Today’s Agenda: World Health Assembly General Elections

Today I report to you from the Palais du Nations in Geneva where a secret ballot is currently being held for the new Director General of the World Health Organisation.

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Margaret Chan’s decade tenure has drawn to an end. Dr Chan will leave a strong legacy without a doubt, as did many before her. And today’s events and outcomes may have a profound role in defining the next 10 years in global health and indeed, the direct of leadership for the bulk of the SDG era.

World Health Organisation (WHO) Director

Who will it be?

Cheers,

Christiana

Seven lessons I learned from Professor Hans Rosling: A Tribute

Last week we lost one of the greatest statisticians of our time. A clinician who informed scholars and audiences world over; and a researcher whose work on economic development and global health changed the way we view our world. Personally, too, I have lost a role model, Dr Hans Rosling of the Karolinska Institute.

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Nonetheless, Dr Rosling’s memory, influence and legacy remain with us.

He inspired me; and my serendipitous exposure to his work played a major part in making me who I am today. Not only did Dr Rosling’s work in the fields of public health and economic development inform audiences world over, but his dedication and contribution to informing professionals, pharmaceutical companies, public health workers and laypeople across the globe will not soon be forgotten.

So, in tribute, this article will memorialize the seven major lessons I learned from listening to and reading the work of Professor Hans Rosling.

 

  1. “We live in a one hump world”

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Figure 1: Asian countries, including Australasia are shown in pink; African nations in blue; Americas in green and European nations including Turkey, in yellow. The y-axis represents population.

 

The long-term readers amongst you will know that I am a proud South African. A member of the BRICS – the large, emerging, middle income powers of the world. The “nearly theres but not quite”, to some.

Using data and the excellent visuals generated by his Gapminder foundation’s revolutionary software; Dr Rosling demonstrated to us how so many of our traditional views on wealth and wealth distribution are in fact outdated.

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Figure 2: For comparison, the graph above represents the world in 1975. Over 50% of the world’s population lived in extreme poverty, and the vast majority of these were in Asia. There was a clear disparity between wealth in the traditional west and the rest.

 

The vast majority of the world are not only out of poverty, but earn almost the same amount of money as measured by US$/day, regardless of where they live. Understanding this is vital to interpreting our world and understanding healthcare challenges.

 

  1. Let’s stop using the terms “Developing and Developed” to describe nations

In the same vein, on occasion, Professor Rosling mentioned that the terms developed and developing are not particularly useful in describing the world we live in today. Many of these terms are understandably established along political lines and regional categorizations. Nonetheless, their use is of minimal benefit.

We live in an incredibly rapidly changing world; the most peaceful two decades in recent history in terms of war with the highest global life expectancy. Globalisation, decolonization and the slight dismantling of national and geopolitical protectionist trends in recent decades have opened opportunities for previously suppressed and disadvantaged nations world over. It is my hope that what we are witnessing in this digital and globally connected era is the beginning of the democratization of trade, health and wealth. 

 

  1. Humans never lived in ecological balance with nature: they died in ecological balance with nature.

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The world is getting better; not worse.

There has never been a better time for human life and civilization in known history as now. Today, globally, we live better than ever before**; longer than ever before; have fewer children whose chances of survival to reproductive age is the highest rate in recorded history.

If you didn’t know this, you’re not alone. Not only does fear mongering sell; but parents and teachers inform young people based on their experience of the world as it was when they were young, including ideas that their teachers and parents imparted to them.

 

  1. Population growth is inevitable

Professor Rosling is arguably best known for his views, supported by statistical projections, on population growth.

The “population growth is the problem” argument has always been a personal pet peeve. But I’ll write more on this in future.

The global population will likely reach 11 billion before reaching a plateau. This is not because more people will be born; but rather that the additional 3.5 billion people are already alive.

Dr Rosling often demonstrated this in a very accessible way with the use of plastic or Styrofoam boxes. He referred to this concept as the global population ‘fill up’.

In short, today very few people die between infancy and the age of 65. Thus, as we are having only enough children to roughly replace ourselves, the population will not grow from new births: it will grow from later deaths. The global population fill-up of adults.

