A truncated ORF2 protein contains the most immunogenic site on ORF2: antibody responses to non-vaccine sequences following challenge of vaccinated and non-vaccinated macaques with hepatitis E virus

A candidate hepatitis E vaccine is composed of amino acids (aa) 112-607 of the 660-aa protein encoded by open reading frame 2 (ORF2) of hepatitis E virus (HEV). We have studied the antibody response to vaccine-associated epitopes and to epitopes excluded from the vaccine to determine if important epitopes were omitted from the vaccine and if antibody responses to these regions could be used to differentiate between infection and vaccination. ELISAs were developed based on genotype 1 ORF2 peptides, containing aa 112-607 (vaccine), 458-607 (minimum neutralization site), 1-111 (N-terminus) and 607-660 (C-terminus), as well as on ORF3 peptides, containing aa 1-123 (complete) and 91-123 (C-terminus). All naive macaques infected with HEV genotype 1, 2, 3 or 4 produced antibodies to all ORF2 peptides. Anti-ORF3 was detected in both monkeys infected with genotype 1 virus and in one of two infected with genotype 2 virus. These antibody responses were considerably weaker than those directed against the neutralization site. In contrast, vaccinated animals that were challenged with HEV had a diminished or absent immune response to the peptides not included in the vaccine. Thus, only minor epitopes were excluded from the vaccine; they had limited utility for distinguishing between vaccination and infection.     

Third Component, HBeAg/3, of Hepatitis B e Antigen System, Identified by Three Different Double-Diffusion Techniques

A third component, HB(e)AG/3, of the hepatitis B e antigen system has been detected, and it was consistently detected in three variations of the double-diffusion technique.     

Tarsal navicular stress fractures: radiographic evaluation

Tarsal navicular stress fractures are a potential source of disabling foot pain in physically active individuals. The diagnosis of tarsal navicular stress fracture requires a high index of clinical and radiographic suspicion because the fracture is only rarely evident on routine radiographs or standard tomograms. The radiographic diagnosis of a tarsal navicular stress fracture may require anatomic anteroposterior tomograms or a radionuclide bone scan with plantar views. Radiographic examinations of 23 fractures in 21 patients are evaluated.     

Epidemic of community-acquired methicillin-resistant Staphylococcus aureus infections: a 14-year study at Driscoll Children's Hospital

BACKGROUND: Previously we reported the rapid emergence and exponential increase of community-acquired (CA) methicillin-resistant Staphylococcus aureus (MRSA) infections in South Texas children. OBJECTIVE: To assess whether changes have occurred in the frequency, types, susceptibility, and treatment of CAMRSA infections at Driscoll Children's Hospital. METHODS: Data from 1990 through 2001 were collected during 2 previous studies. Data from 2002 through 2003 were collected and compared with data from 1990 through 2001. All S aureus isolates were identified by a computer-assisted search of culture results, and the medical records were reviewed for all patients with MRSA infections. RESULTS: A total of 1002 MRSA cases were identified from 1990 through 2003 of which 928 (93%) were community-acquired. The number of CAMRSA cases ranged from 0 to 9 per year from 1990 through 1999 and then increased exponentially from 36 in 2000 to 459 in 2003. The most common type of CAMRSA infection in children without (94%) and with (72%) risk factors was cellulitis and abscess. A higher percentage of children with risk factors had invasive CAMRSA infections (26% vs 3%; P<.001). From 2002 through 2003, there was a significant difference in clindamycin susceptibility between CAMRSA isolates from children without and with risk factors and nosocomial isolates (97% and 86% vs 62%; P<.005). A higher percentage of patients admitted for treatment of CAMRSA infections received an empirical intravenous antibiotic to which the organism was susceptible when comparing 2002-2003 with 1990-2000 (96% vs 15%; P<.001). During this 14-year study, all patients recovered, including those with life-threatening CAMRSA infections. CONCLUSION: The rapid emergence of CAMRSA as a cause of noninvasive and invasive infections in children, which started occurring in the 1990s, has reached epidemic proportions.     

Driscoll Children's Hospital respiratory syncytial virus database: risk factors, treatment and hospital course in 3308 infants and young children, 1991 to 2002

