100 Years of Research in Sarawak

100 years of Biomedical research in Sarawak

Datu Dr Andrew Kiyu (Consultant Epidemiologist, Sarawak Health Department) Partly based on work done with Dr Goh Pik Pin [1] and Dr Kirubashni a/p Mohan [2]

Presented at Sarawak Development Institute, Kuching. 6 October 2016

[1. Director, National Clinical Research Centre, Ministry of Health, Malaysia] [2. Medical Officer, Clinical Epidemiology Unit, National Clinical Research Centre, Ministry of Health, Malaysia] 1 Objective of presentation

• To show a mosaic of the • topics of biomedical research carried out in Sarawak over the past 150 years,

• To give us a glimpse of the • determinants of health, • health and disease conditions, and • health status, and • how they have changed over the past 150 years or so.

2 CRC

Plants, 2015

- Esoterica; Cardiovascular diseases; Cancers; Parasitic infections; Bacterial infections; Viral infections Environmental health; Nutrition health; Time span: 1915Timespan: Indigenous health; Health care delivery system; Topics scope: wide; 12 themes and subthemes Depth: shallow

3 4 Borneo Biomedical Bibliography 1996-2009

• Originally published by A. Baer and G.N. Appell in the Borneo Research Bulletin 27:77-89, 1996. • had 173 references. • 2nd Edition (2000) bibliography for the Institute of East Asian Studies, UNIMAS, Sarawak. • contains more than 330 references. • 3rd Edition (2009) Borneo Biomedical Bibliography • Contains 1079 references

Source: A. Baer. Borneo Biomedical Bibliography, 3rd ed. 2009.

6 Borneo Biomedical Bibliography Introduction to 2nd ed. 2000

• The selected reports provide an overview of the health status of ethnic Bornean groups. • Yet a coherent picture is elusive, • since the studies were done at different times and places with disparate aims. • no single report provides a thorough health survey of any particular group, • one in which all ages were surveyed.

Source: A. Baer. Borneo Biomedical Bibliography, 3rd ed. 2009.

7 Borneo Biomedical Bibliography Introduction to 2nd ed. 2000 Moreover, even for so dire a disease as malaria, • little longitudinal information is available, • despite the fact that 70% of reported malarial cases in Malaysia in 1990 were from Sabah (Lim, 1992). • an early malarial survey of Sarawak and Brunei (de Zulueta, 1956) provides reliable information only • on age 2-9 yrs. • at single time points in various areas, • despite known seasonal and annual variation in malarial parasitemia.

• Recent malarial reports have not built systematically on this 1956 survey base. 8 Source: A. Baer. Borneo Biomedical Bibliography, 3rd ed. 2009. Borneo Biomedical Bibliography Introduction to 2nd ed. 2000

Some longstanding health problems in Borneo include • Malnutrition - childhood and adult, • filariasis, • intestinal parasites, • malaria, and • some microbial infections.

Source: A. Baer. Borneo Biomedical Bibliography, 3rd ed. 200.

9 Borneo Biomedical Bibliography 2000: Some longstanding health problems in Borneo

Tetanus neonatorum (tremendous improvement) • Schwenk (1975) reported that the Iban once had “one of the highest” incidences in the world of tetanus neonatorum, or newborn lockjaw; • this resulted from cutting the umbilical cord with an unsterlised bamboo splinters (slivers), and • controlling bleeding of the cord with kitchen-fire ashes, • but the administration of anti-tetanus toxoid (ATT) now to antenatal mothers • has reduced this form of tetanus to a very low level, at least in Sarawak (A. Kiyu, Personal communication) Sources: • Schwenk R. Village and regional determinants of family innovativeness among the rural Iban of Sarawak Malaysia. Ph.D dissertation, Cornell Univ., Ithaca, New York 1975. (On the Rejang River area). • A. Baer. Borneo Biomedical Bibliography, 3rd ed. 2009. 10 Example of kitchen-fire ashes that were applied to umbilical cords of newborns

Sina Rang Lemulun Homestay, Bario Asal, Kelabit Highlands, Sarawak https://media-cdn.tripadvisor.com/media/photo-s/08/85/76/c7/sinah-rang-lemulun-homestay.jpg

11 Borneo Biomedical Bibliography: Introduction to 2nd ed. 2000

Conditions on which little has been published include • complications associated with pregnancy or childbirth (that is, female reproductive health), • geriatrics, • childhood communicable diseases, • dental problems, • venereal diseases and • genetic disorders, to name a few.

• With notable exceptions, health-oriented demography has also been neglected …

• Source: A. Baer. Borneo Biomedical Bibliography, 3rd ed. 2009.

12 Borneo Biomedical Bibliography: Introduction to 2nd ed. 2000 • Borneo ethnic groups received vastly different amounts of attention in biological or biomedical journals • Kayan/Kenyah – only biomedical reports on them are on nutrition and malaria • Ibans – have at least 8 biomedical topics

• Source: A. Baer. Borneo Biomedical Bibliography, 3rd ed. 2009.

13 Borneo Biomedical Bibliography: Introduction to 3nd ed. 2009

• “Much of human life has changed radically over the past few centuries in Borneo and elsewhere … • Those changes have been lost to human memory or is now vanishing during our lifetimes • Fuller information on people, their environments and cultures, and all other basic elements of existence and experience • can only help enrich our understanding of human life, now and into the future • The goal of biomedical research is to foresee (the) myriad of problems and inform our fellow human beings as to possible ways to solve them”

• Source: A. Baer. Borneo Biomedical Bibliography, 3rd ed. 2009. 14 Major studies on Iban, Bidayuh, Melanau, Malays, etc during the British colonial period

15 Socioanthropology and ethnographic research excluded in this presentation

• Report on a Melanau Sago Producing Community in Sarawak. Harold Stephen Morris. Issue 9 of Colonial research studies, H.M. Stationery Office, 1953 • The Land Dayaks of Sarawak. William W Geddes. London: Her Majesty’s Stationery Office, 1954 • Nine Dayak Nights. William W Geddes. New York: Oxford University Press, 1957 (144 pp.) • Report on the Iban. Derek JD Freeman. Athlone Press, LSE Monographs on Anthropology 41, 1955 (317 pp.) • World Within: a Borneo story. Tom Harrisson. London Cresset Press, 1959 • The Malays of South-West Sarawak before Malaysia: a socio-ecological survey. Tom Harrisson. London: Macmillan, 1970

16 100 years of biomedical research in Sarawak – a compilation

17 The publications (in the compilation) were grouped into eleven themes namely:

1. Health care system delivery, 2. Indigenous health, 3. Nutrition and iodine deficiency disorders, 4. Environmental health, 5. Virus infections (with 5 sub-themes) 6. Bacteria infections (with 4 sub-themes) 7. Parasitic infections (with 2 sub-themes), 8. Cancer, 9. Cardiovascular research, 10. Esoterica 11. Plants

Note: only those with Abstracts were included in the compilation. 18 Number of publications (in the compilation) by 10-year-intervals

Sarawak Independence CRC 2004 70 Japanese Occupation 22.7 – 16.9.1963 1941-1945 UNIMAS 1995 University Malaya Medical Faculty 1964 60 British Colony 1946-22.7.1963 Federation of Malaysia 16.9.1963 50 Brooke Rajah 1841-1946 40 30 20 10 0

HC IH NH EH VS BI PI MI CA CV ES PL

HC = Health care delivery system; IH = Indigenous health; NH = Nutrition health; EH = Environmental health; VS = viruses; BI = Bacterial19 infections; PI = parasitic infections; MI = Malaria infections; CA = Cancers; CV = Cardiovascular diseases; ES = Esoterica; PL = Plants Number of publications (in the compilation) by major research topics 30 25 20 15 10 5 0 HC IH NH EH VS BI PI MI CA CV ES PL 1915-1925 1926-1935 1936-1945 1946-1955 1956-1965 1966-1975 1976-1985 1986-1995 1996-2005 2006-1915

HC = Health care delivery system; IH = Indigenous health; NH = Nutrition health; EH = Environmental health; VS = viruses; BI = Bacterial infections; PI = parasitic infections; MI = Malaria infections; CA = Cancers; CV = Cardiovascular diseases; ES = Esoterica; PL = Plants 20 100 years ago somewhere along Sarawak River

21 Kuching and Sarawak River as it might have been in 1915

22 Source: http://ssoonz.com/history/ Borneo Company Limited, formed in 1856, is one of the oldest companies based in Sarawak and Sabah.

23 Borneo Company Limited

• founded on 8 May 1856 in London • to exploit the business opportunities in Sarawak

• The Borneo Company offices in Kuching were on the spot near the Tua Pek Kong temple now occupied by the Hilton hotel.

• The manager's house, 'Aneberg', The Kuching Borneo Company building in 1896. https://en.wikipedia.org/wiki/Borneo_Company_Limited#/media/Fil was on the hill above. e:Kuching,_Sarawak;_the_Borneo_Company%27s_building._Photogr aph._Wellcome_V0037398.jpg

The company merged with the Inchcape Group in 1967

https://en.wikipedia.org/wiki/Borneo_Company_Limited http://eresources.nlb.gov.sg/infopedia/articles/SIP_1248_2007-07-02.html 24 Excerpts from Christie’s paper

• I wished to find the main reservoir of intestinal parasitism; • I set to work to test 100 Malays living on the banks of the Sarawak River in their usual fashion, in palm leaf houses on high piles on the edge of the river. • Most people are probably now aware that Malays let all their sewage run into their river. • They squat for defaecation in it, and drink from near the same spot, trusting to the current and tide for cleansing. • They love their river, are always bathing, swimming, boating, drinking, or fishing in it. • To the casual observer they appear as a happy, clean family sporting beneath their cocoanut palms and fruit trees. … Source: W. Ledingham Christie. Further investigation into latent dysentery and intestinal parasitism in Sarawak, Borneo. British Medical Journal. (17 July) 2:89-90, 1915. 25 Excerpts from Christie’s paper

One of our Malays manages to struggle through his work as boatman and carpenter with • filaria in his blood, • amoebae, • ankylostoma, • round-worms and • whipworm in his alimentary canal, having • already become immune to malaria, which is found more frequently in the young.

• With no small effort, and by • sending this man and a laboratory assistant up and down the river, • we managed to get good specimens of faeces in Petri dishes, carefully labelled, • from 100 Malays—men, women, and children—in the order in which they offered, without any reference to present or past illnesses. • The women were somewhat shy, and are therefore in the minority. 26 Source: W. Ledingham Christie. Further investigation into latent dysentery and intestinal parasitism in Sarawak, Borneo. British Medical Journal. (17 July) 2:89-90, 1915. Results

Organism % of samples Amoeba histolytica: 59 Ankylostoma duodenale (or americanum): 59 Monads (Trichomonas, 63%, Cercomonas, 3%): 66 Round-worm (Ascaris lumbricoides): 79 Whipworm (Trichuris trichiura): 84 • Each person had several sorts at once—in fact, in 17 per cent, five were observed on the same slide, namely, ankylostoma, amoeba, monads, roundworm and whipworm. • The figures are well under the mark, for in twenty cases which were previously negative, where we got a second specimen, we found amoeba in 50 per cent.

Source: W. Ledingham Christie. Further investigation into latent dysentery and intestinal parasitism in Sarawak, Borneo. British Medical Journal. (17 July) 2:89-90, 1915.

27 Results • Those Malays who came to Sejijak Hospital afterwards for medicine, • did not complain of any symptoms, • but some looked pale and thin, • while others, who appeared normal, were not up to a fighting or athletic standard of vigour. • On inquiry among 83 whom we were able to meet • Among those positive for amoeba: • 34 could remember having had dysentery, • 26 could not • Among those negative for amoeba • 10 had had dysentery, and • 13 had not.

• Source: W. Ledingham Christie. Further investigation into latent dysentery and intestinal parasitism in Sarawak, Borneo. British Medical Journal. (17 July) 2:89-90, 1915. 28 Life cycle of Amoeba Histolitica

• vast majority of cases is asymptomatic • the carrier is unaware they are infected. • ≈ 10% causes disease. • Infections can last for years • asymptomatic, • vague gastrointestinal distress, • dysentery (with blood and mucus). • Most infections occur in the digestive tract • other tissues may be invaded. • Complications include • ulcerative and abscess pain and, rarely, 30 • intestinal blockage. http://media.eol.org/content/2011/10/06/00/42788_orig.jpg Transmission of amoebiasis

Amebiasis is transmitted by • fecal contamination of drinking water and foods, but also by • direct contact with dirty hands or objects, as well as by • sexual contact.

