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IntroductionScrub typhus is a neglected tropical disease with an estimated 1 million cases annually. The Asia-Pacific region is an endemic area for scrub typhus, especially in Thailand.MethodsBetween June 2018 and December 2019, 31 patients with acute undifferentiated febrile illness (AUFI) were recruited for clinical trials and tested positive by a scrub typhus IgM RDT.ResultsOf the 17 buffy coat patient samples tested by 47kDa real-time PCR and 56kDa type-specific antigen (TSA) nested PCR, 94% (16/17) were positive, and of the 11 patients that presented with eschar lesions, 100% (11/11) of the eschar samples were confirmed positive. Genetic analysis of the 560 bp partial 56-kDa TSA gene demonstrated that most Orientia tsutsugamushi (Ot) infections were with Karp, Gilliam, Taiwan, P23, and CM606-like strains.DiscussionThis is the second occasion that the CM606-like and P23-like strains were reported in northern Thailand (first reported in 2011 and 2013, respectively). This study demonstrates that 1) the eschar remains the most reliable biological sample for PCR diagnosis of scrub typhus and 2) Northwestern Thailand has significant diversity of Ot strains, which underlines the requirement for ongoing surveillance to increase our understanding of Ot diversity to ensure accurate diagnostics and treatment.

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/m2), 1st 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.

BackgroundAntepartum depression affects around 15% of pregnant women worldwide, and may negatively impact their infants' physical, cognitive and social development, and confer a greater risk of emotional dysregulation in their children. Risk factors for antepartum depression disproportionately affect women from resource-sparse settings. In particular, pregnant refugee and migrant women face many barriers to diagnosis and care of mental health conditions, yet this group is under-represented in the literature. This study explores what refugee and migrant women living along the Thai-Myanmar border perceive as being contributory and protective factors to their antepartum depression, through secondary qualitative analysis of responses to clinical interviews for depression.MethodsPrevious research investigating perinatal depression in pregnant refugee and migrant women on the Thai-Myanmar border involved assessing 568 women for depression, using the Structured Clinical Interview for the diagnosis of DSM-IV Disorders (SCID). This study analyses a subsample of 32 women, diagnosed with persistent depression during the antepartum period. Thematic analysis of responses to the SCID and social and demographic surveys was undertaken to investigate factors which contribute towards, or protect against, persistent antepartum depression.ResultsMajor themes which women described as contributing towards persistent antepartum depression were financial problems, interpersonal violence, substance misuse among partners, social problems and poor health. Factors women considered as protecting mental wellbeing included social support, accessible healthcare and distractions, highlighting the need for focus on these elements within refugee and migrant settings. Commonly expressed phrases in local Karen and Burmese languages were summarised.ConclusionsKnowledge of factors affecting mental wellbeing in the study population and how these are phrased, may equip stakeholders to better support women in the study area. This study highlighted the limitations of contextually generic diagnostic tools, and recommends the development of tools better suited to marginalised and non-English speaking groups.

