Patterns of Chlamydia trachomatis and Neisseria gonorrhoeae in different anatomical sites among Pre-Exposure Prophylaxis (PrEP) users in Brazil.

BACKGROUND: The presence of untreated sexually transmitted infections (STIs) significantly increases the chance of acquiring HIV. In Brazil, testing for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) among Pre-Exposure Prophylaxis (PrEP) users is insufficient, and syndromic treatment is a priority in clinical practice. Multi-site testing for CT/NG improves thescreening of asymptomatic cases and ensures timely treatment. Therefore, it is essential for HIV prevention. This study aims to test the importance of two-site testing for better screening of these pathogens and to determine whether the presence of symptoms is an indicator of CT/NG infection. METHODS: This is a cross-sectional study carried out in four public infectious diseases clinics in São Paulo State, Brazil between January of 2022 and March of 2023. All participants had an anal swab and a first-pass or mid-stream urine collected for CT/NG analysis by Polymerase chain reaction (PCR). Data about sociodemographic, sexual behavioural and clinical aspects were collected. Pathway analysis was used to examine the direct and indirect relationships between variables according to the theoretical model. RESULTS: We screened 171 PrEP users which had two samples collected, resulting in 342 samples. Comparing the anatomic sites, the urine samples showed lower sensitivity for CT and NG than anal samples. Gonorrhoea was directly linked to lower age (ß= -0.161, p = 0.001). Time of PrEP use was directly associated with CT infection (ß = 0.202; p = 0.042) and inversely associated with dysuria (ß= -0.121, p = 0.009). Lower occurrence of yellow-green secretion was linked to detection of CT (ß= -0.089, p = 0.005) and NG (ß= -0.048, p = 0.002) infections. Foul-smelling discharge was directly associated with CT (ß = 0.275, p = 0.004) and NG (ß = 0.295, p = 0.037) infection. CONCLUSION: The symptoms are a bad indicator of CT and NG infection, and the screening must be done in more than one site since most of the positive results would be missed if only urines were tested. In the case of testing only one anatomical site, specifically the urethra, the CT/NG incidence and prevalence would be underestimated. The two-sites testing improves detection rates of CT/NG, and PrEP follow-up benefits people offering STI testing.

Gasdermin-D activation by SARS-CoV-2 triggers NET and mediate COVID-19 immunopathology.

BACKGROUND: The release of neutrophil extracellular traps (NETs) is associated with inflammation, coagulopathy, and organ damage found in severe cases of COVID-19. However, the molecular mechanisms underlying the release of NETs in COVID-19 remain unclear. OBJECTIVES: We aim to investigate the role of the Gasdermin-D (GSDMD) pathway on NETs release and the development of organ damage during COVID-19. METHODS: We performed a single-cell transcriptome analysis in public data of bronchoalveolar lavage. Then, we enrolled 63 hospitalized patients with moderate and severe COVID-19. We analyze in blood and lung tissue samples the expression of GSDMD, presence of NETs, and signaling pathways upstreaming. Furthermore, we analyzed the treatment with disulfiram in a mouse model of SARS-CoV-2 infection. RESULTS: We found that the SARS-CoV-2 virus directly activates the pore-forming protein GSDMD that triggers NET production and organ damage in COVID-19. Single-cell transcriptome analysis revealed that the expression of GSDMD and inflammasome-related genes were increased in COVID-19 patients. High expression of active GSDMD associated with NETs structures was found in the lung tissue of COVID-19 patients. Furthermore, we showed that activation of GSDMD in neutrophils requires active caspase1/4 and live SARS-CoV-2, which infects neutrophils. In a mouse model of SARS-CoV-2 infection, the treatment with disulfiram inhibited NETs release and reduced organ damage. CONCLUSION: These results demonstrated that GSDMD-dependent NETosis plays a critical role in COVID-19 immunopathology and suggests GSDMD as a novel potential target for improving the COVID-19 therapeutic strategy.

HLA-G liver expression and HLA-G extended haplotypes are associated with chronic hepatitis C in HIV-negative and HIV-coinfected patients.

Chronic hepatitis C virus (HCV) infection induces liver damage and the HCV/Human Immunodeficiency Virus (HIV)-coinfection may further contribute to its progression. The HLA-G molecule inhibits innate and adaptive immunity and may be deleterious for chronically virus-infected cells. Thus we studied 204 HCV-mono-infected patients, 142 HCV/HIV-coinfected patients, 104 HIV-mono-infected patients and 163 healthy subjects. HLA-G liver expression was similarly induced in HCV and HCV/HIV specimens, increasing with advanced fibrosis and necroinflammatory activity, and with increased levels of liver function-related enzymes. Plasma soluble HLA-G (sHLA-G) levels were higher in HCV/HIV patients compared to HCV, HIV and to healthy individuals. sHLA-G continued to be higher in coinfected patients even after stratification of samples according to degree of liver fibrosis and necroinflammatory activity when compared to mono-infected patients. Some HLA-G gene haplotypes differentiated patient groups and presented few associations with liver and plasma HLA-G expression. HLA-G thus may help to distinguish patient groups.

Correction: Clinical profile and mortality in patients with T. cruzi/HIV co-infection from the multicenter data base of the "Network for healthcare and study of Trypanosoma cruzi/HIV co-infection and other immunosuppression conditions".

[This corrects the article DOI: 10.1371/journal.pntd.0009809.].

Gingival tissue as a reservoir for human immunodeficiency virus type 1: Preliminary results of a cross-sectional observational study.

