#104 A Doctor Returns to Somaliland

#104 A Doctor Returns to Somaliland:
After 20 years outside the country, Dr. Sohur Mire came back to Somaliland to work with Doctors Without Borders/Médecins Sans Frontières (MSF). Somaliland is a nominally autonomous region of northern Somalia.

Removing Barriers to Access for a More Equitable, Healthy World NOVEMBER 21, 2012

Removing Barriers to Access for a More Equitable, Healthy World  NOVEMBER 21, 2012

ALL credits to MSF- Doctors without borders.

There wont be a better way to start new year than orienting to the task ahead. My friends lease read it

MSF International President Dr. Unni Karunakara

MSF International President, Dr. Unni Karunakara, in his keynote speech at the 2012 Universities Allied for Essential Medicines conference:
Good evening and thank you very much for welcoming me here tonight. I’d particularly like to thank Rachel Kiddell-Monroe and Bryan Collinsworth for the invitation.
It’s incredibly inspiring to look out and see a room full of students who choose to spend their spare time advocating on behalf of millions of people who lack access to lifesaving medicines. So thank you all for being here today, and for choosing to engage with UAEM, an organization whose work Médecins Sans Frontières—MSF—admires and supports.


Our two organizations have an important history together. In 2001, university students and MSF combined forces to lead a pivotal and successful campaign to pressure Yale University to adhere to its own patent licensing policy in relation to an important AIDS drug—a policy designed to ensure that its research benefited society in general.


That victory was a watershed moment in the fight against the AIDS epidemic in developing countries. It ultimately led Yale and its licensee, Bristol-Myers Squibb, to permit price-busting generic production of the AIDS drug. This, in turn, led other multinational pharmaceutical firms to make similar groundbreaking concessions.
That campaign gave rise to UAEM, the vibrant organization that you are a part of today.

If at times it may be difficult to see a tangible connection between the kind of work you do on your university campuses and the medical needs of patients on the ground in developing countries, you need only remember the story of Yale and Bristol-Myers Squibb bending to student activist and civil society pressure. The story that triggered massive price reductions in AIDS drugs, helping to bring them to 8 million people today.
Tonight I hope to further illustrate how vitally important your work with UAEM is to our patients.

As a medical humanitarian organization, MSF aims to deliver the best medical care possible to people whose very survival is threatened by armed conflict, epidemics, neglect, exclusion from health care, natural catastrophes, and man-made disasters.
Today, more than 30,000 MSFers—including doctors, nurses, logisticians, and support staff—work to assist populations in distress in more than 60 countries across the world.

But our teams are often hindered in delivering optimal—or even adequate—medical care. MSFers in the field grapple every day with the fact that the drugs, diagnostics, and vaccines needed to treat our patients are unavailable, unsuitable, or unaffordable.
When treating sleeping sickness in the Republic of Congo, I saw firsthand the hardships our patients have to endure. Without treatment, sleeping sickness is 100 percent fatal. But even those patients lucky enough to receive care suffer enormously. Diagnosing the advanced stage of sleeping sickness requires a spinal tap or lumbar puncture. Imagine performing this procedure in field conditions.At the time, the only treatment option we had for the advanced stage of the disease was an arsenic-based drug, melarsoprol. Melarsoprol is so corrosive it is nicknamed “fire in the veins.” We had to struggle with the knowledge that the drug we were prescribing had a one in twenty chance of killing, instead of curing, our patient.

What was even more frustrating was that we knew a safer drug existed. It existed, but it wasn’t available. The manufacturer had discontinued production for lack of profits.Thankfully, we no longer use melarsoprol. But the best treatment currently available is still complicated to administer. Patients must endure 14 injections over seven days. We still have to perform lumbar punctures.We desperately need a diagnostic tool and treatment for sleeping sickness that is safe, effective, and easy to administer in remote areas, where there is no water on tap, no electricity, and trained medical staff are scarce.Each year, millions of people die, and millions more suffer needlessly from diseases that can or should be prevented and treated.

This is unacceptable.It is unacceptable that 90 percent of those afflicted with multi-drug resistant tuberculosis don’t have access to treatment, and the few that do must endure a highly toxic two-year treatment regimen that can cost almost nine thousand dollars.
It is unacceptable that 22 million of the world’s children fail to receive basic life-saving vaccinations every year.
It is unacceptable that almost 50 percent of people living with HIV cannot access the lifesaving antiretroviral treatment that they need.
I’ve no doubt you agree. It’s why you’re here today, it’s why UAEM has to exist, and it’s why MSF continues to devote significant resources to breaking down barriers to access, through treating patients, but also through research and advocacy.
Tonight, I want to talk about how changes in the global health landscape are affecting patients. I will discuss how access to health care can be—and has been—incrementally improved by implementing practical solutions. But it is not enough. We need a sea change in our approach to ensure that scientific advances are consistently translated into better care for patients.
It is the kind of change that can only be provoked by a strong grassroots movement that brings together frontline medical practitioners, patient groups, activists, researchers, and others with a common goal—ensuring access to lifesaving medicines. By sharing the experiences of our patients, I hope to show you what needs to happen on university campuses, in negotiating halls, in laboratories, and in conference rooms, if we are to make a long-term difference in the lives of our patients. Tonight is about the perspective from the ground, and how you can affect it.
Over the past two decades, a massive transformation has taken place in global health. Global health has claimed a bigger space on the international political agenda and received huge increases in financial resources.

Spending almost doubled from 1990 to 2000, from $6 billion to $11 billion. By 2011,it had leapt to $28 billion.
The past two decades have undeniably yielded incredible gains.
• A 41 percent reduction in child mortality from 1990 to 2011
• A 33 percent decline in malaria mortality rates in Africa over the past ten years
• Eight million HIV-positive people on ARV treatment
The strong focus on health indicators in the Millennium Development Goals certainly helped spur these achievements. In parallel, powerful new actors and radically different program approaches have emerged.

The World Health Organization, once the dominant global health actor that set technical norms and priorities for funding and research, now shares the stage with a host of other influential institutions. In the 1990s, the World Bank emerged as one of the largest global health funders. And the past decade has seen the Bill and Melinda Gates Foundation rise to become one of the largest donors in terms of expenditure, distributing $2 billion in global health grants last year.