BACKGROUND: Treatment of respiratory syncytial virus (RSV) lower respiratory tract infection has historically been one of the most frequent reasons for admission to Driscoll Children's Hospital. OBJECTIVE: The objective of this study was to examine the relationship of risk factors for a severe and complicated disease course to the treatment and hospital length of stay. METHODS: Subjects were identified through a retrospective review of the medical records of all patients discharged with a diagnosis of RSV lower respiratory tract infection during 9 of the 11 RSV seasons between July 1, 1991 and June 30, 2002. The RSV seasons from 1991-1992 to 1994-1995 were compared with the RSV seasons from 1995-1996 to 2001-2002 with regard to treatment and hospital course. RESULTS: There were a total of 3308 admissions. Compared with patients with no risk factors, higher percentages of patients with age <6 weeks, history of prematurity, congenital heart disease and neurologic disease were admitted to the pediatric intensive care unit (PICU) and required mechanical ventilation (P < 0.001). Also the hospital length of stay was longer for patients with each of these individual risk factors (P < 0.001). The hospital length of stay and the percentages of patients admitted to the PICU and requiring on mechanical ventilation increased as the number of risk factors increased from zero to 3 or more (P < 0.001). Of patients with 3 or more risk factors, the average hospital length of stay was 13.5 days; 67% were admitted to the PICU, and 47% required mechanical ventilation. Ribavirin use decreased in patients with each of the individual risk factors (P < 0.001) as well as in patients with one or more risk factors (P < 0.001). At the same time the PICU admission rate increased from 6.1% to 11.2% (P < 0.001). CONCLUSIONS: Patients with three or more risk factors were at very high risk for having a severe or complicated disease course associated with admission to the PICU, placement on mechanical ventilation and a longer hospital length of stay.     

Automated quantitation of peripheral blood neutrophil activation in patients with myocardial ischaemia

BACKGROUND: Coronary ischaemic syndromes are associated with neutrophil activation. The Bayer automated haematology analysers can detect increased light scatter of neutrophil populations, which correlates with neutrophil activation. We aimed to assess the role of an automated analyser in detecting systemic neutrophil activation in peripheral blood samples of patients with coronary ischaemia. METHODS: A prospective cross-sectional study was undertaken in 18 patients with chronic stable angina, 9 with unstable angina and 26 normal control subjects. Whole blood samples were taken to assess neutrophil count and light scatter, and serum samples were taken from some patients for assessment of Troponin T, C-reactive protein (CRP) and myeloperoxidase (MPO). In addition, whole blood was stimulated in vitro with interleukin (IL)-8 and N-formyl-methionyl-leucyl-phenylalanine (fMLP) to assess changes in neutrophil light scatter detected by the analyser. RESULTS: Neutrophil light scatter was increased in patients with chronic stable and unstable angina compared to normal control subjects (normal subjects 74.1 (73.3, 75.0) (mean arbitrary units (95% confidence intervals, (CI)) vs. 78.6 (76.9, 80.3) in the chronic stable angina group P<0.001 and 77.1 (75.3, 79.0) in the unstable angina group P<0.007). In vitro stimulation of whole blood produced comparable increases in neutrophil light scatter when morphological changes in neutrophils were demonstrable under electron microscopy. CONCLUSIONS: Automated measurement of neutrophil activation by light scatter is possible using the Advia 120 analyser and is superior to a neutrophil count in discriminating groups with angina. This technique may be useful in monitoring disease activity and progression in coronary artery disease and in guiding the use of anti-inflammatory therapies.     

California school board members' perceptions of factors influencing school nutrition policy

Enactment and enforcement of school nutrition policies represent key components in adolescent overweight and obesity prevention. This study determined: 1) California school board members' attitudes, perceptions, and motivations related to enactment of policies that support healthy eating in schools; and 2) barriers to adopting school policies that support healthy eating. To understand board members' decision-making process, key informant interviews were conducted and a survey was administered to 404 school board members. Though school board members care about the well-being of pupils, competing priorities limit the extent to which nutrition issues get addressed at board meetings. Members' decisions center primarily around academic achievement issues, yet they are interested in nutrition's overall impact on children's health and academic achievement.     

Vaccines and vaccine strategies against HIV

The HIV/AIDS pandemic is a global emergency and a preventive HIV vaccine is urgently needed. HIV has, however, proved a difficult pathogen to vaccinate against. This is largely because HIV has a very high mutation rate and can escape immune responses, it has a latent stage where it can rest silently integrated into host DNA, and neutralising antibodies that can neutralise diverse field strains have so far proved difficult to induce. There is however, considerable evidence now that HIV-specific CD4 and CD8 T cells can provide partial control of HIV replication and delay or prevent disease. Technologies to quantify and analyse HIV-specific T cells have advanced recently, and in particular ELISpot, intracellular cytokine staining and tetramer studies have provided clear analyses of the ability of HIV vaccines to induce T cell responses. The use of pools of overlapping HIV peptides as in vitro antigens has also provided a standardised reagent for accurate measurement of T cell responses. HIV protein vaccines have not induced broad neutralising antibodies or T cell responses and failed to protect humans in the only phase III efficacy trial yet completed. Viral vectors, such as canarypox, engineered to express HIV genes, have induced HIV-specific CD8 T cell responses in a minority of subjects in phase II trials and are proceeding to human efficacy trials. Currently, the most effective method of inducing CD8+ CTL immunity in non-human primates utilises priming with naked plasmid DNA and then boosting with recombinant viral vectors both encoding various parts of the HIV genome. Such vaccines have induced non-sterilising immunity to virulent Simian/Human immunodeficiency virus exposure in macaques and have entered phase I trials. Multiple other approaches are also being evaluated in what has become a global effort for a vaccine to prevent AIDS. Although an HIV vaccine is still a long way off, there is reason to be optimistic that a vaccine to prevent AIDS will eventually be developed.