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Purpose of Review This review draws together recent publications, consensus statements on sarcoidosis and our 25-year collective experience in managing this disease. We focus on pulmonary sarcoidosis, highlighting recent and established concepts in disease mechanisms, the diversity of the clinical course, including possible ‘subtypes’ of sarcoidosis, and how to measure disease activity. We discuss the principles guiding therapeutic intervention and summarise the more recent clinical trials in sarcoidosis. Recent Findings These include recent progress in understanding the mechanisms of disease using new scientific tools, measurements of disease activity using CT and MRI scans, and the potential role of anti-fibrotic treatment for patients with progressive fibrotic sarcoidosis. Summary Sarcoidosis is a heterogeneous disease with variable organ involvement, disease course, and response to treatment. We offer an angle on when and how to treat, and provide an overall roadmap for managing sarcoidosis.

All four serotypes of the dengue virus (DENV1–4) cause a phenotypically similar illness, but serial infections from different serotypes increase the risk of severe disease. Thus, genomic surveillance of circulating viruses is important to detect serotype switches that precede community outbreaks of disproportionate magnitude. A phylogenetic analysis was conducted on near full length DENV genomes sequenced from serum collected from a prospective cohort study from the Colombo district, Sri Lanka during a 28-month period using Oxford nanopore technology, and the consensus sequences were analyzed using maximum likelihood and Bayesian evolutionary analysis. From 523 patients, 328 DENV sequences were successfully generated (DENV1: 43, DENV2: 219, DENV3:66). Most circulating sequences originated from a common ancestor that was estimated to have existed from around 2010 for DENV2 and around 2015/2016 for DENV1 and DENV3. Four distinct outbreaks coinciding with monsoon rain seasons were identified during the observation period mostly driven by DENV2 cosmopolitan genotype, except for a large outbreak in 2019 contributed by DENV3 genotype I. This serotype switch did not result in a more clinically severe illness. Phylogeographic analyses showed that all outbreaks started within Colombo city and then spread to the rest of the district. In 2019, DENV3 genotype I, previously, rarely reported in Sri Lanka, is likely to have contributed to a disease outbreak. However, this did not result in more severe disease in those infected, probably due to pre-existing DENV3 immunity in the community. Targeted vector control within Colombo city before anticipated seasonal outbreaks may help to limit the geographic spread of outbreaks.

Severe lung damage resulting from COVID-19 involves complex interactions between diverse populations of immune and stromal cells. In this study, we used a spatial transcriptomics approach to delineate the cells, pathways, and genes present across the spectrum of histopathological damage in COVID-19-affected lung tissue. We applied correlation network-based approaches to deconvolve gene expression data from 46 areas of interest covering more than 62,000 cells within well-preserved lung samples from 3 patients. Despite substantial interpatient heterogeneity, we discovered evidence for a common immune-cell signaling circuit in areas of severe tissue that involves crosstalk between cytotoxic lymphocytes and pro-inflammatory macrophages. Expression of IFNG by cytotoxic lymphocytes was associated with induction of chemokines, including CXCL9, CXCL10, and CXCL11, which are known to promote the recruitment of CXCR3+ immune cells. The TNF superfamily members BAFF (TNFSF13B) and TRAIL (TNFSF10) were consistently upregulated in the areas with severe tissue damage. We used published spatial and single-cell SARS-CoV-2 data sets to validate our findings in the lung tissue from additional cohorts of patients with COVID-19. The resulting model of severe COVID-19 immune-mediated tissue pathology may inform future therapeutic strategies.

Background Dengue could cause complications with an estimated 10,000 deaths per annum. It mostly affects low- and middle-income countries such as Sri Lanka with limited healthcare resources to handle seasonal outbreaks. A third of dengue patients usually have a critical phase characterized by plasma leakage with increased risk of life-threatening complications. A data-driven approach was required to find early predictors of plasma leakage that are usually available in routine care from a resource limited setting, as means of triaging patients for hospital admission. Methods We utilized a prospective cohort (The Colombo dengue study in Sri Lanka) that recruits patients meeting the clinical case definition of dengue fever. The cohort includes 4,781 instances of clinical signs, symptoms, and in-hospital laboratory tests from N=877 patients (60.3% patients infected by Dengue) recorded in first four days of fever. By excluding incomplete patient instances, the data was randomly split to a development set (N=378) and a test set (N=144). From the development set, five most informative features were identified using the minimum description length (MDL) algorithm. Logistic regression was used to create a prediction model using the development set. Shapley analysis was used to explain the model on the test set extracting the extent by which each predictor contributed to the predictions. Results The MDL algorithm revealed that hemoglobin (HGB), hematocrit (HCT), aspartate aminotransferase (AST), age, and gender to be the most informative predictors of plasma leakage. The logistic regression model predicted plasma leakage with (AUC = 0.76) on the test set (Fig 1). The HGB appeared to contribute the most to the predictions with the higher values associated with higher predicted risk of plasma leakage and vice versa (Fig 2). Figure 2 SHAP decision plot for the logistic regression model on the test set. The features are sorted from top to bottom by their mean absolute SHAP values (higher interpreted as more contributing). Feature values are normalised to [0 1] by the min-max normalisation method and colour-coded (grey points are missing values), outliers were squished to the range using Hampel filter. For gender, male is indicated by red and female by blue. The colour of each line is the same as the value of the feature connected to in downwards direction. Conclusion Our results give support to the predictability of plasma leakage in patients suspected of Dengue fever in their first four days of fever onset. The study also underlines the relevance of the machine learning approach to identify the predictors and the practicality of the prediction model as reflected by the prediction performance to triage patients for hospital admission in resource limited settings. Disclosures All Authors: No reported disclosures.

