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Chaturaka Rodrigo,1 Senaka Rajapakse,2 Sumadhya Deepika Fernando3 1Department of Pathology, School of Medical Sciences, UNSW, Sydney, NSW, Australia; 2Department of Clinical Medicine, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka; 3Department of Parasitology, Faculty of Medicine, University of Colombo, Colombo, Sri LankaCorrespondence: Chaturaka RodrigoDepartment of Pathology, School of Medical Sciences, University of New South Wales (UNSW), 207, Wallace Wurth Building, Sydney 2052, NSW, AustraliaTel +61 2 9065 2186Email c.rodrigo@unsw.edu.auBackground: 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.Keywords: malaria, prophylaxis, compliance, mefloquine, doxycycline, atovaquone-proguanil

Senaka Rajapakse,1 Chaturaka Rodrigo,1 Sachith Maduranga,1 Anoja Chamarie Rajapakse21Department of Clinical Medicine, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka; 2Kings Mill Hospital, Sherwood Forest NHS Foundation Trust, Sutton-in-Ashfield, Nottinghamshire, UKAbstract: Dengue infection causes significant morbidity and mortality in over 100 countries worldwide, and its incidence is on the rise. The pathophysiological basis for the development of severe dengue, characterized by plasma leakage and the “shock syndrome” are poorly understood. No specific treatment or vaccine is available, and careful monitoring and judicious administration of fluids forms the mainstay of management at present. It is postulated that vascular endothelial dysfunction, induced by cytokine and chemical mediators, is an important mechanism of plasma leakage. Although corticosteroids are potent modulators of the immune system, their role in pharmacological doses in modulating the purported immunological effects that take place in severe dengue has been a subject of controversy. The key evidence related to the role of corticosteroids for various manifestations of dengue are reviewed here. In summary, there is currently no high-quality evidence supporting the beneficial effects of corticosteroids for treatment of shock, prevention of serious complications, or increasing platelet counts. Non-randomized trials of corticosteroids given as rescue medication for severe shock have shown possible benefit. Nonetheless, the evidence base is small, and good-quality trials are lacking. We reiterate the need for well-designed and adequately powered randomized controlled trials of corticosteroids for the treatment of dengue shock.Keywords: dengue, dengue shock, shock, corticosteroids, vascular leak, thrombocytopenia

Senaka Rajapakse,1,2 Chaturaka Rodrigo,1 Anoja Rajapakse31Department of Clinical Medicine, Faculty of Medicine, University of Colombo, Sri Lanka; 2Lincoln County Hospital, United Lincolnshire NHS Trust, Lincoln, UK; 3Kings Mill Hospital, Sherwood Forest NHS Foundation Trust, Mansfield, UKAbstract: The endemic area for dengue fever extends over 60 countries, and approximately 2.5 billion people are at risk of infection. The incidence of dengue has multiplied many times over the last five decades at an alarming rate. In the endemic areas, waves of infection occur in epidemics, with thousands of individuals affected, creating a huge burden on the limited resources of a country's health care system. While the illness passes off as a simple febrile episode in many, a few have a severe illness marked by hypovolemic shock and bleeding. Iatrogenic fluid overload in the management may further complicate the picture. In this severe form dengue can be fatal. Tackling the burden of dengue is impeded by several issues, including a lack of understanding about the exact pathophysiology of the infection, inability to successfully control the vector population, lack of specific therapy against the virus, and the technical difficulties in developing a vaccine. This review provides an overview on the epidemiology, natural history, management strategies, and future directions for research on dengue, including the potential for development of a vaccine.Keywords: dengue, treatment, fluid resuscitation

Shock syndrome is a dangerous complication of dengue infection and is associated with high mortality. Severe dengue occurs as a result of secondary infection with a different virus serotype. Increased vascular permeability, together with myocardial dysfunction and dehydration, contribute to the development of shock, with resultant multiorgan failure. The onset of shock in dengue can be dramatic, and its progression relentless. The pathogenesis of shock in dengue is complex. It is known that endothelial dysfunction induced by cytokines and chemical mediators occurs. Diagnosis is largely clinical and is supported by serology and identification of viral material in blood. No specific methods are available to predict outcome and progression. Careful fluid management and supportive therapy is the mainstay of management. Corticosteroids and intravenous immunoglobulins are of no proven benefit. No specific therapy has been shown to be effective in improving survival.

