SERIES: Rising incidence of obesity in the United Kingdom – Introduction

In the past three decades obesity in the United Kingdom has increased three-fold, emerging as one of the UK’s most prominent public health challenges. Obesity is largely a lifestyle and behavior associated condition, although there are also some genetic factors.

Obesity is measured by a standard anthropometric measurement of known as Body Mass Index (BMI). The terms overweight and obese are usually classified as increased weight-for-height. The figure below classifies the BMI ranges used to define BMI status. (Do you know your BMI?) BMI is calculated by dividing the weight in kilograms by the square of the height in meters. (Or googled)


An individual whose weight is two or more times the ideal weight is classified as morbidly obese.

Recent studies show steady increases in obesity incidence both nationally and internationally. Indeed, today we live in a world where more people are clinically obese than those suffering morbidity or mortality due to starvation.

Globally, the percentage of people classified as overweight or obese increased in both men and women from 28.8% and 29.8% in 1980 to 36.9% and 38.0% respectively. Child overweight and obesity also increased. In 2013, World Health Organization adopted a target of halting the rise in child obesity by 2025.

The primary reason obesity is a public health concern is because it is a risk factor for other non-communicable diseases (NCDs) such as Type II Diabetes Mellitus (T2DM), hypertension and coronary heart disease (CHD). Morbid obesity, considered the most serious stage of obesity, can leave patients at the highest risk of mortality related to their obese status.


Throughout this series I will outline the causes and consequences of rising obesity incidence as identified in empirical studies and literature. All sources are available upon request.

Likely due to methodological challenges, much of the available data on obesity in the UK and elsewhere discuss prevalence and not necessarily incidence. However, understanding disease prevalence and its nuances is useful in interpreting both causal and consequential factors of incidence.

 According to Health Survey for England (HSE), in 2013, 26% of men and 24% of women were classified as obese; 41% of men and 33% of women were classified as overweight. Scotland and Wales had similar findings.

The UK has seen increases in obesity in children for several years. In 1995, 11% of boys and 12% of girls were classified as obese. By 2005, these numbers were 18% and 19% respectively. These increases have since leveled off: to 16% of boys and 15% of girls in 2013.

The prevalence of obesity is significantly higher in some groups. Children were more likely to be obese if they lived in an urban area. Whilst 22% of boys and 21% of girls from the lowest-income families were already obese.

Rising incidence of obesity is a problem

The major problem presented is the co-morbidities with which obesity is associated. Obesity is a major risk factor for many NCDs, thus causing and contributing to a high proportion of morbidity and mortality.

Type 2 Diabetes Mellitus (T2DM) is strongly correlated with obesity. The detrimental effects on an individual living with obesity and T2DM are multiple-fold. Rising incidence of obesity in children is well correlated with incidence of childhood T2DM. Expectedly, in terms of reducing the risk of cardiovascular diseases, particularly coronary heart disease, greater reduction in adiposity results in greater risk reduction. With the exception of LDL cholesterol, fat loss in obese patients improves blood pressure, glycemic control and lipids.

T2DM is simply hyperglycemia resulting primarily from a resistance to insulin but also from impaired insulin secretion. Clinical studies have shown the metabolic effects of high sugar, particularly fructose. These sugars mediate fatty liver and insulin resistance in humans. In a typical Western diet, the majority of fructose comes from sugary, soft and fruit drinks, often resulting in significantly elevated levels of fasting glucose and thus, high levels of insulin, leading to resistance.

Obesity also has a role in worsening nocturnal hypoxia in obstructive sleep apnea syndrome (OSAS). It has been theorized that oxidative stress and inflammation caused by OSAS is a major factor causing cardiovascular morbidity and mortality in obese patients.

This series will explore the causes, consequences and some potential solutions to rising obesity incidence in the UK. The significant contribution of behavioural factors to the rising prevalence and incidence of obesity suggests an important role for well-defined interventions to manage and reduce obesity levels. It is clear, however, that the burden and cost of the consequences of obesity justify the need for the United Kingdom to aspire to meet its own targets and those set by the World Health Assembly.



Challenges Facing the South African Pharmaceutical Industry


As some of you may already know I am a firm and unapologetic believer that the partnership of NGOs, national and international health governance with the pharmaceutical industry, rather than its exclusion, is vital to the effective treatment of disease globally.

