Emerging SARS-CoV-2 variants may threaten global vaccination efforts and awaited reduction in out... more Emerging SARS-CoV-2 variants may threaten global vaccination efforts and awaited reduction in outbreak burden. In this study, we report a novel variant carrying the L452R mutation that emerged from a local B.1.362 lineage, B.1.362+L452R. The L452R mutation is associated with the Delta and Epsilon variants and was shown to cause increased infection and reduction in neutralization in pseudoviruses. Indeed, the B.1.362+L452R variant demonstrated a X4-fold reduction in neutralization capacity of sera from BNT162b2-vaccinated individuals compared to a wild-type strain. The variant infected 270 individuals in Israel between December 2020 and March 2021, until diminishing due to the gain in dominance of the Alpha variant in February 2021. This study demonstrates an independent, local emergence of a variant carrying a critical mutation, L452R, which may have the potential of becoming a variant of concern and emphasizes the importance of routine surveillance and detection of novel variants a...
Defining genetic diversity of viral infections directly from patient specimens is the ultimate go... more Defining genetic diversity of viral infections directly from patient specimens is the ultimate goal of surveillance. Simple tools that can provide full-length sequence information on blood borne viral hepatitis viruses: hepatitis C, hepatitis B and hepatitis D viruses (HCV, HBV and HDV) remain elusive. Here, an unbiased metagenomic next generation sequencing approach (mNGS) was used for molecular characterization of HCV infections (n = 99) from Israel which yielded full-length HCV sequences in 89% of samples, with 7 partial sequences sufficient for classification. HCV genotypes were primarily 1b (68%) and 1a (19%), with minor representation of genotypes 2c (1%) and 3a (8%). HBV/HDV coinfections were characterized by suppressed HBV viral loads, resulting in sparse mNGS coverage. A probebased enrichment approach (xGen) aiming to increase HBV and HDV coverage was validated on a panel of diverse genotypes, geography and titers. The method extended HBV genome coverage a median 61% (range 8-84%) and provided orders of magnitude boosts in reads and sequence depth for both viruses. When HBV-xGen was applied to Israeli samples, coverage was improved by 28-73% in 4 samples and identified HBV genotype A1, A2, D1 specimens and a dual B/D infection. Abundant HDV reads in mNGS libraries yielded 18/26 (69%) full genomes and 8 partial sequences, with HDV-xGen only providing minimal extension (3-11%) of what were all genotype 1 genomes. Advanced molecular approaches coupled to virus-specific capture probes promise to enhance surveillance of viral infections and aid in monitoring the spread of local subtypes.
Background: SARS-CoV-2 variant Beta (B.1.351) was designated as a Variant of Concern (VoC) after ... more Background: SARS-CoV-2 variant Beta (B.1.351) was designated as a Variant of Concern (VoC) after becoming the dominant strain in South Africa and spreading internationally. BNT162b2 showed lower levels of neutralizing antibodies against Beta than against other strains raising concerns about effectiveness of vaccines against infections caused by Beta. We estimated BNT162b2 effectiveness against Beta infections in Israel, a country with high vaccine uptake. Methods: The Ministry of Health (MoH) identified Beta cases through mandatory reporting of SARS-CoV-2 cases and whole genome sequencing (WGS) of specimens from vaccination-breakthrough infections, reinfections, arriving international travelers, and a selection of other infected persons. A cohort analysis was conducted of exposure events of contacts of primary Beta cases. WGS was conducted on available PCR-positive specimens collected from contacts. VE estimates with 95% confidence intervals (CIs) against confirmed and probable Bet...
AimCombined antiretroviral treatment (cART) traditionally consists of three antiretroviral medica... more AimCombined antiretroviral treatment (cART) traditionally consists of three antiretroviral medications, while two-drug regimens (2DR), historically used infrequently, recently been suggested to be non-inferior to three-drug regimens, is emerging as a potential treatment option and is currently a recommended option for treatment initiation in many guidelines.PurposeCharacterize the indications and clinical efficacy of 2DR use at a real-life setting in a nation-wide survey.MethodsA cross-sectional survey of Israeli patients treated by 2DR until July 2019, included demographic, immunologic, virologic, genotypic and biochemical/metabolic parameters at diagnosis, ART initiation, 2DR initiation and following 24, 48, 96 and 144 weeks of 2DR treatment.Results176 patients were included in the study. In contrast to historical data implicating ART resistance and adverse effects as the major reasons leading to 2DR switching, treatment simplification was the main reason leading to 2DR treatment ...
Introduction The zoonotic hepatitis E virus (HEV) genotype 3 (HEV-G3) has become a common cause o... more Introduction The zoonotic hepatitis E virus (HEV) genotype 3 (HEV-G3) has become a common cause of acute and chronic hepatitis among humans worldwide. In Israel, while HEV-3 sequences have previously been detected in sewage, only the non-zoonotic HEV-G1 genotype has been found in samples from human patients. Aim In this pilot study, we aimed to assess the status of HEV in a sample of the swine population and among swine farm workers in Israel. Methods Pig blood (n = 141) and faecal samples (n = 39), pig farm sewage samples (n = 8) and blood from farm workers (n = 24) were collected between February 2016 and October 2017. Anti-HEV IgG was detected using the Wantai assay. HEV RNA was analysed with the RealStar HEV kit. HEV open reading frame 1 fragments amplified from representative HEV RNA-positive samples were used for phylogenetic analysis. Results Overall prevalence of HEV antibodies in pigs was 75.9% (107/141). HEV RNA was detected in plasma (2.1%, 3/141), faecal (22.8%, 18/79) a...