Current methods for dengue virus (DENV) genome amplification, amplify parts of the genome in at least 5 overlapping segments and then combine the output to characterize a full genome. This process is laborious, costly and requires at least 10 primers per serotype, thus increasing the likelihood of PCR bias. We introduce an assay to amplify near full-length dengue virus genomes as intact molecules, sequence these amplicons with third generation “nanopore” technology without fragmenting and use the sequence data to differentiate within-host viral variants with a bioinformatics tool (Nano-Q). The new assay successfully generated near full-length amplicons from DENV serotypes 1, 2 and 3 samples which were sequenced with nanopore technology. Consensus DENV sequences generated by nanopore sequencing had over 99.5% pairwise sequence similarity to Illumina generated counterparts provided the coverage was > 100 with both platforms. Maximum likelihood phylogenetic trees generated from nanopore consensus sequences were able to reproduce the exact trees made from Illumina sequencing with a conservative 99% bootstrapping threshold (after 1000 replicates and 10% burn-in). Pairwise genetic distances of within host variants identified from the Nano-Q tool were less than that of between host variants, thus enabling the phylogenetic segregation of variants from the same host.

Background: Reduced hemoglobin concentration has an adverse impact on the ischemic penumbra in patients with ischemic stroke as it causes reduced oxygen delivery to neuronal tissue and predisposes to infarct expansion. There is a paucity of data on the impact of anemia on early functional outcomes. Aims: To determine the association of anemia on early functional outcomes in a cohort of patients with ischemic stroke. Methods: This prospective study was conducted among 190 participants with acute ischemic stroke presenting to the National Hospital of Sri Lanka. Data were collected on socio-demographic determinants, clinical presentation, co-morbidities, subtype of stroke, and stroke severity (NIHSS score). Early functional outcomes were assessed by the Modified-Rankin-Score (mRS) and Barthel index (BI) within 48 h of the onset. Anemia was defined as Hb 3 (adjusted OR = 2.36; 95% CI = 1.1–5.1). Receiver operator characteristics (ROC) curves indicated a Hb% of 10.65 g/dl as the cut-off that would predict stroke-related disability assessed by mRS >3 [sensitivity = 86.7%; specificity = 34.2%; and AUC = 0.659 (P < 0.0001)]. Conclusions: Anemia is an independent determinant of poor functional disability in early acute ischemic stroke.

Background: The critical phase of dengue carries a high risk of bleeding. Associations of coagulation test parameters and the risk of bleeding in the critical phase is unclear. This study examines the association of rotational thromboelastometry (ROTEM delta and ROTEM platelet) with bleeding risk of patients with dengue in the critical phase. Methods: A total of 105 patients with confirmed dengue in the critical phase were recruited, with two subsequent prospective time point analyses of ROTEM parameters and platelet count within 24 and 48 hours from the onset of the critical phase. Conventional coagulation tests were performed only at the initial time point. Results: Twenty of 105 patients developed bleeding after onset of the critical phase. Within the first 24 hours of critical-phase onset, platelet count, coagulation tests, and ROTEM delta were unable to differentiate patients with bleeding manifestations from those without (P

Background Carica papaya (CP) extract is becoming popular as an unlicensed herbal remedy purported to hasten recovery in dengue infection, mostly based on observations that it may increase platelet counts. This systematic review and meta-analysis aims to critically analyze the evidence from controlled clinical trials on the efficacy and safety of CP extract in the treatment of dengue infection. Methods PubMed, LILACS and Google Scholar were searched for randomized or non-randomized trials enrolling patients with suspected or confirmed dengue where CP extract was compared, as a treatment measure, against standard treatment. Recovery of platelet counts as well as other clinical indicators of favourable outcome (duration of hospital stay, prevention of plasma leakage, life threatening complications, and mortality) were assessed. Results Nine studies (India-6, Pakistan-1, Indonesia-1, Malaysia-1) met the inclusion criteria. Seven studies showed an increase in platelet counts in patients receiving CP extract, while one study showed no significant difference between the two groups, and direct comparison was not possible in the remaining study. Serious adverse events were not reported. CP extract may reduce the duration of hospital stay (mean difference − 1.98 days, 95% confidence interval − 1.83 to − 2.12, 3 studies, 580 participants, low quality evidence), and cause improvement in mean platelet counts between the first and fifth day of treatment (mean difference 35.45, 95% confidence interval 23.74 to 47.15, 3 studies, 129 participants, low quality evidence). No evidence was available regarding other clinical outcomes. Conclusions The clinical value of improvement in platelet count or early discharge is unclear in the absence of more robust indicators of favourable clinical outcome. Current evidence is insufficient to comment on the role of CP extract in dengue. There is a need for further well designed clinical trials examining the effect of CP on platelet counts, plasma leakage, other serious manifestations of dengue, and mortality, with clearly defined outcome measures.

