Archive for May, 2012

London Olympics and the effect of mass gatherings…

59 Days to go.

Simply put, for those that care about the London Olympics — the excitement is mounting. With 26 sports across 44 venues, 10,500 athletes and millions of spectators, it’s going to be a busy summer. From Box-hill to Coventry, and all across London the preparations are almost over and it’s almost time for the curtains to go up. Behind the scenes  a workforce of around 200,000 people are being amassed — comprising of around 6,000 paid full-time and temporary employees, up to 70,000 volunteers and around 100,000 contractors. A small army. Add to this another small army of reporters and media that will cover the games from every angle. The American broadcaster NBC will be sending a team of around 2,800 to London. The BBC will deliver a record 2,500 hours of live action from the games, including 26 channels dedicated to each sport. An Olympic staff (in more ways than one) that actually outnumbers Team GB itself by a considerable margin.

As Londoners, nonplussed about it all, make a quiet exit for a few weeks, the city and those unlucky enough to be caught in it, are going to be overrun with tourists, sightseers, and everyone else.

The amount of column inches dedicated to the Olympics, as you would expect, is significant. From the tried-and-tested stories of athletes battling against the odds to make it to London this summer. To the truly bizarre ones of the UK’s Ministry of Defence telling residents high-velocity rockets will be fitted to apartment blocks close to the Olympic Park. With round the clock surveillance, and even snipers.

Evidently, in the run-up to the games, tensions and expectations for worse-case-scenarios are high. The threat and danger of anything sparking a problem is clearly in the forefront of the organiser’s minds. With millions of extra people added to the melting pot it’s not just an extra strain on public services… it goes beyond that — the Olympics should come with a health warning.

Well, in fact, it does. A doctor at the Centers for Disease Control and Prevention (CDC) has told US travellers to make sure they are vaccinated against measles if they travel to London for the Olympics in July.

“Disease knows no borders. We are concerned about Americans coming back from the Olympics this summer and unknowingly infecting others,” Rebecca Martin, director of the CDC’s global immunisation division, told the newspaper USA Today (“US travelers to Olympics may bring home measles,” 19 March, 2012).

The immediate fear is that visitors will bring back cases of measles. The BMJ article cites the comparatively higher number of measles cases in England and Wales last year. In 2011, Americans imported an increased number of cases from other parts of the world, with nearly a third of those infected needing hospital treatment.

Which leads to the next logical question of how do you plan for a healthy Olympics? The simple fact of having a mass gathering of people inevitably points to the many health risks involved. Take for example, the Hajj “unique from an epidemiological standpoint: two to three million people from 70 countries meeting in one tiny place is the siren call for respiratory, water-borne and blood-borne microbial diseases”.

The Olympics are not all too similar to the Hajj, nevertheless, public health is a priority. With an extra influx of people from different parts of the world there is extra risk in terms of infectious disease.

Officials are going about to ensure that public health organisation during this time, and for the “legacy” that remains once the London Olympics and Paralympic games have long ended — is of the highest quality. And that entails knowing about any possible outbreak very quickly, and responding just as quickly.

“Getting ill isn’t a big risk” according to the Health Protection Agency’s London Regional Director, Dr Brian McCloskey.

To add to the usual modes of surveillance the Health Protection Agency usually employs for these type of mass gathering events, this time round Syndromic Surveillance will be used. Which differs from the usual type of surveillance used as it is not about what diseases people have but what symptoms people report to their doctor. Relying on prediagnostic data to estimate a community’s health status that proves a powerful early detection method.

Dr Brian McCloskey told a recent meeting at the London School of Hygiene and Tropical Medicine that the public health surveillance system, which has previously been used on a one-off basis for such events as the G20 summit in 2009, the Ryder Cup in Wales, and the visit of Pope Benedict XVI, will for the first time remain in place after the crowds disperse.

The London 2012 Olympic and Paralympic Games will cost £9.3bn (€10.7bn; $13.3bn), £150 for every man, woman, and child in the United Kingdom.

For this investment, the country has been promised legacy outcomes for sport and physical activity, regeneration, culture, sustainability, the economy, and disability.

