Modeling the HIV epidemic in MSM in Cyprus: reaching only the 95-95-95 cascade of care targets fails to reduce HIV incidence by 90% in 2030.

National responses should be improved and accelerated to meet the target of ending the Acquired ImmunoDeficiency Syndrome (AIDS) epidemic by 2030. In the Republic of Cyprus, Men who have Sex with Men (MSM) are disproportionately affected by Human Immunodeficiency Virus (HIV), accounting approximately for half of all annual HIV diagnoses. This study assesses the evolution of HIV incidence in MSM in Cyprus until 2030 using a model calibrated to Cypriot epidemiological data. Four scenarios were examined: status quo, two scenarios focusing on introducing Pre-Exposure Prophylaxis (PrEP), and a 90% HIV incidence reduction scenario. Reaching only the 95-95-95 HIV cascade of care targets among MSM would reduce HIV incidence by 48.6% by 2030 compared to 2015. Initiating a PrEP intervention only for high risk MSM would cause a modest further reduction in HIV incidence. To meet the 90% reduction target, PrEP should be expanded to both high and medium risk MSM and, after 2025, behavioral interventions should be implemented so as high-risk MSM gradually move to the medium-risk category. Cyprus will not reach the HIV incidence reduction target by 2030 unless PrEP is gradually promoted and delivered to all high and medium risk MSM along with awareness and behavioral interventions.

Sharp increase in gonorrhoea notifications among young people, EU/EEA, July 2022 to June 2023.

Gonorrhoea cases increased steeply in women aged 20 to 24 years across 15 EU/EEA countries in July to December 2022 and January to June 2023 with, respectively, 73% and 89% more cases reported than expected, based on historical data from 2015 to 2019. Smaller increases among men due to heterosexual transmission were observed in nine EU/EEA countries. Interventions to raise awareness among young people about sexually transmitted infection risks are needed, emphasising the benefit of safe sexual practices and testing.

Gut and airway microbiota and their role in COVID-19 infection and pathogenesis: a scoping review.

BACKGROUND: The SARS-CoV-2 virus is responsible for the COVID-19 pandemic. Researchers have been studying the pathogenesis of the virus with the aim to improve our current diagnosis and management strategies. The microbiota have been proposed to play a key role in the pathogenesis of the disease. PURPOSE: To investigate and report on the current available evidence on any associations between the gut and/or airway microbiota and the pathogenesis of COVID-19. METHODS: Using a predefined protocol in compliance with the PRISMA guidelines, a search was conducted on MEDLINE, Science Direct, DOAJ and Cochrane databases on primary research studies assessing the association between COVID-19 infection and the gut and/or airway microbiota. RESULTS: Twenty-two studies were included in the current review; nineteen studies concluded an association between the gut and/or airway dysbiosis and SARS-CoV-2, while 3 studies failed to observe a significant association between the airway microbiome and SARS-CoV-2 infection. Specifically, most studies reported a decrease in microbial diversity and therefore development of intestinal dysbiosis in COVID-19-positive patients compared to healthy controls as well as a possible association between increased intestinal dysbiosis and disease severity. CONCLUSION: During infection with SARS-CoV-2, there are significant changes in the composition of the gut and airway microbiota. Furthermore, the gut microbiota may have a more important role than the airway microbiota in COVID-19 infection. In the future, studies should be more carefully designed to derive more conclusive evidence on the role of the gut and airway microbiota following infection with SARS-CoV-2 which will lead to the formulation of better management strategies in combating COVID-19.

Comprehensive Genetic Characterization of Four Novel HIV-1 Circulating Recombinant Forms (CRF129_56G, CRF130_A1B, CRF131_A1B, and CRF138_cpx): Insights from Molecular Epidemiology in Cyprus.

