Background Plague is endemic within the central highlands of Madagascar, where its main reservoir is the black rat, Rattus rattus. Typically this species is considered susceptible to plague, rapidly dying after infection inducing the spread of infected fleas and, therefore, dissemination of the disease to humans. However, persistence of transmission foci in the same area from year to year, supposes mechanisms of maintenance among which rat immune responses could play a major role. Immunity against plague and subsequent rat survival could play an important role in the stabilization of the foci. In this study, we aimed to investigate serological responses to plague in wild black rats from endemic areas of Madagascar. In addition, we evaluate the use of a recently developed rapid serological diagnostic test to investigate the immune response of potential reservoir hosts in plague foci. Methodology/Principal Findings We experimentally infected wild rats with Yersinia pestis to investigate short and long-term antibody responses. Anti-F1 IgM and IgG were detected to evaluate this antibody response. High levels of anti-F1 IgM and IgG were found in rats one and three weeks respectively after challenge, with responses greatly differing between villages. Plateau in anti-F1 IgM and IgG responses were reached for as few as 500 and 1500 colony forming units (cfu) inoculated respectively. More than 10% of rats were able to maintain anti-F1 responses for more than one year. This anti-F1 response was conveniently followed using dipsticks. Conclusion/Significance Inoculation of very few bacteria is sufficient to induce high immune response in wild rats, allowing their survival after infection. A great heterogeneity of rat immune responses was found within and between villages which could heavily impact on plague epidemiology. In addition, results indicate that, in the field, anti-F1 dipsticks are efficient to investigate plague outbreaks several months after transmission.
References
[1]
Perry RD, Fetherston JD (1997) Yersinia pestis–etiologic agent of plague. Clin Microbiol Rev 10: 35–66.
[2]
World Health Organization (2010) Human plague: review of regional morbidity and mortality, 2004–2009. Wkly Epidemiol Rec 6: 40–45.
[3]
Chanteau S, Ratsifasoamanana L, Rasoamanana B, Rahalison L, Randriambelosoa J, et al. (1998) Plague, a reemerging disease in Madagascar. Emerg Infect Dis 4: 101–104.
[4]
Duplantier JM, Duchemin JB, Chanteau S, Carniel E (2005) From the recent lessons of the Malagasy foci towards a global understanding of the factors involved in plague reemergence. Vet Res 36: 437–453.
[5]
Rahelinirina S, Duplantier JM, Ratovonjato J, Ramilijaona O, Ratsimba M, et al. (2009) Study on the movement of Rattus rattus and evaluation of the plague dispersion in Madagascar. Vector Borne Zoonotic Dis 10: 77–84.
[6]
Keeling MJ, Gilligan CA (2000) Metapopulation dynamics of bubonic plague. Nature 407: 903–906.
[7]
Gage KL, Kosoy MY (2005) Natural history of plague: perspectives from more than a century of research. Annu Rev Entomol 50: 505–528.
[8]
Tollenaere C, Rahalison L, Ranjalahy M, Duplantier JM, Rahelinirina S, et al. (2010) Susceptibility to Yersinia pestis experimental infection in wild Rattus rattus, reservoir of plague in Madagascar. Ecohealth 7: 242–247.
[9]
Tollenaere C, Duplantier JM, Rahalison L, Ranjalahy M, Brouat C (2010) AFLP genome scan in the black rat (Rattus rattus) from Madagascar: detecting genetic markers undergoing plague-mediated selection. Mol Ecol 20: 1026–1038.
[10]
Tollenaere C, Rahalison L, Ranjalahy M, Rahelinirina S, Duplantier JM, et al. (2008) CCR5 polymorphism and plague resistance in natural populations of the black rat in Madagascar. Infect Genet Evol 8: 891–897.
[11]
Williamson ED, Stagg AJ, Eley SM, Taylor R, Green M, et al. (2007) Kinetics of the immune response to the (F1+V) vaccine in models of bubonic and pneumonic plague. Vaccine 25: 1142–1148.
[12]
Williamson ED, Vesey PM, Gillhespy KJ, Eley SM, Green M, et al. (1999) An IgG1 titre to the F1 and V antigens correlates with protection against plague in the mouse model. Clin Exp Immunol 116: 107–114.
[13]
Butler T, Fu YS, Furman L, Almeida C, Almeida A (1982) Experimental Yersinia pestis infection in rodents after intragastric inoculation and ingestion of bacteria. Infect Immun 36: 1160–1167.
[14]
Chen TH, Meyer KF (1974) Susceptibility and antibody response of Rattus species to experimental plague. J Infect Dis 129:
[15]
Rahalison L, Ranjalahy M, Duplantier JM, Duchemin JB, Ravelosaona J, et al. (2003) Susceptibility to plague of the rodents in Antananarivo, Madagascar. Adv Exp Med Biol 529: 439–442.
