Enhanced melioidosis surveillance in patients attending four tertiary hospitals in Yangon, Myanmar.

Abstract To investigate the current epidemiology of melioidosis in Yangon, Myanmar, between June 2017 and May 2019 we conducted enhanced surveillance for melioidosis in four tertiary hospitals in Yangon, where the disease was first discovered in 1911. Oxidase-positive Gram-negative rods were obtained from the microbiology laboratories and further analysed at the Department of Medical Research. Analysis included culture on Ashdown agar, the three disc sensitivity test (gentamicin, colistin and co-amoxiclav), latex agglutination, API 20 NE, antibiotic susceptibility testing, and a subset underwent molecular confirmation with a Burkholderia pseudomallei specific assay. Twenty one of 364 isolates (5.7%) were confirmed as B. pseudomallei and were mostly susceptible to the antibiotics used in standard therapy for melioidosis. Ten patients were from Yangon Region, nine were from Ayeyarwaddy region, and one each was from Kayin and Rakhine States. A history of soil contact was given by seven patients, five had diabetes mellitus and one had renal insufficiency. The patients presented with septicaemia (12 cases), pneumonia (three cases), urinary tract infection (two cases) and wound infection (four cases). Eighteen patients survived to hospital discharge. This study highlights the likelihood that melioidosis may be far more common, but underdiagnosed, in more rural parts of Myanmar as in other countries in SE Asia.</jats:p

Pediatric melioidosis in Sarawak, Malaysia: Epidemiological, clinical and microbiological characteristics

Background Melioidosis is a serious, and potentially fatal community-acquired infection endemic to northern Australia and Southeast Asia, including Sarawak, Malaysia. The disease, caused by the usually intrinsically aminoglycoside-resistant Burkholderia pseudomallei, most commonly affects adults with predisposing risk factors. There are limited data on pediatric melioidosis in Sarawak. Methods A part prospective, part retrospective study of children aged <15 years with culture-confirmed melioidosis was conducted in the 3 major public hospitals in Central Sarawak between 2009 and 2014. We examined epidemiological, clinical and microbiological characteristics. Findings Forty-two patients were recruited during the 6-year study period. The overall annual incidence was estimated to be 4.1 per 100,000 children <15 years, with marked variation between districts. No children had pre-existing medical conditions. Twenty-three (55%) had disseminated disease, 10 (43%) of whom died. The commonest site of infection was the lungs, which occurred in 21 (50%) children. Other important sites of infection included lymph nodes, spleen, joints and lacrimal glands. Seven (17%) children had bacteremia with no overt focus of infection. Delays in diagnosis and in melioidosis-appropriate antibiotic treatment were observed in nearly 90% of children. Of the clinical isolates tested, 35/36 (97%) were susceptible to gentamicin. Of these, all 11 isolates that were genotyped were of a single multi-locus sequence type, ST881, and possessed the putative B. pseudomallei virulence determinants bimABp, fhaB3, and the YLF gene cluster. Conclusions Central Sarawak has a very high incidence of pediatric melioidosis, caused predominantly by gentamicin-susceptible B. pseudomallei strains. Children frequently presented with disseminated disease and had an alarmingly high death rate, despite the absence of any apparent predisposing risk factor

Broad spectrum SARS‐CoV ‐2‐specific immunity in hospitalized First Nations peoples recovering from COVID ‐19

Indigenous peoples globally are at increased risk of COVID‐19‐associated morbidity and mortality. However, data that describe immune responses to SARS‐CoV‐2 infection in Indigenous populations are lacking. We evaluated immune responses in Australian First Nations peoples hospitalized with COVID‐19. Our work comprehensively mapped out inflammatory, humoral and adaptive immune responses following SARS‐CoV‐2 infection. Patients were recruited early following the lifting of strict public health measures in the Northern Territory, Australia, between November 2021 and May 2022. Australian First Nations peoples recovering from COVID‐19 showed increased levels of MCP‐1 and IL‐8 cytokines, IgG‐antibodies against Delta‐RBD and memory SARS‐CoV‐2‐specific T cell responses prior to hospital discharge in comparison with hospital admission, with resolution of hyperactivated HLA‐DR+CD38+ T cells. SARS‐CoV‐2 infection elicited coordinated ASC, Tfh and CD8+ T cell responses in concert with CD4+ T cell responses. Delta and Omicron RBD‐IgG, as well as Ancestral N‐IgG antibodies, strongly correlated with Ancestral RBD‐IgG antibodies and Spike‐specific memory B cells. We provide evidence of broad and robust immune responses following SARS‐CoV‐2 infection in Indigenous peoples, resembling those of non‐Indigenous COVID‐19 hospitalized patients

