The ecology of emerging infectious disease From the New York Times, July 16, 2012

Eastern equine encephalitis kills 4 people in Florida: Aug 18, 2010

CDC: West Nile outbreak largest ever seen in U.S. Posted on: 5:39 pm, August 26, 2012, by Alix Bryan Update to CDC's Sexually Transmitted Diseases Treatment Guidelines, 2010: Oral Cephalosporins No Longer a Recommended Treatment for Gonococcal Infections Weekly August 10, 2012 / 61(31); Uganda Ebola outbreak confirmed Health officials say mysterious illness that has killed 14 people in western Ugandan district of Kibaale is Ebola virus (July 29, 2012)

Infectious disease is a current important threat to human health and well being and to the integrity of natural and managed ecosystems World Health Organization (1990) 37% human mortality attributable to infectious disease 1.7 billion tuberculosis infections 267 million cases of malaria 50 million reported cases of dengue fever Institute of Medicine (1992) 54 new infectious diseases in US since1940 Nature 2008 (Jones et al.) 300 new human pathogens world-wide from 1940 – 2003

What is an emerging infectious disease (EID)? One that has recently increased in occurrence One that has recently expanded its geographic range One that is caused by novel pathogen Includes the emergence of novel pathogens and reemergence of previously controlled infectious diseases

Examples of emerging infectious diseases Increased incidence - Lyme disease Increased impact - Tuberculosis Increased geographic range - West Nile virus Evolution of new strain - Influenza viruses (H1N1) Pathogen entering humans - Nipah virus Newly discovered pathogen - Hendra virus Previously controlled but now re-emerging: Dengue fever

The rate of emergence is increasing Emerging infectious diseases (EID) recent increase in occurrence recent increase in geographic range, or effect caused by a novel pathogen

What factors do you think account for emergence of new diseases and re- emergence of old ones?

Drivers of emerging human pathogens* Changes in land use and agricultural practices Changes in human demography Poor population health Hospital and medical procedures Pathogen evolution Contamination of food or water supplies International travel Failure of public health programs International trade Climate change *In order from most to least number of pathogens affected (2005)

the study of the distribution and abundance of organisms Ecology What does ecology have to do with infectious disease?

Predation and parasitism Infectious disease constitutes a classic form of species interaction (predator-prey) studied by ecologists. Competition FacilitationMutualism Predation

CONSUMER - RESOURCE INTERACTIONS LethalityIntimacy HILOW HI Host - ParasitoidPredator-prey LOW Host - ParasiteGrazers

Two examples of how tools and concepts from ecology can be used to help predict, prevent and control outbreaks and emergence of infectious disease 1.Use of a mathematical model of species interactions to evaluate alternate means of responding to outbreak of the novel disease SARS. 2.The role of ecology in predicting the occurrence of Lyme Disease

What is a model and what can you do with it?

y = mx + b A model is a simplified representation of something Models can be used to describe, explain, or understand more complex reality. Physical models Conceptual model Mathematical model

Some questions that might be answered with a mathematical model of an infectious disease 1.What are the conditions under which an epidemic will occur? 2.What fraction of the population will become infected? 3.How would vaccination change the speed or duration of an epidemic? 4.How will treatment or other intervention affect the course of an epidemic?

SIR #susceptible #infected#removed Ecologists use SIR models to study the interactions between parasites and their hosts N is the total number of individuals in the population of hosts S is the number that are susceptible to a disease I is the number of individuals that are infected with the disease R is the number that are not susceptible or infected (removed) S + I + R = N

S IR  is the rate at which the disease is transmitted #susceptible #infected#removed   is the rate of recovery from the disease S + I + R = N Ecologists use SIR models to study the interactions between parasites and their hosts

S IR #susceptible#infected#removed  Equations describe how the numbers in each box change over time. The change in the number of susceptible individuals through time The change in the number of infected individuals through time The change in the number of removed individuals through time

S IR  is the rate at which the disease is transmitted  is the rate of recovery from the disease What information is in the sign of dI/dt? #susceptible #infected#removed 

Some questions that might be answered with a mathematical model of an infectious disease 1.What are the conditions under which an epidemic will occur? 2.What fraction of the population will become infected? 3.How would vaccination change the speed or duration of an epidemic? 4.How will treatment or other intervention affect the course of an epidemic?

SARS; Severe acute respiratory syndrome. Reservoir host

Will there be a pandemic?

