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"Pitigoi, Daniela"
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Ongoing measles outbreak in Romania: Clinical investigation and molecular epidemiology performed on whole genome sequences
2025
Romania is currently facing a prolonged measles outbreak. The aim of the study was to analyse the circulating human measles virus (HMV) strains by combining whole genome sequencing (WGS) with phylogenetic analysis, with a focus on the haemagglutinin gene.
We conducted an observational study in the first five months of 2024, in which 168 patients diagnosed with measles were randomly included. We have evaluated the clinical and epidemiological differences between children and adults. Screening for samples to be sequenced was performed with a commercial kit (PrimerDesign). WGS was done on Illumina MiSeq platform and phylogenetic analysis was performed with ML FastTree.
No significant epidemiological and clinical differences between patients in the two age groups were identified. WGS was successfully performed for a number of 124 HMV strains. Genotype analysis indicated all the sequences as D8, except one that was B3. Phylogenetic analysis identified two well supported clusters, suggestive for at least two local transmission networks in Romania. One large transmission network (n = 108) consisted of sequences both from adults and children. Only one sequence from outside Romania (reported in Russia in 2023) clustered within this group. Another small transmission cluster was identified (14 sequences of which 11 from patients infected in the spring of 2024 and three in 2022). A few differences between the two co-circulating viral variants/clusters were observed. The median duration of hospitalisation was 2 days longer for patients in smaller cluster compared to those in the larger one (p = 0.019). Furthermore, these two clusters presented different mutation profiles in the hemagglutinin (HA) and neuraminidase (N) genes with implications for molecular surveillance.
The current measles epidemic in Romania is driven mainly by two D8 genotype variants with different mutation profiles and slightly different severity of the disease, highlighting the usefulness of sustained molecular surveillance.
Journal Article
Clinical and molecular epidemiology of influenza viruses from Romanian patients hospitalized during the 2019/20 season
2021
Two main mechanisms contribute to the continuous evolution of influenza viruses: accumulation of mutations in the hemagglutinin and neuraminidase genes (antigenic drift) and genetic re-assortments (antigenic shift). Epidemiological surveillance is important in identifying new genetic variants of influenza viruses with potentially increased pathogenicity and transmissibility. In order to characterize the 2019/20 influenza epidemic in Romania, 1042 respiratory samples were collected from consecutive patients hospitalized with acute respiratory infections in the National Institute for Infectious Diseases “Prof. Dr. Matei Balș”, Bucharest Romania and tested for influenza A virus, influenza B virus and respiratory syncytial virus (RSV) by real-time PCR. Out of them, 516 cases were positive for influenza, with relatively equal distribution of influenza A and B. Two patients had influenza A and B co-infection and 8 patients had influenza-RSV co-infection. The most severe cases, requiring supplemental oxygen administration or intensive care, and the most deaths were reported in patients aged 65 years and over. Subtyping showed the predominance of A(H3N2) compared to A(H1N1)pdm09 pdm09 (60.4% and 39.6% of all subtyped influenza A isolates, respectively), and the circulation of Victoria B lineage only. Influenza B started to circulate first (week 47/2019), with influenza A appearing slightly later (week 50/2019), followed by continued co-circulation of A and B viruses throughout the season. Sixty-eight samples, selected to cover the entire influenza season and all circulating viral types, were analysed by next generation sequencing (NGS). All A(H1N1)pdm09 sequences identified during this season in Romania were clustered in the 6b1.A clade (sub-clades: 6b1.A.183P -5a and 6b1.A.187A). For most A(H1N1)pdm09 sequences, the dominant epitope was Sb (p epitope = 0.25), reducing the vaccine efficacy by approximately 60%. According to phylogenetic analysis, influenza A(H3N2) strains circulating in this season belonged predominantly to clade 3C.3A, with only few sequences in clade 3C.2A1b. These 3C.2A1b sequences, two of which belonged to vaccinated patients, harbored mutations in antigenic sites leading to potential reduction of vaccine efficacy. Phylogenetic analysis of influenza B, lineage Victoria, sequences showed that the circulating strains belonged to clade V1A3. As compared to the other viral types, fewer mutations were observed in B/Victoria strains, with limited impact on vaccine efficiency based on estimations.
