Is elimination of endemic syphilis transmission a realistic goal for the USA?
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The levels of interleukin (IL)-1, IL-6, IL-8, IL-10, and transforming growth factor-beta in sera and genital tract secretions from women with gonococcal cervicitis and other genital infections were examined. Cytokines were not elevated in genital secretions from gonococcus-infected compared with uninfected patients. The level of serum IL-6 was higher in gonococcus-infected than in uninfected patients at recruitment. Serum, but not local, IL-1 and IL-6 levels were elevated in patients concomitantly infected with Trichomonas vaginalis or Chlamydia trachomatis in addition to Neisseria gonorrhoeae compared with levels in patients infected with any single organism. Concomitant infection altered neither the total immunoglobulin concentrations nor the levels of antigonococcal antibodies in serum or local secretions. The results suggest that N. gonorrhoeae induces only a limited cytokine and antibody response during uncomplicated cervical infections; however, the presence of other sexually transmitted disease-causing organisms can alter the systemic cytokine but not the antigonococcal antibody levels.
We evaluated the willingness of clients at a large urban sexually transmitted diseases (STD) clinic in the southeastern United States to participate in future trials of preventive vaccines for HIV type 1 (HIV-1). A single trained interviewer administered an oral survey instrument to STD clinic clients over a 4-week enrollment period. The participants were 167 randomly selected clients (90 men and 77 women), most of whom were young, African-American heterosexuals. Risk behaviors for HIV-1 infection were highly prevalent. Overall, 67% of clients expressed willingness to consider participation in an HIV-1 vaccine trial. By univariate analysis, prior HIV-1 testing was significantly associated with willingness to participate (P = 0.04). Multivariate analysis revealed that female gender (P = 0.05) and prior HIV-1 testing (P = 0.03) were significant predictors of willingness to participate.
OBJECTIVE: To determine rates of compliance with doxycycline therapy for patients attending two inner city sexually transmitted diseases (STD) clinics using the MEMS (Medication Event Monitoring System) technology (Aprex Corporation, Fremont, CA). DESIGN: An observational study. SETTING: Two STD clinics in Brooklyn, New York and Birmingham, Alabama. PATIENTS: Patients warranting doxycycline as antichlamydial therapy by usual clinical criteria (e.g., documented chlamydial infections, gonococcal urethritis, mucopurulent cervicitis) were enrolled consecutively from both clinics into four separate categories according to gender and the presence or absence of symptoms: symptomatic men (77), asymptomatic men (30), symptomatic women (83), asymptomatic women (33). INTERVENTION: In the clinic area, patients were given their doxycycline in standard 30-dram medication bottles fitted with the MEMS cap, which is capable of recording the date and time of each bottle opening and closing. This information was then retrieved using a software program developed by the manufacturer. Patients were instructed to return the bottle and cap at the completion of therapy. Efforts were made to contact those who did not return their bottles by both telephone and mail. OUTCOME MEASURES: Bottle openings as recorded by the MEMS were considered to represent use of medication. Patients were considered strictly compliant with prescription instructions if bottle openings and closings occurred at least twice daily for 6 consecutive days. Noncompliance was defined as initially opening the medication more than 48 hours after leaving the clinic or opening the bottle less than once daily for 5 consecutive days. Usage between these extremes was classified as intermediate. RESULTS: Eighty percent of 223 patients enrolled completed the study by returning their bottles. The rate of strict compliance with prescription instruction was 25%. The rate of noncompliance was 24%. Fifty-one percent used some intermediate amount of medication. There was no statistical difference in compliance by gender, presence or absence of symptoms, or site of enrollment. CONCLUSIONS: Few patients administered doxycycline in an STD clinic can be expected to take medication precisely as prescribed. Although most probably take enough to eradicate uncomplicated chlamydial infections, a sizable portion can be expected to use an inadequate amount of medication. This may contribute to persistence of genital chlamydia infections in the community.