Background Soil-transmitted helminth (STH) infections are widespread in tropical and subtropical regions. While many STH infections are asymptomatic, vulnerable populations such as pregnant women face repercussions such as aggravation of maternal anaemia. However, data on prevalence and the effect of STH infections in pregnancy are limited. The aim of this analysis was to describe the burden of STH infections within and between populations of pregnant women from a local refugee camp to a mobile migrant population, and to explore possible associations between STH infection and pregnancy outcomes. Methodology This is a retrospective review of records from pregnant refugee and migrant women who attended Shoklo Malaria Research Unit antenatal care (ANC) clinics along the Thailand-Myanmar border between July 2013 and December 2017. Inclusion was based on provision of a stool sample during routine antenatal screening. A semi-quantitative formalin concentration method was employed for examination of faecal samples. The associations between STH mono-infections and maternal anaemia and pregnancy outcomes (i.e., miscarriage, stillbirth, preterm birth, and small for gestational age) were estimated using regression analysis. Principal findings Overall, 12,742 pregnant women were included, of whom 2,702 (21.2%) had a confirmed infection with either Ascaris lumbricoides, hookworm, Trichuris trichiura, or a combination of these. The occurrence of STH infections in the refugee population (30.8%; 1,246/4,041) was higher than in the migrant population (16.7%; 1,456/8,701). A. lumbricoides was the predominant STH species in refugees and hookworm in migrants. A. lumbricoides and hookworm infection were associated with maternal anaemia at the first ANC consultation with adjusted odds ratios of 1.37 (95% confidence interval (CI) 1.08–1.72) and 1.65 (95% CI 1.19–2.24), respectively. Pregnant women with A. lumbricoides infection were less likely to miscarry when compared to women with negative stool samples (adjusted hazard ratio 0.63, 95% CI 0.48–0.84). STH infections were not significantly associated with stillbirth, preterm birth or being born too small for gestational age. One in five pregnant women in this cohort had STH infection. Association of STH infection with maternal anaemia, in particular in the event of late ANC enrolment, underlines the importance of early detection and treatment of STH infection. A potential protective effect of A. lumbricoides infection on miscarriage needs confirmation in prospective studies., Author summary Soil-transmitted helminths (STHs) are parasitic worms transmitted through the faecal-oral or transcutaneous route. STHs are ubiquitous in tropical and subtropical regions where access to clean water, improved sanitation, and hygiene are lacking. STH infections are often asymptomatic; however, heavy infections can cause adverse effects such as abdominal discomfort and anaemia. Anaemia in pregnancy can increase the risk of pregnancy problems such as miscarriage, preterm delivery, and poor fetal growth. This retrospective analysis of routinely collected data from more than 12,000 pregnant refugee and migrant women who attended antenatal care clinics along the Thai-Myanmar border shows that one in five pregnant women were infected with STHs. Moreover, pregnant women with a STH infection were more likely to present with anaemia, suggesting that early presentation to antenatal care as well as anthelmintic treatment with subsequent anaemia prophylaxis may reduce the risk of anaemia. Interestingly, our data also indicate that STH infections may have beneficial effects on pregnancy outcomes, as miscarriage was less likely to occur in pregnancies with maternal STH infections. This finding was significant for infection with the roundworm Ascaris lumbricoides. Verification of these findings in prospective studies is warranted.

Preterm birth (PTB) is the most common cause of neonatal morbidity and mortality worldwide. Approximately half of PTBs is linked with microbial etiologies, including pathologic changes to the vaginal microbiota, which vary according to ethnicity. Globally more than 50% of PTBs occur in Asia, but studies of the vaginal microbiome and its association with pregnancy outcomes in Asian women are lacking. This study aimed to longitudinally analyzed the vaginal microbiome and cytokine environment of 18 Karen and Burman pregnant women who delivered preterm and 36 matched controls delivering at full term. Using 16S ribosomal RNA gene sequencing we identified a predictive vaginal microbiota signature for PTB that was detectable as early as the first trimester of pregnancy, characterized by higher levels of Prevotella buccalis, and lower levels of Lactobacillus crispatus and Finegoldia, accompanied by decreased levels of cytokines including IFNγ, IL-4, and TNFα. Differences in the vaginal microbial diversity and local vaginal immune environment were associated with greater risk of preterm birth. Our findings highlight new opportunities to predict PTB in Asian women in low-resource settings who are at highest risk of adverse outcomes from unexpected PTB, as well as in Burman/Karen ethnic minority groups in high-resource regions.

In rural areas of South and Southeast Asia malaria is declining but febrile illnesses still account for substantial morbidity and mortality. Village health workers (VHWs) are often the first point of contact with the formal health system, and for patients with febrile illnesses they can provide early diagnosis and treatment of malaria. However, for the majority of febrile patients, VHWs lack the training, support and resources to provide further care. Consequently, treatable bacterial illnesses are missed, antibiotics are overused and poorly targeted, and patient attendance wanes along with declining malaria. This Open Letter announces the start of a new initiative, the Rural Febrile Illness (RFI) project, the first in a series of projects to be implemented as part of the South and Southeast Asian Community-based Trials Network (SEACTN) research programme. This multi-country, multi-site project will begin in Bangladesh, Cambodia, Lao PDR, and Myanmar and will define the epidemiological baseline of febrile illness in five remote and underserved areas of Asia where malaria endemicity is declining and access to health services is limited. The RFI project aims to determine the incidence, causes and outcomes of febrile illness; understand the opportunities, barriers and appetite for adjustment of the role of VHWs to include management of non-malarial febrile illnesses; and establish a network of community healthcare providers and facilities capable of implementing interventions designed to triage, diagnose and treat patients presenting with febrile illnesses within these communities in the future.

