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Background: Leptospirosis is most often diagnosed clinically, and a laboratory test with high diagnostic accuracy is required. Methods: 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). Results: 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. Conclusion: 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.

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

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.

© 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license 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.

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

Primaquine was the only licenced antimalarial hypnozoiticidal drug available until recently. Now there is a newly approved alternative: tafenoquine. This review explores the efficacy of tafenoquine as a primary and terminal prophylactic agent in malaria. Multiple databases (Cochrane Central Register of Controlled Trials [CENTRAL], MEDLINE [PubMed], Embase [Ovid], Scopus, CINAHL [EBSCOhost] and LILACS) were searched for clinical randomised controlled trials that had used tafenoquine for prophylaxis without language or time restrictions. The last date of searching was 13 August 2018. For primary prophylaxis, tafenoquine reduced episodes of malaria compared with placebo, at a dose range from 50 mg weekly to 400 mg monthly in three trials conducted in Ghana, Kenya and Thailand. Two trials compared tafenoquine vs mefloquine, but malaria episodes were too few to reach a conclusion. For terminal prophylaxis, evidence from two trials suggest that tafenoquine may have equal or better efficacy compared with primaquine. All trials excluded pregnant participants or those with G6PD deficiency. Tafenoquine is effective for both primary and terminal prophylaxis. If used for primary prophylaxis it may continue to offer protection against vivax relapses after exposure has ended (as terminal prophylaxis).

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

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

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., Plain language summary Tafenoquine for preventing relapse in people with vivax malaria What was the aim of this review? The aim of this review was to see if tafenoquine could prevent relapses of vivax infections and if this effect is equivalent to that of standard‐dose primaquine. Standard‐dose primaquine is defined as 15 mg/day for 14 days for adults. Key messages Tafenoquine prevents vivax malaria relapses (measured as recurrences of infection in all studies as it is not possible to differentiate a true relapse from a reinfection) in adults compared to no relapse prevention treatment (placebo). There is also probably little or no difference between tafenoquine and primaquine in preventing relapses. The evidence was of moderate certainty due to the low number of studies and few data. There is probably little or no difference in the overall adverse events with tafenoquine compared to placebo or primaquine. However, we are uncertain if tafenoquine causes more serious adverse events such as a drop in blood haemoglobin. What was studied in this review? Vivax malaria is caused by the parasite Plasmodium vivax. The disease includes a dormant (inactive) stage of liver infection and this can cause relapse (worsening) unless it is treated. The most frequently used medicine for relapse prevention until recently was primaquine, but now there is a new alternative named tafenoquine. The US agency responsible for protecting public health, the Food and Drug Administration (FDA), recommends tafenoquine for relapse prevention at a single 300 mg dose. Compared to primaquine, which is usually given daily for 14 days, single‐day dosing provides a significant advantage. However, both primaquine and tafenoquine can cause rupture or destruction of red blood cells (called haemolysis) in people with a hereditary condition called glucose‐6‐phosphate dehydrogenase (G6PD) enzyme deficiency. We conducted a Cochrane Review on the effect of tafenoquine on clearing the dormant P vivax parasites in infected people to prevent a relapse. However, it is difficult to differentiate between a true relapse and a new infection in the same individual unless the person was removed from a malaria‐endemic area after initial treatment. All trials included in this review did not do that and have actually measured recurrences as a proxy measure to infer on relapses. While acknowledging this limitation, in giving recommendations and results in this review we used the word 'relapse' as preventing relapses is the intention for using tafenoquine as a single dose in these trials. What are the main results of the review? We examined the research published up to 3 June 2020. We identified three trials conducted in nine countries in 747 adults with confirmed P vivax malaria. All adults received chloroquine (to clear the parasites from the blood) and some groups received either tafenoquine in a single dose of 300 mg, primaquine or placebo (an inactive tablet matched for the duration of primaquine). All were observed for recurrences of P vivax malaria (up to six months) and all trials tested people for G6PD activity and excluded people who were deficient. Pregnant women and children were also excluded. Adults receiving tafenoquine 300 mg had fewer relapses (inferred from the lower number of recurrences of infection) than adults who had placebo (moderate‐certainty evidence). There was probably little or no difference between Tafenoquine 300 mg and primaquine for relapse prevention (moderate‐certainty evidence). There is probably little or no difference in overall side effects between tafenoquine and primaquine (moderate‐certainty evidence). We are uncertain though if tafenoquine causes more serious adverse events compared to placebo or premaquine (for example, haemolysis; very low‐certainty evidence).

