Adenovirus Respiratory Infection among Immunocompetent Patients in a Pediatric Intensive Care Unit During 10-year period: Co-morbidity is common.

BACKGROUND: Adenovirus is responsible for 2-7% of childhood viral respiratory infections, 5-11% of viral pneumonia and bronchiolitis. Most are self-limited but may cause severe respiratory infection. OBJECTIVES: To describe adenovirus respiratory infection in immunocompetent children in a pediatric intensive care unit (PICU). METHODS: Children with adenovirus respiratory infection in our PICU from 2007 to 2016 were included. Data were retrospectively retrieved, including background, clinical manifestation, and treatment. Adenovirus was diagnosed by polymerase chain reaction, immune fluorescence, or both. RESULTS: Of 9397 samples, 956 were positive for adenovirus in children hospitalized during the study period. In total, 49 patients (aged 2 months-11.5 years) were admitted to our PICU, five were immunocompromised and excluded from the study, 19/44 (43%) were referred from other hospitals. Twenty-eight (64%) had underlying conditions, 66% had fever and cough, 11% had conjunctivitis, and 34% received antibiotics before admission. White blood cell counts ranged from 790 to 34,300 (mean 14,600) and 36% had counts above 15,000. Chest X-ray was consistent with viral infection in 77% of patients and normal in three (13.6%). Viral co-infection was found in 9 patients, 7 had presumed bacterial super-infection, and 27 (61.4%) needed mechanical ventilation. Two patients received cidofovir, 33 (75%) steroids, and 37 (84 %) antibiotics. Four patients died. CONCLUSIONS: Adenovirus respiratory infection may cause severe disease necessitating PICU admission and mechanical ventilation, mostly in patients with underlying conditions. Many patients received steroids and antibiotics, which may be unnecessary. Mortality was 9%, mainly among young infants and those with underlying conditions.

Evidence for Hepatitis A virus endemic circulation in Israel despite universal toddlers' vaccination since 1999 and low clinical incidence in all age groups.

Background: Universal toddlers vaccination (UTV) introduced in 1999, reduced hepatitis A incidence in Israel from 50.4 to <1.0/100,000. The current Hepatitis A virus (HAV) molecular epidemiology in Israel was studied 13-14y post UTV introduction.. Methods: An outbreak in Tel-Aviv with 75 cases in 2012-2013 was investigated. Real-time RT-PCR and sequencing of the VP1-2A region (1100bp) was done on: a. serum samples from patients with acute Hepatitis A (12/ 75 in Tel-Aviv and 31 patients hospitalized in 3 other major cities in 2011-2013); b. in sewage samples (27 from metropolitan Tel-Aviv, 14 from the other 3 cities and 6 from Gaza). Results: The outbreak began among intravenous drug users then spread to the general population. Patients' mean age was 33.2y, 4/75(5.3%) had been vaccinated and 58/75(77.3%) were hospitalized. No common environmental source was found. HAV was detected in sewage samples: 16/27(59.2%) from Tel-Aviv; 4/14(28.6%) collected throughout Israel and 6/6 (100%) from Gaza. Genotype IB predominated (52/53 sequenced samples) and identical strains were demonstrated in the Israeli and Palestinian populations by phylogenetic analysis. Conclusions: Despite the UTV success, HAV circulation in the Israeli population continues, apparently due to its close contacts with the endemic Palestinian population. Reassessment of vaccination policy is recommended.

[THE MORBIDITY AND MORTALITY OF INFLUENZA PATIENTS TREATED AT RAMBAM MEDICAL CENTER INTENSIVE CARE UNIT IN THE YEARS 2009-2014].

