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Biomedical subjects

Robert L Atmar

Publications and source records attributed to Robert L Atmar.

At least 19 recordsLinked to original sources
PubMed2026

Culture of infectious human norovirus isolated from live contaminated oysters.

Human noroviruses are a major cause of foodborne outbreaks worldwide. Filter-feeding shellfish, such as oysters, can bioaccumulate these viruses in their digestive tissue when grown in sewage-impacted coastal areas and are often implicated in norovirus foodborne outbreaks. Despite the high sensitivity of current molecular assays, these methods for norovirus detection in shellfish fail to distinguish between infectious and non-infectious particles. Assessing norovirus infectivity in shellfish remains a challenge due to the lack of suitable isolation methods that maintain capsid integrity. In this study, a protocol for isolating infectious norovirus from oyster tissues, based on chloroform-butanol elution and polyethylene glycol concentration (CB-PEG), was optimized for the recovery of human norovirus GI and GII. While CB-PEG method recovered various norovirus GI and GII genotypes, it was less efficient at the genomic level than a protocol based on proteinase K elution (adapted from ISO 15216) and showed genotype-dependent viral recovery rates. By optimizing the flocculation step, we improved the method's compatibility with human intestinal enteroid (HIE) cultures. Using this approach, we successfully quantified infectious norovirus GII.3 titers recovered from artificially-contaminated live oysters. Interestingly, infectious virus was better isolated following a freezing step of the digestive tissues, with titers ranging from 13 to 40 TCID50/mL for positive samples. In conclusion, this study established an optimized methodological approach for the relative quantification of infectious norovirus GII.3 in shellfish, paving the way for future research on viral persistence and inactivation strategies in this foodstuff.

Norovirus↗
PubMed2007

Oral step-down therapy is comparable to intravenous therapy for Staphylococcus aureus osteomyelitis.

BACKGROUND: We hypothesized that regimens with an early switch to oral antibiotics are as effective as prolonged parenteral regimens for staphylococcal osteomyelitis. METHODS: We retrospectively reviewed records of adult patients with osteomyelitis caused by Staphylococcus aureus as determined by sterile site cultures, who had at least 6 months of follow-up post-therapy. The population was divided into two treatment groups: (1) an intravenous group (i.v.) that received > or = 4 weeks of parenteral therapy, and (2) a switch group that received < 4 weeks of intravenous followed by oral therapy. RESULTS: A total of 72 patients (36 in each group) were identified with groups evenly matched for demographic and clinical characteristics. The overall apparent cure rate was 74%; 69% for the i.v. group and 78% for the switch group (P=0.59). Apparent cure rates were similar regardless of duration of intravenous therapy: 83% < 2 weeks, 72% 2-4 weeks, 75% 4-6 weeks and 66% > or = 6 weeks (P=0.68). Among the 39 patients who received rifampin-based combinations, those treated simultaneously with vancomycin and rifampin did significantly worse than those who received other rifampin combinations (P<0.02). Overall, MRSA infections responded poorly compared to MSSA (65% apparently cured versus 83%). However, 11/14 (79%) MRSA patients who received rifampin combinations, other than vancomycin and rifampin simultaneously, were apparently cured. CONCLUSIONS: Overall outcomes did not differ significantly between i.v. and switch groups. Given the markedly lower costs and ease of administration, prolonged oral regimens after initial intravenous therapy may be a preferred regimen for staphylococcal osteomyelitis.

Administration, Oral↗
PubMed2006

Safety and immunogenicity of nonadjuvanted and MF59-adjuvanted influenza A/H9N2 vaccine preparations.

