Biology of Infectious Disease

Note: Disease is not a causal agent but a product

-AIDS - product -HIV - causal agent -disease symptoms: body response to injury -chiggers itching: response to feeding tube -green: kind of a disease, part of the name of the agent

Definitions of Disease

-An example: the hare, the worm, and the lynx -lynx predation, worm disease disease: time frame, internal, life cycle, size -not totally clear the difference

Global and Local Extinction Due to Fast Synchronization of Patches

-Anholt -spread of phocine distemper virus (PDV) in 25 connected colonies of harbor seals -killed 18,000 seals -models showed: slow increase susceptibles within colonies + very high transmission rates between colonies prevented disease persistence -long-lived harbor seals: not enough turnover for new suscpetibles

Fungi - Major Pathogenic Groups

-Ascomycetes - sexual, nonmotile spores formed in sac-like ascus -Candida (yeast infections), athlete's foot, ringworm (skin infection), chestnut blight -sexual reproduction - hyphae sexual forms contact to form sacs of spores - reach other organisms to become branching hyphae

Pathogens and Parasites

-Broad generalities (but no hard and fast definitions) -pathogens usually thought of as smaller than parasites -micro-parasites (=pathogen) vs. macro-parasites ( = parasites) -endo-parasites (intimate association), ecto less intimate

Mycoplasmal Conjunctivitis

-Caused by the bacterium Mycoplasma gallisepticum -Found in domestic poultry -First sighted in house finches in winter of 1993-1994 -Novel strain infects House Finches -Can cause blindness and mortality -Transmitted by close contact and contaminated feeders -House Finch Abundance Declined After Arrival of Mycoplasmal Conjunctivitis

Why Do We Care About Co-infection?

-Co-infection can alter host health and mortality -HIV-1 and hepatitis C

Modern Discoveries: Girolamo Fracastoro

-Concept of infection from infected to healthy by "spores" or imperceptible particles -Does not assume that spores are organisms (more like chemicals) -Epidemics caused by infections-Three types of infection: direct contact, by "fomites" (clothes, bed linen, etc.), infections at a distance

Hippocrates

-Considered "father" of medicine -Rejected supernatural or divine forces as causation of disease -Strongly argued for the importance of natural causes and rational treatments

What determines the speed of advance of an epidemic?

-Dispersal distance -AND: rate of increase of disease in any one location once it has arrived

Effect of Disease Virulence on Equilibrium Population Size - Mortality

-Mortality (deaths due to disease) vs. Equilibrium Population Size -too low: disease spreads but doesn't control -too high: disease doesn't spread (dies out) -curve with minimum in the middle

Who is Coinfected?

-Older individuals likely to be coninfected by chronic parasites -If parasites share transmission routes, individuals most at risk for one parasite are most at risk for the other -more at risk for syphilis, more at risk for gonorrhea/herpes

Example: Wolbachia Mechanisms

-One of the world's most parasitic microbes -Only transmitted maternally -1. Effects on host: feminization - male offspring become females -2. can lead to parthenogenesis - reproduction without males -3. male killing -4. cytoplasmic incompatibility - infected males are incompatible with uninfected females (lower uninfected population) - both = offspring infected, female infected = offspring infected

Biting Midges

-Oropouche virus -monkeys and sloths and birds in the Amazon -natural reservoir host unknown -outbreaks in Brazil, Peru, Romania -urban, dengue symptoms, short but explosive outbreaks, no vaccine -biting midge: Argentina to Wisconsin, goes through mosquito nets

Consequences of Vaccine Denial

-Personal Belief exemptions ???????????????????????

Example: Malaria

-Plasmodium species -disease of reptiles, birds, mammals -1/2 of world population in 106 countries at risk of infections -life-cycle alternates between man (or other vertebrate host) and mosquito -several but not all mosquito species act as vectors

Number of insect species in British fauna that are predators or parasites

-Predators and grazers: 1,311 -Parasites on plants: 5,941 -Parasites on animals 6,031

Lecture 8

Population Dynamics

Lecture 10

Population cycles and regulation

Disease Dynamics: Spatial and Regional Effects

Regional effects: -Spread of disease from a point source (Traveling waves, control) Endemic diseases on a regional scale: -metapopulation concept

Lecture 6

Transmission

Lecture 3

Who Gets Diseased?