INTRODUCTION: Data regarding the characteristics and results of the treatment of patients hospitalized in intensive care units (ICUs) with influenza in Israel are limited. AIMS: We evaluated the characteristics and outcomes of patients treated at Rambam Medical Center at the adult department of critical care medicine for influenza between the years 2009-2014. METHODS: A retrospective cohort study was conducted. Patients were detected by laboratory reports and data were extracted from electronic medical records. RESULTS: The study included 64 patients with laboratory-proven influenza. Median age was 54 years (range 17-83) and symptom duration before admission was 5 days (1-14). The median APACHE-II score at admission was 31.5 and 63.5% were in hemodynamic shock mandating the use of vasopressors. All patients received mechanical ventilation. Inhalation of nitric oxide was needed in a third; 14.3% needed Intra-Pulmonary Percussive Ventilation and steroids were given to 57.1%. ICU mortality was 24/64 (37.5%). Factors significantly associated with mortality were older age, longer length of disease prior to ICU admission, APACHE-II score, septic shock and creatinine. Mortality during the last season was lower than observed during the 2009 pandemia despite increasing severity of illness. CONCLUSIONS: The appearance of a new strain of influenza leads to high morbidity, complications and mortality due to low population immunity. There are no randomized controlled trials evaluating the efficacy of anti-viral drugs and other treatments in severe Influenza with complications. DISCUSSION: The treatment of critically-ill patients with severe influenza is complex, mandates advanced techniques of mechanical ventilation and hemodynamic support. Under intense supportive care most patients with influenza survive.

Comparative Characteristics of the 2009 Pandemic Influenza A (H1N1) Virus and 2010-2011 Seasonal Influenza in Pediatric Patients.

BACKGROUND: In March 2009 the pandemic influenza A (H1N1) strain was identified. The disease initially appeared to be accompanied by complications and high mortality rates. It became an endemic virus during the influenza season in our region, along with the classical seasonal H3N2. OBJECTIVES: To identify the burden of pandemic influenza, its effect in pediatric patients, and complicated hospitalizations, compared to seasonal influenza years after the pandemic. METHODS: A retrospective observational study was conducted at a tertiary hospital. Data were collected from the medical records of all children who were hospitalized from April 2009 to 2011 with laboratory-confirmed influenza. RESULTS: Of 191 patients with influenza, 100 had the 2009 pandemic influenza, 62 had seasonal influenza, and 29 had H1N1 in 2010-2011. Patients with the 2009 H1N1 were characterized by older age, more co-morbidity conditions and more symptoms including fever, cough and rhinitis on admission. No significant differences in outcomes between the groups were recorded. Of patients hospitalized with pandemic influenza in 2009, 28% had complicated hospitalizations, compared with 17.7% of patients hospitalized with seasonal influenza in 2010-11. Children with pandemic influenza received more oseltamivir (Tamiflu®) (94% vs. 19.4%, P < 0.001) and more antibiotics than the other groups. CONCLUSIONS: The type of influenza had no effect on outcome. There were no significant differences between groups in the percentages of in-hospital mortality, admission to intensive care units, prolonged hospitalization (> 9 days), or the development of complications during hospitalization.

Human Herpes Virus-6 Following Pediatric Allogeneic Hematopoietic Stem Cell Transplantation.

BACKGROUND: Human herpes virus-6 (HHV-6) reactivation after hematopoietic stem cell transplantation (HSCT) is well known and has been linked with several clinical manifestations. The significance of HHV-6 viremia and related complications in this setting is still unclear. OBJECTIVE: To estimate the incidence of HHV-6 reactivation and associated morbidity in children undergoing allogeneic HSCT. METHODS: Blood samples obtained weekly (for cytomegalovirus surveillance) from children who underwent allogeneic HCST during the period January 2006-June 2010 were retrospectively tested for the presence of HHV-6 DNA using standard real-time polymerase chain reaction (PCR) assay. Clinical records were reviewed for correlation between viremia and clinical manifestations. RESULTS: Samples from 39 children were tested. Twenty patients had viral loads above 1000 copies/ml (51%) in at least one sample. Higher viral loads were seen in patients with primary immunodeficiency and in those with cord blood transplant. Attributable symptoms were present in 12 patients (60%) concurrently with positive PCR. Clinical manifestations spontaneously resolved without treatment in most cases, concomitantly with a decrease in viral load. CONCLUSIONS: HHV-6 reactivation during allogeneic HSCT is common. HHV-6 reactivation should be considered in patients with graft-vs-host disease-like rash, onset of CNS symptoms, delay in engraftment, and in patients after cord blood transplantation.

