Antigens and their diagnostic performance for Canine Visceral Leishmaniasis: A critical review

Castro, Raissa Barbosa de; Moraes, João Victor Badaró de; Bressan, Gustavo Costa; Vasconcellos, Raphael de Souza; Silva-Júnior, Abelardo; Fietto, Juliana Lopes Rangel

doi:10.1016/j.vetpar.2021.109638

Cited by 2 publications

(2 citation statements)

References 65 publications

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“…The current recommendation for detecting CVL in Brazil is to first screen the sample with a DPP ® CVL test based on rK28 antigen followed by confirmation through crude antigenbased ELISA (Souza et al, 2019). A recent review found that soluble antigen, or SLA, was employed in 53.8% of publications on antigenbased CVL diagnosis between 2016 and 2021 (Barbosa de Castro et al, 2022). In a study, L. infantum crude antigen in an agglutination test showed 100% sensitivity for symptomatic VL dogs as compared to 32.4% and 52.9% with rKE16 and rA2 (Farahmand et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Development of Immunological Assays Based on Leishmania donovani Antigen for Diagnosis of Canine Visceral Leishmaniasis and Their Multicenter Evaluation in Brazil and Italy

Ejazi

Saha

Bhattacharyya

et al. 2022

Front. Cell. Infect. Microbiol.

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Canine visceral leishmaniasis (CVL) due to Leishmania infantum infection is a zoonotic disease prevalent in the areas of South America and the Mediterranean. Infected dogs as reservoirs can contribute to disease transmission and can be a scourge to public health. Therefore, early diagnosis of infected dogs may play a pivotal role in circumscribing disease progression. Invasive tissue aspiration and insufficient serological methods impair a single assay for prompt CVL diagnosis. In the present study, we aimed to evaluate the potential of Leishmania donovani isolated membrane protein, LAg, for the diagnosis of CVL through immunological assays. Initially, enzyme-linked immunosorbent assay was done with Brazilian dog sera to evaluate the performance of LAg in diagnosing CVL and found sensitivity and specificity of 92.50% and 95%, respectively. The study further confirmed the diagnostic efficacy of LAg in a dipstick format. The dipstick test of canine sera from three centers in Brazil and one center in Italy collectively showed sensitivity values in the range of 53.33% to 100% in recognizing symptomatic dogs and specificity values between 75% and 100% to rule out healthy dogs. Moreover, a rapid immunochromatographic test was developed and optimized using LAg. This test was able to identify 94.73% of CVL of Brazilian origin with specificity of 97.29%. The current results highlight the reactive potential of the L. donovani antigen, LAg, for L. infantum CVL diagnosis and support our previous findings, which suggest the utility of LAg for the diagnosis of both L. donovani and L. infantum human VL in a variety of endemic regions. LAg as a diagnostic candidate may be employed to identify comprehensive CVL cases in epidemiological areas.

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Section: Discussionmentioning

confidence: 99%

Development of Immunological Assays Based on Leishmania donovani Antigen for Diagnosis of Canine Visceral Leishmaniasis and Their Multicenter Evaluation in Brazil and Italy

Ejazi

Saha

Bhattacharyya

et al. 2022

Front. Cell. Infect. Microbiol.

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“…These reservations apply to any test evaluation in which samples are classified as positive or negative based on a (less-than-perfect) reference standard and then submitted to the (also imperfect) index test(s) (cf. [10,37,38]; see also Table 1).…”

Section: Introductionmentioning

confidence: 98%

Detecting Leishmania in dogs: A hierarchical-modeling approach to investigate the performance of parasitological and qPCR-based diagnostic procedures

et al. 2022

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Background Domestic dogs are primary reservoir hosts of Leishmania infantum, the agent of visceral leishmaniasis. Detecting dog infections is central to epidemiological inference, disease prevention, and veterinary practice. Error-free diagnostic procedures, however, are lacking, and the performance of those available is difficult to measure in the absence of fail-safe “reference standards”. Here, we illustrate how a hierarchical-modeling approach can be used to formally account for false-negative and false-positive results when investigating the process of Leishmania detection in dogs. Methods/Findings We studied 294 field-sampled dogs of unknown infection status from a Leishmania-endemic region. We ran 350 parasitological tests (bone-marrow microscopy and culture) and 1,016 qPCR assays (blood, bone-marrow, and eye-swab samples with amplifiable DNA). Using replicate test results and site-occupancy models, we estimated (a) clinical sensitivity for each diagnostic procedure and (b) clinical specificity for qPCRs; parasitological tests were assumed 100% specific. Initial modeling revealed qPCR specificity < 94%; we tracked the source of this unexpected result to some qPCR plates having subtle signs of possible contamination. Using multi-model inference, we formally accounted for suspected plate contamination and estimated qPCR sensitivity at 49–53% across sample types and dog clinical conditions; qPCR specificity was high (95–96%), but fell to 81–82% for assays run in plates with suspected contamination. The sensitivity of parasitological procedures was low (~12–13%), but increased to ~33% (with substantial uncertainty) for bone-marrow culture in seriously-diseased dogs. Leishmania-infection frequency estimates (~49–50% across clinical conditions) were lower than observed (~60%). Conclusions We provide statistical estimates of key performance parameters for five diagnostic procedures used to detect Leishmania in dogs. Low clinical sensitivies likely reflect the absence of Leishmania parasites/DNA in perhaps ~50–70% of samples drawn from infected dogs. Although qPCR performance was similar across sample types, non-invasive eye-swabs were overall less likely to contain amplifiable DNA. Finally, modeling was instrumental to discovering (and formally accounting for) possible qPCR-plate contamination; even with stringent negative/blank-control scoring, ~4–5% of positive qPCRs were most likely false-positives. This work shows, in sum, how hierarchical site-occupancy models can sharpen our understanding of the problem of diagnosing host infections with hard-to-detect pathogens including Leishmania.

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Antigens and their diagnostic performance for Canine Visceral Leishmaniasis: A critical review

Cited by 2 publications

References 65 publications

Development of Immunological Assays Based on Leishmania donovani Antigen for Diagnosis of Canine Visceral Leishmaniasis and Their Multicenter Evaluation in Brazil and Italy

Development of Immunological Assays Based on Leishmania donovani Antigen for Diagnosis of Canine Visceral Leishmaniasis and Their Multicenter Evaluation in Brazil and Italy

Detecting Leishmania in dogs: A hierarchical-modeling approach to investigate the performance of parasitological and qPCR-based diagnostic procedures

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