Examples of bacterial diseases in humans

black death, cholera, tubercolosis, bacterial STDs (syphilis, gonorrhea, chlamydia)

Wildlife bacterial diseases

bovine tuberculosis, brucellosis, anthrax, chlamydia, lyme disease, Wolbachia, mycoplasmal conjunctivitis

Joseph Lister

in 1867 emphasized importance of antiseptic surgery

Most hosts have multiple parasites

log number of animals sampled vs. log parasite species richness: linear

Mechanisms of Generating New Variants

mutations and error during replication integration of the segments of the host genome into the viral genome -due to errors during replication and assembly -or during excision of integrated virus from host genome Recombination (during co-infection) -Within molecules: strand switching (replication enzymes switch between two template strands) -Between molecules (in segmented viruses, also referred to as re-assortment)

Diseases Caused By Eukaryotes

nearly all major groups have parasitic representatives and cause disease -fungi: plant and animal diseases -protozoa: mostly animal diseases -helminths: only animal diseases -nematodes: plant and animal diseases

Disease

product of interaction between the host and the pathogen/parasite

β

•(From last time): With density-dependent transmission, the infection rate of susceptible individuals = β*I •β*I*S = absolute number of newly infected individuals per time interval •Note: β itself depends on -Per contact transmission probability -Number of contacts made with a diseased individual -For most diseases (e.g. flu) these are difficult to measure separately

Germ Theory

•1835 Agostino Bassi, Italy, shows that silkworm disease is caused by a fungal infection (Beauvaria bassiana) •Developed theory that human diseases might also be transmitted via living microorganisms •Beginning of the GERM THEORY

Review on the Spanish Flu Reading

•1918-1920 Flu killed ~ 50 million people (more than world war I) •In 2005, the virus was isolated from frozen bodies and the genome published •In 2007 the virus was tested on macaques which died within a week (Kobosa et. al., Nature 2007)

Characteristics of Viruses

•2 major parts: DNA or RNA and protein coat •Obligate intracellular parasites •Inert outside the host •Hijack host's cell machinery to replicate

What About Homo Sapiens?

•2005 count in Emerging infectious diseases 2005: -Lists 1407-58% shared with animals

Other Flu Controversies

•2012: Controversial research: H5N1 virus can be altered (through only 5 mutations) to make it transmissible between mammals through the air has been published •Wild-type of H5N1: greater mortality than Spanish flu •Publication initially blocked by US Government (because of fear of bioterrorist weapons and escape from laboratory) •Scientists successfully argued the benefit > costs (vaccine development and public health strategy) •New U.S. policy on dual-use life science research defines what is permissible by scientists and gov raised new concerns about regulating sci

Contact Rates and Population Size for Different Transmission Modes

•Aerial, soil, waterborne, and non-sexual contact diseases (OIDs-ordinary infectious diseases) •Sexually transmitted diseases (STDs) •Vector transmitted diseases (VTDs)

The SIR Model: Dynamics with Recovery into an Immune Class (R)

•Assume a third class, R, which represent an immune (or resistant) class, that immunity is life-time, and recovery is because of immunity: •St+1 = St - β ItSt •It+1 = It + β ItSt - γ It •Rt+1 = Rt+ γ It •What are the dynamics of this system??? •Requires lots more algebra/calculus but it's doable

Start with simplifications (SI model)

•Assume total population size is constant (common for human epidemiology) •Assume a "micro-parasitic" infection •Assume two classes of individuals -Susceptible = healthy -Infected = also infectious

Cycles: Examples

•Canine distemper virus (CDV) in Serengeti Park •CDV Epidemics in the Serengeti National park -number of lions fluctuates -number non-immune increases due to newborns, decreases with onset of disease

AN EXAMPLE OF IDENTIFYING CAUSE: DISEASE RELATIONSHIPS-PRIONS

•Characteristics-Cause neuro-degenerative diseases (TSE: transmissible spongiform encephalopathy) •E.g. Creutzfeldt-Jacob syndrome and Kuru in humans •Mad-cow disease (BSE), scrapie in sheep, chronic wasting disease in deer, elk, moose

Lecture 10 Conclusions

•Cycles of diseases can be driven by intrinsic and extrinsic factors •Diseases can regulated populations if the pathogen is sufficiently virulent (but not too much) •Assignment: Reading plus watching TED lecture: http://blog.ted.com/2009/08/13/stopping_pandem/ •lecture by Larry Brilliant on stopping Pandemics, guru told him to eradicate small pox, first disease ever to be eradicated worldwide

Epidemiology Terminology

•Disease prevalence -percentage (or fraction) of a population that are diseased •Disease incidence -percentage (or fraction) of newcases of disease occurring during a fixed time period •An epidemic -sudden increase in disease prevalence -An epidemic disease: a disease that shows frequent epidemics -An endemic disease: a disease that is present in a population at a relative constant level for a long time •A pandemic -world wide epidemic

Qualitative Dynamics of SIR Models

•Disease will increase if R0> 1 •BUT: as the disease spreads, there is no return from the resistant class •When resistant class becomes sufficiently large & density of susceptibles gets to low, diseases dies out

Who Gets Infectious Diseases: Mono

-Mono: By age 5: 50%, by 35 : 95% were infected at some point -prevalence highest in college graduates, about 12% of college student convert each year

