Exploring the association between erythema multiforme and HIV infection: some mechanisms and implications.

Erythema multiforme (EM) is an immune-mediated mucocutaneous condition characterized by hypersensitivity reactions to antigenic stimuli from infectious agents and certain drugs. The most commonly implicated infectious agents associated with EM include herpes simplex virus (HSV) and Mycoplasma pneumoniae. Other infectious diseases reported to trigger EM include human immunodeficiency virus (HIV) infection and several opportunistic infections. However, studies focusing on EM and human immunodeficiency virus (HIV) infection are scarce. even though the incidence of EM among HIV-infected individuals have increased, the direct and indirect mechanisms that predispose HIV-infected individuals to EM are not well understood. In turn, this makes diagnosing and managing EM in HIV-infected individuals an overwhelming task. Individuals with HIV infection are prone to acquiring microorganisms known to trigger EM, such as HSV, Mycobacterium tuberculosis, Treponema pallidum, histoplasmosis, and many other infectious organisms. Although HIV is known to infect CD4 + T cells, it can also directly bind to the epithelial cells of the oral and genital mucosa, leading to a dysregulated response by CD8 + T cells against epithelial cells. HIV infection may also trigger EM directly when CD8 + T cells recognize viral particles on epithelial cells due to the hyperactivation of CD8 + T-cells. The hyperactivation of CD8 + T cells was similar to that observed in drug hypersensitivity reactions. Hence, the relationship between antiretroviral drugs and EM has been well established. This includes the administration of other drugs to HIV-infected individuals to manage opportunistic infections. Thus, multiple triggers may be present simultaneously in HIV-infected individuals. This article highlights the potential direct and indirect role that HIV infection may play in the development of EM and the clinical dilemma that arises in the management of HIV-infected patients with this condition. These patients may require additional medications to manage opportunistic infections, many of which can also trigger hypersensitivity reactions leading to EM.

Solubility, Thermodynamic Parameters, and Dissolution Properties of 17-α Hydroxyprogesterone in 13 Pure Solvents.

The static gravimetric method was used to measure the solubility of 17-α hydroxyprogesterone (OHP) in 13 pure solvents ranging from 278.15 to 323.15 K. The results indicate that the experimental solubility of OHP increases with increasing temperature. The experimental solubility data were correlated by the selected van't Hoff model, λh model, modified Apelblat model, Yaws model, and nonrandom two-liquid (NRTL) model. The fitting results show that the Yaws model can give better correlation results by fitting 13 different pure solvent systems. Based on the NRTL equation, the thermodynamic analysis of solubility data showed that the mixing process was spontaneous. The Hansen solubility parameters (HSPs) and solvent effect were applied to explore these solubility characteristics. Finally, the thermodynamic properties ΔsolH°, ΔsolS°, ΔsolG°, %ξH, and %ξTS were calculated by the van't Hoff model equation. The results showed that ΔsolH°, ΔsolS°, and ΔsolG° are all positive values, indicating that the dissolution of OHP in the selected solvent is an endothermic reaction with increasing entropy.

Pharmacokinetics of single dose doxycycline in the rectum, vagina, and urethra: implications for prevention of bacterial sexually transmitted infections.

BACKGROUND: Clinical trials showed a single oral dose of doxycycline taken after sex protects against STIs among men who have sex with men (MSM) but not women. Pharmacokinetic data at vaginal, rectal and penile sites of STI exposure are lacking. We examined vaginal, rectal and urethral doxycycline concentrations in men and women to better inform STI prevention. METHODS: Doxycycline pharmacokinetics in male and female participants 18-59 years of age were evaluated in blood and urine and on rectal and vaginal swabs collected at 1, 2, 4, 8, 24, 48, 72, 96 and 168 h after receiving a 200 mg oral doxycycline dose in a non-randomised single dose open label single centre study in Atlanta, Georgia. Rectal, vaginal, and cervical biopsies and male urethral swabs were collected 24 h after dosing (Trial registration: NCT04860505). Doxycycline was measured by liquid chromatography-mass spectrometry. FINDINGS: Eleven male and nine female participants participated in the study. Doxycycline concentrations on rectal and vaginal swabs collected up to 96 h after dosing were approximately twice those of plasma and remained above minimum inhibitory concentrations (MICs) for at least four, three, and two days for Chlamydia trachomatis, Treponema pallidum, and tetracycline-sensitive Neisseria gonorrhoeae, respectively. Geometric mean doxycycline concentrations in male urethral secretions (1.166 µg/mL; 95% CI 0.568-2.394 µg/mL), male rectal (0.596 µg/g; 0.442-0.803 µg/g), vaginal (0.261 µg/g; 0.098-0.696 µg/g) and cervical tissue (0.410 µg/g; 0.193-0.870 µg/g) in biopsies collected 24 h after dosing exceeded MICs. Plasma and urine doxycycline levels defined adherence markers up to four and seven days postdosing, respectively. No adverse events were reported in this study. INTERPRETATION: Doxycycline efficiently distributes to the rectum, vagina and urethra. Findings can help explain efficacy of STI prevention by doxycycline. FUNDING: Funded by CDC intramural funds, CDC contract HCVJCG-2020-45044 (to CFK).