Intestinal helminth infections are the most prevalent neglected tropical diseases, predominantly affecting rural and marginalised populations. The mainstay of diagnosis is the microscopic examination of faecal samples to detect parasites in the form of eggs, larvae and cysts. In an effort to improve the standard of care, the comparative accuracy in detecting helminth infections of the hitherto used formalin-based concentration method (FC) was compared to a previously developed formalin ethyl-acetate-based concentration technique (FECT), prior to the systematic deployment of the latter at a research and humanitarian unit operating on the Thailand–Myanmar border. A total of 693 faecal samples were available for the comparison of the two diagnostic methods. The FECT was superior in detecting hookworm, Trichuris trichiura and small liver flukes. Interestingly, there was no significant difference for Ascaris lumbricoides, possibly due to the high observed egg density. Despite the minor increase in material cost and the fact that the FECT is somewhat more time consuming, this method was implemented as the new routine technique.

In rural areas of South and Southeast Asia malaria is declining but febrile illnesses still account for substantial morbidity and mortality. Village health workers (VHWs) are often the first point of contact with the formal health system, and for patients with febrile illnesses they can provide early diagnosis and treatment of malaria. However, for the majority of febrile patients, VHWs lack the training, support and resources to provide further care. Consequently, treatable bacterial illnesses are missed, antibiotics are overused and poorly targeted, and patient attendance wanes along with declining malaria. This Open Letter announces the start of a new initiative, the Rural Febrile Illness (RFI) project, the first in a series of projects to be implemented as part of the South and Southeast Asian Community-based Trials Network (SEACTN) research programme. This multi-country, multi-site project will begin in Bangladesh, Cambodia, Lao PDR, and Myanmar and will define the epidemiological baseline of febrile illness in five remote and underserved areas of Asia where malaria endemicity is declining and access to health services is limited. The RFI project aims to determine the incidence, causes and outcomes of febrile illness; understand the opportunities, barriers and appetite for adjustment of the role of VHWs to include management of non-malarial febrile illnesses; and establish a network of community healthcare providers and facilities capable of implementing interventions designed to triage, diagnose and treat patients presenting with febrile illnesses within these communities in the future.

Non-intubated patients with acute respiratory failure due to COVID-19 could benefit from awake proning. Awake proning is an attractive intervention in settings with limited resources, as it comes with no additional costs. However, awake proning remains poorly used probably because of unfamiliarity and uncertainties regarding potential benefits and practical application. To summarize evidence for benefit and to develop a set of pragmatic recommendations for awake proning in patients with COVID-19 pneumonia, focusing on settings where resources are limited, international healthcare professionals from high and low- and middle-income countries (LMICs) with known expertise in awake proning were invited to contribute expert advice. A growing number of observational studies describe the effects of awake proning in patients with COVID-19 pneumonia in whom hypoxemia is refractory to simple measures of supplementary oxygen. Awake proning improves oxygenation in most patients, usually within minutes, and reduces dyspnea and work of breathing. The effects are maintained for up to 1 hour after turning back to supine, and mostly disappear after 6–12 hours. In available studies, awake proning was not associated with a reduction in the rate of intubation for invasive ventilation. Awake proning comes with little complications if properly implemented and monitored. Pragmatic recommendations including indications and contraindications were formulated and adjusted for resource-limited settings. Awake proning, an adjunctive treatment for hypoxemia refractory to supplemental oxygen, seems safe in non-intubated patients with COVID-19 acute respiratory failure. We provide pragmatic recommendations including indications and contraindications for the use of awake proning in LMICs.

Highlights • Globally, 10 % of birth are preterm and these are the leading cause of under 5-year mortality and disproportionally affect low-resource settings. • Gene expression profiling in maternal blood samples obtained during pregnancy has a high potential to identify pregnant women at risk of preterm birth. • To detect distinct transcriptome signatures, standardized protocols in cohorts commenced early in gestation and followed prospectively are key. • Gene expression profiling in maternal blood may guide targeted interventions to alleviate the risk of preterm birth., Objective To pursue a systematic review and summarise the current evidence for the potential of transcriptome molecular profiling in investigating the preterm phenotype. Study design We systematically reviewed the literature, using readily available electronic databases (i.e. PubMed/Medline, Embase, Scopus and Web of Science) from inception until March 2020 to identify investigations of maternal blood-derived RNA profiling in preterm birth (PTB). Studies were included if circulating coding or non-coding RNA was analysed in maternal blood during pregnancy and/or at delivery. Interventional trials were not included. The primary outcome was the availability of whole genome expression patterns evaluated in pregnancies resulting in preterm deliveries. Results A total of 35 articles were included in the final analysis. Most of the studies were conducted in high-income countries and published in the last decade. Apart from spontaneous PTB, a variety of phenotypes leading to preterm delivery were reported. Differences in sampling methods, target gene selection and laboratory protocols severely limited any quantitative comparisons. Most of the studies revealed that gene expression profiling during pregnancy has high potential for identifying women at risk of spontaneous and/or non-spontaneous PTB as early as in the first trimester. Conclusion Assessing maternal blood-derived transcriptional signatures for PTB risk in pregnant women holds promise as a screening approach. However, longitudinally followed, prospective pregnancy cohorts are lacking. These are relevant for identifying causes leading to PTB and whether prediction of spontaneous PTB or co-morbidities associated with PTB is achievable. More emphasis on widely employed standardised protocols is required to ensure comparability of results.

