Mary L. Kamb

Global Estimates of Syphilis in Pregnancy and Associated Adverse Outcomes: Analysis of Multinational Antenatal Surveillance Data

Using multinational surveillance data, Lori Newman and colleagues estimate global rates of active syphilis in pregnant women, adverse effects, and antenatal coverage and treatment needed to meet WHO goals.

Untreated maternal syphilis and adverse outcomes of pregnancy: a systematic review and meta-analysis

OBJECTIVE To perform a systematic review and meta-analysis of reported estimates of adverse pregnancy outcomes among untreated women with syphilis and women without syphilis. METHODS PubMed, EMBASE and Cochrane Libraries were searched for literature assessing adverse pregnancy outcomes among untreated women with seroreactivity for Treponema pallidum infection and non-seroreactive women. Adverse pregnancy outcomes were fetal loss or stillbirth, neonatal death, prematurity or low birth weight, clinical evidence of syphilis and infant death. Random-effects meta-analyses were used to calculate pooled estimates of adverse pregnancy outcomes and, where appropriate, heterogeneity was explored in group-specific analyses. FINDINGS Of the 3258 citations identified, only six, all case-control studies, were included in the analysis. Pooled estimates showed that among untreated pregnant women with syphilis, fetal loss and stillbirth were 21% more frequent, neonatal deaths were 9.3% more frequent and prematurity or low birth weight were 5.8% more frequent than among women without syphilis. Of the infants of mothers with untreated syphilis, 15% had clinical evidence of congenital syphilis. The single study that estimated infant death showed a 10% higher frequency among infants of mothers with syphilis. Substantial heterogeneity was found across studies in the estimates of all adverse outcomes for both women with syphilis (66.5% [95% confidence interval, CI: 58.0-74.1]; I(2) = 91.8%; P < 0.001) and women without syphilis (14.3% [95% CI: 11.8-17.2]; I(2) = 95.9%; P < 0.001). CONCLUSION Untreated maternal syphilis is associated with adverse pregnancy outcomes. These findings can inform policy decisions on resource allocation for the detection of syphilis and its timely treatment in pregnant women.

Does measured behavior reflect STD risk ? : An analysis of Data from a randomized controlled Behavioral intervention study

Background: Many studies measure sex behavior to determine the efficacy of sexually transmitted disease (STD)/HIV prevention interventions. Goal: To determine how well measured behavior reflects STD incidence. Study Design: Data from a trial (Project RESPECT) were analyzed to compare behavior and incidence of STD (gonorrhea, chlamydia, syphilis, HIV) during two 6‐month intervals. Results: A total of 2879 persons had 5062 six‐monthly STD exams and interviews; 8.9% had a new STD in 6 months. Incidence was associated with demographic factors but only slightly associated with number of partners and number of unprotected sex acts with occasional partners. Many behaviors had paradoxical associations with STD incidence. After combining behavior variables to compare persons with highest and lowest risk behaviors, the STD incidence ratio was only 1.7. Conclusion: Behavioral interventions have prevented STD. We found people tend to have safe sex with risky partners and risky sex with safe partners. Therefore, it is difficult to extrapolate the disease prevention efficacy of an intervention from a measured effect on behavior alone.

Lives Saved Tool supplement detection and treatment of syphilis in pregnancy to reduce syphilis related stillbirths and neonatal mortality

BackgroundGlobally syphilis is an important yet preventable cause of stillbirth, neonatal mortality and morbidity.ObjectivesThis review sought to estimate the effect of detection and treatment of active syphilis in pregnancy with at least 2.4MU benzathine penicillin (or equivalent) on syphilis-related stillbirths and neonatal mortality.MethodsWe conducted a systematic literature review of multiple databases to identify relevant studies. Data were abstracted into standardised tables and the quality of evidence was assessed using adapted GRADE criteria. Where appropriate, meta-analyses were undertaken.ResultsModerate quality evidence (3 studies) supports a reduction in the incidence of clinical congenital syphilis of 97% (95% c.i 93 – 98%) with detection and treatment of women with active syphilis in pregnancy with at least 2.4MU penicillin. The results of meta-analyses suggest that treatment with penicillin is associated with an 82% reduction in stillbirth (95% c.i. 67 – 90%) (8 studies), a 64% reduction in preterm delivery (95% c.i. 53 – 73%) (7 studies) and an 80% reduction in neonatal deaths (95% c.i. 68 – 87%) (5 studies). Although these effect estimates were large and remarkably consistent across studies, few of the studies adjusted for potential confounding factors and thus the overall quality of the evidence was considered low. However, given these large observed effects and a clear biological mechanism for effectiveness the GRADE recommendation is strong.ConclusionDetection and appropriate, timely penicillin treatment is a highly effective intervention to reduce adverse syphilis-related pregnancy outcomes. More research is required to identify the most cost-effective strategies for achieving maximum coverage of screening for all pregnant women, and access to treatment if required.

