Transcript Syphilis - The NICU Peripheral Brain
N.Frewan, PL2 Neonatology Division July 2008
Congenital Syphilis
Background
Between 1905 -1910, Schaudinn & Hoffman identified cause of syphilis
T pallidum
as the The name "syphilis" was coined by Italian physician and poet Girolamo Fracastoro in his Latin written poem “Syphilis sive morbus gallicus” ("Syphilis or The French Disease") in 1530
Introduction
Curable STD caused by the Treponema pallidum organism 1998: Complete genetic sequence of
pallidum
was published which helped understanding the pathogenesis of syphilis Belongs to “Spirochaetaceae family” The genus name, thread “
Treponema,
is
T.
derived from the Greek term for "turning
Treponema Pallidum
Thin Motile Extremely fastidious Survive only briefly outside host Not cultivated successfully on artificial media
Transmission
Direct sexual contact with ulcerative lesions of skin or mucous membranes Trans placental: Typically during second half of pregnancy As early as 6 weeks of gestation Pregnant with primary or secondary syphilis are more likely to transmit the disease than those with latent (not clinically apparent) disease
Cannot be spread through contact with toilet seats, doorknobs, swimming pools, hot tubs, bathtubs, shared clothing, or eating utensils
Congenital syphilis
Severe, disabling, and often life threatening infection seen in infants About half of all infected fetuses die shortly before or after birth
Incidence US
Despite the fact of being curable if caught early, rising rates among pregnant ♀ in the US have recently ↑ the number of infants born with congenital syphilis
1985-1990: overall incidence ↑ 75% ( Sex-Drug traffic)
Incidence US
1998: 81.3% of reported cases of CS occurred because the mother received no/inadequate penicillin tx before or during pregnancy
According to the CDC: 40% of births are stillborn 40-70% of the survivors will be infected & 12% of these will subsequently die
Reported cases for infants < 1 year of age and rates of 1ry & 2ry syphilis among women: United States, 1997–2006
Rates for infants < 1 year of age: US, 1997–2006 and the Healthy People 2010 target as per STD surveillance
Incidence International
Worldwide, predominantly in large cities
Certain European countries have seen ↑in congenital syphilis cases
Major public health problem in sub Saharan Africa and developing world
Main focus in control: Antenatal screening & treatment of infected mothers
Jul-2006
Pathophysiology CS
Trans placental transmission Transmission rate:~ 60 - 100% With early onset disease, manifestations result from trans placental spirochetemia and are analogous to secondary stage of acquired syphilis CS does not have a primary stage
Clinical Manifestations
Intra-uterine: -Placenta -Fetus Post-natal: - Early - Late
Intra-uterine: Placenta
The placenta is typically large and edematous Characteristic placental findings include: - Hydrops placentalis Chronic villitis Perivillous fibrous proliferation Normoblastemia Necrotizing funisitis Acute chorioamnionitis Plasma cell deciduitis
Intra-uterine: Fetus
Depends on stage of development at time of infection & duration of untreated infection Initially characterized by placental involvement and hepatic dysfunction (e.g., abnormal LFT), followed by amniotic fluid infection, hematologic abnormalities, ascites, and hydrops Stillbirth / Neonatal death
Intra-uterine: Fetus
>24 weeks gestation: 66 % of fetuses have either congenital syphilis or T.Pallidum detected in amniotic fluid Intrauterine death: 25 % of affected Perinatal mortality: 25-30 %, if untreated
Post-Natal
Among survivors, manifestations been divided into: Early stage = First 2 years Late stage = After 2 years Inflammatory changes do not occur in the fetus until after first trimester → organogenesis is unaffected Nevertheless, all organ systems may be involved
Early CS- Asymptomatic
Occurs between 0 - 2 years If asymptomatic : - Identified on routine prenatal screening - If not identified and treated, these newborns develop poor feeding and rhinorrhea ➨ Earliest signs of CS may be poor feeding and snuffles (i.e., syphilitic rhinitis)
Symptomatic Early CS
If Symptomatic: Variable Appear within 1 st 5 weeks of life Stillborn/ Premature Failure to gain weight or FTT Fever / Irritability Severe congenital pneumonia
Symptomatic Early CS
Most striking lesions affect the mucocutaneous tissues and bones: - Mucous patches - Rhinitis =snuffle - Condylomatous lesions ➨ ➨ highly characteristic features of mucous membrane involvement in CS
Symptomatic Early CS
Snuffles → Followed quickly by diffuse maculopapular desquamative rash that involves extensive sloughing of the epithelium, on the palms & soles and around the mouth & anus When chronic → “Saddle Nose” Lesions & nasal fluid: highly infectious
Symptomatic Early CS
Bullous skin disease known as “pemphigus syphiliticus” ➲ Early rash -- small blisters on the palms and soles → Ulcerated ➲ Later rash -- copper-colored, flat or bumpy rash on the face, palms, and soles
Symptomatic Early CS
Other early manifestations include hepatosplenomegaly (100%), jaundice, anemia Metaphyseal dystrophy and periostitis often are noted on radiographs at birth +/_ Pseudoparalysis
Congenital syphilis - early evidence of infection - bullae and vesicular rash
Multiple, punched out, pale, blistered lesions, with associated desquamation of palms & plantars
Intraoral mucous patches & facial skin lesions
Secondary lesions on feet
Lesions first appeared during 4 th week
Late-onset CS
Develop from scarring related to early infection Can be prevented by treatment within first 3 months Can appear as late as 40 years after
Late-onset CS
Manifestations include neurosyphilis and involvement of teeth, bones, eyes, and 8th cranial nerve E.g.: Frontal bossing, short maxilla, high palatal arch, Hutchinson triad, saddle nose, and perioral fissure (Rhagades = bacterial infection of skin lesions )
Hutchinson triad
1.