At least one thing is somewhat certain; the Olympics might actually turn out to be better for the health and well-being of the country in the longrun.

Image — source

Originally appearing in Australian Science Mag

Tam, J., Barbeschi, M., Shapovalova, N., Briand, S., Memish, Z., & Kieny, M. (2012). Research agenda for mass gatherings: a call to action The Lancet Infectious Diseases, 12 (3), 231-239 DOI: 10.1016/S1473-3099(11)70353-X

McCartney, G., Thomas, S., Thomson, H., Scott, J., Hamilton, V., Hanlon, P., Morrison, D., & Bond, L. (2010). The health and socioeconomic impacts of major multi-sport events: systematic review (1978-2008) BMJ, 340 (may19 4) DOI: 10.1136/bmj.c2369

Tanne, J. (2012). US travellers to the London Olympics are warned about contracting measles BMJ, 344 (mar27 1) DOI: 10.1136/bmj.e2357


Koala trypanosomes…

This post was chosen as an Editor's Selection for

In an emergency room at Beerwah, Queensland, the phone rings almost 100 times a day.

The emergency room is one at the Australian Wildlife Hospital, providing veterinary care for sick and injured wildlife — admitting anywhere in the region of 30 different species on a daily basis — with injuries resulting from accidents, acts of deliberate cruelty, or conflict.

Arethusa came into the emergency room suffering from fractured ribs and internal abdominal bleeding. Frodo came in with a gunshot wound, sustaining a fractured skull and significant damage to the stomach and intestines. Travis and his mother were run over by a hit and run vehicle.

These four were koalas, but the hospital deals in animals common to the Australian landscape — from Brushtail Possums to Bearded Dragons.

The koalas themselves, cute cuddly creatures, with a sleepy demeanour, renowned as a representation of Australia have recently been in the news for being endangered and for a curious case of koala chlamydia. Koalas are in serious decline, suffering from many of the effects the veterinarians at the Australian Wildlife Hospital see on a daily basis — as well as habitat destruction, domestic dog attacks, bushfires and disease. The Australian Koala Foundation estimates that there are less than 80,000 koalas left in the wild, possibly as few as 43,000.

Over the past few years researchers have been distilling and putting together a case to add another reason for koala decline to the list. Roughly 600 koalas per year are seen to at the hospital, and most present with other primary conditions. A number of koalas, however, have presented at the hospital with serious illness associated with regenerative anaemia and now trypanosome infections.

The trypanosome is a parasite we commonly associate with African Trypanosomiasis (as well Chagas disease). In reality, the trypanosome also infects rats, cattle, and even kangaroos.

To say little is known about systemic and blood parasites of native wildlife in Australia would be an understatement. Researchers are only just beginning to understand the diversity of trypanosomes in Australian marsupials. Much is still to be learnt. Their evolutionary biology, transmission, and resulting potential impact on the wildlife. The possibility that indigenous wildlife trypanosomes can act as a reservoir for human pathogenic infections is all to be seen.

What we do know is that, in Australia, the introduction of trypanosomes are as a direct result of human activities. Being almost certainly responsible for introducing trypanosomes from one wildlife population to another. The vector — what transmits the parasite from animal to animal — of Australian trypanosomes is not known. Although, researchers have the flea in mind as the usual suspect.

To date around 10 trypanosome species and genotypes have been identified in marsupials; from the northern brown bandicoot, the platypus, the woylie, the chuditch, the eastern grey kangaroo, the common wombat, and the swamp wallaby.

The koalas that came into that emergency room over a two year period were systematically studied; collecting blood samples during routine veterinary examinations, detailing geographical origin, as well as sex, age and reason for admission. The standard patient history.

One such patient led to the description (morphologically, pathologically, and genetically) of a trypanosome in the blood. A new species, named Trypanosoma irwini… named in honour of the late great Australian Steve Irwin. A fitting tribute to an original patron of the Australian Wildlife Hospital.

