Use of cell culture and a rapid diagnostic assay for Chlamydia trachomatis screening.

OBJECTIVE: To compare a rapid, office-based test with standard cell culture for screening of women for Chlamydia trachomatis infections. DESIGN AND SETTINGS: An 8-month prospective crossover trial used alternating screening protocols in two Baltimore (Md) sexually transmitted disease clinics from January 2 through August 14, 1991. PARTICIPANTS: Consecutive women attending the two clinics who had no indication for administration of antichlamydial antibiotic therapy (eg, history of recent sexual contact with a partner with a sexually transmitted disease, mucopurulent cervicitis, pelvic inflammatory disease, known gonorrhea, or previously diagnosed Chlamydia infections). INTERVENTIONS: Chlamydia screening was offered according to one of two protocols. Use of the two screening protocols was alternated between clinics each month. In the "rapid test clinic," eligible women were screened with both a 30-minute enzyme immunoassay test and tissue culture. Patients screened with the rapid test were asked to remain in the clinic until their rapid assay results were available so that, if positive, the patients could be treated. In the "routine screening clinic," eligible women were screened for Chlamydia by cell culture. Women identified as being infected with Chlamydia by screening culture were later confidentially notified of their test results by health department disease intervention specialists and referred for therapy. MAIN OUTCOME MEASURES: Performance of screening tests for bringing infected patients to therapy; time intervals between initial clinic visits and therapy; and pelvic inflammatory disease occurring between initial visits and therapy. RESULTS: Chlamydia cultures were positive in 100 (6.6%) of 1526 women screened with the solid-phase immunoassay, 47 of which were detected and treated on the basis of rapid test results. In contrast, 93 (74%) of 126 women with positive screening cultures returned to the clinic and received therapy. The median interval between testing and therapy for women with positive screening cultures was 14 days, and three (3.2%) developed pelvic inflammatory disease in the interval between testing and return for therapy. CONCLUSIONS: Neither cell culture nor a rapid diagnostic test performed well for ensuring therapy of women with Chlamydia infections. The sensitivity of the rapid diagnostic test was low, and nearly one fourth of the women with positive screening cultures did not return for therapy. Evaluation of screening for Chlamydia should consider the utility of strategies for bringing patients to treatment, as well as the more usual measures of test performance, such as sensitivity, specificity, and predictive values.

Comparative behavioral epidemiology of gonococcal and chlamydial infections among patients attending a Baltimore, Maryland, sexually transmitted disease clinic.

Between April 1988 and May 1989, 400 males and 400 females attending a Baltimore, Maryland, sexually transmitted disease clinic were enrolled in a study evaluating and comparing behaviors associated with culture-proven gonococcal or chlamydial infection. The subjects were enrolled consecutively, and were all seen by the same clinician. Among participants of each sex, gonorrhea but not chlamydia was associated with increasing numbers of recent (the past 30 days) sexual partners. Compared with males with neither infection, factors independently associated with increased risk of gonorrhea included age less than 20 years (odds ratio (OR) = 1.93), the presence of genitourinary symptoms (OR = 8.07), and recent exposure to a new sexual partner (OR = 2.78); risk for chlamydial infection in males was associated with genitourinary symptoms (OR = 2.83) and was significantly reduced in those reporting multiple recent (OR = 0.19) or new (OR = 0.07) sexual partners. Among females, age less than 20 years was independently associated with gonococcal (OR = 1.86) and chlamydial (OR = 7.79) infections in comparison with females with neither infection. No other behavioral factors were associated with chlamydial infection for females in this study; however, having a regular sexual partner was associated with significantly elevated risk of gonorrhea (OR = 3.85), while the presence of genital tract symptoms was associated with diminished risk (OR = 0.29) for gonorrhea. These data suggest that there are differences in the behaviors associated with gonorrheal and chlamydial infections and that different strategies may be useful in efforts to control these infections.

Temporal trends in gonococcal antibiotic resistance in Baltimore.

