Raluca Jipa - Academia.edu (original) (raw)

Papers by Raluca Jipa

Research paper thumbnail of Exhaustion and senescence of CD4 and CD8 T cells that express co-stimulatory molecules CD27 and CD28 in subjects that acquired HIV by drug use or by sexual route

Research paper thumbnail of Long-Term Longitudinal Evaluation of Six Commercial Immunoassays for the Detection of IgM and IgG Antibodies against SARS CoV-2

Viruses, Jun 26, 2021

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of POSTER PRESENTATION Open Access Characteristics of Kaposi sarcoma in HIV-infected

Objective: to describe clinical and laboratory characteris-tics; to assess predictors for death i... more Objective: to describe clinical and laboratory characteris-tics; to assess predictors for death in HIV-infected patients with Kaposi sarcoma (KS). We performed a retrospective study of HIV-infected patients diagnosed with KS in one infectious diseases hos-pital in Romania, between January 2008-November 2013. KS diagnosis was established on physical examination, skin biopsy, and for visceral involvement upper gastroin-testinal endoscopy, bronchoscopy and computed tomogra-phy. KS was staged according to the AIDS Clinical Trials Group (ACTG) [1] and the Mitsuyasu classification system [2]. We identified 27 HIV-infected patients with KS. The median age was 42 years (IQR 34-52) and 18 (67%) were male. The median CD4 count at HIV diagnosis was 195

Research paper thumbnail of Cost-Efficacy of Antiretroviral Regimens Recommended in Treatment-Naive HIV-Infected Adults. A Single Center Experience

We aimed to assess the prescription trends of combined antiretroviral therapy (cART) in one infec... more We aimed to assess the prescription trends of combined antiretroviral therapy (cART) in one infectious diseases department and the cost-efficacy (C/E) of different regimens used in treatment-naive patients. The C/E was assessed with a software application developed by a group of researchers in Spain. The efficacy was already calculated in the application. The costs included the local cost of antiretrovirals and other direct costs specific to our institution. In the software application, the C/E reference regimen was ABC/3TC/DTG. In total, 181 HIV-infected patients were diagnosed and initiated cART during 2015–2019. The proportion of patients treated with integrase-strand transfer inhibitor (INSTI)-based regimens increased from 2015–2018 (54%) to the end of 2019 (81%). The relative C/E ranged from 0.90 to 1.28 for the evaluated INSTI-based regimens. Among INSTI-based regimens, ABC/3TC/DTG and TAF/FTC/EVG/c are the regimens with similar efficacy and relative C/E.

Research paper thumbnail of Safety assessment in Child A cirrhotic patients treated with Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir with Ribavirin

Acta gastro-enterologica Belgica, 2018

BACKGROUND In our country, the national program for hepatitis C virus treatment with ombitasvir/p... more BACKGROUND In our country, the national program for hepatitis C virus treatment with ombitasvir/paritaprevir/ritonavir and dasabuvir was approved for patients with stage four of liver fibrosis and stage three associated with specific comorbidities. Our aim was to analyze the characteristics associated with the presence of adverse events in patients receiving this antiviral regimen, with ribavirin in cirrhotic patients. METHODS We prospectively studied a cohort of adults with hepatitis C virus infection with Child A cirrhosis, treated for 12 weeks with ombitasvir/paritaprevir/ritonavir/dasabuvir and ribavirin, which have been followed in an infectious diseases tertiary-care hospital. RESULTS We included 137 adult patients diagnosed with compensated cirrhosis, hepatitis C virus genotype 1b infected, 82 (60%) previously treated. We recorded 201 adverse events in 98 (71.5%) patients, with a median number of events per patient of one. The intensity of adverse events was classified as mil...

Research paper thumbnail of Long-Term Longitudinal Evaluation of Six Commercial Immunoassays for the Detection of IgM and IgG Antibodies against SARS CoV-2

Viruses, 2021

The number of serological assays for SARS-CoV-2 has skyrocketed in the past year. Concerns have b... more The number of serological assays for SARS-CoV-2 has skyrocketed in the past year. Concerns have been raised regarding their performance characteristics, depending on the disease severity and the time of the analysis post-symptom onset (PSO). Thus, independent validations using an unbiased sample selection are required for meaningful serology data interpretation. We aimed to assess the clinical performance of six commercially available assays, the seroconversion, and the dynamics of the humoral response to SARS-CoV-2 infection. The study included 528 serum samples from 156 patients with follow-up visits up to six months PSO and 161 serum samples from healthy people. The IgG/total antibodies positive percentage increased and remained above 95% after six months when chemiluminescent immunoassay (CLIA) IgG antiS1/S2 and electro-chemiluminescent assay (ECLIA) total antiNP were used. At early time points PSO, chemiluminescent microparticle immunoassay (CMIA) IgM antiS achieved the best se...

