Case Report: Isolated Central Nervous System Melioidosis from a Non-Endemic Area.

Central nervous system (CNS) melioidosis is a rare neurological infectious disease which carries a high mortality. We describe a previously healthy middle-aged female, who presented to us with left-sided hemiparesis and was on antitubercular therapy from a previous presumed diagnosis of CNS tuberculoma. Non-characteristic imaging picture, multiple negative body fluid cultures, and positive Cerebrospinal fluid galactomannan led to a further delay in diagnosis. Gram stain of the tissue obtained from brain biopsy revealed Gram-negative rods in "safety pin" appearance. By picking up the colonies that appeared on blood agar and MacConkey agar, the identification of the clinical isolates was performed using VITEK® matrix (BioMérieux, Marcy-L'Etoile, France)-assisted laser desorption ionization time-of-flight mass spectrometry (VITEK MALDI TOF MS database version 3.2) which revealed Burkholderia pseudomallei. After the institution of appropriate treatment, she survived but with significant morbidity. A high index of suspicion should be kept for such previously healthy individuals belonging to non-endemic areas, where presentation is suspicious of an infective etiology, but not improving despite appropriate therapy. This may help in early recognition and institution of recommended treatment so that mortality can be avoided.

Melioidosis of the nervous system: atypical presentation of a rare disease in a 48-year-old man.

A 48-year-old man who worked in mining in remote, northern Australia was transferred from a rural hospital 5 days after the onset of headaches, subjective fevers and flaccid paralysis of the left upper limb. Initial investigations demonstrated inflammatory cerebrospinal fluid (CSF) changes and a longitudinally extensive cervical cord lesion. Given two serial negative blood and CSF cultures, he was treated as inflammatory myelitis with intravenous methylprednisolone. Despite the initial improvement in pain and left arm power, the patient's neurological deficit plateaued and then deteriorated with worsening neck pain, diaphragmatic dysfunction and dysphagia requiring intubation and respiratory support. A third CSF culture isolated Burkholderia pseudomallei confirming a diagnosis of neuro-melioidosis. Repeat imaging revealed the rostral extension of the original spinal cord lesion into the medulla and pons. Over the next 4 weeks, the patient's neurological deficits slowly improved with continued intravenous antibiotic therapy with meropenem and oral trimethoprim/sulfamethoxazole.

Neurological melioidosis.

Neurological abnormalities have long been recognised in animals with melioidosis, including laboratory rodents and sheep in the first Australian outbreak in 1949. Autopsies in animals have shown microabscesses and lymphocytic infiltration to be present on occasion in the same animal, but Burkholderia pseudomallei is usually able to be grown from central nervous system (CNS) tissue. In humans CNS melioidosis is unusual, but both macroscopic brain abscesses and encephalitis occur. There has been a recently recognised syndrome of meningoencephalitis with varying involvement of brainstem, cerebellum and spinal cord. The prospective melioidosis study at Royal Darwin Hospital has documented 12 cases of CNS melioidosis over 9 years out of a total of 232 cases of melioidosis (5%). Prominent features on presentation were unilateral limb weakness (6), predominant cerebellar signs (2), mixed cerebellar and brainstem features with peripheral weakness (2) and flaccid paraparesis (2). Eight patients had unilateral VIIth nerve palsy and six bulbar palsy, with five requiring prolonged ventilation. Brain CT scans are usually normal initially, but MRI shows dramatic changes. Three patients died and only three made a full recovery. In two patients with predominant mononuclear CSF pleocytosis, B. pseudomallei was cultured from CSF and autopsy in one of these showed necrotising encephalitis with microabscesses. Although it has been postulated that a neurotropic exotoxin may account for melioidosis encephalomyelitis, the recent findings and comparison with the animal data suggest that direct organism spread within the CNS may be primarily responsible. Preliminary molecular typing of isolates shows no evidence of a specific strain of B. pseudomallei responsible for CNS melioidosis end further studies are required to determine if the apparent higher rate of CNS disease in Australia is due to true regional differences or is from increased ascertainment.

Naturally occurring melioidosis in a colonized rhesus monkey (Macaca mulatta).

An aged wild-caught male rhesus monkey (Macaca mulatta), maintained in a research facility for 10 years, developed bilateral pelvic limb paralysis without other signs of disease. Unresponsive to therapy, the monkey was killed and necropsied. Chronic inflammation with osteolysis of thoracic vertebrae 10-13 was observed. Pseudomonas pseudomallei was cultured and identified from cerebrospinal fluid obtained at the site of the thoracic lesion. This Gram-negative bacterium can cause infection in animals and man and may remain latent for years before the appearance of clinical signs.