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.

Background : Severe leptospirosis requires critical care and has a high mortality. We reviewed the literature to identify factors predicting mortality, and such predictors were classified according to the predisposition, infection, response, organ dysfunction (PIRO) concept, which is a risk stratification model used in severe sepsis. Material and Methods : PUBMED was searched for all articles (English), with the key word "leptospirosis" in any field, within the last 20 years. Data were collected from 45 relevant papers and grouped into each component of the PIRO model. Results : The following correlated with increased mortality: predisposition - increasing age and chronic alcoholism; infection - leptospiraemic burden; response - hemodynamic disturbances, leukocytosis; organ dysfunction - multiple organ dysfunction syndrome, pulmonary involvement and acute renal failure. Conclusions : Further research is needed to identify the role of infecting serovars, clinical signs, inflammatory markers, cytokines and evidence of hepatic dysfunction as prognostic indicators. It is hoped that this paper will be an initiative to create a staging system for severity of leptospirosis based on the PIRO model with an added component for treatment-related predictors.

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.

Acute renal failure (ARF) is a common complication of sepsis and carries a high mortality. Renal replacement therapy (RRT) during the acute stage is the mainstay of therapy. Va-rious modalities of RRT are available. Continuous RRT using convective methods are preferred in sepsis-induced ARF, especially in hemodynamically unstable patients, although clear evidence of benefit over intermittent hemodialysis is still not available. Peritoneal dialysis is clearly inferior, and is not recommended. Early initiation of RRT is probably advantageous, although the optimal timing of dialysis is yet unknown. Higher doses of RRT are more likely to be beneficial. Use of bio-compatible membranes and bicarbonate buffer in the dialysate are preferred. Anticoagulation during dialysis must be carefully adjusted and monitored.

Sepsis is an important cause of morbidity and mortality. Acute Kidney Injury (AKI) often complicates sepsis, leading to greater complexity, higher cost of care and worsening prog-nosis. Despite the improved understanding of its underlying pathophysiological basis, there have been very few interventions, which have consistently been shown to be of value in the manage-ment of sepsis-induced AKI. Measures such as adequate hydration, maintenance of adequate circulating blood volume and mean arterial pressure, and avoidance of nephrotoxins, are still the mainstay of prevention. Loop diuretics, mannitol and "low dose" dopamine have been clearly shown to be of no value in the prevention or treatment of AKI and may, in fact, do harm. Among the remaining pharmacological options, N-acetylcysteine (NAC) may have a role in the preven-tion of radiocontrast induced AKI.

Abstract 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 Primaquine was officially licensed as an anti-malarial drug by the FDA in 1952. It has remained the only FDA licensed drug capable of clearing the intra-hepatic schizonts and hypnozoites of Plasmodium vivax. This update and review focuses on five major aspects of primaquine use in treatment of vivax malaria, namely: a) evidence of efficacy of primaquine for its current indications; b) potential hazards of its widespread use, c) critical analysis of reported resistance against primaquine containing regimens; d) evidence for combining primaquine with artemisinins in areas of chloroquine resistance; and e) the potential for replacement of primaquine with newer drugs.