Research paper thumbnail of Tuberculosis in people living with human immunodeficiency virus might be overlooked

Romanian Journal of Legal Medicine, 2019

Research paper thumbnail of HIV outbreaks among people who inject drugs in Europe, North America, and Israel

The Lancet HIV, 2020

During 2011-2016, HIV outbreaks occurred among people who inject drugs (PWID) in

Research paper thumbnail of Rapid clinical score for the diagnosis of tuberculous meningitis: A retrospective cohort study

Annals of Indian Academy of Neurology, 2017

IntroductIon The outcome of tuberculous meningitis (TBM) is greatly influenced by the time to tre... more IntroductIon The outcome of tuberculous meningitis (TBM) is greatly influenced by the time to treatment initiation. Therefore, establishing a rapid diagnosis is crucial. A rapid clinical score (RCS) was found to have good sensitivity and specificity in differentiating TBM from viral meningitis (VM). [1] The aim of our study was to retrospectively validate the RCS in distinguishing TBM from VM in people who are at increased risk of tuberculosis and evaluate its performance in differentiating TBM from cryptococcal meningitis (CM). Methods We performed a retrospective study of patients admitted with a diagnosis of aseptic meningitis between January 2012 and December 2015, to a referral hospital for infectious diseases, from Bucharest, Romania. We reviewed medical records of all adults with clinical symptoms of meningitis (fever, headache, nausea/vomiting, neck stiffness), who had a clear appearance of cerebrospinal fluid (CSF) and abnormal CSF findings: pleocytosis ≥5 cells/mm 3 , the absence of bacteria either on Gram stain and/or in routine culture, and/or negative latex agglutination tests for bacterial antigens. Patients were considered to have definite TBM if they had a microbiological confirmation of Mycobacterium tuberculosis from a CSF sample by either detection of acid-fast bacilli on CSF smear, positive culture for M. tuberculosis, and/or positive GeneXpert MTB/RIF (Cepheid, Sunnyvale, USA). Probable Objective: The aim of our study was to retrospectively validate a previously described rapid clinical score (RCS) in distinguishing tuberculous meningitis (TBM) from viral meningitis (VM) in people who are at increased risk of tuberculosis, as well as from cryptococcal meningitis (CM) in HIV-infected patients. Methods: We performed a retrospective study of patients admitted with a diagnosis of aseptic meningitis between January 2012 and December 2015, to a referral hospital for infectious diseases. The variables included in RCS were duration of symptoms before admission, neurological stage, cerebrospinal fluid (CSF) to blood glucose ratio, and CSF protein. We included in this retrospective study 31 patients with definite or probable TBM including 14 HIV-infected patients, 62 HIV-noninfected patients with VM, and 18 HIV-infected patients with CM. Results: The sensitivity of RCS to distinguish TBM from VM was 96.7%, with a specificity of 81.1% and the area under the receiver operating characteristic (ROC) curve was 0.949 (0.90-0.99). When all four criteria from the RCS were present, the specificity increased at 100%. In HIV-infected patients, the sensitivity and specificity of RCS in differentiating TBM from CM were 86.6% and 27.7%, respectively, and the area under the ROC curve was 0.669 (0.48-0.85). Conclusion: This easy-to-use RCS was found to be helpful in differentiating TBM from VM, with a better sensitivity than molecular amplification techniques and a relatively good specificity. However, the RCS was not useful to differentiate between TBM and CM in HIV-infected patients.

Research paper thumbnail of A16 Next-generation sequencing to detect transmitted drug resistance mutations in Romanian people who inject drugs

Virus Evolution, 2019

Romania has faced an HIV outbreak among people who inject drugs (PWID) since 2011. The introducti... more Romania has faced an HIV outbreak among people who inject drugs (PWID) since 2011. The introduction of so-called ‘legal highs’ (amphetamine-type stimulants) on the drug market a few years prior contributed substantially to this outbreak. Next-generation sequencing (NGS) provides the possibility to detect drug resistance mutations with higher sensitivity than Sanger sequencing. The aim of this study was to search for transmitted drug resistance (TDR) mutations in strains from PWID recently diagnosed with HIV infection by parallel use of Sanger sequencing and NGS. The study was conducted on strains from 34 PWID diagnosed with HIV infection between 2016 and 2017. Sequencing was performed for the pol (PR, RT, and INT) and env (V2-V3 loop) regions. Sanger sequencing was performed with the commercial ViroseqTMHIV-1 Genotyping system (Abbott Laboratories) and with an in-house protocol for the env gene. NGS was performed in the same genomic regions using Nextera DNA Library Preparation Kit ...

Research paper thumbnail of Epidemic dispersion of HIV and HCV in a population of co-infected Romanian injecting drug users

PLOS ONE, 2017

Co-infections with HIV and HCV are very frequent among people who inject drugs (PWID). However, v... more Co-infections with HIV and HCV are very frequent among people who inject drugs (PWID). However, very few studies comparatively reconstructed the transmission patterns of both viruses in the same population. We have recruited 117 co-infected PWID during a recent HIV outbreak in Romania. Phylogenetic analyses were performed on HIV and HCV sequences in order to characterize and compare transmission dynamics of the two viruses. Three large HIV clusters (2 subtype F1 and one CRF14_BG) and thirteen smaller HCV transmission networks (genotypes 1a, 1b, 3a, 4a and 4d) were identified. Eighty (65%) patients were both in HIV and HCV transmission chains and 70 of those shared the same HIV and HCV cluster with at least one other patient. Molecular clock analysis indicated that all identified HIV clusters originated around 2006, while the origin of the different HCV clusters ranged between 1980 (genotype 1b) and 2011 (genotypes 3a and 4d). HCV infection preceded HIV infection in 80.3% of cases. Coincidental transmission of HIV and HCV was estimated to be rather low (19.65%) and associated with an outbreak among PWID during detention in the same penitentiary. This study has reconstructed and compared the dispersion of these two viruses in a PWID population.

