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Background Immunomodulators and anti tumor-necrosis-α antibodies (anti-TNFs) have been implicated in increased risk of Epstein–Barr virus (EBV)–driven B-cell lymphoproliferative disorders in inflammatory bowel disease (IBD) patients. However, the underlying mechanisms are poorly understood. Methods An in-vitro model of lymphoblastoid cell line (LCL) was established by co-incubation of EBV-infected human peripheral blood mononuclear cells (PBMC) with Cyclosporin-A (CSA). After 4 weeks, the resultant LCLs were analyzed by flow cytometry, telomerase activity assay, and next generation sequencing. Subsequently, LCLs were explored in the presence of therapeutic agents for IBD (anti-TNFs, vedolizumab, 6-Mercaptopurine [6MP], methotrexate). Epstein–Barr virus titers were quantitated by real-time polymerase chain reaction. Results In cultures of PBMC with EBV and CSA, LCLs were characterized as an expanded, long lived population of CD58+CD23hi B-cells with high telomerase activity and clonal expansion. Upon addition to the cell cultures, LCL percentages were higher with infliximab (median 19.21%, P = 0.011), adalimumab (median 19.85%, P = 0.003), and early washed-out 6MP (median 30.57%, P = 0.043) compared with PBMC with EBV alone (median 9.61%). However, vedolizumab had no such effect (median 8.97%; P = 0.435). Additionally, LCL expansion was accompanied by increase in intracellular, rather than extracellular, EBV viral copies. Compared with PBMC with EBV alone, high levels of LCL were subsequently observed after triple depletion of NK cells, CD4+ T cells, and CD8+ T cells (median 52.8% vs 16.4%; P = 0.046) but also in cultures depleted solely of CD4+ T cells (median 30.7%, P = 0.046). Conclusions These results suggest that both anti-TNFs and 6MP, but not vedolizumab, propagate EBV-driven lymphoblastoid transformation in an in vitro model of lymphoma. This model may prove useful for studying mechanisms underlying proneoplastic viral immune interactions of novel drugs in IBD therapy.

BackgroundMethodologically rigorous studies on Covid-19 vaccine effectiveness (VE) in preventing SARS-CoV-2 infection are critically needed to inform national and global policy on Covid-19 vaccine use. In Israel, healthcare personnel (HCP) were initially prioritized for Covid-19 vaccination, creating an ideal setting to evaluate real-world VE in a closely monitored population.MethodsWe conducted a prospective study among HCP in 6 hospitals to estimate the effectiveness of the BNT162b2 mRNA Covid-19 vaccine in preventing SARS-CoV-2 infection. Participants filled out weekly symptom questionnaires, provided weekly nasal specimens, and three serology samples – at enrollment, 30 days and 90 days. We estimated VE against PCR-confirmed SARS-CoV-2 infection using the Cox Proportional Hazards model and against a combined PCR/serology endpoint using Fisher’s exact test.FindingsOf the 1,567 HCP enrolled between December 27, 2020 and February 15, 2021, 1,250 previously uninfected participants were included in the primary analysis; 998 (79.8%) were vaccinated with their first dose prior to or at enrollment, all with Pfizer BNT162b2 mRNA vaccine. There were four PCR-positive events among vaccinated participants, and nine among unvaccinated participants. Adjusted two-dose VE against any PCR- confirmed infection was 94.5% (95% CI: 82.6%-98.2%); adjusted two-dose VE against a combined endpoint of PCR and seroconversion for a 60-day follow-up period was 94.5% (95% CI: 63.0%-99.0%). Five PCR-positive samples from study participants were sequenced; all were alpha variant.InterpretationOur prospective VE study of HCP in Israel with rigorous weekly surveillance found very high VE for two doses of Pfizer BNT162b2 mRNA vaccine against SARS-CoV-2 during a period of predominant alpha variant circulation.FundingClalit Health Services

BackgroundInvasive pneumococcal disease (IPD) declined during the COVID-19 pandemic. Previous studies hypothesized that this was due to reduced pneumococcal transmission resulting from non-pharmacological interventions. We used multiple ongoing cohort surveillance projects in children MethodsThe first SARS-CoV-2 cases were detected in February-2020, resulting in a full lockdown, followed by several partial restrictions. Data from ongoing surveillance projects captured the incidence dynamics of community-acquired alveolar pneumonia (CAAP), non-alveolar lower respiratory infections necessitating chest X-rays (NA-LRI), nasopharyngeal pneumococcal carriage in non-respiratory visits, nasopharyngeal respiratory virus detection (by PCR), and nationwide invasive pneumococcal disease (IPD). Monthly rates (January-2020 through February-2021 vs. mean monthly rates 2016-2019 [expected rates]) adjusted for age and ethnicity, were compared.FindingsCAAP and bacteremic pneumococcal pneumonia were strongly reduced (incidence rate ratios, [IRRs] 0η07 and 0η19, respectively); NA-LRI and non-pneumonia IPD were also reduced, with a lesser magnitude (IRRs, 0η46 and 0η42, respectively). In contrast, pneumococcal carriage prevalence was only slightly reduced and density of colonization and pneumococcal serotype distributions were similar to previous years. The pneumococcus-associated disease decline was temporally associated with a full suppression of RSV, influenza viruses, and hMPV, often implicated as co-pathogens with pneumococcus. In contrast, adenovirus, rhinovirus, and parainfluenza activities were within or above expected levels.InterpretationReductions in pneumococcal and pneumococcus-associated diseases occurring during the COVID-19 pandemic were not predominantly related to reduced pneumococcal transmission and carriage but were strongly associated with the complete disappearance of specific respiratory viruses.FundingPartially funded by Pfizer, Inc.

SummaryThe SARS-CoV-2 pandemic has been raging for over a year, creating global detrimental impact. The BNT162b2 mRNA vaccine has demonstrated high protection levels, yet apprehension exists that several variants of concerns (VOCs) can surmount the immune defenses generated by the vaccines. Neutralization assays have revealed some reduction in neutralization of VOCs B.1.1.7 and B.1.351, but the relevance of these assays in real life remains unclear. We performed a case-control study that examined the distribution of SARS-CoV-2 variants observed in infections of vaccinated individuals (“breakthrough cases”) and matched infections of unvaccinated individuals. We hypothesized that if there is lower vaccine effectiveness against one of the VOCs, its proportion among the breakthrough cases should be higher than among unvaccinated cases. Our results show that vaccinees that tested positive at least a week after the second dose were indeed disproportionally infected with B.1.351, as compared with unvaccinated individuals (odds ratio of 8:1). Those who tested positive between two weeks after the first dose and one week after the second dose, were disproportionally infected by B.1.1.7 (odds ratio of 26:10), suggesting reduced vaccine effectiveness against both VOCs at particular time windows following vaccination. Nevertheless, the B.1.351 incidence in Israel to-date remains low and vaccine effectiveness remains high among those fully vaccinated. These results overall suggest that vaccine breakthrough infection may be more frequent with both VOCs, yet a combination of mass-vaccination with two doses coupled with non-pharmaceutical interventions control and contain their spread.

