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Hard and Harder

The path to eradicating malaria in Africa involves much more than just a vaccine.

By | June 5, 2011

image: Hard and Harder Baby with malaria receiving quinine treatment in the port city of Kisumu in western Kenya.Karen Kasmauski / Corbis

Baby with malaria receiving quinine treatment in the port city of Kisumu in western Kenya. KAREN KASMAUSKI / CORBIS

Between 1955 and 1969, the Global Malaria Eradication Program, overseen by the World Health Organization (WHO), eliminated the disease from most developed countries. But worldwide eradication proved to be much more complex than its proponents had hoped. Strains of Anopheles and Aedes mosquitoes resistant to insecticides and of Plasmodium parasites resistant to drug treatment presented scientific challenges and increased the costs of eradication. Political instability in many parts of the developing world, and a lack of funding from donor countries, discouraged further eradication efforts for decades.

Today malaria remains a major public-health threat in sub-Saharan Africa, where 80 percent of the world’s known cases occur. In 2009, WHO reported 225 million cases of malaria and 781,000 deaths. While this was a decline from the 985,000 deaths in 2000, in sub-Saharan Africa malaria remains one of the leading causes of death among people of all ages, and the leading cause of death among children, with one in every five deaths resulting from the disease. Although there are effective methods for controlling rates of infection and medications that can treat malaria, poverty and inadequate health-care systems on national and local levels limit their use.

Potential value of a malaria vaccine

Vaccines are a time-tested and indispensable public-health tool. Other methods of combating malaria—such as indoor spraying (with pesticides that also act as effective repellents, like dichlorodiphenyltrichloroethane, or DDT), the use of insecticide-impregnated bed nets, and the treatment of malaria with drugs—while not particularly expensive, all require a large infrastructure for delivery. Vaccines are viewed as a “cheap, simple technology” that is especially valuable in countries with underfunded health systems.

Furthermore, the development of pesticide-resistant mosquitoes and drug-resistant strains of malaria is a growing concern for public-health officials. Vaccination may be a valuable tool in confronting this problem, because it can reduce the need for drug therapy.

Diseases of the poor tend to receive inadequate funding. Even despite the potential value of a malaria vaccine, there had been little investment in developing one until recently. Developing an effective malaria vaccine is particularly complicated because malaria-causing protozoa are genetically more complex than a virus or bacterium, and any vaccine would have to be effective against several strains of the deadliest malaria parasites.

Vaccines are important, but they are not magic solutions that allow us to ignore the need for improved, more effective health systems.

Despite these challenges, the Bill & Melinda Gates Foundation, in particular, has helped to reinvigorate the fight against malaria. In 1999 the Foundation made its first $50 million grant for the development of a malaria vaccine. In 2007 Melinda Gates announced the Foundation’s goal of eradicating malaria. The Gates Foundation has provided funds for a multipronged attack on the disease: more than $150 million to support basic vaccine research and clinical trials, another $100 million to develop new drug treatments, and about $50 million to develop new insecticides. These actions of the Gates Foundation have been catalytic, helping to generate record private and public spending on vaccine development. Some believe a malaria vaccine may be available by 2015, but others are more wary.

The danger of shifting priorities

This renewed focus on a disease as debilitating as malaria is overdue. Nevertheless, critics worry that vaccines could be viewed as a substitute for low-tech preventive interventions like clearing swamps, distributing insecticide-treated bed nets, and indoor spraying. Few argue that these are mutually exclusive options, and the Gates Foundation has invested in the development of all of these technologies. But the massive amount of money required to develop a vaccine, coupled with the apparent simplicity of the approach, could reduce the availability of resources for other interventions. “The danger of the Gates call for a new era of elimination is that their immense funding power and influence…could cause damaging swings in funding and political priorities.…funding for malaria control is falling well behind what it needs to be,” wrote Pam Das and Richard Horton in a November 2010 Lancet editorial.

The notion that vaccines can be substitutes for effective public-health and health-care delivery systems is a myth. Vaccines may require fewer medical professionals and a less well developed public-health system than other interventions, but that does not suggest that they can be administered without such a system. Vaccines are complements to, not substitutes for, an organized health system. In the United States, children living in poverty and/or without a regular source of care are less likely to receive up-to-date vaccinations. Without an appropriate health system, the existence of a vaccine is of limited value.