0.27, 0.78). DS was significantly inversely associated with LOVS (OR 0.96; CI 0.92, 0.99) and age... more 0.27, 0.78). DS was significantly inversely associated with LOVS (OR 0.96; CI 0.92, 0.99) and age (OR 0.97; CI 0.95, 0.998), and positively associated with drug use (OR 3.96; CI 1.53, 10.23). The association between DS and LOVS was maintained after adjusting for age, gender/sexual orientation, race/ethnicity, and drug use. Conclusion. DS was highly prevalent in this cohort. The unanticipated inverse association between DS and LOVS highlights the complexity of this relationship. Despite this association, the balance of data in this cohort demonstrates an overall negative impact of DS. Further study is needed to understand this surprising finding. Disclosures. All authors: No reported disclosures.
Objectives: MSM comprise $30% of new HIV infections in Israel, a country with mixed Jewish and Ar... more Objectives: MSM comprise $30% of new HIV infections in Israel, a country with mixed Jewish and Arab populations. We molecularly characterized HIV-1 in the Arab and Jewish MSM (AMSM, JMSM) populations to reveal possible interethnical connections. Design: Cross-sectional study. Methods: All Israeli-born, HIV-1-infected MSM diagnosed between 2005 and 2016 (n ¼ 1143) were cross-matched with the National Civil Registry to identify religion (Jews/Muslims/Christians). Transmitted drug-resistance mutations (TDRM) and HIV-1 subtypes were determined on the first partial protease and reverse transcriptase sequences from treatment-naive patients and phylogenetic trees were constructed.
Study aim: to assess the incidence, risk factors and outcome of invasive pneumococcal disease (IP... more Study aim: to assess the incidence, risk factors and outcome of invasive pneumococcal disease (IPD) among the Israeli HIV population. A matched case-control study nested in a nationwide, prospective, population-based, cohort of adult IPD was performed. In addition, the HIV-IPD patients were compared to the general adult HIV population in Israel. Study period: from the introduction of PCV into the national immunization program (NIP) in July 2009 to June 2014. Each HIV patient within the IPD cohort was matched to 4 non-HIV controls. Serotyping was performed by a central laboratory using the Quellung reaction. Thirty-five IPD episodes in 33 HIV patients were identified, with a median annual incidence of 128/100,000 HIVC persons compared to 5.1/100,000 in the age-matched, non-HIV population. Compared to the general HIV population, HIV-IPD patients practiced intravenous drug use more frequently and originated from a country with generalized epidemic (OGE), mainly non-citizens lacking medical insurance. The proportion of men who have sex with men (MSM) was lower than in the general HIV population. Pneumonia was the most common clinical presentation (81%), while meningitis occurred in only one patient. Outcomes were similar to those of the IPD non-HIV population. Nineteen serotypes were identified, of which only 42% were covered by PCV13 vaccine. By 2014, none of the HIV-IPD cases belonged to serotypes covered by PCV13. In conclusion, most HIV IPD cases were from marginalized populations with poor access to health services. A decrease in IPD cases covered by PCV 13 was observed.
The American journal of tropical medicine and hygiene, Jan 6, 2016
Hepatitis E virus (HEV) is an emerging infectious agent in developed countries. HEV genotypes 1 (... more Hepatitis E virus (HEV) is an emerging infectious agent in developed countries. HEV genotypes 1 (G1) and 3 (G3) have been identified in environmental and clinical samples in Europe. In Israel, the overall prevalence of anti-HEV IgG antibodies was found to be 10.6%; however, reports of HEV infection are scarce. In this study, the presence of HEV in Israel was investigated using 169 sewage samples from 32 treatment facilities and 49 samples from acute hepatitis patients, all collected between 2013 and 2015. Fourteen sewage samples, from Haifa (11/18 samples), Tel Aviv (2/29 samples), and Beer Sheva (1/17 samples), regions with good sanitary conditions and middle-high socioeconomic populations, were HEV positive. Among the patient samples, 6.1% (3/49) were HEV positive, all returning travelers from India. Genotype analysis revealed G1 HEV in patients and G3 HEV sequences in sewage. Evidence that HEV could be establishing itself in our region may justify more active surveillance to moni...
