Calil Kairalla Farhat

Efficacy and safety of 1 and 2 doses of live attenuated influenza vaccine in vaccine-naive children.

Background: We investigated the efficacy and safety of 1 versus 2 doses of live attenuated influenza vaccine (LAIV) in influenza vaccine–naive children aged 6 to <36 months. Patients/Methods: Subjects were randomized to 1 of 4 regimens in year 1: 2 doses LAIV, 1 dose LAIV, excipient placebo, or saline placebo. In year 2, LAIV recipients were to receive 1 dose of LAIV and placebo recipients were to receive saline placebo. Because of an unintended treatment allocation error in year 2, 1 block of subjects who were randomized to LAIV received saline placebo and 1 block who were randomized to placebo received LAIV. Results: In year 1, vaccine efficacy versus placebo among recipients of 2 and 1 doses of LAIV was 73.5% and 57.7%, respectively, against antigenically similar strains. In year 2, absolute efficacy of a single dose of LAIV was 73.6% and 65.2%, respectively, in recipients of 2 and 1 doses of LAIV in year 1. Year 2 efficacy was 57.0% in subjects who received 2 doses of LAIV in year 1 and placebo in year 2. Safety and tolerability of LAIV were consistent with previous studies. Reactogenicity was similar between placebo groups. Seroconversion rates were significantly higher in the 2-dose versus the 1-dose LAIV group in year 1 and in both LAIV groups versus placebo in years 1 and 2. Conclusions: One dose of LAIV provided clinically significant protection against influenza in young children previously unvaccinated against influenza; 2 doses provided additional protection. Protection after 2 doses in year 1 persisted through a second season without revaccination. LAIV excipients were not a major contributor to reactogenicity. These benefits provide support for increased use of LAIV in children ≥2 years of age.

Clinical presentation and follow up of children with congenital toxoplasmosis in Brazil

We evaluated the clinical presentation and determined the ocular and neurologic sequelae in children with congenital toxoplasmosis in Brazil, taking into consideration the shortage of national publications on this disease. Follow-up evaluations were made of 43 children with congenital toxoplasmosis referred to Santa Casa de São Paulo, during a period of at least five years. Selection of the cases was based in clinical and laboratory criteria. A clear predominance of children with subclinical presentation of the disease at birth (88%) was found. Of the 43 children, 22 (51%) developed neurological manifestations. Using skull radiography, we detected neuroradiologic alterations in seven children (16%) and with tomography in 33 children (77%). Neurological sequelae were identified in 15 children (54%) in the group with cerebral calcifications and in 7 (47%) in the group without cerebral calcifications. We observed chorioretinitis in 95% of the cases. Reactivation of cicatricial lesions and the emergence of new ocular lesions were observed in five cases. The most frequent neurological manifestation was a delay in neuropsychomotor development. Most remarkable was the finding that cerebral calcifications were not associated with a higher incidence of neurological sequelae among the children. Chorioretinitis was the main ocular sequel of the infection, found in nearly all children; it can manifest years from birth, even in children submitted to specific therapy druing the first year of life, highlighting the importance of a follow-up of these children.

Maternal and infant antibody response to meningococcal vaccination in pregnancy.

The antigenic capacity of a mixed vaccine prepared with polysaccharides of meningococcus groups A and C, the placental transfer of antibodies, and the persistence of positive titres in the infant were evaluated in 21 pregnant women and their offspring during an epidemic of meningitis in São Paulo, Brazil; and antibody response was assessed in 29 infants vaccinated at less than 6 months of age. Antibodies were detected by passive haemagglutination; the high titres found and the high frequency of positive results are thought to be due to the use of a more sensitive technique. Increased antibody titres were found in most women, and there was evidence for passive transfer to the newborn, especially with regard to antibody type C. However, passive transfer was irregular, and the presence of antibodies in the mother did not guarantee their presence in the child. Passive transfer lasted for only 2-5 months. Vaccination in children under 6 months of age had poor results; only 1 child seroconverted.