Each month from August 1986 through July 1990, clinical and laboratory data were evaluated for the first 25 urethral isolates of Neisseria gonorrhoeae from men attending a Baltimore sexually transmitted disease (STD) clinic as part of an effort to understand factors that contribute to changes in gonococcal antimicrobial susceptibility. During the 48-month study period, 1193 gonococcal isolates were evaluated; the proportion of penicillinase-producing N. gonorrhoeae (PPNG) isolates steadily increased, the prevalence of tetracycline-resistant N. gonorrhoeae (TRNG) remained relatively stable, and chromosomally mediated penicillin resistance increased steadily during the first 5 6-month intervals, then decreased, only to increase again during the final 2 6-month intervals. Changes in antibiotic treatment regimens for gonorrhea were associated with changes in the prevalence of chromosomally mediated penicillin resistance. In a supplementary study to characterize patterns of antibiotic use among men and women attending the STD clinics, 9% of patients reported antibiotic use in the 2 weeks prior to clinic visit. Antibiotics were taken prior to clinic attendance by 65% of patients reporting antibiotic use, because of concerns regarding possible STD or STD exposure. These patients were significantly less likely to be culture positive for N. gonorrhoeae when compared with patients who did not report antibiotic use. Temporal trends in N. gonorrhoeae antibiotic resistance appear to be influenced by many factors, including treatment regimens and self medication.

Disease prevalence among women attending a sexually transmitted disease clinic varies with reason for visit.

Prevalence of sexually transmitted diseases (STD) and selected behavioral and demographic variables were evaluated in 279 women attending a Baltimore STD clinic, using a standardized questionnaire and cultures for Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis. Stratified by reason for clinic visit, 102 (37%) of 279 women attending the clinic stated that they were recent contacts to men with STDs with the majority (59 out of 102, or 58%) reporting gonorrhea contact as their reason for visit. Another 124 women (44%) came to the clinic for symptom evaluation, and 53 (19%) for other reasons. Prevalence of STDs was higher among those attending as contacts than among noncontacts: 35% versus 15% for N. gonorrhoeae; 26% versus 16% for C. trachomatis; and 27% versus 15% for T. vaginalis (P less than 0.05 for each). Furthermore, multiple infections were found in 23% of those attending as contacts but only in 10% of noncontacts (P less than 0.001). In general, patients reporting contact with an infected person were also less likely to report symptoms (43% versus 34%, P less than 0.001), despite increased disease prevalence. These data suggest that multiple STDs are often present in women attending STD clinics, irrespective of reason for visit. Merely treating women for reported exposure without further evaluation will fail to identify a substantial number of women coinfected with other organisms.

Effect of HIV posttest counseling on STD incidence.

OBJECTIVE: To evaluate the effectiveness of human immunodeficiency virus (HIV) testing and posttest counseling in reducing subsequent high-risk behavior. METHODS: The incidence of sexually transmitted diseases (STDs) in the Baltimore, Md, public STD clinic population after HIV testing and counseling was determined by chart review and was compared in two groups, 868 HIV-seropositive patients and 1104 HIV-seronegative patients, matched by age, sex, and month in which HIV test was conducted. Patients were observed for incident STDs at intervals of 6 through 23 months. Patients with incident STDs were classified hierarchically after being notified of the HIV test result and receiving posttest counseling. RESULTS: Of HIV-seropositive patients, 615 (71%) returned for their test results and received posttest counseling; 694 HIV-seronegative patients (63%) returned. Of all those who returned for results and posttest counseling, 60 (9.7%) of 615 HIV-seropositive patients and 61 (8.8%) of 694 HIV-seronegative patients were diagnosed at least once with definite STD (syphilis, gonorrhea, or trichomoniasis) (P, not significant). Twenty-four HIV-seropositive patients (3.9%) and 71 HIV-seronegative patients (10.2%) returned with probable STD (nongonococcal urethritis or pelvic inflammatory disease) (P less than .001). Nine HIV-seropositive patients (1.5%) and 23 HIV-seronegative patients (3.3%) returned having had an STD-infected sexual partner (P less than .03). Age, sexual orientation, and drug use behavior did not predict return with STD. CONCLUSIONS: Both HIV-seropositive and HIV-seronegative patients showed high rates of repeat STDs after posttest counseling, an important public health challenge in creating effective high-risk behavior prevention strategies.

