Effectiveness of a multifaceted prevention programme for melioidosis in diabetics (PREMEL): A stepped-wedge cluster-randomised controlled trial

BACKGROUND: Melioidosis, an often-fatal infectious disease caused by the environmental Gram-negative bacillus Burkholderia pseudomallei, is endemic in tropical countries. Diabetes mellitus and environmental exposure are important risk factors for melioidosis acquisition. We aim to evaluate the effectiveness of a multifaceted prevention programme for melioidosis in diabetics in northeast Thailand. METHODOLOGY/PRINCIPAL FINDINGS: From April 2014 to December 2018, we conducted a stepped-wedge cluster-randomized controlled behaviour change trial in 116 primary care units (PCUs) in Ubon Ratchathani province, northeast Thailand. The intervention was a behavioural support group session to help diabetic patients adopt recommended behaviours, including wearing rubber boots and drinking boiled water. We randomly allocated the PCUs to receive the intervention starting in March 2016, 2017 and 2018. All diabetic patients were contacted by phone yearly, and the final follow-up was December 2018. Two primary outcomes were hospital admissions involving infectious diseases and culture-confirmed melioidosis. Of 9,056 diabetics enrolled, 6,544 (72%) received a behavioural support group session. During 38,457 person-years of follow-up, we observed 2,195 (24%) patients having 3,335 hospital admissions involved infectious diseases, 80 (0.8%) melioidosis, and 485 (5%) deaths. In the intention-to-treat analysis, implementation of the intervention was not associated with primary outcomes. In the per-protocol analysis, patients who received a behavioural support group session had lower incidence rates of hospital admissions involving infectious diseases (incidence rate ratio [IRR] 0.89; 95%CI 0.80-0.99, p = 0.03) and of all-cause mortality (IRR 0.54; 95%CI 0.43-0.68, p<0.001). However, the incidence rate of culture-confirmed melioidosis was not significantly lower (IRR 0.96, 95%CI 0.46-1.99, p = 0.66). CONCLUSIONS/SIGNIFICANCE: Clear benefits of this multifaceted prevention programme for melioidosis were not observed. More compelling invitations for the intervention, modification of or addition to the behaviour change techniques used, and more frequent intervention may be needed. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov, number NCT02089152

[Epidemiology of oral cavity cancers in France].

INTRODUCTION: We had for objective to describe the updated epidemiology of oral cancers in France. MATERIAL AND METHODS: Estimates made from data collected from various French cancer institutions. The distribution by topography, histology, regions, mean age, and specific incidence rates were calculated from the collected data. The survival data was taken from the Francim network studies. RESULTS: Approximately 7000 oral cavity cancers were diagnosed in France in 2005. In 2007, 1746 people died of that cancer. Standardized (world population) incidence rates are respectively, in men and women, 12.3 and 3.0 cases per 100,000 person-years. These cancers have significantly decreased in men: the standardized incidence rate decreased by 43.2% between 1980 and 2005. Among women, the trend is reversed with an increased incidence of 51.7% over the same period. CONCLUSION: In France, the incidence of oral cavity cancers has been strongly decreasing in men and strongly increasing in women. This trend should be compared to the frequency of the main risk factors: alcohol and tobacco

Feasibility and initial outcomes of a multifaceted prevention programme of melioidosis in diabetic patients in Ubon Ratchathani, northeast Thailand

Background: Melioidosis is an infection caused by Burkholderia pseudomallei, a Gram-negative bacillus found in soil and water. Diabetes mellitus is the most important risk factor for melioidosis. The recommendations for disease prevention include avoiding direct contact with soil and water, and drinking only boiled or bottled water. Methods: A prospective intervention study was conducted to evaluate the feasibility and behavioural outcomes of a multifaceted prevention programme for melioidosis. Participants were diabetic adults in Ubon Ratchathani, northeast Thailand. Ten behavioural support groups consisting of 6 to 10 participants per group were conducted. Twelve behaviour change techniques were used: information about health consequences, credible source, adding objects to the environment, reconstructing the physical environment, instruction on how to perform a behaviour, demonstration of the behaviour, commitment, prompts/cues, self-monitoring of behaviour, goal setting, feedback on behaviour, and social support, and their feasibilities evaluated. Results: There were 70 participants, of median age 59 years and 52 (74%) were female. Participants found the intervention beneficial, interesting and engaging. Participants indicated that they liked to watch videos with information about melioidosis delivered by local doctors and patients who survived melioidosis, and videos showing use of over-the-knee boots by local farmers. Participants felt engaged in the sessions that trialed protective gear and that made calendars with individual photographs and self-pledges as a reminder tool. The proportions of participants reporting that they always wore boots while working in rice fields increased from 30% (10/33) to 77% (28/37, p = 0.04), and that they drank only boiled or bottle water increased from 43% (30/70) to 86% (59/69, p<0.001) at 6 months post intervention. Conclusion: The programme is highly acceptable to participants, and can support behaviour change. Policy makers should consider implementing the programme in areas where melioidosis is endemic. Making calendars with individual photographs and self-pledges as a reminder tool could be powerful in behaviour change interventions, and further research on this component is needed. Author summary: Melioidosis is a serious infectious disease caused by the Gram-negative environmental bacterium, Burkholderia pseudomallei. Infection in humans occurs following skin inoculation, inhalation or ingestion. The recommendations for melioidosis prevention include using protective gear such as rubber boots when in direct contact with soil and environmental water, and drinking only boiled or bottled water. A multifaceted prevention programme is recommended to achieve the desired behaviour changes. Here, we evaluated the feasibility and behavioural outcomes of a multifaceted prevention programme for melioidosis. Our study participants were diabetic adults in Ubon Ratchathani, northeast Thailand. We found that the multifaceted prevention programme was highly acceptable to participants, and could support behaviour change. A calendar with an individual photograph as a reminder tool engaged participants effectively. Our study also confirmed that commitment and action by the government are essential for the preventive interventions to be successful. We recommend that policy makers should consider implementing the programme in areas where melioidosis is endemic. Since cultures and barriers to adopting the recommended behaviours vary, the intervention strategies would need to be adapted to local contexts

