SENTINEL1: Two-Season Study of Respiratory Syncytial Virus Hospitalizations among U.S. Infants Born at 29 to 35 Weeks' Gestational Age Not Receiving Immunoprophylaxis.

OBJECTIVE: The SENTINEL1 observational study characterized confirmed respiratory syncytial virus hospitalizations (RSVH) among U.S. preterm infants born at 29 to 35 weeks' gestational age (wGA) not receiving respiratory syncytial virus (RSV) immunoprophylaxis (IP) during the 2014 to 2015 and 2015 to 2016 RSV seasons. STUDY DESIGN: All laboratory-confirmed RSVH at participating sites during the 2014 to 2015 and 2015 to 2016 RSV seasons (October 1-April 30) lasting ≥24 hours among preterm infants 29 to 35 wGA and aged <12 months who did not receive RSV IP within 35 days before onset of symptoms were identified and characterized. RESULTS: Results were similar across the two seasons. Among infants with community-acquired RSVH (N = 1,378), 45% were admitted to the intensive care unit (ICU) and 19% required invasive mechanical ventilation (IMV). There were two deaths. Infants aged <6 months accounted for 78% of RSVH observed, 84% of ICU admissions, and 91% requiring IMV. Among infants who were discharged from their birth hospitalization during the RSV season, 82% of RSVH occurred within 60 days of birth hospitalization discharge. CONCLUSION: Among U.S. preterm infants 29 to 35 wGA not receiving RSV IP, RSVH are often severe with almost one-half requiring ICU admission and about one in five needing IMV.

Apnea induction for invasive lung function testing in infant olive baboons: Comparison of intravenous propofol versus hyperventilation.

BACKGROUND: In various types of pulmonary research, pulmonary function testing (PFT) is performed to quantify the severity of lung disease. Induction of apnea and positive pressure ventilation are required for accurate PFT measurements in non-cooperative subjects. We compared two methods of apnea induction in infant olive baboons (Papio anubis). METHODS: Pulmonary function testing results were compared during apnea induced by hyperventilation (CO2 washout) vs. intravenous propofol (1 dose 10 mg/kg). PFT was evaluated using a hot-wire pneumotachometer incorporated within an Avea ventilator in nine 1-month-old baboons. RESULTS: Propofol induced apnea faster and more reliably. In both groups, PFT values passed the statistical equivalence test and were not significantly different (Student's t-test). There was a trend toward less data variability after propofol administration. CONCLUSIONS: Intravenous propofol was non-inferior to CO2 washout for apnea induction in infant olive baboons. Propofol induced apnea faster and more reliably and yielded less variable PFT results.

Infant baboons infected with respiratory syncytial virus develop clinical and pathological changes that parallel those of human infants.

Respiratory syncytial virus (RSV) infection of the lower respiratory tract is the leading cause of respiratory failure among infants in the United States of America and annually results in >300,000 deaths worldwide. Despite the importance of RSV, there is no licensed vaccine, and no specific form of therapy. This is largely due to the absence of an appropriate animal model for the evaluation of vaccines and therapeutic agents. We inoculated anesthetized infant (4 wk) baboons (Papio anubis) with a human strain of RSV intranasally or intratracheally. Baboons were monitored daily for clinical changes. Anesthetized baboons were intubated at various intervals, and bronchoalveolar lavage (BAL) was performed for viral culture and determination of leukocyte counts. Sham-infected baboons served as controls. Necropsies were performed on infected baboons on days 1, 3, 5, 8, or 13 after inoculation, with pathological analysis and immunohistochemical staining of lung tissues to detect RSV antigen. Infected baboons developed tachypnea and reduced oxygenation peaking from 4 to 8 days after infection and persisting for ≥14 days. Virus was recoverable in BAL fluid up to 8 days following infection. Necropsy revealed intense interstitial pneumonia, sloughing of the bronchiolar epithelium, and obstruction of the bronchiolar lumen with inflammatory cells and sloughed epithelial cells. RSV antigen was identified in bronchiolar and alveolar epithelium. We conclude that RSV-infected infant baboons develop clinical and pathological changes that parallel those observed in human infants with RSV infection. The infant baboon represents a much-needed model for studying the pathogenesis of RSV infection and evaluating antivirals and vaccines.

