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THERE IS SOMETHING
LURKING OUTSIDE YOUR
BACK DOOR
Amanda O’Neil, MSN, CNP
Sanford USD Medical Center Sioux Falls, SD
AND…..
IT IS NOT WHAT
YOU THINK
OBJECTIVES
Objective 1:
Discuss presentation of congenital syphilis
1. Identify signs and symptoms of congenital syphilis
2. Identify medical management of congenital syphilis
3. Identify follow up care for congenital syphilis
Objective 2:
Describe syphilis
1. Recognize the incidence of syphilis
2. Categorize primary, secondary, early, and late syphilis
3. Increase awareness of appropriate diagnostic tools and treatment
MATERNAL HISTORY
• 27 year old
• G8P6
• Late prenatal care @ 28 weeks
• c/o abdominal pain & intermittent bleeding
• RPR positive @ 28 weeks; left AMA & Untreated
• Gestational diabetes, Polyhydraminos, Cigarette Smoker
• Presented 31 3/7 with bleeding, abdominal pain, BPP 4/8
• Stat c-section for breech & abruption noted
DELIVERY
Apgars 2-6-7
• Outlying facility
• Umbilical cord tore
• PPV, chest compressions
x 1 minute
• Transport team arrived at
20 minutes of age
TRANSPORT EVENTS
Metabolic Acidosis
Respiratory Distress
Anemic
Thrombocytopenic
Clinical Findings
Hepatosplenomegaly
Hypoglycemia
Vesicular bullous lesions on
hands & feet
TRANSPORT EVENTS
2.0 L nasal cannula
UAC/UVC D10W @ 80 ml/kg/day
D10W 2 ml/kg bolus x 2 & Normal Saline 10 ml/kg x2
Blood culture, CBC, Ampicillin and Gentamicin
Vitamin K & Erythromycin
ADMISSION
PHYSICAL EXAM
Respiratory distress, intercostal retractions, grunting, FiO2 increasing to 75%
Distended abdomen
liver edge 3.5 cm below costal margin, spleen 2 cm below costal margin
Color gray, mottled, scattered petechia, purpura
Vesicular bullous lesions on hands and feet
PHYSICAL EXAM
INITIAL RESULTS
4 Hours Old
• Blood gas 7.19/54/34/-7/21
• Blood sugars 29-50; Insulin & cortisol normal
• DIC Screen delayed Protime & INR
• Initial CBC: WBC 4,300; Hct 29.4%, Platelets 5,000,
Neutrophils 10%, Band 9%, Metamyeloctyes 2%; I:T
0.52; ANC 817
INITIAL X-RAY
INITIAL MEDICAL
MANAGEMENT
Respiratory
FEN
Heme
ID
• Increased Conventional Ventilator Settings
• Curosurf x 1
• Increased GIR
• 2 ml/kg D10 bolus x 2
• Platelets, PRBCS, & FFP
• Added Acyclovir
• Sent viral studies
CONTINUED COURSE
RESPIRATORY
First 24 hours
Arterial Blood Gases
• pH 7.22-7.34
• PCO2 44-52
• PO2 63-100
• Base Deficit (-8)- (-1)
• CO2 Content 21-25
CONTINUED COURSE
FEN/GI/GU
Hours of Age
12
24
30
Sodium
Potassium
Chloride
CO2
BUN
Creatinine
Calcium
Ionized Calcium
Bilirubin Total
Bilirubin Direct
Alkaline Phosph
ALT – SGPT
AST – SGOT
Protein Total
Albumin
Blood sugars
130 (L)
4.0
100
20 (L)
14
0.80
7.5 (L)
128 (L)
3.5
96 (L)
25
19
0.93
7.0 (L)
1.05 (L)
8.2
127 (L)
3.6
94 (L)
25
21 (H)
0.86
7.3 (L)
6.3
0.3
255
42
144 (H)
4.7 (L)
2.2 (L)
63-116
175
58
247 (H)
4.8 (L)
2.2 (L)
9.3
1.7 (H)
CONTINUED COURSE
FEN
Total fluids at 100 ml/kg/day
D16 with a GIR 9.7 to maintain euglycemia
Urine output decreasing, foley catheter, lasix x 2, Bumex
DAY OF LIFE 1
DAY OF LIFE 1
CONTINUED COURSE
GI/GU
• 1 spotlight of phototherapy started at 4
hours of age for a T bili of 3.8
