Rate of Decline in Nontreponemal Antibody Titers and Seroreversion After Treatment of Early Syphilis.

BACKGROUND: Syphilis management is complex and demonstration of treatment response requires monitoring of nontreponemal antibody titers for a ≥ 4-fold decline and/or seroreversion to nonreactive titers. METHODS: We evaluated data from a multicenter clinical trial of syphilis treatment conducted from 2000 to 2009 involving human immunodeficiency virus (HIV)-negative patients 18 years or older with early syphilis. To assess the rate of titer decline and seroreversion after effective therapy, rapid plasma reagin (RPR) titers were analyzed at 1, 3, 6, 9, and 12 months among patients with an appropriate treatment response. We plotted the rate of RPR titer decline after treatment, estimated the frequency of seroreversion, and conducted multivariate analyses to assess characteristics associated with seroreversion. RESULTS: Among 369 (79.4%) of 465 HIV-negative patients with early syphilis who had an appropriate treatment response, 333 participants had complete RPR data over 12 months. Although the decline in RPR titers was ≥ 4-fold among 88.0% (293/333) of participants at 3 months and ≥ 8-fold among 77.8% at 6 months, only 9.6% achieved complete RPR seroreversion at 6 months and 17.1% at 12 months after therapy. Male sex (adjusted odds ratio, 4.3; 95% confidence interval, 1.8-10.5) and baseline RPR titers ≤ 1:32 (adjusted odds ratio, 14.5; 95% confidence interval, 6.8-31.2) were associated with higher odds of seroreversion compared with females and titers > 1:32, respectively. CONCLUSIONS: Despite a ≥ 4-fold RPR titer decline after treatment, the majority of HIV-negative patients with early syphilis failed to have seroreversion at 12 months. Nontreponemal antibody titers often persist despite an appropriate treatment response.

A systematic review of the effects of visual inspection with acetic acid, cryotherapy, and loop electrosurgical excision procedures for cervical dysplasia in HIV-infected women in low- and middle-income countries.

BACKGROUND: Cervical cancer, almost all of which is caused by human papillomavirus, accounts for 12% of female cancers worldwide and is more common among HIV-infected women. Nine of 10 deaths from cervical cancer occur in low- and middle-income countries (LMICs). Simple screening methods and outpatient treatment of precursor lesions save lives but the benefit of these interventions among HIV-infected women is uncertain. OBJECTIVE: We reviewed evidence of the effects of screening with visual inspection with acetic acid (VIA), and outpatient treatment for cervical precancer among HIV-infected women in LMIC. METHODS: A systematic review of articles published from January 1995 through July 2013 was conducted using key terms for VIA cervical screening, cervical precancer treatment with cryotherapy or loop electrosurgical excision procedure, HIV-infected women, low-resource settings, and outcomes, including morbidity and mortality. RESULTS: Of 2159 articles screened, 14 met inclusion criteria; all considered only morbidity outcomes. No articles dealt with the long-term impact of screening/treatment on cervical cancer incidence or mortality among HIV-infected women. Articles reported on performance of VIA, prevalence of cervical dysplasia, and complications and rates of recurrent dysplasia after treatment. CONCLUSIONS: Dysplasia prevalence and recurrence were higher among HIV-infected compared with HIV-uninfected women but morbidity from treatment was similar. Few data exist on long-term outcomes of VIA, cryotherapy, or loop electrosurgical excision procedure interventions among HIV-infected women in LMIC; longer-term outcomes research is needed to assess the effects of VIA or other screening modalities and outpatient treatment on prevention of cervical cancer among HIV-infected women.

Predictors of serological cure and Serofast State after treatment in HIV-negative persons with early syphilis.