From my first experiences at intergovernmental organizations at the age of 16, I came to appreciate the importance of medical research in global health. I have interned at the World Health Organization on two occasions but my experience at Tropical Diseases Research in particular, working with an infectious diseases specialist, designing educational tools for community healthcare workers on the use of a rectal artesunate drug for infants with severe malaria, I realized the need for innovation in the design of drugs and drug delivery systems.

I don’t believe that big pharma is the enemy. I believe the industries of biotechnology and pharma are an invaluable resource; and that the market failures we encounter at scale are primarily a function of the market forces that govern every industry in our world today.

The fact is that the profitability of drugs and vaccines has been a primary driver in the development of the life saving treatments available today. As for those that have fallen through the ‘gaps in the market’, so to speak (see: Antimicrobial resistance; Alzheimer’s, Malaria), I will write on this in future.

  1. HIV: South Africa is doing pretty damn well dealing with the burden of disease

South Africa is a BRICS nation: the growing, middle-income giants of the world. It was the first nation in the world to make Antiretroviral treatment free to all HIV positive individuals at the point of presentation in 2001. Moreover, today, it’s virtually impossible to visit a clinic or hospital in South Africa without being tested for HIV – this means that infections are detected more rapidly than ever.

The result of this is excellent ARV coverage, bearing in mind that this is a lifelong treatment, and HIV positive individuals today live as long as the general population. What this also means is that the nation still has the second highest HIV infection rate globally. Not because management has been poor; but because unlike in many smaller African economies, a sizable proportion of HIV positive patients diagnosed in the mid 2000s survived. This is my measure of success. Moreover, free condoms are infamously everywhere and the South African education syllabus focuses on teaching children about HIV transmission; all this alongside endless television PSAs and government subsidized projects aimed at educating the broader population in this respect.

That said, for Pharma, there has been a decline in new infections. The local pharmaceutical company, Aspen, holds the government ARV tender and the greatest market share in the South African pharmaceutical industry currently.

Opportunity: HIV co-infections present a potential area for growth. The re-emergence of Tuberculosis and certain forms of meningitis present an opportunity for drug development and incremental improvement upon current treatments.


  1. Litigation: Pharma vs. Government

It’s this battle again. Multinational drug companies are constantly in litigation against the SA government; particularly after the introduction of the 1997 Medicines and Related Substances act.

One thing that has to be understood about South Africa is that, unless you are a South African, you may never fully understand South Africa.

We do overkill like nobody else. But for good reason. Our history of discrimination, dehumanization and suppression of our 90% non-white population means that many of our laws and constitutional requirements are very much shaped towards the complete protection of our population; and rightly so.

That said, our department of health has fought tooth and nail to ensure that drugs are available to the South African people cheaply, ethically and affordably.

Drug companies looking to break into / establish growth in the South African drug market have a lot of regulatory hoops to jump through; some of which may not be ideal for their bottom line – which make smaller, more loosely regulated, faster growing African economies more attractive.

Opportunity: South Africa has a huge growing middle and upper class who are privately insured and willing to pay top dollar for the highest standard of medical treatment. Assuming a firm has taken the potential legal climate into account in calculating their risks and opportunities; South Africa can be a highly profitable market.

  1. An excellent Segway: Generics

The market for generic drugs is massive in South Africa, particularly through the public sector. The highest growing pharmaceutical company in South Africa (by a long shot) is Mylan: a multinational firm that specializes in generics in South Africa (good move).

Moreover, since 2014, new drug compounds have reduced as a contributor to growth in the pharma industry. Price and volume changes are currently the two major areas driving growth in the industry. In my view, in the long term, this is not a sustainable model for growth: prices can only increase so much and South Africans have approximately 2 children per woman which indicates linear population growth and caps the extent to which volume can drive revenue.

Opportunity: In terms of market share, there is still room for growth in the generic drug market.


  1. Dual burden of disease

I have discussed this topic at length. South Africa is a perfect example of a nation facing the dual burden of communicable and non-communicable diseases. No, malaria has been fully eradicated. But Tuberculosis is a real and verifiable risk and diabetes and COPD are equally so.

Opportunity: See point 2.

  1. Supply chain: Cutting out the middle men?

The drug supply chain from manufacturer to point of dispensing to patient can be rather confusing. Manufacturers typically dispense their drugs through four major routes: independent couriers, wholesalers, distributors or directly to the three major points of dispensing, pharmacies, hospitals and clincs and grocery stores.

I was in Tel Aviv last December and was surprised that I could not purchase any analgesic drug (Tylenol, Panadol, Nurofen, etc.) at any major grocery store. In all of the countries I have lived in, these over the counter drugs were readily available in grocery stores and I had not realized that this is a relatively unique feature globally.

