Time series analysis of demographic and temporal trends of tuberculosis in Singapore

Background: Singapore is an intermediate tuberculosis (TB) incidence country, with a recent rise in TB incidence from 2008, after a fall in incidence since 1998. This study identified population characteristics that were associated with the recent increase in TB cases, and built a predictive model of TB risk in Singapore. Methods: Retrospective time series analysis was used to study TB notification data collected from 1995 to 2011 from the Singapore Tuberculosis Elimination Program (STEP) registry. A predictive model was developed based on the data collected from 1995 to 2010 and validated using the data collected in 2011. Results: There was a significant difference in demographic characteristics between resident and non-resident TB cases. TB risk was higher in non-residents than in residents throughout the period. We found no significant association between demographic and macro-economic factors and annual incidence of TB with or without adjusting for the population-at-risk. Despite growing non-resident population, there was a significant decrease in the non-resident TB risk (p < 0.0001). However, there was no evidence of trend in the resident TB risk over this time period, though differences between different demographic groups were apparent with ethnic minorities experiencing higher incidence rates. Conclusion: The study found that despite an increasing size of non-resident population, TB risk among non-residents was decreasing at a rate of about 3% per year. There was an apparent seasonality in the TB reporting

A Study of Burkholderia pseudomallei in the Environment of Farms in Thanlyin and Hmawbi Townships, Myanmar.

Melioidosis is a tropical infection, first described in Myanmar but now rarely diagnosed there, which is widespread in Southeast Asia. The infection is predominantly acquired by people and animals through contact with soil or water. This study aimed to detect the causative organism, Burkholderia pseudomallei, in environmental samples from farms in Thanlyin and Hmawbi townships near Yangon, Myanmar. One hundred and twenty soil samples and 12 water samples were collected and processed using standard microbiological methods. Burkholderia species were isolated from 50 of the 120 (42%) soil samples but none of the water samples. Arabinose assimilation was tested to differentiate between B. pseudomallei and the nonpathogenic Burkholderia thailandensis, and seven of 50 isolates (14%) were negative. These were all confirmed as B. pseudomallei by a species-specific multiplex polymerase chain reaction (PCR). This is the first study to detect environmental B. pseudomallei in Myanmar and confirms that melioidosis is still endemic in the Yangon area

Myanmar Burkholderia pseudomallei strains are genetically diverse and originate from Asia with phylogenetic evidence of reintroductions from neighbouring countries.

Melioidosis was first identified in Myanmar in 1911 but for the last century it has remained largely unreported there. Burkholderia pseudomallei was first isolated from the environment of Myanmar in 2016, confirming continuing endemicity. Recent genomic studies showed that B. pseudomallei originated in Australia and spread to Asia, with phylogenetic evidence of repeated reintroduction of B. pseudomallei across countries bordered by the Mekong River and the Malay Peninsula. We present the first whole-genome sequences of B. pseudomallei isolates from Myanmar: nine clinical and seven environmental isolates. We used large-scale comparative genomics to assess the genetic diversity, phylogeography and potential origins of B. pseudomallei in Myanmar. Global phylogenetics demonstrated that Myanmar isolates group in two distantly related clades that reside in a more ancestral Asian clade with high amounts of genetic diversity. The diversity of B. pseudomallei from Myanmar and divergence within our global phylogeny suggest that the original introduction of B. pseudomallei to Myanmar was not a recent event. Our study provides new insights into global patterns of B. pseudomallei dissemination, most notably the dynamic nature of movement of B. pseudomallei within densely populated Southeast Asia. The role of anthropogenic influences in both ancient and more recent dissemination of B. pseudomallei to Myanmar and elsewhere in Southeast Asia and globally requires further study

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

Genotypic Heterogeneity of Orientia tsutsugamushi in Scrub Typhus Patients and Thrombocytopenia Syndrome Co-infection, Myanmar

Serologic and molecular surveillance of serum collected from 152 suspected scrub typhus patients in Myanmar revealed Orientia tsutsugamushi of genotypic heterogeneity. In addition, potential co-infection with severe fever with thrombocytopenia syndrome virus was observed in 5 (3.3%) patients. Both scrub typhus and severe fever with thrombocytopenia syndrome are endemic in Myanmar.Y

Risk factor-based screening compared to universal screening for gestational diabetes mellitus in marginalized Burman and Karen populations on the Thailand-Myanmar border: an observational cohort

