Lessons from intensified surveillance of viral hepatitis A, Israel, 2017 and 2018.

IntroductionUniversal vaccination of toddlers has led to very low hepatitis A (HAV) endemicity in Israel. However, sporadic outbreaks still occur, necessitating better surveillance.AimTo implement a comprehensive HAV surveillance programme.MethodsIn 2017 and 2018, sera from suspected HAV cases that tested positive for anti-HAV IgM antibodies were transferred to the Central Virology Laboratory (CVL) for molecular confirmation and genotyping. Sewage samples were collected in Israel and Palestine* and were molecularly analysed. All molecular (CVL), epidemiological (District Health Offices and Epidemiological Division) and clinical (treating physicians) data were combined and concordantly assessed.ResultsOverall, 146 cases (78 in 2017 and 68 in 2018, median age 34 years, 102 male) and 240 sewage samples were studied. Most cases (96%) were unvaccinated. In 2017, 89% of cases were male, 45% of whom were men who have sex with men (MSM). In 2018, 49% were male, but only 3% of them were MSM (p < 0.01). In 2017, 82% of cases and 63% of sewage samples were genotype 1A, phylogenetically associated with a global MSM-HAV outbreak. In 2018, 80% of cases and 71% of sewage samples were genotype 1B, related to the endemic strain previously identified in Israel and Palestine*. Environmental analysis revealed clustering of sewage and cases' sequences, and country-wide circulation of HAV.ConclusionsMolecular confirmation of HAV infection in cases and analysis of environmental samples, combined with clinical and epidemiological investigation, may improve HAV surveillance. Sequence-based typing of both clinical and sewage-derived samples could assist in understanding viral circulation.

Nuphar lutea Extracts Exhibit Anti-Viral Activity against the Measles Virus.

Different parts of Nuphar lutea L. (yellow water lily) have been used to treat several inflammatory and pathogen-related diseases. It has shown that Nuphar lutea extracts (NUP) are active against various pathogens including bacteria, fungi, and leishmanial parasites. In an effort to detect novel therapeutic agents against negative-stranded RNA (- RNA) viruses, we have tested the effect of a partially-purified alkaloid mixture of Nuphar lutea leaves on the measles virus (MV). The MV vaccine's Edmonston strain was used to acutely or persistently infect cells. The levels of several MV proteins were detected by a Western blot and immunocytochemistry. Viral RNAs were quantitated by qRT-PCR. Virus infectivity was monitored by infecting African green monkey kidney VERO cells' monolayers. We showed that NUP protected cells from acute infection. Decreases in the MV P-, N-, and V-proteins were observed in persistently infected cells and the amount of infective virus released was reduced as compared to untreated cells. By examining viral RNAs, we suggest that NUP acts at the post-transcriptional level. We conclude, as a proof of concept, that NUP has anti-viral therapeutic activity against the MV. Future studies will determine the mechanism of action and the effect of NUP on other related viruses.

A retrospective study on demographic and clinical characteristics of cutaneous leishmaniasis suspected cases in southern Israel, 2013-2016: Comparison between confirmed and negative cases.

BACKGROUND & OBJECTIVES: Clinical diagnosis of cutaneous leishmaniasis (CL) may bear a high rate of false diagnosis. This study assessed CL-suspected episodes, in an attempt to differentiate confirmed CL and non-CL diagnoses. METHODS: In this retrospective, case-control study, medical files of CL-suspected episodes, tested by a biopsy for Leishmania-PCR, from 2013 to 2016, were collected and analysed statistically. RESULTS: Of 324 suspected CL episodes, 48.8% were PCR-confirmed CL (96.2% Leishmania major) and 51.2% were non-CL (57.1% bacterial infections). Overall, 59.3% episodes were in males. Mean (± SD) duration until diagnosis was 3.7 ± 7.2 months. Lesions (mean 2.9 ± 3.8 per episode) were mostly (60.8%) sampled from September through February. Ulcer, pain, itching, purulent discharge and fever were recorded in 55.2, 47, 42.9, 18.2 and 4.7% of episodes, respectively. Univariate analysis showed that male gender, multiple lesions, ulcer, >1-month duration until diagnosis, and seasonality were associated with CL. Empiric CL treatment was recorded in 63.4 and 16% of CL-confirmed and non-CL episodes, respectively (p <0.001); and was observed to be associated with Jewish ethnicity, seasonality, multiple lesions, ulcer, absence of fever and duration of >1-month until diagnosis. In multivariate analysis, seasonality (odds ratio, OR = 2.144), empiric CL treatment (OR = 5.144) and ulcer (OR = 2.459) were associated with CL. Empiric CL treatment was associated with Jewish ethnicity (OR = 2.446) and duration of >1-month until diagnosis (OR = 3.304). INTERPRETATION & CONCLUSION: CL diagnosis should be laboratory confirmed, as clinical appearance is often misleading. Seasonality, ulcer appearance and gender may aid in correct identification and treatment of CL cases.