Immunoglobulin A1 (IgA1) protease, an enzyme that selectively cleaves human IgA1, may be a virulence factor for pathogenic organisms such as Neisseria gonorrhoeae. Host protection from the effects of IgA1 protease includes antibody-mediated inhibition of IgA1 protease activity, and it is believed that the relative balance between IgA1 protease and inhibitory antibodies contributes to the pathogenesis of disease caused by IgA1 protease-producing organisms. We have examined the levels of these two opposing factors in genital tract secretions and sera from women with uncomplicated infection with N. gonorrhoeae. When IgA1 in cervical mucus was examined by Western blotting, no evidence of cleavage fragments characteristic of IgA1 protease activity was seen in gonococcus-infected or control patients. Cleavage fragments typical of IgA1 protease were detected, however, after the addition of exogenous IgA1 protease to cervical mucus. Degraded IgA1 was detected in some vaginal wash samples, but the fragment pattern was not typical of IgA1 protease activity. All N. gonorrhoeae isolates from the infected patients produced IgA1 protease in vitro. All but two serum samples and 16 of 65 cervical mucus samples displayed inhibitory activity against gonococcal IgA1 protease, but there was no significant difference in the level of inhibitory activity between gonococcus-infected and noninfected patients in either cervical mucus or serum. There was no difference in the levels of IgA1 protease-inhibitory activity in serum or cervical mucus collected from patients at recruitment and 2 weeks later. These results suggest that cleavage of IgA1 by gonococcal IgA1 protease within the lumen of the female lower genital tract is unlikely to be a significant factor in the pathogenesis of infections by N. gonorrhoeae.
Chlamydia trachomatis infections are the most prevalent sexually transmitted diseases (STDs) in the United States. In acute-care settings such as clinics and emergency rooms, a desirable chlamydia screening assay should exhibit good sensitivity and good specificity and should provide test results while the patient is still present. The Biostar Chlamydia OIA (Biostar, Inc., Boulder, Colo.) is an optical immunoassay (OIA) that provides test results in less than 30 min and that uses a test format that allows office-based testing. This assay is performed entirely at room temperature without the need for rotators or other specialized equipment. The goal of this study was to compare the performance of the Biostar Chlamydia OIA for the detection of C. trachomatis with the performance of cell culture, direct fluorescent-antibody (DFA) assay (Syva MicroTrak; Syva Co., Palo Alto, Calif.), and PCR (Roche Amplicor Chlamydia trachomatis; Roche, Branchburg, N.J.) for the detection of C. trachomatis infections in women attending an urban STD clinic. For calculations of relative test performance (sensitivity, specificity, and positive and negative predictive values), patient specimens that yielded positive results by two or more of the four assays (cell culture, DFA assay, PCR, and OIA) were classified as "true infections." By these criteria, 42 of 306 total specimens were classified as positive for C. trachomatis (positive prevalence, 13.7%), 11 (3.6%; 10 by PCR and 1 by DFA assay) were positive by a single assay, and 253 (82.7%) were negative by all four tests. All culture-positive specimens were also positive by at least one other assay. Among the culture-negative specimens, 14(5%) specimens were positive by two of the three non-culture-based assays used. By using the criterion that positivity by at least two of the tests indicated a true infection,the relative sensitivities were as follows: culture and PCR, 92.9% each; Biostar Chlamydia OIA, 73.8%; and DFA assay, 59.5%.
PURPOSE: To determine utility of polymerase chain reaction (PCR)-based urine screening for Chlamydia trachomatis in the care of adolescent females in an urban clinic. METHODS: Females > or = 15 years of age attending an adolescent clinic were approached consecutively. Each enrollee was interviewed to determine the primary reason(s) for the clinic visit and was queried about genitourinary symptoms. Nonsterile voided urine specimens were tested for C. trachomatis using PCR-based analysis. Endocervical C. trachomatis cultures were obtained from the subjects who had a pelvic examination. Main outcome measures were chlamydia infection rates in clinic attendees whether a pelvic examination was performed or not. RESULTS: A total of 315 (99.4%) of 317 patients approached agreed to participate. Overall, 47 (14.9%) patients had positive urine PCR tests. The chlamydia infection rate detected by urine PCR was 22.1% (19 of 86) among those who had pelvic examinations performed and 12.2% (28 of 229) among those who did not (p = .03; odds ratio 2.04; 95% confidence interval 1.02, 4.06). Sixty percent (28 of 47) of chlamydia infections identified during the study period were identified by the urine screening test. CONCLUSION: Urine screening was accepted by vast majority of female adolescents attending the clinic irrespective of reason for the clinic visit, and was highly effective in identifying unsuspected C. trachomatis infections, particularly among girls attending the clinic for reasons unrelated to reproductive health care and as an interim screening tool for adolescent family-planning clients.