Background The Sustainable Development Goals (SDG) call for increased gender equity and reduction in malaria-related mortality and morbidity. Plasmodium vivax infections in pregnancy are associated with maternal anaemia and increased adverse perinatal outcomes. Providing radical cure for women with 8-aminoquinolines (e.g., primaquine) is hindered by gender-specific complexities. Case presentation A symptomatic episode of vivax malaria at 18 weeks of gestation in a primigravid woman was associated with maternal anaemia, a recurrent asymptomatic P. vivax episode, severe intra-uterine growth restriction with no other identifiable cause and induction to reduce the risk of stillbirth. At 5 months postpartum a qualitative glucose-6-phosphate dehydrogenase (G6PD) point-of-care test was normal and radical cure with primaquine was prescribed to the mother. A 33% fractional decrease in haematocrit on day 7 of primaquine led to further testing which showed intermediate phenotypic G6PD activity; the G6PD genotype could not be identified. Her infant daughter was well throughout maternal treatment and found to be heterozygous for Mahidol variant. Conclusion Adverse effects of vivax malaria in pregnancy, ineligibility of radical cure for pregnant and postpartum women, and difficulties in diagnosing intermediate levels of G6PD activity multiplied morbidity in this woman. Steps towards meeting the SDG include prevention of malaria in pregnancy, reducing unnecessary exclusion of women from radical cure, and accessible quantitative G6PD screening in P. vivax-endemic settings.

PurposeA successful pregnancy relies on the interplay of various biological systems. Deviations from the norm within a system or intersystemic interactions may result in pregnancy-associated complications and adverse pregnancy outcomes. Systems biology approaches provide an avenue of unbiased, in-depth phenotyping in health and disease. The molecular signature in pregnancy (MSP) cohort was established to characterise longitudinal, cross-omic trajectories in pregnant women from a resource constrained setting. Downstream analysis will focus on characterising physiological perturbations in uneventful pregnancies, pregnancy-associated complications and adverse outcomes.ParticipantsFirst trimester pregnant women of Karen or Burman ethnicity were followed prospectively throughout pregnancy, at delivery and until 3 months post partum. Serial high-frequency sampling to assess whole blood transcriptomics and microbiome composition of the gut, vagina and oral cavity, in conjunction with assessment of gene expression and microbial colonisation of gestational tissue, was done for all cohort participants.Findings to date381 women with live born singletons averaged 16 (IQR 15–18) antenatal visits (13 094 biological samples were collected). At 5% (19/381) the preterm birth rate was low. Other adverse events such as maternal febrile illness 7.1% (27/381), gestational diabetes 13.1% (50/381), maternal anaemia 16.3% (62/381), maternal underweight 19.2% (73/381) and a neonate born small for gestational age 20.2% (77/381) were more often observed than preterm birth.Future plansResults from the MSP cohort will enable in-depth characterisation of cross-omic molecular trajectories in pregnancies from a population in a resource-constrained setting. Moreover, pregnancy-associated complications and unfavourable pregnancy outcomes will be investigated at the same granular level, with a particular focus on population relevant needs such as effect of tropical infections on pregnancy. More detailed knowledge on multiomic perturbations will ideally result in the development of diagnostic tools and ultimately lead to targeted interventions that may disproportionally benefit pregnant women from this resource-limited population.Trial registration numberNCT02797327.