The prevalence of human herpes viruses in the saliva of chronic periodontitis patients compared to oral health providers and healthy controls.

The causative agents in periodontal disease are periopathogenic bacteria; however, viruses have been implicated. The aim of this study was to examine the prevalence of different HHVs in the saliva of chronic periodontitis patients and to compare it to two groups of healthy controls. Three groups were included: chronic periodontitis patients (CP), periodontally healthy patients (NP) and oral health providers with a healthy periodontium (NPOHP). For each subject, 1 ml of unstimulated whole saliva was collected and mixed with 2 ml lysis buffer. HHVs assays were performed using real-time PCR. Fifteen percent of the subjects in the CP group tested positive for CMV compared to none in the NP and NPOHP groups (p = 0.04). Recurrent herpes was more frequent in females (51.7 %) than in males (33.3 %), and this was statistically significant (p = 0.038). The higher prevalence of CMV in the unstimulated saliva of CP patients suggests that CMV may play a role in the pathogenesis of chronic periodontitis.

Detection, control, and management of a respiratory syncytial virus outbreak in a pediatric hematology-oncology department.

BACKGROUND: Immunocompromised patients are at increased risk for severe respiratory syncytial virus (RSV) infection. Palivizumab is approved for prevention of RSV in specific populations but not for treatment. Few studies demonstrated the safety and successful treatment with intravenous (IV) palivizumab. We describe our experience with IV palivizumab treatment for RSV in a pediatric hematology-oncology department during an outbreak. METHODS: During a short period of renovations, oncology patients were placed in a general pediatric ward. After a case of severe fatal RSV pneumonia in a 2-year-old male patient with acute myeloid leukemia, all patients were actively screened twice weekly regardless of symptoms. Respiratory samples were tested for RSV using rapid immunochromatography detection, immunofluorescence, or reverse transcriptase polymerase chain reaction. A single dose of palivizumab (15 mg/kg) was given to children below 3 years of age who tested positive for RSV. RESULTS: Over a 6-week period, 12 patients tested positive for RSV. Seven patients were treated with palivizumab. Five patients had respiratory symptoms, and 2 were asymptomatic. No adverse events were attributed to IV palivizumab treatment. Early-treated patients had no complications attributed to RSV. CONCLUSIONS: Containment of RSV outbreak in high-risk children is difficult. Screening with reverse transcriptase polymerase chain reaction and the early use of IV palivizumab is safe and may prevent complications of RSV infection among these patients.

[HIV testing: the medical laboratory role in HIV diagnosis and monitoring].

Diagnosis of HIV infection is performed via enzyme immunoassay (EIA), an assay based on screening for antibodies against HIV. Confirmation of diagnosis is performed by Western-Blot, a more specific assay directed at a number of viral proteins for which antibodies exist. Routine follow-up of HIV-infected individuals includes measurement of CD4 cell count to evaluate the immune status, of viral load to assess virus replication, and of changes in the viral genome to characterize resistance to drugs and tropism. In addition, absence of the HLA B*57:01 allele is verified before prescription of abacavir, and drug levels of protease-inhibitors are determined in treatment-failing individuals after ruling out other causes of failure. Rapid diagnosis and regular follow-up improve the quality of life of patients and extend their life expectancy, also helping to control the spread of the epidemic at the national level.

Embryonic pig pancreatic tissue for the treatment of diabetes in a nonhuman primate model.

