Nipun Lakshitha de Silva

Leukotriene receptor antagonists for chronic urticaria: a systematic review

A significant proportion of patients with chronic urticaria respond inadequately to first line treatment with antihistamines. Leukotreine receptor antagonists (LTRA) are also used for chronic urticaria, although firm recommendations on their use are lacking. We performed a systematic review of randomised trials to determine the role of LTRA in treatment of chronic urticaria. A search of PUBMED, EMBASE, SCOPUS, LILACS, the Cochrane Central Register of Controlled Trials, and the Web of Science for relevant randomized control trials or cross over studies yielded 10 eligible studies. The heterogeneity of trials were high, preventing valid meta-analysis of data. Most trials indicated that LTRA are not superior to placebo or antihistamine therapy, while combination therapy of LTRA and antihistamines appear to be more efficacious compared to antihistamine alone. The side effect profile and tolerability of this group of drugs is acceptable. The use of LTRA as monotherapy cannot be recommended. LTRA are effective add-on therapy to anti-histamines, and their use in patients responding poorly to antihistamines is justifiable. Further well designed randomized controlled trials with clear and standardized outcome measures are needed to determine the role of LTRA in chronic urticaria.

Diagnosis of Leptospirosis: Comparison between Microscopic Agglutination Test, IgM-ELISA and IgM Rapid Immunochromatography Test

Background Leptospirosis is diagnosed on clinical grounds, and confirmed by microscopic agglutination test (MAT). IgM-ELISA (Serion-Virion) and immunochromatography test (Leptocheck-WB) are two immunodiagnostic assays for leptospirosis. Their sensitivity, specificity and applicability in Sri Lanka have not been systematically evaluated. Methods Clinically diagnosed leptospirosis patients (n = 919) were recruited from three hospitals in the Western Province of Sri Lanka, during June 2012 to December 2013. MAT, IgM-ELISA and Leptocheck-WB were performed on all patient sera. MAT titer of ≥400 in single sample, four-fold rise or seroconversion ≥100 in paired samples were considered as positive for MAT. For diagnostic confirmation, MAT was performed during both acute and convalescent phases. Anti-leptospiral IgM ≥20 IU/ml and appearance of a band in the test window were considered as positive for IgM-ELISA and Leptocheck-WB test respectively. Patients with an alternative diagnosis (n = 31) were excluded. Data analysis was performed using two methods, i) considering MAT as reference standard and ii) using Bayesian latent class model analysis (BLCM) which considers each test as imperfect. Results MAT, IgM-ELISA and Leptocheck-WB positivity were 39.8%, 45.8% and 38.7% respectively during the acute phase. Acute-phase MAT had specificity and sensitivity of 95.7% and 55.3% respectively, when compared to overall MAT positivity. IgM-ELISA and Leptocheck-WB had similar diagnostic sensitivity when compared with acute-phase MAT as the gold standard, although IgM-ELISA showed higher specificity (84.5%) than Leptocheck-WB (73.3%). BLCM analysis showed that IgM-ELISA and Leptocheck-WB had similar sensitivities (86.0% and 87.4%), while acute-phase MAT had the lowest sensitivity (77.4%). However, acute-phase MAT had high specificity (97.6%), while IgM-ELISA and Leptocheck-WB showed similar but lower specificity (84.5% and 82.9%). Conclusions Both IgM-ELISA and Leptocheck-WB shows similar sensitivities and specificities. IgM-ELISA may be superior to MAT during the acute phase and suitable for early diagnosis of leptospirosis. Leptocheck-WB is suitable as a rapid immunodiagnostic screening test for resource limited settings.

Changes in full blood count parameters in leptospirosis: a prospective study

Background Leptospirosis presents diagnostic challenges to clinicians, in settings where other acute febrile illness are prevalent. The patterns of serial changes in haematological parameters in leptospirosis has not been evaluated previously. Methods Clinical and laboratory data were collected prospectively from patients with leptospirosis in two hospitals in Sri Lanka. Leptospirosis was diagnosed based on WHO clinical criteria with confirmation using Microscopic Agglutination Test titre > 400 or 4 fold rise between acute and convalescent samples. Full blood count parameters were analysed up to the 14th day of illness. Results Data from 201 patients with leptospirosis were available. Leukocyte counts and absolute neutrophil counts showed a decline over the first 5 days of illness, then rose until the end of the second week. On day 3 of fever, the majority (75%) had normal leukocyte counts, and by day 5, leukocytosis was seen only in 38.1%; leucopenia was an uncommon finding. Lymphopenia was seen in over half on day 5, declining to just under a quarter of patients by day 10. Platelets declined over the first 6 days and then gradually rose. Thrombocytopenia was seen in nearly three-fourths of patients by day 5. Haemoglobin and haematocrit levels declined over the course of illness. Total white cell and neutrophil counts were higher, and haemoglobin and haematorcrit were significantly lower, in patients with severe disease. Conclusions Neither leukocytosis nor lymphopenia were prominent features, while thrombocytopenia was seen during the 3rd to 5th day of illness, with dropping haemoglobin levels. Neutrophilia and low haemoglobin levels appear to predict severe disease. These findings may be of use to clinicians in differentiating leptospirosis from other acute infections like dengue, and could help in predicting severe leptospirosis.