A pooled analysis of the effect of condoms in preventing HSV-2 acquisition.

BACKGROUND The degree of effectiveness of condom use in preventing the transmission of herpes simplex virus 2 (HSV-2) is uncertain. To address this issue, we performed a large pooled analysis. METHODS We identified prospective studies with individual-level condom use data and laboratory-defined HSV-2 acquisition. Six studies were identified through a review of publications through 2007: 3 candidate HSV-2 vaccine studies, an HSV-2 drug study, an observational sexually transmitted infection (STI) incidence study, and a behavioral STI intervention study. Study investigators provided us individual-level data to perform a pooled analysis. Effect of condom use was modeled using a continuous percentage of sex acts during which a condom was used and, alternatively, using absolute numbers of unprotected sex acts. RESULTS A total of 5384 HSV-2-negative people at baseline contributed 2 040 894 follow-up days; 415 persons acquired laboratory-documented HSV-2 during follow-up. Consistent condom users (used 100% of the time) had a 30% lower risk of HSV-2 acquisition compared with those who never used condoms (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.40-0.94) (P = .01). Risk for HSV-2 acquisition increased steadily and significantly with each unprotected sex act (HR, 1.16; 95% CI, 1.08-1.25) (P < .001). Condom effectiveness did not vary by gender. CONCLUSIONS To our knowledge, this is the largest analysis using prospective data to assess the effect of condom use in preventing HSV-2 acquisition. Although the magnitude of protection was not as large as has been observed with other STIs, we found that condoms offer moderate protection against HSV-2 acquisition in men and women.

Incidence of herpes simplex virus type 2 infection in 5 sexually transmitted disease (STD) clinics and the effect of HIV/STD risk-reduction counseling

The seroincidence of herpes simplex virus type 2 (HSV-2) infection was determined among 1766 patients attending sexually transmitted disease (STD) clinics and enrolled in a randomized, controlled trial of human immunodeficiency virus (HIV)/STD risk-reduction counseling (RRC). Arm 1 received enhanced RRC (4 sessions); arm 2, brief RRC (2 sessions); and arm 3, the control arm, brief informational messages. The overall incidence rate was 11.7 cases/100 person-years (py). Independent predictors of incidence of HSV-2 infection included female sex; black race; residence in Newark, New Jersey; <50% condom use with an occasional partner; and, in females, incident trichomoniasis and bacterial vaginosis. Only 10.8% of new HSV-2 infections were diagnosed clinically. Incidence rates were 12.9 cases/100 py in the control arm, 11.8 cases/100 py in arm 2, and 10.3 cases/100 py in arm 1 (hazard ratio, 0.8 [95% confidence interval, 0.6-1.1], vs. controls). The possible benefit of RRC in preventing acquisition of HSV-2 infection offers encouragement that interventions more specifically tailored to genital herpes may be useful and should be an important focus of future studies.

Seroprevalence and Correlates of Herpes Simplex Virus Type 2 Infection in Five Sexually Transmitted–Disease Clinics

The seroprevalence of herpes simplex virus type 2 (HSV-2) infection was studied among 4128 patients from sexually transmitted disease (STD) clinics who were enrolled in a randomized controlled trial of human immunodeficiency virus and STD counseling efficacy. HSV-2 seroprevalence was 40.8% and was higher in women than in men (52.0% vs. 32.4%; P<.0001) and higher in blacks than in nonblacks (48.1% vs. 29.6%; P<.0001). Among 14-19-year-old patients, 36.8% of black women and 25.8% of nonblack women were infected with HSV-2. Independent predictors of HSV-2 seropositivity included female sex, black race, older age, less education, more lifetime sex partners, prior diagnosis of syphilis or gonorrhea, and lack of HSV-1 antibody. The majority of HSV-2-seropositive persons (84.7%) had never received a diagnosis of genital herpes. HSV-2 infection is common in STD clinic attendees in the United States, even among young age groups, especially among women. Efforts to prevent genital herpes should begin at an early age. The high rate of undiagnosed HSV-2 infection likely contributes to ongoing transmission.

