Disease Ecology Today we will discuss: History and Overview of Emerging Infectious Diseases How are human exposures to disease affected by ecosystem attributes? Lyme disease How does climate change influence the prevalence and severity of certain diseases? Cholera Evolution of pathogens to antibiotic resistance

Major Factors Contributing to Emerging Infections: 1992 1. Human demographics and behavior 2. Technology and Industry Economic development and land use 4. International travel and commerce 5. Microbial adaptation and change 6. Breakdown of public health measures Institute of Medicine Report, 1992

More Factors Contributing to Emerging Infections: 2003 7. Human vulnerability Climate and weather Changing ecosystems Poverty and social inequality War and famine Lack of political will Intent to harm Institute of Medicine Report, 2003

Emerging Infections: Human Demographics, Behavior, Vulnerability More people, more crowding Changing sexual mores (HIV, STDs) Injection drug use (HIV, Hepatitis C) Changing eating habits: out more, more produce (foodborne infections) More populations with weakened immune system: elderly, HIV/AIDS, cancer patients and survivors, persons taking antibiotics and other drugs

Emerging Infections: Technology and Industry Mass food production (Campylobacter, E.coli O157:H7, etc…) Use of antibiotics in food animals (antibiotic-resistant bacteria) More organ transplants and blood transfusions (Hepatitis C, WNV,…) New drugs for humans (prolonging immunosuppression)

Organ Transplantation Year-end Waiting Lists vs Organ Transplantation Year-end Waiting Lists vs. Transplanted (kidney, liver, pancreas, heart, lung) 70,000 60,000 50,000 40,000 30,000 20,000 10,000 Source: UNOS CDC

Emerging Infections: Economic Development, Land Use, Changing Ecosystems Changing ecology influencing waterborne, vectorborne disease transmission (e.g. dams, deforestation) Contamination of watershed areas by cattle (Cryptosporidium) More exposure to wild animals and vectors (Lyme disease, erhlichiosis, babesiosis, HPS,…)

Emerging Infections: International Travel and Commerce Persons infected with an exotic disease anywhere in the world can be into major US city within hours (SARS, VHF,…) Foods from other countries imported routinely into US (Cyclospora,….) Vectors hitchhiking on imported products (Asian tiger mosquitoes on lucky bamboos,….)

Emerging Infections: Microbial Adaptation and Change Increased antibiotic resistance with increased use of antibiotics in humans and food animals (VRE, VRSA, penicillin- and macrolide-resistant Strep pneumonia, multidrug-resistant Salmonella,….) Increase virulence (Group A Strep?) Jumping species from animals to humans (avian influenza, HIV?, SARS?)

Emerging Infections: Poverty, Social Inequality, Breakdown of Public Health Measures Lack of basic hygienic infrastructure (safe water, safe foods, etc..) Inadequate vaccinations (measles, diphtheria) Discontinued mosquito control efforts (dengue, malaria) Lack of monitoring and reporting (SARS)

Emerging Infections: Intent to Harm Bioterrorism: Anthrax in US 2001 Bio-Crimes: Salmonella in OR, Shigella in TX. Potential agents: Smallpox, Botulism toxin, Plague, Tularemia, ….

Infectious Disease Ecology Epidemiology: the study of the causes of diseases and injuries to humans −What causes disease? −How do you identify the causes? −Mechanistic Disease ecology: the study of causes of emerging diseases to natural populations and communities; - Spatio-temporal patterns of diseases −Why do the patterns of disease occur as they do? −Conceptual: what variables are important?

Types of Infectious Human Diseases Infectious Disease – illness caused by a pathogenic microbe (bacteria, virus, fungi, parasite, prions (aberrant protein)) Emerging Infectious Disease (EID) – “New, reemerging or drug-resistant infections whose incidence in humans has increased within the past two decades or whose incidence threatens to increase in the near future.” IOM 1992 Zoonotic Disease Vector-borne Disease Non vector-borne

Zoonotic Disease Definition –disease caused by a pathogen that primarily resides in a second species and is transmitted to humans without an intermediary species Examples: rabies, H1N1, many others . . . . . .