A comparison of single-dose cefixime with ceftriaxone as treatment for uncomplicated gonorrhea. The Gonorrhea Treatment Study Group.

BACKGROUND: Because of the widespread existence of Neisseria gonorrhoeae resistant to penicillin or tetracycline, ceftriaxone is now recommended for the treatment of gonorrhea. There is, however, a need for effective antibiotics that can be administered orally as an alternative to ceftriaxone, which requires intramuscular administration. Cefixime is an orally absorbed cephalosporin that is active against resistant gonococci and has pharmacokinetic activity suitable for single-dose administration. METHODS AND RESULTS: In a randomized, unblinded multicenter study of 209 men and 124 women with uncomplicated gonorrhea, we compared three single-dose treatment regimens: 400 mg or 800 mg of cefixime, administered orally, and 250 mg of ceftriaxone administered intramuscularly. The overall cure rates were 96 percent for the 400-mg dose of cefixime (89 of 93 patients) (95 percent confidence interval, 93.5 percent to 97.8 percent); 98 percent for the 800-mg dose of cefixime (86 of 88 patients) (95 percent confidence interval, 94.6 percent to 100 percent); and 98 percent for ceftriaxone (92 of 94 patients) (95 percent confidence interval, 94.9 to 100 percent). The cure rates were similar in men and women, and pharyngeal infection was eradicated in 20 of 22 patients (91 percent). Thirty-nine percent of 303 pretreatment gonococcal isolates had one or more types of antimicrobial resistance; the efficacy of all three regimens was independent of the resistance pattern. Chlamydia trachomatis infection persisted in at least half the patients infected in each treatment group. All three regimens were well tolerated. CONCLUSIONS: In the treatment of uncomplicated gonorrhea, a single dose of cefixime (400 or 800 mg) given orally appears to be as effective as the currently recommended regimen of ceftriaxone (250 mg given intramuscularly).

CD4 lymphocyte concentrations in patients with newly identified HIV infection attending STD clinics. Potential impact on publicly funded health care resources.

Since January 1990, human immunodeficiency virus (HIV)-infected patients attending two sexually transmitted disease clinics in Baltimore, Md, have been offered T-lymphocyte subset evaluations. From January through September, CD4+ lymphocyte concentrations were measured in 223 newly diagnosed HIV-infected patients; 50% had fewer than 500 CD4+ T cells and 12% had fewer than 200 CD4+ T cells per cubic millimeter. Most patients were asymptomatic, and, even among patients with fewer than 200 CD4+ T cells, 54% had no symptoms or signs suggestive of advanced HIV infection. Homosexually active men had significantly lower mean CD4+ lymphocyte concentrations than intravenous drug users. Given the substantial numbers of patients with CD4+ concentrations that qualified them for zidovudine therapy, we also assessed their mechanisms of paying for health care. Only 24% of HIV-infected patients had private insurance. Seventy-two percent of patients with fewer than 200 CD4+ T cells either had no insurance or relied on public assistance for health care. Thus, although 50% of asymptomatic individuals identified by routine voluntary HIV screening in an inner-city sexually transmitted disease clinic may benefit from therapy for their disease, 75% of those qualifying for presently recommended therapy either depend on publicly funded health care or have no means of payment for care.

Cocaine hydrochloride and benzoylecgonine have no in vitro inhibitory effect against Neisseria gonorrhoeae.

We evaluated 72 clinical Neisseria gonorrhoeae isolates for in vitro susceptibility to cocaine hydrochloride and its metabolite benzoylecgonine and to penicillin, tetracycline, erythromycin, ceftriaxone, and ofloxacin. Although there was a wide range of susceptibilities to the antimicrobial agents, cocaine and its major metabolite, benzoylecgonine, had no demonstrable antigonococcal activity. Cocaine use is frequently associated with outbreaks of sexually transmitted disease. We hypothesized that the dramatically decreasing incidence of gonorrhea over the past 15 years may be in part due to pharmacological effects of cocaine. However, since cocaine and its metabolite have no in vitro antigonococcal activity, this hypothesis is unlikely.

