Mary K. Sawyer

Epidemiology of Human Papillomavirus Infection and Abnormal Cytologic Test Results in an Urban Adolescent Population

We determined the prevalence of and the risk factors for human papillomavirus (HPV) infection and abnormal cytologic test results in 312 adolescent girls (mean age, 16.1 years). Subjects had a median of 2 years of sexual activity and 4 lifetime sex partners. Cervical HPV was detected by use of L1-consensus polymerase chain reaction in 64% of subjects; half of those with HPV had >1 type, and 77% had >/=1 high-risk type. Independent risk factors for HPV were lifetime number of sex partners, age of partner, and douching. Cytologic abnormalities were common (20.9% of subjects had atypical squamous cells of uncertain significance, and 17.0% had high- or low-grade squamous intraepithelial lesions) and were significantly associated with detection of HPV (P=.0001); however, most (51.6%) subjects with HPV had normal cytologic test results.

Trichomonas vaginalis prevalence, incidence, risk factors and antibiotic-resistance in an adolescent population.

Objective: To determine the prevalence and incidence of trichomoniasis, risk factors for infection, and the prevalence of metronidazole- and tinidazole-resistant Trichomonas vaginalis (T. vaginalis) in female adolescents. Methods: Nonpregnant, HIV-seronegative, sexually active females (13–19 years) visiting an inner city public primary care clinic were tested for T. vaginalis by wet mount and culture, and interviewed about risk-taking behavior every 6 months. Infected patients were treated with a 2 g oral dose of metronidazole. Isolates from positive T. vaginalis cultures were tested for in vitro resistance to metronidazole and tinidazole. Results: Among 467 study participants, 67 (14.4%; 95% confidence interval, 11.3–17.5) were diagnosed with trichomoniasis at first T. vaginalis culture. Significant risk factors for T. vaginalis infection were having an older sex partner and concurrent Neisseria gonorrhoeae infection. The incidence was 22.1 cases per 100 person-years. Among 42 participants who had a prevalent infection and returned for follow-up, 13 (31.0%) had at least 1 more episode of trichomoniasis. Resistance testing was completed for 78 isolates: 37 at first visit and 41 during follow-up. One (2.7%; 95% confidence interval, 0.07–14.2) of the 37 first-visit isolates was moderately resistant to metronidazole (minimal lethal concentration = 200 &mgr;g/mL). Of the 41 follow-up visit isolates, 1 was moderately resistant to metronidazole and 2 had borderline resistance (minimal lethal concentration = 50 &mgr;g/mL). The prevalence of tinidazole resistance was 0% (0.0%–9.5%). Conclusion: The study population had high prevalence and incidence of trichomoniasis. The prevalence of antibiotic-resistant T. vaginalis among female adolescents was low.

Multicenter study of nucleic acid amplification tests for detection of Chlamydia trachomatis and Neisseria gonorrhoeae in children being evaluated for sexual abuse.

Background: Diagnosis of sexually transmitted infections in children suspected of sexual abuse is challenging due to the medico-legal implications of test results. Currently, the forensic standard for diagnosis of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections is culture. In adults, nucleic acid amplification tests (NAATs) are superior to culture for CT, but these tests have been insufficiently evaluated in pediatric populations for forensic purposes. Methods: We evaluated the use of NAATs, using urine and genital swabs versus culture for diagnosis of CT and NG in children evaluated for sexual abuse in 4 US cities. Urine and a genital swab were collected for CT and NG NAATs along with routine cultures. NAAT positives were confirmed by PCR, using an alternate target. Results: Prevalence of infection among 485 female children were 2.7% for CT and 3.3% for NG by NAAT. The sensitivity of urine NAATs for CT and NG relative to vaginal culture was 100%. Eight participants with CT-positive and 4 with NG-positive NAATs had negative culture results (P = 0.018 for CT urine NAATs vs. culture). There were 24 of 485 (4.9%) female participants with a positive NAAT for CT or NG or both versus 16 of 485 (3.3%) with a positive culture for either, resulting in a 33% increase in children with a positive diagnosis. Conclusions: These results suggest that NAATs on urine, with confirmation, are adequate for use as a new forensic standard for diagnosis of CT and NG in children suspected of sexual abuse. Urine NAATs offer a clear advantage over culture in sensitivity and are less invasive than swabs, reducing patient trauma and discomfort.