Toward eradicating the COVID-19 pandemic, vaccines that induce high humoral and cellular immune responses are essential. However, SARS-CoV-2 variants have begun to emerge and raise concerns, as they may potentially compromise vaccine efficiency. Here, we monitored neutralization potency of convalescent or Pfizer-BTN162b2 post-vaccination sera against pseudoviruses displaying spike proteins derived from wild-type SARS-CoV-2, or its UK-B.1.1.7 and SA-B.1.351 variants. Compared to convalescent sera, vaccination induces high titers of neutralizing antibodies, which exhibit efficient neutralization potential against pseudovirus carrying wild-type SARS-CoV-2. However, while wild-type and UK-N501Y pseudoviruses were similarly neutralized, those displaying SA-N501Y/K417N/E484K spike mutations moderately resist neutralization. Contribution of single or combined spike mutations to neutralization and infectivity were monitored, highlighting mechanisms by which viral infectivity and neutralization resistance are enhanced by N501Y or E484K/K417N mutations. Our study validates the importance of the Pfizer vaccine but raises concerns regarding its efficacy against specific SARS-CoV-2 circulating variants., Graphical abstract, Kuzmina and colleagues monitored the neutralization potential of convalescent sera or sera from Pfizer-vaccinated individuals against pseudoviruses displaying wild-type, B.1.1.7, or B.1.351 SARS-CoV-2 spike proteins. While vaccine sera comparably neutralizes wild-type and B.1.1.7 pseudoviruses, the B.1.351 variant moderately resists vaccine-mediated neutralization, highlighting the importance of monitoring the emergence of variants.

Background There are limited data on influenza vaccine effectiveness (IVE) in preventing laboratory-confirmed influenza illness among healthcare personnel (HCP). Methods HCP with direct patient contact working full-time in hospitals were followed during three influenza seasons in Israel (2016–2017 to 2018–2019) and Peru (2016 to 2018). Trivalent influenza vaccines were available at all sites, except during 2018–2019 when Israel used quadrivalent vaccines; vaccination was documented by electronic medical records, vaccine registries, and/or self-report (for vaccinations outside the hospital). Twice-weekly active surveillance identified acute respiratory symptoms or febrile illness (ARFI); self-collected respiratory specimens were tested by real-time reverse transcription polymerase chain reaction (PCR) assay. IVE was 100 × 1-hazard ratio (adjusted for sex, age, occupation, and hospital). Results Among 5,489 HCP who contributed 10,041 person-seasons, influenza vaccination coverage was 47% in Israel and 32% in Peru. Of 3,056 ARFIs in Israel and 3,538 in Peru, A or B influenza virus infections were identified in 205 (7%) in Israel and 87 (2.5%) in Peru. IVE against all viruses across seasons was 1% (95% confidence interval [CI] = −30%, 25%) in Israel and 12% (95% CI = −61%, 52%) in Peru. Conclusion Estimates of IVE were null using person-time models during six study seasons in Israel and Peru.

The BNT162b2 mRNA vaccine is highly effective against SARS-CoV-2. However, apprehension exists that variants of concern (VOCs) may evade vaccine protection, due to evidence of reduced neutralization of the VOCs B.1.1.7 and B.1.351 by vaccine sera in laboratory assays. We performed a matched cohort study to examine the distribution of VOCs in infections of BNT162b2 mRNA vaccinees from Clalit Health Services (Israel) using viral genomic sequencing, and hypothesized that if vaccine effectiveness against a VOC is reduced, its proportion among breakthrough cases would be higher than in unvaccinated controls. Analyzing 813 viral genome sequences from nasopharyngeal swabs, we showed that vaccinees who tested positive at least 7 days after the second dose were disproportionally infected with B.1.351, compared with controls. Those who tested positive between 2 weeks after the first dose and 6 days after the second dose were disproportionally infected by B.1.1.7. These findings suggest reduced vaccine effectiveness against both VOCs within particular time windows. Our results emphasize the importance of rigorously tracking viral variants, and of increasing vaccination to prevent the spread of VOCs., At early time points after vaccination with a single dose or two doses of the BNT162b2 mRNA COVID-19 vaccine, breakthrough SARS-CoV-2 infections can be disproportionately caused by the B.1.1.7 or B.1.351 variants of concern, underlining the need to ensure rapid and complete vaccination.

The advent of direct-acting antivirals (DAAs) has transformed the landscape of hepatitis C virus (HCV) management. We aimed to prospectively (real-time) evaluate the feasibility of using a response-guided therapy approach, based on mathematical modeling of early viral kinetics, to reduce the duration of DAAs therapy. Patients were treated with DAAs according to the physicians’ preference. HCV was measured at baseline and at day 2 and weeks 1, 2 and 4 after treatment initiation. The primary endpoint was the proportion of patients with sustained-virological response (SVR) at 12 and/or 24 weeks post-treatment. Twenty-nine patients (mean age 54 ± 16, 44% females, 73% with HCV genotype 1), were enrolled and all completed therapy. Treatment duration was shortened in 11 of the 29 patients (38%). SVR was achieved in 28 of the 29 patients (97%). Relapse occurred post treatment in a single case of a non-cirrhotic male with genotype 3, who was treated with sofosbuvir/velpatasvir for 6 weeks. Virus sequencing did not identify baseline or treatment emergent resistance associated substitutions. Real-time mathematical modeling of early HCV kinetics can be utilized for shortening DAAs duration in approximately 40% of patients without compromising treatment efficacy.Clinical trial registration: ClinicalTrials.gov Identifier: NCT03603327.

