Barbara A. Han

• Ph.D
• Disease Ecologist at Cary Institute of Ecosystem Studies

As the frequency and prevalence of zoonotic diseases increase worldwide, investigating how mammal host distributions determine patterns of human disease and predicting which regions are at greatest risk for future zoonotic disease emergence are two goals which both require better understanding of the current distributions of zoonotic hosts and path...

Emerging infectious diseases are among the most destructive and costly natural forces [1]: In terms of human and monetary losses, epidemics and pandemics rank with other major natural disasters, such as earthquakes or tsunamis. And like earthquakes and tsunamis, much of the destructive potential of infectious diseases stems from the fact that they...

Significance Forecasting reservoirs of zoonotic disease is a pressing public health priority. We apply machine learning to datasets describing the biological, ecological, and life history traits of rodents, which collectively carry a disproportionate number of zoonotic pathogens. We identify particular rodent species predicted to be novel zoonotic...

Animal migrations are often spectacular, and migratory species harbor zoonotic pathogens of importance to humans. Animal migrations are expected to enhance the global spread of pathogens and facilitate cross-species transmission. This does happen, but new research has also shown that migration allows hosts to escape from infected habitats, reduces...

Motivation Ecological systems are complex. Representing heterogeneous knowledge about ecological systems is a pervasive challenge because data are generated from many subdisciplines, exist in disparate sources, and only capture a subset of interactions underpinning system dynamics. Knowledge graphs (KGs) have been successfully applied to organize h...

Understanding where and when pathogens occur in the environment has implications for reservoir population health and infection risk. In reservoir hosts, infection status and pathogen shedding are affected by processes interacting across different scales: from landscape features affecting host location and transmission to within-host processes affec...

The emergence of mosquito-borne zoonoses has continually increased over the past decade, posing a significant global public health challenge. Ecological theory can point to the characteristics of populations that make them more likely to form reservoirs of disease. The pace of life hypothesis posits that species with more rapid reproduction and sho...

Ecological systems are complex. Representing heterogeneous knowledge about ecological systems is a pervasive challenge because data are generated from many subdisciplines, exist in disparate sources, and only capture a subset of important interactions underpinning system structure, resilience, and dynamics. Knowledge graphs have been successfully a...

Emerging infectious diseases are increasingly understood as a hallmark of the Anthropocene 1–3 . Most experts agree that anthropogenic ecosystem change and high-risk contact among people, livestock, and wildlife have contributed to the recent emergence of new zoonotic, vector-borne, and environmentally-transmitted pathogens 1,4–6 . However, the ext...

Ebolaviruses have the ability to infect a wide variety of species, with many African mammals potentially serving either as primary reservoirs or secondary amplifying hosts. Previous work has shown that frugivorous bats and primates are often associated with spillover and outbreaks. Yet the role that patterns of biodiversity, either of mammalian hos...

Despite repeated spillover transmission and their potential to cause significant morbidity and mortality in human hosts, the New World mammarenaviruses remain largely understudied. These viruses are endemic to South America, with animal reservoir hosts covering large geographic areas and whose transmission ecology and spillover potential are driven...

Global climate change is predicted to cause range shifts in the mosquito species that transmit pathogens to humans and wildlife. Recent modeling studies have sought to improve our understanding of the relationship between temperature and the transmission potential of mosquito‐borne pathogens. However, the role of the vertebrate host population, inc...

Mayaro virus (MAYV) is a mosquito-borne Alphavirus that is widespread in South America. MAYV infection often presents with non-specific febrile symptoms but may progress to debilitating chronic arthritis or arthralgia. Despite the pandemic threat of MAYV, its true distribution remains unknown. The objective of this study was to clarify the geograph...

Food availability determines where animals use space across a landscape and therefore affects the risk of encounters that lead to zoonotic spillover. This relationship is evident in Australian flying foxes (Pteropus spp; fruit bats), where acute food shortages precede clusters of Hendra virus spillovers. Using explainable artificial intelligence, w...

Mayaro Virus (MAYV) is an emerging health threat in the Americas that can cause febrile illness as well as debilitating arthralgia or arthritis. To better understand the geographic distribution of MAYV risk, we developed a georeferenced database of MAYV occurrence based on peer-reviewed literature and unpublished reports. Here we present this compe...

The spatio-temporal distribution of leishmaniasis, a parasitic vector-borne zoonotic disease, is significantly impacted by land-use change and climate warming in the Americas. However, predicting and containing outbreaks is challenging as the zoonotic Leishmania system is highly complex: leishmaniasis (visceral, cutaneous and muco-cutaneous) in hum...

