(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