Her name was Poppy – my first ever pooch whom guided me from my pre-Mexican bandit facial hair days, through to a completely new era in my life, as she bid me her final farewell during my first week of Edinburgh University. Half German Shepherd – Half Total Fluffpot, my fondest memories of her include her attempt to bite a douchey fella who walked in that douchey way whilst giving some douchey agro to my Dad on a walk… and her devout company throughout that 5 set Wimbledon Epic between Federer and Nadal (I think she wanted the tennis balls…..). A wonderful dog, with a golden mane, golden heart..and an exquisite talent for delicately unwrapping chocolate bars from underneath the Christmas tree (True story!).
“She has Cushing’s Disease” came the weighted words of the Dog Doctor, or Vet if you will, towards her final days of duty as our ultimate guard dog. Poppy had been through a few veterinary scraps throughout her time with us…but her old age and progression of the condition would not allow us to see her through this one. The time to rest had come.
Cushing’s syndrome itself is the name given to the signs and symptoms attributed to prolonged and inappropriate exposure to elevated glucocorticoids such as the stress hormone – Cortisol. Our dear Pops was believed to have had a corticotroph adenoma, which results in excessive levels of secreted Adrenocorticotropic hormone (ACTH) and stimulates, down the line, the adrenal cortex, which is embedded in endocrine glands situated at the top of our kidneys, to produce ridiculously high levels of cortisol.
The long term results of exposure to this stress hormone are Weight gain & Obesity, high blood sugar levels (Hyperglycaemia) and loss of skeletal muscle mass. We humans get it too! Additional things more obvious in homo sapiens include the development of ‘buffalo hump’ – fat depots over the thoracocervical spine (about mid-way down on the back) – as well as bright red-purple striae (stripes/bands/lines) over 1 cm in width, around the abdomen. Given that the hyperglycaemia persists and continually stimulates the secretion of that all important hormone insulin from the pancreas to help control blood sugar levels, you might describe this aspect of the condition as a type of Type 2 Diabetes Mellitus. However, the rise in insulin levels do not effectively reduce the blood sugar levels because the skeletal muscle and fatty (adipose) tissues don’t take up the glucose, which is in higher availability in the blood, as much as they should.
Dear ol’ Pops passed the Dexamethasone suppression test, by showing no suppression of ACTH and cortisol secretion upon administration of external, supraphysiological doses of glucocorticoids….thus confirming her condition. Whilst the removal of the adrenal adenomas would have fixed the high cortisol level issue, her overall condition and age hindered the certainty of cure over further risk.
At least a few times a month, she’ll trot into my dreams, roll onto her back and beg for a tummy tickle though! Silly Pops…. Happy Christmas and New Years in doggy heaven…which I imagine to be some sort of wood with trees that grow Bonios.
Never mind the glorious Victoria Secret types (well….). There are other kinds of wonderful models in this world. StatisticalModels, Public Health Efficacy models and low and behold….Animal Models.Often the target issue of animal right activists against the world of dirty pharma (and rightly so), animal models do and have played an insightful role into how medicines work before giving them a go in us human likes. A couple of success stories from this website gives a very brief insight into new-found treatments for PTSD, Memory problems and Polio for example. Animals have also helped recently in our understanding of Rheumatoid Arthritis pathophysiology.
In 2012 I took it upon myself to investigate Animal Models and their use in a specific area of neurophysiology – looking at the movement disorder ‘Parkinson’s disease‘ or PD. I knew from the start it would be tricky business, for example – does the Substantia Nigra (one of the warzones in the PD brain) of a glorified rat really represent the human Substantia Nigra? But still, I knew a good bunch of reasons for animal research to help understand important conditions such as PD.
I wanted to investigate how animal research has helped in our understanding of the relationship between genetic causes and environmental causes in the origin and progression of this movement disorder. Under the guidance of some statistical wizards and a Professor who always had to put his feet up on something when he talked, I was led to the epicentre of a scientific nightmare.
