imr bulletin dec 1992

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ui~.t;.mber 1992 No, 29

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Page 1: IMR Bulletin Dec 1992

ui~.t;.mber 1992

No, 29

Page 2: IMR Bulletin Dec 1992

ISSN: 0127-0265

6 KANDUNGAN - Perlindungan diri terhadap nyamuk ........................................................................ 1

Dot-immunobinding assay untuk pengesanan Rickettsia t.slrts~igar?zli.s lri di ddani vektornya ....................................................................... 3

Jangkitan Saluran Pernafrisan Akut : k:tji;ln halangan berasas masyarakat ...................... .. ....................................................................................... 4

. . ............................................................................................... Program Imniunisasi 5

............................................................................. Abstrak-abstrak penerbitan IMR 6

Tesis-tesis Doktor Falsafiih .................................................................................. 9

............................................................ Diploma Teknologi Makmal Perubatun 14

Bahagian Ternaknn dan Penyelidikan Haiwan Makmal. IMR ............................... 15

................................................................................................ Kursus d m Bengkel 17 i

- CONTENTS Personal protection against mosquitoes ..................................................................

A Dot-inmunobinding assay for detection of Rickettsia tsutsngamuslzi in its .................................................................................................................... vectors:

Acute Respiratory Infection in children : a community-based intervention study ........................................................................................................................

The Inimunization Progmmme ...............................................................................

Abstracts of publications .........................................................................................

Ph . D . theses ............................................................................................................

Diploma i n Medical Laboratory Technology .........................................................

The Division of Laboratory Animal Resources, Ih4R ............................................

Courses and Workshops .........................................................................................

GAMBAR KULIT Kelarnbu direndam d d a m pem~ethrin. dijemur dan digunakan .

COVER PIIOTOS Preparation and use of perniethrin impregnated bednets .

Page 3: IMR Bulletin Dec 1992

Nyamuk tersebar dengan meluas di kawasan bandar dan luar bandar di Malaysia. Nyamuk memainkan peranan penting dalam penyebaran penyakit jangkitan vektor seperti malaria, denggi, untut-untut dan Japanese Encephalitis. Selain membahayakan kesihatan manusia, nyamuk boleh mengakibatkan ketidakselesaan dan gangguan tidur.

Langkah-langkah kawalan vektor yang teratur seperti semburan DDT di dalam rumah sebagai langkah utama pengawalan antimalaria, penyemburan udara termasuk penyemburan ULV dan termal fogging malathion telah dijalankan semasa perebakan wabak denggi, Japanese Encephalitis dan kes-kes malaria. Peringkat larva juga dikawal dengan malathion dan abate bert~~juan menghapuskan tempat- tempat pembiakan vektor-vektor ini. Walau bagaimanapun, langkah-langkah ini masih tidak mencukupi kerana masalah operasi dan Iialangan-halangan lain. Tarnbahan pula, kesan penyemburan racun serangga terhadap alam sekitar dalam program pengawalan nyamuk telah dipersoalkan kebelakangan ini. Oleh itu pendekatan alternatif bagi melindungi manusia dari gigitan nyamuk telah diberi keutarnaan.

Timbulnya peningkatan kesedaran untuk strategi pengawalan perlindungan diri yang murah dan ia boleh digunakan pada tahap komuniti. Beberapa teknik perlindungan diri telah wujud, yang mana jika dig~lnakan berterusan boleh mengurangkan hubungan di antara nyamuk dengan manusia dan bagi kes- kes tcrtentu telah mengurangkan populasi

nyamuk. Berbagai cara perlindungan diri sedang digmakan di pelbagai keadaan.

Penggunaan repelan (bahan penolak serangga) ke atas baju atau kulit merupakan cara terbaik untuk perlindungan di luar rumah. DEET (Dietil toluamid - repelan paling biasa) dan piretroid seperd del tamethri11 darj per n~e~hl in , apabila digunakan untuk perendaman jaket, 'anklet', 'wristband' dan 'headband' dapat memberikan kesan terhadap vektor nyamuk tempatan seperti yang telah ditunjukkan oleh kajian di Institut Penyelidikan Perubatan (IMR). DEET dan repelan-repelan lain boleh juga digunakan kepada kulit (terutamanya di sekeliling leher, buku lali dan pergelangan tangan) untuk perlindungan tambahan. Terdapat sekurang-kurangnya 8 jenama repelan tempatan yang b e r b e ~ a holeh d i d a p t i di pasaran negara, tetapi tidak semua memberikan keberkesanan seperti yang didakwa oleh syarikat yang terbabit.

Sejenis formula repelan baru, Mosbar dari Australia mengandungi permethrin dan DEET telah dikaji dari segi kuasa penolakannya dan kesan insektisidal terhadap vektor tempatan dan nyamuk yang mengganggu oleh saintis IMR dan mendapati bahawa Mosbar merupakan satu bahan yang murah, boleh digunakan dalam jangka masa yang panjang (sehingga kepada 8 jam untuk setiap penggunaan) dan didapati herkesan.

Lingkaran nyamuk, kepingan perlowapan dan penggunailn aerosol di dalam rumah telah

Page 4: IMR Bulletin Dec 1992

Artikel Utama

menunjukkan keherkesanannya dan boleh didapati dengan meluas di Malaysia. Pada semua produk insektisid tersebut yang digunakan di dalam rumah yang dijual di Malaysia ini , insektisid piretroid telah digunnkan sebagai bahan aktif kecuali beberapa jeriis yang rnenggunakan kombinasi karbamat dan/atau organofosforus. Terdapat had dalam penggunaan kepingan perlowapan (10 jenama ada dljual d i Malaysia) kerana ia mesti disclitkan kepada pemanas kecil untuk rnelepaskan wap repelan tersebut. Lingkaran nyamuk (15 jenama) menghasilkan asap untuk menolak nyamuk. Semburan udara dengan aerosol di dalam rumah (sekurang-kurangnya 15 jenama) selalunya mengandungi sintetik piretroid, yang boleh membunuh nyamuk di persekitaran t e m p t tidnr. Namun hegitu, alat yang mengeluarkan bunyi ('buzzer') tidak berkesan untuk menolak nyamuk di makmal dan juga di lapangnn.

Halangan terhadap hubungan di an tara manusia dan nyanluk vcklur rnasih rnerupakan langkah perIu terutamanya terhadap spesis yang menggigit pada waktu malam, iaitu apabila seseorang terdedah kepada serangan nyamuk semasa tidur. Kelambu telah lama digunakan untuk tujuan ini, tetapi hanya kebelakangan ini ia telah diperlakukan dengan racun serangga yang berkesan boleh membunuh nyamuk dan juga menghalau mereka. Malahan, barangan yang murah dan mudah ini telah menambahkan minat terhadap langkah-langkah perlindungan ke atas nyamuk pembawa paracit kehelakangan ini.

Pada tahun 1990, satu kajian telah dimulakan oleh IMR untuk mengkaji kesan penggunaan kelambu berubat permethrin terhadap

ketumpatan vektor dan kekerapan berlakunya malaria di kalangan Orang Asli di Pahang, Semenanjung Malaysia. Kajiselidik yang dijalankan pada permulaan projek ini (19901 1991) untuk menganalisa hubungan di antara kejadian malaria dan penggunaan kelambu di kalangan penduduk tempatan menunjukkan bahawa penggunaan kelarnbu telah memberi perlindungan terhadap malaria. Kadar jangkitan malaria bagi setiap orang setiap bulan adalah rendah bagi mereka-mereka yang menggunakan kelambu. Keputusan pos kawalan yang didapati selepas pengagihan kelambu berubat permethrin menunjukkan terdapat penurunan yang signifikan terhadap kes-kes nlalaria dan juga kadar inokulasi sporozoit nyamuk di kawasan yang dikaji. Percubaan ini dan percubaan-percubaan kecil yang lain di Malaysia dan juga di negeri lain telah menjelaskan kesahihan penggunaan kelambu berubat sintetik pyretroid boleh mengurangkan perhubungan di antara vektor malaria dan kadar berlakunya jangkitan. Begitu juga penggunaan langsir berubat yang menutupi 'eaves', pintu dan tingkap telah nienujukkan pengurangan gigitan nyamuk di dalam mmah, walaupun kurang berkesan j ~ k a dibandingkan dengan penggunaan kelambu.

Langkah tambahan terhadap perlindungan diri untuk mengurangkan hubungan nyamuk- manusia termasuklah memperbaiki sistem perumahan seperti pemasangan skrin perlindung d i t ingkap dan pintu atau menggantikan bnluh dan rotan dengan kayu yang lebih padat sebagai lantai dan dinding, dan pemilihan tapak pembinaan rumah sama ada untuk tinggal sementslra atau tctap tidaklah berdekatan dengan tempat pembiakan nyamuk.

Page 5: IMR Bulletin Dec 1992

Dot-Immunobinding Assay untuk pengesanan Rickettsia tsutsugtamushi di dalam vektornya

Rickettsia rsutsugamushi adalah organisma yang menyebabkan penyakit tifus skrub. Penyakit itu adalah endemik di Asia Tenggara dan disebarkan melalui gigitan jejentik beberapa jenis hamama. Jejentik itu juga dikenali sebagai tungau. Terdapat 3 spesis vektor d i Semenanjung Malaysia, iaitu Leptotrombidium deliense, Leptotrombidium fletcheri dan Leptotronzbidium arenicola. Kesemua vektor itu wujud dalam dua bentuk populasi yang berbeza, iaitu satu populasi berjangkit yang boleh men yebarkan pen yakit dan satu lagi populasi yang tidak. Bagi mengenalpasti risiko tifus skrub di sesuatu kawasan, adalah penting untuk menentukan samada tungau yang terdapat di kawasan tersebut terkena jangkitan atau tidak.

Pengesanan jangkitan tifus skrub didalam tungau biasanya dilakukan melalui pemencilan dalam haiwan perurnah dan 'direct fluorescent antibody technique' (DFAT). Teknik yang pertama itu memerlukan masa yang panjang. Tcknik yang kedua n~emerlukan mikrvskop fluorescent yang mahal dan juga kepakaran untuk menganalisa hasil ujian. Kedua-dua teknik mi tldak boleh digunakan di medan.

Kebelakangan ini sebuah 'Dot-Immunobinding Assay' (DIBA)' telah diperkernbangkan dan didapati tidak mempunyai kelemahan seperti teknik-teknik diatas. Teknik ini ditunjukan dalam gambarajah 2 (mukasurat 28) . Pada asasnya, ekstrak tungau dititikkan ke atas cakera kertas turas asitat selulosa. Cakera itu kemudiannya dikeringkan dan direndamkan dalarn larutan 5% susu skim selama 1 jam. Susu itu bertindak menyekat pem~ukaan cakera

yang tidak dilapiskan dengan ekstrak tungau. Larutan susu dikeluarkan dan dimasukkan pula serum hiperium daripada arnab yang telah diimunisasikan dengan R. tsutsuigamushi.

Selepas pengeraman 2 jam, antiserum itu dikeluarkan dan cakcra itu dibasuh dengar1 larutan 'Tris balanced saline' (TBS). 'Goat anti-rabbit immunoglobulin peroxidase conjugate' kemudian ditambah dan dieramkan selama 2 jam. Selepas pengeraman, cakera dibasuhkan dengan TBS lagi. Larutan substrat 'diaminobenzidine tetrahydrochloride' di tambahkan. Selepas 30 minit pengeraman, larutan substrat dikeluarkan dan cakera dikeringkan semalaman pada suhu bilek. Cakera yang mengandungi ekstrak tungau posirif akan menmjnkkan titik keperangan dan

jika tidak menunjukkan sebarang warna, ekstrak tungau itu adalah negatif (gambarajah 1, muknsurnt 27).

DIBA mempunyai dua kelebihan untuk mengesnn tungau yang mempunyai jangkitan berbanding dengan dua reknik yang terdahulu. Teknik ini mudah digunakan di medan dan keputusannya adalah kckal dan boleh disimpan untuk rujukan. Sebuah kit prototip sedang diperkembangkan dan adalah sesuai digunakan walaupun oleh pegawai kawalan vektor yang tidak berpengelaman dalam kerja-kerja makmal. DIBA tidak boleh mernbezakan strain-strain R. tsutsugainushi. Teknik ini hanya digunakan sebagai pengesanan pendahuluan untuk jangkitan tifus skrub dalarn tungau. Strain R. tsutsugamushi yang terlibat selepasnya bolehlah ditentukan dengan cara DFAT.

