MRI RESEARCH DAY 2014
Scientific Sessions
Translating Research into Practice:
A Futuristic Perspective...
30th July 2014
Aldo Castellani Auditorium
Medical Research Institute
Colombo 08
Editorial Board:
Dr. Rajiva de Silva
Dr. Geethani Galagoda
Dr. Dharshan De Silva
Dr. Jude Jayamaha
Ms. Yashora Amarathunga
Ms. Shiromi de Silva
Design:
Dr. Uditha Perera
Contents
Message from the Hon. Minister of Health..........................................................................................................5
Message from the Secretary, Ministry of Health .................................................................................................7
Message from the Director General of Health Services.......................................................................................9
Message from the Deputy Director General (Education, Training & Research) ...............................................11
Message from the Director, Medical Research Institute ....................................................................................13
Academic report of the Research and Ethics Committees .................................................................................15
Programme .........................................................................................................................................................18
1 Oral Presentations .........................................................................................................................................21
OP-1 : Activity pattern of questing ticks in selected areas in Sri Lanka and their significance in
transmitting zoonoses in humans. ......................................................................................................21
OP-2 : Investigation of antimicrobial properties of endophytic fungi isolated from Neoclitsea cassia
("Dawul Kurundu" or "wild cinnamon") ...........................................................................................22
OP-3 : Pestalotin derivatives isolated from secondary metabolites of an endophytic fungus from roots of
Xylocarpus rumphii (Koon thalam / Mudu delun) as anticancer and cytotoxic agents .....................23
OP-4 : An outbreak of Influenza from mid April to June 2013 in Sri Lanka................................................24
OP-5 : Detection of hantavirus infection using commercial immunofluorescence assay (IFA) in Sri Lanka;
A preliminary report. .........................................................................................................................25
OP-6 : Prevalence of anaemia among adult population in the Kilinochchi district ......................................26
OP-7 : Detection of chronic kidney disease (CKD) using serum creatinine and eGFR in an apparently
healthy adult cohort in Sri Lanka.......................................................................................................27
OP-8 : Effect of addition of sitagliptin to patients with traditional oral hypoglycaemic failure: A Sri
Lankan experience .............................................................................................................................28
OP-9 : Prevalence of peripheral arterial disease in a district of Sri Lanka ....................................................29
2 Poster Presentations ......................................................................................................................................30
PP-1 : First Report of Listeria monocytogenes serotypes detected from milk and milk products in Sri
Lanka .................................................................................................................................................30
PP-2 : Antifungal activity of Punica granatum (delum) against dandruff causing fungi ............................31
PP-3 : An audit on “Quality of information of investigation request forms received at the Department of
Virology, Medical Research Institute (MRI)” ...................................................................................32
PP-4 : Rhinocerebral mucormycosis : A case report ....................................................................................33
PP-5 : A study on consumption of human rabies immunoglobulin (HRIG) in government hospitals of Sri
Lanka from 2010 to 2012 ..................................................................................................................34
PP-6 : Molecular detection of dengue and chikungunya viruses in fever patients during the recent
epidemics 2008-2009 in Sri Lanka ....................................................................................................35
PP-7 : Preliminary study of mosquito breeding in selected floral species in the Western and Central
provinces of Sri Lanka with special reference to dengue vectors......................................................36
PP-8 : Description of microorganisms in coloured rains in Sri Lanka 2012 ................................................37
PP-9 : First isolation of Cryptococcus neoformans from sputum in Sri Lanka, presenting as a nonresponding pneumonia .......................................................................................................................38
PP-10 : A case of subcutaneous dirofilariasis manifesting as an abdominal wall lump in a nine month old
child ...................................................................................................................................................39
PP-11 : Chronic rhinofacial conidiobolomycosis - A case report from Sri Lanka .........................................40
PP-12 : Genus Topomyia (Leicester 1908) sub genus Suaymyia from Sri Lanka ..........................................41
PP-13 : Immunoglobulin G immune status and exposure history of measles, mumps and varicella in postgraduate medical trainees ..................................................................................................................42
3 Review Articles.............................................................................................................................................43
3.1
Management of Type 2 Diabetes Mellitus.........................................................................................43
3.2
Diagnosis of von Willebrand disease ................................................................................................54
3.3
Viral Infections in Renal Transplant Recipients ................................................................................62
4 Research Projects of Medical Research Institute 2012-2013........................................................................71
4.1
Ongoing Research Activities .............................................................................................................79
Message from the Hon. Minister of Health
I am delighted to be invited as the Chief Guest at the Inauguration Ceremony of the Research Day of
the Medical Research Institute, Colombo.
Since its establishment in 1900, MRI has strived to strike a balance between a clinical service
provider and the premier center for bio-medical and applied health research. It has successfully
coordinated with diverse medical and allied health disciplines, as well as collaborated with many
local and international organizations to bring forth meaningful research in to the health domain.
Thus it is certainly apt that the theme of this year’s event is “Translating Research into Practice: A
Futuristic Perspective...” As the pinnacle of medical research in Sri Lanka, MRI has highlighted the
importance of improving relevance of research activities based on the needs of the community and
the country as a whole.
I extend my best wishes to the Medical Research Institute on this important day in their quest to
uplift the standards of health research in Sri Lanka.
Hon. Maithripala Sirisena
Minister of Health
MRI Research Day 2014 | Scientific Sessions
5
Message from the Secretary, Ministry of Health
It is with great pleasure that I pen this message on the occasion of the Research Day of the Medical
Research Institute, Colombo, the premier reference medical laboratory in Sri Lanka. This event
serves as a showcase for cutting edge research activities conducted by the MRI in collaboration with
various governmental as well as non-governmental and international agencies.
The Government of Sri Lanka has identified the role of the “Medical Researcher” as a positive
contributor to the health sector as reflected by the increased allocation of resources in the national
budget. As the Secretary to the Ministry of Health I am delighted that the MRI has efficiently
managed these resources to improve the health of Sri Lankans through world-class medical research
so as to achieve the national health goals set by the Ministry.
I extend my good wishes to the Medical Research Institute on this day to hold a successful event
fulfilling the aspirations of all stakeholders.
Mrs. Sudharma Karunaratne
Secretary, Ministry of Health
MRI Research Day 2014 | Scientific Sessions
7
Message from the Director General of Health Services
Medicine is fundamentally different from other sciences that does not possess any general steadfast
principles that are valid under all circumstances and can be applied to all human beings.
Consequently medicine is a science that is experimental in nature. Even the most widely used and
generally accepted treatments should be constantly monitored and analyzed for safety and efficacy.
This can only be achieved through medical research.
The Medical Research Institute has been identified as the hub of medical research based on
laboratory medicine through the Health Master Plan 2007 to 2016. The MRI Research Day, which
reflects the research activities that were carried out during the period of 2012 to 2013, signifies the
commitment of the institution in fulfilling this role.
I extend my compliments to the Medical Research Institute on reaching this important milestone and
wish the event every success.
Dr. Palitha Mahipala
Director General of Health Services
MRI Research Day 2014 | Scientific Sessions
9
Message from the Deputy Director General
(Education, Training & Research)
As the Chairperson of the Research Committee, I am honoured and privileged to be part of the
Research Day of the Medical Research Institute. This event is organized with the aim to promote
ethical research among medical professionals while providing routine health care facilities to the
people of Sri Lanka.
The successful clinician has the ability to interpret the results of research and apply them for the
benefit of patients. Thus, in current context familiarity with research methodology is an essential
skill for competent medical practice.
In accordance with the policy of the government, today Sri Lanka is venturing more and more into
conducting clinical trials. Many of them are multicenter trials. To facilitate these trials professional
and competent ethics committees are needed. This is the way forward.
We consider that creation of research culture among medical and related professionals is our
obligation and responsibility. Thus, the MRI Research Day presents a unique opportunity to all
those interested in medical research to enhance their skills in conducting, documenting and
presenting their findings
Dr. Sunil De Alwis
Deputy Director General (Education, Training & Research)
MRI Research Day 2014 | Scientific Sessions
11
Message from the Director, Medical Research Institute
In the relatively short history of the MRI Research Day, the centerpiece event of the Medical
Research Institute calendar, we have been successful in showcasing the wide range of research
activities undertaken by investigators at all levels.
We continue the tradition in the year 2014, by presenting research activities undertaken by the
dedicated professionals of this esteemed institution in collaboration with various other governmental
and non-governmental agencies. It is hoped that the success of this event inspires our young trainee
researchers to carry on the good work striving to move ideas to possibilities and knowledge, while
looking for opportunities and answers to distinct challenges every day.
It is indeed a privilege to be at the helm of a comprehensive research center with a strong concern
on applied research, contributing significantly to the social and economic development of the
country as per the theme of this year’s event “Translating Research into Practice: A Futuristic
Perspective...”
I take this opportunity to thank our Deputy Director, Dr. Anil Samaranayake who initiated the MRI
Research Day, and the Research Committee for organizing this year’s event.
Dr. Sumith Ananda
Director, Medical Research Institute
MRI Research Day 2014 | Scientific Sessions
13
Academic report of the Research and Ethics Committees
(December 2012 – June 2014)
The Medical Research Institute, in its capacity as the premier research institute for biomedical and allied
fields is dedicated to the aim of improving health and wellbeing of the country. The MRI takes great pride in
its contribution to the advancement of knowledge, through research and training.
The MRI conducts research in various fields in bacteriology, virology, mycology, parasitology, entomology,
immunology, histopathology, haematology, biochemistry, nutrition, pharmacology, natural products and in
animal sciences. It also supports research in areas needing advanced techniques of animal studies and drug
trials. During the past few years, the availability of a research grant from the Treasury has greatly contributed
to the advancement of research at the MRI. These funds are available for all researchers attached to the
Ministry of Health.
During the last 2 years, the Research and Ethics Committees at MRI have seen a great improvement with the
number of research projects evaluated by the research and ethics committees reaching 50 by June 2014.
Fig 1. MRI Research Participation Activities per year
50
50
50
46
44
45
40
35
30
25
20
14
15
15
13
10
10
5
0
2007
2008
2009
2010
2011
2012
2013
2014-June
104 research projects have been evaluated by the Research and Ethics committees from November 2012 to
June 2014. The research fund at MRI was reserved only to researchers at the MRI at the beginning, but later it
was opened up for all researchers working in the Ministry of Health. This resulted in an increase in the
number or research projects involving other fields of studies which are not directly related to the MRI.
Nevertheless, 59% of the research projects have been conducted with the participation of the research staff at
MRI during the past 20 months.
The MRI Research and Ethics committees render an invaluable service to the Post Graduate Institute of
Medicine by funding research projects for trainees in various post graduate fields.
MRI Research Day 2014 | Scientific Sessions
15
Table 1: Contribution of research conducted at MRI
Total number of research projects
Ethics and scientific review – MRI participation
Ethics and scientific review – External
Ethics review only – External
104
61
30
13
Table 2: Sources of funds for the projects
Total number of research projects
Funding from MRI
Funding from other sources
104
68
36
Table 3: Research specialties
Infectious diseases
Public health
Nutrition/Food science
Histopathology/Immunology/Haematology
Natural products
Biochemistry
Medical technology
Medicine/Surgery
Mental health
Animal research
Entomology
35
15
11
9
8
6
6
6
5
2
1
The MRI research committee has opened its doors to students to pursue research of their interest. It has
contributed immensely towards the post graduate education in the country by funding research of post
graduate and undergraduate students. A third of the projects were from such students.
One such student, Rakitha Dilshan Malewana, an year 13 student of Nalanda College, Colombo, has brought
honour to the country by winning the Bronze medal in the International Science Project Olympiad which was
held in Jakarta, Indonesia in 2014. His research was on Catechin Coated Iron Oxide Nanoparticles as an
Anticancer Agent for Leukemia, which was funded by the MRI.
The research projects carried out at MRI have been accepted as of excellent quality by other academic bodies
of the country. These include


16
Establishment of polymerase chain reaction assay to detect active cytomegalovirus replication in the
blood of renal transplant recipients. Nadeeka JS, Wickramasinghe GA. In: The Bulletin of the Sri
Lanka College of Microbiologists. Proceedings of the 21st Annual Scientific Sessions; 2012 August
28-30; Colombo, Sri Lanka; 2012. P. 21 – Best Oral Presentation – Second prize
Molecular evidence of hantavirus infection among clinically suspected patients with haemarrhagic
fever with renal syndrome (HFRS). Muthugala MARV, Manamperi AAPS, Gunasena S, Hapugoda
MD, Goran Butch. In: The Bulletin of the Sri Lanka College of Microbiologists. Proceedings of the
22nd Annual Scientific Sessions; 2012 July 24-26; Colombo, Sri Lanka; 2012. P. 15 – Best Oral
presentation – First prize
Scientific Sessions | MRI Research Day 2014



Development of recombinant protein antigen using bacterial expression system for the detection of
anti-chikungunya (CHIK) antibodies. Athapaththu AMMH, Khanna N, Inouve S, Gunasena S,
Abeywickrama W, Hapugoda M. In: The Bulletin of the Sri Lanka College of Microbiologists.
Proceedings of the 22nd Annual Scientific Sessions; 2012 July 24-26; Colombo, Sri Lanka; 2012. P.
14 – Best Oral presentation – Second prize
Seroprevalence of varicella zoster antibodies in patients with chronic renal failure. Dasanayake
WMDK, Gunawardena S. In: The Bulletin of the Sri Lanka College of Microbiologists. Proceedings
of the 22nd Annual Scientific Sessions; 2012 July 24-26; Colombo, Sri Lanka; 2012. P. 24 – Best
Poster presentation – Second prize
Immunogenicity study following reduced dose (4 doses) intradermal vaccination for anti-rabies post
exposure therapy. Herath HMAK, Wimalaratne O, Perera KADN. In: The Bulletin of the Sri Lanka
College of Microbiologists. Proceedings of the 22nd Annual Scientific Sessions; 2012 July 24-26;
Colombo, Sri Lanka; 2012. P. 17 – Best Poster presentation – 3rd prize
The conclusions from the studies conducted at MRI have been made available to the relevant authorities and
have been utilized to improve the health care system of the country. The cytomegalovirus PCR diagnosis
which was initiated at the MRI is now a part of the diagnostic services of MRI, offering an invaluable service
to renal transplant recipients and patients with other immune deficiencies. Dr HMAK Herath’s
immunogenicity study on reduced dose anti-rabies vaccine, led to the formulation of a national policy
decision of 4 dose anti-rabies vaccine therapy for post exposure prophylaxis of rabies in Sri Lanka. This has
reduced the number of doses of anti-rabies vaccine from 5 to 4, leading to a significant cost saving.
The proceedings of the Research and Ethics committees have been streamlined to provide a better research
background. New formats of the project applications and new application formats for ethics issues in research
involving humans and animals have been prepared. These formats are available on line in the MRI web site.
The Ethics Committee has been a member of the Forum of Ethics Committees of Sri Lanka (FERCSL) which
conducts programs for continuous education in the field of ethics. The members of the Ethics Committee
attend regular training programmes and workshops conducted by the FERCSL. During the past year, 2 such
workshops were conducted by the FERCSL and several members of the Ethics Committee attended the
workshops with the approval of the Deputy Director General (Education, Training and Research) and the
concurrence of the Ministry of Health.
1. Human Research Subject Protection-1 – 11th October 2013
2. Good Clinical Practice and Managing Conflict of Interest - 28th February 2014
These workshops increased the awareness of the participants to the ethical standards and problems faced in
using human subjects for research including drug trials. It also opened up a forum for discussion by meeting
experts in the field of ethics and likeminded researchers.
The Standard Operating Procedures (SOP) of the Ethics Committee has been finalized and accepted by the
members. The committee has recruited 3 non-medical members including a lawyer as members of the
committee. The Ethics Committee at MRI has been accepted by the Ministry of Health.
The MRI Research and Ethics Committees have dedicated themselves to the upliftment and continued support
of medical research in Sri Lanka and continue to work towards the goal of obtaining the membership of the
Federation of Ethics Committees of Asia-Pacific (FERCAP).
Dr Geethani Galagoda
Consultant Virologist
Secretary/Research and Ethics Committees of MRI
MRI Research Day 2014 | Scientific Sessions
17
MRI RESEARCH DAY - SCIENTIFIC SESSIONS
Date
Venue
:
:
30th July 2014
Aldo Castellani Auditorium
Medical Research Institute, Colombo 08
Programme
08.00 - 08.30 am Registration
08.30 - 09.30 am Free Paper Session I
Chairperson: Ms. Kumudu Kulathunga (Senior Research Officer, MRI)
OP-1 Activity pattern of questing ticks in selected areas in Sri Lanka and their significance in
transmitting zoonoses in humans
Liyanaarachchi DR, Rajapakse RPVJ
OP-2 Investigation of antimicrobial properties of endophytic fungi isolated from Neoclitsea
cassia ("Dawul Kurundu" or "wild cinnamon")
Fernando TMM, de Silva ED, Wijayarathna CD, Senadeera SPD, de Silva PGSM, Nicholas
IHV
OP-3 Pestalotin derivatives isolated from secondary metabolites of an endophytic fungus from
roots of Xylocarpus rumphii (Koon thalam / Mudu delun) as anticancer and cytotoxic
agents
Hewage THNRT, Ganihigama DU
09.30 - 10.00 am Inauguration Ceremony
National anthem and traditional lighting of the oil lamp
Welcome address by Director, MRI - Dr. Sumith Ananda
Report of the Secretary, Research & Ethics Committees - Dr. Geethani Galagoda
Address by Director General of Health Services - Dr. Palitha Mahipala
Address by Secretary, Ministry of Health - Mrs. Sudharma Karunaratne
Address by Minister of Health - Hon. Maithripala Sirisena
Vote of thanks by Chairperson, Organizing Committee - Dr. Primali Jayasekera
10.00 - 10.30 am Tea
18
Scientific Sessions | MRI Research Day 2014
10.30 - 11.00 am Free Paper Session II
Chairperson: Dr. Janaki Abeynayake (Consultant Virologist, MRI)
OP-4 An outbreak of Influenza from mid-April to June 2013 in Sri Lanka
Jayamaha CJS, Gunathilaka GDWS, Sanjeewa MDA, Gunatilleka M
OP-5 Detection of hantavirus infection using commercial immunofluorescence assay (IFA) in Sri
Lanka; A preliminary report.
Muthugala MARV, Galagoda GCS, Wimalarathna WKG
11.00 - 11.30 am Plenary Lecture I
Chairperson: Dr Omala Wimalaratne (Consultant Virologist and Vaccinologist)
Primary Immunodeficiency in Sri Lanka: The long march ahead
Dr. Rajiva de Silva MBBS Dip. in Med. Micro. MD
Consultant Immunologist, Medical Research Institute
11.30 -12.30pm Symposium I
Chairpersons: Dr. Darshan De Silva (Consultant Clinical Pharmacologist, MRI)
Dr. Sagarika Samarasinghe (Consultant Parasitologist, MRI)
Are we facing the dawn of the post-antibiotic era?
Dr. Enoka Corea MBBS Dip. in Med. Micro. MD
Senior Lecturer, Department of Microbiology, Faculty of Medicine, University of Colombo
Infection and the future
Dr. Panduka Karunanayake MD(Colombo) FRCP(London) FCCP PgD Appl Sociol.(Col)
Senior Lecturer, Department of Medicine, Faculty of Medicine, University of Colombo
Component Resolved Diagnostics - The Future of Food Allergy
Dr. Neelika Malavige MBBS MRCP(UK) D.Phil(Oxford)
Head/Senior Lecturer, Department of Microbiology, Faculty of Medical Sciences,
University of Sri Jayewardenepura
12.30 - 01.30 pm Lunch
01.30 - 02.15 pm Symposium II - "Use of open resources & information search strategies in BioMedical & Applied Research, Are we aware?”
