Download MI1-- : “Modern Plagues”

MI025 : “Modern Plagues”
Instructor: John Boothroyd, Ph.D.
Professor of Microbiology and Immunology
phone 723-7984
email: [email protected]
Summary.
In this “Freshman Seminar”, we will discuss the impact of modern plagues
on the world, a subject that could fill volumes. My goals for all students are
that by the end of the course you will:
-think critically; i.e., look at any health issue in the media critically and
think, “what are the data behind that...?”
-have an appreciation for the importance of infectious diseases in all aspects
of the world and especially from the view of humans.
-understand the factors that influence the emergence and, one hopes,
eventual control of a given disease.
-become an expert in one disease.
-improve your abilities to write and present effectively.
Logistics.
Enrollment is limited to 16 freshmen. The course will meet twice weekly for
about 1.5 hours per meeting. Each session will begin with a presentation on
a disease or set of diseases followed by a discussion based on assigned and
discovered readings. There is no exam for the course.
Readings.
There is a course reader and all are expected to have read the relevant
section before class to form the basis for discussion.
Book Report. [Due Tuesday, May 18]
Each student will select a book for reading and writing of a brief book
report (3 pages) addressing the strengths and weaknesses of the book.
Specifically, please:
1. Summarize the main thesis or theme of the book.
2. Give 6 quotes of hypotheses or conclusions, 3 of which are backed up by
solid data and sound logic and 3 of which are not (but the author does
not acknowledge this fact). Describe each in a brief paragraph and why
you assigned them to one or other of the two categories.
3. Would you recommend the book to your class-mates?
Oral Presentations.
Each student is expected to give an oral presentation and write one paper
(see below) on a “Modern Plague” other than the few I will discuss in the
first 7 weeks. I have listed possible topics in the syllabus but there are
plenty of others and I am flexible. If there is an infectious disease that
particularly catches your fancy, check with me but I will almost certainly
agree to adding that to the list. The presentations and papers must not be a
clinical description of a disease but should instead be a careful analysis of
the aspects that are behind the emergence of this disease as a “modern
plague”, and what might be the most effective control measures (and why).
ALSO, FIND WHAT IS UNIQUE TO YOUR DISEASE AND FOCUS ON
THAT POINT IN YOUR PAPER AND, ESPECIALLY, IN YOUR TALK –
WHAT’S THE “TAKE-HOME” LESSON/MESSAGE FOR THIS
DISEASE?
The oral presentations will be 20 minutes long and begin in the eighth week.
Practice sessions will be held with course assistants the week before your
presentation. The oral presentations can be in your own style but be sure to
BRIEFLY include the following information.
Disease:
1. Name of the disease and the causative agent (including
etymology).
2. Symptoms/Pathology.
3. Prevalence.
4. Pathogenesis. (What is responsible for the pathology)
5. Treatment.
Then discuss the historical background to the disease followed by a
discussion of two points you deem most interesting or most important. I
will add in my two cents worth at the end of your presentation.
I. What are the factors that have led to the current situation.
[you can use the list we compile as a way to think about this]
II. What are the possible control strategies and which should receive
the highest priority:
 avoidance (behavior, vectors, environment, sanitation, etc.)
 prophylaxis (vaccine, chemical)
 diagnosis
 treatment of symptoms
 cure infection
Exams. There will be no exam for this course.
Problem Sets: There will be one problem set. This will be short but should
help reinforce the concepts that emerge during our discussions. Group
discussion of the problems is allowed but you MUST answer them in your
OWN words.
Papers. The papers can be on the same subject as the oral presentation.
Again, please focus on the factors surrounding the emergence of the disease,
and only briefly describe the clinical symptoms.
I need three choices (ranked) by April 13. I will then allocate them based
on your rankings.
A one page proposal summarizing the material to be covered in the paper
is then due by 3:15 p.m., Tuesday, May 11 (email is fine). I will then
review these and make any comments as to possible changes in scope by
early May.
