Introducing ROTAVAC® to the occupied Palestinian Territories: Impact on diarrhea incidence, rotavirus prevalence and genotype composition.

BACKGROUND: Rotavirus infection remains an important cause of morbidity and mortality in children. The introduction of vaccination programs in more than 100 countries has contributed to a decrease in hospitalizations and mortality. This study investigates the epidemiological impact of the rotavirus vaccine ROTAVAC® in the Palestinian Territories, the first country to switch from ROTARIX® to this new vaccine. METHODS: Clinical surveillance data was collected fromchildren younger than 5attendingoutpatient clinics throughout Gaza withdiarrhea between 2015 and 2020. The incidence of all-cause diarrhea was assessed using an interrupted time-series approach. Rotavirus prevalence was determined at the Caritas Baby Hospital in the West Bank usingELISA on stool specimen of children younger than 5with diarrhea. Genotyping was performed on 325 randomly selected rotavirus-positive samples from January 2015 through December 2020 using multiplex PCR analysis. RESULTS: Average monthly diarrhea casesdropped by 16.7% annually fromintroduction of rotavirus vaccination in May 2016 to the beginning of the SARS-CoV-2 epidemic in March 2020 for a total of 53%. Case count declines were maintained afterthe switchto ROTAVAC® in October 2018. Rotavirus positivity in stool samples declined by 67.1% over the same period without change followingthe switch to ROTAVAC®. The distribution of predominant genotypes in rotavirus-positive stool samples changed from a pre-vaccination G1P [8] to G9P[8] and G12P[8] during the ROTARIX® period and G2P[4] after the introduction of ROTAVAC®. CONCLUSION: ROTAVAC® has shown epidemiological impact on par with ROTARIX® after its introduction to the national immunization schedule in the Palestinian Territories. A molecular genotype shift from a pre-vaccination predominance of G1P[8] to a current predominance of G2P[4] requires more long-term surveillance.

The role of time-varying viral shedding in modelling environmental surveillance for public health: revisiting the 2013 poliovirus outbreak in Israel.

Environmental pathogen surveillance is a sensitive tool that can detect early-stage outbreaks, and it is being used to track poliovirus and other pathogens. However, interpretation of longitudinal environmental surveillance signals is difficult because the relationship between infection incidence and viral load in wastewater depends on time-varying shedding intensity. We developed a mathematical model of time-varying poliovirus shedding intensity consistent with expert opinion across a range of immunization states. Incorporating this shedding model into an infectious disease transmission model, we analysed quantitative, polymerase chain reaction data from seven sites during the 2013 Israeli poliovirus outbreak. Compared to a constant shedding model, our time-varying shedding model estimated a slower peak (four weeks later), with more of the population reached by a vaccination campaign before infection and a lower cumulative incidence. We also estimated the population shed virus for an average of 29 days (95% CI 28-31), longer than expert opinion had suggested for a population that was purported to have received three or more inactivated polio vaccine (IPV) doses. One explanation is that IPV may not substantially affect shedding duration. Using realistic models of time-varying shedding coupled with longitudinal environmental surveillance may improve our understanding of outbreak dynamics of poliovirus, SARS-CoV-2, or other pathogens.

Inferring Numbers of Wild Poliovirus Excretors Using Quantitative Environmental Surveillance.

Response to and monitoring of viral outbreaks can be efficiently focused when rapid, quantitative, kinetic information provides the location and the number of infected individuals. Environmental surveillance traditionally provides information on location of populations with contagious, infected individuals since infectious poliovirus is excreted whether infections are asymptomatic or symptomatic. Here, we describe development of rapid (1 week turnaround time, TAT), quantitative RT-PCR of poliovirus RNA extracted directly from concentrated environmental surveillance samples to infer the number of infected individuals excreting poliovirus. The quantitation method was validated using data from vaccination with bivalent oral polio vaccine (bOPV). The method was then applied to infer the weekly number of excreters in a large, sustained, asymptomatic outbreak of wild type 1 poliovirus in Israel (2013) in a population where >90% of the individuals received three doses of inactivated polio vaccine (IPV). Evidence-based intervention strategies were based on the short TAT for direct quantitative detection. Furthermore, a TAT shorter than the duration of poliovirus excretion allowed resampling of infected individuals. Finally, the method documented absence of infections after successful intervention of the asymptomatic outbreak. The methodologies described here can be applied to outbreaks of other excreted viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), where there are (1) significant numbers of asymptomatic infections; (2) long incubation times during which infectious virus is excreted; and (3) limited resources, facilities, and manpower that restrict the number of individuals who can be tested and re-tested.

