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Introductory Comments

Definition of Disease

Types (Infectious and non-infectious)

Link to Society?

Disease and Society Linked

Self-preservation and cohesion

Universal sensitivity to certain diseases

Common enemy

Outcomes

Advances/progress

Other Effects of Disease on Society

Behavior (e.g.HIV)

Policies

Outcomes of Wars

Religion (e.g. Christianity and Smallpox)

Economic Effects

Bottom Line: Diseases have shaped the World

History of Medicine

Focus: Western Medicine (800-50 BC)

Fifth Century B.C. Greece Three Types of Healers

1)Physician-Seers

Combined Magic and Drug Treatments 2)Wound Healers

Battlefield Trauma

3)Medical Dietetics

Athletic Trainers

Father of Western Medicine: Hippocrates

Father of Western Medicine: Hippocrates  “ Hippocratic” Medicine -400B.C. How does the environment affect health

Hippocratic” Medicine-400B.C.

How does the environment affect health and disease?

The importance of balance: Body humors

Blood

Phlegm Yellow bile

Imbalance
Imbalance

Black bile

Disease

Treating Imbalances

Conservative approach Diet

Rest

Exercise

Limited drug use

Herophilus (330-260 BC)

Erasistratus (330-255 BC)

Herophilus (330-260 BC) Erasistratus (330-255 BC)  Greek empire spreads (Alexander the Great) from Northern India
Herophilus (330-260 BC) Erasistratus (330-255 BC)  Greek empire spreads (Alexander the Great) from Northern India

Greek empire spreads (Alexander the Great) from Northern India to France to Iraq

Inhabitants (Hellenistic-Greekish)

India to France to Iraq Inhabitants (Hellenistic-Greekish) Inferior?!!! Point: Unwilling subjects for human

Inferior?!!! Point: Unwilling subjects for human dissection

Results:

Circulatory and Nervous Systems, Eye, Female Reproductive Organs, and Physiology

Roman Medicine 250 BC to 200 AD Galen (129 to 216 AD)

Background (Galen) Extraordinarily wealthy

to 216 AD)  Background (Galen) Extraordinarily wealthy Medical Education (Hippocratic view) longest known (age

Medical Education (Hippocratic view)

longest known (age 16-28 yrs.)

Cultured

Experience

Travel

wealthy Medical Education (Hippocratic view) longest known (age 16-28 yrs.) Cultured Experience Travel Man of influence

Man of influence

Galen

Contributions

Animal experiments and dissections Patient involvement in healing (bedside manner) Surgery skill

Early Christianity(300AD)

New Trends (Fall of Roman Empire-Middle Ages)

Healing by church and not by physicians Downside Healing by Prayer, Confessions Laying on of Hands, Exorcism, Miracles Upside

Hostels

Middle Ages (1200’s)

Continued emphasis: Four body humors

Formal medical training and degrees

1st pandemic in Europe: 1348

Outcomes (Sanitation):

Burial regulations

Quarantines

Water control

Cleansing & burning of contaminants

1600’s (Scientific Revolution)

Descartes

Mechanical Theory

Harvey

Revolution)  Descartes Mechanical Theory  Harvey Discovers mechanism of blood circulation Significance
Revolution)  Descartes Mechanical Theory  Harvey Discovers mechanism of blood circulation Significance

Discovers mechanism of blood circulation

Significance

Descartes’ and Harvey’s Mechanical views contradict

humoral theory of Hippocrates and Galen

1700’s Medical Police  “Enforce health regulations from the cradle to the grave.”  Why?

1700’s

Medical Police

“Enforce health regulations from the

cradle to the grave.”

Why? Health facilitates dominance

e.g. Smallpox and Variolation

Early 1800’s (France)

Population growth and urbanization

French emphasize (3)

1)Hospitals (Paris medical school) lots of patients

2) Hourly observations recorded Diagnosis and prognosis 3) Pathological anatomy Postmortem examinations

Limitations: Causes of disease?

1830’s and beyond

German Medicine

Medical research emphasized

and beyond German Medicine Medical research emphasized Reductionist View (Schwann, Virchow etc.) Body functions

Reductionist View (Schwann, Virchow etc.)

Body functions governed by laws of physics and chemistry Diagnostic Tools

governed by laws of physics and chemistry Diagnostic Tools X-rays, Laryngoscope Weakness Treatment approaches lacking

X-rays, Laryngoscope

Weakness Treatment approaches lacking

Visualize vocal cords

Mid and late 1800’s

Germ Theory of Disease

Miasma-Poisonous air particles cause disease OR Contagion-living parasites cause disease

Which is correct? Louis Pasteur and Robert Koch-Germ Theory Importance:

Living creatures cause infectious disease

1900’s

Microbiology

Infectious agents

1900’s Microbiology Infectious agents Bacteriology -Bacteria cause certain diseases Virology -Viruses cause certain

Bacteriology-Bacteria cause certain

diseases

Virology-Viruses cause certain

diseases

Protection from infectious agents Immunology-guards with great memory

History of Chinese Medicine

1000 B.C.

Premedical Health Care

Well-being of living & non-living ancestors Cause and Cure:

communication with dead

Optimistic View

Premedical Health Part II

Next Premedical Emphasis

Disease cause: Demons

Cures: Release demons (spells & acupuncture)

Pessimistic view

II  Next Premedical Emphasis Disease cause : Demons Cures : Release demons (spells & acupuncture)

Traditional Chinese Medicine

100 B.C.-Present day

De-emphasis on metaphysical health care

Human organism composed of functional units Unit function: store, process and transport ch’i

Disease cause: units inability to manipulate ch’i

units Unit function: store, process and transport ch’i  Disease cause : units inability to manipulate

Diagnosis

Complexion Pulse

Odors

Origin of Disease?

Two schools of thought:

1) Localistic-Ontological (localized)

Disease results from A: Presence of hostile entity B: Body invaded by environmental factor

(e.g. worms, wind, cold etc.)

C: Wars between functional units Pessimistic

Origins continued

2) Holistic view

Systemic correspondence

Definition? (a connection to everything philosophy)

Origin of disease?(loss of NORMAL harmony/balance)

Optimistic

Treatments

Holistic approach

Massage

Diet

Acupuncture

Moxa cauterization

Sexual activity

Treatments Holistic approach Massage Diet Acupuncture Moxa cauterization Sexual activity

Late 1700’s, 1800’s, and 1900’s

Fragmentation of traditional Chinese medicine-

1700’s and 1800’s

Western approaches embraced (e.g. surgery) during

1800’s and 1900’s

Following cultural revolution (1966-1976) Western and Traditional Chinese Medicine coexist

Western Vs. Traditional Chinese Medicine

The West

Four humors

Localized medicine

Invasive procedures

(e.g., surgery)

The East

Ch’i

Holistic & localized Non-invasive

History of Disease

Introduction Staying sicknesses

Wandering sicknesses

Universal tale of woe “White people bring death” e.g. Those affected: American Indians, Hawaiians

Causes of death: Older patterns

Old patterns:

Isolation of people competition for limited resources (hunter-gatherer)

Result:

Death from lack of resources Modern disease incidence low Cancer, Coronary disease, TB, Smallpox

Why did people begin to die more

from infectious diseases?

Change in patterns

Neolithic or New Stone Age (10,000 years ago) Migration

Domestication of animals Appearance and numbers of urban communities Result:

Death from infectious disease, cancer, and coronary disease increases

How do wandering diseases become staying diseases?

The domestication of diseases and the evolution of

coexistence

What are the requirements for coexistence?

