The Hidden Hand of Asymptomatic Infection Hinders Control of Neglected Tropical Diseases: A Modeling Analysis.

BACKGROUND: Neglected tropical diseases are responsible for considerable morbidity and mortality in low-income populations. International efforts have reduced their global burden, but transmission is persistent and case-finding-based interventions rarely target asymptomatic individuals. METHODS: We develop a generic mathematical modeling framework for analyzing the dynamics of visceral leishmaniasis in the Indian sub-continent (VL), gambiense sleeping sickness (gHAT), and Chagas disease and use it to assess the possible contribution of asymptomatics who later develop disease (pre-symptomatics) and those who do not (non-symptomatics) to the maintenance of infection. Plausible interventions, including active screening, vector control, and reduced time to detection, are simulated for the three diseases. RESULTS: We found that the high asymptomatic contribution to transmission for Chagas and gHAT and the apparently high basic reproductive number of VL may undermine long-term control. However, the ability to treat some asymptomatics for Chagas and gHAT should make them more controllable, albeit over relatively long time periods due to the slow dynamics of these diseases. For VL, the toxicity of available therapeutics means the asymptomatic population cannot currently be treated, but combining treatment of symptomatics and vector control could yield a quick reduction in transmission. CONCLUSIONS: Despite the uncertainty in natural history, it appears there is already a relatively good toolbox of interventions to eliminate gHAT, and it is likely that Chagas will need improvements to diagnostics and their use to better target pre-symptomatics. The situation for VL is less clear, and model predictions could be improved by additional empirical data. However, interventions may have to improve to successfully eliminate this disease.

A metapopulation model of social group dynamics and disease applied to Yellowstone wolves.

The population structure of social species has important consequences for both their demography and transmission of their pathogens. We develop a metapopulation model that tracks two key components of a species' social system: average group size and number of groups within a population. While the model is general, we parameterize it to mimic the dynamics of the Yellowstone wolf population and two associated pathogens: sarcoptic mange and canine distemper. In the initial absence of disease, we show that group size is mainly determined by the birth and death rates and the rates at which groups fission to form new groups. The total number of groups is determined by rates of fission and fusion, as well as environmental resources and rates of intergroup aggression. Incorporating pathogens into the models reduces the size of the host population, predominantly by reducing the number of social groups. Average group size responds in more subtle ways: infected groups decrease in size, but uninfected groups may increase when disease reduces the number of groups and thereby reduces intraspecific aggression. Our modeling approach allows for easy calculation of prevalence at multiple scales (within group, across groups, and population level), illustrating that aggregate population-level prevalence can be misleading for group-living species. The model structure is general, can be applied to other social species, and allows for a dynamic assessment of how pathogens can affect social structure and vice versa.

Dietary abundance distributions: Dominance and diversity in vertebrate diets.

Diet composition is among the most important yet least understood dimensions of animal ecology. Inspired by the study of species abundance distributions (SADs), we tested for generalities in the structure of vertebrate diets by characterising them as dietary abundance distributions (DADs). We compiled data on 1167 population-level diets, representing >500 species from six vertebrate classes, spanning all continents and oceans. DADs near-universally (92.5%) followed a hollow-curve shape, with scant support for other plausible rank-abundance-distribution shapes. This strong generality is inherently related to, yet incompletely explained by, the SADs of available food taxa. By quantifying dietary generalisation as the half-saturation point of the cumulative distribution of dietary abundance (sp50, minimum number of foods required to account for 50% of diet), we found that vertebrate populations are surprisingly specialised: in most populations, fewer than three foods accounted for at least half the diet. Variation in sp50 was strongly associated with consumer type, with carnivores being more specialised than herbivores or omnivores. Other methodological (sampling method and effort, taxonomic resolution), biological (body mass, frugivory) and biogeographic (latitude) factors influenced sp50 to varying degrees. Future challenges include identifying the mechanisms underpinning the hollow-curve DAD, its generality beyond vertebrates, and the biological determinants of dietary generalisation.

Development, environmental degradation, and disease spread in the Brazilian Amazon.