2.
3.
Deafness (10 – 40 years) Hutchinson’s teeth = centrally notched, widely-spaced peg-shaped upper central incisors Interstitial Keratitis → blindness (5-20 years)
Notched incisors known as Hutchinson’s teeth
Moribund newborn with CS O ral / skin lesions and saddle nose
Metaphyseal osteomyelitis R adiolucent distal radius & ulna with cupping distal ulna
Osteochondritis of femur & tibia
1-m-old . Classical Wimberger's sign of destructive metaphysitis involving medial aspects of distal femora and proximal tibae
“Saber shins” = Osteoperiostitis Tibia
Interstitial keratitis
Possible Complications
Blindness Deafness Facial deformity Neurological problems
Labs
Definitive diagnosis: 1.
2.
By direct visualization of spirochetes using darkfield microscopy Or direct fluorescent antibody tests of lesion exudate or tissue (Placenta/UC) -Helpful early in the disease, prior to development of seroreactivity
Serologic tests
Presumptive diagnosis can be made using Nontreponemal ( False + in medical conditions) Treponemal (False+ in other spirochetal Diseases) → So use of only one type is insufficient - If nontreponemal test is +→ confirmatory testing is performed with a specific treponemal test
Nontreponemal test
VDRL (Venereal Disease Research Laboratory) RPR (Rapid plasma reagin) ART (Automated reagin test )
Nontreponemal test
Used for screening (sensitive but not specific) - Inexpensive, performed rapidly, and provide quantitative results → helpful indicators of disease activity & monitor treatment response Measures Ab directed against lipoidal Ag from T. Pallidum, Ab interaction with host tissues or both Nonspecific Ab develop 4-8 weeks following infection
Nontreponemal test
False negative Early primary S Latent acquired S Late CS
Prozone
phenomenon False Positive Viral infection ( EBV, Hepatitis, Varicela, Measles) Lymphoma TB Malaria Endocarditis CT diseases Pregnancy IV drugs Wharton Jelly contamination in cord samples
Nontreponemal test
Any reactive NT test must be confirmed by Treponemal test to exclude false positive Treatment should not be delayed if symptomatic or at high risk of infection Monitor: Sustained 4 fold ↓NT test titer after treatment → Adequate treatment - Sustained ↑: Re-infection or relapse
Nontreponemal test Newborn Dilemma
Testing of newborn often is problematic because IgG antibody may be a reflection of maternal rather than infant infection i.e.
Unless NT titer is much higher in baby than in mother → f/u serology over 1 required to make a diagnosis st 6 months of life, when maternal IgG is lost, would be Loosing precious time in treatment initiation
Treponemal Specific Test
T pallidum immobilization (TPI)
Fluorescent treponemal antibody absorption (FTA-ABS)
Microhemagglutination assay for antibodies to T pallidum (MHA-TP
)
Treponemal Specific Test
Confirm + nontreponemal reaginic test
Remain positive for life i.e. Result do not correlate with disease activity and tests are not quantified
False + reactions: → Other spirochetal diseases (e.g., yaws, pinta, leptospirosis, rat-bite fever, relapsing fever, Lyme disease
Cerebrospinal Fluid Analysis
CSF VDRL Could be negative and still develop signs of neurosyphilis →Therefore, all those with presumptive CS should be treated A nonquantitative VDRL test is the only serologic test that should be performed on CSF
Other test like FTA-ABS are less specific on CSF samples
CBC
CS characterized by anemia, thrombocytopenia, and either leukopenia or leukocytosis Evidence of Coombs-negative hemolytic anemia or a leukemoid reaction may be present
Imaging Studies
CXR: - Syphilitic pneumonia is common in CS - Fluffy diffuse infiltrate “pneumonia alba”
Imaging Studies
Long bone radiography – – – 95% of symptomatic infants and 20% of asymptomatic Multiple sites of osteochondritis at wrists, elbows, ankles and knees and periostitis of long bones The lower extremities almost always affected
Imaging Studies
Neuroradiography: Findings nonspecific May mimic herpes simplex virus MRI may reveal cerebral hypertrophy and hyperintensity in the temporal lobes
CDC Newborn Evaluation
The diagnosis of CS is complicated by the trans placental transfer of maternal nontreponemal and treponemal IgG Abs to fetus ➨ Making interpretation of reactive serologic tests for CS difficult
CDC Newborn Evaluation
Evaluation should include: 1.
