Central Nervous System Melioidosis Research Articles

Encephalomyelitis as a rare presentation of melioidosis

Cerebral melioidosis is a rare entity which is minimally reported in literature, having multiple diagnostic challenges as it mimics most of the other diseases of the central nervous system (CNS). Spectrum of CNS melioidosis depends on the entry of the organism and immune status of the patient. Due to the delay in diagnosis, it has a high morbidity and mortality. It is thought to be a disease of the immunocompromised with risk of exposure to soil or surface water. We present a case of an immunocompetent patient without any known risk factors for significant exposure, who presented with fever and rapidly progressive multiple cranial nerve palsies followed by reduced level of consciousness and cerebellar signs. She was eventually diagnosed to have encephalomyelitis, a form of neuro melioidosis, with radiological evidence of acute demyelinating encephalomyelitis, and successfully treated with parenteral meropenem for intensive phase and cotrimoxazole for a long eradication phase. High index of suspicion and early initiation of treatment with suitable antibiotics for an optimal duration, evidenced complete recovery.

Favourable outcome in central nervous system melioidosis following plasmapheresis

Favourable outcome in central nervous system melioidosis following plasmapheresis

Type VI Secretion System Accessory Protein TagAB-5 Promotes Burkholderia pseudomallei Pathogenicity in Human Microglia.

Central nervous system (CNS) melioidosis caused by Burkholderia pseudomallei is being increasingly reported. Because of the high mortality associated with CNS melioidosis, understanding the underlying mechanism of B. pseudomallei pathogenesis in the CNS needs to be intensively investigated to develop better therapeutic strategies against this deadly disease. The type VI secretion system (T6SS) is a multiprotein machine that uses a spring-like mechanism to inject effectors into target cells to benefit the infection process. In this study, the role of the T6SS accessory protein TagAB-5 in B. pseudomallei pathogenicity was examined using the human microglial cell line HCM3, a unique resident immune cell of the CNS acting as a primary mediator of inflammation. We constructed B. pseudomallei tagAB-5 mutant and complementary strains by the markerless allele replacement method. The effects of tagAB-5 deletion on the pathogenicity of B. pseudomallei were studied by bacterial infection assays of HCM3 cells. Compared with the wild type, the tagAB-5 mutant exhibited defective pathogenic abilities in intracellular replication, multinucleated giant cell formation, and induction of cell damage. Additionally, infection by the tagAB-5 mutant elicited a decreased production of interleukin 8 (IL-8) in HCM3, suggesting that efficient pathogenicity of B. pseudomallei is required for IL-8 production in microglia. However, no significant differences in virulence in the Galleria mellonella model were observed between the tagAB-5 mutant and the wild type. Taken together, this study indicated that microglia might be an important intracellular niche for B. pseudomallei, particularly in CNS infection, and TagAB-5 confers B. pseudomallei pathogenicity in these cells.

Melioidosis of the central nervous system; impact of the bimABm allele on patient presentation and outcome.

The autotransporter protein Burkholderia intracellular motility A (BimA) facilitates the entry of Burkholderia pseudomallei into the central nervous system (CNS) in mouse models of melioidosis. Its role in the pathogenesis of human cases of CNS melioidosis is incompletely defined. Consecutive culture-confirmed cases of melioidosis at two sites in tropical Australia after 1989 were reviewed. Demographic, clinical and radiological data of the patients with CNS melioidosis were recorded. The bimA allele (bimABm or bimABp) of the B. pseudomallei isolated from each patient was determined. Of the 1587 cases diagnosed at the two sites during the study period, 52 (3.3%) had confirmed CNS melioidosis; 20 (38.5%) had a brain abscess, 18 (34.6%) had encephalomyelitis, 4 (7.7%) had isolated meningitis and 10 (19.2%) had extra-meningeal disease. Among the 52 patients, there were 8 (15.4%) deaths; 17/44 (38.6%) survivors had residual disability. The bimA allele was characterized in 47/52; 17/47 (36.2%) had the bimABm allele and 30 (63.8%) had the bimABp allele. Patients with a bimABm variant were more likely to have a predominantly neurological presentation (odds ratio (OR) (95% confidence interval (CI)): 5.60 (1.52-20.61), p=0.01), to have brainstem involvement (OR (95%CI): 7.33 (1.92-27.95), p=0.004) and to have encephalomyelitis (OR (95%CI): 4.69 (1.30-16.95), p=0.02. Patients with a bimABm variant were more likely to die or have residual disability (odds ratio (95%CI): 4.88 (1.28-18.57), p=0.01). The bimA allele of B. pseudomallei has a significant impact on the clinical presentation and outcome of patients with CNS melioidosis.