Chytridiomycota

- no hyphae, transmissible only through flagellated zoospores -Chytridiomycosis

More complications

-"Same" disease caused by different agents -common cold, flu -malaria: caused by 4 different protozoan species, genus Plasmodium -menengitis: infection of the membrane and fluid enclosing the brain -viral, bacterial, fungal cholera: bacteria in fecal matter in water humans (diarrhea) vs. birds (none) - not sure why bird version is called cholera

Proteins only hypothesis

-"infectious proteins": prions do not replicate, but induce other similar proteins to change their structure -Supporting evidence: no virus, bacteria, etc.: particles have been conclusively associated with prion diseases -no DNA or RNA associated with diseases -no immune response to infection -level of infectivity is associated with abnormal sheet form -there is a viral alternative hypothesis (Manuelidis), proteins only more popular

Parasites Alter Interspecific Epidemics by Regulating Populations

-1987-1997: nematode prevents grouse from laying eggs -cycle: population crash, few uninfected repopulate, enough hosts for disease to spread again -parasite also crashes after host crashes -get rid of parasite: population cycle disappears -Reduces transmission of density dependent diseases

Population Dynamics: Cycles: Causes of Cycling

-Externally caused ("environmental forcing") •e.g. arrival of kids at the beginning of school year •e.g. seasonal changes -Entry of new individuals into the susceptible class •Birth of susceptible individuals

Physical "Vectors"

-Fomites: objects touched by humans or animals and on which diseases are transmitted (door knobs, bird feeders)

Population growth rate and AIDS in Africa

-Growth rate of country's population decreases with AIDS prevalence -lowest: Botswana

Coinfection Alters Epidemics via Transmission

-HIV increases susceptibility to malaria, malaria increases HIV transmissibility, both infections increase mortality due to the other, malaria infection decreases sexual contact (anemic) -difficult to say impact on host population scale -reality: fuels spread of both diseases

Example of Host-Pathogen Dynamics

-House finch: Carpodacus mexicanus -Native to southwestern North America & Mexico -1940: handful of birds released in NYC -rapid range expansion of house finches

Heligosomoides polygyrus

-Infection with the nematode Heligmosomoidespolygyrus leads to increased host mortality and lower vaccine efficacy of the malarial parasite Plasmodium chabaudiin mice -indirect positive interaction between parasites -due to immuno-suppression

Examples of Density-Dependent Transmission

-Microsporidians in the water-flea Daphnia: proportion infected decreases with increasing volume (decreasing density) -Hookworm abundance and mammal density: log10 parasitic abundance increases with relative log10 host pop density

Humoral theory of diseases

-Started with Hippocrates -Based on ideas of disequilibria of opposites: -Diseases imbalance between four "humors": Blood, Yellow Bile, Black Bile, Phlegm -Treatments aimed to restore the balance -Dominated medicine for TWO MILLENIA

Patterns of SIR Epidemics

-Susceptibility decreases, resistance increases, infected peaks then declines •Note: # of resistants at end measures individuals that got diseased during epidemic •Note: population still contains susceptibles at the end Note: the higher R0: -The more rapid the epidemic spreads -The higher the peak of prevalence of infected -The shorter the epidemic period -The greater the total number that get diseased

The Concept of R0

-The rate of pathogen increase when rare •"Net reproductive rate of the pathogen" •Mean number of new infections caused by a single infected individual •In our model with density dependent transmission & recovery: R0 = Sβ/γ -The rate at which an infected causes new infections (Sβ) times the average duration of the infection (1/γ)

Cestodes

-parasitic flatworms, inhabit vertebrate guts -adult cestodes lack a gut, absorb nutrients through body surface -attach to host with head-like scolex -complex life-cycles -often suppress immune systems -pork and beef tape worm figure??????

Quantitative Aspects of Vertical Transmission

-Vertically transmission occurs, but is rarely the major mode of transmission Why is vertical transmission not more common? Challenges -if pathogen lowers host fitness than pathogen decreases as well -on average, an individual leaves only one mature offspring (if population is constant - carrying capacity) -1:1 replacement does not spread disease -even then, would require 100% transmission -Vertical transmission is not an effective way for the pathogen to increase its reproductive rate

Horizontal Transmission Modes

-air, water/soil, direct contact (sexual vs. non-sexual), vector, trophic transmission

Koch's postulates weaknesses

-can be useful when a single agent is the sole cause for a disease However, 1. changes in the agent, host, env, may alter whether a disease occurs(disease triangle) 2. single disease may require the interaction of several causes 3. single disease may be caused by several factors 4. A single agent may cause different diseases -Other criteria for cause-effect relationship needed

Chaga's Disease

-caused by trypanosoma cruzi -kissing bug, poops in wound, which irritates and encourages rubbing -8-11 million people infected in the Americas -disease that Darwin had, possibly -Soft wingless insects, about an inch long, crawling over one's body. Before sucking they are quite thin but afterwards they become round and bloated with blood

Protozoa: Sleeping sickness

-caused by trypanosomes -transmitted by insects (biting flies or true bugs) -reverses sleep cycle, hopes that host will lie still in the daytime for biting flies to attack -figure??????????