Opportunity: The primary problem with South Africa’s drug supply chain for the pharmaceutical industry and its consumers is that it becomes expensive and these are costs that may (or may not) be transferred to buyers. Streamlining this is an opportunity in itself; and a sector that manages to form valuable partnerships to successfully linearize this process may be able to drive profits.

  1. Reputation

Whilst South Africa is not the recipient of any foreign aid; a number of its geographical neighbors are. In fact, South Africa is the largest contributor of foreign aid to other African states globally.

Nonetheless, pharma doesn’t have the best reputation down south. One reason for this, rarely covered by the foreign media is the leakage of drugs sent to states meeting the criteria, back into the ‘West’.

An example is an OECD scheme to sell drugs to the 49 poorest states. These drugs are sold at either the cost of production plus 10% or at a price reflecting 80% off the average ex-factory price in OECD member states. This is an excellent aid initiative for those states that benefit from this based on World Bank and IMF standards.

Unfortunately, more recent investigations by Belgian customs authorities uncovered large quantities of GlaxoSmithKline products destined for Africa being sold in the European Union. This doesn’t help the already less than favorable view that many already hold of the pharmaceutical industry, not to the exclusion of Southern Africa.

Have a banging Friday

Cheers, peace and love,


On Booze, Babies and Birth defects:

A brief commentary on Foetal Alcohol Spectrum Disorders


Foetal Alcohol Spectrum Disorders (FASDs) are a group of disorders of global concern. Entirely attributed to prenatal alcohol exposure, affected individuals suffer a lifetime of physical, psychological and social consequences. Foetal Alcohol Syndrome (FAS), has a global prevalence of 2.89 per 1000 live births, with some regions as high as 55.42 per 1000 live births. FASDs are preventable but there seem to be significant gaps in knowledge and practice.

In its 2014 Global status report on Alcohol and Health, the WHO emphasized the importance of strengthening capacity for prevention of FAS and the spectrum of associated disorders. As with many diseases of global concern, a variety of cultural, population and behavioral factors result in certain regions being more profoundly affected than others. FASDs are no exception. Some of the highest prevalence of the disorders globally is seen in South Africa, Canada and Croatia.

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The discussion on FASDs is part of a broader discourse. For the most part, the consequences of the harmful use of alcohol are well understood and documented. Most recent data from a systematic literature review estimates the global prevalence of FAS at 2.89 per 1000 live births. The prevalence of FASDs, however, including other disorders within the spectrum is estimated to be far higher.

The World Health Organization (WHO) estimates that 3.3 million annual deaths occur as a result of the harmful use of alcohol, accounting for 5.9% of preventable deaths worldwide.

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As shown above, after Alcohol use disorders, Foetal Alcohol Syndrome is the most significant cause of death or Disability, measured in Disability Adjusted Life Years (DALYS), attributed to harmful alcohol use. Unlike most health effects and consequences resulting from alcohol consumption, such as Alcohol-use Disorders and liver cirrhosis, FAS does not directly affect the individual. Instead it affects the foetus. Furthermore, unlike almost all other alcohol-attributable diseases, FAS is entirely attributed to alcohol exposure. This relationship between the alcohol consumption of the mother and the adverse, irreversible effects on the infant raises a number of ethical issues in preventing, measuring, interpreting and regulating the factors related to the condition.

DALYs are years of healthy life lost to disease due to disability. One DALY equates to one year of healthy life lost.

Whilst not always considered the most useful measure of morbidity in terms of disability, in conjunction with other indicators, it is generally accepted as a useful metric for understanding health status change and, from a broader perspective, the effectiveness of policy and intervention. In this regard, FASDs are unique. They are not acquired at some point in life as is the case with pancreatitis or accident related injury. In essence, every year of the affected individual’s life is a DALY.

Quality Adjusted Life Years (QALYs), as a metric, are also not immune to criticism. QALYs measure the quality of life provided by healthcare interventions. To its credit, this measure combines both qualitative and quantitative measures of patient’s life quality. In terms of FASDs, however, QALYs are a poor measure. FASD patients require lifelong medical and social intervention to thrive – this is a high level of resource allocation for a condition that can only be monitored, perhaps ameliorated, but never treated.

FASDs are important because they present an important social as well as public health problem in many communities. A major challenge lies in identifying appropriate intervention programs aimed at reducing alcohol intake by pregnant women who are at greatest risk of giving birth to infants with FASD.

