STDs in Children

1
STDs in Children

• Marcus DeGraw, MD
• Medical Director Child Protection Team
• Medical Director Pediatric Subspecialty
  Services
• St. John Hospital
• Detroit, MI

2
STD identification in childrenDifferences
compared to adult testing

• Infection may indicate sexual abuse
• Non-sexual transmission must be considered
• Diagnostic errors can easily occur
• Clinical presentation can differ
• Forensic issues must be addressed
• Treatment must factor patients age

3
Infection may indicate sexual abuse

• Almost always
• GC, Chlamydia, Syphilis, HIV
• Suspicious
• HPV, HSV, hepatitis B, Trichomonas
• Inconclusive
• Gardnerella vaginalis (bacterial vaginosis)

4
Non-sexual transmission must be considered

• Infection through infected birth canal
• Gonorrhea, Chlamydia, HPV,HSV, Trichomonas
• Infection through trans-placental route
• HIV, syphilis
• Infection through fomites
• HPV, HSV

5
Diagnostic errors occur in populations with lower
disease prevalence

• Positive Predictive Value (PPV) a / (a b)
• Likelihood that a test is a true infection
• Dependent on prevalence
• STD prevalence is 2-13
• Prevalence Sensitivity Specificity PPV
• 20 90 98 92
• 5 90 98 70

6
Nucleic acid amplification tests Screening and
diagnosis applications

• LCR used opa gene (up to 11 copies/organism)
• Unique 48 base pair region is used
• Amplification is logarithmic
• 1 target ? 30-40 amplifications ? 1
  billion targets

7
Using nucleic acid amplification tests in cases
of sexual crimes

• These tests have increased sensitivity compared
  to culture and therefore have significant
  advantageous
• Positive tests must be verified by at least one
  additional test
• Culture is preferred (more than one may be
  needed)
• A second nucleic acid amplification test
  targeting a different sequence
• EIA, non-amplified probes and DFA anti-body tests
  are not acceptable because of their low
  specificities

8
Neisseria gonorrhea FAQ

• 600,000 new infections / year in U.S.
• Almost all men, but not women, are symptomatic
• Almost all pre-pubertal vaginitis is symptomatic
• Almost certainly sexually transmitted in children
• Perinatal infection to eye, vagina, urethra,
  rectum
• Culture is the gold standard

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Culture Identification of GCChildren who are
not sexually active

• Rayon or Dacron tipped swabs
• Plate on appropriate media immediately or
  transport within 12 hour in swab-tube transport
  system
• Initial lab ID of Neisseria species
• gram - diplococci w/adjacent sides flattened
• oxidase positive
• Confirm with 2 other tests using different
  principles
• DNA amplification / biochemical / enzyme
  substrate
• Samples should be preserved for later analysis

10
Selective GC testing

• Signs or symptoms of an STD
• Adolescent patient or perpetrator
• Alleged offender has or is high risk for STD
• Family is anxious about possibility of STD
• Follow-up is unlikely
• History or exam suggests penetration?

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Limited GC testingSiegel, Schubert, Myers,
Shapiro, Pediatrics 1995961090-1094

• GC Prevalence
• All girls 3.1
• Pubertal girls 4.6
• 50 - no symptoms
• Pre-pubertal girls 2.4
• 100 w/ vaginal discharge
• 11 of the pre-pubertal girls with discharge were
  infected with GC

• GC cultures in 379 pts
• 249 pre-pubertal girls
• 130 pubertal girls
• 12 GC infections

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Limited GC testingMuram, Speck, Dockter J
Pediatric Adolesc Med 96979-80

• GC Prevalence
• pre-pubertal girls
• 12 cultures 1.4
• all had vulvovaginitis
• adults
• 153 cultures 5.6

• GC cultures in
• 865 prepubertal girls
• 2743 adult women

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Limited GC testingIngram, Everett, Flick,
Russell, White-Sims Pediatrics 9799(6)

• 84 girls had GC infections
• 80 had a vaginal discharge
• 4 without discharge
• 2 had contact with perpetrator known to have GC
• 1 GC isolated from urine culture
• 1 had a sister (lt 12y/o) with GC infection

• 2731 GC cultures in girls
• all under age 12

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GC treatment

• Ciprofloxacin 500mg po (99.8 cure rate)
• Ceftriaxone 125mg IM only approved drug (99.1)
• Cefixime 400mg po (97.4)
• Pharyngeal GC rx Cipro or Ceftriaxone
• Follow-up cultures are optional consider legal
  implications of test for cure
• Ascending infection rare in pre-pubertal children

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Chlamydia trachomatis FAQ

• Non-motile gram negative bacteria
• Obligate intracellular cycle (cannot synthesize
  ATP)
• infect columnar epithelial cells
• Form distinct intracellular inclusions
• Most common STD in U.S
• 70 women 50 men asymptomatic infections

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Chlamydia trachomatis infection