Major global health initiatives, such as the Global Fund to Fight AIDS, Tuberculosis, and Malaria, GAVI—the Global Alliance for Vaccines and Immunization—and the US’s PEPFAR program, together pumped $8 billion into global health programming in 2011.
The so-called BRICS countries—the rising economic powers of Brazil, Russia, India, China, and South Africa—have increased the size and scope of their efforts in global health and development assistance. Their emergence is challenging the traditional North-South paradigm in no small way.
The mobilization of civil society actors means that organizations like MSF and UAEM have become even more relevant.
The gains we have seen, however, are fragile, and formidable tasks remain before us.We have fallen into a period of financial crisis, and of donor retreat.Moreover, the MDGs have almost run their course, and the Sustainable Development Goals that are likely to take the global agenda forward are putting the prioritization of health at risk.We need to ask fundamental questions about the approaches, governance and longer-term impact of the transformation in global health.

We must scrutinize the trend of governments turning to a mix of public and private actors, including multinational corporations, private foundations, and civil society to confront major health challenges. For example, the Gates Foundation’s influence on global health extends well beyond the development of new technological solutions. It seeks to direct program implementation, priority-setting, public health policymaking, and medical and scientific norm-setting.We must also look at how donor habits are changing. Donors are selecting the programs that they wish to fund, rather than funding core operating budgets decided by states. Earmarked voluntary contributions to the World Health Organization and the World Bank have spiked in recent years. These can be risky, because donor priorities change: major health initiatives funded through voluntary donations have been subject to dangerous fluctuations in funding flows.In this new system of governance, scientific research and development priorities and access strategies are donor-driven more than they are patient-driven. The voices of our patients, who have some of the greatest and most urgent needs of all, are not being heard.UAEM's new University Global Health Impact Report Card reveals that the top sixty US and Canadian research universities devote an average of just 3 percent of their total biomedical research funding to neglected diseases. These are ostensibly public interest institutions. Their research is funded primarily by government grants. They should be working in the fields of medicine that are being neglected by others. Three percent is a shockingly low number.
This neglect has a direct effect on hundreds of millions of people. Senzo is just one of them. Senzo is seven. He is one of our patients in southwestern Swaziland. He is HIV-positive and is being treated for multi-drug resistant tuberculosis, or MDR-TB, meaning that his infection is resistant to the two primary anti-TB drugs. MDR-TB treatment is therefore much harsher than regular TB treatment.
Every day, Senzo wakes up and walks to catch a bus to the clinic for his injection. He also takes 14 pills every day. Because there are no drugs specifically formulated for children, his caregivers have to adapt adult dosages by breaking up pills. Some of the drugs taste terrible, and some have unpleasant side effects, such as nausea, vomiting, and diarrhea. It will take two years of treatment, and cost thousands of dollars, before Senzo is cured.
But Senzo is one of the lucky ones. MDR-TB is on the increase, but treatment programs are scarce. New data from MSF projects show alarming numbers of MDR-TB cases around the world. These have come as a shock even to our doctors in the field.
In the north of the Central Asian country of Uzbekistan, 65 percent of TB patients treated by MSF in 2011 were diagnosed with MDR-TB. MSF data reveals that MDR-TB is not only developing due to incorrect treatment, but is also transmitting in its own right. In southern Africa and Southeast Asia, HIV and MDR-TB infections are combining to make a toxic brew of disease.
Worldwide, less than 5 percent of TB patients have access to proper diagnosis of drug resistance. But wherever we look for drug-resistance, we are finding it in alarming numbers. This suggests that the global scope of MDR-TB is far more vast than previously estimated. It is also estimated that only 10 percent of people with MDR-TB have access to treatment—and this figure is an average. It is far lower in low-resource settings, where prevalence is highest.
This is a global crisis, which is being exacerbated by diagnostic tools and medicines that are outdated and hugely expensive. The toxic two-year treatment regimen is dominated by drugs developed in the middle of the last century.My first assignment with MSF was to set up a TB program in Jijiga, eastern Ethiopia, in 1995. It’s difficult to accept that almost 20 years later, this curable disease remains one of the developing world’s biggest killers, taking 1.4 million liveseach year.

This persistent plague perfectly illustrates how today’s medical innovation system is failing our patients.
Today’s system incentivizes companies to develop drugs and other medical tools based on the return on investment that the product will offer. Medical R&D therefore depends on the size of the likely market and on pricing.The TB drug market is small, and there is little incentive for competition. TB patients tend to be poor, and cannot pay high prices. There are few manufacturers, so drug prices remain prohibitively expensive. With little prospect of making a profit in such a small market, few companies are rushing to develop new products and join the competition.As Senzo is only too aware, there is a lack of pediatric diagnostics and formulations.
There is some good news. A new rapid diagnostic tool has the potential to massively increase early detection of drug-resistant TB. But it is too expensive for resource-poor settings, exactly where the ability to detect TB within hours—as opposed to days or weeks—is most needed.We are on the cusp of having two new drugs to fight TB. But we fear that, just as happened with the development of the first ARV drugs for HIV, these new medicines will be reserved only for those who can afford them.The world cannot sit back and ignore the threat of MDR-TB.This is one of the most pressing medical humanitarian crises in the world today.We must push for more people to be tested, treated, and cured.We must change the system of medical innovation.Right now, the link between R&D and pricing means that patients are losing out. Because the best way to maximize returns in today’s system is to control the market. Patents and other exclusive rights enable companies to protect the market for their products. Patents give exclusive rights to sell a product at any price the market will bear for a defined period, usually 20 years.

This system creates two key problems.
First, the needs of people in wealthy countries trump the needs of people in poor countries. Companies are incentivized to develop products for lucrative markets; by contrast, they have no incentive to develop products that will only serve very small or very poor populations. No incentive exists to prioritize R&D according to disease burden or patient needs.Thinjin Wal, in South Sudan, can tell you just how big this first problem is. MSF has treated three of Thinjin’s sons for kala azar, also known as visceral leishmaniasis. Kala azar is a parasitic disease that infects around 500,000 people each year, and kills 50,000. There are various treatment options, but none are what any patient would want: treatments are highly toxic, take a long time, and require numerous injections.
Thinjin’s sons had to go through a 17-day course of injections. She had to stay with them at an MSF treatment center for several weeks. It was a long way from their village, and the father was left to tend their fields alone. Thinjin recalls that “each day, we have to beg the children to accept the injections. They try to refuse, saying ‘No, it hurts, I don’t want it.’ So I have to take them in each day and make sure they get their injections and hold them when they cry.”

