Susan Ofner

Repeated Chlamydia trachomatis Genital Infections in Adolescent Women

BACKGROUND Repeated Chlamydia trachomatis infections are common among young sexually active women. The relative frequency of reinfection and antibiotic treatment failure is undefined. METHODS Adolescent women enrolled in a longitudinal cohort had behavioral and sexually transmitted infection assessments performed every 3 months, including amplification tests for C. trachomatis, ompA genotyping, and interviews and diary entries to document sex partner-specific coitus and event-specific condom use. Repeated infections were classified as reinfection or treatment failure by use of an algorithm. All infections for which treatment outcomes were known were used to estimate the effectiveness of antibiotic use. RESULTS We observed 478 episodes of infection among 210 study participants; 176 women remained uninfected. The incidence rate was 34 episodes/100 woman-years. Of the women who were infected, 121 experienced 1 repeated infections, forming 268 episode pairs; 183 pairs had complete data available and were classified using the algorithm. Of the repeated infections, 84.2% were definite, probable, or possible reinfections; 13.7% were probable or possible treatment failures; and 2.2% persisted without documented treatment. For 318 evaluable infections, we estimated 92.2% effectiveness of antibiotic use. CONCLUSIONS Most repeated chlamydial infections in this high-incidence cohort were reinfections, but repeated infections resulting from treatment failures occurred as well. Our results have implications for male screening and partner notification programs and suggest the need for improved antibiotic therapies.

Experimental infection of human volunteers with Haemophilus ducreyi: Fifteen years of clinical data and experience

Haemophilus ducreyi causes chancroid, which facilitates transmission of human immunodeficiency virus type 1. To better understand the biology of H. ducreyi, we developed a human inoculation model. In the present article, we describe clinical outcomes for 267 volunteers who were infected with H. ducreyi. There was a relationship between papule formation and estimated delivered dose. The outcome (either pustule formation or resolution) of infected sites for a given subject was not independent; the most important determinants of pustule formation were sex and host effects. When 41 subjects were infected a second time, their outcomes segregated toward their initial outcome, confirming the host effect. Subjects with pustules developed local symptoms that required withdrawal from the study after a mean of 8.6 days. There were 191 volunteers who had tissue biopsy performed, 173 of whom were available for follow-up analysis; 28 (16.2%) of these developed hypertrophic scars, but the model was otherwise safe. Mutant-parent trials confirmed key features in H. ducreyi pathogenesis, and the model has provided an opportunity to study differential human susceptibility to a bacterial infection.

Dental caries experience and association to risk indicators of remote rural populations

BACKGROUND Dental caries continues to be the most common infectious disease of childhood; however, it is no longer pandemic, but endemic in specific sectors of populations. Therefore, it is important to identify and target patients at risk of developing caries in order to develop specific preventive measures. AIM This study aims to test dental caries risk indicators for significant associations with caries severity. DESIGN Five separate, small, isolated rural villages in Mexico with varying degrees of caries prevalence were selected for this observational study. A total of 248 children were examined. Risk indicators were assessed via questionnaire and water and salt fluoride analysis. Caries severity was measured by the International Caries Detection and Assessment System (ICDAS-I). RESULTS Prevalence of caries ranged from 95% to 100% for the five villages. Mean total DMFS (decayed, missing, or filled surfaces-permanent teeth) and dmfs (decayed, missing, or filled surfaces-primary teeth) scores ranged from 2.5 to 5.0 and from 11.3 to 16.9, respectively. Multivariable models showed age and drinking soda between meals to be significantly associated with DMFS, and drinking juice and being female were significantly associated with dmfs. CONCLUSION DMFS and dmfs were high in each village, significantly different between villages, and associated with specific risk indicators.

Time From First Intercourse to First Sexually Transmitted Infection Diagnosis Among Adolescent Women

OBJECTIVE To determine the time between first intercourse and first sexually transmitted infection (STI) with Chlamydia trachomatis, Neisseria gonorrhoeae, or Trichomonas vaginalis and time between repeated infections. DESIGN Observational study. SETTING Three adolescent medicine clinics. PARTICIPANTS A cohort of 386 urban young women aged 14 to 17 years at enrollment. MAIN OUTCOME MEASURES Age at first intercourse; organism-specific interval between first intercourse and first STI diagnosis; interval between repeated infections; and age at first STI test prior to study participation. RESULTS Participants had first intercourse at a young age (first, second, and third quartiles were 13, 14, and 15 years of age, respectively). By age 15 years, 25% of the women acquired their first STI, most often C trachomatis. Median interval between first intercourse and first STI diagnosis was 2 years. Within 1 year of first intercourse, 25% had their first C trachomatis infection. Repeated infections were common; within 3.6, 6, and 4.8 months, 25% of the women with prior C trachomatis, N gonorrhoeae, and T vaginalis infection were reinfected with the respective organisms. Considerable delay in STI testing was found for those who began sex at a younger age. The median interval between first sex and first test were 4.9, 3.5, 2.1, 1.8, and 1.2 years for those who had first sex at ages 10, 11, 12, 13, and 14 years, respectively. CONCLUSIONS Timely screening and treatment are important for prevention of STI sequelae. For urban adolescent women, STI screening (especially for C trachomatis) should begin within a year after first intercourse and infected individuals should be retested every 3 to 4 months.