Page 6: IMR Bulletin Dec 1992

( Jangkitan Saluran Pernafasan Akut : kajian halangan berasas masyarakat

e Munn Snnn

Sa tu kajian 'longitudinal' di jnlankan ke atas masyarakat kampong di Kelantan untuk menilai kesan terhadap 2 intervensi iaitu pendidikan kepada ibu-ibu untuk mengenali tanda-tanda jangkitan saluran pernafasan akut (ART) pa& anak-anak mereka, dan latihan kepada kakitangan hospital dan kesihatan oleh pakar pediatrik dalam pengurusan kes ARI yung bertujuan untuk mengurangkan pengidap ARI yang teruk di kalangan kanak-kanak.

Daerah Pasir Mas telah dipilih sebagai kawasan halangan manakala Daerah Machang dan Pasir Puteh yang mempunyai sosiodcmografi yang hampir sama telah dipilih sebagai kawasan kawalan. Sejumlah 25 buah kampung telah dipilih secara rawak diset iap kawasan. Sejumlah 4378 kanak-kanak dibawah umur 7 tahun telah disusuli selama 2 minggu sekali dalam kajian dari rumah ke rumah selama 1 tahun. Dalam tempoh yang sama, terdapat sejurnlah 1 1,483 kes rawatan ARI dari Hospital Daerah, Pusat Kesihatan dan Klinik Bidanmesa telah diteliti unruk mengetahui ketenatan penyakit dan juga pengurusan kes rawatan.

Sebanyak 4460 dan 4238 episod ARI telah dikesan daripada kajian dari rumah ke rumah di kawasan halangan dan kawalan masing-masing yang mana memberi insiden keseluruhan tahunan sebanyak 1.98 episnd bagi setiap kanak-kanak. Insiden di kawasan halangan adalah sebanyak 1.9 episod bagi setiap kanak- kanak (4460/2406) dan 2.1% (4238/1972) di kawasan kawalan. 34% daripada kanak-kanak telah mendapat satu episod ARI, 21% 2 episod, manakala 45% telah menghidapi 3 alau lcbih episod ARI. Majoriti (42%) episod berakhir

selepas 2-3 hari. Tiada variasi bermusim dikesan di 2 kawasan, 97% episod ARI yang ringan, 1% peringkat pertengahan dan 2% di peringkat teruk. Keadaan ini hampir sama di 2 kawasan kajian.

Setelah perbandingan dibuat dalam bentuk nisbah hagi epiwd yang teruk dalam tempoh 2 bulan pertama dan 2 bulan terakhir kajian, terdapat pengurangan besar dalam kes ARI diperingkat teruk (62.7%) di kawasan halangan berbanding dengan pengurangan sebanyak 15.4% di kawasan kawalan (p<0.01). Daripada jumlah 11,483 episud ARI dari kawasarl halangan dan kawalan yang telah dirawat di Pusat Kesihatan kerajaan, Hospital Daerah dan Hospital Besar Kota Bharu didapati 65% diperingkat ringan, 32% pertengahan dan 3% yang teruk. Di kawasan intervensi, 10% jangkitan ARI peringkat ringan telah diberi antibiotik, berbanding dengan 25% di kawasan kawalan.

Pengurangan dalam nisbah yang begitu ketara bagi ARI peringkat teruk dapat dilihat di kawasan halangan. Ini kerana kurang penggunaan antibiotik yang tidak sesuai di kawasan intervensi berbanding dengan kawasan kawalan. Keputusan ini memberi kesan penting dalam program pengawalan jangkitan ARI di Malaysia.

Kajian ini dijalankan oleh:

Idye M S , lJmn D, I.ni P F , I j n n j ~ ~ t K, Chon KE, Azmi

Shapie, Atmi Hashim, Wan Mansor H , Fatimah D ,

Chong CY, Nor Azmi, Thevaraj S, Abdul Aziz Mahrnud, Jit Singh, Laila Noor, Azizan Aiyub Ghazali dun Anuar

Bachee.

Page 7: IMR Bulletin Dec 1992

Kesihatan

( Program Imunisasi

Imunisasi atau pclalian inlah satu cars yang paiing berkesan dan menjimatkan dalam mengawal penyakit-penyakit berjangkit. Olih kerana pentingnya imunisasi, WHO telah memperkenalkan Program Pelu asan Imunisasi (Expanded Programme of Immunization ataupun EPI) pada tahun 1974. Objektif EPI ialah untuk mengurangkan morbiditi, kematian dan kecacatan, disebabkan olih penyakit- penyakit seperti difteria, batuk kokol, tetanus (kancing gigi), polio, campak dan tibi. Untuk mencapai objektif itu program imunisasi dilancarkan supaya memberi perlindungan vaksin kepada bayi-bayi serta ibu-ibu mengandung.

Di Malaysia, imunisasi diberikan secara rutin uriluk rriengclakkan penyakil-penyakit kanak- kanak yang tersebut. Tambahan pula, imunisasi rubella dilancarkan pada tahun 1988 dan imunisasi terhadap Hepatitis B dimasukan kedalam Program Imunisasi Kanak-Kan'ak pada tahun 1989 (lihat Gambarajah). Ciri khas dalam program imunisasi itu ialah ianya diberi secara percuma di hospital-hospital dan klinik kerajaan, tetapi tidaklah wajib dari segi undang- undang.

Program imunisasi diperingkat kebnngsaan diselaraskan dan disediakan oleh Bahagian Kesihatan, Kementerian Kesihatan. Unit Kesihatan Ibu dan Kanak-Kanak dari Bshagian tersebut menyelaras d m menyelia aspek-aspek pengurusan perkhidmatan imunisasi. Penilaian program, pengawalan vaksin serta pengawasan potensi adalah tanggungjawab Unit Epidemiologi dengan kerjasama Institut

Penyelidikan Per-ubalari. Pernbclian, penyim- panan dan pengedaran vaksin dikawal oleh Stor Perubatan, Kementerian Kesihatan. Kesan Program Imunisasi Kebangsaan bolih dilihat dari kejadian itu yang semakin berkurang dari tahun ketahun dengan pencapaian liputan imunisasi.

Sejak perlaksanaan perkhidmatan imunisasi secara rutin pada awal tahun 1970, kejadian penyakit-penyakit berjangkit telah berkurang dengan berkesan. Kes difteria dilap.~~rkan telah berkurang daripada 230 pada tahun 1976 kepada 9 kes dengan 1 kematian pada tahun 1990. Icejadian kcs batuk kokol pada 1976 adalah 300 kes berbanding dengan 24 kes dilapur pada 1990. Kes tetanus neonatorium telah berkurangan kepada 15 hingga 20 tiap- tiap tahun. Sejak 1986 tiada kes poliomyelitis telah dilapurkan.

Selaras dengan tujuan untuk mencapai objektif Imunisasi Kanak-Kanak Sedunia (UCI) pada 1990 berbagai strategi telah dilancarkan pada 1989 untuk meningkatkan pelalian. Akibatnya liputan pelalian hagi 'Triple' dan polio telah meningkat daripada 72 peratus pada 1988 kepada 80 peratus pada 1990 dengan mencapai tahap objektif UCI. Tetapi liputan pelalian measles masih belum mencapai 8 0 peratus. Kes-kes tahunan measles adalah diantara 2000 hingga 5000. Bagi mengatasi nmaalah iru, Bahagian Kesihatan telah memperkenalkan jadual pelalian baru pada 1991 yang mewajibkan pelalian measles sebelum harijadi yang pertama.

Page 8: IMR Bulletin Dec 1992

Penerbitan IMR

Kementerian Kesihatan juga telah merancang Kelantan dibawah satu projek R&D. Dengan berbagai program untuk menilai EPI. Satu program imunisasi yang lebih intensif, daripada program itu ialah Serosurvey Malaysia akan terus berusaha untuk mencapai Masyarakat, yang sedang dijalankan olih IMR objektif WHO ,iaitu 'Kesihatan untuk Semua dengan kerjasama Universiti Sains Malaysia di sebelum Tahun 2000'.

Sejarcth program imunisasi di Malaysia

1. Smallpox

2. D.T.(Diphtheria & Tetanus)

3. D.P.T. (Diphtheria, Pertussis & Tetanus)

4. B.C.G.

5. Poliomyelitis

6. Tetanus toxoid (bagi ibu mengandung)

7. Measles

8. Rubella

9. Hepatitis B

Dilaksanilkan pada 1950 d m dihcntikan pada 1980.

Diperkenalkan pada 1955.

Diperkenalkan pada 1958.

Diperkenalkan pada 1962.

Diperkenalkan pada 1972 setelah wabak.

Diperkenalkan pada 1974.

Diperkenalkan pada 1982.

Diperkenalkan pada 1988.

Diperkenalkan pada 1989

Menilai perencatan paras hormon Med J Malaysia 1992; 47(2): 103-9 tumbesaran selepas ujian tolerans ghk0s (75g). Objektif kajian ini adalah untuk rnenggunakan

radioimunoasai (RIA) yang dibangunkan W a n Nuzaimoon W a n Matmod, M L Ng, N sendiri bagi tujuan menilai kespesifikan ujian Si;tgunasirzgilm d m Khalid Kadir. toleransi glukos oral (OGTT) untuk merencat

Page 9: IMR Bulletin Dec 1992

Penerbitan IMR

rembecan hor rnon turnhesaran (GH) wlepau I dan 2 jam, pada subjek normal dan pesakit- pesakit 'impaired glucose tolerance (IGT)' diabetik (IDDM) d m akromegalik. Di samping itu, suatu nilai 'cut-off' untuk GH semasa OGTT akan diperolehi berdasarkan RIA yang dibangunkan sendiri ini. Kepurusan kajian ini mendapati paras nadir GH pada jam 2 selepas OGTT untuk subjek normal adalah antara 0.4- 8.4 mIU/L, manakala jarak keyakinan 95% adalah 0.4-4.41U/L. Paras GH berpuasa dan semasa OGTT pada subjek IGT d m IDDM tidak berbeza daripada subjek normal. Sebaliknya, paras GH berpuasa pada pesakit akromegalik didapati sangat tinggi (1 1 .%I78 mIU/L), d m rembesannya tidak terencat oleh, glukos. Oleh yang demikian, kajian ini jelas menunjukkan bahawa pengesahan diagnosis penyakit akromegali hendaklah dilakukan dengan OGTI'.

Corak calitan putus haid - kajian semula calitan vagina 480 orang, wanita

R Pillny, SK Yop don GI. Lim

Med J Malaysia 1992; 47: 33-43

Projek ini bertujuan rnenentukan pola corak sitohormon wanita normal, yang putus haid asimptomatik. Sejumlah 480 calitan vagina wanita yang berurnur 36-74 tahun dikaji untuk menentukan corak sitohormon daripada calitan VCE yang diterima untuk saringan rutin bagi kanser servikal. 50% menunjukkan calitan atrofik yang sejajar dengan kekurangan hormon estrogen. 41% menunjukkan calitan dalam peringkat kurang proliferatif ke poliferatif sederhana bersesuaian dengan rangsangan estrogen yang suboptimal. 9% menunjukkan corak proliferatif pesat iaitu ciri kesan estrogen tanpa tentangan, dan dalnm kumpulan ini, satu

hiperplasia endometrial dan satu adeno- karsinoma-in-situ ditemui. Kajian ini menunjukkan status hormon perempuan postmenopausal tidak bergantung kepada umur atau tempoh menopause. Penilaian sitohormon berguna untuk menentukan perempuan yang harus menjalani tcrapi periggaritia~l hunnun dan dalam mengenalpasti wani ta yang rnernpunyai risiko patologi endometrial.

Kesan pi1 perancang campuran berdos rendah ke atas henmtokrit clan kelekitan darah

Roshidah Islzak, CK Lolz, Khalid Hassan dan Henry R Gr~dum

S a t u penyelidikan 'cross-sectional' yang mengkaji kesan pi1 perancang (PP) campuran berdos rendah relah dijalankan ke atas 43 wanita, 27 daripadanya pengguna PP manakala 16 bukan pengguna PP, yang bertindak sebagai kawa lan . Pengguna PP di bahagi kepada 2 kumpulan : kumpulan 1 terdiri daripada 16 wanita yang mengambil PP yang mengandungi 30ug ethinyloestradiol + 150ug dosegstrel, setiap hari selarna 1 tahun atau lebih dan kumpulan 2 terdiri daripada 11 wanita yang menggambil PP yang mengandungi 30ug ethinyloestsadiol + 150ug levonorgestrel setiap hari bagi jangkamasa yang sama. Terdapat peningkatan yang signif'ikan ke atas hematokrit (p<0.001) dan kelekitan darah (p<0.05) didalam pengguna PP yang mengandungi levonorgestrel (sebagai progestrogen) tetapi kesan yang sama tidak didapati pada pengguna PP yang niengandungi desogestrel (sebagai progestrogen) yang digunakan di dalam campuran PP dos rendah yang diselidiki. Penemuan ini mengambarkan perlunya diawasi

Page 10: IMR Bulletin Dec 1992

Penerbitan IMR

wanita yang nlengambil PP untuk jangka-masa yang panjang untuk mengw~ijudkan indikator yang sesuai, supaya keputusan untuk memberhentikan penggunaan PP holeh dibuat

terhadap PP yang berkemungkinan meningkatkan risiko kepada trombosis.

