With over 100 PPPs active in single or multiple global diseases the impact on outcome and metrics is discussed. The global impact of PPPs is difficult to evaluate due to lack of validated measurable objective parameters. Overview of rationale for PPP formation and growth is discussed. PPP provide better focus, objectives and resource mobilization and have contributed to increased R&D in tropical and neglected diseases of the poor. Disease burden of the poor and developing countries remains a major barrier to economic prosparity and global peace. The mission statements, objectives and achievements of some of these PPPs and charitable foundations are similar. It is elimination of a single or multiple diseases to increase prosperity, productivity and peace. None of the PPP is set up in countries with high disease burden. Control of high operating costs and wastage is required. In 2007 the total funding for global health was 22 billion out of which 7 billion was by PPP and foundations.
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Diffrentiation of a Cancer cell from normal one NIBIB ID 37
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Global health is derived from public health and evolved from hygiene and tropical medicine. It has become an essential component of foreign policy, a target of philanthropic action and a media darling. Global health is defined as study, research and practise on improving and equity in health for all persons worldwide.
Towards a common definition of global health
Jeffrey P Koplan , T Christopher Bond, Michael H Merson, K Srinath Reddy, Mario Henry Rodriguez, Nelson K Sewankambo, Judith N Wasserheit, for the Consortium of Universities for Global Health Executive Board‡
The Lancet, Volume 373, Issue 9679, Pages 1993 – 1995, 6 June 2009
World Health Organization WHO to tackle global health problems and eradicate diseases was formed in Geneva on 7 April, 1948 during the meeting of World Health Assembly. To raise awareness of issues of global health concern, the first World Health Day was declared on 7 April 1950.
World Health Day – 7 April 2010
Table 1. Global Burden of Disease WHO Data (updated June 2009)
Millions of patients are sick, suffering and dying while waiting for safe, affordable and effective drugs from the Industry, Research Establishment, NGO, Health Charities, Foundations, WHO and Governments.
These global citizens are tired of excuses from the healthcare establishment and international and national rulers.
Help poor patients by faster approval of new drugs, low cost manufacture and distribution of affordable drugs.
||Type and associated Diseases
||Malaria, Tuberculosis, AIDS
||Hepatitis, Leishmania, Filariasis, dengue, STD, Leprosy, Viral, bacterial and fungal infections, Drug resistance|
||Hypertension, lipid disorders, obesity
Rheumatic heart, CHF
||336||4.6||Obesity, Hypertension, Lipid disorders
Retinopathy, Foot Ulcers, Lactic acidosis, Nephropathy, Neuropathy
||Prostate, Breast, Lung, Colon
||Epilepsy, Parkinson’s disease, Depression
Alzheimer’s Disease, Schizophrenia
||Malnutrition, poor sanitation
||0.5 during childbirth
||2.7 million new cases
2200 infected persons
||Drug Resistant TB 0.44 million,
DOTS-6 m treatment costs $20, MDRTB costs $500 and 2 years to cure
India, China, Russia
WHO Map and Data Global Burden of Tuberculosis
|South Africa||460 600|
|Democratic Republic of Congo||245 330|
By mid 1970s units were formed within WHO to deal with Tropical Disease Research (TDR) , Vaccines and Child and Maternal Health. TDR initiated and started global efforts to eradicate and eliminate malaria, smallpox and tuberculosis without local input or involvement. Lack of funds and the use of low cost drug treatment led once again to failure of such campaigns and development of drug resistance. Although choroquine had become ineffective (drug resistance) it was used until 2001 because it was cheap and alternatives were more expensive. Use of artimisinin was recommended in 2001, it costs more and requires monitoring for cardiotoxicity. Ridley and Fletcher have discussed the history and achievements of TDR and how to deal with future challenges (http://www.who.int/tdr/about/pdf/nature_reviews_micro1899.pdf). TDR timelines of key achievements is available at http://www.who.int/tdr/about/pdf/anniversary_book_timeline.pdf.
