Imran Sunesara

Sexually transmitted infections and risk behaviors among African American women who have sex with women: does sex with men make a difference?

Objective: We sought to determine the prevalence of infection with Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, Mycoplasma genitalium, syphilis, and HIV among African American women who have sex with women (AAWSW), and compare sociodemographics, sexual risk behavior characteristics, and STI diagnoses among women reporting sex exclusively with women (exclusive AAWSW) to women reporting sex with both women and men (AAWSWM) during the past 12 months. Methods: Eligible women presenting to the Mississippi State Department of Health STD Clinic between February 2009 and October 2010 were invited to participate. A survey on sociodemographics, sexual history, and sexual risk behavior characteristics was completed. Women were tested for the presence of C. trachomatis, N. gonorrhoeae, T. vaginalis, M. genitalium, syphilis, and HIV. Results: A total of 196 African American women were enrolled; 56.6% of all women reported engaging in sexual activity exclusively with women (AAWSW) during the past 12 months and 40.8% reported engaging in sexual activity with both men and women (AAWSWM). As compared with exclusive AAWSW, AAWSWM were significantly more likely to report prior infection with C. trachomatis (35.0% vs. 13.5%, P < 0.001), prior infection with N. gonorrhoeae (28.75% vs. 2.7%, P < 0.001), and transactional sex (18.8% vs. 2.7%, P = 0.001). Additionally, 13.8% of AAWSWM reported having sex with a homosexual or bisexual man during the past 12 months. Trichomoniasis was diagnosed in 18.3% of all women, C. trachomatis in 11.0%, M. genitalium in 7.6%, and N. gonorrhoeae in 3.7%. There were no cases of syphilis or HIV. AAWSWM were significantly more likely to be diagnosed with trichomoniasis (25.0% vs. 13.5%, P = 0.04), C. trachomatis (22.5% vs. 2.7%, P < 0.001), N. gonorrhoeae (7.5% vs. 0.9%, P = 0.01), or any STI (47.5% vs. 18.3%, P < 0.001) than exclusive AAWSW. Conclusions: AAWSW in this study were at high risk for STI. AAWSWM, as a subgroup, may demonstrate heightened sexual risk-taking behaviors and higher STI rates compared with exclusive AAWSW. Sexual health services provided to AAWSW should take into account partner gender heterogeneity when counseling and screening for STI.

A high LDH to AST ratio helps to differentiate pregnancy-associated thrombotic thrombocytopenic purpura (TTP) from HELLP syndrome

Objective: Differentiating between pre-eclampsia/HELLP syndrome and pregnancy-associated thrombotic thrombocytopenic purpura (TTP) is difficult but important in order to undertake timely and potentially life-saving plasma exchange (PEX) therapy for TTP recovery. We review our institutional experience with pregnancy-associated TTP and determine if the ratio of LDH to AST reliably distinguishes patients with TTP from those with HELLP syndrome. Study design: This is a retrospective case control study of all pregnant/puerperal patients with TTP from a single tertiary care center during 1986–2006. Laboratory findings in patients with TTP were compared to patients who met all criteria for class 1 or 2 HELLP syndrome within the first 24 hours of hospital admission during 2000–2007. Results: Thirteen pregnant (n = 10) or puerperal (n = 3) patients with TTP were identified; 11 cases were primary, 2 were recurrent. TTP laboratory findings included LDH to AST ratios of 77 ± 42.17; Patients with HELLP syndrome (N = 83) had significantly lower LDH to AST ratios of 20.04 ± 2.13. Based on an ROC analysis, an LDH/AST ratio ≥22.12 discriminates well between TTP and antenatal HELLP subjects (AUC = 0.99). Conclusion: A high LDH to AST ratio >22.12 suggests that TTP is a more likely diagnosis than HELLP syndrome in the third trimester pregnant patient, presenting with findings that could be compatible with either diagnosis. In these circumstances, it is advisable to obtain hematology consultation and to consider PEX implementation.

