Ashley Fowlkes

Morbid Obesity as a Risk Factor for Hospitalization and Death Due to 2009 Pandemic Influenza A(H1N1) Disease

Background Severe illness due to 2009 pandemic A(H1N1) infection has been reported among persons who are obese or morbidly obese. We assessed whether obesity is a risk factor for hospitalization and death due to 2009 pandemic influenza A(H1N1), independent of chronic medical conditions considered by the Advisory Committee on Immunization Practices (ACIP) to increase the risk of influenza-related complications. Methodology/Principal Findings We used a case-cohort design to compare cases of hospitalizations and deaths from 2009 pandemic A(H1N1) influenza occurring between April–July, 2009, with a cohort of the U.S. population estimated from the 2003–2006 National Health and Nutrition Examination Survey (NHANES); pregnant women and children <2 years old were excluded. For hospitalizations, we defined categories of relative weight by body mass index (BMI, kg/m2); for deaths, obesity or morbid obesity was recorded on medical charts, and death certificates. Odds ratio (OR) of being in each BMI category was determined; normal weight was the reference category. Overall, 361 hospitalizations and 233 deaths included information to determine BMI category and presence of ACIP-recognized medical conditions. Among ≥20 year olds, hospitalization was associated with being morbidly obese (BMI≥40) for individuals with ACIP-recognized chronic conditions (OR = 4.9, 95% CI 2.4–9.9) and without ACIP-recognized chronic conditions (OR = 4.7, 95%CI 1.3–17.2). Among 2–19 year olds, hospitalization was associated with being underweight (BMI≤5th percentile) among those with (OR = 12.5, 95%CI 3.4–45.5) and without (OR = 5.5, 95%CI 1.3–22.5) ACIP-recognized chronic conditions. Death was not associated with BMI category among individuals 2–19 years old. Among individuals aged ≥20 years without ACIP-recognized chronic medical conditions death was associated with obesity (OR = 3.1, 95%CI: 1.5–6.6) and morbid obesity (OR = 7.6, 95%CI 2.1–27.9). Conclusions/Significance Our findings support observations that morbid obesity may be associated with hospitalization and possibly death due to 2009 pandemic H1N1 infection. These complications could be prevented by early antiviral therapy and vaccination.

Decline and Change in Seasonality of US Rotavirus Activity After the Introduction of Rotavirus Vaccine

BACKGROUND: In 2006, routine immunization of US infants against rotavirus was initiated. We assessed national, regional, and local trends in rotavirus testing and detection before and after vaccine introduction. METHODS: We examined data for July 2000 through June 2008 from a national network of ∼70 US laboratories to compare geographical and temporal aspects of rotavirus season timing and peak activity. To assess trends in rotavirus testing and detection, we restricted the analyses to 33 laboratories that reported for ≥26 weeks per season from 2000 to 2008. RESULTS: Nationally, the onset and peak of the 2007–2008 rotavirus season were delayed 15 and 8 weeks, respectively, compared with prevaccine seasons from 2000–2006. Delays were observed in each region. The 2007–2008 rotavirus season lasted 14 weeks compared with a median of 26 weeks during the prevaccine era. Of 33 laboratories, 32 reported fewer positive results and a lower proportion of positive test results in 2007–2008 compared with the median in 2000–2006, with a 67% decline in the number and a 69% decline in the proportion of rotavirus-positive test results. The proportion of positive test results in 2007–2008 compared with the median in 2000–2006 declined >50% in 79% of the laboratories and >75% in 39% of the laboratories. CONCLUSIONS: The 2007–2008 US rotavirus season seems substantially delayed, shorter, and diminished in magnitude compared with seasons before vaccine implementation. The extent of change seems greater than expected on the basis of estimated vaccine coverage, suggesting indirect benefits to unvaccinated individuals. Monitoring in future seasons is needed to confirm these trends.

