H5N1

Why arboviruses can be neglected tropical diseases

Thanks to Dr. Peter Hotez for tweeting the link to this important (and prophetic) 2008 article in PLOS Neglected Tropical Diseases: Why Arboviruses Can Be Neglected Tropical Diseases. Excerpt:

Too often, the environmental conditions around urban slums result in perfect larval development sites that will easily support endemic mosquito cycling of disease. Aedes aegypti, the primary vector of many important arboviral diseases, such as yellow fever, dengue, and chikungunya, has been difficult to eradicate and is responsible for the resurgence of many of these diseases. Infections that were once under control, such as yellow fever and Japanese encephalitis, are now capable of returning with a vengeance to poor neighborhoods in both wealthy and impoverished nations. The current outbreaks of yellow fever in Paraguay and Brazil demonstrate our inability to control the resurgence of these arboviral diseases. Practices to escape poverty are also to blame: the spread of yellow fever in Africa and its reemergence in Brazil has been linked to deforestation. 

Access to health care is another important issue for the neglected viral diseases. Although many viral infections are acute in nature and often resolve spontaneously, poor patients come to medical care late in the course of disease, as is often seen with dengue infections. This late presentation leads to worsened disease outcomes than for patients who are financially better off and present sooner. 

Because viral NTDs occur more commonly in those who are poverty-stricken, it can be difficult to decipher all the ways in which the diseases contribute to poverty. Like other NTDs, viral NTDs can lead to debilitating chronic sequelae that impact individual work productivity and family income. RVFV, for example, can lead to permanent visual loss or impairment, which can have a great impact on long-term productivity and quality of life [15],[16]. Importantly, viral NTD outbreaks generally lead to loss of life, family hardship, and distress. Japanese encephalitis is an extreme example, where case fatality rates can be as high as 30%, with one-third of survivors suffering severe neurological sequelae [17]. Because epidemics of arboviruses often receive notice only when they are acute and massive, the public loses sight of ongoing transmission, which has a significant daily impact on the life of people living in endemic countries. 

Too often these diseases are ignored and neglected because they have not yet impacted the lives of those living in affluent areas. Many of these diseases are understudied and go unnoticed until outbreaks affect North Americans or Europeans, as recently displayed in the recent surge of interest in chikungunya after outbreaks on the Indian Ocean islands, a favorite European vacation destination. 

Certain populations within these neglected diseases also go unnoticed, such as the impact chikungunya and dengue have had on neonates and children. The lack of research contributes to our simplified understanding of these infections and our inability to decipher one infection from another. For example, the understudied Mayaro virus may constitute a significant portion of dengue-like illness cases in Latin America. 

As more emphasis is placed on defining the true cost of the NTDs, the real-world problem of concurrent and overlapping infections must be re-evaluated. Although the neglected tropical viral diseases are part of poverty in tropical nations, their full impact is likely not to be determined in isolation, as arboviruses constitute a part of the larger health problem in resource-poor settings. 

More research, more insight, and more discussions regarding these important NTDs and the populations that suffer from them will be necessary to fully define the impact of neglected tropical viruses in the regions where they persist.

Nobel prize winners point the way in battle against diseases of poverty

Via The Guardian: Nobel prize winners point the way in battle against diseases of poverty. Excerpt:

What does it take to bring the fruits of scientific innovation to vulnerable patients in the world’s poorest communities? 

The discoveries recognised by the 2015 Nobel prize for medicine are perfect examples of the journey from test tube to bedside, and tell a fascinating geopolitical story of how effective drugs for neglected diseases are discovered, made, and distributed. Importantly, they show what happens when we work together for patients, not just profits. 

The Nobel recipient Dr Tu Youyou is credited with the discovery of artemisinin, which led to the current arsenal of antimalarial drugs – artemisinin-based combination treatments (ACTs) that have saved millions of lives. 

