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Biomedical subjects

Larry J Anderson

Publications and source records attributed to Larry J Anderson.

At least 19 recordsLinked to original sources
PubMed2007

Recombinant protein-based assays for detection of antibodies to severe acute respiratory syndrome coronavirus spike and nucleocapsid proteins.

Recombinant severe acute respiratory syndrome (SARS) nucleocapsid and spike protein-based immunoglobulin G immunoassays were developed and evaluated. Our assays demonstrated high sensitivity and specificity to the SARS coronavirus in sera collected from patients as late as 2 years postonset of symptoms. These assays will be useful not only for routine SARS coronavirus diagnostics but also for epidemiological and antibody kinetic studies.

Antibodies, Viral↗
PubMed2007

Severe acute respiratory syndrome in children.

BACKGROUND: Severe acute respiratory syndrome (SARS) is a febrile, respiratory tract illness caused by infection with the newly identified SARS-associated coronavirus. A notable feature of the 2003 global SARS outbreak was the relative paucity of cases reported among children. We reviewed the epidemiologic and clinical features of SARS in children and discuss implications of these findings for diagnosis, treatment and prevention of SARS. METHODS: We performed a literature search to identify reports of pediatric (younger than 18 years of age) patients meeting the World Health Organization case definitions for SARS and abstracted relevant clinical and epidemiologic information. RESULTS: We identified 6 case series reporting 135 pediatric SARS patients (80 laboratory-confirmed, 27 probable and 28 suspect) from Canada, Hong Kong, Taiwan and Singapore. Among laboratory-confirmed and probable SARS cases, the most common symptoms included fever (98%), cough (60%) and nausea or vomiting (41%); 97% had radiographic abnormalities. The clinical presentation of SARS in patients older than 12 years of age was similar to that in adults. However, patients 12 years of age or younger had milder disease and were less likely than older children to be admitted to an intensive care unit, receive supplemental oxygen or be treated with methylprednisolone. No deaths were reported among children or adolescents with SARS, and at 6 months after illness only mild residual changes were reported in exercise tolerance and pulmonary function. There is only 1 published report of transmission of SARS virus from a pediatric patient. CONCLUSIONS: Children and adolescents are susceptible to SARS-associated coronavirus infection, although the clinical course and outcome are more favorable in children younger than 12 years of age compared with adolescents and adults. Transmission of SARS from pediatric patients appears to be uncommon but is possible.

Adolescent↗
PubMed2006

Prevalence of viral respiratory tract infections in children with asthma.

BACKGROUND: Previous studies support a strong association between viral respiratory tract infections and asthma exacerbations. The effect of newly discovered viruses on asthma control is less well defined. OBJECTIVE: We sought to determine the contribution of respiratory viruses to asthma exacerbations in children with a panel of PCR assays for common and newly discovered respiratory viruses. METHODS: Respiratory specimens from children aged 2 to 17 years with asthma exacerbations (case patients, n = 65) and with well-controlled asthma (control subjects, n = 77), frequency matched by age and season of enrollment, were tested for rhinoviruses, enteroviruses, respiratory syncytial virus, human metapneumovirus, coronaviruses 229E and OC43, parainfluenza viruses 1 to 3, influenza viruses, adenoviruses, and human bocavirus. RESULTS: Infection with respiratory viruses was associated with asthma exacerbations (63.1% in case patients vs 23.4% in control subjects; odds ratio, 5.6; 95% CI, 2.7- 11.6). Rhinovirus was by far the most prevalent virus (60% among case patients vs 18.2% among control subjects) and the only virus significantly associated with exacerbations (odds ratio, 6.8; 95% CI, 3.2-14.5). However, in children without clinically manifested viral respiratory tract illness, the prevalence of rhinovirus infection was similar in case patients (29.2%) versus control subjects (23.4%, P > .05). Other viruses detected included human metapneumovirus (4.6% in patients with acute asthma vs 2.6% in control subjects), enteroviruses (4.6% vs 0%), coronavirus 229E (0% vs 1.3%), and respiratory syncytial virus (1.5% vs 0%). CONCLUSION: Symptomatic rhinovirus infections are an important contributor to asthma exacerbations in children. CLINICAL IMPLICATIONS: These results support the need for therapies effective against rhinovirus as a means to decrease asthma exacerbations.

Adolescent↗
PubMed2006

Seasonal trends of human parainfluenza viral infections: United States, 1990-2004.