Analysis of biennial outbreak pattern of respiratory syncytial virus according to subtype (A and B) in the Zagreb region.

BACKGROUND: The epidemic pattern of respiratory syncytial virus (RSV) in Croatia is biennial. In order to determine if the circulation of different RSV subtypes affects the outbreak cycle, the aim of the present study was to analyze the epidemic pattern of RSV in children in Croatia (Zagreb region) over a period of 3 consecutive years. METHODS: The study group consisted of 696 inpatients, aged 0-5 years, who were hospitalized with acute respiratory tract infections caused by RSV, in Zagreb, in the period 1 January 2006-31 December 2008. The virus was identified in nasopharyngeal secretions using direct immunofluorescence. The virus subtype was determined on real-time polymerase chain reaction. RESULTS: Of 696 RSV infections identified in children, subtype A virus caused 374 infections, and subtype B, 318. Four patients had a dual RSV infection (subtypes A and B). The period of study was characterized by four epidemic waves of RSV infections: the first, smaller, in the spring of 2006; the second, larger, in December 2006/January 2007; the third in spring 2008, followed by a fourth outbreak beginning in November of 2008. The biennial virus cycles were persistent although the predominant RSV subtype in the first two epidemic waves was subtype B, and in the second two it was subtype A. CONCLUSION: Over a 3 year period of observation, the biennial RSV cycle in Croatia cannot be explained by a difference in the predominant circulating subtype of RSV. Other unknown factors account for the biennial cycle of RSV epidemics in Croatia.

Mortality and morbidity among infants at high risk for severe respiratory syncytial virus infection receiving prophylaxis with palivizumab: a systematic literature review and meta-analysis.

OBJECTIVES: A systematic literature review and meta-analysis was performed to evaluate the impact of prophylaxis with palivizumab on mortality and morbidity associated with respiratory syncytial virus infection in infants at high risk (≤ 35 wks of gestational age, chronic lung disease, or congenital heart disease). DATA SOURCES: MEDLINE, EMBASE, and Current Contents were used. MEDLINE was searched from January 1, 1990 to May 16, 2007. The bibliographies of accepted studies and recent reviews and proceedings from the past 2 yrs were searched to identify additional relevant studies. STUDY SELECTION: Randomized controlled trials and prospective or retrospective cohort studies evaluating all-cause and respiratory syncytial virus-specific mortality, respiratory syncytial virus hospitalizations, and health care use in infants at high risk for respiratory syncytial virus infection receiving prophylaxis with palivizumab. DATA EXTRACTION: Data elements from each accepted study were extracted by one researcher and confirmed by a second researcher. Differences were resolved before data entry and analysis. DATA SYNTHESIS: A total of 2473 citations were screened and ten comparative studies of palivizumab prophylaxis evaluating >15,000 infants were included. Comparisons of mortality and hospitalization outcomes between infant groups using prophylaxis and not using prophylaxis were made using meta-analyses. CONCLUSIONS: Prophylaxis and nonprophylaxis infant groups appeared to be comparable at baseline. All-cause mortality during the respiratory syncytial virus season was 12 of 6380 (0.19%) for infants with prophylaxis vs. 33 of 8182 (0.53%) for infants without prophylaxis (Peto odds ratio, 0.30; 95% confidence interval, 0.17-0.55). Only five respiratory syncytial virus-specific deaths were reported, and the majority of the studies did not report respiratory syncytial virus-related deaths. The rate of respiratory syncytial virus hospitalization was significantly lower among preterm infants with prophylaxis compared with those without prophylaxis (4.1% vs. 10.4%; odds ratio, 0.35; 95% confidence interval, 0.25-0.47). Prophylaxis with palivizumab was associated with a reduction in all-cause mortality and respiratory syncytial virus hospitalization among preterm infants at high risk. Additional research on cause of death among infants at high risk is needed.

