MI025 : “Modern Plagues”

Instructor: John Boothroyd, Ph.D.

Professor of Microbiology and Immunology

phone 723-7984

email:

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 anti-malarial 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 / Description / Examples
Metazoa / Multicellular / Worms
Fungi / Hyphal and/or yeast forms; sexual reproduction / Candida
Protozoa / Single celled eukaryotes, non-photosynthetic / Malaria
Bacteria / Single cells, no nucleus / Salmonella
Viruses / Infectious agent that lacks most of the components necessary for reproduction / Smallpox
Prions / Infectious agents that lack a genome / Mad Cow Disease

Table 2. Infectious Agents to be Studied.

Kingdom / Class/Family / Genus / Species / Disease
Metazoa / Cestoda
Tapeworms / Taenia / solium / Cysticercosis
Nematoda
Roundworms / Onchocerca / volvulus / River Blindness
Trematoda
Flatworms / Schistosoma / mansoni
japonicum / Schistosomiasis/
Bilharzia
Fungi / Ascomycete / Pneumocystis / carinii / PCP(pneumonia)
Deuteromycete / Candida / albicans / Thrush/Candidiasis
Protozoa / Coccidia / Plasmodium / falciparum
vivax
ovale
malariae / Malaria
Toxoplasma / gondii / Toxoplasmosis
Zoomastigophora / Trypanosoma / brucei
cruzi / Sleeping Sickness
Chagas Disease
Leishmania / major
donovani / Oriental Sore
Kala Azar
Bacteria / Gram-Negative / Yersinia / pestis / Plague
Vibrio / cholerae / Cholera
Gram-Positive / Streptococcus / pyogenes / Flesh-eating Disease
Toxic-Shock-Like Syndrome
Mycobacterium / tuberculosis / Tuberculosis
Mycobacterium / leprae / Leprosy
Viruses / Flaviviridae / Flavivirus / Yellow Fever / Yellow Jack
Poxviridae / Orthopoxvirus / Variola / Smallpox
Vaccinia / Cowpox
Paramyxoviridae / Morbillivirus / Rubeola / Measles
Retroviridae / Lentivirus / HIV / AIDS
Orthomyxoviridae / Influenzavirus / Influenzavirus / Flu
Picornaviridae / Enterovirus / Poliovirus / Poliomyelitis
Filoviridae / Ebolavirus / Ebola
Bunyaviridae / Hantavirus / Sin Nombre Virus / Hantavirus Pulmonary Syndrome
Arenaviridae / Arenavirus / Lassa / Lassa Fever
Herpesviridae / Cytomegalovirus / Human CMV / CMV retinitis
CMV inclusion
Reoviridae / Rotavirus / Group A / Diarrhea
Prions / ? / ? / cow
sheep
human / Bovine Spongiform Encephalitis/Mad Cow Disease
Scrapie
Kuru; Creutzfeld-Jacob Disease

Table 3. Microbiology Terms.

Term / Definition
MHC / 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 / what causes the pathology
Sequelae / phenomena that follow infection
Virulence / 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 / agent that causes a disease
Etiologic Agent / causative agent
Etiology / cause
Herd Immunity / immunization protects the unimmunized because transmission falls below sustainable rate.
Iceberg Phenomenon / reported cases are fraction of actual number of cases which in turn is a fraction of actual number of asymptomatic infections.
Mean / arithmetic average (2, 3, 4, 7, 9; mean = 5)
Median / value that divides the group in half (4, in the above example)
Prevalence / number with a disease/total number in group at a given time
Incidence / number who develop a disease in a given time frame/total number in group at mid-point of the study.
Range / lowest to highest value.
Relative Risk / 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 web-site 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: ""

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.