Acute Respiratory Infections

Acute respiratory infections (ARI) are the most common infectious disease syndromes of humans. Among military personnel, the risk and burden of ARI is particularly high. Because of the tremendous impact of ARI outbreaks on training cycles and troop readiness, availability and access to effective treatment and prevention strategies in military populations is critical. Military personnel are routinely immunized for influenza and adenovirus; however, the majority of cases of ARI are caused by pathogens for which licensed vaccines do not currently exist. Moreover, data regarding the epidemiology, immunology and clinical characteristics of common respiratory pathogens, particularly those causing severe disease, are limited.

Research Area Description 

Acute respiratory infections (ARI) remain a Military Health System research priority with seasonal outbreaks posing a substantial threat to operational unit readiness as ARIs contribute approximately 30% of infectious disease hospitalizations among active-duty service members.

Although the number of ARI cases among active-duty personnel declined in 2016, in part due to the reintroduction of the adenovirus vaccination program for recruits, ~225,000 individuals were still affected with ~360,000 medical visits being attributed to ARI.  In general, military personnel are at an increased risk for ARI due to stressful working conditions and crowded training/deployment environments where respiratory infections are endemic. 

During the past year, the ARI Research Area launched several new initiatives, including an anonymous survey related to healthcare seeking behavior among military trainees with influenza-like illness (ILI) and the Study to Address Threats of ARI in Congregate Military Populations (ATARI).  The purpose of the ATARI pilot study, led by CAPT Timothy Burgess and Dr. Christian Coles, is to assess ILI transmission, etiology, and epidemiology among U.S. Army recruits at Fort Benning.  Data collection was completed in March with ~13% of enrolled recruits developing an ILI requiring medical attention.  Analysis of the data is underway. 

The centerpiece protocol of the research area is the ARI Consortium Natural History Study (ARIC NHS), which is a multisite, longitudinal observational study led by CAPT Burgess and designed to gather data on etiology, epidemiology, and immunology of ILI and severe ARI (SARI) in military populations.  Presently, it has enrolled nearly 1730 ILI cases and 155 SARI cases since initiation in 2009.  In 2017, data on ARI epidemiology, etiology, and burden from ARIC NHS were summarized in monthly surveillance reports disseminated to Armed Forces Health Surveillance Branch, Global Emerging Infections Surveillance and Response (GEIS), and Naval Health Research Center.

The IDCRP is also participating in the NIAID-sponsored, multi-site, FluPlasma 2 trial, which is designed to evaluate the efficacy of hyperimmune anti-influenza plasma for treatment of severe influenza. Nationally, there are 40 participating medical centers, including five ARIC NHS sites. The IDCRP’s effort, which is being led by CDR Janine Danko at Walter Reed National Military Medical Center, is in its second season and is expected to completed in 2018.  Through collaboration with USU, studies using novel diagnostic platforms for determining ARI etiology are also being conducted.  One such analysis is a two-year study to optimize Next Generation Sequencing for pathogen detection using respiratory samples from the ARIC NHS study, which recently identified a class of viruses not typically associated with respiratory infections.  Another new initiative is the Flu Breath Test (FBT) study, which is led by Col Patrick Danaher at Fort Sam Houston.  The goal of this research is to assess the use of exhaled volatile organic compounds for influenza diagnosis.   Enrollment for this study exceeded expectations with 49 patients enrolled in the first four months after its initiation.

In the upcoming year, the ARI Research Area will build on its infrastructure to expand data collection and analysis, particularly with SARI. We will also continue to partner with the GEIS program to conduct ILI surveillance in the high-risk trainee population at Fort Sam Houston and a follow-up survey will be carried out to identify barriers to healthcare seeking in trainees with ILI.  Based on findings from the ATARI study, a follow-up cohort study utilizing a larger trainee population will be developed, which will provide an opportunity to assess and validate novel infection biomarkers and evaluate the effectiveness repeated annual influenza vaccinations.  