Antimicrobial susceptibilities of Neisseria gonorrhoeae have been prospectively determined in the Gonococcal Isolate Surveillance Project of the Centers for Disease Control and Prevention. From 1988 through 1994, susceptibilities were determined for 35,263 isolates from 27 clinics. Patients were demographically similar to those in nationally reported gonorrhea cases. In 1994, 30.5% of isolates had chromosomally or plasmid-mediated resistance to penicillin or tetracycline. Penicillin resistance increased from 1988 (8.4%) to 1991 (19.5%) and then decreased in 1994 (15.6%). Tetracycline resistance decreased from 1988 (23.4%) to 1989 (17.3%) and then increased in 1994 (21.7%). Most isolates (99.9%) were highly susceptible to broad-spectrum cephalosporins. Isolates with decreased susceptibility to ciprofloxacin increased from 1991 (0.4%) to 1994 (1.3%); 4 isolates were ciprofloxacin-resistant. Ciprofloxacin-resistant strains may not respond to therapy with recommended doses of fluoroquinolones, and the clinical importance of strains with decreased susceptibility is unknown. The emergence of fluoroquinolone resistance in N. gonorrhoeae in the United States threatens the future utility of this class of antimicrobials for gonorrhea therapy.
BACKGROUND AND OBJECTIVES: Patients attending sexually transmitted disease (STD) clinics are frequently screened for gonorrhea and chlamydial infection. To determine the efficiency of these screening efforts as a component of STD control, we evaluated treatment outcomes of patients with positive cultures who had not received presumptive treatment at their initial visit. GOALS: To determine the treatment outcomes of patients screened for STDs who have positive test results. STUDY DESIGN: Retrospective chart review of the computerized medical record. RESULTS: Between January 1, 1994 and June 30, 1995, 24,823 patients were tested for gonorrhea, of whom 19.3% (4791) had positive cultures. Of patients with positive gonorrhea cultures, 564 (11.8%) had positive screening cultures and did not receive therapy at the time of evaluation. Similarly, screening chlamydial cultures were positive in 1539 (10.9%) of 14,162 patients screened for chlamydial infection. Forty-four percent (677) of these did not receive presumptive treatment for chlamydial infection at their initial visit. Overall, 20% of patients with positive cultures failed to return to the clinic for treatment within 30 days of screening. Of those who did return, 30% did so only after at least 2 weeks had elapsed. CONCLUSIONS: A substantial proportion of patients with positive screening tests for gonorrhea and chlamydial infection fail to comply with follow-up recommendations and thus are likely to remain infectious. Methods must be sought to enhance patient compliance with follow-up of test results and treatment if indicated.
BACKGROUND AND OBJECTIVES: To assess the spontaneous clearance of untreated Chlamydia trachomatis infections and factors correlated with the process. STUDY DESIGN: Spontaneous clearance was assessed through review of laboratory database, chart review, and laboratory testing using direct immunofluorescence (DFA) and polymerase chain reaction (PCR) tests on C. trachomatis culture transport media from patients with negative chlamydial cultures. Specimens (C. trachomatis culture transport media) were obtained from patients attending a Birmingham, Alabama sexually transmitted diseases clinic. The study group consisted of patients with positive cultures for C. trachomatis who had repeat specimens obtained for culture within 45 days of initial observation and who had not received recommended therapy for chlamydial infection in the interval between the two tests. RESULTS: Of 74 evaluable patients, 24 (32%) had negative follow-up cultures. Culture transport media for these 24 culture-negative patients were tested with DFA or PCR assays for chlamydial infection, and 3 (13%) were positive. Culture positivity rates declined significantly with increasing age and duration of follow-up. Interval treatment with benzathine penicillin resulted in apparent resolution of infection in 9 of 10 patients. Neither a history of a C. trachomatis-associated syndrome nor treatment with cefixime, metronidazole, or antifungal agents was associated with clearance of infection. CONCLUSIONS: These results are consistent with host response-mediated resolution of infection in a minority of patients and have implications regarding public health efforts to control chlamydial infection.
OBJECTIVE: To assess patterns of self-treatment and its effects on the duration of sexually transmitted disease (STD) symptoms before medical care. METHODS: A cross-sectional interview survey in public STD clinics (7 U.S. cities). Patients, seeking treatment for STD symptoms or having a known infected sexual contact, reported self-treatment behaviors and symptom duration. Additional data were abstracted from medical charts. RESULTS: Self-treatment, primarily over-the-counter topical medications (54.8%), was reported by 21.8% of 2,508 symptomatic patients. Self-treaters were significantly more likely to be African-American (odds ratio [OR] = 1.8), female (OR = 1.7), over age 30 (OR = 1.3), report > 1 symptom (OR = 1.4), and report a genital lesion (OR = 2.1). Symptom duration was 2 days longer among self-treaters (p < 0.01). African-Americans (OR = 1.5), men (OR = 1.2), and self-treaters of symptoms other than genital lesions (OR = 1.4) had a significantly longer time from symptom onset to receiving medical care. CONCLUSIONS: Self-treatment is common among patients with STDs. Self-treatment of a genital lesion, unlike certain demographic factors and self-treatment of other STD symptoms, did not prolong the time to medical treatment.
