Clinical Presentations for Influenza and Influenza-Like Illness in Young, Immunized Soldiers

Military Medicine, Jan 2005 by McNeill, K Mills, Vaughn, Beverly L, Brundage, Mary B, Li, Yuanzhang, Et al

Concern about respiratory diseases in soldiers increased in the late 1990s as production of the successful adenovirus vaccines stopped and the possibilities of an emergent pandemic influenza strain and use of bioweapons by terrorists were seriously considered. Current information on the causes and severity of influenza-like illness (ILI) was lacking. Viral agents and clinical presentations were described in a population of soldiers highly immunized for influenza. Using standard virus isolation techniques, 10 agents were identified in 164 (48.2%) of 340 soldiers hospitalized for ILL Influenza isolates (29) and adenoviruses (98) occurred most frequently. Most influenza cases were caused by influenza A and probably resulted from a mismatch between circulating and vaccine viruses. Most (58.5%) patients with an adenovirus had a chest radiograph; 31.3% of these had an infiltrate. Clinical findings did not differentiate ILI caused by the various agents. Only 29 cases of influenza occurred in ~7,200 person-years of observation, supporting the use of influenza vaccine.

Introduction

During the period from 1994 to 1999, three events increased interest in the causes and severity of influenza-like illness (ILI) in soldiers and the ability of providers in the military health system to identify the agent or agents causing acute respiratory diseases. The first event was the loss of two important vaccines. Beginning in 1971, the primary causes of acute respiratory disease in military basic trainees, adenovirus types 4 and 7, were controlled by oral enteric-coated vaccines.1 In 1994, the sole manufacturer of the vaccines announced that vaccine production would be terminated permanently.2 In response, the military services limited administration of the existing vaccine supply to the higher-risk colder months, with the depletion of all vaccine stocks occurring in 1999.2 Some medical leaders called for quickly awarding a contract to reestablish production of the vaccines. Others argued that adenovirus-associated acute respiratory disease in previously healthy soldiers was a mild disease that did not warrant an expensive, multiyear vaccine initiative. The second event was more of a growing concern that terrorists would use as bioweapons respiratory pathogens such as Bacillus anthracis. This fueled discussions on the range of respiratory pathogens that might occur in military populations and the ability of providers to quickly identify the agents.3 The third event was the appearance of a threatening H5N1 influenza A strain with pandemic potential in Hong Kong in 1997.4 This event highlighted the possibility that the effectiveness of the mandatory, annual military influenza immunization program could be compromised by the emergence of an influenza virus antigenically different from the viruses used to make the vaccine. Formal meetings of medical leaders in the Department of Defense (DoD) followed to address the likelihood that novel, unexpected influenza viruses would be detected in a timely fashion so that vaccine effectiveness could be determined and outbreak interventions expeditiously implemented.5

Interruption in the routine year-round administration of the adenovirus vaccines resulted in a resurgence of ILI at military training centers and prompted the initiation of enhanced laboratory-based surveillance at selected Army installations in 1997.1,2,6-8 The enhanced surveillance program was initiated to monitor changes in ILI, project increases in clinical work load, and provide epidemiological data needed to develop a contract for a new vaccine producer and to test the next generation of adenovirus vaccines.6-8 Data and information from this surveillance program also provided an opportunity to address concerns about the causes and severity of ILI in soldiers. Using data from the surveillance initiative at Fort Gordon, Georgia, we identified the viral agents causing ILI and the proportion of ILI cases for which no agent could be identified. We also determined whether the identified pathogens were associated with clinically distinguishing features and assessed the clinical severity of ILL Lastly, we defined the occurrence of clinical influenza in a highly immunized U.S. Army population.

Methods

Fort Gordon is an Army advanced training installation. Soldiers come to Fort Gordon after completing initial entry (basic) training at other military installations. The epidemiological assessment of the occurrence of acute respiratory disease at Fort Gordon during the time of this study has been reported elsewhere.7 From April 1, 1997 to March 31, 1999, we studied 340 Army trainees hospitalized with acute, febrile respiratory illness at Dwight D. Elsenhower Army Medical Center (DDEAMC) at Fort Gordon. The case definition for study enrollment was fever (≥38,1°C or ≥ 100.5°F orally) with one or more symptoms of an acute respiratory illness.7 This case definition has been used in the military to define cases of acute respiratory disease, which is also referred to as febrile respiratory illness. In this study, we refer to our patients as having ILL The approximate size of the Fort Gordon trainee population during the study period was 3,600 individuals, of which approximately 20% were women.7 The age range of our patients was 17 to 34 years (median age, 19 years); 19.7% were women. An estimated 80% of soldiers hospitalized with ILI during the study period were evaluated.7