Hellp syndrome and composite major maternal morbidity: importance of Mississippi classification system

Abstract Objective: We explored the prevalence of Composite Major Maternal Morbidity (CMMM) for patients with severe preeclampsia (SPRE) and each class or category of HELLP syndrome. Methods: In a retrospective cohort study from 2000 to 2010, we reviewed maternal charts of patients categorized with complete or partial HELLP syndrome. From 2005 to 2007, the maternal charts for every patient with a diagnosis of SPRE without HELLP syndrome were also evaluated for comparison. The CMMM for each patient group included cardiopulmonary; hematologic/coagulation, central nervous system/visual, hepatic or renal complications. During the study interval patients with class 1 and class 2 HELLP syndrome received Mississippi Protocol management. Results: Four hundred and ninety-five mothers had a form of HELLP syndrome in years 2000–2010; 688 mothers experienced a non-HELLP severe form of preeclampsia during 2005–2007. The prevalence of CMMM for each patient group was: class 1 = 44%; class 2 = 13%; class 3 = 24%; partial HELLP = 20% and SPRE = 18%. CMMM for class 1 HELLP syndrome is significantly higher than all other groups (p < 0.001). Conclusions: Patients who develop class 1 HELLP syndrome have significantly higher CMMM. Avoiding this most advanced stage of HELLP syndrome and minimizing the development of new MMM becomes a measure of medical management effectiveness and a tool to assess overall quality of care.

Maternal hemodynamics by thoracic impedance cardiography for normal pregnancy and the postpartum period.

OBJECTIVE: To establish normative impedance cardiography values for the second half of pregnancy and up to 48 hours postpartum after either vaginal or cesarean delivery. METHODS: A single-center prospective observational institutional review board-approved study of normotensive women (n=168) using thoracic impedance cardiography performed at specific times during gestation. Antepartum testing was performed at three time periods: 20–27 weeks, 28–33 weeks, and 34–40 weeks of gestation. Postpartum testing was undertaken after the immediate puerperium at 6–23 hours and 24–48 hours after vaginal or cesarean delivery. Data analysis was performed using STATA software; data are expressed as mean±standard deviation. RESULTS: All seven of the patient groups studied were comparable with regard to demographic features; 80% of the study participants were African American. Group means obtained between 20 and 40 weeks of gestation and postpartum after vaginal and cesarean delivery fell within the “normal range” of the hemodynamic graph that was developed to associate mean arterial pressure and systemic vascular resistance. The thoracic fluid content group means in both vaginal and cesarean delivery groups were higher than the antepartum patient groups. The thoracic fluid content mean after cesarean delivery at 48 hours is significantly higher than the mean value recorded between 20 and 27 weeks of gestation (P<.05). The systemic vascular resistance systemic vascular resistance means in each of the postpartum groups were significantly higher than the late second-trimester group means recorded at 20–27 weeks of gestation (P<.05). CONCLUSION: The normative values reported in this investigation can be used to interpret and assess similarly tested patients with hypertensive or otherwise complicated pregnancy. LEVEL OF EVIDENCE: III

Characterization of the Vaginal Microbiota among Sexual Risk Behavior Groups of Women with Bacterial Vaginosis