Unavoidable interaction between disease and humans leading to… death of “weak” members of human population & elimination of most virulent microbes

History of Infectious Disease:

The European Middle Ages and Beyond

Expansion of Populations in Europe

How possible (3)? 1) farming 2) trade networks (Europe-Middle East) 3) new and larger urban centers

So much dung and filth of the garbage and entrails as well as of beasts killed, as of other corruption, be cast and put in ditches, rivers, and other waters, and also in many other places, within, about, and nigh unto cities, boroughs, and towns of the realm, and the suburbs of them, that the air is greatly corrupt and infect, and many maladies and other

intolerable diseases do daily happen. (Robertson, 1986)

Case in point “maladies and intolerable

diseases” 1346 and 1350

Black death pandemics

Origin: Europe from China

How? Trade routes connected by Mediterranean

Outcome: 1st wave killed 30% of Europe’s people Future waves killed fewer numbers

Close of 1400’s

Wandering diseases become chronic staying diseases in Europe

TB, Gonorrhea, Measles, Mumps, Influenza,

Chicken pox, Smallpox, Scarlet fever etc

Quick, efficient killers become slow, inefficient killers

European Migration to Africa, Caribbean, Americas, Australia, and Hawaii

To Africa

African diseases: “White man’s grave.”

Yellow fever, Dengue fever, Malaria, parasitic

worms

Europe's donation to Africa: Syphilis, TB, Smallpox, Influenza

European Migration

To the Caribbean

Three problems:

Isolated for centuries from others

No domesticated animals

Lack of genetic diversity

Case Study:

Loss of indigenous population

Hispaniola

1492 Columbus arrives

population of 8 million

exposed to European staying

diseases (TB, Influenza* carried by pigs,

pox viruses etc ) Result:

people all sick at once

lack of workers to obtain nutrition people extinguished within 50 years

The Caribbean continued

Similar fates on other islands

Europeans create slaves out of weakened

people

Europeans turn to Africa for slaves

Enslaved Africans arrive carrying different

staying diseases

At present: Descendants of African slaves

dominate the populations of the Caribbean

The Americas: The 1500’s

Europeans arrive creating a similar result: coastal

areas hit hardest (e.g. Mexico)-Christianity spreads

95% of Mexico’s population eliminated within 75

years

Others:

Peru: 93% loss

Nicaragua: 92% loss

California: 98% loss Florida: 95% New England: Extinction of Patuxet tribe--smallpox

The Pacific: Australia to Hawaii

1500’s, 1600’s, and 1700’s

Similar outcomes:

The last region invaded by European explorers

Long voyages screened out smallpox and influenza

TB and venereal diseases were the major offenders

Result:

Australia: 95% of Aboriginal populations die

within 60 years Hawaii: 95% die within 100 years

Cause: never exposed and limited gene pool among

island peoples

To Consider

Invasion of Virgin-soil conditions lead to holocausts in the past

Q: Are migration-caused health disasters now over because virgin land is essentially non-existent? A: NO Mutations create “new” bugs (e.g. HIV and AIDS) Ease and frequency of travel (i.e., bugs hitch a ride)

1700’s and 1800’s

1700’s and 1800’s Cholera  U.S. and Europe Intense Urbanization: Meat Industry Lack of city plumbing

Cholera

U.S. and Europe Intense Urbanization:

1800’s Cholera  U.S. and Europe Intense Urbanization: Meat Industry Lack of city plumbing Laissez-faire Outcome:

Meat Industry

Lack of city plumbing

Laissez-faire

Outcome:

Sanitation programs (plumbing and sewers)

Looking to the Future

What are we to do?

(quiz 2 material starts)

Anticipate and prevent (How?)

Focus and sequence of the course:

Infectious agents (e.g. HIV) Immune system (Defense) Outbreaks of the past (epidemics e.g. smallpox)

Transmission of Diseases (3)

1)Contact transmission:

A) Direct:body contact between individuals

Horizontal (touching) Vertical (Mom to fetus)

B) Indirect:nonliving object (fomite) to individual

Fomite examples: coins, rusty nails etc.

C) Droplets (travel less than 3ft. in air) sneezing, speaking, coughing aerosols (TB) etc.

Transmission of Diseases

2)Vehicle transmission

A)Waterborne

Usually water contaminated

with sewage e.g. Cholera B)Airborne Infectious agents that travel

greater than 3ft. In the air e.g. TB

C)Foodborne Improper cooking & toxins

B)Airborne Infectious agents that travel greater than 3ft. In the air e.g. TB C)Foodborne Improper cooking

Transmission of diseases

3)Vector transmission-transmission by insects

A)Mechanical vectors Infectious agent on insect B)Biological vectors Infectious agent inside insect

by insects A)Mechanical vectors Infectious agent on insect B)Biological vectors Infectious agent inside insect
by insects A)Mechanical vectors Infectious agent on insect B)Biological vectors Infectious agent inside insect

Reservoir Host Effect on

Disease Transmission

Reservoir Hosts (Reservoirs)

An Infected organism that serves as a

“breeding” and potential source of

transmitting infectious disease e.g. Rodents, Humans, Insects etc.

that serves as a “breeding” and potential source of transmitting infectious disease e.g. Rodents, Humans, Insects
Types of Microbes  Viruses*  Bacteria*  Algae  Protozoa*  Fungi  Helminths*

Types of Microbes

Viruses*

Bacteria*

Algae

Protozoa*

Fungi

Helminths*

 Algae  Protozoa*  Fungi  Helminths* * Microbes/Infectious agents highlighted in this course 47
 Algae  Protozoa*  Fungi  Helminths* * Microbes/Infectious agents highlighted in this course 47
 Algae  Protozoa*  Fungi  Helminths* * Microbes/Infectious agents highlighted in this course 47
 Algae  Protozoa*  Fungi  Helminths* * Microbes/Infectious agents highlighted in this course 47

* Microbes/Infectious agents highlighted in this course

47

Introduction to the infectious

agents

Viruses

Infectious particles

Carry 1 nucleic acid type:(RNA or DNA)

Acellular

Obligate intracellular parasites

agents  Viruses Infectious particles Carry 1 nucleic acid type:(RNA or DNA) Acellular Obligate intracellular parasites

Virus components

1) Nucleic acid core (DNA or RNA)

ds or ss

linear, circular, segmented

2) Protein coat (capsid)-protective cover Shapes (3)

Icosahedral

Helical

Complex

Virus components continued

3) Envelope

What?

Lipid layer stolen from host during exit

Where obtained?

Usually from host plasma membrane

Why? Hiding or masking feature

Q: How do viruses replicate?

A: Obligate intracellular parasites

1)Attach to surface of cell

2)Enter

*3)“Use and Abuse”-virus “babies”

made at cell’s expense

*4)Many virus babies leave cell to infect other cells

* Steps which can cause damage

Persistent infections

What?

Infection lasting from weeks, years, or throughout entire life (Hitchhikers) Which viruses?

DNA and retroviruses (RNA)not ordinary RNA

viruses

Result? A) Chronic infections (blisters and warts)

B) Cancer (15%)

How do viruses cause cancer?

Two strategies:

1. Integration causes damage to host DNA

2. Integrated viral DNA contains oncogenes

Result:

Biological clock of cell is disrupted: cell becomes immortal or cancerous

Treatment of viruses

Goal of chemotherapy (e.g. antibiotics) “Smart” bomb targets unique to infectious

agent

Why are viruses a problem? target sites lacking

Virus becomes a part of the host

Significance?

available drugs are toxic (e.g. AZT)

(Film on Ebola)

Immune defense strategy for viruses

(quiz 3 material starts)

Background (2 points)

1) Immune system needs to recognize the invader 2) Problem with recognizing viruses? Viruses “hide” inside cells

Immune defense against viruses

continued…

Q:How can immune system distinguish healthy

cells from problematic cells?

A:The MHC class I proteins and cytotoxic T-

lymphocytes (CTL)

The MHC class I proteins and cytotoxic T- lymphocytes (CTL) Evidence of problem (peptide fragment) brought

Evidence of problem (peptide fragment)

brought to surface

CTL

58

The Human species and new (Emerging)

Viruses: We are the problem

Destruction of Environmental Niches (e.g.Rain Forest)

Why a problem?