Chairpersons: Professor Vajira H.W.Dissanayake MBBS, PhD (Professor in Anatomy and Founder
Chairperson, Specialty Board in Biomedical Informatics, University of Colombo)
Dr. Ruwan Gamage PhD (Senior Lecturer, National Institute of Library & Information
Sciences, University of Colombo)
MRI Research Day 2014 | Scientific Sessions
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Resource Person: Dr. Champika Wickramasinghe MBBS, MSc, MD
(Director/Information, Ministry of Health)
Open Access Resources in Medical Sciences and Modular Approach to its
Accessibility: A Sri Lanka Context
Dr(Mrs).W.Senevirathne PhD
Chief Librarian, Open University of Sri Lanka
Open Access Publishing and Web Visibility
Dr. Anusha Wijayaratne PhD
Senior Assistant Librarian (Journals), Open University of Sri Lanka
02.15 - 03.15 pm Free Paper Session III
Chairpersons: Dr. Priyanka Herath (Consultant Haematologist, MRI)
Dr. Lilani Karunanayake (Consultant Clinical Microbiologist, MRI)
OP-6 Prevalence of anaemia among adult population in the Kilinochchi district
Gunatillaka MM, Gunatillaka ND, Gajanakabahu E, Silva TJ, Kumarapeli V, Lankananda
BD, Jayasinghe J, Jayasekara P, Ekanayake P, Peris PI, Muraliharan S, Karthikeyan P,
Samaranayake A
OP-7 Detection of chronic kidney disease (CKD) using serum creatinine and eGFR in an
apparently healthy adult cohort in Sri Lanka
Katulanda GW, Lankananda BD, Gunawardena ADUR, Udayangani DLE, Jayasekara
JKMPN, Jayasekara LPCP, Rathnayaka RMS, Jayasinghe RAJC, Ekanayaka DHP
OP-8 Effect of addition of sitagliptin to patients with traditional oral hypoglycaemic failure: A
Sri Lankan experience
Keerthisena GSP, Dematapitiya BRCM, Neomal SDN, Packianathan JD, Katulanda P
OP-9 Prevalence of peripheral arterial disease in a district of Sri Lanka
Weragoda WAJL, Seneviratne RDA, Weerasingha MC, Wijeyaratne SM, Samaranayaka A
03.15 - 03.45 pm Plenary Lecture II
Chairperson: Dr. Sunethra Gunasena (Consultant Virologist, MRI)
Dengue in Sri Lanka: Where are the new strains coming from?
Dr. Dharshan De Silva BSc (Truman State) PhD (Penn State)
Director, Genetech Research Institute
03.45 pm Conclusion & Presentation of Awards
04.00 pm Tea
20
Scientific Sessions | MRI Research Day 2014
1
Oral Presentations
OP-1 : Activity pattern of questing ticks in selected areas in Sri Lanka and their significance
in transmitting zoonoses in humans.
Liyanaarachchi DR, Rajapakse RPVJ
Department of Veterinary Pathobiology, Faculty of Veterinary Medicine and Animal Science, University of
Peradeniya, Sri Lanka
Introduction
Ticks transmit many zoonotic diseases to humans.
Objectives
Assess the diversity and abundance of questing ticks in relation to ambient temperature, relative humidity and
rainfall in two forests areas in the Kandy district; observe their activity in mornings and evenings, and to
assess ticks in village pastures and in the human body.
Methods
Ticks were collected monthly in the year 2010 by flagging from Hantana and Randenigala forests and in
adjoining pastures from 9 a.m to 12 noon, and in January, April, August and December from 2- 4 p.m.
Temperature, relative humidity and rain fall data were recorded. Questing ticks in domestic pastures were
collected by random visits. Ticks infesting humans in Kandy district were also collected.
Results
Sixteen immature tick species from forest areas, ten from domestic environments, and twelve from humans
were recorded. Ticks density was higher in forest pastures and in certain spots inside the forest. Tick density
was higher during dry periods and evenings. Most abundant species in village pastures and in human ear canal
were immature Demacentor auratus and Amblyomma testudinarium.
Conclusion
Possible environmental factors that affect questing tick density are rain fall and diurnal temperature. Dropping
of engorged ticks from hosts could be higher while resting in the forest or grazing in pastures rather than
when moving across the forest. Presence of very rare Demacentor auratus and Amblyomma testudinarium in
villages and in the human body indicates that they are spreading in domestic environments. It is possible that
they are spread by wild boars. This is may be an indication that many tick borne diseases such as
rickettsiosis, babesiosis, encephalitis and tick paralysis may increase in Sri Lanka in the future. Activities
like camping, hiking, researching, collecting fire wood in the evenings may be high risk activities in the
spread of tick borne diseases.
MRI Research Day 2014 | Scientific Sessions
21
OP-2 : Investigation of antimicrobial properties of endophytic fungi isolated from Neoclitsea
cassia ("Dawul Kurundu" or "wild cinnamon")
Fernando TMM1, de Silva ED1, Wijayarathna CD1, Senadeera SPD2, de Silva PGSM2, Nicholas IHV2
1
Department of Chemistry, Faculty of Science, University of Colombo, Sri Lanka.
Medical Research Institute, Colombo, Sri Lanka.
2
Introduction
Endophytic fungi living asymptotically in plant tissues constitute a valuable source of bioactive secondary
metabolites that can be developed as drugs.
Objectives
To investigate the antimicrobial activity of secondary metabolites of endophytic fungi isolated from Sri
Lankan endemic medicinal plant Neoclitsea cassia using bioassay guided fractionation.
Methodology
Four different types of endophytic fungal strains were isolated from mature leaves and tender/mature bark of
Neoclitsea cassia and named as MF-NC-ML1, MF-NC-TB1, MF-NC-TB2 and MF-NC-TB3. All four fungal
strains were cultured in potato dextrose broth (PDB). Crude extracts of broth and mycelia of each fungal
strain were screened for antibacterial activity against Methicillin Resistant Staphylococcus aureus (MRSA),
Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa using disc diffusion assay. Based on the
result of the antibacterial activity test, fungal strain MF-NC-TB1 was selected for further studies.
The fungal strain MF-NC-TB1 was cultured in PDB (10 L) for 42 days and extracted with EtOAc. The crude
extract was subjected to a solvent/solvent partition scheme; Hexane, CHCl 3, EtOAc, and H2O solubles, where
CHCl3 and EtOAc layers exhibited antibacterial activity. These two layers were combined (159 mg) and
subjected to silica column chromatography and fractions with similar patterns in thin layer chromatography
were pooled together to give five fractions. The most active fraction was subjected to size-exclusion column
chromatography (Sephadex- LH 20) to yield seven fractions.
Results
Antimicrobial activity of each fraction was evaluated using disc diffusion assays against MRSA and E. coli
bacterial strains. Fraction 2 showed activity against MRSA and E. coli with clear zones of inhibitions at 12.0
± 0.5 mm and 10.0 ± 0.5 mm respectively at the concentration of 150 µg per disc.
Conclusion
The endophytic fungal strain MF-NC-TB1 is a promising source of secondary metabolites with antibacterial
activity.
22
Scientific Sessions | MRI Research Day 2014
OP-3 : Pestalotin derivatives isolated from secondary metabolites of an endophytic fungus
from roots of Xylocarpus rumphii (Koon thalam / Mudu delun) as anticancer and
cytotoxic agents
Hewage THNRT1,2, Ganihigama DU 2
1
Department of Biochemistry, Medical Research Institute, Colombo 08.
2
Chemical Biology Program, Chulabhorn Graduate Institute (CGI), Bangkok 10210.
Introduction
Endophytic fungi are rich sources of biologically active natural products. Particular endophytic fungi can
produce pharmaceutically important secondary metabolites such as paclitaxel and camptothecin.
Objective
Isolate, characterize, and investigate the bioactivities of secondary metabolites produced by endophytic fungal
strain isolated from the roots of Xylocarpus rumphii.
Method
Fungal cultures were inoculated aseptically in 20 Erlenmeyer flasks each containing 250 ml of potato dextrose
broth medium containing 25% seawater. After 30 days, the fermented fungus was extracted to ethyl acetate
and separated using Sephadex LH-20 column chromatography followed by C18 RP-HPLC to obtain (-)
pestalotin (compound 1) and 6-(1-hydroxypentyl)-4-methoxy-2H-pyran-2-one (compound 2).
Cytotoxic and anticancer properties were evaluated for compounds 1 and 2. Cytotoxicity was examined
against adhesive cell lines of HepG2 (human hepatocellular carcinoma), HuCCA-1 (human
cholangiocarcinoma), and A549 (human alveolar epithelial cells) using MTT (3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide) assay, and non-adhesive cell line MOLT-3 (human acute T lymphoblastic
leukemia) employing XTT ((2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide)
assay. Anticancer effect was evaluated by using scavenging of DPPH free radicals, xanthine oxidase (IXO),
xanthine/xanthine oxidase (XXO), lipoxygenase inhibitory (LOX), and aromatase inhibitory (AIA) assays.
The structures of isolated compounds were elucidated and confirmed by a combination of spectroscopic
methods (1D, 2D NMR, IR, UV, and MS) and optical rotations.
Results
Both compounds 1 and 2 exhibited IC50 values in the range of 43.5-50.0 µg/ml against HuCCA-1, A549,
HepG2, and MOLT-3 cell lines. Compound 2 showed inhibition of superoxide anion radical formation (IXO)
assay with IC50 value of 357.2 µM.
Compound 1 showed a negative optical rotation, which was similar to that of (-) pestalotin. Compound 2
showed a positive optical rotation, which was confirmed to that of 6-(1-hydroxypentyl)-4-methoxy-2H-pyran2-one.
Conclusion
Compounds 1 and 2 showed weak cytotoxic activity while compound 2 showed anticancer properties.
Acknowledgement: Dr. P Kittakoop (Chemical Biology Program, CGI)
MRI Research Day 2014 | Scientific Sessions
23
OP-4 : An outbreak of Influenza from mid April to June 2013 in Sri Lanka
Jayamaha CJS, Gunathilaka GDWS, Sanjeewa MDA, Gunatilleka M
National Influenza Centre, Department of Virology, Medical Research Institute, Colombo
Introduction
Influenza viruses are known to cause explosive outbreaks in the community.
Objectives
To report morbidity, mortality and types/subtypes during an outbreak of influenza
Methods
Study period was from 13/04/2013 to 30/06/2013. RNA was extracted from respiratory specimens and was
subjected to influenza A/B real-time PCR. Influenza A positive samples were further subtyped. Demographic
and clinical details were analysed.
Results
Of 1580 clinical samples received 1336 were tested. Of the samples sent, 28.5% were not in accordance with
national guidelines on influenza laboratory investigations. Of tested samples, 513 (38.39%) were positive for
influenza A (n=362, 70.57%) and influenza B (n=151, 29.43%). Of Influenza A, pandemic H1N1 2009 strain
was detected in 225 (62.5%) while H3N2 was detected in 13 (3.6%) samples. Of the influenza A strains, 51
(14.1%) were not typable (non H1, non H3) and 73 were not typed. Age distribution was, < 1 year - 4.8%, 1
to 4 years - 9.3%, 5 to 9 years - 4.6%, 10 to 14 years - 3.6%, 15 to 49 years - 57.8%, 50 to 65 years - 14.5%
and >65 years - 5.5%. Average age was 46.5 (range - day 1 to 87) years. There were 143 pregnant females
infected with influenza (A=114, B =29). Out of 15 deaths, 12 were due to influenza A and 3 were due to
influenza B. The age distribution of the patients who died were 17 to 89 years, while the majority were from
15 to 49 year age group. Of the deaths, four had predisposing lung disorders and five were pregnant.
Conclusions
Influenza A pandemic H1N1 2009 strain (predominantly) and influenza B caused the respiratory disease
outbreak with a significant number of maternal deaths. Highest morbidity and mortality was seen in the 15 to
49 year age group.
24
Scientific Sessions | MRI Research Day 2014
OP-5 : Detection of hantavirus infection using commercial immunofluorescence assay (IFA)
in Sri Lanka; A preliminary report.
Muthugala MARV, Galagoda GCS, Wimalarathna WKG
Department of Virology, Medical Research Institute, Colombo 08
Introduction
Hantavirus infection is an emerging zoonotic viral infection. In Asia and the western Pacific, hantavirus
causes haemorrhagic fever with renal syndrome (HFRS) which appears clinically similar to leptospirosis.
Detection of hantavirus specific IgM antibodies in patients’ serum by using immunofluorescence assay (IFA)
can be used for the early diagnosis of this infection.
Objectives
To detect hantavirus infection in clinically suspected patients with HFRS by using a commercial IFA assay
To describe socio-demographic and clinical features of hantavirus infection in Sri Lankan patients
Method
Seventy two clinically suspected HFRS patients according to the accepted case definition, from April 2013 to
March 2014, were included in the study. Blood samples were tested for specific IgM antibodies against
hantavirus using a commercial IFA kit. Patients’ socio-demographic and clinical details were collected and
analyzed.
Results
Of tested samples 05 (06.94%) were positive for hantavirus specific IgM. All the hantavirus positive patients
had a history of working in paddy fields 2-3 week prior to the onset of the disease. All were males and were
aged between 20-40 years.
In addition to classical clinical feature of HFRS (fever, thrombocytopaenia and nephritis), 04 (80%)
hantavirus positive patients had signs and symptoms of liver involvement and 01(20%) patient had a
pulmonary haemorrhage.
Conclusion
Serological evidence of hantavirus infection was detected in clinically suspected patients with HFRS in Sri
Lanka. Further studies are required to describe the epidemiology of the disease in the country.
Acknowledgement: WHO (WHO Biennium project SESRL1206172)
MRI Research Day 2014 | Scientific Sessions
25
OP-6 : Prevalence of anaemia among adult population in the Kilinochchi district
Gunatillaka MM1, Gunatillaka ND2, Gajanakabahu E3, Silva TJ1, Kumarapeli V4, Lankananda BD1,
Jayasinghe J1, Jayasekara P1, Ekanayake P1, Peris PI1, Muraliharan S5, Karthikeyan P6, Samaranayake A1.
1
Medical Research Institute Colombo,
University of Sydney, Australia,
3
District General Hospital Kilinochchi,
4
Mental Hospital, Mulleriyawa.
5
MOH Office Kilinochchi,
6
RDHS Office Kilinochchi
2
Introduction
Anaemia is an important parameter in assessing the health status of people living in a particular geographical
area. This basic data is not available in the former conflict zones such as the Kilinochchi district in Sri Lanka.
Objectives
To determine the prevalence of anaemia among the adult population of Kilinochchi district in Sri Lanka
Methods
A sample of 863 individuals from the general population of all four MOH areas was selected, using
multistage proportional random allocation. Blood haemoglobin concentration was estimated by the WHO
recommended haemoglobin cyanide method and blood haematocrit was analyzed manually. Reference
standards and quality control samples in duplicate were used for each batch. Samples with blood haemoglobin
values (<80mg/dl) were reconfirmed.
Results
A total of 847 samples were analyzed. Sixteen samples were rejected due to pre-analytical errors. The age
ranged from 21 to 80 years and sex distribution was 447 (52.7 %) males to 400 (47.3%) females. The
prevalence of anaemia in the study population was 232/847 (27.4%) and of that 138/232 (59.5%) were
females. The prevalence of severe anaemia in the total population was 12/836 (1.4%) and in those less than 40
years of age was 4/399 (1%). Anaemia in the age category from 60 - 80 years was 61/135 (45.2%), and
33/185 (17.8%) in the 21-30 years age category.
Conclusion
The prevalence of anaemia in the study population in Kilinochchi is 27.4% but severe anaemia is limited to
1.4%.
26
Scientific Sessions | MRI Research Day 2014
OP-7 : Detection of chronic kidney disease (CKD) using serum creatinine and eGFR in an
apparently healthy adult cohort in Sri Lanka
Katulanda GW, Lankananda BD, Gunawardena ADUR, Udayangani DLE, Jayasekara JKMPN, Jayasekara
LPCP, Rathnayaka RMS, Jayasinghe RAJC, Ekanayaka DHP
Department of Biochemistry, Medical Research Institute, Colombo 08
Introduction
The prevalence of CKD is high in Sri Lanka. Serum creatinine is not sensitive enough in the early stages of
renal impairment while estimation of GFR using creatinine clearance is cumbersome and impractical.
Estimated glomerular filtration rate (eGFR) obtained using algorithms is emerging as a reliable marker of
early CKD. The modification of diet in renal disease (MDRD) formula was commonly used. Recently chronic
kidney disease – epidemiology collaboration (CKD-EPI) appeared as a better marker. We compared both
formulae in an apparently healthy cohort.
Objective
1. To compare eGFR and serum creatinine to detect early CKD in an apparently healthy adult group.
2. To compare the CKD- EPI and MDRD equations to identify CKD in the same cohort.
Method
159 apparently healthy adult volunteers from the staff of the Medical Research Institute gave venous blood on
request within a day. Their age and sex were recorded. Creatinine was measured and eGFR was calculated
using the MDRD and CKD-EPI formulae.
Results
The mean age was 40.3 years (SD = 12.9 years). 73 of them were males. 7.5% of the population had
creatinine levels above the sex specific reference limits. MDRD and CKD-EPI equations detected 9.4% and
8.8% of population respectively, as having CKD (Stage 3). The MDRD equation recognized 7.5% while
CKD-EPI equation recognized 20.8%, to have a normal GFR.
Stages of CKD by MDRD and CKD-EPI formula
CKD
GFR (mL/min/1.73m2)
Stage-3
Stage-2
Stage-1 (normal)
30-59
60-89
>90
eGFR by MDRD
15 (9.4%)
132 (83.0%)
12 (7.5%)
eGFR by CKD-EPI
14 (8.8%)
112 (70.4%)
33 (20.8%)
Conclusions
eGFR detects early CKD despite serum creatinine being within normal limits in apparently healthy adults in
Sri Lanka. Therefore eGFR should be widely used to detect early CKD among apparently healthy adults in
Sri Lanka. MDRD equation recognizes more people as having CKD compared to the CKD-EPI formula. We
need more studies to select the better equation out of the two or develop a new equation for Sri Lankans.
MRI Research Day 2014 | Scientific Sessions
27
OP-8 : Effect of addition of sitagliptin to patients with traditional oral hypoglycaemic failure:
A Sri Lankan experience
Keerthisena GSP, Dematapitiya BRCM, Neomal SDN, Packianathan JD, Katulanda P
Diabetes Research Unit, Faculty of Medicine, University of Colombo, Colombo7
Introduction
Poorly controlled diabetes is very common. Sitagliptin is a novel oral hypoglycaemic agent (OHA) which is
proven to be efficacious in improving glycaemic control in patients with poorly controlled diabetes. But its
efficacy has not been assessed in a Sri Lankan setting.
Objectives
The aim of this study was to evaluate the effect of sitagliptin as an add-on therapy for patients with failure of
traditional OHAs (metformin and sulfonylurea with or without a glitazone) in achieving glycaemic control in
a Sri Lankan setting.
Method
This clinical audit was conducted at a private sector consultation. All patients who were commenced on
sitagliptin due to unsatisfactory glycaemic control (HbA1c >7%) despite being on at least two conventional
OHAs were evaluated. Data were collected both retrospectively and prospectively. Data of 105 patients are
presented in this preliminary study. Data were analysed using SPSS version 16.0.
Results
In 105 patients (mean age 55.72 (±11.58) years, males - 54.8%, mean duration of diabetes - 12.21 (±6.36)
years) mean fasting plasma glucose (FPG) at baseline, 03, 06 and 09 months were 167.79 (±43.57) mg/dL,
126.18 (±31.12) mg/dL, 131.74 (±33.92) mg/dL and 128.66 (±27.86) mg/dL respectively. Mean HbA1c at
baseline, 03, 06 and 09 months were 9.05 (±1.27) %, 7.66 (±0.91) %, 7.67 (±1.05) % and 7.46 (±0.82) %
respectively. A statistically significant difference was observed in both mean FPG and mean HbA1c levels at
03, 06 and 09 months when compared to baseline values (p<0.001 at each occasion). Effect on body weight
did not show a significant difference at all 03 time points (p=0.26, p=0.37, p= 0.38).
Conclusions
Addition of sitagliptin to OHAs significantly improves HbA1c and FPG and the effects are sustainable for 09
months. There was no significant weight gain despite improvement of glycaemic control.
28
Scientific Sessions | MRI Research Day 2014
OP-9 : Prevalence of peripheral arterial disease in a district of Sri Lanka
Weragoda WAJL1, Seneviratne RDA2, Weerasingha MC2, Wijeyaratne SM3, Samaranayaka A4
1
Ministry of Health
Department of Community Medicine, Faculty of Medicine, University of Colombo
3
Department of Surgery, Faculty of Medicine, University of Colombo
4
Medical Research Institute
2
Introduction
Peripheral arterial disease (PAD) is a slowly progressive atherosclerotic disease characterized by occlusion of
lower limb arteries ultimately causing acute or chronic limb ischemia. PAD is increasingly recognized as a
health burden worldwide. Epidemiological information on peripheral arterial disease is not available in Sri
Lanka.
Objective
To estimate the prevalence of peripheral arterial disease among adults aged 40 -74 years in the district of
Gampaha.
Methods
A community based descriptive cross sectional study was carried out in Gampaha district in 2012/13. Multi
stage probability proportionate to size cluster sampling method was used. A sample of 2912 adults aged 40-74
years with equal number of males and females was selected. Ankle-brachial pressure index (ABPI) was
measured using a handheld arterial Doppler instrument on all of the respondents. PAD was defined as an
ABPI ≤ 0.89.
Results
The proportion of those having PAD was 3.2% (n=88). An adjustment was made for the sensitivity of the
arterial Doppler. Adjusted prevalence of PAD among age group of 40-74 years was 3.6% (CI 2.9% – 4.3%).