The Amazon is Brazil's greatest natural resource and invaluable to the rest of the world as a buffer against climate change. The recent election of Brazil's president brought disputes over development plans for the region back into the spotlight. Historically, the development model for the Amazon has focused on exploitation of natural resources, resulting in environmental degradation, particularly deforestation. Although considerable attention has focused on the long-term global cost of "losing the Amazon," too little attention has focused on the emergence and reemergence of vector-borne diseases that directly impact the local population, with spillover effects to other neighboring areas. We discuss the impact of Amazon development models on human health, with a focus on vector-borne disease risk. We outline policy actions that could mitigate these negative impacts while creating opportunities for environmentally sensitive economic activities.

Spatiotemporal variations in exposure: Chagas disease in Colombia as a case study.

Age-stratified serosurvey data are often used to understand spatiotemporal trends in disease incidence and exposure through estimating the Force-of-Infection (FoI). Typically, median or mean FoI estimates are used as the response variable in predictive models, often overlooking the uncertainty in estimated FoI values when fitting models and evaluating their predictive ability. To assess how this uncertainty impact predictions, we compared three approaches with three levels of uncertainty integration. We propose a performance indicator to assess how predictions reflect initial uncertainty.In Colombia, 76 serosurveys (1980-2014) conducted at municipality level provided age-stratified Chagas disease prevalence data. The yearly FoI was estimated at the serosurvey level using a time-varying catalytic model. Environmental, demographic and entomological predictors were used to fit and predict the FoI at municipality level from 1980 to 2010 across Colombia.A stratified bootstrap method was used to fit the models without temporal autocorrelation at the serosurvey level. The predictive ability of each model was evaluated to select the best-fit models within urban, rural and (Amerindian) indigenous settings. Model averaging, with the 10 best-fit models identified, was used to generate predictions.Our analysis shows a risk of overconfidence in model predictions when median estimates of FoI alone are used to fit and evaluate models, failing to account for uncertainty in FoI estimates. Our proposed methodology fully propagates uncertainty in the estimated FoI onto the generated predictions, providing realistic assessments of both central tendency and current uncertainty surrounding exposure to Chagas disease.

COVID-Clarity demands unification of health and environmental policy.

Spillover of novel pathogens from wildlife to people, such as the virus responsible for the COVID-19 pandemic, is increasing and this trend is most strongly associated with tropical deforestation driven by agricultural expansion. This same process is eroding natural capital, reducing forest-associated health co-benefits, and accelerating climate change. Protecting and promoting tropical forests is one of the most immediate steps we can take to simultaneously mitigate climate change while reducing the risk of future pandemics; however, success in this undertaking will require greater connectivity of policy initiatives from local to global, as well as unification of health and environmental policy.

Host population dynamics in the face of an evolving pathogen.

Interactions between hosts and pathogens are dynamic at both ecological and evolutionary levels. In the resultant 'eco-evolutionary dynamics' ecological and evolutionary processes affect each other. For example, the house finch Haemorhous mexicanus and its recently emerged pathogen, the bacterium Mycoplasma gallisepticum, form a system in which evidence suggests that changes in bacterial virulence through time enhance levels of host immunity in ways that drive the evolution of virulence in an arms race. We use data from two associated citizen science projects in order to determine whether this arms race has had any detectable effect at the population level in the north-eastern United States. We used data from two citizen science projects, based on observations of birds at bird feeders, which provide information on the long-term changes in sizes of aggregations of house finches (host population density), and the probabilities that these house finches have observable disease (disease prevalence). The initial emergence of M. gallisepticum caused a rapid halving of house finch densities; this was then followed by house finch populations remaining stable or slowly declining. Disease prevalence also decreased sharply after the initial emergence and has remained low, although with fluctuations through time. Surprisingly, while initially higher local disease prevalence was found at sites with higher local densities of finches, this relationship has reversed over time. The ability of a vertebrate host species, with a generation time of at least 1 year, to maintain stable populations in the face of evolved higher virulence of a bacterium, with generation times measurable in minutes, suggests that genetic changes in the host are insufficient to explain the observed population-level patterns. We suggest that acquired immunity plays an important role in the observed interaction between house finches and M. gallisepticum.