Humans stumble across “new”

reservoirs carrying “new” viruses

Drug resistance (e.g. AZT)

Introduction to Infectious

Agents: Bacteria

Unicellular approach to life Shapes (4)

Spherical (Coccus)

Rod

Spiral

Pleomorphic

?
?

Introduction to Infectious

Agents: Bacteria

Arrangements of bacteria

Strept-chains (e.g. Streptococci)

Staphylo-grape-like clusters (e.g. Staphylococci)

Bacteria  Arrangements of bacteria Strept-chains (e.g. Streptococci) Staphylo-grape-like clusters (e.g. Staphylococci)
Bacteria  Arrangements of bacteria Strept-chains (e.g. Streptococci) Staphylo-grape-like clusters (e.g. Staphylococci)

Virulence Factors:

Weapons of destruction

Types of Virulence Factors

Pili (Adherence)

Flagella (Movement) Toxins (Survival)

Capsules (Escape from I.S.)

Enzymes (Movement in host)

e.g. Spreading factor

(Movement)  Toxins (Survival)  Capsules (Escape from I.S.)  Enzymes (Movement in host) e.g. Spreading
(Movement)  Toxins (Survival)  Capsules (Escape from I.S.)  Enzymes (Movement in host) e.g. Spreading
(Movement)  Toxins (Survival)  Capsules (Escape from I.S.)  Enzymes (Movement in host) e.g. Spreading
63

63

Introduction to Infectious

Agents: Bacteria

Antibiotic targets

Cell wall Protein synthesis (ribosomes) Bacteria can overcome antibiotics How? Extremely short generation time

Bacteria can overcome antibiotics How? Extremely short generation time Significance: Resistance to antibiotics can emerge
Bacteria can overcome antibiotics How? Extremely short generation time Significance: Resistance to antibiotics can emerge
Bacteria can overcome antibiotics How? Extremely short generation time Significance: Resistance to antibiotics can emerge
Bacteria can overcome antibiotics How? Extremely short generation time Significance: Resistance to antibiotics can emerge

Significance:

Resistance to antibiotics can emerge

Concepts of bacteriology:

Sharing antibiotic resistance

Plasmids

1 Chromosome

Plasmid

antibiotic resistance  Plasmids 1 Chromosome Plasmid Carry genetic information for resistance  Pili Transfer

Carry genetic information for resistance

Pili

Transfer genetic information for

Plasmid Carry genetic information for resistance  Pili Transfer genetic information for resistance Conjugation

resistance

Plasmid Carry genetic information for resistance  Pili Transfer genetic information for resistance Conjugation
Plasmid Carry genetic information for resistance  Pili Transfer genetic information for resistance Conjugation
Plasmid Carry genetic information for resistance  Pili Transfer genetic information for resistance Conjugation
Plasmid Carry genetic information for resistance  Pili Transfer genetic information for resistance Conjugation

Conjugation

The Human species and new (Emerging)

Bacterial diseases: We are the problem

Antibiotic resistance Hospitals (nosocomial infections) Irresponsible physicians and patients Destruction of Environmental niches

Leads to atypical encounters and disease

e.g. Deer, Ticks, and Lyme disease

Antibiotic Resistance

Introduction Alexander Fleming & the late 1920’s.

» Mold contamination of bacteria

» Zone of inhibitiona weapon?

» Mold contamination of bacteria » Zone of inhibition — a weapon? This “weapon” triggers a

This “weapon” triggers a health-care revolution

Introduction

These “weapons” became known as antibiotics

“A compound produced by a microbe that kills

or inhibits the growth of another microbe.”

Selman Waksman (Discoverer of Tetracycline)

Events in the Age of Antibiotics

** & the rise of superbugs * WHO: One of the 3 greatest threats to
**
& the rise of superbugs
*
WHO: One of the 3 greatest threats to human health
*Causes?
**The Future

Modified from Davies, J. et al. 2010. Microbiol. Mol. Biol. Rev. 74(3):417-433

Causes of antibiotic

resistance

Human activities

» several millions of metric tons of antibiotics

released since the 1940’s.

activities » several millions of metric tons of antibiotics released since the 1940’s.  The biology

The biology of bacteria

Human Activities

7 billion humans need food

» Growth promotion/Prophylactic use in

livestock

(70% of all antibiotics are consumed by farm animals)

Promotes growth, limits disease

use in livestock – (70% of all antibiotics are consumed by farm animals)  Promotes growth,

Human Activities continued…

7 billion humans are treated

Prophylactic & therapeutic overuse and misuse in humans

Complacency, arrogance, misdiagnosis

Example:

in humans  Complacency, arrogance, misdiagnosis Example: Surgeon General, Jesse Leonard Steinfeld “It is time to

Surgeon General, Jesse Leonard Steinfeld

“It is time to close the book on the problem of infectious diseases”

1969

Human Activities continued…

Bacteria have evolved quickly and dramatically to adapt

Activities continued… Bacteria have evolved quickly and dramatically to adapt to this change in their environment.

to this change in their environment. How?

The Biology of Bacteria

Bacteria reproduce quickly (minutes!) Bacteria pick up genes for resistance from other bacteria

The Biology of Bacteria Bacteria reproduce quickly (minutes!) Bacteria pick up genes for resistance from other

Summary of Factors

Human activities

» several millions of metric tons of antibiotics

released since the 1940’s.

The biology of bacteria

activities » several millions of metric tons of antibiotics released since the 1940’s.  The biology

Future: Is it possible to reverse

resistance?

Antibiotics target important functions, such as cell wall

synthesis and gene expression. Therefore…

Resistance to antibiotics usually leads to a decrease in

biological fitness (Resistant bacteria grow more slowly

than non-resistant bacteria).

Conclusion

Susceptible bacteria should outcompete resistant bacteria provided we limit our use of antibiotics on this

planet.

Defense from Infectious

Disease: The Immune System

Innate barriers (4 types) 1) Anatomic barriers

Skin

Normal flora

Mucus and cilia

Disease: The Immune System  Innate barriers (4 types) 1) Anatomic barriers Skin Normal flora Mucus

Innate forms of defense continued

(quiz 4 material starts)

2) Physiologic barriers

pH

Temperature

Complement 3) Cells (phagocytes)

barriers pH Temperature Complement 3) Cells (phagocytes) Neutrophils, Eosinophils, and Macrophages 4) Inflammation

Neutrophils, Eosinophils, and Macrophages

4) Inflammation

barriers pH Temperature Complement 3) Cells (phagocytes) Neutrophils, Eosinophils, and Macrophages 4) Inflammation

Adaptive immunity ( B-cells and T-cells)

B-lymphocytes (B-cells) How do B-cells protect us? (Antibodies) What do antibodies protect us from? Bacteria, Extracellular Virus

Adaptive immunity II

T-lymphocytes (T-cells) Thelper cells

Cytotoxic T-cells or CTL How protect body? Coordination (Th) or lysis (CTL)

Background on Smallpox

Killed 300 million people during 1900’s Currently eradicated How?

Background on Smallpox  Killed 300 million people during 1900’s  Currently eradicated How?

Properties of Virus

Complex Capsid DNA

Properties of Virus  Complex Capsid  DNA

Properties of Smallpox disease

Entry-mouth and nose

Incubation period (7-14 days)

mucous membranes-lymph nodes-

blood-internal organs-blood

Disease phase (14 days on)

High fever (106 degrees F)

Pain and vomiting

Spread to skin with pustule formation

Infectious periods

Incubation phase-coughing and nasal

secretions

Disease phase-skin lesions

Virus infectious for months without host

Exploitation of survival traits General Amherst, American Indians, and early biological warfare

History of Smallpox

10,000 B.C.

