Immune Responses to Plague Infection in Wild Rattus rattus, in Madagascar: A Role in Foci Persistence?

Abstract

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.

Climatic and evolutionary drivers of phase shifts in the plague epidemics of colonial India

“…In a subsequent series of experiments examining infection on the basis of Y. pestis isolation from rats' blood, resistance was shown to prevent the onset of infection rather than merely reduce the severity of symptoms among infected rats (46). The existence of such innate resistance has been confirmed more recently by experimental assays in R. rattus from plague-endemic areas that do not experience infection, disease, or seroconversion after Y. pestis exposure (27,64,71).…”

“…Such conditions are met in the urban plague ecology of colonial India and supported the persistence of polymorphisms in our model in agreement with the findings of historical investigations (42). More recently, field studies have shown similar local persistence of resistance polymorphisms among R. rattus inhabiting plague foci in Madagascar, Asia, and Hawaii (27,31,64,71,94).…”

“…Existing animal-based plague surveillance programs monitor die offs and seroprevalence in rodent populations for early warning signs of the disease's incursion (91,92). However, expansions of resistance among hosts during epizootics could offset population declines and diminish the utility of serology as a marker for local plague transmission (27,64,71,93). The diverse mammal species that may serve as plague hosts further complicate surveillance and control strategies.…”

“…We modeled resistance based on observations that rats evading disease in India also lacked culturable Y. pestis in their bloodstream, which would be necessary to infect fleas (46,60). Such resistance in R. rattus has been called on to explain the ability of individual rats to remain asymptomatic and seronegative after Y. pestis exposure (64), in particular in Madagascar, where R. rattus serves as the primary host of Y. pestis (27,71). Phylogenetic evidence for the recent colonization of Madagascar by R. rattus from India suggests that determinants of Y. pestis resistance among Madagascar rats may have been shared by rats involved in the third plague pandemic in India (97).…”

Current perspectives on the spread of plague in Africa

“…128 However, the immune response to infection may differ even for the same species of rat from the same endemic focus. 130 Genetic structure analysis of R. rattus populations in a rural plague focus showed that ecology may support selection for resistance to plague. 131 Sylvatic plague is much less frequent in the country.…”