Conference Papers
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This collection contains abstracts of conference papers, presented at local and international conferences by the staff of the Faculty of Medicine
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Item Oxidative stress and antioxidant deficiency in the β-thalassaemia in Sri Lanka(Sri Lanka Medical Association, 2021) Perera, S.; Allen, A.; Mettananda, S.; Rodrigo, R.; Perera, L.; Darshana, T.; Moggach, F.; Jackson-Crawford, A.; Heirene, L.; Fisher, C.; Olivieri, N.; Rees, D.; Allen, S.; Premawardhena, A.Introduction In the β thalassaemias oxidative stress is potentially high and this could be further exacerbated in the absence of robust antioxidant defences, such as nutritional vitamin C and E deficiencies. We undertook a comprehensive assessment of oxidant, antioxidant and inflammatory status in patients with subtypes of β-thalassaemia to study these factors in detail. Methods Consenting patients attending the thalassaemia centre in Ragama, (between November 2017 and June 2018) were assessed for the following: methaemoglobin, plasma haemoglobin, heme and ferritin as sources of oxidants, plasma haptoglobin, hemopexin and vitamins C and E as markers of antioxidants, plasma interleukin-6 and C-reactive protein for inflammation. Fruit and vegetable intake was determined by dietary recall. Results 162 patients were recruited. (59 HbE β-thalassaemia, 50 β-thalassaemia major, 40 β-thalassaemia intermedia, 13 HbS β-thalassaemia. Median age was 26.0 years (IQR 15.3-38.8), 101 (62.3%) were female. Oxidants were frequently increased and antioxidants depleted with high levels of oxidant damage, hypoxia and inflammation. Abnormalities were most severe in HbE-β thalassaemia and least severe in β thalassaemia intermedia. Oxidative stress was also more severe in splenectomised patients. Plasma vitamin C concentration was below the lower level of quantitation in 86/160 (53.8%) patients and vitamin E in 130/160 (81.3%) patients. Less than 15% of patients ate fresh fruits or raw vegetables frequently. Conclusion Markedly increased oxidative stress and antioxidant deficiency were observed in this study group, especially in those with HbE β-thalassaemia. Vitamin C & E supplementation may have a role in the long-term management of thalassaemia syndromes.Item Efficacy and Safety of Oral Hydroxyurea in Patients with Transfusion Dependent β Thalassaemia: a Randomized Double-Blind Placebo-Controlled Clinical Trial(Sri Lanka Medical Association, 2020) Yasara, N.; Wickramarathne, N.; Silva, I.; Hameed, N.; Attanayaka, A.M.K.R.; Jayasinghe, V.L.; Wickramasinghe, N.; Rodrigo, R.; Perera, L.; Mettananda, K.C.D.; Manamperi, A.; Premawardhena, A.; Mettananda, S.INTRODUCTION AND OBJECTIVES: Patients with β- thalassaemia require blood transfusions and iron chelation for life. Hydroxyurea is a licenced medication for sickle cell disease but its usefulness in transfusion dependent β-thalassaemia is unclear. Here, we aim to assess the efficacy and safety of oral hydroxyurea in patients with transfusion dependent β-thalassaemia. METHODS: A phase III randomized double-blind placebo-controlled clinical trial was conducted at Thalassaemia Unit of Colombo North Teaching Hospital in 2019. Forty-one patients with transfusion dependent β-thalassaemia were randomized into hydroxyurea (10-20mg/kg/day) or placebo (pharmaceutically inert capsule identical to hydroxyurea) groups. Transfused blood volume, pre-transfusion haemoglobin, haemoglobin F level and side effects were monitored monthly during 6- month treatment and 6-month follow-up periods. Adverse events were assessed by trained medical officers. The study was approved by ethics committee of University of Kelaniya and registered in Sri Lanka Clinical Trials Registry (SLCTR/ 2018/024). RESULTS: Of the 41 (hydroxyurea-20; placebo-21) patients, three discontinued treatment due to thrombocytopenia (hydroxyurea-2) and rash (placebo-1). Baseline