Brachybacterium is a genus of Gram-positive bacteria that rarely causes infections in humans. Here we report the case of an 8-month-old infant who presented with an acute febrile illness. During the diagnostic process, a blood culture was positive with Gram-positive cocci that were identified as Brachybacterium nesterenkovii by MALDI-TOF. As a result of the unclear clinical significance of this isolate and the continuous febrile state, a second blood culture was taken and returned B. nesterenkovii once more. To our knowledge this is the first time that B. nesterenkovii has been isolated from human blood cultures during the course of a systemic infection.

Background Covid-19 morbidity and mortality are associated with a dysregulated immune response. Tools are needed to enhance existing immune profiling capabilities in affected patients. Here we aimed to develop an approach to support the design of targeted blood transcriptome panels for profiling the immune response to SARS-CoV-2 infection. Methods We designed a pool of candidates based on a pre-existing and well-characterized repertoire of blood transcriptional modules. Available Covid-19 blood transcriptome data was also used to guide this process. Further selection steps relied on expert curation. Additionally, we developed several custom web applications to support the evaluation of candidates. Results As a proof of principle, we designed three targeted blood transcript panels, each with a different translational connotation: immunological relevance, therapeutic development relevance and SARS biology relevance. Conclusion Altogether the work presented here may contribute to the future expansion of immune profiling capabilities via targeted profiling of blood transcript abundance in Covid-19 patients.

In rural areas of South and Southeast Asia malaria is declining but febrile illnesses still account for substantial morbidity and mortality. Village health workers (VHWs) are often the first point of contact with the formal health system, and for patients with febrile illnesses they can provide early diagnosis and treatment of malaria. However, for the majority of febrile patients, VHWs lack the training, support and resources to provide further care. Consequently, treatable bacterial illnesses are missed, antibiotics are overused and poorly targeted, and patient attendance wanes along with declining malaria. This Open Letter announces the start of a new initiative, the Rural Febrile Illness (RFI) project, the first in a series of projects to be implemented as part of the South and Southeast Asian Community-based Trials Network (SEACTN) research programme. This multi-country, multi-site project will run in Bangladesh, Cambodia, Lao PDR, Thailand, and Myanmar. It will define the epidemiological baseline of febrile illness in nine remote and underserved areas of Asia where malaria endemicity is declining and access to health services is limited. The RFI project aims to determine the incidence, causes and outcomes of febrile illness; understand the opportunities, barriers and appetite for adjustment of the role of VHWs to include management of non-malarial febrile illnesses; and establish a network of community healthcare providers and facilities capable of implementing interventions designed to triage, diagnose and treat patients presenting with febrile illnesses within these communities in the future.

Resumo Objetivos Os pacientes com artrite reumatoide (AR) devem receber uma avaliacao do risco cardiovascular (CV). Para esse fim, existem as calculadoras de risco CV. Alem disso, parâmetros da funcao vascular podem ser medidos e usados para predicao do risco. O objetivo deste estudo foi avaliar a associacao entre esses dois conceitos. Metodos Foram incluidos neste estudo transversal 287 pacientes com AR (58,4 ± 12,6 anos) e 232 controles (49,9 ± 13,4 anos). Calculou‐se o risco CV em 10 anos com o Score e o QRISK2. No Score, usou‐se o multiplicador recomendado de 1,5 em pacientes com AR elegiveis e estimou‐se tambem o risco em pacientes com menos de 40 anos [mScore (0‐65)]. O indice de aumento (AIx) e a pressao de pulso (PP) central, marcadores da integridade vascular e risco CV, foram avaliados pela analise de onda de pulso (PWA). O desfecho primario foi a correlacao entre o AIx e o risco CV estimado com o mScore (0‐65). Resultados Em pacientes com AR, o AIx mostrou correlacao estatisticamente significativa com o mScore (0‐65) (rho = 0,3374; p Conclusoes Os parâmetros de hemodinâmica central se correlacionam com o risco CV calculado. No entanto, ambos nao fornecem exatamente as mesmas informacoes. Pergunta‐se se uma combinacao de ambos os conceitos resultaria em uma melhor predicao do risco CV.

