BICD 136!AIDS, Science & Society!Prof. Hedrick!WLH 2001!Final 7-10 pm Friday, December 19, 2014!Class Website: http://hedrick.ucsd.edu/BICD136!Film password: SH136!Section !Instructor ! ! !Opt!Author !Title !!818124 !Hedrick, Stephen M !HR !Shilts !And The Band Played On! !Hedrick, Stephen M !R !Parham !The immune system!

! ! ! ! ! ! !R !Stine !AIDS Update!

An introduction to all aspects of the AIDS epidemic. Topics will include the epidemiology, biology, and clinical aspects of HIV infection, HIV testing, education and approaches to therapy, and the social, political, and legal impacts of AIDS on the individual and society. !

AIDS, Science & Society!

HIV epidemic!HIV is a lentivirus, a type of retrovirus that came from chimpanzees and developed into a human pathogen in the last century

It will never leave the human species

It kills a type T cell that is essential to many aspects of the adaptive immune system

As these T cells are diminished, the human body is unable to manage environmental microbes and viruses. Death is inevitable

Victims die of multiple infections

HIV has killed at least 30 million people thus far

Deaths in 2011: ~1.7 million With the advent of Highly effective anti- retroviral drugs, people can remain relatively healthy

Lecture 1!Epidemiology and HIV!

Great fleas have little fleas upon their backs to bite 'em, And little fleas have lesser fleas, and so ad infinitum. And the great fleas themselves, in turn, have greater fleas to go on; While these again have greater still, and greater still, and so on Augustus De Morgan Budget of Paradoxes-1872

Epidemiology, why are some diseases successful (widespread), whereas other’s die out. Why are some highly virulent (even lethal), whereas others are benign? What prevents an infectious agent from wiping out a entire species? What evolutionary pressures guide these interactions? Where does HIV-AIDS fit into these concepts?

AIDS in Brief !

•  Caused by the Human Immunodeficiency virus (HIV).!•  Characterized by severe damage to the immune system.!•  An important clue was the development of a lung

infection (or pneumonia) caused by a fungus called Pneumocystis in AIDs patients.!

What is epistemology?!The theory of knowledge, esp. with regard to its methods, validity, and scope. Epistemology is the investigation of what distinguishes justified belief from opinion.!

132. Epistemology (4)!Central problems in epistemology such as skepticism; a priori knowledge; knowledge of other minds; self-knowledge; the problem of induction; foundationalist, coherence, and causal theories of knowledge. Prerequisites: upper-division standing or consent of instructor.!

Philosophy!

A good scientist, like a good detective, uses his or her judgment. Not all possibilities are worth considering, not because they are impossible, or because the evidence at hand rules them out, but because, given what we know about how the world works in general, they seem irrelevant and far-fetched. It's not reasonable to worry about far-fetched possibilities!

Is Science Value-Free?!by ALVA NOË!

Reasonableness, explanatory adequacy, predictive power, simplicity, coherence: these are the stuff of science!

Theories and hypotheses are supported based on data, or falsified likewise. But it is a mistake, sometimes perpetuated by those in science themselves, to say we have "proven" anything to be "true." To avoid those entanglements, we speak in probabilities, giving more of our concerns to those things with higher probabilities than lower probabilities. !--Matthew Bonnan!

What is a parasitic agent? How do they replicate? How do they spread?

Which factors affect the nature of an obligate parasite?

Host population density Network of host interactions: local vs. distant Type of interactions (proximity, direct casual contact, intimate contact)

Biological or cultural behaviors of the host (frequency of intimate contact, concurrent sex, ritual burial of the dead, sanitation) Presence of a vector Host metabolism Environmental temperature dynamics (seasonal fluctuations) Host mechanisms of immunity

SIVcpz is only mildly pathogenic in chimps (close to HIV-1) SIVsm is probably mildly pathogenic sooty mangabey (close

to HIV-2) each is said to have “natural immunity” Either causes AIDs in other apes (like ourselves) or monkeys We will see later that HIV jumped to humans >5 times from