Xenotransplantation of pig tissues has great potential to overcome the shortage of organ donors. One approach to address the vigorous immune rejection associated with xenotransplants is the use of embryonic precursor tissue, which induces and utilizes host vasculature upon its growth and development. Recently, we showed in mice that embryonic pig pancreatic tissue from embryonic day 42 (E42) exhibits optimal properties as a beta cell replacement therapy. We now demonstrate the proof of concept in 2 diabetic Cynomolgus monkeys, followed for 393 and 280 days, respectively. A marked reduction of exogenous insulin requirement was noted by the fourth month after transplantation, reaching complete independence from exogenous insulin during the fifth month after transplantation, with full physiological control of blood glucose levels. The porcine origin of insulin was documented by a radioimmunoassay specific for porcine C-peptide. Furthermore, the growing tissue was found to be predominantly vascularized with host blood vessels, thereby evading hyperacute or acute rejection, which could potentially be mediated by preexisting anti-pig antibodies. Durable graft protection was achieved, and most of the late complications could be attributed to the immunosuppressive protocol. While fine tuning of immune suppression, tissue dose, and implantation techniques are still required, our results demonstrate that porcine E-42 embryonic pancreatic tissue can normalize blood glucose levels in primates. Its long-term proliferative capacity, its revascularization by host endothelium, and its reduced immunogenicity, strongly suggest that this approach could offer an attractive replacement therapy for diabetes.

Absence of APOL1 risk variants protects against HIV-associated nephropathy in the Ethiopian population.

BACKGROUND: Susceptibility to end-stage kidney disease (ESKD) among HIV-infected Americans of African ancestral heritage has been attributed to APOL1 genetic variation. We determined the frequency of the APOL1 G1 and G2 risk variants together with the prevalence of HIV-associated nephropathy (HIVAN) among individuals of Ethiopian ancestry to determine whether the kidney disease genetic risk is PanAfrican or restricted to West Africa, and can explain the previously reported low risk of HIVAN among Ethiopians. METHODS: We studied a cohort of 338 HIV-infected individuals of Ethiopian ancestry treated in one Israeli and one Ethiopian center. We sought clinical evidence for HIVAN (serum creatinine >1.4 mg/dl or proteinuria >30 mg/dl in a spot urine sample). Genetic analyses included the genotyping of the APOL1 G1 and G2 variants, and a panel of 33 genomic ancestry-informative markers. Statistical analysis compared clinical and genetic indices for HIV-infected individuals of Ethiopian ancestry and overall Ethiopians to those reported for HIV-infected African-Americans, overall African-Americans, West Africans and non-Africans. FINDINGS: Three (0.8%) of 338 HIV-infected patients of Ethiopian ancestry showed clinical criteria compatible with renal impairment. Two of these 3 patients also have severe poorly controlled diabetes mellitus. The third nondiabetic patient underwent renal biopsy which ruled out HIVAN. This absence of clinically apparent HIVAN was significantly different from that reported for African-Americans. The APOL1 G1 and G2 risk variants were found, respectively, in 0 and 2 (heterozygote state) of the 338 HIV-infected individuals. Global ancestry and the frequencies of the APOL1 G1 and G2 variants are not statistically different from their frequencies in the general Ethiopian population, but are significantly and dramatically lower than those observed among HIV-infected African-Americans, African-Americans and West Africans. INTERPRETATION: The coinciding absence of HIVAN and the APOL1 risk variants among HIV-infected individuals of Ethiopian ancestry support a Western rather than Pan-African ancestry risk for ESKD, and can readily explain the lack of HIVAN among individuals of Ethiopian ancestry.

Incidence and clinical manifestations of adenoviral infection among children undergoing allogeneic stem cell transplantation.

