Edward W Hook

• University of Alabama at Birmingham

Importance Syphilis rates have been increasing in the US for the past decade. The incidence of the Jarisch-Herxheimer reaction (JHR) after penicillin treatment for early syphilis is reported to range from 8% to 56%. Objectives To prospectively assess the incidence of JHR signs and symptoms among adults with early syphilis treated with benzathine p...

There is an unmet need for developing drugs for the treatment of gonorrhea, due to rapidly evolving resistance of Neisseria gonorrhoeae against antimicrobial drugs used for empiric therapy, an increase in globally reported multidrug resistant cases, and the limited available therapeutic options. Furthermore, few drugs are under development. Develop...

Background Treponema pallidum (T. pallidum) prevalence and burden at oral and lesion sites in adults with early syphilis were assessed by qPCR. Factors associated with oral shedding were also examined. Methods Pre-treatment oral and lesion swabs were collected from adults with early syphilis in a US multicenter syphilis treatment trial. Oral swabs...

Background Syphilis rates in the United Stated (U.S.) have increased steadily for over a decade. Despite over 75 years as the drug of choice for syphilis treatment, controversy persists on optimal duration of therapy with benzathine penicillin G (BPG) for persons with early(primary, secondary, and early latent) syphilis, particularly for persons co...

Background Treponema pallidum (T. pallidum) is transmitted from person to person by direct contact with widespread dissemination early after acquisition. Current syphilis diagnostic testing is limited to darkfield microscopy from visible lesions and serologic antibody detection. T. pallidum molecular diagnostics are urgently needed. Methods As par...

Sequencing of most Treponema pallidum genomes excludes repeat regions in tp0470 and the tp0433 gene, encoding the acidic repeat protein ( arp ). As a first step to understanding the evolution and function of these genes and the proteins they encode, we developed a protocol to nanopore sequence tp0470 and arp genes from 212 clinical samples collecte...

Sequencing of most Treponema pallidum ( T. pallidum ) genomes excludes repeat regions in tp0470 and the tp0433 gene, encoding the acidic repeat protein ( arp ). As a first step to understanding the evolution and function of these genes and the proteins they encode, we developed a protocol to nanopore sequence tp0470 and arp genes from 212 clinical...

Among 865 adults with early syphilis considered for a multicenter treatment trial, 234 (27%) were excluded prior to enrollment due to bacterial STI coinfection. Coinfection with Neisseria gonorrhoeae (29%), Chlamydia trachomatis (22%), or both (23%) were common. Study findings highlight the need for comprehensive bacterial STI screening in syphilis...

Research using nucleic acid amplification tests (NAATs) have repeatedly found rectal and oropharyngeal infections with Chlamydia trachomatis and Neisseria gonorrhoeae to be common and potentially more difficult to treat than genital infections. Unfortunately, public health and patient care efforts have been hampered by the lack of FDA-cleared NAATs...

In spite of its immutable susceptibility to penicillin, Treponema pallidum (T. pallidum) subsp. pallidum continues to cause millions of cases of syphilis each year worldwide, resulting in significant morbidity and mortality and underscoring the urgency of developing an effective vaccine to curtail the spread of the infection. Several technical chal...

Despite decades of medical, diagnostic, and public health advances related to diagnosis and management of sexually transmitted infections (STI), rates of reportable STIs continue to grow. A 2021 National Academies of Sciences, Engineering, and Medicine report on the current state of STI management and prevention in the United States, entitled Sexua...

In spite of its immutable susceptibility to penicillin, Treponema pallidum ( T. pallidum ) subsp. pallidum continues to cause millions of cases of syphilis each year worldwide, resulting in significant morbidity and mortality and underscoring the urgency of developing an effective vaccine to curtail the spread of the infection. Several technical ch...

STIs represent a sizable, longstanding, and growing challenge and a national public health priority. A recent National Academies report outlines new directions for STI prevention and control, including the adoption of a new sexual health paradigm and broader ownership and accountability for addressing sexual health and STIs among diverse clinical a...