Similarly, avermectin, the compound discovered by the other two recipients, professors Satoshi Omura and William Campbell, generated the drug ivermectin, an effective treatment against river blindness and lymphatic filariasis, diseases that cause immense suffering and severe disfigurement. 

When these discoveries were made in the 1970s, there was a desperate lack of research and development for diseases that were devastating poor communities in Africa, Asia and Latin America. It was the start of more attention from UN agencies, and the development of numerous organisations to build this capacity. 

Tu was able to get support for her discovery from international and national research institutions, and forged connections with key international pharmaceutical companies. They in turn partnered with new, not-for-profit research foundations to ensure the development of badly needed ACTs that met World Health Organisation recommendations for adults and children. 

Political will eventually coalesced, resulting in a twentyfold increase in malaria funding from 2000 until 2015. To date, artemisinin-based antimalarials have been delivered to more than 600 million people. Treatment for river blindness and lymphatic filiariasis benefited from a similar private-public collaboration. But sadly these important advances were exceptions, particularly for poverty-related diseases where commercial incentives for research are not sustainable. 

On a positive note, a report released on 13 October by the research group Policy Cures at an event organised by the German government in Berlin shows that there are nearly 500 product candidates in the pipeline for neglected diseases, including treatments, diagnostics, and vaccines. Nearly half of these are being developed through public-private “product development partnerships”.

Branswell on one of today's Nobel Prize winners

I've missed Helen Branswell, who recently left The Canadian Press for a gig with Stat, the Boston Globe's new medical site. Here's her first Stat byline, shared with Eric Bloodman: Nobel winner: ‘Is there some way I can verify this?' Excerpt:

When biologist William Campbell answered the phone before dawn on Monday, he was startled to hear a reporter telling him he had just won the Nobel Prize. In his confusion, he ended the call abruptly. 

A moment later, Campbell called the reporter back. “I said, ‘It’s not that I mistrust you, but is there some way that I can verify this?’” Campbell recounted in an interview with Stat at his home in a retirement community. 

The reporter directed him to the Nobel website, where Campbell found his verification: He was a co-winner of the 2015 prize for physiology or medicine. Campbell, 85, and biochemist Satoshi Omura of Japan share half the prize for their work to develop ivermectin, a drug that combats parasites which cause two debilitating diseases, river blindness and lymphatic filariasis. In severe cases, the latter can develop into the condition elephantiasis, which causes swelling of the limbs.  

The other half of the award was won by Chinese scientist Youyou Tu, who scoured ancient Chinese texts looking for a traditional remedy for malaria. She focused her efforts on a plant called sweet wormwood, or Artemisia annua. The result: the drug artemisinin, a first-line therapy and a lifesaver. 

In both cases, the award honors work that was done decades ago. In the intervening time, the two drugs have benefited hundreds of millions of people. 

“These three scientists have had a massive positive impact on global health. This was a great choice by the Nobel Committee,” said Dr. Christopher V. Plowe, president of the American Society of Tropical Medicine and Hygiene. 

In the case of ivermectin, the discovery is only half of an incredible story. When Campbell realized his team at Merck & Co., Inc. – his longtime employer – had a drug that could treat infections with debilitating parasites, he and others also quickly realized that the people who needed the drug could not afford to pay for it. 

He and his boss talked to Dr. Roy Vagelos, then the CEO of Merck, who made the bold decision to donate the drug — as much as was needed for as long as was needed — to groups working to control river blindness. Later, the free supplies were extended to combat filariasis. 

“It was a gutsy move. It’s a very difficult thing to give a drug away,” said Campbell. 

He said at the time there was concern that other drug companies might stop working on therapies for diseases that afflict the world’s poor if they felt they, too, would be expected to give them away. 

It did create a precedent, but not the one Merck feared, said Craig Withers, acting vice-president of health programs at the Atlanta-based Carter Center, which has been instrumental in the work to fight river blindness, formally called onchocerciasis, and filariasis. 

