Search

The efficacy of magnesium sulphate in chronic obstructive pulmonary disease (COPD) was assessed by conducting a systematic review of published randomized clinical trials through extensive searches in MEDLINE and SCOPUS with no date limits, as well as manual review of journals. Outcome measures varied depending on route(s) of administration of magnesium sulphate and medications co-administered. Risk of bias was evaluated and quality of evidence was graded. Four (4) randomized trials were included. All trials had a moderate risk of bias and were of average methodological quality. Magnesium sulphate given intravenously did not seem to have an immediate bronchodilatory effect; however it appears to potentiate the bronchodilatory effect of inhaled beta-2 agonists. Increase in peak expiratory flow rate (PEFR) at 30 and 45 min was greater in those who received magnesium sulphate compared to placebo (P = 0.03), although the mean percentage change in PEFR was just 24%, without significant differences in dyspnoea scores, hospital admission rates, or emergency department readmission rates compared to placebo. Nebulized magnesium sulphate with salbutamol versus nebulized salbutamol with saline placebo showed no significant differences is forced expiratory volume in 1 s (FEV1) measured at 90 min after adjustment for baseline FEV1 (P = 0.34) or differences in the need for hospital admission. Combined inhalational and intravenous magnesium sulphate versus intravenous saline placebo and nebulized ipratropium bromide were comparable in terms of hospital admission, intubation and death, but the ipratropium bromide group showed better bronchodilator effect and improvement in arterial blood gas parameters. Overall, trial evidence for trial evidence for magnesium sulphate in acute exacerbation of COPD is poor, and further well-designed trials are needed. [ABSTRACT FROM AUTHOR]

Background: The Faculty of Medicine, University of Colombo, Sri Lanka, has an integrated curriculum with a Behavioural Sciences Stream (BSS). Objective: Our aim was to assess the perceptions of medical students regarding behavioural sciences learning. Methods: Perceptions regarding the BSS were evaluated among fourth-year students using a selfadministered questionnaire. Results: Of 216 invited, 166 students participated. The majority, i.e., 67% percent agreed that behavioural sciences constitutes an integral component of the curriculum. All (100%) claimed they would give lower priority to behavioural sciences compared to applied sciences. The majority indicated that they would avoid behavioural sciences activities if they were optional, despite 81.8% accepting that the course was beneficial. The majority observed that taught concepts were not effectively practiced in the clinical setting. Small group discussions were considered more effective and enjoyable than lectures, which most thought should be made optional. Although assessments were thought to be appropriate, performance was poorer at behavioural sciences assessments compared to applied sciences. Conclusions: The value of formal behavioural stream training is not fully appreciated. Vertical integration with the clinical curriculum is likely to be more effective strategy for teaching behavioural sciences. [ABSTRACT FROM AUTHOR]

Background: The relationship between inducible nitric oxide synthatase activity and disease severity in leptospirosis is unclear. Nitric oxide is converted to nitrites and nitrates, thus nitrite and nitrate levels (NOx) in serum are considered surrogate markers for nitric oxide. NOx are excreted through the kidneys, and elimination is diminished in renal impairment. We assessed the correlation of NOx with disease severity in patients with leptospirosis, compared with healthy controls and non-leptospirosis fever patients. Methods: All patients admitted over a two-month period to the National Hospital, Colombo, Sri Lanka with a clinical picture suggestive of leptospirosis were included. Leptospirosis was confirmed by the microscopic agglutination test (titre⩾400). Severe leptospirosis was defined by the presence of two or more of the following criteria: jaundice (bilirubin> 51.3 μmol/l), oliguria (urine output < 400 ml/day), serum creatinine> 133 μmol/l or blood urea > 25.5 mmol/l, or the presence of organ dysfunction. Non-leptospirosis fever patients and healthy volunteers were used as control groups. NOx levels were measured using a modified Griess reaction. Results: Forty patients were confirmed as having leptospirosis and 26 of them had severe disease. NOx levels were significantly higher in confirmed leptospirosis patients compared to healthy controls, MAT equivocal patients and non-leptospirosis fever patients (p<0.001). NOx concentrations were also significantly higher in patients with severe compared to mild leptospirosis (p<0.001). Once NOx levels were corrected for renal function, by using the ratio NOx/creatinine, NOx levels were actually significantly lower in patients with severe disease compared to other patients, and values were similar to those of healthy controls. Conclusions: We postulate that high NOx levels may be protective against severe leptospirosis, and that finding low NOx levels (when corrected for renal function) in patients with leptospirosis may predict the development of severe disease and organ dysfunction. [ABSTRACT FROM AUTHOR]

Background Malaria-related knowledge, preventative methods and treatment-seeking behaviours were investigated in a post-conflict district of Sri Lanka in order to guide the development of components of malaria interventions and to support future programme evaluation. Methods A structured questionnaire was used to collect data from a random sample of 300 households in four Divisional Secretariat Divisions (DSD) of the district where internally displaced populations were being resettled after a 30-year civil war. Results The surveyed community had a good overall level of knowledge of malaria. There was high bednet ownership (94.0%), although only 48.0% of households in the study had long-lasting insecticide-treated nets (LLIN). Most respondents reported rapid treatment-seeking behaviour (71.0%) and easy access to malaria diagnostic facilities (67.0%). The Tamil population living in Manthai West and Madhu DSDs who were displaced to refugee camps had better malaria-related knowledge and practices, probably due to the malaria control activities focused on these camps by the government. Conclusions Although knowledge and practices regarding malaria amongst resettled populations in Mannar District were high, continued malaria surveillance, case management, vector control including distribution of LLINs, education and information campaigns are important not only amongst the communities affected by the conflict but the entire district. [ABSTRACT FROM PUBLISHER]

The article examines the patterns of disease conditions and healthcare among the elderly in Sri Lanka. It was found out that more than one-third of the elderly have poor health status. It reports that there is a high prevalence of rheumatological problems and mental health problems among the elderly, such as dementia and depression. It adds that the elderly have at least one chronic medical problem. It recommends the need for establishing a geriatric care training program in Sri Lanka.

