Paul Gargiullo

Cross-Reactive Antibody Responses to the 2009 Pandemic H1N1 Influenza Virus

BACKGROUND A new pandemic influenza A (H1N1) virus has emerged, causing illness globally, primarily in younger age groups. To assess the level of preexisting immunity in humans and to evaluate seasonal vaccine strategies, we measured the antibody response to the pandemic virus resulting from previous influenza infection or vaccination in different age groups. METHODS Using a microneutralization assay, we measured cross-reactive antibodies to pandemic H1N1 virus (2009 H1N1) in stored serum samples from persons who either donated blood or were vaccinated with recent seasonal or 1976 swine influenza vaccines. RESULTS A total of 4 of 107 persons (4%) who were born after 1980 had preexisting cross-reactive antibody titers of 40 or more against 2009 H1N1, whereas 39 of 115 persons (34%) born before 1950 had titers of 80 or more. Vaccination with seasonal trivalent inactivated influenza vaccines resulted in an increase in the level of cross-reactive antibody to 2009 H1N1 by a factor of four or more in none of 55 children between the ages of 6 months and 9 years, in 12 to 22% of 231 adults between the ages of 18 and 64 years, and in 5% or less of 113 adults 60 years of age or older. Seasonal vaccines that were formulated with adjuvant did not further enhance cross-reactive antibody responses. Vaccination with the A/New Jersey/1976 swine influenza vaccine substantially boosted cross-reactive antibodies to 2009 H1N1 in adults. CONCLUSIONS Vaccination with recent seasonal nonadjuvanted or adjuvanted influenza vaccines induced little or no cross-reactive antibody response to 2009 H1N1 in any age group. Persons under the age of 30 years had little evidence of cross-reactive antibodies to the pandemic virus. However, a proportion of older adults had preexisting cross-reactive antibodies.

Intussusception among Infants Given an Oral Rotavirus Vaccine

BACKGROUND Intussusception is a form of intestinal obstruction in which a segment of the bowel prolapses into a more distal segment. Our investigation began on May 27, 1999, after nine cases of infants who had intussusception after receiving the tetravalent rhesus-human reassortant rotavirus vaccine (RRV-TV) were reported to the Vaccine Adverse Event Reporting System. METHODS In 19 states, we assessed the potential association between RRV-TV and intussusception among infants at least 1 but less than 12 months old. Infants hospitalized between November 1, 1998, and June 30, 1999, were identified by systematic reviews of medical and radiologic records. Each infant with intussusception was matched according to age with four healthy control infants who had been born at the same hospital as the infant with intussusception. Information on vaccinations was verified by the provider. RESULTS Data were analyzed for 429 infants with intussusception and 1763 matched controls in a case-control analysis as well as for 432 infants with intussusception in a case-series analysis. Seventy-four of the 429 infants with intussusception (17.2 percent) and 226 of the 1763 controls (12.8 percent) had received RRV-TV (P=0.02). An increased risk of intussusception 3 to 14 days after the first dose of RRV-TV was found in the case-control analysis (adjusted odds ratio, 21.7; 95 percent confidence interval, 9.6 to 48.9). In the case-series analysis, the incidence-rate ratio was 29.4 (95 percent confidence interval, 16.1 to 53.6) for days 3 through 14 after a first dose. There was also an increase in the risk of intussusception after the second dose of the vaccine, but it was smaller than the increase in risk after the first dose. Assuming full implementation of a national program of vaccination with RRV-TV, we estimated that 1 case of intussusception attributable to the vaccine would occur for every 4670 to 9474 infants vaccinated. CONCLUSIONS The strong association between vaccination with RRV-TV and intussusception among otherwise healthy infants supports the existence of a causal relation. Rotavirus vaccines with an improved safety profile are urgently needed.

Intussusception Risk and Health Benefits of Rotavirus Vaccination in Mexico and Brazil