Serologic response to hepatitis B vaccine in HIV infected and high-risk HIV uninfected adolescents in the REACH cohort

PURPOSE To evaluate hepatitis B (HBV) vaccine response rates in HIV infected and high-risk HIV uninfected youth and examine associations with responsiveness in the HIV infected group. METHODS Cohorts within the Reaching for Excellence in Adolescent Care and Health (REACH) study population were defined based on receipt of HBV vaccine both retrospectively and prospectively. Sero-responsiveness was determined by HBsAb measurements. Testing was done for HBsAg, HBsAb, and HBcAb. For HBsAb, a value of > 10 International Units per liter was considered a positive response, and the data were collected as either positive or negative from each of the reporting laboratories. Covariates of responsiveness were explored in univariate and multivariate models for each cohort. RESULTS Sixty-one subjects had received a three-dose vaccination course at the time of entry into REACH. HIV uninfected subjects had significantly higher rates of response by serology compared with HIV infected subjects (70% vs. 41.1%; chi(2) = .05; RR = .586, 95% CI: .36-.96). By the time of an annual visit 43 subjects had received three vaccinations with at least one occurring in the study period. The rates of response were similar for the HIV infected and uninfected groups (37.1% vs. 37.5%) in this cohort. Univariate and multivariate analysis in the prospective HIV infected group (N = 35) found an association between elevated CD8(+)/CD38(+)/HLA-DR(+) T cells and lack of HBV vaccine responsiveness (6.7% vs. 60%; chi(2) = .03; RR = .12, 95% CI: .02- .55). CONCLUSIONS The poor HBV vaccine response rate in the HIV uninfected high-risk adolescents was unexpected and suggests that HBV vaccination doses have not been optimized for older adolescents. This is the first report of decreased responsiveness in HIV infected subjects being associated with elevated CD8(+)/CD38(+)/HLA(-)DR(+) T cells and suggests that ongoing viral replication and concomitant immune system activation decreases the ability of the immune system in HIV infected subjects to respond to vaccination.

Comparison of Methods for Detection of Chlamydia trachomatis and Neisseria gonorrhoeae Using Commercially Available Nucleic Acid Amplification Tests and a Liquid Pap Smear Medium

ABSTRACT Annual screening for Chlamydia trachomatis infection is currently recommended for sexually active women 15 to 25 years old and for women older than 25 if they have a new or multiple sex partners and have not used condoms during the previous 3 months. Annual screening for cervical abnormalities using the Pap smear has achieved a substantial reduction in morbidity and mortality from cervical cancer. Screening for Neisseria gonorrhoeae infection has likely contributed significantly to the reduction in the rates of gonococcal infection. The introduction of liquid Pap smear methods using exfoliated cervical cells presents an opportunity to screen for these three conditions using one specimen. We evaluated the preservation of C. trachomatis and Neisseria gonorrhoeae DNAs from ThinPrep liquid media (PreservCyt; Cytyc Corp., Boxborough, Mass.); tested the feasibility of using a clinical specimen of this medium for the detection of cytologic abnormalities, C. trachomatis, and N. gonorrhoeae; evaluated the agreement between ligase chain reaction (LCR) performed on PreservCyt and LCR performed on a cervical specimen; and compared the performance of LCR performed on PreservCyt to those of LCR performed on a cervical specimen, culture, PCR performed on a cervical specimen, on urine, and on a vaginal specimen (a multiple-site infection status standard), and transcription-mediated amplification (for C. trachomatis only) from 255 sexually active adolescent women. The agreement between LCR performed on PreservCyt and LCR from a cervical swab in LCx transport medium was high (for C. trachomatis, agreement = 0.97 and kappa = 0.92; for N. gonorrhoeae, agreement = 0.99 and kappa = 0.96). Test performances were similar for LCR-urine, LCR-cervix, and LCR-ThinPrep, with sensitivities from 93 to 99% for C. trachomatis and 81 to 83% for N. gonorrhoeae and specificities from 95.5 to 99% for C. trachomatis and 99.1 to 99.6% for N. gonorrhoeae using a PCR-based multiple-site infection status standard. This is the first study to examine the agreement between liquid cytologic media and multiple nucleic acid amplification tests for the detection of C. trachomatis and N. gonorrhoeae from patient samples. Cytologic fluid shows promise for simultaneous screening for cytologic abnormalities and sexually transmitted infections.

A prospective population-based study of HIV perinatal transmission.

