A Recombinant Positive Control for Serology Diagnostic Tests Supporting Elimination of Onchocerca volvulus

Golden, Allison; Stevens, Eric; Yokobe, Lindsay; Faulx, Dunia; Kalnoky, Michael; Peck, Roger; Valdez, Melissa; Steel, Cathy; Karabou, Potochoziou K.; Banla, M.; Soboslay, Peter T.; Adade, Kangi; Tekle, Afework Hailemariam; Cama, Vitaliano; Fischer, Peter; Nutman, Thomas B.; Unnasch, Thomas R.; Santos, Tala de los; Domingo, Gonzalo J.

doi:10.1371/journal.pntd.0004292

Cited by 27 publications

(29 citation statements)

References 29 publications

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“…The studies were performed by staff members of the Togo National Program for Onchocerciasis (PNLO) and the Laboratory for Onchocerciasis Research (LRO). For each study, the staff received a two-day training course for performing study procedures including appropriate consent, data management, and utilizing the dried-down recombinant positive control [ 30 ]. In addition, a research team member was present for the first several hundred study participants to monitor test use and to provide ongoing support.…”

Section: Methodsmentioning

confidence: 99%

“…The solution was mixed gently before use in ELISA. For Ov16 ELISA, 100 μl of 5 μg/ml Ov16 antigen diluted in PBS, pH 7.4 (Sigma Chemical Company, St. Louis, MO, USA) was added to plate wells, Immulon 2HB (Fisher Scientific, Pittsburgh, PA, USA) [ 30 ]. For the glutathione-S-transferase (GST) ELISA, 100 μl of 2 μg/ml GST protein (Thermo Fisher, Waltham, MA, USA) was added to plate wells.…”

Section: Methodsmentioning

confidence: 99%

“…The anti-Ov16 IgG4 assay is transferable to the nitrocellulose rapid diagnostic test (RDT) platform [ 27 – 29 ] and is now commercially available (Alere SD BIOLINE Onchocerciasis IgG4 Rapid Test, Suwon, Republic of Korea). The availability of the assay on a point-of-care RDT platform and the development of reagents to facilitate in-country training and support quality assurance greatly enhance the operational utility of the assay for surveillance activities post-MDA as well as possibly for monitoring progression toward elimination and mapping purposes [ 30 ].…”

Section: Introductionmentioning

confidence: 99%

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Analysis of age-dependent trends in Ov16 IgG4 seroprevalence to onchocerciasis

et al. 2016

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BackgroundDiagnostics provide a means to measure progress toward disease elimination. Many countries in Africa are approaching elimination of onchocerciasis after successful implementation of mass drug administration programs as well as vector control. An understanding of how markers for infection such as skin snip microfilaria and Onchocerca volvulus-specific seroconversion perform in near-elimination settings informs how to best use these markers.MethodsAll-age participants from 35 villages in Togo were surveyed in 2013 and 2014 for skin snip Onchocerca volvulus microfilaria and IgG4 antibody response by enzyme-linked immunosorbent assay (ELISA) to the Onchocerca volvulus-specific antigen Ov16. A Gaussian mixture model applying the expectation-maximization (EM) algorithm was used to determine seropositivity from Ov16 ELISA data. For a subset of participants (n = 434), polymerase chain reaction (PCR) was performed on the skin snips taken during surveillance.ResultsWithin the 2,005 participants for which there was Ov16 ELISA data, O. volvulus microfilaremia prevalence and Ov16 seroprevalence were, 2.5 and 19.7 %, respectively, in the total population, and 1.6 and 3.6 % in children under 11. In the subset of 434 specimens for which ELISA, PCR, and microscopy data were generated, it was found that in children under 11 years of age, the anti-Ov16 IgG4 antibody response demonstrate a sensitivity and specificity of 80 and 97 %, respectively, against active infections as determined by combined PCR and microscopy on skin snips. Further analysis was performed in 34 of the 35 villages surveyed. These villages were stratified by all-age seroprevalence into three clusters: < 15 %; 15–20 %; and > 20 %. Age-dependence of seroprevalence for each cluster was best reflected by a two-phase force-of-infection (FOI) catalytic model. In all clusters, the lower of the two phases of FOI was associated with a younger age group, as reflected by the seroconversion rates for each phase. The age at which transition from lower to higher seroconversion, between the two phases of FOI, was found to be highest (older) for the cluster of villages with < 15 % seroprevalence and lowest (younger) for the cluster with the highest all-age seroprevalence.ConclusionsThe anti-Ov16 IgG4 antibody response is an accurate marker for active infection in children under 11 years of age in this population. Applying Ov16 surveillance to a broader age range provides additional valuable information for understanding progression toward elimination and can inform where targeted augmented interventions may be needed. Clustering of villages by all-age sero-surveillance allowed application of a biphasic FOI model to differentiate seroconversion rates for different age groups within the village cluster categories.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-016-1623-1) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Analysis of age-dependent trends in Ov16 IgG4 seroprevalence to onchocerciasis

et al. 2016

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“…Currently, there is no standardized commercially available Ov16 ELISA so variations in protocols and procedures exist across labs. [ 15 , 16 ] In 2014, a field deployable, rapid diagnostic tool that could be more easily integrated into current onchocerciases surveillance programs in endemic countries was developed and made commercially available (SD BIOLINE Onchocerciasis IgG4 rapid test, referred to here as Ov16 rapid test). [ 17 , 18 ] Performance of the Ov16 rapid test continues to be evaluated in the field and current global research priorities focus on operational and implementation research to demonstrate utility and increase access of the Ov16 rapid test, particularly in low prevalence settings which have undergone multiple rounds of MDA.…”

