Administration of the first dose of palivizumab immunoprophylaxis against respiratory syncytial virus in infants before hospital discharge: what is the evidence for its benefit?

BACKGROUND: Palivizumab is 1 of 2 agents used to prevent severe lower respiratory tract disease due to respiratory syncytial virus (RSV) infection. The American Academy of Pediatrics and the American College of Obstetricians and Gynecologists recommend administering the first dose of RSV immunoprophylaxis to eligible infants before hospital discharge. Unfortunately, third-party payers frequently do not separately reimburse administration of this therapy to hospitalized infants. OBJECTIVE: Because palivizumab is commonly used to provide RSV immunoprophylaxis, we systematically reviewed all published data on this drug to determine whether the evidence supports the recommendation of administering the first dose before hospital discharge. METHODS: MEDLINE was searched for all articles published in English from January 1, 1996, to October 31, 2003, using the search terms palivizumab and Synagis, and the following data were extracted onto a standardized form: author(s), year of publication, study design, patient population, sample size, criteria used for administration of RSV prophylaxis, location of palivizumab prophylaxis (inpatient or outpatient), parental satisfaction with administration of prophylaxis, incidence of RSV infection, and hospitalization rates for RSV. All selected publications were reviewed to determine whether they reported differences in the incidence of RSV infection or hospitalization in patients who received palivizumab before discharge compared with those who received it after discharge. Only those publications that specifically documented administration of the first dose of palivizumab before hospital discharge were included in the final analysis. RESULTS: Six of the 166 studies reviewed met the selection criteria. Although all 6 studies reported reduced RSV hospitalization rates with palivizumab prophylaxis, no study directly compared inpatient and outpatient administration with regard to parental satisfaction or rates of RSV infection or hospitalization. Furthermore, based on the data in these studies, it was not possible to detect any differences in parental satisfaction or rates of RSV infection or hospitalization between the 2 locations of administration. CONCLUSIONS: Based on our literature review, there is no evidence to support the recommendation that palivizumab be administered before hospital discharge in every infant who meets the criteria for RSV immunoprophylaxis. Eligible infants may be given the initial dose of RSV prophylaxis as outpatients, reducing the cost to institutions that currently provide palivizumab before hospital discharge.     

Potential of KM+ lectin in immunization against Leishmania amazonensis infection

In the present study we evaluated Canavalia brasiliensis (ConBr), Pisum arvense (PAA) and Artocarpus integrifolia (KM+) lectins as immunostimulatory molecules in vaccination against Leishmania amazonensis infection. Although they induced IFN-gamma production, the combination of the lectins with SLA antigen did not lead to lesion reduction. However, parasite load was largely reduced in mice immunized with KM+ lectin and SLA. KM+ induced a smaller inflammatory reaction in the air pouch model and was able to inhibit differentiation of dendritic cells (BMDC), but to induce maturation by enhancing the expression of MHC II, CD80 and CD86. These observations indicate the modulatory role of plant lectins in leishmaniasis vaccination may be related to their action on the initial innate response.     

Critical Requirement for Graft Passenger Leukocytes in Allograft Tolerance Induced by Donor Blood Transfusion

Tolerance to a vascularized allograft can be induced in adultanimals by pregraft donor-specific blood transfusion (DST). Mechanismsunderlying this effect appear to depend on unresponsiveness ofalloreactive T-helper cells. In this study, we examined the roles ofDST and cellular components of the allograft that are important ininducing T-cell unresponsiveness in a rat model. DST alone did nottolerize alloreactive recipient T-helper cells, but the combination ofDST and heart allograft induced profound inhibition of the antidonorproliferative response in spleen but not in lymph node cells. Whenheart allografts were depleted of passenger leukocytes by pretreatingthe donor with cyclophosphamide or by parking the graft for 2 months ina tolerant recipient, tolerance induction in DST-treated recipients wasabrogated. Tolerance could then be restored in a majority ofDST-treated recipients of passenger leukocytes depleted grafts byinjecting them at the time of grafting with donor, but not third-party,dendritic cells. This indicates that graft passenger leukocytes, mostlikely dendritic cells, are required for DST-induced allografttolerance.     

A protein free diet uncovers the potential age-difference in the hepatic detoxifying system,glutathione S-transferase,in female mice

Female C57BL mice of six different ages (from 6 to 26 months) were given a protein free-diet (PFD) for 1 week and then given a normal diet (ND). Mice were examined for enzyme activities of glutathione S-transferase (GST) in the hepatic cytosol fraction using l-chloro-2, 4-dinitrobenzene (CDNB) as substrate. Enzyme activities were very close among the six different age groups when examined for basal levels as well as after 1 week of PFD. However, a remarkable age difference became manifest when animals were examined 2 days after the start of ND refeeding following 1 week of PFD. In young animals (6, 8 months), activities became much higher than their respective basal levels while in old animals (24, 26 months) enzyme levels remained significantly lower than their basal levels on day 2 of ND refeeding. A significant negative linear correlation between enzyme activities (Y axis) and animal age (X axis) was demonstrated only on day 2 or 3 of ND refeeding, while in control animals or animals given 1 week of PFD diet, no significant correlation could be found between enzyme activities and animal age. We conclude that liver cytosolic GST activity is a function of animal age only after a dietary manipulation such as a PFD and ND refeeding, while basal GST activities remain stable throughout the observation period of animal age.     

