Stanley G. Cron

Correlates of immunity to respiratory syncytial virus (RSV) associated-hospitalization: establishment of minimum protective threshold levels of serum neutralizing antibodies

OBJECTIVE To determine if respiratory syncytial virus (RSV) specific, serum antibody titers correlate with protection against RSV associated-hospitalization at all ages. DESIGN Participants who were enrolled in a trial to determine the frequency of specific virus infections associated with hospitalization [J. Am. Med. Assoc. 283 (2000) 499] were included in our analysis if they were enrolled from July 1991 to June 1993, had a culture for virus isolation, and provided blood samples at hospitalization and 14-60 days later. RSV infection was defined by a positive culture and/or serology. Microneutralization, ELISA to the fusion (F) protein and Western blot were the serological assays that were used to determine correlates of immunity. RESULTS One hundred and seventy-five individuals, 1 month to 89 years old, out of 538 patients hospitalized with an acute respiratory infection met the criteria for analysis. RSV associated-hospitalization occurred in 11 (40.7%) of 27 infants (<1 year), 8 (38.1%) of 21 young children (1 to <5 years), and 15 (11.8%) of 127 children and adults (> or =5 years). At the time of hospitalization, geometric mean neutralizing antibody titers (log(2)) to RSV/A and RSV/B, and geometric mean binding antibody titer (log(2)) to F protein were significantly higher in patients with non-RSV associated-hospitalization compared to those with RSV associated-hospitalization (RSV/A: 7.9 versus 6.1, P<0.001; RSV/B: 9.4 versus 7.3, P<0.001; ELISA-F, 13.9 versus 12.6, P=0.01). For every 1 log(2) increase in titer of neutralizing antibodies to RSV/A and RSV/B, and binding antibody to F protein there was a significant increase in the likelihood of not having an RSV associated-hospitalization by 22.3, 25, and 24.4% respectively. A minimal protective threshold titer of > or =6.0 (odds ratio 3.5; 95% CI 1.4-9.1) and > or =8.0 log(2) (odds ratio 2.9; 95% CI 1.1-7.7) against RSV associated-hospitalization was established for neutralizing antibodies to RSV/A and RSV/B; a threshold titer could not be established for binding antibody to F protein. CONCLUSION Participants with naturally acquired serum neutralizing antibody levels at least equal to the minimal protective threshold titer were approximately three times more likely not to have an RSV associated-hospitalization. We speculate that achieving a minimal protective threshold antibody titer through active immunization will significantly reduce RSV associated-hospitalization among all ages.

Combination Drug Therapy for Cryptosporidiosis in AIDS

Aside from effective antiretroviral therapy, there is no consistently effective antiparasitic therapy for cryptosporidiosis in AIDS. The purpose of this study was to assess safety, efficacy, and durability of combination therapy with paromomycin and azithromycin for chronic cryptosporidiosis. Patients with AIDS, chronic cryptosporidiosis, and < 100 CD4 cells/microL were treated with open-label paromomycin (1.0 g twice a day) plus azithromycin (600 mg once a day) for 4 weeks, followed by paromomycin alone for 8 weeks. In 11 patients, median stool frequency decreased from 6.5/day (baseline) to 4.9/day (week 4) and 3.0/day (week 12). Median reductions in 24-h oocyst excretion were 84%, 95%, and >99% at 2, 4, and 12 weeks, respectively. None of the responses were attributable to antiretrovirals. Of 5 survivors at 12-30 months of follow-up, 3 remain asymptomatic off medications, and 2 have chronic, mild diarrhea. Treatment of cryptosporidiosis with azithromycin and paromomycin was associated with significant reduction in oocyst excretion and some clinical improvement.

