Infectious Diseases- Intro and Smallpox

Smallpox: Day 8-12

*Secondary viremia* followed by fever and toxemia -Mouth first, then skin signs and symptoms

Prevalence rate

*Total number of cases* of a disease existing in a population divided by the *total population*

Smallpox: 20th Century

-*Estimated 300-500 million deaths* -Early 1950s: 50 million cases in world each year -1950: killed more than 1 million people in India -1967: still infecting 10-15 million people worldwide, killing 2 million people per year -*1900-1980: killed 500 million people, more than all of wars, 1918 flu epidemic, and AIDS epidemic combined (only malaria has caused more deaths); yet disease prevention around ~200 years*

Smallpox Transmission

-*Inhalation of airborne virus* (primarily via respiratory droplets); rarely spread in air via closed settings such as buildings, buses, and trains/ inactivated within 1-2 days in event of aerosol release -*Prolonged face-to-face contact with infected person (within 6")* -*Direct contac*t with infected bodily fluids or fomites -Can cross placenta (low incidence)

Smallpox: 19th Century

-1800: several hundred people vaccinated including Jefferson and family -1875: *Dr. Willam Osler* (Montreal General Hospital) called smallpox agent *virus= poison in Latin*, he could tell smallpox by smell Remember: Van Leeuwenhoek in 1675- small animals, 1st microbes Pasteur- germ theory 1860 1st virus discovered in 1892

Smallpox History

-Earliest evidence: Ancient Egypt 1157 BC in mummified Ramses V uncovered pockmarked (over 3000 years ago) -Likely emerged in human population ~10,000 BC -International traders spread it throughout Old World during 4th-15th centuries

Challenges moving forward

-Emergence of new infectious diseases -Old infectious diseases increasing in incidence & geographical distribution (West Nile) -Old infectious diseases previously under control reemerging (Cholera in Haiti) -Bioterrorism -Drug resistance -Breakdowns in public health systems & communication between nations (ex. wars)

Smallpox: 16th Century

-European explorers and conquerors brought it to Western Hemisphere (immune, resistant)

Smallpox: Infection

-Infectivity wanes 7-10 days, scabs form over lesions -Infected person contagious until last smallpox scab falls off -3 weeks of hell

Smallpox: 11th Century

-Observation people/ doctors alike knew if you got smallpox and lived- you were immune -Doctors tried to infect patients with milder form (*sowing or buying the pox*) -Risk: mild case in 1 person could be serious in another (leave you disfigured, blind, fatal) -*China-* sowed pox, make powder of scabs (mild cases), patients inhale powder through straw

Advisory Committee on Variola Virus Research (ACVVR)

-US, Western Europe, Russian scientists -Dont need live virus strains to develop vaccines, continuation of DNA sequencing necessary -Live virus needed for animal models and developmental of antiviral agents -Focus on research

Smallpox: Day 3-4 after exposure

-Viral multiplication in lymph nodes -Asymptomatic *primary viremia* -viral spread to spleen, bone marrow, lymph nodes -still don't know you're sick

Advisory Group of Independent Experts (AGIES)

-review smallpox research program, virus no longer needed to develop antivirals, promising drugs, tecovirimat, & brinicodfovir -Focus on public health -AGIES and ACVVR in conflict, so WHO organizing a 3rd committee to arbitrate the 2 perspectives

Smallpox Avg Incubation period

12-14 days (range 7-17 days) Interval between exposure and first symptoms How long until you get sick

James Phipps

1796- 7 years after Jenner; Sarah Neimes (milkmaid) scratched cowpox into the skin arm of 8 year old? 7 weeks later, Jenner inoculated him with smallpox (20x over next 25 years but he remained immune)

Last *Natural* Case of Smallpox

181 years after James Phipps vaccinated, 1977 in Somalia (last case in US in 1949)

