EPIDEMIOLOGY 606

Advanced Infectious Disease Epidemiology

Tuesdays, Thursdays 1:30-3:00 P.M. Rm 3040 SPH I

INSTRUCTORS

	Steve Meshnick	Jim Koopman
Office	2039a SPH I	3043 SPH I
Phone/e-mail	7-2406, meshnick@umich.edu	3-5629, jkoopman@umich.edu
Office hours	Tuesdays 3-5	Tuesdays and Thursdays, 5-6 in SPH-II, computer lab

COURSE DESCRIPTION

This second course in epidemiology will further prepare students to practice infectious disease epidemiology in health departments, NGOs, and academic settings. It addresses the processes and mechanisms which make infectious disease epidemiology differ from non-infectious disease epidemiology with regard to risk assessment and control program implementation. Focus will be on how risk factors, contact patterns, transmission dynamics, and pathogen evolution determine endemic and epidemic levels of infection. This in turn will serve as a basis upon which to discuss how a) vaccination, b) hygiene and sanitation, c) vector control, d) alteration of contact patterns, and e) treatment programs should be organized to minimize endemic and epidemic infection levels.

COURSE OBJECTIVES

This course will provide a theoretical framework for understanding the causes of endemic and epidemic infection patterns in terms of a) the biology of infection, b) risk factors for transmission, c) transmission dynamics, and d) evolution dynamics.
It will provide a practical framework for organizing and evaluating infection control efforts that balance and coordinate the contributions made by a) vaccination, b) hygiene and sanitation, c) vector control, d) alteration of contact patterns, and e) treatment.
Diverse infectious diseases of public health importance will be explored to illustrate these principles of theory and practice.

COMPETENCIES

Students will be prepared to qualitatively assess the effects on endemic and epidemic infection levels of a) risk factor frequencies, b) risk factor distributions to different population segments, c) patterns of immunity in the population, d) contact patterns, and e) temporal changes in a) through d). They will be taught to recognize what is needed for quantitative assessment of these effects but they will not learn how to actually perform such assessments.
Students will develop criteria to decide upon public health actions involving the following decisions: 1) which initial investigations of possible infection clusters or outbreaks should be carried out to maximize the chance of discovering controllable causes of disease, 2) how to design and conduct the investigations to best inform decisions about infection control activities, 3) how to choose and implement control activities, 4) how to allocate resources efficiently to different types of control activities, 5) how to monitor the effectiveness of control activities in a manner that lends itself to continuous quality improvement, 6) how to involve the community and Public agencies outside of Public Health in efforts to control infections.
Students will understand the biological, environmental, social and political factors that underlie control of diseases via: a) sanitation and hygiene measures, b) immunization, c) altering infection transmitting contact patterns, d) vector control, e) treatment that can eliminate contagiousness in infected individuals.

READINGS AND SOFTWARE

Required readings will either be on the Web or on reserve in the SPH library. In addition, students are expected to purchase copies of Stella software ($65 for Mac or PC).

GRADING

Midterm 30%

Presentation 30%

Final 40%

CLASS PRESENTATIONS

Students will work in small groups and then give oral presentations in class at the end of the semester. The presentations should focus on specific disease entities or types and take an integrative approach which applies the principles presented in the course. Two weeks before the presentation, students should present a list of readings for other students to read on the topic before it is presented. They should also present a list of questions or topics that will be discussed in their presentation. Suggested topics include but are not confined to:

Biological warfare
Rotavirus
Zoonoses such as Lyme disease
AIDS
Otitis Media and vaccines
Opportunistic pathogens such as P. carinii or CMV.
Pneumonia.
Transmissable Spongiform Encephalopathies
Nosocomial infections such as Coagulase Negative S. aureus or Enterococci.

The presentations should include:

Descriptive epidemiology	Geographical distribution, risk factors, impact, surveillance and control
Biological issues	Natural history of infection, pathogen factors (virulence, diversity), host factors (immunity, genetics), infection detection methods
Transmission systems	Mode of transmission, R(o) estimates, important variables in the transmission system and how they affect dynamics, effect of asymptomatic infections and carriers, how different the transmission system is between developed and developing countries and how that might affect control.
Open questions	What else needs to be known/investigated?

SYLLABUS

Date	Instructor	Lecture Title	Topics
9/8	Meshnick	History and Overview	Infectious diseases and history Changing paradigms of disease
9/10	Koopman	Transmission Systems: General concepts and need for Transmission System Analysis (TSA)	The nature of infectious agent transmission systems. How to learn TSA TSA assumptions in standard epidemiological analyses The non-linear nature of infectious disease dynamics The role of TSA in policy decisions, predicting infection levels, advancing scientific theory, understanding how infection is disseminated, identifying currently ignored causes of infection, identifying inconsistencies in what we think we know, specifying the most important investigations, and designing the most efficient studies.
9/15	Meshnick	Host response to infection	Introduction to immunology Genetics of susceptibility
9/17	Koopman	Transmission system classes and R(0)	The elements of TSA Population subgroups Contact processes Agents and their variants Transmission processes Infection processes Immunity processes Birth-death processes
9/22	Meshnick	Biological characteristics of infectious agents and their implications for transmission, disease and control	Evolution of virulence Lifecycles, reservoirs and routes of transmission Prions Macroparasites Oncogenic viruses (HHV-8)
9/24	Koopman	Modeling generic transmission systems that require further elaboration to make them specific to mode of transmission.	Analysis of simple SIR models with and without birth-death processes
9/29	Meshnick	BREADTH DAY lecture on International Health
10/1	Koopman	Risk factor effects	Subdividing populations by exposure status and analyzing exposure effects
10/6	Meshnick	Vaccines and drugs for infectious disease	Vaccines Antibiotics & antiparasitics; Evolution of drug resistance Single vs multiple drug therapy Social marketing

