This is the time of year when we reflect on the event of the past year and prepare for what might be coming over the horizon. 2011 was a year of steady progress in the field of infectious diseases, with notable milestones in all of the big three and some game-changing developments for other infections.

The MicroGnome has picked a handful of achievements for this 2011 MicroGnome review that should inspire anyone with an interest in infection. If you have been living under a stone all year, maybe you should try the coffee zone for a less demanding read.

• Malaria: progress made on a malaria vaccine that works

Reporting the preliminary results of a phase three trials of the RTS,S vaccine candidate in neonates and infant groups from seven African countries over 14 months, the authors of a November paper in the New England Journal of Medicine reported a halving of malaria, and a 45% reduction in severe malaria cases. While these effects are far less than routinely used childhood vaccines, they raise hopes for development of a mortality-reducing malaria vaccine.

• Tuberculosis: working out rapid molecular tests for TB in low income countries

Promising early performance studies prompted the World Health Organisation and other donor agencies to equip clinical laboratories in resource-poor countries with rapid molecular screening tests for pulmonary tuberculosis. In a useful review of this application of molecular microbiology, Carlton Evans explains the need for caution in the introduction of this technology to low and middle income countries.

• HIV/AIDS: antiretroviral therapy has a primary preventive effect

There is a growing awareness of the potential for antiretroviral agents in a preventive role. In a mathematical model of the cost effectiveness and impact of different strategies, an international group showed that effective preventive pre-exposure prophylaxis of the uninfected partner could be more effective than commencing ART earlier in the infected partner.

• Septicaemia: MALDI-TOF speeds up bacterial identification in septicaemia

The application of mass spec-based methods for identifying the contents of blood cultures has been gathering pace in Europe for several years, and has started to spread to other parts of the world. While some clinical laboratory directors might have their heads stuck in the sand, there are plenty of pathologists who would give an arm and a leg for equipment that can trim around 24hr or more off the time to identification of bacterial causes of septicaemia. Klein and colleagues are one of many groups working out how to implement this emerging technology in a busy clinical laboratory service.

Influenza: working out why the vaccine had adverse effects

the adverse effects of Australian produced vaccine are thought to have been due to suboptimal virus splitting by a deoxycholate-based procedure. Benefits of vaccination still outweigh the risk of adverse effect.

• Dengue fever: vaccine trials promise improvements in dengue control

A phase three trial of a tetravalent live attenuated vaccine against dengue virus is now under way. Once industrial production of this promising candidate has been established, its efficacy confirmed and administration optimised, it will be of considerable interest to many parts of the tropics where dengue is a substantial burden on the public health.

So what’s in store for 2012, apart from more of the same?

At a guess, it looks like we’re going to drill deeper into severe sepsis, see an expanding series of field studies and continue our peripatetic investigation of tropical infectious diseases. The language of infection series is set for significant expansion in support of teaching and training activities. One outcome of our 2011 MicroGnome Review was to recognise the need for an expanded writing team. The group sends you their best for 2012, and will now pause briefly to welcome in the New Year.

The 2011 influenza vaccine campaign gets off to a slow start.

Adverse effects of the 2010 vaccine may be to blame.

It is now exactly a year ago that the flu vaccine was withdrawn for children in Western Australia. The reason was the hospital admission of around 45 children with fever and convulsions after vaccine administration.  A detailed investigation implicated a specific brand of flu vaccine made by CSL and known as Fluvax. Other types of flu vaccine used last year were not associated with these effects.

This year influenza cases continued to trickle through during the summer months, partly due to international travel. The H1N1/09 strain responsible for the 2009 pandemic is now one of the predominant types of virus and has been targeted by vaccine manufacturers. The virus is responsible for a wide spectrum of disease from minimal effects to life-threatening respiratory or multisystems failure.

Unfortunately, critics have seized on the paediatric problems attributed to a specific vaccine batch as grounds for general criticism of this year’s vaccination programme. Add that to more general skepticism about the risk from influenza virus and you find a powerful explanation for the low uptake of this year’s vaccine. There are concerns the vaccine is being avoided by many for no good reason.

But note: there have been deaths from H1N1 influenza in Australia this year even before the start of the usual infection season. That includes young adults. Public health authorities are now doing their level best to counter the anti-vaccine propaganda and promote influenza vaccination of at-risk children. If it were a simple matter of adults making informed decisions about their own level of exposure to a remote risk, it might be understandable. However, the black-and-white simplicities painted by the anti-vaccination lobby are a parody of infectious disease reality.

• Influenza kills some of the most vulnerable, defenceless individuals in our community every winter.
• Hospital and clinic workers have a particular responsibility to protect the patients they care for by reducing any risk of passing on influenza at work by seeking personal vaccination.
• The most vulnerable who have genuine medical reasons for missing out on the flu vaccine are best protected by vaccinating those closest to them.
• Those with a fear of needles can now get their vaccine in a device that only just penetrates the skin, already shown to produce an improved immune reaction.

