Search Results (96)

Background: Melioidosis, caused by Burkholderia pseudomallei, is a serious infectious disease in Southeast Asia and northern Australia. Methods: We systematically reviewed observational studies measuring C-reactive protein (CRP) in laboratory-confirmed melioidosis for diagnosis, severity assessment, or outcome evaluation. PubMed, Embase, and Scopus were searched up to May 2025. Data were pooled using a random-effects model; heterogeneity was quantified (I²). Results: Seven studies (n = 451) were included. The pooled mean CRP level in melioidosis was 74.37 mg/L (95% Confidence Interval [CI], 32.76–168.83; I² = 99.1%), considerably higher than healthy reference values (<10 mg/L). Conclusions: CRP is consistently raised in melioidosis and may aid in early diagnosis and severity monitoring, although high heterogeneity limits the precision of pooled estimates. Integration of CRP into multimodal prediction tools, rather than use in isolation, is recommended. Further prospective studies should define optimal diagnostic thresholds. Full article

Background: Melioidosis is a severe infectious disease caused by Burkholderia pseudomallei, with high mortality rates, particularly in severe cases complicated by acute kidney injury (AKI). Objective: The objective of this study was to systematically review and quantitatively synthesize the impact of AKI on mortality and other clinical outcomes—including ICU admission and the need for renal replacement therapy (RRT)—in patients with melioidosis. Methods: A systematic search was conducted in PubMed, Scopus, and Embase up to 16 May 2025. Studies reporting mortality, ICU admission, or RRT use in patients with AKI were included. A random-effects meta-analysis was performed to estimate the odds ratio (OR) for mortality associated with AKI. Results: Twenty-nine studies (380 patients) were included. AKI occurred in 123 patients (32.4%). The pooled analysis revealed that AKI patients had a significantly higher mortality risk than non-AKI patients (OR = 23.37; 95% CI: 13.97–39.10; p = 0.0082), with no significant heterogeneity (I² = 0%). Sensitivity analysis confirmed the robustness of this association. ICU admission and RRT data were frequently reported but were not suitable for meta-analysis due to insufficient data. Conclusions: AKI is a serious complication in melioidosis, significantly increasing the risk of mortality. Early recognition and aggressive management of AKI in melioidosis may be critical to improving clinical outcomes. Full article

Background: Burkholderia pseudomallei, the causative agent of melioidosis, is intrinsically resistant to multiple antibiotics, posing substantial challenges for treatment. Reports of acquired resistance are increasing, underscoring the need for global surveillance. Objective: This systematic review and meta-analysis aimed to determine the global prevalence of antibiotic-resistant B. pseudomallei isolated from human clinical cases, with a focus on regional differences and variations in antimicrobial susceptibility testing methods. Methods: We systematically searched PubMed, Scopus, and Embase for studies reporting resistance in clinical B. pseudomallei isolates, following PRISMA guidelines. Pooled resistance rates to 11 antibiotics were calculated using a random-effect model. Subgroup analyses were performed based on geographical region and testing methodology (MIC vs. disk diffusion). Results: Twelve studies comprising 10,391 isolates were included. Resistance rates varied across antibiotics, with the highest pooled resistance observed for tigecycline (46.3%) and ciprofloxacin (38.3%). Ceftazidime (CAZ) and trimethoprim–sulfamethoxazole (SXT), commonly used first-line agents, showed resistance rates of 5.3% and 4.2%, respectively. Subgroup analyses of CAZ and SXT revealed significantly higher resistance in studies from Asia compared to Australia and America (p value < 0.0001). Disk diffusion methods tended to overestimate resistance compared to MIC-based approaches, which revealed non-significant differences for CAZ (p value = 0.5343) but significant differences for SXT (p value < 0.0001). Conclusions: Antibiotic resistance in B. pseudomallei exhibits regional variation and is influenced by the susceptibility testing method used. Surveillance programs and standardized antimicrobial susceptibility testing protocols are essential to guide effective treatment strategies and ensure accurate resistance reporting. Full article

