H. Hunter Handsfield

Invasion of the Central Nervous System by Treponema pallidum: Implications for Diagnosis and Treatment

STUDY OBJECTIVES To determine the prevalence of Treponema pallidum in cerebrospinal fluid (CSF) of patients with syphilis, to determine the effect of concurrent HIV infection on central nervous system involvement by T. pallidum, and to examine the efficacy of conventional therapy for asymptomatic neurologic involvement. PATIENTS Fifty-eight patients with untreated syphilis who consented to lumbar puncture, representing approximately 10% of new cases of syphilis during the study period. INTERVENTIONS Lumbar puncture was done on all patients. Rabbit inoculation was used to test cerebrospinal fluid for viable T. pallidum. Patients with normal fluid received recommended benzathine penicillin therapy according to the stage of syphilis; patients with CSF abnormalities were offered 10-day therapy for neurosyphilis. RESULTS Treponema pallidum was isolated from the CSF of 12 (30%) of 40 patients (95% CI, 17 to 46) with untreated primary and secondary syphilis; isolation of T. pallidum was significantly associated (P = 0.008) with the presence of two or more abnormal laboratory variables (among leukocyte count, protein concentration, and CSF-Venereal Disease Research Laboratory [VDRL] test). Two (67%) of 3 early latent (CI, 13 to 100) and 3 (20%) of 15 late latent syphilis patients (CI, 5 to 47) also had reactive CSF-VDRL tests and elevated cell and protein levels, although T. pallidum was not isolated. Concurrent infection with the human immunodeficiency virus (HIV) was not associated with isolation of T. pallidum, increased number of CSF abnormalities, or reactive CSF serologic tests for syphilis, although CSF pleocytosis was commoner in subjects infected with HIV. Treatment with conventional benzathine penicillin G (2.4 mIU) failed to cure 3 of 4 patients with secondary syphilis from whom T. pallidum was isolated before therapy; all 3 patients in whom treatment failed were HIV seropositive when treated or seroconverted during follow-up. CONCLUSIONS Central nervous system invasion by T. pallidum is common in early syphilis, and is apparently independent of HIV infection. Examination of the CSF may be beneficial in patients with early syphilis, and therapy should be guided by knowledge of central nervous system involvement. Conventional benzathine penicillin G therapy may have reduced efficacy in patients with early syphilis who are also infected with HIV.

Etiology of Nongonococcal Urethritis

Chlamydia trachomatis was isolated from the urethra from 48 (42 per cent) of 113 men with non-gonococcal urethritis (NGU), four (7 per cent) of 58 without overt urethritis, and 13 (19 per cent) of 69 with gonorrhea. Postgonococcal urethritis (PGU) developed in 11 of 11 men who had C. trum antibody to C. trachomatisis developed. The immunotype specificity of chlamydial antibody corresponded to the immunotype isolated. Among culture-negative patients. chlamydial antibody prevalence correlated with the number of past sex partners and with previous NGU. Herpesvirus hominis, cytomegalovirus, T-mycoplasma, Mycoplasma hominis, other bacteria, and Trichomonas vaginalis were not implicated in NGU or PGU. Thus, the cause of chlamydia-negative NGU and PGU remains obscure. Endocervical chlamydia were found in sex partners of 15 of 22 NGU patients with and two of 24 without urethral chlamydial infection (p smaller than 0.001). Tetracycline treatment of both sex partners appears advisable.

Culture-Independent Diagnosis of Chlamydia trachomatis Using Monoclonal Antibodies

To simplify the diagnosis of chlamydial genital infection, we used a fluorescein-conjugated monoclonal antibody in immunofluorescence tests on smears prepared from urethral or cervical secretions obtained directly from patients. This direct test, requiring less than 30 minutes to perform, was based on the detection of extracellular chlamydial elementary bodies. A comparison of the direct test with cultures stained with iodine on specimens from 926 patients demonstrated a sensitivity of 93 per cent and a specificity of 96 per cent. The direct test provides a rapid, simple, and sensitive method for the diagnosis of chlamydial infection, which can be performed in laboratories that do not have tissue-culture capability.

Sexual mixing patterns in the spread of gonococcal and chlamydial infections.

OBJECTIVES This study sought to define, among sexually transmitted disease (STD) clinic attendees, (1) patterns of sex partner selection, (2) relative risks for gonococcal or chlamydial infection associated with each mixing pattern, and (3) selected links and potential and actual bridge populations. METHODS Mixing matrices were computed based on characteristics of the study participants and their partners. Risk of infection was determined in study participants with various types of partners, and odds ratios were used to estimate relative risk of infection for discordant vs concordant partnerships. RESULTS Partnerships discordant in terms of race/ethnicity, age, education, and number of partners were associated with significant risk for gonorrhea and chlamydial infection. In low-prevalence subpopulations, within-subpopulation mixing was associated with chlamydial infection, and direct links with high-prevalence subpopulations were associated with gonorrhea. CONCLUSIONS Mixing patterns influence the risk of specific infections, and they should be included in risk assessments for individuals and in the design of screening, health education, and partner notification strategies for populations.

