RESUMEN
Candida infections represent a major threat in neonatal intensive care units. This is the first prospective study to obtain caspofungin plasma levels and safety data for neonates and very young infants. Patients of <3 months of age receiving intravenous amphotericin B for documented or highly suspected candidiasis were enrolled in a single-dose (n = 6) or subsequent multiple-dose (n = 12) panel; all received caspofungin at 25 mg/m(2) once daily as a 1-hour infusion. Caspofungin plasma levels were measured by high-performance liquid chromatography and compared to historical data from adults. Patient chronological ages ranged from 1 to 11 weeks, and weights ranged from 0.68 to 3.8 kg. Gestational ages ranged from 24 to 41 weeks. Geometric mean (GM) peak (C(1 h)) and trough (C(24 h)) caspofungin levels were 8.2 and 1.8 microg/ml, respectively, on day 1, and 11.1 and 2.4 microg/ml, respectively, on day 4. GM ratios for C(1 h) and C(24 h) for neonates/infants relative to adults receiving caspofungin at 50 mg/day were 1.07 and 1.36, respectively, on day 1, and 1.18 and 1.21, respectively, on day 4. Clinical and laboratory adverse events occurred in 17 (94%) and 8 (44%) patients, respectively. Five patients (28%) had serious adverse events, none of which were considered drug related. Caspofungin at 25 mg/m(2) once daily was well tolerated in this group of neonates/infants of <3 months of age and appears to provide relatively similar plasma exposure to that obtained in adults receiving 50 mg/day. However, the small number of patients studied precludes any definitive recommendations about caspofungin dosing for this group comprising a broad range of ages and weights.
Asunto(s)
Antifúngicos/farmacocinética , Equinocandinas/farmacocinética , Antifúngicos/administración & dosificación , Antifúngicos/efectos adversos , Antifúngicos/sangre , Superficie Corporal , Candidiasis/tratamiento farmacológico , Caspofungina , Ensayos Clínicos como Asunto , Esquema de Medicación , Equinocandinas/administración & dosificación , Equinocandinas/efectos adversos , Equinocandinas/sangre , Femenino , Fiebre/inducido químicamente , Humanos , Hipertensión/inducido químicamente , Hiperventilación/inducido químicamente , Lactante , Recién Nacido , Infusiones Intravenosas , Lipopéptidos , Masculino , Estudios Multicéntricos como Asunto , Estudios ProspectivosRESUMEN
The study was planned to assess and compare the immune response and safety of an indigenous DTPwHB-Hib pentavalent liquid combination vaccine (Shan 5) with Easyfive and TritanrixHB+ Hiberix, the two available pentavalent combination vaccines. Four hundred infants were randomized to receive three doses of either Shan 5 or one of the two comparators. Antibody analysis was performed prior to and four to six weeks post third vaccine dose. Solicited local and systemic events upto three days and unsolicited adverse events in the 30 days follow up period after each dose were recorded. A total of 365 subjects completed the study. Four to six weeks after third dose, 98.32% of the subjects in Shan 5 group had seroprotective Anti PRP-T IgG antibody concentrations (> or =0.15 microg/mL) as compared to 100% and 98.94% subjects in TritanrixHB + Hiberix and Easyfive groups respectively. Seroprotective levels for Anti-HBs (> or =10 mIU/mL) were observed in 97.77%, 97.83% and 98.94% subjects in Shan 5, TritanrixHB + Hiberix and Easyfive groups respectively. Comparable immune responses were observed for the three other components (D, T and P) in all the groups. Four Serious Adverse Events (SAEs) were reported (three with Shan 5 and one with Easyfive), all unrelated to the respective vaccines. Most commonly reported adverse events in all the groups were pain at injection site, mild fever (<103 degrees F) and minor swelling at injection site. The study proved that Shan 5 was safe and immunogenic compared to the two other licensed vaccines.
Asunto(s)
Vacuna contra Difteria, Tétanos y Tos Ferina/efectos adversos , Vacuna contra Difteria, Tétanos y Tos Ferina/inmunología , Vacunas contra Haemophilus/efectos adversos , Vacunas contra Haemophilus/inmunología , Vacunas contra Hepatitis B/efectos adversos , Vacunas contra Hepatitis B/inmunología , Anticuerpos Antibacterianos/sangre , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Femenino , Fiebre/inducido químicamente , Anticuerpos contra la Hepatitis B/sangre , Humanos , Inmunización Secundaria/métodos , Inmunoglobulina G/sangre , India , Lactante , Masculino , Dolor/inducido químicamente , Enfermedades de la Piel/inducido químicamente , Enfermedades de la Piel/patologíaRESUMEN
Hand foot and mouth disease (HFMD) is a relatively unreported disease in India. This study was undertaken to characterize the enterovirus type/s associated with two unexpectedly-massive epidemics that occurred in Bangalore, India in 2013 and 2015. Stool samples of 229 children with HFMD living in Northern and Southern areas of Bangalore were tested by RT-PCR; 189 (82.5%) were enterovirus positive. The Indian CV-A16 strains exhibited 98-99% sequence identity with those reported in France and China in the 5' untranslated region. BLAST and phylogenetic analyses of complete genomes of representative Indian isolates revealed that the 2015 epidemic was predominated by an inter-species recombinant between CV-A16 and coxsackievirus B5. The 2013 epidemic was primarily caused by nonrecombinant strains. The CV-A16 strains circulated in India since 2007 and phylogeographic analyses indicated imported cases in France and China. In conclusion, CV-A16-associated HFMD epidemics should be recognized as an emerging public health problem in India.
Asunto(s)
Brotes de Enfermedades , Enterovirus , Enfermedad de Boca, Mano y Pie/epidemiología , Enfermedad de Boca, Mano y Pie/virología , Regiones no Traducidas 5' , Teorema de Bayes , Epidemias , Evolución Molecular , Genoma Viral , Enfermedad de Boca, Mano y Pie/historia , Historia del Siglo XXI , Humanos , India/epidemiología , Filogenia , Vigilancia de la Población , ARN Viral , Recombinación Genética , Análisis de Secuencia de ARN , Análisis Espacial , Secuenciación Completa del GenomaRESUMEN
BACKGROUND: We recently reported significant association of non-polio enteroviruses (NPEVs) with acute diarrhea in children. Persistent diarrhea (PD) remains a major cause of morbidity and mortality in infants below two years of age in developing countries. Understanding age-dependent frequency and duration of NPEV infections is important to determine their association with persistent diarrhea and disease burden. OBJECTIVES: A cohort of 140 infants was followed for 6 months to 2 years of age to determine the frequency, duration, and association with PD of NPEV infections in comparison with rotavirus and other agents. STUDY DESIGN: Stool samples were collected every 14 days, and diarrheal episodes and their duration were recorded. Enteroviruses were characterized by RT-PCR and VP1 gene sequence analysis, rotavirus by electropherotyping, and other agents by PCR. RESULTS: Of 4545 samples, negative for oral polio vaccine strains, 3907 (85.96%) and 638 (14.04%) were NPEV-negative and NPEV-positive, respectively, representing 403 (8.87%) infection episodes. About 68% of NPEV infections occurred during the first year with every child having at least one episode lasting between four days and four months. Approximately 38% and 22% of total diarrheal episodes were positive for NPEV and RV, respectively. While about 18% of NPEV infection episodes were associated with diarrhea, 6% being persistent, 13% of total diarrheal episodes were persistent involving infections by monotype NPEV strains or sequential infections by multiple strains and other agents. CONCLUSIONS: This is the first report revealing NPEVs as the single most frequently and persistently detected viral pathogen in every PD episode.