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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">ANIMAL MODELS FOR THE STUDY OF LEISHMANIASIS
IMMUNOLOGY</title><author><name sortKey="Loria Cervera, Elsy Nalleli" sort="Loria Cervera, Elsy Nalleli" uniqKey="Loria Cervera E" first="Elsy Nalleli" last="Loría-Cervera">Elsy Nalleli Loría-Cervera</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Andrade Narvaez, Fernando Jose" sort="Andrade Narvaez, Fernando Jose" uniqKey="Andrade Narvaez F" first="Fernando José" last="Andrade-Narváez">Fernando José Andrade-Narváez</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">24553602</idno><idno type="pmc">4085833</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4085833</idno><idno type="RBID">PMC:4085833</idno><idno type="doi">10.1590/S0036-46652014000100001</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">000098</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000098</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">ANIMAL MODELS FOR THE STUDY OF LEISHMANIASIS
IMMUNOLOGY</title><author><name sortKey="Loria Cervera, Elsy Nalleli" sort="Loria Cervera, Elsy Nalleli" uniqKey="Loria Cervera E" first="Elsy Nalleli" last="Loría-Cervera">Elsy Nalleli Loría-Cervera</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Andrade Narvaez, Fernando Jose" sort="Andrade Narvaez, Fernando Jose" uniqKey="Andrade Narvaez F" first="Fernando José" last="Andrade-Narváez">Fernando José Andrade-Narváez</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author></analytic><series><title level="j">Revista do Instituto de Medicina Tropical de São Paulo</title><idno type="ISSN">0036-4665</idno><idno type="eISSN">1678-9946</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="para1">Leishmaniasis remains a major public health problem worldwide and is
classified as Category I by the TDR/WHO, mainly due to the absence of control. Many
experimental models like rodents, dogs and monkeys have been developed, each with
specific features, in order to characterize the immune response to
<italic>Leishmania</italic> species, but none reproduces the pathology observed in
human disease. Conflicting data may arise in part because different parasite strains
or species are being examined, different tissue targets (mice footpad, ear, or base
of tail) are being infected, and different numbers (“low” 1×10<sup>2</sup> and “high”
1×10<sup>6</sup>) of metacyclic promastigotes have been inoculated. Recently, new
approaches have been proposed to provide more meaningful data regarding the host
response and pathogenesis that parallels human disease. The use of sand fly saliva
and low numbers of parasites in experimental infections has led to mimic natural
transmission and find new molecules and immune mechanisms which should be considered
when designing vaccines and control strategies. Moreover, the use of wild rodents as
experimental models has been proposed as a good alternative for studying the
host-pathogen relationships and for testing candidate vaccines. To date, using
natural reservoirs to study <italic>Leishmania</italic> infection has been
challenging because immunologic reagents for use in wild rodents are lacking. This
review discusses the principal immunological findings against
<italic>Leishmania</italic> infection in different animal models highlighting the
importance of using experimental conditions similar to natural transmission and
reservoir species as experimental models to study the immunopathology of the
disease.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Afonso, Lc" uniqKey="Afonso L">LC Afonso</name></author><author><name sortKey="Scott, P" uniqKey="Scott P">P Scott</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Aguilar Torrentera, F" uniqKey="Aguilar Torrentera F">F Aguilar-Torrentera</name></author><author><name sortKey="Carlier, Y" uniqKey="Carlier Y">Y Carlier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Aguilar Torrentera, F" uniqKey="Aguilar Torrentera F">F Aguilar-Torrentera</name></author><author><name sortKey="Laman, Jd" uniqKey="Laman J">JD Laman</name></author><author><name sortKey="Van Meurs, M" uniqKey="Van Meurs M">M Van Meurs</name></author><author><name sortKey="Adorini, L" uniqKey="Adorini L">L Adorini</name></author><author><name sortKey="Muraille, E" uniqKey="Muraille E">E Muraille</name></author><author><name sortKey="Carlieri, Y" uniqKey="Carlieri Y">Y Carlieri</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Alvar, J" uniqKey="Alvar J">J Alvar</name></author><author><name sortKey="Ca Avate, C" uniqKey="Ca Avate C">C Cañavate</name></author><author><name sortKey="Molina, R" uniqKey="Molina R">R Molina</name></author><author><name sortKey="Moreno, J" uniqKey="Moreno J">J Moreno</name></author><author><name sortKey="Nieto, J" uniqKey="Nieto J">J Nieto</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Alvar, J" uniqKey="Alvar J">J Alvar</name></author><author><name sortKey="Yactayo, S" uniqKey="Yactayo S">S Yactayo</name></author><author><name sortKey="Bern, C" uniqKey="Bern C">C Bern</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Alvar, J" uniqKey="Alvar J">J Alvar</name></author><author><name sortKey="Velez, Id" uniqKey="Velez I">ID Vélez</name></author><author><name sortKey="Bern, C" uniqKey="Bern C">C Bern</name></author><author><name sortKey="Herrero, M" uniqKey="Herrero M">M Herrero</name></author><author><name sortKey="Desjeux, P" uniqKey="Desjeux P">P Desjeux</name></author><author><name sortKey="Cano, J" uniqKey="Cano J">J Cano</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Amaral, Vf" uniqKey="Amaral V">VF Amaral</name></author><author><name sortKey="Pirmez, C" uniqKey="Pirmez C">C Pirmez</name></author><author><name sortKey="Goncalves, Ajs" uniqKey="Goncalves A">AJS Gonçalves</name></author><author><name sortKey="Ferreira, V" uniqKey="Ferreira V">V Ferreira</name></author><author><name sortKey="Grimaldi, G" uniqKey="Grimaldi G">G Grimaldi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Amaral, Vf" uniqKey="Amaral V">VF Amaral</name></author><author><name sortKey="Teva, A" uniqKey="Teva A">A Teva</name></author><author><name sortKey="Porrozzi, R" uniqKey="Porrozzi R">R Porrozzi</name></author><author><name sortKey="Silva, Aj" uniqKey="Silva A">AJ Silva</name></author><author><name sortKey="Pereira, Ms" uniqKey="Pereira M">MS Pereira</name></author><author><name sortKey="Oliveira Neto, Mp" uniqKey="Oliveira Neto M">MP Oliveira-Neto</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Banerjee, R" uniqKey="Banerjee R">R Banerjee</name></author><author><name sortKey="Kumar, S" uniqKey="Kumar S">S Kumar</name></author><author><name sortKey="Sen, A" uniqKey="Sen A">A Sen</name></author><author><name sortKey="Mookerjee, A" uniqKey="Mookerjee A">A Mookerjee</name></author><author><name sortKey="Roy, S" uniqKey="Roy S">S Roy</name></author><author><name sortKey="Pal, S" uniqKey="Pal S">S Pal</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Baneth, G" uniqKey="Baneth G">G Baneth</name></author><author><name sortKey="Koutinas, Af" uniqKey="Koutinas A">AF Koutinas</name></author><author><name sortKey="Solano Gallego, L" uniqKey="Solano Gallego L">L Solano-Gallego</name></author><author><name sortKey="Bourdeau, P" uniqKey="Bourdeau P">P Bourdeau</name></author><author><name sortKey="Ferrer, L" uniqKey="Ferrer L">L Ferrer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Barral Netto, M" uniqKey="Barral Netto M">M Barral-Netto</name></author><author><name sortKey="Barral, A" uniqKey="Barral A">A Barral</name></author><author><name sortKey="Brownell, Ce" uniqKey="Brownell C">CE Brownell</name></author><author><name sortKey="Skeiky, Yaw" uniqKey="Skeiky Y">YAW Skeiky</name></author><author><name sortKey="Ellingsworth, Lr" uniqKey="Ellingsworth L">LR Ellingsworth</name></author><author><name sortKey="Twardzik, Dr" uniqKey="Twardzik D">DR Twardzik</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Beattie, L" uniqKey="Beattie L">L Beattie</name></author><author><name sortKey="Peltan, A" uniqKey="Peltan A">A Peltan</name></author><author><name sortKey="Maroof, A" uniqKey="Maroof A">A Maroof</name></author><author><name sortKey="Kirby, A" uniqKey="Kirby A">A Kirby</name></author><author><name sortKey="Brown, N" uniqKey="Brown N">N Brown</name></author><author><name sortKey="Coles, M" uniqKey="Coles M">M Coles</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Belkaid, Y" uniqKey="Belkaid Y">Y Belkaid</name></author><author><name sortKey="Kamhawi, S" uniqKey="Kamhawi S">S Kamhawi</name></author><author><name sortKey="Modi, G" uniqKey="Modi G">G Modi</name></author><author><name sortKey="Valenzuela, J" uniqKey="Valenzuela J">J Valenzuela</name></author><author><name sortKey="Noben Trauth, N" uniqKey="Noben Trauth N">N Noben-Trauth</name></author><author><name sortKey="Rowton, E" uniqKey="Rowton E">E Rowton</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bern, C" uniqKey="Bern C">C Bern</name></author><author><name sortKey="Maguire, Jh" uniqKey="Maguire J">JH Maguire</name></author><author><name sortKey="Alvar, J" uniqKey="Alvar J">J Alvar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bezerril Andrade, B" uniqKey="Bezerril Andrade B">B Bezerril Andrade</name></author><author><name sortKey="Teixeira, Cr" uniqKey="Teixeira C">CR Teixeira</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Blackwell, Jm" uniqKey="Blackwell J">JM Blackwell</name></author><author><name sortKey="Fakiola, M" uniqKey="Fakiola M">M Fakiola</name></author><author><name sortKey="Ibrahim, Me" uniqKey="Ibrahim M">ME Ibrahim</name></author><author><name sortKey="Jamieson, Se" uniqKey="Jamieson S">SE Jamieson</name></author><author><name sortKey="Jeronimo, Sb" uniqKey="Jeronimo S">SB Jeronimo</name></author><author><name sortKey="Miller, En" uniqKey="Miller E">EN Miller</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Blackwell, Jm" uniqKey="Blackwell J">JM Blackwell</name></author><author><name sortKey="Goswami, T" uniqKey="Goswami T">T Goswami</name></author><author><name sortKey="Evans, Caw" uniqKey="Evans C">CAW Evans</name></author><author><name sortKey="Sibthorpe, D" uniqKey="Sibthorpe D">D Sibthorpe</name></author><author><name sortKey="Papo, N" uniqKey="Papo N">N Papo</name></author><author><name sortKey="White, Jk" uniqKey="White J">JK White</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bogdan, C" uniqKey="Bogdan C">C Bogdan</name></author><author><name sortKey="Rollinghoff, M" uniqKey="Rollinghoff M">M Röllinghoff</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bourdoiseau, G" uniqKey="Bourdoiseau G">G Bourdoiseau</name></author><author><name sortKey="Bonnefont, C" uniqKey="Bonnefont C">C Bonnefont</name></author><author><name sortKey="Hoareau, E" uniqKey="Hoareau E">E Hoareau</name></author><author><name sortKey="Boehringer, C" uniqKey="Boehringer C">C Boehringer</name></author><author><name sortKey="Stolle, T" uniqKey="Stolle T">T Stolle</name></author><author><name sortKey="Chabanne, L" uniqKey="Chabanne L">L Chabanne</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Broderson, Jr" uniqKey="Broderson J">JR Broderson</name></author><author><name sortKey="Chapman, Wl" uniqKey="Chapman W">WL Chapman</name></author><author><name sortKey="Hanson, Wl" uniqKey="Hanson W">WL Hanson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Buxbaum, Lu" uniqKey="Buxbaum L">LU Buxbaum</name></author><author><name sortKey="Uzonna, Je" uniqKey="Uzonna J">JE Uzonna</name></author><author><name sortKey="Goldschmidt, Mh" uniqKey="Goldschmidt M">MH Goldschmidt</name></author><author><name sortKey="Scott, P" uniqKey="Scott P">P Scott</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Canto Lara, Sb" uniqKey="Canto Lara S">SB Canto-Lara</name></author><author><name sortKey="Van Wynsberghe, Nr" uniqKey="Van Wynsberghe N">NR Van Wynsberghe</name></author><author><name sortKey="Vargas Gonzalez, A" uniqKey="Vargas Gonzalez A">A Vargas-Gonzalez</name></author><author><name sortKey="Ojeda Farfan, Ff" uniqKey="Ojeda Farfan F">FF Ojeda-Farfán</name></author><author><name sortKey="Andrade Narvaez, Fj" uniqKey="Andrade Narvaez F">FJ Andrade-Narváez</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Carsillo, M" uniqKey="Carsillo M">M Carsillo</name></author><author><name sortKey="Kutala, Vk" uniqKey="Kutala V">VK Kutala</name></author><author><name sortKey="Puschel, K" uniqKey="Puschel K">K Puschel</name></author><author><name sortKey="Blaco, J" uniqKey="Blaco J">J Blaco</name></author><author><name sortKey="Kuppusamy, P" uniqKey="Kuppusamy P">P Kuppusamy</name></author><author><name sortKey="Niewiesk, S" uniqKey="Niewiesk S">S Niewiesk</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chable Santos, Jb" uniqKey="Chable Santos J">JB Chable-Santos</name></author><author><name sortKey="Van Wynsberghe, Nr" uniqKey="Van Wynsberghe N">NR Van Wynsberghe</name></author><author><name sortKey="Canto Lara, Sb" uniqKey="Canto Lara S">SB Canto-Lara</name></author><author><name sortKey="Andrade Narvaez, Fj" uniqKey="Andrade Narvaez F">FJ Andrade-Narváez</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chamizo, C" uniqKey="Chamizo C">C Chamizo</name></author><author><name sortKey="Moreno, J" uniqKey="Moreno J">J Moreno</name></author><author><name sortKey="Alvar, J" uniqKey="Alvar J">J Alvar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chang, Kp" uniqKey="Chang K">KP Chang</name></author><author><name sortKey="Dwyer, Dm" uniqKey="Dwyer D">DM Dwyer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ciaramella, P" uniqKey="Ciaramella P">P Ciaramella</name></author><author><name sortKey="Oliva, G" uniqKey="Oliva G">G Oliva</name></author><author><name sortKey="Luna, Rd" uniqKey="Luna R">RD Luna</name></author><author><name sortKey="Gradoni, L" uniqKey="Gradoni L">L Gradoni</name></author><author><name sortKey="Ambrosio, R" uniqKey="Ambrosio R">R Ambrosio</name></author><author><name sortKey="Cortese, L" uniqKey="Cortese L">L Cortese</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Cua Ake, Ma" uniqKey="Cua Ake M">MA Cua Ake</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dantas Torres, F" uniqKey="Dantas Torres F">F Dantas-Torres</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Almeida, Mc De" uniqKey="Almeida M">MC De Almeida</name></author><author><name sortKey="Vilhena, V" uniqKey="Vilhena V">V Vilhena</name></author><author><name sortKey="Barral, V" uniqKey="Barral V">V Barral</name></author><author><name sortKey="Barral Netto, M" uniqKey="Barral Netto M">M Barral-Netto</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Campos, Sn De" uniqKey="Campos S">SN De Campos</name></author><author><name sortKey="Souza Lemos, C" uniqKey="Souza Lemos C">C Souza-Lemos</name></author><author><name sortKey="Teva, A" uniqKey="Teva A">A Teva</name></author><author><name sortKey="Porrozzi, R" uniqKey="Porrozzi R">R Porrozzi</name></author><author><name sortKey="Grimaldi, G" uniqKey="Grimaldi G">G Grimaldi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lima, H De" uniqKey="Lima H">H De Lima</name></author><author><name sortKey="Guglielmo, Z De" uniqKey="Guglielmo Z">Z De Guglielmo</name></author><author><name sortKey="Rodriguez, A" uniqKey="Rodriguez A">A Rodríguez</name></author><author><name sortKey="Convit, J" uniqKey="Convit J">J Convit</name></author><author><name sortKey="Rodriguez, N" uniqKey="Rodriguez N">N Rodríguez</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dennis, Va" uniqKey="Dennis V">VA Dennis</name></author><author><name sortKey="Lujan, R" uniqKey="Lujan R">R Lujan</name></author><author><name sortKey="Chapman, Wl" uniqKey="Chapman W">WL Chapman</name></author><author><name sortKey="Hanson, Wl" uniqKey="Hanson W">WL Hanson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Desjeux, P" uniqKey="Desjeux P">P Desjeux</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Desjeux, P" uniqKey="Desjeux P">P Desjeux</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Doherty, Tm" uniqKey="Doherty T">TM Doherty</name></author><author><name sortKey="Coffman, Rl" uniqKey="Coffman R">RL Coffman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dube, A" uniqKey="Dube A">A Dube</name></author><author><name sortKey="Sharma, P" uniqKey="Sharma P">P Sharma</name></author><author><name sortKey="Srivastava, Jk" uniqKey="Srivastava J">JK Srivastava</name></author><author><name sortKey="Misra, A" uniqKey="Misra A">A Misra</name></author><author><name sortKey="Naik, S" uniqKey="Naik S">S Naik</name></author><author><name sortKey="Katiyar, Jc" uniqKey="Katiyar J">JC Katiyar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Engwerda, Cr" uniqKey="Engwerda C">CR Engwerda</name></author><author><name sortKey="Ato, M" uniqKey="Ato M">M Ato</name></author><author><name sortKey="Kaye, Pm" uniqKey="Kaye P">PM Kaye</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Espitia, Cm" uniqKey="Espitia C">CM Espitia</name></author><author><name sortKey="Zhao, W" uniqKey="Zhao W">W Zhao</name></author><author><name sortKey="Saldarriaga, O" uniqKey="Saldarriaga O">O Saldarriaga</name></author><author><name sortKey="Osorio, Y" uniqKey="Osorio Y">Y Osorio</name></author><author><name sortKey="Harrison, Lm" uniqKey="Harrison L">LM Harrison</name></author><author><name sortKey="Cappello, M" uniqKey="Cappello M">M Cappello</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fazzani, C" uniqKey="Fazzani C">C Fazzani</name></author><author><name sortKey="Guedes, Pa" uniqKey="Guedes P">PA Guedes</name></author><author><name sortKey="Sena, A" uniqKey="Sena A">A Sena</name></author><author><name sortKey="Souza, Eb" uniqKey="Souza E">EB Souza</name></author><author><name sortKey="Goto, H" uniqKey="Goto H">H Goto</name></author><author><name sortKey="Lindoso, Jal" uniqKey="Lindoso J">JAL Lindoso</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gantt, Kr" uniqKey="Gantt K">KR Gantt</name></author><author><name sortKey="Goldman, Tl" uniqKey="Goldman T">TL Goldman</name></author><author><name sortKey="Mccormick, Ml" uniqKey="Mccormick M">ML McCormick</name></author><author><name sortKey="Miller, Ma" uniqKey="Miller M">MA Miller</name></author><author><name sortKey="Jeronimo, Smb" uniqKey="Jeronimo S">SMB Jeronimo</name></author><author><name sortKey="Nascimento, Et" uniqKey="Nascimento E">ET Nascimento</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gicheru, Mm" uniqKey="Gicheru M">MM Gicheru</name></author><author><name sortKey="Olobo, Jo" uniqKey="Olobo J">JO Olobo</name></author><author><name sortKey="Kariuki, Tm" uniqKey="Kariuki T">TM Kariuki</name></author><author><name sortKey="Adhiambo, C" uniqKey="Adhiambo C">C Adhiambo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gomes, R" uniqKey="Gomes R">R Gomes</name></author><author><name sortKey="Teixeira, C" uniqKey="Teixeira C">C Teixeira</name></author><author><name sortKey="Texeira, Mj" uniqKey="Texeira M">MJ Texeira</name></author><author><name sortKey="Oliveira, F" uniqKey="Oliveira F">F Oliveira</name></author><author><name sortKey="Menezes, Mj" uniqKey="Menezes M">MJ Menezes</name></author><author><name sortKey="Silva, C" uniqKey="Silva C">C Silva</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Goto, H" uniqKey="Goto H">H Goto</name></author><author><name sortKey="Prianti, Mg" uniqKey="Prianti M">MG Prianti</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Grimaldi, G" uniqKey="Grimaldi G">G Grimaldi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Guenet, Jl" uniqKey="Guenet J">JL Guénet</name></author><author><name sortKey="Bonhomme, F" uniqKey="Bonhomme F">F Bonhomme</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gupta, S" uniqKey="Gupta S">S Gupta</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Handman, E" uniqKey="Handman E">E Handman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hommel, M" uniqKey="Hommel M">M Hommel</name></author><author><name sortKey="Jaffe, Cl" uniqKey="Jaffe C">CL Jaffe</name></author><author><name sortKey="Travi, B" uniqKey="Travi B">B Travi</name></author><author><name sortKey="Milon, G" uniqKey="Milon G">G Milon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hotez, Pj" uniqKey="Hotez P">PJ Hotez</name></author><author><name sortKey="Remme, Jh" uniqKey="Remme J">JH Remme</name></author><author><name sortKey="Buss, P" uniqKey="Buss P">P Buss</name></author><author><name sortKey="Alleyne, G" uniqKey="Alleyne G">G Alleyne</name></author><author><name sortKey="Morel, C" uniqKey="Morel C">C Morel</name></author><author><name sortKey="Breman, Jg" uniqKey="Breman J">JG Breman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hotez, Pj" uniqKey="Hotez P">PJ Hotez</name></author><author><name sortKey="Molyneux, Dh" uniqKey="Molyneux D">DH Molyneux</name></author><author><name sortKey="Fenwick, A" uniqKey="Fenwick A">A Fenwick</name></author><author><name sortKey="Ottesen, E" uniqKey="Ottesen E">E Ottesen</name></author><author><name sortKey="Ehrlich Sachs, S" uniqKey="Ehrlich Sachs S">S Ehrlich Sachs</name></author><author><name sortKey="Sachs, Jd" uniqKey="Sachs J">JD Sachs</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jones, De" uniqKey="Jones D">DE Jones</name></author><author><name sortKey="Ackermann, Mr" uniqKey="Ackermann M">MR Ackermann</name></author><author><name sortKey="Wille, U" uniqKey="Wille U">U Wille</name></author><author><name sortKey="Hunter, Ca" uniqKey="Hunter C">CA Hunter</name></author><author><name sortKey="Scott, P" uniqKey="Scott P">P Scott</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jones, De" uniqKey="Jones D">DE Jones</name></author><author><name sortKey="Buxbaum, Lu" uniqKey="Buxbaum L">LU Buxbaum</name></author><author><name sortKey="Scott, P" uniqKey="Scott P">P Scott</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kedzierski, L" uniqKey="Kedzierski L">L Kedzierski</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kenney, Rt" uniqKey="Kenney R">RT Kenney</name></author><author><name sortKey="Sacks, Dl" uniqKey="Sacks D">DL Sacks</name></author><author><name sortKey="Sypek, Jp" uniqKey="Sypek J">JP Sypek</name></author><author><name sortKey="Vilela, L" uniqKey="Vilela L">L Vilela</name></author><author><name sortKey="Gam, Aa" uniqKey="Gam A">AA Gam</name></author><author><name sortKey="Evans Davis, K" uniqKey="Evans Davis K">K Evans-Davis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kimblin, N" uniqKey="Kimblin N">N Kimblin</name></author><author><name sortKey="Peters, N" uniqKey="Peters N">N Peters</name></author><author><name sortKey="Debrabant, A" uniqKey="Debrabant A">A Debrabant</name></author><author><name sortKey="Secundino, N" uniqKey="Secundino N">N Secundino</name></author><author><name sortKey="Egen, J" uniqKey="Egen