“We have reached the age of Peak Child” (2014)

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  1. The future will be dictated by love, not fear.

Child mortality is the primary driver of fertility rates. The number of babies per woman only decreases when the chances of child survival increase. When families are uncertain of the chances of survival of their children, they will have more children. Today, the global average number of babies per woman is 2.4. In Vietnam, the average number of babies per woman is 1.7. In Bangladesh, 2.14. In Yemen, 3.83 and 2.34 in South Africa.

Many make assumptions about fertility rates based on the world as it was in the 1970s. Rich countries had long life and small families whilst poor countries had shorter lives but larger family. This simply is not the world we live in: the world we live in is changing rapidly; and continues to do so.

Dr Rosling spoke on how most young couples today have access to some form of contraception; and with time and changing social norms; family values have started to shift towards an increased importance of how well one’s children are doing as opposed to how numerous they are. This is how love will dictate the composition of families, rather than fears based on child and infant mortalities.

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  1. We need to use useful metrics

A good example of a metric that is commonly used to discuss global disease profiles is the percentage of adults within a particular population living with HIV.

This is not a particularly useful metric. In a nation such as South Africa, Antiretroviral Treatment is free to any person or persons presenting themselves at a clinic or hospital. Moreover, whilst highly costly, budget provisions have been made for on-going counselling and lifetime maintenance of treatment and management of disease including co-infections. Thus, a large proportion of HIV positive individuals have been able to receive the treatment to live a long and healthy life. Indeed, provided that there are newly infected individuals, the number will continue to rise, and this is only a sign that those who contract HIV are surviving: not progressing to AIDS or succumbing to other infections.

This is an example of a middle-income country. Contracting HIV in a low-income country can be very different. Often, people who contract HIV in low-income, very low income or some land locked developing states, do not survive unless they have the personal funding to give them access to treatment. In some instances, free treatment is made available for periods of time but without the consistency vital to antiretroviral therapy. Such a nation may have a lower percentage of infected individuals due to survival rates. Thus, this metric is not particularly useful, nor encouraging.

I might suggest more useful metrics to communicate the same data in a stronger way. Perhaps “% HIV positive patients on ART for >2 years”; or “% HIV positive patients progressing to AIDS”

 

7. Healthcare spending is more important than GDP in dictating national public health outcomes

Wealth does not need to precede health (see: Vietnam; Cuba), but it sure does help. Strategic allocation of resources both between and within nations can act as a major driver of positive health outcomes even at a relatively low GDP, middle-income nations can create conditions to ensure long length of life.

The challenge faced by many of such nations that are winning the fight against communicable disease is the dual burden created by the fast emergence of a range of non-communicable diseases coexisting alongside traditional disease profiles. I have written about this in the past here.

These governments face the challenge of the incredible financial challenge of dealing with NCDs such as cancers, cardiovascular diseases, kidney failure and diseases of old age such as Parkinson’s disease and Alzheimers. Thus, time will tell if strategic efforts in prevention of these in many nations will yield useful results, or if, indeed, a third paradigm shift will occur in the management of NCDs in low and middle-income nations.

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*All graphs used were taken from Gapminder.org, the foundation started by Professor Rosling and his son, Ola Rosling, dedicated to the democratization of economic and health data and statistics.
**As measured by the percentage of the global population percentage currently living under “extreme poverty”.

Hans Rosling: A Tribute

Such sad news, the death of such a great man. May his legacy and influence live on. As a clinician, as a statistician who informed scholars and audiences world over, and a researcher whose work on economic development and global health changed the way we view our world. It’s hard to lose a role model but I can’t help but feel he was lost too soon. RIP Dr Hans Rosling.

I feel that it’s apt to share one of his oldest (but still my favourite) TED talk. He was a clinician and statistician whose research and accessible insights changed the way we view the world, and our understandings of the complex relationships between development and health.

The Best Stats You’ve Ever Seen

This weekend I will be posting the top seven lessons I learned from Dr Rosling over the years, in the hope that these are the concepts he might wish not to be forgotten. Find that article here.

