molecular markers; anthroponotic transmission; leishmaniasis; drug resistance; epidemiology
Genes C M, de Lucio H, González V M, Sánchez-Murcia P A, Rico E, Gago F, Fasel N, Jiménez-Ruiz A (2016), A functional BH3 domain in an aquaporin from Leishmania infantum, in Cell Death Discovery
, 2, 16043-16043.
Martin R, Desponds C, Eren R O, Quadroni M, Thome M, Fasel N (2016), Caspase-mediated cleavage of raptor participates in the inactivation of mTORC1 during cell death, in Cell Death Discovery
, 2, 16024-16024.
Hartley Mary-Anne, Bourreau Eliane, Rossi Matteo, Castiglioni Patrik, Eren Remzi Onur, Prevel Florence, Couppié Pierre, Hickerson Suzanne M., Launois Pascal, Beverley Stephen M., Ronet Catherine, Fasel Nicolas (2016), Leishmaniavirus-Dependent Metastatic Leishmaniasis Is Prevented by Blocking IL-17A, in PLOS Pathogens
, 12(9), e1005852-e1005852.
Parmentier L., Cusini A., Muller N., Zangger H., Hartley M.-A., Desponds C., Castiglioni P., Dubach P., Ronet C., Beverley S. M., Fasel N. (2016), Severe Cutaneous Leishmaniasis in a Human Immunodeficiency Virus Patient Coinfected with Leishmania braziliensis and Its Endosymbiotic Virus, in American Journal of Tropical Medicine and Hygiene
, 94(4), 840-843.
Brettmann Erin A., Shaik Jahangheer S., Zangger Haroun, Lye Lon-Fye, Kuhlmann F. Matthew, Akopyants Natalia S., Oschwald Dayna M., Owens Katherine L., Hickerson Suzanne M., Ronet Catherine, Fasel Nicolas, Beverley Stephen M. (2016), Tilting the balance between RNA interference and replication eradicates Leishmania RNA virus 1 and mitigates the inflammatory response, in Proceedings of the National Academy of Sciences
, 113(43), 11998-12005.
Navas Adriana, Vargas Deninson Alejandro, Freudzon Marina, McMahon-Pratt Diane, Saravia Nancy Gore, Gómez María Adelaida (2014), Chronicity of Dermal Leishmaniasis Caused by Leishmania panamensis Is Associated with Parasite-Mediated Induction of Chemokine Gene Expression., in Infection and immunity
, 82(7), 2872-80.
Zangger Haroun, Hailu Asrat, Desponds Chantal, Lye Lon-Fye, Akopyants Natalia S., Dobson Deborah E., Ronet Catherine, Ghalib Hashim, Beverley Stephen M., Fasel Nicolas (2014), Leishmania aethiopica Field Isolates Bearing an Endosymbiontic dsRNA Virus Induce Pro-inflammatory Cytokine Response, in PLoS Neglected Tropical Diseases
, 8(4), e2836-e2836.
Fernández Olga Lucía, Diaz-Toro Yira, Ovalle Clemencia, Valderrama Liliana, Muvdi Sandra, Rodríguez Isabel, Gomez María Adelaida, Saravia Nancy Gore (2014), Miltefosine and antimonial drug susceptibility of Leishmania Viannia species and populations in regions of high transmission in Colombia., in PLoS neglected tropical diseases
, 8(5), 2871-2871.
Ives Annette, Masina Slavica, Castiglioni Patrik, Prével Florence, Revaz-Breton Mélanie, Hartley Mary-Anne, Launois Pascal, Fasel Nicolas, Ronet Catherine (2014), MyD88 and TLR9 Dependent Immune Responses Mediate Resistance to Leishmania guyanensis Infections, Irrespective of Leishmania RNA Virus Burden, in PLoS ONE
, 9(5), e96766-e96766.
Zangger Haroun, Ronet Catherine, Desponds Chantal, Kuhlmann F. Matthew, Robinson John, Hartley Mary-Anne, Prevel Florence, Castiglioni Patrik, Pratlong Francine, Bastien Patrick, Mueller Norbert, Parmentier Laurent, Gore Saravia Nancy, Beverley Stephen M., Fasel Nicolas (2013), Detection of Leishmania RNA Virus in Leishmania Parasites, in PLOS NEGLECTED TROPICAL DISEASES
, 7(1), 1.
