Discussion
Using a large long-term dataset including over 3,400 individuals and spanning 27 years, we report the spread of TB in wild meerkats, and quantify the extent of TB exposure, clinical TB prevalence and TB-related mortality. We show that exposure to TB rose to over 50% within approximately eight years after first detection within the population and increased to up to over 90%. Rates of clinical disease and mortality over the same period peaked at around 25% and 6%, respectively, suggesting a degree of resistance to the pathogen. TB prevalence varied strongly between the years, with over one quarter of the population displaying clinical signs in some years. TB prevalence reported this study is comparable with those reported from other well-studied species (~ 12 % for European badgers (Meles meles ) to ~ 32% for red deer (Cervus elaphus ) and wild boar (Sus scrofa ), see Reis et al., 2021), both with regard to overall (16.2%) and annual prevalence. Previous studies, using diagnostic tools on subset of the study population to detect TB reported prevalence between 24% (Drewe, 2010) and up to 82.4% of individuals of exposed groups (Clarke et al., 2016), implying that by using clinical signs, the true extent ofMycobacterium infection prevalence is underestimated.
In line with previous studies, we find TB contributing strongly to meerkat mortality, both on the individual and group level (Patterson et al., 2017; Duncan et al., 2021). At 11.6%, individual TB related mortality is almost twice as high as previously reported in the same population (Patterson et al., 2017), and comparable with estimated annual mortality of mongooses infected with M. mungi (Fairbanks et al., 2014). Most individuals (71.7%) with clinical signs were confirmed to have died of or with TB, yet given the irreversible nature of TB progression, the disease was likely a contributing factor in the death of diseased individuals dying of other causes. As many infected individuals likely die before progressing to clinical stages, subclinical infections are known to increase mortality risk (Patterson et al., 2021), and the impact of Mycobacterium infections on the population is likely even higher than reported here.
We observe a high extend of variation of TB susceptibility, resistance and progression patterns across the study population. Only ~22% of exposed individuals progress to clinical TB, on average within 1.4. years of exposure. Our findings confirm the generally long latent or subclinical period of M. suricattaeinfections(Drewe, Dean et al., 2009; Donadio et al., 2022), with individuals developing TB signs as long as 8 years past first exposure. As infection occur on average 1 year before the onset of clinical signs (Donadio et al. 2022), most exposed individuals are likely infected for most of the time between exposure and clinical TB manifestation. The rate of individuals not susceptible to TB has been estimated at around 25.8% in a recent study (Donadio et al. 2022), implying that ~ 50% of exposed individuals are infected without displaying overt symptoms. This finding is comparable to results in badgers, where up to 80% of infected individuals do not present visible TB lesions (Gallagher and Clifton-Hadley, 2000).
After onset of clinical TB, meerkats in our study died on average within ~ 6.6 months, confirming the rapid progression to terminal stages reported by previous studies of the same population (Patterson et al., 2021; Donadio et al., 2022). This pattern of prolonged subclinical or latent infection with rapid progression upon onset of clinical signs is a common feature of wildlife TB (Alexander et al., 2010; Tomlinson et al., 2013; Spickler, 2019). Individuals survived for up to 7.5 years post first TB signs, suggesting factors facilitating natural TB resistance. The capacity of some individuals to survive TB for a long period is another common feature of wildlife MTC pathogen infections (Ezenwa et al., 2010; Tomlinson et al., 2013). Paradoxically, individuals eventually developing TB signs die at older ages than individuals that never proceed to clinical TB stages, a phenomenon most likely attributable to the long latent period compared to meerkat life expectancy. Baseline mortality rates in meerkats are high, with subordinates suffering increased mortality risk upon evictions (Cram et al., 2018), so while KMP meerkats can live up to ~12 years, median life expectancy is only 2.3 years (Drewe, 2009), making death of infected individuals prior to clinical manifestation of TB a likely occurrence.