32 HEALTH CARE DELIVERY SYSTEM

34 Selected Publications in Health Care System Delivery

• A Primary Health Care Project in Sarawak • Paul Chen Chieh Yee, Y.K. Tan. Med. J. Malaysia Vol. 37 No. 1 March 1982 • Thirty Years of Village Health Promoter Programme in Sarawak: Promoting Health in the Community • Abdulhan Bin Mohamed. International Journal of Public Health Research Special Issue 2011 (Symposium), page 21

• A study of patients admitted to Miri Hospital, Sarawak, by airborne medical evacuation. • Kiyu A. Med J Malaysia Vol 41, No. 2, June 1986.

35 Health Care Delivery System:

Village Health Promoter Programme

36 35 years of Village Health Promoter Programme

1981 the Village Health Promoter Project was formulated and Tested as a pilot project in Tebakang in 1981 1983 Inaugurated as the VHP Programme 1985-1986 a major assessment and review of the programme was undertaken by the Institute for Medical Research and from which the 1987 VHP manual was produced. 1999/2000 The second evaluation conducted to assess the long-term impact of the programme on the health status of the communities involved 37 Village Health Promoters (VHPs)

These VHP from Bario have completed their training and are ready to go home to serve their communities

38 A VHP attending to a patient

39 Health Care Delivery System: Flying Doctor Service and MedEvac

40 FLYING DOCTOR SERVICE

An FDS clinic at a remote location. FDS doing a medical evacuation of the seriously ill and other emergency cases.

FDS – introduced as a pilot project in Sept. 1973; permanent service in May 1975 Source: Sarawak Medical and Health Department Annual Report 1975 41 MEDEVAC

https://sarawakonline.wordpress.com/2012/06/21/sarawak-civil-service-set-bar-for-excellent-service/ • Top five causes for MEDEVAC in 1986: • Bronchopneumonia • Accidental falls • Gastroenteritis • Peptic ulcers • Appendicitis • 7.8% of MEDEVAC patients died in hospital • 63.6% of MEDEVAC were considered justified (based on pre-set criteria)

Source: Kiyu A (1986). A study of patients admitted to Miri Hospital, Sarawak, by airborne medical evacuation. 42 Med J Malaysia Vol 41, No. 2, June 1986. INDIGENOUS HEALTH

43 • Kiyu, A. The availability of some household items among Penan households in the Lio Mato area, Upper Baram, Sarawak. Sarawak Gazette 113:15- 24, 1986.

44 The availability of some household items among Penan households in the Lio Mato area

http://penantongtana.blogspot.my/2010/08/asik-nyalit-family-of-ba-ubung.html45 Semi-nomadic Penan with their utensils. 46 Paul CY Chen (2016). The Penan: Forest nomads of Sarawak in transition. p60 Availability of 159 household items among Penans in Lio Mato area 1986

Purpose of item Items % of households having at least one item

Hunting blowpipe 89.3

shotgun 31.7

Blowpipe or shotgun or 95.0 both Farming, gardening and Parang, axe, chainsaw Parang 95.0 cutting Axe 90.0 parang bengkok, hoe, spade 15.0 Carrying, boiling and Pail, kettle and water Pail: 58.5; Kettle: 62.1; storing boiled water container Water container: 31.4 Cooking Pot, kuali, ladle Cooking pot: 1.6 per household; Kuali: 70.4; ladle: 76.6 Drinking and eating Plate, cup, spoon Plate: 83; cups: 46.5; Spoon: 67.3

Lighting Damar, pelita, kerosene Damar: 61; pelita: 15.1 lamp, lighter Disease prevention Mosquito net, toothbrush Mosquito Nets 32.7; 0.1 toothbrush per person Telling time and getting Watch and radio Watch: 35;2; Radio: 11.3 outside news 47 NUTRITION AND IODINE DEFICIENCY DISORDERS (IDD)

48 NUTRITION AND IODINE DEFICIENCY DISORDERS (IDD) Nutrition studies by Dr AJU Anderson 1970s

49 Reports on nutrition research among Ibans by Dr AJU Anderson

• Food consumption of the Lemanak River Iban • Nutrition of Iban children of the Lemanak River • Nutrition of Iban children of the middle Mukah River • Nutrition of Iban children of the Sut and Mujong Rivers (Kapit) • Nutrition of Iban primary school children of Lubok Antu District

50 Reports on nutrition research among Kayan/Kenyah, Malay, Melanau and Penan by Dr AJU Anderson

• Nutrition of Kayan and Kenyah Children of the Middle River Baram River. Sarawak Gazette (30 Nov):241-248, 1978 • Nutrition of Malay Children of the Sarawak River Delta • Nutrition Of Melanau Children Of The Tillian River • Subsistence of the Penan in the Mulu Area of Sarawak • By A.J.U. Anderson, M.D. (Lond.) D.T.M. &H (Eng.) • Clinical Specialist (Nutrition), Sarawak Medical Service • Published in The Sarawak Gazette (30 Nov.):204-216, 1979

51 Reports on nutrition research among Land Dayaks by Dr AJU Anderson

• Food consumption of Land Dayaks in the Tebakang area • Outline nutrition of Land Dayak Children – Final Report • Summary nutrition of Land Dayak Children

52 General/summary reports on nutrition research by Dr AJU Anderson

• Notes on Food supply in Sarawak hill areas • Malnutrition among Sarawak children and remedies • Malnutrition among Sarawak children from four communities

53 Photographs taken during Applied Nutrition Programme (ANP) Nutrition Survey Source: Sarawak Medical and Health Department Annual Report 1975

Applied Nutrition Programme (ANP) Nutrition survey at Tebakang, 1975. 54 Dr A.J.U. Anderson taking measurements for statistical compilations. Rural life in Sarawak is centred around a village or longhouse. A longhouse is a village and may contain from 20 to 100 individual doors or families. Photo illustrated above shows the exterior of a typical longhouse. 55 Applied Nutrition Programme (ANP) Applied Nutrition Programme (ANP) Nutrition survey at Tebakang, 1975. Nutrition survey, 1975. Requesting stool specimen for Collecting sample of drinking water for examination with respect to 56 chemical analysis at Payau Berus. helminth ova. Applied Nutrition Programme Applied Nutrition Programme (ANP) Nutrition (ANP) Nutrition survey, 1975 survey, 1975 showing school children being lined showing thin and growth- up for physical examination at Engkaroh retarded children at Engkaroh 57 Importance of Padi and Rice in Iban culture

• The great majority are padi farmers, • rice being by far the most important food • having a leading place in the Iban religion, • followed by nearly all, but a small number of Christians. • The tradition is that the gods themselves first taught the Iban how to cultivate padi, • and all the proper observances to avoid offending the spirits and secure a good crop. • These aspects are described by Eric Jensen in • ‘The Iban and Their Religion’ (Clarendon, Oxford, 1974), • much of whose studies were of the Lemanak people. • AJU Anderson. Food Consumption of the Lemanak River Iban. Sarawak Health Department mimeograph document. 1977

58 Environment and Income

• Hills are usually quite steep, • serious erosion occurs with extensive loss of forest cover, • secondary jungle or coarse lallang grass (Imperata cylindrica). • Padi is replanted before the soil can recover, resulting in very poor crops: • the 1976 harvest lasted only 3.5 months on average for 431 families • at five longhouses there was complete crop failure. • Large proportions of money evidently have to be spent on buying rice or other foods. • There is some income from rubber and pepper, • otherwise men seek employment elsewhere, • leaving women and older men to carry on most of the farm work. Source: AJU Anderson. Food Consumption of the Lemanak River Iban. Sarawak Health Department mimeograph document. 1977 59 Food Habits

• Rice is preeminent as a food, • is eaten three times a day whenever possible. • Other foods are subsidiary, or set as a relish, • or else as a poor substitute like tapioca and sago. • Fish are caught by nets, lines and traps, with home-made spear-guns (the Iban – and others – are most ingenious in constructing such devices with limited materials), and • sometimes illegal tuba or poison. • Fish and other aquatic foods figure prominently in diets, and • less often meat, usually from hunted or trapped animals or sometimes birds. • Domestic pigs and chickens are occasionally eaten, • normally after being sacrificed for ceremonial or ritual purposes. • For religious or customary reasons various foods may be banned to certain families, e.g. python meat is tabu to many. • Source: AJU Anderson. Food Consumption of the Lemanak River Iban. Sarawak Health Department 60 mimeograph document. 1977 Vegetables

• Vegetables are restricted and often seasonal, • being planted with or among padi. • Tapioca leaves are important. • Other semi-wild or wild items such as • ensabi (‘Iban mustard’) or • fern (paku) and Ensabi • shoots, e.g. wild sago palm (pantu) or bamboo are often consumed. • Fruit is similarly represented by a number of cultivated, semi-wild and wild varieties. • The Iban frequently prefer to forage for wild sources rather than grow their own crops. • Source: AJU Anderson. Food Consumption of the Lemanak River Iban. Sarawak Health Department mimeograph document. 1977 61 Nutrient Intakes Below 80% Adequacy (% Persons)

Protein Calories Calcium Iron A Bı Ribo. Nia. C 1-2 yrs. 53 90 88 100 37 90 90 94 33 Other 6 22 90 65 41 39 90 24 12 age groups

Source: AJU Anderson. Food Consumption of the Lemanak River Iban. Sarawak Health Department mimeograph document. 1977

62 Protein-calorie Malnutrition and Stunting among 4106 Sarawak Children under 9 Years Old by WHO Standard Weights and Heights

Wasting: Stunting: Weight for Age (%) Heights for Age (%) Origin Number Severe Moderate ‘Severe’ Moderate + 60% or + Severe below 85% Severe Less 80% or below 90% Less Tiliian Melanau 485 6.6 74.2 9.8 42.9 Ulu Mukah Iban 562 11.0 82.5 16.7 54.2 Lemanak Iban 505 13.5 89.7 29.1 72.5 Sut & Mujong Iban 502 9.6 86.1 18.3 63.1 Tebakang Land Dayak 696 8.3 85.2 12.5 52.7 Sarawak Delta Malay 516 8.7 83.9 9.3 48.4 Baram Kayan&Kenyah 710 3.1 66.5 13.1 49.7 Mulu Area Penan 130 7.7 92.3 20.1 60.4

Mean 4106 8.4 81.0 15.5 54.7

Source: AJU Anderson. Food Consumption of the Lemanak River Iban. Sarawak Health Department mimeograph document. 1977 63 Child Malnutrition in Developing Areas By Gomez Weight Categories

Severe Moderate Mod. + 60% or 61-75% St. Severe 75% less Wt. or less Latin America 1.6 18.9 20.5 Africa 4.4 26.5 30.9 Asia 3.2 31.2 34.4 Total ( 173, 000) 2.4 22.8 25.2 Sarawak (4, 106) 8.4 55.1 63.5

Source: AJU Anderson. Food Consumption of the Lemanak River Iban. Sarawak Health Department mimeograph document. 1977

Nutritional status of children in Sarawak in 2015 Obese: 1.02% Normal: 91.75% Moderate malnutrition: 5.96% Severe malnutrition: 1.27% Source: Nutrition Programme, Sarawak Health Department 64 Weights and Heights of Iban and Other Adults 20-49 Years Old

Origins Males Females

n Wt (kg) Ht (cm) n Wt (kg) Ht (cm) Lemanak Iban 47 50.6 158.3 57 43.5 147.9 Batang Ai Iban 129 49.1 - 164 43.1 - Tebakang Land Dayak 54 49.2 159.5 56 42.3 147.5 Penan (Eastern) 44 51.2 156.7 49 40.6 144.6 Punan Busang 25 53.0 156.7 22 38.0 146.8 Malay soldiers/ 1268 57.9 165.5 606 48.2 149.0 wives North American - 59.3 (158) - 49.2 (148)

65 Fate of 4626 Live-Born Infants from 943 maternal Histories (C. 1977) Esti- Chil- Infants Toddler -mated -dren Average Total Deaths Deaths Average Born Live Deaths Per per Mothers Age Alive Births (%) 1000 1000

Melanau 106 31.3 615 5.87 11.1 79.8 30.0 Mukah Iban 118 29.5 612 5.1 27.9 204.2 80.1 Lemanak Iban 116 30.4 445 3.8 18.4 141.6 22.5 Sut & Mujong Iban 107 33.6 588 5.5 14.1 156.2 42.5 Land Dayak 204 28.9 906 4.4 8.4 55.2 23.4 Malay 93 32.7 498 5.4 14.9 110.4 36.1 Kayan & Kenyah 147 34.0 713 4.8 23.4 158.5 80.0 Penan 52 39.0 249 4.8 29.7 180.7 73.0