The article reports on a study which evaluates the characteristics of morbidity, treatment compliance, and the mental well-being of elderly people admitted to a general medical unit in Sri Lanka. The study shows that the disease was primarily on non-communicable diseases among older people. It notes that social support was satisfactory for the patients, but did not indicate a connection with drug compliance, Mini Mental State Examination (MMSE) and Barthel's Index (BI).

Introduction: The increasing number of women acquiring Human Immunodeficiency Virus (HIV) has resulted in a 'feminization' of the epidemic. In this article we are reviewing whether females are disadvantaged in the epidemic, due to factors independent of the biological differences in sexes. Materials and Methods: We searched MEDLINE and EMBASE for articles with key words 'Women', 'Gender,' and 'HIV' in any field. The search was restricted to articles published in English within the last 10 years (1999-2009). Data were coded independently by two reviewers from 94 selected sources. The coded data were categorized under five commonly encountered concepts; violence, poverty, gender norms, prevention-/treatment-related issues, and Highly Active Anti-Retroviral Treatment (HAART). Results: The link between inter-partner violence (IPV) and HIV risk for women is observed by many authors. In assessing the link between poverty and HIV, indicators such as food insufficiency and income inequality may be better indicators compared to wealth itself. Although women are disadvantaged with male-dominated gender norms, evidence suggests that the traditional norms are changing in many societies. A positive association between living in urban communities, education, and better HIV knowledge has been observed in females, although it is not always synonymous with reduced risk behavior. Conclusions: Women are still disadvantaged in many HIV-related issues such as poverty, violence, and gender norms. At least in Africa, there is evidence of a positive change in spheres of education and gender norms. However, the situation in Asia is largely unexplored. [ABSTRACT FROM AUTHOR]

Background: This review analyses and summarises the recent advances in understanding the neurobiology of violence and empathy, taxonomical issues on defining personality disorders characterised by disregard for social norms, evidence for efficacy of different treatment modalities and ethical implications in defining 'at-risk' individuals for preventive interventions. Methods: PubMed was searched with the keywords 'antisocial personality disorder', 'dissocial personality disorder' and 'psychopathy'. The search was limited to articles published in English over the last 10 years (1999 to 2009) Results: Both diagnostic manuals used in modern psychiatry, the Diagnostic and Statistical Manual published by the American Psychiatric Association and the International Classification of Diseases published by the World Health Organization, identify a personality disorder sharing similar traits. It is termed antisocial personality disorder in the diagnostic and statistical manual and dissocial personality disorder in the International Classification of Diseases. However, some authors query the ability of the existing manuals to identify a special category termed 'psychopathy', which in their opinion deserves special attention. On treatment-related issues, many psychological and behavioural therapies have shown success rates ranging from 25% to 62% in different cohorts. Multisystemic therapy and cognitive behaviour therapy have been proven efficacious in many trials. There is no substantial evidence for the efficacy of pharmacological therapy. Currently, the emphasis is on early identification and prevention of antisocial behaviour despite the ethical implications of defining at-risk children. Conclusions: Further research is needed in the areas of neuroendocrinological associations of violent behaviour, taxonomic existence of psychopathy and efficacy of treatment modalities. [ABSTRACT FROM AUTHOR]

Abstract: Severe sepsis has a high mortality, and both incidence and mortality increases with increasing age. In recent years, several specific therapies have been recommended by guidelines to reduce mortality in severe sepsis. We review the age distribution in the key clinical trials on which these recommendations are made. Many therapeutic strategies have been evaluated, mainly in younger patients, with extrapolation of evidence toward the older population. Specific evidence of benefit in the elderly is present regarding treatment with activated protein C and ventilatory strategies. In view of the pharmacokinetic and pharmacodynamic differences in older people, and the higher incidence of comorbidity in the elderly, there is a need for clinical trials in severe sepsis to specifically include older patients. [Copyright &y& Elsevier]

Cannabis is the most widely used illegitimate substance in the world, and the number of users has increased by 10% over the last decade worldwide. Therefore, it is important to review the evidence on psychoactive properties of cannabis and its possible association with schizophrenia spectrum disorders (SSD). We searched MEDLINE with the key words cannabis and schizophrenia. The search was limited to articles published in English over the last 10 years (1999-2009). Bibliographies of cited literature were also searched. Data sources included reviews published in core clinical journals, cohort studies, interventional studies, case-control studies, cross-sectional analyses and epidemiological data. Results are discussed under 2 topics. Firstly, evidence related to biochemical functioning of cannabinoids and their relationship to endocannabinoid system is discussed briefly. Secondly, the evidence from clinical studies on cannabis, psychosis proneness and SSD are discussed in detail. The discussion is structured to fit in the evidence from results section to 3 plausible hypotheses on cannabis use and SSD. The evidence for and against each hypothesis is discussed. Despite new evidence, the exact relationship between cannabis and SSD is unclear. There is no firm evidence that cannabis causes SSD. The evidence for the argument that schizophrenic patients are attracted to cannabis is also not strong. The most plausible explanation is that cannabis use and psychosis proneness may have synergistic effects in a vulnerable minority. [ABSTRACT FROM AUTHOR]

