Syphilis (Lecture 3) – Tuskegee Study

(Updated 12 February 2006)

NOTE: These notes cover the material for two lectures (syphilis 2 and syphilis 3).

The diesase and the Epidemiology

The Spirochetes

  • Treponema pallidum causes Syphilis
  • Another Treponema causes Yaws
  • Another Spirochete (Borelia burgdorferi) causes “Lyme Disease”
  • Good tests for Treponema, no good test for Borelia

Syphilis is an STD (STI)

  • “Sexually transmitted” and “venereal” both used
  • Infection is preferable to disease
  • Can also be transmitted by blood contact
  • Can also be transmitted by direct contact with open chancres
  • CANNOT be transmitted by toilet seats, drinking cups, doorknobs, money, etc.

Syphilis has three stages

  • Primary — mild and goes away
  • Secondary — mild and goes away
  • Tertiary — often latent for many years
    • does not go away
    • often does irreversible damage
  • (Lyme Disease also has three stages)

Primary Syphilis

  • chancre
    • hard red nodule
    • ulcerates
    • filled with infectious Treponema pallidum bacteria
    • usually painless
  • starts 10-90 days after exposure, lasts 1-5 weeks

Secondary Syphilis

  • symptoms throughout the body
  • malaise and fever
  • rashes of various sorts
  • swollen lymph glands and small swellings on mucous membrane
  • starts 0-10 weeks after chancre, lasts 2-6 weeks
  • highly infectious

Latent Syphilis

  • no symptoms but bacteria still there and growing
    • heart, eyes, nerved, bones, joints, liver, brain
  • usually relatively non-infectious
  • eventually damage so serious that symptoms occur
  • often fatal
  • usually starts an autoimmune response

Tertiary Syphilis

  • Many forms, depending on which organs are affected
  • Neurological and cardiac are among the most common
  • Almost any tissue can be the target
  • Really, it is just which one fails first

Congenital Syphilis

  • bacterial cross the placenta
  • stillbirth if pregnancy occurs during primary or secondary syphilis
  • if pregnancy occurs during latent syphilis
  • about 40% of infected newborns go to “fulminating” disease
  • about 60% go into latency and symptoms occur later

Diagnostic methods

Older

  • very unreliable, too many different symptoms
  • lots of underreporting to protect reputations

Newer

  • Wasserman test 1906
  • Specific antibodies

Wasserman Test

  • Complement Fixation
  • Quick and easy
  • Not ENTIRELY reliable
  • Now replaced by a direct antibody assay

Complement Fixation

  • If an antibody binds to an antigen
    • a conformational change happens
    • a molecule called “complement” binds to the complex
    • complement tries to punch a hole in whatever the antibody is attached to
  • If the antibody is attached to cells, they lyse
  • If to a small molecule, the complement is “wasted”

The Wasserman Test

  • Mix human serum (blood minus cells) with cardiolipin and complement
    • If there are antibodies in the blood, the complement is used up by the complex
    • If not, there is still free complement
  • Add sheep cells coated with antibody
    • If there is still complement left, they lyse
    • If all is used up, they don’t lyse.
  • In other words:
    • If there is anti-syphilis antibody (anti-cardiolipin antibody), it binds to cardiolipin and then complement binds and removed from the mixture
    • If there is no anti-cardiolipin antibody, the complement won’t bind in the first mixture and is still there when the sheep cells are added.

Why Complement “Fixation”

  • “Fixed” means permanently attached to something.
  • The complement is “fixed” to the anti-syphilis (anti-cardiolipin) antibody
  • Opposite of fixed is free
  • If free complement when coated (activated) blood cells are added, lysis follows

Modern tests

  • Monoclonal antibodies and fluorescence
  • PCR

Treatments for Syphilis

  • Mercury rubs since the 1500’s
    • “One night with Venus, the rest of your life with Mercury”
  • Salvarsan (Arsphenamine), an arsenic compound 1910
  • And a less toxic form, neosalvarsan
  • Requires multiple injections and careful monitoring of the dosages

“Dr. Erlich’s Magic Bullet” (Paul Erlich)

  • Magic Bullets
    • First “specific” curative chemical and foundation of all later chemotherapy, including antibiotics
  • Age of optimism
    • Triumph of bacteriology (Koch, Pasteur, Yersin, – same era)
    • Remember the other diseases???
    • Methylene Blue and malaria!