Section: Introductionmentioning

confidence: 99%

Feasibility of utilizing the SD BIOLINE Onchocerciasis IgG4 rapid test in onchocerciasis surveillance in Senegal

et al. 2017

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As effective onchocerciasis control efforts in Africa transition to elimination efforts, different diagnostic tools are required to support country programs. Senegal, with its long standing, successful control program, is transitioning to using the SD BIOLINE Onchocerciasis IgG4 (Ov16) rapid test over traditional skin snip microscopy. The aim of this study is to demonstrate the feasibility of integrating the Ov16 rapid test into onchocerciasis surveillance activities in Senegal, based on the following attributes of acceptability, usability, and cost. A cross-sectional study was conducted in 13 villages in southeastern Senegal in May 2016. Individuals 5 years and older were invited to participate in a demographic questionnaire, an Ov16 rapid test, a skin snip biopsy, and an acceptability interview. Rapid test technicians were interviewed and a costing analysis was conducted. Of 1,173 participants, 1,169 (99.7%) agreed to the rapid test while 383 (32.7%) agreed to skin snip microscopy. The sero-positivity rate of the rapid test among those tested was 2.6% with zero positives 10 years and younger. None of the 383 skin snips were positive for Ov microfilaria. Community members appreciated that the rapid test was performed quickly, was not painful, and provided reliable results. The total costs for this surveillance activity was $22,272.83, with a cost per test conducted at $3.14 for rapid test, $7.58 for skin snip microscopy, and $13.43 for shared costs. If no participants had refused skin snip microscopy, the total cost per method with shared costs would have been around $16 per person tested. In this area with low onchocerciasis sero-positivity, there was high acceptability and perceived value of the rapid test by community members and technicians. This study provides evidence of the feasibility of implementing the Ov16 rapid test in Senegal and may be informative to other country programs transitioning to Ov16 serologic tools.

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“…Traditionally, diagnosis of onchocerciasis relied on positivity for microfilariae from skin snips [6], PCR for the interspersed O-150 repeat [7] or IgG4 responses to Ov16 [8-12]. Recent modeling studies indicate the usefulness of Ov16 seropositivity in conjunction with skin snip results for MDA and surveillance programs for onchocerciasis [13].…”

Section: Introductionmentioning

confidence: 99%

Metabolite profiling of infection-associated metabolic markers of onchocerciasis

Bennuru

Lustigman

Abraham

et al. 2017

Molecular and Biochemical Parasitology

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The global efforts for onchocerciasis elimination may require additional tools (safe micro and macrofilaricidal drugs, vaccines and biomarkers) as elimination efforts move toward the “end game”. Efforts toward the identification of suitable biomarkers have focused on specific protein(s) and/or nucleic acids, but metabolites present an alternative option as they have limited half-lives and are the result of combinatorial effects. In comparison to previously used methodology of LCMS for metabolomic approaches, we used a non-targeted capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS) to analyze the serum metabolic profiles of Ov-infected and - uninfected individuals (n=20). We identified 286 known metabolites (167 in the cation mode and 119 in the anion mode). In addition, putative metabolites were identified based on KEGG (51), HMDB (37) and HMT (6) databases. One hundred ten of these putative metabolites were quantified based on peak areas of internal standards and their ability to be mapped to known pathways (primary-, carbon-, lipid-, amino acid-, nucleotide and coenzyme-metabolism). Multivariate analysis demonstrated clustering and segregation of some of these metabolites to either the infected or control groups. The levels of serotonin, hypoxanthine, pipecolic acid and inosine were significantly elevated in those with onchocerciasis, whereas the levels of glycerophosphocholine, choline and adenine were significantly lower. This non-targeted metabolomic approach provides a global view of the metabolic variations that occur during Ov infection and thus allow the discovery of key metabolites (and associated pathways) that may serve as useful biomarkers in human onchocerciasis.

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A Recombinant Positive Control for Serology Diagnostic Tests Supporting Elimination of Onchocerca volvulus

Cited by 27 publications

References 29 publications

Analysis of age-dependent trends in Ov16 IgG4 seroprevalence to onchocerciasis

Analysis of age-dependent trends in Ov16 IgG4 seroprevalence to onchocerciasis

Feasibility of utilizing the SD BIOLINE Onchocerciasis IgG4 rapid test in onchocerciasis surveillance in Senegal

Metabolite profiling of infection-associated metabolic markers of onchocerciasis

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