J">J Egen</name></author><author><name sortKey="Lawyer, P" uniqKey="Lawyer P">P Lawyer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kumar, R" uniqKey="Kumar R">R Kumar</name></author><author><name sortKey="Nylen, S" uniqKey="Nylen S">S Nylén</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lage, Rs" uniqKey="Lage R">RS Lage</name></author><author><name sortKey="Oliveira, Gc" uniqKey="Oliveira G">GC Oliveira</name></author><author><name sortKey="Busek, Su" uniqKey="Busek S">SU Busek</name></author><author><name sortKey="Guerra, Ll" uniqKey="Guerra L">LL Guerra</name></author><author><name sortKey="Giunchetti, Rc" uniqKey="Giunchetti R">RC Giunchetti</name></author><author><name sortKey="Correa Oliveira, R" uniqKey="Correa Oliveira R">R Corrêa-Oliveira</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lang, T" uniqKey="Lang T">T Lang</name></author><author><name sortKey="Courret, N" uniqKey="Courret N">N Courret</name></author><author><name sortKey="Colle, Jh" uniqKey="Colle J">JH Colle</name></author><author><name sortKey="Milon, G" uniqKey="Milon G">G Milon</name></author><author><name sortKey="Antoine, Jc" uniqKey="Antoine J">JC Antoine</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liew, Fy" uniqKey="Liew F">FY Liew</name></author><author><name sortKey="Wei, X" uniqKey="Wei X">X Wei</name></author><author><name sortKey="Proudfoot, L" uniqKey="Proudfoot L">L Proudfoot</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lima, Ch" uniqKey="Lima C">CH Lima</name></author><author><name sortKey="Titus, Rg" uniqKey="Titus R">RG Titus</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Loria Cervera, En" uniqKey="Loria Cervera E">EN Loría Cervera</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Loria Cervera, En" uniqKey="Loria Cervera E">EN Loría-Cervera</name></author><author><name sortKey="Sosa Bibiano, Ei" uniqKey="Sosa Bibiano E">EI Sosa-Bibiano</name></author><author><name sortKey="Villanueva Lizama, Le" uniqKey="Villanueva Lizama L">LE Villanueva-Lizama</name></author><author><name sortKey="Van Wynsberghe, Nr" uniqKey="Van Wynsberghe N">NR Van Wynsberghe</name></author><author><name sortKey="Canto Lara, Sb" uniqKey="Canto Lara S">SB Canto-Lara</name></author><author><name sortKey="Batun Cutz, Jl" uniqKey="Batun Cutz J">JL Batún-Cutz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mauel, J" uniqKey="Mauel J">J Maüel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mcmahon Pratt, D" uniqKey="Mcmahon Pratt D">D McMahon-Pratt</name></author><author><name sortKey="Alexander, J" uniqKey="Alexander J">J Alexander</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Melby, P" uniqKey="Melby P">P Melby</name></author><author><name sortKey="Tryon, V" uniqKey="Tryon V">V Tryon</name></author><author><name sortKey="Chandrasekar, V" uniqKey="Chandrasekar V">V Chandrasekar</name></author><author><name sortKey="Freeman, Gl" uniqKey="Freeman G">GL Freeman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Melby, Pc" uniqKey="Melby P">PC Melby</name></author><author><name sortKey="Chandrasekar, B" uniqKey="Chandrasekar B">B Chandrasekar</name></author><author><name sortKey="Zhao, W" uniqKey="Zhao W">W Zhao</name></author><author><name sortKey="Coe, Je" uniqKey="Coe J">JE Coe</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Menezes Sousa, D" uniqKey="Menezes Sousa D">D Menezes-Sousa</name></author><author><name sortKey="Correa Oliveira, R" uniqKey="Correa Oliveira R">R Corrêa-Oliveira</name></author><author><name sortKey="Guerra Sa, R" uniqKey="Guerra Sa R">R Guerra-Sá</name></author><author><name sortKey="Giunchetti, Rc" uniqKey="Giunchetti R">RC Giunchetti</name></author><author><name sortKey="Texeira Carvalho, A" uniqKey="Texeira Carvalho A">A Texeira-Carvalho</name></author><author><name sortKey="Martins Filho, Oa" uniqKey="Martins Filho O">OA Martins-Filho</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Menon, J" uniqKey="Menon J">J Menon</name></author><author><name sortKey="Bretscher, P" uniqKey="Bretscher P">P Bretscher</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Misra, A" uniqKey="Misra A">A Misra</name></author><author><name sortKey="Dube, A" uniqKey="Dube A">A Dube</name></author><author><name sortKey="Srivastava, B" uniqKey="Srivastava B">B Srivastava</name></author><author><name sortKey="Sharma, P" uniqKey="Sharma P">P Sharma</name></author><author><name sortKey="Srivastava, Jk" uniqKey="Srivastava J">JK Srivastava</name></author><author><name sortKey="Katiyar, Jc" uniqKey="Katiyar J">JC Katiyar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mookerjee, A" uniqKey="Mookerjee A">A Mookerjee</name></author><author><name sortKey="Sen, Pc" uniqKey="Sen P">PC Sen</name></author><author><name sortKey="Ghose, Ac" uniqKey="Ghose A">AC Ghose</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Moura, Tr" uniqKey="Moura T">TR Moura</name></author><author><name sortKey="Novais, Fo" uniqKey="Novais F">FO Novais</name></author><author><name sortKey="Oliveira, F" uniqKey="Oliveira F">F Oliveira</name></author><author><name sortKey="Clarencio, J" uniqKey="Clarencio J">J Clarêncio</name></author><author><name sortKey="Noronha, A" uniqKey="Noronha A">A Noronha</name></author><author><name sortKey="Barral, A" uniqKey="Barral A">A Barral</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mukbel, Rm" uniqKey="Mukbel R">RM Mukbel</name></author><author><name sortKey="Patten, C" uniqKey="Patten C">C Patten</name></author><author><name sortKey="Gibson, K" uniqKey="Gibson K">K Gibson</name></author><author><name sortKey="Ghosh, M" uniqKey="Ghosh M">M Ghosh</name></author><author><name sortKey="Petersen, C" uniqKey="Petersen C">C Petersen</name></author><author><name sortKey="Jones, De" uniqKey="Jones D">DE Jones</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Murray, Hw" uniqKey="Murray H">HW Murray</name></author><author><name sortKey="Masur, H" uniqKey="Masur H">H Masur</name></author><author><name sortKey="Keithly, Js" uniqKey="Keithly J">JS Keithly</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Murray, Hw" uniqKey="Murray H">HW Murray</name></author><author><name sortKey="Stem, Jj" uniqKey="Stem J">JJ Stem</name></author><author><name sortKey="Welte, K" uniqKey="Welte K">K Welte</name></author><author><name sortKey="Rubin, By" uniqKey="Rubin B">BY Rubin</name></author><author><name sortKey="Carreiro, Sm" uniqKey="Carreiro S">SM Carreiro</name></author><author><name sortKey="Nathan, Cf" uniqKey="Nathan C">CF Nathan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Murray, Hw" uniqKey="Murray H">HW Murray</name></author><author><name sortKey="Delph Etienne, S" uniqKey="Delph Etienne S">S Delph-Etienne</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Murray, Hw" uniqKey="Murray H">HW Murray</name></author><author><name sortKey="Berman, Jd" uniqKey="Berman J">JD Berman</name></author><author><name sortKey="Davies, Cr" uniqKey="Davies C">CR Davies</name></author><author><name sortKey="Saravia, Ng" uniqKey="Saravia N">NG Saravia</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nickol, Ad" uniqKey="Nickol A">AD Nickol</name></author><author><name sortKey="Bonventre, Pf" uniqKey="Bonventre P">PF Bonventre</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Niewiesk, S" uniqKey="Niewiesk S">S Niewiesk</name></author><author><name sortKey="Prince, G" uniqKey="Prince G">G Prince</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Norsworthy, Nb" uniqKey="Norsworthy N">NB Norsworthy</name></author><author><name sortKey="Sun, J" uniqKey="Sun J">J Sun</name></author><author><name sortKey="Elnaiem, D" uniqKey="Elnaiem D">D Elnaiem</name></author><author><name sortKey="Lanzaro, G" uniqKey="Lanzaro G">G Lanzaro</name></author><author><name sortKey="Soong, L" uniqKey="Soong L">L Soong</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Panaro, Ma" uniqKey="Panaro M">MA Panaro</name></author><author><name sortKey="Acquafredda, A" uniqKey="Acquafredda A">A Acquafredda</name></author><author><name sortKey="Lisi, S" uniqKey="Lisi S">S Lisi</name></author><author><name sortKey="Lofrumento, Dd" uniqKey="Lofrumento D">DD Lofrumento</name></author><author><name sortKey="Mitolo, V" uniqKey="Mitolo V">V Mitolo</name></author><author><name sortKey="Sisto, M" uniqKey="Sisto M">M Sisto</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Panaro, Ma" uniqKey="Panaro M">MA Panaro</name></author><author><name sortKey="Brandonisio, O" uniqKey="Brandonisio O">O Brandonisio</name></author><author><name sortKey="Caprerii, D" uniqKey="Caprerii D">D Caprerii</name></author><author><name sortKey="Cavallo, P" uniqKey="Cavallo P">P Cavallo</name></author><author><name sortKey="Cianciulli, A" uniqKey="Cianciulli A">A Cianciulli</name></author><author><name sortKey="Mitolo, V" uniqKey="Mitolo V">V Mitolo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Perez, Le" uniqKey="Perez L">LE Perez</name></author><author><name sortKey="Chandrasekar, B" uniqKey="Chandrasekar B">B Chandrasekar</name></author><author><name sortKey="Saldarriaga, Oa" uniqKey="Saldarriaga O">OA Saldarriaga</name></author><author><name sortKey="Zhao, W" uniqKey="Zhao W">W Zhao</name></author><author><name sortKey="Arteaga, Lt" uniqKey="Arteaga L">LT Arteaga</name></author><author><name sortKey="Travi, Bl" uniqKey="Travi B">BL Travi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pinelli, E" uniqKey="Pinelli E">E Pinelli</name></author><author><name sortKey="Killick Kendrick, R" uniqKey="Killick Kendrick R">R Killick-Kendrick</name></author><author><name sortKey="Wagenaar, J" uniqKey="Wagenaar J">J Wagenaar</name></author><author><name sortKey="Bernardina, W" uniqKey="Bernardina W">W Bernardina</name></author><author><name sortKey="Del Real, G" uniqKey="Del Real G">G Del Real</name></author><author><name sortKey="Ruitenberg, J" uniqKey="Ruitenberg J">J Ruitenberg</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pinelli, E" uniqKey="Pinelli E">E Pinelli</name></author><author><name sortKey="Gonzalo, Rm" uniqKey="Gonzalo R">RM Gonzalo</name></author><author><name sortKey="Boog, Cjp" uniqKey="Boog C">CJP Boog</name></author><author><name sortKey="Rutten, V" uniqKey="Rutten V">V Rutten</name></author><author><name sortKey="Gebhard, D" uniqKey="Gebhard D">D Gebhard</name></author><author><name sortKey="Del Real, G" uniqKey="Del Real G">G Del Real</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pinelli, E" uniqKey="Pinelli E">E Pinelli</name></author><author><name sortKey="Van Der Kaaij, Sy" uniqKey="Van Der Kaaij S">SY van der Kaaij</name></author><author><name sortKey="Slappendel, R" uniqKey="Slappendel R">R Slappendel</name></author><author><name sortKey="Fragio, C" uniqKey="Fragio C">C Fragio</name></author><author><name sortKey="Ruitenberg, Ej" uniqKey="Ruitenberg E">EJ Ruitenberg</name></author><author><name sortKey="Bernadina, W" uniqKey="Bernadina W">W Bernadina</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pinelli, E" uniqKey="Pinelli E">E Pinelli</name></author><author><name sortKey="Gebhard, D" uniqKey="Gebhard D">D Gebhard</name></author><author><name sortKey="Mommaas, Am" uniqKey="Mommaas A">AM Mommaas</name></author><author><name sortKey="Van Hoeij, M" uniqKey="Van Hoeij M">M van Hoeij</name></author><author><name sortKey="Langermans, J" uniqKey="Langermans J">J Langermans</name></author><author><name sortKey="Ruitenberg, Ej" uniqKey="Ruitenberg E">EJ Ruitenberg</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pinheiro, Phc" uniqKey="Pinheiro P">PHC Pinheiro</name></author><author><name sortKey="Dias, Ss" uniqKey="Dias S">SS Dias</name></author><author><name sortKey="Eulalio, Kd" uniqKey="Eulalio K">KD Eulálio</name></author><author><name sortKey="Mendonca, Il" uniqKey="Mendonca I">IL Mendonça</name></author><author><name sortKey="Katz, S" uniqKey="Katz S">S Katz</name></author><author><name sortKey="Barbieri, Cl" uniqKey="Barbieri C">CL Barbiéri</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Quinnell, Rj" uniqKey="Quinnell R">RJ Quinnell</name></author><author><name sortKey="Courtenay, O" uniqKey="Courtenay O">O Courtenay</name></author><author><name sortKey="Shaw, Ma" uniqKey="Shaw M">MA Shaw</name></author><author><name sortKey="Day, Mj" uniqKey="Day M">MJ Day</name></author><author><name sortKey="Garcez, Lm" uniqKey="Garcez L">LM Garcez</name></author><author><name sortKey="Dye, C" uniqKey="Dye C">C Dye</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Randolph, Se" uniqKey="Randolph S">SE Randolph</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Reithinger, R" uniqKey="Reithinger R">R Reithinger</name></author><author><name sortKey="Davies, Cr" uniqKey="Davies C">CR Davies</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Remme, Jhf" uniqKey="Remme J">JHF Remme</name></author><author><name sortKey="Blas, E" uniqKey="Blas E">E Blas</name></author><author><name sortKey="Chistulo, L" uniqKey="Chistulo L">L Chistulo</name></author><author><name sortKey="Desjeux, Pm" uniqKey="Desjeux P">PM Desjeux</name></author><author><name sortKey="Engers, Hd" uniqKey="Engers H">HD Engers</name></author><author><name sortKey="Kanyok, Tp" uniqKey="Kanyok T">TP Kanyok</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Roberts, M" uniqKey="Roberts M">M Roberts</name></author><author><name sortKey="Stober, C" uniqKey="Stober C">C Stober</name></author><author><name sortKey="Mckenzie, A" uniqKey="Mckenzie A">A Mckenzie</name></author><author><name sortKey="Blackwell, J" uniqKey="Blackwell J">J Blackwell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rodrigues Junior, V" uniqKey="Rodrigues Junior V">V Rodrigues Júnior</name></author><author><name sortKey="Silva, Js Da" uniqKey="Silva J">JS Da Silva</name></author><author><name sortKey="Campos Neto, A" uniqKey="Campos Neto A">A Campos-Neto</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rodriguez Roque, Al" uniqKey="Rodriguez Roque A">AL Rodríguez Roque</name></author><author><name sortKey="Cupolillo, E" uniqKey="Cupolillo E">E Cupolillo</name></author><author><name sortKey="Marchevssky, Rs" uniqKey="Marchevssky R">RS Marchevssky</name></author><author><name sortKey="Jasen, Am" uniqKey="Jasen A">AM Jasen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rogers, M" uniqKey="Rogers M">M Rogers</name></author><author><name sortKey="Kropf, P" uniqKey="Kropf P">P Kropf</name></author><author><name sortKey="Choi, B" uniqKey="Choi B">B Choi</name></author><author><name sortKey="Dillon, R" uniqKey="Dillon R">R Dillon</name></author><author><name sortKey="Podinovskaia, M" uniqKey="Podinovskaia M">M Podinovskaia</name></author><author><name sortKey="Bates, P" uniqKey="Bates P">P Bates</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sacks, D" uniqKey="Sacks D">D Sacks</name></author><author><name sortKey="Noben Trauth, N" uniqKey="Noben Trauth N">N Noben-Trauth</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Santaella, J" uniqKey="Santaella J">J Santaella</name></author><author><name sortKey="Ocampo, Cb" uniqKey="Ocampo C">CB Ocampo</name></author><author><name sortKey="Saravia, Ng" uniqKey="Saravia N">NG Saravia</name></author><author><name sortKey="Mendez, F" uniqKey="Mendez F">F Méndez</name></author><author><name sortKey="G Ngora, R" uniqKey="G Ngora R">R Góngora</name></author><author><name sortKey="Gomez, Ma" uniqKey="Gomez M">MA Gomez</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Satoskar, A" uniqKey="Satoskar A">A Satoskar</name></author><author><name sortKey="Bluethmann, H" uniqKey="Bluethmann H">H Bluethmann</name></author><author><name sortKey="Alexander, J" uniqKey="Alexander J">J Alexander</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Senior, K" uniqKey="Senior K">K Senior</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shweash, M" uniqKey="Shweash M">M Shweash</name></author><author><name sortKey="Mcgachy, Ha" uniqKey="Mcgachy H">HA McGachy</name></author><author><name sortKey="Schroeder, J" uniqKey="Schroeder J">J Schroeder</name></author><author><name sortKey="Neamatallah, T" uniqKey="Neamatallah T">T Neamatallah</name></author><author><name sortKey="Bryant, Ce" uniqKey="Bryant C">CE Bryant</name></author><author><name sortKey="Millington, O" uniqKey="Millington O">O Millington</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Soong, L" uniqKey="Soong L">L Soong</name></author><author><name sortKey="Chang, Ch" uniqKey="Chang C">CH Chang</name></author><author><name sortKey="Sun, J" uniqKey="Sun J">J Sun</name></author><author><name sortKey="Longley, Bj" uniqKey="Longley B">BJ Longley</name></author><author><name sortKey="Ruddle, Nh" uniqKey="Ruddle N">NH Ruddle</name></author><author><name sortKey="Flavell, Ra" uniqKey="Flavell R">RA Flavell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sosa Bibiano, Ei" uniqKey="Sosa Bibiano E">EI Sosa-Bibiano</name></author><author><name sortKey="Van Wynsberghe, Nr" uniqKey="Van Wynsberghe N">NR Van Wynsberghe</name></author><author><name sortKey="Canto Lara, Sb" uniqKey="Canto Lara S">SB Canto-Lara</name></author><author><name sortKey="Andrade Narvaez, Fj" uniqKey="Andrade Narvaez F">FJ Andrade-Narvaez</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Souza Lemos, C" uniqKey="Souza Lemos C">C Souza-Lemos</name></author><author><name sortKey="De Campos, Sn" uniqKey="De Campos S">SN De-Campos</name></author><author><name sortKey="Teva, A" uniqKey="Teva A">A Teva</name></author><author><name sortKey="Porrozzi, R" uniqKey="Porrozzi R">R Porrozzi</name></author><author><name sortKey="Grimaldi, G" uniqKey="Grimaldi G">G Grimaldi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Stamm, Lm" uniqKey="Stamm L">LM Stamm</name></author><author><name sortKey="R Is Nen Sokolowski, A" uniqKey="R Is Nen Sokolowski A">A Räisänen-Sokolowski</name></author><author><name sortKey="Okano, M" uniqKey="Okano M">M Okano</name></author><author><name sortKey="Russell, Me" uniqKey="Russell M">ME Russell</name></author><author><name sortKey="David, Jr" uniqKey="David J">JR David</name></author><author><name sortKey="Satoskar, Ar" uniqKey="Satoskar A">AR Satoskar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Szatkiewicz, Jp" uniqKey="Szatkiewicz J">JP Szatkiewicz</name></author><author><name sortKey="Beane, Gl" uniqKey="Beane G">GL Beane</name></author><author><name sortKey="Ding, Y" uniqKey="Ding Y">Y Ding</name></author><author><name sortKey="Hutchins, L" uniqKey="Hutchins L">L Hutchins</name></author><author><name sortKey="Pardo Manuel De Villena, F" uniqKey="Pardo Manuel De Villena F">F Pardo-Manuel de Villena</name></author><author><name sortKey="Churchill, Ga" uniqKey="Churchill G">GA Churchill</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nery Costa, Ch" uniqKey="Nery Costa C">CH Nery Costa</name></author><author><name sortKey="Peters, Nc" uniqKey="Peters N">NC Peters</name></author><author><name sortKey="Maruyama, Sr" uniqKey="Maruyama S">SR Maruyama</name></author><author><name sortKey="Brito, Ec De" uniqKey="Brito E">EC de Brito</name></author><author><name sortKey="Santos, Ik" uniqKey="Santos I">IK Santos</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Wynsberghe, Nr" uniqKey="Van Wynsberghe N">NR Van Wynsberghe</name></author><author><name sortKey="Canto Lara, Sb" uniqKey="Canto Lara S">SB Canto-Lara</name></author><author><name sortKey="Damian Centeno, Ag" uniqKey="Damian Centeno A">AG Damián-Centeno</name></author><author><name sortKey="Itza Ortiz, M" uniqKey="Itza Ortiz M">M Itzá-Ortiz</name></author><author><name sortKey="Andrade Narvaez, Fj" uniqKey="Andrade Narvaez F">FJ Andrade-Narváez</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Wynsberghe, Nr" uniqKey="Van Wynsberghe N">NR Van Wynsberghe</name></author><author><name sortKey="Canto Lara, Sb" uniqKey="Canto Lara S">SB Canto-Lara</name></author><author><name sortKey="Sosa Bibiano, Ei" uniqKey="Sosa Bibiano E">EI Sosa-Bibiano</name></author><author><name sortKey="Rivero Cardenas, Na" uniqKey="Rivero Cardenas N">NA Rivero-Cárdenas</name></author><author><name sortKey="Andrade Narvaez, Fj" uniqKey="Andrade Narvaez F">FJ Andrade-Narváez</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Villanueva Lizama, Le" uniqKey="Villanueva Lizama L">LE Villanueva Lizama</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vouldoukis, I" uniqKey="Vouldoukis I">I Vouldoukis</name></author><author><name sortKey="Drapier, Jc" uniqKey="Drapier J">JC Drapier</name></author><author><name sortKey="Nussler, Ak" uniqKey="Nussler A">AK Nüssler</name></author><author><name sortKey="Tselentis, Y" uniqKey="Tselentis Y">Y Tselentis</name></author><author><name sortKey="Silva, O Da" uniqKey="Silva O">O Da Silva</name></author><author><name sortKey="Gentilini, M" uniqKey="Gentilini M">M Gentilini</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wilson, Me" uniqKey="Wilson M">ME Wilson</name></author><author><name sortKey="Jeronimo, Smb" uniqKey="Jeronimo S">SMB Jeronimo</name></author><author><name sortKey="Pearson, Rd" uniqKey="Pearson R">RD Pearson</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="review-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Rev Inst Med Trop Sao Paulo</journal-id><journal-id journal-id-type="iso-abbrev">Rev. Inst. Med. Trop. Sao Paulo</journal-id><journal-title-group><journal-title>Revista do Instituto de Medicina Tropical de São Paulo</journal-title></journal-title-group><issn pub-type="ppub">0036-4665</issn><issn pub-type="epub">1678-9946</issn><publisher><publisher-name>Instituto de Medicina Tropical</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">24553602</article-id><article-id pub-id-type="pmc">4085833</article-id><article-id pub-id-type="publisher-id">S0036-46652014000100001</article-id><article-id pub-id-type="doi">10.1590/S0036-46652014000100001</article-id><article-categories><subj-group subj-group-type="heading"><subject>Review</subject></subj-group></article-categories><title-group><article-title>ANIMAL MODELS FOR THE STUDY OF LEISHMANIASIS
IMMUNOLOGY</article-title><trans-title-group xml:lang="es"><trans-title>Modelos animales para el estudio de la inmunología de la
leishmaniosis</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><name><surname>Loría-Cervera</surname><given-names>Elsy Nalleli</given-names></name><xref ref-type="aff" rid="aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Andrade-Narváez</surname><given-names>Fernando José</given-names></name><xref ref-type="aff" rid="aff1"></xref></contrib><aff id="aff1">Centro de Investigaciones Regionales “Dr. Hideyo Noguchi”, Mérida, Yucatán,<country>México</country></aff></contrib-group><author-notes><corresp>Elsy Nalleli Loría-Cervera, Universidad Autónoma de Yucatán, Centro de
Investigaciones Regionales “Dr. Hideyo Noguchi”, Laboratorio de Inmunología, Ave.