High dose corticosteroids in severe leptospirosis: a systematic review

The role of corticosteroids in the treatment of severe leptospirosis is unclear. The rationale for their use is that, in severe leptospirosis, there is a severe immunological response that is harmful to the host resulting in multi-organ dysfunction, which is potentially offset by the nonspecific immunosuppression of high dose steroids. We conducted a systematic review of studies that have assessed the use of high dose corticosteroids in patients with severe leptospirosis by searching MEDLINE and Scopus SciVerse without any language or time restrictions. We identified five studies, including one open randomized clinical trial, which had assessed the use of high dose steroids in severe leptospirosis. Four studies demonstrated a benefit of corticosteroids in treating severe disease with pulmonary involvement when administered early in the course of the disease, but these studies had several methodological constraints as highlighted in the text. Only the randomized controlled trial study showed that corticosteroids are ineffective and may increase the risk of nosocomial infections. There is no robust evidence to suggest that high dose corticosteroids are effective in severe leptospirosis, and a well-designed randomized clinical trial is needed to resolve this.

Educating the security forces, a high risk group in malaria elimination efforts: an example from Sri Lanka

BACKGROUND The security forces are a high risk group for malaria transmission in Sri Lanka. Interrupting transmission and maintaining surveillance in this group is an important component of elimination efforts. The objective of the study was to develop a prototype educational programme on malaria for security forces serving in endemic areas. METHODS An interactive seminar was designed to deliver the required knowledge. The content was on current status, transmission, signs and symptoms and the role of security personnel in identification and prevention of malaria. Each seminar was preceded by a pre-test and followed by a post test to assess the improvement of knowledge. RESULTS Fifty seminars were held in eight districts over 2 months with 2301 security forces personnel participating. Pre seminar knowledge on malaria was significantly better in the medical corps, those who had completed secondary education and in the Army compared to other security forces (p<0.001). Participation in the seminar resulted in an improvement in all domains tested as shown by test scores in post seminar assessment (p<0.001). CONCLUSIONS Conducting a formal educational programme is an effective strategy to improve awareness on malaria amongst security forces personnel who are a high risk group for re-introduction of malaria into the country.

A Diagnostic Scoring Model for Leptospirosis in Resource Limited Settings

Background Leptospirosis is a zoonotic infection with significant morbidity and mortality. The clinical presentation of leptospirosis is known to mimic the clinical profile of other prevalent tropical fevers. Laboratory confirmation of leptospirosis is based on the reference standard microscopic agglutination test (MAT), direct demonstration of the organism, and isolation by culture and DNA detection by polymerase chain reaction (PCR) amplification. However these methods of confirmation are not widely available in resource limited settings where the infection is prevalent, and reliance is placed on clinical features for provisional diagnosis. In this prospective study, we attempted to develop a model for diagnosis of leptospirosis, based on clinical features and standard laboratory test results. Methods The diagnostic score was developed based on data from a prospective multicentre study in two hospitals in the Western Province of Sri Lanka. All patients presenting to these hospitals with a suspected diagnosis of leptospirosis, based on the WHO surveillance criteria, were recruited. Confirmed disease was defined as positive genus specific MAT (Leptospira biflexa). A derivation cohort and a validation cohort were randomly selected from available data. Clinical and laboratory manifestations associated with confirmed leptospirosis in the derivation cohort were selected for construction of a multivariate regression model with correlation matrices, and adjusted odds ratios were extracted for significant variables. The odds ratios thus derived were subsequently utilized in the criteria model, and sensitivity and specificity examined with ROC curves. Results A total of 592 patients were included in the final analysis with 450 (180 confirmed leptospirosis) in the derivation cohort and 142 (52 confirmed leptospirosis) in the validation cohort. The variables in the final model were: history of exposure to a possible source of leptospirosis (adjusted OR = 2.827; 95% CI = 1.517–5.435; p = 0.001) serum creatinine > 150 micromol/l (adjusted OR = 2.735; 95% CI = 1.374–4.901; p = 0.001), neutrophil differential percentage > 80.0% of total white blood cell count (adjusted OR 2.163; 95% CI = 1.309–3.847; p = 0.032), serum bilirubin > 30 micromol/l (adjusted OR = 1.717; 95% CI 0.938–3.456; p = 0.049) and platelet count < 85,000/mm3 (adjusted OR = 2.350; 95% CI = 1.481–4.513; p = 0.006). Hosmer-Lemeshow test for goodness of fit was 0.931. The Nagelkerke R2 was 0.622. The area under the curve (AUC) was noted as 0.762. A score value of 14 reflected a sensitivity of 0.803, specificity of 0.602, a PPV of 0.54, NPV of 0.84, a positive LR of 2.01 and a negative LR of 0.32. Conclusions The above diagnostic model for diagnosis of leptospirosis is suggested for use in clinical settings. It should be further validated in clinical practice.