Monitoring Influenza Activity in the United States: A Comparison of Traditional Surveillance Systems with Google Flu Trends

Background Google Flu Trends was developed to estimate US influenza-like illness (ILI) rates from internet searches; however ILI does not necessarily correlate with actual influenza virus infections. Methods and Findings Influenza activity data from 2003–04 through 2007–08 were obtained from three US surveillance systems: Google Flu Trends, CDC Outpatient ILI Surveillance Network (CDC ILI Surveillance), and US Influenza Virologic Surveillance System (CDC Virus Surveillance). Pearsons correlation coefficients with 95% confidence intervals (95% CI) were calculated to compare surveillance data. An analysis was performed to investigate outlier observations and determine the extent to which they affected the correlations between surveillance data. Pearsons correlation coefficient describing Google Flu Trends and CDC Virus Surveillance over the study period was 0.72 (95% CI: 0.64, 0.79). The correlation between CDC ILI Surveillance and CDC Virus Surveillance over the same period was 0.85 (95% CI: 0.81, 0.89). Most of the outlier observations in both comparisons were from the 2003–04 influenza season. Exclusion of the outlier observations did not substantially improve the correlation between Google Flu Trends and CDC Virus Surveillance (0.82; 95% CI: 0.76, 0.87) or CDC ILI Surveillance and CDC Virus Surveillance (0.86; 95%CI: 0.82, 0.90). Conclusions This analysis demonstrates that while Google Flu Trends is highly correlated with rates of ILI, it has a lower correlation with surveillance for laboratory-confirmed influenza. Most of the outlier observations occurred during the 2003–04 influenza season that was characterized by early and intense influenza activity, which potentially altered health care seeking behavior, physician testing practices, and internet search behavior.

Variation in timing of respiratory syncytial virus outbreaks: lessons from national surveillance.

Respiratory syncytial virus (RSV) is the leading cause of pneumonia and bronchiolitis in infants and children. Immune prophylaxis can reduce the risk of severe RSV disease among some high-risk infants. A summary and update of analyses using National Respiratory and Enteric Virus Surveillance System (NREVSS) data is provided to explore using surveillance data to better define the timing of RSV activity and RSV immune prophylaxis. The methodology used was that outlined in a study by Mullins et al (Pediatr Infect Dis J. 2003;22:857–862), which analyzed weekly antigen detection data reported by laboratories to NREVSS. Data reported to NREVSS between 1990 and 2006 were used to assess seasonality among regional, state, and local areas. Season onset, offset, and duration were calculated for each year and each laboratory, and compared with the U.S. Census region and national median measurements. Results demonstrated a distinct winter peak of RSV activity each year. The extent of variation in the timing of RSV activity in a community from year to year makes it difficult to predict the timing of RSV outbreaks. In addition, the onset timing can vary between communities, even those in close proximity, during the same year. There are, however, regional community patterns that may help guide timing of immune prophylaxis. For example, the South region exhibited an earlier median season onset and longer duration than the other regions, with median onset week 47 and duration 16 weeks. In contrast, the Midwest exhibited a significantly later median onset and shorter duration than the other regions, with median onset week 1 of the following year and duration 13 weeks. Therefore, analyses of NREVSS data show that using surveillance data to tailor the timing of immune prophylaxis precisely will be difficult. Surveillance data can, however, be used to determine how well national patterns represent local patterns. Further analyses are needed to determine how local surveillance data can be used to guide timing of immune prophylaxis.

Evaluation of the Immune Response to a 2-Dose Measles Vaccination Schedule Administered at 6 and 9 Months of Age to HIV-Infected and HIV-Uninfected Children in Malawi

BACKGROUND The World Health Organization recommends that infants at high risk for developing measles before 9 months of age, including human immunodeficiency virus (HIV)-infected infants, receive measles vaccination (MV) at 6 and 9 months of age. METHODS Children born to HIV-infected mothers received MV at 6 and 9 months, and children of HIV-uninfected mothers were randomized to receive MV at 6 and 9 months, MV at 9 months, or routine MV without follow-up. Blood samples were obtained before and 3 months after each MV. Data were collected on adverse events for 21 days after each MV, at all clinic visits, on any hospitalization, and for subjects who died. HIV-infection status was determined by antibody assays and polymerase chain reaction; the presence of measles IgG was determined by EIA. RESULTS Twenty-two hundred mother-infant pairs were enrolled. After the first and second doses of measles vaccine, respectively, the percentages of children who were measles seropositive were 59% (36 of 61) and 64% (29 of 45) among HIV-infected children, 68% (152 of 223) and 94% (189 of 202) among HIV-exposed but uninfected children, and 62% (288 of 467) and 92% (385 of 417) among HIV-unexposed children. Of 521 HIV-unexposed children vaccinated only at 9 months, 398 (76%) were measles seropositive at 12 months. No serious vaccine-related adverse events were identified. CONCLUSIONS An early, 2-dose MV schedule was immunogenic, but a higher proportion of HIV-infected children remained susceptible to measles, compared with HIV-uninfected children (whether HIV exposed or HIV unexposed).