Investigating the Dynamics of Elk Population Size and Body Mass in a Seasonal Environment Using a Mechanistic Integral Projection Model.

Environmentally mediated changes in body size often underlie population responses to environmental change, yet this is not a universal phenomenon. Understanding when phenotypic change underlies population responses to environmental change is important for obtaining insights and robust predictions of population dynamics in a changing world. We develop a dynamic integral projection model that mechanistically links environmental conditions to demographic rates and phenotypic traits (body size) via changes in resource availability and individual energetics. We apply the model to the northern Yellowstone elk population and explore population responses to changing patterns of seasonality, incorporating the interdependence of growth, demography, and density-dependent processes operating through population feedback on available resources. We found that small changes in body size distributions can have large impacts on population dynamics but need not cause population responses to environmental change. Environmental changes that altered demographic rates directly, via increasing or decreasing resource availability, led to large population impacts in the absence of substantial changes to body size distributions. In contrast, environmentally driven shifts in body size distributions could occur with little consequence for population dynamics when the effect of environmental change on resource availability was small and seasonally restricted and when strong density-dependent processes counteracted expected population responses. These findings highlight that a robust understanding of how associations between body size and demography influence population responses to environmental change will require knowledge of the shape of the relationship between phenotypic distributions and vital rates, the population status with regard to its carrying capacity, and importantly the nature of the environmentally driven change in body size and carrying capacity.

Conservation value of small reserves.

The importance of large reserves has been long maintained in the scientific literature, often leading to dismissal of the conservation potential of small reserves. However, over half the global protected-area inventory is composed of protected areas that are <100 ha, and the median size of added protected area is decreasing. Studies of the conservation value of small reserves and fragments of natural area are relatively uncommon in the literature. We reviewed SCOPUS and WOK for studies on small reserve and fragment contributions to biodiversity conservation and ecosystem services, and fifty-eight taxon-specific studies were included in the review. Small reserves harbored substantial portions (upward of 50%) of regional species diversity for many taxa (birds, plants, amphibians, and small mammals) and even some endemic, specialist bird species. Unfortunately, small reserves and fragments almost always harbored more generalist and exotic species than large reserves. Community composition depended on habitat quality, surrounding land use (agricultural vs. urban), and reserve and fragment size, which presents opportunities for management and improvement. Small reserves also provided ecosystem services, such as pollination and biological pest control, and cultural services, such as recreation and improved human health. Limitations associated with small reserves, such as extinction debt and support of area-sensitive species, necessitate a complement of larger reserves. However, we argue that small reserves can make viable and significant contributions to conservation goals directly as habitat and indirectly by increasing landscape connectivity and quality to the benefit of large reserves. To effectively conserve biodiversity for future generations in landscapes fragmented by human development, small reserves and fragments must be included in conservation planning.

Valor de Conservación de las Pequeñas Reservas Resumen La importancia de las reservas muy extensas se ha mantenido durante mucho tiempo dentro de la literatura científica, lo que comúnmente lleva a la desestimación del potencial de conservación de las reservas pequeñas. Sin embargo, más de la mitad del inventario mundial de áreas protegidas está compuesto por zonas resguardadas con un tamaño menor a las 100 ha, y el tamaño promedio de área protegida añadida está disminuyendo. Los estudios sobre el valor de conservación de las reservas pequeñas y los fragmentos de área natural son relativamente poco comunes en la literatura. Revisamos estudios sobre las contribuciones de las reservas pequeñas y los fragmentos a la conservación de la biodiversidad y los servicios ambientales en SCOPUS y en WOK. Se incluyeron 58 estudios específicos de taxón en la revisión. Las reservas pequeñas albergaron porciones sustanciales (más del 50%) de diversidad de especies regionales para muchos taxones e incluso algunas especies de aves endémicas y especialistas. Desafortunadamente, las reservas pequeñas y los fragmentos casi siempre albergaron más especies exóticas y generalistas que las reservas grandes. La composición de la comunidad dependió de la calidad del hábitat, el uso de suelo (urbano versus agrícola) adyacente y el tamaño de la reserva o el fragmento, lo que presenta oportunidades de manejo y mejora. Las reservas pequeñas también proporcionaron servicios ambientales, como la polinización y el control biológico de plagas, y servicios culturales, como la recreación y una mejor salud humana. Las limitaciones asociadas con las reservas pequeñas, como la deuda de extinción y el respaldo a especies sensibles al área, requieren de un complemento de reservas más grandes. Sin embargo, argumentamos que las reservas pequeñas pueden tener contribuciones viables y significativas para las metas de conservación directamente como hábitat e indirectamente con el incremento de la conectividad y la calidad de paisajes para el beneficio de las reservas más grandes. Para conservar efectivamente a la biodiversidad para generaciones futuras en paisajes fragmentados por el desarrollo humano, se debe incluir a las reservas pequeñas y a los fragmentos en la planeación de la conservación.

