Response to therapy following retreatment of serofast early syphilis patients with benzathine penicillin.

Persistent nontreponemal titers after treatment are common among patients with early syphilis. We retreated 82 human immunodeficiency virus-negative early syphilis participants who were serofast at 6 months using benzathine penicillin. Only 27% exhibited serological response after retreatment and after an additional 6 months of follow-up.

Aztreonam-avibactam synergy, a validation and comparison of diagnostic tools.

Introduction: Antimicrobial resistance is a growing problem that necessitates the development of new therapeutic options. Cefiderocol and aztreonam (AT) are often the last active ß-lactams for treating metallo-ß-lactamases (MBL)-producing Gram-negative bacilli. In these difficult-to-treat bacterial strains, AT resistance is frequently attributed to the co-occurrence of other resistance mechanisms. In the case of ß-lactamases they can often be inhibited by avibactam. In the present study, we evaluated the use of the double-disc synergy test (DDST) as a screening tool for the detection of synergy between AT-avibactam (ATA). We validated both the Gradient Diffusion Strips (GDSs) superposition method and the commercially available Liofilchem's ATA GDS. Materials and methods: We tested AT susceptibility in combination with ceftazidime-avibactam for 65 strains, including 18 Serine-ß-Lactamase (SBL)- and 24 MBL-producing Enterobacterales, 12 MBL-producing P. aeruginosa, and 11 S. maltophilia isolates. Interpretation was done with EUCAST breakpoints (version 13.0), AT breakpoints being used for ATA. The accuracy and validity of the GDSs superposition method and ATA GDS were evaluated using an AT GDS applied on Mueller Hinton Agar plates supplemented with avibactam (MH-AV). A DDST was performed to screen for synergy between antibiotic combinations. Results: Using MH-AV, all SBL- and MBL-positive Enterobacterales were susceptible or susceptible at increased exposure to the combination AT-avibactam. In contrast, only 2 out of the 12 (17%) P. aeruginosa strains and 9/11 (82%) of the S. maltophilia strains were susceptible- or susceptible at increased exposure for the combination of AT-avibactam. The DDST detected all synergies, demonstrating a 100% sensitivity and 100% negative predictive value for all bacterial strains. Conclusion: The DDST is a sensitive tool for screening for antibiotic synergy. Unlike S. maltophilia and SBL- and MBL-positive Enterobacterales, most MBL-positive P. aeruginosa strains remain resistant to AT-avibactam. ATA GDS should be preferred for MIC determination of the AT-avibactam combination, while the GDSs superposition method can be used as an alternative to the commercial test.

Rapid plasma reagin titer variation in the 2 weeks after syphilis therapy.

BACKGROUND: Serologic tests for syphilis results at the time of diagnosis are the basis for evaluating response to syphilis therapy. After treatment, however, serologic tests for syphilis titers may continue to increase for several weeks. We evaluated rapid plasma reagin (RPR) titer variation during the 14 days after therapy using data from a recent large, prospective randomized controlled trial. METHODS: Prospectively enrolled participants in North America and Madagascar with primary, secondary, or early latent syphilis were randomly assigned to penicillin, doxycycline (in the case of penicillin allergy), or azithromycin treatment. Blood for RPR analysis was drawn at days 0, 7, and 14 posttreatment. All RPR titers were determined simultaneously at a central laboratory. RESULTS: Four hundred and seventy patients had data available for at least 2 of 3 RPR measurements. Overall, 20% of patients showed a titer increase of at least 1 dilution in the 14 days after therapy. The greatest proportion of titer increases following therapy was observed in patients with primary syphilis. Comparing outcome of therapy using the initial (day 0) RPR titer versus the maximal RPR titer (during 14 days) resulted in outcome reclassification in 2.98% of participants. CONCLUSIONS: Despite the fact that about 20% of early syphilis patients had increases in RPR titers immediately after treatment, these changes rarely influenced assessment of therapeutic outcome. Only 3% of patients treated would have been reclassified.

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.

Notifying partners of patients with early syphilis in Madagascar: case-finding effectiveness and public health implications.