Originally appearing at Australian Science Mag

Hamilton, P., & Stevens, J. (2011). Resolving relationships between Australian trypanosomes using DNA barcoding data Trends in Parasitology, 27 (3) DOI: 10.1016/

McINNES, L., GILLETT, A., RYAN, U., AUSTEN, J., CAMPBELL, R., HANGER, J., & REID, S. (2009). Trypanosoma irwini n. sp (Sarcomastigophora: Trypanosomatidae) from the koala (Phascolarctos cinereus) Parasitology, 136 (08) DOI: 10.1017/S0031182009006313

Thompson, R., Lymbery, A., & Smith, A. (2010). Parasites, emerging disease and wildlife conservation International Journal for Parasitology, 40 (10), 1163-1170 DOI: 10.1016/j.ijpara.2010.04.009

The Death of TC-5214…

All too often, experimental drugs post stellar results from studies conducted in Russia, India and other less developed regions, leading to inflated stocks for the company and misplaced hopes. Only to blow up after the data cannot be replicated in the United States or Europe.

TC-5214 is one such example.

Targacept Incorporated is a biopharmaceutical company that is in the business of creating a new class of drugs that treat multiple diseases and disorders of the nervous system. The drugs they design and engineer selectively target the neuronal nicotinic receptors (NNRs) that are widely distributed throughout nerve cells of the central nervous system. TC-5214 is one such class of compound.

In fact, over the last ten years more than 1000 articles have been published describing the use of these types of compounds (mecamylamines) as a pharmacological tool to confirm the involvement of nicotinic receptors in various physiological and pharmacological effects.

In the winter of 2008, a paper was published that spoke to the potential therapeutic benefit of modulating activities of these NNRs in the central nervous system.

Functional NNRs are widely distributed in the brain, and numerous studies have shown that mecamylamine blocks nicotinic-induced mnemonic effects in normal and aged animals and in humans.

TC-5214 (or mecamylamine) acts as a noncompetitive NNR antagonist, and showed some positive effects in a number of animal models of depression and anxiety.

The forced swim test (the behavioural despair test or the Porsolt test) is a test frequently employed as a measure of the effect of antidepressant drugs on the behaviour of lab mice or rats. The procedure is simple. The mice are subjected to two trials during which they are forced to swim in an acrylic glass cylinder filled with water. One from which they cannot get out. The first trial, lasting 15 minutes, is followed by a second after 24 hours, lasting just 5 minutes. The measure is the time that the animal spends without moving in the second trial. And this immobility time is decreased by antidepressants. With immobility taken as a behavioural correlate for a negative mood.

TC-5214 was active in the forced swim test in rats and it was also active in the behavioral despair test in mice. The researchers concluded that their results support a novel nicotinic cholinergic antagonist mechanism for antidepressant and anxiolytic (anti-anxiety) effects and highlighted the potential of NNR antagonists as therapeutics for the treatment of anxiety and depression.

Today, TC-5214, representing the most promising drug in the Targacept Inc. pipeline, has come to a screeching halt after it failed the final two clinical trials for major depressive disorder. TC-5214 was positioned to be an add-on treatment to existing anti-depressants.

Targacept’s TC-5214 compound previously failed two short-term Phase 3 clinical trials in 2011, showing no significant difference in patients when compared to a placebo. The company needs two successful results to pursue Food and Drug Administration’s approval of the compound. As such, with this recent failure, the pursuit of TC-5214 as a possible treatment has been abandoned.

This fail of a drug happens all the time. But this one arouses a certain facet of the discussion. Namely, the difficulty in reproducing clinical trial results across different countries. TC-5214 showed outstanding results in Phase 2b clinical trials in India, but that level of excitement failed to be reproduced in the USA (the only country that counts for FDA approval).

Image — source.

Originally appearing at the All Results Journals

Fedorov, N., Benson, L., Graef, J., Lippiello, P., & Bencherif, M. (2008). Differential Pharmacologies of Mecamylamine Enantiomers: Positive Allosteric Modulation and Noncompetitive Inhibition Journal of Pharmacology and Experimental Therapeutics, 328 (2), 525-532 DOI: 10.1124/jpet.108.146910

Lippiello, P., Beaver, J., Gatto, G., James, J., Jordan, K., Traina, V., Xie, J., & Bencherif, M. (2008). TC-5214 (S-(+)-Mecamylamine): A Neuronal Nicotinic Receptor Modulator with Antidepressant Activity CNS Neuroscience & Therapeutics, 14 (4), 266-277 DOI: 10.1111/j.1755-5949.2008.00054.x

New routes to Chagas…

On March 5th 2001, a 37 year old woman went into surgery to have a kidney and pancreas transplant from a donor that had already passed away. Once discharged, she returned to the hospital six weeks later to be treated for a sudden onset of fever (of unknown origin). She would die six months later, on the first week of October.

