Abrupt emergence of diverse species B adenoviruses at US military recruit training centers.

BACKGROUND: Adenoviruses (Ads) cause continuous outbreaks of acute respiratory disease (ARD) in US military training facilities. In 1996, the loss of vaccines targeting the dominant recruit-associated serotypes precipitated the reemergence of Ads in these populations. Between 1999 and 2002, serotype 4 accounted for >95% of Ads isolated from recruits and for >50% of ARD cases in training facilities (15,000 cases/year). METHODS: Ads (n=1867) collected between 2002 and 2006 from recruits with ARD at 8 military training facilities in the United States were serotyped by serum neutralization and polymerase chain reaction. RESULTS: The dominance of Ad4 continued through 2005, followed by a simultaneous emergence of diverse species B serotypes at the majority of sites. This included the subspecies B1 serotypes 3, 7, and 21 and the subspecies B2 serotype 14. Ad14 was the most prevalent species B serotype, appearing in high numbers at 3 sites and becoming dominant at 1. CONCLUSIONS: Subspecies B2 Ads have rarely been associated with ARD, and only in Eurasia. This survey represents the first report of AdB2-associated ARD in the Western Hemisphere. The simultaneous emergence of several species B Ads suggests a common external source (the civilian population) and a decrease in preexisting immunity to species B Ads.

Influenza vaccine effectiveness among US military basic trainees, 2005-06 season.

Virtually all US military basic trainees receive seasonal influenza vaccine. Surveillance data collected from December 2005 through March 2006 were evaluated to estimate effectiveness of the influenza vaccine at 6 US military basic training centers. Vaccine effectiveness against laboratory-confirmed influenza was 92% (95% confidence interval 85%-96%).

Diagnostic discrimination of live attenuated influenza vaccine strains and community-acquired pathogenic strains in clinical samples.

Live vaccines can generate false-positive results on common influenza assays including reverse transcriptase-PCR (RT-PCR), culture and antigen tests. This threatens the integrity of epidemiological data and may misdirect treatment and control efforts. We report the development of RT-PCR tests that distinguish live FluMist vaccine (FMV) strains from circulating influenza strains in clinical samples. Primers were validated using influenza-positive samples from unvaccinated patients, packaged FMV, and one PCR-positive asymptomatic vaccine. Furthermore, the assay was used to experimentally test our lab's collection of influenza-positive samples from the 2004-05 and 2005-06 influenza seasons and several 2005 preseason isolates to determine the rate of vaccine-derived false-positive results under differing epidemiological conditions. Analytical and clinical validations show that the assay is both sensitive and specific. Experimental results demonstrate that 51 out of 51 influenza-positive samples collected during influenza season from ill, previously-vaccinated military personnel represent real infections with circulating strains. Finally, the assay shows that four preseason influenza-positive samples were false positives resulting from vaccine shedding. The vaccine-discriminatory RT-PCR methods described here provide the first test designed to distinguish FMV strains from circulating strains. The results show that the test is effective, and demonstrate the importance of such tests in the age of live vaccines.

Co-infections of adenovirus species in previously vaccinated patients.

Despite the success of the adenovirus vaccine administered to US military trainees, acute respiratory disease (ARD) surveillance still detected breakthrough infections (respiratory illnesses associated with the adenovirus serotypes specifically targeted by the vaccine). To explore the role of adenoviral co-infection (simultaneous infection by multiple pathogenic adenovirus species) in breakthrough disease, we examined specimens from patients with ARD by using 3 methods to detect multiple adenoviral species: a DNA microarray, a polymerase chain reaction (PCR)-enzyme-linked immunosorbent assay, and a multiplex PCR assay. Analysis of 52 samples (21 vaccinated, 31 unvaccinated) collected from 1996 to 2000 showed that all vaccinated samples had co-infections. Most of these co-infections were community-acquired serotypes of species B1 and E. Unvaccinated samples primarily contained only 1 species (species E) associated with adult respiratory illness. This study highlights the rarely reported phenomenon of adenoviral co-infections in a clinically relevant environment suitable for the generation of new recombinational variants.

Vaccine-preventable adenoviral respiratory illness in US military recruits, 1999-2004.

BACKGROUND AND METHODS: The high burden of respiratory infections in military populations is well documented throughout history. The primary pathogen responsible for morbidity among US recruits in training was shown to be adenovirus. Highly efficacious oral vaccines were used for 25 years, but vaccine production ceased in 1996, and available stores were depleted by early 1999. Surveillance for acute febrile respiratory illness was performed at eight military recruit training sites throughout the United States from July 1999 through June 2004 to document rates after loss of the vaccines. Laboratory diagnoses complimented the surveillance efforts. RESULTS: Over the 5 years, nearly 12 million person-weeks were followed and an estimated 110,172 febrile respiratory illness cases and 73,748 adenovirus cases were identified. Rates of illness were highest at the Navy and Air Force training centers, with average annual rates of 1.20 and 1.35 cases per 100 recruit-weeks, respectively. Adenoviral-associated illness rates peaked in weeks 3-5 of training, depending upon service. CONCLUSIONS: The burden of adenoviral illness among US recruit populations has returned to high levels since loss of the vaccines. Restoration of an effective adenovirus vaccine effort within the military is anticipated by 2008, potentially reducing the adenovirus morbidity suffered in this vulnerable population. Efforts to determine the burden of adenovirus and potential benefits of vaccination in civilian populations are being renewed.

Effectiveness of the 2003-2004 influenza vaccine among U.S. military basic trainees: a year of suboptimal match between vaccine and circulating strain.

Effectiveness of the 2003-2004 influenza vaccine was evaluated at five military basic training centers throughout the United States. Data from surveillance conducted in December and January 2003-2004 in this highly vaccinated population were evaluated. During this period, 10.6% (37/350) of specimens were positive for influenza A. A 14-day period after vaccination was considered the period prior to immune protection; vaccine effectiveness (VE) was calculated based on febrile respiratory illness presentation and laboratory confirmation of influenza before or after this 14-day period. Thirty-two cases presented within 14 days of vaccination, and five cases presented beyond 14 days from vaccination. VE in this population was estimated to be 94.4% for laboratory-confirmed influenza. In contrast, VE was only 13.9% for influenza-like illness (ILI) without a laboratory confirmation.