Journal Article
Age, comorbidity burden and late presentation are significant predictors of hospitalization length and acute respiratory failure in patients with influenza
2024
Influenza viruses are responsible for a high number of infections and hospitalizations every year. In this study, we aimed to identify clinical and host-specific factors that influence the duration of hospitalization and the progression to acute respiratory failure (ARF) in influenza. We performed an analysis of data from a prospective active influenza surveillance study that was conducted over five seasons (2018/19 to 2022/23). A total of 1402 patients with influenza were included in the analysis, the majority of which (64.5%) were children (under 18 years), and 9.1% were elderly. At least one chronic condition was present in 29.2% of patients, and 9.9% of patients developed ARF. The median hospital stay was 4 days (IQR: 3, 6 days). The most important predictors of prolonged hospital stay and development of ARF were extremes of age (infants and elderly), presence of chronic diseases, particularly the cumulus of at least 3 chronic diseases, and late presentation to hospital. Among the chronic diseases, chronic obstructive pulmonary disease, cardiovascular disease, cancer, diabetes, obesity, and chronic kidney disease were strongly associated with a longer duration of hospitalization and occurrence of ARF. In this context, interventions aimed at chronic disease management, promoting influenza vaccination, and improving awareness and access to health services may contribute to reducing the impact of influenza not only in Romania but globally. In addition, continued monitoring of the circulation of influenza viruses is essential to limit their spread among vulnerable populations.
Journal Article
Etiology and Multi-Drug Resistant Profile of Bacterial Infections in Severe Burn Patients, Romania 2018–2022
by
Nițescu, Bogdan
,
Aramă, Victoria
,
Pițigoi, Daniela
in
Acinetobacter baumannii
,
Adult
,
Anti-Bacterial Agents - pharmacology
2023
Infections in severe burns and their etiology are and will remain a big concern for the medical field. The multi-drug resistant strains of bacteria are a challenge of today’s medicine. The aim of our study was to identify the etiological spectrum of bacterial infections in severe burn patients in Romania and their multi-drug resistant patterns. We performed a prospective study that included 202 adult patients admitted to the intensive care unit (ICU) of the Clinical Emergency Hospital of Plastic, Reconstructive Surgery and Burns, Bucharest, Romania (CEHPRSB), from 1 October 2018 to 1 April 2022, a period which includes the first 2 years of the outbreak of COVID-19. From each patient, wound swabs, endotracheal aspirates, blood for blood culture, and urine were collected. The most frequently isolated bacterium was Pseudomonas aeruginosa (39%), followed by Staphylococcus aureus (12%), Klebsiella spp. (11%), and Acinetobacter baumannii (9%). More than 90% of Pseudomonas aeruginosa and Acinetobacter baumannii were MDR, regardless of the clinical specimen from which they were isolated.
Journal Article
COVID-19 Vaccination in Romania and the Benefits of the National Electronic Registry of Vaccinations
by
Enciu, Bianca Georgiana
,
Pițigoi, Daniela
,
Popescu, Rodica
in
Adverse events
,
Confidentiality
,
Coronaviruses
2023
Background: Recording real-time data of vaccinations performed, vaccine stocks, and adverse events following immunization is a particularly useful activity in the effective development of any vaccination campaign or vaccination program, guiding the decisions of public health authorities. The aim of this paper is to present the benefits of the National Electronic Registry of Vaccinations in providing useful information for the optimization of healthcare vaccination policies, specifically related to COVID-19 vaccination. Methods: We performed a descriptive study using data available in the reports generated from the National Electronic Registry of Vaccinations regarding COVID-19 vaccinations performed between 27 December 2020 and 31 December 2021. Results: A total of 27,980,270 doses of the COVID-19 vaccine were distributed. Of these, 15,757,638 (56%) were administered in 4545 vaccination centers: 7,882,458 as the 1st dose (50%), 5,878,698 as the 2nd dose (37%), and 1,996,482 as the 3rd dose (13%). More than 25% of the total doses were administered to people over 65 years of age. A total of 41% of the population received at least one dose of the COVID-19 vaccine. A total of 4083 adverse events following immunization were reported. Conclusions: The existence of a National Electronic Registry of Vaccinations containing accurate information on vaccinations performed in Romania offers the opportunity to obtain a clear picture of vaccination status that will significantly contribute to the optimization of vaccination strategies and programs.
Journal Article
The 2017–2018 influenza season in Bucharest, Romania: epidemiology and characteristics of hospital admissions for influenza-like illness
2019
Background
Seasonal influenza causes a considerable burden to healthcare services every year. To better measure the impact of severe influenza cases in Romania, we analyzed active surveillance data collected during the 2017–2018 season from patients admitted for influenza-like illness (ILI) at a tertiary care hospital in Bucharest.