The papers should be organized as follows:
1. Summary of the main points (one page, maximum).
2. The biology of the infectious agent. (two pages, maximum)
3. The clinical picture associated with this disease. (two pages maximum)
4. The circumstances that have lead to the emergence of this disease. (eight
pages maximum)
5. What steps must be taken to effect control measures. (eight pages,
maximum)
6. Bibliography.
The papers must be typed, double spaced and should not exceed 15 pages,
excluding bibliography and figures. Some may wish to emphasize the
reasons behind the emergence of the disease while others may focus on
what’s to be done about it. Do not rely on only one or two sources and be
sure to search medline for recent information. Also, please be very careful
to acknowledge all quotes, citations and ideas! Where you think directly
quoting is important, use the following style:
As Miller put it, “The resurgence of malaria can be traced to a failure of
public health measures and indiscriminate use of insecticides and antimalarial drugs.” (1).
or
According to Miller, the return of malaria may be to a combination of
problems with public health measures and “indiscriminate use of
insecticides and anti-malarial drugs.” (1). Insert square brackets into quotes
where needed to restore context.
Lack of attribution is plagiarism and simple rephrasing does not make
the material original (i.e., it is still plagiarism if you take, “The resurgence
of malaria can be traced to a failure of public health measures and
indiscriminate use of insecticides and anti-malarial drugs.” and rephrase it
as, “The failure of public health meaures and indiscriminate use of
insecticides and anti-malarial drugs explains the resurgence of malaria.”
Be sure to be critical!!!!! Do you buy the argument
in articles you read???
Papers are due by the beginning of the last class; i.e., 3:15 p.m., June 3.
Severe penalties will occur for late papers!
Grades. Class participation (25%), book report (10%), the oral presentation
(25%), the problem sets (10%) and the paper (30%) will each count toward
the final grade.
Syllabus.
Microbiology and Immunology
“Modern Plagues”
Tuesdays and Thursdays 3:15-5:05
Class 1
Intro to course, microbiology, epidemiology.
discussion of student presentation topics.
Class 2
Smallpox eradication – why so successful?
Class 3
Joyce Moser – special seminar on effective written and oral communication.
Class 4
Choose books for book report.
Class 5
Polio - how to finish eradication.
Class 6
HIV – the importance of sex (not what you think).
Class 7
HIV - ethical issues of developing treatments for
developing countries.
Class 8
Influenza - how technology can respond.
Class 9
Helicobacter – microbes as causes of chronic disease.
Class 9
Malaria – up/down/up – resistance, DDT
Class 11
Malaria –the vaccine challenge and the nonlinearity between transmission and
disease.
Class 12
SARS – proportionate response for a fast emerger?
Class 13
Guest Lecture
Class 14
BSE/mad cow/vCJD - proportionate response for a slow emerger?
Class 15
Biological Warfare - a real risk??
Class 16
student presentations:
Sexually Transmitted
Hepatitis B, Hepatitis C, Kaposis Sarcoma Herpes Virus, Trichomonas, Herpes [Syphilis,
Gonnorhea]
Class 17
Student presentations
Sexually Transmitted (cont’d)
Class 18
student presentations:
Contact, Food or Water/Air Borne:
Rotavirus, Ebola, Hanta, Cholera, Hepatitis A, [Leprosy, Toxoplasmosis, Group A
streptococcus, Candidaisis, E. coli O157H, Shigellosis, Salmonella (various species),
Pneumocystis]
Class 19
student presentations:
Vector Borne:
Dengue, Lyme Disease, Sleeping Sickness, River Blindness [Typhus, Bubonic Plague,
Chagas’ Disease, Schistosomiasis, Leishmaniasis]
Class 20
student presentations
Vector Borne (cont’d)
Table 1. Classes of Infectious Agents.
Kingdom
Metazoa
Fungi
Protozoa
Bacteria
Viruses
Prions
Description
Multicellular
Hyphal and/or yeast forms; sexual
reproduction
Single celled eukaryotes, nonphotosynthetic
Single cells, no nucleus
Infectious agent that lacks most of the
components necessary for reproduction
Infectious agents that lack a genome
Examples
Worms
Candida
Malaria
Salmonella
Smallpox
Mad Cow Disease
Table 2. Infectious Agents to be Studied.