Total 943 31.7 4626 4.9 17.2 135.8 48.5 Maternal Mortality Ratio (MMR) and Toddler Mortality Rate (TMR) in Sarawak, 2014 MMR=16.2 per 100,00 Live births (7 maternal deaths) TMR = 9.3 per 1,000 Live births 66 Source: MCH programme, Sarawak Health Department Recommendations

• Family Planning • Better agriculture • Use jungle leaf litter as fertiliser, • Plant Job’s tears

• Supplementary food Job’s Tears https://upload.wikimedia.org/wikipedia/ • Eat midin commons/d/de/Coix_lacryma-jobi1.jpg • Salt iodisation • Child feeding • Worm treatment • School meals • Weight and height monitoring • Stenochlaena palustris State Food and Nutrition Policy Midin 67 Rumah Jandok, Ulu Yong, Kapit. 2016-09-05

68 Shifting Cultivation for Hill Padi still being practised today, (Kapit 2016-09-05)

69 NUTRITION AND IODINE DEFICIENCY DISORDERS (IDD) Iodine Deficiency Disorders

70 Selected Publications on Iodine Deficiency Disorders in Sarawak in early 1970s

• Polunin I. Endemic goitre in Malaysia. Assignment Report. Regional Office for the Western Pacific. WHO 1971. • Ogihara T et al. Serum thyrotropic levels of natives in Sarawak. J Clinical Endocrinology Metabolism 35 (5):711-715, 1972 • Ogihara T et al. Endemic goitre in Sarawak, Borneo Island: prevalence and pathogenesis. Endocrinology Japan 19 (3):285- 293, 1972 (on upper Rejang Iban; iodine content of drinking water was very low) • Maberly GF and C Eastman. Endemic goitre in Sarawak. SEAJTMPH 7(3):434-442, 1976 (On Iban in Ai Region; 99% with goitre; cretinism 4% found only at Ai) 71 Selected Publications on Iodine Deficiency Disorders in Sarawak from 1990s

• Survey of Availability of Iodine-Enriched Salt in Sarawak. • A M Taha, T Zainab, D Lau, P Yeo. Med J Malaysia. 1995 Dec; 50(4):391-5 • Iodization of Village Water Supply in the Control of Endemic Iodine Deficiency in Rural Sarawak, Malaysia. • Foo LC, Zainab T, Goh SY, Letchuman GR, Nafikudin M, Doraisingam P, Khalid B. Biomed Environ Sci. 1996 Sep; 9 (2-3):236-41 • Iodine Deficiency Disorders in Sarawak, Malaysia • Kiyu A, Tambi Z, Ahmad Y. Asia Pac J Clin Nutr. 1998 Dec; 7(3/4):256-61 • Socioeconomic Correlates of Iodine Status among School Children in Sarawak, Malaysia • Wah-Yun Low, Siti Norazah Zulkifli and Rajeswari Karuppiah. Asia Pac J Public Health 2002; 14(2): 110- 117. • Incidence of Thyroid Malignancy among Goitrous Thyroid Lesions from the Sarawak General Hospital 2000-2004 • Howe, T T; Hamdi, M M; Swethadri, G K; Wong, J O L; Soe, M M; Abdullah, M S. Singapore Med J. 2009 Jul; 50(7):724-8. • Iodine Deficiency Disorder and Goitre among School Children in Sarawak -A Nationwide Study • Lim Kuang Kuay, Chan Ying Ying, Ahmad Ali Zainuddin, Teh Chien Huey, Hasimah Ismail, Lim Kuang Hock and Kee Chee Cheong. International Journal of Public Health Research Vol 4 No 1 2014, pp (419-424)

72 Iodine Deficiency Disorders

Grades of goitre Grade Description 0 No goitre 1A Thyroid lobe larger than end of thumb 1B Thyroid lobe enlarged; visible with head tilted back 2 Thyroid enlarged with neck in normal position 3 Thyroid greatly enlarged; visible from about 10 m Elderly woman with a huge, longstanding multinodular goiter http://www.thyroidmanager.org/chapter/the-iodine- deficiency-disorders/ 73 Goitre surveys and prevalence in Sarawak 1970s to 1980s

74 Kiyu A et al (1998) Iodine deficiency in Sarawak, Malaysia. Asia Pacific J of Clin Nutr 7(3/4):256-261 IQ scores in three populations in Papua-New Guinea differing in iodine status

25 7.5% of newborns in Sarawak in 1993 had congenital hypothyroidism. 20 (Kiyu et al, 1995)

10 FREQUENCY (%) FREQUENCY

0 20-29 -39 -49 -59 -69 -79 -89 -99 -109 -119 -129 -139 -149 INTELLIGENCE QUOTIENT (IQ)

IODINE DEFICIENT (PRE-PROPHYLAXIS) IODINE SUFFICIENT – RURAL CONTROL IODINE SUFFICIENT – CITY CONTROL Boyages SC (1994). The damaged brain of iodine deficiency: evidence for a continuum of effect on the population at risk.

75 Interventions to Provide Iodine to the Population in Sarawak

• Salt iodisation plant in Kuching and Sibu (from 1957) • Provide iodised salt to antenatal mothers during antenatal clinic visits • Iodise salt for salt merchants (voluntary) to sell to the public (from 1979) • Legislation for sale of iodised salt in gazetted endemic goitre areas (Sarawak Public Health Ordinance 1983 • Iodination of gravity feed water supply system (1990s) • Universal salt iodisation (National Food Regulations 1985; Regulation 285 regarding Universal salt iodisation was added in 1990) • Took a number of years to take effect

76 Salt iodination plant, Sibu Central Pharmaceutical Laboratory and Store (CPLS); around 1970s

78 Wholesalers transporting iodised salt out of the Sibu Salt Iodisation Plant for distribution to various destinations 80 “Rhodiffuse” Iodinator For Piped Gravity-feed Water Supply

Villagers helping to install the idodinator into the village water The iodinator being attached to supply system (1990s). “Rhodifuse" system of Rh93ne-Poulenc- the village water system (1990s) Rorer-Doma (Antony, France)

81 ENVIRONMENTAL HEALTH

82 ENVIRONMENTAL HEALTH Rural Water Supply and Sanitation

83 Estimated Impact of Determinants of Health on Health Status of the Population

Source: Canadian Institute for Advanced Research, Health Canada, Population and Public Health Branch AB/NWT 2002. In, Philip O’Hara, “Creating Social and Health Equity: Adopting an Alberta Social Determinants of Health Framework”, 2005. Available at http://www.who.int/social_determinants/resources/paper_ca.pdf

84 Safe Water and Sanitation

The river was the main source of water for cooking, washing and bathing for the rural communities (circa 1960s)

85 Piped gravity-feed water supply in village

Pipeline criss-crossing the entire length from source to the kampung

A simple reservoir and intake point

Waterfall provides a good Former Chief Health source for a gravity feed Superintendent Sarawak, Mr. water supply system Jerome Runggol, instructing students on how to connect PVC The ‘convenience’ pipe pipes for gravity feed water gravity feed water supply supply. system provides the 86 householder Environmental sanitation

Domestic animals like these pigs were allowed to roam freely and scavenge under longhouses (early 1960s) 88 Sanitary latrines

Health Inspector, Richard Ibuh (2nd right) and a Rural Health Supervisor (extreme right) during a visit to Rh. Aji, Bakong to explain need for sanitary latrines 89 ⅓ of were fully functioning ⅓ of were partially functioning ⅓ of were not functioning

90 56% households had pourflush latrines • 91.3%, of latrines showed signs of recent use. • 90% of the women always used the latrine for defecation. • 86.5%, of the husbands always used the latrine for defecation • 47.6%) of the children below five years always used the latrine for defecation.

Most common reason for not using the latrine among adults • lack of water to flush the latrines • not being home when the need arises.

The reason for using the latrines were to • keep the compound clean, • convenience and • health reasons.

91 ENVIRONMENTAL HEALTH Healthy Settings

92 93 Healthy City Kuching (Launched in 1994)

The Right Honourable Chief Minister of Sarawak (2nd from right) launching the Healthy City Kuching Initiative in February 1995. With him are (left to right): Datu Awang Ehsan Joini, Mayor of Kuching North; Datuk Song Swee Guan, Mayor of Kuching South; and, Datuk Dr Stalin Hardin, Sarawak State Health Director.

94 Healthy Village Programme

Villagers of Rumah Jeffery Nundong worked with clinic staff to transform their longhouse under the Healthy Longhouse Initiative in Kapit 95 ENVIRONMENTAL HEALTH Effects of Transboundary Haze on Hospitalisation

96 1997 Transboundary Haze (API >800)

http://www.angelfire.com/myband2/adofcool/memorable/hazy/kchwaterf http://duwal.com/en/travel_gallery/Kuching%20waterfront%20- ront_me02_big.jpg %20Kuching.JPG

97 • The time-series analyses • statistically significant fire-related increases were observed in respiratory hospitalizations, • specifically those for chronic obstructive pulmonary disease (COPD) and asthma.

98 Findings of the study

• persons over age 65 years with • previous hospital admissions for any cause • any cardiorespiratory disease • any respiratory disease or • COPD • were significantly more likely to be rehospitalized during the follow-up period in 1997 • than during the follow-up periods in the pre-fire years of 1995 or 1996.

• The survival functions of the exposed cohorts resumed similar trajectories to unexposed cohorts during the post-fire period of November 1, 1997 to December 31, 1998.

• Source: Mott JA, Mannino DM, Alverson CJ, Kiyu A, Hashim J, Lee Tzesan, Falter K, Redd SC. Cardiorespiratory hospitalizations associated with smoke exposure during the 1997 Southeast Asian forest fires. Int. J. Hyg. Environ. Health 208(2005) 75-85 99 Findings of the study

• Communities exposed to forest fire smoke during the Southeast Asian forest fires of 1997 • experienced short-term increases in cardiorespiratory hospitalizations.

• When an air quality emergency is anticipated, • persons over age 65 with histories of respiratory hospitalizations • should be pre-identified from existing hospitalization records and • given priority access to interventions

• Monday 19 September 2016 07.56 • Harvard and Columbia universities estimate tens of thousands of premature deaths in areas closest to blazes clearing forest and peatland • They estimated there were 91,600 premature deaths in Indonesia, 6,500 in Malaysia and 2,200 in Singapore. • https://www.theguardian.com/world/2016/sep/19/haze-indonesia-forest-fires-killed-100000-people-harvard-study

A MI-17 helicopter run by the Indonesian National Disaster Mitigation Agency water-bombs a fire in South Sumatra province. Photograph: Abdul Qodir/AFP/Getty Images. Agence France-Presse 101 VIRUS INFECTIONS

102 VIRUS INFECTIONS Hand, Foot and Mouth Diseases

103 Hand, Foot and Mouth Disease (HFMD)

104 Selected Publications on HFMD relating to Sarawak

• Isolation of Subgenus B Adenovirus During a Fatal Outbreak of Enterovirus 71- Associated Hand, Foot, and Mouth Disease in Sibu, Sarawak. • M Jane Cardosa, Shekhar Krishnan, Phaik Hooi Tio, David Perera, See Chang Wong. Lancet. 1999 Sep 18; 354(9183):987-91. Full text link: http://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(98)11032-2.pdf

• Deaths of Children during an Outbreak of Hand, Foot, and Mouth Disease in Sarawak, Malaysia: Clinical and Pathological Characteristics of the Disease. • Chan LG, Parashar UD, Lye MS, Ong FG, Zaki SR, Alexander JP, Ho KK, Han LL, Pallansch MA, Suleiman AB, Jegathesan M, Anderson LJ. Clin Infect Dis. 2000 Sep; 31(3):678-83. Full text link: http://cid.oxfordjournals.org/content/31/3/678.long

• Adenovirus type 21-associated acute flaccid paralysis during an outbreak of hand-foot- and-mouth disease in Sarawak, Malaysia. • Ooi MH, Wong SC, Clear D, Perera D, Krishnan S, Preston T, Tio PH, Willison HJ, Tedman B, Kneen R,Cardosa MJ, Solomon T. Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America [2003, 36(5):550-559]

• A human adenovirus species B subtype 21a associated with severe pneumonia. • Elias Hage, Daniela Huzly, Tina Ganzenmueller, Robert Beck, Thomas F. Schulz, Albert Heim. 105 Journal of Infection (2014) 69, 490e499 http://dx.doi.org/10.1016/j.jinf.2014.06.015 Kiyu A, Ooi MH, Perera D, Cardosa MJ and Ong FGL (2015). “Enterovirus Diseases” In: Heymann DL (Ed.) Control of Communicable Diseases Manual (20th edition), pp 190-196. Washington DC: American Public Health Association.

