Archive for January, 2013

The animal link to sleeping sickness…

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As with many parasites, the nuisance they bring is partly compensated for by new insights they provoke. The African trypanosome is perhaps unique among all of the diseases of developing worlds. The diseases of sleeping sickness, inflicted on man and cattle alike, perhaps drove early man ‘out of Africa’ — in an attempt to avoid tsetse infested areas of the Rift Valley. The Zulu word for powerlessness and useless, “N’gana”, describes the disease in cattle — listlessness, emaciation, hair loss, and progressing towards being fatal.

Human African Trypanosomiasis, a disease David Livingstone initially linked to the bite of the tsetse fly because the cattle on his expedition died, is one of the many “tool-deficient” tropical diseases. Despite this, unprecedented progress has been seen over the past few years, according to the WHO. Today there is an upbeat picture painted of the disease burden in humans. Since 2009, the number of new cases in humans, for the first time in 50 years, has been fewer than 10 000. That is a 72% decrease in the last 10 years alone. This gain in momentum over the decades has lead those involved to think of one thing — elimination and eradication. Whispers on the lips of many are now full-throated calls to action. The worry has always been that the official numbers perhaps aren’t the entire picture, with many more cases going unreported.

It seems now there may be another threat to eradication efforts. Namely, the potential for animal reservoirs to maintain and cause a resurgence of the disease. New research published in PLOS Computational Biology uses a mathematical model to show that the West African form of the disease not only can persist in an area even when there are no human cases, but probably requires the presence of infected wild animals to maintain the chain of transmission.

The problem is an unusual puzzle. T. brucei rhodesiense is the animal form of the disease, while the more chronic west African form, caused by T. brucei gambiense, is the cause of the human form of the disease that accounts for around 95% of reported cases. Gambiense trypanosomiasis has been found in domestic and wild animals. Whether this source of the disease serves as a significant form of transmission to humans is the question.

On the small island of Bioko in Equatorial Guinea, trypanosomiasis has been eradicated. The last case of Gambiense was 18 years ago. But, curiously, the parasite has been detected in flies that inhabit the island. The simplest explanation is that animals are no more than an inconsequential dead-end host. But how did the human parasite get there without any human cases to spread it to animals? It means that the parasite is still within the animal population. Existing as a low-level animal reservoir. And this is the most threatening fact of all — forewarning the possibility of igniting the disease again in humans — possibly jeopardising eradication efforts.

What researchers tried to do was to try and quantify the contribution of the different species to the circulation of the parasite. They took, as their sampling population, Bipindi in Cameroon. A well-known location where both animal and human case data could be collected.

What they found was that animals do play a part in maintenance of the disease, finding indications of independent transmission cycles in animals. The implications are plain — that a risk of reintroduction from animal into human populations would still be possible even when the disease was eliminated from human populations. The author’s write “…this study offers an attractive explanation for the mysterious disappearance and re-activation of gambiense foci throughout Africa.” Indeed, the decline of Gambiense sleeping sickness across much of West Africa might be mainly, and simply, down to reduction in wildlife populations, and further efforts on the disease must take into account the wild animal populations.

It’s a study that is fascinating and one that definitely warrants further research. This animal link has, for the most part, up until now, been largely sidelined. The effort to reducing human cases will continue and no doubt be amplified. The question that remains to be seen is if animal cases are a big enough threat to make an impact on the human eradication.

Originally appearing in Australian Science

Image — source, source

ResearchBlogging.org

Funk, S., Nishiura, H., Heesterbeek, H., Edmunds, W., & Checchi, F. (2013). Identifying Transmission Cycles at the Human-Animal Interface: The Role of Animal Reservoirs in Maintaining Gambiense Human African Trypanosomiasis PLoS Computational Biology, 9 (1) DOI: 10.1371/journal.pcbi.1002855

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Morphine hurts…

syringe

Why does Morphine cause pain?

He was diagnosed with testicular cancer at the age of 27. At the age of 39 he was in so much pain he begged his doctors to die. He was in pain because of morphine. In the 12 years he lived since he was diagnosed he had a therapeutic regimen that allowed him to have a good quality of life. His pain was controlled by bursts of sustained-relief morphine twice a day. Up until a family trip in November of 2000 there were no problems. Then the pain got inexplicably worse.

“Beating, shooting, stressful, squeezing, piercing, constant and terrifying” were the words he used to describe his torment. Any movement made it worse. In the end he had to lay “very, very still” to find some respite. But this didn’t last for long. Nothing his doctors tried worked. The pain was unrelenting. “If this is the level of pain I have to live with, then I want to die”. Serious words that go some way to emote the pain. As the pain remained his regimen of painkillers was increased. Still, the pain remained. He asked to die again. His wife supporting his decision. After drastic measures and attempts to reduce the pain with no success the decision was made to proceed with terminal sedation. He had gotten his wish to die peacefully. And since pain control was futile, his medication was ceased.

This was when things improved. Without a heavy regimen of morphine, hydromorphone, and ketamine, the pain began to subside. He lived out the remaining 6 weeks of his life pain-free.

