Archive for August, 2013

Life of an epidemic: Australian dengue

mosquitoes everywhere

It is always a bad sign when crowds gather. On the morning of Wednesday March 21 in the year 1900, a crowd began to gather in Sydney. A thousand people had gathered outside the offices of the Board of Health in Macquarie Street. They had gathered because bubonic plague had broken out. People had already started to die from the Black Death. Panic was the only course of action.

The Government had stockpiled Haffkine’s serum (named after the Russian bacteriologist that developed it in a makeshift laboratory in a corridor of Grant Medical College) — a new plague vaccine, and had used it to inoculate front‐line health workers, new plague victims and anyone who might have come in contact with them. The panic was because the Sydney papers had been campaigning for a public vaccination program.

When the Board of Health finally opened its doors that morning, the crowd overran the place. In the melee property was damaged. Not much happened to inoculate people that day. In the end, the public inoculation campaign was abandoned. It would be another two decades before Australia was free from plague.

Australia has a long history of epidemic and pandemic encounters. Smallpox, polio, scarlet fever in 1830 that lasted for half a century, intermittent and regular bouts of influenza, and encephalitis lethargica.

Like it or not we are in the midst of a number of epidemics, not just in Australia. There are the fast moving ones that happen with many newspaper column inches like SARS and MERS — whipping up a frenzy of unpredictability. There are those that have become a part of the conversation like HIV/AIDS. And there are those that go under-reported like Dengue fever.

dengue virus

dengue virus

Explosive dengue

From November 2008 to May 2009 Cairns, Queensland was struck by an explosive epidemic of dengue virus (DENV-3). One that exceeded the capacity of the highly skilled dengue control teams to control it.

Australia is no stranger to outbreaks of this nature. A dengue outbreak had already occurred previously — in 1992. One of the consequences of that large multi-city outbreak was the development of the Dengue Fever Management Plan (DFMP) by Queensland Health in 1994.

Between 1995 and 2012, there were 42 outbreaks comprising of 3,086 confirmed dengue cases and three deaths; the majority (37 outbreaks and 2,364 cases) have occurred since 2000.

Piecing together the fragments of an epidemic

The weather can predict disease, and create the perfect set of contitions for an epidemic to take hold. The climate in the months leading up to the outbreak of the epidemic was apt for the spread of the vector — the Aedes aegypti mosquito. The Cairns dry season, from May to November, customarily has low rainfall. In 2008, rainfall at the time was significantly more than usual, with heavy rains towards the tail end of September.

The heavier than usual rain was thought to have hatched mosquito eggs leading to the rapid escalation of mosquito numbers, serving as a primer for the outbreak that was yet to come.

For this epidemic to take hold and spread, it required a some-what perfect sequence of events. Unseasonably warm weather, with daily mean temperatures exceeding 30°C, occurred in late November and would have shortened the incubation period of the virus and enhanced transmission.

Researchers analysed case movements early in the outbreak and found that the total incubation period was as low as 9 days. They replicated and confirmed it in a lab setting and it took just 5 days.

27 days passed without the Queensland Health authority knowing about the outbreak. This allowed the virus to amplify and spread unchecked through its first month in Australia. Human-mediated dispersal were the words they used to describe it. The seasonal movement of people around that time most likely also enhanced the spread of the virus.

In all the virus had an unusually rapid transmission cycle that allowed it outpace control efforts.

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Patient Zero

Sometime before the 3rd November 2008, a flight landed in Cairns. The flight brought back with it, among many other things, a passenger who had visited Kalimantan in Indonesia the previous month. Two days after the flight landed the passenger was to fall sick. It wasn’t yet clear it was dengue. Later it became clear that the passenger was the index case — importing the virus and initiating the outbreak. There had been no reported cases of DENV-3 in Cairns since an outbreak in 1998.

Researchers discovered that the first group of cases in the epidemic all came from within 200 metres of the index case. By day 17 of the outbreak there were already 6 local cases.

