Download Toxicology and Epidemiology (1st of 10 lectures on toxicological

Toxicologic Side of
Epidemiology
(5th of 10 Lectures on
Toxicologic Epidemiology)
Michael H. Dong

MPH, DrPA, PhD
readings
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 casedependent.
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
1960-1961.
•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 1983-1984.
•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.