In South Africa, the Western and Northern Cape regions have the world’s highest recorded rates of FASDs. Heavy alcoholism within certain groups remains very much commonplace, particularly in the nation’s rural areas. High levels of alcoholism and binge drinking behavior have their centuries old heritage in the dop system, directly translated to mean “tot” or “shot”, whereby Dutch colonists paid farm workers on vineyards entirely or partially in cheap alcohol.

Furthermore, it is reported that on many farms in the Cape provinces of South Africa the use of alcohol as a form of partial remuneration still exists covertly. Current legislation in South Africa prohibits dop, but the legacy of a culture of heavy alcoholism lives on: today some of my beloved country’s rural areas prevalence of FAS is as high as 10.2%.

Foetal Alcohol Syndrome is diagnosed using criteria of facial abnormalities, including smooth philtrum, reduced palpebral fissures and even cleft lip and/or palate. Often infants suffer impaired cognitive development. Those affected by FAS often experience brain dysfunction, mental impairment, psychological disorders and learning disabilities. Furthermore, it often goes undiagnosed for several years. There is no cure for FAS.

FAS brain comparison image blog.png

Foetal Alcohol Spectrum Disorders in particular, distinct from the syndrome, tend to be poorly diagnosed. Particularly where health workers are not very familiar with the condition. Nonetheless, the long-term consequences of FASDs, including pFAS, ARBD and ARND, have a profound impact on the intellectual and social development of the individual.

Although no formal international guidelines on primary, secondary and tertiary prevention of Foetal Alcohol Spectrum Disorders exist, a handful of regional and national studies have investigated prevention methods used in certain areas with an aim to better understand the effectiveness of these varied approaches and how they may be implemented at a larger scale. Indeed, one study showed that merely gaining access to prenatal care resulted in a significant decrease in alcohol use during pregnancy, a luxury to which many women globally, particularly from lower socioeconomic backgrounds, have little or no access

Nonetheless, I would argue that it is the culture of frequent and/or binge drinking that perpetuates prenatal alcohol exposure; perhaps even to a larger degree than ignorance, misinformation or apathy.

Images: whattoexpect; WHO; FASlink; 

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.


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.


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)


  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.


  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.


*All graphs used were taken from, 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.


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.


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.



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!



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.


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


“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


The Basics: Causes of Death

In the past I have written about how non-communicable i.e. non-infectious diseases make up four of the five global causes of mortality. I have also written about how this is, on the whole, a good thing. This article, although based on strong epidemiological data, is heavy laden in opinion.

The objective of this article is to provide a basic outline of the major causes of death. Everyone dies. And on more than a few occasions, I have heard the comments that all, in their own way, suggest that reducing mortality from specific disease causes is merely an exercise in pushing mortality from one disease cause to another; largely based on funding and location.

I wholly disagree with this sentiment.

It is my opinion that a major objective of improving global health is, beyond widening quality healthcare access for all, increasing the number of healthy life years lived by individuals and populations. In this regard, it is preferable to die of a stroke at older age than the next major influenza outbreak within the next five years, or tuberculosis, or pneumonia, or a lower respiratory tract infection. Moreover, the risk factors for most non-communicable diseases are generally modifiable.

The global reduction in childhood illnesses has been huge, although there is still much work to be done, particularly in Sub-Saharan Africa. Case in point: Diarrheal diseases are no longer amongst the top 5 causes of death. (Can you believe that easily treatable, diarrheal diseases were, until recently, amongst the top 5 causes of death?)

I’m glad we no longer live in that world. And whilst cancers, diabetes and cardiovascular diseases are a major force to be reckoned with within the next 15 years of the SDG era, and likely beyond, based on current trends, we are all projected to live longer. And to me, that says ‘improvement’. Even HIV positive individuals, adherently monitored on Antiretroviral Treatment, are living longer: according to some studies, as long or even up to two years longer than average life expectancy.

Most recent estimates place the top 10 global causes of death as follows:

  1. Ischaemic Heart Disease
  2. Stroke
  3. COPD
  4. Lower Respiratory Tract Infections
  5. Trachea, Bronchus and Lung Cancers
  7. Diarrhoeal Diseases
  8. Diabetes Mellitus
  9. Road Injury
  10. Hypertensive Heart Disease

This is important. It is not important to memorize this list, per se, as they are constantly changing. But it is important; as understanding disease profiles and trends is invaluable to understanding the current, global health landscape.

In future articles I discuss the major problem this poses to health systems, economic development and economic stability for individuals and communities, particularly in low and middle-income settings.

For now, have a stellar Thursday!