Background Repurposing hydroxychloroquine (HCQ) and chloroquine (CQ) as antiviral agents is a re-emerging topic with the advent of new viral epidemics. Aims To summarize evidence from human clinical studies for using HCQ or CQ as antiviral agents for any viral infection. Sources PubMed, EMBASE, Scopus, Web of Science for published studies without time or language restrictions; Cochrane Clinical Trial Registry and Chinese Clinical Trials Registry for trials registered after 2015; MedRxiv for preprints within the last 12 months. Content Study eligibility criteria were interventional and prospective observational studies (with or without a control group). Participants were adults and children with a confirmed viral infection. Interventions included the use of CQ or HCQ as antiviral agent in one or more groups of the study. Two authors independently screened abstracts, and all authors agreed on eligible studies. A meta-analysis was planned if studies were available which were similar in terms of participants, intervention, comparator and outcomes. Nineteen studies (including two preprints) were eligible (HIV 8, HCV 2, dengue 2, chikungunya 1, COVID-19 6). Nine and ten studies assessed CQ and HCQ respectively. Benefits of either drug for viral load suppression in HIV are inconsistent. CQ is ineffective in curing dengue (high-certainty evidence) and may have little or no benefit in curing chikungunya (low-certainty evidence). The evidence for COVID-19 infection is rapidly evolving but at this stage we are unsure whether either CQ or HCQ has any benefit in clearing viraemia (very-low-certainty evidence). Implications Using HCQ or CQ for HIV/HCV infections is now clinically irrelevant as other effective antivirals are available for viral load suppression (HIV) and cure (HCV). There is no benefit of CQ in dengue, and the same conclusion is likely for chikungunya. More evidence is needed to confirm whether either HCQ or CQ is beneficial in COVID-19 infection.

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

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

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

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

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

Background Blood smear changes have never been investigated as a potential tool to aid in the diagnosis of leptospirosis. Methods Blood smears prepared from patients with leptospirosis, dengue and sepsis within the first 5 days of illness were reported by haematologists blinded to the diagnosis. Results A total of 20, 28 and 22 patients with leptospirosis, dengue and sepsis, respectively, were analysed. Neutrophil leucocytosis, toxic changes in neutrophils, left shift, reactive lymphocytes, target cells and thrombocytopaenia were seen in 60%, 70%, 40%, 70%, 50% and 65% of the leptospirosis patients, respectively. The combination of reactive lymphocytes with toxic neutrophils or neutrophil leucocytosis was highly suggestive of leptospirosis. Conclusions Peripheral blood smear findings may be helpful in differentiating leptospirosis from other common acute febrile illnesses.

Context Coagulation abnormalities have been observed among leptospirosis patients. However, coagulopathy in severe leptospirosis has not been further characterized. Aims The aim of this study was to evaluate conventional coagulation and rotational thromboelastometry (ROTEM®) parameters in leptospirosis patients. Settings and design This prospective cross-sectional comparative study included patients presenting to a tertiary hospital in Sri Lanka with clinically and serologically confirmed leptospirosis (14 severe and 6 mild), dengue (6), sepsis (5), and 6 healthy individuals. Subjects and methods Blood samples were collected between the 3rd and 10th days of illness for prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), fibrinogen, lupus anticoagulant, factors VII and VIII, D-dimer, platelet count, and ROTEM. Statistical analysis used ANOVA post hoc comparison using Bonferroni was applied to compare groups. Results PT and aPTT were prolonged in leptospirosis patients and were corrected with normal plasma. TT was not significantly prolonged in leptospirosis. Fibrinogen was significantly elevated in severe leptospirosis (P = 0.001) and sepsis (P = 0.001) compared with healthy controls and dengue. Thirty percent of leptospirosis patients had thrombocytopenia (17% in mild and 36% in severe). No significant differences were seen in inTEM clotting time (CT) and exTEM CT in leptospirosis when compared to the other three groups. inTEM clot formation time (CFT) and exTEM CFT in dengue were significantly higher compared to severe (P = 0.001) and mild (P = 0.005) leptospirosis. inTEM maximum clot firmness (MCF) (P = 0.001) and exTEM MCF (P = 0.001) were significantly lower in dengue than in leptospirosis. Only one patient with leptospirosis had bleeding manifestations. Conclusions Abnormalities in conventional coagulation parameters occur in leptospirosis. However, ROTEM parameters in leptospirosis are not significantly altered.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: 1. To assess the effectiveness of primaquine and tafenoquine for primary prophylaxis againstPlasmodium vivax andPlasmodium falciparum infections. 2. To assess the effectiveness of tafenoquine for terminal prophylaxis of vivax malaria. 3. To compare the safety profile and compliance rates of tafenoquine and primaquine when used for primary (P. vivax and P. falciparum infections) and terminal (P. vivax infections) prophylaxis.