Research paper thumbnail of The role of Tigecycline in the management of Clostridium difficile infection: a retrospective cohort study

Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, Jan 19, 2017

We aimed to compare the outcomes of patients with C.difficile infection (CDI) treated either with... more We aimed to compare the outcomes of patients with C.difficile infection (CDI) treated either with tigecycline associated with vancomycin, or with vancomycin alone. This single-centre retrospective cohort study included all adults hospitalized from September 2014 through August 2015 for symptomatic, incident CDI confirmed by polymerase chain reaction for C.difficile toxin in stools. The primary outcome was the rate of favourable outcome, defined as a composite of clinical response (resolution of symptoms without need for additional CDI therapy) and achieving discharge without CDI-related surgery or intensive care; a secondary outcome was CDI recurrence. We constructed a non-parsimonious logistic regression model to calculate a propensity score (PS) for those receiving tigecycline. In all, 266 patients were included: 62 patients received both vancomycin and tigecycline, and 204 patients received vancomycin alone. The patients from the two groups were similar regarding demographics and...

Research paper thumbnail of The 12th Edition of the Scientific Days of the National Institute for Infectious Diseases “Prof. Dr. Matei Bals” and the 12th National Infectious Diseases Conference

BMC Infectious Diseases, 2016

Background Pneumococcal meningitis (PM) is a life-threatening disease. Recurrent PM is relatively... more Background Pneumococcal meningitis (PM) is a life-threatening disease. Recurrent PM is relatively rare and associated with predisposing conditions. This study analyzed the outcome of patients with recurrent versus non-recurrent PM. Methods We conducted a retrospective study, analyzing the records of all the patients hospitalized between 2005 and 2015 for PM in our institution. We included patients with the diagnostic of PM based on appearance on Gram stain, a positive latex agglutination reaction of cerebral spinal fluid (CSF) samples and/or a positive culture for Streptococcus pneumoniae (CSF culture or blood culture and concomitant meningitis). We defined "recurrent meningitis" as at least two episodes of meningitis, separated by a period of at least 4 weeks. Results We identified a total of 194 PM episodes in 182 patients. Thirty eight (20 %) patients were diagnosed with recurrent meningitis, and they had 93 prior episodes recorded. The majority of patients with recurrent meningitis experienced two meningitis episodes, but we found 3 patients with 7, 11 and 40 recurrent episodes. Nineteen (50 %) patients in recurrent meningitis group and 90 (58 %) in non-recurrent group were men. Median age of patients with recurrent versus non-recurrent meningitis was 29 versus 57 years (p < 0.001). Nine (24 %) patients with recurrent meningitis versus 64 (41 %) patients with non-recurrent meningitis had an underlying immunosuppressive condition (p = 0.02, OR:0.41, 95 % CI:0.18-0.92). The immunosuppression was: diabetes mellitus in 32 (44 %), alcoholism in 19 (26 %), endstage liver disease in 7 (9.5 %) and malignancy, malnutrition, pregnancy, splenectomy and immunosuppressive therapy in 15 (20.5 %). We found dissemination of infection from a contiguous site in 74 (38 %) cases, bone defects and/or CSF leakage in 36 (18.5 %) cases and hematogenous spread in 14 (7.2 %) cases. A cranial bone discontinuity and/or CSF leakage were identified in recurrent versus non-recurrent meningitis in 21 (55 %) versus 15 (10 %) episodes (p < 0.001, OR:14.41, 95 % CI:6.21-33.4). Hematogenous spread was observed only in the non-recurrent meningitis group. In recurrent versus nonrecurrent meningitis, impaired consciousness on admission was noted in 15 (40 %) versus 64 (41 %). We noted one death (2.6 %) among patients with recurrent PM group vs 42 (27 %) in the non-recurrent group (p<0.001, OR:0.07, 95 % CI:0.01-0.5). Death was associated with nonrecurrent meningitis (p < 0.001), contiguous spread (p = 0.014), immunodepression (p = 0.01) and impaired consciousness (p = 0.005). Conclusions Patients with recurrent meningitis were younger, with less immunosuppression conditions and had a better survival versus those with non-recurrent meningitis. Mortality of PM was associated with immunosuppression and impaired consciousness, but the small number of deaths in the recurrent group did not allow us to analyses the differences between the two groups.

Research paper thumbnail of Proceedings of The 8th Romanian National HIV/AIDS Congress and The 3rd Central European HIV Forum