BACKGROUND: Despite combined antiretroviral therapy (cART), total cure of immunodeficiency virus type 1 (HIV-1) infection remains elusive. Chronic periodontitis (CP) is strongly associated with HIV-1 infection. This condition is characterized by an intense inflammatory infiltrate mainly constituted of immune cells which in turn may be a valuable source of HIV-1 reactivation. This study aimed to determine if gingival tissue could act as a reservoir for HIV-1. METHODS: Twelve patients with HIV-1 and CP and 12 controls (no HIV-1-infection and no CP) were evaluated in a cross-sectional study. RNA viral load and interleukin (IL) levels were determined in blood plasma and saliva. Histological sections of gingival tissue were stained with fluorescent antibodies against p24 antigen and different cellular biomarkers. RESULTS: In six of the 12 patients, HIV RNA load was detected, despite cART; in three of them, expression of viral RNA was also detected in saliva. The levels of IL-2, IL-6, and IL-12 were higher in blood and saliva of patients with HIVand CP than controls. HIV-1 p24 antigen was detected by immunostaining in gingival biopsies of 10 of the 12 patients but in no controls. Immune markers for T cells and antigen-presenting cells were also identified in most patients and some controls. CONCLUSION: These preliminary data showing the detection of HIV-1 p24 antigen in the gingival biopsies of a significant part of patients with HIV-1 and CP under cART together with the presence of immune cells, plead for the existence of a HIV-1 reservoir in the gingival tissue of this population.

Hand hygiene by the nursing team in home care: a cross-sectional study.

OBJECTIVE: to identify whether nursing professionals carry out hand hygiene, how they do it, and what resources are available for this practice during home visits. METHOD: cross-sectional study conducted in a public Home Care service. The World Health Organization instrument was used to observe the hand hygiene technique, the time of performance, and the product used. RESULTS: a total of 940 hand hygiene opportunities taking place in 231 home visits were observed. Overall adherence was 14.4%, with the practice of hand hygiene being higher after contact with the patient (53.7%). Before aseptic procedures, after risk/exposure to body fluids, after contact with the patient's environment, and before contact with the patient, adherence was 0.4%. Regarding the quality of the technique, in none of the 135 practices the recommended steps were followed. As for the structure available in the households, 35 (15.2%) had accessible sinks and none had liquid soap and alcohol-based formulation. CONCLUSION: adherence to hand hygiene by nursing professionals in home care was low, the technique was not performed, and households did not have resources for the practice.

Clinical profile and mortality in patients with T. cruzi/HIV co-infection from the multicenter data base of the "Network for healthcare and study of Trypanosoma cruzi/HIV co-infection and other immunosuppression conditions".

OBJECTIVE: Chagas disease (CD) globalization facilitated the co-infection with Human Immunodeficiency Virus (HIV) in endemic and non-endemic areas. Considering the underestimation of Trypanosoma cruzi (T. cruzi)-HIV co-infection and the risk of life-threatening Chagas Disease Reactivation (CDR), this study aimed to analyze the major co-infection clinical characteristics and its mortality rates. METHODS: This is a cross-sectional retrospective multicenter study of patients with CD confirmed by two serological or one parasitological tests, and HIV infection confirmed by immunoblot. CDR was diagnosed by direct microscopy with detection of trypomastigote forms in the blood or other biological fluids and/or amastigote forms in inflammatory lesions. RESULTS: Out of 241 patients with co-infection, 86.7% were from Brazil, 47.5% had <200 CD4+ T cells/µL and median viral load was 17,000 copies/µL. Sixty CDR cases were observed. Death was more frequent in patients with reactivation and was mainly caused by CDR. Other causes of death unrelated to CDR were the manifestation of opportunistic infections in those with Acquired Immunodeficiency Syndrome. The time between the co-infection diagnosis to death was shorter in patients with CDR. Lower CD4+ cells count at co-infection diagnosis was independently associated with reactivation. Similarly, lower CD4+ cells numbers at co-infection diagnosis and male sex were associated with higher lethality in CDR. Additionally, CD4+ cells were lower in meningoencephalitis than in myocarditis and milder forms. CONCLUSION: This study showed major features on T. cruzi-HIV co-infection and highlighted the prognostic role of CD4+ cells for reactivation and mortality. Since lethality was high in meningoencephalitis and all untreated patients died shortly after the diagnosis, early diagnosis, immediate antiparasitic treatment, patient follow-up and epidemiological surveillance are essentials in T. cruzi/HIV co-infection and CDR managements.

Relationship between human immunodeficiency virus (HIV-1) infection and chronic periodontitis.

INTRODUCTION: Current studies show that, even in the era of antiretroviral therapies, HIV-1 infection is associated with more severe and frequent refractory chronic periodontitis. Areas covered: This review, based on a systematic analysis of the literature, intends to provide an update on factors that may be involved in the pathogenesis of periodontal disease in HIV-1-infected patients, including local immunosuppression, oral microbial factors, systemic inflammation, salivary markers, and the role of gingival tissue as a possible reservoir of HIV-1. Expert commentary: The therapeutic revolution of ART made HIV-1 infection a chronic controllable disease, reduced HIV-1 mortality rate, restored at least partially the immune response and dramatically increased life expectancy of HIV-1-infected patients. Despite all these positive aspects, chronic periodontitis assumes an important role in the HIV-1 infection status for activating systemic inflammation favoring viral replication and influencing HIV-1 status, and also acting as a possible reservoir of HIV-1. All these issues still need to be clarified and validated, but have important clinical implications that certainly will benefit the diagnosis and management of chronic periodontitis in HIV-1-infected patients, and also contributes to HIV-1 eradication.