Comparing Antoine parameter sources for accurate vapor pressure prediction across a range of temperatures.

Determining the vapor pressure of a substance at the relevant process temperature is a key component in conducting an exposure assessment to ascertain worker exposure. However, vapor pressure data at various temperatures relevant to the work environment is not readily available for many chemicals. The Antoine equation is a mathematical expression that relates temperature and vapor pressure. The objective of this analysis was to compare Antoine parameter data from 3 independent data sources; Hansen, Yaws, and Custom data and identify the source that generates the most accurate vapor pressure values with the least bias, relative to the referent data set from the CRC Handbook of Chemistry and Physics. Temperatures predicted from 3 different Antoine sources across a range of vapor pressures for 59 chemicals are compared to the reference source. The results show that temperatures predicted using Antoine parameters from the 3 sources are not statistically significantly different, indicating that all 3 sources could be useful. However, the Yaws dataset will be used in the SDM 2.0 because the data is readily available and robust.

Dynamic of land use and vegetation change in the eastern bank of Bénoué (North Cameroon).

The eastern part of the Benoue River bank is undergoing degradation marked by a significant decrease in vegetation cover and woody resources due to anthropogenic activities and climatic. The main objective of this study is to analyze the farmers' knowledge of vegetation evolution and the dynamics of land use using satellite images in the east of the bank of the Benoue. The methodological approach used is an integrated one combining field surveys, remote sensing, mapping, and modeling. The results obtained show that 88% of the population surveyed believe that the area covered by vegetation has decreased. The reasons for this decrease are numerous, but the main one remains the strong anthropic activity that would be at the origin of the progressive degradation of the land. The evolutionary trend of plant formations is essentially regressive for natural formations from 1991 to 2021. The analysis of the evolution of land use showed that in the Rey-Bouba district during 1991, 58.24% of the area formerly made up of dense woody formations regressed considerably to 25.77% in 2021. The same is true for the Bibemi district where the area of wooded zone has decreased from 65.47% in 1991 to 28.45% of the total area in 2021. This regression of the surface area of wooded formations was done to the benefit of anthropized occupation classes whose area has increased. They suggest an effective awareness in the monitoring of the dynamics of the vegetation cover subjected to anthropic pressures and climatic variations for a better-integrated management of the vegetation of this area.

Prevalence of transfusion-transmitted infections in hospitalized patients before transfusion and volunteer blood donors in Zhejiang Province, China.

OBJECTIVES: To assess the need for screening of transfusion-transmitted infections (TTIs) in blood products, we assessed TTI seroprevalence in blood donors and hospitalized patients. METHODS: We collected 2760 serum samples from three regions of Hangzhou, Ningbo and Huzhou from April 2021 to March 2022, and they tested by enzyme-linked immunosorbent assay (ELISA) for Hepatitis B surface antigen (HBsAg), Hepatitis C (HCV), Treponema pallidum (TP), Cytomegalovirus (CMV), Epstein-Barr virus (EBV), Hepatitis E virus (HEV) and Human T-cell lymphotropic virus type 1/2 (HTLV-1/2) antibody levels. RESULTS: Screening test results showed that the positive rates for HBsAg, anti-HCV and anti-TP were 3.01 %, 0.39 % and 0.18 %, respectively. The positive rates for CMV IgM and CMV IgG were 0.76 % and 96.96 %, while the positive rates for EB VCA-IgM and EB EA-IgG were 1.88 % and 10.47 %; those for HEV IgM and HEV IgG were 1.16 % and 26.05 %, while the HTLV-1/2 antibody positive rate was 0.04 %. The positive rates for CMV IgG, EB EA-IgG and HEV IgG in hospitalized patients before transfusion were higher than in volunteer blood donors, and the difference was statistically significant (P < 0.05). The overall co-infection rate was 0.29 %. The positive rates for EB VCA-IgM in the males were significantly higher than in females, and EB VCA-IgM and HEV IgG prevalence varied significantly by age. CONCLUSION: Our data demonstrate the risk of TTI exposure and TTI transmission in the Zhejiang population, which poses a threat to blood safety. It is hoped that expansion of pathogen categories (CMV, EBV, HEV and HTLV-1/2) and blood screening programs will contribute to the future adoption of scientific blood transfusion methods.

