Christina A. Muzny

Role of Gardnerella vaginalis in the Pathogenesis of Bacterial Vaginosis: A Conceptual Model

BACKGROUND Bacterial vaginosis (BV) is the most common cause of vaginal discharge and is associated with important public health complications such as preterm birth and acquisition or transmission of human immunodeficiency virus and sexually transmitted infections. Continued controversy concerning the pathogenesis of BV has led to a lack of progress in prevention and management of this infection. METHODS Development of a conceptual model for the pathogenesis of BV based on review of past and current research. RESULTS Our model suggests that BV is initiated by the sexual transmission of Gardnerella vaginalis, which has the appropriate virulence factors to adhere to host epithelium, create a biofilm community, and successfully compete with lactobacilli for dominance in the vaginal environment. The genetic diversity of G. vaginalis may result in virulent and avirulent strains. Symbiotic relationships with normally dormant vaginal anaerobes lead to increases in the latter which contribute to the symptoms of BV. CONCLUSIONS G. vaginalis is the pathogen responsible for the initiation of BV. Future research should focus on preventing its transmission and improved therapeutics for the biofilm infection that is caused by this pathogen and host anaerobes.

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.

Biofilms: An Underappreciated Mechanism of Treatment Failure and Recurrence in Vaginal Infections

Biofilms are microbial communities of surface-attached cells embedded in a self-produced extracellular matrix. They are of major medical significance because they decrease susceptibility to antimicrobial agents and enhance the spread of antimicrobial resistance. Biofilm-associated bacterial and fungal microorganisms have increasingly been recognized to play a role in multiple infectious diseases, particularly in their persistence and recurrence. More recently, biofilms have also been implicated in vaginal infections, notably bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC), particularly in the setting of treatment failure and recurrence. The purpose of this review is to discuss the impact of biofilms on the management and treatment of BV and recurrent VVC and highlight the need for additional research and development of novel therapeutics targeting pathogenic vaginal biofilms.

The clinical spectrum of Trichomonas vaginalis infection and challenges to management

Trichomonas vaginalis is the most common curable sexually transmitted infection worldwide. T vaginalis infections in women can range from asymptomatic to acute inflammatory vaginitis. In men, this infection is typically asymptomatic but is increasingly being recognised as a cause of non-gonococcal urethritis. Diagnosis of T vaginalis has traditionally been made by direct microscopic examination of a wet mount of vaginal fluid or through the use of culture. The recent commercial availability of nucleic acid amplification tests for the detection of T vaginalis has seen these replace culture as the gold standard for diagnosis. Nitroimidazoles (ie, metronidazole and tinidazole) are the mainstay of therapy. In the case of treatment failure due to drug resistance or in the case of a severe nitroimidazole allergy, alternative intravaginal therapies exist, although their effectiveness has not been evaluated systematically. Novel systemic agents other than nitroimidazoles for the treatment of T vaginalis are needed, and efforts to promote and support antimicrobial drug development in this setting are necessary.

Hansen's disease (Leprosy): current and future pharmacotherapy and treatment of disease-related immunologic reactions.

Hansens disease, also known as leprosy, remains an important public health problem throughout the world, including North America. The causative microbe in Hansens disease is Mycobacterium leprae, an acid‐fast organism that is difficult to grow in vitro. The nine‐banded armadillo is the major animal reservoir in the United States. Manifestations of disease vary based on host immune response and can range from tuberculoid to lepromatous leprosy (paucibacillary to multibacillary disease). Hansens disease typically affects the skin, nerves, and eyes, and patients may present with skin lesions, weakness, numbness, eye pain, or loss of vision. Definitive diagnosis is based on a combination of physical examination findings and skin biopsy and/or smear. Modern antibacterial therapy typically consists of combinations of dapsone and rifampin with or without clofazimine. Clofazimine is available only as an investigational drug through the National Hansens Disease Program. Other options include moxifloxacin, ofloxacin, minocycline, and clarithromycin. Hansens disease is associated with type 1 (reversal) and type 2 (erythema nodosum leprosum) immunologic reactions, during which the disease process appears to worsen dramatically. These reactions may occur at any time before, during, or after treatment. Antibacterial therapy should usually be continued during these reactions. Treatment options for these reactions differ based on clinical manifestations and include corticosteroids, thalidomide, pentoxiphylline, tumor necrosis factor inhibitors, and T cell inhibitors. Prompt diagnosis, antimicrobial therapy, and treatment of reactions dramatically reduce complications of the disease.

Breaking the Mold A Review of Mucormycosis and Current Pharmacological Treatment Options

Objective: To review the current literature for the pathogenesis of mucormycosis, discuss diagnostic strategies, and evaluate the efficacy of polyenes, triazoles, and echinocandins as pharmacological treatment options. Data Sources: An electronic literature search was conducted in PubMed using the MESH terms Rhizopus, zygomycetes, zygomycosis, Mucorales and mucormycosis, with search terms amphotericin B, micafungin, anidulafungin, caspofungin, extended infusion amphotericin B, liposomal amphotericin B, combination therapy, triazole, posaconazole, isavuconazole, diagnosis, and clinical manifestations. Study Selection and Data Extraction: Studies written in the English language from January 1960 to March 2016 were considered for this review article. All search results were reviewed, and the relevance of each article was determined by the authors independently. Data Synthesis: Mucormycosis is a rare invasive fungal infection with an exceedingly high mortality and few therapeutic options. It has a distinct predilection for invasion of endothelial cells in the vascular system, which is likely important in dissemination of disease from a primary focus of infection. Six distinct clinical syndromes can occur in susceptible hosts, including rhino-orbital-cerebral, pulmonary, gastrointestinal, cutaneous, widely disseminated, and miscellaneous infection. Conclusion: Diagnosis of mucormycosis is typically difficult to make based on imaging studies, sputum culture, bronchoalveolar lavage culture, or needle aspirate. Surgical debridement prior to dissemination of infection improves clinical outcomes. Surgery combined with early, high-dose systemic antifungal therapy yields greater than a 1.5-fold increase in survival rates. The Mucorales are inherently resistant to most widely used antifungal agents. Amphotericin B is appropriate for empirical therapy, whereas posaconazole and isavuconazole are best reserved for de-escalation, refractory cases, or patients intolerant to amphotericin B.