Methods
Patients admitted for acute ILI were included if they were resident in the Bucharest-Ilfov region, had been hospitalized for at least 24 h, and had onset of symptoms within 7 days before admission. Patient demographics, healthcare use, vaccination status, and outcome data were collected by questionnaire or by searching clinical records. Respiratory swabs were also obtained from each patient to confirm influenza A (A/H1 and A/H3 subtypes) or influenza B (Yamagata and Victoria lineages) infection by real-time reverse-transcription polymerase chain reaction assay.
Results
The study included 502 patients, many (45.2%) of whom were aged < 5 years. Overall, 108 patients (21.5%) had one or more comorbidities. Seventeen adults aged 18–64 years (3.4%) had been vaccinated against influenza. Patients were hospitalized for a median of 5 days and most (90.4%) were prescribed antiviral treatment. More than one-half of the patients (
n
= 259, 51.6%) were positive for influenza. Most influenza cases were caused by B viruses (172/259, 66.4%), which were mostly of the B/Yamagata lineage (85 of 94 characterized, 90.4%). Most of the subtyped A viruses were A/H1 (59/74, 79.7%). A/H1 viruses were frequently detected in influenza-positive admissions throughout the 2017–2018 season, whereas the predominant B/Yamagata viruses were detected around the middle of the season, with a peak in cases at week 7 of 2018. Eleven patients were admitted to an intensive care unit; of these, one patient with confirmed B/Yamagata infection died.
Conclusions
These results show that seasonal influenza results in considerable hospitalization in Bucharest-Ilfov, Romania and suggest vaccine coverage should be extended, especially to the youngest age groups. The data from this study should help inform and optimize national influenza healthcare policies.
Journal Article
Estimates of Pandemic Influenza Vaccine Effectiveness in Europe, 2009–2010: Results of Influenza Monitoring Vaccine Effectiveness in Europe (I-MOVE) Multicentre Case-Control Study
2011
A multicentre case-control study based on sentinel practitioner surveillance networks from seven European countries was undertaken to estimate the effectiveness of 2009-2010 pandemic and seasonal influenza vaccines against medically attended influenza-like illness (ILI) laboratory-confirmed as pandemic influenza A (H1N1) (pH1N1).
Sentinel practitioners swabbed ILI patients using systematic sampling. We included in the study patients meeting the European ILI case definition with onset of symptoms >14 days after the start of national pandemic vaccination campaigns. We compared pH1N1 cases to influenza laboratory-negative controls. A valid vaccination corresponded to >14 days between receiving a dose of vaccine and symptom onset. We estimated pooled vaccine effectiveness (VE) as 1 minus the odds ratio with the study site as a fixed effect. Using logistic regression, we adjusted VE for potential confounding factors (age group, sex, month of onset, chronic diseases and related hospitalizations, smoking history, seasonal influenza vaccinations, practitioner visits in previous year). We conducted a complete case analysis excluding individuals with missing values and a multiple multivariate imputation to estimate missing values. The multivariate imputation (n = 2902) adjusted pandemic VE (PIVE) estimates were 71.9% (95% confidence interval [CI] 45.6-85.5) overall; 78.4% (95% CI 54.4-89.8) in patients <65 years; and 72.9% (95% CI 39.8-87.8) in individuals without chronic disease. The complete case (n = 1,502) adjusted PIVE were 66.0% (95% CI 23.9-84.8), 71.3% (95% CI 29.1-88.4), and 70.2% (95% CI 19.4-89.0), respectively. The adjusted PIVE was 66.0% (95% CI -69.9 to 93.2) if vaccinated 8-14 days before ILI onset. The adjusted 2009-2010 seasonal influenza VE was 9.9% (95% CI -65.2 to 50.9).
Our results suggest good protection of the pandemic monovalent vaccine against medically attended pH1N1 and no effect of the 2009-2010 seasonal influenza vaccine. However, the late availability of the pandemic vaccine and subsequent limited coverage with this vaccine hampered our ability to study vaccine benefits during the outbreak period. Future studies should include estimation of the effectiveness of the new trivalent vaccine in the upcoming 2010-2011 season, when vaccination will occur before the influenza season starts.
