Field Evaluation of a Coproantigen Detection Test for Fascioliasis Diagnosis and Surveillance in Human Hyperendemic Areas of Andean Countries

Valero, M. Adela; Periago, María Victoria; Pérez-Crespo, Ignacio; Angles, René; Villegas, Fidel; Aguirre, C.; Strauss, W; Espinoza, J.R.; Herrera, Patricia; Terashima, Angélica; Tamayo, Hugo; Engels, Dirk; Gabrielli, Albis Francesco; Mas‐Coma, Santiago

doi:10.1371/journal.pntd.0001812

Cited by 59 publications

(70 citation statements)

References 46 publications

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“…The MM3 coproantigen ELISA uses a monoclonal antibody to detect Fasciola excretory/secretory antigens in the stool. 11,12,25 This test has been evaluated for field diagnosis in humans showing a sensitivity of 94% and specificity between 93% and 98% depending on the parasite burden. 12 This test is able to detect Fasciola antigens in stool early in the infection and several days before eggs are detected by microscopy.…”

Section: Discussionmentioning

confidence: 99%

“…11 A version using the MM3 monoclonal antibody has been successfully used to test human fecal samples, but no commercial version is available and the potential for point-of-care use has not been tested. 12 The ideal diagnostic method should require minimal personnel training, be deployable to resource-limited settings, provide semiquantitative or quantitative results, and be highly sensitive to detect low-burden infections.…”

Section: Introductionmentioning

confidence: 99%

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Recombinase Polymerase Amplification Compared to Real-Time Polymerase Chain Reaction Test for the Detection of Fasciola hepatica in Human Stool

Cabada¹,

Malaga²,

Castellanos-González³

et al. 2016

Am J Trop Med Hyg

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is the most widely distributed trematode infection in the world. Control efforts may be hindered by the lack of diagnostic capacity especially in remote endemic areas. Polymerase chain reaction (PCR)-based methods offer high sensitivity and specificity but require expensive technology. However, the recombinase polymerase amplification (RPA) is an efficient isothermal method that eliminates the need for a thermal cycler and has a high deployment potential to resource-limited settings. We report on the characterization of RPA and PCR tests to detect infection in clinical stool samples with low egg burdens. The sensitivity of the RPA and PCR were 87% and 66%, respectively. Both tests were 100% specific showing no cross-reactivity with trematode, cestode, or nematode parasites. In addition, RPA and PCR were able to detect 47% and 26% of infections not detected by microscopy, respectively. The RPA adapted to a lateral flow platform was more sensitive than gel-based detection of the reaction products. In conclusion, the RPA is a highly sensitive and specific test to diagnose chronic infection using stool samples. The RPA lateral flow has the potential for deployment to endemic areas after further characterization.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Recombinase Polymerase Amplification Compared to Real-Time Polymerase Chain Reaction Test for the Detection of Fasciola hepatica in Human Stool

Cabada¹,

Malaga²,

Castellanos-González³

et al. 2016

Am J Trop Med Hyg

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show abstract

“…The frequent chronicity in infected subjects—the majority of whom are in the chronic phase of the disease, lasting for many years—is due to the fluke’s enormous longevity in humans (of up to 13.5 years) and due to the lack of diagnosis and treatment of patients, mainly children [2,4]. Indeed, chronicity is evidenced by recent multitest diagnostic studies, which have demonstrated that most of the children infected (from the age of five) in these endemic areas are already in the biliary or chronic phase of the disease [5], i.e., reinfection and chronicity are the norm in these areas.…”

Section: Introductionmentioning

confidence: 99%

Fasciola hepatica reinfection potentiates a mixed Th1/Th2/Th17/Treg response and correlates with the clinical phenotypes of anemia

