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December 31, 2010
2011 Global Health Resolutions
Today is the last day to make New Year’s Resolutions (on the western calendar, anyway), and so I thought I’d make a list of what I think the humans on Planet Earth should try to accomplish in global health this year. I welcome your inputs on this as well. Just add them in the comments section below.
1. “Eliminate” polio.
This one has been on everyone’s list for many years now, but we are closer than ever. This is, of course, subject to the realization that most diseases for which there are vaccines are rarely completely eliminated, but let’s get as close as we can.
2. Cut meningitis infection in Africa by 75%.
I think with the new vaccine approved by the WHO recently and now available in Niger, Burkina Faso, and Mali, we are closer than ever to removing this scourge from the lives of children the world over.
3. Continue advances in diagnosing and treating TB using DOTS.
DOTS is a remarkable success story in many countries, but not in all. We need to find ways to make TB treatment more uniform and successful across the world. Recently-approved rapid diagnostics for TB will help.
4. Drive advances in helminth diagnosis and research.
Helminths are a bane on the human population and have been for centuries, if not always. There is relatively little work in this area, yet the effects of helminth infection, particularly in children, are huge. More work clearly needs to be done. I personally resolve to look at the feasibility of molecular diagnostics for helminth infection using some of the work we are doing in malaria diagnosis in our lab.
5. Continue work in malaria diagnosis and treatment.
Here, there is also progress we can build on. A new vaccine is almost available, although it has critically low effectiveness. There are also new diagnostics being developed that may eliminate the cold-chain required to store and transport current tests.
6. Continue work in treating and preventing HIV/AIDS.
As the major killer world-wide, we need as much effort here to continue as possible. The knock-on effects of treating HIV/AIDS are definitely worth the effort.
December 27, 2010
Twice as fast
A major challenge facing global health is the disparity between the time it takes to develop a new therapeutic and the time until that therapeutic becomes obsolete due to drug resistance. Drug resistance is emerging against virtually every current therapeutic drug against global health diseases. Malaria is a classic example, where the use of symptomatic diagnosis, incomplete courses of treatment, and counterfeit drugs led to resistance against quinine, although that drug is still sold in some malaria-endemic regions. Malaria has also become resistant to chloroquine, sulfadoxine-pyrimethamine, mefloquine, and it is only a matter of time before resistance to the artemisinin family emerges (see Table). Many other diseases are also resistant, however, particularly the bacterial infections due to the fast lifecycles of bacteria and the ease with which they transfer genes horizontally. Ironically, the more antibiotic is available, the faster the emergence of resistance due to the effects mentioned above.
Resistance to malaria drugs. Source: P.B. Bloland, "Drug resistance in malaria", WHO, 2001.
A chart of the number of new antibiotics on the market per decade shows a steep decline in the past 20 years, to almost none today. This phenomenon is likely to be due to a number of causes, including market share, difficulty of discovering new antibiotic modes of action that evade resistance, and the lucrative potential of drugs for other first-world diseases including cancer. This notwithstanding, the trend is towards fewer new antibiotics and faster emergence of resistance.
Number of new antibiotics entering market by decade, 1940-2000. Data from: http://en.wikipedia.org/wiki/Timeline_of_antibiotics
The story is even more urgent when we consider vaccines. Vaccines are held as the silver bullet of global health because they are the only treatment method that provides long-term protection, significant knock-on effects within populations due to immunized individuals (known as herd immunity), and wide availability at low cost once the vaccine is developed. However, the timeline for development of new vaccines is long and arduous. Even here there is resistance, including the H1N1 strain of influenza, whooping cough, and meningitis C.
Exact numbers on how long it takes to develop a vaccine are hard to find, as this depends on the disease target, but a general estimate is between 9 and 14 years. The cost also varies, but can reach well into the hundreds of millions of dollars ($300-800 million). In contrast, H1N1 resistance to Tamiflu emerged in just under 5 years. As you can see, the timelines don’t match up – we are fighting a losing battle.
