Rapid Evolution of Resistance and Tolerance Leads to Variable Host Recoveries following Disease-Induced Declines.

AbstractRecoveries of populations that have suffered severe disease-induced declines are being observed across disparate taxa. Yet we lack theoretical understanding of the drivers and dynamics of recovery in host populations and communities impacted by infectious disease. Motivated by disease-induced declines and nascent recoveries in amphibians, we developed a model to ask the following question: How does the rapid evolution of different host defense strategies affect the transient recovery trajectories of hosts following pathogen invasion and disease-induced declines? We found that while host life history is predictably a major driver of variability in population recovery trajectories (including declines and recoveries), populations that use different host defense strategies (i.e., tolerance, avoidance resistance, and intensity-reduction resistance) experience notably different recoveries. In single-species host populations, populations evolving tolerance recovered on average four times slower than populations evolving resistance. Moreover, while populations using avoidance resistance strategies had the fastest potential recovery rates, these populations could get trapped in long transient states at low abundance prior to recovery. In contrast, the recovery of populations evolving intensity-reduction resistance strategies were more consistent across ecological contexts. Overall, host defense strategies strongly affect the transient dynamics of population recovery and may affect the ultimate fate of real populations recovering from disease-induced declines.

A time-since-infection model for populations with two pathogens.

The pioneering work of Kermack and McKendrick (1927, 1932, 1933) is now most known for introducing the SIR model, which divides a population into discrete compartments for susceptible, infected and removed individuals. The SIR model is the archetype of widely used compartmental models for epidemics. It is sometimes forgotten, that Kermack and McKendrick introduced the SIR model as a special case of a more general framework. This general framework distinguishes individuals not only by whether they are susceptible, infected or removed, but additionally tracks the time passed since they got infected. Such time-since-infection models can mechanistically link within-host dynamics to the population level. This allows the models to account for more details of the disease dynamics, such as delays of infectiousness and symptoms during the onset of an infection. Details like this can be vital for interpreting epidemiological data. The time-since-infection framework was originally formulated for a host population with a single pathogen. However, the interactions of multiple pathogens within hosts and within a population can be crucial for understanding the severity and spread of diseases. Current models for multiple pathogens mostly rely on compartmental models. While such models are relatively easy to set up, they do not have the same mechanistic underpinning as time-since-infection models. To approach this gap of connecting within-host dynamics of multiple pathogens to the population level, we here extend the time-since-infection framework of Kermack and McKendrick for two pathogens. We derive formulas for the basic reproduction numbers in the system. Those numbers determine whether a pathogen can invade a population, potentially depending on whether the other pathogen is present or not. We then demonstrate use of the framework by setting up a simple within-host model that we connect to the population model. The example illustrates the context-specific information required for this type of model, and shows how the system can be simulated numerically. We verify that the formulas for the basic reproduction numbers correctly specify the invasibility conditions.

Host density has limited effects on pathogen invasion, disease-induced declines and within-host infection dynamics across a landscape of disease.

1. Host density is hypothesized to be a major driver of variability in the responses and outcomes of wildlife populations following pathogen invasion. While the effects of host density on pathogen transmission have been extensively studied, these studies are dominated by theoretical analyses and small-scale experiments. This focus leads to an incomplete picture regarding how host density drives observed variability in disease outcomes in the field. 2. Here, we leveraged a dataset of hundreds of replicate amphibian populations that varied by orders of magnitude in host density. We used these data to test the effects of host density on three outcomes following the arrival of the amphibian-killing fungal pathogen Batrachochytrium dendrobatidis (Bd): the probability that Bd successfully invaded a host population and led to a pathogen outbreak, the magnitude of the host population-level decline following an outbreak and within-host infection dynamics that drive population-level outcomes in amphibian-pathogen systems. 3. Based on previous small-scale transmission experiments, we expected that populations with higher densities would be more likely to experience Bd outbreaks and would suffer larger proportional declines following outbreaks. To test these predictions, we developed and fitted a Hidden Markov Model that accounted for imperfectly observed disease outbreak states in the amphibian populations we surveyed. 4. Contrary to our predictions, we found minimal effects of host density on the probability of successful Bd invasion, the magnitude of population decline following Bd invasion and the dynamics of within-host infection intensity. Environmental conditions, such as summer temperature, winter severity and the presence of pathogen reservoirs, were more predictive of variability in disease outcomes. 5. Our results highlight the limitations of extrapolating findings from small-scale transmission experiments to observed disease trajectories in the field and provide strong evidence that variability in host density does not necessarily drive variability in host population responses following pathogen arrival. In an applied context, we show that feedbacks between host density and disease will not necessarily affect the success of reintroduction efforts in amphibian-Bd systems of conservation concern.