Background: Nearly 14% of US women report any lifetime infertility which is associated with healthcare costs and psychosocial consequences. Tubal factor infertility (TFI) often occurs as a result of sexually transmitted diseases and subsequent pelvic inflammatory disease. We sought to evaluate for and describe potential racial disparities in TFI a...

Background: Chlamydial infection is associated with tubal factor infertility (TFI); however, assessment of prior chlamydial infection and TFI is imperfect. We previously evaluated a combination of serological assays for association with TFI. We now describe the chlamydial contribution to TFI using a newer Chlamydia trachomatis Pgp3 enhanced serolo...

Background: The reverse algorithm for syphilis diagnosis consists of a treponemal antibody screening immunoassay followed by confirmatory non-treponemal antibody testing. It is increasingly used in the US despite studies suggesting limited cost-effectiveness in high-prevalence groups. Methods: In this retrospective cross-sectional study, we incl...

Background Increasing multi-drug resistance rates in Neisseria gonorrhoeae have raised concerns and an urgent call for new antibiotics for treatment of gonorrhoea. Several decades of subdued drug development in this field and the recent failures of two new antibiotics to show non-inferiority compared to the current first-line antibiotics ceftriaxon...

Data from a large prospective multicenter clinical validation study of a nucleic acid amplification in vitro diagnostic test for Mycoplasma genitalium were analyzed to describe the prevalence of M. genitalium infection, risk factors, and disease associations in female and male patients seeking care in diverse geographic regions of the United States...

Progressive antimicrobial resistance in Neisseria gonorrhoeae, Mycoplasma genitalium, and Trichomonas vaginalis has created a pressing need for treatment optimisations for sexually transmitted infections (STIs). In this Review, we aim to highlight urgent needs in global STI management, including: (1) improved surveillance to monitor antimicrobial r...

Renewed interest in developing vaccines against Neisseria gonorrhoeae has been sparked by the increasing threat of gonococcal antimicrobial resistance (AMR) and growing optimism that gonococcal vaccines are biologically feasible. Evidence suggests serogroup B Neisseria meningitidis vaccines might provide some cross-protection against N. gonorrhoeae...

The bacterium Neisseria gonorrhoeae causes the sexually transmitted infection (STI) gonorrhoea, which has an estimated global annual incidence of 86.9 million adults. Gonorrhoea can present as urethritis in men, cervicitis or urethritis in women, and in extragenital sites (pharynx, rectum, conjunctiva and, rarely, systemically) in both sexes. Confi...

A prospective multicenter clinical study involving subjects from 21 sites across the United States was conducted to validate the performance of a new in vitro diagnostic nucleic acid amplification test (NAAT) for the detection of Mycoplasma genitalium . Seven urogenital specimen types (N = 11,556) obtained from 1,778 females ages 15-74 years and 1,...

Gonorrhea remains a major public health challenge and current recommendations for gonorrhea treatment are threatened by evolving antimicrobial resistance and a diminished pipeline for new antibiotics. Evaluations of potential new treatments for gonorrhea currently make limited use of new understanding of the pharmacokinetics/pharmacodynamics contri...

Data from mathematical models suggest that kissing and saliva exchange during sexual activity might be major contributors to community gonorrhoea morbidity. Although there is little evidence to support this, it provokes discussion of the potential role of the oropharynx in gonorrhoea control. Improved sensitivity and ease of diagnostic testing, as...

Background Symptom awareness, behavioral factors, and other barriers associated with timely sexually transmitted infection (STI) health care provision in men is not well studied. Methods Men attending an STI clinic answered a questionnaire regarding their symptoms, sexual behavior, and sociodemographic and behavioral characteristics. Characteristi...