Itzáes No. 490 x 59-A, Mérida, Yucatán, México. Phone: 52-999 9246412 ext. 1155. Fax:
52-999 9236120. E-mail: <email>nalleli.cervera@uady.mx</email></corresp></author-notes><pub-date pub-type="epub-ppub"><season>Jan-Feb</season><year>2014</year></pub-date><pmc-comment>Fake ppub date generated by PMC from publisher
pub-date/@pub-type='epub-ppub' </pmc-comment>
<pub-date pub-type="ppub"><season>Jan-Feb</season><year>2014</year></pub-date><volume>56</volume><issue>1</issue><fpage>1</fpage><lpage>11</lpage><history><date date-type="received"><day>13</day><month>2</month><year>2013</year></date><date date-type="accepted"><day>28</day><month>5</month><year>2013</year></date></history><permissions><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc/3.0/"><license-p>This is an Open Access article distributed under the terms of the Creative
Commons Attribution Non-Commercial License, which permits unrestricted
non-commercial use, distribution, and reproduction in any medium, provided the
original work is properly cited.</license-p></license></permissions><abstract><p id="para1">Leishmaniasis remains a major public health problem worldwide and is
classified as Category I by the TDR/WHO, mainly due to the absence of control. Many
experimental models like rodents, dogs and monkeys have been developed, each with
specific features, in order to characterize the immune response to
<italic>Leishmania</italic> species, but none reproduces the pathology observed in
human disease. Conflicting data may arise in part because different parasite strains
or species are being examined, different tissue targets (mice footpad, ear, or base
of tail) are being infected, and different numbers (“low” 1×10<sup>2</sup> and “high”
1×10<sup>6</sup>) of metacyclic promastigotes have been inoculated. Recently, new
approaches have been proposed to provide more meaningful data regarding the host
response and pathogenesis that parallels human disease. The use of sand fly saliva
and low numbers of parasites in experimental infections has led to mimic natural
transmission and find new molecules and immune mechanisms which should be considered
when designing vaccines and control strategies. Moreover, the use of wild rodents as
experimental models has been proposed as a good alternative for studying the
host-pathogen relationships and for testing candidate vaccines. To date, using
natural reservoirs to study <italic>Leishmania</italic> infection has been
challenging because immunologic reagents for use in wild rodents are lacking. This
review discusses the principal immunological findings against
<italic>Leishmania</italic> infection in different animal models highlighting the
importance of using experimental conditions similar to natural transmission and
reservoir species as experimental models to study the immunopathology of the
disease.</p></abstract><trans-abstract xml:lang="es"><p id="para2">Las leishmaniosis siguen siendo un importante problema de salud pública a
nivel mundial y se clasifican como categoría I por el programa TDR/WHO, debido
principalmente a la ausencia de control. Muchos modelos experimentales tales como
roedores, perros y monos han sido desarrollados, cada uno con características
específicas, para caracterizar la respuesta inmune a las diferentes especies de
<italic>Leishmania</italic>, sin embargo ninguno reproduce la patología observada
en la enfermedad humana. La diversidad en los resultados obtenidos podría deberse en
parte a que diferentes cepas de parásitos o especies están siendo examinadas,
diferentes tejidos (cojinete plantar, oreja o base de la cola) han sido infectados y
diferente número (“bajo” 1×10<sup>2</sup> y “alto” 1×10<sup>6</sup>) de promastigotes
metacíclicos han sido inoculados. Recientemente, nuevos enfoques han sido propuestos
con el fin de obtener datos más significativos en cuanto a la respuesta inmune del
huésped y a la patogénesis, de tal forma que reproduzcan lo que ocurre en la
enfermedad humana. El uso de la saliva del insecto y de un número de parásitos menor
en las infecciones experimentales ha permitido reproducir la transmisión natural,
identificar nuevas moléculas, así como mecanismos inmunes que deberían ser
considerados en el diseño de vacunas y estrategias de control. Adicionalmente, se ha
propuesto como una buena alternativa el uso de roedores silvestres como modelos
experimentales tanto para el estudio de las relaciones huésped-patógeno como para
probar nuevas vacunas. A la fecha, el uso de reservorios naturales para estudiar la
infección por <italic>Leishmania</italic> ha sido un reto, debido a la carencia de
reactivos inmunológicos para uso en roedores silvestres. Esta revisión describe los
principales hallazgos inmunológicos ante la infección por
<italic>Leishmania</italic>, en los diferentes modelos animales, destacando la
importancia del uso de condiciones experimentales similares a la transmisión natural
y de reservorios como modelos experimentales para el estudio de la inmunopatología de
la enfermedad.</p></trans-abstract><kwd-group><kwd>Animal models</kwd><kwd><italic>Leishmania</italic></kwd><kwd>Immune response</kwd></kwd-group><counts><fig-count count="0"></fig-count><table-count count="0"></table-count><ref-count count="113"></ref-count><page-count count="11"></page-count></counts></article-meta></front><body><sec sec-type="intro"><title>INTRODUCTION</title><p id="para3">Leishmaniasis encompasses a group of diseases which are caused by infection
with protozoan parasites of the <italic>Leishmania</italic> (Kinetoplastida:
Trypanosomatidae) genus. They are still a major worldwide public health problem
considering they are endemic in 98 countries or territories, with more than 350 million
people at risk<sup>6</sup>. Moreover, it is estimated visceral leishmaniasis (VL) causes
over 50,000 deaths annually, a rate only surpassed, among parasitic diseases, by
malaria, and 2,357,000 disability-adjusted life years lost, placing leishmaniasis ninth
in a global analysis of infectious diseases<sup><xref rid="B06" ref-type="bibr">6</xref>,<xref rid="B28" ref-type="bibr">28</xref></sup>. Despite this very strong data, leishmaniasis is largely ignored in discussions
of tropical disease priorities and is one of the most neglected tropical diseases<sup><xref rid="B51" ref-type="bibr">51</xref>,<xref rid="B52" ref-type="bibr">52</xref></sup>. It has been pointed out that this consignment to critical oblivion possibly
“results from its complex epidemiology and ecology, the lack of simple, easily-applied
tools for case management and the paucity of current incidence data, and often results
in a failure on the part of policy-makers to recognize its importance<sup><xref rid="B05" ref-type="bibr">5</xref>,<xref rid="B14" ref-type="bibr">14</xref></sup>. Political and socioeconomic changes may have an even more important role than
global warming on the changing epidemiology of the leishmaniases, as has been argued for
tick-borne diseases in Europe<sup><xref rid="B91" ref-type="bibr">91</xref></sup>. The European Centre for Disease Prevention and Control lists the leishmaniases
among the ten vector-borne diseases that have the greatest potential to affect European inhabitants<sup><xref rid="B101" ref-type="bibr">101</xref></sup>.</p><p id="para4">The disease is transmitted to humans by sand flies and displays different
clinical manifestations, ranging from asymptomatic or subclinical infection to
disfiguring forms of cutaneous and mucosal leishmaniasis or potentially fatal visceral disease<sup><xref rid="B35" ref-type="bibr">35</xref>,<xref rid="B36" ref-type="bibr">36</xref>,<xref rid="B78" ref-type="bibr">78</xref>,<xref rid="B93" ref-type="bibr">93</xref></sup>. This polymorphic outcome has been considered to depend largely on the virulence
of the infecting parasite strain, immunoregulatory effects of sand fly saliva, as well
as the host's genetic background and immune response<sup><xref rid="B31" ref-type="bibr">31</xref>,<xref rid="B60" ref-type="bibr">60</xref>,<xref rid="B62" ref-type="bibr">62</xref></sup>. In summary, the leishmaniases remain as unpreventable and uncontrollable
diseases; moreover, their epidemiological profile is shifting towards an increased
prevalence, and therefore novel instruments and approaches to reach their control are
urgently necessary.</p><p id="para5">Leishmaniasis is most likely to be controlled by a successful vaccination
program. The relatively uncomplicated leishmanial life cycle and the fact that recovery
from a primary infection renders the host resistant to subsequent infections indicate
that a vaccine is feasible<sup><xref rid="B55" ref-type="bibr">55</xref></sup>. Many immunological aspects of the disease have been studied in experimental
animal models, such as mice, hamsters, domestic dogs and non-human primates. Although
most experimental models of leishmaniasis have the major advantage of allowing control
over the genetics of both the parasite and the host, none of them, in any way,
reproduces the outcome of human infection by <italic>Leishmania</italic> spp<sup><xref rid="B49" ref-type="bibr">49</xref></sup>.</p><p id="para6">Among the main factors contributing to differences between humans and animal
models are the size and nature of the inocula, the infection route and the strain of
host or parasite<sup><xref rid="B37" ref-type="bibr">37</xref>,<xref rid="B60" ref-type="bibr">60</xref>,<xref rid="B70" ref-type="bibr">70</xref></sup>. Currently, small numbers of <italic>in vitro</italic>-derived metacyclic
promastigotes together with strongly bioactive saliva, intradermal infection and host
reservoirs as experimental animal models are used to mimic the clinical and
immunological features found in human disease<sup><xref rid="B49" ref-type="bibr">49</xref></sup>. These approaches could contribute to developing improved experimental models for
studying leishmaniasis and identifying possible targets to evaluate vaccine
candidates.</p><p id="para7">The present review describes the most common animal experimental models which
have been employed to study the immune response to <italic>Leishmania</italic> spp. and
includes wild rodents. The main purpose is to discuss the concept of experimental animal
models to study leishmaniasis immunology.</p></sec><sec><title>MOUSE MODEL</title><p id="para8">The laboratory mouse owes much of its popularity as a model organism in
biomedical research to the existence of a large collection of inbred strains that
represent an immortal population of genetic clones derived by repeated brother sister
mating. Because mice from each strain are genetically identical it is possible to
collect and combine biological data over time and space leading to a depth of phenotype
characterization rarely achieved in other mammalian systems. Furthermore, the existence
of a definite set of genetic differences among inbred strains allows scientists to
explore the effect of genetic diversity on almost any phenotype of interest<sup><xref rid="B107" ref-type="bibr">107</xref></sup>. Another advantage of the murine model is the simplicity of keeping, breeding and
reproducing them<sup><xref rid="B47" ref-type="bibr">47</xref></sup>.</p><p id="para9">During the past 40 years, murine models of the human disease cutaneous
leishmaniasis have been extensively employed to elucidate the cell types, cytokines,
signal transduction cascades and antileishmanial effector mechanisms that are necessary
for the control of parasites, as well as for the clinical resolution of disease,
resistance to a secondary infection, and vaccine development<sup><xref rid="B18" ref-type="bibr">18</xref>,<xref rid="B73" ref-type="bibr">73</xref></sup>. Experimental infection of mice with <italic>L. major</italic> promastigotes has
allowed understanding of the immunologic mechanisms governing resistance (C57BL/6
strain) and susceptibility (BALB/c strain) to infection<sup><xref rid="B02" ref-type="bibr">2</xref></sup>.</p><p id="para10">Susceptibility has been correlated with the development of lesions
associated with a Th2 type of immune response, while the healing of lesions in resistant
mice has been correlated with the development of a Th1 type of immune response<sup><xref rid="B98" ref-type="bibr">98</xref></sup>. The resolution of lesions in C57BL/6 mice has been shown to involve several
factors contributing to the killing of <italic>L. major</italic> within macrophages. The
most efficient mechanism of parasite killing involves the production of gamma interferon
(IFN-γ) and tumor necrosis factor alpha (TNF-α) by CD4+ Th1 cells, which stimulate the
synthesis of inducible nitric oxide synthase (iNOS), generating the production of nitric
oxide (NO), a potent cytotoxin involved in the clearance or inhibition of
<italic>Leishmania</italic> parasites<sup><xref rid="B61" ref-type="bibr">61</xref>,<xref rid="B65" ref-type="bibr">65</xref>,<xref rid="B77" ref-type="bibr">77</xref></sup>.</p><p id="para11">In contrast, susceptible BALB/c mice develop severe and uncontrolled lesions
that lead to progressive disease and eventual death. This non-healer phenotype has been
shown to be associated with a parasite-specific Th2 response characterized by the
enhanced expression of deactivating macrophage cytokines such as interleukin 4 (IL-4),
interleukin 10 (IL-10) and transforming growth factor-β (TGF-β)<sup><xref rid="B11" ref-type="bibr">11</xref>,<xref rid="B94" ref-type="bibr">94</xref>,<xref rid="B98" ref-type="bibr">98</xref>,</sup>. Studies of mouse
models of leishmaniasis have provided important insights into the response of the host
to infection. However, the use of different parasite species, tissue targets (mice
footpad, ear, or base of tail) and doses (10<sup>5</sup> to 10<sup>7</sup>) of
metacyclic promastigotes has generated a wide variety of experiments that do not
reproduce the natural infection and cannot be extrapolated to human disease.’</p><p id="para12">In natural infections, the sand fly introduces into the skin a very small
number (possibly as few as 100 to 1,000) of metacyclic promastigotes together with
strongly bioactive saliva, whereas in laboratory infections thousands to millions of
culture-derived promastigotes or tissue-derived amastigotes are injected with a saline
solution or culture medium<sup><xref rid="B57" ref-type="bibr">57</xref></sup>.</p><p id="para13">In order to have a better understanding of natural
<italic>Leishmania</italic> infection in the laboratory, investigators are now using
small numbers of <italic>in vitro</italic>-derived metacyclic promastigotes and
intradermal rather than subcutaneous infection into the ears of mice<sup><xref rid="B49" ref-type="bibr">49</xref></sup>.</p><p id="para14">It was demonstrated, for example, that in mice inoculated with a mixture of
phlebotomine saliva and <italic>L. major</italic> promastigotes, the lesions grew faster
and were bigger than those of mice inoculated only with promastigotes<sup><xref rid="B13" ref-type="bibr">13</xref></sup>.</p><p id="para15">The ability of saliva to enhance <italic>Leishmania</italic> infection has
been attributed to modulation of the host immune system, potentially through
anti-inflammatory properties such as down regulation of antigen presentation,
co-stimulatory molecule expression, and nitric oxide production<sup><xref rid="B13" ref-type="bibr">13</xref>,<xref rid="B81" ref-type="bibr">81</xref></sup>. However, vaccination by pre-exposure to the bites of uninfected sand flies, with
whole saliva or with defined salivary proteins has shown to protect against cutaneous
<italic>L. major</italic> infection<sup><xref rid="B97" ref-type="bibr">97</xref></sup>. The frequent exposure to sand fly bites leads to the production of neutralizing
antibodies against salivary proteins and also to the activation of cellular mechanisms
that may have an adverse effect on <italic>Leishmania</italic> establishment. In this
perspective, characterization of immune responses against sand fly saliva can help
estimate both risk of infection and, to some degree, anti-parasite immunity. Although
this hypothesis has been proven in animal models, additional large-scale clinical
studies are necessary to validate it in humans<sup><xref rid="B15" ref-type="bibr">15</xref></sup>. Although the regulation of host immune response to <italic>Leishmania</italic>has been well defined in cutaneous <italic>L. major</italic> infection of inbred mice,
many studies have demonstrated that the host responses within the same mouse strain
could vary according to different <italic>Leishmania</italic> species. Different
virulence factors have been identified for distinct <italic>Leishmania</italic> species,
and there are profound differences in the immune mechanisms that mediate
susceptibility/resistance to infection and in the pathology associated with disease<sup><xref rid="B66" ref-type="bibr">66</xref></sup>. For example, C57BL/6 or C3H mice, which heal from <italic>L. major</italic>infection, develop chronic disease when infected with either <italic>L. (L.)
amazonensis</italic> or <italic>L. (L.) mexicana</italic>.</p><p id="para16">The characteristic chronic lesions of <italic>L. (L.) amazonensis</italic>infection in C57BL/6 and C57BL/10 mice are independent of IL-4 expression and
corresponding Th2 response<sup><xref rid="B01" ref-type="bibr">1</xref>,<xref rid="B54" ref-type="bibr">54</xref></sup>. In addition, <italic>L. (L.) amazonensis</italic> infection in C3H mice results
in low levels of production of IL-12 and IFN-γ by antigen-specific CD4+ T cells<sup><xref rid="B54" ref-type="bibr">54</xref></sup>. However, lesion development and parasite burden have been shown to be
exacerbated in the presence of CD4+ T cells, demonstrating that T cells are activated
during <italic>L. (L.) amazonensis</italic> infection and that they contribute
significantly to the immunopathology of chronic disease<sup><xref rid="B103" ref-type="bibr">103</xref></sup>.</p><p id="para17">Recently, it was demonstrated that susceptibility to <italic>L. (L.)
amazonensis</italic> in the mouse model of cutaneous leishmaniasis does not depend
only on the expression of IL-10. <italic>L. (L.) amazonensis</italic> parasites
persistent in IL-10-deficient mice; even in the presence of an enhanced Th1 response
during the early stages of infection and in the presence of antigen-specific cells
primed for Th1 effectors function during the chronic phase<sup><xref rid="B53" ref-type="bibr">53</xref></sup>.</p><p id="para18">Although the requirements for effective intracellular killing of <italic>L
(L.) amazonensis</italic> by activated macrophages are relatively unknown, it has
been demonstrated that the presence of both superoxide and nitric oxide is necessary for
efficient killing of amastigotes within LPS/IFN-γ–activated bone marrow-derived
macrophages generated from C3H mice<sup><xref rid="B74" ref-type="bibr">74</xref></sup>.</p><p id="para19">Control of the closely related <italic>L. (L.) mexicana</italic> in C57BL/6
mice has been shown to be IFN-γ and STAT4-dependent and surprisingly independent of
IL-12 production while the presence of IL-4, STAT6 and, perhaps as a consequence, the
ability to generate Th2 responses, are essential for the rapid lesion growth and
nonhealing responses<sup><xref rid="B21" ref-type="bibr">21</xref>,<xref rid="B100" ref-type="bibr">100</xref>,<xref rid="B106" ref-type="bibr">106</xref></sup>. Later on, it was demonstrated that endogenous IL-12 is only critical for
controlling the late but not the early stage of <italic>L. (L.) mexicana</italic>infection in C57BL/6 mice; however, they fail to resolve lesions, in contrast to
<italic>L. major</italic> infection<sup><xref rid="B03" ref-type="bibr">3</xref></sup>.</p><p id="para20">As an evasion mechanism, <italic>L. (L.) mexicana</italic> promastigotes
mediate the phosphorylation of specific transcription factors to enhance iNOS, COX-2 and
arginase-1 expression in LPS induced macrophages via TLR-4. The activities associated
with all three enzymes are the main factors leading to the downregulation of the IL-12
production in <italic>L. (L.) mexicana</italic> infected macrophages<sup><xref rid="B102" ref-type="bibr">102</xref></sup>.</p><p id="para21">The significant differences in the immune response between the Old World
(<italic>L. major</italic>) and New World (<italic>L. mexicana/L.
