Medical Research and Global Health

1
Medical Research and Global Health Reform
Sir Gustav Nossal Department of Pathology The
University of Melbourne
2008 Florey Lecture The University of
Adelaide 19 September, 2008
2
The Moral Imperative of Poverty Reduction
Our policy is directed not against any country
or doctrine but against hunger, poverty,
desperation and chaos. Theres no doubt in my
mind that the whole world hangs in the
balance. U.S. Secretary of State George C.
Marshall, 1948, commenting on the Marshall Plan
for the reconstruction of Europe which cost USA
4 of GDP for some years (todays equivalent 500
billion/year). Make Poverty History Bono and
Bob Geldof, July 2005
3
The Moral Imperative of Education

• Today, 100 million children do not go to school.

Think of the utterly unfair waste of the talents
and the potential of millions. Think of the
great music never composed, the great art never
drawn, the great science never discovered, the
great talent never realized, the marvellous
ability never unlocked, the wonderful potential
never fulfilled. Gordon Brown, U.K. Chancellor
of the Exchequer, 2006
4
The Moral Imperative of Health

• Important from a humanitarian point of view
• Important from an educational point of view
• Important from an economic point of view
• A virtuous circle unites health, education and
  economic growth
• 41 life-saving interventions would cost 40 per
  person per year and save 8 million lives per
  year
• Economic benefit would be 6 for every dollar
  spent

5
The Moral Imperative of Health (continued)

• There is absolutely no excuse for us to live on
  a planet where, at 10 cents per 100, millions of
  lives could be saved every year. Its hard to
  understand why we kill people, but absolutely
  unthinkable how we let millions of people die
  when we stand by without understanding what is in
  our own interest and moral obligation.
• Jeffrey D. Sachs, Earth Institute, Columbia
  University, 2003.
• 2006 World GDP 47 trillion 10 cents/100 47
  billion2006 U.S. Health Expenditure 2.1
  trillion2006 World Health Expenditure 5
  trillion 1 50 billion

6
The Moral Imperative of Communicable Diseases
Within health, the aid priorities should be

• Infectious Diseases
• Nutrition, especially micronutrients
• Antenatal and Obstetric Care
• Birth spacing
• Diabetes

7
Health Progress is Possible

• Deaths in children under 5 a record low in 2006,
  9.7 million versus 13 million in 1990.
• Sub-Saharan Africa 4.8 million, South Asia 3.1
  million.
• Among preventable deaths

Pneumonia 1.8 million Diarrhoea 1.6
million Malaria 780 thousand Measles 390
thousand AIDS 290 thousand
8
The Moral Imperative of the big three (AIDS,
TB, MALARIA)
HIV-AIDS

• 40 million infected, 4.3 million new cases/year
  2.9 million deaths/year

• 23 who require HAART are receiving treatment
• 20 licensed drugs in 5 classes

3 classes of reverse transcriptase
inhibitors protease inhibitors fusion and
entry inhibitors integrase inhibitors coming up

• Standard of care is triple therapy
• Adherence vitally important (once a day single
  pill)
• Treatment also impedes transmission
• Prevention of MTCT

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HIV-AIDS (continued)

• Vaginal Microbicide empowers women
• (Clinical trials Africa 2008-9)
• Vaccine still a long way away
• Gates recently gives 360 million for Global
  HIV/AIDS Vaccine Enterprise

10
Global Fund to Fight AIDS, TB and Malaria

• In first 5 years of programme, U.S. 8.4 billion
  pledged to 136 countries.
• 770,000 patients on HAART.
• 9.4 million people given HIV testing/counselling.
• 2 million people on TB chemotherapy.
• 18 million insectide-impregnated bednets
  distributed.
• 23 million malaria treatments given.

11
Presidents Emergency Plan for AIDS Relief

• President Bush requests 5.8 billion for F.Y.
  2008.
• 4.2 billion goes to HAART for 15 focus
  countries.
• Funds also provided to Global Fund and malaria
  control.
• Aim is to treat 2 million people in 2008
  combining both funds.
• Goal for G8 and UN By 2010, 100 coverage of
  AIDS patients.

12
Percentage AIDS Patients Getting HAART Varies
Widely
North Africa 5 India lt10 Russia lt10 Eas
tern Europe Central Asia 13 Sub-Saharan
Africa 23 Latin America Caribbean 75
Cuba (prevalence 0.1) Brazil (prevalence
0.3 near 100
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TUBERCULOSIS

• 2 billion people infected
• 9 million new cases per year
• 2 million deaths per year
• DOTS works reasonably well resistance to first
  line drugs a problem
• Vaccine ideas include

BCG with missing genes restored New
attenuated Mycobacterium tuberculosis Secreted
antigens (ESAT6, Ag85B, HSP90, up to 20 others)
either as subunit, or as DNA, or vectored
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MALARIA

• At least 300 million attacks per year
• At least 1 million deaths
• Resistance to drugs Anopheles resistance to
  insecticides
• Insecticide impregnated bed nets
• New drugs Medicines for Malaria 5
  artemisinine derivatives
• Vaccines

RTSS 40 effective needs blood stage as
well much research ongoing
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The Moral Imperative of Acute Respiratory
Diseases and Meningitis

• 7 to 11-valent pneumococcal conjugate vaccines
  work well but are expensive
• Genome mining to find one or more common protein
  vaccines would help greatly
• Haemophilus influenza B and Neisseria
  meningitidis C conjugate vaccines have been very
  successful
• N. meningitidis A conjugate is being trialled for
  Africa
• N. meningitidis B and non-typable Haemophilus
  require more work