The origin of M. suricattae in the study population and when it first emerged is currently unclear. Furthermore, whether meerkats are the original host, or the pathogen was transmitted from another, yet unknown reservoir species, is not clear to date (Alexander et al., 2010; Parsons et al., 2013). While the disease was probably present in the study population from the beginning of data recording, and exposure as well as prevalence are likely underestimated in the first years of the long-term project, clinical TB is a highly conspicuous and easily recognizable disease, allowing the conclusion that the rapid increase in detected cases after the late 1990s is reflective of increased disease prevalence and transmission rather than an artifact of observation bias. This conclusion is also supported by the observation that both bovine and non-bovine TB seems to become increasingly prevalent in southern Africa (Michel et al., 2006; Alexander et al., 2010; Tanner et al., 2015; Parsons et al., 2019). Originally, inter-species transmission ofM. bovis was suspected to cause the TB outbreaks in meerkats (Drewe, Dean et al., 2009; Drewe, Foote et al., 2009) before identification of M. suricattae (Parsons et al., 2013, 2019), which is now considered to be endemic in meerkats (Patterson et al., 2022).
The mechanisms underlying this increased TB prevalence and transmission are likely complex and multi-faceted, and their detailed discussion is beyond the scope of this study. However, based on our findings and previous research, we can identify factors that likely contributed to the rapid spread of TB, both inherent to the host-pathogen system and external factors, and discuss the implication of the establishment of TB within the population. Even though clinical TB is highly contagious, there are no obvious behavioural defenses against TB transmission in meerkats: Banded mongooses (Mungos mungo ), which are closely related to meerkats, apparently do not avoid TB affected conspecifics (Fairbanks et al., 2015), and there is no evidence for avoidance behaviour in meerkats to date. Additionally, subclinically infected individuals have been shown to shed M. suricattae via their faeces (Donadio et al., 2022) and thus might be infectious and facilitate transmission, as observed in badgers (Graham et al., 2013; Tomlinson et al., 2013). Both factors could favour spread of TB within a susceptible population. Both within and between group social contact patterns are well established as contributing factors to TB transmission in social mammals (Drewe, 2010; Weber et al., 2013), and in meerkats in particular, migrating males have been implicated to transmit TB between groups (Duncan et al., 2021; Paniw et al., 2022). Consequently, long subclinical infection periods, limitations in behaviourally avoiding TB exposure, and frequent social contacts can facilitate rapid TB transmission within a population based on high levels of exposure.
Transmission can further be facilitated by increased susceptibility to a pathogen. Adverse climate conditions have been suggested to exacerbate the negative effects of TB on individuals and populations (Dwyer et al., 2020; Paniw et al., 2022), potentially indicative of such increased susceptibility to TB of individuals affected by environmental stressors. In the study population, above average temperatures increasingly occurred after the early 2000s and correlate with clinical TB occurrence (Paniw et al., 2022). Both, adverse climate conditions and clinical TB reduce meerkat survival and can lead to group failure, particularly of small groups (Duncan et al., 2021; Paniw et al., 2022), which can lead to higher social mobility, as remnant individuals form new groups or immigrate into other groups. With immigration increasing the risk of TB transmission into previously TB-free groups, these may become more vulnerable to adverse environmental conditions and group extinction once individuals progress to clinical TB and the group suffers from TB related mortality (Duncan et al., 2021; Paniw et al., 2022). Thus, the negative effects of climate change and TB emergence can enforce each other, facilitating TB transmission throughout the study population and affecting population dynamics. Potentially, the effect of M. suricattae infections transcends meerkats and has implications for entire eco-systems, based on the high inter-species transmissibility of MTC pathogens and a wide TB presence in South African mammals (Hlokwe et al., 2014; Clarke et al., 2016; Parsons et al., 2019). Predation is one of the main causes of meerkat mortality (~25%, NMK, unpublished data), so meerkat predators are likely to become exposed toM. suricattae via infected prey, potentially facilitating transmission via ingestion. This possibility highlights the need for detailed and systematic surveillance studies to understand the impact of TB on not only single species, but entire ecosystems.
Our study is based on purely observational data and thus not suitable to investigate determinants of TB susceptibility, resistance and progression. Individuals differ strongly in how they are affected by TB, and the high level of exposed but never clinically ill individuals is suggestive of non-susceptible individuals within the population. Future studies should investigate the impact of hosts immune genetics and responses ( Ezenwa and Jolles, 2015; Ezenwa et al., 2021; Jolma et al., 2021; Marjamäki et al., 2021) in explaining the variation in TB susceptibility, resistance and progression. Furthermore, assessing for effects of pathogen-mediated selection on meerkat population genomics and risk of co-infections will be highly informative furthering our understanding of the effect of TB on meerkat ecology and evolution.