Out of 23 animal research studies I analysed with rigorous statistical methods and several Pick ‘n’ Mixes from the downstairs WH Smiths, a grand total of zero bothered to ensure the person investigating the results of their experiment were ‘not in the know’ of the experimental animals and the control groups. This of-course increases bias and bias is the very thing any clinical trial would want to avoid. And so why should a pre-clinical study, in animals, which require trillions of hours of the sharpest brain-work and a fair amount of funding, be any different? Save time and money at the start in this animal research, and quicker we may be onto the path to success in finding the answer to BIG questions such as the Origin of Parkinson’s disease, or how it progresses, or how best to treat it. Sure yes, I’m picky on the one point here but it’s a big point, and other parameters in these studies were poorly controlled to.
Nonetheless – some physiological considerations to ponder upon did crop up. Namely, a mutation (A53T) in a gene called alpha-synuclein appears to be enhance the negative effects of one potent environmental toxin that causes PD symptoms – a molecule called MPTP. As with many areas of Parkinson’s disease research, the energy factories of our cells – Mitochondria – appear to hold the link here too.
Whilst the picture is of PD causality and pathophysiology is building, a slicker methodology shouldn’t be overlooked in the next round of audits. Only then can the masterpiece truly take shape. Only then can we be certain to find real answers (a cure, perhaps?) to real problems. Only then, can we hope to replace, reduce and refine animal models in medical research.
2 months on from turning 24, I’m still finding it difficult to come to terms with the ordeal. It feels like yesterday when a younger friend turned to me and said “Jeees Phil tomorrow you’re seventeen! Gettin’ old man….” and now after a quick head-to-toe examination in the mirror, I take in the battle-wounds accumulated since; A freckle on my nose from when I squeezed a spot in earnest (probably a little too hard); A couple of shaving scars from whenever I obliterate my admirable attempt of a Confucius beard; A lower left leg scar gifted from the door of a deluded Taxi driver……..and a pair of ‘not-quite-fully-recovered’ ankles from when I battered the streets of London in the Marathon of 2009. Not a great deal to report on the exteriors to be honest. But deep inside the cells of the tissues of the organs of the Phil….things are going nutz!
Inside a cell, it’s virtually a whirlwind Blockbuster day-in and day-out. The genetic components in each of our cells, which provide the necessary information to produce proteins so you appear the way you do, are packed densely within chromosomes. Each of our chromosomes have “end-caps”, called telomeres, that play an important role in stabilising the end of chromosomes, because the ends of chromosomes tend to be a bit vulnerable you see (just like the outer penguins in a colony to the bitter cold). These telomere ends do not contain any active genes themselves but instead contain a variety of highly repeated DNA sequences and special proteins which form a unique structure at the end of a chromosome.
In my somatic cells, or more particularly – most cells other than my germ cells, circulating stem cell populations (haematopoetic cells for example) and my highly proliferative skin cells – my telomeres have gradually been getting shorter and shorter upon each division. As these cells divide throughout ageing, the ‘end-caps’ erode away causing the cells to malfunction or die. Only in those highly proliferative cell types are telomeres able to not only maintain their length but extend it, courtesy of a unique RNA transcriptase enzyme called telomerase.
Don’t get me wrong, there are perks to being 24 as opposed to 17 regardless of my depleting telomere lengths. Not having to put my hand up to go to the toilet is one of them! But there’s serious stuff to this business. Research leads us to believe that the telomere shortening mechanism sets a limit on the lifespan of a cell, thus heavily contributing to the process of ageing at a cellular level. Also, abnormalities in telomere regulation can lead to cancer - typically down to missed checkpoints on the path to senescence (limited replicative potential) as telomeres become shorter, and an overactivation of the enzyme telomerase.
So can we avoid cancers and keep our telomeres long?
A small pilot study published in The Lancet Onocology earlier this year suggests that making positive changes in our diet, stress management and social management may result in longer telomeres. Sounds optimistic, but worthy of our attention.
And so here’s to a long and happy life and a bright future full of youthful codgers……unless our Telomeres go AWOL.
Elizabeth Blackburn, Carol Greider, and Jack Szostak were awarded the 2009 Nobel Prize in Physiology or Medicine for the discovery of how chromosomes are protected by telomeres and the enzyme telomerase.
I will certainly get around to that Will Smith & Ali post some-time soon!