Abstract Background Complaints of arms, neck and shoulders (CANS) is common among computer office workers. We evaluated an aetiological model with physical/psychosocial risk-factors. Methods We invited 2,500 computer office workers for the study. Data on prevalence and risk-factors of CANS were collected by validated Maastricht-Upper-extremity-Questionnaire. Workstations were evaluated by Occupational Safety and Health Administration (OSHA) Visual-Display-Terminal workstation-checklist. Participants' knowledge and awareness was evaluated by a set of expert-validated questions. A binary logistic regression analysis investigated relationships/correlations between risk-factors and symptoms. Results Sample size was 2,210. Mean age 30.8 ± 8.1 years, 50.8% were males. The 1-year prevalence of CANS was 56.9%, commonest region of complaint was forearm/hand (42.6%), followed by neck (36.7%) and shoulder/arm (32.0%). In those with CANS, 22.7% had taken treatment from a health care professional, only in 1.1% seeking medical advice an occupation-related injury had been suspected/diagnosed. In addition 9.3% reported CANS-related absenteeism from work, while 15.4% reported CANS causing disruption of normal activities. A majority of evaluated workstations in all participants (88.4%,) and in those with CANS (91.9%) had OSHA non-compliant workstations. In the binary logistic regression analyses female gender, daily computer usage, incorrect body posture, bad work-habits, work overload, poor social support and poor ergonomic knowledge were associated with CANS and its' severity In a multiple logistic regression analysis controlling for age, gender and duration of occupation, incorrect body posture, bad work-habits and daily computer usage were significant independent predictors of CANS Conclusions The prevalence of work-related CANS among computer office workers in Sri Lanka, a developing, South Asian country is high and comparable to prevalence in developed countries. Work-related physical factors, psychosocial factors and lack of awareness were all important associations of CANS and effective preventive strategies need to address all three areas.

Abstract Background Complaints of arm, neck and/or shoulders (CANS) affects millions of computer office workers. However its prevalence and associated risk factors in developing countries are yet to be investigated, due to non availability of validated assessment tools for these countries. We evaluated the 1-year prevalence of CANS among computer office workers in Sri Lanka and tested the psychometric properties of a translated risk factor questionnaire. Methods Computer office workers at a telecommunication company in Sri Lankan received the Sinhalese version of the validated Maastricht Upper Extremity Questionnaire (MUEQ). The 94 items in the questionnaire covers demographic characteristics, CANS and evaluates potential risk factors for CANS in six domains. Forward and backward translation of the MUEQ was done by two independent bi-lingual translators. One-year prevalence of CANS and psychometric properties of the Sinhalese questionnaire were investigated. Results Response rate was 97.7% (n = 440). Males were 42.7%. Mean age was 38.2 ± 9.5 years. One-year prevalence of CANS was 63.6% (mild-53.7% and severe-10%). The highest incidences were for neck (36.1%) and shoulder (34.3%) complaints. Two factors for each domain in the scale were identified by exploratory factor analysis (i.e. work-area, computer-position, incorrect body posture, bad-habits, skills and abilities, decision-making, time-management, work-overload, work-breaks, variation in work, work-environment and social-support). Calculation of internal consistency (Cronbach's alpha 0.43-0.82) and cross-validation provided evidence of reliability and lack of redundancy of items. Conclusion One year prevalence of CANS in the study population corresponds strongly with prevalence in developed countries. Translated version of the MUEQ has satisfactory psychometric properties for it to be used to assess work-related risk factors for development of CANS among Sri Lankan computer office workers.

Abstract Background Severe hypokalemia is known to cause muscle paralysis, and renal tubular acidosis is a recognized cause. Cystic disease of the kidney is associated with severe hypokalemia. Case presentation We report a 33-year-old male patient who presented with generalized limb weakness caused by severe hypokalemia due to renal tubular acidosis, who was found to have renal medullary cysts. Conclusion The association of cystic renal disease with hypokalemia, and the possible pathophysiological basis of the development of renal cysts in patients with severe hypokalemia, are discussed.