It was 3.3% in males and 3.1% in females. There was a statistically significant trend in occurrence of PAD
with age (χ2 trend = 109.4, df=1, p< 0.001).
Prevalence of PAD by age group
Age group (years)
40-44
45-49
50-54
55-59
60-64
65-69
70-74
0%
1.0 %
2.0%
2.3%
4.3%
8.8%
13.6%
Prevalence
Conclusion
Although there is less attention at present PAD is becoming a public health concern in Sri Lanka particularly
with an aging population.
MRI Research Day 2014 | Scientific Sessions
29
2
Poster Presentations
PP-1 : First Report of Listeria monocytogenes serotypes detected from milk and milk
products in Sri Lanka
Wijendra, WAS1, Kulatunga, KAKC2, and Ramesh, R3
1
Department of Mycology, 2Department of Bacteriology & 3Department of Molecular Biology,
Medical Research Institute, Colombo 08, Sri Lanka.
Introduction
Listeria monocytogenes is a food borne pathogen that can cause serious invasive disease in humans.
Contamination of milk and milk products with L. monocytogenes is a serious problem to the world and to
developing countries like Sri Lanka. Even the presence of low numbers is a potential risk since this
organism is capable of multiplying at ambient and refrigerated conditions.
Objective
To detect the circulating serotypes in dairy industries using molecular methods and to trace the lineage of
these serotypes
Methods
Raw milk, pasteurized milk, ice cream, curd, yogurt and cheese samples were collected from many parts
of the country and were tested for the presence of L. monocytogenes and study the serotype. We
developed an early, rapid and cost effective PCR detection system and used a more reliable molecular
serotyping selected from the current molecular serotyping methods.
Results
A total of 266 raw milk and dairy product samples from all over the country were tested by the molecular
method. Forty five of raw milk, 10 of ice cream, 10 of pasteurized milk, 8 of curd, 4 of cheese and 3 of
yoghurt samples were contaminated with L. monocytogenes. Among those, 61.51%, 11.53% and 4%
belonged to serotypes 1/2a, 1/2b and, 1/2c respectively.
Conclusion
L. monocytogenes isolates in raw milk have been previously linked to multiple human listeriosis
outbreaks. The majority of large outbreaks have been caused by serovars 1/2a and 1/2b (Kathariou, 2000);
Jacquet et al., 2002; Zhang and Knabel, 2005). In the dairy industry, continued efforts to control the
presence of this pathogen in the production chain are urged and are critical to ensure the safety of these
products. This is the first report about the serotypes of L. monocytogenes circulating in Sri Lanka.
30
Scientific Sessions | MRI Research Day 2014
PP-2 : Antifungal activity of Punica granatum (delum) against dandruff causing fungi
Wijendra WAS 1, Perera DFTN2, and Fernando KMEP2
1
Department of Mycology, Medical Research Institute, Colombo 08, Sri Lanka
2
Department of Botany, Faculty of Applied Sciences, University of Sri Jayewardenepura,
Nugegoda, Sri Lanka
Introduction
Dandruff is caused by Malassezia species and complete control of infection is difficult. Punica granatum
plant is used in traditional medicine to cure many skin diseases.
Objective
To determine the potential phytochemicals in P. granatum against dandruff causing fungi
Methods
Aqueous and methanol crude extracts of leaves from P. granatum were used to screen for bioactive
phytochemicals against two standard cultures (Malassezia furfur CBS-1878 and Malassezia restricta
CBS-7877). The antifungal activity of crude extracts was tested using agar well diffusion method. The
chosen crude extract was separated into four fractions; hexane, chloroform, ethyl acetate and aqueous.
The fraction which possessed the highest antifungal activity was selected. The phytochemicals present in
the chosen fraction were separated using thin layer chromatography (TLC) and were detected under UV
light. Contact bio-autography was performed using the detected spots against the test organisms to
determine the growth inhibitory activities. Finally, the secondary metabolites that were separated out by
TLC, which exhibited antifungal properties, were identified using specific spray reagents.
Results
Methanol crude extract revealed the highest antifungal activity (35.5 mm) against M. furfur CBS-1878 in
the initial screening. Ethyl acetate fraction exhibited the highest antifungal activity (36.6 mm) against M.
furfur CBS-1878. When the separated phytochemicals which exhibited antifungal activity were exposed
to different spray reagents, the presence of saponins, steroids and flavonoids were detected.
Conclusion
Punica granatum has antifungal activity against some fungi which causes dandruff.
MRI Research Day 2014 | Scientific Sessions
31
PP-3 : An audit on “Quality of information of investigation request forms received at the
Department of Virology, Medical Research Institute (MRI)”
Muthugala MARV, Nanayakkara SSJ, Gunasena S
Department of Virology, Medical Research Institute, Colombo 08.
Introduction
The Dept. of Virology, MRI provides a wide range of virological diagnostic services to the country. Most
of these highly specialized tests are performed only at the MRI. Information given in the request forms
which accompany the sample is essential for performing the appropriate diagnostic test and has an effect
on the validity of the results. It is also essential to that the results are sent the correct patient.
Objective
To evaluate the quality of information of the investigation request forms received at the Dept. of
Virology, MRI
Methods
All the request forms received from 20th January to 01st March 2014 for routine diagnosis were analyzed.
Information which should be filled in MRI request form was taken as the accepted standard. Request
forms for existing surveillance studies were excluded from the audit.
Results
Of 1002 request forms analyzed, 73.34% were on MRI forms and 15.15% were on hospital request forms,
rest (11.51%) were not on acceptable request forms. Information on the patient’s identity (name, BHT or
clinic number) was not recorded in 1.2% of the forms and 13.93% of the forms did not identify the
requesting health institution. Of the 61.27% formed that recorded a clinical history, only 58.78% had
given an adequate clinical history. The type of sample was not indicated in 12.12% and only 87.88%
contained the signature or name of the authorizing person. The laboratory test was not specified in
20.60% and in 17.58% we were unable to decide on the appropriate laboratory test based on clinical
history given on the request form.
Conclusion
There were significant deficiencies in the quality of information given on investigation request forms.
Medical staff should be educated on the importance of information given on request forms to achieve
maximum utilization of laboratory services.
32
Scientific Sessions | MRI Research Day 2014
PP-4 : Rhinocerebral mucormycosis : A case report
Gunasekera GCS1, Patabendige CGUA1, Jayasekera PI2, Dayasena RP1
1
National Hospital of Sri Lanka, Colombo 10, 2Medical Research Institute, Colombo 08
Rhinocerebral mucormycosis is a life threatening fungal infection occurring in humans, caused by the
ubiquitous saprophytic fungi of the order Mucorales. Timely diagnosis in patients with predisposing
factors leading to immunosuppression is of great importance in reducing morbidity and mortality.
We present a case of rhinocerebral mucormycosis involving paranasal sinuses and orbit, which
manifested as unilateral facial numbness/pain, ophthalmoplegia, ptosis and proptosis. The patient had
type II diabetes mellitus for nine years and was also a heavy alcoholic. A high level of clinical suspicion
and imaging studies guided the clinical diagnosis. Microbiological and histopathological diagnoses were
confirmatory. Direct visualization of broad, aseptate fungal filaments and isolating the fungus which had
morphological features of Rhizopus spp. were diagnostic. Surgical removal of the fungal material on
several occasions, prompt commencement of systemic anti-fungal therapy with intravenous amphotericinB and maintaining a good glycaemic control made the management, successful. The adverse effects of the
drug were tackled with close monitoring of renal/liver function tests and serum K2+/Mg2+ levels.
After thirty days of systemic amphotericin-B therapy, our patient achieved clinical recovery. As the
duration of treatment is highly individualized depending on repeat imaging and negative
biopsies/cultures, it is yet to be decided.
Conclusion
A high level of clinical suspicion is essential to make a timely diagnosis of rhinocerebral mucormycosis.
Comprehensive management includes correction of predisposing factors, surgical de-bulking and
systemic antifungal treatment.
MRI Research Day 2014 | Scientific Sessions
33
PP-5 : A study on consumption of human rabies immunoglobulin (HRIG) in government
hospitals of Sri Lanka from 2010 to 2012
Amarasinghe WDNL, Wimalaratne O, Nanayakkara S, Sumathipala TKGS, De Costa MGK
Department of Rabies & Vaccine Quality Control, Medical Research Institute, Colombo 08
Introduction
Sri Lanka is a country endemic for rabies and the government spends over Rs. 650 million to control
rabies annually. The average cost of HRIG is Rs. 30,000.00 for an average 60 Kg person.
Main Objective
To analyze the consumption of HRIG in government hospitals of Sri Lanka by the number of patients
treated & to observe the pattern of usage during the period from 2010 to 2012.
Methods
Data was extracted from the patient information forms for HRIG administration sent from the government
hospitals to the Medical Research Institute from 1st of January 2010 to 31st of December 2012. Deviation
from the protocol for anti-rabies post exposure therapy was considered as unnecessary usage.
Results
1896, 2160 and 2186 patients have received HRIG during 2010, 2011 and 2012, respectively. During the
period, HRIG has been used for 3669 (60%) stray dog and cat bites and 1477 (24%) for domestic animal
bites. Squirrel bites were the most common among wild animal bites presented. HRIG has been used
unnecessarily on 60 (3%) patients in 2010, 103 (5%) in 2011 and 170 (8%) in 2012.
Conclusions
Annual consumption and unnecessary usage of HRIG have been increasing from 2010 to 2012. A
significant proportion of HRIG has been used on stray dog and cat bites.
Recommendations
HRIG should not be used unnecessarily and to achieve this, the protocol for anti-rabies post exposure
therapy should be strictly followed. Expert advice should be sought when deciding on administering
HRIG. Medical officers at rabies treatment units should be continuously updated on appropriate usage of
HRIG. Other methods like control of stray dog and cat population and the concept of responsible pet
ownership should be promoted among the public.
34
Scientific Sessions | MRI Research Day 2014
PP-6 : Molecular detection of dengue and chikungunya viruses in fever patients during the
recent epidemics 2008-2009 in Sri Lanka
Kuruppuarachchi KGR1, Perera MGAN2, Gunasena S3, Ramesh R4
1
Department of Immunology, 3Department of Virology, 4Department of Molecular Biology, Medical
Research Institute, Colombo 08;
2
Faculty of Applied Sciences, Sabaragamuwa University of Sri Lanka
Introduction
Dengue and chikungunya are among the most common vector born viral diseases of humans. WHO
reported 37,667 chikungunya cases from Sri Lanka during 2001-2007. Sri Lanka has been affected by
dengue epidemics with the number of cases increasing with each epidemic. Since complications of
dengue can be potentially fatal, differential diagnosis of these two infections is essential for clinical
management, prevention & control.
Objective
To determine whether the causative agents of dengue and chikungunya or both were responsible for the
epidemic in 2008/2009
Method
Peripheral venous blood samples were obtained from suspected patients for the diagnosis of dengue and
chikungunya during the outbreak period. These included the samples sent from clinics, military camps
and hospitals in different parts of the island. Samples collected within 1-4 days of fever were subjected to
molecular diagnosis of dengue, chikungunya or both at the Department of Molecular Biology, MRI.
Serum was separated and viral RNA was extracted from serum using silica (personal communication Dr.
A. D. Silva, Yale University, School of Medicine). RT-PCR was done according to the method of
Hasebe, et. al (J. Med. Virol. 67:370-374 (2002)) with the modification of using enzymes instead of bead
coated enzymes.
Results
30 and 47 samples were tested for chikungunya virus and dengue virus respectively and 3 samples were
tested for both viruses. 21/30 samples tested positive for chikungunya virus and 12/47 tested positive for
dengue virus and none tested positive for both viruses. Chikungunya virus was detected in districts
Rathnapura (10), Monaragala (3), Ampara (3), Kurunegala (4) and Kandy (1) while the dengue virus was
detected in Rathnapura (3), Batticaloa (8) and Gampaha (1) districts.
Conclusion
The epidemic of chikungunya is spreading over the areas Embilipitiya, Monaragala, Polonnaruwa and
Kalmunai. On the basis of the above conclusion, health officials recommended to initiate actions for further
prevention and control of an epidemic of chikungunya in the Embilipitiya area of Ratnapura District.
MRI Research Day 2014 | Scientific Sessions
35
PP-7 : Preliminary study of mosquito breeding in selected floral species in the Western and
Central provinces of Sri Lanka with special reference to dengue vectors
Jayarathne R, Piyadasa TA, Ranasinghe P, Sunil Shantha D, Weerasinghe IS
Medical Research Institute, Colombo 08
Introduction
Mosquitoes breed in various habitats such as ponds, marshes, ditches, pools, drains, water containers and
other similar water collections. Different genera of mosquitoes have shown specific breeding preference.
The vectors of Dengue/DHF, Aedes aegypti and Aedes albopictus breed in man-made or natural container
habitats, of which plants are one natural breeding site. The term “phytotelmata” (plant with waters) was
given by Varga (1928) to describe bodies of water held by plants.
Objective
To ascertain the extent of invasion of phytotelmata by dengue vectors for control purposes
Methodology
Mosquito breeding was examined in randomly selected 766 number of phytotelmata such as leaf axils in
Anana spp, Bromelia spp, Alocasia spp, Pandanus spp, Drasina spp, tree holes and bamboo stumps of
selected sites in Gampaha, Kandy, Matale and Nuwaraeliya districts from May to September 2011.
Results
Twelve mosquito species belonging to five genera (Culex, Aedes, Tripteroides, Malaya and Armigeres)
were found. Aedes albopictus was found in Anana spp (46.2%), Bromelia spp (47.2%), tree holes
(40.2%), bamboo stumps (32.6%), Alocasia spp (27.4%), Pandanus spp (10.8%) and Drasina spp (1.8%).
Malaya spp were found in Pandanus spp (53.1%) and Alocasia spp (66.98%). Tripteroides spp were
found in Drasina spp (20%) and bamboo stumps (62.3%). A total of 112 tree holes were examined, 55%
of them were in Delonix regia (Mai Mara) trees and 53.2% of those were positive for Aedes albopictus.
No positive correlation was observed between water level and larval density. The pH of the breeding sites
occupied by Aedes larvae ranged between 6.5 to 6.9.
Conclusion
Aedes albopictus was found breeding in almost all the phytotelmata that examined and attention should be
made to these breeding sites during dengue vector control programs.
36
Scientific Sessions | MRI Research Day 2014
PP-8 : Description of microorganisms in coloured rains in Sri Lanka 2012
Samaranayake A., Pathirage S, Wickramarathne K., Karunanayake S.P.D., and Perera M.U.T.
Medical Research Institute, Colombo 08
Objective
To describe the variety of microorganisms present in the different episodes of coloured rain occurred in
Sri Lanka in 2012
Methods
Several episodes of coloured rain were reported in the Central and Southern Provinces of Sri Lanka
during late November and December 2012. Samples of coloured rain water were obtained through field
health staff in different locations and were placed directly on sterile microscope slides and examined
under the light microscope and Transmitting Electron Microscope (TEM).
Results
Different types of unicellular living organisms were present and most of their biological features were
similar to diatoms. They were clearly distinguishable from light microscope images of morphologically
closest known organism, Trentopohlia, since red colour in rain cells is visible throughout the entirety of
the cell including the outer wall, and it is not caused by localized carotenoids. The cross-sections of cells
revealed unusually thick outer walls. TEM showed outer cell walls unusually rich in uranium and a
nuclear region with a strong deficit or absence of phosphorus. These organisms could not be identified as
any known species already documented.
Conclusion
The presence of microbial cells of extraterrestrial origin in the red rain of Kerala has been well
documented. There is evidence that they were carried into the atmosphere by a meteorite. Although these
preliminary results do not conclusively prove that the coloured rain cells are of extraterrestrial origin, they
appear to be strongly suggestive. Alternatively, it has to be concluded that they represent a hitherto
unrecognized form of terrestrial life.
MRI Research Day 2014 | Scientific Sessions
37
PP-9 : First isolation of Cryptococcus neoformans from sputum in Sri Lanka, presenting as
a non-responding pneumonia
Wickramasinghe D1, Bowattage S1, Jayasekera PI2, Dhammika RAHM1, Wijesundara WMSK1,
Malkanthi MA2
1
Polonnaruwa General Hospital, Polonnaruwa
2
Department of Mycology, Medical Research Institute, Colombo
Introduction:
Cryptococcus neoformans is an encapsulated yeast. The main port of entry is the respiratory tract and
lungs are the primary site of infection. We describe a case of pulmonary cryptococcosis in a patient with
chronic kidney disease and uncontrolled diabetes mellitus.
Case History:
A 59 year old man with uncontrolled diabetes and acute on chronic renal disease presented with cough
with whitish sputum of 7 days duration with no fever. He was on treatment for bronchial asthma,
ischeamic heart disease, diabetes mellitus and heart failure.
On examination, he was pale, afebrile, tachypnoeic with a respiratory rate of 26/minute. No abnormalities
of the central nervous system were detected. His chest x-ray revealed bilateral pulmonary shadows
predominantly on the right side. Laboratory investigations revealed WBC- 17,000, neutrophil count 73%
with very low (< 15,000) platelets, serum creatinine - 4.62 mg/dl, urea - 36.85 mmol/l, normal serum
electrolytes, slightly elevated liver transaminases, with normal alkaline phosphatase and serum bilirubin.
Sputum culture was not done. His symptoms continued despite 7 days of broad spectrum antibiotic
treatment.
His CXR and CT chest reports revealed a diffuse fungal infection (not a fungal ball). Fluconazole was
added to antibiotics. Patient died 1 day before, Cryptococcus neoformans was isolated from early morning
sputum sample (yeast forms were seen in sputum gram stain). Blood culture was negative.
Conclusion:
Early diagnosis and early treatment is important for a good outcome of unusual causes like Cryptococcus
neoformans infection.
38
Scientific Sessions | MRI Research Day 2014
PP-10 : A case of subcutaneous dirofilariasis manifesting as an abdominal wall lump in a
nine month old child
Wickramasinghe D1, Gunasekara P1, Edirisinghe JS2
1
Teaching Hospital, Anuradhapura
Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka, Anuradhapura
2
Introduction
Dirofilariasis, a disease commonly found in carnivorous mammals, is uncommon in humans. The number
of cases has increased and now it is considered as an emerging zoonoses.
We report a case of dirofilariasis in the subcutaneous tissue of the abdominal wall in a nine month old
child.
Case report
A 9 month old female child from north central province in Sri Lanka, presented with a lump (1.5 cm x 1.5
cm) in the subcutaneous tissue of the abdominal wall. The mother had noticed a firm, single swelling for
several days. The skin overlying the swelling was intact and showed no blister. There was no
lymphadenopathy. Examination of the peripheral blood did not show eosinophilia.
The clinical diagnosis was a lipoma. The lesion was excised and was sent for histopathology. The
specimen received was a pale grey nodular piece of tissue measuring 20x20x18 mm. Cut surface showed
a central cavity containing a ball of worms. The specimen was routinely processed and 4-5 μm thick
sections were obtained and stained with H&E. Sections showed a fragmented parasite surrounded by a
thick laminated cuticle with fine external longitudinal ridges. Underneath the cuticle, a thick
circumferential muscular layer interrupted by two lateral cords was seen. Some sections showed portions
of the intestine as well as the uterine cavity. The features were consistent with Dirofilaria repens.
The infection is more common in adults. However, in Sri Lanka, we commonly encounter in children but
in this case it is in a nine months old child.
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PP-11 : Chronic rhinofacial conidiobolomycosis - A case report from Sri Lanka
De Mel P1, Perera LSJ1, Fernando WSD1, Jayasekera PI2, Perera PD, Malkanthi MA2
1
2
District General Hospital, Negombo
Department of Mycology, Medical Research institute, Colombo
Case report
We report a case of previously healthy, young male with unilateral, progressive, firm, painless swelling of
upper lip causing facial disfigurement and progressive nasal obstruction. Clinical examination revealed
hard nodular sub-mucous lesions in the upper lip with bulky nasal turbinates. No involvement of local
lymph nodes was noted.
A biopsy of the lesion was performed. Histopathology revealed a foreign body granulomatous reaction
with eosinophils. Fungal direct microscopy showed fungal filaments, suggesting a fungal aetiology.
Fungal culture confirmed the causative organism as Conidiobolus coronatus. Treatment was started with
oral antifungal therapy, with saturated potassium iodide initially, and then oral itraconazole in subsequent
relapses. Response for itraconazole was more dramatic compared to saturated potassium iodide. Infection
showed a remitting and relapsing course. Currently, our patient is on oral itraconazole following his third
relapse with complete resolution of lesions. Duration of treatment is yet to be decided.
Conclusion:
Even though rhinofacial conidiobolomycosis is rare in Sri Lanka it should be considered as a differential
diagnosis in patients with progressive nasal obstruction with facial disfigurement.