Diagnosis of HIV infection is a multistage algorithm. Following screening with 4(th) generation c... more Diagnosis of HIV infection is a multistage algorithm. Following screening with 4(th) generation combination immunoassay, confirmation of HIV infection is performed with an antibody assay that differentiates HIV-1 from HIV-2 infection. In the newly updated algorithm, samples that are nonreactive or indeterminate in the differentiation assay are to be tested with an HIV-1 nucleic acid amplification (NAAT) test for resolution. Xpert HIV-1 Qual is a new NAAT assay approved for the identification of HIV infection in whole and dried blood. To assess the performance of Xpert HIV-1 Qual supplementary assay in resolving the clinical status of serum samples reactive by 4(th) generation immunoassays and indeterminate or negative by Geenius HIV-1/2 confirmatory assay. In a retrospective study, samples from 97 individuals for whom the true HIV-1 status was already known (by follow-up samples) and which were negative or indeterminate by HIV-1/2 Geenius assay were tested with Xpert Qual HIV-1 assay. Xpert Qual assay correctly classified all 97 samples from HIV-1 positive (n=49) and negative (n=48) individuals. The sensitivity and specificity of Xpert Qual when using the true HIV status as a reference were 100% (92.7-100% at 95% confidence interval [CI] and 92.6-100% at 95% CI, respectively). Applying Xpert Qual HIV-1 assay in the new HIV multi-stage diagnostic algorithm correctly classified 100% of HIV-1 infections including 49 from HIV-1 carriers who have not yet seroconverted. With this assay the total time required for acute HIV diagnosis could be significantly reduced.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, Jan 29, 2015
Numerous studies have shown that baseline drug resistance patterns may influence the outcome of ... more Numerous studies have shown that baseline drug resistance patterns may influence the outcome of antiretroviral therapy. Therefore guidelines recommend drug resistance testing to guide the choice of initial regimen. In addition to optimizing individual patient management, these baseline resistance data enable transmitted drug resistance (TDR) to be surveyed for public health purposes. The SPREAD-program systematically collects data to gain insight into TDR occurring in Europe since 2001. Demographic, clinical and virological data from 4,140 antiretroviral-naive HIV-infected individuals from 26 countries who were newly diagnosed between 2008 and 2010 were analyzed. Evidence of TDR was defined using the WHO list for surveillance of drug resistance mutations. Prevalence of TDR was assessed over time by comparing the results to SPREAD data from 2002-2007. Baseline susceptibility to antiretroviral drugs was predicted using Stanford HIVdb v7.0. The overall prevalence of TDR did not chan...
Bladder carcinoma is the fourth most common cancer in men and the eighth most common cancer among... more Bladder carcinoma is the fourth most common cancer in men and the eighth most common cancer among women. Our study is aimed to characterise tumour-associated antigen peptides of transitional cell carcinoma of the bladder (TCC). A DNA micro-arraybased differential display analysis of 10 000 genes was carried out, and MAGE-A8 gene expression was detected in the tumour, and not in the normal bladder. High occurrence of MAGE-A8 expression was observed in fresh tumour samples (17 out of 23) and TCC lines (four of eight). The MAGE-A8 protein sequence was screened for HLA-A2.1-binding motifs, six potential peptides were synthesised, and peptides binding to HLA-A2.1 were assured. Immunogenicity and antigenicity of the MAGE-A8 peptides were examined in the HHD system, murine class I MHC knockout mice, transgenic for HLA-A2.1. The MAGE-A8 peptide immunogenicity was examined in three modes of vaccination, delivered intranasally with cholera toxin, injected into the tail base with complete Freund's adjuvant (CFA), or presented directly as loaded onto cell surface HLA-A2.1 molecules. Two peptides, 8.1 and 8.3, induce CTL that kills the T24 TCC line in vitro, and prime human lymphocyte response of healthy donors. These results demonstrate the potential use of the MAGE-A8 peptides for specific immunotherapy of TCC.
HIV-1 RNA monitoring, both before and during antiretroviral therapy, is an integral part of HIV m... more HIV-1 RNA monitoring, both before and during antiretroviral therapy, is an integral part of HIV management worldwide. Measurements of HIV-1 viral loads are expected to assess the copy numbers of all common HIV-1 subtypes accurately and to be equally sensitive at different viral loads. In this study, we compared for the first time the performance of the NucliSens v2.0, RealTime HIV-1, Aptima HIV-1 Quant Dx, and Xpert HIV-1 viral load assays. Plasma samples ( n = 404) were selected on the basis of their NucliSens v2.0 viral load results and HIV-1 subtypes. Concordance, linear regression, and Bland-Altman plots were assessed, and mixed-model analysis was utilized to compare the analytical performance of the assays for different HIV-1 subtypes and for low and high HIV-1 copy numbers. Overall, high concordance (>83.89%), high correlation values (Pearson r values of >0.89), and good agreement were observed among all assays, although the Xpert and Aptima assays, which provided the mo...
SUMMARYDifferences in the seroprevalence and unique pattern of parvovirus B19 (B19V) acute infect... more SUMMARYDifferences in the seroprevalence and unique pattern of parvovirus B19 (B19V) acute infections have been documented around the world. This study was conducted to estimate the seroprevalence of anti-parvovirus B19V IgG antibodies in the Israeli population and to assess the pattern of acute infection based on data from two laboratories in Israel. The overall IgG prevalence in the 1008 representative sera samples was 61·4% and the age-adjusted prevalence rate was 58·2%. Seropositivity was significantly associated with age, ranging from 25·7% in children aged <10 years to 70% in people aged >20 years. While no significant differences in seropositivity were detected between sexes and population groups, significantly lower seroprevalence was observed in older Jews born in Africa or Asia. Acute infection rates of 4·1% (234 cases) were found based on the positive IgM results identified in samples from 5663 individuals collected between 2008 and 2013. Annual peaks of infection w...
