History and Epidemiology of
Syphilis
Nigar Kirmani, MD
Associate Professor
Washington University School of Medicine
St. Louis, MO
Syphilis
Systemic infectious condition caused by
Treponema pallidum
A sexually transmitted disease, but not
exclusively sexually transmitted
A major public health threat
– financial impact of patient management
– financial impact of partner notification
– cost of congenital disease
History of Syphilis
Paleopathology shows that syphilis was
present in New World prior 1492
Probably introduced into Europe after 1492
Pustular syphilis: “Great Pox”
Tremendous long-term consequences
– neurological impairment
– bone, skin, cardiovascular involvement
History of Syphilis
Troops of French King Charles VII were
severely afflicted after seige of Naples in
1495
Seen in paintings and woodcuttings of late
1490’s
Bethencourt first used term “lues venerea”
in 1527
History of Syphilis
First description of
syphilis, ca. 1495
History of Syphilis
Syphilis in Europe
Syphilis named after hero of 1530 poem by
Fracastoro of Verona (“Syphilis sive
Morbus Gallicus”)
Gonorrhea and syphilis were thought to be
the same disease, or variations of each
other, for the next 300 years
– frequent association of GC with syphliis
– urethral discharge due to urethral chancre
Monist Theory of Syphilis
John Hunter’s experiment -- 1767
– inoculated self with exudate of patient with
gonorrhea
– Hunter contracted syphilis (but patient was co-
infected with both diseases)
– site of exudate contact believed to cause
disease form
» gonorrhea in mucous membranes
» syphilis on the cutaneous surfaces
Syphilis Treatment
Over the years, a variety of treatments have
been employed for syphilis
Few therapies enjoyed much success until
the advent of penicillin in the mid-20th
century
Syphilis Treatment - Guaiacum Wood
Ironwood from
Lignum vitae tree
West Indies and S.
America
Great pharmaceutical
marketing in its day
– But drug was
worthless for syphilis
Syphilis Treatment - Malariotherapy
Julius Ritter Wagner von Juaregg
Syphilis Treatment – Heat Therapy
Kettering Heat Box
Arsenicals
Compound “606” – The Magic Bullet
– Arsphenamine (Salvarsan) discovered 1909
– “Relatively” nontoxic
– Other arsenicals followed
Very cumbersome and lengthy treatment
schedules
Need to alternate with other heavy metals
(bismuth, mercury)
Arsenicals
Serious adverse consequences (including
death) were not uncommon with arsenical
therapy
WW II accelerated treatment schedules
tried
– Rapid treatment centers
– 300,000 draftees treated and accepted into
military service
Rapid treatment center
World War II
Penicillin
1943 – Mahoney et al. discovered the anti-
treponemal activity of penicillin
By 1944, clinical trials throughout the U.S.
showed penicillin’s promise
How did we come to standardize penicillin
therapy for syphilis?
Syphilis -- “The Great Imitator”
Phrase coined by Olser more than 100
years ago.
However, the phrase continues to ring
true in the HIV era, since syphilis can
resemble a number of other medical
conditions
Epidemiology of Syphilis in U.S.
Spirochetal infection
– 6 microns long, 0.15 microns wide
– Slow replication in vivo
Peak infection 1945
– 600,000 total cases reported
Minor epidemic peaks every 10-12 years
Transmission
Sexual transmission (90% of cases)
Prenatal/perinatal/congenital
Rare:
– transfusion-associated
– accidental inoculation in laboratory
Syphilis — Reported cases by stage of
infection: United States, 1941–2005
Cases (in thousands)
600
P&S
Early Latent
480 Total Syphilis
360
240
120
0
1941 46 51 56 61 66 71 76 81 86 91 96 2001
Primary and secondary syphilis — Rates
by region: U.S., 1996–2005and the
Healthy People 2010 target
Rate (per 100,000 population)
10
West
Midwest
8 Northeast
South
2010 Target
6
4
2
0
1996 97 98 99 2000 01 02 03 04 05
Note: The Healthy People 2010 target for P&S syphilis is 0.2 case per 100,000
population.
Primary and secondary syphilis — Rates by
state: U.S. and outlying areas, 2005
2.5
VT 0.2
0.8 0.2 0.1 NH 1.2
1.1 1.4
MA 1.9
1.4 0.7 3.7
RI 2.2
0.3
0.0 1.0
CT 1.7
0.3
NJ 1.5
1.6
4.7 0.2 DE 1.3
1.8
0.4 4.1 1.0 MD 5.6
4.4 1.0 0.2 1.9
0.7 2.6 1.3
Guam 1.2
3.7
3.2 Rate per 100,000
3.0 1.2 population
2.9 1.9 2.0
3.7 7.3
1.7 4.0 (n= 8)
Puerto Rico 5.8
Virgin Is. 0.9
Note: The total rate of P&S syphilis for the United States and outlying areas
(Guam, Puerto Rico and Virgin Islands) was 3.0 per 100,000 population. The
Healthy People 2010 target is 0.2 case per 100,000 population.