Cryptic diversity of a widespread global pathogen reveals expanded threats to amphibian conservation.

Biodiversity loss is one major outcome of human-mediated ecosystem disturbance. One way that humans have triggered wildlife declines is by transporting disease-causing agents to remote areas of the world. Amphibians have been hit particularly hard by disease due in part to a globally distributed pathogenic chytrid fungus (Batrachochytrium dendrobatidis [Bd]). Prior research has revealed important insights into the biology and distribution of Bd; however, there are still many outstanding questions in this system. Although we know that there are multiple divergent lineages of Bd that differ in pathogenicity, we know little about how these lineages are distributed around the world and where lineages may be coming into contact. Here, we implement a custom genotyping method for a global set of Bd samples. This method is optimized to amplify and sequence degraded DNA from noninvasive skin swab samples. We describe a divergent lineage of Bd, which we call BdASIA3, that appears to be widespread in Southeast Asia. This lineage co-occurs with the global panzootic lineage (BdGPL) in multiple localities. Additionally, we shed light on the global distribution of BdGPL and highlight the expanded range of another lineage, BdCAPE. Finally, we argue that more monitoring needs to take place where Bd lineages are coming into contact and where we know little about Bd lineage diversity. Monitoring need not use expensive or difficult field techniques but can use archived swab samples to further explore the history-and predict the future impacts-of this devastating pathogen.

Mechanisms underlying host persistence following amphibian disease emergence determine appropriate management strategies.

Emerging infectious diseases have caused many species declines, changes in communities and even extinctions. There are also many species that persist following devastating declines due to disease. The broad mechanisms that enable host persistence following declines include evolution of resistance or tolerance, changes in immunity and behaviour, compensatory recruitment, pathogen attenuation, environmental refugia, density-dependent transmission and changes in community composition. Here we examine the case of chytridiomycosis, the most important wildlife disease of the past century. We review the full breadth of mechanisms allowing host persistence, and synthesise research on host, pathogen, environmental and community factors driving persistence following chytridiomycosis-related declines and overview the current evidence and the information required to support each mechanism. We found that for most species the mechanisms facilitating persistence have not been identified. We illustrate how the mechanisms that drive long-term host population dynamics determine the most effective conservation management strategies. Therefore, understanding mechanisms of host persistence is important because many species continue to be threatened by disease, some of which will require intervention. The conceptual framework we describe is broadly applicable to other novel disease systems.

Integrating Infection Intensity into Within- and Between-Host Pathogen Dynamics: Implications for Invasion and Virulence Evolution.

AbstractInfection intensity can dictate disease outcomes but is typically ignored when modeling infection dynamics of microparasites (e.g., bacteria, virus, and fungi). However, for a number of pathogens of wildlife typically categorized as microparasites, accounting for infection intensity and within-host infection processes is critical for predicting population-level responses to pathogen invasion. Here, we develop a modeling framework we refer to as reduced-dimension host-parasite integral projection models (reduced IPMs) that we use to explore how within-host infection processes affect the dynamics of pathogen invasion and virulence evolution. We find that individual-level heterogeneity in pathogen load-a nearly ubiquitous characteristic of host-parasite interactions that is rarely considered in models of microparasites-generally reduces pathogen invasion probability and dampens virulence-transmission trade-offs in host-parasite systems. The latter effect likely contributes to widely predicted virulence-transmission trade-offs being difficult to observe empirically. Moreover, our analyses show that intensity-dependent host mortality does not always induce a virulence-transmission trade-off, and systems with steeper than linear relationships between pathogen intensity and host mortality rate are significantly more likely to exhibit these trade-offs. Overall, reduced IPMs provide a useful framework to expand our theoretical and data-driven understanding of how within-host processes affect population-level disease dynamics.

Divergent regional evolutionary histories of a devastating global amphibian pathogen.

