Neurological Melioidosis Research Articles

Cerebral melioidosis for the first time in the western hemisphere

This report is the first published case of cerebral melioidosis in the western hemisphere. In this paper the authors review the literature on neurological melioidosis and its presentation and treatment in endemic areas, describe the clinical course of this unique case of a presentation of the disease with cranial abscess in the US, review the pathological and radiological findings associated with this seminal case, and put forth recommendations for recognizing and treating possible future instances of the disease within the western hemisphere.

Guillain Barre syndrome as a manifestation of neurological melioidosis

Neurological melioidosis is a very rare and very few cases have been reported from India. Presentation is an extremely varied and as this disease is associated with high mortality, high index of suspicion is needed to diagnose and treat. In this context, we report a patient presenting as Guillain Barre syndrome evaluated as melioidosis.

Neurologic Melioidosis in a Child

We present the case of a child who exemplifies the difficulties in diagnosing neurologic melioidosis.

The Epidemiology and Clinical Spectrum of Melioidosis: 540 Cases from the 20 Year Darwin Prospective Study

BackgroundOver 20 years, from October 1989, the Darwin prospective melioidosis study has documented 540 cases from tropical Australia, providing new insights into epidemiology and the clinical spectrum.Principal FindingsThe principal presentation was pneumonia in 278 (51%), genitourinary infection in 76 (14%), skin infection in 68 (13%), bacteremia without evident focus in 59 (11%), septic arthritis/osteomyelitis in 20 (4%) and neurological melioidosis in 14 (3%). 298 (55%) were bacteremic and 116 (21%) developed septic shock (58 fatal). Internal organ abscesses and secondary foci in lungs and/or joints were common. Prostatic abscesses occurred in 76 (20% of 372 males). 96 (18%) had occupational exposure to Burkholderia pseudomallei. 118 (22%) had a specific recreational or occupational incident considered the likely infecting event. 436 (81%) presented during the monsoonal wet season. The higher proportion with pneumonia in December to February supports the hypothesis of infection by inhalation during severe weather events. Recurrent melioidosis occurred in 29, mostly attributed to poor adherence to therapy. Mortality decreased from 30% in the first 5 years to 9% in the last five years (p<0.001). Risk factors for melioidosis included diabetes (39%), hazardous alcohol use (39%), chronic lung disease (26%) and chronic renal disease (12%). There was no identifiable risk factor in 20%. Of the 77 fatal cases (14%), 75 had at least one risk factor; the other 2 were elderly. On multivariate analysis of risk factors, age, location and season, the only independent predictors of mortality were the presence of at least one risk factor (OR 9.4; 95% CI 2.3–39) and age ≥50 years (OR 2.0; 95% CI 1.2–2.3).ConclusionsMelioidosis should be seen as an opportunistic infection that is unlikely to kill a healthy person, provided infection is diagnosed early and resources are available to provide appropriate antibiotics and critical care.

Nasal‐Associated Lymphoid Tissue and Olfactory Epithelium as Portals of Entry forBurkholderia pseudomalleiin Murine Melioidosis

Burkholderia pseudomallei, the causative agent of melioidosis, is generally considered to be acquired via inhalation of dust or water droplets from the environment. In this study, we show that infection of the nasal mucosa is potentially an important portal of entry in melioidosis. After intranasal inoculation of mice, infection was monitored by bioluminescence imaging and by immunohistological analysis of coronal sections. The bacterial loads in organ and tissue specimens were also monitored. Bioluminescence imaging showed colonization and replication in the nasal cavity, including the nasal-associated lymphoid tissue (NALT). Analysis of coronal sections and immunofluorescence microscopy further demonstrated the presence of infection in the respiratory epithelium and the olfactory epithelium (including associated nerve bundles), as well as in the NALT. Of significance, the olfactory epithelium and the brain were rapidly infected before bacteria were detected in blood, and a capsule-deficient mutant infected the brain without significantly infecting blood. These data suggest that the olfactory nerve is the route of entry into the brain and that this route of entry may be paralleled in cases of human neurologic melioidosis. This study focuses attention on the upper respiratory tract as a portal of entry, specifically focusing on NALT as a route for the development of systemic infection via the bloodstream and on the olfactory epithelium as a direct route to the brain.