Background A major challenge in dengue management in resource limited settings is the confirmation of diagnosis. Clinical features of dengue often overlap with other infections and molecular diagnostic tools are not readily accessible to clinicians at hospitals. In addition, the prediction of plasma leakage in dengue is also difficult. Hematocrit level and ultrasound scans (combined with clinical parameters) are helpful to detect plasma leakage once it has happened, not before. Methods Colombo Dengue Study (CDS) is a prospective cohort study of clinically suspected adult dengue patients recruited from the National hospital of Sri Lanka (within the first 3 days of fever) that aimed to a) identify clinical and basic laboratory test parameters to differentiate dengue from non-dengue fever, b) evaluate the comparative efficacy of loop-mediated isothermal amplification (LAMP) for dengue diagnosis (vs. NS1 antigen test and RT-qPCR) and c) identify early associations that are predictive of plasma leakage or severe dengue. The basic laboratory tests considered here included hematological parameters, serum biochemistry and inflammatory markers. Results Only 70% of clinically suspected patients were confirmed as having dengue by either the NS1 antigen test or RT-qPCR. On a Bayesian latent class model which assumes no “gold standard”, LAMP performed equally or better than RT-qPCR and NS1 antigen test respectively. When confirmed dengue patients were compared with others, the earlier group had significantly lower lymphocyte counts and higher aspartate aminotransferase levels (AST) within the first 3 days of fever. Confirmed dengue patients with plasma leakage had a lower mean age and a higher median baseline AST level compared to those without plasma leakage (p

Life threatening macrovascular and microvascular complications of diabetes can be minimized by effective glycaemic control. Self monitoring of blood glucose with glucometers is recognized as a cost effective strategy to improve glycaemic control. However accuracy and precision of glucometers will determine the effectiveness of this strategy. We aimed to evaluate accuracy and precision of commonly used glucometers in Sri Lanka.An observational study was conducted in a tertiary care setting including patients with diabetes and healthy volunteers. Eight commonly used glucometers were used. Blood glucose was measured in 50 participants (16 healthy volunteers, 34 patients with diabetes) in finger prick capillary blood using glucometers and venous blood using standard laboratory methods, and were compared to determine accuracy. Repeated measurements from same glucometer with a single finger prick were made and compared to determine precision.Only one glucometer showed insignificant difference to venous plasma glucose values. Only one glucometer met ADA recommended bias of5%. None of the glucometers fell within the ISO recommendations for accuracy.Majority of commonly used glucometers in Sri Lanka do not meet the ADA recommendations and ISO standards for accuracy and precision. However their variations are unlikely to make significant adverse impact on patient management.

Dengue infection classically presents with fever, thrombocytopaenia, and varying degrees of plasma leakage, giving rise to shock. However, a myriad of other manifestations, involving the cardiovascular system, the nervous system, the liver, the kidneys, the gut and the haematological system have been reported in dengue. This review summarizes these varied presentations.

Objectives To compare the traditional hematocrit-based criteria (>20% rise above baseline) with ultrasonography for diagnosing plasma leakage in dengue fever and to identify clinical indicators for triaging patients in resource-limited settings when the demand for ultrasonography is high. Methods The Colombo Dengue Study is a prospective observational cohort study recruiting dengue patients in the first three days of dengue fever, before plasma leakage. Serial hematocrit assessments and ultrasonography were performed in patients recruited from October 2017 to February 2020. Clinical signs/symptoms and laboratory investigation results independently associated with ultrasound detected plasma leakage were identified with a derivation cohort and confirmed in a validation cohort. Results 129 of 426 patients had ultrasonography-confirmed plasma leakage while 146 had a hematocrit rise >20%. Those positive on ultrasonography were also likely to fulfill the hematocrit-based criteria (OR: 4.42, 95% CI: 2.85 - 6.86), but the two groups did not overlap fully. In the derivation cohort (n-317), platelet count 51 IU/L and having abdominal pain in the first three days of fever were independent predictors of ultrasound-detected plasma leakage. In the validation cohort (n-109), the combination of low platelet count and high aminotransferase level had better predictive capacity in terms of sensitivity and specificity. Conclusion Dengue patients should be monitored with both serial hematocrit and ultrasonography whenever possible and plasma leakage should be diagnosed by either one of these criteria. If accessibility to scans is limited, platelet count, serum transaminase levels and presence of abdominal pain are useful to triage patients.

