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Neurology India 2022Melioidosis is an emerging tropical disease. Central nervous system (CNS) melioidosis may present as a brain abscess or encephalomyelitis mimics tuberculosis. Early...
Melioidosis is an emerging tropical disease. Central nervous system (CNS) melioidosis may present as a brain abscess or encephalomyelitis mimics tuberculosis. Early diagnosis and management decreases mortality as well as morbidity. This case of brain abscess and encephalomyelitis in a young man with no known comorbidities was a diagnostic challenge. The surgery helped in debulking as well as isolating the causative organism. Appropriate antibiotic therapy for melioidosis was lifesaving and prevented further complications.
Topics: Anti-Bacterial Agents; Brain Abscess; Burkholderia pseudomallei; Central Nervous System; Encephalomyelitis; Humans; Male; Melioidosis
PubMed: 35532659
DOI: 10.4103/0028-3886.344620 -
PLoS Neglected Tropical Diseases Jun 2023This systematic review and network meta-analysis (NMA) aimed to compare the efficacy of all available treatments for severe melioidosis in decreasing hospital mortality... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This systematic review and network meta-analysis (NMA) aimed to compare the efficacy of all available treatments for severe melioidosis in decreasing hospital mortality and to identify eradication therapies with low disease recurrence rates and minimal risk of adverse drug events (AEs).
METHODOLOGY
Relevant randomized controlled trials (RCT) were searched from Medline and Scopus databases from their inception until July 31, 2022. RCTs that compared the efficacy between treatment regimens for severe melioidosis or eradication therapy of melioidosis, measured outcomes of in-hospital mortality, disease recurrence, drug discontinuation, or AEs, were included for review. A two-stage NMA with the surface under the cumulative ranking curve (SUCRA) was used to estimate the comparative efficacy of treatment regimens.
PRINCIPAL FINDINGS
Fourteen RCTs were included in the review. Ceftazidime plus granulocyte colony-stimulating factor (G-CSF), ceftazidime plus trimethoprim-sulfamethoxazole (TMP-SMX), and cefoperazone-sulbactam plus TMP-SMX had a lower mortality rate than other treatments and were ranked as the top three most appropriate treatments for severe melioidosis with the SUCRA of 79.7%, 66.6%, and 55.7%, respectively. However, these results were not statistically significant. For eradication therapy, treatment with doxycycline monotherapy for 20 weeks was associated with a significantly higher risk of disease recurrence than regimens containing TMP-SMX (i.e.,TMP-SMX for 20 weeks, TMP-SMX plus doxycycline plus chloramphenicol for more than 12 weeks, and TMP-SMX plus doxycycline for more than 12 weeks). According to the SUCRA, TMP-SMX for 20 weeks was ranked as the most efficacious eradication treatment (87.7%) with the lowest chance of drug discontinuation (86.4%), while TMP-SMX for 12 weeks had the lowest risk of AEs (95.6%).
CONCLUSION
Our results found a non-significant benefit of ceftazidime plus G-CSF and ceftazidime plus TMP-SMX over other treatments for severe melioidosis. TMP-SMX for 20 weeks was associated with a lower recurrence rate and minimal risk of adverse drug events compared to other eradication treatments. However, the validity of our NMA may be compromised by the limited number of included studies and discrepancies in certain study parameters. Thus, additional well-designed RCTs are needed to improve the therapy of melioidosis.
Topics: Humans; Trimethoprim, Sulfamethoxazole Drug Combination; Melioidosis; Doxycycline; Ceftazidime; Network Meta-Analysis; Granulocyte Colony-Stimulating Factor; Drug-Related Side Effects and Adverse Reactions
PubMed: 37307278
DOI: 10.1371/journal.pntd.0011382 -
Pathogens and Disease Aug 2016The Gram-negative proteobacteria genus Burkholderia encompasses multiple bacterial species that are pathogenic to humans and other vertebrates. Two pathogenic species of... (Review)
Review
The Gram-negative proteobacteria genus Burkholderia encompasses multiple bacterial species that are pathogenic to humans and other vertebrates. Two pathogenic species of interest within this genus are Burkholderia pseudomallei (Bpm) and the B. cepacia complex (Bcc); the former is the causative agent of melioidosis in humans and other mammals, and the latter is associated with pneumonia in immunocompromised patients. One understudied and shared characteristic of these two pathogenic groups is their ability to persist and establish chronic infection within the host. In this review, we will explore the depth of knowledge about chronic infections caused by persistent Bpm and Bcc. We examine the host risk factors and immune responses associated with more severe chronic infections. We also discuss host adaptation and phenotypes associated with persistent Burkholderia species. Lastly, we survey how other intracellular bacteria associated with chronic infections are combatted and explore possible future applications to target Burkholderia Our goal is to highlight understudied areas that should be addressed for a more thorough understanding of chronic Burkholderia infections and how to combat them.