BACKGROUND Because postlicensure surveillance determined that a previous rotavirus vaccine, RotaShield, caused intussusception in 1 of every 10,000 recipients, we assessed the association of the new monovalent rotavirus vaccine (RV1) with intussusception after routine immunization of infants in Mexico and Brazil. METHODS We used case-series and case-control methods to assess the association between RV1 and intussusception. Infants with intussusception were identified through active surveillance at 69 hospitals (16 in Mexico and 53 in Brazil), and age-matched infants from the same neighborhood were enrolled as controls. Vaccination dates were verified by a review of vaccination cards or clinic records. RESULTS We enrolled 615 case patients (285 in Mexico and 330 in Brazil) and 2050 controls. An increased risk of intussusception 1 to 7 days after the first dose of RV1 was identified among infants in Mexico with the use of both the case-series method (incidence ratio, 5.3; 95% confidence interval [CI], 3.0 to 9.3) and the case-control method (odds ratio, 5.8; 95% CI, 2.6 to 13.0). No significant risk was found after the first dose among infants in Brazil, but an increased risk, albeit smaller than that seen after the first dose in Mexico--an increase by a factor of 1.9 to 2.6 - was seen 1 to 7 days after the second dose. A combined annual excess of 96 cases of intussusception in Mexico (approximately 1 per 51,000 infants) and in Brazil (approximately 1 per 68,000 infants) and of 5 deaths due to intussusception was attributable to RV1. However, RV1 prevented approximately 80,000 hospitalizations and 1300 deaths from diarrhea each year in these two countries. CONCLUSIONS RV1 was associated with a short-term risk of intussusception in approximately 1 of every 51,000 to 68,000 vaccinated infants. The absolute number of deaths and hospitalizations averted because of vaccination far exceeded the number of intussusception cases that may have been associated with vaccination. (Funded in part by the GAVI Alliance and the U.S. Department of Health and Human Services.).

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.

Changing Varicella Epidemiology in Active Surveillance Sites—United States, 1995–2005

Significant reductions in varicella incidence were reported from 1995 to 2000 in the varicella active surveillance sites of Antelope Valley (AV), California, and West Philadelphia (WP), Pennsylvania. We examined incidence rates, median age, and vaccination status of case patients for 1995-2005. Coverage data were from the National Immunization Survey. By 2005, coverage among children 19-35 months of age reached 92% (AV) and 94% (WP); 57% and 64% of case patients in AV and WP, respectively, were vaccinated; and varicella incidence declined by 89.8% in AV and 90.4% in WP. Incidence declined in all age groups, especially among children <10 years of age in both sites and among adolescents 10-14 years of age in WP. In AV, since 2000, the incidence among adolescents 10-14 and 15-19 years of age increased. Implementation of school requirements through 10th grade in WP may explain the differences in the decline in incidence among adolescents. Continued surveillance will be important to monitor the impact that the 2-dose vaccine policy in children has on varicella epidemiology.

Influenza vaccination in children with asthma in Health Maintenance Organizations

We assessed vaccination coverage and predictors of influenza vaccination in asthmatic children in four large Health Maintenance Organizations. We studied 68,839 children with asthma at four Health Maintenance Organizations (HMOs) in the 1995-1996 influenza season and 34,032 children at two HMOs in the 1996-1997 influenza season. In both seasons only 9-10% were vaccinated against influenza. Children who were hospitalized, had an emergency department visit for asthma or a prescription for a beta-agonist prior to the influenza season, were more likely to be vaccinated. Overall, 61% of the unvaccinated asthmatic children had made an outpatient clinic visit during months when influenza vaccination would have been appropriate. Vaccination coverage could be increased by taking advantage of all opportunities to vaccinate children with asthma whenever they make clinic visits in the fall and early winter.

Risk Factors for Severe Illness with 2009 Pandemic Influenza A (H1N1) Virus Infection in China

BACKGROUND Data on risk factors for severe outcomes from 2009 pandemic influenza A (H1N1) virus infection are limited outside of developed countries. METHODS We reviewed medical charts to collect data from patients hospitalized with laboratory-confirmed 2009 H1N1 infection who were identified across China during the period from September 2009 through February 2010, and we analyzed potential risk factors associated with severe illness (defined as illness requiring intensive care unit admission or resulting in death). RESULTS Among 9966 case patients, the prevalence of chronic medical conditions (33% vs 14%), pregnancy (15% vs 7%), or obesity (19% vs 14%) was significantly higher in those patients with severe illness than it was in those with less severe disease. In multivariable analyses, among nonpregnant case patients aged ≥ 2 years, having a chronic medical condition significantly increased the risk of severe outcome among all age groups, and obesity was a risk factor among those <60 years of age. The risk of severe illness among pregnant case patients was significantly higher for those in the second and third trimesters. The risk of severe illness was increased when oseltamivir treatment was initiated ≥ 5 days after illness onset (odds ratio, 1.42; 95% confidence interval, 1.20-1.67). For persons <60 years of age, the prevalence of obesity among case patients with severe illness was significantly greater than it was among those without severe illness or among the general population. CONCLUSIONS Risk factors for severe 2009 H1N1 illness in China were similar to those observed in developed countries, but there was a lower prevalence of chronic medical conditions and a lower prevalence of obesity. Obesity was a risk factor among case patients < 60 years of age. Early initiation of oseltamivir treatment was most beneficial, and there was an increased risk of severe disease when treatment was started ≥ 5 days after illness onset.

The incidence and clinical characteristics of herpes zoster among children and adolescents after implementation of varicella vaccination.