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Rethinking Rabies: A Breakthrough in Management? – My comments on the literature

Let’s talk about disease management:

Rabies is a vaccine-preventable, zoonotic disease of global concern, resulting in over 55 000 deaths annually. Whilst standard post-exposure treatments are estimated to prevent hundreds of thousands of fatalities, these are not without shortcomings. Recent immunological research into novel treatments has revealed promising results. Published in the Journal of Infectious Diseases, the research paper this article comments on has been described as groundbreaking. (I dare say, most notably by those enchanted by the spell of the [magical] monoclonal antibody: still one of the coolest cocktail party topics in immunology.)

 

The article by van Dolleweerd et al can be found here.

Overview

So let me break it down. Dog bites make up 99% of rabies virus (RABV) transmission from animals to humans. RABV infection usually results in death from the onset of clinical symptoms. Endemic in some regions, rabies is a concern in over 100 countries, particularly in Asia and Africa. Primary prevention is vital to combatting rabies globally. The World Health Organization (WHO), working with governments and NGOs, strongly recommend widespread canine vaccination as the most effective means of rabies prevention.

Secondary prevention treatment of suspected cases is Rabies Post-exposure Prophylaxis (PEP): a combination of the rabies vaccine and rabies immunoglobulin (RIG). Unfortunately, RIG preparations can be costly, varied or even contaminated, particularly in lower resourced settings. Furthermore, immunoglobulins lack the epitope specificity of monoclonal antibodies (mAbs), often resulting in adverse reactions.

A major new research breakthrough to replace RIG is a cocktail of mAbs, particularly including the engineered, plant-expressed, chimeric mAb, E559, shown to successfully neutralize RABV in-vivo. This article highlights the latest scientific findings, reviewing the relevance for future management of suspected rabies virus infection.

 

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Limitations of PEP

Currently, survival post exposure to RABV is based solely on the administration of PEP. Classified by WHO as a Neglected Tropical Disease, RABV has been shown to disproportionately affect impoverished communities. Furthermore, RIG is often subject to environmental challenges associated with storage and contamination.

Polyclonal serums such as RIG, from vaccinated donors, are subject to the risks associated with the use of human blood-derived products, such as potential transmission of infectious agents if appropriate measures are not observed and unpredictable availability of donors. They are also susceptible to batch-to-batch variability. The majority of virus specific antibodies contained within the serum are non-neutralizing, with a small percentage being pathogen specific. Moreover, only human and equine polyclonal immunoglobulins, HRIG and ERIG respectively, are available.

The exciting development and benefits of new monoclonal antibody preparations to replace RIG is that they are highly effective due to their epitope specificity, neutralizing a range of RABV isolates, with minimal adverse effects.

A little lost?

 

The bottom line is that Rabies Virus disproportionately affects impoverished communities and PEP as treatment is effective but easily compromised, as human/horse blood derived products can be, particularly where storage infrastructure is variable.

 

Monoclonal Antibodies for Treatment

Monoclonal antibodies (a.k.a mAbs for to coolest of us) remain a new frontier for modern therapeutics. In 1986, the United States Food and Drug Administration (FDA) approved the first monoclonal antibody drug, Muromonab-CD3, to prevent organ rejection in kidney transplant patients. Today, almost 30 mAb drugs have been approved, with many more undergoing clinical trials.

Derived from a single cell line, a hybridoma, produced by the fusion of a single B-lymphocyte clone and a myeloma cell; mAbs have the advantage of greater specificity than polyclonal antibodies, derived of multiple B-cell lineages. These mAbs directly neutralize rabies virus glycoprotein (RVG) by inhibiting RVG binding at viral receptors as well as inhibition of attachment and fusion at the plasma and endosomal membranes, respectively.

A major advantage in the development of rabies treatment using mAbs has the potential for widening access in endemic areas. Earlier research into mAbs for treatment of RABV, human mAbs, showed promising therapeutic results in in-vitro neutralization of particular RABV strains. Moreover, in- vivo experiments in hamsters found that two human mAbs showed equivalence to HRIG in preventing rabies virus. Where this approach was found lacking, however, was cost- efficiency.

