Biomedical subjects

Larry J Anderson

Publications and source records attributed to Larry J Anderson.

53 records · Page 3Linked to original sources

PubMed2003

Sequence analysis of the N, P, M and F genes of Canadian human metapneumovirus strains.

The complete nucleotide sequences of the nucleoprotein (N), phosphoprotein (P), matrix protein (M), and fusion protein (F) genes of 15 Canadian human metapneumovirus (hMPV) isolates were determined. Phylogenetic analysis revealed two distinct genetic clusters, or groups for each gene with additional sequence variability within the individual groups. Comparison of the deduced amino acid sequences for the N, M and F genes of the different isolates revealed that all three genes were well conserved with 94.1-97.6% identity between the two distinct clusters The P gene showed more diversity with 81.6-85.7% amino acid identity for isolates between the two clusters, and 94.6-100% for isolates within the same cluster.

Amino Acid Sequence↗

PubMed2003

Risk factors for bronchiolitis-associated deaths among infants in the United States.

BACKGROUND: Risk factors for bronchiolitis deaths have not been described on a national level. We examined the epidemiology of and identified risk factors for bronchiolitis-associated deaths among infants in the United States. METHODS: Multiple cause-of-death and linked birth/infant death data for 1996 through 1998 were used to examine bronchiolitis-associated infant deaths. Risk factors were assessed by comparing infants who died with bronchiolitis and surviving infants. RESULTS: During 1996 through 1998 there were 229 bronchiolitis infant deaths, resulting in an average annual infant mortality rate of 2.0 per 100 000 live births. The majority (55%) of infant deaths occurred among infants ages 1 through 3 months. The bronchiolitis mortality rate was highest among infants weighing <1500 g at birth (VLBW) as compared with infants weighing 1500 to 2499 g (LBW) and > or =2500 g at birth (29.8, 6.4 and 1.3 per 100 000 live births, respectively). Sixty-three percent of bronchiolitis deaths were among infants weighing > or =2500 g. VLBW and LBW infants remained at an increased risk of dying with bronchiolitis after controlling for other risk factors. Other risk factors included increasing birth order, low 5-min Apgar score, young maternal age, unmarried mother and tobacco use during pregnancy. CONCLUSIONS: VLBW and LBW infants are at increased risk of dying with bronchiolitis, even when taking into account other risk factors. Although infants weighing <2500 g at birth are at increased risk for dying with bronchiolitis, the majority of bronchiolitis deaths occur among infants of normal birth weight.

Bronchiolitis↗

PubMed2003

Substantial variability in community respiratory syncytial virus season timing.

BACKGROUND: Respiratory syncytial virus (RSV) is the major cause of bronchiolitis and pneumonia in young children. Prevention of RSV disease in children in certain high risk groups through use of immunoglobulin preparations has been recommended by the American Academy of Pediatrics since 1998. A more precise understanding of the timing of annual RSV epidemics should assist providers in maximizing the benefit of these preventive therapies. The objective of this study was to determine whether current national RSV surveillance data could be used to define the timing of seasonal outbreaks METHODS: Weekly RSV testing data from the National Respiratory and Enteric Viruses Surveillance System for the period July 1990 through June 2000 were analyzed. RSV season onset week, peak week and duration were calculated for the entire United States, Census regions and select local laboratories. Season variability was estimated by comparing calculations for individual RSV seasons to median measurements for the entire surveillance period RESULTS: RSV seasons in the South region began significantly earlier (P < 0.05) and lasted longer (P < 0.05) than seasons for the rest of the nation. RSV seasons in the Midwest region began significantly later (P < 0.01) and were shorter (P < 0.05) than those for the rest of the nation. Local RSV seasons varied substantially by year and by laboratory. The variability between laboratories generally increased with distance between laboratories CONCLUSIONS: Onset weeks and durations of RSV seasons vary substantially by year and location. Local RSV data are needed to accurately define the onset and offset of RSV seasons and to refine timing of passive immune prophylaxis therapy recommendations.

Age Distribution↗

PubMed2003

GeneScan reverse transcription-PCR assay for detection of six common respiratory viruses in young children hospitalized with acute respiratory illness.

