-
PLoS Neglected Tropical Diseases Jun 2017Melioidosis is a life threatening infectious disease caused by the gram-negative bacillus Burkholderia pseudomallei predominantly found in southeast Asia and northern...
BACKGROUND
Melioidosis is a life threatening infectious disease caused by the gram-negative bacillus Burkholderia pseudomallei predominantly found in southeast Asia and northern Australia. Studying the host transcription profiles in response to infection is crucial for understanding disease pathogenesis and correlates of disease severity, which may help improve therapeutic intervention and survival. The aim of this study was to analyze gene expression levels of human host factors in melioidosis patients and establish useful correlation with disease biomarkers, compared to healthy individuals and patients with sepsis caused by other pathogens.
METHODS
The study population consisted of 30 melioidosis cases, 10 healthy controls and 10 sepsis cases caused by other pathogens. Total RNA was extracted from peripheral blood mononuclear cells (PBMC's) of study subjects. Gene expression profiles of 25 gene targets including 19 immune response genes and 6 epigenetic factors were analyzed by real time quantitative polymerase chain reaction (RT-qPCR).
PRINCIPAL FINDINGS
Inflammatory response genes; TLR4, late onset inflammatory mediator HMGB1, genes associated with antigen presentation; MICB, PSMB2, PSMB8, PSME2, epigenetic regulators; DNMT3B, HDAC1, HDAC2 were significantly down regulated, whereas the anti-inflammatory gene; IL4 was up regulated in melioidosis patients compared to sepsis cases caused by other pathogens. Septicaemic melioidosis cases showed significant down regulation of IL8 compared to sepsis cases caused by other pathogens. HMGB1, MICB, PSMB8, PSMB2, PSME2, HDAC1, HDAC2 and DNMT3B showed consistent down regulation of gene expression in melioidosis patients compared to other sepsis infection, irrespective of comorbidities such as diabetes, duration of clinical symptoms and antibiotic treatment.
SIGNIFICANCE
Specific immune response genes and epigenetic regulators are differentially expressed among melioidosis patients and patients with sepsis caused by other pathogens. Therefore, these genes may serve as biomarkers for disease diagnosis to distinguish melioidosis from cases of sepsis due to other infections and therapeutic intervention for melioidosis.
Topics: Biomarkers; Diagnosis, Differential; Gene Expression Profiling; Genes, Regulator; Humans; Immunologic Factors; Melioidosis; Real-Time Polymerase Chain Reaction; Sri Lanka
PubMed: 28628607
DOI: 10.1371/journal.pntd.0005643 -
Journal of Infection in Developing... Jan 2017Melioidosis involving bone, joints, and soft tissue is rare and reported usually following dissemination of disease from infection elsewhere in the body; to a lesser...
INTRODUCTION
Melioidosis involving bone, joints, and soft tissue is rare and reported usually following dissemination of disease from infection elsewhere in the body; to a lesser degree, it can also be reported as the primary manifestation of melioidosis.
METHODOLOGY
The orthopedic registry at Hospital University Sains Malaysia from 2008 until 2014 was retrospectively reviewed and was followed by molecular typing of Burkholderia pseudomallei.
RESULTS
Out of 20 cases identified, 19 patients were confirmed to have osteoarticular and/or soft-tissue melioidosis. The majority of the patients were males (84%), and 16 patients had underlying diabetes mellitus with no significant estimated risk with the disease outcomes. Bacterial genotype was not associated with the disease as a risk. Death was a significant outcome in patients with bacteremic infections (p = 0.044).
CONCLUSION
Patients with lung or skin melioidosis require careful treatment follow-up to minimize the chance for secondary osteoarticular infection. Human risk factors remain the leading predisposing factors for melioidosis. Early laboratory and clinical diagnosis and acute-phase treatment can decrease morbidity and mortality.
Topics: Adolescent; Adult; Burkholderia pseudomallei; Child; Diabetes Complications; Female; Humans; Malaysia; Male; Melioidosis; Middle Aged; Molecular Typing; Osteoarthritis; Retrospective Studies; Risk Factors; Soft Tissue Infections; Survival Analysis; Young Adult
PubMed: 28141587
DOI: 10.3855/jidc.7612 -
PLoS Neglected Tropical Diseases Mar 2017Melioidosis, caused by bioterror treat agent Burkholderia pseudomallei, is an important cause of community-acquired Gram-negative sepsis in Southeast Asia and Northern...