Parasitic Helminths

-cestodes - tapeworms -trematodes - liver, intestinal, and blood flukes -nematodes - round or hook worms -acanthocephalans - thorny headed worms

Do Co-infections Always Increase Mortality?

-competition for host resources (malaria competition) increases host mortality -direct attacks (bacteriotoxins) decrease host mortality -immune suppression (hiv) increases host mortality

Malaria (Part II)

-complex life-cycle: -sexual (mosquito) and asexual (vertebrate host) reproduction phase - different env -vector and host phase -(sexual reproduction actually occurs in vector) figure??????

More complications (Part II)

-different environments can alter disease -nutrition, stress, or co-infection can determine if hosts become infected -Herpesvirus - often hidden in the host in nervous tissue, triggered by stress -AIDS - infected hosts usually die due to opportunistic infections; reduced immune system

Costs of disease

-difficult to measure in wild populations (animals and plants) -mortality -difficult to find dead animals -indirect costs: reduced reproductive output, loss of body fat or muscles, slower growth and development, more prone to predation

Traveling Waves

-distance vs. numbers -resistant highest at area where it was in the past -healthy highest at distant area -diseased curve peaks in the middle

If Dispersal is Leptokurtic

-distance x vs. y: concentration at center, other clusters outside -Density function: ?????? -Invasion Wave: not parallel, not spreading at constant rate, accelerating, waves more horizontal -advances much faster than with normal distribution with same average distance -advance can be accelerating

Bacteria: Dr. Jeckyl and Mr. Hyde

-e.g. Clostridium difficile -more than 3 million infections in US hospitals per year -related to the bacteria that cause tetanus and botulism -80% associated with healthcare -normally kept in check (e.g. non-active form) by "good" bacteria in the colon -antibiotic disrupts good bacteria, allow C. difficile to cause diarrhea

Virus examples

-ebola, herpes, H1N1, rabies, West Nile, small pox, Spanish flu

Chytridiomycosis

-emerging infectious disease that affects amphibians world wide -invades skin of the adult frogs, in tadpoles only on mouthparts -outcome species dependent -linked to major population declines and possibly extinction -mostly spread through human activities

Examples of Within-Host Parasite Interactions

-establishment and egg output of the barber pole worm is reduced by concomitant infection with sheep stomach worm -negative interaction between parasites, due to direct competition for same host space

Trematodes

-example: ribeiroia ondatrae (Frankenstein) -slows down frogs with extra legs so that birds will eat them -freely moves from snail to tadpole -snail castrated so more energy goes to parasite •Limb deformation in amphibians and infertility in snail •Complex life cycles with multiple hosts and multiple life stages

Fungal Pathogens

-extremely common cause of disease in animals and plants -not as common in humans and other vertebrates (but likely understudied)

Examples of Within-Host Parasite Interactions (Part II)

-feeding of the fish louse ectoparasite increases susceptibility to the pathogenic bacterium Flavobacterium columnare •Direct positive interaction between parasites •Due to mechanical facilitation (i.e. breaking of the skin)

A Community Ecology Framework for Host Parasite Interactions

-free living food web -basal trophic level: primary producers -intermediate trophic level: consumers -top trophic level: predators within host parasite community: -blood, gastrointestinal tract, respiratory tract parasite guilds - intermediate top level - immune system ?????????

Why Do We Care About Co-infection? (Part II)

-helminth/microparasite -plans to "deworm the world" -these examples all focus on parasites which interact via "immune-suppression" -how else might parasites interact?

Fungus and Host Behavior

-hijacks host in different areas, e.g. sperm -advanced: hijack neurology, spreads once ants near colony https://www.youtube.com/watch?v=XuKjBIBBAL8

Definitions of Disease (Part II)

-in humans: any semi-permanent condition that has a negative effect on a human's well being -in organisms: any semi-permanent condition that has a negative effect (impairment, interference, or modification) on the performance of "normal functions"

Recombination

-in segmented viruses: several RNA molecules (strands) in one virion, exchanged between viruses during infection -example: influenza has 8 RNA molecules (recombination major factor driving new mergence of "bird flu")

Graphidium strigosum

-infection with the nematode G. strigosum reduced by previous infection with the hairworm T. retrotaeformis -indirect negative interaction between parasites -due to cross immunity -first parasite triggers immune system

Detecting Diseases

-linear: number of host individuals examined vs. parasite species richness -linear: number of citations (log scale) vs. number of diseases ^same for primate parasites

Smallpox Vaccinations More Effective in Smaller Populations

-log population density vs. & vaccination coverage (decrease)????? and log no. of smallpox cases (increase)

Dr. Jeckyl and Mr. Hyde (Part II)