• 2nd spotlight added at 12 hours of 6.8
• Direct bilirubin from 0.3-1.7 in 24 hours
• Cholestasis TPN, limit 1g/kg of intralipids
• Abdominal ultrasound: liver enlargement & ascites
CONTINUED COURSE
HEME/ID
• WBC 7.2
• Hgb 11.2
24 hours of Life
• Hct 33
• CRP 178
• Platelets 35,000
• Anemia
• ANC 4104
• Segs 30
• Bands 27
• Metas 4
• I:T 0.51
• 4 PRBC infusions
• Persistent
Thrombocytopenia
• 5 transfusions of
platelets
CONTINUED COURSE
ID
RPR Reactive; Titer 1:16 (Mom titer 1:32)
Obtain CSF when stable
Continued Amp, Gent, Acylovir
Cultures & HIV/HSV pending
CONTINUED COURSE
ID
Urine CMV negative
Consulted ophthalmology
Normal head ultrasound
LONG BONE
RADIOGRAPHS
LONG BONE
RADIOGRAPHS
CLINICAL
MANIFESTATIONS OF
CONGENITAL SYPHILIS
CLINICAL MANIFESTATIONS
Early <2 years old
Snuffles
Rash on hands & feet
Fever
Bone changes
Hepatosplenomegaly
Petechiae
Jaundice
Pneumonia
Osteochondritis
Pseudo paralysis
Hemolytic anemia
Leukocytosis
Thrombocytopenia
IUGR
CNS Involvement
CLINICAL MANIFESTATIONS
EARLY
Hepatosplenomegaly
• Present in nearly all cases
• 33% have jaundice secondary to hepatitis or
hemolytic processes
• May have elevated D. bili, Indirect bili,
elevated alk phos
• Sometimes LFTs worsen with Pen G treatment
CLINICAL MANIFESTATIONS
EARLY
Hematologic Manifestations
• Coombs negative hemolytic anemia
• May progress to chronic non hemolytic anemia
• Thrombocytopenia
• Decreased platelet survival
• May be only manifestation
• Hydrops fetalis
CLINICAL MANIFESTATIONS
EARLY
Mucocutaneous Manifestations
• Rhinitis/Snuffles
• Early feature, mucous-like discharge (highly infectious)
• Cutaneous Lesions
• Maculopapular eruption (oval, pink, changes to coppery
brown)
• Pemphigus syphiliticus (vesiculobullous eruption on
palms & soles)
CLINICAL MANIFESTATIONS
EARLY
Bone Lesions
• Most frequently encountered
• Osteochondritis, osteomyelitis, & periostitis
• Nonspecific & variable metaphyseal changes
• Pseduoparalysis of Parrot (↓movement & ↑pain)
• Wimbergers Sign (mataphyseal defects on the
upper medial aspect of the tibia)
WIMBERGER’S SIGN
BACK TO THE CASE
CONTINUED COURSE
DAY 2
Respiratory
FEN
GI/GU
• Oxygen needs decreased
• Weaning on ventilator
• Significant weight gain
• 2nd dose of Bumex
• TF 100 ml/kg/day
• Direct Bilirubin 2.9
• AST decreasing
• Creatinine & BUN
increasing
Heme
• Received plts x 4
ID
• I:T 0.77
• Too unstable to obtain
CSF
CONTINUED COURSE
DAY 3
Stable on ventilator
Received 3 Platelet transfusions
Direct bilirubin rising (3.5)
Urine output increased significantly, hypernatremia
Increased total fluids 120 ml/kg/day
CONTINUED COURSE
DAY 3
Sent specific Treponemal Antibody Test
Obtained CSF- cell count, protein, & VDRL
HIV, HSV, Urine CMV Negative
Blood culture no growth
Gram stain & Culture of foot lesion no growth
CONTINUED COURSE
DAY 3
Discontinued
Amp, Gent,
Acylovir
Started
Penicillin G
Total
treatment
of 10 days
CSF RESULTS
RBC CSF Cell Count
1095 (H)
WBC CSF Cell Count
28 (H)
% Neutrophils CSF
20 (H)
% Lymphocytes CSF
59 (H)
% Large Mononuclear CSF
20 (L)
% Eosinophil CSF
1 (H)
Glucose CSF
43 (L)
Protein CSF
292.8 (H)
VDRL CSF
Positive 1:2 (A)