Background: Gestational diabetes mellitus (GDM) contributes significantly to maternal and neonatal morbidity, but data from marginalized populations remains scarce. This study aims to compare risk-factor-based screening to universal testing for GDM among migrants along the Thailand-Myanmar border. Methods: From the prospective cohort (September 2016, February 2019), 374 healthy pregnant women completed a 75g oral glucose tolerance test (OGTT) at 24-32 weeks gestation. Fasting, one hour and two hour cut-offs were based on Hyperglycaemia and Adverse Pregnancy Outcomes (HAPO trial) criteria and cases were treated. The sensitivity and specificity of risk-factor-based screening criteria was calculated using OGTT as the gold standard. Risk factors included at least one positive finding among 10 criteria, e.g., obesity (body mass index (BMI) >/=27.5kg/m (2)), 1 (st) degree relative with diabetes etc. Adverse maternal and neonatal outcomes were compared by GDM status, and risk factors for GDM were explored. Results: GDM prevalence was 13.4% (50/374) (95% CI: 10.3-17.2). Risk-factors alone correctly identified 74.0% (37/50) OGTT positive cases: sensitivity 74.0% (59.7-85.4) and specificity 27.8% (3.0-33.0). Burman women accounted for 29.1% of the cohort population, but 38.0% of GDM cases. Percentiles for birthweight (p=0.004), head circumference (p=0.005), and weight-length ratio (p=0.010) were higher in newborns of GDM mothers compared with non-GDM, yet 21.7% (75/346) of newborns in the cohort were small-for-gestational age. In Burman women, overweight/obese BMI was associated with a significantly increased adjusted odds ratio 5.03 (95% CI: 1.43-17.64) for GDM compared to normal weight, whereas underweight and overweight/obese in Karen women were both associated with similarly elevated adjusted odds, approximately 2.4-fold (non-significant) for GDM. GDM diagnosis by OGTT was highest prior to peak rainfall. Conclusions: Risk-factor-based screening was not sufficiently sensitive or specific to be useful to diagnose GDM in this setting among a cohort of low-risk pregnant women. A two-step universal screening program has thus been implemented

Geographical distribution of Burkholderia pseudomallei in soil in Myanmar.

BACKGROUND: Burkholderia pseudomallei is a Gram-negative bacterium found in soil and water in many tropical countries. It causes melioidosis, a potentially fatal infection first described in 1911 in Myanmar. Melioidosis is a common cause of sepsis and death in South and South-east Asia, but it is rarely diagnosed in Myanmar. We conducted a nationwide soil study to identify areas where B. pseudomallei is present. METHODOLOGY/PRINCIPAL FINDINGS: We collected soil samples from 387 locations in all 15 states and regions of Myanmar between September 2017 and June 2019. At each site, three samples were taken at each of three different depths (30, 60 and 90 cm) and were cultured for B. pseudomallei separately, along with a pooled sample from each site (i.e. 10 cultures per site). We used a negative binomial regression model to assess associations between isolation of B. pseudomallei and environmental factors (season, soil depth, soil type, land use and climate zones). B. pseudomallei was isolated in 7 of 15 states and regions. Of the 387 sites, 31 (8%) had one or more positive samples and of the 3,870 samples cultured, 103 (2.7%) tested positive for B. pseudomallei. B. pseudomallei was isolated more frequently during the monsoon season [RR-2.28 (95% CI: 0.70-7.38)] and less in the hot dry season [RR-0.70 (95% CI: 0.19-2.56)] compared to the cool dry season, and in the tropical monsoon climate zone [RR-2.26; 95% CI (0.21-6.21)] compared to the tropical dry winter climate zone. However, these associations were not statistically significant. B. pseudomallei was detected at all three depths and from various soil types (clay, silt and sand). Isolation was higher in agricultural land (2.2%), pasture land (8.5%) and disused land (5.8%) than in residential land (0.4%), but these differences were also not significant. CONCLUSION/SIGNIFICANCE: This study confirms a widespread distribution of B. pseudomallei in Myanmar. Clinical studies should follow to obtain a better picture of the burden of melioidosis in Myanmar

CD or not CD, that is the question - a digital interobserver agreement study in coeliac disease

OBJECTIVE: Coeliac disease (CD) diagnosis generally depends on histological examination of duodenal biopsies. We present the first study analysing the concordance in examination of duodenal biopsies using digitised whole-slide images (WSIs). We further investigate whether the inclusion of IgA tTG and haemoglobin (Hb) data improves the inter-observer agreement of diagnosis.DESIGN: We undertook a large study of the concordance in histological examination of duodenal biopsies using digitised WSIs in an entirely virtual reporting setting. Our study was organised in two phases: in phase one, 13 pathologists independently classified 100 duodenal biopsies (40 normal; 40 CD; 20 indeterminate enteropathy) in the absence of any clinical or laboratory data. In phase two, the same pathologists examined the (re-anonymised) WSIs with the inclusion of IgA tTG and Hb data.RESULTS: We found the mean probability of two observers agreeing in the absence of additional data to be 0.73 (±0.08) with a corresponding Cohen's kappa of 0.59 (±0.11). We further showed that the inclusion of additional data increased the concordance to 0.80 (±0.06) with a Cohen's kappa coefficient of 0.67 (±0.09).CONCLUSION: We showed that the addition of serological data significantly improves the quality of CD diagnosis. However, the limited inter-observer agreement in CD diagnosis using digitised WSIs, even after the inclusion of IgA tTG and Hb data, indicates the important of interpreting duodenal biopsy in the appropriate clinical context. It further highlights the unmet need for an objective means of reproducible duodenal biopsy diagnosis, such as the automated analysis of WSIs using AI.<br/