David L. Trees

Etiology of Genital Ulcers and Prevalence of Human Immunodeficiency Virus Coinfection in 10 US Cities

To determine the etiology of genital ulcers and to assess the prevalence of human immunodeficiency virus (HIV) infection in ulcer patients in 10 US cities, ulcer and serum specimens were collected from approximately 50 ulcer patients at a sexually transmitted disease clinic in each city. Ulcer specimens were tested using a multiplex polymerase chain reaction assay to detect Haemophilus ducreyi, Treponema pallidum, and herpes simplex virus (HSV); sera were tested for antibody to HIV. H. ducreyi was detected in ulcer specimens from patients in Memphis (20% of specimens) and Chicago (12%). T. pallidum was detected in ulcer specimens from every city except Los Angeles (median, 9% of specimens; range, 0%-46%). HSV was detected in >/=50% of specimens from all cities except Memphis (42%). HIV seroprevalence in ulcer patients was 6% (range by city, 0%-18%). These data suggest that chancroid is prevalent in some US cities and that persons with genital ulcers should be a focus of HIV prevention activities.

Molecular epidemiology of Neisseria gonorrhoeae exhibiting decreased susceptibility and resistance to ciprofloxacin in Hawaii, 1991-1999

Background Clinically significant resistance to Centers for Disease Control and Prevention (CDC)-recommended doses of fluoroquinolones (ciprofloxacin and ofloxacin) has been reported for Neisseria gonorrhoeae. In Hawaii, fluoroquinolone-resistant gonococcal isolates were first identified in 1991. Goal To assess the diversity, based on phenotypic and genotypic characterization, of gonococcal isolates exhibiting decreased susceptibility (CipI; MICs = 0.125–0.5 &mgr;g/ml) or clinically significant resistance (CipR; MICs ≥ 1 &mgr;g/ml) to ciprofloxacin in Hawaii from 1991 through 1999. Study Design Antimicrobial susceptibilities, auxotype/serovar (A/S) class, GyrA/ParC alteration patterns, and plasmid profiles were determined for gonococci isolated in Honolulu from 1991 through 1999 that exhibited intermediate or clinically significant resistance to ciprofloxacin. Strain phenotypes were defined by A/S class, GyrA/ParC alteration pattern, and penicillin–tetracycline resistance phenotype supplemented with plasmid profiles for &bgr;-lactamase–producing isolates. Results Altogether, 68 isolates exhibiting intermediate or clinically significant resistance to ciprofloxacin belonged to 23 and 19 strain phenotypes, respectively. Among the CipI and CipR isolates, 4 and 13 GyrA/ParC alterations patterns were identified, respectively. The 91,95/Asp-86 alteration pattern occurred most frequently among CipR isolates. Forty-four strain phenotypes were represented by only one isolate. In addition, seven pairs and two clusters of isolates were identified. Conclusions From 1991 through 1997, few gonococcal strains exhibiting intermediate or clinically significant resistance to CDC-recommended doses of fluoroquinolones were identified from Hawaii. Isolates belonged to a large number of phenotypic and genotypic types, suggesting that most cases were imported, with only a few instances in which isolate pairs indicated that secondary transmission of infections had occurred in Hawaii. Beginning in 1998, the number of CipR isolates increased markedly, and more isolates belonged to fewer phenotypic and genotypic types, suggesting either more frequent importation of fewer strain types or the possibility that the endemic spread of a few strains is beginning to occur.

The emergence of Neisseria gonorrhoeae with decreased susceptibility to Azithromycin in Kansas City, Missouri, 1999 to 2000.

Background and Objectives We describe the first cluster of persons with Neisseria gonorrhoeae with decreased susceptibility to azithromycin (AziDS; minimum inhibitory concentration ≥1.0 &mgr;g/mL) in the United States. Goal The goal of this study was to identify risk factors for AziDS N. gonorrhoeae and to describe isolate microbiology. Study Design Persons with AziDS N. gonorrhoeae (cases) were identified in Kansas City, Missouri, through the Gonococcal Isolate Surveillance Project (GISP) in 1999 and expanded surveillance, January 2000 to June 2001. A case-control study using 1999 GISP participants was conducted; control subjects had azithromycin-susceptible N. gonorrhoeae. Results Thirty-three persons with AziDS N. gonorrhoeae were identified. Case patients were older than control patients (median age, 33 years vs. 23 years; P <0.001). Fifty percent of cases and 13% of control subjects had a history of sex with a female commercial sex worker (odds ratio, 7.0; 95% confidence interval, 1.3–36.0); 50% of cases and 4% of control subjects met sex partners on street A (P <0.01). AziDS N. gonorrhoeae isolates were phenotypically and genotypically similar and contained an mtrR gene mutation. Conclusions With few treatment options remaining, surveillance for antimicrobial-resistant N. gonorrhoeae is increasingly important, especially among persons at high risk.