Kekurangan Alpha-1-antitrypsin dikalangan bayi yang niengalanii jaundis berpanjangan.

Zakiah Isrnail, Mohd Znirzi Abd Raltman, Jarnilah Baftronz dar~ Znwinh Ah~nntl

Malaysian J Pathol 1992; 14(2): Y l - 3

n a l a r n rernpoh tiga tahnn, kami telah mengkaji secara rawak 310 orang bayi yang masuk ke Hospital Besar Kuala Lunlpur akibat jaundis bcrpanjangan. Objektif utama ktj ian in i ialah untuk mengkaji insiden kekurangan Alpha-1-

antitrypsin di kalangan bayi tersebut kerana telah diketahui bayi yang menghadapi rnasalah ini boleh mengalami jaundis berpanjangan di peringkat umur awal Semhilan puluh dua (29.7%) orang bayi didapati mengalami masalah kekurangan Alpha-1-antitrypisin ini. Peratus insiden tertinggi adalah di kalnngan bangsa India (33.3%), diikuti dengan Melayu (3 1.9%) dan Cina (26.7%). Kecenderungan masalah ini d i kalangan lelaki juga diperlihatkan dengan nisbah insiden 1elaki:perempuan adalah 1.6: 1. Kebanyakan bayi ini berumur antara dua minggu dan satu bulan. Selain masalah jaundis dan kekurangan Alpha- 1 -antitrypsin, 2 orang mengalami masalah pendarahan, 11 orang mengalami infeksi d m 3 orang mengalami masalah pernafasan. Dua orang bayi menunjukkan sifat sindrom Down dan 2 orang lagi mengalarni masalah kekurangan G6PD. Manakala paras AST, ALT dan ALP04 didapati tinggi masing- masing dalam 20, 26 dan 3 orang bayi.

Malay Chinese Indian Others

Race M = Male

F = Female AIATD Normal

Distribusi barlgsa darz jantina bayi jnnndis yang mengalanzi kekurarzgan Alpha-1-antitrypsin

Page 11: IMR Bulletin Dec 1992

Tesis Doktor Falsafah

[ Penggunaan klinikal penentuan Hormon Turnbesaran Manusia

(Absti-ak dari Tesis yang di kemukakan ke Universiti Kebangsaan Malaysia oleh Wan Nazaimoon Wan Mahmud pada tahun 1991 bagi ijazah Doktor Falsafah)

Fungs i cndoluin hipotalarnik-pituitari boleh dinilai samada dengan ujian asas, atau rangsangan/rencatan dinamik, dan dengan penentuan paras hormon peptid pituitari seperti hormon tumbesaran (GH) d m prolaktin (PRL). Pengukuran paras GH dalam serum adalah cara yang paling kerap digunakan untuk mengesahkan diagnosis kekurangan GH yang mengakibatkan perturnbuhan terencat, dan kelebihan G H dalam penyakit akromegali.

Dengan penghasilan antibodi poliklonal primer dan sekunder yang begitu spesifik, radioimunoasai (RIA) dan enzimimunoasai (ELSA) untuk GH, serta RIA untuk PRL telah diwujudkan. Kesahihan dan kebolehan asai- asai sendiri ini telah dibuktikan dalarn ujirin pcngcmbalian, kelinearan d m kebolehulangan.

Paras G H berpuasa (FGH) di kalangan orang normal, dipengaruhi oleh umur dan jantina. Semasa prabaligh, paras FGH pada kanak- kanak perenlpuan adalah lebih tinggi berbanding kanak-kanak lelaki (p<O.OS). Bagaimanapun, perbezaan sedemikian tidak lagi ketara di kalangan kanak-kanak baligh dan orang dewasa. Manakala paras FGH pada semua kanak-kanak normal dalanl peringkat Tanner 1 hingga 4 menunjukkan korelasi yang sangat signifikan dengan ketinggian (r=0.304, p<0.001), paras FGH pada kanak-kanak lelaki

sahaja didapati berkorelasi signifikan dengan paras testosteron (r=0.358, p=0.006).

Pada kedua-dua jantina, para5 FGH adalah paling tinggi pada kanak-kanak peringkat Tanner 2 hingga 4 dan kumpulan dewasa muda, kemudian menurun, dan berada di tahap rendah apabila umur semakin meningkat (p<0.001). Oleh demikian, julat rujukan untuk FGH telah disediakan mengikut jantina untuk kanak-kanak prabaligh, mengikut peringkat Tanner bagi yang sudah baligh dan mengikut umur untuk orang dewasa (Jadual).

normal.

GH Berwuasa (mIU/L Jarak Kevakinan 95 %

Prabaligh Lel aki 0.5 - 13.2 Perempuan 1.3 - 17.6

Baligh Tanner 2,3,4 1.4 - 44.0 Tanner 5 0.5 - 25.6

Dewasa 21 -44 tahun 0.4 - 18.2 45 - 8 1 tahun 0.4 - 4.0

Page 12: IMR Bulletin Dec 1992

Tesis Doktor FaIsafalt

Kegunaan klinikal ujian rangsangan jenis fisiologi, iaitu senaman dan Bovril juga dikaji. Kira-kira 25% orang dewasa normal menunjukkan respons terhadnp kedua dun rangsangan ini. Sebaliknya, hanya 2% subjek obes menunjukkan respons terhadap rangsangan senaman, msnakala tiada seurlirig pun terhadap Bovril. Di kalangan kanak-kanak lelaki normal peringkat baligh pula, kadar respons terhadap senaman dan Bovril masing- masing adalah 50 d m 0%. Walaupun ada sekumpulan kanak-kanak lelaki baligh yang tidak menunjukkan respons terhadap rangsangan, mereka telah pun mempunyai paras FGH yang tinggi (>17mIU/L), menunjukkan pengeluaran GH yang mencukupi. Oleh yang demikian, pengukuran paras asas FGH penting semasa mentafsirkan keputusan ujian dinamik.

Paras FGH pnda kanak-kanak berinalnutrisi ringan dan sederhana tidak berbeza daripada kanak-kanak normal (peringkat Tanner yang sama). Bagaimanapun, kesan malnutrisi didapati mempengaruhi paras 'insulin-like

growth factor' (IGF-I), pada kanak-kanak prabaligh. Paras IGF-I menurun dengan signifikannya (p<0.01) mengikut penurunan indeks jirim badnn.

Sesetengah penyakit endokrin yang berkaitan dengall intvle~ails glukvs bole11 meinpengaruhi paras FGH. Oleh kerana paras FGH sangat berbeza, kajian ini telah membuktikan bahawa ujian tolerans glukos (OCirl"l') perlu untuk rnengesahkan diagnosis kelebihan GH pada pesakit akromegalik. Sementara itu, paras median FGH pada pesakit diabetes yang bergantung pada insulin (IDDM), muda (1 8-44) dan tua (45-81), adalah lebih tinggi berbanding subjek normal sebaya (p<0.001). Pada kumpulan IDDM, paras FGH berkorelasi positif dengan paras hemoglobin terglikat (gHb), menunjukkan kaitan dengan intolerans glukos. Bagaimanapun, paras FGH didapati normal pada pesakit diabetes yang tidak bergantung pada insulin (NIDDM). Maka, pengukuran GH, samada paras asas atau selepas rangsangadrencatan, sangat penting dalam pelbagai penyakit endokrin.

Kajian seroepidemiologi, imunologi, dan molekular infeksi Mycobacterium leprae.

(Abstrak Tesis yang dikemukaknn oleh Gan Seng Chew ke Universiti Malaya pada April 1991 bagi ijazah Doktor Falsafah)

H a s i l kajian seroepiderniologi, imrnunologi, juzuk- juzuk berhubung selaput sel seperti dan molekul infeksi Mycobucterium leprue fenolik glikolipid (PGL) dan lipoara- dibentangkan. Selaput sel M. leprae d m binomannan R (1,AM R ) amat sangat

Page 13: IMR Bulletin Dec 1992

Tesis Doktor Falsafah

immunogenik, mengakibatkan balasan humoral antibodi yang kuat dan penindasan in~munity sel.

Hasil kajian seroepidemiologi kebangsaan untuk tiga tahun berturut-turut yang melibatkan lebih kurang 40,000 individu tcrpilih sccara rambang menunjukkan ujian P G L immunoassay boleh digunakan sebagai alat rapisan dalam rancangan kawalan kusta. Keadaan sifat serpositif dengan antigen PGL ada perhubungan dengan kadar kekerapan sesuatu populasi tertentu. Kegunaan antigen M. leprae yang spesifik, seperti PGL, dalam immunoassay boleh digunakan sebagai suatu penunjuk infeksi M. lepme.

Individu-individu yang berinfeksi subklinikal berada titer antibodi yang tinggi dan boleh diasingkan daripada mereka yang immun. Titer antibodi yang tinggi, khasnya dalam kelas IgM, terdapat dengan frekuensi yang tinggi untuk individu-individu yang tinggal di komuniti dengan kadlir kekerapan yang tinggi dan dar i pesakit-pesakit kusta. Antibodi IgG terdapat dengan kuantiti yang bererti di individu- individu yang tinggal di konluniti dengan kadar kekerapan yang rendah dan pesakit-pesakit kusta yang lama berubat. Siiatu ujian agglu tinasi butir-bu tir gelatin yang menentukan IgM-anti-NT-BSA digunakan sebagai ujian lapangan dalam kajian seroepidemiologi kebangsaan dan keputusan yang diperolehi menunjukkan persesuaian yang baik dan adalah setaraf dengan ELISA sebagai ~ljian penunjuk.

Balasan limphosit pesakit-pesakit lepromatous (LL) kepada antigen-antigen M. leprae, BCG, dan PPD adalah lebih kurang bila dibandingkan dengan balasan olih pesakit-pesakit tuberkuloid (TT). Ini menunjukkan lymphosit dari pesakit- pesakit LL dapat mengenal antigen-antigen BCG dan PPD yang ada persamaan dengan M. leprae. Maka tidakan balasan T sel olih LL adalah khas kepada antigen-antigen M. leprae. Dari persemian in vitro sel-sel limpa tikus yang telah disuntikan dos booster dengan antigen- antigen M. leprae menunjukkan kekurangan jenis sel CD45RA+CD8+, harusnya olih kerana pembentukan cytotoxic effectors da lam kumpulan sel CD45RA-low CD8.

Suatu perpustakaan genom dari M. leprae yang diasingkan secara langsung dari biopsi pesakit kusta telah dibina. Ini adalah berbeza dari perpusrakaan genom yang sedia ada dimana DNA yang digunakan adalah dipencilkan dari M. leprae yang tun-rbuh secara eksperimental pada armadillo. Sejumlah 39 klon yang reaktif secara immunologik telah dikenalpasti. Sernua klon-klon tersebut telah diidentifikasi dengan serum pesakit kusta jenis L L yang dikumpulkan. Sementara 3 dari klon-klon tersebut juga telah diidentifikasikan dengan serum pesakit kusta jenis T T dan BT yang dikumpulkan. Kajian lanjut sedang dijalankan bagi mengenalpasti epitop yang antigenik dan berupaya untuk merangsang immunity yang bersifat protektif.

Page 14: IMR Bulletin Dec 1992

Tesis Doktor Falsafah

Production and characterization of monoclonal antibodies

(Abstrak tesis yang dikemukakan ke Universiti Malaya oleh Patricia Lim Kim Chooi pada September 1991 untuk ijazah Doktor Falsafah)

Objektif kajian ini adalah untuk menghasilkan antibodi-antibodi monoklonal terhadap parasit- parasit malaria Plasmodium falciparum dan Plasmodium cynomolgi untuk digunakan dalam immunodiagnosa dan mengidentifikasikan epitope-epitope antigen yang mungkin terlibat dalam perlindungan immun hos. Antibodi- antibodi monoklonal terhadap antigen skizon P. falciparum dan P. cynomolgi telah dihasilkan dengan menggunakan teknik hybridoma. Kelashubkelas immunoglobulin 9 antibodi rnonoklonal ini telah ditentukan. Daripada 5 antibodi monoklonal y ang dihasilkan terhadap P. falciparum, 1 adalah subkelas IgG dan 4 lagi subkelas IgM. Empat antibodi monoklonal terhadap P. cynomolgi adalah IgM. Sembilan antibodi monoklonal ini telah 'bertindakbalas silang' secara h a s dengan antigen-antigen trofozoit dan skizun P. fulcipurum, P. cynomolgi dan P. inui dalam ujian 'enzyme- linked immunosorbent assay' (ELIS A). Dalam 'indirect immunofluorescence test' (IFAT), kesemua antibodi monoklonal ini telah bertindak balas pada tahap berbeza hanya dengan skizon P. falciparum, P. cynomolgi dan P. inui. Tindakbalas tidak didapati dengan peringkat-peringkat bentuk cincin atau trofozoit untuk parasit-parasit Plasmodium ini.

