Doxycycline Post-Exposure Prophylaxis for Bacterial Sexually Transmitted Infections: The Current Landscape and Future Directions.

PURPOSE OF REVIEW: The incidence of bacterial sexually transmitted infections (STI) continues to rise particularly among men who have sex with men (MSM). Doxycycline post-exposure prophylaxis (doxy-PEP) has emerged as a promising biomedical prevention strategy. This review aims to summarize the results of recent studies, highlight the current normative guidance on the use of doxy-PEP, and discuss remaining questions. RECENT FINDINGS: In the past decade, there have been four randomized controlled trials and three real-world analyses of doxy-PEP, which consistently demonstrated a reduction in Chlamydia trachomatis and Treponema pallidum infections among MSM. Questions remain regarding the efficacy of doxy-PEP for Neisseria gonorrhoeae infection and among cisgender women. Possible detrimental impacts include an increase in antimicrobial resistance as well as alterations to the gut microbiome Doxy-PEP is an effective strategy for preventing Chlamydia trachomatis and Treponema pallidum among MSM. Further work is needed to investigate the benefits among other populations, as well as to monitor for adverse effects.

A Position Statement on Mpox as a Sexually Transmitted Disease.

The global outbreak of mpox virus constituted an international public health emergency. Reports have highlighted (1) a temporal association between sexual activity and mpox, (2) an association between specific sexual practices and location of lesion development, (3) a high frequency of sexual practices conferring risk for other sexually transmitted infections among cases of mpox, (4) that mpox virus can be isolated from sexual fluids, (4) that isolated virus is infectious, and (5) a high frequency of anogenital lesions prior to disease dissemination suggesting direct inoculation during sexual activities. Finally, a growing body of evidence suggests that sexual transmission is the predominant mode of transmission for mpox virus. We therefore conclude that mpox is a sexually transmitted disease. Labeling it as such will help focus public health interventions, such as vaccinations, testing, and treatment, as well as facilitate focused awareness and education programs toward behavioral modifications to reduce exposures.

Challenges of hepatitis B treatment in rural Sub-Saharan Africa: Treatment initiation and outcomes from a public hospital-based clinic in Kono, Sierra Leone.

Despite a high prevalence, there are few successful models for de-centralizing diagnosis and treatment of chronic hepatitis B virus (HBV) infection among rural communities in Sub-Saharan Africa. We report baseline characteristics and 1 year retention outcomes for patients enrolled in a HBV clinic integrated within chronic disease services in a rural district hospital in Sierra Leone. We conducted a retrospective cohort study of patients with HBV infection enrolled between 30 April 2019 and 30 April 2021. Patients were eligible for 1 year follow-up if enrolled before 28 February 2020. Treatment eligibility at baseline was defined as cirrhosis (diagnosed by clinical criteria of decompensated cirrhosis, ultrasonographic findings or aspartate-aminotransferase-to-platelet ratio >2) or co-infection with HIV or HCV. Retention in care was defined as a documented follow-up visit at least 1 year after enrolment. We enrolled 623 individuals in care, median age of 30 years (IQR 23-40). Of 617 patients with available data, 97 (15.7%) had cirrhosis. Treatment was indicated among 113 (18.3%) patients and initiated among 74 (65.5%). Of 39 patients eligible for 1 year follow-up on treatment at baseline, 20 (51.3%) were retained at 1 year, among whom 12 (60.0%) had documented viral suppression. Among the 232 patients not initiated on treatment eligible for 1 year follow-up, 75 (32.3%) were retained at 1 year. Although further interventions are required to improve outcomes, our findings demonstrated feasibility of retention and treatment of patients with HBV infection in a rural district in Sub-Saharan Africa, when integrated with other chronic disease services.

Laboratory validation and clinical performance of a saliva-based test for monkeypox virus.

Improved diagnostic tests and accessibility are essential for controlling the outbreak of monkeypox. We describe a saliva-based polymerase chain reaction (PCR) assay for monkeypox virus, in vitro test performance, and clinical implementation of that assay in Los Angeles, San Francisco, and Palm Springs, CA. Finally, using prespecified search terms, we conducted a systematic rapid review of PubMed and Web of Science online databases of studies reporting the performance of oral pharyngeal or saliva-based tests for the monkeypox virus. The assay showed in silico inclusivity of 100% for 97 strains of monkeypox virus, with an analytic sensitivity of 250 copies/ml, and 100% agreement compared to known positive and negative specimens. Clinical testing identified 22 cases of monkeypox among 132 individuals (16.7%), of which 16 (72.7%) reported symptoms, 4 (18.2%) without a rash at the time of testing. Of an additional 18 patients with positive lesion tests, 16 (88.9%) had positive saliva tests. Our systematic review identified six studies; 100% of tests on oropharyngeal specimens from 23 patients agreed with the PCR test result of a lesion. Saliva-based PCR tests are potential tools for case identification, and further evaluation of the performance of such tests is warranted.