Background. Poisoning due to deliberate self-harm with the seeds of yellow oleander (Thevetia peruviana) results in significant morbidity and mortality each year in South Asia. Yellow oleander seeds contain highly toxic cardiac glycosides including thevetins A and B and neriifolin. A wide variety of bradyarrhythmias and tachyarrhythmias occur following ingestion. Important epidemiological and clinical differences exist between poisoning due to yellow oleander and digoxin; yellow oleander poisoning is commonly seen in younger patients without preexisting illness or comorbidity. Assessment and initial management. Initial assessment and management is similar to other poisonings. No definite criteria are available for risk stratification. Continuous ECG monitoring for at least 24 h is necessary to detect arrhythmias; longer monitoring is appropriate in patients with severe poisoning. Supportive care. Correction of dehydration with normal saline is necessary, and antiemetics are used to control severe vomiting. Electrolytes. Hypokalemia worsens toxicity due to digitalis glycosides, and hyperkalemia is life-threatening. Both must be corrected. Hyperkalemia is due to extracellular shift of potassium rather than an increase in total body potassium and is best treated with insulin-dextrose infusion. Intravenous calcium increases the risk of cardiac arrhythmias and is not recommended in treating hyperkalemia. Oral or rectal administration of sodium polystyrene sulfonate resin may result in hypokalemia when used together with digoxin-specific antibody fragments. Unlike digoxin toxicity, serum magnesium concentrations are less likely to be affected in yellow oleander poisoning. The effect of magnesium concentrations on toxicity and outcome is not known. Hypomagnesaemia should be corrected as it can worsen cardiac glycoside toxicity. Gastric decontamination. The place of emesis induction and gastric lavage has not been investigated, although they are used in practice. Gastric decontamination by the use of single dose and multiple doses of activated charcoal has been evaluated in two randomized controlled trials, with contradictory results. Methodological differences (severity of poisoning in recruited patients, duration of treatment, compliance) between the two trials, together with differences in mortality rates in control groups, have led to much controversy. No firm recommendation for or against the use of multiple doses of activated charcoal can be made at present, and further studies are needed. Single-dose activated charcoal is probably beneficial. Activated charcoal is clearly safe. Arrhythmia management. Bradyarrhythmias are commonly managed with atropine, isoprenaline, and temporary cardiac pacing in severe cases, although without trial evidence of survival benefit, or adequate evaluation of possible risks. Accelerating the heart rate with atropine or β-adrenergic agents theoretically increases the risk of tachyarrhythmias, and it has been claimed that atropine increases tachyarrhythmic deaths. Further studies are required. Tachyarrhythmias have a poor prognosis and are more difficult to treat. Lidocaine is the preferred antiarrhythmic; the role of intravenous magnesium is uncertain. Digoxin-specific antibody fragments. Digoxin-specific antibody fragments are effective in reverting life-threatening cardiac arrhythmias; prospective observational studies show a beneficial effect on mortality. High cost and lack of availability limit the widespread use of digoxin-specific antibody fragments in developing countries. Conclusions. Digoxin-specific antibody fragments remain the only proven therapy for yellow oleander poisoning. Further studies are needed to determine the place of activated charcoal, the benefits or risks of atropine and isoprenaline, the place and choice of antiarrhythmics, and the effect of intravenous magnesium in yellow oleander poisoning. [ABSTRACT FROM AUTHOR]

Hypomagnesemia is known to occur for a variety of renal, gastrointestinal and other causes, and is often associated with other electrolyte and metabolic disturbances. We present a case of isolated hypomagnesemia in a patient who had been treated with the chemotherapy agent capecitabine. The approach to diagnosis and treatment is discussed. We postulate that capecitabine may cause isolated hypomagnesemia, possibly due to renal magnesium loss. [ABSTRACT FROM PUBLISHER]

Background Cardiac involvement is known to occur in leptospirosis, however, data on the significance of electrocardiographic and echocardiographic findings is very limited. Methods Electrocardiographic and echocardiographic changes were studied in serologically confirmed patients with leptospirosis. Results Of 22 patients, 45% (10) had cardiac symptoms; 59% (13) had abnormalities on the ECG; 90% (9/10) of patients with cardiac symptoms had at least one electrocardiographic abnormality. Echocardiographic abnormalities were seen in 41% (9). Clinical and echocardiographic evidence of myocarditis was seen in two patients, but left ventricular function was preserved. Conclusions Echocardiographic changes may be useful in identifying patients with myocarditis in leptospirosis, especially in symptomatic patients. [ABSTRACT FROM PUBLISHER]

A letter to the editor about a study to determine the characteristics and disease progression in patients admitted with fever and thrombocytopenia to a general medical unit in Sri Lanka is presented.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 < 0.05).Conclusion: Clinical suspicion overestimates the true number of dengue patients. RT-LAMP is a potentially useful low-cost diagnostic tool for dengue diagnosis. Confirmed dengue patients had significantly higher AST levels and lower lymphocyte counts in early disease compared to others. In confirmed dengue patients, younger age and a higher AST level in early infection were associated with subsequent plasma leakage. [ABSTRACT FROM AUTHOR]