106 1.0. INTRODUCTION

Hand, foot and mouth disease (HFMD) • a common acute viral illness that primarily affects infants and young children, • often occurs in clusters or outbreaks. • major causative agents of HFMD are: • coxsackievirus A16 (CVA16), • human enterovirus 71 (HEV71) and • coxsackievirus A10 (CVA10) • of the genus Enterovirus in the family

Picornaviridae. uchukeling.com/.../uploads/Picture2.jpg

109 Asia-Pacific Countries Affected By EV71 Epidemics Since 1997

Japan (1997,2000,2003) Korea (2000) China (2007, 2008) Taiwan (1998, 2000, 2004, 2009) Vietnam (2005, 2007, 2008) Sarawak, MY (1997, 2000, 2003, 2006) Singapore (2000, 2003, 2006, 2008) Australia (Perth) (1999)

110 Large Outbreaks Caused By EV71 Has Increased Since 1997

1997 Outbreak in Sarawak began in early April 1997; From 1 June through 30 August 1997: • 2628 cases were reported; • 889 children were hospitalized for observation; • 39 patients had aseptic meningitis or acute flaccid paralysis; • 29 died 1997: smaller outbreaks in Peninsular Malaysia & Singapore 1998: Taiwan (estimated that there were more than one million cases) 1999: Perth, Australia (Same EV71 virus as in Sarawak 1997) 2000, 2003, Sarawak and 2006 (over 13,000 cases were reported in the 2006 outbreak). 2008 China (6,300 cases and 26 deaths till 4 May 2008) 111 HFMD Sentinel data: 1998 - 2008

Outbreaks Due to EV71 in Sarawak Occur Every Three Years

HFMD SENTINEL CASES 1998-2008

300

250

200

150

CASES

100

98-1 98-9 99-4 00-7 01-2 02-5 03-8 04-3 05-6 08-2

98-17 98-25 98-33 98-41 98-49 99-12 99-20 99-28 99-36 99-44 99-52 00-15 00-23 00-31 00-39 00-47 01-10 01-18 01-26 01-34 01-42 01-50 02-13 02-21 02-29 02-37 02-45 02-53 03-16 03-24 03-32 03-40 03-48 04-11 04-19 04-27 04-35 04-43 04-51 05-14 05-22 05-30 05-38 05-46 06-02 06-10 06-18 06-26 06-34 06-42 06-50 07-06 07-14 07-22 07-30 07-38 07-46 08-10 08-18

EPID WEEK

EV71 in Sarawak from 1998-2008

160

140

120

100

EV71 POS EV71 60

Jul-98 Jul-99 Jul-00 Jul-01 Jul-02 Jul-03 Jul-04 Jul-05 Jul-06 Jul-07

Jan-98 Jan-99 Jan-00 Jan-01 Jan-02 Jan-03 Jan-04 Jan-05 Jan-06 Jan-07 Jan-08

Mar-98 Mar-99 Mar-00 Mar-01 Mar-02 Mar-03 Mar-04 Mar-05 Mar-06 Mar-07 Mar-08

Sep-98 Nov-98 Sep-99 Nov-99 Sep-00 Nov-00 Sep-01 Nov-01 Sep-02 Nov-02 Sep-03 Nov-03 Sep-04 Nov-04 Sep-05 Nov-05 Sep-06 Nov-06 Sep-07 Nov-07

May-98 May-99 May-00 May-01 May-02 May-03 May-04 May-05 May-06 May-07 MONTH-YR 112 Source: Prof Jane Cardosa What Is Known About HFMD

EV71 is not the only virus associated with HFMD • Other viruses include Coxsackievirus A16, Coxsackievirus A10, etc • Only EV71 causes very large outbreaks.

113 Many non-EV71 enteroviruses cocirculate pre and post outbreak

Long tail of 2000 outbreak in Sarawak due to HFMD outbreak in Johor and Singapore and parents bring children to clinics

114 Different Enteroviruses Predominate at Different Times

115 GENOGROUP B IN BORNEO/SINGAPORE; GENOGROUP C IN CHINA/VIETNAM

Different sub-genogroups appear in different outbreak years 117 EV71 GENOTYPES ISOLATED

118 VIRUS INFECTIONS Japanese Encephalitis

120 Japanese Encephalitis in Sarawak

• Simpson DI, Bowen ET, Platt GS et al. (1970) • Japanese encephalitis in Sarawak: virus isolation and serology in a Land Dyak village. Transactions of the Royal Society of Tropical Medicine and Hygiene 64, 503–510. • Simpson DI, Bowen ET, Way HJ et al. (1974) • Arbovirus infections in Sarawak, October 1968–February 1970: Japanese encephalitis virus isolations from mosquitoes. Annals of Tropical Medicine and Parasitology 68, 393–404. • Simpson DI, Smith CE, Marshall TF et al. (1976)

• Arbovirus infections in Sarawak: the role of the domestic pig. Transactions of the Royal Society of Tropical Medicine and Hygiene 70, 66–72.

• In 1997, a pilot hospital-based surveillance study for JE was set up in Sibu Hospital in Sarawak, followed in 1998 by passive surveillance for all other hospitals in the state.

121 Japanese encephalitis (JE) admissions in Sibu Hospital between 1997 and 2006.

Using leftover (surplus) vaccines ordered during the Nipah outbreak in 1998-1999

The bars represent the number of JE admissions in Sibu Hospital by quarter of the year over the 10-year study period, 1997–2006 (Q1 = January–March, Q2 = April–June, Q3 = July–September, Q4 = October–December).

Source: Wong SC, Ooi MH, Abdullah AR, Wong SY, Shekhar K, Tio PH, Pek PC, Lai BF, Anand M, Muhi J, Kiyu A, Arif MT and Cardosa MJ. A decade of Japanese encephalitis surveillance in Sarawak, Malaysia: 1997–2006. Tropical Medicine and International Health. volume 13 no 1 pp 52–55 January 2008 122 Effect of JE Vaccination in Sarawak

• Pre JE Vaccination: • the average annual incidence of JEV was 9.8 per 100 000 population under 12 years, • Post JE Vaccination • The average annual incidence of JEV dropped to 4.3 per 100 000 population under 12 years.

123 VIRUS INFECTIONS Dengue, Chikungunya, Zika

124 Dengue - updates

125 SYLVATIC DENGUE

Fever from the forest: prospects for the continued emergence of sylvatic dengue virus and its impact on public health

• Nikos Vasilakis*, Jane Cardosa‡, Kathryn A. Hanley§, Edward C. Holmes∥,¶, and Scott C. Weaver* • *Department of Pathology, Center for Biodefense and Emerging Infectious Disease, Institute for Human Infection and Immunity, and Center for Tropical Diseases, University of Texas Medical Branch, Galveston, Texas 77555, USA • ‡Institute of Health and Community Medicine, Universiti Sarawak Malaysia (UNIMAS), 94300 Kota Samarahan, Sarawak, Malaysia • §Department of Biology, New Mexico State University, Las Cruces, New Mexico 88003, USA • ∥Center for Infectious Disease Dynamics, Department of Biology, Mueller Laboratory, The • Pennsylvania State University, University Park, Pennsylvania 16802, USA • ¶Fogarty International Center, National Institutes of Health, Bethesda, Maryland 20892, USA

• Nat Rev Microbiol. 2011 Jun 13;9(7):532-41. doi: 10.1038/nrmicro2595.

126 First New Dengue Virus Type in 50 Years http://news.sciencemag.org/health/2013/10/first-new-dengue-virus-type-50-years?rss=1

• By chance, researchers screening dengue viral samples found a virus collected during an outbreak in Malaysia's Sarawak state in 2007 that they suspected was different from the four original serotypes. • They sequenced the virus and found that it is phylogenetically distinct from the other four types. • "We discovered and characterized a new dengue serotype," announced Nikos Vasilakis, a virologist at University of Texas Medical Branch in Galveston, here today at the Third International Conference on Dengue and Dengue Haemorrhagic Fever. • Vasilakis suspects that it is circulating, possibly among macaques, in the forests of Sarawak

• Science. 2013 Oct 25;342(6157):415. doi: 10.1126/science.342.6157.415. Tropical medicine. Surprising new dengue virus throws a spanner in disease control efforts. Normile D. • The Third International Conference on Dengue and Dengue Hemorrhagic Fever 2013 (Dengue 2013) will be held on 21-23 October 2013 at The Imperial Queen’s Park Hotel in Bangkok, Thailand. The theme of this conference is “Global Dengue: Challenges and Promises”. 128 Bilangan Kes Demam Denggi di Sarawak yang Dilaporkan dari ME 01/2013 sehingga ME 39/2016 120

100

40 Bil. Kes Bil. Paras Epidemik Paras Amaran 30 22 20 17

0 1 6 11 16 21 26 31 36 41 46 51 4 9 14 19 24 29 34 39 44 49 1 6 11 16 21 26 31 36 41 46 51 4 9 14 19 24 29 34 39 2015 2016 2013 2014 Minggu Epid

350 Tren Kumulatif Kes Denggi Bagi Negeri Sarawak Dari Minggu Epid 1, Tahun 2007 Sehingga Minggu Epid 39, Tahun 2016 300

250

200

150 Jumlah KesJumlah 100

0 1 13 25 37 49 9 21 33 45 5 17 29 41 1 13 25 37 49 9 21 33 45 5 17 29 41 1 13 25 37 49 9 21 33 45 5 17 29 41 53 12 24 36 129 2007 2008 2009 2010 Minggu2011 Epid 2012 2013 2014 2015 2016 Chikungunya

130 Geographic distribution and spread of Chikungunya virus (CHIKV) and its two urban vectors, A. aegypti and A. albopictus (1958-2014).

Lark L. Coffey, Anna-Bella Failloux and Scott C. Weaver. Chikungunya Virus–Vector Interactions Viruses 2014, 6(11), 4628-4663; doi:10.3390/v6114628 131 http://www.mdpi.com/viruses/viruses-06-04628/article_deploy/html/images/viruses-06-04628-g001-1024.png Chikungunya Virus in Sarawak – Since the 1960s

(Kpg. Tijirak, 19th mile Kuching/Serian Rd.)

Abstract • 449 human sera collected in a Land Dyak village were tested for antibodies to 11 arboviruses. • Japanese encephalitis and dengue virus antibodies were particularly prevalent. • The rates of infection with these viruses were estimated to be 5.2% per annum for Japanese encephalitis, 8.8% for dengue 1 and 4.3% for dengue 2. • Chikungunya virus antibodies were quite common with an annual infection rate of the order of 5% per annum. • Infections with other Group A and B and Bunyamwera group viruses were generally at a low level. 132 Chikungunya outbreak 2009 - Affected Kampongs

• From 26.3.2009 to 10.6. 2009 • 8 localities • 356 cases

Distance to each localities and mode of transportation from Betong Health Office: 1. Betong__74km__Pusa___Ferry(15min)___Beladin___8km___Semarang ___15km____Maludam 2. Pusa______45 minutes by boat______Medang 3. Betong______96km______Tuie (halfway is unpaved oil palm road) 133 A Fatal Case of Chikungunya Virus Infection with Liver Involvement

H H Chua, K Abdul Rashid, W C Law, A Hamizah, Y K Chem, A H Khairul, K B Chua, Med J Malaysia Vol 65 No 1 March 2010

“In the present on-going large outbreak due to chikungunya virus of Central/East African genotype, a previous healthy sixty six years gentleman without co- morbidity was noted to have severe systemic infection by the virus and involvement of his liver.

He subsequently passed away due to cardiovascular collapse after 5 days of illness”

Source: Med J Malaysia Vol 65 No 1 March 2010. http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.443.902&rep=rep1&type=pdf 134 Zika Virus

135 Publications on Zika virus in Malaysia

• Marchette NJ, Garcia R, Rudnick A. 1969. Isolation of Zika virus from Aedes aegypti mosquitoes in Malaysia (Bentong Pahang). Am J Trop Med Hyg. 1969 May;18(3):411-5 • Wolfe ND, Kilbourn AM, Karesh WB, Rahman HA, Bosi EJ, Cropp BC, Andau M, Spielman A, Gubler DJ. 2001. Sylvatic transmission of arboviruses among Bornean orangutans. Am J Trop Med Hyg 64:310 –316. • Kilbourn AM, Karesh WB, Wolfe ND, Bosi EJ, Cook RA, Andau M. 2003. Health evaluation of free-ranging and semi-captive orangutans (Pongo pygmaeus pygmaeus) in Sabah, Malaysia. J Wildl Dis 39:73–83. http://dx.doi.org/10.7589/0090-3558- 39.1.73.