BACKGROUND: Adenoviral infection in children undergoing stem cell transplantation is associated with significant morbidity and mortality. Identification of adenoviral infection by polymerase chain reaction from blood facilitates accurate and rapid diagnosis and surveillance. The incidence of adenoviral infection among children undergoing SCT in Israel is not known. OBJECTIVE: To estimate the incidence of adenoviral infection in pediatric SCT patients and to characterize the morbidity associated with proven infection. METHODS: Blood samples obtained weekly from children who underwent allogeneic SCT were retrospectively tested for adenovirus using standard PCR. A total of 657 samples collected from 32 patients were examined. Correlation was made between the presence of adenovirus in samples and clinical records. RESULTS: Of the 32 patients 4 had adenoviral infection by PCR (12.5%). Clinical disease was present in all four patients concurrent with positive PCR. Gastrointestinal complaints and abnormal hepatocellular enzymes were uniformly present. One patient died due to disseminated disease. T cell depletion was a significant risk factor for adenoviral infection (P = 0.03). CONCLUSIONS: In the patient population studied, the incidence of adenoviral infection in children undergoing SCT was 12.5%. The combination of gastrointestinal symptoms and abnormal hepatocellular enzymes should raise the suspicion of adenoviral infection, especially when occurring during the first few months after SCT.

[The burden and outcomes of acute bronchiolitis among young children hospitalized in Israel].

BACKGROUND: Acute bronchiolitis (AB) is a significant indication for hospitalization during the winter period. Underlying conditions increase risk for severe manifestations. AIMS: To estimate the burden and outcomes of AB in northern Israel. METHODS: A prospective study was performed between 1.12.2005 - 31.3.2006. Previously healthy children younger than 2 years of age, hospitalized with the diagnosis of AB, in three hospitals in northern Israel, were included in this study. RESULTS: Overall, 465 children (93%) out of 500 children who were hospitalized due to AB and comprised 18% of all hospitalizations during the study period, were included. A pathogen was identified in 91% of cases. A single pathogen was identified in 243 (52%) cases; 2-4 pathogens were found in 176 (39%) children. Common pathogens were respiratory syncytial virus (RSV) and Rhinovirus in 346 (75%) and 129 (28%), of which 192 (41%) and 37 (8%) were sole pathogens respectively. Complete data were available for 390 (82%) children, of whom 78% were younger than 6 months. Patients were hospitalized for 4 +/- 4.4 days; 15 children were treated in intensive care. There was one mortality. An X-ray was performed in 94% of cases. Most children were treated with multiple regimens including intravenous fluids, O2 supplement, physiotherapy, bronchodilators, steroids and antibiotics. Bronchiolitis was attributed to 18% of hospitalizations. On a national scale, assuming that the policy of hospitalization is similar, 4100 children were hospitalized due to AB. This reflects 4% of all hospitalized children a year in Israel and attributing to 16,400 hospitalizations. CONCLUSIONS: AB is associated with a huge burden, during a short period of the year, on pediatric departments, mainly attributed by infants younger than 6 months of age. The development of effective vaccine against RSV may significantly reduce the burden of morbidity.

JC Viruria Is Associated With Reduced Risk of Diabetic Kidney Disease.

PURPOSE: African Americans who shed JC polyomavirus (JCV) in their urine have reduced rates of nondiabetic chronic kidney disease (CKD). We assessed the associations between urinary JCV and urine BK polyomavirus (BKV) with CKD in African Americans with diabetes mellitus. METHODS: African Americans with diabetic kidney disease (DKD) and controls lacking nephropathy from the Family Investigation of Nephropathy and Diabetes Consortium (FIND) and African American-Diabetes Heart Study (AA-DHS) had urine tested for JCV and BKV using quantitative PCR. Of the 335 individuals tested, 148 had DKD and 187 were controls. RESULTS: JCV viruria was detected more often in the controls than in the patients with DKD (FIND: 46.6% vs 32.2%; OR, 0.52; 95% CI, 0.29 to 0.93; P = 0.03; AA-DHS: 30.4% vs 26.2%; OR, 0.63; 95% CI, 0.27 to 1.48; P = 0.29). A joint analysis adjusted for age, sex, and study revealed that JC viruria was inversely associated with DKD (OR, 0.56; 95% CI, 0.35 to 0.91; P = 0.02). Statistically significant relationships between BKV and DKD were not observed. MAIN CONCLUSIONS: The results from the present study extend the inverse association between urine JCV and nondiabetic nephropathy in African Americans to DKD. These results imply that common pathways likely involving the innate immune system mediate coincident chronic kidney injury and restriction of JCV replication. Future studies are needed to explore causative pathways and characterize whether the absence of JC viruria can serve as a biomarker for DKD in the African American population.