Citrate is widely used as an anticoagulant for platelet function tests (PFTs). Due to an intrinsic inhibitory effect of citrate on platelet function, hirudin is used as an alternative. However, studies comparing the effect of these anticoagulants on rotational thromboelastometry (ROTEM) platelet whole blood impedance aggregometry in thrombocytopenic patients are scant. Cross-sectional study was done in 105 patients who entered the critical phase of Dengue hemorrhagic fever with plasma leakage and severe thrombocytopenia (<100 × 109/L). Samples were collected on two consecutive days and considered as a combined data set for analysis, out of which 200 have been included in the data analysis. Platelet count was used from routine full blood count. ROTEM platelet used TRAPTEM assay, which was performed with 3.2% sodium citrate and 525 ATU/ml hirudin anticoagulated blood. Means of all the TRAPTEM parameters were significantly higher in hirudin, compared to citrate samples (p < .05). Significantly higher overall platelet aggregation was observed in hirudinized samples with a significant mean difference (p < .05) compared to citrate in each quartile of platelet count. Higher platelet aggregation was observed with hirudin compared to citrate in ROTEM platelet whole blood impedance aggregometry in thrombocytopenic patients elaborating the importance of using hirudin anticoagulation in PFTs, particularly in patients with severe thrombocytopenia. [ABSTRACT FROM AUTHOR]

The article discusses a study which examined the profile of patients with acute kidney injury (AKI) at a tertiary level nephrology centre in Sri Lanka. Leptospirosis and snakebite envenomation are cited as common aetiologies of AKI. Also discussed are treatment regimens and reasons behind the high mortality rate of AKI patients.

The authors discuss their study investigating electrocardiographic (ECG) changes in patients admitted with alcohol withdrawal. The results revealed that 25 percent patients had chest pain and 35 percent had palpitations. The authors therefore propose that acute coronary events should be suspected in all patients in alcohol withdrawal and that they should be kept under observation with frequent ECG recordings.

A letter to the editor is presented in response to the article "Dengue Haemorrhagic Fever: Diagnosis, Treatment, Prevention and Control," by the World Health Organization (WHO) in the 1997 issue.

This article presents a letter to the editor that describes the results of a study on age bias in clinical trials of Parkinson's Disease treatment.

Background: Leptospirosis is a zoonotic disease caused by Leptospira species. Variations in lipopolysaccharide (LPS) structure in Leptospira are known to be associated with the serovar diversity and antigenicity. Development of immunodiagnostics for early detection of leptospirosis based on immune responses against different pathogenic antigens as well as development of vaccines are important. Hence, this study has assessed the immune response generated against leptospiral LPS and whole antigen preparations of pathogenic and saprophytic Leptospira and specific changes in peritoneal cells was also studied to elucidate the cellular responses associated with immune response of Wistar rats. Methods: During the study, immune response induced by two types of Leptospira antigen preparations of two selected serovars was compared. Changes in the specific peritoneal cell subpopulations following immunizations of rats were analyzed using flow cytometry. Results: Of the two antigen preparations tested, the LPS extract induced a higher IgM immune response as opposed to the sonicated antigen preparation. Of the two serovars tested, L. interrogans serovar Pyrogenes had induced a higher IgM response compared to that by L. biflexa serovar Patoc. Considering the IgG titers, equivalent responses were observed with all four antigen preparations. Significant increases in lymphocytes were observed following immunization with LPS of both serovars. Interestingly, the B2 cell percentages increased significantly during the immunization period. Further, significant correlations were observed with both IgM and IgG responses and percentage of B2 cells in the peritoneal cavity (PC). Conclusion: LPS extract of L. interrogans serovar Pyrogenes induced higher IgM response while the IgG response was equivalent among the four antigen preparations tested. Significant increase of B2 cell percentage in the peritoneal cavity during the immunization reflects the accumulation of B2 cells in the PC which may play considerable role in generating humoral response against Leptospira antigens. [ABSTRACT FROM AUTHOR]