Added Benefit of Nucleic Acid Amplification Testing for the Diagnosis of Trichomonas vaginalis Among Men and Women Attending a Sexually Transmitted Diseases Clinic

BACKGROUND Trichomonas vaginalis (TV) is the most common nonviral sexually transmitted infection (STI) in the world. However, TV is not a reportable STI and, with the exception of HIV-positive women, there are no guidelines for screening in women or men. The objective of this study was to determine the added value of nucleic acid amplification tests (NAATs) for detection of TV in men and women at high risk for infection as well as correlates of infection. METHODS This was a review of clinical and laboratory data of men and women presenting to the Jefferson County Department of Health Sexually Transmitted Diseases (STD) Clinic and receiving a TV NAAT. RESULTS During 2012-2013, 6335 patients (3821 women and 2514 men) received a TV NAAT on endocervical, urethral, or urine specimens. Overall TV prevalence was 20.2%; 27.0% in women and 9.8% in men. Correlates of TV among men included age >40 years, African American race, and ≥5 polymorphonuclear cells per high-power field on urethral Gram stain. Age >40 years, African American race, leukorrhea on wet mount, elevated vaginal pH, positive whiff test, and concurrent gonococcal infection were positively associated with TV among women. TV NAAT detected approximately one-third more infections among women than wet mount alone. CONCLUSIONS TV prevalence among men and women was high in this study, suggesting that both groups should be routinely screened, including those aged >40 years. Improved detection of TV by routine implementation of NAATs should result in better control of this common, treatable STI.

Symptomatic Trichomonas vaginalis infection in the setting of severe nitroimidazole allergy: successful treatment with boric acid

This report describes a patient with symptomatic Trichomonas vaginalis infection who was unable to tolerate nitroimidazole drugs because of severe hypersensitivity, for which desensitisation was not possible. Use of intravaginal clotrimazole, intravaginal paromomycin, intravaginal furazolidone, povidone-iodine douches, and oral nitazoxanide were unsuccessful in eradicating the patients T. vaginalis infection. A 2-month course of intravaginal topical boric acid subsequently achieved a complete symptomatic cure and the patient remained T. vaginalis wet prep- and culture-negative 60 days after treatment.

Genetic Characterization of Trichomonas vaginalis Isolates by Use of Multilocus Sequence Typing

ABSTRACT In this study, we introduce a multilocus sequence typing (MLST) scheme, comprised of seven single-copy housekeeping genes, to genetically characterize Trichomonas vaginalis. Sixty-eight historical and recent isolates of T. vaginalis were sampled from the American Type Culture Collection and female patients at area health care facilities, respectively, to assess the usefulness of this typing method. Forty-three polymorphic nucleotide sites, 51 different alleles, and 60 sequence types were distinguished among the 68 isolates, revealing a diverse T. vaginalis population. Moreover, this discriminatory MLST scheme retains the ability to identify epidemiologically linked isolates such as those collected from sexual partners. Population genetic and phylogenetic analyses determined that T. vaginalis population structure is strongly influenced by recombination and is composed of two separate populations that may be nonclonal. MLST is useful for investigating the epidemiology, genetic diversity, and population structure of T. vaginalis.

Sexual partnership characteristics of African American women who have sex with women; impact on sexually transmitted infection risk.

Background African American women who have sex with women (WSW) are emerging as a population at risk for sexually transmitted infections (STIs). The objectives of this study were to explore partnership characteristics for a cohort of African American WSW and evaluate those characteristics as potential risk factors for STIs. In addition, we aimed to determine STI diagnoses and identify predictors of STI infection. Methods Women who have sex with women presenting to a sexually transmitted disease clinic in Birmingham, AL, completed a questionnaire and were tested for bacterial vaginosis, trichomoniasis, chlamydia, gonorrhea, Mycoplasma genitalium, syphilis, HIV, and herpes simplex virus type 2. Results A total of 163 women were enrolled: 78 WSW and 85 women who have sex with women and men (WSWM) (based on report of past year sexual behavior). Both WSW and WSWM reported similar numbers of female partners over the lifetime, past year, and past month; however, WSWM reported significantly more lifetime male partners, thus having a higher overall number of sexual partners. Women who have sex with women and men were more likely to report new or casual partner(s), group sex, history of STIs, and sex with partner(s) known to have STIs. Overall, WSWM were more likely to have a current diagnosis of bacterial vaginosis, a current diagnosis of a curable STI, or a diagnosis of a noncurable STI (85% vs. 56%, P < 0.01). Conclusions African American WSW are not a homogeneous group, and their sexual health may be directly or indirectly influenced by male partners. A better understanding of the distinctions and differences between African American WSW and WSWM will enable health care providers to improve the quality of care provided.