Aetiological molecular identification of sexually transmitted infections that cause urethral discharge syndrome and genital ulcer disease in Brazilian men: a nationwide study.

BACKGROUND: Little is known about the aetiology of urethral discharge syndrome (UDS) and genital ulcer disease (GUD) in Brazil due to limited access to laboratory tests and treatment based mainly on the syndromic approach. OBJECTIVES: To update Brazilian treatment guidelines according to the current scenario, the first nationwide aetiological study for UDS and GUD was performed. METHODS: Male participants with urethral discharge (UD) and/or genital ulcer (GU) reports were enrolled. Sample collection was performed by 12 sentinel sites located in the five Brazilian regions. Between 2018 and 2020, 1141 UD and 208 GU samples were collected in a Universal Transport Medium-RT (Copan). A multiplex quantitative PCR kit (Seegene) was used to detect UD: Chlamydia trachomatis (CT), Mycoplasma genitalium (MG), M. hominis (MH), Neisseria gonorrhoeae (NG), Trichomonas vaginalis (TV), Ureaplasma parvum (UP), U. urealyticum (UU) and another kit to detect GU: cytomegalovirus (CMV), Haemophilus ducreyi (HD), herpes simplex virus type 1 (HSV1), herpes simplex virus type 2 (HSV2), lymphogranuloma venereum (LGV), Treponema pallidum (TP) and varicella-zoster virus (VZV). RESULTS: In UD samples, the frequency of pathogen detection was NG: 78.38%, CT: 25.6%, MG: 8.3%, UU: 10.4%, UP: 3.5%, MH: 3.5% and TV: 0.9%. Coinfection was assessed in 30.9% of samples, with 14.3% of NG/CT coinfection. The most frequent pathogen identified in GU was HSV2, present in 40.8% of the samples, followed by TP at 24.8%, LGV and CMV at 1%, and HSV1 at 0.4%. Coinfection of TP/HSV2 was detected in 4.4% of samples. VZV and HD were not detected. In 27.7% of the GU samples, no pathogen was detected. CONCLUSION: This study provided the acquisition of unprecedented data on the aetiology of UDS and GUD in Brazil, demonstrated the presence of a variety of pathogens in both sample types and reaffirmed the aetiologies known to be most prevalent globally.

MOB-mediated regulation of septation initiation network (SIN) signaling is required for echinocandin-induced hyperseptation in Aspergillus fumigatus.

Aspergillus fumigatus is a major invasive mold pathogen and the most frequent etiologic agent of invasive aspergillosis. The currently available treatments for invasive aspergillosis are limited in both number and efficacy. Our recent work has uncovered that the ß-glucan synthase inhibitors, the echinocandins, are fungicidal against strains of A. fumigatus with defects in septation initiation network (SIN) kinase activity. These drugs are known to be fungistatic against strains with normal septation. Surprisingly, SIN kinase mutant strains also failed to invade lung tissue and were significantly less virulent in immunosuppressed mouse models. Inhibiting septation in filamentous fungi is therefore an exciting therapeutic prospect to both reduce virulence and improve current antifungal therapy. However, the SIN remains understudied in pathogenic fungi. To address this knowledge gap, we characterized the putative regulatory components of the A. fumigatus SIN. These included the GTPase, SpgA, it's two-component GTPase-activating protein, ByrA/BubA, and the kinase activators, SepM and MobA. Deletion of spgA, byrA, or bubA resulted in no overt septation or echinocandin susceptibility phenotypes. In contrast, our data show that deletion of sepM or mobA largely phenocopies disruption of their SIN kinase binding partners, sepL and sidB, respectively. Reduced septum formation, echinocandin hypersusceptibility, and reduced virulence were generated by loss of either gene. These findings provide strong supporting evidence that septa are essential not only for withstanding the cell wall disrupting effects of echinocandins but are also critical for the establishment of invasive disease. Therefore, pharmacological SIN inhibition may be an exciting strategy for future antifungal drug development.IMPORTANCESepta are important structural determinants of echinocandin susceptibility and tissue invasive growth for the ubiquitous fungal pathogen Aspergillus fumigatus. Components of the septation machinery therefore represent promising novel antifungal targets to improve echinocandin activity and reduce virulence. However, little is known about septation regulation in A. fumigatus. Here, we characterize the predicted regulatory components of the A. fumigatus septation initiation network. We show that the kinase activators SepM and MobA are vital for proper septation and echinocandin resistance, with MobA playing an essential role. Null mutants of mobA displayed significantly reduced virulence in a mouse model, underscoring the importance of this pathway for A. fumigatus pathogenesis.