While the game of patience, CV-rewrites, recruitment calls and casual “I’m a solid team-player” line-drops continue – I’ve had a chance to read this bad-boy, along with Animal Farm and a layered spy novel by Ian McEwan (thoroughly enjoyable!).
A Bit of Background
My analysis of one of the most socially networked open access articles (from PLoS) is fairly vague (no false advertisement here), but the paper made me laugh and the title, like it did me, probably had most people in disbelief on first glance. Now, Open Access Journals (OAJs) often come under fire for their quality, by which I mean the scientific rigour of the research within a publication and to what level the submissions are actually screened, known as the peer review process. Indeed, only a few days ago we have witnessed the results of a brilliantly crafted Sting Operation which highlighted the desperately worrying trend of novel OAJs appearing with fictional editors and fabricated institutions along with miserable peer review performances. I mean – truly dismal performances. Well done John Bohannon! Despite this, PLoS faired well in the Sting Operation despite more general concerns from academics over the quality of scientific papers that PLoS typically publish. All the more reason to give this ‘In depth analysis of a piece of …….’ paper a read and see personally whether its’ conclusions have any grounding.
A hilarious title is not completely novel in academic research – take this one about coked up honeybees for example, or any on this list compiled by WIRED magazine. Either way, the concept of this actual study is well within reason and there are some interesting and important implications to come out of the sound findings, such as how Doctors determine the diagnosis of a helminth (parasitic worms) infection and potentially how future studies, which determine the effect of medicines designed to act against these worms (antihelmintic drugs), are designed.
I made a friend in Vietnam who wanted to focus her PhD on intestinal worms. She had this cool hypothesis (that was still a growing idea) about immune system and worm ecology, which made me scratch my head for struggling to understand better, but she never told me just how big of a worldwide issue they pose. The WHO reckons that about 24% of the World’s human population is infected with a soil-transmitted helminth. Now this doesn’t have to mean it’s an issue – but it can be. Especially if you’ve been infected with a relatively big load of them, which can lead to diarrhoea, stomach pains, neural impairments and blood loss. Epidemiological surveys, which typically investigate stool samples for evidence of parasitic worm eggs, show the highest burden lies in the tropics and sub-tropics. However despite knowing this and having drugs available to control helminth infections, public health researchers and clinicians commonly share the concern that helminth infections represent, with immensity, a neglected tropical disease.
Hence the study holds two ultimate aims, 1) to determine whether the eggs of helminths Schistosoma mansoni and Hookworms exhibit any particular spatial distribution in the piece of, erm…ahem….faecal matter… and 2) tounderstand what might constitute a more accurate diagnosis. Sounds like a perfectly reasonable endeavour for the advancement of medical knowledge for such a high burden disease right? Yes (say yes).
The Study’s Execution
222 individuals from Ivory Coast were invited to participate in this study. For the ‘field collection’, the instructions as presented in the ‘INSTRUCTIONS’ figure below, were given to all participants. Notice that the timing is recorded, which is particularly important as the time delay from the stool production appears to influence diagnostic sensitivity – especially for hookworm.
There is such a thing as the Bristol Stool Chart (BSC; nice one Bristol!) which is a medical aid to distinguish human stools into categories. Here, the authors place specimens into 5 distinct categories:
1) Sausage-shaped (equivalent to type 3 on the BSC)
2) Sausage-shaped but lumpy (type 2 BSC)
3) Sausage-shaped but soft (type 3 BSC)
4) Lumpy (Type 1 BSC)
5) Mushy (Types 5-7 BSC).
…and then (randomly) either underwent whole-stool homogenisation (high frequency mushing, often performed with tiny silicon beads) or underwent direct helminth egg spatial disbtribution examination by drawing lots. Regardless, fecal egg counts (FECs) were taken before and after homogenization.
The authors are very thorough in explaining what they did, giving details of how deep the cut into the faecal samples and the tools they used throughout. They also give a solid account for time as a confounding factor and therefore, randomly allocate the times of stool sample analysis, with each examination time point lasting 2 hours. No qualms here – brilliant stuff. However, what exactly are the four distinctive examination time points that these researchers claimed to have established? Why not mention what they are at least once throughout the paper? Wouldn’t future researchers / diagnostic teams want to know???? Bizarre. Also, the researchers follow WHO guidelines for the Kato-Katz ‘thick smear’ preparation and examination which is common practice, despite the authors indicating shortcomings of this method from the start-off (see below).