Accuracy of biometry in pediatric cataract extraction with primary intraocular lens implantation.

PURPOSE: To determine the accuracy of predicted postoperative refractive outcomes in pediatric patients having cataract surgery with intraocular lens (IOL) implantation and to compare them with other variables historically considered important in cataract surgery. SETTING: Tertiary care referral hospital. METHODS: This retrospective review comprised 203 eyes of 153 consecutive pediatric patients (≤18 years old) having cataract extraction with primary posterior chamber IOL implantation in the capsular bag. All cases were performed by 1 of 2 surgeons, and all refractions were performed manually by an experienced pediatric ophthalmologist using a retinoscope. RESULTS: In all patients, the mean absolute value (MAE) of the prediction error was 1.08 diopters (D) ± 0.93 (SD). Age at time of surgery and corneal (K) mean curvature were significantly correlated with the absolute value of the prediction error (P = .0006 and P = .0088, respectively). A multiple regression model showed that age at time of surgery and K mean curvature were the only 2 variables significantly associated with MAE; axial length, formula, surgeon, and A‐scan type were not significantly associated with prediction error. CONCLUSIONS: Data from 203 consecutive primary pediatric IOL implantations showed the heterogeneous nature of the variables involved in predictions of refractive outcomes in this population. The complexities of this issue support the need for specific methods of measurement and an IOL calculation formula for the pediatric population.

Chlamydia-specific CD4 T cell clones control Chlamydia muridarum replication in epithelial cells by nitric oxide-dependent and -independent mechanisms.

Chlamydia trachomatis serovars D–K are sexually transmitted intracellular bacterial pathogens that replicate in epithelial cells lining the human reproductive tract. It is clear from knockout mice and T cell depletion studies using Chlamydia muridarum that MHC class II and CD4 T cells are critical for clearing bacteria from the murine genital tract. It is not clear how CD4 T cells interact with infected epithelial cells to mediate bacterial clearance in vivo. Previous work using an epithelial tumor cell line showed that a Chlamydia-specific CD4 T cell clone was able to inhibit C. muridarum replication in vitro via induction of epithelial NO production. We have previously shown that Chlamydia-specific CD4 T cell clones can recognize and be activated by infected reproductive tract epithelial cells and block Chlamydia replication in them. We extend those observations by investigating the mechanism used by a panel of CD4 T cell clones to control Chlamydia replication in epithelial cells. We found that Chlamydia-specific CD4 T cell clones were cytolytic, but that cytolysis was not likely critical for controlling C. muridarum replication. For one, CD4 T cell clone-induced epithelial NO production was critical for controlling replication; however, the most potent CD4 T cell clones were dependent on T cell degranulation for replication control with only a minor additional contribution from NO production. We discuss our data as they relate to existing knockout mouse studies addressing mechanisms of T cell-mediated control of Chlamydia replication and their implications for intracellular epithelial pathogens in mouse models.

The Chlamydia muridarum-Induced IFN-β Response Is TLR3-Dependent in Murine Oviduct Epithelial Cells

Epithelial cells lining the murine genital tract act as sentinels for microbial infection, play a major role in the initiation of the early inflammatory response, and can secrete factors that modulate the adaptive immune response when infected with Chlamydia. C. muridarum-infected murine oviduct epithelial cells secrete the inflammatory cytokines IL-6 and GM-CSF in a TLR2-dependent manner. Further, C. muridarum infection induces IFN-β synthesis in the oviduct epithelial cells in a TRIF-dependent manner. Because murine oviduct epithelial cells express TLR3 but not TLRs 4, 7, 8, or 9, we hypothesized that TLR3 or an unknown TRIF-dependent pattern recognition receptor was the critical receptor for IFN-β production. To investigate the role of TLR3 in the Chlamydia-induced IFN-β response in oviduct epithelial cells, we used small interfering RNA, dominant-negative TLR3 mutants, and TLR3-deficient oviduct epithelial cells to show that the IFN-β secreted during C. muridarum infection requires a functional TLR3. Interestingly, we demonstrate that the TLR3 signaling pathway is not required for IFN-β synthesis in C. muridarum-infected macrophages, suggesting that there are alternate and redundant pathways to Chlamydia-induced IFN-β synthesis that seem to be dependent upon the cell type infected. Finally, because there is no obvious dsRNA molecule associated with Chlamydia infection, the requirement for TLR3 in Chlamydia-induced IFN-β synthesis in infected oviduct epithelial cells implicates a novel ligand that binds to and signals through TLR3.