OBJECTIVES: Although genital ulcer disease (GUD) has been associated with human immunodeficiency virus (HIV) infection in a number of studies, definitions of genital ulceration have varied. The authors hypothesized that the association of GUD with prevalent HIV infection may vary according to the definition of GUD that is used. METHODS: As part of a prospective cohort study, 863 patients were interviewed and examined who presented to a sexually transmitted disease (STD) clinic for new symptom evaluation and who agreed to HIV testing to determine demographic and behavioral risk associated with prevalent HIV infection. To determine the association between GUD and prevalent HIV, the following definitions of GUD were used: observed ulcers, history of syphilis, serologic evidence of syphilis, observed culture-proven genital herpes, and serologic evidence of herpes simplex virus type II (HSV-2) infection. RESULTS: Of 481 men and 382 women enrolled, prevalent HIV infection was detected in 12.5% and 5.2%, respectively. In multivariate analyses controlling for known HIV risk behaviors, prevalent HIV infection was associated with observed GUD (odds ratio [OR] = 2.0, 95% confidence intervals (CI) = 1.0-3.9), a history of syphilis (OR = 6.0, CI = 2.8-12.7), and serologic evidence of syphilis (OR = 3.7, CI = 1.9-7.0), but not with serologic evidence of HSV-2 (OR = 1.2, CI = 0.7-2.1), nor with observed HSV-2 culture-positive genital ulcerations (OR = 1.0, CI = 0.4-4.2). Factors contributing to different strengths of association between HIV infection and a history of syphilis or serologic evidence of syphilis included the presence of underdiagnosed syphilis infection in people with reactive serologic tests and the absence of serologic reactivity in people with a positive history. CONCLUSIONS: Although GUD is strongly associated with prevalent HIV, the strength of the association depends on the definition of GUD used. For accurate evaluation of people at risk for HIV, clinicians and researchers should use multiple definitions of GUD.
OBJECTIVE: To determine the proportion of symptomatic patients attending public sexually transmitted disease (STD) clinics who fail to seek care within 7 days of the onset of STD symptoms and their self-reported reasons for delays in obtaining care. DESIGN: Interviewers administered 23-item questionnaire to a cross section of STD clinic clients between April and September 1995. SETTING: Five urban STD clinics in the United States (Birmingham, AL; St Paul, MN; San Francisco CA; Seattle, WA; and Raleigh, NC). RESULTS: Of 1,621 patients with genitourinary symptoms, over one third (35% of men, 37% of women) presented to STD clinics only after 1 week or more of symptoms. Men with genital warts (73%) or with nongonococcal urethritis (23.1%) or symptomatic men who were recent contacts to sex partners with STDs were significantly more likely to delay clinic attendance more than a week than men with gonorrhea (6.5%, p < 0.001 for each). Overall 43.8% of women receiving specific clinical diagnoses other than genital warts delayed clinic attendance for more than 1 week. When asked why they delayed clinic attendance, respondents were most likely to respond that they had hoped their symptoms would "go away" (48.5% of men and 49.4% of women who waited a week or more before seeking care). CONCLUSION: A substantial proportion of patients with genitourinary symptoms attending public STD clinics delay seeking care for a week or more, increasing their likelihood of complications and of transmission of infection to others. Interventions to promote more timely clinic attendance may help reduce STD morbidity in the United States.