BMC Infectious Diseases, 2016

Objectives In Bulgaria 1606 cases with HIV/AIDS were diagnosed from 1986 until 2012. Epidemiologi... more Objectives In Bulgaria 1606 cases with HIV/AIDS were diagnosed from 1986 until 2012. Epidemiological data indicated greater heterogeneity of HIV-1 positive population, including minority groups, migrants, and recent increase of men who have sex with men (MSM) and intravenous drug users (IDUs). The aim of the present study was to investigate the current molecular epidemiological picture of HIV-1 diversity among different transmission groups in Bulgaria. Materials and Methods HIV-1 diversity was analyzed in 637 (39.7 %) of all HIV/AIDS patients in the country. HIV-1 pol sequences were generated with TruGene and/or ViroSeq Genotyping Systems. The sequence alignment contained Bulgarian sequences and reference sequences from Los Alamos and GenBank. Phylogenetic relationships were inferred by ML and Bayesian analysis. Recombinations were analyzed with bootscan analysis using SimPlot software. Results The most prevalent HIV-1 strain in the studied population was found to be subtype B 38.8 %. That strain was followed by CRF01_AE 20.3 %, CRF02_AG 13.8 %, subtype C 3.6 %, subtype A1 1.6 % and the rest of strains were defined as 3 different HIV-1 subtypes (F, G and H) and 7 circulating recombinant forms (05_DF, 14_BG, 03_AB, 04_cpx, 12_BF, 33_01B and 36_cpx). In addition, 30 different unique recombinant forms consisting of 18.2 % were identified. We found that unlike in the most European countries, where subtype B is dominating, non-B HIV-1 subtypes were the most prevalent in Bulgaria. Phylogenetic analysis showed multiple clusters demonstrating rapid development of sub-epidemics in different transmission groups. In addition, unequal distribution of HIV-1 clades across different regions and transmission groups of the populations were found. Moreover, we found that various viral clades were introduced in Bulgaria from abroad by migrants. Conclusions Our analysis revealed wide HIV-1 diversity and unequal distribution of different strains among MSM, IDUs and heterosexual individuals. Phylogenetic analysis showed multiple clusters demonstrating development of local-epidemics. Significant number of HIV-1 clades were introduced from abroad by migrants. Our findings indicated that providing of detailed molecular epidemiological surveillance of HIV-1 in Bulgaria is of great importance to better understand the epidemic in the country.

Research paper thumbnail of Kaposi Sarcoma in HIV Infected Patients

Acta Medica Marisiensis, 2016

The aim of the study was to describe clinical and laboratory characteristics in HIV-infected pati... more The aim of the study was to describe clinical and laboratory characteristics in HIV-infected patients with Kaposi sarcoma (KS). Methods: We retrospectively studied data on HIV-infected patients hospitalized in one tertiary care hospital in Bucharest, Romania, in whom Kaposi Sarcoma was diagnosed, between January 2008 and November 2013. Results: We identified 27 HIV-infected patients diagnosed with KS within 6 years. They had a median age of 42 years old and a median CD4 cell count of 101 cells per mm 3 at the time of KS diagnosis. All patients received antiretroviral therapy (ART), with 18 patients (66%) already on ART at the time of KS diagnosis. Most patients (59%) were classified as ACTG poor-risk and 56% as Mitsuyasu stage I. The overall prognosis was poor, with 41% mortality, in a median time span of 6 months, significantly correlated with gastrointestinal involvement (p=0.019), poor-risk KS in ACTG classification (p<0.001) and stage IV Mitsuyasu (p=0.006). Conclusion: KS remains an important cause of morbidity and mortality in patients with HIV infection, especially in late presenters.

Research paper thumbnail of Knowledge, attitudes and practices of Romanian international travellers concerning travel-related infectious diseases and vaccinations

Research paper thumbnail of The Role of Ethnobotanical Drugs on the Recent Outbreak of Right-sided Endocarditis in Romania

Journal of gastrointestinal and liver diseases: JGLD

Background. Romania is facing a recent outbreak of infective endocarditis (IE) in injecting drug ... more Background. Romania is facing a recent outbreak of infective endocarditis (IE) in injecting drug users (IDUs). This started in 2010, after the introduction of the ethnobotanical drugs. This study explores the features of this outbreak. Methods. Retrospective study of IDU patients with IE hospitalized in the 􀀱􀁄􀁗􀁌􀁒􀁑􀁄􀁏􀀃 􀀬􀁑􀁖􀁗􀁌􀁗􀁘􀁗􀁈􀀃 􀁒􀁉􀀃 􀀬􀁑􀁉􀁈􀁆􀁗􀁌􀁒􀁘􀁖􀀃 􀀧􀁌􀁖􀁈􀁄􀁖􀁈􀁖􀀃 􀂳􀀳􀁕􀁒􀁉􀀑􀀃 􀀧􀁕􀀑􀀃 􀀰􀁄􀁗􀁈􀁌􀀃 􀀥􀁄􀁏􀃺􀂴 between 2007 and September 2012. Results. We identified 45 patients, out of which 30 were men (M/F=2), with a median age of 29 years. Thirty-seven (82%) used heroin (with a median duration of 10 years), 32 (71%) consumed ethnobotanical drugs (with a median duration of 1 year) and 24 (53%) used both drugs. Twelve cases of IE in IDUs were diagnosed in the first 9 months of 2012, 21 in 2011, 10 in 2010 and only 2 cases between 2007 and 2010. Tricuspid valve endocarditis (TVE) was diagnosed in 37 (83%) cases; the most common pathogen isolated in 31 (70%) blood cultures was Staphylococcus aureus (18 MRSA). Multip...