Effective, broad-based health-care systems are important, not only to combat malaria, but to address the broad array of threats to health in Africa and the rest of the developing world. Reducing the prevalence of malaria may be necessary to improve health in Africa, but it is not sufficient. Africa is just beginning to experience the so-called “double burden” of disease experienced by people living in other parts of the developing world. Alongside parasitic and other infectious disease, rates of noncommunicable disease are projected to rise during the next several years. Deaths due to cancer, for example, will increase dramatically during the next decade. Without adequate health systems, cancer patients in Africa will not have access to screening, early diagnosis, adequate treatment, or palliative care.

Vaccines are important, but they are not magic solutions that allow us to ignore the need for better health-care systems. Enthusiasm for the development of a vaccine is appropriate, but must not crowd out investments in health-system infrastructure or the continued funding of more familiar, but still effective prevention and treatment efforts.

Michael K. Gusmano is a research scholar at The Hastings Center, an independent bioethics research institute in Garrison, NY. He is the author (with Colleen Grogan) of Healthy Voices/Unhealthy Silence: Advocating for Poor People’s Health, and a coauthor of Health Care in World Cities: New York, Paris, and London, published last year by The Johns Hopkins University Press.

 

 

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Comments

Avatar of: napoleon

napoleon

Posts: 1457

June 20, 2011

Thank you for your excellent article. Many among the Gates foundation keep pumping money in excess to eradicate children diseases. Excellent and high kudos for them. But as a biomedical researcher I question myself "if it is the right direction to solve problems.  It is terrible seen these children suffering because some simply vaccine will help them to survive. However,my question is if the Gates foundation is pouring billions of dollars in saving these children, do they plan to invest in giving them education or jobs when they are saved and well. Would not be better to educate people more about contraception and birth control, therefore the less children the better life their parents can afford and maybe you will no save a lot of children that they will face a difficult future with life, education nutrition etc.  I think it should be a question to ask the Gates foundation in  a serious manner. Is Microsoft going to offer jobs and education to all those children that the vaccines are saving .

Avatar of: ggg

Anonymous

June 20, 2011

I don't think Microsoft as a company is a charity organization. 

Avatar of:

Posts: 0

June 20, 2011

Thank you for your excellent article. Many among the Gates foundation keep pumping money in excess to eradicate children diseases. Excellent and high kudos for them. But as a biomedical researcher I question myself "if it is the right direction to solve problems.  It is terrible seen these children suffering because some simply vaccine will help them to survive. However,my question is if the Gates foundation is pouring billions of dollars in saving these children, do they plan to invest in giving them education or jobs when they are saved and well. Would not be better to educate people more about contraception and birth control, therefore the less children the better life their parents can afford and maybe you will no save a lot of children that they will face a difficult future with life, education nutrition etc.  I think it should be a question to ask the Gates foundation in  a serious manner. Is Microsoft going to offer jobs and education to all those children that the vaccines are saving .

Avatar of:

Posts: 0

June 20, 2011

I don't think Microsoft as a company is a charity organization. 

Avatar of:

Posts: 0

June 20, 2011

Thank you for your excellent article. Many among the Gates foundation keep pumping money in excess to eradicate children diseases. Excellent and high kudos for them. But as a biomedical researcher I question myself "if it is the right direction to solve problems.  It is terrible seen these children suffering because some simply vaccine will help them to survive. However,my question is if the Gates foundation is pouring billions of dollars in saving these children, do they plan to invest in giving them education or jobs when they are saved and well. Would not be better to educate people more about contraception and birth control, therefore the less children the better life their parents can afford and maybe you will no save a lot of children that they will face a difficult future with life, education nutrition etc.  I think it should be a question to ask the Gates foundation in  a serious manner. Is Microsoft going to offer jobs and education to all those children that the vaccines are saving .

Avatar of:

Posts: 0

June 20, 2011

I don't think Microsoft as a company is a charity organization. 

Avatar of:

Posts: 0

June 21, 2011

I did an unpublished lit search at measles vaccine efficacy in Africa, the first world and eastern bloc. In general, African VE for those who were vaccinated was was on the order of 65% to 85% when administered**. Since coverage was similar, overall VE was 50% or less. The former is probably due to lack of cold chain and overly long periods spent on the bench prior to injection. Additionally, in Africa, no published VE study mentioned anything but single dose vaccination. 

**It should be noted that many of those vaccinated subjects with insufficient antibody titers may have priming immunity established, and will still be protected, having light or subclinical infections. Those subjects without sterilizing antibody immunity will be expected to be communicators of the disease, and may well be superspreaders, which complicates evaluation of effectiveness of vaccination. (This latter is an open question.)

VE for vaccinated subjects in the first world are 88% to 98% with coverage in the 91% to 98% range. In these studies, 2 dose subjects amounted to 70% to 95%.