Rearrangements of the human ALL-1 gene are frequently encountered in acute lymphocytic leukemias ... more Rearrangements of the human ALL-1 gene are frequently encountered in acute lymphocytic leukemias (ALL) and acute myeloid leukemias (AML). These rearrangements are mostly due to chromosome translocations and result in production of chimeric proteins composed of the N-terminal fragment of ALL-1 and the C-terminal segments of the partner proteins. The most common chromosome translocation involving ALL-1 is the t(4 : 11) associated with ALL. ALL-1 is the human homologue of Drosophila trithorax and directly activates transcription of multiple Hox genes. A preliminary DNA microarray screen indicated that the Meis1, HoxA9 and AC133 genes were overexpressed in ALLs with t(4 : 11), compared to ALLs with very similar phenotype but without the chromosomal abnormality. These genes, as well as additional five Hox genes, were subjected to comprehensive semi-quantitative or quantitative RT-PCR analysis in 57 primary ALL and AML tumors. Meis1 and HoxA9 were found expressed in 13/14 of ALLs with the...
Background: Israel has used an inactivated polio vaccine (IPV)-only schedule since 2005 (95% cove... more Background: Israel has used an inactivated polio vaccine (IPV)-only schedule since 2005 (95% coverage). Silent reintroduction of wild type poliovirus 1 (WPV1) into Israel in early 2013 was detected in Southern Israel via routine environmental surveillance without clinical cases. Objectives: To estimate the rate of WPV1 excretion by age and residence and inform decision-making regarding supplemental immunization with OPV. Study design: A convenience sample of Bedouin and Jewish residential areas in the epicenter of the incident, focusing on under 8 year-olds who not previously given OPV. Fecal samples were directly tested for WPV1 RNA using a novel qRT-PCR assay. Positive samples were confirmed by gold standard cell culture and subject to genotyping. Results: Overall, 2196 non-duplicate fecal samples were collected and analyzed. WPV1 was detected in 61 samples (2.8%), 55 of which (90.2%) were from Bedouins. WPV1 excretion rates were 5.4% among Bedouins and 0.6% among Jewish individuals. Respective age-specific rates among Bedouin and Jewish children were 4.9% and 0.2% for 0-2 years and 7.2% and 1.7% for 2-8 years. Molecular testing had 89.5% sensitivity (higher than culture) and 100% specificity. Conclusion: The rapid performance of a field study to evaluate WPV1 excretion unequivocally demonstrated substantial WPV1 infection rates among children under 8 years in Southern Israel, thus informing the decision to vaccinate this age group with bOPV and risk communication to both healthcare personnel and the public. Rapid development and implementation of molecular screening can thus underpin risk assessment and management in complex epidemiological situations.
The Israel Medical Association journal : IMAJ, 2012
Outbreaks of syphilis have been described among men who have sex with men (MSM) in many western u... more Outbreaks of syphilis have been described among men who have sex with men (MSM) in many western urban communities in the last few years. To describe the first reported outbreak of syphilis among MSM in Israel within a decade of a constant increase in human immunodeficiency virus (HIV) prevalence. All patients diagnosed with syphilis were contacted and asked about their sexual behavior, substance use and previous infections. All were tested for HIV and a phylogenetic analysis was performed. A total of 23 (59%) of all 39 male patients diagnosed with primary or secondary syphilis between August 2008 and August 2009 were interviewed. All were MSM and performed anal intercourse, while 13 (55%) reported unprotected anal intercourse. Most participants (21, 91%) practiced unprotected oral intercourse. Nine participants (39%) reported unprotected oral intercourse while using condoms during anal intercourse. Ten participants (43%) reported sexual contacts while traveling abroad in the previou...
Resistance testing is part of the routine checkup for HIV carriers in Israel and in most of the d... more Resistance testing is part of the routine checkup for HIV carriers in Israel and in most of the developed world. Viruses with mutations which confer resistance to antiretroviral therapy in treated patients and in new HIV carriers are identified. The results of these tests form the basis for updating the HIV treatment guidelines and contribute to the epidemiological and phylogenetic understanding of the HIV epidemic. The viral reverse transcriptase and protease are the targets for most of the antiretroviral drugs in use today and are included in the standard resistance testing. Recently, genotypic examination of the integrase and tropism test to verify use of the HIV CCR5 co-receptor have been introduced to better support treatment decisions and to enable effective use of all available drug combinations. New and more sensitive molecular tests, such as ultra-deep sequencing, are expected to broaden our knowledge of rare mutations not detected by the currently used methodologies. Conse...
The incidence of transitional cell carcinoma (TCC), the fourth most common neoplasm diagnosed in ... more The incidence of transitional cell carcinoma (TCC), the fourth most common neoplasm diagnosed in men, is rising. Despite the development of several noninvasive diagnostic tests, none have gained full recognition by the clinicians. Gene expression profiling of tumors can identify new molecular markers for early diagnosis and disease followup. It also allows the classification of tumors into subclasses assisting in disease diagnosis and prognosis, as well as in treatment selection. In this paper, we employed expression profiling for molecular analysis of TCC. A TCC-derived cDNA microarray was constructed and hybridized with 19 probes from normal urothelium and TCC tissues. Hierarchical clustering analysis identified all normal urothelium samples to be tightly clustered and separated from the TCC samples, with 29 of the genes significantly induced (t-test, Po10 À5) in noninvasive TCC compared to normal urothelium. The identified genes are involved in epithelial cells' functions, tumorigenesis or apoptosis, and could become molecular tools for noninvasive TCC diagnosis. Principal components analysis of the noninvasive and invasive TCC expression profiles further revealed sets of genes that are specifically induced in different tumor subsets, thus providing molecular fingerprints that expand the information gained from classical staging and grading.
