Characterisation of the ex vivo virulence of Leishmania infantum isolates from Phlebotomus perniciosus from an outbreak of human leishmaniosis in Madrid, Spain

Domínguez‐Bernal, Gustavo; Jiménez, Maribel; Molina, Ricardo; Ordóñez-Gutiérrez, Lara; Martínez‐Rodrigo, Abel; Mas, Alicia; Cutuli, M. Teresa; Carrión, Javier

doi:10.1186/preaccept-2141223140138383

Cited by 11 publications

(15 citation statements)

References 29 publications

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“…More recently, research groups have used in vitro macrophage infection as an advantageous alternative in infectivity studies ( 17 , 18 , 28 ). Our previous experiments to standardize the in vitro conditions of macrophage and parasite co-cultures demonstrated that incubation after 3, 24, and 48 h resulted in consistent macrophage integrity and parasite growth (data not shown).…”

Section: Discussionmentioning

confidence: 99%

“…A study conducted by Cunha et al ( 17 ) characterized the biology and infectivity of viscerotropic and dermatotropic strains of L. infantum isolated from HIV+ and HIV- patients in the VL murine model, and demonstrated that in vivo and in vitro virulence are intrinsic characteristics of each strain. Another study that evaluated the ex vivo virulence of the L. infantum isolated from Phlebotomus perniciosus captured in an endemic area of Madrid, Spain, demonstrated that L. infantum strains exhibited high virulence, and were associated with cytokine production and enzymatic activities involved in the VL pathogenesis ( 18 ). Moreover, it has been shown that in vitro infection of human monocytes by Leishmania strains induced distinct immunological characteristics and the host cell's ability to control Leishmania ( 19 ).…”

Section: Introductionmentioning

confidence: 99%

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In vitro Infectivity of Strains Isolated From Dogs Naturally Infected With Leishmania infantum Present a Distinct Pathogenic Profile in Hamsters

et al. 2020

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Visceral leishmaniasis (VL) is a severe disease caused by Leishmania infantum . Dogs are the parasite's main reservoir, favoring its transmission in the urban environment. The analysis of L. infantum from infected dogs contributes to the identification of more virulent parasites, thereby supporting basic and applied studies such as vaccinal and therapeutic strategies. We proposed the in vitro and in vivo characterization of L. infantum strains from naturally infected dogs from a VL endemic area based on an infectivity and pathogenicity analysis. DH82 canine macrophages were infected in vitro with different strains for infectivity analysis, showing distinct infectivity profiles. The strains that showed greater and lesser infectivity using in vitro analyses (616 and 614, respectively) were used to infect hamsters for pathogenicity analysis. The group infected with strain 616 showed 100% survival while the group infected with strain 614 showed 50% after seven months of follow up. Furthermore, the 614 strain induced more noticeable clinicopathological changes and biochemical abnormalities in liver function, along with high inflammation and parasite load in the liver and spleen. We confirmed high variability of infectivity and pathogenicity in L. infantum strains from infected dogs. The results support the belief that screening for L. infantum infectivity using in vitro experiments is inadequate when it comes to selecting the most pathogenic strain.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

In vitro Infectivity of Strains Isolated From Dogs Naturally Infected With Leishmania infantum Present a Distinct Pathogenic Profile in Hamsters

et al. 2020

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“…Therefore, no specific tropism has been assigned to this ITS genotype. Recently, virulence of L. infantum isolates from P. perniciosus captured in the focus area was highlighted using an ex vivo model [ 59 ]. These authors showed that BOS1FL1 and POL2FL7 isolates displayed high virulence in terms of infection rates of murine macrophages and dendritic cells, cytokine production and enzymatic activities, undermining host immune defense mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Natural transmission of Leishmania infantum through experimentally infected Phlebotomus perniciosus highlights the virulence of Leishmania parasites circulating in the human visceral leishmaniasis outbreak in Madrid, Spain