CSF Culture
No growth
NEUROSYPHILIS
Penicillin G
treatment for 14
days
Follow up with
pediatric infectious
disease at 3
months of age
ADDITIONAL FINDINGS
Eye exam normal
Treponema Pallidum Antibody Test Reactive
Extubated at 12 days of age
Received 21 Platelet transfusions
DISCHARGE
Discharged at 41 4/7 weeks CGA (71 days in NICU)
Currently taking Prevacid, Multivitamin, Albuterol, & Miralax
Infant has an Apnea Monitor
At 4 months of age RPR was non reactive
At 4 months of age skeletal survey unremarkable
DISCHARGE
Post discharge pt. had influenza
Diagnosed with intermittent exotropia (unrelated to
congenital syphilis)
Admitted inpatient for pneumonia
at 4 months of age for 6 days
At 6 months of age will need repeat CSF including VDRL
CONGENITAL SYPHILIS
FOLLOW UP CARE
Regular well child visits: 2, 4, 6, 12
months
Serological NTA every 2-3 months until
non reactive or titer decreases 4 fold
(1:16 to 1:4)
Neurosyphilis
• CSF examinations at 6 month intervals until normal
• If abnormal, consider retreatment
• MRI
WHAT IS SYPHILLIS?
A sexually acquired
infection caused by the
bacteria treponema
pallidum
• Thin motile spirochete
• Subspecies can cause
bejel, pinta, & yaws
INCIDENCE OF SYPHILIS
• Most recent data in United States 10.1 cases of congenital
syphilis per 100,000 live births
• Increased 23% between 2003-2008
• 2012: 322 reported congenital syphilis
• 2013: 350 reported cases
• For the first time in 50 years, in 2013 the southern region
of the U.S. did not have the highest overall syphilis rates
PRIMARY AND SECONDARY SYPHILIS — RATES
OF REPORTED CASES BY STATE, 2013
http://www.cdc.gov/std/stats13/figures/34.htm
SOUTH DAKOTA, 2013
Ranked 15th of 50 States
5.3 cases per 100,000
Race/Ethnicity
per 100,000
population
• 2.4 among Whites
• 7.5 among Blacks
• 11.7 among Hispanics
• 31.1 among American Indians/Alaska
Natives
PRIMARY AND SECONDARY SYPHILIS — RATES OF
REPORTED CASES BY COUNTY, 2013
http://www.cdc.gov/std/stats13/figures/35.htm
INCIDENCE OF SYPHILIS
South Dakota
Department of
Health June 2014
Public Health
Bulletin discusses
“Heterosexual
Syphilis Outbreak
in North and South
Dakota”
Increasing
Incidence
• 2012: mostly homosexual
men
• 2013: a shift toward
heterosexual
• 2014: First case of congenital
syphilis in decades
• June 2014: mostly
heterosexual
SOUTH DAKOTA
PAST 10 YEARS
Early syphilis cases
76
49
21
19
Early syphilis cases
11
0
4 2 4
0
2005
2006
2007
2008
2009
2010
2011
2012
2013
2014
80
70
60
50
40
30
20
10
0
https://doh.sd.gov/documents/statistics/ID/July2015.pdf
SOUTH DAKOTA, 2015
EARLY SYPHILIS
Case by month, 2015
30
23
25
20
Mar
April
19
13
15
10
16
17
25
8
5
0
Jan
Feb
May
Jun
2015 Cumulative
https://doh.sd.gov/documents/statistics/ID/July2015.pdf
July
SOUTH DAKOTA, 2015
Regions
Sioux Falls Area
Rapid City Area
Northeast
Southeast
Central
West
South Dakota
Cases
Rate**
12
2
2
1
7
1
25
4.8
1.5
1.2
0.9
7.5
1.1
2.9
**Rate: cases per 100,000 population
https://doh.sd.gov/documents/statistics/ID/July2015.pdf
DEFINITIONS
Primary: one or more
ulcerative lesions
• The sore or chancre is
usually firm, round, small
& painless