Winter is on the way; it’s time to get shot up.

It’s that time of year when all are on the move, and most have caught a bad dose of LETICE (Leave Early Today Is Christmas Eve). We hear it’s been so bad this year with the run-up to a four day holiday that government departments have been granting special LETICE Leave. This could be made a lot worse if there are outbreaks of RELATED (REturn Late After The End of December) disease.

The MicroGnome is glad to report that all those who were travelling away from gnome have safely reached their intended destinations. Whether or not you believe in climate change, Father Christmas or other explanations for global catastrophe, southerners have had to skirt floods while travelling north and northerners have had to brave ice and snow while travelling south. Both contingents may have to grapple with seasonal infections of greater importance than LETICE or RELATED disease. The northern winter is a great time for respiratory infections and particularly pandemic influenza (H1N1/09), which can cause severe pneumonitis or set the scene for a secondary staphylococcal pneumonia. The corresponding period in northern Australia is the wet season when melioidosis peaks. This year should be a big season thanks to floods and a high level of cyclone activity.

• Western Australia
• Northern Territory
• Queensland
• New South Wales

With those sober thoughts, we wish you all a Happy Christmas and look forward to your comments in our second year of blogging.

The MicroGnome.

It’s been a bit quiet lately for students of micrognomics. You didn’t realise how much you missed the micrognome, did you? Here’s a  clue what the micrognome has been up to lately. See if you can work it out from the title. Suffice it to say that he’s been out and about bug hunting.

Forthcoming posts include:

• FACTM part 1 exam news
• Wilderness & Expedition Medicine conference report
• Influenza update
• Another chapter in the Language of Infection
• Microbial genomes news
• More field applications of molecular microbiology

This should keep the Micrognome busy until the end of the year.

All shot up: the flu vaccine controversy

The hot topic right now is what to do about childhood vaccination against epidemic influenza, following the series of apparent adverse reaction to influenza vaccine in pre-schoolers. Already there has been a lot of heat, plenty of noise but not a lot of light on the issue. It is frustrating for all concerned. Not only for the parents of children who’ve had rash, fever or even a febrile convulsion. It is also frustrating for responsible health professionals who’ve advocated an expanded influenza vaccination programme on the basis of hard-won statistical evidence in order to reduce the risk of influenza complications in the most vulnerable. An early evaluation appeared to indicate that the H1N1/09 specific vaccine would be safe in children, though a more recent report indicated a higher rate of mild to moderate adverse reactions in children. Earlier this year there was an impression that there had been a disappointing uptake of pandemic flu vaccine after the winter epidemic of 2009. This was suprising given the severity of disease in specific adult groups, some of whom required admission to intensive care.

In the few days since this issue first arose a series of possible explanations have been offered for the series of apparent vaccine reactions in paediatric patients. These include an immune memory response in children who had already been exposed during last year’s flu season,  a particular batch of vaccine, vaccine potentiation by a second and possibly unrelated viral infection, an abnormally exaggerated vaccine response, or a combination of more than one of these.

Teasing out the various strands of possible cause and effect is a complicated process under the best of conditions. The nature of the public debate means that the health detective work that needs to proceed urgently and methodically risks being diverted by critics who hold to a more general anti-vaccine agenda. Expert opinion, given with the best of intentions is currently in danger of being used out of context to support an unscientific, 19^th century view of vaccination.

Readers of this Blog are reminded that it takes a sizeable body of evidence to pin the blame on a specific microbe as both sufficient and necessary cause of a given disease outcome, even if the microbe has been administered deliberately by needle.

There are four key evidentiary stages to nailing the microbial culprit;

1. congruence
2. consistency
3. cumulative dissonance
4. curtailment

How these operate can be found in the original paper. In outline, the clinical and pathological features of individual cases, the epidemiology and the molecular biology must add up. But that just get’s you to first base. There must also be consistency, a mechanistic explanation for how the microbe exerts its effects, and finally a demonstration of the effect of one or more specific interventions to curtail the infective process.

Application of this evidence-building exercise to the current alleged vaccine reactions at the present time illustrates (a)  the strength of evidence for a causal relationship, and (b) helps identify priorities for further investigation, without losing sight of the need to continue vaccination of vulnerable adults in groups who have yet to show any adverse effects of the current influenza vaccine.

These comments are subject to the caveat at the bottom of the MicroGnome website’s homepage.