Tetanus is becoming rarer in both industrialized and developing nations due to an effective vaccination program. In 2010, the World Health Organization estimated there was a 93% reduction in newborns dying from tetanus worldwide, compared to the situation in the late 1980s. Due to its rarity, many diagnostic delays occur as physicians may not consider the diagnosis until the manifestations become overt. Without timely diagnosis and proper treatment, severe tetanus is fatal (mortality is also influenced by the comorbidities of the patient). The principles of treating tetanus are: reducing muscle spasms, rigidity and autonomic instability (with ventilatory support when necessary); neutralization of tetanus toxin with human antitetanus immunoglobulin or equine antitetanus sera; wound debridement; and administration of antibiotics to eradicate locally proliferating bacteria at the wound site. It is difficult to conduct trials on different treatment modalities in tetanus due to both logistical and ethical reasons. However, it is imperative that physicians are aware of the best evidence-based treatment strategies currently available to improve the outcome of patients. This review concentrates on analyzing the current evidence on the pharmacological management of tetanus. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: At least a third of dengue patients develop plasma leakage with increased risk of life-threatening complications. Predicting plasma leakage using laboratory parameters obtained in early infection as means of triaging patients for hospital admission is important for resource-limited settings. Methods: A Sri Lankan cohort including 4,768 instances of clinical data from N = 877 patients (60.3% patients with confirmed dengue infection) recorded in the first 96 hours of fever was considered. After excluding incomplete instances, the dataset was randomly split into a development and a test set with 374 (70%) and 172 (30%) patients, respectively. From the development set, five most informative features were selected using the minimum description length (MDL) algorithm. Random forest and light gradient boosting machine (LightGBM) were used to develop a classification model using the development set based on nested cross validation. An ensemble of the learners via average stacking was used as the final model to predict plasma leakage. Results: Lymphocyte count, haemoglobin, haematocrit, age, and aspartate aminotransferase were the most informative features to predict plasma leakage. The final model achieved the area under the receiver operating characteristics curve, AUC = 0.80 with positive predictive value, PPV = 76.9%, negative predictive value, NPV = 72.5%, specificity = 87.9%, and sensitivity = 54.8% on the test set. Conclusion: The early predictors of plasma leakage identified in this study are similar to those identified in several prior studies that used non-machine learning based methods. However, our observations strengthen the evidence base for these predictors by showing their relevance even when individual data points, missing data and non-linear associations were considered. Testing the model on different populations using these low-cost observations would identify further strengths and limitations of the presented model. Author summary: Current machine learning approaches are mostly designed for decision support systems that used for predicting severity of dengue and forecasting of dengue cases. The few studies to predict plasma leakage rely on traditional statistical approach with a priori predictors. To our knowledge, no study used machine learning to predict plasma leakage in suspected dengue patients. This is the first study to develop a machine learning model to identify predictors that detect plasma leakage in the early stages of dengue infection. In addition, this study placed focus on a limited resource setting enabling decision support systems to be utilised in the low- to middle-income country of Sri Lanka. The study identified five accessible predictors as inputs to the model to aid the decision making for hospital admission for suspected cases of dengue. Lastly, the multi-metric assessments, model fairness and Shapley additive explanations push the agenda for model transparency and interpretability. Our machine learning approach demonstrated reasonable performance and has the potential to identify patients who are likely to develop plasma leakage for close monitoring to prevent severe consequences. [ABSTRACT FROM AUTHOR]

Given the structural similarity between Zika and dengue viruses, prior infection from one virus is hypothesized to modulate the severity of a subsequent infection from the other virus. A previous paediatric cohort study observed that a prior Zika infection may increase the risk of a subsequent symptomatic or severe dengue infection. The Colombo Dengue study is a prospective hospital-based cohort study in Sri Lanka that recruits symptomatic adult dengue patients within the first three days of fever. Anti-Dengue Envelope and anti-Zika NS1 IgG antibodies were tested by ELISA (Euroimmun, Lubeck, Germany) in all recruited patients. Associations between pre-morbid seroprevalence for either or both infections and adverse clinical outcomes of the current dengue infection were explored. A total of 507 dengue infected patients were assessed of whom 342 (68%) and 132 (26%) patients had anti-dengue IgG and anti-Zika IgG respectively. People with combined prior dengue and zika exposure as well as prior dengue exposure alone, were at increased risk of plasma leakage, compensated and uncompensated shock, and severe dengue (p < 0·05), compared to people without prior exposure to either infection. The effect of prior Zika exposure alone could not be established due to the small the number of primary dengue infections with prior Zika exposure. [ABSTRACT FROM AUTHOR]

Introduction: Data on caregiver strain and depression of principal caregivers of patients with mental illnesses are few in developing countries. Findings from developed countries cannot be applied directly to developing countries as culture specific factors may influence the outcome. Methods: A prospective study was carried out in the University Psychiatry Unit of the National Hospital of Sri Lanka (NHSL) to identify symptoms of depression, caregiver strain and dissatisfaction with life in caregivers of patients with schizophrenia and bipolar affective disorder. Participants were assessed using the Center for Epidemiological Studies - Depression Scale, Satisfaction with Life Scale and the Modified Caregiver Strain Index. Results and discussion: Eighty caregivers were interviewed (males; 36, 45%). Symptoms of depression were significant in 37.5%, while 48.8% had unsatisfactory scores on the Satisfaction with Life Scale. Depression and higher caregiver strain were associated with spending more time with the patient, interruption to work, disputes with relations, being assaulted by patient and self admission of needing professional help to overcome mental stress. Conclusion: This study identified several associations for depression and increased caregiver strain among caregivers in a subset of patients with mental disorder in Sri Lanka. These can be used as markers to screen and increase pretest probability to identify caregivers needing help rather than applying the cumbersome questionnaires to all. [ABSTRACT FROM AUTHOR]

Plasma leakage is a precursor to life-threatening complications of dengue, but this group is poorly defined and not often reported in literature. Patients with Dengue haemorrhagic fever (DHF) as defined in the 1997 World Health Organization classification are often reported, and they all have plasma leakage, but some patients with plasma leakage do not meet the definition of DHF. The study aims to estimate the frequency of plasma leakage and DHF (as a surrogate of plasma leakage) in dengue and its variations based on virus serotype, geography, patient gender and pre-existing immunity to dengue. PUBMED, Scopus, EMBASE, CINAHL and Web of Science were searched for prospective observational studies reporting on plasma leakage or DHF. Quality of data was assessed using the NIH quality assessment tool for cohort studies. Forty-three studies that recruited 15,794 confirmed dengue patients were eligible. Cumulative frequency of plasma leakage was 36.8% (15 studies, 1642/4462, 95% CI 35.4-38.2%), but surprisingly the estimated cumulative frequency of DHF was higher (45.7%, 32 studies, 4758/10417, 95% CI 44.7-46.6%), indicating that current medical literature over-reports DHF or under-reports plasma leakage. Therefore, a reliable estimate for the proportion of dengue patients developing plasma leakage cannot be derived from existing medical literature even after applying rigorous inclusion criteria to select homogenous studies. Plasma leakage is an important marker of "at-risk" dengue patients and standardizing its definition, diagnosis and reporting should be a priority in research and global policy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: To compare the traditional haematocrit‐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 haematocrit 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 haematocrit rise >20%. Those positive on ultrasonography were also likely to fulfil the haematocrit‐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 <97 000/µl, AST/ALT > 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 haematocrit 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. [ABSTRACT FROM AUTHOR]

