Early syphilis in Guangzhou, China: presentation, molecular detection of Treponema pallidum , and genomic sequences in clinical specimens and isolates obtained by rabbit infectivity testing.

Background: The global resurgence of syphilis requires novel prevention strategies. Whole genome sequencing (WGS) of Treponema pallidum ( TPA ) using different specimen types is essential for vaccine development. Methods: Patients with primary (PS) and secondary (SS) syphilis were recruited in Guangzhou, China. We collected ulcer exudates and blood from PS participants, and skin biopsies and blood from SS participants for TPA polA polymerase chain reaction (PCR); ulcer exudates and blood were also used to isolate TPA strains by rabbit infectivity testing (RIT). TPA WGS was performed on 52 ulcer exudates and biopsy specimens and 25 matched rabbit isolates. Results: We enrolled 18 PS and 51 SS participants from December 2019 to March 2022. Among PS participants, TPA DNA was detected in 16 (89%) ulcer exudates and three (17%) blood specimens. Among SS participants, TPA DNA was detected in 50 (98%) skin biopsies and 27 (53%) blood specimens. TP A was isolated from 48 rabbits, with a 71% (12/17) success rate from ulcer exudates and 69% (36/52) from SS bloods. Twenty-three matched SS14 clade genomes were virtually identical, while two Nichols clade pairs had discordant tprK sequences. Forty-two of 52 unique TPA genomes clustered in an SS14 East Asia subgroup, while ten fell into two East Asian Nichols subgroups. Conclusions: Our TPA detection rate was high from PS ulcer exudates and SS skin biopsies and over 50% from SS whole blood, with RIT isolation in over two-thirds of samples. Our results support the use of WGS from rabbit isolates to inform vaccine development. Summary: We performed Treponema pallidum molecular detection and genome sequencing from multiple specimens collected from early syphilis patients and isolates obtained by rabbit inoculation. Our results support the use of whole genome sequencing from rabbit isolates to inform syphilis vaccine development.

Diagnosis and Management of Trichomonas vaginalis: Summary of Evidence Reviewed for the 2021 Centers for Disease Control and Prevention Sexually Transmitted Infections Treatment Guidelines.

Trichomonas vaginalis is likely the most prevalent nonviral sexually transmitted infection, affecting an estimated 3.7 million women and men in the United States. Health disparities are prominent in the epidemiology of trichomoniasis, as African Americans are >4 times more likely to be infected than persons of other races. Since publication of the 2015 Centers for Disease Control and Prevention sexually transmitted diseases treatment guidelines, additional data have bolstered the importance of T. vaginalis infection sequelae in women, including increased risk of human immunodeficiency virus (HIV) acquisition, cervical cancer, preterm birth, and other adverse pregnancy outcomes. Less is known about the clinical significance of infection in men. Newly available diagnostic methods, including point-of-care assays and multiple nucleic acid amplification tests, can be performed on a variety of genital specimens in women and men, including urine, allowing more accurate and convenient testing and screening of those at risk for infection. Repeat and persistent infections are common in women; thus, rescreening at 3 months after treatment is recommended. In vitro antibiotic resistance to 5-nitroimidazole in T. vaginalis remains low (4.3%) but should be monitored. High rates of T. vaginalis among sexual partners of infected persons suggest a role for expedited partner treatment. A randomized controlled trial in HIV-uninfected women demonstrated that multidose metronidazole 500 mg twice daily for 7 days reduced the proportion of women with Trichomonas infection at 1 month test of cure compared with women receiving single-dose therapy (2 g). The 2-g single-dose oral metronidazole regimen remains the preferred treatment in men.

Intersection of Syphilis and Human Immunodeficiency Virus (HIV) Networks to Identify Opportunities to Enhance HIV Prevention.

