Non-Invasive In Vivo Study of the Trypanosoma vivax Infectious Process Consolidates the Brain Commitment in Late Infections

Trypanosoma vivax, one of the leading parasites responsible for Animal African Trypanosomosis (Nagana), is generally cyclically transmitted by Glossina spp. but in areas devoid of the tsetse flies in Africa or in Latin American countries is mechanically transmitted across vertebrate hosts by other haematophagous insects, including tabanids. We followed on from our recent studies on the maintenance of this parasite in vivo and in vitro, and its genetic manipulation, by constructing a West African IL1392 T. vivax strain that stably expresses firefly luciferase and is fully virulent for immunocompetent mice. We report here on a study where murine infection with this strain was monitored in vivo using a non-invasive method. Study findings fully support the use of this strain in the assessment of parasite dynamics in vivo since a strong correlation was found between whole body light emission measured over the course of the infection and parasitemia determined microscopically. In addition, parasitemia and survival rates were very similar for mice infected by the intraperitoneal and sub-cutaneous routes, except for a longer prepatent period following sub-cutaneous inoculation with the parasite. Our results clearly show that when administered by the subcutaneous route, the parasite is retained few days in the skin close to the inoculation site where it multiplies before passing into the bloodstream. Ex vivo bioluminescence analyses of organs isolated from infected mice corroborated our previous histopathological observations with parasite infiltration into spleen, liver and lungs. Finally, our study reinforces previous observations on the presence of the parasite in the central nervous system and consequently the brain commitment in the very late phases of the experimental infection.

[1]  K. Kristensson,et al.  Passage of parasites across the blood-brain barrier , 2012, Virulence.

[2]  H. Garcia,et al.  High mortality and lesions of the central nervous system in trypanosomosis by Trypanosoma vivax in Brazilian hair sheep. , 2011, Veterinary parasitology.

[3]  P. Minoprio,et al.  Genetic Engineering of Trypanosoma (Dutonella) vivax and In Vitro Differentiation under Axenic Conditions , 2011, PLoS neglected tropical diseases.

[4]  H. Garcia,et al.  Association of Trypanosoma vivax in extracellular sites with central nervous system lesions and changes in cerebrospinal fluid in experimentally infected goats , 2011, Veterinary research.

[5]  Xia Zhou,et al.  Intradermal Infections of Mice by Low Numbers of African Trypanosomes Are Controlled by Innate Resistance but Enhance Susceptibility to Reinfection , 2011, The Journal of infectious diseases.

[6]  Andrea Zelmer,et al.  Noninvasive biophotonic imaging for studies of infectious disease , 2010, FEMS microbiology reviews.

[7]  B. Hall,et al.  Trypanocidal Activity of Aziridinyl Nitrobenzamide Prodrugs , 2010, Antimicrobial Agents and Chemotherapy.

[8]  P. Minoprio,et al.  Trypanosoma vivax Infections: Pushing Ahead with Mouse Models for the Study of Nagana. I. Parasitological, Hematological and Pathological Parameters , 2010, PLoS neglected tropical diseases.

[9]  P. Minoprio,et al.  Trypanosoma vivax Infections: Pushing Ahead with Mouse Models for the Study of Nagana. II. Immunobiological Dysfunctions , 2010, PLoS neglected tropical diseases.

[10]  Joel W. Graff,et al.  In vivo imaging of transgenic Leishmania parasites in a live host. , 2010, Journal of visualized experiments : JoVE.

[11]  Robert W. Sauerwein,et al.  Visualisation and Quantitative Analysis of the Rodent Malaria Liver Stage by Real Time Imaging , 2009, PloS one.

[12]  N. Biteau,et al.  Murine Models for Trypanosoma brucei gambiense Disease Progression—From Silent to Chronic Infections and Early Brain Tropism , 2009, PLoS neglected tropical diseases.

[13]  Nathalie Boucher,et al.  Bioluminescent Imaging of Trypanosoma brucei Shows Preferential Testis Dissemination Which May Hamper Drug Efficacy in Sleeping Sickness , 2009, PLoS neglected tropical diseases.

[14]  J. S. Batista,et al.  Trypanosoma vivax nos tecidos testicular e epididimário de ovinos experimentalmente infectados , 2008 .

[15]  C. Janse,et al.  Simple and sensitive antimalarial drug screening in vitro and in vivo using transgenic luciferase expressing Plasmodium berghei parasites. , 2008, International journal for parasitology.

[16]  C. Olson,et al.  Bioluminescent imaging of Trypanosoma cruzi infection. , 2008, International journal for parasitology.

[17]  A. Crisanti,et al.  Temporal and Spatial Distribution of Toxoplasma gondii Differentiation into Bradyzoites and Tissue Cyst Formation In Vivo , 2008, Infection and Immunity.