Background An Israeli national taskforce performed a multi-center clinical and analytical validation of seven serology assays to determine their utility and limitations for SARS-CoV-2 diagnosis. Methods Serology assays from Roche, Abbott, Diasorin, BioMerieux, Beckman-Coulter, Siemens, and Mt.-Sinai ELISA were included. Negative samples from 2391 individuals representative of the Israeli population, and 698 SARS-CoV-2 PCR positive patients, collected between March and May 2020, were analyzed Findings Immunoassays sensitivities between 81.5%-89.4% and specificities between 97.7%-100% resulted in a profound impact on the expected Positive Predictive Value (PPV) in low (

Single-stage group testing uses compressed sensing for efficient high-throughput SARS-CoV-2 testing., Recent reports suggest that 10 to 30% of severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) infected patients are asymptomatic and that viral shedding may occur before symptom onset. Therefore, there is an urgent need to increase diagnostic testing capabilities to prevent disease spread. We developed P-BEST, a method for Pooling-Based Efficient SARS-CoV-2 Testing, which identifies all positive subjects within a set of samples using a single round of testing. Each sample is assigned into multiple pools using a combinatorial pooling strategy based on compressed sensing. We pooled sets of 384 samples into 48 pools, providing both an eightfold increase in testing efficiency and an eightfold reduction in test costs, while identifying up to five positive carriers. We then used P-BEST to screen 1115 health care workers using 144 tests. P- BEST provides an efficient and easy-to-implement solution for increasing testing capacity that can be easily integrated into diagnostic laboratories.

Background: The aims of this study were to evaluate the incidence of congenital cytomegalovirus (CMV) in term and near-term infants who fail hearing screen (target screening), the incidence of cong...

Adherence to treatment of chronic Hepatitis B Virus (HBV) is an important issue and can affect the complication rate. Nucleos(t)ide analogue as oral treatments are used for patients with necro-inflammatory activity and high viral load, with the goal of decline the complication rate such cirrhosis and hepatic cancer. We aimed to investigate the adherence to chronic HBV treatment. Chronic HBV patients with dispensing medication rates (DMR) of at least 80% were defined as high adherence group (HAG) and those who dispensed less than 80% as low adherence group (LAG). The study included 273 patients. 90 patients (33%) were in the LAG and 183 (67%) in the HAG. The All-cause mortality in the LAG was 15.6%, and 8.7% among the HAG (p-value = 0.09). 185 patients were of Jewish origin (mean age of 52.96 &plusmn, 14.6 years, 30% women) and 88 patients of Arab Bedouin (AB) origin (mean age of 40.86 &plusmn, 13.96 years (p-value &lt, 0.001), 42% women). The proportion of Jewish patients with high adherence was 71% (131 patients) versus 59% (52 patients) in AB patients (p-value = 0.054). The all-causes mortality was 14.6% among Jewish origin and 3.4% of AB (p-value = 0.01). We conclude that, two third of HBV carriers are with high level adherence to treatment in southern Israel, with lower but marginally significant all-cause mortality. No-significant differences in adherence patterns were noted between Arab Bedouin and Jews.

The COVID-19 pandemic is rapidly spreading throughout the world. Recent reports suggest that 10-30% of SARS-CoV-2 infected patients are asymptomatic. Other studies report that some subjects have significant viral shedding prior to symptom onset. Since both asymptomatic and pre-symptomatic subjects can spread the disease, identifying such individuals is critical for effective control of the SARS-CoV-2 pandemic. Therefore, there is an urgent need to increase diagnostic testing capabilities in order to also screen asymptomatic carriers. In fact, such tests will be routinely required until a vaccine is developed. Yet, a major bottleneck of managing the COVID-19 pandemic in many countries is diagnostic testing, due to limited laboratory capabilities as well as limited access to genome-extraction and Polymerase Chain Reaction (PCR) reagents. We developed P-BEST - a method for Pooling-Based Efficient SARS-CoV-2 Testing, using a non-adaptive group-testing approach, which significantly reduces the number of tests required to identify all positive subjects within a large set of samples. Instead of testing each sample separately, samples are pooled into groups and each pool is tested for SARS-CoV-2 using the standard clinically approved PCR-based diagnostic assay. Each sample is part of multiple pools, using a combinatorial pooling strategy based on compressed sensing designed for maximizing the ability to identify all positive individuals. We evaluated P-BEST using leftover samples that were previously clinically tested for COVID-19. In our current proof-of-concept study we pooled 384 patient samples into 48 pools providing an 8-fold increase in testing efficiency. Five sets of 384 samples, containing 1-5 positive carriers were screened and all positive carriers in each set were correctly identified. P-BEST provides an efficient and easy-to-implement solution for increasing testing capacity that will work with any clinically approved genome-extraction and PCR-based diagnostic methodologies.

Background Characteristics of hepatitis B (HBV) and delta (HDV) coinfection in various geographical regions, including Israel, remain unclear. Here we studied HDV seroprevalence in Israel, assessed HDV/HBV viral loads, circulating genotypes and hepatitis delta antigen (HDAg) conservation. Methods Serological anti HDV IgG results from 8969 HBsAg positive individuals tested in 2010-2015 were retrospectively analyzed to determine HDV seroprevalence. In a cohort of HBV/HDV coinfected (n=58) and HBV monoinfected (n=27) patients, quantitative real-time PCR (qRT-PCR) and sequencing were performed to determine viral loads, genotypes and hepatitis delta antigen (HDAg) protein sequence. Results 6.5% (587/8969) of the HBsAg positive patients were positive for anti HDV antibodies. HDV viral load was >2 log copies/ml higher than HBV viral load in most of the coinfected patients with detectable HDV RNA (86%, 50/58). HDV genotype 1 was identified in all patients, most of whom did not express HBV. While 66.6% (4/6) of the HBV/HDV co-expressing patients carried HBV-D2 only 18.5% (5/27) of the HBV monoinfections had HBV-D2 (p=0.03). Higher genetic variability in the HDAg protein sequence was associated with higher HDV viral load. Conclusions The overall significant prevalence of HDV (6.5%) mandates HDV RNA testing for all coinfected patients. Patients positive for HDV RNA (characterized by low HBV DNA blood levels) carried HDV genotype 1. Taken together, the significant HDV seroprevalence and the lack of effective anti-HDV therapy, necessitates strict clinical surveillance especially in patients with higher HDV viral loads and increased viral evolution.

In this study, we found that the measles virus (MV) can infect human-induced pluripotent stem cells (hiPSCs). Wild-type MV strains generally use human signaling lymphocyte activation molecule (SLAM; CD150) as a cellular receptor, while vaccine strains such as the Edmonston strain can use both CD150 and CD46 as receptors. It is not yet known how early in the embryonal differentiation stages these receptors are expressed. We established two hiPSCs (BGU-iPSCs and EMF-iPSCs) which express CD46 and CD150. Both cell types can be infected by MV to form persistent, noncytopathic cell lines that release infectious MV particles. Following MV persistent infection, BGU-iPSCs and EMF-iPSCs remain pluripotent and can differentiate in vitro into the three germ layers. This includes cells expressing the neuronal differentiation markers: NF68 and miRNA-124. Since the MV does not integrate into the cell's genome, it can be utilized as a vehicle to systematically introduce genes into iPSC, to dissect and to define factors regulating lineage differentiation.

