BACKGROUND: Salivary proteins of Triatoma infestans elicit humoral immune responses in their vertebrate hosts. These immune responses indicate exposure to triatomines and thus can be a useful epidemiological tool to estimate triatomine infestation. In the present study, we analyzed antibody responses of guinea pigs to salivary antigens of different developmental stages of four T. infestans strains originating from domestic and/or peridomestic habitats in Argentina, Bolivia, Chile and Peru. We aimed to identify developmental stage- and strain-specific salivary antigens as potential markers of T. infestans exposure. METHODOLOGY AND PRINCIPAL FINDINGS: In SDS-PAGE analysis of salivary proteins of T. infestans the banding pattern differed between developmental stages and strains of triatomines. Phenograms constructed from the salivary profiles separated nymphal instars, especially the 5th instar, from adults. To analyze the influence of stage- and strain-specific differences in T. infestans saliva on the antibody response of guinea pigs, twenty-one guinea pigs were exposed to 5th instar nymphs and/or adults of different T. infestans strains. Western blot analyses using sera of exposed guinea pigs revealed stage- and strain-specific variations in the humoral response of animals. In total, 27 and 17 different salivary proteins reacted with guinea pig sera using IgG and IgM antibodies, respectively. Despite all variations of recognized salivary antigens, an antigen of 35 kDa reacted with sera of almost all challenged guinea pigs. CONCLUSION: Salivary antigens are increasingly considered as an epidemiological tool to measure exposure to hematophagous arthropods, but developmental stage- and strain-specific variations in the saliva composition and the respective differences of immunogenicity are often neglected. Thus, the development of a triatomine exposure marker for surveillance studies after triatomine control campaigns requires detailed investigations. Our study resulted in the identification of a potential antigen as useful marker of T. infestans exposure.

Institute of Parasitology Biology Centre of the Academy of Sciences of Czech Republic Ceske Budejovice Czech Republic

Institute of Parasitology Biology Centre of the Academy of Sciences of Czech Republic Ceske Budejovice Czech Republic; Faculty of Science University of South Bohemia Ceske Budejovice Czech Republic

Universidad Peruana Cayetano Heredia Sede de Arequipa Arequipa Peru

Universidad Peruana Cayetano Heredia Sede de Arequipa Arequipa Peru; Department of Biostatistics and Epidemiology Center for Clinical Epidemiology and Biostatistics School of Medicine University of Pennsylvania Philadelphia Pennsylvania United States of America

Zoology Parasitology Group Ruhr University Bochum Bochum Germany

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Berry AA, Nyunt MM, Plowe CV (2011) Malaria: clinical and epidemiological aspects. In: Kaufmann SHE, Rouse BT, Sacks DL, editors. Immune response to infection. Washington, DC: ASM Press. pp. 633–641.

Desjeux P (2004) Leishmaniasis: current situation and new perspectives. Comp Immunol Microbiol Infect Dis 27: 305–318. PubMed

Stanek G, Wormser GP, Gray J, Strle F (2012) Lyme borreliosis. Lancet 379: 461–473. PubMed

Rassi A Jr, Rassi A, Marin-Neto JA (2010) Chagas disease. Lancet 375: 1388–1402. PubMed

Gubler DJ (1998) Resurgent vector-borne diseases as a global health problem. Emerg Infect Dis 4: 442–450. PubMed PMC

Kalluri S, Gilruth P, Rogers D, Szczur M (2007) Surveillance of arthropod vector-borne infectious diseases using remote sensing techniques: a review. Plos Pathog 3: 1361–1371. PubMed PMC

Beugnet F, Marie JL (2009) Emerging arthropod-borne diseases of companion animals in Europe. Vet Parasitol 163: 298–305. PubMed

Otranto D, Wall R (2008) New strategies for the control of arthropod vectors of disease in dogs and cats. Med Vet Entomol 22: 291–302. PubMed

Ribeiro JMC (1995) Blood-feeding arthropods - live syringes or invertebrate pharmacologists. Infect Agent Dis 4: 143–152. PubMed

Andrade BB, Texeira CR, Barral A, Barral-Netto M (2005) Haematophagous arthropod saliva and host defense system: a tale of tear and blood. An Acad Bras Cienc 77: 665–693. PubMed