Dalam ujian 'counter-immunoelectrophoresis' (CIE), 6 daripada antibodi-antibodi monoklonal (PF-1E4, PF-1F6, PF-1G8, PF-1H5, PC- 1E12, PC- 1A11) didapati memendakkan satu jaluran

masing-masing dengan antigen-antigen ~rofozoi t dan skizon P. falciparum, P . cynomolgi dan P. inui. Dua lagi (PF-1G8 dan PC- 1A11) telah memendakkan satu jaluran dengan antigen trofozoit dan skizon P. berghei. Analisa 'immunoblot' telah menunjukkan bahawa 4 antibodi monoklonal yang dihasilkan terhadap P. falciparum (PF-1E4, PF-1E12, PF- 1F6, PF- 1H5) mengenali epitope-epitope antigen berasingan dalam ekstrek trofozoit dan skizon P. falciparum. Satu daripada antibodi monoklonal terhadap P. falciparum (PF-1G8) dan tiga terhadap P. cyn-omnlgi (PC-1 A 1 1 , PC- 1E12, PC- 1H12) mengenali dua atau lebih epitope yang berada dalam antigen trofozoit dan skizon P. falciparum atau P. cynomolgi.

Serum imun Orang Asli yang tinggal di kawasan-kawasan endemik malaria di Semenanjung Malaysia mengenali beberapa jaluran polipeptid dalam antigen-antigen trofozoit dan skizon P. falciparum dan P. cynomolgi melalui 'immunoblotting' dan 'immunoprecipitation'. Empat polipeptid dominan dalam antigen trofozoit dan skizon P. falciparurn yang dikenali oleh serum ini mempunyai berat molekul 120, 90, 88 dan 82 kilodalton. Dalam 'immunoblot' dengan antigen P. cynomologi, serum ini bertindak balas kuat dengan polipeptid-polipeptid berat molekul 120, 105'96, 86 dan 70 kilodalton. 'In vtiro inhibition assay' yang dijalankan dengan dua isolat P. falcipurum Malaysia (Gornbak A

Page 15: IMR Bulletin Dec 1992

Tesis Doktor Falsafah

dan Gombak C) telah menunjukkan bahawa peratus penyekatan yang paling tinggi didapati pada kultur yang mengandungi ascites PF- 1G8 diikuli dengan PC- 1E 12 dan PF- 1 E 12. Antibodi-antibodi monoklonal ini bukan sahaja mengurangkan penambahan parasit tetapi menyekat perkembangan trofozoit dan skizon seperti yang ditunjukkan oleh bentuk- bentuk yang aneh di bawah mikroskopi. Epitope- epitope antigen yang dikenali oleh antibodi- antibodi monoklonal 'inhibitory' ini mungkin terlibat dalam perlindungan imun hos terhadap infeksi malaria.

Dua daripada antibodi monoklonal iaitu PF- 1G8 dan PC-1E12 boleh mengesan antigen plasmodia1 larut di dalam darah pesakit yang dijangkiti oleh P. falciparum, P. v i v a dan P. malariae dalam sandwich ELISA. Sensitiviti ELISA dengan PF-1G8 dan PC-1E12 ialah 96% dan 98% manakala spesifisiti ujian ini dengan kedua-dua antibodi monoklonal ialah 100%. Kedua-dua antibodi monoklonal ini adalah berpotensi sebagai alat seroepide- miologi bagi penyakit malaria.

Gum har Kin': Morphologi parasit Plasmodium Falciparum yang diujikan dalam asai penghambatan in vitro dengan antibodi monoklonal.

Gambar Kanan: Polipeptid antigenik PZasmodium Falciparum yang dikenali oleh antibodi dalam immunoblot.

Page 16: IMR Bulletin Dec 1992

( Kursus Diploma Teknologi Makmal Perubatan

Institut Pcnyclidikan Perubatan adalah pusat latihan bagi Teknologi Makmal Perubatan dalam Malaysia. Dalam tahun 1991 kursus Sijil dalam bidartg Teknologi Makmal Perubatan telah digantikan dengan kursus Diploma Teknologi Makmal Perubatan.

Kurikulum tersebut merupakan satu program latihan 3-tahun yang terbagi kepada 6 semester dan setiap semester akan berjalan selama 24 minggu. Ia mengandungi satu Komponen Sain Akademik, diikuti oleh latihan polivalen selama 1 112 tahun yang pertama dari diikuti olih laiihan pengkhususan bivalen pada tahun akhir. Ringkasan kurikulum tersebut adalah seperti berikut :

TAHUN 1

SEMESTER

1

(24 MWGGU)

(24 MINGGU)

POLlV ALEN

DISIPLIN

SAINS ASAS

1. Kimia Hayat

2. Anatomiffisiologi

3. Pcralatan Makmal dan Fizik

4.Statistik/Matenlatik/Asas Komputcr I 5. Genctik

6 . Imunologi

7. Pcngenalan kcpada Patologi

PENGENALAN KEI'ADA

TEKNOLOGI MAKMAL

PERUBATAN

1. Patologi Kimia

2. Mikrobiologi Perubatan

3. Parasitologi Perubatan

4. Hcmatologi

5. Pcrkhidmarin I'emindahan Darah 6. Sitologi

7. Patologi Anatomi

--

(24 MINGGU)

POLlV ALEN

TAHUN 2 SEMESTER

3 (24 MLNGG U)

POLIVALEN

TEIWOLOGI MAKMAL PERUBATAN (LANJUI'AN) 1. Patologi Kimia 2. Mikrobiologi Perubatan 3. Parasitologi Perubatan 4. Ilcmntologi 5. Perkhidmatan Pemindahan Darah 6. Sitologi 7. Patologi Anatomi

LIAN DAN KAUNSELLIhTG

DISIPLIN

LATIHAN 'FIELD' I (BUKU LOG) 1. pa to log^ Kirnia 2. Mikrobiologi Perubatan 3. Parasitologi Perubatan 4. Hematologi 5. Perkhidmatan Pemindahan Darah

6. Sitologi 7. Patologi Anatomi

TAHUN 3 SEMESTER

5

BIVALEN

DISIPLIN

LATIHAN LANJUTAN 'FIELD' KI (BUKU LOG) dalnm satu modul Pcngkhususan Bivalent berikut :- Modul 1 : Pathologi Kmia dan Pemakanan Modul 2 : Mikrobiologi dan Parasitologi Pembatan Modul3 : Hematologi dan Perkhidrna- tan Pemindahan Darah M d u l 4 : Patologi Anatomi dan Sitologi

1. Satu dari modul di atas 2. Asas Komputer I1 3. Pengumsan

I -

PEPERIKS AAN (DIPLOMA )

Program in i adalah bertujuan untuk menghasilkan JTMP terlatih yang mempunyai taraf kemahiran yang tinggi serta mampu memberikan perkhidmatan makmal yang bermutu tinggi. Serarnai 120 orang pelatih dijangka memulakan kursus ini pada bulan Nobember tiap-tiap tahun.

Page 17: IMR Bulletin Dec 1992

Sdn l z sntrc Frcngsi IMR

/ Bahagian Ternakan dan Penyelidikan Haiwan Makmal, IMR.

Haiwan Makmal rnerupakan konlpol~rn yang tidak daprtt dipisahkan dari institusi penyelidekan perubatan. Haiwan-haiwan ini selalunya digunakan sebagai model until k kajian patogenisis peny aki t atail kemoterapi serta dalnr;; diagnosa pen yakit beriongkit.

Penubuhan Bahagian Ternakan d;in Penyelidikan Haiwan Maknial atau Rumah Haiwan boleh dikesan dari sejarah penubuhan Institusi ini. Ia telah ditubuhkan dengan ti$;( objektif. Pertama untirk pengelunr-an haiwan makmal yang akan digunakan dalam penyelidikan dan diagnosa, kedua untuk mcnyedinkan pcrkhidmntnn veterinar dari scgi nasihat serta bantuan tekniknl kepada para penyelidek yang mengg~~nakan haiwnn makuta1

Gnrnbrrr 2 - Tiktrs llzrde berbrritding dengm tiklrs bicrscr

Ruat masa ini terdapat s ep~~ loh spesis haiwan mxkrnal yang di y e l i t ~ ~ a di Bahagian ini. Ini

ternmuk mencit, tikus. arnab, argus, monyet, angsa, bebisi sertii kancil. Haiwan terbaharu yang telah besjaya d~bi;ik ialah sejenis haiwan biak khas iaitu tikus mutan (tikus nude) yang telah diasaskan pada t:lhun 1991. Tikus 'specific pathogen free' ini dipelihira dalrm isolator- untuk mernastikan penghidupannya. Anggarrtn 25,000 hingga 30,000 haiwan mnkrnal di bekalkan setahun ilntuk memenuhi permintam para penyelidek bukan sahaja dari IMR mnlnh i j:lb:itan-j:ih:ltan l a i n

Kementerian Kesihatan dan kadangkala p i h k universiti.

dalam penyelidikan niereka dan ketiga untuk menjrtlani penyelidikan.

Pengurusan haiwan-haiwan ini nierangkumi tiga rzspek iaitu peruniahan, pemrtkanan serta kebersihan. Pada asasrlya haiwan-haiwan i n i

Page 18: IMR Bulletin Dec 1992

Salalt satu Fungsi IMR

dilctak dalam sangkar yang tclah dialas dengan habok papan yang sudah di otoklav. Sangkar- sangkar ini kemudian di tingkatkan dalam rak untuk penjimatan ruang. Rak-rak ini kemudian ditempatkan dalam bilek yang menggunakan pengaliran udara biasa. Makanan haiwan- haiwan ini terdiri daripada untilan yang dibuat oleh pengilang tempatan dan beserta dengan air, diberi secara ad libitum kepada haiwan-haiwan tersebut. Sayuran juga turut diberi kepada argus dan monyet. Kebersihan merupakan aspek yang penting dalanl memastikan keadaan uenvakit minima d i c a ~ a i n~elalui suatu rutin 1 d

pencucian dan disinfeksi.

Perkhidmatan veterinar yang merupakan salah satu dari fungsi Bahagian ini diberi kepada para penyelidek yang memintanya. Perkhidmatan yang diberi termasuk rawatan, bedah siasat, pengambilan darah, pembedahan serta nasihat mengenai pengurusan haiwan tersebnt dari segi penyakit serta pelalian. Dengan berjalannya jawatankuasa penggunaan dan penjagaan

Gambar 3 - Isolator uittuk persekitararz steril

haiwan makmal, dimana semua cadangan projek yang akan menggunakan haiwan makmal hendaklah mendapatkan kelulusan dari jawatankuasa ini maka aspek perkhidmatan iniakan dipertingkatkan.

Disebabkan penekanan semasa terhadap pentingnya penggunaan haiwan makmal yang

Ganzbar 4 - Hamster

berkualiti dalam penyelidikan maka Bahagian ini telah berusaha untuk meninggikan lagi tahap pengurusan di Bahagian ini. Satu survey yang telah di lakukan oleh Bahagian ini untuk menentukan tahap penggurusan di Rumah Haiwan yang lain telah menunjukkan bahawa aspek kualiti kontrol sangat berkurangan menghasilkan haiwan yang tidak bermutu. Oleh

Gambar 5 - Arnab

kerana terdapat banyak penukaran haiwan makmal diantara rumah-rumah haiwan maka usaha sedang di lakukakan untuk menstandardkan cara-cara pengurusan. Dengan keadaan kekurangan dari segi tenaga pekerja serta peruri~ukkarl aclalah diharap usaha ini akan menghasilkan kualiti haiwan yang lebih baik untuk penyelidikan.

Page 19: IMR Bulletin Dec 1992

Krcrszrs h i t Bengkel

Kursus Latihan 'l'eknikal SEAMIC dalam Penyakit Gastrousus

K u r s u s Latihan Teknikal SEAMlC tentang Penyakit Gastrousus telah diadakan di Institut Penyelidikan Perubatan Kuala Lumpur prtda 27-31 Januari 1992. Kursus ini telah ditaja oleh Pusat Maklumat Perubatan Asia Tenggaral Yayasan Perubatan Antarabangsa Jepun (SEAMICIIMFJ), dengan kerjasama Kementerian Kesihatan Malaysia.

Matlamat Kursus ialah untuk memper- t ingkatkan pengetahuan dan kemahiran mengesan patogen enterik dan juga mernperluas pengetahuan tentang perkembangan terkini dalam penyakit ga~t rmsus .