OBJECTIVE: To evaluate the case-finding effectiveness of a clinic-based partner notification effort for early syphilis in Madagascar. METHODS: We asked index cases who had proven early syphilis to identify and provide contact information of recent sex partners (in the past 3, 6, and 12 months for primary, secondary, and early latent syphilis, respectively). Named sex partners were contacted by index cases (patient notification) or, if approved by the index case, clinic staff members (provider notification); notified of their potential exposure to syphilis; and asked to come to the clinic for evaluation. We assessed case-finding effectiveness and calculated the 'brought-to-treatment' index (number of newly-diagnosed syphilis cases per number of index cases interviewed). RESULTS: Of 565 index cases, 534 reported recent sex with at least one sex partner. A total of 3167 sex partners were reported, of whom 276 were contactable (9% of 3167). Providers notified 76% and cases notified 24% of these partners. 270 partners were contacted (98% of 276), and of these, 199 presented to the clinic for evaluation (74% of 270). A total of 99 partners tested positive for syphilis and received treatment (50% of 199). The 'brought-to-treatment' index was 0.18 (99 diagnoses per 565 index cases). CONCLUSION: Partner notification was possible in this setting, resulting in treatment of syphilis-infected individuals who otherwise would likely have remained untreated. However, given <10% of the partners reported by index cases were contactable; the results highlight the limitations of partner notification and the need for additional sexually transmitted infection control strategies.

Predictors of unprotected sex among female sex workers in Madagascar: comparing semen biomarkers and self-reported data.

Research on the determinants of condom use and condom non-use generally has relied on self-reported data with questionable validity. We identified predictors of recent, unprotected sex among 331 female sex workers in Madagascar using two outcome measures: self-reports of unprotected sex within the past 48 h and detection of prostate-specific antigen (PSA), a biological marker of recent semen exposure. Multivariable logistic regression revealed that self-reported unprotected sex was associated with three factors: younger age, having a sipa (emotional partner) in the prior seven days, and no current use of hormonal contraception. The sole factor related to having PSA detected was prevalent chlamydial infection (adjusted odds ratio, 4.5; 95% confidence interval, 2.0-10.1). Differences in predictors identified suggest that determinants of unprotected sex, based on self-reported behaviors, might not correlate well with risk of semen exposure. Caution must be taken when interpreting self-reported sexual behavior measures or when adjusting for them in analyses evaluating interventions for the prevention of HIV/STIs.

Human papillomavirus and cervical neoplasia among female sex workers in Madagascar.

INTRODUCTION: Human papillomavirus (HPV) prevalence and type distribution were estimated among 90 female sex workers (FSWs) aged 18 to 58 years in Antananarivo, Madagascar. METHODS: A total of 90 FSWs aged 18 to 58 years in Antananarivo, Madagascar, were included in this study. Information on sexual and behavioral characteristics was obtained via a questionnaire. Exfoliated cervical cell specimens were collected for conventional cytologic examination and HPV DNA testing by polymerase chain reaction. The prevalence rates of HPV DNA and their corresponding 95% confidence intervals were stratified into the following 3 age groups: younger than 25, 25 to 34, and 35 years or older. To assess the association between HPV DNA positivity and sociodemographic and sexual behavioral factors, age-adjusted odds ratios and 95% confidence intervals were calculated using unconditional logistic regression. RESULTS: The HPV prevalence in exfoliated cervical cell specimens was 36.7%. The most common HPV types found were HPV-52 (11.1%), HPV-31 and -39 (each at 5.6%), and HPV-16 and -83 (each at 3.3%). The prevalence of low-grade squamous intraepithelial lesions was 3.3%, and that of atypical squamous cells of undetermined significance was 18.9%. No high-grade lesion was found. Although associations were imprecise, the HPV prevalence was higher among women who reported younger age at the first intercourse, contraceptive use, a history of cervical lesions, and no history of condom use. DISCUSSION: The prevalence rates of HPV and cervical lesions among FSWs in Madagascar appear higher than among FSW populations from other African countries with a relatively higher population-based prevalence of human immunodeficiency virus infection.

Perceived control over condom use among sex workers in Madagascar: a cohort study.