-many bacteria are commensals and even aid in proper digestion -under the different conditions, the same bacteria can cause disease (E. coli. S. aureus) -most bacteria are free-living saprophytes but some are opportunistic parasites -e.g. by invading wounds or sores (e.g. Clostridium tetani, causative agent of tetanus) •Obligate parasitic bacteria only represent a tiny fraction of all bacteria species described

Cycles: sequential epidemics

-measles in England -rabies in red foxes in France

Parasites Alter Interspecific Epidemics vs. Susceptibility

-measles vs. whooping cough -spike in measles coincides with low whooping cough, and vice versa, for both cases and fatalities -cross-immunity that triggers the other

Helminths Characteristics

-metazoan (multicellular) -parasitic worms -complex life cycles with 2 or more hosts -3 billion people affected

Nematodes

-most diverse group of helminths -can infect by penetrating skin, ingestion of eggs, vectors, or intermediate hosts -very common parasites of vertebrates -e.g. elephantiasis, river blindness

Diversity and Specificity of Parasites

-much higher species diversity than in predators -parasites: 494 species with only one host -46 10-50 -predators: 363 10-50 -0 with 0

Transmission

-natural history of transmission pathways -main types of transmission -modeling transmission

Dispersal distriution and invasion speed

-normal distriution - no acceleration time vs. distance -leptokurtic distribution - acceleration advance - accelerating, increasing slope

Prions

-normal form of prion protein is found in nerve cells but exact function is unknown -Abnormal form is folded in "sheets" rather than helices, much more stable than normal form

Annual Spread of Wheat Rust in US

-not a consistent time scale -probably normal model would be fine, unclear which one it is

Sexually Transmitted Diseases

-number of contacts are relatively independent of density -Population density vs. number of contacts: c(N) = c -frequency-dependent transmission

Effect of Recovery from Rinderpest on Population of Wildebeest in Serengeti

-number of seropositive wildebeests decreased after cattle vaccination -population increased, then limited by resources

Hosts are Usually Infected by Multiple Parasites

-on average 46.4% of humans co-infected, up to 73% -on average 46.2% of wild life co-infected, up to 100%

Populations Often Exhibit Spatial Structure

-populations often clumped in space (metapopulations) connected through migration -metapopulation - population of populations -e.g. bighorn sheep population in California - populations in mountaintops -local populations are at risk of extinction -patches can be re-colonized by migration -common in species with patchy habitats, sedentary and localized movement, barriers to dispersal, social organization/behavioral aggregation, anthropogenic mediated fragmentation

Conclusions: Co-infections

-pretty much everything is co-infected -pathogens can either affect each other positively or negatively -hosts can benefit or suffer from co-infection -effects can be direct (e.g. competition for the same host resource) or indirect (e.g. through host immune system) -parasite interactions can cause changes to disease at the host-population scale

Same agent an cause different diseases:

-prions (abnormal proteins that cause neural degeneration) -in cows: loss of motor control and death (Mad cow disease) -in humans: neural degeneration and death (Creutzfeldt-Jacob disease) Hantavirus -rodents none, humans, hemorrhagic fever Herpes -none wildebeest, malignant catarrhal fever in cattle (can't be transmitted between)

Louis Pasteur

-proves that microorganisms do not arise from spontaneous generation, but come from existing microorganisms -e.g. no wine from sterile grape juice -the nail to the coffin of humoral theory

Florence Nightingale

-reduced mortality rate in military hospital from 60% to 1% during Crimean War -cleaning patients, removing poop, etc. -polar area diagram

Endemic Diseases at a Metapopulation Scale But Local Extinction

-regional stability -rust on valerian plants on islands -islands have epidemics at different points, by chance moves to another island -hops around despite going locally extinct

Infectious Agents

-replicating entities that multiply in or on hosts, and can be transferred from host to host -when these agents cause harm to hosts, called pathogens or parasites, used interchangeably -enter host = infected -manifestation of the harm they cause is termed disease

Fungi: Characteristics

-rigid cell wall made of chitin -hyphal mycelium or yeast-like growth -elongated hyphae can grow though host cells -produce sexual or asexual spores -many are free-living saprophytes

Basidiomycetes - sexual spores formed in club-like basidia

-rusts, smuts, bunts, and some opportunistic infections in humans and animals (e.g. Cryptococcus can cause meningitis)

White Nose Syndrome

-spreading among bats, spatial dynamics of disease ????????

Anther-smut disease - Microbotryum

-technically an STD -fungus takes over the reproductive structure of the flower and spores carried from flower to flower by pollinators -host = white campion (silene latifolia)

Some other rules

-the cause (agent) should be distributed in the population similar to the disease -freq of disease should be higher in the exposed hosts -temporally the disease should follow exposure to the cause -other causes should be ruled out ?????

Even Viruses Get Sick

-the virophage as a unique parasite of the giant mimivirus ????????????