Seroprevalence of herpes simplex 1-2 antibodies in Brazil

OBJETIVO: Estimar la seroprevalencia de anticuerpos por virus herpes simples (HSV-1 y HSV-2) en diferentes areas geograficas en Brasil y analizar factores asociados. METODOS: Estudio transversal realizado entre 1996 y 1997 con individuos de la poblacion en general en cuatro diferentes areas geograficas en Brasil y estratificados por edad (de uno a 40 anos) y sexo, de los cuales 1.090 fueron incluidos en el analisis final. Fueron analizadas muestras de sangre para deteccion de anticuerpos para HSV-1 y HSV-2 con prueba tipo-especifica ELISA gG1-gG2. Fueron descritas frecuencias y proporciones y comparadas entre grupos utilizando la prueba de Fisher bilateral exacta. Fue realizado analisis de regresion logistica para evaluar influencia de las variables edad, sexo, geografia, grupo economico, historico de DST, seropositividad para anti-HSV-1 o anti-HSV-2 e interacciones de cualquiera de esos factores sobre la seroprevalencia de HSV-1 y/o HSV-2. RESULTADOS: La tasa de seroprevalencia de anticuerpos para HSV-1 ajustada por edad fue de 67,2%, sin diferencia con relacion al sexo, siendo mayor en la Region Norte. Las seroprevalencias aumentaron con la edad, y para HSV-2, hube un aumento significativo en la adolescencia y entre adultos jovenes. Individuos seropositivos para HSV-1 presentaron mayor riesgo de ser positivos para HSV-2 (15,7%) cuando se compararon con los negativos para HSV-1 (4,7%). En el analisis multivariado, el historico de DST aumento significativamente (OR=3,2) la probabilidad de seropositividad para HSV-2. CONCLUSIONES: Las seroprevalencias para HSV-1 y para HSV-2 varian con la edad y presentan diferencias significativas entre las regiones de Brasil. Historia anterior de DST es importante factor de riesgo para adquisicion de infeccion por HSV-2.OBJECTIVE To estimate the seroprevalence of HSV-1 and HSV-2 antibodies in Brazil and to analyze factors associated. METHODS Cross-sectional study including subjects aged 1-40 years from the general population in four different geographical areas in Brazil between 1996 and 1997. All subjects were stratified by age and gender and 1,090 of them were included in the final analysis. Blood samples were tested for HSV-1 and HSV-2 antibodies by type-specific (gG1 and gG2) ELISA. Frequencies and proportions were described and compared among groups using two-sided Fishers exact test. A logistic regression analysis was performed to assess the influence of the variables age, gender, geographical area, socioeconomic condition, past history of STD, seropositivity for anti-HSV-1 or anti-HSV-2 and interactions of any of these factors on the seroprevalence of HSV-1 and/or HSV-2. RESULTS The age-adjusted seroprevalences of HSV-1 and HSV-2 antibodies were 67.2% and 11.3%, respectively, without sex differences and being higher in the North region. Seroprevalences increased with age and, for HSV-2 infection, the higher increase was observed among adolescents and young adults. Subjects who tested positive for HSV-1 were more likely to also test positive for HSV-2 (15.7%) compared to HSV-1 negative subjects (4.7%). In the multivariate analysis past history of STD significantly (OR=3.2) increased the likelihood of HSV-2 infection whereas socioeconomic condition did not affect the results. CONCLUSIONS HSV-1 and HSV-2 seroprevalences vary with age and among Brazilian regions. Past history of STD is a major risk factor for HSV-2 infection.

Uso de diagramas de controle na vigilância epidemiológica das infecções hospitalares

OBJECTIVE To monitor occurrence trends and identify clusters of nosocomial infection (NI) using statistical process control (SPC) charts. METHODS Between January 1998 and December 2000 nosocomial infection occurrence was evaluated in a cohort of 460 patients admitted to the Pediatric Intensive Care Unit of a university hospital, according to the concepts and criteria proposed by the National Nosocomial Infection Surveillance System of the Centers for Disease Control, in the United States. Graphs were plotted using Poisson statistical distribution, including four horizontal lines: center line (CL), upper warning limit (UWL) and upper control limit (UCL). The CL was the arithmetic mean NI rate calculated for the studied period; UWL and UCL were drawn at 2 and 3 standard deviations above average NI rates, respectively. Clusters were identified when NI rates remained above UCL. RESULTS Mean NI incidence was 20 per 1,000 patient days. One urinary tract infection cluster was identified in July 2000, with an infection rate of 63 per 1,000 patient days, exceeding UCL and characterizing a period of epidemic. CONCLUSIONS The use of SPC charts for controlling endemic levels of NI, through both global and site-specific evaluation, allowed for the identification of uncommon variations in NI rates, such as outbreaks and epidemics, and for their distinction from the natural variations observed in NI occurrence rates, without the need for calculations and hypothesis testing.