BACKGROUND
Melioidosis, caused by bioterror treat agent Burkholderia pseudomallei, is an important cause of community-acquired Gram-negative sepsis in Southeast Asia and Northern Australia. New insights into the pathogenesis of melioidosis may help improve treatment and decrease mortality rates from this dreadful disease. We hypothesized that changes in Von Willebrand factor (VWF) function should occur in melioidosis, based on the presence of endothelial stimulation by endotoxin, pro-inflammatory cytokines and thrombin in melioidosis, and investigated whether this impacted on outcome.
METHODS/PRINCIPAL FINDINGS
We recruited 52 controls and 34 culture-confirmed melioidosis patients at Sappasithiprasong Hospital in Ubon Ratchathani, Thailand. All subjects were diabetic. Platelet counts in melioidosis patients were lower compared to controls (p = 0.0001) and correlated with mortality (p = 0.02). VWF antigen levels were higher in patients (geometric mean, 478 U/dl) compared to controls (166 U/dL, p<0.0001). The high levels of VWF in melioidosis appeared to be due to increased endothelial stimulation (VWF propeptide levels were elevated, p<0.0001) and reduced clearance (ADAMTS13 reduction, p<0.0001). However, VWF antigen levels did not correlate with platelet counts implying that thrombocytopenia in acute melioidosis has an alternative cause.
CONCLUSIONS/SIGNIFICANCE
Thrombocytopenia is a key feature of melioidosis and is correlated with mortality. Additionally, excess VWF and ADAMTS13 deficiency are features of acute melioidosis, but are not the primary drivers of thrombocytopenia in melioidosis. Further studies on the role of thrombocytopenia in B. pseudomallei infection are needed.
Topics: ADAMTS13 Protein; Adolescent; Adult; Aged; Burkholderia pseudomallei; Female; Humans; Male; Melioidosis; Middle Aged; Survival Analysis; Thailand; Thrombocytopenia; Young Adult; von Willebrand Factor
PubMed: 28296884
DOI: 10.1371/journal.pntd.0005468 -
Tropical Medicine & International... Jun 2021Melioidosis, caused by Burkholderia pseudomallei, is prevalent in rural areas of Malaysia. The aim of this study is to delineate the epidemiology and predictors of...
OBJECTIVES
Melioidosis, caused by Burkholderia pseudomallei, is prevalent in rural areas of Malaysia. The aim of this study is to delineate the epidemiology and predictors of mortality from melioidosis in Kapit district, Sarawak.
METHODS
For this retrospective study of patients with culture-confirmed melioidosis admitted to Kapit Hospital, Sarawak, Malaysia, between July 2016 and July 2019, epidemiological, clinical and microbiological data were obtained. Univariate and multivariate logistic regression analyses were used to determine predictors of mortality.
RESULTS
Seventy three patients met inclusion criteria. Diabetes mellitus (28.8%) and hypertension (27.4%) were primary co-morbidities. Clinical spectrum of melioidosis ranged from bacteraemia (64.4%), pneumonia (61.6%) and internal organ abscesses (49.3%) to localised soft tissue (21.9%) and joint abscesses (6.9%). Mortality rate was 12.3%. Bacteraemia and pneumonia were significantly associated with septic shock, whereas patients with soft tissue abscesses tended to present with a milder form of melioidosis without septic shock. Septic shock, mechanical ventilation, intensive care unit admission, serum urea, creatinine, bicarbonate, albumin and aspartate transaminase were all significantly associated with increased mortality on univariate analysis (all P < 0.05). Multivariate analysis revealed that low serum bicarbonate (P = 0.004, OR 0.64, 95% CI 0.48-0.87) and albumin (P = 0.031, OR 0.73, 95% CI 0.54-0.97) could be associated with a higher mortality.
