Μελέτη διασποράς της επιδημίας HIV-1 στην Ελλάδα: εκτίμηση σημαντικών τοπικών δικτύων και χαρακτηρισμός τους

Εισαγωγή: Προηγούμενες μελέτες έχουν δείξει ότι οι Α1 και Β είναι οι επικρατέστεροι HIV-1 υπότυποι στην Ελλάδα, και παρουσιάζουν το μεγαλύτερο ποσοστό τοπικής διασποράς σε σχέση με άλλους υπότυπους και ανασυνδυασμένους τύπους του ιού. Σκοπός: Η διερεύνηση του τρόπου διασποράς των υπότυπων Α1 και Β στην Ελλάδα, η εύρεση όλων των τοπικών δικτύων μετάδοσης τους (επιμέρους επιδημίες), και η εκτίμηση των παραγόντων που σχετίζονται με την τοπική διασπορά του ιού, χρησιμοποιώντας μεθόδους μοριακής επιδημιολογίας. Υλικό: Μελετήθηκαν 1.230 αλληλουχίες υπότυπου Α1 και 2.156 υπότυπου Β με δειγματοληψία το διάστημα 1996-06/2015 στη Νότια Ελλάδα. Μέθοδοι: Τα φυλογενετικά δέντρα εκτιμήθηκαν με τη μέθοδο μέγιστης πιθανοφάνειας και ανάλυση bootstrap. Η ανάλυση επαναλήφθηκε 5 φορές για κάθε υπότυπο χρησιμοποιώντας κάθε φορά ένα τυχαία επιλεγμένο δείγμα αλληλουχιών αναφοράς με παγκόσμια δειγματοληψία μεγέθους 1.500 αλληλουχιών για τον Α1 και 2.000 για τον Β, αντίστοιχα. Η τοπική διασπορά του ιού (ποσοστό μονοφυλετικότητας) εκτιμήθηκε υπολογίζοντας το πηλίκο του αριθμού των αλληλουχιών σε φυλογενετικές ομάδες με δειγματοληψία >70% από Ελλάδα και του συνόλου των διαθέσιμων αλληλουχιών από Ελλάδα, ανά υπότυπο. Η στατιστική ανάλυση πραγματοποιήθηκε με τη μέθοδο της λογιστικής παλινδρόμησης. Αποτελέσματα: Για τον υπότυπο Α1 βρέθηκαν 23 τοπικά δίκτυα μετάδοσης με εύρος από 2 έως 1.059 αλληλουχίες, ενώ για τον Β βρέθηκαν 133 τοπικά δίκτυα με εύρος από 2 έως 157 αλληλουχίες. Τα ποσοστά μονοφυλετικότητας των Α1 και Β ήταν 91,46% (Ν=1.125) και 72,82% (Ν=1.570), αντίστοιχα. Tο 86,1% (Ν=1.059) των Α1 αλληλουχιών σχημάτισε μια μονοφυλετική ομάδα (τοπικό δίκτυο μετάδοσης). Οι HIV(+) με Α1 των οποίων οι αλληλουχίες εντοπίστηκαν εκτός δικτύων μετάδοσης (Ν=105) ήταν, κυρίως, ετεροφυλόφιλοι (Ν=54; 51,4%), μη-Ελληνικής εθνικότητας (Ν=45; 42,9%). H ανάλυση λογιστικής παλινδρόμησης έδειξε ότι η τοπική διασπορά του υπότυπου Α1 σχετίζεται με άνδρες (OR=1,8; p=0.034), MSM (OR=7,2; p<0.001), Ελληνικής εθνικότητας (OR=7,2; p<0.001), ενώ του Β με δειγματοληψία το διάστημα 2011-2015 (OR=7,21; p<0.001). Συμπεράσματα: H επιδημία του υπότυπου Α1 παρουσιάζει υψηλότερα επίπεδα τοπικής διασποράς σε σχέση με του Β. Οι HIV(+) με Α1 για τους οποίους δεν παρατηρήθηκε τοπική διασπορά είναι κυρίως ετεροφυλόφιλοι μη-Ελληνικής εθνικότητας, γεγονός που υποδεικνύει ότι αυτή η ομάδα πληθυσμού που έχει μολυνθεί με στελέχη Α1 με γεωγραφική προέλευση εκτός Ελλάδας, δεν σχετίζεται με περαιτέρω διασπορά και συνεπώς δημιουργία τοπικών επιδημιών.Introduction: Previous studies have shown that HIV-1 subtypes A1 and B are the predominant clades in Greece. Aim: To investigate the patters of subtypes A1 and B dispersal in Greece, to identify the proportion of infections occurred locally, and to estimate the factors that are associated with local transmissions, using molecular epidemiology methods. Material: We studied 1,230 A1 and 2,156 B sequences isolated from HIV-1 diagnosed patients during 1996-06/2015 in Greece. Sequences were available in the protease (PR) and partial reverse transcriptase (RT) regions. Methods: Maximum-likelihood (ML) phylogeny reconstruction with bootstrap evaluation was conducted in RAxML8, using GTR+G as nucleotide substitution model. Phylogenetic analysis was performed separately on the 1,230 A1 and 2,156 B sequences from Greece along with a random set of globally sampled sequences (A1: N=1,500; B: N=2,000), used as references. Phylogenetic analysis was performed for each subtype in five replicates, using a different reference dataset each time. Local transmission networks (LTNs) were defined as phylogenetic clusters including sequences from Greece at proportions >70% (geographic criterion), found in all five replicates (phylogenetic confidence). Local dispersal was estimated by dividing the number of sequences found within LTNs with the total number of sequences sampled in Greece for each subtype. The statistical analysis was carried out using multivariate logistic regression models. Presence in LTNs was the binary outcome variable, while age, period of sampling, risk group, nationality and gender were chosen as possible explanatory variables. Results: Phylogenetic analysis revealed that 91.5% (1,125 out of 1,230) of the A1 sequences sampled in Greece formed 23 LTNs. The size of the LTNs ranged between 2 and 1,059 sequences. The 86.1% of the A1 sequences fell within a single LTN consisted of 1,059 sequences. The rest of the A1 sequences (N=105, 8.5%) clustered at different points in the ML tree. The majority of the unclustered sequences had been isolated mainly from heterosexuals with non-Greek nationality. Phylogenetic analysis also revealed that 72.8% (1,570 out of 2,156) of the B sequences sampled in Greece formed 133 LTNs, with a range of 2 to 157 sequences. Multivariate logistic regression analysis showed that gender (male; OR=1.8; p=0.034), risk group (MSM; OR=7.2; p<0.001) and nationality (Greek; OR=7.2; p<0.001) were associated with regional clustering of subtype A1, while period of sampling (2011-2015; OR=7.21; p<0.001) with local transmissions of subtype B. 62 Conclusions: Our analysis suggests considerable differences in the levels of regional clustering of HIV-1 subtype A1 and B in Greece. For subtype A1 we found a lower number of introductions than for subtype B. This probably due to that subtype B is more frequently found in developed countries, suggesting that cross-border transmissions are more likely than non-B clades. It was also shown that the majority of A1 unclustered sequences had been isolated mainly from heterosexuals with non-Greek nationality. This finding suggests that this population group was infected with A1 strains with non-Greek origin and it is not related to further dispersal. Moreover, we found that local dispersal of subtype B transmissions is mostly associated with recent diagnosis