• Confirmatory laboratory diagnosis of leptospirosis is a major challenge. • In-house ELISAs were established to detect anti-leptospiral antibodies. • Factors responsible for the manifestation of severe leptospirosis forms are unclear. • High anti-leptospiral IgG was observed in severe leptospirosis patients compared to mild leptospirosis patients. • Anti-leptospiral IgG could be used as a biomarker to predict disease severity. Leptospirosis is most often diagnosed clinically, and a laboratory test with high diagnostic accuracy is required. IgM and IgG ELISAs using Leptospira antigens were established and evaluated in relation to the microscopic agglutination test (MAT). Antigen preparation consisted of saprophytic Leptospira biflexa to detect genus-specific antibodies (genus-specific ELISA) and a pool of the five most prevalent Leptospira interrogans serovars in Sri Lanka to detect serovar-specific antibodies (serovar-specific ELISA). IgM and IgG immune responses were studied in severe and mild leptospirosis patients (n = 100 in each group). The ELISAs showed high repeatability and reproducibility. The serovar-specific IgM-ELISA showed a sensitivity of 80.2% and specificity of 89%; the genus-specific IgM-ELISA showed a sensitivity of 83.3% and specificity of 91%. The serovar- and genus-specific IgG-ELISAs showed sensitivities of 73.3% and 81.7%, respectively, and specificities of 83.3% and 83.3%, respectively. The commercial IgM-ELISA showed a sensitivity of 79.2% and specificity of 93%. The commercial IgG-ELISA showed a sensitivity of 50% and specificity of 96.7%. IgM levels observed in mild and severe leptospirosis patients were significantly higher than in the healthy control group, with mean absorbance values of 0.770, 0.778, and 0.163, respectively. Severe leptospirosis patients had significantly higher mean anti-leptospiral IgG levels compared to both mild leptospirosis patients and healthy control group subjects (0.643, 0.358, and 0.116, respectively; ANOVA, p < 0.001). The presence of anti-leptospiral IgG above an optical density of 0.643 at 1:100 could predict a high risk of severe disease. The serovar-specific in-house ELISA could be used for the laboratory diagnosis of leptospirosis in endemic settings. The high levels of anti-leptospiral IgG observed suggest its value as a predictor of disease severity. [ABSTRACT FROM AUTHOR]

We present a patient with severe hypothyroidism complicated by paralytic ileus and acute kidney injury. A 65 year old male patient, diagnosed with hypothyroidism one year ago was transferred to our unit in a state of drowsiness and confusion. He was severely hypothyroid and had paralytic ileus and impaired renal function at the time of transfer. Hypokalaemia was present, and was likely to have contributed to the paralytic ileus and this together with dehydration was likely to have contributed to renal injury. Nonetheless, hypothyroidism is very likely to have been the principal precipitant of both these complications, and both paralytic ileus and acute kidney injury improved with thyroxine replacement. Unfortunately, the patient died unexpectedly eight days after admission to the unit. Hypothyroidism may induce de novo acute kidney injury or it may exacerbate ongoing chronic kidney disease. This rare complication is assumed to be due to the hypodynamic circulatory state created by thyroid hormone deficiency. Paralytic ileus is an even rarer fatal manifestation of hypothyroidism and is thought to be due to an autonomic neuropathy affecting the intestines that is reversible with thyroxine replacement. To our knowledge, both these complications have not been observed in a single patient so far. It is important that clinicians are aware of these rare manifestations of hypothyroidism as in most occasions, thyroxine deficiency may be missed, and treatment can reverse the complications. [ABSTRACT FROM AUTHOR]

Post-chikungunya joint pain (arthritis or arthralgia) is a clinical concern in endemic regions as it may cause a debilitating illness sometimes years after the acute infection. This systematic review analyses evidence from controlled clinical trials regarding the efficacy of pharmacological and non-pharmacological interventions to treat post-chikungunya joint pain. PubMed, EMBASE, Scopus, Cochrane library and Web of Science were searched for eligible studies without any language or time limits, excluding retrospective studies, and prospective observational studies without a control group. Eleven studies met the inclusion criteria. Seven assessed pharmacological interventions and four assessed non-pharmacological interventions (exercise, neuromodulation). The number of participants in each intervention arm varied from 10 to 75 and, given the heterogeneity of interventions, a meta-analysis was not possible. Available evidence does not show any added benefit of chloroquine, hydroxychloroquine, stand-alone methotrexate or ribavirin compared with anti-inflammatory drugs or placebo/no treatment. Non-steroidal anti-inflammatory drugs may reduce pain up to 24 wk of treatment but long-term residual impact after stopping treatment is unassessed. Currently, there is also no high certainty evidence to recommend non-pharmacological methods such as exercise and neuromodulation., (© The Author(s) 2022. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

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  < .05). Area under the curve of thrombin receptor activating peptide-6 assay of ROTEM platelet (TRAPTEM) discriminated patients with bleeding manifestations from those without, at a cutoff value of <12.5 Ω*min at a sensitivity and specificity of 73.7%, and 60.2%. In patients who developed bleeding, the maximum lysis of extrinsic pathway of ROTEM was significantly lower in patients with severe bleeding compared to those with mild to moderate bleeding. (4.3 ± 3.4% vs 9.4 ± 7.5%; P  = .01)., Conclusion: An association with bleeding manifestations and TRAPTEM suggest a potential role for defective platelet aggregation in the pathogenesis of bleeding in the critical phase of dengue., (© 2022 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).)