Emerging SARS-CoV-2 variants may threaten global vaccination efforts and awaited reduction in out... more Emerging SARS-CoV-2 variants may threaten global vaccination efforts and awaited reduction in outbreak burden. In this study, we report a novel variant carrying the L452R mutation that emerged from a local B.1.362 lineage, B.1.362+L452R. The L452R mutation is associated with the Delta and Epsilon variants and was shown to cause increased infection and reduction in neutralization in pseudoviruses. Indeed, the B.1.362+L452R variant demonstrated a X4-fold reduction in neutralization capacity of sera from BNT162b2-vaccinated individuals compared to a wild-type strain. The variant infected 270 individuals in Israel between December 2020 and March 2021, until diminishing due to the gain in dominance of the Alpha variant in February 2021. This study demonstrates an independent, local emergence of a variant carrying a critical mutation, L452R, which may have the potential of becoming a variant of concern and emphasizes the importance of routine surveillance and detection of novel variants a...
Defining genetic diversity of viral infections directly from patient specimens is the ultimate go... more Defining genetic diversity of viral infections directly from patient specimens is the ultimate goal of surveillance. Simple tools that can provide full-length sequence information on blood borne viral hepatitis viruses: hepatitis C, hepatitis B and hepatitis D viruses (HCV, HBV and HDV) remain elusive. Here, an unbiased metagenomic next generation sequencing approach (mNGS) was used for molecular characterization of HCV infections (n = 99) from Israel which yielded full-length HCV sequences in 89% of samples, with 7 partial sequences sufficient for classification. HCV genotypes were primarily 1b (68%) and 1a (19%), with minor representation of genotypes 2c (1%) and 3a (8%). HBV/HDV coinfections were characterized by suppressed HBV viral loads, resulting in sparse mNGS coverage. A probebased enrichment approach (xGen) aiming to increase HBV and HDV coverage was validated on a panel of diverse genotypes, geography and titers. The method extended HBV genome coverage a median 61% (range 8-84%) and provided orders of magnitude boosts in reads and sequence depth for both viruses. When HBV-xGen was applied to Israeli samples, coverage was improved by 28-73% in 4 samples and identified HBV genotype A1, A2, D1 specimens and a dual B/D infection. Abundant HDV reads in mNGS libraries yielded 18/26 (69%) full genomes and 8 partial sequences, with HDV-xGen only providing minimal extension (3-11%) of what were all genotype 1 genomes. Advanced molecular approaches coupled to virus-specific capture probes promise to enhance surveillance of viral infections and aid in monitoring the spread of local subtypes.
Background: SARS-CoV-2 variant Beta (B.1.351) was designated as a Variant of Concern (VoC) after ... more Background: SARS-CoV-2 variant Beta (B.1.351) was designated as a Variant of Concern (VoC) after becoming the dominant strain in South Africa and spreading internationally. BNT162b2 showed lower levels of neutralizing antibodies against Beta than against other strains raising concerns about effectiveness of vaccines against infections caused by Beta. We estimated BNT162b2 effectiveness against Beta infections in Israel, a country with high vaccine uptake. Methods: The Ministry of Health (MoH) identified Beta cases through mandatory reporting of SARS-CoV-2 cases and whole genome sequencing (WGS) of specimens from vaccination-breakthrough infections, reinfections, arriving international travelers, and a selection of other infected persons. A cohort analysis was conducted of exposure events of contacts of primary Beta cases. WGS was conducted on available PCR-positive specimens collected from contacts. VE estimates with 95% confidence intervals (CIs) against confirmed and probable Bet...
AimCombined antiretroviral treatment (cART) traditionally consists of three antiretroviral medica... more AimCombined antiretroviral treatment (cART) traditionally consists of three antiretroviral medications, while two-drug regimens (2DR), historically used infrequently, recently been suggested to be non-inferior to three-drug regimens, is emerging as a potential treatment option and is currently a recommended option for treatment initiation in many guidelines.PurposeCharacterize the indications and clinical efficacy of 2DR use at a real-life setting in a nation-wide survey.MethodsA cross-sectional survey of Israeli patients treated by 2DR until July 2019, included demographic, immunologic, virologic, genotypic and biochemical/metabolic parameters at diagnosis, ART initiation, 2DR initiation and following 24, 48, 96 and 144 weeks of 2DR treatment.Results176 patients were included in the study. In contrast to historical data implicating ART resistance and adverse effects as the major reasons leading to 2DR switching, treatment simplification was the main reason leading to 2DR treatment ...
Introduction The zoonotic hepatitis E virus (HEV) genotype 3 (HEV-G3) has become a common cause o... more Introduction The zoonotic hepatitis E virus (HEV) genotype 3 (HEV-G3) has become a common cause of acute and chronic hepatitis among humans worldwide. In Israel, while HEV-3 sequences have previously been detected in sewage, only the non-zoonotic HEV-G1 genotype has been found in samples from human patients. Aim In this pilot study, we aimed to assess the status of HEV in a sample of the swine population and among swine farm workers in Israel. Methods Pig blood (n = 141) and faecal samples (n = 39), pig farm sewage samples (n = 8) and blood from farm workers (n = 24) were collected between February 2016 and October 2017. Anti-HEV IgG was detected using the Wantai assay. HEV RNA was analysed with the RealStar HEV kit. HEV open reading frame 1 fragments amplified from representative HEV RNA-positive samples were used for phylogenetic analysis. Results Overall prevalence of HEV antibodies in pigs was 75.9% (107/141). HEV RNA was detected in plasma (2.1%, 3/141), faecal (22.8%, 18/79) a...