40
Scientific Sessions | MRI Research Day 2014
PP-12 : Genus Topomyia (Leicester 1908) sub genus Suaymyia from Sri Lanka
Ranasinghe P, Sriyakanthi Y, Premaratne NWG
Department of Entomology, Medical Research Institute, Colombo 08
Introduction:
The mosquito genus Topomyia was first discovered 104 years ago. Only one adult Topomyia mosquito
had been collected from Kalatuwawa in Colombo district by Peyton in 1975 and had been deposited in
the Natural History Museum, Washington. However, he could not confirm the identification as no
immature stages were found. During entomological investigations in Kalutara District in 2012, the
presence of an unfamiliar mosquito larva was recorded. Further identification suggested that it could
belong to genus Topomyia. The current study was design to confirm the presence of genus Topomyia in
Sri Lanka.
Objectives:
To confirm the genus Topomyia (Leicester 1908) in Sri Lanka
Methodology:
A total of 1000 leaf axils of Colocasia plants were examined in Agalawatta area. Both larvae and adults
reared from larvae were identified. Identification was done using standard taxonomic keys of
Amarasighe, FP (1995) and Rattanarithikul, R et al. (2007).
Results and discussion
About 700 leaf axils were positive for mosquito larvae of Malaya, Tripteroides, Aedes including
Topomyia. Out of 700 leaf axils examined, 40 were positive for Topomyia and were identified as
belonging to the subgenus Suaymyia. Although Peyton (1975) documented the genus Topomyia, this is
the first time that sub genus Suaymyia of the genus Topomyia has been described and identified by
researchers from Sri Lanka. This was confirmed by the Taxonomist Dr. Nagpal BN, National Institute of
Malaria Research of India.
Conclusion
Appearance of genus Topomyia (Leicester 1908), sub genus Suaymyia has been discovered and confirmed
for the first time in Sri Lanka. Further studies need to be performed to confirm the identification up to the
species level.
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PP-13 : Immunoglobulin G immune status and exposure history of measles, mumps and
varicella in post-graduate medical trainees
Jayamaha CJS, Ranpatabendi SA, Yasandi S
Department of Virology, Medical Research Institute, Colombo
Background
Medical officers are at higher risk of acquiring and transmitting infectious diseases. Knowledge regarding
immunity and vaccination history against such infections can prevent transmission.
Objectives
To determine status of immunity to measles, mumps and varicella of postgraduate medical officers and
their vaccination and past contact history
Methods
IgG serostatus of mumps, measles and varicella of post graduate medical trainees who were expected to
leave for overseas training was performed using ViroImmune (Germany) ELISA assay. Their
demographic details, speciality, past contact and vaccination history were analysed.
Results
Complete data was available only in 142 out of 191 doctors who requested immune status. Average age
was 37.9 yrs (SD± 3.49). Male:female ratio was 1:1.3. A past history of one of the diseases was available
for 98. Eighty six had obtained prophylactic vaccination (varicella =41, MMR n=82). IgG was positive in
97 (mumps), 136 (measles) and 112 (varicellas) individuals respectively. IgG was negative for one or two
diseases in 69 (48.6%) individuals. Of them, 26 had taken either MMR or varicella vaccine. Majority
(78%) of them were in clinical specialties especially in medicine, aneathesiology, paediatrics, surgery and
oncology (in descending frequency). 13 and 6 subjects who gave a past history of mumps and varicella
respectively, did not have detectable IgG levels.
Conclusions/Recommendations
A significant number of doctors in postgraduate training were not immune to mumps, measles or varicella
infections. This possesses a risk to patients and to the staff and may contribute to nosocomial
transmission. Immune status should be screened and appropriate vaccinations given, when they enter
medical practice.
42
Scientific Sessions | MRI Research Day 2014
3
Review Articles
3.1 Management of Type 2 Diabetes Mellitus
Dr. DSID De Silva MBBS, MD, MRCP, Consultant Clinical Pharmacologist
and Dr. AP Amarasingha MBBS, MSc (Toxicology)
Department of Clinical Pharmacology, Medical Research Institute
neuropathy)
Introduction
and
macrovascular
complications
(Cardiovascular, cerebrovascular and peripheral
Diabetes mellitus is a global epidemic affecting
approximately 285 million would wide, a number
that will increase to 439 million by 20301. South
artery disease). In addition to being an important
public health issue, T2 DM is a huge financial
burden on the health services.
East Asia is expected to be the region, with the
highest number of diabetic patients in the world.
Pathophysiology
Studies done in Sri Lanka show a definite upward
trend in the prevalence of diabetes mellitus (DM). A
study done in 2005 showed a prevalence of 14.7%
T2 DM is a complex endocrine and metabolic
disorder which is progressive. The interactions
between several genetic and environmental factors
among males and 13.5% among females2.
(unhealthy diet, physical inactivity and increasing
There are two forms of diabetes mellitus. Type 1
weight) result in variable degree of insulin
DM, Which is primarily due to pancreatic Beta cell
resistance and pancreatic Beta cell dysfunction3.
destruction, has an auto immune or idiopathic
Increased weight and obesity (particularly in
etiology. Type 2 DM (T2 DM) is the more common
abdominal area) are major contributions to insulin
variant and can result from either, an insulin
resistance and impaired glucose tolerance3,4. When
secretion defect or insulin insensitivity. This article
Beta cells are no longer able to secrete sufficient
will discuss only T2 DM, which accounts for the
insulin
majority of cases of diabetes.
pancreatic Beta cell function deteriorates over
Diabetes is a metabolic disorder characterized by
chronic
hyperglycaemia
with
disturbances
to
overcome
insulin
resistance,
(i.e.
time3,4) impaired glucose tolerance progresses to T2
DM.
of
carbohydrate, fat and protein metabolism. T2 DM is
Abnormalities in other hormones such as reduced
usually diagnosed in people over 40 years; however
secretion of incretin, glucagon like peptide 1 (GLP-
it is increasingly being diagnosed in younger people
1), hyperglucagonaemia and raised concentration of
including children. The prolonged exposure to
other counter regulatory hormones also contribute to
hyperglycemia associated with DM results in
insulin resistance, reduced insulin secretion, and
microvascular
hyperglycemia in T2 DM (Figure 1)5.
(retinopathy,
MRI Research Day 2014 | Scientific Sessions
nephropathy
and
43
Figure 1: Typical pathogenic features of hyperglycaemia in T2 DM
β cells
α cells
Glucagon
Secretion
Hepatic glucose
production
Insulin Secretion
Neurotransmitter
dysfunction
Hyperglycaemia
Lipolysis and
Glucose uptake
Incretin effect
Glucose uptake
44
Glucose reabsorption
Scientific Sessions | MRI Research Day 2014
Diagnosis
Table 2: Criteria for diagnosis of DM
T2 DM is characterized by a long preclinical phase
 Symptoms of diabetes plus random blood
and patients usually experience impaired fasting
glucose > 11.1 mmol/L (200 mg/dL) or
glucose (IFG) or impaired glucose tolerance (IGT),
 Fasting plasma glucose > 7.0 mmol/L (126
in the initial phase of the disease process. Early
mg/dL) or
detection requires clinical suspicion combined with
 HbA1c > 6.5%
screening of individuals.
 Two hour plasma glucose > 11.1 mmol/L (200
The
American
Diabetic
Association
(ADA)
mg/dL) during an oral glucose tolerance test
recommends screening of all individual over 45
years every 3 years and screening of individuals at
In the absence of unequivocal hyperglycemia (i.e.
an early age if they are overweight (BMI >25
the presence of classic triad of symptoms, polyuria,
2
Kg/m ) and have one additional risk factor (Table
6.
thirst and weight loss) it should be confirmed by
1) .
repeat testing.
Table 1: Risk factors for T2 DM
A fasting plasma glucose (FPG) of 5.6 - 6.9 mmol/L
 Family history of diabetes
(100-125 mg/L) is defined as Impaired Fasting
 Obesity (BMI >25 Kg/m2)
Glucose (IFG).
 Physical inactivity
Plasma glucose 7.8 – 11 mmol/L (140 – 199 mg/dL)
 Certain ethnic groups / Race
following OGTT, is termed impaired glucose
 Previously identified with IFG, IGT or HbA1C of
tolerance (IGT).
5.7 - 6.4%
 History of GDM or delivery of a baby >4 Kg
 Hypertension (BP >140/90)
 HDL cholesterol <35 mg/dL and/or triglyceride
These individuals (IGT & IFG) are at a greater risk
of progression to T2 DM and have increased risk of
cardiovascular disease.
>250 mg/dL
 Polycystic ovary syndrome or acanthosis
nigricans
 History of cardiovascular disease
Criteria for diagnosis of DM are given in Table 27 .
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Management
Table 3: Objectives of management
The main modalities in the management of
 Diagnosis
hyperglycemia are
 Relief of symptoms
1.
Life style intervention (diet/exercise)
2.
Pharmacotherapy
 Self management by patient especially
encouraging patient to monitor glycaemic control
 Dietary management / exercise / weight
reduction to a preset target range
Aims of management
These are listed in Table 3.
 Use of oral hypoglycaemics +/- insulin
 Correction & avoidance of cardiovascular risk
factors / stop smoking
Objectives may be relaxed in older patients in whom
 Regular screening for complications.
the main aim may be to avoid symptomatic
 Patient education.
hyperglycemia and drug induced hypoglycemia.
The treatment goals for adults with DM are given
in Table 46 and the essential elements in
comprehensive T2 DM care is given in Figure 26.
Table 4: Treatment Goals for adults with DM
Index
1
Goal
Glycaemic control

HbA1c
<7.0%

Pre-prandial capillary plasma glucose
3.9 - 7.2 mmol/L (70-130 mg/dL)

Peak post prandial capillary glucose
<10.0 mmol/L (<180 mg/dL)
2.
Blood Pressure
3.
Lipids
<130/80 mmHg

LDL
<2.6 mmol/L (<100 mg/dL)

HDL
>1 mmol/L (>40 mg/dL) in males
>3 mmol/L (>50 mg/dL) in females
4.
BMI
46
<25 Kg/m2
Scientific Sessions | MRI Research Day 2014
Figure 2: Essential elements in comprehensive T2 DM care
Management of T2 DM
Good glycaemic
control
 Diet / life Style
 Exercise
 Medication




Treatment of associated
condition
Dyslipidemia
Hypertension
Obesity
Coronary heart disease





Screen for / manage
complication
Retinopathy
Nephropathy
Neuropathy
Cardiovascular disease
Other
Dietary Management
Weight Loss / Exercise
Diet for people with diabetes is no different from
Lifestyle intervention in particular promotion of
that considered healthy for everyone. It is important
weight
that the diet conforms to patient’s cultural and
management of T2 DM and has shown to reduce
economic environment.
HbA1c up to 2%9. Weight loss has a positive effect
Food for people with diabetes should8
loss,
exercise
is
very
important
in
on metabolic control and cardiovascular risk factors
in T2 DM10. The patient should be advised to
 have a reduced total energy intake
maintain a healthy weight in order to maintain a
 be low in sugar
BMI of 20 – 25 Kg/M2.
 have complex carbohydrates especially foods
with low glycaemic index
 be high in fiber
 be especially low in saturated fat
Exercise improves glycaemic control even without
weight loss and result in reduced body fat content
and increases insulin response. Thirty minutes of
physical activity at least five times a week is
advisable.
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Table 5: Summary of oral therapies in T2 DM
Drug Class
Mode of Action
Sulfonylureas
 Glibenclamide
 Glimeperide
 Glicazide
 Glipizide
Enhance insulin
secretion
(secretagogue)
Biguanide
 Metformin
Inhibit
gluconeogenesis
Increase insulin
sensitivity in
muscles


Meglitinides
Repaglinide
Nateglinide
Thiazolidenediones
 Pioglitazone
Enhance insulin
secretion
(secretagogue)
Increase
sensitivity of
muscles, fat and
liver to insulin
in
Dipeptidyl peptidase - Increase
4 inhibitors (DPP -4)
endogenous
incretin
 Vidagliptin
 Sitagliptin
concentration
 Saxagliptin
 Linagliptin
α glucosidase
inhibitors
 Acarbose
48
Inhibit
carbohydrate
degradation in
gut.
Expected
HbA1c
reduction
1.0 – 2.0
1.0 – 2.0
0.5 – 1.5
0.5 – 1.0
0.5 – 0.8
0.5 – 0.8
Comments
Disadvantages
Rapidly
effective
Low cost
Long term
safety
Weight neutral
Reduction in
MI
(myocardial
infarction )
Risk UKPDS –
34 study
Rapid short
acting, Suitable
for prandial use.
Three times
daily dose
Hypoglycemia
Weight gain
Needs careful
dose titration
Low risk of
hypoglycemia
Improve lipid
profile
Contraindicated
in heart failure
Fluid retention
Weight gain
Heart failure
Fracture risk
Possible
association with
bladder CA
Long term safety
not known.
Possible
association with
pancreatitis
Weight neutral
Low risk of
hypoglycemia
Possible effect
on β cell
survival and
decline (animal
studies)
Weight neutral
Three times
daily dose
Low cost
GI side effects
Possible link to
lactic acidosis
Avoid in renal
impairment and
hypoxemia
Hypoglycemia
Weight gain
Few data for
long term safety
GI side effects
Including
diarrhoea,
flatulence and
abdominal pain
Scientific Sessions | MRI Research Day 2014
Pharmacological Management
Table 6: Incretin effects
Diet and lifestyle changes are the key to successful
 The insulin response to oral glucose is greater
treatment of T2 DM. However, due to the
progressive nature of T2 DM, the majority will
than the response to intravenous glucose.
 Cause- two intestinal peptide hormones, glucose
eventually require hypoglycemic drugs and many
dependent insulinotropic peptide (GIP) and
will require combination of hypoglycemic drugs
glucagon like peptide-1(GLP-1) have
including insulin. The choice of hypoglycemic
potentiating effect on pancreatic secretion of
drugs needs to be individualized to the patient.
insulin.
Oral Therapy
 GIP causes 30% and GLP-1 70% of incretin
effect.
1. Sulfonylureas
 Both hormones have short half lives in
2. Biguanides
circulation being degraded by dipeptidyl
3. Glinides
peptidase- 4 (DPP-4)
4. Thiazolidenediones
 The incretin effect is diminished in T2 DM
5. Dipeptidylpeptidase- 4 Inhibitors (DPP- 4
inhibitors)
Parenteral Therapies in T2 DM
6. Alpha Glucotidase inhibitors
1. GLP-1 agonists
2. Insulin
Table 5 gives a summary of oral therapies.
Table 7 gives a summary of parenteral therapies in
DPP-4 inhibitors
These agents enhance the incretin effects (Table 6)8.
T2 DM11,12. Table 8 outlines a current approach to
glucose lowering therapy13.
The enzyme DDP-4 rapidly inactivates GLP-1.
Inhibition of this enzyme potentiates endogenous
GLP-1 action.
MRI Research Day 2014 | Scientific Sessions
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Table 7: Summary of parenteral therapies in T2 DM
Drug Class
Mode of Action
GLP – 1 agonist
 Exenatide
 Liraglutide
Mimics action of
incretin hormone
GLP – 1
Expected
HbA1c
reduction
0.5 – 1.0
Insulin
 Human insulin
 Insulin analogue
 Aspart
 Lispro
 Glulisine
 Glargine
 Detemir
Mimic insulin
response
Reduce hepatic
glucose output
Increase
1.5 – 3.5
peripheral use and
reduce lipolysis
Management of Type 2 diabetes mellitus in
practice
Ideally management of patients with T2 DM should
be provided by a multidisciplinary team (physician,
endocrinologist, diabetic specialist nurse, dietician,
podiatrist)11. All patients require a comprehensive
initial assessment and a regular review. Education is
a key component in the prevention and management
of DM, in particular, self-management education
training. The aims of treatment are to reduce blood
glucose and to manage the cardiovascular risk
factors and long term complications of T2 DM14.
Lowering hyperglycemia - Evidence has shown
that intense glucose lowering reduces complications
in T2 DM15. There is controversy as to whether
intensive therapy is associated with reduced macro
vascular complications16. Measurement of HbA1c
plays a major role in management of patients with
DM since it correlates well with microvascular and
to a lesser extent, macrovascular complications7.
50
Comments
Disadvantages
Administered
subcutaneously
Weight loss
Low risk of
hypoglycemia
Possible effect on β cell
survival and decline
More sustained
glycemic improvement
compared to other drugs
1 – 4 injections daily
(analogues more
expensive)
Long term safety not
known
Possible association
with pancreatitis and
medullary carcinoma
GI side effects
Avoid in renal failure
Weight gain
Hypoglycemia
Less hypoglycemia with
analogues
Most consensus groups recommended that HbA1c
target level should be around 7%, however, it needs
to be individualized to the patient 17. HbA1c should
be tested at least twice yearly, in patients who are
meeting their target level and every 3 – 4 months in
patients whose therapy has changed or who are not
meeting their targets. For selected individuals, more
stringent HbA1c targets could be suggested,
provided that the level can be achieved without
substantial risk of hypoglycemia or other adverse
effects. These patients may include those with a
shorter duration of T2 DM, a long life expectancy
and no significant cardiovascular disease.
Conversely, higher HbA1c goals should be
considered for patients with a history of severe
hypoglycemia, a limited life expectancy, advanced
micro and macrovascular complications or extensive
co–morbid conditions. Self monitoring of blood
glucose (SMBG) is recommended for all insulin
treated patients with diabetes.
Scientific Sessions | MRI Research Day 2014
Table 8: A current approach to glucose lowering therapy
Set glycemic target
First line therapy
(In addition to lifestyle interventions)
Commence metformin if no C.I. Or commence alternative OHD authorized for monotherapy use
and suitable for individual patients
Review after 3 – 4 months - If not reaching glycaemic target, move to second line therapy
Second line therapy
(In addition to lifestyle interventions, dose optimization and advice on adherence to medication)
Add sulfonylurea or Thiazolidenediones (if hypoglycemia a concern and no heart failure)
Or DPP- 4 inhibitor (if hypoglycemia and weight gain a concern)
Or GPL–1 agonist (if hypoglycemia is a concern, weight loss desired and BMI >30 Kg/m2)
Review after 3 – 4 months - If not reaching glycaemic target move to third line therapy
Third line therapy
(In addition to lifestyle interventions, dose optimization and advice on adherence to medication)
Add or substitute with one of: thiazolidenedoines (If no heart failure) DPP-4 inhibitor (if
hypoglycemia and weight gain a concern) or GPL – 1 agonist (if hypoglycemia a concern, weight
loss desired and BMI > 30 kg/ m2) or insulin
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Macrovascular complications
pharmacological agents for smoking cessation if
Patients with DM have a two to four fold rise of
appropriate.
CVD compared to non-diabetics. Numerous
Microvascular complications
studies have shown the efficacy of controlling
These occur in many patients with DM.
individuals' cardiovascular (CV) risk factors in
preventing or slowing CVD in people with
Diabetic retinopathy - up to 40% patients have
diabetic retinopathy at the time of diagnosis.
diabetes12.
Duration of diabetes, glycaemic control and blood
Hypertension is up to three times more common in
pressure are the strongest risk factors for the
patients with diabetes than non-diabetics. The
development and progression of retinopathy20. All
recommended target for blood pressure is 130/80.
patients should have a comprehensive assessment
Dyslipidemia is common in diabetics. Lifestyle
by an ophthalmologist shortly after diagnosis and
modifications focusing on diet, weight loss and
annually thereafter.
increased
Diabetic
physical
activity
should
be
nephropathy
-
arises
from
the
recommended. Statin therapy should be added
combination of hyperglycaemia and hypertension,
regardless of baseline lipid level for diabetic
giving rise to glomerular damage, which occur up
patients with overt CVD, those without CVD who
to 40% of patients within 25 years20. Aggressive
are more than 40 years, more than one CV risk
blood pressure reduction and glycaemic control
factor and those below 40 years with poor CV risk
are of vital importance of managing diabetic
12
factor profile . Fibrates may be required for those
nephropathy21. In patients with diabetes, serum
with high triglycerides. The recommended targets
creatinine and urine albumin / creatinine ratio
for patients with T2 DM are lower than non-
should be measured at diagnosis and at least
diabetic patients; guidelines recommend a target
annually thereafter.
LDL <1.8 mmol/L or more than 50% reduction
Diabetic neuropathy - refers to a spectrum of
from baseline19.
various neurological disorders associated with
Thrombosis: Aspirin therapy has been shown to
diabetes. All patients should be screened to assess
decrease the risk of major CV events occurring in
their risk of developing foot ulcers and patients
patients with DM without CVD; however there is
should be educated on the importance of regular
a trend towards higher rates of bleeding and
foot review. The management of the neuropathy is
gastrointestinal complications. Low dose aspirin is
mainly supportive, although good glycaemic
generally recommended for patients with T2 DM
control can reduce the progression.
more than 50 years at increased CV risk
12,20
.
