Influenza-like illness surveillance on the California-Mexico border, 2004-2009.

BACKGROUND: Since 2004, the Naval Health Research Center, with San Diego and Imperial counties, has collaborated with the US Centers for Disease Control and Prevention to conduct respiratory disease surveillance in the US-Mexico border region. In 2007, the Secretariat of Health, Mexico and the Institute of Public Health of Baja California joined the collaboration. OBJECTIVES: The identification of circulating respiratory pathogens in respiratory specimens from patients with influenza-like illness (ILI). METHODS: Demographic, symptom information and respiratory swabs were collected from enrollees who met the case definition for ILI. Specimens underwent PCR testing and culture in virology and bacteriology. RESULTS: From 2004 through 2009, 1855 persons were sampled. Overall, 36% of the participants had a pathogen identified. The most frequent pathogen was influenza (25%), with those aged 6-15 years the most frequently affected. In April 2009, a young female participant from Imperial County, California, was among the first documented cases of 2009 H1N1. Additional pathogens included influenza B, adenovirus, parainfluenza virus, respiratory syncytial virus, enterovirus, herpes simplex virus, Streptococcus pneumoniae, and Streptococcus pyogenes. CONCLUSIONS: The US-Mexico border is one of the busiest in the world, with a large number of daily crossings. Due to its traffic, this area is an ideal location for surveillance sites. We identified a pathogen in 36% of the specimens tested, with influenza A the most common pathogen. A number of other viral and bacterial respiratory pathogens were identified. An understanding of the incidence of respiratory pathogens in border populations is useful for development of regional vaccination and disease prevention responses.

Evaluation of PCR testing of ethanol-fixed nasal swab specimens as an augmented surveillance strategy for influenza virus and adenovirus identification.

Viral culture isolation has been widely accepted as the "gold standard" for laboratory confirmation of viral infection; however, it requires ultralow temperature specimen storage. Storage of specimens in ethanol at room temperature could expand our ability to conduct active surveillance and retrospective screenings of viruses with rapid and inexpensive real-time PCR tests, including isolates from remote regions where freezing specimens for culture is not feasible. Molecular methods allow for rapid identification of viral pathogens without the need to maintain viability. We hypothesized that ethanol, while inactivating viruses, can preserve DNA and RNA for PCR-based methods. To evaluate the use of ethanol-stored specimens for augmenting surveillance for detection of influenza viruses A and B and adenoviruses (AdV), paired nasal swab specimens were collected from 384 recruits with febrile respiratory illness at Fort Jackson, S.C., in a 2-year study. One swab was stored at ambient temperature in 100% ethanol for up to 6 months, and the other swab was stored at -70 degrees C in viral medium. For viral detection, frozen specimens were cultured for a variety of respiratory viruses, and ethanol-fixed specimens were tested with TaqMan (TM) probe and LightCycler SYBR green (SG) melting curve assays with at least two different PCR targets for each virus. The sensitivities of the TM and SG assays on specimens stored in ethanol for 1 month were 75% and 58% for influenza A, 89% and 67% for influenza B, and 93 to 98% and 57% for AdV, respectively. Lower specificities of the real-time assays corresponded to the increased detection of PCR-positive but culture-negative specimens. Influenza virus RNA was detected as well or better after 6 months of storage in ethanol.

National Department of Defense Surveillance for Invasive Streptococcus pneumoniae: antibiotic resistance, serotype distribution, and arbitrarily primed polymerase chain reaction analyses.

To provide surveillance among US military personnel and their beneficiaries, 157 invasive Streptococcus pneumoniae clinical isolates were collected systematically from 7 large military hospitals between August 1997 and August 1999. The isolates were studied for antibiotic resistance, and 120 were serotyped and subjected to arbitrarily primed polymerase chain reaction (AP-PCR). Fifty (31.9%) of 157 isolates had intermediate or high-level resistance to penicillin, and 15.9% had multidrug resistance. The most common serotypes were 4, 6B, 9V, 14, 19F, and 23F. Those serotypes associated with penicillin resistance were 6B, 9V, 19A, and 19F. Most invasive disease cases were caused by serotypes included in the currently available 23- and 7-valent pneumococcal vaccines. By use of AP-PCR, 4 DNA groups were correlated with health care site (P< or =.0001). These results are valuable in assessing appropriate use of antibiotics and vaccines against S. pneumoniae in both military personnel and their families.