Global Alliance for Vaccines and Immunization GAVI at WHO (http://www.gavialliance.org/) was launched in 2000.
. WHO Data and map : http://rbm.who.int/wmr2005/html/map1.htm
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Transmission Electron micrograph of Hepatitis B Virus CDC PHIL ID 11755
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Public Private Partnerships
The formation of TDR, GAVI and UNAIDS can be considered as the foundation and role model for Public Private Partnerships PPP advocated by healthcare charities and Jeffry Sachs of Earth Institute at Coumbia University.The rationale was that a specialist organization functioning like a virtual company model and disease focus with defined objectives and priorities It was Sachs study published in Lancet in mid 1990s that showed the lack of foreign aid money to fight AIDS in Africa was showing any reduction in mortality.
Most of these PPPs are set up in Geneva, Europe or USA and none has been set up in Africa, Asia or Latin America. The operating costs of these PPPs are relatively high and there is lot of travel (business class), 5* hotel stay, meetings, conferences, advisory boards and glossy prints out of books, monographs and papers. Thus travel and entertainment budgets are relatively high. PPPs are dependant on local third parties for execution, action, delivery and outcome measures. There is little or no attempt to discontinue or terminate projects. Projects once started continue forever. A few years ago UNAIDS wasted millions of doolars on glossy monograph to highlight the achievements of 10 years of its departing chief and founder director Peter Piot.
The following factors can derail or disrupt any disease eradication campaign
Shifting local or political priority
UNITAID’s mission is to contribute to scaling up access to treatment for HIV/AIDS, malaria and tuberculosis, primarily for people in low-income countries, by leveraging price reductions for quality diagnostics and medicines and accelerating the pace at which these are made available.
UNITAID was established to support existing efforts to achieve the United Nations Millennium Development Goals – in particular Goals 4 – Child Health, 5 – Maternal Health, 6 – Combating HIV and other diseases. UNITAID’s funds are disbursed to international partners working in global health and health commodities procurement, such as the William J. Clinton HIV/AIDS Initiative (CHAI) and UNICEF.
|POWER IN NUMBERS
UNITAID, INNOVATIVE FINANCING, AND THE QUEST FOR MASSIVE GOOD
PHILIPPE DOUSTE-BLAZY AND DANIEL ALTMAN
WITH A PREFACE BY PRESIDENT BILL CLINTON
Innovation in global health
A spoonful of ingenuity
Jan 7th 2010 | NEW YORK
From The Economist print edition
The Global Drug Facility (GDF) is a mechanism to expand access to, and availability of, high-quality anti-TB drugs and diagnostics to facilitate global DOTS expansion or maintenance to support the Stop TB Strategy.
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The Foundation for the National Institutes of Health identifies and develops opportunities for innovative public-private partnerships involving industry, academia, and the philanthropic community (www.fnih.org). There were over 100 public private partnerships funded with over $ 1 billion with over 100 active R&D projects for vaccines and drugs for tropical and neglected diseases by the end of 2008. Developments in the area of neglected diseases have opened up new opportunities for licensing by universities and companies. These public-private partnerships (PPPs) support development of drugs, vaccines and diagnostics to address diseases that predominantly afflict the poor or to make drugs available to patients in poor countries and operate on the virtual company model .
The aim is to develop biomarkers to detect and diagnose disease and monitor disease treatment and outcome. Biomarkers can be used as surrogate endpoints to gain new drug approvals. Reduction in levels of cholesterol results in reducing risk of cardiovascular deaths. Similarlarly levels of glycosylated hemoglobin HbA1c can be used to monitor efficacy of antidiabetic drugs.
The Foundation for Innovative New Diagnostics http://www.finddiagnostics.org has similar objectives (not related to NIH).
The declining R&D productivity coupled with increasing costs and reduced number of new drug approvals led to the FDA initiated CPI. The aim is to increase R&D productivity and find innovative ways to speed up introduction of safe and effective drugs. Critical Path Initiative
There is no drug to block and reverse the progression of Osteoarthritis despite advances in knowledge. Most of the treatments provide symptomatic relief. Osteoarthritis is very common disease and contributes to reduced mobility and morbidity with high economic costs. http://www.niams.nih.gov/Funding/Funded_Research/Osteoarthritis_Initiative/default.asp.
