Komal J. Narwaney

Parental Decline of Pneumococcal Vaccination and Risk of Pneumococcal Related Disease in Children

BACKGROUND An increasing number of parents are choosing to decline immunizations for their children. This study examined the association between the parental decision to decline pneumococcal conjugate (PCV7) vaccinations and the risk of hospitalization due to pneumococcal disease or lobar pneumonia in children. METHODS We conducted a case-control study nested within a cohort of children enrolled in the Kaiser Permanente Colorado (KPCO) health plan between 2004 and 2009. Each child hospitalized with pneumococcal disease or lobar pneumonia (n=106) was matched to 4 randomly selected controls (n=401). Cases were matched to controls by age, sex, high-risk status, calendar time, and length of enrollment in KPCO. Disease status and parental vaccination decisions were validated with medical record review. Cases and controls were classified as vaccine decliners or vaccine acceptors. RESULTS Among 106 cases, there were 6 (6%) PCV7 vaccine decliners; among 401 controls, there were 4 (1%) vaccine decliners. Children of parents who declined PCV7 immunization were 6.5 times (OR=6.5; 95% CI=1.7, 24.5) more likely to be hospitalized for invasive pneumococcal disease or lobar pneumonia than vaccinated children. CONCLUSIONS Parental decline of pneumococcal vaccination apparently increases the risk for hospitalization due to pneumococcal disease or lobar pneumonia in children. Providers can use this information when helping parents weigh the benefits and risks of immunizing their children.

Association Between Undervaccination With Diphtheria, Tetanus Toxoids, and Acellular Pertussis (DTaP) Vaccine and Risk of Pertussis Infection in Children 3 to 36 Months of Age

IMPORTANCE Undervaccination is an increasing trend that potentially places children and their communities at an increased risk for serious infectious diseases. OBJECTIVE To examine the association between undervaccination and pertussis in children 3 to 36 months of age. DESIGN Matched case-control study with conditional logistic regression analysis. SETTING Eight managed care organizations of the Vaccine Safety Datalink between 2004 and 2010. PARTICIPANTS Each laboratory-confirmed case of pertussis (72 patients) was matched to 4 randomly selected controls (for a total of 288 controls). The case patients were matched to controls by managed care organization site, sex, and age at the index date. The index date was defined as the date of pertussis diagnosis for the case patients. EXPOSURE Undervaccination for the diphtheria, tetanus toxoids, and acellular pertussis (DTaP) vaccine. Undervaccination was defined as the number of doses of DTaP vaccine that was either missing or delayed by the index date. Case patients and controls could be undervaccinated by 0, 1, 2, 3, or 4 doses of DTaP vaccine. Children undervaccinated by 0 doses were considered age-appropriately vaccinated by the index date. MAIN OUTCOME AND MEASURE Pertussis. RESULTS Of the 72 case patients with pertussis, 12 (16.67%) were hospitalized, and 34 (47.22%) were undervaccinated for DTaP vaccine by the date of pertussis diagnosis. Of the 288 matched controls, 64 (22.22%) were undervaccinated for DTaP vaccine. Undervaccination was strongly associated with pertussis. Children undervaccinated for 3 or 4 doses of DTaP vaccine were 18.56 (95% CI, 4.92-69.95) and 28.38 (95% CI, 3.19-252.63) times more likely, respectively, to have received a diagnosis of pertussis than children who were age-appropriately vaccinated. CONCLUSIONS AND RELEVANCE Undervaccination with DTaP vaccine increases the risk of pertussis among children 3 to 36 months of age.