Francischetti IMB, Sá-Nunes A, Mans BJ, Santos IM, Ribeiro JMC (2009) The role of saliva in tick feeding. Front Biosci 14: 2051–2088. PubMed PMC

Fontaine A, Diouf I, Bakkali N, Missé D, Pagès F, et al. (2011) Implication of haematophagous arthropod salivary proteins in host-vector interactions. Parasit Vectors 4: 187. PubMed PMC

Schwartz BS, Ribeiro JM, Goldstein MD (1990) Anti-tick antibodies: an epidemiologic tool in Lyme disease research. Am J Epidemiol 132: 58–66. PubMed

Rohoušová I, Ozensoy S, Ozbel Y, Volf P (2005) Detection of species-specific antibody response of humans and mice bitten by sand flies. Parasitology 130: 493–499. PubMed

Marzouki S (2011) Characterization of the antibody response to the saliva of Phlebotomus papatasi in people living in endemic areas of cutaneous leishmaniasis. Am J Trop Med Hyg 85: 653–661. PubMed PMC

Vlková M, Rohoušová I, Hostomská J, Pohanková L, Zidková L, et al. (2012) Kinetics of antibody response in BALB/c and C57BL/6 mice bitten by Phlebotomus papatasi . PLoS Negl Trop Dis 6: e1719. PubMed PMC

Orlandi-Pradines E, Almeras L, de Senneville LD, Barbe S, Remoué F, et al. (2007) Antibody response against saliva antigens of Anopheles gambiae and Aedes aegypti in travellers in tropical Africa. Microbes Infect 9: 1454–1462. PubMed

Doucoure S, Mouchet F, Cornelie S, DeHecq JS, Rutee AH, et al. (2012) Evaluation of the human IgG antibody response to Aedes albopictus saliva as a new specific biomarker of exposure to vector bites. PLoS Negl Trop Dis 6: e1487. PubMed PMC

Ogden NH, Casey ANJ, Lawrie CH, French NP, Woldehiwet Z, et al. (2002) IgG responses to salivary gland extract of Ixodes ricinus ticks vary inversely with resistance in naturally exposed sheep. Med Vet Entomol 16: 186–192. PubMed

Kashino SS, Resende J, Sacco AM, Rocha C, Proenca L, et al. (2005) Boophilus microplus: the pattern of bovine immunoglobulin isotype responses to high and low tick infestations. Exp Parasitol 110: 12–21. PubMed

Sanders ML, Glass GE, Scott AL, Schwartz BS (1998) Kinetics and cross-species comparisons of host antibody responses to lone star ticks and American dog ticks (Acari: Ixodidae). J Med Entomol 35: 849–856. PubMed

Cross ML, Cupp MS, Cupp EW, Galloway AL, Enriquez FJ (1993) Modulation of murine immunological responses by salivary-gland extract of Simulium vittatum (Diptera, Simuliidae). J Med Entomol 30: 928–935. PubMed

Cross ML, Cupp MS, Cupp EW, Ramberg FB, Enriquez FJ (1993) Antibody-responses of Balb/C mice to salivary antigens of hematophagous black flies (Diptera, Simuliidae). J Med Entomol 30: 725–734. PubMed

Drame PM, Poinsignon A, Besnard P, Le Mire J, Dos-Santos MA, et al. (2010) Human antibody response to Anopheles gambiae saliva: an immuno-epidemiological biomarker to evaluate the efficacy of insecticide-treated nets in malaria vector control. Am J Trop Med Hyg 83: 115–121. PubMed PMC

Schwarz A, Juarez JA, Richards J, Rath B, Machaca VQ, et al. (2011) Anti-triatomine saliva immunoassays for the evaluation of impregnated netting trials against Chagas disease transmission. Int J Parasitol 41: 591–594. PubMed PMC

Gidwani K, Picado A, Rijal S, Singh SP, Roy L, et al. (2011) Serological markers of sand fly exposure to evaluate insecticidal nets against visceral leishmaniasis in India and Nepal: a cluster-randomized trial. PLoS Negl Trop Dis 5: e1296. PubMed PMC

Barral A, Honda E, Caldas A, Costa J, Vinhas V, et al. (2000) Human immune response to sand fly salivary gland antigens: a useful epidemiological marker? Am J Trop Med Hyg 62: 740–745. PubMed