[18]  M. Desquesnes,et al.  Trypanosoma (Duttonella) vivax: its biology, epidemiology, pathogenesis, and introduction in the New World--a review. , 2008, Memorias do Instituto Oswaldo Cruz.

[19]  G. Milon,et al.  Optimization of Topical Therapy for Leishmania major Localized Cutaneous Leishmaniasis Using a Reliable C57BL/6 Model , 2007, PLoS neglected tropical diseases.

[20]  Gary D Luker,et al.  Applications of bioluminescence imaging to the study of infectious diseases , 2007, Cellular microbiology.

[21]  K. Kristensson,et al.  Migration of African trypanosomes across the blood–brain barrier , 2007, Physiology & Behavior.

[22]  D. Sereno,et al.  Advances and perspectives in Leishmania cell based drug-screening procedures. , 2007, Parasitology international.

[23]  J. S. Batista,et al.  Trypanosomiasis by Trypanosoma vivax in cattle in the Brazilian semiarid: Description of an outbreak and lesions in the nervous system. , 2007, Veterinary parasitology.

[24]  M. Fatihu,et al.  Sequential testicular and epididymal damage in Zebu bulls experimentally infected with Trypanosoma vivax. , 2007, Veterinary parasitology.

[25]  Ashutosh,et al.  Use of Leishmania donovani Field Isolates Expressing the Luciferase Reporter Gene in In Vitro Drug Screening , 2005, Antimicrobial Agents and Chemotherapy.

[26]  Geneviève Milon,et al.  Bioluminescent Leishmania expressing luciferase for rapid and high throughput screening of drugs acting on amastigote‐harbouring macrophages and for quantitative real‐time monitoring of parasitism features in living mice , 2005, Cellular microbiology.

[27]  M. Desquesnes,et al.  Mechanical transmission of Trypanosoma vivax in cattle by the African tabanid Atylotus fuscipes. , 2004, Veterinary parasitology.

[28]  M. Desquesnes,et al.  Trypanosoma vivax: mechanical transmission in cattle by one of the most common African tabanids, Atylotus agrestis. , 2003, Experimental parasitology.

[29]  J. Remington,et al.  Animal models for Toxoplasma gondii infection. , 2001, Current protocols in immunology.

[30]  Monica F. Myers,et al.  Trypanosoma vivax – out of Africa , 2001 .

[31]  J. Hopkins,et al.  Trypanosoma congolense infection in sheep: ultrastructural changes in the skin prior to development of local skin reactions. , 1995, Veterinary parasitology.

[32]  A. Luckins,et al.  Multiplication of Trypanosoma evansi at the site of infection in skin of rabbits and cattle. , 1991, Acta tropica.

[33]  M. Otte,et al.  Transmission of South American Trypanosoma vivax by the neotropical horsefly Tabanus nebulosus. , 1991, Acta tropica.

[34]  H. Raymond Tabanus importunus, vecteur mécanique expérimental de Trypanosoma vivax en Guyane Française , 1990 .

[35]  P. Nyaga,et al.  Haemorrhagic pancarditis in cattle infected with Trypanosoma vivax. , 1990, Veterinary parasitology.

[36]  H. L. Raymond [Tabanus importunus, experimental mechanical vector of Trypanosoma vivax in French Guiana]. , 1990, Annales de parasitologie humaine et comparee.

[37]  P. Gardiner Recent studies of the biology of Trypanosoma vivax. , 1989, Advances in parasitology.

[38]  S. K. Moloo,et al.  Development of Trypanosoma congolense, T vivax and T brucei in the skin reaction induced in goats by infected Glossina morsitans centralis: a light and electron microscopical study. , 1988, Research in veterinary science.

[39]  H. Hirumi,et al.  Dose and stage dependency for the development of local skin reactions caused by Trypanosoma congolense in goats. , 1987, Acta tropica.

[40]  S. K. Moloo,et al.  Potential value of localized skin reactions (chancres) induced by Trypanosoma congolense transmitted by Glossina morsitans centralis for the analysis of metacyclic trypanosome populations , 1987, Parasite immunology.

[41]  A. J. Wilson,et al.  Trypanosoma (Duttonefla) vivax. , 1987, Parasitology today.

[42]  A. J. Wilson,et al.  Trypanosoma (Duttonella) vivax , 1987 .

[43]  T. Isoun,et al.  Further observations on the testicular pathology in Trypanosoma vivax infection of sheep and goats. , 1980, Research in veterinary science.

[44]  P. Leeflang,et al.  Studies on Trypanosoma vivax: infectivity and serial maintenance of natural bovine isolates in mice. , 1976, International journal for parasitology.

[45]  J. W. Hastings Bioluminescence: from chemical bonds to photons. , 1975, Ciba Foundation symposium.