New, more effective diagnostics and treatments are desperately needed to address these neglected diseases and help people like Thinjin and her family.The second problem in the system is that even the diagnostics and medicines that do exist—even the less-than-ideal ones, which we need today while we advocate for better options in the future—are often priced out of reach.
The current best treatment for kala azar is sourced from a single company. Even with discounts, its price is up to 45 times higher than what we need if we are to scale-up treatment to everyone who needs it.Affordability and sustainability are intimately linked with market competition and the existence of multiple suppliers. If new drugs are protected by patents, and if older drugs have only one supplier, the competition that fosters innovation and brings prices down does not exist.

MSF routinely relies on affordable generic drugs to treat TB, malaria, and many other infectious diseases. More than 80 percent of the AIDS drugs that MSF uses worldwide are generics.
Increasing access to generics is therefore vital to scaling up access to health care. Without generic competition, new medications generally remain unaffordable. The most affordable second-line HIV regimen today is still twice as expensive as the recommended first-line regimen. The price of a third-line regimen is more than 14 times higher than the recommended first-line regimen.
Patents are the major barrier to increased generic competition. But they can be challenging to overcome.
In many industrialized countries, intellectual property rights are regarded as sacred. Hailed as drivers of innovation, economic growth, and entrepreneurship, they are vigorously and aggressively defended by powerful institutions like the US and European governments, and by multinational corporations.
However, despite being protected by the strongest intellectual property norms in the world, the R&D productivity of US and European pharmaceutical firms is actually declining.
Large increases in R&D budgets and remarkable advances in basic biomedical research have not yielded an increase in the rate of new drug applications orapprovals.
One glaring example is the empty pipeline for antibiotics. This is widely regarded as a critical danger to public health in both industrialized and developing countries.
The pharmaceutical industry’s response to the so-called innovation crisis is to tighten its grip on intellectual property, and keep the prices of medical products high. But this approach does not stimulate innovation that actually meets patient needs, and must be challenged.
Meanwhile, the industry’s preferred response to problems of affordability is to establish limited, defined discount programs, also known as tiered pricing schemes. However, these schemes are insufficient to address large-scale health problems, they are unsustainable over the long term, and they often fail to address needs of patients in middle-income countries.For example, the data from our latest report on antiretroviral pricing shows that several pharmaceutical companies have abandoned HIV drug discount programs for patients in middle-income countries. Yet today, more than 70 percent of the world’s poorest people—the new “bottom billion”—live in middle-income countries.One alternative to tiered pricing is voluntary licensing.Voluntary licensing enables a form of controlled competition. If it is well-negotiated and well-implemented, voluntary licensing has the potential to enable generic competition and increase access to medicines.However, in practice voluntary licenses are often deeply flawed. Many voluntary licenses are negotiated in secret, and contain anti-competitive and restrictive terms. These licenses actually stifle access to medicines for many people.The work of UAEM in promoting equitable and humanitarian licensing of publicly funded research is of vital importance. It is no small accomplishment that 40 major research universities have committed to openly license globally relevant biomedical research in low- and middle-income countries.

We welcome your successes in getting key universities, like the University of California system, to make public commitments to humanitarian licensing after years of advocacy by UAEM students.
This could allow producers in countries like Brazil, China, and India to manufacture affordable versions of new university-discovered medicines.

Congratulations on these very important achievements, and keep up the good work! We need more commitments from universities, and we also need to start measuring how these commitments are translating into benefits for patients.
MSF aggressively advocates for greater transparency and better licensing terms. We have supported the efforts of the Medicines Patent Pool and have called for all patent holders to join it. We must continue to call for the public release of licensing terms so that these deals can be monitored and evaluated by government and civil society.

But the ultimate step in making newer medications affordable is to remove unwarranted patent barriers altogether.
Under the WTO TRIPS agreement, the world’s most comprehensive multilateral agreement on intellectual property, countries are allowed to define some aspects of patent law and to determine when patent monopolies are warranted.
It’s a myth that every patent application that is filed is valid and represents true innovation.Drug companies routinely apply for patents or are granted monopolies on medicines even when they aren’t actually deserved.This is the issue at the heart of the case between the government of India and Novartis. Indian law explicitly requires that patents should only be granted on medicines that are truly new and innovative. When Novartis applied for a patent in India on its cancer medicine imatinib mesylate, the patent was rejected on the grounds that the medicine was merely a new form of an old medicine, and therefore not patentable under Indian patent law.

Novartis decided to challenge this decision, and the case is pending before the Indian Supreme Court.There have been successful patent oppositions in India, for example when civil society groups contested GlaxoSmithKline's patent application regarding the HIV fixed-dose-combination zidovudine/lamivudine. The group’s success helped to make sure that this combination could be widely used in HIV treatment in developing countries.Last month, MSF launched its online resource to help more people do the same. The Patent Opposition Database will support civil society groups that want to stop unwarranted patents from blocking people’s access to more affordable medicines.Compulsory licensing is another tool that can promote competition and ensure access to medicines. Brazil and Thailand have both used compulsory licenses to deliver important price reductions. India and Indonesia each issued their first compulsory licenses this year. In India, the move brought down the price of a patented anti-cancer drug from more than 5,500 dollars per month to 175 dollars per month—a 97 percent reduction in price.But these legal provisions are under threat. The governments that have used them have regularly suffered from retaliation in the form of threats of economic sanctions and other pressures by US and EU governments and companies.
Furthermore, some governments, including the United States, want to change the rules of the game. They want to incorporate stipulations into regional trade agreements that overturn the public health safeguards in the TRIPS agreement.On your agenda earlier today was a session that covered the Trans-Pacific Partnership agreement and the harmful provisions that the US government is proposing—in secret.One of the most harmful would make it impossible to challenge the validity of a patent before it has been granted.Another would lower patent requirements, so that minor alterations of existing medicines could be given additional protected monopoly status, even if the alteration offers no therapeutic benefit to patients.