In fact, Withers said, the Merck decision gave birth to the effort to combat what are known as neglected tropical diseases.

WHO strengthens focus on water, sanitation and hygiene to accelerate elimination of neglected tropical diseases

A news release from WHO: WHO strengthens focus on water, sanitation and hygiene to accelerate elimination of neglected tropical diseases. Excerpt:

The World Health Organization (WHO) today unveiled a global plan to better integrate water, sanitation and hygiene (WASH) services with four other public health interventions to accelerate progress in eliminating and eradicating neglected tropical diseases (NTDs) by 2020. 

“Millions suffer from devastating WASH-related neglected tropical diseases – such as soil-transmitted helminthiasis, guinea-worm disease, trachoma and schistosomiasis – all of which affect mainly children,” said Dr Maria Neira, WHO Director for Public Health, Environmental and Social Determinants of Health. 

“Solutions exist, such as access to safe water, managing human excreta, improving hygiene, and enhancing targeted environmental management. Such improvements not only lead to improved health, but also reduce poverty.” 

Targeted water and sanitation interventions are expected to bolster ongoing efforts in tackling 16 out of the 17 NTDs, which affect more than 1 billion of the world’s poorest and most vulnerable populations. 

A recent report showed that in 2015 more than 660 million people did not have access to improved water sources. The WHO/UNICEF Joint Monitoring Programme for Water Supply and Sanitation report also showed that almost 2.5 billion people lacked access to improved sanitation. Open defecation and lack of hygiene are also an important risk factors for the transmission of many NTDs. Over half a million lives are lost each year as a result of NTDs. 

"Joint planning, resourcing and delivery of WASH interventions are key to eliminating neglected tropical diseases and in achieving many public health and human development goals" said Dr Dirk Engels, Director of the Department of Control of Neglected Tropical Diseases. 

"The benefits are enormous - from alleviation of suffering through improved outcomes to healthier, wealthier and happier families, communities and nations."

Good and bad news about Ebola

Thanks to Greg Folkers for sending the link to this report in PLOS Neglected Tropical Diseases: Good and Bad News about Ebola. Excerpt:

The simple fact is that the world has become very small in recent decades. Connectivity via rapid travel on local, regional, and global scales makes epidemic spread massively efficient [6]. This global linkage means that a person almost anywhere in the world can be in the US or Europe within 48 hours, and thus that no disease outbreak anywhere can be considered as unlinked to the US or Europe, at least potentially [7]. 

The implications for disease control and prevention, and particularly for taking care of “American” interests in that regard, are immense—the number and variety of diseases that may come into play are considerable. 

In this regard, the hemispheric or global spread of a series of diseases comes into a different light: Severe Acute Respiratory Syndrome (SARS), West Nile virus, and chikungunya all are examples [8]. Note that each of these diseases was unknown to or ignored entirely by the pharmaceutical industry, and slightly less completely by the research funding and research communities. 

Only when they spread into the US and European realm did these diseases see intense research attention—the arrival of West Nile virus in North America [9] is an excellent example: a total of 278 publications accumulated from 1942 through 1998, but yearly numbers of publications averaged 420 once the virus arrived (Fig. 1). Ebola is already following a similar trajectory after this (tragic) banner year of 2014, as can be appreciated from the inset in Fig. 1. 

So what hope is there for the numerous neglected diseases, particularly in the Tropics? Many of them never get identified and described by scientists (see, e.g., the case of Lujo virus [10]) because they are not spectacular in their effects or because they do not occur in areas with good medical diagnostic facilities; those that are known are neglected in the sense that no pharmaceutical company would invest in a cure, a vaccine, or even intense research on them. Such neglected diseases include Chagas disease, human African trypanosomiasis, the leishmaniases, echinococcosis, lymphatic filariasis, onchocerciasis, schistosomiasis, Buruli ulcer, and many others [11]. 