Evaluation of the virtues and pitfalls in an HIV screening algorithm based on two fourth generation assays - A step towards an improved national algorithm.

BACKGROUND: Fourth-generation immunoassays used for HIV screening, simultaneously detect anti-HIV antibodies and HIV-1 P24 antigen, but are prone to false-positive results. Usually, they are followed by highly specific third-generation assay, able to differentiate between HIV-1/2 infections. In Israel, screening algorithm is based on consecutive testing by two fourth-generation assays and confirmation by a third-generation test. OBJECTIVES: To evaluate the performance of this algorithm. STUDY DESIGN: Architect HIV1/2 Combo (Combo) reactive results were tested by Vidas HIV Duo Ultra (VD). Confirmation was by INNO-LIA HIV 1/2 or Geenius assays. Five-year results were retrospectively analyzed. HIV true positives (TPs), acute infected (AI), false-positives (FPs) and HIV negatives, were as defined by the algorithm. RESULTS: 501,338 individuals were screened, of which 956 were TPs, 64 AI and 30 F Ps. Specificity was almost 100% and positive predictive value 97%. VD was negative in 94% of confirmed Combo false-reactive individuals. The Combo results in the first tested sample differed substantially between TPs, AI and FPs, enabling the determination of a cutoff value that distinguished 94% of TPs and AI from FPs. CONCLUSIONS: An algorithm is suggested that will use a single sample collection. HIV negative diagnosis will be based on Combo unreactive or Combo reactive/VD negative results. HIV positive diagnosis will be based on Combo reactive/ VD positive results, given a Combo value above a designated cutoff. Below this cutoff samples will be tested by a molecular assay. Since HIV-2 rarely occurs in Israel, the use of a third-generation confirmation assay should be discussed.

Diagnosis of HIV-1 infection: Performance of Xpert Qual and Geenius supplemental assays in fourth generation ELISA-reactive samples.

BACKGROUND: 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. OBJECTIVES: 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. STUDY DESIGN: 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. RESULTS: Overall, 94.1% (705/749) of AR-VD-reactive results were true HIV-1 positive. All samples with <3 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. CONCLUSIONS: 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.

Relationship between human herpesvirus 8 loads and disease stage in classic Kaposi sarcoma patients.

Human herpesvirus 8 (HHV-8), also known as Kaposi sarcoma (KS)-associated herpesvirus, is causally implicated in all forms of KS, including the classic form. Our objective was to investigate the relationship between HHV-8 load in peripheral blood mononuclear cells (PBMCs) and the stage of the disease in classic KS (CKS) patients. HHV-8 loads were measured in 41 PBMC samples from CKS patients with different Krigel-based classification stages using a quantitative real-time polymerase chain reaction assay. Low HHV-8 DNA loads reaching a maximum of 75.5 copies/10(5) cells were detected in 73.2% of the patients. HHV-8 loads in patients with stages I and II were similarly distributed. An increased detection rate of HHV-8 DNA, although not statistically significant, was evident in patients diagnosed with CKS stages III and IV. We conclude that the measurements of HHV-8 load in PBMCs provide a limited correlation with the clinical stage of KS.

Human enterovirus D68 in clinical and sewage samples in Israel.