Molecular investigations of the HIV-1 pol region (2253-5250 in the HXB2 genome) were conducted on sequences obtained from 331 individuals infected with HIV-1 in Cyprus between 2017 and 2021. This study unveiled four distinct HIV-1 putative transmission clusters, encompassing 19 previously unidentified HIV-1 recombinants. These recombinants, each comprising eight, three, four, and four sequences, respectively, did not align with previously established Circulating Recombinant Forms (CRFs). To characterize these novel HIV-1 recombinants, near-full-length genome sequences were successfully obtained for 16 of the 19 recombinants (790-8795 in the HXB2 genome) using an in-house-developed RT-PCR assay. Phylogenetic analyses, employing MEGAX and Cluster-Picker, along with confirmatory neighbor-joining tree analyses of subregions, were conducted to identify distinct clusters and determine subtypes. The uniqueness of the HIV-1 recombinants was evident in their exclusive clustering within generated maximum likelihood trees. Recombination analyses highlighted the distinct chimeric nature of these recombinants, with consistent mosaic patterns observed across all sequences within each of the four putative transmission clusters. Conclusive genetic characterization identified four novel HIV-1 CRFs: CRF129_56G, CRF130_A1B, CRF131_A1B, and CRF138_cpx. CRF129_56G exhibited two recombination breakpoints and three fragments of subtypes CRF56_cpx and G. Both CRF130_A1B and CRF131_A1B featured seven recombination breakpoints and eight fragments of subtypes A1 and B. CRF138_cpx displayed five recombination breakpoints and six fragments of subtypes CRF22_01A1 and F2, along with an unclassified fragment. Additional BLAST analyses identified a Unique Recombinant Form (URF) of CRF138_cpx with three additional recombination sites, involving subtype F2, a fragment of unknown subtype origin, and CRF138_cpx. Post-identification, all putative transmission clusters remained active, with CRF130_A1B, CRF131_A1B, and CRF138_cpx clusters exhibiting further growth. Furthermore, international connections were identified through BLAST analyses, linking one sequence from the USA to the CRF130_A1B strain, and three sequences from Belgium and Cameroon to the CRF138_cpx strain. This study contributes valuable insights into the dynamic landscape of HIV-1 diversity and transmission patterns, emphasizing the need for ongoing molecular surveillance and global collaboration in tracking emerging viral variants.

SARS CoV-2-Induced Viral Sepsis: The Role of Gut Barrier Dysfunction.

A considerable proportion of patients with severe COVID-19 meet Sepsis-3 criteria and share common pathophysiological mechanisms of multiorgan injury with bacterial sepsis, in absence of secondary bacterial infections, a process characterized as "viral sepsis". The intestinal barrier exerts a central role in the pathophysiological sequence of events that lead from SARS-CoV-2 infection to severe systemic complications. Accumulating evidence suggests that SARS-CoV-2 disrupts the integrity of the biological, mechanical and immunological gut barrier. Specifically, microbiota diversity and beneficial bacteria population are reduced, concurrently with overgrowth of pathogenic bacteria (dysbiosis). Enterocytes' tight junctions (TJs) are disrupted, and the apoptotic death of intestinal epithelial cells is increased leading to increased gut permeability. In addition, mucosal CD4(+) and CD8(+) T cells, Th17 cells, neutrophils, dendritic cells and macrophages are activated, and T-regulatory cells are decreased, thus promoting an overactivated immune response, which further injures the intestinal epithelium. This dysfunctional gut barrier in SARS-CoV-2 infection permits the escape of luminal bacteria, fungi and endotoxin to normally sterile extraintestinal sites and the systemic circulation. Pre-existing gut barrier dysfunction and endotoxemia in patients with comorbidities including cardiovascular disease, obesity, diabetes and immunosuppression predisposes to aggravated endotoxemia. Bacterial and endotoxin translocation promote the systemic inflammation and immune activation, which characterize the SARS-CoV-2 induced "viral sepsis" syndrome associated with multisystemic complications of severe COVID-19.

A Seven-Year Microbiological and Molecular Study of Bacteremias Due to Carbapenemase-Producing Klebsiella Pneumoniae: An Interrupted Time-Series Analysis of Changes in the Carbapenemase Gene's Distribution after Introduction of Ceftazidime/Avibactam.

Background: Ceftazidime/avibactam (CZA) is a new option for the treatment of KPC-producing Klebsiella pneumoniae. The aim of this study was to determine resistance patterns and carbapenemase genes among K. pneumoniae (CP-Kp) bacteremic isolates before and after CZA introduction. Methods: K. pneumoniae from blood cultures of patients being treated in a Greek university hospital during 2015−21 were included. PCR for blaKPC, blaVIM, blaNDM and blaOXA-48 genes was performed. Results: Among 912 K. pneumoniae bacteremias: 725 (79.5%) were due to carbapenemase-producing isolates; 488 (67.3%) carried blaKPC; 108 (14.9%) blaVIM; 100 (13.8%) blaNDM; and 29 (4%) carried a combination of blaKPC, blaVIM or blaNDM. The incidence of CP-Kp bacteremias was 59 per 100,000 patient-days. The incidence of CP-Kp changed from a downward pre-CZA trend to an upward trend in the CZA period (p = 0.007). BSIs due to KPC-producing isolates showed a continuous downward trend in the pre-CZA and CZA periods (p = 0.067), while BSIs due to isolates carrying blaVIM or blaNDM changed from a downward trend in the pre-CZA to an upward trend in the CZA period (p < 0.001). Conclusions: An abrupt change in the epidemiology of CP-Kp was observed in 2018, due to the re-emergence of VIM-producing isolates after the suppression of KPC-producing ones via the use of CZA.