Kingdom
Metazoa
Class/Family
Cestoda
Tapeworms
Nematoda
Roundworms
Trematoda
Flatworms
Genus
Taenia
Species
solium
Disease
Cysticercosis
Onchocerca
volvulus
River Blindness
Schistosoma
mansoni
japonicum
Schistosomiasis/
Bilharzia
Fungi
Ascomycete
Deuteromycete
Pneumocystis
Candida
carinii
albicans
PCP(pneumonia)
Thrush/Candidiasis
Protozoa
Coccidia
Plasmodium
Malaria
Zoomastigophora
Toxoplasma
Trypanosoma
falciparum
vivax
ovale
malariae
gondii
brucei
cruzi
major
donovani
Yersinia
Vibrio
Streptococcus
pestis
cholerae
pyogenes
Mycobacteriu
m
Mycobacteriu
m
tuberculosis
Plague
Cholera
Flesh-eating Disease
Toxic-Shock-Like
Syndrome
Tuberculosis
leprae
Leprosy
Leishmania
Bacteria
Gram-Negative
Gram-Positive
Toxoplasmosis
Sleeping Sickness
Chagas Disease
Oriental Sore
Kala Azar
Viruses
Prions
Flaviviridae
Poxviridae
Flavivirus
Orthopoxvirus
Paramyxoviridae
Retroviridae
Orthomyxovirida
e
Picornaviridae
Filoviridae
Bunyaviridae
Morbillivirus
Lentivirus
Influenzavirus
Arenaviridae
Herpesviridae
Arenavirus
Cytomegalovir
us
Rotavirus
?
Reoviridae
?
Enterovirus
Hantavirus
Yellow Fever
Variola
Vaccinia
Rubeola
HIV
Influenzavirus
Yellow Jack
Smallpox
Cowpox
Measles
AIDS
Flu
Poliovirus
Ebolavirus
Sin Nombre
Virus
Lassa
Human CMV
Poliomyelitis
Ebola
Hantavirus
Pulmonary Syndrome
Lassa Fever
CMV retinitis
CMV inclusion
Diarrhea
Bovine Spongiform
Encephalitis/Mad
Cow Disease
Scrapie
Kuru; CreutzfeldJacob Disease
Group A
cow
sheep
human
Table 3. Microbiology Terms.
Term
MHC
Definition
Major histocompatibility complex: genes that were originally defined
based on ability to transplant tissue from one animal to another.
Eventually found to encode polymorphic proteins that present antigen to
the immune system.
Polymorphism Differences in gene or protein sequence that may or may not affect
phenotype.
Parasite
Pathogenesis
Sequelae
Virulence
what causes the pathology
phenomena that follow infection
disease severity.
A few Basics in Epidemiology.
Study of disease in GROUPS not individuals.
Statistics cannot be applied to individuals only groups.
Disease dependent on combination of four factors:
H
A
V
E
Table 4.
Epidemiology Terms:
Etiologic Agent
Etiologic Agent
Etiology
Herd Immunity
Iceberg Phenomenon
Mean
Median
Prevalence
Incidence
Range
Relative Risk
agent that causes a disease
causative agent
cause
immunization protects the unimmunized because transmission falls
below sustainable rate.
reported cases are fraction of actual number of cases which in turn is
a fraction of actual number of asymptomatic infections.
arithmetic average (2, 3, 4, 7, 9; mean = 5)
value that divides the group in half (4, in the above example)
number with a disease/total number in group at a given time
number who develop a disease in a given time frame/total number in
group at mid-point of the study.
lowest to highest value.
ratio of incidence in one group compared to another, usually of
lower susceptibility.
Resources.
Web sites:
1. Center for Disease Control in Atlanta (http://www.cdc.gov) has lost of
EXTREMELY useful sites. For example,
“Emerging Infectious Diseases” is a journal that is published in hard copy and is also
available on line. It is at http://www.cdc.gov/ncidod/eid.
“Morbidity and Mortality Weekly Report.” Presents a few short articles and full recent
statistics on all major U.S. health problems. This is a definitive, official publication that
is very up-to-date. The School of Medicine library also carries hard copies. The website includes a searchable index.