Using Intervention Theory to Model Factors Influencing Behavior Change Project Respect

Project RESPECT was a multisite randomized trial comparing three clinic-based interventions’ ability to increase condom use and prevent infection with HIV and sexually transmitted diseases. Because Project RESPECT had guiding concepts that determined the content of the sessions, the authors investigated how the intervention operated using these theoretical variables. Growth curve analysis and structural equation modeling estimated the correlation between intentions toward condom use and self-reports of condom use and isolated the treatment effects on mediating variables—attitudes, self-efficacy, and social norms—that predict intentions. The correlations between intentions and behavior exceeded .70 for both genders, justifying the emphasis on intentions. Project RESPECT was effective through changing attitudes and self-efficacy for females in both counseling interventions. For males, only enhanced counseling had significant effects on these two mediator variables.

Chlamydia trachomatis among Patients Infected with and Treated for Neisseria gonorrhoeae in Sexually Transmitted Disease Clinics in the United States

Context On the basis of studies of chlamydia and gonorrhea co-infection in the 1980s, guidelines recommend empirical treatment for chlamydia for patients receiving treatment for gonorrhea. The relevance of these recommendations to current practice is unknown. Contribution These 1995 data suggest that, in U.S. sexually transmitted disease clinics, the prevalence of Chlamydia trachomatis among patients infected with gonorrhea (20% in men, 42% in women) or treated for gonorrhea (19% in men, 35% in women) remains sufficiently high to warrant continued empirical therapy for chlamydia. Cautions These data are nearly a decade old. They may not apply in settings that are not sexually transmitted disease clinics. The Editors In the early 1980s, shortly after techniques for culturing Chlamydia trachomatis became available, program data and expert opinion suggested that C. trachomatis coexisted in up to 45% of patients infected with Neisseria gonorrhoeae (1). On the basis of these estimates, the U.S. Centers for Disease Control and Prevention (CDC) first suggested (1) and then formally recommended (2) that all patients treated for gonorrhea should also be treated for chlamydia. Presumptive chlamydia treatment in patients treated for gonorrhea (that is, co-treatment) has remained the standard of care, a recommendation recently renewed in the CDC Sexually Transmitted Diseases Treatment Guidelines, 2002 (3). Co-treatment was proposed as a strategy for chlamydia control at a time when chlamydia culture was performed only in research settings. Over the past two decades, diagnostic testing for C. trachomatis has dramatically improved (4). Nonetheless, many public clinics do not routinely test for C. trachomatis. Furthermore, even clinics that do test for chlamydia tend to use less sensitive, earlier-generation tests (enzyme immunoassay, DNA hybridization tests) (5) because the newer, more sensitive nucleic acid amplification tests (such as polymerase chain reaction [PCR]) are more expensive. To date, there are no accurate, rapid, point-of-care tests for chlamydia. Consequently, rapid testing (Gram stain, predominantly in men) is used for gonorrhea but not for chlamydia, and sensitive testing for gonorrhea remains more accessible in everyday practice than does chlamydia testing, particularly in public health settings where reimbursement for amplification tests is typically not available. The prevalence of sexually transmitted diseases (STDs) in the United States has changed notably since 1982, when co-treatment was introduced. Reported rates of gonorrhea in the United States have declined steadily from 418 per 100 000 persons in 1982 to 149 per 100 000 persons in 1995 to 129 per 100 000 persons in 2001 (6). National chlamydia trends have been difficult to determine because of increases in screening, test sensitivity, and case reporting. In regions where screening in women has been implemented for several years, rates of chlamydial infection seem to have decreased (6). If the prevalence of chlamydia among patients treated for gonorrhea has substantially decreased, co-treatment may no longer be indicated as a clinical or public health strategy. Despite the changes in testing technology and infection prevalences, few current data are available on the prevalence of chlamydia among patients treated for gonorrhea. However, over the past decade, estimates of chlamydial infection among persons infected with gonorrhea (that is, co-infection) have varied widely, ranging from 9% to 50% among men and 24% to 67% among women (7-21). Most of these studies, however, included small numbers of patients (7-12) or used less sensitive chlamydia tests (13-17). Furthermore, they addressed only the epidemiologic question of co-infection. Since treatment decisions must often be made before test results are available, the prevalence of chlamydia among patients treated for gonorrhea is more relevant than the prevalence among patients ultimately found to be infected with N. gonorrhoeae. Our analysis had two objectives. First, to investigate co-infection, we sought to determine the prevalence of chlamydia among patients at STD clinics who were infected with N. gonorrhoeae. Second, to assess the appropriateness of co-treatment, we sought to determine the prevalence of chlamydia among patients at STD clinics who were treated for gonorrhea, including those treated presumptively as sex partners of