• Neonates
• common cause of conjunctivitis and pneumonia
• vagina, urethra and rectum can be infected
• asymptomatic infection may last 2-3 years old (or
  longer)
• Hammerschlag 1994 Ped Ann 23349-353
• 65 of infants infected after peri-natal exposure
• Children
• 2-13 prevalence in sexually abused children
• GU and rectal infections usually indicate abuse
• Pharynx not usually tested because infection is
  uncommon, perinatal infection may persist and lab
  may have difficulty distinguishing between C.
  trachomatis with C. pneumonia

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Testing for C. trachomatis

• cell culture
• nucleic acid amplification tests
• antigen detection tests
• nucleic acid detection tests
• serologic tests
• specificity
• sensitivity
• legal acceptance and gold standards

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Chlamydia Cell culture

• The Gold Standard - specificity near 100
• only proven test in suspected abuse
• Sensitivity 70-85 compared to DNA amplification
• Cold and rapid transport of specimen is critical
• Technique
• specimens are inoculated onto cell culture
• within 48-72 hr., fluorescein-labeled antibodies
  bind to chlamydia lipopolysaccharide or major
  outer membrane protein

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Chlamydia cell culture technique

• Include infected host cells in the specimen
• Avoid swabs with wood shafts
• Use tips of dacron, cotton, rayon or calcium
  alginate
• Use approved transport media and transport to lab
  immediately
• Refrigerate at 2o to 8o C and process within 48
  hr.
• Freeze at -70o C if cannot process in 48 hr.
• freezing will reduce sensitivity by at least 20

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Nucleic acid amplificationPCR(Polymerase Chain
Reaction) LCR(Ligase Chain Reaction)

• Sensitivity (can detect single gene copy)
• 90-96 (less than 100 due to inhibitors in
  specimen)
• Specificity
• 99-100 (false positives most likely to originate
  in lab)
• Limited data available for pre-pubertal children
• May be an acceptable as a screening test
• positive tests need to be confirmed
• Vaginal swabs more sensitive than urine assays

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Diagnosis of Chlamydia trachomatis GU infection
in women by LCR assay of urine Lee, Chernesky,
Schachter et al. Lancet 1995 345213-26

• 1937 women
• Obtained samples of
• first void urine (FVU)
• endocervical swabs
• Cultured for chlamydia from endocervical swabs
• LCR performed on FVU
• Expanded Gold Standard

• Sensitivity
• 65 culture
• 93.8 LCR
• Specificity
• 100 culture
• 99.9 LCR
• LCR detection rate in FVU was 30 greater than
  culture

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Chlamydia Serologic testing

• Antibodies are long lived and IgM rise often not
  seen in GU infections
• Difficult to distinguish recent infections from
  old
• Test may not be species specific
• May detect Chlamydia other than trachomatis

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Chlamydia treatment

• Children 6 mo - 12 years old
• Azithromycin 1gm x 1 dose
• Children lt 6 mo
• Erythromycin 40mg/kg/day x 7 days (80 effective)
• Other options (but less effective)
• Amoxicillin
• Sulfisoxazole
• Ascending infection is rare in pre-pubertal
  children

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Genital Ulcers

• HSV, syphilis, chancroid
• Not all genital ulcers are caused by STD
• 25 patients have no confirmed diagnosis
• Clinical diagnosis is inaccurate and insensitive
• Syphilis serology and/or darkfield exam
• HSV culture or antigen detection, HSV-2 serology?
• Haemophilus ducreyi culture if indicated
• Biopsy if unresolved

25
Herpes Simplex Virus (HSV) FAQ

• Genital HSV infection is life long
• HSV-2, compared to HSV-1, is more often recurrent
• 30 1st time GU infections are HSV-1
• Most infected persons have not been diagnosed
• Most infections transmitted by persons unaware
• Rectal / GU infection in children may indicate
  abuse

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Children with HSVLikelihood of Sexual Abuse
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Testing for HSV

• Culture is preferred when lesions are present
• Sensitivity decreases as lesions begin to heal
• Staining with monoclonal antibodies increases
  specificity and provides HSV-1 / HSV-2 typing
• Antigen detection testing of lesions by DFA
• PCR may be available limited knowledge re
  reliability
• Tzanck preparations are insensitive and
  nonspecific
• Serologic tests (80-96 sensitive, 96 specific)
• Must identify HSV specific glycoprotein
• G1 (HSV-1) and G2 (HSV-2)
• Some labs use other testing that is inaccurate

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HSV Specimen Collection

• Vesicles have large amounts of virus
• aspirate w/ fine gauge needle TB syringe or
  unroof the vesicle and scrape base
• Ulcers or pustules can also be cultured
• clean first with sterile saline
• swab base vigorously
• Dacron swabs are best
• calcium alginate swabs inhibit HSV growth

29
Syphilis FAQ

• Treponema pallidum never grown artificially
• Infection by direct contact only
• Almost always sexually transmitted after newborn
  period
• Preferred treatment - Penicillin G
• limited info regardomg other Rx
• Doxycycline x 14 days, Ceftriaxone x 10 days,
  Azithromycin 2 gm
• 1o syphilis
• incubation period 3 weeks (range 10 - 90 days)
• chancre occurs at the site of inoculation