Central nervous system melioidosis: A systematic review of individual participant data of case reports and case series.

BackgroundCentral nervous system (CNS) melioidosis is rare. However, delayed diagnosis and treatment could lead to fatality. To identify knowledge of CNS melioidosis, we systematically review case reports and case series.Methodology/Principal findingsWe searched through PubMed, Web of Science and Thai-Journal Citation Index databases as well as Google Scholar with the last date on July 10, 2018. The diagnosis of CNS melioidosis had to be confirmed with culture, serology or polymerase chain reaction. We excluded the animal cases and the studies that the clinical data were not available. We identified 1170 relevant studies, while 70 studies with a total of 120 patients were analyzed. Ninety-three percent of patients were reported from the endemic area of melioidosis. Median age was 40 years (IQR 18–53), and 70% were men. A total of 60% had one or more risk factors for melioidosis. The median duration from clinical onset to diagnosis was ten days (IQR 5–25). Fever (82%), headache (54%), unilateral weakness (57%) and cranial nerve deficits (52%) are among the prominent presentation. Most patient (67%) had at least one extraneurological organ involvement. The CSF profile mostly showed mononuclear pleocytosis (64%), high protein (93%) and normal glucose (66%). The rim-enhancing pattern (78%) is the most frequent neuroimaging finding in encephalomyelitis and brain abscess patients. Both brainstem (34%) and frontal lobe (34%) are the most affected locations. Mortality rate was 20%.Conclusions/SignificanceThis study is the most extensive systematic review of case reports and case series of CNS melioidosis in all age groups. However, the results should be cautiously interpreted due to the missing data issue. The propensity of brainstem involvement which correlates with prominent cranial nerve deficits is the characteristic of CNS melioidosis especially encephalomyelitis type. The presenting features of fever and neurological deficits (especially cranial nerve palsies) along with the mononuclear CSF pleocytosis in a patient who lives in the endemic area and also has the risk factor for melioidosis should raise the CNS melioidosis as the differential diagnosis.

Multi-systemic melioidosis: a clinical, neurological, and radiological case study from Hainan Province, China

BackgroundMelioidosis is a tropical disease caused by Burkholderia pseudomallei (B. pseudomallei). It can infect any organ system and lead to multiple abscesses. A few studies reported that central nervous system (CNS) is also involved.We present a diabetic patient with multi-systemic melioidosis that affected the CNS, thorax, and spleen. The aim was to study the clinical and radiological features of melioidosis and enhance understanding of the disease.Case presentationA 38-year-old male presented with cough and expectoration mixed with blood for several days. Chest computed tomography (CT) showed a patchy opacity in his left lung, and multiple low-density lesions in his spleen. After 10 days of antibiotics treatment, his clinical symptoms improved and he was discharged from the hospital. But 8 months later, the patient experienced sudden onset of left limb weakness and seizure and was re-admitted to the hospital. Brain CT indicated a low-density lesion over the right frontal lobe, and magnetic resonance imaging (MRI) indicated a well-enhanced lobulated lesion with multiple diffusion restriction areas in the lesion. He had a neuronavigation-guided open surgery but no malignancy was found. B. pseudomallei was cultured from the operative samples. After 4 months of systemic and intraventricular antibiotic administration treatment, he recovered complete consciousness with left hemiparesis.ConclusionsMulti-systemic melioidosis may present atypical clinical, neurological, and radiological manifestations. It is extremely important to accurately diagnose before treatment is selected. CNS melioidosis in early stage manifests similar symptoms to malignancy or stroke. It might mislead to a false diagnose. Diffusion weighted imaging (DWI) can help in differentiate abscesses from cystic tumours.