BACKGROUND: Syphilis management requires serological monitoring after therapy. We compared factors associated with serological response after treatment of early (ie, primary, secondary, or early latent) syphilis. METHODS: We performed secondary analyses of data from a prospective, randomized syphilis trial conducted in the United States and Madagascar. Human immunodeficiency virus (HIV)-negative participants aged ≥ 18 years with early syphilis were enrolled from 2000-2009. Serological testing was performed at baseline and at 3 and 6 months after treatment. At 6 months, serological cure was defined as a negative rapid plasma reagin (RPR) test or a ≥4-fold decreased titer, and serofast status was defined as a ≤ 2-fold decreased titer or persistent titers that did not meet criteria for treatment failure. RESULTS: Data were available from 465 participants, of whom 369 (79%) achieved serological cure and 96 (21%) were serofast. In bivariate analysis, serological cure was associated with younger age, fewer sex partners, higher baseline RPR titers, and earlier syphilis stage (P ≤ .008). There was a less significant association with Jarisch-Herxheimer reaction after treatment (P = .08). Multivariate analysis revealed interactions between log-transformed baseline titer with syphilis stage, in which the likelihood of cure was associated with increased titers among participants with primary syphilis (adjusted odds ratio [AOR] for 1 unit change in log(2) titer, 1.83; 95% confidence interval [CI], 1.25-2.70), secondary syphilis (AOR, 3.15; 95% CI, 2.14-4.65), and early latent syphilis (AOR, 1.86; 95% CI, 1.44-2.40). CONCLUSIONS: Serological cure at 6 months after early syphilis treatment is associated with age, number of sex partners, Jarisch-Herxheimer reaction, and an interaction between syphilis stage and baseline RPR titer.

A phase III equivalence trial of azithromycin versus benzathine penicillin for treatment of early syphilis.

BACKGROUND: Syphilis remains an important source of morbidity worldwide. Long-acting penicillin is the only therapy currently recommended for syphilis in much of the world. Because of hesitation to use penicillin for fear of anaphylaxis, there is a need for an effective, well-tolerated alternative to penicillin for syphilis therapy. METHODS: This multicenter, randomized clinical trial was conducted in clinics for the treatment of persons with sexually transmitted diseases. We compared serological cure rates for human immunodeficiency virus (HIV)-negative persons with early syphilis treated with azithromycin at a dosage of 2.0 g administered orally as a single dose with cure rates for those treated with benzathine penicillin G at a dosage of 2.4 million units administered intramuscularly. RESULTS: A total of 517 participants were enrolled in the trial. In the intention-to-treat analysis, after 6 months of follow-up, serological cure was observed in 180 (77.6%) of 232 azithromycin recipients and 186 (78.5%) of 237 penicillin recipients (1-sided lower bound 95% confidence interval, 7.2%). Nonserious adverse events were more common among azithromycin recipients than they were among penicillin recipients (61.5% vs 46.3%), and such adverse events were accounted for, in large part, by self-limited gastrointestinal complaints. CONCLUSIONS: In this trial, the efficacy of azithromycin at a dosage of 2.0 g administered orally was equivalent to that of benzathine penicillin G for the treatment of early syphilis in persons without HIV infection.

Prevalence monitoring in syphilis surveillance: results from a multicenter research program.

BACKGROUND: Syphilis seroprevalence data can be used as an independent measure of syphilis trends and to augment syphilis case report data for program planning. The prevalence of reactive syphilis serology in jails, delivery rooms, and drug treatment centers was examined from 1995 to 1999. Prevalence was evaluated by age and gender at each site and compared with county primary and secondary syphilis case rates. Annual prevalence of high titer-reactive serology in jails was compared with primary and secondary syphilis case rates. GOAL: The goal was to examine trends in syphilis seroprevalence and to evaluate the relationship of trends in seroprevalence to reported cases. STUDY DESIGN: This was a cross-sectional survey. RESULTS: Prevalence of reactive serology and high titer-reactive serology was lowest among women in delivery rooms (2.9% and 0.4%, respectively) and highest among women in jails (11.1% and 4.1%, respectively), indicating substantial recently treated or active infection among women in jails. Trends in high titer-reactive serology were similar to primary and secondary syphilis case rates. CONCLUSION: The prevalence of high titer-reactive serology can provide valuable information about community syphilis morbidity for use in prevention and control programs.

General practitioners with a special clinical interest: a model for improving respiratory disease management.

Health care technology is continuously moving forward with great advances in all fields of medicine. The way in which health care is delivered has been stuck in a primary care/secondary care model, which is failing to meet patients' needs. Existing structures are inefficient because they do not maximise use of skills. A new way of delivering services is proposed using an intermediate level specialist--a general practitioner with a special clinical interest (GPSCI), to increase access at a location close to the patient while giving support to the wider primary health community. We explore how the role of GPSCI might work using the field of respiratory medicine as an exemplar. The concept is transferable to other therapeutic areas.