Background: The advent of direct-acting antivirals (DAAs) has transformed the landscape of hepatitis C virus (HCV) management. However, the high cost of DAAs therapy has become a major barrier to HCV elimination. We aimed to prospectively evaluate the efficacy and safety of reducing the duration of DAAs therapy using response-guided therapy approach based on mathematical modeling of viral kinetics. Methods: Patients were treated with DAAs according to the physicians’ preference. HCV was measured at baseline and at day 2 and weeks 1, 2 and 4 after treatment initiation. The primary endpoint was the proportion of patients with sustained-virological response (SVR) at 12 and/or 24 weeks post-treatment. Findings: Twenty-nine patients (mean age 54±16, 44% females, 73% with HCV genotype 1), were enrolled and all completed therapy. Sofosbuvir/velpatasvir, elbasvir/grazoprevir, sofosbuvir/ledipasvir and glecaprevir/pibrentasvir, were administered in 38%, 27%, 21% and 14% of patients, respectively. Treatment duration was shortened in 11 of the 29 patients (38%). SVR was achieved in 28 of the 29 patients (97%). Relapse occurred post treatment in a single case of a non-cirrhotic male with genotype 3, who was treated with sofosbuvir/velpatasvir for 6 weeks. Virus sequencing did not identify baseline or treatment emergent resistance associated substitutions. Interpretation: Real-time modeling can be utilized for shortening DAAs duration in approximately 40% of patients without compromising treatment efficacy. Implementation of this model on a wider scale may lead to significant cost-saving and to improved access to anti-HCV care. Trial Registration: ClinicalTrials.gov Identifier: NCT03603327. Funding Statement: This research was supported in part by Clalit Health Services and the National Institutes of Health (NIH) and extramural NIH grants R01-AI078881 and R01GM121600. Declaration of Interests: OE has consulted for Gilead and Abbvie and received lecture fees from Gilead, Abbvie and MSD. HD has consulted for CoCrystal Inc. None of the other authors has any financial interest or conflict of interest related to this research. Ethics Approval Statement: The study was approved by the institutional review boards of Soroka and Rabin Medical Centers and was conducted in compliance with the Declaration of Helsinki, Good Clinical Practice guidelines, and local regulatory requirements. All patients provided written informed consent.

Human coronaviruses (HCoVs) cause mild to severe respiratory diseases. Six types of HCoVs have been discovered, the most recent one termed the Middle East respiratory syndrome coronavirus (MERS-CoV). The aim of this study is to monitor the circulation of HCoV types in the population during 2015&ndash, 2016 in Israel. HCoVs were detected by real-time PCR analysis in 1910 respiratory samples, collected from influenza-like illness (ILI) patients during the winter sentinel influenza survey across Israel. Moreover, 195 HCoV-positive samples from hospitalized patients were detected during one year at Soroka University Medical Center. While no MERS-CoV infections were detected, 10.36% of patients in the survey were infected with HCoV-OC43 (43.43%), HCoV-NL63 (44.95%), and HCoV-229E (11.62%) viruses. The HCoVs were shown to co-circulate with respiratory syncytial virus (RSV) and to appear prior to influenza virus infections. HCoV clinical symptoms were more severe than those of RSV infections but milder than influenza symptoms. Hospitalized patients had similar HCoV types percentages. However, while it was absent from the public winter survey, 22.6% of the patients were HCoV-HKU1 positives, mainly during the spring-summer period.

Background Influenza vaccine effectiveness (VE) varies by season, circulating influenza strain, age, and geographic location. There have been few studies of influenza VE among hospitalized children, particularly in Europe and the Middle East. Methods We estimated VE against influenza hospitalization among children aged 6 months to 8 years at Clalit Health Services hospitals in Israel in the 2015-2016, 2016-2017, and 2017-2018 influenza seasons, using the test-negative design. Estimates were computed for full and partial vaccination. Results We included 326 influenza-positive case patients and 2821 influenza-negative controls (140 case patients and 971 controls from 2015-2016, 36 case patients and 1069 controls from 2016-2017, and 150 case patients and 781 controls from 2017-2018). Over all seasons, VE was 53.9% for full vaccination (95% confidence interval [CI], 38.6%-68.3%), and 25.6% for partial vaccination (-3% to 47%). In 2015-2016, most viruses were influenza A(H1N1) and vaccine lineage-mismatched influenza B/Victoria; the VE for fully vaccinated children was statistically significant for influenza A (80.7%; 95% CI, 40.3%-96.1%) but not B (23.0%; -38.5% to 59.4%). During 2016-2017, influenza A(H3N2) predominated, and VE was (70.8%; 95% CI, 17.4%-92.4%). In 2017-2018, influenza A(H3N2), H1N1 and lineage-mismatched influenza B/Yamagata cocirculated; VE was statistically significant for influenza B (63.0%; 95% CI, 24.2%-83.7%) but not influenza A (46.3%; -7.2% to 75.3%). Conclusions Influenza vaccine was effective in preventing hospitalizations among fully vaccinated Israeli children over 3 influenza seasons, but not among partially vaccinated children. There was cross-lineage protection in a season where the vaccine contained B/Victoria and the circulating strain was B/Yamagata, but not in a season with the opposite vaccine-circulating strain distribution.

Background The Study of Healthcare Personnel with Influenza and other Respiratory Viruses in Israel (SHIRI) prospectively follows a cohort of healthcare personnel (HCP) in two hospitals in Israel. SHIRI will describe the frequency of influenza virus infections among HCP, identify predictors of vaccine acceptance, examine how repeated influenza vaccination may modify immunogenicity, and evaluate influenza vaccine effectiveness in preventing influenza illness and missed work. Methods Cohort enrollment began in October, 2016; a second year of the study and a second wave of cohort enrollment began in June 2017. The study will run for at least 3 years and will follow approximately 2000 HCP (who are both employees and members of Clalit Health Services [CHS]) with routine direct patient contact. Eligible HCP are recruited using a stratified sampling strategy. After informed consent, participants complete a brief enrollment survey with questions about occupational responsibilities and knowledge, attitudes, and practices about influenza vaccines. Blood samples are collected at enrollment and at the end of influenza season; HCP who choose to be vaccinated contribute additional blood one month after vaccination. During the influenza season, participants receive twice-weekly short message service (SMS) messages asking them if they have acute respiratory illness or febrile illness (ARFI) symptoms. Ill participants receive follow-up SMS messages to confirm illness symptoms and duration and are asked to self-collect a nasal swab. Information on socio-economic characteristics, current and past medical conditions, medical care utilization and vaccination history is extracted from the CHS database. Information about missed work due to illness is obtained by self-report and from employee records. Respiratory specimens from self-collected nasal swabs are tested for influenza A and B viruses, respiratory syncytial virus, human metapneumovirus, and coronaviruses using validated multiplex quantitative real-time reverse transcription polymerase chain reaction assays. The hemagglutination inhibition assay will be used to detect the presence of neutralizing influenza antibodies in serum. Discussion SHIRI will expand our knowledge of the burden of respiratory viral infections among HCP and the effectiveness of current and repeated annual influenza vaccination in preventing influenza illness, medical utilization, and missed workdays among HCP who are in direct contact with patients. Trial registration NCT03331991. Registered on November 6, 2017. Electronic supplementary material The online version of this article (10.1186/s12879-018-3444-7) contains supplementary material, which is available to authorized users.

