Noah Kojima

Pre-exposure prophylaxis for HIV infection and new sexually transmitted infections among men who have sex with men.

We conducted a meta-analysis to summarize rates of sexually transmitted infections among men who have sex with men (MSM) on pre-exposure prophylaxis (PrEP) for HIV versus MSM not using PrEP. Incidence rate ratios showed that MSM using PrEP were 25.3 times more likely to acquire a Neisseria gonorrhoeae infection, 11.2 times more likely to acquire a Chlamydia trachomatis infection, and 44.6 times more likely to acquire a syphilis infection versus MSM not using PrEP.

Laboratory Evaluation of a Dual-Path Platform Assay for Rapid Point-of-Care HIV and Syphilis Testing

ABSTRACT We assessed the laboratory performance of the Chembio dual-path platform HIV-syphilis rapid immunodiagnostic test and electronic reader for detection of HIV and Treponema pallidum antibodies in 450 previously characterized serum specimens. For visual or electronic reader HIV antibody detection, the sensitivity was 100% and the specificity was 98.7%. For visual T. pallidum antibody detection, the test sensitivity was 94.7% and the specificity was 100.0%; with the electronic reader, the sensitivity was 94.7% and the specificity was 99.7%.

Intron sequences that stimulate gene expression in Arabidopsis

Key messageRelated motifs strongly increase gene expression when added to an intron located in coding sequences.AbstractMany introns greatly increase gene expression through a mechanism that remains elusive. An obstacle to understanding intron-mediated enhancement (IME) has been the difficulty of locating the specific intron sequences responsible for boosting expression because they are redundant, dispersed, and degenerate. Previously we used the IMEter algorithm in two independent ways to identify two motifs (CGATT and TTNGATYTG) that are candidates for involvement in IME in Arabidopsis. Here we show that both motifs are sufficient to increase expression. An intron that has little influence on expression was converted into one that increased mRNA accumulation 24-fold and reporter enzyme activity 40-fold relative to the intronless control by introducing 11 copies of the more active TTNGATYTG motif. This degree of stimulation is twice as large as that of the strongest of 15 natural introns previously tested in the same reporter gene. Even though the CGATT and TTNGATYTG motifs each increased expression, and CGATT matches the NGATY core of the longer motif, combining the motifs to make TTCGATTTG reduced the stimulating ability of the TTNGATYTG motif. Additional substitutions were used to test the contribution to IME of other residues in the TTNGATYTG motif. The verification that these motifs are active in IME will improve our ability to predict the stimulating ability of introns, to engineer any intron to increase expression to a desired level, and to explore the mechanism of IME by seeking factors that might interact with these sequences.

Is Emtricitabine-Tenofovir Disoproxil Fumarate Pre-exposure Prophylaxis for the Prevention of Human Immunodeficiency Virus Infection Safer Than Aspirin?

We found that Emtricitabine-Tenofovir Disoproxil Fumarate Pre-Exposure Prophylaxis for the prevention of HIV infection favorably compares to aspirin in terms of user safety.

Similarities in the Markers of Inflammation Between Men With Syphilis and Women With Increased Risk of HIV Acquisition

TO THE EDITOR—We appreciated the recent study by Masson et al that utilized multiplex bead-based enzyme-linked immunosorbent assays (MBB-ELISAs) to associate human immunodeficiency virus (HIV) seroconversionwith raisedgenital inflammatory cytokines from samples from cervicovaginal lavages from KwaZuluNatal, South Africa [1]. The authors found that several cytokines, including macrophage inflammatory protein 1B, macrophage inflammatory protein 1A, interferon gamma-induced protein 10, and interleukin 8 levels, were elevated in HIV seroconverters compared with nonconverters. We conducted a pilot study using MBB-ELISAs to simultaneously screen for 63 cytokines in sera samples collected from patients with and without syphilis in Lima, Peru. Interestingly our study found elevated levels of similar chemotactic, inflammatory, and hematopoietic cytokines to the ones seen in the study by Masson et al. We found 16 cytokines that were increased (P < .05) in 5 HIV–antibody negative, syphilis-infected (rapid plasma reagin [RPR]≥ 1:32, treponema pallidum particle agglutination assay [TPPA]positive) participants (average age: 32 ± 8.8 years) and 5 HIV–antibody negative, syphilis-negative (RPR non-reactive, TPPA-negative) participants (average age: 35.6 ± 7.9 years). Of those 16 cytokines, 11 were not previously described in the literature as being syphilis associated: interleukin 7 (P = .01), vascular endothelial growth factor D (P = .01), macrophage inflammatory protein 1B (P = .01), interferon gamma-induced protein 10 (P = .02), interleukin 12 active heterodimer (P = .02), leptin (P = .02), monocyte-specific chemokine 3 (P = .02), nerve growth factor (P = .03), eotaxin (P = .04), granulocyte macrophage colony-stimulating factor (P = .04), and platelet-derived growth factor (P = .04) [2–10]. We found increased median fluorescence intensity (MFI) values for all of the 16 cytokines in

An Update on the Global Epidemiology of Syphilis

Purpose of ReviewSyphilis continues to cause morbidity and mortality worldwide. While syphilis infection is easily identifiable and treatable, rates of syphilis infection continue to increase among select populations in high-income countries and remain at endemic levels in low- and middle-income countries.Recent FindingsWorld Health Organization recommended strategies have led to the dual elimination of mother-to-child transmission of syphilis and HIV in several countries; however, outbreaks among select populations need to be adequately addressed.SummaryContinued vigilance and investment are needed to address syphilis worldwide. The epidemiology of syphilis differs in high-, and low- and middle-income countries.