The US government is also demanding that diagnostic, therapeutic, and surgical methods be eligible for patenting. This could increase liability for doctors and medical professionals, including MSF doctors working in developing countries. Similar provisions have already been denounced by the World Medical Association, the American Medical Assocation, and the American Orthopedic Surgeons as unethical.

MSF has been actively advocating against including these provisions in the TPP, as well as similar provisions slated for inclusion in other trade agreements such as the one between India and the EU.MSF and UAEM must build a bulwark against the erosion of fundamental rights to health care.
We must work to ensure technology transfer and access to publicly-funded research are not thwarted by commercial interests looking to protect monopolies.

We must encourage governments to exercise their rights under the TRIPS agreement to ensure their populations’ health is not compromised by unwarranted patents.Today, the patient bears the burden of the cost of R&D: if patients can’t afford to pay high prices, the medicines and other medical interventions they need won’t be developed or properly adapted for resource-poor settings.
Listen to Aguil Bol Mallien. Aguil is an MSF patient whose twins were born at Aweil Civil Hospital, in South Sudan. The twins received their first vaccinations before leaving the hospital. Their next inoculations were due in six weeks. But Aguil lives more than an hour’s walk from the hospital, and she was unable to get back on time. Aguil explains, “it's hard for me to carry my twins over the long distance.” She managed to get help from her family and bring her twins in at ten weeks. But she will have to bring them three more times before they turn one to ensure they get the full basic vaccination package.Five visits to a health facility before a baby’s first birthday is prohibitive for caregivers who have to walk for hours or pay for transportation, take time off work, and leave their families for extended periods in order to get to the clinic.
Delivering vaccines to people living in remote areas is incredibly difficult as well. Today, vaccines typically need to be maintained at between 35 and 45 degrees Fahrenheit from the time they leave a factory to when they are administered to a child. Maintaining this cold chain when the outside temperature is 113 degrees Fahrenheit is a challenge. Most developing country governments don’t have the means at their disposal to manage the logistics.
We need more flexible dosing schedules so fewer medical visits are required. We need alternative technologies—heat-stable vaccines, microneedles, inhalation, oral administration—that will allow community health workers to easily vaccinate children, rather than highly trained medical staff in clinics or hospitals.
We’ve seen the success of the oral polio vaccine, which can be administered without any medical training. We need more of the same.

In recent years, there has been a renewed focus on vaccines, which is good. But the focus has been on adding new vaccines to the basic package, not on adapting vaccines and vaccine regimens to the daily reality of patients like Thinjin.Adding new vaccines means that a full course for a child in a country eligible for GAVI funding now costs $38.80 per child, up from just $1.37 in 2001. That’s a 28-fold increase in ten years.Countries are trying to do more with their own resources, but the cost of the newer vaccines is often more than they can finance themselves. A Kenyan ministry of health official equated adding multiple new vaccines to a national immunization program as “taking out multiple mortgages.” When Honduras “graduates” from GAVI support in 2015, it will cost $25.50 just for the rotavirus and pneumococcal conjugate vaccines for one child. Today, with GAVI subsidies, the cost is $1.09.We have established that the system isn’t working for our patients.MSF has been and is trying to remove barriers to access. In 1999 we launched the Access Campaign to stimulate medical innovation for neglected populations and push in other ways to improve access. The Campaign has enabled us to intensify our advocacy, and our efforts to bring about greater transparency, robust generic competition, and better access to licenses and key technologies.We are also going further. There is an urgent need for a new global framework to drive and fund medical innovation in a different way. MSF is advocating for an R&D system that is driven by patient needs.In April this year, an independent expert group at the World Health Organization issued a landmark report.The group recommended the creation of a new R&D framework to ensure that the benefits of innovation are accessible and affordable to patients.One of the key conclusions of the report, and one that MSF supports, is the need to cut the link between the cost of research and the price of medical products.The report recommends including the principle of de-linkage in the design of new innovation incentive mechanisms. MSF agrees. We need mechanisms that stimulate research and development even where there is no profitable market, and that allow the product price to be set according to access needs.


There have been some steps in this direction already. MSF helped set up the DNDi, the Drugs for Neglected Diseases Initiative, in 2003. DNDi is a non-profit drug research and development organization focused on delivering new treatments for neglected diseases. It has already delivered improved treatments for malaria, sleeping sickness, kala azar, and Chagas disease. It currently has two promising drugs in the pipeline that could eventually deliver what we need for sleeping sickness: a medicine that can be taken orally and handed out at a simple community health post.
In partnership with Sanofi-Aventis, DNDi has developed a patent-free malaria treatment called ASAQ that costs just one dollar and has been used by tens of millions of people. ASAQ illustrates how separating R&D costs from product pricing can bring tangible benefits to patients the world over.MSF is also looking into mechanisms such as prize funds. Prizes can be designed to encourage potential innovators to compete to address patient needs, accelerating innovation in a way that separates the cost of R&D from the price of the product.We need a new system to deal with the neglected diseases. We will also need this system to deal with non-communicable diseases. This is the new frontier in global health. Sixty-three percent of all deaths worldwide in 2008 were due to non-communicable diseases. Nearly 80 percent of these deaths—that’s 29 million people—were in low- and middle-income countries. Many of the medicines for cancer, diabetes, and heart disease are currently completely unaffordable for patients living in developing countries.The WHO expert group’s keystone proposal was for member states to start negotiating a global R&D convention that would put in place systems to steer funding and innovation towards the most urgent patient needs.I know that important contributions from UAEM relating to university licensing were included in the final report. Both UAEM and MSF have roles to play as discussions on new frameworks for R&D continue.

Public investment represents the lion’s share of investment in innovative approaches to global health. Public research plays a huge role in drug and vaccine development, and has a particularly huge impact on global health.Pharmaceutical firms have long relied on government and academic institutions for basic research. Faced with high R&D costs and dwindling product pipelines, pharmaceutical firms are increasingly relying on academia to conduct not only basic research, but early-stage translational research as well.UAEM has a key role to play in ensuring that the institutions that are conducting important early stage global health research are pushing the values of equity and access outward to industry and through the development pipeline, all the way to the patient.As the value of public research increases, the role of UAEM in defining how this research is used becomes even more compelling and influential.