• Occur 3 weeks after contact
http://www.cdc.gov/std/syphilis/images/chancre-oral.htm
DEFINITIONS
Secondary or Disseminated
• 4-10 weeks after initial primary lesion
• Rash can be local or diffuse
• Typically rough, red/brown on hands/bottoms of feet
• Headache, fever, weight loss, anorexia, fatigue
• Generalized lymphadenopathy
• Preterm labor
• Less common symptoms (alopecia, hepatitis, nephritic
syndrome, osteitis, iritis, meningitis )
SECONDARY SYPHILIS
http://www.cdc.gov/std/syphilis/images/rash-palmar.htm
TERTIARY SYPHILIS
• Cardiovascular manifestations
• Gummatous Lesions
http://jama.jamanetwork.com/article.aspx?articleid=183407
NEUROSYPHILIS
• Can occur during any stage
• Common in the early stage & can be without
clinical neurological findings
• Symptoms include cognitive dysfunction, motor,
sensory, ophthalmic, or auditory deficits, cranial
nerve palsies, and symptoms of meningitis
• Examine CSF
LATENT SYPHILIS
No clinical
symptoms
&
Serologic
reactive
• Early Latent
• 1 year or less from onset
• Late Latent
• >1 year from onset
• noninfectious
PATHOPHYSIOLOGY
Treponemes are able to cross placenta
30-40% of stillbirths are infected with
syphilis
Kassowitz’s law=vertical transmission
decreases as maternal disease progresses
T. pallidum is not transferred in breast
milk but may transfer if lesion on breast
PATHOPHYSIOLOGY
Absence of
primary stage
Widespread
involvement
Lymphocytes
Plasma cells
Histiocytes
Endarteritis &
extensive
fibrosis
DIFFERENTIAL DIAGNOSIS
Vesiculobullous
Lesions
Hepatosplenomegaly
Hydrops Fetalis
• Bacterial infections
• Viral infections
• Fungal infections
• Heredity disorders
• Isoimmunization
• Infectious Diseases
• Neonatal hepatitis
• Diseases of Biliary Tract
• Genetic & Metabolic Disorders
• Infectious Diseases
• Isoimmunization
• Chronic Anemia
• AVM, CCAM
• Perinatal Tumors, Renal Disorders, Achondroplaisa
DIAGNOSTIC
CONSIDERATIONS
A presumptive diagnosis:
• Nonspecific nontreponemal tests or NTA (INDIRECT
MEASURE)
• Test for biomarkers that are released during
cellular damage from the syphilis spirochete
• RPR, VDRL
• During early & late syphilis may be negative
• False Positives
NON TREPONEMAL
ANTIBODY TESTS
• RPR or VDRL titers correlate with disease activity
• A titer of at least 2 dilutions (4 fold higher) in the
infant than the mother signifies probably infection
• A 4 fold decrease in titer is typical of adequate
therapy
• Typically decreases 4 fold 6-12 months after therapy
• 1/3 become non reactive in 1 year
• VDRL should be used on CSF
DIAGNOSTIC
CONSIDERATIONS
A confirmatory diagnosis:
•Specific Treponemal tests (STA)
•Will be positive for life
•FTA-ABS, TP-PA, MHA-TP
•Various EIAs
DIAGNOSTIC
CONSIDERATIONS
A confirmatory diagnosis:
• Direct identification of T. pallidum of
body fluid
• Microscopic dark field examination
• Direct Fluorescent Antibody Staining
• PCR test to detect spirochete
TREATMENT
Follow algorithm for Evaluation
and Treatment of Infants born to
mothers with reactive serologic
tests for syphilis (AAP Red Book,
2012)
EVALUATE & TREAT
INFANTS WITH PROVEN/PROBABLE SYPHILIS
Evaluation
includes
• CBC
• Platelet count