BACKGROUND: Influenza A/H9N2 viruses can infect humans and are considered to be a pandemic threat. Effective vaccines are needed for these and other avian influenza viruses. METHODS: We performed a phase I, randomized, double-blind trial to evaluate the safety and immunogenicity of a 2-dose schedule (administered on days 0 and 28) of 4 dose levels (3.75, 7.5, 15, and 30 microg of hemagglutinin) of inactivated influenza A/chicken/Hong Kong/G9/97 (H9N2) vaccine with and without MF59 adjuvant. Vaccine safety was assessed with a diary and selected blood tests. Immunogenicity was measured using serum hemagglutination inhibition (HAI) and microneutralization (MNt) antibody assays. RESULTS. Ninety-six healthy adults (age, 18-34 years) were enrolled in the study. Arm discomfort was more common in groups that received adjuvant, but adverse effects of the vaccination were generally mild. Geometric mean serum HAI and MNt antibody titers to the influenza A/chicken/Hong Kong/G9/97 (H9N2) virus strain for all vaccine groups were similar on day 0 but were significantly higher (P<.001) on both days 28 and 56 for the MF59-adjuvanted vaccine groups than for groups given nonadjuvanted vaccine. Other measures of immunogenicity were also higher in the adjuvanted vaccine groups. HAI and MNt geometric mean titers measured after the administration of a single dose of MF59-adjuvanted vaccine were similar to those measured after 2 doses of nonadjuvanted vaccine. CONCLUSIONS: The combination of MF59 adjuvant with a subunit vaccine was associated with improved immune responses to an influenza A/H9N2 virus. The adjuvanted vaccine was immunogenic even after a single dose, raising the possibility that a 1-dose vaccination strategy may be attainable with the use of adjuvanted vaccine.

Adjuvants, Immunologic↗
PubMed2006

Safety of high doses of influenza vaccine and effect on antibody responses in elderly persons.

BACKGROUND: Immune responses after influenza immunization are reduced in elderly individuals, the group at greatest risk for complications and death after influenza. Improved vaccines are needed to address this problem. METHODS: Ambulatory individuals 65 years and older (N = 202) were assigned randomly to receive a single intramuscular injection of the 2001-2002 formulation of trivalent inactivated influenza vaccine containing 15, 30, or 60 microg of hemagglutinin per strain (up to 180 microg total per dose) or placebo. Clinical and serologic responses were assessed during the month after immunization. RESULTS: Increasing dosages of vaccine elicited significantly higher serum antibody levels, frequencies of antibody responses, and putative protective titers after vaccination. Mean serum hemagglutination inhibition antibody titers 1 month after immunization in groups given 0-, 15-, 30-, and 60-microg dosages were 23, 37, 50, and 61 against influenza A/H1N1; 43, 86, 91, and 125 against influenza A/H3N2; and 10, 14, 18, and 24 against influenza B, respectively. Mean serum hemagglutination inhibition and neutralizing antibody levels against the 3 vaccine antigens in participants given the 60-microg dosage were 44% to 71% and 54% to 79%, respectively, higher than those in participants given the standard 15-microg dosage, and the 60-microg dosage level nearly doubled the frequency of antibody responses in those whose preimmunization antibody titers were in the lower half of the antibody range. Dose-related increases in the occurrence of injection site reactions were observed (P<.001), but all dosages were well tolerated. CONCLUSION: The improved immunogenicity of high-dose influenza vaccine among elderly persons should lead to enhanced protection against naturally occurring influenza.

Aged↗
PubMed2006

Recovery of drug-resistant influenza virus from immunocompromised patients: a case series.

Influenza virus with resistance to antiviral drugs emerges with increased frequency in immunocompromised patients and can limit the benefit of M2 and neuraminidase (NA) inhibitors. We document 3 cases of influenza in severely immunocompromised patients from whom virus variants with molecular markers of resistance to anti-influenza drugs were recovered. Virus variants recovered from 2 patients had mutations in the M2, NA (with a previously recognized Glu119Val NA substitution), and hemagglutinin genes. We describe a novel Asp198Asn NA mutation in an influenza B virus and its decreased susceptibility to both oseltamivir and zanamivir.

Antiviral Agents↗
PubMed2006

The epidemiologic and clinical importance of norovirus infection.

Noroviruses are a major cause of sporadic cases and epidemic outbreaks of gastroenteritis. The development of molecular diagnostic assays has led to an increased recognition of the significance of these viruses as causes of gastroenteritis in all age groups. This article reviews the epidemiology, clinical manifestations and pathogenesis of norovirus infection, and it describes the diagnostic and therapeutic approaches to this disease.

Caliciviridae Infections↗
PubMed2006

Noroviruses everywhere: has something changed?