Research paper thumbnail of Efficacy of peginterferon alfa 2a treatment in Romanian patients with chronic hepatitis D

Research paper thumbnail of Co-infections and co-morbidities among injecting drug users versus sexually infected patients in Bucharest

Journal of the International AIDS Society, 2014

Research paper thumbnail of Initiating the antiretroviral therapy in treatment-naïve patients

BMC Infectious Diseases, 2014

Research paper thumbnail of Exhaustion and senescence of CD4 and CD8 T cells that express co-stimulatory molecules CD27 and CD28 in subjects that acquired HIV by drug use or by sexual route

Research paper thumbnail of Long-Term Longitudinal Evaluation of Six Commercial Immunoassays for the Detection of IgM and IgG Antibodies against SARS CoV-2

Viruses, Jun 26, 2021

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of POSTER PRESENTATION Open Access Characteristics of Kaposi sarcoma in HIV-infected

Objective: to describe clinical and laboratory characteris-tics; to assess predictors for death i... more Objective: to describe clinical and laboratory characteris-tics; to assess predictors for death in HIV-infected patients with Kaposi sarcoma (KS). We performed a retrospective study of HIV-infected patients diagnosed with KS in one infectious diseases hos-pital in Romania, between January 2008-November 2013. KS diagnosis was established on physical examination, skin biopsy, and for visceral involvement upper gastroin-testinal endoscopy, bronchoscopy and computed tomogra-phy. KS was staged according to the AIDS Clinical Trials Group (ACTG) [1] and the Mitsuyasu classification system [2]. We identified 27 HIV-infected patients with KS. The median age was 42 years (IQR 34-52) and 18 (67%) were male. The median CD4 count at HIV diagnosis was 195

Research paper thumbnail of Cost-Efficacy of Antiretroviral Regimens Recommended in Treatment-Naive HIV-Infected Adults. A Single Center Experience

We aimed to assess the prescription trends of combined antiretroviral therapy (cART) in one infec... more We aimed to assess the prescription trends of combined antiretroviral therapy (cART) in one infectious diseases department and the cost-efficacy (C/E) of different regimens used in treatment-naive patients. The C/E was assessed with a software application developed by a group of researchers in Spain. The efficacy was already calculated in the application. The costs included the local cost of antiretrovirals and other direct costs specific to our institution. In the software application, the C/E reference regimen was ABC/3TC/DTG. In total, 181 HIV-infected patients were diagnosed and initiated cART during 2015–2019. The proportion of patients treated with integrase-strand transfer inhibitor (INSTI)-based regimens increased from 2015–2018 (54%) to the end of 2019 (81%). The relative C/E ranged from 0.90 to 1.28 for the evaluated INSTI-based regimens. Among INSTI-based regimens, ABC/3TC/DTG and TAF/FTC/EVG/c are the regimens with similar efficacy and relative C/E.

Research paper thumbnail of Safety assessment in Child A cirrhotic patients treated with Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir with Ribavirin

Acta gastro-enterologica Belgica, 2018

BACKGROUND In our country, the national program for hepatitis C virus treatment with ombitasvir/p... more BACKGROUND In our country, the national program for hepatitis C virus treatment with ombitasvir/paritaprevir/ritonavir and dasabuvir was approved for patients with stage four of liver fibrosis and stage three associated with specific comorbidities. Our aim was to analyze the characteristics associated with the presence of adverse events in patients receiving this antiviral regimen, with ribavirin in cirrhotic patients. METHODS We prospectively studied a cohort of adults with hepatitis C virus infection with Child A cirrhosis, treated for 12 weeks with ombitasvir/paritaprevir/ritonavir/dasabuvir and ribavirin, which have been followed in an infectious diseases tertiary-care hospital. RESULTS We included 137 adult patients diagnosed with compensated cirrhosis, hepatitis C virus genotype 1b infected, 82 (60%) previously treated. We recorded 201 adverse events in 98 (71.5%) patients, with a median number of events per patient of one. The intensity of adverse events was classified as mil...

Research paper thumbnail of Long-Term Longitudinal Evaluation of Six Commercial Immunoassays for the Detection of IgM and IgG Antibodies against SARS CoV-2

Viruses, 2021

The number of serological assays for SARS-CoV-2 has skyrocketed in the past year. Concerns have b... more The number of serological assays for SARS-CoV-2 has skyrocketed in the past year. Concerns have been raised regarding their performance characteristics, depending on the disease severity and the time of the analysis post-symptom onset (PSO). Thus, independent validations using an unbiased sample selection are required for meaningful serology data interpretation. We aimed to assess the clinical performance of six commercially available assays, the seroconversion, and the dynamics of the humoral response to SARS-CoV-2 infection. The study included 528 serum samples from 156 patients with follow-up visits up to six months PSO and 161 serum samples from healthy people. The IgG/total antibodies positive percentage increased and remained above 95% after six months when chemiluminescent immunoassay (CLIA) IgG antiS1/S2 and electro-chemiluminescent assay (ECLIA) total antiNP were used. At early time points PSO, chemiluminescent microparticle immunoassay (CMIA) IgM antiS achieved the best se...