COVID-19 has caused a devastating pandemic, infecting 3,090,445 people and causing 217,769 deaths, as of 30 April, 2020. The current evidence base for selected drugs repositioned to treat COVID- 19 are summarized here. Chloroquine (CQ) and hydroxychloroquine (HCQ) block the entry of the SARS-CoV-2 virus into cells and have immunomodulatory effects. Early, poor quality studies pointed to benefit with CQ and HCQ treatment in COVID-19 infection, but no further evidence supporting their use is available to date, and the drugs cannot be recommended for treatment or prophylaxis. However, several countries use CQ or HCQ for compassionate treatment. Lopinavir-ritonavir, which is effective against HIV, was evaluated in one clinical trial which showed no benefit. Remdesivir, a drug developed for EBOLA, has been shown to have in-vitro efficacy against SARS-CoV-2, and the treatment has been used on compassionate grounds in severe cases. Limited studies have shown clinical improvement with remdesivir which is approved for emergency use in severe COVID-19. The RNA polymerase inhibitor favipiravir has been shown to improve clinical features, hasten viral clearance, and improve HRCT findings. Corticosteroids have shown no benefit. Trials are underway with the IL-6 receptor blocking monoclonal antibody tocilizumab, with retrospective data showing reduction in inflammatory markers and clinical improvement. Convalescent plasma has been shown to be of some benefit in severe cases of SARS, MERS and H1N1 influenza, and is recommended by the FDA for those with serious or immediately life-threatening infection with COVID-19. Several large randomized controlled trials are underway, evaluating these repositioned therapies as well as many other treatments. No effective specific treatments are available for COVID- 19 infection as yet.

IMPORTANCE: Poorly controlled hypertension is a leading global public health problem requiring new treatment strategies. OBJECTIVE: To assess whether a low-dose triple combination antihypertensive medication would achieve better blood pressure (BP) control vs usual care. DESIGN, SETTING, AND PARTICIPANTS: Randomized, open-label trial of a low-dose triple BP therapy vs usual care for adults with hypertension (systolic BP >140 mm Hg and/or diastolic BP >90 mm Hg; or in patients with diabetes or chronic kidney disease: >130 mm Hg and/or >80 mm Hg) requiring initiation (untreated patients) or escalation (patients receiving monotherapy) of antihypertensive therapy. Patients were enrolled from 11 urban hospital clinics in Sri Lanka from February 2016 to May 2017; follow-up ended in October 2017. INTERVENTIONS: A once-daily fixed-dose triple combination pill (20 mg of telmisartan, 2.5 mg of amlodipine, and 12.5 mg of chlorthalidone) therapy (n = 349) or usual care (n = 351). MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion achieving target systolic/diastolic BP (

The aim of this study was to assess the inflammatory cytokine response and possible association with antimicrobial treatment with penicillin, ceftriaxone, and doxycycline in acute leptospirosis. In the early acute stage, interleukin-10 (IL-10) levels were higher in mild cases than in severe cases ( P = 0.01). IL-6 and IL-8 levels were low in patients who received >5 antimicrobial doses ( P < 0.01). IL-8 levels were negatively correlated with the number of ceftriaxone doses administered ( r = −0.315; P = 0.031). Further studies are needed to evaluate the possible downregulation of proinflammatory cytokines by ceftriaxone in leptospirosis.