~1920’s 1960’s: end of colonialism…people in Africa move to cities

and become more mobile 1969: American teenager in St. Louis-HIV infected

(discovered later) 1976: July 4th, Tall ships sail into NYC, sailors from all over

the world 1976: Dr. Grethe Rask falls seriously ill in Kinshasa, Zaire

after 2 yrs of weariness, dies in 1977 of unnamed disease 1980: HIV has landed in a highly connected network of the

gay flight attendants and iv drug users (And the Band Played On,

Randy Shilts)

1981: Five homosexual men present themselves at Los Angeles hospitals

Forever more: HIV causes a world-wide epidemic

Six degrees of separation: how does community structure affect disease transmission?

Scale-free, small-worlds network [Barabási & Albert]

Virulence and the course of disease correlates with mechanisms of transmission!

Pathogens transmitted by respiratory droplets require host mobility (e.g. rhinovirus)!

Parasites that utilize an intermediate vector for transmission can immobilize the host and be much more virulent (malaria, yellow fever, dengue, etc)!

Pathogens in diffuse populations, e.g., Herpes viruses in all animals—always chronic, never cleared!

Secondary (reservoir) hosts (influenza, ebola, etc)!

Parasites that are enduring and depend upon the mobility of a healthy host can be much more virulent (anthrax, small pox)!

Venereal transmission-always chronic diseases caused by persistent infectious agents (syphilis, HSV2, HIV)!

Plague time, Paul W. Ewald

Which factors affect the nature of an obligate parasite?

Host population density Network of host interactions: local vs. distant Type of interactions (proximity, direct casual contact, intimate contact)

Biological or cultural behaviors of the host (frequency of intimate contact, concurrent sex, ritual burial of the dead, sanitation) Presence of a vector Host metabolism Environmental temperature dynamics (seasonal fluctuations) Host mechanisms of immunity

Disease Transmission Incubation Contagious period

[time-course of infection] Etiologic Agent

Common Cold respiratory spread 2-5 d <7 d 200+ viruses: rhino; corona; other

Measles (Rubeola)

respiratory spread 9-12 d ~4-9 d Genus: Morbillivirus

Mumps respiratory spread 16-18 d 15 d mumps virus (paramyxovirus)

Rubella respiratory spread 14-21 d 17 d rubella virus (togovirus)

Small Pox respiratory spread 12 d >40 d

(Ordinary) variola major

Bubonic Plague

rsprtry/vector spread 2-5 d 4 d ... Yersinia pestis

Whooping cough

respiratory spread 7-10 d > 21 d Bordetella pertussis

Diphtheria respiratory spread 2-7 d 14 d Lysogenized C. diphtheriae

Chicken Pox respiratory spread 10-21 d 6-8 d varicella (a-herpesvirus)

Influenza respiratory spread 1-3 d 5-7 d influenza A

Cholera water 1-5 d variable Lysogenized V. cholerae

Our favorite modern diseases (neolithic era)

Disease Transmission Incubation Contagious period

[time-course of infection] Etiologic Agent

Common Cold respiratory spread 2-5 d <7 d 200+ viruses: rhino; corona; other

Measles (Rubeola)

respiratory spread 9-12 d ~4-9 d Genus: Morbillivirus

Mumps respiratory spread 16-18 d 15 d mumps virus (paramyxovirus)

Rubella respiratory spread 14-21 d 17 d rubella virus (togovirus)

Small Pox respiratory spread 12 d >40 d

(Ordinary) variola major

Bubonic Plague

vector spread 2-5 d 4 d ... Yersinia pestis

Whooping cough

respiratory spread 7-10 d > 21 d Bordetella pertussis

Diphtheria respiratory spread 2-7 d 14 d Lysogenized C. diphtheriae

Chicken Pox respiratory spread 10-21 d 6-8 d varicella (a-herpesvirus)

Influenza respiratory spread 1-3 d 5-7 d influenza A

Cholera water 1-5 d variable Lysogenized V. cholerae

10,000 years ago - Late paleolithic

Islands of high density populations!Permanent residence!Close contact with domesticated herd animals!Non-existent public health measures!Increased birth rate!

