Biomedical subjects
Publications and source records attributed to Julius Schachter.
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Nucleic acid amplification tests (NAATs) for the detection of Chlamydia trachomatis are routinely used on first-catch urine (FCU) specimens. We analyzed data from a head-to-head comparison of NAATs on female FCU specimens and found that the volume of urine collected could affect test performance.
Because self-collected vaginal swabs (VS) are potentially very useful for screening asymptomatic women for Chlamydia trachomatis infection, a multicenter study evaluated that specimen with nucleic acid amplification tests (NAATs). The objective was to determine whether VS are equal to Food and Drug Administration (FDA)-cleared specimens (cervical swabs and first-catch urines [FCU]) for diagnosing genital chlamydial infection. All NAATs then commercially available (October 1996 to October 1999) were used (ligase chain reaction [LCx Probe System; Abbott Laboratories, Abbott Park, Ill.]; PCR [Amplicor; Roche Molecular Systems, Branchburg, N.J.]; and transcription-mediated amplification, [Amplified CT Assay; Gen-Probe Inc., San Diego, Calif.]). NAATs were performed on FCU, urethral, cervical, self- and clinician-collected VS. Sensitivity was compared to isolation using cervical and urethral swabs. Agreement of NAAT results between VS and cervical swabs or FCU was calculated. Specimens from 2,517 15- to 25-year-old asymptomatic women attending clinics at nine different centers were evaluated. Results with self- and clinician-collected VS were equivalent and were at least as good as results with FCU and cervical swabs. Across all sites, summary specificities for all specimens were >99%. Among culture-positive women, NAAT sensitivity with VS (93%) was as high as or higher than NAAT sensitivity with cervical swabs (91%) or FCU (80.6%) or culture of cervical swabs (83.5%). VS are appropriate specimens for diagnosing chlamydial genital tract infection by NAATs. That patients can efficiently collect them offers important benefits for screening programs. It would be beneficial for public health programs if the NAAT manufacturers sought FDA clearance for this specimen.
We set out to determine the prevalences of Chlamydia trachomatis and Neisseria gonorrhoeae by ligase chain reaction as well as to determine the prevalence of Trichomonas vaginalis by culture in a large and diverse national sample of non-health-care-seeking young women entering the military; we also sought to compare the abilities of three different techniques of collecting specimens (first-void urine, self-collected vaginal swab, and clinician-collected endocervical swab) to identify a positive specimen. A cross-sectional sample of young women was voluntarily recruited; as a part of their routine entry pelvic examination visit, they completed a self-administered reproductive health questionnaire and provided first-void urine (used to detect C. trachomatis and N. gonorrhoeae) and self-collected vaginal swabs (used to detect C. trachomatis, N. gonorrhoeae, and T. vaginalis). The number of positive tests divided by the number of sexually active women screened by each sampling method determined the rates of prevalence. The rate of infection with any of the three sexually transmitted diseases (STDs) tested was 14.1%. The total positive rates for each STD (identified by >/=1 specimen) were the following: for C. trachomatis, 11.6%; N. gonorrhoeae, 2.4%; and T. vaginalis, 1.7%. The proportions of positives identified by specimen type were, for C. trachomatis and N. gonorrhoeae, respectively, endocervix, 65 and 40%; urine, 72 and 24%; and vagina, 81 and 72%. The proportions of positives when specimen results were combined were, for C. trachomatis and N. gonorrhoeae, respectively, cervix plus urine, 86 and 49%; cervix plus vagina, 91 and 93%; and vagina plus urine, 94 and 79%. We concluded that STDs were epidemic in this population. Self-collected vaginal swabs identified the highest number of positive test results among single specimens, with the combined cervix-vagina results identifying the highest number of positive results. Self-collected vaginal swab collections are a feasible alternative to cervical specimen collections in this population, and the use of multiple types of specimens increases the positive yield markedly.