PURPOSE OF REVIEW: Noroviruses causing gastroenteritis in humans have increasingly been described in both the scientific literature and the lay press. This review summarizes new information about where and why these viruses are detected as well as new developments to prevent or treat these infections. RECENT FINDINGS: Noroviruses are highly infectious and quite stable. Noroviruses infect all age groups, with particularly severe disease occurring in young children, the elderly, and persons with chronic diseases. Noroviruses also cause persistent infections in immunosuppressed patients. Host susceptibility factors have been identified, including histo-blood group antigens that likely function as initial receptors for some noroviruses. The patterns of susceptibility are complex, however, and not completely understood for all virus strains. X-ray crystallographic information on the virus capsid and other viral-encoded proteins provides targets for structure-based drug development. SUMMARY: The availability of new methods of detecting noroviruses has resulted in increased detection of these pathogens. Advances in understanding of virus replication and structure should lead to development of strategies to prevent and treat these infections. Such efforts may be challenged by the emergence of new virus strains that appear through mechanisms that remain to be understood.

Antiviral Agents↗
PubMed2006

Influenza vaccine in patients with asthma.

Influenza virus continues to be a major cause of respiratory infection and is an important contributor to morbidity and mortality in at-risk populations, including those with underlying pulmonary conditions such as asthma. Vaccination with inactivated influenza vaccine remains the most popular method in controlling influenza through prevention. Current guidelines recommend the administration of the influenza vaccine to all patients with asthma. However, a third or fewer of those patients with asthma are currently receiving this vaccine. In this review, the risk-versus-benefit of influenza vaccination in children and adults with asthma is evaluated, based on the current evidence.

Asthma↗
PubMed2006

Norwalk virus-specific binding to oyster digestive tissues.

The primary pathogens related to shellfish-borne gastroenteritis outbreaks are noroviruses. These viruses show persistence in oysters, which suggests an active mechanism of virus concentration. We investigated whether Norwalk virus or viruslike particles bind specifically to oyster tissues after bioaccumulation or addition to tissue sections. Since noroviruses attach to carbohydrates of the histo-blood group family, tests using immunohistochemical analysis were performed to evaluate specific binding of virus or viruslike particles to oyster tissues through these ligands. Viral particles bind specifically to digestive ducts (midgut, main and secondary ducts, and tubules) by carbohydrate structures with a terminal N-acetylgalactosamine residue in an alpha linkage (same binding site used for recognition of human histo-blood group antigens). These data show that the oyster can selectively concentrate a human pathogen and that conventional depuration will not eliminate noroviruses from oyster tissue.

ABO Blood-Group System↗
PubMed2005

Replication and packaging of Norwalk virus RNA in cultured mammalian cells.

Human noroviruses, the most common cause of nonbacterial gastroenteritis, are characterized by high infectivity rate, low infectious dose, and unusually high stability outside the host. However, human norovirus research is hindered by the lack of a cell culture system and a small animal model of infection. Norwalk virus (NV) is the prototype strain of human noroviruses. We report here replication of NV viral RNA and its packaging into virus particles in mammalian cells by intracellular expression of native forms of NV viral RNA devoid of extraneous nucleotide sequences derived from the expression vector by the use of replication-deficient vaccinia virus MVA encoding the bacteriophage T7 RNA polymerase (MVA/T7). Expressed genomic RNA was found to replicate; NV subgenomic RNA was transcribed from genomic RNA by use of NV nonstructural proteins expressed from genomic RNA and was subsequently translated into NV capsid protein VP1. Viral genomic RNA was packaged into virus particles generated in mammalian cells. The cesium chloride (CsCl) density gradient profile of virus particles containing genomic RNA was similar to that of NV purified from stool. These observations indicate that the NV cDNA constructed here is a biologically infectious clone, and that mammalian cells have the ability to replicate NV genomic RNA. This work establishes a mammalian cell-based system for analysis of human norovirus replication and, thus, makes it feasible to investigate antiviral agents in mammalian cells.

Animals↗
PubMed2005

The role of immune reconstitution inflammatory syndrome in AIDS-related Cryptococcus neoformans disease in the era of highly active antiretroviral therapy.