A reverse transcription-PCR (RT-PCR) assay based on automated fluorescent capillary electrophoresis and GeneScan software analysis was developed to detect six common respiratory viruses in clinical specimens from young children. Assays for human respiratory syncytial virus (HRSV); human parainfluenza viruses 1, 2, and 3 (HPIV1, -2, and -3, respectively); and influenza A and B viruses were incorporated into a single standard assay format. The optimized assay panel was used to test 470 respiratory specimens obtained from 462 children hospitalized with acute respiratory illness that had been previously tested by viral culture (405 specimens) or direct immunofluorescence staining (DIF) (65 specimens). Of 93 specimens positive for respiratory viruses by culture or DIF, 86 (92%) were positive by RT-PCR, including 66 HRSV, 2 HPIV2, 5 HPIV3, 3 influenza A virus, and 10 influenza B virus specimens. An additional 119 respiratory viruses were identified by RT-PCR in 116 patients for whom results were negative by viral isolation or DIF. We conclude that the GeneScan RT-PCR panel can markedly improve detection of acute respiratory virus infections in young children.

Acute Disease↗

PubMed2003

The G glycoprotein of respiratory syncytial virus depresses respiratory rates through the CX3C motif and substance P.

Respiratory syncytial virus (RSV) infection in the neonate can alter respiratory rates, i.e., lead to episodes of apnea. We show that RSV G glycoprotein reduces respiratory rates associated with the induction of substance P (SP) and G glycoprotein-CX3CR1 interaction, an effect that is inhibited by treatment with anti-G glycoprotein, anti-SP, or anti-CX3CR1 monoclonal antibodies. These data suggest new approaches for treating some aspects of RSV disease.

Animals↗

PubMed2003

Enhanced disease and pulmonary eosinophilia associated with formalin-inactivated respiratory syncytial virus vaccination are linked to G glycoprotein CX3C-CX3CR1 interaction and expression of substance P.

Vaccination with formalin-inactivated respiratory syncytial virus (FI-RSV) vaccine or RSV G glycoprotein results in enhanced pulmonary disease after live RSV infection. Enhanced pulmonary disease is characterized by pulmonary eosinophilia and is associated with a substantial inflammatory response. We show that the absence of the G glycoprotein or G glycoprotein CX3C motif during FI-RSV vaccination or RSV challenge of FI-RSV-vaccinated mice, or treatment with anti-substance P or anti-CX3CR1 antibodies, reduces or eliminates enhanced pulmonary disease, modifies T-cell receptor Vbeta usage, and alters CC and CXC chemokine expression. These data suggest that the G glycoprotein, and in particular the G glycoprotein CX3C motif, is key in the enhanced inflammatory response to FI-RSV vaccination, possibly through the induction of substance P.

Amino Acid Motifs↗

PubMed2003

Infectious disease hospitalizations among American Indian and Alaska native infants.

OBJECTIVE: To describe the burden and trends in hospitalizations associated with infectious diseases among American Indian and Alaska Native (AI/AN) infants. METHODS: First-listed infectious disease hospitalizations and hospitalization rates among AI/AN infants and infants in the general US population from 1988-1999 were analyzed by using Indian Health Service/tribal hospital discharge data and the National Hospital Discharge Survey data, respectively. RESULTS: Infectious disease hospitalizations accounted for 53% of all AI/AN infant hospitalizations and approximately 43% of all US infant hospitalizations during 1988-1999. The annual hospitalization rate for infectious diseases among AI/AN infants declined from 27,486 per 100,000 infants in 1988 to 14,178 per 100,000 infants in 1999. However, the rates for AI/AN infants within the Alaska, Southwest, and Northern Plains regions remained higher than that for the general US infant population at the end of the study period. Lower respiratory tract infection hospitalizations accounted for almost 75% of AI/AN infant infectious disease hospitalizations, and the lower respiratory tract infection hospitalization rate for AI/AN infants was twice that for US infants. CONCLUSIONS: Although infectious disease hospitalization rates for AI/AN infants have declined, AI/AN infants continue to have a higher infectious disease burden than the general US infant population.

Age Factors↗

PubMed2002

Virological features and clinical manifestations associated with human metapneumovirus: a new paramyxovirus responsible for acute respiratory-tract infections in all age groups.

The virological features and clinical findings associated with the new human metapneumovirus (HMPV) were examined retrospectively in Canadian patients hospitalized for various respiratory conditions since 1993. Thirty-eight previously unidentified respiratory viruses isolated from rhesus monkey kindey (LLC-MK2) cells were found to be positive for HMPV by reverse-transcription polymerase chain reaction, and those strains clustered in 2 phylogenetic groups. Children aged <5 years and elderly subjects aged >65 years represented 35.1% and 45.9% of the HMPV-infected cases, respectively. In hospitalized children, the most frequent diagnoses were pneumonitis (66.7%) and bronchiolitis (58.3%), whereas bronchitis and/or bronchospasm (60%) and pneumonitis (40%) were most commonly seen in elderly subjects. Of the 15 patients with pneumonitis, 4 (26.7%) had immunosuppressive conditions and 6 (40%) were infants aged <15 months. These findings suggest that HMPV can be associated with severe lower-respiratory-tract infections in very young children, the elderly, and immunocompromised patients.