Objectives This is a protocol for a Cochrane Review (diagnostic). The objectives are as follows: To assess the diagnostic accuracy of near‐patient tests for G6PD deficiency in people undergoing treatment or prophylaxis with primaquine or tafenoquine for malaria; or in people at risk of or susceptible to malaria. Secondary objectives To investigate sources of heterogeneity, namely the following. Age: adults versus children Sex: male versus female Reported prevalence of G6PD (high versus low) Malaria endemicity (endemic versus non‐endemic) Geographic location (continent of residence; that is, Africa, Asia, or other continent) Reference standard used (adjusted male median, median G6PD, laboratory standard) Type of blood used (venous versus capillary) To compare the accuracy of each type of test.

Background Previous studies on post-infection fatigue in dengue are few but suggest that up to 25% of dengue patients may suffer from fatigue. This study aimed to evaluate the prevalence and associations of post-infection fatigue in dengue patients compared with non-dengue fever patients. Methods Post-infection fatigue and its demographic and clinical associations were assessed in adult dengue and non-dengue fever patients 2 months after the acute infection in a prospective cohort study in Sri Lanka. Fatigue at 2 months (primary endpoint) was assessed with the fatigue questionnaire as a dichotomous outcome based on a pre-recommended cut-off (score ≥4) and as the total score from the questionnaire (higher score indicates more fatigue). Results Of 260 patients, 158 had dengue and, of these, 51 (32%) had fatigue at 2 months. Risk was higher in dengue patients (vs non-dengue; relative risk [RR] 4.93 [95% confidence interval {CI} 2.3 to 10.4]) and more so in female dengue patients (vs male dengue patients; RR 2.45 [95% CI 1.24 to 4.86]). Severe dengue patients had a higher mean fatigue score (p=0.024). Conclusions Post-infection fatigue is an underappreciated burden of this widely prevalent infection. Our findings are useful to triage patients at risk of fatigue for follow-up.

Leptospirosis is endemic in Sri Lanka. There is a need for updated seroprevalence studies in endemic areas, to improve the understanding of disease dynamics, risk factors, control methods, and for clinical diagnosis. The cut-off titres for the microscopic agglutination test (MAT) for diagnosis of acute leptospirosis depend on community seroprevalence, and can vary based on locality and serovar. This study aimed to identify the seroprevalence, geographical determinants, and associations of seropositivity of leptospirosis in the district of Colombo in Sri Lanka, and to determine diagnostic cut-off titres for MAT in the community studied. This study utilized a stratified cluster sampling model in the Colombo district of Sri Lanka, to sample individuals living in urban and semi-urban areas. Serovar specific MAT titres were measured on recruited individuals using a panel of saprophytic (Leptospira biflexa) and 11 pathogenic Leptospira spp. serovars. Associations between environmental risk factors and MAT positivity were examined, with location mapping using GIS software. A total of 810 individuals were included. The mean age was 51.71 years (SD 14.02) with male predominance (60%). A total of 429 (53%) tested positive at a titer of 1/40 or more for the saprophytic Leptospira biflexa serovar Patoc. Pathogenic serovar MAT was positive at a titer of 1/40 or more for at least one serovar in 269 (33.2%) individuals. From the perspective of screening for clinical disease, serovar-specific cut-off titres of 1/80 for Leptospira spp. serovars Hebdomadis, Icterohaemorrhagiae, Pomona, Ratnapura and Patoc, 1/160 for serovars Pyrogenes and Cynopteri, and 1/40 for other serovars were determined, based on the 75th quartile MAT titre for each serovar. Serovar Pyrogenes (15.9%) had the highest seroprevalence, with serovars Ratnapura, Bankinang and Australis accounting for 9.9%, 9.6% and 9.3% respectively. When the proposed new cut-offs were applied, Bankinang(9.6%) Australis(9.3%), Pyrogenes(6.9%) and Ratnapura(6.9%) were the most prevalent serovars. No significant differences in seroprevalence or serovar patterns were noted between urban and semi-urban settings. Individuals seropositive for Australis, Ratnapura and Icterohaemorrhagiae were clustered around main water bodies as well as around smaller tributaries and paddy fields. Those positive for the serovar Pyrogenes were clustered around inland tributaries, smaller water sources and paddy fields. Associations of MAT positivity included high risk occupational exposure, environmental exposure including exposure to floods, bathing in rivers and lakes, using well-water for bathing, contact with stagnant water, propensity to skin injuries, presence of rats in the vicinity, and proximity to water sources. For pathogenic serovars, high-risk occupational exposure remained statistically significant following adjustment for other factors (adjusted OR = 2.408, CI 1.711 to 3.388; p, Author summary Leptospirosis is a bacterial infection found widely among animals, which can also infect humans. Human disease results in fever, with acute damage to the liver and kidney occurring in severe cases. Around 58,900 deaths are estimated to occur worldwide from leptospirosis. In Sri Lanka, where the disease is widely prevalent, leptospirosis is commonly seen as a disease of farmers. Humans are infected through contact with rat urine, especially during paddy cultivation. In recent times, increasing numbers of cases are being reported in urban and semi-urban areas, as overcrowding, flooding, and poor sanitation provide an environment conducive to the transmission of leptospirosis. There are many serological types of leptospirosis, and the prevalence of these different serological variations (serovars) differ according to locality and animal host. The disease manifestations vary depending on, among other factors, the infecting serovar. Leptospirosis is commonly diagnosed using the microscopic agglutination test (MAT), which tests for both IgM and IgG antibodies. There is little information available about the baseline presence of antibodies to leptospirosis in community settings. In this study, a representative sample from the community was studied to determine the seroprevalence of leptospirosis (presence of antibodies to leptospirosis), from the district of Colombo in Sri Lanka. The Colombo district represents an urban/semi-urban area of Sri Lanka, where overcrowding is common, and flooding takes place often. Leptospirosis has shown a sharp increase in the Colombo district in recent years. The aim of this study was to determine two important aspects; the patterns of seroprevalence of common serological types, relating them to geographical and other risk factors, and to determine baseline cut-off values for antibody levels in the community. The latter is of great importance when using MAT to diagnose patients presenting with acute disease. This study found a relationship between the presence of seroconversion to pathogenic Leptospira types and high risk occupational exposures, environmental exposures including exposure to floods, bathing in rivers and lakes, using well water for bathing, contact with stagnant water, propensity to skin injuries, presence of rats in the vicinity, and proximity to water sources. It was also found that seropositivity for pathogenic Leptospira was lower than that for non-pathogenic species, reinforcing the importance of performing serovar-specific MAT for diagnosis. The cut-off titres for different serovars were found to differ, and were lower than the titres of ≥1/400 or ≥1/320 which are currently recommended by the World Health Organization and by local reference laboratories, respectively. This finding has important implications when determining the MAT titre cut-off for confirming the diagnosis of acute leptospirosis in patients with a suggestive clinical presentation.