136 Seroprevalence to flaviruses among orangutans and humans in Sabah, 1996–1997

Percent and number positive to Dengue-2 Japanese Zika Tembusu Langat Encephalitis Orangutans % No. + to % No. + to % No. + to % No. + % No. + to to Wild 28 11/40 38 15/40 13 5/40 3 1/39 0 0/40 (from Eastern Sabah) Semi-captive 32 10/31 16 5/31 3 1/31 3 1/29 3 1/31 (from Sepilok)

Humans Native Bornean 37 11/30 40 12/30 30 9/30 4 1/25 0 0/31 Migrants 74 59/80 29 24/83 49 40/81 4 3/73 1 1/83 Total 50 91/181 30 56/184 30 55/182 4 6/166 1 2/184

Adult humans, classified as either native-born Bornean or non-native-born Bornean (migrants),who lived or worked on the boundaries of the Sepilok Forest Reserve.

Wolfe ND, Kilbourn AM, Karesh WB, Rahman HA, Bosi EJ, Cropp BC, Andau M, Spielman A, Gubler DJ. 2001. Sylvatic transmission of arboviruses 137 among Bornean orangutans. Am J Trop Med Hyg 64:310 –316. Seroprevalence to flaviruses among orangutans and humans in Sabah, 1996–1997

Percent and number positive to Dengue-2 Japanese Zika Tembusu Langat Encephalitis Age range (yr) % No. + to % No. + to % No. + to % No. + % No. + to to 21–30 33 1/3 67 2/3 33 1/3 0 0/3 0 0/3 31–40 24 4/17 41 7/17 35 6/17 7 1/14 0 0/18 ≥ 40 60 6/10 30 3/10 20 2/10 0 0/80 10 1/10 Total 37 11/30 40 12/30 30 9/30 4 1/25 3 1/31

Adult humans, classified as either native-born Bornean or non-native-born Bornean (migrants),who lived or worked on the boundaries of the Sepilok Forest Reserve.

Wolfe ND, Kilbourn AM, Karesh WB, Rahman HA, Bosi EJ, Cropp BC, Andau M, Spielman A, Gubler DJ. 2001. Sylvatic transmission of arboviruses 138 among Bornean orangutans. Am J Trop Med Hyg 64:310 –316. Zika Virus in Africa and Asia

1947 Virus first isolated in from a rhesus monkey in the Zika Forest of Uganda, Africa 1968 isolated for the first time from humans in Nigeria. From human infection was reported from other 1951 African countries such as Uganda, Tanzania, through Egypt, Central African Republic, Sierra Leone 1981 and Gabon in parts of Asia including India, Malaysia, the Philippines, Thailand, Vietnam and Indonesia https://en.wikipedia.org/wiki/Zika_virus 139 First outbreak of Zika virus outside Africa and Asia

2007 The first outbreak of the disease outside of (April) Africa and Asia on the island of Yap in the Federated States of Micronesia 2013- outbreaks in French Polynesia, New Caledonia 2014 and other Pacific Island Countries 2015 A larger outbreak of Zika virus outside Africa (April) and Asia was confirmed in Brazil.

https://en.wikipedia.org/wiki/Zika_virus 140 Phylogenetic tree of ZIKV showing the African and Asian lineages, including the strains that recently emerged in the Pacific and Brazil

141 Musso D, Gubler DJ. 2016. Zika virus. Clin Microbiol Rev 29:487–524. doi:10.1128/CMR.00072-15 Acute Zika Virus Infection (in a 45 year-old woman in Heidelberg, Germany), after Travel to Malaysian Borneo, September 2014

Fever started 6 days after returning from Sabah

8-24 August 2014 In Sabah

2014 142 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 21, No. 2, February 2015 Acute Zika Virus Infection (in a 45 year-old woman in Heidelberg, Germany), after Travel to Malaysian Borneo, September 2014

• Map of northern Borneo showing the itinerary through the Malaysian state of Sabah of a patient with Zika fever. • The patient most likely became infected while staying in Keningau and southern villages (Papalungan), where she also took a boat trip on the Sungai Papalungan, a river through the rain forest

Tappe D, Nachtigall S, Kapaun A, Schnitzler P, Günther S, Schmidt-Chanasit J. Acute Zika virus infection after travel to Malaysian Borneo, September 2014143 [letter]. Emerg Infect Dis. 2015 May [date cited]. http://dx.doi.org/10.3201/eid2105.141960. DOI: 10.3201/eid2105.141960 No need to press panic button

From left: Dr Andrew, Dr Jamilah, Dr Sim, Dr Chua, and Dr Lee showing posters on eliminating breeding places of mosquitoes during the press conference. Dr Sim says Zika virus not spread by passive contact, can be contained by destroying mosquito breeding places September 15, 2016, Thursday Daryll Law [email protected] 144 http://www.theborneopost.com/2016/09/15/no-need-to-press-panic-button/ BACTERIAL INFECTIONS

145 BACTERIAL INFECTIONS Cholera

146 Selected publications on Cholera in Sarawak

• Cholera in Sarawak: A Historical Perspective (1873-1989)

• H Yadav, Chai Meng Chee. Med. J. Malaysia Vol. 45 No. 3 Sept. 1990 • Detection of Vibrio Cholerae from Aquatic Environment in Sarawak

• Norazah A, Zainuldin MT, Kamel AG, Kamaliah MN, Taha AM. Medical Journal of Malaysia 2001, Vol 56 No1 Mar 2001:4-9 • Prevalence of Potentially Pathogenic Vibrio Species in the Seafood Marketed in Malaysia

• Elhadi N, Radu S, Chen CH, Nishibuchi M. J Food Prot. 2004 Jul; 67(7):1469-75 • Factors Associated with Emergence and Spread of Cholera Epidemics and Its Control in Sarawak, Malaysia between 1994 and 2003

• Benjamin Patrick Guda, Gunsalam Jurin Wolmon, Radu Son, Napis Suhaimi, Fatimah Abu Bakar, Beon Meting, Benjamin Adom, Dumba Clement William, Sengol Selvanesan, Mansur Faizul, Jeffrey Rody Nakaguchi Yoshitsugu, Nishibuchi Mitsuaki. The Southeast Asian studies 43(2), 109-140, 2005-09 • Genomic Diversity of Cholera Outbreak Strains in East Malaysia

• Lesley Maurice Bilung, Yong Sy Fuh, Velnetti Linang, Adom Benjamin, Micky Vincent, Kasing Apun, Samuel Lihan, Chien Su Lin. Malaysian Journal of Medicine and Health Sciences (ISSN 1675-8544); Vol. 10 (2) June 2014: 19-26

147 History of Cholera in Sarawak

• Cholera has been in existence in Sarawak for many years. • The concept of illness and injury among the Sea Dayaks is closely linked with religion and magic • Cholera to the Sea Dayak is the coming of a great spirit from the sea to kill and eat.

• H Yadav, Chai Meng Chee. Cholera in Sarawak: A Historical Perspective (1873-1989) . Med. J. Malaysia Vol. 45 No. 3 Sept. 1990

• Roth HL. The Natives of Sarawak and British North Borneo, 1968, Vol. 1 & 2. University of Malaya Press, Kuala Lumpur. (originally published in 1886)

149 The Seven Cholera Pandemics

1817-1824 The first known cholera pandemic originated in the Ganges River Delta, India, with the disease outbreak occurring in Calcutta

1829-1849 Similar to the first, the second cholera pandemic began with outbreaks along the Ganges River Delta, and from here the disease spread along trade routes to cover most of India 1852-1860 The third cholera pandemic is widely considered as the most deadly and again had its origins in India 1863-1875 The fourth pandemic began in the Bengal region of India, where Indian Muslim pilgrims visiting Mecca spread the disease to the Middle East 1881-1896 Again originating in the Bengal Region of India, the fifth cholera pandemic spread throughout Asia, Africa, South America and parts of France and Germany 1899-1923 The sixth pandemic again originated in India, killing more than 800,000 and spread rapidly to the Middle East, North Africa, Eastern Europe and Russia 1961-Present The seventh pandemic originated in Indonesia and is still occurring today. The disease spread through Asia and the Middle East until it reached Africa in 1971 https://sites.google.com/site/waterrediseasecholera/the-seven-pandemics 150 History of Cholera in Sarawak

1873 • an epidemic of cholera occurred in Sarawak • impossible to say how many died. 1873 • on board the vessel S.S. 'Hydaspes' (14th Oct) between Aden and Suez the only son and daughter of H.H. the Raja of Sarawak died. • Although the cause of the deaths were not confirmed, cholera was not ruled out. H Yadav, Chai Meng Chee. Cholera in Sarawak: A Historical Perspective (1873-1989) . Med. J. Malaysia Vol. 45 No. 3 Sept. 1990 151 Cholera Epidemic June 1902

• At this time an expedition had been organised to punish a group of Dayaks living in the interior of Simanggang District who were attacking and killing friendly neighbours. • A force of some 12,000 loyal Dayaks including some Malays were assembled, and the expedition moved up the Batang Lupar to Simanggang in about 800 boats. • On leaving Simanggang, all appeared well, but when the expedition proceeded some distance up the river, cholera broke out and spread rapidly. • There were 1,000 deaths in the force (8.3%) which eventually had to retire without accomplishing its mission. • The surviving sick and healthy members dispersed to their respective longhouses and villages. • The outbreak started on about 10th June and lasted until 29th June.

• Source: Report on the Cholera Outbreak in Sarawak 1961, 1963, Government Printers Office, Kuching. • Cited in: H Yadav, Chai Meng Chee. Cholera in Sarawak: A Historical Perspective (1873-1989) . Med. J. Malaysia Vol. 45 No. 3 Sept. 1990 152 Cholera Epidemic June 1902

• The report stated that the Batang Lupar was polluted with corpses and shields of members of the expedition. • Cases of cholera thus appeared in several other areas and these were attributed to the dispersal of Dayaks after the break-up of the expeditionary force. • Divisions I, II, III and IV had cases of cholera. • The disease also occurred in Kuching town in a sporadic form during the months of June and July. • Overall this epidemic caused about 1,500 deaths but the number of cases was unknown.

153 154 Cholera Vibrios in seafood

155 Prevalence of Potentially Pathogenic Vibrio Species in the Seafood Marketed in Malaysia

Seafood samples obtained in seafood markets and supermarkets at 11 sites selected from four states in Malaysia were examined for the presence of nine potentially pathogenic species from the genus Vibrio between July 1998 and June 1999. • Examined 768 sample sets that included shrimp, squid, crab, cockles, and mussels. • Eight potentially pathogenic Vibrio species were detected, • with overall incidence in the samples • V. cholera 4.6% , • V. parahaemolyticus 4.7% , • V. vulnificus 6.0% • V. alginolyticus 11% , V. metschnikovii 9.9% , V. mimicus 1.3% , V. damsel 13% , V. fluvialis 7.6% , • combined population of all of the above 52% .

• Elhadi N, Radu S, Chen CH, Nishibuchi M. Prevalence of Potentially Pathogenic Vibrio Species in the Seafood Marketed in 156 Malaysia. J Food Prot. 2004 Jul; 67(7):1469-75 Prevalence of Potentially Pathogenic Vibrio Species in the Seafood Marketed in Malaysia

• As many as eight Vibrio species were detected in shrimp and only four in squid and peel mussels. • The overall percent incidence of any of the eight vibrios was highest (82%) in cockles (Anadara granosa) among the seafoods examined and was highest (100%) in Kuching, Sarawak • Of 97 strains of V. cholerae isolated, one strain belonged to the O1 serotype and 14 to the O139 serotype. • The results indicate that the various seafood markets in Malaysia are contaminated with potentially pathogenic http://previews.123rf.com/images/cao nzeper/caonzeper1405/caonzeper1405 Vibrio species regardless of the season and 00022/39617571-Fresh-Blood-cockle- shell-at-the-market-Stock-Photo.jpg • suggest that there is a need for adequate consumer protection measures.

• Elhadi N, Radu S, Chen CH, Nishibuchi M. Prevalence of Potentially Pathogenic Vibrio Species in the Seafood Marketed in Malaysia. J Food Prot. 2004 Jul; 67(7):1469-75

157 Cholera outbreaks in Sarawak in recent years

Bintulu 2012 • 110 confirmed cases • 63 were asymptomatic • 22of the asymptomatic cases were food handlers

Limbang 2016 • two waves of outbreaks, from 3.3 to 17.6.2016 • 56 confirmed cholera cases of serotype Ogawa • First wave (6 weeks) • 16 cases, 6 localities • Second wave (8 weeks) • 40 cases; 17 localities.

