Manika Suryadevara

Clinical features, adenovirus types, and local production of inflammatory mediators in adenovirus infections.

Background: Adenovirus infection manifests in many ways, with respiratory and gastrointestinal symptoms predominating. Methods: We performed a retrospective chart review on children evaluated at our center who had a nasal wash culture positive for adenovirus. Archived nasal washes were retrieved. Polymerase chain reaction for 15 respiratory viruses was performed on these samples. Patients who were coinfected with another virus were excluded. Adenovirus typing was performed using polymerase chain reaction primers directed at the conserved hexon gene. Bead proteomics was used to measure concentrations of inflammatory mediators. Results: Seventy-eight patients were infected only with adenovirus. The clinical diagnosis was upper respiratory infection in 60%, pneumonia in 18%, febrile seizure in 8%, and bronchiolitis in 6%. Subgroup-C and B1 infections were most common. Seventy percent of patients with upper respiratory infection and all 5 patients with bronchiolitis had a subgroup-C infection; pneumonia was caused by subgroup-B1 and C viruses. Compared with asymptomatic control patients, adenovirus infected patients had higher nasal wash concentrations of interleukin (IL)-1α, IL-6, inducible protein-10, macrophage inflammatory protein-1α, tumor necrosis factor α, monokine induced by gamma interferon, and interferon-α (P < 0.05). In addition, we found that IL-8 and IL-1α (P < 0.05) were higher in the nasal washes obtained from hospitalized patients than in nonhospitalized patients. Conclusions: Adenovirus infection causes an array of clinical disease and is associated with local production of several proinflammatory cytokines. The observation that nasal wash IL-8 and IL-1α concentrations were higher in patients requiring hospitalization suggests that these mediators contribute to disease severity.

Novel inflammatory markers, clinical risk factors and virus type associated with severe respiratory syncytial virus infection.

Background: Virus-induced inflammation contributes to respiratory syncytial virus (RSV) pathogenesis. We sought to determine the specific mediators that are associated with more severe illness in young children. Methods: Children ⩽5 years of age seen in our emergency department for respiratory symptoms from September 1998 to May 2008 were eligible for enrollment. Nasopharyngeal wash samples were collected from all eligible patients, and clinical data were recorded. Individuals were included in this study if nasopharyngeal wash samples were positive for RSV only. Patients enrolled in the study were stratified by disease severity, defined as mild (not hospitalized), moderate (hospitalized) or severe (requiring intensive care unit stay). Concentrations of individual inflammatory biomarkers in nasopharyngeal wash fluids were determined using the Luminex human 30-plex assay. Results: Eight hundred fifty-one patients met study criteria: 268 (31.5%) with mild, 503 (59.1%) with moderate and 80 (9.4%) with severe illness. As expected, illness severity was directly associated with young age, prematurity, heart or lung disease, infection with RSV group A and elevated concentrations of interleukin (IL)-2R, IL-6, CXCL8, tumor necrosis factor-&agr;, interferon-&agr;, CCL3, CCL4 and CCL2. In addition, we report several novel and mechanistically important inflammatory biomarkers of severe RSV disease, including IL-1&bgr;, IL1-RA, IL-7, epidermal growth factor and hepatocyte growth factor. Conclusions: In a large, longitudinal study (10 years, 851 enrolled patients) limited to RSV infection only, in which well-known risk factors are confirmed, we identified 5 novel biomarkers specifically of severe disease. These markers may ultimately serve to elucidate disease mechanisms.