BACKGROUND: Women's perceived control over condom use has been found to be an important determinant of actual condom use in some studies. However, many existing analyses used cross-sectional data and little quantitative information exists to characterize the relationships between perceived control and actual condom use among sex worker populations. METHODS: We assessed the association between measures of perceived condom use control and self-reported use of male condoms employing data from a longitudinal pilot study among 192 sex workers in Madagascar. RESULTS: In multivariable models, a lack of perceived control over condom use with a main partner and having a main partner ever refuse to use a condom when asked were both associated with an increased number of sex acts unprotected by condoms in the past week with a main partner (RR 1.86; 95% CI 1.21-2.85; RR 1.34; 95% CI 1.03-1.73, respectively). Conversely, no measure of condom use control was significantly associated with condom use with clients. CONCLUSION: Perceived control over condom use was an important determinant of condom use with main partners, but not clients, among sex workers in Madagascar. Programs working with sex workers should reach out to main and commercial partners of sex workers to increase male condom use.

Evaluation of azithromycin resistance in Treponema pallidum specimens from Madagascar.

Treponema pallidum resistance to azithromycin has been documented in the US, Canada, and Ireland. We found no evidence of resistance to azithromycin in specimens from 141 patients with syphilitic lesions in Madagascar suggesting resistance is geographically isolated and supporting use of azithromycin as alternative treatment for early syphilis in Madagascar.

Predictors of adherent use of diaphragms and microbicide gel in a four-arm, randomized pilot study among female sex workers in Madagascar.

BACKGROUND: Participants' protocol adherence may influence assessments of the effectiveness of new female-controlled methods for sexually transmitted infection prevention. METHODS: In 2005 we conducted a randomized pilot study among female sex workers (FSWs) in Madagascar in preparation for sexually transmitted infection prevention trial of diaphragms and a vaginal microbicide. Participants (n = 192) were randomized into 4 arms: diaphragm plus microbicide (Acidform), diaphragm plus placebo gel hydroxyethyl cellulose (HEC), Acidform alone, or HEC alone. FSWs were seen weekly for 4 weeks. Using multivariable regression with generalized estimating equations, we assessed predictors of adherent product use during all sex acts in the last week. We collapsed the gel-diaphragm arms together and the gel-only arms together for this analysis. RESULTS: Between 43% and 67% of gel-diaphragm users (varying by visit) reported using study products during all sex acts in the last week, compared with 20% to 45% of gel-only users. Adherence increased with follow-up [visit 4 vs. visit 1 risk ratio (RR) for gel-diaphragm users: 1.55, P <0.01; for gel-only users, RR: 1.58, P = 0.01]. Gel-diaphragm users whose casual partners were never aware of products (RR: 2.02, P = 0.03) and who had experienced partner violence after requesting condom use (RR: 1.45, P <0.01) were more adherent. Gel-only users reporting lower sexual frequency (1-9 weekly acts vs. >or=19 acts, RR: 1.98, P <0.01) and no sex with primary partners in the past week (RR: 1.54, P = 0.02) were more adherent. CONCLUSIONS: Gel-diaphragm users had better adherence than gel-only users, and predictors of adherence differed between groups. Addressing modifiable factors during counseling sessions may improve adherence.

Effect of consistent condom use on 6-month prevalence of bacterial vaginosis varies by baseline BV status.

OBJECTIVES: Bacterial vaginosis (BV) is a condition characterized by a disturbed vaginal ecosystem which fluctuates in response to extrinsic and intrinsic factors. BV recurrence is common. To explore whether consistent condom use was associated with BV occurrence or recurrence, we compared the effect of condom use on BV prevalence after 6 months, among women with and without BV at baseline. METHODS: We used data from a randomized controlled trial, conducted among female sex workers in Madagascar during 2000-2001, that assessed the impact of adding clinic-based counselling to peer education on sexual risk behaviour and sexually transmitted infection incidence. BV was diagnosed at two time points (baseline and 6 months) according to modified Amsel criteria. Consistent condom users were women reporting no unprotected sex acts with clients in the past month or non-paying partners in the past year. Adjusted prevalence ratios (PRs) and 95% confidence intervals (CIs) were calculated using multivariable regression models. RESULTS: At baseline, 563 (56%) women had BV. Of those, 360 (72%) had BV at 6 months, compared to 158 (39%) without BV at baseline. The adjusted 6-month PR for BV comparing consistent to inconsistent condom users was 0.99 (95% CI: 0.85-1.13) among women with BV at baseline and 0.57 (95% CI: 0.30-0.94) among women without BV at baseline. CONCLUSIONS: Consistent condom use was associated with reduced BV prevalence at 6 months for women who were BV-negative at baseline, but had no effect among women who were BV-positive at baseline. Male condoms appeared to protect against BV occurrence, but not BV recurrence.