We previously reported that laboratory reference strains of Chlamydia trachomatis differing in infection organotropism correlated with inactivating mutations in the pathogen's tryptophan synthase (trpBA) genes. Here, we have applied functional genomics to extend this work and find that the paradigm established for reference serovars also applies to clinical isolates - specifically, all ocular trachoma isolates tested have inactivating mutations in the synthase, whereas all genital isolates encode a functional enzyme. Moreover, functional enzyme activity was directly correlated to IFN-gamma resistance through an indole rescue mechanism. Hence, a strong selective pressure exists for genital strains to maintain a functional synthase capable of using indole for tryptophan biosynthesis. The fact that ocular serovars (serovar B) isolated from the genital tract were found to possess a functional synthase provided further persuasive evidence of this association. These results argue that there is an important host-parasite relationship between chlamydial genital strains and the human host that determines organotropism of infection and the pathophysiology of disease. We speculate that this relationship involves the production of indole by components of the vaginal microbial flora, allowing chlamydiae to escape IFN-gamma-mediated eradication and thus establish persistent infection.
The common wisdom is that a trachoma program cannot eliminate ocular chlamydia from a community, just reduce infection to a level where blindness would be minimal. We describe the success of multiple mass antibiotic treatments, demonstrating that complete elimination of infection may be an attainable goal in an area with modest disease.
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OBJECTIVE: To assess sexually active adolescents' attitudes toward 3 screening collection techniques for detection of Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis using first-void urine (FVU), self-collected vaginal swab specimens, and pelvic examination with clinician-collected endocervical swab specimens. DESIGN: Participants completed a preexamination health survey, provided FVU and self-collected vaginal swab samples, and had a pelvic examination with endocervical swab specimen collection. In a confidential postexamination interview, patients ranked the 3 screening techniques according to preference and responded to qualitative positive and negative descriptors to evaluate each technique. SETTING: San Francisco area health maintenance organization and university clinics. PARTICIPANTS: A convenience sample of 155 ethnically diverse females aged 12 to 21 years, who were sexually active and were to have a pelvic examination. MAIN OUTCOME MEASURES: Adolescents' preferences for and evaluations of 3 sexually transmitted disease screening techniques. RESULTS: Participants preferred the FVU test for sexually transmitted disease screening over the pelvic examination and the self-administered vaginal swab test (P<.001). These results were consistent when controlling for potentially mitigating experiences, including previous pelvic examination, tampon or condom use, and prior pregnancy. In evaluating what they liked and disliked about each of the 3 screening methods, participants described the FVU most positively, the pelvic examination most negatively, and the vaginal swab technique slightly less positively than the FVU. CONCLUSION: Most sexually active adolescents attending clinics for pelvic examination prefer to be screened for sexually transmitted diseases first by the FVU, second by the self-collected vaginal swab test, and last by the pelvic examination.
The WHO has initiated a global program to eliminate trachoma. This program includes mass antibiotic administrations to reduce the prevalence of Chlamydia trachomatis, the causative agent in trachoma. DNA amplification tests are the most sensitive methods to diagnose C. trachomatis infection, but are expensive and not typically performed in trachoma-endemic areas. Trachoma programs use clinical examination to determine which communities and which individuals within communities would benefit from antibiotic treatment, so understanding the relationship between clinical activity and chlamydial infection is important. In this study, we determine what percent of individuals with clinically active trachoma are infected with chlamydia in low prevalence communities of China and Nepal (with <10% clinical activity in children), and compare this against a high prevalence community of Nepal (with >30% clinical activity in children). In the low prevalence areas, only 8% clinically active cases had evidence of chlamydia. In the high prevalence community, 70% of clinically active cases harbored chlamydia. These results imply that clinical activity is less indicative of infection at a lower prevalence. In the context of a trachoma program, both clinically active cases and the community as a whole may stand to benefit less from antibiotic treatment in lower prevalence areas.
PURPOSE OF REVIEW: A recently initiated major effort to eliminate blinding trachoma as a public health problem is discussed. RECENT FINDINGS: Mass (community-wide) treatment with a short course of oral azithromycin has been shown to be at least as effective as long courses (42 doses over a 6-week period) of topical tetracycline in reducing clinically active trachoma and the prevalence of chlamydial infection. The beneficial effects last for more than a year, in contrast to the short-lived results typically seen after previous control programs that used topical therapy. Azithromycin is a key element in the integrated approach towards eliminating blinding trachoma summarized as the 'SAFE' strategy (surgery for deformed eyelids; antibiotic treatment of whole communities with azithromycin, to control infection; face washing and improved hygiene of young children; and environmental improvements, particularly the provision of water and latrines). The first regional application of this strategy has shown dramatic results, producing a reduction in trachoma activity of more than 70% in Morocco. SUMMARY: The goal of eliminating blinding trachoma may be reachable. Further research is needed to determine how best to use azithromycin and which environmental improvements will be most effective. The important questions are as follows: how often antibiotic treatment programs will be required in the endemic areas; how best to evaluate the effects of treatment; and when (and perhaps whom) do we retreat.