Adult adenovirus infections: loss of orphaned vaccines precipitates military respiratory disease epidemics. For the Adenovirus Surveillance Group.

Adenovirus vaccines have greatly reduced military respiratory disease morbidity since the 1970s. However, in 1995, for economic reasons, the sole manufacturer of these vaccines ceased production. A population-based adenovirus surveillance was established among trainees with acute respiratory illness at 4 US military training centers as the last stores of vaccines were depleted. From October 1996 to June 1998, 1814 (53.1%) of 3413 throat cultures for symptomatic trainees (78% men) yielded adenovirus. Adenovirus types 4, 7, 3, and 21 accounted for 57%, 25%, 9%, and 7% of the isolates, respectively. Unvaccinated trainees were much more likely than vaccinated trainees to be positive for types 4 or 7 (odds ratio [OR] = 28.1; 95% CI, 20.2-39.2). Two training centers experienced epidemics of respiratory disease affecting thousands of trainees when vaccines were not available. Until a new manufacturer is identified, the loss of orphaned adenovirus vaccines will result in thousands of additional preventable adenovirus infections.

Factor analysis of self-reported symptoms: does it identify a Gulf War syndrome?

Active duty US Naval mobile construction battalion personnel (Seabees) were surveyed in 1994 for the presence of a variety of symptoms. Questions were drawn from the Hopkins Symptom Checklist and from a collection of symptoms either defining clinical depression or commonly reported by Persian Gulf War veterans. Of those surveyed, 524 were Gulf War veterans and 935 were nondeployed Gulf War-era veterans. Factor analysis applied to Gulf War veterans yielded five factors, three deriving from the Hopkins Symptom Checklist, one suggesting clinical depression, and one containing symptoms commonly reported by Gulf War veterans. Factor analysis applied to nondeployed veterans yielded five similar factors. Three of the factors yielded statistically significantly greater standardized factor scores for Gulf War veterans than for nondeployed veterans. Four of the factors resembled factors resulting from a previous analysis on a sample of similar Gulf War veterans. Gulf War veterans and nondeployed era veterans reported similar clusters of symptoms and illnesses. However, Gulf War veterans reported these same clusters with greater frequencies than did nondeployed veterans. The authors conclude that, in contrast to a previous report, factor analysis did not identify a unique Gulf War syndrome.

Respiratory diseases among U.S. military personnel: countering emerging threats.

Emerging respiratory disease agents, increased antibiotic resistance, and the loss of effective vaccines threaten to increase the incidence of respiratory disease in military personnel. We examine six respiratory pathogens (adenoviruses, influenza viruses, Streptococcus pneumoniae, Streptococcus pyogenes, Mycoplasma pneumoniae, and Bordetella pertussis) and review the impact of the diseases they cause, past efforts to control these diseases in U.S. military personnel, as well as current treatment and surveillance strategies, limitations in diagnostic testing, and vaccine needs.

No serologic evidence of an association found between Gulf War service and Mycoplasma fermentans infection.

Occult occupational infection with Mycoplasma fermentans has been proposed as a cause for illness among Persian Gulf War veterans. Symptom data and sera from a 1994-1995 cross-sectional survey of Navy Seabees were used to select symptomatic and asymptomatic Gulf War veterans and nondeployed veterans to evaluate this hypothesis. Survey sera from 96 Seabees were matched to prewar (before September 1990) archived sera. Immunoblot serologic analyses were performed for M. fermentans in a controlled, blinded fashion. Both Gulf War veterans and nondeployed veterans had prewar and postwar serologic evidence of M. fermentans infection consistent with natural infection data. Among study subjects collectively, and stratified by Gulf War service, none of the immunoblot banding profiles (prewar or postwar) or their changes over time were associated with postwar symptoms. These serologic data do not support the hypothesis that Gulf War veterans have experienced Gulf War-related morbidity from M. fermentans infection.