Comparison of Amikacin Pharmacokinetics in Neonates With and Without Congenital Heart Disease.

OBJECTIVES: The primary objective was to compare the volume of distribution (Vd), clearance (CL), elimination rate (Ke), and half-life (t½) of amikacin in neonates with cyanotic defects, acyanotic defects, and controls, adjusted for gestational and postnatal age. Secondary objectives were to compare the incidence of acute kidney injury (AKI) between controls and the congenital heart disease (CHD) group and to identify potential risk factors. METHODS: This retrospective cohort study included neonates receiving amikacin from January 1, 2013 to August 31, 2016. Patients were excluded if concentrations were not appropriately obtained or if AKI or renal anomalies were identified prior to amikacin initiation. Congenital heart disease was classified as acyanotic or cyanotic. Patients with CHD were matched 1:1 with non-CHD controls according to postmenstrual age. Bivariate analyses were performed using Wilcoxon-Mann-Whitney test, Pearson χ2 tests, or Fisher exact as appropriate with a p value <0.05. Regression analyses included logistic and analysis of covariance. RESULTS: Fifty-four patients with CHD were matched with 54 controls. Median (IQR) postnatal age (days) at amikacin initiation significantly differed between CHD and controls, 3.0 (1.0-16.0) versus 1.0 (1.0-3.0), p = 0.016. After adjusting for gestational and postnatal age, there was no difference in the mean (95% CI) Vd (L/kg) and CL (L/kg/hr) between CHD and controls, 0.47 (0.44-0.50) versus 0.46 (0.43-0.49), p = 0.548 and 0.05 (0.05-0.05) versus 0.05 (0.05-0.05), p = 0.481, respectively. There was no difference in Ke or t½ between groups. There was no difference in AKI between the CHD and controls, 18.5% versus 9.3%, p = 0.16. CONCLUSIONS: Clinicians should consider using standard amikacin dosing for neonates with CHD and monitor renal function, since they may have greater AKI risk factors.

Maternal immunization with RSV fusion glycoprotein vaccine and substantial protection of neonatal baboons against respiratory syncytial virus pulmonary challenge.

Globally, human respiratory syncytial virus (RSV) is a major cause of severe lower respiratory infection in infants and young children. There are no licensed vaccines despite the high worldwide disease burden. RSV fusion (F) glycoprotein vaccine is the most advanced candidate for maternal immunization. In this report, a baboon maternal immunization model was used to assess the immunogenicity and protection of infants against pulmonary challenge with human RSV/A. Vaccination in the third trimester produced high anti-RSV F IgG titers and virus-neutralizing antibodies. Infants born to immunized females had high levels of serum RSV antibodies that were comparable to maternal levels at birth and persisted for over 50 days with a half-life of 14-24 days. Furthermore, infants from immunized females and challenged with RSV/A were healthy, developed less severe disease, and had only mild pulmonary inflammatory changes whereas infants born to non-vaccinated females developed more severe disease with marked to moderate interstitial pneumonia, pulmonary edema, and bronchiolar obstruction. These results support the further development of the RSV F vaccine for maternal immunization.

Does the viral subtype influence the biennial cycle of respiratory syncytial virus?