Immunopathogenesis of Respiratory Syncytial Virus Bronchiolitis

BACKGROUND The objective of this study was to elucidate the relation between respiratory syncytial virus (RSV) infection and cytokine/chemokine concentrations, as well as the impact that these factors have on the severity of bronchiolitis. METHODS Children <24 months old who presented to the emergency department with clinical symptoms of bronchiolitis were prospectively enrolled in the study. Nasal-wash samples were analyzed to identify viral pathogens and to quantify RSV and cytokine/chemokine concentrations. Severe cases of disease were defined as those requiring hospitalization, and severity was further determined on the basis of the duration of supplemental-oxygen and/or intravenous-fluid therapy. RESULTS A total of 101 children were enrolled, 63 of whom were infected with RSV and 13 of whom were infected with other respiratory viruses; in 22 children, no virus was detected. RSV bronchiolitis was associated with a greater inflammatory response than was non-RSV bronchiolitis, although RSV infection was not associated with more-severe disease. Levels of interleukin (IL)-6, IL-8, IL-10, interferon (IFN)-gamma, and macrophage inflammatory protein (MIP)-1beta were significantly inversely correlated with the duration of supplemental-oxygen therapy. CONCLUSION The robust inflammatory response associated with RSV infection does not contribute to the severity of RSV bronchiolitis any more than it contributes to the severity of non-RSV bronchiolitis. Elevated levels of proinflammatory mediators IL-6, IL-8, IFN-gamma, and MIP-1beta, as well as of the regulatory cytokine IL-10, may be protective against hypoxia in bronchiolitis.

Immunogenicity of a new purified fusion protein vaccine to respiratory syncytial virus: A multi-center trial in children with cystic fibrosis

A third generation, purified fusion protein (PFP-3) vaccine was developed to prevent severe respiratory syncytial virus (RSV) disease in high-risk groups. A phase II, multi-center, adjuvant-controlled trial was performed in RSV seropositive children with cystic fibrosis (CF); 151 received the adjuvant-control and 143 received the vaccine. Details of the vaccine-induced immune response are presented. At enrollment, RSV-specific, serum antibodies were comparable between both groups. A highly sensitive and specific serum antibody vaccine profile was established for the PFP-3 vaccine. At post-vaccination and end-of-study, RSV-specific, neutralizing antibody (Nt Ab) and binding antibody (Bd Ab) to the fusion (F) protein were significantly higher in PFP-3 vaccinees. After 28 days post-vaccination, Nt Ab and Bd Ab to F protein titers declined slowly at rates of 0.23 and 0.37 log2 per month, respectively. The PFP-3 vaccine-induced a robust immune response that lasted throughout the RSV season.

Stress Experienced by Stroke Survivors and Spousal Caregivers During the First Year After Discharge from Inpatient Rehabilitation

Abstract Purpose: This study describes levels of stress in stroke survivors and spousal caregivers and identifies predictors of stress in couples during their first year at home. Method: The Perceived Stress Scale (PSS) was administered to 159 stroke survivors and caregivers at discharge and at 3, 6, 9, and 12 months. Other variables tested included stroke survivor function (FIM™), health status, mutuality, stroke impact (SIS), caregiver coping (F-COPES), support (MOS Social Support Survey), and preparedness. Repeated measures analyses of PSS scores were conducted with linear mixed models for stroke survivors and caregivers. Results: PSS scores for stroke survivors and caregivers were positively correlated (p < .01). Scores decreased significantly over the year, but caregivers had higher scores initially and decreased less. Stroke survivor function was a significant predictor of stress for both survivors and caregivers. Preparation was the most powerful predictor of stress in caregivers, whereas mutuality was the strongest predictor for stroke survivors. Good health, social support, and coping were associated with less stress. Conclusions: Stress is increased by poor function and mediated by internal and external buffers including health, the dyadic relationship, coping ability, and social support. More research using a dyadic research approach is needed to better understand stress within couples.

HLA-Restricted CD8+ Cytotoxic T Lymphocyte, Interferon-γ, and Interleukin-4 Responses to Respiratory Syncytial Virus Infection in Infants and Children

CD8+ cytotoxic T lymphocyte (CTL) activity, interferon (IFN)-gamma, and interleukin (IL)-4 production were evaluated in a blinded manner among respiratory syncytial virus (RSV)-infected newborns and their mothers for 3 epidemic seasons. Most mothers (80%) exhibited RSV-specific CD8+ CTL activity. Twenty (80%) of the 26 infants exhibited significant RSV-specific CTL activity during or after their first RSV season. CTL frequency increased with RSV infection rate, reaching 75% by the end of the third season. Most infants who shed virus (75%) had a medically attended lower respiratory tract disease (LRD). In the first year, RSV-infected infants (virus culture and antibody increase) were more likely to develop CTL activity (10 of 13) than were uninfected infants (1 of 5; P=.02). Infants with CTL activity in the first year were less likely to have an LRD in the second year. CD8+ CTL levels correlated positively with IFN-gamma (P<.001) and inversely with IL-4 (P=.03). Contribution of CD8+ CTL and IFN-gamma in the control of RSV disease in infants and children is implicated.