Research paper thumbnail of Tuberculosis in people living with human immunodeficiency virus might be overlooked

Romanian Journal of Legal Medicine, 2019

Research paper thumbnail of HIV outbreaks among people who inject drugs in Europe, North America, and Israel

The Lancet HIV, 2020

During 2011-2016, HIV outbreaks occurred among people who inject drugs (PWID) in

Research paper thumbnail of Rapid clinical score for the diagnosis of tuberculous meningitis: A retrospective cohort study

Annals of Indian Academy of Neurology, 2017

IntroductIon The outcome of tuberculous meningitis (TBM) is greatly influenced by the time to tre... more IntroductIon The outcome of tuberculous meningitis (TBM) is greatly influenced by the time to treatment initiation. Therefore, establishing a rapid diagnosis is crucial. A rapid clinical score (RCS) was found to have good sensitivity and specificity in differentiating TBM from viral meningitis (VM). [1] The aim of our study was to retrospectively validate the RCS in distinguishing TBM from VM in people who are at increased risk of tuberculosis and evaluate its performance in differentiating TBM from cryptococcal meningitis (CM). Methods We performed a retrospective study of patients admitted with a diagnosis of aseptic meningitis between January 2012 and December 2015, to a referral hospital for infectious diseases, from Bucharest, Romania. We reviewed medical records of all adults with clinical symptoms of meningitis (fever, headache, nausea/vomiting, neck stiffness), who had a clear appearance of cerebrospinal fluid (CSF) and abnormal CSF findings: pleocytosis ≥5 cells/mm 3 , the absence of bacteria either on Gram stain and/or in routine culture, and/or negative latex agglutination tests for bacterial antigens. Patients were considered to have definite TBM if they had a microbiological confirmation of Mycobacterium tuberculosis from a CSF sample by either detection of acid-fast bacilli on CSF smear, positive culture for M. tuberculosis, and/or positive GeneXpert MTB/RIF (Cepheid, Sunnyvale, USA). Probable Objective: The aim of our study was to retrospectively validate a previously described rapid clinical score (RCS) in distinguishing tuberculous meningitis (TBM) from viral meningitis (VM) in people who are at increased risk of tuberculosis, as well as from cryptococcal meningitis (CM) in HIV-infected patients. Methods: We performed a retrospective study of patients admitted with a diagnosis of aseptic meningitis between January 2012 and December 2015, to a referral hospital for infectious diseases. The variables included in RCS were duration of symptoms before admission, neurological stage, cerebrospinal fluid (CSF) to blood glucose ratio, and CSF protein. We included in this retrospective study 31 patients with definite or probable TBM including 14 HIV-infected patients, 62 HIV-noninfected patients with VM, and 18 HIV-infected patients with CM. Results: The sensitivity of RCS to distinguish TBM from VM was 96.7%, with a specificity of 81.1% and the area under the receiver operating characteristic (ROC) curve was 0.949 (0.90-0.99). When all four criteria from the RCS were present, the specificity increased at 100%. In HIV-infected patients, the sensitivity and specificity of RCS in differentiating TBM from CM were 86.6% and 27.7%, respectively, and the area under the ROC curve was 0.669 (0.48-0.85). Conclusion: This easy-to-use RCS was found to be helpful in differentiating TBM from VM, with a better sensitivity than molecular amplification techniques and a relatively good specificity. However, the RCS was not useful to differentiate between TBM and CM in HIV-infected patients.

Research paper thumbnail of A16 Next-generation sequencing to detect transmitted drug resistance mutations in Romanian people who inject drugs

Virus Evolution, 2019

Romania has faced an HIV outbreak among people who inject drugs (PWID) since 2011. The introducti... more Romania has faced an HIV outbreak among people who inject drugs (PWID) since 2011. The introduction of so-called ‘legal highs’ (amphetamine-type stimulants) on the drug market a few years prior contributed substantially to this outbreak. Next-generation sequencing (NGS) provides the possibility to detect drug resistance mutations with higher sensitivity than Sanger sequencing. The aim of this study was to search for transmitted drug resistance (TDR) mutations in strains from PWID recently diagnosed with HIV infection by parallel use of Sanger sequencing and NGS. The study was conducted on strains from 34 PWID diagnosed with HIV infection between 2016 and 2017. Sequencing was performed for the pol (PR, RT, and INT) and env (V2-V3 loop) regions. Sanger sequencing was performed with the commercial ViroseqTMHIV-1 Genotyping system (Abbott Laboratories) and with an in-house protocol for the env gene. NGS was performed in the same genomic regions using Nextera DNA Library Preparation Kit ...

Research paper thumbnail of Epidemic dispersion of HIV and HCV in a population of co-infected Romanian injecting drug users

PLOS ONE, 2017

Co-infections with HIV and HCV are very frequent among people who inject drugs (PWID). However, v... more Co-infections with HIV and HCV are very frequent among people who inject drugs (PWID). However, very few studies comparatively reconstructed the transmission patterns of both viruses in the same population. We have recruited 117 co-infected PWID during a recent HIV outbreak in Romania. Phylogenetic analyses were performed on HIV and HCV sequences in order to characterize and compare transmission dynamics of the two viruses. Three large HIV clusters (2 subtype F1 and one CRF14_BG) and thirteen smaller HCV transmission networks (genotypes 1a, 1b, 3a, 4a and 4d) were identified. Eighty (65%) patients were both in HIV and HCV transmission chains and 70 of those shared the same HIV and HCV cluster with at least one other patient. Molecular clock analysis indicated that all identified HIV clusters originated around 2006, while the origin of the different HCV clusters ranged between 1980 (genotype 1b) and 2011 (genotypes 3a and 4d). HCV infection preceded HIV infection in 80.3% of cases. Coincidental transmission of HIV and HCV was estimated to be rather low (19.65%) and associated with an outbreak among PWID during detention in the same penitentiary. This study has reconstructed and compared the dispersion of these two viruses in a PWID population.