Earliest physical evidence-1157B.C.

Egyptian mummies with pustules

Earliest written records-1346 B.C.

Recently there have been persons suffering from epidemic sores which attack the head, face and trunk. In a short time, those sores spread all over the body. They have the appearance of hard boils containing white matter. While some of the pustules are drying up, a fresh crop appears. If not treated early, the patients usually die. Those who recover are disfigured by purplish scars which do not fade until after a year.

Cortez and Mexico-1500’s

Battles with Montezuma and Aztecs Cortez troops reduced by 30%

Aztecs fail to pursue and complete

victory

Why?

Smallpox carried by a slave

Outcomes

Spanish Conquistadors spared-

immunity (i.e., more of a staying sickness for the Europeans)

Aztecs killed Interpretation

Spanish God more powerful than Aztec

Gods

Result?

Embraced Christianity and Spanish culture

Desperate measures Variolation dried scabs inhaled scabs inserted into wounds

Desperate measures

Variolation

dried scabs inhaled

scabs inserted into wounds

Jenner, Milkmaids, Cowpox

and Smallpoxa better way

Observation

Milkmaids get cowpox do not get

smallpox (“protected”)

Vaccines

1.

Inject cowpox pustules

2.

Inject smallpox

3.

Protected

do not get smallpox (“protected”) Vaccines 1. Inject cowpox pustules 2. Inject smallpox 3. Protected

Resistance to Jenner

Medical and Religious leaders

Royal Society of Medicine-England The Church

Support

Political leaders

Thomas Jefferson Napoleon

American Indian Chiefs

World Eradication Plan

WHO-1953 global proposalRaise herd immunity

1970-Twenty African countries smallpox

1971-Brazil free of smallpox

1972-Indonesia

1975-Asia

1976-Ethiopia

1977-Somalia

1980-The World

1971-Brazil free of smallpox  1972-Indonesia  1975-Asia  1976-Ethiopia  1977-Somalia  1980-The World

Why Successful?

No animal reservoirs

No insect vectors

Infection restricted to humans

Infection is rarely subclinical (can’t hide)

DNA virus (Virus is antigenically stable)

Bottom Line:

Eliminate homes--eliminate infectious agent

Are we done thinking about smallpox?

Day 28military soldier

Are we done thinking about smallpox? Day 28 — military soldier Still contagious Film on bioterrorism

Still

contagious

Film on bioterrorism

Yellow Fever

quiz 5 material starts

Horror of 1800’s in America Endemic to West Africa

Brought by African Slaves

» Caribbean slaves devalued

» African slave value increased

History of Yellow Fever: The

Americas

Earliest written record in1648

» (Yucatan and Havana)

Fever

Remission

Fever (Death within 8 days)

record in1648 » (Yucatan and Havana) Fever Remission Fever (Death within 8 days) Jaundice, Abnormal Clotting,

Jaundice, Abnormal Clotting, Black

Vomit

Yellow Fever in the “New World”

1793 (Philadelphia is the capital)

Fleets from Santo Domingo and West Indies

Sickly refugees discharged from boats

Heavy rains during summer months People evacuate city By September, government shuts down

Properties of Disease

Stage 1-High fever (105 degrees F)

Severe joint pain and vomiting

3 days

Stage 2-Remission

Loss of fever and headaches etc.

last less than a few hours

Stage 3-High fever

Organ involvement & hemorrhaging Jaundice and death within 8 days

Yellow Fever, The Louisiana Purchase,

and Napoleon-Early 1800’s

Napoleon (1801)

Plans for American Empire

Controlled parts of

Caribbean

Central America

Mexico New Orleans

North American Midwest to Canada

Haiti

Napoleon continued

Rebellion by African labor force in Santo

Domingo, a “sugar island”—cash crop

Napoleon sends Leclerc and troops

Result?

Leclerc and 27,000 troops die

Black troops suffer few casualties

Leclerc and troops Result?  Leclerc and 27,000 troops die  Black troops suffer few casualties

Reason? Yellow Fever

Outcomes

Because of Yellow Fever

1.

Hopes to control “The sugar islands”

were squashed

2.

Napoleon sells Louisiana territory,

originally intended to provide grain for

workers in sugar islands.

3.

U.S. is a modern “Super Power”

Throughout 1800’s

Populations reduced by 50%

Mississippi

Memphis-1878/1879 epidemic

New Orleans

Properties in common?

Near water

Southern/warm

Common stories

Carts with 8 to 9 corpses in rough boxes are

ordinary sights. I saw a nurse stop one day

and ask for a certain man’s residence

Negro driver just pointed over his shoulder with his whip at the heap of coffins behind

him and answered, “I’ve got him here in this

coffin”

The

The Daily Appeal, August 13, 1878

Memphis-1878

How is this disease transmitted? person-to-person X

food

X

drinking water

X

Unlike smallpox and others

Typical quarantines not working

Clues

Water association and warm climate

Memphis epidemic-1878/1879

Other casualties ?

111 physicians (microbe hunters) in Memphis

72 from other states

60% died

Second group of Microbe

hunters-1900

Second group of Microbe hunters-1900  Jesse Lazear* 1  James Carroll*  Aristides Agramonte* 

Jesse Lazear* 1

James Carroll*

Aristides Agramonte*

Walter Reed *Risked their lives by self-experimentation 1 Died during self-experimentation trials

Discoveries using human

volunteers from Havana

Cause

Infectious agent passes through filters

Transmission

Mosquito-to-person Not: person-to-person

Infectious stage

1st fever stage

Mosquito takes blood meal

filters Transmission Mosquito-to-person Not: person-to-person Infectious stage 1st fever stage Mosquito takes blood meal

Properties of Yellow Fever Virus

Spherical structure with envelope RNA virus

Properties of Yellow Fever Virus  Spherical structure with envelope  RNA virus

Vaccine

Max Theiler

Attenuated yellow fever virus

Nobel prize 1951

Vaccine Max Theiler Attenuated yellow fever virus Nobel prize 1951

Controlled but not eliminated-

Why?

1. Two varieties: urban and jungle yellow fever

Urban controlled by eliminating urban mosquito

2. Other mosquito vectors cause jungle YF

3. Monkeys are reservoirs for jungle YF

Influenza

Influenza Virus

The epidemic of 1918

Nothing else--no infection, no war, no

famine--has ever killed so many in as

short a period.”

Alfred W. Crosby writes in America’s Forgotten Pandemic: The Influenza Epidemic of 1918

Epidemic of 1918

(Spanish Influenza)

The numbers

80% of U.S. war casualties died from

influenza

200K die from England and Wales

230K die from Germany

200K die from France

Epidemic of 1918

450K from Russia 500K die from Italy

257K from Japan

Bottom Line:

One of the worst plagues of all time

Properties of Influenza Virus

(“To Influence”)

Orthomyxovirus

Spherical shape

Helical capsid

7-8 segments of RNA Envelope w/spike proteins

Neuraminadase (NA or N)

Hemagglutinin (HA or H)

115
115

Properties of virus

Three types of human influenza virus: A, B, and C

Influenza A Responsible for epidemics Infects humans, pigs, horses, seals, birds Reservoir-aquatic birds (e.g. Ducks)

Different strains can coexist in certain hosts

Bird (Avian) virus grows poorly in humans

Human virus grows poorly in birds Both grow well in pigs*

NA and HA proteins

Spike proteins

Function:

HA-allows virus to bind to host cells

NA-allows virus to exit host cells

Types in nature:

HA-16 types

NA-9 types

HA and NA proteins and

nomenclature

Naming of strains

H1N2 or H3N4

How does influenza change? (2)

1. Antigenic shift

the result of genetic reassortment that changes spike proteins completely

e.g., (H3N2) to (H2N2)-leads to pandemics 2. Antigenic drift

the result of mutations that lead to subtle protein changes e.g. (H3N2) and (H3N2) are

not completely identicalvaccine protection

is incomplete

Mechanism for antigenic drift

RNA viruses

1. Error-prone polymerases

Mistakes (mutations)-affect spike proteins

2. Lack of proof-reading

Mutations not corrected Bottom line:

Changes to spike proteins are subtle and lead

to IS escape

Mechanism for antigenic shift

Genetic reassortment in pigs

e.g., Pig infected with Avian influenza and human influenza

H2-rest Avian Human H3N2 + H2N2 Avian Human
H2-rest Avian
Human
H3N2
+
H2N2
Avian
Human

Asia:

Humans, pigs and poultry

Impact of antigenic shift

Quiz 6 material starts

Last several pandemics

1890

1900

1918-(Spanish Flu)--virulent

1933-H1N1

1957-H2N2 (Asian flu) replaces H1N1 via shift 1968-H3N2 (Hong Kong flu) replaces H2N2 via shift 1977-Reappearance of H1N1

Strains can come back and cause Pandemics after periods

of “hibernation”—What are the requirements?