Objectives The objective was to assess the effect of propranolol on oxidative stress and anti-oxidant potential in patients with resistant hypertension as a secondary analysis of the APPROPRIATE trial. This randomized double blinded clinical trial recruited patients with resistant hypertension and allocated forty patients to propranolol and placebo in 1:1 ratio. The pro-oxidant state (nitrate and nitrite) was assessed using modified Griess assay. The total anti-oxidant capacity was measured using ABTS assay. Results Analysis was performed for 18 patients from the propranolol group and 15 from the placebo group. A decline in end point ambulatory blood pressure (p = 0.031) and greater mean reduction in office SBP (29.7 ± 13.0 mmHg, p = 0.021) was noted in the propranolol arm. Nitrate and nitrite levels were lower at the end of a 90 day follow up period in both arms, with a greater mean reduction with propranolol. A significant increase in the AOC was noted in both arms with higher incremental value with Propranolol. The findings of this study do not demonstrate a statistically significant effect of propranolol on the oxidative stress/antioxidant balance in patients with resistant hypertension. The observed trends merit further evaluation.

Background Aspergillosis is a serious infection particularly affecting the immunodeficient host. Its co-infection with tuberculosis and cytomegalovirus has not been reported before. Embolic events are well recognized with aspergillous endocarditis and aortitis. Splenic abscess is a rare serious complication of disseminated aspergillosis and is difficult to treat. We report the first case of multiple embolic events and splenic abscess in a patient with pulmonary aspergillosis and cytomegaloviral and tuberculous co-infection, without endocarditis or aortitis. Case presentation Thirty-year-old male presented with fever and non-productive cough while on glucocorticoids for glomerulonephritis. He was found to have pulmonary aspergillosis and subsequently developed bilateral lower limb and cerebral fungal emboli and fungal abscess in the spleen. He had IgM and B cell deficiency and cytomegalovirus (CMV) and tuberculous co-infections. He recovered after prolonged course of antimicrobials, splenectomy and cessation of glucocorticoid therapy which also lead to the resolution of immune deficiencies. Conclusion This report illustrates rare combination of B and T cell suppressive effects of glucocorticoids leading to co-infections with CMV, Mycobacterium tuberculosis and Aspergillus and systemic fungal embolization from pulmonary aspergillosis. Electronic supplementary material The online version of this article (10.1186/s12879-018-3293-4) contains supplementary material, which is available to authorized users.