By the following spring, the rate of infection had dropped dramatically. Despite health services playing catch-up for most of the epidemic, ending the outbreak was a tour de force. The outbreak received widespread media attention — motivating a well-informed public to remove any water-holding containers that could act as a breeding ground for mosquitoes.

The public health effort was cyclopean. State emergency services went door to door, delivering information kits and cans of pyrethroid surface spray to residents in suburbs at risk. A SMS texting service sent messages to mobile phones warning residents of active virus transmission within their residential area. Man power was mobilised. After declaration of the epidemic in January 2009, additional vector control personnel were employed.

There was hardly any suburb in Cairns that had not reported cases of dengue, and had not been subject to vector control by April of the following year.

In the end, the outbreak caused 931 confirmed cases and one single death on 4 March 2009. And cost Queensland Health somewhere in the region of 3 million australian dollars.

What would eventually become evident was that even with what seemed like a highly professional contingency system in place to deal with an epidemic such as this — this time round, the disease got the better of them. This time round the epidemic was different. Different in the way it moved through the population.

“The apparent speed of transmission and its rapid geographic spread overwhelmed what had been a successful, organized first world dengue control program”

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Public Health in the Age of Austerity

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“Care of the public health is the first duty of the statesman”

In 1932, the American Public Health Association, publishing in the American Journal of Public Health, called on their government not to forget about them. The consequences, they claimed, would be dire. They described it as a present state of emergency.

At the time, they felt that the situation in the United States, during the heights of the depression, had got to such a state, that it warranted immediate action. They sought to call attention to the inherent dangers involved in slashing public health budgets, reducing personnel, and limiting health programmes. They cited preventive campaigns against diphtheria and typhoid fever that would suffer.

It was the time of the Great Depression. The decade that immediately preceded it — the roaring 20s — saw runaway economic growth providing prosperity for all. The end of the decade and the 30s, however, began to stagnate, signposted by the stock market crash of October 1929. The collapse of Wall Street was followed by a steep decline in economic activity — gross domestic product was counted in negative numbers, and unemployment was at an all-time high — reaching a historical maximum of 22.9% in the US in 1932.

The idea has always been that an economic downturn also led to a downturn in public health. Historically, there has been no greater spur of health and wellbeing than a prosperous nation. The wealthier the nation then the more it spent on the health of its citizens. It may seem counter-intuitive to think that the era of the Great Depression was a time that actually saw declining death rates in Europe and in the US. During the Great Depression, life expectancy rose significantly from 57.1 years of age in 1929 to 63.3 years in 1933. Rates of infant mortality declined during the 1920s and 1930s. Within those two decades the only years that saw an increase in mortality were years that coincided with short bursts of strong economic growth. Famously, the most notable cause of death during this period was suicide. Death by suicide peaked with unemployment.

“It is futile to quote the great men of the past, statesmen, as well as scientists, to prove what health means to any nation.”

This is a recurring theme over the course of history. One that we don’t pay much attention to. As the health of a nation gets better we tend to forget of the vigilance and strife that was needed the first time round. Eventually, health is a given. So much so that it is only when a scandal hits that we see how much we take it for granted. Comparing developed against developing nations is where we see the greatest contrast. Vaccinations are part and parcel of a newborn life in some countries. Children cannot go to school without it. This seamless integration of public health into everyday life does not exist everywhere.

Fast forward to today’s economic recession, where the US is witnessing a decline in its public health laboratories. These public health laboratories provide testing for drinking-water testing, sexually transmitted diseases, HIV screening, blood lead screening, substance abuse monitoring to support treatment programs, and detection of bioterrorism agents in environmental samples and isolates from humans.

A decline that is due in part to deficient state and local tax revenues resulting from loss of taxpayer jobs and income tax revenues and loss of homeowner and business property tax payments due to foreclosure. Decreased funding has resulted in loss of public health jobs due to layoffs and attrition, program cuts and reductions.

