Leptospirosis in California sea lions does not fit neatly into the classical dichotomous framework wherein a given host species is either a maintenance host or an accidental host for a particular serovar of pathogenic Leptospira. In sea lions the disease exhibits characteristics of accidental hosts, with pathogenic and sometimes fatal outcomes for individual animals and dramatic outbreaks at the population scale. Yet the disease also appears to circulate at low levels between outbreaks, and asymptomatic seropositivity (even with high titers) is common among adults. Other investigators have reported chronic shedding of leptospires, another characteristic of classical maintenance hosts, with one sea lion reported to shed for at least 154 days following infection .
All available evidence, including several isolates from wild sea lions [15, 18, 28] and comparison of MAT titer scores (Table 3), points to L. interrogans serovar Pomona as the cause of leptospirosis in this population. Mixing of host-adapted and non-adapted traits may be a property of serovar Pomona, which causes disease in pigs, cattle and horses, but can also be shed for 4–6 months by those species [38–40]. Of course, the possibility that other serovars are circulating cannot be excluded without intensive efforts to isolate and identify further leptospires from wild sea lions. Two serovars that were not included in our MAT panel warrant special mention.L. interrogans serovar Autumnalis is increasingly reported in serological studies of dogs in the United States  and is known to cross-react with Pomona in the MAT [11, 41]. L. kirschneri serovar Cynopteri has been detected serologically in a geographically separated population of Z. californianus in the Gulf of California , but the highest titer observed (1:50) was below our threshold for seropositivity. On-going circulation of serovar Pomona remains the most parsimonious explanation for the available data.
If the classical maintenance/accidental-host model of leptospirosis epidemiology is overly simplified, then public health officials must broaden their view of potential reservoirs for this zoonotic pathogen. If the California sea lion population is indeed a reservoir for serovar Pomona, then health warnings regarding leptospirosis risk from stranded sea lions should be extended to non-outbreak periods. The possibility that on-going exposure of sea lions to serovar Pomona arises from continuous contact with an unidentified external reservoir cannot be excluded, but this explanation would only broaden the public health implication to include other host species.
The present study identifies clear cycles of 4–5 year periodicity in seroprevalence to L. interrogans serovar Pomona in the California sea lion population off the California coast. The cyclic pattern arises from changes in the prevalence of high titer scores reflective of recent exposure, and peak years of the cycle correspond to observed peaks in sea lions stranding with leptospirosis. Seroprevalence in yearling sea lions is strongly correlated with annual changes in high-titer seroprevalence for the whole population, and indicates on-going exposure to serovar Pomona between outbreak years; this finding is consistent with earlier studies reporting continued stranding and death due to leptospirosis in non-outbreak years [18, 19], and inconsistent with expected patterns for an accidental host. Evaluation of individual risk factors reveals that juvenile and subadult animals are at greatest risk for high-titer seropositivity, while adults are at sharply reduced risk.
These observations suggest strongly that leptospirosis is endemic within the sea lion population, and raise the intriguing possibility that repeated epidemics arise from the intrinsic interaction of birth rates and herd immunity, rather than the environmental drivers that are commonly postulated. Younger animals get infected in outbreak years, acquiring high titers that may persist for a year or more, while most adults are immune from previous exposure. The pathogen may persist through off-seasons and non-outbreak years via chronic infections and a low level of on-going transmission, possibly associated with the increased prevalence of asymptomatic seropositivity and low titers during these periods. We emphasize, though, that present data cannot exclude the possibility of on-going contact with another reservoir species. Mathematical models integrating the dynamics of disease transmission and immunity with sea lion demographics, combined with further data collection, are essential to clarify this issue.
Live-stranded marine mammals are a biased sample of the wild population, over-representing sick and weak individuals, so seroprevalence in stranded individuals may exceed the true population value. We addressed this bias by providing alternate seroprevalence estimates based on a reduced dataset excluding clinical leptospirosis cases, but this approach may yield underestimates during outbreaks if a substantial proportion of infected animals do not come ashore. Of over 200,000 sea lions breeding off the California coast , just a few hundred leptospirosis cases strand and are admitted to rehabilitation during a typical outbreak year . Given peak seroprevalence estimates >50%, it appears that many infected animals do not strand. Serosurveillance of free-ranging sea lions is crucial to determine how the patterns reported here scale to the population level.
Data from sea lions stranded in southern California showed a general trend of lower seroprevalence than was found in central and northern California, and, intriguingly, there is no evidence of the 2004 outbreak in data from the southern range. All California sea lions in the eastern Pacific Ocean breed on rookery islands off the coast of southern California and the Baja peninsula, so animals stranding in different regions of California are thought to be drawn from a single population. Leptospirosis strandings (and high-titer seropositivity) peak during July to November , when sea lions migrate northward following the breeding season to forage off central and northern California, or points further north. It is unknown whether this timing is coincidental or leptospirosis transmission (or exposure) is aided by environmental factors in the northern range. Male sea lions migrate further north than females, and in greater numbers, while breeding females remain closer to the rookeries to nurse pups. This difference in migratory behavior may play a role in the observed sex difference in leptospirosis incidence, although similar sex differences have been observed in other species including humans and are not easily explained [13, 43]. Data presented here suggest that leptospirosis incidence is lower among animals remaining in southern California, but increased sampling of stranded and wild-caught individuals is needed to confirm this pattern.
The predominance of high titers among seropositive sea lions (also reported by Colagross-Schouten ) indicates that most animals had been exposed recently before stranding. Yet the time course of titer decay for this host-serovar interaction is unknown, so we assembled evidence to assess the duration of high MAT titers in sea lions. Population-level changes in seroprevalence suggest that approximately 69% of high-titer individuals lose their high titer in a year without re-exposure to the pathogen (but note the broad 95% CI, 0.06–100%). This is consistent with observed titer distributions in sea lions, which indicate that ≥ 32% of individuals should lose their high titers after 8 antibody half-lives, but more precise predictions cannot be derived from titer distributions because the majority of sea lion titers were positive at the highest dilution measured. Maintenance of high MAT titers for several years is not reported in experimental infection studies, which rarely last that long, but has been reported for humans following severe infections [1, 21–23]. MAT titer half-life for sea lions in rehabilitation was estimated crudely to have upper bound 20 (19–22) days, lower than the conventional half-life of 23–25 days for IgG antibodies. While this difference could be attributed to numerous factors, including that MAT titers reflect both IgM and IgG levels  and antibiotic therapy may reduce titer duration , it is important to note the small sample size underlying the estimate, and the well-established finding that human MAT decay rates vary substantially [21–23]. Titer distributions in stranded sea lions are qualitatively consistent with gradual antibody decay following exposure, but intermediate titers (from 1:3200 to 1:51200) appear less commonly than a simple exponential decay model would predict. Longitudinal titers from individuals recovering from acute infection are required to characterize the true rate of antibody decay from high levels. The possible role of chronic shedders, in maintaining their own low-titer seropositivity and in boosting the antibody responses of others, requires investigation.