What turned out to be the first recognised case of a T. cruzi infection through solid-organ transplantation in the Unites States, came after the physician identified the parasites in a peripheral blood smear. Upon identification the physician immediately notified the Centre for Disease Control (CDC). Upon further investigation it was discovered that other patients had received infected organs from the same donor. A 32 year old woman who had received the liver, and a 69 year old woman who received the other kidney. Both organs were found to be infectious. The donor of the infected organs was an immigrant from Central America.

At the time, no protocol or policy was in place for the regular screening of organ donations for T. cruzi — something that was routinely done in Chagas endemic areas. And no test was licensed for screening organ or blood donors. Today, two Chagas tests are available, out of a full complement of 60 that are licensed and routinely used to screen organs and blood donation for a wide range of infectious agents (including HIV, hepatitis, and west nile virus).

After the infection was detected, all three women were treated with nifurtimox — a drug not available in the US at the time. And a drug, over ten years later, still only has a single manufacturer. Today, nifurtimox, a drug that dates back to 1960, is available for US$48 per treatment regimen — the equivalent of a month of a Bolivian miner’s salary.

Of the three women that were infected, it was only the 69 year old woman that would survive the parasitic infection. In the most severe case, it was death as a result of immunosuppression. The woman who received the kidney and pancreas transplants, was the most immunosuppressed of the three patients. She died even after completing a full course (4 months) of treatment with nifurtimox.

Dorsal view of the “kissing bug”, Triatoma infestans

The original organ donor, the immigrant from Central America, most likely acquired Chagas from the triatomine kissing bug. As it bites, the insect carrying the parasite deposits faeces on the victim’s skin, and when the person rubs the bite wound, the faeces containing the parasite enters the bloodstream.

Blood and organ donor screening programs across the Americas and North America have essentially eliminated transmission via this way. However, some cases still turn up. Add to that the lack of awareness of the disease among US healthcare providers complicates the issue.

Chagas, once thought of and regarded as an exotic disease, given little attention, is increasingly being diagnosed in non-endemic areas. In 2009 it was estimated that 300,000 people living in the US were chronically infected with the parasite. In Europe, Chagas has been reported from congenital transmission (from mother to infant), in a recipient of a bone marrow transplant, and among Brazilian immigrants of Japanese origin in Japan.

Patterns of emigration have drastically changed the epidemiology of this disease over the recent decades. Immigration is one reason, but not the only one.

A new study has shown that a high proportion of triatomine bugs collected in Arizona and California had fed on humans, while others were positive for T. cruzi parasite infection. This new study essentially indicates that the potential exists for vector transmission of Chagas disease in the US. Up until now, the most common result of a triatomine bite was an allergic reaction.

Featured image — source

Triatomine image — source

Originally appearing at Weir, E. (2006). Chagas disease: hidden affliction and visible neglect Canadian Medical Association Journal, 174 (8), 1096-1096 DOI: 10.1503/cmaj.051442 Machado, F., Jelicks, L., Kirchhoff, L., Shirani, J., Nagajyothi, F., Mukherjee, S., Nelson, R., Coyle, C., Spray, D., de Carvalho, A., Guan, F., Prado, C., Lisanti, M., Weiss, L., Montgomery, S., & Tanowitz, H. (2012). Chagas Heart Disease Cardiology in Review DOI: 10.1097/CRD.0b013e31823efde2 Stevens, L., Dorn, P., Hobson, J., de la Rua, N., Lucero, D., Klotz, J., Schmidt, J., & Klotz, S. (2012). Vector Blood Meals and Chagas Disease Transmission Potential, United States Emerging Infectious Diseases, 18 (4), 646-649 DOI: 10.3201/eid1804.111396

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