Pathogens can spill over and infect new host species by overcoming a series of ecological and biological barriers. Hendra virus (HeV) circulates in Australian flying foxes and provides a data‐rich study system for identifying environmental drivers underlying spillover events. The frequency of spillover events to horses has varied interannually sinc...

Background Mayaro virus (MAYV) is a mosquito-borne Alphavirus that is widespread in South America. MAYV infection often presents with non-specific febrile symptoms but may progress to debilitating chronic arthritis or arthralgia. Despite the pandemic threat of MAYV, its true distribution remains unknown. The objective of this study was to clarify t...

Mayaro Virus (MAYV) is an emerging health threat in the Americas that can cause febrile illness as well as debilitating arthralgia or arthritis. To better understand the geographic distribution of MAYV risk, we developed a georeferenced database of MAYV occurrence based on peer-reviewed literature and unpublished reports. Here we present this compe...

[This corrects the article DOI: 10.1371/journal.pntd.0007393.].

We explore how animal host traits, phylogenetic identity and cell receptor sequences relate to infection status and mortality from ebolaviruses. We gathered exhaustive databases of mortality from Ebolavirus after exposure and infection status based on PCR and antibody tests. We performed ridge regressions predicting mortality and infection as a fun...

Population fluctuations are widespread across the animal kingdom, especially in the order Rodentia, which includes many globally important reservoir species for zoonotic pathogens. The implications of these fluctuations for zoonotic spillover remain poorly understood. Here, we report a global empirical analysis of data describing the linkages betwe...

Spatio-temporal distribution of leishmaniasis, a parasitic vector-borne zoonotic disease, is significantly impacted by land-use change and climate warming in the Americas. However, predicting and containing outbreaks is challenging as the zoonotic Leishmania system is highly complex: Leishmaniasis (visceral, cutaneous and muco-cutaneous) in human...

Aim Amphibian populations are threatened globally by anthropogenic change and Batrachochytrium dendrobatidis (Bd), a fungal pathogen causing chytridiomycosis disease to varying degrees of severity. A closely related new fungal pathogen, Batrachochytrium salamandrivorans (Bsal), has recently left its supposed native range in Asia and decimated some...

Increasing incidence of tick-borne human diseases and geographic range expansion of tick vectors elevates the importance of research on characteristics of tick species that transmit pathogens. Despite their global distribution and role as vectors of pathogens such as Rickettsia spp., ticks in the genus Dermacentor Koch, 1844 (Acari: Ixodidae) have...

The incidence of vector-borne diseases is rising as deforestation, climate change, and globalization bring humans in contact with arthropods that can transmit pathogens. In particular, incidence of American Cutaneous Leishmaniasis (ACL), a parasitic disease transmitted by sandflies, is increasing as previously intact habitats are cleared for agricu...

El orden Carnivora incluye más de 300 especies que varían en tamaño en muchos órdenes de magnitud y habitan en todos los biomas principales, desde las selvas tropicales hasta los mares polares. La gran diversidad de parásitos carnívoros representa una fuente de posibles enfermedades emergentes en humanos. El riesgo zoonótico de este grupo puede deb...

Despite the global investment in One Health disease surveillance, it remains difficult and costly to identify and monitor the wildlife reservoirs of novel zoonotic viruses. Statistical models can guide sampling target prioritisation, but the predictions from any given model might be highly uncertain; moreover, systematic model validation is rare, a...

Improving our understanding of Mayaro virus (MAYV) ecology is critical to guide surveillance and risk assessment. We conducted a PRISMA-adherent systematic review of the published and grey literature to identify potential arthropod vectors and non-human animal reservoirs of MAYV. We searched PubMed/MEDLINE, Embase, Web of Science, SciELO and grey-l...

Back and forth transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between humans and animals will establish wild reservoirs of virus that endanger long-term efforts to control COVID-19 in people and to protect vulnerable animal populations. Better targeting surveillance and laboratory experiments to validate zoonotic poten...

Species diversity may play an important role in the modulation of pathogen transmission through the dilution effect. Infectious disease models can help elucidate mechanisms that may underlie this effect. While many modeling studies have assumed direct host-to-host transmission, many pathogens are transmitted through the environment. We present a ma...

In the light of the urgency raised by the COVID-19 pandemic, global investment in wildlife virology is likely to increase, and new surveillance programmes will identify hundreds of novel viruses that might someday pose a threat to humans. To support the extensive task of laboratory characterization, scientists may increasingly rely on data-driven r...

