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

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

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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

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A collaboration between the Faculty of Tropical Medicine, Mahidol University and Oxford University

To conduct research likely to produce improvements in health

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Thailand 1979

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The The Wellcome Wellcome Trust Mahidol University Oxford Trust Mahidol University Oxford Tropical Medicine Research Programme Tropical Medicine Research Programme 1979 1979 -

  • 86

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Malaria Rabies Snake bite

Director: Professor Nick Day

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

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Malaria

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

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Defining the pathophysiology Optimising treatment

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The world The world’ ’s most s most drug drug-

  • resistant malaria parasites

resistant malaria parasites

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The The Wellcome Wellcome Trust Mahidol University Oxford Trust Mahidol University Oxford Tropical Medicine Research Programme Tropical Medicine Research Programme 1986 1986 -

  • Malaria

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

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Shoklo Shoklo Malaria Malaria Research Research Unit Unit

Director: Professor Francois Nosten

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1975

100 80 60 40 20

CURE RATE (%) CQ SP Q M25 M15 1980 1985 1990 1995

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Shoklo Shoklo Malaria Malaria Research Unit Research Unit

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Qinghaosu Qinghaosu

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

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1975 1980 1985 1990 1995 2000 2005 100 80 60 40 20

CURE RATE (%) CQ SP Q M25 AM M15 Sustained high cure rates for Sustained high cure rates for 10 years and a 10 years and a decline decline in in resistance resistance (in (in-

  • vitro)

vitro)

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Artemisinin Combination Treatments

First-line everywhere

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

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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

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Bacille de Whitemore

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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

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30% of the world’s population

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  • Most common cause
  • f septicaemia

during the rainy season

  • Most common cause
  • f septicaemia in

patients with diabetes, renal disease, or immunosuppression

MELIOIDOSIS

UBON RATCHATANI

Chaowagul et al. J Infect Dis 1989; 159: 890-9

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MELIOIDOSIS

  • 20% of community

acquired septicaemias.

  • Previously 40% of

deaths from community acquired septicaemia.

UBON RATCHATANI

Chaowagul et al. J Infect Dis 1989;159:890-9

Ceftazidime

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Cryptococcal Cryptococcal Meningitis Meningitis

Amphotericin B + 5-flucytosine

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

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Arrival January 1991

Hien Phu

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Malaria Typhoid Dengue Tetanus Viral encephalitis Pyogenic meningitis Tuberculous meningitis Pneumococcal infections Avian influenza Plague Diphtheria

Director; Prof Jeremy Farrar

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Vaccine Vaccine-

  • preventable diseases

preventable diseases

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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

The genome and plasmids of Salmonella Typhi CT18

  • S. Typhi CT18 was sequenced
  • S. Typhi CT18 was sequenced

at the Sanger at the Sanger Insitute Insitute

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Typhoid Typhoid

Short course fluoroquinolones

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Dengue Dengue

Randomised controlled trials of fluid resuscitation

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Meningitis Meningitis

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Tuberculous Tuberculous meningitis meningitis

Steroids?

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Japanese encephalitis Japanese encephalitis

Interferon alpha-2a ineffective Raised intracranial pressure

Solomon et al 2002-3

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Myelitis Myelitis: Acute flaccid paralysis : Acute flaccid paralysis Polio virus Japanese encephalitis virus

Solomon et al Lancet 1998;351: 1094-1097.

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‘Flu

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21,000,000 21,000,000 -

  • 40,000,000 died

40,000,000 died

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

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Laos Laos

Land area of the UK Land area of the UK 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

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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

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Micronutrient deficiencies

Infantile beriberi

killed 7% of all infants in this refugee population

Luxemburger et al 2003

20 40 60 80 100 120 140 160 180 200

1987- 88 1989- 90 1993 1994 1995 1996

neonatal mortality post-neonatal mortality

years

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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

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Feuang Feuang District Hospital District Hospital

Changing antimalarial drug policy in Laos through research

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Malaria Melioidosis Typhoid Dengue Diphtheria

TB meningitis Cryptococcal meningitis Leptospirosis Tetanus

Current treatment recommendations for

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The strawberry plant

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starts small

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The strawberry plant grows and spreads if it finds fertile ground

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