Few evaluations of tests for Chlamydia trachomatis have compared nucleic acid amplification tests (NAATs) with diagnostic tests other than those by culture. In a five-city study of 3,551 women, we compared the results of commercial ligase chain reaction (LCR) and PCR tests performed on cervical swabs and urine with the results of PACE 2 tests performed on cervical swabs, using independent reference standards that included both cervical swabs and urethral swab-urine specimens. Using cervical culture as a standard, the sensitivities of PACE 2, LCR, and PCR tests with cervical specimens were 78.1, 96.9, and 89.9%, respectively, and the specificities were 99.3, 97.5, and 98.2%, respectively. Using either cervical swab or urine LCR-positive tests as the standard decreased sensitivities to 60.8% for PACE 2 and to 75.8 and 74.9% for PCR with cervical swabs and urine, respectively. Specificities increased to 99.7% for PACE 2 and to 99.7 and 99.4% for PCR with cervical swabs and urine, respectively. Sensitivities with a cervical swab-urine PCR standard were 61.9% for PACE 2 and 85.5 and 80.8% for LCR with cervical swabs and urine, respectively. Specificities were 99.6% for PACE 2 and 99.0 and 98.9% for LCR with cervical swabs and urine, respectively. Cervical swab versus urine differences were significant only for PCR specificities (P = 0.034). Overall, LCR sensitivity exceeded that of PCR, and sensitivities obtained with cervical swabs exceeded those obtained with urine specimens by small amounts. These data have substantiated, using a large multicenter sample and a patient standard, that LCR and PCR tests performed on endocervical swabs and urine are superior to PACE 2 tests for screening C. trachomatis infections in women. In our study, NAATs improved the detection of infected women by 17 to 38% compared to PACE 2.
In a multicenter comparison of PCR assays utilizing 120 quantitated samples of 16 Chlamydia pneumoniae isolates, an LCx research-use-only (RUO) PCR developed by Abbott Laboratories demonstrated 100% sensitivity on 48 samples with >1 copy of DNA per microl of specimen. The sensitivities of five in-house PCR assays ranged from 54 to 94% for the same samples. All six assays showed decreased sensitivities as the DNA copy numbers of the samples decreased. Overall, sensitivities ranged from 68% for the LCx PCR assay to 29% for one of the in-house tests. The LCx RUO PCR and three of the five in-house PCR tests reported no false positives with the 24 negative samples. Increasing the number of replicates tested increased the sensitivities of all of the assays, including the LCx PCR. The LCx RUO assay showed high reproducibility for a single technologist and between technologists, with a kappa agreement of 0.77. The within-center agreements of the five in-house PCR tests varied from 0.19 to 0.74 on two challenges of 60 specimens 1 month apart. The LCx C. pneumoniae RUO PCR shows excellent potential for use in clinical studies, which could enable standardization of results in the field.
OBJECTIVE: To examine risk factors of sexually transmitted diseases (STDs) in a non-clinic-based sample of young male military personnel. METHODS: A total of 1,028 enlisted U.S. Marines completed a self-report survey querying sexual behaviors in the previous 3 months and provided urine specimens for STD screening by nucleic acid amplification testing for Chlamydia trachomatis and Neisseria gonorrhoeae. Risk for STDs was assessed using a composite Sexual Risk Index. Recent STD infection was defined as a positive result on urine-based screening for chlamydial and/or gonococcal infection and/or a history of STDs in the past 3 months. RESULTS: Recent STDs were identified in 76 men (7.4%): 42 (4.1%) were diagnosed with a chlamydial infection with no gonorrhea found, and 34 (3.3%) reported a history of STDs. Men with the highest score on the Sexual Risk Index were 2.6 times more likely to have a current STD compared with those at lowest risk (odds ratio = 2.6, confidence interval = 1.01, 6.2). CONCLUSIONS: Use of a composite measure of risk can identify the most significant factors associated with recent STDs in young military men. Such an index may be useful to target STD screening for those at greatest risk for STDs.