TP53 dysfunction in chronic lymphocytic leukemia: clinical relevance in the era of B-cell receptors and BCL-2 inhibitors.

INTRODUCTION: Patients with TP53 dysfunction, assessed by del(17p) or TP53 mutations, respond poorly to chemo-immunotherapy and fare better with the new therapies (BCR and BCL-2 inhibitors); however, it is unclear whether their response is similar to that of patients without anomalies or whether there is currently an adequate determination of TP53 dysfunction. AREA COVERED: A literature search was undertaken on clinical trials and real-world experience data on patients with TP53 dysfunction treated with different protocols. Moreover, data on the TP53 biological function and on the tests currently employed for its assessment were reviewed. EXPERT OPINION: Although TP53 dysfunction has less negative influence on the new biological therapies, patients with these alterations, particularly those with biallelic inactivation of TP53, have a worst outcome with these therapies than those without alterations. At present, a determination of TP53, particularly with next generation sequencing (NGS) methodologies, may be sufficient for the identifications of the patients unsuitable for chemo-immunotherapy, although integration with del(17p) would be advisable. For the future, more extensive determinations of the TP53 status, including functional assays, may become part of the current armamentarium for a better patient stratification and treatment with newer protocols.

Rhinovirus infections in infants suggest that early detection can prevent unnecessary treatment.

BACKGROUND: Human rhinoviruses (hRV) are small, RNA viruses of the Picornaviridae family, which are divided into three subtypes (A, B, C). hRVs are among the most common causes for acute respiratory illnesses (ARI) involving both the upper and lower respiratory tract. OBJECTIVES: This study aimed to assess the magnitude and characteristics of hRV infections in hospitalized children, aged less than 5 years, hospitalized in Israel during 2011-2012. STUDY DESIGN: The 2503 respiratory samples were subjected to real-time PCR, to detect hRV and other respiratory viruses. Rhinovirus-positive samples were further tested by sequencing to identify the infecting species. RESULTS: Of these 2503 respiratory samples, 422 tested positive for hRV, of them, 243 were from children under 5 years of age (58% of all rhinoviral-positive samples). We also found that among the ARI-associated hospital admissions, 16% were positive for rhinovirus. hRV type A was the most common species. Laboratory data showed monocytosis in 51%, hypercalcemia in 61% and lower respiratory tract involvement in 75% of patients. CONCLUSIONS: We thus recommend including rhinovirus testing as part of the routine testing performed in young children presenting with ARI.

Evaluation of Shigella Species Azithromycin CLSI Epidemiological Cutoff Values and Macrolide Resistance Genes.

Azithromycin (AZM) has been recommended by the American Academy of Pediatrics for the treatment of shigellosis in children. In this study, 502 Shigella species isolated between 2004 and 2014 were tested for AZM epidemiological cutoff values (ECV) by disk diffusion. AZM MICs and the presence of the macrolide resistance genes [erm(A), erm(B), erm(C), ere(A), ere(B), mph(A), mph(B), mph(D), mef(A), and msr(A)] were determined for all 56 (11.1%) isolates with an AZM disk diffusion zone diameter of ≤15 mm. The distribution of AZM ECV MICs was also determined for 186 Shigella isolates with a disk zone diameter of ≥16 mm. Finally, pulsed-field gel electrophoresis (PFGE) was performed on 15 Shigella flexneri isolates with an AZM disk zone diameter of <16 mm from different years and geographic locations. Serotyping the 502 Shigella species isolates revealed that 373 (74%) were S. sonnei, 119 (24%) were S. flexneri, and 10 (2%) were S. boydii Of the 119 Shigella flexneri isolates, 48 (42%) isolates had an AZM disk diffusion zone diameter of ≤15 mm and a MIC of ≥16 µg/ml. With the exception of one isolate, all were positive for the macrolide resistance gene mph(A). S. flexneri PFGE showed four distinct patterns, with patterns I and II presenting with 92.3% genetic similarity. On the other hand, 2 (0.5%) of the 373 S. sonnei isolates had the AZM non-wild-type (NWT) ECV phenotype (those with acquired or mutational resistance), as the AZM MICs were ≥32 µg/ml and the isolates were positive for the mph(A) gene. Overall, our S. flexneri results are in concordance with the CLSI AZM ECV, but isolates with an AZM disk diffusion zone diameter between 14 and 15 mm should be carefully evaluated, as the S. flexneri AZM MIC for NWT isolates may need adjustment to 32 µg/ml. Our data on S. sonnei support that the AZM NWT ECV should be 11 mm for the disk diffusion zone diameter and ≥32 µg/ml for the MICs.