Resistance-Guided Therapy for Neisseria gonorrhoeae.

Antimicrobial-resistant Neisseria gonorrhoeae infections are a threat to public health. Novel strategies for combating such resistance include the development of molecular assays to facilitate real-time prediction of antimicrobial susceptibility. Resistance to ciprofloxacin is determined by the presence of a single mutation at codon 91 of the gyrase A gene; molecular assays to guide therapy are commercially available. Resistance to cefixime is conferred via 1 of 6 critical mutations in either the mosaic penA gene or specific loci in the nonmosaic region. Resistance to ceftriaxone is conferred through mutations in 1 of 4 genes: penA, ponA, penB, and mtr; however, the ability to predict reduced susceptibility based on those genes varies by geographic region. Here, we highlight the work done toward the development of 3 such assays for ciprofloxacin, cefixime, and ceftriaxone, discuss the status of our current understanding and ongoing challenges, and suggest future directions.

Effect of Frequent SARS-CoV-2 Testing on Weekly Case Rates in Long-Term Care Facilities, Florida, USA.

We analyzed 1,292,165 SARS-CoV-2 test results from residents and employees of 361 long-term care facilities in Florida, USA. A 1% increase in testing resulted in a 0.08% reduction in cases 3 weeks after testing began. Increasing SARS-CoV-2 testing frequency is a viable tool for reducing virus transmission in these facilities.

Differing Correlates of Incident Bacterial Sexually Transmitted Infections Among a Cohort of Black Cisgender Men Who Have Sex With Men and Transgender Women Recruited in 6 US Cities (HIV Prevention Trials Network 061).

ABSTRACT: Compared with Black cisgender men who have sex with men (MSM), Black transgender women had a higher incidence of bacterial sexually transmitted infections (25.9 [11.1-46.3] vs. 9.6 [8.10-11.3] per 100 person-years), higher rates of income and housing insecurity, and condomless receptive anal intercourse. Further investigation of unique risk pathways among transgender women is critical.

A Real-World Comparison of SARS-CoV-2 Rapid Antigen Testing versus PCR Testing in Florida.

The reported sensitivity of rapid, antigen-based diagnostics for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection varies. Few studies have evaluated rapid antigen tests in real-world settings or among large populations. Beginning October 2020, Florida offered individuals presenting for SARS-CoV-2 testing PCR testing if they tested positive by the Abbott BinaxNOW COVID-19 antigen (Ag) card, were symptomatic, or required or requested PCR testing. We compared results among individuals who received both types of tests at four publicly accessible testing sites across Florida. We calculated the positive percent agreement (PPA) between the two test types by symptom status. Subsequently, we evaluated the PPA among individuals regardless of symptoms with lower cycle threshold values (<30). Overall, 18,457 individuals were tested via both methods, of which 3,153 (17.1%) were positive by PCR. The PPA for the Abbott BinaxNOW COVID-19 Ag card using the PCR comparator was 49.2% (95% confidence interval [CI], 47.4% to 50.9%). Among symptomatic individuals the PPA was 51.9% (95% CI, 49.7% to 54.0%). When restricted to positive PCR tests with a cycle threshold value of <30, regardless of symptom status, the PPA was 75.3% (95% CI, 72.8% to 77.6%). The PPA of the Abbott BinaxNOW COVID-19 Ag card compared with PCR was lower than that previously reported. Our findings may reflect the performance of the BinaxNOW antigen test in real-world settings.

Multifactorial Correlates of Incident Bacterial Sexually Transmitted Infections Among Black Men Who Have Sex With Men Recruited in 6 US Cities (HIV Prevention Trials Network 061).