Burkholderia lethal factor 1 (BLF1), a toxin derived from Burkholderia pseudomallei, reacts with eukaryotic initiation factor (eIF) 4A to inhibit protein synthesis. eIF4A1 and eIF4A2 are involved in translation initiation and share over 90% sequence similarity. However, they exert distinct effects on cancer treatment outcomes. To understand the molecular mechanism by which BLF1 modulates eIF4A isoforms in cancer cells, we investigated its effects on eIF4A-mediated adenosine 5′-triphosphate (ATP) hydrolysis. We found that eIF4A1 has a higher ATP-binding affinity compared to eIF4A2 (K_m = 6.55 ± 0.78 μM vs. K_m = 11.61 ± 2.33 μM). Meanwhile, we also found that eIF4A1 is more sensitive to changes in temperature, pH, and Mg²⁺ concentration. Through N-terminal swapping and single amino acid mutations, we found that leucine 98 (L98) and alanine 100 (A100) play important roles in the ATPase activities of eIF4A isoforms. Moreover, BLF1 treatment significantly enhanced eIF4A2-mediated ATP hydrolysis at all tested ATP concentrations. These differences in BLF1-regulated eIF4A isoforms may explain its selective cytotoxicity against cancer cells. Our findings provide molecular insights into the functional difference between eIF4A isoforms and suggest that BLF1 might be of promising value for anticancer therapies. Full article

Melioidosis, caused by Burkholderia pseudomallei, is a potentially fatal infection, particularly affecting individuals with chronic conditions such as diabetes or kidney or liver diseases. This review examines melioidosis in India over the past two decades, focusing on its prevalence, risk factors and clinical manifestations. A PubMed search (2000–2024) identified a rise in melioidosis publications, with most from Southern India, followed by Eastern India, and an increase post-2019. Eight studies from 2010–2022 identified fever (86%), cough (26%) and joint pain (23%) as the most common symptoms, while diabetes (75%), alcohol abuse (19%) and cancer (6%) were primary predisposing factors. Severe clinical manifestations were also observed, including bacteremia (50%), pneumonia (37%) and splenic abscess (18%). Although environmental exposure risks were not significantly high, individuals with diabetes or chronic kidney disease, particularly those working in high-risk environments, were more likely to contract melioidosis. Cryptic environmental factors that might bridge known epidemiological risk factors are also addressed. The review emphasizes the increasing awareness and research in clinical epidemiology and also highlights a gap in studies on antimicrobial treatments, vaccines and environmental surveillance. Targeted interventions in diabetes and poverty hotspots could help control the disease more effectively. Full article

Melioidosis is an endemic tropical disease caused by Burkholderia pseudomallei. It typically causes pulmonary disease and bacteraemia but can disseminate to cause multi-organ disease. 18-F FDG PET/CT has an evolving role in diagnosing other infectious diseases, especially where the pathogen or extent of infection is challenging to elucidate clinically and with conventional imaging (CT, US and MRI). We present a case series of patients diagnosed with melioidosis who also underwent 18-F FDG PET/CT from December 18th 2018 to September 30th 2022. Indications for imaging were categorised and analysed as to whether 18-F FDG PET/CT changed management over conventional imaging. Twenty-one 18-F FDG PET/CT scans were performed for sixteen patients. Two scans (9.5%) performed for pyrexia of unknown origin changed management in both cases. Twelve scans (57.1%) performed to ascertain the extent of dissemination of melioidosis changed management in only three (25%) cases. Five scans (23.8%) performed to monitor the response to treatment of known foci changed management in all five cases. Five scans (23.8%) performed for suspected or known malignancy changed management in three (60%) cases. 18-F FDG PET/CT is an emerging tool which improves diagnosis and changes the management of melioidosis when applied judiciously and for well-selected indications. Full article

Melioidosis, an infection with the bacterium Burkholderia pseudomallei, is highly endemic in the Top End of the Northern Territory of Australia. The indirect haemagglutination assay (IHA) is the most widely used serology test globally, but it is not standardised among the limited number of laboratories that perform it. While concerns have been raised about the sensitivity of IHA early in melioidosis infections, the advantage of IHA over more recently developed ELISAs is that testing serial dilutions allows a titre to be recorded. While in Australia a titre of 1:40 or higher is considered positive, the specificity at these low positive titres remains uncertain. However, a high titre is considered to represent recent or past true infection with B. pseudomallei, rather than cross-rection with other environmental Burkholderia species. Also, the natural history of IHA titres over time, in both asymptomatic infection and melioidosis has been little studied. We have assessed the clinical status and serology time courses of all 534 patients who had an IHA titre of 1:640 or higher, over a 20-year period. Of these, 324 (60.7%) were diagnosed with culture-confirmed melioidosis, with varying time courses of diagnosis of melioidosis in relation to the high serology. Of the 210 without confirmed melioidosis, 22 (10.5%) were considered highly likely to be melioidosis despite being culture-negative, and these were all treated as melioidosis. In the remainder, titres mostly gradually decreased over time, but the majority remained seropositive. A small number who had not been treated for melioidosis continued to have high IHA titres over years and activation from latency with a new diagnosis of melioidosis was occasionally documented. This study highlights the importance of a full clinical workup in those found to have high titre melioidosis serology as well as subsequent close clinical surveillance and where resources allow, yearly IHA in those not confirmed or treated as melioidosis. Full article