gonorrhea-infected persons. Methods Study Design We performed a cross-sectional analysis using baseline (enrollment) data collected from July 1993 through October 1995 for Project RESPECT, a randomized, controlled trial of counseling interventions (22). The trial was conducted among patients from public STD clinics in Baltimore, Maryland; Denver, Colorado; Long Beach, California; Newark, New Jersey; and San Francisco, California. All English-speaking patients at least 14 years of age who came to the clinics for an STD examination (evaluation of symptoms, screening or routine care, or contact with an infected partner) and who reported penilevaginal intercourse during the preceding 3 months were asked to participate. Participants found to be infected with HIV and men who identified themselves as homosexual or reported having a male sex partner during the preceding 12 months were excluded. All participants gave written, informed consent, and the institutional review boards at each site reviewed and approved the protocol. Overall, 43% of eligible patients agreed to participate in the 12-month intervention and follow-up. Study participants were routinely tested for gonorrhea, chlamydia, and several other STDs. Definitions For this analysis, we defined gonococcal infection as a positive culture for N. gonorrhoeae from a urethral or endocervical swab in men or women, respectively. We defined chlamydial infection as a positive PCR result from a urine specimen or endocervical swab in men or women, respectively. We included all participants with conclusive test results from both a gonorrhea culture and a chlamydia PCR. Nongonococcal urethritis was defined as the presence of at least 5 polymorphonuclear leukocytes per high-power field and absence of gram-negative intracellular diplococci on Gram stain. Mucopurulent cervicitis and pelvic inflammatory disease (PID) were defined according to the clinicians presumptive diagnosis at the initial visit. We considered patients to have been exposed to an STD if they had a referral card or reported that their partner was infected. We defined indications for treatment by categorizing men and women into mutually exclusive hierarchical groups. We used this approach to 1) distinguish treatment decisions made at the initial consultation from those based subsequently on laboratory test results and 2) exclude patients who would be treated for chlamydia anyway. This allowed us to determine the prevalence of chlamydia among patients treated for gonorrhea who would not, in the absence of co-treatment, be treated with an antimicrobial regimen effective against C. trachomatis. We considered that the following patients had other indications for chlamydia treatment: men with nongonococcal urethritis (C. trachomatis is the organism most commonly associated with this disorder [23]); women with mucopurulent cervicitis or PID (who are treated for several potential organisms, including C. trachomatis); and patients whose partners were diagnosed with chlamydia, nongonococcal urethritis, mucopurulent cervicitis, or PID. Next, we categorized men into six groups and women into five groups on the basis of treatment indication. We considered men to have treatment indications for chlamydia if they had 1) nongonococcal urethritis by Gram stain or 2) a sex partner with chlamydia, mucopurulent cervicitis, or PID. We considered the remaining men to have treatment indications for gonorrhea if they had 3) gram-negative intracellular diplococci, 4) a sex partner with gonorrhea, or 5) a positive gonorrhea culture. The final group comprised men 6) without treatment indications for either infection. We considered women to have treatment indications for chlamydia if they had 1) a sex partner with chlamydia or nongonococcal urethritis or 2) a clinical diagnosis of mucopurulent cervicitis or PID. We considered the remaining women to have treatment indications for gonorrhea if they had 3) a sex partner with gonorrhea or 4) a positive gonorrhea culture. The final group comprised women 5) without treatment indications for either infection. Statistical Analysis We compared characteristics of patients included in this analysis with those of patients enrolled in the original study. Chlamydia prevalence was determined for patients with laboratory-confirmed gonorrhea and for patients with each of the hierarchical treatment indications. For comparison between groups, we used chi-square tests and relative risks (RRs) with 95% CIs. MantelHaenszel weighted RRs were used to calculate summary RRs for stratified analyses, for which GreenlandRobins confidence limits were calculated. The large-sample population proportion method (24) was used to calculate 95% CIs for prevalences. Role of the Funding Source Project RESPECT was supported by CDC cooperative agreements. Chlamydia PCR kits were donated by Roche Pharmaceuticals, which was not involved in study design, conduct, analysis, or interpretation. Results Study Participants Of the 4328 patients enrolled in Project RESPECT, 443 were excluded from this analysis because they did not have conclusive results from both a gonorrhea culture and a chlamydia PCR. The remaining 3885 patients (90%), 2184 men and 1701 women, were included. Our sample was similar to the sample in the original study and to the clinic populations in that patients were young (median age, 25 years), were members of racial or ethnic minority groups (59% black, 16% Hispanic, 20% white, and 6% other), had low income (<

Toward global prevention of sexually transmitted infections (STIs): the need for STI vaccines.

5000/y in 43%), and were approximately equally distribute