Vector-Borne Disease Definition -Infectious agents transmitted to humans through action of another species (often arthropods) Examples: Lyme disease, bubonic plague, WNV, malaria, Rabies, many others . . . . . Also non vector-borne diseases (e.g. Cholera, influenza, HIV-AIDS

Diseases can have 3 stages: Endemic -number of cases maintained in the human population (i.e. each infected person transmits disease to only one other person) Epidemic – excessive rise in number of new cases of infectious disease (i.e. each infected person transmits disease to more than one other person) Pandemic – spread of infectious disease over a large area (global)

Emerging infectious diseases • Usually zoonotic • Appear in areas undergoing ecological transformation • Result from adaptation to new hosts OR • Reemerge as a result of antimicrobial resistance • Increased in the past 2 decades

# EIDs by a) pathogen type, b) transmission type, c) drug resistance, d) transmission mode

EID hotspots -the human factor # EID events 1 2–3 4–5 6–7 8–11 EID events from 1940 to 2004 Nature, 2008

Risks of Different Types of EIDs Zoonotic (wildlife) Zoonotic (non-wildlife) Drug-resistant pathogens Vector-borne pathogens

Trends in EIDs 2008 study published in Nature EID events have risen significantly over time peak incidence in the 1980s (HIV pandemic). 60.3% EID events are zoonotic (which include vector-borne diseases in this study) 71.8% zoonotic diseases originate in wildlife (for example, severe acute respiratory virus, Ebola virus), and are increasing significantly over time. 54.3% EID events caused by bacteria or rickettsia (bacteria that only grow inside living cells), reflecting a large number of drug-resistant microbes EID origins are significantly correlated with socio-economic, environmental and ecological factors (SEE MAP)

Lyme Disease Vector-borne disease Lyme disease is caused by a spiral-shaped bacterium, Borrelia burgdorferi Bacterium is carried by the black-legged tick These ticks move about on mammal hosts such as deer and mice environmental factors that affect these non-human hosts have implications for human exposure to Lyme disease Lyme disease is very serious in the northeast U.S.; if untreated it leads to severe joint and nervous system problems

Lyme Disease Transmission The Lyme disease bacterium, Borrelia burgdorferi, normally lives on mice, squirrels and other small animals. Transmitted among animals – and to humans – through bites of certain species of ticks. In the northeastern and north-central US, the black-legged tick (or deer tick, Ixodes scapularis) transmits Lyme disease. In the Pacific US, spread by the western black-legged tick (Ixodes pacificus). Other major tick species in US have not been shown to transmit Borrelia burgdorferi.

Life cycle of blacklegged ticks Live for 2 years 3 feeding stages: larvae, nymph, adult. Tick eggs are laid in the spring and hatch as larvae in the summer. Larvae feed on mice, birds, and other small animals in the summer/fall. When a young tick feeds on an infected animal, the tick takes bacteria into its body along with the blood meal, and it remains infected for the rest of its life. After 1st feeding, the larvae become inactive as they grow into nymphs.

In spring, nymphs seek blood meals to grow into adults In spring, nymphs seek blood meals to grow into adults. When nymph feeds, it can transmit bacterium to a new host (animal or a human). Most human illness occurs in late spring and summer when nymphs are most active and human outdoor activity is greatest. Adult ticks feed on large animals or humans. In spring, adult female ticks lay eggs on the ground. Deer do not become infected by adult ticks, but deer are important in transporting ticks and maintaining tick populations.

Acorns and Lyme Disease: An Ecological Chain Reaction

Acorns and Lyme Disease: An Ecological Chain Reaction Oaks periodically produce large acorn crops, followed by a few years of poor acorn production. This phenomenon is called masting. Acorns are a high quality food for many vertebrate consumers Masting results in a flush of resources available to wildlife every 2-5 years Acorn production sets off a chain reaction that affects the populations of gypsy moths (an introduced forest pest that defoliates forests), and black-legged ticks (vector of Lyme disease)

In mast years, white-tailed deer specialize on acorns and are attracted to oak-dominated forests. Autumn is also the peak activity period for the adult stage of the black-legged tick. Deer are the preferred host for adult ticks; In oak forests, adult ticks take their final blood meal, drop off the deer, and lay eggs (hatch the following summer). The density of larval ticks hatching from eggs in summer is highly predictable based on acorn availability the prior autumn. However, these ticks hatch from eggs free of Lyme-disease; Larval ticks that feed on white-footed mice are much more likely to acquire the Lyme-disease spirochete than are ticks that feed on a variety of other vertebrate hosts. Therefore, the white-footed mouse is considered the principal natural reservoir for Lyme disease.