Safety of Trivalent Inactivated Influenza Vaccine in Children Aged 24 to 59 Months in the Vaccine Safety Datalink

OBJECTIVES To evaluate the safety of trivalent inactivated influenza vaccine (TIV) in children aged 24 to 59 months and to evaluate the risk of medically attended events (MAEs) in a subcohort of children who had multiple annual doses of TIV over their lifetimes. DESIGN Self-controlled screening study. SETTING Seven US managed care organizations from October 1, 2002, to March 31, 2006. PARTICIPANTS Children aged 24 to 59 months who received at least 1 TIV dose (66 283 children and 91 692 TIV doses). EXPOSURE Vaccination with TIV. MAIN OUTCOME MEASURES Medically attended events in inpatient and emergency department settings in one of the following risk windows: 0 to 2, 1 to 14, or 1 to 42 days after vaccination. All MAEs that met the screening criteria of incidence rate ratios (IRRs) exceeding 1.0 and P ≤ .05 or IRRs exceeding 2.0 and P < .20 underwent medical record review. A secondary analysis examined the risk of MAEs in children who had multiple annual lifetime TIV doses. RESULTS Nine diagnoses met the screening criteria. After medical record review, gastrointestinal tract symptoms (IRR, 1.18; 95% confidence interval [CI], 1.10-1.25), gastrointestinal tract disorders (7.70; 1.11-53.52), and fever (1.71; 1.64-1.80) remained significantly associated with vaccination. None of the events seemed to be serious, and none had complications. In the secondary analysis, there was an apparent dose response for vaccine and allergic reactions in the 1- to 3-day risk window. CONCLUSIONS There was no evidence of serious MAEs following vaccination with TIV among children aged 24 to 59 months. Further studies are warranted to evaluate the risk of MAEs in children with multiple lifetime TIV doses.

Timely versus delayed early childhood vaccination and seizures

BACKGROUND: Little is known regarding the timing of childhood vaccination and postvaccination seizures. METHODS: In a cohort of 323 247 US children from the Vaccine Safety Datalink born from 2004 to 2008, we analyzed the association between the timing of childhood vaccination and the first occurrence of seizure with a self-controlled case series analysis of the first doses of individual vaccines received in the first 2 years of life. RESULTS: In infants, there was no association between the timing of infant vaccination and postvaccination seizures. In the second year of life, the incident rate ratio (IRR) for seizures after receipt of the first measles-mumps-rubella vaccine (MMR) dose at 12 to 15 months was 2.65 (95% confidence interval [CI] 1.99–3.55); the IRR after an MMR dose at 16 to 23 months was 6.53 (95% CI 3.15–13.53). The IRR for seizures after receipt of the first measles-mumps-rubella-varicella vaccine (MMRV) dose at 12 to 15 months was 4.95 (95% CI 3.68–6.66); the IRR after an MMRV dose at 16 to 23 months was 9.80 (95% CI 4.35 –22.06). CONCLUSIONS: There is no increased risk of postvaccination seizure in infants regardless of timing of vaccination. In year 2, delaying MMR vaccine past 15 months of age results in a higher risk of seizures. The strength of the association is doubled with MMRV vaccine. These findings suggest that on-time vaccination is as safe with regard to seizures as delayed vaccination in the first year of life, and that delayed vaccination in the second year of life is associated with more postvaccination seizures than on-time vaccination.

Development of an Interactive Social Media Tool for Parents With Concerns About Vaccines

Objective. Describe a process for designing, building, and evaluating a theory-driven social media intervention tool to help reduce parental concerns about vaccination. Method. We developed an interactive web-based tool using quantitative and qualitative methods (e.g., survey, focus groups, individual interviews, and usability testing). Results. Survey results suggested that social media may represent an effective intervention tool to help parents make informed decisions about vaccination for their children. Focus groups and interviews revealed four main themes for development of the tool: Parents wanted information describing both benefits and risks of vaccination, transparency of sources of information, moderation of the tool by an expert, and ethnic and racial diversity in the visual display of people. Usability testing showed that parents were satisfied with the usability of the tool but had difficulty with performing some of the informational searches. Based on focus groups, interviews, and usability evaluations, we made additional revisions to the tool’s content, design, functionality, and overall look and feel. Conclusion. Engaging parents at all stages of development is critical when designing a tool to address concerns about childhood vaccines. Although this can be both resource- and time-intensive, the redesigned tool is more likely to be accepted and used by parents. Next steps involve a formal evaluation through a randomized trial.