2. Scisearch is a website at Los Alamos National Laboratory that has essentially all
science articles indexed. It is accessible through:
http://bighorn.lanl.gov:6001/stanford/sciquery.html
3. WHO This has tons of information on disease of global importance. Great source of
recent facts and figures.
http://www.who.int
4. Pubmed (including Medline). Access to millions of articles in biology and medicine.
Citations usually include abstract but not remainder of the article.
http://www.ncbi.nlm.nih.gov/PubMed/
5. Lane Library (School of Medicine Library).
http://www.med.stanford.edu/lane/
Lots of useful sites including Socrates II. Stanford’s newest database of all library
collections.
http://sucat.stanford.edu/
6. ProMed. This is what the web is all about .... an exchange on a daily basis dealing
with whatever is deemed hot by “people out there”. The quality is uneven, sometimes
completely wrong, but a quick scan will reveal lots of interesting issues.
The following is what appears at the end of all ProMed listings and provides information
on how to subscribe.
“For all requests, send a message to: "[email protected]"
To (un)subscribe to the promed list, type: "(un)subscribe promed"
7. GAVI. Global Alliance for Vaccines and Immunization.
http://www.vaccinealliance.org/
This is a recently formed collective of private foundation (e.g. Gates, Rockefeller),
Governments, World Bank, WHO, etc. It has ambitious goals and, if it can meet the
bureaucratic challenges of such a diverse body, it could have a major impact on world
health.
8. American Society of Microbiology (ASM). This is a large organization with many
useful links to relevant sites. Their one on biowarfare/bioterrorism is most useful:
http://www.asmusa.org/pcsrc/bioprep.htm
Books:
Recommended:
Krause, R.M. 1998. Emerging Infections. Academic Press. New York. A tremendous
book with a great mix of scientific rigour and readability. Written by experts in the
respective diseases. If you can afford it, buy it!
Lederberg, J., Shope, R.E. and Oaks, S.C. (eds.) 1992. “Emerging Infections: Microbial
Threats to Health in the United States.” National Academy Press. Washington. [a “blue
ribbon” panel presents articles on “Factors in Emergence” and “addressing the Threats”.
Unlike most of the other books, this is written by practicing microbiologists.
Rhodes, R. “The Deadly Feast.” An extremely compelling book about prion diseases
starting with Kuru (a disease associated with cannibalism in Papua New Guinea) and
working through to the current debate on bovine spongiform encephalitis (“mad cow
disease”) and its possible link to human spongiform encephalitis, Creutzfeld Jacob
Disease. It is very readable and, although not written by a scientist, is rigorous and not
sensationalistic. Rhodes is a Pullitzer Prize winner for his previous book on the atomic
bomb.
McNeill, W. 1977. “Plagues and People.” Anchor Books, New York. As the
publication date might suggest, this book deals more with the historical plagues than the
modern variety. As such, it is an efficient way to delve into the historical context of the
most famous plagues and how they came to arise, be recognized and, in most cases,
conquered. It was one of the first serious look at the impact of plagues on human
development.
Garrett, L. 1995. “The Coming Plague.” Virago Press, London.
Wills, C. 1997. "Yellow Fever, Black Goddess." Their origin, history and future.
Flamingo Press, London. This is a very up-to-date and far less gloomy discussion of
many modern plagues with a distinct trend toward population biology. A superb
paperback though I need to check its availability in the U.S.
Oldstone, M.B.A. 1998. "Viruses, Plagues and History." An excellent and very readable
discussion of Lassa, Yellow Fever, Measles, Polio, Ebola, Hantavirus, HIV, BSE and Flu.
A very good starting source book.
Diamond, J. 1997. "Guns, Germs and Steel." An extremely interesting discussion of how
guns, germs and steel (and horses!) have affected development of different societies in the
old and new worlds.
Ewald, P. 2000. "Plague Time : How Stealth Infections Are Causing Cancers, Heart
Disease, and Other Deadly Ailments". An interesting discussion of the role of infection
in causing chronic disease. Also, see "Evolution of Infectious Disease" (1994) which
presents some interesting ideas about how virulence and transmission are balanced.