Key Studies

IDCRP-045: The Acute Respiratory Infection Consortium – A multi-center military consortium for clinical research into the natural history, host response, and potential therapy of acute respiratory infection in military members and their families (ARIC NHS) The Acute Respiratory Infection Consortium (ARIC), established in 2009, is now actively engaged in the analysis of clinical and laboratory data from the ARIC Natural History Study. Numerous manuscripts are in development, with the major objectives to describe the epidemiology and clinical characteristics of influenza-like illness, to evaluate the sensitivity and specificity of new multiplex diagnostic panels, and to assess the impact of antiviral treatment, as well as vaccination, on the clinical course and outcome of influenza infection. The team is in the final stage of development of a standardized symptom severity scale for influenza. Finally, the ARI research area continues its participation in a NIAID-sponsored, multi-center randomized controlled trial of hyperimmune plasma for the treatment of severe influenza.

IDCRP-045-01: Severity symptom grading scale for influenza infection (Flu-PRO) IDCRP-046: Pilot study for collection of anti-influenza A H1N1 (Swine flu) hyper-immune plasma IDCRP-058: Clinical characteristics of novel H1N1 influenza infection in US-based military treatment facilities: A one-year retrospective review IDCRP-062: A randomized, open-label, phase 2, multicenter safety and exploratory efficacy study of investigational anti-influenza A immune plasma for the treatment of influenza

IDCRP-070: Self-administered nasal influenza vaccine: immunogenicity and feasibility of group administration

IDCRP-081: Evaluation of Psychometric Testing Properties of Severity Symptom Grading Scale of Influenza Infection: Flu-Pro Stage III

Military Impact

A greater understanding of the burden and risk factors associated with ARI in military populations is needed to inform the development of effective ARI control strategies to limit the impact of respiratory infections on the health, performance, and mission-readiness of active-duty personnel. Since 2009, findings from the ARI Research Area have advanced understanding of the changing distribution and determinants of ARI in this population. This is achieved through continued military hospital-based surveillance of respiratory infections to provide epidemiology, clinical severity, and burden of disease estimates; surveillance for viral respiratory pathogens with pandemic potential and “routine” respiratory pathogens that might impact operational readiness; contributing operational burden data to allow comparison of the cost-effectiveness of different control measures designed to enhance Force Health Protection; providing performance data on detection tools needed to assess impact on routine surveillance for pathogen-specific respiratory infections; and linking clinical syndromes and ILI/SARI etiology to facilitate pathogen-focused monitoring and diagnosis.

Highlights / Key Findings

  • Through use of cross-training with FluPlasma and ARIC NHS, operational efficiency increased, resulting in substantial cost savings
  • Number of severe acute respiratory infection cases (35) enrolled in 2017 was more than double the average number of cases enrolled annually between 2009 and 2015
  • Pilot recruit cohort study (ATARI) study completed with results demonstrating a high frequency of viruses circulating during the first two weeks of training; symptomatic ILI was associated with coronavirus, enterovirus, rhinovirus, and influenza.
  • Anonymous survey of healthcare seeking behavior in military trainees found that only 36% of trainees with ILI symptoms sought healthcare with the proportion remaining stable regardless of season; functional impact is currently being assessed
  • Infants with vitamin D deficiency had more severe viral respiratory illnesses, requiring increased duration of hospitalization (1.4 days longer than infants with sufficient vitamin D) and oxygen use (2.2 days longer) 

Partners and Collaborators

IDCRP collaborates with the National Institute of Allergy and Infectious Diseases (NIAID), Walter Reed Army Institute of Research (WRAIR), Naval Medical Research Center (NMRC), the Armed Forces Health Surveillance Branch (AFHSB) Global Emerging Infections Surveillance and Response System (GEIS) and partner military treatment facilities inside and outside the continental United States.