Vigilância sorológica integrada de doenças transmissíveis mediante ensaio multiplex com microesferas na Região das Américas: Relatório da quarta reunião regional

Este documento apresenta um resumo das questões discutidas na Quarta Reunião Regional sobre Vigilância Sorológica Integrada de Doenças Transmissíveis Mediante Ensaio Multiplex na Região das Américas. Essa iniciativa, iniciada em 2016, é uma parceria entre os países da Região, o Centro de Controle e Prevenção de Doenças (CDC) dos Estados Unidos e a Organização Pan-Americana da Saúde que visa utilizar a vigilância sorológica integrada como ferramenta complementar aos sistemas de vigilância epidemiológica. A vigilância sorológica complementa a vigilância epidemiológica convencional ao fornecer informações sobre a exposição a patógenos que não são identificados por meio de vigilância sistemática e que possam estar circulando ou ressurgindo nas populações. Sua implementação nos países da Região das Américas permitiu caracterizar os perfis de imunidade a doenças transmissíveis para as quais não se dispunha de informações de referência (ou cujas informações disponíveis não estavam atualizadas); é o caso de doenças como estrongiloidíase, teníase/cisticercose, bouba e tracoma, entre outras. No ensaio multiplex, é possível detectar até 50, 100 ou 500 antígenos simultaneamente, dependendo do instrumento utilizado, a partir de um volume de amostra muito pequeno (<1 µl). Esse sistema permite a criação de ensaios ajustados às necessidades de saúde pública de cada programa, com um custo incremental muito baixo para a inclusão de antígenos adicionais. Na quarta reunião, realizada em março de 2023, buscou-se analisar os avanços e as lições aprendidas com o uso da vigilância sorológica integrada de doenças transmissíveis usando a plataforma de ensaio multiplex na Região das Américas, bem como analisar e pactuar as ações necessárias para usar essa tecnologia a fim de melhorar as decisões programáticas de saúde pública.

Integrated Serological Surveillance of Communicable Diseases using the Multiplex Bead Assay in the Region of the Americas: Report of the Fourth Regional Meeting

This document presents a summary of the topics discussed at the Fourth Regional Meeting on Integrated Serological Surveillance of Communicable Diseases using the Multiple Bead Assay (MBA) in the Region of the Americas. This initiative, which began in 2016, is a partnership between countries in the Region, the United States Centers for Disease Control and Prevention (CDC) and the Pan American Health Organization for the use of integrated serosurveillance as a tool to complement epidemiological surveillance systems. Serovigilance complements conventional epidemiological surveillance by providing information on exposure to pathogens that are not identified through routine surveillance and that may be circulating or re-emerging in populations. Its implementation in the countries of the Region of the Americas has made it possible to characterize the immunity profiles of communicable diseases for which no reference information was available or where the available information was not updated (e.g., for diseases such as strongyloidiasis, taeniasis and cysticercosis, and yaws). MBA allows up to 50, 100 or 500 antigens to be detected simultaneously, depending on the instrument used, with a very small sample volume (<1 µL). This system allows the creation of assays tailored to the public health needs of each program, with a very low incremental cost for adding antigens. The fourth meeting, held in March 2023, discussed progress and lessons learned in the use of integrated serosurveillance of communicable diseases using the multiple bead assay platform in the Region of the Americas. The meeting also reviewed and agreed on actions to employ MBA to improve programmatic public health decisions.