158 Bintulu Regatta Camp site (on the opposite side of Bintulu town) from where cholera spread 2012-07-23

159 Hanging latrine next to Bintulu Regatta Camp site, at high tide, 2012-07-23

160 The period of Bazaar Ramadan made the control of cholera outbreak in Bintulu in July 2012, even more challenging

161 Kampong Limpaku Pinang, Limbang – where a cholera outbreak occurred in 2016

162 Kampong Limpaku Pinang, Limbang – where a cholera outbreak occurred in 2016

163 Rain water catchment system, Kampong Limpaku Pinang, Limbang. It was dry as there was no rain for a few months

164 BACTERIAL INFECTIONS Leptospirosis

165 Selected publications on Leptospirosis

• Leptospirosis in the Rejang Basin • Suut L, Yusof H, Arif MT, Rahim NA, Katip JT, Suhaili MR. Asia Research News,18 May 2012, page 29. Full text link: http://issuu.com/asiaresearchnews/docs/final_rseanews2012 /29 • Serological and Molecular Detection of Leptospira Spp. From Small Wild Mammals Captured in Sarawak, Malaysia. • Thayaparan S, Robertson ID and Abdullah MT. • Malaysian Journal of Microbiology, Vol 11(1) 2015, pp. 93-101

166 Leptospirosis in Humans in Rejang River Basin area

• 31 per cent of humans sampled were infected • an association between certain daily activities, including farming and water activities with leptospirosis infection

• Source: Suut L, Yusof H, Arif MT, Rahim NA, Katip JT, Suhaili MR. Leptospirosis in the Rejang Basin. Asia Research News,18 May 2012, page 29. Full text link: http://issuu.com/asiaresearchnews/docs/final_rseanews2012/29

167 Leptospirosis in small mammals in Sarawak

The samples of blood and kidneys of small rodents, bats and squirrels from 5 localities were analyzed. Blood samples Kidney samples • 47.0% (73/155) wild small animals • 11.0% (17/155 individual animals) had antibodies to different serovars positive for Leptospira on a of leptospires molecular study Seroprevalence rate for: Positive results were from • Rats: 57.9%; • Plantain squirrels: 53%; • Squirrels: 42.9%; • Müller’s rat: 35%; • Bats: 40%; • Brown spiny rats: 12%;

Source: Thayaparan S, Robertson ID and Abdullah MT. Serological and Molecular Detection of Leptospira Spp. From Small Wild Mammals Captured in Sarawak, Malaysia. Malaysian Journal of Microbiology, Vol 11(1) 2015, pp. 93-101

Plantain Squirrel (Callosciurus notatus) Rajah Spiny Rat Muller's giant Sunda rat 168 by BoonHong Chan (or Brown Spiny Rat) BACTERIAL INFECTIONS Melioidosis

169 Bakun Hydroelectric Dam, Belaga District, Sarawak

The 2,400MW Bakun hydroelectric dam. http://www.mysarawak.org/2011/06/06/score-growth-story- begins-to-unwrap-with-upcoming-commissioning-of- bakun-dam-latest.html http://www.theborneopost.com/2010/10/08/water- impoundment-in-bakun-dam-on-sunday/attachment/2193/ Fast facts: • second highest concrete faced rockfill dam in the world. • Bakun dam is 207 metres high • Reservoir surface area of nearly 70,000 hectares, about the size of Singapore. • The main civil works began in 2002. • A workforce of just over 3000 are on site at the peak of construction activity. 170 • Source: http://www.bakundam.com/home.html Bakun islands to be tourism draw Borneo Post 15 December 2011, p11, col. 1-5

• More than 10 major islands will become permanent features of the Bakun hydroelectric dam area covering an area almost the size of Singapore.

171 Burkholderia pseudomallei

http://latimicrolancewheeler.wikispaces.c om/History+of+burkholderia+pseudomall ei+and+melioidosis

172 Don’t laugh off the spirits —Dr Elli

• by Zoee Hillson [email protected]. Posted on August 10, 2011, Wednesday

• KUCHING: The belief that deaths in Murum and Bakun area were caused by angry ancestral spirits should not be laughed off because it is part of the anthropological culture of the community there.

• Bakun Community Safety Committee (BCSC) chairman Dr Elli Luhat said

• “Although I myself as a field scientist do not believe in ghosts and angry spirits, it does not mean I have to rule out their anthropological belief.

• http://www.theborneopost.com/2011/08/10/don%E2%80%99t-laugh-off-the-spirits-%E2%80%94dr-elli/

173 Selected Publications on Melioidosis related to Sarawak

• Seroepidemiology of Melioidosis among the Indigenous Communities and Environmental Surveillance for Burkholderia Species in the Periphery of Loagan Bunut National Park, Sarawak • Abdul Karim Russ Hassan, Timothy John Jay Inglis, Iswandy Ibrahim, Savithri Devi Puthucheary, Hashami Bohari. Malaysian Journal of Public Health Medicine, (Vol. 4) Supplement 1, 2004. SA2SP2 • Reliability of Automated Biochemical Identification of Burkholderia Pseudomallei is Regionally Dependent • Yuwana Podin, Mirjam Kaestli, Nicole McMahon, Jann Hennessy, Hie-Ung Ngian, Jin-Shyan Wong, Anand Mohana, See-Chang Wong, Timothy William, Mark Mayo, Robert W. Baird, Bart J. Currie. J. Clin. Microbiol. September 2013 vol. 51 no. 9: 3076-3078 • Burkholderia pseudomallei Isolates from Sarawak, Malaysian Borneo, Are Predominantly Susceptible to Aminoglycosides and Macrolides • Yuwana Podin, Derek S. Sarovich, Erin P. Price, Mirjam Kaestli, Mark Mayo, King-Ching Hii, Hie-Ung Ngian, See-Chang Wong, Ing-Tien Wong, Jin-Shyan Wong, Anand Mohan, Mong-How Ooi, Tem-Lom Fam, Jack Wong, Apichai Tuanyok, Paul Keim, Philip M. Giffard, and Bart J. Currie. Antimicrob Agents Chemother. 2014 Jan; 58(1): 162–166.

174 PARASITIC INFECTIONS

175 PARASITIC INFECTIONS Malaria

176 Malaria in Sarawak and Brunei (1956) Population of Sarawak

JULIAN DE ZULUETA. MALARIA IN SARAWAK AND BRUNEI. Bull. Wld Hlth Org. 1956, 15, 651-671 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2538283/pdf/bullwho00533-0281.pdf

177 Malaria in Sarawak and Brunei (1956) Malaria Endemicity • Most of the information was collected between July and December 1952, but a few records from 1953 have also been included. • Surprising finding: • The data show that in most places comparatively low spleen- and parasite rates were found • 92% of the people live in hypoendemic areas, • where the spleen-rate in children 2-9 years old is below 10%. • 8% of the population living in highly malarious or hyperendemic areas, • where the spleen-rate in children 2-9 years of age is above 50%

• JULIAN DE ZULUETA. MALARIA IN SARAWAK AND BRUNEI. Bull. Wld Hlth Org. 1956, 15, 651-671. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2538283/pdf/bullwho00533-0281.pdf 178 Malaria Prevalence In Sarawak And Brunei, Based On Results Of 1952-53 Survey

JULIAN DE ZULUETA. MALARIA IN SARAWAK AND BRUNEI. Bull. Wld Hlth Org. 1956, 15, 651-671. 179 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2538283/pdf/bullwho00533-0281.pdf Patrick T. O’Shaughnessy. PARACHUTING CATS AND CRUSHED EGGS: The Controversy Over the Use of DDT to Control Malaria. (Am J Public Health. 180 2008;98: 1940–1948. doi:10.2105/ AJPH.2007.122523) Tom Harrisson with a native of Sarawak, Indonesia, in 1945. The longhouse at Bario, Sarawak in 1959. Source. Tom Harrisson, World Source. Tom Harrisson, World Within: A Borneo Story (London: Cresset Within: A Borneo Story (London: Cresset Press, 1959). Used with Press, 1959). Used with permission from Oxford University permission from Oxford University Press (China) Press (China) Ltd (On 25 March 1945, he was parachuted with seven Z Force operatives from a Consolidated Liberator onto a high plateau occupied by the Kelabit people.) 181 Source: Patrick T. O’Shaughnessy. PARACHUTING CATS AND CRUSHED EGGS: The Controversy Over the Use of DDT to Control Malaria. (Am J Public Health. 2008;98: 1940–1948. doi:10.2105/ AJPH.2007.122523) A Sarawak Malaria Eradication Project worker spraying a longhouse in 1962. 182 Source: Heritage in Health:The Story of Medical and Health Care Services in Sarawak . Sarawak Health Department, 2012. p184 DDT, Thatched Roofs, Parachuting Cats

• “In the early 1950s, there was an outbreak of a serious disease called malaria among the Dayak people in Borneo. • The World Health Organization tried to solve the problem. • They sprayed large amounts of a chemical called DDT to kill the mosquitoes that carried the malaria. • The mosquitoes died and there was less malaria. • That was good”

Patrick T. O’Shaughnessy. PARACHUTING CATS AND CRUSHED EGGS: The Controversy Over the Use of DDT to Control Malaria. (Am J Public Health. 2008;98:183 1940–1948. doi:10.2105/ AJPH.2007.122523) DDT, Thatched Roofs, Parachuting Cats

• “However, there were side effects. • One of the first effects was that the roofs of people’s houses began to fall down on their heads. • It turned out that the DDT was also killing a parasitic wasp that ate thatch-eating caterpillars. • Without the wasps to eat them, there were more and more thatch-eating caterpillars. • Worse than that, the insects that died from being poisoned by DDT were eaten by gecko lizards, which were then eaten by cats. • The cats started to die, the rats flourished, and the people were threatened by outbreaks of two new serious diseases carried by the rats, sylvatic plague and typhus. • To cope with these problems, which it had itself created, the World Health Organization had to parachute live cats into Borneo”

Patrick T. O’Shaughnessy. PARACHUTING CATS AND CRUSHED EGGS: The Controversy Over the Use of DDT to Control Malaria. (Am J Public Health. 2008;98:184 1940–1948. doi:10.2105/ AJPH.2007.122523) http://images.slideplayer.com/28/9293725/slides/slide_7.jpg 185 186 http://images.slideplayer.com/25/8017782/slides/slide_14.jpg Marabunta or Spider Wasp (Family Pompilidae) solitary wasp at nest in thatched roof

187 http://l7.alamy.com/zooms/54235025248e467c9de573997d5affd6/marabunta-or-spider-wasp-family-pompilidae-solitary-wasp-at-nest-in-cc4yya.jpg Interesting references

43. Tom Harrisson, “Operation Cat Drop,” Animals 5 (1965): 512–513. . . . 53. “RAF to ’Chute 2 Cats Into Jungle to Fight Rats,” New York Times, June 22, 1954: 59; Peter White, “The Fur Is Flying,” The New York Times, May 22, 1955: 56. 54. Royal Air Force, “Operations Record Book,” report of Beverley Flight of 48th Squadron, March 1960, Changi, Singapore, compiled by Flying Officer Humphrey. 55. The drop also included “4 cartons of stout for a recuperating chieftain”!

• Patrick T. O’Shaughnessy. PARACHUTING CATS AND CRUSHED EGGS: The Controversy Over the Use of DDT to Control Malaria. (Am J Public Health. 2008;98: 1940–1948. doi:10.2105/ AJPH.2007.122523)

188 Plasmodium knowlesi or Monkey malaria

189 History of discovery of 5 species of malaria parasites

• 1900 (116 years ago) • Plasmodium vivax, • P. falciparum, and • P. malariae were discovered

• 1918 • P. ovale discovered • 2010 • P. ovale was shown by genetic methods to consist of two subspecies, P. ovale curtisi and P. ovale wallikeri.

• Francis EG Cox. History of the discovery of the malaria parasites and their vectors. Cox Parasites & Vectors 2010, 3:5 http://www.parasitesandvectors.com/content/3/1/5 • https://en.wikipedia.org/wiki/Plasmodium_knowlesi • Lee K.S.; Cox-Singh J.; Brooke G.; Matusop A.; Singh B (2009). "Plasmodium knowlesi from archival blood films: Further evidence that human infections are widely distributed and not newly emergent in Malaysian Borneo". Int J Parasitol. 39 (10): 1125–1128. 190 doi:10.1016/j.ijpara.2009.03.003. PMC 2722692 History of discovery of Plasmodium knowlesi

1927 Giuseppe Franchini (an Italian) probably the first person to see P. knowlesi (≈ 90 years when he was examining the blood of Macaca fascicularis (long-tailed macaque) ago) 1932 • Robert Knowles and Das Gupta described the species in detail; (≈ 85 years • showed that it could be transmitted to man by blood passage; ago) • but failed to name it. • Sinton and Mulligan named the parasite after Dr Knowles. 1930s From early in the, P. knowlesi was used as a pyretic agent for the treatment of to 1955 patients with neurosyphilis. 1957 Garnham et al. suggested that P. knowlesi could be the fifth species capable (≈ 60 years of causing endemic malaria in humans. ago) 1965 the first case of a naturally occurring infection of knowlesi malaria in humans (≈ 50 years was reported in an American man who had returned after working in the ago) jungle in peninsular Malaysia.