Publications 2017

Fairchok M, Schofield C, Chen WJ, et al. Inverse Correlation between 25-OH Vitamin D levels and severity of viral respiratory illness in infants. Journal of Infectious Disease and Epidemiology. 2017; 2(1): 1-7

Beigel JH, Tebas P, Elie-Turenne MC, et al. Immune Plasma for the Treatment of Severe Influenza: An Open-label, Multicentre, Phase 2 Randomised Study. Lancet Respiratory Medicine. 2017;5(6):500-511.

Presentations 2017 

ID Week 2016, October 26-30, New Orleans, LA:

  1. Poster # 238: Chen WJ, Arnold J, Fairchok MP, et al. Comparative Evaluation of Diatherex TEM-PCR and Biofire Film Arrau in the Detection of Viral and Bacterial Respiratory Infection.
  2. Poster # 1271: Deiss R, Chen WJ, Coles, et al. Differences in Self-Reported Severity of Symptoms Between Women and Men Experiencing Influenza-like Illness.  
  3. Poster #1273: Fairchok MP, Chen WJ, Schofield C, et al. Antibiotic Prescription Related to Influenza-like Infection.
  4. Poster #2202:  Flores MS, Sun P, Fairchok MP, et al. Cytokine Analysis and Correlation to Viral Loads in a Other-wise Healthy Population with Influenza Infection.

ISPOR 2017, May 20-24, Boston, MA

Poster PIN51: Powers J, Bacci E, Leidy NK, et al. Evaluation of the Performance Properties of the Influenza Patient-Reported Outcomes Instrument (FluPRO) in Patients with Influenza-like Illness (ILI).

MHSRS 2017, August 27-30, Kissimee, FL:

Oral Presentation: Coles CL, Chen WJ, Milzman JO,  et al. Study to Address Threats of Acute Respiratory Infections among Congregate Military Populations (ATARI).

ID Week 2017, October 4-8, 2017, San Diego, CA

  1. Poster #647:  Lewnard J, Chen WJ, Milzman JO, et al. Transmission dynamics of respiratory viruses in a congregated military population: prospective cohort study.
  2. Poster #661:  Chen WJ, Milzman JO, Danahar P, et al. Burden of Influenza-like Illness among military personnel receiving advanced training at Ft. Sam Houston, TX.
  3. Poster #1027: Coles C, Chen WJ, Milzman JO, et al. Study to Address Threats of Acute Respiratory Infections among Congregate Military Populations (ATARI).
  4. Poster #1048: Fairchok M, Chen WJ, Mor D,  et al. Clinical Characteristics of Parainfluenza Virus Infection among Healthy Subjects with Influenza-like Illness.
  5. Poster #1460: Lee R, Won S, Hansen C, et al. Are Higher Vitamin D Levels Associated with Improved Influenza Vaccine Immunogenicity and Fewer Healthcare Encounters for Respiratory Infections among Young Adults?
  6. Poster #1996: Schofield C, Chen WJ, Fairchok M, et al. Epidemiologic Risk, Influenza Subtype, Clinical Severity and Viral Shedding as a Function of Baseline Influenza A Viral Load.
  7. Poster #2001: Maves R, Chen WJ, Fairchock, et al. Etiology and Clinical Characteristics of Influenza-like Illness in Healthy Adults by Hospitalization Status.

Publications 2015

Chen WJ, Arnold JC, Fairchok MP, et al. Epidemiologic, clinical, and virologic characteristics of human rhinovirus infection among otherwise healthy children and adults: Rhinovirus among adults and children. Journal of Clinical Virology. 2015;64(3):74-82.

Fairchok MP, Chen WJ, Arnold JC, et al. Neuraminidase inhibitor therapy in a military population. Journal of Clinical Virology. 2015;67:17-22.


Sanchez JL, Cooper MJ, Myers CA, Cummings JF, Vest KG, Russell KL, Sanchez JL, Hiser MJ, Gaydos CA. 17 June 2015. Respiratory infections in the U.S. military: recent experience and control. Clin Microbiol Rev.