amazonensis</italic>) <italic>Leishmania</italic> species not only point to
interesting features of the host-pathogen interaction and immunobiology of this genus of
parasitic protozoa, but also have important implications for immunotherapy and vaccine
development. A view of leishmaniasis that only considers mouse model infection with
<italic>L. major</italic> misses a wealth of interesting immunobiology associated
with other species of <italic>Leishmania</italic><sup><xref rid="B66" ref-type="bibr">66</xref></sup>. Therefore, our understanding of the mechanisms involved in mucocutaneous and
cutaneous diseases caused by these organisms remains limited.</p><p id="para22">Mouse models have also been used to study visceral leishmaniasis caused by
both <italic>L. donovani</italic> and <italic>L. infantum</italic>. Although the outcome
of murine VL infection is genetically determined, most susceptible mouse strains
including BALB/c are able to control visceral disease<sup><xref rid="B75" ref-type="bibr">75</xref></sup>. Following <italic>Leishmania</italic> infection, BALB/c mice develop an
organ-specific immune response<sup><xref rid="B113" ref-type="bibr">113</xref></sup>. During the first weeks of infection, the parasites multiply rapidly in the
liver; however four weeks later, the mice develop an effective Th1 immune response,
clear the parasites and become resistant to reinfection<sup><xref rid="B76" ref-type="bibr">76</xref></sup>. The hepatic resistance to <italic>Leishmania</italic> infection in these mice is
associated with the development of a granulomatous reaction in the liver<sup><xref rid="B12" ref-type="bibr">12</xref></sup>. While pathology in the liver is limited, the parasites persist in the spleen and
the infection progresses for a longer period of time. Eventually, splenic replication is
controlled but parasites are usually maintained for life<sup><xref rid="B58" ref-type="bibr">58</xref></sup>. Parasite persistence in mice is accompanied by failure of granuloma formation
and splenomegaly<sup><xref rid="B39" ref-type="bibr">39</xref></sup>.</p><p id="para23">Due to the fact that visceral infection in BALB/c mice is chronic but not
fatal, it may be more appropriate to use it as a model for studying self-healing or
subclinical infection. Although experimental murine models of VL do not allow exact
extrapolations with subclinical infection in humans they have been useful to identify
genes and predict their functional roles in the protective immune response. Genetically
resistant mice have the functional <italic>NRAMP1</italic> gene which is involved in
macrophage activation<sup><xref rid="B16" ref-type="bibr">16</xref></sup>. The <italic>NRAMP1</italic> gene encodes a protein expressed on the membrane of
infected macrophages and exerts an enhanced effect on iNOS expression and generation of
NO, restricting intracellular <italic>Leishmania</italic> multiplication<sup><xref rid="B17" ref-type="bibr">17</xref></sup>. In this context, visceral infection in BALB/c mice provides a good model for the
evaluation of candidate vaccines.</p></sec><sec><title>HAMSTER MODEL</title><p id="para24">The Syrian golden hamster (<italic>Mesocricetus auratus</italic>) is highly
susceptible to infection with visceralizing <italic>Leishmania</italic> species
(<italic>L. donovani</italic>, <italic>L. infantum</italic>) and is considered the
best experimental model to study visceral leishmaniasis (VL) because it reproduces the
clinicopathological features of human disease. However, the wide use of hamsters is
still limited due to the scarcity of reagents (e.g., antibodies, cell markers and
cytokines) of defined specificity available to study the role of the immune response in
disease pathology<sup><xref rid="B48" ref-type="bibr">48</xref>,<xref rid="B68" ref-type="bibr">68</xref>,<xref rid="B113" ref-type="bibr">113</xref></sup>.</p><p id="para25">In 1978, CHANG & DWYER provided quantitative evidence indicating an avid
ingestion of <italic>L. donovani</italic> amastigotes by hamster macrophages and
supported the early findings that lysosome-phagosome fusion ocurrs<sup><xref rid="B26" ref-type="bibr">26</xref></sup>.</p><p id="para26">In order to understand the immune response to <italic>L. donovani</italic>infection the nucleotide sequences of several hamster cytokine genes (IL-2, IL-4, INF-γ,
TNF-α, IL-10, IL-12 and TGF-β) were cloned and used to analyze their expression in a
model of visceral infection. In this hamster model there was a pronounced expression of
the Th1 cytokine mRNAs (IL-2 and IFN-γ), with transcripts being detected as early as one
week post-infection. Surprisingly, although the basal expression of IL-4 was detected in
uninfected hamsters, their expression did not increase in response to infection with
<italic>L. donovani</italic>. IL-12 transcript expression was detected at low levels
starting seven days post-infection and its expression paralleled that of IFN-γ.
Additionally, the mRNA for TNF-α was increased within one week of infection but levels
did not increase further during the first month of infection. Expression of IL-10, a
potent macrophage deactivator, increased in splenic tissue over the first four weeks
after infection, suggesting that this cytokine could contribute to progressive disease
in hamsters. These studies provided the first description of the molecular
immunopathogenesis of disease in hamsters and indicated that progressive disease in this
model of VL is not associated with early polarization of the splenic cellular immune
response toward a Th2 phenotype and away from a Th1 phenotype, offering important
insights into human disease<sup><xref rid="B67" ref-type="bibr">67</xref></sup>.</p><p id="para27">During progressive disease in the hamster model of VL, uncontrolled parasite
replication in the liver, spleen, and bone marrow occurred despite the high activation
of the immune response and the strong Th1-like cytokine microenvironment. The failure in
the control of VL could be partially explained by the lymphoproliferative suppression
process which occurs during active disease<sup><xref rid="B45" ref-type="bibr">45</xref></sup>. Visceral infection caused by <italic>L. donovani</italic> led to a gradual
impairment of the proliferative response to parasite antigens in hamsters<sup><xref rid="B79" ref-type="bibr">79</xref></sup>. The latter dysfunction has been attributed to the inability of the infected
antigen-presenting cells (APCs) to stimulate specific T cells, the production of TGF-β
which triggers the apoptotic death of lymphocytes and the downregulation of protein
kinase C activity<sup><xref rid="B09" ref-type="bibr">9</xref>,<xref rid="B72" ref-type="bibr">72</xref>,<xref rid="B95" ref-type="bibr">95</xref></sup>. Interestingly, the antigen-dependent immunosuppression observed in <italic>L.
chagasi</italic>-infected hamsters with active visceral disease is not related to the
cytokine profile<sup><xref rid="B41" ref-type="bibr">41</xref></sup>.</p><p id="para28">Furthermore, the fatal outcome of the disease in the hamster model has been
related to the loss of macrophages effector functions. Indeed, throughout the course of
infection, inducible NO synthase (iNOS, NOS2) mRNA or enzyme activity in liver or spleen
tissue was not detected. Thus, although a Th1-like cytokine response was prominent, the
major antileishmanial effector mechanism that is responsible for control of infection in
mice was absent throughout the course of progressive VL in the hamster<sup><xref rid="B68" ref-type="bibr">68</xref></sup>.</p><p id="para29">Later on, it was shown that the lack of NO production was due to a defect in
the transcriptional activation of NOS2. Luciferase reporter assays demonstrated that the
hamster NOS2 promoter, like the human NOS2 promoter, has reduced basal and
IFN-γ/LPS-induced activity compared with the mouse promoter. The mechanism described
above is the most probable reason for the inability of hamsters to control
<italic>Leishmania</italic> infection<sup><xref rid="B84" ref-type="bibr">84</xref></sup>.</p><p id="para30">The role played by infected macrophages in the development of the cellular
unresponsiveness present in visceral leishmaniasis has been studied. Adherent spleen
cells from infected hamsters were unable to present <italic>L. donovani</italic>antigens to antigen specific T cells, however they were able to present KLH. Conversely,
T cells from infected animals did not respond to parasite antigens even when these
antigens were presented by normal syngeneic macrophages. Interestingly, lymphocytes from
inguinal lymph nodes of infected animals sensitized in their footpad with parasite
antigens proliferated well when stimulated <italic>in vitro</italic> with <italic>L.
donovani</italic> antigens. These results suggest that the defect in the cellular
immune response of the <italic>L. donovani</italic> infected hamsters is a consequence
of a selective inability of their antigen presenting cells to process and present
parasite antigens to T cells<sup><xref rid="B95" ref-type="bibr">95</xref></sup>.</p><p id="para31">To date, progressive disease in hamsters has been mostly achieved by the
injection of a large number of parasites via the i.v., intracardial, or i.p. routes.
However, these routes of infection do not mimic natural transmission by sand fly bite
where the parasites are delivered into the skin of a mammalian host in the presence of
saliva. Recently, it was demonstrated that a salivary protein of the sand fly vector
<italic>Lutzomia longipalpis</italic> protects against the fatal outcome of visceral
leishmaniasis caused by <italic>L. infantum</italic> in a hamster model. Immunization
with 16 DNA plasmids coding for salivary proteins of <italic>Lu. longipalpis</italic>resulted in the identification of LJM19, a novel 11-kDa protein, that protected hamsters
against the fatal outcome of VL. LJM19-immunized hamsters maintained a low parasite load
that correlated with an overall high IFN-γ/TGF-β ratio and iNOS expression in the spleen
and liver up to five months postinfection. Importantly, a delayed-type hypersensitivity
response with high expression of IFN-γ was also noted in the skin of LJM19-immunized
hamsters 48 hours after exposure to uninfected sand fly bites. Induction of IFN-γ at the
site of the bite could partly explain the protection observed in the viscera of
LJM19-immunized hamsters through direct parasite killing and/or priming of
anti-<italic>Leishmania</italic> immunity. These findings reinforce the concept of
using components of arthropod saliva in vaccine strategies against vector-borne diseases<sup><xref rid="B44" ref-type="bibr">44</xref></sup>.</p><p id="para32">To better understand the hamster immune response to important pathogens such
as <italic>Leishmania</italic>, a duplex real-time reverse transcriptase (RT) PCR assay
was developed for the relative quantification of the mRNAs of hamster cytokines,
chemokines, and related immune response molecules. The application of this assay to a
biological model was demonstrated in a cutaneous hamster model by comparing mRNA
expression in skin and lymph node tissues between uninfected and <italic>L.
panamensis</italic> infected hamsters. As a result, there was a relatively greater
basal expression in the LN compared to the skin for most transcripts (IL-4, CCR4, IL-21,
TNF-α, TGF-β, IFN-γ, IL-12p40, IL-10, and Foxp3). Conversely, the assay identified that
the basal expression of CCL22 and CCL17 mRNAs was significantly greater in the normal
skin compared to the LN. At an early stage of infection(one week p.i.) there was
concomitant upregulation of the type 1 (IFN-γ and IL-12p40) and type 2 (IL-4, IL-10,
IL-13, and IL-21) cytokines at the site of cutaneous infection, suggesting that a
balanced type 1 and type 2 cytokine response contributes to the chronicity of the
disease caused by <italic>L. panamensis</italic> in hamsters<sup><xref rid="B40" ref-type="bibr">40</xref></sup>.</p><p id="para33">Undoubtedly, the hamster model may be helpful for understanding the
immunological mechanisms involved in the pathogenesis of visceral leishmaniasis.
However, it is necessary to continue the efforts of producing specific reagents (i.e.
cytokine-specific and cell surface markers of monoclonal antibodies) and develop more
sensitive techniques that allow the study of the immunopathogenesis of the disease,
which has important implications for the generation of therapeutic and vaccine
targets.</p></sec><sec><title>DOG MODEL</title><p id="para34">Wild canines and domestic dogs are the main reservoirs of zoonotic visceral
leishmaniasis caused by <italic>L. infantum</italic> in the Mediterranean area,
Middle-East, Asian countries and Latin America. The role of dogs as the main reservoir
of visceral leishmaniasis has led to an increased interest in studying the immune
response and finding <italic>Leishmania</italic> antigens implicated in protective
cellular immunity in canine visceral leishmaniasis. Recent research has provided new
insights on the epidemiology, pathology and immunology of canine leishmaniasis and its
genetic basis. These new findings have led to better understanding of the disease, and
have also helped in the development of new diagnostic methods and control measures
against the infection, such as insecticide-impregnated collars for dogs, new drugs, and
second generation vaccines<sup><xref rid="B04" ref-type="bibr">4</xref>,<xref rid="B10" ref-type="bibr">10</xref></sup>.</p><p id="para35">Canine visceral leishmaniasis is a multisystemic disease with variable
clinical signs. Infected dogs may develop symptomatic infection resulting in death,
while others remain asymptomatic, or develop one or more mild symptoms and are
classified as oligosymptomatic<sup><xref rid="B27" ref-type="bibr">27</xref></sup>. The typical histopathological finding in the skin, liver and spleen, is a
granulomatous inflammatory reaction associated with the presence of
<italic>Leishmania</italic> amastigotes within macrophages<sup><xref rid="B10" ref-type="bibr">10</xref></sup>.</p><p id="para36">Studies on experimentally infected dogs have demonstrated that three years
after infection, asymptomatic or resistant dogs responded to <italic>L.
infantum</italic> antigen both in lymphocyte proliferation assays <italic>in
vitro</italic> and in delayed-type hypersensitivity reaction, whereas no serum
antibodies to parasite antigen were shown. In contrast, symptomatic or susceptible
animals failed to respond to the parasite antigen in cell-mediated assays both
<italic>in vitro</italic> and <italic>in vivo</italic> and showed considerably higher
serum antibodies to leishmanial antigens, which are not immunoprotective. In addition,
peripheral mononuclear cells from asymptomatic dogs produced significantly higher levels
of IL-2 and TNF-α than symptomatic and control uninfected dogs. Similar results were
observed with a group of mixed-breed dogs with natural <italic>Leishmania</italic>infections, also grouped as asymptomatic or symptomatic on the basis of clinical signs
of canine visceral leishmaniasis<sup><xref rid="B85" ref-type="bibr">85</xref></sup>.</p><p id="para37">The main effector mechanism involved in the protective immune response of
dogs infected with <italic>L. infantum</italic> is the activation of macrophages by
IFN-γ and TNF-α to kill intracellular amastigotes via the L-arginine nitric oxide
pathway, as has been observed following successful chemotherapy of <italic>L.
infantum</italic>-infected dogs<sup><xref rid="B112" ref-type="bibr">112</xref></sup>. NO production and anti-leishmanial activity has also been detected in a canine
macrophage cell line infected with <italic>L. infantum</italic> after incubation with
IFN-γ, TNF-α and IL-2<sup>88</sup>, as well as in macrophages from dogs immunized with
killed <italic>L.infantum</italic> promastigotes<sup><xref rid="B82" ref-type="bibr">82</xref></sup>. Later on, it was demonstrated that NO production may be involved in the
long-term protection of dogs against natural <italic>Leishmania</italic> infection and
in the clinical presentation of canine leishmaniasis<sup><xref rid="B83" ref-type="bibr">83</xref></sup>.</p><p id="para38">The local tissue cytokine response of dogs naturally infected with
<italic>L. infantum</italic> has been evaluated. The analysis revealed an enhanced
INF-γ mRNA accumulation in infected dogs which was positively correlated with humoral,
(IgG1) but not with lymphoproliferative, responses to the <italic>Leishmania</italic>antigen. However, infected dogs with detectable IL-4 mRNA had significantly more severe symptoms<sup><xref rid="B90" ref-type="bibr">90</xref></sup>. A balanced production of Th1 and Th2 cytokines was detected in the spleen of
<italic>L. infantum</italic> infected dogs, with a predominant accumulation of mRNA
for IL-10 and IFN-γ that was related to the parasitic load and to clinical progression<sup><xref rid="B59" ref-type="bibr">59</xref></sup>. Additionally, a mixed cytokine profile with high levels of expression of IFN-γ,
TNF-α and IL-13 was determined in the skin of asymptomatic dogs naturally infected with
<italic>L. infantum</italic>. Moreover, the levels of transcription factors GATA-3
and FOXP3 were correlated with the asymptomatic disease. These results indicate that in
addition to the mixed cytokine profile, the enhanced expression of their associated
transcription factors plays an important role in the clinical status of
<italic>Leishmania</italic> infected dogs<sup><xref rid="B69" ref-type="bibr">69</xref></sup>. The role of Th2 type cytokines in canine VL has not yet been defined. Evidence
for Th1 and Th2 mixed responses has been reported in antigen-stimulated PBMC from
asymptomatic dogs experimentally infected with <italic>L. infantum</italic>, which
displayed IL-2, IFN-γ and IL-10 mRNA transcripts. However, IL-2 and IFN-γ predominated
in asymptomatic dogs and the development of symptomatic infections could not be related
to IL-10 expression<sup><xref rid="B25" ref-type="bibr">25</xref></sup>. IL-10 mRNA transcripts were detected in Con A-stimulated PBMC derived from dogs
with clinical signs of VL<sup><xref rid="B87" ref-type="bibr">87</xref></sup>. All of these results are in agreement with experiments in which PBMC obtained
from symptomatic VL dogs were stimulated by a recombinant <italic>L. infantum</italic>cysteine proteinase and high levels of IL-10 were detected by an ELISA assay. In
contrast, low or undetectable concentrations of this cytokine were found in PBMC
supernatants from oligosymptomatic and asymptomatic animals, respectively<sup><xref rid="B89" ref-type="bibr">89</xref></sup>.</p><p id="para39">Although IL-10 secreted by CD25+ CD4+-regulatory T cells has been implicated
in murine and human leishmaniasis, the involvement of these cells in canine visceral
leishmaniasis has not been explored.</p><p id="para40">Few studies have demonstrated the involvement of CD8+ lymphocytes in
resistance to canine VL. These lymphocytes were detected in asymptomatic dogs
experimentally infected with <italic>L. infantum</italic> but not in symptomatic
animals, suggesting that direct lysis of <italic>L. infantum</italic>-infected
macrophages by cytotoxic T lymphocytes represents an additional effector mechanism in
resistance to VL<sup><xref rid="B86" ref-type="bibr">86</xref></sup>. In dogs naturally infected with <italic>L. infantum</italic>, a reduction in
both CD4+ and CD8+ populations was observed, while restoration of these cells occurred
after drug treatment<sup><xref rid="B19" ref-type="bibr">19</xref></sup>.</p><p id="para41">The use of dogs as experimental models to study visceral leishmaniasis has
led to elucidate the role of immune cells and their principal products to better
understand the possible mechanisms mediating immune response during
<italic>Leishmania</italic> infection, which may contribute to the development of
vaccines or immunotherapy.</p><p id="para42">Natural infection of domestic dogs with <italic>L. (V.)
braziliensis</italic>, <italic>L. (V.) peruviana</italic>, <italic>L. (V.)
panamensis</italic>, <italic>L. (V.) colombiensis</italic> and <italic>L. (L.)
mexicana</italic> has been reported in Latin America<sup><xref rid="B30" ref-type="bibr">30</xref></sup>. To date, there is no solid evidence that dogs act as reservoir hosts for the
domestic transmission of CL<sup><xref rid="B92" ref-type="bibr">92</xref>,<xref rid="B99" ref-type="bibr">99</xref></sup>. Most studies are designed to determine the prevalence of CL in dogs, however,
little is known about the parasitologic and immunologic course of infection.</p></sec><sec><title>NON-HUMAN PRIMATE MODEL</title><p id="para43">Non-human primates are valuable models for biomedical research because of
their similarities to humans in anatomy, immunology and physiology. However, they are
expensive laboratory animals that are difficult to obtain and to handle. Availability of
a non-human primate model of leishmaniasis would facilitate the study of different
aspects of this disease and would accelerate the development of vaccines and testing of
new drug candidates.</p><p id="para44">The Asian rhesus macaques (<italic>Macaca mulatta</italic>) are quite
susceptible to <italic>Leishmania</italic> infection: they develop a human-like disease,
exhibit antibodies to <italic>Leishmania</italic> and parasite-specific T-cell mediated
immune responses both <italic>in vivo</italic> and <italic>in vitro</italic>, and can be
protected effectively by vaccination<sup><xref rid="B46" ref-type="bibr">46</xref></sup>. Distinct histopathological patterns were observed in <italic>Macaca
mulatta</italic> lesions at biopsy, but healing lesions contained more organized
epithelioid granulomas and activated macrophages, followed by fibrotic substitution in
response to <italic>L. (L.) amazonensis</italic> infection<sup><xref rid="B07" ref-type="bibr">7</xref></sup>. Interestingly in <italic>L. (V.) braziliensis</italic> infection, the presence
of antigen-specific IFN-γ or TNF-α-producing CD4+ and CD8+ cells are likely important
for the immunological effectiveness of granulomas. However, their resolution can be
attributed to the concomitant recruitment of IL-10-producing CD4+CD25+ regulatory T
cells that suppress the effector T-cell mediated inflammatory response<sup><xref rid="B32" ref-type="bibr">32</xref>,<xref rid="B105" ref-type="bibr">105</xref></sup>. The progression and resolution of skin lesions caused by both
<italic>Leishmania</italic> species appears to be very similar to that observed in
humans, confirming the potential for this monkey as a viable surrogate to study the
immune response in human cutaneous leishmaniasis<sup><xref rid="B07" ref-type="bibr">7</xref></sup>.</p><p id="para45">Macaques have also been used to explore immune response against <italic>L.
major</italic> infection. Infected animals develop a simple cutaneous lesion which
progresses spontaneously to ulceration and complete resolution within about three months
which is associated with a non-specific chronic inflammation and/or tuberculoid-type
granulomatous reaction. Additionally, macaques develop varying levels of resistance
against homologous re-infection as it happens in humans. Thus, the importance of this
model in experimental CL lies in the reproduction of clinical and histopathological
features that are common in <italic>L. major</italic>-infected humans and in the
resistance to secondary infection, indicating the development of an acquired immunity<sup><xref rid="B08" ref-type="bibr">8</xref></sup>.</p><p id="para46">New World primates, such as owl monkeys <italic>(Aotus
trivirgatus),</italic> squirrel monkeys <italic>(Saimiri sciureus),</italic> and
marmosets <italic>(Callithrix jaccus jaccus)</italic> have been considered potential
hosts for studying visceral leishmaniasis. Owl monkeys develop a visceral disease
characterized by weight loss, anemia and hepatosplenomegaly. Its high susceptibility to
<italic>L. donovani</italic> infection suggest it may be useful for the study of VL<sup><xref rid="B20" ref-type="bibr">20</xref></sup>. In contrast, squirrel monkeys develop a visceral disease when infected with
<italic>L. donovani</italic> but are able to recover from disease and became
resistant to reinfection<sup><xref rid="B34" ref-type="bibr">34</xref></sup>.</p><p id="para47">Although little is known about immune response to
<italic>Leishmania</italic> infection in monkeys, they are frequently used as models
for preclinical testing of <italic>Leishmania</italic> candidate vaccines. The safety,
immunogenicity, and efficacy of a vaccine combining heat-killed <italic>L. (L.)
amazonensis</italic> with human rIL-12 (rhIL-12) and alum (aluminium hydroxide gel)
as adjuvants was evaluated in rhesus macaques. The single s.c. vaccination was found to
be safe and immunogenic, although a small transient s.c. nodule developed at the
vaccination site. Groups receiving rhIL-12 had an augmented <italic>in vitro</italic>Ag-specific IFN-γ response after vaccination, as well as increased production of IgG.
