter tyramine is a biomarker for river blindness

Globisch

Moreno

Hixon

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Onchocerciasis, also known as “river blindness”, is a neglected tropical disease infecting millions of people mainly in Africa and the Middle East but also in South America and Central America. Disease infectivity initiates from the filarial parasitic nematode Onchocerca volvulus , which is transmitted by the blackfly vector Simulium sp. carrying infectious third-stage larvae. Ivermectin has controlled transmission of microfilariae, with an African Program elimination target date of 2025. However, there is currently no point-of-care diagnostic that can distinguish the burden of infection—including active and/or past infection—and enable the elimination program to be effectively monitored. Here, we describe how liquid chromatography-MS–based urine metabolome analysis can be exploited for the identification of a unique biomarker, N -acetyltyramine- O ,β-glucuronide (NATOG), a neurotransmitter-derived secretion metabolite from O. volvulus . The regulation of this tyramine neurotransmitter was found to be linked to patient disease infection, including the controversial antibiotic doxycycline treatment that has been shown to both sterilize and kill adult female worms. Further clues to its regulation have been elucidated through biosynthetic pathway determination within the nematode and its human host. Our results demonstrate that NATOG tracks O. volvulus metabolism in both worms and humans, and thus can be considered a host-specific biomarker for onchocerciasis progression. Liquid chromatography-MS–based urine metabolome analysis discovery of NATOG not only has broad implications for a noninvasive host-specific onchocerciasis diagnostic but provides a basis for the metabolome mining of other neglected tropical diseases for the discovery of distinct biomarkers and monitoring of disease progression.

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confidence: 99%

Onchocerca volvulus -neurotransmitter tyramine is a biomarker for river blindness

Globisch

Moreno

Hixon

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…These assays based on NIE antigen have shown to be noncross-reactive in filaria-infected individuals without S. stercoralis infection in over 80 samples coming from individuals infected with other STH, filariae, or uninfected controls (21). A rapid format of the LIPS assay (called QLIPS) can be can be performed in relatively little time (less than 15 min) (5).…”

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confidence: 99%

Improved Diagnosis of Strongyloides stercoralis Using Recombinant Antigen-Based Serologies in a Community-Wide Study in Northern Argentina

Krolewiecki

Ramanathan

Fink

et al. 2010

Clin Vaccine Immunol

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The serodiagnosis of Strongyloides stercoralis infection by enzyme-linked immunosorbent assays based on crude antigen (CrAg-ELISA), while useful, has been limited by the reliance on crude parasite extracts. Newer techniques such as the luciferase immunoprecipitation system assay (LIPS), based on a 31-kDa recombinant antigen (termed NIE) from S. stercoralis and/or the recombinant antigen S. stercoralis immunoreactive antigen (SsIR), or the NIE-ELISA have shown promise in controlled settings. We compared each of these serologic assays in individuals from both regions of the world in which S. stercoralis is endemic and those in which it is not. A comprehensive stool evaluation (sedimentation concentration, Baermann concentration with charcoal cultures, agar plate, and Harada-Mori) and four different serologic techniques using CrAg-ELISA or recombinant NIE-ELISA as well as LIPS using NIE alone or in combination with a second recombinant antigen (NIE/SsIR-LIPS) were compared among individuals with parasitologically proven infection (n ‫؍‬ 251) and healthy controls from regions of the world in which the infection is nonendemic (n ‫؍‬ 11). Accuracy was calculated for each assay. The prevalence of S. stercoralis infection was 29.4% among Argentinean stool samples (n ‫؍‬ 228). Sedimentation concentration and Baermann were the most sensitive stool-based methods. NIE-LIPS showed the highest sensitivity (97.8%) and specificity (100%) of the serologic assays. The calculated negative predictive value was highest for both the NIE-LIPS and CrAg-ELISA (>97%) irrespective of disease prevalence. No cross-reactivity with soil-transmitted helminths was noted. NIE-LIPS compares favorably against the current CrAg-ELISA and stool evaluation, providing additional accuracy and ease of performance in the serodiagnosis of S. stercoralis infections irrespective of disease prevalence.