STI prevalence, partner notification and HIV risk perception in a cohort of women completing STI screening as part of a safer conception study.

BACKGROUND: Integrating STI and pre-exposure prophylaxis (PrEP) care may optimize sexual and reproductive health. METHODS: We nested an STI-sub-study within an HIV prevention cohort (Parent study) of 18-35-year-old women from South Africa, planning pregnancy with a partner with HIV or of unknown-serostatus. Parent-study women completed annual surveys regarding HIV-risk perceptions and were offered oral PrEP. PrEP initiators completed quarterly plasma tenofovir testing. Sub-study women completed STI screening at enrollment, 6 months, onset of pregnancy, and in the third trimester via examination, vaginal swabs tested via PCR for Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, Mycoplasma genitalium, and blood tested for Treponema pallidum. Follow-up was six months. Women with STIs were treated, offered partner notification (PN) cards, and surveyed regarding PN practices. We describe STI prevalence and incidence, and model factors associated with prevalent infection. STI sub-study and Parent-study-only participants were matched on age and number of days on study to assess HIV-risk perception scores between the two groups and the proportion with detectable tenofovir. RESULTS: Among 50 sub-study participants, 15 (30%) had prevalent STI. All 13 completing follow-up reported PN. Most did not prefer assisted PN. Mean HIV risk perception scores and proportion with detected plasma TFV were similar across groups. CONCLUSIONS: High STI prevalence supports the importance of laboratory screening to optimize sexual health for women planning pregnancy. Rates of self-reported PN are reassuring; low interest in assisted PN suggests the need for alternative approaches. Enhanced STI care did not affect HIV-risk perception or PrEP adherence, however both were relatively high in this cohort.

Prior visual experience increases children's use of effective haptic exploration strategies in audio-tactile sound-shape correspondences.

Sound-shape correspondence refers to the preferential mapping of information across the senses, such as associating a nonsense word like bouba with rounded abstract shapes and kiki with spiky abstract shapes. Here we focused on audio-tactile (AT) sound-shape correspondences between nonsense words and abstract shapes that are felt but not seen. Despite previous research indicating a role for visual experience in establishing AT associations, it remains unclear how visual experience facilitates AT correspondences. Here we investigated one hypothesis: seeing the abstract shapes improve haptic exploration by (a) increasing effective haptic strategies and/or (b) decreasing ineffective haptic strategies. We analyzed five haptic strategies in video-recordings of 6- to 8-year-old children obtained in a previous study. We found the dominant strategy used to explore shapes differed based on visual experience. Effective strategies, which provide information about shape, were dominant in participants with prior visual experience, whereas ineffective strategies, which do not provide information about shape, were dominant in participants without prior visual experience. With prior visual experience, poking-an effective and efficient strategy-was dominant, whereas without prior visual experience, uncategorizable and ineffective strategies were dominant. These findings suggest that prior visual experience of abstract shapes in 6- to 8-year-olds can increase the effectiveness and efficiency of haptic exploration, potentially explaining why prior visual experience can increase the strength of AT sound-shape correspondences.

Establishment of reference measurement procedure and reference material for Treponema pallidum.

Stem cell preparations, as a new type of biotherapeutic product, should be subject to strict quality control in terms of cell safety. The testing of stem cell donors and blood products used in stem cell cultures, including but not limited to Treponema pallidum, is needed to reduce the risk of transmission of infectious diseases by stem cell medical products. In this study, a reference measurement procedure (RMP) was established based on digital PCR (dPCR). A homogeneous reference material (RM) of TP containing the tpp47 gene has been developed and characterized. Two dPCR assays (A and B) show ideal linearity within five orders of magnitude. The limit of quantification (LoQ) for both assays is 57 copies/reaction; the limits of detection (LoD) are 9.69 and 9.59 copies/reaction, respectively. The quantitative results of the established duplex dPCR assay are in good agreement. The RM of TP containing the tpp47 gene has been developed and characterized. The reference value with its expanded uncertainty is (2.21 ± 0.22) × 106 copies per µL determined by the established dPCR RMP. The developed dPCR was validated by applying a simulated stem cell matrix, and no impact was observed on the accuracy of dPCR. By providing an accurate reference value for the absolute copy number of the target gene, the developed RM can be used to improve the reliability of TP testing in the production of stem cell preparations and clinical diagnostics.