Breast cancer is a global health concern and is a major cause of death among women. In Oman, it is the most common cancer in women, with an incidence rate of 15.6 per 100,000 Omani females. Various anticancer remedies have been discovered from natural products in the past and the search is continuing for additional examples. Cytotoxic natural compounds may have a major role in cancer therapy either in potentiating the effect of chemotherapy or reducing its harmful effects. Recently, a few studies have reported advantages of using crude camel milk in treating some forms of cancer. However, no adequate data are available on the lyophilised camel's milk responsibility for triggering apoptosis and oxidative stress associated with human breast cancer. The present study aimed to address the role of the lyophilised camel's milk in inducing proliferation repression of BT-474 and HEp-2 cells compared with the non-cancer HCC1937 BL cell line. Lyophilized camel's milk fundamentally repressed BT-474 cells growth and proliferation through the initiation of either the intrinsic and extrinsic apoptotic pathways as indicated by both caspase-3 mRNA and its action level, and induction of death receptors in BT-474 but not the HEp-2 cell line. In addition, lyophilised camel's milk enhanced the expression of oxidative stress markers, heme-oxygenase-1 and reactive oxygen species production in BT-474 cells. Increase in caspase-3 mRNA levels by the lyophilised camel's milk was completely prevented by the actinomycin D, a transcriptional inhibitor. This suggests that lyophilized camel's milk increased newly synthesized RNA. Interestingly,it significantly (p

INTRODUCTION Sri Lanka has eliminated local transmission of malaria. Assessing physician preparedness for early case detection is important, in order to prevent re-establishment of local transmission. METHODS Adherence to malaria screening practices in patients admitted with fever to 12 hospitals in a previously malaria endemic district was evaluated using a cross sectional survey. In addition, knowledge and attitudes among doctors on current malaria surveillance practices and treatment recommendations was assessed. RESULTS Of 403 fever patients, 150 warranted screening for malaria under the criteria defined by the Anti Malaria Campaign (AMC), with 93 of them having fever for over 7 days. Of these eligible patients, 12.6% (19/150) were investigated by doctors (including 3 persons with fever over 7 days), 14.6% (22/150) by laboratory staff and 72.6% (109/150) by the research team. The majority of doctors were not familiar with the treatment guidelines for malaria (76.5%, 75/98). CONCLUSIONS Mandatory continuous medical education programmes need to continue to ensure that malaria remains on the differential diagnosis of a fever patient, especially in patients with fever over 7 days. It is essential to publicize the availability of free-of-charge malaria diagnostic facilities, and to ensure that proper notification procedures are followed when a malaria patient is diagnosed.

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.

Introduction: Dengue is endemic in the tropics, and complications involving organ systems are seen with varying incidence. Methodology: We performed a systematic review. MEDLINE, EMBASE, Scopus SciVerse, Google Scholar, and LILACS were searched for papers providing information on cardiac involvement in dengue. Results: Cardiac involvement is not uncommon in dengue infection and is often transient, but may be associated with significant morbidity and even mortality. Direct viral invasion, immune mechanisms, electrolyte imbalance, derangement of intracellular calcium ion storage, lactic acidosis, and ischemia due to hypotension all play a role in myocardial dysfunction. The manifestations of cardiac involvement include clinical, electrocardiographic, echocardiographic, cardiac enzyme, and histopathologic abnormalities. Echocardiography appears to be a useful tool for detecting myocardial involvement and should be performed in patients with electrocardiographic abnormalities or hemodynamic instability. Treatment is largely supportive, though there are some anecdotal reports of improvements with specific agents. Conclusions: Knowledge on cardiac manifestations in dengue is limited, and further studies are needed to establish the exact pathophysiology and role of specific agents in the prevention and treatment of cardiac complications in dengue.