Background: Eosinophilic meningitis (EOM) is a rare condition that is caused by various communicable and noncommunicable factors. The rat-lungworm Angiostrongylus cantonensis, which is associated with consumption of raw or undercooked paratenic or intermediate hosts, is the most common cause of parasitic eosinophilic meningitis worldwide. While the majority of A. cantonensis cases are reported from endemic regions, cases in travelers pose a challenge to clinicians in non-endemic countries. Here we report a rare case of eosinophilic meningitis caused by A. cantonensis in a Swiss traveler who was diagnosed after returning from Thailand.Case presentation: A 33-year old woman with a travel history to rural north-eastern Thailand presented to an emergency department in Switzerland with severe headache and vomiting. Eosinophilic meningitis was confirmed as the cause of the symptoms; however, serologic investigations failed to confirm an A. cantonensis infection on the first evaluation. Nevertheless, empirical treatment with an anthelminthic and steroid regimen led to a rapid alleviation of symptoms. Repeated serology confirmed seroconversion 2 weeks after treatment initiation.Discussion: Parasitic etiology must be considered in returning travelers who present with symptoms compatible with a central nervous system infection. A thorough medical history, including types of food consumed, is paramount and can often suggest differential diagnosis. Neuroangiostrongyliasis is rare and might be missed if serology does not cover possible seroconversion.

Objectives: Rheumatoid arthritis (RA) patients should receive cardiovascular (CV) risk assessment. For this purpose CV risk calculators are available. In addition, parameters of vascular function can be measured and used for risk prediction. Aim of the present study was to assess the association of these two concepts. Methods: 287 RA patients (58.4 ± 12.6 years) and 232 controls (49.9 ± 13.4 years) were included in this cross-sectional study. We calculated 10 year CV risk with SCORE and QRISK2. For SCORE we used the recommended multiplier of 1.5 in eligible RA patients and estimated the risk also in patients younger than 40 years (mSCORE (0-65)). Augmentation index (AIx) and central pulse pressure (PP), markers of vascular integrity and CV risk, were assessed by pulse wave analysis (PWA). Primary endpoint was the correlation of AIx and the estimated CV risk using mSCORE (0-65). Results: In RA patients AIx showed a statistically significant correlation with mSCORE (0-65) (rho = 0.3374; p < 0.0001) and QRISK2 (rho = 0.3307; p < 0.0001). The correlations of central PP with mSCORE (0-65) (rho = 0.4692; p < 0.0001) and QRISK2 (rho = 0.5828; p < 0.0001) were also statistically significant. Increasing quartiles of central PP were associated with an increased odds of being in the "high risk"category according to SCORE (OR 2.18; 95% CI 1.58-3.01) or QRISK2 (OR 2.18; 95% CI 1.75-2.72). In control patients we also found a correlation of AIx and central PP with SCORE (0-65) and QRISK2. Conclusions: Parameters of central haemodynamics correlate with calculated CV risk. However, both do not give exactly the same information. The question arises whether a combination of both concepts would result in an improved CV risk prediction. Resumo Objetivos: Os pacientes com artrite reumatoide (AR) devem receber uma avaliação do risco cardiovascular (CV). Para esse fim, existem as calculadoras de risco CV. Além disso, parâmetros da função vascular podem ser medidos e usados para predição do risco. O objetivo deste estudo foi avaliar a associação entre esses dois conceitos. Métodos: Foram incluídos neste estudo transversal 287 pacientes com AR (58,4 ± 12,6 anos) e 232 controles (49,9 ± 13,4 anos). Calculou-se o risco CV em 10 anos com o Score e o QRISK2. No Score, usou-se o multiplicador recomendado de 1,5 em pacientes com AR elegíveis e estimou-se também o risco em pacientes com menos de 40 anos [mScore (0-65)]. O índice de aumento (AIx) e a pressão de pulso (PP) central, marcadores da integridade vascular e risco CV, foram avaliados pela análise de onda de pulso (PWA). O desfecho primário foi a correlação entre o AIx e o risco CV estimado com o mScore (0-65). Resultados: Em pacientes com AR, o AIx mostrou correlação estatisticamente significativa com o mScore (0-65) (rho = 0,3374; p < 0,0001). A correlação entre o AIx e o QRISK2 também foi significativa (rho = 0,3307, p < 0,0001). As correlações entre a PP central e o mScore (0-65) (rho = 0,4692; p < 0,0001) e QRISK2 (rho = 0,5828; p < 0,0001) também foram estatisticamente significativas. Os quartis incrementais da PP central estiveram associados a uma maior probabilidade de estar na categoria de "alto risco"de acordo com o Score (OR 2,18; IC 95% 1,58 a 3,01) ou QRISK2 (OR 2,18; IC 95% 1,75-2,72). Nos pacientes do grupo controle também se encontrou uma correlação entre o AIx e a PP central no Score (0-65) e no QRISK2. Conclusões: Os parâmetros de hemodinâmica central se correlacionam com o risco CV calculado. No entanto, ambos não fornecem exatamente as mesmas informações. Pergunta-se se uma combinação de ambos os conceitos resultaria em uma melhor predição do risco CV.