Reappearance of H1N1

Requirements/explanations?

1. Memory/herd immunity must fade

2. Virus must persist in nature (2)

A. H1N1 still maintained in aquatic birds unleashed

B. Escape of laboratory source of H1N1

Continuing problem

Despite vaccine

Antigenic

shift

(no one immune, even those vaccinatedcould lead to a pandemic)

Antigenic drift (vaccine protection incomplete)

Plethora of reservoirs (*Aquatic birds)

Properties of disease

Virus replicates in ciliated cells of respiratory tract-nasal passages,

trachea, bronchi

Cells destroyed & loss of cilia defense

Death from

Bacterial superinfection leading to pneumonia

The impact of influenza on cilia

The impact of influenza on cilia

Factors contributing to flu

resistance

Mucus and cilia action of host Lung macrophages

Suboptimal in aged, premature, pregnant,

and immunocompromised, or the smoker

Vaccines

Current strains grown, inactivated &

injected each fall into “at-risk groups”

Challenges? Antigenic drift of the above-illness possible Antigenic shift--illness and pandemic

Final thoughts

Continuing problem (antigenic drift and shift)

1918 revisited? Possible

Older strains maintained in aquatic birds or

Reacquainted via genetic reassortments (antigenic shifts)

Current situation

Pandemic proportions 3.1 million deaths annually

13,000 new infections/day

Over 42 million infected

The Epidemic of the 1900’s

History of HIV and AIDS

HIV-Human immunodeficiency virus

AIDS-Acquired immunodeficiency syndrome

132

History of HIV and AIDS

June 5, 1981 (CA) 5 homosexuals

Opportunistic disease

 June 5, 1981 (CA) 5 homosexuals Opportunistic disease  By 1983, increase in opportunistic diseases

By 1983, increase in opportunistic diseases

Conclusions

Sexually transmitted

Transmitted agent suppresses IS

Gay disease?

133

History continued

Search for infectious agent Applied epidemiology (Who’s at risk?)

Gay disease?

Hemophiliacs

Discovered by French group

135

HIV

Structure

Enveloped virus with spike proteins

RNA nucleic acid core

Preformed enzymes:

136
136

RT, Protease, Integrase

(Targets of AIDS’ Drugs)

Strains of HIV

HIV-1

Strains of HIV  HIV-1 Evolved from SIV in Chimps  HIV-2 (Western Africa) Evolved from

Evolved from SIV in Chimps

HIV-2 (Western Africa)

Evolved from SIV in Sooty Mangabeys

Strains of HIV  HIV-1 Evolved from SIV in Chimps  HIV-2 (Western Africa) Evolved from

137

How could HIV-1 have crossed

species?

1. Hunter theory (Most widely accepted)

SIV transferred to humans as a result of hunting,

killing and eating chimps or from chimp blood getting

into wounds of hunters

138

How could HIV-1 have crossed

species?

2. Oral Polio Vaccine (OPV) theory

Edward Hooper theory explained in The River

HIV transferred iatrogenicaly (i.e., via medical procedures)

A million people in Africa in the 1950’s exposed to

OPV grown in kidney cells from chimps infected with

SIV

Studies of remaining OPV’s used in Africa were

examined for HIV and SIV in 2000samples were

free of these viruses.

139

How could HIV-1 have crossed

species?

3. The Contaminated Needle Theory

The repetitive use of contaminated,

disposable needles in the 1950’s by

poor locales to save money provided SIV the opportunity to cross.

140

How could HIV-1 have crossed

species?

4. The colonialism theory ‘Heart of Darkness

theory’ by Jim Moore

Late 19 th and early 20 th century, much of Africa under colonial control Colonial rule was harshlabor camps with poor sanitation; food was scarce and physical demands were extremeindividuals were fed cheap food, including chimps infected with SIV.

141

When?

1959 plasma sample has tested positive

for HIV

Projection studies suggest HIV was

around in 1930 with a 15 year margin of error. (Argues against OPV theory)

142

How emerge so quickly since

1930’s?

Travel

Blood Industrydonors paidselected

for desperate people

Drug Useavailability of heroin after

Vietnam war—1970’s

Promiscuous sex

143

Does HIV cause AIDS?

Peter Duesberg says no

Koch’s postulates

Correlation 100%

Grow infectious agent in pure form

Inject into host and observe disease

Reisolate and repeat

144

Transmission

Anal sex

Giver infects receiver (“the receiver” gets it)

(Source: HIV in semen)

Receiver infects giver (“the giver” gets it)

(Source: HIV in blood gets inside giver’s penis through sores or

cuts)

145

Transmission

Vaginal sex

Male infects female

Source: HIV in semen

Female infects male Source: HIV in vaginal secretions

Transmission

Oral sex (lower risk) Mouth to penis (the performer gets infected) Mouth to vulva (the performer gets it)not

likely

Penis to mouth (the recipient gets it)

Anus to mouth (1 published case)

147

Transmission and Drug Use

Drug use accounts for 36% of all AIDS

cases in the U.S.

1.

IV Drugs- “contaminated needles”

2.

Noninjection drugs

e.g., crack cocaine smokers 3X more likely to be infected than non-smokerswhy? Trading sex for

drugs/money

148

drugs e.g., crack cocaine smokers 3X more likely to be infected than non-smokers — why? Trading

Mother-to-Child

Studies with infected mothers

26% studies transmitted HIV to unborn child

39% of HIV-Positive women in Nairobi, Africa

have HIV in breast milk

149

HIV and Wisconsin

Total:

Gender:

2011

150 as of June on the rise

(outpacing 2010…36% from Milwaukee)

83% men 17% women

Age stats: 24% were 15-24

Film…And the Band Played on

Disease progression--Quiz 7 material begins

1. Primary exposure (M-tropic)

If Virus can adsorb & penetrate human cell,

2. Virus replicates (Acute symptoms)

3.

Immune response

4.

Latency in infected cells (several years)

5.

Periodic replication with mutations

6.

Th cell HIV (T-tropic virus)

7.

Thelper cells killed <200 Th cells/ul

blood-AIDS

151

Hope?

Resistant individuals?!!!!!! Genetic basis for resistance

1.

HIV needs CCR5 to infect cells

2.

10-14% Caucasians make only 50%

of normal levels-Resist

3. Some Caucasians (i.e., 1%) do not

make any CCR5-Complete resistance

152

Therapy?

Transplants involving stem cells that are

homozygous for the delta 32 mutation.

Gene therapy

153

Does the prevalence of the CCR5 defect

provide evidence that AIDS is an

ancient disease?