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Testing for syphilis

• Dark field exam and DFA antibody tests on exudate
• Serologic tests
• Initially negative will become in 1-3 months
• Non-treponemal tests (VDRL and RPR)
• tests are negative after treatment
• Treponemal tests (FTA-ABS and TP-PA)
• titers correlate with disease activity, usually
  reactive for life
• Diagnosis difficult in infants lt 18 mo

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Secondary Syphilis

• 6 wk. - 6 mo after 1o lesion
• Clinical manifestations
• polymorphic rash, often M-P on palms/soles
• condylomata lata around anus or vulva
• hypertrophic, papular lesion
• systemic systems
• lymphadenopathy, fever, malaise, splenomegaly,
  sore throat, H/A, arthralgias, CNS involvement
• Resolves in 4 - 12 weeks

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Chancroid FAQ

• Clinical presentation
• One or more painful genital ulcers
• Regional, tender lymphadenopathy
• Both present in 30 only patients
• Laboratory diagnosis
• Culture for H. ducreyi (not readily available)
• Sensitivity only 80
• No evidence of syphilis (must delay serology
  testing)
• Negative culture/antigen for HSV-2
• Azithromycin, Ceftriaxone, Cipro, Erythromycin

33
Human Papillomavirus HPV FAQ

• Genital HPV is a viral infection
• Almost always sexually transmitted in adults
• More than 30 types infect the GU tract
• Most infections are subclinical and unrecognized
• Incubation period is variable - 2 years or more
• Diagnosis is clinical, biopsy can be obtained
• External warts are usually not associated with
  cancer
• Types 16, 18, 31, 33 35 - strongly associated
  with cervical neoplasia
• Recurrence within months usually is not
  re-infection

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Children with HPV Likelihood of Sexual Abuse
35
Diagnosis of sexual abuse in children with HPV

• Transmission in children include
• Perinatal, autoinoculation, fomites, sexual abuse
• Intra-anal warts are seen predominantly in
  patients who have had receptive anal intercourse
• Perianal warts are frequently seen in patients
  who do not
• Work-up for abuse is indicated when HPV is found
• Subclinical infection noted with 3 acetic acid
• HPV infected mucosal tissue becomes whitish in
  color
• Not specific test for HPV

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Treatment of HPV

• Watchful waiting
• External solutions
• Cryotherapy
• Laser surgery
• Surgical removal
• Intralesional interferon

37
T. vaginalis FAQ (Trichomonas)

• Most infected males have no symptoms
• Many infected woman have malodorous discharge
  while others are asymptomatic
• Diagnosis by microscopy is 60 - 70 sensitive
• Culture is the most sensitive diagnostic method
• Metronidazole cure rate is 90 - 95 in adults
• Infection in children is very suspicious for abuse

38
Hepatitis B FAQ

• Onset of symptoms after infection is 6 wks 6 mo
• Most adult infections are sexually transmitted
• HBsAg present in acute and chronic infections
• IgM anti-HBc diagnostic of acute infections
• Anti-HBs after resolution or immunization
• After acute sexual assault
• HB vaccine if patient is unvaccinated
• Add HBIG if perp is HBV ( 0.06 mL/kg within 14
  days)
• No vaccine or effective prophylaxis available for
  Hepatitis C

39
HIV FAQ

• Time from infection and AIDS months 17 years
• Prompt diagnosis is indicated for optimal care
• Informed consent needed before testing
• HIV antibody (EIA) confirmed by Western Blot
• 95 infected patients will be by 3 months
• On-site counseling must be provided if infected
• Diagnosis in infants lt18 mo is difficult
• Maternal antibody crosses the placenta
• HIV in blood by culture, nucleic acid or antigen

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Pediculosis Pubis (public lice) FAQ

• Usually transmitted by sexual contact
• Lice in the eyelashes are also pediculosis pubis
• Screen all infected children for sexual abuse
• Treat eyelash infestation with occlusive
  ophthalmic ointment BID x 10 days

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Acute and high risk sexual abuseWhat tests to
obtain

• At time of evaluation consider
• GU and rectal GC and chlamydia testing
• Pharyngeal GC testing
• Culture for T. vaginalis
• Serum for HIV, syphilis and Hepatitis B
• In 2 weeks first time or repeat testing if not
  treated
• In 6 weeks syphilis serology
• In 3 months HIV serology
• In 6 months HIV serology

42
Chronic low risk abuse testing Presumptive
Treatment

• History, exam findings, parental/patient anxiety
  and demographic history dictate the extent of
  testing
• Presumptive treatment for GC and chlamydia are
  not indicated in pre-pubertal children
• Adolescent patients should be offered treatment
  at the time of the acute assault
• Risk for HIV must be considered within 72 hours
  of an acute assault