In animal work, the availability of a heat stable rinderpest vaccine was critical to that success in Africa. Similarly, in humans, if you seriously want to achieve success then you have to start from the beginning with a heat-stable vehicle. Those heat stable vaccines will probably not be appropriate for use in the developed world, and we should understand that from the get-go. There will be trade-offs between effectiveness overall and side-effects, including rare reactions/infections potentially from the vaccine. The worlds are far apart in this way and we need to be cognizant of that.

There are only approaches that I know of to develop a heat stable vaccine.
A. DNA vaccination. This has good protective characteristics generating cellular immunity, but low antibody titers.
B. Vaccinia based vaccine. This virus is extremely hardy and deals very well with additional antigens engineered into it. There may be other viral vectors but few are as good.

Avatar of:

Posts: 0

June 21, 2011

Author does not mention that antimalarial vaccine development started more than 30 years ago gulping ~50 % of all research budgets. None of the tested vaccines gave more than 65 % protection which lasted less than a year (requiring frequent re-vaccination). 
Combination of bed nets, indoor DDT spraying and intermittent prophylactic treatments are able to reduce the malaria burden by 60-80 % (depending on coverage). Obviously, the same efficient health care system is needed both for vaccination and for the combined prevailing, successfully tested means, but vaccine development is MUCH more expensive! Hence, the problem of priorities raised by tyhe author is very real.
N.B. Eradication of malaria in developed countries was achieved earlier than the WHO campaign the 50-60's. In fact, the WHO campaign in South-East Asia and in Africa led to the development of parasite resistance to chloroquine, until then the cheapest and most efficient drug. 

Avatar of:

Posts: 0

June 21, 2011

This is a worthwhile point, but how much this matters also depends on the disease. For instance, HIV tends to have a much more severe effect because it strikes down adults in their prime. This results in millions of orphans. Orphan boys in particular are excellent cannon fodder for warlords. They contribute massively to crime as well.

I would suggest that you take a look at Hans Rosling's GapMinder site. It has a great deal of very well presented statistical information along the lines you are discussing. http://www.gapminder.org/

Avatar of:

Posts: 0

June 21, 2011

I think we should look much closer to home these days. Our anti-tax crusading is putting us into a situation where we don't have jobs for our own. It is one of the roles of government to create the projects that in turn generate the jobs by investing in positive ROI projects. (Also, the USA is, today, the lowest tax to GDP of any developed nation. Look it up. Was in 2009, and that continues.)

Avatar of:

Posts: 0

June 21, 2011

I did an unpublished lit search at measles vaccine efficacy in Africa, the first world and eastern bloc. In general, African VE for those who were vaccinated was was on the order of 65% to 85% when administered**. Since coverage was similar, overall VE was 50% or less. The former is probably due to lack of cold chain and overly long periods spent on the bench prior to injection. Additionally, in Africa, no published VE study mentioned anything but single dose vaccination. 

**It should be noted that many of those vaccinated subjects with insufficient antibody titers may have priming immunity established, and will still be protected, having light or subclinical infections. Those subjects without sterilizing antibody immunity will be expected to be communicators of the disease, and may well be superspreaders, which complicates evaluation of effectiveness of vaccination. (This latter is an open question.)

VE for vaccinated subjects in the first world are 88% to 98% with coverage in the 91% to 98% range. In these studies, 2 dose subjects amounted to 70% to 95%.

In animal work, the availability of a heat stable rinderpest vaccine was critical to that success in Africa. Similarly, in humans, if you seriously want to achieve success then you have to start from the beginning with a heat-stable vehicle. Those heat stable vaccines will probably not be appropriate for use in the developed world, and we should understand that from the get-go. There will be trade-offs between effectiveness overall and side-effects, including rare reactions/infections potentially from the vaccine. The worlds are far apart in this way and we need to be cognizant of that.

There are only approaches that I know of to develop a heat stable vaccine.
A. DNA vaccination. This has good protective characteristics generating cellular immunity, but low antibody titers.
B. Vaccinia based vaccine. This virus is extremely hardy and deals very well with additional antigens engineered into it. There may be other viral vectors but few are as good.

Avatar of:

Posts: 0

June 21, 2011

Author does not mention that antimalarial vaccine development started more than 30 years ago gulping ~50 % of all research budgets. None of the tested vaccines gave more than 65 % protection which lasted less than a year (requiring frequent re-vaccination). 
Combination of bed nets, indoor DDT spraying and intermittent prophylactic treatments are able to reduce the malaria burden by 60-80 % (depending on coverage). Obviously, the same efficient health care system is needed both for vaccination and for the combined prevailing, successfully tested means, but vaccine development is MUCH more expensive! Hence, the problem of priorities raised by tyhe author is very real.
N.B. Eradication of malaria in developed countries was achieved earlier than the WHO campaign the 50-60's. In fact, the WHO campaign in South-East Asia and in Africa led to the development of parasite resistance to chloroquine, until then the cheapest and most efficient drug. 