Background Mobile phones are commonly used by healthcare workers (HCW) in the working environment, as they allow instant communication and endless resource utilisation. Studies suggest that mobile phones have been implicated as reservoirs of bacterial pathogens, with the potential to cause nosocomial infection. This study aimed to investigate the presence of Respiratory Syncytial Virus, Adenovirus and Influenza Virus on HCWs mobile phones and to identify risk factors implied by HCWs practice of mobile phones in a clinical paediatric environment. Methods Fifty HCWs' mobile phones were swabbed over both sides of the mobile phone, for testing of viral contamination during 8 days in January 2015. During the same period, a questionnaire investigating usage of mobile phones was given to 101 HCWs. Results Ten per cent of sampled phones were contaminated with viral pathogens tested for. A total of 91% of sampled individuals by questionnaire used their mobile phone within the workplace, where 37% used their phone at least every hour. Eighty-nine (88%) responders were aware that mobile phones could be a source of contamination, yet only 13 (13%) disinfect their cell phone regularly. Conclusion Mobile phones in clinical practice may be contaminated with viral pathogenic viruses. HCWs use their mobile phone regularly while working and, although the majority are aware of contamination, they do not disinfect their phones.

Viral encoded microRNAs play key roles in regulating gene expression and the life cycle of human herpes viruses. Latency is one of the hallmarks of the human cytomegalovirus (HCMV or HHV5) life cycle, and its control may have immense practical applications. The present study aims to identify HCMV encoded microRNAs during the latency phase of the virus. We used a highly sensitive real time PCR (RTPCR) assay that involves a pre-amplification step before RTPCR. It can detect HCMV encoded microRNAs (miRNAs) during latency in purified monocytes and PBMCs from HCMV IgG positive donors and in latently infected monocytic THP-1 cell lines. During the latency phase, only eight HCMV encoded microRNAs were detected in PBMCs, monocytes and in the THP-1 cells. Five originated from the UL region of the virus genome and three from the US region. Reactivation of the virus from latency, in monocytes obtained from the same donor, using dexamethasone restored the expression of all known HCMV encoded miRNAs including those that were absent during latency. We observed a shift in the abundance of the two arms of mir-US29 between the productive and latency stages of the viral life cycle, suggesting that the star "passenger" form of this microRNA is preferentially expressed during latency. As a whole, our study demonstrates that HCMV expresses during the latency phase, both in vivo and in vitro, only a subset of its microRNAs, which may indicate that they play an important role in maintenance and reactivation of latency.

Background Use of nucleic acid amplification techniques has increased the identification of respiratory viruses (RVs) in adult patients with community-acquired pneumonia (CAP). The objectives of the present study were to identify RV in patients with CAP using three different sampling methods and to compare CAP virus proportions and types with two comparison groups. Methods The study population included 183 adult patients with CAP, 450 control subjects, and 201 patients with nonpneumonic lower respiratory tract infection (NPLRTI). Each participant was sampled by oropharyngeal swab, nasopharyngeal swab, and nasopharyngeal washing, and the samples were tested for detection of 12 RVs by multiplex TaqMan Hydrolysis probe-based real-time polymerase chain reaction (Integrated DNA Technology; Coralville, IA). Results At least one RV was identified in 58 patients with CAP (31.7%) compared with 32 (7.1%) in control subjects and 104 (51.7%) in patients with NPLRTI (P < .01 and P < .01, respectively). Coronaviruses were identified in 24 (13.1%) patients with CAP, compared with 17 (3.8%) in control subjects, and 21 (10.4%) patients with NPLRTI. Respiratory syncytial virus was identified in 13 (7.1%), four (0.9%), and seven (3.5%); rhinovirus in nine (4.9%), nine (2.0%), and 15 (7.5%); and influenza virus in eight (4.4%), two (0.4%), and 63 (31.3%) patients with CAP, control subjects, and patients with NPLRTI, respectively. Conclusions The proportion of RV involvement in CAP is higher than previously reported. The proportion of RV identified in healthy subjects is significantly lower than in CAP, but it is not zero and should be weighed when interpreting corresponding proportions among patients.

Respiratory infections (RI) can be viral or bacterial in origin. In either case, the invasion of the pathogen results in production and release of various volatile organic compounds (VOCs). The present study examines the VOCs released from cultures of five viruses (influenza A, influenza B, adenovirus, respiratory syncitial virus and parainfluenza 1 virus), three bacteria (Moraxella catarrhalis, Haemophilus influenzae and Legionella pneumophila) and Mycoplasma pneumoniae isolated colonies. Our results demonstrate the involvement of inflammation-induced VOCs. Two significant VOCs were identified as associated with infectious bacterial activity, heptane and methylcyclohexane. These two VOCs have been linked in previous studies to oxidative stress effects. In order to distinguish between bacterial and viral positive cultures, we performed principal component analysis including peak identity (retention time) and VOC concentration (i.e. area under the peak) revealing 1-hexanol and 1-heptadecene to be good predictors.

We assessed the seasonality of viral lower respiratory tract infections (V-LRI), bacteremic pneumonia, nonbacteremic pneumonia and nonpneumonia invasive pneumococcal diseases (IPD) in the pre-PCV era. Both bacteremic and nonbacteremic pneumonia seasonality peaked in winter, coinciding with V-LRI seasonality, whereas non-pneumonia IPD peaked in autumn before V-LRI increase, suggesting different pathogenesis.