• Francis EG Cox. History of the discovery of the malaria parasites and their vectors. Cox Parasites & Vectors 2010, 3:5 http://www.parasitesandvectors.com/content/3/1/5 • https://en.wikipedia.org/wiki/Plasmodium_knowlesi • Lee K.S.; Cox-Singh J.; Brooke G.; Matusop A.; Singh B (2009). "Plasmodium knowlesi from archival blood films: Further evidence that human infections are widely distributed and not newly emergent in Malaysian Borneo". Int J Parasitol. 39 (10): 1125–1128. doi:10.1016/j.ijpara.2009.03.003. PMC 2722692 191 History of discovery of malaria parasite Plasmodium knowlesi

2004: First report showing that • there is a fifth species (now sixth) of Plasmodium causing human malaria • cases are being misdiagnosed due to the morphological similarity between P. knowlesi and P. malariae • Discovery made possible due to the development of molecular detection assays which could differentiate between Plasmodium knowlesi and the morphologically similar Plasmodium malariae • Work with archival samples has shown that infection with this parasite has occurred in Malaysia at least since the 1990s • now (2004) known to cause 70% of the malaria cases in certain areas of Sarawak • Lee K.S.; Cox-Singh J.; Brooke G.; Matusop A.; Singh B (2009). "Plasmodium knowlesi from archival blood films: Further evidence that human infections are widely distributed and not newly emergent in Malaysian Borneo". Int J Parasitol. 39 (10): 1125–1128. doi:10.1016/j.ijpara.2009.03.003. PMC 2722692 • Singh, B., Lee, K.S., Matusop, A., Radhakrishnan, A., Shamsul, S.S.G., Cox-Singh, J., Thomas, A.W. & Conway, D. (2004) A large focus of naturally acquired Plasmodium knowlesi infections in human beings. The Lancet, 363, 1017-1024.

192 Typical morphology of erythrocytic stages of Plasmodium knowlesi, P. falciparum and P. malariae Lee KS, Cox-Singh J, Singh B. Morphological features and differential counts of Plasmodium knowlesi parasites in naturally acquired human infections. Malar J 2009 ; 8 : 73

http://www.jle.com/e-docs/00/04/83/A8/texte_alt_jlemst0116gr2.jpg 193 Man, Monkeys, Mosquitoes, Malaria

The founding director of the Malaria Research Centre (MRC) Unimas, Professor Balbir Singh.

Anopheles albimanus mosquito feeding on a human arm – this mosquito is a vector of malaria, and mosquito control is a very effective way of reducing the incidence of malaria.

https://upload.wikimedia.org/wikipedia/commons/a/ae/Anopheles_albim anus_mosquito.jpg

Long-tailed macaques play a good host to the fifth malarial strain known to affect humans – P knowlesi.

http://seeds.theborneopost.com/2016/08/18/malaria-man-monkeys- 194 and-mosquitoes-oh-my/ https://contagions.files.wordpress.com/2015/01/map.jpg . Source: Singh, B., & Daneshvar, C. (2013). Human Infections and Detection of Plasmodium knowlesi195 . Clinical Microbiology Reviews, 26(2), 165–184. doi:10.1128/CMR.00079-12 Malaria cases by Epidemiology Week in Sarawak from Epid. Week 1/2011 to Epid. 120 Week 39/2016

100 the red line indicate number of P. knowlesi cases 80

60 BilanganKes 40

0 1 1121314151 9 19293949 7 17273747 5 15253545 2 12223242521020304050 2011 2012 2013 2014 2015 2016 Tahun 196 CANCERS

197 Selected Publications on Cancers in Sarawak

• Nasopharyngeal Cancer in Sarawak (Borneo) • By C.S MUIR (Singapore) and W.F OAKLEY (Kuching). J Laryngol Otol. 1967 Feb;81(2):197-207. • Epidemiology of Cancer in Sarawak • Dawie Usop AK (Kiyu, A). The Southeast Asian Journal of Tropical Medicine and Public Health [1985, 16(4):584-590] • Clinical Presentation of Nasopharyngeal Carcinoma in Sarawak Malaysia • T S Tiong & K S Selva. Med J Malaysia Vol 60 No 5 December 2005 • What Doctors Know About Cancer Pain Management: An Exploratory Study in Sarawak, Malaysia • Devi BC, Tang TS, Corbex M. J Pain Palliat Care Pharmacother. 2006; 20(2):15-22 • Reducing by Half the Percentage of Late-State Presentation for Breast and Cervix Cancer Over 4 Years: A Pilot Study of Clinical Down Staging in Sarawak, Malaysia • Devi BC, Tang TS, Corbex M. Ann Oncol. 2007 Jul; 18(7):1172-6. Epub 2007 Apr 13.

198 Selected Publications on Cancers in Sarawak

• Head and Neck Cancer: Possible Causes for Delay in Diagnosis and Treatment • Lee SC, Tang IP, Avatar SP, Ahmad N, Selva KS, Tay KK, Vikneswaran T, Tan TY. Med J Malaysia. 2011 Jun; 66(2):101-4. • Acral Melanoma of The Extremities: A Study of 33 Cases Sarawakian Patients • Zainal AI, Zulkarnaen M, Norlida DK, Syed Alwi SA. Med J Malaysia. 2012 Feb; 67(1):60-5. • Incidence and Risk Factors for Breast Cancer Subtypes in Three Distinct South- East Asian Ethnic Groups: Chinese, Malay and Natives of Sarawak, Malaysia • C.R. Beena Devi, Tieng Swee Tang and Marilys Corbex. Int J Cancer. 2012 Dec 15; 131(12):2869-77. doi: 10.1002/ijc.27527. Epub 2012 Mar 29. • Brain and Spinal Tumour • Goh CH, Lu YY, Lau BL, Wong JOL, Lee HK, Liew D, Wong A. Med J Malaysia. 2014 Dec; 69(6):261-7

199 Epidemiology of Cancer in Sarawak 1981-1982 based on histopathology records in the Central Medical Laboratory, Kuching, Sarawak, in 1981 and 1982. • 8,219 patients from whom biopsies were taken • 485 from whom marrow biopsies were taken. • Out of these, 1,326 (15%) were reported malignant. most common cancer sites among most common cancer sites among males were: females were: 1. lymph nodes, 1. breast, 2. nasopharynx, 2. cervix and 3. skin and 3. lymph nodes 4. stomach,

Dawie Usop AK (Kiyu, A). Epidemiology of Cancer in Sarawak. The Southeast Asian Journal of Tropical Medicine and Public Health [1985, 16(4):584-590] 200 Common cancers by ethnic groups in Sarawak 1981-1982

Race Male Female Chinese Nasopharynx Breast Sea Dayaks Lymph nodes Cervix Malays Skin cancers Land Dayaks Nasopharyngeal

• The pattern of cancers has not changed much since 1966 • The findings of the present study are very similar to the series from the Institute of Medical Research, Kuala Lumpur, in 1969 to 1971. Dawie Usop AK (Kiyu, A). Epidemiology of Cancer in Sarawak. The Southeast Asian Journal of Tropical Medicine and Public Health [1985, 16(4):584-590] 201 Annual Age-standardised-rates per 100,000 for 10 leading cancer sites in males by ethnicity, Sarawak, 2001-2005

Sites Ethnic Groups Iban Chinese Malay Bidayuh Melanau Trachea, bronchus, lung 18.9 19.6 18.3 22.1 6.4 Nasophayrnx 13.8 12.7 7.7 30.4 4.5 Colorectal 8.1 24.8 11.5 10.7 3.6 Stomach 11.8 10.2 8.2 14.2 2.0 Lymphoma 6.0 6.8 7.4 13.3 3.9 Liver 6.4 8.6 6.7 10.2 4.3 Leukemia 3.4 5.0 5.7 3.9 2.4 Prostate 3.8 9.7 5.4 4.1 0.9 Skin (including melanoma) 4.5 5.6 5.4 4.1 3.2 Bladder 2.9 5.7 3.0 3.1 1.6

Ooi CH, Mastulu W. Epidemiology of cancer in Sarawak, 2001-2005. Sarawak Health Department. p17 202 Annual Age-standardised-rates per 100,000 for 10 leading cancer sites in females by ethnicity, Sarawak, 2001-2005

Sites Ethnic Groups Iban Chinese Malay Bidayuh Melanau Breast 8.0 29.9 24.6 8.3 4.9 Cervix 16.0 13.6 11.2 13.1 8.2 Colorectal 5.5 22.3 7.7 9.7 3.2 Trachea, Bronchus, Lung 8.8 9.0 7.7 8.5 3.9 Ovary 6.4 7.8 7.1 6.8 4.2 Nasopharynx 5.9 4.2 3.2 15.0 1.5 Stomach 5.3 6.5 4.3 12.5 3.3 Lymphoma 5.0 4.1 4.5 7.0 2.0 Leukemia 3.4 3.4 4.1 2.3 2.0 Corpus Uteri 3.3 5.2 3.9 3.1 4.0

Ooi CH, Mastulu W. Epidemiology of cancer in Sarawak, 2001-2005. Sarawak Health Department. p17 203 CARDIOVASCULAR RESEARCH

204 More than 40 research publications on CVD by authors from Sarawak

• Use of 64-row MDCT and Syngo Circulation as an Objective Coronary Imaging Tool Before Percutaneous Coronary Stenting. • Chin BSP, Ong TK, Seyfarth T, Ang CK, Liew CK, Chan WL, Annuar R, Liew HB, Fong AYY, Chin WM, Sim KH. Int J Cardiovasc Imaging 2006;22:S1-18.

• A novel approach to identifying culprit lesions in acute coronary syndrome by multidetector computed tomography. • Chin SP, Ong TK, Liew CK, Chan WL, Liew HB, Annuar R, Ang CK, Fong A, Sim KH. Vessel density ratio: [2914-121] J Am Coll Cardiol. 2006;47(4):25B.

205 More than 40 research publications on CVD by authors from Sarawak

• Carotid intima media thickness and high sensitivity C-reactive protein as markers of cardiovascular risk in a Malaysian population. • Chua SK, Kilung A, Ong TK, Fong AY, Yew KL, Khiew NZ, Nor Hanim MA, Tan SK, Cham YL, Asri S, Sim KH. Med J Malaysia. 2014 Aug;69(4):166-74.

• Prevalence of asymptomatic atrial fibrillation in Malaysian patients with hypertension. • Wong JS, B R, A F, I R, Fong AY. Med J Malaysia. 2013 Apr;68(2):141-3

• Early detection of C-reactive protein and von Willebrand factor levels in Malaysian patients with acute coronary syndrome. • Tiong WN, Sim EUH, Fong AYY, Ong TK. Journal of Cardiovascular Disease Research 2013 Mar, 4(1):3-6.

• Cytochrome P450 2C19 polymorphism and platelet aggregation in clopidogrel- treated patients among Malaysian multiethnic population. • Tiong WN, Fong AYY, Hwang SS, Wee CC, Mejin M, Ong TK. Heart 2012;98:E270.