Melioidosis is a zoonotic disease that is caused by Burkholderia pseudomallei, which is a serious public health and safety risk. In order to explore the global animal melioidosis risk distribution and its dynamic response to future climate scenarios, we collected global data about reported animal incidence sites. Data regarding the density of Burkholderia pseudomallei in the environment were created by collecting and sorting information about the Burkholderia pseudomallei occurrence sites in contaminated air, soil, and water. Combined with bioclimatic variables, the maximum entropy (MaxEnt) niche was modeled for global animal melioidosis. The findings indicate that under current bioclimatic conditions, global animal melioidosis risk regions are concentrated between 30° S and 30° N, with high-risk areas being mainly in Central America, the northern part of South America, and eastern and southern India, among others. Most countries will expand their risk regions under future climatic scenarios. Melioidosis risk expanding towards higher northern latitudes has led to new epidemic areas. In addition, the melioidosis risk area will contract in some areas. Therefore, we have provided a basis for global melioidosis surveillance and propose feasible strategies for prevention and control in high-risk regions, which will help countries to carry out targeted surveillance and prevention to reduce risks and losses. Full article

Introduction: Patients receiving biological and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) for rheumatological conditions are at an increased risk of serious, potentially life-threatening, infection. However, the incidence, aetiology, and clinical course of serious infection in patients receiving b/tsDMARDs in tropical settings are incompletely defined. Methods: We retrospectively reviewed all patients with rheumatoid arthritis receiving b/tsDMARDs between October 2012 and October 2021, at Cairns Hospital in tropical Australia. The incidence, aetiology, and clinical course of serious infections (those requiring admission to hospital or parenteral antibiotics) were determined. Results: 310 patients had 1468 patient years of b/tsDMARD therapy during the study period; 74/310 (24%) had 147 serious infections translating to an overall risk of 10.0 episodes of serious infection per 100 patient years. The respiratory tract (50/147, 34%) and skin (37/147, 25%) were the most frequently affected sites. A pathogen was identified in 59/147 (40%) episodes and was most commonly Staphylococcus aureus (24/147, 16%). Only 2/147 (1%) were confirmed “tropical infections”: 1 case of Burkholderia pseudomallei and 1 case of mixed B. pseudomallei and community-acquired Acinetobacter baumannii infection. Overall, 13/147 (9%) episodes of serious infection required Intensive Care Unit admission (0.9 per 100-patient years of b/tsDMARD therapy) and 4/147 (3%) died from their infection (0.3 per 100-patient years of b/tsDMARD therapy). The burden of comorbidity and co-administration of prednisone were the strongest predictors of death or a requirement for ICU admission. Conclusions: The risk of serious infection in patients taking b/tsDMARDs in tropical Australia is higher than in temperate settings, but this is not explained by an increased incidence of traditional tropical pathogens. Full article

Endemic in over 45 countries globally, recent reports of locally acquired melioidosis in novel geographical areas, such as the Southern US, have highlighted the expanding geographical range of Burkholderia pseudomallei. Climate change and severe weather events have been linked to an increase in cases of melioidosis, which follows environmental exposure to the bacterium. Healthcare professionals should be aware of the possibility of the disease, with its diverse and often delayed presentations, even in areas not previously known to have risk. Over 200 cases of travel-associated melioidosis have been reported in the literature, highlighting the need to consider this disease in non-endemic areas, as diagnostic delays of up to 18 months have been identified. The review updates the global epidemiology of melioidosis, focusing on new geographical areas where cases have been diagnosed and imported cases, unusual clinical presentations and co-infections, and less frequent modes of transmission (laboratory exposures and the risk of acquisition due to imported infected animals and contaminated products). Full article

