Monica E Staniek1, Luigi Sedda2, Tim D Gibson3, Cristian F de Souza4, Erika M Costa5, Rod J Dillon1, James G C Hamilton1. 1. Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University, Lancashire, United Kingdom. 2. Centre for Health Informatics Computation and Statistics, Lancaster Medical School, Faculty of Health and Medicine, Lancaster University, Lancashire, United Kingdom. 3. RoboScientific Ltd., Espace North, Littleport, Cambridgeshire. 4. Fiotec (Rio de Janeiro), Avenida Brasil, Manguinhos, Rio de Janeiro, Brazil. 5. Laboratório de Pesquisa em Leishmaniose, Instituto Oswaldo Cruz, Rio de Janeiro, Brazil.
Abstract
BACKGROUND: Visceral leishmaniasis (VL) in Brazil is a neglected, vector-borne, tropical parasitic disease that is responsible for several thousand human deaths every year. The transmission route involves sand flies becoming infected after feeding on infected reservoir host, mainly dogs, and then transmitting the Leishmania infantum parasites while feeding on humans. A major component of the VL control effort is the identification and euthanasia of infected dogs to remove them as a source of infection. A rapid, non-invasive, point-of-care device able to differentiate between the odours of infected and uninfected dogs may contribute towards the accurate diagnosis of canine VL. METHODOLOGY/PRINCIPAL FINDINGS: We analysed the headspace volatile chemicals from the hair of two groups of dogs collected in 2017 and 2018 using a bench-top eNose volatile organic chemical analyser. The dogs were categorised as infected or uninfected by PCR analysis of blood samples taken by venepuncture and the number of parasites per ml of blood was calculated for each dog by qPCR analysis. We demonstrated using a robust clustering analysis that the eNose data could be discriminated into infected and uninfected categories with specificity >94% and sensitivity >97%. The eNose device and data analysis were sufficiently sensitive to be able to identify infected dogs even when the Leishmania population in the circulating blood was very low. CONCLUSIONS/SIGNIFICANCE: The study illustrates the potential of the eNose to rapidly and accurately identify dogs infected with Le. infantum. Future improvements to eNose analyser sensor sensitivity, sampling methodology and portability suggest that this approach could significantly improve the diagnosis of VL infected dogs in Brazil with additional potential for effective diagnosis of VL in humans as well as for the diagnosis of other parasitic diseases.
BACKGROUND:Visceral leishmaniasis (VL) in Brazil is a neglected, vector-borne, tropical parasitic disease that is responsible for several thousand humandeaths every year. The transmission route involves sand flies becoming infected after feeding on infected reservoir host, mainly dogs, and then transmitting the Leishmania infantum parasites while feeding on humans. A major component of the VL control effort is the identification and euthanasia of infecteddogs to remove them as a source of infection. A rapid, non-invasive, point-of-care device able to differentiate between the odours of infected and uninfected dogs may contribute towards the accurate diagnosis of canineVL. METHODOLOGY/PRINCIPAL FINDINGS: We analysed the headspace volatile chemicals from the hair of two groups of dogs collected in 2017 and 2018 using a bench-top eNose volatile organic chemical analyser. The dogs were categorised as infected or uninfected by PCR analysis of blood samples taken by venepuncture and the number of parasites per ml of blood was calculated for each dog by qPCR analysis. We demonstrated using a robust clustering analysis that the eNose data could be discriminated into infected and uninfected categories with specificity >94% and sensitivity >97%. The eNose device and data analysis were sufficiently sensitive to be able to identify infecteddogs even when the Leishmania population in the circulating blood was very low. CONCLUSIONS/SIGNIFICANCE: The study illustrates the potential of the eNose to rapidly and accurately identify dogsinfected with Le. infantum. Future improvements to eNose analyser sensor sensitivity, sampling methodology and portability suggest that this approach could significantly improve the diagnosis of VL infecteddogs in Brazil with additional potential for effective diagnosis of VL in humans as well as for the diagnosis of other parasitic diseases.
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