When the University of Michigan’s Center of Excellence in Public Health Workforce Studies, together with the Association of Public Health Laboratories, assessed the workforce and program capacity in US public health laboratories back in 2011; they found that almost half of laboratories anticipated that more than 15% of their workforce would retire, resign, or be released within 5 years.

In Michigan, they lost more than 300 years’ worth of employee experience over the course of 3 months. In attempts to control budgets, state and local governments incentivized retirement. Resulting in loss of the most experienced, expert employees and additional burden of work for remaining employees.

Cuts and straitened times seems part and parcel of today’s economic downturn. Little discussion takes place on how this will ultimately shape the health and wellbeing of nations. Demand for services from an ageing population and increased costs created by new clinical  and pharmacological technologies, will all put upward pressure on health spending. This is the case in the US and in the UK.

Some see it as an opportunity, however. An opportunity to finally bring two opposing forces together — public health and medicine. Writing in the New England Journal of Medicine, researchers argue for simple population-based approaches to address fundamental health problems. Obesity tackled at the population level rather than at the individual level. A focus on the population as a whole rather than simple service delivery of intervention medicine.

“Perhaps paradoxically, the current push for austerity could bring together clinical medicine and public health in unprecedented, mutually beneficial ways that could improve population health and reduce spending”

The idea is simple and looks to do more with less. Such is life in the age of austerity.

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Australia’s evolving drug landscape

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This year we saw Australia put into force a new patent law. An intellectual property system that was Australia’s most comprehensive in over two decades. It came into effect on 15 April 2013 and no one knew exactly what to expect from it.

We have seen with cases like India, how one country’s patent laws can send ripples and disrupt the entire system. And, in the case of Thailand, how a country can take matters into its own hands to enact a public good.

It really all centres around compulsory licensing. A compulsory license, in simple legalese, is the use of a patented innovation that has been licensed by a state without the permission of the patent title holder. This started over a decade ago, when the World Trade Organization adopted the “Declaration on the TRIPS Agreement and Public Health” at its 4th Ministerial Conference in Doha. At the time, many anticipated that this would lead nations to more frequently claim compulsory licenses for pharmaceutical products.

The TRIPS Agreement allows governments to license the use of patented inventions to someone else without the consent of the patent owner. It does not and should not prevent nations from taking measures to protect public health — that was the way it was billed and sold. In dealing with public health epidemics, such as HIV/AIDS, tuberculosis and malaria, countries such as Brazil, India, Thailand, Indonesia and Ecuador have used compulsory licensing to reduce the prices of pharmaceutical drugs for their citizens. What has been seen is a significant spike in use of compulsory licensing in years since Doha.

So where does Australia sit in this spectrum?

Last month, the Australian Parliament was debating a bill on patent law and public health called the Intellectual Property Laws Amendment Bill 2013. It is said that the legislation gives Australian governments greater powers to exploit patents without authorisation from the patent owner via stronger provisions for Crown use and compulsory licensing. Perhaps something more along the lines of what Thailand enacted in 2007. Thailand played the global system to their advantage, exploiting a clause in the 1995 World Trade Organisation agreement on intellectual property that gives governments a large amount of freedom to bypass patents on drugs if they face any kind of health crisis.

Begging the question; in this day and age — aren’t we always under a health crisis? Whether it be from the scourge of tropical diseases in developing countries or the rise of affluent afflictions like heart disease and cancer.

Recently, the Sydney Morning Herald reported that the bill was likely to pass. Going further to state that this would allow Australia to export generic versions of patented drugs to developing countries to tackle outbreaks of diseases such as malaria, HIV and TB. Perhaps becoming the second “pharmacy of the developing world” alongside India. It seems the right balance was achieved between helping people in poor countries and safeguarding intellectual property.

There is another side to outwardly-looking medicine laws in a country. And that is the inwardly looking.