The current status of neglected tropical diseases in Japan: A scoping review.

Little attention has been paid to neglected tropical diseases (NTDs) in high-income countries and no literature provides an overview of NTDs in Japan. This scoping review aims to synthesize the latest evidence and information to understand epidemiology of and public health response to NTDs in Japan. Using three academic databases, we retrieved articles that mentioned NTDs in Japan, written in English or Japanese, and published between 2010 and 2020. Websites of key public health institutions and medical societies were also explored. From these sources of information, we extracted data that were relevant to answering our research questions. Our findings revealed the transmission of alveolar echinococcosis, Buruli ulcer, Chagas disease, dengue, foodborne trematodiases, mycetoma, scabies, and soil-transmitted helminthiasis as well as occurrence of snakebites within Japan. Other NTDs, such as chikungunya, cystic echinococcosis, cysticercosis, leishmaniasis, leprosy, lymphatic filariasis, rabies, and schistosomiasis, have been imported into the country. Government agencies tend to organize surveillance and control programs only for the NTDs targeted by the Infectious Disease Control Law, namely, echinococcosis, rabies, dengue, and chikungunya. At least one laboratory offers diagnostic testing for each NTD except for dracunculiasis, human African trypanosomiasis, onchocerciasis, and yaws. No medicine is approved for treatment of Chagas disease and fascioliasis and only off-label use drugs are available for cysticercosis, opisthorchiasis, human African trypanosomiasis, onchocerciasis, schistosomiasis, and yaws. Based on these findings, we developed disease-specific recommendations. In addition, three policy issues are discussed, such as lack of legal frameworks to organize responses to some NTDs, overreliance on researchers to procure some NTD products, and unaffordability of unapproved NTD medicines. Japan should recognize the presence of NTDs within the country and need to address them as a national effort. The implications of our findings extend beyond Japan, emphasizing the need to study, recognize, and address NTDs even in high-income countries.

Low genetic diversity of Treponema pallidum ssp. pertenue (TPE) isolated from patients' ulcers in Namatanai District of Papua New Guinea: Local human population is infected by three TPE genotypes.

Yaws is an endemic disease caused by Treponema pallidum subsp. pertenue (TPE) that primarily affects children in rural regions of the tropics. The endemic character of yaws infections and the expected exclusive reservoir of TPE in humans opened a new opportunity to start a yaws eradication campaign. We have developed a multi-locus sequence typing (MLST) scheme for TPE isolates combining the previously published (TP0548, TP0488) and new (TP0858) chromosomal loci, and we compared this typing scheme to the two previously published MLST schemes. We applied this scheme to TPE-containing clinical isolates obtained during a mass drug administration study performed in the Namatanai District of Papua New Guinea between June 2018 and December 2019. Of 1081 samples collected, 302 (28.5%) tested positive for TPE DNA, from which 255 (84.4%) were fully typed. The TPE PCR-positivity in swab samples was higher in younger patients, patients with single ulcers, first ulcer episodes, and with ulcer duration less than six months. Non-treponemal serological test positivity correlated better with PCR positivity compared to treponema-specific serological tests. The MLST revealed a low level of genetic diversity among infecting TPE isolates, represented by just three distinct genotypes (JE11, SE22, and TE13). Two previously used typing schemes revealed similar typing resolutions. Two new alleles (one in TP0858 and one in TP0136) were shown to arise by intragenomic recombination/deletion events. Compared to samples genotyped as JE11, the minor genotypes (TE13 and SE22) were more frequently detected in samples from patients with two or more ulcers and patients with higher values of specific TP serological tests. Moreover, the A2058G mutation in the 23S rRNA genes of three JE11 isolates was found, resulting in azithromycin resistance.

The association between non-viral sexually transmitted infections and pregnancy outcome in Latin America and the Caribbean: A systematic review.