Background We evaluated single oral dose of delafloxacin versus single intramuscular ceftriaxone in participants with uncomplicated urogenital gonorrhea (primary objective). Secondary objectives included the efficacy, safety, and tolerability of delafloxacin versus ceftriaxone for uncomplicated urogenital, rectal, and/or pharyngeal gonorrhea. Meth...

Since 1979, the National Network of STD Clinical Prevention Training Centers (NNPTC) has provided state-of-the-art clinical and laboratory training for sexually transmitted disease (STD) prevention across the United States. This article provides an overview of the history and activities of the NNPTC from its inception to present day, and emphasizes...

We evaluated microbiological correlates of successful treatment of Neisseria gonorrhoeae isolates from a Phase 2 study of gepotidacin, a novel triazaacenaphthylene antibacterial, for therapy of uncomplicated urogenital gonorrhea. Culture, susceptibility testing, genotypic characterization, and frequency of resistance (FoR) were performed for select...

Background Antibiotic-resistant Neisseria gonorrhoeae has prompted the development of new therapies. Zoliflodacin is a new antibiotic that inhibits DNA biosynthesis. In this multicenter, phase 2 trial, zoliflodacin was evaluated for the treatment of uncomplicated gonorrhea. Methods We randomly assigned eligible men and women who had signs or sympt...

Objectives Infections due to Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are among the most common bacterial sexually transmitted infections worldwide, most of which are asymptomatic. Detection of infection using a variety of specimen types in symptomatic and asymptomatic subjects is important to effectively combat CT/NG infections. T...

Background: Mycoplasma genitalium (MG) is a sexually transmitted pathogen associated with inflammatory syndromes in men and women. Macrolides and fluoroquinolones are recommended MG treatments. The frequency of MG strains with macrolide resistance-associated mutations (MRMs) and quinolone resistance-associated mutations (QRMs) is increasing worldw...

Background: Progressively decreasing susceptibility of Neisseria gonorrhoeae to the antibiotics recommended for treatment has raised concerns about the public health threat of antibiotic resistant gonorrhea. This is not a new process and the organism has reliably developed resistance to all modern antibiotics used for treatment since the dawn of t...

Objective: The aim of this study was to assess the general and sexual health of long-haul truck drivers in the United States. Methods: Drivers were recruited from company sites and truck stops in North Carolina, Tennessee, and Mississippi. A sample of 266 drivers was assessed for lifestyle activities; body mass index and blood pressure were meas...

To evaluate self-reported symptoms to guide urethritis diagnosis, symptomatic men being evaluated for urethritis were asked about 7 symptoms captured during history taking. Discharge and dysuria were significantly associated with urethritis and, when combined with genital irritation and itching, identified 95% of urethritis cases; odor and urinary...

Additional information from the Gonococcal Isolate Surveillance Project, United States, 2005–2013.

This study compared sexual risk behaviors and sexually transmitted infection prevalence among African American women who have sex with women, women who have sex with men with a single male partner, women who have sex with men with 4 or more male partners, and women who have sex with women and men at a sexually transmitted disease clinic. The result...

Emilie Alirol and colleagues discuss the development of new treatments for gonorrhea.

Analysis of prescribing (using IMS data) and gonococcal susceptibility (using GISP data)

Introduction Current CDC guidelines recommend screening “at least annually” for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) at sites of exposure using nucleic acid amplification tests (NAAT) in HIV-infected MSM. National screening rates remain suboptimal in this high-risk population, particularly at extra-genital sites. Methods We en...

Introduction To what degree population-level antibiotic use contributes to Neisseria gonorrhoeae (NG) resistance in the US is unclear. We investigated whether outpatient prescribing is associated with NG antibiotic susceptibility. Methods Using data from the Gonococcal Isolate Surveillance Project (GISP; a US surveillance system that samples male...

Urethral swabs are the test of choice for point-of-care Gram stain testing to diagnose Neisseria gonorrhoeae (NG) and non-gonococcal urethritis (NGU) in men. As an alternative to urethral swabs, meatal swabs have been recommended for collection of urethral discharge to diagnose NG and Chlamydia trachomatis (CT) in certain populations by nucleic aci...