Although research on neglected tropical diseases is supported by several US government programs (e.g., President's Malaria Initiative, President's Emergency Plan for AIDS Relief, and USAID’s Neglected Tropical Disease Program), as well as by several international and nongovernmental efforts (e.g., Global Fund to Fight AIDS, Tuberculosis and Malaria; Bill & Melinda Gates Foundation; Children’s Investment Fund Foundation; World Bank Group), clearly, the challenge is costlier than present resources can manage [12]. 

If the present situation with Ebola is to offer any lessons, they are that the only hope for serious investment in reducing the incidence and impact of such diseases is via spread to developed countries. Once such spread occurs, research and pharmaceutical investment will most likely follow. Ebola is a positive example, and clearly Ebola research will enter a new phase of progress, innovation, funding, production of key pharmaceuticals, and improved care, hopefully for all who might be infected by this virus. 

In effect, what Ebola did was to cross the line between being a “neglected tropical disease” and being an “emerging infection.” The former set of diseases collectively exert an enormous burden in the developing world that may be constant or episodic, but are rather ubiquitous in those regions, affecting the affluent only when they venture into those regions [13,14]. The latter, on the other hand, are much less predictable, but garner more immediate attention on the world scene, precisely because they may affect affluent countries. 

How many other neglected diseases must await this process of spread to affluent regions and infection of affluent people, making the transition from neglected tropical disease to emerging infection, before they also will see investment and innovation?

WHO urges governments to increase investment to tackle neglected tropical diseases

A news release from WHO: WHO urges governments to increase investment to tackle neglected tropical diseases. Excerpt:

WHO urges affected countries to scale up their investment in tackling 17 neglected tropical diseases in order to improve the health and well-being of more than 1.5 billion people. This investment would represent as little as 0.1% of current domestic expenditure on health in affected low- and middle-income countries for the period 2015-2030.  

Neglected tropical diseases cause blindness, disfigurement, permanent disability and death, particularly among the poor. WHO’s new report, "Investing to overcome the impact of neglected tropical diseases", outlines an investment case and essential package of interventions for these diseases. 

“Increased investments by national governments can alleviate human misery, distribute economic gains more evenly and free masses of people long trapped in poverty,” says WHO Director-General Dr Margaret Chan. 

Progress  

The report highlights progress made in recent years, largely attributed to a scale-up of control interventions in reaching the poorest. For example, in 2012 alone, more than 800 million people were treated for at least one neglected tropical disease. In 2014 there were just 126 cases reported of Dracunculiasis (guinea-worm disease), compared to almost 1800 in 2010 and 3.5 million in the mid-1980s. Eradication of this disease is achievable with continued effort and investment. 

Need for increased domestic investment targets 

The report sets specific investment targets for many of the 17 diseases. It stresses that countries must make firm and sustainable budgetary commitments if they are to meet WHO targets and accelerate progress. 

The investments 

• An annual investment of US$ 2.9 billion until 2020 (including vector control), is required to reach targets set in 2012 in the WHO Roadmap for 2015-2020. 

• For the following 10 years (2021-2030), investment requirements will drop to US$ 1.6 billion per year. Annual investments will continue to decrease as diseases are reduced or eliminated. 

• This adds up to a total investment of US$ 34 billion (over 16 years) and excludes cost of donated medicines and other in-kind contributions. 

The impacts 

• By 2017, the number of people receiving preventive treatment for at least one of the diseases should reach 1.5 billion. As diseases are reduced or eliminated, the number of people needing and receiving treatment will obviously fall. Early detection of some neglected tropical diseases will allow more children to continue school and adults to work while reducing the costs associated with treating more advanced forms of these diseases. 

• Moving towards universal health coverage will ensure that all people have access to preventive and curative health services for neglected tropical diseases without the risk of financial hardship when paying for them.