Many viruses can establish non-cytolytic, chronic infections in host cells. Beyond the intrinsically interesting questions of how this long-term parasitism is achieved, persistently infected cells can be useful to study virus-host interactions. MicroRNAs (miRNAs) are a class of noncoding RNAs transcribed from the genomes of all multicellular organisms and some viruses. Individual miRNAs may regulate several hundred genes. In this research we have studied the expression of a selective group of host-cell encoded miRNAs, as expressed in a Respiratory Syncytial Virus (RSV) persistently infected HEp-2 cell line (HEp-2 + RSV-GFP). The RSV is a virus that does not encode miRNAs in its genome. Our study shows that Dicer is down regulated, miRNA’s 146a-5p is strongly up-regulated and miRNAs 345-5p, let-7c-5p and miRNA’s-221 are down-regulated in HEp-2 + RSV-GFP cells. Correspondingly, changes in the miRNA 146a-5p and he sequences of the reference genes are miRNA 345-5p respective miRNAs target proteins: HSP-70 and p21, were observed. Thus, RSV persistent viral infection induces unique patterns of miRNA’s expression with relevance to how the virus regulates the host cell response to infection.

Architect (AR) and Vidas (VD) fourth generation HIV screening immunoassays, which identify early stages of HIV infections, could have false positive results especially at low signal/cutoff (S/C) AR values. Geenius HIV1/2 (GS) is a specific confirmation line immunoassay that is not highly sensitive to early HIV infections. An HIV-1 RNA assay may better detect such infections.To evaluate all AR-VD reactive samples with GS results, and to assess Xpert Qual HIV-1 RNA assay (XQ) as an alternative to GS, in the first low S/C AR-VD-reactive samples from a tested individual.First AR-VD-reactive-GS-tested results from all individuals with resolved HIV status, collected between March 2015 and March 2017 (n = 749), were retrospectively assessed. Samples with AR-VD-reactive-GS-discordant results and those with low S/C AR-VD-reactive results, were tested by XQ. Receiver operating characteristic (ROC) analysis of GS and XQ sensitivity/specificity was performed.Overall, 94.1% (705/749) of AR-VD-reactive results were true HIV-1 positive. All samples with3 S/C AR values were false positive. XQ resolved all first samples with AR-VD-reactive-GS-discordant results. The diagnostic accuracy of XQ in low (≤33 S/C) AR-VD-reactive samples was better than that of GS (97.6%, 81/83 versus 73.5%, 61/83, p 0.01). ROC analysis for low S/C AR samples was optimal for pooled XQ and GS results.Incorporating XQ in the current screening algorithm for the first AR-VD-reactive-GS-discordant samples may significantly reduce overall turn-around time of HIV-1 diagnosis.

Summary Background Early life viral infection is associated with neurogenic inflammation that is present in lymphoid tissues of the upper airway in children with obstructive sleep apnea (OSA). We hypothesized that viral genomic material is present in tonsils of children with OSA. Therefore, we examined tonsils for the presence of respiratory viruses' nucleic acids in children with OSA, and in children without OSA (undergoing surgery for recurrent throat infections (RI)). Methods Tonsillar tissue from patients with OSA and RI was subjected to multiplex quantitative real time reverse transcription PCR (mqRTPCR), analyzed for the presence of common respiratory viruses' genetic material. Results Fifty-six patients were included, of whom 34 had OSA (age (years ± S.D), 4.22 ± 1.14) and 22 with RI (4.35 ± 1.36). Respiratory viruses nucleic acids (24 detections) were observed in 17 (50%) OSA samples. In contrast, no virus was detected in RI samples (relative frequency P

Postlicensure surveillance of pneumonia incidence can be used to estimate whether pneumococcal conjugate vaccines (PCVs) affect incidence. We used Poisson regression models that control for baseline seasonality to determine the impact of PCVs and the possible effects of variations in virus activity in Israel on these surveillance estimates. PCV was associated with significant declines in radiologically confirmed alveolar pneumonia (RCAP) among patients

Background: Epstein Barr Virus (EBV) is associated with different kinds of tumors. In the present study we tried to understand its role in pediatric MDS of a 4-year-old girl with EBV infection and MDS with refractory anemia and monosomy 7. Procedures: The work-up included: hematological tests; serology for IgM, IgG antibodies to EBV; PCR for EBV; cytogenetics of bone marrow (BM), and FISH analysis of BM and blood; immunohistochemistry-LMP1 expression on BM smears. Results: Hematological follow up showed constant mild dysplastic changes mostly in the erythroid lineage. PCR for EBV showed positive results in the nasopharygeal smears as well as in blood 15 weeks after disease onset. Cytogenetic analysis showed monosomy7 inall the mitoses of BM sample. Fluorescence in situ hybridization (FISH) showed monosomy 7% in 57% of the cells, followed by a decreased tendency in the percentage of monosomy 7 cells in both BM and blood. Immunohistochemistry for EBV-latent membrane protein 1 (LMP-1) on the patient’s BM smears, 21 weeks post disease onset, showed 9% positive cells, 80% of them carried monosomy 7. Conclusion: The parallel occurrence of the EBV infection and MDS, as well as the continuous EBV PCR positive and monosomy 7, support the possibility that they are related.

Background Direct-acting antiviral (DAA) treatment regimens and response rates of patients with HCV genotype-1 (GT1) are currently considered subtype-dependent. Identification of clinically relevant resistance-associated substitutions (RASs) in the NS3 and NS5A proteins at baseline and in DAA failures, may also impact clinical decisions. Methods In a multicentre cohort study ( n=308), NS3 or NS5B sequencing ( n=248) was used to discriminate between GT1 subtypes. The correlation between baseline NS3 and NS5A RASs on the 12-week sustained virological response (SVR12) rates of 160 of the patients treated with second-generation DAAs was also assessed. Post-treatment resistance analysis was performed on samples from 58 patients exhibiting DAA virological failure. Results GT1a, GT1b and GT1d subtypes were identified in 23.0%, 75.4% and 1.2% of tested samples. GT1b was most prevalent (97.7%, 128/131) among patients born in the former Soviet Union. The Q80K NS3 RAS was identified in 17.5% (10/57) of the GT1a carriers, most of whom were Israeli-born. NS3 and NS5A baseline RASs showed a negligible correlation with SVR12 rates. Treatment-emergent RASs were observed among 8.9% (4/45) and 76.9% (10/13) of first- and second-generation DAA failures, respectively, with D168V/E (NS3), Y93H and L31M (NS5A) being the most prevalent mutations. Conclusions NS3 sequencing analysis can successfully discriminate between GT1 subtypes and identify NS3 amino acid substitutions. While pre-treatment NS3 and NS5A RASs marginally affect second-generation DAA SVR12 rates, post-treatment resistance analysis should be considered prior to re-therapy.