Lombardo F, Ronca R, Rizzo C, Mestres-Simon M, Lanfrancotti A, et al. (2009) The Anopheles gambiae salivary protein gSG6: an anopheline-specific protein with a blood-feeding role. Insect Biochem Mol Biol 39: 457–466. PubMed PMC

Poinsignon A, Cornelie S, Mestres-Simon M, Lanfrancotti A, Rossignol M, et al. (2008) Novel peptide marker corresponding to salivary protein gSG6 potentially identifies exposure to Anopheles bites. Plos One 3: e2472. PubMed PMC

Poinsignon A, Cornelie S, Ba F, Boulanger D, Sow C, et al. (2009) Human IgG response to a salivary peptide, gSG6-PI, as a new immuno-epidemiological tool for evaluating low-level exposure to Anopheles bites. Malaria J 8: 198. PubMed PMC

Rizzo C, Ronca R, Fiorentino G, Verra F, Mangano V, et al. (2011) Humoral response to the Anopheles gambiae salivary protein gSG6: a serological indicator of exposure to Afrotropical malaria vectors. Plos One 6: e17980. PubMed PMC

Poinsignon A, Samb B, Doucoure S, Drame PM, Sarr JB, et al. (2010) First attempt to validate the gSG6-P1 salivary peptide as an immuno-epidemiological tool for evaluating human exposure to Anopheles funestus bites. Trop Med Int Health 15: 1198–1203. PubMed

Sanders ML, Jaworski DC, Sanchez JL, DeFraites RE, Glass GE, et al. (1998) Antibody to a cDNA-derived calreticulin protein from Amblyomma americanum as a biomarker of tick exposure in humans. Am J Trop Med Hyg 59: 279–285. PubMed

Alarcon-Chaidez F, Ryan R, Wikel S, Dardick K, Lawler C, et al. (2006) Confirmation of tick bite by detection of antibody to Ixodes calreticulin salivary protein. Clin Vaccine Immunol 13: 1217–1222. PubMed PMC

Souza AP, Andrade BB, Aquino D, Entringer P, Miranda JC, et al. (2010) Using recombinant proteins from Lutzomyia longipalpis saliva to estimate human vector exposure in visceral leishmaniasis endemic areas. PLoS Negl Trop Dis 4: e649. PubMed PMC

Teixeira C, Gomes R, Collin N, Reynoso D, Jochim R, et al. (2010) Discovery of markers of exposure specific to bites of Lutzomyia longipalpis, the vector of Leishmania infantum chagasi in Latin America. PLoS Negl Trop Dis 4: e638. PubMed PMC

Schwarz A, Sternberg JM, Johnston V, Medrano-Mercado N, Anderson JM, et al. (2009) Antibody responses of domestic animals to salivary antigens of Triatoma infestans as biomarkers for low-level infestation of triatomines. Int J Parasitol 39: 1021–1029. PubMed PMC

Schwarz A, Medrano-Mercado N, Billingsley PF, Schaub GA, Sternberg JM (2010) IgM-antibody responses of chickens to salivary antigens of Triatoma infestans as early biomarkers for low-level infestation of triatomines. Int J Parasitol 40: 1295–1302. PubMed

Schwarz A, Helling S, Collin N, Teixeira CR, Medrano-Mercado N, et al. (2009) Immunogenic salivary proteins of Triatoma infestans: development of a recombinant antigen for the detection of low-level infestation of triatomines. PLoS Negl Trop Dis 3: e532. PubMed PMC

Castro-Sesquen YE, Gilman RH, Yauri V, Angulo N, Verastegui M, et al. (2011) Cavia porcellus as a model for experimental infection by Trypanosoma cruzi . Am J Pathol 179: 281–288. PubMed PMC

Gürtler RE, Cecere MC, Lauricella MA, Cardinal MV, Kitron U, et al. (2007) Domestic dogs and cats as sources of Trypanosoma cruzi infection in rural northwestern Argentina. Parasitology 134: 69–82. PubMed PMC

Gürtler RE, Cecere MC, Lauricella IA, Petersen RM, Chuit R, et al. (2005) Incidence of Trypanosoma cruzi infection among children following domestic reinfestation after insecticide spraying in rural Northwestern Argentina. Am J Trop Med Hyg 73: 95–103. PubMed PMC