Fluoroquinolone resistance among Neisseria gonorrhoeae isolates in Hawaii, 1990-2000: role of foreign importation and increasing endemic spread.

Objectives: In 1999, an increase in ciprofloxacin-resistant Neisseria gonorrhoeae isolates was identified in Hawaii, prompting initiation of investigative studies. Goals: The goal of this study was epidemiologic evaluation of this increase. Study: The authors conducted a review of laboratory data; case-series and case-control studies based on medical record review; and a prospective case-control study based on patient interviews. Results: A total of 10.4% (21 of 201) of gonococcal isolates from Hawaii in 2000 were ciprofloxacin-resistant compared with <1.5% per year from 1990 to 1997. From medical record review for patients diagnosed with ciprofloxacin-resistant N. gonorrhoeae infection from 1990 to 1999, 59% were Asian/Pacific Islanders and 91% were heterosexual. From review of 1998 and 1999 sexually transmitted disease (STD) clinic medical records, patients with ciprofloxacin-resistant N. gonorrhoeae were more likely to report recent foreign travel or a sex partner with recent foreign travel than patients with ciprofloxacin-susceptible N. gonorrhoeae (6 of 12 vs. 10 of 117, P <0.001), but 50% (6 of 12) acquired a ciprofloxacin-resistant strain locally from a partner with no recent travel. In 2000, 70% (7 of 10) of STD clinic patients with ciprofloxacin-resistant N. gonorrhoeae acquired their infection locally from partners with no reported recent travel. Conclusions: Infections with ciprofloxacin-resistant N. gonorrhoeae are increasing and evolving in Hawaii.

Azithromycin Resistance and Decreased Ceftriaxone Susceptibility in Neisseria gonorrhoeae, Hawaii, USA

During 2016, eight Neisseria gonorrhoeae isolates from 7 patients in Hawaii were resistant to azithromycin; 5 had decreased in vitro susceptibility to ceftriaxone. Genomic analysis demonstrated a distinct phylogenetic clade when compared with local contemporary strains. Continued evolution and widespread transmission of these strains might challenge the effectiveness of current therapeutic options.

Syphilis in Atlanta during an era of declining incidence.

Background: Syphilis transmission in Atlanta is ongoing despite declining incidence. Objectives: To identify risk factors and missed opportunities for prevention. Study Design: A case‐control study design was used. Twenty‐five sexually transmitted disease (STD) clinic patients with primary or secondary syphilis by polymerase chain reaction and serology and 49 matched controls were interviewed. Results: Persons with syphilis more frequently had HIV infection (24% versus 2%; P = 0.005), crack‐using sex partners (52% versus 18%; odds ratio [OR] = 5.1; 95% CI = 1.7‐15.5), and a history of incarceration (80% versus 57%; OR = 3.0; CI = 1.0‐9.3). Many cases (48%) and controls (31%) had received drug‐abuse treatment. Only 40% of previously incarcerated patients and 74% of those with a history of drug treatment reported receiving STD/HIV education in those settings. Among all patients reporting recent HIV education, 41% were told about STD recognition and treatment. Unprotected sex and delay in seeking care were common. Conclusion: To prevent syphilis and associated HIV, more extensive STD education is needed in jails and drug‐treatment centers.