BACKGROUND: Human parainfluenza viruses (HPIVs) are important causes of upper and lower respiratory tract illness among children and adults. METHODS: We describe seasonal trends for individual HPIV serotypes and respiratory syncytial virus in the United States using data on the percentage of specimens with positive test results reported to the National Respiratory and Enteric Viruses Surveillance System during the period 1990-2004. Onset and conclusion dates for peaks in activity were determined with the Early Aberration Reporting System's cumulative sum method C2 by detecting periods when the number of positive HPIV test results was significantly greater than that observed for preceding weeks for each serotype. RESULTS: During the study period, increases in the percentage of positive HPIV-3 and HPIV-2 test results occurred annually during April-June and October-November, respectively. Increases in the percentage of positive HPIV-1 test results occurred biennially during September-December during odd-numbered years. During years when HPIV-1 was not circulating, more HPIV-3 activity was reported, either as a longer spring season or as a second smaller period of increased activity noted in the fall. Seasonal peaks in respiratory syncytial virus activity occurred annually during November-April. CONCLUSIONS: We provide a national perspective for HPIV activity during the 15-year study period and demonstrate distinct seasonal peaks in activity for HPIV-1, HPIV-2, and HPIV-3. In addition, our data suggest that there is an interaction between HPIV-3 and HPIV-1 activity, which may have implications in future prevention strategies.

Adult↗
PubMed2006

Respiratory syncytial virus G protein and G protein CX3C motif adversely affect CX3CR1+ T cell responses.

Interactions between fractalkine (CX3CL1) and its receptor, CX3CR1, mediate leukocyte adhesion, activation, and trafficking. The respiratory syncytial virus (RSV) G protein has a CX3C chemokine motif that can bind CX3CR1 and modify CXCL1-mediated responses. In this study, we show that expression of the RSV G protein or the G protein CX3C motif during infection is associated with reduced CX3CR1+ T cell trafficking to the lung, reduced frequencies of RSV-specific, MHC class I-restricted IFN-gamma-expressing cells, and lower numbers of IL-4- and CX3CL1-expressing cells. In addition, we show that CX3CR1+ cells constitute a major component of the cytotoxic response to RSV infection. These results suggest that G protein and the G protein CX3C motif reduce the antiviral T cell response to RSV infection.

Amino Acid Motifs↗
PubMed2006

Two outbreaks of severe respiratory disease in nursing homes associated with rhinovirus.

OBJECTIVES: To characterize illness and identify the etiology for two nursing home outbreaks of respiratory illness. DESIGN: Multisite outbreak investigations; cohort. SETTING: Two nursing homes in Pennsylvania. PARTICIPANTS: Facility A residents (n = 170), Facility B residents (n = 124), and employees (n = 91). MEASUREMENTS: Medical records for Facility A and B residents were reviewed, and employees from Facility B self-administered a questionnaire to identify risk factors for illness. Serological, oropharyngeal, and nasopharyngeal specimens were collected for both outbreaks, and testing for respiratory pathogens was performed. RESULTS: In Facility A, 40 (24%) of 170 residents were identified with respiratory illness; 13 (33%) case-patients had radiographically confirmed pneumonia, 15 (38%) were taken to a hospital, and two (5%) died. Of 10 specimens collected from symptomatic Facility A case-patients, four (40%) tested positive using reverse transcription polymerase chain reaction for rhinovirus. In Facility B, 77 (62%) of 124 residents had respiratory illness, and 40 (52%) had radiographically confirmed pneumonia; 12 (16%) case-patients were hospitalized, and five (6%) died. Of 19 respiratory specimens collected from symptomatic Facility B case-patients, six (32%) were positive for rhinovirus; one was from an employee. Five (50%) of 10 rhinovirus-positive cases in both outbreaks had clinical and radiographic evidence of pneumonia. CONCLUSION: These investigations suggest that rhinoviruses may be an underrecognized cause of respiratory outbreaks in nursing homes, capable of causing pneumonia and perhaps death.

Acute Disease↗
PubMed2005

Trends in hospitalizations for pneumonia among persons aged 65 years or older in the United States, 1988-2002.