Your voices are influential and represent a large and powerful constituency, and I encourage you to be loud and unrelenting in the name of patients like Senzo, Aguil, and Thinjin.You represent the next generation of leaders in global health: you have the opportunity to help solve some of the world’s most intractable health problems.We need to raise the alarm about the dangers of inflexible IP regimes. Let us make sure that the TPP doesn’t set dangerous precedents that will stifle access to medicines and harm millions of patients.We must continue to advocate for more profound changes to the R&D system—to place patient needs at the forefront, and to separate the costs of R&D from product prices. Let us make sure that discussions for an R&D convention are not thwarted before they even start.

New lifesaving drugs and medical tools must not be priced out of reach of the poorest populations. UAEM is already breaking new ground in setting standards for equitable licensing. Let us ensure that products developed based on university research translate into medical benefits for all patients—not just wealthy patients.
We need more attention and resources focused on the needs of patients suffering from neglected diseases. The UAEM project to benchmark universities’ contributions to neglected disease research will provide a strong evidence-based foundation for advocacy in this area.And we need to expand the breadth and diversity of voices with meaningful participation in the access to medicines conversation. In particular, I applaud your work in building the UAEM network in Brazil, and your efforts to expand UAEM’s reach into other regions of the world.We cannot lose sight of the fact that vast numbers of people have failed to benefit from the medical and scientific progress that we have witnessed in recent decades.Together, UAEM and MSF can bring about a better system for global innovation and access to medicines—a system that puts the needs of patients at the heart of the engine driving medical innovation into the next century.


It is a challenge that we can only overcome together—a force for change that unites the collective efforts of doctors, patients, researchers, and student activists around the world.
The stakes are unbelievably high: the lives and well-being of millions worldwide. But the payoff is a more equitable, healthier world.

Thank you.

Enlarged Substantia Nigra Hyperechogenicity and Risk for Parkinson Disease: A 37-Month 3-Center Study of 1847 Older Persons

Berg D, Seppi K, Behnke S, et al

Arch Neurol. 2011;68:932-937

Study Background

If patients with subclinical pathologic features of Parkinson disease (PD) could be identified before they developed symptoms, it could open a window for early neuroprotective intervention.

The substantia nigra (SN) of the midbrain is involved early in the pathogenesis and course of PD, and transcranial sonography has shown that 90% of patients with PD (but only about 10% of elderly control patients) have SN hyperechogenicity. However, it was not previously determined whether SN hyperechogenicity could predict subsequent development of PD in still-healthy persons.

Study Summary

This longitudinal, 3-center observational study prospectively evaluated the association between baseline SN echogenic status and the 3-year incidence of PD in 1847 healthy individuals who were at least 50 years of age. Participants gave a full medical history, had a neurological examination and transcranial sonography, and 1535 of them had a follow-up evaluation. The primary study endpoint was incidence of new-onset PD in relation to transcranial sonography status at baseline.

During a mean observation period of 37 months, there were 11 cases of incident PD. SN hyperechogenicity occurred in 18.7% of the total cohort in whom temporal bone window was sufficient for evaluation, in 17.1% of those who did not develop PD, and in 80% of those who did develop PD. However, only 3.1% of those with SN hyperechogenicity developed PD. Compared with participants who had SN normoechogenicity,

Viewpoint

This prospective study is the first to show a markedly increased risk for PD in elderly persons with SN hyperechogenicity. Limitations of this study include relatively short follow-up period, selection bias, and differing recruitment strategies and ultrasonographic equipment among centers. Nonetheless, transcranial sonography of the midbrain may be promising as a screening procedure to detect imminent PD in appropriate high-risk population groups, particularly because it is noninvasive, inexpensive, and quick and easy to perform by properly trained examiners.

ABSTRACT:

Enlarged substantia nigra hyperechogenicity and risk for Parkinson disease: a 37-month 3-center study of 1847 older persons.

Arch Neurol.  2011; 68(7):932-7 (ISSN: 1538-3687)

Berg D; Seppi K; Behnke S; Liepelt I; Schweitzer K; Stockner H; Wollenweber F; Gaenslen A; Mahlknecht P; Spiegel J; Godau J; Huber H; Srulijes K; Kiechl S; Bentele M; Gasperi A; Schubert T; Hiry T; Probst M; Schneider V; Klenk J; Sawires M; Willeit J; Maetzler W; Fassbender K; Gasser T; Poewe W
Department of Neurodegeneration, Hertie Institute for Clinical Brain Research and German Center of Neurodegenerative Diseases, Hoppe-Seyler-Strasse 3, 72076 Tübingen, Germany. daniela.berg@uni-tuebingen.de

OBJECTIVE: To evaluate whether enlarged substantia nigra hyperechogenicity (SN+) is associated with an increased risk for Parkinson disease (PD) in a healthy elderly population.

DESIGN: Longitudinal 3-center observational study with 37 months of prospective follow-up.

SETTING: Individuals 50 years or older without evidence of PD or any other neurodegenerative disease.

PARTICIPANTS: Of 1847 participants who underwent a full medical history, neurological assessment, and transcranial sonography at baseline, 1535 could undergo reassessment.

MAIN OUTCOME MEASURE: Incidence of new-onset PD in relation to baseline transcranial sonography status.

RESULTS: There were 11 cases of incident PD during the follow-up period. In participants with SN+ at baseline, the relative risk for incident PD was 17.37 (95% confidence interval, 3.71-81.34) times higher compared with normoechogenic participants.

CONCLUSIONS: In this prospective study, we demonstrate for the first time a highly increased risk for PD in elderly individuals with SN+. Transcranial sonography of the midbrain may therefore be a promising primary screening procedure to define a risk population for imminent PD.