Paediatric melioidosis in North Queensland, Australia

to review admissions to the hospital due to Paediatric Melioidosis over a 10 year period. This was a retrospective chart review of all paediatric patients admitted to Townsville Hospital between 1996 and 2006 that were proven to have positive cultures for B. pseudomallei. Details were obtained from the Microbiology Department of Townsville Hospital. Between 1996 and 2006, there were 150 cases of culture-confirmed melioidosis in North Queensland. Of these, eight (5.3%) were in children aged under 16 years. There were three deaths in this group. Three patients developed neurological melioidosis and there were no cases of parotid involvement. In our series, neurological melioidosis appeared to be statistically more significant in children compared with adults. Melioidosis is an uncommon paediatric infection in Australia. In our series, neurological melioidosis appeared to be common in children compared with adults with devastating sequelae. The reasons for this remain unclear.

Variable Presentation of Neurological Melioidosis in Northeast Thailand

We describe three instructive cases of neurologic melioidosis that demonstrate the variable nature of clinical manifestations and disease pathology. The appropriate duration and choice of parenteral and oral antimicrobial therapy for neurologic melioidosis are also discussed.

Use of a Variable Amplicon Typing Scheme Reveals Considerable Variation in the Accessory Genomes of Isolates of Burkholderia pseudomallei

Melioidosis, a disease caused by the bacterium Burkholderia pseudomallei, is endemic in southeast Asia and northern Australia. We used suppression subtractive hybridization (SSH) to identify sequences that varied between two B. pseudomallei isolates from Australia and determined the distribution of 45 SSH-derived sequences among a panel of B. pseudomallei and B. thailandensis isolates. Sequences exhibiting variable prevalence were included in a variable amplicon typing (VAT) scheme designed to score the presence or absence of 14 PCR amplicons. VAT analysis was carried out with 48 isolates from Thailand, which were typed by multilocus sequence typing (MLST), and 44 isolates from Australia of known MLST type. The VAT scheme could be used to divide the 48 isolates from Thailand into 23 VAT types and the 44 isolates from Australia into 36 VAT types. Some of the sequences included in the VAT scheme were more commonly PCR positive among isolates from Australia than among isolates from Thailand, and vice versa. No isolate from Australia was PCR positive for genomic island 11 or a putative transposase sequence, whereas four SSH-derived sequences were far more prevalent among the Australian isolates. Analysis based on the VAT scheme indicated that the isolates clustered into groups, some of which were mainly or exclusively from one geographical origin. One cluster included Australian isolates that were mostly associated with severe disease, including rare neurological melioidosis, suggesting that the content of the accessory genome may play an important role in determining the clinical manifestation of the disease.

Burkholderia pseudomallei strain type, based on pulsed-field gel electrophoresis, does not determine disease presentation in melioidosis

Melioidosis, the infection due to Burkholderia pseudomallei, may present with a spectrum of severity and may affect any site in the body. Differential strain virulence and tropism suggested by previous studies would have implications for virulence and vaccine work. We explored clinical correlations using pulsed-field gel electrophoresis (PFGE) typing in a well-characterised clinical collection. Two methods of analysis were used based on band-based similarity values: first, a conventional cluster analysis formed by the unweighted paired group mean analysis, and second, an analysis of the distribution of the “within-group” and “between-group” Dice coefficient. Clinical isolates from 114 cases of melioidosis occurring in the Northern Territory, Australia were studied; 71 strain types were defined with a Simpson’s index of 0.91. No correlation was found between strain type and disease severity or site of melioidosis on presentation, with no differences in similarity values found when comparing within and between-groups. In particular, isolates from patients with neurological melioidosis were not clustered. There was evidence of geographical localisation. This study suggests that the variation in strain type may not be as important as host and environmental factors in determining the pattern of disease.

Paediatric melioidosis in the Northern Territory of Australia: an expanding clinical spectrum.

The objective of this study was to present the laboratory and clinical features of the six cases of paediatric melioidosis diagnosed from 1997-2000. All cases of melioidosis confirmed by the pathology department of Royal Darwin Hospital were prospectively identified by culture and/or serology. Four children were Aboriginal and all six cases presented during the rainy season (November-April) in rural areas in the tropical Top End of the Northern Territory. Delay in diagnosis ranged from 5 and 11 days. Two cases had localized melioidosis, two cases had underlying disease and were likely to be colonized with Burkholderia pseudomallei (B. pseudomallei). Two cases had neurological melioidosis with major residual disability. No deaths occurred. Melioidosis remains an unusual disease in children in the tropical Northern Territory. The average annual incidence since 1997 is 5.48 per 100 000. This series demonstrates that children in Australia can have serious neurological complications from B. pseudomallei infection. All children living in or visiting tropical Australia are at risk, especially those residing in rural areas in the rainy season. Melioidosis remains a difficult disease to manage, and expert opinion should be sought if B. pseudomallei is cultured from any site.