Safety of diphtheria, tetanus, acellular pertussis and inactivated poliovirus (DTaP–IPV) vaccine

BACKGROUND In 2008, a diphtheria, tetanus, acellular pertussis, and inactivated poliovirus combined vaccine (DTaP-IPV) was licensed for use in children 4 through 6 years of age. While pre-licensure studies did not demonstrate significant safety concerns, the number vaccinated in these studies was not sufficient to examine the risk of uncommon but serious adverse events. OBJECTIVE To assess the risk of serious adverse events following DTaP-IPV vaccination. METHODS The study was conducted from January 2009 through September 2012 in the Vaccine Safety Datalink (VSD) project. In the VSD, electronic vaccination and encounter data are updated and aggregated weekly as part of ongoing surveillance activities. Based on previous reports and biologic plausibility, eight potential adverse events were monitored: meningitis/encephalitis; seizures; stroke; Guillain-Barré syndrome; Stevens-Johnson syndrome; anaphylaxis; serious allergic reactions other than anaphylaxis; and serious local reactions. Adverse event rates in DTaP-IPV recipients were compared to historical incidence rates in the VSD population prior to 2009. Sequential probability ratio testing was used to analyze the data on a weekly basis. RESULTS During the study period, 201,116 children received DTaP-IPV vaccine. Ninety-seven percent of DTaP-IPV recipients also received other vaccines on the same day, typically measles-mumps-rubella and varicella vaccines. There was no statistically significant increased risk of any of the eight pre-specified adverse events among DTaP-IPV recipients when compared to historical incidence rates. CONCLUSIONS In this safety surveillance study of more than 200,000 DTaP-IPV vaccine recipients, there was no evidence of increased risk for any of the pre-specified adverse events monitored. Continued surveillance of DTaP-IPV vaccine safety may be warranted to monitor for rare adverse events, such as Guillain-Barré syndrome.

Trivalent Inactivated Influenza Vaccine Is Not Associated With Sickle Cell Crises in Children

Background and Objectives: Children with sickle cell disease are considered at high risk for complications from influenza infection and are recommended to receive annual influenza vaccination. However, data on the safety of influenza vaccination in children with sickle cell anemia are sparse. Methods: Using a retrospective cohort of children aged 6 months to 17 years in 8 managed care organizations that comprise the Vaccine Safety Datalink and who had a diagnosis of sickle cell anemia from 1999 to 2006, we conducted matched case-control and self-controlled case series studies to examine the association of trivalent inactivated influenza vaccination with hospitalization for sickle cell crisis in the 2 weeks after vaccination. Results: From an original pool of 1085 pediatric subjects with a diagnosis of sickle cell anemia, we identified 179 children with at least 1 sickle cell crisis during any influenza season (October 1–March 31). In the matched case-control study (matching on age category, gender, Vaccine Safety Datalink site, and season), the odds ratio of hospitalization for a crisis in vaccinated compared with unvaccinated children was not significant: 1.3 (95% confidence interval 0.8–2.2). In the self-controlled case series study of hospitalized cases, the incident rate ratio for hospitalization with sickle cell crisis in the 2 weeks after trivalent inactivated influenza vaccination was also not significant: 1.2 (95% confidence interval 0.75–1.95). Conclusions: This large cohort study did not find an association of influenza vaccination and hospitalization for sickle cell crises in children with sickle cell anemia.