Transmission ecology of canine parvovirus in a multi-host, multi-pathogen system.

Understanding multi-host pathogen maintenance and transmission dynamics is critical for disease control. However, transmission dynamics remain enigmatic largely because they are difficult to observe directly, particularly in wildlife. Here, we investigate the transmission dynamics of canine parvovirus (CPV) using state-space modelling of 20 years of CPV serology data from domestic dogs and African lions in the Serengeti ecosystem. We show that, although vaccination reduces the probability of infection in dogs, and despite indirect enhancement of population seropositivity as a result of vaccine shedding, the vaccination coverage achieved has been insufficient to prevent CPV from becoming widespread. CPV is maintained by the dog population and has become endemic with approximately 3.5-year cycles and prevalence reaching approximately 80%. While the estimated prevalence in lions is lower, peaks of infection consistently follow those in dogs. Dogs exposed to CPV are also more likely to become infected with a second multi-host pathogen, canine distemper virus. However, vaccination can weaken this coupling, raising questions about the value of monovalent versus polyvalent vaccines against these two pathogens. Our findings highlight the need to consider both pathogen- and host-level community interactions when seeking to understand the dynamics of multi-host pathogens and their implications for conservation, disease surveillance and control programmes.

Anthropogenic modifications to fire regimes in the wider Serengeti-Mara ecosystem.

Fire is a key driver in savannah systems and widely used as a land management tool. Intensifying human land uses are leading to rapid changes in the fire regimes, with consequences for ecosystem functioning and composition. We undertake a novel analysis describing spatial patterns in the fire regime of the Serengeti-Mara ecosystem, document multidecadal temporal changes and investigate the factors underlying these patterns. We used MODIS active fire and burned area products from 2001 to 2014 to identify individual fires; summarizing four characteristics for each detected fire: size, ignition date, time since last fire and radiative power. Using satellite imagery, we estimated the rate of change in the density of livestock bomas as a proxy for livestock density. We used these metrics to model drivers of variation in the four fire characteristics, as well as total number of fires and total area burned. Fires in the Serengeti-Mara show high spatial variability-with number of fires and ignition date mirroring mean annual precipitation. The short-term effect of rainfall decreases fire size and intensity but cumulative rainfall over several years leads to increased standing grass biomass and fuel loads, and, therefore, in larger and hotter fires. Our study reveals dramatic changes over time, with a reduction in total number of fires and total area burned, to the point where some areas now experience virtually no fire. We suggest that increasing livestock numbers are driving this decline, presumably by inhibiting fire spread. These temporal patterns are part of a global decline in total area burned, especially in savannahs, and we caution that ecosystem functioning may have been compromised. Land managers and policy formulators need to factor in rapid fire regime modifications to achieve management objectives and maintain the ecological function of savannah ecosystems.

Disentangling serology to elucidate henipa- and filovirus transmission in Madagascar fruit bats.

