Maria Del Valle Juarez

Impact of a maternal immunization program against pertussis in a developing country

BACKGROUND Pertussis disease is a growing concern for developing countries. In Argentina, rates of illness and death peaked in 2011. More than 50% of fatalities due to pertussis occurred in infants younger than two months of age, too young for vaccination. In 2012, the government offered immunization with a vaccine containing Tdap to all pregnant women after 20weeks of gestation with the intent of reducing morbidity and mortality in young infants. METHODS Maternal acellular pertussis vaccine impact on reducing infant disease burden was estimated based on data from the Argentinean Health Surveillance System. We divided Argentinean states in two groups experiencing high (>50) and low (⩽50) Tdap vaccine coverage and compared these two groups using a Bayesian structural time-series model. Low coverage regions were used as a control group, and the time series were compared before and after the implementation of the Tdap program. FINDINGS We observed a relative reduction of 51% (95% CI [-67%, -35%]; p=0.001) in pertussis cases in high coverage states in comparison with the low coverage areas. Analysis of infants between two and six months showed a 44% (95% CI [-66%, -24%]; p=0.001) reduction in illness. Number of deaths was highest in 2011 with 76 fatalities, for an incidence rate of 2.9 per 100,000. Comparing with 2011, rates decreased by 87% to 10 subjects, or 0.9 per 100,000 in 2013. INTERPRETATION We show an age-dependent protective effect of maternal Tdap immunization in a developing country for infants younger than six months.

Influenza vaccine: Delayed vaccination schedules and missed opportunities in children under 2 years old.

INTRODUCTION In Argentina respiratory disease is the third leading cause of death in children under 5 years. In 2011 influenza vaccination was included in the National Calendar for children between 6 and 24 months (two doses schedule). Influenza vaccine coverage for second dose was 46.1% in 2013. The aim was to determine the proportion of delayed schedules and missed opportunities, to assess the characteristics of missed opportunities for vaccination and to explore the perception of influenza disease and vaccination from the parents of children between 6 and 24 months in different regions of Argentina in 2013. METHODS Analytical observational multicenter cross-sectional study. Structured surveys were carried out to the childrens parents who were between 6 and 24 months of age during the influenza virus vaccination season (April-October 2013). Chi-Square test was used to assess association and differences between proportions and categorical variables. A logistic regression model was built to identify delay predictor variables in the vaccination schedules. Missed opportunities for vaccination were characterized through the estimation of proportions. RESULTS 1350 surveys were conducted in the three centers. We detected 65% (884/1340) of delayed influenza vaccination schedules, 97% of them associated with missed opportunities of vaccination. The independent protective factors associated with a decreases risk of delayed schedules were: (a) perception of the importance of influenza vaccination (OR=0.42(0.18-0.94); p=0.035), (b) having less than one year of age (OR=0.75(0.59-0.96); p=0.022), (c) to have received information in pediatric visits or in any media (OR=0.71(0.56-0.90); p=0.004). There was 38% of MOIV in 1st dose and 63.4% in 2nd dose. The main cause of MOIV in 1st dose was not detecting the need for vaccination (39%) and in 2nd dose the unknowledge of the vaccination schedule (35.3%). No cultural reasons were detected. CONCLUSIONS High frequency of delayed vaccination schedules and missed opportunities were detected. Parents had little concern about the safety of influenza vaccine.

Influence of respiratory viruses on the evaluation of the 13-valent pneumococcal conjugate vaccine effectiveness in children under 5 years old: A time-series study for the 2001-2013 period

INTRODUCTION S treptococcus pneumoniae is the main agent in bacterial consolidated pneumonias. In 2012, the 13-valent pneumococcal conjugate vaccine was introduced in the Argentine national immunization schedule for immunocompetent children as of two months old with a two-dose schedule plus a booster. OBJECTIVE To analyze the influence of respiratory viruses on the evaluation of the 13-valent pneumococcal conjugate vaccine effectiveness in relation to the number of hospitalizations for radiologically-confirmed consolidated pneumonias (RCCP). METHODS Observational, analytical, time-series study. All children hospitalized with a diagnosis of RCCP as per the World Health Organizations criteria between March and November throughout the2001-2013period were included. Viral diagnosis (respiratory syncytial virus, adenovirus, influenza and parainfluenza) was performed by indirect immunofluorescence using nasopharyngeal aspirates or by reverse transcription polymerase chain reaction. Time-series were developed to compare preimmunization 2001-2011 and post-immunization 2012-2013 periods. RESULTS Out of a total of 11,306 children under 5 years old with acute lower respiratory tract infections, 4974 with RCCP were included. Annual average number of hospitalizations for RCCP: 394.8 pre-immunization, 315.5 post-immunization (reduction of 20.1%, 95% confidence interval |-CI-|: 13.13-26.49%, p < 0.001). Annual average number of hospitalizations for non-viral RCCP: 255.5 pre-immunization, 183 post-immunization (reduction of 28.4%, 95% CI: 20.5-35.78%, p < 0.001). Annual average number of hospitalizations for viral RCCP: 139.2 pre-immunization, 132 post-immunization (reduction of 4.8%, 95% CI: 8.38-16.49%, p= 0.4758). The proportion of RCCP with positive viral diagnosis was 35.3 % pre-immunization and 42% post-immunization (p= 0.001). CONCLUSIONS An overall significant reduction in the number of hospitalizations for RCCP was observed following the introduction of the 13-valent pneumococcal conjugate vaccine, especially in the case of non-viral pneumonias. It is critical to continue with the epidemiological surveillance to evaluate the impact of this intervention and viral behavior in relation to RCCP.