Research paper thumbnail of The role of Tigecycline in the management of Clostridium difficile infection: a retrospective cohort study

Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, Jan 19, 2017

We aimed to compare the outcomes of patients with C.difficile infection (CDI) treated either with... more We aimed to compare the outcomes of patients with C.difficile infection (CDI) treated either with tigecycline associated with vancomycin, or with vancomycin alone. This single-centre retrospective cohort study included all adults hospitalized from September 2014 through August 2015 for symptomatic, incident CDI confirmed by polymerase chain reaction for C.difficile toxin in stools. The primary outcome was the rate of favourable outcome, defined as a composite of clinical response (resolution of symptoms without need for additional CDI therapy) and achieving discharge without CDI-related surgery or intensive care; a secondary outcome was CDI recurrence. We constructed a non-parsimonious logistic regression model to calculate a propensity score (PS) for those receiving tigecycline. In all, 266 patients were included: 62 patients received both vancomycin and tigecycline, and 204 patients received vancomycin alone. The patients from the two groups were similar regarding demographics and...

Research paper thumbnail of The 12th Edition of the Scientific Days of the National Institute for Infectious Diseases “Prof. Dr. Matei Bals” and the 12th National Infectious Diseases Conference

BMC Infectious Diseases, 2016

Background Pneumococcal meningitis (PM) is a life-threatening disease. Recurrent PM is relatively... more Background Pneumococcal meningitis (PM) is a life-threatening disease. Recurrent PM is relatively rare and associated with predisposing conditions. This study analyzed the outcome of patients with recurrent versus non-recurrent PM. Methods We conducted a retrospective study, analyzing the records of all the patients hospitalized between 2005 and 2015 for PM in our institution. We included patients with the diagnostic of PM based on appearance on Gram stain, a positive latex agglutination reaction of cerebral spinal fluid (CSF) samples and/or a positive culture for Streptococcus pneumoniae (CSF culture or blood culture and concomitant meningitis). We defined "recurrent meningitis" as at least two episodes of meningitis, separated by a period of at least 4 weeks. Results We identified a total of 194 PM episodes in 182 patients. Thirty eight (20 %) patients were diagnosed with recurrent meningitis, and they had 93 prior episodes recorded. The majority of patients with recurrent meningitis experienced two meningitis episodes, but we found 3 patients with 7, 11 and 40 recurrent episodes. Nineteen (50 %) patients in recurrent meningitis group and 90 (58 %) in non-recurrent group were men. Median age of patients with recurrent versus non-recurrent meningitis was 29 versus 57 years (p < 0.001). Nine (24 %) patients with recurrent meningitis versus 64 (41 %) patients with non-recurrent meningitis had an underlying immunosuppressive condition (p = 0.02, OR:0.41, 95 % CI:0.18-0.92). The immunosuppression was: diabetes mellitus in 32 (44 %), alcoholism in 19 (26 %), endstage liver disease in 7 (9.5 %) and malignancy, malnutrition, pregnancy, splenectomy and immunosuppressive therapy in 15 (20.5 %). We found dissemination of infection from a contiguous site in 74 (38 %) cases, bone defects and/or CSF leakage in 36 (18.5 %) cases and hematogenous spread in 14 (7.2 %) cases. A cranial bone discontinuity and/or CSF leakage were identified in recurrent versus non-recurrent meningitis in 21 (55 %) versus 15 (10 %) episodes (p < 0.001, OR:14.41, 95 % CI:6.21-33.4). Hematogenous spread was observed only in the non-recurrent meningitis group. In recurrent versus nonrecurrent meningitis, impaired consciousness on admission was noted in 15 (40 %) versus 64 (41 %). We noted one death (2.6 %) among patients with recurrent PM group vs 42 (27 %) in the non-recurrent group (p<0.001, OR:0.07, 95 % CI:0.01-0.5). Death was associated with nonrecurrent meningitis (p < 0.001), contiguous spread (p = 0.014), immunodepression (p = 0.01) and impaired consciousness (p = 0.005). Conclusions Patients with recurrent meningitis were younger, with less immunosuppression conditions and had a better survival versus those with non-recurrent meningitis. Mortality of PM was associated with immunosuppression and impaired consciousness, but the small number of deaths in the recurrent group did not allow us to analyses the differences between the two groups.

Research paper thumbnail of Proceedings of The 8th Romanian National HIV/AIDS Congress and The 3rd Central European HIV Forum