17.. 11uliah dan praktikal makmal Kursus

diltendalikan oleh dua orang Koordinator/ Pensyarah SEAMIC, Prof Dr Hideo Hayashi dari Universiti Tsukuba d m Prof Dr Takeshi Honda dari Institut Penyelidikan Penyakit Mikrob, Universiti Osaka. Dr Narimah Awin dari Kementerian Kesihatan Malaysia juga diundang untuk memberi kuliah bertajuk Epiderniologi Bakteria Enterik di Malaysia. Sembilan orang pesel-ta, empat dari universiti tempatan, tiga dari hospital dan dua dari IMR telah nlenghadiri Kursus ini.

Kandungan Kursus meliputi aspek kevirulenan bakteria dan kaedah-kaedah mengesan faktor- fnktor virulen, termasuk pcnggunaan prob gen

dan Tindakbalas Rantaian Polymerase (PCR) . Tumpuan diberikan kepada faktor-faktor virulen Escherichia coli, Vibrio clzolerae dan Vibrio paruhuernolyticns berserta kaedah- kaedah mengesan hemolisisn dan enterotoksin yang dikeluarkan oleh bakteria tersebut.

Di samping kaedah biasa, peserta diperkenalkan dan diberikan peluang mendapatkan pengalaman langsung menggunakan kit ujim komersial, 'reversed passive latex agglutinarion' dan asai imuno ELISA untuk mengesan hemolisin dan enterotoksin. Peserta juga berpeluang menggunakan prob gen dalam hibridasosi koloni bagi E. coli enterotoksigenik.

Dalam majlis penutup yang ringkas, sijil-sijil Kursus disampaikan oleh Y. Bhg. Tan Sr i Dato' Dr Abu Bakar Dato' Suleiman, Ketua Pengarah Kesihatan Malaysia yang juga Pengerusi Jawatankuasa Penyelerasan SEAMIC.

Surnhangun Cheong Yuet Meng

Bengkel Kebangsaan Kepastian Kualiti bagi Program Perkhidmatan Makmal

P r o g r a m Kepastian Kualit i (PKK) Kementerian Kesihatan Malaysia (KKM) merangkumi beberapa bidang tertentu termasuk

Page 20: IMR Bulletin Dec 1992

Perkhidniatari Maknial. Institut Penyelidikan Perubatan dilantik sebagai Sekretariat PKK bagi Perkhidmat Makmal ini. Jawatankuasa induk Program in1 dltubuhkan pada September 1990 dan ahlinya terdiri daripada pegawai- pegawai yang terlibat secara langsung dalam pengurusan makmal, iaitu pakar kajipenyakit, pegawai sains d m teknologis serta beberap orang klinisian yang mewakili pengguna perkhidmatan makmril.

Dalam usaha menyelaraskan aktiviti, pada 3 - 4

Disember 1991, Bengkel Kebangsaan Kepastian Kualiti bagi Perkhidmatan Makmal tclah diadakan dan dihrtdiri oleh 90 orang peserta. Objektif utarna bengkel adalah untuk menerangkan dan niembincangkan konsep PKK, serta membincangkan aktivlti d m perkembangan program Perkhidmatan M;zkmd. Beberapa kertas kerja telah di bentangkan. Empat jawatankuasa kecil, iaitu jawatankuasa patologi kimia, mikrobiologi perubatan, kaj idarah dan penabungan darah, dan histopatologi dan sitologi turut ditubuhkan. J awa tankuasa - j awa ta~~k~l~ i sa ini menibin- cangkan indikator pencapaian analisis dan 'turn-around-time' bagi ujian-ujian yang dikenalpasti dalam disiplin masing-masiug. Enam indikator dikenalpasti untuk dikaji dengan teliti dalam proj-ek pilot awal 1992.

Kursus Epidemiologi Tropika Asia Keli ma

Kursus Epidemiologi Tropika Asia Kelirna anjuran Institut Penyelidikan Perubatan, Kuala Lumpur telah diadakan di Hotel Asia, Kuala Lumpur dari 18 Oktober 1991 hingga 15 November 199 1.

Kursus ini dibiayai oleh SEAMEO- TROPMED Serantau, Agensi Kerjasama Teknikal Jerman (GTZ), dan Dana Bantuan Teknikal Pakar Australia. Seramai 42 peserta kursus terdiri daripada doktor perubatan, pergigian dan haiwan, d m saintis dari Thailand, Filipina, Indonesia dan Malaysia. Tenaga pengajar pula dari Australia, Kanada, Indonesia, Filipina, Thailand d m Malaysia. Program kursus meliputi syarahan tentang prinsip epidemiologi d m biostatistik, menginterpretasi data rnelalui kertas kritikan, latihan praktikal dan lawatan ke pusat kesihatan dun hospital daerah di Srlangor. Kursus ini juga mendedahkan peserta kepada pengalaman praktikal penggunaan program komputer dalarn epidemiologi. Latihan juga ditumpukun kepada pelbagai masalah penyelidikan, reka bentuk penyelidikan d m penyediaan proposal penyelidikan.

Sutnbangan Lye Munn Sann

Bengkel Kebnngsnnn Kepastiait Kualiti bagi Prograin Perkhidinntan AIaRrnal

Page 21: IMR Bulletin Dec 1992

A iitibiotik

Pengawasan Keresistanan Antibiotik Kebangsaan 1992

Sernenjak 198 1. Bahagian Kajikunian IPP telah menerbitkan maklumat corak kepekaan antibiotik bagi pencilan bektiria Klinikal dalam Buletin ini untuk menafaat doktor-doktor. Walau bagai~nanapun data yang ditei-bitkan pada masa lalu adalah daripada beberapa buah hospital yang mendapat bsntuan perkhidmatan IPP.

Di Bengkel pertama Ahli Kajikunian Hospital yang diadakan pada bulan September 1987 telah diputuskan bahawa data ini haruslah lebih menyeluruh dan langkah ini diteruskan sebagai Program Pengawasan Keresistanan Antigiotik Kebangsaan. Semua hospital-hospital besar berset~iju menghantarkan data mereka ke IPP, dan ringkasan maklumat keseluruhan yang diterima ini akan diterbitkan di dalam Buletin IPP dengan itu bertcrusan memainkan pernnnn sebagai bank data mengawasi aliran corak keresistanan antibiotik bagi pencilan-pencilan yang biasa terdapat di negara ini.

Jadual I menunjukkan kadar keresistanan semua bakteria yang diasingkan kepnda

beberapa antibiotik yang diuji di 15 buah nlakrnal dalam bulan a g o s dan Septemher sahaja. Jadual 2. menunjukkan keresistanan bakteria tertentu kepada antibiotik sepanjang taliun kerana ciri-ciri serperti ini tidak sclalu berlaku. Apabila keresistanan seperti ini dikesan makmal-makmal berkenaan dikehendaki menghantar kultur ini ke IPP untuk disah dan dikenalpasti. Tetapi malangnya makmal-makmal berkenaan gaga1 berbuat demikian, oleh itu lapuran nlengenai keresistanan Neisseria gonorrhoeae terhadrtp spectinomycin, penicillin d m MRSA yang 'resistant' kepada vancon~ycin mungkin tidak seperti yang digambarkan. Kesilapan seperti ini merupakan 'teknikal' sa hnja oli h kernna makmal yang terlibac mengenalpasti kuman yang tidak tepat atau menggunakan konsentrasi antibiotik yang tidak betul. Langknh-lnngknh yang perlu telah pun diambil untuk mengurangkan kesilapan seperti ini. Pada keseluruhannya didapati corak. keresisranan ar~libivlik ~ i d a k banyak berubah berbanding tahun-tahun lepas.

Sumhangan Cheong Yuet Mcng

Page 22: IMR Bulletin Dec 1992

Jadrial I : Pengawasan Kebangsaan Keresistanan Antibiotik (Ogos-Sep 1992) Peratus Organisma Resistan terhadap A ntibiotik -

C

I Acinetobacter 22.4 79.9 25.8 33.3 51.3 30.8 23.2 49.1 84.3 86.4 5C (911) (1148) (434 (21) (692) (708) (893) (1088) (695) (103) (1 1

Cilrubucrer spp 7.1 76.6 25.8 75.0 15.2 (15.7) 15.7) 25.7 52.8 16.7 3$ (112) (158) (31) (4) (79) (70) (121) (144) (72) (6) (I!

Enterobacter spp 9.7 80.8 22.2 34.8 18.5 18.4 20.4 25.7 67.1 22.8 3C (413) (647) (180) (23) (383) (293) (411) (571) (298) (57) (5:

Esherichia coli 5.9 62.9 9.7 59.6 17.9 . 6.7 7.0 7.7 20.9 28.4 4C

(1910) (2626) (575) (41) (1509) (1541) (2007) (2597) (1566) (331) (27 Morganella 0.0 75.0 0.0 28.6 9.7 6.1 4.3 38.6 67.6 33.3 31 morgunii (44) (64) (15) (7) (31) (33) (46) (57) (34j (15) (6 Proteus spp 3.7 51.3 2.3 20.8 12.5 5.9 3.8 14.5 32.0 50.0 4 1

(43.5) (677) (130) (24) (328) (373) (477) (594) (387) (46) (6 - Pseudomonas 6.5 9.7 35.9 16.5 20.8 6.3 aeruginosa (1454) (423) (702) (1078) (674) (1433) Pseudomonas spp 23.6 21.8 62.2 20.8 30.3 8.6 70.3 2:

(4 19) (156) (135) 289) (211) (465) (64) (' Salmonella spp 3.9 9.8 5

(230) (224) (2 Salmonella Typhi 9.4 9.1 9

( 180) (175) (1 Shigella spp 55.2 46.4 31

(29) (28) (2 Serruiiu spp 11.4 86.3 0.0 15.4 14.3 46.9 70.1 2.

(44) (51) (19) (39) (42) (49) (37) (52) Staphylococcus 19.1 7.6 2' aurcus (309) (185) (2: I MRSA 68.1 7.1 7'

epidermidis (15) (45) (1 Coagulase 15.0 2 negative Staph. (100) (2 Group A Streptococcus - Group B Streptococcus Srreptococcus 0.0 1.6 2

I No. - % of Resistance (No.) - Total no. tested ag

Page 23: IMR Bulletin Dec 1992

Tuble I : National Surveillance of Antibiotic Resistance (August-September 1992) Percentage o f Or~anisms Resistant to Antibiotics

s t thc antibiotic * - not confirmed

31

Page 24: IMR Bulletin Dec 1992

Jadual II - Survei Kerentanan Antibiotik Kebangsaan bagi Bakteria Spesifik (Jan-Dis 1992) : % Keresistanan

Hospital

Organisms Perlis A.Setar Penang Ipoh K.Bahru KTerengganu Kuantan

S.aureus 9.8 18.0 18.4 27.9 11.0 21.8 44.0

(MRSA) (235) (121 1) (1 6 10) (2460) (1 15 1) (1750) (546)

N.gonorrhoeae 0.0 38.5 34.1 18.8 48.0 0 .O 33.3

(PPNG) (4) (3% (20-5) (16) ('29) (1) (3)

N.gonorrhoeae 0.0 0.0 0.0 0.0 0.0

(Spectinomycin R) (39) (203 (16) (29) (1)

H.in.uenzue 0.0 5.3 0.0 0.0 0.0 0.0 0.0

(Chloramphenicol R) (0) (19) (2) (126) (5) (10) (5)

Hhfluenzae 0.0 5.3 0.0 0.0 0.0 0.0 0.0 (Ampicillin R) (0) (19) (2) (126) (10) (10) (5)

4

S.pneumoniae 0.0 0.0 0.0 8.6* 0.0 0.0 0.0

(Penicillin R (1 1) (24) (25) (50) (10) (22) (9) & relatively R)

S.Typhi 0.0 0.0 3.6 10.3 0.1 0.0 0.0

(Chloramphenicol R) (3) (72) (28) (97) (749) (58) (10)

V.cholerae

(Tetracycline R)

Grp. A Strepr

(Penicillin R)

Grp. B Strept (Penicillin R)

* : Not confirmed No.

Page 25: IMR Bulletin Dec 1992

Hospital Kelang K.Lumpur Scrcmban Mclaka J.Bahru KKinabalu Kuching IMR All Hospital

20.5 29.8 22.2 9.5 43.3 2.5 6.8 21.1 (2 1 10) (4657) (895) (1420) (1 113) (2086) ( 1249) (22529)

Table II - National Antibiotic Susceptibility Survey On Specific Bacteria (Jan-Dee 1992) : % of Resistance

1

s -

-

-

-

-

-

-

-

-

- : % of resistance ( 1 : total no. tcsted

Page 26: IMR Bulletin Dec 1992

Antibiotic

Antibiotic Resistance Surveillance Programme 1992

Since 198 1, the Division of Bacteriology, IMR has been publishing the antibiotic sensitivity patterns of clinical bacterial isolates in this bulletin for the benafit of doctors. Unfortunately, the data published in the past has been that of a few district hospitals served by the IMR.