BACKGROUND: The epidemic pattern of respiratory syncytial virus (RSV) is quite different in regions of Europe (biennial epidemics in alternating cycles of approximately 9 and 15 months) than in the Western Hemisphere (annual epidemics). In order to determine if these differences are accounted for by the circulation of different RSV subtypes, we studied the prevalence of RSV subtype A and B strains in Zagreb County from 1 January 2006 to 31 December 2007. RESULTS: RSV was identified in the nasopharyngeal secretions of 368 inpatients using direct fluorescence assays and/or by virus isolation in cell culture. The subtype of recovered strains was determined by real-time PCR. Of 368 RSV infections identified in children during this interval, subtype A virus caused 94 infections, and subtype B 270. Four patients had a dual RSV infection (subtypes A and B). The period of study was characterized by two epidemic waves of RSV infections-one, smaller, in the spring of 2006 (peaking in March), the second, larger, in December 2006/January 2007 (peaking in January). The predominant subtype in both outbreaks was RSV subtype B. Not until November 2007 did RSV subtype A predominate, while initiating a new outbreak continuing into the following calendar year. CONCLUSION: Though only two calendar years were monitored, we believe that the biennial RSV cycle in Croatia occurs independently of the dominant viral subtype.

Eleven consecutive years of respiratory syncytial virus outbreaks in Croatia.

BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of severe lower respiratory tract infections (LRTI) in infants. The aim of the present study was to analyze the epidemiologic characteristics of RSV outbreaks in Croatian children. METHODS: Over a period of 11 consecutive years (1994-2005), 3435 inpatients with acute respiratory infections (ARI) aged from birth to 10 years and were residing in Zagreb County were tested for infection with RSV and other respiratory viruses at the Virology Department, Croatian National Institute of Public Health. RSV was identified in nasopharyngeal secretions by isolation on cell culture and/or detection with monoclonal antibodies using a direct fluorescence assay. RESULTS: RSV was the most common causative agent of ARI (42.2%; 658/1559) for the infants 0-6 months of age. It was also the etiologic agent of LRTI in 49% (495/1010) of infants of similar age. RSV was demonstrated in 56.5% (382/676) of infants with bronchiolitis, and in 36.5% (49/134) of those with pneumonia in this age group. CONCLUSION: The overall prevalence of RSV infection in Croatian children with acute respiratory illness, and its occurrence in various age groups, has remained stable over the past decade. RSV was found to be the most common cause of bronchiolitis occurring throughout childhood (52.7%; 482/913).

Impact of Ceftazidime Use on Susceptibility Patterns in the Neonatal Intensive Care Unit.

BACKGROUND: Ceftazidime use in the neonatal intensive care unit (NICU) has increased after a cefotaxime shortage. The impact of this change is unknown. The purpose was to assess the effect of increased ceftazidime use on susceptibilities of Gram-negative organisms in the NICU. METHODS: Retrospective study of Gram-negative isolates identified in blood, urine, cerebrospinal fluid, tracheostomy, abdominal fluid and pleural fluid cultures from a single-center NICU over a 5-year period. Duplicate cultures that occurred within 90 days were noted. Pre- and postshortage periods were defined based on cessation of cefotaxime. Third- and fourth-generation cephalosporin susceptibility rates were compared between periods, as well as rates of extended-spectrum beta-lactamase (ESBL) Escherichia coli and Klebsiella species. RESULTS: Analysis included 666 isolates. Twelve (1.8%) were duplicate isolates that occurred after a 90-day period. The preshortage period included 464 (69.7%) isolates, and the postshortage included 202 (30.3%). No significant differences in susceptibility rates were noted when excluding duplicates. No difference in ESBL rates for E. coli were noted between periods (3.8% vs. 4.9%, P =1.000). No ESBL-positive Klebsiella species were identified. A post-hoc analysis of duplicate isolates demonstrated significant lower susceptibility rates for Pseudomonas aeruginosa to ceftazidime (risk ratio 0.58; 95% CI: 0.43-0.79) and cefepime (risk ratio 0.66; 95% CI: 0.51-0.86). CONCLUSIONS: Ceftazidime use did not appear to affect susceptibility rates for third- and fourth-generation cephalosporins for most Gram-negative organisms in the short-term of 1.5 years. However, susceptibility rates for P. aeruginosa decreased when evaluating duplicate isolates. Long-term monitoring is needed to assess the true impact.

Deficits in urological knowledge among medical students and primary care providers: potential for impact on urological care.