Influenza virus: 16 years’ experience of clinical epidemiologic patterns and associated infection factors in hospitalized children in Argentina

Background Influenza is an important cause of acute lower respiratory tract infection (aLRTI), hospitalization, and mortality in children. This study aimed to describe the clinical and epidemiologic patterns and infection factors associated with influenza, and compare case features of influenza A and B. Methods In a prospective, cross-sectional study, patients admitted for aLRTI, between 2000 and 2015, were tested for respiratory syncytial virus, adenovirus, influenza, or parainfluenza, and confirmed by fluorescent antibody (FA) or real-time polymerase chain reaction (RT-PCR) assay of nasopharyngeal aspirates. Results Of 14,044 patients, 37.7% (5290) had FA- or RT-PCR-confirmed samples that identified influenza in 2.8% (394/14,044; 91.4% [360] influenza A, 8.6% [34] influenza B) of cases. Influenza frequency followed a seasonal epidemic pattern (May–July, the lowest average temperature months). The median age of cases was 12 months (interquartile range: 6–21 months); 56.1% (221/394) of cases were male. Consolidated pneumonia was the most frequent clinical presentation (56.9%; 224/394). Roughly half (49.7%; 196/394) of all cases had previous respiratory admissions; 9.4% (37/394) were re-admissions; 61.5% (241/392) had comorbidities; 26.2% (102/389) had complications; 7.8% (30/384) had nosocomial infections. The average case fatality rate was 2.1% (8/389). Chronic neurologic disease was significantly higher in influenza B cases compared to influenza A cases (p = 0.030). The independent predictors for influenza were: age ≥6 months, odds ratio (OR): 1.88 (95% confidence interval [CI]: 1.44–2.45); p<0.001; presence of chronic neurologic disease, OR: 1.48 (95% CI: 1.01–2.17); p = 0.041; previous respiratory admissions, OR: 1.71 (95% CI: 1.36–2.14); p<0.001; re-admissions, OR: 1.71 (95% CI: 1.17–2.51); p = 0.006; clinical pneumonia, OR: 1.50 (95% CI: 1.21–1.87); p<0.001; immunodeficiency, OR: 1.87 (95% CI: 1.15–3.05); p = 0.011; cystic fibrosis, OR: 4.42 (95% CI: 1.29–15.14); p = 0.018. Conclusion Influenza showed an epidemic seasonal pattern (May–July), with higher risk in children ≥6 months, or with pneumonia, previous respiratory admissions, or certain comorbidities.

Respiratory Syncytial Virus. Clinical Epidemiological Pattern and lethality associated factors in Children Admitted in a Pediatric Hospital: 15 years’ experience