BACKGROUND: Black men who have sex with men are at a disproportionate risk for sexually transmitted infections (STI). Understanding the drivers of those disparities can lead to culturally tailored interventions. We aimed to characterize the incidence and correlates of STI among Black individuals from HIV Prevention Trials Network 061, a multicity cohort study conducted from 2009 to 2011 in the United States. METHODS: We used Cox proportional hazards regression to estimate adjusted hazard ratios (aHRs) accounting for within-participant correlation over multiple follow-up visits (enrollment, 6 and 12 months). We examined correlates of incident rectal and urethral STI as well as incident syphilis. RESULTS: Among 1522 individuals, the incidences of urethral and rectal Neisseria gonorrhoeae infection were 1.0 (95% confidence interval, 0.6-1.8) and 4.6 (95% CI, 3.5-6.3) cases per 100 person-years, respectively. The incidences of urethral and rectal Chlamydia trachomatis infection were 2.5 (95% CI, 1.7-3.6) and 2.5 (95% CI, 1.7-3.7) cases per 100 person-years, respectively. The incidence of syphilis was 3.6 (95% CI, 2.7-4.9) cases per 100 person-years. Younger age was associated with increased odds of incident urethral (aHR, 5.1; 95% CI, 2.3-11.1) and rectal (aHR, 2.6; 95% CI, 1.6-4.3) STI. Diagnosis of a rectal STI at baseline (aHR, 2.3; 95% CI, 1.1-4.0) and use of saliva as lubricant (aHR, 1.7; 95% CI, 1.1-2.8) were associated with incident rectal STI. Diagnosis of syphilis at baseline was associated with incident syphilis during follow-up (aHR, 5.6; 95% CI, 2.5-12.2). CONCLUSIONS: Younger participants had the highest STI incidence. Use of saliva as lubricant may be a driver of rectal infection, which deserves further study.

Improved determination of Neisseria gonorrhoeae gyrase A genotype results in clinical specimens.

BACKGROUND: The emergence of drug-resistant Neisseria gonorrhoeae has prompted the development of rapid molecular assays designed to determine antimicrobial susceptibility. One common assay uses high-resolution melt analysis to target codon 91 of the gyrase A gene (gyrA) to predict N. gonorrhoeae susceptibility to ciprofloxacin. METHODS: We extracted DNA from remnant clinical specimens that had previously tested positive for N. gonorrhoeae using the Aptima Combo 2 for CT/NG assay (Hologic, San Diego, CA, USA). We selected DNA extracts from specimens with indeterminate, WT and mutant gyrA genotype results from a previous study using high-resolution melt analysis to detect the gyrA codon 91 mutation. We re-tested those specimens using the recently CE-marked ResistancePlus GC (beta) assay (SpeeDx, Sydney, Australia). RESULTS: Of 86 specimens with indeterminate gyrA genotypes on high-resolution melt analysis, the ResistancePlus GC (beta) assay (SpeeDx) identified 30 (35%) WT, 22 (26%) mutant and 34 (40%) indeterminate gyrA genotypes. CONCLUSIONS: The ResistancePlus GC (beta) assay showed improved N. gonorrhoeae gyrA genotype determination compared with a prior gyrA genotypic high-resolution melt assay.

A Case of Asymptomatic Syphilitic Proctitis.

The incidence of syphilis is increasing. Syphilitic proctitis involving the rectal mucosa often presents with pain on defecation, rectal bleeding, or ulceration. We present a case of asymptomatic syphilitic proctitis diagnosed upon a routine screening colonoscopy.

The Frequency of Discordant Gyrase A Genotypes Among Cases of Multiple Neisseria gonorrhoeae Infections at Different Anatomic Sites.

Gyrase A genotyping reliably predicts Neisseria gonorrhoeae susceptibility to ciprofloxacin. It is unknown whether concurrent infections at different anatomic sites harbor different susceptibility profiles. We found a 3.2% frequency of discordant gyrase A genotypes among concurrent but anatomically separate N. gonorrhoeae infections diagnosed at 2 laboratories in Los Angeles.

Venue-Based HIV-Testing: An Effective Screening Strategy for High-Risk Populations in Lima, Peru.

Venue-based testing may improve screening efforts for HIV and syphilis, thereby reducing transmission. We offered onsite rapid dual HIV and syphilis testing at venues popular among MSM and/or transgender women in Lima, Peru. We used Poisson regression to calculate adjusted prevalence ratios (aPRs) for factors associated with each infection. Most (90.4%) of the 303 participants would test more frequently if testing was available at alternative venues. New cases of HIV (69) and syphilis infection (84) were identified. HIV was associated with recent sex work (aPR 1.11; 95% CI 1.02-1.22), sex with a partner of unknown serostatus (aPR 1.18; 95% CI 1.09-1.27), exclusively receptive anal sex role (aPR 1.16; 95% CI 1.03-1.30) or versatile sex role (aPR 1.17; 95% CI 1.06-1.30) compared to insertive. Syphilis was associated with reporting role versatility (aPR = 2.69; 95% CI 1.52-5.74). Sex work venues had higher syphilis prevalence 47% versus 28% in other venues, p value = 0.012. Venue-based testing may improve case finding.