PURPOSE: Recent data indicate a decline in the urological education of third and fourth year medical students. To determine if this decline has an impact on the treatment of patients we performed a survey to evaluate the general level of knowledge, attitudes and practices with regard to common urological issues seen in a general medical practice among medical students and faculty involved in primary care at an academic institution. MATERIALS AND METHODS: A confidential questionnaire was distributed to attendings, residents and fellows, and the clinical medical students at our academic institution to ascertain how they evaluate and treat patients with common urological complaints. All responses were entered into SPSS statistical software. RESULTS: A total of 300 surveys were distributed, 150 of which were returned with complete information for data analysis. Knowledge with regard to various conditions including hematuria, recognition of an age specific abnormality in serum prostate specific antigen and overactive bladder was low for all groups. Furthermore, respondents demonstrated a low likelihood of requesting formal urological evaluation for these conditions. Exposure to a urology elective in medical school had a positive impact on some areas of urological evaluation. CONCLUSIONS: General urological knowledge with regard to the primary care setting is insufficient. The potential for impact on patient care is enormous. These data highlight the need for a definitive urological curriculum in medical school as well as continued education at the resident and faculty level with regard to evaluation, management and recognition of when to request formal urological evaluation in the primary care setting.

Respiratory syncytial virus and influenza virus infections: observations from tissues of fatal infant cases.

Respiratory syncytial virus (RSV) and influenza virus are common causes of infantile lower respiratory tract infection (LRTI). It is widely believed that both viral replication and inappropriately enhanced immune responses contribute to disease severity. In infants, RSV LRTI is known to be more severe than influenza virus LRTI. We compared cytokines and chemokines in secretions of infants surviving various forms of respiratory illness caused by RSV or influenza viruses, to determine which mediators were associated with more severe illness. We analyzed lung tissue from fatal cases of RSV and influenza LRTI to determine the types of inflammatory cells present. Quantities of lymphocyte-derived cytokines were minimal in secretions from infants with RSV infection. Concentrations of most cytokines were greater in influenza, rather than RSV, infection. Lung tissues from fatal RSV and influenza LRTI cases demonstrated extensive presence of viral antigen and a near absence of CD8-positive lymphocytes and natural killer cells, with marked expression of markers of apoptosis. Severe infantile RSV and influenza virus LRTI is characterized by inadequate (rather than excessive) adaptive immune responses, robust viral replication and apoptotic crisis.

The biennial cycle of respiratory syncytial virus outbreaks in Croatia.

The paper analyses the epidemic pattern of respiratory syncytial virus (RSV) outbreaks in children in Croatia. Over a period of 11 consecutive winter seasons (1994-2005) 3,435 inpatients from Zagreb County aged from infancy to 10 years who were hospitalised with acute respiratory tract infections were tested for RSV-infection. RSV was identified in nasopharyngeal secretions of patients by virus isolation in cell culture and by detection of viral antigen with monoclonal antibodies. In the Zagreb area, RSV outbreaks were proven to vary in a two-year cycle, which was repeated every 23-25 months. This biennial cycle comprised one larger and one smaller season. Climate factors correlated significantly with the number of RSV cases identified only in the large seasons, which suggests that the biennial cycle is likely to continue regardless of meteorological conditions. Knowledge of this biennial pattern should be useful in predicting the onset of RSV outbreaks in Croatia, and would facilitate planning for the prevention and control of RSV infections in the region.

The immune response to respiratory syncytial virus infection: friend or foe?

The immune response to respiratory syncytial virus (RSV) infection has fascinated and frustrated investigators for decades. After adverse responses to early attempts at vaccination, it became popularly held that disease following infection was related to overly aggressive immune responses. However, recent data illustrate that severe forms of disease are related to inadequate, rather than hyperresponsive, adaptive immune reactions. Thus, recovery from primary (and perhaps later) RSV infection is dependent on the quality of innate immune responses. These findings should have enormous significance to the development of vaccines and antiviral compounds.