Regardless of the processing schemes, an approximate third of all samples were stored in the following manners to determine their effect on egg degradation, with the obvious aim to determine how best to store stool samples in the future for accurate helminth diagnosis:
1) Stored in a box on ice
2) Stored covered with a tissue soaked with tap water
3) Placed in shade outside of the laboratory without any additional preservation effects.
* We are never convincingly told exactly why the above storage methods were chosen. I suppose we are meant to assume that these are typical storage procedures during helminth diagnosis. However, because of relative uncertainty of how best to go about storing these stool samples, it makes for interesting commentary in the results.
This is how to do it – Field Workers: Watch and Learn! This is what I want to see in every set of instructions I see from now on. Something I can relate to. Direct. Clear. Scientifically astute. Makes me laugh.
So, prior to homogenisation, the researchers chopped the ‘sausage shaped’ faecal samples into four pieces and performed the Kato-Katz procedure on central and surface areas, in preparation for the search of parasitic worm eggs.
* The investigators are using the Kato-Katz method to process the stool samples in preparation for the search of eggs. This is still a common procedure however, even the authors state problems of reliability in the detection for parasitic eggs in faecal samples. So if the intent of study is to get to the bottom of helminth distribution in faeces, why not go one step further by utilising other tests to strengthen the validity of results, such as this.
Not really! They’re quite cool actually. Of the 222 participants, 125 were positive for helminth infection, but only 116 had enough stool for analysis (52.3%). There’s an approximate third split for the storage method, followed by categorising the samples into ‘suitability of assessment’ for
- egg location along the length axis (n = 45)
- egg location along a cross-sectional axis (n = 35)
And then, OF THESE, also…..
- homogenisation of stool parts (n = 62)
Note: 53 ‘whole stools’ (i.e. they are not cut up into tidy pieces) undergo direct homogenisation.
By then performing Kato-Katz thick smear preparation and microscopy examination, the investigators identified five different helminth infections under varying prevalences and infection intensities. Amazingly, 5.6% of infected samples showed evidence for TRIPLE worm infection, with 20% showing DOUBLE worm infection. They sure do get about…. It’s important to note that for the rest of the statistical anaylses, the investigators only ever really focus on S. mansoni and Hookworm.
SPATIAL DISTRIBUTION: No clear pattern was observed although in hookworm infected individuals, higher egg counts were significantly noticeable in the front-ermost piece of stool sample than the back-ermost piece.
TIME and STORAGE in EGG DECAY:
- For Schistosoma mansoni the egg count results did not differ between the different time points regardless of how they were stored.
- For Hookworm positive samples, it’s a different story. The egg counts do decay over time UNLESS if samples were stored on ice or ‘kept humid’ they say – which I assume means ‘covered with water soaked tissue’???
* No reporting of a blinded assessment of outcome. This is a shame really, considering the investigators were on a good roll (concerning laboratory practice) by stating randomised allocation of the 5 different categories of stool samples into either full stool homogenization or ‘piece’ homogenization.
* Even though the statistical analyses back up their findings, we’re only dealing with one immediate population from Ivory Coast here. However, it has to start somewhere and this is a step in the right direction towards a deeper, more universal understanding of helminth diagnosis and how to conduct parasitic worm epidemiological surveys.
5 Point Conclusion
- Solid piece of necessary work with the aim of improving diagnostic procedures for this high burden, neglected tropical disease.
- Hookworm eggs exhibit time-dependant decay, unlike Schistosoma mansoni eggs. This can be avoided if samples are kept on ice. However, I would still love to know what the ‘4 distinctive time points’ were that they established – surely this is useful and necessary diagnostic information? Either way, a good general rule of thumb to take away from this would be to store stool samples on ice (if possible, within the sweltering heat of the tropics) and don’t dither about the examination process for accurate diagnosis. Both of the aims of the study I set out at the beginning of this piece, are generally well met.