Primary and secondary syphilis —
Rates by county: United States, 2005
Rate per 100,000
population
4.0 (n= 195)
Note: The Healthy People 2010 target for P&S syphilis is 0.2 case per 100,000
population. In 2005, 2,434 (77.5%) of 3,140 counties in the U.S. reported no
cases of P&S syphilis.
Primary and secondary syphilis — Cases
by reporting source and sex: U. S., 1996–
2005
Cases (in thousands)
5
non-STD Clinic Male
non-STD Clinic Female
STD Clinic Male
4 STD Clinic Female
3
2
1
0
1996 97 98 99 2000 01 02 03 04 05
Primary and secondary syphilis — Rates by
race/ethnicity: U.S., 1996–2005
Rate (per 100,000 population)
40
White
Black
32 Hispanic
Asian/Pac Isl
Am Ind/AK Nat
24
16
8
0
1996 97 98 99 2000 01 02 03 04 05
Primary and secondary syphilis — Age-
specific rates among women 15 to 44 years
of age: U.S., 1996–2005
Rate (per 100,000 population)
15
15-19
20-24
25-29
12 30-34
35-39
40-44
9
6
3
0
1996 97 98 99 2000 01 02 03 04 05
Primary and secondary syphilis — Age-
specific rates among men 15 to 44 years of
age: U.S., 1996–2005
Rate (per 100,000 population)
15
15-19
20-24
25-29
12 30-34
35-39
40-44
9
6
3
0
1996 97 98 99 2000 01 02 03 04 05
Syphilis — Reported cases by stage of illness:
United States, 1941–2004
Cases (in thousands)
600
P&S
Early Latent
480 Total Syphilis
360
240
120
0
1941 46 51 56 61 66 71 76 81 86 91 96 2001
Gender distribution
Between 1981-1997, rates among men and
women converged
– 1981 male / female ratio > 3 : 1
– 1999 male / female ratio = 1 : 1
Since 1997, increasing male-female
divergence
– 2001: male / female ratio > 2 : 1
– 2004: male / female ratio > 6 : 1
Primary and secondary syphilis — Rates:
Total and by sex: U. S. 1986–2005 and the
Healthy People 2010 target
Rate (per 100,000 population)
25
Male
Female
20 Total
2010 Target
15
10
5
0
1986 88 90 92 94 96 98 2000 02 04
Note: The Healthy People 2010 target for P&S syphilis is 0.2 case per 100,000
population.
Primary and secondary syphilis — Male-
to-female rate ratios: U.S., 1996–2005
Male-Female rate ratio
10:1
8:1
6:1
4:1
2:1
0
1996 97 98 99 2000 01 02 03 04 05
Age distribution
Males tend to be somewhat older than
females
– Male median age 30s
– Female median age 20s
Primary and secondary syphilis — Age-
and sex-specific rates: U.S., 2005
Men Rate (per 100,000 population) Women
15 12 9 6 3 0 Age 0 3 6 9 12 15
0.0 10-14 0.1
2.4 15-19 1.9
8.1 20-24 3.0
10.1 25-29 2.1
11.4 30-34 1.5
13.2 35-39 1.7
10.9 40-44 1.4
5.3 45-54 0.5
2.0 55-64 0.1
0.4 65+ 0.0
5.1 Total 0.9
Congenital syphilis
Infected at birth
Rates have fallen steadily since 1991
Congenital syphilis — Reported cases for
infants <1 year of age and rates of primary
and secondary syphilis among women: U.S.,
1996–2005
CS cases (in thousands) P&S rate (per 100,000 women)
1.6 4
1.2 P&S Syphilis 3
0.8 2
0.4 1
0.0 0
1996 97 98 99 2000 01 02 03 04 05
Congenital syphilis — Rates for infants <1 year
of age: United States, 1996–2005 and the Healthy
People 2010 target
Rate (per 100,000 live births)
50
Congenital Syphilis
2010 Target
40
30
20
10
0
1996 97 98 99 2000 01 02 03 04 05
Note: The Healthy People 2010 target for congenital syphilis is 1.0 case per 100,000 live
births.
Local epidemiology of syphilis
In 2003:
– St. Louis ranked 23rd among all US cities for
primary and secondary syphilis
In 2004:
– St. Louis ranked 5th among all US cities for
primary and secondary syphilis
19 counties and independent cities account
for 50% of all syphilis in the US
Will we get there ???
How do we get there ?