Van Dolleweerd et al, successfully cloned and engineered a plant- produced candidate monoclonal antibody, E559. The chimeric antibody, an isoform of E559, was equally effective as commercial HRIG in a hamster model.

Comparing two monoclonal antibody production platforms in plants to murine hybridoma-derived platforms; the paper found that whilst plant- derived vs. mammalian-derived mAbs have different half-lives, there is no difference in rates of RABV neutralization.

Moreover, decreasing production costs by improving the productivity of cell lines and developing transgenic tobacco plants as well as tobacco cell cultures to express E559 has made the use of mAbs in treatment of disease, even in the poorest settings, a feasible alternative to existing secondary prevention models for RABV.

Whilst the use of mammalian mAbs is virtually not viable in lower resourced settings; the promise of tobacco plant- derived RABV neutralizing mAbs presents the possibility for greater accessibility as well as production capacity in rabies-endemic regions.

How relevant are these developments in the future prevention of Rabies Infections?

The high levels of efficacy of PEP made it the main post-exposure treatment for RABV for decades. In this respect, concerns surrounding access and cost were primarily addressed in three ways: developing models of categorization of levels of exposure for treatment allocation; broadening availability of the less costly equine RIG, despite increasing scarcity; and the modification of administration modes: particularly from intramuscular to intradermal.

In this respect, the introduction of monoclonal antibodies to the RABV prevention debate was met with initial skepticism. MAbs, although newer and highly promising, were infamously expensive to produce. Further, their use requires higher levels of skills and technology. This resulted in a view that mAbs would only be useful in regions where administration of standard PEP is highly feasible and rabies exposure is relatively rare. This background underlines the significance of cheaper, plant-derived, potential mAbs to replace RIG.

However, RNA viruses, such as RABV, lack mechanisms to prevent the emergence and proliferation of mutant strains under exposure to highly specific monoclonal antibodies. Thus, to be effective, an immunoprophylactic needs to be able to neutralize a range of RABV isolates: an integral quality of any effective mAb treatment for RABV.

In this regard, more scientific research in this direction going beyond E559 is required. A single mAb is unlikely to provide sufficient protection across a broad range. Initiating the use of plant-derived mAbs, as demonstrated by van Dolleweerd et al, is the first step in dismantling the prohibitive frameworks within which mAb treatments have long existed. This will pave the way, for better results and broader opportunity for mAb use in response to RABV exposure; and also for mAbs in treatment of other neglected tropical diseases globally.

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Have a banging Thursday!

-Christiana

 

Reference: “Engineering, expression in transgenic plants and characterisation of E559, a rabies virus-neutralising monoclonal antibody.” – van Dolleweerd et al, July 2015

 

Coming soon: Rethinking Rabies. A Breakthrough in Management?

Rabies is a vaccine-preventable, zoonotic disease of global concern, resulting in over 55 000 deaths annually. Whilst standard post-exposure treatments are estimated to prevent hundreds of thousands of fatalities, these are not without shortcomings. Recent immunological research into novel treatments has revealed promising results.

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More on this later this week. 

For now, have a stellar Monday!

– Christiana

This week: On the Age of Gender Equality

SDG 5: Achieve gender equality and empower all women and girls

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“We need to empower women. Give women a voice in the decision-making process. Give women a political voice where they can champion, for their own welfare. And, of course, for us. United Nations – organizations, agencies – we need to do our part.” – Margaret Chan

Have a great Monday!

– Christiana

 

Médecins Sans Frontières Scientific Days 2016

Today I attended the second day of the annual Médecins Sans Frontières / Doctors Without Borders Scientific Day.

I have been thoroughly impressed not only by the entire program this year but also with the dedication to broadening access to healthcare, improving diagnostic systems and achieving the objective of the democratisation of health through the development of accessible and appropriate technologies. E-health, digital health and telemedicine – for far too long it has been assumed that these are not feasible, viable modes for use in low and middle income countries. And this is simply not the case.

I commend MSF and the global health community for their dedication to e-health. I’m excited by the changes in the global health landscape: the world is changing rapidly and (fortunately) we, in health, are keeping up!

Next stop: My first ever TED event tonight!

Yours truly,

Christiana