Emerging infectious diseases are a pressing threat to global biological diversity. Increased incidence and severity of novel pathogens underscores the need for methodological advances to understand pathogen emergence and spread. Here, we use genetic epidemiology to test, and challenge, key hypotheses about a devastating zoonotic disease impacting amphibians globally. Using an amplicon-based sequencing method and non-invasive samples we retrospectively explore the history of the fungal pathogen Batrachochytrium dendrobatidis (Bd) in two emblematic amphibian systems: the Sierra Nevada of California and Central Panama. The hypothesis in both regions is the hypervirulent Global Panzootic Lineage of Bd (BdGPL) was recently introduced and spread rapidly in a wave-like pattern. Our data challenge this hypothesis by demonstrating similar epizootic signatures can have radically different underlying evolutionary histories. In Central Panama, our genetic data confirm a recent and rapid pathogen spread. However, BdGPL in the Sierra Nevada has remarkable spatial structuring, high genetic diversity and a relatively older history inferred from time-dated phylogenies. Thus, this deadly pathogen lineage may have a longer history in some regions than assumed, providing insights into its origin and spread. Overall, our results highlight the importance of integrating observed wildlife die-offs with genetic data to more accurately reconstruct pathogen outbreaks.

Disease hotspots or hot species? Infection dynamics in multi-host metacommunities controlled by species identity, not source location.

Pathogen persistence in host communities is influenced by processes operating at the individual host to landscape-level scale, but isolating the relative contributions of these processes is challenging. We developed theory to partition the influence of host species, habitat patches and landscape connectivity on pathogen persistence within metacommunities of hosts and pathogens. We used this framework to quantify the contributions of host species composition and habitat patch identity on the persistence of an amphibian pathogen across the landscape. By sampling over 11 000 hosts of six amphibian species, we found that a single host species could maintain the pathogen in 91% of observed metacommunities. Moreover, this dominant maintenance species contributed, on average, twice as much to landscape-level pathogen persistence compared to the most influential source patch in a metacommunity. Our analysis demonstrates substantial inequality in how species and patches contribute to pathogen persistence, with important implications for targeted disease management.

Fungal infection alters the selection, dispersal and drift processes structuring the amphibian skin microbiome.

Symbiotic microbial communities are important for host health, but the processes shaping these communities are poorly understood. Understanding how community assembly processes jointly affect microbial community composition is limited because inflexible community models rely on rejecting dispersal and drift before considering selection. We developed a flexible community assembly model based on neutral theory to ask: How do dispersal, drift and selection concurrently affect the microbiome across environmental gradients? We applied this approach to examine how a fungal pathogen affected the assembly processes structuring the amphibian skin microbiome. We found that the rejection of neutrality for the amphibian microbiome across a fungal gradient was not strictly due to selection processes, but was also a result of species-specific changes in dispersal and drift. Our modelling framework brings the qualitative recognition that niche and neutral processes jointly structure microbiomes into quantitative focus, allowing for improved predictions of microbial community turnover across environmental gradients.

Stepping into the past to conserve the future: Archived skin swabs from extant and extirpated populations inform genetic management of an endangered amphibian.

Moving animals on a landscape through translocations and reintroductions is an important management tool used in the recovery of endangered species, particularly for the maintenance of population genetic diversity and structure. Management of imperiled amphibian species rely heavily on translocations and reintroductions, especially for species that have been brought to the brink of extinction by habitat loss, introduced species, and disease. One striking example of amphibian declines and associated management efforts is in California's Sequoia and Kings Canyon National Parks with the mountain yellow-legged frog species complex (Rana sierrae/muscosa). Mountain yellow-legged frogs have been extirpated from more than 93% of their historic range, and limited knowledge of their population genetics has made long-term conservation planning difficult. To address this, we used 598 archived skin swabs from both extant and extirpated populations across 48 lake basins to generate a robust Illumina-based nuclear amplicon data set. We found that samples grouped into three main genetic clusters, concordant with watershed boundaries. We also found evidence for historical gene flow across watershed boundaries with a north-to-south axis of migration. Finally, our results indicate that genetic diversity is not significantly different between populations with different disease histories. Our study offers specific management recommendations for imperiled mountain yellow-legged frogs and, more broadly, provides a population genetic framework for leveraging minimally invasive samples for the conservation of threatened species.

Disease's hidden death toll: Using parasite aggregation patterns to quantify landscape-level host mortality in a wildlife system.