Vaginal microbicide and diaphragm use for sexually transmitted infection prevention: a randomized acceptability and feasibility study among high-risk women in Madagascar.

BACKGROUND: In preparation for a randomized controlled trial (RCT), we conducted a pilot RCT of the acceptability and feasibility of diaphragms and candidate vaginal microbicide for sexually transmitted infection prevention among high-risk women in Madagascar. METHODS: Participants were randomized to four arms: (1) diaphragm (worn continuously) with Acidform applied in the dome; (2) diaphragm (worn continuously) with placebo gel hydroxyethylcellulose (HEC) in the dome; (3) HEC applied intravaginally before sex; (4) Acidform applied intravaginally before sex. All women were given condoms. Participants were followed weekly for 4 weeks. We fit unadjusted negative binomial regression models with robust variance estimators to generate the proportion of sex acts with casual partners where condoms and experimental study products were used. RESULTS: Retention was 98% among 192 participants. Experimental product use with casual partners was high, reported in 85%, 91%, 74%, and 81% of sex acts for women in the Acidform-diaphragm, HEC-diaphragm, HEC-alone, and Acidform-alone arms, respectively. However, the proportion reporting product use during 100% of acts with casual partners over the full follow-up period was much lower: 28% to 29% in the gel-diaphragm arms and 6% to 10% in gel-alone arms. Women used condoms in 62% to 67% of sex acts with casual partners, depending on the randomization arm. Participants found diaphragms easy to insert (97%) and remove (96%). Acidform users (with or without the diaphragm) reported more genitourinary symptoms than HEC users (14% vs. 5% of visits). CONCLUSIONS: A sexually transmitted infection prevention RCT of candidate microbicide with and without the diaphragm appears acceptable and feasible in this population.

Barriers to the use of modern contraceptives and implications for woman-controlled prevention of sexually transmitted infections in Madagascar.

Globally, unplanned pregnancies and sexually transmitted infections (STIs) persist as significant threats to women's reproductive health. Barriers to the use of modern contraceptives by women might inhibit uptake of novel woman-controlled methods for preventing STIs/HIV. Use of modern contraceptives and perceptions and attitudes towards contraceptive use were investigated among women in Antananarivo, Madagascar, using qualitative research. The hypothetical acceptability of the diaphragm--a woman-controlled barrier contraceptive device that also holds promise of protecting against STIs/HIV--was assessed. Women consecutively seeking care for vaginal discharge at a public health clinic were recruited for participation in a semi-structured interview (SSI) or focus group discussion (FGD). Audiotaped SSIs and FGDs were transcribed, translated and coded for predetermined and emerging themes. Of 46 participating women, 70% reported occasional use of male condoms, mostly for preventing pregnancy during their fertile days. Although women could name effective contraceptive methods, only 14% reported using hormonal contraception. Three barriers to use of modern contraceptives emerged: gaps in knowledge about the range of available contraceptive methods; misinformation and negative perceptions about some methods; and concern about social opposition to contraceptive use, mainly from male partners. These results demonstrate the need for programmes in both family planning and STI prevention to improve women's knowledge of modern contraceptives and methods to prevent STI and to dispel misinformation and negative perceptions of methods. In addition, involvement of men will probably be a critical component of increased uptake of woman-controlled pregnancy and STI/HIV prevention methods and improved health.

Pregnancy among sex workers participating in a condom intervention trial highlights the need for dual protection.