Real-world effectiveness of molnupiravir and nirmatrelvir/ritonavir as treatments for COVID-19 in patients at high risk

Background Using a retrospective cohort study design, we aimed to evaluate the effectiveness of molnupiravir and nirmatrelvir/ritonavir in patients with SARS-CoV-2 who were highly vulnerable. Methods The impact of each drug was determined via comparisons with age-matched control groups of patients positive for SARS-CoV-2 who did not receive oral antiviral therapy. Results Administration of molnupiravir significantly reduced the risk of hospitalization (odds ratio [OR], 0.40; P < .001) and death (OR, 0.31; P < .001) among these patients based on data adjusted for age, previous SARS-CoV-2 infection, vaccination status, and time elapsed since the most recent vaccination. The reductions in risk were most profound among elderly patients (≥75 years old) and among those with high levels of drug adherence. Administration of nirmatrelvir/ritonavir also resulted in significant reductions in the risk of hospitalization (OR, 0.31; P < .001) and death (OR, 0.28; P < .001). Similar to molnupiravir, the impact of nirmatrelvir/ritonavir was more substantial among elderly patients and in those with high levels of drug adherence. Conclusions Collectively, these real-world findings suggest that although the risks of hospitalization and death due to COVID-19 have been reduced, antivirals can provide additional benefits to members of highly vulnerable patient populations