Helminths are parasites that cause disease at considerable cost to public health and present a risk for emergence as novel human infections. Although recent research has elucidated characteristics conferring a propensity to emergence in other parasite groups (e.g. viruses), the understanding of factors associated with zoonotic potential in helminth...

The order Carnivora includes over 300 species that vary many orders of magnitude in size and inhabit all major biomes, from tropical rainforests to polar seas. The high diversity of carnivore parasites represents a source of potential emerging diseases of humans. Zoonotic risk from this group may be driven in part by exceptionally high functional d...

Current methods for viral discovery target evolutionarily conserved proteins that accurately identify virus families but remain unable to distinguish the zoonotic potential of newly discovered viruses. Here, we apply an attention-enhanced long-short-term memory (LSTM) deep neural net classifier to a highly conserved viral protein target to predict...

Improving our understanding of Mayaro virus (MAYV) ecology is critical to guide surveillance and risk assessment. We conducted a PRISMA-adherent systematic review of the published and grey literature to identify potential arthropod vectors and non-human animal reservoirs of MAYV. We searched PubMed, Embase, Web of Science, SciELO and grey-literatur...

In light of the urgency raised by the COVID-19 pandemic, global investment in wildlife virology is likely to increase, and new surveillance programs will identify hundreds of novel viruses that might someday pose a threat to humans. Our capacity to identify which viruses are capable of zoonotic emergence depends on the existence of a technology—a m...

Helminths are parasites that cause disease at considerable cost to public health and present a risk for emergence as novel human infections. Although recent research has elucidated characteristics conferring a propensity to emergence in other parasite groups (e.g. viruses), the understanding of factors associated with zoonotic potential in helminth...

Spillback transmission from humans to animals, and secondary spillover from animal hosts back into humans, have now been documented for SARS-CoV-2. In addition to threatening animal health, virus variants arising from novel animal hosts have the potential to undermine global COVID-19 mitigation efforts. Numerous studies have therefore investigated...

SARS-CoV-1 and SARS-CoV-2 are not phylogenetically closely related; however, both use the ACE2 receptor in humans for cell entry. This is not a universal sarbecovirus trait; for example, many known sarbecoviruses related to SARS-CoV-1 have two deletions in the receptor binding domain of the spike protein that render them incapable of using human AC...

Aim Prediction of novel reservoirs of zoonotic pathogens would be improved by the identification of interspecific drivers of host competence (i.e., the ability to transmit pathogens to new hosts or vectors). Tick‐borne pathogens can provide a useful model system, because larvae become infected only when feeding on a competent host during their firs...

Yellow fever virus (YFV) is the etiological agent of yellow fever (YF), an acute hemorrhagic vector-borne disease with a significant impact on public health, is endemic across tropical regions in Africa and South America. The virus is maintained in two ecologically and evolutionary distinct transmission cycles: an enzootic, sylvatic cycle, where th...

SARS-CoV-1 and SARS-CoV-2 are not phylogenetically closely related; however, both use the ACE2 receptor in humans for cell entry. This is not a universal sarbecovirus trait; for example, many known sarbecoviruses related to SARS-CoV-1 have two deletions in the receptor binding domain of the spike protein that render them incapable of using human AC...

Despite massive investment in research on reservoirs of emerging pathogens, it remains difficult to rapidly identify the wildlife origins of novel zoonotic viruses. Viral surveillance is costly but rarely optimized using model-guided prioritization strategies, and predictions from a single model may be highly uncertain. Here, we generate an ensembl...

Our understanding of ecological processes is built on patterns inferred from data. Applying modern analytical tools such as machine learning to increasingly high dimensional data offers the potential to expand our perspectives on these processes, shedding new light on complex ecological phenomena such as pathogen transmission in wild populations. H...

Pathogens and parasites (henceforth “pathogens”) can make up a large percentage of the biomass found in ecosystems, and therefore, their impacts on ecosystem processes should be prominent. Pathogens influence ecosystem processes by affecting the abundance or phenotype of hosts and through direct contributions to ecosystem production. However, there...

Aim Predicting novel reservoirs of zoonotic pathogens would be improved by identifying inter-specific drivers of host competence, the ability to transmit pathogens to new hosts or vectors. Tick-borne pathogens can provide a useful model system, as larvae become infected only when feeding on a competent host during their first bloodmeal. For tick-bo...

In this issue of the Paper Trail, an arising and established researcher connect on the topic of host–pathogen associations in disease ecology and predicting their occurrence using machine learning. The former, a postdoctoral scholar at UC Davis, has set his sights on developing tools for surveillance of emerging viruses that pose pandemic threats,...