Viruses associated with acute respiratory infections and influenza-like illness among outpatients from the Influenza Incidence Surveillance Project, 2010-2011

Abstract Background. The Influenza Incidence Surveillance Project (IISP) monitored outpatient acute respiratory infection (ARI; defined as the presence of ≥2 respiratory symptoms not meeting ILI criteria) and influenza-like illness (ILI) to determine the incidence and contribution of associated viral etiologies. Methods. From August 2010 through July 2011, 57 outpatient healthcare providers in 12 US sites reported weekly the number of visits for ILI and ARI and collected respiratory specimens on a subset for viral testing. The incidence was estimated using the number of patients in the practice as the denominator, and the virus-specific incidence of clinic visits was extrapolated from the proportion of patients testing positive. Results. The age-adjusted cumulative incidence of outpatient visits for ARI and ILI combined was 95/1000 persons, with a viral etiology identified in 58% of specimens. Most frequently detected were rhinoviruses/enteroviruses (RV/EV) (21%) and influenza viruses (21%); the resulting extrapolated incidence of outpatient visits was 20 and 19/1000 persons respectively. The incidence of influenza virus-associated clinic visits was highest among patients aged 2–17 years, whereas other viruses had varied patterns among age groups. Conclusions. The IISP provides a unique opportunity to estimate the outpatient respiratory illness burden by etiology. Influenza virus infection and RV/EV infection(s) represent a substantial burden of respiratory disease in the US outpatient setting, particularly among children.

Increased Activity of Coxsackievirus B1 Strains Associated with Severe Disease among Young Infants in the United States, 2007—2008

BACKGROUND Enterovirus infections are very common and typically cause mild illness, although neonates are at higher risk for severe illness. In 2007, the Centers for Disease Control and Prevention (CDC) received multiple reports of severe neonatal illness and death associated with coxsackievirus B1 (CVB1), a less common enterovirus serotype not previously associated with death in surveillance reports to the CDC. METHODS This report includes clinical, epidemiologic, and virologic data from cases of severe neonatal illness associated with CVB1 reported during the period from 2007 through 2008 to the National Enterovirus Surveillance System (NESS), a voluntary, passive surveillance system. Also included are data on additional cases reported to the CDC outside of the NESS. Virus isolates or original specimens obtained from patients from 25 states were referred to the CDC picornavirus laboratory for molecular typing or characterization. RESULTS During 2007-2008, the NESS received 1079 reports of enterovirus infection. CVB1 accounted for 176 (23%) of 775 reported cases with known serotype, making it the most commonly reported serotype for the first time ever in the NESS. Six neonatal deaths due to CVB1 infection were also reported to the CDC during that time. Phylogenetic analysis of the 2007 and 2008 CVB1 strains indicated that the increase in cases resulted from widespread circulation of a single genetic lineage that had been present in the United States since at least 2001. CONCLUSIONS Healthcare providers and public health departments should be vigilant to the possibility of continuing CVB1-associated neonatal illness, and testing and continued reporting of enterovirus infections should be encouraged.

Incidence of medically attended influenza during pandemic and post-pandemic seasons through the Influenza Incidence Surveillance Project, 2009–13

