Relationship of cerebrospinal fluid pressure, fungal burden and outcome in patients with cryptococcal meningitis undergoing serial lumbar punctures.

Objectives: To assess impact of serial lumbar punctures on association between cerebrospinal fluid (CSF) opening pressure and prognosis in HIV-associated cryptococcal meningitis; to explore time course and relationship of opening pressure with neurological findings, CSF fungal burden, immune response, and CD4 cell count.

Design: Evaluation of 163 HIV-positive ART-naive patients enrolled in three trials of amphotericin B-based therapy for cryptococcal meningitis in Thailand and South Africa.

Methods: Study protocols required four lumbar punctures with measurements of opening pressure over the first 2 weeks of treatment and additional lumbar punctures if opening pressure raised.

Staphylococcus aureus bacteraemia in a tropical setting: patient outcome and impact of antibiotic resistance.

Background: Most information on invasive Staphylococcus aureus infections comes from temperate countries. There are considerable knowledge gaps in epidemiology, treatment, drug resistance and outcome of invasive S. aureus infection in the tropics.

Intensity of exposure and incidence of melioidosis in Thai children.

There is a high background seroprevalence of antibodies to Burkholderia pseudomallei in Thailand that limits its use as a diagnostic tool. It is believed that this results from childhood exposure to the bacterium in mud and surface water. The increasing prevalence of antibodies with age is a marker of the intensity of exposure.

Rheumatological manifestations in patients with melioidosis.

Melioidosis, an infection caused by the bacterium Burkholderia pseudomallei, has a wide range of clinical manifestations. Here, we describe rheumatological melioidosis (involving one or more of joint, bone or muscle), and compare features and outcome with patients without rheumatological involvement. A retrospective study of patients with culture-confirmed melioidosis admitted to Sappasithiprasong Hospital, Ubon Ratchathani during 2002 and 2005 identified 679 patients with melioidosis, of whom 98 (14.

A simple scoring system to differentiate between relapse and re-infection in patients with recurrent melioidosis.

Background: Melioidosis is an important cause of morbidity and mortality in East Asia. Recurrent melioidosis occurs in around 10% of patients following treatment either because of relapse with the same strain or re-infection with a new strain of Burkholderia pseudomallei. Distinguishing between the two is important but requires bacterial genotyping.

Strategies to reduce mortality from bacterial sepsis in adults in developing countries.

Sharon Peacock and colleagues discuss management of adult patients with sepsis in low- and middle-income settings, with a particular emphasis on tropical regions.

Burkholderia pseudomallei genome plasticity associated with genomic island variation.

Background: Burkholderia pseudomallei is a soil-dwelling saprophyte and the cause of melioidosis. Horizontal gene transfer contributes to the genetic diversity of this pathogen and may be an important determinant of virulence potential. The genome contains genomic island (GI) regions that encode a broad array of functions.

Genetic diversity and microevolution of Burkholderia pseudomallei in the environment.

Background: The soil dwelling Gram-negative pathogen Burkholderia pseudomallei is the cause of melioidosis. The diversity and population structure of this organism in the environment is poorly defined.

Methods And Findings: We undertook a study of B.

Consensus guidelines for dosing of amoxicillin-clavulanate in melioidosis.

Melioidosis is an infectious disease endemic to northern Australia and Southeast Asia. In response to clinical confusion regarding the appropriate dose of amoxicillin-clavulanate, we have developed guidelines for the appropriate dosing of this second-line agent. For eradication therapy for melioidosis, we recommend 20/5 mg/kg orally, three times daily.

Direct in vivo assessment of microcirculatory dysfunction in severe falciparum malaria.

Background: This study sought to describe and quantify microcirculatory changes in the mucosal surfaces of patients with severe malaria, by direct in vivo observation using orthogonal polarization spectral (OPS) imaging.

Methods: The microcirculation in the rectal mucosa of adult patients with severe malaria was assessed by use of OPS imaging, at admission and then daily. Comparison groups comprised patients with uncomplicated falciparum malaria, patients with bacterial sepsis, and healthy individuals.

Loop-mediated isothermal amplification method targeting the TTS1 gene cluster for detection of Burkholderia pseudomallei and diagnosis of melioidosis.

Melioidosis is a severe infection caused by Burkholderia pseudomallei. The timely implementation of effective antimicrobial treatment requires rapid diagnosis. Loop-mediated isothermal amplification (LAMP) targeting the TTS1 gene cluster was developed for the detection of B.

Evaluating Burkholderia pseudomallei Bip proteins as vaccines and Bip antibodies as detection agents.

Burkholderia pseudomallei is a biothreat agent and an important natural pathogen, causing melioidosis in humans and animals. A type III secretion system (TTSS-3) has been shown to be critical for virulence. Because TTSS components from other pathogens have been used successfully as diagnostic agents and as experimental vaccines, it was investigated whether this was the case for BipB, BipC and BipD, components of B.

Prospective clinical evaluation of the accuracy of 16S rRNA real-time PCR assay for the diagnosis of melioidosis.

The accuracy of a Burkholderia pseudomallei 16s rRNA real-time PCR assay was evaluated against culture for the diagnosis of melioidosis in Thailand. A total of 846 samples were obtained from 383 patients with suspected melioidosis. One or more specimens were PCR positive for 47 of 77 patients with culture-proven melioidosis (sensitivity 61.