Robust and prototypical immune responses toward COVID-19 vaccine in First Nations peoples are impacted by comorbidities

High-risk groups, including Indigenous people, are at risk of severe COVID-19. Here we found that Australian First Nations peoples elicit effective immune responses to COVID-19 BNT162b2 vaccination, including neutralizing antibodies, receptor-binding domain (RBD) antibodies, SARS-CoV-2 spike-specific B cells, and CD4+ and CD8+ T cells. In First Nations participants, RBD IgG antibody titers were correlated with body mass index and negatively correlated with age. Reduced RBD antibodies, spike-specific B cells and follicular helper T cells were found in vaccinated participants with chronic conditions (diabetes, renal disease) and were strongly associated with altered glycosylation of IgG and increased interleukin-18 levels in the plasma. These immune perturbations were also found in non-Indigenous people with comorbidities, indicating that they were related to comorbidities rather than ethnicity. However, our study is of a great importance to First Nations peoples who have disproportionate rates of chronic comorbidities and provides evidence of robust immune responses after COVID-19 vaccination in Indigenous people

Tracing the environmental footprint of the Burkholderia pseudomallei lipopolysaccharide genotypes in the tropical "Top End" of the Northern Territory, Australia.

The Tier 1 select agent Burkholderia pseudomallei is an environmental bacterium that causes melioidosis, a high mortality disease. Variably present genetic markers used to elucidate strain origin, relatedness and virulence in B. pseudomallei include the Burkholderia intracellular motility factor A (bimA) and filamentous hemagglutinin 3 (fhaB3) gene variants. Three lipopolysaccharide (LPS) O-antigen types in B. pseudomallei have been described, which vary in proportion between Australian and Asian isolates. However, it remains unknown if these LPS types can be used as genetic markers for geospatial analysis within a contiguous melioidosis-endemic region. Using a combination of whole-genome sequencing (WGS), statistical analysis and geographical mapping, we examined if the LPS types can be used as geographical markers in the Northern Territory, Australia. The clinical isolates revealed that LPS A prevalence was highest in the Darwin and surrounds (n = 660; 96% being LPS A and 4% LPS B) and LPS B in the Katherine and Katherine remote and East Arnhem regions (n = 79; 60% being LPS A and 40% LPS B). Bivariate logistics regression of 999 clinical B. pseudomallei isolates revealed that the odds of getting a clinical isolate with LPS B was highest in East Arnhem in comparison to Darwin and surrounds (OR 19.5, 95% CI 9.1-42.0; p<0.001). This geospatial correlation was subsequently confirmed by geographically mapping the LPS type from 340 environmental Top End strains. We also found that in the Top End, the minority bimA genotype bimABm has a similar remote region geographical footprint to that of LPS B. In addition, correlation of LPS type with multi-locus sequence typing (MLST) was strong, and where multiple LPS types were identified within a single sequence type, WGS confirmed homoplasy of the MLST loci. The clinical, sero-diagnostic and vaccine implications of geographically-based B. pseudomallei LPS types, and their relationships to regional and global dispersal of melioidosis, require global collaborations with further analysis of larger clinically and geospatially-linked datasets

Pediatric melioidosis in Sarawak, Malaysia: Epidemiological, clinical and microbiological characteristics.

Melioidosis is a serious, and potentially fatal community-acquired infection endemic to northern Australia and Southeast Asia, including Sarawak, Malaysia. The disease, caused by the usually intrinsically aminoglycoside-resistant Burkholderia pseudomallei, most commonly affects adults with predisposing risk factors. There are limited data on pediatric melioidosis in Sarawak.A part prospective, part retrospective study of children aged <15 years with culture-confirmed melioidosis was conducted in the 3 major public hospitals in Central Sarawak between 2009 and 2014. We examined epidemiological, clinical and microbiological characteristics.Forty-two patients were recruited during the 6-year study period. The overall annual incidence was estimated to be 4.1 per 100,000 children <15 years, with marked variation between districts. No children had pre-existing medical conditions. Twenty-three (55%) had disseminated disease, 10 (43%) of whom died. The commonest site of infection was the lungs, which occurred in 21 (50%) children. Other important sites of infection included lymph nodes, spleen, joints and lacrimal glands. Seven (17%) children had bacteremia with no overt focus of infection. Delays in diagnosis and in melioidosis-appropriate antibiotic treatment were observed in nearly 90% of children. Of the clinical isolates tested, 35/36 (97%) were susceptible to gentamicin. Of these, all 11 isolates that were genotyped were of a single multi-locus sequence type, ST881, and possessed the putative B. pseudomallei virulence determinants bimABp, fhaB3, and the YLF gene cluster.Central Sarawak has a very high incidence of pediatric melioidosis, caused predominantly by gentamicin-susceptible B. pseudomallei strains. Children frequently presented with disseminated disease and had an alarmingly high death rate, despite the absence of any apparent predisposing risk factor