CONTEXT: Pneumonia causes significant mortality and morbidity among persons aged 65 years or older. However, few studies have explored trends according to age groups, which may affect intervention strategies. OBJECTIVES: To examine trends in hospitalizations for pneumonia among persons aged 65 years or older and to compare characteristics, outcomes, and comorbid diagnoses. DESIGN, SETTING, AND PATIENTS: Data from 1988 through 2002 on pneumonia and comorbid diagnoses among patients aged 65 to 74 years, 75 to 84 years, and 85 years or older from the National Hospital Discharge Survey. MAIN OUTCOME MEASURES: Hospitalization rates by first-listed and any-listed discharge codes for pneumonia; proportions of hospitalizations reporting comorbid diagnoses for the 3 age groups (65-74 years, 75-84 years, > or =85 years). RESULTS: Hospitalization rates by both first-listed and any-listed discharge codes for pneumonia increased by 20% from 1988-1990 to 2000-2002 for patients aged 65 to 74 years (P = .01) and for patients aged 75 to 84 years (P<.001). Rates of hospitalization for pneumonia were 2-fold higher for patients aged 85 years or older (51 per 1000 population for first-listed discharge code of pneumonia; 95% confidence interval [CI], 46-55 per 1000 population) than among patients aged 75 to 84 years (26 per 1000 population; 95% CI, 24-28 per 1000 population), but did not significantly increase from 1988-1990 to 2000-2002. The proportion of patients aged 65 years or older diagnosed with pneumonia and a chronic cardiac disease, chronic pulmonary disease, or diabetes mellitus increased from 66% (SE, 1.0%) in 1988-1990 to 77% (SE, 0.8%) in 2000-2002. The risk of death during a hospitalization for pneumonia compared with the risk of death during a hospital stay for the 10 other most frequent causes of hospitalization was 1.5 (95% CI, 1.4-1.7) and remained constant from 1988-1990 to 2000-2002. CONCLUSIONS: Hospitalization rates for pneumonia have increased among US adults aged 64 to 74 years and aged 75 to 84 years during the past 15 years. Among those aged 85 years or older, at least 1 in 20 patients were hospitalized each year due to pneumonia. Concomitantly, the proportion of comorbid chronic diseases has increased. Efforts to prevent pneumonia should include reducing preventable comorbid conditions and improving vaccine effectiveness and vaccination programs in elderly persons.

Aged↗
PubMed2005

Monoclonal antibodies to SARS-associated coronavirus (SARS-CoV): identification of neutralizing and antibodies reactive to S, N, M and E viral proteins.

Monoclonal antibodies (Mabs) against the Urbani strain of the SARS-associated coronavirus (SARS-CoV) were developed and characterized for reactivity to SARS-CoV and SARS-CoV S, N, M, and E proteins using enzyme-linked immunoabsorbent (ELISA), radioimmunoprecipitation, immunofluorescence, Western Blot and microneutralization assays. Twenty-six mAbs were reactive to SARS-CoV by ELISA, and nine were chosen for detailed characterization. Five mAbs reacted against the S protein, two against the M protein, and one each against the N and E proteins. Two of five S protein mAbs neutralized SARS-CoV infection of Vero E6 cells and reacted to an epitope within amino acids 490-510 in the S protein. While two of the three non-neutralizing antibodies recognized at second epitope within amino acids 270-350. The mAbs characterized should prove useful for developing SARS-CoV diagnostic assays and for studying the biology of infection and pathogenesis of disease.

Animals↗
PubMed2005

SARS-coronavirus replication in human peripheral monocytes/macrophages.

A novel coronavirus (CoV) has been described in association with cases of severe acute respiratory syndrome (SARS). The virus, SARS-CoV, differs from the previously described human coronaviruses, 229E and OC43. 229E was previously shown to productively infect human monocytes/macrophages, whereas OC43 poorly infected the cells. In this study, we examined whether SARS-CoV could productively infect purified monocytes/macrophages (PM) derived from human donor cells. Unlike 229E-infected cells, which produced viral titers of 10(3.5) to 10(6)TCID50/ml, SARS-CoV replicated poorly in PM, producing titers of 10(1.75) to 10(2)TCID50/ml. This finding was similar to results reported for OC43-infected cells, with titers ranging from 10(1.2) to 10(2.7)TCID50/ml. Of interest, SARS-CoV proteins were detected only in PM that did not produce significant amounts of interferon (IFN)-alpha, and in one such case, preliminary electron microscope studies demonstrated that SARS-CoV-like particles could enter the cells, possibly via phagocytosis. These results suggest that SARS-CoV, like human CoV OC43, poorly infects human PM, and production of IFN-alpha by these cells further limits the infection. Given the importance of monocytes/macrophages to the immune response, it is possible that their infection by SARS-CoV and alteration of this infection by IFN-alpha may be important to the course of the infection in humans.

Adult↗
PubMed2005

Lower respiratory tract infections among american Indian and Alaska Native children and the general population of U.S. Children.