BACKGROUND: Little is known about pregnancy rates among sex workers (SWs) or the factors that predispose SWs to this risk. We aimed to estimate the pregnancy incidence rate among Madagascar SWs participating in an intervention trial promoting use of male and female condoms and assess the influence of various predictive factors on pregnancy risk. METHODS: SWs from two study clinics in Madagascar participated in a randomized trial to assess the effect of peer education and clinic-based counseling on use of male and female condoms and prevalence of sexually transmitted infections (STIs). Women were seen every 2 months for up to 18 months; they received structured interviews at every visit, and physical exams at baseline and every 6 months thereafter. Site staff recorded information on pregnancies during interviews; pregnancy data were then merged with trial data for this analysis. RESULTS: Of 935 SWs in the analysis population, 250 became pregnant during follow-up. The cumulative probability of pregnancy was 0.149 at 6 months and 0.227 at 12 months. Comparable proportions of nonpregnant and pregnant SWs reported using highly effective contraception at baseline (approximately 16%); these users were younger and were more consistent condom users. Method switching and discontinuation were frequent. In multivariate analysis, nonuse of effective contraceptives and any self-reported unprotected sex were associated with higher incidence of pregnancy. Approximately 51% of women delivered, 13% reported a spontaneous abortion, 13% reported an induced abortion and 23% had missing pregnancy outcomes. CONCLUSIONS: Women traditionally targeted for STI/HIV preventive interventions need more comprehensive reproductive health services. In particular, SWs could benefit from targeted family planning counseling and services.

Effect of treatment assignment on intravaginal cleansing in a randomized study of the diaphragm with candidate microbicide.

BACKGROUND: Intravaginal cleansing may predispose women to adverse health outcomes and may interfere with the effectiveness and safety of female-initiated methods for preventing sexually transmitted infections (STIs). In a 4-week randomized study of 192 Malagasy sex workers, we evaluated associations between self-reported intravaginal cleansing and randomization assignment: diaphragm with viscous candidate microbicide gel (Acidform™, TOPCAD, Chicago, IL, licensed to Instead, Coppell, TX), diaphragm with placebo hydroxyethylcellulose gel (HEC, ReProtect LLC, Baltimore, MD), Acidform alone, or HEC alone. METHODS: Women were counseled to avoid intravaginal cleansing and were blinded to gel assignment. We evaluated changes in self-reported intravaginal cleansing across the study and assessed the effects of treatment assignment and covariates on frequent (more than once daily) intravaginal cleansing. Significant predictors in domain-specific models were evaluated in an all-domain multiple regression model. RESULTS: The proportion of women reporting intravaginal cleansing decreased from baseline (97%) to week 1 (82%) (p < 0.001). Self-reported frequent intravaginal cleansing decreased from baseline (87% to 56%) during the same time period (p < 0.001). In adjusted analyses, the Acidform-diaphragm group had 60% lower odds of frequent intravaginal cleansing during the study (odds ratio [OR] 0.4, 95% confidence interval [CI] 0.2-0.8) compared to the control group (HEC only). HEC-diaphragm and Acidform only users did not differ from controls. Living on the coast of Madagascar, not cohabiting, frequent intravaginal cleansing at enrollment, and high coital frequency predicted frequent intravaginal cleansing during follow-up. CONCLUSIONS: Gel characteristics and the diaphragm's presence likely influenced women's cleansing. Viscous gel delivered by a cervical barrier (such as a diaphragm) may minimize the likelihood of frequent intravaginal cleansing.

Unmet need for contraception among sex workers in Madagascar.

BACKGROUND: The study was conducted to investigate past and future pregnancy preferences and contraceptive need among Malagasy sex workers. STUDY DESIGN: We analyzed data on pregnancy and contraceptive use collected during the baseline visit of a randomized, prospective formative trial which assessed diaphragm and microbicide acceptability among sex workers. To be eligible, women could not be pregnant or planning pregnancy for the next 2 months. RESULTS: Women (N=192) from four cities (Antananarivo, Antsiranana, Mahajanga and Toamasina) reported a median of 10 sex acts per week. Fifty-two percent reported a prior unwanted pregnancy, 45% at least one induced abortion and 86% that preventing future pregnancy was moderately to very important. During the last sex act, 24% used a hormonal method, 36% used a male condom, 2% used a traditional method and 38% used no method. Nearly 30% of participants reported that pregnancy prevention was moderately or very important but used no contraception at last sex; these women were categorized as having "unmet need" for contraception. In multivariable binomial regression analyses, factors associated with unmet need included low knowledge of contraceptive effectiveness [age- and site-adjusted prevalence ratio (PR): 2.1; 95% confidence interval (CI): 1.4-3.0] and low self-efficacy to negotiate condom use (age- and site-adjusted PR: 2.0; 95% CI: 1.4-3.0). CONCLUSIONS: Among these women, prior unwanted pregnancy and induced abortion were common and preventing future pregnancy was important, yet gaps in contraceptive use were substantial. Contraceptive knowledge and self-efficacy should be improved to promote contraceptive use by sex workers.