Australia has a drug subsidy scheme, that provides subsidised prescription drugs to residents of Australia — ensuring that all Australians have affordable and reliable access to a wide range of necessary medicines. The scheme has come under some recent controversy.

In 2011 and in 2012, the number of new medicines placed on the nation’s drug subsidy scheme was the lowest seen in two decades. This drop, despite no reduction in new therapies being proposed but just because of a higher rate of rejection by the advisory committee in charge of approving subsidies.

The drop brings up the question of where does this leave patients? With the scheme put in place to ensure that even the poorest of patients can get life-saving medicines the whole “Access to Medicines” debate is revisited. In this case, a slightly shifted one than the usual Big Pharma profit story. Numerous examples exist where the inability to get drugs directly influences patients.

In the ever-increasingly complicated world of drugs, medicine, and economics… the right to a healthy well-being is also being tested.

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Curious case of armadillo leprosy

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Texans love all things armadillo. It is the state animal and Texas has become somewhat of a haven for hunting the small creature. In Louisiana and Texas, people hunt, skin and eat armadillos. Nothing exemplifies this all-things-armadillo attitude quite like the fact that barbecued armadillo and armadillo chili are popular delicacies in Texas. During the Great Depression Texans went as far as to stock their pantries with armadillos.

Every year, a significant number of people in southern United States walk into emergency rooms presenting with lesions of unknown origin. The lesions are quite clearly as a result of leprosy, but with some patients showing no history of foreign exposure (leprosy is not endemic to the United States) how they ended up with leprosy had always been somewhat of a mystery. Leprosy is rare in the United States, with only about 150 new cases reported each year — the majority of affected people lived or worked abroad in leprosy-endemic sub-tropical regions and may have acquired their disease there.

Leprosy is not highly infectious — caused by the slow-growing bacillus, Mycobacterium leprae, and transmitted via droplets from the nose and mouth of infected and untreated patients. It can cause nerve damage, leading to muscle weakness and atrophy, and permanent disabilities when left untreated.

It was in a lab in Baton Rouge, Louisiana that the case was first confirmed. Whole-genome resequencing of the leprosy bacteria from one wild armadillo and three US patients with leprosy revealed that the infective strains were identical. Infected armadillos had been reported across the southern United States, in Alabama, Arkansas, Louisiana, Mississippi, Texas, and Mexico, with several case reports have suggested that armadillos may be a source of the bacteria. The building body of evidence that these small animals act as a reservoir for the disease.

Even though leprosy is exceptionally rare in the United States, it seems exposure to armadillos in southern states is quite common. Authors publishing in the New England Journal of Medicine show that a single predominant strain is involved in most human and armadillo infections. Transmission is relatively easy, either direct or indirect, involving fomites. Although in this case the authors suppose it occurs most frequently through long-term direct contact with an infected host as the bacteria doesn’t last for long out in the environment.

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Historically, leprosy had been hard to study. Very few animal models provided an adequate host for the disease. It grows vigorously in one animal — the armadillo, a fact discovered only in the 1970s at another federal laboratory in Baton Rouge. The nine-banded armadillo, Dasypus novemcinctus, is the only species of armadillo that occurs in North America, wondering north from Central America sometime during the early Pleistocene.

There was a time, before sophisticated experimental techniques, when the bacteria for leprosy couldn’t be cultured. Research, especially research that deals with combating infectious diseases relies heavily on being able to culture the infectious agent in a controlled environment. They tried experimentally to transmit the bacteria to other animals such as mice — but failed. Not being able to produce enough bacteria to be truly useful is always a setback for research. Add that to the fact that mice don’t live very long and human leprosy can be over the course of two decades.

Armadillo leprosy closely resembles the infection in humans — the lesions in its nerves was evidence of the armadillo as a suitable model animal.