Sexual health is considered to be a state of wellness with physical, emotional, mental, and social dimensions. Sexual health can contribute to our overall well-being in each of these dimensions. However, despite the intrinsic importance and positive aspects of sexuality in our lives, the United States presently faces significant challenges related...

Background: Chlamydia trachomatis infection is highly prevalent among young women in the United States. Prevention of long-term sequelae of infection, including tubal factor infertility, is a primary goal of chlamydia screening and treatment activities. However, the population-attributable fraction of tubal factor infertility associated with chlam...

Background: High rates of failure to qualify for clinical trial participation increase time and cost required for study completion. Identification of remediable reasons for prescreen failure can help reduce prescreen failure rates and improve study cost effectiveness. Methods: Reasons for prescreen failure to qualify for participation in a phase...

Objectives: Increased sexual partner numbers may contribute to sexually transmitted infection (STI) risk for some but not all women. This study compared women reporting having four or more partners during the preceding year (multiple partnership group) with those reporting having one partner (single partnership group) with regard to sexually risky...

The Aptima Combo2 (AC2) and Aptima CT (ACT) (Hologic Inc., San Diego, CA) are nucleic acid amplified tests (NAATs) that detect Chlamydia trachomatis (CT). AC2 also detects Neisseria gonorrhoeae (NG). Storage and temperature conditions may impact the utility of NAATs in some settings and screening programs. We evaluated specimen stability for use be...

The BD MAX™ CT/GC/TV (MAX) assay is a true multiplex assay for simultaneous detection of chlamydia (CT), gonorrhea (GC) and trichomonas (TV). We evaluated the assay performance for women using endocervical and vaginal swabs as well as urine specimens. 1143 women were tested for CT/GC and TV and, subsequently another 847 (1990 total women) for CT/GC...

Genital herpes, one of the most prevalent sexually transmitted infections (STIs) in the United States, is caused either by herpes simplex virus (HSV) type 2 (HSV-2), a virus that almost exclusively causes genital infections, or increasingly by HSV type 1 (HSV-1), a closely related virus that causes both oro-labial herpes (“cold sores”) and genital...

Syphilis is a chronic bacterial infection caused by Treponema pallidum that is endemic in low-income countries and and occurs at lower rates in middle-income and high-income countries. The disease is of both individual and public health importance and, in addition to its direct morbidity, increases risk of HIV infection and can cause lifelong morbi...

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...

Chlamydia trachomatis/Neisseria gonorrhoeae assay performance in males is typically determined using post-swab urine, though pre-swab urine is used in practice. We collected swabs and urine from men and used the Cepheid Xpert® CT/NG sample adequacy control to determine the effect of swab collection on urine cellular content. No difference was obser...

Resumen: El Sur Este de los Estados Unidos tiene tasas altas de visitas a iglesias y de infección por VIH. Evaluamos la relación entre visitas a iglesias y viremia por VIH en una cohorte de pacientes infectados con VIH en el Sur Este de los EEUU. La viremia (carga viral ≥ 200 copias/ml) fue analizada a los 12 meses de iniciar el cuidado médico. Lo...

Problem/condition: Gonorrhea is the second most commonly reported notifiable disease in the United States; 350,062 gonorrhea cases were reported in 2014. Sexually transmitted infections caused by Neisseria gonorrhoeae are a cause of pelvic inflammatory disease in women, which can lead to serious reproductive complications including tubal infertili...

Sexually transmitted infections (STIs) comprise more than 30 different bacterial, viral, protozoal, and yeast infections acquired during sexual intercourse and therefore directly afflicting the genital tracts or gaining systemic access across the genital mucosae. Effective vaccines have been developed against only two viral STIs (hepatitis B and hu...