At the First National Meeting of Hospital bacteriologists hcld in Scptembcr 1987, it was decided that the data should be more comprehensive and take the form of a National Antibiotic ~esistance' Surveillance Programme. All general hospitals agreed to send their data to the IMR and the total information received would be published in this Bulletin. The IMR has thus assumed the role of a data bank monitoring emerging trends in antibiotic resistance amongst the common isolates in the country.

Table I shows the resistance rate of all bacteria

to various antibiotics tested in the 15 laboratories for the months of August and September only. Table I1 shows the resistance of specific bacteria to specific antibiotics throughout the year as the occurrences of these are rare. When such resistance wera detected the laboratories concerned was required to send the strains to IMR for cornfirmation. Unfortunately this had not been done all the time and therefore the report on spectinomycin resistant Neisseria gonorrhoeae, penicillin resistant Group A and B saeptococci and the vancomycin resistant MRSA may not be true. These are most probably technical errors as those laboratories that did submit such 'resistant' strains were shown to have either identified them wrongly or used the wrong antibiotic disc strength. Continuous effort has been made to rninirnise such errors, On the whole there has not been much changes in the resistance pattern of the various organisms compared to previous years.

Page 27: IMR Bulletin Dec 1992

Idending Article

Mosquitoes are found in the rural and urban areas of Malaysia. They are responsible for the transmission of malaria, dengue, filariasis and Japanese encephalitis. Besides being a danger to health, mosquitoes are annoying and can cause sleepless nights.

Vector control measures include indoor residual spraying of DDT as (the principal anti- malarial measure), space-spraying such as ULV spraying and thermal fogging of malathion (during outbreaks of dengue, Japanese encephalitis and malaria cases), and larviciding with malathion and Abate. However these measures are inadequate owing to operational and other constraints. In recent years environmental consequences of con trolling mosquitoes with insecticidal spraying have been questioned. Thus some alternative approache< nf protecting man

against mosquito bites are being given priority.

There is a growing awareness of the need for inexpensive self-help type of control strategies which can be used at the con~n~unity level. Several self-protection techniques du exist and these, if used consistently, can greatly reduce man-mosquito contact and, in some cases, greatly reduce the mosquito population. The method of self-protection depends on the circumstance. Application of repellents on clothing or skin is the best method for outdoor protection.

DEET (di-ethyl toluamide, a common chemical repellent) and pyrethroids (like

deltamethrin and permethrin), when used for impregnating jackets, anklets, wristbands and headbands have been found to be effective against the local mosquito vectors, as shown by studies carried out in the IMR. DEET and other repellents can also be applied to the skin (especially around the neck, anklesand wrists) for extra protection. There are at least ten different brands of topical rcpcllcnts in the Malaysian market but not all are as effective as claitiied by the companies marketing them,

Mosbar, a new repellent formula from Australia containing permethrin and DEET, was evaluated for its repellent and insecticidal properties against Malaysian mosquito vectors and nuisance mosquitoes and it has been found to be inexpensive, long lasting (up to 8 hours after application), and effective.

Mosquito coils, vaporising mats and household aerosols have been shown to work indours and there are widely available in Malaysia. The active ingredient used in most household insecticide products available is synthetic pyrethroids, except for a few brarids which use a combination of carbamate and/or organophosphorus. Vaporising mats (10 brands of which sold in Malaysia) have limited application as they must be inserted into a small heater to release the repellent vapor. Mosquito coils (15 brands available) also produce a vapor to repel moscluitoes. Space spraying with ho~rsehold aerosols (at least 15 brands), usually contain synthetic pyrethroids which kill mosquitoes in the area. The sound producing

Page 28: IMR Bulletin Dec 1992

devices/buzzers have been shown to he ineffective in repelling nioscluitoes both in the laboratory as well as in the field.

The prevention of contact between man and the mosquito vectors is important especially at night when one is ablccp. Bednets have long been used for this purpose but it is only recently that they have been impregnated with an effective insectic~de that kills the mosquitoes as well as fends them off. In fact this cheap and simple tool is attracting increasing interest as a key intervention measure against transmission of mosquito-borne p:irasites.

In 1990, a study was initiated by 1MR to determine the impact of permethrin impregnated hednets o n the vector density and malaria occurrence in a n Orang Asli community in Pahang, PeninsuJar Malaysia. Surveys carried out at thc start of thc study (199011991) to assess the relationship between malaria incidence and the use of bednets among the locals indicated that usage of bednets provided significant protection against malaria. Malaria infections per person-month at risk

were lower anlong bednet users. Post-control results obtained after the distribution of the permethrin impregnated bednets showed a significant drop in the number of malaria cases as well as in mosquito sporozoite inoculation rates in the study area.

This trial and other smaller scale trials in Malaysia as well as in other countries have provided clear e v ~ d e n c e that bed nets impregnated with synthetic pyrethroids can significantly reduce contact with malaria transmitting mosquitoes and thus reduce the incidence of the infection. Similarly, impregnated curtains that cover eaves, doors and windows have been shown to reduce mosquito bite indoors, although they may be less effective than bednets.

Additional individual measures to reduce human-mosquito contact include housing improvements such as installation of window and door screens, the replacement of rattan and bamboo by more solid material for walls and floors, and housing site selection i.e. away from mosquito breeding areas.

A Dot-Immunobinding Assay for 1 detection of Rickettsia tsutsugamushi in

Rickettsia tsi~tsuyamusl~i is the organism that mites. The 3 vector species found in Peninsular causes the disease, scrub typhus. Scrub typhus Malaysia are Leptotromhidium deliense, is endemic in Southeast Asia and is transmitted Leptotromhidium fletcheri and Leptotrom- by the bite of chiggers, the larvae of certain hid i~~m nrenicolu. These vectors are known to

Page 29: IMR Bulletin Dec 1992

Diagnosis

exist in nature as two distinct populations, one population is able to transmit the disease while the other is unable to, In order assess the risk of scrub typhus in an area, it is important to determine whether the chiggers present in the area are infected with the rickettsiae.

Traditionally the detection of scrub typhus infection in chiggers is through isolation in animal hosts and the direct fluorescent antibody technique (DFAT). The former is time- consuming while the latter requires an expensive fluorescence microscope as well as expertise in interpretation. Both these techniques are not suitable for use in the field.

A Dot-Immunobinding Assay (DIBA) which dues uut have the d i d v a r ~ ~ a g e s uf L ~ K LWU

rechniq~ies discussed above has recently been developed. The technique is illustrated in hgure 2. Indiv~dual chigger extracts are first dotted on to cellulose acetate filter paper discs. The discs are dried ovefnight and then soaked in a 5% skim milk solution for 1 hour. The skim milk acts to block surface area of the paper discs which are not coated with the chigger extracts. The skim milk solution is removed and hyperimmune serum from rabb$ immunized with the R. tsimugnmushi is added.

After incubation for 2 hours, the antiserum is removed and the discs washed with a Tris balanced saline (TBS) buffer. Goat anti-rabbit immunoglobulins proxidase conjugare is then added. After 2 hours of incubation, the discs are again washed with TBS buffer. A subtrate solution of diatninobenzidine tetrahydro- chloride is added. After 30 minutes incubation, the subtrate solution is removed and the discs dried overnight. Discs containing extracts of positive chiggers will display a brownish spot while those with negative chigger extracts will not (Figure 1).

The DIBA has two distinct advantages over the other two techniques. It can be used easily in the field and the results can be kept as a ~ C I I I ~ I ~ ~ X L I c c u ~ d f o ~ ~LI~UI-e references. A prototype kit, for use by vector conrrol officers who do not have the benefit of laboratory Pdcilities, is being developed. The UlBA in lts present form is unable to differentiate between the various strains of R. tsutsugamushi. It usefulness is as a preliminary screening technique for scrub typhus infection in chiggers. The strains of R . tsutsu~amushi can then be identified by the DFAT.

Figure 1: Results of dot-immunobinding assay A - row of negative discs, B - row of positive discs

Page 30: IMR Bulletin Dec 1992

Spot exudate (A) onto disc

nry overnight

lncubate with blocking solution (l)

Remove blocking solution

lncubate with rabbit antiserum (n)

Wash with buffer

E

Incubate with peroxidase conjugate ( &E)

Wash with buffer

lncubate with substrate (

Remove substrute and air - dry

Check for b r w n spot on disc

Figure 2: Procedure for Dot-irnnzunobinding assay

Page 31: IMR Bulletin Dec 1992

Research

Acute Respiratory Tract $nfection in children: a community-based

A longitudinal community- based study, with the ultimate aim of reducing severe Acute Respiratory Infection (ART) in children, was conducted in Kelantan to evaluate the impact of 2 interventions, namely educating mothers to recognise in their chiIdren signs and symptoms of ARI that require medical attention, and training of hospital and health staf f in case management by the consultant paediatrician.

Pnsir Mas district was selected as the intervention area, while the sociodemo- graphically similar districts of Machang and Pasir Puteh served as the control areas. Twenty-five villages were selected randomly in each area. A total of 4,378 children below 7 years of age were followed up every 2 weeks in a house-to-house survey over a one-year period. Over the same period, a total of 1 1,483 cases of ARI seeking treatment at &strict hospitals, health centres and midwife clinics (klinik desa) were reviewed in terms of severity of infection and case management.

During the survey 4,460 and 4,238 ARI episodes were detected in the intervention and control areas respectively, giving an overall annual incidcncc of 1.98 cpisodes pcr child. The incidence in the intervention area was 1.9 episodes per child (4460/2406) and 2.1 (42381 1972) in the control area. 34% of children had one episode, 21 % had two episodes while 45% had 3 or more episodes of ARI. The majority (42%) of episodes lasted 2-3 days. No seasonal

variation in ARI incidence was detected in the two areas. 97% of episodes were mild, 1% moderate and 2% severe. These proportions were similar in the two study areas.

When a comparison was made between the the proportion of severe episodes in the first 2 months and in the last 2 months of the study, there was a much greater reduction of severe ARI cases (62.7%) in the intervention area then in the control area (15.4%) p.cO.01). In

addition, there was a continuing decrease of severe ARI during the study period in the inlerventiori area bat 1101 in the conlrol area.

Of the 11,483 episodes of ARI from the intervention and control areas treated at government health centres, district hospitals and the Kota Baru General Hospital, 65% were mild, 32% moderate and 3% severe. In the intervention area, 10% of mild ARI were given antibiotics, compared with 25% in the control area. There was less inappropriate antibiotic use in the intervention area compared to the control area. These. results have important implications for an ARI control programme in Malaysia.

This study was carried out by:

Lye M S , Uma Devi, Lai PFK, Hanjeet Kaur, Choo KE, Azmi Shapie, Azmi Hashim, Wan Mansor H , Fatimah D,

Chang CY, Nor Azmi, Thevaraj S, Abdul Aziz Mahmud,

Jit Singh, Laila Noor, Azizan Aiyub Ghazali and Anuar Bachee.

Page 32: IMR Bulletin Dec 1992

The Immunization Programme

Immuniza t ion remains one of the most powerful and cost-effective tools for the control of infectious diseases. Recognizing the importance of immunization, the World Health Organization (WHO) initiated the Expanded Programme of Immunization (EPI) in 1974. The objective of EPI is to reduce morbidity, mortality and disability from six main diseases, viz. diphtheria, pertussis, childhood tetanus including tetanus neonatorium, poliomyelitis, measles and childhood tuberculosis, by providing infants and women of child-bearing age with the required vaccines.

In Malaysia, routine immunization is available for the six childhood diseases. Rubella immunization was introduced in 1988 and Hepatitis B vaccination was introduced as part of the childhood immunization programme in 1989 (see next page). An important feature of the programme is that it is provided free in government clinics and hospitals. However immunization has not been made compulsory by law.

The Immunization Programme is co-ordinated and supervised at the national level by the Hcalth Division of the Ministry of IIealth. The Maternal and Child Health Unit co-ordinates and supervises the operational aspects while the Epidemiology Unit is involved in programme evaluation, vaccine control and potency evaluation in collaboration with the Institute for Medical Research. The purchase, storage and distribution of vaccines is controlled by the Central Medical Store of the Ministry of Health. The impact of our national programme can be

observed from the dramatic reduction of disease incidence and from the coverage. The incidence of these diseases has declined significantly since the implementation of routine immunization services in the early 1970's. Reported cases of diphtheria has declined from 230 in 1976 to 9 cases with 1 death in 1990; whooping cough has declined from about 300 cases in 1976 to 24 in 1990. Tetanus neonatorium cases has been declining to a range between 15 to 20 cases annually. There has been no reported cases of poliomyelitis since 1986.