BACKGROUND: Since mid-August 2014, North America experienced a wide outbreak of Enterovirus D68 (EV-D68) associated with severe respiratory illness in children. Several other countries also reported cases of EV-D68 in 2014. OBJECTIVES: The aim of this study was to determine whether EV-D68 circulated in Israel in 2014, caused severe respiratory illness in children and was the causative agent of Acute Flaccid Paralysis. STUDY DESIGN: Archived clinical respiratory samples from a cohort of 710 hospitalized pediatric patient's (<10years old) with respiratory illness were screened for clade B specific EV-D68 by real-time PCR. The patients were seen at four medical centers covering the entire country between August and November 2014. We also evaluated 49 patient stool samples from 26 AFP cases during 2014 for presence of EV-D68. In addition, RNA from sewage samples collected throughout Israel during the same study period was also tested for EV-D68. Partial VP1 sequencing was performed on all positive samples. RESULTS: Of the 710 clinical samples evaluated, 7 (1%) were positive for EV-D68. Two patients were from the central part of Israel, while the rest was from the southern part. The majority of the patients did not have any underlying disease. Not only that, but, none of the 26 suspected AFP cases had EV-D68 nucleic acid in their stool samples. EV-D68 RNA was detected in 9 out of 93 sewage samples, mainly from Southern Israel. Sequence analysis of EV-D68 VP1 gene from both sewage and clinical samples indicated that the Israeli EV-D68 RNA belonged to Clade B which was genetically similar to 2014 circulating European and North American EV-D68 virus. CONCLUSIONS: EV-D68 circulated in Israel during the 2014 summer-fall season and caused hospitalization of a small percent of the patients with respiratory illness.

HCV genotype-1 subtypes and resistance-associated substitutions in drug-naive and in direct-acting antiviral treatment failure patients.

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.

Sexually transmitted diseases among patients with human immunodeficiency virus in northern Israel.

BACKGROUND: The co-morbidity of human immunodeficiency virus and other sexually transmitted diseases in Israel has not been established. OBJECTIVES: To compare the prevalence of STDs among HIV-positive patients to HIV-negative patients visiting an STD clinic in northern Israel. METHODS: Between December 2000 and December 2001, 176 HIV-positive individuals (53% males) were screened and compared to 200 HIV-seronegative individuals (76% males). Demographics, symptomatology and risk factors were obtained via questionnaire. First-void urine samples were tested for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae. Serum was tested for type-specific herpes simplex virus-2, hepatitis B and syphilis. RESULTS: Relative to the seronegative STD patients, HIV-positive patients exhibited significantly greater risk-reducing sexual behaviors such as consistent condom use [29/86 (33.7%) vs. 16/187 (8.6%), P < 0.001], and abstinence in the previous 6 months [43/125 (34%) vs. 7/185 (3.8%), P < 0.001]. Nevertheless, STD prevalence was higher among HIV-positive than HIV-negative patients (79.5% vs 37.5%, P < 0.001). HSV-2, syphilis and HBV were more common among HIV-positive than HIV-negative patients [120/175 (68.8%)] vs. 18/200 (9%), P < 0.001)], [43/161 (26.7%) vs. 0%, P < 0.001)], [13/171 (7.6%) vs. 3/200 (1.5%), P < 0.01)], respectively. In contrast, Chlamydia and gonorrhea were more common in HIV-negative patients than HIV-positive patients [3/176 (1.7%) vs.13/200 (6.5%), P < 0.05] vs. [0% vs.5/200 (2.5%), P < 0.05], respectively. CONCLUSION: Despite the low risk sexual behavior of Israeli HIV patients, they had a high prevalence of chronic STDs (e.g., HSV-2, HBV and syphilis). The lower prevalence of Chlamydia and gonorrhea among HIV-immunosuppressed patients may be attributed to routine antibiotic prophylaxis against opportunistic infections. Nevertheless, as advocated by international health organizations, it appears prudent to recommend the routine screening of these asymptomatic HIV-positive patients for STD pathogens.