Modern Treatment for Syphilis

  • single dose of penicillin for active, multiple doses for latent
  • almost 100% effective
  • no resistance yet seen — a real puzzle!
  • Contact notification and public health laws
  • problems with late stage treatment
  • autoimmune responses

Prevalence of Venereal Disease

Prevalence of Syphilis

  • Prevalence of Venereal Disease in General
  • probably 30% of the men
  • often higher in war time
  • effect on family
    • “venereum insontium” — innocent syphilis or gonorrhea

Prevalence of Syphilis 1880-1920

  • estimates are imprecise
  • perhaps 10% of the population of the US
  • Best numbers come from military

Prevalence of Syphilis (recent)

  • Effects of social attitudes on syphilis trends
  • not always obvious
  • note that cure (penicillin) does not mean eradication
  • gonorrhea is usually about 10-20 times higher

Current trends in Syphilis rates

Social Attitudes and Syphilis

Victorian times (1880-1910) and World War I

  • Role of Family changes to child rearing
  • Double standard
    • men are naturally sexual and aggressive, women are pure and keepers of the home
    • women best kept ignorant of sex until husbands teach them
    • too pure and weak
    • too dangerous and sinful
  • falling birthrate

STDs as a threat

  • Gonorrhea
    • single birth sterility
    • falling birthrate among white middle class
    • silver nitrate for the eyes
  • syphilis
    • innocent infections of newborns

Syphilis as a threat

  • race purity and eugenics
    • America was the home of modern eugenics
    • not very fashionable after the Nazis
  • syphilis as “dirty”
    • prostitutes
    • African Americans
    • immigrants

Eugenics in America?

Medical Confidentiality

  • can’t tell wife where syphilis came from
  • must tell lies or allow misapprehensions
  • story of the drinking cup

Medical attitude toward syphilis

  • many refuled to treat syphilitics
    • too morally disreputable for a refined practice
    • no much money in it
  • easier after the “discovery” of innocent infections

Physicians vs. Public Health Departments

  • question of turf
  • fear of state medicine
  • question of morals
    • public health depts. tended to be pragmatic
    • but even this was in tension
  • IHSB (Interdepartmental social hygiene board) within PHS by act of Congress 1918

The 1920’s and 30’s

  • AMA objections to ISHB and prophylaxis
  • Obscenity laws and Religious objections
  • Abandonment of anti-venereal funding for public health
  • The rise of Thomas Parran, one of the nations greatest syphilographers

Social Hygiene movement

  • Part of general Progressive movement
  • Two conflicting elements
    • moralists
    • pragmatists

Tensions within Social Hygiene movement

  • WCTU and the Catholic Church forbade discussion of condoms and even discouraged education about cures
  • Public health workers argued that sex education and condoms were necessary because education had failed

Medical objections

  • general conservatism
  • objection to state medicine
    • testing required laboratories (maybe acceptable)
    • treatment required injection (relatively new in the early years but then more common)
    • if public health clinics gave injections, how would doctors earn a living?

Education and Morality

  • always part of the American scene
  • Double standard forbade mention of syphilis
    • 1934: CBS Radio forbade the NY State Health commissioner from mentioning “syphilis” or “gonorrhea” because of obscenity laws
    • similar state laws banned the educational films from W.W.I
  • Increased efforts led to no noticeable effect

Role of the Media

  • Plays: “Damaged Goods” (1913)
  • Ladies’ Home Journal
    • series of articles on VD in 1906 cost them 75,000 subscribers
    • broke the barrier in 1937
  • Time and leading newspapers started in 1936
  • Always a problem with censorship

World War I

  • experience from Mexican action against Pancho Villa warned about venereal disease
  • Wasserman test made it clear that it was there
  • Social Hygiene movement had two horns
    • moralistic educators
    • medical and public health proponents

The European Army Approach

  • Inspection of Prostitutes and issuance of licenses
    • But inspection cannot tell, often no symptoms
  • Tolerance of men’s “needs”
    • Actually welcomed licensed brothels to the camp areas
  • American soldiers who came under European systems achieved the same high infection rates as English and French.

American Army approach

  • Abstinence from prostitutes
    • predecessor of USO type activities
  • provision of prophylactics (latex condoms)
  • provision of post-coital prophylaxis
  • criminalization of syphilis
    • court martial offense
    • moral equivalent of desertion

Prophylaxis

  • condoms: effective against syphilis and gonorrhea
  • post-coital treatments
    • wash
    • mercuric chloride (bichloride of mercury)
    • protargol for 5 minutes (a silver containing protein mixture)
    • mercurous chloride (calomel)
    • waxed paper and wait 4-5 hours

Effectiveness of prophylaxis

  • only 3.4% of soldiers developed a venereal infection
    • vs. about 10% with syphilis alone at home!!
    • most syphilis in the army came in from draftees
  • probably well over 90% effective
  • the moralists battle against prophylaxis was ineffective during the war
  • about 10 fold lower rates than other European armies

After the War (The good news)

  • Effective treatment (Salvarsan)
  • Progressive Movement
  • Thomas Parran
  • Success of the pragmatic approach in Social Hygiene

After the War (The bad news)

  • Medical objections to public health TREATMENT
  • Re-emergence of moral views suppressed by wartime fears (or patriotism)
  • Government retrenchment after the War
  • The great depression

1920-1946

  • Lots of public health growth
  • Lots of tension and conflict
  • Common belief that syphilis must be eradicated
    • by moral education
    • by public health measures
  • Real question of WHETHER it was possible

An age of experimentation

  • contact notification
  • pre-marital testing
    • in Michigan it is a felony for a syphilitic to marry
  • how to reach infected segments of the populaiotn
    • homeless, poor, prostitutes, the very rich, the immigrants, etc.