Objective The objectives of this study were to; (a) evaluate the current practices of peer assisted learning among second year and final year medical students of Faculty of Medicine, University of Colombo, Sri Lanka; (b) identify reasons for engaging in peer assisted learning; (c) identify perceived weaknesses in current learning activities; and (d) determine student characteristics associated with engaging in peer assisted learning. Results This cross sectional study interviewed two hundred and eighty-four eligible students. Average number of hours spent on peer assisted learning during a week was significantly greater among second year students compared to final year students (15.1 vs. 7.1 h, p

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

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

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

Background Only a limited number of multiple synchronous primary malignancies of the pancreas have been reported in the medical literature. We report a case of two solid malignant tumors of the pancreas diagnosed preoperatively. Case presentation We describe a 65-year-old Sri Lankan woman who presented with progressive obstructive jaundice. Initial contrast-enhanced computed tomography imaging detected a malignant tumor at the tail of her pancreas. A second tumor of the pancreatic head was detected with integrated imaging using multidetector computed tomography and multimodal magnetic resonance imaging. She underwent total pancreaticoduodenectomy and splenectomy. Gross examination of the specimen confirmed the presence of two separate tumors. Histology of the ampullary tumor showed pancreatic-type adenocarcinoma and the tumor in the tail of her pancreas showed a colloid-type adenocarcinoma. Conclusion The possibility of multiple primary malignant solid tumors of different types with malignant potential has to be considered even without background pathology when managing multiple tumors in the pancreas.

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

Introduction: Dengue hemorrhagic fever (DHF) is a major cause of morbidity and mortality in tropical regions. Serum free calcium (Ca2+) is known to be important in cardiac and circulatory function. We evaluated association between serum Ca2+ level and severity of dengue. Methodology:A cross-sectional study was carried out at a tertiary care private hospital in Sri Lanka. A probable case of dengue was diagnosed and classified according to World Health Organization criteria and confirmed by either IgM antibody, PCR, or NS1 antigen detection. Socio-demographic details were collected using an interviewer-administered questionnaire. Results: The sample size was 135. The mean age was 26.1 years, and the majority were males (n = 80, 59.3%). DHF was diagnosed in 71 patients (52.6%). Mean serum Ca2+ level of the study population was 1.05 mmol/L (range 0.77–1.24). Mean serum Ca2+ was significantly higher in patients with dengue fever (DF) (1.09 mmol/L) than in those with DHF (1.02 mmol/L) (p < 0.05). A significant difference was observed between mean serum calcium levels of DHF I and DHF II. Prevalence of hypocalcemia in DHF and DF patients was 86.9% (n = 60) and 29.7% (n = 11), respectively (p < 0.05). Conclusions: Serum Ca2+ levels significantly correlated with dengue severity. Serum Ca2+ levels were significantly lower and hypocalcemia was more prevalent in patients with DHF than in patients with DF. Further studies are required to determine whether hypocalcemia can be utilized as a prognostic indicator and to evaluate effectiveness of calcium therapy in prevention of dengue complications.

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 (FEV 1 ) measured at 90 min after adjustment for baseline FEV 1 (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.

Introduction Sri Lanka has a predominantly rural population. However, there is a dearth of research on health and socioeconomic issues in this group. Objective To describe basic socioeconomic characteristics and health profile in a rural population. Methods A descriptive cross-sectional household survey was conducted in 1950 households in three rural districts, selected by a three-stage stratified cluster sampling method. Results The population pyramid showed an ageing population (dependency ratio of 50%). Only 39% had completed GCE (ordinary level). Unemployment rates were high (25% males, 76% females). Agriculture and related work were main occupations. Most lacked amenities (e.g. 61% households lacked a refrigerator) and practiced inappropriate methods of waste disposal (e.g. open burning by 72%). Household illnesses were frequent: episodes of acute illness within two weeks, injuries within past year and chronic illness were reported from 35.9%, 14.9% and 48.3% households. The prevalence of chronic diseases in adults > 20 years were high: diabetes 13.5%, hypertension 16.7% and overweight/obesity 28.2%. Of the males, 22.1% smoked and 12.3% took alcohol. Almost 25% adults chewed betel. Reports of snake bite, dog bites and suicide/attempted suicide were seen in 15.5%, 9.7% and 3.0% households respectively. Conclusions This study shows a unique clustering of health-related problems in rural Sri Lanka. This was characterized by demographic transition, burden from snake bites, chronic diseases and acute illnesses. There were resource limitations and low levels of education. Cohort studies and comparisons with urban areas will enable further elucidation of determinants of health and other issues in rural Sri Lanka.