This study of human immunodeficiency virus (HIV)-infected patients coinfected with Cryptococcus neoformans found that 30% of patients who initiated highly active antiretroviral therapy developed immune reconstitution inflammatory syndrome (IRIS). Patients with C. neoformans-related IRIS had higher cerebrospinal fluid opening pressures, glucose levels, and white blood cell counts, compared with patients with typical HIV-associated C. neoformans meningitis.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Norwalk virus infection associates with secretor status genotyped from sera.

ABO histo-blood group type and secretor status are two genetically determined factors that contribute to resistance and susceptibility to Norwalk virus (NV). Archived serum samples but not saliva samples are available from NV and many other norovirus challenge studies and outbreaks. A person's ABO phenotype is easily determined from their archived sera, but the individual's secretor phenotype cannot easily be ascertained without saliva. We now report that a person's secretor genotype can also be determined from the archived serum samples. Of the 51 volunteers who participated in a NV challenge study, all eight non-secretors were resistant to NV infection, all of the 42 NV-infected volunteers were secretor positive, and a single uninfected secretor was histo-blood group type B. In agreement with a previous report, secretor status was most predictive of risk of NV infection. The methods described in this report should rapidly improve our knowledge of the associations between carbohydrate antigen expression and susceptibility to different strains of the non-cultivatable noroviruses by enabling retrospective studies from previously collected volunteer challenge and outbreak sera.

ABO Blood-Group System↗
PubMed2005

Bacteraemia in the elderly: predictors of outcome in an urban teaching hospital.

OBJECTIVES: To analyze the underlying factors of mortality in elderly adults with bacteraemia. METHODS: The study included 238 episodes of bacteraemia in an urban public teaching hospital. Retrospective chart review recorded demographic information, comorbid conditions, length of stay, source of infection, and physiologic and laboratory data on admission. RESULTS: Of the 238 episodes of bacteraemia, 128 patients were 65-74 years of age and 110 patients were > or =75 years of age. Eighty-one percent came from home. Fifty-four percent had Gram positive cocci detected in blood cultures and 36% had Gram negative bacilli. Factors associated with increased odds of mortality included underlying renal disease, admission to MICU, hypotension and hypoalbuminemia. Decreased odds of mortality were associated with being admitted from home and receiving appropriate antibiotics. CONCLUSIONS: Bacteraemia in the elderly has a high mortality rate, but is not significantly increased in those >or =75 years of age. The recent microbiology has shifted from Gram negative bacilli to Gram positive cocci. Physiologic abnormalities on admission predict worse outcomes in the elderly bacteraemic patient. Hypoalbuminemia on admission is associated with higher mortality rates in the elderly.

Aged↗
PubMed2005

Respiratory viral infections in patients with chronic, obstructive pulmonary disease.

OBJECTIVES: The purpose of the present study was to apply reverse transcription-PCR (RT-PCR) assays to clinical specimens collected from patients with acute respiratory illness and chronic obstructive pulmonary disease (COPD). METHODS: One hundred and ninety-four samples from two different study cohorts were analysed using RT-PCR assays for picornaviruses, coronaviruses 229E and OC43, influenza A and B viruses, respiratory syncytial virus, parainfluenza types 1-3 viruses, and human metapneumovirus and a PCR assay for adenoviruses. The results were added to results obtained previously using cell culture and serologic methods. RESULTS: RT-PCR assays identified an additional 35 respiratory virus-associated illnesses not identified previously by cell culture or serology (n=46). Picornaviruses and coronaviruses were the most common viral infections identified only by RT-PCR. Overall, 41.8% of the acute respiratory illnesses evaluated were associated with a respiratory virus infection, with picornaviruses, coronaviruses and influenza viruses being the most common infections recognized. No human metapneumovirus infections were identified by RT-PCR assay. CONCLUSIONS: Respiratory viral infections are commonly associated with acute respiratory illness in COPD patients, and the use of RT-PCR assays significantly increases the ability to diagnose these infections.

Aged↗
PubMed2005

Use of rotavirus virus-like particles as surrogates to evaluate virus persistence in shellfish.