Bats are reservoirs for emerging human pathogens, including Hendra and Nipah henipaviruses and Ebola and Marburg filoviruses. These viruses demonstrate predictable patterns in seasonality and age structure across multiple systems; previous work suggests that they may circulate in Madagascar's endemic fruit bats, which are widely consumed as human food. We aimed to (a) document the extent of henipa- and filovirus exposure among Malagasy fruit bats, (b) explore seasonality in seroprevalence and serostatus in these bat populations and (c) compare mechanistic hypotheses for possible transmission dynamics underlying these data. To this end, we amassed and analysed a unique dataset documenting longitudinal serological henipa- and filovirus dynamics in three Madagascar fruit bat species. We uncovered serological evidence of exposure to Hendra-/Nipah-related henipaviruses in Eidolon dupreanum, Pteropus rufus and Rousettus madagascariensis, to Cedar-related henipaviruses in E. dupreanum and R. madagascariensis and to Ebola-related filoviruses in P. rufus and R. madagascariensis. We demonstrated significant seasonality in population-level seroprevalence and individual serostatus for multiple viruses across these species, linked to the female reproductive calendar. An age-structured subset of the data highlighted evidence of waning maternal antibodies in neonates, increasing seroprevalence in young and decreasing seroprevalence late in life. Comparison of mechanistic epidemiological models fit to these data offered support for transmission hypotheses permitting waning antibodies but retained immunity in adult-age bats. Our findings suggest that bats may seasonally modulate mechanisms of pathogen control, with consequences for population-level transmission. Additionally, we narrow the field of candidate transmission hypotheses by which bats are presumed to host and transmit potentially zoonotic viruses globally.

Population viability and harvest sustainability for Madagascar lemurs.

Subsistence hunting presents a conservation challenge by which biodiversity preservation must be balanced with safeguarding of human livelihoods. Globally, subsistence hunting threatens primate populations, including Madagascar's endemic lemurs. We used population viability analysis to assess the sustainability of lemur hunting in Makira Natural Park, Madagascar. We identified trends in seasonal hunting of 11 Makira lemur species from household interview data, estimated local lemur densities in populations adjacent to focal villages via transect surveys, and quantified extinction vulnerability for these populations based on species-specific demographic parameters and empirically derived hunting rates. We compared stage-based Lefkovitch with periodic Leslie matrices to evaluate the impact of regional dispersal on persistence trajectories and explored the consequences of perturbations to the timing of peak hunting relative to the lemur birth pulse, under assumptions of density-dependent reproductive compensation. Lemur hunting peaked during the fruit-abundant wet season (March-June). Estimated local lemur densities were roughly inverse to body size across our study area. Life-history modeling indicated that hunting most severely threatened the species with the largest bodies (i.e., Hapalemur occidentalis, Avahi laniger, Daubentonia madagascariensis, and Indri indi), characterized by late-age reproductive onsets and long interbirth intervals. In model simulations, lemur dispersal within a regional metapopulation buffered extinction threats when a majority of local sites supported growth rates above the replacement level but drove regional extirpations when most local sites were overharvested. Hunt simulations were most detrimental when timed to overlap lemur births (a reality for D. madagascariensis and I. indri). In sum, Makira lemurs were overharvested. Regional extirpations, which may contribute to broad-scale extinctions, will be likely if current hunting rates persist. Cessation of anthropogenic lemur harvest is a conservation priority, and development programs are needed to help communities switch from wildlife consumption to domestic protein alternatives.

Population trends for two Malagasy fruit bats.

Madagascar is home to three endemic species of Old World Fruit Bat, which are important pollinators and seed dispersers. We aimed to quantitatively assess population trajectories for the two largest of these species, the IUCN-listed 'Vulnerable' Eidolon dupreanum and Pteropus rufus. To this end, we conducted a longitudinal field study, in which we live-captured E. dupreanum and P. rufus, estimated species-specific fecundity rates, and generated age-frequency data via histological analysis of cementum annuli layering in tooth samples extracted from a subset of individuals. We fit exponential models to resulting data to estimate annual survival probabilities for adult bats (s A = .794 for E. dupreanum; s A = .511 for P. rufus), then applied Lefkovitch modeling techniques to infer the minimum required juvenile survival rate needed to permit longterm population persistence. Given estimated adult survival, population persistence was only possible for E. dupreanum when field-based fecundity estimates were replaced by higher values reported in the literature for related species. For P. rufus, tooth-derived estimates of adult survival were so low that even assumptions of perfect (100%) juvenile annual survival would not permit stable population trajectories. Age-based survival analyses were further supported by longitudinal exit counts carried out from 2013-2018 at three local P. rufus roost sites, which demonstrated a statistically significant, faintly negative time trend, indicative of subtle regional population declines. These results suggest that Malagasy fruit bat species face significant threats to population viability, with P. rufus particularly imperiled. Immediate conservation interventions, including habitat restoration and cessation of legally sanctioned bat hunting, are needed to protect Madagascar's fruit bats into the future.