Simplified Human Parasite Community

-top trophic level: antibody response <-> TH1-TH2 tradeoff -intermediate trophic level: parasite/parasite guilds -basal trophic level: host resources -tangled web of pathogens ?????????????

Parasitic Protozoa

-unicellular organisms -can be intra- or extracellular parasites -can be host specific or very broad

Bacteria

-unicellular prokaryotes -no mitochondria, unbound circular genetic material (DNA) -intracellular or exra-cellular parasites -asexual reproduction major mode of replication

The Problem: Defining Pathogens and Parasites

-victim fitness vs. number of victims attacked in a life stage -predators need more than one prey in a lifetime -victim fitness = 0; either dead or incapable of reproducing -intensity dependent: does the disease get worse the more agents you have (initially) -doesn't matter for flu because it multiplies exponentially -ticks: intensity dependent -table?????????

Ecological Importance of Viruses

-viruses important ecological player in natural and human populations, and agricultural systems -introduced viruses often generate major epidemics

Consequences of Interactions for Epidemics

-within-host interactions can change disease spread -lifetime transmission of a parasite in a host is -transmission rate/(mortality rate + recovery rate)

Recombination Steps

1. dual infection (coinfection) 2. uncoating of segmented virus genomes 3. replication of genome segments 4. assortment of genome segments 5. progeny virus with independently assorted genome segments

The Course of BSE Epidemic in the UK

1986-2000 -first verified case of BSE, feed ban introduced, SBO ban -peak of clinical occurrences -mammalian MBM ban, food security assured SBO = specified bovine offals (brain, spinal cord, thymus, tonsil, spleen, and intestines from cattle >6 months of age); MBM = meat and bone meal

Probability of OID infection for susceptible host:

= cN* (I/N) * ε = c* ε* I = β*I

Why Study Infectious Diseases?

>32% of annual human deaths worldwide are the direct result of infectious disease (500 people will die during this lecture) -90% from developing countries -68% of all deaths in Africa Result: high economic cost Why do we seem to see an increase in infectious disease emergence in recent years?

White Nose Syndrome in Bats

????????

"reading" assignment:Watch movie about the role of Chytridiomycosisin global amphibian decline: •http://www.pbs.org/wnet/nature/episodes/frogs-the-thin-green-line/video-full-episode/4882/

?????????

R0 for 2014 Ebola

????????? Ebola 1-2 people vs. Pertussis 12-17 and Measles 12-18

Grouse Treated with Nematicide

??????????

The Disease Triangle

A successful interaction requires: -an infectious Agent, an appropriate Environment, a susceptible Host -A disease is determined by the interaction of Host + Environment + Agent

Ignaz Semmelweis

Austria, 1847 -childbed fever transmitted by physicians themselves, but could be prevented by antiseptics -hated by doctors, accused of being mentally ill

Plant Diseases

Crown gall (agrobacterium tumefasciens -widest host range of all plant pathogens -transfer parts of its DNA to the plant's genome causing tumors (galls) and changes in plant metabolism -Used for genetic engineering of plants (e.g. tolerance to herbicide)

Female to Offspring Transmission

Cytoplasmic -many vector borne diseases in the vector (e.g. West Nile Virus) Transplacental -HIV (low percentage 1-2%) Perinatal (during birth) -HIV, gonorrhea, chagas (potentially) -monarch butterfly protozoan Postnatal -HIV through breast feeding (20%) -seeds under parental trees

If Dispersal is "Normal" Distributed

Density Function k(x): origin vs. Estimated density Invasion Wave: -Progression of invasion vs. Population density (proportion of infected hosts in the population) -start off with one individual, moves up vertically over time -rate of advance of epidemic is constant and depends on both R0 and D, average dispersal distance

Frequency vs. Density Dependent Disease Transmission

Density dependent -Threshold population density for disease increase -Always hosts left at end of epidemic -Disease cannot drive host to extinction Frequency dependent -NO threshold, disease can invade at arbitrarily low host density -Can infect all susceptible host in the population -Can drive host to extinction under certain conditions

Koch's postulates

Developed to establish relationship between an agent (cause) and a disease (effect) 1. The agent must be present in every case of the disease 2. The agent must not be found in cases of other diseases 3. The agent must reproduce the disease when introduced experimentally into the host 4. The agent must be recoverable from experimentally infected hosts

Variation in Viruses

Different "strains" •Historically often identified serologically-"serotypes" -Belong to same "serotype" if cross react immunologically (recognized by same anti-bodies) •Nowadays phylogenetic analysis reveals huge number of variants - e.g. HPV-causative agent of cervical cancer, HIV •Each "strain" itself has numerous variants (true for all organisms actually)