Background Rapid diagnosis of cutaneous leishmaniasis (CL) and identification of Leishmania species is highly important for the disease management. In Israel, CL is caused mainly by Leishmania major and Leishmania tropica species. Methods We established an easy to handle point of care lesion-swabbing, combined with a highly sensitive multiplex real time PCR (multiplex qPCR) for accurate and rapid diagnosis of Leishmania species. Results Using three probes: one general for: Leishmania species, and two specific for L major, and L tropica, we screened 1783 clinical samples collected during two years. Leishmania species was found in 1086 individuals, 1008 L major, and 70 L tropica. Eight samples positive for Leishmania species only, were further tested using a second set of multiplex qPCR developed, and were found positive for Leishmania braziliensis and Leishmania infantum/donovani (2 and 6 samples, concomitantly). Conclusions Taken together, the test enabled diagnostics and better treatment of Leishmania infections from the Old World (1078 samples) and the New World (8 samples), and the subtyping of the dominant strains in the region, as well as in returning travelers’.

Background Universal toddlers vaccination (UTV) introduced in 1999, reduced hepatitis A incidence in Israel from 50.4 to

Hepatitis C virus is a leading cause of chronic hepatitis and liver cancer. Little information exists on the interplay between innate defense mechanisms and viral antagonists that promote viral egress. Herein, the effects of Tetherin/BST-2 on HCV release were investigated. In Huh-7.5 hepatocytes, low expression levels of BST-2 were detected. Treatment of Huh-7.5 cells with IFNα, elevated BST-2 expression levels. However, HCV could not alter the expression of IFNα-induced BST-2, nor of stably over-expressed BST-2. Significantly, over expressed BST-2 moderately blocked HCV production and release from Huh-7.5 cells. Functional analysis of BST-2, confirmed its ability to inhibit the release of HIV delta-Vpu from Huh-7.5-BST-2 cells. HIV-Vpu antagonized BST-2 activity and rescued HIV delta-Vpu release from Huh-7.5-BST-2 cells. However, vpu slightly rescued HCV release and production from Huh-7.5-BST-2. We conclude that BST-2 moderately restricts HCV production and release from Huh-7.5 hepatocytes, while the virus lacks mechanisms to counteract this restriction.

MicroRNAs are key players in the regulation of gene expression by posttranscriptional suppression. They are involved in physiological processes, and thus their deregulation may contribute to the development of diseases and progression of cancer. Virus-encoded microRNAs and microRNAs of host origin play an important role in controlling the virus life cycle and immunity. The aim of this study was to determine the effect of vaccinia virus (VACV) infection on the expression of host-encoded microRNAs. A marked general suppression of most microRNAs in the infected cells was observed within 24 hours after VACV infection of a number of cell types. We demonstrate that this suppression was associated with abrogation of expression of the Dicer1 enzyme, which is a key enzyme in the generation of microRNAs.

The purpose of the present study was to characterize the microRNA transcriptome (miRNAome) of the human cytomegalovirus (HCMV or HHV5). We used deep sequencing and real time PCR (qPCR) together with bioinformatics to analyze the pattern of small RNA expression in cells infected with low-passage isolates of HCMV as well as in plasma and amniotic fluid. We report here on the discovery of four new precursors and ten new miRNAs as well as eleven microRNA-offset-RNAs (moRs) that are all encoded by HCMV. About eighty percent of the total HCMV reads were perfectly mapped to HCMV miRNAs, strongly suggestive of their important biological role that in large remains still to be defined and characterized. Taken altogether, the results of this study demonstrate the power and usefulness of the combined bioinformatics/biological approach in discovering additional important members of HCMV- encoded small RNAs and can be applied to the study of other viruses as well.

A total of 739 (225 H1N1(+)) children with a diagnosis of acute respiratory infection were hospitalized during July to December 2009. The H1N1(+) children were compared with 225 randomly enrolled H1N1(-) children with an influenza-like illness. As compared with influenza-like illness patients, patients with 2009 influenza A/H1N1 were characterized by older age, more vomiting, less hypoxemia and wheezing, lower white blood cell counts, less neutrophilia, and severe lymphopenia.

Objectives To determine the involvement of human metapneumovirus (HMPV) in childhood community-acquired alveolar pneumonia (CAAP) and compare the demographic, clinical, and laboratory features of HMPV-associated CAAP and CAAP associated with other respiratory viruses. Study design Nasopharyngeal wash specimens obtained prospectively over a 4-year period from children age

Cutaneous leishmaniasis (CL) caused by Leishmania major is common in southern Israel, while Leishmania infantum (sub-strain of L. donovani, causing zoonotic visceral leishmaniasis) infections were rarely reported in Israel and only in other regions. We report the first case of L. infantum infection in southern Israel, presented atypically as CL in an immunosuppressed 47-year old male. The patient was treated with liposomal amphotericin-B and recovered, without extra-cutaneous complications. Diagnosis of L. infantum CL was confirmed by microscopic identification of amastigotes in Gimsa-stained smear of skin lesion, positive blood serology and a positive polymerase chain reaction (PCR) amplification of the internal transcribed spacer 1 genes (ITS1) and restriction fragment length polymorphism (ITS1 PCR-RFLP). We also review the medical literature on old-world CL caused by L. infantum. Multiple L. donovani/infantum CL cases were identified in the literature search. These can be divided schematically to two: 1) In several endemic countries, L. infantum strains are the main causative agents of CL; 2) In other regions, CL is almost exclusively caused by L. major or L. tropica, while L. donovani strains CL cases were reported sporadically or as imported disease.

Background HIV in Israel started with a subtype-B epidemic among men who have sex with men, followed in the 1980s and 1990s by introductions of subtype C from Ethiopia (predominantly acquired by heterosexual transmission) and subtype A from the former Soviet Union (FSU, most often acquired by intravenous drug use). The epidemic matured over the last 15 years without additional large influx of exogenous infections. Between 2005 and 2013 the number of infected men who have sex with men (MSM) increased 2.9-fold, compared to 1.6-fold and 1.3-fold for intravenous drug users (IVDU) and Ethiopian-origin residents. Understanding contemporary spread is essential for effective public health planning. Methods We analyzed demographic and virologic data from 1,427 HIV-infected individuals diagnosed with HIV-I during 1998–2012. HIV phylogenies were reconstructed with maximum-likelihood and Bayesian methods. Results Subtype-B viruses, but not A or C, demonstrated a striking number of large clusters with common ancestors having posterior probability ≥0.95, including some suggesting presence of transmission networks. Transmitted drug resistance was highest in subtype B (13%). MSM represented a frequent risk factor in cross-ethnic transmission, demonstrated by the presence of Israeli-born with non-B virus infections and FSU immigrants with non-A subtypes. Conclusions Reconstructed phylogenetic trees demonstrated substantial grouping in subtype B, but not in non-MSM subtype-A or in subtype-C, reflecting differences in transmission dynamics linked to HIV transmission categories. Cross-ethnic spread occurred through multiple independent introductions, with MSM playing a prevalent role in the transmission of the virus. Such data provide a baseline to track epidemic trends and will be useful in informing and quantifying efforts to reduce HIV transmission.