Complementary Paths to Chagas Disease Elimination: The Impact of Combining Vector Control With Etiological Treatment.

Background: The World Health Organization's 2020 goals for Chagas disease are (1) interrupting vector-borne intradomiciliary transmission and (2) having all infected people under care in endemic countries. Insecticide spraying has proved efficacious for reaching the first goal, but active transmission remains in several regions. For the second, treatment has mostly been restricted to recently infected patients, who comprise only a small proportion of all infected individuals. Methods: We extended our previous dynamic transmission model to simulate a domestic Chagas disease transmission cycle and examined the effects of both vector control and etiological treatment on achieving the operational criterion proposed by the Pan American Health Organization for intradomiciliary, vectorial transmission interruption (ie, <2% seroprevalence in children <5 years of age). Results: Depending on endemicity, an antivectorial intervention that decreases vector density by 90% annually would achieve the transmission interruption criterion in 2-3 years (low endemicity) to >30 years (high endemicity). When this strategy is combined with annual etiological treatment in 10% of the infected human population, the seroprevalence criterion would be achieved, respectively, in 1 and 11 years. Conclusions: Combining highly effective vector control with etiological (trypanocidal) treatment in humans would substantially reduce time to transmission interruption as well as infection incidence and prevalence. However, the success of vector control may depend on prevailing vector species. It will be crucial to improve the coverage of screening programs, the performance of diagnostic tests, the proportion of people treated, and the efficacy of trypanocidal drugs. While screening and access can be incremented as part of strengthening the health systems response, improving diagnostics performance and drug efficacy will require further research.

Pathogen spillover during land conversion.

Pathogen spillover from wildlife to domestic animals and humans, and the reverse, has caused significant epidemics and pandemics worldwide. Although pathogen emergence has been linked to anthropogenic land conversion, a general framework to disentangle underlying processes is lacking. We develop a multi-host model for pathogen transmission between species inhabiting intact and converted habitat. Interspecies contacts and host populations vary with the proportion of land converted; enabling us to quantify infection risk across a changing landscape. In a range of scenarios, the highest spillover risk occurs at intermediate levels of habitat loss, whereas the largest, but rarest, epidemics occur at extremes of land conversion. This framework provides insights into the mechanisms driving disease emergence and spillover during land conversion. The finding that the risk of spillover is highest at intermediate levels of habitat loss provides important guidance for conservation and public health policy.

Pyrodiversity interacts with rainfall to increase bird and mammal richness in African savannas.

Fire is a fundamental process in savannas and is widely used for management. Pyrodiversity, variation in local fire characteristics, has been proposed as a driver of biodiversity although empirical evidence is equivocal. Using a new measure of pyrodiversity (Hempson et al.), we undertook the first continent-wide assessment of how pyrodiversity affects biodiversity in protected areas across African savannas. The influence of pyrodiversity on bird and mammal species richness varied with rainfall: strongest support for a positive effect occurred in wet savannas (> 650 mm/year), where species richness increased by 27% for mammals and 40% for birds in the most pyrodiverse regions. Range-restricted birds were most increased by pyrodiversity, suggesting the diversity of fire regimes increases the availability of rare niches. Our findings are significant because they explain the conflicting results found in previous studies of savannas. We argue that managing savanna landscapes to increase pyrodiversity is especially important in wet savannas.

Toward an integrative molecular approach to wildlife disease.