Background: Burkholderia pseudomallei, the causative agent of melioidosis, is highly genetically recombinant, resulting in significant genomic diversity. Multiple virulence factors have been associated with specific disease presentations. To date, there are limited data relating to genomic diversity and virulence factors associated with melioidosis cases in North Queensland, Australia. Aim: To describe the genetic diversity of B. pseudomallei and identify virulence factors associated with clinical risk factors and patient outcomes. Methods: Whole genome sequencing of clinical isolates was performed and analysed with clinical data obtained from a retrospective melioidosis cohort study. Results: Fifty-nine distinct sequence types (STs) were identified from the 128 clinical isolates. Six STs comprised 64/128 (50%) isolates. Novel STs accounted for 38/59 (64%) STs, with ST TSV-13 as the most prevalent (n = 7), and were less likely to possess an LPS A genotype or YLF gene cluster (p < 0.001). These isolates were most likely to be found outside the inner city (aOR: 4.0, 95% CI: 1.7–9.0, p = 0.001). ST TSV-13 was associated with increased mortality (aOR: 6.1, 95% CI: 1.2–30.9, p = 0.03). Patients with a history of alcohol excess were less likely to be infected by fhaB3 (aOR 0.2, 95% CI: 0.1–0.7, p = 0.01) or YLF (aOR: 0.4, 95% CI: 0.2–0.9, p = 0.04) positive isolates. Conclusions: There are a significant number of novel sequence types in Townsville, Australia. An emerging novel ST appears to have an association with geographic location and mortality. Ongoing investigation is required to further understand the impact of this ST on the Townsville region. Full article

Background: Melioidosis, a disease induced by Burkholderia pseudomallei, poses a significant health threat in tropical areas where it is endemic. Despite the availability of effective treatments, mortality rates remain notably elevated. Many risk factors are associated with mortality. This study aims to develop a scoring system for predicting the in-hospital mortality from melioidosis using readily available clinical data. Methods: The data were collected from Surin Hospital, Surin, Thailand, during the period from April 2014 to March 2017. We included patients aged 15 years and above who had cultures that tested positive for Burkholderia pseudomallei. The clinical prediction rules were developed using significant risk factors from the multivariable analysis. Results: A total of 282 patients with melioidosis were included in this study. In the final analysis model, 251 patients were used for identifying the significant risk factors of in-hospital fatal melioidosis. Five factors were identified and used for developing the clinical prediction rules, and the factors were as follows: qSOFA ≥ 2 (odds ratio [OR] = 2.39, p= 0.025), abnormal chest X-ray findings (OR = 5.86, p < 0.001), creatinine ≥ 1.5 mg/dL (OR = 2.80, p = 0.004), aspartate aminotransferase ≥50 U/L (OR = 4.032, p < 0.001), and bicarbonate ≤ 20 mEq/L (OR = 2.96, p = 0.002). The prediction scores ranged from 0 to 7. Patients with high scores (4–7) exhibited a significantly elevated mortality rate exceeding 65.0% (likelihood ratio [LR+] 2.18, p < 0.001) compared to the low-risk group (scores 0–3) with a lower mortality rate (LR + 0.18, p < 0.001). The area under the receiver operating characteristic curve (AUC) was 0.84, indicating good model performance. Conclusions: This study presents a simple scoring system based on easily obtainable clinical parameters to predict in-hospital mortality in melioidosis patients. This tool may facilitate the early identification of high-risk patients who could benefit from more aggressive treatment strategies, potentially improving clinical decision-making and patient outcomes. Full article

Early diagnosis is essential for the successful management of Burkholderia pseudomallei infection, but it cannot be achieved by the current gold standard culture technique. Therefore, this study aimed to develop a lateral flow immunoassay (LFIA) targeting B. pseudomallei capsular polysaccharide. The development was performed by varying nitrocellulose membrane reaction pads and chase buffers. The prototype LFIA is composed of Unisart CN95 and chase buffer containing tris-base, casein, and Surfactant 10G. The assay showed no cross-reactivity with E. coli, S. aureus, P. aeruginosa, and P. acne. The limit of detections (LODs) of the prototype LFIA was 10⁷ and 10⁶ CFU/mL B. pseudomallei in hemoculture medium and artificial urine, respectively. These LODs suggest that this prototype can detect melioidosis from positive hemoculture bottles but not straight from urine. Additionally, these LODs are still inferior compared to Active Melioidosis Detect (AMD^TM). Overall, this prototype holds the potential to be used clinically with hemoculture bottles. However, further improvements should be considered, especially for use with urine samples. Full article

Melioidosis is an endemic infectious disease caused by Burkholderia pseudomallei bacteria, which contaminates soil and water. To better understand the environmental changes that have contributed to melioidosis outbreaks, this study used spatiotemporal analyses to clarify the distribution pattern of melioidosis and the relationship between melioidosis morbidity rate and local environmental indicators (land surface temperature, normalised difference vegetation index, normalised difference water index) and rainfall. A retrospective study was conducted from January 2013 to December 2022, covering data from 219 sub-districts in Northeast Thailand, with each exhibiting a varying morbidity rate of melioidosis on a monthly basis. Spatial autocorrelation was determined using local Moran’s I, and the relationship between the melioidosis morbidity rate and the environmental indicators was evaluated using a geographically weighted Poisson regression. The results revealed clustered spatiotemporal patterns of melioidosis morbidity rate across sub-districts, with hotspots predominantly observed in the northern region. Furthermore, we observed a range of coefficients for the environmental indicators, varying from negative to positive, which provided insights into their relative contributions to melioidosis in each local area and month. These findings highlight the presence of spatial heterogeneity driven by environmental indicators and underscore the importance of public health offices implementing targeted monitoring and surveillance strategies for melioidosis in different locations. Full article