Journal Article
A Severe Form of Mpox Infection and the Current Epidemiological Status in Romania
by
Cornovac, Alexandra
,
Stratan, Laurențiu
,
Molagic, Violeta
in
AIDS
,
Antiretroviral agents
,
Antiretroviral therapy
2025
Mpox has become a significant health concern since the global outbreak that began in 2022. The aim of this study is to present the epidemiological situation of Mpox in Romania during 2022–2023 and to describe a severe case of Mpox in a patient who survived despite multiple co-pathologies. Forty-seven confirmed cases were reported at the national level, all in men, in 2022. The median age was 33 years. Twenty-six cases involved men who have sex with men (MSM), and twenty-three tested positive for HIV. We also describe a severe case involving a 34-year-old bisexual male with newly diagnosed AIDS who developed severe Mpox with persistent necrotic skin lesions, respiratory involvement, and multiple opportunistic infections: tuberculosis, pneumocystis pneumonia, syphilis, and oral candidiasis. The patient presented with fever, night sweats, weight loss, and dyspnea, with a single ulcerative facial lesion that later disseminated. Mpox infection was confirmed through PCR from skin lesion, serum, saliva, urine, rectal, nasal, and pharyngeal swab samples, with high viral loads persisting despite prolonged Tecovirimat therapy. The patient developed immune reconstitution inflammatory syndrome following the initiation of antiretroviral therapy. This case emphasizes the challenges of treating Mpox in immunocompromised patients.
Journal Article
I-MOVE Multi-Centre Case Control Study 2010-11: Overall and Stratified Estimates of Influenza Vaccine Effectiveness in Europe
by
Ciancio, Bruno Christian
,
Kissling, Esther
,
Savulescu, Camelia
in
Adolescent
,
Adult
,
Age groups
2011
In the third season of I-MOVE (Influenza Monitoring Vaccine Effectiveness in Europe), we undertook a multicentre case-control study based on sentinel practitioner surveillance networks in eight European Union (EU) member states to estimate 2010/11 influenza vaccine effectiveness (VE) against medically-attended influenza-like illness (ILI) laboratory-confirmed as influenza.
Using systematic sampling, practitioners swabbed ILI/ARI patients within seven days of symptom onset. We compared influenza-positive to influenza laboratory-negative patients among those meeting the EU ILI case definition. A valid vaccination corresponded to > 14 days between receiving a dose of vaccine and symptom onset. We used multiple imputation with chained equations to estimate missing values. Using logistic regression with study as fixed effect we calculated influenza VE adjusting for potential confounders. We estimated influenza VE overall, by influenza type, age group and among the target group for vaccination.
We included 2019 cases and 2391 controls in the analysis. Adjusted VE was 52% (95% CI 30-67) overall (N = 4410), 55% (95% CI 29-72) against A(H1N1) and 50% (95% CI 14-71) against influenza B. Adjusted VE against all influenza subtypes was 66% (95% CI 15-86), 41% (95% CI -3-66) and 60% (95% CI 17-81) among those aged 0-14, 15-59 and ≥60 respectively. Among target groups for vaccination (N = 1004), VE was 56% (95% CI 34-71) overall, 59% (95% CI 32-75) against A(H1N1) and 63% (95% CI 31-81) against influenza B.
Results suggest moderate protection from 2010-11 trivalent influenza vaccines against medically-attended ILI laboratory-confirmed as influenza across Europe. Adjusted and stratified influenza VE estimates are possible with the large sample size of this multi-centre case-control. I-MOVE shows how a network can provide precise summary VE measures across Europe.
Journal Article
Clostridioides difficile Infections and Antibiotherapy: Results of Four Years of Observation in a Romanian Tertiary Hospital
by
Pițigoi, Daniela
,
Vasile, Carmen-Cristina
,
Chivu, Carmen-Daniela
in
antibiotherapy
,
Antibiotics
,
Carbapenems
2024
Clostridioides difficile infection (CDI) is one of the main causes of morbidity associated with antibiotic use, producing both healthcare-associated infections and community infections. This study aims to describe the epidemiological characteristics, the clinical outcomes, previous antibiotic exposure, and other risk factors of hospitalized patients with CDI in a tertiary infectious disease hospital in Bucharest, Romania. We performed a descriptive analysis based on four-year surveillance data, collected in a tertiary infectious disease hospital in Bucharest, Romania. The annual incidence of CDIs varied from 65.1 cases per 10,000 discharges in 2020 to 211.7 cases per 10,000 discharges in 2023, with a continuously ascending trend. Most of the cases were hospital-acquired cases. There was a high share of antibiotic consumption three months before admission (61.3%). Third-generation cephalosporins, β-lactams with inhibitor combination, and carbapenems were the most used antibiotics, with shares of 46.0%, 25.2%, and 18.6%, respectively. Hospitalization in the previous 12 months and contact with a confirmed CDI case were other frequent factors in the study group, the occurrences of which were recorded as 66.2% and 2.4%, respectively. The surveillance data identified that the annual trend in CDIs is very variable, suggesting the need for continuous and multiannual analysis.
Journal Article