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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.

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.

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.

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.

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.