Comparison of the new fully automated extraction platform eMAG to the MagNA PURE 96 and the well-established easyMAG for detection of common human respiratory viruses.

Respiratory viral infections constitute the majority of samples tested in the clinical virology laboratory during the winter season, and are mainly diagnosed using molecular assays, namely real-time PCR (qPCR). Therefore, a high-quality extraction process is critical for successful, reliable and sensitive qPCR results. Here we aimed to evaluate the performance of the newly launched eMAG compared to the fully automated MagNA PURE 96 (Roche, Germany) and to the semi-automated easyMAG (bioMerieux, France) extraction platforms. For this analysis, we assessed and compared the analytic and clinical performance of the three platforms, using 262 archived respiratory samples positive or negative to common viruses regularly examined in our laboratory (influenza A, B, H1N1pdm, Respiratory Syncytial Virus (RSV), human Metapneumovirus (hMPV), parainfluenza-3, adenovirus and negative samples). In addition, quantitated virus controls were used to determine the limit of detection of each extraction method. In all categories tested, eMAG results were comparable to those of the easyMAG and MagNa PURE 96, highly sensitive for all viruses and over 98% clinical specificity and sensitivity for all viruses tested. Together with its high level of automation, the bioMerieux eMAG is a high-quality extraction platform enabling effective molecular analysis and is mostly suitable for medium-sized laboratories.

Lenalidomide for the treatment of mantle cell lymphoma.

INTRODUCTION: Although a variety of therapeutic schemes for Mantle Cell Lymphoma (MCL) have been attempted, the clinical outcome of patients continues to be unsatisfactory especially among patients with a very high-risk profile and in the relapsed/refractory setting. For this reason, recent clinical trials have explored novel approaches, either by the use of biological agents in chemotherapy-free schedules or by integrating them with chemoimmunotherapy regimens. Areas covered: The efficacy of lenalidomide monotherapy and combination therapy established in clinical studies mainly involving relapsed/refractory MCL is reviewed. The mechanism of action of lenalidomide is also discussed. Furthermore, the current position of lenalidomide in the MCL treatment algorithm is debated. Expert opinion: Lenalidomide demonstrated high efficacy and tolerability in several clinical trials as well as in retrospective real-world reports, even in patients who relapsed or were resistant to bortezomib and ibrutinib. In 2013, lenalidomide was approved by the Food and Drug Administration (FDA) for relapsed/refractory MCL after two prior therapies including at least one prior treatment with bortezomib. However, the potential synergistic anti-neoplastic effects of lenalidomide in combination with other biological agents, i.e. ibrutinib and venetoclax, especially in the management of p53-mutated cases, still remain an open issue.

Epidemiology of the silent polio outbreak in Rahat, Israel, based on modeling of environmental surveillance data.

Israel experienced an outbreak of wild poliovirus type 1 (WPV1) in 2013-2014, detected through environmental surveillance of the sewage system. No cases of acute flaccid paralysis were reported, and the epidemic subsided after a bivalent oral polio vaccination (bOPV) campaign. As we approach global eradication, polio will increasingly be detected only through environmental surveillance. We developed a framework to convert quantitative polymerase chain reaction (qPCR) cycle threshold data into scaled WPV1 and OPV1 concentrations for inference within a deterministic, compartmental infectious disease transmission model. We used this approach to estimate the epidemic curve and transmission dynamics, as well as assess alternate vaccination scenarios. Our analysis estimates the outbreak peaked in late June, much earlier than previous estimates derived from analysis of stool samples, although the exact epidemic trajectory remains uncertain. We estimate the basic reproduction number was 1.62 (95% CI 1.04-2.02). Model estimates indicate that 59% (95% CI 9-77%) of susceptible individuals (primarily children under 10 years old) were infected with WPV1 over a little more than six months, mostly before the vaccination campaign onset, and that the vaccination campaign averted 10% (95% CI 1-24%) of WPV1 infections. As we approach global polio eradication, environmental monitoring with qPCR can be used as a highly sensitive method to enhance disease surveillance. Our analytic approach brings public health relevance to environmental data that, if systematically collected, can guide eradication efforts.