Lecture 7

Disease dynamics and epidemiology

Examples of R0 of some human pathogens

H1N1: R0 = 1.2-1.6 Basic influenza: R0 = 1.5-3

Vaccine Denial and Common Myths

Flu vaccines: •makes you sick •contain dangerous ingredients •cause Alzheimer's disease or hurt children development (by breaking blood brain barrier) •don't work •I'm okay with getting the flu (but others aren't)

Lecture 12

Multi-pathogen systems

Mechanisms Generating Variations in Bacteria

Mutation -errors in replication -transposons: DNA that moves around and causes mutations) Recombination: -transformation: uptake of exogenous (naked) DNA -transduction: accidental transfer of bacterial DNA by viruses -conjugation: transfer of bacterial DNA via conjugative plasmid

OID Transmission

N vs. number of contacts: linear C(N) = cN Often called "density dependent" or "mass action" transmission

Causes of Disease

Non-infectious: internal or external conditions -e.g. dev abnormalities (many cancers) -genetic abnormalities -nutrient or vitamin deficiency (scurvy) Infectious: caused by infectious agents

Vector Transmitted Diseases

Passive: vectors serve simply as carriers -flies transmitting pinkeye - moving it around, but not integrated in life cycle Biological - complex life-cycles of pathogen -not always clear who is vector and who is host -Definitive host: where gametes fuse should be host - mosquitoes for malaria (not consistent in lit) -Primary host vs. secondary host - meaning is context dependent

Lecture 11

Spatial Dynamics of Disease

Major Types of Transmission Pathways

Vertical transmission - transmission between generations from parent offspring Horizontal transmission - transmission within a generation, independent of their parental relationship

Vertical Transmission

Vertically transmitted diseases must therefore: -additional horizontal mode -or increase the number offspring or reproductive output of its host (relative to uninfected host) -but increasing reproductive success of host makes the pathogen a mutualist (by definition), but not always

Lecture 4

Virus and Bacteria

Decomposing Transmission

What factors determine the probability of susceptible hosts becoming infected: -number of rate of total contacts (C(N)) -fraction of those contacts that are with diseased individuals (I/N; I = infected; N = total number of individuals in population) -given that contact has been made with a diseased individual what is likelihood of infection (ε) -probability of infection for a susceptible host is: C(N) * (I/N) * ε

Lecture 2

What is a disease

Viruses: Examples and Importance

•Ecological importance - Nature (August 28, 2008): Deep sea Viruses infecting protozoa affect global carbon cycle •In deep sea sediments large amounts of carbon stored in bacteria •Virus kills >80% of bacteria, releases vast amounts of carbon into an otherwise nutrient limited ecosystem -Viruses interact with climate change: indirectly control biogeochemical cycles, carbon sequestration of oceans, and gas exchange (Danovaroet al. 2010)

Disease Dynamics and Epidemiology

•Epidemics •Simple models of disease spread ????????

Fraction to Be Vaccinated for Different Diseases

•Fraction is high but not 100%! •Fraction to be vaccinated depends on R0 which also depends on the population size -smaller populations need lower proportion vaccinated

How Many Should Be Vaccinated

•Goal is to reduce S (by converting them to R) such that: R0≤ 1; i.e. S < γ/β (given density-dependent transmission ) •If population size N = S+R (few diseased), then S=N-R→ N-R < γ/β→ R > N-γ/β •To get fraction to be vaccinated, divide by N, → R/N > N/N -γ/βN •If all population susceptible, then N = S so fraction to vaccinate = 1-γ/βS = 1-1/R0

Applied Epidemiology: Vaccination

•Goals - Protect the individual from infection -individual immunity -Protect the population from an epidemic -"Herd immunity" •Generates conflicts -Good of the individual vs. good of the group -Individual 'benefits' decline with group success

Some Examples: Metschnikowia Bicuspidata

•Host ingest fungus •Needles pierce gut •Needles extend branches into body cavity •Once in body cavity, fungal cells multiply until host bursts

Virus Terminology

•Individual particles = virions -Virions consist of a nucleic acid _core_ and protein _capsid_; may contain other proteins in core -May or may not be coated with membrane from host cell (enveloped vs. non-enveloped) -Virion production and release may or may not be cell lysis (lytic vs. non-lytic)

Important Factors in Vaccination Programs

•Low R0 •High vaccine coverage•High vaccine efficacy •Highly visible and immediate disease symptoms (for target programs) •Social circumstances to make a convincing case

Summary of Protozans and Helminths

•Many pathogens have very complex life-cycles -the idea that parasites are "reduced free living forms" is not necessarily true •Complex life-cycles make pathogens more vulnerable to intervention at different points in life-cycle (and more difficult to model) •Can modify behavior of hosts to aid transmission

Cycles: Multiple Factors

•Measles cycles caused both by entry of susceptibles & environmental forcing (of β) -Incidence in England and Wales from 1948-1982 -Every two years, at start of school year -national immunization program decreases number of cases in cycle

R0 - Net Reproductive Rate

•Number of new cases that become infectious in a population of susceptibles ... Here R0 = 5