Introduction The cost in managing hospitalised dengue patients varies across countries depending on access to healthcare, management guidelines, and state sponsored subsidies. For health budget planning, locally relevant, accurate costing data from prospective studies, is essential. Objective To characterise the direct costs of managing hospitalised patients with suspected dengue infection in Sri Lanka. Methods Colombo Dengue Study is a prospective single centre cohort study in Sri Lanka recruiting suspected hospitalised dengue fever patients in the first three days of fever and following them up until discharge. The diagnosis of dengue is retrospectively confirmed and the cohort therefore has a group of non-dengue fever patients with a phenotypically similar illness, managed as dengue while in hospital. The direct costs of hospital admission (base and investigation costs, excluding medication) were calculated for all recruited patients and compared between dengue and non-dengue categories as well as across subgroups (demographic, clinical or temporal) within each of these categories. We also explored if excluding dengue upfront, would lead to an overall cost saving in several hypothetical scenarios. Results From October 2017 to February 2020, 431 adult dengue patients and 256 non-dengue fever patients were recruited. The hospitalisation costs were USD 18.02 (SD: 4.42) and USD 17.55 (SD: 4.09) per patient per day for dengue and non-dengue patients respectively (p>0.05). Laboratory investigations (haematological, biochemical and imaging) accounted for more than 50% of the total cost. The costs were largely homogenous in all subgroups within or across dengue and non-dengue categories. Excluding dengue upfront by subsidised viral genomic testing may yield overall cost savings for non-dengue patients. Conclusion As non-dengue patients incur a similar cost per day as the dengue patients, confirming dengue diagnosis using subsidised tests for patients presenting in the first three days of fever may be cost-efficient.

Toxoplasmosis is an infection caused by the intracellular protozoan parasite Toxoplasma gondii, and is associated with clinically significant infection in immunocompromised individuals. Vertical transmission during pregnancy can manifest as congenital toxoplasmosis in the neonate, and can have serious consequences. This review aims to describe the modalities for prophylaxis of toxoplasmosis in susceptible populations, and focuses on the following: (1) prophylaxis of congenital toxoplasmosis; (2) prophylaxis of toxoplasmosis in patients with HIV/AIDS; and (3) prophylaxis of toxoplasmosis in transplant recipients.

Purpose The Good Intern Programme (GIP) in Sri Lanka has been implemented to bridge the ’theory to practice gap’ of doctors preparing for their internship. This paper evaluates the impact of a 2-day peer-delivered Acute Care Skills Training (ACST) course as part of the GIP. Study design The ACST course was developed by an interprofessional faculty, including newly graduated doctors awaiting internship (pre-intern), focusing on the recognition and management of common medical and surgical emergencies. Course delivery was entirely by pre-intern doctors to their peers. Knowledge was evaluated by a pre- and post-course multiple choice test. Participants’ confidence (post-course) and 12 acute care skills (pre- and post-course) were assessed using Likert scale-based questions. A subset of participants provided feedback on the peer learning experience. Results Seventeen courses were delivered by a faculty consisting of eight peer trainers over 4 months, training 320 participants. The mean (SD) multiple choice questionnaire score was 71.03 (13.19) pre-course compared with 77.98 (7.7) post-course (p Conclusions A peer-delivered ACST course was extremely well received and can improve newly qualified medical graduates’ knowledge, skills and confidence in managing medical and surgical emergencies. This peer-based model may have utility beyond pre-interns and beyond Sri Lanka.

The mite-borne rickettsial zoonosis scrub typhus is widely prevalent in parts of Southeast and Far East Asia, and northern Australia. The disease is an acute febrile illness, associated with rash and often an eschar, which responds dramatically to treatment with antibiotics. In some cases it results in a serious illness leading to multiple organ involvement and death. The disease manifestations are thought to result from a systemic vasculitis, caused by both direct effects of the organisms as well as an exaggerated immune response, although little is understood about its pathogenesis. A wide spectrum of clinical manifestations, affecting nearly every organ system, have been described with scrub typhus. Some of these manifestations are serious and life threatening. In this systematic review, we summarise the typical and atypical manifestations of scrub typhus reported in the literature. Awareness of these unusual manifestations will hopefully guide clinicians towards diagnosing the condition early, and initiating early appropriate antibiotics and other supportive measures.

Background Although dengue viral infections have emerged as one of the most important mosquito-borne diseases, neurological manifestations of dengue infections are uncommon. Guillain–Barré syndrome and Miller Fisher syndrome have been reported to occur as immune-mediated complications following dengue infection. We report the case of a patient who developed Miller Fisher syndrome during the acute phase of dengue fever suggesting that Miller Fisher syndrome may arise as a result of direct neurotropism of the dengue virus. Case presentation A 70-year-old Sri Lankan man with well-controlled diabetes mellitus and hypertension presented with fever of 3 days’ duration, drooping of eyelids, dysarthria, and unsteady gait. He developed bilateral asymmetric partial ptosis, complete external ophthalmoplegia, bilateral palatal palsy, unilateral tongue weakness, ataxia, and areflexia from the second day of illness. He did not have limb weakness. He had evidence of acute dengue infection including progressive thrombocytopenia and leukopenia, positive dengue non-structural protein 1 antigen, dengue immunoglobulin M antibodies, and polymerase chain reaction detection of dengue virus genome in serum. Magnetic resonance imaging of his brain and cerebrospinal fluid analysis were normal. Polymerase chain reaction for dengue virus and immunoglobulin M antibodies in cerebrospinal fluid were negative. Nerve conduction studies showed axonal neuropathy. Antibodies (immunoglobulin G, immunoglobulin M, and immunoglobulin A) against GQ1b and GT1a were negative. He was treated with intravenously administered immunoglobulins and a recommended fluid regimen for dengue fever. He made a complete recovery from dengue fever in 7 days and Miller Fisher syndrome in 20 days. Conclusions This case report highlights the rare occurrence of Miller Fisher syndrome during the acute phase of dengue fever. Neurological manifestations may occur as a consequence of direct neurotropism of dengue virus.