The Tuskeegee study

“The Tuskeegee Study of Untreated Syphilis in the Negro Male”

The Timeline of the story

  • Noble beginnings
  • pragmatic compromise
  • “crimes against humanity”

Noble Beginnings

  • Despite racist beliefs, public health movement was learning
  • Disease germs are the most democratic creatures in the world
  • Disease is often the same in all races

Disease is the same?

  • Not always
    • Many West Africans are relatively resistant to the American strain of malaria
    • Lots of slave census numbers say some resistance to yellow fever and other tropical fevers
  • But TB and syphilis “might” be related to poverty more than race

(Implication of differences in disease resistance

  • Planters said: Africans are more resistant to tropical disease so it is “natural” that they should be the ones enslaved to till the land here — Europeans all die off when enslaved here.
  • Alexis deTocqueville said: Africans seem well adapted to this place, so Europeans should go home and leave the Africans to colonize this place.)

Syphilophobia

  • High percentage of Wasserman positive found in World War I recruits scared all
  • Enormously high % among rural blacks
  • Racist views of cause, but
  • Need to cure blacks or risk the whites.

Mississippi demonstration project

  • Can rural black population be treated?
  • Funding from govt. limited
  • Role of the Rosenwald foundation
  • lots of work for southern blacks
  • long tradition of govt/foundation cooperation

Treatment regime:

  • 25 injections of neosalvorsan plus 200 mercury rubs over a i-year course
  • Would they come?
  • Would the planters send them?
  • YES!

Expansion

  • Success of Mississippi led to broader project
  • 20 new counties across the South
  • Funding from govt. much reduced due to postwar conservatism
  • Rosenwald foundation broke rules and allowed “continued bunding”
  • Rockefeller foundation joined
  • Just started and then it collapsed

The crash

  • government funding dies with the depression
  • Rosenwald foundation goes broke
  • Rockefeller foundation almsot broke
  • But all the statistics in place:
  • Macon county Alabama is the poorest

The Salvage attempt

  • If can’t afford to treat, at least can collect the data
  • Role of Tuskeegee Institute
    • Needed goodwill of government
    • Guaranteed respectability among blacks

The “criminal conversion”

  • Originally “untreated” was because of lack of money
  • The study made it a goal!

The Tuskeegee Study

Warnings:

  • Do not judge history by any moral standards except its own
  • Nevertheless, there is much to judge here

Enrollment of Local Population

  • Church and School used to recruit
  • Treatment for “Bad Blood” promised
  • Free burial insurance ($50) — a BIG draw
  • Used the “already started” population from the demonstration project
    • 339 with and 201 without syphilis

Tuskeegee Institute

  • Premier Black center of higher learning
  • Medical Schhool, Hospital, Nursing school
  • Dependent on Federal (and local) govt. for goodwill and money
  • Involved, but not in charge

Local contact

  • Nurse: Eunice Rivers
    • Recommended by Tuskeegee
  • Maternal control: She was a nurse!
    • Power base

Annual “roundup”

  • Medical exam
  • Aspirin, lunch, and iron tonic as “treatment”
  • Men actually did feel better!
  • Doctors came from Washington
    • Mostly just statistical collection of symptoms

Denial of Treatment

  • Draftees late in World War II
  • All syphilitics treated with neosalvarsan (then penicillin) and then inducted
  • Miss Rivers tracked them down and got them exempted from service
  • Even got them out of the hospitals!
  • Local doctors who saw the men were disciplined by local med. Association

Judgements

  • Medically flawed
    • many had been treated before the study began (“untreated?”)
    • many moved from control to experimental after the study began
  • Informed consent?
    • Men told they were treated for Bad Blood
    • Tests and placebos were called “treatments”

“Follow to autopsy” — withholding of treatment

  • some arguments for withholding salvorsan and mercury
    • but those are not valid
  • no justification for withholding penecillin
    • but that was not different than the salvorsan argument

After Nürnberg Laws

  • Nazi concentration camps and medical experimentation
  • Prime issue, informed consent
  • Nobody cared

The Study continued until 1972

  • Ongoing study published openly at regular intervals
  • Many public health officers rose to the top in the VD service
  • No budget, so where else to make a name?
  • Parran then Clark then Vonderlehr
  • Local health depts involved as men moved out of Macon county

The End of the Study

  • Peter Buxton (an interviewer for the study) as “whistleblower”
  • Not readily believed 1966-1972
  • Jean Heller (AP reported) broke the story in NY Times in 1972
  • Edward Kennedy started hearings and quickly ended the thing

Complexity of the issues

  • The PHS
  • Tuskeegee
  • Nurse Rivers
  • The men
  • The times

Is it over?

  • AIDS in Africa and Asia