Impregnation or coating of cotton and polyester fibers with cationic copper endows them with potent broad-spectrum antibacterial, antiviral, antifungal, and antimite properties (Borkow, G. and Gabbay, J. (2004). Putting Copper into Action: Copper-impregnated Products with Potent Biocidal Activities, FASEB Jounal, 18(14): 1728-1730). This durable platform technology enables the mass production of woven and non-woven fabrics, such as sheets, pillow covers, gowns, socks, air filters, mattress covers, carpets, etc. without the need of altering any industrial procedures or machinery, but only the introduction of copper oxide-treated fibers. The biocidal properties of fabrics containing 3-10% copper-impregnated fibers are permanent, are not affected by extreme washing conditions, and do not interfere with the manipulation of the final products (e.g., color, press, etc.). In this article, the authors describe data showing that (i) antifungal socks containing 10% w/w (weight/weight) copper-impregnated fibers alleviate athlete’s foot; (ii) antimicrobial fabrics (sheets) containing 10% (w/w) copper-impregnated fibers decrease bacterial colonization in a clinical setting; and (iii) these products do not have skin-sensitizing properties or any other adverse effects. Taken together, these results demonstrate the wide preventive and curative potential of copper oxide-impregnated apparel products.

The quest for an infectious agent that may account for cases of Hodgkin's disease (HD) especially in young adults has proven vain until lately. We have recently reported findings that suggested the presence of measles virus (MV) antigens and MV RNA in the tissues of patients with HD. Support for an association between MV and HD has been provided by recent epidemiological findings relating the occurrence of HD to exposure to measles in pregnancy and the perinatal period. We now present further evidence of this putative association based on immunohistochemical, reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ hybridisation studies (ISH) on HD tissues. Biopsies from 82 (54.3%) of our cohort of 154 patients showed a positive immunostain with at least two of the anti-measles antibodies used. Latent membrane protein-1 immunostaining for Epstein-Barr virus was positive in 46 (31.1%) of the patients examined. Reverse transcriptase-PCR and ISH for measles RNA were positive in seven and 10 of 28 patients, respectively. Preliminary clinicopathological associations between MV and HD are noted in this study, but no causal relationship can be claimed at this stage.

Epidemiologic and molecular investigations of Hodgkin's disease (HD) suggest a strong infectious association. The Epstein-Barr virus (EBV), together with its viral proteins, is expressed in Hodgkin-Reed-Sternberg (HRS) cells in the lymph nodes involved by HD. EBV is more likely to be related to childhood and older adult cases of HD and is much less frequently expressed in young adult HD patients, the group most expected to be associated with an infectious agent. In addition, the "hit and run" theory of EBV infection remains speculative and no other lymphotropic viruses studied to date seem to satisfy the quest for a new candidate virus in young adults with HD. We have recently found preliminary evidence suggesting a possible association between the measles virus (MV) and HD. This evidence is the subject of the present review.

Cutaneous leishmaniasis (CL) is an endemic zoonosis in southern Israel. In recent years, substantial urbanization has been taking place in this region. The introduction of populations into endemic foci was previously reported to facilitate human CL outbreaks. Our aim was to describe a continuous CL outbreak in southern Israel, through laboratory reports of CL diagnosis.The Soroka University Medical Center parasitology laboratory is the major laboratory confirming CL cases in our region. Data regarding patients referred to the hospital for CL diagnosis were collected retrospectively. Cases were defined by microscopic findings of skin lesion biopsies.The annual number of cases sent for CL laboratory confirmation increased from a mean of 77 ± 9 in the years 2007-2010 to 178, 327, and 528 in the years 2011, 2012, and 2013, respectively. The respective increase in annual confirmed/positive cases of CL was from 36 ± 12 to 117, 171, and 282, leading to respective increase in CL rate (per 100 000) from 5.8 ± 1.9 to 18.4, 26.3, and 42.7. The outbreak was mainly (60%) observed in the north-west area of the region.In conclusion, a sevenfold increase in laboratory-confirmed CL was observed in southern Israel in 2007-2013, probably reflecting a bigger outbreak, possibly related to urban expansion bordering with CL foci.

The magnitude and clinical significance of Hepatitis C virus (HCV) infection in dialysis patients is controversial and underestimated. This study was conducted in order to evaluate the correlation between HCV replication and antibody response to HCV in dialysis patients. HCV infection in dialysis patients was evaluated over a period of 3 years and compared to HCV infection in Liver Clinic patients. Sera were collected from 310 dialysis patients and tested for anti-HCV and HCV-RNA. In addition, HCV genotype and HCV viral load were determined in HCV-RNA-positive sera. Anti-HCV was detected in 43 (14%) of the dialysis patients. Of these, 37 (86%) were HCV-RNA-positive. Among the 267 HCV-seronegative dialysis patients, 25 (9%) were found to be HCV-RNA-positive in more than one sample during the study. These patients were characterized by low viral load; at least two orders of magnitude lower than in the group of HCV-seropositives. In contrast, in the Liver Clinic patients, HCV-RNA was found exclusively in HCV-seropositive patients. Comparison of the genotype pattern in the two groups did not reveal a difference. Our results suggest that HCV infection in dialysis units may be underestimated due to cases of low viral load, depending on the method of RNA extraction and sensitivity of the test used. Low viral load might contribute to the lack of humoral immune response seen in some dialysis patients.

The Gaza Strip borders the southern part of Israel and Egypt. There is a remarkable difference in the prevalence of antibodies to hepatitis C virus (HCV) between Israel (0.5%) and Egypt (10%). A few thousand inhabitants cross the borders daily from the Gaza Strip to both countries. The objectives of this study were to investigate the prevalence of HCV infection in the Gaza Strip, an area that was not studied before, and to study HCV transmission in the Gaza Strip by characterizing the genotypes of HCV in Southern Israel and the Gaza Strip and comparing them with those found in Egypt. HCV prevalence in the Gaza Strip was found to be 2.2%, relatively higher than in Israel but lower than in Egypt. The most common genotypes found were type 1 b in Southern Israel and type 4 in the Gaza Strip, corresponding to the most prevalent genotype in Egypt. Similarity between type 4 isolates from the Gaza Strip and Egypt was illustrated further by sequence analysis of the HCV 5' noncoding region (NCR).