Immune response profiles from humans experimentally exposed to Phlebotomus duboscqi bites.

Introduction: Cutaneous leishmaniasis is a neglected vector-borne parasitic disease prevalent in 92 countries with approximately one million new infections annually. Interactions between vector saliva and the human host alter the response to infection and outcome of disease. Methods: To characterize the human immunological responses developed against saliva of Phlebotomus duboscqi, a Leishmania major (L. major) vector, we repeatedly exposed the arms of 14 healthy U.S volunteers to uninfected P. duboscqi bites. Blood was collected a week after each exposure and used to assess total IgG antibodies against the proteins of P. duboscqi salivary gland homogenate (SGH) and the levels of IFN-gamma and IL-10 from peripheral blood mononuclear cells (PBMCs) stimulated with SGH or recombinant sand fly proteins. We analyzed skin punch biopsies of the human volunteer arms from the insect bite site and control skin site after multiple P. duboscqi exposures (four volunteers) using immunohistochemical staining. Results: A variety of immediate insect bite skin reactions were observed. Late skin reactions to insect bites were characterized by macular hyperpigmentation and/or erythematous papules. Hematoxylin and eosin staining showed moderate mononuclear skin infiltrate with eosinophils in those challenged recently (within 2 months), eosinophils were not seen in biopsies with recall challenge (6 month post bites). An increase in plasma antigen-specific IgG responses to SGH was observed over time. Western Blot results showed strong plasma reactivity to five P. duboscqi salivary proteins. Importantly, volunteers developed a cellular immunity characterized by the secretion of IFN-gamma upon PBMC stimulation with P. duboscqi SGH and recombinant antigens. Discussion: Our results demonstrate that humans mounted a local and systemic immune response against P. duboscqi salivary proteins. Specifically, PduM02/SP15-like and PduM73/adenosine deaminase recombinant salivary proteins triggered a Th1 type immune response that might be considered in future development of a potential Leishmania vaccine.

A randomized controlled trial of local heat therapy versus intravenous sodium stibogluconate for the treatment of cutaneous Leishmania major infection.

BACKGROUND: Cutaneous Leishmania major has affected many travelers including military personnel in Iraq and Afghanistan. Optimal treatment for this localized infection has not been defined, but interestingly the parasite is thermosensitive. METHODOLOGY/PRINCIPAL FINDINGS: Participants with parasitologically confirmed L. major infection were randomized to receive intravenous sodium stibogluconate (SSG) 20mg/kg/day for ten doses or localized ThermoMed (TM) device heat treatment (applied at 50 degrees C for 30 seconds) in one session. Those with facial lesions, infection with other species of Leishmania, or more than 20 lesions were excluded. Primary outcome was complete re-epithelialization or visual healing at two months without relapse over 12 months. Fifty-four/56 enrolled participants received intervention, 27 SSG and 27 TM. In an intent to treat analysis the per subject efficacy at two months with 12 months follow-up was 54% SSG and 48% TM (p = 0.78), and the per lesion efficacy was 59% SSG and 73% TM (p = 0.053). Reversible abdominal pain/pancreatitis, arthralgias, myalgias, headache, fatigue, mild cytopenias, and elevated transaminases were more commonly present in the SSG treated participants, whereas blistering, oozing, and erythema were more common in the TM arm. CONCLUSIONS/SIGNIFICANCE: Skin lesions due to L. major treated with heat delivered by the ThermoMed device healed at a similar rate and with less associated systemic toxicity than lesions treated with intravenous SSG. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT 00884377.

The effect of intranasal administration of remifentanil on intubating conditions and airway response after sevoflurane induction of anesthesia in children.

BACKGROUND: Intubation without the use of muscle relaxants in children is frequently done before IV access is secured. In this randomized controlled trial, we compared intubating conditions and airway response to intubation (coughing and/or movement) after sevoflurane induction in children at 2 and 3 min after the administration of intranasal remifentanil (4 mcg/kg) or saline. METHODS: One hundred eighty-eight children, 1-7-yr old, were studied. Nasal remifentanil (4 mcg/kg) or saline was administered 1 min after an 8% sevoflurane N2O induction. The sevoflurane concentration was then reduced to 5% in oxygen, and ventilation assisted/controlled. An anesthesiologist blinded to treatment assignment used a validated score to evaluate the conditions for laryngoscopy and response to intubation. Blood samples for determination of remifentanil blood concentrations were collected from 17 children at baseline, 2, 3, 4, and 10 min after nasal administration of remifentanil. RESULTS: Good or excellent intubating conditions were achieved at 2 min (after the remifentanil bolus) in 68.2% and at 3 min in 91.7% of the children who received intranasal remifentanil versus 37% and 23% in children who received placebo (P<0.01). The mean remifentanil plasma concentrations (+/-sd) at 2, 3, 4, and 10 min were 1.0 (0.60), 1.47 (0.52), 1.70 (0.46), and 1.16 (0.36) ng/mL, respectively. Peak plasma concentration was observed at 3.47 min. There were no complications associated with the use of nasal remifentanil. CONCLUSIONS: Nasal administration of remifentanil produces good-to-excellent intubating conditions in 2-3 min after sevoflurane induction of anesthesia.

Ondansetron oral disintegrating tablets: acceptability and efficacy in children undergoing adenotonsillectomy.

