Catherine A. Panozzo

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.

Demographic Variability, Vaccination, and the Spatiotemporal Dynamics of Rotavirus Epidemics

Ecology of Diarrhea Rotavirus is an important cause of morbidity and mortality globally, and, although the infection takes a terrible toll on infant lives, its epidemiology is rather poorly known. New vaccines have become available and are being introduced in the United States prior to global rollout, but they may have some unexpected effects on disease dynamics. Pitzer et al. (p. 290; see the Perspective by Medley and Nokes) analyzed data and developed models describing the epidemiology of rotavirus before and during adoption of the vaccine. Ecological analysis showed that the birth rate predicted the timing of epidemics much better than climatic variables and that shifts in birth rates explained changes over the years. But as increasing numbers of infants are vaccinated, the pool of susceptible individuals in the population will be reduced, which will affect the annual waves of geographic spread of rotavirus. Diarrhea-causing rotavirus epidemics can be predicted by shifts in birth rate rather than by seasonal variables. Historically, annual rotavirus activity in the United States has started in the southwest in late fall and ended in the northeast 3 months later; this trend has diminished in recent years. Traveling waves of infection or local environmental drivers cannot account for these patterns. A transmission model calibrated against epidemiological data shows that spatiotemporal variation in birth rate can explain the timing of rotavirus epidemics. The recent large-scale introduction of rotavirus vaccination provides a natural experiment to further test the impact of susceptible recruitment on disease dynamics. The model predicts a pattern of reduced and lagged epidemics postvaccination, closely matching the observed dynamics. Armed with this validated model, we explore the relative importance of direct and indirect protection, a key issue in determining the worldwide benefits of vaccination.

Sustained decline in rotavirus detections in the United States following the introduction of rotavirus vaccine in 2006.

Background: Following implementation of the rotavirus vaccination program in 2006, rotavirus activity in the United States declined dramatically in 2007–2008 but increased slightly in 2008–2009, despite greater vaccine uptake. To further evaluate impact of the vaccine program, we assessed trends in rotavirus testing and detection during 2009–2010. Methods: We examined rotavirus testing data from July 2000 to June 2010 from the National Respiratory and Enteric Viruses Surveillance System to compare rotavirus season timing and peak activity in the pre- and postvaccine introduction eras. Rotavirus season onset was defined as the first of 2 consecutive weeks during which the percentage of specimens testing positive for rotavirus was ≥10%. To assess trends in rotavirus testing and detection, we restricted the analyses to 25 laboratories that reported for ≥26 weeks per season from 2000 to 2010. Results: During 2009–2010, the threshold for the start of the rotavirus season was never achieved nationally or in the North, Midwest, or West. Activity in the South met this threshold but the season duration was substantially shorter and of lower magnitude than in all previous pre- and postvaccine introduction seasons. Nationally and within each region, the peak week was more delayed and the peak proportion of positive tests was substantially lower than all previous seasons. The total number of tests performed declined by 23%, and the number of positive tests declined by 86%. Conclusions: Rotavirus activity was substantially diminished during the 2009–2010 rotavirus season compared with the prevaccine baseline and the 2 previous postvaccine introduction seasons. These sustained declines over 3 rotavirus seasons reaffirm the health benefits of the US rotavirus vaccination program.

Outbreak of severe respiratory disease associated with emergent human adenovirus serotype 14 at a US Air Force training facility in 2007.

BACKGROUND In 2007, a US Air Force training facility reported a cluster of severe respiratory illnesses associated with a rare human adenovirus (Ad) serotype, Ad14. We investigated this outbreak to better understand its epidemiology, clinical spectrum, and associated risk factors. METHODS Data were collected from ongoing febrile respiratory illness (FRI) surveillance and from a retrospective cohort investigation. Because an Ad7 vaccine is in development, Ad7 antibody titers in pretraining serum samples from trainees with mild and those with severe Ad14 illness were compared. RESULTS During 2007, an estimated 551 (48%) of 1147 trainees with FRI were infected with Ad14; 23 were hospitalized with pneumonia, 4 required admission to an intensive care unit, and 1 died. Among cohort members (n = 173), the Ad14 infection rate was high (50%). Of those infected, 40% experienced FRI. No cohort members were hospitalized. Male sex (risk ratio [RR], 4.7 [95% confidence interval {CI}, 2.2-10.1]) and an ill close contact (RR, 1.6 [95% CI, 1.2-2.2]) were associated with infection. Preexisting Ad7 neutralizing antibodies were found in 7 (37%) of 19 Ad14-positive trainees with mild illness but in 0 of 16 trainees with Ad14 pneumonia (P = .007). CONCLUSIONS Emergence of Ad14, a rare Ad serotype, caused a protracted outbreak of respiratory illness among military recruits. Most infected recruits experienced FRI or milder illnesses. Some required hospitalization, and 1 died. Natural Ad7 infection may protect against severe Ad14 illness.

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.