Promoting continuous use as a strategy for achieving adherence in a trial of the diaphragm with candidate microbicide.

Women need more choices for protection from HIV and other sexually transmitted infections (STIs). We conducted a randomized 4-week study in Madagascar in preparation for a Phase III randomized controlled trial (RCT) of the diaphragm with a candidate microbicide for STI prevention. All participants completed quantitative surveys; half participated in a qualitative interview. We advised women to wear the diaphragm at all times except for daily cleaning (rather than inserting it before intercourse). The objective of this analysis was to determine whether women who followed this "continuous use" approach more often used the diaphragm for 100% of sex acts as compared with other women. If so, this would support advising continuous diaphragm use in the upcoming RCT. To meet our objective, we analyzed qualitative data thematically, developed a measure of continuous diaphragm use based on qualitative data, and used multiple regression to evaluate the measure's association with adherence to diaphragm use during 100% of sex acts. Women who wore the diaphragm continuously had 4 times higher odds of reporting diaphragm use during 100% of sex acts (OR: 4.6, 95% CI: 1.2, 24.0). If the diaphragm proves effective against STI, continuous use may help women achieve high levels of protection.

Evidence-based planning of a randomized controlled trial on diaphragm use for prevention of sexually transmitted infections.

OBJECTIVES: We conducted formative research to evaluate the acceptability and feasibility of continuous diaphragm use among low-income women highly exposed to sexually transmitted infections (STIs) in Madagascar. GOAL: To identify potential obstacles to researching the effectiveness of diaphragm use for STI prevention in a randomized controlled trial. STUDY DESIGN: Mixed methods to collect complex information. In a quantitative pilot study, women were asked to use diaphragms continuously (removing once daily for cleaning) for 8 weeks and promote consistent male condom use; they were interviewed and examined clinically during follow-up. Focus group discussions (FGDs) were conducted pre-/postpilot study. Audiotaped FGDs were transcribed, translated, coded, and analyzed. RESULTS: Ninety-three women participated in prepilot FGDs, 91 in the pilot study, and 82 in postpilot FGDs. Diaphragm use was acceptable and feasible, but participants reported lower condom use in FGDs than during interviews. Most participants reported in interviews that they used their diaphragms continuously, but FGDs revealed that extensive intravaginal hygiene practices may impede effective continuous diaphragm use. Despite counseling by study staff, FGDs revealed that participants believed the diaphragm provided effective protection against STIs and pregnancy. CONCLUSIONS: Mixed methods formative research generated information that the prospective pilot study alone could not provide and revealed contradictory findings. Results have methodological and ethical implications that affect trial design including provision of free hormonal contraceptives, and additional instructions for vaginal hygiene to avoid displacing the diaphragm. Mixed methods formative research should be encouraged to promote evidence-based study design and implementation.

Cost-effectiveness of treatment strategies for cervical infection among women at high risk in Madagascar.

BACKGROUND: According to the national guidelines developed in 2001, a woman at high risk of gonorrhea and chlamydia in Madagascar is treated presumptively at her first sexually transmitted infection clinic visit; risk-based treatment (RB) is subsequently used at 3-month visits. OBJECTIVES: To compare health and economic outcomes for a 2-stage Markov process with the following 3 cervical infection treatment policies at baseline and at 3-month follow-up visit: presumptive treatment (PT), RB, and an interim laboratory/risk-based policy. STUDY DESIGN: Cost-effectiveness analysis was used to compare the 9 treatment strategies. RESULTS: When 3-month incidence of cervical infection is <20%, the national guidelines are less costly and less effective than both RB followed by PT, and PT at both visits. CONCLUSIONS: The national guidelines are a reasonable strategy, especially in the context of resource constraints, relatively low reinfection rates, and local preferences.