Gómez Maria Adelaida, Navas Adriana, Márquez Ricardo, Rojas Laura Jimena, Vargas Deninson Alejandro, Blanco Victor Manuel, Koren Roni, Zilberstein Dan, Saravia Nancy Gore (2013), Leishmania panamensis infection and antimonial drugs modulate expression of macrophage drug transporters and metabolizing enzymes: impact on intracellular parasite survival., in The Journal of antimicrobial chemotherapy
Weinkopff Tiffany, Mariotto Anita, Simon Gregoire, Hauyon-La Torre Yazmin, Auderset Floriane, Schuster Steffen, Zangger Haroun, Fasel Nicolas, Barral Aldina, Tacchini-Cottier Fabienne (2013), Role of Toll-Like Receptor 9 Signaling in Experimental Leishmania braziliensis Infection, in INFECTION AND IMMUNITY
, 81(5), 1575-1584.
Hartley M. -A., Kohl K., Ronet C., Fasel N. (2013), The therapeutic potential of immune cross-talk in leishmaniasis, in CLINICAL MICROBIOLOGY AND INFECTION
, 19(2), 119-130.
Hartley Mary-Anne, Ronet Catherine, Fasel Nicolas (2012), Backseat drivers: the hidden influence of microbial viruses on disease., in Current opinion in microbiology
, 15(4), 538-45.
Hartley Mary-Anne, Ronet Catherine, Zangger Haroun, Beverley Stephen M, Fasel Nicolas (2012), Leishmania RNA virus: when the host pays the toll., in Frontiers in cellular and infection microbiology
, 2, 99-99.
Ronet Catherine, Beverley Stephen M, Fasel Nicolas (2011), Muco-cutaneous leishmaniasis in the New World: the ultimate subversion., in Virulence
, 2(6), 547-52.
Ronet Catherine (2011), Un virus, hôte indésirable de L. guyanensis, détermine la gravité de la forme mucocutanée, in Médecine/Sciences
, 27(11), 924-926.
Tens of thousands of cases of dermal leishmaniasis occur each year in Colombia. Transmission has expanded into the domestic setting of rural communities and periphery of urban centers, where children, women and older adults are most affected. The phenomenon of domestic transmission is common to endemic areas throughout Central and South America and its impact widespread. Control of dermal is largely limited to passive case detection and treatment in health facilities far from rural settlements. In the domestic setting of transmission many cases go undetected and without treatment because of the economic and logistical constraints of leaving homes and crops unattended and travelling with children to urban centers for diagnosis and the 20 day parenteral treatment. Clinical follow-up to determine whether treatment was successful is seldom possible for similar reasons. Available data indicate that treatment failure is frequent and multifactorial. Loss of susceptibility to antimonial drugs has been shown to be a contributing factor and higher rates of elimination in children reduces exposure to antimony to levels that can be sub-therapeutic.Molecular amplification technology has allowed the presence of Leishmania to be detected in blood and healthy skin of patients before and after treatment, and swab sampling has provided access to mucosal sites revealing parasites in apparently healthy nasal mucosa, conjunctiva and tonsils. Viability of parasites in these sites has been confirmed by amplification of Leishmania 7SLRNA transcripts. This technology and the high frequency of symptomatic and asymptomatic infections in communities experiencing transmission in and around their homes make it feasible to measure the burden of infection and to assess the participation of the infected population in domestic transmission. In addition, recent evidence supporting the participation of Leishmania virus RNA in the hyper-reactivity response associated with the development of mucosal disease and the elucidation of mechanisms of intracellular survival via resistance to oxidative stress during the initial stages of infection allow aspects of the Leishmania-host relationship that promote persistent infection and pathogenesis to be investigated in clinical strains of Leishmania.The goal of this project is to obtain the evidence base to prevent domestic transmission of dermal leishmaniasis and preserve the useful life of first line drugs. by defining the burden of Leishmania infection (symptomatic and asymptomatic) in domestically exposed populations and the role of this reservoir of human infection in transmission and the development and dissemination of drug resistance. This goal will be pursued through the concerted research of teams in Colombia and Switzerland that have a history of productive collaboration, with the following Specific Aims:1.) To determine the age-specific prevalence of parasites in blood, mucosa and dermal aspirates of the inhabitants of foci of domestic transmission of leishmaniasis. 2.) To discern the relationship between immunological evidence of infection (DTH response to intradermal leishmanin) and the presence of parasites in host tissues (blood, mucosa and healthy skin). 3.) To determine the diversity and interrelationship of Leishmania populations circulating among the inhabitants of a focus of domestic transmission. 4.) To define the drug susceptibility and virulence characteristics associated with intracellular survival and persistence in parasites isolated from lesions and extralesional tissues before and after treatment. Capacity building will target community health promoters, graduate and postdoctoral trainees and national post graduate programs biomedical science.