Yonat Shemer-Avni

Comparison of human metapneumovirus, respiratory syncytial virus and influenza a virus lower respiratory tract infections in hospitalized young children

Background: We compared the clinical and demographic features of children with lower respiratory tract infection (LRI) caused by human metapneumovirus (HMPV), respiratory syncytial virus (RSV) and influenza A virus and sought to determine whether coinfection by HMPV and other respiratory viruses leads to increased disease severity. Methods: Nasal wash specimens were prospectively obtained from 516 children hospitalized for LRI during a 1-year period and tested for the presence of HMPV by reverse transcription-polymerase chain reaction and for RSV and influenza A by direct immunofluorescence. Results: HMPV was detected in 68 (13%) patients and was the third most common viral pathogen; 16 of 68 HMPV-positive children (24%) had coinfection with other respiratory viruses (HMPVco). HMPV patients were older than RSV patients (17.6 ± 16.8 months versus 10.5 ± 11.8 months, P = 0.02). HMPV was associated with wheezing and hypoxemia at a rate similar to that of RSV and higher than that of influenza A. Atelectasis was more common among HMPV (40%) than among RSV and influenza patients (13%, P < 0.05 for each). HMPV infection was more often associated with a diagnosis of pneumonia than RSV and influenza A and was more often associated with a diagnosis of asthma and less often associated with a diagnosis of bronchiolitis than RSV infection (P < 0.05 for each), even when corrected for age. Children with HMPVco had a higher rate of gastrointestinal symptoms but did not show a more severe respiratory picture. Conclusions: The clinical pattern of HMPV more closely resembles that of RSV than that of influenza A LRI, yet the differences in age, radiographic findings and clinical diagnosis suggest that HMPV pathogenesis may differ from that of RSV.

Copper Oxide Impregnated Textiles with Potent Biocidal Activities

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.

Global Genetic Diversity of Human Metapneumovirus Fusion Gene

We analyzed 64 human metapneumovirus strains from eight countries. Phylogenetic analysis identified two groups (A and B, amino acid identity 93%–96%) and four subgroups. Although group A strains predominated, accounting for 69% of all strains, as many B as A strains were found in persons >3 years of age.

Respiratory Viruses in Adults With Community-Acquired Pneumonia

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.

Identification of Respiratory Viruses in Adults: Nasopharyngeal versus Oropharyngeal Sampling

ABSTRACT The optimal method for identifying respiratory viruses in adults has not been established. The objective of the study was to compare the sensitivities of three sampling methods for this purpose. One thousand participants (mean age, 63.1 ± 17.8 years) were included. Of these, 550 were patients hospitalized for acute febrile lower respiratory tract infections and 450 were controls. Oropharyngeal swabs (OPS), nasopharyngeal swabs (NPS), and nasopharyngeal washings (NPW) were obtained from each participant and were tested for 12 respiratory viruses by a multiplex hydrolysis probes-based quantitative real-time reverse transcription-PCR. Patients were defined as positive for a specific virus if the virus was identified by at least one sampling method. In all, 251 viruses were identified in 244 participants. For the detection of any virus, the sensitivity rates for OPS, NPS, and NPW were 54.2%, 73.3%, and 84.9%, respectively (for OPS versus NPS and NPW, P < 0.00001; for NPS versus NPW, P < 0.003). Maximal sensitivity was obtained only with sampling by all three methods. The same gradation of sensitivity for the three sampling methods was found when influenza viruses, coronaviruses, and rhinoviruses were analyzed separately. The three sampling methods yielded equal sensitivity rates for respiratory syncytial virus. We conclude that nasopharyngeal sampling has a higher rate of sensitivity than oropharyngeal sampling and that the use of NPW has a higher rate of sensitivity than the use of NPS with a rigid cotton swab for the identification of respiratory viruses in adults. Sampling by all three methods is required for the maximal detection of respiratory viruses.

Identification of Risk Factors for Infection in an Outbreak of Mycoplasma pneumoniae Respiratory Tract Disease

BACKGROUND Mycoplasma pneumoniae is one of the most common pathogens that causes community-acquired respiratory tract infection. Outbreaks are well known, and all age groups are susceptible. An outbreak in an army training unit afforded an opportunity to identify possible risk factors for morbidity. METHODS An outbreak of respiratory illness that occurred in a unit comprising 91 trainees was investigated and analyzed as a cohort study. M. pneumoniae infection was suspected on clinical grounds and was confirmed by polymerase chain reaction, culture, and serologic testing. Data regarding medical history, symptoms, signs, and laboratory tests were collected. RESULTS During a period of 12 days, 41 soldiers (45.1%) had respiratory illnesses, of which 10 (11.0%) were pneumonia. Comparison of symptomatic and asymptomatic individuals revealed that smoking was associated with higher rates of disease (risk ratio, 2.1; 95% confidence interval [CI], 1.3-3.2; P<.005) and seroconversion (risk ratio, 2; 95% CI, 1.2-3.4; P=.03). In multivariate analysis, both lower acute immunoglobulin G values (adjusted odds ratio, 7.8; 95% CI, 1.4-42.5; P=.018) and smoking (adjusted odds ratio, 5.6; 95% CI, 1.5-20.4; P=.01) were associated with symptomatic infection; stratification according to smoking status revealed that immunoglobulin G levels among nonsmokers were protective. Patients who had pneumonia had lower lymphocyte counts (1400+/-258 vs. 2000+/-465 cells/microL; P=.001). CONCLUSIONS Smoking and lower preexisting immunoglobulin G levels were strongly associated with M. pneumoniae respiratory infection. These findings emphasize the importance of immunity and cessation of smoking for the prevention of disease. The high attack rate emphasizes the extent of infection transmission among healthy persons living in close contact.

Hepatitis C virus infection in renal failure patients in the absence of anti-hepatitis C virus antibodies

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.

HCV antibodies in saliva and urine

Infection with hepatitis C virus (HCV) is usually established by detection of serum antibodies (anti‐HCV). This study was conducted in order to evaluate whether saliva and urine may substitute serum for anti‐HCV detection. Serum, saliva, and urine were obtained simultaneously from 141 patients with a variety of liver diseases and from 52 patients with autoimmune diseases (systemic lupus erythematosus n = 27 and rheumatoid arthritis n = 25). The cell free fraction of saliva and urine samples was tested for anti‐HCV using a modification of a serum anti‐HCV kit. Western blot analysis was used as a confirmation method. Of the patients with liver diseases, 73 were anti‐HCV‐seropositive. Salivary and urinary anti‐HCV could be detected in 66 (90%) and 36 (49%) of the anti‐HCV‐serpositive patients, respectively. The presence of anti‐HCV in saliva or urine was not related to the severity of liver disease. All the anti‐HCV‐seronegative liver patients were negative for salivary anti‐HCV and 22 (32%) had urinary anti‐HCV. The patients with autoimmune diseases were all anti‐HCV‐seronegative. None had detectable salivary anti‐HCV while 33 (63%) were positive for urinary anti‐HCV. Western Blot analysis confirmed the presence of anti‐HCV in all serum and saliva samples tested but only in 2/12 urine samples. The results suggest that saliva, but not urine, may serve as a substitute for serum for the determination of anti‐HCV positivity. J. Med. Virol. 55:24–27, 1998.

Hepatitis C virus infection and genotypes in Southern Israel and the Gaza strip

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 1b 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). J. Med. Virol. 56:230–233, 1998.

Modulation of hepatitis C virus release by the interferon-induced protein BST-2/tetherin.

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.