Prediction of Early Symptom Remission in Two Independent Samples of First-Episode Psychosis Patients Using Machine Learning

BACKGROUND: Validated clinical prediction models of short-term remission in psychosis are lacking. Our aim was to develop a clinical prediction model aimed at predicting 4−6-week remission following a first episode of psychosis. METHOD: Baseline clinical data from the Athens First Episode Research Study was used to develop a Support Vector Machine prediction model of 4-week symptom remission in first-episode psychosis patients using repeated nested cross-validation. This model was further tested to predict 6-week remission in a sample of two independent, consecutive Danish first-episode cohorts. RESULTS: Of the 179 participants in Athens, 120 were male with an average age of 25.8 years and average duration of untreated psychosis of 32.8 weeks. 62.9% were antipsychotic-naïve. Fifty-seven percent attained remission after 4 weeks. In the Danish cohort, 31% attained remission. Eleven clinical scale items were selected in the Athens 4-week remission cohort. These included the Duration of Untreated Psychosis, Personal and Social Performance Scale, Global Assessment of Functioning and eight items from the Positive and Negative Syndrome Scale. This model significantly predicted 4-week remission status (area under the receiver operator characteristic curve (ROC-AUC) = 71.45, P < .0001). It also predicted 6-week remission status in the Danish cohort (ROC-AUC = 67.74, P < .0001), demonstrating reliability. CONCLUSIONS: Using items from common and validated clinical scales, our model significantly predicted early remission in patients with first-episode psychosis. Although replicated in an independent cohort, forward testing between machine learning models and clinicians’ assessment should be undertaken to evaluate the possible utility as a routine clinical tool

Prediction of Early Symptom Remission in Two Independent Samples of First-Episode Psychosis Patients Using Machine Learning

Background: Validated clinical prediction models of short-term remission in psychosis are lacking. Our aim was to develop a clinical prediction model aimed at predicting 4-6-week remission following a first episode of psychosis.Method: Baseline clinical data from the Athens First Episode Research Study was used to develop a Support Vector Machine prediction model of 4-week symptom remission in first-episode psychosis patients using repeated nested cross-validation. This model was further tested to predict 6-week remission in a sample of two independent, consecutive Danish first-episode cohorts.Results: Of the 179 participants in Athens, 120 were male with an average age of 25.8 years and average duration of untreated psychosis of 32.8 weeks. 62.9% were antipsychotic-naive. Fifty-seven percent attained remission after 4 weeks. In the Danish cohort, 31% attained remission. Eleven clinical scale items were selected in the Athens 4-week remission cohort. These included the Duration of Untreated Psychosis, Personal and Social Performance Scale, Global Assessment of Functioning and eight items from the Positive and Negative Syndrome Scale. This model significantly predicted 4-week remission status (area under the receiver operator characteristic curve (ROC-AUC) = 71.45, P &lt;.0001). It also predicted 6-week remission status in the Danish cohort (ROC-AUC = 67.74, P &lt;.0001), demonstrating reliability.Conclusions: Using items from common and validated clinical scales, our model significantly predicted early remission in patients with firstepisode psychosis. Although replicated in an independent cohort, forward testing between machine learning models and clinicians’ assessment should be undertaken to evaluate the possible utility as a routine clinical tool

Average annual incidence of pediatric melioidosis by district within the Central region of Sarawak.

<p>The map of Borneo shows the Malaysian states of Sarawak and Sabah, and the location of the 3 study sites. The map insert depicts the average annual incidences of pediatric melioidosis in each district in Central Sarawak. The incidence per 100,000 children <15 years/ year, in each district, is labelled.</p