To conduct research likely to produce improvements in health - PowerPoint PPT Presentation

A collaboration between the Faculty of Tropical Medicine, Mahidol University and Oxford University To conduct research likely to produce improvements in health

Thailand 1979

The Wellcome Wellcome Trust Mahidol University Oxford Trust Mahidol University Oxford The Tropical Medicine Research Programme Tropical Medicine Research Programme 1979 - -86 86 1979 Malaria Rabies Snake bite Director: Professor Nick Day

Wellcome Trust Mahidol University Oxford Tropical Medicine Research Programme 1979-1986 Snake bite Malaria Rabies

Malaria 250,000,000 people infected 1-2 million deaths each year >3000 deaths / day

Defining the pathophysiology Optimising treatment

The world’ ’s most s most The world drug- -resistant malaria parasites resistant malaria parasites drug

The Wellcome Wellcome Trust Mahidol University Oxford Trust Mahidol University Oxford The Tropical Medicine Research Programme Tropical Medicine Research Programme Malaria 1986 - - 1986 Rabies Snake bite Chancroid and LGV Melioidosis Infantile beri-beri Cryptococcal meningitis Penicilliosis Leptospirosis Rickettsial infections Pneumococcal disease in infancy Avian influenza Director: Professor Nick Day

Shoklo Shoklo Malaria Malaria Research Research Unit Unit Director: Professor Francois Nosten

1995 M 25 1990 M 15 1985 Q CURE RATE (%) 1980 SP CQ 1975 100 20 80 60 40

Shoklo Malaria Malaria Shoklo Research Unit Research Unit

Qinghaosu Qinghaosu

Artemisinin derivatives are safe and highly derivatives are safe and highly Artemisinin effective in adults, children, and pregnant effective in adults, children, and pregnant women women

CURE RATE (%) 100 AM Q 80 M 25 M 15 60 SP Sustained high cure rates for 40 Sustained high cure rates for CQ 10 years and a decline decline in in 10 years and a resistance (in (in- -vitro) vitro) resistance 20 1975 1980 1985 1990 1995 2000 2005

Artemisinin Combination Treatments First-line everywhere

Clinical research in provincial hospitals Mae Sot, Ubon Ratchatani, Udon Thani

In April 1911, at this site, in the Pathology Laboratory of the Rangoon General Hospital, the disease melioidosis was first recognised by Captain A. Whitmore and Assistant Surgeon C.S.Krishnaswamy of the Indian Army Medical Service

Bacille de Whitemore

Burkholderia (formerly Pseudomonas) pseudomallei Aerobic, non-spore forming, environmental saprophyte found in wet soils in South and East Asia and Northern Australasia. Melioidosis, a “distemper of asses”, causes infections in mammals and birds

30% of the world’s population

MELIOIDOSIS UBON RATCHATANI • Most common cause of septicaemia during the rainy season • Most common cause of septicaemia in patients with diabetes, renal disease, or immunosuppression Chaowagul et al. J Infect Dis 1989; 159: 890-9

MELIOIDOSIS UBON RATCHATANI • 20% of community acquired septicaemias. • Previously 40% of deaths from community acquired septicaemia. Chaowagul et al. J Infect Dis 1989;159:890-9 Ceftazidime

Cryptococcal Meningitis Meningitis Cryptococcal Amphotericin B + 5-flucytosine

Clinical Research Unit, Clinical Research Unit, Hospital for Tropical Hospital for Tropical Diseases, Diseases, Ho Chi Minh Minh City, 1991 City, 1991 Ho Chi

Arrival January 1991 Phu Hien

Malaria Typhoid Dengue Tetanus Viral encephalitis Pyogenic meningitis Tuberculous meningitis Pneumococcal infections Avian influenza Plague Diphtheria Director; Prof Jeremy Farrar

Vaccine- -preventable diseases preventable diseases Vaccine

The genome and plasmids of Salmonella Typhi CT18 Chromosome Total size 4,809,037 bp G+C content 52.09% Coding sequences 4599 … of which pseudogenes 204 Coding density 87.6% Average gene length 958 bp rRNAs 6 x (16S -23S -5S), 1 x (16S -23S -5S -5S) tRNAs 78 Other stable RNAs 8 Active invertible sequences 2 pHCM1 pHCM2 S. Typhi CT18 was sequenced S. Typhi CT18 was sequenced at the Sanger Insitute Insitute at the Sanger

Short course fluoroquinolones Typhoid Typhoid

Dengue Dengue Randomised controlled trials of fluid resuscitation

Meningitis Meningitis

Tuberculous meningitis meningitis Tuberculous Steroids?

Japanese encephalitis Japanese encephalitis Interferon alpha-2a ineffective Raised intracranial pressure Solomon et al 2002-3

Myelitis: Acute flaccid paralysis : Acute flaccid paralysis Myelitis Polio virus Japanese encephalitis virus Solomon et al Lancet 1998; 351 : 1094-1097.

‘Flu

21,000,000 - - 40,000,000 died 40,000,000 died 21,000,000

5 9 7 8 d5 8 d7 8 d10 5/10 Oseltamivir 75mg twice daily 8/10 Methyprednisolone Mortality 8/10 Median time to death 9d (6-17)

Land area of the UK Land area of the UK Laos Laos Population ~ 6 million; 81 % rural Population ~ 6 million; 81 % rural Per capita GDP $350 pa Per capita GDP $350 pa MMR: 653/100,000 MMR: 653/100,000 IMR: 125/1,000 IMR: 125/1,000 Malaria; a major health problem Malaria; a major health problem CQ & SP; nationally recommended CQ & SP; nationally recommended antimalarials antimalarials

Wellcome Trust Mahosot Hospital Oxford Tropical Medicine Research Collaboration Director; Dr Paul Newton Malaria Malaria Causes of septicaemia Causes of septicaemia Causes of CNS infection Causes of CNS infection Typhoid Typhoid Typhus Typhus Hepatitis Hepatitis Translational research Translational research

Micronutrient deficiencies Infantile beriberi killed 7% of all infants in this refugee population 200 180 160 neonatal mortality 140 post-neonatal mortality 120 100 80 60 40 20 0 1987- 1989- 1993 1994 1995 1996 years 88 90 Luxemburger et al 2003

MAHOSOT MICROBIOLOGY REVIEW Mahosot Hospital, Vientiane, Lao PDR Issue No. 1 : February 2001 This is the first issue of a newsletter which we hope will be published every 6 months. It summarises the results of the collaborative microbiology and infectious disease research work carried out by the Wellcome Trust - – Mahosot Oxford Tropical Medicine Research Collaboration. In this issue we summarise the species of pathogens isolated from blood cultures and their drug resistance patterns. Salmonella typhi was the most common pathogen isolated from patient’s blood. However, in contrast to the situation in adjacent Viet Nam, there is little multidrug resistance (resistance to ampicillin, chloramphenicol and cotrimoxazole) Changing policy and practice

Changing antimalarial drug policy in Laos through research Feuang District Hospital Feuang District Hospital

Current treatment recommendations for Malaria Melioidosis Typhoid Dengue Diphtheria TB meningitis Cryptococcal meningitis Leptospirosis Tetanus

The strawberry plant

starts small

The strawberry plant grows and spreads if it finds fertile ground