Abstract 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 Background The burden of post-malaria cognitive impairment is often overlooked. Given the large number of infections occurring worldwide, the magnitude of the problem is likely to be substantial. The objectives of this paper are; (i) to assess the evidence on post malarial cognitive impairment or impact on school education; (ii) to assess the possible positive impact of malaria drug prophylaxis on cognition; and (iii) to suggest recommendations on minimizing the burden of post-malarial cognitive impairment Methods PUBMED and SCOPUS were searched for all articles with the key word 'Malaria' in the title field and 'cognitive impairment' in any field. Google Scholar was searched for the same keywords anywhere in the article. The search was restricted to articles published in English within the last 15 years (1995-2010). After filtering of abstracts from the initial search, 44 papers had research evidence on this topic. Results & Discussion Cognitive abilities and school performance were shown to be impaired in sub-groups of patients (with either cerebral malaria or uncomplicated malaria) when compared with healthy controls. Studies comparing cognitive functions before and after treatment for acute malarial illness continued to show significantly impaired school performance and cognitive abilities even after recovery. Malaria prophylaxis was shown to improve cognitive function and school performance in clinical trials when compared to placebo groups. The implications of these findings are discussed.

Abstract Background Several epidemiological studies have shown that cannabis; the most widely used illegal drug in the world, is associated with schizophrenia spectrum disorders (SSD). Aims To assess the characteristics of cannabis use and its association with SSD in a cohort of psychiatrically ill patients and discuss the implications for policy development Methods This is a retrospective analytical study of a cohort of psychiatric patients who received treatment in the psychiatry unit of the Provincial General Hospital, Ratnapura, Sri Lanka over five years (2000 - 2004). The schizophrenia spectrum disorders defined in this article include schizophrenia and the schizoaffective disorders. Results A total of 3644 patient records were analyzed. The percentage of self reported life time cannabis (LTC) use was 2.83% (103, all males). Sixteen percent (576) of the total cohort was diagnosed with SSD by 2009. Male sex and LTC use were significantly associated with SSD (p < 0.01 and 0.001 respectively). In the majority (91.5%), cannabis use preceded the diagnosis. There were 17(16.5%) patients diagnosed as cannabis induced psychosis and 7 (41.2%) of them were subsequently diagnosed as SSD. This group was significantly more likely to have had a past psychiatric consultation, but other demographic and clinical correlates did not differ from the rest of the LTC users. Conclusions Self reported LTC use was strongly associated with being diagnosed with SSD. However we could not identify a particular subgroup of users that are at increased risk to recommend targeted primary prophylaxis. The policy implications of this observation are discussed.

Abstract 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 Background Sri Lanka recorded an extraordinary high suicide rate for adolescents aged 15 - 19 in the early 1990s (46.5/100,000). With this in perspective, the Ministry of Health in Sri Lanka recommends school programmes for adolescents by mental health units of local hospitals. Methods We conducted cross sectional surveys to screen for symptoms of anxiety and depression among students aged 14 - 18 during school mental health programmes. Two schools were randomly selected within the Ratnapura municipality (urban population of approx. 50,000), Sri Lanka and all students aged 14-18 were assessed with self administered (pre tested, Sinhalese translations) questionnaires [Center for epidemiologic studies depression scale, Anxiety screening test of suicide and mental health association international]. Results A total of 445 students were assessed (male-54.4%, female 45.6%). Thirty six percent screened positive for depression (mild depression-17%, severe depression-19%) and 28% screened positive for severe anxiety. Females screened positive for depression and anxiety significantly more than the males (p = 0.0001, 0.005 respectively). Students in classes facing barrier examinations at the end of the year had the highest positivity rates. Examination related issues (36%) were the most commonly cited problem. Recommendations It is recommended that: 1. School mental health development programmes in Sri Lanka concentrate more on reducing examination related stress, and in particular focus on the female students 2. Policy decisions are made to reduce competition for higher education 3. A nationally coordinated survey on mental health of adolescent students is carried out utilizing the island-wide network of medical officers of mental health.