Background: Respiratory Syncytial Virus (RSV) is the main agent that causes Acute Lower Respiratory Tract Infection (ALRI) in children. Objective: to describe the clinical and epidemiological pattern and the lethality factors associated to RSV infection. Methods: Prospective, cross sectional study of patients admitted for ALRI at “R.Gutierrez” Children Hospital, 2000-2014. Virological diagnosis of respiratory virus: RSV, adenovirus (AV), influenza (IF) and parainfluenza (PIV) was made by fluorescent antibody assay of nasopharyngeal aspirates or real time-PCR (IF). Results: from a total of 13.309 patients included, 38.6%(5118) had positive samples; RSV was predominant all through the study period 81% (4146/5118) without significant annual variations (71-88). It shows a seasonal epidemic pattern (median of epidemiological weeks of viral activity onset and offset:1935) and agrees with the lowest average temperature months. RSV was followed by IF: 7.4%, PIF:6% and AV:4.5%. From 5118 RSV cases the median of age was 7 months (0-216 months), 74%<1 year, 43%<6 months, 20%<3 months; 56.5% males; most frequent clinical feature was bronchiolitis 60.6%; 27% recorded previous admissions for respiratory causes. Comorbidity was found in 41.5% (1717/4146) being the most frequents: recurrent obstructive bronchitis (74%) and congenital heart disease (14%). Complications were detected in 25% of cases, 6.5% had nosocomial infections. Lethality was 1.9 %(78/4108). From 78 RSV fatal cases the median of age of was 5 months (0-180 months), 27%<3months; most frequent clinical feature was pneumonia 53%. Comorbidity was found in 65.4% (51/78) being the most frequents: recurrent obstructive bronchitis 50.9% (26/51) and congenital heart disease 33%(17/51).Moderate to severe malnourishment OR 2.28 (1.19-4.36) p<0.01, congenital cardiopathy 3.53 (1.95-6.39) p<0.01 and the presence of chronic neurological disease OR 3.25 (1.65-6.39) p<0.01 were the independent predictors for VSR lethality. Conclusion: RSV showed an epidemic pattern (May-July) and affected mostly young children. RSV lethality was more associated with malnourishment, congenital cardiopathy and the presence of chronic neurological disease. BACKGROUND AND AIMS • In Argentina, respiratory infections are the third cause of death in children under five years old. • Respiratory Syncytial Virus (RSV) is the main agent that causes Acute Lower Respiratory Tract Infection (ALRI) in children. • The aim of this study was to describe the clinical and epidemiological pattern and the lethality factors associated to RSV infection. MATERIAL AND METHODS • Study design: Prospective, cross sectional study including patients admitted for ALRI at “R.Gutierrez” Children Hospital, 2000-2014. • Active epidemiological surveillance with a specific case report form. • Inclusion criteria: all patients admitted for ALRI. • Virological diagnosis of respiratory viruses: RSV, adenovirus (AV), influenza (IF) and parainfluenza (PIV) was made by fluorescent antibody assay of nasopharyngeal aspirates or real time-PCR (IF). • Genotypes: G-glycoprotein gene ectodomain was amplified by RT-PCR and Sanger sequenced in an ABI3500 (Applied Biosystems). • Statistical Methods: Epiinfo 7 was used for data analysis. Risk factors were calculated using Odds Ratio (OR) as a measure of association with 95% confidence interval (CI); for multivaried analysis we used SPSS v.15.0 and a probability of less than 0.05 was considered significant. CONCLUSIONS • RSV showed an epidemic pattern (May-July) and affected mostly young children. • RSV lethality was more associated with malnourishment, congenital heart disease and the presence of chronic neurological disease. 546 angelagentile21@gmail.com Negative samples Positive samples RSV 81% (4146) Influenza 7.4% (378) 61,4% (8191) 38.6% (5118) n=13.309 PIV 6% (307) AV 4.5% (230) RESULTS • RSV was predominant all through the study period 81% (4146/5118) without significant annual variations (71-88). • It showed a seasonal epidemic pattern (median of epidemiological weeks of viral activity onset and offset:19-35) RSV Seasonal Pattern. 2000-2014 Population • RSV incidence remained high throughout the winter until spring. • The peaks were observed between epidemiological weeks (EW) 25-30 (June) except the years 2010 and 2012 that showed earlier peaks from 18 EW (May), coinciding with the lowest average temperature months every year. Annual Distribution of respiratory viruses (RSV, Adenovirus, Influenza, Parainfluenza) 2000-2014 (n=4146) n % Gender (male) 2342 56,5 Median of age= 7 months old (0-216 months) < 3 months 837 20.2 < 6 months 1774 42,9 < 12 months 3057 73,9 Prematurity 569 13,7 Neonatal respiratory pathology 472 11,4 Immunosuppressed 79 1,9 Malnourished 205 5 Previous admissions for respiratory causes 1101 26,6 Comorbidities (41,5%) n= 1717 Recurrent obstructive bronchitis 1270 74 Congenital heart disease 258 15 Chronic neurological disease 174 10,1 Complications (24%) n=981 Media acute otitis 307 31.3 Respiratory distress 323 32,9 Atelectasis 177 18 Sepsis 146 14,8 RSV cases Population Features RSV fatal cases Population Features (n=78) n % Gender (male) 39 50 Median of age= 5 months (1-180 months) < 3 months 27 34,6 < 6 months 40 51,3 < 12 months 60 76,9 Prematurity 19 24,4 Neonatal respiratory pathology 20 25,6 Immunosuppressed 2 2,6 Malnourished 16 20,5 Previous admissions for respiratory causes 34 43,6 Comorbidities (65,4%) n= 51 Recurrent obstructive bronchitis 26 50,9 Congenital heart disease 17 33,3 Chronic neurological disease 10 19,6 Complications (94,9%) n=74 Respiratory distress 64 82,1 Sepsis 26 33.3 Atelectasis 11 14,1 The most frequent clinical presentation was bronchiolitis (60.6%) Nosocomial infections rate: 6.5% (258/3986) Lethality rate 1.9% (78/4108). The most frequent clinical presentation was Pneumonia (53%) Nosocomial infections rate: 48,1% (37/77) 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 200