Adjunctive granulocyte colony-stimulating factor for treatment of septic shock due to melioidosis

1427 E 60TH ST, CHICAGO, USA, IL, 60637-295

Glyburide Is Anti-inflammatory and Associated with Reduced Mortality in Melioidosis

Patients with diabetes have better survival from septic melioidosis than patients who without diabetes. This difference was seen only in patients taking glyburide prior to presentation and was associated with an anti-inflammatory effect of glyburide

In vitro antimicrobial activity of natural toxins and animal venoms tested against Burkholderia pseudomallei

BACKGROUND: Burkholderia pseudomallei are the causative agent of melioidosis. Increasing resistance of the disease to antibiotics is a severe problem in treatment regime and has led to intensification of the search for new drugs. Antimicrobial peptides are the most ubiquitous in nature as part of the innate immune system and host defense mechanism. METHODS: Here, we investigated a group of venoms (snakes, scorpions and honey bee venoms) for antimicrobial properties against two strains of Gram-negative bacteria Burkholderia pseudomallei by using disc-diffusion assay for in vitro susceptibility testing. The antibacterial activities of the venoms were compared with that of the isolated L-amino acid oxidase (LAAO) and phospholipase A(2 )(PLA(2)s) enzymes. MICs were determined using broth dilution method. Bacterial growth was assessed by measurement of optical density at the lowest dilutions (MIC 0.25 mg/ml). The cell viability was measured using tetrazolium salts (XTT) based cytotoxic assay. RESULTS: The studied venoms showed high antimicrobial activity. The venoms of C. adamanteus, Daboia russelli russelli, A. halys, P. australis, B. candidus and P. guttata were equally as effective as Chloramphenicol and Ceftazidime (30 μg/disc). Among those tested, phospholipase A(2 )enzymes (crotoxin B and daboiatoxin) showed the most potent antibacterial activity against Gram-negative (TES) bacteria. Naturally occurring venom peptides and phospholipase A(2 )proved to possess highly potent antimicrobial activity against Burkholderia pseudomallei. The XTT-assay results showed that the cell survival decreased with increasing concentrations (0.05–10 mg/mL) of Crotalus adamanteus venom, with no effect on the cell viability evident at 0.5 mg/mL. CONCLUSION: This antibacterial profile of snake venoms reported herein will be useful in the search for potential antibacterial agents against drug resistant microorganisms like B. pseudomallei

A Simple Scoring System to Differentiate between Relapse and Re-Infection in Patients with Recurrent Melioidosis

Melioidosis is a serious infectious disease caused by the Gram-negative bacterium, Burkholderia pseudomallei. This organism is present in the environment in areas where melioidosis is endemic (most notably East Asia and Northern Australia), and infection is acquired following bacterial inoculation or inhalation. Despite prolonged oral eradicative treatment, recurrent melioidosis occurs in approximately 10% of survivors of acute melioidosis. Recurrent melioidosis can be caused by relapse (failure of initial eradicative treatment) or re-infection with a new infection. The aim of this study was to develop a simple scoring system to distinguish between re-infection and relapse, since this has implications for antimicrobial treatment of the recurrent episode, but telling the two apart normally requires bacterial genotyping. A prospective study of melioidosis patients in NE Thailand conducted between 1986 and 2005 identified 141 patients with recurrent melioidosis. Of these, 92 patients had relapse and 49 patients had re-infection as confirmed by genotyping techniques. We found that relapse was associated with previous inadequate treatment and shorter time to clinical features of recurrence, while re-infection was associated with renal insufficiency and presentation during the rainy season. A simple scoring index to help distinguish between relapse and re-infection was developed to provide important bedside information where rapid bacterial genotyping is unavailable. Guidelines are provided on how this scoring system could be implemented

The Epidemiology and Clinical Spectrum of Melioidosis: 540 Cases from the 20 Year Darwin Prospective Study

Melioidosis is an occupationally and recreationally acquired infection important in Southeast Asia and northern Australia. Recently cases have been reported from more diverse locations globally. The responsible bacterium, Burkholderia pseudomallei, is considered a potential biothreat agent. Risk factors predisposing to melioidosis are well recognised, most notably diabetes. The Darwin prospective melioidosis study has identified 540 cases of melioidosis over 20 years and analysis of the epidemiology and clinical findings provides important new insights into this disease. Risk factors identified in addition to diabetes, hazardous alcohol use and chronic renal disease include chronic lung disease, malignancies, rheumatic heart disease, cardiac failure and age ≥50 years. Half of patients presented with pneumonia and septic shock was common (21%). The decrease in mortality from 30% in the first 5 years of the study to 9% in the last five years is attributed to earlier diagnosis and improvements in intensive care management. Of the 77 fatal cases (14%), all had known risk factors for melioidosis. This supports the most important conclusion of the study, which is that melioidosis is very unlikely to kill a healthy person, provided the infection is diagnosed early and resources are available to provide appropriate antibiotics and critical care where required