Effect of Biochar Dosage and Fineness on the Mechanical Properties and Durability of Concrete.

Biochar (BC), a byproduct of agricultural waste pyrolysis, shows potential as a sustainable substitute material for ordinary silicate cement (OPC) in concrete production, providing opportunities for environmental sustainability and resource conservation in the construction industry. However, the optimal biochar dosage and fineness for enhancing concrete performance are still unclear. This study investigated the impact of these two factors on the mechanical and durability properties of biochar concrete. Compressive and flexural strength, carbonation resistance, and chloride ion penetration resistance were evaluated by varying biochar dosages (0%, 1%, 3%, 5%, 10%) and fineness dimensions (44.70, 73.28, 750, 1020 µm), with the 0% dosage serving as the control group (CK). The results showed that the addition of 1-3 wt% of biochar could effectively reduce the rapid carbonation depth and chloride diffusion coefficient of concrete. The compressive and flexural strength of BC concrete initially increased and then decreased with the increase in biocarbon content, BC with a fineness of 73.28 µm having the most significant effect on the mechanical strength of concrete. At the dosage of 3 wt%, BC was found to promote the hydration degree of cement, improving the formation of cement hydration products. These findings provide valuable insights for the development of sustainable and high-performance cement-based materials with the appropriate use of biochar as an additive.

Correction: Effects of Chronologic Age and Young Child Exposure on Respiratory Syncytial Virus Disease among US Preterm Infants Born at 32 to 35 Weeks Gestation.

[This corrects the article DOI: 10.1371/journal.pone.0166226.].

Effects of Chronologic Age and Young Child Exposure on Respiratory Syncytial Virus Disease among US Preterm Infants Born at 32 to 35 Weeks Gestation.

OBJECTIVE: To estimate the incidence of respiratory syncytial virus (RSV) disease as a function of chronologic age and exposure to young children in US preterm infants. METHODS: In the RSV Respiratory Events among Preterm Infants Outcomes and Risk Tracking (REPORT) study, preterm infants born at 32-35 weeks gestational age (wGA) were enrolled from 188 US clinics and followed September-May of 2009-2010 or 2010-2011. Infants with medically-attended acute respiratory illness had nasal/pharyngeal swabs collected for viral testing. Results of RSV tests conducted during routine clinical care were also collected. Event rates during November-March were modeled as a function of chronologic age and birth month using Poisson regression and adjusting for other covariates. Rates were calculated overall and for infants with and without exposure to young siblings or daycare attendance. Of 3317 infants screened, 1646 were enrolled as a consecutive sample. Infants with chronic lung disease of prematurity, hemodynamically significant congenital heart disease, life expectancy <6 months, or receiving or being considered for RSV immunoprophylaxis were excluded. 84% of patients completed the study. Demographics of the enrolled cohort were generally similar to those of US infants born at 32-35 wGA; infants 32-34 wGA, Hispanic infants, and infants of less-educated mothers were under-represented. RESULTS: Among 1642 evaluable infants, outpatient RSV lower respiratory illness incidence was highest at older ages, whereas RSV hospitalization and intensive care unit (ICU) admission were highest at younger ages. In all instances, young child exposure was associated with higher RSV incidence. The highest RSV hospitalization and ICU rates occurred among February-born infants with young child exposure, at 19.0 (95% CI, 13.5-27.0) and 6.5 (95% CI, 5.6-7.6) per 100 infant-seasons, respectively. CONCLUSIONS: Preterm infants have a substantially elevated risk of RSV disease. Young age and exposure to other young children identify those at greatest risk of severe RSV disease. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00983606.

Insurance Status and the Risk of Severe Respiratory Syncytial Virus Disease in United States Preterm Infants Born at 32-35 Weeks Gestational Age.