2.
Maternal H/O syphilis including tx type & adequacy before and during the pregnancy P/E of newborn 3.
4.
5.
Quantitative NT & T tests CBC, long bone x-rays, CSF (VDRL, cell count, protein), and CXR and/or LFT Pathologic examination of placenta or umbilical cord using specific fluorescent antitreponemal antibody staining
CDC Newborn Evaluation
A presumptive diagnosis, which results in tx, is made if baby has + serologic test and any of following: 1.
Compatible findings on P/E 2.
3.
4.
5.
6.
CSF abn. (+ VDRL, ↑ WBC, or ↑protein) Osteitis on x-ray long bones Placentitis NT test 4x > than maternal Positive FTA-ABS-19S IgM antibody
Treatment
IV Penicillin G is the drug of choice for all stages of syphilis including CS Infants: - 100,000 - 150,000 U/kg/d IV Q12 x 7 d. then Q 8 to complete 10 days - Or Procaine Penicillin G 50,000 U/kg/d IM once for 10 days ( adequate CSF conc. may not be achieved)
Treatment
Indications: 1.
2.
3.
4.
If newborn meets any of criteria If mother was treated < 4 weeks prior to delivery If mother treated with other than penicillin If maternal titers suggest inadequate response to treatment before or early in pregnancy
Syphilis In Pregnancy
In communities in which risk for CS is high → serologic testing and a sexual history also should be obtained at 28 weeks gestation and at delivery Treat all pregnant patients with penicillin, regardless of the stage of pregnancy
Syphilis In Pregnancy
3 doses of benzathine penicillin (2.4 million U IM at 1-week intervals) No proven alternative treatment for patient allergic to penicillin i.e. Erythromycin for patient allergic to penicillin is not reliable treatment for fetus
Evaluation and Treatment of Infants During the First Month of Life
The following scenarios describe the evaluation and treatment of infants for congenital syphilis
Scenario 1 Infants with proven or highly probable disease and Abnormal P/E consistent with CS Serum quantitative NT titer 4x > mother’s titer or + darkfield or fl. ab. test of body fluids
Scenario 1 Infants with proven or highly probable disease and Recommended Evaluation Recommended Regimens CSF analysis for VDRL, cell count & protein CBC w. diff.& PL count Other tests as clinically indicated ( long-bone x rays, CXR, LFT, HUS, ophthalmologic exam, and BAER) Aqueous crystalline penicillin G 50,000 U/kg/dose IV Q 12 hrs. first 7 DOL and Q 8 hrs thereafter for a total of 10 days OR Procaine penicillin G 50,000 units/kg/dose IM in a single daily dose for 10 days
Scenario 2 Normal P/E & serum quantitive NT titer ≤ 4 x maternal titer Mother not / inadequately treated, or no documentation Mother was treated with erythromycin or other nonpenicillin regimen or Mother received treatment < 4 weeks before delivery
Scenario 2 Normal P/E & serum quantitive NT titer ≤ 4 x maternal titer Recommended Evaluation Recommended Regimens CSF analysis for VDRL, cell count, and protein CBC w. diff. and PLT count Long-bone X-rays Aqueous cryst. penicillin G 50,000 u./kg/dose IV Q 12 hrs during the 1st 7 DOL and Q 8 hrs thereafter for a total of 10 days OR Procaine penicillin G 50,000 units/kg/dose IM in a single daily dose for 10 days OR Benzathine penicillin G 50,000 units/kg/dose IM in a single dose
Scenario 3 Normal P/E & serum quantitive NT titer ≤ 4 x maternal titer Mother was treated during pregnancy, tx. was appropriate for the stage of infection, and treatment was administered > 4 weeks before delivery….. and Mother has no evidence of reinfection or relapse
Scenario 3 Normal P/E & serum quantitive NT titer ≤ 4 x maternal titer
Recommended Evaluation
⇩ No evaluation required
Recommended Regimen
⇩ Benzathine penicillin G 50,000 units/kg/dose IM in a single dose
Scenario 4 Normal P/E & serum quantitive NT titer ≤ 4 x maternal titer Mother’s treatment was adequate before pregnancy…. and Mother’s NT titer remained low and stable before, during pregnancy and at delivery (VDRL <1:2; RPR <1:4)
Scenario 4 Normal P/E & serum quantitive NT titer ≤ 4 x maternal titer
Recommended Evaluation
⇩
Recommended Regimen
⇩ No evaluation required No treatment required
Outlook (Prognosis)
Infected early in pregnancy ➨ stillborn Treatment of expectant mother ↓ risk of CS Babies who become infected when passing through birth canal have better outlook Death from CS is usually through pulmonary hemorrhage
References
www.cdc.gov/STD/STATS/figs.gif
Red Book (27 th edition)- 2006 Overview of TORCH infections: Karen E Johnson, MD. Uptodate 2006 Early congenital syphilis: Ameeta Singh, BMBS MSc,* Karen Sutherland, RN BScN,† Bonita Lee, MD MSc- pubmed Congenital syphilis re-emerging.
Simms I, Broutet N.