Human Coronavirus Infections in Israel: Epidemiology, Clinical Symptoms and Summer Seasonality of HCoV-HKU1.

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 2015⁻2016 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.

Characterization of human parainfluenza virus-3 circulating in Israel, 2012-2015.

BACKGROUND: Human parainfluenza virus 3 (hPIV-3) causes respiratory tract infection. OBJECTIVES: The objective of this study was to describe the epidemiology of hPIV-3 infection among hospitalized patients and characterize the circulating strains. STUDY DESIGN: A cross-sectional study was conducted using respiratory samples of 15,946 hospitalized patients with respiratory symptoms in 2012-2015 in Israel. All samples were subjected to q-PCR and q-RT-PCR to determine the presence of hPIV-3 and other respiratory viruses. Samples positive for hPIV-3 were subjected to molecular typing and phylogenetic analysis. RESULTS: Overall, 547 samples 3.4% (95% CI 3.2-3.7) were positive for hPIV-3. Of these 87 (15.9%) were mixed infections; 41.4% with adenovirus, 40.2% with RSV (40.2%) and 19.5% influenza A viruses. The prevalence of hPIV-3 was highest (5.1%) in children aged 0-4 years. Hospitalization in oncology department was associated with increased likelihood of hPIV-3 infection: adjusted odds ratio [aOR] 2.29 (95% confidence intervals [CI] 1.78-2.96), as well as hospitalization in organ transplantation department: aOR 3.65 (95% CI 2.80-4.76). The predominant lineages were C3c (62.3%) and C1b (24.6%), followed by sub-lineages C5 (8.7%) and C3b (2.9%). A new sub-lineage emerged in our analysis, named C1d, which was 17 (1.5%) nucleotide different from C1a, 25 (2.2%) nucleotide different from C1b and 24 (2.1%) nucleotide different from C1c. DISCUSSION: Young children and immunocompromised patients are likely the risk groups for severe respiratory infections with hPIV-3. Strains belonging to lineages C3c and C1b, which are present worldwide, should be targeted in vaccine development. The emergence of new lineage might have public health implications and on vaccine development.

Adenovirus respiratory tract infections in infants: a retrospective chart-review study.

BACKGROUND: Human adenoviruses have an important role in paediatric respiratory tract infections. They are estimated to cause 2-5% of the overall respiratory tract infections and 4-10% of all pneumonias. The aim of this study was to evaluate the clinical presentation and effect of adenoviral infection on the management of infected infants. METHODS: Data were collected from the medical records of patients infected with adenovirus and admitted to Caritas Baby Hospital. Adenoviral respiratory tract infections were diagnosed from nasopharyngeal aspirates using direct fluorescent antibody staining. We analysed patient clinical presentation, medical workup, laboratory workup, and antibiotic administration. This study was approved by Caritas Baby Hospital Medical Research Committee. FINDINGS: We reviewed records for 491 patients admitted to Caritas Baby Hospital with adenoviral infection between Jan 1, 2006, and June 30, 2016. Adenoviral activity was noted throughout the months of the study period, with major activity during late winter, spring, and early summer. Boys were most affected (male to female ratio 2:1). Upon admission, 187 (38%) patients were afebrile. According to the clinical presentation, 327 (67%) patients presented with upper respiratory tract infection symptoms, 165 (34%) with gastrointestinal tract symptoms, 59 (12%) with difficulty of breathing, and 46 (9%) with conjunctivitis. 279 (57%) patients had leucocytosis, whereas the C-reactive protein titre was more than 50 µg/mL in 228 (46%) patients. 92 (19%) patients needed a lumbar puncture. Overall, 354 (72%) patients received antibiotic treatment. Length of hospital stay was 1-10 days, and most patients were discharged from hospital on day 3. The average cost of hospitalisation was US$1180·5 per patient. INTERPRETATION: Adenoviral infections in infants can present with a sepsis-like picture, mandating unnecessary interventions. Clinical laboratories in hospitals must therefore have rapid and sensitive adenovirus detection techniques to assist the doctors in making appropriate treatment decisions. FUNDING: Medical Research Committee of Caritas Baby Hospital.