Objective:To estimate the perinatal HIV transmission rate and describe the natural history of infant HIV infection in a situation in which HIV status is known in more than 95% of delivering women. Design:A cohort of HIV-exposed infants born between 7 July 1987 and 30 June 1990, whose mothers were identified by routine voluntary universal HIV testing, were followed using clinical and laboratory measures. Setting:Grady Memorial Hospital, a major health-care site for individuals of lower socioeconomic status in Atlanta, Georgia, USA, with approximately 7000 deliveries per year. Patients:HIV-exposed infants (n=165), 98% of whom were African American. Results:Annual maternal HIV seroprevalence increased from 0.58 to 0.86%. The annual proportion of HIV-positive women having a second delivery increased from 4.3 to 25%. Clinical outcome was known for 132 out of 165 infants (22 infected and 110 uninfected), the transmission rate was 17% (confidence interval, 11–24%). The rate declined to 11% by the third year of the study. Gestational growth, prematurity and mode of delivery were unrelated to infant outcome. There was a trend for intravenous drug use to be more common in mothers of infected infants (P=0.08). After 35 months median follow-up of infected infants, eight out of 22 (36%) had an opportunistic infection (seven Pneumocystis carinii pneumonia); three out of 22 (14%) had lymphocytic interstitial pneumonia, and 10 out of 22 (45%) were asymptomatic or had only nonspecific symptoms. Cumulative mortality in infected infants was 9, 32 and 32% by 1, 2 and 3 years of age, respectively. Conclusion:In this cohort of HIV-exposed infants, perinatal HIV transmission was 17% overall. Factors affecting the transmission rate and possible future changes in the rate require further study.

Diagnosis of Perinatal Human Immunodeficiency Virus Infection by Polymerase Chain Reaction and p24 Antigen Detection after Immune Complex Dissociation in an Urban Community Hospital

Results of polymerase chain reaction (PCR) and p24 antigen detection after immune complex dissociation (p24-ICD) were compared with antibody results after 18 months of age for human immunodeficiency virus (HIV) diagnosis in 345 prospectively followed, perinatally exposed infants. Of 59 infected and 286 uninfected infants tested at 1-6 months of age, sensitivity and specificity were, respectively, 100% and > 97% for PCR and 90% and > 97% for p24-ICD. Testing was done on > or = 2 occasions in the first 6 months of life in 43 infected infants; 77% had > or = 2 positive results with the same test. Of these infants, 68% had 2 positive p24-ICD tests. In uninfected infants, 96% had only negative tests; none had > 1 positive. By 6 months, all uninfected infants with > or = 2 PCR results could have been diagnosed. HIV status can be determined by PCR by age 6 months in most HIV-exposed infants. p24-ICD should not be used alone, because of its lower sensitivity, but may be useful in areas without advanced laboratory support.

Evaluation of the rapid BioStar optical immunoassay for detection of Chlamydia trachomatis in adolescent women.

ABSTRACT We evaluated the performance of the BioStar Chlamydia OIA (optical immunoassay) in adolescent females (n = 261) from an inner city population. With a reference standard of two different nucleic acid amplification tests, the sensitivity and specificity of the BioStar Chlamydia OIA were 59.4 and 98.4%, respectively. Due to its relatively low sensitivity, the BioStar Chlamydia OIA should only be used in conjunction with more sensitive laboratory tests unless laboratory tests are unavailable or timely return for treatment is unlikely.

Varicella in children with perinatally acquired human immunodeficiency virus infection

Thirteen children with human immunodeficiency virus infection acquired perinatally and with varicella were identified. Clinical and epidemiologic information, including the use of varicella immune globulin and acyclovir, was obtained and testing for antibodies to varicella-zoster virus was done. The 13 children infected with human immunodeficiency virus had an uncomplicated clinical course, and many had a significant antibody response to varicella-zoster virus.

Anogenital Human Papillomavirus in Sexually Abused and Nonabused Children: A Multicenter Study

OBJECTIVES: To characterize the epidemiology of genital human papillomavirus (HPV) infection in children without previous consensual sexual activity, comparing HPV prevalence by certainty of child sexual abuse (CSA). PATIENTS AND METHODS: Patients presenting for evaluation of CSA in 8 sites in Atlanta, Houston, Harrisburg, and New York City were recruited along with patients presenting for unrelated health visits. CSA certainty was classified as definite, probable, possible, or no evidence following published guidelines and the results of history, physical examination, and laboratory tests. Urine and swabs of external genitalia were tested for HPV using L1 consensus polymerase chain reaction. RESULTS: The study included 576 participants (89.9% female) aged 6 months to 13 years (mean: 7.9); 534 of whom were evaluated for CSA and 42 for unrelated reasons. Of those evaluated for CSA, 14 had genital warts. One or more HPV types were detected in 11.8% (61 of 517) of participants with adequate samples. HPV detection was more likely among abused participants (definite, probable, or possible) than among participants without evidence of CSA (13.7% and 1.3%, respectively; P < .0001) and increased with certainty of abuse (8.4%, 15.6%, and 14.5% in participants with possible, probable, and definite CSA, respectively; P < .0001). Participants aged 10 years or older had a higher prevalence of HPV (20.6%) than others (5.6%) (P < .0001). CSA, anogenital warts, and age were independently associated with HPV detection. CONCLUSIONS: HPV detection was associated with CSA and increased with CSA certainty. In this population, genital HPV seemed to behave as a sexually transmitted infection.