Quantitation of B. Pseudomallei in clinical samples.

We undertook a prospective study to quantitate Burkholderia pseudomallei in blood, urine, respiratory secretions, and pus [corrected] obtained from 414 patients with melioidosis. The median was count 1.1, 1.

Invasive Erysipelothrix rhusiopathiae infection in northeast Thailand.

Three cases of invasive Erysipelothrix rhusipathiae infection, which is considered rare, presented to a hospital in Ubon Ratchathani, northeast Thailand during 2006. Patients presented with variable clinical manifestations including diffused cutaneous lesions, bacteremia and endocarditis. Erysipelothrix infection may be an emerging infection in immunocompromized individuals in Thailand.

Simultaneous infection with more than one strain of Burkholderia pseudomallei is uncommon in human melioidosis.

A prospective study was performed to determine the rate at which patients with melioidosis are infected with more than one strain of Burkholderia pseudomallei. Genotyping of 2,058 bacterial colonies isolated from 215 samples taken from 133 patients demonstrated that mixed infection is uncommon (2/133 cases [1.5%; 95% confidence interval, 0.

Toll-like receptor 2 impairs host defense in gram-negative sepsis caused by Burkholderia pseudomallei (Melioidosis).

Background: Toll-like receptors (TLRs) are essential in host defense against pathogens by virtue of their capacity to detect microbes and initiate the immune response. TLR2 is seen as the most important receptor for gram-positive bacteria, while TLR4 is regarded as the gram-negative TLR. Melioidosis is a severe infection caused by the gram-negative bacterium, Burkholderia pseudomallei, that is endemic in Southeast Asia.

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.

A randomized controlled trial of granulocyte colony-stimulating factor for the treatment of severe sepsis due to melioidosis in Thailand.

Background: Melioidosis is a tropical infectious disease associated with significant mortality. Most deaths occur early and are caused by fulminant sepsis.

Methods: In this randomized, placebo-controlled trial, we assessed the efficacy of lenograstim (granulocyte colony-stimulating factor [G-CSF], 263 mu g per day administered intravenously) in ceftazidime-treated patients with severe sepsis caused by suspected melioidosis in Thailand.

Metastatic mucinous cystic adenocarcinoma of the pancreas presenting as Sister Mary Joseph's nodule.

Context: Sister Mary Joseph's nodule usually represents metastatic cancers from gastrointestinal malignancy including adenocarcinoma of the pancreas. Mucinous cystadenocarcinoma is a rare malignancy of the pancreas. However, pancreatic mucinous cystadenocarcinoma metastasized to Sister Mary Joseph's nodule is much rarer and has never been reported before.

High-throughput mRNA profiling characterizes the expression of inflammatory molecules in sepsis caused by Burkholderia pseudomallei.

Sepsis is characterized by an uncontrolled inflammatory response to invading microorganisms. We describe the inflammatory mRNA profiles in whole-blood leukocytes, monocytes, and granulocytes using a multigene system for 35 inflammatory markers that included pro- and anti-inflammatory cytokines, chemokines, and signal transduction molecules in a case-control study with 34 patients with sepsis caused by the gram-negative bacterium Burkholderia pseudomallei (the pathogen causing melioidosis) and 32 healthy volunteers. Relative to healthy controls, patients with sepsis showed increased transcription of a whole array of inflammatory genes in peripheral blood leukocytes, granulocytes, and monocytes.

Optimization of culture of Leptospira from humans with leptospirosis.

A prospective study of 989 patients with acute febrile illness was performed in northeast Thailand to define the yield of Leptospira from four different types of blood sample. Based on a comparison of the yields from whole blood, surface plasma, deposit from spun plasma, and clotted blood samples from 80 patients with culture-proven leptospirosis, we suggest a sampling strategy in which culture is performed using whole blood and deposit from spun plasma.

Biological relevance of colony morphology and phenotypic switching by Burkholderia pseudomallei.

Melioidosis is a notoriously protracted illness and is difficult to cure. We hypothesize that the causative organism, Burkholderia pseudomallei, undergoes a process of adaptation involving altered expression of surface determinants which facilitates persistence in vivo and that this is reflected by changes in colony morphology. A colony morphotyping scheme and typing algorithm were developed using clinical B.

Accuracy of enzyme-linked immunosorbent assay using crude and purified antigens for serodiagnosis of melioidosis.

Five enzyme-linked immunosorbent assays developed to detect antibodies to different Burkholderia pseudomallei antigen preparations were evaluated as diagnostic tests for melioidosis in northeast Thailand. The highest diagnostic indices were observed for an affinity-purified antigen (sensitivity, 82%; specificity, 72%) and crude B. pseudomallei antigen (sensitivity, 81%; specificity, 70%), an improvement over the indirect hemagglutination assay (sensitivity, 73%; specificity, 64%).

Risk factors for recurrent melioidosis in northeast Thailand.

Background: Recurrent melioidosis occurs in approximately 6% of patients in the first year following the initial presentation. A recent study revealed that 25% of patients with recurrence had reinfection rather than a relapse resulting from a failure to cure. The aim of this study was to reevaluate these 2 patient groups to define their individual risk factors.