CONCLUSION
Melioidosis remains a fatal infection and commonly presents with septic shock, in the form of bacteraemia and pneumonia. Two routine clinical parameters, serum bicarbonate and serum albumin, may have important prognostic implications in septicaemic melioidosis.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacteremia; Bicarbonates; Biomarkers; Burkholderia pseudomallei; Comorbidity; Female; Humans; Malaysia; Male; Melioidosis; Middle Aged; Pneumonia; Retrospective Studies; Serum Albumin; Shock, Septic; Young Adult
PubMed: 33590932
DOI: 10.1111/tmi.13563 -
PLoS Neglected Tropical Diseases Oct 2023Melioidosis is a deadly endemic disease in northern Australia and Southeast Asia, including Sabah, Malaysia, which is caused by the bacterium Burkholderia pseudomallei....
INTRODUCTION
Melioidosis is a deadly endemic disease in northern Australia and Southeast Asia, including Sabah, Malaysia, which is caused by the bacterium Burkholderia pseudomallei. It contributes to high fatality rates, mainly due to misdiagnosis leading to the wrong treatment being administered to the patients. Local epidemiology and data on clinical features could assist clinicians during diagnosis and treatment. However, these details are still scarce, particularly in Sabah.
METHODS
A retrospective study of 246 culture-confirmed melioidosis cases in Queen Elizabeth Hospital, Sabah, Malaysia was performed between 2016 and 2018. The epidemiological data and clinical and laboratory findings were extracted and analysed.
RESULTS
The annual incidence of culture-confirmed melioidosis cases was estimated to be 4.97 per 100,000 people. The mean age of the patients was 50±15 years. Males and members of the Kadazan-Dusun ethnic group accounted for the majority of the melioidosis cases. The odds ratio analysis indicated that bacteraemic melioidosis in this region was significantly associated with fever (76%), and patients having at least one underlying illness (43%), including diabetes mellitus (32%). Sixty-eight patients (28%) succumbed to melioidosis. Contrary to what is known regarding factors that promote bacteraemic melioidosis, neither patients with fever nor patients with at least one comorbid disease, including diabetes mellitus, were significantly associated with death from melioidosis. There was no statistically significant difference between patients without comorbidities (24, 27%) and those with at least one comorbid disease (26, 25%), including diabetes mellitus (18, 23%). The odds ratios indicate that melioidosis mortality in this region is related to patients showing respiratory organ-associated symptoms (29%), bacteraemia (30%), and septic shock (47%). Burkholderia pseudomallei isolates in this study were highly susceptible to ceftazidime (100%), imipenem (100%), and trimethoprim-sulfamethoxazole (98%).
CONCLUSIONS
Information obtained from this study can be used by clinicians to recognise individuals with the highest risk of acquiring melioidosis, estimate an accurate prognosis, and provide effective treatment for melioidosis patients to reduce death from melioidosis.
Topics: Male; Humans; Adult; Middle Aged; Aged; Melioidosis; Malaysia; Anti-Bacterial Agents; Retrospective Studies; Burkholderia pseudomallei; Diabetes Mellitus; Treatment Outcome; Bacteremia
PubMed: 37844130
DOI: 10.1371/journal.pntd.0011696 -
PloS One 2013Melioidosis (Burkholderia pseudomallei infection) is a common cause of community-acquired sepsis in Northeast Thailand and northern Australia. B. pseudomallei is a soil...
Melioidosis (Burkholderia pseudomallei infection) is a common cause of community-acquired sepsis in Northeast Thailand and northern Australia. B. pseudomallei is a soil saprophyte endemic to Southeast Asia and northern Australia. The clinical presentation of melioidosis may mimic tuberculosis (both cause chronic suppurative lesions unresponsive to conventional antibiotics and both commonly affect the lungs). The two diseases have overlapping risk profiles (e.g., diabetes, corticosteroid use), and both B. pseudomallei and Mycobacterium tuberculosis are intracellular pathogens. There are however important differences: the majority of melioidosis cases are acute, not chronic, and present with severe sepsis and a mortality rate that approaches 50% despite appropriate antimicrobial therapy. By contrast, tuberculosis is characteristically a chronic illness with mortality <2% with appropriate antimicrobial chemotherapy. We examined the gene expression profiles of total peripheral leukocytes in two cohorts of patients, one with acute melioidosis (30 patients and 30 controls) and another with tuberculosis (20 patients and 24 controls). Interferon-mediated responses dominate the host response to both infections, and both type 1 and type 2 interferon responses are important. An 86-gene signature previously thought to be specific for tuberculosis is also found in melioidosis. We conclude that the host responses to melioidosis and to tuberculosis are similar: both are dominated by interferon-signalling pathways and this similarity means gene expression signatures from whole blood do not distinguish between these two diseases.