His case was not uncommon. What he experienced was opioid-induced hyperalgesia, an important phenomenon seen with high-dose opioid therapy. Morphine, named after the greek god of dreams, has been used as a potent painkiller for eras. Perhaps since the days of the Byzantium Empire. For years the phenomena of morphine causing pain has been paradoxical and largely unresolved. Unresolved, that is, until the January 6 edition of Nature Neuroscience.

“Our research identifies a molecular pathway by which morphine can increase pain, and suggests potential new ways to make morphine effective for more patients,” said senior author Dr. Yves De Koninck, Professor at Université Laval in Quebec City in a press release. “When morphine doesn’t reduce pain adequately the tendency is to increase the dosage. If a higher dosage produces pain relief, this is the classic picture of morphine tolerance, which is very well known. But sometimes increasing the morphine can, paradoxically, makes the pain worse,” explained co-author Dr. Michael Salter.

Their research points to a new pathway to how morphine acts. Tolerance of morphine is one thing (when increased doses do not produce the same effect), but hyperalgesia refers to an increased sensitivity to pain with morphine. So how are these two distinct features of the same drug satisfied along the same pathway of action?

When morphine relieves pain, it relieves it in the spinal dorsal hornand then in the brain. The former is a part of the spine that will receive pain signals from receptors and send them on towards the brain (via lamina neurons). These neurons are central targets for pain relief (analgesia). Morphine brings about pain relief by inhibiting these neurons.

The pathway towards pain sensitivity they came up with was a cascade, initiated by morphine that leads to the lamina neurons and eventually deregulates chloride ions. And it is these chloride ions, out of sync and homeostasis, that causes pain hypersensitivity. In their study they managed to adequately separate the different components of hyperalgesia from somple tolerance.

The picture the researchers paint is that tolerance and hyperalgesia are functionally distinct. Makes sense as the clinical characteristics are also distinct. However, what they propose is still a long way off any practical solutions for actual patients that suffer pain from morphine, but a big step in the right direction.

Originally appearing in Australian Science

Image — source

ResearchBlogging.org

Wilson GR, & Reisfield GM (2003). Morphine hyperalgesia: a case report. The American journal of hospice & palliative care, 20 (6), 459-61 PMID: 14649563

Ferrini, F., Trang, T., Mattioli, T., Laffray, S., Del’Guidice, T., Lorenzo, L., Castonguay, A., Doyon, N., Zhang, W., Godin, A., Mohr, D., Beggs, S., Vandal, K., Beaulieu, J., Cahill, C., Salter, M., & De Koninck, Y. (2013). Morphine hyperalgesia gated through microglia-mediated disruption of neuronal Cl− homeostasis Nature Neuroscience DOI: 10.1038/nn.3295

Vaccinating the Haitian Cholera…

Haiti struggles through many things — earthquakes, hurricanes, and disease. Cholera, first and foremost, seemingly brought to the country by the very people trying to help it. The UN aid workers were pinpointed as the source of the outbreak.

There is much talk of vaccinating for cholera in Haiti. Many believed it wouldn’t work and to get the coverage needed for it to be effective was virtually impossible given the nature of poverty within the population. The reasons were numerous and voiced. In April of last year, vaccinations finally started, and it has seemed to be somewhat successful.

New research, published in Nature’s Scientific Reports, adds more wait to the usefulness of a vaccination campaign for cholera in Haiti.

“You don’t have to immunize everybody. Even if we could get an immunization rate in the range of 40 to 50 percent, it should be possible to control recurrent cholera outbreaks,” Dr Morris of the Emerging Pathogens Institute in Florida, said in a press release. “That should be enough to tilt things in your favor so that you can start getting control of the disease in these areas, to where, hopefully, rates of transmission will slow and numbers of cases will gradually die off.”

Haiti’s population was immunologically naïve to cholera after its long absence, so the potential for a severe cholera epidemic was high, and there was the fear that the outbreak would establish a long-term endemicity, marked by the traditional recurrent seasonal epidemics.

The paper ends by mentioning the obvious caveat of them all; “However, to achieve optimal protection of the population, vaccination would need to be combined with other measures that permanently improve water systems and/or otherwise decrease the risk of transmission from environmental sources.”

Predicting the next epidemic…

Emergency hospital during influenza epidemic, Camp Funston, Kansas.

Emergency hospital during influenza epidemic, Camp Funston, Kansas.

In some parts of this world the rains predict disease, and a hot, dry, dusty wind is the harbinger of a meningitis outbreak that is yet to come. Now, from where you sit, Google will soon predict the next great epidemic.

At this time of year, ever since that 2009 paper was published on flu trends, seasonal influenza and how we predict it, is a recurring topic.

It seems we are always moments away from the next great flu epidemic. This year saw a novel coronavirus make the rounds. A virus that usually causes nothing more serious and common than a cold, was the source of severe respiratory illnesses in the Middle East, with reported cases coming from Qatar, Saudi Arabia and Jordan, and resulting in 5 fatalities.