Holocene human ecology!(10,000 BCE to present) The agricultural revolution!

Late Pleistocene human ecology!(60,000-10,000 BCE)!Hunter-gatherers!sparse populations!widely dispersed!constantly on the move!

Disease Transmission Time-course of

infection Etiologic Agent

Head and body lice contact permanent Pediculus humanus

Protozoans various long-permanent Giardia, Entamoeba, Cyclospora, Cryptosporidium, etc

Helminths, eg pinworms contact, oral-fecal weeks to permanent Nematodes, cestodes, trematodes

None in healthy hosts contact permanent Cytomegalovirus (HHV-5) [b-herpesvirus]

mononucleosis Burket’s Lymphoma

contact permanent Epstein-Barr Virus [g-herpesvirus]

Mouth and genital herpes

contact permanent HSV Type I and Type II [a-herpesvirus]

Hepatitis B contact or vertical Newborns, permanent Hepatitis B virus

Syphilis, Yaws, Pinta contact long-permanent Treponemal spirochetes

TB respiratory spread permanent (2%) M. tuberculosis

Paleolithic diseases

Which factors affect the nature of an obligate parasite?

Host population density Network of host interactions: local vs. distant Type of interactions (proximity, direct casual contact, intimate contact)

Biological or cultural behaviors of the host (frequency of intimate contact, concurrent sex, ritual burial of the dead, sanitation) Presence of a vector Host metabolism Environmental temperature dynamics (seasonal fluctuations) Host mechanisms of immunity

What is Epidemiology?!•  Epi means “on or upon.”!•  Demos means “people, population.”!•  Epidemiology is the study of how diseases affect whole

communities.!•  Infectious disease is about HOST-PATHOGEN interactions!•  All living entities are parasitized!•  The nature of the parasite is evolved to fit the host, its

ecology, its co-evolved mechanisms of immunity!

Epidemiology Definitions!•  Endemic—diseases that persist at

a moderate or steady state level within a given geographic area.!•  Epidemic—an unusually high

number of cases in excess of normal expectation of a similar illness in a population, community or region.!•  Sporadic—disease outbreaks that

have no pattern of occurrence in a given time or location.!

Adapted from Gordis, Leon. Epidemiology. Second Edition W.B. Saunders, 2000.!

•  Pandemic—a worldwide epidemic.!•  Morbidity—refers to illness or disease state.!•  Mortality—numbers of deaths correlated with a particular

disease.!•  Incidence—measurement of morbidity; the number of new

cases of a disease that occurs in a specified period of time in a susceptible population.!

•  Prevalence—measurement of morbidity; number of cases in an existing population at a specified time.!

•  Carrier—an individual who harbors the virus but is not infected as measured by serologic methods or by evidence of clinical illness.!

Epidemiology Definitions, cont’d!

•  Mode of transmission—how an infectious disease is spread from host to host!

•  Etiological agent/pathogen—disease-causing agent.!•  Reservoir—where the etiological agent lives, grows, and

multiplies (probably endemic to a particular host).!•  Vector—an animal that spreads an agent from host to host

(e.g., mosquitoes that spread malaria or yellow fever)!•  Communicable period—time period when an infected individual

or animal is contagious and he/she can directly or indirectly infect another person, animal, or arthropod.!

•  Convalescence—the recovery period after an illness.!•  Zoonosis—any infection or infectious disease transmissible

from animals to humans.!

Prevention and Containment of Infectious Diseases: Quarantine!

•  Practice of quarantine is still used today to prevent person-to-person transmission of infectious diseases (e.g., SARS outbreak, tuberculosis).!

•  Isolation!•  Placards!

© National Library of Medicine!

Some diseases are acute. They strike and they resolve relatively quickly!Some diseases are persistent, they are never cleared and cause life-long infection!Some diseases are mild!Some diseases are often lethal!Is there a conceptual basis for these differences?!