Rotavirus virus-like particles (VLPs) and MS2 bacteriophages were bioaccumulated in bivalve mollusks to evaluate viral persistence in shellfish during depuration and relaying under natural conditions. Using this nonpathogenic surrogate virus, we were able to demonstrate that about 1 log10 of VLPs was depurated after 1 week in warm seawater (22 degrees C). Phage MS2 was depurated more rapidly (about 2 log10 in 1 week) than were VLPs, as determined using a single-compartment model and linear regression analysis. After being relayed in the estuary under the influence of the tides, VLPs were detected in oysters for up to 82 days following seeding with high levels of VLPs (concentration range between 10(10) and 10(9) particles per g of pancreatic tissue) and for 37 days for lower contamination levels (10(5) particles per g of pancreatic tissue). These data suggest that viral particles may persist in shellfish tissues for several weeks.

Animals↗
PubMed2004

Inactivated influenza vaccination for people with spinal cord injury.

OBJECTIVE: To examine the antibody responses of people with spinal cord injury (SCI) to the commercially available trivalent influenza vaccine. DESIGN: Prospective trial of patients and controls. SETTING: Veterans Affairs medical center. PARTICIPANTS: Forty people with SCI and 40 able-bodied subjects. INTERVENTION: Intramuscular administration of inactivated influenza vaccine. MAIN OUTCOME MEASURES: Antibody responses were determined by using the standard hemagglutination-inhibition test before and 4 weeks after vaccination. Serum antibody responses were assessed as follows: (1) percentage of each cohort achieving a 4-fold or greater rise in antibody titer, (2) percentage of each cohort achieving a postvaccination antibody titer of 32 or more, and (3) postvaccination geometric mean antibody titers. RESULTS: The serum antibody responses to each vaccine antigen were similar for the SCI and the control cohorts for the 3 outcomes. Neither the time since injury (</=1 y vs >1 y) nor the level of injury (paraplegia vs quadriplegia) affected the vaccine antibody responses in the SCI cohort. Subjects older than 65 years had lower postvaccination serum antibody levels than those younger than 65 years ( P <.05). CONCLUSIONS: People with SCI responded to influenza vaccination in a manner similar to able-bodied subjects and would be expected to benefit from vaccination.

Adult↗
PubMed2004

Immune response to influenza vaccination in children and adults with asthma: effect of corticosteroid therapy.

BACKGROUND: Annual influenza vaccination is currently recommended as a preventative measure for all patients with asthma. However, the effect of maintenance corticosteroid therapy on the immune response to influenza vaccine has received limited evaluation. OBJECTIVE: In this study, we evaluated the effect of corticosteroid therapy on the immune response to influenza vaccine in children and adults with asthma. METHODS: This was a substudy of a larger multicenter, randomized, double-masked, placebo-controlled, crossover study investigating the safety of trivalent influenza vaccine in patients with asthma. At baseline, 294 subjects were randomized to receive either placebo first (n=139) or inactivated trivalent split-virus influenza vaccine first (n=155). Study subjects were categorized into 2 groups: subjects in group 1 (n=148) were receiving medium-dose or high-dose inhaled corticosteroids (ICSs) or oral corticosteroids, whereas subjects in group 2 (n=146) were not receiving corticosteroids or were receiving low-dose ICSs. Serum hemagglutination inhibition antibody titers for the vaccine antigens were measured before and 4 weeks after the administration of placebo or vaccine. RESULTS: Serologic responses to each influenza vaccine antigen were significantly higher in vaccine than in placebo recipients and were similar among influenza vaccine recipients in groups 1 and 2 for the following endpoints: rise in antibody titer, percent of participants who developed a serological response, and percent of subjects who developed a serum hemagglutination inhibition antibody titer > or =1:32. Post hoc subgroup analyses demonstrated an attenuated response to influenza B antigen in subjects receiving high-dose ICS compared with subjects who were steroid-naïve (P<.05). CONCLUSION: The immune response to the A antigens of the inactivated influenza vaccine in subjects with asthma is not adversely affected by ICS therapy. High-dose ICS therapy may diminish the response to the B antigen of the vaccine, an observation that needs further investigation.

Adolescent↗