BACKGROUND: Human immunodeficiency virus (HIV) and syphilis infection continue at disproportionate rates among minority men who have sex with men (MSM) in the United States. The integration of HIV genetic clustering with partner services can provide important insight into local epidemic trends to guide interventions and control efforts. METHODS: We evaluated contact networks of index persons defined as minority men and transgender women diagnosed with early syphilis and/or HIV infection between 2018 and 2020 in 2 North Carolina regions. HIV clusters were constructed from pol sequences collected through statewide surveillance. A combined "HIV-risk" network, which included persons with any links (genetic or sexual contact) to HIV-positive persons, was evaluated by component size, demographic factors, and HIV viral suppression. RESULTS: In total, 1289 index persons were identified and 55% named 1153 contacts. Most index persons were Black (88%) and young (median age 30 years); 70% had early syphilis and 43% had prevalent HIV infection. Most people with HIV (65%) appeared in an HIV cluster. The combined HIV-risk network (1590 contact network and 1500 cluster members) included 287 distinct components; however, 1586 (51%) were in a single component. Fifty-five percent of network members with HIV had no evidence of viral suppression. Overall, fewer index persons needed to be interviewed to identify 1 HIV-positive member without viral suppression (1.3 vs 4.0 for contact tracing). CONCLUSIONS: Integration of HIV clusters and viral loads illuminate networks with high HIV prevalence, indicating recent and ongoing transmission. Interventions intensified toward these networks may efficiently reach persons for HIV prevention and care re-engagement.

Screening Veterans for Syphilis: Implementation of the Reverse Sequence Algorithm.

We evaluated the syphilis reverse sequence algorithm (RSA) in a Veteran Affairs facility, finding 5.5% reactive Treponema pallidum enzyme immunoassay (EIA) tests. In a subset of EIA+/VDRL-/TP-PA+ cases, 48% were previously treated. Of veterans with unknown/no prior therapy, only 45% had documentation of subsequent treatment, suggesting suboptimal interpretation of RSA results.

Home Screening for Bacterial Vaginosis to Prevent Sexually Transmitted Diseases.

BACKGROUND: Longitudinal studies have consistently found a significant association between bacterial vaginosis (BV) and acquisition of sexually transmitted diseases. However, there are limited prospective data to confirm these findings. METHODS: We conducted a prospective, randomized, open-label trial of home screening and treatment of young women with asymptomatic BV who were also at high risk for sexually transmitted diseases. These women were screened every 2 months for 12 months and randomized to treatment with oral metronidazole 500 mg twice daily for 7 days or observation alone. The primary outcome was the incidence of gonorrhea and/or chlamydia. RESULTS: A total of 1365 subjects were enrolled in the study across 10 sites. Adherence with mailing specimens obtained at home was excellent in both groups (84%-88%). The incidence of gonorrhea and/or chlamydia was 19.1 per 100 person-years (95% confidence interval, 15.1-22.1) for the treatment group and 18.5 per 100 person-years (15.1-22.8) for the observation arm, a difference that was not statistically significant. CONCLUSIONS: Young women were very amenable to home screening for BV, gonorrhea, and chlamydia. Treatment of asymptomatic BV with 1 week of oral metronidazole did not decrease the incidence of gonorrhea and/or chlamydia. CLINICAL TRIALS REGISTRATION: NCT00667368.

Advances in the Understanding and Treatment of Male Urethritis.

Neisseria gonorrhoeae and Chlamydia trachomatis are well-documented urethral pathogens, and the literature supporting Mycoplasma genitalium as an etiology of urethritis is growing. Trichomonas vaginalis and viral pathogens (herpes simplex virus types 1 and 2 and adenovirus) can cause urethritis, particularly in specific subpopulations. New data are emerging regarding the potential role of bacterial vaginosis-associated bacteria in urethritis, although results are inconsistent regarding the pathogenic role of Ureaplasma urealyticum in men. Mycoplasma hominis and Ureaplasma parvum do not appear to be pathogens. Men with suspected urethritis should undergo evaluation to confirm urethral inflammation and etiologic cause. Although nucleic acid amplification testing would detect N. gonorrhoeae and C. trachomatis (or T. vaginalis if utilized), there is no US Food and Drug Administration-approved clinical test for M. genitalium available in the United States at this time. The varied etiologies of urethritis and lack of diagnostic options for some organisms present treatment challenges in the clinical setting.

Sexual Assault and Sexually Transmitted Infections in Adults, Adolescents, and Children.