Patient-delivered partner treatment with azithromycin to prevent repeated Chlamydia trachomatis infection among women: A randomized, controlled trial

Background Repeated infection with Chlamydia trachomatis increases the risk for serious sequelae: pelvic inflammatory disease, ectopic pregnancy, infertility, and chronic pelvic pain. A substantial proportion of women treated for C trachomatis infection are reinfected by an untreated male sex partner in the first several months after treatment. Effective strategies to ensure partner treatment are needed. Goal The goal of the study was to determine whether repeated infections with C trachomatis can be reduced by giving women doses of azithromycin to deliver to male sex partners. Study Design A multicenter randomized controlled trial was conducted among 1787 women aged 14 to 34 years with uncomplicated C trachomatis genital infection diagnosed at family planning, adolescent, sexually transmitted disease, and primary care clinics or emergency or other hospital departments in five US cities. Women treated for infection were randomized to one of two groups: patient-delivered partner treatment (in which they were given a dose of azithromycin to deliver to each sex partner) or self-referral (in which they were asked to refer their sex partners for treatment). The main outcome measure was C trachomatis DNA detected by urine ligase chain reaction (LCR) or polymerase chain reaction (PCR) by 4 months after treatment. Results The characteristics of study participants enrolled in each arm were similar except for a small difference in the age distribution. Risk of reinfection was 20% lower among women in the patient-delivered partner treatment arm (87/728; 12%) than among those in the self-referral arm (106/726; 15%); however, this difference was not statistically significant (odds ratio, 0.80; 95% confidence interval, 0.62–1.05;P = 0.102). Women in the patient-delivered partner treatment arm reported high compliance with the intervention (82%). Conclusion Patient-delivered partner treatment for prevention of repeated C trachomatis infection among women is comparable to self-referral and may be an appropriate option for some patients.

Asymptomatic gonorrhea in men. Diagnosis, natural course, prevalence and significance.

Abstract Urethral gonococcal infection was detected in 40 per cent of asymptomatic male contacts of women with symptomatic gonorrhea. Culture was more sensitive than fluorescent antibody or Gram-stained smears in detecting asymptomatic genital infection in men, and Neisseria gonorrhoeae was detected more often in the anterior urethra than in prostatic secretions by all three methods. Among 28 asymptomatically infected men followed without treatment for seven to 165 days, 18 remained asymptomatic carriers of N. gonorrhoeae. N. gonorrhoeae was cultured from 59 (2.2 per cent) of 2628 sexually active United States Army enlisted men undergoing routine examinations, and 68 per cent of the infected men were asymptomatic. Asymptomatically infected men constitute a definite reservoir of N. gonorrhoeae, and a major factor in the current gonorrhea pandemic is the failure of physicians to identify and treat asymptomatic male contacts of women with gonorrhea that is either symptomatic or detected by routine culturing....

PERFORMANCE AND COST-EFFECTIVENESS OF SELECTIVE SCREENING CRITERIA FOR CHLAMYDIA TRACHOMATIS INFECTION IN WOMEN. IMPLICATIONS FOR A NATIONAL CHLAMYDIA CONTROL STRATEGY

Background and Objectives: Detection of subclinical Chlamydia trachomatis infection in women is a high but costly public health priority. Goals: To develop and test simple selective screening criteria for chlamydia in women, to assess the contribution of cervicitis to screening criteria, and to evaluate cost‐effectiveness of selective versus universal screening. Study Design: Cross‐sectional study and cost‐effectiveness analysis of 11,141 family planning (FP) and 19,884 sexually transmitted diseases (STD) female clients in Washington, Oregon, Alaska, and Idaho who were universally tested for chlamydia using cell culture, direct fluorescent antibody, enzyme immunoassay, or DNA probe. Results: Prevalence of cervical chlamydial infection was 6.6%. Age younger than 20 years, signs of cervicitis, and report of new sex partner, two or more partners, or symptomatic partner were independent predictors of infection. Selective screening criteria consisting of age 20 years or younger or any partner‐related risk detected 74% of infections in FP clients and 94% in STD clients, and required testing 53% of FP and 77% of STD clients. Including cervicitis in the screening criteria did not substantially improve their performance. Universal screening was more cost‐effective than selective screening at chlamydia prevalences greater than 3.1% in FP clients and greater than 7% in STD clients. Conclusions: Age and behavioral history are as sensitive in predicting chlamydial infection as criteria that include cervicitis. Cost‐effectiveness of selective screening is strongly influenced by the criterias sensitivity in predicting infection, which was significantly higher in STD clients. At the chlamydia prevalences in the populations studied, it would be cost saving to screen universally in FP clinics and selectively in STD clinics, the reverse of current practice in many locales.