Background. Database studies have identified that public health insurance status is associated with an increased risk of severe respiratory syncytial virus (RSV) disease in US infants. However, these studies did not adjust for the presence of other risk factors and did not evaluate the risk in preterm infants. Methods. In this study, we evaluate the independent association between public insurance and severe RSV disease outcomes adjusting for other risk factors. The prospective, observational RSV Respiratory Events among Preterm Infants Outcomes and Risk Tracking (REPORT) study was conducted over 2 consecutive RSV seasons at 188 US clinical sites that enrolled preterm infants born at 32-35 wGA who had not received RSV immunoprophylaxis with palivizumab. Adjusted incidence rates per 100 infant-seasons of the RSV-associated endpoints of outpatient lower respiratory tract infection (LRI), emergency department (ED) visits, RSV hospitalizations (RSVHs), and intensive care unit admissions during peak RSV season (November-March) were compared for infants with private and public insurance. Results. Of 1642 evaluable infants enrolled in the REPORT study, 50.1% had private insurance and 49.9% had public health insurance. Adjusted rates of RSV outpatient LRIs were similar; however, rates of ED visits (hazard ratio [HR], 2.04; 95% confidence interval [CI], 1.20-3.45) were higher for subjects with public insurance, with a similar but nonsignificant trend observed for hospitalization (HR, 1.61; 95% CI, .93-2.78). Conclusions. Socioeconomic status, as evaluated by public versus private healthcare insurance, is a significant independent risk factor for ED use in US preterm infants and may contribute to increased RSVHs in this population.

Serum palivizumab level is associated with decreased severity of respiratory syncytial virus disease in high-risk infants.

Monthly doses of palivizumab, an RSV-specific monoclonal antibody, reduce RSV-related hospitalizations (RSVH) in high-risk children; however, no specific palivizumab level has been correlated with disease severity in humans. A post hoc analysis of a previous randomized, placebo-controlled trial evaluated the relationship between serum palivizumab level at the time of RSVH and disease severity. Pediatric intensive care unit (PICU) admission was the primary severity marker. Relationships were evaluated between disease severity and gestational age, age at enrollment, age at RSVH, presence of bronchopulmonary dysplasia, sex, race, multiple birth, household smoking, daycare attendance, sibling(s), family history of atopy, duration between most recent palivizumab dose and RSVH, and palivizumab level at RSVH. Forty-two (87.5%) of 48 palivizumab recipients with RSVH had palivizumab levels drawn; 11 were admitted to the PICU. Mean palivizumab levels were lower in PICU-admitted subjects (47.2 µg/mL) vs. non-PICU subjects (98.7 µg/mL; P < 0.0001); there were no statistically significant differences in other variables examined. The probability of PICU admission declined with higher palivizumab levels; there were no PICU admissions with levels ≥ 92 µg/mL. In multivariate analyses, palivizumab level was the only independent predictor of PICU admission (P = 0.009). Palivizumab level also correlated with duration of RSVH and PICU stay, supplemental oxygen use and duration, and mechanical ventilation use and duration (P < 0.05). Higher palivizumab level was associated with decreased disease severity in high-risk infants with RSVH. Findings suggest that palivizumab level has clinical relevance, and adherence to timely monthly dosing may confer additional protection among high-risk children receiving palivizumab.

Efficacy of live attenuated influenza vaccine against influenza illness in children as a function of illness severity.

A recent study of inactivated influenza vaccine (IIV) in children aged 3-8 years demonstrated higher efficacy against moderate/severe influenza. A meta-analysis of all previous published randomized clinical trials of live attenuated influenza vaccine (LAIV) that collected information on illness severity in children aged 24-71 months was conducted. Moderate/severe influenza was defined as fever >39°C, acute otitis media, or lower respiratory tract illness; other cases were classified as milder influenza. LAIV efficacy versus placebo was 95.4% [95% confidence interval: 88.5, 98.1] (year 1) and 88.5% [77.4, 94.9] (year 2) against moderate/severe influenza and 91.4% [77.9, 96.7] (year 1) and 84.2% [56.7, 94.3] (year 2) against milder influenza. The relative efficacy of LAIV versus IIV was 52.2% [31.6, 66.6] for moderate/severe influenza and 45.0% [28.6, 57.5] for milder influenza. Efficacy against all influenza illnesses, regardless of severity, is critical to prevent influenza illness and transmission in the community.

Respiratory syncytial virus disease in preterm infants in the U.S. born at 32-35 weeks gestation not receiving immunoprophylaxis.