Ebola is in America – and, finally, within range of Big Pharma

Via The Observer: Ebola is in America – and, finally, within range of Big Pharma. Excerpt:

Research funding for neglected tropical diseases rose 3% to $3.2bn in 2012 after years of decline, according to a survey funded by the Gates foundation. But pharmaceuticals firms contributed just $527m – a fraction of total spending on research and development of $130bn. Most of the money spent on tropical diseases – two-thirds of it – comes from governments. 

A study published in The Lancet last year showed that of the 336 new drugs developed between 2000 and 2011, only four were for neglected diseases (three for malaria and one for diarrhoeal diseases), and of 150,000 trials registered in late 2011, only 1% tackled NTDs. 

Ebola could change all that. Deutsche Bank analyst Mark Clark says: "Ebola could be the issue that sends the whole thing snowballing. You are going to get more industry engagement. The signs were already positive after the London Declaration on NTDs in 2012." 

Jacobson reckons the 2020 goals are "ambitious on all fronts" but "each one is attainable", even though a funding gap of $1.5bn remains. "Unfortunately, it's always a good thing for a disease to make it to an industrialised country," she says. "A lot of tropical diseases have been invisible to the world." 

A progress report from signatories of the London declaration earlier this year highlighted early successes: Colombia became the first country to verify the elimination of river blindness (followed by Ecuador); Nigeria, Niger and Ivory Coast were certified as free of Guinea worm; and Morocco has been declared clear of blinding trachoma. 

Within the industry, GlaxoSmithKline, Britain's biggest drugmaker, and France's Sanofi are investing the most, each putting more than $100m a year into tropical disease research, according to Deutsche Bank. They are followed by Switzerland's Novartis, which plays a key role in the supply of antimalarial drugs in Africa, its Swiss rival Roche and Germany's Bayer. 

By contrast, most US pharmaceuticals firms regard tropical diseases as a philanthropic venture and restrict themselves to donating off-patent drugs such as anti-worm tablets, Clark says. 

He added: "To the extent that these diseases are starting to appear in the US, this will put the issue much more firmly on [US companies'] radar."

What is killing young Central American men?

Via PLOS Speaking of Medicine blog, a fascinating post: Tropical Medicine Mystery: Something is Killing Young Men in Central America. Excerpt:

Over the last decade drug trafficking and violence have taken the lives of thousands of people, most of them young men, in Guatemala, Honduras, and elsewhere in Central America.  Far less known is Central America’s hidden killer disease that has recently been named Mesoamerican nephropathy.  

Mesoamerican nephropathy appears to be an emerging form of chronic kidney disease of unknown etiology that disproportionately strikes young male agricultural workers primarily in the Pacific coastal regions of El Salvador and Nicaragua, but also in Guatemala and Costa Rica.  

According to Correa-Rotter et al the syndrome was first described in 2002 as a form of advanced chronic kidney disease at the Rosales Hospital, a referral hospital in the capital of El Salvador, which developed without the usual chronic risk factors such as diabetes and hypertension.  Among its most common features, Mesoamerican nephropathy typically presents as a progressive tubulointerstitial form of renal disease and failure with no or low grade proteinuria.  

The histopathology findings from renal biopsies are unique and different from other causes of renal disease.  It most commonly affects young men working in sugarcane plantations along the lowland Pacific Coast of Central America. Because this part of Central America is a resource poor area, those affected often die prematurely due to inadequate access to renal dialysis. 

Some investigators believe that Mesoamerican nephropathy is now the leading killer of young male sugarcane workers in Nicaragua and possibly El Salvador. 

A number of theories have been advanced to explain the etiology of Mesoamerican nephropathy.  They include environmental exposures to various agrochemicals, heavy metals, and mycotoxins, as well as recurrent dehydration in the setting of Central America’s hot coastal climate.  

We are proponents of exploring potential infectious causes, especially zoonotic neglected tropical diseases from rodents that notoriously infest sugar cane plantations. Lead candidate infections might include leptospirosis, hantavirus, and Mansonella filarial infections, which are well known in Central and South America.  

