Syphilis – A Review Barbara Romanowski MD, FRCPC Clinical Professor Faculty of Medicine & Dentistry University of Alberta September 16, 2008 Association Between Genital Ulcers
• Any genital ulceration is associated with an increased risk of HIV acquisition and transmission
• HIV can be cultured from lesion exudate
• Therefore, HIV serology for all patients with genital ulcers and vice versa Reported Infectious Syphilis Rates in Alberta and Canada, 1994 to 2007 Note: National rates for 2006 and 2007 are preliminary. Source: Surveillance and Epidemiology Section, Centre for Communicable Disease and Infection Control, Public Health Agency of Canada 2008; http://www.phac-aspc.gc.ca/std-mts/stdcases casmts/index.html) and Alberta Health and Wellness Communicable Disease Reporting System: Notifiable Diseases and Sexually Transmitted Infections Databases as of June 11, 2008 Infectious and Congenital Syphilis Cases in Alberta 2007 (n=255)
* 4 of the 7 symptomatic CNS cases were ocular
Source: Alberta Health and Wellness Communicable Disease Reporting System: Notifiable Diseases and Sexually Transmitted Infections Databases as of June 11, 2008
Gender-Specific Age Distribution of Infectious Syphilis Cases in Alberta, 2007 Age (yrs)
Source: Alberta Health and Wellness Communicable Disease Reporting System: Notifiable Diseases and Sexually Transmitted Infections Databases as of June 11, 2008
Male Infectious Syphilis Cases in Alberta by Sexual Preference, 2003-2007
Source: Alberta Health and Wellness Communicable Disease Reporting System: Notifiable Diseases and Sexually Transmitted Infections Databases as of June 11, 2008
Infectious Syphilis – HIV Status in Regions 3 and 6, Alberta, 2007 Calgary Health (Region 3) Capital Health (Region 6) n=100 cases n=106 cases Unknown, Unknown, 16, Positive, 9, Positive, 24, 24% Negative, Negative, 81, Note: In 2007, there was one HIV positive infectious syphilis case outside of Capital and Calgary Health Region.
Source: Alberta Health and Wellness Communicable Disease Reporting System: Notifiable Diseases and Sexually Transmitted Infections Databases as of June 11, 2008
Sexual Contact 3-4 weeks Infectious Primary Syphilis 6-8 weeks Secondary Syphilis lymphadenopathy Latent Syphilis Early <2 years Late > 2 years Spontaneous Cure Tertiary Static positive serology Primary Syphilis Incubation 9-90 days (average
• Chancre
• Regional lymphadenopathy Secondary Syphilis
• Mucocutaneous eruption
• Generalized lymphadenopathy
• Constitutional symptoms Latent Syphilis
• asymptomatic • positive serology < 2 years – early latent infectious 25% relapse to secondary > 2 years – late latent non-infectious Tertiary Syphilis
• 3-30 years after primary infection
• Non-infectious
• Types late benign – skin, bone, viscera Cardiovascular – aorta, heart Neurosyphilis – meninges, brain Outcome of Pregnancy in Relation to Stage of Untreated Maternal Syphilis Primary or Late Normal Secondary Prematurity Perinatal death Congenital syphilis Healthy child Congenital Syphilis Early < 2 years of age Late > 2 years of age
• mucocutaneous &
• interstitial keratitis bony lesions
• mulberry molars
• hepatosplenomegaly
• Hutchinson’s teeth
• meningitis
• saddle nose
• perforation of hard Summary of Congenital Syphilis Cases, Alberta, 2005 to 2007
• All 14 cases were born in Edmonton to 13 mothers (1 set of twins)
• 5 neonatal deaths
• Ethnicity: 8 First Nations, 4 Caucasian, 1 Asian
• Marital status: 6 married/common-law
• 5 sex trade workers
• 8 mothers did not access antenatal care and were not tested for syphilis until delivery; 1 mother was tested in the second trimester but could not be located and the remaining 4 tested negative for syphilis early in pregnancy Source: Communicable Disease Reporting System: Notifiable Diseases and Sexually Transmitted Infections Databases as of June 11, 2008 Diagnosis of Syphilis 1. History 2. Physical Examination 3. Laboratory Investigations A) Darkfield examination / DFA B) Serology Serologic Tests for Syphilis