Chronic kidney disease of unknown etiology (CKDu) is a major healthcare issue in Sri Lanka. This study included 125 consecutive patients with a diagnosis of CKDu undergoing renal biopsy at one hospital from 2008 to 2012. Associations between renal outcome parameters, epidemiological data, and histopathological findings were examined and regression models constructed based on univariate associations with outcome variables as serum creatinine >1.2 and stage of CKD >3. The mean patient age was 46.21 years (standard deviation = 11.64). A marked male predominance was noted. A positive family history of CKD was seen in 35.8%. Prominent histopathological features were glomerular sclerosis (94.8%), interstitial infiltration (76%) with lymphocytic infiltration, interstitial fibrosis (71.2%), and tubular atrophy (70.4%). Importantly, significant histological changes were seen in patients with early CKDu. For CKD stage >3 independent associations were: interstitial fibrosis [P = 0.005; odds ratio (OR) =0.153] and interstitial infiltrate (P = 0.030; OR = 0.2440. For serum creatinine >1.2, independent predictors were >50% glomerular sclerosis (P = 0.041; OR = 0.92), tubular atrophy (P = 0.034; OR = 0.171, and more than 40 residential life years (P = 0.009; OR = 9.229). Chronic tubulointerstitial nephritis (TIN) appears to be the predominant histopathological finding in patients with CKDu, with significant renal pathology established early on in the course of the disease. Interstitial infiltration appears to be an independent association of advancing CKD, CKDu, histopathology, histology, and TIN.

Uncontrolled studies suggest that magnesium sulphate controls spasms in patients with established tetanus. We performed a meta-analysis of controlled trials that compared magnesium sulphate with placebo or diazepam for the treatment of patients with tetanus. We searched PubMed, Scopus, Embase and the Cochrane clinical trials registry. Three studies met the inclusion criteria, containing 275 participants (199 male patients, 72.4%). Magnesium sulphate did not reduce mortality, relative risk (95% CI): vs placebo, 0.80 (0.41-1.58); vs diazepam, 1.11 (0.70-1.75). The data on duration of total intensive care unit stay, total hospital stay and the need for ventilatory support were conflicting and pooling of results could not be done due to methodological differences of individual trials. More controlled trials are needed to assess the effect of magnesium sulphate on reducing autonomic instability, spasms, duration of intensive care and hospital stays and the need for mechanical ventilation.

Leptospirosis is a neglected global disease with significant morbidity and mortality. Cardiac complications such as chest pain, arrhythmias, pulmonary oedema and refractory shock have been reported in patients with severe disease. However, the frequency and extent of cardiac involvement in leptospirosis, are under-reported and poorly understood. Multiple factors may contribute to clinical manifestations that suggest cardiac involvement, causing diagnostic confusion. A variety of electrocardiographic changes occur in leptospirosis, with atrial fibrillation, atrioventricular conduction blocks and non-specific ventricular repolarization abnormalities being the most common. Electrolyte abnormalities are likely to contribute to electrocardiographic changes; direct effects on Na(+)-K(+)-Cl(-) transporters in the renal tubules have been postulated. Echocardiographic evidence of myocardial dysfunction has not been adequately demonstrated. The diagnostic value of cardiac biomarkers is unknown. Histopathological changes in the myocardium have been clearly shown, with myocardial inflammation and vasculitis present in postmortem studies. Nonetheless, the pathophysiology of cardiac involvement in leptospirosis is poorly understood. Cardiac involvement, demonstrated electrocardiographically or clinically, tends to predict poor outcome. No specific therapies are available to prevent or treat cardiac involvement in leptospirosis; current management is based on correction of deranged homeostasis and supportive therapy. Evidence suggests that direct myocardial damage occurs in patients with severe leptospirosis, and further studies are recommended to elucidate its pathophysiology, clinical features and contribution to overall prognosis, and to identify appropriate diagnostic investigations and specific therapies.