Antibody to human immunodeficiency virus (HIV) and suboptimal response to hepatitis B vaccination

STUDY OBJECTIVE To analyze the relation between human immunodeficiency virus (HIV) infection and the antibody response to plasma-derived hepatitis B vaccine. DESIGN Open-label longitudinal cohort study; blinded laboratory studies. SETTING University-affiliated municipal hospital. PATIENTS Homosexually active men with negative assays for hepatitis B surface antigen (HBsAg), hepatitis B core antigen, and antibody to HBsAg; recruited in a sexually transmitted disease clinic or referred from community practitioners. INTERVENTIONS Immunization with 20 micrograms of plasma-derived hepatitis B virus vaccine intramuscularly, repeated after 1 and 6 months; standardized evaluation at entry and at 1, 2, 6, and 7 months. MEASUREMENTS AND MAIN RESULTS Low antibody response or nonresponse to vaccination occurred in 7 of 16 HIV-seropositive patients, compared with 6 of 68 HIV-seronegative patients (P = 0.002). Median levels of antibody to HBsAg 7 months after the first vaccine dose were 205.3 sample ratio units for HIV-seronegative patients and 15.5 sample ratio units for HIV-seropositive patients. By multivariate analysis, vaccine response was associated with HIV antibody status and not with cytomegalovirus infection, lymphocyte subset results, or impaired cutaneous delayed hypersensitivity. CONCLUSIONS Infection with HIV is associated with suboptimal antibody response to plasma-derived hepatitis B virus vaccine. Determination of antibody levels after vaccination in HIV-seropositive patients may be warranted.

Determinants of persistent and recurrent Chlamydia trachomatis infection in young women: results of a multicenter cohort study.

Background Sequelae of genital Chlamydia trachomatis infection in women are more strongly linked to repeat infections than to initial ones, and persistent or subsequent infections foster continued transmission. Objective To identify factors associated with persistent and recurrent chlamydial infection in young women that might influence prevention strategies. Methods Teenage and young adult women with uncomplicated C trachomatis infection attending reproductive health, sexually transmitted disease, and adolescent medicine clinics in five US cities were recruited to a cohort study. Persistent or recurrent chlamydial infection was detected by ligase chain reaction (LCR) testing of urine 1 month and 4 months after treatment. Results Among 1,194 women treated for chlamydial infection, 792 (66.4%) returned for the first follow-up visit , 50 (6.3%) of whom had positive LCR results. At that visit, women who resumed sex since treatment were more likely to have chlamydial infection (relative risk [RR], 2.0; 95% CI, 1.03–3.9), as were those who did not complete treatment (RR, 3.4; 95% CI, 1.6–7.3). Among women who tested negative for C trachomatis at the first follow-up visit, 36 (7.1%) of 505 had positive results by LCR at the second follow-up visit. Reinfection at this visit was not clearly associated with having a new sex partner or other sexual behavior risks; new infection was likely due to resumption of sex with untreated partners. Overall, 13.4% of women had persistent infection or became reinfected after a median of 4.3 months, a rate of 33 infections per 1,000 person months. Conclusions Persistent or recurrent infection is very common in young women with chlamydial infection. Improved strategies are needed to assure treatment of women’s male sex partners. Rescreening, or retesting of women for chlamydial infection a few months after treatment, also is recommended as a routine chlamydia prevention strategy.

A comparison between audio computer-assisted self-interviews and clinician interviews for obtaining the sexual history.

Objective: The objective of this study was to compare reporting between audio computer-assisted self-interview (ACASI) and clinician-administered sexual histories. Goal: The goal of this study was to explore the usefulness of ACASI in sexually transmitted disease (STD) clinics. Study: The authors conducted a cross-sectional study of ACASI followed by a clinician history (CH) among 609 patients (52% male, 59% white) in an urban, public STD clinic. We assessed completeness of data, item prevalence, and report concordance for sexual history and patient characteristic variables classified as socially neutral (n = 5), sensitive (n = 11), or rewarded (n = 4). Results: Women more often reported by ACASI than during CH same-sex behavior (19.6% vs. 11.5%), oral sex (67.3% vs. 50.0%), transactional sex (20.7% vs. 9.8%), and amphetamine use (4.9% vs. 0.7%) but were less likely to report STD symptoms (55.4% vs. 63.7%; all McNemar chi-squared P values <0.003). Men’s reporting was similar between interviews, except for ever having had sex with another man (36.9% ACASI vs. 28.7% CH, P <0.001). Reporting agreement as measured by kappas and intraclass correlation coefficients was only moderate for socially sensitive and rewarded variables but was substantial or almost perfect for socially neutral variables. ACASI data tended to be more complete. ACASI was acceptable to 89% of participants. Conclusions: ACASI sexual histories may help to identify persons at risk for STDs.