Characteristics of patients with syphilis attending Baltimore STD clinics. Multiple high-risk subgroups and interactions with human immunodeficiency virus infection.

Medical records of 341 patients with syphilis seen at a health department sexually transmitted disease clinic were reviewed to assess membership in high-risk subgroups and interactions with human immunodeficiency virus (HIV) infection. When compared with the entire clinic population, patients with syphilis tended to be older and were more likely to acknowledge intravenous drug use, more often had a history of syphilis, and, among men, were more often homosexually active. Half of the men with syphilis and one third of the women fell into one or more of these high-risk subgroups. Patients with syphilis were also more likely to test positive for HIV infection than other patients attending the clinic. Patients admitting to intravenous drug use, prior syphilis, or being homosexually active were significantly more likely to be HIV seropositive than patients without these characteristics, even though patients with these characteristics were significantly more likely to refuse HIV serologic testing. Although clinical stage of syphilis at presentation did not differ when patients with and without concurrent HIV infection were compared, geometric mean rapid plasma reagin titers were significantly higher in HIV-infected patients with secondary syphilis.

Evaluation of Abbott Testpack Chlamydia for detection of Chlamydia trachomatis in patients attending sexually transmitted diseases clinics.

This work compares a rapid solid-phase EIA (Abbott TestPack Chlamydia) to tissue culture and a direct fluorescent antibody test (Syva Microtrak) for detection of C. trachomatis in 436 patients attending two inner-city sexually transmitted diseases (STD) clinics. The prevalence of C. trachomatis by culture was 12% (5% in men, 15% in women). Overall sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of TestPack compared to culture were 70%, 98%, 80%, and 96% respectively. In men, 12 specimens were positive by TestPack, while only eight specimens were positive by culture. Six TestPack-positive, culture-negative specimens were further evaluated by centrifugation of culture transport media and examination of the sediment for chlamydia elementary bodies (EBs) using fluorescent monoclonal antibodies to C. trachomatis. Using this procedure, five of six culture negative specimens contained EBs (revised sensitivity 85%, specificity 99%, PPV 92%, NPV 99%). In 285 women evaluable in culture and TestPack, 44 (15%) specimens were culture positive; TestPack was positive in 29 (sensitivity 66%) culture positive women. Of 241 culture negative patients, 238 had negative TestPack results (specificity 99%) and no EBs were detected in the culture-negative, TestPack-positive specimens. Twenty-three (8%) Microtrak specimens were unsatisfactory for testing; two of these were culture and TestPack positive. Therefore, of 263 specimens evaluable using Microtrak, 42 (16%) specimens were culture positive; Microtrak was positive in 32 (sensitivity 76%) culture-positive women. Abbott TestPack Chlamydia is a rapid (25 minute), visually read format requiring no specialized equipment for detection of chalmydia infections with a sensitivity comparable to that of Microtrak.

Evaluation of Syva enzyme immunoassay for detection of Chlamydia trachomatis in genital specimens.

Detection of Chlamydia trachomatis infection was evaluated by culture and a new Syva enzyme immunoassay (EIA) in 1,012 patients at two Baltimore, Md., sexually transmitted disease clinics. The overall chlamydia prevalence determined by culture was 12%. For 506 fresh cervical and urethral specimens, the sensitivity of Syva EIA was 90% and its specificity was 94% compared with culture. Discordant Syva EIA results were further evaluated by staining the sediment in centrifuged culture transport media and Syva EIA transport tubes with a fluorescent monoclonal antibody to C. trachomatis to detect elementary bodies. Reanalysis of the data after use of this technique to resolve discordant results increased sensitivity and specificity to 92 and 96%, respectively. A subsample of 307 fresh cervical specimens was also tested in a three-way comparison using Abbott Chlamydiazyme, Syva EIA, and culture. In this sample, compared with culture, the sensitivity and specificity of Syva EIA were 87 and 95%, respectively, and for Chlamydiazyme they were 77 and 98%, respectively. Syva EIA is a 4-h, easy-to-perform enzyme-linked immunosorbent assay which has a high sensitivity with fresh genital specimens and offers an excellent alternative to culture.