Martín-Martín

Jiménez

González

et al. 2015

Vet Res

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A human leishmaniasis outbreak is occurring in the Madrid region, Spain, with the parasite and vector involved being Leishmania infantum and Phlebotomus perniciosus respectively. The aim of this study was to investigate the virulence of L. infantum isolates from the focus using a natural transmission model. Hamsters were infected by intraperitoneal inoculation (IP) or by bites of sand flies experimentally infected with L. infantum isolates obtained from P. perniciosus collected in the outbreak area (IPER/ES/2012/BOS1FL1 and IPER/ES/2012/POL2FL6) and a well characterized L. infantum strain JPCM5 (MCAN/ES/98/LLM-877). Hamster infections were monitored by clinical examination, serology, culture, parasite burden, Giemsa-stained imprints, PCR, histopathology and xenodiagnostic studies. Establishment of infection of L. infantum was achieved with the JPCM5 strain and outbreak isolates by both P. perniciosus infective bites or IP route. However, high virulence of BOS1FL1 and POL2FL6 isolates was highlighted by the clinical outcome of disease, high parasite detection in spleen and liver, high parasitic loads and positivity of Leishmania serology. Transmission by bite of POL2FL6 infected flies generated a slower progression of clinical disease than IP infection, but both groups were infective to P. perniciosus by xenodiagnosis at 2 months post-infection. Conversely, hamsters inoculated with JPCM5 were not infective to sand flies. Histopathology studies confirmed the wide spread of POL2FL6 parasites to several organs. A visceral leishmaniasis model that mimics the natural transmission in nature allowed us to highlight the high virulence of isolates that are circulating in the focus. These findings contribute to a better understanding of the outbreak epidemiology.

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“…In the Mediterranean region, and in Central and South America, the disease is zoonotic and caused by L. infantum (= L. chagasi ) where the main reservoir is dogs (11). Recently, cats and leporids have also been considered as possible alternative reservoirs of VL in certain foci in the Mediterranean region (12). Ninety percent of VL cases occur in five countries – India, Bangladesh, Nepal, Sudan, and Brazil – most often in remote regions without ready access to medical care.…”

Section: Introductionmentioning

confidence: 99%

Leishmania vaccine development: exploiting the host–vector–parasite interface

Reed

Coler

Mondal

et al. 2015

Expert Review of Vaccines

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Summary Visceral leishmaniasis (VL) is a disease transmitted by phlebotomine sand flies, fatal if untreated, and with no available human vaccine. In rodents, cellular immunity to Leishmania parasite proteins as well as salivary proteins of the sand fly is associated with protection, making them worthy targets for further exploration as vaccines. This review discusses the notion that a combination vaccine including Leishmania and vector salivary antigens may improve vaccine efficacy by targeting the parasite at its most vulnerable stage just after transmission. Furthermore, we put forward the notion that better modeling of natural transmission is needed to test efficacy of vaccines. For example, the fact that individuals living in endemic areas are exposed to sand fly bites and will mount an immune response to salivary proteins should be considered in pre-clinical and clinical evaluation of leishmaniasis vaccines. Nevertheless, despite remaining obstacles there is good reason to be optimistic that safe and effective vaccines against leishmaniasis can be developed.

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Characterisation of the ex vivo virulence of Leishmania infantum isolates from Phlebotomus perniciosus from an outbreak of human leishmaniosis in Madrid, Spain

Cited by 11 publications

References 29 publications

In vitro Infectivity of Strains Isolated From Dogs Naturally Infected With Leishmania infantum Present a Distinct Pathogenic Profile in Hamsters

In vitro Infectivity of Strains Isolated From Dogs Naturally Infected With Leishmania infantum Present a Distinct Pathogenic Profile in Hamsters

Natural transmission of Leishmania infantum through experimentally infected Phlebotomus perniciosus highlights the virulence of Leishmania parasites circulating in the human visceral leishmaniasis outbreak in Madrid, Spain

Leishmania vaccine development: exploiting the host–vector–parasite interface

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