Semi-quantitative measurement of asymptomatic L. infantum infection and symptomatic visceral leishmaniasis in dogs using Dual-Path Platform® CVL

Abstract

Infection with Leishmania causes diseases with variable presentation. The most severe form is visceral leishmaniasis (VL), caused by either L. donovani or L. infantum. Despite efforts to eliminate VL, to date, molecular detection in resource-poor settings have lacked the accuracy and rapidity that would enable widespread field use and the need for accurate, sensitive assays to detect asymptomatic Leishmania infection has become apparent. The domestic dog serves as the primary reservoir host of L. infantum. Study of this reservoir population provides an opportunity to evaluate the sensitivity and specificity of diagnostics for well-defined, symptomatic, canine visceral leishmaniasis (CVL) and asymptomatic L. infantum infection. Blood samples from an L. infantum-endemic population of US hunting dogs were evaluated with Dual-Path Platform (DPP®) CVL compared to those obtained via direct detection methods (culture- and Leishmania-specific quantitative polymerase chain reaction, qPCR) and immunofluorescence anti-Leishmania antibody test (IFAT). Statistically significant correlations were found between DPP® CVL development time and clinical status, culture status, circulating DNA levels, and IFAT titer. DPP® CVL results correlated with both clinical severity of disease and serological evidence of asymptomatic L. infantum infection. By precisely documenting the minimum time required for the development of a clear positive result in DPP® CVL, this test could be used in a rapid, semi-quantitative manner for the evaluation of asymptomatic and symptomatic CVL. Our results also indicate that a similar test could be used to improve our understanding of human VL.

Validation of the Dual-path Platform chromatographic immunoassay (DPP® CVL rapid test) for the serodiagnosis of canine visceral leishmaniasis

“…Indeed, favourable results can also be found in asymptomatic animals. Recently, Larson et al (39) demonstrated that most animals, whether symptomatic or asymptomatic, tested positive in less than 3 min when the response time of the DPP ® CVL test was measured. Laurenti et al (25) detected infection of both symptomatic and asymptomatic animals in equal proportions.…”

Bayesian compartmental models and associated reproductive numbers for an infection with multiple transmission modes

“…While we use "susceptible" to be consistent with infectious disease modeling terminology, dogs in  are exposed, but have parasite levels below the limits of detection for the tests. If at least one test is positive, we classify a dog into , as these tests correlate well with infection, based on parasite culture and physical exams (Larson et al, 2017). We refer to this as "diagnostically positive."…”

Advances toward Diagnostic Tools for Managing Zoonotic Visceral Leishmaniasis

“…Compared to cell-based assays, serological antibody-detection tests, including indirect fluorescent antibody test (IFAT), direct agglutination test (DAT) and ELISA, are relatively cheap and, although generally more sensitive at detecting symptomatic than asymptomatic infections [70], their durability and practicality is considered an advantage particularly for low resource settings. Simple strategies can also render DPP CVL semi-quantitative, providing a more detailed diagnostic assessment and potentially a broader use in monitoring [71]. Truly asymptomatic infections usually revert to seronegative and/or low to moderate titers within months of infection and accurate quantification of responses is important in capturing this [72].…”