Survivors of sexual assault are at risk for acquiring sexually transmitted infections (STIs). We conducted literature reviews and invited experts to assist in updating the sexual assault section for the 2015 Centers for Disease Control and Prevention sexually transmitted diseases (STD) treatment guidelines. New recommendations for STI management among adult and adolescent sexual assault survivors include use of nucleic acid amplification tests (NAATs) for detection of Trichomonas vaginalis by vaginal swabs; NAATs for detection of Neisseria gonorrhoeae and Chlamydia trachomatis from pharyngeal and rectal specimens among patients with a history of exposure or suspected extragenital contact after sexual assault; empiric therapy for gonorrhea, chlamydia, and trichomoniasis based on updated treatment regimens; vaccinations for human papillomavirus (HPV) among previously unvaccinated patients aged 9-26 years; and consideration for human immunodeficiency virus (HIV) nonoccupational postexposure prophylaxis using an algorithm to assess the timing and characteristics of the exposure. For child sexual assault (CSA) survivors, recommendations include targeted diagnostic testing with increased use of NAATs when appropriate; routine follow-up visits within 6 months after the last known sexual abuse; and use of HPV vaccination in accordance with national immunization guidelines as a preventive measure in the post-sexual assault care setting. For CSA patients, NAATs are considered to be acceptable for identification of gonococcal and chlamydial infections from urine samples, but are not recommended for extragenital testing due to the potential detection of nongonococcal Neisseria species. Several research questions were identified regarding the prevalence, detection, and management of STI/HIV infections among adult, adolescent, and pediatric sexual assault survivors.

The footprint of old syphilis: using a reverse screening algorithm for syphilis testing in a U.S. Geographic Information Systems-Based Community Outreach Program.

The impact of syphilis reverse sequence screening has not been evaluated in community outreach. Using reverse sequence screening in neighborhoods identified with geographic information systems, we found that among 239 participants, 45 (19%) were seropositive. Of these, 3 (7%) had untreated syphilis, 33 (73%) had previously treated syphilis infection, and 9 (20%) had negative nontreponemal test results.

Hepatitis B vaccination of susceptible elderly residents of long term care facilities during a hepatitis B outbreak.

Protection of older persons, particularly those with diabetes, against hepatitis B virus (HBV) infection is of growing concern because of increased reports of outbreaks among long-term care facility residents receiving assisted blood glucose monitoring. We evaluated hepatitis B vaccine immunogenicity among residents immunized in response to two such outbreaks in skilled nursing facilities during June 2009-July 2010. One hundred forty-eight (71%) of 209 residents were found to be susceptible to HBV infection. Of 105 patients who began a vaccination series with Twinrix(®) (0-, 1-, 6-month dosing), 86 (82%) completed the series and postvaccination testing. Of these, most were elderly (median age 79.5 years; range 45-101), female (56%), and African-American (51%). Twenty-nine (34%) vaccinated residents had post-vaccination hepatitis B surface antibody levels ≥10 mIU/ml. There were no significant differences in vaccine response by age, gender, race, diabetes status, body mass index, or current smoking status. Our findings indicate that a low proportion of skilled nursing facility residents achieved a seroprotective response after hepatitis B vaccination.

Trichomonas vaginalis genital infections: progress and challenges.

Trichomonas vaginalis (TV) infection is the most prevalent curable sexually transmitted infection in the United States and worldwide. Most TV infections are asymptomatic, and the accurate diagnosis of this infection has been limited by lack of sufficiently sensitive and specific diagnostic tests, particularly for men. To provide updates for the 2010 Centers for Disease Control and Prevention's Sexually Transmitted Diseases Treatment Guidelines, a PubMed search was conducted of all TV literature published from 9 January 2004 through 24 September 2008. Approximately 175 pertinent abstracts and articles were reviewed and discussed with national experts. This article describes advances in TV diagnostics which have led to an improved understanding of the epidemiology of this pathogen, as well as potential biologic and epidemiological interactions between TV and human immunodeficiency virus (HIV). New data on treatment outcomes, metronidazole-resistant TV, management of nitroimidazole-allergic patients, frequency of recurrent TV infection following treatment, and screening considerations for TV in certain populations are also presented.

Novel Treponema pallidum serologic tests: a paradigm shift in syphilis screening for the 21st century.