Forty five percent of the Israeli population were infected with the influenza B Victoria virus during the winter season 2015-16.

While infection with influenza A viruses has been extensively investigated, infections with influenza B viruses which are commonly categorized into the highly homologous Victoria and Yamagata lineages, are less studied, despite their considerable virulence. Here we used RT-PCR assays, hemagglutination inhibition assays and antibody titers to determine the levels of influenza B infection. We report of high influenza B Victoria virus prevalence in the 2015-16 winter season in Israel, affecting approximately half of the Israeli population. We further show that the Victoria B virus infected individuals of all ages and that it was present in the country throughout the entire winter season. The vaccine however included the inappropriate Yamagata virus. We propose that a quadrivalent vaccine, that includes both Yamagata and Victoria lineages, should be considered for future influenza vaccination.

Detection of Helicobacter pylori in stool samples of young children using real-time polymerase chain reaction.

BACKGROUND: The aims of this study were to develop and validate a multiplex real-time polymerase chain reaction (q-PCR) assay of Helicobacter pylori in stool samples of healthy children. Additionally, we determined the prevalence of clarithromycin resistance and cagA gene in H. pylori-positive samples. MATERIALS AND METHODS: Archived stool samples from 188 children aged 6-9 years and 272 samples of 92 infants aged 2-18 months were tested for H. pylori antigens using enzyme immunoassay (EIA). A multiplex q-PCR assay was designed to detect H. pylori 16S rRNA and urease and the human RNase P gene as an internal control. Kappa coefficient was calculated to assess the agreement between q-PCR and EIA. RESULTS: Laboratory validation of the q-PCR assay using quantitated H. pylori ATCC 43504 extracted DNA showed S-shaped amplification curves for all genes; the limit of detection was 1 CFU/reaction. No cross-reactivity with other bacterial pathogens was noted. Applying the multiplex q-PCR to DNA extracted from fecal samples showed clear amplification curves for urease gene, but not for 16S rRNA. The prevalence of H. pylori infection was 50% (95% CI 43%-57%) by q-PCR (urease cycle threshold <44) vs 59% (95% CI 52%-66%) by EIA. Kappa coefficient was .80 (P < .001) and .44 (P < .001) for children aged 6-9 years and 2-18 months, respectively. Sixteen samples were positive for cagA and three were positive for clarithromycin resistance mutation (A2143G) as confirmed by sequencing. CONCLUSIONS: The developed q-PCR can be used as a cotechnique to enhance the accuracy of H. pylori detection in epidemiological studies and in clinical settings.

Ongoing mumps outbreak in Israel, January to August 2017.

In Israel, 262 mumps cases were registered between 1 January and 28 August 2017 despite a vaccine coverage of ≥ 96%. The majority (56.5%) of cases were adolescents and young adults between 10 and 24 years of age. Nearly twice as many cases were reported in males than in females. Sequence information identified genotype G and suggested specific transmission chains in different religious communities, with the Muslim population in Jerusalem being most severely affected.

Characterization of Carbapenem-Resistant Acinetobacter baumannii Strains Isolated from Hospitalized Patients in Palestine.

The American Centers for Disease Control and Prevention (CDC) recognizes Acinetobacter baumannii as a source of global outbreaks and epidemics especially due to its increasing resistance to commercially available antibiotics. In this study, 69 single patient multidrug resistant isolates collected from all over Palestine, except Gaza, were studied. All the isolates were resistant to all the ß-lactam antibiotics including the carbapenems. Of the 69 isolates, 82.6% were positive for blaOXA-23, 14.5% were positive for blaOXA-24, and 3% were positive for blaOXA-58. None were positive for blaOXA-143 and blaOXA-235. In addition, 5.8% and 0% were positive for blaNDM and blaKPC, respectively. Of the 69 isolates, none were positive for the aminoglycoside aphA6 gene while 93% were positive for the aphA1 gene. The acetyltransferases aacC1 and aacA4 genes tested positive in 22% and 13% of the isolates, respectively. The ompA biofilm-producing virulence gene was detected in all isolates. Finally, Multilocus Sequence Typing (MLST) of 13 isolates revealed that more than one strain of A. baumannii was circulating in Palestinian hospitals as results revealed that 7 isolates were of ST208, 2 isolates ST218, 1 isolate ST231, 1 isolate ST348, and 2 new Sequence Types. The detection of these drug resistant pathogens is a reminder of the importance of active surveillance for resistant bacteria in order to prevent their spread in hospital settings.