Much of the basic ecology of Ebolavirus remains unresolved despite accumulating disease outbreaks, viral strains and evidence of animal hosts. Because human Ebolavirus epidemics have been linked to contact with wild mammals other than bats, traits shared by species that have been infected by Ebolavirus and their phylogenetic distribution could sugg...

The 2018 outbreak of Nipah virus in Kerala, India, highlights the need for global surveillance of henipaviruses in bats, which are the reservoir hosts for this and other viruses. Nipah virus, an emerging paramyxovirus in the genus Henipavirus, causes severe disease and stuttering chains of transmission in humans and is considered a potential pandem...

Disease ecology is a rapidly growing subdiscipline, and mammals and their parasites feature prominently in both historical and more recent research efforts. Nevertheless, the diversity of topics explored, and those not well explored, has not been systematically assessed. We conducted a systematic review of the published scientific literature in dis...

Understanding factors that facilitate interspecific pathogen transmission is a central issue for conservation, agriculture, and human health. Past work showed that host phylogenetic relatedness and geographical proximity can increase cross‐species transmission, but further work is needed to examine the importance of host traits, and species interac...

The global burden of infectious diseases and the increased attention to natural, accidental, and deliberate biological threats has resulted in significant investment in infectious disease research. Translating the results of these studies to inform prevention, detection, and response efforts often can be challenging, especially if prior relationshi...

Body size influences many traits including those that affect host competence, the propensity to cause new infections. Here, we employ a new framework to reveal that, for at least two infections, West Nile virus and Lyme disease, large hosts should be more competent than small ones, but their lower abundance could mitigate their impacts on local ris...

The recent Zika virus (ZIKV) epidemic in the Americas ranks among the largest outbreaks in modern times. Like other mosquito-borne flaviviruses, ZIKV circulates in sylvatic cycles among primates that can serve as reservoirs of spillover infection to humans. Identifying sylvatic reservoirs is critical to mitigating spillover risk, but relevant surve...

Effective public health research and preparedness requires an accurate understanding of which virus species possess or are at risk of developing human transmissibility. Unfortunately, our ability to identify these viruses is limited by gaps in disease surveillance and an incomplete understanding of the process of viral adaptation. By fitting booste...

Descriptions of the predictor variables included in our models. (XLSX)

Variable partial dependence plots, supplementary models with study effort. Partial dependence plots show how the model-predicted probability that a virus is able to spread between humans is affected by individual viral traits when the effects all other predictors are controlled for. These models include the log10-transformed number of PubMed citati...

A ranking of virus species by their mean predicted response probability in the primary GBM model ensemble. Viruses for which there is evidence of human-to-human transmission are given a value of 1 in the column Actual.Response, while viruses which are no known to be transmissible have a value of 0. (CSV)

Family characteristics of false-negative virus species. Each point represents a virus family that contains one or more species known to infect humans. Points represent the families of viruses included in our dataset (those known to infect humans). Red points are the 5 virus families containing the ten known-transmissible species with the lowest mod...

Information on the parameters, AUC scores, and variable relative influence scores of the primary and secondary models. (XLSX)

Variable partial dependence plots, supplementary models with a modified response definition. Partial dependence plots show how the model-predicted probability that a virus is able to spread between humans is affected by individual viral traits when the effects all other predictors are controlled for. In these models, we modified our definition of t...

In the face of mosquito-borne disease outbreaks, effective mosquito control is a primary goal for public health. Insect repellents, containing active compounds such as DEET and picaridin, are a first defence against biting insects. Owing to widespread use and incomplete sewage treatment, these compounds are frequently detected in surface waters, bu...

Aim To explore spatial patterns of helminth parasite diversity, and to investigate three main macroecological patterns – (a) latitude–diversity relationships, (b) positive scaling between parasite and host diversity, and (c) species–area relationships – using a largely underutilized global database of helminth parasite occurrence records. Location...

Numerous factors are contributing to the loss of biodiversity. These include complex effects of multiple abiotic and biotic stressors that may drive population losses. These losses are especially illustrated by amphibians, whose populations are declining worldwide. The causes of amphibian population declines are multifaceted and context-dependent....

The community of host species that a parasite infects is often explained by functional traits and phylogeny, predicting that closely related hosts or those with particular traits share more parasites with other hosts. Previous research has examined parasite community similarity by regressing pairwise parasite community dissimilarity between two hos...