Summary
Lifestyle: In addition to diet and exercise, all
patients who smoke should be counseled on
smoking
52
cessation
and
treated
with
The prevalence of T2 DM is increasing in Sri
Lanka.
A
multidisciplinary
approach
to
Scientific Sessions | MRI Research Day 2014
management of diabetes which includes the patient
is recommended. Treatment of T2 DM is often
6.
7.
complicated by the progressive nature of the
disease and the need to balance target blood
glucose level against an increase risk of treatment
8.
related effects such as hypoglycemia and weight
gain. All patients require an initial assessment and
9.
regular review to ensure that they are meeting their
target HbA1c and are being monitored for CV risk
factors
and
micro
vascular
10.
complications.
Lifestyle intervention programmes to promote
11.
weight loss and increase activity levels should be
included as a part of diabetes management. Patient
compliance to treatment is often compromised by
12.
the fear of hypoglycemia and weight gain, as well
as complex therapeutic regimes. Hence, patient
education is a vital aspect of management. Most
patients require combination anti diabetic therapy
13.
14.
15.
and many will require insulin. In addition to
glucose lowering therapy, management of CV risk
factors and microvascular complications are an
16.
essential part of diabetes management.
References
17.
1.
2.
3.
4.
5.
Shaw JE, Sicree RA, Zimmet PZ, Global estimate
of the prevalence of diabetics for 2010 and 2030.
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Katulanda P, Sheriff MHR, Matthews DR, The
diabetes Epidemic in SL a growing problem. CMJ
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Stumroll M Goldstein BJ, Van Haeffen TW. Type
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Reaven GM. Role of insulin resistance in human
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Tahrani A, Bailey CJ, Delprato S, Barnett AH.
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MRI Research Day 2014 | Scientific Sessions
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Harrisons Principles of Internal Medicine, 18 th
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Kumar & Clark’s Clinical Medicine, 8th edition:
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Stratton IM, Amanda IA et al, and Association of
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Fujioka K, Benefits of moderate weight loss in
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Nathan D et al, Medical management of
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American diabetes Association, Standards of
medical care in diabetes-2011, diabetes care 2011;
34 (Suppl. 1): S 11-61.
SIGN Guidelines- Management of diabetes 2010.
NICE pathway for managing Type 2 diabetes,
downloaded from www.nice.org.uk
The ADVANCE Collaborative group, Intensive
blood glucose control and vascular outcomes in
patients with Type 2 diabetes, NEJM 2008;
358:2560-2572.
The Action to Control Cardiovascular risk in
diabetes study group, Effects of intensive glucose
lowering in type 2 diabetes, NEJM 2008; 358:
2545-59.
Sacks D et al, Guidelines and recommendations
for laboratory analysis in the diagnosis and
management of diabetes mellitus, diabetes Care
2011; 34:61-99.
The Task force for the management
of
dyslipidemias of European Society of Cardiology
(ESC) and the European Atherosclerosis Society
(EAS), ESC/EAS guidelines for the management
of dyslipidemias, European Heart Journal 2011;
32:1769-1818.
NICE Type 2 diabetes-management of Type 2
diabetes May 2009.
Vithan K, Hurel S, CME diabetes- microvascular
complications: Pathophysiology and management,
Clinical Medicine 2010; 10(5): 505-509.
53
3.2 Diagnosis of von Willebrand disease
Dr. Priyanka Herath MBBS, D. Path, MD (Haematology)
Consultant Haematologist, Department of Haematology, Medical Research Institute
Introduction
has a sensitivity of 32-100%. The prevalence of
von Willebrand Disease (VWD) is the commonest
VWD in this group was between 5-20%. So
autosomally inherited bleeding disorder, resulting in
specificity of menorrhagia as a predictor of VWD
significant bleeding symptoms in ∼1 in 1000
can be estimated as 5-20%2.
subjects, with prevalence estimates ranging from
1% to 1 in 10 0001,2. The disease shows no
geographical or ethnic predilection. Even though
both sexes inherit mutant VWF alleles with equal
frequency,
females
outnumber
males
by
approximately 2:1 in most VWD populations,
presumably because of the burden of excessive
mucocutaneous bleeding in women of reproductive
age.
most
common
presenting
symptom
is
mucocutaneous bleeding and usually bleeding is of
mild to moderate severity2, reflecting predominance
of VWD-type 1. Life threatening bleeding (CNS,
GIT)
and bleeding into unusual sites
(e.g.
haemoarthrosis) can occur in Type 3, sometimes
with
Type 2 and rarely with Type 12. Clinical
symptoms may be affected by co-existing illnesses
and medications (antiplatelet drugs can increase the
severity and oestrogen/contraceptives in females can
decrease bleeding in VWD).
Clinical evaluation of bleeding symptoms is a
challenge, because mild bleeding symptoms are
common in the healthy population1,2,3. One study
done in group a group of females with menorrhagia
had shown that menorrhagia as a predictor of VWD
54
questionnaire in patients with proven bleeding
disorders and healthy volunteers showed that the
most useful questions predicting a bleeding disorder
were related to (1) prolonged bleeding after a
haemostatic challenge; surgery/dental extraction, (2)
identification of a family member with an
established bleeding disorder2.
The evaluation of patients with mucocutaneous
Clinical evaluation of the patient
The
A study (Sramek and colleagues) using a written
bleeding should begin with a careful personal
history of excessive bleeding and family history of
bleeding. The bleeding history should identify:
duration, spontaneity, severity, sites and types of
bleeding; type of injury or insult associated, ease
with which bleeding can be stopped, history of
interventions (blood transfusions) after haemostatic
challenges (surgery, dental extractions, childbirth in
females), and concurrent medication including
herbal medication, drugs taken over the counter at
the onset of bleeding1,2,3.
In the past decade, there has been a resurgence of
interest
in
developing
assessment tools (BATs)
evaluated
1,2,3
predominantly
quantitative
bleeding
. These tools have been
in
disorders
of
mucocutaneous haemostasis, with extensive use in
studies of VWD. 1
Scientific Sessions | MRI Research Day 2014
To overcome the subjectivity of mucocutaneous
Table 1. Significant mucocutaneous bleeding
bleeding the International Society of Thrombosis
symptoms devolved by ISTH VWF SSC1
and Haemastasis (ISTH) Scientific Subcommittee
(SSC) on VWD has developed a provisional
consensus criterion on the definition of significant
mucocutaneous bleeding. According to this, if
bleeding is to be significant it requires one of the
following:1,2,3
1. At least two symptoms (Table 1) in the
absence of history of blood transfusion
2. One symptom with history of blood
transfusion
3. One symptom recurring at three distinct
occasions
1. Nose bleeding:
≥2 episodes without a
history of trauma not stopped by short
compression of 10 min or ≥1 episode
requiring blood transfusion
2. Prolonged bleeding from trivial wounds
lasting ≥ 15 min or recurring spontaneously
during the 7 days after wounding
3. Cutaneous hemorrhage and bruisability with
minimal or no apparent trauma as a
presenting symptom or requiring medical
treatment
4. Oral cavity bleeding that requires medical
attention, such as gingival bleeding or
The VWD SSC has defined positive family history
for Type-1 VWD as 1:
1. At least one first degree relative or two
bleeding with tooth eruption or bites to lips
and tongue
5. Spontaneous
gastrointestinal
bleeding
second degree relatives with history of
requiring medical attention or resulting in
significant mucocutaneous bleeding
acute or chronic anemia unexplained by
2. Having a family member with laboratory
tests compatible with Type-1 VWD
ulceration or portal hypertension
6. Heavy, prolonged or recurrent bleeding
after tooth extraction or other oral surgery
such as tonsillectomy and adenoidectomy
requiring medical attention
7. Menorrhagia resulting in acute or chronic
anemia or requiring medical treatment not
associated with structural lesions of the
uterus
8. Bleeding from other skin or mucous
membrane
surfaces
requiring
medical
treatment (eg, eye, ear, respiratory tract, or
genitourinary tract other than uterus)
MRI Research Day 2014 | Scientific Sessions
55
If the clinical history and physical examination is
specificity. The initial enthusiasm of PFA100 as a
suggestive of a bleeding disorder laboratory testing
screening tool has diminished due to low sensitivity
will be performed.
(24-41%) in patients with VWD with VWF greater
than 25%, mild platelet secretion defects and storage
Laboratory diagnosis of VWD
1)
First
line
bleeder
pool disorders, especially in the preoperative
screening
Tests:
Initial evaluation includes Full Blood Count (FBC),
Prothombin
Time
(PT),
Activated
Partial
Thromboplastin Time (APTT), and optionally
Plasma Fibrinogen or Thrombin Time (TT)1,2,5
setting1,5.
In summary, for VWD the existing primary bleeder
screening tests are of limited value. So, if the history
is strongly suggestive, specific laboratory tests for
VWD should be ordered at the first visit; von
These tests neither rules out nor rules in VWD, but
Willebrand Factor antigen level (VWF), von
will suggest whether thrombocytopenia or any
Willebrand Factor Ricof activity (VWF;RCo),
Factor deficiency might be the potential cause for
Factor VIII (FVIII)1,2,5.
bleeding.
FBC /Platelet count: is usually low in VWD-type
2B & Platelet Type-VWD (PLT-VWD) and normal
in other types.
2) Initial laboratory Tests for VWD:
In establishing the diagnosis of VWD, Type 2 and
Type 3 are usually straight forward based on the
initial tests; VWF, VWF;RCo, FVIII. Sub typing of
APTT : Often within the normal range in type 1 and
type 2A, 2B, 2M VWD. APTT shows abnormal
results only if Factor VIII is significantly reduced
which is typically significantly abnormal in Types
5
VWD-type 2 needs further tests. In contrast,
diagnosis of Type 1 VWD is often more difficult.
This is partly because not all persons with low VWF
have a molecular defect in the VWF gene1,2.
2N and Type- 3 VWD .
a) VWF:Ag level is usually measured by a
Place of Bleeding time (BT) and Platelet
Function Analyzer (PFA100):
Some centres add BT or PFA100 to their initial
laboratory tests. BT is a non-specific test with
operational variations. BT is typically prolonged in
type 3 and normal in type 2N2. It is frequently
prolonged in type 2A, 2B, 2M and can be normal in
2
type 1 .
quantitative Immune assay. Commonly based on
ELISA or Automated Latex Immune assay (LIA)
methods. The standard reference plasma is
critical and should be keyed to the World Health
Organization (WHO) standard. The results
should be reported in international units per
deciliter (IU dL-1) or as IU per milliliter (IU mL1
). Most laboratories report this as IU dL-1 as this
PFA100 is abnormal in a majority of VWD other
2,5
than 2N . For VWD and other severe platelet
is similar to the conventional way of reporting
Factor assays: a percentage of normal5.
disorders PFA100 shows 90% sensitivity and
56
Scientific Sessions | MRI Research Day 2014
ABO blood groups have a significant effect on
In type 2B VWD, acquired influences such as
plasma VWF and FVIII levels2. People with
acute stress and pregnancy cause higher level of
blood group O tend to have approximately 25%
mutant protein which result in increased in vivo
lower levels compared to the others. Although it
platelet clumping and more severe symptoms.
is recommended to stratify reference ranges for
VWF; Ag and RCo according to the blood
b) VWF:RCo; this is a functional assay of VWF
groups (Gp O and non Gp O), available limited
antigen. This test assesses the ability of VWF in
evidence shows despite ABO grouping and
the plasma to interact with GP1b of platelets to
reference ranges, the major determinant of
induce platelet agglutination in the presence of
bleeding is low VWF. So referencing VWF
the antibiotic ristocetin. (Ristocetin cofactor
results to the population reference range than to
activity-VWF:RCo).
5
ABO group is more clinically useful .
Several
methods
are
available. Methods using normal control or
formalin fixed platelet clumping or agglutination
Pre-analytical variables should be considered in
with dilutions of patient’s plasma can quantify
interpretation of VWF;Ag results.
Platelet
VWF:RCo to approximately 6-12 IU/dL2,5.
contamination of frozen plasma can lead to
ELISA assay that evaluate direct binding of
protease induced VWF structure alteration. This
VWF in plasma to platelet-GP1b in the presence
can have increased VWF;Ag and decreased
of ristocetin can measure VWF;RCo up to 1
activity1. Refrigeration of whole blood before
IU/dL and a variation of this can detect increased
separation can lead to falsely reduced VWF
VWF binding to platelets in Type 2B5. The
levels1. Certain clinical conditions can cause
newer method of binding of a monoclonal Ab to
changes in VWF (increased levels or altered
a conformational epitope of the VWF A1 loop is
multimeric structure) as an acute phase reaction1:
performed in an ELISA or LIA format and is not
surgery,
diseases,
based on ristocetin binding. Some automated
inflammatory diseases, infections, pregnancy,
methods are less sensitive and need modification
oestrogen/OCP,
of the method to detect levels < 10 IU/dL2,5.
collagen
vascular
increased
endothelial
stimulation (diffuse intravascular coagulation,
liver disease, TTP, and haemolytic uraemic
1-5
RCo activity has high intra and inter laboratory
syndrome) . Certain physiological conditions
variation1,2,5, and it does not actually measure a
like stress, anxiety, and the stage of the
physiologic function. The coefficient of variation
menstrual cycle can affect the VWF;Ag level2.
(CV) has been measured in laboratory surveys
Because of this, it is recommended in some test
are at 30% or higher especially when the activity
protocols, to quantify VWF at least twice in
is less than 12-15 IU/dL1, and this is relatively
patients with VWD to evaluate the baseline
less sensitive when VWF is <10 IU/dL. This can
value4.
potentially affect the initial diagnosis of VWD,
MRI Research Day 2014 | Scientific Sessions
57
as well as differentiation between Type 1 and
largest multimers from intermediate and small
Type
limitations
multimers and can demonstrate the changes in
VWF:RCo is wildly used and accepted as the
large multimer distribution. High resolution
2
VWD.
Despite
these
1
gold standard of the VWF activity . Results of
gels (2-3% agarose) fail to demonstrate loss of
VWF:RCo should be expressed in IU/dL based
high
on the WHO standard plasma5.
diagnostic purposes, low resolution is primarily
molecular
weight
multimers.
For
used. This is helpful to diagnose the subtypes
of type 2 and can easily identify type 3 VWD2.
c) Factor VIII assay - Lowest levels are seen in
Type 3 VWD which is 1-9 IU/dL2,5 and usually
3)
Factor VIII binding capacity: (VWF:FVIII B)
is less than 5 IU/dL1. FVIII is low in Type 2N.
evaluates the ability of patients VWF to bind
Low to normal in other VWD types2,5.
with added exogenous FVIII. Useful in
diagnosing VWD Type 2N.
3) Other Tests in defining and classifying VWD
4)
large VWF multimers to collagen. This is a
subtypes:
1)
Ristocetin
agglutination
method of assessing the functional activity of
RIPA at higher concentrations of
VWF without using ristocetin, which helps to
ristocetin (1.1-1.3 mg/mL) is absent in VWD
differentiate Type 2 from Type 1. Two recent
Type 3, reduced in Type 2A, Type 2M and
studies have shown that with type-I collagen
normal in Type 2N2,5. It is often normal in
higher values are obtained, compared to type
(RIPA):
induced
platelet
2
Type 1, Type 2B and PLT-VWD . However,
III and type IV collagen and these types show
this test is not sufficiently sensitive to reliably
significant difference in sensitivity to the loss
diagnose VWD other than Type 32,5.
of high molecular weight multimers2.
The usual ristocetin dose used in low dose
5)
VWF:RCo to VWF;Ag ratio – Although
RIPA is <0.6 mg/mL, and use of slightly
published evidence is limited, for defining the
different concentrations can be seen when
ratio of VWF:RCo/VWF:Ag to distinguish
ristocetin lot varies. Both type 2B and
VWD Type 1 from VWD Type 2 variants, it is
PLT-VWD show platelet agglutination with
recommended
low dose ristocetin, and these two types can be
laboratories clearly define a reference range
5
2)
Collagen binding capacity measures binding of
as
<0.5–0.7
until
more
differentiated by VWF: Platelet Binding assay ,
using large numbers of normal subjects and
plasma mixing studies and cryoprecipitate
VWD patients. CV for VWF:RCo can be high
challenging test.
especially when the value is low, whereas CV
VWF multimer analysis; is a qualitative assay
for the VWF:Ag is somewhat lower. Therefore,
done
electrophoresis
this ratio can be an unreliable criterion in
followed by immunostaining. Low resolution
diagnosing Type 2. It is important that same
gels (0.65% agarose gel) will differentiate
plasma standard be used in both VWF:RCo and
58
on
SDS—Agarose
Scientific Sessions | MRI Research Day 2014
VWF:Ag assays and the normal ratio and its
- No abnormality in the VWF gene has been
sensitivity
identified
has
to
be
derived
in
each
laboratories1,2,5.
in
many
individuals
who
have
mildly to moderately low VWF:RCo levels.
Laboratory criteria2,5
This recommendation does not preclude the
Current recommendation is 30 IU/dL as the "cutoff"
diagnosis of VWD in individuals with VWF:RCo of
level for supporting the definite diagnosis of VWD
30–50 IU/dL, if there is supporting clinical and/or
2,5
for the following reasons :
family evidence for VWD. This recommendation
- Blood type O is associated with "low" VWF
also does not preclude the use of agents to increase
levels;
VWF levels in those who have VWF:RCo of 30–50
- Bleeding symptoms are reported by a significant
IU/dL
and
may
be
at
risk
for
bleeding2.
proportion of normal individuals;
Condition
VWF:RCo (IU/dL) VWF:Ag (IU/dL)
FVIII
Ratio of VWF:RCo/ VWF:Ag
Type 1
<30*
<30*
↓ or Normal
>0.5–0.7
Type 2A
<30*
<30–200*†
↓ or Normal
<0.5–0.7
Type 2B
<30*
<30–200*†
↓ or Normal
Usually <0.5–0.7
Type 2M
<30*
<30–200*†
↓ or Normal
<0.5–0.7
Type 2N
30–200
30–200
↓↓
>0.5–0.7
<3
<3
↓↓↓(<10 IU/dL)
Not applicable
"Low VWF"
30–50
30–50
Normal
>0.5–0.7
Normal
50–200
50–200
Normal
>0.5–0.7
Type 3
↓
refers
to
a
decrease
in the
test
result
compared to
the
laboratory
reference
range.
* <IU/dL is designated as the level for a definitive diagnosis of VWD; there are some patients with type 1
or
†
type
2
VWD
who
have
levels
of
VWF:RCo
and/or
VWF:Ag
of
30–50
IU/dL.
The VWF: Ag in the majority of individuals with type 2A, 2B, or 2M VWD is <50 IU/dL.
MRI Research Day 2014 | Scientific Sessions
59
Type 1C VWD: It has shown that in approximately
VWF
pseudogene
on
chromosome
22.
This
15% of VWD Type 1 cases with particular
evolutionary remnant recapitulates exons 23-34 of
mutations, accelerated clearance of VWF is the
the VWF gene with 3% variance, a fact that
primary pathogenic mechanism. The VWF and
significantly complicates the genetic analysis of this
VWF propeptide (VWFpp) is synthesized in a
central region of the VWF gene4,1.
similar 1:1 ratio and an alteration in this ratio
identify increased VWF clearance. In type 1C,
Current knowledge of the molecular basis of Type 2
VWF:Ag is <30% (often <15%), with plasma VWF
and Type 3 is now well advanced, and in some
half-life <3 hrs. VWF:pp to VWF:Ag ratio is >2
instances this information is being used to enhance
(even up to >10)
and subtly abnormal VWF
clinical management. In contrast, the understanding
multimer profile may be noted. In clinical situations
of the molecular pathogenesis of Type 1 is still at an
Type 1C shows exaggerated DDAVP response (>4-
early stage, with preliminary evidence that this
fold up to 10-fold) and there is short term benefit
phenotype involves a complex interplay between
from DDAVP (2–4 hrs).
environmental factors and the influence of genetic
variability both within and outside of the VWF
Acquired VWD: This may occur spontaneously or
locus4.
associated with other disorders. Association with
following
conditions
has
been
reported:
Utility of genetic tests:
malignancies (Wilms tumour, lymphoproliferative
- In cases with diagnostic difficulty, and where the
disorders, myeloproliferative disorders- ET, plasma
specific diagnosis makes a difference in patient
cell
management. E.g; definitive diagnosis of type 2B,
dyscrasia,
paraproteinemia),
autoimmune
disorders, congenital heart disease, aortic stenosis,
PLT-VWD, Type 2N1,4.
angiodysplasia and hypothyroidism. The laboratory
- VWD 2N; Identification of type 2N with large
diagnosis
significantly from
deletions which is reported to have high risk of
congenital VWD. The evaluation should include
developing allo-antibodies with treatment and
finding the associated pathologies.
developing
does
not
differ
anaphylaxis latter1 - VWD type 3;
Prenatal diagnosis, for genetic counseling and
4. Genetic Testing:
The 175-kb VWF gene is located on the short arm
of chromosome 12 and comprises 52 exons. The
obstetric management4.