Temperature, humidity, and ultraviolet B radiation predict community respiratory syncytial virus activity.

To obtain knowledge of how meteorological conditions affect community epidemics of respiratory syncytial virus (RSV) infection, RSV activity was recorded year-round in 9 cities that differ markedly in geographic location and climate. Local weather conditions were correlated with weekly or monthly RSV cases. Similar reports from other areas varying in climate were also reviewed. Results demonstrated that for all sites combined, weekly RSV activity was related to temperature in a bimodal fashion, with peaks of activity at temperatures more than 24-30 degrees C and at 2-6 degrees C. RSV activity also was greatest at 45-65% relative humidity. RSV activity was inversely related to ultraviolet B (UVB) radiance at 3 sites where this could be analyzed; the fourth site had minimal amounts of annual UVB radiance. At sites with persistently warm temperatures and high humidity, RSV activity was continuous throughout the year, peaking in summer and early autumn. In temperate climates, RSV activity was maximal during winter, correlating with lower temperatures. In areas where temperatures remained cold throughout the year, RSV activity again became nearly continuous. These data led us to conclude that community activity of RSV is substantial when both ambient temperatures and absolute humidity are very high, perhaps reflecting greater stability of RSV in aerosols; transmission of RSV in cooler climates is inversely related to temperature, possibly as a result of increased stability of the virus in secretions in the colder environment; and UVB radiation may inactivate the virus in the environment or influence susceptibility to RSV by altering host resistance.

Intravenous Immunoglobulin Therapy for Cerebral Vasculitis Associated with Rocky Mountain Spotted Fever.

Rocky Mountain spotted fever is a tick-borne illness that is prevalent in the south and the central United States, primarily during the summer months. Patients with delayed diagnosis can experience increased mortality and morbidity, particularly poor neurological outcome. We present a case of a 7-year-old girl with Rocky Mountain spotted fever who was admitted with severe neurological changes and septic shock on day 8 of illness. She was initially diagnosed with Kawasaki disease and treated with intravenous immunoglobulin. Her treatment also included doxycycline, vancomycin, and ceftriaxone due to concerns regarding Rocky Mountain spotted fever and bacterial sepsis. During hospitalization, the patient required mechanical ventilation for respiratory distress, inotropic support, and fluid resuscitation for hypotension. Titers for Rocky Mountain spotted fever were ultimately positive, with magnetic resonance imaging of the brain demonstrating numerous punctate foci of restricted diffusion within the supratentorium, including the corpus callosum and basal ganglia. Although the patient presented late in the disease course, she ultimately had a good neurological outcome. We theorized that administration of intravenous immunoglobulin prevented ongoing neurological injuries from the cerebral vasculitis, which are associated with Rocky Mountain spotted fever.

Comparison of Amikacin Pharmacokinetics in Neonates Following Implementation of a New Dosage Protocol.

OBJECTIVES: The primary aim was to compare attainment of goal serum amikacin concentrations using two dosage regimens in patients admitted to a neonatal intensive care unit. Secondary objectives included comparison of percentages of supratherapeutic trough concentrations, and subtherapeutic and supratherapeutic peak concentrations. METHODS: This was an Institutional Review Board-approved, retrospective study of neonates receiving amikacin during January-December 2013 (group 1) and January-December 2014 (group 2). Group 1 received amikacin dosage consistent with published recommendations, whereas group 2 was dosed using a modified protocol that was based on postmenstrual and postnatal age. Goal serum amikacin peak concentration was defined as 20 to 35 mg/L; hence, subtherapeutic and supratherapeutic peak concentrations were defined as <20 mg/L and >35 mg/L, respectively. Supratherapeutic trough concentrations were >8 mg/L. Between-group analysis was performed using Wilcoxon-Mann-Whitney test, Student t-test or χ2, or Fisher exact analysis as appropriate with a p value <0.05. RESULTS: A total of 278 neonates were included (group 1: n = 144; group 2: n = 134). Most patients were male (60%) and were admitted for prematurity or respiratory distress (77%). The median gestational age in group 1 was 34.4 weeks (range, 30.0-37.9 weeks) versus group 2 at 36.9 weeks (range, 31.4-38.9 weeks), whereas the postnatal age was similar between both groups at 4 days. There was a significant increase in attaining goal peak amikacin concentrations between groups 1 and 2, 34% versus 84%, p < 0.001, and decrease in supratherapeutic peak concentrations, 65% versus 12%, p < 0.001. There was no significant difference in subtherapeutic peak or supratherapeutic trough concentrations. CONCLUSIONS: A modified neonatal amikacin dosage protocol resulted in increased peak amikacin serum concentration compared with published dosage recommendations. Future research should focus on determination of the optimal dosage regimen in neonates.