Topics: Adaptation, Biological; Animals; Burkholderia; Burkholderia Infections; Chronic Disease; Host-Pathogen Interactions; Humans; Immune System; Melioidosis; Virulence Factors
PubMed: 27440810
DOI: 10.1093/femspd/ftw070 -
Clinical and Experimental Immunology May 2019Burkholderia pseudomallei is the causative agent of melioidosis. Historically believed to be a relatively rare human disease in tropical countries, a recent study... (Review)
Review
Burkholderia pseudomallei is the causative agent of melioidosis. Historically believed to be a relatively rare human disease in tropical countries, a recent study estimated that, worldwide, there are approximately 165 000 human melioidosis cases per year, more than half of whom die. The bacterium is inherently resistant to many antibiotics and treatment of the disease is often protracted and ineffective. There is no licensed vaccine against melioidosis, but a vaccine is predicted to be of value if used in high-risk populations. There has been progress over the last decade in the pursuit of an effective vaccine against melioidosis. Animal models of disease including mouse and non-human primates have been developed, and these models show that antibody responses play a key role in protection against melioidosis. Surprisingly, although B. pseudomallei is an intracellular pathogen there is limited evidence that CD8 T cells play a role in protection. It is evident that a multi-component vaccine, incorporating one or more protective antigens, will probably be essential for protection because of the pathogen's sophisticated virulence mechanisms as well as strain heterogeneity. Multi-component vaccines in development include glycoconjugates, multivalent subunit preparations, outer membrane vesicles and other nano/microparticle platforms and live-attenuated or inactivated bacteria. A consistent finding with vaccine candidates tested in mice is the ability to induce sterilizing immunity at low challenge doses and extended time to death at higher challenge doses. Further research to identify ways of eliciting more potent immune responses might provide a path for licensing an effective vaccine.
Topics: Animals; Antibodies, Bacterial; Antigens, Bacterial; Bacterial Vaccines; Burkholderia pseudomallei; CD8-Positive T-Lymphocytes; Humans; Melioidosis
PubMed: 30963550
DOI: 10.1111/cei.13286 -
Expert Opinion on Biological Therapy Dec 2019: Two important pathogenic species within the genus , namely () and (), are the causative agents of the life-threatening diseases melioidosis and glanders,... (Review)
Review
: Two important pathogenic species within the genus , namely () and (), are the causative agents of the life-threatening diseases melioidosis and glanders, respectively. Due to their high mortality rate and potential for aerosolization, they have gained interest as potential biothreat agents and are classified as Tier 1 Select Agents.: The manuscript provides an overview of the literature covering the efforts taken in the last 10 years to develop new therapeutics measures against both and , with attention on novel therapeutic agents.: As a result of the complicated antibiotic regimens necessary to treat these infections, development of novel therapeutics is needed to treat both diseases. In recent years, the understanding of the pathogenesis of has improved significantly and so have the efforts to develop novel therapeutic agents with high efficacy, either alone, or in combination with conventional antibiotics.
Topics: Animals; Biological Products; Burkholderia mallei; Burkholderia pseudomallei; Glanders; Humans; Melioidosis
PubMed: 31590578
DOI: 10.1080/14712598.2019.1677602 -
Emerging Infectious Diseases 2021We studied 20 confirmed or suspected cases of melioidosis in children in Ceará, Brazil, during 1989-2019. We observed a high death rate, severe signs and symptoms, and...