The solution is twofold. First, application of emerging technologies and methods to disease target discovery and potential vaccine candidates will speed the time it takes to develop a candidate vaccine that can enter clinical trials. After this point is where the policy and the economics enter. Although the research is expensive, the clinical trials are extremely expensive. There needs to be a better way for drug companies to make the money they need to develop these vaccines, which will undoubtedly save millions of lives. The answer is upon us, I think. Within the last 10 years, several large pharmaceutical companies have spun off nonprofit vaccine development organizations focused on vaccines for neglected diseases. The nonprofit model fits these challenges well because there is virtually no way to make money on these vaccines and drugs. Once they are developed, they will be distributed at very low cost to the world’s critically poor, making sales an nonviable method to recoup costs. These nonprofits can apply for grants, raise donations, and use other methods to fund the critical research that needs to be done in order to ensure that the vaccines are developed, and that they are safe and effective.
Here’s the happiest news of all – you can help make this happen! Power to the people! You can donate or help raise funds for groups like the Sabin Vaccine Institute, the Novartis Vaccines Institute for Global Health, and PATH that are doing this critically important work. I have included links to many of them on the “Get Involved” page. I encourage you to donate so that others may live.
December 25, 2010
Season’s Greetings!
Happy Holidays and best wishes for a new and globally healthy year to everyone! I will return in early January with further posts.
Eric
December 11, 2010
The challenges of detecting diseases that are constantly evolving
It has been an interesting couple of weeks around here. First of all, we hear of the mystery disease afflicting Uganda, from which at last count 35 people have died. Closer to home, we heard a seminar by Dr. Jesse Bloom, who is doing amazing work predicting influenza’s future resistance to Tamiflu. Finally, we hear about the WHO promulgating a new 2-hour TB detection test, saying it should be rolled out worldwide. What do all of these items have in common? Two things. First, the need for diagnostics is ever-present. Even when treatments and vaccines are available, there will be a need for diagnostics. Second, these diagnostics need to be adaptable, because sure as birds fly, the causative agents will eventually mutate and skirt around both the diagnostics and the treatments that are currently available.
The challenge of how to make diagnostics sensitive, specific, but also adaptable is a tough problem. Usually, to make diagnostics specific and sensitive you have to target a part (usually molecular) of the causative agent that is very well known and characterized. This takes time, effort, and assumes that this molecule isn’t changing on the time scale that you characterize it. For this reason, most diagnostics and treatments typically target highly conserved parts of the organism, like critical metabolic enzymes, transporters, or signaling molecules. However, these can and do change. The Tamiflu example is evidence of this. Tamiflu (actually known as oseltamivir) targets the influenza nueraminidase enzyme, which is used by the virus to enter host cells. However, the authors of this work showed that it was not even the main known mutation of this enzyme that is allowing the virus to evade oseltamivir, but secondary mutations in the gene sequence that are acquired over time as the virus propagates throughout the world. These secondary mutations in combination with the main mutation (a single amino acid change, by the way) allow the virus to evade the drug. Not good.
The other examples of diagnostics above are equally challenging. TB is caused by Mycobacterium tuberculosis, a bacterium that, like all other bacteria, evolves on a very rapid timescale. Luckily, TB evolves more slowly because it grows more slowly than other bacteria, making the time between generations longer. The final example, this mystery disease in Uganda, is suspected to be a new variant of amoebic dysentery. In this case, there is no molecular diagnostic even available, and the most common diagnostic method, microscopy, requires multiple samples due to the rapidly changing number of amoeba in the stool.
So, what is the solution? I suggest high-throughput DNA sequencing. Our new ability to sequence organisms from complex samples at a fraction of he time and cost of previous methods makes it simple to detect the mutations that may cause immune, diagnostic, or therapeutic evasion. H1N1 was a good example of this (see the previous post on this). If we know what the mutations are, we can apply emerging computational, directed evolution, and molecular modeling tools to design new diagnostics and drugs. The final step of this, though, is the time and effort required to validate these new diagnostics and drugs and get them cleared for public use. Stay tuned for my next post about this issue.