The Grand Challenge for Global Health awards grants for selected global projects. The current topics are
To develop low cost diagnostic tests, Induce mucosal immunity, develop vaccines for HIV, malaria, TB, Pneumonia, diarrrhea and new tools for eradication of malaria.http://www.gcgh.org.
The genome project is deveoted to development of all types of genomic research. http://www.genome.gov/19518664.
The Alzheimer disease Neuroimaging Initiative is to develop and validate imaging of the brain and predict disease outcome and efficacy of new drugs in clinical trials. http://www.nia.nih.gov/NewsAndEvents/PressReleases/PR20041013ADNI.htm
Pharmaceutical and biotechnology industry has no interest in developing vaccines and treatments for the tropical and neglected diseases like AIDS, Chagas’ Disease , Contraception , Dengue, Diarrhea, Leprosy, Leishmaniasis, Lymphatic filariasis, Malaria, Malaria, Onchocerciasis, Schistosomiasis , Trypanosomiasis, Tuberculosis and Sexually transmitted diseases. Because once these medicines were developed after considerable R&D expenses, international organizations were not ready to pay higher prices of new medicines. Industry was expected to donate or supply these new drugs at cost basis only. Since there was no profit or payback in such R&D, these projects were terminated. International and national organizations like WHO failed to develop new medicines for tropical diseases and lacked sufficient resources. Universities or research institutes were not able to attract interest from the industry for promising leads and companies terminated their own R&D leads because of lack of profits or commercial success. Glaxo Smith Kline and Astra Zeneca have R&D laboratories in Asia dealing with tropical diseases(outside Japan). There are no industrial R&D labs in Africa.
The 90-10% gap refers to the fact that 90% of drug discovery is directed towards diseases of the Western World with only 10% of the global disease burden. Tropical and developing and poverty related diseases accounting for 90% of world disease burden receive only 10% resources for R&D. It was noted that previous international efforts to vaccination and tropical disease eradication had failed to make any significant impact due to lack of funds, objectives and strong local opposition in some cases. Global Forum for Health Research http://www.globalforumhealth.org/Site/000
Aeras, Global TB Vaccine Foundation (Aeras) (http://aeras.org)
Tuberculosis has infected 2 billion persons worldwide and kills 1.8 million patients every year. The tB vaccine protects mainly against pediatric infections and is not effective against adult strains. Despite its widespread use, the BCG vaccine has failed to prevent the spread of the disease which infects one new victim every second. The coinfection of TB with HIV poses a new serious threat to global health. Current medicinal treatment of TB lasts 6-9 months, is considred too long by many patients who drop out or are lost to followup. These patients develop multi drug resistance which raises the cost of treatment. The need for a safer and more cost effective TB vaccine is championed by Aeras Foundation and funded by several other partners like Gates Foundation.
The widely used BCG vaccine is only effective against pediatric TB infections.The TB vaccine has no efficacy/impact on a looming TB pandemic. Co infection with HIV is even more deadly. Global Alliance for TB Drug Development (www.tballiance.org) has several projects in its R&D pipeline. However some of these projects were terminated by the industry.
Bill and Melinda Gates Foundation (www.gatesfoundation.org/GlobalHealth/InfectiousDiseases/)
The MMV was the first PPP formed in 1999 and since then has developed an R&D portfolio of over 60 projects. MMV was founded by WHO, International Federation of Pharmaceutical Manufacturers Association, IFPMA, Global Forum for Health GFHR, Rockefeller Foundation, The World Bank, ABPI, The Wellcome Trust and Swiss Agency for Development. The development of vaccine for malaria led to the formation of MVI by PATH. Malaria kills over 1 million patients each year and infects over 300-500 million persons resulting in a $12 billion loss of productivity in Afrian countries. The disease can be prevented, diagnosed rapidly and treated by insecticides spays to control mosquitos, bednets to prevent mosquito biting human victims and rapid field test for Plasmodium falciparum infections. The cheap drugs chloroquine/sulphadoxine are not effective due to drug resistance and artimisin based treatment costs much more and requires monitoring. Phase III trials with vaccine show only 30% efficacy (only 1 out of 3 person is protected by the vaccine). such a vaccine if approved can still save over 300,000 deaths each year at relativly low cost and simple treatment. there are 16 malaria vaccines in clinical trials.