Transient aortitis documented by positron emission tomography in a case series of men and transgender women infected with syphilis

Objectives Syphilis infection persists globally contributing to preventable and treatable morbidity and mortality. How extensive early syphilis disseminates is unknown. To better understand the relationship between early syphilis infection and inflammation over time, our study enrolled six individuals recently infected with syphilis for sequential positron emission tomography (PET) scans. Methods We evaluated a case series of six individuals with high syphilis titres (two secondary, two early latent and two latent, unknown duration, but with high titre) who received sequential PET scans to assess inflammation over time and its response to treatment. Results At time of PET scan, four of the six individuals were co-infected with HIV. One of the four was not on antiretroviral therapy and three of the four were not virally suppressed (viral load of >400 copies/mL). Baseline rapid plasma reagin (RPR) titres ranged from 1:64 to 1:256 (four of the six participants had prior non-reactive RPR results). Five of the six participants had mild to intense hypermetabolic PET scan activity consistent with cervical (n=5), axillary (n=4), inguinal (n=5) and retroperitoneal (n=1) adenopathy. Mild hypermetabolic activity in the thoracic aortic wall, suggesting aortitis, was present among the same five participants and resolved within 30 days for four of the five participants and 60 days for the other participant. However, widespread lymphadenopathy remained present in PET scans up to 3 months following treatment in two participants. We did not find any abnormal PET scan activity of the central nervous system. Conclusion We found abnormal aortic wall PET scan activity suggesting aortitis to be common in a case series of patients with early syphilis. In research settings, PET scans may be a sensitive tool to monitor inflammation associated with syphilis.

Addressing concerns regarding preexposure prophylaxis meta-analysis

Exaggerated and incorrect data on negative potential outcomes of PrEP use may discourage PrEP’s consideration as an HIV prevention strategy. We need more evidence-based interventions to reduce STIs, not abandonment of a highly effective HIV prevention method. Indeed, it is critically important for HIV researchers to pursue how best to harness PrEP for the welfare of those at highest risk of HIV, while minimizing potential risks. We also need more STI prevention interventions, improved diagnostic and surveillance capacity, and increased STI funding. Scientific inquiry to estimate accurately relative STI rates among comparable groups of PrEP users and nonusers is relevant to both goals but must be carried out in a rigorous manner accounting for alternate explanations.

Drug safety evaluation of oral tenofovir disoproxil fumarate-emtricitabine for pre-exposure prophylaxis for human immunodeficiency virus infection.

ABSTRACT Introduction: Tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) are nucleoside reverse transcriptase inhibitors approved as pre-exposure prophylaxis (PrEP) against human immunodeficiency virus (HIV). Prophylactic TDF-based regimens have been shown to reduce the risk of HIV infection by 74 to 92% among participants with detectable drug levels. Adverse events observed in clinical trials include nausea, elevated creatinine and liver enzymes, and decreased bone mineral density. Areas covered: This article reviews the pharmacology, pharmacokinetics, and the safety profile of TDF and FTC used as PrEP for HIV infection. Expert opinion: TDF-FTC can have a large impact in preventing HIV infections among high risk individuals when taken daily. Although TDF-FTC is associated with adverse events, they can be minimized with clinician-guided monitoring.

Rapid Training and Implementation of the Pollock Technique, a Safe, Effective Newborn Circumcision Procedure, in a Low-Resource Setting

Male circumcision is highly protective against urinary tract infections, inflammatory conditions of the penis, sexually transmitted infections, and urogenital cancers. We aimed to reintroduce newborn male circumcision through the creation of a training program in Port-au-Prince, Haiti—an area with a considerable burden of preventable urogenital infections, sexually transmitted infections, and low circumcision rate—after an earlier study reported that a majority of Haitian medical providers were in need of and wanted newborn circumcision training. The program was conducted at the GHESKIO Health Centers, a large, non-governmental clinic offering comprehensive pediatric and adult health services. Two Haitian obstetricians and seven nurses learned circumcision procedures. On training completion, one of two obstetricians achieved surgical competence. Introduction of a newborn male circumcision training program was feasible, achieving an acceptable rate of procedural competency and high-quality services. Permanent resources now exist in Haiti to train additional providers to perform newborn male circumcisions.