Genetic divergence of Influenza A(H3N2) amino acid substitutions mark the beginning of the 2016-2017 winter season in Israel.

BACKGROUND: Influenza vaccine composition is reevaluated each year due to the frequency and accumulation of genetic changes that influenza viruses undergo. The beginning of the 2016-2017 influenza surveillance period in Israel has been marked by the dominance of influenza A(H3N2). OBJECTIVES: To evaluate the type, subtype, genetic evolution and amino acid substitutions of influenza A(H3N2) viruses detected among community patients with influenza-like illness (ILI) and hospitalized patients with respiratory illness in the first weeks of the 2016-2017 influenza season. STUDY DESIGN: Respiratory samples from community patients with influenza-like illness and from hospitalized patients underwent identification, subtyping and molecular characterization. Hemagglutinin sequences were compared to the vaccine strain, phylogenetic tree was created, and amino acid substitutions were determined. RESULTS: Influenza A(H3N2) predominated during the early stages of the 2016-2017 influenza season. Noticeably, approximately 20% of community patients and 36% of hospitalized patients, positive for influenza3), received the 2016-2017 influenza vaccine. The influenza A(H3N2) viruses demonstrated genetic divergence from the vaccine strain into three separate subgroups within the 3C.2a clade. One resembled the new 3C.2a1 subclade, one resembled the recently proposed 3C.2a2 subclade and the other was not previously described. Diversity was observed within each subgroup, in terms of additional amino acid substitutions. CONCLUSIONS: Characterization of the 2016-2017 A(H3N2) influenza viruses is imperative for determining the future influenza vaccine composition.

A(H1N1)pdm09 influenza infection: vaccine inefficiency.

The last influenza pandemic, caused by the swine A(H1N1)pdm09 influenza virus, began in North America at 2009. Since then, the World Health Organization (WHO) recommended integration of the swine-based virus A/California/07/2009 strain in yearly vaccinations. Yet, infections with A(H1N1)pdm09 have continued in subsequent years. The reasons for this are currently unknown. During the 2015-2016 influenza season, we noted an increased prevalence of A(H1N1)pdm09 influenza virus infection in Israel. Our phylogenetic analysis indicated that the circulating A(H1N1)pdm09 strains belonged to 6B.1 and 6B.2 clades and differed from the vaccinating strain, with approximately 18 amino acid differences found between the circulating strains and the immunizing A/California/07/2009 strain. Hemmaglutination inhibition (HI) assays demonstrated higher antibodies titer against the A/California/07/2009 vaccinating strain as compared to the circulating Israeli strains. We thus suggest that the current vaccination was not sufficiently effective and propose inclusion of the current circulating A(H1N1)pdm09 influenza viruses in the annual vaccine composition.

Influenza A(H1N1)pdm 2009 and influenza B virus co-infection in hospitalized and non-hospitalized patients during the 2015-2016 epidemic season in Israel.

BACKGROUND: Influenza A and B viruses co-infections are rare events and mainly occurred in immunocompromised patients. OBJECTIVES: In this study we report an unusually high occurrence of influenza A (H1N1)pdm 2009 and influenza B virus co-infections during the epidemic year 2015-2016. STUDY DESIGN: Nasopharyngeal swabs were collected from 1919 patients visiting 26 outpatient clinics distributed throughout Israel and presenting with influenza-like illness. In addition, hospitalized patient tested for influenza viruses were also included in the study. Patients samples collected between October 2015 and April 2016 were tested for the presence of influenza viruses by real-time PCR. RESULTS: Of the 1919 patient samples tested, 11 (0.6%) were co-infected with both influenza A(H1N1)pdm 2009 and influenza B/Victoria viruses. Similar observation was noted in four hospitalized patients during the same period. Patients at ages 1-72 years, and their clinical symptoms were similar to that of patients infected with either influenza A or B viruses. Of all patients, only one hospitalized patient was immunocompromised. IN CONCLUSION: Co-infection of influenza A(H1N1)pdm 2009 and influenza B viruses is an increasingly recognized phenomenon. This co-infection can occur not only in immunocompromised individuals, but also in immunocompetent patients. Although co-infection appears to be a rare event, it may still play a role in the epidemiology, pathogenicity and evolution of influenza viruses.