Michael H. Dong MPH, DrPA, PhD  readings Toxicologic Side of Epidemiology (5th of 10 Lectures on Toxicologic Epidemiology)

Taken in the early ’90s, when desktop computers were still a luxury.

Learning Objectives Appreciate the importance of the toxicologic side of epidemiology. Study the toxicologic relevance through three historical epidemics. Learn the impact of toxicology, which is dynamic and case- dependent.

Performance Objectives Able to describe the epidemiologic course of the three historical events presented. To characterize the toxicologic side of these courses and events. To outline the purpose as well as the principles of presenting the three historical epidemics.

Three Case Studies for Toxicologic Side of Epidemiology: 1. Pellagra 2. Thalidomide 3. AIDS/HIV

Pellagra: History and Clinical Manifestations A nutritional disease caused by deficiency of niacin; in the old days related to poor corn diet. Clinical manifestations: dermatitis, diarrhea, dementia, and death. First reported in 1735, by a Spanish physician named Don Gaspar Casal.

Pellagra: The Epidemiology Recognized as a nutritional disease in 1913, when over 30,000 cases with a mortality rate of 40% already occurring in South Carolina alone. Socioeconomic prides prevented earlier Spanish from accepting the poverty reality; obsession with infectious disease in medical community also ignored a classic proof that pellagra is not contagious.

Pellagra: The Toxicologic Side Dietary studies in orphanages showed that the lack of a nutritional factor was responsible for the disease. Niacin as pellagra-preventative factor was identified in 1935, through the induction of black tongue in dogs (an animal disease having syndrome comparable to human pellagra).

Pellagra: The Impact of Toxicology That niacin is a pellagra-preventative factor is important to the prevention of pellagra. That nicotinic acid, nicotinamide, and tryptophan are biochemically related to one another also has a great impact on the prevention.

Pellagra: The Lesson Nutritional toxicology includes the effects of dietary deficiency. A disease like pellagra could be caused in part by political world’s resistance on accepting poverty as the culprit. It could also be caused by medical community’s obsession with infectious disease or other beliefs, until certain toxicologic facts become available.

Thalidomide: History and Manifestations It is a tranquilizer and a notorious human teratogen. It can cause fetal phocomelia and amelia if taken during pregnancy. Causal association was established in Today it is used for leprosy treatment and as an immunosuppressant drug.

Thalidomide: The Epidemiology The drug as the notorious human teratogen was implicated primarily by results of three epidemiologic studies. Two studies in Germany: Lenz and Knapp (1962); Weicher et al. (1962). One study in Australia: McBride (1963). All showed much higher incidence when taking thalidomide during pregnancy.

Thalidomide: The Toxicologic Side Animal studies showed thalidomide’s teratogenicity to be specific to species, to their tissues, and to time of exposure. These animal studies are critical not only for elucidation of mechanism of teratogenicity, but also because such toxicity could be related functionally to a chemical’s structure.

Thalidomide: The Impact of Toxicology Helping refine regulatory requirements for developmental testing. No longer treating genetic inheritance as a primary causal explanation for birth defects. Now tremendous increase in research on xenobiotic teratogens.

Thalidomide: The Lesson More stringent preclinical testing protocols are needed. Such protocols could have prevented the thalidomide tragedy and the like. Chemically-induced cases without characteristic appearance could escape attention, unless preclinical toxicity data are available to lend support.

AIDS/HIV: History and Clinical Manifestations Global epidemic of one of the most devastating of all diseases. AIDS is a medical condition in which the immune system suffers a progressive and often fatal failure; initially caused by HIV infection. Occurring as early as in 1950s in Africa, the first report of 31 AIDS-like cases was published in the USA in 1981.

AIDS/HIV: The Epidemiology Spread rapidly from a few cases in the USA in 1981, and now worldwide. As of 1997, the reported cases reached 1.7 million; of these, 50% were from Americas and 35% from Africa. The major route of HIV transmission involves sexual contact by homosexuals (60-65%), followed by needle sharing among drug users (25-30%).

AIDS/HIV: The Toxicologic Side AIDS is caused by infection of HIV, which was identified in patients by Galo and Montagnier in The causal evidence satisfies essentially all Koch’s postulates for identifying an infectious disease agent. Rapid self reproduction of HIV on the T4 white blood cells, but with a fatal slow effect on the immune system.

AIDS/HIV: The Impact of Toxicology Enlightens us about the long average (8 years) incubation of AIDS, or shorter by nutrition, stress; and about such toxic responses as weight loss, skin rashes, lack of resistance to infection, etc. Enables us to develop antiviral drugs to reduce the viral load, and drugs that can delay certain fatal opportunistic infections.

AIDS/HIV: The Lesson AIDS/HIV infection continues to rise worldwide and rapidly. The major route of HIV transmission is sexual contact with HIV-positive partners, followed by sharing needles among drug users. For cure and prevention, social choice apparently has opted to conducting more toxicologic research, rather than relying on changes in lifestyle.

Overview of Next Lecture Epidemiologic Side of Toxicology Through three toxicologic cases, to spotlight the importance as well as the relevance of epidemiology to toxicologic investigation. Also to reemphasize the somewhat arbitrary distinction between the two (toxicologic vs. epidemiologic) sides.