Topics: Acute Disease; Adolescent; Adult; Aged; Cohort Studies; Female; Gene Expression Profiling; Genomics; Humans; Interferons; Leukocytes; Male; Melioidosis; Middle Aged; Signal Transduction; Tuberculosis, Pulmonary; Young Adult
PubMed: 23383015
DOI: 10.1371/journal.pone.0054961 -
The Bone & Joint Journal Feb 2015Little information is available about several important aspects of the treatment of melioidosis osteomyelitis and septic arthritis. We undertook a retrospective review...
Little information is available about several important aspects of the treatment of melioidosis osteomyelitis and septic arthritis. We undertook a retrospective review of 50 patients with these conditions in an attempt to determine the effect of location of the disease, type of surgical intervention and duration of antibiotic treatment on outcome, particularly complications and relapse. We found that there was a 27.5% risk of osteomyelitis of the adjacent bone in patients with septic arthritis in the lower limb. Patients with septic arthritis and osteomyelitis of an adjacent bone were in hospital significantly longer (p = 0.001), needed more operations (p = 0.031) and had a significantly higher rate of complications and re-presentation (p = 0.048). More than half the patients (61%), most particularly those with multifocal bone and joint involvement, and those with septic arthritis and osteomyelitis of an adjacent bone who were treated operatively, needed more visits to theatre.
Topics: Adult; Anti-Bacterial Agents; Arthritis, Infectious; Combined Modality Therapy; Comorbidity; Female; Humans; Male; Melioidosis; Middle Aged; Osteomyelitis
PubMed: 25628295
DOI: 10.1302/0301-620X.97B2.34799 -
The Medical Journal of Malaysia Mar 2021Melioidosis is endemic in Sabah. It causes significant morbidity and mortality if diagnosis and treatment is delayed. Important risk factors include diabetes, chronic...
Melioidosis is endemic in Sabah. It causes significant morbidity and mortality if diagnosis and treatment is delayed. Important risk factors include diabetes, chronic kidney diseases, chronic lung diseases, thalassaemia, immunosuppressive therapy, and hazardous alcohol consumption. Influenza A is usually a self-limiting disease but is associated with high morbidity and mortality in highrisk populations especially during pregnancy. Both melioidosis and influenza A commonly present in patients with pneumonia. Secondary bacterial pneumonia is a known complication in approximately one third of patients with severe pneumonia due to influenza A, resulting in intensive care unit admissions. However, melioidosis is not commonly recognized as an aetiology in secondary bacterial pneumonia complicating influenza A infection. This is important as empirical antibiotics that are used to treat secondary bacterial pneumonia due to influenza A often do not cover melioidosis. Here we report a rare case of concurrent pulmonary melioidosis and influenza A in a 30- year-old primigravida at 27 weeks of pregnancy in the Queen Elizabeth Hospital, Sabah, Malaysia to highlight the challenge in the recognition and management of both infections in a melioidosis endemic area.
Topics: Adult; Anti-Bacterial Agents; Burkholderia pseudomallei; Female; Humans; Influenza, Human; Melioidosis; Pneumonia, Bacterial; Pregnancy
PubMed: 33742637
DOI: No ID Found -
PLoS Neglected Tropical Diseases Dec 2016Melioidosis is a tropical infectious disease associated with significant mortality due to early onset of sepsis. (Review)
Review
BACKGROUND
Melioidosis is a tropical infectious disease associated with significant mortality due to early onset of sepsis.
OBJECTIVE
We sought to review case reports of melioidosis from Malaysia.