Increased postwar symptoms and psychological morbidity among U.S. Navy Gulf War veterans.

To investigate reports on war-related morbidity, 527 active-duty Gulf War veterans and 970 nondeployed veterans from 14 Seabee commands were studied in 1994 with a questionnaire, sera collection, handgrip strength, and pulmonary function testing. The questionnaire assessed postwar symptoms, war exposures, and screened for chronic fatigue syndrome, post-traumatic stress disorder, and psychological symptoms suggesting neurosis (Hopkins Symptom Checklist). Sera were tested with four nonspecific reactant assays: C-reactive protein, transferrin, ferritin, and haptoglobin. Gulf War veterans reported a higher prevalence for 35 of 41 symptoms, scored higher on psychological symptom scales, were more likely to screen for post-traumatic stress disorder, had lower handgrip strength, and had higher serum ferritin assay results. Numerous comparisons of these morbidity outcomes with 30 self-reported exposures demonstrated many associations, but no unique exposure or group of exposures were implicated. Morbidity data are consistent with other postwar observations, but the etiology for morbidity findings remains uncertain.

Gulf War Veterans' Health Registries. Who is most likely to seek evaluation?

Since the Persian Gulf War ended in 1991, many veterans have sought medical evaluation in the Department of Veterans Affairs Persian Gulf Veterans' Health Registry (VA registry) or the Department of Defense's Comprehensive Clinical Evaluation Program (DoD registry). Using combined data collected from 1993 to 1997 from the VA and DoD registries, the authors compared the characteristics of registry participants (n=74,653) with those of all Gulf War veterans (n=696,531) to determine the personnel most likely to seek medical evaluation. Using multiple logistic regression, the authors found that service branch and type were strongly associated with registry participation, with Army (adjusted odds ratio (OR)=4.7, 95% confidence interval (CI) 4.6-4.9) and National Guard (OR=2.6, 95% CI 2.5-2.6) personnel at highest odds compared with reference category personnel. Registry participants also were more likely to have been stationed in the Gulf War theater during the fighting (OR=2.2), to be older (>31 years/<22 years OR=2.1), to have been an enlisted person (OR=2.0), to have been construction workers (OR=1.3), to be female (OR=1.3), and to have been hospitalized during the 12-month period before the war (OR=1.2). These findings are useful in generating hypotheses regarding postwar morbidity. They also suggest that subpopulations of Gulf War veterans have a higher prevalence of symptoms and merit further study.

Immune response to moxalactam in rabbits and in humans.

Three of 23 New Zealand white rabbits immunized with moxalactam or bovine serum albumin (BSA)-moxalactam conjugates produced specific antimoxalactam antibodies. Rabbits that produced antimoxalactam had been immunized, by a novel approach, with heat-aggregated BSA-moxalactam conjugates containing Corynebacterium parvum as adjuvant. Use of liposomes to augment antibody response in the rabbits was successful for the production of anti-BSA antibodies, but failed to result in production of antimoxalactam. One antimoxalactam was chosen for further study, was specifically inhibited with moxalactam (10(-5) mol/L), and did not cross-react with any of the 11 other cephalosporins or eight penicillins tested (in concentrations of 10(-2) mol/L). In addition, the antibody did not demonstrate any carrier specificity. One of eight humans receiving intravenous moxalactam therapy developed a low titer, low avidity antimoxalactam. This patient was a "good responder," inasmuch as he also produced three transfusion-stimulated alloantibodies to red cell antigens during the study. Although the patient developed the antimoxalactam antibody while the drug was being administered, there was no evident adverse clinical reaction. This is the first report of antimoxalactam produced either in experimental animals or in humans. Our data indicate that moxalactam may be a relatively poor immunogen in rabbits requiring special immunization protocols. The one antibody studied does not cross-react with other structurally related antibiotics. Although human antimoxalactam may be produced, no adverse effects were detected in the one case observed.