Prevalence of Inadequate Blood Pressure Control Among Veterans After Acute Ischemic Stroke Hospitalization A Retrospective Cohort

Background—Reducing blood pressure (BP) after stroke reduces risk for recurrent events. Our aim was to describe hypertension care among veterans with ischemic stroke including BP control by discharge and over the 6 months after the stroke event. Methods and Results—The Office of Quality and Performance Stroke Special Study included a systematic sample of veterans hospitalized for ischemic stroke in 2007. We examined BP control (<140/90 mm Hg) at discharge excluding those who died, enrolled in hospice, or had unknown discharge disposition (n=3640, n=3382 adjusted analysis). The second outcome was BP control (<140/90 mm Hg) within 6-months after stroke, excluding patients who died/readmitted within 30 days, were lost to follow-up, or did not have a BP recorded (n=2054, n=1915 adjusted analysis). The population was 62.7% white and 97.7% men; 46.9% were <65 years of age; and 29% and 37% had a history of cerebrovascular or cardiovascular disease, respectively. Among the 3640 stroke patients, 1573 (43%) had their last documented BP before discharge as >140/90 mm Hg. Black race (adjusted odds ratio, 0.77; 95% confidence interval, 0.65 to 0.91), diabetes (odds ratio, 0.73; 95% confidence interval, 0.62 to 0.86), and hypertension history (odds ratio, 0.51; 95% confidence interval, 0.42 to 0.63) were associated with lower odds for controlled BP at discharge. Of the 2054 stroke patients seen within 6 months from their index event, 673 (32.8%) remained uncontrolled. By 6 months after the event, neither race nor diabetes was associated with BP control, whereas history of hypertension continued to have lower odds of BP control. For each 10-point increase in systolic BP >140 mm Hg at discharge, odds of BP control within 6 months after discharge decreased by 12% (95% confidence interval [8%, 18%]). Conclusions—BP values in excess of national guidelines are common after stroke. Forty-three percent of patients were discharged with an elevated BP, and 33% remained uncontrolled by 6 months.

Accuracy of IOL calculations in children: A comparison of immersion versus contact A-scan biometery

PURPOSE To evaluate the accuracy of pediatric IOL calculations performed under general anesthesia by using immersion A-scan biometry and to compare the results to those obtained using contact A-scan biometry. METHODS A retrospective review of 203 consecutive cases of pediatric cataract extraction with primary IOL implantation within the capsular bag; mean patient age was 5.52 +/- 4.19 years (range, 18 days to 18 years). Axial length measurements were performed with the contact A-scan biometry in 138 eyes, whereas immersion technique biometry was used in the remaining consecutive 65 eyes. Preoperative predictive target refraction was compared with the refractive result obtained at the 2-month postoperative visit. RESULTS The mean of the absolute value lens prediction error for all eyes was 1.08 +/- 0.93 D from the desired postoperative refractive result. Lens prediction error for the contact A-scan subgroup was 1.11 +/- 0.90 D, whereas the immersion A-scan subgroup was less at 1.03 +/- 0.98 D. This result was not statistically significant (p = 0.6442). Statistically significant correlations were found between increased lens prediction error and age at time of surgery or corneal curvature. CONCLUSIONS This retrospective, noncomparative pilot study showed no significant difference in IOL prediction error when comparing the postoperative refractive results obtained with immersion versus contact A-scan biometry in pediatric IOL calculations.

Identifying a role for Toll-like receptor 3 in the innate immune response to Chlamydia muridarum infection in murine oviduct epithelial cells.

ABSTRACT Because epithelial cells are the major cell type productively infected with Chlamydia during genital tract infections, the overall goal of our research was to understand the contribution of infected epithelial cells to the host defense. We previously showed that Toll-like receptor 3 (TLR3) is the critical pattern recognition receptor in oviduct epithelial (OE) cells that is stimulated during Chlamydia infection, resulting in the synthesis of beta interferon (IFN-β). Here, we present data that implicates TLR3 in the expression of a multitude of other innate-inflammatory immune modulators including interleukin-6 (IL-6), CXCL10, CXCL16, and CCL5. We demonstrate that Chlamydia-induced expression of these cytokines is severely disrupted in TLR3-deficient OE cells, whereas Chlamydia replication in the TLR3-deficient cells is more efficient than in wild-type OE cells. Pretreatment of the TLR3-deficient OE cells with 50 U of IFN-β/ml prior to infection diminished Chlamydia replication and restored the ability of Chlamydia infection to induce IL-6, CXCL10, and CCL5 expression in TLR3-deficient OE cells; however, CXCL16 induction was not restored by IFN-β preincubation. Our findings were corroborated in pathway-focused PCR arrays, which demonstrated a multitude of different inflammatory genes that were defectively regulated during Chlamydia infection of the TLR3-deficient OE cells, and we found that some of these genes were induced only when IFN-β was added prior to infection. Our OE cell data implicate TLR3 as an essential inducer of IFN-β and other inflammatory mediators by epithelial cells during Chlamydia infection and highlight the contribution of TLR3 to the inflammatory cytokine response.