METHODS
We conducted a computerized search of literature resources including PubMed, OVID, Scopus, MEDLINE and the COCHRANE database to identify published case reports from 1975 to 2015. We abstracted information on clinical characteristics, exposure history, comorbid conditions, management and outcome.
RESULTS
Overall, 67 cases were reported with 29 (43%) deaths; the median age was 44 years, and a male preponderance (84%) was noted. Forty-one cases (61%) were bacteremic, and fatal septic shock occurred in 13 (19%) within 24-48 hours of admission; nine of the 13 cases were not specifically treated for melioidosis as confirmatory evidence was available only after death. Diabetes mellitus (n = 36, 54%) was the most common risk factor. Twenty-six cases (39%) had a history of exposure to contaminated soil/water or employment in high-risk occupations. Pneumonia (n = 24, 36%) was the most common primary clinical presentation followed by soft tissue abscess (n = 22, 33%). Other types of clinical presentations were less common-genitourinary (n = 5), neurological (n = 5), osteomyelitis/septic arthritis (n = 4) and skin (n = 2); five cases had no evidence of a focus of infection. With regard to internal foci of infection, abscesses of the subcutaneous tissue (n = 14, 21%) was the most common followed by liver (18%); abscesses of the spleen and lung were the third most common (12% each). Seven of 56 males were reported to have prostatic abscesses. Mycotic pseudoaneurysm occurred in five cases. Only one case of parotid abscess was reported in an adult. Of the 67 cases, 13 were children (≤ 18 years of age) with seven deaths; five of the 13 were neonates presenting primarily with bronchopneumonia, four of whom died. Older children had a similar presentation as adults; no case of parotid abscess was reported among children.
CONCLUSIONS
The clinical patterns of cases reported from Malaysia are consistent for the most part from previous case reports from South and Southeast Asia with regard to common primary presentations of pneumonia and soft tissue abscesses, and diabetes as a major risk factor. Bacteremic melioidosis carried a poor prognosis and septic shock was strong predictor of mortality. Differences included the occurrence of: primary neurological infection was higher in Malaysia compared to reports outside Malaysia; internal foci of infection such as abscesses of the liver, spleen, prostate, and mycotic pseudoaneurysms were higher than previously reported in the region. No parotid abscess was reported among children. Early recognition of the disease is the cornerstone of management. In clinical situations of community-acquired sepsis and/or pneumonia, where laboratory bacteriological confirmation is not possible, empirical treatment with antimicrobials for B. pseudomallei is recommended.
Topics: Adult; Bacteremia; Burkholderia pseudomallei; Child; Diabetes Mellitus; Female; Humans; Infant, Newborn; Malaysia; Male; Melioidosis; Risk Factors; Young Adult
PubMed: 28005910
DOI: 10.1371/journal.pntd.0005182 -
Journal of Infection in Developing... Jun 2023A 12-year-old boy was admitted after 11 days of fever and 2 days of nasal obstruction as well as swelling of a right cervical lymph node. Nasal endoscopy and computed...
A 12-year-old boy was admitted after 11 days of fever and 2 days of nasal obstruction as well as swelling of a right cervical lymph node. Nasal endoscopy and computed tomography of the neck showed a nasopharyngeal mass occupying the entire nasopharynx, extending into the nasal cavity, and obliterating the fossa of Rosenmuller. Abdominal ultrasonography revealed a small solitary splenic abscess. Although a nasopharyngeal tumor or malignancy was initially considered, biopsy of the mass showed only suppurative granulomatous inflammation, and bacterial culture from the enlarged cervical lymph node yielded Burkholderia pseudomallei. The symptoms, nasopharyngeal mass, and cervical lymph node enlargement resolved with melioidosis-directed antibiotic therapy. Although rarely reported, the nasopharynx may be an important primary site of infection in melioidosis patients, especially in pediatric patients.
Topics: Male; Humans; Child; Melioidosis; Splenic Diseases; Nasopharyngeal Neoplasms; Burkholderia pseudomallei; Anti-Bacterial Agents; Lymphadenopathy; Nasopharynx
PubMed: 37406064
DOI: 10.3855/jidc.17821