BACKGROUND: The Respiratory Syncytial Virus (RSV) Respiratory Events Among Preterm Infants Outcomes and Risk Tracking (REPORT) study evaluated RSV disease burden in U.S. preterm infants 32-35 weeks gestational age (wGA) not receiving RSV prophylaxis. METHODS: Preterm infants <6 months of age as of November 1st were followed prospectively at 188 clinics from September to May 2009-2010 or 2010-2011. Nasal and pharyngeal swabs were collected for medically attended acute respiratory illnesses (MAARI) and tested for RSV by qRT-polymerase chain reaction. Risk factors were assessed using multivariate Cox proportional hazard model adjusted for seasonality. RESULTS: Of 1642 evaluable infants, 287 experienced RSV MAARI. Rates of RSV-related MAARI, outpatient lower respiratory tract illness, emergency department visits and hospitalization (RSVH) during November to March were 25.4, 13.7, 5.9 and 4.9 per 100 infant-seasons, respectively. Preschool-aged, nonmultiple-birth siblings and daycare attendance were consistently associated with increased risk of RSV. RSVH rates were highest in infants 32-34 and 35 wGA who were <6 months of age during November to March with daycare attendance or nonmultiple-birth, preschool-aged siblings (8.9 and 9.3 per 100 infant-seasons, respectively, versus 3.5 for all other infants, P<0.001). Chronologic age <3 months was associated with a higher RSVH rate for infants 35 wGA but not for infants 32-34 wGA. CONCLUSIONS: In US preterm infants who were 32-35 wGA, <6 months on November 1st and not receiving RSV prophylaxis, the burden of RSV MAARI was 25 per 100 infant-seasons. The highest RSVH rates occurred among those with daycare attendance or nonmultiple-birth, preschool-aged siblings while they were <6 months of age during the RSV season.

A postlicensure evaluation of the safety of Ann Arbor strain live attenuated influenza vaccine in children 24-59 months of age.

BACKGROUND: In the United States, live attenuated influenza vaccine (LAIV) was initially approved for use in individuals aged 5-49 years in 2003, which was extended to individuals aged 2-49 years in 2007. At that time, a postlicensure commitment was made to describe the safety of LAIV within a cohort of eligible children aged 2-5 years. METHODS: A prospective observational postmarketing study was conducted to evaluate the safety of LAIV. Rates of medically attended events (MAEs) and serious adverse events (SAEs) in eligible children aged 24-59 months receiving LAIV as part of routine care from October 2007 to March 2010 were compared with rates in a within-cohort self-control, as well as matched unvaccinated and matched trivalent inactivated influenza vaccine (TIV)-vaccinated controls. Children with asthma and other high-risk medical conditions before vaccination were excluded. All MAEs and SAEs through 42 days postvaccination and all hospitalizations and deaths through 6 months postvaccination were analyzed. Statistical significance was declared without multiplicity adjustment. RESULTS: A total of 28,226 unique LAIV recipients were matched with similar numbers of TIV-vaccinated and unvaccinated children. Of 4696 MAE incidence rate comparisons, 83 (1.8%) were statistically significantly higher and 221 (4.7%) were statistically significantly lower in LAIV recipients versus controls. No pattern of MAE rate differences suggested a safety signal with LAIV. Asthma/wheezing MAEs were not statistically increased in LAIV recipients. No anaphylaxis events occurred within 3 days postvaccination. Rates of SAEs were similar between LAIV and control groups. CONCLUSIONS: Results of this postlicensure evaluation of LAIV safety in US children are consistent with preapproval clinical studies and Vaccine Adverse Event Reporting System reports, both of which demonstrated no significant increase in asthma/wheezing events or other adverse outcomes among eligible children aged 24-59 months who received LAIV.

Distribution of respiratory syncytial virus subtypes A and B among infants presenting to the emergency department with lower respiratory tract infection or apnea.

BACKGROUND: Respiratory syncytial virus (RSV), a leading viral respiratory pathogen worldwide, has 2 major subtypes, A and B. OBJECTIVE: To describe the temporal and geographic distribution and parameters of disease severity associated with RSV A and B in the United States. METHODS: A US multicenter active surveillance study was conducted in emergency departments (EDs) during 2 RSV seasons. Infants <1 year of age presenting to the ED with symptoms of lower respiratory tract infection or apnea were enrolled. RSV subtypes were detected in nasal swabs by reverse transcriptase polymerase chain reaction. RESULTS: Of 4248 patients enrolled, 4172 patients were evaluable; 32.4% of patients were positive for any RSV subtype in season 1 and 29.9% in season 2. RSV A and B were detected in each region studied. More patients presented to the ED with RSV A than with RSV B (853 [20.4%] versus 453 [10.9%], respectively); RSV A-positive patients were more likely to be admitted to the hospital or intensive care unit (47.7%, versus RSV B, 35.8%; P < 0.0001); hospitalized RSV A-positive patients were less likely to be prescribed antibiotics (32.4%, versus RSV B, 47.8%; P < 0.001). CONCLUSIONS: This is the largest epidemiologic study in EDs reporting trends in RSV subtypes. RSV subtypes A and B were documented in both seasons across all US regions studied and detected in September to May. The results of this study support suggestions from smaller studies that RSV A may be more virulent than RSV B; however, more quantitative assessments of disease severity are needed.