et al. 2017

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BackgroundFascioliasis is a severe zoonotic disease of worldwide extension caused by liver flukes. In human fascioliasis hyperendemic areas, reinfection and chronicity are the norm and anemia is the main sign. Herein, the profile of the Th1/Th2/Th17/Treg expression levels is analyzed after reinfection, correlating them with their corresponding hematological biomarkers of morbidity.Methodology/Principal findingsThe experimental design reproduces the usual reinfection/chronicity conditions in human fascioliasis endemic areas and included Fasciola hepatica primo-infected Wistar rats (PI) and rats reinfected at 8 weeks (R8), and at 12 weeks (R12), and negative control rats. In a cross-sectional study, the expression of the genes associated with Th1 (Ifng, Il12a, Il12b, Nos2), Th2 (Il4, Arg1), Treg (Foxp3, Il10, Tgfb, Ebi3), and Th17 (Il17) in the spleen and thymus was analyzed. After 20 weeks of primary infection, PI did not present significant changes in the expression of those genes when compared to non-infected rats (NI), but an increase of Il4, Arg1 and Ifng mRNA in the spleen was observed in R12, suggesting the existence of an active mixed Th1/Th2 systemic immune response in reinfection. Foxp3, Il10, Tgfb and Ebi3 levels increased in the spleen in R12 when compared to NI and PI, indicating that the Treg gene expression levels are potentiated in chronic phase reinfection. Il17 gene expression levels in R12 in the spleen increased when compared to NI, PI and R8. Gene expression levels of Il10 in the thymus increased when compared to NI and PI in R12. Ifng expression levels in the thymus increased in all reinfected rats, but not in PI. The clinical phenotype was determined by the fluke burden, the rat body weight and the hemogram. Multivariate mathematical models were built to describe the Th1/Th2/Th17/Treg expression levels and the clinical phenotype. In reinfection, two phenotypic patterns were detected: i) one which includes only increased splenic Ifng expression levels but no Treg expression, correlating with severe anemia; ii) another which includes increased splenic Ifng and Treg expression levels, correlating with a less severe anemia.Conclusions/SignificanceIn animals with established F. hepatica infection a huge increase in the immune response occurs, being a mixed Th2/Treg associated gene expression together with an expression of Ifng. Interestingly, a Th17 associated gene expression is also observed. Reinfection in the chronic phase is able to activate a mixed immune response (Th1/Th2/Th17/Treg) against F. hepatica but T and B proliferation to mitogens is strongly suppressed in all infected rats vs control in the advanced chronic phase independently of reinfection The systemic immune response is different in each group, suggesting that suppression is mediated by different mechanisms in each case. Immune suppression could be due to the parasite in PI and R8 rats and the induction of suppressive cells such as Treg in R12. This is the first study to provide fundamental insight into the immune profile in fas...

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“…Moreover, it indicates current (rather than past) infection unlike antibody detection where the antibody titre may not wane after treatment. There are reports describing the coproantigen detection in trematodes such as F. hepatica [32] and C. sinensis [33]. We have reported the establishment of coproantigen detection method using recombinant Ov -CF in hamsters infected with O. viverrini [22].…”

Section: Discussionmentioning

confidence: 99%

Chicken IgY-based coproantigen capture ELISA for diagnosis of human opisthorchiasis

Teimoori

Arimatsu

Laha

et al. 2017

Parasitology International

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Diagnosis of Opisthorchis viverrini infection by conventional stool examination is increasingly difficult due to the low intensity of the infection after several rounds of control programmes in endemic regions as well as coinfections with intestinal flukes. Therefore sensitive and specific diagnostic test is needed. In this study, a coproantigen sandwich ELISA using recombinant O. viverrini cathepsin F (rOv-CF) was developed. This sandwich ELISA employing chicken IgY raised against rOv-CF in combination with rabbit IgG antibody to the somatic O. viverrini antigens showed a lower detection limit (LLD) of 70 ng native O. viverrini somatic antigens by spiking the parasite antigens into control feces. When applied to the diagnosis, the IgY-based sandwich ELISA exhibited sensitivity and specificity of 93.3% and 76.7%, respectively, in an investigation of 90 human cases positive or negative for opisthorchiasis. The positive predictive value (PPV) and negative predictive value (NPV) for this coproantigen detection were 66.7% and 95.2%, respectively. This IgY-based sandwich ELISA using parasite cathepsin F detection shows a promising immunodiagnostic alternative for human opisthorchiasis in endemic regions.

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Field Evaluation of a Coproantigen Detection Test for Fascioliasis Diagnosis and Surveillance in Human Hyperendemic Areas of Andean Countries

Cited by 59 publications

References 46 publications

Recombinase Polymerase Amplification Compared to Real-Time Polymerase Chain Reaction Test for the Detection of Fasciola hepatica in Human Stool

Recombinase Polymerase Amplification Compared to Real-Time Polymerase Chain Reaction Test for the Detection of Fasciola hepatica in Human Stool

Fasciola hepatica reinfection potentiates a mixed Th1/Th2/Th17/Treg response and correlates with the clinical phenotypes of anemia

Chicken IgY-based coproantigen capture ELISA for diagnosis of human opisthorchiasis

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