Levy MZ, Bowman NM, Kawai V, Waller LA, Cornejo del Carpio JG, et al. (2006) Periurban Trypanosoma cruzi-infected Triatoma infestans, Arequipa, Peru. Emerg Infect Dis 12: 1345–1352. PubMed PMC

Rohoušová I, Volfová V, Nová S, Volf P (2012) Individual variability of salivary gland proteins in three Phlebotomus species. Acta Trop 122: 80–86. PubMed

Barbosa SE, Diotaiuti L, Braga EM, Pereira MH (2004) Variability of the salivary proteins of 20 Brazilian populations of Panstrongylus megistus (Hemiptera: Reduviidae: Triatominae). Acta Trop 92: 25–33. PubMed

Barbosa SE, Diotaiuti L, Soares RP, Pereira MH (1999) Differences in saliva composition among three Brazilian populations of Panstrongylus megistus (Hemiptera, Reduviidae). Acta Trop 72: 91–98. PubMed

Volf P, Tesarová P, Nohýnkova E (2000) Salivary proteins and glycoproteins in phlebotomine sandflies of various species, sex and age. Med Vet Entomol 14: 251–256. PubMed

Guarneri AA, Diotaiuti L, Gontijo NF, Gontijo AF, Pereira MH (2003) Blood-feeding performance of nymphs and adults of Triatoma brasiliensis on human hosts. Acta Trop 87: 361–370. PubMed

Meiser CK, Piechura H, Meyer HE, Warscheid B, Schaub GA, et al. (2010) A salivary serine protease of the haematophagous reduviid Panstrongylus megistus: sequence characterization, expression pattern and characterization of proteolytic activity. Insect molecular biology 19: 409–421. PubMed

Pavlicek A, Hrda S, Flegr J (1999) Free-Tree–freeware program for construction of phylogenetic trees on the basis of distance data and bootstrap/jackknife analysis of the tree robustness. Application in the RAPD analysis of genus Frenkelia. Folia biologica 45: 97–99. PubMed

Page RD (1996) TreeView: an application to display phylogenetic trees on personal computers. Computer applications in the biosciences : CABIOS 12: 357–358. PubMed

Team RC (2013) R: A language and environment for statistical computing. R Foundation for Statistical Computing. Vienna, Austria: URL http://www.R-project.org/.

Hashimoto K, Yoshioka K (2012) Review: surveillance of Chagas disease. Adv Parasitol 79: 375–428. PubMed

Yamagata Y, Nakagawa J (2006) Control of Chagas disease. Adv Parasitol 61: 129–165. PubMed

Abad-Franch F, Santos WS, Schofield CJ (2010) Research needs for Chagas disease prevention. Acta Trop 115: 44–54. PubMed

Dias JCP, Silveira AC, Schofield CJ (2002) The impact of Chagas disease control in Latin America - a review. Mem Inst Oswaldo Cruz 97: 603–612. PubMed

Schofield CJ, Jannin J, Salvatella R (2006) The future of Chagas disease control. Trends Parasitol 22: 583–588. PubMed

Dias JCP (2007) Southern Cone Initiative for the elimination of domestic populations of Triatoma infestans and the interruption of transfusional Chagas disease. Historical aspects, present situation, and perspectives. Mem Inst Oswaldo Cruz 102: 11–18. PubMed

Lardeux F, Depickere S, Duchon S, Chavez T (2010) Insecticide resistance of Triatoma infestans (Hemiptera, Reduviidae) vector of Chagas disease in Bolivia. Trop Med Int Health 15: 1037–1048. PubMed

Picollo MI, Vassena C, Santo Orihuela P, Barrios S, Zaidemberg M, et al. (2005) High resistance to pyrethroid insecticides associated with ineffective field treatments in Triatoma infestans (Hemiptera: Reduviidae) from Northern Argentina. J Med Entomol 42: 637–642. PubMed

Gürtler RE, Canale DM, Spillmann C, Stariolo R, Salomon OD, et al. (2004) Effectiveness of residual spraying of peridomestic ecotopes with deltamethrin and permethrin on Triatoma infestans in rural western Argentina: a district-wide randomized trial. Bull World Health Organ 82: 196–205. PubMed PMC

Cecere MC, Gurtler RE, Canale D, Chuit R, Cohen JE (1997) The role of the peridomiciliary area in the elimination of Triatoma infestans from rural Argentine communities. Rev Panam Salud Publica 1: 273–279. PubMed