Contact networks are convenient models to investigate epidemics, with nodes and links representing potential hosts and infection pathways, respectively. The outcomes of outbreak simulations on networks are driven both by the underlying epidemic model, and by the networks' structural properties, so that the same pathogen can generate different epide...

Background: With the resurgence of tick-borne diseases such as Lyme disease and the emergence of new tick-borne pathogens such as Powassan virus, understanding what distinguishes vectors from non-vectors, and predicting undiscovered tick vectors is a crucial step towards mitigating disease risk in humans. We aimed to identify intrinsic traits that...

Because the natural reservoir of Ebola virus remains unclear and disease outbreaks in humans have occurred only sporadically over a large region, forecasting when and where Ebola spillovers are most likely to occur constitutes a continuing and urgent public health challenge. We developed a statistical modeling approach that associates 37 human or g...

Illuminating the ecological and evolutionary dynamics of parasites is one of the most pressing issues facing modern science, and is critical for basic science, the global economy and human health. Extremely important to this effort are data on the disease-causing organisms of wild animal hosts (including viruses, bacteria, protozoa, helminths, arth...

Ecosystem scientists will increasingly be called on to inform forecasts and define uncertainty about how changing planet conditions affect human well-being. We should be prepared to leverage the best tools available, including big data. Use of the term ‘big data’ implies an approach that includes capacity to aggregate, search, cross-reference, and...

Because the natural reservoir of Ebola virus remains unclear and disease outbreaks in humans have occurred only spo- radically over a large region, forecasting when and where Ebola spillovers are most likely to occur constitutes a con- tinuing and urgent public health challenge. We developed a statistical modeling approach that associates 37 human...

Detailed methods for the determination of unique Ebola spillover events, selection of data sources and processing of geographic layers, and statistical modeling used in analyses of spatiotemporal fluctuations and triggers of Ebola virus disease spillover, Africa, 1983–2014.

Dates, locations, and sources for the unique set of spillover events used in analyses of spatiotemporal fluctuations and triggers of Ebola virus disease spillover, Africa, 1961–2014.

R code used in analyses of spatiotemporal fluctuations and triggers of Ebola virus disease spillover, Africa, 1983–2014.

Zika is an emerging virus whose rapid spread is of great public health concern. Knowledge about transmission remains incomplete, especially concerning potential transmission in geographic areas in which it has not yet been introduced. To identify unknown vectors of Zika, we developed a data-driven model linking vector species and the Zika virus via...

The technique of Formal Concept Analysis is applied to a dataset describing the traits of rodents, with the goal of identifying zoonotic disease carriers,or those species carrying infections that can spillover to cause human disease. The concepts identified among these species together provide rules-of-thumb about the intrinsic biological features...

Figures and figure supplements

Ebola and other filoviruses pose significant public health and conservation threats by causing high mortality in primates, including humans. Preventing future outbreaks of ebolavirus depends on identifying wildlife reservoirs, but extraordinarily high biodiversity of potential hosts in temporally dynamic environments of equatorial Africa contribute...

A table containing all published records of bat individuals reported to the species level that have been sampled for filoviruses using a variety of diagnostic methods. From the primary literature (Reference), we report the total number of bats tested via PCR (PCR tested), antibody tests (Ab tested), and the number of virus isolation attempts (iso a...

A list of the coverage and the definitions for all variables included in the boosted regression tree (excluding taxonomic families). Coverage is calculated as a percentage of the total bat species (out of N = 1116) and a percentage of the total filovirus-positive bat species (out of N = 21) for which there were data available for a given variable....

Spearman’s rank correlation analyses of bat species rankings produced by boosted regression models on complete data compared to data missing 1%-20% of randomly selected traits (covariates). (PDF)

Species predictions generated by the generalized boosted regression model. The first 112 species comprise the 90th percentile probability of novel filovirus-positive bat species. Label is a binomial variable denoting filovirus-positivity. Probability is a transformation of model outputs. (PDF)

Range maps of predicted additional filovirus-positive bat species in the 90th, 95th, and 99th percentile probability. (PNG)

Tuning parameters (shrinkage, interaction depth), performance metrics (AUC), and complete trait profiles produced by generalized boosted regression models examining filovirus-positive status as a binary variable (Bernoulli error distribution). The final model includes the number of citations per bat species in Web of Science (WOS_HITS), showing tha...

As the outbreak of Ebola virus disease (EVD) in West Africa is now contained, attention is turning from control to future outbreak prediction and prevention. Building on a previously published zoonotic niche map (Pigott et al., 2014), this study incorporates new human and animal occurrence data and expands upon the way in which potential bat EVD re...