Certain populations encountered HIV or HIV- like infectious agent during ancient times

Survival required genetic resistance

(i.e., CCR5 defect)

As it turns out, the Black Death epidemic in

Europe during the 1300’s was responsible for

shaping the prevalence of the CCR5 defect

AIDS may not be ancient, but affected

populations prior to the 1980’s (Serum

samples from 50’s)

154

The Black Death

(Bubonic and Pneumonic plague)

The Black Death (Bubonic and Pneumonic plague) History  Two great pandemics of bubonic/pneumonic plague »

History Two great pandemics of bubonic/pneumonic plague

» 550 A.D. (100million deaths over 60 years)

» Middle ages (30% of Europe dies)

Requirements: rat/flea population explosion

1346  Weather favors rodent population explosion in Mongolia  Disease travels from Asia to

1346

Weather favors rodent population explosion in Mongolia Disease travels from Asia to Europe via trade routes How? Fleas carried in furs 30% of Europe’s population lost

Outbreaks in U.S.

1 st case in U.S. in 1900

Los Angeles in the early 1920’s-Last

case of urban plague

Scattered cases in rural areas: Western

Nevada, Northern New Mexico,

Northern Arizona, Southern Colorado

Properties of bacterium

Yersinia spp.

Rod-shaped bacteria

Three species cause human disease

Focus: Yersinia pestis

Properties of bacterium Yersinia spp. Rod-shaped bacteria Three species cause human disease Focus: Yersinia pestis

Transmission: 3 cycles

1st or natural cycle (Sylvatic plague) Bacteria found in wild rodent reservoirs

Bacteria spreads from rodent-to-rodent

via flea bites

cycle ( Sylvatic plague) Bacteria found in wild rodent reservoirs Bacteria spreads from rodent-to-rodent via flea

Transmission cycles

2nd cycle (Urban or Domestic plague)

Bacteria spread to urban rodents

Death usually results

Fleas seek new hosts

cycles 2nd cycle (Urban or Domestic plague) Bacteria spread to urban rodents Death usually results Fleas

Transmission cycles

Third cycle (Human plague)

Infected flea from sylvatic or urban cycle

bites human

Disease: Sequence of events

Disease: Sequence of events  Bacteria injected into blood via flea bite  Blood to lymph

Bacteria injected into blood via flea bite

Blood to lymph nodes (groin area)

Replicate in macrophages

Inflammatory response & swollen groin lymph nodes (“Bubo”)-

Bubonic plague-1 wk after bite (Fever, chills, and pain)

response & swollen groin lymph nodes (“Bubo”) - Bubonic plague -1 wk after bite (Fever, chills,

Disease: Sequence of events

Bacteria “leak” out of lymph nodes to

blood-septicemic plague

Emboli form-bacteria block blood

vessels (purple/”black” lesions of skin and lung

Lesions erode into air sacs-Pneumonic plague-infectious via aerosol-death

within 2 or 3 days

Mortality statistics

Bubonic or Septicemic plague

(50-75% mortality untreated)

Pneumonic plague

(100% mortality untreated)

Virulence factors

Enzymes that resist complement

Capsules

Iron storage molecules

Clot digestion enzymes (e.g. spreading)

 Enzymes that resist complement  Capsules  Iron storage molecules  Clot digestion enzymes (e.g.

Prevention and control

Vaccine (heat killed and living)

Short-term protection

Improved living conditions

e.g. contact between humans and

rodents reduced

Antibiotics: Streptomycin, Tetracycline, etc.

Tuberculosis:

Properties of bacterium--Quiz 8 material begins

Mycobacterium spp. Rod-shaped bacteria

Many species cause human disease

(Leprosy and TB) Focus: Mycobacterium tuberculosis

167
167

History of Tuberculosis

668 B.C.-1st Written proof 1600’s (Europe problem) Consumption

King’s evil

History of Tuberculosis  668 B.C.-1st Written proof  1600’s (Europe problem) Consumption King’s evil 168

168

History of Tuberculosis

1800’s

Pott’s disease

Epidemic proportions in U.S. & Europe

1% of cities populations die/year

Associated with creative genius

It was the fashion to suffer from the lungs;

everybody was consumptive, poets especially; it was good form to spit blood after each emotion that was at all sensational, and to die before reaching the age

of thirty

Alexander Dumas

169

Cause in the 1800’s?  Vampires (3) Life gradually drained from body “Supernatural” appetite of

Cause in the 1800’s?

Vampires (3) Life gradually drained from body

“Supernatural” appetite of sick

Families of vampires Recourse?

Exhume dead and look for blood in heart

170

Moments of clarity: Robert Koch

Late 1800’s

Moments of clarity: Robert Koch Late 1800’s Identify and isolate infectious agent  Diagnostic stain for

Identify and isolate infectious agent Diagnostic stain for infectious agent

Discovered tuberculin

Identify and isolate infectious agent  Diagnostic stain for infectious agent  Discovered tuberculin  171
Identify and isolate infectious agent  Diagnostic stain for infectious agent  Discovered tuberculin  171

171

Screening techniques

Tuberculin skin test (Tine test) Stain for sputum

X-rays for chest nodules

Screening techniques  Tuberculin skin test (Tine test)  Stain for sputum  X-rays for chest

What happened to TB positive

people?

Sanatoria (late 1800’s)

Rest

Diet

Fresh air

positive people?  Sanatoria (late 1800’s) Rest Diet Fresh air  This quarantine reduced numbers of

This quarantine reduced numbers of

new cases

173

W.W.II

“Magic bullets of chemotherapy” Isoniazid

Rifampin

Ethambutol

Pyrazinamide

W.W.II  “Magic bullets of chemotherapy” Isoniazid Rifampin Ethambutol Pyrazinamide 174

174

Mid 1980’s-present

MDR-TB (resistance to Isoniazid and Rifampin)

Origin?

(Complacency, arrogance, and AIDS)

Recourse?

(2 or more antibiotics for 12/24 months)

Latest threat: XDR-TB & TDR-TB

175

Disease progression

Step 1: Primary exposure

Exposure via aerosol Fine and dry quickly

Alveoli of lungs

Enter macrophages

The usual scenario: Macrophages

unable to kill

bacterium

(Skin-/X-ray-)

2/3 week duration

(Macrophages become infected)

176

Untreated after 2/3 weeks

Disease progression: Two possibilities

Latent/Dormant (1)

Who:

Healthy Immune system

What:

(Macrophages and T-cells respond)

Result:

Infection walled-off (tubercle)

Clinical:

Skin+/x-ray+/- (non-infectious)

Concern:

Life-long hitchhiker

Immunosuppression can lead to PT (Reactivationbacteria start to replicate) Two sources of toxicity:

Replicating bacteria kill infected cells (lysosomal enzymes released) Responding macrophages release toxic products Tubercles can become calcified Clinical: Sputum+ (Infectious), X-ray+ , Skin+

177

Untreated

Disease progression: Two possibilities

Miliary/Disseminated TB (2)

Who: Immunocompromised (e.g. AIDS)

What: Infected macrophage not

contained

Result: Small tubercles throughout body

Clinical: Skin-/X-ray+ (non-infectious by aerosol)

Significance: Reservoirs Outcome: Death

179

Vaccine

Calmette-Guerin (BCG vaccine)

M. bovis mutant injected

50% effective

Tests

Tuberculin sensitivity skin tests (TST’s)

Tests  Tuberculin sensitivity skin tests (TST’s) e.g., Mantoux, PPD, etc.  QuantiFERON-TB Gold Test Results

e.g., Mantoux, PPD, etc.