Furthermore, intradermal forehead challenge infection with 10<sup>7</sup> metacyclic
<italic>L. (L.) amazonensis</italic> promastigotes at four weeks demonstrated
protective immunity in all monkeys receiving rhIL-12 with alum and Ag. Thus, a single
dose vaccine with heat-killed <italic>Leishmania</italic> using rhIL-12 and alum as
adjuvants was safe and fully protective in a primate model of cutaneous leishmaniasis<sup><xref rid="B56" ref-type="bibr">56</xref></sup>.</p><p id="para48">Successful vaccination has been achieved against visceral leishmaniasis by
intradermal inoculation of alum-precipitated autoclaved <italic>L. major</italic> with
BCG (bacile Calmette-Guérrin) and autoclaved <italic>L. donovani</italic> with BCG in
Indian langurs. Vaccinated animals show a delayed protection and significant
lymphoproliferative response with high levels of IFN-γ and IL-2<sup><xref rid="B38" ref-type="bibr">38</xref>,<xref rid="B71" ref-type="bibr">71</xref></sup>.</p><p id="para49">Attempts were made to reproduce the spectrum of human visceral leishmaniasis
due to <italic>L. donovani</italic> in Vervet monkeys (<italic>Chlorocebus
pygerythrus</italic>). Both symptomatic and asymptomatic/cryptic infections were
observed. However asymptomatic infected animals had competent humoral and cellular
responses to homologous parasites<sup><xref rid="B43" ref-type="bibr">43</xref></sup>.</p><p id="para50">The development of a non-human primate model of leishmaniasis, which largely
mimics the human situation, is described for studies of different aspects of the disease
that would not be possible in humans for ethical reasons. However, for financial and
ethical reasons, the use of primates in biomedical research is limited. Studies
involving these animals have, therefore, been tailored to solve questions that cannot be
answered in other animals. Monkeys are normally the final experimental animals to be
used in studies of the safety and efficacy of vaccines and drugs developed in other
laboratory animals<sup><xref rid="B48" ref-type="bibr">48</xref></sup>.</p></sec><sec><title>WILD RODENTS</title><p id="para51">Classical laboratory inbred strains of mice have been extremely helpful for
research in immunology and oncology. Unfortunately, because they all derive from a
relatively small pool of ancestors, their genetic polymorphism is rather limited<sup><xref rid="B47" ref-type="bibr">47</xref></sup>.</p><p id="para52">A new approach to study host-parasite relationships has been the use of wild
rodents, particularly primary reservoirs, as experimental animal models. They are, as
the human being, genetically polymorphic and represent an emerging system for the
genetic analyses of the physiological and behavioral bases of habitat adaptation<sup><xref rid="B47" ref-type="bibr">47</xref></sup>. Laboratory studies using natural hosts as experimental models provide a suitable
indication of the importance of these hosts as reservoirs, since it allows a better
understanding of the dynamics of infection, especially concerning the ability to retain
the infection and amplify parasite populations in a given environment, due to features
that favor parasite transmission (e.g., presence of parasites in the skin). Moreover,
the study of these rodents could allow the understanding of the mechanisms involved in
immune activation during nonpathogenic and pathogenic infections, to clarify how the
reservoir immune response regulates <italic>Leishmania</italic> infection and how the
parasites evade a sterilizing immune response.</p><p id="para53">The role of several species of rodents as wild reservoirs of
<italic>Leishmania</italic> species is well known<sup><xref rid="B24" ref-type="bibr">24</xref>,<xref rid="B33" ref-type="bibr">33</xref>,<xref rid="B96" ref-type="bibr">96</xref>,<xref rid="B110" ref-type="bibr">110</xref></sup>. However, there are only a few studies that followed up experimentally infected
wild hosts by <italic>Leishmania</italic> species, mostly due to the difficulties of
managing wild mammals in captivity. To date the host-parasite interactions involved in
persistent infections in different <italic>Leishmania</italic> reservoirs are
unknown.</p><p id="para54"><italic>Sigmodon hispidus</italic> has been identified as <italic>Leishmania</italic>reservoir, however no studies of experimental infection have been carried out with this pathogen<sup><xref rid="B33" ref-type="bibr">33</xref></sup>. Currently <italic>Sigmodon hispidus</italic> is used as a model for the study of
various infectious diseases, mainly caused by viruses and bacteria, due to its high
susceptibility to a wide variety of pathogens<sup><xref rid="B80" ref-type="bibr">80</xref></sup>. A large number of cytokine and chemokine genes have been cloned and sequenced
and monoclonal antibodies have been generated in order to facilitate its use as an
experimental animal model. Recently, low levels of NO production and iNOS expression
similar to human macrophages were found in <italic>Sigmodon hispidus</italic> infected
with bacteria<sup><xref rid="B23" ref-type="bibr">23</xref></sup>. These similarities could explain the high susceptibility of this rodent to human
pathogens.</p><p id="para55"><italic>Thrichomys laurentius</italic> is a South American caviomorph rodent formerly
included in a monospecific genus, in which the importance of the retention of infection
and transmission of <italic>Leishmania</italic> species has been established. These
rodents were found infected with <italic>Leishmania</italic> species of different
complexes – <italic>L. (L.) mexicana</italic> and <italic>L. donovani</italic> – in an
endemic area of both visceral and tegumentary leishmaniasis in Brazil.
<italic>Thrichomys laurentius</italic> was adapted to captivity and experimental
patterns of <italic>L. infantum</italic> and <italic>L. braziliensis</italic> infections
were identified in this rodent. Both <italic>Leishmania</italic> species demonstrated
the ability to invade and persist in the viscera and skin of <italic>T.
laurentius</italic>, yet no rodent displayed skin lesions, histological changes in
skin, spleen or liver, nor clinical evidence of infection<sup><xref rid="B96" ref-type="bibr">96</xref></sup>.</p><p id="para56">In the Yucatan peninsula of Mexico, <italic>Peromyscus yucatanicus</italic>has been identified as primary reservoir of <italic>L. (L.) mexicana</italic><sup><xref rid="B22" ref-type="bibr">22</xref>,<xref rid="B109" ref-type="bibr">109</xref></sup>. It has been adapted to the laboratory and a colony was established for
experimental studies. <italic>P. yucatanicus</italic> inoculated with 10<sup>6</sup>promastigotes of <italic>L. (L.) mexicana</italic> on the base of the tail reproduced
both the clinical and histopathological picture of CL in humans, supporting its utility
as a novel experimental model to study CL caused by <italic>L. (L.) mexicana</italic><sup><xref rid="B104" ref-type="bibr">104</xref></sup>. Moreover 100% of <italic>P. yucatanicus</italic> inoculated with 10<sup>2</sup>(“low inoculum”) developed subclinical infection (absence of clinical signs and evidence
of parasite's DNA at the site of inocula) and when immunosupressed with cyclophosphamide
a reactivation with the appearance of lesions was observed<sup><xref rid="B29" ref-type="bibr">29</xref></sup>. Nitric oxide production was documented in co-cultured macrophages and
lymphocytes from <italic>P. yucatanicus</italic> with clinical and subclinical infection
caused by <italic>L. (L.) mexicana</italic><sup><xref rid="B64" ref-type="bibr">64</xref></sup>. Although NO production was observed in these wild rodents, they were unable to
clear the infection, which differs with the response observed in murine models where the
generation of NO is the main effector mechanism involved in the control of <italic>L.
major</italic> infection. Similarly, the role of this cytotoxic molecule in the
antileishmanial activity of human macrophages remains controversial<sup><xref rid="B42" ref-type="bibr">42</xref></sup>.</p><p id="para57">Recently cDNAs of Th1, Th2 and Th17 cytokines have been amplified from
<italic>P. yucatanicus</italic> spleen cells by PCR using <italic>P.
maniculatus</italic> primers cloned into TOPO TA cloning vector and sequenced<sup><xref rid="B63" ref-type="bibr">63</xref>,<xref rid="B111" ref-type="bibr">111</xref></sup>. These results strongly support employing <italic>P. maniculatus</italic>specific primers to study the kinetics of cytokines involved in the immune response
against clinical and subclinical <italic>L. (L.) mexicana</italic> infection in
<italic>P. yucatanicus</italic>. This approach will allow the quantifying and
analyzing of the expression of important cytokines, transcription factors and cellular
markers involved in the immune response to <italic>L. (L.) mexicana</italic> infection
in a specific manner. It will also permit to determine the immune response leading to
the clinical and subclinical infection in Yucatan deer mice and compare with the immune
response observed in humans, in order to confirm its importance as an experimental model
to study LCL caused by <italic>L. (L.) mexicana</italic>.</p></sec><sec sec-type="conclusions"><title>CONCLUSIONS</title><p id="para58">First of all, there is a worldwide agreement regarding the concept that
experimental animal models are expected to mimic the pathological features and
immunological responses observed in humans when exposed to a variety of
<italic>Leishmania</italic> spp. with different pathogenic characteristics<sup><xref rid="B50" ref-type="bibr">50</xref></sup>. This approach deserves to be re-analyzed based on updated studies.</p><p id="para59">What does it mean to “mimic the patholgical features”? It is clear to date
that the outcomes of the infection depend on a variety of factors in each particular
laboratory animal including: a) the <italic>Leishmania</italic> spp. inoculated; b) the
virulence of the parasite isolate used; c) the parasite stage, via, size, and route of
the inoculum. In addition, the nature of each laboratory animal, i.e. the genetic makeup
that relates to the immunological background, which plays an important role in
host-parasite realtionships. Moreover, when we say “leishmaniasis” as so “the
leishmaniases”, we are referring to a group of diseases that are caused by different
species of protozoan parasites of the genus <italic>Lesihmania</italic>. We have been
trying (as it has been done in other pathologies such as “cancer”) to include different
diseases as a single pathological entity. Therefore, shouldn't we develop a different
experimental animal model for each leishmaniasis?</p><p id="para60">It is well known that infection begins when an infected female sand fly
takes a blood meal from a human host in a leishmaniasis endemic area. Following
inoculation into the skin by the sand fly bite, the flagellated promastigotes penetrate
into the macrophage, transform into amastigotes and multiply. The infected macrophage
eventually bursts and the released parasites are able to infect new phagocytic cells.
When the infected host is bitten by another female sand fly, parasites are ingested and
the life cycle continues. The course of the disease is variable ranging from spontaneous
healing to chronicity, but most infected individuals remain asymptomatic or subclinical.
Therefore, there is a wide infection spectrum as a result of the parasite inoculation.
As a consequence it is necessary to study the significance of subclinical infection in
humans and other hosts. Therefore, when building a “good” animal model to study
leishmaniasis immunology, should we consider all the possible outcomes of the
<italic>Leishmania</italic> spp. infection, particularly subclinical infection?</p><p id="para61">With reference to the suggested requirement to “mimic immunological
responses observed in humans” when exposed to a particular <italic>Leishmania</italic>spp., the problem becomes more complex if we consider that it varies depending on
multiple factors according to present knowledge of the host-parasite interaction. In a
recent work of the Working Group on research Priorities for Development of Leishmania
Vaccines, a good review was made on vaccine trials in the last three decades, the
profile of strategies, and animal models used in leishmaniasis trials<sup><xref rid="B108" ref-type="bibr">108</xref></sup>. The main questions raised encompassed issues concerning all of the
leishmaniases. They have addressed the employment of live attenuated or genetically
modified parasites, the role of vectors, and elucidation of protective immunity.
Regarding the last issue, they considered it crucial to test vaccine candidates in
different models using different species, and to test the effects of including salivary
proteins of vectors. The major challenge is the absence of an experimental animal model
that mimics the whole picture of human leishmaniasis, i.e. different subclinical and
clinical outcomes and protective immune response. This situation leads to the necessary
development of research studies focused mainly on building new animal models capable of
evaluating the same criteria in both models and humans.</p><p id="para62">The use of wild rodents, primary reservoirs, as experimental models for
studying <italic>Leishmania</italic> infection could be very useful to elucidate their
role as reservoirs so as to improve our knowledge about the parasite-vector and
parasite-host relationship, in order to understand what happens in human
<italic>Leishmania</italic> infections.</p></sec><sec><title>FINAL CONSIDERATIONS AND PERSPECTIVES</title><p id="para63">The use of experimental animal models remains a good alternative for
designing immunological studies that, for ethical reasons, cannot be performed in
humans. Certainly, the increased interest in studying the immune response against
<italic>Leishmania</italic> infection in different animal models has contributed to
our understanding of parasite-host relationship. However no model can develop all the
possible outcomes of the <italic>Leishmania</italic> infection or entirely reproduce the
disease in humans. Thus, there are still so many questions to answer in order to find
control strategies or a successful vaccination program.</p><p id="para64">Although mouse model has widely contributed to the understanding of immune
response against <italic>L. major</italic> infection many studies have demonstrated
profound differences in the immune mechanisms related to infections with New World
<italic>Leishmania</italic> species. Furthermore, visceral infection in mice does not
mimic the pathological features and immunological responses observed in human cases. The
hamster result is a better model to study the progressive disease of visceralizing
<italic>Leishmania</italic> spp. The lack of reagents for immunological analysis and
the strong immunosuppression of the lymphoproliferative response in hamsters make
difficult its use for the evaluation of vaccine candidates. The increased interest of
researchers to use dogs as experimental models lies in the possibility of studying the
immune response in natural infection. Since dogs are important reservoirs of
visceralizing <italic>Leishmania</italic>, vaccination of these animals would constitute
a major step towards the control of human infections. Finally, the use of monkeys has
been explored for testing vaccine candidates, however little is known as to whether the
immune response to <italic>Leishmania</italic> infection is similar to that observed in
humans.</p><p id="para65">In order to obtain more meaningful data regarding immune response that
parallels human disease it is very important to continue with the efforts in developing
strategies to mimic natural transmission such as the use of low infectious doses,
bioactive saliva and natural reservoir hosts to have a better approximation of the
dynamics of natural infection. These approaches could contribute to developing improved
experimental models for studying leishmaniasis and identifying possible targets to
evaluate vaccine candidates.</p></sec></body><back><ack><p id="para66">To Dr. Bruno Travi for editing the manuscript.</p></ack><ref-list><title>REFERENCES</title><ref id="B01"><label>1</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Afonso</surname><given-names>LC</given-names></name><name><surname>Scott</surname><given-names>P</given-names></name></person-group><article-title>Immune responses associated with susceptibility of
C57BL/10 mice to <italic>Leishmania amazonensis</italic></article-title><source>Infect Immun</source><year>1993</year><volume>61</volume><fpage>2952</fpage><lpage>2959</lpage><pub-id pub-id-type="pmid">8514400</pub-id></element-citation></ref><ref id="B02"><label>2</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Aguilar-Torrentera</surname><given-names>F</given-names></name><name><surname>Carlier</surname><given-names>Y</given-names></name></person-group><article-title>Immunological factors governing resistance and
susceptibility of mice to <italic>Leishmania major</italic>infection</article-title><source>Rev Latinoam Microbiol</source><year>2001</year><volume>43</volume><fpage>135</fpage><lpage>142</lpage><pub-id pub-id-type="pmid">17061500</pub-id></element-citation></ref><ref id="B03"><label>3</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Aguilar-Torrentera</surname><given-names>F</given-names></name><name><surname>Laman</surname><given-names>JD</given-names></name><name><surname>Van Meurs</surname><given-names>M</given-names></name><name><surname>Adorini</surname><given-names>L</given-names></name><name><surname>Muraille</surname><given-names>E</given-names></name><name><surname>Carlieri</surname><given-names>Y</given-names></name></person-group><article-title>Endogenous interleukin-12 is critical for controlling
the late but not the early stage of <italic>Leishmania mexicana</italic> infection
in C57BL/6 mice</article-title><source>Infect Immun</source><year>2002</year><volume>70</volume><fpage>5075</fpage><lpage>80</lpage><pub-id pub-id-type="pmid">12183555</pub-id></element-citation></ref><ref id="B04"><label>4</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Alvar</surname><given-names>J</given-names></name><name><surname>Cañavate</surname><given-names>C</given-names></name><name><surname>Molina</surname><given-names>R</given-names></name><name><surname>Moreno</surname><given-names>J</given-names></name><name><surname>Nieto</surname><given-names>J</given-names></name></person-group><article-title>Canine leishmaniasis</article-title><source>Adv Parasitol</source><year>2004</year><volume>57</volume><fpage>1</fpage><lpage>64</lpage><pub-id pub-id-type="pmid">15504537</pub-id></element-citation></ref><ref id="B05"><label>5</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Alvar</surname><given-names>J</given-names></name><name><surname>Yactayo</surname><given-names>S</given-names></name><name><surname>Bern</surname><given-names>C</given-names></name></person-group><article-title>Leishmaniasis and poverty</article-title><source>Trends Parasitol</source><year>2006</year><volume>22</volume><fpage>552</fpage><lpage>557</lpage><pub-id pub-id-type="pmid">17023215</pub-id></element-citation></ref><ref id="B06"><label>6</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Alvar</surname><given-names>J</given-names></name><name><surname>Vélez</surname><given-names>ID</given-names></name><name><surname>Bern</surname><given-names>C</given-names></name><name><surname>Herrero</surname><given-names>M</given-names></name><name><surname>Desjeux</surname><given-names>P</given-names></name><name><surname>Cano</surname><given-names>J</given-names></name><etal></etal></person-group><article-title>Leishmaniasis worldwide and global estimates of its
incidence</article-title><source>PLoS One</source><year>2012</year><volume>7</volume><elocation-id></elocation-id></element-citation></ref><ref id="B07"><label>7</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Amaral</surname><given-names>VF</given-names></name><name><surname>Pirmez</surname><given-names>C</given-names></name><name><surname>Gonçalves</surname><given-names>AJS</given-names></name><name><surname>Ferreira</surname><given-names>V</given-names></name><name><surname>Grimaldi</surname><given-names>G</given-names><suffix>Jr</suffix></name></person-group><article-title>Cell populations in lesions of cutaneous leishmaniasis
of <italic>Leishmania (L.) amazonensis</italic>-infected Rhesus macaques,
<italic>Macaca mulata</italic></article-title><source>Mem Inst Oswaldo Cruz</source><year>2000</year><volume>95</volume><fpage>209</fpage><lpage>216</lpage><pub-id pub-id-type="pmid">10733740</pub-id></element-citation></ref><ref id="B08"><label>8</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Amaral</surname><given-names>VF</given-names></name><name><surname>Teva</surname><given-names>A</given-names></name><name><surname>Porrozzi</surname><given-names>R</given-names></name><name><surname>Silva</surname><given-names>AJ</given-names></name><name><surname>Pereira</surname><given-names>MS</given-names></name><name><surname>Oliveira-Neto</surname><given-names>MP</given-names></name><etal></etal></person-group><article-title><italic>Leishmania</italic> (<italic>Leishmania</italic>)
<italic>major</italic>-infected Rhesus macaques (<italic>Macaca mulatta</italic>)
develop varying levels of resistance against homologous
re-infections</article-title><source>Mem Inst Oswaldo Cruz</source><year>2001</year><volume>96</volume><fpage>795</fpage><lpage>804</lpage><pub-id pub-id-type="pmid">11562705</pub-id></element-citation></ref><ref id="B09"><label>9</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Banerjee</surname><given-names>R</given-names></name><name><surname>Kumar</surname><given-names>S</given-names></name><name><surname>Sen</surname><given-names>A</given-names></name><name><surname>Mookerjee</surname><given-names>A</given-names></name><name><surname>Roy</surname><given-names>S</given-names></name><name><surname>Pal</surname><given-names>S</given-names></name><etal></etal></person-group><article-title>TGF-β-regulated tyrosine phosphatases induce lymphocyte
apoptosis in <italic>Leishmania donovani</italic>-infected
hamsters</article-title><source>Immunol Cell Biol</source><year>2010</year><volume>89</volume><fpage>466</fpage><lpage>474</lpage><pub-id pub-id-type="pmid">20856262</pub-id></element-citation></ref><ref id="B10"><label>10</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Baneth</surname><given-names>G</given-names></name><name><surname>Koutinas</surname><given-names>AF</given-names></name><name><surname>Solano-Gallego</surname><given-names>L</given-names></name><name><surname>Bourdeau</surname><given-names>P</given-names></name><name><surname>Ferrer</surname><given-names>L</given-names></name></person-group><article-title>Canine leishmaniasis-new concepts and insights on an
expanding zoonosis: part one</article-title><source>Trends Parasitol</source><year>2008</year><volume>24</volume><fpage>324</fpage><lpage>330</lpage><pub-id pub-id-type="pmid">18514028</pub-id></element-citation></ref><ref id="B11"><label>11</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Barral-Netto</surname><given-names>M</given-names></name><name><surname>Barral</surname><given-names>A</given-names></name><name><surname>Brownell</surname><given-names>CE</given-names></name><name><surname>Skeiky</surname><given-names>YAW</given-names></name><name><surname>Ellingsworth</surname><given-names>LR</given-names></name><name><surname>Twardzik</surname><given-names>DR</given-names></name><etal></etal></person-group><article-title>Transforming growth factor-β in leishmanial infection: a