Central nervous system melioidosis: Systematic review of case reports and case series

Central nervous system melioidosis: Systematic review of case reports and case series

Central nervous system melioidosis in the pediatric age group: review

Melioidosis is a potentially fatal infectious disease caused by Burkholderia pseudomallei. Neurologic involvement in pediatric age group is very rare, and only a handful of cases have been reported in literature. We sought to provide a systematic review of pediatric neurologic melioidosis. Literature review was performed to analyze reported cases of pediatric neurologic melioidosis (≤16years) by searching online database (PubMed/MEDLINE). Twenty-seven cases were analyzed. Mean age was 6.7years (range 2days-14years) and around 50% were older children (>5years). Cranial nerve palsies and fever were most common presenting features. Major manifestations were meningoencephalitis in 16 (59%) and cerebral abscesses in eight (29%) cases. Abscesses were mostly located in parietal lobe. Among older children, abscesses were common than meningeal disease, while being converse for neonates. Mean follow-up duration was 11.5months. Ten cases showed good to excellent outcome, while eight cases had fair (incomplete recovery) outcomes. The overall mortality rate was 18.5% (5/27) and tends to decrease with age. Among the five deaths, 4 (80%) had septicemia or pneumonia. Pediatric neurologic melioidosis is very rare. Meningoencephalitis is the most common presentation. Mortality is the highest in neonates. Ceftazidime appears to be the drug of choice in intensive phase, although the best drug in maintenance phase cannot be commented upon, especially in very young children.

Neuromelioidosis: Craniospinal MRI Findings in Burkholderia pseudomallei Infection.

To investigate magnetic resonance imaging (MRI) findings of central nervous system (CNS) infection with Burkholderia pseudomallei. Retrospective analysis of 10 patients (5 male and 5 female, age range from 13 to 69 years) with CNS melioidosis confirmed on culture of blood, sputum, cerebrospinal fluid, brain biopsy, and postmortem brain tissue. Clinical data were collected and MRI brain and/or spine were independently reviewed. Seven patients with brain parenchymal or intramedullary spinal cord lesions demonstrated rim-enhancing microabscesses with propensity for white matter tracts including the corticospinal tracts, corpus callosum, and cerebellar peduncles. Three of these 7 patients also showed thickening and enhancement of the trigeminal nerves with contiguous spread to brain stem trigeminal nuclei. Three patients had isolated extraaxial disease with findings including meningeal enhancement, extradural abscess, skull osteomyelitis, and scalp abscess. Spread of microabscesses along white matter tracts and frequent trigeminal nerve involvement are unique imaging characteristics of CNS melioidosis. These findings may provide insight into potential mechanisms for B. pseuodomallei entry into the CNS through direct axonal transport in cranial nerves bypassing the blood brain barrier. Prompt recognition of the neuroimaging features of this potentially fatal infection may allow for early microbiological culture and treatment.

Spectra of central nervous system melioidosis

Burkholderia pseudomallei infection of the central nervous system (CNS) is rare with less than 50 cases reported over the last 30 years. The retrospective melioidosis study at University Malaya Medical Centre has documented three cases of CNS melioidosis out of more than 160 cases of melioidosis since 1978. There were two patients with brain abscess and one with spinal epidural abscess. The predisposing factors were: one patient was an aboriginal farmer and the other two were diabetic. Their age ranged from 17 to 45 years. Prominent neurological features were limb weakness, cranial nerve palsy (6th and 7th) and visual disturbance. CT brain scan and MRI spine showed abscess formation, subdural collection, and spinal epidural collection, osteomyelitis of vertebra and occipital bone and also sagital sinus thrombosis. All these patients underwent surgical drainage leading to bacteriological diagnosis as well as appropriate long-term antibiotic therapy. All had good recovery at 6 months after completion of treatment.

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 and 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.