In contrast to “frank” pathogens, like Salmonella entrocolitica, Shigella dysenteriae, and Vibrio cholerae, that always have a probability of disease, “opportunistic” pathogens are organisms that cause an infectious disease in a host with a weakened immune system and rarely in a healthy host. Historically, drinking water treatment has focused on control of frank pathogens, particularly those from human or animal sources (like Giardia lamblia, Cryptosporidium parvum, or Hepatitis A virus), but in recent years outbreaks from drinking water have increasingly been due to opportunistic pathogens. Characteristics of opportunistic pathogens that make them problematic for water treatment include: (1) they are normally present in aquatic environments, (2) they grow in biofilms that protect the bacteria from disinfectants, and (3) under appropriate conditions in drinking water systems (e.g., warm water, stagnation, low disinfectant levels, etc.), these bacteria can amplify to levels that can pose a public health risk. The three most common opportunistic pathogens in drinking water systems are Legionella pneumophila, Mycobacterium avium, and Pseudomonas aeruginosa. This report focuses on these organisms to provide information on their public health risk, occurrence in drinking water systems, susceptibility to various disinfectants, and other operational practices (like flushing and cleaning of pipes and storage tanks). In addition, information is provided on a group of nine other opportunistic pathogens that are less commonly found in drinking water systems, including Aeromonas hydrophila, Klebsiella pneumoniae, Serratia marcescens, Burkholderia pseudomallei, Acinetobacter baumannii, Stenotrophomonas maltophilia, Arcobacter butzleri, and several free-living amoebae including Naegleria fowleri and species of Acanthamoeba. The public health risk for these microbes in drinking water is still unclear, but in most cases, efforts to manage Legionella, mycobacteria, and Pseudomonas risks will also be effective for these other opportunistic pathogens. The approach to managing opportunistic pathogens in drinking water supplies focuses on controlling the growth of these organisms. Many of these microbes are normal inhabitants in biofilms in water, so the attention is less on eliminating these organisms from entering the system and more on managing their occurrence and concentrations in the pipe network. With anticipated warming trends associated with climate change, the factors that drive the growth of opportunistic pathogens in drinking water systems will likely increase. It is important, therefore, to evaluate treatment barriers and management activities for control of opportunistic pathogen risks. Controls for primary treatment, particularly for turbidity management and disinfection, should be reviewed to ensure adequacy for opportunistic pathogen control. However, the major focus for the utility’s opportunistic pathogen risk reduction plan is the management of biological activity and biofilms in the distribution system. Factors that influence the growth of microbes (primarily in biofilms) in the distribution system include, temperature, disinfectant type and concentration, nutrient levels (measured as AOC or BDOC), stagnation, flushing of pipes and cleaning of storage tank sediments, and corrosion control. Pressure management and distribution system integrity are also important to the microbial quality of water but are related more to the intrusion of contaminants into the distribution system rather than directly related to microbial growth. Summarizing the identified risk from drinking water, the availability and quality of disinfection data for treatment, and guidelines or standards for control showed that adequate information is best available for management of L. pneumophila. For L. pneumophila, the risk for this organism has been clearly established from drinking water, cases have increased worldwide, and it is one of the most identified causes of drinking water outbreaks. Water management best practices (e.g., maintenance of a disinfectant residual throughout the distribution system, flushing and cleaning of sediments in pipelines and storage tanks, among others) have been shown to be effective for control of L. pneumophila in water supplies. In addition, there are well documented management guidelines available for the control of the organism in drinking water distribution systems. By comparison, management of risks for Mycobacteria from water are less clear than for L. pneumophila. Treatment of M. avium is difficult due to its resistance to disinfection, the tendency to form clumps, and attachment to surfaces in biofilms. Additionally, there are no guidelines for management of M. avium in drinking water, and one risk assessment study suggested a low risk of infection. The role of tap water in the transmission of the other opportunistic pathogens is less clear and, in many cases, actions to manage L. pneumophila (e.g., maintenance of a disinfectant residual, flushing, cleaning of storage tanks, etc.) will also be beneficial in helping to manage these organisms as well. Full article