[16]
Benner GE, Andrews GP, Byrne WR, Strachan SD, Sample AK, et al. (1999) Immune response to Yersinia outer proteins and other Yersinia pestis antigens after experimental plague infection in mice. Infect Immun 67: 1922–1928.
[17]
Vadyvaloo V, Jarrett C, Sturdevant DE, Sebbane F, Hinnebusch BJ (2010) Transit through the flea vector induces a pretransmission innate immunity resistance phenotype in Yersinia pestis. PLoS Pathog 6: e1000783.
[18]
Sebbane F, Jarrett C, Gardner D, Long D, Hinnebusch BJ (2009) The Yersinia pestis caf1M1A1 fimbrial capsule operon promotes transmission by flea bite in a mouse model of bubonic plague. Infect Immun 77: 1222–1229.
[19]
Quenee LE, Schneewind O (2009) Plague vaccines and the molecular basis of immunity against Yersinia pestis. Hum Vaccin 5: 817–823.
[20]
Anderson GW Jr, Worsham PL, Bolt CR, Andrews GP, Welkos SL, et al. (1997) Protection of mice from fatal bubonic and pneumonic plague by passive immunization with monoclonal antibodies against the F1 protein of Yersinia pestis. Am J Trop Med Hyg 56: 471–473.
[21]
Huang J, D’Souza AJ, Alarcon JB, Mikszta JA, Ford BM, et al. (2009) Protective immunity in mice achieved with dry powder formulation and alternative delivery of plague F1-V vaccine. Clin Vaccine Immunol 16: 719–725.
[22]
Bhattacharya D, Mecsas J, Hu LT (2010) Development of a vaccinia virus based reservoir-targeted vaccine against Yersinia pestis. Vaccine 28: 7683–7689.
[23]
Chanteau S, Rahalison L, Ralafiarisoa L, Foulon J, Ratsitorahina M, et al. (2003) Development and testing of a rapid diagnostic test for bubonic and pneumonic plague. Lancet 361: 211–216.
[24]
Neubauer H, Rahalison L, Brooks TJ, Aleksic S, Chanteau S, et al. (2000) Serodiagnosis of human plague by an anti-F1 capsular antigen specific IgG/IgM ELISA and immunoblot. Epidemiol Infect 125: 593–597.
[25]
Thullier P, Guglielmo V, Rajerison M, Chanteau S (2003) Short report: Serodiagnosis of plague in humans and rats using a rapid test. Am J Trop Med Hyg 69: 450–451.
[26]
Rajerison M, Dartevelle S, Ralafiarisoa LA, Bitam I, Dinh TN, et al. (2009) Development and evaluation of two simple, rapid immunochromatographic tests for the detection of Yersinia pestis antibodies in humans and reservoirs. PLoS Negl Trop Dis 3: e421.
[27]
Leroy F, Chanteau S (1995) Absence d’Yersinia pathogènes autres que Yersinia pestis à Madagascar. Arch Inst Pasteur Madagascar 62: 165.
[28]
Dromigny JA, Ralafiarisoa L, Raharimanana C, Randriananja N, Chanteau S (1998) La sérologie anti-F1 chez la souris OF1, test complémentaire pour le diagnostic de la peste humaine. Arch Inst Pasteur Madagascar 64: 18–20.
[29]
Lorange EA, Race BL, Sebbane F, Joseph Hinnebusch B (2005) Poor vector competence of fleas and the evolution of hypervirulence in Yersinia pestis. J Infect Dis 191: 1907–1912.
[30]
Shepherd AJ, Hummitzsch DE, Leman PA, Swanepoel R, Searle LA (1986) Comparative tests for detection of plague antigen and antibody in experimentally infected wild rodents. J Clin Microbiol 24: 1075–1078.
[31]
Li B, Yang R (2008) Interaction between Yersinia pestis and the host immune system. Infect Immun 76: 1804–1811.
[32]
Wake A, Morita H, Wake M (1978) Mechanisms of long and short term immunity to plague. Immunology 34: 1045–1052.
[33]
Philipovskiy AV, Smiley ST (2007) Vaccination with live Yersinia pestis primes CD4 and CD8 T cells that synergistically protect against lethal pulmonary Y. pestis infection. Infect Immun 75: 878–885.
[34]
Jones A, Bosio C, Duffy A, Goodyear A, Schriefer M, et al. (2010) Protection against pneumonic plague following oral immunization with a non-replicating vaccine. Vaccine 28: 5924–5929.
[35]
Friedlander AM, Welkos SL, Worsham PL, Andrews GP, Heath DG, et al. (1995) Relationship between virulence and immunity as revealed in recent studies of the F1 capsule of Yersinia pestis. Clin Infect Dis 21: S178–181.
[36]
Quenee LE, Cornelius CA, Ciletti NA, Elli D, Schneewind O (2008) Yersinia pestis caf1 variants and the limits of plague vaccine protection. Infect Immun 76: 2025–2036.