Acute Disease↗

PubMed2002

Burden of encephalitis-associated hospitalizations in the United States, 1988-1997.

Analysis of the National Hospital Discharge Survey data for 1988-1997 revealed a substantial disease burden associated with encephalitis in the United States: on average, there were nearly 19,000 hospitalizations (7.3 hospitalizations per 100,000 population), 230,000 hospital days, and 1400 deaths annually. For most encephalitis-associated hospitalizations (59.5%), the etiologic agent was unknown or not recorded; the most common etiologic categories among known causes were "viral" (38.2%) and "other infectious" (34.1%). The most common individual diagnoses with known agents were herpetic and toxoplasmic encephalitides (each associated with an annual average of 2100 hospitalizations). Human immunodeficiency virus infection was listed among discharge diagnoses for 15.6% of hospitalizations. Rates of encephalitis-associated hospitalization were highest for children <1 year old and persons > or =65 years old. The etiology of encephalitis was unknown for persons > or =65 years old significantly more often than it was for younger persons. The average cost of an encephalitis-associated hospitalization, as determined by the Healthcare Cost and Utilization Project for 1997, was $28,151, for an annual national cost of hospitalization of $650 million.

Adolescent↗

PubMed2002

Characterization of human metapneumoviruses isolated from patients in North America.

Human metapneumovirus (HMPV) was recently identified in The Netherlands and was linked to acute respiratory tract illness. In this study, 11 isolates from 10 patients with respiratory disease from Quebec, Canada, were tested by a reverse-transcriptase polymerase chain reaction based on the fusion protein gene. Identified sequences were consistent with HMPV. The patients were 2 months to 87 years of age (median age, 58 years) and presented with acute respiratory tract illness during the winter season. Sequence studies of the nucleocapsid, fusion, and polymerase genes identified 2 main lineages of HMPV and cocirculation of both lineages during the same year. These findings support a previous finding that HMPV is a human respiratory pathogen that merits further study.

Adolescent↗

PubMed2002

Peripheral blood mononuclear cells from infants hospitalized because of respiratory syncytial virus infection express T helper-1 and T helper-2 cytokines and CC chemokine messenger RNA.

The cellular immune response to respiratory syncytial virus (RSV) infection was examined in infants aged 1-21 months who were hospitalized because of RSV infection or non-RSV-related illness. RSV- or control-stimulated peripheral blood mononuclear cells were examined to determine RSV-specific intracellular T helper-1 (Th1) and T helper- 2 (Th2) cytokine expression, chemokine messenger RNA (mRNA) expression, and cell surface markers. Patients hospitalized because of RSV infection had increased numbers of CD16(+) and CD56(bright) cells and had RSV-specific increases in Th1 (interleukin [IL]-2 and interferon-gamma) and Th2 (IL-4 and IL-6) cytokines and CC chemokines (macrophage inflammatory protein [MIP]-1alpha, MIP-1beta, and RANTES [regulated on activation, normally T cell expressed and secreted]) mRNA expression. The results suggest that RSV infection induces both Th1 and Th2 cytokine expression and CC chemokine expression.

Chemokine CCL3↗

PubMed2002

Substance P receptor expression on lymphocytes is associated with the immune response to respiratory syncytial virus infection.

The kinetics and magnitude of SP receptor expression was determined for bronchoalveolar leukocyte cell subsets from BALB/c mice in the primary immune response to respiratory syncytial virus (RSV) and human parainfluenza virus-3 (PIV3) infection, and in the secondary immune response to RSV and PIV3 challenge. In both the primary and secondary responses to infection, expression of substance P (SP) receptors was markedly increased by infection, especially for T lymphocytes, compared to B220+, CD11b+ and CD14+ cells. CD4+ T lymphocytes predominantly expressed SP receptors in the secondary response. These results suggest that SP receptor expression may be important in the development of primary and secondary immune responses to respiratory virus infections.

Animals↗

PubMed2002

Multiplex assay for detection of strain-specific antibodies against the two variable regions of the G protein of respiratory syncytial virus.

The role of strain differences in respiratory syncytial virus (RSV) disease has not been clearly defined. To investigate the possibility that strain differences contribute to susceptibility to repeat infections, we developed assays to detect antibodies to the two variable regions of the RSV G protein by cloning and expressing the internal variable region at amino acids (aa) 60 to 172 (g1) and the carboxy-terminal variable region at aa 193 to the carboxy terminus (g2) from different genotypes of RSV. The purified proteins were covalently linked to beads with different proportions of red and orange fluorescent dyes and reacted against serum specimens. Antibody reacting against the differently colored beads, and thus against different G polypeptides, was detected by use of flow cytometry and the Luminex system. This assay system detected group- and, to some extent, genotype-specific responses to RSV infection and can be used to investigate the role of strain differences in RSV disease.