characteristics of two groups were similar. Mean pre-transfusion haemoglobin (8.52+0.57 vs 8.38+0.55, p=0.45) and haemoglobin F levels (4.3+7.1% vs 3.1+1.9%, p=0.48) were higher in hydroxyurea group compared to placebo. Also, transfused blood volume was lower in hydroxyurea group (102+24ml/kg vs 111+27ml/kg, p=0.3). However, none were statistically significant. Based on elevation of haemoglobin F (>1.5% from baseline), we identified 6/18 patients as hydroxyurea responders. Hydroxyurea responders required significantly lower blood volume (87+13ml/kg) compared to non-responders (110+25ml/kg, p=0.05) and placebo group (111+27ml/kg, p<0.05) while maintaining higher pre-transfusion haemoglobin level (8.6+0.5 vs 8.4+0.5 and 8.3+0.5). No serious side effects were reported. CONCLUSIONS: One-third of patients with transfusion dependent β-thalassaemia responded to hydroxyurea treatment requiring 20% less blood compared to controls. No serious side effects were reported following hydroxyurea treatment.Item Identifying haemoglobinopathy traits and iron deficiency in Sri Lanka using the dtchlorophenolindophenol (DCIP) and one- tube osmotic fragility (OF) tests and measurement of red cell zinc protoporphyrin (ZPP)(Sri Lanka Medical Association., 2019) Perera, P. S.; Premawardhena, A.; Mettananda, S.; Rodrigo, R.; Perera, L.; Weatherall, D. J.; Allen, S.; Allen, A.INTRODUCTION & OBJECTIVES: Effective, low-cost, point-of-care tests are needed for haemoglobinopathy traits and iron deficiency throughout Southeast Asia. The objective of this study is to evaluate a combination of simple, low cost, easy-to-interpret and rapid tests as a "one-stop" screening procedure for identifying carriers of haemoglobin variants and iron deficiency in Sri Lanka. METHODS: Between November 2017 and May 2018, the KKU-OF and KKU modified DCIP tests (KKU, Thailand) were compared with High Performance Liquid Chromatography (HPLC) in a cross-sectional survey of 1324/1332 (99.4%) children attending secondary schools in Gampaha district, Sri Lanka. Iron deficiency was indicated in children with a raised red cell ZPP (Helena Biosciences), and confirmed by measurement of low serum ferritin and normal C- reactive protein (CRP). RESULTS: Median age was 17 years (IQR 16-18), all were Sinhalese and 814/1324 (61.5%) were female. HPLC identified 26 students with β-thalassaemia trait and 3 with HbE trait. The KKU-OF test correctly identified all 26 students with β-thalassaemia trait (sensitivity=100%) but was also positive in 288 samples with a normal HPLC result (specificity= 1007/1295; 85.5%). The KKU-DCIP test was positive only in the 3 students with HbE (100% sensitive and 100% specific). Iron deficiency was present in 148/1318 (11.2%) students. CONCLUSION: This one-stop approach may be an effective and affordable procedure in screening for haemoglobinopathy traits and identifying iron deficiency. We are investigating the causes of the false positive OF test results and planning large scale studies to assess cost-effectiveness.Item Microcytic anaemia in children: Do we really know the cause?(Sri Lanka Medical Association, 2018) Paranamanna, S.; Fernando, V. R.; Suranjan, P. D. M.; Rodrigo, R.; Perera, L.; Vipulanayake, U. K. T.; Fernando, A. G. L. N. P.; Fernando, A.M.; Costa, Y.; Dayanath, D.K.T.P.; Premawardhena, A.; Mettananda, S.INTRODUCTION & OBJECTIVES: Microcytic anaemia is common among children and is often attributed to iron deficiency. Other causes are given less priority. We aimed to describe the aetiology of microcytic anaemia among children aged between 6-59 months.METHODS: A descriptive study was conducted at Teaching Hospital, Ragama from March 2016 to February 2017. All newly diagnosed patients with microcytic anaemia (haemoglobin <11 g/dL and mean corpuscular volume <80 Fl) were recruited. Data was collected using an interviewer-administered questionnaire and 5ml of venous blood was obtained for full blood count, serum ferritin, capillary