Soroprevalência de anticorpos contra vírus herpes simples 1-2 no Brasil

OBJETIVO: Estimar la seroprevalencia de anticuerpos por virus herpes simples (HSV-1 y HSV-2) en diferentes areas geograficas en Brasil y analizar factores asociados. METODOS: Estudio transversal realizado entre 1996 y 1997 con individuos de la poblacion en general en cuatro diferentes areas geograficas en Brasil y estratificados por edad (de uno a 40 anos) y sexo, de los cuales 1.090 fueron incluidos en el analisis final. Fueron analizadas muestras de sangre para deteccion de anticuerpos para HSV-1 y HSV-2 con prueba tipo-especifica ELISA gG1-gG2. Fueron descritas frecuencias y proporciones y comparadas entre grupos utilizando la prueba de Fisher bilateral exacta. Fue realizado analisis de regresion logistica para evaluar influencia de las variables edad, sexo, geografia, grupo economico, historico de DST, seropositividad para anti-HSV-1 o anti-HSV-2 e interacciones de cualquiera de esos factores sobre la seroprevalencia de HSV-1 y/o HSV-2. RESULTADOS: La tasa de seroprevalencia de anticuerpos para HSV-1 ajustada por edad fue de 67,2%, sin diferencia con relacion al sexo, siendo mayor en la Region Norte. Las seroprevalencias aumentaron con la edad, y para HSV-2, hube un aumento significativo en la adolescencia y entre adultos jovenes. Individuos seropositivos para HSV-1 presentaron mayor riesgo de ser positivos para HSV-2 (15,7%) cuando se compararon con los negativos para HSV-1 (4,7%). En el analisis multivariado, el historico de DST aumento significativamente (OR=3,2) la probabilidad de seropositividad para HSV-2. CONCLUSIONES: Las seroprevalencias para HSV-1 y para HSV-2 varian con la edad y presentan diferencias significativas entre las regiones de Brasil. Historia anterior de DST es importante factor de riesgo para adquisicion de infeccion por HSV-2.OBJECTIVE To estimate the seroprevalence of HSV-1 and HSV-2 antibodies in Brazil and to analyze factors associated. METHODS Cross-sectional study including subjects aged 1-40 years from the general population in four different geographical areas in Brazil between 1996 and 1997. All subjects were stratified by age and gender and 1,090 of them were included in the final analysis. Blood samples were tested for HSV-1 and HSV-2 antibodies by type-specific (gG1 and gG2) ELISA. Frequencies and proportions were described and compared among groups using two-sided Fishers exact test. A logistic regression analysis was performed to assess the influence of the variables age, gender, geographical area, socioeconomic condition, past history of STD, seropositivity for anti-HSV-1 or anti-HSV-2 and interactions of any of these factors on the seroprevalence of HSV-1 and/or HSV-2. RESULTS The age-adjusted seroprevalences of HSV-1 and HSV-2 antibodies were 67.2% and 11.3%, respectively, without sex differences and being higher in the North region. Seroprevalences increased with age and, for HSV-2 infection, the higher increase was observed among adolescents and young adults. Subjects who tested positive for HSV-1 were more likely to also test positive for HSV-2 (15.7%) compared to HSV-1 negative subjects (4.7%). In the multivariate analysis past history of STD significantly (OR=3.2) increased the likelihood of HSV-2 infection whereas socioeconomic condition did not affect the results. CONCLUSIONS HSV-1 and HSV-2 seroprevalences vary with age and among Brazilian regions. Past history of STD is a major risk factor for HSV-2 infection.