BACKGROUND Since the introduction of pandemic influenza A (H1N1) to the USA in 2009, the Influenza Incidence Surveillance Project has monitored the burden of influenza in the outpatient setting through population-based surveillance. METHODS From Oct 1, 2009, to July 31, 2013, outpatient clinics representing 13 health jurisdictions in the USA reported counts of influenza-like illness (fever including cough or sore throat) and all patient visits by age. During four years, staff at 104 unique clinics (range 35-64 per year) with a combined median population of 368,559 (IQR 352,595-428,286) attended 35,663 patients with influenza-like illness and collected 13,925 respiratory specimens. Clinical data and a respiratory specimen for influenza testing by RT-PCR were collected from the first ten patients presenting with influenza-like illness each week. We calculated the incidence of visits for influenza-like illness using the size of the patient population, and the incidence attributable to influenza was extrapolated from the proportion of patients with positive tests each week. FINDINGS The site-median peak percentage of specimens positive for influenza ranged from 58.3% to 77.8%. Children aged 2 to 17 years had the highest incidence of influenza-associated visits (range 4.2-28.0 per 1000 people by year), and adults older than 65 years had the lowest (range 0.5-3.5 per 1000 population). Influenza A H3N2, pandemic H1N1, and influenza B equally co-circulated in the first post-pandemic season, whereas H3N2 predominated for the next two seasons. Of patients for whom data was available, influenza vaccination was reported in 3289 (28.7%) of 11,459 patients with influenza-like illness, and antivirals were prescribed to 1644 (13.8%) of 11,953 patients. INTERPRETATION Influenza incidence varied with age groups and by season after the pandemic of 2009 influenza A H1N1. High levels of influenza virus circulation, especially in young children, emphasise the need for additional efforts to increase the uptake of influenza vaccines and antivirals. FUNDING US Centers for Disease Control and Prevention.

Limited duration of vaccine poliovirus and other enterovirus excretion among human immunodeficiency virus infected children in Kenya

BackgroundImmunodeficient persons with persistent vaccine-related poliovirus infection may serve as a potential reservoir for reintroduction of polioviruses after wild poliovirus eradication, posing a risk of their further circulation in inadequately immunized populations.MethodsTo estimate the potential for vaccine-related poliovirus persistence among HIV-infected persons, we studied poliovirus excretion following vaccination among children at an orphanage in Kenya. For 12 months after national immunization days, we collected serial stool specimens from orphanage residents aged <5 years at enrollment and recorded their HIV status and demographic, clinical, immunological, and immunization data. To detect and characterize isolated polioviruses and non-polio enteroviruses (NPEV), we used viral culture, typing and intratypic differentiation of isolates by PCR, ELISA, and nucleic acid sequencing. Long-term persistence was defined as shedding for ≥ 6 months.ResultsTwenty-four children (15 HIV-infected, 9 HIV-uninfected) were enrolled, and 255 specimens (170 from HIV-infected, 85 from HIV-uninfected) were collected. All HIV-infected children had mildly or moderately symptomatic HIV-disease and moderate-to-severe immunosuppression. Fifteen participants shed vaccine-related polioviruses, and 22 shed NPEV at some point during the study period. Of 46 poliovirus-positive specimens, 31 were from HIV-infected, and 15 from HIV-uninfected children. No participant shed polioviruses for ≥ 6 months. Genomic sequencing of poliovirus isolates did not reveal any genetic evidence of long-term shedding. There was no long-term shedding of NPEV.ConclusionThe results indicate that mildly to moderately symptomatic HIV-infected children retain the ability to clear enteroviruses, including vaccine-related poliovirus. Larger studies are needed to confirm and generalize these findings.

Persistence of Vaccine-Induced Measles Antibody Beyond Age 12 Months: A Comparison of Response to One and Two Doses of Edmonston-Zagreb Measles Vaccine Among HIV-Infected and Uninfected Children in Malawi

BACKGROUND Previously, we demonstrated that measles antibody prevalence was lower at age 12 months among children infected with human immunodeficiency virus (HIV) than uninfected children following measles vaccination (MV) at ages 6 and 9 months. Among HIV-uninfected children, measles antibody prevalence was lower among 1- than 2-dose MV recipients. Here, we report results through age 24 months. METHODS Children born to HIV-infected mothers received MV at 6 and 9 months, and children of HIV-uninfected mothers were randomized to MV at 6 and 9 months or MV at 9 months. We followed children through age 24 months. The childs HIV status was determined and measles immunoglobulin G (IgG) level was measured by enzyme immunoassay (EIA) and by plaque reduction neutralization (PRN) on a subset. RESULTS Among HIV-uninfected children, the difference in measles antibody prevalence at age 12 months between one- and two-dose recipients reported previously by EIA was shown to be smaller by PRN. By age 24 months, 84% and 87% of HIV-uninfected children receiving 1 or 2 doses, respectively, were seroprotected. Only 41% of 22 HIV-infected children were measles seroprotected at age 20 months. DISCUSSION Measles seroprotection persisted through age 24 months among HIV-uninfected children who received 1 or 2 doses of MV. HIV-infected children demonstrated seroprotection through age 12 months, but this was not sustained.