Testicular involvement during Toscana virus infection: an unusual manifestation?

Abstract

Toscana virus (TOSV), transmitted by the Phlebotomus genera, is the most common cause of viral meningitis in the Mediterranean area during summer [1]. Generally, the disease is benign and self-limited, although severe complications such as encephalitis and cerebral ischemia are described [2]. Asymptomatic infections and clinical manifestations in the absence of central nervous system involvement are also documented [3, 4]. We describe an unusual manifestation of TOSV infection in a patient residing in central Italy (Siena district, Tuscany). On 4 September 2012, a 29-year-old previously healthy man was admitted to hospital for fever and severe headache lasting 3 days; testicular pain and diarrhea were also reported. On admission, the patient was suffering and alert with an axillary temperature of 37.3 C, pulse rate of 80 beats/min, respiratory rate of 20 breaths/min, and blood pressure of 110/80 mmHg. Physical examination revealed signs of meningeal irritation, in the absence of focal neurological deficits, tenuous maculopapular rash in the trunk and upper limbs, pharyngeal hyperemia, and swelling and tenderness of the right testicle with no other genital abnormalities. The laboratory tests showed a C-reactive protein level of 1.78 mg/dL (normal value \0.5), white blood cell (WBC) count 11,200/mm (neutrophils 70.4 %), aspartate aminotransferase (AST) 24 U/l, alanine aminotransferase (ALT) 44 U/l, and IgG 582 mg/dL. The erythrocyte sedimentation rate, hemoglobin, platelet count, procalcitonin, renal function, amylase, electrolytes, lactate dehydrogenase, creatine phosphokinase, C3, C4, IgA, IgM, and bilirubin were all within the normal limits. Computed tomography (CT) scan of the brain without contrast medium, chest X-ray, and electrocardiography (ECG) were negative. The testicular ultrasound showed minimal right hydrocele. Cerebrospinal fluid (CSF) examination revealed normal glucose level, increased protein levels (161 mg/dL), and pleocytosis (1,745 cells/mm, 61.7 % lymphocytes). The patient was treated with an empirical therapy based on ceftriaxone and intravenous acyclovir. TOSV was detected by specific nested reverse transcription polymerase chain reaction (RT-PCR) in CSF, while bacterial and fungal cultures, as well as results of PCR for picornavirus, HSV-1 and HSV-2, and Mycobacterium tuberculosis were negative in the same specimen. Blood cultures were negative and serology against TOSV showed positivity for IgM and IgG; antibodies against mumps virus were compatible with past infection. The patient gradually improved, with rapid disappearance of the rash and testicular pain; after 7 days, he was discharged in good condition. This case underlines that, in addition to the typical neurological manifestations, TOSV infection may involve other organs [1]. Although cutaneous rash has been reported several times, testicular involvement, as in the patient described here, has only been documented in a single previous report [3]. From a pathogenetic point of view, the concomitance and the rapid disappearance of genital symptoms during the infection seem to suggest, in the absence of other obvious causes, a direct relationship with viral replication.