Acute, crowd epidemic diseases 10000 BCE - 1491 CE

None

Common Cold

Measles (Rubeola)

Mumps

Rubella

Small Pox

Bubonic Plague

Whooping cough

Chicken Pox

Polio

Scalett Fever

Diphtheria

Typhoid

Hepatitis A

Meningitis

Influenza

Cholera

Disease-causing agents evolve to accommodate the ecology of their hosts: density, mode and frequency of contact…not the specifics of immune mechanisms!!These principles determine the persistence and virulence of the infectious agent !

Smallpox (430 BC? - 1979): Killed more than 300 million people worldwide in the 20th century alone, and a large proportion of the native inhabitants of the Americas Smallpox is the only human infectious disease to have been completely eradicated from nature. It is also the most stable virus known!

Spanish Flu (1918 - 1919): Killed ~50 million people worldwide in less than 2 years Occurred during and at the end of WWI (Barracks, trenches, high density aggregation of people). People sometimes died within hours of noticing symptoms

Black Death (1340 - 1771): Killed 75 million people worldwide and in 4 years (1347-1351), 1/3 of the population of Europe. Greatly changed culture

Malaria (1600 - today): Kills about 2 million people per year, affects about 500 million people per year

AIDS (1981 - today): Killed ~40 million people worldwide, thus far--the topic of this course; since the beginning of the pandemic, nearly 78 million people have contracted HIV and close to 39 million have died of AIDS-related causes.

Top 5 killer epidemics; Caused by? Transmitted by?

Acute - Chronic Infections!Acute Infection!•  Acute infections show

symptoms very rapidly after infection occurs and once the immune response curtails the agent, the symptoms recede. Once a person recovers he or she may be resistant to recurrent infections by the same agent.!

Chronic Infection!•  The infected person

responds to the agent immunologically but does not clear the virus entirely.!

•  Chronic infections require fewer susceptibles than acute infections and so can be maintained in smaller populations. !

•  HIV/AIDS is a chronic infection.!

Crowd-epidemic diseases! Long co-evolved diseases!

Long co-evolved chronic diseases Crowd-epidemic diseases

Disease Vaccine? Disease Vaccine?

Head and body lice NO Common Cold NO

Protozoans NO Measles (Rubeola) YES

Helminths, eg pinworms NO Mumps YES

CMV NO Rubella YES

mononucleosis, Burket’s NO Small Pox YES

TB NO Bubonic Plague Not yet

Yaws, syphillus NO Whooping cough YES

Oral and genital herpes NO Diphtheria YES

HIV NO Chicken Pox YES

Hepatitis B YES Influenza YES

HPV YES Cholera YES

Vaccines

Trade-off theory!•  Extent and speed of pathogen replication

equates with virulence!•  Transmission depends upon replication

and the ability of the host to exist long-enough to spread the infection!

•  Virulence is almost always self-limiting and balanced against transmission!

Figure 02.F01: Population factors that affect epidemics.!

-!

dx/dt = aH - (b + βH)x - Λxy + γz

dy/dt = Λxy - (b + βH)y - ây - vy

dz/dt = vy - (b + βH)z - γz

dH/dt = (a - b - βH)H - ây

birthdeath

infection

Loss of memory

Recovery

Mortality from disease

susceptible!

infected!

immune!

total!

Ray Anderson, 1979!

Imm!

SIR Model of Disease Spread!

Mortalityfrom disease

Pop

ulat

ion

depr

essi

on

Population rate of

increase (d

isease-fre

e)

Equ

ilibr

uim

infe

ctiv

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© Nature Publishing Group1979

Experimental population variation in the face of disease!

Ectromelia (mouse pox)!

Pasteurella muris!No disease!

Observed with

disease!

A=6! A=0.3!

What are factors that control virulence in:!SARS-coronavirus!West Nile Virus-flavivirus!Hantavirus-bunyavirus, haemorrahgic fever!What about HIV, how can it be so virulent and spread so far across the earth?!

Virulence is self-limiting!