• CSF: protein, cell count, VDRL
• Chest radiograph
• Eye examination
• Liver Function Tests
• Neuroimaging
• Hearing screen
TREATMENT
INFANTS WITH PROVEN/PROBABLE SYPHILIS
Penicillin G for 10 days
IV=50,000 units/kg q 12
hours (7 days) than q 8
hours
IM=50,000
U/kg/dose daily
Neurosyphilis
14 days of
treatment
TREATMENT
ASYMPTOMATIC INFANTS WITH
NORMAL EXAM & <4 FOLD TITER
Maternal treatment
uncertain
• Full Evaluation
• Option 1: Treat
with Pen G
• Option 2: Pen G
IM dose x1 with
follow up &
evaluation
Adequate maternal
treatment
• No evaluation
• Pen G IM dose x 1
recommended
INFANT SCREENING
Prior to
discharge
of ALL
infants:
• Determine maternal serologic
status for syphilis at least once
during pregnancy
• Testing of umbilical cord blood of
infant serum is NOT adequate
• Same NTA test on mother &
infant to compare titers
CONGENITAL SYPHILIS IS
PREVENTABLE WITH
ADEQUATE MATERNAL
TREATMENT!
PREVENTION
• NEW Department of Health
Recommendations
• Treat first and test second
• Add RPR to any STD panel or HIV testing
• ALL pregnant women should be screened 3 times
• First prenatal visit
• 3rd trimester
• Day of delivery
PREVENTION
• NEW Department of Health
Recommendations
• Any still born infant >20 weeks
should be tested for Syphilis
• Pregnant syphilis positive women
should be treated with Penicillin
QUESTIONS/ADDITIONAL
INFORMATION?
• Amanda Gill, M.S.
• SD Department of Health
• STD Program Manager
• Office 605-773-4794
• Email [email protected]
http://www.catie.ca/syphilis
BIBLIOGRAPHY
1.
Baker, C. J. (2013, June). Red Book Atlas of Pediatric Infectious Diseases (2 nd ed.). Elk Grove Village, IL: American
Academy of Pediatrics, 501-515.
2.
Centers for Disease Control and Prevention Patton, M. E., Su., J. R., N. R., & Weinstock. H. (2014). Primary and
Secondary Syphilis-United States 2005, 2013. Morbidity Mortality Weekly Report, 63 (18), 402-406.
3.
CDC (2015, August) Retrieved from http://www.cdc.gov/std/tg2015/syphilis.htm
4.
Chakraborty, R., & Luck, S. (2008). Syphilis is on the increase: the implications for child health. Archives of
Disease in Childhood, 93, 105-109.
5.
Gomella, T. L., Cunningham, M. D., Eyal, F. G., & Tuttle, D. J. (2013). Neonatology: Management, procedures, oncall problems, diseases, and drugs (7 th ed.). United States: McGraw-Hill Education.
6.
Herremans, T., Kortbeek, L., & Notermans, D. W. (2010). A review of diagnostic tests for congenital syphilis in
newborns. European Journal of Clinical Microbiology & Infectious Diseases, 29 (5), 495-501.
7.
South Dakota Department of Public Health. (2014, June). Heterosexual Syphilis Outbreak in North and South
Dakota, 26 (3), 1-2.
8.
Pickering, L. K., Baker, C. J., Kimberlin, D. W., & Long, S.S. (2012). AAP Red Book (29 th ed.). Elk Grove Village, IL:
American Academy of Pediatrics, 690-903.
9.
Remington, J. S., Klein, J. O., Wilson, C. B., & Baker, C. J. (2006). Infectious diseases of the fetus and Newborn
Infant (6 th ed.). Philadephia, PA: Elsevier Saunders.
10. South Dakota Department of Health. (2015, April). Retrieved from
https://doh.sd.gov/statistics/surveillance/default.aspx