Etiology Unknown: Are Less Recognized Respiratory Pathogens Associated With a Milder Course of Illness?

Background. Multiplex assays have greatly enhanced the etiologic determination of acute respiratory infection (ARI). Yet ∼40% of ARI in the multiplex era are test-negative, suggesting that less recognized pathogens account for a significant proportion of illnesses. Evaluating the demographic and clinical characteristics of patients with unknown etiology may help refine clinical management strategies for severe ARI.

Methods. We conducted an observational study of ARI among otherwise healthy, 0- to 65-year-old individuals at five US military hospitals. Nasopharyngeal swabs were collected at enrollment and tested by a multiplex respiratory pathogen panel (Diatherix Laboratories, Inc, Huntsville, Alabama) targeting 9 viruses (rhinovirus, influenza, adenovirus, coronavirus, coxsackievirus/echovirus, RSV, parainfluenza, human metapneumovirus and bocavirus) and 10 bacteria. Demographics and risk factors were collected at baseline. Symptom severity was recorded over 10 days via patient diary.

Results. Specimens from 898 enrollees (637 adults and 261 children) were evaluated on multiplex PCR respiratory panel. Of these, 315 (35.1%) were negative for a viral pathogens and these subjects represented older, Caucasian population with low likelihood of having young children in the household. In general, both children and adults with unidentified viral etiology had milder symptoms, including less hospitalization among children (p = 0.04). However, more moderate/severe diarrhea (13.2% versus 5.9%, p < 0.01) and nausea (28.5% versus 21.5%, p = 0.04) was reported among adults with unidentified viral etiology. In addition, they were more likely to report use of antibiotics (35.6% versus 24.7%, p < 0.01) and to have abnormal chest x-rays if taken (34.4% versus 13.6%, p = 0.02) than those with known viral etiology. Adults with unidentified viral etiology had higher detection of bacterial respiratory pathogens (72.4% versus 61.1%, overall; p < 0.01), including Moraxella catarrhalis, Mycoplasma pneumoniae, and Streptococcus pyogenes.

Conclusion. ARI cases with unidentified viral etiology tended to be older and to have milder symptoms. The possible contribution of bacterial respiratory pathogens to ARI needs further evaluation and may affect management strategies for these patients.

Disclosures. L. Malone, Diatherix Laboratory: Investigator, Salary; E. Grigorenko, Diatherix laboratory: Investigator, Salary; D. Stalons, Diatherix: Employee, Salary