Animals↗

PubMed2002

Neutralizing anti-F glycoprotein and anti-substance P antibody treatment effectively reduces infection and inflammation associated with respiratory syncytial virus infection.

Respiratory syncytial virus (RSV) is the most important virus mediating lower respiratory tract illness in infants and young children. RSV infection is associated with pulmonary inflammation and increased levels of substance P (SP), making the airways and leukocytes that express SP receptors susceptible to the proinflammatory effects of this peptide. This study examines combining neutralizing anti-F glycoprotein and anti-SP antibody treatment of RSV-infected BALB/c mice to inhibit RSV replication and inflammation associated with infection. BALB/c mice were prophylactically treated with antibody prior to RSV infection or were therapeutically treated at day 2 or 6 post-RSV infection. Prophylactic or therapeutic treatment with anti-SP antibodies promptly reduced pulmonary inflammatory cell infiltration and decreased the number of cells expressing proinflammatory cytokines, while anti-F antibody treatment reduced virus titers. The results suggest that combined anti-viral and anti-SP antibody treatment may be effective in treating RSV disease.

Animals↗

PubMed2002

Outpatient and hospital visits associated with otitis media among American Indian and Alaska native children younger than 5 years.

OBJECTIVE: To describe the burden of otitis media (OM) among American Indian and Alaska Native (AI/AN) children. METHODS: OM morbidity among AI/AN younger than 5 years was evaluated using OM-associated outpatient visit and hospitalization rates. These rates were compared with outpatient and hospitalization rates for the general US population of children younger than 5 years. AI/AN children who were younger than 5 years and receiving care through the Indian Health Service or tribally operated facilities and US children younger than 5 years of age were studied. RESULTS: From 1994--1996, the average annual rate of AI/AN OM-associated outpatient visits was 138 per 100 children younger than 5 years. Among AI/AN children younger than 1 year (infants), these rates were almost 3 times greater than those for US infants (318 vs 110 visits per 100 infants, respectively). AI/AN children 1 to 4 years of age had rates 1.5 times greater than US children of the same age (107 vs 65 visits per 100 children, respectively). AI/AN children also experienced higher rates of OM-associated hospitalization than did US children (5643 vs 2440 per 100 000 infants, 823 vs 665 per 100 000 1- to 4-year-olds). CONCLUSION: We found that AI/AN children, especially AI/AN infants, have higher OM-associated outpatient and hospitalization rates than those for the general US population of children. The disparity in rates suggests that additional prevention programs and continued resources are needed to reduce OM morbidity among AI/AN children.

Alaska↗

PubMed2002

Molecular epidemiology of adenovirus type 7 in the United States, 1966-2000.

Genetic variation among 166 isolates of human adenovirus 7 (Ad7) obtained from 1966 to 2000 from the United States and Eastern Ontario, Canada, was determined by genome restriction analysis. Most (65%) isolates were identified as Ad7b. Two genome types previously undocumented in North America were also identified: Ad7d2 (28%), which first appeared in 1993 and was later identified throughout the Midwest and Northeast of the United States and in Canada; and Ad7h (2%), which was identified only in the U.S. Southwest in 1998 and 2000. Since 1996, Ad7d2 has been responsible for several civilian outbreaks of Ad7 disease and was the primary cause of a large outbreak of respiratory illness at a military recruit training center. The appearance of Ad7d2 and Ad7h in North America represents recent introduction of these viruses from previously geographically restricted areas and may herald a shift in predominant genome type circulating in the United States.

Adenovirus Infections, Human↗

PubMedDate not supplied

Viral meningitis-associated hospitalizations in the United States, 1988-1999.

We used the National Hospital Discharge Survey and the Nationwide Inpatient Sample of the Health Care Cost and Utilization Project to estimate disease burden associated with viral meningitis hospitalizations in the United States. During 1988-1999, viral meningitis accounted for an estimated 434,000 hospitalizations (annual average, 36,000; average annual hospitalization rate, 14/100,000), and 2.1 million hospital days (annual average, 175,000). The estimated mean charge for viral meningitis-associated hospitalization during 1993-1997 varied between USD 6,562 and 8,313, resulting in annual estimated hospitalization costs between USD 234 and 310 million and a total estimated cost of nearly USD 1.3 billion for the 5-year period. In summary, viral meningitis remains an important cause of morbidity and financial burden and merits efforts to improve diagnostic, treatment, and prevention options.

Adolescent↗