World-wide, infectious diseases represent a major source of mortality in humans and livestock. For wildlife populations, disease-induced mortality is likely even greater, but remains notoriously difficult to estimate-especially for endemic infections. Approaches for quantifying wildlife mortality due to endemic infections have historically been limited by an inability to directly observe wildlife mortality in nature. Here we address a question that can rarely be answered for endemic pathogens of wildlife: what are the population- and landscape-level effects of infection on host mortality? We combined laboratory experiments, extensive field data and novel mathematical models to indirectly estimate the magnitude of mortality induced by an endemic, virulent trematode parasite (Ribeiroia ondatrae) on hundreds of amphibian populations spanning four native species. We developed a flexible statistical model that uses patterns of aggregation in parasite abundance to infer host mortality. Our model improves on previous approaches for inferring host mortality from parasite abundance data by (i) relaxing restrictive assumptions on the timing of host mortality and sampling, (ii) placing all mortality inference within a Bayesian framework to better quantify uncertainty and (iii) accommodating data from laboratory experiments and field sampling to allow for estimates and comparisons of mortality within and among host populations. Applying our approach to 301 amphibian populations, we found that trematode infection was associated with an average of between 13% and 40% population-level mortality. For three of the four amphibian species, our models predicted that some populations experienced >90% mortality due to infection, leading to mortality of thousands of amphibian larvae within a pond. At the landscape scale, the total number of amphibians predicted to succumb to infection was driven by a few high mortality sites, with fewer than 20% of sites contributing to greater than 80% of amphibian mortality on the landscape. The mortality estimates in this study provide a rare glimpse into the magnitude of effects that endemic parasites can have on wildlife populations and our theoretical framework for indirectly inferring parasite-induced mortality can be applied to other host-parasite systems to help reveal the hidden death toll of pathogens on wildlife hosts.

Probiotics Modulate a Novel Amphibian Skin Defense Peptide That Is Antifungal and Facilitates Growth of Antifungal Bacteria.

Probiotics can ameliorate diseases of humans and wildlife, but the mechanisms remain unclear. Host responses to interventions that change their microbiota are largely uncharacterized. We applied a consortium of four natural antifungal bacteria to the skin of endangered Sierra Nevada yellow-legged frogs, Rana sierrae, before experimental exposure to the pathogenic fungus Batrachochytrium dendrobatidis (Bd). The probiotic microbes did not persist, nor did they protect hosts, and skin peptide sampling indicated immune modulation. We characterized a novel skin defense peptide brevinin-1Ma (FLPILAGLAANLVPKLICSITKKC) that was downregulated by the probiotic treatment. Brevinin-1Ma was tested against a range of amphibian skin cultures and found to inhibit growth of fungal pathogens Bd and B. salamandrivorans, but enhanced the growth of probiotic bacteria including Janthinobacterium lividum, Chryseobacterium ureilyticum, Serratia grimesii, and Pseudomonas sp. While commonly thought of as antimicrobial peptides, here brevinin-1Ma showed promicrobial function, facilitating microbial growth. Thus, skin exposure to probiotic bacterial cultures induced a shift in skin defense peptide profiles that appeared to act as an immune response functioning to regulate the microbiome. In addition to direct microbial antagonism, probiotic-host interactions may be a critical mechanism affecting disease resistance.

Large-scale recovery of an endangered amphibian despite ongoing exposure to multiple stressors.

Amphibians are one of the most threatened animal groups, with 32% of species at risk for extinction. Given this imperiled status, is the disappearance of a large fraction of the Earth's amphibians inevitable, or are some declining species more resilient than is generally assumed? We address this question in a species that is emblematic of many declining amphibians, the endangered Sierra Nevada yellow-legged frog (Rana sierrae). Based on >7,000 frog surveys conducted across Yosemite National Park over a 20-y period, we show that, after decades of decline and despite ongoing exposure to multiple stressors, including introduced fish, the recently emerged disease chytridiomycosis, and pesticides, R. sierrae abundance increased sevenfold during the study and at a rate of 11% per year. These increases occurred in hundreds of populations throughout Yosemite, providing a rare example of amphibian recovery at an ecologically relevant spatial scale. Results from a laboratory experiment indicate that these increases may be in part because of reduced frog susceptibility to chytridiomycosis. The disappearance of nonnative fish from numerous water bodies after cessation of stocking also contributed to the recovery. The large-scale increases in R. sierrae abundance that we document suggest that, when habitats are relatively intact and stressors are reduced in their importance by active management or species' adaptive responses, declines of some amphibians may be partially reversible, at least at a regional scale. Other studies conducted over similarly large temporal and spatial scales are critically needed to provide insight and generality about the reversibility of amphibian declines at a global scale.