Respiratory syncytial virus bronchiolitis : current and future strategies for treatment and prophylaxis.

Respiratory syncytial virus (RSV) is the most important cause of viral lower respiratory tract illness in infants and children worldwide and is responsible for over 120 000 annual hospitalizations in infants in the US alone. RSV is also recognized as a major respiratory viral pathogen in the elderly and other high-risk populations. Bronchiolitis, pneumonia, apnea, respiratory failure, and death are well known manifestations of severe acute RSV disease. RSV infection has also been associated with recurrent wheezing in children, but the mechanisms involved in this association are not completely understood. The host immune response plays a significant role in controlling the infection but is likely also involved in augmenting the disease through pathways that have not been completely identified. The treatment options for RSV infection are very limited. Ribavirin, corticosteroids, and bronchodilators are not used routinely because they have not proven to be sufficiently effective. Education of caregivers, strict handwashing, and avoidance of exposure to environmental factors associated with severe forms of RSV infection are among the most effective preventive means. Passive immunization with monoclonal antibodies provides protection against severe RSV disease in high-risk children. Clinical trials to evaluate the safety and efficacy of a second-generation monoclonal antibody are underway. Efforts to develop a safe and effective RSV vaccine have continued despite the poor outcomes observed following the administration of formalin-inactivated formulations in the 1960s. In the last decade, live attenuated vaccines (including those developed by recombinant techniques) and purified subunit vaccines have all been evaluated in humans. Results of clinical trials have been encouraging, but the availability of a safe and effective RSV vaccine is not a reality yet. Better prevention strategies will have an impact, not only on acute morbidity caused by RSV, but will also likely have an effect on ameliorating the chronic consequences of this disease.

Fusarium Osteomyelitis in a Patient With Pearson Syndrome: Case Report and Review of the Literature.

Fusarium species are ubiquitous fungi causing a wide array of infections, including invasive disease in the immunosuppressed. We present a fusarium bone infection in a child with Pearson syndrome and review the literature. Ten cases of fusarium osteomyelitis were reported in the past 40 years, and we review the treatments.

Innate immune responses in respiratory syncytial virus infections.

Respiratory syncytial virus (RSV) is the most important viral respiratory pathogen of early life. Studies of the immune response in general (and the innate response in particular) to this agent are of interest for a number of reasons. First, severe forms of illness may be a result of enhanced immunologic responsiveness to viral constituents at the time of infection. Secondly, the immune response to RSV may consist principally of innate immune responses at the time of maximum severity of illness. Third, RSV infection in infancy may be linked via immune mechanisms to the development of childhood wheezing. Finally there are no meaningfully effective forms of therapy for RSV infection, and elucidation of the immune response may suggest new therapeutic approaches. This review will summarize our current knowledge of innate immune responses to RSV infection. Specifically we will review early interactions of the virus with surfactant proteins and Toll-like receptors, chemokine release from infected cells, cytokine release from activated inflammatory cells, activation of neuroimmune pathways, generation of dendritic cells, the release of soluble mediators of airway obstruction, and genetic polymorphisms associated with RSV-related illness.