Smallpox is still out there

2002 WHO still decides no

Variola (worst, smallpox) Vaccinia *Cowpox *Monkeypox *Camelpox *specific for their organisms but we can still get it, less severe than smallpox

5 Orthopoxviruses that cause infections in humans?

General Transmission Factors

Abiotic environmental factors (wind, water, inhalation of spores, entry into skin) Animal vectors (mosquitoes for malaria & dengue and fleas for bubonic plague)

-Spreading in air increases potential -Survival time in the environment

Affects how quickly an infectious agent can spread through a population

Host factors influence infection

Age, immunization, prior/ coexisting illness, nutrition, pregnancy, emotional state (stress)

Smallpox

Americans try to take Canada from England, American Revolution- Americans die from?

Pox Viruses

Among the largest and most complicated in nature Variola 200+ proteins, many lock together (186,102 DNA bases, ~200 genes) vs HIV has 10!

Vaccines

Born from Jenner's cowpox inoculations Comes from Latin vacca= cow Pasteur came up with vaccines but named them in honor of Jenner (1st documentation of ____)

National Institute of Health (Bethesda, MD)

NIH stands for? Where is it located?

Prodromal

Not notable infectious with smallpox in _____ period; period between appearance of initial symptoms and the full development of the rash

Incidence rate

Number of *new cases* of a disease divided by the number of *persons at risk* for the disease

Variola

One of the largest viral genomes

Francisco Pizarro

Overtook the Peruvian Inca Empire similar to Cortes- via smallpox

Centers for Disease Control (Atlanta)

CDC stands for? Where is it located?

Rash onset till scabs fall off

Contagious with smallpox from?

Epidemic

Disease affecting a large number of individuals within a population, community, or region at the same time Outbreak in an area

Pandemic

Disease occurring over a wide geographic area and affecting a very high proportion of the population Outbreak worldwide (ex. HIV, Spanish Flu) Larger worldwide outbreaks of influenza cause a high rate of death

Airborne

Disease transmission by pathogens are aerosolized and stay infective Ex: influenza, TB

Droplets

Disease transmission by pathogens are in ______ (but don't survive long this way) Ex: sneeze, blood, etc fall or don't hang in the air; ebola, bordetella pertussis

Fecal-Oral

Disease transmission through contaminated water or food (also by not washing your hands, etc) Ex: cholera, norovirus, shigella

Indirect contact

Disease transmission via surfaces or fomites Pathogen survives harsh environment, pick up pathogen from surface/ air Ex: influenza, norovirus

Direct Contact

Disease transmission via touch Pathogen survives best inside the body Ex: HIV, herpesviruses, ebola

Smallpox and measles

Diseases brought over by Europeans that decimated native populations of New World Newcomers invade, colonize without restraint

Emerging and remerging infections throughout the world in recent years

Doctors not really trained for these

Yellow Fever

Europeans died from ____ ___ especially in Haiti (tropical) Napoleon's soldiers dying, sells France's New World holding to Jefferson during LA Purchase Americas avoid war with French, increases slave trade, manifest destiny of western expansion in US

Medical care influence infection

Exposure, skin breach (IV, catheter, endotracheal tube), antibiotics, immunosuppressive drugs

Smallpox

Family Poxviridae Subfamily Chordopoxvirinae *Genus Orthopoxvirus* 200nm-400nm Single linear dsDNA Genome 186 kbp

Cowpox

Fever, nausea, sores hands/wrists Not as serious or fatal, no disfigurement, no blindness Less severe than smallpox, but same genus Also swine pox and horse pox

Primary viremia

From initial spread of virus in blood to 1st site of infection

Presidents who got smallpox

George Washington: Barbados 1751 Andrew Jackson: British army prisoner during American revolution 1781 Abraham Lincoln: possibly from son Tad, quarantined shortly after Gettysburg Address 1863