Postoperative nausea and vomiting (PONV), a major complication in children, is responsive to IV and oral ondansetron. Because these routes are not always available, we studied the acceptability and efficacy of ondansetron oral disintegrating tablets (ODT). In this double-blind, randomized, placebo-controlled study, 62 patients undergoing adenotonsillectomy, aged 5 to 11 years, preoperatively received ODT (4 mg) or placebo. Patients assessed the medication for taste and sensation. Anesthesia was induced with sevoflurane, maintained with desflurane, and supplemented with fentanyl 2.5 microg/kg and dexamethasone 0.5 mg/kg (maximum dose, 12 mg). An observer blinded to treatment evaluated patients for pain, agitation, and PONV. Postoperative treatment consisted of fentanyl 1 microg/kg for pain and agitation and metoclopramide 0.15 mg/kg (maximum dose, 10 mg) for PONV. There were no significant differences between study groups with regard to age, weight, recovery time, agitation, or pain. Approximately 90% of the subjects found the ODT to taste good. No subject rejected the study medication, but the ondansetron-containing tablets were found to be less palatable than the placebo. The incidence of vomiting was significantly less in the ondansetron-medicated group.

Rapid emergence does not explain agitation following sevoflurane anaesthesia in infants and children: a comparison with propofol.

BACKGROUND: Emergence agitation in children is frequently associated with the use of the new highly insoluble volatile anaesthetics. Rapid emergence has been cited as one of the possible causes. Propofol also permits rapid emergence from general anaesthesia but is not associated with agitation. METHODS: The emergence characteristics of children receiving sevoflurane and propofol anaesthesia were examined. After induction with sevoflurane, 53 children, aged 2-36 months, who were undergoing ambulatory surgery, were randomized to receive maintenance anaesthesia with either sevoflurane or propofol. Introperative analgesia with either 2 micro g x kg-1 of intravenous fentanyl or a caudal block with 0.25% bupivacaine was supplied according to surgical procedure. An observer blinded to anaesthetic technique recorded the time to achieve extubation and recovery and assessed emergence behaviour. Data were analysed using Wilcoxon scores, Kruskal-Wallis test, chi-square and multiple regression analysis. RESULTS: The results showed that the time to extubation and recovery were similar between the two study groups, but that emergence agitation was significantly higher in the sevoflurane group compared with the propofol group. No relationship between analgesic technique and agitation scores was found. CONCLUSIONS: Although both sevoflurane and propofol allow for rapid emergence from general anaesthesia, only sevoflurane is associated with a high incidence of emergence agitation in infants and young children. Rapid emergence does not fully explain this phenomena.

The effect of fentanyl on the emergence characteristics after desflurane or sevoflurane anesthesia in children.

UNLABELLED: Desflurane and sevoflurane anesthesia are associated with emergence agitation in children. In this study, we examined the effect of a single intraoperative dose of fentanyl on emergence characteristics in children undergoing adenoidectomy. One hundred children, 2-7 yr old, were randomly assigned to receive desflurane or sevoflurane for maintenance of general anesthesia after an inhaled induction with sevoflurane and a 2.5 microg/kg dose of fentanyl. An observer blind-ed to the anesthetic technique assessed the times to achieve emergence, extubation and recovery criteria, as well as emergence behaviors. The results showed a similar incidence of severe emergence agitation after general anesthesia with desflurane (24%) and sevoflurane (18%). Times to achieve extubation and postanesthesia care unit discharge criteria were shorter with desflurane than with sevoflurane. With this technique, desflurane allows for a more rapid emergence and recovery than sevoflurane. In children receiving desflurane or sevoflurane, the concurrent use of fentanyl in a dose of 2.5 microg/kg results in a small incidence of emergence agitation. IMPLICATIONS: The concurrent use of fentanyl in a dose of 2.5 microg/kg in children receiving desflurane or sevoflurane results in a low incidence of emergence agitation. Desflurane allows for a more rapid emergence and recovery than sevoflurane.

A comparison of three doses of a commercially prepared oral midazolam syrup in children.

UNLABELLED: Midazolam is widely used as a preanesthetic medication for children. Prior studies have used extemporaneous formulations to disguise the bitter taste of IV midazolam and to improve patient acceptance, but with unknown bioavailability. In this prospective, randomized, double-blinded study we examined the efficacy, safety, and taste acceptability of three doses (0.25, 0.5, and 1.0 mg/kg, up to a maximum of 20 mg) of commercially prepared Versed((R)) syrup (midazolam HCl) in children stratified by age (6 mo to <2 yr, 2 to <6 yr, and 6 to <16 yr). All children were ASA class I-III scheduled for elective surgery. Subjects were continuously observed and monitored with pulse oximetry. Ninety-five percent of patients accepted the syrup, and 97% demonstrated satisfactory sedation before induction. There was an apparent relationship between dose and onset of sedation and anxiolysis (P < 0.01). Eight-eight percent had satisfactory anxiety ratings at the time of attempted separation from parents, and 86% had satisfactory anxiety ratings at face mask application. The youngest age group recovered earlier than the two older age groups (P < 0.001). There was no relationship between midazolam dose and duration of postanesthesia care unit stay. Before induction, there were no episodes of desaturation, but there were two episodes of nausea and three episodes of emesis. At the time of induction, during anesthesia, and in the postanesthesia care unit, there were several adverse respiratory events. Oral midazolam syrup is effective for producing sedation and anxiolysis at a dose of 0.25 mg/kg, with minimal effects on respiration and oxygen saturation even when administered at doses as large as 1.0 mg/kg (maximum, 20 mg) as the sole sedating medication to healthy children in a supervised clinical setting. IMPLICATIONS: Commercially prepared oral midazolam syrup is effective in producing sedation and anxiolysis in doses as small as 0.25 mg/kg; there is a slightly faster onset with increasing the dose to 1.0 mg/kg. At all doses, 97% of patients demonstrated satisfactory sedation, whereas 86% demonstrated satisfactory anxiolysis when the face mask was applied.