Reproductive and sexual health morbidity in the United States is much higher than that of other developed nations. It is estimated that in the United States, there are 50,000 new human immunodeficiency virus infections, 20 million sexually transmitted infections (STIs), 3 million unintended pregnancies, and 1 million rapes each year. The annual cos...

The objective of this study was to evaluate whether nondisclosure or selective disclosure of HIV status to others is associated with retention in HIV care. This retrospective analysis evaluated the relationship of self-reported disclosure of HIV status as an indicator for poor retention in care (a gap in care >180 days) during the 12 months followi...

This study describes gonococcal cephalosporin susceptibility trends using 2006-2014 data from the US Centers for Disease Control and Prevention (CDC) Gonococcal Isolate Surveillance Project and changes in gonorrhea treatment following publication in 2012 of a CDC treatment guideline update.Gonorrhea is a common sexually transmitted disease that, if...

Little is known about whether Chlamydia trachomatis can be sexually transmitted between women or how often it occurs in women who have sex with women. We investigated Chlamydia trachomatis prevalence and serum Chlamydia trachomatis-specific antibody responses among African American women who have sex with women who reported a lifetime history of se...

We evaluated the BD Viper LT System for detection of Chlamydia trachomatis and Neisseria gonorrhoeae using samples collected from symptomatic patients that included urine, vaginal swabs, and cervical samples in liquid-based cytology media. Results were compared with those obtained using the BD Viper XTR platform. The positive and negative percent a...

Background Surveillance for gonococcal (GC) antimicrobial resistance is focused on susceptibilities of urogenital GC isolates. The ability of surveillance programs utilising only urogenital specimens to detect resistance in communitites could theoretically be compromised if extragenital (i.e. pharyngeal or rectal) GC infectons were more often resis...

Introduction Diagnosis of anogenital herpes is definitively established by testing anogenital lesion specimens from symptomatic patients by culture or molecular methods. The objective of this study was to evaluate the cobas® HSV 1 and HSV 2 Test using clinician-collected swab specimens from external anogenital lesions as part of a large multicenter...

Objectives The objective of this study was to evaluate the cobas® HSV 1 and HSV 2 Test using clinician-collected swab specimens from external anogenital lesions as part of a large multicenter clinical trial. Methods Two swabs were collected from patients with possible HSV infection at 8 geographically diverse sites. The first swab was used for the...

Background The Southeastern US is characterised as America’s “bible belt” with prominent religiosity yet also has the highest HIV incidence. The interplay between religion/spirituality and HIV-related outcomes could vary from detrimental to beneficial. We previously showed that men who have sex with men (MSM) who attended church were more likely to...

Introduction Prevention of tubal factor infertility (TFI) is a primary objective of chlamydia prevention programs. This study aimed to describe TFI epidemiology in infertility clinic patients. Methods Data were analysed from one site of an ongoing two-site study. Medical record data from infertile (unable to conceive for ≥12 months, no history of t...

Background 15.5% of the population in the United States is infected with herpes simplex virus-type 2 (HSV-2). HSV-2 rates are disproportionately high in black Americans, with seroprevalence approaching 50% in some communities. Knowledge of infection status is an important prevention tool. We evaluated barriers to acceptance of serological testing f...

Background Chlamydia trachomatis (CT) and Neisseria gonorrhoea (GC) are the two most common bacterial STIs. Screening for CT and/or GC, is recommended in many countries. The prevalence of Trichomonas vaginalis (TV) is also high and negative consequences of untreated infection may be serious. Inclusion of TV as part of a combination assay would faci...

Background Previous data suggest that women who have sex with women and men (WSWM) have the highest STI risk compared to other female sexual behaviour groups. We compared risk behaviours and STI rates among women who have sex with women (WSW), WSWM, women with a single male partner (WSM), and women with multiple male partners. We hypothesised a con...

The US system for gonococcal antimicrobial susceptibility surveillance monitors trends exclusively among men with urethral infection, the population from whom the yield of gonococcal culture is highest. Little is known about the susceptibility of female urogenital isolates, and it is unclear whether gonococcal susceptibility among men who report se...