QuantiFERON-TB Gold Test

Results within 24 hours

Is not subject to reader bias

Is not affected by vaccination

182

Final notes

TB from cows to humans (M. bovis) No longer a problem

Pasteurization TB and poverty DOT (Directly observed treatment)

Cholera:

Properties of bacterium --Quiz 9 material begins

Cholera: Properties of bacterium --Quiz 9 material begins Vibrio cholerae Curved or comma shape Colonizes SI

Vibrio cholerae

Curved or comma shape

Colonizes SI

Cholera (rice water stool) 20L/day

184

History of Cholera

1500’s 1st documented epidemics

(India)

1817-1823 1st pandemic

India to China, Japan, Africa, Europe, Americas

Spread? Increased travel & urbanization 1850’s Sewers in U.S. Cholera no longer a problem

185

Transmission & Epidemiology

Fecal-oral spread (flies and/or foul fingers)

Disease of poor (Sanitation & Crowding)

Far East affected--Why? Monsoon rains (fecal matter in drinking water)

Civil strife

186

Diagnosis

Identify bacteria in stool (10million/ml)

Diagnosis  Identify bacteria in stool (10million/ml) 187

187

Pathogenesis (Bold=Virulence factors)

Portal of entry (mouth)

Large numbers needed to cause

disease in healthy host

Flagellum allows for speedy trip

through stomach

Attach to SI mucosa via pili and adhesins

188

Pathogenesis continued

Mucosa and natural defense?

Rapid cell turnover

Bacterium’s answer? Mucinase

Where does watery stool come

from?

After attaching

Toxin (CT) injected inside SI mucosal cell

(affects G proteins)

Leads to excessive cAMP production by cell

Ions pumped across membrane & out of cell

H 2 O from underlying tissues and blood follows

Result?--one of the most rapidly fatal

diseases known bicarbonate (HCO3 - )from blood lost (blood

becomes acidic)

Heart failure

190

Pathogenesis

Why does the bacterium do this? cAMP provides source of carbon

191

Treatment

IV or oral rehydration therapy (ORT) for self-limiting bacterium

192

Prevention and control

Safe water supply Oral vaccine

Prevention and control  Safe water supply  Oral vaccine 193

193

Shigella

Background

S. dysenteriae

Rod-shaped bacteria

Shigella Background S. dysenteriae Rod-shaped bacteria Causes dysentery (bloody diarrhea) Central & South America

Causes dysentery (bloody diarrhea)

Central & South America

20,000 cases/yr in US Associated with poverty and crowding

Other dysentery-causing microbes?

E.coli, Amoeba

Shigella

Transmission (fecal-oral)

Shigella Transmission (fecal-oral) Water contaminated with feces Flies contaminating food Fomites with fecal matter

Water contaminated with feces

Flies contaminating food

Fomites with fecal matter

Personal hygiene is an important factor

Shigella

Pathogenesis

1. Attach to large intestine epithelial “M” cells

(adhesins*)

2.

Induce their own phagocytosis

3.

Invade adjacent cells by using host

cytoskeleton for movement

4. Macrophages and neutrophils prevent

further invasion

Pathogenesis

Pathogenesis Neutrophil Note: Bacteria attaching to M cells Bacteria phagocytosed Bacteria using the cytoskeleton Role of

Neutrophil

Note:

Bacteria attaching to M cells

Bacteria phagocytosed Bacteria using the cytoskeleton Role of macs and neutrophils

Shigella

Pathogenesis

Cellular death?

Bacterial growth inside cells leads to cell death

Result? Lysosomal enzymes released, killing neighboring cells & blood vessels--blood

Shiga Toxin

Function/role unclear May be produced to get bacteria out of human host

Shigella

Treatment & prevention

ORT

Self-limiting in healthy adults

No antibiotics needed, but do reduce severity and duration Avoid contaminated water

Avoid foods washed with contaminated water

needed, but do reduce severity and duration Avoid contaminated water Avoid foods washed with contaminated water

Shigella

Vaccine

Most effective attempts have involved invasive strains

Problem? These vaccines cause symptoms in patients

Cholera vs. Shigella

Transmission

Cholera

Fecal-oral

Link to poverty Yes

Shigella

Fecal-oral

Yes

Endemic sites

India, Asia, Africa

Central & S. America

Colonizes

SI

LI

Invasive

NO

Yes

Diarrhea

Rice-water

Dysentery (bloody)

Treatment

ORT or IV fluids

Antibiotics and ORT or IV

Toxin

CT

ST

Plasmodium falciparum & malaria

Quiz 10 material begins

History

Hippocrates in Egypt-400 B.C.

10 material begins History Hippocrates in Egypt-400 B.C. Fall of Roman and Greek Empires Civil War

Fall of Roman and Greek Empires

Civil War (25% of admissions)

WWII epidemic in pacific

“Head for the hills and bad air”

202

Plasmodium falciparum & malaria

History continued

1955-WHO & worldwide eradication

102 countries

1976-eradication program collapses

DDT-resistant mosquitoes

Chloroquine-resistant microbe

Political unrest

Farming practice changes

203

Plasmodium falciparum & malaria

Current situation

1.5-2.7 million deaths each year (1 mill are

children)

300 million people in Africa and India infected Economic losses in Africa-$1billion/year

40% of world’s population exposed

Bottom Line: One of the world’s greatest health probs

204

P. falciparum

Type of protozoan

Unicellular microbe

P. falciparum Type of protozoan Unicellular microbe

Plasmodium falciparum & malaria

Life Cycle

Why examine?

Origin of disease

Why so difficult to eliminate

206

Plasmodium falciparum & malaria

Asexual reproduction

Merozoites

falciparum & malaria Asexual reproduction Merozoites All but P. falciparum Merozoites * Liver cells invaded
falciparum & malaria Asexual reproduction Merozoites All but P. falciparum Merozoites * Liver cells invaded
falciparum & malaria Asexual reproduction Merozoites All but P. falciparum Merozoites * Liver cells invaded

All but P. falciparum

Merozoites

*Liver cells invaded

All but P. falciparum Merozoites * Liver cells invaded Rhoptries * RBC Male & Fema Gametocytes

Rhoptries

*RBC

falciparum Merozoites * Liver cells invaded Rhoptries * RBC Male & Fema Gametocytes Sporozoites Bite Human

Male & Fema Gametocytes

Sporozoites

Rhoptries * RBC Male & Fema Gametocytes Sporozoites Bite Human Stage “Definitive Host” Bite Sporozoites

Bite

Human Stage “Definitive Host”

Bite

Sporozoites Bite Human Stage “Definitive Host” Bite Sporozoites reach salivary glands Zygote Mosquito Stage

Sporozoites reach salivary glands

“Definitive Host” Bite Sporozoites reach salivary glands Zygote Mosquito Stage “Intermediate Host” Ingested

Zygote

Mosquito Stage “Intermediate Host”

glands Zygote Mosquito Stage “Intermediate Host” Ingested Infected RBC “Burst” in gut Male & Female

Ingested

Infected RBC “Burst” in gut

Male & Female

Host” Ingested Infected RBC “Burst” in gut Male & Female Gametocytes Mate *source of disease 207
Host” Ingested Infected RBC “Burst” in gut Male & Female Gametocytes Mate *source of disease 207

Gametocytes

Mate

*source of disease

207

Invasion by Rhoptry action 208

Invasion by Rhoptry action

208

Plasmodium falciparum & malaria

Disease

Chills and fever

RBC Lysed & release hemozoin

Macrophages release TNF Fever & chills

release hemozoin Macrophages release TNF Fever & chills  Anemia & Jaundice lysed RBC (anemia) hemoglobin

Anemia & Jaundice lysed RBC (anemia)

hemoglobin degraded=bilirubin

liver damage

209

Immune Evasion

Maturational changes

Anatomical seclusion

e.g. invades sporozoites <60minutes

Circumsporozoite Ag sloughing

RBC lack MHC class I molecules

210

Immunity to malaria

Inheritable anemias e.g. Sickle-cell anemia

Hemoglobin forms “Spears”

“Sickle”

Punctures merozoites

anemia Hemoglobin forms “Spears” “Sickle” Punctures merozoites BLine: “In Africa, the lesser of two evils” 211

BLine: “In Africa, the lesser of two evils”

211

Control?