Today, it is estimated that a third of the leprosy cases that arise each year in the United States almost certainly result from contact, in one form or another, with infected armadillos. Interspecies transfer of the disease is uncommon and inefficient, but within the armadillo species transmission is efficient.

What is becoming more and more evident is a complex problem — the ever increasing, incrementally advancing scourge of certain tropical diseases towards previously virgin areas, together with the fact that doctors have never seen these sorts of exotic diseases on a regular basis means there is frequent misdiagnosis. And as an estimated 70 percent of new emerging infectious diseases were known to have animal origins, perhaps it’s time to reflect and reframe the question.

The microbe that causes leprosy is a fragile one. It does not grow in laboratory petri dishes, and survives only a week or two in moist soils. Its presence in armadillos predates the fact we use it as a disease model. Ironically, armadillos would have acquired it from humans sometime in the last 400 to 500 years — sometime after colonization of the New World. Now they’re giving it back…

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Middle East Coronavirus

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Since the summer of last year, the perennial talk of epidemics and pandemics has focused on a novel coronavirus. A virus that belongs to a diverse group of that affects many animal species — from bats to humans. At the time the public health risks were unknown. How many could eventually possibly become infected or die? How does the virus spread? Is Human to human transmission possible?

During the summer of 2012, in Jeddah, Saudi Arabia, the unknown coronavirus was isolated from the sputum of a patient with acute pneumonia and renal failure. To date, 55 laboratory-confirmed cases have been reported to the World Health Organisation. 31 individuals with laboratory-confirmed infection have died. Directly or indirectly most cases have been linked to four countries in the middle east; Saudi Arabia, Qatar, Jordan, and the United Arab Emirates. Now known as the Middle East Respiratory Syndrome Coronavirus (MERS-CoV), the exact scale and full parameters of a disease that the world is still understanding are slowly coming to the forefront.

Roughly two months ago a 73 year old man from Abu Dhabi died in a Munich hospital. He died on the 18th day of his infection of septic shock from the coronavirus infection he was suffering from. It is this patient, who was admitted to the Klinikum Schwabing in Munich in March, that is the subject of newly published research revealing more about the virus’ clinical features. Publishing in the Lancet, the research highlights the need for a therapeutic approach and that more data and research are needed. Little comprehensive clinical data on the new virus exists. In all, cases have been documented in Arabian Peninsula, Tunisia, Morocco, France, Italy, Germany, and the UK. Although one case in France turned out to be a false positive. Across all the documented and reported cases this is only the fifth patient for whom the virus’s progression and characteristics have been described in a medical journal.

A question early on had always been, is this the next SARS? In the spring and summer of 2003, the global outbreak of severe acute respiratory syndrome (SARS) caused more than 8000 probable or confirmed cases and 774 deaths in 25 countries across five continents. A health scare of pandemic proportions. And that is the new state of fear with every new mysterious infection. The new coronavirus (MERS-CoV) is one which Dr Margaret Chan, the Director General of the WHO, described as “my greatest concern right now.”

It seems the initial moniker of “novel” coronavirus was apt. The Lancet study shows key differences. Namely, between how the new virus circulates in the body compared with the SARS virus. This comparison to SARS, somewhat due to its initial similarities, but also because of how little we know about MERS-CoV.

“Laboratory data are crucial for diagnostic recommendations to make projections about prognosis, and to estimate infection risks. Without quantitative laboratory data from well documented cases of MERS-CoV infection, most considerations had been made on the basis of an assumed analogy to severe acute respiratory syndrome.”

This coming after recent pleas by the WHO for those working on the virus to share more information. Saudi Arabia has recently said that the development of diagnostic tests have been delayed by patent rights.

Despite the complications inherent in modern medicine and research into emerging infectious diseases, one thing is clear — only analysis of a large number of patients can be fruitful enough to really chart this virus and its disease patterns.

These types of advancements only really come from patient information. And only really comes when a patient finally succumbs to their infection.

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What had I twaught…


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