BACKGROUND AND OBJECTIVE: Lower respiratory tract infections (LRTIs) cause substantial childhood morbidity. This study characterizes and compares LRTI-associated morbidity among American Indian/Alaska Native (AI/AN) children and the general population of U.S. children. METHODS: Hospitalization and outpatient records with a diagnosis indicating LRTIs were evaluated for children aged younger than 5 years during 1990-2001. RESULTS: For 1999-2001, the LRTI-associated hospitalization rate was significantly higher for AI/AN children than for U.S. children (116.1 versus 63.2/1000, respectively), with the disparity being greater for infants than for 1- to 4-year-old children. Also the rate of LRTI-associated outpatient visits among AI/AN infants was higher than that for all U.S. infants (737.7 versus 207.2/1000, respectively). LRTI hospitalization and outpatient visit rates were highest in the Alaska and Southwest Indian Health Service regions. During 1990-2001, the LRTI hospitalization rate among AI/AN infants in the Alaska region and among the general U.S. infant population increased. Bronchiolitis-associated hospitalization rates increased for AI/AN and U.S. infants, whereas the pneumonia-associated hospitalization rate decreased among AI/AN infants and remained stable among U.S. infants. CONCLUSIONS: LRTIs continue to be an important cause of morbidity in children, especially among AI/AN infants in the Alaska and Southwest regions. Strategies to reduce LRTI hospitalizations and outpatient visits are warranted for all infants, but the greatest potential impact would be among AI/AN infants.

Age Distribution↗
PubMed2005

Real-time detection of virus particles and viral protein expression with two-color nanoparticle probes.

Respiratory syncytial virus (RSV) mediates serious lower respiratory tract illness in infants and young children and is a significant pathogen of the elderly and immune compromised. Rapid and sensitive RSV diagnosis is important to infection control and efforts to develop antiviral drugs. Current RSV detection methods are limited by sensitivity and/or time required for detection. In this study, we show that antibody-conjugated nanoparticles rapidly and sensitively detect RSV and estimate relative levels of surface protein expression. A major development is use of dual-color quantum dots or fluorescence energy transfer nanobeads that can be simultaneously excited with a single light source.

Respiratory Syncytial Viruses↗
PubMed2004

Direct sequencing of SARS-coronavirus S and N genes from clinical specimens shows limited variation.

Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) emerged, in November 2002, as a novel agent causing severe respiratory illness. To study sequence variation in the SARS-CoV genome, we determined the nucleic acid sequence of the S and N genes directly from clinical specimens from 10 patients--1 specimen with no matched SARS-CoV isolate, from 2 patients; multiple specimens from 3 patients; and matched clinical-specimen/cell-culture-isolate pairs from 6 patients. We identified 3 nucleotide substitutions that were most likely due to natural variation and 2 substitutions that arose after cell-culture passage of the virus. These data demonstrate the overall stability of the S and N genes of SARS-CoV over 3 months during which a minimum of 4 generations for transmission events occurred. These findings are a part of the expanding investigation of the evolution of how this virus adapts to a new host.

Amino Acid Substitution↗
PubMed2004

Severe acute respiratory syndrome coronavirus on hospital surfaces.

BACKGROUND: Health care workers continued to contract severe acute respiratory syndrome (SARS), even after barrier precautions were widely implemented. METHODS: We explored the possible contribution of contaminated hospital surfaces to SARS transmission by swabbing surfaces in 2 hospitals and testing the swab samples by reverse-transcriptase polymerase chain reaction (RT-PCR) and viral culture. RESULTS: Twenty-six of 94 swab samples tested positive for viral RNA. Swab samples of respiratory secretions from each of the 4 patients examined tested positive by RT-PCR, as were 12 of 43 swabs from patient rooms and 10 of 47 swabs from other parts of the hospital, including the computer mouses at 2 nursing stations and the handrail of the public elevator. Specimens from areas with patients with SARS in the most infectious phase of illness (days 5-15 after onset) were more likely to be RNA positive than were swab specimens from elsewhere (24 of 63 samples vs. 2 of 31 samples; P=.001). All cultures showed no growth. CONCLUSIONS: Although the viruses identified may have been noninfectious, health care workers should be aware that SARS coronavirus can contaminate environmental surfaces in the hospital, and fomites should be considered to be a possible mode of transmission of SARS.

Communicable Disease Control↗
PubMed2004

Pulmonary delivery of respiratory syncytial virus DNA vaccines using macroaggregated albumin particles.

At present there is no safe and effective vaccine for respiratory syncytial virus (RSV). DNA vaccines encoding RSV surface glycoproteins are one option being examined. Current methods to deliver DNA vaccines generally require repeated high dose intramuscular or intradermal administration for effectiveness. In this study, we examine the efficacy of pulmonary DNA vaccination using low dose DNA vaccines encoding the RSV F glycoprotein conjugated to macroaggregated albumin (MAA-F). Single vaccination of BALB/c mice with 1 microg MAA-F was ineffective, however mice boosted with an additional 1 microg MAA-F, or vaccinated a single time with 10 microg MAA-F, developed substantially improved immunity associated with reduced viral titers, increased anti-F antibody responses, and enhanced Th1 and Th2 intracellular cytokine responses. This study shows that MAA may be a useful carrier for RSV DNA vaccines.