Enjoying the life of a physician

Greg Hood, MD, Internal Medicine, 09:51AM Aug 28, 2011

Delayed gratification is the mantra physicians maintain from their time as medical students for years on end. Delayed gratification has its rewards, and its pitfalls. Holding of on the excitements and fun in life can become so ingrained that it becomes second nature, perhaps even first nature. So, how does one enjoy the life of a physician? This is not the issue of what to do with a comparatively high income. This is a question of how to enjoy life. Once the heat on one's life thermostat has been reset for so long it is common to lose a degree of perspective on life. Are others living life this way? Are you missing out on excitement in life? Will you even enjoy the things that you aren't doing in life if you attempt them? Furthermore, are you even able to get motivated to start something new? With its myriad of problems the world can seem to be a disenchanting place. Given the stresses within healthcare as a whole and the lives of physicians (reference the previous two blog entries via the blog's front page) in particular, it is unsurprising that physicians consistently rate at least double the burn out and depression rates of the general population. Some of this is due to cause, such as the personality traits of physicians. As noted in the (unscientific) poll responses for "Marriage and the Business of Medicine" a substantial percentage of responders indicated that "I expend too much effort controlling my emotions rather than sharing them" and "It has always been in my nature to be more comfortably detached from other people". For others it is an issue of effect, or a combination of the two, as noted in the responses for "I commit too much time to achieving success and status to still have time to nurture my personal relationship" and "I'm too burned out to engage in the effort required". Prospective physicians tend to be among the more idealistic of their college peers. They dedicate themselves fully to the long hours and years required to become a physician in their quest to make the world a better place and help their fellow man. Mounting frustration is common in the profession as some find the realities and practicalities of life disenchanting as they pursue what they thought were their dreams. In a sense this should not come as a surprise. If one asks any adult in their 30s, 40s, 50s or beyond what it felt like to be a teenager or how they arrived at decisions and goals as a teen and they will struggle to recall or to relate to themselves as a teen. And yet, the ideals and goals of becoming a physician are the dreams set by teenagers for their adult selves. Perhaps this is one reason for the higher percentage of physicians who are the children of physicians. In spite of a strong domination of physicians discouraging their children to enter medicine in the poll for the blog post "Doctors' children and the business of medicine" the children of physicians understandably have a more realistic worldview of what is entailed in living the life of a physician. Those who do not grow up in a physician household may be more easily dissuaded from pursuing the unfamiliar, rigorous path. It is unfortunately common for physicians, though grateful for what they have and receive, to feel unexcited and unfulfilled. Living a life of service without feeling an inner joy is a damned existence and a tragedy which society as a whole and the physician community in particular must strive to overcome. When the personal and patient care achievements do not gratify one of our colleagues then the very credibility of the dream upon which they have built their professional and personal life comes into question. Physicians are trained to understand many things, and anticipate even more. It is not good as a physician to get a "surprise". We work very hard to keep surprises out of our patients' lives. However, this can bleed over into the rest of life, where nothing is exciting to the emotions any longer, nothing surprising. This tepid existence is an abhorrence to nature, and to those living such lives. How then does one get excited about life? The most difficult questions in life are often the ones that can be so simply and succinctly asked. Of course there is no one answer, no simple answer. There are a number of avenues and steps one may take in life to try to address this fundamental question of the human existence. 1. Make incremental positive changes. At Annual Session the American College of Physicians offers sessions called "Multiple Small Feedings of the Mind". This concept, that small steps for positive change can be effective, is an important one. In order to make dramatic changes in one's life the paradox is that it is the small changes that will often lead the greatest overall change. The steps of eating just a little healthier, exercising a bit more, and others, nourish productive habits, which may grow into ways to get excited about life. Ironically, this approach again smacks of deferred gratification, but it is a familiar approach for physicians and can turn the opponent into a new opportunity. It does take some energy and motivation to get started with these small changes, but not very much. Indeed, if you are reading this article you likely have enough motivation to get started. Just getting started and doing something will give some momentum. Soon those wheels which have been grinding you down will begin turning in the other direction and a positive turn of changes can ensue. 2. Cast out negative thought patterns. Focusing every day on death, deterioration and disease can be a real downer. However, negative thoughts are not the fuel for a fun time. One cannot maintain excitement and enjoy life if this is where the heart is. It truly is a matter of deciding. It is one way or the other. Think back to the positive patient encounters, the ones in which a patient has lost 30 pounds, or has made a meaningful and constructive change in life, based in your advice. How did that make you feel? Taking that seed of positive energy and how it made you feel and focusing your daily mental energy on feeling like that will not only help you, but help your patients as well. 3. Seek the silver lining. There is a lot to be negative about in internal medicine, for example. However, it is important with each patient to seek the positive. Finding the small victories in life can be very powerful for endurance within this profession. Heart trouble is a major killer still, yet we have ways through our advice and prescriptions that we can make the patient more comfortable, and more likely to live to see their daughter graduate. Antibiotic resistance is a terrible problem, but still every day we help people live through what would have been fatal infections a few years ago. The EMR server is down, but this is an opportunity to go for a walk with the family. 4. Exercise. Some believe exercise should be a four letter word. Nevertheless, it is something our bodies were built to have. Sitting on the Chesapeake in a sailboat with no sails is no fun. Sitting in the middle of life and not moving/exercising isn't either. Negative energy goes into peoples' thoughts about their appearance, their energy, their health problems and mortality. The number one, most effective treatment for over 85% of the health problems I see in the office is daily aerobic exercise. The most effective means to reduce or eliminate most medications I prescribe every day is daily aerobic exercise. The human body was designed for seven to twenty four hours of aerobic exercise each week. Starting with what one is capable of today, and building up to a minimum of seven hours a week is life changing, life-energy changing. 5. Value loved ones. As noted in the last two blog entries family members are integrally involved in our lives, and as such, the success of the business of medicine. Showing those in your life that you value them, investing time and energy in them will help you, both in the short and the long term. It gives them an opportunity to show you their returns to you. It also allows you to see life stages and life experiences from other points of view. 6. Rediscover your hobbies. Whether it is an income producing hobby or not there is value from doing off-career-topic hobbies that you love. If building furniture or painting is your hobby and it brings you income then that's the cherry on top. Reading, playing music or modeling for your own pleasure is a worthwhile investment of time and life energy because it injects energy into your life. If you don't have a hobby that you are passionate about then start exploring and trying new ones until you find yours. 7. Surround yourself with excited people. Working with competent but negative people is perhaps the biggest negative secret in the business of medicine. No one can destroy the energy and morale of a practice like a jaded, faded negative coworker. By contrast, when you work with excited people, and feed excited energy in yourself, the experience changes completely. 8. Make a point to recharge. Sometimes the drained unexcited feeling can't be shaken. This is an important time to take a break, even from your usual recharging or vacation activities. Use the frequent flier miles to go to Bermuda instead of selecting more free magazines for the waiting room. Go somewhere you haven't been before. There are often great places within your state to go - that you've never been before. When we were in California Sequoia National park became one of my top three favorite places on Earth. Getting somewhere new, somewhere completely different is a way to decompress one's perception of time again. Events which adults are familiar with are routinely perceived to take minutes or seconds whereas to children experiencing the same thing for the first time it feels like hours. This is called time perception compression. If you allow yourself to experience wholly new experiences then you have the opportunity to slow the pace of life down, and see it through more of a child's eye again. 9. Accept feedback. Most physicians don't like feedback, or at least have trouble accepting and believing positive feedback. They sense that there is another shoe out there that might fall... someday. Each person on this planet is mortal, so yes, one day even the patient with the most remarkable "save" you have made will still die. But positive feedback is positive energy, encouragement. It is a gift back from the patient to carry you a little farther in life. When you get negative feedback, if it is constructive, then use it to get better. If it is hateful, which is rare, then keep perspective that it is a personal tragedy in that person's life that their soul is so diminished. When you receive praise practice accepting it, letting it sink in, rather than just expressing gratitude and not letting the other person's positive energy truly touch you. 10. Help others. Many physicians ultimately find their positive energy in mission trips, overseas and otherwise. There is a lot to be negative about in such travel, the jetlag, the disease, unsanitary and distasteful conditions. Yet, one never hears those who do engage in such trips coming back drained or disheartened. Rather, the ways in which they help others, whether trivial or life-changing, infuse so much positive energy in their lives that no burdens inherent in the delivery of the service are able to detract from the experience.