In accordance with the objectives of achieving Universal Child Immunisation (UCI) in 1990, various strategies were launched in 1989 to intensify the implementation of EPI in Malaysia. This has resulted in an impressive improvement in immunization coverage from 72 percent in 1988 to the achievement of the UCI goal of 80 percent coverage by Triple and Polio immunization. Measles immunization coverage has not reached 80 percent. Cases of measles still remain between 2000 and 5000 annually. To remedy this situation a new schedule requiring measles immunization by the firbt birthday was i~l t~uduced in 1991.

The Ministry of Health has carried out various projects to review and evaluate EPl in Malaysia. A community serosurvey was carried out by the IMR and Universiti Sains Malaysia in late 1990 in Kelantan. Malaysia will continue to intensify efforts to accelerate immunization activities in order to achieve the WHO goal of 'Health for All by the Year 2000'.

Page 33: IMR Bulletin Dec 1992

IMR Publications

H i ~ t o r y of In?iu~nizntinn in Malaysia

1. Smallpox Implemented in 1950 and discontinued in 1980

2. D.T. (Diphtheria & Tetanus) Implemented in 1955.

3. D.P.T. (Diphtheria, Pertussis & Tetanus) Introduced in 1958.

4. B.C.G. Introduced in 1962.

5. Poliomyelitis Introduced in 1972 after an epidemic.

6. Tetanus toxoid (for pregnant mothers) In traduced in 1974.

7. Measles Introduced in 1982.

8. Rubella Introduced in 1988.

9. Hepatitis B Introduced in 1989.

Abstracts of IMR Publications

Evaluation of suppression of growth hormone levels following a 75g Oral Glucose Tolerance Test.

Wan Nazaimoon Wan Malzmod, ML Nx, N Satgunasingain and Khalid Kadir

T h e objective of this study is to use in-house radioimmunoassay (RIA) to test thc specificity of oral glucose tolerance test (OGTT) to suppress growth hormone (GH) levels at 1-hour and 2-hour in normal subjects and in impaired glucose tolerance (IGT), diabetic (IDDM) and

acromegalic patients. In addition, this study also aimed at establishing the cut-off GH value during OGTT based on the in-house assay. From the results, i t was found that nadir GH levels at 2-hour post-OGTT in normal subjects ranged from 0.4 to 8.4 mIU/L with 95% confidence interval being 0.4-4.4TU/L. In IGT and IDDM patients, basal fasting GH levels were not significantly different from normal and did not alter during OGIT. In contrast, acromegalic patients had elevated fasting GI1 levels (11.8-178 mIU/L) which were not suppressable by glucose. Hence this study clearly showed that confirmatory diagnosis of acromegaly should be made only after OGTT.

Page 34: IMR Bulletin Dec 1992

Post-menopausal smear patterns - a review of vaginal smears 480 women.

B Pillay, SK Yap and GL Lim

Med J Malaysia 1992; 47: 38-43

Th i s project was undertaken to determine the cytohormonal patterns in normal, asymptomatic postmenopausal women. 480 vaginal smears from these women, their ages ranging 36-74 years, were assessed for cytohormonal patterns from VCE smears submitted for routine cervical cancer screening. 50% showed atrophic smears consistent with total oestrogen lack. 41 9% had mild to moderately proliferative s~iiears compatible with suboptimal oestrogen stimulus. 9% had highly proliferative patterns characteristic of unopposed oestrogen effect and in this group one endometrial hyperplasia and one adenocarcinoma-in-situ were identified. This study shows that the hormonal status of the post menopausal woman is not dependent on the agepr duration of menopause. Cytohormonal evaluation is useful in selecting women for hormonal replacement therr-lpy and identifying the women at risk for endometrial pathology.

Effect of combined law-dose oral contraceptives on blood viscosity and haematocrit

Roshidah Ishak, CK Loh, Khalid Hassan and Henry R Gudurn

Malaysian J Reprod Hlth 1991; 9 ( l ) : 5-8

A cross-sectional study examining the effect of combined low-dose oral contraceptives (OC) on haernatocrit and blood viscosity was carried out involving 43 womcn, 27 OC us r s ard 16 non- OC users, acting as controls. OC users were divided into 2 groups, group 1 consisting of 16 women taking OC containing 30ug ethinyloestradiol + 150ug desogestrel daily for a period of one year or more, and group 2

consisting of 11 women on OC containing 30ug ethinyloestradiol + 150ug levonorgestrel daily for the same duration. There was significant increase in the haematocrit (p<0.001) and blood viscosity ( ~ ~ 0 . 0 5 ) of subjects on OC containing Ievonorgestrel (as the progestrogen) but no similar effect was observed in women taking OC containing desogestrel (as the progestrogen) in the preparation of the combined low-dose OC investigated in this study. The findings indicate the need to monitor women long-term on OC in order to develop appropriate indicators, on which the decision to discontinue OC, owing to increased thrombotic risk, can be based.

Alpha-1-antitrypsin deficiency in babies with prolonged jaundice.

Zakiah Ismail, M o k d Zaini Abd Rahman, Jamilah Baknr awi Zawiah Ahrnad

Malaysian J Path01 1992; 14(2): 91-4

Ove r a rhnt. year period, we randomly studied 3 10 babies with prolonged jaundice admitted to the General Hospital, Kuala Lumpur. The main objective of the study was to determine the incidence of Alpha-1-antitrypsin deficiency in these babies as it is known that Alpha-l- antitrypsin deficient babies can present with prolonged jaundice in early life. Ninety-two babies (29.7%) was found to be Alpha-l- antitrypsin deficient. The percentage incidence was highest in Indians (33.3%), followed by Malays (3 1.9%) and Chinese (26.7%). There was also male preponderance with M:F ratio of 1.6:l. Most of these babies presented at the hospital were between two weeks arid orit.

month old. Apart from the problem of prolonged jaundice and Alpha- 1-antitrypsin deficiency, 2 had associated bleeding problems, 11 had associated infections and 3 had respiratory problems. Two babies had clinical features of Down's syndrome and 2 had G6PD deficiency. AST, ALT and ALP04 were high in 20, 26 and 3 babies respectively.

Page 35: IMR Bulletin Dec 1992

Ph. D. Thesis

Clinical Applications of Human Growth Hormone Measurements

(Abstract of thesis submitted in 1991 to Universiti Kebangsaan Malaysia by Wan Nazaimoon bte Wan Mahmod for the degree of Doctor of Philosophy)

Endocrine hypothalamic-pituitaly functions can be assessed by either basal or dynamic stimulation/suppression test and measurements of pituitary peptide hormones such as growth hormone (GH) and prolactin (PRL). Measurements of serum GH levels is the most commonly used method to confirm diagnosis of GH deficiency causing short stature and excess GH in acromegaly. In-house radioimmunoassay (RIA) and enzyme immunoassay (ELISA) for GH, and RIA for PRL were developed by the production of primary and secondary, highly specific polycIonal antibodies. Validity and reliability of these in-house assays were proven by recovery, linearity and reproducibility studies.

Basal fasting GH (FGH) levels in the normal population were found to be sex- and age- dependent. During pre-puberty, girls had significantly higher FGH levels than boys (p<0.05). This sex difference was no longer apparent for pubertal children and adults. Whilst the overall FGH levels in all of the normal children of Tanner stage 1 to 4 were found to be signiikantly correlated to their heights (r=0.304, p<0.001), FGH levels in the boys alone, showed significant correlation to testosterone levels (r=0.358, p=0.006).

In both sexes, FGH levels were found to be highest in children of Tanner stage 2 to 4 and in young adults, then declined, and remained low

thereafter with advancing age (pc0.001). Hence, the normal reference ranges establishrd for FGH were according to sex and Tanner staging in pre-pubertal and pubertal children respectively, and according to age in adults.

Reference ranges far fasting growth hormo- ne levels in rtorinal adults.

l Pre~utertal Males Females

Pubertal Tanner 2,3,4 'l'anner 5

Adults 21 - 44 years 45 - 81 years

-1 -

95 % Confidence interval

The clinical usefulness of physiological stimulation by exercise and Bovril were evaluated. About 25% of normal adults responded to exercise and Bovril stimulation whilst only 2% obese subjects responded to exercise and nonc to Bovril. In pubertal boys, the response rates to exercise and Bovril stimulation were 50 and 0% respectively. Although a number of the pubertal boys did not

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Ph.D. Thesis

respond, they already had raised FGH levels (> I7 mlU/L), indicating G H sufficiency. Hence, basal FGH measurement is important in the interpretation of dynamic test results.

There was no significant difference in FGH levels measured i n mild and moderately malnourished children compared to normal, Tanner-matched children. However , malnutrition was found to affect the insulin-like growth factor (IGF-I) levels in pre-pubertal children. IGF-I levels decreased significantly (p<0.01) with body mass index (BMI). FGH levels were found to be affected in other endocrine diseases with impaired glucose tolerance. Due to the wide variations in FGH

levels, this study confirms that an oral glucose tolerance test (OGTT) is required for diagnosis of GH excess in acromegalic patients. Median FGH levels of insulin-dependent diabetes (IDDM) in both young (18-44 years) and old (45-8 1 years) patients were significantly elevated when compared to age-matched controls (p<0.001). In the IDDM group, FGH levels were associated with glucose intolerance since there was a significant positive correlation with glycated haemoglobin (gHb). However, in non-insulin dependent diabetic patients (NDUM), FGH levels were normal. Thus, measurements of basal o r stimulatedl suppressed GH levels are of great importance in a variety of endocrine diseases.

r Seroepidemiological, immunological, and m.olecular studies of

Mycobacte~~iunz leprae infection.

(Abstract of thesis submitted by Gan Seng Chew to the University of Malaya in April 1991 for the degree of Doctor of Philosophy).

M . Leprae cell wall and cell wall associated constituents such a5 phwulic glycolipid (PGL) and lipoarabinomannan B (LAM B) are highly immunogenic, inducing strong humoral antibody responses and causing the suppression of cellular inununity.

Results f rom a three-year national seroepidemiological study involving about 40,000 individuals selected by stratified sampling showed that PGL immunoassays can

be used as a screening tool in leprosy control progr-armies. Scrupusilivily lo PGL ariligcns correlated with the prevalence rate in a defined population. The use of M. leprae specific antigens, such as PGL, in immunoassays could thus be used as an indicator of exposure to M. lepme.

Individuals with subclinical infection had higher antibody ti ters and could be differentiated from those who had been exposed

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PI1.D. Thesis

and became immune. High antibody titers, especially of the IgM class, were found in higher frequencies among individuals staying in high prevalence communities and in leprosy patients. IgG antibodies were found in significant quantities in individuals staying in low prevalence communities and in leprosy patients treated over a long period of time. A gelatin particle agglutination test (GPA) which de~eck, IgM-arili-NT-BSA was used as a field test in the seroepidemiological sti~dies i n Malaysia and was shown to have vely good concordance with the reference ELlSA test.

The lymphocyte responses of lepromatous (LL) patients to M. leprae, BCG and PPD antigens were significantly lower than those of tuberculoid (TT) patients, indicating that lymphocytes of LL patients recognize M. Iepme related antigens of BCG and PPD. The T cell

unresponsiveness in LL was M. leprae antigen specific. In vitro cultures of spleen cells from boosted mice with M. leprae antigens showed a decrease in CD45RA+CD8+T cell subsets, probably due to the development of cytotoxic effectors within the CD45RA-low CDS T cell subset.

A genomic library of M. leprae isolated directly from leprvsy patients' skin biopsies (in contrast to the available M. leprae genomic libraries which consist of DNA from M. leprae grown in armadillos experimentally) was constructed. Thirty-nine immunologically reactive clones were identified by pooled LL patients' serum. Three of the 39 immunologically reactive clones were also identified by pooled TT and BT patients' senim. Further work is being carried out to identify antigenic epitopes that would stimulate protective immunity.

I Production and characterization of monoclonal antibodies against the malarial parasites

Plasmodizmz fi&iparum and Plasmodium cynomolgi.

(Abstract of thesis submitted to the University of Malaya by Patricia Lim Kim Chooi in September 1991 for the degree of Doctor of Philosophy)

T h e objective of this study was to produce immune protection of the host. Monoclonal monoclonal antibodies against the mrtlaria antibodies were produced against P. falciparum parasites Plasmodium falcipururn and and P. cynomolgi schizont antigens using the Flasrnodiurn cy nurriulg i f u ~ u se iri hybl idvrlia technique. The imilluiioglobulin immunodiagnosis and for the identification of class/subclass of 9 of these monoclonal antigenic epitopes that may be involved in antibodies was determined. Of the 5

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Ph.D. Thesis

monoclonal antibodies produced against P. falciparum, 1 was of the IgG subclass while the other 4 were IgM. All the 4 monoclonal antibodies produced against P. cynomolgi were IgM.

