Advances toward Diagnostic Tools for Managing Zoonotic Visceral Leishmaniasis

Duthie, Malcolm S.; Lison, Aurore; Courtenay, Orin

doi:10.1016/j.pt.2018.07.012

Cited by 32 publications

(34 citation statements)

References 96 publications

(100 reference statements)

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“…Obviously, the emergence of a superspreader is also regulated by other variables, such as immunosuppression and concomitant infections. This phenomenon has already been described in numerous parasitic diseases, including Leishmania infantum (Duthie et al, 2018).…”

Section: T Cruzi and Its Successful Transmission Strategy In Naturementioning

confidence: 55%

Landmarks of the Knowledge and Trypanosoma cruzi Biology in the Wild Environment

Jansen

Xavier

Roque

2020

Front. Cell. Infect. Microbiol.

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Trypanosomatids are ancient parasitic eukaryotes that still maintain prokaryotic characteristics. Trypanosoma cruzi, a primarily wild mammal parasite, infected humans already long before European colonization of the Americas. T. cruzi heterogeneity remains an unsolved question, and until now, it has still not been possible to associate T. cruzi genotypes with any biological or epidemiological feature. One of the first biochemical attempts to cluster the T. cruzi subpopulations recognized three main subpopulations (zymodemes) that have been associated with the transmission cycles in the wild (Z1; Z3) and in the domestic environment (Z2). The description of wild mammal species harboring Z2 two decades later challenged this assemblage attempt. Currently, the genotypes of T. cruzi are assembled in seven discrete typing units (DTUs). The biology of T. cruzi still shows novelties such as the description of epimastigotes multiplying and differentiating to metacyclic trypomastigotes in the lumen of the scent glands of Didelphis spp. and the capacity of the true meiosis in parallel to clonal reproduction. The study of the transmission cycle among wild animals has broken paradigms and raised new questions: (i) the interaction of the T. cruzi DTUs with each of its mammalian host species displays peculiarities; (ii) the impact of mixed genotypes and species on the transmissibility of one or another species or on pathogenesis is still unknown; (iii) independent T. cruzi transmission cycles may occur in the same forest fragment; (iv) the capacity to act as a reservoir depends on the peculiarities of the host species and the parasite genotype; and (v) faunistic composition is a defining trait of the T. cruzi transmission cycle profile. The development of models of environmental variables that determine the spatial distribution of the elements that make up T. cruzi transmission by spatial analysis, followed by map algebra and networking, are the next steps toward interpreting and dealing with the new profile of Chagas disease with its many peculiarities. There is no way to solve this neglected disease once and for all if not through a multidisciplinary look that takes into account all kinds of human and animal activities in parallel to environmental variations.

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Section: T Cruzi and Its Successful Transmission Strategy In Naturementioning

confidence: 55%

Landmarks of the Knowledge and Trypanosoma cruzi Biology in the Wild Environment

Jansen

Xavier

Roque

2020

Front. Cell. Infect. Microbiol.

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“…That occurred despite the fact that the three biomarkers are highly conserved between L. infantum and L. donovani. However, as discussed earlier, these results could be explained on the grounds of the known different serological, pathological, and clinical manifestations that exist between the VLs that are caused by these two different species of parasites (31,32,(34)(35)(36)(37)(38)(39).…”

Section: Figmentioning

confidence: 94%

Development of a Multiplexed Assay for Detection of Leishmania donovani and Leishmania infantum Protein Biomarkers in Urine Samples of Patients with Visceral Leishmaniasis

Abeijón¹,

Alves

Monnerat

et al. 2019

J Clin Microbiol

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Visceral leishmaniasis (VL) is a serious and fatal disease caused by the parasites Leishmania infantum and Leishmania donovani. The gold standard diagnostic test for VL is the demonstration of parasites or their DNA in spleen, lymph node, or bone marrow aspirates. Serological tests exist but cannot distinguish active VL from either prior exposure to the parasites or previously treated VL disease. Using mass spectroscopy, we have previously identified three L. infantum protein biomarkers (Li-isd1, Li-txn1, and Li-ntf2) in the urine of VL patients and developed a sensitive and specific urine-based antigen detection assay for the diagnosis of VL that occurs in Brazil (where VL is caused by L. infantum). However, unpublished observations from our laboratory at DetectoGen showed that these biomarkers were detected in only 55% to 60% of VL patients from India and Kenya, where the disease is caused by L. donovani. Here, we report the discovery and characterization of two new biomarkers of L. donovani (Ld-mao1 and Ld-ppi1) present in the urine of VL patients from these two countries. Capture enzyme-linked immunosorbent assays using specific rabbit IgG and chicken IgY were developed, and the assays had sensitivities of 44.4% and 28.8% for the detection of Ld-mao1 and Ld-ppi1, respectively. In contrast, a multiplexed assay designed to simultaneously detect all five leishmanial biomarkers markedly increased the assay sensitivity to 82.2%. These results validate the utility of leishmanial protein biomarkers found in the urine of VL patients as powerful tools for the development of an accurate diagnostic test for this disease.

