Michael H' Dong

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Toxicologic Side of Epidemiology (5th of 10
Lectures onToxicologic Epidemiology)
? readings

• Michael H. Dong
• MPH, DrPA, PhD

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

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• 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.

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

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• 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.

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• 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).

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• 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.

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

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• 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 1960-1961.
• Today it is used for leprosy treatment and as an
  immunosuppressant drug.

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• 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.

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• Thalidomide The Toxicologic Side
• Animal studies showed thalidomides
  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 chemicals structure.

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• 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.

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• 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.

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• 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.

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• 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).

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• AIDS/HIV The Toxicologic Side
• AIDS is caused by infection of HIV, which was
  identified in patients by Galo and Montagnier in
  1983-1984.
• The causal evidence satisfies essentially all
  Kochs 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.

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• 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.

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• 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.

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• 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.