These 9 monoclonal antibodies cross-reacted extensively with the trophozoite and schizont antigens of P. falciparum, P. cynomolgi, P. inui and Z'. berghei in the enzyme-linked immunosorbent assay (ELIS A). However, in the indirect fluorescent antibody test (IFAT), all tne 9 monoclonal antibodies reacted at different intensities only with the schizonts of P. falciparum, P. cynomolgi and P. inui. No reaction was seen with either the ring or trophozoite stages of these Plasmodium parasites.

In the counter-immunoelectrophoresis (CIE), 6 of these monoclonal antibodies (PF-IE4, PF- 1F6, PF-lG8, PF-1H5, PC-1E12, PC-1A11) precipitated one band each with both the trophozoite and schizont antigens of P. falciparum, P. cynomolgi and P. inui, while 2 of them (PF-1G8 and PC-1 A1 1) also precipitated a band with 2'. berghei trophozoite and sc lbml antigens. In~munoblot analysis showed that 4 monoclonal antibodies produced against P. falciparum schizont antigen; (PE-lE4, Ph- 1E12, PF-1F6, PF-lH5) recognised single antigenic epitopes in both the trophozoite and schizont extracts of P. falciparum. One monoclonal antibody produced against P. falciparum ((PF-1G8) and 3 against P. cynomolgi schizont antigens (PC-1A11, PC- 1E12, PC-1H12) recognised two or more epitopes present either in P. fnlcipantm or P. cynomolgi trophozoite and schizont antigens.

Immune sera from Orang Asli living in malaria

endemic areas in Peninsular Malaysia identified several polypeptide bands in P. falciparum and P. cynomolgi trophozoite and schizont antigens by immunoprecipitation and immunoblotting respectively. Four dominant polypeptides present in P. falciparum trophozoite and schizont antigens recognised by these sera were

of molecular weight 120, 90, 88 and 82 kilodaltons. In imrnunoblots with P. cynomolgi antigens, these sera reacted strongly with polypeptides of molecular weight 120, 105,96, 86 and 70 kilodaltons. These polypeptides should be further studied to determine their usefulness as diagnostic antigens.

he in vitro inhibition assay performed with two Malaysian isolates of P. falciparum (Gombak A and Gombak C), showed that the highest percentage inhibition was seen in cultures with ascites of PF-lG8 followed by PC- 1E12 and PF- 1E12. These monoclonal antibodies not only reduced parasite growth but also affected the development of trophozoites and schizonts as demonstrated by the presence of abnormal forms seen under light microscopy. The antigenic epitopes recognised by these inhibilor y rrivnuclorlal antibodies may bc involved in immune protection of the host against malaria infection.

Two of these monoclonal antibodies namely, PF-1G8 and PC- 1E12 were also able to detect circulating plasmodia1 antigens in the sera of patients infected with either P. falciparum, P. vivm or P. malariae in the sandwich-ELISA. The sensitivity of this ELISA with PF-1G8 and PC-1E12 was 96% and 98% respectively while the specificity of the te.st with both monoclonal antibodies was 100%. These two monoclonal antibodies are therefore potentially useful as seroepidemiological tools for malaria.

Page 39: IMR Bulletin Dec 1992

Training

Diploma in Medical ( Laboratory Technology

T h e Institute for Medical Research is the training ccntrt: i n rrledical laboratory technology in Malaysia. The year 1991 saw the replacement of the Certificate i n Medical Laboratory 'l'echnology course with the Diploma in Medical Laboratory course.

The diploma curriculum is a full-time 3-year course divided into 6 Semesters of 24 weeks each. It consists of basic science for six months followed by laboratory technology for 1 112 years, and by specialisation in the final year. The summary of the curriculum is as follows :

DIPLOMA COURSE IN MEDICAL LABORATORYTECHNOLOGY

3 (24 WEEKS)

POLYVALENT

YEAR 2 SEMESTER

YEAR I SEMESTEK

1 24 WEEKS

2

(24 WEEKS)

POLYVALENT

4

(21 WEEKS)

DISCIPLINE

DISCIPLINE

ACADEMIC SCIENCE 1. Biological Chemistry 2. Anatomy/Physiology 3. Laboratory Equipments/Physics 4. Statistics/hlathcmatics/nasic

Computing I 5. Genetics 6. Immunology 7. Introduction to I'athology

C\'TROIlUCITON TO MEDICAL

LAIIORATORY TIiCHNOI.0G.I'

1. Chemical I'athology

2. hledical Microbiology

3. Medical Par~sitology

4. 11acmatology

5. Blood Transfusion Services

6. Cy~ology

7. A~~il~urrr i~al Pa~oluyy

POLYVALENT

FIELD I (LOG BOOK) 1. Chemical Pathology 2. Medical Microbiology

3. Medical Parasitology 4. IIaematology 5. Blood Transfusion Services 6. Cytology 7. Anatomical Pathology

ADVANCED MEDICAL LABORATORY TECHNOLOGY

1. Chemical Pathology 2. Med~cal Microb~ology 3. Medical Parasitology 4. Haematology 5. Blood Transfusion 6. Cytology 7. Anatomical Pathology

I EVALUATION AKD COUNSELLlhTG

YEAR 3 SEMESTEK

5

(24 WEEKS)

HLVALEN I

6 (24 WEEKS) BIVALENT

- --

DISCIPLINE

FIELD I1 - ADVANCED ( LOG BOOK ) in one of the following bivalent modules :- Module 1 : Chemical Pathology and Kutrition Module 2 : Medical Microbiology and Mcdical Parasitology hfodule 3 : Haematology and Blcod Transfusion Module 4 : Anatomical Pathology and CyLology

1. One of the above modules 2. Basic Computing 11 3. Laboratory Management

EXAMISATION (DIPLOMA)

This new programme aims to produce high calibre medical laboratory technologists, who will be able to provide an efficient laboratory service of high quality. The annual student intake is expected to be 120 and the course commences in November each year.

Page 40: IMR Bulletin Dec 1992

A Function of IMR

The Division of Labratory

Rearing laboratory animal is an integral part of any medical research insitution. The animals are used as models in the study of disease pathogenesis, chemotherapy and diagnosis.

The Division of Laboratory Animal Rexoi~rcc~ or the Animal House (as it was known earlier) began with the establishment of the IMR. It was set up with three following main objectives: i. to produce laboratory animals for the research and diagnotics needs of the Institute, ii. to provide veterinary care and to advice researchers using laboratory animals, and iii. to undertake research.

Today ten species of laboratory animals are maintained in the Division. These include mice, rabbits, guinea-pig, monkeys, sheep, geese and mouse-deer. The latest addition is a colony of specially bred mutant mice (nude mice) which was established in 1991. These specific pathogen-free mice are maintained in the isolators to ensure survival. Approximately 25,000 to 30,000 laboratory animals are produced annually to meet the request of the reseachers in the IMR as well as in the departments in the Ministry of Health and occasionally the universities.

Management of these animals encompases 3 aspects, that is housing, nutrition and sanitation.

These animals are kept mainly in cages lined with autoclaved wood shavings and these are stacked i n racks in nat~irally ventilated moms. Diet consisting of locally produced pelleted formulas and water, is given ad. libitum daily to the animds. Vegetables are also givcn to thc guinea pigs and monkeys. Sanitation, which is vital in ensuring a disease minimum condition, is achieved rhrough regular cleaning and disinfecting.

Veterinary assistance, one of the main functions of the Division, is provided at the request of the researcher. Assistance includes treatment, post- mortem, blood taking and surgery as well as advice on management, animal diseases and anaesthesia. With the formation of an Animal Care and Use Committee in the IMR, all projects using animals as models in their studies require the approval of this Committee, whose function is to ensure the ethical use of animals.

As it is important to me high quality ariirnals in research, efforts are being made to upgrade the level of management of the laboratory animals. A survey done recently to determine the level of management in Malaysian laboratory animal facilities has shown a lack of quality control in animal production. Laboratory animal centres exchange animals and therefore efforts are being made to standardize management practices in all the centres.

Page 41: IMR Bulletin Dec 1992

Courses and Workshops

Courses and Workshops

ii Technical Training course on Gastrointestinal Infections

A SEAMIC Technical Training Course on Gastrointestinal Infections was held at the Institute for Medical Research, 27-31 January 1992. It was sponsored by Southeast Asian Medical Information Cen treIInternationa1 Medical Foundation of Japan(SEAMIC/IMFJ), in collaboration with the Ministry of Health Malaysia. The objectives of this training course was to upgrade knowledge and skill of the participants in the detection of enteric pathogens and to disseminate information on the recent advances i n gastrointestinal infections.

The lectures and laboratory practicals were conducted by Prof Dr Hideo Hayashi of Tsukuba University and Prof Dr Takeshi Honda of Research Institute for Microbial Diseases, Osaka University. Dr Narimah Awin of Ministry of Health Malaysia was invited as guest lecturer to give a talk on the epidemiology of enteric bacteria in Malaysia. Nine participants, four from local universities, three from hospitals and two from the IMR, attended the Course.

The Course covered aspects of bacterial virulence and methods to detect virulence factors, including the application of gene probe and Polymerase Change Reaction (PCR). Emphasis was on the virulence factors of Escherichia coli, Vibrio cholerue and F7iBrio pcrrahaemolyticus and available methods for detecting haemolysins and enterotoxins

produced by these bacteria. In addition to the conventional methods, participants were introduced and given oppurtunity to have hands-on experience with commercial test kits such as reversed passive latex agglutination and enzyme-linked-immunoassays (ELISA) for dctcction .of haemolysins and enterotoxins, and with gene probe in the colony hybridization of enterotoxigenic E. coli.

Attendance certificates were given away by Tan Sri Dato' Dr Abu Bakar Suleiman, Director General of Health Malaysia who is also the Chairman of SEAMIC Coordinating Committee for Malaysia.

Contributed by Cheong Yuet Meng

National Quality Assurance Workshop on Laboratory Services

T h e Quality Assurance Programme (QAP) Ministry of Health, Malaysia (MOH) cncompasscs a few disciplines, including laboratory services. The IMR is the Secretariate for the QAP in Laboratory Services. The main c u m m i l ~ t x for this programme was formed in September 1990 and its members consists of the officers managing laboratories, i.e pathologists, research officers, scientific officers and technologists as well as a few clinicians who represent laboratory users. Its first activity was the National Quality Assurance Workshop for Laboratory Services, 3-4 December 199 1. Ninety-three officers

Page 42: IMR Bulletin Dec 1992

Courses and Workshops

attended this Workshop. The main objective was to introduce and discuss the concept of QAP of the Ministry of Health and its implication on laboratory activities. Several papers were presented. Four subcommittees were formed, namely for chemical pathology, medical mic~~obiolog y , haematulug y arid blvod banking, and histopathology 'and cytology. These subcommittees discussed indicators, such as analytical performance and turnaround time for their individual disciplines. Six indicators were thus identified for the testing of the pilot project in early 1992.

Contributed by 7 ~ k i u h 1smuil

Fifth Asian Course in Tropical Epidemiology

T h e Fifth Asian Course In Tropical Epidemiology was organised by the Division of Epidemiology and Biostatistics, IMR and was

held at the Asia Hotel, Kuala Lumpnr from 28 October to 15 November 1991.

It was fundcd by the Regional SEAMEO TROPMED and Public Health Project, the German Agency for Technical Cooperation (GTZ) and the Australian Expert Technical Assistance Fund. There were 42 participants from Thailand, the Philippines, Indonesia and Malaysia. They included medical doctors, dentists, veterinarians and scientists.

The lecturers were from Australia, Canada, Indonesia, Philippines, Thailand and Malaysia. The course included lectures on epidemiology and biostatistics, paper critiques, practical exercises and a field trip to a health centre and district hospital in Selangor. The participants were given hands-on experience in the application of computer programs in epidemiology. They were alsv made LO

deliberate on a variety of problems and study designs, and formulate research proposals.

Contributed by Lye Munn Sann

National Quality Assurance Workshop

Page 43: IMR Bulletin Dec 1992

Pengerusi : Dato' M, Jegathesan Penyunting : Josephine L. Ireland Penterjemah : Rahimah Ahmad

Mohd. Zainuldin b. Talib Penolong : Mohd. Fo'ad b. Kastaman~

Norashiken bt. Lajis

Page 44: IMR Bulletin Dec 1992

Bangunan IMR - 1977

Bangunan IMR - 1901

Institut Penyelidikan Perubatan

(Institute for Medical Research) Jalan Pahang

50588 Kuala Lumpur Malaysia

Tel: 03-2986033

Fax: 03-2920675