The impact of incorporating early rapid influenza diagnosis on hospital occupancy and hospital acquired influenza.

OBJECTIVE: To assess the impact of incorporating early rapid influenza diagnosis on antimicrobial usage, nosocomial influenza transmission, length of stay, and occupancy rates among hospitalized patients. SETTING: A 1,100 bed tertiary-care hospital in southern Israel. METHODS: We implemented early rapid detection of influenza with immediate communication of results. Using Orion methods, we compared the 2017-2018 influenza season to the prior season in our hospital and to the 2017-2018 occupancy rates at other Israeli hospitals. RESULTS: During the intervention season, 5,006 patients were admitted; 1,824 were tested for influenza, of whom 437 (23.9%) were positive. In the previous season, 4,825 patients were admitted; 1,225 were tested and 288 (23.5%) were positive. Time from admission to test report decreased from 35.5 to 18.4 hours (P < .001). Early discharge rates significantly increased, from 21.5% to 41.6% at 36 hours, from 37.2% to 54.5% at 48 hours, and from 66% to 73.2% at 72 hours. No increase in repeat ER visits, readmission, or mortality rates was observed. Hospital occupancy decreased by 10% compared to the previous year and was 26% lower than the national rate. Hospital-acquired influenza cases were reduced from 37 (11.4%) to 12 (2.7%) (P < .001). Antibiotic usage was reduced both before and after notification of test results by 16% and 12%, respectively. CONCLUSIONS: Implementing this intervention led to earlier discharge of patients, lower occupancy in medical wards, reduced antibiotic administration, and fewer hospital-acquired influenza events. This strategy is useful for optimizing hospital resources, and its implementation should be considered for upcoming influenza seasons.

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.

Comparable long-term efficacy of Lopinavir/Ritonavir and similar drug-resistance profiles in different HIV-1 subtypes.

BACKGROUND: Analysis of potentially different impact of Lopinavir/Ritonavir (LPV/r) on non-B subtypes is confounded by dissimilarities in the conditions existing in different countries. We retrospectively compared its impact on populations infected with subtypes B and C in Israel, where patients infected with different subtypes receive the same treatment. METHODS: Clinical and demographic data were reported by physicians. Resistance was tested after treatment failure. Statistical analyses were conducted using SPSS. RESULTS: 607 LPV/r treated patients (365 male) were included. 139 had HIV subtype B, 391 C, and 77 other subtypes. At study end 429 (71%) were receiving LPV/r. No significant differences in PI treatment history and in median viral-load (VL) at treatment initiation and termination existed between subtypes. MSM discontinued LPV/r more often than others even when the virologic outcome was good (p = 0.001). VL was below detection level in 81% of patients for whom LPV/r was first PI and in 67% when it was second (P = 0.001). Median VL decrease from baseline was 1.9±0.1 logs and was not significantly associated with subtype. Median CD4 increase was: 162 and 92cells/µl, respectively, for patients receiving LPV/r as first and second PI (P = 0.001), and 175 and 98, respectively, for subtypes B and C (P<0.001). Only 52 (22%) of 237 patients genotyped while under LPV/r were fully resistant to the drug; 12(5%) were partially resistant. In48%, population sequencing did not reveal resistance to any drug notwithstanding the virologic failure. No difference was found in the rates of resistance development between B and C (p = 0.16). CONCLUSIONS: Treatment with LPV/r appeared efficient and tolerable in both subtypes, B and C, but CD4 recovery was significantly better in virologically suppressed subtype-B patients. In both subtypes, LPV/r was more beneficial when given as first PI. Mostly, reasons other than resistance development caused discontinuation of treatment.

Influenza A/H1N1 in pediatric oncology patients.