Introduction: Scrub typhus is endemic in rural Southeast Asia. The district of Umphang in northwestern Thailand is a prototype environment for this disease. We report the clinical manifestations and outcomes of patients diagnosed with scrub typhus in this area. Methodology: Patients diagnosed with scrub typhus between 2011 and 2014 were analyzed. Diagnosis was based on clinical symptoms in conjunction with a positive rapid test or a pathognomonic eschar lesion. Results: A total of 857 patients were included, of which 488 were adults and 369 were children. Most patients (728; 84.9%) were included via a positive serology on rapid test, 86 patients (10.0%) had eschar only, and 43 patients (5.0%) had both sero-confirmation and presence of eschar. The most common symptom was fever (93.8%), followed by headache (48.1%) and cough (33.1%). Eschars were reported in 129 patients, with a significantly higher percentage in children (p < 0.001), and a different anatomical distribution was found when adults and children were compared. Common complications were elevated transaminases, acute kidney injury, and pneumonia. Most patients recovered from the disease. Conclusions: Scrub typhus in Umphang district is common. Patients can present with a variety of clinical symptoms, regardless of the presence of fever. Standard treatment led to a favorable outcome in most patients.

IntroductionPreterm birth (PTB) results from heterogeneous influences and is a major contributor to neonatal mortality and morbidity that continues to have adverse effects on infants beyond the neonatal period. This protocol describes the procedures to determine molecular signatures predictive of PTB through high-frequency sampling during pregnancy, at delivery and the postpartum period.Methods and analysisFour hundred first trimester pregnant women from either Myanmar or Thailand of either Karen or Burman ethnicity, with a viable, singleton pregnancy will be enrolled in this non-interventional, prospective pregnancy birth cohort study and will be followed through to the postpartum period. Fortnightly finger prick capillary blood sampling will allow the monitoring of genome-wide transcript abundance in whole blood. Collection of stool samples and vaginal swabs each trimester, at delivery and postpartum will allow monitoring of intestinal and vaginal microbial composition. In a nested case–control analysis, perturbations of transcript abundance in capillary blood as well as longitudinal changes of the gut, vaginal and oral microbiome will be compared between mothers giving birth to preterm and matched cases giving birth to term neonates. Placenta tissue of preterm and term neonates will be used to determine bacterial colonisation as well as for the establishment of coding and non-coding RNA profiles. In addition, RNA profiles of circulating, non-coding RNA in cord blood serum will be compared with those of maternal peripheral blood serum at time of delivery.Ethics and disseminationThis research protocol that aims to detect perturbations in molecular trajectories preceding adverse pregnancy outcomes was approved by the ethics committee of the Faculty of Tropical Medicine, Mahidol University in Bangkok, Thailand (Ethics Reference: TMEC 15–062), the Oxford Tropical Research Ethics Committee (Ethics Reference: OxTREC: 33–15) and the local Tak Province Community Ethics Advisory Board. The results of this cooperative project will be disseminated in multiple publications staggered over time in international peer-reviewed scientific journals.Trial registration numberNCT02797327; Pre-results.

Cyclophosphamide (CYC), primarily introduced into clinical practice as an anti-cancer substance, is a potent immunosuppressive drug. Today, it is used in a number of organ- or life -threatening autoimmune diseases such as systemic vasculitides or connective tissue diseases. While being effective, CYC has a small therapeutic index and is associated with significant toxicity. CYC has been used in oncology in a variety of diseases and a lot of data has been derived from this area. This knowledge is often extrapolated to the rheumatologic settings. However, besides some similarities substantial differences between these two specialties considering the underlying diseases as well as the kind of application of the drug exist. The aim of the present review is to describe the general characteristics of the use of CYC from the rheumatologist's point of view, including pharmacologic and pharmacokinetic properties, drug interactions, toxicity and possible preventive and/or therapeutic measures; all of which are important to consider when using this particular drug in the treatment of inflammatory rheumatic diseases.