- Why question the Kato-Katz method and then stick with it without adding more for validity of testing?? A few laboratory procedures could be improved – such as blinded (or double blinded) assessment of outcome, which in this case is faecal egg count.
- The direct results are only relevant to Ivory Coast. However, it paves the way for more in-depth analyses throughout the rest of the tropics / sub-tropics and does provide useful, novel and researched information for the conduction of future surveillance studies.
And perhaps of most interest…..
- The Title is well chosen. It made you read it. It made this article one of the most widely circulated Open Access papers among social networks. The authors even poked some light-hearted fun at it in their conclusion by quotation marking piece of shit as if to say….”yeah, that’s right – we did that!” Great stuff, and it brought a smile to my face. Schistosomiasis and helminth infections in general really are what we define a ‘neglected tropical disease’ and given that many top-level researchers devote their time to addressing this, I can fully understand their desire to share their findings in the hope it inspires more people to rally against this burden of momentous proportions. Good on ‘em.
Thank you for reading my fairly vague analysis on an in-depth analysis of a piece of youknowwhat.
This is sort of an “all in one” miniramble, but nonetheless, let me update you on an eventful week.
At the research unit I’ve been working at this summer for my MSc project – a couple of groups have formed. Namely, a desert club, of which Jackie, a Princeton PhD student, is clearly in-charge of through her relentless dictating of which new Vietnamese desert to indulge in with her co-workers every week. Also, this past weekend saw the assembly of a new entourage – who would brave the disease vessel that is the ‘night sleeper bus’, at the expense of my health, to a coastal city of promised fresh air. After an 11 hour overnight bus journey, our 11 souls, confined to the rear bunks of the shuttle, stepped foot in Nha Trang.
The sea breeze provided fuel for rejuvenation, and Nha Trang – the home to the discoverer of Yersinia pestis (the agent for causing bubonic plague) in a time long ago – provided pure respite from the incessant buzz of motorbikes in Ho Chi Minh City.
Equipped with nothing but each others company (and a couple of snorkles), we swam, speedboated, lounged, laughed, ate, motorbiked (sorry Mum and Dad – won’t happen again), sunbathed, ate, photographed, mudbathed, played cards, ATE, beach partied, walked the coastline, explored an aquarium, and many other things. And of-course – I cannot forget to mention the sheer diversity and deliciousness of the food we had eaten! Sea-food is in the main here and although we sampled a number of restaurants, the real highlight came when we cooked for ourselves and ate together in the comfort of our own rented Villa. Barbecue grilled beef, shrimp and aubergine were courtesy of mine and Uyen’s efforts (a PhD student at OUCRU)…..some yummy noodle dishes thanks to Mi Phan, the mastermind behind the weekend’s excursions….. and a number of other goodies from everyone else in the group.
It has been an absolute pleasure to be part of Oxford University life in Viet Nam this summer – and it’s all going by at an eye-watering rate. My project has been engaging, the academics I’ve met – encouraging, and the new friends I’ve made – brilliant and inspiring. Each of them have their own incredible story to tell, with distinct passions and visions but a combined goal of making advances in science and medicine – in the broadest sense of these terms. One new friend and PhD student from Princeton, Ruthie (who happens to be a former LSHTMer too), is currently on a plane away from Viet Nam. As a mathematical / statistical modeller with a focus on HIV, I know she’s off to make big news, even if it is in humble steps. She’s the first of our Summer researchers to go – and I can’t help but think how grateful I am for the time spent here so far. Good luck Ruthie – we’ll miss you!
And as for New Discoveries – well, let’s just say the ball is rolling in the science park. It looks as if I have discovered three new strains of Bat Coronaviruses in Viet Nam – with all current evidence pointing towards this. Now, this is exciting for a number of reasons…. but on a personal level my thoughts are “bloody hell this is cool!”. Next week I’ll be going to the heart of the forest in which some of these bats belong – It’ll soon be time to embrace the mystery of nature in one of Viet Nam’s most forested areas of land.
For my next few posts (coming soon) – I promise to explain the A to Z of my project, the findings, the implications and the science behind it all.