Leptospirosis is a disease of epidemic proportions in Sri Lanka. There is paucity of data on the determinants of mortality and impact of therapy in patients with leptospirosis admitted to critical care settings in endemic territories.This retrospective cross-sectional study was performed in patients with serologically confirmed leptospirosis admitted to the intensive care unit of the General Hospital, Kalutara from January 2011 to April 2014. Associations between socio-epidemiological, clinical and laboratory parameters and patient mortality were examined.Forty-five patients were included. The mean age was 49.11(SD = 16.95) and majority (92%) were male. Percentage mortality was 44.4%. Patient mortality was associated with age40 (p = 0.012), symptoms of uremia (p = 0.017), evidence of CNS involvement (p = 0.039), presence of oliguria (p = 0.002) and anuria (p = 0.014), presence of multi-organ dysfunction syndrome (MODS) (p0.001), CRP96 (p = 0.036), platelet count20,000 (p = 0.045), Potassium5.0 (p = 0.05), metabolic acidosis with pH7.2 (p = 0.03), INR2 (p = 0.037) and requirement of mechanical ventilation (p0.001). Cox regression analysis revealed MODS and potassium5 to be independently associated with mortality.A high mortality rate is noted. The presence of MODS and serum potassium concentration5.0 was independently associated with mortality in this retrospective study of patients with confirmed leptospirosis in a critical care setting.

Background Takayasu arteritis is a rare large vessel vasculitis which predominantly affects young Asian females. Aortic regurgitation and heart failure are well described manifestations which are usually preceded by constitutional symptoms, limb claudication, pulse and blood pressure discrepancies, vascular bruits and features of organ ischaemia. Case presentation A 25-year- old Sri Lankan female presented with a three days history of acute shortness of breath, cough and orthopnoea. On examination she had severe aortic regurgitation resulting in high output cardiac failure. There was no evidence of acute coronary ischaemia or infective endocarditis. The only significant investigation finding was an elevated erythrocyte sedimentation rate (ESR) of 114 mm/first hour. The patient was treated for pulmonary oedema and empirically for infective endocarditis. Extensive evaluation for an underlying infection, large vessel vasculitis or malignancy did not reveal any abnormalities. Detailed periodic assessment identified reduced blood pressure in left arm (70/40 mmHg) compared to right (100/70 mmHg) and reduced pulse volume of left arm with left subclavian bruit more than one year after the initial presentation. Digital subtraction angiography revealed significant stenosis at first part of left subclavian and origin of left vertebral arteries. A diagnosis of Takayasu arteritis was made and patient was started on high dose glucocorticoids. Conclusions Takayasu arteritis can present initially with isolated cardiac involvement even as acute cardiac manifestations and high degree of suspicion with close follow up would allow early detection of development of other classic features and timely diagnosis.

Background Dengue virus infection in humans can lead to a wide range of clinical manifestations, from mild fever to potentially fatal dengue shock syndrome. The incidence of dengue fever is on the rise in tropical countries. Due to the increasing incidence of dengue fever worldwide, atypical manifestations of the disease are increasingly reported. In this article we report a patient with dengue haemorrhagic fever who presented with reversible splenial lesion syndrome. Case presentation A 24-year-old Sri Lankan man who presented with fever and confusion was eventually diagnosed to have reversible splenial lesion syndrome based on brain imaging. Clinical, serological and haematological parameters confirmed a diagnosis of dengue haemorrhagic fever. His presentation, assessment, and management are described in this case report. Conclusion Reversible splenial lesion syndrome is a condition which is radiologically characterized by reversible lesion in the splenium of the corpus callosum. It is associated with infectious and non-infectious aetiologies. This case report highlights the occurrence of reversible splenial lesion syndrome as a presenting feature of the expanding list of unusual neurological manifestations of dengue infection.

