Vaccines in the Developing World

November 11, 2011
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 When we think of vaccines we need to divide the world into the industrialized countries, those with transitional economies and the developing countries. In the developing world, the proportion of the population less than 15 is very high, e.g., Mali has about 50% of its population under age fifteen compared to about 15% in the industrialized countries. This suggests that the emphasis in the developing world should be on preventing infection in the young. In the developing countries the top four causes of mortality in children less than five years old are pneumonia, diarrhea, malaria and measles (Myron Levine, MD, Director Center for Vaccine Development, University of Maryland Medical School).

 Pneumonia is mostly caused by the Streptococcus pneumoniae, Hemophilus, and respiratory syncythial virus (RSV,) all infections for which vaccines exist and are in general use in the industrialized world. Diarrhea is frequently caused by rotavirus, shigella and enterotoxogenic E.coli called Vaccines exist for many of these as well.

 There is no vaccine for malaria but there has been substantial progress. World wide there are about 500,000 million people of all ages infected and 1-3 million die each year so this is a clear priority.

 As for measles, there is an excellent vaccine which has essentially eliminated this infection from the industrialized world; but not in the developing world. The story is sort of like polio.  Humans are the only host so it can be eradicated if everyone is immunized. The measles vaccine is very effective. Mass immunization stops its spread. But in the developing world it is still common because vaccination is not widely enough utilized.

 In the developing world some other key needs are immunization for the other basics such as diphtheria, pertussis, tetanus, and Hemophilus type b infections. These all remain scourges of many developing countries with high morbidity and mortality. Even polio has yet to be totally eradicated.

 Many of these have long since been effectively eliminated from causing disease in developed countries, although gaps in coverage lead to problems on a regular basis. The economic benefit not to say the toll in human suffering would be enormous if these were controlled in the developing world. The Global Alliance for Vaccines and Immunization (GAVI) is a consortium agency that seeks funding from foundations (the Bill and Melinda Gates Foundation is their largest contributor) and governments while concurrently negotiating the best possible prices from the manufacturers and distributors. GAVI recently obtained over $20 million in funding and deep concessions from the pharmaceutical industry for vaccinations in the coming year.

 Polio was close to eradication in the mid 1990s and indeed the last case of serotype 2 was found in 1999. But then the worldwide effort subsided sufficiently that progress toward eradication of the other two serotypes faltered. A new bivalent vaccine became available in 2009 and its use plus new tactics to reach missed children were initiated. Now cases are down by 95% with the largest reservoirs in northern India and in Nigeria along with transmitted cases in Pakistan and Afghanistan along with several African countries near Nigeria. With continued efforts it is quite possible that polio can be eradicated although the issue of vaccine-derived poliovirus may persist for some time.

 Meningitis caused by Group A Neisseria meningitidis causes epidemics, mostly among those aged 1 to 29, every decade or so across a wide swath of Africa from Senegal to Ethiopia. There is a licensed vaccine but it does not create long lasting immunity. A new conjugate vaccine (PsA-TT) which will cost only about 50 cents per dose and funded by the Gates Foundation has been recently evaluated (N Engl J Med June 16, 2011).  Compared to the older vaccine and another control, the new vaccine produced high antibody responses and a long lasting anamnestic response with comparable minor side effects.

 Rotavirus, discussed in a different post, is also an important problem in developing countries. The original vaccine licensed in 1998 proved to have a small but definite risk of intussusception in the ensuing 10 days. This led to the development of two new vaccines (Merck and Glaxo) which when tested in large populations did not seem to cause intussusception. In the United States about 60% of infants and children are now vaccinated with about 85% reduction in hospitalizations and ER visits. Given that in the past some 400,000 children would be infected with diarrhea and 55-70,000 were hospitalized, this is a remarkable test of efficacy and value. They are now used world wide and the rates of hospitalization in developing countries have come down sharply suggesting very good efficacy. Now that the vaccines have been available for some time, follow-up studies on much larger populations have been done (N Engl J Med June 16, 2011). In evaluations in Mexico intussusception was found to occur in about 1 in 51,000 children during the 7 days post first vaccination. This corresponds with the peak replication of the virus in the GI tract. In Brazil, the rate was 1 in 68,000 but mostly in the week after the second dose. A possible reason for the differences is that in Brazil the first dose of rotavirus vaccine is given with the oral polio vaccine; the latter suppresses the replication of rotavirus. Bottom line – the risk benefit equation clearly favors vaccination.

 AIDS is not just a problem for the developing world but for industrialized societies as well. However I will place these comments here.

 AIDS was first recognized in a report from the Centers for Disease Control (CDC) in June 1981. Just 30 years later, with about 2,700,000 new infections per year worldwide, a vaccine cannot come soon enough. 

 Only a vaccine will ultimately drive the epidemic down and possibly even contain or eradicate it the way smallpox was or polio and measles could be. HIV has proven to be very difficult to conquer with a vaccine. Some of the problems include that the initial infection usually goes unnoticed and then it remains latent for many years until the earliest evidence of AIDS appears. Another is the ubiquity of the virus and its ability to undergo sufficient change to escape immune detection. Once the T cell is infected, it is infected for life so a vaccine must be used before, not after, exposure. Of course, there has never been a vaccine produced before to a retrovirus so this in itself is a new hurdle with limited knowledge from former vaccine research to base today’s work upon.

The vaccine must block the virus’ ability to enter the cell suggesting an antibody rather than a cellular immune-based vaccine. Dr Robert Gallo, co-discover of HIV/AIDS virus – (director of the Institute of Human Virology) believes the target must be the virus envelope – the “fingers” that attach to the T lymphocyte. He and his colleagues recently received over $24 million from the Gates Foundation and the military to further research in this direction. Many others have HIV vaccine studies in progress.

HIV/AIDS has been a vexing epidemic and development of a vaccine has been just as vexing. But progress is being made and perhaps there will be one available within the decade. Meanwhile, vaccines that are already available for infectious diseases that kill millions of individuals, mostly children, in the developing world are available – the need is to get them distributed. The economic implications not to mention the improvement in the human condition would be enormous.

Vaccine use in the developing world will have the greatest opportunity to prevent infection, reduce morbidity and mortality dramatically and ultimately have a major positive economic impact for these peoples and countries. It is a medical megatrend to be hoped for.

 

Stephen C Schimpff, MD is an internist, professor of medicine and public policy, former CEO of the University of Maryland Medical Center and consults for the US Army, medical startups and Fortune 500 companies. He is the author of The Future of Medicine – Megatrends in Healthcare. Updates are available at http://medicalmegatrends.blogspot.com

 

 

 

 

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