Settling into a recent Vietnamese breakfast ritual of mine, which I’m swiftly becoming accustomed to, of ‘Pho’ and ‘Bahn My’ accompanied by the beast of an engine starter that is “cà phê sữa đá”, I open up my e-mails to some worrying news. A colleague at the Oxford University Clinical Research Unit – Jackie – had sent me a link to an online update by the BBC on Middle-East Respiratory Syndrome (or MERS for short), a disease caused by a previously unseen coronavirus (prior to late 2012). Coronaviruses are the kind of viruses I’m studying here in Viet Nam. There has been yet another death at the hands of this virus, taking the total death toll of MERS-CoV to to 42. (The article linked is incorrect with their final tally)
This time the victim passed away in a UK hospital. Cases have been confirmed in at least 9 countries but it is believed, after molecular and epidemiological analysis, that this virus originated in the Middle East (as the name would suggest). The virus is particularly harmful to those with underlying health issues and people heading towards the “old age” bracket (or in it!), causing horrendous difficulty in breathing (respiratory illness) as well as fever, malaise and a nasty cough.
The symptoms are similar to SARS, which spawned in the human population in 2002 and took the lives of 775 people. As I mentioned in an earlier post, SARS was also caused by a coronavirus.
But where did it come from?!
We are far less certain about the actual source of the MERS virus. But here’s what we do know – the majority of emerging pathogens come from animals. Are camels the culprit? Or bats again? The popular theory behind the emergence of SARS is that bats such as Rhinolophus sinicus, which were found to harbour viruses with high similarity to the SARS virus, infected animals such as palm civets and racoon dogs. These animals were frequently being penned up in horrific conditions throughout live ‘wet’ markets in Southern China, enabling high frequency of animal and human contact and numerous opportunities for the virus to come into contact with humans. What happened next was the real game changer – the virus adapted to new hosts. US. However, to date we cannot 100% rule out the bats actually had (or have) the direct SARS virus and passed it directly to humans in some cases. It could be out there – we just may not have found it yet.
Maybe a similar story is behind the emergence of MERS-CoV. In fact – we know that two viruses previously identified in bats have the highest similarity to the human MERS-CoV. However, these were identified in Japanese bat populations, and little bat virus surveillance has been done in the Middle East.
It’s clear – we’re missing a tonne of links here. It is an immense challenge to piece it all together, but one we should take seriously if we are to avoid further cases of MERS-CoV infections and more animal to human crossover of infections in the future. It’s all work to prevent the next pandemic.
That’s why I love my project – hunting for these kind of viruses within bat populations of Viet Nam. It’s risky, real and relevant – and I’ll update you on my findings later!
Can a virus make your brain bigger? Well yes – quite literally so when we’re talking about Viral Encephalitis. A couple of case studies I’ve encountered on my journeys pushed me to find out more about this intriguing medical scenario.
Viral encephalitis is a very worrying (clinically speaking) disease manifestation whereby your brain and central nervous system tissues swell up. Other nervous tissue damage can occur too and particularly problematic cases arise when bleeding occurs within the brain, called an ‘intracerebral hemorrhage’. There’s a number of symptoms to watch out for, from ‘light sensitivity’ and fever to partial paralysis and coma! If you’re lucky enough to receive treatment – your odds of survival are significantly improved…..BUT this depends on a number of factors:
Age (particularly those under 12 months and over 55 show the poorest response to treatment)
Immune status. Those with a weakened immune system from HIV or perhaps other causes are often at risk of developing severe encephalitis.
Neurological Health. Say if you’re a stroke survivor – your brain has already done an immense job to recover, but its’ forever more fragile.
AND OF COURSE…..
The virus behind the issue.
But even if treatments work – a survivor may still have neurological problems for the remainder of their life!
Here I am in the Asian tropics, where the Japanese Encephalitis Virus is the don for causing this often life-threatening disease, especially when it is not treated. Now, Japanese Encephalitis Virus (or JEV) is a virus which belongs to the same FAMILY of viruses as Dengue, Yellow Fever and Hepatitis C – the Flaviviridae.
Despite the Latin, I hope I’ve still got a hold of you!