The mainstay of diagnosis for Treponema pallidum infections is based on nontreponemal and treponemal serologic tests. Many new diagnostic methods for syphilis have been developed, using specific treponemal antigens and novel formats, including rapid point-of-care tests, enzyme immunoassays, and chemiluminescence assays. Although most of these newer tests are not yet cleared for use in the United States by the Food and Drug Administration, their performance and ease of automation have promoted their application for syphilis screening. Both sensitive and specific, new screening tests detect antitreponemal IgM and IgG antibodies by use of wild-type or recombinant T. pallidum antigens. However, these tests cannot distinguish between recent and remote or treated versus untreated infections. In addition, the screening tests require confirmation with nontreponemal tests. This use of treponemal tests for screening and nontreponemal serologic tests as confirmatory tests is a reversal of long-held practice. Clinicians need to understand the science behind these tests to use them properly in syphilis management.

Trichomonas vaginalis infection in male sexual partners: implications for diagnosis, treatment, and prevention.

BACKGROUND: Trichomonas vaginalis causes a common sexually transmitted infection (STI) in women, yet trichomoniasis in male sexual partners is not well recognized. Nucleic acid amplification tests can increase detection of T. vaginalis in men compared with culture. METHODS: We conducted a prospective, multicenter study to evaluate T. vaginalis infection among male partners of women with trichomoniasis and factors associated with infection by recruiting patients from 3 public clinics in the United States. Male partners were tested for concordant T. vaginalis infection, defined as a positive urethral culture, urine culture, or urine polymerase chain reaction (PCR) result. A subset of men also provided a semen sample for T. vaginalis culture and PCR. Factors associated with concordant infection were determined from bivariable and multivariable analyses. RESULTS: We enrolled 540 women with trichomoniasis (diagnosed using wet mount microscopy and/or culture) and 261 (48.4%) of their male partners. T. vaginalis infection was detected in 177 (71.7%) of 256 male partners (95% confidence interval [CI], 66.0%-77.3%), of whom 136 (77.3%) were asymptomatic. A vaginal pH of >4.5 in a woman was independently associated with infection in the male partner (adjusted odds ratio, 2.5; 95% CI, 1.0-6.3). Younger male age (20-29 and 30-39 years) was also found to be an independent risk factor for concordant trichomoniasis. CONCLUSIONS: The majority of male partners of women with trichomoniasis were infected; however, few factors predicted infection. T. vaginalis causes a highly prevalent STI, necessitating vastly improved partner management, application of sensitive nucleic-acid based testing, and better clinical recognition.

Molecular subtyping of Treponema pallidum from North and South Carolina.

Patients from five clinics in North and South Carolina who had lesions suggestive of primary or secondary syphilis were evaluated using molecular techniques that allow the differentiation of Treponema pallidum strains on the basis of two variable genes, tpr and arp. Lesion samples were screened for the presence of T. pallidum DNA using PCR for polA, which represents a segment of the polymerase I gene that is unique to the spirochete. Twenty-seven of 154 lesion samples were found to contain T. pallidum, 23 of which had typeable DNA. Seven molecular subtypes were found (10f, 12f, 13f, 14f, 14g, 15f, and 16f); one to four subtypes were identified at each clinic. Subtype 14f was found in 52% of the typeable specimens and was distributed in four of the five clinics. Subtype 16f was found in 22% of specimens and was concentrated at one clinic. Further data are needed to define the role of this technique in examining the epidemiology of syphilis.

Targeted screening for Trichomonas vaginalis with culture using a two-step method in women presenting for STD evaluation.

OBJECTIVES: Trichomonas vaginalis is the most common nonviral sexually transmitted pathogen. Wet mount microscopy performs poorly compared with culture; however, universal screening using culture would be cost-prohibitive. GOAL: The goal of this study was to develop a predictive model for wet mount-negative women who may benefit from targeted use of culture for T. vaginalis detection. STUDY: Women presenting for sexually transmitted disease evaluation were prospectively screened for trichomoniasis using wet mount and culture. Multivariate logistic regression was used to identify predictors of culture-proven trichomoniasis among wet mount-negative women. RESULTS: A total of 2194 women were screened for trichomoniasis; overall, the prevalence of T. vaginalis was 17.5%. Three predictors (any drug use, contact to trichomoniasis, and African-American race) provided the most specific model (100%); any 1 predictor, the most sensitive model (97.8%). CONCLUSIONS: Given the public health impact of trichomoniasis, we recommend using any 1 of 3 predictors to identify women who would benefit from targeted culture for T. vaginalis.