parasite escape mechanism</article-title><source>Science</source><year>1992</year><volume>257</volume><fpage>545</fpage><lpage>548</lpage><pub-id pub-id-type="pmid">1636092</pub-id></element-citation></ref><ref id="B12"><label>12</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Beattie</surname><given-names>L</given-names></name><name><surname>Peltan</surname><given-names>A</given-names></name><name><surname>Maroof</surname><given-names>A</given-names></name><name><surname>Kirby</surname><given-names>A</given-names></name><name><surname>Brown</surname><given-names>N</given-names></name><name><surname>Coles</surname><given-names>M</given-names></name><etal></etal></person-group><article-title>Dynamic imaging of experimental <italic>Leishmania
donovani</italic>-induced hepatic granulomas detects Kupffer cell-restricted
antigen presentation to antigen-specific CD8+ T cells</article-title><source>PLoS Pathog</source><year>2010</year><volume>6</volume><elocation-id></elocation-id></element-citation></ref><ref id="B13"><label>13</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Belkaid</surname><given-names>Y</given-names></name><name><surname>Kamhawi</surname><given-names>S</given-names></name><name><surname>Modi</surname><given-names>G</given-names></name><name><surname>Valenzuela</surname><given-names>J</given-names></name><name><surname>Noben-Trauth</surname><given-names>N</given-names></name><name><surname>Rowton</surname><given-names>E</given-names></name><etal></etal></person-group><article-title>Development of a natural model of cutaneous
leishmaniasis: powerful effects of vector saliva and saliva preexposure on the
long-term outcome of <italic>Leishmania major</italic> infection in the mouse ear
dermis</article-title><source>J Exp Med</source><year>1998</year><volume>188</volume><fpage>1941</fpage><lpage>1953</lpage><pub-id pub-id-type="pmid">9815271</pub-id></element-citation></ref><ref id="B14"><label>14</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bern</surname><given-names>C</given-names></name><name><surname>Maguire</surname><given-names>JH</given-names></name><name><surname>Alvar</surname><given-names>J</given-names></name></person-group><article-title>Complexities of assessing the disease burden
attributable to leishmaniasis</article-title><source>PLoS Negl Trop Dis</source><year>2008</year><volume>2</volume><elocation-id></elocation-id></element-citation></ref><ref id="B15"><label>15</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bezerril Andrade</surname><given-names>B</given-names></name><name><surname>Teixeira</surname><given-names>CR</given-names></name></person-group><article-title>Biomarkers for exposure to sand flies bites as tools to
aid control of leishmaniasis</article-title><source>Front Immunol</source><year>2012</year><volume>3</volume><fpage>121</fpage><lpage>127</lpage><pub-id pub-id-type="pmid">22661974</pub-id></element-citation></ref><ref id="B16"><label>16</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Blackwell</surname><given-names>JM</given-names></name><name><surname>Fakiola</surname><given-names>M</given-names></name><name><surname>Ibrahim</surname><given-names>ME</given-names></name><name><surname>Jamieson</surname><given-names>SE</given-names></name><name><surname>Jeronimo</surname><given-names>SB</given-names></name><name><surname>Miller</surname><given-names>EN</given-names></name><etal></etal></person-group><article-title>Genetics and visceral leishmaniasis: of mice and
man</article-title><source>Parasite Immunol</source><year>2009</year><volume>31</volume><fpage>254</fpage><lpage>266</lpage><pub-id pub-id-type="pmid">19388946</pub-id></element-citation></ref><ref id="B17"><label>17</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Blackwell</surname><given-names>JM</given-names></name><name><surname>Goswami</surname><given-names>T</given-names></name><name><surname>Evans</surname><given-names>CAW</given-names></name><name><surname>Sibthorpe</surname><given-names>D</given-names></name><name><surname>Papo</surname><given-names>N</given-names></name><name><surname>White</surname><given-names>JK</given-names></name><etal></etal></person-group><article-title>SLC11A1 (formely NRAMP1) and disease
resistance</article-title><source>Cell Microbiol</source><year>2011</year><volume>3</volume><fpage>773</fpage><lpage>784</lpage><pub-id pub-id-type="pmid">11736990</pub-id></element-citation></ref><ref id="B18"><label>18</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bogdan</surname><given-names>C</given-names></name><name><surname>Röllinghoff</surname><given-names>M</given-names></name></person-group><article-title>The immune response to <italic>Leishmania</italic>:
mechanisms of parasite control and evasion</article-title><source>Int J Parasitol</source><year>1998</year><volume>28</volume><fpage>121</fpage><lpage>134</lpage><pub-id pub-id-type="pmid">9504340</pub-id></element-citation></ref><ref id="B19"><label>19</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bourdoiseau</surname><given-names>G</given-names></name><name><surname>Bonnefont</surname><given-names>C</given-names></name><name><surname>Hoareau</surname><given-names>E</given-names></name><name><surname>Boehringer</surname><given-names>C</given-names></name><name><surname>Stolle</surname><given-names>T</given-names></name><name><surname>Chabanne</surname><given-names>L</given-names></name></person-group><article-title>Specific IgG1 and IgG2 antibody and lymphocyte subset
levels in naturally <italic>Leishmania infantum</italic> infected treated and
untreated dogs</article-title><source>Vet Immunol Immunopathol</source><year>1997</year><volume>59</volume><fpage>21</fpage><lpage>30</lpage><pub-id pub-id-type="pmid">9437823</pub-id></element-citation></ref><ref id="B20"><label>20</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Broderson</surname><given-names>JR</given-names></name><name><surname>Chapman</surname><given-names>WL</given-names><suffix>Jr</suffix></name><name><surname>Hanson</surname><given-names>WL</given-names></name></person-group><article-title>Experimental visceral leishmaniasis in the owl
monkey</article-title><source>Vet Pathol</source><year>1986</year><volume>23</volume><fpage>293</fpage><lpage>302</lpage><pub-id pub-id-type="pmid">3727315</pub-id></element-citation></ref><ref id="B21"><label>21</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Buxbaum</surname><given-names>LU</given-names></name><name><surname>Uzonna</surname><given-names>JE</given-names></name><name><surname>Goldschmidt</surname><given-names>MH</given-names></name><name><surname>Scott</surname><given-names>P</given-names></name></person-group><article-title>Control of New World cutaneous leishmaniasis is IL-12
independent but STAT4 dependent</article-title><source>Eur J Immunol</source><year>2002</year><volume>32</volume><fpage>3206</fpage><lpage>3212</lpage><pub-id pub-id-type="pmid">12555666</pub-id></element-citation></ref><ref id="B22"><label>22</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Canto-Lara</surname><given-names>SB</given-names></name><name><surname>Van Wynsberghe</surname><given-names>NR</given-names></name><name><surname>Vargas-Gonzalez</surname><given-names>A</given-names></name><name><surname>Ojeda-Farfán</surname><given-names>FF</given-names></name><name><surname>Andrade-Narváez</surname><given-names>FJ</given-names></name></person-group><article-title>Use of monoclonal antibodies for the identification of
<italic>Leishmania</italic> spp. from humans and wild rodents in the State of
Campeche, Mexico</article-title><source>Mem Inst Oswaldo Cruz</source><year>1999</year><volume>94</volume><fpage>305</fpage><lpage>309</lpage><pub-id pub-id-type="pmid">10348978</pub-id></element-citation></ref><ref id="B23"><label>23</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Carsillo</surname><given-names>M</given-names></name><name><surname>Kutala</surname><given-names>VK</given-names></name><name><surname>Puschel</surname><given-names>K</given-names></name><name><surname>Blaco</surname><given-names>J</given-names></name><name><surname>Kuppusamy</surname><given-names>P</given-names></name><name><surname>Niewiesk</surname><given-names>S</given-names></name></person-group><article-title>Nitric oxide production and nitric oxide synthase type
expression by cotton rat (<italic>Sigmodon hispidus</italic>) macrophages reflect
the same pattern as human macrophages</article-title><source>Dev Comp Immunol</source><year>2009</year><volume>33</volume><fpage>718</fpage><lpage>724</lpage><pub-id pub-id-type="pmid">19154756</pub-id></element-citation></ref><ref id="B24"><label>24</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chable-Santos</surname><given-names>JB</given-names></name><name><surname>Van Wynsberghe</surname><given-names>NR</given-names></name><name><surname>Canto-Lara</surname><given-names>SB</given-names></name><name><surname>Andrade-Narváez</surname><given-names>FJ</given-names></name></person-group><article-title>Isolation of <italic>Leishmania (Leishmania)
mexicana</italic> from wild rodents and their possible role in the transmission
of localized cutaneous leishmaniasis in the State of Campeche,
Mexico</article-title><source>Am J Trop Med Hyg</source><year>1995</year><volume>53</volume><fpage>141</fpage><lpage>145</lpage><pub-id pub-id-type="pmid">7677214</pub-id></element-citation></ref><ref id="B25"><label>25</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chamizo</surname><given-names>C</given-names></name><name><surname>Moreno</surname><given-names>J</given-names></name><name><surname>Alvar</surname><given-names>J</given-names></name></person-group><article-title>Semi-quantitative analysis of cytokine expression in
asymptomatic canine leishmaniasis</article-title><source>Vet Immunol Immunopathol</source><year>2005</year><volume>103</volume><fpage>67</fpage><lpage>75</lpage><pub-id pub-id-type="pmid">15626462</pub-id></element-citation></ref><ref id="B26"><label>26</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chang</surname><given-names>KP</given-names></name><name><surname>Dwyer</surname><given-names>DM</given-names></name></person-group><article-title>Hamster macrophage interactions <italic>in
vitro</italic>: cell entry, intracellular survival, and multiplication of
amastigotes</article-title><source>J Exp Med</source><year>1978</year><volume>147</volume><fpage>515</fpage><lpage>530</lpage><pub-id pub-id-type="pmid">564391</pub-id></element-citation></ref><ref id="B27"><label>27</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ciaramella</surname><given-names>P</given-names></name><name><surname>Oliva</surname><given-names>G</given-names></name><name><surname>Luna</surname><given-names>RD</given-names></name><name><surname>Gradoni</surname><given-names>L</given-names></name><name><surname>Ambrosio</surname><given-names>R</given-names></name><name><surname>Cortese</surname><given-names>L</given-names></name><etal></etal></person-group><article-title>A retrospective clinical study of canine leishmaniasis
in 150 dogs naturally infected by <italic>Leishmania infantum</italic></article-title><source>Vet Rec</source><year>1997</year><volume>141</volume><fpage>539</fpage><lpage>543</lpage><pub-id pub-id-type="pmid">9413121</pub-id></element-citation></ref><ref id="B28"><label>28</label><element-citation publication-type="book"><source>Control of the leishmaniasis: report of a meeting of the WHO Expert Committee
on the Control of Leishmaniases</source><publisher-loc>Geneva</publisher-loc><month>3</month><year>2010</year><series>(WHO technical report series no. 949)</series></element-citation></ref><ref id="B29"><label>29</label><element-citation publication-type="book"><person-group person-group-type="author"><name><surname>Cua Ake</surname><given-names>MA</given-names></name></person-group><article-title xml:lang="es">Infección subclínica en <italic>Peromyscus
yucatanicus</italic> inducida por el inóculo de 1×102 promastigotes de
<italic>Leishmania (Leishmania) mexican</italic></article-title><publisher-loc>Mérida</publisher-loc><publisher-name>Universidad Autónoma de Yucatán, Facultad de
Medicina</publisher-name><year>2008</year></element-citation></ref><ref id="B30"><label>30</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Dantas-Torres</surname><given-names>F</given-names></name></person-group><article-title>Canine leishmaniosis in South America</article-title><source>Parasit Vectors</source><year>2009</year><volume>2</volume><issue>Suppl 1</issue><fpage>S1</fpage><lpage>S1</lpage><pub-id pub-id-type="pmid">19426440</pub-id></element-citation></ref><ref id="B31"><label>31</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Almeida</surname><given-names>MC De</given-names></name><name><surname>Vilhena</surname><given-names>V</given-names></name><name><surname>Barral</surname><given-names>V</given-names></name><name><surname>Barral-Netto</surname><given-names>M</given-names></name></person-group><article-title>Leishmanial infection: analysis of its first steps. A
review</article-title><source xml:lang="pt">Mem Inst Oswaldo Cruz</source><year>2003</year><volume>98</volume><fpage>861</fpage><lpage>870</lpage><pub-id pub-id-type="pmid">14762510</pub-id></element-citation></ref><ref id="B32"><label>32</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Campos</surname><given-names>SN De</given-names></name><name><surname>Souza-Lemos</surname><given-names>C</given-names></name><name><surname>Teva</surname><given-names>A</given-names></name><name><surname>Porrozzi</surname><given-names>R</given-names></name><name><surname>Grimaldi</surname><given-names>G</given-names><suffix>Jr</suffix></name></person-group><article-title>Systemic and compartmentalised immune responses in a
<italic>Leishmania braziliensis</italic>-macaque model of self-healing
cutaneous leishmaniasis</article-title><source>Vet Immunol Immunopathol</source><year>2010</year><volume>137</volume><fpage>149</fpage><lpage>154</lpage><pub-id pub-id-type="pmid">20546932</pub-id></element-citation></ref><ref id="B33"><label>33</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lima</surname><given-names>H De</given-names></name><name><surname>Guglielmo</surname><given-names>Z De</given-names></name><name><surname>Rodríguez</surname><given-names>A</given-names></name><name><surname>Convit</surname><given-names>J</given-names></name><name><surname>Rodríguez</surname><given-names>N</given-names></name></person-group><article-title>Cotto rats (<italic>Sigmodon hispidus</italic>) and
black rats (<italic>Rattus rattus</italic>) as possible reservoirs of
<italic>Leishmani</italic>a spp. in Lara State, Venezuela</article-title><source>Mem Inst Oswaldo Cruz</source><year>2002</year><volume>97</volume><fpage>169</fpage><lpage>174</lpage><pub-id pub-id-type="pmid">12016437</pub-id></element-citation></ref><ref id="B34"><label>34</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Dennis</surname><given-names>VA</given-names></name><name><surname>Lujan</surname><given-names>R</given-names></name><name><surname>Chapman</surname><given-names>WL</given-names><suffix>Jr</suffix></name><name><surname>Hanson</surname><given-names>WL</given-names></name></person-group><article-title><italic>Leishmania donovani:</italic> cellular and humoral immune responses after
primary and challenge infections in squirrel monkeys, <italic>Saimiri
sciureus</italic></article-title><source>Exp Parasitol</source><year>1986</year><volume>61</volume><fpage>319</fpage><lpage>334</lpage><pub-id pub-id-type="pmid">2940111</pub-id></element-citation></ref><ref id="B35"><label>35</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Desjeux</surname><given-names>P</given-names></name></person-group><article-title>The increase in risk factors for leishmaniasis
worldwide</article-title><source>Trans R Soc Trop Med Hyg</source><year>2001</year><volume>95</volume><fpage>239</fpage><lpage>243</lpage><pub-id pub-id-type="pmid">11490989</pub-id></element-citation></ref><ref id="B36"><label>36</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Desjeux</surname><given-names>P</given-names></name></person-group><article-title>Leishmaniasis: current situation and new
perspectives</article-title><source>Comp Immunol Microbiol Infect Dis</source><year>2004</year><volume>27</volume><fpage>305</fpage><lpage>318</lpage><pub-id pub-id-type="pmid">15225981</pub-id></element-citation></ref><ref id="B37"><label>37</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Doherty</surname><given-names>TM</given-names></name><name><surname>Coffman</surname><given-names>RL</given-names></name></person-group><article-title><italic>Leishmania major</italic>: effect of infectious dose on T cell subset
development in BALB/c mice</article-title><source>Exp Parasitol</source><year>1996</year><volume>84</volume><fpage>124</fpage><lpage>135</lpage><pub-id pub-id-type="pmid">8932762</pub-id></element-citation></ref><ref id="B38"><label>38</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Dube</surname><given-names>A</given-names></name><name><surname>Sharma</surname><given-names>P</given-names></name><name><surname>Srivastava</surname><given-names>JK</given-names></name><name><surname>Misra</surname><given-names>A</given-names></name><name><surname>Naik</surname><given-names>S</given-names></name><name><surname>Katiyar</surname><given-names>JC</given-names></name></person-group><article-title>Vaccination of langur monkeys (<italic>Presbytis
entellus</italic>) against <italic>Leishmania donovani</italic> with autoclaved
<italic>L. major</italic> plus BCG</article-title><source>Parasitology</source><year>1998</year><volume>116</volume><fpage>219</fpage><lpage>221</lpage><pub-id pub-id-type="pmid">9550214</pub-id></element-citation></ref><ref id="B39"><label>39</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Engwerda</surname><given-names>CR</given-names></name><name><surname>Ato</surname><given-names>M</given-names></name><name><surname>Kaye</surname><given-names>PM</given-names></name></person-group><article-title>Macrophages, pathology and parasite persistence in
experimental visceral leishmaniasis</article-title><source>Trends Parasitol</source><year>2004</year><volume>20</volume><fpage>524</fpage><lpage>530</lpage><pub-id pub-id-type="pmid">15471704</pub-id></element-citation></ref><ref id="B40"><label>40</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Espitia</surname><given-names>CM</given-names></name><name><surname>Zhao</surname><given-names>W</given-names></name><name><surname>Saldarriaga</surname><given-names>O</given-names></name><name><surname>Osorio</surname><given-names>Y</given-names></name><name><surname>Harrison</surname><given-names>LM</given-names></name><name><surname>Cappello</surname><given-names>M</given-names></name><etal></etal></person-group><article-title>Duplex real-time reverse transcriptase PCR to determine
cytokine mRNA expression in a hamster model of New World cutaneous
leishmaniasis</article-title><source>BMC Immunol</source><year>2010</year><volume>11</volume><fpage>31</fpage><lpage>42</lpage><pub-id pub-id-type="pmid">20569429</pub-id></element-citation></ref><ref id="B41"><label>41</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Fazzani</surname><given-names>C</given-names></name><name><surname>Guedes</surname><given-names>PA</given-names></name><name><surname>Sena</surname><given-names>A</given-names></name><name><surname>Souza</surname><given-names>EB</given-names></name><name><surname>Goto</surname><given-names>H</given-names></name><name><surname>Lindoso</surname><given-names>JAL</given-names></name></person-group><article-title>Dynamics of immunosuppression in hamsters with
experimental visceral leishmaniasis</article-title><source>Braz J Med Biol Res</source><year>2011</year><volume>44</volume><fpage>666</fpage><lpage>670</lpage><pub-id pub-id-type="pmid">21584442</pub-id></element-citation></ref><ref id="B42"><label>42</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gantt</surname><given-names>KR</given-names></name><name><surname>Goldman</surname><given-names>TL</given-names></name><name><surname>McCormick</surname><given-names>ML</given-names></name><name><surname>Miller</surname><given-names>MA</given-names></name><name><surname>Jeronimo</surname><given-names>SMB</given-names></name><name><surname>Nascimento</surname><given-names>ET</given-names></name><etal></etal></person-group><article-title>Oxidative responses of human and murine macrophages
during phagocytosis of <italic>Leishmania chagasi</italic></article-title><source>J Immunol</source><year>2001</year><volume>167</volume><fpage>893</fpage><lpage>901</lpage><pub-id pub-id-type="pmid">11441096</pub-id></element-citation></ref><ref id="B43"><label>43</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gicheru</surname><given-names>MM</given-names></name><name><surname>Olobo</surname><given-names>JO</given-names></name><name><surname>Kariuki</surname><given-names>TM</given-names></name><name><surname>Adhiambo</surname><given-names>C</given-names></name></person-group><article-title>Visceral leishmaniasis in ververt monkeys: immunological
responses during asymptomatic infections</article-title><source>Scand J Immunol</source><year>1995</year><volume>41</volume><fpage>202</fpage><lpage>208</lpage><pub-id pub-id-type="pmid">7863267</pub-id></element-citation></ref><ref id="B44"><label>44</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gomes</surname><given-names>R</given-names></name><name><surname>Teixeira</surname><given-names>C</given-names></name><name><surname>Texeira</surname><given-names>MJ</given-names></name><name><surname>Oliveira</surname><given-names>F</given-names></name><name><surname>Menezes</surname><given-names>MJ</given-names></name><name><surname>Silva</surname><given-names>C</given-names></name><etal></etal></person-group><article-title>Immunity to a salivary protein of a sand fly vector
protects against the fatal outcome of visceral leishmaniasis in a hamster
model</article-title><source>Proc Natl Acad Sci USA</source><year>2008</year><volume>105</volume><fpage>7845</fpage><lpage>7850</lpage><pub-id pub-id-type="pmid">18509051</pub-id></element-citation></ref><ref id="B45"><label>45</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Goto</surname><given-names>H</given-names></name><name><surname>Prianti</surname><given-names>MG</given-names></name></person-group><article-title>Immunoactivation and immunopathogeny during active
visceral leishmaniasis</article-title><source>Rev Inst Med Trop Sao Paulo</source><year>2009</year><volume>51</volume><fpage>241</fpage><lpage>246</lpage><pub-id pub-id-type="pmid">19893975</pub-id></element-citation></ref><ref id="B46"><label>46</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Grimaldi</surname><given-names>G</given-names><suffix>Jr</suffix></name></person-group><article-title>The utility of rhesus monkey (<italic>Macaca
mulatta</italic>) and non-human primate models for preclinical testing of