Effectiveness of intranasal live attenuated influenza vaccine against all-cause acute otitis media in children.

BACKGROUND: Acute otitis media (AOM) is a frequent complication of influenza in children, and influenza vaccination helps protect against influenza-associated AOM. A live attenuated influenza vaccine (LAIV) approved for eligible children aged ≥2 years for the prevention of influenza also effectively reduces influenza-associated AOM. However, the annual effectiveness of LAIV against all-cause AOM is unknown. METHODS: AOM rates in children aged 6-83 months from 6 randomized, placebo-controlled trials and 2 randomized, inactivated influenza vaccine-controlled trials were pooled and analyzed. To enable comparison with studies of AOM prevention by pneumococcal conjugate vaccines, 12-month effectiveness was calculated assuming that LAIV had no effect outside of influenza seasons. RESULTS: During influenza seasons, LAIV efficacy compared with placebo against all-cause AOM in children aged 6-71 months (N = 9497) was 12.4% (95% confidence interval [CI]: 2.0%, 21.6%) in year 1. In year 2, the efficacy in children aged 18-83 months (N = 4142) was 6.2% (95% CI: -12.4%, 21.7%). Compared with inactivated influenza vaccine, the efficacy of LAIV in children aged 6-71 months (N = 9901) against febrile all-cause AOM was 9.7% (95% CI: -2.1%, 20.1%). The estimated 12-month effectiveness of LAIV compared with placebo against all-cause AOM was 7.5% (95% CI: -2.4%, 16.2%). CONCLUSIONS: LAIV reduced the incidence of all-cause AOM compared with placebo in children. The estimated 12-month effectiveness of LAIV was comparable with 7-valent pneumococcal conjugate vaccine. The effects of the vaccines will overlap somewhat; however, because pneumococcal conjugate vaccines only prevent a fraction of all pneumococcal AOM and influenza-associated AOM can be caused by other pathogens, LAIV could further reduce the incidence of AOM in children.

The safety and effectiveness of self-administration of intranasal live attenuated influenza vaccine in adults.

Intranasal live attenuated influenza vaccine (LAIV) has potential for self-administration (SA) by adults and adolescents, which could save time and cost in mass vaccination settings. Participants in a study of LAIV in adults (n=4561) selected either SA or health care provider (HCP) administration and were followed for febrile illness during the influenza season. More LAIV recipients chose SA-LAIV (72%) than HCP-LAIV (28%). Overall, 97% of SA-LAIV and 98% of HCP-LAIV recipients had no problems with vaccine administration. Four of 13 study sites enrolled more than 50 subjects in both cohorts. Overall and for these 4 sites, illness incidence was similar with SA-LAIV and HCP-LAIV. Solicited reactogenicity events and adverse events through 7 days post vaccination were comparable for SA-LAIV and HCP-LAIV recipients; both groups exhibited increased runny nose, sore throat, and cough relative to placebo recipients. SA-LAIV and HCP-LAIV appeared similarly effective against influenza-like illness and had comparable safety profiles.

The role of nasal IgA in children vaccinated with live attenuated influenza vaccine.