S. pneumoniae isolados da nasofaringe de crianças sadias e com pneumonia: taxa de colonização e suscetibilidade aos antimicrobianos

OBJECTIVES To compare colonization rates and antimicrobial resistance of nasopharyngeal pneumococci in healthy carriers and children with pneumonia. METHODS A cross-sectional study. Healthy subjects of this study were selected from randomly chosen immunization centers and day-care centers, and those with pneumonia were selected in pediatric emergency rooms. Flexible perinasal alginate swabs were employed to collect nasopharyngeal pneumococci specimens. Isolation and identification were performed according to standard procedures. Minimum Inhibitory Concentrations were assessed by microdilution techniques. RESULTS We studied 911 children, 429 healthy controls (60% of carriers, 72% attending day care centers and 49% recruited in immunization centers) and 482 children with pneumonia (50% of carriers) (P=0.02). The Minimum Inhibitory Concentration of penicillin to 441 isolates detected 198 (45%) of intermediate and 16 (4%) fully resistant pneumococci. Antimicrobial resistance rates of isolates from healthy carriers and children with pneumonia were, respectively: penicillin 48% (37% for immunization centers and 55% for day-care centers) and 50% (P>0.05), erythromycin 28% and 19% (P=0.05); cotrimoxazole 81% and 76% (P>0.05), chloramphenicol 6% and 7% (P>0.05), rifampin 5 and 3% (P>0.05) ceftriaxone 2 and 4% (P>0.05) and vancomycin 0% in both groups. An association among pneumococcal resistance to penicillin, erythromycin and cotrimoxazole was detected. CONCLUSIONS Pneumococcal carriage rate was higher in healthy children than in children with pneumonia. Penicillin and cotrimoxazole resistance rates were high, especially among those attending day-care centers.

Antimicrobial susceptibility and serotypes of nasopharyngeal Streptococcus pneumoniae in children with pneumonia and in children attending day-care centres in Fortaleza, Brazil.

The susceptibility of nasopharyngeal Streptococcus pneumoniae to eight antibiotics was studied in 482 children under 5 years of age with community-acquired pneumonia and in 429 healthy pneumococci carriers in Fortaleza, Brazil. Serotyping of strains with pooled and type-specific antisera was also performed. Overall, S. pneumoniae was isolated from 499/911 (55%) children. The carriage rate in children attending day-care centres was higher (72%) than in children with pneumonia (50%) (P<0.001). MIC determination in 441 strains revealed 45% to be intermediate penicillin-resistant and 4% high penicillin-resistant strains. Resistance rates to co-trimoxazole and erythromycin were 42 and 23%, respectively. Serotyping of 211 penicillin-resistant and 58 randomly selected penicillin-susceptible isolates showed that 78% of the strains belonged to paediatric serogroups 6, 14, 19 and 23 (86% of the penicillin-resistant and 51% of the penicillin-susceptible strains, P=0.001). Resistance rates of S. pneumoniae to penicillin and co-trimoxazole in Fortaleza were higher than previously reported in Brazil and associated with paediatric serogroups 6, 14, 19 and 23.

Seroconversion of a trivalent measles, mumps, and rubella vaccine in children aged 9 and 15 months

The serological response to MMR vaccine was evaluated in 109 9-month-old infants having no history of measles vaccination, and in 98 15-month-old children who had received monocomponent measles immunisation at 9 months. The combined vaccine contained Schwarz, Urabe Am9, and Wistar RA 27/3 live attenuated virus strains. Preimmunisation antibody levels were extremely low for the 9-month-old children, indicating that maternally-transmitted antibodies do not persist at this age. In the case of mumps, preimmunisation antibody levels were significantly higher in the 15-month-old than in the 9-month-old group. A difference between groups in terms of postimmunisation antibody titres was observed only for rubella, with titres being significantly higher in the older group. Seroconversion rates were high in both groups and no serious events attributable to vaccination were observed. The MMR vaccine can thus be administered to children as young as 9 months of age. Evidence for the efficacy of a two-dose schedule, i.e. at 9 and 15 months, is presented.

Pediatric Risk of mortality and hospital infection

We studied the association of Pediatric Risk of Mortality scores with nosocomial infections among 341 critically ill patients admitted to a pediatric intensive care unit between June 1998 and December 2000. Through stepwise logistic regression analysis, the best predictors for nosocomial infections were device utilization ratio, antimicrobial therapy, and length of stay.