<italic>Leishmania</italic> candidate vaccines</article-title><source>Mem Inst Oswaldo Cruz</source><year>2008</year><volume>103</volume><fpage>629</fpage><lpage>644</lpage><pub-id pub-id-type="pmid">19057811</pub-id></element-citation></ref><ref id="B47"><label>47</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Guénet</surname><given-names>JL</given-names></name><name><surname>Bonhomme</surname><given-names>F</given-names></name></person-group><article-title>Wild mice: an ever-increasing contribution to a popular
mammalian model</article-title><source>Trends Genet</source><year>2003</year><volume>19</volume><fpage>24</fpage><lpage>31</lpage><pub-id pub-id-type="pmid">12493245</pub-id></element-citation></ref><ref id="B48"><label>48</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gupta</surname><given-names>S</given-names></name><collab>Nishi</collab></person-group><article-title>Visceral leishmaniasis: experimental models for drug
discovery</article-title><source>Indian J Med Res</source><year>2011</year><volume>133</volume><fpage>27</fpage><lpage>39</lpage><pub-id pub-id-type="pmid">21321417</pub-id></element-citation></ref><ref id="B49"><label>49</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Handman</surname><given-names>E</given-names></name></person-group><article-title>Leishmaniasis: current status of vaccine
development</article-title><source>Clin Microbiol Rev</source><year>2001</year><volume>14</volume><fpage>229</fpage><lpage>243</lpage><pub-id pub-id-type="pmid">11292637</pub-id></element-citation></ref><ref id="B50"><label>50</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hommel</surname><given-names>M</given-names></name><name><surname>Jaffe</surname><given-names>CL</given-names></name><name><surname>Travi</surname><given-names>B</given-names></name><name><surname>Milon</surname><given-names>G</given-names></name></person-group><article-title>Experimental models for leishmaniasis and for testing
anti-leishmanial vaccines</article-title><source>Ann Trop Med Parasitol</source><year>2005</year><volume>89</volume><issue>Suppl 1</issue><fpage>55</fpage><lpage>73</lpage><pub-id pub-id-type="pmid">8745928</pub-id></element-citation></ref><ref id="B51"><label>51</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hotez</surname><given-names>PJ</given-names></name><name><surname>Remme</surname><given-names>JH</given-names></name><name><surname>Buss</surname><given-names>P</given-names></name><name><surname>Alleyne</surname><given-names>G</given-names></name><name><surname>Morel</surname><given-names>C</given-names></name><name><surname>Breman</surname><given-names>JG</given-names></name></person-group><article-title>Combating tropical infectious diseases: report of the
Disease Control Priorities in Developing Countries Project</article-title><source>Clin Infect Dis</source><year>2004</year><volume>38</volume><fpage>871</fpage><lpage>878</lpage><pub-id pub-id-type="pmid">14999633</pub-id></element-citation></ref><ref id="B52"><label>52</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hotez</surname><given-names>PJ</given-names></name><name><surname>Molyneux</surname><given-names>DH</given-names></name><name><surname>Fenwick</surname><given-names>A</given-names></name><name><surname>Ottesen</surname><given-names>E</given-names></name><name><surname>Ehrlich Sachs</surname><given-names>S</given-names></name><name><surname>Sachs</surname><given-names>JD</given-names></name></person-group><article-title>Incorporating a rapid-impact package for neglected
tropical diseases with programs for HIV/AIDS, tuberculosis, and
malaria</article-title><source>PLoS Med</source><year>2006</year><volume>3</volume><elocation-id></elocation-id></element-citation></ref><ref id="B53"><label>53</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jones</surname><given-names>DE</given-names></name><name><surname>Ackermann</surname><given-names>MR</given-names></name><name><surname>Wille</surname><given-names>U</given-names></name><name><surname>Hunter</surname><given-names>CA</given-names></name><name><surname>Scott</surname><given-names>P</given-names></name></person-group><article-title>Early enhanced Th1 response after <italic>Leishmania
amazonensis</italic> infection of C57BL/6 interleukin-10-deficient mice does
not lead to resolution of infection</article-title><source>Infect Immun</source><year>2002</year><volume>70</volume><fpage>2151</fpage><lpage>2158</lpage><pub-id pub-id-type="pmid">11895981</pub-id></element-citation></ref><ref id="B54"><label>54</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jones</surname><given-names>DE</given-names></name><name><surname>Buxbaum</surname><given-names>LU</given-names></name><name><surname>Scott</surname><given-names>P</given-names></name></person-group><article-title>IL-4-independent inhibition of IL-12 responsiveness
during <italic>Leishmania amazonensis</italic> infection</article-title><source>J Immunol</source><year>2000</year><volume>165</volume><fpage>364</fpage><lpage>372</lpage><pub-id pub-id-type="pmid">10861073</pub-id></element-citation></ref><ref id="B55"><label>55</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kedzierski</surname><given-names>L</given-names></name></person-group><article-title>Leishmaniasis vaccine: where are we
today?</article-title><source>J Glob Infect Dis</source><year>2012</year><volume>2</volume><fpage>177</fpage><lpage>85</lpage><pub-id pub-id-type="pmid">20606974</pub-id></element-citation></ref><ref id="B56"><label>56</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kenney</surname><given-names>RT</given-names></name><name><surname>Sacks</surname><given-names>DL</given-names></name><name><surname>Sypek</surname><given-names>JP</given-names></name><name><surname>Vilela</surname><given-names>L</given-names></name><name><surname>Gam</surname><given-names>AA</given-names></name><name><surname>Evans-Davis</surname><given-names>K</given-names></name></person-group><article-title>Protective immunity using recombinant human IL-12 and
alum as adjuvants in a primate model of cutaneous leishmaniasis</article-title><source>J Immunol</source><year>1999</year><volume>163</volume><fpage>4481</fpage><lpage>4488</lpage><pub-id pub-id-type="pmid">10510390</pub-id></element-citation></ref><ref id="B57"><label>57</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kimblin</surname><given-names>N</given-names></name><name><surname>Peters</surname><given-names>N</given-names></name><name><surname>Debrabant</surname><given-names>A</given-names></name><name><surname>Secundino</surname><given-names>N</given-names></name><name><surname>Egen</surname><given-names>J</given-names></name><name><surname>Lawyer</surname><given-names>P</given-names></name><etal></etal></person-group><article-title>Quantification of the infectious dose of
<italic>Leishmania major</italic> transmitted to the skin by single sand
flies</article-title><source>Proc Natl Acad Sci USA</source><year>2008</year><volume>105</volume><fpage>125</fpage><lpage>130</lpage></element-citation></ref><ref id="B58"><label>58</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kumar</surname><given-names>R</given-names></name><name><surname>Nylén</surname><given-names>S</given-names></name></person-group><article-title>Immunobiology of visceral leishmaniasis</article-title><source>Front Immunol</source><year>2012</year><volume>3</volume><fpage>251</fpage><lpage>251</lpage><pub-id pub-id-type="pmid">22912637</pub-id></element-citation></ref><ref id="B59"><label>59</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lage</surname><given-names>RS</given-names></name><name><surname>Oliveira</surname><given-names>GC</given-names></name><name><surname>Busek</surname><given-names>SU</given-names></name><name><surname>Guerra</surname><given-names>LL</given-names></name><name><surname>Giunchetti</surname><given-names>RC</given-names></name><name><surname>Corrêa-Oliveira</surname><given-names>R</given-names></name><etal></etal></person-group><article-title>Analysis of the cytokine profile in spleen cells from
dogs naturally infected by <italic>Leishmania chagasi</italic></article-title><source>Vet Immunol Immunopathol</source><year>2007</year><volume>115</volume><fpage>135</fpage><lpage>145</lpage><pub-id pub-id-type="pmid">17097741</pub-id></element-citation></ref><ref id="B60"><label>60</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lang</surname><given-names>T</given-names></name><name><surname>Courret</surname><given-names>N</given-names></name><name><surname>Colle</surname><given-names>JH</given-names></name><name><surname>Milon</surname><given-names>G</given-names></name><name><surname>Antoine</surname><given-names>JC</given-names></name></person-group><article-title>The levels and patterns of cytokines produced by CD4 T
lymphocytes of BALB/c mice infected with <italic>Leishmania major</italic> by
inoculation into the ear dermis depend on the infectiousness and size of the
inoculums</article-title><source>Infect Immun</source><year>2003</year><volume>71</volume><fpage>2674</fpage><lpage>2683</lpage><pub-id pub-id-type="pmid">12704142</pub-id></element-citation></ref><ref id="B61"><label>61</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Liew</surname><given-names>FY</given-names></name><name><surname>Wei</surname><given-names>X</given-names></name><name><surname>Proudfoot</surname><given-names>L</given-names></name></person-group><article-title>Cytokines and nitric oxide as effector molecules against
parasitic infections</article-title><source>Philos Trans R Soc Lond B Biol Sci</source><year>1997</year><volume>352</volume><fpage>1311</fpage><lpage>1315</lpage><pub-id pub-id-type="pmid">9355122</pub-id></element-citation></ref><ref id="B62"><label>62</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lima</surname><given-names>CH</given-names></name><name><surname>Titus</surname><given-names>RG</given-names></name></person-group><article-title>Effects of sand fly vector saliva on development of
cutaneous lesions and the immune response to <italic>Leishmania
braziliensis</italic> in BALB/c mice</article-title><source>Infect Immun</source><year>1996</year><volume>64</volume><fpage>5442</fpage><lpage>5445</lpage><pub-id pub-id-type="pmid">8945606</pub-id></element-citation></ref><ref id="B63"><label>63</label><element-citation publication-type="book"><person-group person-group-type="author"><name><surname>Loría Cervera</surname><given-names>EN</given-names></name></person-group><source>Implementación de técnicas moleculares para el análisis de
citocinas Th1 (Interleucina-12, interferón gamma y factor de necrosis tumoral
alfa) de <italic>Peromyscus yucatanicus</italic></source><publisher-loc>Mérida</publisher-loc><publisher-name>Universidad Autónoma de Yucatán</publisher-name><year>2011</year></element-citation></ref><ref id="B64"><label>64</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Loría-Cervera</surname><given-names>EN</given-names></name><name><surname>Sosa-Bibiano</surname><given-names>EI</given-names></name><name><surname>Villanueva-Lizama</surname><given-names>LE</given-names></name><name><surname>Van Wynsberghe</surname><given-names>NR</given-names></name><name><surname>Canto-Lara</surname><given-names>SB</given-names></name><name><surname>Batún-Cutz</surname><given-names>JL</given-names></name><etal></etal></person-group><article-title>Nitric oxide production by <italic>Peromyscus
yucatanicus</italic> (Rodentia) infected with <italic>Leishmania (Leishmania)
mexicana</italic></article-title><source>Mem Inst Oswaldo Cruz</source><year>2013</year><volume>108</volume><fpage>172</fpage><lpage>177</lpage><pub-id pub-id-type="pmid">23579796</pub-id></element-citation></ref><ref id="B65"><label>65</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Maüel</surname><given-names>J</given-names></name></person-group><article-title>Macrophage-parasite interactions in
<italic>Leishmania</italic> infections</article-title><source>J Leukoc Biol</source><year>1990</year><volume>47</volume><fpage>187</fpage><lpage>193</lpage><pub-id pub-id-type="pmid">2406358</pub-id></element-citation></ref><ref id="B66"><label>66</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>McMahon-Pratt</surname><given-names>D</given-names></name><name><surname>Alexander</surname><given-names>J</given-names></name></person-group><article-title>Does the <italic>Leishmania major</italic> paradigm of
pathogenesis and protection hold for New World cutaneos leishmaniases or the
visceral disease?</article-title><source>Immunol Rev</source><year>2004</year><volume>201</volume><fpage>206</fpage><lpage>224</lpage><pub-id pub-id-type="pmid">15361243</pub-id></element-citation></ref><ref id="B67"><label>67</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Melby</surname><given-names>P</given-names></name><name><surname>Tryon</surname><given-names>V</given-names></name><name><surname>Chandrasekar</surname><given-names>V</given-names></name><name><surname>Freeman</surname><given-names>GL</given-names></name></person-group><article-title>Cloning of Syrian hamster (<italic>Mesocricetus
auratus</italic>) cytokine cDNAs and analysis of cytokine mRNA expression in
experimental visceral leishmaniasis</article-title><source>Infect Immun</source><year>1998</year><volume>66</volume><fpage>2135</fpage><lpage>2142</lpage><pub-id pub-id-type="pmid">9573100</pub-id></element-citation></ref><ref id="B68"><label>68</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Melby</surname><given-names>PC</given-names></name><name><surname>Chandrasekar</surname><given-names>B</given-names></name><name><surname>Zhao</surname><given-names>W</given-names></name><name><surname>Coe</surname><given-names>JE</given-names></name></person-group><article-title>The hamster as a model of human visceral leishmaniasis:
progressive disease and impaired generation of nitric oxide in the face of a
prominent Th1-like cytokine response</article-title><source>J Immunol</source><year>2001</year><volume>166</volume><fpage>1912</fpage><lpage>1920</lpage><pub-id pub-id-type="pmid">11160239</pub-id></element-citation></ref><ref id="B69"><label>69</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Menezes-Sousa</surname><given-names>D</given-names></name><name><surname>Corrêa-Oliveira</surname><given-names>R</given-names></name><name><surname>Guerra-Sá</surname><given-names>R</given-names></name><name><surname>Giunchetti</surname><given-names>RC</given-names></name><name><surname>Texeira-Carvalho</surname><given-names>A</given-names></name><name><surname>Martins-Filho</surname><given-names>OA</given-names></name><etal></etal></person-group><article-title>Cytokine and transcription factor profiles in the skin
of dogs naturally infected by <italic>Leishmania (Leishmania) chagasi</italic>presenting distinct cutaneous parasite density and clinical status</article-title><source>Vet Parasitol</source><year>2011</year><volume>177</volume><fpage>39</fpage><lpage>49</lpage><pub-id pub-id-type="pmid">21163578</pub-id></element-citation></ref><ref id="B70"><label>70</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Menon</surname><given-names>J</given-names></name><name><surname>Bretscher</surname><given-names>P</given-names></name></person-group><article-title>Parasite dose determines the Th1 / Th2 nature of the
response <italic>Leishmania major</italic> independently of infection route and
strain of host or parasite</article-title><source>Eur J Immunol</source><year>1998</year><volume>28</volume><fpage>4020</fpage><lpage>4028</lpage><pub-id pub-id-type="pmid">9862338</pub-id></element-citation></ref><ref id="B71"><label>71</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Misra</surname><given-names>A</given-names></name><name><surname>Dube</surname><given-names>A</given-names></name><name><surname>Srivastava</surname><given-names>B</given-names></name><name><surname>Sharma</surname><given-names>P</given-names></name><name><surname>Srivastava</surname><given-names>JK</given-names></name><name><surname>Katiyar</surname><given-names>JC</given-names></name><etal></etal></person-group><article-title>Successful vaccination against <italic>Leishmania
donovani</italic> infection in Indian langur using alum-precipitated autoclaved
<italic>Leishmania major</italic> with BCG</article-title><source>Vaccine</source><year>2001</year><volume>19</volume><fpage>3485</fpage><lpage>3492</lpage><pub-id pub-id-type="pmid">11348715</pub-id></element-citation></ref><ref id="B72"><label>72</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mookerjee</surname><given-names>A</given-names></name><name><surname>Sen</surname><given-names>PC</given-names></name><name><surname>Ghose</surname><given-names>AC</given-names></name></person-group><article-title>Immunosuppression in hamsters with progressive visceral
leishmaniasis is associated with an impairment of protein kinase C activity in
their lymphocytes that can be partially reversed by okadaic acid or
anti-transforming growth factor β antibody</article-title><source>Infect Immun</source><year>2003</year><volume>71</volume><fpage>2439</fpage><lpage>2446</lpage><pub-id pub-id-type="pmid">12704114</pub-id></element-citation></ref><ref id="B73"><label>73</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Moura</surname><given-names>TR</given-names></name><name><surname>Novais</surname><given-names>FO</given-names></name><name><surname>Oliveira</surname><given-names>F</given-names></name><name><surname>Clarêncio</surname><given-names>J</given-names></name><name><surname>Noronha</surname><given-names>A</given-names></name><name><surname>Barral</surname><given-names>A</given-names></name><etal></etal></person-group><article-title>Toward a novel experimental model of infection to study
American cutaneous leishmaniasis caused by <italic>Leishmania
braziliensis</italic></article-title><source>Infect Immun</source><year>2005</year><volume>73</volume><fpage>5827</fpage><lpage>5834</lpage><pub-id pub-id-type="pmid">16113301</pub-id></element-citation></ref><ref id="B74"><label>74</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mukbel</surname><given-names>RM</given-names></name><name><surname>Patten</surname><given-names>C</given-names><suffix>Jr</suffix></name><name><surname>Gibson</surname><given-names>K</given-names></name><name><surname>Ghosh</surname><given-names>M</given-names></name><name><surname>Petersen</surname><given-names>C</given-names></name><name><surname>Jones</surname><given-names>DE</given-names></name></person-group><article-title>Macrophage killing of <italic>Leishmania
amazonensis</italic> amastigotes requires both nitric oxide and
superoxide</article-title><source>Am J Trop Med Hyg</source><year>2007</year><volume>76</volume><fpage>669</fpage><lpage>675</lpage><pub-id pub-id-type="pmid">17426168</pub-id></element-citation></ref><ref id="B75"><label>75</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Murray</surname><given-names>HW</given-names></name><name><surname>Masur</surname><given-names>H</given-names></name><name><surname>Keithly</surname><given-names>JS</given-names></name></person-group><article-title>Cell mediated immune response in experimental visceral
leishmaniasis. I. Correlation between resistance to <italic>L. donovani</italic>and lymphokine-generating capacity</article-title><source>J Immunol</source><year>1982</year><volume>129</volume><fpage>344</fpage><lpage>350</lpage><pub-id pub-id-type="pmid">7086136</pub-id></element-citation></ref><ref id="B76"><label>76</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Murray</surname><given-names>HW</given-names></name><name><surname>Stem</surname><given-names>JJ</given-names></name><name><surname>Welte</surname><given-names>K</given-names></name><name><surname>Rubin</surname><given-names>BY</given-names></name><name><surname>Carreiro</surname><given-names>SM</given-names></name><name><surname>Nathan</surname><given-names>CF</given-names></name></person-group><article-title>Experimental visceral leishmaniasis: production of
interleukin 2 and interferon-gamma, tissue reaction and response to treatment with
interleukin 2 and interferon-gamma</article-title><source>J Immunol</source><year>1987</year><volume>138</volume><fpage>2290</fpage><lpage>2297</lpage><pub-id pub-id-type="pmid">3104456</pub-id></element-citation></ref><ref id="B77"><label>77</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Murray</surname><given-names>HW</given-names></name><name><surname>Delph-Etienne</surname><given-names>S</given-names></name></person-group><article-title>Roles of endogenous gamma interferon and macrophage
microbicidal mechanisms in host response to chemotherapy in experimental visceral
leishmaniasis</article-title><source>Infect Immun</source><year>2000</year><volume>68</volume><fpage>288</fpage><lpage>293</lpage><pub-id pub-id-type="pmid">10603400</pub-id></element-citation></ref><ref id="B78"><label>78</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Murray</surname><given-names>HW</given-names></name><name><surname>Berman</surname><given-names>JD</given-names></name><name><surname>Davies</surname><given-names>CR</given-names></name><name><surname>Saravia</surname><given-names>NG</given-names></name></person-group><article-title>Advances in leishmaniasis</article-title><source>Lancet</source><year>2005</year><volume>366</volume><fpage>1561</fpage><lpage>1577</lpage><pub-id pub-id-type="pmid">16257344</pub-id></element-citation></ref><ref id="B79"><label>79</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nickol</surname><given-names>AD</given-names></name><name><surname>Bonventre</surname><given-names>PF</given-names></name></person-group><article-title>Immunosuppression associated with visceral leishmaniasis
of hamsters</article-title><source>Parasite Immunol</source><year>1985</year><volume>7</volume><fpage>439</fpage><lpage>449</lpage><pub-id pub-id-type="pmid">4034238</pub-id></element-citation></ref><ref id="B80"><label>80</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Niewiesk</surname><given-names>S</given-names></name><name><surname>Prince</surname><given-names>G</given-names></name></person-group><article-title>Diversifying animal models: the use of hispid cotton
rats (<italic>Sigmodon hispidus</italic>) in infectious diseases</article-title><source>Lab Anim</source><year>2002</year><volume>36</volume><fpage>357</fpage><lpage>372</lpage><pub-id pub-id-type="pmid">12396279</pub-id></element-citation></ref><ref id="B81"><label>81</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Norsworthy</surname><given-names>NB</given-names></name><name><surname>Sun</surname><given-names>J</given-names></name><name><surname>Elnaiem</surname><given-names>D</given-names></name><name><surname>Lanzaro</surname><given-names>G</given-names></name><name><surname>Soong</surname><given-names>L</given-names></name></person-group><article-title>Sand fly saliva enhances <italic>Leishmania
amazonensis</italic> infection by modulating interleukin-10
production</article-title><source>Infect Immun</source><year>2004</year><volume>72</volume><fpage>1240</fpage><lpage>1247</lpage><pub-id pub-id-type="pmid">14977924</pub-id></element-citation></ref><ref id="B82"><label>82</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Panaro</surname><given-names>MA</given-names></name><name><surname>Acquafredda</surname><given-names>A</given-names></name><name><surname>Lisi</surname><given-names>S</given-names></name><name><surname>Lofrumento</surname><given-names>DD</given-names></name><name><surname>Mitolo</surname><given-names>V</given-names></name><name><surname>Sisto</surname><given-names>M</given-names></name><etal></etal></person-group><article-title>Nitric oxide production by macrophages of dogs