This study was performed to evaluate the prevalence of thickened carotid intima media thickness (CIMT) in a Sri Lankan cohort of lupus nephritis (LN) patients and to identify associations between traditional cardiovascular disease (CVD) and LN-related risk factors with increased CIMT. Consecutive patients with biopsy-proven LN were evaluated for conventional CVD risk factors, renal parameters and extent of organ involvement in this cross-sectional study. Current disease activity and damage were assessed by the British Isles Lupus Activity Group (BILAG) score and the Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) damage index, respectively. CIMT was assessed by B Mode grey scale ultrasonography. Increased CIMT was defined as CIMT more than the 75th percentile based on cutoffs from the "Carotid Atherosclerosis Progression Study." Forty patients (98% female), with a mean age of 38 years (age range of 20-50) and of South Asian descent, were evaluated. The mean duration of disease of 6.15 years (SD = 4.66). The overall prevalence of cardiovascular events was low and included previous acute coronary syndromes in 7.5%, stable angina in 5%, cerebrovascular accidents in 7.5% and transient ischemic attacks in 2.5% of the patients; 72.5% had hypertension (HTN) [mean blood pressure (BP) 140/80 mm Hg]; 32.5% had dyslipidemias (mean serum cholesterol 5.9; SD = 5.6) and 25% had diabetes (mean blood sugar 103.7; SD = 15.6). Forty percent were obese and 20% were overweight (Asian cutoffs). Increased CIMT (57.5%) and atherosclerotic plaques (15.36%) indicated a high CVD risk in this cohort. Diabetes (P = 0.016), HTN (P = 0.002), dyslipidemia (P = 0.002) and obesity (P = 0.048) were associated with thickened CIMT. The only LN-related risk factor associated with thickened CIMT (P

The global incidence of dengue has increased sevenfold between 1990 and 2013. Despite a low case fatality rate (

OBJECTIVES To evaluate the evidence for use of different formulations of amphotericin B (AmB), minimum effective dose for each formulation and its comparative efficacy against other drugs in achieving definitive cure of visceral leishmaniasis. METHODS This systematic review and meta-analysis included following data sources: PubMed, Embase, Scopus, Web of Science and CINAHL. Controlled prospective clinical trials (randomized or nonrandomized, including dose-ranging studies) conducted between 1996 and 2017 with at least one treatment group receiving AmB were included (published data only). The primary outcome was definitive cure at 6 months. Adverse events and mortality were assessed as secondary outcomes. The PROSPERO registration number for this review is CRD42017067488. RESULTS Thirty-one studies (26 from India) that enrolled 6903 patients into 84 study groups met the selection criteria. In India, liposomal AmB was not inferior to AmB deoxycholate (relative risk 1.00, 95% confidence interval (CI) 0.96-1.03, two randomized controlled trials (RCTs), 514 participants, high-quality evidence), and a single dose of the earlier formulation as low as 3.75 mg/kg achieved a cure rate of over 89% (95% CI 70.6-97.2). AmB deoxycholate was as effective as miltefosine (relative risk 0.99, 95% CI 0.95-1.03, two trials, 523 participants, high-quality evidence) and may be better than paromomycin (relative risk 1.04, 95% CI 1.02-1.07, one trial, 667 participants, low-quality evidence) in achieving definitive cure. CONCLUSIONS AmB is an efficacious drug in the Indian subcontinent. Further evidence is needed from prospective clinical trials in other endemic geographical regions.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the efficacy of vector control measures against Ae. albopictus and Ae. aegypti in reducing the incidence of viral infections spread by these mosquito species.

Background Resistant hypertension is defined as an uncontrolled blood pressure despite treatment at best-tolerated doses with at least three antihypertensive agents including a diuretic. It is an emerging public health problem. At present clinical trial data on management of resistant hypertension is limited. Management is largely based on observational studies and expert opinions. Propranolol is a nonselective beta blocker. Several studies have confirmed that propranolol has a significant hypotensive action, both when used alone and as an adjuvant therapy. At present there are no prospective, randomized, clinical studies evaluating the effectiveness of propranolol in patients with resistant hypertension. Therefore, we have designed a prospective randomized trial to evaluate the safety and efficacy of propranolol in patients with resistant hypertension. Methods/design The study will be conducted as a randomized, double-blind, placebo-controlled clinical trial for a period of 3 months. The study has been approved by the Ethics Review Committee of the Faculty of Medicine, University of Colombo. A total of 200 adults with resistant hypertension will be recruited for the study. They will be randomly assigned to the test and placebo groups on a 1:1 ratio. The test group will receive propranolol 40 mg three times a day and the control group will receive an identical placebo capsule. The study drugs will be double blinded to both investigators and subjects. The visits and the evaluations will be done as follows: screening (visit 0), 1 month (visit 1), 2 months (visit 2) and 3 months (visit 3). The primary outcomes of the study is to find a statistically significant difference between the fall in mean systolic and mean diastolic blood pressure measured by ABPM (ambulatory blood pressure monitoring) from baseline between the two groups. Data will be analyzed using SPSS v16. Discussion To our knowledge this is one of the first randomized controlled trials evaluating the effects of propranolol in resistant hypertension. This study will provide the necessary groundwork for future large-scale, multicentered clinical trials. The result, positive or negative, should provide a step change in the evidence guiding current and future policies regarding treatment of resistant hypertension. Trial registration Sri Lanka Clinical Trials Registry, identifier: SLCTR/2016/002. Registered on 27 January 2016; Study protocol version 2.1. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-1863-1) contains supplementary material, which is available to authorized users.