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Respiratory syncytial virus (RSV) infection is the leading cause of infant hospitalizations and mortality. Lumicitabine, an oral nucleoside analog was studied for the treatment of RSV. The phase 1b and phase 2b studies reported here assessed the safety, pharmacokinetics, and pharmacodynamics of lumicitabine in infants/neonates hospitalized with RSV. In the phase 1b study, infants (≥1 to ≤12 months) and neonates (<28 days) received a single-ascending or multiple-ascending doses (single loading dose [LD] then 9 maintenance doses [MD] of lumicitabine, or placebo [3:1]). In the phase 2b study, infants/children (28 days to ≤36 months old) received lumicitabine 40/20 mg/kg, 60/40 mg/kg LD/MD twice-daily or placebo (1:1:1) for 5 days. Safety, pharmacokinetics, and efficacy parameters were assessed over 28 days. Lumicitabine was associated with a dose-related increase in the incidence and severity of reversible neutropenia. Plasma levels of ALS-008112, the active nucleoside analog, were dose-proportional with comparable mean exposure levels at the highest doses in both studies. There were no significant differences between the lumicitabine groups and placebo in reducing viral load, time to viral non-detectability, and symptom resolution. No emergent resistance-associated substitutions were observed at the RSV L-gene positions of interest. In summary, lumicitabine was associated with a dose-related increase in the incidence and severity of reversible neutropenia and failed to demonstrate antiviral activity in RSV-infected hospitalized infants. This contrasts with the findings of the previous RSV-A adult challenge study where significant antiviral activity was noted, without incidence of neutropenia. Trial registration ClinicalTrials.gov Identifier: NCT02202356 (phase 1b); NCT03333317 (phase 2b).

Respiratory syncytial virus (RSV) infection is the leading cause of infant hospitalizations and mortality. Lumicitabine, an oral nucleoside analog was studied for the treatment of RSV. The phase 1b and phase 2b studies reported here assessed the safety, pharmacokinetics, and pharmacodynamics of lumicitabine in infants/neonates hospitalized with RSV. In the phase 1b study, infants ([greater than or equal to]1 to [less than or equal to]12 months) and neonates (<28 days) received a single-ascending or multiple-ascending doses (single loading dose [LD] then 9 maintenance doses [MD] of lumicitabine, or placebo [3:1]). In the phase 2b study, infants/children (28 days to [less than or equal to]36 months old) received lumicitabine 40/20 mg/kg, 60/40 mg/kg LD/MD twice-daily or placebo (1:1:1) for 5 days. Safety, pharmacokinetics, and efficacy parameters were assessed over 28 days. Lumicitabine was associated with a dose-related increase in the incidence and severity of reversible neutropenia. Plasma levels of ALS-008112, the active nucleoside analog, were dose-proportional with comparable mean exposure levels at the highest doses in both studies. There were no significant differences between the lumicitabine groups and placebo in reducing viral load, time to viral non-detectability, and symptom resolution. No emergent resistance-associated substitutions were observed at the RSV L-gene positions of interest. In summary, lumicitabine was associated with a dose-related increase in the incidence and severity of reversible neutropenia and failed to demonstrate antiviral activity in RSV-infected hospitalized infants. This contrasts with the findings of the previous RSV-A adult challenge study where significant antiviral activity was noted, without incidence of neutropenia.

Introduction: Worldwide public health authorities report 500,000 cases of invasive meningococcal disease with 50,000 deaths per year and 10-15% of sequelae in people affected. This study describes the epidemiology, microbiology, and clinical presentation of this disease in the Panamanian pediatric population. Methodology:  The discharge of patients with a meningococcal invasive disease diagnosis was reviewed in the statistical database and archives of the Hospital del Niño. Results: A total of 32 discharges with a meningococcal disease diagnosis were reported during the study period (1998-2008).  Ninety-one percent (n/N = 29/32) were confirmed as meningitis. The mean age of patients was 4.1 ± 4.6 years. The incidence in the period of the study was 0.25/100,000. Infants younger than one year old presented the highest incidence rate and number of cases. Four deaths were reported, three of which occurred in the group of 10-14 years and one in the group of 1-4 years. The overall fatality rate was 12.5%. The serogroup of the causative agent, Neisseria meningitidis, was documented in 30 of the 32 cases, with serogroup B the most frequent (66.7%). Ninety-percent (18/20) of serogroup B were isolated in the first five years of study. Serogroup C was identified in 8 of the 12 cases during the period 2004-2008. Conclusions: The present study showed a change in the epidemiological circulation pattern from serogroup B to serogroup C during the study period. Such epidemiological surveillance data is important in the implementation of preventive measures such as vaccination.

We evaluated the added value of collecting both nasal and oropharyngeal swabs, compared with collection of nasal swabs alone, for detection of common respiratory viruses by reverse transcription-polymerase chain reaction in hospitalized children aged <10 years. Nasal swabs had equal or greater sensitivity than oropharyngeal swabs for detection of respiratory syncytial virus, adenovirus, human metapneumovirus, rhinovirus, and influenza virus but not parainfluenza virus. The addition of an oropharyngeal swab, compared with use of a nasal swab alone, increased the frequency of detection of each respiratory virus by no more than 10% in children aged <10 years.

We assessed EV‐D68 epidemiology and phylogenetics among children aged ≤9 years hospitalized with severe acute respiratory illnesses at five sites in Panama and El Salvador during 2012‐2013. Respiratory specimens positive for enterovirus or rhinovirus were tested by real‐time RT‐PCR for EV‐D68, and partial VP1 gene sequences were determined. Of 715 enrolled children, 17 from sites in both countries were EV‐D68‐positive and commonly had a history of asthma or wheezing. Phylogenetically, 15 of 16 sequences fell into Clade B1, and one into Clade A2. The Central American EV‐D68s were closely related genetically to contemporaneous strains from North America, South America, and the Caribbean.