Extensive Testing and Public Health Interventions for the Control of COVID-19 in the Republic of Cyprus between March and May 2020.

Coronavirus disease 2019 (COVID-19) has significantly affected the well-being of individuals worldwide. We herein describe the epidemiology of COVID-19 in the Republic of Cyprus during the first epidemic wave (9 March-3 May 2020). We analyzed surveillance data from laboratory-confirmed cases, including targeted testing and population screening. Statistical analyses included logistic regression. During the surveillance period, 64,136 tests (7322.3 per 100,000) were performed, 873 COVID-19 cases were diagnosed, and 20 deaths were reported (2.3%). Health-care workers (HCWs) represented 21.4% of cases. Overall, 19.1% of cases received hospital care and 3.7% required admission to Intensive Care Units. Male sex (adjusted Odds Ratio (aOR): 3.04; 95% Confidence Interval (CI): 1.97-4.69), increasing age (aOR: 1.56; 95%CI: 1.36-1.79), symptoms at diagnosis (aOR: 6.05; 95%CI: 3.18-11.50), and underlying health conditions (aOR: 2.08; 95%CI: 1.31-3.31) were associated with hospitalization. For recovered cases, the median time from first to last second negative test was 21 days. Overall, 119 primary cases reported 616 close contacts, yielding a pooled secondary attack rate of 12% (95%CI: 9.6-14.8%). Three population-based screening projects, and two projects targeting employees and HCWs, involving 25,496 people, revealed 60 positive individuals (0.2%). Early implementation of interventions with targeted and expanded testing facilitated prompt outbreak control on the island.

Inhaled Antimicrobials for Ventilator-Associated Pneumonia: Practical Aspects.

Positive experience with inhaled antibiotics in pulmonary infections of patients with cystic fibrosis has paved the way for their utilization in mechanically ventilated, critically ill patients with lower respiratory tract infections. A successful antibiotic delivery depends upon the size of the generated particle and the elimination of drug impaction in the large airways and the ventilator circuit. Generated droplet size is mainly affected by the type of the nebulizer employed. Currently, jet, ultrasonic, and vibrating mesh nebulizers are marketed; the latter can deliver optimal antibiotic particle size. Promising novel drug-device combinations are able to release drug concentrations of 25- to 300-fold the minimum inhibitory concentration of the targeted pathogens into the pulmonary alveoli. The most important practical steps of nebulization include pre-assessment and preparation of the patient (suctioning, sedation, possible bronchodilation, adjustment of necessary ventilator settings); adherence to the procedure (drug preparation, avoidance of unnecessary tubing connections, interruption of heated humidification, removal of heat-moisture exchanger); inspection of the procedure (check for residual in drug chamber, change of expiratory filter, return sedation, and ventilator settings to previous status); and surveillance of the patient for adverse events (close monitoring of the patient and particularly of peak airway pressure and bronchoconstriction). Practical aspects of nebulization are very important to ensure optimal drug delivery and safe procedure for the patient. Therefore, the development of an operational checklist is a priority for every department adopting this modality.

Epstein barr virus hemophagocytic lymphohistiocytosis related to rituximab use and immunopathogenetic insights.

Anti-CD20-based chemo-immunotherapeutic regimens have been suggested to assist in the management of Epstein-Barr virus (EBV)-induced hemophagocytic lymphohistiocytosis (HLH) and EBV-associated post-transplant lymphoproliferative disorders (EBV-PTLD), by reducing EBV viral load and EBV-induced inflammation. Herein we report a fatal EBV-related HLH in the context of Hodgkin lymphoma (HL)-like Richter's transformation of B chronic lymphocytic leukemia (B-CLL), two months after rituximab treatment. The complex balance between EBV driven T-cell stimulation and immunosuppressive therapy in the context of multiple immune deficits is discussed.