0.27, 0.78). DS was significantly inversely associated with LOVS (OR 0.96; CI 0.92, 0.99) and age... more 0.27, 0.78). DS was significantly inversely associated with LOVS (OR 0.96; CI 0.92, 0.99) and age (OR 0.97; CI 0.95, 0.998), and positively associated with drug use (OR 3.96; CI 1.53, 10.23). The association between DS and LOVS was maintained after adjusting for age, gender/sexual orientation, race/ethnicity, and drug use. Conclusion. DS was highly prevalent in this cohort. The unanticipated inverse association between DS and LOVS highlights the complexity of this relationship. Despite this association, the balance of data in this cohort demonstrates an overall negative impact of DS. Further study is needed to understand this surprising finding. Disclosures. All authors: No reported disclosures.
Objectives: MSM comprise $30% of new HIV infections in Israel, a country with mixed Jewish and Ar... more Objectives: MSM comprise $30% of new HIV infections in Israel, a country with mixed Jewish and Arab populations. We molecularly characterized HIV-1 in the Arab and Jewish MSM (AMSM, JMSM) populations to reveal possible interethnical connections. Design: Cross-sectional study. Methods: All Israeli-born, HIV-1-infected MSM diagnosed between 2005 and 2016 (n ¼ 1143) were cross-matched with the National Civil Registry to identify religion (Jews/Muslims/Christians). Transmitted drug-resistance mutations (TDRM) and HIV-1 subtypes were determined on the first partial protease and reverse transcriptase sequences from treatment-naive patients and phylogenetic trees were constructed.
Study aim: to assess the incidence, risk factors and outcome of invasive pneumococcal disease (IP... more Study aim: to assess the incidence, risk factors and outcome of invasive pneumococcal disease (IPD) among the Israeli HIV population. A matched case-control study nested in a nationwide, prospective, population-based, cohort of adult IPD was performed. In addition, the HIV-IPD patients were compared to the general adult HIV population in Israel. Study period: from the introduction of PCV into the national immunization program (NIP) in July 2009 to June 2014. Each HIV patient within the IPD cohort was matched to 4 non-HIV controls. Serotyping was performed by a central laboratory using the Quellung reaction. Thirty-five IPD episodes in 33 HIV patients were identified, with a median annual incidence of 128/100,000 HIVC persons compared to 5.1/100,000 in the age-matched, non-HIV population. Compared to the general HIV population, HIV-IPD patients practiced intravenous drug use more frequently and originated from a country with generalized epidemic (OGE), mainly non-citizens lacking medical insurance. The proportion of men who have sex with men (MSM) was lower than in the general HIV population. Pneumonia was the most common clinical presentation (81%), while meningitis occurred in only one patient. Outcomes were similar to those of the IPD non-HIV population. Nineteen serotypes were identified, of which only 42% were covered by PCV13 vaccine. By 2014, none of the HIV-IPD cases belonged to serotypes covered by PCV13. In conclusion, most HIV IPD cases were from marginalized populations with poor access to health services. A decrease in IPD cases covered by PCV 13 was observed.
The American journal of tropical medicine and hygiene, Jan 6, 2016
Hepatitis E virus (HEV) is an emerging infectious agent in developed countries. HEV genotypes 1 (... more Hepatitis E virus (HEV) is an emerging infectious agent in developed countries. HEV genotypes 1 (G1) and 3 (G3) have been identified in environmental and clinical samples in Europe. In Israel, the overall prevalence of anti-HEV IgG antibodies was found to be 10.6%; however, reports of HEV infection are scarce. In this study, the presence of HEV in Israel was investigated using 169 sewage samples from 32 treatment facilities and 49 samples from acute hepatitis patients, all collected between 2013 and 2015. Fourteen sewage samples, from Haifa (11/18 samples), Tel Aviv (2/29 samples), and Beer Sheva (1/17 samples), regions with good sanitary conditions and middle-high socioeconomic populations, were HEV positive. Among the patient samples, 6.1% (3/49) were HEV positive, all returning travelers from India. Genotype analysis revealed G1 HEV in patients and G3 HEV sequences in sewage. Evidence that HEV could be establishing itself in our region may justify more active surveillance to moni...