Other than above, the utility of genetic testing in
VWD is controversial1,4,2.
VWF gene sequence is replicated in part by a partial
60
Scientific Sessions | MRI Research Day 2014
VWD diagnostic strategy4
Clinical phenotype
Increasing use of quantitative bleeding assessment tools; eg, ISTH-BAT
Haemostasis laboratory • VWF:Ag
phenotype
• VWF:RCo: possibility of substituting a direct GPIb-binding assay
• VWF:CB combination of collagens I and III
• VWF:F8
• VWFpp: aids in identification of accelerated clearance variants
• VWF multimer profile
• Ristocetin-induced platelet agglutination (RIPA)
Genotype
• Type 1 VWD: premature for routine use, may be helpful in the future
• Type 2A: not usually needed
• Type 2B: helpful confirmation and rules out PT-VWD
• Type 2M: sometimes helpful
• Type 2N: definitive differentiation from mild hemophilia A
• Type 3: very helpful for genetic counseling
References:
1. Brain R Branchoford and Jorge Di Paola: Making a
diagnosis of VWD: Blood American Society of
Haematology;2012:161-167
2. W.L. Nicholas,M.B Hultin,A.H James, M.J MancoJohnson, R.R Montgomery, T.L Ortin, J.E Sadler, M.
Weinstein: Guild lines vonWillebrand: evidence
based diagnosis and management guild lines, the
National Heart, Lung,and Blood Institute(NHLBI)
Eepert
Panel
report(USA)
:
Haemophilia
:2008,14,171-232
3. Greer, John P.; Foerrster, John; Rodgers, George;
Paraskevas; Wintrobe's Clinical Hematology; 13
Editin; Congenital bleeding disorders.
4. David Lillicrap: von Willebrand disease; advances in
pathogenetic understanding, diagnosis, and therapy;
Blood American Society of Haematology; 2013
Volume 122; 254260
5. The Diagnosis evaluation and Management of von
Willebrand Disease: National Institute of Health
Department of Health and Human Services USA.gov
MRI Research Day 2014 | Scientific Sessions
6. P.D James and D Lillicrap: The molecular
characterization of von Willebrand disease;good in
parts; British Journal of Haematology ;2013
.161,166-176
7. M Frachin, M Montagnana, G Lippi ; Clinical
laboratory and therapeutic aspects of platelet-type von
Willebrand disease : Int.Jnl.Lab.Haem. 2008,30,91-94
8. Zhou Y-F, Eng ET, Zhu J, et al;. Sequence and
structure relationships within von Willebrand factor.
Blood 2012;120(2):449-458.
9. A.B Federici AB, P.M Mannucci , G. Castaman , et al
.Clinical
and
molecular
predictors
of
thrombocytopenia and risk of bleeding in patients
with von Willebrand disease type 2B: A cohort study
of 67 patients. Blood 2009;113:526-534.
10. J Evan Sadler ; Von Willebrand disease type 1: a
diagnosis in search of a disease: Blood, 2003 vol. 101
no. 6 2089-2093
61
3.3 Viral Infections in Renal Transplant Recipients
Dr. Janaki Abeynayake MBBS, Dip (Med. Micro.), MD
Consultant Virologist, Department of Virology, Medical Research Institute
This paper discusses overview of potential viral
Introduction
Viral pathogens have emerged as a significant threat
due
to immunosuppressive
transplantation1.
Renal
therapy following
transplantation
is
a
therapeutic option and has become standard therapy
2
for selected end-stage renal diseases . However, pretransplant screening of potential organ donors and
recipients, and post transplant viral monitoring may
limit the impact of these infections2.
infections in renal transplantation, screening of
recipients and donors and post transplant monitoring
for viral infections.
Sources of viral infections in the renal transplant
recipient
Sources of viral infections could be donor derived,
recipient
derived,
nosocomial
or
community
acquired. Some viral infections are commonly
Several guidelines for pre-transplant screening have
transmitted with the donor tissues and transfusion of
been
for
blood products (CMV, EBV). Some are the result of
Transplantation clinical practice guidelines on the
reactivation of latent viral infection in the host or
evaluation of renal transplant candidates, and The
from the graft in the setting of immune suppression
American Society of Transplant Physicians clinical
(HSV, VZV, adenovirus, CMV, EBV, hepatitis B
practice guidelines on the evaluation of living renal
and C) and a few are the result of community
published;
The
American
Society
3,4
exposures (influenza A and B, RSV7, 8, 9). Dual viral
transplant donors .
Pre-transplant screening of the donor and recipient
with serologic tests is an essential part to detect
active infection and past exposure to viruses, to
determine the prophylaxis and preventive strategies
infections such as CMV and human herpes virus 6
(HHV-6) or CMV and human polyomavirus BK are
also common clinical outcomes in transplant
population7, 8, 9.
after transplant, to update the vaccination status of
In addition, multiple observational studies implicate
the potential recipient and to educate the patient and
infection with HHV-6 and/or human herpes virus -7
5,6
family about preventive measures . Recommended
(HHV-7) as risk factors for CMV disease and CMV
pre-transplantation viral screening include serology
infection
for cytomegalovirus (CMV), hepatitis viruses B and
reactivation, due to infection with one virus
C, varicella zoster virus (VZV), Epstein-Barr virus
stimulating replication of other viruses in a form of
(EBV), herpes simplex virus (HSV), human
viral “cross talk”10, 11.
may
trigger
HHV-6
and
HHV-7
immunodeficiency virus (HIV) and human Tlymphotropic virus type 1 and 25.
62
Scientific Sessions | MRI Research Day 2014
infections, particularly respiratory infections, such
Timing of infections after renal transplantation
Timing of infection depends over time, mainly
determined
by
the
nature
and
severity
of
immunosuppressive regimen, from the immediate
post transplant period through months to years after
transplantation7. The pattern of infection and the
most likely pathogens can be predicted to some
extent based on this timeline, which is delineated by
3 periods: the first month after transplant, 1 to 6
months after transplant, and more than 6 months
after transplant cardiovascular1,8. This predictable
timeline of infection is also affected by numerous
factors, including newer approaches and the
changing pattern of immunosuppressive therapies,
antimicrobial
prophylaxis,
and
antimicrobial
resistance7. Furthermore, there is a possibility of
emerging newer pattern of infections during the
course of transplantation.
as influenza, constitute the greatest infectious risk1,8.
Prevention of infection
Prevention of viral infections is of the utmost
importance, and this may be accomplished through
vaccination, antiviral strategies, dietary advices and
infection control measures1. In general, vaccination
of
these
patients
is
recommended
prior
to
transplantation, though there are instances recipients
received vaccines after transplantation. The two
antiviral strategies for prevention are: antiviral
prophylaxis,
wherein
an
antiviral
drug
is
administered to all patients at risk of disease; and
pre-emptive therapy, wherein the administration of
antiviral drug, when patient develop active viral
replication before symptoms arise, which could be
guided by PCR testing8. Dietary advice, promoting
life style changes and infection control practices
However, during the early post transplant period
may help limiting of exposure to some potential
(first month), opportunistic infections are generally
pathogens.
not seen since the full effect of immunosuppression
is not present and predominantly infections are
Common viral infections in the renal transplant
recipient
associated with technical complications of surgery
and hospital-acquired infection. During the time of
Cytomegalovirus
most intensive immunosuppression from 1 to 6
CMV infection is a frequent complication in renal
months after transplantation, viral infections such as
transplant recipients12. Direct effects of CMV could
CMV, HSV, VZV, EBV, hepatitis B and C virus,
be asymptomatic, CMV syndrome and invasive end
often transmitted from tissue of seropositive donors,
organ disease. CMV syndrome can be manifested by
pose a significant risk, though HSV, CMV, VZV
fever, leucopenia, myalgia, arthralgia while invasive
infections becoming less due to novel approaches of
end
management
in
transplant
1,8
disease
may
manifest
as
organ
From
involvement such as retinitis, meningoencephalitis,
approximately 6 months to 12 months post
pneumonitis, colitis, gastritis, ulcers, hepatitis,
transplantation, the level of immunosuppression is
pancreatitis which are usually evident within 6
typically at a steady state and community-acquired
months after transplantation13. Increased risk of
MRI Research Day 2014 | Scientific Sessions
recipient .
organ
63
secondary infections (bacterial, fungal, viruses),
Nucleic acid amplification tests (NAT) have
increase risk of graft rejection and post transplant
emerged as the preferred methods for the rapid
lymphoproliferative disease (PTLD) after CMV
diagnosis and monitoring of CMV after solid organ
infection, are considered indirect effects of this
transplantation (SOT)15. NAT assays are considered
immunomodulatory virus7.
the most sensitive methods for CMV diagnosis,
During the post transplant period, CMV infection
may occurs as a primary infection or as a
reactivation8,9. Primary infection, the most severe
form of disease, occurs in a seronegative organ
recipient who receives a graft from a seropositive
donor with a latent infection13. It rarely can also
occur
through
blood transfusion and
sexual
transmission8, 9. Serologic screening for anti-CMV
IgG should be performed on both donor and
recipient before transplant to identify patients at risk
during the post transplantation period2.
The diagnosis of CMV infection is established by
the demonstration of virus in regular culture or the
demonstration of viral antigen or nucleic acid in
clinical samples14. Regular viral cultures are not
optimum tools for diagnosing CMV infection in the
post renal transplant recipient. The major drawbacks
are its low to moderate sensitivity and long
turnaround time and also positive results cannot
based on real time polymerase chain reaction
technology. As sensitivity is very high in these
technologies it has become a challenge to identify
CMV disease from asymptomatic CMV infection
and also the rate of rise in viral load is a very
important marker of CMV disease risk12,15. In
individuals with neurologic and gastrointestinal
disease, the diagnosis is frequently made with
biopsy, instead of blood, which are often negative
due to CMV disease compartmentalization15.
The main clinical utility of CMV serology in
transplantation is in the pre-transplant screening of
organ
(and
candidates
2,16
blood)
donors
and
transplant
. CMV IgM and IgG antibody testing
is not recommended to monitor the clinical course
of infection or response to treatment in post
transplant recipient because immunosuppressed
patients may or may not augment antibody with
active infection14,16.
correlate with CMV disease14. The antigen detection
Strategies for preventing CMV infection include
assay detects CMV early antigen (pp65), which is
universal prophylaxis and preemptive therapy14,16. In
present in circulating neutrophils and reflects the
universal
total viral burden15. The major disadvantages of
administered immediately after the transplant,
CMV antigenemia testing are that the interpretation
typically adopted for seronegative recipients of an
of the test is subjective and testing should be
organ from a seropositive donor16. In preemptive
processed rapidly (ideally within 6 hours) to
therapy, patients are assessed periodically with
optimize sensitivity, since test results depend on the
CMV-NAT
life span of leukocytes14.
evidence of early disease and are administered
64
prophylaxis,
after
antiviral
transplant
for
therapy
is
quantitative
Scientific Sessions | MRI Research Day 2014
antiviral therapy only in the presence of a positive
Screening is usually accomplished by quantitative
assay12, 15.
polymerase chain reaction of urine and/or plasma
for detection of BK virus21. Plasma PCR has a
Human polyomavirus BK
higher positive predictive value than urine PCR, as
Human polyomavirus BK (BKPV) associated
episodic viruria is quite frequent in this patient
nephropathy (PVAN) is well recognized as an
group, while viremia is less common and usually
important cause of progressive graft dysfunction in
precedes PVAN22. While urinary “decoy cells” have
pediatric and adult renal transplant recipients
17,18
.
high sensitivity for the detection of overt PVAN,
Data from both prospective and retrospective studies
PCR technology is four times more sensitive than
18
demonstrate that the incidence of PVAN is 1-10% .
urine
Serological evidence of past BK virus exposure has
viruria23. However, due to the focal nature of
been seen to reach 90% in adolescents and adults
PVAN, a negative biopsy result cannot rule out
around the world8,19. BK virus serology testing is
PVAN24.
cytology
for
monitoring
asymptomatic
not routinely performed prior to transplant and there
is insufficient evidence to stratify risk based on
Elimination of BK virus DNA occurs over a period
sero-status at this time17.
of 6 months with antiviral agents or a reduction in
BK virus appears to achieve latency in renal tubular
treatment
epithelial cells and active infection of renal
immunosuppression and antiviral treatment with
allografts has been associated with progressive loss
agents
of graft function ‘BK nephropathy’ in some
fluroquinolones
individuals. As a majority of patients with BK virus
immunoglobulins19,20,24. Monitoring of BK viruria or
infections
initial
viremia with PCR technology should be done with
presentation of PVAN is insidious, it is strongly
increased frequency initially, but the frequency may
recommended to screen post renal transplant
be reduced subsequently. The monitoring is done as
are
immunosuppressive therapy24. Safe and effective
asymptomatic
and
the
of
such
BKPV
as
involves
cidofovir,
reducing
leflunomide,
and
intravenous
17
patients regularly for early diagnosis . Other
a guide for antiviral and immunosuppressive
clinical presentations of BK virus are ureteral
therapy20,24.
ulceration,
stenosis
and
hemorrhagic
cystitis.
Specifically, Kidney Disease Improving Global
Outcome recommends screening for BK virus
monthly for the first 3-6 months and then every 3
months until the end of first 2 years after
transplantation and then annually until the fifth year
20
of post-transplantation .
Other viral Infections
Epstein-Barr virus
Epstein-Barr virus (EBV) contributes to the
development
post-transplantation
lymphoproliferative disease (PTLD)25. Its spectrum
ranges from benign polyclonal B cell infectious
mononucleosis
MRI Research Day 2014 | Scientific Sessions
of
like
disease
to
malignant
65
monoclonal lymphomas. The incidence of PTLD is
NAT for HBV and HCV may be indicated since
1–5% in kidney transplants cases25. The risk of
antibody seroconversion may not have occurred
PTLD is increased when an EBV seronegative
with recent exposure2. Evaluation of the donor for
patient receives a transplant graft from an EBV
hepatitis B infection includes testing for HBsAg,
26
seropositive donor . The majority of symptomatic
HBeAg, anti-HBc and anti-HBs2. Although kidneys
infections in renal transplant recipients are likely
from isolated anti-HBc positive donors carry a low
related to reactivation of donor virus thus, pre
risk of transmission to renal transplant recipients, a
transplant serological screening, both donor and
donor with isolated anti-HBc positive serology
recipient is essential and recommended to identify
should be further tested to differentiate acute
patients at risk before transplantation26,27.
infection or remote exposure. On the other hand,
Diagnosis and monitoring of EBV infection or
PTLD relies on quantitative EBV PCR (viral load)
testing26. The American Society of Transplantation
recommends monitoring EBV viral load monthly for
one year in EBV seronegative recipients with
seropositive
donors
following
solid
organ
transplantation5. Rising EBV viral titers should raise
the suspicion for EBV related PTLD25.
organs from HBsAg positive donors can be used in
anti-HBc positive/anti-HBs positive recipients while
requiring lamivudine prophylaxis for one year28.
Kidneys from HBsAg positive donors have a higher
risk of transmitting HBV infection to their recipients
and the risk of transmission is greater if the donor
status is HBsAg positive along with HBeAg
positivity28. Both donor and recipient should be
tested for the presence of hepatitis C infection
Reduction of immunosuppression has been a
(hepatitis C antibody) with standard serologic
mainstay in the therapeutic approach of PTLD27.
testing prior to renal transplantation2,29. Hepatitis B
Antiviral therapy can be useful in reducing viral
PCR testing reveals plasma viral load and is most
load and counteracting the immunosuppressant
useful for post transplant monitoring purpose, if
effect of the virus25,26. Another treatment option, the
kidneys are harvested from HBsAg positive
anti-CD20 monoclonal antibody, rituximab, has
donors29.
shown promising results in treating PTLD27.
Hepatitis B vaccination is recommended for all
Hepatitis viruses B and C
susceptible
Viral hepatitis in renal transplant recipients is
recommended for pre-end-stage renal disease
usually caused by hepatitis B or hepatitis C virus8,9.
patients before they become dialysis dependent.
Currently, the prevalence of hepatitis B virus
Patients with uraemia who were vaccinated before
infection among patients on renal transplant is
they required dialysis have been shown to have
estimated to about 0.1- 0.4%28.
higher antibody titers. For patients undergoing
Pre-transplant evaluation is recommended in both
donor and recipient2. Repeat serologic testing and
chronic
dialysis
patients
and
is
haemodialysis, higher vaccine dosages or an
increased number of doses are recommended.
Testing after vaccination is recommended for
66
Scientific Sessions | MRI Research Day 2014
haemodialysis patients to determine their response
Ninety percent of adult solid-organ transplant
to the vaccine. Annual testing for hepatitis B surface
recipients are VZV seropositive; reactivation in this
antibody (anti-HBs) should be done to assess the
group will cause herpes zoster8. The remaining 10%
need for a booster dose. A booster dose should be
are VZV seronegative and are at risk of primary
administered when anti-HBs levels decline to <10
infection8. The incidence of VZV in renal transplant
mIU/mL29.
recipients is approximately 4-12%8. In a study of
434 renal transplant recipients, 7.4% had herpes
Herpes simplex viruses
zoster with a median time to onset of 9 month32. The
The incidence of herpes simplex viruses (HSV) in
main complications of a VZV infection in this
renal transplant recipient is estimated to be
immunosuppressed population were disseminated
approximately
8
53% .
Most
herpes
simplex
infections in renal transplant recipients occur
intravascular coagulation (DIC) and hepatitis in
almost half and pneumonitis in 29% of patients33.
because of reactivation of the virus8. HSV is the
most common form of encephalitis in transplants
recipients, and diffuse interstitial pneumonitis may
complicate disseminated disease7,30. In the absence
of prophylaxis, HSV may be seen early, in the first
post-transplant month due to reactivation or primary
Pre-transplant screening of patients for VZV
infection should be performed and seronegative
patients
should
transplantation
be
vaccinated
before
organ
2,31
. However, due to the fact that the
VZV vaccine is a live vaccine, the vaccine should
not be given if transplantation is expected within
HSV infection31.
four to six weeks, to prevent active viral shedding at
Diagnosis of HSV may be made with the aid of
the time of transplantation31. Post-transplant VZV
HSV PCR technology from cerebrospinal fluid
diagnosis can be established with clinical samples;
(CSF), bronco-alveolar lavage, plasma, vesicular
CSF, plasma, bronco-alveolar lavage and vesicle
lesions or visceral tissue samples31. Due to high
contents using PCR technology1, 33.
seroprevalence in the adult population, post
transplant serology is rarely helpful in the setting of
A VZV naive transplant patient who is exposed to
someone infected with varicella should receive
active infection5,8.
varicella immune globulin (VZIG) within 96 hours
Oral or IV antivirals including acyclovir and
of exposure1,31. If VZIG is not available or the
foscarnet are effective therapy. The risk of herpes
patient presents after 96 hours following exposure,
simplex
acyclovir may be considered for post exposure
virus
after
transplantation
can
be
significantly reduced with the use of acyclovir
prophylaxis31.
prophylaxis31.
Respiratory viruses
Varicella zoster virus
The most common respiratory viruses include
Varicella zoster virus (VZV) infection causes two
influenza A and B, parainfluenza, metapneumo
distinct clinical diseases following transplantation.
MRI Research Day 2014 | Scientific Sessions
67
viruses, respiratory syncytial virus and adeno
viruses. In general, these viruses are the frequent
cause
of
community
acquired
infections
in
transplants recipients. They tend to have a more
prolonged and complicated course, with higher rates
of pneumonia leading to bacterial and fungal superinfections. A majority of community acquired
infections may present several months after
transplantation. Early viral infections are usually
Adenovirus
Adenoviruses (AdV) are emerging pathogens with a
prevalence of 11% viruria and 6.5% viraemia in
kidney transplant recipients35. Although AdV
infection is common, interstitial nephritis (ADVIN)
is rare with only 13 biopsy proven cases reported in
the literature35. Adenovirus can be diagnosed with
AdV-DNA PCR technology in the presence of
clinical symptoms36.
caused by opportunistic viruses (CMV, HSV 1 & 2,
VZV, HHV-7) or as nosocomial infections. During
Human immunodeficiency virus
epidemic periods of influenza, post transplant
Human immunodeficiency virus (HIV) seropositive
populations experience relatively high frequency of
donors have not been utilized in transplantation, due
8
infection following person-to-person contact .
to the known risk of transmission to the recipient6.
Influenza prophylaxis should be administered as
HIV-1 and 2 serology are required for all potential
post-exposure prophylaxis to transplant recipients in
donors and at least HIV-1 serology on all
circumstances such as influenza epidemics and
recipients2. In the potential living donor with risk
nosocomial outbreaks, in addition to inactivated
factors for HIV exposure but negative HIV
influenza vaccination on an annual basis. Influenza
serology, a molecular viral test should be obtained,
vaccine is recommended in the first six months after
as these tests become positive prior to the
transplantation, though live attenuated influenza
development of a positive antibody test1, 2.
vaccine should not be given to this population1,34.