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“…Due to the liquid-phase nature of the LIPS assay and the highly linear light output of the luciferase reporter, some antibodies can be detected without serum dilution over a dynamic range of detection often spanning 7 orders of magnitude. While the LIPS test has already been shown to have a high degree of sensitivity for the detection of fungal (5), helminthic (28), filarial (10,12), and a variety of viral (3, 5-9, 11) infectious agents, its utility for the accurate evaluation of humoral responses to bacterial pathogen antigens has not been assessed. In this report, we describe the initial development and evaluation of LIPS tests for the serological diagnosis of Lyme disease.…”

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confidence: 99%

Rapid, Simple, Quantitative, and Highly Sensitive Antibody Detection for Lyme Disease

Burbelo

Issa

Ching

et al. 2010

Clin Vaccine Immunol

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There is currently a need for improved serological tests for the diagnosis and monitoring of Lyme disease, an infection caused by Borrelia burgdorferi. In the present study, we evaluated luciferase immunoprecipitation systems (LIPSs) for use for profiling of the antibody responses to a panel of B. burgdorferi proteins for the diagnosis of Lyme disease. Initially, serum samples from a cohort of patients and controls (n ‫؍‬ 46) were used for training and were profiled by the use of 15 different B. burgdorferi antigen constructs. For the patient sera, the antibody responses to several B. burgdorferi antigens, including VlsE, flagellin (FlaB), BmpA, DbpA, and DbpB, indicated that the antigens had high levels of immunoreactivity. However, the best diagnostic performance was achieved with a synthetic protein, designated VOVO, consisting of a repeated antigenic peptide sequence, VlsE-OspC-VlsE-OspC, Analysis of an independent set of serum samples (n ‫؍‬ 139) used for validation showed that the VOVO LIPS test had 98% sensitivity (95% confidence interval [CI], 93% to 100%; P < 0.0001) and 100% specificity (95% CI, 94% to 100%; P < 0.0001). Similarly, the C6 peptide enzyme-linked immunosorbent assay (ELISA) also had 98% sensitivity (95% CI, 93% to 100%; P < 0.0001) and 98% specificity (95% CI, 90% to 100%; P < 0.0001). Receiver operating characteristic analysis revealed that the rates of detection of Lyme disease by the LIPS test and the C6 ELISA were not statistically different. However, the VOVO LIPS test displayed a wide dynamic range of antibody detection spanning over 10,000-fold without the need for serum dilution. These results suggest that screening by the LIPS test with VOVO and other B. burgdorferi antigens offers an efficient quantitative approach for evaluation of the antibody responses in patients with Lyme disease.Lyme disease is caused by the spirochete Borrelia burgdorferi, which is transmitted by the bite of a deer tick (Ixodes sp.) (24,29). One of the first signs of B. burgdorferi infection is erythema migrans (EM), a skin lesion that appears within a few days at the site of the bite. Subsequently, the spirochetes can disseminate into the bloodstream and then to various target tissues and cause neurological, cardiac, and rheumatological complications (24, 29). Some individuals develop post-Lyme disease syndrome (PLDS) and have lingering symptoms, such as fatigue, musculoskeletal pain, and cognitive impairment (22,24,29).Currently, the Centers for Diseases Control and Prevention (CDC) recommends the use of a two-tier approach for serological testing for Lyme disease (1). The two-tier approach includes an initial enzyme immunoassay or immunofluorescence assay, followed by Western blotting for positive or borderline samples. The limitations of the two-tier testing approach include a low sensitivity in the very early stages of the B. burgdorferi infection, subjectivity in the interpretation of the Western blot bands, and the significant amount of time and the significant cost for the process. Moreover, curre...

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A Four-Antigen Mixture for Rapid Assessment of Onchocerca volvulus Infection

Cited by 74 publications

References 33 publications

Onchocerca volvulus -neurotransmitter tyramine is a biomarker for river blindness

Onchocerca volvulus -neurotransmitter tyramine is a biomarker for river blindness

Improved Diagnosis of Strongyloides stercoralis Using Recombinant Antigen-Based Serologies in a Community-Wide Study in Northern Argentina

Rapid, Simple, Quantitative, and Highly Sensitive Antibody Detection for Lyme Disease

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