High acorn densities (in mast years) increases the number of white-footed mice and white-tailed deer in oak forests Mice harbor the Lyme disease bacterium. More mice= more Lyme disease Lyme disease infection is higher in summers following oak mast years (high acorn productions) Acorn biomass could be used to predict Lyme disease risk. Mice eat gypsy moth larvae. More mice = fewer/less severe gypsy moth outbreaks. Jones et al. (1998), Science

Zoonotic Diseases

Cholera Vibrio cholerae Gram negative bacteria abundant in freshwater and estuaries around the world waterborne and attach to crustacean zooplankton Toxin alters sodium pump in intestinal cells  fluid loss gastrointestinal disease climatic and environmental factors that affect water sources and ecology of aquatic food webs influence the dynamics of cholera

Copepod Carrying Vibrio cholerae

First Cholera Pandemic Endemic to areas north of Bay of Bengal (Bangladesh and eastern India)

Cholera The Disease Enters from water or food Colonizes small intestine Symptoms: nausea, diarrhea, muscle cramps, shock, severe dehydration Treatment Rehydration therapy, antibiotics Prevention Water treatment Filtration chlorination

World Cholera 2000-01

Why Has Cholera Re-emerged? Deteriorating sanitary facilities as larger population moves into shanty towns Trujullo, Peru – fear of cancer from chlorination so water untreated Use of wastewater on crops Africa – civil wars and drought caused migrations into camps

How Has Cholera Re-emerged? Simultaneous appearance along whole coast of Peru Traveled in ship ballast? Traveled in plankton from Asia? Can remain dormant in local zooplankton (copepods) until triggered by ???

Cholera and El Niño Periodic warming of water near coast of Central and South America Large plankton blooms, especially in coastal waters with nutrients from sewage runoff

Cholera and El Niño Cholera in Bangladesh also seen to fluctuate with El Niño, but with 11 month lag Rita Colwell and multinational group studying link between climate and cholera Satellite and surface data used to show cholera incidence is related to sea surface temperature

Cholera and Sea Surface Temperature

Cholera Antibiotic Resistance Cholera is becoming resistant to several antibiotics

Will migratory birds continue to follow traditional flyways as the climate changes, or will they adapt and perhaps in the process transport avian influenza to new locations? Graphic: UN Food and Agriculture Organization.

Malaria and Climate Vector-borne life-threatening, caused by 4 species of Plasmodium parasites transmitted to people through the bites of infected mosquitoes. A child dies of malaria every 30 seconds. 247 million cases of malaria in 2006, 1 million deaths, mostly among African children. Malaria is preventable and curable. Approximately half of the world's population is at risk of malaria, particularly those living in lower-income countries. Travelers from malaria-free areas to disease "hot spots" are especially vulnerable to the disease. Malaria takes an economic toll - cutting economic growth rates by as much as 1.3% in countries with high disease rates.

Factors that Increase Malaria Transmission rainfall floods proximity of mosquito breeding sites to people types of mosquito species in the area Introduction of mosquito-borne parasite into areas where people have had little prior contact/immunity (causes large and devastating epidemics) mass population movements driven by conflict

Symptoms and Treatment fever, headache, chills, vomiting (10-15 days after infected). Can cause severe illness and is often fatal without prompt treatment. DRUG TREATMENT/RESISTANCE: combination of drugs known as ACTs However, the growing resistance of parasite to these meds is undermining malaria control VECTOR CONTROL: increasing mosquito resistance to key insecticides DDT and pyrethroids, particularly in Africa; a lack of alternative, effective insecticides; changing behaviours of local malaria-bearing mosquitoes, which can result from vector control efforts (as insects move to more hospitable areas).

Net Reproductive Ratio (R0)

Net Reproductive Ratio (R0) R0 < 1, each ‘infection generation’ is SMALLER than the last R0 = 1, each ‘infection generation’ is the same size as the last R0 > 1, each ‘infection generation’ is LARGER than the last; what happens eventually?

Some Estimated Values of R0

R0 What happens to R0 when . . . . . disease results in immediate death to infected individuals? . . . . . vaccination programs are adopted? . . . . . Population density increases? . . . . . People don’t use good hygiene practices (washing hands, covering coughs)

Vaccinations