206 ESOTERICA

207 ESOTERICA Injury by Durian fruit

208 Penetrating Ocular Injury by Durian Fruit S. Aziz, T. Asokumaran, G. Intan, http://www.e-mjm.org/2009/v64n3/Penetrating_Ocular_Injury.pdf

After surgical repair; Marks of The durian fruit with its spines durian spines can be seen on the patient’s face. The cornea appeared hazy with no view of the iris and the posterior segment due to hyphema. Note: the patient lost vision in the affected eye and four months after the initial injury, ocular prosthesis fitting was done for cosmetic reason. Advice: wear a crash helmet when collecting durian. 209 ESOTERICA Jering poisoning

210 Acute Anuric Renal Failure Following Jering Bean Ingestion Jin Shyan Wong, Teng-Aik Ong, Hock-Hin Chua and Clare Tan, ASIAN JOURNAL OF SURGERY VOL 30 • NO 1 • JANUARY 2007 http://www.e-asianjournalsurgery.com/article/S1015- 9584%2809%2960134-2/pdf

https://upload.wikimedia.org/wikipedia/commons/b/b3/Jeri ng_Archidendron_pauciflorum.JPG http://mysarawak2.blogspot.my/2013/06/the-jering-tree.html

211 Urinary system

212 http://www.philipcaruso-story.com/wp-content/uploads/2016/03/Ureteral-obstruction.png Acute Anuric Renal Failure Following Jering Bean Ingestion

• Djenkol bean or jering (Pithecellobium jeringa) • Jering contains 1-2% djenkolic acid, a sulfur-containing amino acid • A healthy 45-year-old man presented with • colicky left loin pain, • dysuria, • frank haematuria and • foul smelling urine a day after ingesting jering. • He developed oliguria and was anuric by the 3rd day • Jin Shyan Wong, Teng-Aik Ong, Hock-Hin Chua and Clare Tan. Acute Anuric Renal Failure Following Jering Bean Ingestion. ASIAN JOURNAL OF SURGERY VOL 30 • NO 1 • JANUARY 2007 http://www.e-asianjournalsurgery.com/article/S1015-9584%2809%2960134-2/pdf 213 Acute Anuric Renal Failure Following Jering Bean Ingestion

• Initially, he was treated with intravenous hydration and frusemide, but urine output remained poor. • Serum creatinine increased from 176 to 848 μmol/L over 3 days. • Hence, urgent bilateral ureteric stenting was done, and thick “tomato sauce” sludge was found. • The patient subsequently had good diuresis after the procedure. • The stents were removed 4 days later.

• Jin Shyan Wong, Teng-Aik Ong, Hock-Hin Chua and Clare Tan. Acute Anuric Renal Failure Following Jering Bean Ingestion. ASIAN JOURNAL OF SURGERY VOL 30 • NO 1 • JANUARY 2007 http://www.e-asianjournalsurgery.com/article/S1015-9584%2809%2960134-2/pdf 214 ESOTERICA Pufferfish (Ikan Buntal) poisoning

215 Case Report – Pufferfish Poisonings in Malaysia

• Pufferfish is not considered as “a delicacy” in Malaysia except in Betong, a district in Sarawak where various dishes of yellow pufferfish are consumed by the local community. • ikan buntal kuning (Xenopterus naritus), this species of pufferfish is found in abundance along the Batang (River) Saribas in Betong, Sarawak • Although rarely occurs, 4 cases of pufferfish poisonings with 5 fatalities were reported recently. Two of them took place in the peninsula, one in Sabah, one in Sarawak. • Two deaths were reported upon consumption of salted pufferfish roes. • It was reported that the victims purchased the salted pufferfish roes from a shop in a village in Saratok. Department of Health in Saratok took immediate action to confiscate and ban further selling of pufferfish products in that area. • When screened, the salted eggs samples were found to contain high concentration of tetrodotoxin. • Razak Hj Lajis, Che Nin Man, Nurjuliana Mohd Noor, Sazaroni Md. Rashid National Poison Centre, University Sains Malaysia, 11800 Minden, Penang 216 http://www.asiatox.org/8APAMT%20PP/PP60_Pufferfish%20Poisonings%20in%20Malaysia.pdf 217 http://bombasticborneo.com/wp-content/uploads/2011/08/spaoh02.jpg Sri Aman pufferfish versus Japan’s Fugu

S a k a i D a n a: Another Weekend In Bandar Sri Aman. sakaidana.blogspot.com https://www.google.com/search?q=puffer+fish+preparation+Sarawak&client=firefox- b&biw=1900&bih=905&source=lnms&tbm=isch&sa=X&ved=0ahUKEwiz5Pyc4r7PAhVIpY 8KHQ1_AdEQ_AUIBygC#tbm=isch&q=puffer+fish+betong+market&imgrc=5VhBsP3JxrKe kM%3A

Preparing fugu, Japan's poisonous fish dish 218 18 May 2012 http://www.bbc.com/news/magazine-18102811 ESOTERICA Tapioca poisoning

219 http://1.bp.blogspot.com/_PY- http://www.punmiris.com/himg/o.15935.jpg tSKGwF0g/TQo8_LIwA4I/AAAAAAAAABs/fYCCV3EF1vE/s1600/tapioca.jpg

https://kinghatfood.files.wordpress.com/2016/04/20160402_0840001.jpg https://upload.wikimedia.org/wikipedia/commons/ 220 0/0a/Tapioca.jpg Acute cassava poisoning in children in (Marudi) Sarawak Dr S. S. Cheok TROPICAL DOCTOR, 1978,8,99-101

Tapioca, (Manihot utilissima), • contains several alkaloids, • the poisonous substance is hydrocyanic or prussic acid (15 to 28 ppm). • Acute poisoning presents with nausea, vomiting, abdominal distension, cyanosis, dyspnoea, apathy, collapse and death.

• Of the two children, • one developed more severe symptoms • since she ate more of the tapioca cake and • possibly the child's high gastric acid content resulted in increased hydrolysis of linamarin and free HCN. • The patients responded to administration of sodium thiosulphate,

221 ESOTERICA Palang

222 The “PALANG”, its History and Proto-History in West Borneo and the Philippines. Tom Harrisson. Journal of the Malaysian Branch of the Royal Asiatic Society. Vol. 37, No. 2 (206) (November, 1964), pp. 162-174

Borneo Palang types in Method of old Kayan palang operation (reconstructed)223 Tom Harrisson’s collection Photos of Instruments used for inserting Palang (he instruments belonged to an old Kenyah man in Lio Mato in 1986)

Left: Coconut husk used to protect the sharpness of a sharpened iron nail in Bamboo slivers to squeeze the glans penis Top: How the hole is made through the glans penis 224 THE “PALANG”: II. Three further notes. Tom Harrisson. Journal of the Malaysian Branch of the Royal Asiatic Society. Vol. 39, No. 1 (209) (July, 1966), pp. 172-174

Plate III. Calcinated encrusted mass on palang operated from an Iban male, 1964. The ends of the metal penis-bar just show at the top and bottom left. Scale in millimetres.

225 Modern Penile Implants

• Bolitas culture: Penile implants and the Filipino male ego!, • by Kate Natividad. August 11, 2013 • http://getrealphilippines.com/blog/2013/08/bolitas-culture-penile- implants-and-the-filipino-male-ego/

• Penile Implants among (Australian) Prisoners—A Cause for Concern? •Lorraine Yap , Tony Butler, Juliet Richters, Eva Malacova, Handan Wand, Anthony M. A. Smith, Luke Grant, Alun Richards, Basil Donovan. •PLOS 1. Published: January 11, 2013. DOI: 10.1371/journal.pone.0053065 •http://journals.plos.org/plosone/article?id=10.1371/journal.pone. 0053065

226 PLANTS

227 PLANTS Bintangor Tree and Calanolides

228 Bintangor tree

The Bintangor tree, which produces a compound that fights HIV. Pharmaceuticals replicated the compound in the lab to avoid having to harvest rainforest trees. Photo: Dr. Doel Saejarto. Courtesy of Sarawak MediChem Pharmaceuticals http://www.terracompr.com/Projects/advancedlife.html

This bintangor tree (Calophyllum sp.) has been tapped and the sap collected to investigate its medicinal properties, including potential AIDS treatment. Photographed in Kubah National Park, Sarawak, Malaysian Borneo. Credit: W K Fletcher. http://www.gettyimages.com/detail/photo/this- 229 bintangor-tree-has-been-tapped-and-the-high-res-stock- photography/128573937 Selected Publications on Calanolide A related to Sarawak

• Antiviral Activity and Mechanism of Action of Calanolide A Against the Human Immunodeficiency Virus Type-1 • Currens MJ, Gulakowski RJ, Mariner JM, Moran RA, Buckheit RW Jr, Gustafson KR, McMahon JB, Boyd MR. J Pharmacol Exp Ther. 1996 Nov; 279(2):645-51. • Sensitivity and Resistance To (+)-Calanolide A of Wild-Type and Mutated Forms of HIV-1 Reverse Transcriptase • Quan Y, Motakis D, Buckheit R Jr, Xu ZQ, Flavin MT, Parniak MA, Wainberg MA. Antivir Ther. 1999; 4(4):203-9 • Calanolides, the Naturally Occurring Anti-HIV Agents • Xu ZQ, Flavin MT, Jenta TR. Curr Opin Drug Discov Devel. 2000 Mar; 3(2):155-66

230 PLANTS Sarawak Biodiversity Centre

231 Sarawak Biodiversity Centre

232 Sarawak Biodiversity Centre https://www.google.com/maps 233 Selected Publications Related to Medicinal Plants from Sarawak

• Photodynamic Activity of Plant Extracts from Sarawak, Borneo • Wan Wui Jong, Pei Jean Tan, Fadzly Adzhar Kamarulzaman, Michele Mejin, Diana Lim, Ida Ang, Margarita Naming, Tiong Chia Yeo, Anthony Siong Hock Ho, Soo Hwang Teo, and Hong Boon Lee. Chemistry & Biodiversity – Vol. 10 (2013) • Identification of Traditional Medicinal Plant Extracts With Novel Anti-Influenza Activity • Dhivya Rajasekaran, Enzo A. Palombo, Tiong Chia Yeo, Diana Lim Siok Ley, Chu Lee Tu, Francois Malherbe, Lara Grollo. PLoS One. 2013 Nov 27;8(11):e79293. • Comparative Antimicrobial Activity of South East Asian Plants Used in Bornean Folkloric Medicine • Savithri Galappathie, Enzo A. Palombo, Tiong Chia Yeo, Diana Lim Siok Ley, Chu Lee Tu, Francois M. Malherbe, Peter J. Mahon. Journal of Herbal Medicine 4 (2014): 96–105 • Building a Discovery Partnership with Sarawak Biodiversity Centre: A Gateway to Access Natural Products from the Rainforests • Tiong Chia Yeo, Margarita Naming and Rita Manurung. Comb Chem High Throughput Screen. 2014 Mar; 17(3):192-200.

234 Medicinal plants used as indigenous herbal medicines that showed the highest antimicrobial activities

Fibraurea tinctoria Pyrenaria jonquieriana Baccaurea lanceolata

Goniothalamus tapisoides Polyalthia hookeriana

Savithri Galappathie, Enzo A. Palombo, Tiong Chia Yeo, Diana Lim Siok Ley, Chu Lee Tu, Francois M. Malherbe, Peter J. Mahon. 236 Comparative Antimicrobial Activity of South East Asian Plants Used in Bornean Folkloric Medicine. Journal of Herbal Medicine 4 (2014): 96–105 CLINICAL RESEARCH CENTRES

237 Clinical Trials

• The global market for clinical trials • estimated to reach USD14.2 billion in 2016 • projected to reach USD22 billion by 2021

• In Asia, • the growth rate has outpaced the rest of the world • approximately 30% year-on-year growth.

238 Setting up Clinical Research Centres (CRC) to seize the opportunities in Clinical Research

• clinical research as part of national healthcare National Key Economic Areas. • Many facilities and much resources have been made available by the Ministry of Health, over the last 10 years. • CRCs function as the clinical research arm of the Ministry of Health • It currently has 33 branches located at major Ministry of Health hospitals; • three are based in Sarawak, namely • CRC Sarawak General Hospital • CRC Sibu hospital and • CRC Miri Hospital.

239 Performance of CRCs in Sarawak

• In 2015, Sarawak General Hospital was the most active CRC with 34 trials followed by Kuala Lumpur General Hospital. • It shows that Sarawak Health Department staff is fast becoming well-known to be actively engaging in research. • There were 123 publications by Malaysian CRC staff in 2015, • with 20% published in Tier 1 (top 25% of the journal impact factor distribution) and • 88% appeared in international journals including the New England Journal of Medicine and the American College of Cardiology. • Many of the publications were contributed by researchers from Sarawak.

240 New CRC Building at Sarawak General Hospital

241 Summary of clinical trial phases

Phase Primary Goal Dose Preclinical Testing of drug in non-human subjects, to unrestricted gather efficacy, toxicity and pharmacokinetic information Phase 0 Pharmacokinetics particularly oral Very small, sub- bioavailability and half-life of the drug therapeutic Phase I Testing of drug on healthy volunteers for dose- Often sub-therapeutic, ranging but with ascending doses Phase II Testing of drug on patients to assess efficacy Therapeutic dose and safety Phase III Testing of drugs on patients to assess efficacy, Therapeutic dose effectiveness and safety Phase IV Postmarketing surveillance – watching drug use Therapeutic dose in public

242 Penans of Ba’ Ajeng, near Lio Mato, Baram. Sunday, 6 April 1986 243 Katibas River, somewhere above Song, c2000 244