Viral Etiology of Acute Febrile Respiratory Illnesses in Hospitalized Children Younger Than 24 Months

Background: Respiratory infections are a leading cause of pediatric hospitalizations. This study investigated whether virus—virus or virus—Bordetella co-infections are more frequent or more severe than previously recognized. Methods: This is a 3-year prospective study of children younger than 24 months hospitalized with a febrile respiratory illness. Viral pathogens were detected using multiplex polymerase chain reaction (PCR), enzyme-linked immunoassays, and/or viral cultures from nasopharyngeal samples. Bordetella infections were detected by PCR. Results: A total of 201 patients were enrolled. Respiratory viruses were detected in 187 (93%) patients, with 52 (28%) multipathogen infections. The most common viruses detected were respiratory syncytial virus and rhinovirus/enterovirus. There were no differences in illness severity when comparing patients infected with one pathogen and those with multipathogen infection. Conclusion: Virus co-infection in young children hospitalized with an acute febrile respiratory infection is common but does not appear to be associated with illness severity.

Vaccine attitudes and practices among obstetric providers in New York State following the recommendation for pertussis vaccination during pregnancy

To determine factors associated with obstetric provider recommendation of pertussis vaccine (Tdap) to their pregnant patients following the Advisory Committee on Immunization Practices (ACIP) recommendation that Tdap be given in the third trimester of each pregnancy. Obstetric providers across New York State anonymously completed a standard set of questions to assess vaccine recommendation knowledge and practice. Statistical analysis: Descriptive statistical methods were used to define provider characteristics, knowledge and vaccine practices. Factors associated with recommendation were analyzed using odds ratios. 133 obstetric providers were included in the study. 11% and 13% expressed concern with pertussis vaccine safety and efficacy, respectively, in pregnant women. 92% of obstetric providers stated that they knew ACIP recommendations for Tdap during pregnancy, 80% recommended Tdap to all eligible patients, but only 67% provided Tdap vaccine in their office. Provider knowledge of recommendation (OR 23.33), routine provider recommendation of influenza vaccine (OR 12.5), and administration of pertussis vaccine in the office (OR 7.01) were all factors strongly associated with routine provider recommendation of Tdap vaccine to eligible pregnant women (P < 0.05). Providers expressed concerns with cost of Tdap, the need to administer Tdap with each pregnancy, vaccine safety, low incidence of pertussis in the area, and administration of pertussis vaccine at the hospital after delivery. Educational programs are needed to improve provider vaccine confidence and recommendation.

Community-Centered Education Improves Vaccination Rates in Children From Low-Income Households

OBJECTIVE: We partnered with the Salvation Army to educate resource-poor families regarding childhood immunizations in an effort to improve vaccine coverage rates. METHODS: Eligibility for enrollment included children of families presenting at registration for our Salvation Army holiday gift program, available to families with an annual income <150% of federal poverty guidelines. Parents completed a questionnaire, were provided each child’s vaccination status as documented in the New York State Immunization Information System, and interacted with the study team to address immunization-related concerns. Missed vaccines were identified and parents were directed to their child’s medical home for necessary immunizations. Vaccine coverage was ascertained via the New York State Immunization Information System every 6 to 8 weeks with telephone follow-up for children who remained delayed. The McNemar test and standard 2-proportion comparison were used to determine confidence intervals when analyzing matched or independent data, respectively. RESULTS: A total of 1531 children were enrolled; 416 (28%) of the 1477 children with accurate immunization records were vaccine complete. When we excluded influenza vaccine, 1034 (70%) of children had received all other recommended vaccines. Nine months later, vaccine completion rates increased from 28% to 45%, largely because of improvements in influenza vaccination rates, which increased by 17% (confidence interval [CI] 15.5–19.5), a significant improvement over county (8%, 95% CI 7.4–8.1) and statewide (5%, 95% CI 4.7–4.8) rates during the same period. CONCLUSIONS: Immunization rates in poor children are suboptimal. Partnering with community-based organizations to address parental concerns, provide education, and perform follow-up was effective in improving immunization rates, particularly for influenza vaccine.