Still another possibility is West Nile virus infection shown recently by one of us (KOM) and her colleagues to produce a chronic and progressive renal disease leading to kidney failure. 

WNV infection may now represent a leading cause of renal disease in Texas, and it is conceivable that this mosquito-transmitted disease may have emerged on Central America’s Pacific Coast.

Declaration of the Global Chagas Disease Coalition

Via the PLOS blog Speaking of Medicine: Declaration of the Global Chagas Disease Coalition. Click through for the full statement and many links. Excerpt:

Chagas disease is a silent killer. Throughout the Americas, an estimated 8-10 million people, most of whom are predominantly poor and marginalized, are infected by the deadly parasite causing Chagas disease, Trypanosoma cruzi. Children are particularly affected. With globalization, the disease is increasingly found in the US, Europe, Australia, and Japan. The US is now the seventh most affected nation worldwide. 

Tens of thousands of patients die each year from Chagas disease. About 30% of chronically infected individuals will develop heart complications with high probability of death. Less than 0.2% receive treatment today (DNDi, unpublished data). New problems are emerging notably with mother-to-child transmission, which could become the new face of Chagas disease. 

Chagas disease is a hidden public health crisis needing increased and urgent attention. 

As researchers, clinicians, patients, funders, civil society, and public health practitioners engaged in research and development (R&D) and implementation of treatment and prevention programs, we have decided to join forces to create a coalition aimed at changing the future of Chagas disease. 

The World Health Organization (WHO) and Pan American Health Organization (PAHO) have developed strategic plans supporting national control programs in endemic countries. Other recent initiatives such as the 2012 Uniting to Combat Neglected Tropical Diseases ‘London Declaration’ have included Chagas disease as a priority. 

This context represents an unprecedented opportunity to help define a patient-centered agenda that boosts access to existing health tools and treatments, supports integrated vector-control prevention measures, and expands global efforts to stimulate innovation for new and improved tools to control Chagas disease.

Fighting polio versus all the other diseases

Via The Independent in the UK, a thoughtful editorial: Polio is going – but not yet gone. Excerpt:

When a disease achieves “celebrity status” – garnering attention and resources – there is bound to be resentment among those working on other conditions that have been overlooked. 

HIV/Aids came to global notice in the 1980s and 1990s and sucked in funds on a scale hitherto undreamt of in the developing world. Meanwhile, malaria, tuberculosis and, the biggest child killer of all, diarrhoeal disease were neglected, opening up sharp divisions in the aid world.

Today the world is facing a similar situation with polio. Thanks to eradication efforts over the past 25 years, the total of cases worldwide has been reduced by 99 per cent, to just 222 last year. For the generation that remembers the outbreaks in 1950s Britain, Europe and the US, when thousands of children died or were left paralysed and panic gripped parents, that is an astonishing achievement.

But the work is not cheap  – $9bn has been spent so far – with an estimated $5.5bn required to root out the last couple of hundred cases, equivalent to $25m for each case. Health workers running routine immunisation programmes for measles, diphtheria and other lethal diseases complain that all the focus has been on polio.

Local people protest, during the frequent polio immunisation days, telling health workers bitterly: “You only give us polio drops, but we have so many other problems.”

Of course, those last cases won't be "rooted out." They'll just be identified, and the victims will get very little aid. The money is going to prevent hundreds of thousands, if not millions, of future cases. The vast majority of those saved will lead healthier and more productive lives—a very good return on $5.5 billion or whatever it takes.

But the editorial has a valid point: We tend to play favourites with diseases, and to focus our efforts on the favourites. When we really can eradicate a disease from the face of the earth, it's worth it. But the neglected diseases, the unglamorous diseases, the diseases we personally are unlikely to contract—those are the diseases we should planning to battle as well.