BMC Infectious Diseases, 2016

Objectives In Bulgaria 1606 cases with HIV/AIDS were diagnosed from 1986 until 2012. Epidemiologi... more Objectives In Bulgaria 1606 cases with HIV/AIDS were diagnosed from 1986 until 2012. Epidemiological data indicated greater heterogeneity of HIV-1 positive population, including minority groups, migrants, and recent increase of men who have sex with men (MSM) and intravenous drug users (IDUs). The aim of the present study was to investigate the current molecular epidemiological picture of HIV-1 diversity among different transmission groups in Bulgaria. Materials and Methods HIV-1 diversity was analyzed in 637 (39.7 %) of all HIV/AIDS patients in the country. HIV-1 pol sequences were generated with TruGene and/or ViroSeq Genotyping Systems. The sequence alignment contained Bulgarian sequences and reference sequences from Los Alamos and GenBank. Phylogenetic relationships were inferred by ML and Bayesian analysis. Recombinations were analyzed with bootscan analysis using SimPlot software. Results The most prevalent HIV-1 strain in the studied population was found to be subtype B 38.8 %. That strain was followed by CRF01_AE 20.3 %, CRF02_AG 13.8 %, subtype C 3.6 %, subtype A1 1.6 % and the rest of strains were defined as 3 different HIV-1 subtypes (F, G and H) and 7 circulating recombinant forms (05_DF, 14_BG, 03_AB, 04_cpx, 12_BF, 33_01B and 36_cpx). In addition, 30 different unique recombinant forms consisting of 18.2 % were identified. We found that unlike in the most European countries, where subtype B is dominating, non-B HIV-1 subtypes were the most prevalent in Bulgaria. Phylogenetic analysis showed multiple clusters demonstrating rapid development of sub-epidemics in different transmission groups. In addition, unequal distribution of HIV-1 clades across different regions and transmission groups of the populations were found. Moreover, we found that various viral clades were introduced in Bulgaria from abroad by migrants. Conclusions Our analysis revealed wide HIV-1 diversity and unequal distribution of different strains among MSM, IDUs and heterosexual individuals. Phylogenetic analysis showed multiple clusters demonstrating development of local-epidemics. Significant number of HIV-1 clades were introduced from abroad by migrants. Our findings indicated that providing of detailed molecular epidemiological surveillance of HIV-1 in Bulgaria is of great importance to better understand the epidemic in the country.

Research paper thumbnail of Kaposi Sarcoma in HIV Infected Patients

Acta Medica Marisiensis, 2016

The aim of the study was to describe clinical and laboratory characteristics in HIV-infected pati... more The aim of the study was to describe clinical and laboratory characteristics in HIV-infected patients with Kaposi sarcoma (KS). Methods: We retrospectively studied data on HIV-infected patients hospitalized in one tertiary care hospital in Bucharest, Romania, in whom Kaposi Sarcoma was diagnosed, between January 2008 and November 2013. Results: We identified 27 HIV-infected patients diagnosed with KS within 6 years. They had a median age of 42 years old and a median CD4 cell count of 101 cells per mm 3 at the time of KS diagnosis. All patients received antiretroviral therapy (ART), with 18 patients (66%) already on ART at the time of KS diagnosis. Most patients (59%) were classified as ACTG poor-risk and 56% as Mitsuyasu stage I. The overall prognosis was poor, with 41% mortality, in a median time span of 6 months, significantly correlated with gastrointestinal involvement (p=0.019), poor-risk KS in ACTG classification (p<0.001) and stage IV Mitsuyasu (p=0.006). Conclusion: KS remains an important cause of morbidity and mortality in patients with HIV infection, especially in late presenters.

Research paper thumbnail of Knowledge, attitudes and practices of Romanian international travellers concerning travel-related infectious diseases and vaccinations

Research paper thumbnail of The Role of Ethnobotanical Drugs on the Recent Outbreak of Right-sided Endocarditis in Romania

Journal of gastrointestinal and liver diseases: JGLD

Background. Romania is facing a recent outbreak of infective endocarditis (IE) in injecting drug ... more Background. Romania is facing a recent outbreak of infective endocarditis (IE) in injecting drug users (IDUs). This started in 2010, after the introduction of the ethnobotanical drugs. This study explores the features of this outbreak. Methods. Retrospective study of IDU patients with IE hospitalized in the 􀀱􀁄􀁗􀁌􀁒􀁑􀁄􀁏􀀃 􀀬􀁑􀁖􀁗􀁌􀁗􀁘􀁗􀁈􀀃 􀁒􀁉􀀃 􀀬􀁑􀁉􀁈􀁆􀁗􀁌􀁒􀁘􀁖􀀃 􀀧􀁌􀁖􀁈􀁄􀁖􀁈􀁖􀀃 􀂳􀀳􀁕􀁒􀁉􀀑􀀃 􀀧􀁕􀀑􀀃 􀀰􀁄􀁗􀁈􀁌􀀃 􀀥􀁄􀁏􀃺􀂴 between 2007 and September 2012. Results. We identified 45 patients, out of which 30 were men (M/F=2), with a median age of 29 years. Thirty-seven (82%) used heroin (with a median duration of 10 years), 32 (71%) consumed ethnobotanical drugs (with a median duration of 1 year) and 24 (53%) used both drugs. Twelve cases of IE in IDUs were diagnosed in the first 9 months of 2012, 21 in 2011, 10 in 2010 and only 2 cases between 2007 and 2010. Tricuspid valve endocarditis (TVE) was diagnosed in 37 (83%) cases; the most common pathogen isolated in 31 (70%) blood cultures was Staphylococcus aureus (18 MRSA). Multip...

Research paper thumbnail of Efficacy of peginterferon alfa 2a treatment in Romanian patients with chronic hepatitis D

Research paper thumbnail of Co-infections and co-morbidities among injecting drug users versus sexually infected patients in Bucharest

Journal of the International AIDS Society, 2014

Research paper thumbnail of Initiating the antiretroviral therapy in treatment-naïve patients

BMC Infectious Diseases, 2014