The curious case of the novel coronavirus is a new strain of virus that has not been previously identified in humans. The hypothesis is that it jumped the species barrier, but, as of yet, a definitive origin has not been identified.

When a disease will decide to jump the species barrier is hard to predict. Some of the most serious afflictions of humans in recent times have had their origin in animal diseases. HIV/AIDS and ebola being the prime example. Seasonal influenza is another — causing tens of millions of respiratory illnesses and up to half a million deaths worldwide each year.

In mankind’s eternal struggle against disease, as the adage goes, prevention is better than a cure. But how do we prevent disease? How do we mitigate for an oncoming plague or pestilence? A part of this prevention is predicting it.

Currently, we can only really predict an epidemic when it is currently in motion. Hospitalizations are the only way we can really track a disease. When it is possibly already too late. When people are already sick.

In the week the world was supposed to end, the European Centre for Disease Control (ECDC) released its weekly report on influenza surveillance, like it had done since week 40 of this year. The report aggregates data on influenza-like illnesses reported in primary health care facilities, as well as virological and clinical data.

Flu surveillance, in Europe and similarly in the US, is based on nationally organised sentinel networks of physicians, mostly general practitioners (the first person you go see when you’re ill), covering at least 1 to 5% of the population in their countries. Each sentinel physician reports the weekly number of patients seen with influenza-like illnesses and acute respiratory illnesses.

The report is essentially there to tell us when a flu epidemic is going to break out. In week 49, ECDC announced that the season of influenza transmission had begun.

Along with the direct methods of detecting and monitoring disease, in recent years new and innovative non-direct methods have been tested. From sales of over-the-counter medication to online activity. The idea is to try and record health-seeking behaviour… ie before the disease has taken hold in a population.

Emergency hospital during influenza epidemic, Camp Funston, Kansas.

Monitoring disease, 140 characters at a time…

Flu is a disease very amenable to being searched and turning up in social media. Health-seeking behaviour — in this day and age, we google every ailment. However, diseases which are more serious probably won’t follow this social pattern.

The concept is essentially trying to “predict the present”. Google flu trends isn’t the only one to mine social data. Mappyhealth mines twitter data, tracking 25 conditions from around 200 health related terms. Searching for the spikes in activity from those certain key terms. Spikes in activity above the social noise, pointing to a significant event associated with the term. In some places it has been shown to be a good indication of the real underlying movement of disease.

But what of diseases that are not as commonplace as the flu? How would google or twitter act as an early warning system for diseases of a tropical nature?

2.5 billion people are living in areas at risk of Dengue fever, otherwise known as breakbone fever — a painful and sometimes fatal viral disease characterized by headache, skin rash and debilitating muscle and joint pains. In some cases, it can lead to circulatory failure, shock, coma and death. There are up to 100 million infections a year — and it’s growing. Incidence and geographic distribution of dengue has gone up in many countries, spurred on by a changing climate.

So how do we predict a disease that is more complicated than simple person to person transmission? What if there is another step to overcome — namely, in the case of dengue, a mosquito? Early warning systems for vector borne diseases are incredibly complex.

Google Dengue aims to do the same thing flu trends did. And the results are remarkably similar. Google search volume for dengue-related queries were able to adequately estimate true the dengue activity and official reported cases. The realisation that disease can be tracked in this manner is a relatively new occurrence. Few have explored non-traditional settings for monitoring epidemics, dengue or otherwise.

The caveat, however, is obvious — a term turning up in a search term doesn’t necessarily point to the presence of the disease. “Now-casting” (as opposed to forecasting) using a web-query based surveillance depends on a few crucial factors. First and foremost is the evident internet availability — and in developing countries this might prove difficult.

Despite its limitations (panic-induced searching from the announcement of a novel outbreak, backed up by media sensationalism), it proves effective and, most importantly, low cost. Up-to-date and accurate estimations of disease lets the health professionals make an effective response to the moving disease. In the case of influenza, where a vaccine is available, it makes sense. In the case of dengue, all that remains is a working vaccine for this method to live up to potential.

Image — sourcesource

Originally appearing in Australian Science

1.1 Million cases of Norovirus…

Yep. Over 1 million in the UK this season. And the reason? A new type of the virus is making the rounds.

The 1st molecular data uploaded to the international molecular surveillance database NoroNet from Australia, France, New Zealand, and Japan indicate that this increase is associated with emergence of a new variant of genotype II.4 (GII.4). The 1st report of this variant was from Australia in March 2012 (personal communication P.A. White, September 2012), and the strain sequence was submitted to GenBank (accession number: JX459908.1). In the United States (US), the variant (named Sydney 2012) was detected in September 2012 in five of 22 (23 percent) laboratory-confirmed outbreaks, and in November in 37 of 71 (52 percent) laboratory-confirmed outbreaks (recorded in the US norovirus surveillance network CaliciNet) [4]. In 2 European countries that have not reported any indications of increased activity, the new variant has been found in outbreaks, 2 in Belgium (September and December 2012) and one in Denmark (November 2012). Other countries participating in NoroNet have not yet reported the new variant.


What had I twaught…


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