Diagnosis of HIV infection is a multistage algorithm. Following screening with 4(th) generation c... more Diagnosis of HIV infection is a multistage algorithm. Following screening with 4(th) generation combination immunoassay, confirmation of HIV infection is performed with an antibody assay that differentiates HIV-1 from HIV-2 infection. In the newly updated algorithm, samples that are nonreactive or indeterminate in the differentiation assay are to be tested with an HIV-1 nucleic acid amplification (NAAT) test for resolution. Xpert HIV-1 Qual is a new NAAT assay approved for the identification of HIV infection in whole and dried blood. To assess the performance of Xpert HIV-1 Qual supplementary assay in resolving the clinical status of serum samples reactive by 4(th) generation immunoassays and indeterminate or negative by Geenius HIV-1/2 confirmatory assay. In a retrospective study, samples from 97 individuals for whom the true HIV-1 status was already known (by follow-up samples) and which were negative or indeterminate by HIV-1/2 Geenius assay were tested with Xpert Qual HIV-1 assay. Xpert Qual assay correctly classified all 97 samples from HIV-1 positive (n=49) and negative (n=48) individuals. The sensitivity and specificity of Xpert Qual when using the true HIV status as a reference were 100% (92.7-100% at 95% confidence interval [CI] and 92.6-100% at 95% CI, respectively). Applying Xpert Qual HIV-1 assay in the new HIV multi-stage diagnostic algorithm correctly classified 100% of HIV-1 infections including 49 from HIV-1 carriers who have not yet seroconverted. With this assay the total time required for acute HIV diagnosis could be significantly reduced.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, Jan 29, 2015
Numerous studies have shown that baseline drug resistance patterns may influence the outcome of ... more Numerous studies have shown that baseline drug resistance patterns may influence the outcome of antiretroviral therapy. Therefore guidelines recommend drug resistance testing to guide the choice of initial regimen. In addition to optimizing individual patient management, these baseline resistance data enable transmitted drug resistance (TDR) to be surveyed for public health purposes. The SPREAD-program systematically collects data to gain insight into TDR occurring in Europe since 2001. Demographic, clinical and virological data from 4,140 antiretroviral-naive HIV-infected individuals from 26 countries who were newly diagnosed between 2008 and 2010 were analyzed. Evidence of TDR was defined using the WHO list for surveillance of drug resistance mutations. Prevalence of TDR was assessed over time by comparing the results to SPREAD data from 2002-2007. Baseline susceptibility to antiretroviral drugs was predicted using Stanford HIVdb v7.0. The overall prevalence of TDR did not chan...
Bladder carcinoma is the fourth most common cancer in men and the eighth most common cancer among... more Bladder carcinoma is the fourth most common cancer in men and the eighth most common cancer among women. Our study is aimed to characterise tumour-associated antigen peptides of transitional cell carcinoma of the bladder (TCC). A DNA micro-arraybased differential display analysis of 10 000 genes was carried out, and MAGE-A8 gene expression was detected in the tumour, and not in the normal bladder. High occurrence of MAGE-A8 expression was observed in fresh tumour samples (17 out of 23) and TCC lines (four of eight). The MAGE-A8 protein sequence was screened for HLA-A2.1-binding motifs, six potential peptides were synthesised, and peptides binding to HLA-A2.1 were assured. Immunogenicity and antigenicity of the MAGE-A8 peptides were examined in the HHD system, murine class I MHC knockout mice, transgenic for HLA-A2.1. The MAGE-A8 peptide immunogenicity was examined in three modes of vaccination, delivered intranasally with cholera toxin, injected into the tail base with complete Freund's adjuvant (CFA), or presented directly as loaded onto cell surface HLA-A2.1 molecules. Two peptides, 8.1 and 8.3, induce CTL that kills the T24 TCC line in vitro, and prime human lymphocyte response of healthy donors. These results demonstrate the potential use of the MAGE-A8 peptides for specific immunotherapy of TCC.
HIV-1 RNA monitoring, both before and during antiretroviral therapy, is an integral part of HIV m... more HIV-1 RNA monitoring, both before and during antiretroviral therapy, is an integral part of HIV management worldwide. Measurements of HIV-1 viral loads are expected to assess the copy numbers of all common HIV-1 subtypes accurately and to be equally sensitive at different viral loads. In this study, we compared for the first time the performance of the NucliSens v2.0, RealTime HIV-1, Aptima HIV-1 Quant Dx, and Xpert HIV-1 viral load assays. Plasma samples ( n = 404) were selected on the basis of their NucliSens v2.0 viral load results and HIV-1 subtypes. Concordance, linear regression, and Bland-Altman plots were assessed, and mixed-model analysis was utilized to compare the analytical performance of the assays for different HIV-1 subtypes and for low and high HIV-1 copy numbers. Overall, high concordance (>83.89%), high correlation values (Pearson r values of >0.89), and good agreement were observed among all assays, although the Xpert and Aptima assays, which provided the mo...
SUMMARYDifferences in the seroprevalence and unique pattern of parvovirus B19 (B19V) acute infect... more SUMMARYDifferences in the seroprevalence and unique pattern of parvovirus B19 (B19V) acute infections have been documented around the world. This study was conducted to estimate the seroprevalence of anti-parvovirus B19V IgG antibodies in the Israeli population and to assess the pattern of acute infection based on data from two laboratories in Israel. The overall IgG prevalence in the 1008 representative sera samples was 61·4% and the age-adjusted prevalence rate was 58·2%. Seropositivity was significantly associated with age, ranging from 25·7% in children aged <10 years to 70% in people aged >20 years. While no significant differences in seropositivity were detected between sexes and population groups, significantly lower seroprevalence was observed in older Jews born in Africa or Asia. Acute infection rates of 4·1% (234 cases) were found based on the positive IgM results identified in samples from 5663 individuals collected between 2008 and 2013. Annual peaks of infection w...