It is quite clear, this family of viruses already has a big reputation for causing severe illnesses. What’s interesting is that another three ‘Flaviviruses’ are able to cause viral encephalitis, albeit much less commonly. Here’s a full list of the main viruses known to cause viral encephalitis in humans:
Tick Borne Encephalitis (TBE)………..(flaviviridae)
West Nile Virus (WNV)………………(flaviviridae)
St. Louis Encephalitis (SLE)………(flaviviridae)
Herpes Simplex Virus-1 (HSV-1, Herpesviridae)
Herpes Simplex Virus-2 (HSV-2, Herpesviridae)
La Crosse Encephalitis (Bunyaviridae)
Varicella Zoster Virus (VZV – Herpesviridae)
Epstein-Barr Virus (EBV – Herpesviridae)
Cytomegalovirus (CMV – Herpesviridae)…often as a result of co-infection with HIV
and some Enteroviruses, such as Coxsackie A
So, quite a few then!
In so called ‘developed’ countries, HSV-1 is the most common inducer of viral encephalitis, with just over 2000 cases per year, to quote USA figures. Here in Asia – JEV has the throne, causing up to 50,000 cases annually. Incredibly, we have a vaccine for JEV – but its pretty pricey, costing £150 from the NHS in the UK. This doesn’t really do the population who are most at risk of contracting JEV many favours, as they’re not so likely to have the means to pay for it.
Nasty disease…What’s the Treatment?
For HSV-1 encephalitis, its acyclovir. This drug is the standard for HSV infections, and generally does the trick to reduce the rate of mortality from 70% to about 30%.
As for Japanese Encephalitis….here’s a story:
I had the honor of shadowing a veteran in Tropical Medicine, in a busy hospital within Ho Chi Minh City recently. He approached one patient in a severe comatose state – scoring 2 on the Glasgow Coma Scale to be precise (http://en.wikipedia.org/wiki/Glasgow_Coma_Scale). The Doctor, deep in thought and concern, turns to me and confirms:
“This patient tested positive, through molecular diagnostics, for Japanese Encephalitis”..
I immediately feel the weight of his words. “What’s the prognosis?” I reply.
“Tough to say. The patient is under treatment with acyclovir, and fortunately, making slow but steady progress.”
My eyebrows raise. Acyclovir!? Acyclovir was specifically designed to combat the Herpesviruses – a completely different genetic construct to the family which JEV belongs to. My naive knee-jerk reaction is to blabber this exact thought….
“Why acyclovir? I thought that was for herpesviruses!?”
The Doctor flashed a knowing smile. “So did I. But we did a clinical trial a few years ago – and it seems to work. Because of those results, its now almost a standard treatment for Japanese Encephalitis here in Viet Nam. Nobody knows exactly why it works though”….
Pleasantly surprised by this fancy info, all I could reply was a monotone “Oh, that’s cool”… when I’m really thinking “Bloody hell that’s amazing. Tell me about the trial. Any guesses as to how it works”….but really – there’s no time, and he moves me onto the next patient who also happened to be suffering from encephalitis, although the root cause of this case has not been confirmed by any diagnostic test.
I’m constantly reminded as to how fragile life is. However, nothing brings it home more than witnessing a fellow human fighting for survival and whose chances ultimately depend on the Doctor’s call and the nature of the beast (the virus) which put them in such a way. We are extremely fragile, but luckily, Scientists and Doctors are taking leaps and making huge advances in health-care all the time. Following their hunch that acyclovir might help treat Japanese Encephalitis is testament to the beauty of daring to take risks to save lives.
Whilst Viral Encephalitis is still a problem globally, causing thousands of deaths per year, let us hope more advances like these can be made to halt this cruel disease.
Maybe. Just maybe. My colleague here at OUCRU has some preliminary results indicating that a hantavirus, most commonly found in rodents and able to cause haemorrhagic diseases (brutal!), is present within the Viet Nam Bat population.
We’ll need clarification. But bloody hell – this is exciting. A hantavirus in a Bat is a RARE find.
I’m two weeks into life in Ho Chi Minh City, Viet Nam. The food, as previously assured by friends who have visited in earlier times, is scrumptious. The heat – just what the Doctor ordered. The air leaves a lot wanting here, if I am honest, but its a big city. What else to expect?