BACKGROUND: Immunoglobulin A (IgA) is the predominant antibody produced in response to mucosal infections. The role of IgA in providing protection against influenza in children vaccinated with live attenuated influenza vaccine (LAIV) has not been well described. METHODS: Nasal IgA responses were assessed using data from 3 prospective, 2-year, randomized studies comparing LAIV with placebo in children 6-36 months of age. In each study, samples were collected in a subset of patients; a new cohort was enrolled each year. Ratios of strain-specific nasal IgA to total nasal IgA were calculated and prevaccination to postvaccination geometric mean fold-rises (GMFRs) were evaluated. Mean postvaccination IgA ratios were compared for subjects with and without confirmed influenza illness by study and in pooled analyses. RESULTS: Across studies, a higher percentage of children receiving LAIV had a ≥ 2-fold increase in strain-specific IgA ratio compared with placebo recipients. GMFRs after LAIV in years 1 and 2 ranged from 1.2 to 6.2, compared with 0.5-2.2 among placebo recipients. Similar responses were observed in subjects who were baseline seronegative and seropositive based on serum hemagglutination inhibition antibody titers. In years 1 and 2, the mean postvaccination strain-specific to total IgA ratio was 3.1-fold (P<0.01) and 2.0-fold (P<0.03) higher among LAIV recipients with no evidence of culture-confirmed influenza illness compared with LAIV recipients who developed culture-confirmed influenza illness; a similar and consistent trend was observed for each individual study and type/subtype. CONCLUSIONS: The current analysis demonstrates that nasal IgA contributes to the efficacy of LAIV and can provide evidence of vaccine-induced immunity. However, the inherent heterogeneity in nasal antibody levels and variability in nasal specimen collection hinders the precise evaluation of mucosal antibody responses. Other studies have demonstrated that LAIV-induced immunity is also partially explained by T-cell immunity, serum antibody responses, and innate immunity, consistent with the multi-faceted nature of immunity induced by wild-type influenza infection and other live virus vaccines.

A postmarketing evaluation of the safety of Ann Arbor strain live attenuated influenza vaccine in adults 18-49 years of age.

BACKGROUND: The Ann Arbor strain-live attenuated influenza vaccine (LAIV) was licensed in 2003 for use in the United States for individuals aged 5-49 years of age. As part of a postmarketing commitment to safety, LAIV was studied in adults 18-49 years participating in the Kaiser Permanente Health Plan over 5 influenza seasons. METHODS: Individuals received LAIV as part of routine care from October 2003 through March 2008. Using Kaiser Permanente databases, rates of medically attended events (MAEs) and serious adverse events (SAEs) in LAIV recipients were compared with rates in multiple non-randomized control groups which included a self-control group, matched unvaccinated controls, and matched controls vaccinated with inactivated influenza vaccine (TIV). RESULTS: A total of 21,340, 18,316, and 21,340 subjects received LAIV, TIV and no vaccine, respectively. More than 5500 MAE incidence rate comparisons were performed, and of these, 257 (5%) yielded statistically significant differences with 72 and 185 occurring at a higher and lower rate after LAIV compared with control groups, respectively. The pattern of MAE rate differences did not suggest any safety signal associated with LAIV. There were 47 SAEs noted, and no individual SAE occurred at a significantly higher or lower rate in LAIV recipients relative to control groups in any comparison. Only 2 SAEs (migraine/sinusitis and Bell's palsy) were considered possibly or probably related to LAIV. CONCLUSION: The results of this post-licensure evaluation of LAIV safety in individuals 18-49 years of age are consistent with pre- and post-approval clinical studies as well as reports to the U.S. Vaccine Adverse Events Reporting System, all of which demonstrated no significant adverse outcomes among eligible individuals following receipt of LAIV.

A postmarketing evaluation of the safety of Ann Arbor strain live attenuated influenza vaccine in children 5 through 17 years of age.

BACKGROUND: Live attenuated influenza vaccine (LAIV) was licensed in 2003 in the United States for use in individuals aged 5-49 years. METHODS: A prospective observational postmarketing study was conducted to evaluate the safety of LAIV. Rates of medically attended events (MAEs) and serious adverse events (SAEs) in eligible children aged 5-17 years receiving LAIV as part of routine care from October 2003 to March 2008 were compared with rates in nonrandomized self, matched unvaccinated, and matched trivalent inactivated influenza vaccine (TIV)-vaccinated controls. All MAEs and SAEs through 42 days postvaccination and all hospitalizations and deaths through 6 months postvaccination were analyzed. Statistical significance was assigned without multiplicity adjustment. RESULTS: 43,702 LAIV recipients were matched with similar numbers of TIV-vaccinated and unvaccinated children. Of approximately 9500 MAE incidence rate comparisons, 204 were statistically significantly higher and 168 were statistically significantly lower in LAIV recipients versus controls. No pattern of MAE rate differences suggested a safety signal with LAIV. Asthma/wheezing MAEs were not statistically increased in LAIV recipients. No anaphylaxis events occurred within 3 days postvaccination. Rates of SAEs were similar between LAIV and control groups. Two SAEs were considered possibly related to LAIV: Bell's palsy and nonspecific paroxysmal spell. CONCLUSIONS: Results of this postlicensure evaluation of LAIV safety in US children aged 5-17 years are consistent with preapproval clinical studies and Vaccine Adverse Event Reporting System reports, both of which demonstrated no significant increase in asthma/wheezing events or other adverse outcomes among eligible children who received LAIV.