Rheumatoid arthritis (RA) is associated with increased cardiovascular morbidity. It was previously shown that the augmentation index (AIx), a marker of vascular dysfunction, is higher in RA patients without traditional cardiovascular risk factors than in healthy controls. In this study we determined whether the impact of RA on the AIx is diminished in the context of coexisting, strong cardiovascular risk factors.A total of 411 participants were included [203 with RA; 208 in the non-RA (n-RA) group]. Pulse-wave analysis was performed on the radial artery using applanation tonometry. The impact of RA on the AIx was determined in a single and in a multiple linear regression model.The mean unadjusted AIx was 30.5 ± 9.0% for RA patients and 24.0 ± 11.0% for the n-RA group (P0.001). In the regression model, the following variables are statistically significant at approximately the same level (P0.001); the order of impact of these variables is agediastolic blood pressuresexRAheightsmoking status. RA, height, and smoking had a nearly equal impact on the AIx.The AIx is increased in RA patients regardless of the coexistence of traditional cardiovascular risk factors, thereby reflecting vascular dysfunction in this population. The impact of RA on the vascular system is comparable to that of smoking.

Aim Rheumatoid arthritis (RA) is associated with increased cardiovascular morbidity and mortality. In the general population, an increased heart rate is associated with increased mortality. Only a few studies have investigated heart rate in RA patients and compared the results with patients that do not have RA (n-RA). Therefore, little is known as to whether an increased heart rate, at least in part, could explain the increased mortality found in RA patients. The aim of the present study was to investigate whether heart rate is increased in RA patients. Methods In this cross-sectional study, heart rate was determined in a total of 282 patients (131 RA, 151 n-RA). In addition, non-invasive pulse wave analysis of the radial artery was performed to determine cardiac ejection duration using the Sphygmocor apparatus. Furthermore, the subendocardial viability ratio (SEVR), a marker of cardiac workload, was investigated, whereby higher values indicate a more favorable supply/demand relationship for the myocardium. Patients using chronotropic drugs were not included in the study. Results Heart rate was virtually the same in RA patients (71.9 ± 11.2 beats/min [bpm]) as compared with controls (72.3 ± 11.7 bpm; P > 0.05). Also SEVR (RA 144 ± 25% vs. n-RA 147 ± 27%; P > 0.05) and ejection duration (RA 321 ± 24 ms vs. n-RA 318 ± 24 ms; P > 0.05) were comparable between the groups. Conclusion It could not be shown that heart rate in RA patients differs significantly from heart rate in controls. Therefore, heart rate does not appear to explain or contribute to the increased cardiovascular risk found in RA patients.

A 10-year old otherwise healthy boy presented to Shoklo Malaria Research Unit migrant clinic on the Thailand-Myanmar border with a five-day history of high fever and tender swellings on the head, right-sided cervical (Fig. 1) and lumbar regions. Neither an inoculation event nor a breach in the skin continuity as a point of entry were evident and the patient did not travel to other regions before developing fever. No pus culture was obtained: aspiration was unsuccessful and as the abscesses failed to point, they could not be drained. A blood culture yielded Gram-negative rods, which were identified as Burkholderia pseudomallei, the causative agent of melioidosis. Initial empirical treatment was changed to ceftazidime and further abscesses were ruled out by an abdominal CT scan. The isolate obtained from the automated BacT/Alert (BioMerieux) blood culture was sent to Mahidol Oxford Tropical Medicine Research Unit where typical colony morphologies on Ashdown's agar were grown. Positive results to oxidase and latex agglutination test in addition to resistance to gentamicin and colistin confirmed the diagnosis. Fig. 1 Marked swelling on the right side of the neck corresponding to a subcutaneous abscess due to Burkholderia pseudomallei. Prolonged fever and undrained abscesses necessitated extended parenteral treatment with ceftazidime. Following eighteen days of treatment the fever subsided and after six weeks a marked clinical improvement enabled initiation of the oral eradication phase with trimethoprim/sulfamethoxazole. Melioidosis predominately affects patients with underlying medical conditions and leads to variable symptoms with sepsis and abscess formation commonly observed. In 2015 no other cases of melioidosis were reported in this province. This case is unusual, as the patient did not have any risk factors that are associated with severe melioidosis such as diabetes, chronic liver or chronic kidney disease and his presentation seemed more typical for a staphylococcal illness. This is a reminder that even though reports of B. pseudomallei infections in this area are rare, melioidosis should be considered for patients with abscess formation and potential sepsis in this region of Thailand and Myanmar, despite an absence of typical risk factors. Written informed consent was obtained from the patients’ legal guardian for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.