Frequent and seasonally variable sublethal anthrax infections are accompanied by short‐lived immunity in an endemic system

Abstract

Summary Few studies have examined host-pathogen interactions in wildlife from an immunological perspective, particularly in the context of seasonal and longitudinal dynamics. In addition, though most ecological immunology studies employ serological antibody assays, endpoint titer determination is usually based on subjective criteria and needs to be made more objective. Despite the fact that anthrax is an ancient and emerging zoonotic infectious disease found worldwide, its natural ecology is not well understood. In particular, little is known about the adaptive immune responses of wild herbivore hosts against Bacillus anthracis. Working in the natural anthrax system of Etosha National Park, Namibia, we collected 154 serum samples from plains zebra (Equus quagga), 21 from springbok (Antidorcas marsupialis), and 45 from African elephants (Loxodonta africana) over 2-3 years, resampling individuals when possible for seasonal and longitudinal comparisons. We used enzyme-linked immunosorbent assays to measure anti-anthrax antibody titers and developed three increasingly conservative models to determine endpoint titers with more rigorous, objective mensuration. Between 52-87% of zebra, 0-15% of springbok, and 3-52% of elephants had measurable anti-anthrax antibody titers, depending on the model used. While the ability of elephants and springbok to mount anti-anthrax adaptive immune responses is still equivocal, our results indicate that zebra in ENP often survive sublethal anthrax infections, encounter most B. anthracis in the wet season, and can partially booster their immunity to B. anthracis. Thus, rather than being solely a lethal disease, anthrax often occurs as a sublethal infection in some susceptible hosts. Though we found that adaptive immunity to anthrax wanes rapidly, subsequent and frequent sublethal B. anthracis infections cause maturation of anti-anthrax immunity. By triggering host immune responses, these common sublethal infections may act as immunomodulators and affect population dynamics through indirect immunological and co-infection effects. In addition, with our three endpoint titer models, we introduce more mensuration rigor into serological antibody assays, even under the often-restrictive conditions that come with adapting laboratory immunology methods to wild systems. With these methods we identified significantly more zebras responding immunologically to anthrax than have previous studies using less comprehensive titer analyses.

Gastrointestinal helminths may affect host susceptibility to anthrax through seasonal immune trade-offs

“…In support of this, we found that anti-PA titer prevalence was significantly, positively related to rainfall in the PA GEE ( Figure 3B), likely reflecting this increased exposure to B. anthracis during the wet season, with a subsequent immune response if hosts are exposed to sublethal doses [32]. As we previously found evidence that mean time for negative seroconversion in titer-positive animals is less than six months [32], we are confident that the rainfallcorrelated immune signatures represent recent, seasonal B. anthracis exposure. This immune signature, coupled with the simultaneously significantly increased rates anthrax deaths supports the assertion that differential exposure to anthrax at least partly drives its seasonality in this system.…”

“…There is as yet no definitive evidence that anthrax can multiply in the soil in natural systems [25]; though see [29,30], and thus anthrax spore levels likely do not increase under seasonal conditions. Given the endemic nature of anthrax in ENP, the prolonged survival times of spores in the environment [28,31], the fact that anthrax deaths and sublethal infections do occur throughout the year in this system [32], it is likely that animals come into contact with anthrax spores in all seasons, though some hosts may also ingest more B. anthracis in soil during wetter times [27]. While multiple factors are likely involved in the timing of anthrax outbreaks, we hypothesize that seasonal changes in host coinfection and immune factors may influence host susceptibility to this environmental pathogen.…”

“…While multiple factors are likely involved in the timing of anthrax outbreaks, we hypothesize that seasonal changes in host coinfection and immune factors may influence host susceptibility to this environmental pathogen. Anthrax can cause death within hours to days [33], though there is evidence that even very susceptible host species can experience a sublethal dose of anthrax and survive, in part, due to a humoral immune response against the anthrax protective antigen (PA) toxin [32,34]. These anti-PA antibodies have been shown to be essential for adaptive protection against anthrax and can mature through memory responses with multiple infections, though otherwise tend to last less than six months [32,35,36].…”

“…Anthrax can cause death within hours to days [33], though there is evidence that even very susceptible host species can experience a sublethal dose of anthrax and survive, in part, due to a humoral immune response against the anthrax protective antigen (PA) toxin [32,34]. These anti-PA antibodies have been shown to be essential for adaptive protection against anthrax and can mature through memory responses with multiple infections, though otherwise tend to last less than six months [32,35,36]. As a bacterial infection, anthrax provokes a primarily Th1-type immune response, a response in opposition to the Th2-type immune response driven by helminth infections [37].…”

Fatal attraction: vegetation responses to nutrient inputs attract herbivores to infectious anthrax carcass sites

“…BA is the causative agent of anthrax, a virulent disease that can kill herbivorous hosts within two weeks of a lethal exposure [20] (although sublethal exposures do occur [21]). BA is an environmentally transmitted pathogen that forms hardy spores, which can persist for years in the environment [22].…”