Background The pathogenesis of bacterial vaginosis (BV) remains elusive. BV may be more common among women who have sex with women (WSW). The objective of this study was to use 454 pyrosequencing to investigate the vaginal microbiome of WSW, women who have sex with women and men (WSWM), and women who have sex with men (WSM) with BV to determine if there are differences in organism composition between groups that may inform new hypotheses regarding the pathogenesis of BV. Methods Vaginal swab specimens from eligible women with BV at the Mississippi State Department of Health STD Clinic were used. After DNA extraction, 454 pyrosequencing of PCR-amplified 16S rRNA gene sequences was performed. Sequence data was classified using the Ribosomal Database Program classifer. Complete linkage clustering analysis was performed to compare bacterial community composition among samples. Differences in operational taxonomic units with an abundance of ≥2% between risk behavior groups were determined. Alpha and beta diversity were measured using Shannon’s Index implemented in QIIME and Unifrac analysis, respectively. Results 33 WSW, 35 WSWM, and 44 WSM were included. The vaginal bacterial communities of all women clustered into four taxonomic groups with the dominant taxonomic group in each being Lactobacillus, Lachnospiraceae, Prevotella, and Sneathia. Regarding differences in organism composition between risk behavior groups, the abundance of Atopobium (relative ratio (RR)=0.24; 95%CI 0.11-0.54) and Parvimonas (RR=0.33; 95%CI 0.11-0.93) were significantly lower in WSW than WSM, the abundance of Prevotella was significantly higher in WSW than WSWM (RR=1.77; 95%CI 1.10-2.86), and the abundance of Atopobium (RR=0.41; 95%CI 0.18-0.88) was significantly lower in WSWM than WSM. Overall, WSM had the highest diversity of bacterial taxa. Conclusion The microbiology of BV among women in different risk behavior groups is heterogeneous. WSM in this study had the highest diversity of bacterial taxa. Additional studies are needed to better understand these differences.

Validation of a Genomics-Based Hypothetical Adverse Outcome Pathway: 2,4-Dinitrotoluene Perturbs PPAR Signaling Thus Impairing Energy Metabolism and Exercise Endurance

2,4-dinitrotoluene (2,4-DNT) is a nitroaromatic used in industrial dyes and explosives manufacturing processes that is found as a contaminant in the environment. Previous studies have implicated antagonism of PPARα signaling as a principal process affected by 2,4-DNT. Here, we test the hypothesis that 2,4-DNT-induced perturbations in PPARα signaling and resultant downstream deficits in energy metabolism, especially from lipids, cause organism-level impacts on exercise endurance. PPAR nuclear activation bioassays demonstrated inhibition of PPARα signaling by 2,4-DNT whereas PPARγ signaling increased. PPARα (-/-) and wild-type (WT) female mice were exposed for 14 days to vehicle or 2,4-DNT (134 mg/kg/day) and performed a forced swim to exhaustion 1 day after the last dose. 2,4-DNT significantly decreased body weights and swim times in WTs, but effects were significantly mitigated in PPARα (-/-) mice. 2,4-DNT decreased transcript expression for genes downstream in the PPARα signaling pathway, principally genes involved in fatty acid transport. Results indicate that PPARγ signaling increased resulting in enhanced cycling of lipid and carbohydrate substrates into glycolytic/gluconeogenic pathways favoring energy production versus storage in 2,4-DNT-exposed WT and PPARα (-/-) mice. PPARα (-/-) mice appear to have compensated for the loss of PPARα by shifting energy metabolism to PPARα-independent pathways resulting in lower sensitivity to 2,4-DNT when compared with WT mice. Our results validate 2,4-DNT-induced perturbation of PPARα signaling as the molecular initiating event for impaired energy metabolism, weight loss, and decreased exercise performance.

Bacterial vaginosis among African American women who have sex with women.