Healthcare-associated infections and antimicrobial use in acute care hospitals in Greece, 2022; results of the third point prevalence survey

Abstract Background The burden of healthcare-associated infections (HAIs) and the extent of antimicrobial use (AU) are periodically recorded through Point Prevalence Surveys (PPS) in acute care hospitals coordinated by the European Centre for Disease Prevention and Control (ECDC). In previous PPSs, Greece demonstrated increased HAI and AU prevalence: 9% and 54.7% in 2011–2012, and 10% and 55.6% in 2016–2017, respectively. The 2022 PPS aimed to estimate HAIs and AU indicators among inpatients, especially amid the COVID-19 pandemic. Methods A cross-sectional study was conducted in 50 hospitals during October-December 2022, in Greece. Patients admitted before 8.00 a.m. of the survey day were observed. Patients with at least one HAI or receiving at least one antimicrobial agent were included. Data were collected by hospital infection control teams. Hospital and ward-level variables were analysed. Results From 9,707 inpatients, 1,175 had at least one HAI (12.1%), and 5,376 were receiving at least one antimicrobial (55.4%). Intensive care unit patients had the highest HAI (45.7%) and AU (71.3%) prevalence. Of the 1,408 recorded HAIs, lower respiratory tract (28.9%), bloodstream (20%), and urinary tract infections (13.1%) were the most common. Among 1,259 isolates, Klebsiella (20.5%) and Acinetobacter (12.8%) were most frequently identified. Resistance to first-level antibiotic markers was 69.3%. Among the 9,003 antimicrobials, piperacillin-tazobactam (10.9%), and meropenem (7.7%) were frequently prescribed. The ratio of broad-spectrum to narrow-spectrum antibiotics was 1.4. As defined by the 2021 WHO AWaRe (Access, Watch, Reserve) classification, restricted classes of Watch and Reserve agents comprised 76.7% of antibiotics. Usual indications were treatment of community-acquired infections (34.6%) and HAIs (22.9%). For surgical prophylaxis, cefoxitin was commonly used (20.2%), and typical courses (75.7%) lasted more than one day. HAI and AU prevalence were positively associated with bed occupancy (p = 0.027) and secondary hospitals (p = 0.014), respectively. Conclusions The 2022 PPS highlighted the increasing trend of HAI prevalence and high AU prevalence in Greece, the emergence of difficult-to-treat pathogens, and the extensive use of broad-spectrum antimicrobials. Strengthening infection control and antimicrobial stewardship programs in hospital settings is essential

Time Lag between COVID-19 Diagnosis and Symptoms Onset for Different Population Groups: Evidence That Self-Testing in Schools Was Associated with Timely Diagnosis among Children

Early identification of COVID-19 cases has been vital for reducing transmission and enabling treatment. In Greece, in autumn 2021 when Delta was the predominant circulating variant, unvaccinated citizens had to be tested before attending activities, and self-testing was required twice a week for students (5&ndash;17 years). Here, we describe the time of diagnosis by age group and possible exposure to assess testing strategies (September to November 2021). Information on the presence of symptoms at the time of diagnosis was available for 69,298 cases; 24,855 (36%) were asymptomatic or tested the same day as onset (early diagnosis), 21,310 (31%) reported testing one day after, and 23,133 (33%) did so two or more days after the onset of symptoms. The median lag was 2 days (1&ndash;14). Early diagnosis significantly differed among age groups (p-value &lt; 0.001) and was higher among children. For every one-year increase of age, the odds of an early diagnosis were reduced by 1%. Cases exposed during training activities or in settings such as accommodation centers and hospitals were more frequently diagnosed early. The percentage of persons having a positive self-test before a rapid test/PCR diagnosis ranged from 7% in the age group of 60 years and above to 86% in the age group of 5&ndash;17 years. The provision of self-tests in schools and increased testing in closed settings led to an earlier diagnosis and probably to a decreased transmission of the virus in the period during which Delta was the predominant variant in Greece. However, more effort is needed for early diagnosis of adults in the community, especially after the onset of symptoms