Of poisons and parasites-the defensive role of tetrodotoxin against infections in newts.

Classical research on animal toxicity has focused on the role of toxins in protection against predators, but recent studies suggest these same compounds can offer a powerful defense against parasites and infectious diseases. Newts in the genus Taricha are brightly coloured and contain the potent neurotoxin, tetrodotoxin (TTX), which is hypothesized to have evolved as a defense against vertebrate predators such as garter snakes. However, newt populations often vary dramatically in toxicity, which is only partially explained by predation pressure. The primary aim of this study was to evaluate the relationships between TTX concentration and infection by parasites. By systematically assessing micro- and macroparasite infections among 345 adult newts (sympatric populations of Taricha granulosa and T. torosa), we detected 18 unique taxa of helminths, fungi, viruses and protozoans. For both newt species, per-host concentrations of TTX, which varied from undetectable to >60 µg/cm2 skin, negatively predicted overall parasite richness as well as the likelihood of infection by the chytrid fungus, Batrachochytrium dendrobatidis, and ranavirus. No such effect was found on infection load among infected hosts. Despite commonly occurring at the same wetlands, T. torosa supported higher parasite richness and average infection load than T. granulosa. Host body size and sex (females > males) tended to positively predict infection levels in both species. For hosts in which we quantified leucocyte profiles, total white blood cell count correlated positively with both parasite richness and total infection load. By coupling data on host toxicity and infection by a broad range of micro- and macroparasites, these results suggest that-alongside its effects on predators-tetrodotoxin may help protect newts against parasitic infections, highlighting the importance of integrative research on animal chemistry, immunological defenses and natural enemy ecology.

Emerging fungal threats to animal, plant and ecosystem health.

The past two decades have seen an increasing number of virulent infectious diseases in natural populations and managed landscapes. In both animals and plants, an unprecedented number of fungal and fungal-like diseases have recently caused some of the most severe die-offs and extinctions ever witnessed in wild species, and are jeopardizing food security. Human activity is intensifying fungal disease dispersal by modifying natural environments and thus creating new opportunities for evolution. We argue that nascent fungal infections will cause increasing attrition of biodiversity, with wider implications for human and ecosystem health, unless steps are taken to tighten biosecurity worldwide.

Occurrence of Batrachochytrium dendrobatidis in anurans of the Mediterranean region of Baja California, México.

Chytridiomycosis is caused by the fungal pathogen Batrachochytrium dendrobatidis (Bd) and is regarded as one of the most significant threats to global amphibian populations. In México, Bd was first reported in 2003 and has now been documented in 13 states. We visited 33 localities and swabbed 199 wild-caught anurans from 7 species (5 native, 2 exotic) across the Mediterranean region of the state of Baja California. Using quantitative PCR, Bd was detected in 94 individuals (47.2% of samples) at 25 of the 33 survey localities for 5 native and 1 exotic frog species. The exotic Xenopus laevis was the only species that tested completely negative for Bd. We found that remoteness, distance to agricultural land, and elevation were the best positive predictors of Bd presence. These are the first Bd-positive results for the state of Baja California, and its presence should be regarded as an additional conservation threat to the region's native frog species.

Resistance, tolerance and environmental transmission dynamics determine host extinction risk in a load-dependent amphibian disease.

While disease-induced extinction is generally considered rare, a number of recently emerging infectious diseases with load-dependent pathology have led to extinction in wildlife populations. Transmission is a critical factor affecting disease-induced extinction, but the relative importance of transmission compared to load-dependent host resistance and tolerance is currently unknown. Using a combination of models and experiments on an amphibian species suffering extirpations from the fungal pathogen Batrachochytrium dendrobatidis (Bd), we show that while transmission from an environmental Bd reservoir increased the ability of Bd to invade an amphibian population and the extinction risk of that population, Bd-induced extinction dynamics were far more sensitive to host resistance and tolerance than to Bd transmission. We demonstrate that this is a general result for load-dependent pathogens, where non-linear resistance and tolerance functions can interact such that small changes in these functions lead to drastic changes in extinction dynamics.

Epidemic and endemic pathogen dynamics correspond to distinct host population microbiomes at a landscape scale.