Guhl F, Pinto N, Aguilera G (2009) Sylvatic triatominae: a new challenge in vector control transmission. Mem Inst Oswaldo Cruz 104: 71–75. PubMed

Gürtler RE (2009) Sustainability of vector control strategies in the Gran Chaco Region: current challenges and possible approaches. Mem Inst Oswaldo Cruz 104: 52–59. PubMed PMC

Gürtler RE, Chuit R, Cecere MC, Castanera MB (1995) Detecting domestic vectors of Chagas disease: a comparative trial of six methods in north-west Argentina. Bull World Health Organ 73: 487–494. PubMed PMC

De Marco RJ, Gurtler RE, Salomon OD, Chuit R (1999) Small-scale field trial of a sensing device for detecting peridomestic populations of Triatoma infestans (Hemiptera: Reduviidae) in northwestern Argentina. J Med Entomol 36: 884–887. PubMed

Vazquez-Prokopec GM, Ceballos LA, Salomon OD, Gurtler RE (2002) Field trials of an improved cost-effective device for detecting peridomestic populations of Triatoma infestans (Hemiptera: Reduviidae) in rural Argentina. Mem Inst Oswaldo Cruz 97: 971–977. PubMed

Volf P, Grubhoffer L, Hosek P (1993) Characterization of salivary-gland antigens of Triatoma infestans and antigen-specific serum antibody-response in mice exposed to bites of T. infestans . Vet Parasitol 47: 327–337. PubMed

Nascimento RJ, Santana JM, Lozzi SP, Araujo CN, Teixeira AR (2001) Human IgG1 and IgG4: the main antibodies against Triatoma infestans (Hemiptera: Reduviidae) salivary gland proteins. Am J Trop Med Hyg 65: 219–226. PubMed

Bayer AM, Hunter GC, Gilman RH, del Carpio JGC, Naquira C, et al. (2009) Chagas disease, migration and community settlement patterns in Arequipa, Peru. PLoS Negl Trop Dis 3: e567. PubMed PMC

Delgado S, Castillo Neyra R, Quispe Machaca VR, Ancca Juarez J, Chou Chu L, et al. (2011) A history of Chagas disease transmission, control, and re-emergence in peri-rural La Joya, Peru. PLoS Negl Trop Dis 5: e970. PubMed PMC

Gürtler RE, Chuit R, Cecere MC, Castanera MB, Cohen JE, et al. (1998) Household prevalence of seropositivity for Trypanosoma cruzi in three rural villages in northwest Argentina: environmental, demographic, and entomologic associations. Am J Trop Med Hyg 59: 741–749. PubMed

Gurevitz JM, Ceballos LA, Gaspe MS, Alvarado-Otegui JA, Enriquez GF, et al. (2011) Factors affecting infestation by Triatoma infestans in a rural area of the humid Chaco in Argentina: a multi-model inference approach. PLoS Negl Trop Dis 5: e1349. PubMed PMC

Levy MZ, Quispe-Machaca VR, Ylla-Velasquez JL, Waller LA, Richards JM, et al. (2008) Impregnated netting slows infestation by Triatoma infestans . Am J Trop Med Hyg 79: 528–534. PubMed PMC

Gürtler RE, Kitron U, Cecere MC, Segura EL, Cohen JE (2007) Sustainable vector control and management of Chagas disease in the Gran Chaco, Argentina. Proc Natl Acad Sci U S A 104: 16194–16199. PubMed PMC

Levy MZ, Small DS, Vilhena DA, Bowman NM, Kawai V, et al. (2011) Retracing micro-epidemics of Chagas disease using epicenter regression. PLoS computational biology 7: e1002146. PubMed PMC

Delgado S, Ernst KC, Pumahuanca ML, Yool SR, Comrie AC, et al. (2013) A country bug in the city: urban infestation by the Chagas disease vector Triatoma infestans in Arequipa, Peru. International journal of health geographics 12: 48. PubMed PMC

Human immune response against salivary antigens of Simulium damnosum s.l.: A new epidemiological marker for exposure to blackfly bites in onchocerciasis endemic areas

An updated insight into the Sialotranscriptome of Triatoma infestans: developmental stage and geographic variations