Leptospirosis is one of the most important zoonotic bacterial diseases worldwide, commonly affecting resource-poor populations and resulting in significant morbidity and mortality. This article provides an overview of the epidemiology, clinical manifestations, diagnosis and treatment of human leptospirosis., (© Royal College of Physicians 2022. All rights reserved.)

Background: Chemoprophylaxis is an effective tool for individuals to minimize their risk of contracting malaria and serves an important public health role in preventing imported malaria. Yet, it is only effective if the traveller is fully compliant with the prescribed regimen. For many destinations, a choice of prophylactic agents is available, so historical compliance data can be helpful for both physicians and travellers to make an informed decision., Methods: We analyzed the historical self-reported compliance data for six chemoprophylactic agents currently recommended by CDC for primary malaria chemoprophylaxis by searching PubMed, Embase, CINAHL, Web of Science, and Scopus for observational studies reporting on travelers within the last 25 years. The quality of data was graded as "good" or "poor" using the NIH quality assessment tool for cohort and cross-sectional studies. Cumulative compliance data were compiled for all studies (gross compliance) and the subgroup of studies with "good" quality evidence (refined compliance). Subgroup analyses were performed for weekly vs daily administered regimens, between military and civilian travelers, and across each prophylactic agent., Results: Twenty-four eligible studies assessed compliance for mefloquine (n=20), atovaquone-proguanil (n=11), doxycycline (n=13), and chloroquine (n=3). No studies were found for primaquine or tafenoquine. Both gross and refined compliance were significantly better for weekly regimens than daily regimens ( P <0.0001). Stopping chemoprophylaxis due to adverse events was significantly more for doxycycline ( P <0.0001) compared to other drugs. Compliance was significantly worse in military travelers, but they were also more likely to be prescribed doxycycline., Conclusion: Malaria chemoprophylaxis for a traveler should depend on prevailing resistance patterns at destination, current national guidelines, and patient preferences. However, when there is a choice, historical compliance data are useful to select a regimen that the traveler is more likely to comply with., Competing Interests: The authors have no competing interests to declare., (© 2020 Rodrigo et al.)

Background: Plasmodium vivax malaria has a persistent liver stage that causes relapse of the disease and continued P vivax transmission. Primaquine (PQ) is used to clear the liver stage of the parasite, but treatment is required for 14 days. Primaquine also causes haemolysis in people with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Tafenoquine (TQ) is a new alternative to PQ with a longer half-life and can be used as a single-dose treatment., Objectives: To assess the effects of tafenoquine 300 mg (single dose) on preventing P vivax relapse., Search Methods: We searched the following up to 3 June 2020: the Cochrane Infectious Diseases Group Specialized Register; CENTRAL; MEDLINE; Embase; and three other databases. We also searched the WHO International Clinical Trial Registry Platform and the metaRegister of Controlled Trials for ongoing trials using "tafenoquine" and "malaria" as search terms up to 3 June 2020., Selection Criteria: Randomized controlled trials (RCTs) that gave TQ to prevent relapse in people with P vivax malaria. We planned to include trials irrespective of whether participants had been screened for G6PD enzyme deficiency., Data Collection and Analysis: All review authors independently extracted data and assessed risk of bias. As true relapse and reinfection are difficult to differentiate in people living in endemic areas, studies report "recurrences" of infection as a proxy for relapse. We carried out meta-analysis where appropriate, and gave estimates as risk ratios (RR) with 95% confidence intervals (CI). We assessed the certainty of the evidence using the GRADE approach., Main Results: Three individually randomized RCTs met our inclusion criteria, all in endemic areas, and thus reporting recurrence. Trials compared TQ with PQ or placebo, and all participants received chloroquine (CQ) to treat the asexual infection). In all trials, pregnant and G6PD-deficient people were excluded. Tafenoquine 300 mg single dose versus no treatment for relapse prevention Two trials assessed this comparison. TQ 300 mg single dose reduces P vivax recurrences compared to no antihypnozoite treatment during a six-month follow-up, but there is moderate uncertainty around effect size (RR 0.32, 95% CI 0.12 to 0.88; 2 trials, 504 participants; moderate-certainty evidence). In people with normal G6PD status, there is probably little or no difference in any type of adverse events (2 trials, 504 participants; moderate-certainty evidence). However, we are uncertain if TQ causes more serious adverse events (2 trials, 504 participants; very low-certainty evidence). Both RCTs reported a total of 23 serious adverse events in TQ groups (One RCT reported 21 events) and a majority (15 events) were a drop in haemoglobin level by > 3g/dl (or >30% reduction from baseline). Tafenoquine 300 mg single dose versus primaquine 15 mg/day for 14 days for relapse prevention Three trials assessed this comparison. There is probably little or no difference between TQ and PQ in preventing recurrences (proxy measure for relapse) up to six months of follow-up (RR 1.04, 95% CI 0.8 to 1.34; 3 trials, 747 participants; moderate-certainty evidence). In people with normal G6PD status, there is probably little or no difference in any type of adverse events (3 trials, 747 participants; moderate-certainty evidence). We are uncertain if TQ can cause more serious adverse events compared to PQ (3 trials, 747 participants; very low-certainty evidence). Two trials had higher point estimates against TQ while the other showed the reverse. Most commonly reported serious adverse event in TQ group was a decline in haemoglobin level (19 out of 29 events). Some other serious adverse events, though observed in the TQ group, are unlikely to be caused by it (Hepatitis E infection, limb abscess, pneumonia, menorrhagia)., Authors' Conclusions: TQ 300 mg single dose prevents relapses after clinically parasitologically confirmed P vivax malaria compared to no antihypnozoite treatment, and with no difference detected in studies comparing it to PQ to date. However, the inability to differentiate a true relapse from a recurrence in the available studies may affect these estimates. The drug is untested in children and in people with G6PD deficiency. Single-dose treatment is an important practical advantage compared to using PQ for the same purpose without an overall increase in adverse events in non-pregnant, non-G6PD-deficient adults., (Copyright © 2020 The Authors. Cochrane Database of Systematic Reviews published by John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration.)