We studied 20 confirmed or suspected cases of melioidosis in children in Ceará, Brazil, during 1989-2019. We observed a high death rate, severe signs and symptoms, and substantial environmental exposure. These data suggest that childhood melioidosis might be more severe in Brazil than in other regions.
Topics: Brazil; Burkholderia pseudomallei; Child; Environmental Exposure; Humans; Melioidosis
PubMed: 34013871
DOI: 10.3201/eid2706.200154 -
Frontiers in Public Health 2023Melioidosis is a bacterial infection caused by (), posing a significant threat to public health. Rapid and accurate detection of is crucial for preventing and...
Melioidosis is a bacterial infection caused by (), posing a significant threat to public health. Rapid and accurate detection of is crucial for preventing and controlling melioidosis. However, identifying is challenging due to its high similarity to other species in the same genus. To address this issue, this study proposed a dual-target method that can specifically identify in less than 40 min. We analyzed 1722 genomes to construct large-scale pan-genomes and selected specific sequence tags in their core genomes that effectively distinguish from its closely related species. Specifically, we selected two specific tags, LC1 and LC2, which we combined with the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR associated proteins (Cas12a) system and recombinase polymerase amplification (RPA) pre-amplification. Our analysis showed that the dual-target RPA-CRISPR/Cas12a assay has a sensitivity of approximately 0.2 copies/reaction and 10 fg genomic DNA for LC1, and 2 copies/reaction and 20 fg genomic DNA for LC2. Additionally, our method can accurately and rapidly detect in human blood and moist soil samples using the specific sequence tags mentioned above. In conclusion, the dual-target RPA-CRISPR/Cas12a method is a valuable tool for the rapid and accurate identification of in clinical and environmental samples, aiding in the prevention and control of melioidosis.
Topics: Humans; Burkholderia pseudomallei; Melioidosis; CRISPR-Cas Systems
PubMed: 37250090
DOI: 10.3389/fpubh.2023.1153352 -
BMC Infectious Diseases Feb 2019Melioidosis is a life-threatening infectious disease that is caused by gram negative bacteria Burkholderia pseudomallei. This bacteria occurs as an environmental...
BACKGROUND
Melioidosis is a life-threatening infectious disease that is caused by gram negative bacteria Burkholderia pseudomallei. This bacteria occurs as an environmental saprophyte typically in endemic regions of south-east Asia and northern Australia. Therefore, patients with melioidosis are at high risk of being misdiagnosed and/or under-diagnosed in South Asia.
CASE PRESENTATION
Here, we report two cases of melioidosis from Nepal. Both of them were diabetic male who presented themselves with fever, multiple abscesses and developed sepsis. They were treated with multiple antimicrobial agents including antitubercular drugs before being correctly diagnosed as melioidosis. Consistent with this, both patients were farmer by occupation and also reported travelling to Malaysia in the past. The diagnosis was made consequent to the isolation of B. pseudomallei from pus samples. Accordingly, they were managed with intravenous meropenem followed by oral doxycycline and cotrimoxazole.
CONCLUSION
The case reports raise serious concern over the existing unawareness of melioidosis in Nepal. Both of the cases were left undiagnosed for a long time. Therefore, clinicians need to keep a high index of suspicion while encountering similar cases. Especially diabetic-farmers who present with fever and sepsis and do not respond to antibiotics easily may turn out to be yet another case of melioidosis. Ascertaining the travel history and occupational history is of utmost significance. In addition, the microbiologist should be trained to correctly identify B. pseudomallei as it is often confused for other Burkholderia species. The organism responds only to specific antibiotics; therefore, correct and timely diagnosis becomes crucial for better outcomes.
Topics: Abscess; Adult; Anti-Bacterial Agents; Burkholderia pseudomallei; Diabetes Mellitus; Diagnostic Errors; Doxycycline; Fever; Humans; Malaysia; Male; Melioidosis; Meropenem; Middle Aged; Nepal; Travel; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 30782129
DOI: 10.1186/s12879-019-3793-x -
PLoS Neglected Tropical Diseases Jun 2022Melioidosis is endemic in the remote Katherine region of northern Australia. In a population with high rates of chronic disease, social inequities, and extreme...
Melioidosis is endemic in the remote Katherine region of northern Australia. In a population with high rates of chronic disease, social inequities, and extreme remoteness, the impact of melioidosis is exacerbated by severe weather events and disproportionately affects First Nations Australians. All culture-confirmed melioidosis cases in the Katherine region of the Australian Top End between 1989-2021 were included in the study, and the clinical features and epidemiology were described. The diversity of Burkholderia pseudomallei strains in the region was investigated using genomic sequencing. From 1989-2021 there were 128 patients with melioidosis in the Katherine region. 96/128 (75%) patients were First Nations Australians, 72/128 (56%) were from a very remote region, 68/128 (53%) had diabetes, 57/128 (44%) had a history of hazardous alcohol consumption, and 11/128 (9%) died from melioidosis. There were 9 melioidosis cases attributable to the flooding of the Katherine River in January 1998; 7/9 flood-associated cases had cutaneous melioidosis, five of whom recalled an inoculating event injury sustained wading through flood waters or cleaning up after the flood. The 126 first-episode clinical B. pseudomallei isolates that underwent genomic sequencing belonged to 107 different sequence types and were highly diverse, reflecting the vast geographic area of the study region. In conclusion, melioidosis in the Katherine region disproportionately affects First Nations Australians with risk factors and is exacerbated by severe weather events. Diabetes management, public health intervention for hazardous alcohol consumption, provision of housing to address homelessness, and patient education on melioidosis prevention in First Nations languages should be prioritised.
Topics: Australia; Burkholderia pseudomallei; Humans; Melioidosis; Risk Factors
PubMed: 35696415
DOI: 10.1371/journal.pntd.0010486 -
Journal of Nephrology Dec 2021Melioidosis is a potentially fatal tropical infection caused by Burkholderia pseudomallei. Kidney involvement is possible, but has not been well described. (Observational Study)
Observational Study
BACKGROUND
Melioidosis is a potentially fatal tropical infection caused by Burkholderia pseudomallei. Kidney involvement is possible, but has not been well described.
AIM
This study aimed to assess the risk of acute kidney injury (AKI) and its outcomes in melioidosis.
METHODS
A retrospective observational cohort study was performed. Case records of consecutive patients with culture-confirmed melioidosis, observed from January 1st, 2012 through December 31st, 2019 were analysed for demographics, presence of comorbidities, including chronic kidney disease (CKD), diabetes mellitus (DM), and presence of bacteraemia, sepsis, shock, AKI, and urinary abnormalities. The outcomes we studied were: mortality, need for hospitalisation in an intensive care unit (ICU), duration of hospitalization. We then compared the outcomes between patients with and without AKI.
RESULTS
Of 164 patients, AKI was observed in 59 (35.98%), and haemodialysis was required in eight (13.56%). In the univariate analysis, AKI was associated with CKD (OR 5.83; CI 1.140-29.90, P = 0.03), bacteraemia (OR 8.82; CI 3.67-21.22, P < 0.001) and shock (OR 3.75; CI 1.63-8.65, P = 0.04). In the multivariate analysis, CKD (adjusted OR 10.68; 95% CI 1.66-68.77; P = 0.013) and bacteraemia (adjusted OR 8.22; 95% CI 3.15-21.47, P < 0.001) predicted AKI. AKI was associated with a greater need for ICU care (37.3% vs. 13.3%, P = 0.001), and mortality (32.2% vs. 5.7%, P < 0.001). Mortality increased with increasing AKI stage, i.e. stage 1 (OR 3.52, CI 0.9-13.7, P = 0.07), stage 2 (OR 6.79, CI 1.92-24, P = 0.002) and stage 3 (OR 17.8, CI 5.05-62.8, P < 0.001), however kidney function recovered in survivors. Hyponatremia was observed in 138 patients (84.15%) and isolated urinary abnormalities were seen in 31(18.9%).
CONCLUSIONS
AKI is frequent in melioidosis and occurred in 35.9% of our cases. Hyponatremia is likewise common. AKI was predicted by bacteraemia and CKD, and was associated with higher mortality and need for ICU care; however kidney function recovery was observed in survivors.
Topics: Acute Kidney Injury; Humans; Intensive Care Units; Melioidosis; Prognosis; Retrospective Studies; Risk Factors
PubMed: 33515381
DOI: 10.1007/s40620-021-00970-x