The reason for my touchdown in Viet Nam? I’ve been sent on a mission by LSHTM, the same mission every LSHTM Masters student is currently embarking on, in equally diverse and exciting parts of the World. I’m here to tackle my MSc Project. This counts for 30% of the degree. There’s no doubt – it’s a biggie!
The Oxford University Clinical Research Unit (OUCRU), Ho Chi Minh City, has been kind enough to host my project – and what an atmosphere! A conglomeration of tropical disease experts, epidemiologists, inspired scientists and aspiring students from BSc right through to PhD, all have their integral part to play in the success of OUCRU. To give a sense of the people we’re dealing with here – The director of OUCRU is currently preparing to take over as Director of The Wellcome Trust, in London, UK. That’s arguably the biggest funding body for Medical Research in the UK. I was fortunate to share a lunch banquet with him and shake his hand. It was only brief but the calm eyes and assured smile said it all – at least to me – Great guy.
Elisabeth Pisani is another OUCRU resident. She wrote a book recently titled “The Wisdom of Whores”. I’ve not read it but I know one very special person in my life who has and well…. the reviews are much in line with The Guardian’s take on it.
I’m also fortunate to be mentored by a Heavyweight in the world of science. Dr Juliet Bryant specialises in zoonotic diseases; getting to the bottom of why pathogens in animals cross over into humans and cause disease. We’ve heard about Influenza a lot over the years, H1N1 (swine flu), H5N1 and the recent emergence of H7N9 in China just earlier this year. Influenza has been a mainstay of Dr Bryant’s work.
But do you remember SARS? The disease which emerged in 2002, infected over 8,000 people in 32 countries and had taken the lives of 774 people by July 5th 2003, when it was declared by the World Health Organisation as ‘contained’. You’ve surely heard about MERS, or ‘Middle East Respiratory Syndrome’, which was first identified in a Saudi Arabian man towards the end of 2012 and has gone on to infect at least 64 people and take the lives of 38 to date….no? Well, these diseases are caused by a type of virus called Coronavirus. What IS interesting, is that every indication we currently have on the origin of these viruses, which have caused (and still do) major public health challenges, points towards Bats as the source.
This is what makes the outcomes of my project all the more important. Dr Bryant has recently developed an interest in seeking out what coronaviruses are out there in Vietnamese bat populations (among other viruses). The real excitement comes from the fact that this has NEVER been done before in Viet Nam. There are no publications (at the time of me writing this) declaring the identification of a coronavirus in bats in Viet Nam. There’s tonnes in China, some in Philippines, Thailand and Japan….and even some studies from Mexico. But Viet Nam – not a sausage.
This the excitement of ‘pathogen discovery’ orientated science. The hypothesis: “Coronaviruses are present within bat populations in Viet Nam”.
Because bats appear important in the evolutionary and ecological history of coronaviruses, according to numerous studies. On top of this – virus hunting in bat populations of other countries has often proved fruitful.
I will discuss more about the specifics of my project (the hard-nut science stuff) in a later post, but for now I’ll just outline 3 reasons why this kind of research is of importance to us all (and there’s a bunch of studies to back up my claims….which I’ll happily point you towards)
1. We will get a clearer understanding of coronavirus circulation within bat populations of Viet Nam. Moreover, we may find a previously unidentified coronavirus.
2. Our findings are likely to help build a picture of the potential for zoonotic transmission and understanding drivers for disease emergence (not just of coronaviruses).
3. Viet Nam has suffered heavily from deforestation over the years, affecting bat habitats. Bats are beautiful creatures and are integral to ecological maintenance. A number of studies world over have identified correlations with wildlife habitat loss / disruption and disease emergence. Our findings will add to what is known about the correlations with habitat status and viral zoonoses in Viet Nam.
….So it’s labs daily for me. Tomorrow there’s an academic meeting with an expert in Bat Viruses at OUCRU. Plenty to get excited about. It feels as if I’m continuously blessed as I add to my incredible experiences in Viet Nam. I’ll be posting more about life at OUCRU, Vietnam and Tropical Disease in general.
A shout out to all my LSHTM student colleagues – I hope you are well wherever you are, and you are enjoying your projects too. All the best!