The efficacy of intranasal live attenuated influenza vaccine in children 2 through 17 years of age: a meta-analysis of 8 randomized controlled studies.

BACKGROUND: Nine randomized controlled clinical trials, including approximately 26,000 children aged 6 months to 17 years, have evaluated the efficacy of live attenuated influenza vaccine (LAIV) against culture-confirmed influenza illness compared with placebo or trivalent inactivated influenza vaccine (TIV). The objective of the current analysis was to integrate available LAIV efficacy data in children aged 2-17 years, the group for whom LAIV is approved for use. METHODS: A meta-analysis was conducted using all available randomized controlled trials and a fixed-effects model. Cases caused by drifted influenza B were analyzed as originally classified and with all antigenic variants classified as dissimilar. RESULTS: Five placebo-controlled trials (4 were 2-season trials) and 3 single-season TIV-controlled trials were analyzed. Compared with placebo, year 1 efficacy of 2 doses of LAIV was 83% (95% CI: 78, 87) against antigenically similar strains; efficacy was 87% (95% CI: 78, 93), 86% (95% CI: 79, 91), and 76% (95% CI: 63, 84) for A/H1N1, A/H3N2, and B, respectively. Classifying B variants as dissimilar, efficacy against all similar strains was 87% (95% CI: 83, 91) and 93% (95% CI: 83, 97) against similar B strains. Year 2 efficacy was 87% (95% CI: 82, 91) against similar strains. Compared with TIV, LAIV recipients experienced 44% (95% CI: 28, 56) and 48% (95% CI: 38, 57) fewer cases of influenza illness caused by similar strains and all strains, respectively. LAIV efficacy estimates for children from Europe, the United States, and Middle East were robust and were similar to or higher than those for the overall population. CONCLUSIONS: In children aged 2-17 years, LAIV demonstrated high efficacy after 2 doses in year 1 and revaccination in year 2, and greater efficacy compared with TIV. This meta-analysis provides precise estimates of LAIV efficacy among the approved pediatric age group.

Evidence of homosubtypic but not heterosubtypic immunity in young children following wild-type influenza illness.

The effect of subtype-specific influenza illness in young children on the probability of influenza illness in the following year was analyzed for placebo recipients in four 2-year vaccine efficacy studies. There was evidence of homosubtypic protection but no evidence of heterosubtypic protection; however, a moderate-to-low level of heterosubtypic protection could not be ruled out. This analysis supports previous observations that children do not develop lasting, clinically significant heterosubtypic protection after influenza illness.

The efficacy of live attenuated and inactivated influenza vaccines in children as a function of time postvaccination.

BACKGROUND: In the United States, more children are being vaccinated against influenza in August and September, months before peak influenza activity. Sustained vaccine efficacy through 12 months postvaccination has been demonstrated in children for live attenuated influenza vaccine (LAIV) but not trivalent inactivated influenza vaccine (TIV). Three large, randomized studies compared LAIV and TIV efficacy in children, providing the opportunity to examine the impact of time on the relative efficacy of the 2 vaccines. METHODS: For each study, the relative efficacy of LAIV versus TIV was analyzed by time interval (0-4 and >4-8 months postvaccination) for matched and mismatched strains. RESULTS: LAIV recipients had less influenza than TIV recipients during both intervals; the relative efficacy of LAIV versus TIV for matched strains in each study increased from 0 to 4 months (range, 25%-60%) to >4 to 8 months (range, 49%-89%). Analysis of the incidence of individual types/subtypes revealed the same pattern for the predominant matched strain in each study; no consistent pattern was seen for lower-incidence matched strains. For mismatched strains, similar relative efficacy was seen in each time interval. CONCLUSIONS: For matched strains, data suggest that the relative efficacy of LAIV versus TIV in young children increases over time. Consistent with previous studies of TIV-induced immunity, this analysis suggests that the absolute efficacy of TIV against matched strains in children may be lower at >4 to 8 versus 0 to 4 months postvaccination. Relative efficacy against mismatched strains was similar over time, consistent with previous estimates of the absolute efficacies of the vaccines against mismatched strains. Further research is needed to confirm these findings and to characterize the duration of protection provided by TIV in children.