Background: The varicella-zoster virus (VZV) vaccine strain may reactivate to cause herpes zoster. Limited data suggest that the risk of herpes zoster in vaccinated children could be lower than in children with naturally acquired varicella. We examine incidence trends, risk and epidemiologic and clinical features of herpes zoster disease among children and adolescents by vaccination status. Methods: Population-based active surveillance was conducted among <20 years old residents in Antelope Valley, California, from 2000 through 2006. Structured telephone interviews collected demographic, varicella vaccination and disease histories, and clinical information. Results: From 2000 to 2006, the incidence of herpes zoster among children <10 years of age declined by 55%, from 42 cases reported in 2000 (74.8/100,000 persons; 95% confidence interval [95% CI]: 55.3–101.2) to 18 reported in 2006 (33.3/100,000; 95% CI: 20.9–52.8; P < 0.001). During the same period, the incidence of herpes zoster among 10- to 19-year-olds increased by 63%, from 35 cases reported in 2000 (59.5/100,000 persons; 95% CI: 42.7–82.9) to 64 reported in 2006 (96.7/100,000; 95% CI: 75.7–123.6; P < 0.02). Among children aged <10 years, those with a history of varicella vaccination had a 4 to 12 times lower risk for developing herpes zoster compared with children with history of varicella disease. Conclusions: Varicella vaccine substantially decreases the risk of herpes zoster among vaccinated children and its widespread use will likely reduce overall herpes zoster burden in the United States. The increase in herpes zoster incidence among 10- to 19-year-olds could not be confidently explained and needs to be confirmed from other data sources.

Building the infrastructure for nationwide cancer surveillance and control--a comparison between the National Program of Cancer Registries (NPCR) and the Surveillance, Epidemiology, and End Results (SEER) Program (United States).

Objective: In preparation for jointly publishing official government cancer statistics, the Centers for Disease Control and Prevention (CDC) and the National Cancer Institute (NCI) compared incidence rates from NCIs Surveillance Epidemiology and End Results (SEER) program and CDCs National Program of Cancer Registries (NPCR). Methods: Data for 1999 covering 78% of the US population were obtained from SEER and selected NPCR registries that met high quality data criteria. incidence rates (per 100,000 population) were age-adjusted to the 2000 US standard population, and 95% gamma confidence intervals were estimated Results: NPCR rates for all sites combined were higher than SEER rates (males: NPCR 553.6, SEER 538.7; females: NPCR 420.8, SEER 412.5), but rates for specific cancer sites varied by registry program. Rates for colon cancer (males: NPCR 47.0, SEER 42.7; females: NPCR 36.5, SEER 33.8) and tobacco-related cancers were higher in NPCR than SEER. In contrast, NPCR rates were lower than SEER rates for cancers of the female breaset (NPCR 134.0, SEER 135.9), prostate (NPCR 162.0, SEER 170.2), and melanoma as well as for cancers more common among Asians and Pacific Islanders (e.g., stomach cancer).Conclusions: Rate differences may arise from population difference in socio-demographic characteristics, screening use, health behaviors, exposure to cancer causing agents or registry operations factors.

Influenza Illness and Hospitalizations Averted by Influenza Vaccination in the United States, 2005-2011

Context The goal of influenza vaccination programs is to reduce influenza-associated disease outcomes. Therefore, estimating the reduced burden of influenza as a result of vaccination over time and by age group would allow for a clear understanding of the value of influenza vaccines in the US, and of areas where improvements could lead to greatest benefits. Objective To estimate the direct effect of influenza vaccination in the US in terms of averted number of cases, medically-attended cases, and hospitalizations over six recent influenza seasons. Design Using existing surveillance data, we present a method for assessing the impact of influenza vaccination where impact is defined as either the number of averted outcomes or as the prevented disease fraction (the number of cases estimated to have been averted relative to the number of cases that would have occurred in the absence of vaccination). Results We estimated that during our 6-year study period, the number of influenza illnesses averted by vaccination ranged from a low of approximately 1.1 million (95% confidence interval (CI) 0.6–1.7 million) during the 2006–2007 season to a high of 5 million (CI 2.9–8.6 million) during the 2010–2011 season while the number of averted hospitalizations ranged from a low of 7,700 (CI 3,700–14,100) in 2009–2010 to a high of 40,400 (CI 20,800–73,000) in 2010–2011. Prevented fractions varied across age groups and over time. The highest prevented fraction in the study period was observed in 2010–2011, reflecting the post-pandemic expansion of vaccination coverage. Conclusions Influenza vaccination programs in the US produce a substantial health benefit in terms of averted cases, clinic visits and hospitalizations. Our results underscore the potential for additional disease prevention through increased vaccination coverage, particularly among nonelderly adults, and increased vaccine effectiveness, particularly among the elderly.