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<0.0001; Nagelkerke R2 = 0.546). High risk occupational exposure was determined to be independently associated with seropositivity. Baseline community MAT titres vary according to serovar, and presumably the locality. Testing against saprophytic serovars is unreliable. Thus, diagnostic MAT titre cut-offs should be determined based on region and serovar, and the use of a single diagnostic MAT cut-off for all populations is likely to result in false negatives., Competing Interests: The authors have declared that no competing interests exist.

Background: Elevated blood pressure incurs a major health and economic burden, particularly in low-income and middle-income countries. The Triple Pill versus Usual Care Management for Patients with Mild-to-Moderate Hypertension (TRIUMPH) trial showed a greater reduction in blood pressure in patients using fixed-combination, low-dose, triple-pill antihypertensive therapy (consisting of amlodipine, telmisartan, and chlorthalidone) than in those receiving usual care in Sri Lanka. We aimed to assess the cost-effectiveness of the triple-pill strategy., Methods: We did a within-trial (6-month) and modelled (10-year) economic evaluation of the TRIUMPH trial, using the health system perspective. Health-care costs, reported in 2017 US dollars, were determined from trial records and published literature. A discrete-time simulation model was developed, extrapolating trial findings of reduced systolic blood pressure to 10-year health-care costs, cardiovascular disease events, and mortality. The primary outcomes were the proportion of people reaching blood pressure targets (at 6 months from baseline) and disability-adjusted life-years (DALYs) averted (at 10 years from baseline). Incremental cost-effectiveness ratios were calculated to estimate the cost per additional participant achieving target blood pressure at 6 months and cost per DALY averted over 10 years., Findings: The triple-pill strategy, compared with usual care, cost an additional US$9·63 (95% CI 5·29 to 13·97) per person in the within-trial analysis and $347·75 (285·55 to 412·54) per person in the modelled analysis. Incremental cost-effectiveness ratios were estimated at $7·93 (95% CI 6·59 to 11·84) per participant reaching blood pressure targets at 6 months and $2842·79 (-28·67 to 5714·24) per DALY averted over a 10-year period., Interpretation: Compared with usual care, the triple-pill strategy is cost-effective for patients with mild-to-moderate hypertension. Scaled up investment in the triple pill for hypertension management in Sri Lanka should be supported to address the high population burden of cardiovascular disease., Funding: Australian National Health and Medical Research Council., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

The global incidence of dengue has increased sevenfold between 1990 and 2013. Despite a low case fatality rate (<1%), during epidemics, due to the large number of people affected, overall mortality rates can be significant. The risk of clinically significant bleeding in dengue is unpredictable and often contributes to an adverse outcome. This systematic review focuses on the evidence for prophylactic and therapeutic interventions for bleeding in dengue infection. PubMed, CINAHL, Cochrane Library, Embase and Google Scholar were searched for randomized, quasi-randomized and non-randomized, prospective or retrospective studies that had a control group alongside an intervention aimed at stopping or preventing bleeding in dengue infection. Eleven studies that included 1904 patients in 12 study arms were eligible. These assessed the role of platelet transfusion [two randomized controlled trials (RCTs) and three non-randomized studies], plasma transfusion (one RCT), recombinant activated factor VII (one RCT), anti-D globulin (two RCTs), immunoglobulin (one RCT) and interleukin 11 (one RCT) as prevention or treatment for bleeding. Due to significant heterogeneity in study design and outcome reporting, a meta-analysis was not performed. Currently there is no evidence that any of the above interventions would have a beneficial effect in preventing or treating clinically significant bleeding in dengue., (© The Author(s) 2018. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (© The Author 2017. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Rituximab is a B-cell depleting monoclonal antibody that is gaining popularity as an effective therapy for many autoimmune cytopenias. This article systematically evaluates its therapeutic efficacy in the treatment of different types of autoimmune haemolytic anaemia. We conclude that there is sufficient evidence to recommend it as a second line therapy for warm autoimmune haemolytic anaemia (wAIHA) either as monotherapy or combined therapy. Evidence from a single randomized controlled trial suggests that it may also be more efficacious as first line therapy in combination with steroids than steroids alone. A fewer number of studies have assessed its role in cold autoimmune haemolytic anaemia (cAIHA) and cold agglutinin disease (CAD) with success rates varying from 45-66%. In the absence of alternative definitive therapy, rituximab should be considered for patients with symptomatic CAD and significant haemolysis. Case reports of its efficacy in mixed autoimmune haemolytic anaemias are available but evidence from case series or larger cohorts are nonexistent., (© 2014 The British Pharmacological Society.)