At the end of World war II, the disease was endemic all over the world, it has now been eradicated in most of the Western World and over 100 countries. Development of resistance to insecticides, environmental concerns, lack of funds, political will for sustained campaign, high cost of artimisin based treatment regiment and long duration of treatment have derailed several past and current eradication campaigns.
Malaria Vaccine Initiative (MVI). (http://www.malariavaccine.org)
This is a private company based approach has resulted in marketing of some drugs in India at affordable prices has reduced the incidence of Leishmaniasis
International AIDS Vaccine Initiative (http://www.iavi.org/)
Several AIDS vaccines have failed in late stage clinical trials but there are many other candidate vaccines ready or testing.
Program for Appropriate Technology in Health http://www.path.org
The main objective is to adopt Western developed technolgy and health solution to local conditions in poor countries and make it suitable for use by local communities
International Partnership for Microbicides http://www.ipm-microbicides.org
Drugs for Neglected Diseases Initiative (www.dndi.org)
The award of the Nobel peace prize to Medicine Sans Frontier (Doctors without borders, MSF) led to the formation of this virtual PPP. The high human cost of the neglected diseases (Trypanosomiasis or sleeping sickness, Leishmaniasis, Chagas Disease and Malaria) is due to lack of new drugs to treat patients.
Médecins Sans Frontières MSF, Institut Pasteur, Indian Council of Medical Research,
Oswaldo Cruz Foundation (FIOCRUZ), TDR, and Health Ministry in Malaysia joined to develop new drugs. There were 21 projects in the R&D portfolio of DNDI.
Trypanosomiasis infects 50,000-150000 persons each year. Available treatments are costly, difficult to administer and are not effective in drug resistant strains. Another form of of Trypanosomiasis, Chagas Disease infects 8 million persons each year in Latin America. Current treatment Benznidazole (requires 60 days with 50% efficacy) and Nuffutiniox with reduced efficacy and high cost lead to bvery high drop out rates resulting in development of drug resistant parasites.
The Nippon Foundation believes in bringing together world’s wisdom to transform society and world as one family. The foundation has contributed during the past 30 years to eradicate poverty, starvation and sickness. One active recent project was to provide free drugs for leprosy in India and to raise awareness to eliminate disease based discrimination.
Rotary club has been very active through its member in campaigns for vaccination,
awareness and education in many poor or disease endemic countries.
USA Industry: Presription Drug Assistance Programs for poor and uninsured patients (https://www.pparx.org/ViewCompanies.php)
Wellcome Trust (UK) spended $ 1 billion in 2008 to promote top international and UK medical scientists and research and is Europe largest health charity. Its online e-grant system to fund research in neuroimaging, medical history and bioethics, trackdown fake antimalarials and awards to top biomedical scientists.
Aga Khan Development Network (Switzerland). http://www.akdn.org/
Aga Khan Foundation. http://www.akdn.org/akf
The Geneva based charity has been active in healthcare activities in Asia, Africa and Eastern Europe and funds universities and hospitals.
Robert Bosch Stiftung (Germany) 47 million
Provides grants in healthcare by improving healthcare delivery to low income. poor patients irrespective of race, religion and ethnic origin.
Funds innovative research in reproductive medicine
Knols on Global Health
Global Health TV Show – November 2009
Tuesday, 1st December is World Aids Day. In this special program we talk to Dr Steve Patterson from Imperial College, London about his team’s recent research in to the STEP vaccine trials in to HIV/AIDS with researchers from King’s College London and Royal Holloway, Uni. of London.