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“…Variation in infection 281 estimates is expected as ultimately their precision depends on the type of diagnostic test used 282 (e.g. molecular vs. immunological), diagnostic test sensitivity and specificity, the choice of 283 clinical sample, and the stage of infection progression [17,19,20,37]. Thus, for example, as dogs 284 acquire parasitological infection prior to detection of serum containing anti-Leishmania specific 285 antibodies (seroconversion), seroprevalence data may underestimate true infection rates.…”

Section: Sensitivity Of L Infantum Infection To Biological Parametermentioning

confidence: 99%

“…In terms of canine VL, serological 34 studies undertaken in endemic areas of Brazil have found prevalence of L. infantum infection 35 to range from 25% [16] to more than 70% [17][18][19][20] depending on the diagnostic sample and 36 test employed. A consequence of the burden of L. infantum infection in the canine reservoir 37 is that Brazil has seen a steady rise in the number of human VL cases throughout the last 30 38 years [5,21]. A reported 3,500 human VL cases occur in the country per year, 90% of all VL 39 cases reported in the Americas [1,3], with the actual incidence (allowing for under-reporting) 40 estimated annually to be between 4,200 and 6,300 [1].…”

mentioning

confidence: 99%

Spatio-temporal modelling ofLeishmania infantuminfection among domestic dogs: a simulation study and sensitivity analysis applied to rural Brazil

Buckingham-Jeffery

Hill

Datta

et al. 2018

Preprint

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Background: The parasite Leishmania infantum causes zoonotic visceral leishmaniasis (VL), a potentially fatal vector-borne disease of canids and humans. Zoonotic VL poses a significant risk to public health, with regions of Latin America being particularly afflicted by the disease.Leishmania infantum parasites are transmitted between hosts during blood feeding by infected female phlebotomine sand flies. With a principal reservoir host of L. infantum being domestic dogs, limiting prevalence in this reservoir may result in a reduced risk of infection for the human population. To this end, a primary focus of research efforts has been to understand disease transmission dynamics among dogs. One way this can be achieved is through the use of mathematical models. Methods:We have developed a stochastic, spatial, individual-based mechanistic model of L. infantum transmission in domestic dogs. The model framework was applied to a rural Brazilian village setting with parameter values informed by fieldwork and laboratory data. To ensure household and sand fly populations were realistic, we statistically fit distributions for these entities to existing survey data. To identify the model parameters of highest importance, we performed a stochastic parameter sensitivity analysis of the prevalence of infection among dogs to the model parameters. Results:We computed parametric distributions for the number of humans and animals per household and a non-parametric temporal profile for sand fly abundance. The stochastic parameter sensitivity analysis determined prevalence of L. infantum infection in dogs to be most strongly affected by the sand fly associated parameters and the proportion of immigrant dogs already infected with L. infantum parasites.Conclusions: Establishing the model parameters with the highest sensitivity of average L. infantum infection prevalence in dogs to their variation helps motivate future data collection efforts focusing on these elements. Moreover, the proposed mechanistic modelling framework provides a foundation that can be expanded to explore spatial patterns of zoonotic VL in humans and to assess spatially targeted interventions.

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Advances toward Diagnostic Tools for Managing Zoonotic Visceral Leishmaniasis

Cited by 32 publications

References 96 publications

Landmarks of the Knowledge and Trypanosoma cruzi Biology in the Wild Environment

Landmarks of the Knowledge and Trypanosoma cruzi Biology in the Wild Environment

Development of a Multiplexed Assay for Detection of Leishmania donovani and Leishmania infantum Protein Biomarkers in Urine Samples of Patients with Visceral Leishmaniasis

Spatio-temporal modelling ofLeishmania infantuminfection among domestic dogs: a simulation study and sensitivity analysis applied to rural Brazil

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