vaccinated with killed <italic>Leishmania infantum</italic>promastigotes</article-title><source>Comp Immunol Microbiol Infect Dis</source><year>2001</year><volume>24</volume><fpage>187</fpage><lpage>195</lpage><pub-id pub-id-type="pmid">11440191</pub-id></element-citation></ref><ref id="B83"><label>83</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Panaro</surname><given-names>MA</given-names></name><name><surname>Brandonisio</surname><given-names>O</given-names></name><name><surname>Caprerii</surname><given-names>D</given-names></name><name><surname>Cavallo</surname><given-names>P</given-names></name><name><surname>Cianciulli</surname><given-names>A</given-names></name><name><surname>Mitolo</surname><given-names>V</given-names></name><etal></etal></person-group><article-title>Canine leishmaniasis in Southern Italy: a role for
nitric oxide released from activated macrophages in asymptomatic
infection?</article-title><source>Parasite Vectors</source><year>2008</year><volume>1</volume><fpage>10</fpage><lpage>17</lpage></element-citation></ref><ref id="B84"><label>84</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Perez</surname><given-names>LE</given-names></name><name><surname>Chandrasekar</surname><given-names>B</given-names></name><name><surname>Saldarriaga</surname><given-names>OA</given-names></name><name><surname>Zhao</surname><given-names>W</given-names></name><name><surname>Arteaga</surname><given-names>LT</given-names></name><name><surname>Travi</surname><given-names>BL</given-names></name><etal></etal></person-group><article-title>Reduced nitric oxide synthase 2 (NOS2) promoter activity
in the Syrian hamster renders the animal functionally deficient in NOS2 activity
and unable to control an intracellular pathogen</article-title><source>J Immunol</source><year>2006</year><volume>176</volume><fpage>5519</fpage><lpage>5528</lpage><pub-id pub-id-type="pmid">16622021</pub-id></element-citation></ref><ref id="B85"><label>85</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Pinelli</surname><given-names>E</given-names></name><name><surname>Killick-Kendrick</surname><given-names>R</given-names></name><name><surname>Wagenaar</surname><given-names>J</given-names></name><name><surname>Bernardina</surname><given-names>W</given-names></name><name><surname>Del Real</surname><given-names>G</given-names></name><name><surname>Ruitenberg</surname><given-names>J</given-names></name></person-group><article-title>Cellular and humoral immune responses in dogs
experimentally and naturally infected with <italic>Leishmania infantum</italic></article-title><source>Infect Immun</source><year>1994</year><volume>62</volume><fpage>229</fpage><lpage>235</lpage><pub-id pub-id-type="pmid">8262632</pub-id></element-citation></ref><ref id="B86"><label>86</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Pinelli</surname><given-names>E</given-names></name><name><surname>Gonzalo</surname><given-names>RM</given-names></name><name><surname>Boog</surname><given-names>CJP</given-names></name><name><surname>Rutten</surname><given-names>V</given-names></name><name><surname>Gebhard</surname><given-names>D</given-names></name><name><surname>Del Real</surname><given-names>G</given-names></name><etal></etal></person-group><article-title><italic>Leishmania infantum</italic> specific T cell lines derived from
asymptomatic dogs that lyse infected macrophages in a major histocompatibility
complex restricted manner</article-title><source>Eur J Immunol</source><year>1995</year><volume>25</volume><fpage>1594</fpage><lpage>1600</lpage><pub-id pub-id-type="pmid">7614987</pub-id></element-citation></ref><ref id="B87"><label>87</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Pinelli</surname><given-names>E</given-names></name><name><surname>van der Kaaij</surname><given-names>SY</given-names></name><name><surname>Slappendel</surname><given-names>R</given-names></name><name><surname>Fragio</surname><given-names>C</given-names></name><name><surname>Ruitenberg</surname><given-names>EJ</given-names></name><name><surname>Bernadina</surname><given-names>W</given-names></name><etal></etal></person-group><article-title>Detection of canine cytokine gene expression by reverse
transcription-polymerase chain reaction</article-title><source>Vet Immunol Immunopathol</source><year>1999</year><volume>69</volume><fpage>121</fpage><lpage>126</lpage><pub-id pub-id-type="pmid">10507299</pub-id></element-citation></ref><ref id="B88"><label>88</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Pinelli</surname><given-names>E</given-names></name><name><surname>Gebhard</surname><given-names>D</given-names></name><name><surname>Mommaas</surname><given-names>AM</given-names></name><name><surname>van Hoeij</surname><given-names>M</given-names></name><name><surname>Langermans</surname><given-names>J</given-names></name><name><surname>Ruitenberg</surname><given-names>EJ</given-names></name><etal></etal></person-group><article-title>Infection of a canine macrophage cell line with
<italic>Leishmania infantum</italic>: determination of nitric oxide production
and anti-leishmanial activity</article-title><source>Vet Parasitol</source><year>2000</year><volume>92</volume><fpage>181</fpage><lpage>189</lpage><pub-id pub-id-type="pmid">10962155</pub-id></element-citation></ref><ref id="B89"><label>89</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Pinheiro</surname><given-names>PHC</given-names></name><name><surname>Dias</surname><given-names>SS</given-names></name><name><surname>Eulálio</surname><given-names>KD</given-names></name><name><surname>Mendonça</surname><given-names>IL</given-names></name><name><surname>Katz</surname><given-names>S</given-names></name><name><surname>Barbiéri</surname><given-names>CL</given-names></name></person-group><article-title>Recombinant cysteine proteinase from <italic>Leishmania
(Leishmania) chagasi</italic> implicated in human and dog T-cell
responses</article-title><source>Infect Immun</source><year>2005</year><volume>73</volume><fpage>3787</fpage><lpage>2789</lpage><pub-id pub-id-type="pmid">15908413</pub-id></element-citation></ref><ref id="B90"><label>90</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Quinnell</surname><given-names>RJ</given-names></name><name><surname>Courtenay</surname><given-names>O</given-names></name><name><surname>Shaw</surname><given-names>MA</given-names></name><name><surname>Day</surname><given-names>MJ</given-names></name><name><surname>Garcez</surname><given-names>LM</given-names></name><name><surname>Dye</surname><given-names>C</given-names></name><etal></etal></person-group><article-title>Tissue cytokine responses in canine visceral
leishmaniasis</article-title><source>J Infect Dis</source><year>2001</year><volume>183</volume><fpage>1421</fpage><lpage>1424</lpage><pub-id pub-id-type="pmid">11294678</pub-id></element-citation></ref><ref id="B91"><label>91</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Randolph</surname><given-names>SE</given-names></name></person-group><article-title>To what extent has climate change contributed to the
recent epidemiology of tick-borne diseases?</article-title><source>Vet Parasitol</source><year>2010</year><volume>167</volume><fpage>92</fpage><lpage>94</lpage><pub-id pub-id-type="pmid">19833440</pub-id></element-citation></ref><ref id="B92"><label>92</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Reithinger</surname><given-names>R</given-names></name><name><surname>Davies</surname><given-names>CR</given-names></name></person-group><article-title>Is the domestic dog (C<italic>anis familiaris</italic>)
a reservoir host of American cutaneous leishmaniasis? A critical review of the
current evidence</article-title><source>Am J Trop Med Hyg</source><year>1999</year><volume>61</volume><fpage>530</fpage><lpage>541</lpage><pub-id pub-id-type="pmid">10548285</pub-id></element-citation></ref><ref id="B93"><label>93</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Remme</surname><given-names>JHF</given-names></name><name><surname>Blas</surname><given-names>E</given-names></name><name><surname>Chistulo</surname><given-names>L</given-names></name><name><surname>Desjeux</surname><given-names>PM</given-names></name><name><surname>Engers</surname><given-names>HD</given-names></name><name><surname>Kanyok</surname><given-names>TP</given-names></name><etal></etal></person-group><article-title>Strategic emphases for tropical diseases research: a TDR
perspective</article-title><source>Trends Parasitol</source><year>2002</year><volume>18</volume><fpage>421</fpage><lpage>426</lpage><pub-id pub-id-type="pmid">12377584</pub-id></element-citation></ref><ref id="B94"><label>94</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Roberts</surname><given-names>M</given-names></name><name><surname>Stober</surname><given-names>C</given-names></name><name><surname>Mckenzie</surname><given-names>A</given-names></name><name><surname>Blackwell</surname><given-names>J</given-names></name></person-group><article-title>Interleukin-4 (IL-4) and IL-10 collude in vaccine
failure for novel exacerbatory antigens in murine <italic>Leishmania
major</italic> infection</article-title><source>Infect Immun</source><year>2005</year><volume>73</volume><fpage>7620</fpage><lpage>7628</lpage><pub-id pub-id-type="pmid">16239566</pub-id></element-citation></ref><ref id="B95"><label>95</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rodrigues Júnior</surname><given-names>V</given-names></name><name><surname>Silva</surname><given-names>JS Da</given-names></name><name><surname>Campos-Neto</surname><given-names>A</given-names></name></person-group><article-title>Selective inability of spleen antigen presenting cells
from <italic>Leishmania donovani</italic> infected hamsters to mediate specific T
cell proliferation to parasite antigens</article-title><source>Parasite Immunol</source><year>1992</year><volume>14</volume><fpage>49</fpage><lpage>58</lpage><pub-id pub-id-type="pmid">1557230</pub-id></element-citation></ref><ref id="B96"><label>96</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rodríguez Roque</surname><given-names>AL</given-names></name><name><surname>Cupolillo</surname><given-names>E</given-names></name><name><surname>Marchevssky</surname><given-names>RS</given-names></name><name><surname>Jasen</surname><given-names>AM</given-names></name></person-group><article-title><italic>Thrichomys laurentius</italic> (Rodentia; Echimyidae) as a putative
reservoir of <italic>Leishmania infantum</italic> and <italic>L.
braziliensis</italic>: patterns of experimental infection</article-title><source>Plos Negl Trop Dis</source><year>2010</year><volume>4</volume><elocation-id></elocation-id></element-citation></ref><ref id="B97"><label>97</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rogers</surname><given-names>M</given-names></name><name><surname>Kropf</surname><given-names>P</given-names></name><name><surname>Choi</surname><given-names>B</given-names></name><name><surname>Dillon</surname><given-names>R</given-names></name><name><surname>Podinovskaia</surname><given-names>M</given-names></name><name><surname>Bates</surname><given-names>P</given-names></name><etal></etal></person-group><article-title>Proteophosophoglycans regurgitated by
<italic>Leishmania</italic>-infected sand flies target the L-arginine
metabolism of host macrophages to promote parasite survival</article-title><source>PLoS Pathog</source><year>2009</year><volume>5</volume><fpage>555</fpage><lpage>568</lpage></element-citation></ref><ref id="B98"><label>98</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sacks</surname><given-names>D</given-names></name><name><surname>Noben-Trauth</surname><given-names>N</given-names></name></person-group><article-title>The immunology of susceptibility and resistance to
<italic>Leishmania major</italic> in mice</article-title><source>Nat Rev</source><year>2002</year><volume>2</volume><fpage>845</fpage><lpage>858</lpage></element-citation></ref><ref id="B99"><label>99</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Santaella</surname><given-names>J</given-names></name><name><surname>Ocampo</surname><given-names>CB</given-names></name><name><surname>Saravia</surname><given-names>NG</given-names></name><name><surname>Méndez</surname><given-names>F</given-names></name><name><surname>Góngora</surname><given-names>R</given-names></name><name><surname>Gomez</surname><given-names>MA</given-names></name><etal></etal></person-group><article-title><italic>Leishmania</italic> (<italic>Viannia</italic>) infection in the domestic
dog in Chaparral, Colombia</article-title><source>Am J Trop Med Hyg</source><year>2011</year><volume>84</volume><fpage>674</fpage><lpage>680</lpage><pub-id pub-id-type="pmid">21540374</pub-id></element-citation></ref><ref id="B100"><label>100</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Satoskar</surname><given-names>A</given-names></name><name><surname>Bluethmann</surname><given-names>H</given-names></name><name><surname>Alexander</surname><given-names>J</given-names></name></person-group><article-title>Disruption of the murine interleukin-4 gene inhibits
disease progression during <italic>Leishmania mexicana</italic> infection but does
not increase control of <italic>Leishmania donovani</italic>infection</article-title><source>Infect Immun</source><year>1995</year><volume>63</volume><fpage>4894</fpage><lpage>4899</lpage><pub-id pub-id-type="pmid">7591152</pub-id></element-citation></ref><ref id="B101"><label>101</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Senior</surname><given-names>K</given-names></name></person-group><article-title>Vector-borne diseases threaten Europe</article-title><source>Lancet Infect Dis</source><year>2008</year><volume>8</volume><fpage>531</fpage><lpage>532</lpage><pub-id pub-id-type="pmid">18754168</pub-id></element-citation></ref><ref id="B102"><label>102</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Shweash</surname><given-names>M</given-names></name><name><surname>McGachy</surname><given-names>HA</given-names></name><name><surname>Schroeder</surname><given-names>J</given-names></name><name><surname>Neamatallah</surname><given-names>T</given-names></name><name><surname>Bryant</surname><given-names>CE</given-names></name><name><surname>Millington</surname><given-names>O</given-names></name><etal></etal></person-group><article-title><italic>Leishmania mexicana</italic> promastigotes inhibit macrophage IL-12
production via TLR-4 dependent COX-2, iNOS and arginase-1
expression</article-title><source>Mol Immunol</source><year>2011</year><volume>48</volume><fpage>1800</fpage><lpage>1808</lpage><pub-id pub-id-type="pmid">21664694</pub-id></element-citation></ref><ref id="B103"><label>103</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Soong</surname><given-names>L</given-names></name><name><surname>Chang</surname><given-names>CH</given-names></name><name><surname>Sun</surname><given-names>J</given-names></name><name><surname>Longley</surname><given-names>BJ</given-names><suffix>Jr</suffix></name><name><surname>Ruddle</surname><given-names>NH</given-names></name><name><surname>Flavell</surname><given-names>RA</given-names></name><etal></etal></person-group><article-title>Role of CD4+ T cells in pathogenesis associated with
<italic>Leishmania amazonensis</italic> infection</article-title><source>J Immunol</source><year>1997</year><volume>158</volume><fpage>5374</fpage><lpage>5383</lpage><pub-id pub-id-type="pmid">9164958</pub-id></element-citation></ref><ref id="B104"><label>104</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sosa-Bibiano</surname><given-names>EI</given-names></name><name><surname>Van Wynsberghe</surname><given-names>NR</given-names></name><name><surname>Canto-Lara</surname><given-names>SB</given-names></name><name><surname>Andrade-Narvaez</surname><given-names>FJ</given-names></name></person-group><article-title>Preliminary study towards a novel experimental model to
study localized cutaneous leishmaniasis caused by <italic>Leishmania (Leishmania)
mexicana</italic></article-title><source>Rev Inst Med Trop Sao Paulo</source><year>2012</year><volume>54</volume><fpage>165</fpage><lpage>169</lpage><pub-id pub-id-type="pmid">22634889</pub-id></element-citation></ref><ref id="B105"><label>105</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Souza-Lemos</surname><given-names>C</given-names></name><name><surname>De-Campos</surname><given-names>SN</given-names></name><name><surname>Teva</surname><given-names>A</given-names></name><name><surname>Porrozzi</surname><given-names>R</given-names></name><name><surname>Grimaldi</surname><given-names>G</given-names><suffix>Jr</suffix></name></person-group><article-title><italic>In situ</italic> characterization of the granulomatous immune response
with time in nonhealing lesional skin of <italic>Leishmania
braziliensis</italic>-infected rhesus macaques (<italic>Macaca
mulatta</italic>)</article-title><source>Vet Immun Immunopathol</source><year>2011</year><volume>142</volume><fpage>147</fpage><lpage>155</lpage></element-citation></ref><ref id="B106"><label>106</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Stamm</surname><given-names>LM</given-names></name><name><surname>Räisänen-Sokolowski</surname><given-names>A</given-names></name><name><surname>Okano</surname><given-names>M</given-names></name><name><surname>Russell</surname><given-names>ME</given-names></name><name><surname>David</surname><given-names>JR</given-names></name><name><surname>Satoskar</surname><given-names>AR</given-names></name></person-group><article-title>Mice with STAT6-targeted gene disruption develop a Th1
response and control cutaneous leishmaniasis</article-title><source>J Immunol</source><year>1998</year><volume>161</volume><fpage>6180</fpage><lpage>6188</lpage><pub-id pub-id-type="pmid">9834104</pub-id></element-citation></ref><ref id="B107"><label>107</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Szatkiewicz</surname><given-names>JP</given-names></name><name><surname>Beane</surname><given-names>GL</given-names></name><name><surname>Ding</surname><given-names>Y</given-names></name><name><surname>Hutchins</surname><given-names>L</given-names></name><name><surname>Pardo-Manuel de Villena</surname><given-names>F</given-names></name><name><surname>Churchill</surname><given-names>GA</given-names></name></person-group><article-title>An imputed genotype resource for the laboratory
mouse</article-title><source>Mamm Genome</source><year>2008</year><volume>19</volume><fpage>199</fpage><lpage>208</lpage><pub-id pub-id-type="pmid">18301946</pub-id></element-citation></ref><ref id="B108"><label>108</label><element-citation publication-type="journal"><person-group person-group-type="author"><collab>The Working Group on Research Priorities for
Development of Leishmaniasis Vaccines</collab><name><surname>Nery Costa</surname><given-names>CH</given-names></name><name><surname>Peters</surname><given-names>NC</given-names></name><name><surname>Maruyama</surname><given-names>SR</given-names></name><name><surname>Brito</surname><given-names>EC de</given-names><suffix>Jr</suffix></name><name><surname>Santos</surname><given-names>IK</given-names></name></person-group><article-title>Vaccines for the leishmaniases: proposal for a research
agenda.</article-title><source>Plos Negl Trop Dis.</source><year>2011</year><volume>5</volume><elocation-id></elocation-id><pub-id pub-id-type="doi">10.1371/journal.pntd.0000943</pub-id></element-citation></ref><ref id="B109"><label>109</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Van Wynsberghe</surname><given-names>NR</given-names></name><name><surname>Canto-Lara</surname><given-names>SB</given-names></name><name><surname>Damián-Centeno</surname><given-names>AG</given-names></name><name><surname>Itzá-Ortiz</surname><given-names>M</given-names></name><name><surname>Andrade-Narváez</surname><given-names>FJ</given-names></name></person-group><article-title>Retention of <italic>Leishmania (L.) mexicana</italic>in naturally infected rodents from the State of Campeche, Mexico</article-title><source>Mem Inst Oswaldo Cruz</source><year>2000</year><volume>95</volume><fpage>595</fpage><lpage>600</lpage><pub-id pub-id-type="pmid">10998205</pub-id></element-citation></ref><ref id="B110"><label>110</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Van Wynsberghe</surname><given-names>NR</given-names></name><name><surname>Canto-Lara</surname><given-names>SB</given-names></name><name><surname>Sosa-Bibiano</surname><given-names>EI</given-names></name><name><surname>Rivero-Cárdenas</surname><given-names>NA</given-names></name><name><surname>Andrade-Narváez</surname><given-names>FJ</given-names></name></person-group><article-title>Comparison of small mammal prevalence of
<italic>Leishmania (Leishmania) mexicana</italic> in five foci of cutaneous
leishmaniasis in the State of Campeche, México</article-title><source>Rev Inst Med Trop Sao Paulo</source><year>2009</year><volume>51</volume><fpage>87</fpage><lpage>94</lpage><pub-id pub-id-type="pmid">19390737</pub-id></element-citation></ref><ref id="B111"><label>111</label><element-citation publication-type="book"><person-group person-group-type="author"><name><surname>Villanueva Lizama</surname><given-names>LE</given-names></name></person-group><article-title>Implementación de técnicas moleculares para el análisis
de citocinas Th2 (Interleucina 4, interleucina 10 y factor transformador del
crecimiento beta) de <italic>Peromyscus yucatanicus</italic></article-title><publisher-loc>Mérida</publisher-loc><publisher-name>Universidad Autónoma de Yucatán</publisher-name><year>2011</year></element-citation></ref><ref id="B112"><label>112</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Vouldoukis</surname><given-names>I</given-names></name><name><surname>Drapier</surname><given-names>JC</given-names></name><name><surname>Nüssler</surname><given-names>AK</given-names></name><name><surname>Tselentis</surname><given-names>Y</given-names></name><name><surname>Silva</surname><given-names>O Da</given-names></name><name><surname>Gentilini</surname><given-names>M</given-names></name><etal></etal></person-group><article-title>Canine visceral leishmaniasis: successful chemotherapy
induces macrophage antileishmanial activity via the L-arginine nitric oxide
pathway</article-title><source>Antimicrob Agents Chemother</source><year>1996</year><volume>40</volume><fpage>253</fpage><lpage>256</lpage><pub-id pub-id-type="pmid">8787918</pub-id></element-citation></ref><ref id="B113"><label>113</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wilson</surname><given-names>ME</given-names></name><name><surname>Jeronimo</surname><given-names>SMB</given-names></name><name><surname>Pearson</surname><given-names>RD</given-names></name></person-group><article-title>Immunopathogenesis of infection with the visceralizing
<italic>Leishmania</italic> species</article-title><source>Microb Pathog</source><year>2005</year><volume>38</volume><fpage>147</fpage><lpage>160</lpage><pub-id pub-id-type="pmid">15797810</pub-id></element-citation></ref></ref-list></back></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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