Alibek, K. 1999. “Biohazard” Random House, NY. An in-depth description of the
Soviet biological warfare program by someone high-up in that program.
Worth a Look...
Karlen, A. 1995. Man and Microbes: Diseases and Plagues in History and Modern
Times. Touchstone Press, New York. A well written book that is thoroughly researched
and covering a wide range of infectious diseases. It moves from one to the other in
thematic ways and is not sensationalistically written.
Isada, C., Kasten, B., Goldman, M., Gray, L. and Aberg, J. 1996. Infectious Disease
Hanbook. 2nd Edition.. Lexi-comp Inc., Hudson Ohio. This is a no-nonsense reference
book for the physician but an excellent, compact reference for keeping near to hand as
one embarks on any reading. It presents the facts, nothing but the facts, on all aspects of
infectious diseases from symptoms to the organisms, treatments, vaccines, etc.
Desowitz, R. 1977. “Who Gave Pinta to the Santa Maria.” Norton & Co. New York.
McCormick, J. and Fischer-Hoch, S. 1996. “Level 4: Virus Hunters of the CDC.”
Turner Publishing, Atlanta.
Biddle, W. 1995. “A Field Guide to Germs.” Henry Holt & Co. New York. A short
guide to all the germs you will hear about in this course with a page or two on each that
gives the key aspects in a conversational style. Eclectic in its choice of what to tell, it is a
very easy, quick reference.
Ryan, F. 1993. “The Forgotten Plague.” Little, Brown & Co. Boston. Subtitled, “How
the Battle Against Tuberculosis Was Won and Lost.”, this book is a thorough discussion
of the battle to control TB, initial successes and its recent resurgence.
Nikiforuk, A. 1991. “Fourth Horseman - A short history of epidemics, plagues, famines
and other scourges.” Evans & Co. New York. A discussion of factors that influence
several famous diseases through the millenia.
Curtin, P. D. 1989. “Death by Migration- Europe’s encounter with the tropical world in
the nineteenth century” Cambridge University Press, Cambridge. Quantitative study of
the relocation costs among European soldiers in the tropics. Part of the book discusses
what Europeans at the time thought the causes of death among the soldiers were and how
it ultimately influenced the practice of medicine.
Leavitt, J. 1996. “Typhoid Mary- captive to the public’s health” Beacon Press, Boston.
Interesting look at the case of Mary Mallon AKA “typhoid Mary” and the tensions
between personal liberties and public safety.
Ryan, F. 1997. “Virus X-tracking the new killer plagues out of the present and into the
future.” Little, Brown and co. Boston.
Shilts, R. 1987. “And The Band Played On” St. Martin’s press, NY. Historical analysis
of how the political, medical and social institutions influenced the spread of the AIDS
epidemics.
Rothman, S. 1994. “Living in the Shadow of Death- Tuberculosis and the Social
Experience of Illness in American History” Basic Books, NY.
(and lots more!)
Textbooks:
Friedman, G. 1994. “Primer of Epidemiology.” 4th Edition. McGraw-Hill Inc., New
York. Just what the name says, this is a short text-book that teaches the essentials of
epidemiology. It has more than most might want but for checking essentials of how casecontrol studies are really done (or should be done), it provides an excellent introduction.
Jekel, J., Elmore, J. and Katz, D. 1996. “Epidemiology, Biostatistics and Preventive
Medicine.” W.B. Saunders Co., Philadelphia. A textbook of intermediate length and
detail. Concise but useful guide for the newcomer.
Brooks, G., Butel, J. and Ornston, N. 1995. “Jawetz, Melnick and Adelberg’s Medical
Microbiology. 20th Edition.”. Appleton and Lange, Norwalk, Connecticut. A classic that
is a serious but approachable textbook in infectious diseases for use as a more complete
resource on this subject than the Infectious Disease Handbook. Includes chapters on
microbial metabolism, cultivation, microbial genetics and immunology as well as the full
spectrum of diseases discussed here.
....plus many others in Lane and Falconer Libraries!