Why do doctors emigrate from Sri Lanka? A survey of medical undergraduates and new graduates

BackgroundMigration of medical professionals is a long recognized problem in Sri Lanka, but it has not been studied in depth. Undergraduate and postgraduate medical education in Sri Lanka is state sponsored, and loss of trained personnel is a loss of investment. This study assessed the intention to migrate among medical students and newly passed out graduates from the largest medical school in Sri Lanka.MethodsA cross sectional descriptive study was conducted in the Faculty of Medicine, University of Colombo in September 2013 with the participation of first and fourth year medical students and pre-intern medical graduates. Data was collected using a self administered, pre-tested questionnaire that collected data on socio-demographic details, intention to migrate and factors influencing a decision for or against migration.ResultsThere were 374 respondents, 162 from first year (females; 104, 64.2%), 159 from fourth year (females; 85, 53.5%) and 53 pre interns (females; 22, 41.5%). Of the entire sample, 89 (23.8%) had already decided to migrate while another 121 (32.3%) were not sure of their decision. The most cited reasons for migration were a perceived better quality of life, better earnings and more training opportunities in the host country. There were no socio-demographic characteristics that had a significant association with the intention to migrate, indicating that it is a highly individualized decision.ConclusionsThe rate of intention to migrate in this sample is low when compared to international studies from Africa and South Asia, but is still significant. The core reasons which prompt doctors to migrate should be addressed by a multipronged approach to prevent brain drain.

Prophylaxis of human toxoplasmosis: a systematic review

Abstract 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.

Patient satisfaction and uptake of private-sector run malaria diagnosis clinics in a post-conflict district in Sri Lanka

BackgroundWith the incidence of malaria in Sri Lanka declining, intensive parasitological surveillance has been identified as a key strategy to achieve elimination by end 2014. Tropical and Environmental Diseases and Health Associates Private Limited (TEDHA) in collaboration with the Anti-Malaria Campaign established 43 malaria diagnostic laboratories (MDL) in four post-conflict districts of the Northern and Eastern Provinces. This study assesses the patterns of referral of patients with fever for malaria diagnosis by health care providers (HCPs) in four government hospitals in one of the districts of the Northern Province, and patient satisfaction with the laboratory services offered.MethodsIn this prospective descriptive study, data was collected on the proportion of fever patients being referred by the HCP in hospitals for malaria screening, and the proportion thereof who underwent screening. An interviewer-administered questionnaire was also used to assess patient satisfaction among those attending MDL, which was graded on a scale of 0–4.ResultsOf patients presenting to the hospitals with fever, only 44.3% were referred for malaria screening; 81.7% of them underwent screening. Referral depended largely on the presence of a permanent staff HCP. Satisfaction levels were high, with 86.55% giving an overall rating of 4. Comfort within the laboratory was rated satisfactory in three of the four hospitals.ConclusionsThis study demonstrates the success of a public-private partnership in the malaria control programme in Sri Lanka. Malaria is considered low on the differential diagnosis in patients with fever even in previously malaria-endemic areas, due to the declining incidence of malaria and the increase in other febrile illnesses in these areas during the recent past. Private sector run malaria diagnostic services provided free of charge within government hospitals are viable and effective, and had good patient satisfaction ratings. In a country on the brink of eliminating malaria, there should be further emphasis on ensuring that HCPs refer patients for malaria diagnosis, in order to prevent a resurgence of the disease.

Prophylactic and therapeutic interventions for bleeding in dengue: a systematic review

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.