BACKGROUND: Our aim was to determine the clinical and epidemiological features of pandemic influenza A/H1N1 in immunocompromised children with solid tumors and hematological malignancies. PATIENTS AND METHODS: A prospective study was conducted during the H1N1 pandemic between August 2009 and February 2010 in a pediatric hematology-oncology unit. Demographic and clinical data were obtained from all children with suspected H1N1 infection (high fever with or without respiratory symptoms). Laboratory diagnosis of influenza A/H1N1 was performed by means of polymerase chain reaction analysis of nasopharyngeal wash specimens. RESULTS: We identified 57 episodes of suspected influenza A/H1N1 infection in 40 children. In all episodes, children were treated with oseltamivir and antibiotics until influenza A/H1N1 results were received. Of all episodes, 13 (22.8%) tested positive for influenza A/H1N1. Two of the H1N1-positive children (15.4%) had been previously immunized against influenza A/H1N1. No differences between H1N1-positive and H1N1-negative children were noted in terms of demographic features, clinical presentation, laboratory findings, and underlying disease.Three polymerase chain reaction-positive (23.0%) children and 1 H1N1-negative (2.3%) child were admitted to the pediatric intensive care unit and were mechanically ventilated (P=0.03). One (7.7%) H1N1-positive patient died versus none of the H1N1-negative patients (P=0.2). The condition of all other children in both the groups improved rapidly during hospitalization. CONCLUSIONS: Febrile hospitalized pediatric oncology patients, with and without pandemic influenza A/H1N1, had a similar demographic and clinical presentation with a relatively good outcome. This was probably because of early antiviral treatment and possibly because of the relatively low virulence of the virus. Immunization should be encouraged in these patients.

[Prevalence of sexually transmitted diseases (STD) in HIV positive women in southern Israel].

BACKGROUND: Co-infection of HIV and other sexualLy transmitted diseases (STDs) is common. The Centers for Disease Control and Prevention (CDC) recommends routine yearly screening for STDs in HIV carriers. There is only scarce data on the prevalence of STD in HIV positive individuals in Israel and no current recommendations on this issue are available. OBJECTIVES: To evaluate the prevalence of STDs, in HIV positive females attending the HIV Clinic at the Soroka University Medical Center in Beer Sheva and to compare prevalence and risk factors for STDs between HIV female carriers of Ethiopian and non-Ethiopian origin. METHODS: Eighty five HIV-positive women were enrolled in the study. Demographic data and sexual behavior were obtained and medical records were reviewed. Cervical swabs for Neisseria gonorrhoeae, Herpes simplex 1 and 2, Ureaplasma urealyticum and Mycoplasma hominis and serum samples for hepatitis B, C and syphilis were obtained. RESULTS: Thirty two of the study participants (37.6%) had at least one STD and in eleven cases (12.9%) two or more STDs were found. Ureaplasma urealyticum was the most frequent pathogen (29.4%). Prevalence for Mycoplasma hominis, HSV1 and 2, Neisseria gonorrhoeae, syphilis and HBV was low. Despite significant differences in sexual behavior between women of Ethiopian and non-Ethiopian origin there were no differences in the prevalence of STDs in the two groups. HCV was significantly more prevalent in women of non-Ethiopian origin, due to high use of intravenous drugs in this group. There was no correlation between CD4 levels and the prevalence of STDs in both groups. DISCUSSION AND CONCLUSION: A relatively low prevalence of STDs among female HIV carriers was found, despite low condom use. The exclusion of males in this study may have contributed to this. The most frequent pathogen found in this study was asymptomatic Ureaplasma urealyticum (29.4%). As this pathogen may cause premature delivery and fetal death it seems important to routinely screen HIV-positive fertile women for its presence. A nationwide multicenter study of HIV-positive females and males is needed in order to establish the prevalence of STDs in this population in Israel and to recommend a screening policy.

Risk factors for community-acquired pneumonia with influenza A/H1N1 in southern Israel.

OBJECTIVES: To determine the risk factors for community-acquired pneumonia (CAP) with influenza A/H1N1 flu in our region. METHODS: Adult patients with CAP from July 2009 to February 2010 who were screened for influenza A/H1N1 were identified retrospectively. This was a retrospective case-control study. Cases had CAP with influenza A/H1N1 and controls had CAP without influenza A/H1N1. Patient files were reviewed for demographics, clinical characteristics, treatment, and outcome. RESULTS: Three hundred and eight patients with CAP were identified: 107 cases and 201 controls. For cases vs. controls there were significant differences in the following: median age (40 (range 18-82) vs. 56 (range 18-89) years; p<0.001), female gender (63.6% vs. 44.3%; p<0.05), Bedouin Arab origin (41.1% vs. 26.4%; p<0.05), pyrexia (97.6% vs. 88.5%; p<0.01), cough (96.3% vs. 75%; p<0.05), admission to the intensive care unit (18.7% vs. 10.6%; p<0.05), and CURB-65 score ≥ 3 (2.8% vs. 11.4%; p<0.05). Laboratory values including white blood cell (WBC) and platelet counts were lower in cases than in controls, whereas creatine phosphokinase and lactate dehydrogenase levels were higher (p<0.01). By logistic regression models, young age, Bedouin origin, and lower WBC and platelet counts were independent risk factors for the acquisition of CAP with influenza A/H1N1. CONCLUSIONS: In our region CAP with influenza A/H1N1 occurred in younger females of Bedouin Arab origin with less co-morbidity. No difference in mortality was found. We believe that inequalities in socioeconomic conditions could explain our findings.