Edward Jenner

Gloucestershire, England dairy land (milkmaids got cowpox but not smallpox) Towns people knew if you contracted cowpox you couldn't get smallpox (old wives tale) In 1789, he inoculated his 10 month old son with pus from swine pox sore and later with smallpox (Edward Jr immune but was sickly with mild mental retardation and died at 21 from TB) Speculated secondary infection from smallpox vaccine caused problems Didnt publicize it

1st week

Highly contagious with smallpox within the _____ of the rash

Long-term compilation of Variola major infection

Scarring, blindness resulting from corneal ulceration, limb deformities due to arthritis, osteomyelitis (infections in bone)

Lesions in a given area are similar in appearance and feel (dimpled vesicles) Progression is centrifugal; and ends up on the hands and feet Smell Umbilication & dimpled vesicles Hard pustules

Smallpox Major Diagnostic Tools

1966

Smallpox eradication began in? -N. America, Western Europe- indigenous smallpox eliminated but vulnerable to travelers -US spending over $1 million/ year on childhood vaccinations, border surveillance, and quarantines -1947: fatally infected American returned from Mexico, outbreak NYC, emergency vaccination of 6 million people -1961: Pakistani visitor to Britain starts outbreak, requires vaccination 5.5 million -1972: all Yugoslavia quarantined, 20 million vaccinated after man returns from Middle East and starts outbreak Few casualties, one smallpox case could shut down commerce, close cities, and create a financial crisis

Maculopapular

Smallpox has characteristic _____ rash that changes to raised fluid filled blisters

Contagious

Smallpox is highly _______ (less so than measles) -Spreads more slowly & less widely than other viruses -Requires close contact, occurs *after the onset of the rash*, short duration of infectious stage

Eradicated

Smallpox is only disease to be ______; astounding achievement of modern medicine through concerted efforts of global vaccination (save 5 million live annually)

Humans

Smallpox only occurs naturally in _____ experimentally infected crab-eating macaques to have a animal model to wipe it out

Inhalation

Smallpox spread most efficiently by means of _____ (less efficiently by direct contact with scabs or pustular material from skin lesions)

Variola major Variola minor

Smallpox virus

Low

Smallpox virus can survive in environment for *short* period *(90% die in air 24 hours, more if have UV rays)* Small pox is most stable in _____ temperatures and ______ humidity (winter)

Hernando Cortes

Spanish conquistador brought infected slave, conquered Mexico 1520 (*destroyed Aztec empire*) -2 yrs later, 3.5 million Aztec native died, no exposure -Aztecs couldn't believe a Christian god held dominance over their native gods (why were Spanish untouched while they died) -Conversion to Christianity

Air

Spread through the ______ has greater potential for infecting a larger number of individuals than through direct contact (ex. TB)

Epidemiology

Study of patterns, causes, effects of diseases

1979 or 1980

Successful vaccination campaigns led to WHO certification for eradication of smallpox in? Smallpox only human infectious disease eradicated (natural host man, no animal intermediate, does not cause persistent infection)

The total number of people dead, not how fast it kills

The top 8 deadliest diseases are classified by?

1) Malaria (1-2 million/yr; ongoing) 2) Tuberculosis (more than any other; around since 4000 BC) 3) Smallpox (500 million) 4) Spanish Flu (50-100 million) 5) Bubonic Plague (75 million) 6) HIV/ AIDS (25 million; ongoing) 7) Typhus (3 million) 8) Cholera (100,000+)

The top 8 deadliest diseases are?

Bacteria, Viruses, Fungi, Protozoans (ex. malaria), and Helminths (worms)

These pathogens are the leading cause of death *worldwide*; particularly in countries of low income (especially in children)

Smallpox Remains

This disease still remains frozen and protected in CDC and Russia 3 strains all genetically sequenced Ready to grow it fast incase of bioterrorism

Factors influence infection

Travel, environmental degradation, climate Takes 1 person to bring over a disease

Indiscriminate killing

Tremendous morbidity and mortality led to ___ _____ of kings, warlords, tipped balance of power due to smallpox (air transmission didn't care if rich or poor) Took out whole civilizations (Incas, Aztecs) destroyed in a single generation; efforts to ward off the disease affected religion and medicine Directly & profoundly influenced course of human history

False (Ward Churchill fabricated this information 1994-2003)

True or False: US Army gave Native Americans blankets laced with smallpox to take over their land

Blotchy pimples

Variola is latin for?

