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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.
November 28, 2010
New UN Human Development Report a winner
I find the recent 2010 UN Human Development Report fascinating. One of the major criticisms of the Human Development Index over the years has been that it is a composite index that averages across countries, essentially ignoring the sometimes huge disparities within countries. Many have argued that these should be accounted for in the rankings. I could not agree more, and am happy to see that the UN has indeed done this in this 20th anniversary edition of the HDR and its Development Index rankings. The new Inequality-adjusted Human Development Index takes into account disparities in health, education, and income, and the results are quite striking. As well as giving a glimpse into the error bars on the HDI within countries, it allows for a more nuanced view of multidimensional poverty. I grabbed a smattering of my favorite countries off the list and compared their 2009 HDI ranks, their 2010 HDI ranks, and their new inequality-adjusted (IDHI) ranks. As you can see, the US needs improvement, and look at Peru!
In all cases, the IHDI rank is lower than the non-adjusted HDI rank. I also grabbed and plotted the new Gender Inequality Index for each of these countries. Those results are also striking. Here, the larger the index, the worse the country is at gender equality.
Some other graphics in the report are interesting as well. See, for example, the disparities present within the different provinces of Kenya (Figure 5.11), the losses due to gender inequality by region (Figure 5.4), and a dot plot presenting the lack of correlations between the HDI and the broader dimensions of human development (Figure 4.1).
All in all, the 2010 HDR is a winner – I recommend you download a copy and read through it. I think everyone can learn a lot from it.
October 27, 2010
Technology for diagnosing and treating mental illness
Mental illness is the giant elephant in the middle of the global health room. According to the WHO, depression will soon be the leading cause of disability worldwide – 3,000 people commit suicide every day (125/hour, 2/minute). And, of those that complete suicide, there are 20 more who attempt it but don’t complete it. A recent PLoS Medicine paper indicates that a third of suicides in developing countries are committed using agricultural pesticides. Finally, after recent gay-bashing incidents led to well-publicized suicides in the US, the Obama administration made a personal appeal to those who are being bullied to stay alive and to seek help. Given this tremendous toll, and the paucity of funding (at least in developed countries) for mental health issues, is there a role for technology to help?
One of the first interventions that springs to mind is mHealth. The use of cellular phones to connect people in remote locations with professional help seems like a critical facet of intervention. Beyond simply using the phone as a phone, are there possible diagnostics or screening that one might do with cell phones? Various attempts have been made (iPhone apps) but I find a lack of such programs in the development context. Even the UN Foundation/Vodafone mHealth report released recently does not use the word “mental” beyond a cursory mention of smoking cessation programs. There have been studies on the use of automated depression screening for pregnant women by cell phone, and certainly examples exist of computerized screening through cell phones or land-line phones. Where mHealth (as well as any other screening tool) may be limited is its ability to embed the results of screening into a health care system that can act on the information.
Even in developed countries, just because a test result indicates you might be depressed, there is no guarantee that a) you will get help for the condition or that b) the depression will be cured. The challenges of mental health intervention are therefore similar in some ways to, say, infectious disease, in that significant difficulty exists on the treatment end as well as the diagnosis end. However, where mental illness is different is in its multiplicative effects and on the costs associated with treatment. If a mental illness exists, it may make treatment of other ailments (like infectious diseases) more difficult. If the mental illness can be treated, it usually requires years and can require repeated hospitalizations (depending on the condition). The frightening part of some mental illnesses is the growing body of medical evidence that indicates that such conditions are immutable once initiated.
The good news, however, is that perhaps they can be prevented. There is ample evidence that markers of poverty and markers of mental illness are correlated, and so by addressing the issues of one, you can address the other as well. Therefore technologies useful in other areas of poverty reduction, including water purification, vaccines, and inexpensive diagnostics for infectious disease, can reduce mental illness. So, there is a compound benefit to addressing poverty using a multi-pronged approach, a conclusion that should surprise nobody but the effects of which will be profound.
