Transcript N. meningitidis C - The University of Sydney

The Fifty Year Revolution in
Global Public Health
Sir Gustav Nossal
Department of Pathology
The University of Melbourne
Victoria, Australia
50th Anniversary Lecture, The Medical Foundation,
The University of Sydney
30 July 2008
Major Currents are Sweeping Through the
Development Aid Field
• In July 2005, the G8 group of nations committed themselves
to a new moral imperative: get rid of extreme poverty in the
world; double aid to Africa.
• With the exception of a few countries, academic and other
leaders in developing countries are now ready for true
partnerships.
• Civil society must hold politicians to their promises. G8
already falling behind.
The Moral Imperative of Poverty Reduction
“Our policy is directed not against any country or doctrine
but against hunger, poverty, desperation and chaos. There’s
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 (today’s
equivalent $500 billion/year).
“Make Poverty History”
Bono and Bob Geldof, July 2005
The Need is for a New Global Marshall Plan
• THE WORLD CAN EASILY AFFORD 0.7% GDP FOR AID
2008 World
2008 E.U.
2008 U.S.A.
2008 Arab League
GDP :
GDP :
GDP :
GDP :
$60.1 Trillion, Growth 5% p.a.
$18.5 Trillion
$14.2 Trillion
$1.8 Trillion
• 0.7% of GDP for “richer” countries would be $280 billion. Current
ODA is $105 billion. OECD average is 0.3% of GDP. Norway
(0.9%), Sweden (0.9%), Luxembourg (0.9%), Netherlands (0.8%)
and Denmark (0.8%) only countries above 0.7%. U.S.A. 0.2%,
Australia 0.3% – plans to go to 0.5% by 2015.
• DISTRIBUTION NEEDS QUESTIONING: SUB-SAHARAN
AFRICA 20%, IRAQ 15%.
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.
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. It’s 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.
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
Health Progress is Possible (1)
• 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
Diarrhoea
Malaria
Measles
AIDS
1.8 million
1.6 million
780 thousand
390 thousand
290 thousand
Health Progress is Possible (2)
• Some Massive New Programmes Since 2000
- Global Fund to fight AIDS, TB and malaria (2002)
- President’s Emergency Plan for AIDS relief (2004)
- Gates Foundation Programs (Corpus $70 billion) (2000)
• Other Programmes are Getting Traction
- Polio Eradication
- Stop TB Partnership
- Malaria Control
- Iodine fortification
- Onchocerciasis Control Programme
- Elimination of Lymphatic Filariasis
- Eye Health (cataracts, trachoma)
Global Fund to Fight AIDS, TB and Malaria (As of June 2008)
•
In first 6 years of programme, U.S. $10.7 billion pledged to
136 countries.
•
1.75 million patients on HAART.
•
46 million people given HIV testing/counselling.
•
3.9 million people on TB chemotherapy.
•
59 million insecticide-impregnated bednets distributed.
•
60 million malaria treatments given.
•
7.6 million community health workers trained.
President’s Emergency Plan for AIDS Relief (As of June 2008)
•
Budget is $6 billion for 2008 targetted to 15 focus countries.
•
Funds also provided to Global Fund and malaria control.
•
3.5 million people in 2008 treated with HAART combining
both funds.
•
Goal for G8 and UN: By 2010, 100% coverage of AIDS
patients.
•
12.7 million pregnancies surveyed for prevention of mother
to child transmission, ARV prophylaxis for 1 million.
Polio Eradication is Still Problematic
• 4 Polio endemic countries:
(Cases to date 2008)
Nigeria (318)
India (275)
Pakistan (14)
Afghanistan (8)
• 6 Importation countries remain of 27 re-infected.
• Somalia now polio free; last case March 25, 2007.
• “Finishing the job of polio eradication is our best buy.
It’s WHO’s top operational priority. We must do it”
Margaret Chan,
D-G, WHO
May 2008
Stop TB Partnership (2006)
• 2 billion people infected with TB, 8.8 million new active cases
per year and 1.6 million deaths per year.
• DOTS the cornerstone. Including earlier DOTS programme,
22 million people treated since 1995 in 183 countries. Success
rates 70-80%.
• MDR: Multidrug resistance = resistance to cheaper, first-line
drugs.
• XDR: Extreme drug resistance = resistance to any
fluoroquinolone and to at least one of three injectable
second-line drugs.
Specially targetted pilot programmes addressing drug
sensitivity surveillance.
• HIV-positive people are 50 times more likely to develop active
TB in their lifetime than HIV-negative people.
Malaria
• At least 300 million attacks per year.
• At least 1 million deaths.
• Resistance to drugs; Anopheles resistance to
insecticides.
• Insecticide – impregnated bed nets (pyrethroids) at $5
each reduce malaria mortality >50% and all causes
mortality 20%.
• New drugs: “Medicines for Malaria Venture”. Publicprivate partnership 1999. Includes 39 R&D partners.
11 drugs in clinical trials; 5 are artemisinine derivatives.
Onchocerciasis Control Programme
• OCP ran from 1974 to 2002 to protect 30 million people in
11 countries of West Africa from river blindness.
• Progressed from larviciding (of Simulium damnosum) to
spraying plus ivermectin to ivermectin alone.
