Abstract
INTRODUCTION: Herpesvirus infections are prevalent worldwide, but most run their course asymptomatically. Clinical presentations in symptomatic cases vary widely and include febrile and mononucleosis-like syndromes. In immunocompromised patients, herpetic infection can be lethal and routine laboratory tests are of little use. Use of novel techniques may provide important improvements in diagnosis and treatment of these patients. OBJECTIVE: Investigate association between different herpesviruses and the etiology of mononucleosis and febrile syndromes in Cuban immunocompetent and immunocompromised patients. METHODS: The study used multiplex nested polymerase chain reaction, enabling simultaneous detection of six herpesviruses-cytomegalovirus, herpes simplex (1 and 2), Epstein-Barr, varicella-zoster and human herpesvirus 6-to study 1157 samples (770 urine and 387 serum samples) from 1140 patients with mononucleosis-like syndrome or febrile syndrome, classified according to history of immunosuppressive disease. Samples were analyzed at the Laboratory for Sexually Transmitted Diseases (Virology) of the Pedro Kouri Tropical Medicine Institute from January 2006 through December 2009. SPSS statistical package was used and incidence rates calculated. RESULTS: Of samples studied, 20.1% were positive for some herpesvirus. Higher risk of developing active herpesvirus infections was detected in samples from immunocompromised patients with febrile syndrome compared to those of immunocompetent ones (OR 2.02, CI 1.20-3.42, p=0.007). Cytomegalovirus was the most frequently found herpesvirus in both mononucleosis-like syndrome (60.4%) and febrile syndrome (63.6%) and in both children (69.2%) and adults (55.2%), followed by Epstein-Barr virus. Cytomegalovirus was detected in 68.9% of positive urine samples and in just 47.2% of serum samples. CONCLUSIONS: This is the first Cuban study demonstrating the pathogenic role of herpesviruses, particularly cytomegalovirus, in patients with febrile or mononucleosis-like syndrome, in both immunocompetent and immunocompromised patients. Results highlight the importance of including molecular diagnosis of the herpesvirus family in investigating mononucleosis and febrile syndromes of unknown etiology and demonstrate that etiologic diagnosis would not have been feasible in many cases without the use of this diagnostic tool.
Highlights
Herpesvirus infections are prevalent worldwide, but most run their course asymptomatically
Higher risk of developing active herpesvirus infections was detected in samples from immunocompromised patients with febrile syndrome compared to those of immunocompetent ones
This is the ¿rst Cuban study demonstrating the pathogenic role of herpesviruses, cytomegalovirus, in patients with febrile or mononucleosis-like syndrome, in both immunocompetent and immunocompromised patients
Summary
Herpesvirus infections are prevalent worldwide, but most run their course asymptomatically. Clinical presentations in symptomatic cases vary widely and include febrile and mononucleosis-like syndromes. The most important biologic characteristic of these viruses is their capacity to establish lifelong latency after primary infection, with variable reactivation periods.[1]. Primary as well as reactivations or reinfections, run their course asymptomatically.[2,3,4] The clinical spectrum varies widely, from acute, benign or self-limited diseases to more severe forms, in immunosuppressed patients in which infection can lead to major complications or death.[2,3,4,5] Of particular importance among these are febrile syndrome (FS) and mononucleosis-like syndrome (MLS), organ rejection accompanied by fever in transplant recipients, encephalitis, EBV-associated lymphomas, and congenital CMV disease. Herpesviruses are considered typically opportunistic pathogens.[6,7]
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