Using the genetic characteristics of Neisseria gonorrhoeae strains with decreased susceptibility to cefixime to develop a molecular assay to predict cefixime susceptibility.

BACKGROUND: In the last two decades, gonococcal strains with decreased cefixime susceptibility and cases of clinical treatment failure have been reported worldwide. Gonococcal strains with a cefixime minimum inhibitory concentration (MIC) ≥0.12 µg mL-1 are significantly more likely to fail cefixime treatment than strains with an MIC <0.12 µg mL-1. Various researchers have described the molecular characteristics of gonococcal strains with reduced cefixime susceptibility, and many have proposed critical molecular alterations that contribute to this decreased susceptibility. METHODS: A systematic review of all published articles in PubMed through 1 November 2018 was conducted that report findings on the molecular characteristics and potential mechanisms of resistance for gonococcal strains with decreased cefixime susceptibility. The findings were summarised and suggestions were made for the development of a molecular-based cefixime susceptibility assay. RESULTS: The penicillin-binding protein 2 (PBP2) encoded by the penA gene is the primary target of cefixime antimicrobial activity. Decreased cefixime susceptibility is conferred by altered penA genes with mosaic substitute sequences from other Neisseria (N.) species (identifiable by alterations at amino acid position 375-377) or by non-mosaic penA genes with at least one of the critical amino acid substitutions at positions 501, 542 and 551. Based on this review of 415 international cefixime decreased susceptible N. gonorrhoeae isolates, the estimated sensitivity for an assay detecting the aforementioned amino acid alterations would be 99.5% (413/415). CONCLUSIONS: Targeting mosaic penA and critical amino acid substitutions in non-mosaic penA are necessary and may be sufficient to produce a robust, universal molecular assay to predict cefixime susceptibility.

Coxiella burnetii Endocarditis and Meningitis, California, USA, 2017.

The epidemiology of Coxiella burnetii infection in the United States is not well characterized. We report a case-patient with C. burnetii endocarditis and meningitis. Infection was diagnosed by detecting high serologic titers for C. burnetii and confirmed by sequencing of C. burnetii 16S rRNA isolated from resected valvular tissue and PCR of cerebrospinal fluid.

Field evaluation of a smartphone-based electronic reader of rapid dual HIV and syphilis point-of-care immunoassays.

OBJECTIVE: Electronic (E) devices read and quantify lateral flow-based rapid tests, providing a novel approach to assay interpretation. We evaluated the performance of one E-reader for two dual HIV and syphilis immunoassays. METHODS: We enrolled men who have sex with men and transgender women >18 years of age seeking medical services at an STD clinic in Lima, Peru, between October 2016 and April 2017. Venous blood was tested using two dual HIV and syphilis antibody immunoassays (SD BIOLINE HIV/Syphilis Duo, Republic of Korea, and First Response HIV 1+2/Syphilis Combo, India). Reference testing included a fourth-generation ELISA for HIV antibodies and use of the Treponema pallidum particle agglutination assay for syphilis antibodies. Trained clinic staff visually inspected the immunoassay results, after which the immunoassays were read by the HRDR-200 E-reader (Cellmic, USA), an optomechanical smartphone attachment. We calculated the concordance of the E-reader with visual inspection, as well as the sensitivity of both rapid immunoassays, in detecting HIV and T. pallidum antibodies. RESULTS: On reference testing of 283 participant specimens, 34% had HIV antibodies and 46% had T. pallidum antibodies. Using First Response, the concordance of the E-reader with visual inspection was 97% (95% CI 94% to 99%) for T.pallidum and 97% (95% CI 95% to 99%) for HIV antibodies. Using SD BIOLINE, the concordance of the E-reader with visual inspection was 97% (95% CI 94% to 99%) for T. pallidum and 99% (95% CI 98% to 99%) for HIV antibodies. For both immunoassays, the sensitivity for HIV antibodies was 98% (95% CI 93% to 100%) and the sensitivity for T. pallidum antibodies was 81% (95% CI 73% to 87%). CONCLUSIONS: E-reader results correlated well with visual inspection. The sensitivities of both rapid assays were comparable with past reports. Further evaluation of the E-reader is warranted to investigate its utility in data collection, monitoring and documentation of immunoassay results.