Infectious diseases have serious impacts on human and wildlife populations, but the effects of a disease can vary, even among individuals or populations of the same host species. Identifying the reasons for this variation is key to understanding disease dynamics and mitigating infectious disease impacts, but disentangling cause and correlation during natural outbreaks is extremely challenging. This study aims to understand associations between symbiotic bacterial communities and an infectious disease, and examines multiple host populations before or after pathogen invasion to infer likely causal links. The results show that symbiotic bacteria are linked to fundamentally different outcomes of pathogen infection: host-pathogen coexistence (endemic infection) or host population extirpation (epidemic infection). Diversity and composition of skin-associated bacteria differed between populations of the frog, Rana sierrae, that coexist with or were extirpated by the fungal pathogen, Batrachochytrium dendrobatidis (Bd). Data from multiple populations sampled before or after pathogen invasion were used to infer cause and effect in the relationship between the fungal pathogen and symbiotic bacteria. Among host populations, variation in the composition of the skin microbiome was most strongly predicted by pathogen infection severity, even in analyses where the outcome of infection did not vary. This result suggests that pathogen infection shapes variation in the skin microbiome across host populations that coexist with or are driven to extirpation by the pathogen. By contrast, microbiome richness was largely unaffected by pathogen infection intensity, but was strongly predicted by geographical region of the host population, indicating the importance of environmental or host genetic factors in shaping microbiome richness. Thus, while both richness and composition of the microbiome differed between endemic and epidemic host populations, the underlying causes are most likely different: pathogen infection appears to shape microbiome composition, while microbiome richness was less sensitive to pathogen-induced disturbance. Because higher richness was correlated with host persistence in the presence of Bd, and richness appeared relatively stable to Bd infection, microbiome richness may contribute to disease resistance, although the latter remains to be directly tested.

When can we infer mechanism from parasite aggregation? A constraint-based approach to disease ecology.

Few hosts have many parasites while many hosts have few parasites. This axiom of macroparasite aggregation is so pervasive it is considered a general law in disease ecology, with important implications for the dynamics of host-parasite systems. Because of these dynamical implications, a significant amount of work has explored both the various mechanisms leading to parasite aggregation patterns and how to infer mechanism from these patterns. However, as many disease mechanisms can produce similar aggregation patterns, it is not clear whether aggregation itself provides any additional information about mechanism. Here we apply a "constraint-based" approach developed in macroecology that allows us to explore whether parasite aggregation contains any additional information beyond what is provided by mean parasite load. We tested two constraint-based null models, both of which were constrained on the total number of parasites P and hosts H found in a sample, using data from 842 observed amphibian host-trematode parasite distributions. We found that constraint-based models captured ~85% of the observed variation in host-parasite distributions, suggesting that the constraints P and H contain much of the information about the shape of the host-parasite distribution. However, we also found that extending the constraint-based null models can identify the potential role of known aggregating mechanisms (such as host heterogeneity) and disaggregating mechanisms (such as parasite-induced host mortality) in constraining host-parasite distributions. Thus, by providing robust null models, constraint-based approaches can help guide investigations aimed at detecting biological processes that directly affect parasite aggregation above and beyond those that indirectly affect aggregation through P and H.

Modeling Virus Coinfection to Inform Management of Maize Lethal Necrosis in Kenya.

Maize lethal necrosis (MLN) has emerged as a serious threat to food security in sub-Saharan Africa. MLN is caused by coinfection with two viruses, Maize chlorotic mottle virus and a potyvirus, often Sugarcane mosaic virus. To better understand the dynamics of MLN and to provide insight into disease management, we modeled the spread of the viruses causing MLN within and between growing seasons. The model allows for transmission via vectors, soil, and seed, as well as exogenous sources of infection. Following model parameterization, we predict how management affects disease prevalence and crop performance over multiple seasons. Resource-rich farmers with large holdings can achieve good control by combining clean seed and insect control. However, crop rotation is often required to effect full control. Resource-poor farmers with smaller holdings must rely on rotation and roguing, and achieve more limited control. For both types of farmer, unless management is synchronized over large areas, exogenous sources of infection can thwart control. As well as providing practical guidance, our modeling framework is potentially informative for other cropping systems in which coinfection has devastating effects. Our work also emphasizes how mathematical modeling can inform management of an emerging disease even when epidemiological information remains scanty. [Formula: see text] Copyright © 2017 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .