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PURPOSE OF REVIEW: Melioidosis, caused by the soil-dwelling bacterium Burkholderia pseudomallei, is a tropical infection associated with high morbidity and mortality. This review summarizes current insights into melioidosis' endemicity, focusing on epidemiological transitions, zoonosis, and climate change. RECENT FINDINGS: Estimates of the global burden of melioidosis affirm the significance of hot-spots in Australia and Thailand. However, it also highlights the paucity of systematic data from South Asia, The Americas, and Africa. Globally, the growing incidence of diabetes, chronic renal and (alcoholic) liver diseases further increase the susceptibility of individuals to B. pseudomallei infection. Recent outbreaks in nonendemic regions have further exposed the hazard from the trade of animals and products as potential reservoirs for B. pseudomallei. Lastly, global warming will increase precipitation, severe weather events, soil salinity and anthrosol, all associated with the occurrence of B. pseudomallei. SUMMARY: Epidemiological transitions, zoonotic hazards, and climate change are all contributing to the emergence of novel melioidosis-endemic areas. The adoption of the One Health approach involving multidisciplinary collaboration is important in unraveling the real incidence of B. pseudomallei, as well as reducing the spread and associated mortality.

This study investigates whether resistance-associated mutations develop after treatment with sotrovimab in high-risk patients infected with the SARS-CoV-2 Omicron variant.

There is an error in the article XML causing the eighth author’s name to be indexed incorrectly. The name should be indexed as van der Poll T.

Thrombocytopenia predicts mortality in melioidosis patients and during experimental melioidosis, platelets play a protective role in both innate immunity and vascular integrity., Background Infection with the gram-negative bacillus Burkholderia pseudomallei (melioidosis) is an important cause of pneumosepsis in Southeast Asia and has a mortality of up to 40%. We aimed to assess the role of platelets in the host response against B. pseudomallei infection. Methods Association between platelet counts and mortality was determined in 1160 patients with culture-proven melioidosis. Mice treated with (low- or high-dose) platelet-depleting antibody were inoculated intranasally with B. pseudomallei and killed. Additional studies using functional glycoprotein Ibα–deficient mice were conducted. Results Thrombocytopenia was present in 31% of patients at admission and predicted mortality in melioidosis patients even after adjustment for confounders. In our murine-melioidosis model, platelet counts decreased, and mice treated with a platelet-depleting antibody showed enhanced mortality and higher bacterial loads compared to mice with normal platelet counts. Low platelet counts had a modest impact on early-pulmonary neutrophil influx. Reminiscent of their role in hemostasis, platelet depletion impaired vascular integrity, resulting in early lung bleeding. Glycoprotein Ibα–deficient mice had reduced platelet counts during B. pseudomallei infection together with an impaired local host defense in the lung. Conclusions Thrombocytopenia predicts mortality in melioidosis patients and, during experimental melioidosis, platelets play a protective role in both innate immunity and vascular integrity.

Background: Melioidosis, caused by the Gram-negative bacterium Burkholderia pseudomallei, is an opportunistic infection across the tropics. Here, we provide a systematic overview of imported human cases in a non-endemic country over a 25-year period. Methods: All 55 Dutch microbiology laboratories were contacted in order to identify all B. pseudomallei positive cultures from 1990 to 2018. A response rate of 100% was achieved. Additionally, a systematic literature search was performed, medical-charts reviewed, and tissue/autopsy specimens were re-assessed. Results: Thirty-three travelers with melioidosis were identified: 70% male with a median-age of 54 years. Risk factors were present in most patients (n = 23, 70%), most notably diabetes (n = 8, 24%) and cystic fibrosis (n = 3, 9%). Countries of acquisition included Thailand, Brazil, Indonesia, Panama, and The Gambia. Disease manifestations included pneumonia, intra-abdominal abscesses, otitis externa, genitourinary, skin-, CNS-, and thyroid gland infections. Twelve (36%) patients developed sepsis and/or septic shock. Repeat episodes of active infection were observed in five (15%) and mortality in four (12%) patients. Post-mortem analysis showed extensive metastatic (micro)abscesses amongst other sites in the adrenal gland and bone marrow. Conclusions: The number of imported melioidosis is likely to increase, given rising numbers of (immunocompromised) travelers, and increased vigilance of the condition. This first systematic retrospective surveillance study in a non-endemic melioidosis country shows that imported cases can serve as sentinels to provide information about disease activity in areas visited and inform pre-travel advice and post-travel clinical management.

To ensure safe and efficient operations, all offshore operations follow a plan devised to take into account current operation conditions and identify the optimum workflow with the minimum risk potential. Previously, planners had to manually consult eight data sources, each with a separate UI, and summarise the plan in a.pdf document. Equinor's Operation Planning Tool (OPT) has been developed to easily present the planners with the technical conditions of a platform, identify potentially dangerous combinations of concurrent activities, and propose learnings from eight years’ worth of incident recordings – all relevant to the current list of planned activities. The tool aims to answer questions such as ‘are other activities planned for the same time which would make this activity unsafe?’ or ‘have incidents previously occurred whilst performing similar tasks on this equipment type?’. This paper details the development of the OPT with a particular focus on the application of Natural Language Understanding for extracting equipment types and tasks involved in previous incidents and relating these to planned activities. Utilising natural language processing techniques, a system has been developed that mines the content of Equinor's incident database, and assigns context to incidents, by identifying the systems, activities and equipment involved and the conditions on the asset at the time of the incident. The same context is also discovered from the content of planned activities. These key concepts are organised into a knowledge graph synthesising Equinor's institutional safety and operational experience. The OPT has reduced time spent planning by providing a single interface detailing a plant's technical conditions, all planned work orders and relevant lessons learned from previous incidents. By reducing the reliance on personal experience, the tool has provided subjectively improved risk identification and handling, plus faster knowledge transfer to new employees as well as focussed cross-platform knowledge sharing. The success of the tool highlights the strength of combining data and leveraging the vast quantities of historic data available both in unstructured and structured forms to create a safe, offshore work environment.

The Gram-negative intracellular pathogen Burkholderia pseudomallei is the causative agent of melioidosis, an important cause of sepsis in Southeast Asia. Recognition of pathogen-associated molecular patterns by Toll-like receptors (TLRs) is essential for an appropriate immune response during pathogen invasion. In patients with melioidosis, TLR5 is the most abundantly expressed TLR, and a hypofunctional TLR5 variant has been associated with improved survival. Here, we studied the functional role of TLR5 and its ligand flagellin in experimental melioidosis. First, we observed differential TLR5 expression in the pulmonary and hepatic compartments upon infection with B. pseudomallei. Next, we found that B. pseudomallei-challenged TLR5-deficient (Tlr5(−/−)) mice were more susceptible to infection than wild-type (WT) mice, as demonstrated by higher systemic bacterial loads, increased organ injury, and impaired survival. Lung bacterial loads were not different between the two groups. The phenotype was flagellin independent; no difference in in vivo virulence was observed for the flagellin-lacking mutant MM36 compared to the wild-type B. pseudomallei strain 1026b. Tlr5(−/−) mice showed a similar impaired antibacterial defense when infected with MM36 or 1026b. Ex vivo experiments showed that TLR5-deficient macrophages display markedly impaired phagocytosis of B. pseudomallei. In conclusion, these data suggest that TLR5 deficiency has a detrimental flagellin-independent effect on the host response against pulmonary B. pseudomallei infection.

Background: Melioidosis is an infectious disease caused by the environmental bacterium Burkholderia pseudomallei. It is often fatal, with a high prevalence in tropical areas. Clinical presentation can vary from abscess formation to pneumonia and sepsis. We assessed the global burden of melioidosis, expressed in disability-adjusted life-years (DALYs), for 2015. Methods: We did a systematic review of the peer-reviewed literature for human melioidosis cases between Jan 1, 1990, and Dec 31, 2015. Quantitative data for cases of melioidosis were extracted, including mortality, age, sex, infectious and post-infectious sequelae, antibiotic treatment, and symptom duration. These data were combined with established disability weights and expert panel discussions to construct an incidence-based disease model. The disease model was integrated with established global incidence and mortality estimates to calculate global melioidosis DALYs. The study is registered with PROSPERO, number CRD42018106372. Findings: 2888 articles were screened, of which 475 eligible studies containing quantitative data were retained. Pneumonia, intra-abdominal abscess, and sepsis were the most common outcomes, with pneumonia occurring in 3633 (35·7%, 95% uncertainty interval [UI] 34·8–36·6) of 10 175 patients, intra-abdominal abscess in 1619 (18·3%, 17·5–19·1) of 8830 patients, and sepsis in 1526 (18·0%, 17·2–18·8) of 8469 patients. We estimate that in 2015, the global burden of melioidosis was 4·6 million DALYs (UI 3·2–6·6) or 84·3 per 100 000 people (57·5–120·0). Years of life lost accounted for 98·9% (UI 97·7–99·5) of the total DALYs, and years lived with disability accounted for 1·1% (0·5–2·3). Interpretation: Melioidosis causes a larger disease burden than many other tropical diseases that are recognised as neglected, and so it should be reconsidered as a major neglected tropical disease. Funding: European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Research Grant 2018, AMC PhD Scholarship, The Netherlands Organisation for Scientific Research (NWO), H2020 Marie Skłodowska-Curie Innovative Training Network European Sepsis Academy.

ABSTRACT Melioidosis is a life-threatening infection caused by the Gram-negative bacterium Burkholderia pseudomallei, mainly found in Southeast Asia. Recently, African foci have been identified, although reports remain mostly anecdotal. In Africa, multiple febrile diseases have been erroneously attributed to malaria in the past, and many cases of fever remain mis- or undiagnosed. Vigilance for previously under-recognized pathogens may enhance our understanding of disease epidemiology and facilitate improvement of patient care. Melioidosis may be such a condition. We summarize data on melioidosis in Africa and discuss the future directions for epidemiological, clinical and bacteriological studies. We conclude that searching for old bugs in new places is no academic treasure hunt but a clinically relevant activity to pursue.

Melioidosis is a severe infectious disease with a high mortality that is endemic in South-East Asia and Northern Australia. The causative pathogen, Burkholderia pseudomallei, is listed as potential bioterror weapon due to its high virulence and potential for easy dissemination. Currently, there is no licensed vaccine for prevention of melioidosis. Here, we explore the use of rapid plasmid DNA vaccination against B. pseudomallei flagellin for protection against respiratory challenge. We tested three flagellin DNA vaccines with different subcellular targeting designs. C57BL/6 mice were vaccinated via skin tattoo on day 0, 3 and 6 before intranasal challenge with B. pseudomallei on day 21. Next, the most effective construct was used as single vaccination on day 0 by tattoo or intranasal formulation. Mice were sacrificed 72 hours post-challenge to assess bacterial loads, cytokine responses, inflammation and microscopic lesions. A construct encoding a cellular secretion signal resulted in the most effective protection against melioidosis via tattooing, with a 10-fold reduction in bacterial loads in lungs and distant organs compared to the empty vector. Strikingly, a single intranasal administration of the same vaccine resulted in >1000-fold lower bacterial loads and increased survival. Pro-inflammatory cytokine responses were significantly diminished and strong reductions in markers for distant organ damage were observed. A rapid vaccination scheme using flagellin DNA tattoo provides significant protection against intranasal challenge with B. pseudomallei, markedly improved by a single administration via airway mucosa. Hence intranasal vaccination with flagellin-encoding DNA may be applicable when acute mass vaccination is indicated and warrants further testing.

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, Author summary Melioidosis, caused by bioterror threat agent Burkholderia pseudomallei, is an important cause of community-acquired sepsis in Southeast Asia and Northern Australia. Recently, it has been predicted that the annual burden of melioidosis is much higher than previously thought, with 165.000 human cases from which 89.000 patients die worldwide. Melioidosis has a mortality up to 40% despite appropriate antibiotic treatment and there is currently no vaccine available. Therefore, it is of importance to better understand the pathogenesis of this debilitating disease. There is extensive cross talk between the innate immune system and blood coagulation, which contributes to the host defense against invading bacteria. One of the hallmark features of melioidosis is extensive abnormalities in the coagulation system. Therefore, we hypothesized that, since endothelial stimulation by endotoxin, pro-inflammatory cytokines and thrombin all occur in melioidosis, these would result in derangements of Von Willebrand factor (a protein involved in hemostasis and platelet aggregation). In a cohort of culture-confirmed patients with severe melioidosis, we found that thrombocytopenia is a key feature of melioidosis and is correlated with mortality. Additionally, our study showed that excess VWF and ADAMTS13 deficiency are features of acute melioidosis, but are not the primary drivers of thrombocytopenia in melioidosis.

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Background Tuberculosis (TB) remains a major health problem in Zambia, despite considerable efforts to control and prevent it. With this study, we aim to understand how perceptions and cultural, social, economic, and organisational factors influence TB patients’ pre-hospital delay and non-compliance with care provided by the National Tuberculosis Programme (NTP). Methods A mixed methods study was conducted with 300 TB patients recruited at Kanyama clinic for structured interviews. Thirty were followed-up for multiple in-depth interviews. Six focus group discussions were organised and participant observation was conducted. Ten biomedical care providers, 10 traditional healers, and 10 faith healers were interviewed. Factors associated with non-compliance (disruption of treatment > one week) were assessed by applying logistic regression analyses; qualitative analysis was used to additionally assess factors influencing pre-hospital delay and for triangulation of study findings. Results TB treatment non-compliance was low (10 %), no association of outcome with cultural or socio-economic factors was found. Only patients’ time constraints and long distance to the clinic indicated a possible association with a higher risk of non-compliance (OR 0.52; 95 % CI 0.25, 1.10, p = 0.086). Qualitative data showed that most TB patients combined understandings of biomedical and traditional TB knowledge, used herbal, traditional and/or faith healing, suffered from stigmatizing attitudes, experienced poverty and food shortages, and faced several organisational obstacles while being on treatment. This led in some cases to pre-hospital delay or treatment non-compliance. Conclusions Mixed methods analysis demonstrated the importance of in-depth information ascertained by qualitative approaches to understand how cultural, socio-economic and organisational factors are influencing patients’ pre-hospital delay and treatment compliance. To strengthen the Zambian NTP, combating stigma is of utmost priority coupled with programmes addressing poverty. Organisational barriers and co-operation between (private) clinics and traditional/faith healers should be considered. Electronic supplementary material The online version of this article (doi:10.1186/s12889-016-3771-9) contains supplementary material, which is available to authorized users.