Human herpesvirus-6
Diagnosis of influenza in clinical sample can be
done using sensitive assays like RT-PCR34. All post
transplant patients should be investigated with the
first symptoms of respiratory infections. If they are
Human herpesvirus-6 (HHV-6) infections have been
reported in kidney transplant recipients, possibly
due to reactivation of recipient’s endogenous virus,
and the incidence is estimated to be 23–55%37.
positive for Influenza A or B, RSV or parainfluenza type 3, isolation and other respiratory
Post transplant HHV-6 viral load monitoring has
infection control practices need to be practiced.
been suggested as it is associated with CMV disease
They
other
and a higher rate of acute and chronic graft rejection
immunocompromised patients until they are proved
has been reported in both adult and pediatric
to be negative by two PCRs of nasal and throat
transplant recipient37. Generally, HHV-6 has been
swabs.
associated with fever, rash; encephalitis, hepatitis,
cannot
be
managed
with
the
myelosuppression and interstitial pneumonitis in the
transplant population.
68
Scientific Sessions | MRI Research Day 2014
Currently, molecular assays, both qualitative and
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Scientific Sessions | MRI Research Day 2014
4
Research Projects of Medical Research Institute 2012-2013
Bacteriology
A multi centre laboratory study of gram negative
bacterial blood stream infections in Sri Lanka
Chandrasiri P., Elwitigala J.P., Nanayakkara G.,
Chandrasiri S., Patabendige G., Karunanayake L.,
Perera J., Somaratne P., Jayathilleke K. (2013) In
Ceylon Medical Journal 58:3: 56-61
Outbreak of leptospirosis after white-water
rafting: sign of a shift from rural to recreational
leptospirosis
in
Sri
Lanka?
Agampodi
SB, Karunarathna D, Jayathilala N, Rathnayaka
H, Agampodi
TC, Karunanayake
L.
(2013)
Epidemiology and Infection 2013 June, 26: 1-4
Mupirocin resistance among isolates of methicillinresistant Staphylococcus aureus at National
Hospital Sri Lanka. Samaranayake W.A.M.P,
Karunanayake L, Patabendige G. Accepted for oral
presentation at Annual academic sessions, Sri Lanka
College of Microbiologists August, 2014
High serum lipid peroxide and low anti-oxidant
capacity in leptospirosis. Narmada Fernando,
Niloofa, Sachith Maduranga, Lilani Karunanayake,
Janaka De Silva, Senaka Rajapakse, Sunil
Premawansa and Shiroma Handunnetti. Accepted for
oral presentation at One Health International
Conference-2014
Wolttan T, De Silva NL, Rodrigo C, Karunanayake L,
Wickremesinghe H,De Silva HJ, , Premawansa S,
Rajapakse S, Handunnetti SM. In Proceedings of The
Annual Research Symposium, University of Colombo
2013 page 178
Laboratory
confirmation
of
Leptospirosis:
Comparison between microscopic agglutination
test and IgM rapid test Leptocheck WB Niloofa
MJR, Fernando GTG, Fernando TRGN, Wolttan T,
De Silva NL, Rodrigo C, , Wickremesinghe H,
Premawansa G, Karunanayake L, Wickremesinghe
AR, De Silva HJ, Premawansa S, Rajapakse S,
Handunnetti SM. Abstract in Proceedings of the 6th
Annual scientific sessions of Institute of Biochemistry,
Molecular Biology and Biotechnology, University of
Colombo, 2013, Abstract no.13, pg 21.
Low serum nitrite level and anti-oxidant capacity
in severe leptospirosis in Sri Lanka. Fernando
TRGN, Niloofa MJR, Fernando GTG, De Silva NL,
Rodrigo C, Karunanayake L, Wickremesinghe H,
Dikmadugoda N, Premawansa G, De Silva HJ,
Rajapakse S, Premawansa S, Handunnetti SM.
Abstract in Proceedings of the 6th Annual scientific
sessions of Institute of Biochemistry, Molecular
Biology and Biotechnology, University of Colombo,
2013, Abstract no.14, pg 22.
Increased oxidative stress in severe leptospirosis
Fernando TRGN, Niloofa MJR , De Silva NL,
Fernando GTG, Wijerathne PPB, Rodrigo C,
Wickremesinghe H, Dikmadugoda N, Premawansa
G, Karunanayake L, De Silva H J, Rajapakse S,
Premawansa S, Handunnetti S M. Oral presentation
at Annual Research Symposium, University of
Colombo 2013.
Low serum anti-oxidant capacity in severe
leptospirosis patients in Sri Lanka. Fernando
TRGN, Niloofa MJR, Fernando GTG, De Silva NL,
Rodrigo C, Karunanayake L, Wickremesinghe H,
Dikmadugoda N, Premawansa G, Wickremesinghe
AR, De Silva HJ, Rajapakse S, Premawansa S,
Handunetti SM. Abstract in Proceedings of the 33rd
Annual sessions of the Institute of Biology, 2013: pg
65.
Laboraotry
confirmation
of
Leptospirosis:
Comparison between microscopic agglutination
test IgM ELISA and IgM rapid test Leptocheck
WB Niloofa MJR, Fernando GTG, Fernando TRGN,
Rapid detection of severe leptospirosis using a
simple cost-effective method, Fernando TRGN,
Handunetti SM, Niloofa MJR, Fernando GTG, De
Silva NL, Wijerathne PPB, Rodrigo C, Karunanayake
MRI Research Day 2014 | Scientific Sessions
71
L, Wickremesinghe H, Dikmadugoda N, Premawansa
G, De Silva HJ, Wickremesinghe AR, Premawansa S,
Rajapakse S. (Oral presentation) Abstract in
Proceedings of the 46th Annual academic sessions of
the Ceylon College of Physicians, 2013: pg 53.
Determination of serum lipid peroxide and NOx
level in severe leptospirosis patients in Sri Lanka.
Wolttan T, Fernando GTG, Niloofa MJR, Rodrigo C,
Wickremesinghe H, Dikmadugoda N, Karunanayake
L, De Silva HJ, Premawansa S, Rajapakse S,
Handunetti SM. Abstract in Proceedings of the 6th
Annual scientific sessions of Institute of Biochemistry,
Molecular Biology and Biotechnology, University of
Colombo, 2013, Abstract no.15, pg 24.
Peters D (2012) In MRI Research Day 2012, Abstract
and Programme book: page 45 – First Place poster
presentation, MRI Research Day 2012
Isolation of Bibersteinia trehalosi from a patient
with septicemia following a dog bite Karunanayake
L, Wijesekara H, Udangawa R, Peters D (2012) In
MRI Research Day 2012, Abstract and Programme
book: Page 46
A
Preliminary
Study
on
Serological
Characterization of Human Leptospirosis in Sri
Lanka Karunanayake L, Perera R, Gunaratne N,
Samaranayake A (2012) In MRI Research Day 2012,
Abstract and Programme book, page 47
Change of haematological parameters in
leptospirosis. De Silva NL, Fernando TRGN, Niloofa
MJR, Fernando GTG, Rodrigo C, Karunanayake L,
De Silva HJ, Premawansa S, Handunetti SM,
Rajapakse S. Abstract in Proceedings of the 46th
Annual academic sessions of the Ceylon College of
Physicians, 2013, Abstract no. PP5, pg 58.
Diagnosis of Leptospirosis: Confirmed vs probable
cases of leptospirosis and the importance of testing
paired serum samples Niloofa MJR, Fernando GTG,
ThevarajahW1, Rodrigo C, Karunanayake L, De
Silva HJ, Premawansa S, Rajapakse S, Handunetti
SM.(2012) In, MRI Research Day 2012 Abstract and
Programme book page: 21
Outbreak of blood stream infection with Extended
spectrum betalactamases producing Enterobacter
cloacae in a neonatal unit at a tertiary care hospital
in Sri Lanka Karunanayake L, Abeykoon M,
Senanayake N. Abstract in ISAAR 2013, 9th
International symposium on antimicrobial agents and
Resistance Malaysia, symposia and poster abstracts
2013: p 58
An evaluation of the performance of clinical
bacteriology laboratories in Sri Lanka Kulatunga
KAKC, Rajapakshe RRN, Rangama BNLD, Pavithra
DMN, Karunanayake L (2012) In, Abstract and
Programme book, MRI Research Day 2012 page: 49
Outbreak of blood stream infection with Extended
spectrum betalactamases producing Klebsiella
pneumoniae in a neonatal unit at a tertiary care
hospital in Sri Lanka Senanayake N., Karunanayake
L. Abstract in ISAAR 2013, 9th International
symposium on antimicrobial agents and Resistance
Malaysia, symposia and poster abstracts 2013: p 90
Emergence of carbapenemase-producing Klebsiella
pneumoniae ssp. pneumoniae from clinical isolates
Karunanayake L, Gunawardana N, Wijesooriya V,
72
Enteric, Anaerobic, Food and water Microbiology
and Serology Laboratory
Contamination status of well water with special
emphasis
of
some physico-chemical
and
microbiological parameters at selected five GN
divisions in Maharagama Pathmalal M Manage, S.
Pathirage. Presented at International conference on
public health Innovation NIHS Kalutara May 2013.
Abstract journal on International conference on
public health Innovation
Salmonella serotypes isolated or serotyped at the
National Reference enteric laboratory and their
antibiotic sensitivity pattern 2013 Pathirage SP,
Wijegunawardana N, Jayamaha C, Kastriarachchi K.
Accepted for annual academic session SLCM 2014
Scientific Sessions | MRI Research Day 2014
Salmonella serotype Paratyphi A with an unusual
biochemical pattern Wickramasinghe D, Pathirage
S, Vidanagama D, Corea E. Accepted as a poster for
annual academic session SLCM 2014
Chemical and E coli contamination status of
surface
water
in
Kelani
river
basin.
M.G.Y.L.Mahagamage, S.D.M.Chinthaka, M.V.S.C.
Pathirage, Pathmalal M Manag. Accepted to be
presented as an oral presentation and International
conference on multidisciplinary approaches (ICMA
2014) At University of Sri Jayawardanapura August
2014.
Determination of acute mammalian toxicity in
yellow rain water collected after colored rain in
different areas in Sri Lanka. Samaranayake, A.,
Thammitiyagodage, M.G., Pathirage, M.V.S.C,
Kumara,W.G.S.S., Karunakaran, R. Accepted for oral
presentation in Wayamba International conference,
2014.
Deshpande Jagadish, Anna – Lea Kahn , Roland W
Sutter. Vaccine 2012, 30(52):7561–7565.
Food Dependent exercise induced anaphylaxis –
Wijesekera D, de Silva R, Gunewardena S et al. Oral
Presentation C2 Allergy and Immunology Society of
Sri Lanka Biennial sessions 2012
Pregnancy outcomes of a cohort of Sri Lankan
women
with
anti-phospholipid
syndrome.
Wijeyaratne CN, Jayawardena DBIA, Galappaththi
SLA, Palipane E, Gooneratne L, Seneviratne SL,
Ratnayake D. de Silva R. C6 Allergy and Immunology
Society of Sri Lanka Biennial sessions 2012 Won first
prize
Vaccine derived poliovirus (VDPV) isolated from a
child with severe combined immunodeficiency
(SCID) – first in Sri Lanka. C7 Gunasena S, de Silva
R et al. C7 Allergy and Immunology Society of Sri
Lanka Biennial sessions 2012
The prevalence of KPC gene and associated factors
in elevated carbapenem resistant Klebsiella
pneumoniae strains in selected hospitals in the
Colombo District. Suranadee Y.W.S, Perera J,
Pathirage M.V.S.C, Gamage S. Accepted for academic
sessions SLCM 2014
Randomized double control control clinical trial of
efficacy and safety of low dose rituximab compared
to leflunamide in patients with refractory
rheumatoid arthritis. Wijesinghe H, Ooshagowry S,
Galappaththy S, de Silva R et al. O22. SLMA sessions
2011 Won 2nd Prize
Histopathology
Effect of dietary supplementation with coconut
milk and soya milk on the lipid profiles of normal
free living Sri Lankan subjects Ekanayaka RAI,
Ekanayaka NK, De Silva PGSM, Perera B, Senadeera
SPD. In, Abstract and Programme book, MRI
Research Day 2012 page: 23
Autosomal recessive hyper IgM (AR HIGM) due to
CD 40 deficiency presenting with recurrent
infections and abnormal gait. Mahboobeh
Mahdavinia, de Silva R et al . Clinical Immunology
Society meeting 2012 Chicago USA
Prevalence of resistance to antiplatelet agents in
patients with coronary heart disease in Sri Lanka
Ekanayaka RAI, Ekanayaka NK, Pusparajah T, De
Silva PGSM, Nazliya N, Senadeera SPD, Herath
HMJP, Waniganayake Y. In, Abstract and Programme
book, MRI Research Day 2012 page: 24
Immunology
Prevalence of prolonged and chronic poliovirus
excretion among persons with primary immune
deficiency disorders in Sri Lanka. Rajiva de Silva,
Sunethra
Gunasena,
Sepali
Gunawardena,
Damayanthi Ratnayake, GD Wickremesinghe ,
MRI Research Day 2014 | Scientific Sessions
Diagnosis of specific antibody deficiency in
children with recurrent infections. Niloofa MJR,
Munasinghe TMJ, Senanayake MP, de Silva NR C5
Allergy and Immunology Society of Sri Lanka Biennial
sessions 2012
Investigation of immunological parameters in
patients with rheumatoid arthritis receiving low
dose rituximab or leflunamide. Wijesinghe H, de
Silva R et al. Poster 46 SLMA sessions 2011
Food Dependent exercise induced anaphylaxis –
Wijesekera D, de Silva R, Gunewardena S et al. Oral
Presentation
73
Laboratory Animal Centre
Impact of the composition of selected dug well
water from North Central Province (NCP) in the
development of interstitial nephritis, hepatocellular
carcinoma and hepatitis in Wistar rats.
Thammitiyagodage, M.G. , Gunatillaka, M.M. ,
Ekanayaka, N., Rathnayake, C., Horadagoda, N.U.,
Jayatissa, R., Kumara, W.G.S.S., Gunaratne, U.K.S.C.
MRI research day 2012- awarded 2nd prize for oral
presentations.
Preliminary study of the Prevalence of
Leptospirosis in Domestic Dogs in Suburbs of
Colombo, Sri Lanka. Thammitiyagodage, M.G. ,
Somaratne, P., Perera, K.C.R and Roshan Priyantha.
65thAnnual convention of Sri Lanka Veterinary
Association 2013.
Expression, sub cellular localization and tissue
localization of a novel parasitic nematode-specific
protein from bovine filarial parasite Setaria
digitata. Rodrigo, W. W. P. , Dassanayake, R. S. and
Thammitiyagodage,
M.
G.
(2013).
SLAAS
Proceedings of the 69th Annual Session. 14
Proanthocyanidins in inflorescence of Cocos
nucifera L, an ayurvedic drug used in
gynaecological
disorders.
Padumadasa,
C.,
Dharmadana, H. D. K., Abeysekera, A .M and
Thammitiyagodage, M. (2013). Poster presentationSLAAS Proceedings of the 69th Annual Session, 2013.
Detection procedure for Papaya phytoplasam.
Annals of Sri Lanka. Ranasinghe, C., Dissanayaka,
S., Thammitiyagodage, M., Ekanayaka, R. Department
of Agriculture, 2013 (15) 293-297
Contribution of the Medical Research Institute
(MRI) in the Development of Laboratory Animal
Science Field in Sri Lanka. Thammitiyagodage,
M.G., Jayasekera, S., Karunakaran, R.Inaugural
Scientific Conference of Sri Lanka Association For
Laboratory Animal Science, 2014.
Animal Centre at the Medical Research Institute of
Sri Lanka. Thammitiyagodage, M.G. Animal Lab
News (ALN) world magazine, USA, 2014 (7) pp16-17
Determination of acute mammalian toxicity in
yellow rain water collected after colored rain in
different areas in Sri Lanka. Samaranayake, A. ,
Thammitiyagodage, M.G., Pathirage, M.V.S.C.,
Kumara,W.G.S.S., Karunakaran, R. Accepted for an
oral presentation in Wayamba International
conference, 2014.
Molecular Biology
First report of Listeria monocytogenes serotypes
detected from milk and milk products in Sri
Lanka. Wijendra, W.A.S, Kulatunga,K.A.K.C., and
Ramesh, R. (2013) Eighteenth International
Symposium on Problems of Listeriosis (ISOPOL
XVIII-Goa,India) Sep_19-22_2013.
Early and rapid detection of Dengue and
Chikengunya viruses in fever patients by reverse
transcription polymerase chain reaction (RT-PCR)
during the recent epidemics 2008-2009 in Srilanka.
Kuruppuarachchi, K. G. R., Perera,MGAN.,
Gunasena,S., Ramesh,R. Interational Conference on
Public Health Innovations held at the NIHS,Srilanka
from 2nd-4th May 2013
First Report of Listeria Monocytogenes Serotypes
Detected From Milk and Milk Products in Sri
Lanka Wijendra, W.A.S, Kulatunga,K.A.K.C., and
Ramesh, R. Advances in Veterinary and Animal
Sciences special issue 5.30 Sept. 2014 (Accepted,
appropriate date of publication)
Mycology
The burden of serious fungal infections in Sri
Lanka. Primali I. Jayasekera, David W. Denning,
P.D.
Perera,
Amitha
Fernando,
Sadara
Kudavidanage. Poster presentation at 5th Congress of
Asia Pacific Society for Medical Mycology APSMM
2013, 19-20th June Chengdu, China
The burden of serious fungal infections in Sri
Lanka. Primali I. Jayasekera, David W. Denning,
74
Scientific Sessions | MRI Research Day 2014
P.D.
Perera,
Amitha
Fernando,
Sadara
Kudavidanage. Poster presentation at 6th Trends in
Medical
Mycology,
11-14th
October
2013
Copenhagen, Denmark
Rhinocerebral Mucormycosis : A case report
Gunasekera GCS, Patabendige CGUA, Jayasekera
PI, Dayasena RP (2014) Accepted as a poster
presentation for MRI Scientific Sessions 2014
A ten year retrospective study to evaluate the
fungal pathogens isolated from skin, hair & nail
samples received at Department of Mycology,
Medical Research Institute. Jayasekera Primali I,
Kudavidanage Sadara,
Perera P. D. Poster
presentation at the 2nd Annual Conference and
Scientific Sessions of Sri Lankan Society for
Microbiology (SSM) – 2013
Antifungal activity of punica granatum against
dandruff causing fungi Perera DFTN, Wijendra
WAS and Fernando KMEP (2014) Accepted as an
poster presentation for MRI Scientific Sessions 2014
Identification of fungi in bat guano in Peradeniya,
Sri Lanka. Kudagammana HDWS, Thevanesam V,
Wijedasa MH, Jayasekera PI. Oral presentation at the
2nd Annual Conference and Scientific Sessions of Sri
Lankan Society for Microbiology (SSM) – 2013
In vitro study to determine the antifungal activity
of selected medicinal plants against fungi causing
superficial skin infections Perera DFTN, Fernando
KMEP and Wijendra WAS (2013) Second Annual
Conference and Scientific Sessions of Sri Lankan
society for Microbiology (SSM)
Antifungal activity of punica granatum against
dandruff causing fungi Perera DFTN, Wijendra
WAS and Fernando KMEP (2013) Jaffna Medical
Association Conference (JMA) 2013
First isolation of Cryptococcus neoformans from
sputum in Sri Lanka - presented as nonresponding
pneumonia – case presentation Wickramasinghe D,
Bowattage S, Jayasekera PI, Dhammika RAHM,
Wijesundara WMSK, Malkanthi MA (2014) Accepted
as a poster presentation for MRI Scientific Sessions
2014
Fungal keratitis - Sri Lankan picture Jayasekera
Primali I., Kudavidanage Sadara, Perera P. D (2014)
Accepted as a poster presentation at the Annual
Academic Sessions of Sri Lanka College of
Microbiologists 2014
“Chronic rhinofacial conidiobolomycosis – A case
report from Sri Lanka” –case presentation De Mel
Premalal, Perera LSJ, Fernando WSD, Jayasekera
PI, Perera PD, Malkanthi MA (2014) Accepted as a
poster presentation for MRI Scientific Sessions 2014
MRI Research Day 2014 | Scientific Sessions
Natural Products Chemistry
Screening of medicinal plants for antifungal
activity Perera, D.F.T.N., Fernando, K.M.E.P.,
Perera, P., Wijendra ,W.A.S. Submitted for MRI
Scientific Sessions
Investigation of antibacterial properties of
endophytic fungi isolated from Neoclitsea cassica
Fernando,T.M.M., de Silva E.D., Wijayarathna,C.D.,
Senadeera.S.P.D., de Silva P.G.S.M., Nicholas I.H.V.