Protozoa: Take Home Points

•Often vector transmitted •Complex life-cycle •Can initiate behavioral changes in host •Comprises many dangers to human health

Effects on Host Population Size

•Pathogens can regulate host density if disease reduces host fecundity or increases mortality •Disease is said to be virulent if it is harmful •In general (plants and animals) this means that it reduces total reproductive success (RS): RS=birth-deaths •Virulence measure = (RS of healthy-RS of diseased)/RS healthy (proportional reduction in RS)

Frequency Dependence and Threshold for Increase

•Rate of change of infecteds:ΔI = It+1 -It= β StIt/Nt-γ It •Positive (ΔI >0) if βSt/Nt-γ > 0 •If disease is rare then St=Nt, so disease will increase: if β -γ >0 •Or with some rearranging: if R0= β/ γ > 1 •No threshold density for disease increase

Dynamics with Frequency-Dependent Transmission (e.g. STDs)

•Remember: with frequency dependent transmission: Infection rate of susceptibles depends on frequency (I/N) not density of diseased individuals = β I/N •Rewrite SI equation as followsSt+1 =St -β StIt/Nt+ γ ItIt+1 = It+ β StIt/Nt-γ It

The Basic SI Model: Symbols

•S= # healthy (and susceptible) •I= # infected (and infectious) •N = S + I = total population •Prevalence: I/N •β: disease transmission coefficient - The rate at which individuals become diseased

Parasitoids

•Somewhere in the middle between parasites and predators •Usually insects •Example: the horrid phorid: ant decapitating flies

Spatial Distribution Conclusions

•Spread of disease from sources follows statistically predictable patterns •Average distances of dispersal not a good estimate of spread (seriously underestimates!) •Spatial "clumping" can stabilize dynamics of local populations are asynchronous •Accounting for spatial structure has important implications for disease management and conservation

The Basic SI Model

•St+1 = St - β (St)It •I t+1 = It + β (St)It •ΔI = I t+1-It = β(St)It •Always positive •Simple outcome - everyone becomes diseased •Assumes diseased individuals don't recover!

Host-Pathogen Dynamics: Population Effects (Adding Birth and Death Rates)

•St+1 = St - β StIt + γIt + bSt + b'It - dSt (+ births -normal deaths) •It+1 = It + βStIt - γ It - (d+ δ) It -( normal deaths + deaths due to disease) •R0 = βS/(γ + d+ δ)

Summary Lecture 3

•The majority of organisms are parasitic and/or cause diseases: "Diseases are like the stars the more you look the more you see" •Parasites are generally more specialized than predators •Establishing the relationship between an infectious agent and a disease is often complicated due to the interaction of host-agent-environment

Review: Important Things to Keep in Mind about Viral and Bacterial Pathogens

•Viruses: Host dependent, rapid recombination of genes •Bacteria: Many bacteria don't depend on human hosts, only become pathogenic in certain circumstances

Interpretation of R0 values

•When R0 = 1, one diseased individual produces only one diseased individual over the course of its infection •R0 must be > 1 for pathogen to spread and invade host population •When R0 < 1 then pathogen decreases & cannot invade the host population -Vaccination goal is to get R0 < 1

Frequency-Dependent Transmission

•Works well for STDs and vector transmitted diseases •Probability of infection for susceptible host: = c * (I/N) * ε = c* ε* (I/N) = β* (I/N)

Dispersal Distribution

•the probability of a pathogen arriving at a particular distance from a point source -Two types: •Normal distribution (bell shaped curve-random movement) •Leptokurtic distribution (sharper peak with longer tails)

Viral Taxonomic Diversity

•~4,000 virus species recognized in 71 families •Classification: RNA or DNA viruses, different replication sites (nucleus or cytoplasma), different capsid morphology •Common DNA viruses: Poxviridae (smallpox, monkeypox), Herpesviridae (HSV1, HSV2) and Papoviridae (papillomaviruses) - Larger, more genes •Common RNA viruses: Flaviridae (yellow fever and dengue), Ortho- and Paramyxoviridae (influenza and measles), retroviridae -Smaller genome, higher mutation rates

The SI Model with Recovery

•ΔI= It(β St -γ) •Also at equilibrium ΔI = 0 •S = γ/ β, = endemic equilibrium, i.e. whole population is not diseased •Prevalence at equilibrium = 1-S/N = 1-γ/ β N graph????????

SI Model with Recovery

•γ= recovery rate (i.e. disease is short lived; for now lets assume no immunity after recovery) •St+1 =St -β ItSt + γ It •I t+1 = It + β ItSt - γ It •ΔI = I t+1-It = It(β St -γ) •Positive (ΔI > 0) if β St -γ > 0 or if St > γ /β there is a threshold density for disease to increase = St > γ/β •Or with a bit rearranging: if R0 = β St / γ > 1