Pathogens pose serious threats to human health, agricultural investment, and biodiversity conservation through the emergence of zoonoses, spillover to domestic livestock, and epizootic outbreaks. As such, wildlife managers are often tasked with mitigating the negative effects of disease. Yet, parasites form a major component of biodiversity that often persist. This is due to logistical challenges of implementing management strategies and to insufficient understanding of host-parasite dynamics. We advocate for an inclusive understanding of molecular diversity in driving parasite infection and variable host disease states in wildlife systems. More specifically, we examine the roles of genetic, epigenetic, and commensal microbial variation in disease pathogenesis. These include mechanisms underlying parasite virulence and host resistance and tolerance, and the development, regulation, and parasite subversion of immune pathways, among other processes. Case studies of devil facial tumor disease in Tasmanian devils (Sarcophilus harrisii) and chytridiomycosis in globally distributed amphibians exemplify the broad range of questions that can be addressed by examining different facets of molecular diversity. For particularly complex systems, integrative molecular analyses present a promising frontier that can provide critical insights necessary to elucidate disease dynamics operating across scales. These insights enable more accurate risk assessment, reconstruction of transmission pathways, discernment of optimal intervention strategies, and development of more effective and ecologically sound treatments that minimize damage to the host population and environment. Such measures are crucial when mitigating threats posed by wildlife disease to humans, domestic animals, and species of conservation concern.

Synergistic and antagonistic interactions between bednets and vaccines in the control of malaria.

It is extremely likely that the malaria vaccines currently in development will be used in conjunction with treated bednets and other forms of malaria control. The interaction of different intervention methods is at present poorly understood in a disease such as malaria where immunity is more complex than for other pathogens that have been successfully controlled by vaccination. Here we develop a general mathematical model of malaria transmission to examine the interaction between vaccination and bednets. Counterintuitively, we find that the frailty of malaria immunity will potentially cause both synergistic and antagonistic interactions between vaccination and the use of bednets. We explore the conditions that create these tensions, and outline strategies that minimize their detrimental impact. Our analysis specifically considers the three leading vaccine classes currently in development: preerythrocytic (PEV), blood stage (BSV), and transmission blocking (TBV). We find that the combination of BSV with treated bednets can lead to increased morbidity with no added value in terms of elimination; the interaction is clearly antagonistic. In contrast, there is strong synergy between PEV and treated bednets that may facilitate elimination, although transient stages are likely to increase morbidity. The combination of TBV with treated bednets is synergistic, lowering both morbidity and elimination thresholds. Our results suggest that vaccines will not provide a straightforward solution to malaria control, and that future programs need to consider the synergistic and antagonistic interactions between vaccines and treated bednets.

Dynamics of a morbillivirus at the domestic-wildlife interface: Canine distemper virus in domestic dogs and lions.

Morbilliviruses cause many diseases of medical and veterinary importance, and although some (e.g., measles and rinderpest) have been controlled successfully, others, such as canine distemper virus (CDV), are a growing concern. A propensity for host-switching has resulted in CDV emergence in new species, including endangered wildlife, posing challenges for controlling disease in multispecies communities. CDV is typically associated with domestic dogs, but little is known about its maintenance and transmission in species-rich areas or about the potential role of domestic dog vaccination as a means of reducing disease threats to wildlife. We address these questions by analyzing a long-term serological dataset of CDV in lions and domestic dogs from Tanzania's Serengeti ecosystem. Using a Bayesian state-space model, we show that dynamics of CDV have changed considerably over the past three decades. Initially, peaks of CDV infection in dogs preceded those in lions, suggesting that spill-over from dogs was the main driver of infection in wildlife. However, despite dog-to-lion transmission dominating cross-species transmission models, infection peaks in lions became more frequent and asynchronous from those in dogs, suggesting that other wildlife species may play a role in a potentially complex maintenance community. Widespread mass vaccination of domestic dogs reduced the probability of infection in dogs and the size of outbreaks but did not prevent transmission to or peaks of infection in lions. This study demonstrates the complexity of CDV dynamics in natural ecosystems and the value of long-term, large-scale datasets for investigating transmission patterns and evaluating disease control strategies.