electrophoresis and alpha-globin genotype during a period free from any acute illness. A therapeutic trial with oral iron (6mg/kg/day) was given to all children and response was assessed after one month. Ethical approval was obtained from Ethics Committee of University of Kelaniya and data were analysed using SPSS. RESULTS: Sixty-six children (male-54.5%; mean age-20.5±13.9 months) were recruited. Severity of anaemia was mild-38%, moderate-61% and severe- I%. Reported clinical features were: irritability (26%), loss of appetite (6%), fatigue (5%), pica (3%), brittle hair (26%), dry skin (23%), angular stomatitis (2%) and glossitis (2%). Aetiologically, 28 (42.4%) had iron deficiency (ferritinlg/dl after 1 month) was observed in 27 (40 9%).CONCLUSION: Less than half of children with microcytic anaemia had low serum ferritin and only 41 % of children demonstrated a response to a trial of oral iron Thalassaemia trait, especially alpha-thalassaemia is an important cause for microcytic anaemia in asymptomatic children.Item Anaemia among women of child-bearing age: Contributions of alpha and beta-thalassaemia(Sri Lanka Medical Association, 2018) Mettananda, S.; Suranjan, P.D.M.; Fernando, V.R.; Dias, T.D.; Rodrigo, R.; Perera, L.; Mettananda, K.C.D.; Gibbons, R. J.; Premawardhena, A.; Higgs, D. R.INTRODUCTION AND OBJECTIVES: Anaemia during pregnancy is attributed to iron deficiency and pregnant women prescribed iron supplements without investigating for a cause. However, aetiology can be diverse and iron efficiency may contribute only partly. We aimed to describe the aetiology of anaemia among women of child bearing age. METHODS: This descriptive study was conducted at Teaching Hospital, Ragama from June-December 2017. Patient database of deliveries between January 2015 and September 2016 at University Obstetrics Unit was screened (n=3636) to identify women with anaemia (haemoglobinItem Hypervariability in a leading P.vivax malaria vaccine candidate, C-terminal merozoite surface protein 1(Sri Lanka Association for the Advancement of Science, 2000) Manamperi, A.; Holm, I.; Perera, L.; Handunnetti, S.M.; Longacre, S.It is widely accepted that the C-terminal 42 kDa (p42) and 19 kDa (p19) processing fragments of plasmodium Merozoite Surface Protein-1 (MSP-1) are targets of immune protection. To begin to assess the degree of polymorphism in these MSP-1 vaccine candidates, we have investigated the sequence diversity in the p.vivax MSP-1 p42 processing fragment, in 19 natural isolates, from p.vivax infected patients in Kataragama. Sequence analysis of PvMSP-1 p42 in the 19 PCR positive isolates reveald 11 sequences of Belem origin and 8 sequences of Salvador-1 (Sal-1) origin. Among the isolates, these two stains are 98-100% homologous across this region, with one notable exception. This corresponds to a highly polymorphic block of 38 amino acids (24% amino acid homology among isolates). However, this polymorphism appears to be derived largely by re-assorting a dimorphism at each variable position. This type of restricte variability suggests that in spite of its diversity, there may nevertheless be a defined structure for this region of the molecule and that the diversity may be functionally important. Alternatively, it may be specifically designed for maximal effect in immune evasion, as a highly exposed immunogenic loop structure. In striking contrast, a single nucleotide substitution was detected in the cysteine rich C-terminal 19 kDa region, resulting in a lysine to glutamate substitution. This was detected in only one isolate among the 19 isolates investigated for sequence diversity. Since the PvMSP-1 C-terminal antigen is clearly hypervariable in the context of natural infections, a vaccine based on a single version of this antigen, might not induce an effective immunity against the multiple forms. In contrast, the PvMSP-1 p19 domain appears to be well conserved and thus appears to be a considerably more promising vaccine candidate.