Pediatric provider vaccine hesitancy: An under-recognized obstacle to immunizing children

OBJECTIVE To describe vaccine attitudes among pediatric healthcare providers attending immunization conferences. STUDY DESIGN Attendees of 5 American Academy of Pediatrics (AAP)-sponsored vaccine conferences held between June and November 2013 anonymously completed a questionnaire assessing vaccine attitudes and practices prior to the opening of educational sessions. Pearsons chi-square tests and Fishers exact tests were used to analyze associations between vaccine attitudes, vaccine practices and provider characteristics. RESULTS 680 providers attending AAP-sponsored vaccine conferences were included. 661/666 (99%) enrolled providers state they routinely recommend standard pediatric vaccines, yet, 30 (5%) state that they do not routinely recommend influenza and/or human papillomavirus (HPV) vaccines. These providers expressed vaccine safety (87/680 (13%)) and efficacy (21/680 (31%)) concerns and stated belief in vaccine misperceptions: vaccine causes autism (34/668, 5%), multiple vaccines at a single visit reduces vaccine efficacy (43/680, 6%) or overwhelms the immune system (63/680, 9%), and administering HPV vaccine will increase the likelihood of unprotected adolescent sexual activity (29/680, 4%). Six percent of providers who do not routinely recommend all pediatric vaccines correctly identified themselves as vaccine hesitant. CONCLUSION Vaccine hesitancy is under-recognized among pediatric providers attending AAP-sponsored immunization conferences. Educational interventions tailored to address provider vaccine concerns are needed to improve provider vaccine confidence.

Incidence of Invasive Community-Onset Staphylococcus aureus Infections in Children in Central New York

We determined the incidence of invasive community-onset Staphylococcus aureus infections, clinical characteristics, and antibiotic susceptibilities in 128 hospitalized children in central New York. The prevalence of invasive S aureus infections in our institution remained <1% between 1996 and 2006, although the proportion of methicillin-resistant S aureus infections significantly increased.

Practical approaches to vaccine hesitancy issues in the United States: 2013

The intention to delay or avoid vaccines that are recommended by the Advisory Committee on Immunization Practices can be described as “vaccine hesitancy.” While outright refusal of all vaccines is uncommon, hesitancy is seen on a regular basis in most primary care offices, resulting in immunization delay and prolonged susceptibility to preventable disease. The consequences of vaccine hesitancy include the potential for resurgence of vaccine preventable infections. Open, honest, and frank discussions with hesitant patients and their families can assist in their understanding of the importance of vaccines. While many experienced providers are able to do so in an intuitive manner, others may benefit from developing a systemic framework for such discussions. An understanding of the history and rationale for vaccine hesitancy is a first step in regaining lost public confidence in our robust immunization programs.

Prevention of pertussis through adult vaccination

Pertussis is a vaccine preventable respiratory infection. Young infants are at high risk of developing severe complications from infection. Despite high rates of pediatric vaccine uptake, there continues to be increases in pertussis cases, likely due to waning immunity from childhood vaccine and increased transmission through adults. Currently, pertussis booster vaccine (Tdap) is recommended for unimmunized adults and for women in the third trimester of each pregnancy; yet adult Tdap coverage remains low. Administering Tdap vaccine at non-traditional vaccination clinics and at sites where adults are accessing care for their children are effective in improving adult Tdap uptake. While most are willing to receive vaccine when recommended by their provider, lack of provider recommendation is a major obstacle to immunization. Future studies to understand barriers to provider vaccine recommendations need to be undertaken to develop interventions to improve adult Tdap vaccine uptake and reduce pertussis infection in the susceptible population.

Quadrivalent influenza vaccine in the United States.

New strategies to improve influenza vaccines are ongoing. With the recent development of new vaccine formulations, such improvements have begun to materialize in formulations available to providers and their patients. One of the newest strategies developed has been to broaden the composition of the current influenza vaccine formulations from trivalent products to quadrivalent products. To date, three manufacturers have developed and tested four vaccine formulations for safety and immunogenicity. The growing availability of quadrivalent influenza vaccines is now a well-recognized advance among the growing opportunities to improve influenza prevention.