Background. Progressive resistance to antimicrobial agents has reduced options for gonorrhea therapy worldwide. Solithromycin (CEM-101) is a novel oral fluoroketolide antimicrobial with substantial in vitro activity against Neisseria gonorrhoeae. Methods. We conducted a phase 2 trial of 2 oral doses of solithromycin (1200 and 1000 mg) for treatment...

This Viewpoint discusses a framework for improving patient care and public sexual health. Reproductive and sexual health morbidity in the United States continues to far exceed that of other developed nations. Calls for greater attention and new strategies to address this fact usually begin with a ceremonial nod to the numbers of associated adverse...

Background Chlamydia, gonorrhoea and trichomonas infections remain highly prevalent with annual WHO estimates of 106, 107 and 276 million cases respectively. Screening for all 3 infections in a single assay could improve control efforts. Aim This study assessed the performance of the BD MAX ™ CT/GC/TV (BD MAX) for detection of chlamydia, gonorrho...

Epidemiologic links between chronic hepatitis C and herpes simplex type-2 infection have been suggested; however, type-specific tests for HSV-2 infection have not been validated in patients with chronic hepatitis C infection. The Focus HerpeSelect(®) HSV-2 IgG (Cypress, California) assay and the Biokit HSV-2 rapid assay (Biokit USA, Lexington, MA)...

Persons receiving effective HIV treatment experience longevity and improvement in quality of life. For those infected, social support is associated with improved medication adherence. Disclosure of infection status is likely a prerequisite for social support. However, little research describes patterns of HIV disclosure by infected persons. We retr...

Azithromycin, administered with ceftriaxone, is recommended by CDC for treatment of gonorrhea. Many experts have expressed concern about the ease with which Neisseria gonorrhoeae can acquire macrolide resistance. We sought to describe gonococcal azithromycin susceptibility in the United States and determine whether azithromycin susceptibility has c...

Background Sexually transmissible infection (STI) history, prevalence and seroprevalence among lifetime exclusive women who have sex with women (WSW) and an age-matched group of women who have sex with women and men (WSWM) was evaluated. Methods: Participants completed a study questionnaire and had genital specimens and sera collected for STI testi...

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...

Introduction: We performed a pilot study examining the safety and tolerability of valacyclovir in veterans with herpes simplex virus type 2 and hepatitis C virus (HCV) coinfection. Methods: We performed a randomized double-blind, placebo-controlled, crossover clinical trial in U.S. veterans with genotype 1 HCV/herpes simplex virus type 2 coinfec...

In the absence of antiretroviral therapy, valacyclovir may reduce HIV viral load and increase CD4+ T-lymphocyte count. We sought to evaluate the impact of valacyclovir on HIV and HSV-2 in co-infected patients receiving antiretroviral therapy with previously unrecognised HSV-2 infection. A prospective, randomised-controlled, 24-week trial of valacyc...

Background: Ceftriaxone is the foundation of currently recommended gonorrhea treatment. There is an urgent need for backup treatment options for patients with cephalosporin allergy or infections due to suspected cephalosporin-resistant Neisseria gonorrhoeae. We evaluated the efficacy and tolerability of 2 combinations of existing noncephalosporin...

BACKGROUND: Emerging gonococcal cephalosporin resistance is an urgent public health threat. Gonococcal cefixime minimum inhibitory concentrations (MICs) increased in the US during 2006-2010; the largest increases were observed in the West and among men who have sex with men (MSM). In response, CDC updated its treatment recommendations in 2012 and n...

Methods • Data were drawn from the Gonococcal Isolate Surveillance Project (GISP) • GISP is a CDC-supported sentinel surveillance system that has monitored N. gonorrhoeae antimicrobial susceptibility since 1987. • Each month, isolates are collected from up to 25 men with gonococcal urethritis consecutively presenting to each participating sexually...