Behavioral contributions to acquisition of gonorrhea in patients attending an inner city sexually transmitted disease clinic.

To begin to define the behaviors that influence gonorrhea acquisition, a case-series of patients attending a sexually transmitted disease clinic was surveyed. Although gonorrhea rates were similar, men and women differed in sexual behaviors predictive of infection. Men with a new or casual partner were more likely to have gonorrhea than men with no such partners (adjusted odds ratio = 2.7); this finding did not hold true for women. Condom use in the previous month reduced the chances of gonorrhea acquisition for both men and women. More than 33% continued to engage in sexual activity after onset of symptoms or knowledge of sexually transmitted disease exposure. Individuals with repeated episodes of gonorrhea exhibited an array of risk-taking behaviors, such as intravenous drug use and casual sex partners. These data suggest the complex nature of the behaviors and sexual contexts within which gonorrhea acquisition occurs.

Comparison of GC-Lect and modified Thayer-Martin media for isolation of Neisseria gonorrhoeae.

A new selective medium, GC-Lect, was compared with modified Thayer-Martin medium (MTM) for isolation of Neisseria gonorrhoeae. Cultures from 620 sexually transmitted disease clinic patients were directly inoculated onto both media, placed in candle extinction jars, and incubated. N. gonorrhoeae was isolated from 175 (29%) of 607 genital cultures, 3 (3%) of 88 pharyngeal cultures, and 6 (29%) of 21 rectal cultures. Ten cultures were positive only on GC-Lect, and 3 were positive only on MTM. In 3 of the 10 cultures positive only on GC-Lect, overgrowth of a Capnocytophaga sp. may have obscured growth on MTM. In this study, vancomycin-susceptible (MIC, less than 4.0 micrograms/ml) N. gonorrhoeae was isolated on both media, and none of the isolates missed by either medium were susceptible to vancomycin. No differences were noted between the two media in time required for isolation of N. gonorrhoeae. While isolation rates of N. gonorrhoeae were similar, suppression of nongonococcal bacterial species by GC-Lect was superior to that by MTM. GC-Lect is equal to MTM for detection of N. gonorrhoeae and is superior for suppression of normal flora.

Determinants of emergence of antibiotic-resistant Neisseria gonorrhoeae.

Studies were carried out to evaluate the prevalence and risk factors for antibiotic-resistant Neisseria gonorrhoeae infections. Monthly surveillance of gonococcal isolates showed the prevalence of gonococci with high-level, plasmid-mediated tetracycline resistance (TRNG) to be about 15% for three consecutive 6-mo periods. Over the same period, the prevalence of gonococci with chromosomally mediated resistance to penicillin G steadily increased, from 0% to 9% and then to 21%. From April to July 1987, while chromosomally mediated penicillin resistance was rapidly increasing, a more intensive study was conducted. Patients infected with TRNG reported significantly more lifetime sexual partners (P less than .05) but otherwise resembled patients infected with antibiotic-sensitive gonococci. Patients infected with chromosomally mediated penicillin-resistant gonococci differed from other patients. In addition to reporting more lifetime partners (P less than .05), patients with chromosomally mediated penicillin-resistant gonorrhea were more likely to be older (P less than .05) and more often reported past episodes of gonorrhea (P less than .05), greater numbers of recent sexual partners (P less than .05), new sexual partners (P less than .05), prostitute contact (P = .06), and parenteral drug use or sexual partners who were drug users (P = .07). The introduction of antibiotic-resistant N. gonorrhoeae into communities may be attributable to a subset of patients who practice "risky behaviors" and who could be targeted for disease intervention activities.