Objective To determine whether blood nitrite levels are elevated in patients with leptospirosis. Methods Male patients fulfilling clinical and epidemiological criteria for a diagnosis of leptospirosis were recruited. Those with MAT titre of ≤400 together with those seroconverting to a titer of ≤200 were included in the analysis. Serum nitrite levels were measured in these patients and age, sex matched healthy controls. Results Patients from 3 hospitals ( n =75) were screened during a 3 month period from 28th June to 3rd September 2009, of whom 20 were eligible for the study. Serum nitrite levels were found to be significantly higher in patients with acute leptospirosis [ n =20, (0.359±0.229)μ M] compared to controls [( n =13,(0.216±0.051)μ M]( P =0.014). A significant correlation was also observed between the MAT titre and the day of illness ( r = 0.547; P Conclusions Serum nitrite levels are higher in patients with acute leptospirosis compared to age and sex matched controls. No correlation could be assessed with severity of illness, as sample size was inadequate to determine this.

This review concentrates on different aspects of malaria chemoprophylaxis, namely drug combinations, resistance, impact of malaria prevention in pregnancy and cost effectiveness. A MEDLINE search was performed for all articles with the key word ‘Malaria’ in the title field and ‘Prophylaxis’ in any field. The search was restricted to articles published in English within the last decade (1999–2009). Data sources included review articles published in core clinical journals, cohort studies, interventional studies, case control studies and cross sectional analyses. The mechanism of action, trial evidence of efficacy, side effects and geographical distribution of resistance is discussed for each prophylactic drug regimen. Impact of prophylaxis in pregnancy and the cost considerations are discussed under two separate sub topics.

Objective: This study was designed to compare diagnosis of trichomoniasis by culture, wet smear examination, and Giemsa stain. A modified technique was used to transport and prepare the specimen to ensure parasite viability prior to Giemsa staining. Materials and Methods: A clinic-based prospective study was carried out in association with the National STD/AIDS Control Programme over a period of 18 months. Three swabs were collected from the posterior fornix of 346 newly registered female patients for diagnosis of trichomoniasis. A wet smear was prepared using the first swab. The second swab was placed in 5 mL of 0.9% saline with three drops of 5% glucose at room temperature and centrifuged twice at a low speed prior to preparation of a Giemsa stained smear. The third swab was for culture. The three tests were performed independently. The specificity and sensitivity of the wet smear and Giemsa stain were compared to culture. Results: With culture, the prevalence of trichomoniasis was 6.9% (95% CI: 4.1-9.3%). The Giemsa-stained smear was found to be highly sensitive (100%, 95% CI: 86.2-100%) and specific (99.69%, 95% CI: 98.26-99.95%) compared to culture. The wet smear was less sensitive (95.83%, 95% CI: 79.76-99.26%) but equally specific (100%, 95% CI: 98.82-100%). Conclusion: In developing countries, facilities for using culture are limited and wet smear examination in the field is also difficult due to the immediate need for laboratory facilities. Our study demonstrated that, in this setting, using a transport medium prior to Giemsa staining is a feasible alternative, with a high-diagnostic yield.

Many trials have explored the efficacy of individual drugs and drug combinations to treat bancroftian filariasis. This narrative review summarizes the current evidence for drug management of bancroftian filariasis. Diethylcarbamazine (DEC) remains the prime antifilarial agent with a well-established microfilaricidal and some macrofilaricidal effects. Ivermectin (IVM) is highly microfilaricidal but minimally macrofilaricidal. The role of albendazole (ALB) in treatment regimens is not well established though the drug has a microfilaricidal effect. The combination of DEC+ALB has a better long-term impact than IVM+ALB. Recent trials have shown that doxycycline therapy againstWolbachia, an endosymbiotic bacterium of the parasite, is capable of reducing microfilaria rates and adult worm activity. Followup studies on mass drug administration (MDA) are yet to show a complete interruption of transmission, though the infection rates are reduced to a very low level.