Rearrangements of the human ALL-1 gene are frequently encountered in acute lymphocytic leukemias ... more Rearrangements of the human ALL-1 gene are frequently encountered in acute lymphocytic leukemias (ALL) and acute myeloid leukemias (AML). These rearrangements are mostly due to chromosome translocations and result in production of chimeric proteins composed of the N-terminal fragment of ALL-1 and the C-terminal segments of the partner proteins. The most common chromosome translocation involving ALL-1 is the t(4 : 11) associated with ALL. ALL-1 is the human homologue of Drosophila trithorax and directly activates transcription of multiple Hox genes. A preliminary DNA microarray screen indicated that the Meis1, HoxA9 and AC133 genes were overexpressed in ALLs with t(4 : 11), compared to ALLs with very similar phenotype but without the chromosomal abnormality. These genes, as well as additional five Hox genes, were subjected to comprehensive semi-quantitative or quantitative RT-PCR analysis in 57 primary ALL and AML tumors. Meis1 and HoxA9 were found expressed in 13/14 of ALLs with the...
Background: Israel has used an inactivated polio vaccine (IPV)-only schedule since 2005 (95% cove... more Background: Israel has used an inactivated polio vaccine (IPV)-only schedule since 2005 (95% coverage). Silent reintroduction of wild type poliovirus 1 (WPV1) into Israel in early 2013 was detected in Southern Israel via routine environmental surveillance without clinical cases. Objectives: To estimate the rate of WPV1 excretion by age and residence and inform decision-making regarding supplemental immunization with OPV. Study design: A convenience sample of Bedouin and Jewish residential areas in the epicenter of the incident, focusing on under 8 year-olds who not previously given OPV. Fecal samples were directly tested for WPV1 RNA using a novel qRT-PCR assay. Positive samples were confirmed by gold standard cell culture and subject to genotyping. Results: Overall, 2196 non-duplicate fecal samples were collected and analyzed. WPV1 was detected in 61 samples (2.8%), 55 of which (90.2%) were from Bedouins. WPV1 excretion rates were 5.4% among Bedouins and 0.6% among Jewish individuals. Respective age-specific rates among Bedouin and Jewish children were 4.9% and 0.2% for 0-2 years and 7.2% and 1.7% for 2-8 years. Molecular testing had 89.5% sensitivity (higher than culture) and 100% specificity. Conclusion: The rapid performance of a field study to evaluate WPV1 excretion unequivocally demonstrated substantial WPV1 infection rates among children under 8 years in Southern Israel, thus informing the decision to vaccinate this age group with bOPV and risk communication to both healthcare personnel and the public. Rapid development and implementation of molecular screening can thus underpin risk assessment and management in complex epidemiological situations.
The Israel Medical Association journal : IMAJ, 2012
Outbreaks of syphilis have been described among men who have sex with men (MSM) in many western u... more Outbreaks of syphilis have been described among men who have sex with men (MSM) in many western urban communities in the last few years. To describe the first reported outbreak of syphilis among MSM in Israel within a decade of a constant increase in human immunodeficiency virus (HIV) prevalence. All patients diagnosed with syphilis were contacted and asked about their sexual behavior, substance use and previous infections. All were tested for HIV and a phylogenetic analysis was performed. A total of 23 (59%) of all 39 male patients diagnosed with primary or secondary syphilis between August 2008 and August 2009 were interviewed. All were MSM and performed anal intercourse, while 13 (55%) reported unprotected anal intercourse. Most participants (21, 91%) practiced unprotected oral intercourse. Nine participants (39%) reported unprotected oral intercourse while using condoms during anal intercourse. Ten participants (43%) reported sexual contacts while traveling abroad in the previou...
Resistance testing is part of the routine checkup for HIV carriers in Israel and in most of the d... more Resistance testing is part of the routine checkup for HIV carriers in Israel and in most of the developed world. Viruses with mutations which confer resistance to antiretroviral therapy in treated patients and in new HIV carriers are identified. The results of these tests form the basis for updating the HIV treatment guidelines and contribute to the epidemiological and phylogenetic understanding of the HIV epidemic. The viral reverse transcriptase and protease are the targets for most of the antiretroviral drugs in use today and are included in the standard resistance testing. Recently, genotypic examination of the integrase and tropism test to verify use of the HIV CCR5 co-receptor have been introduced to better support treatment decisions and to enable effective use of all available drug combinations. New and more sensitive molecular tests, such as ultra-deep sequencing, are expected to broaden our knowledge of rare mutations not detected by the currently used methodologies. Conse...
The incidence of transitional cell carcinoma (TCC), the fourth most common neoplasm diagnosed in ... more The incidence of transitional cell carcinoma (TCC), the fourth most common neoplasm diagnosed in men, is rising. Despite the development of several noninvasive diagnostic tests, none have gained full recognition by the clinicians. Gene expression profiling of tumors can identify new molecular markers for early diagnosis and disease followup. It also allows the classification of tumors into subclasses assisting in disease diagnosis and prognosis, as well as in treatment selection. In this paper, we employed expression profiling for molecular analysis of TCC. A TCC-derived cDNA microarray was constructed and hybridized with 19 probes from normal urothelium and TCC tissues. Hierarchical clustering analysis identified all normal urothelium samples to be tightly clustered and separated from the TCC samples, with 29 of the genes significantly induced (t-test, Po10 À5) in noninvasive TCC compared to normal urothelium. The identified genes are involved in epithelial cells' functions, tumorigenesis or apoptosis, and could become molecular tools for noninvasive TCC diagnosis. Principal components analysis of the noninvasive and invasive TCC expression profiles further revealed sets of genes that are specifically induced in different tumor subsets, thus providing molecular fingerprints that expand the information gained from classical staging and grading.
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Papers by Orna Mor