16
The Moral Imperative of Diarrhoeal Diseases

• Two rotavirus vaccines have been registered and
  more are in the pipeline
• 600,000 deaths per year
• Pre-clinical vaccines for shigellosis look good
  clinical research is slow
• Good vaccines against cholera and typhoid exist
  but are not being used
• Progress with enterotoxigenic E. coli vaccine is
  fairly good

17
The Moral Imperative of Vaccines Which Prevent
Viral Causes of Cancer

• Increased use of hepatitis B vaccine through GAVI
  is heartening
• Some research progress towards a hepatitis C
  vaccine
• The human papilloma virus vaccine has been
  brilliantly successful
• For the second generation, more HPV genotypes
  will have to be included
• Plans for a Helicobacter pylori vaccine are on
  hold. Peptic ulcer disease and gastric cancer are
  very important

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Other Vaccines of the Future

• Bird Flu
• SARS
• Dengue
• Anti-terrorism
• Schistosomiasis
• Leishmaniasis
• Hookworm
• Group A streptococci
• and many many more !

19
Polio Eradication At What Cost?

• Worlds largest public health programme
• 3,400 workers (50 time on other activities)
• Budget now about US 600 million / year
• In the long term control would be more
  expensive than eradication
• Monovalent OPVs are making a contribution

20
Polio Cases to 4 September 2006 and 2007
Endemic Countries
2006
2007
Nigeria 784 175 India 258 185 Pakistan 18 12 Afgha
nistan 26 9
Reinfected Countries
20 of 26 have re-stopped transmission, rest
only a few sporadic cases. Reinfections show how
widely polio can spread.
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Progess of the GAVI Alliance 20002007

• 115 million extra children received standard
  vaccines, coverage goes from 63 to 77 in poorer
  countries.
• 138 million children received any or all of
  hepatitis B, Hib and yellow fever vaccines.
• Measles deaths reduced by 60 (aiming for 90 by
  2010).
• Estimated 2.3 million deaths prevented.
• Bill Gates re his 1.5 billion donation My best
  investment ever.

22
GAVI Alliance Challenges

• 28 million children each year still not
  immunised.
• Still 2.5 million vaccine-preventable deaths each
  year.
• Need 10 to 15 billion extra over next ten years.

23
International Finance FacilityImmunisation

• Bonds issued through the international capital
  markets guaranteeing large, immediately available
  sums and are redeemed via legally binding pledges
  from governments of donor countries.
• On 14 November, 2006 IFFIm placed US1 million 5
  year bonds at 5.2. Investors included central
  banks, major funds but also Mums and Dads.
• Over the next 10 years, IFFIm plans to raise US4
  billion for the GAVI Alliance.
• Donor countries are France, Italy, Norway, South
  Africa, Spain, Sweden and the U.K.

24
Advanced Market Commitments (AMCS) for Vaccines

• A new mechanism for development and subsidised
  purchase of priority vaccines, including ones not
  yet invented.
• On 9 February 2007, Streptococcus pneumoniae was
  chosen as the first target as it kills 1.6
  million people annually.
• US 1.5 billion pledged with Italy and the U.K.
  contributing the lions share.
• AMCS will fund research, support development,
  provide funds for a sustainable supply and
  negotiate a reasonable price.

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Progress with Specific Vaccines African
Meningitis
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Progress with Specific Vaccines Malaria

• GSK sporozoite vaccine RTS, S with AS02D adjuvant
  shown to be safe and immunogenic in children aged
  3 to 5 in Mozambique.
• Per cent efficacy and duration of protection
  remain problems with this vaccine.
• Steve Hoffmans live, attenuated, mosquito
  salivary gland-derived vaccine (Sanaria) 90
  effective in human volunteers for 4 years.
  Clinical trials are planned for 2008.

27
Progress with Specific Vaccines Tuberculosis

• Jerry Sadoff heads Aeras Tuberculosis Vaccine
  Foundation closely partnered by Crucell, The
  Netherlands, and well funded by Gates Foundation.
• Strategies include new BCG strains with genes for
  selected soluble antigens as well as novel
  recombinant proteins with novel adjuvants and
  also primeboost regimens using adenovirus 35.
• It is hoped to have six vaccine candidates in
  Stage 1 or 2 clinical trials by end 2007, two of
  which it is hoped will progress to Stage 3.
• Clinical trial sites have been identified
  prominently including South Africa.

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Progress with Specific Vaccines HIV / AIDS (1)
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Progress with Specific Vaccines HIV / AIDS (2)

• About 30 candidates in early clinical trials.
• 2 candidates in efficacy trials

Sanofi-Pasteur canarypox vector with HIV
inserts, boost with Vaxgen gp120 (16,000 persons
in Thailand). Merck replication-defective
adenovirus serotype 5 with gag, pol, nef
expressed (big problem with Ad5 pre-existent
immunity).
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Progress with Specific Vaccines HIV / AIDS (3)
Some Promising Strategies

• Mimic trimeric env. structure
• Stabilize or mimic intermediate (cross-linked
  env-CD4) in HIV binding process.
• Mimotopes of those epitopes to which broadly
  neutralizing monoclonal antibodies bind.
• New adjuvants, new prime-boost regimens.
• Shorten clinical trials by looking for what
  reduces the set point of virus load.