Increased cardiac sympathetic drive and reduced vagal modulation following endothelin receptor antagonism in healthy conscious rats

1. The present study evaluated changes in autonomic control of the cardiovascular system in conscious rats following blockade of endothelin (ET) receptors with bosentan. 2. Rats were treated with bosentan or vehicle (5% gum arabic) for 7 days by gavage. 3. Baseline heart rate (HR) was higher in the bosentan-treated group compared with the control group (418 +/- 5 vs 357 +/- 4 b.p.m., respectively; P < 0.001). This baseline tachycardia was associated with a lower baroreflex sensitivity of the bradycardiac and tachycardiac responses in the bosentan-treated group compared with the control group. Sequential blockade of the parasympathetic and sympathetic autonomic nervous system with methylatropine and propranolol showed a higher intrinsic HR in the bosentan-treated group compared with the control group (411 +/- 5 vs 381 +/- 4 b.p.m., respectively; P < 0.05). This was accompanied by a higher cardiac sympathetic tone (31 +/- 1 vs 13 +/- 1%, respectively; P < 0.01) and a lower vagal parasympathetic tone (69 +/- 2 vs 87 +/- 2%, respectively; P < 0.01) in the bosentan-treated group compared with the control group. Variance and high-frequency oscillations of pulse interval (PI) variability in absolute and normalized units were lower in the bosentan-treated group than in the control group. Conversely, low-frequency (LF) oscillations of PI variability in absolute and normalized units, as well as variance and LF oscillations of systolic arterial pressure variability, were greater in the bosentan-treated group than the control group. 4. Overall, the data indicate an increased cardiac sympathetic drive, as well as lower vagal parasympathetic activity and baroreflex sensitivity, in conscious rats after chronic blockade of ET receptors with bosentan.     

Therapeutic administration of KM+ lectin protects mice against Paracoccidioides brasiliensis infection via interleukin-12 production in a toll-like receptor 2-dependent mechanism

KM(+) is a mannose-binding lectin from Artocarpus integrifolia that induces interleukin (IL)-12 production by macrophages and protective T helper 1 immune response against Leishmania major infection. In this study, we performed experiments to evaluate the therapeutic activity of jackfruit KM(+) (jfKM(+)) and its recombinant counterpart (rKM(+)) in experimental paracoccidioidomycosis. To this end, jfKM(+) or rKM(+) was administered to BALB/c mice 10 days after infection with Paracoccidiodes brasiliensis. Thirty days postinfection, lungs from the KM(+)-treated mice contained significantly fewer colony-forming units and little to no organized granulomas compared to the controls. In addition, lung homogenates from the KM(+)-treated mice presented higher levels of nitric oxide, IL-12, interferon-gamma, and tumor necrosis factor-alpha, whereas higher levels of IL-4 and IL-10 were detected in the control group. With mice deficient in IL-12, Toll-like receptor (TLR) 2, TLR4, or TLR adaptor molecule MyD88, we demonstrated that KM(+) led to protection against P. brasiliensis infection through IL-12 production, which was dependent on TLR2. These results demonstrated a beneficial effect of KM(+) on the severity of P. brasiliensis infection and may expand its potential use as a novel immunotherapeutic molecule.     

An Evaluation of Racial and Ethnic Health Differences in State Mental Health Inpatient Services: 2002–2005 Versus 2010–2011

This study analyzed racial-ethnic differences previously documented in the Connecticut Department of Mental Health and Addiction Services mental health inpatient system across two time periods (2002–2005 and 2010–2011). Comparisons of logistic regression analyses from the two time periods showed that, at time 1, significant racial-ethnic differences were found for referral by other sources (e.g., outpatient), length of stay, discharge against medical advice, and some diagnostic differences (e.g., schizophrenia, other psychotic disorders, cluster B discharge diagnosis), but these differences were not significant at time 2. Other diagnostic differences remained significant at time 2 (e.g., mood disorders, substance use disorders, other axis I disorders, mental retardation) as well as racial-ethnic differences in self-referral. These results suggest that the multiple national and state cultural competence initiatives between time 1 and time 2 could have resulted in decreases in racial-ethnic differences. Targeted interventions to alleviate the remaining differences are needed.