Elsevier

The Lancet

Volume 362, Issue 9395, 8 November 2003, Pages 1536-1541
The Lancet

Articles
Herpes simplex virus in the respiratory tract of critical care patients: a prospective study

https://doi.org/10.1016/S0140-6736(03)14740-XGet rights and content

Summary

Background

Herpes simplex virus (HSV) is occasionally detected in the lower respiratory tract of patients in intensive care, but its clinical importance in such situations remains unclear. We did a prospective cohort study to define the prevalence, origin, risk factors, and clinical relevance of HSV in the respiratory tract of patients undergoing critical care.

Methods

We tested 764 patients admitted to intensive care for the presence of HSV in the respiratory tract, and assessed statistical relations between this virus and clinical variables.

Findings

HSV was detected by oropharyngeal swab in the upper respiratory tract of 169 (22%) of 764 patients, within 10 days of admission for 150 (89%) of these individuals. The virus was isolated in 58 (16%) of 361 patients whose lower respiratory tract was sampled. The presence of HSV in the throat was a risk factor for development of HSV infections in the lower respiratory tract (p < 0·001). HSV was isolated most frequently in patients with severe disease. HSV in the throat was associated with acute respiratory distress syndrome (p < 0·001) and with increased length of stay in intensive care (p < 0·001).

Interpretation

Our data suggest that HSV reactivation or infection of the upper respiratory tract is frequent among patients in intensive care, and is a risk factor for development of lower respiratory tract infection with this virus, possibly by means of aspiration.

Introduction

Primary infection with herpes simplex virus type 1 (HSV1) can either be asymptomatic or result in various clinical syndromes involving mucocutaneous surfaces, the central nervous system, and, very occasionally, visceral organs.1, 2 After this primary infection, which usually occurs during childhood, the virus may remain latent in a nonreplicating form in neurones of dorsal root ganglia, ganglia of the autonomic nervous system, or both.3 We do not know how latency is established, or whether some HSV strains reactivate more frequently than others. Local stimuli (eg, ultraviolet light and tissue damage) as well as systemic stimuli can cause reactivation of the virus and potentially clinical disease. Systemic stimuli include fever due to bacterial or viral infection, menstruation, surgery, physical or emotional stress, and hormonal imbalance.4, 5 Immunocompromised people, especially organ transplant recipients, are at increased risk of widespread and devastating infection of the gastrointestinal or respiratory tract.6 In adults, HSV infection of the lower respiratory tract is very rare, and has been recorded almost exclusively in combination with severe immunosuppression.6 HSV has been visualised by immunohistochemistry in lung tissue from burn patients dying with acute lung injury,7 and occasionally in lower respiratory tract samples from surgical patients in intensive care units (ICUs).8 However, the frequency of HSV infections of the lower respiratory tract in ICU patients and the clinical importance of such infections remain unknown. In a retrospective study done in our hospital from 1992 to 1997, such infections were frequently detected, but their clinical importance could not be clarified. We therefore undertook a prospective study to define the prevalence of respiratory tract HSV reactivation and infection in patients admitted to our ICU, to identify risk factors and the possible origin and clinical relevance of the virus.

Section snippets

Study population

During a 20-month period (Nov 15, 1999, to June 15, 2001), all adults (aged ≥ 18 years) admitted for at least 3 days in the Intensive Care Unit (ICU) of the University Hospital of Antwerp were included in a prospective study. The University Hospital of Antwerp is a 600-bed tertiary care hospital with a 30-bed ICU. The number of admissions in this unit is approximately 1600 per year, including surgical, medical, and trauma patients. The study protocol was approved by the institutional review

Results

HSV was detected in the throats of two (2%) healthy volunteers and three (3%) patients not admitted to the ICU. The healthy volunteers were younger than the control patients and the ICU patients, and fewer were male (data not shown). During the study, oropharyngeal swabs were obtained from 764 ICU patients, of whom 169 (22%) had at least one swab positive for HSV (figure 1). Lower respiratory tract specimens were obtained from 361 (47%) of these 764 patients. HSV was detected in lower

Discussion

We have shown that the frequency of HSV in the upper respiratory tract of ICU patients, as assessed by a weekly oropharyngeal swab, can be high as 22%. Our findings, and those of other investigations, show that HSV is present in the throat of 2–3% of adults in the general population.16 Several stimuli are known to cause reactivation, although the exact mechanism remains unknown. The mucosal damage associated with intubation and mechanical ventilation could reactivate latent HSV in the regional

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