• Huge success, river blindness virtually eradicated,
600,000 cases of river blindness prevented, 18 million
children born spared the risk, 25 million hectares of land
rendered safe for cultivation and resettlement.
Global Alliance to Eliminate Lymphatic Filariasis
• More than 1 billion people in 80 countries live at risk of
lymphatic filariasis (elephantiasis), a parasitic infection
spread by mosquitoes. There are 120 million already
infected and 40 million significantly disfigured.
• GlaxoSmith Kline (albendazole) and Merck (ivermectin)
have pledged all the drug doses needed - valued at over
$1 billion.
• Community-wide drug treatment once per year also
dramatically and persistently reduces hookworm and
roundworm infections.
• So far, some 400 million people have been reached.
Progress of the GAVI Alliance 2000–2007
• 36.8 million extra children received standard vaccines.
• 176 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 2.9 million deaths prevented.
• Budget rising progressively to $1.5 billion/year.
• Bill Gates re his $1.5 billion donation: “My best investment ever”.
GAVI Alliance Challenges
• 26.3 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.
International Finance Facility–Immunisation
• 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 US$1 billion 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 at least $5.5 billion for
the GAVI Alliance.
• Donor countries are the U.K., France, Italy, Spain, Norway, Sweden,
South Africa and Brazil.
Advanced Market Commitments (AMCS) for Vaccines
• A new mechanism for development and subsidised purchase
of priority vaccines, including ones not yet invented.
• On 9 February 2007, Streptococcus pneumoniae was chosen
as the first target as it kills 1.6 million people annually.
• US$ 1.5 billion pledged with Italy, the U.K. and Canada
contributing the lion’s share.
• AMCS will fund research, support development, provide funds
for a sustainable supply and negotiate a reasonable price.
The Huge Success of Carbohydrate-Protein Conjugate
Vaccines Against Encapsulated Bacteria
• Virtual elimination of Hib and N. meningitidis C meningitis
in industrialized countries. Progress in Third World.
• 7-valent pneumococcal conjugate is excellent; need more
serotypes; a common protein vaccine via genome mining
would be welcome. So would one for N. meningitidis B and
non-typable Haemophilus.
• An exciting third world initiative on epidemic meningitis in
Africa.
Progress with Specific Vaccines: African Meningitis
• WHO–PATH Meningitis Vaccine Initiative on track using monovalent
Mening A conjugate.
• Production is by Serum Institute of India, Pune, in association with 2
CRO’s for technology transfer.
• 8 June 2007: 600 12-23 month old children in Mali and The Gambia
make 20 times more antibody than with unconjugated vaccine.
• Dell Foundation to fund demonstration study: Single dose all 1-29
year olds in Burkina Faso in 2009.
• $400 million will be required to immunize 350 million people in 20
other countries.
Progress with Diarrhoeal Disease Vaccines
Has Been Slower
• Two rotavirus vaccines licensed but expensive. Hope for a
cheaper product from the virus’s Australian discoverers.
• Good vaccines exist against cholera and typhoid but are
not being used sufficiently.
• Pre-clinical work for shigellosis and enterotoxigenic E. coli
is promising but clinical trials are lagging.
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.
Progress with the “Big 3” Vaccines –
Malaria
• GSK sporozoite vaccine RTS, S with AS02D adjuvant shown
to be safe and immunogenic in children and infants in
Mozambique in Phase II trials.
• Per cent efficacy and duration of protection remain problems
with this vaccine.
• Two studies of blood stage antigen AMA-1 are in Phase I
clinical trial.
• Steve Hoffman’s live, attenuated, mosquito salivary glandderived vaccine (Sanaria) 90% effective in human volunteers
for 4 years. Clinical trials are planned for late 2008.
Progress with “the Big 3” Vaccines –
Tuberculosis
• September 2007 Aeras Tuberculosis Vaccine Foundation
receives $200 million from Gates Foundation. Jerry Sadoff
co-ordinates world effort.
• Strategies include new BCG strains with genes for selected
soluble antigens; as well as novel recombinant proteins with
novel adjuvants; and also prime–boost regimens using
adenovirus 35. Promising antigens include ESAT6, Ag85B, TB
10.4 and HSP90.
• 6 Phase I studies have started or are about to start.
• 2 Phase 3 trials hoped for by late 2010.
Progress with “the Big 3” Vaccines –
HIV / AIDS (1)
• World effort in AIDS vaccine research now
US$ 800 million/year.
• Strong attempts to achieve co-ordination and collaboration.
– Gates Collaboration for AIDS Vaccine Discovery
– N.I.H. Vaccine Research Center (intramural) and
Centers for HIV/AIDS Vaccine Immunology (extramural)
– International Aids Vaccine Initiative
– Euro Vacc
– South African AIDS Vaccine Initiative
• GHAVE: The global HIV/AIDS Vaccine enterprise
(communication, knowledge management, policy development).
Progress with “the Big 3” Vaccines –
HIV / AIDS (2)
• About 30 candidates in early clinical trials.
• Merck on September 21, 2007, STOPPED its trial of
adenovirus serotype 5 with gag, pol and nef expressed
because of failure to prevent infection or to lower set
point.
• Only remaining candidate in efficacy trials:
– Sanofi-Pasteur canarypox vector with HIV inserts, boost
with Vaxgen gp120 (16,000 persons in Thailand).