Introduction: Non-viral sexually transmitted infections are known to be associated with adverse pregnancy outcomes. For these pathogens, standard antenatal screening is not broadly performed in Latin America and the Caribbean. The aim of this study was to comprehensively review the association of non-viral sexually transmitted infections and neonatal outcomes among pregnant women in the region. Methods: Four databases (PubMed, Embase, SciELO and LILACS) were examined to identify eligible studies published up to September 2022. English or Spanish cross-sectional, case-control and cohort studies assessing the association of non-viral sexually transmitted infections and adverse pregnancy outcomes were evaluated. Articles were firstly screened by means of title and abstract. Potential articles were fully read and assessed for inclusion according to the eligibility criteria. Snowballing search was performed by screening of bibliographies of the chosen potentially relevant papers. Risk of bias within studies was assessed using the Joanna Briggs Institute reviewer's manual. Results: A selection of 10 out of 9772 search records from five Latin America and the Caribbean countries were included. Six studies associated Treponema pallidum infection with preterm birth (1/6), history of previous spontaneous abortion (2/6), fetal and infant death (1/6), low birth weight (1/6) and funisitis of the umbilical cord (1/6). Three studies associated Chlamydia trachomatis infection with preterm birth (2/3), ectopic pregnancy (1/3) and respiratory symptoms on the newborn (1/3). One study associated Mycoplasma genitalium infection with preterm birth. Conclusion: This review provides evidence on the association of non-viral sexually transmitted infections with adverse pregnancy outcomes. Further investigation is needed to establish more associations between non-viral sexually transmitted infections and pregnancy outcome, especially for Mycoplasma genitalium, Trichomonas vaginalis and Neisseria gonorrhoeae. Overall, this review calls for more research for public health interventions to promote screening of non-viral sexually transmitted infections during pregnancy, among high-risk population groups of pregnant women living in the region.

Treponema pallidum protein Tp47 induced prostaglandin E2 to inhibit the phagocytosis in human macrophages.

BACKGROUND: During Treponema pallidum (T. pallidum) infection, the host's immune system actively engages in pursuit and elimination of T. pallidum, while T. pallidum skillfully employs various mechanisms to evade immune recognition. Macrophages exhibit incomplete clearance of T. pallidum in vitro and the underlying mechanism of how T. pallidum resists the attack of macrophage remains unclear. OBJECTIVES: To investigate the effect of T. pallidum membrane protein Tp47 on the phagocytosis of macrophages. METHODS: THP-1-derived macrophages were used to investigate the role of Tp47 in the secretion of Prostaglandin E2 (PGE2) in macrophages and the mechanism by which Tp47 induced the production of PGE2, as well as the impact of PGE2 on the macrophage's phagocytosis. RESULTS: Tp47 (1-10 µg/mL) significantly inhibited the phagocytosis of latex beads and T. pallidum in macrophages (p ≤ 0.05). PGE2 production by macrophages could be induced by Tp47, and the phagocytic function of macrophages could be restored using PGE2 antibody. Tp47 produced PGE2 by activating the PERK/NF-κB/COX-2 pathway in macrophages. Inhibitors targeting PERK, NF-κB and COX-2, respectively, reduced the level of PGE2 and restored the phagocytic function of macrophages. CONCLUSION: Tp47-induced PGE2 production via the PERK/NF-κB/COX-2 pathway contributed to macrophage phagocytosis inhibition, which potentially contributes to immune evasion during the T. pallidum infection.

Modelling of doxycycline-based prevention of bacterial sexually transmitted infections in comparison to condom-based and test-based prevention.

Background: Doxycycline-based prevention of bacterial sexually transmitted infections (STIs) has been assessed in various studies and has been recommended by the European AIDS Clinical Society to be proposed to persons with repeated STIs on a case-by-case basis. However, while good preventive effects could be shown for Chlamydia trachomatis and Treponema pallidum in Europe, no reliable prevention against doxycycline resistance-affected bacterial causes of STIs like Neisseria gonorrhoeae and Mycoplasma genitalium was confirmed. Methods: In a modelling-approach, we assessed potential beneficial effects even against the latter microorganisms in case of optimized adherence with doxycycline prevention. These effects were modelled for Germany in comparison to traditional prevention schemes like condom-based STI-prevention and testing-as-prevention. Results: With estimated risk reduction in the ranges of 86% for N. gonorrhoeae and of 82% for Mycoplasma genitalium, expectable preventive efficacy similar to alternative preventive approaches could be calculated in case of optimized adherence with doxycycline prevention. In case of repeated risk exposure, the preventive potential of condom-based prevention was decreased compared to both optimized doxycycline prevention and testing-as-prevention. Conclusions: As suggested by the applied modelling, the preventive effect of optimized doxycycline prevention against bacterial STIs is in a similar range, like other common prevention strategies.