Possible responses to an emerging novel viral epidemic? Vaccination Isolation of infected individuals Quarantine of contacts Culling (of the reservoir, not the victims) How do we decide which responses will be most effective? Mathematical models are used to explain, explore and predict how biological systems work. We can conduct “experiments” with models that would be impossible or too slow to be used in an on-going epidemic.

Lipsitch et al used a mathematical model to predict the effects of different control measures on the initial outbreak of SARS

Schematic diagram of a model of SARS Indicates effect of intervention Latent Infection designates individuals who are infected but do not have active disease and so are not (yet) infectious

The ModelThe ODE

Schematic diagram of a model of SARS Use computer simulation to ask how isolation and/or quarantine would affect the course of an epidemic Indicates effects of intervention S I R Latent Infection designates individuals who are infected but do not have active disease and so are not (yet) infectious

SARS Epilogue Over 8000 cases world wide, over 750 deaths Average mortality rate 9.6%, but variable among age groups Cases reported from >2 dozen countries on 4 continents. Last reported case in 2004 (lab acquired infection) Development of vaccine is on-going Early intervention is critical, greater surveillance is needed for prediction and early detection

Agent of Lyme disease Yersinea pestis agent of plague About 40% of all human diseases are caused by bacteria. Most cause disease via the production of toxins. Exotoxins are secreted or induced by live bacteria. Endotoxins are released when bacteria die.

Lyme disease From CDC report 2006

How many humans view Lyme disease Borrelia burgdorferiIxodes scapularis Host infection

How an ecologist sees the system in which Lyme disease is embedded vector reservoir

Tick vector life cycle and host associations uninfected infected?

How an ecologist sees the system in which Lyme disease is embedded vector reservoir

Predicting risk of exposure from ecological data Possible predictors deerweatherreservoirsweathermammals acorns Affect populations of rodents and attract deer Affect survival of larval and nymphal ticks off hosts Reservoir and “taxi” Reservoir

The variables most closely associated with Lyme disease incidence Chipmunk density a year earlierAcorn abundance 2 years earlier

What determines spatial variation in risk of infection? Abundance of reservoir hosts, vectors, and humans must coincide, but the mechanisms underlying the distribution of each may vary. “Hot spots” on North Atlantic coast, upper midwest, and northern California

How spatial variation in biodiversity of potential reservoir species influence the risk of Lyme disease Logic: As the most competent reservoir host becomes a smaller fraction of the community, fewer tick nymphs will be infectious and the number of cases of Lyme disease will decline. This is called a dilution effect. Ostfeld and Keesing 2000 Measured biodiversity of different components of the reservoir community in 10 “states” along the US eastern seaboard and looked for a relationship to cases of Lyme disease.

Effects of biodiversity on the incidence of Lyme disease Suggests many birds may be competent reservoirs Consistent with a dilution effect by less competent reservoirs Consistent with known ability of fence lizards to clear the bacteria Keesing and Ostfeld 2000 Conservation Biology r 2 = 0.54 r 2 = 0.46 r 2 = 0.47

Some contributions from ecological analyses of Lyme disease Nymphs cause more infections than adults The abundance of chipmunks and acorns are better predictors of the risk of Lyme disease than weather or deer abundance Greater biodiversity of the small mammal community reduces the risk of Lyme disease

It’s not just Humans Domestic animals: FMD in GB, Brucellosis in YNP Wildlife: Chytrid fungus, white band disease

It’s not just animals Dutch elm disease Sudden oak death Targets of agricultural biowarfare

Who should take responsibility for prevention of disease emergence and spread?

Roles in prediction, prevention, and control of infectious disease Medicine: diagnosis and treatment of individuals Biomedical research: identification of pathogens, development of treatment and defense of individuals Epidemiology: Analysis of patterns of disease occurrence and their relationship to potential causes Ecology: incorporate biological mechanism into prediction, prevention, and control of disease at the population, species, community, and ecosystem levels Public health: Devising and implementing policy and practice to reduce the occurrence and spread of disease Education:?

The study of infectious disease is inherently multidisciplinary but has fallen through the cracks, and is not taught systematically Microbiology Immunology Public Health Ecology Mathematics

Summary 1.The emergence and reemergence of infectious disease is a serious threat. 2.Humans are not separate from the environment. Our actions and behaviors have consequences for the structure and integrity of natural ecosystems. 3.Understanding ecology provides one set of tools to address the problem of infectious disease 4.Current popular visibility provides an opportunity to educate students