Background Bacterial vaginosis (BV) is a frequent cause of vaginal discharge that may be more common among women reporting sex with women (WSW). The objective of this study was to determine the prevalence of BV and predictors of infection among a sample of African American WSW. Methods African American WSW aged 18 years or older presenting to the Mississippi State Department of Health STD Clinic between 2009 and 2010 and reporting a history of sexual activity with a female partner during the preceding year were invited to participate. A survey on sexual history and sexual behavior characteristics was completed. Bacterial vaginosis was defined by Amsel criteria. Associations with participant characteristics were determined using logistic regression analysis. Results Bacterial vaginosis was diagnosed in 93 (47.4%) of 196 women. Bisexual identity (odds ratio [OR], 1.94; 95% confidence interval [CI], 1.03–3.66; P = 0.04), douching within the past 30 days (OR, 1.93; 95% CI, 1.09–3.43; P = 0.02), age 18 years or less at first sexual encounter with a female partner (OR, 3.18; 95% CI, 1.16–8.71; P = 0.02), and report of more than 1 lifetime male sexual partners (OR, 1.94; 95% CI, 1.01–3.74; P = 0.04) were significant predictors of BV in bivariate analysis. Bacterial vaginosis was less common among women who reported more than 1 lifetime female sexual partner (OR, 0.26; 95% CI, 0.09–0.76; P = 0.01). In multivariable analysis, age 18 years or less at first sex with a female partner approached significance, while report of 1 lifetime female sexual partner remained strongly associated with BV. Conclusions Bacterial vaginosis was common in this sample of African American WSW and significantly associated with report of 1 lifetime female sexual partner.

Increased Circulating Anti-inflammatory Cells in Marathon-trained Runners.

Exercise training can alter immune function. Marathon training has been associated with an increased susceptibility to infectious diseases and an increased activity of inflammatory-based diseases, but the precise mechanisms are unknown. The purpose of this study was to compare levels of circulating CD4+  T cell subsets in the periphery of marathon-trained runners and matched non-marathon controls. 19 recreational marathoners that were 4 weeks from running a marathon and 19 demographically-matched healthy control subjects had the percentage of CD4+ T cell subpopulations (T helper 1, T helper 2, T helper 1/T helper 2 ratio, regulatory T cells, CD4+ IL10+, and CD4+ TGFβ+ (Transforming Growth Factor-beta) measured by flow cytometry. Marathon-trained runners had significantly less T helper 1 and regulatory T cells and significantly more T helper 2, CD4+ IL10+, and TGFβ+ cells than the control subjects. The alterations in the percentage of T helper 1 and T helper 2 cells led to a significantly lower T helper 1/T helper 2 ratio in the marathon-trained runners. These data suggest that endurance-based training can increase the number of anti-inflammatory cells. This may be a potential mechanism for the increased incidence of both infectious and inflammatory diseases observed in endurance athletes.

Association between BVAB1 and high Nugent scores among women with bacterial vaginosis

As part of a larger study using 454 pyrosequencing to investigate the vaginal microbiota of women with bacterial vaginosis (BV), we found an association between a novel BV-associated bacterium (BVAB1) and high Nugent scores and propose that BVAB1 is the curved Gram-negative rod traditionally identified as Mobiluncus spp. in vaginal Gram stains.

Polyamine transporter in Streptococcus pneumoniae is essential for evading early innate immune responses in pneumococcal pneumonia

Streptococcus pneumoniae is the most common bacterial etiology of pneumococcal pneumonia in adults worldwide. Genomic plasticity, antibiotic resistance and extreme capsular antigenic variation complicates the design of effective therapeutic strategies. Polyamines are ubiquitous small cationic molecules necessary for full expression of pneumococcal virulence. Polyamine transport system is an attractive therapeutic target as it is highly conserved across pneumococcal serotypes. In this study, we compared an isogenic deletion strain of S. pneumoniae TIGR4 in polyamine transport operon (ΔpotABCD) with the wild type in a mouse model of pneumococcal pneumonia. Our results show that the wild type persists in mouse lung 24 h post infection while the mutant strain is cleared by host defense mechanisms. We show that intact potABCD is required for survival in the host by providing resistance to neutrophil killing. Comparative proteomics analysis of murine lungs infected with wild type and ΔpotABCD pneumococci identified expression of proteins that could confer protection to wild type strain and help establish infection. We identified ERM complex, PGLYRP1, PTPRC/CD45 and POSTN as new players in the pathogenesis of pneumococcal pneumonia. Additionally, we found that deficiency of polyamine transport leads to up regulation of the polyamine synthesis genes speE and cad in vitro.