Beneath Hill 60, for details click link below

While at high school, the μGnome spent cold autumn afternoons scrambling around in the mud on a rugby pitch. Every now and again we’d be send off by the busload to battle with other schools on their muddy pitches. One away match was particularly memorable. The year before that school had posted a monumental winning score by the simple method of putting one of their best sprinters out on the wing. Our job was to reduce their score by bringing the winger down before he reached the try line, and the best way to do that was with a classic rugby tackle. Not a good way to keep the rugby strip clean. Time and again we put ourselves in the line of fire, throwing bony adolescent shoulders at shins and burying our faces in the increasingly slimy mud. We didn’t win the match, but we cut the score against us to less than half the previous year’s. We felt like heroes.

War memorial

Outside the main school building was an impressive war memorial; a large bronze of a former pupil collapsing on a battlefield and shouting the one word ‘Onward!’ with his dying breath. As pupils from another school, we were told the cautionary and probably apocryphal tale of an ill-advised student who’d been expelled for putting a peeled orange in the upturned hand of the bronze FP. The sacrifices made by that generation are not a joking matter, and it is a sobering thought that the same college describes its school colours as ‘mud and blood’.

Messines Ridge

The mud and blood of the Western Front have been superbly depicted in Jeremy Sims recent movie, Beneath Hill 60. This feature length film is a powerful visual essay on the futility of industrial-scale trench warfare. It tells the story of the 1st Australian Tunnelers; a unit formed to excavate underneath the enemy lines. The film has a narrative integrity that leaves few if any hostages to the crass jingoism of that age, and yet it successfully portrays how individuals got swept up by the tide of events and sucked into their grip. This is a movie about heroes. It says most about the small acts of heroism that maybe don’t even rate a mention in despatches. It also throws open a window on the consequences of decisions that individual soldiers have to make in the heat of battle. [see also BBC post on trench warfare sites]

Infection in the trenches

There is another encounter with battlefield mud that gets little mention in Beneath Hill 60; the infections troops suffered as a result of trench warfare. There were infections other than influenza (whose effect was so great the 1918-19 pandemic may have alterered the course of the final stages of WW1) that commonly befell the men who huddled in trenches against shell and machine gun fire. These included trench fever, a louse-borne disease caused by Bartonella quintana; Leptospirosis and gas gangrene. Interestingly, the tropical soil-borne disease known as melioidosis is endemic in the area around Townsville, where filming was done for Beneath Hill 60. In fact, the 6th World Melioidosis Congress will be held there later this year. The μGnome wonders whether any of the actors have been exposed to Burkholderia pseudomallei, the bacteria that cause melioidosis, as a result of encounters with mud and blood on the film set in North Queensland.

ANZAC memorial

Today, April 25th, is ANZAC Day in Australia and New Zealand; the 95th anniversary of the fateful Gallipoli landings. Tragic failure though the landings proved to be, this day is now an opportunity to remember those in the armed services of both countries who held the door shut against the enemy outside. It is a day to remember those who have given much, sometimes all, in the service of others, including those who continue to put their personal safety on the line to preserve the life most of us enjoy in peace, quiet and relative obscurity. Some are critical of the semi-religious tone to this time of reflection and memory, but as Stephen Ambrose documented in his account of one US soldier’s experience during the fierce fighting at Bastogne during 1944, “there are few atheists in foxholes”. Extreme challenges make us all dig deep, and not just to the bottom of the foxhole.

Marking their legacy

For those who want to do something practical as a mark of remembrance, you can make a donation to Legacy who provide support to the families of former diggers. And for those who specifically want to direct their generosity overseas, Australian communities are twinning with towns and villages in East Timor to assist their development and reconstruction. This ANZAC Day, the ABC will run a documentary on the support East Timor gave Australians during World War 2; reason enough to repay that generosity through the appeals Australian communities are now running.

Family ties

Today is also the day many remember overseas friends and relatives who were caught up in both world wars and smaller conflicts. In my own family, parental and grandparental generations fought in Europe. Those from my grandfather’s generation who survived the rigors of trench warfare during the First World War, were pressed into service at the start of the Second World War. Having survived his first two weeks as a subaltern, raids into no-mans-land, poison gas and a plane crash during WW1, he joined up in 1938 and stayed behind in northern France with elements of the 51st Highland Division as part of the rearguard action that continued until their final surrender at St Valery (after the Dunkirk evacuation). The action near Escarbotin lasted little more than three days and was an increasingly desperate affair with an inevitable conclusion. He spent the remainder of WW2 in POW camp. Decorations for distinguished service seem a small token of gratitude for a gritty determination not to cave in to pressure from a much stronger enemy. But aside from military calculations of risk, benefit, gain and loss is the human dimension of extreme conditions in which deep friendships are forged, even if life-long turns out to be a matter of hours or days. Grandfather noted in his first footnote to the submission for the official regimental history that “the action was conducted without the pipes” [bagpipes]. It’s a matter of perspective. Beneath Hill 60 captures those moments of jocular, men-in-a-trench humour rather well.

CAPT JD Inglis, DSO, MC & Bar (1901-1975)