Vampire Bat Causes Fatal Rabies Encephalitis in USA

Andrew Wilner, MD, Neurology, 10:46PM Sep 1, 2011

Deadly Bat Bite A flurry of fictional vampires has recently invaded American television, movie screens, and bookstores. While the Centers for Disease Control and Prevention (CDC) offers no statistics on vampire attacks, the CDC did report the first case of fatal rabies in the US from a vampire bat (August 12, 2011). Fruit Bat just hanging around...(photo AW) Clinical History According to the patient's mother, the 19 year old boy had been bitten by a bat on the left foot while sleeping in Michoacan, Mexico, before coming to Louisiana to work as a laborer on a sugar cane plantation. After one week of work, he developed generalized fatigue, left shoulder pain, and left hand numbness. Initially, his symptoms were attributed to overexertion. He then experienced hyperesthesia of his left shoulder, left hand weakness, generalized areflexia, and drooping of the left upper eyelid. A presumptive diagnosis of the Miller-Fisher variant of acute inflammatory demyelinating polyneuropathy (Guillain Barre) syndrome was made. He became febrile, had respiratory distress, and lapsed into a coma. A lumbar puncture revealed 87 WBCs (97% lymphocytes) and a protein of 233 mg/dL. Rabies virus specific immunoglobulin G and immunoglobulin M were present in the CSF. Rabies virus antigen was detected in postmortem brain tissue, and antigenic typing isolated the vampire bat rabies variant. I chatted with Brett Petersen, MD, MPH, Medical Officer, Poxvirus and Rabies Branch, CDC, who was kind enough to answer my many questions. He told me that this case is unusual because vampire bats are only found in Latin America, not in the US. Dr. Petersen explained that patients may develop hypersalivation and hydrophobia due to painful laryngeal spasms. "Even the sight of water can create pain," he stated. According to Dr. Petersen, bat rabies is uniformly fatal, even for infected bats. However, the long incubation period of the virus allows it to be transmitted from bat to bat. In human cases, the median incubation period is 85 days. In general, for a person to be infected with bat rabies, the virus must be inoculated under the skin from the bat's saliva. This requires a bite or a scratch (Hooper et al. 2011), although infection by aerosolized virus has been proposed. Rabies is caused by a Lyssavirus and has the highest case fatality of any infectious disease (Blanton et al. 2010). With rare exceptions, every patient dies. Vampire Bats Characterized by big ears and razor sharp teeth, vampire bats feed at night, quietly landing or jumping onto their prey. However, because of the bat's padded feet and wrists, the victim may be unaware of the bat's presence. Heat sensors in the bat's nose detect accessible blood vessels close to the skin's surface. The bat has an anticoagulant in its saliva that allows it to lap up blood with its tongue. After feeding for approximately 30 minutes, the bat may have ingested so much blood that it is barely able to fly. Victims may not realize they have been bitten. Bat teeth are very fine and may leave only pinpoint puncture marks <1mm that may be nearly undetectable (De Serres et al. 2008). In the past 20 years, most of the people infected with bat rabies did not report a bat bite (De Serres et al. 2008).  The number of rabies cases in the US has decreased dramatically due to the elimination of canine rabies by vaccination programs for dogs. Rabies now comes from wildlife such as raccoons, bats, skunks and foxes (Blanton et al. 2010). This is in contrast to the global situation, where rabies kills approximately 55,000 people per year, mostly due to rabid dogs (De Serres et al. 2008). Humans are not natural reservoirs for rabies virus (Hooper et al. 2011). Since the elimination of dogs as a rabies reservoir in the US, bat rabies has become the most common cause of human rabies. In 2009, only 4 cases of rabies were identified in the US. Of these, 3 were due to bats. A fourth case of rabies was in a physician who had been bitten by a rabid dog while traveling in India. Vampire bats are the leading cause of human rabies in Latin America. One concern about global warming is that it could possibly affect the range of vampire bats, introducing them into the Southern USA, resulting in an increase in bat rabies. Post-Exposure Prophylaxis Over 20,000 people receive rabies post-exposure prophylaxis in the US each year, and there are no reported failures (Hooper et al. 2011). The purpose of post-exposure prophylaxis is to prevent the virus from reaching the central nervous system. While the neurotropic virus travels through peripheral nerve axons to the central nervous system, there is no clinical evidence of infection. Post-exposure prophylaxis is 100% effective if administered before symptoms develop. However, once the rabies virus has entered the central nervous system and caused symptoms, the outcome is nearly always fatal.   The current recommendations for postexposure prophylaxis are 4 doses of rabies vaccine and 1 dose of rabies immunoglobulin. The wound should be vigorously cleaned and infiltrated with rabies immunoglobulin. The immunoglobulin provides immediate protection while the vaccination induces endogenous antibodies. While the older rabies vaccine was made from nervous tissue and was painful, the current vaccine is made from human diploid cell culture or purified chick embryo cells and is no more painful than other vaccines. In 2008, the CDC revised its vaccination guidelines from 5 shots down to 4, administered on days 0 (right away), 3, 7, and 14. Allergic reactions are infrequent (1/1000), but patients should be closely supervised (De Serres et al. 2009). Persons with altered immunocompetence should receive the older 5 dose regimen. If work or travel predispose individuals to rabies exposure, they can be vaccinated prophylactically. There is also research on an intranasal vaccine (Cruz et al. 2008). Conclusions: For those who have received excessive exposure to vampires from TV, cinema and other media, their suffering may continue, as a vaccine is still unavailable. However, if one is bitten by a bat, the CDC recommends the following: 1. If the bat is available, test it for rabies. If the test is negative, no anti-rabies prophylaxis is needed. 2. If the bat flies away, assume it was rabid and administer post-exposure prophylaxis according to the CDC guidelines. 3. Treat as soon as possible after the bite. Rabies, although rare, should be considered in the differential diagnosis of unexplained acute, progressive, encephalomyelitis. Because of the relatively long incubation period of the rabies virus, a travel history should be obtained from the patient because of the possibilty of infection outside the US. Prompt post-exposure treatment is critical-once a patient has developed symptoms, there is no established therapy (Jackson 2011).  More information on bat rabies can be found on the CDC rabies web page. References Blanton JD, Palmer D, Rupprecht CE. Rabies surveillance in the United States during 2009. JAVMA 2010;237(6):646-657. Cruz ET, Romero IAF, Mendoza JGL et al. Efficient post-exposure prophylaxis against rabies by applying a four-dose DNA vacine intranasally. Vaccine 2008;36:6936-6944. De Serres G, Skowronski DM, Mimault P et al. Bats in the bedroom, bats in the belfry: Reanalysis of the rationale for rabies postexposure prophylaxis. Clinical Infectious Diseases 2009;48:1493-9. De Serres G, Dallaire F, Cote M, Skowronski DM. Bat rabies in the United States and Canada from 1950 through 2007: Human cases with and without bat contact. Clinical Infectious Diseases 2008:46:1329-37. Hooper DC, Roy A, Barkhouse DA et al. Rabies virus clearance from the central nervous system. Chapter 4 Advances in Virus Research 2011;79:55-71. Jackson AC. Therapy of human rabies. Chapter 17 Advances in Virus Research;79:365-372.