Pox, Great pox

Variola used to be called the ______, term smallpox 1st used in Britain 15th century to distinguish variola from the _____ _____ (syphilis) Named 580 by Bishop Marius of Avenches, Switzarland

Secondary viremia

Virus has replicated and entered circulation again

Soviet Union & Bioterrorism

WHO has postponed destroying smallpox even till this day Russia *weaponizing and making vats* of it 1st Smallpox weapons factory in Soviet Union 1947 Production line to manufacture smallpox on an *industrial scale* was launched at Vector 1990

World Health Organization

WHO stands for?

Bacterial

You're body has 100x more _____ cells than human cells

Eliminated

Zero naturally occurring cases in a specific country/ region

Diseases

____ changed dynasties, armies decimated by disease

Sign

_____ is objective; can measure it physically/ seen/ heard Ex: blood in stool, cough, rash, fever, etc

Symptom

______ is subjective; can't measure it Ex: pain, fatigue, etc

<1%

______ of all microbes are pathogenic (but don't know for sure) Not all microbes are bad, some are beneficial

Smallpox

_______ infection focused in small blood vessel of skin, mouth, & throat before disseminating

Fomites

contaminated bedding or clothing (inanimate objects or surfaces)

Mortality

Another term for *death*

Morbidity

Another term for *illness* Person can have co-_____ simultaneously Prevalence used to determine level of _____ in a population

Smallpox: Pre-rash stages

Incubation stage Prodromal stage Pre-eruptive stage (blisters non-eruptive_

Old

Infectious diseases are _____ They date back *90 million years* Ex: dental abscess in Homo erectus 1-2 million yrs old Ex: TB originated with emergence of Homo sapiens in Africa more than 70,000 yrs ago (know via DNA sequencing) We adapt and they evolve with us

Last Case of Smallpox (unnatural)

Jane Parker (1978)- British photographer, last recorded person in world to die from it Faulty ventilation system at Birmingham University Medical School; Janet worked on floor above lab where researchers experimenting with virulent isolated from Pakistani child; later Dr. Henry Bedson committed suicide while in quarantine (he shouldn't have been working with it since 1977 WHO rejected his application) Over 700 people immediately quarantined, Janet's mom got it but lived

Ingrafting

Make incision, rub (smallpox) powder into wound (popular in Europe, Great Britain, American colonies) All did it for protection (peasants and royalty)

do not

Many emerging diseases _____ move quickly (yet) Ex: some animal diseases not adapted for human hosts

Everywhere

Microbes are ____

Variola minor

Milder form of variola, *kills 1%*

Variola major

More serious form of variola, *mortality rate of 30%* Typically patients die of severe systemic illness (2nd week of symptoms)

Preventable Lower Respiratory, HIV/AIDS, diarrheal

Most of the leading causes of death are? Know the top leading causes of death (3) from the table worldwide

Genome

Poxviruses need a large ______ for viral DNA replication & gene transcription (to replicate in the cytoplasm)

Cytoplasm

Poxviruses unique among DNA viruses because they replicate *only* in the _____ of th host cell, outside the nucleus

Prevalence

Proportion of cases in the population at a given time *(total cases)* Used to determine level of morbidity

Smallpox rash

Rash progresses over 2 weeks -macules -papules -vesicles (blisters) -pustules -scabs -scars

Incidence

Rate of occurrence of *new* cases Conveys information about the risk of contracting a disease during a given time period

Mortality Rate

The number of deaths due to a disease divided by the total population