A Cross-Sectional Study of HPV Vaccine Acceptability in Gaborone, Botswana

Background Cervical cancer is the most common cancer among women in Botswana and elsewhere in Sub-Saharan Africa. We sought to examine whether HPV vaccine is acceptable among parents in Botswana, which recently licensed the vaccine to prevent cervical cancer. Methods and Findings We conducted a cross-sectional survey in 2009, around the time the vaccine was first licensed, with adults recruited in general medicine and HIV clinics in Gaborone, the capital of Botswana. Although only 9% (32/376) of respondents had heard of HPV vaccine prior to the survey, 88% (329/376) said they definitely will have their adolescent daughters receive HPV vaccine. Most respondents would get the vaccine for their daughters at a public or community clinic (42%) or a gynecology or obstetricians office (39%), and 74% would get it for a daughter if it were available at her school. Respondents were more likely to say that they definitely will get HPV vaccine for their daughters if they had less education (OR = 0.20, 95% CI = 0.07–0.58) or lived more than 30 kilometers from the capital, Gaborone (OR = 2.29, 95% CI = 1.06–4.93). Other correlates of acceptability were expecting to be involved in the decision to get HPV vaccine, thinking the vaccine would be hard to obtain, and perceiving greater severity of HPV-related diseases. Conclusions HPV vaccination of adolescent girls would be highly acceptable if the vaccine became widely available to the daughters of healthcare seeking parents in Gaborone, Botswana. Potential HPV vaccination campaigns should provide more information about HPV and the vaccine as well as work to minimize barriers.

Outbreak of Pneumonia Associated with Emergent Human Adenovirus Serotype 14—Southeast Alaska, 2008

BACKGROUND In September 2008, an outbreak of pneumonia associated with an emerging human adenovirus (human adenovirus serotype 14 [HAdV-14]) occurred on a rural Southeast Alaska island. Nine patients required hospitalization, and 1 patient died. METHODS To investigate the outbreak, pneumonia case patients were matched to control participants on the basis of age, sex, and community of residence. Participants in the investigation and their household contacts were interviewed, and serum samples and respiratory tract specimens were collected. Risk factors were evaluated by means of conditional logistic regression. RESULTS Among 32 pneumonia case patients, 21 (65%) had confirmed or probable HAdV-14 infection. None of 32 matched control participants had evidence of HAdV-14 infection (P<.001 for the difference). Factors independently associated with pneumonia included contact with a known HAdV-14-infected case patient (odds ratio [OR], 18.3 [95% confidence interval {CI}, >or=2.0]), current smoking (OR, 6.7 [95% CI, >or=0.9]), and having neither traveled off the island nor attended a large public gathering (OR, 14.7 [95% CI, >or=2.0]). Fourteen (67%) of 21 HAdV-14-positive case patients belonged to a single network of people who socialized and often smoked together and infrequently traveled off the island. HAdV-14 infection occurred in 43% of case-patient household contacts, compared with 5% of control-participant household contacts (P = .005). CONCLUSIONS During a community outbreak in Alaska, HAdV-14 appeared to have spread mostly among close contacts and not widely in the community. Demographic characteristics and illness patterns among the case patients were similar to those observed in other recent outbreaks of HAdV-14 infection in the United States.

Invasive pneumococcal pneumonia and respiratory virus co-infections.

Each year, especially in the winter, many get sick and some die of invasive pneumococcal pneumonia. Does this type of pneumonia increase in the winter because people are in closer contact indoors? Or are people more susceptible to this bacterial disease after having had a seasonal respiratory virus infection? A season-by-season analysis found an association between pneumococcal pneumonia and two viruses (influenza and respiratory syncytial virus). The association varied by season and was strongest when the predominant influenza virus subtype was H3N2. Vaccination against influenza and RSV should also help protect against pneumococcal pneumonia.

Use of Respiratory Syncytial Virus Surveillance Data to Optimize the Timing of Immunoprophylaxis

OBJECTIVE: For children in the United States who are at high risk for severe respiratory syncytial virus (RSV) infection, the American Academy of Pediatrics (AAP) recommends administering immunoprophylaxis during the RSV season. We present an approach to using surveillance data to help guide application of AAP recommendations for immunoprophylaxis to local patterns of RSV outbreaks. METHODS: We analyzed data from laboratories that report consistently to the National Respiratory and Enteric Virus Surveillance System from 1992 to 2007. Local RSV seasons were defined and an immunoprophylaxis schedule was determined by using the median onset dates from each laboratory during 2002–2007. We applied these dates to 10 preceding years of RSV detection data. We compared how well the 5-year median-based method and a fixed date method were able to match the timing of immunoprophylaxis to the RSV season. RESULTS: Nineteen laboratories met our inclusion criteria and generally experienced only 1 RSV outbreak per season. Five years of data gave similar median onset/offset dates and season duration, as did 10 years and 15 years of data. The 5-year median schedule increased the number of seasons that children were protected at the season onset by 15% compared with a fixed start date of November 1 and identified communities that experienced RSV seasons with extended durations. CONCLUSIONS: The 5-year median method can be used to characterize timing of RSV seasons and optimally apply the current AAP recommendations for timing of palivizumab prophylaxis to the local community.

Evaluation of an intervention providing HPV vaccine in schools.

OBJECTIVES To conduct outcome and process evaluations of school-located HPV vaccination clinics in partnership with a local health department. METHODS Temporary clinics provided the HPV vaccine to middle school girls in Guilford County, North Carolina, in 2009-2010. RESULTS HPV vaccine initiation was higher among girls attending host schools than satellite schools (6% vs. 1%, OR = 6.56, CI = 3.99-10.78). Of the girls who initiated HPV vaccine, 80% received all 3 doses. Private insurance or federal programs paid for most vaccine doses. CONCLUSIONS Lessons learned for creating more effective school-health department partnerships include focusing on host schools and delivering several vaccines to adolescents, not just HPV vaccine alone.