OBJECTIVES: To characterize client demographics, sexually transmitted diseases (STD) morbidity, insurance status, reasons for attending public STD clinics, and future preferences for source of STD services. DESIGN: Cross-sectional study of 2,490 clients attending five urban STD clinics for new problems with interviewer-administered 23-item questionnaire and chart review to obtain clinical and laboratory STD diagnoses. RESULTS: Participants were young (51% < 25 years of age), minority (64% nonwhite), poor (43% < or = $10,000/year), and largely uninsured (59% uninsured, 27% private insurance, and 14% Medicaid). Half had previously visited the STD clinic, and 81% had used other providers for non-STD services in the prior 3 years. STD symptoms were cited as the reason for the visit by 63%. The most common factors associated with seeking care at these STD clinics were walk-in services, costs, and confidentiality concerns. STD morbidity was high; 66% of clients were diagnosed with one or more STD. Most (68%) clients preferred to be treated at the STD clinic in the future if they could go anywhere for STD services. CONCLUSIONS: STD clinics see young, minority, poor, and uninsured clients with high STD rates. Even with unlimited future choice, two thirds of the clients surveyed would still prefer to be treated at STD clinics. This study indicates the continuing need for publicly funded, categorical STD clinics in urban areas with high STD morbidity and the importance of easily accessible, confidential, expert STD services from the private sector and managed care organizations.
In a randomized open study, 351 male patients with uncomplicated gonorrhea were given single oral doses of grepafloxacin (400 mg) or cefixime (400 mg). In the 299 microbiologically evaluable patients, urethral infections were cured in 99% (147 of 149) of those receiving grepafloxacin and 97% (145 of 150) of those given cefixime. Eradication rates for both regimens were 100% in the 16% (47 of 299) of participants who were infected with penicillin-resistant Neisseria gonorrhoeae and 97% in the 21% (62 of 299) of participants infected with tetracycline-resistant strains. Grepafloxacin is a well-tolerated alternative to cefixime for treatment of uncomplicated gonorrhea in males.
The increased sensitivities of nucleic acid amplification tests such as ligase chain reaction (LCR) have the potential to simplify specimen collection for gonorrhea diagnosis. In this study patients took their own vaginal swab specimens for gonorrhea culture and LCR testing. Immediately following specimen collection by patients, a trained clinician obtained endocervical swab specimens for the same tests. By using LCR to diagnose gonorrhea, 54 (17.5%) of 309 patients had positive tests. Forty-five patients with positive cervical LCR tests also had positive vaginal LCR tests; for one patient, only a cervical LCR specimen was positive, and for eight patients, only vaginal specimens were positive. For specimens from patients whose gonorrhea cultures were positive, all vaginal swab specimens were positive by LCR and 42 (91%) of 46 cervical swab specimens were positive by LCR. LCR-positive specimens from eight patients with negative cultures (four with positive vaginal specimens only, one with a positive cervical specimen only, and three with positive vaginal and cervical specimens) were further evaluated with unrelated probe sets for gonococcal pilin B. Following resolution of the discrepancies between culture-negative and LCR-positive specimens, a diagnosis of gonorrhea could be confirmed for 52 of 54 patients with positive LCR tests. LCR testing with vaginal swabs was 100% sensitive and 99.6% specific and had a positive predictive value of 98.1% and a negative predictive value of 100%. In this study LCR testing of vaginal swab specimens obtained by patients themselves was significantly more sensitive for gonorrhea diagnosis of women than cervical LCR or culture (100% versus 84.6% for cervical LCR or culture; Mantel-Haenszel chi-square test result, 8.58; P = 0.003).
We compared the ligase chain reaction (LCR) assay to cell culture for diagnosis of genitourinary chlamydial infections in women using swab specimens obtained by clinicians from the endocervix and by patients from their own vaginas. Specimens from 40 (12.9%) of 309 patients were positive for chlamydial infection by culture, while the specimens of 50 (16.2%) patients were positive by LCR. Chlamydia trachomatis infection was verified for 9 of 10 patients whose LCR specimens were positive but whose cultures were negative. Vaginal and cervical swab specimens were positive by LCR for 46 (93.9%) and 44 (89.8%) of 49 chlamydia-infected patients, respectively. These data suggest that LCR testing for chlamydia with vaginal swab specimens obtained by patients themselves is as sensitive as cervical LCR and more sensitive than cell culture.
Al Jonson pointed out that Sir William Osler provided one of the best rationales for Humanities in Medicine (21, 65). In 1919, in one of Sir William's last lectures given just a few months prior to his death, a lecture to the British Classical Society, he discussed how the sciences and the humanities can inform each other. He compared the humanities to thyroid hormone-thyroxine had just been discovered in 1914-"a hormone...," Sir William said, "...which lubricates the wheels of life... Deprive man of the lubricants ... and ... he sinks into dementia..." And so to the Classical Society, Sir William said, "You secrete materials which do for society at large what the thyroid gland does for the individual. The humanities are the hormones..." And Al Jonsen suggested that we in Medicine reaffirm Sir William's metaphor that the humanities are the hormones which will do for medicine what they do for society at large.