10/8	Koopman	Modeling control programs		Parameter changes corresponding to sanitation, behavior change, and treatment.
10/13		MIDTERM
10/15	Meshnick	Water- and food-borne infections		General Hepatitis Helicobacter Cryptosporidia
10/20	Koopman	Vaccine effect models		All or none and partial susceptibility effects How vaccine effect estimates must be interpreted Vaccine effects on the course of infection
10/22	Meshnick	AIDS and other STDs		Natural history of infection Control programs in developed and developing world Cofactors for HIV infection and pathogenesis
10/27	Koopman	AIDS/STD models		Formulating contact more explicitly Contact patterns as the dominant determinant of level of infection in populations.
10/29	Meshnick	Mycobacterial diseases		TB pathogenesis: history; changes in transmission patterns Leprosy Control strategies
11/3	Koopman	Modeling Rx as a control program		When treatment can control transmission Modeling antibiotic resistance
11/5	Koopman	R(0) measurement		Homogeneous contact theory of R(0) determining rate of epidemic rise endemic infection level and average age of infection Heterogeneous contact and R(0)
11/10	Meshnick	Mosquito-borne diseases		Malaria and dengue Immunity and disease severity Control programs
11/12	Meshnick	Helminths		Hookworm (history and current unknowns) Guinea Worm Eradication Program Schistosomiasis. Onchocerciasis (OCP and APOC)
11/17	Koopman	Agent Diversity (Malaria and Gonorrhea)		The distortions that arise from failing to distinguish strains that do not strongly cross react Using molecular diversity of agents for analyzing transmission systems
11/19	Students
11/24	Students
12/1	Students
12/3	Students
12/8	Students
12/10	Meshnick-Koopman		Summary and Review for Final

MESHNICK LECTURE READING ASSIGNMENTS

Date	Lecture Title	References
9/8	History and overview	Tomes, chaps. 1, 4 and 5.
9/15	Host response	Nagel, Singh, Bellamy
9/22	Biological characteristics	Bundy, Ewald, Levin, Moore & Chang, Pattison, Webber, chaps. 1 and 2 http://www.who.int/emc/diseases/bse/
9/29	BREADTH DAY
10/6	Water- and food-borne infections	Alterkruse, Black, Guerrant, Marshall http://www.who.int/emc/diseases/hepatiti/ http://www.mediconsult.com/frames/peptic/shareware/focus/index.html
10/15	Vaccines and drugs	Meshnick, Montaner http://www.who.int/gpv-dvacc/ http://foundation.novartis.com/socintro.htm
10/22	AIDS and other STDs	http://www.who.int/emc-hiv/global_report/index.html http://www.who.int/asd/docs.htm
10/29	Mycobacterial diseases	China TB, Colditz, Tomes, N. chaps. 2-3; Webber sect. 13.8 http://foundation.novartis.com/ leprosy.htm http://www.who.int/lep/ http://www.who.int/gtb/
11/10	Mosquito-borne diseases	Snow and commentary,Trigg, Whittle http://www.who.int/ctd/ http://micscape.simplenet.com/mag/art98/aedrol.html
11/12	Helminths	Stoltzfus http://www.who.int/ctd/ http://www.who.int/ocp/

Reading list (on reserve in SPH library or on Web)

Alterkruse, S. EID 3:285, 1997 (http://www.cdc.gov/ncidod/EID/vol3no3/cohen.htm)

Bellamy, R. NEJM 338:640, 1998.

Black, R. Vaccine 11:100,1993.

Bundy, D. 1992. W.H.O. Stat. Q. 45:168-179.

China Tuberculosis Control Collaboration. Lancet 347:358, 1996.

Colditz, G. JAMA 271:698, 1994.

Ewald, P. EID 2:245, 1996 (http://www.cdc.gov/ncidod/EID/vol2no4/ewald.htm)

Guerrant, R. EID 3:51, 1997 (http://www.cdc.gov/ncidod/EID/vol3no1/guerrant.htm)

Levin, B. EID 2:93, 1996 (http://www.cdc.gov/ncidod/EID/vol2no2/levin.htm)

Marshall, B. 1995. JAMA 274:1064-1066.

Meshnick, S.R. in Malaria: Parasite Biology, Pathogenesis and Protection. ASM Press, 1998, p. 341

Montaner, J. Drug Res. Updates 1:157, 1998.

Moore, P.S. and Chang, Y. Am.J.Epid. 147:217, 1998.

Nagel, R. Blood Cells 16:321, 1990.

Pattison, EID 4:390, 1998 (http://www.cdc.gov/ncidod/EID/vol4no3/pattison.htm)

Singh, N. EID 3:41, 1997 (http://www.cdc.gov/ncidod/EID/vol3no1/singh.htm)

Snow, R. Lancet 349:1650, 1997. Commentary 350:362-364, 1997.

Stoltzfus, R. Nutrition Rev. 55:223, 1997.

Tomes, N. The Gospel of Germs. Harvard University Press, Cambridge, 1998.

Trigg, P., and Kondrachine, A. 1998. Bull. W.H.O. 76:11-16.

Webber, R. Communicable Disease Epidemiology and Control. CAB International.

Whittle, H., and Boele van Hemsbroek, M. Malaria. In Health and Disease in Developing Countries, Macmillan, 1994.