Presented at the International Conference on
Pharmaceutical Science and Chemical Technology,
Colombo 16/12/2013
Investigation of antibacterial properties of
endophytic fungi isolated from Artocarpus nobilis
Dissanayaka G, de Silva E.D., Wijayarathna, C.D.,
Senadeera S.P.D., de Silva P.G.S.M., Nicholas,I.H.V.
Isolation and antimicrobial activity evaluation of
secondary metabolites of Walidda antidysentrica
Perera M.G.A.N., Anuradha N.G.D., Senadeera
S.P.D. Submitted for MRI Scientific Sessions
Nutrition
National Nutrition and Micronutrient Survey 2012
among Children aged 6-59 months
Weight Reduction Intervention Study – Completed
in March 2014
Parasitology
Detection of Microfilaria in peripheral blood
Smears
using
Image
Analysis.
Sudaraka
Mallawaarachchi, G.V.A. Premalal, K.W.S.S.
Wimalana, A.S. Liyanage, Sagarika Samarasinghe,
75
Nuwan D. Nanayakkara, Proceedngs of the 8th
International conference on Industrial and Intelligent
Systems, IEEE. Peradeniya, Sri Lanka
A case of Hymenolepis diminuta (rat tape worm)
infestation in a child. Ceylon Medical Journal. 2014;
59, no.2:pp 70-71
Molecular evidence of hantavirus infection among
clinically suspected patients with haemarrhagic
fever with renal syndrome (HFRS) Muthugala
MARV, Manamperi AAPS, Gunasena S, Hapugoda
MD, Goran Butch - 22nd Annual Scientific Sessions of
the Sri Lanka College of Microbiologists 2013 (First
Prize)
Rabies & Vaccine Quality Control
Molecular epidemiology of human rabies virus in
Sri
Lanka.
Matsumoto
T,
Ahmed
K,
Karunanayake D, Wimalaratne O, Nanayakkara S,
Perera D, Kobayashi Y, Nishizono A. Infection,
Genetics
and
Evolution
2013;18:160-167.
http://dx.doi.org/10.1016/j.meegid.2013.05.018
Development of recombinant protein antigen using
bacterial expression system for the detection
Of anti-chikungunya (CHIK) antibodies
Athapaththu AMMH, Khanna N, Inouve S, Gunasena
S, Abeywickrama W, Hapugoda M - 22nd Annual
Scientific Sessions of the Sri Lanka College of
Microbiologists 2013 (Second Prize)
Pattern of immunogenicity in a representative
group
of
canines
following
anti-rabies
immunization.
Mangala
Gunatilake,
Ruvini
Pimburage,
Omala
Wimalaratne,
Aindralal
Balasuriya, Devika Perera. Proceedings of the 37th
International Union of Physiological Sciences
Congress held in Birmingham, UK in 2013; PCA293
(Electronic publication only)
http://www.physoc.org/proceedings/abstract/Proc%20
37th%20IUPSPCA293
Development of recombinant protein antigen using
yeast expression system for the detection of
anti-chikungunya (CHIK) antibodies in clinical
samples Athapaththu AMMH, Khanna N, Inouve S,
Gunasena S, Abeywickrama W, Hapugoda M 69th Annual Scientific sessions of the Sri Lanka
Association for the Advancement of Science 2013
Immunogenicity study following reduced dose (4
doses) intradermal vaccination for anti-rabies post
exposure therapy. Herath H M A K, Wimalaratne O,
Perera K A D N. Poster presentation at 22nd Annual
Academic Sessions of the Sri Lanka College of
Microbiologist 2013.
Virology
Incidence of congenital rubella syndrome /
congenital rubella infection and characterization of
rubella virus from samples presented to MRI.
Jayamaha J, Wijeratne TD, Withanage WNL,
Fernando KBR, Wickramasinghe G, Galagoda G. 22nd Annual Scientific Sessions, Sri Lanka College of
Microbiologists. 25-26th July 2013
Early and rapid detection of dengue and
chikungunya viruses in fever patients by reverse
transcription polymerase reaction (RT-PCR)
during the recent epidemics 2008 - 2009 in Sri
Lanka Kuruppuarachchi KGR, Perera MGAN,
Gunasena S, Ramesh R - International conference on
Public Health Innovations 2013
76
Epidemics in developing countries: Need for a
dengue vaccine Sunethra Gunasena - Symposium on
Modernization of vaccine productions and platforms:
Impact on global health - American association of
Pharmaceutical Scientists Annual meeting and
Exposition November 2013
Chikungunya: Vector borne diseases in Sri Lanka,
current burden, trends, determinants, challenges
in diagnosis, clinical management and control
Sunethra Gunasena - World Health Day
Collaborative activity of SLMA, WHO and Ministry of
Health 3rd April 2014
Guidelines on Management of DF & DHF in adults
Sunethra Gunasena - Member of the Guidelines
Development Committee, National Guidelines,
Ministry of Health, Sri Lanka Revised and Expanded
Edition November 2012 ISBN 978 955 0505 35 7
Guidelines on Management of DF & DHF in
children and adolescents Sunethra Gunasena Member of the Guidelines Development Committee,
National Guidelines, Ministry of Health, Sri Lanka
Revised and Expanded Edition November 2012
ISBN 978 955 0505 36 4
Scientific Sessions | MRI Research Day 2014
Prevalence of prolonged and chronic poliovirus
excretion among persons with primary immune
deficiency disorders in Sri Lanka Rajiva de Silva,
Sunethra Gunasena, Damayanthi Ratnayake, GD
Wickramasinghe,
CD
Kumarasiri,
BAW
Pushpakumara, Jagadish Deshpande, Anna Lea
Kahn, Roland W Sutter - Vaccine 2012
http://dx.doi.org/10.1016/j.vaccine.2012.10.035
Case report: First case of vaccine derived
poliovirus isolated from a patient with a primary
immune deficiency in Sri Lanka Sunethra
Gunasena, Rajiva De Silva, Damayanthi Ratnayake, C
D
Kumarasiri,
Jagadish
Deshpande.
Submitted to CMJ for publication
An audit on influenza related complications.
N Dissanayake, P Ratnayake, J Jayamaha, H
Gajaweera, V Madurangi. Annual Scientific Congress
of Sri Lanka college of Paediatricians. August 2013
(First Prize)
Incidence of congenital rubella syndrome /
congenital rubella infection and characterization of
rubella virus from samples presented to MRI. J
Jayamaha, TD Wijerathne, KBR Fernando, WNL
Withanage, G Wickramasinghe, G Galagoda. 22nd
Annual Scientific Sessions of Sri Lanka College of
Microbiologists, July 2013
Analysis of dried blood spots of children with
sensorineural hearing loss due to possible
congenital
cytomegalovirus
infection:
A
preliminary study. J Jayamaha Kin-Chuen Leung A
Keeson W Rawlinson. 22nd Annual Scientific Sessions
of Sri Lanka College of Microbiologists, July 2013
A prospective survey on bacterial and viral
aetiologies of acute lower respiratory tract
infections in children: a preliminary study in a
tertiary care hospital. D C Atukorale, S
Waidyanatha, G K D Karunaratne, J Jayamaha.
Annual Scientific Congress of Sri Lanka college of
Paediatricians. August 2013
Universal newborn hearing screening (UNHS),
sensorineural
hearing
loss
(SNHL)
and
contribution of congenital CMV to the aetiology.
Rawlinson W, Wilkinson M, Hall B, Fennell M,
Cannon M, Jayamaha J, Cottier C & Palasanthiran P.
MRI Research Day 2014 | Scientific Sessions
- Australasian Society for Infectious Diseases Annual
Scientific Meeting. Adelaide, Australia. March , 2014
Trends in Influenza Vaccine Forum of Sri Lanka,
Annual Academic Sessions, Oct 2013
Corona Virus Preparedness in Sri Lanka Seventh
meeting of the national influenza centres and
influenza surveillance in the Western Pacific and
South-East Asia regions, China Nov 2013
Corona Virus Preparedness in Sri Lanka regional
laboratory workshop of influenza and novel viruses,
Pune, India, 26 – 30 may 2014
Measles and SSPE – occurrence and pathogenesis.
Jude Jayamaha. Microbiology Australia September
issue.2013 132-134
Molecular epidemiology of influenza A H1N1
pandemic 2009 virus in humans and swine in Sri
Lanka. Harsha K. K. Perera, Dhanasekaran
Vijaykrishna,
Jude
Jayamaha,
Geethani
Wickramasinghe, Chung L. Cheung, AkuratiyaG.
Premarathna, Ming F. Yeung. Leo L. M. Poon,
Aluthgama K. C. Perera, Ian G. Barr,Yi Guan and
Malik Peiris. Emerging Infectious Diseases Accepted 14-0842
Cytomegalovirus screening of infants with hearing
loss
diagnoses
unsuspected
congenital
cytomegalovirus William Rawlinson Monica
Wilkinson Beverly Hall Michael Fennell Michael
Cannon, Jude Jayamaha Pamela Palasanthiran
Carolyn Cottier. Journal of Clinical Virology,
submitted
The epidemiology of Hepatitis A virus (HAV)
infection based on samples analysed at Medical
Research Institute in 2011. Muthugala MARV,
Galagoda GCS, Jeewanka IGI. 21st Annual Scientific
Sessions, Sri Lanka College of Microbiologists. 2930th August 2012
Age stratified seroprevalence to hepatitis E
infection in samples received at MRI. GCS
Galagoda, Jeewanka IGI. 21st Annual Scientific
Sessions, Sri Lanka College of Microbiologists. 2930th August 2012
77
Follow up of hepatitis B positive volunteer blood
donors at the Medical Research Insitute (20102012). Sumathipala TKGS, Galagoda GCS, Herath
HMAK, de Silva LSL, Jeewanka IGI. Annual Scientific
Sessions, South Asian Association of Transfusion
Medicine. 2012
Incidence of congenital rubella syndrome /
congenital rubella infection and characterization of
rubella virus from samples presented to MRI
Jayamaha J, Wijeratne TD, Withanage WNL,
Fernando KBR, Wickramasinghe G, Galagoda G. 22nd
Annual Scientific Sessions, Sri Lanka College of
Microbiologists. 25-26th July 2013
Establishment of a molecular diagnostic method to
determine the aetiology of meningo-encephalitis.
Danthanarayana NS, Thevanesam V, Galagoda GCS,
Fernando L. 21st Annual Scientific Sessions, Sri Lanka
College of Microbiologists. 29-30th August 2012
Seroprevalence of herpes simplex virus type 2
infection among female sex workers attending
central Sexually Transmitted Diseases (STD) clinic
at National STD and AIDS Control Programme
(NSACP), Colombo. Nakkawita WMID, Mananwatte
S, Galagoda GCS, Kulatunga GGAK. 21stAnnual
Scientific Sessions, Sri Lanka College of
Microbiologists. 29-30th August 2012 and 44th APCPH
Conference. 13-18th October 2012
Low prevalence of IgG antibodies against measles,
mumps and rubella in infants between 6-12 months
of age in Colombo district, Sri Lanka M
Nadhikala, PPSL Pathirana, SM Handunnetti, Sudath
Peiris, GCS Galagoda. Accepted for AISSL sessions
September 2014
Collaborative projects with Buckingham Centre
for Astrobiology, University of Cardiff, UK
Fossil diatoms in a new carbonaceous meteorite
N. C. Wickramasinghe, J. Wallis, D.H. Wallis, Anil
Samaranayake. Journal of Cosmology, Vol, 21, No,37
published, 10 January 2013
Authenticity of the life-bearing Polonnaruwa
meteorite N.C. Wickramasinghe, J. Wallis, N.
Miyake, Anthony Oldroyd, D.H. Wallis, Anil
Samaranayake, K. Wickramarathne , Richard B.
78
Hoover and M.K. Wallis. Journal of Cosmology,
Vol,21, No,39 published, 4 February 2013
Living diatoms in the polonnaruwa meteorite –
possible link to red and yellow rain N.C.
Wickramasinghe,
Anil
Samaranayake,
K.
Wickramarathne, D.H. Wallis, M.K. Wallis, Norimune
Miyake, S.J. Coulson, Richard B. Hoover, Carl H.
Gibson and Jamie Wallis. Journal of Cosmology,
Vol,21, No,40 published, 8 February 2013
Microorganisms in the coloured rain of sri lanka
Anil Samaranayake, K. Wickramarathne, N.C.
Wickramasinghe. Journal of Cosmology, Vol.21,
No.44 published, 13 February 2013
The polonnaruwa meteorite: Oxygen isotope,
crystalline and biological composition Jamie Wallis,
Nori Miyake, Richard B. Hoover, Anthony Oldroyd,
Daryl H. Wallis, Anil Samaranayake, K.
Wickramarathne, M.K. Wallis, Carl H. Gibson and N.
C. Wickramasinghe. Journal of Cosmology, Vol. 22,
No. 2 published, 5 March 2013
Discovery of Uranium in Outer Coat of Sri Lankan
Red Rain Cells Nori Miyake, Takafumi Matsui1,
Jamie Wallis, Daryl H. Wallis, Anil Samaranayake,
Keerthi
Wickramarathne
and
N.
Chandra
Wickramasinghe. Journal of Cosmology, Vol,22, No. 4
published, 15 April 2013
Physical, Chemical and Mineral Properties of the
Polonnaruwa Stones Jamie Wallis, N. C.
Wickramasinghe, Daryl H. Wallis, Nori Miyake, M.K.
Wallis, Richard B. Hoover, Anil Samaranayake,
Keerthi Wickramarathne, Anthony Oldroyd. Presented
in SPIE Astronomical Instrumentation Conference
August 25-29th 2013, San Diego, California, USA.
Dr. Anil Samaranayake (Director, MRI/March 2013)
was appointed as a guest editor of the Journal of
Cosmology, 2013
Scientific Sessions | MRI Research Day 2014
4.1 Ongoing Research Activities
Bacteriology
 A study to determine the circulating serogroups
and the antibiotic susceptibility of Human
Leptospirosis in Western Province, Sri Lanka
 Seroprevalence of Human Brucellosis In Selected
Provinces In Sri Lanka
 Studies on immunodiagnostic methods, immune
status and factors contributing to pathogenesis of
severe leptospirosis in Sri Lanka with clinical
correlation
 Project Title: Comparison of the CLSI method and
a novel technique for the rapid detection of
Extended Spectrum Beta Lactamases (ESBL) in
clinical isolates
 Molecular characterization and comparison of
community acquired MRSA and hospital acquired
MRSA isolates in National Hospital Sri Lanka.
Enteric, Anaerobic, Food and Water Microbiology
and Serology Laboratory
 Antibiotic resistant Patterns of E. coli from water
and Salmonella spp and Staphylococcus spp from
selected food items
 Prevalence of different Salmonella spp in poultry
wet markets & their public health &
epidemiological relationship with Salmonella
isolates of human origin
 Strengthening the National System for ensuring
Microbiological food safety NSF: Thematic project
conducted in partnership with key stakeholders
 Determination of microbial contamination status in
ground and surface drinking water in Kelani river
basin
 An investigation of food borne outbreak among
army soldiers in four military establishments in
North central province Sri Lanka
Entomology
 Developing Statistical Models in computing
Biological effectiveness of Aerosol insecticides
against crawling insects.
Haematology
 Validation of "One tube osmotic fragility test" as a
screening test for Thalassaemia carrier state.
 A study check the stability of in house prepared
Control Blood to be used in Quality Control
Programme for Full Blood Count Testing
MRI Research Day 2014 | Scientific Sessions
Health Information
 Implementation of LIBIMS (Library Information
and Management system) with KOHA Open
Source software
 Computerization of MRI Specimen Counter and
initiation of Laboratory Information System
Histopathology
 Study of the effect of different forms of coconut on
the lipid profiles of healthy free living Sri Lankan
subjects
 Prevalence of Methaemoglobinaemia in patients on
therapeutic doses of nitrates and Nicorandil.
 Analysis of the prevalence of different types of
malignancies in the Jaffna district-A retrospective
study
Immunology
 Genetic diagnosis of X linked
agammaglobulinaemia (XLA) sequencing the btk
mutation
 Diagnosis of specific antibody deficiency in
patients with recurrent lower respiratory tract
infections
 Study determining the pattern of progression of
respiratory colonizers in primary antibody
deficiency patients over a duration of 8 months.
 Identification of the common allergens in children
with asthma and atopic dermatitis Sri Lanka
Laboratory Animal Centre
 Inflammatory and histopathological changes in
Wistar rats given dug well water from high disease
prevalent villages for Chronic Kidney Disease of
Unknown Etiology (CKDu) in the North Central
province of Sri Lanka. MRI funded project.
 Antimicrobial, antibiofilm activity of Sri Lankan
grown Galangal (Alpinia galangal) or
Mahaaraththa against staphylococous auries and its
safety evaluation. NSF funded project.
 Determination of the quality of coconut oil and
health effects of consumption of selected coconut
products. Funded by coconut research institute.
 Identification of active fraction separated from hot
water extract of Tricho santhes cucumerina Linn
for gastroprotection using bio activity directed
separation and their toxicity and isolation of patent
compound's of most active fractions. Funded by
National Research Council.
 Study to assess the suitable bleeding intervals of
sheep without effecting their health status under
local management conditions. MRI funded project.
79
Molecular Biology
 Application of a loop-mediated isothermal
amplification method for the detection of
pathogenic Leptospira from Environmental
samples
 Mutation analysis of patients with Haemophilila
&establishment of the primary database for
Haemophilia mutations in Sri Lanka
 Serotyping of Listeria monocytogenes present in
raw milk collected from collecting centers in
Polonnaruwa District with a focus on food safety
and disease prevention. Sponsored by MRI.
Mycology
 The distribution of Malassezia species in patients
with psoriasis and healthy individuals in Sri Lanka
 Rapid and early detection of Candida spp. by
molecular methods from blood samples from
immuno-compromised patients at National Cancer
Institute, Maharagama
 Screeining of Holarrhena mitis (Kirimawara/
Kalinda/ Kiri-Walla) for antibacterial, antifungal
and larvicidal activity
 Enhancing activity of antimycotics against
common drug-resistant fungal pathogens using tea
compounds
 Antifungal susceptibility pattern of Candida spp.
isolated from Sri Lankan patients
 Susceptibility pattern of yeasts causing
onycomycosis in Sri Lankan patients
 Association of co-morbidities including
sensitization to fungi on severe asthma
 Fungal endophytes from medicinal plant
Sphaeranthus indicus (Asteraceae): a prolific
source of phytochemicals and other bioactive
natural products to discover new drug candidates
 Plumbagin and its semi-synthetic derivatives as
important scaffolds for the treatment of dandruff
 Anti-fungal activity of new essential oils from
indigenous Sri Lankan aromatic plants
 Clinico-mycological profile of dermatophyte
infections in two dermatology clinics in Sri Lanka
Natural Products Chemistry
 Antibacterial activity of some selected local
medicinal plants against antibiotic resistant
bacteria
 Antimicrobial activity and larvicidal activity in
Holerrhena mitis and isolation of bio active
compounds.
80
 Study of the effect of different forms of coconut on
the lipid profiles of healthy free living Sri Lankan
subjects
 Study on safety evaluation of Carica papaya leaf
extract in healthy volunteers.
 Investigation of biological activity of Oldenlandia
umbellate
 Isolation and characterization of bio active
components in Walidda antidysentrica
Nutrition
 National Micronutrient survey on Pregnant
Mothers
 National Dietary Assessment Survey
 Assessment of Food Composition of selected food
Items in Sri Lanka
Parasitology
 Investigation of Automated Slide Scanning
Microscope with Assistive plug-ins.
Rabies & Vaccine Quality Control
 An immunogenicity study on intradermal preexposure rabies vaccination in Sri Lanka.
 Consumption of human rabies immunoglobulin in
government hospitals of Sri Lanka from 20102012.
Virology
 Molecular diagnosis of hantavirus disease among
clinically suspected HFRS (Haemorraghic Fever
with Renal Syndrome) patients in selected
hospitals.
 Comparison of virus isolation with nested
polymerase chain reaction for the detection of
herpes simplex virus in patients with herpes virus
infection
 Detection of Herpes Simplex Virus (HSV), and
Varicella Zoster Virus (VZV), Enteroviruses
(EVs), West Nile (WNV) and Chandipura Virus
Infections in Acute Encephalitis Patients.
 Study on measles, mumps and rubella antibody
status in mothers and their new born babies (in
Colombo District)
 Correlation of hepatitis B and C viral loads with
serological markers in patients with chronic
hepatitis
 Molecular diagnosis of hantavirus disease among
clinically suspected HFRS (Haemorraghic Fever
with Renal Syndrome) patients in selected
hospitals.
Scientific Sessions | MRI Research Day 2014

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