Vector population (Draining standing water)

Reservoir

New host availability (Deet, minimize exposed skin, Mosquito NETS)

Vaccines

Mosquito approach

Gamma rays mutate parasite inside Infect human volunteers

Memory

212

213
213

Facts

-In humans, vertical transmission to

infants is rare

-Mosquitoes remain infectious for life (2-3

weeks) and bite repeatedly

214
214

Helminths

Two phyla Platyhelminthes

Cestodes

Trematodes

Nematodes

e.g. Ascaris

Helminths  Two phyla Platyhelminthes Cestodes Trematodes Nematodes e.g. Ascaris 215
215
215

Ascaris

A. lumbricoides

Ascaris A. lumbricoides Three rounded lips 18 inches in length (powerful) — 3-6mm wide Originally a

Three rounded lips

18 inches in length (powerful)3-6mm

wide Originally a parasite of pigs (domestication) Targets SI

25% of the world infected

Originally a parasite of pigs (domestication) Targets SI 25% of the world infected Each lip is

Each lip is lined with minute teeth

216

Ascaris

Juveniles penetrate intestinal wall

and enter hepatic portal system

penetrate intestinal wall and enter hepatic portal system  Life Cycle Heart Penetrate Alveoli * Eggs

Life Cycle

wall and enter hepatic portal system  Life Cycle Heart Penetrate Alveoli * Eggs hatch in
wall and enter hepatic portal system  Life Cycle Heart Penetrate Alveoli * Eggs hatch in

Heart

Penetrate

Alveoli*

Eggs hatch in SI

 Life Cycle Heart Penetrate Alveoli * Eggs hatch in SI Eggs ingested on raw fruit

Eggs ingested on raw fruit

Bronchiole tubes Trachea to Esophagus

or vegetable

raw fruit Bronchiole tubes Trachea to Esophagus or vegetable Eggs in soil 200K/day Dioecious life cycle

Eggs in soil

tubes Trachea to Esophagus or vegetable Eggs in soil 200K/day Dioecious life cycle Human=definitive host

200K/day

Trachea to Esophagus or vegetable Eggs in soil 200K/day Dioecious life cycle Human=definitive host *Disease/Death *

Dioecious life cycle

Human=definitive host

*Disease/Death

*Gagging & Swallow

Dioecious life cycle Human=definitive host *Disease/Death * Gagging & Swallow * SI maturation & mating 217

*SI

maturation &

mating

217

Diagnosis & Treatment

1. Ascaris pneumonitis: examination of sputum for Ascaris larvae.

2. Intestinal ascariasis: feces are examined for the ascaris eggs.

Direct fecal film: it is simple and effective. The eggs are readily

found using this method due to significant female oviposition

(Over 200,000 eggs per day). Most widely used. Recovery of adult worms: adults or juveniles found in feces, vomit, tissues etc.

Mebendazole: Prevents worms from absorbing glucose.

218

Ascaris

Disease and/or death

Intestinal obstruction

Pulmonary damage

Choking

Important note:

obstruction Pulmonary damage Choking Important note: Erratic migratory behavior due to crowding and/or limited

Erratic migratory behavior due to crowding and/or limited number of males

219

Worms from young child 220

Worms from young child

220

Ascaris

Transmission

Eggs infectious after 10 years in soil

Eggs resist concentrated HCl Children Garden foods Cockroaches

Night soil used as fertilizer

Night soil is produced as a result of a waste management system in areas without community infrastructure such as a sewage treatment facility, or individual septic

disposal. In this system of waste management, the human feces are collected in

solid form (Honey pots).

septic disposal. In this system of waste management, the human feces are collected in solid form

221

Epidemiology

Worldwide distributionWhy?

1. Simple life cycle.

2. Prodigious egg production (240,000 eggs/day).

3. These eggs are highly resistant and remain viable for years.

4. Social customs and living habits.

5. Mechanism for disposing feces.

222

Ascaris

Final notes

-Unbalanced graduate student

-S.Carolina in 1969 (15%) infected

-German currency and nightsoil -Feed off of semi-digested contents of gut

and/or bite intestinal membrane, feeding off

of blood and tissues -85% of infections are asymptomatic

10,000deaths/year—That’s one effective

parasite

223

Platyhelminthes: Trematodes

(Flukes)

Trematodes

Schistosoma

Blood fluke (certain stages in blood)

224

Platyhelminthes: Trematodes

(Flukes)

Schistosomiasis

Africa, S.America, Carribean

Disease of poor

2nd most devastating disease

200million new infections annually

1 million deaths each year

225

Platyhelminthes: Trematodes

(Flukes)

*source of disease

*Eggs w/spines Feces Copulate for life or Urine Schistosomules migrate to bvessels (bladder, LI, or
*Eggs w/spines
Feces
Copulate for life
or Urine
Schistosomules
migrate to bvessels (bladder, LI, or SI)
Human host
& mature

Invertebrate host and/or water stage

Miracidium stage

in water

host and/or water stage Miracidium stage in water Penetrate human host Swim & Infect Cercariae (swimming)

Penetrate human host

Swim & Infect

stage in water Penetrate human host Swim & Infect Cercariae (swimming) Sporocyst in snail Dioecious life
stage in water Penetrate human host Swim & Infect Cercariae (swimming) Sporocyst in snail Dioecious life

Cercariae

(swimming)

Penetrate human host Swim & Infect Cercariae (swimming) Sporocyst in snail Dioecious life cycle Human=definitive

Sporocyst in snail

Dioecious life cycle Human=definitive host

Intermediate Host

Swim & Infect Cercariae (swimming) Sporocyst in snail Dioecious life cycle Human=definitive host Intermediate Host 226

226

227
Contaminated water 228

Contaminated water

228

Platyhelminthes: Trematodes

(Flukes)

Damage

Spiny eggs lodge in intestines or bladder

T-cells & MO form granuloma

Toxic mediators released by MACS

230

Platyhelminthes: Trematodes

(Flukes)

Worm persists--How?

Motile

Masking in host proteins

Worms do not make more worms

25 pairs in human body

231

Platyhelminthes: Cestodes

(Tape worms)

Taenia

Taenia saginata (beef worm)

Platyhelminthes: Cestodes (Tape worms) Taenia Taenia saginata (beef worm) 234

234

Platyhelminthes: Cestodes

(Tape worms)

I. General information

Worldwide distribution

Undercooked beef, Travel to developing countries, Poor

hygiene, Exposure to livestock

25 year life span Over 60 feet in length

235

Platyhelminthes: Cestodes

(Tape worms)

II. Structure

Scolex (head w/suckers)

Germinal center (neck)

Proglattids (hermaphroditic w/eggs)

236

237
237
237

237

Platyhelminthes: Cestodes

Platyhelminthes: Cestodes (Tape worms) III. Life cycle eggs & proglottids in feces adults Release from shell

(Tape worms)

III. Life cycle

eggs & proglottids in feces

adults

III. Life cycle eggs & proglottids in feces adults Release from shell in SI Ingestion of
III. Life cycle eggs & proglottids in feces adults Release from shell in SI Ingestion of

Release from shell in SI

& proglottids in feces adults Release from shell in SI Ingestion of cysticerci in porterhouse Human

Ingestion of cysticerci

in porterhouse

Human

Cow/Grass

Eggs

Encyst Larvae to muscle

SI Ingestion of cysticerci in porterhouse Human Cow/Grass Eggs Encyst Larvae to muscle Cows & proglottids
SI Ingestion of cysticerci in porterhouse Human Cow/Grass Eggs Encyst Larvae to muscle Cows & proglottids

Cows

SI Ingestion of cysticerci in porterhouse Human Cow/Grass Eggs Encyst Larvae to muscle Cows & proglottids

& proglottids on grass

238

Platyhelminthes: Cestodes

(Tape worms)

Disease

Intestinal obstruction

239
239