Administration, Intranasal↗
PubMed2004

Guidelines for preventing health-care--associated pneumonia, 2003: recommendations of CDC and the Healthcare Infection Control Practices Advisory Committee.

This report updates, expands, and replaces the previously published CDC "Guideline for Prevention of Nosocomial Pneumonia". The new guidelines are designed to reduce the incidence of pneumonia and other severe, acute lower respiratory tract infections in acute-care hospitals and in other health-care settings (e.g., ambulatory and long-term care institutions) and other facilities where health care is provided. Among the changes in the recommendations to prevent bacterial pneumonia, especially ventilator-associated pneumonia, are the preferential use of oro-tracheal rather than naso-tracheal tubes in patients who receive mechanically assisted ventilation, the use of noninvasive ventilation to reduce the need for and duration of endotracheal intubation, changing the breathing circuits of ventilators when they malfunction or are visibly contaminated, and (when feasible) the use of an endotracheal tube with a dorsal lumen to allow drainage of respiratory secretions; no recommendations were made about the use of sucralfate, histamine-2 receptor antagonists, or antacids for stress-bleeding prophylaxis. For prevention of health-care--associated Legionnaires disease, the changes include maintaining potable hot water at temperatures not suitable for amplification of Legionella spp., considering routine culturing of water samples from the potable water system of a facility's organ-transplant unit when it is done as part of the facility's comprehensive program to prevent and control health-care--associated Legionnaires disease, and initiating an investigation for the source of Legionella spp. when one definite or one possible case of laboratory-confirmed health-care--associated Legionnaires disease is identified in an inpatient hemopoietic stem-cell transplant (HSCT) recipient or in two or more HSCT recipients who had visited an outpatient HSCT unit during all or part of the 2-10 day period before illness onset. In the section on aspergillosis, the revised recommendations include the use of a room with high-efficiency particulate air filters rather than laminar airflow as the protective environment for allogeneic HSCT recipients and the use of high-efficiency respiratory-protection devices (e.g., N95 respirators) by severely immunocompromised patients when they leave their rooms when dust-generating activities are ongoing in the facility. In the respiratory syncytial virus (RSV) section, the new recommendation is to determine, on a case-by-case basis, whether to administer monoclonal antibody (palivizumab) to certain infants and children aged <24 months who were born prematurely and are at high risk for RSV infection. In the section on influenza, the new recommendations include the addition of oseltamivir (to amantadine and rimantadine) for prophylaxis of all patients without influenza illness and oseltamivir and zanamivir (to amantadine and rimantadine) as treatment for patients who are acutely ill with influenza in a unit where an influenza outbreak is recognized. In addition to the revised recommendations, the guideline contains new sections on pertussis and lower respiratory tract infections caused by adenovirus and human parainfluenza viruses and refers readers to the source of updated information about prevention and control of severe acute respiratory syndrome.

Adenovirus Infections, Human↗
PubMed2004

Potent neutralization of severe acute respiratory syndrome (SARS) coronavirus by a human mAb to S1 protein that blocks receptor association.

Effective prophylaxis and antiviral therapies are urgently needed in the event of reemergence of the highly contagious and often fatal severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) infection. We have identified eight recombinant human single-chain variable region fragments (scFvs) against the S1 domain of spike (S) protein of the SARS-CoV from two nonimmune human antibody libraries. One scFv 80R efficiently neutralized SARS-CoV and inhibited syncytia formation between cells expressing the S protein and those expressing the SARS-CoV receptor angiotensin-converting enzyme 2 (ACE2). Mapping of the 80R epitope showed it is located within the N-terminal 261-672 amino acids of S protein and is not glycosylation-dependent. 80R scFv competed with soluble ACE2 for association with the S1 domain and bound S1 with high affinity (equilibrium dissociation constant, Kd=32.3 nM). A human IgG1 form of 80R bound S1 with a 20-fold higher affinity of 1.59 nM comparable to that of ACE2 (Kd=1.70 nM), and neutralized virus 20-fold more efficiently than the 80R scFv. These data suggest that the 80R human monoclonal antibody may be a useful viral entry inhibitor for the emergency prophylaxis and treatment of SARS, and that the ACE2-binding site of S1 could be an attractive target for subunit vaccine and drug development.

Amino Acid Sequence↗