October 18, 2010
Maple syrup?
I was not surprised to hear of Canada’s failure to secure a seat on the UN Security Council last week, but I was surprised to hear that they lost the vote to Portugal. Poor, bankrupt Portugal. I think the act that sealed the deal, though, was the attempt by the Canadian delegates to “sweeten the deal” by giving certain member countries a gift of maple syrup in a last-ditch attempt to sway their votes. Maple syrup? For a seat on the UN Security Council? If the member countries weren’t already convinced that Canada didn’t care about the UN, this was a clarion call to that effect. Canada has been absent from all-important decisions of late on the world stage, and this is but one more indication that her Majesty’s colony is slipping from its moral high ground. The G20 convention was a madhouse and way too expensive, we have shifted development funding from Africa to Latin America, and our stance on the finer points of MDG5 at the G8 was embarrassing. I guess at least we are still signatories on the Land Mine treaty . For now. Maybe we should give the US some maple syrup to convince them to sign it.
October 6, 2010
Microfluidics for global health, Ch 2
In the last post, I began talking about microfluidics and how recent efforts are focused on applying this technology to global health diagnostics. This post is the conclusion of that one.
Other advances in microfluidics for global health have come in the form of new technologies for simplifying the methods used to fabricate microfluidic systems. Some of these advances are in materials and some are in methods. In the area of materials, the so-called Shrinky-Dink® microfluidics can be used to print a microfluidic chip pattern using a conventional printer on a special thermoplastic sheet; reheating the thermoplastic material then causes it to revert to its original size, reducing the ink patterns on the sheet as it does so. The resulting mould can be used to make microfluidic chips in minutes with very few materials and common equipment. Another advance comes in the use of Jell-O®, the popular gelatin dessert, to make microfluidic chips. This is work from Tony Yang, a student in my lab, and although the feature sizes in the final devices are larger than the usual 0.1mm, the flow is still laminar. These chips were designed for educational use, but I wonder if the use of other locally available biopolymers might make these sorts of chips useful for global health diagnostics.
The final advance comes in the form of Dean flow, a topic I have discussed previously on this blog. Using the nonlinear equations of fluid flow, it becomes possible to design microchannel geometries that focus particles by size without applying any forces other than those used to drive the flow. A simple pump could therefore be used to remove bacterial pathogens or protozoans from drinking water, to purify certain types of cells, or many other uses. I look forward to seeing where this technology base will take us in the future.
September 26, 2010
What is a preventable death?
I saw Amnesty’s Maternal Death Clock the other day, and never one to be outdone in Javascript (yeah, right), I made my own counter. This one counts global heaths due to malaria, TB, pneumonia, diarrhea, and HIV/AIDS since the beginning of each year. Originally, I had intended to call this a “preventable” death counter, but it made me consider what the definition of “preventable” really is. In theory, lots of deaths are “preventable”, but the effort required to prevent many of them would severely curtail development in other areas of life. For example, are all car accident deaths preventable? Certainly, if we don’t allow anyone to drive. How about deaths due to type II diabetes? Certainly, if we restrict the types of food people are allowed to produce, sell, and consume. Now, how about deaths due to malaria? Most of these would be preventable, assuming the artemisinin works and we can get it to the people who need it. The ultimate would obviously be a vaccine, but even here you wouldn’t completely be guaranteed of preventing all deaths. So, are deaths due to malaria really preventable? How about HIV/AIDS? I would like to think they are, but perhaps this is overly idealistic. Looking at the huge numbers displayed on my counter, which are taken from the WHO’s factsheets on mortality from each of these diseases every year, it seems to me impossible that we will ever drive these numbers to zero, the implication of our true ability to prevent death. So, I guess the question remains, how close to zero can we get? Is 99% “preventable” a contradiction in terms? Would I be satisfied with this outcome? Would you?