Large Cluster of Neisseria meningitidis Urethritis in Columbus, Ohio, 2015

BackgroundnNeisseria meningitidis (Nm) is a Gram-negative diplococcus that normally colonizes the nasopharynx and rarely infects the urogenital tract. On Gram stain of urethral exudates, Nm can be misidentified as the more common sexually transmitted pathogen Neisseria gonorrhoeae.nnnMethodsnIn response to a large increase in cases of Nm urethritis identified among men presenting for screening at a sexually transmitted disease clinic in Columbus, Ohio, we investigated the epidemiologic characteristics of men with Nm urethritis and the molecular and phylogenetic characteristics of their Nm isolates. The study was conducted between 1 January and 18 November 2015.nnnResultsnSeventy-five Nm urethritis cases were confirmed by biochemical and polymerase chain reaction testing. Men with Nm urethritis were a median age of 31 years (interquartile range [IQR] = 24-38) and had a median of 2 sex partners in the last 3 months (IQR = 1-3). Nm cases were predominantly black (81%) and heterosexual (99%). Most had urethral discharge (91%), reported oral sex with a female in the last 12 months (96%), and were treated with a ceftriaxone-based regimen (95%). A minority (15%) also had urethral chlamydia coinfection. All urethral Nm isolates were nongroupable, ST-11 clonal complex (cc11), ET-15, and clustered together phylogenetically. Urethral Nm isolates were similar by fine typing (PorA P1.5-1,10-8, PorB 2-2, FetA F3-6), except 2, which had different PorB types (2-78 and 2-52).nnnConclusionsnBetween January and November 2015, 75 urethritis cases due to a distinct Nm clade occurred among primarily black, heterosexual men in Columbus, Ohio. Future urogenital Nm infection studies should focus on pathogenesis and modes of sexual transmission.

Complete Genome Sequences of Three Neisseria gonorrhoeae Laboratory Reference Strains, Determined Using PacBio Single-Molecule Real-Time Technology

ABSTRACT Neisseria gonorrhoeae, the etiological agent that causes the sexually transmitted infection gonorrhea, is a significant public health concern due to the emergence of antimicrobial resistance. We report the complete genome sequences of three reference isolates with varied antimicrobial susceptibility that will aid in elucidating the genetic mechanisms that confer resistance.

Antimicrobial Resistance to Sexually Transmitted Infections

According to the World Health Organization (WHO), “Sexually transmitted infections are a major global cause of acute illness, infertility, disability and death with severe medical and psychological economic consequences for millions of men, women, and infants.” (World Health Organization, 2001). In 1999 WHO estimated that 340 million curable sexually transmitted infections (STIs) occurred throughout the world in men and women aged 15–49 years: new cases of syphilis, gonorrhea, chlamydia, and trichomonas. This estimate did not account for the millions of new cases of viral sexually transmitted infections such as human papillomavirus and herpes. In the United States, sexually transmitted infections are among the most common notifiable diseases (Centers for Disease Control and Prevention, 2006d). The Centers for Disease Control and Prevention (CDC) estimated that in 2000, 18.9 million new sexually transmitted infections occurred in the United States in that year alone (Weinstock et al., 2004). A report by the Institute of Medicine indicated that the scope of the sexually transmitted diseases (STD) epidemic is largely hidden from the American public despite its tremendous cost in health and economic terms (Institute of Medicine, 1997). Major advances have been made in the clinical recognition, diagnosis, and treatment of many STI. Sensitive and specific assays have become available for noninvasive diagnosis of specific infections. New agents have advanced the treatment of these infections. However, resistance remains a continual challenge, especially, for the treatment and prevention of some STIs. In this chapter, we review the development of antimicrobial resistance among several STIs and discuss the prevalence and mechanisms of resistance along with recommendations for treatment.

Genomic sequencing of Neisseria gonorrhoeae to respond to the urgent threat of antimicrobial-resistant gonorrhea

The development of resistance of Neisseria gonorrhoeae to available first-line antibiotics, including penicillins, tetracyclines, fluoroquinolones and cephalosporins, has led to the circulation of multidrug-resistant gonorrhea at a global scale. Advancements in high-throughput whole-genome sequencing (WGS) provide useful tools that can be used to enhance gonococcal detection, treatment and management capabilities, which will ultimately aid in the control of antimicrobial resistant gonorrhea worldwide. In this minireview, we discuss the application of WGS of N. gonorrhoeae to strain typing, phylogenomic, molecular surveillance and transmission studies. We also examine the application of WGS analyses to the public health sector as well as the potential usage of WGS-based transcriptomic and epigenetic methods to identify novel gonococcal resistance mechanisms.