• Non-treponemal test
RPR VDRL ART EIA RST
• Treponemal test
MHA-TP / TP-PA FTA-Abs Serologic Tests for Syphilis
• EIA – treponema specific test – detects
• improved sensitivity / specificity
• has replaced RPR, TPPA, FTA-Abs
• cannot differentiate venereal from non- venereal treponemal infection i.e. yaws / pinta INNO-LIA®
• measures antibodies to T pallidum antigens
• will remain positive for life
• will be only run initially to confirm EIA Interpretation of Syphilis EIA
• EIA -ve - no syphilis or incubating. Consider repeating in 2 – 4 weeks
• EIA +ve - syphilis. RPR will be done to determine titres
• EIA +ve / RPR –ve / LIA +ve – syphilis False Positive Reactions NON-TREPONEMAL TREPONEMAL
• viral infections
• autoimmune
• pregnancy
• malaria
• genital herpes
• leprosy
• elderly
• pinta
• injection drug abuse
• cirrhosis
• autoimmune Indications for CSF Examination
• any neurological abnormalities • before re-treatment of patients who have had a relapse
• in all infants • in the investigation of patients with late latent syphilis and an RPR ≥ 16 Diagnosis of Congenital Syphilis
• physical examination
• serology
if maternal transfer – titre should gradually decrease & disappear by 6-12 months.
if congenital infection – titre will increase
• CSF examination
• long bone x-rays Treatment of Syphilis “A night on Venus, but a month on Mercury” Primary, secondary, early latent
• Benzathine penicillin 2.4 mu IM STAT
• Doxycycline 100 mg bid x 14 days Latent > 1 year duration
• Benzathine penicillin 2.4 mu IM weekly for 3 successive weeks
• Doxycycline 100 mg bid x 28 days Treatment of Syphilis in Pregnancy
• All women not previously treated should receive penicillin appropriate to their stage of disease
• Some experts suggest that pregnant women with early syphilis received 4.8 mu benzathine penicillin
• Retreatment during pregnancy is unnecessary unless there is clinical or serologic evidence of new infection
• When penicillin allergy is reported, desensitization should be attempted Syphilis Screening during Pregnancy
• All pregnant women should have syphilis serology undertaken at their 1st pre-natal visit
• Serology should be repeated at 28 – 32 weeks gestation
• For “high-risk’ women serology should again be repeated at term Congenital Syphilis Neonates should be treated at birth if: • They demonstrate symptoms/signs of congenital syphilis
• Maternal treatment was inadequate
• Maternal treatment is unknown
• Maternal treatment was with drugs other than penicillin RPR Titre Decrease After Treatment of Infectious Syphilis PRIMARY 2 tube decrease at 6 months 3 and 4 tube decrease at 12 and 24 months SECONDARY 3 and 4 tube decrease at 6 and 12 months EARLY LATENT 2 tube decrease at 12 months Source: Romanowski B. Annals Int Med 1991;114:1005
China’s Hisun Files IND For Cholesterol-lowering Drug In U.S. Hisun, best known for a proposed JV with Pfizer on branded generics, is looking to move up the value chain into R&D. SHANGHAI – One of China’s leading active pharma-latory consulting for the IND preparation (CMC, phar-ceutical ingredient and finished product manufacturers macology/toxicology and clinical development plan/
The Association for British Clinical Diabetologists: recommendations following suspension of rosiglitazone (Avandia) On 23 September 2010, the European Medicine’sAgency (EMA) Committee on Medicinal Products forHuman Use (CHMP) recommended the suspension ofmarketing authorisation for Avandia (rosiglitazone)• For all new prescriptions of thiazolidinediones, and Avandamet (rosiglitazone
Syphilis – A Review
Infectious Syphilis – HIV Status in Regions 3 and 6, Alberta, 2007
Secondary Syphilis
Outcome of Pregnancy in Relation to 
Diagnosis of Syphilis
INNO-LIA®
Indications for CSF Examination
Treatment of Syphilis in Pregnancy
RPR Titre Decrease After Treatment of