A Misdiagnosis: Sleepiness and Severe Headache

Mark Crislip, MD

Authors and Disclosures

Posted: 09/02/2011

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Clinical Presentation

A 28-year-old Gambian man presents with progressive headache and lower-extremity weakness.

History and Physical Examination

History. The patient's progressive headache started 2 weeks prior to admission. It slowly advanced from mild to severe and constant and became global with photophobia and a stiff neck. Five days prior to admission he was seen in the emergency department where, after a lumbar puncture, he was told that he had viral meningitis (it was September, enteroviral season). For 2 days prior to admission he had had progressive lower-extremity weakness.

• Review of symptoms: no constitutional or other symptoms
• Remote medical history: none
• Medications: none
• Allergies: none
• Habits: none
• Pets: none
• Diet: regular
• Travel: born and raised in rural Gambia; has been in the United States for about a year
• Social: married; no children
• Immunizations: up to date
• Sports/water exposure: none
• Infectious disease exposure: PPD negative 3 months ago

Physical examination. On physical examination, the following were noted:

• Vital signs: temperature: 97.9º F; pulse: 89 beats/min; respirations: 20 breaths/min; blood pressure: 126/67 mm Hg
• General: sleepy but arousable
• HEENT: normal, except for stiff neck
• Lungs: clear
• Heart: normal
• Abdomen: nontender without masses or organomegaly
• Extremities: normal
• Skin: multiple scars
• Neuro: oriented to person, place, and time. Sleepy but responds appropriately. Cranial nerves intact. Upper extremities normal. Proximally in the quadriceps and iliopsoas muscle strength was 5/5, and the patient was able to bear weight and ambulate. Cerebellar examination was normal for finger-to-nose testing and he had bilateral positive Babinski (upgoing toes) sign. Reflexes were 1+ in the upper extremities, 2+ at the right knee jerk, 1+ at the left knee jerk, 2+ at the ankle, with 2-3 beats of clonus. Tone was normal without atrophy or vesiculation. Gait was wide-based. Tandem gait could not be performed.

Diagnostic Evaluation

Lab results. The following results were obtained:

• WBC: 4 x 10³/mm³
• Hgb: 10.9 g/dL
• Differential: normal
• Hemoglobin A1c: normal
• Glucose: 105 mg/dL
• Bilirubin: 0.3 mg/dL
• Calcium: 8.5 mg/dL
• Albumin: 3.2 g/dL
• Total protein: 10.4 g/dL
• Alkaline phosphatase: 78 U/L
• ALT: 25 U/L
• AST: 36 U/L
• Urinalysis: normal

Lumbar puncture

• CSF collected before admission: WBC 254 x 10³/mm³ with 9 RBCs, 42 neutrophils, 42 lymphocytes, 16 monocytes. CSF glucose: 11 mg/dL. CSF protein: 185 g/dL. Gram stain negative.
• CSF collected upon admission: WBC 112 x 10³/mm³, similar differential, CSF glucose 21 mg/dL, and CSF protein 234 g/dL.

Diagnostic Imaging

• Chest x-ray: clear
• MRI of spine; radiologist report: "Enhancement of CSF consistent with inflammatory change. No focal lesions observed. No focal enhancement. No evidence of a cord compression. When images before and after infusion of paramagnetic contrast are compared, there is fairly gross enhancement of the CSF in the thoracic and lumbar portions of the spine. This is less obvious to nonexistent at the cervical level and in the vicinity of the craniocervical junction."

What is the cause of the patient's granulomatous meningitis and weakness?

Mycobacterium tuberculosis

Meningovascular syphilis with transverse myelitis

African sleeping sickness

Histoplasma capsulatum var. duboisii, African histoplasmosis

Cryptococcus gattii

References