Predictors of Life Satisfaction in Stroke Survivors and Spousal Caregivers After Inpatient Rehabilitation

&NA; A global measure of life satisfaction has become increasingly important as an adjunctive outcome of healthcare interventions for people with disabilities, including those caused by stroke. Life satisfaction of stroke survivors may affect caregiving spouses, as well. The purpose of this study was to identify, among many physical and psychosocial variables, specific variables that were associated with life satisfaction at 12 months after discharge from inpatient rehabilitation, and variables that were predictive of life satisfaction 1 year later (at 24 months). Between 12 and 24 months, life satisfaction decreased for stroke survivors, while it increased for caregiving spouses. The relationship between the couple (mutuality) was the only variable that was a significant predictor of life satisfaction for both stroke survivors and their spouses.

Long-term health-related quality of life of stroke survivors and their spousal caregivers.

ABSTRACTBecause treatment for stroke has improved, individuals are living longer with the effects of a stroke. The resulting long-term impairment can affect both stroke survivors’ and their caregivers’ health-related quality of life (HRQOL). Few studies have examined the HRQOL of stroke survivors and their caregivers greater than 2 years poststroke. The stroke survivors and their spousal caregivers (n = 30 dyads) who had previously completed a 12-month study after discharge from inpatient rehabilitation were assessed at 3–5 years poststroke. The HRQOL and related outcomes were measured for stroke survivors and caregivers. Data from baseline to 12 months were used in conjunction with data from this study. Linear mixed models were used to analyze the change in repeated measures over time. Multiple linear regression was used to analyze the relationship of generic HRQOL to related psychosocial outcomes. The stroke survivors were an average of 4.68 years poststroke. The mean age for stroke survivors and caregivers was 70.8 and 64.9 years, respectively. Most stroke survivors were men (80%) and non-Hispanic White (70%). Among stroke survivors, depression decreased from baseline to 12 months (p = .04) but increased from 12 months to the end of follow-up (p = .003). The caregivers’ depression decreased from baseline to all time points (p = .015). Stroke-specific HRQOL showed statistically significant (p < .03) decreases between 12 months and end of follow-up. Increased number of illnesses and older age were associated with caregivers’ lower physical HRQOL score (p = .004). Higher depression was associated with lower mental HRQOL score for both caregivers and stroke survivors (p = .003 and p = .011, respectively). Both stroke survivors and caregivers continue to experience negative stroke-related health outcomes for many years after the initial stroke; some of these outcomes even worsen over time. These findings illustrate the need for ongoing psychological and medical evaluation for both long-term stroke survivors and caregivers. Development and testing of targeted behavioral interventions are also warranted.

CRYPTOSPORIDIOSIS IN HOUSTON, TEXAS : A REPORT OF 95 CASES

&NA; Abbreviations used in this article: AIDS, acquired immunodeficiency syndrome; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CMV, cytomegalovirus; C. parvum, Cryptosporidium parvum; ELISA, enzyme‐linked immunoadsorbent assay; HCHD, Harris County Hospital District; HIV, human immunodeficiency virus; IFN, interferon; IL, interleukin; LDH, lactate dehydrogenase; TNF, tumor necrosis factor.

Risk factors for fatigue severity in primary brain tumor patients

In addition to neurologic symptoms, fatigue is commonly reported in patients with primary brain tumors during radiation therapy and in long–term survivors of low–grade brain tumors. Other factors have not been explored. The aim of this study was to identify demographic and clinical factors that predict fatigue severity and to evaluate the association of fatigue with other symptoms throughout the disease trajectory.