Association of HLA class II genes with clinical hyporesponsiveness to trivalent inactivated influenza vaccine in children

BACKGROUND The primary prevention measure for influenza infection has been the use of influenza vaccines. However, even when the vaccine and circulating strains are well-matched, some healthy children do not respond to the vaccine, likely due to a genetic basis for immune hyporesponsiveness. The primary objective of this study was to identify HLA class II genes associated with clinical hyporesponsiveness after trivalent inactivated influenza vaccine (TIV) in children. METHODS We conducted a case-control study nested within a retrospective cohort of children that were screened at birth for HLA-DR,DQ genotypes by the Diabetes Autoimmunity Study in the Young (DAISY) and were subsequently followed for up to 8 years by Kaiser Permanente, Colorado (KPCO). Hyporesponsiveness was clinically defined as the occurrence of influenza or influenza-like illness (ILI) in peak influenza weeks in children fully vaccinated with TIV. Each child with clinical hyporesponse (n=252) was matched to 4 randomly selected controls (n=1006) by age and season. Children with clinical hyporesponse to TIV were identified using the Kaiser electronic clinical and immunization databases. Fully vaccinated children within the KPCO-DAISY cohort who did not have a diagnosis of ILI during the entire influenza season were eligible to be controls for that season. Class II HLA-DRB1 and HLA-DQB1 genes were the primary exposure variables. We used conditional logistic regression to calculate the matched odds ratios. RESULTS In non-Hispanic white children, HLA-DR7/4,DQB1 0302 genotype was significantly associated (OR=5.15; 95% CI=1.94, 13.67; p=0.001), while in Hispanic children, HLA-DRB1 15 or 16 allele (OR=0.31; 95% CI=0.14, 0.69; p=0.004) and HLA-DR7/Y (DRB1 11, DRB1 13 and DRB1 14) genotype (OR=5.84; 95% CI=1.68, 20.28; p=0.006) were significantly associated with clinical hyporesponsiveness after TIV. CONCLUSIONS HLA class II genes are associated with clinical hyporesponsiveness to TIV. This finding is important as it may help identify a group of children who are not protected by the commonly used TIV and may require alternative preventive strategies.

Risk of adverse events following oseltamivir treatment in influenza outpatients, Vaccine Safety Datalink Project, 2007–2010†

An association between the influenza antiviral medication oseltamivir and neuropsychiatric events has been suggested by post‐marketing case reports in Japan. This possible association was not supported by cohort studies in the U.S. conducted prior to the 2009 influenza A (H1N1) pandemic, when usage rates were comparatively low. We assessed oseltamivir safety before and during the pandemic using biologically plausible risk intervals, particularly focusing on psychiatric events.

Prediction Model for Two-Year Risk of Opioid Overdose Among Patients Prescribed Chronic Opioid Therapy

BackgroundNaloxone is a life-saving opioid antagonist. Chronic pain guidelines recommend that physicians co-prescribe naloxone to patients at high risk for opioid overdose. However, clinical tools to efficiently identify patients who could benefit from naloxone are lacking.ObjectiveTo develop and validate an overdose predictive model which could be used in primary care settings to assess the need for naloxone.DesignRetrospective cohort.SettingDerivation site was an integrated health system in Colorado; validation site was a safety-net health system in Colorado.ParticipantsWe developed a predictive model in a cohort of 42,828 patients taking chronic opioid therapy and externally validated the model in 10,708 patients.Main MeasuresPotential predictors and outcomes (nonfatal pharmaceutical and heroin overdoses) were extracted from electronic health records. Fatal overdose outcomes were identified from state vital records. To match the approximate shelf-life of naloxone, we used Cox proportional hazards regression to model the 2-year risk of overdose. Calibration and discrimination were assessed.Key ResultsA five-variable predictive model showed good calibration and discrimination (bootstrap-corrected c-statistic = 0.73, 95% confidence interval [CI] 0.69–0.78) in the derivation site, with sensitivity of 66.1% and specificity of 66.6%. In the validation site, the model showed good discrimination (c-statistic = 0.75, 95% CI 0.70–0.80) and less than ideal calibration, with sensitivity and specificity of 82.2% and 49.5%, respectively.ConclusionsAmong patients on chronic opioid therapy, the predictive model identified 66–82% of all subsequent opioid overdoses. This model is an efficient screening tool to identify patients who could benefit from naloxone to prevent overdose deaths. Population differences across the two sites limited calibration in the validation site.