Avatar of:

Posts: 0

June 21, 2011

This is a worthwhile point, but how much this matters also depends on the disease. For instance, HIV tends to have a much more severe effect because it strikes down adults in their prime. This results in millions of orphans. Orphan boys in particular are excellent cannon fodder for warlords. They contribute massively to crime as well.

I would suggest that you take a look at Hans Rosling's GapMinder site. It has a great deal of very well presented statistical information along the lines you are discussing. http://www.gapminder.org/

Avatar of:

Posts: 0

June 21, 2011

I think we should look much closer to home these days. Our anti-tax crusading is putting us into a situation where we don't have jobs for our own. It is one of the roles of government to create the projects that in turn generate the jobs by investing in positive ROI projects. (Also, the USA is, today, the lowest tax to GDP of any developed nation. Look it up. Was in 2009, and that continues.)

Avatar of: Brian Hanley

Brian Hanley

Posts: 66

June 21, 2011

I did an unpublished lit search at measles vaccine efficacy in Africa, the first world and eastern bloc. In general, African VE for those who were vaccinated was was on the order of 65% to 85% when administered**. Since coverage was similar, overall VE was 50% or less. The former is probably due to lack of cold chain and overly long periods spent on the bench prior to injection. Additionally, in Africa, no published VE study mentioned anything but single dose vaccination. 

**It should be noted that many of those vaccinated subjects with insufficient antibody titers may have priming immunity established, and will still be protected, having light or subclinical infections. Those subjects without sterilizing antibody immunity will be expected to be communicators of the disease, and may well be superspreaders, which complicates evaluation of effectiveness of vaccination. (This latter is an open question.)

VE for vaccinated subjects in the first world are 88% to 98% with coverage in the 91% to 98% range. In these studies, 2 dose subjects amounted to 70% to 95%.

In animal work, the availability of a heat stable rinderpest vaccine was critical to that success in Africa. Similarly, in humans, if you seriously want to achieve success then you have to start from the beginning with a heat-stable vehicle. Those heat stable vaccines will probably not be appropriate for use in the developed world, and we should understand that from the get-go. There will be trade-offs between effectiveness overall and side-effects, including rare reactions/infections potentially from the vaccine. The worlds are far apart in this way and we need to be cognizant of that.

There are only approaches that I know of to develop a heat stable vaccine.
A. DNA vaccination. This has good protective characteristics generating cellular immunity, but low antibody titers.
B. Vaccinia based vaccine. This virus is extremely hardy and deals very well with additional antigens engineered into it. There may be other viral vectors but few are as good.

Avatar of: David Stern

Anonymous

June 21, 2011

Author does not mention that antimalarial vaccine development started more than 30 years ago gulping ~50 % of all research budgets. None of the tested vaccines gave more than 65 % protection which lasted less than a year (requiring frequent re-vaccination). 
Combination of bed nets, indoor DDT spraying and intermittent prophylactic treatments are able to reduce the malaria burden by 60-80 % (depending on coverage). Obviously, the same efficient health care system is needed both for vaccination and for the combined prevailing, successfully tested means, but vaccine development is MUCH more expensive! Hence, the problem of priorities raised by tyhe author is very real.
N.B. Eradication of malaria in developed countries was achieved earlier than the WHO campaign the 50-60's. In fact, the WHO campaign in South-East Asia and in Africa led to the development of parasite resistance to chloroquine, until then the cheapest and most efficient drug. 

Avatar of: Brian Hanley

Brian Hanley

Posts: 66

June 21, 2011

This is a worthwhile point, but how much this matters also depends on the disease. For instance, HIV tends to have a much more severe effect because it strikes down adults in their prime. This results in millions of orphans. Orphan boys in particular are excellent cannon fodder for warlords. They contribute massively to crime as well.

I would suggest that you take a look at Hans Rosling's GapMinder site. It has a great deal of very well presented statistical information along the lines you are discussing. http://www.gapminder.org/

Avatar of: Brian Hanley

Brian Hanley

Posts: 66

June 21, 2011

I think we should look much closer to home these days. Our anti-tax crusading is putting us into a situation where we don't have jobs for our own. It is one of the roles of government to create the projects that in turn generate the jobs by investing in positive ROI projects. (Also, the USA is, today, the lowest tax to GDP of any developed nation. Look it up. Was in 2009, and that continues.)

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