Background: The Faculty of Medicine, University of Colombo, has an integrated curriculum in which teaching of public health takes place through a series of modules which span the full five-year study programme. Aim: To assess final year medical student perceptions regarding the public health curriculum and to identify factors which influence this. Materials and Methods: The study was cross sectional. Convenience sampling was utilized on final-year students of the Faculty of Medicine, University of Colombo, Sri Lanka. A self-administered 4-point Likert scale questionnaire covered general opinion on public healthcare and perceptions about the curriculum. Data were analyzed using descriptive statistics and Chi-square tests. Results: One hundred and eighty four students (94%) participated in the study. Eighty-two percent (148) viewed public health as an important field. Only 9% (16) were interested in a career in public health. A significant association was found between choosing public health as career and the following: perception of public health as an important field; holding a good opinion about public health prior to commencement of the course; having found the field-based experience enjoyable and beneficial to the community; and feeling competent to work in the community at the end of the course (P < 0.01). With regard to teaching methods, group activities and discussion-centered activities were identified positively (153, 83% and 125, 68% respectively). The majority of students indicated that they were not stimulated to read more on the subject or regularly revise what they have learnt, both during the introductory public health programme and during the final year. Conclusions: The curriculum has been able to create a positive opinion about public health. However, students lack enthusiasm to learn independently. Experiential, group-centered teaching activities and a constructivist approach may be more effective in promoting independent learning. Perceptions are important and should aid in structuring the curricula.

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.

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.

This retrospective analytical study aimed at establishing a database of patients who underwent renal transplant under the Faculty of Medicine (Colombo) renal transplant programme. Patients who underwent renal transplant under the programme from 31st December 2004 to 31st December 2006 were included in the study. The objective was to build a profile of renal transplant patient with focus on post KT infections and complications of renal transplants. An interviewer administered questionnaire was used. N=72, government sector 46 (62.5 %) and private sector 26 (37.5 %). Eighteen (25%) had died by February 2007. Forty three patients (58.3%) were interviewed and twelve patients could not be contacted. Of the interviewed, 28 (38.9%) were on azathioprine, prednisolone and cyclosporin while 15 (20.8%) were on prednisolone, cyclosporin and mycophenolate mofetil. Four patients had symptomatic cytomegalovirus infection and 5 had tuberculosis post transplant. Of all infections, the most commonly reported was urinary tract infection (11 cases). Out of the total sample, 33 (45.8 %) had received induction therapy with either basiliximab (8) or daclizumab (25). There was no significant benefit in protection against acute rejection in those who took induction therapy. Acute rejection was the most commonly encountered complication with 9 cases (12.5 %) being reported over the study period. Of late complications, most were due to immunosuppression. Overall 2 year survival was 75%, with no significant difference depending on the center of transplant.

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.

Dengue infection causes significant morbidity and mortality worldwide. Therapeutic options for severe thrombocytopaenia and shock syndrome, the main causes of mortality, are limited. Careful fluid management is the mainstay of treatment. The immunological basis of the life-threatening manifestations of severe dengue together with the potentially beneficial immunomodulatory effects of intravenous immunoglobulins (IVIG) suggest a possible place for treatment with this expensive therapy. Trials so far have not shown significant benefit in terms of survival or improvement in clinical parameters with IVIG. However, evidence is very limited, and there is clearly a place for well-designed randomized controlled trials investigating the beneficial effects of IVIG in the various life-threatening manifestations of dengue.

12.00 Normal 0 false false false EN-US X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;} The safety of critically ill patients in intensive care units is an important aspect of medical care. Many human factors contribute to deficiencies and errors in patient care in the intensive care setting, such as long working hours, high levels of stress, lack of enough people, may cause human errors and affecting the effectiveness of the decisions of the physician. Several attempts have been made to increase the effectiveness of such decisions by issuing early alerts on adverse patient conditions. However, such alerts are based on single parameter variations, and not on the relationship between multiple parameter variations. We developed a computer-based model is an integrated solution which identifies adverse patient events based on multiple parameter variations, and then provides predictive treatment suggestions based on the likely clinical conditions which result in the parameter variations. The proposed system follows an interactive communication cycle in order to properly notify the responsible treating physicians at different tiers of responsibility. Our model is capable of early identification of adverse conditions and providing suitable treatment suggestions, thus acting as a decision support system to assist the treating physician. DOI: 10.4038/sljcc.v1i1.942